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Abstract Objective To investigate the effect of the flexion angle of a femoral prosthesis on the postoperative clinical outcome of patients with knee osteoarthritis who are undergoing unicompartmental knee arthroplasty. Methods Patients were divided into three groups according to the flexion angle of the femoral prosthesis following unicompartmental knee arthroplasty. Group A comprised patients with a flexion angle of the femur prosthesis of less than 5°, Group B included those with a flexion angle of 5° to 10°, and Group C consisted of patients with a flexion angle of the femur prosthesis greater than 10°. The basic clinical data, visual analog scale (VAS) score, Hospital for Special Surgery (HSS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and knee range of motion (ROM) were subjected to statistical analysis and comparison between the groups. Results No significant differences were observed in the basic data of the patients in each group. The ROM and VAS scores for the knee in the first month following unicompartmental knee arthroplasty in groups B and C were significantly greater than those in group A. The HSS scores for the knee joint in Group B indicated superior outcomes in the initial postoperative month and the third postoperative month, as evidenced by the WOMAC scores, which demonstrated a statistically significant difference between Group B and the other two groups within the six-month postoperative period. Conclusion The short-term recovery of patients in Group B was the fastest. These results provide a new reference for the installation of femoral prostheses in unicompartmental knee arthroplasty.

Abstract Background This study aimed to compare the impact of olanzapine, magnesium valproate, and lamotrigine as adjunctive treatments for anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. And it is expected to add supporting points related to the rebalance of neurotransmitters in the brain through adjuvant therapy in the clinical management of anti-NMDAR encephalitis. Methods This retrospective study included patients diagnosed with anti-NMDAR encephalitis who received standardized immunotherapy at Hunan Brain Hospital between January 2018 and December 2020. Results Compared to the olanzapine group, both the magnesium valproate and lamotrigine groups showed lower scores on the positive and negative symptom scale (PANSS) total score after 3 weeks of treatment (all P 0.05). Conclusion Compared with olanzapine, the addition of magnesium valproate or lamotrigine to immunotherapy might be associated with a lower PANSS score, higher MoCA score, and lower mRS score. The improvement of neurological functions and cognitive function may be related to the decreased Glx/Cr ratio.

Abstract The global water crisis demands immediate attention, and atmospheric water harvesting (AWH) provides a viable alternative. However, studying the real‐time subtle relationship between water absorption, diffusion, and internal structure for hygroscopic materials is challenging. Herein, a dynamic visualization technique is proposed that utilizes an in situ electrical impedance tomography (EIT) system and a precise reconstruction algorithm to achieve real‐time monitoring of the water sorption process within aerogels from an internal microstructural perspective. These results can be inferred that composites' pore sizes affecting the kinetics of their moisture absorption. In addition, the diffusion path of moisture absorption and the distribution of stored moisture inside aerogels exhibit intrinsic self‐selective behavior, where the fiber skeleton of the aerogel plays a crucial role. In summary, this work proposes a generic EIT‐based technique for the in situ and dynamic monitoring of the hygroscopic process, pointing to an entirely new approach regarding research on AWH materials.

Due to the rise in gas prices and the surge in greenhouse gas emissions, individuals have turned to various renewable energy options. Silica aerogels are highly effective to maintain either hot or cold Temps. Insulation options with proficient thermal storage capabilities, such as phase change materials (PCMs), are highly beneficial. This study aimed to determine how the size of copper oxide nanoparticles affected the behavior of a silica aerogel/paraffin nanostructure within a duct. The researchers utilized computer simulation as a means to examine the thermal behavior (TB) and complex properties of the particles. To accomplish this objective, we evaluated the effect of various factors, such as the size of NPs incorporated into the structure, on density, temperature (Temp), heat flux, thermal conductivity, and charging and discharging time. According to the results, by increasing the radius of the nanoparticle to 10 Å, the density value in the atomic sample reached 0.1353 atoms/Å3. Moreover, the velocity (Vel) decreased to 0.0085 Å/fs. As the radius was 10 A, the thermal conductivity decreases from 1.74 W/m.k to 1.65 W/m.K. Also, by increasing the size of the nanoparticle, the charging and discharging time in the target atomic sample increases and decreases to 6.28 ns and 8.52 ns, respectively.

Abstract Since ancient times, humans have learned to use fire and other heating methods to fight against dangerous pathogens, like cooking raw food, sterilizing surgical tools, and disinfecting other pathogen transmission media. However, it remains difficult for current heating methods to achieve extremely fast and highly efficient sterilization simultaneously. Herein, an ultrafast and uniform heating‐based strategy with outstanding bactericidal performance is proposed. Ultra‐precise laser manufacturing is used to fabricate the Joule heater which can be rapidly heated to 90 °C in 5 s with less than 1 °C fluctuation in a large area by real‐time temperature feedback control. An over 98% bactericidal efficiency on S. aureus for 30 s and on E. coli for merely 5 s is shown. The heating strategy shows a 360 times faster acceleration compared to the commonly used steam sterilization from the suggested guidelines by the Centers for Disease Control and Prevention (CDC), indicating that high temperatures with short duration can effectively disinfect microorganisms. As a proof of concept, this heating strategy can be widely applied to sterilizing cash and various objects to help protect the public from bacteria in daily life.

Abstract Activated microglia have been implicated in the pathogenesis of age-related macular degeneration (AMD), diabetic retinopathy, and other neurodegenerative and neuroinflammatory disorders, but our understanding of the mechanisms behind their activation is in infant stages. With the goal of identifying novel genes associated with microglial activation in the retina, we applied a semiquantitative fundus spot scoring scale to an unbiased, state-of-the-science mouse forward genetics pipeline. A mutation in the gene encoding the E3 ubiquitin ligase Herc3 led to prominent accumulation of fundus spots. CRISPR mutagenesis was used to generate Herc3 -/- mice, which developed prominent accumulation of fundus spots and corresponding activated Iba1 + /CD16 + subretinal microglia, retinal thinning on OCT and histology, and functional deficits by Optomotory and electrophysiology. Bulk RNA sequencing identified activation of inflammatory pathways and differentially expressed genes involved in the modulation of microglial activation. Thus, despite the known expression of multiple E3 ubiquitin ligases in the retina, we identified a non-redundant role for Herc3 in retinal homeostasis. Our findings are significant given that a dysregulated ubiquitin–proteasome system (UPS) is important in prevalent retinal diseases, in which activated microglia appear to play a role. This association between Herc3 deficiency, retinal microglial activation and retinal degeneration merits further study.

Background: We present the conceptual framework, design, and study measures of Nurturing Healthy Teachers, a quasi-experimental study to examine the short- and long-term effectiveness of the Nurturing Healthy Teachers (NHT) nutrition intervention on food insecurity, dietary behaviors, mental health and cardiometabolic health among preschool and elementary school teachers. Methods: A convenience sample of 28 elementary schools with pre-kindergarten and elementary classrooms were recruited in Houston, Texas. Nurturing Healthy Teacher intervention includes Brighter Bites, an evidence-based coordinated school health program that combines access to fresh produce and nutrition education, and Create Healthy Futures, a web-based nutrition education program that targets nutrition knowledge, self-efficacy, mindfulness, and social support to create healthy habits among teachers. The primary outcome is food insecurity. Secondary outcomes include diet quality, mental health, and cardiometabolic health. Metabolic markers and skin carotenoid levels were assessed using in-person assessments, while all other measures were obtained via questionnaire. Results: At baseline, most of the participants were female, 63 % identified as Hispanic, were highly educated, and had a mean age of 42.6 years. Overall, 50 % of teachers were classified as being obese and 20 % had high cholesterol. At baseline teachers had a mean HbA1c (%) of 5.6 %. Moderate to severe depression was experienced by 18 % of teachers and 23 % of teachers experienced moderate to severe anxiety. Conclusions: The results of this study will inform next steps towards future implementation and evaluation of teacher-focused interventions.

The South-to-North Water Diversion Project in China is the world’s largest water transfer project, aiming to address water shortages in northern China by channeling water from the water-rich southern regions. Water resources in Tianjin have long been in severe deficit, with excessive groundwater extraction causing significant surface subsidence, negatively impacting urban infrastructure and economic development. As a result, Tianjin has become a key beneficiary of this water diversion project. To investigate the current situation of surface subsidence, we obtained the vertical displacement time series from 21 GNSS stations across Tianjin from 2011 to 2021 and analyzed overall subsidence changes and rehabilitation status. Results indicate that no clear surface subsidence was observed in the northern regions of Tianjin due to groundwater extraction mainly in unconfined aquifers. The southwestern region experienced the most significant surface subsidence due to overexploitation of deep groundwater, with peak cumulative subsidence exceeding 600 mm during the study period. The central, eastern, and southeastern coastal regions also faced severe surface subsidence with cumulative amounts ranging from 100 mm to 400 mm. The alleviation of subsidence predominantly benefits from continuous water supply from the South to North Water Diversion Project, which resulted in most stations significantly slowing down or even stabilizing their settlement rates after 2018. Therefore, the South-to-North Water Diversion Project plays a crucial role in addressing the persistent water resource shortage and mitigating long-term surface subsidence in Tianjin by ensuring a continuous water supply and significantly reducing the need for groundwater extraction. Our findings indicate positive measures, such as water diversion projects and water management policies, can serve as valuable references for other regions around the world facing similar water scarcity and groundwater overexploitation.

Abstract Breast cancer can metastasize to various organs, including the lungs. The immune microenvironment of the organs to be metastasized plays a crucial role in the metastasis of breast cancer. Infection with pathogens such as viruses and bacteria can alter the immune status of the lung. However, the effect of chronic inflammation caused by bacteria on the formation of a premetastatic niche within the lung is unclear, and the contribution of specific immune mediators to tumor metastasis also remains largely undetermined. Here, we used a mouse model revealing that chronic pulmonary bacterial infection augmented breast cancer lung metastasis by recruiting a distinct subtype of tumor-infiltrating MHCIIhi neutrophils into the lung, which exhibit cancer-promoting properties. Functionally, MHCIIhi neutrophils enhanced the lung metastasis of breast cancer in a cell-intrinsic manner. Furthermore, we identified CCL2 from lung tissues as an important environmental signal to recruit and maintain MHCIIhi neutrophils. Our findings clearly link bacterial-immune crosstalk to breast cancer lung metastasis and define MHCIIhi neutrophils as the principal mediator between chronic infection and tumor metastasis.

In industrial environments where combustion (Com.) is widely carried out, such as steam power plants, gas turbines, etc., the most common way to express the amount of oxygen consumption is its excess percentage in addition to the stoichiometric ratio, and the nearness of a catalyst causes combustion to happen at a high ratio. There are different influential factors in catalytic combustion, such as initial temperature (IT). The current study uses the molecular dynamics (MD) method to examine how the IT and oxygen ratio affect air-methane catalytic combustion in a helical microchannel. The LAMMPS package was used to conduct this investigation. This study examines how simulated structures function during burning in excess oxygen (EO) and oxygen deficiency (OD). Furthermore, palladium was used as a catalyst with an atomic ratio of 4 %. The findings show that raising the IT may enhance its atomic behavior (AB) and thermal performance (TP). The maximum velocity (MV) and maximum temperature (MT) increased from 0.26 Å/ps and 1617 K to 0.45 Å/ps and 1891 K in EO as IT increased from 300 to 700 K. By accelerating the particle velocity, it is anticipated that the catalytic combustion process would proceed more quickly. As a result, after increasing the IT to 700 K, the heat flux (HF), thermal conductivity (TC), and combustion efficiency (CE) increase to 2101 W/m2, 1.23 W/m. K, and 93 %, respectively. On the other hand, the results show that increasing IT affects combustion performance in the presence of OD. In the presence of OD, the MV and CE converge to 0.38 Å/ps and 94 % at 700 K. Therefore. It can be concluded that the atomic ratio of oxygen and the IT can significantly affect combustion process.

AbstractIn the therapy of placenta-originated diseases during pregnancy, the main challenges are fetal exposure to drugs, which can pass through the placenta and cause safety concerns for fetal development. The design of placenta-resident drug delivery system is an advantageous method to minimize fetal exposure as well as reduce adverse maternal off-target effects. By utilizing the placenta as a biological barrier, the placenta-resident nanodrugs could be trapped in the local placenta to concentrate on the treatment of this abnormal originated tissue. Therefore, the success of such systems largely depends on the placental retention capacity. This paper expounds on the transport mechanism of nanodrugs in the placenta, analyzes the factors that affect the placental retention of nanodrugs, and summarizes the advantages and concerns of current nanoplatforms in the treatment of placenta-originated diseases. In general, this review aims to provide a theoretical basis for the construction of placenta-resident drug delivery systems, which will potentially enable safe and efficient clinical treatment for placenta-originated diseases in the future.

Abstract Microglia play a role in the pathogenesis of many retinal diseases. Fundus spots in mice often correlate with the accumulation of activated subretinal microglia. Here we use a semiquantitative fundus spot scoring scale in combination with an unbiased, state-of-the-science forward genetics pipeline to identify causative associations between chemically induced mutations and fundus spot phenotypes. Among several associations, we focus on a missense mutation in Lipe linked to an increase in yellow fundus spots in C57BL/6J mice. Lipe −/− mice generated using CRISPR-Cas9 technology are found to develop accumulation of subretinal microglia, a retinal degeneration with decreased visual function, and an abnormal retinal lipid profile. We establish an indispensable role of Lipe in retinal/RPE lipid homeostasis and retinal health. Further studies using this new model will be aimed at determining how lipid dysregulation results in the activation of subretinal microglia and whether these microglia also play a role in the subsequent retinal degeneration.

Based on conventional observation data, regional station observation data, EC reanalysis data, FY-2G satellite data, and radar data, a downburst in Yichang on 29 July 2017 was analyzed. The results show that: (1) The downburst occurred at the edge of subtropical high, the convection in the north of Yichang was triggered by cold air, and the convection in the central section was triggered by the uplift of mountain terrain in the west of Yichang. (2) the downburst was accompanied by the abrupt rise of air pressure, the sudden drop in air temperature, the sudden change of wind direction, and the sudden increase of wind speed. The strong and rapid cold outflow has the most obvious influence on the occurrence of the gale. (3) Satellite cloud image shows that the location of gale is basically in the area with the largest cloud top brightness temperature gradient in the front of cloud cluster propagation direction. (4) The process is characterized by a typical pulse storm and the initial thunderstorm. The echo intensity is strong, the height is 4~6 km, the echo shape is vertical, and there are obvious radial convergence characteristics in the middle layer about 10 minutes before the surface gale appears. (5) The echo is strengthened twice in the process of moving and developing, one is echo merging enhancement and the other one is strengthened by local thermal and dynamic convergence near the Three Gorges Dam Area, and blocked by the Yangtze River Valley twice and the high blocking effect. The echo moves slowly in the Yangtze River Valley, so it can last for a long time.

Abstract Glioma, the most common of malignant tumors in the brain, is responsible for the majority of deaths from primary brain tumors. The regulation of long noncoding RNAs (lncRNAs) in HIF‐1α‐driven tumor development remains unclear. LINC02774 is a nuclear lncRNA and that it is being reported for the first time in this study. We found the downregulation of LINC02774 in glioma and decreased with the degree of malignant, with its expression showing a negative correlation with the relative index of enhanced magnetic resonance (RIEMR). RIEMR‐associated LINC02774 was found to inhibit glycolysis by modulating the hypoxia pathway rather than the hypoxia response itself. LINC02774 interacted with its neighboring gene, RP58 (ZBTB18), to enhance the expression of PHD3, which catalyzed HIF‐1α hydroxylase and ubiquitination, leading to the downregulation of HIF‐1α expression. We also found that the function of LINC02774, dependent on PHD3, was diminished upon RP58 depletion. Notably, higher expression of RIEMR‐associated LINC02774 was associated with a favorable prognosis. In conclusion, these findings reveal the role of RIEMR‐associated LINC02774, which relies on its neighbor gene, RP58, to regulate the hypoxia pathway as a novel tumor suppressor, suggesting its potential to be a prognostic marker and a molecular target for the therapy of glioma.

Context Paclitaxel (PTX) leads to chemotherapy brain (chemo-brain) which is characterised by cognitive impairment. It has been reported that necroptosis is associated with cognitive impairment in some neurodegenerative diseases, but it is not clear whether it is related to the development of chemo-brain.Objective To investigate the role of necroptosis and related changes in PTX-induced cognitive impairment.Materials and methods C57bl/6n mice were randomly divided into five groups: control, vehicle, and different concentrations of PTX (6, 8, 10 mg/kg). Two additional groups received pre-treatment with Gdcl3 or PBS through Intracerebroventricular (ICV) injection before PTX-treatment. Cognitive function, necroptosis, synaptic plasticity and microglia polarisation were analysed.Results PTX (10 mg/kg) induced significant cognitive impairment, accompanied by changes in synaptic plasticity, including decreased density of PSD95 (0.65-fold), BDNF (0.44-fold) and dendritic spines (0.57-fold). PTX induced necroptosis of 53.41% (RIP3) and 61.91% (MLKL) in hippocampal neurons, with high expression of RIP3 (1.58-fold) compared with the control group. MLKL (1.87-fold) exhibited the same trend, reaching a peak on the 14th day. The increased expression of iNOS (1.63-fold) and inflammatory factors such as TNF-α (1.85-fold) and IL-β (1.89-fold) compared to the control group suggests that M1 polarisation of microglia is involved in the process of cognitive impairment. Pre-treatment with Gdcl3 effectively reduced the number of microglia (0.50-fold), inhibited the release of TNF-α (0.73-fold) and IL-β (0.56-fold), and improved cognitive impairment.Conclusion We established a stable animal model of PTX-induced cognitive impairment and explored the underlying pathophysiological mechanism. These findings can guide the future treatment of chemo-brain.

Study region: Southwest China. Study focus: Terrestrial water storage (TWS) changes estimated from the Global Navigation Satellite System (GNSS) and Gravity Recovery and Climate Experiment missions (GRACE/GRACE-FO) are critical data sets for hydrological studies. To obtain a broader and unified spatiotemporal scale than a single method, we designed two improved joint inversion methods (JIMs). The joint inversion method 1 and 2 (JIM1 and JIM2) are based on GRACE/GRACE-FO-derived virtual stations and 3-degree mascons from Jet Propulsion Laboratory, respectively. We focused on investigating TWS changes in Southwest China using JIM1 and JIM2 New hydrological insight for the region: The synthetic test showed that JIM1 and JIM2 had lower root-mean-square-errors than a GNSS-Only inversion method (GNSS-IM), with reductions of 22% and 37%, respectively, confirming their feasibility. The results of JIMs using actual GNSS and GRACE/GRACE-FO data showed that the area-averaged JIMs-TWS estimates were consistent with GRACE/GRACE-FO-TWS and GNSS-IM-TWS, but JIM2-TWS was overfit to GNSS-IM-TWS. Then, we utilized JIM1-TWS to investigate hydro-climate relationships and quantify drought events. The results revealed a strong agreement between JIM1-dTWS/dt and precipitation-evapotranspiration-runoff with a correlation coefficient of 0.89. Precipitation contributed the most to TWS changes. Furthermore, three hydrological drought events were detected, with the third event being the most severe, lasting for 20 months, resulting in a total TWS loss of − 501 km3, and being categorized as an exceptional drought.

Pseudomonas aeruginosa (P. aeruginosa) can cause severe acute infections, including pneumonia and sepsis, and cause chronic infections, commonly in patients with structural respiratory diseases. However, the molecular and pathophysiological mechanisms of P. aeruginosa respiratory infection are largely unknown. Here, we performed assays for transposase-accessible chromatin using sequencing (ATAC-seq), transcriptomics, and quantitative mass spectrometry-based proteomics and ubiquitin-proteomics in P. aeruginosa-infected lung tissues for multi-omics analysis, while ATAC-seq and transcriptomics were also examined in P. aeruginosa-infected mouse macrophages. To identify the pivotal factors that are involved in host immune defense, we integrated chromatin accessibility and gene expression to investigate molecular changes in P. aeruginosa-infected lung tissues combined with proteomics and ubiquitin-proteomics. Our multi-omics investigation discovered a significant concordance for innate immunological and inflammatory responses following P. aeruginosa infection between hosts and alveolar macrophages. Furthermore, we discovered that multi-omics changes in pioneer factors Stat1 and Stat3 play a crucial role in the immunological regulation of P. aeruginosa infection and that their downstream molecules (e.g., Fas) may be implicated in both immunosuppressive and inflammation-promoting processes. Taken together, these findings indicate that transcription factors and their downstream signaling molecules play a critical role in the mobilization and rebalancing of the host immune response against P. aeruginosa infection and may serve as potential targets for bacterial infections and inflammatory diseases, providing insights and resources for omics analyses.

ABSTRACT Purpose: To explore effect and mechanism of olsalazine of Chinese generic drugs on ulcerative colitis induced by dextran sulfate sodium salt (DSS) in BALB/c mice. Methods: The mouse model of ulcerative colitis was induced by free drinking of 3% (w/v) DSS aqueous solution for seven days. The mice were treated with olsalazine (0.6 g·kg-1) of Chinese generic drugs. The therapeutic effect of olsalazine on ulcerative colitis mice was evaluated by measuring disease activity index (DAI), colonic mucosal injury index (CMDI), histopathological score (HS), and detected the expression levels of interleukin (IL)-2, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-1β in serum and IL-7, IL-17, IL-22, epidermal growth factor (EGF), transforming growth factor β1 (TGF-β1) in colonic homogenate of mice. Results: Olsalazine significantly increased the contents of IL-2, IL-10, IL-22, TGF and EGF in ulcerative colitis rats, and significantly decreased the scores of DAI, CMDI, HS and the contents in IL-7, IL-17, TNF-α, IL-1β and IFN-γ when compared with the model group. It improved the degree of colonic lesion in ulcerative colitis mice. Conclusions: It was suggested that olsalazine has a therapeutic effect on ulcerative colitis induced by DSS in mice, and the mechanism may be related to the increase of IL-2, IL-10, IL-22, TGF, and EGF and the decrease of the expression of IL-7, IL-17, TNF-α, IL-1β, and IFN-γ.

Abstract Background Glioma is the most common malignant tumor of the central nervous system and is associated with a poor prognosis. This study aimed to explore the function of growth factor receptor-bound protein 10(GRB 10) in glioma. Methods The expression of GRB10 in glioma was determined based on the glioma transcriptome profile downloaded from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO) databases. RT-qPCR was performed to detect the expression of GRB10 in tissue samples obtained from 68 glioma patients. The patients were followed up via telephone or in-person outpatient visits to determine survival. Kaplan-Meier survival analyses were used to evaluate the effect of GRB10 on the prognosis of glioma patients. Further, we constructed GRB10 knockdown cell lines were constructed to investigate the effect of GRB10 on glioma. The cell growth, colony formation, cell cycle assay, EdU assay, and tumor formation in xenograft were performed. Results The expression level of GRB10 was positively correlated to the histological grades of gliomas. In addition, Kaplan-Meier survival curves revealed that glioma patients with lower expression of GRB10 had more prolonged survival. The knockdown of GRB10 was shown to inhibit cell proliferation, colony formation, and tumor formation in the xenograft models. Cell cycle assay revealed that the knockdown of GRB10 can inhibit the cells entering the G2/M phase from the S phase. The analysis of GSEA suggests that the expression of GRB10 was positively correlated with the hypoxia and EMT signaling pathway. Conclusions Our data revealed that GRB10 regulated tumorigenesis in glioma and played a vital role in promoting the glioma progression, which indicated that GRB10 could be used as a potential prognostic marker.

Obesity is a major risk factor for fatty liver disease. Here, using a forward genetic screen, the authors identify the gene GM4951 as a GTPase involved in lipid oxidation and development of NAFLD in mice.

Mesozoic orogenic gold deposits in the Jiaojia goldfield, Eastern China show the features of regular mineralization spatial distribution and have long been captivated the attention of geologists. This study integrates 3D modeling, model space analysis, and association rule analysis to extract the relationship between structural deformation and gold mineralization. The Apriori algorithm with spatial constraints is used to quantify the favorable mineralization sites in the Jiaojia gold field using different combinations of ore-controlling indicators. The first favorable mineralization site has a 44% probability of mineralization and is primarily located in segments of the fault footwall within 25 m of the fault buffer where the transition from steep to gentle occurs (∼1–24). Its uniform distribution indicates that the ore-bearing space near the main fault plane is relatively wide, and hydrothermal diffusion is relatively uniform. Site No. 2 has a 45% probability of mineralization and is located in convex segments (6–35 m) between 25 and 55 m of the fault footwall. The equidistant zonal distribution in this area indicates that secondary faults and fractures have facilitated the migration of hydrothermal fluids, resulting in the formation of extensive ore-bearing spaces. Site No. 3 sited in convex segments (∼0–6 m) distal to the fault footwall (∼55–515 m) of the fault buffer where the dip is gentle (∼30°–35°). The binary structure of differing dips formed by the intersection of steeply dipping orebodies and the slowly dipping orebodies in the central and southern parts of the Nanlü-Xinmu deposit exhibit the complex channel away from the main fault. In this study, the correlation between ore-controlling factors and mineralization in Jiaojia fold field is quantitatively expressed as favorable mineralization sites in the form of association rules, it would contribute to a deeper understanding of the underlying mechanisms governing the formation of structure-controlled orogenic gold deposits in the Jiaojia goldfield.

Change detection has been increasingly studied in remote and close-range sensing in the last decades, driven by its importance in environment monitoring and database updating. Due to the development of sensing technologies, data acquisition has become more accessible and affordable and thus more data from various sensing platforms have become available. Thanks to structure-from-motion photogrammetry and lidar technologies, 3D change detection from point cloud data is drawing considerable attention in recent years. Motivated by the lack of a comprehensive review of 3D change detection in the urban environment, this paper reviews the latest developments in urban object change detection using point cloud data. In particular, four types of objects, namely building, street scene, urban tree, and construction site, are analysed in-depth. The use of different data sources for each object-of-interest and the open-source data with change labels are summarised. Then the change detection methods are thoroughly reviewed at pixel, point, voxel, segment and object levels, whose pros and cons are analysed in detail. Moreover, the challenges and opportunities brought by point cloud data and new methods, such as Siamese network deep learning, are discussed for future considerations.

Abstract Background The COVID-19 pandemic has highlighted the importance of whole genome sequencing (WGS) of SARS-CoV-2 to inform public health policy. By enabling definition of lineages it facilitates tracking of the global spread of the virus. The evolution of new variants can be monitored and knowledge of specific mutations provides insights into the mechanisms through which the virus increases transmissibility or evades immunity. To date almost 1 million SARS-CoV-2 genomes have been sequenced by members of the COVID-19 Genomics UK (COG-UK) Consortium. To achieve similar feats in a more cost-effective and sustainable manner in future, improved high throughput virus sequencing protocols are required. We have therefore developed a miniaturized library preparation protocol with drastically reduced consumable use and costs. Results We present the ‘Mini-XT’ miniaturized tagmentation-based library preparation protocol available on protocols.io ( https://doi.org/10.17504/protocols.io.bvntn5en ). SARS-CoV-2 RNA was amplified using the ARTIC nCov-2019 multiplex RT-PCR protocol and purified using a conventional liquid handling system. Acoustic liquid transfer (Echo 525) was employed to reduce reaction volumes and the number of tips required for a Nextera XT library preparation. Sequencing was performed on an Illumina MiSeq. The final version of Mini-XT has been used to sequence 4384 SARS-CoV-2 samples from N. Ireland with a COG-UK QC pass rate of 97.4%. Sequencing quality was comparable and lineage calling consistent for replicate samples processed with full volume Nextera DNA Flex (333 samples) or using nanopore technology (20 samples). SNP calling between Mini-XT and these technologies was consistent and sequences from replicate samples paired together in maximum likelihood phylogenetic trees. Conclusions The Mini-XT protocol maintains sequence quality while reducing library preparation reagent volumes eightfold and halving overall tip usage from sample to sequence to provide concomitant cost savings relative to standard protocols. This will enable more efficient high-throughput sequencing of SARS-CoV-2 isolates and future pathogen WGS.

Abstract Knowledge of the changes in the immune microenvironment during pulmonary bacterial acute and chronic infections is limited. The dissection of immune system may provide a basis for effective therapeutic strategies against bacterial infection. Here, we describe a single immune cell atlas of mouse lungs after acute and chronic Pseudomonas aeruginosa infection using single‐cell transcriptomics, multiplex immunohistochemistry, and flow cytometry. Our single‐cell transcriptomic analysis revealed large‐scale comprehensive changes in immune cell composition and high variation in cell–cell interactions after acute and chronic P. aeruginosa infection. Bacterial infection reprograms the genetic architecture of immune cell populations. We identified specific immune cell types, including Cxcl2+ B cells and interstitial macrophages, in response to acute and chronic infection, such as their proportions, distribution, and functional status. Importantly, the patterns of immune cell response are drastically different between acute and chronic infection models. The distinct molecular signatures highlight the importance of the highly dynamic cell–cell interaction process in different pathological conditions, which has not been completely revealed previously. These findings provide a comprehensive and unbiased immune cellular landscape for respiratory pathogenesis in mice, enabling further understanding of immunologic mechanisms in infection and inflammatory diseases.

Safety helmets are essential in various indoor and outdoor workplaces, such as metallurgical high-temperature operations and high-rise building construction, to avoid injuries and ensure safety in production. However, manual supervision is costly and prone to lack of enforcement and interference from other human factors. Moreover, small target object detection frequently lacks precision. Improving safety helmets based on the helmet detection algorithm can address these issues and is a promising approach. In this study, we proposed a modified version of the YOLOv5s network, a lightweight deep learning-based object identification network model. The proposed model extends the YOLOv5s network model and enhances its performance by recalculating the prediction frames, utilizing the IoU metric for clustering, and modifying the anchor frames with the K-means++ method. The global attention mechanism (GAM) and the convolutional block attention module (CBAM) were added to the YOLOv5s network to improve its backbone and neck networks. By minimizing information feature loss and enhancing the representation of global interactions, these attention processes enhance deep learning neural networks’ capacity for feature extraction. Furthermore, the CBAM is integrated into the CSP module to improve target feature extraction while minimizing computation for model operation. In order to significantly increase the efficiency and precision of the prediction box regression, the proposed model additionally makes use of the most recent SIoU (SCYLLA-IoU LOSS) as the bounding box loss function. Based on the improved YOLOv5s model, knowledge distillation technology is leveraged to realize the light weight of the network model, thereby reducing the computational workload of the model and improving the detection speed to meet the needs of real-time monitoring. The experimental results demonstrate that the proposed model outperforms the original YOLOv5s network model in terms of accuracy (Precision), recall rate (Recall), and mean average precision (mAP). The proposed model may more effectively identify helmet use in low-light situations and at a variety of distances.

ObjectiveMoyamoya disease (MMD) is a unique cerebrovascular occlusive disease characterized by progressive steno-occlusion within the terminal segment of the internal carotid artery. However, good collaterals from an external carotid artery are essential to compensate for the ischemia in moyamoya disease. This study aimed to investigate the transforming growth factor-beta 1 (TGFβ1) in plasma as a potential biomarker for predicting collateral formation in ischemic MMD.MethodsThe transcriptome profile downloaded from Gene Expression Omnibus (GEO) was used to analyze the differential expression of genes between the ischemic MMD and the control groups. We prospectively recruited 23 consecutive patients with ischemic MMD that was diagnosed via digital subtraction angiography (DSA). Nine patients with intracranial aneurysms and four healthy people served as controls. The collaterals from the external carotid artery were examined using DSA. We evaluated whether the collateral formation was associated with TGFβ1 in patients with ischemic MMD. Western blot, RT-qPCR, ELISA, and tube formation assay were used to explore the relationship between TGFβ1 and angiogenesis, as well as the potential mechanisms.ResultsThe mRNA levels of TGFβ1 were upregulated in the patients with ischemic MMD. The plasma TGFβ1 levels were higher in the patients with ischemic MMD than in the aneurysm and healthy patients (p < 0.05). The collateral formation group has higher levels of serum TGFβ1 than the non-collateral formation group (p < 0.05). The levels of vascular endothelial growth factor (VEGF) are positively correlated with TGFβ1 levels in the plasma (R2 = 0.6115; p < 0.0001). TGFβ1 regulates VEGF expression via the activation of the TGFβ pathway within HUVEC cells, as well as TGFβ1 stimulating HUVEC cells to secrete VEGF into the cell culture media. An in vitro assay revealed that TGFβ1 promotes angiogenesis within the endothelial cells.ConclusionOur findings suggest that TGFβ1 plays a vital role in promoting collateral formation by upregulating VEGF expression in ischemic MMD.

NF-κB signalling is critical to TLR mediated cytokine release in various immune responses. Here the authors show how N4BP1 inhibits NEMO signalling and subsequent NF-κB activation and how this pathway is negatively regulated by caspase-8 cleavage of N4BP1.

Specific emitter identification (SEI) uses the unintentional modulation information carried by the emitter waveform, i.e., radio frequency fingerprints, to realize the matching identification of the received signal and its corresponding emitter. We propose an emitter identification scheme based on deep learning (DL). The received signal is subjected to time-varying filtered empirical mode decomposition (tvf-EMD). The obtained intrinsic mode functions (IMFs) are subjected to Hilbert transformation to obtain a 3D-Hilbert spectrum, using amplitude frequency aggregation characteristics obtained by projection to express the nonstationary information of the signal and calculate its bispectral diagonal slice as the second feature. A squeeze-and-excitation block (SEB) is introduced to a convolutional neural network (CNN) to focus on the effective area in the feature map, and support vector machine (SVM) is used to fuse the decision information of the two types of features. We collect four types of steady-state signals on a software-defined radio (SDR) sensor platform based on GNU Radio and universal software radio peripherals (USRP), and study the algorithm performance. The results show that our scheme has strong generalization, high recognition accuracy, and broad application prospects compared with other SEI methods.

Lightning and precipitation data were used to analyze the lightning and rainfall characteristics during "6·27" super rainstorm of Hubei Province in 2020. The results showed that lightning in this rainfall event is dominated by negative lightning, although proportion of positive lightning was higher than statistical value. Positive lightning had active phases at the beginning and end of heavy rainfall, while negative lightning became active when heavy rainfall emerged. Lightning concentrated regions are located on the southern area of 850 hPa warm shear which was the exit region of low-level jet. High frequency regions were areas between the end of 700 hPa and 850 hPa warm shear line or the left of low and ultra-low jet flow. The area of lightning and rainfall had obvious corresponding relation. That is, high frequency regions and areas with rainfall higher than 50 mm were almost coincided. Lightning concentrated regions were almost coincident with areas with rainfall higher than 40 mm·h-1. Lightning concentrated regions located at the center and leading edge of intense precipitation, negative lightning corresponded with relatively strong rainfall, and proportion of positive lightning increased on the edge of storms. Lightning frequency had a consistent trend with rainfall, and the peak of lightning might be either ahead or behind rainfall maxima in different storms.

Abstract Ultralong room‐temperature phosphorescence (RTP) is highly useful for information encryption, organic electronics, bioelectronics, etc. However, the preparation of related metal‐free materials with multiple colors across the full spectrum remains a major challenge. Herein, a facile method is developed to fabricate boron‐doped carbon dot (B‐CD) composites with full‐color long lifetime RTP continuously tailorable in the range of 466–638 nm simply by pyrolysis of the citric acid and boric acid precursors with various mass ratios at different temperatures. This leads to the formation of luminescent B‐CD centers in a rigid polycrystalline B2O3 matrix, which effectively stabilizes the triplet excited states of B‐CDs. Thus, the composites become phosphorescent over a relatively long period (5–12 s) after the removal of the irradiation source. Meanwhile, the increased particle size and oxidation degree of B‐CDs obtained at larger citric acid feeding or higher pyrolysis temperature continuously shift the phosphorescence from blue to red. Due to the formation of multiple luminescence centers, the RTP can also be finely modulated by the excitation wavelength. The resulting B‐CD composites with highly tunable long lifetime RTP further allow a variety of distinctive applications in multidimensional encryption handily utilizing space, time, and color variations.

Much of the existing research on banking systemic risk focuses on static single-risk exposures, and there is a lack of research on multiple-risk exposures. The reality is that the banking system is facing an increasingly complex environment, and dynamic measures of multiple-risk integration are essential. To reveal the risk accumulation process under the multi-risk exposures of the banking system, this article constructs a dynamic banking system as the research object and combines geometric Brownian motion, the BSM model, and the maximum likelihood estimate method. This article also aims to incorporate three types of exposures (interbank lending market risk exposures, entity industry credit risk exposures, and market risk exposures) within the same framework for the first time and builds a model of the dynamic evolution of banking systemic risk under multiple exposures. This study included the collection of a large amount of real data on banks, entity industries, and market risk factors, and used the ΔCoVaR model to evaluate the systemic risk of the China banking system from the point of view of the accumulation of risk from different exposures, revealing the dynamic process of risk accumulation under the integration of multiple risks within the banking system, as well as the contribution of different exposures to banking systemic risk. The results showed that the banking systemic risk of China first increased and then decreased with time, and the rate of risk accumulation is gradually slowing down. In terms of the impact of different kinds of exposures on system losses, the credit risk exposure of the entity industry had the greatest impact on the banking systemic risk among the three kinds of exposures. In terms of the contribution of the interbank lending market risk to the systemic risk, the Bank of Communications, China Everbright Bank, and Bank of Beijing contributed the most. In terms of the contribution of the bank–entity industry credit risk to the systemic risk, the financial industry, accommodation and catering industry, and manufacturing industry contributed the most. Considering the contribution of market risk to the systemic risk, the Shanghai Composite Index, the Hang Seng Composite Index, and the Dow Jones Index contributed the most. The research in this paper enriches the existing banking systemic risk research perspective and provides a reference for the regulatory decisions of central banks.

Summary: We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.

Identifying when agricultural expansion has occurred and how it altered the landscape is critical for understanding human social survival strategies as well as current ecological diversity. In the present study, phytolith records of three profiles from the Baodun site area were dated to the period from 7,500 to 2,500 aBP by optically stimulated luminescence and 14C dating, providing the first evidence that the Asian cultivated rice (Oryza sativa) progenitor was distributed in the Chengdu Plain as early as 7,500 aBP. The percentage of rice bulliform with ≥9 scales and the concentration of rice phytoliths sharply increased by approximately 4,200 aBP, suggesting that rice cultivation occupied a dominant position in survival strategy no later than approximately 4,200 aBP, which might be driven by climate deterioration in eastern China. The results further showed that the proportion of Bambusoideae phytoliths increased synchronously with the increase in the proportion of rice phytoliths, suggesting that the vegetation structure near the site was changed intentionally as a consequence of increasing rice agricultural activity since 4,200 aBP. The present study contributes to a deeper understanding of the distribution of wild rice and rice farming throughout the Baodun culture in the Chengdu Plain, and it also provides a glimpse of how humans intentionally changed the vegetation landscape on a local scale.

Silica-based nanoframeworks have been extensively studied for diagnosing and treating hepatocellular carcinoma (HCC). Several reviews have summarized the advantages and disadvantages of these nanoframeworks and their use as drug-delivery carriers. Encouragingly, these nanoframeworks, especially those with metal elements or small molecular drugs doping into the skeleton structure or modifying onto the surface of nanoparticles, could be multifunctional components participating in HCC diagnosis and treatment rather than functioning only as drug-delivery carriers. Therefore, in this work, we described the research progress of silica-based nanoframeworks involved in HCC diagnosis (plasma biomarker detection, magnetic resonance imaging, positron emission tomography, photoacoustic imaging, fluorescent imaging, ultrasonography, etc.) and treatment (chemotherapy, ferroptotic therapy, radiotherapy, phototherapy, sonodynamic therapy, immunotherapy, etc.) to clarify their roles in HCC theranostics. Further, the future expectations and challenges associated with silica-based nanoframeworks were highlighted. We believe that this review will provide a comprehensive understanding for researchers to design novel, functional silica-based nanoframeworks that can effectively overcome HCC.

Ozone (O3) is an important secondary substance that plays a significant role in atmospheric chemistry and climate change. Although O3 is essential in the stratosphere, it is harmful to human health in the troposphere, where this study was conducted. In recent years, O3 pollution in the Beijing-Tianjin-Hebei (BTH), Yangtze River Delta (YRD), and Pearl River Delta (PRD) regions has deteriorated, which has become an important environmental problem. The generation of O3 is closely related to meteorological factors. In this study, the weather classification method was adopted to study the effect of meteorological conditions on O3 concentration. In the BTH region, Tianjin was selected as the representative city for the research. The real-time pollutants data, meteorological re-analysis data, and meteorological data in 2019 were combined for the analysis. The subjective weather classification method was adopted to investigate the effects of different weather types on O3 concentration. The backward trajectory tracking model was used to explore the characteristics and changes of O3 pollution under two extreme weather types. The results indicate there is a good correlation between O3 concentration and ambient temperature. Under the control of low pressure on the ground and the influence of southwest airflow in the upper air for Tianjin, heavy O3 pollution occurred frequently. The addition of external transport and local generation will cause high O3 values when the weather system is weak. The O3 concentration is closely related to ambient temperature. Continuous high-temperature weather is conducive to the photochemical reaction. The multi-day O3 pollution process would occur when the weather system is robust. The first and second types of extreme weather are more likely to cause persistent O3 pollution processes. Under the premise of stable emission sources, the change in weather patterns was the main reason affecting the O3 concentration. This study aims to improve O3 pollution control and air quality prediction in the BTH region and large cities in China.

Ship emissions are one of the main sources of air pollution in port cities. The prosperous maritime trade has brought great harm to the air quality of port cities while promoting the development of the world economy. During the berthing process, ship auxiliary machines emit a large amount of air pollutants, which have a great impact on air quality and public health. Alternative marine fuels are being studied and used frequently to reduce ship emissions. This research was carried out to investigate the gaseous and particles emission characteristics of a marine diesel engine during the application of experimental biodiesel fuels. To study the influence of mixed fuels on engine performance, measurements were made at different engine loads and speeds. Different diesel fuels were tested using various ratios between biodiesel and BD0 (ultra-low sulfur diesel) of 0%, 10%, 30%, 50%, 70%, 90%, and 100%. The results indicated the use of biodiesel has little influence on the combustion performance but has a certain impact on exhaust emissions. The octane number and laminar flame speed of biodiesel are higher than those of BD0, so the combustion time of the test diesel engine is shortened under the mixed mode of biodiesel. In addition, a high ratio of biodiesel leads to a decrease of the instantaneous peak heat release rate, causing the crank angle to advance. As the biodiesel blending ratio increased, most of the gaseous pollutants decreased, especially for CO, but it led to an increase of particle numbers. The particle size distribution exhibits a unimodal distribution under various conditions, with the peak value appearing at 30–75 nm. The use of biodiesel has no effect on this phenomenon. The peak positions strongly depend on fuel types and engine conditions. The particulate matter (PM) emitted from the test engine included large amounts of organic carbon (OC), which accounted for between 30% and 40% of PM. Whereas the elemental carbon (EC) accounted for between 10% and 20%, the water-soluble ions components accounted for 6–15%. Elemental components, which accounted for 3–8% of PM emissions, mainly consisted of Si, Fe, Sn, Ba, Al, Zn, V, and Ni. Generally, biodiesel could be a reliable alternative fuel to reduce ship auxiliary engine emissions at berth and improve port air quality.

Background/Aims: Disseminated tumors, known as metastases, are responsible for ninety-percent of mortality due to cancer. Epithelial to mesenchymal transition, a phenomenon required for morphological conversion of non-motile discoid shaped epithelial cells to highly motile spindle-shaped mesenchymal cells, is thought to be a pre-requisite for metastatic progression. Metastasis-associated 1 (MTA1) protein is a prime inducer of EMT and metastatic progression in all solid tumors including hepatocellular carcinoma (HCC). However, the molecular mechanisms that regulate the expression and function of MTA1 in HCC have not been elucidated. Methods: In silico prediction algorithms were used to find microRNAs (miRNAs) that may target MTA1. We examined the relationship between the expression of MTA1 and miR-183 using quantitative real time PCR. We also determined the levels of the MTA1 protein using immunohistochemistry. Reporter assays, in the presence and absence of the miR-183 mimic, were used to confirm MTA1 as a bona fide target of miR183. The effect of miR-183 on HCC pathogenesis was determined using a combination of in vitro migration and invasion assay, together with in vivo xenograft experiments. The correlation between miR-183 and MTA1 expression was also studied in samples from HCC patients, and in The Cancer Genome Atlas dataset. Results: Analysis of the sequence database revealed that MTA1 is a putative target of miR-183. MTA1 protein and RNA expression showed opposite trends to miR-183 expression in breast, renal, prostate, and testicular tissue samples from cancer patients, and in the metastatic HCC cell line HepG2. An inverse correlation was also observed between MTA1 (high) and miR-183 (low) expression within samples from HHC patients and in the TCGA dataset. Reporter assays in HepG2 cells showed that miR-183 could inhibit translation of a reporter harboring the wild-type, but not the mutant miR-183 3’-untranslated region (UTR). In addition, miR-183 significantly inhibited in vitro migration and invasion in HepG2 cells, and in vivo hepatic metastasis. Conclusion: Our results reveal a novel post-transcriptional regulatory mechanism for MTA1 expression via miR-183, which is suppressed during HCC pathogenesis.

The aim of this research was to quantitatively and comprehensively explore the therapeutic effects and mechanism of action of traditional Chinese medicine (TCM) formulas, using Periplaneta americana as a monarch drug, against damp-heat ulcerative colitis (UC) in rats, by the application of multivariate statistical analysis. A high-sugar and high-fat diet was fed to Sprague Dawley (SD) male rats to develop the damp-heat physique. Trinitrobenzene sulfonic acid (TNBS) was then used on the damp-heat rats to induce UC. P. americana (P), Taraxacum mongolicum (T), and Poria cocos (F) have been in combination or individually adopted as ingredients in different TCM pharmaceutics to attenuate damp-heat physiques and/or to treat UC, because P. americana could promote blood circulation, nourish yin, and promote tissue regeneration, T. mongolicum has the effects on clearing heat and toxic materials, reduce swelling, and diuresis, while P. cocos possesses the function of clearing damp and promoting diuresis. Since these natural ingredients of TCM demonstrated overlapped effects against damp-heat UC, it calls the need to further illustrate the therapeutic effect and mechanism of action of P. americana as the monarch drug by comparing the effects of formulas of PT, PF, TF, and PTF. Each formula was administered by gastric lavage to four groups of randomly assigned laboratory animals for 14 consecutive days, while normal saline was given to the normal control and model control groups respectively. The damp-heat and UC indices, bio-marker levels in serum, and colonic mucosa were measured periodically, or the day after the last administration. The results of canonical correlation analysis and repeated-measures analysis of variance suggested that the therapeutic effects of formulas containing P. americana and T. mongolicum were better than those of the other formulas. The results of correspondence analysis suggested that the curative effects against damp-heat UC might be activated by reducing the expression of Interleukin-2 (IL-2) and increasing the level of transforming growth factor-beta (TGF-β). The organically combined use of multiple multivariate statistical methods allowed comprehensive evaluation of the therapeutic effects of TCM formulas against chronic diseases with complex pathogenic factors.

In multiattribute group decision-making (MAGDM), due to quantity, fuzziness, and complexity of evaluation linguistic information on commodities, traditional distance measures need to be extended to the integration of evaluation information under a multigranular probabilistic linguistic environment. A more reasonable method is proposed to deal with the missing value in the evaluation information. On the basis of the generalized distance measures and filling in the missing evaluation information, some novel distance measures between two multigranular probabilistic linguistic term sets (PLTSs) are presented in this paper. Based on these distance measures, three extended decision-making (DM) algorithms based on TOPSIS, the extended TOPSIS, and VIKOR are proposed, which are MGPL-TOPSIS, MGPL-ETOPSIS, and MGPL-VIKOR, respectively. The case analyses on purchasing a car are provided to illustrate the application of the extended multiattribute group decision-making (MAGDM) algorithms. Then, sensitivity analyses based on PT are proposed as well. In particular, the extended TOPSIS method is presented. These results demonstrate the novelty, feasibility, and rationality of the distance measures between two multigranular PLTSs proposed in this paper.

Autism spectrum disorder (ASD) is a constellation of neurodevelopmental disorders with high phenotypic and genetic heterogeneity, complicating the discovery of causative genes. Through a forward genetics approach selecting for defective vocalization in mice, we identified Kdm5a as a candidate ASD gene. To validate our discovery, we generated a Kdm5a knockout mouse model (Kdm5a-/-) and confirmed that inactivating Kdm5a disrupts vocalization. In addition, Kdm5a-/- mice displayed repetitive behaviors, sociability deficits, cognitive dysfunction, and abnormal dendritic morphogenesis. Loss of KDM5A also resulted in dysregulation of the hippocampal transcriptome. To determine if KDM5A mutations cause ASD in humans, we screened whole exome sequencing and microarray data from a clinical cohort. We identified pathogenic KDM5A variants in nine patients with ASD and lack of speech. Our findings illustrate the power and efficacy of forward genetics in identifying ASD genes and highlight the importance of KDM5A in normal brain development and function.

The flow channel design of bipolar plates plays a significant role in the proton exchange membrane fuel cells operation, particularly in thermal and water management. The pursuit of low-pressure drop supply and flow field uniformity in PEM fuel cells has not stopped, resulting in numerous new bipolar plate flow channel designs. The biomimetic leaf vein shape-based flow channel and lung flow channel designs can significantly improve gas supply uniformity and reduce pressure drop. Therefore, we propose a snowflake-shaped bionic channel design by integrating the advantages of the leaf vein shape and lung shape channel. A 3D multi-physics fuel cell model is used to verify the feasibility and superiority of the bionic snowflake design in improving fuel cell performance, especially in reducing the pumping work. The local pressure distribution, oxygen distribution, water distribution, and current density distribution are used to reveal the enhancement mechanism of the new snowflake flow channel. The flow uniformity is further enhanced by using multi-objective (13 target parameters) and multi-parameter (18 independent variables) genetic algorithm optimization. The general goal of this work is to provide a new strategy for the thermal and water management of PEM fuel cells.

This study was designed to investigate the effects of early coelom continued circulatory hyperthermic perfusion chemotherapy combined with systemic chemotherapy on the survival and serum tumor markers. A total of 128 patients with advanced gastric carcinoma who have received surgical treatments were selected and were randomly divided into study group (receiving early circulatory intraperitoneal hyperthermic perfusion chemotherapy combined with systemic chemotherapy postoperatively) and control group (receiving chemotherapy alone postoperatively), with 64 cases in each. Comparison of serum tumor markers (CA724, CA242), vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), immune function indexes (CD 3 + , CD 4 + , CD 8 + ), and 5-year survival rate was assessed. Before treatment, there was no significant difference in the serum tumor markers (CA724 and CA242) as well as the serum VEGF, MMP-2, and MMP-9 levels among the two groups ( P > 0.05). However, the above parameters in the study group were significantly lower than control group 8 weeks after the treatment ( P 0.05). Eight weeks after the treatment, the CD 3 + , CD 4 + and CD 4 + /CD 8 + in the study group were significantly higher than those in the control group ( P

Ulcerative colitis (UC) is a chronic inflammatory disease of intestinal tract, and Periplaneta americana has been found to be effective in the treatment for UC. The purpose of the study was to investigate the therapeutic effect of Periplaneta americana extract Ento-A on UC in rats induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) and to explore its mechanism. The Sprague-Dawley (SD) rats were randomly divided into normal control group; TNBS-treated group; sulfasalazine (SASP) treated group; Ento-A low- (50 mg/kg), medium- (100 mg/kg), and high-dose (200 mg/kg) groups, respectively. The UC model of rats was induced via TNBS. Disease activity index (DAI) was used to evaluate the severity of UC in rats. The macroscopic and microscopic damages of colon were accessed by colon mucosa damage index (CMDI) and histopathological score (HS), respectively. The levels of interleukin-4 (IL-4), interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in serum and the contents of myeloperoxidase (MPO), transforming growth factor-β1 (TGF-β1), and epidermal growth factor (EGF) in colonic mucosa were measured by enzyme-linked immunosorbent assay (ELISA). Compared with the normal control group, the TNBS-treated group showed increase in DAI, CMDI, HS, IL-17, TNF-α, IFN-γ as well as MPO and decrease in the levels of IL-4, EGF, and TGF-β1. However, Ento-A-administrated groups reversed the changes in the DAI, CMDI, HS, and the cytokines caused by TNBS. The study indicates that Periplaneta americana extract Ento-A can effectively alleviate the inflammation in TNBS-induced UC of rats, and the mechanism of that may be related to restoring the balance of T helper 1 (Th1)/Th2/Th17/T regulatory (Treg) cytokines.

Blood–retinal barrier (BRB) dysfunction underlies macular oedema in many sight-threatening conditions, including diabetic macular oedema, neovascular age-related macular degeneration and uveoretinitis. Inflammation plays an important role in BRB dysfunction. This study aimed to understand the role of the inflammatory cytokine IL-17A in BRB dysfunction and the mechanism involved. Human retinal pigment epithelial (RPE) cell line ARPE19 and murine brain endothelial line bEnd.3 were cultured on transwell membranes to model the outer BRB and inner BRB, respectively. IL-17A treatment (3 days in bEnd.3 cells and 6 days in ARPE19 cells) disrupted the distribution of claudin-5 in bEnd.3 cells and ZO-1 in ARPE19 cells, reduced the transepithelial/transendothelial electrical resistance (TEER) and increased permeability to FITC-tracers in vitro. Intravitreal (20 ng/1 μL/eye) or intravenous (20 ng/g) injection of recombinant IL-17A induced retinal albumin leakage within 48 h in C57BL/6J mice. Mechanistically, IL-17A induced Janus kinase 1 (JAK1) phosphorylation in bEnd.3 but not ARPE19 cells. Blocking JAK1 with Tofacitinib prevented IL-17A-mediated claudin-5 dysmorphia in bEnd.3 cells and reduced albumin leakage in IL-17A-treated mice. Our results suggest that IL-17A can damage the BRB through the activating the JAK1 signaling pathway, and targeting this pathway may be a novel approach to treat inflammation-induced macular oedema.

Polyhaloaromatic compounds (XAr) are ubiquitous and recalcitrant in the environment. They are potentially carcinogenic to organisms and may induce serious risks to the ecosystem, raising increasing public concern. Therefore, it is important to detect and quantify these ubiquitous XAr in the environment, and to monitor their degradation kinetics during the treatment of these recalcitrant pollutants. We have previously found that unprecedented intrinsic chemiluminescence (CL) can be produced by a haloquinones/H2O2 system, a newly-found ●OH-generating system different from the classic Fenton system. Recently, we found that the degradation of priority pollutant pentachlorophenol by the classic Fe(II)-Fenton system could produce intrinsic CL, which was mainly dependent on the generation of chloroquinone intermediates. Analogous effects were observed for all nineteen chlorophenols, other halophenols and several classes of XAr, and a novel, rapid and sensitive CL-based analytical method was developed to detect these XAr and monitor their degradation kinetics. Interestingly, for those XAr with halohydroxyl quinoid structure, a Co(II)-mediated Fenton-like system could induce a stronger CL emission and higher degradation, probably due to site-specific generation of highly-effective ●OH. These findings may have broad chemical and environmental implications for future studies, which would be helpful for developing new analytical methods and technologies to investigate those ubiquitous XAr.

Aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) is a member of the basic helix-loop-helix/PER-ARNT-SIM (bHLH/PAS) transcription factor family. ARNT2 heterodimerizes with several members of the family, including single-minded homolog-1 (SIM1) and neuronal PAS domain protein 4 (NPAS4), primarily in neurons of the central nervous system. We screened 64,424 third-generation germline mutant mice derived from N-ethyl-N-nitrosourea (ENU)-mutagenized great-grandsires for weight abnormalities. Among 17 elevated body weight phenotypes identified and mapped, one strongly correlated with an induced missense mutation in Arnt2 using a semidominant model of inheritance. Causation was confirmed by CRISPR/Cas9 gene targeting to recapitulate the original ENU allele, specifying Arg74Cys (R74C). The CRISPR/Cas9-targeted (Arnt2R74C/R74C) mice demonstrated hyperphagia and increased adiposity as well as hepatic steatosis and abnormalities in glucose homeostasis. The mutant ARNT2 protein showed decreased transcriptional activity when coexpressed with SIM1. These findings establish a requirement for ARNT2-dependent genes in the maintenance of the homeostatic feeding response, necessary for prevention of obesity and obesity-related diseases.

Caffeic acid phenethyl ester (CAPE) and its structurally-related caffeic acid (CA), ferulic acid (FA) and ethyl ferulate (EF) are constituents of honeybee propolis that have important pharmacological activities. This study found that CAPE—but not CA, FA, and EF—could effectively prevent cellular DNA damage induced by overloaded iron through decreasing the labile iron pool (LIP) levels in HeLa cells. Interestingly, CAPE was found to be more effective than CA in protecting against plasmid DNA damage induced by Fe(II)–H2O2 or Fe(III)–citrate–ascorbate-H2O2 via the inhibition of hydroxyl radical (•OH) production. We further provided more direct and unequivocal experimental evidences for the formation of inactive CAPE/CA–iron complexes. CAPE was found to have a stronger iron-binding ability and a much higher lipophilicity than CA. Taken together, we propose that the esterification of the carboxylic moiety with phenethyl significantly enhanced the iron-binding ability and lipophilicity of CAPE, which is also responsible for its potent protection against iron-mediated cellular DNA damage. A study on the iron coordination mechanism of such natural polyphenol antioxidants will help to design more effective antioxidants for the treatment and prevention of diseases caused by metal-induced oxidative stress, as well as help to understand the structure–activity relationships of these compounds.

The southwest Indian Ocean is an important area for deep-sea investigation and exploration. In this paper, the spatial distribution and temporal variation characteristics of wave elements in the sea area were analyzed by using the high resolution reanalysis data (ERA) from the European Center, the optimal path set of tropical cyclones provided by the Joint Warning Center (JTWC) and the global ocean circulation model (OFES). The results show that the monthly mean effective wave height in the southwest Indian Ocean is relatively large, ranging from 3.5m to 5.5m. the wave season is relatively stable, with the highest mean wave height in winter and the lowest mean wave height in summer; The frequency of tropical cyclones is higher in summer and autumn and lower in winter; The most suitable operation time of manned submersible in the southwest Indian Ocean is from November to march of the next year, and other time needs to select good sea conditions for operation.