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Abstract The mantle plumes modify geophysical and geochemical features along and across mid‐ocean ridges. Despite abundant studies of plume‐ridge interaction, few geodynamic studies focus on the Arctic Ocean. The Jan Mayen Hotspot is located at the southern end of the Mohns Ridge and offset by the Jan Mayen Transform Fault, which creates an ideal area to study plume‐ridge‐transform fault interaction at the ultra‐slow spreading ridge. Through analyzing geophysical observations, we revealed that the M factor and crustal thickness decrease and the axial relief increases northeastward along the Mohns Ridge within a distance of ∼370 km to the Jan Mayen Hotspot. Combined with modeling results, the properties of the Jan Mayen plume were estimated, which has a diameter of 75 km, a temperature anomaly of 100°C, and a buoyancy flux of 0.22 Mg/s. Additionally, our model results indicate that the along‐ridge dispersion of plume is slightly enhanced by the transform fault.

ABSTRACTIntestinal epithelial cell (IEC) regulation of barrier function and mucosal homeostasis enables the establishment of a harmonious gut microenvironment. However, host-derived regulatory networks that modulate intestinal antimicrobial defenses have not been fully defined. Herein we generated mice with IEC-specific deletion of Gpr65 (Gpr65ΔIEC) and investigated the role of epithelial GPR65 using DSS- and C. rodentium-induced murine colitis models. RNA sequencing analysis was conducted on colonic IECs from Gpr65fl/fl and Gpr65ΔIEC mice, and colonoids and colonic epithelial cell lines were used to evaluate the pH-sensing effect of GPR65. The expression of GPR65 was determined in IECs from patients with inflammatory bowel disease (IBD) and DSS colitis mice by qRT-PCR, Western blot, and immunohistochemistry, respectively. We observed that the absence of GPR65 in IECs abrogated homeostatic antimicrobial programs, including the production of antimicrobial peptides (AMPs) and defense response-associated proteins. Gpr65ΔIEC mice displayed dysbiosis of the gut microbiota and were prone to DSS- and C. rodentium-induced colitis, as characterized by significantly disrupted epithelial antimicrobial responses, pathogen invasion, and increased inflammatory infiltrates in the inflamed colon. RNA sequencing analysis revealed that deletion of GPR65 in IECs provoked dramatic transcriptome changes with respect to the downregulation of immune and defense responses to bacteria. Forced AMP induction assays conducted in vivo or in ex vivo colonoids revealed that IEC-intrinsic GPR65 signaling drove antimicrobial defense. Mechanistically, GPR65 signaling promoted STAT3 phosphorylation to optimize mucosal defense responses. Epithelial cell line and colonoid assays further confirmed that epithelial GPR65 sensing pH synergized with IL-22 to facilitate antimicrobial responses. Finally, the expression of GPR65 was markedly decreased in the inflamed epithelia of IBD patients and DSS colitis mice. Our findings define an important role of epithelial GPR65 in regulating intestinal homeostasis and mucosal inflammation and point toward a potential therapeutic approach by targeting GPR65 in the treatment of IBD.

Abstract Water is the most common volatile component inside the Earth. A substantial amount of water can be carried down to the interior of the Earth by subducting plates. However, how the subducted water evolves after the subducting slab breaks off remains poorly understood. Here we use the data from a passive seismic experiment using ocean bottom seismometers (OBSs) together with the land stations to determine the high-resolution, three-dimensional seismic structure of the Southwest Sub-basin (SWSB) of the South China Sea (SCS). At depths below 40 km, the mantle shear velocity (Vsv) beneath the northern side of the SWSB is similar to that of the conventional oceanic pyrolite mantle, but roughly 3% shear-velocity reduction is found beneath the southern side of the SWSB. Results of thermal dynamic modeling reveal that the observed shear-velocity reduction could be explained by the presence of 150–300 ppm of water and 5–10% of lower continental crust. The inferred high-water content at the southern side of the SWSB is consistent with a model in which the Proto-SCS plate subducted southward prior to and during the formation of the SCS basin, releasing water into the upper mantle of the SWSB.

The effect of the modification treatment on the refinement of primary carbides and wear resistance of 35% Cr-4.0% C hypereutectic high chromium cast iron (HHCCI) was investigated using the first-principles calculations, XRD, SEM, TEM, hardness tests, and wear tests. The addition of N elements to HHCCI refined the size of the M7C3 primary carbide from 13.25 ± 0.72 μm to 11.67 ± 0.33 μm under the effect of adsorption refinement. When the compound modification elements (N + Ti + V + RE-Mg) were added, the combination of adsorption refinement and heterogeneous nucleation refinement significantly reduced the carbide size to 5.35 ± 0.15 μm. The refinement of the M7C3 primary carbide can be attributed to two components: 1) the refinement of the heterogeneous nucleation of TiC and VC. 2) the combination of N, Ti, and V with the M7C3 preferred growth surface (0001) resulting in the refinement by adsorption and reduce the size of the primary carbide. The hypereutectic high chromium cast iron after the compound modification exhibited excellent wear resistance. Under dry sliding wear condition, Compared with the unmodified sample, the wear resistance increased by 75%. Under corrosive wear conditions, the wear resistance is increased by 98.1%.

Personalized quality of service （QoS） prediction is crucial for developing high-quality cloud service system.However, the traditional collaborative filtering method, based on centralized training, presents challenges in protecting user privacy.In order to effectively protect user privacy while obtaining highly accurate prediction effect, a distributed user privacy adjustable personalized QoS prediction model for cloud services （DUPPA） was proposed.The model adopted a “server-multi-user” architecture, in which the server coordinated multiple users, handled multiple users’ requests for uploading model gradients and downloading global model, and maintained global model parameters.To further protect user privacy, a user privacy adjustment strategy was proposed to balance privacy and prediction accuracy by adjusting the initialization proportion of local model parameters and gradient upload proportion.In the local model initialization stage, the user calculated the difference matrix between the local model and the global model, and selected the global model parameters corresponding to the larger elements in the difference matrix to initialize the local model parameters.In the gradient upload stage, the user can select some important gradients to upload to the server to meet the privacy protection requirements of different application scenarios.To evaluate the privacy degree of DUPPA, a data reconstruction attack method was proposed for the distributed matrix factorization model gradient sharing scheme.The experimental results show that when DUPPA sets the gradient upload proportion to 0.1 and the local model parameter initialization proportion to 0.5, the predicted MAE and RMSE are reduced by 1.27% and 0.91%, respectively, compared with the traditional centralized matrix factorization model.Besides, when DUPPA sets the gradient upload proportion to 0.1, the privacy degree is 5 times higher than when the gradient upload proportion is 1.And when DUPPA sets the local model parameter initialization proportion to 0.5, the privacy degree is 3.44 times higher than when the local model parameter initialization proportion is 1.

Abstract Background Hypothalamic hamartoma (HH) is a congenital non-progressive lesion of hypothalamus during fetal development. Mass-like lesions in different anatomical locations often develop a variously disabling course presenting with cognitive decline, psychiatric symptoms, as well as multiple seizure types. As a rare disease, HH is relatively common in infants and children, but it is extremely rare in adults. Case presentation We reported a case of adult-onset hypothalamic hamartoma, and summarized and analyzed relevant reports and studies of HH worldwide. The patient had clinical manifestations characterized by multiple seizure forms. After stereotactic radiofrequency thermocoagulation and drug treatment, the condition was effectively controlled. The patient was followed up till October 2022, with no recurrence of seizures. Conclusions Epilepsy caused by HH can resemble that of temporal lobe seizures, as HH forms a complex epileptogenic network with other regions of the brain through anatomical and functional connections. Early treatment of HH can provide better control of the symptoms of epilepsy, and patients with longer disease courses may have more complications.

Abstract We used deep-learning-based models to automatically obtain elastic moduli from resonant ultrasound spectroscopy (RUS) spectra, which conventionally require user intervention of published analysis codes. By strategically converting theoretical RUS spectra into their modulated fingerprints and using them as a dataset to train neural network models, we obtained models that successfully predicted both elastic moduli from theoretical test spectra of an isotropic material and from a measured steel RUS spectrum with up to 9.6% missing resonances. We further trained modulated fingerprint-based models to resolve RUS spectra from yttrium–aluminum-garnet (YAG) ceramic samples with three elastic moduli. The resulting models were capable of retrieving all three elastic moduli from spectra with a maximum of 26% missing frequencies. In summary, our modulated fingerprint method is an efficient tool to transform raw spectroscopy data and train neural network models with high accuracy and resistance to spectra distortion.

On May 21, a Ms6.4 earthquake occurred in Yangbi, Yunnan Province. Less than 5 ​h later, on May 21, follows a Ms7.4 earthquake in Madoi, Qinghai Province. In this study, multiple parameters are studied from CSES-01 satellite and GNSS. The parameters include the electron density from LAP, energetic particle flux from HEPP, electric field spectrum from EFD, induced magnetic field spectrum from SCM, and global TEC from ground-based GNSS receivers. In the time scale, all parameters changed on May 15, 17 and 18. The relative amplitude of Ne is more than 200%. In space scale, the clear enhancement focus on the southeast of the epicenter of Madoi, Qinghai, and the shape of the focus region is like a clockwise-30°-rotated rectangle, which is about 45° in length and 20° in width. Moreover, there appeared enhancement in the conjugated region. According to the day-to-day analysis of the low-frequency (75–90 Hz) spectrum of EFD and SCM payloads, the relationship of the increment on May 18 could be confirmed with the successive two earthquakes. The energetic particle fluxes enhanced on May 20. All those changes are located in the east of the following epicenter and appeared just several days before, which could be well explained by the Lithosphere-Atmosphere-Ionosphere theory.

In this study, four strains of lactic acid-producing bacteria were isolated from naturally fermented quinoa sour pulp by using plate separation technology with starch flocculation rate and lactic acid production as indicators. According to the morphological characteristics, physiological and biochemical experiments, and 16S rDNA sequence analysis, strain QSL4, QSL8, QSL9 and QSL12 were identified as Enterococcus faecium, Enterococcwus durans, Enterococcus mundtii and Enterococcus lactis, respectively. The isolated strains were applied to the extraction of quinoa protein, and its extraction characteristics in quinoa protein were analyzed by single factor experiments. The results showed that the extraction rate of quinoa protein by strain QSL12 was the highest, reaching 60.23% and 62.39% at the inoculum level of 7% and the fermentation temperature was 26 ℃, which were higher than the extraction rate results of 52.13% by alkali dissolution and acid precipitation method. This study would provide a foundation for quinoa protein extraction by acidic steeping liquor (ASL).

Agricultural activities are the second largest source of greenhouse gas emissions, and carbon emissions from agricultural land use (CEALU) have become a hot issue across the world. Although there are some studies on the impact of high-standard farmland construction policies on carbon emissions, they focus on quantitative analysis and do not give sufficient consideration to the relationship between HSFC and CEALU. Therefore, in this study, by relying on provincial panel data of China for the period 2005–2017, the effect of the high-standard basic farmland construction policy on carbon emissions from agricultural land use per unit area and its regional differences were quantitatively analyzed using the difference-in-difference (DID) model. The results showed that: (1) China’s CEALU per unit area presented a fluctuating upward change, but the growth rate slowed down during the period 2005–2017, from 392.58 kg/ha to 457.72 kg/ha, with an average annual growth rate of 1.31%; (2) the high-standard farmland construction (HSFC) policy led a significant carbon emission reduction effect in agricultural land use and reduced the CEALU per unit area by 10.80% on average. With the promotion of this policy, its carbon emission reduction effect in agricultural land use presented an overall increasing change; (3) the carbon emission reduction effect of the high-standard farmland construction policy in agricultural land use was significant in central China, but non-significant in eastern China and western China.

In recent years, advancement in biomedical sensors has led to increasingly accurate and accessible biological vital sign collection in nontraditional and noncontrolled application domains. Despite much progress, the implementation within the veterinary medicine field is still limited, which, in part, is due to a lack of rapid, robust, and easy-to-use sensors. To tackle this challenge this work presents a compact and wearable photoplethysmography (PPG) sensor for monitoring equine heart rates (HRs) from the ventral midline near the base of the tail. The PPG waveforms were robustly collected from a group of 50 equine subjects with various age, sex, and breed and then used for HR calculation. The system achieved an accuracy of 94% for HR calculation from the subjects at rest compared to the ground truth HRs acquired from the same subjects by a stethoscope. Statistical analysis on the collected data was conducted to further investigate the robustness of the HR calculations in different age, sex, and breed demographics. This work demonstrates that the PPG-based sensor for HR monitoring shows great potential of being a complementary tool in veterinary medicine for promoting furtherance of the animal health.

Graves' orbitopathy (GO) is an autoimmune disease that involves complex immune systems. The mainstays of clinical management for this disease are surgery, targeted drugs therapy, and no-targeted drugs drug therapy. targeted drugs can improve therapeutic efficacy and enhance the quality of life for GO patients. However, as a second-line treatment for GO, targeted drugs such as tocilizumab and rituximab have very limited therapeutic effects and may be accompanied by side effects. The introduction of Teprotumumab, which targets IGF-IR, has made significant progress in the clinical management of GO. The pathophysiology of GO still remains uncertain as it involves a variety of immune cells and fibroblast interactions as well as immune responses to relevant disease targets of action. Therfore, learning more about immune response feedback pathways and potential targets of action will assist in the treatment of GO. In this discussion, we explore the pathogenesis of GO and relevant work, and highlight four potential targets for GO: Interleukin-23 receptor (IL-23 R), Leptin receptor (LepR), Orbital fibroblast activating factors, and Plasminogen activator inhibitor-1 (PAI-1). A deeper understanding of the pathogenesis of GO and the role of potential target signaling pathways is crucial for effective treatment of this disease.

Abstract Individual tree structure mapping in cities is important for urban environmental studies. Despite mapping products for tree canopy cover and biomass are reported at multiple spatial scales using various approaches, spatially explicit mapping of individual trees and their three-dimensional structure is sparse. Here we produced an individual tree dataset including tree locations, height, crown area, crown volume, and biomass over the entire New York City, USA for 6,005,690 trees. Individual trees were detected and mapped from remotely sensed datasets along with their height and crown size information. Tree biomass in 296 field plots was measured and modelled using i-Tree Eco. Wall-to-wall tree biomass was mapped using relationships between field measurements and remotely sensed datasets and downscaled to individual trees. Validation using field-plot measurements indicated that our mapping products overestimated tree number, mean tree height and maximum tree height by 11.1%, 8.6%, and 5.3%, respectively. These overestimations were mainly due to the spatial and temporal mis-match between field measurements and remote sensing observations and uncertainties in tree segmentation algorithms. This dataset enables the evaluation of urban forest ecosystem services including regulating urban heat and promoting urban health, which can provide valuable insights for urban forest management and policy making.

Based on the thread score (TS), an improved verification index, the double-sided thread score (DTS), is proposed for precipitation forecast and service. TS only focuses on the forecasting skills of occurrence of events, but DTS takes into account the forecasting skills for both occurrence and non-occurrence of the events. The theoretical analysis and real cases show that DTS can help to improve the subjective or objective forecasts with BIAS closer to 1. The verification of annual precipitation forecast from 2007 to 2018 and daily precipitation forecast in 2019 shows that the DTS score decreases with the increase of the grade, and the scores of each grade are mostly higher than 0.5, so the score results are easier for the public to understand. In addition, the growth trend and fluctuation of prediction skills reflected by DTS are consistent with those by TS, which is convenient for comparison with historical scores.

Abstract With the widespread acceptance of the cloud-native concept and the emergence of a large number of dedicated cloud-native applications, the service stacks of cloud-native applications have received extensive attention in the industry. To analyze the extensibility problems of service stacks, a cloud-native light-cone model is proposed, which focuses on the dimensions of application, infrastructure, tenant and workflow, and provides a perspective view that reflects the concerns of stakeholders. Based on this model, various challenges in designing extensible cloud-native service stacks are identified by classification. To solve these challenges, a holistic architecture and a set of key technologies are designed, involving unified runtime abstraction, cluster bootstrapped creation, application-specific controllers, etc. Furthermore, the OMStack (Oriental Mind Stack) is implemented, which integrates these technologies and provides a group of PaaS and SaaS services for container cluster (OMCC), artificial intelligence (OMAI), big data (OMBD) and so on. Experimental analysis and production applications demonstrate the practicality, efficiency and reliability of the proposed architecture, stack and services.

Abstract Although human mobility is considered critical for the spread of the new coronavirus disease (COVID-19) both locally and globally, the extent to which such an association is impacted by social vulnerability remains unclear. Here, using multisource epidemiological and socioeconomic data of US counties, we develop a COVID-19 pandemic vulnerability index (CPVI) to quantify their levels of social vulnerability and examine how social vulnerability moderated the influence of mobility on disease transmissibility (represented by the effective reproduction number, R t) during the US summer epidemic wave of 2020. We find that counties in the top CPVI quintile suffered almost double in regard to COVID-19 transmission (45.02% days with an R t higher than 1) from mobility, particularly intracounty mobility, compared to counties in the lowest quintile (21.90%). In contrast, counties in the bottom CPVI quintile were only slightly affected by the level of mobility. As such, a 25% intracounty mobility change was associated with a 15.28% R t change for counties in the top CPVI quintile, which is eight times the 1.81% R t change for those in the lowest quintile. These findings suggest the need to account for the vulnerability of communities when making social distancing measures against mobility in the future.

Based on the ensemble precipitation prediction data of the European Centre for medium range weather forecast from 2018 to 2021, ensemble statistics area rainfall prediction products such as mode,mean,optimal percentile,percentile and probability have been developed. Threat score,bias score,relative operating characteristic (ROC) curve method,comprehensive performance diagram and brier skill score are used for verification to ensemble statistics area rainfall prediction products above heavy rain in the Yangtze River basin. Result shows that ensemble statistics area rainfall prediction products were superior to area rainfall forecasting calculated from deterministic precipitation prediction,and the score of plain area basin is higher than that of mountain basin for the area rainfall above heavy rain. There are differences in the types and ranking of the optimal areal rainfall quantitative prediction products in different sub basins of Yangtze River. The overall performance is that the median,mean and optimal percentile was the best,second and third in score among ensemble statistics area rainfall prediction products. The top three ideal ensemble statistics area rainfall prediction product were recommended according to the comprehensive verification result in each sub-basin of Yangtze River. The optimal probability forecast value corresponding to the best threat score of the probability forecast product gradually decreases with the increase of the area rainfall magnitude,and the optimal probability of area rainfall prediction above 15mm (40 mm) magnitude is 50%(30%). Taking the optimal TS score as the benchmark,the reference interval of areal rainfall probability forecast is obtained by floating down 10%. When the ensemble statistics areal rainfall probability forecast is located in the reference interval,the forecast reference value is higher. Taking the No. 5 flood process of the Yangtze River in 2020 as an example,the application analysis of the ensemble statistics area rainfall prediction product combining probability prediction and quantitative prediction recommendation products is carried out,which further shows that the error of the ensemble statistics area rainfall prediction product is significantly less than the deterministic forecast.

Monocyte chemotactic protein-1-induced protein-1 (MCPIP-1) is highly expressed in activated immune cells and negatively regulates immune responses, while the mechanisms underlying the immunoregulation of neutrophils in acute bacterial infection and liver injury remain elusive. Here, we examined the role of MCPIP-1 in regulating neutrophil functions during acute bacterial peritonitis and liver injury. Mice with myeloid cell-specific overexpression (McpipMye-tg) or knockout (McpipΔMye) of MCPIP-1 were generated. We found that reactive oxygen species and myeloperoxidase production, formation of neutrophil extracellular traps, and migratory capacity were deficient in McpipMye-tg neutrophils but enhanced in McpipΔMye neutrophils. The recruitment of neutrophils and pathogen clearance were markedly suppressed in McpipMye-tg mice following intraperitoneal infection with Salmonella typhimurium while intensified in McpipΔMye mice. Severe acute S. typhimurium-infected peritonitis and liver injury occurred in McpipMye-tg mice but were alleviated in McpipΔMye mice. RNA sequencing, RNA-binding protein immunoprecipitation and qPCR analysis revealed that MCPIP-1 downregulated the protective functions of neutrophils via degrading the mRNA of cold inducible RNA-binding protein. Consistently, MCPIP-1 was highly expressed in neutrophils of patients with acute infectious diseases, especially in those with liver injury. Collectively, we uncover that MCPIP-1 negatively regulates the antibacterial capacities of neutrophils, leading to exacerbating severe acute bacterial peritonitis and liver injury. It may serve as a candidate target for maintaining neutrophil homeostasis to control acute infectious diseases.

Abstract Background Previous studies have indicated that sarcopenia is associated with poor post‐operative outcomes in liver cancer patients, but the studies are limited by confounding from mixed diseases, retrospective data, and non‐standardized measurement methods. At present, there is no research with both muscle mass and strength as predictors for hepatocellular carcinoma (HCC) outcomes. We studied the impact of sarcopenia on post‐operative outcomes in HCC patients in a cohort study designed according to the European Working Group on Sarcopenia in Older People standards. Methods A total of 781 consecutive patients admitted to our centre were registered from May 2020 to August 2021. All participants submitted questionnaires and underwent handgrip strength, chair stand test, physical performance, and computed tomographic evaluation. Then, they were divided into three groups according to muscle mass and strength: Group A (reduced muscle mass and strength), Group B (reduced muscle strength or reduced muscle mass), and Group C (normal muscle mass and strength). The baseline data and post‐operative outcomes were compared and analysed. The primary outcome variable in this study was the presence of a major post‐operative complication, and the secondary outcome was the 90‐day re‐admission rate. Results A total of 155 patients [median age, 60.00 (IQR, 51.00–66.00) years; 20 females (12.90%)] were included after strict exclusion. The mean (SD) BMI was 23.37 ± 0.23 kg/m2. The mean (SD) SMI of all participants was 47.05 ± 0.79 cm2/m2, and the mean (SD) handgrip strength was 32.84 ± 0.69 kg. Among them, 77 (49.68%) patients underwent laparoscopic hepatectomy, and 73 (47.10%) patients received major hepatectomy. Regarding the post‐operative results, Group A had a higher rate of major complications [40.91% (9 of 22) vs. 11.94% (8 of 67) in Group B and 6.06 (4 of 66) in Group C; P = 0.001], higher rate of blood transfusion (77.27% vs. 46.27% in Group B and 42.42% in Group C; P = 0.015), higher hospitalization expenses (P = 0.001), and longer hospital stay (P

Abstract Background Clear cell renal cell carcinoma (ccRCC) is characterized by the accumulation of lipid-reactive oxygen species. Ferroptosis, due to the lipid peroxidation, has been reported to be strongly correlated with tumorigenesis and progression. However, the functions of the ferroptosis process in ccRCC remain unclear. Methods After sample cleaning, data integration, and batch effect removal, we used the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases to screen out the expression and prognostic value of ferroptosis-related lncRNAs and then performed the molecular subtyping using the K-means method. Then, the functional pathway enrichment and immune microenvironment infiltration between the different clusters were carried out. The results showed a significant difference in immune cell infiltration between the two clusters and the associated marker responded to individualized differences in treatment. Then, least absolute shrinkage and selection operator (LASSO) Cox regression was used to establish a prognostic signature based on 5 lncRNAs. This signature could accurately predicted patient prognosis and served as an independent clinical risk factor. We then combined significant clinical parameters in multivariate Cox regression and the prognostic signature to construct a clinical predictive nomogram, which provides appropriate guidance for predicting the overall survival of ccRCC patients. Results The prognostic differentially expressed ferroptosis-related LncRNAs (DEFRlncRNAs) were found, and 5 lncRNAs were finally used to establish the prognostic signature in the TCGA cohort, with subsequently validation in the internal and external cohorts. Moreover, we conducted the molecular subtyping and divided the patients in the TCGA cohort into two clusters showing differences in Hallmark pathways, immune infiltration, immune target expression, and drug therapies. Differences between clusters contributed to individualizing treatment. Furthermore, a nomogram was established to better predict the clinical outcomes of the ccRCC patients. Conclusions Our study conducted molecular subtyping and established a novel predictive signature based on the ferroptosis-related lncRNAs, which contributed to the prognostic prediction and individualizing treatment of ccRCC patients.

Abstract Background To assess the correlation between ocular residual astigmatism and anterior corneal astigmatism in children with low and moderate myopia. Methods Refractive astigmatism was determined by subjective manifest refraction. Anterior corneal astigmatism was determined by IOL Master. Thibos vector analysis was used to calculate ocular residual astigmatism. Correlation analysis was used to assess the relationship between the amounts of ocular residual astigmatism and anterior corneal astigmatism. The relationship between the vectors of ocular residual astigmatism and anterior corneal astigmatism was evaluated by a physical method. Results The study analysed 241 right eyes of 241 children aged 8 to 18 years old. In this study, the median magnitude of ocular residual astigmatism was 1.02 D, with an interquartile range was of 0.58 D. Against-the-rule ocular residual astigmatism was seen in 232 eyes (96.3%). There was a significant and moderate correlation between ocular residual astigmatism and anterior corneal astigmatism (r = 0.50, P

Abstract PF‐05251749 is a dual inhibitor of casein kinase 1 δ/ε under clinical development to treat disruption of circadian rhythm in Alzheimer's and Parkinson's diseases. In vitro, PF‐05251749 (0.3–100 μM) induced CYP3A in cryopreserved human hepatocytes, demonstrating non‐saturable, dose–dependent CYP3A mRNA increases, with induction slopes in the range 0.036–0.39 μM−1. In a multiple‐dose study (B8001002) in healthy participants, CYP3A activity was explored by measuring changes in 4β‐hydroxycholesterol/cholesterol ratio. Following repeated oral administration of PF‐05251749, up to 400 mg q.d., no significant changes were observed in 4β‐hydroxycholesterol/cholesterol ratio; this ratio increased significantly (~1.5‐fold) following administration of PF‐05251749 at 750 mg q.d., suggesting potential CYP3A induction at this dose. Physiologically based pharmacokinetic (PBPK) models were developed to characterize the observed clinical pharmacokinetics (PK) of PF‐05251749 at 400 and 750 mg q.d.; the PBPK induction model was calibrated using the in vitro linear fit induction slope, with rifampin as reference compound (Indmax = 8, EC50 = 0.32 μM). Clinical trial simulation following co‐administration of PF‐05251749, 400 mg q.d. with oral midazolam 2 mg, predicted no significant drug interaction risk. PBPK model predicted weak drug interaction following co‐administration of PF‐05251749, 750 mg q.d. with midazolam 2 mg. In conclusion, good agreement was obtained between CYP3A drug interaction risk predicted using linear‐slope PBPK model and exploratory biomarker trends. This agreement between two orthogonal approaches enabled assessment of drug interaction risks of PF‐05251749 in early clinical development, in the absence of a clinical drug–drug interaction study.

Abstract Background Urethral stricture and reconstruction are one of the thorny difficult problems in the field of urology. The continuous development of tissue engineering and biomaterials has given new therapeutic thinking to this problem. Bacterial cellulose (BC) is an excellent biomaterial due to its accessibility and strong plasticity. Moreover, adipose-derived stem cells (ADSCs) could enhance their wound healing ability through directional modification. Methods First, we used physical drilling and sulfonation in this study to make BC more conducive to cell attachment and degradation. We tested the relevant mechanical properties of these materials. After that, we attached Fibroblast Growth Factor Receptor 2 (FGFR2)-modified ADSCs to the material to construct a urethra for tissue engineering. Afterward, we verified this finding in the male New Zealand rabbit model and carried out immunohistochemical and imaging examinations 1 and 3 months after the operation. At the same time, we detected the potential biological function of FGFR2 by bioinformatics and a cytokine chip. Results The results show that the composite has excellent repairability and that this ability is correlated with angiogenesis. The new composite in this study provides new insight and therapeutic methods for urethral reconstruction. The preliminary mechanism showed that FGFR2 could promote angiogenesis and tissue repair by promoting the secretion of Vascular Endothelial Growth Factor A (VEGFA) from ADSCs. Conclusions Double-modified sulfonated bacterial cellulose scaffolds combined with FGFR2-modified ADSCs provide new sight and treatments for patients with urethral strictures.

Abstract Hydroxylated isoprenoid glycerol dialkyl glycerol tetraethers (OH‐GDGTs) preserved in marine sediments are thought to be controlled by sea surface temperature (SST). However, water depth may also exert a significant influence on OH‐GDGTs. Here, we investigated sedimentary OH‐GDGTs in the Kermadec and Atacama trench regions (2,560–9,560 m water depth). Sedimentary OH‐GDGTs in hadal trenches were dominated by OH‐GDGT‐0 (72 ± 8%), potentially reflecting an adaption of source organisms to ambient cold deep water. This result, combined with global data set, revealed that the predominance of OH‐GDGT‐0 is a ubiquitous phenomenon in deep‐sea sediments, leading to a considerable underestimation of RI‐OH′‐derived SSTs. By considering both SST and water depth effects, we developed more accurate OH‐GDGT‐based paleothermometers for both shallow regions and the global ocean, encompassing the full‐ocean‐depth range. Our findings highlight the importance of accounting for the effect of water depth on OH‐GDGTs and provide improved tools for reconstructing paleo‐SSTs.

BackgroundNon-WNT/non-SHH medulloblastoma (MB) is one of the subtypes with the highest genetic heterogeneity in MB, and its current treatment strategies have unsatisfactory results and significant side effects. As a member of the centromere protein (CENP) family, centromeric protein E (CENPE) is a microtubule plus-end-directed kinetochore protein. Heterozygous mutations in CENPE can leads to primary microcephaly syndrome. It has been reported that CENPE is upregulated in MB, but its role in MB development is still unknown.MethodsWe downloaded the relevant RNA seq data and matched clinical information from the GEO database. Bioinformatics analysis includes differential gene expression analysis, Kaplan-Meier survival analysis, nomogram analysis, ROC curve analysis, immune cell infiltration analysis, and gene function enrichment analysis. Moreover, the effects of CENPE expression on cell proliferation, cell cycle, and p53 signaling pathway of non-WNT/non-SHH MB were validated using CENPE specific siRNA in vitro experiments.ResultsCompared with normal tissues, CENPE was highly expressed in MB tissues and served as an independent prognostic factor for survival in non-WNT/non-SHH MB patients. The nomogram analysis and ROC curve further confirmed these findings. At the same time, immune cell infiltration analysis showed that CENPE may participate in the immune response and tumor microenvironment (TME) of non-WNT/non-SHH MB. In addition, gene enrichment analysis showed that CENPE was closely related to the cell cycle and p53 pathway in non-WNT/non-SHH MB. In vitro experimental validation showed that knockdown of CENPE inhibited cell proliferation by activating the p53 signaling pathway and blocking the cell cycle.ConclusionThe expression of CENPE in non-WNT/non-SHH MB was positively correlated with poor prognosis. CENPE may affect tumor progression by regulating cell cycle, p53 pathway, and immune infiltration. Hence, CENPE is highly likely a novel biomarker and potential therapeutic target for non-WNT/non-SHH MB.

OX40 (CD134), a member of the TNF receptor superfamily, is a widely studied costimulatory immune checkpoint. Several OX40 agonistic antibodies are in the clinical stage for cancer treatment, among which PF-04518600 is the leader and currently in phase II trial. It has been recognized that one potential mode of action for anti-OX40 antibodies is the deletion of intratumoral Tregs. Thus, a novel human anti-OX40 antibody, BAT6026, was generated with enhanced antibody dependent cellular cytotoxicity (ADCC) via fucose deletion to strengthen its Treg depletion activity. This characteristic of BAT6026 differentiates it from other previously reported anti-OX40 antibodies in the field of tumor therapy. The affinity of BT6026 to OX40 was 0.28nM, approximately 8 times stronger than that of PF-04518600. BAT6026 effectively competed for the binding of ligand OX40L to OX40, whereas PF-04518600 only partially competed. Moreover, compared to PF-04518600, BAT6026 activated T cells more effectively when clustered by FcγRs engagement and stimulated SEB-pretreated PBMCs to secrete IL-2 cytokines in vitro. In addition, BAT6026 demonstrated stronger anti-tumor activity than PF-04518600 in an OX40-humanized mouse MC38 tumor model. BAT6026 also showed a significantly synergistic effect on tumor inhibition when combined treatment with PD-1 antibody. Analysis of tumor-infiltrating T cells revealed that BAT6026 treatment significantly reduced Treg cells and increased CD8+ T cells in tumor. Preclinical safety assessment in non-human primates demonstrated a good safety profile for BAT6026. Together these data warrant further development of BAT6026 into clinical trials for patients with cancer.

BackgroundThe amplitude of low-frequency fluctuation (ALFF) is a measure of spontaneous brain activity derived from resting-state functional magnetic resonance imaging (rs-fMRI). Previous research has suggested that abnormal ALFF values may be associated with major depressive disorder (MDD) and suicide attempts in adolescents. In this study, our aim was to investigate the differences in ALFF values between adolescent MDD patients with and without a history of suicide attempts, and to explore the potential utility of ALFF as a neuroimaging biomarker for aiding in the diagnosis and prediction of suicide attempts in this population.MethodsThe study included 34 adolescent depression patients with suicide attempts (SU group), 43 depression patients without suicide attempts (NSU group), and 36 healthy controls (HC group). Depression was diagnosed using a threshold score greater than 17 on the Hamilton Depression Rating Scale (HDRS). The rs-fMRI was employed to calculate zALFF values and compare differences among the groups. Associations between zALFF values in specific brain regions and clinical variables such as emotion regulation difficulties were explored using Pearson partial correlation analysis. Receiver-Operating Characteristics (ROC) analysis assessed the ability of mean zALFF values to differentiate between SU and NSU groups.ResultsSignificant differences in zALFF values were observed in the left and right inferior temporal gyrus (l-ITG, r-ITG) and right fusiform gyrus (r-FG) among the three groups (GRF corrected). Both SU and NSU groups exhibited increased zALFF values in the inferior temporal gyrus compared to the HC group. Furthermore, the SU group showed significantly higher zALFF values in the l-ITG and r-FG compared to both the NSU group and the HC group. Partial correlation analysis revealed a negative correlation between zALFF values in the left superior and middle frontal gyrus (l-SFG, l-MFG) and the degree of emotional dysregulation in the SU group (R = −0.496, p = 0.003; R = −0.484, p = 0.005). Combining zALFF values from the l-ITG and r-FG achieved successful discrimination between depressed adolescents with and without suicide attempts (AUC = 0.855) with high sensitivity (86%) and specificity (71%).ConclusionDepressed adolescents with suicidal behavior exhibit unique neural activity patterns in the inferior temporal gyrus and fusiform gyrus. These findings highlight the potential utility of these specific brain regions as biomarkers for identifying suicide risk in depressed adolescents. Furthermore, associations between emotion dysregulation and activity in their frontal gyrus regions were observed. These findings provide preliminary yet pertinent insights into the pathophysiology of suicide in depressed adolescents.

Background and objectiveCerebrocardiac syndrome (CCS) is a severe complication of severe traumatic brain injury (sTBI) that carries high mortality and disability rates. Early identification of CCS poses a significant clinical challenge. The main objective of this study was to investigate potential risk factors associated with the development of secondary CCS in patients with sTBI. It was hypothesized that elevated right heart Tei index (TI), lower Glasgow Coma Scale (GCS) scores, and elevated cardiac troponin-I (cTnI) levels would independently contribute to the occurrence of CCS in sTBI patients.MethodsA retrospective cohort study was conducted to identify risk factors for CCS secondary to sTBI. One hundred and fifty-five patients were enrolled with sTBI admitted to the hospital between January 2016 and December 2020 and divided them into a CCS group (n = 75) and a non-CCS group (n = 80) based on the presence of CCS. This study involved the analysis and comparison of clinical data from two patient groups, encompassing demographic characteristics, peripheral oxygen saturation (SPO2), neuron-specific enolase (NSE), cardiac troponin-I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), optic nerve sheath diameter (ONSD), cardiac ultrasound, acute physiology and chronic health evaluation (APACHE II) scores, and GCS scores and so on. Multivariate logistic regression was employed to identify independent risk factors for CCS, and receiver operating characteristic (ROC) curves were used to assess their predictive value for CCS secondary to sTBI.ResultsThe study revealed that 48.4% of sTBI patients developed secondary CCS. In the multivariate analysis model 1 that does not include NT-proBNP and cTnI, ONSD (OR = 2.582, 95% CI: 1.054–6.327, P = 0.038), right heart Tei index (OR = 2.81, 95% CI: 1.288–6.129, P = 0.009), and GCS (OR = 0.212, 95% CI: 0.086–0.521, P = 0.001) were independent risk factors for secondary CCS in sTBI patients. In multivariate analysis model 2 that includes NT-proBNP and cTnI, cTnI (OR = 27.711, 95%CI: 3.086–248.795, P = 0.003), right heart Tei index (OR = 2.736, 95% CI: 1.056–7.091, P = 0.038), and GCS (OR = 0.147, 95% CI: 0.045–0.481, P = 0.002) were independent risk factors for secondary CCS in sTBI patients. The area under the ROC curve for ONSD, Tei index, GCS, and cTnI were 0.596, 0.613, 0.635, and 0.881, respectively. ONSD exhibited a positive predictive value (PPV) of 0.704 and a negative predictive value (NPV) of 0.634. The Tei index demonstrated a PPV of 0.624 and an NPV of 0.726, while GCS had a PPV of 0.644 and an NPV of 0.815. On the other hand, cTnI exhibited a significantly higher PPV of 0.936 and an NPV of 0.817. These findings indicate that the Tei index, GCS score, and cTnI possess certain predictive value for secondary CCS in patients with sTBI.ConclusionsThe study provides valuable insights into the identification of independent risk factors for CCS secondary to sTBI. The findings highlight the significance of right heart Tei index, GCS score, and cTnI as potential predictive factors for CCS in sTBI patients. Further larger-scale studies are warranted to corroborate these findings and to provide robust evidence for the development of early intervention strategies aimed at reducing the incidence of CCS in this patient population.

Introduction: Data from acute ischemic stroke patients throughout 2021 from one district of an archipelago city of China were collected and analyzed retrospectively to determine the management difference due to time lags from onset of symptoms to the arrival at the stroke center (FMCT) of two regions: main island (MI) and outer islets (OIs). Methods: All patients information from 1 January to 31 December 2021 was retrieved through the electronic medical records system of the only stroke center in MI. After screening and exclusion, each patient's medical record was reviewed by two neurologists separately. Before OI patients were allocated to a group, their residential addresses at onset of the stroke were confirmed by telephone. Comparisons were analyzed between the two regions for gender, age, pre-stroke risk factors and peri-admission management parameters. Results: A total of 326 patients met the inclusion criteria: 300 from the MI group and 26 for the OI group. Intergroup comparisons for gender, age and most of the risk factors showed no significant difference. FMCT were shown to be significantly distinct (p

Osteoarthritis (OA) is a degenerative disease that causes severe pain and reduces the range of motion of the joint, decreasing the quality of life for millions of individuals in the United States. Electromyography (EMG) sensors have been widely studied in biomechanics, showing applications in prosthetics, robotics, and control. While complex musculoskeletal models have been well established, the attempt of directly correlating EMG with kinematics and kinetics is still quite limited. Particularly, little work has been conducted on OA patients. In this work, we propose a method for estimating lower body joint angles (JAs) and ground reaction forces (GRFs) from surface-EMG sensors during a step-down task for individuals diagnosed with OA. The JAs and GRFs were measured by a Vicon motion capture system and force plates, respectively. EMG, JAs, and GRFs were used to train an echo state network (ESN) which afforded JAs with relative errors of 3.78% and 3.71% and the GRFs with relative errors of 3.619% and 4.596% for training and testing datasets, respectively. This study suggests the high fidelity of the ESN in automatically predicting full lower body kinematics and kinetics from the EMG signals. The results of this work promote the development of an EMG-controlled lower limb rehabilitation robot system for patients with OA.

Metasurface has garnered extensive attention across multiple disciplines owing to its profound capability in electromagnetic (EM) manipulations. To determine its EM characteristics accurately, full-wave simulations are essential. These simulations necessitate significant amounts of time and memory resources, hindering the efficiency of the design process. In this article, we propose MetaPhyNet, a novel physics-driven neural network based on temporal coupled-mode theory (CMT) to address the challenges of low efficiency and high memory consumption in large-scale metasurface design. In the proposed approach, a surrogate model is developed to achieve rapid prediction of the EM responses of ultra-large-scale metasurfaces. In comparison with the full-wave EM simulation, the proposed model reduces the simulation time of the ultra-large-scale metasurface by up to two orders of magnitude and the memory consumption by more than two orders of magnitude. Our proposed approach aims to enhance the efficiency and intelligence in metasurface design by leveraging the principles of CMT within a neural network framework. Through this innovative integration of physics-based modeling and machine learning, we seek to achieve significant advancements in the design efficiency of metasurfaces. We apply the proposed model to optimize the design of two metasurface absorbers to showcase the effectiveness of our proposed approach. Simulations and experimental results are provided to demonstrate the value and impact of our approach in addressing existing challenges in full-wave EM simulation-based design optimizations of metasurfaces.

Borosilicate bioactive glasses exhibit excellent bioactivity and degradation properties; however, they suffer from the rapid release of bioactive elements at the initial stage of their degradation. Excessive local concentrations (such as those of B) can affect cell proliferation. Moreover, the degradation and mineralization ability of these glasses deteriorate at the later stages. Aiming to balance the release of bioactive elements during the whole process, herein, a borosilicate bioactive glass 18SiO2–6Na2O–8K2O–8MgO–22CaO–2P2O5–36B2O3 (mol%) was prepared using the melting method. Further, the effects of microcrystallization on the release of bioactive elements and in vitro degradation were studied. Results show that after heat treatment at temperatures over 620 °C, multiple microcrystalline phases, including Ca2SiO4, CaB2O4, and CaMgB2O5, form in the glass. The glass samples heat-treated within the range of 620–640 °C undergo appropriate devitrification degrees, decelerating the rate of pH increase of the immersion solution during the initial stage in comparison to those treated at lower temperatures. This results in a more continuous release of all bioactive elements and allows better control of the overall degradation. Contrarily, the more extensive devitrification degrees of glass samples heat-treated at higher temperatures reverse the pH increase and degradation trends. Since bone marrow mesenchymal stem cells and mouse embryonic osteoblast cells are pH-sensitive, inducing a suitable degree of devitrification proved to favor cell viability and enhance the mineralization capacity. Thus, different microcrystallization degrees provide new approaches for controlling the degradation and release of bioactive elements, resulting in the simultaneous enhancement of biosafety and bioactivity.

Abstract Objective Ying Yang1 (YY1) has already been discussed in oral squamous cell carcinoma (OSCC), but the knowledge about its mediation on long non-coding RNA KCNQ1 overlapping transcript 1/microRNA-506-3p/synaptophysin like 1 (Kcnq1ot/miR-506-3p/SYPL1) axis in OSCC is still in its infancy. Hence, this article aims to explain the mechanism of YY1/Kcnq1ot1/miR-506-3p/SYPL1 axis in OSCC development. Methods YY1, Kcnq1ot1, miR-506-3p and SYPL1 expression levels were determined in OSCC tissues. The potential relation among YY1, Kcnq1ot1, miR-506-3p and SYPL1 was explored. Cell progression was observed to figure out the actions of depleted YY1, Kcnq1ot1 and SYPL1 and restored miR-506-3p in OSCC. OSCC tumorigenic ability in mice was examined. Results Elevated YY1, Kcnq1ot1 and SYPL1 and reduced miR-506-3p were manifested in OSCC. YY1 promoted Kcnq1ot1 transcription and up-regulated Kcnq1ot1 expression, thereby promoting OSCC cell procession. Silencing Kcnq1ot1 or elevating miR-506-3p delayed OSCC cell progression and silencing Kcnq1ot1 impeded tumorigenic ability of OSCC cells in mice. YY1-mediated Kcnq1ot1 sponged miR-506-3p to target SYPL1. Conclusion YY1 promotes OSCC cell progression via up-regulating Kcnq1ot1 to sponge miR-506-3p to elevate SYPL1, guiding a novel way to treat OSCC.

Bacillus thuringiensis toxin Cry5Ba triggers potassium ion leakage, causing mitochondrial damage and energy imbalance. C. elegans can monitor this intracellular energy imbalance via AMP-activated protein kinase to trigger innate immune responses.

Abstract Inner ear disorders are a cluster of diseases that cause hearing loss in more than 1.5 billion people worldwide. However, the presence of the blood-labyrinth barrier (BLB) on the surface of the inner ear capillaries greatly hinders the effectiveness of systemic drugs for prevention and intervention due to the low permeability, which restricts the entry of most drug compounds from the bloodstream into the inner ear tissue. Here, we report the finding of a novel receptor, low-density lipoprotein receptor-related protein 1 (LRP1), that is expressed on the BLB, as a potential target for shuttling therapeutics across this barrier. As a proof-of-concept, we developed an LRP1-binding peptide, IETP2, and covalently conjugated a series of model small-molecule compounds to it, including potential drugs and imaging agents. All compounds were successfully delivered into the inner ear and inner ear lymph, indicating that targeting the receptor LRP1 is a promising strategy to enhance the permeability of the BLB. The discovery of the receptor LRP1 will illuminate developing strategies for crossing the BLB and for improving systemic drug delivery for inner ear disorders.

Antitumor activity of CD8+ T cells is potentially restrained by a variety of negative regulatory pathways that are triggered in the tumor microenvironment, yet, the exact mechanisms remain incompletely defined. Here, we report that intrinsic RIG-I in CD8+ T cells represents such a factor, as evidenced by observations that the tumor-restricting effect of endogenous or adoptively transferred CD8+ T cells was enhanced by intrinsic Rig-I deficiency or inhibition, with the increased accumulation, survival, and cytotoxicity of tumor-infiltrating CD8+ T cells. Mechanistically, T cell activation–induced RIG-I upregulation restrained STAT5 activation via competitive sequestering of HSP90. In accordance with this, the frequency of RIG-I+ tumor-infiltrating CD8+ T cells in human colon cancer positively correlated with attenuated survival and effector signatures of CD8+ T cells as well as poor prognosis. Collectively, these results implicate RIG-I as a potentially druggable factor for improving CD8+ T cell–based tumor immunotherapy.

The nasal mucosa is the first barrier to pathogen invasion through the respiratory tract. Few studies have focused on nasal resistance to invasion by respiratory pathogens due to the lack of models related to the nasal mucosa. Hence, it is necessary to construct a nasal mucosal model to study host-pathogen interactions. We established a long-term in vitro sheep nasal mucosa explant model (NMEM), which exhibited typical epithelial cilia and epithelial proliferation ability within 11 days. Moreover, to evaluate whether the NMEM was suited for in vitro pathogenic study, we used pseudorabies virus (PRV) and showed that it successfully infected and produced severe lesions in the NMEM, particularly interferon (IFN)-stimulated gene product 15 (ISG15). IFN decreased significantly after the PRV infection. Similarly, we used this NMEM model to screen several antiviral substances, such as probiotics and drugs. A previous study showed that nasal commensal bacteria, particularly Bacillus subtilis, had high antiviral activity. Then, we used the NMEM to evaluate six sheep-derived B. subtilis strains and demonstrated that it significantly induced the production of IFN and expression of ISG15. The sheep-derived B. subtilis was pretreated with the sheep NMEM before the PRV infection to evaluate the antiviral effect. The results showed that NSV2 significantly inhibited infection by PRV and reduced the viral load (p

ABSTRACT: The gamma-coronavirus infectious bronchitis virus (IBV) has a high mutation rate and mainly invades the respiratory mucosa, making it difficult to prevent and causing great economic losses. Nonstructural protein 16 (NSP16) of IBV QX also not only plays an indispensable role in virus invading but also might hugely influence the antigen's recognition and presentation ability of host BMDCs. Hence, our study tries to illustrate the underline mechanism of how NSP16 influences the immune function of BMDCs. Initially, we found that NSP16 of the QX strain significantly inhibited the antigen presentation ability and immune response of mouse BMDCs, which was stimulated by Poly (I:C) or AIV RNA. Besides mouse BMDCs, we also found that NSP16 of the QX strain also significantly stimulated the chicken BMDCs to activate the interferon signaling pathway. Furthermore, we preliminarily demonstrated that IBV QX NSP16 inhibits the antiviral system by affecting the antigen-presenting function of BMDCs.

Litter decomposition is an essential process in nutrient cycling in terrestrial ecosystems. Phenolic acids have an allelopathic effect on the natural regeneration of rhododendron forests, which was recently observed in rhododendron forests in Southwest China. We investigated the distribution of phenolic acids and their relationship with soil nutrients during litter decomposition to provide a reference for the subsequent artificial management of rhododendron forests. High-performance liquid chromatography (HPLC) was used to analyze the contents of six phenolic acids in the litter layer, humus layer, and soil layer during litter decomposition. During the first 3 three months, the rapid decomposition of the litter from two early flowering rhododendron species released large amounts of phenolic acids, and the lower litter layer decomposed rapidly. In addition, the total phenolic acid content in the litter decreased by 257.60 μg/g (Rhododendron siderophyllum) and 53.12 μg/g (Rhododendron annae) in the first three 3 months. During subsequent litter decomposition, the protocatechuic acid content in the litters of Rhododendron siderophyllum ranged from 20.15 μg/g to 39.12 μg/g, and the ferulic acid content was 10.70 μg/g to –33.79 μg/g. The protocatechuic acid and ferulic acid contents in the litter of Rhododendron annae were in the ranges of 10.88—19.68 μg/g and 10.75—18.00 μg/g, respectively. The contents of these two phenolic acids and the trend of decomposition were different from those of gallic acid, chlorogenic acid, caffeic acid and syringic acid. The distribution of phenolic acids was influenced by soil organic matter (SOM), soil ammonium nitrogen (NH4+), soil nitrate nitrogen (NO3–) and soil available phosphorus (AP). The results indicate seasonal variations in phenolic acid release during litter decomposition. The amount of phenolic acid in the litter decreased after 18 months of decomposition, but it returned to the previous level in the soil and the humus after different trends. More research into the metabolism of phenolic acids is needed.

Abstract This study analyzes up‐to‐date gravity data in the Galapagos triple junction region to understand crustal structure and melt distribution beneath the propagating Cocos‐Nazca spreading center (CNSC). Application of a standard thermal model to the mantle Bouguer gravity anomaly (MBA) does not appear to result in a realistic crustal thickness in this region. The cross‐CNSC MBA profiles flatten and axial values increase from east toward the western end of the CNSC. A simple smoothing filter applied to the standard thermal model with different filter widths can explain the progressive flattening of the MBA and is interpreted as different distribution widths (concentrations) of partial melt in the mantle. The east‐west residual MBA gradient along the CNSC is similar to the east flank of the East Pacific Rise (EPR), suggesting that the along‐CNSC gradient could partly reflect the shallow mantle properties associated with the EPR.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that has become more prevalent in recent years. Environmental endocrine disruptor bisphenol A (BPA) has been linked to ASD. BPA analogues (BPs) are structure-modified substitutes widely used as safer alternatives in consumer products, yet few studies have explored the developmental neurotoxicity (DNT) of BPA analogues. In the present study, we used the larval zebrafish model to assess the DNT effects of BPA and its analogues. Our results showed that many BPA analogues are more toxic than BPA in the embryonic zebrafish assay regarding teratogenic effect and mortality, which may partially due to differences in lipophilicity and/or different substitutes of structural function groups such as CF3, benzene, or cyclohexane. At sublethal concentrations, zebrafish embryos exposed to BPA or BPs also displayed reduced prosocial behavior in later larval development, evidenced by increased nearest neighbor distance (NND) and the interindividual distance (IID) in shoaling, which appears to be structurally independent. An in-depth analysis of BPA, bisphenol F (BPF), and bisphenol S (BPS) revealed macrocephaly and ASD-like behavioral deficits resulting from exposures to sublethal concentrations of these chemicals. The ASD-like behavioral deficits were characterized by hyperactivity, increased anxiety-like behavior, and decreased social contact. Mechanistically, accelerated neurogenesis that manifested by increased cell proliferation, the proportion of newborn mature neurons, and the number of neural stem cells in proliferation, as well as upregulated genes related to the K+ channels, may have contributed to the observed ASD-like morphological and behavioral alterations. Our findings indicate that BPF and BPS may also pose significant risks to ASD development in humans and highlight the importance of a comprehensive assessment of DNT effects for all BPA analogues in the future.

Recombinant human interferon α2b (rhIFNα2b) is widely used as an antiviral therapy agent for the treatment of hepatitis B and hepatitis C. The current identification test for rhIFNα2b is complex. In this study, an anti-rhIFNα2b nanobody was discovered and used for the development of a rapid lateral flow strip for the identification of rhIFNα2b. RhIFNα2b was used to immunize an alpaca, which established a phage nanobody library. After five steps of enrichment, the nanobody I22, which specifically bound rhIFNα2b, was isolated and inserted into the prokaryotic expression vector pET28a. After subsequent purification, the physicochemical properties of the nanobody were determined. A semiquantitative detection and rapid identification assay of rhIFNα2b was developed using this novel nanobody. To develop a rapid test, the nanobody I22 was coupled with a colloidal gold to produce lateral-flow test strips. The developed rhIFNα2b detection assay had a limit of detection of 1 μg/mL. The isolation of I22 and successful construction of a lateral-flow immunochromatographic test strip demonstrated the feasibility of performing ligand-binding assays on a lateral-flow test strip using recombinant protein products. The principle of this novel assay is generally applicable for the rapid testing of other commercial products, with a great potential for routine use in detecting counterfeit recombinant protein products.

Renewable energy has become an important choice to solve the energy crisis and environmental problems. A sustainable development needs policies and strategies policies, which can improve energy efficiency and reduce greenhouse gas emissions. By collecting the research results released by relevant statistical departments and authoritative institutions, this paper summarizes the international energy development situation, systematically combs the energy development situation of the European Union, United States, Australia, India, Brazil. The development trend of wind, solar, biomass, geothermal, ocean, and hydrogen energy have been analyzed. In addition, this paper proposes that China should draw up its own development path of renewable energy from international development experience, and actively explore renewable energy policies and strategies adapted to different stages of development.

This work analyzed the Ms 7.1 earthquake occurred at 01:47 UT on September 8th, 2021, in Acapulco City, Guerrero, Mexico (17.12° N, 99.6° W, N and W represent north and west, respectively) with a 30 ​km focal depth by using multiple parameters recorded by China Seismo-Electromagnetic Satellite-1 (CSES-1). In this work, we studied the electron density (Ne) recorded by langmuir probe and O+ from plasma analyzer package at a height of 507 ​km 15 days before the earthquake. After excluding the plasma density variations caused by the geomagnetic storms on August 28th and September 7th, the results revealed that the nighttime Ne, and O+ increased on September 2nd (6 days before the earthquake) simultaneously within ±10° in latitude and ±10° in longitude around the epicenter. In addition, the enhancement was also found in electron density profile (EDP) between 200 ​km and 300 ​km derived from GNSS radio occultation data. Not only the different particle species (Ne and O+) at 507 ​km, but also electron density at 507 ​km and EDP in lower ionosphere shown anomalies 6 days before the earthquake. Basing on the results, we suggest that the enhancements of Ne, O+, and EDP on September 2nd are possible related to the Mexico Ms 7.1 earthquake on September 8th.

Abstracts: This work analyzed the electromagnetic field (EM) anomalies recorded by the electric field detector (EFD) and the search coil magnetometer (SCM) onboard the China Seismo-Electromagnetic Satellite (CSES) during the two earthquakes (EQ), which are the Yangbi Ms6.4 EQ on May 21 (China Standard Time, CST) and the Madoi Ms7.4 EQ on May 22 (CST), 2021. These two EQs successively occurred in West China. The prevailing frequency band excluding the interferences from the satellite platform was chosen to extract convincible seismic-related EM disturbances. Two criteria were put forward to obtain reliable precursors using the Kp and Dst index and the variation rate of Dst per hour to eliminate the tinier spatial perturbations. We found that the seismic-related EM disturbances mainly appeared 1–10 days before the two earthquakes within the spatial extension of 1000 ​km above the epicenters.

The molecular classification and tumour microenvironment in intrahepatic cholangiocarcinoma (iCCA) need further characterisation. Here, the authors perform single cell RNA-sequencing from 14 pairs of iCCA tumours and non-tumour liver tissues and propose S100P and SPP1 as markers for patient classification.

To address the challenges of complex backgrounds, small defect sizes, and diverse defect types in defect detection of wire bonding X-ray images, this paper proposes a convolutional-neural-network-based defect detection method called YOLO-CSS. This method designs a novel feature extraction network that effectively captures semantic features from different gradient information. It utilizes a self-adaptive weighted multi-scale feature fusion module called SMA which adaptively weights the contribution of detection results based on different scales of feature maps. Simultaneously, skip connections are employed at the bottleneck of the network to ensure the integrity of feature information. Experimental results demonstrate that on the wire bonding X-ray defect image dataset, the proposed algorithm achieves mAP 0.5 and mAP 0.5–0.95 values of 97.3% and 72.1%, respectively, surpassing the YOLO series algorithms. It also exhibits certain advantages in terms of model size and detection speed, effectively balancing detection accuracy and speed.