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In present work, non-isothermal crystallization behavior for novel Cr50Fe6Co7Mo14C15B6Y2 metallic glass (MG) with super high content of Cr and excellent merits was investigated by differential scanning calorimeter and X-ray diffraction. Both of the Kissinger and Ozawa methods show that the present glass transition is much harder than other transitions for a much larger apparent activation energy (E). While, the growth process of present second crystallization event is the easiest process, since it possesses the smallest E. Meanwhile, the local activation energy established by Kissinger-Akahira-Sunose and Ozawa-Flynn-Wall methods both exhibit a trend of increasing to the maximum value at first and then gradual decrease until the finish of the crystallization, indicating that the difficulty increases until to the maximum at first and then gradually decreases during crystallization. Moreover, all the local Avrami exponent n(x) possesses a value of about 0 < n(x)

Background: Inflammatory responses influence the outcome of immunotherapy and tumorigenesis by modulating host immunity. However, systematic inflammatory response assessment models for predicting cancer immunotherapy (CIT) responses and survival across human cancers remain unexplored. Here, we investigated an inflammatory response score model to predict CIT responses and patient survival in a pan-cancer analysis. Methods: We retrieved 12 CIT response gene expression datasets from the Gene Expression Omnibus database (GSE78220, GSE19423, GSE100797, GSE126044, GSE35640, GSE67501, GSE115821 and GSE168204), Tumor Immune Dysfunction and Exclusion database (PRJEB23709, PRJEB25780 and phs000452.v2.p1), European Genome-phenome Archive database (EGAD00001005738), and IMvigor210 cohort. The tumor samples from six cancers types: metastatic urothelial cancer, metastatic melanoma, gastric cancer, primary bladder cancer, renal cell carcinoma, and non-small cell lung cancer.We further established a binary classification model to predict CIT responses using the least absolute shrinkage and selection operator (LASSO) computational algorithm. Findings: The model had high predictive accuracy in both the training and validation cohorts. During sub-group analysis, area under the curve (AUC) values of 0.82, 0.80, 0.71, 0.7, 0.67, and 0.64 were obtained for the non-small cell lung cancer, gastric cancer, metastatic urothelial cancer, primary bladder cancer, metastatic melanoma, and renal cell carcinoma cohorts, respectively. CIT response rates were higher in the high-scoring training cohort subjects (51%) than the low-scoring subjects (27%). The five-year survival rates in the high- and low score groups of the training cohorts were 62% and 21%, respectively, while those of the validation cohorts were 54% and 22%, respectively (P

Abstract This prospective, non-randomized, comparative study aimed to compare the visual outcomes and patient satisfaction after implantations of three presbyopia-correcting intraocular lenses (IOLs) after myopic refractive surgery. It was conducted from January 2020 to December 2021 in Shanghai Heping Eye Hospital. Patients were divided into three groups based on the type of IOL implanted. The visual acuity, refractive stability, high-order aberrations, objective visual quality, spectacle independence, and visual function index 14 questionnaire scores of the three groups were compared. This study included 78 eyes of 39 patients: 26 eyes with 839MP, 26 eyes with MF30, and 26 eyes with ZXR00. Uncorrected distance visual acuity improved significantly for all three groups. For a pupil diameter of 4.0 mm, the spherical aberrations of the three groups were 0.33 ± 0.16 μ, 0.50 ± 0.08 μ, and 0.39 ± 0.10 μ, respectively. The spectacle independence for distance vision was over 90% in each group; for near vision, it was only 25% for the ZXR00 group. All three types of presbyopia-correcting IOLs improved visual quality in post-LASIK or PRK patients. However, the high incidence of photic phenomena after presbyopia-correcting IOL implantation in patients who have undergone myopic LASIK should not be neglected.

ABSTRACT Carbapenem-resistant Acinetobacter baumannii (CRAB) poses a significant threat to hospitalized patients as effective therapeutic options are scarce. Based on the genomic characteristics of the CRAB strain AB2877 harboring chromosome-borne blaOXA-23, which was isolated from the bronchoalveolar lavage fluid (BALF) of a patient in a respiratory intensive care unit (RICU), we systematically analyzed antibiotic resistance genes (ARGs) and the genetic context associated with ARGs carried by CRAB strains harboring chromosome-borne blaOXA-23 worldwide. Besides blaOXA-23, other ARGs were detected on the chromosome of the CRAB strain AB2877 belonging to ST208/1806 (Oxford MLST scheme). Several key genetic contexts associated with the ARGs were identified on the chromosome of the CRAB strain AB2877, including (1) the MDR region associated with blaOXA-23, tet(B)-tetR(B), aph(3'')-Ib, and aph(6)-Id (2); the resistance island AbGRI3 harboring armA and mph(E)-msr(E) (3); the Tn3-like composite transposon containing blaTEM-1D and aph(3')-Ia; and (4) the structure “ISAba1-blaADC-25.” The first two genetic contexts were most common in ST195/1816, followed by ST208/1806. The last two genetic contexts were found most frequently in ST208/1806, followed by ST195/1816.IMPORTANCEThe blaOXA-23 gene can be carried by plasmid or chromosome, facilitating horizontal genetic transfer and increasing carbapenem resistance in healthcare settings. In this study, we focused on the genomic characteristics of CRAB strains harboring the chromosome-borne blaOXA-23 gene, and the important genetic contexts associated with blaOXA-23 and other ARGs were identified, and their prevalent clones worldwide were determined. Notably, although the predominant clonal CRAB lineages worldwide containing the MDR region associated with blaOXA-23, tet(B)-tetR(B), aph(3'')-Ib, and aph (6)-Id was ST195/1816, followed by ST208/1806, the CRAB strain AB2877 in our study belonged to ST208/1806. Our findings contribute to the knowledge regarding the dissemination of CRAB strains and the control of nosocomial infection.

Streptococcus agalactiae (Strep. agalactiae) is bovine mastitis pathogen and has thus became a matter of concern to dairy farms worldwide in terms of economic loss. The aims of this study were to (a) determine virulence genes, and (b) characterize the antimicrobial resistance (AMR) profiles and AMR genes and (c) figure out the relationship between AMR phenotypes and genotypes of Strep. agalactiae isolated from dairy cows in north China. A total of 20 virulence genes and 23 AMR genes of 140 isolates collected from 12 farms in six provinces were studied. The antimicrobial susceptibility of 10 veterinary commonly used antimicrobials were tested using the broth microdilution method. Results showed that all the isolates harbored the virulence genes lacIV, gapC, and dltA. The isolates that harbored the genes lacIII, fbsA, hylB, and cfb exhibited the high prevalence (99.29%), followed by isolates that harbored lacI (98.57%), bibA (97.86%), cylE (97.14%), lacII (92.14%), cspA (52.14%), pavA (25%), bca (2.14%), and scpB (0.71%). The fbsB, lmb, spbI, bac, and rib genes were not detected. The virulence patterns of B (fbsA_cfb_cylE_ hylB_bibA_cspA_ gapC_dltA_lacIII/IV) and C (fbsA_cfb_ bibA _ gapC_ dltA_lacIV) were dominant, accounting for 97.86% of the isolates. The following AMR genes were prevalent: pbp1A (97.14%), tet(M) (95.00%), lnu (A) (80.71%), erm (B) (75.00%), tet(O) (72.14%), blaZ (49.29%), tet(S) (29.29%), blaTEM (25.71%), erm (A) (17.14%), erm (C) (13.57%), tet (L) (10.71%), linB (2.86%), and erm (TR) (2.86%). The pbp2b, mecA1, mecC, lnu (D), erm (F/G/Q), and mef (A) genes were not detected. Eighty percent of the isolates harbored AMR genes and were highly resistant to tetracycline, followed by macrolides (10.71%), lincosamides (9.29%) and β-lactams (4.29%). In conclusion, isolates only exhibited well correlation between tetracyclines resistance phenotype and genotype, and almost all isolates harbored intact combination of virulence genes.

A1 polarization of astrocytes mediated prolonged inflammation contributing to brain injury in ischemic stroke. We have previously shown that AD16 protects against neonatal hypoxic-ischemic brain damage in vivo and oxygen-glucose deprivation in vitro. More recently, AD16 has demonstrated safety, tolerability, and favorable pharmacokinetics in a randomized controlled phase I trial. In this study, we utilized a rat model of transient middle cerebral artery occlusion (tMCAO) to explore whether the anti-inflammatory compound AD16 protects against ischemic brain injury by regulating A1 polarization and its underlying mechanisms. Our results showed that AD16 treatment significantly reduced the brain infarcted volume and improved neurological function in tMCAO rats. GO analysis results show that differential genes among the Sham, tMCAO and AD16 treatment groups are involved in the regulation of cytokine and inflammatory response. KEGG enrichment pathways analysis mainly enriched in cytokine-cytokine receptor interaction, viral protein interaction with cytokine-cytokine receptor, TNF, chemokine, NF-κB and IL-17 signaling pathway. Furthermore, AD16 treatment decreased the permeability of the blood-brain barrier and suppressed neuroinflammation. AD16 treatment also significantly reduced the polarization of A1 and inhibited NF-κB and JAK2/STAT3 signaling pathways. This study demonstrates that AD16 protects against brain injury in ischemic stroke by reducing A1 polarization to suppress neuroinflammation through downregulating NF-κB and JAK2/STAT3 signaling. Our findings uncover a potential molecular mechanism for AD16 and suggest that AD16 holds promising therapeutic potential against cerebral ischemia.

ABSTRACT: The H9N2 subtype of the avian influenza virus (AIV) is widely prevalent in birds, threatening the poultry industry and providing genetic material for emerging human pathogens. The prevalence and genetic characteristics of H9N2 in Yunnan Province, China, are largely unknown. Samples were collected from live poultry markets (LPMs) and breeding farms in Yunnan Province. H9N2-positive samples were identified by polymerase chain reaction (PCR), with a high positivity rate of 42.86% in tissue samples. The positivity rate of swab samples in the LPMs in Kunming was 3.97% (17/564), but no AIV was detected in samples from poultry farms in Lijiang, Wenshan, and Yuxi. Evolutionary analysis and genotyping were performed for the 17 strains of isolated H9N2 virus. Phylogenetic analysis revealed that all H9N2 viral genes had 91.6%–100% nucleotide homology, belonged to the G57 genotype, and had high homology with H9N2 viruses isolated from Guangdong and Guangxi, suggesting that the H9N2 viruses in Yunnan Province may have been imported by chicks. Using a nucleotide divergence cutoff of 95%, we identified ten distinct H9N2 genotypes that continued to evolve. The surface genes of the H9N2 isolates displayed substantial genetic diversity, highlighting the genetic diversity and complexity of the H9N2-subtype AIVs in Yunnan. Molecular analysis demonstrated that all 17 strains of H9N2 isolates had mutations at H183N, Q226L, L31P, and I268V in hemagglutinin; S31N in matrix protein 2; and no replacements at positions 274 and 292 of the neuraminidase protein. Sixteen strains had the A558V mutation and one strain had the E627V mutation in polymerase basic protein 2. Analysis of these amino acid sites suggests that H9N2 influenza viruses in Yunnan continue to mutate and adapt to mammals and are sensitive to neuraminidase inhibitors but resistant to adamantanes. It is necessary to strengthen surveillance of AIV H9N2 subtypes in poultry and LPMs in Yunnan to further understand their genetic diversity.

ABSTRACT: Objectives: This study reports the whole-genome sequences of two strains of extended-spectrum beta-lactamase (ESBL)-producing and multidrug-resistant (MDR) K. pneumoniae ST268 and explores their acquired antibiotic resistance genes (ARGs) and the mobile genetic elements (MGEs). Methods: Two strains of K. pneumoniae ST268 were isolated from different samples of one patient. Assessment of antimicrobial susceptibility was performed, and then whole-genome sequencing was conducted. Acquired ARGs, insertion sequences, and transposons harboured by the two strains of K. pneumoniae ST268 were identified, and then the genetic contexts associated with the ARGs were analysed systematically. Results: Two strains of K. pneumoniae ST268 were found to carry the 118.6-kb hybrid IncFIIK:IncQ1:repBR1701 plasmid. All the acquired ARGs carried by the IncF plasmid were found to be situated on the 25.3-kb MDR region bracketed by ISKpn19 and IS26, which was widely present in the plasmids in 14 STs of strains in K. pneumoniae but also in IncF plasmids from Shigella flexneri and Klebsiella quasipneumoniae. Notably, the IncF plasmids harbouring the 25.3-kb MDR region were geographically distributed mainly in China, and the pKP161637-1/pKP160802-1 in our study was the first report on the IncF plasmid carrying the 25.3-kb MDR region bracketed in K. pneumoniae ST268. Conclusions: Two strains of ESBL-producing K. pneumoniae ST268 with a MDR IncF plasmid were identified in a hospital in China. The ARGs were identified on the 25.3-kb MDR region, bracketed by ISKpn19 and IS26, of the IncF plasmids, which were present not only in the K. pneumoniae but also in the S. flexneri and K. quasipneumoniae.

Introduction:Bacillus licheniformis (B.licheniformis) was widely used in poultry feeds. However, it is still unclear about how B.licheniformis regulates the growth and development of Pekin ducks.Methods: The experiment was designed to clarify the effect and molecular mechanism of B. licheniformis on the lipid metabolism and developmental growth of Pekin ducks through multiomics analysis, including transcriptomic and metabolomic analyses.Results: The results showed that compared with the control group, the addition of 400 mg/kg B. licheniformis could significantly increase the body weight of Pekin ducks and the content of triglyceride (p < 0.05), at the same time, the addition of B. licheniformis could affect the lipid metabolism of liver in Pekin ducks, and the addition of 400 mg/kg B. licheniformis could significantly increase the content of lipoprotein lipase in liver of Pekin ducks. Transcriptomic analysis revealed that the addition of B. licheniformis primarily impacted fatty acid and glutathione, amino acid metabolism, fatty acid degradation, as well as biosynthesis and elongation of unsaturated fatty acids. Metabolomic analysis indicated that B. licheniformis primarily affected the regulation of glycerol phospholipids, fatty acids, and glycerol metabolites. Multiomics analysis demonstrated that the addition of B. licheniformis to the diet of Pekin ducks enhanced the regulation of enzymes involved in fat synthesis via the PPAR signaling pathway, actively participating in fat synthesis and fatty acid transport.Discussion: We found that B. licheniformis effectively influences fat content and lipid metabolism by modulating lipid metabolism-associated enzymes in the liver. Ultimately, this study contributes to our understanding of how B. licheniformis can improve the growth performance of Pekin ducks, particularly in terms of fat deposition, thereby providing a theoretical foundation for its practical application.Conclusion:B. licheniformis can increase the regulation of enzymes related to fat synthesis through PPAR signal pathway, and actively participate in liver fat synthesis and fatty acid transport, thus changing the lipid metabolism of Pekin ducks, mainly in the regulation of glycerol phospholipids, fatty acids and glycerol lipid metabolites.

IntroductionThrough the combined use of two nitrification inhibitors, Dicyandiamide (DCD) and chlorate with nitrogen amendment, this study aimed to investigate the contribution of comammox Nitrospira clade B, ammonia oxidizing bacteria (AOB) and archaea (AOA) to nitrification in a high fertility grassland soil, in a 90-day incubation study.MethodsThe soil was treated with nitrogen (N) at three levels: 0 mg-N kg-1 soil, 50 mg-N kg-1 soil, and 700 mg-N kg-1 soil, with or without the two nitrification inhibitors. The abundance of comammox Nitrospira, AOA, AOB, and nitrite oxidising bacteria (NOB) was measured using qPCR. The comammox Nitrospira community structure was assessed using Illumina sequencing.Results and DiscussionThe results showed that the application of chlorate inhibited the oxidation of both NH4+ and NO2- in all three nitrogen treatments. The application of chlorate significantly reduced the abundance of comammox Nitrospira amoA and nxrB genes across the 90-day experimental period. Chlorate also had a significant effect on the beta diversity (Bray-Curtis dissimilarity) of the comammox Nitrospira clade B community. Whilst AOB grew in response to the N substrate additions and were inhibited by both inhibitors, AOA showed litle or no response to either the N substrate or inhibitor treatments. In contrast, comammox Nitrospira clade B were inhibited by the high ammonium concentrations released from the urine substrates. These results demonstrate the differential and niche responses of the three ammonia oxidising communities to N substrate additions and nitrification inhibitor treatments. Further research is needed to investigate the specificity of the two inhibitors on the different ammonia oxidising communities.

BackgroundReasonable and effective time allocation can promote the improvement of medical care service quality. This study aimed to translate, cross-culturally adapt and validate the Chinese Nursing Time Management Scale (NTMS).MethodsUsing a cross-sectional survey, 345 clinical nurses were selected from June to September 2023 for a general information questionnaire and Nursing Time Management Scale (NTMS) study. Item analysis, exploratory factor analysis and validation factor analysis were used to verify the reliability and validity of the Chinese version of Nursing Time Management Scale.ResultsThe Chinese version of the Nurses’ Time Management Competency Scale includes 17 entries in 3 dimensions: planning activities and setting goals, coordinating activities and procedures, and organizing nursing activities. The Cronbach’s alpha coefficient for the total scale was 0.966. Exploratory factor analysis showed that the cumulative variance contribution of the three male factors was 97.44%.ConclusionThe NTMS has acceptable validity and reliability and can be used to evaluate the nursing time management skills of Chinese clinical nurses.

Abstract The COVID-19 outbreak has had a significant impact on higher education worldwide. In-person courses had to be quickly transited to online, including lab courses embedded with Course-based Undergraduate Research Experiences (CUREs). In response to this challenge, we successfully converted a fully in-person biochemistry lab that integrated with a 6-week modular CURE (mCURE) into a hybrid CURE (hCURE) in Fall 2020, with support from the Malate dehydrogenase CUREs Community. The hCURE was structured to have in-person labs and online activities arranged on an alternating weekly basis, so that only half of the regular class size of students attended the hands-on labs at any given time to maintain proper social distancing. To evaluate the efficacy of the hCURE, student science self-efficacy and conceptual understanding of protein structure–function relationships were measured using pre-course and post-course surveys and tests, respectively. Our data showed a significant increase in student science self-efficacy and conceptual knowledge test scores. Furthermore, we compared the pre-lab quiz scores that assessed various biochemical concepts and skills across three different semesters, Fall 2019 with a fully in-person mCURE before the pandemic, Fall 2020 with the hCURE implemented during the pandemic, and Fall 2021 when the lab returned to the fully in-person mCURE following the pandemic. A significant decline in quiz scores from Fall 2019 to Fall 2020, and an even further decline from Fall 2019 to Fall 2021 were observed, suggesting that apart from the impact of course modality, the pandemic may have exerted a lasting adverse effect on student learning.

Alpine forest soil in the southeastern Qinghai–Xizang Plateau plays a crucial role in regional and global climate and biogeochemical cycles, yet the elevational distribution of soil nitrogen (N) availability and losing risk is unresolved. In this study, we characterized soil N composition and key N transformation processes across different elevations in 3 typical mounts of the Qinghai–Xizang Plateau. In contrast to previous suggestions, soil total N and ammonium are found to accumulate in high elevation zones. This accumulation of N at higher altitudes is due to a consistent soil net N mineralization rate coupled with an extremely low net nitrification rate, which is suppressed by low pH and high soil moisture in high elevation zones. Moreover, the elevated rates of biological N fixation along the elevation further contribute to N accumulation in high elevation regions in which the acid-tolerant Bradyrhizobium, plant-associated Herbaspirillum, and Klebsiella are identified as the key diazotrophic microbial taxa responsible for active N fixation. Collectively, our results suggest that total N and NH4+-N accumulation in higher altitude zone is a ubiquitous phenomenon in the southeast Qinghai–Xizang Plateau, with lower nitrification rates and higher biological nitrogen fixation being key processes enabling this occurrence.

Objective: To establish a quantitative analysis of multi-components by single marker (QAMS) method for the determination of lovastatin and lovastatin acid for the quality control of Hongqu Fuling tablets. Methods: Lovastatin as a control, the RP-HPLC method was used to establish the relationship between the correction factor of lovastatin and lovastatin acid, and to simultaneously quantify both lovastatin and lovastatin acid in the Hongqu Fuling tablets by QAMS. Results: The negative sample had no interference, the specificity of the sample detection method was good, the linear relationship between lovastatin and lovastatin acid was good within the corresponding linear range, R2>0.9999, the precision and repeatability RSD values were less than 3%, and the recovery was 98.43%～103.18%. The relative correction factor of lovastatin acid and lovastatin was 0.9000, and the repeatability was good. The average content of lovastatin acid was 0.3563 mg/g determined by QAMS, and the average content of lovastatin acid determined by external standard method was 0.3668 mg/g, and the average content of lovastatin was 1.1113 mg/g, which indicated that the constructed QAMS method could be used for the multi-component quality evaluation research of Hongqu Fuling Tablets. Conclusion: The QAMS method established in this study was stable, accurate and specific, and would provide a scientific basis for the quality control and in-depth development of Hongqu Fuling tablets.

The arginine vasopressin (AVP)-magnocellular neurosecretory system (AVPMNS) in the hypothalamus plays a critical role in homeostatic regulation as well as in allostatic motivational behaviors. However, it remains unclear whether adult neurogenesis exists in the AVPMNS. By using immunoreaction against AVP, neurophysin II, glial fibrillar acidic protein (GFAP), cell division marker (Ki67), migrating neuroblast markers (doublecortin, DCX), microglial marker (Ionized calcium binding adaptor molecule 1, Iba1), and 5′-bromo-2′-deoxyuridine (BrdU), we report morphological evidence that low-rate neurogenesis and migration occur in adult AVPMNS in the rat hypothalamus. Tangential AVP/GFAP migration routes and AVP/DCX neuronal chains as well as ascending AVP axonal scaffolds were observed. Chronic water deprivation significantly increased the BrdU+ nuclei within both the supraaoptic (SON) and paraventricular (PVN) nuclei. These findings raise new questions about AVPMNS’s potential hormonal role for brain physiological adaptation across the lifespan, with possible involvement in coping with homeostatic adversities.

Currently, an increasing number of macaque brain MRI datasets are being made publicly accessible. Unlike human, publicly accessible macaque brain datasets suffer from data quality in diffusion magnetic resonance imaging (dMRI) data. Typically, dMRI data require a minimum ratio of 1:10 between low b-value (b < 10) volumes and high b-value (b > 300) volumes. However, the currently accessible macaque datasets do not meet this ratio. Due to site differences in macaque brain images, traditional human brain image-to-image translation models struggle to perform well on macaque brain images. Our work introduces a novel end-to-end primary-auxiliary dual generative adversarial network (PadGAN) for generating low b-value images. The auxiliary generator in the PadGAN is responsible for extracting the latent space features from peak information maps and transmitting them to the primary generator, enabling the primary generator to generate images with rich details. Experimental results demonstrate that PadGAN outperforms existing methods both qualitatively and quantitatively (mean SSIM increased by 0.1139). Diffusion probabilistic tractography using dMRI data augmented by our method yields superior results.

Abstract In order to improve the accuracy of the parameters needed in the discrete element method (DEM) simulation process of wet-sticky feed raw materials, the JKR contact model in DEM was used to calibrate and verify the physical parameters of wet-sticky feed raw materials. Firstly, the parameters that have a significant effect on the angle of repose were screened using a Plackett–Burman design, and the screened parameters were: MM rolling friction coefficient, MM static friction coefficient, and JKR surface energy. Then, the three screened parameters were selected as the influencing factors and the accumulation angle of repose was selected as evaluating indicator; thus, the performance optimization experiments were carried out with the quadratic orthogonal rotation design. Taking the experimentally measured angle of repose value of 54.25°as the target value, the significance parameters were optimized, and the optimal combination was obtained : MM rolling friction factor was 0.21, MM static friction factor was 0.51, and JKR surface energy was 0.65. Finally, the angle of repose and SPP tests were compared under the calibrated parameters. The results showed that the relative error of experimental and simulated tests in angle of repose was 0.57%, and the compression displacement and compression ratio of the experimental and simulated tests in SPP were 1.01% and 0.95%, respectively, which improved the reliability of the simulated results. The research findings provide a reference basis for simulation study and optimal design of related equipment for feed raw materials.

Abstract It is important to explore the effective approaches to prevent dry age-related macular degeneration (AMD). In this study, significantly decreased full-field electroretinograms wave amplitudes and disordered retina structures were detected in rat retinas of sodium iodate induced dry AMD model. Six a- and b-wave amplitudes and the antioxidant activities were significantly increased, and the outer nuclear layer thickness was significantly improved in the rat retinas treated with the combination of Lactobacillus fermentum NS9 (LF) and aronia anthocyanidin extract (AAE) compared with the model. The effects were much better than the treatment with AAE alone. The proteomics analysis showed the expressions of α-, β- and γ-crystallins were increased by 3–8 folds in AAE treated alone and by 6–11 folds in AAE + LF treatment compared with the model, which was further confirmed by immuno-blotting analysis. Analysis of gut microbial composition indicated that higher abundance of the genus Parasutterella and species P. excrementihominis was found in the AAE + LF treatment compared with the other groups. The results indicated that the combined treatment of AAE + LF is a potential way to prevent the retina degeneration which is significantly better than the AAE treated alone.

PurposeTo investigate the effects of postoperative astigmatism on the visual outcomes following presbyopia-correcting surgery with multifocal intraocular lens implantation.MethodsA comprehensive literature search was conducted using PubMed, Embase, and Web of Science for articles published until January 2023. Additionally, we included retrospective case series and prospective comparative studies. The combined mean difference (MD) with 95% confidence intervals (CI) and odds ratio (OR) with 95% CI were used to express continuous and categorical outcomes, respectively. All statistical analyses were performed using Review Manager (version 5.4.1).ResultsWe included nine eligible studies that analyzed 3,088 eyes. The proportion of eyes with useful postoperative visual acuity (logMAR ≤ 0.20) and residual astigmatism significantly differed with respect to the magnitude of astigmatism and presence/absence of blurred vision (p

The toxic heavy metal cadmium (Cd) has a significant impact on kidney health. Documents manifested that non-toxic flavonoid quercetin can reduce Cd-induced kidney damage by reducing oxidative stress and inhibiting apoptosis, while the effect of quercetin on Cd-induced renal cell pyroptosis has not been elucidated. In this study, we established a model of Cd poisoning treated with quercetin both in vitro and in vivo. Results revealed that quercetin effectively reversed the decrease in Cd-induced cell viability. Furthermore, Cd increased blood urea nitrogen while reducing GPX and SOD levels, caused histopathological injuries in kidney with a significantly elevated cell pyroptosis characterized by enhanced levels of proteins representing assembly (NLRP3) and activation (pro IL-1β, cleaved IL-1β, and IL-18) of NLRP3 inflammasome as well as pyroptosis executor (pro caspase-1, cleaved caspase-1). However, quercetin administration alleviated kidney injuries above by decreasing cell pyroptosis. Overall, it suggests that kidney cells are susceptible to pyroptotic cell death due to Cd exposure; while quercetin exhibits protective effects through cell pyroptosis inhibition.

Abstract Background Stomach hemorrhage and perforation are very severe and common complications in patients with primary gastric diffuse large B‐cell lymphoma (PG‐DLBCL) during treatment with immunochemotherapy. However, no relevant clinical studies have been performed on the prevention of these serious complications. Methods Patients diagnosed with PG‐DLBCL were enrolled in this retrospective study. The prevention group received standard rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R‐CHOP) treatment without prednisone combined with antacids and anti‐Helicobacter pylori (Hp) therapy. These patients received R‐CHOP‐based treatment until the complete recovery of gastric ulcers, as proven by gastroscopy. The control group received a standard R‐CHOP regimen. Toxicity and survival were the main endpoints. Results A total of 52 patients received preventative treatment, while 146 patients did not. Among patients with stage I, II‐1, and II‐2 disease, the prevention group had a lower rate of hemorrhage and perforation (0/40) than the control group (10/78, p = 0.044). At a median follow‐up time of 25 months, the 5‐year event‐free survival (EFS) rates were 97.1% in the prevention group and 66.1% in the control group (p = 0.025), and the 5‐year overall survival (OS) rates were 100% and 72.0%, respectively (p = 0.021). However, the differences in the 5‐year EFS and OS of patients with disseminated disease were not statistically significant. Conclusions Preventative treatment can decrease the risk of hemorrhage and perforation in patients with localized PG‐DLBCL during immunochemotherapy, leading to better EFS and OS in these patients. However, preventative treatment failed to reduce the risk of gastric hemorrhage and perforation and did not improve survival (EFS and OS) in advanced‐stage patients.

Platelets play a vital role in cancer and immunity. However, few comprehensive studies have been conducted on the role of platelet-related signaling pathways in various cancers and their responses to immune checkpoint blockade (ICB) therapy. In the present study, we focused on the glycoprotein VI-mediated platelet activation (GMPA) signaling pathway and comprehensively evaluated its roles in 19 types of cancers listed in The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Cox regression and meta-analyses showed that for all 19 types of cancers, patients with high GMPA scores tended to have a good prognosis. Furthermore, the GMPA signature score could serve as an independent prognostic factor for patients with skin cutaneous melanoma (SKCM). The GMPA signature was linked to tumor immunity in all 19 types of cancers, and was correlated with SKCM tumor histology. Compared to other signature scores, the GMPA signature scores for on-treatment samples were more robust predictors of the response to anti-PD-1 blockade in metastatic melanoma. Moreover, the GMPA signature scores were significantly negatively correlated with EMMPRIN (CD147) and positively correlated with CD40LG expression at the transcriptomic level in most cancer patient samples from the TCGA cohort and on-treatment samples from anti-PD1 therapy cohorts. The results of this study provide an important theoretical basis for the use of GMPA signatures, as well as GPVI-EMMPRIN and GPVI-CD40LG pathways, to predict the responses of cancer patients to various types of ICB therapy.

There are many bars in grid structures, and their topological relationships are complex, so the workload of calculations involved in researching their reliability is large. In this paper, based on the geometric topological relationship within a grid structure, a series–parallel system analysis of the structure is carried out by means of node analysis, constraint grade division, and hierarchical combination analysis, and the series–parallel analysis results for the structure are used to judge the failure of the structure. In order to avoid the problem of missing important components due to unreasonable selection of the bounding threshold when identifying failed components, an adaptive dynamic bounding threshold method with high accuracy is introduced. The failure probability value of the failure path is calculated using the direct numerical integration method, and the reliability of the whole structure is obtained. Finally, the validity of this method is verified using an example of a square pyramid grid structure. The results show that the method is feasible for series–parallel system analysis, structural failure judgment, and reliability analysis of a grid structure.

Hydropericardium hepatitis syndrome (HHS) is primarily caused by fowl adenovirus serotype 4 (FAdV-4), causing high mortality in chickens. Although vaccination strategies against FAdV-4 have been adopted, HHS still occurs sporadically. Furthermore, no effective drugs are available for controlling FAdV-4 infection. However, type I and III interferon (IFN) are crucial therapeutic agents against viral infection. The following experiments were conducted to investigate the inhibitory effect of chicken IFN against FadV-4. We expressed recombinant chicken type I IFN-α (ChIFN-α) and type III IFN-λ (ChIFN-λ) in Escherichia coli and systemically investigated their antiviral activity against FAdV-4 infection in Leghorn male hepatocellular (LMH) cells. ChIFN-α and ChIFN-λ dose dependently inhibited FAdV-4 replication in LMH cells. Compared with ChIFN-λ, ChIFN-α more significantly inhibited viral genome transcription but less significantly suppressed FAdV-4 release. ChIFN-α- and ChIFN-λ-induced IFN-stimulated gene (ISG) expression, such as PKR, ZAP, IRF7, MX1, Viperin, IFIT5, OASL, and IFI6, in LMH cells; however, ChIFN-α induced a stronger expression level than ChIFN-λ. Thus, our data revealed that ChIFN-α and ChIFN-λ might trigger different ISG expression levels, inhibiting FAdV-4 replication via different steps of the FAdV-4 lifecycle, which furthers the potential applications of IFN antiviral drugs in chickens.

Background: The tumor-associated endothelial cell (TAE) component plays a vital role in tumor immunity. However, systematic tumor-associated endothelial-related gene assessment models for predicting cancer immunotherapy (CIT) responses and survival across human cancers have not been explored. Herein, we investigated a TAE gene risk model to predict CIT responses and patient survival in a pan-cancer analysis.Methods: We analyzed publicly available datasets of tumor samples with gene expression and clinical information, including gastric cancer, metastatic urothelial cancer, metastatic melanoma, non-small cell lung cancer, primary bladder cancer, and renal cell carcinoma. We further established a binary classification model to predict CIT responses using the least absolute shrinkage and selection operator (LASSO) computational algorithm.Results: The model demonstrated a high predictive accuracy in both training and validation cohorts. The response rate of the high score group to immunotherapy in the training cohort was significantly higher than that of the low score group, with CIT response rates of 51% and 27%, respectively. The survival analysis showed that the prognosis of the high score group was significantly better than that of the low score group (all p < 0·001). Tumor-associated endothelial gene signature scores positively correlated with immune checkpoint genes, suggesting that immune checkpoint inhibitors may benefit patients in the high score group. The analysis of TAE scores across 33 human cancers revealed that the TAE model could reflect immune cell infiltration and predict the survival of cancer patients.Conclusion: The TAE signature model could represent a CIT response prediction model with a prognostic value in multiple cancer types.

IntroductionAstigmatism reduces the postoperative visual performance after non-toric intraocular lenses (IOLs) implantation, and limits the use of refractive IOLs in cataract surgery. The purpose of this study was to compare the efficacy in astigmatism correction and the postoperative visual outcomes between the implantation of a trifocal IOL with femtosecond laser-assisted arcuate keratotomy (FSAK) in one eye and a bifocal toric IOL (TIOL) in the other, in patients with cataract and moderate astigmatism.MethodsThis prospective observational paired-eye study enrolled patients with cataract and corneal astigmatism (CA) between 0.75 and 2.25 D in both eyes. The patients underwent a mix-and-match treatment comprising trifocal IOL implantation with FSAK and bifocal TIOL implantation. We compared the visual acuity (VA) at all distances, defocus curve, postoperative refractive astigmatism (RfA), CA, high-order aberrations, modulation transfer function (MTF) curve, and Strehl ratio between the two eye groups.ResultsIn total, 41 patients (82 eyes) were enrolled and completed a 6-month follow-up. The 1- and 3-month uncorrected distance VA and 3-month uncorrected near VA were greater in eyes with bifocal TIOLs than with trifocal IOLs and FSAK (p = 0.036, 0.010, and 0.030, respectively), whereas the latter had greater uncorrected intermediate VA at every visit and greater VA in the intermediate range of defocus curve (at −1.50 and − 2.00 D) than the eyes with bifocal TIOLs. The postoperative RA of the eyes with trifocal IOL and FSAK was significantly higher than that of the bifocal TIOL-implanted eyes at the 3- and 6-month follow-ups.DiscussionBoth FSAK and TIOL implantation effectively reduce pre-existing moderate astigmatism in patients with cataract. The eyes with bifocal TIOLs had more stable long-term astigmatism correction, whereas those with trifocal IOLs and FSAK had better intermediate VA. Therefore, a mix-and-match implantation of trifocal IOL with FSAK and contralateral bifocal TIOL could achieve effective astigmatism correction and provide an overall optimal VA.

PurposeThe aim of this study was to evaluate the effect of residual astigmatism on postoperative visual outcomes after trifocal intraocular lens implantation.MethodsIn this prospective observational study, we divided 156 eyes into two groups according to postoperative astigmatism measured by subjective optometry and followed them up for 3 months. Visual acuity, modulation transfer function (MTF) curves, Strehl ratio (SR), Visual Function Index-14 scores, and photic phenomena were compared.ResultsLinear regression analysis revealed a weak correlation between residual astigmatism and uncorrected distance visual acuity (UDVA) (r = 0.190, P = 0.016) at 3 months and a significant between-group difference at 1- and 3-month postoperative UDVA (P = 0.038, P = 0.018, respectively). MTF curve values and SR (MTF-10 total, MTF-10 cornea, MTF-30 total, MTF-30 cornea, SR Total, and SR cornea) were significantly worse (P < 0.001), and the Visual Function Index-14 scores were lower in the 0.5 < astigmatism ≤ 1.25 D group (P < 0.05) than in the astigmatism ≤ 0.5 D group. No significant differences were found in the frequency, severity, and bothersomeness of photic phenomena (P > 0.05).ConclusionPostoperative residual astigmatism affects the UDVA of the trifocal intraocular lens-implanted eyes. Although we found no significant differences in uncorrected intermediate and near visual acuity, both objective and subjective visual quality were affected, suggesting the need for surgical planning when the anticipated postoperative astigmatism is >0.5 D.

Abstract Background Activated microglia play a key role in initiating the inflammatory cascade following ischemic stroke and exert proinflammatory or anti-inflammatory effects, depending on whether they are polarized toward the M1 or M2 phenotype. The present study investigated the regulatory effect of icaritin (ICT) on microglial polarization in rats after cerebral ischemia/reperfusion injury (CI/RI) and explored the possible anti-inflammatory mechanisms of ICT. Methods A rat model of transient middle cerebral artery occlusion (tMCAO) was established. Following treatment with ICT, a G protein-coupled estrogen receptor (GPER) inhibitor or an extracellular signal-regulated kinase (ERK) inhibitor, the Garcia scale and rotarod test were used to assess neurological and locomotor function. 2,3,5-Triphenyltetrazolium chloride (TTC) and Fluoro-Jade C (FJC) staining were used to evaluate the infarct volume and neuronal death. The levels of inflammatory factors in the ischemic penumbra were evaluated using enzyme-linked immunosorbent assays (ELISAs). In addition, western blotting, immunofluorescence staining and quantitative PCR (qPCR) were performed to measure the expression levels of markers of different microglial phenotypes and proteins related to the GPER–ERK–nuclear factor kappa B (NF-κB) signaling pathway. Results ICT treatment significantly decreased the cerebral infarct volume, brain water content and fluorescence intensity of FJC; improved the Garcia score; increased the latency to fall and rotation speed in the rotarod test; decreased the levels of interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), Iba1, CD40, CD68 and p-P65-NF-κB; and increased the levels of CD206 and p-ERK. U0126 (an inhibitor of ERK) and G15 (a selective antagonist of GPER) antagonized these effects. Conclusions These findings indicate that ICT plays roles in inhibiting the inflammatory response and achieving neuroprotection by regulating GPER–ERK–NF-κB signaling and then inhibiting microglial activation and M1 polarization while promoting M2 polarization, which provides a new therapeutic for against cerebral ischemic stroke. Graphical Abstract

Practical applications of perception, communication, computing, etc. in modern energy industry continually generate large scale data from diversified monitoring terminals. Such massive information has the characteristics like heterogeneity, time sequence, low value density, etc. To promptly obtain high quality data served for safe operation of power network, this paper developed a simultaneous prediction algorithm for multiple source–loads combing sliding time window with convolutional neural network (CNN). The contributions lie in such aspects as extraction of high-value training samples, construction of CNN catered for multiple source–loads and prediction efficiency. Firstly, after the incomplete and abnormal information of raw samples are processed through median filtering and interpolation, the correlation analysis of time series and sliding time window are employed to extract high-value training samples served for CNN. Also, a simultaneous prediction model suitable for multiple source–loads is constructed by modifying CNN. In addition, integrated with the characteristics of the proposed CNN architecture, the parallel strategies based on task parallel and data parallel are designed to achieve rapidly quality prediction for massive and heterogeneous energy sources and loads. Extensive experimental results demonstrate that the proposed algorithm can obtain the higher predicting accuracy simultaneously satisfying requirements of diversified energy source and loads. Loads of experimental comparisons in multicore chips show that the proposed parallel strategies can offer increased speedup under massive prediction.

Abstract Exercise training (ExT) is capable of improving the heart function of spontaneously hypertensive rats (SHRs), but the underlying molecular mechanisms remain elusive. This study was aimed to investigate whether inhibition of RhoA/ROCK signaling pathway contributes to the cardiac protection by low-intensity ExT in SHRs. The results demonstrated that, compared with Wistar-Kyoto (WKY) rats, SHRs obviously exhibited higher blood pressure, increased heart weight index and thickness of left ventricular wall, decreased left ventricular function, damaged myocardial construction, and increased collagen fiber of left ventricle (P

There are increasing epilepsy patients suffering from the pain of seizure onsets, and effective prediction of seizures could improve their quality of life. To obtain high sensitivity for epileptic seizure prediction, current studies generally need complex feature extraction operations, which heavily depends on the artificial experience (or domain knowledge) and is highly subjective. To address these issues, in this paper we propose an end-to-end epileptic seizure prediction approach based on the long short-term memory network (LSTM). In the new method, only the gamma band of raw electroencephalography (EEG) signals is extracted as network input directly for seizure prediction, thus avoiding subjective and expensive feature design process. Despite its simplicity, the proposed method achieves the mean sensitivity of 91.76% and false prediction rate (FPR) of 0.29/h on Children’s Hospital Boston-MIT (CHB-MIT) scalp EEG Database, respectively, when identifying the preictal stage from the EEG signals. Furthermore, different from traditional methods that only consider the classification of preictal and interictal EEG, we introduce the postictal stage as an extra class in the proposed method. As a result, the performance of seizure prediction is further improved, obtaining a higher sensitivity of 92.17% and a low FPR of 0.27/h. The mean warning time is 44.46 min, which suggests that sufficient time is reserved for patients to take intervention measures by this prediction method.

BACKGROUND: Recent studies have reported higher risks of adverse maternal and neonatal outcomes, such as hypertensive disorders of pregnancy, after programmed frozen embryo transfer, especially in cycles with gonadotropin-releasing hormone agonist pretreatment. It remains unclear if GnRH agonist pretreatment before programmed frozen embryo transfer further increases the risk for obstetrical complications among women with polycystic ovary syndrome. OBJECTIVE: This study aimed to compare the obstetrical and neonatal complications of singleton and twin pregnancies after programmed frozen embryo transfer with or without gonadotropin-releasing hormone-a pretreatment among women with polycystic ovary syndrome. STUDY DESIGN: This was a secondary analysis of a single-center, randomized controlled trial comparing the live birth rate and cost-effectiveness of programmed cycle-prepared frozen embryo transfers with or without gonadotropin-releasing hormone agonist pretreatment among women with polycystic ovary syndrome. The analysis was restricted to women with polycystic ovary syndrome, aged 24 to 40 years, who delivered live neonates after frozen-thawed blastocyst transfer. The obstetrical and neonatal outcomes were compared between programmed cycles with and those without gonadotropin-releasing hormone agonist pretreatment. The adjusted odds ratios with 95% confidence intervals were calculated and adjustments were made for relevant confounders. RESULTS: The maternal and neonatal complications associated with 177 live single births and 38 twin births (253 newborns in total) were analyzed. There were no significant differences in the frequencies of obstetrical complications, including hypertensive disorders of pregnancy, between the gonadotropin-releasing hormone agonist pretreatment and no pretreatment group for both singleton and twin pregnancies. However, there was a significantly greater incidence of having a low birthweight neonate among singleton infants born after gonadotropin-releasing hormone agonist pretreatment when compared with no pretreatment (10.2% vs 1.3%; P=0.042), and a low birthweight among singleton infants was still more likely after adjusting for confounders (relative ratio, 3.85; 95% confidence interval, 1.13−7.11; P=.024). Other neonatal complications were all comparable between the pretreatment and no pretreatment groups for both singleton and twin pregnancies. CONCLUSION: For women with polycystic ovary syndrome, programmed frozen embryo transfer cycles with gonadotropin-releasing hormone agonist pretreatment could lead to a greater risk of having a low birthweight singleton neonate.

Learning activities based on translation has attracted increasing attention among researchers in English as a Foreign Language (EFL) teaching and learning under the influence of translanguaing pedagogies. This study was designed to examine the effect of translation methods as pedagogical tools on students’ writing performance in EFL classrooms. 89 Chinese college students participated in the study. They were required to complete tests of essay writing before and after the use of the translation method. Nine students were invited to attend an interview after the writing test. Results showed that the students improved their essay writing performance significantly after the translation method. The participating students’ confidence and interest in essay writing were also enhanced. Findings from the study have important implications for effective writing instruction for Chinese EFL college students.

The mitochondrial unfolded protein response (UPRmt) is a stress response pathway that regulates the expression of mitochondrial chaperones, proteases, and other proteins involved in protein folding and degradation, thereby ensuring proper mitochondrial function. In addition to this critical function, the UPRmt also plays a role in other cellular processes such as mitochondrial biogenesis, energy metabolism, and cellular signaling. Moreover, the UPRmt is strongly associated with various diseases. From 2004 to 2022, there has been a lot of interest in UPRmt. The present study aims to utilized bibliometric tools to assess the genesis, current areas of focus, and research trends pertaining to UPRmt, thereby highlighting avenues for future research. There were 442 papers discovered to be related to UPRmt, with the overall number of publications rising yearly. International Journal of Molecular Sciences was the most prominent journal in this field. 2421 authors from 1,402 institutions in 184 nations published studies on UPRmt. The United States was the most productive country (197 documents). The top three authors were Johan Auwerx, Cole M Haynes, and Dongryeol Ryu. The early focus of UPRmt is “protein.” And then the UPRmt research shifted from Caenorhabditis elegans back to mammals, and its close link to aging and various diseases. The top emerging research hotspots are neurodegenerative diseases and metabolic diseases. These findings provide the trends and frontiers in the field of UPRmt, and valuable information for clinicians and scientists to identify new perspectives with potential collaborators and cooperative countries.

Brain functional network (BFN) analysis has become a popular technique for identifying neurological/mental diseases. Due to the fact that BFN is a graph, a graph convolutional network (GCN) can be naturally used in the classification of BFN. Different from traditional methods that directly use the adjacency matrices of BFNs to train a classifier, GCN requires an additional input-node features. To our best knowledge, however, there is no systematic study to analyze their influence on the performance of GCN-based brain disorder classification. Therefore, in this study, we conduct an empirical study on various node feature measures, including (1) original fMRI signals, (2) one-hot encoding, (3) node statistics, (4) node correlation, and (5) their combination. Experimental results on two benchmark databases show that different node feature inputs to GCN significantly affect the brain disease classification performance, and node correlation usually contributes higher accuracy compared to original signals and manually extracted statistical features.

IntroductionFunctional brain networks (FBNs) estimated from functional magnetic resonance imaging (fMRI) data has become a potentially useful way for computer-aided diagnosis of neurological disorders, such as mild cognitive impairment (MCI), a prodromal stage of Alzheimer's Disease (AD). Currently, Pearson's correlation (PC) is the most widely-used method for constructing FBNs. Despite its popularity and simplicity, the conventional PC-based method usually results in dense networks where regions-of-interest (ROIs) are densely connected. This is not accordance with the biological prior that ROIs may be sparsely connected in the brain. To address this issue, previous studies proposed to employ a threshold or l_1-regularizer to construct sparse FBNs. However, these methods usually ignore rich topology structures, such as modularity that has been proven to be an important property for improving the information processing ability of the brain.MethodsTo this end, in this paper, we propose an accurate module induced PC (AM-PC) model to estimate FBNs with a clear modular structure, by including sparse and low-rank constraints on the Laplacian matrix of the network. Based on the property that zero eigenvalues of graph Laplacian matrix indicate the connected components, the proposed method can reduce the rank of the Laplacian matrix to a pre-defined number and obtain FBNs with an accurate number of modules.ResultsTo validate the effectiveness of the proposed method, we use the estimated FBNs to classify subjects with MCI from healthy controls. Experimental results on 143 subjects from Alzheimer's Disease Neuroimaging Initiative (ADNI) with resting-state functional MRIs show that the proposed method achieves better classification performance than previous methods.

Perfluoroalkyl acids (PFAAs) are contaminants of global concern, and the inadvertent consumption of PFAA-contaminated crops may pose a threat to public health. Therefore, systematically studying their source tracing, bioaccumulation prediction and risk assessments in crops is an urgent priority. This study investigated the source apportionment and transport of PFAAs and novel fluorinated alternatives (collectively as per- and polyfluoroalkyl substances, PFASs) from factories to agricultural fields in a fluorochemical industrial region of China. Furthermore, bioaccumulation specificities and prediction of these chemicals in different vegetables were explored, followed by a comprehensive risk assessment from agricultural fields to dinner plates which considered precursor degradation. A positive matrix factorization model revealed that approximately 70 % of PFASs in agricultural soils were derived from fluorochemical manufacturing and metal processing. Alarming levels of ∑PFASs ranged 8.28–84.3 ng/g in soils and 163–7176 ng/g in vegetables. PFAS with short carbon chain or carboxylic acid group as well as branched isomers exhibited higher environmental transport potentials and bioaccumulation factors (BAFs) across a range of vegetables. The BAFs of different isomers of perfluorooctanoic acid (PFOA) decreased as the perfluoromethyl group moved further from the acid functional group. Hexafluoropropylene oxide dimer acid (GenX) showed relatively low BAFs, probably related to its ether bond with a high affinity to soil. Vegetables with fewer Casparian strips (e.g., carrot and radish), or more protein, possessed larger BAFs of PFASs. A bioaccumulation equation integrating critical parameters of PFASs, vegetables and soils, was built and corroborated with a good contamination prediction. After a total oxidizable precursors (TOP) assay, incremental perfluoroalkyl carboxylic acids (PFCAs) were massively found (325–5940 ng/g) in edible vegetable parts. Besides, precursor degradation and volatilization loss of PFASs was firstly confirmed during vegetable cooking. A risk assessment based on the TOP assay was developed to assist the protection of vegetable consumers.

Secondary spinal cord injury (SSCI) is the second stage of spinal cord injury (SCI) and involves vasculature derangement, immune response, inflammatory response, and glial scar formation. Bioactive additives, such as drugs and cells, have been widely used to inhibit the progression of secondary spinal cord injury. However, the delivery and long-term retention of these additives remain a problem to be solved. In recent years, hydrogels have attracted much attention as a popular delivery system for loading cells and drugs for secondary spinal cord injury therapy. After implantation into the site of spinal cord injury, hydrogels can deliver bioactive additives in situ and induce the unidirectional growth of nerve cells as scaffolds. In addition, physical and chemical methods can endow hydrogels with new functions. In this review, we summarize the current state of various hydrogel delivery systems for secondary spinal cord injury treatment. Moreover, functional modifications of these hydrogels for better therapeutic effects are also discussed to provide a comprehensive insight into the application of hydrogels in the treatment of secondary spinal cord injury.

Background: Pancreatic cancer is a malignancy with a high mortality rate and worse prognosis. Recently, public databases and bioinformatics tools make it easy to develop the prognostic risk model of pancreatic cancer, but the aging-related risk signature has not been reported. The present study aimed to identify an aging-related risk signature with potential prognostic value for pancreatic cancer patients.Method: Gene expression profiling and human clinical information of pancreatic cancer were derived from The Cancer Genome Atlas database (TCGA). Aging-related gene sets were downloaded from The Molecular Signatures Database and aging-related genes were obtained from the Human Ageing Genomic Resources database. Firstly, Gene set enrichment analysis was carried out to investigate the role of aging process in pancreatic cancer. Secondly, differentially expressed genes and aging-related prognostic genes were screened on the basis of the overall survival information. Then, univariate COX and LASSO analysis were performed to establish an aging-related risk signature of pancreatic cancer patients. To facilitate clinical application, a nomogram was established to predict the survival rates of PCa patients. The correlations of risk score with clinical features and immune status were evaluated. Finally, potential therapeutic drugs were screened based on the connectivity map (Cmap) database and verified by molecular docking. For further validation, the protein levels of aging-related genes in normal and tumor tissues were detected in the Human Protein Atlas (HPA) database.Result: The genes of pancreatic cancer were markedly enriched in several aging-associated signaling pathways. We identified 14 key aging-related genes related to prognosis from 9,020 differentially expressed genes and establish an aging-related risk signature. This risk model indicated a strong prognostic capability both in the training set of TCGA cohort and the validation set of PACA-CA cohort and GSE62452 cohort. A nomogram combining risk score and clinical variables was built, and calibration curve and Decision curve analysis (DCA) have proved that it has a good predictive value. Additionally, the risk score was tightly linked with tumor immune microenvironment, immune checkpoints and proinflammatory factors. Moreover, a candidate drug, BRD-A47144777, was screened and verified by molecular docking, indicating this drug has the potential to treat PCa. The protein expression levels of GSK3B, SERPINE1, TOP2A, FEN1 and HIC1 were consistent with our predicted results.Conclusion: In conclusion, we identified an aging-related signature and nomogram with high prediction performance of survival and immune cell infiltration for pancreatic cancer. This signature might potentially help in providing personalized immunotherapy for patients with pancreatic cancer.

Tree peonies are an economically important crop with flowers of high ornamental value. Most tree peony cultivars in gardens are once-flowering, and the continuous flowering (CF) trait has been revealed only in a few tree peony cultivars, such as ‘High Noon’ (‘HN’). However, the molecular mechanism underlying its CF remains unclear. Here, we demonstrated that PsTFL1 functions as a floral inhibitor via the ectopic expression of PsTFL1 in transgenic Arabidopsis thaliana plants. Our findings suggest that PsFT and PsTFL1 interact with PsFD, and the detected interactions may occur in the nucleus. Compared with the non-CF variety, the gene expression patterns of PsFT, PsTFL1, and PsFD during the flower development indicate that these three genes may be related to the CF habit in tree peony ‘HN’. These findings will aid future investigations of CF behavior and promote the breeding of tree peonies and other perennial woody plants.

Functional connectivity network (FCN) has become a popular tool to identify potential biomarkers for brain dysfunction, such as autism spectrum disorder (ASD). Due to its importance, researchers have proposed many methods to estimate FCNs from resting-state functional MRI (rs-fMRI) data. However, the existing FCN estimation methods usually only capture a single relationship between brain regions of interest (ROIs), e.g., linear correlation, nonlinear correlation, or higher-order correlation, thus failing to model the complex interaction among ROIs in the brain. Additionally, such traditional methods estimate FCNs in an unsupervised way, and the estimation process is independent of the downstream tasks, which makes it difficult to guarantee the optimal performance for ASD identification. To address these issues, in this paper, we propose a multi-FCN fusion framework for rs-fMRI-based ASD classification. Specifically, for each subject, we first estimate multiple FCNs using different methods to encode rich interactions among ROIs from different perspectives. Then, we use the label information (ASD vs. healthy control (HC)) to learn a set of fusion weights for measuring the importance/discrimination of those estimated FCNs. Finally, we apply the adaptively weighted fused FCN on the ABIDE dataset to identify subjects with ASD from HCs. The proposed FCN fusion framework is straightforward to implement and can significantly improve diagnostic accuracy compared to traditional and state-of-the-art methods.

The recent discovery of comammox Nitrospira, a complete ammonia oxidizer, capable of completing the nitrification on their own has presented tremendous challenges to our understanding of the nitrification process. There are two divergent clades of comammox Nitrospira, Clade A and B. However, their population abundance, community structure and role in ammonia and nitrite oxidation are poorly understood. We conducted a 94-day microcosm study using a grazed dairy pasture soil amended with urea fertilizers, synthetic cow urine, and the nitrification inhibitor, dicyandiamide (DCD), to investigate the growth and community structure of comammox Nitrospira spp. We discovered that comammox Nitrospira Clade B was two orders of magnitude more abundant than Clade A in this fertile dairy pasture soil and the most abundant subcluster was a distinctive phylogenetic uncultured subcluster Clade B2. We found that comammox Nitrospira Clade B might not play a major role in nitrite oxidation compared to the role of canonical Nitrospira nitrite-oxidizers, however, comammox Nitrospira Clade B is active in nitrification and the growth of comammox Nitrospira Clade B was inhibited by a high ammonium concentration (700 kg synthetic urine-N ha–1) and the nitrification inhibitor DCD. We concluded that comammox Nitrospira Clade B: (1) was the most abundant comammox in the dairy pasture soil; (2) had a low tolerance to ammonium and can be inhibited by DCD; and (3) was not the dominant nitrite-oxidizer in the soil. This is the first study discovering a new subcluster of comammox Nitrospira Clade B2 from an agricultural soil.

Chemoresistance represents a major obstacle in breast cancer treatment. Bone morphogenetic protein 6 (BMP6) was reported to participate in the occurrence and development of various tumors. In the present study, the results of transcriptome sequencing, qRT-PCR and western blot analysis revealed that BMP6 was down-regulated in multidrug resistant MCF-7/Adr breast cancer cells and BMP6 overexpression sensitized MCF-7/Adr cells to chemotherapeutic drugs, indicating that BMP6 downregulation was involved in the mechanisms of multidrug resistance (MDR) of MCF-7/Adr breast cancer cells. GA-13315 (GA5) is a new tetracyclic diterpenoid selected from a series of gibberellin derivatives. Here, we found that GA5 exhibited more potent anti-tumor activity in multidrug resistant MCF-7/Adr breast cancer cells and xenografts, indicating that GA5 could overcome MDR. Mechanistically, GA5 increased BMP6 expression, and BPM6 knockdown partially reversed the inhibitory effect of GA5 on cell proliferation. Furthermore, we found that ERK phosphorylation and P-gp expression were increased in MCF-7/Adr cells when compared with MCF-7 cells. Either overexpression of BMP6 or treatment the cells with GA5 significantly decreased ERK phosphorylation and P-gp expression, indicating that GA5 reversed MDR of MCF-7/Adr cells by upregulating BMP6, thereby inhibiting the activation of ERK signaling pathway and reducing P-gp expression. Collectively, our present study demonstrated that the MDR of MCF-7/Adr cells was closely related to the low expression of BMP6, and revealed the molecular mechanisms by which GA5 overcame MDR in breast cancer, providing evidence in supporting the development of GA5 to be a promising agent for overcoming MDR in clinical cancer therapy in the future.

Background: Extramedullary disease is a manifestation of multiple myeloma, the prognosis of which remains poor even in the era of novel drugs. Therefore, we aimed to develop a predictive model for patients with primary extramedullary multiple myeloma (EMM).Methods: Clinical and laboratory data of patients diagnosed with primary EMM between July 2007 and July 2021 were collected and analyzed. Univariate and least absolute shrinkage and selection operation Cox regression analyses (LASSO) were used to select prognostic factors for overall survival (OS) to establish a nomogram prognostic model. The performance of the model was evaluated using concordance index which was internally validated by bootstraps with 1,000 resample, area under the curve (AUCs), and calibration curves.Results: 217 patients were included in this retrospective study. Patients with EMM had a higher rate of belonging to the male sex, age >50 years, advanced Durie–Salmon stage III, hypercalcemia, and low hemoglobin level. Compared with patients with bone-related extramedullary disease, those with extraosseous-related extramedullary disease had a higher frequency of advanced Durie–Salmon stage III, lower rate of hypercalcemia, and elevated prothrombin time. The OS and progression-free survival (PFS) of patients with bone-related extramedullary disease were significantly higher than those of patients with extraosseous-related extramedullary disease. After the univariate and LASSO analyses, six prognostic factors, including performance status, number of extramedullary involved sites, β2-microglobulin, lactate dehydrogenase, monocyte–lymphocyte ratio, and prothrombin time, were integrated to establish a nomogram. The model showed robust discrimination with a concordance index (C-index) of 0.775 (95% confidence interval [CI], 0.713–0.836), internally validated with the corrected C-index of 0.756, and excellent performance in time-dependent AUCs compared with other staging systems. The AUCs for 1-, 3-, and 5-year OS were 0.814, 0.744, and 0.832, respectively. The calibration curves exhibited good consistency between the observed and nomogram-predicted OS. The 5-year OS of patients in the high-risk group (23.3%; 95% CI, 13.9%–39.3%) was much worse than that in the low-risk group (73.0%; 95% CI, 62.5%–85.4%; p < 0.001).Conclusion: The nomogram predictive model based on six clinical variables showed good prognostic performance and could better predict individual survival in patients with EMM.

Klebsiella pneumoniae is a primary culprit of antibiotic-resistant nosocomial infections worldwide, and infections caused by NDM-producing strains are a major threat due to limited therapeutic options. The majority of blaNDM cases occur on plasmids; therefore, we explored the relationships between plasmids and blaNDM genes in K. pneumoniae by analyzing the variants of blaNDM, replicon types, conjugative transfer regions of 171 blaNDM-harboring plasmids from 4,451 K. pneumoniae plasmids. Of the nine identified blaNDM variants, blaNDM-1 (73.68%) and blaNDM-5 (16.37%) were the most dominant. Over half of the blaNDM-harboring plasmids of K. pneumoniae were classified into IncF plasmids. IncX3 single-replicon plasmids (46–57 kb) carried genes encoding relaxases of the MOBP family, T4CP genes of the VirD4/TraG subfamily, and VirB-like T4SS gene clusters, which were mainly geographically distributed in China. We found 10 blaNDM-harboring IncN plasmids (38.38–63.05 kb) carrying the NW-type origin of transfer (oriT) regions, genes coding for relaxases of MOBF family, genes encoding T4CPs of the TrwB/TraD subfamily, and Trw-like T4SS gene clusters, which were also mainly geographically distributed in China. Moreover, we identified 21 IncC plasmids carrying blaNDM-1 (140.1–329.2 kb), containing the A/C-type oriTs, genes encoding relaxases of MOBH family, genes encoding T4CPs belonging to TrwB/TraD subfamily, and Tra_F-like T4SS gene clusters. The blaNDM-harboring IncC plasmids were widely geographically distributed all over the world, mainly in the United States, China and Viet Nam. These findings enhance our understanding of the diversity of blaNDM-harboring plasmids in K. pneumoniae.

In this study, to optimize the Staphylococcus aureus control program, a meta-analysis was conducted to investigate the epidemiology and antimicrobial resistance (AMR) profile of S. aureus-associated bovine mastitis in China from 2000 to 2020. A total of 33 publications from PubMed, Google Scholar, and China National Knowledge Infrastructure (CNKI) database were included in our research, among which nine publications included the AMR test. The pooled prevalence of S. aureus was 36.23%, and subgroup analysis revealed that the prevalence dropped from 2000–2010 to 2011–2020, which shows that China is on the right track. The pooled AMR rate indicate isolates were most resistant to β-lactams (50.68%), followed by quinolones (36.23%), macrolides (34.08%), sulfonamides (32.25%), tetracyclines (27.83%), aminoglycosides (26.44%), lincosamides (23.39%), and amphenicol (10.33%). Both the pooled prevalence and AMR of S. aureus in China are higher than those in Western countries, such as Germany, Belgium, Ireland, and the United States—countries with a long animal husbandry history and good management. Thus, there is still room to improve the treatment of S. aureus-associated bovine mastitis in China.

BackgroundCircular RNAs (circRNAs) are receiving increasing attention as novel biomarkers. Our goal was to investigate the diagnostic, clinicopathological, and prognostic utility of circRNAs in prostate cancer (PCa).MethodsRelevant literature was searched in PubMed, Web of Science, and EMBASE. Sensitivity, specificity, diagnostic odds ratio (DOR), negative likelihood ratio (NLR), positive likelihood ratio (PLR), and the area under the curve (AUC) were calculated to evaluate the diagnostic accuracy of circRNA expression. circRNAs’ clinical, pathological, and prognostic value was examined using pooled odds ratios (ORs) and hazard ratios (HRs).ResultsThis meta-analysis included 23 studies, with 5 for diagnosis, 16 for clinicopathological parameters, and 10 for prognosis. For diagnostic value, the pooled sensitivity, pooled specificity, PLR, NLR, DOR, and AUC were 0.82, 0.62, 2.17, 0.29, 7.37, and 0.81, respectively. Upregulation of carcinogenic circRNAs was associated with poor clinical parameters (Gleason score: OR = 0.222, 95% CI: 0.145–0.340; T classification: OR = 0.274, 95% CI: 0.175–0.430; lymph node metastasis: OR = 0.353, 95% CI: 0.175–0.716; tumor size: OR = 0.226, 95% CI: 0.099–0.518) and could predict poor survival outcomes (HR = 2.408, 95% CI: 1.559–3.720, p < 0.001). Conversely, downregulation of tumor-suppressor circRNAs was also associated with poor clinical parameters (Gleason score: OR = 1.689, 95% CI: 1.144–2.493; T classification: OR = 2.586, 95% CI: 1.779–3.762) and worse prognosis (HR = 1.739, 95% CI: 1.147–2.576, p = 0.006).ConclusionOur results showed that circRNAs might be useful biomarkers for the diagnosis and prognosis of PCa.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021284785.