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Abstract Crizotinib carries an FDA hepatotoxicity warning, yet analysis of the FAERS database suggests that the severity of its hepatotoxicity risks, including progression to hepatitis and liver failure, might be underreported. However, the underlying mechanism remains poorly understood, and effective intervention strategies are lacking. Here, mRNA-sequencing analysis, along with KEGG and GO analyses, revealed that DEGs linked to Crizotinib-induced hepatotoxicity predominantly associate with the ferroptosis pathway which was identified as the principal mechanism behind Crizotinib-induced hepatocyte death. Furthermore, we found that ferroptosis inhibitors, namely Ferrostatin-1 and Deferoxamine mesylate, significantly reduced Crizotinib-induced hepatotoxicity and ferroptosis in both in vivo and in vitro settings. We have also discovered that overexpression of AAV8-mediated Nrf2 could mitigate Crizotinib-induced hepatotoxicity and ferroptosis in vivo by restoring the imbalance in glutathione metabolism, iron homeostasis, and lipid peroxidation. Additionally, both Stat1 deficiency and the Stat1 inhibitor NSC118218 were found to reduce Crizotinib-induced ferroptosis. Mechanistically, Crizotinib induces the phosphorylation of Stat1 at Ser727 but not Tyr701, promoting the transcriptional inhibition of Nrf2 expression after its entry into the nucleus to promote ferroptosis. Meanwhile, we found that MgIG and GA protected against hepatotoxicity to counteract ferroptosis without affecting or compromising the anti-cancer activity of Crizotinib, with a mechanism potentially related to the Stat1/Nrf2 pathway. Overall, our findings identify that the phosphorylation activation of Stat1 Ser727, rather than Tyr701, promotes ferroptosis through transcriptional inhibition of Nrf2, and highlight MgIG and GA as potential therapeutic approaches to enhance the safety of Crizotinib-based cancer therapy.

The objective of this study was to assess the differences in the quality of fried potato fries across various potato varieties (lines) in Qinghai Province, as well as to identify suitable potato varieties (lines) for the production of fried potato fries. Twenty-one representative potato varieties (lines) were selected as raw materials for the production of fried potato fries, and then their fundamental nutritional attributes and quality characteristics were evaluated. The suitability of the fried potato fries was assessed using principal component analysis, correlation analysis, and iterative clustering. The results revealed considerable differences in the nutritional indicators among different potato varieties (lines) in Qinghai Province. Principal component analysis identified five principal components, which accounted for 86.43% of the cumulative variance contribution rate. Leveraging the comprehensive scores from iterative clustering, three suitable potato varieties (lines) for processing fried potato fries were identified, namely, Qingshu 15, Qingshu 14, and Qing 11-2-9. Evaluation of their palatability characteristics demonstrated that the fried potato fries exhibited a crispy exterior and tender interior texture (sensory score of 62~73), favorable chewiness (52~53), and bright color (a* value of 4.0~6.5), aligning with practical applications. The results achieved efficient utilization of potato processing in Qinghai Province, which could meet consumer demand, and provided a theoretical basis for potato quality improvement and special variety breeding.

ABSTRACT: China has abundant local duck resource populations, and evaluating the characteristics of these breeds will help improve development and utilization. In this study, we conducted the first investigations of growth and slaughter performance on Sichuan Shelduck (n = 240), an endangered duck local breed. The average body weight is 1497.91 g at 90 d of age. According to the growth curve through data recorded every 2 wk, we observed a low relative growth rate (RGR) for the early growth stage. The RGR shows a decreasing trend with age increasing in the stage from 0 to 56 d of age. The SNP-based heritability estimation showed the growth rate has a relatively high heritability, indicating high genetic stability for this trait. In the correlation analysis, the percentage of leg muscle is positively correlated with the absolute growth rate (AGR) at 28 to 42 d of age, whereas it is negatively correlated with the earlier stages, exhibiting a time-specific correlation result. Additionally, genome-wide association studies (GWAS) identified PCSK6, TOX2, and TOMM7 as potential candidate genes influencing AGR (42–56) and AGR (56–90), while the candidate genes of slaughter traits were PTP4A2, FAM110B, TOX, UBXN2B, and FCHSD2. These results provide an important reference for further understanding the genetic basis of growth and meat production performance of Sichuan Shelduck.

AimThe purpose of this study was to explore the association between flavonoids intake and chronic low back pain (CLBP).MethodsThis cross-sectional study analyzed data from the National Health and Nutrition Examination Survey. Dietary flavonoids intake was assessed using a two-day recall questionnaire on dietary intake. CLBP was defined based of self-reported question. Weighted univariate and multivariate logistic regression models were performed to evaluate the relationship between flavonoids intake and CLBP. Additionally, subgroup analyses were conducted based on age, sedentary behavior time, arthritis, depression, and sleep disorder.ResultsA total of 3,136 adults were included, and 460 participants developed CLBP. After adjusting confounders, compared with the lowest total flavonoids intake tertile (reference group), flavonoids intake with highest tertile (>170 mg) was associated with reduced odds of CLBP [odds ratio (OR) =0.74, 95% confidence interval (CI): 0.57–0.95]. This relationship of flavonoids intake with CLBP remained statistically significant among participants aged ≥45 years (OR = 0.52, 95%CI: 0.35–0.76), with sedentary behavior time of >3 h (OR = 0.60, 95%CI: 0.41–0.86), with arthritis (OR = 0.51, 95%CI: 0.29–0.90), depression (OR = 0.48, 95%CI: 0.24–0.98), and sleep disorder (OR = 0.27, 95%CI: 0.12–0.60).ConclusionHigher flavonoids intake was found to be negatively associated with the likelihood of CLBP. For the general adult population, consuming foods rich in flavonoids may be linked to a reduced risk of CLBP.

ABSTRACT: The primary feathers of ducks have important economic value in the poultry industry. This study quantified the primary feather phenotype of Nonghua ducks, including the primary feathers' length, area, distribution of black spots, and feather symmetry. And genome-wide association analysis was used to screen candidate genes that affect the primary feather traits. The genome-wide association study (GWAS) results identified the genetic region related to feather length (FL) on chromosome 2. Through Linkage disequilibrium (LD) analysis, candidate regions (chr2: 115,246,393–116,501,448 bp) were identified and were further annotated to 5 genes: MRS2, GPLD1, ALDH5A1, KIAA0319, and ATP9B. Secondly, candidate regions related to feather black spots were identified on chromosome 21. Through LD analysis, the candidate regions (chr21: 163,552–2,183,853 bp) were screened and further annotated to 47 genes. Among them, STK4, CCN5, and YWHAB genes were related to melanin-related pathways or pigment deposition, which may be key genes affecting the distribution of black spots on feathers. In addition, we also screened 125 genes on multiple chromosomes that may be related to feather symmetry. Among them, significant SNPs on chromosome 1 were further identified as candidate regions (chr1: 142,118,209–142,223,605 bp) through LD analysis and annotated into 2 genes, TGFBRAP1 and LOC113839965. These results reported the genetic basis of the primary feather from multiple phenotypes, and offered valuable insights into the genetic basis for the growth and development of duck feathers and feather color pattern.

In order to explore the effects of ecological landscaping tree species Taxodium ‘Zhongshanshan 118’ on soil microbial ecosystem in Huaihe Plain of north Anhui Province, the differences in soil nutrients levels, microbial communities structures and their influencing factors between the rhizosphere (R) and non-rhizosphere (NR) were analyzed. The results were as follows: (1) The 4-year-old Taxodium ‘Zhongshanshan 118’ rhizosphere had a low enrichment capacity for macronutrients, resulting in a deficiency of hydrolyzable nitrogen and available phosphorus. The R had similar levels of total nitrogen, and lower levels of total phosphorus, total potassium and available potassium than the NR soil. The R had a strong enrichment ability for microelements (iron, copper, manganese). And the available manganese content in the R was significantly higher than that in the NR. Both the R and the NR soils of Taxodium ‘Zhongshanshan 118’ were alkaline. The R had a slightly lower pH and a higher electrical conductivity than the NR. The R had a certain degree of enrichment for available sodium, available magnesium and available calcium, as well as for organic carbon and organic matter. (2) Based on the Anosim analysis of community structure between groups, the R value was 0.224 (P=0.022), which was significantly greater than 0, indicating significant differences between the bacterial communities of the R and the NR of Taxodium ‘Zhongshanshan 118’. The total number of OTUs in the R and the NR was 5 283. There were 1 307 unique OTUs in R and 1 265 OTUs in NR. (3) The R had a slightly lower bacterial diversity than the NR. The dominant phylum in both the R and the NR were Firmicutes, Proteobacteria, Acidobacteriota, Bacteroidetes, Chloroflexi, Myxococcota, Actinobacteria, and Crenarchaeota. Among them, only Acidobacteriota showed a significant positive correlation with available phosphorus. The R had higher abundances of Firmicutes (17.94%) and Bacteroidetes (5.21%) than the NR (1.84% and 3.90%), respectively. Neither of them had a significant correlation with environmental factors. The R had higher abundances of Clostridia, Bacteroidia and Bacilli than the NR by 14.05%, 1.32% and 2.06%, respectively. (4) The UPGMA clustering analysis showed that R4 was isolated from the other samples. NR4 and NR5 formed a cluster, NR1, NR2 and NR3 clusted with R1, R2, R3 and R5. R4 had lower species diversity and abundance than the other samples, and had an uneven distribution of taxa. In conclusion, despite the weak rhizosphere effect of young Taxodium ‘Zhongshanshan 118’, it was the main factor for the enrichment of Firmicutes and Bacteroidetes in the rhizosphere. And more microelements and a moderate amount of macroelements should be applied in the cultivation process.

Abstract Background Amino acids are the basic components of protein and an important index to evaluate meat quality. With the rapid development of genomics, candidate regions and genes affecting amino acid content in livestock and poultry have been gradually revealed. Hence, genome-wide association study (GWAS) can be used to screen candidate loci associated with amino acid content in duck meat. Result In the current study, the content of 16 amino acids was detected in 358 duck breast muscles. The proportion of Glu to the total amino acid content was relatively high, and the proportion was 0.14. However, the proportion of Met content was relatively low, at just 0.03. By comparative analysis, significant differences were found between males and females in 3 amino acids, including Ser, Met, and Phe. In addition, 12 SNPs were significantly correlated with Pro content by GWAS analysis, and these SNPs were annotated by 7 protein-coding genes; 8 significant SNPs were associated with Tyr content, and these SNPs were annotated by 6 protein-coding genes. At the same time, linkage disequilibrium (LD) analysis was performed on these regions with significant signals. The results showed that three SNPs in the 55–56 Mbp region of chromosome 3 were highly correlated with the leader SNP (chr3:55526954) that affected Pro content (r 2 > 0.6). Similarly, LD analysis showed that there were three SNPs in the 21.2–21.6 Mbp region of chromosome 13, which were highly correlated with leader SNP (chr13:21421661) (r 2 > 0.6). Moreover, Through functional enrichment analysis of all candidate genes. The results of GO enrichment analysis showed that several significant GO items were associated with amino acid transport function, including amino acid transmembrane transport and glutamine transport. The results further indicate that these candidate genes are closely associated with amino acid transport. Among them, key candidate genes include SLC38A1. For KEGG enrichment analysis, CACNA2D3 and CACNA1D genes were covered by significant pathways. Conclusion In this study, GWAS analysis found a total of 28 significant SNPs affecting amino acid content. Through gene annotation, a total of 20 candidate genes were screened. In addition, Through LD analysis and enrichment analysis, we considered that SERAC1, CACNA2D3 and SLC38A1 genes are important candidate genes affecting amino acid content in duck breast muscle.

Objective To explore the histomorphology and related indicators in a rat model of skeletal muscle injury in an artificial experimental chamber as special environment in Northwest China to stimulate a hot and dry desert environment in order to screen the evaluation indicators of skeletal muscle injury in a hot and dry environment. Methods Eighteen male SD rats (8 weeks old) were randomly divided into blank control group (room temperature, free movement), room temperature exercise group, and hot and dry exercise group, with 6 rats in each group.After the rats were subjected to adaptation training for 3 d (a 3-D exercise treadmill, speed: 16 m/min, slope: -16°, time: 5~10 min), the rats in the 2 exercise groups were subjected to a treadmill once per day at a speed of 19.3 m/min and a slope of-16° till the end of exhaustion, and those in the hot and dry exercise group were housed in an artificial experimental chamber at a temperature of (40±1)℃, a humidity of (10±2)%.After 6 d of continuous exercise, the rat soleus muscle tissue was taken to observe the pathological changes, and the serum samples were detected for skeletal muscle injury markers, inflammatory factors, oxidative stress related factors, hormones and other related indicators. Results When compared with the blank control group and the room temperature exercise group, the hot and dry exercise group had significantly higher concentrations of creatine kinase (CK), creatine kinase isoenzyme (CK-MB) and myotype creatine kinase (CK-MM)(P < 0.05), elevated contents of TNF-α, IL-1β and IL-6(P < 0.05), raised malondialdehyde (MDA) content and lower superoxide dismutase (SOD) activity (P < 0.05), lower testosterone (T) but higher corticosterone (Cort) levels and thus lower testosterone/corticosterone (T/Cort) ratio (P < 0.05).The markers of skeletal muscle injury, CK, CK-MB and CK-MM were positively correlated with the pro-inflammatory cytokines, TNF-α, IL-1β and IL-6(P < 0.05), positively with the antioxidant indicator MDA but negatively with SOD (P < 0.05), and positively correlated with Cort level and negatively with T level and T/Cort ratio (P < 0.05). Conclusion A stable rat model of skeletal muscle injury in a hot and dry desert environment is successfully constructed.The severity of skeletal muscle injury is greater in rats in a hot and dry desert environment than those in a normal temperature environment.TNF-α and IL-1β are found to be indirect indicators to evaluate skeletal muscle injury in the environment.

Abstract Pancreatic cancer is one of the most malignant tumor types and is characterized by high metastasis ability and a low survival rate. As a chromatin-binding protein, HMGA2 is widely overexpressed and considered an oncogene with various undefined regulatory mechanisms. Herein, we demonstrated that HMGA2 is highly expressed in pancreatic cancer tissues, mainly distributed in epithelial cells, and represents a subtype of high epithelial–mesenchymal transition. Deletion of HMGA2 inhibits tumor malignancy through cell proliferation, metastasis, and xenograft tumor growth in vivo. Moreover, HMGA2 enhanced the cellular redox status by inhibiting reactive oxygen species and promoting glutathione production. Importantly, ferroptotic cell death was significantly ameliorated in cells overexpressing HMGA2. Conversely, HMGA2 deletion exacerbated ferroptosis. Mechanistically, HMGA2 activated GPX4 expression through transcriptional and translational regulation. HMGA2 binds and promotes cis-element modification in the promoter region of the GPX4 gene by enhancing enhancer activity through increased H3K4 methylation and H3K27 acetylation. Furthermore, HMGA2 stimulated GPX4 protein synthesis via the mTORC1-4EBP1 and -S6K signaling axes. The overexpression of HMGA2 alleviated the decrease in GPX4 protein levels resulting from the pharmacologic inhibition of mTORC1. Conversely, compared with the control, HMGA2 deletion more strongly reduced the phosphorylation of 4EBP1 and S6K. A strong positive correlation between HMGA2 and GPX4 expression was confirmed using immunohistochemical staining. We also demonstrated that HMGA2 mitigated the sensitivity of cancer cells to combination treatment with a ferroptosis inducer and mTORC1 inhibition or gemcitabine. In summary, our results revealed a regulatory mechanism by which HMGA2 coordinates GPX4 expression and underscores the potential value of targeting HMGA2 in cancer treatment.

Background Nocturnal blood pressure (BP) is correlated with an increased risk of cardiovascular events and is an important predictor of cardiovascular death in hypertensive patients.Objective Nocturnal BP control is of great importance for cardiovascular risk reduction. This systematic review and meta-analysis aimed to explore the efficacy of angiotensin receptor blockers (ARBs) for nocturnal BP reduction in patients with mild to moderate hypertension.Methods PICOS design structure was used to formulate the data extraction. All statistical calculations and analyses were performed with R.Results Seventy-seven studies with 13,314 participants were included. The overall analysis indicated that nocturnal BP drop varied considerably among different ARBs. Allisartan (13.04 [95% CI (−18.41, −7.68)] mmHg), olmesartan (11.67 [95% CI (−14.12, −9.21)] mmHg), telmisartan (11.11 [95% CI (−12.12, −10.11)] mmHg) were associated with greater reduction in nocturnal systolic BP. In the aspect of the nocturnal-diurnal BP drop ratio, only allisartan was greater than 1. While, the variation tendency of last 4–6 h ambulatory BP was basically consistent with nocturnal BP. Additionally, allisartan showed improvement effect in the proportion of patients with dipping BP pattern.Conclusions This study demonstrates that for patients with mild to moderate hypertension, allisartan, olmesartan and telmisartan have more advantages in nocturnal BP reduction among the ARBs, while allisartan can reduce nighttime BP more than daytime BP and improve the dipping pattern.

Objective To investigate the clinical characteristics of indolent B-cell non-Hodgkin lymphoma (iB-NHL) with monoclonal immunoglobulin (McIg). Methods The clinical and pathological data of 82 newly diagnosed iB-NHL patients in the Affiliated Hospital of Nantong University from November 2013 to October 2021 were retrospectively analyzed. According to the results of serum immunofixation electrophoresis (SIFE), they were divided into McIg positive group (30 cases) and negative group (52 cases). The clinical characteristics, laboratory examination results and overall survival (OS) were analyzed. Results iB-NHL with McIg were more common in males, with IgM-κ being the most common, and the clinical stage was mostly stage Ⅲ-Ⅳ, with marginal zone lymphoma (MZL) as the main stage. Compared with the negative group, patients in the positive group were more likely to have bone marrow infiltration, international prognostic index (IPI)≥3, decreased white blood cell count, anemia, hypoalbuminemia, elevated globulin and cystatin C (P＜0.05). Cox univariate analysis showed that IPI≥3 and McIg positivity were associated with worse OS in patients. Multivariate analysis showed that McIg positivity was an independent adverse prognostic factor for OS of patients (HR=0.074, 95%CI: 0.009-0.609, P=0.015). Follow-up ended on October 31, 2021. The median OS of the positive group was 52 months, but the median OS of the patients without McIg was not reached, and the difference of OS between two groups had statistical significance (P＜0.01). Conclusion Among the newly diagnosed patients with iB-NHL, the prognosis of patients with McIg is relatively poor, which needs to be paid more attention in clinical diagnosis and treatment.

Objective: Percutaneous nephrolithotomy (PCNL) is the main method for pyonephrosis or lithotripsy in urology. However, it often comes with high risk, as the inaccurate puncture inevitably causes bleeding, intra- and post-operative complications. So, a new inter-disciplinary approach is needed to perform the puncture more accurately. Methods: 3 signs made of lead were marked onto the skin of the posterior side of the waist of a domestic pig or a patient, which was scanned by computed tomography (CT). Based on the CT images, the computer design and the 3D printing, a navigation template made of the transparent resin material is constructed. They were attached onto the surgical area on pig or patient according to the signs. During the PCNL, with this template, the puncture position, angle and depth were optimized in order to precisely enter the targeted renal pelvis or calices. Results: With the 3D navigation templates, 18G puncture needles were used to enter the renal pelvis upon performing the PCNL on a porcine model and a patient. On the porcine model, the urine outflow was observed with minimal complication. Post-operative CT scans revealed that the needle was located in the renal pelvis. For the patient case, the puncture point was designed to target the calix with stone. No obvious bleeding and complication was found in renal puncture with template. Conclusions: The navigation template was made with the combination of 3D printing, CT images and computer design. This template allows for accurate puncture of the renal pelvis or calix. Surgical improvement in kidney stones and pyonephrosis was observed in porcine model and patient case. In the future, prospective, trandomized, controlled clinical trials are needed to further confirm its advantage.

Colorectal cancer is one of the most common malignancies and ranks second in terms of cancer-related mortality worldwide due to its metastasis, drug resistance, and reoccurrence. High-mobility gene group A2 (HMGA2) is overexpressed in colorectal cancer, contributing to the aggressiveness of tumor malignance, and promotes drug resistance in many types of cancer. However, the underlying molecular mechanism of HMGA2 is yet to be elucidated. In this study, we showed that HMGA2 is overexpressed in colorectal cancer tissue, and knockdown of HMGA2 significantly inhibited colorectal cancer cell growth and migratory capability. HMGA2 regulates the cancer cell response to a widely used anti-cancer drug, paclitaxel (PTX). HMGA2 knockdown increased cell death, whereas HMGA2 overexpression decreased cell death after PTX treatment. Furthermore, lower reactive oxygen species (ROS) levels and mitochondrial potential were detected in HMGA2 overexpression cells after PTX treatment. However, HMGA2 knockdown produced the opposite effect. RNA sequencing showed a p53 signaling pathway-dependent regulation in HMGA2 knockdown cells. Combined with p53 inhibitors and HMGA2 knockdown, a synergetic effect of more cell death was observed in colorectal cancer cells after PTX treatment. Thus, we showed that HMGA2 can activate p53 signaling to regulate colorectal cancer cell death after PTX treatment. Altogether, our results reveal novel insights into the molecular mechanisms underlying HMGA2-mediated cancer cell resistance against PTX and highlight the potential of targeting HMGA2 and p53 signaling for the therapeutic investigation of colorectal cancer.

In order to explore the species and population distribution of endophytic fungi in Camellia luteoflora, as well as their inhibitory effects on plant pathogenic fungi, this study used tissue separation method to isolate and purify endophytic fungi in C. luteoflora. These fungi were identified based on morphology and molecular biology, and their diversity was evaluated through statistical analysis. The strains with antibacterial activity were screened out by the plate confrontation method. The results were as follows: (1) A total of 261 strains of endophytic fungi were isolated from 324 C. luteoflora tissue samples, belonging to 1 phylum, 5 classes, 9 orders, and 22 genera. The dominant genera were Colletotrichum, Diaporthe and Pestalotiopsis with isolation frequencies of 21.84%, 16.86% and 10.34%, respectively. (2) The distribution of endophytic fungi in C. luteoflora varied in different seasons. The highest number of strains was isolated in winter (72 strains, accounting for 27.59%, belonging to 16 genera), 62 strains were isolated in spring (belonging to 13 genera), 59 strains were isolated in summer (belonging to 15 genera), and 68 strains were isolated in autumn (belonging to 13 genera). The Shannon-Wiener index (H′), Simpson index (D), Pielou's evenness index (E), and Margalef's richness index (M) were the highest in winter. The similarity of endophytic fungal species between spring and winter was higher, and the similarity between summer and autumn was higher. (3) The distribution of endophytic fungi also varied in different parts of C. luteoflora. The stems had the most abundant endophytic fungi, with 102 strains accounting for 39.08% (belonging to 15 genera), 61 strains were isolated from the roots (belonging to 10 genera), and 98 strains were isolated from the leaves (belonging to 15 genera). The H′, D, E, and M were highest in the stems, and the endophytic fungal species in the leaves were most similar to those in the stems. (4) The plate confrontation results showed that among the 35 tested endophytic fungi, 26 endophytic fungi had inhibitory effects on at least one plant pathogenic fungi, accounting for 74.29%, among which CJ-Ⅱ-2, XY-V-3, QY-Ⅱ-4, QJ-Ⅲ-2 and DJ-I-2 had inhibitory effects on eight plant pathogen fungi to varying degrees. XY-V-3 had the best inhibitory effect on eight plant pathogenic fungi, and the inhibitory rate was higher than 50%. XY-V-3 and QJ-Ⅲ-2 have higher inhibitory rate than 50% on two strains of pathogenic fungi in C. luteoflora, which had the potential to control disease of C. luteoflora. To sum up, the diversity of endophytic fungi in C. luteoflora is rich, and some of the strains have higher effect of inhibiting plant pathogenic fungi, which lay a foundation for the research and development of biological control products and the disease control of C. luteoflora.

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia in the elderly worldwide. The exact etiology of AD, particularly its genetic mechanisms, remains incompletely understood. Traditional genome-wide association studies (GWAS), which primarily focus on single-nucleotide polymorphisms (SNPs) with main effects, provide limited explanations for the “missing heritability” of AD, while there is growing evidence supporting the important role of epistasis. In this study, we performed a genome-wide SNP–SNP interaction detection using a linear regression model and employed multiple GPUs for parallel computing, significantly enhancing the speed of whole-genome analysis. The cerebrospinal fluid (CSF) phosphorylated tau (P-tau)/amyloid- $$\beta _{42}$$ β 42 (A $$\beta _{42}$$ β 42 ) ratio was used as a quantitative trait (QT) to enhance statistical power. Age, gender, and clinical diagnosis were included as covariates to control for potential non-genetic factors influencing AD. We identified 961 pairs of statistically significant SNP–SNP interactions, explaining a high-level variance of P-tau/A $$\beta _{42}$$ β 42 level, all of which exhibited marginal main effects. Additionally, we replicated 432 previously reported AD-related genes and found 11 gene–gene interaction pairs overlapping with the protein-protein interaction (PPI) network. Our findings may contribute to partially explain the “missing heritability” of AD. The identified subnetwork may be associated with synaptic dysfunction, Wnt signaling pathway, oligodendrocytes, inflammation, hippocampus, and neuronal cells.

Abstract This paper investigates Regional Integrated Energy Systems (RIES), emphasizing the connection of diverse energy supply subsystems to address varied user needs and enhance operational efficiency. A novel low-carbon economic dispatch method, utilizing the multi-objective chaotic artificial hummingbird algorithm, is introduced. The method not only optimizes economic and environmental benefits but also aligns with "carbon peak and carbon neutrality" objectives. The study begins by presenting a comprehensive low-carbon economic dispatch model, followed by the proposal of the multi-objective chaotic artificial hummingbird algorithm, crucial for deriving the Pareto frontier of the low-carbon economic dispatch model. Additionally, we introduce a TOPSIS approach based on combined subjective and objective weights, this approach harnesses the objective data from the Pareto solution set deftly, curbs the subjective biases of dispatchers effectively and facilitates the selection of an optimal system operation plan from the Pareto frontier. Finally, the simulation results highlight the outstanding performance of our method in terms of optimization outcomes, convergence efficiency, and solution diversity. Noteworthy among these results is an 8.8% decrease in system operational economic costs and a 14.2% reduction in carbon emissions.

Abstract Background Regional anesthesia with ultrasound-guided brachial plexus block is widely used for patients undergoing shoulder and upper limb surgery, but needle misplacement can result in complications. The purpose of this study was to develop and validate a convolutional neural network (CNN) model for segmentation of the brachial plexus at the interscalene level. Methods This prospective study included patients who underwent ultrasound-guided brachial plexus block in the Anesthesiology Department of Beijing Jishuitan Hospital between October 2019 and June 2022. A Unet semantic segmentation model was developed to train the CNN to identify the brachial plexus features in the ultrasound images. The degree of overlap between the predicted segmentation and ground truth segmentation (manually drawn by experienced clinicians) was evaluated by calculation of the Dice index and Jaccard index. Results The final analysis included 502 images from 127 patients aged 41 ± 14 years-old (72 men, 56.7%). The mean Dice index was 0.748 ± 0.190, which was extremely close to the threshold level of 0.75 for good overlap between the predicted and ground truth segregations. The Jaccard index was 0.630 ± 0.213, which exceeded the threshold value of 0.5 for a good overlap. Conclusion The CNN performed well at segregating the brachial plexus at the interscalene level. Further development could allow the CNN to be used to facilitate real-time identification of the brachial plexus during interscalene block administration. Clinical trial registration The trial was registered prior to patient enrollment at the Chinese Clinical Trial Registry (ChiCTR2200055591), the site url is https://www.chictr.org.cn/ . The date of trial registration and patient enrollment is 14/01/2022.

Objectives: Lung cancer is the leading cause to induce cancer-related mortality. Effective biomarkers for prediction the occurrence of lung cancer is urgently needed. Our previous studies indicated that pyroptosis-related cytokines TNF-α, IFN-γ, MIP-1α, MIP-1β, MIP-2 and IP-10 is important to influence the efficacy of chemotherapy drug in lung cancer tissues. But the role of pyroptosis-related cytokines in prediction the occurrence of lung cancer is still unknown. Methods: Blood samples were collected from 258 lung cancer patients at different stage and 80 healthy volunteers. Serum levels of pyroptosis-related cytokines including TNF-α, IFN-γ, MIP-1α, MIP-1β, MIP-2 and IP-10 were measured by Cytometric Bead Array (CBA). ROC curve was performed to evaluate the cut-off value and diagnosis value for prediction and diagnosis of lung cancer. Results: Compared with control group, the levels of IP-10, MIP-1α, MIP-1β, MIP-2 and TNF-α were significantly higher in lung cancer patients (45.5 (37.1–56.7): 57.2 (43.0–76.5), 34.4 (21.8–75.2): 115.4 (96.6–191.2), 49.3 (25.6–78.7): 160.5 (124.9–218.6), 22.6 (17.8–31.2): 77.9 (50.1–186.5), 3.80 (2.3–6.2): 10.3 (5.7–16.6)), but the level of IFN-γ was decreased in the patients (12.38 (9.1–27.8): 5.9 (3.5–9.7)). All the above cytokines were significantly associated with the diagnosis of lung cancer, and the AUC values of IFN-γ, IP-10, MIP-1α, MIP-1β, MIP-2, and TNF-α were 0.800, 0.656, 0.905, 0.921, 0.914, and 0.824. And the AUC can rise to 0.986 after combining the above factors, and the sensitivity and specificity also up to 96.7 % and 93.7 %, respectively. Additionally, TNF-α (r = 0.400, P

ABSTRACT: Endogenous retroviruses (ERV) are viral genomes integrated into the host genome and can be stably inherited. Although ERV sequences have been reported in some avian species’ genome, the duck endogenous retroviruses (DERV) genome has yet to be quantified. This study aimed to identify ERV sequences and characterize genes near ERVs in the duck genome by utilizing LTRhavest and LTRdigest tools to forecast the duck genome and analyze the distribution of ERV copies. The results revealed 1,607, 2,031, and 1,908 full-length ERV copies in the Pekin duck (ZJU1.0), Mallard (CAU_wild_1.0), and Shaoxing duck (CAU_laying_1.0) genomes, respectively, with average lengths of 7,046, 7,027, and 6,945 bp. ERVs are mainly distributed on the 1, 2, and sex chromosomes. Phylogenetic analysis demonstrated the presence of Betaretrovirus in 3 duck genomes, whereas Alpharetrovirus was exclusively identified in the Shaoxing duck genome. Through screening, 596, 315, and 343 genes adjacent to ERV were identified in 3 duck genomes, respectively, and their functions of ERV neighboring genes were predicted. Functional enrichment analysis of ERV-adjacent genes revealed enrichment for Focal adhesion, Calcium signaling pathway, and Adherens junction in 3 duck genomes. The overlapped genes were highly expressed in 8 tissues (brain, fat, heart, kidney, liver, lung, skin, and spleen) of 8-wk-old Mallard, revealing their important expression in different tissues. Our study provides a new perspective for understanding the quantity and function of DERVs, and may also provide important clues for regulating nearby genes and affecting the traits of organisms.

ABSTRACT: The cage-rearing model of the modern poultry industry makes the bones of birds, especially egg-laying birds, more vulnerable to fracture, which poses serious damage to the health of birds. Research confirms that genetic material plays an important role in regulating bone growth, development, and remodeling. However, the genetic architecture underlying bone traits is not well understood. The objectives of this study are to identify valuable genes and genetic markers through a genome-wide association study (GWAS) for breeding to improve the duck bone quality. First, we quantified the tibia and femur quality traits of 260 laying ducks. Based on GWAS, a total of 75 SNP loci significantly associated with bone quality traits were identified, and 67 potential candidate genes were annotated. According to gene function analysis, genes P4HA2, WNT3A, and BST1 et al may influence bone quality by regulating bone cell activity, calcium and phosphate metabolism, or bone collagen maturation and cross-linking. Meanwhile, combined with the transcriptome results, we found that HOXB cluster genes are also important in bone growth and development. Therefore, our findings were helpful in further understanding the genetic architecture of the duck bone quality and provided a worthy theoretical basis and technological support to improve duck bone quality by breeding.

Clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)-mediated genome editing has greatly accelerated progress in plant genetic research and agricultural breeding by enabling targeted genomic modifications. Moreover, the prime editing system, derived from the CRISPR/Cas system, has opened the door for even more precise genome editing. Prime editing has the capability to facilitate all 12 types of base-to-base conversions, as well as desired insertions or deletions of fragments, without inducing double-strand breaks and requiring donor DNA templet. In a short time, prime editing has been rapidly verified as functional in various plants, and can be used in plant genome functional analysis as well as precision breeding of crops. In this review, we summarize the emergence and development of prime editing, highlight recent advances in improving its efficiency in plants, introduce the current applications of prime editing in plants, and look forward to future prospects for utilizing prime editing in genetic improvement and precision molecular breeding.

Cancer is a leading cause of human death worldwide, and the modulation of the metabolic properties of T cells employed in cancer immunotherapy holds great promise for combating cancer. As a crucial factor, energy metabolism influences the activation, proliferation, and function of T cells, and thus metabolic reprogramming of T cells is a unique research perspective in cancer immunology. Special conditions within the tumor microenvironment and high-energy demands lead to alterations in the energy metabolism of T cells. In-depth research on the reprogramming of energy metabolism in T cells can reveal the mechanisms underlying tumor immune tolerance and provide important clues for the development of new tumor immunotherapy strategies as well. Therefore, the study of T cell energy metabolism has important clinical significance and potential applications. In the study, the current achievements in the reprogramming of T cell energy metabolism were reviewed. Then, the influencing factors associated with T cell energy metabolism were introduced. In addition, T cell energy metabolism in cancer immunotherapy was summarized, which highlighted its potential significance in enhancing T cell function and therapeutic outcomes. In summary, energy exhaustion of T cells leads to functional exhaustion, thus resulting in immune evasion by cancer cells. A better understanding of reprogramming of T cell energy metabolism may enable immunotherapy to combat cancer and holds promise for optimizing and enhancing existing therapeutic approaches.

ABSTRACT: Allometric growth of the forelimb and hindlimb is a widespread phenomenon observed in vertebrates. As a typical precocial bird, ducks exhibit more advanced development of their hindlimbs compared to their forelimbs, enabling them to walk shortly after hatching. This phenomenon is closely associated with the development of long bones in the embryonic stage. However, the molecular mechanism governing the allometric growth of duck forelimb and hindlimb bones is remains elusive.In this study, we employed phenotypic, histological, and gene expression analyses to investigate developmental differences between the humerus (forelimb bone) and tibia/femur (hindlimb bones) in duck embryos. Our results revealed a gradual increase in weight and length disparity between the tibia and humerus from E12 to E28 (embryo age). At E12, endochondral ossification was observed solely in the tibia but not in the humerus. The number of differentially expressed genes (DEGs) gradually increased at H12 vs. T12, H20 vs. T20, and H28 vs. T28 stages consistent with phenotypic variations. A total of 38 DEGs were found across all 3 stages. Protein-protein interaction network analysis demonstrated strong interactions among members of HOXD gene family (HOXD3/8/9/10/11/12), HOXB gene family (HOXB8/9), TBX gene family (TBX4/5/20), HOXA11, SHOX2, and MEIS2. Gene expression profiling indicated higher expression levels for all HOXD genes in the humerus compared to tibia while opposite trends were observed for HOXA/HOXB genes with low or no expression detected in the humerus. These findings suggest distinct roles played by different clusters within HOX gene family during skeletal development regulation of duck embryo's forelimbs versus hind limbs. Notably, TBX4 exhibited high expression levels specifically in tibia whereas TBX5 showed similar patterns exclusively within humerus as seen previously across other species’ studies. In summary, this study identified key regulatory genes involved in allometric growth of duck forelimb and hindlimb bones during embryonic development. Skeletal development is a complex physiological process, and further research is needed to elucidate the regulatory role of candidate genes in endochondral ossification.

Abstract In recent years, bacteria have gained considerable attention as a promising drug carrier that is critical in improving the effectiveness and reducing the side effects of anti‐tumor drugs. Drug carriers can be utilised in various forms, including magnetotactic bacteria, bacterial biohybrids, minicells, bacterial ghosts and bacterial spores. Additionally, functionalised and engineered bacteria obtained through gene engineering and surface modification could provide enhanced capabilities for drug delivery. This review summarises the current studies on bacteria‐based drug delivery systems for anti‐tumor therapy and discusses the prospects and challenges of bacteria as drug carriers. Furthermore, our findings aim to provide new directions and guidance for the research on bacteria‐based drug systems.

Aberrant expression of adipogenic regulatory factors (ADIRF) in tumor cells is critical for tumor growth and metastasis. N6-methyladenosine (m6A) modifications have an important role in a variety of biological activities. Our study aimed to investigate the role of ADIRF in adenocarcinoma and to elucidate the regulatory role of m6A signaling on ADIRF. Differential expression of genes in tumor and normal tissues was analyzed using the LUAD dataset (GSE1987). The Kaplan-Meier method and receiver operating characteristic (ROC) curve analysis were performed to evaluate the prognostic and diagnostic value of ADIRF in LUAD. Loss-of-function or gain-of-function experiments were performed to study the effect of ADIRF on LUAD growth in vitro. The molecular mechanism of action of ADIRF in LUAD was confirmed using a dual-luciferase reporter system and MeRIP-qPCR. We identified a loss of ADIRF expression in LUAD tissues and cells. Furthermore, the restoration of ADIRF levels attenuated LUAD cell growth and metastasis in vitro. Mechanistically, an m6A “eraser,” α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5), eliminated the ADIRF m6A modification motif and further blocked the binding of the YTH domain-containing 2 (YTHDC2)-binding protein to ADIRF. At the molecular level, ALKBH5 enrichment increased ADIRF mRNA levels and prevented the attenuation of ADIRF mRNA by YTHDC2. The effects of ALKBH5 overexpression could also extend to the inhibition of LUAD cell proliferation and metastasis. This study linked ADIRF with the m6A modifying regulators ALKBH5 and YTHDC2, providing a promising molecular intervention for LUAD and deepening the understanding of LUAD mechanisms.

Abstract Background The genetic locus responsible for duck body size has been fully explained before, but the growth trait-related genetic basis is still waiting to be explored. For example, the genetic site related to growth rate, an important economic trait affecting marketing weight and feeding cost, is still unclear. Here, we performed genome wide association study (GWAS) to identify growth rate-associated genes and mutations. Result In the current study, the body weight data of 358 ducks were recorded every 10 days from hatching to 120 days of age. According to the growth curve, we evaluated the relative and absolute growth rates (RGR and AGR) of 5 stages during the early rapid growth period. GWAS results for RGRs identified 31 significant SNPs on autosomes, and these SNPs were annotated by 24 protein-coding genes. Fourteen autosomal SNPs were significantly associated with AGRs. In addition, 4 shared significant SNPs were identified as having an association with both AGR and RGR, which were Chr2: 11483045 C>T, Chr2: 13750217 G>A, Chr2: 42508231 G>A and Chr2: 43644612 C>T. Among them, Chr2: 11483045 C>T, Chr2: 42508231 G>A, and Chr2: 43644612 C>T were annotated by ASAP1, LYN and CABYR, respectively. ASAP1 and LYN have already been proven to play roles in the growth and development of other species. In addition, we genotyped every duck using the most significant SNP (Chr2: 42508231 G>A) and compared the growth rate difference among each genotype population. The results showed that the growth rates of individuals carrying the Chr2: 42508231 A allele were significantly lower than those without this allele. Moreover, the results of the Mendelian randomization (MR) analysis supported the idea that the growth rate and birth weight had a causal effect on the adult body weight, with the growth rate having a greater effect size. Conclusion In this study, 41 SNPs significantly related to growth rate were identified. In addition, we considered that the ASAP1 and LYN genes are essential candidate genes affecting the duck growth rate. The growth rate also showed the potential to be used as a reliable predictor of adult weight, providing a theoretical reference for preselection.

ObjectiveTo compare the differences between residents who did and who did not participate in a community colorectal cancer screening based on the results of their colorectal colonoscopy and explore the reasons.MethodsThe residents who underwent a colonoscopy in a central hospital in Shanghai from 2017 to 2020 were divided into two groups according to whether they had been screened in the community， and t test and χ2 test were used to compare the results of the colonoscopy （detection of lesions） of the examinees with different ages， genders， whether they had a history of colorectal cancer， and whether they had been screened in the community. The correlation between whether they had participated in the community screening and the detection of lesions was analyzed by the logistic regression model.ResultsFrom 2017 to 2020， the hospital had performed a colonoscopy for 6 389 people， and 3 623 lesions were detected， with a detection rate of 56.71%. There were 413 residents who had been screened in the community， accounting for 6.46% of the total number of those receiving a colonoscopy. 243 patients were found with pathological changes， with a detection rate of 58.84%. Compared with the residents who did not participate in the community screening， the proportion of adenoma and polyp was higher in those who had participated in the screening （χ2=50.44， P

Background: The prevalence of prehypertension and hypertension has been increasing over the years, and is closely related to cardiovascular and cerebrovascular diseases. Exercise is an effective method of lifestyle intervention, and it aims to lower blood pressure and control other risks. Studies have shown that different modes of exercise have varying effects on blood pressure, and individuals with prehypertension or hypertension need to carry out this intervention by using personalized modes of exercise. Methods: We conducted a systematic review and meta-analysis to evaluate the effects of different modes of exercise regimens on systolic blood pressure, diastolic blood pressure and heart rate in individuals with high-normal blood pressure and hypertension. We included 27 trials, and 2731 individuals were under 8 exercise regimens. Stata12.0 statistical software was used for statistical analysis. Results: Heat pools significantly reduced systolic blood pressure (SBP) by 15.62 mmHg (95% confidence interval [CI]: –23.83, –7.41), and cycling reduced SBP by 14.76 mmHg (–17.04, –12.48). Two to three types of aerobic exercise performed at the same time also significantly reduced diastolic blood pressure (DBP) by 5.61 mmHg (–7.71, –3.52), and isometric handgrip training exercise reduced DBP by 5.57 mmHg (–7.48, –3.66). Cycling also significantly reduced heart rate (HR) by 9.57 beats/minute (–11.25, –7.90). Conclusions: The existing literature suggests that different types of exercise can effectively reduce the levels of SBP, DBP and HR in individuals with prehypertension or hypertension.

Skeletal characteristics are important to the growth and development of poultry. In feeding management, constant free feeding (FF) of poultry may lead to imbalance between bone development and weight gain. Feed restriction (FR), to a certain extent, is one way to solve this problem. However, the effect of feed restriction on poultry bone development needs further elucidation at the molecular level. Therefore, in the present study, we investigated the effects of different levels of feed restriction (60% FR, 70% FR, 80% FR, and FF) on the sternum development of ducks at 7 and 8 wk old. In the seventh wk, with increasing feed restriction, the values of traits including body weight, breast muscle weight, sternal weight, keel length, and calcified keel length decreased. However, in the eighth wk, the sternum weight and keel length of ducks treated with 60% FR were unexpectedly higher than those of FF individuals, indicative of catch-up growth. Then, we conducted RNA-seq and metabolomic analysis on sterna from 7- and 8-wk-old FF and 60% FR ducks. The results identified multiple differentially expressed genes (DEGs) associated with sternum development that were influenced by feed restriction. Among them, we found that the mRNA expression levels of the chondroitin sulfate synthase 3 (CHSY3) and annexin A2 (ANXA2) which are involved in glycosaminoglycan biosynthesis and bone mineralization, had smaller changes over time under FR treatment than under FF treatment, implying that the FR treatment to a certain extent prevented the premature calcification and prolonged the development time of duck sternum. In addition, the metabolomic and integrative analyses revealed that several antiaging-related metabolites and genes were associated with sternal catch-up growth. Pyrimidine metabolism was identified as the most significant pathway in which most differential metabolites (DMs) between FF and 60% FR were enriched. The results from integrative analysis revealed that the content and expression of 4-aminobutyric acid (GABA) and its related genes showed relatively higher activity in the 60% FR group than in the FF group. The present study identifies multiple biomarkers associated with duck sternum development that are influenced by feed restriction and suggests the potential mechanism of feed restriction-associated duck sternal catch-up growth.

Bacterial extracellular vesicles (BEVs) have emerged as critical factors involved in gut health regulation, transcending their traditional roles as byproducts of bacterial metabolism. These vesicles function as cargo carriers and contribute to various aspects of intestinal homeostasis, including microbial balance, antimicrobial peptide secretion, physical barrier integrity, and immune system activation. Therefore, any imbalance in BEV production can cause several gut-related issues including intestinal infection, inflammatory bowel disease, metabolic dysregulation, and even cancer. BEVs derived from beneficial or commensal bacteria can act as potent immune regulators and have been implicated in maintaining gut health. They also show promise for future clinical applications in vaccine development and tumor immunotherapy. This review examines the multifaceted role of BEVs in gut health and disease, and also delves into future research directions and potential applications.

The hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-gonadal (HPG) axis plays a central role in mediating physiological responses related to the reproductive system under any stressful condition. However, the molecular mechanism underlying the effects of stress on physiology still needs to be elucidated. This study demonstrated that increasing the stocking density from 4 to 8 birds/m2 during the laying period decreased the egg production rate of laying ducks by 13.04 − 63.55% and feed intake by 7.40 − 23.44%. Transcriptome analysis between high- and low-feeding-density laying ducks revealed 469, 509, 428 and 210 differentially expressed genes (DEGs) in the hypothalamus, pituitary, ovary and follicular membrane, respectively. Gene ontology (GO) and KEGG enrichment analysis showed that the DEGs in the hypothalamus and pituitary were primarily enriched in the biostimulation and dopamine secretion pathways. The major enrichment pathways in the ovarian and follicular membranes involved lipid metabolism, negative regulation of inflammatory response, and steroid hormone biosynthesis. Among the DEGs in the HPG system, POMC and GnRH1 were identified, which may be manifesting their crucial roles in regulating the stress response and reproduction. Our data showed that a high stocking density as environmental stress negatively affects the reproductive performance in ducks through transcriptional changes in the HPG axis.Highlights Raising the stocking density from 4 to 8 birds/m2 decreased the egg production rate and feed intake in laying ducks. The transcriptome indicated that stocking density affects the stress response of laying ducks through the hypothalamus-pituitary. The stress signals are subsequently transmitted to affect gene expression related to the reproduction process in laying ducks’ ovarian and follicular tissues. The hypothalamic expression of POMC and GnRH1 may play a central role in integrating stress signals and the reproductive processes of laying ducks.

Eggs are a major animal protein source for humans. Egg formation is a complex process involved in coordinating various tissues and organs, while blood is necessary for gonad differentiation and egg formation. In this study, non-targeted metabolomics technology was employed to determine the serum metabolites at the time point of 70 days (before laying period, T0), 130 days (pre-laying period, T1), 300 days (peak laying period, T2), and 340 days (post laying period, T3) in female ducks, to provide comprehensive metabolic profiling in reflecting the overall temporal changes. The results showed significant differences in the metabolites of different comparison groups (T0 vs. T1, T2 vs. T3, and T0 & T1 vs. T2& T3), supporting the main physiological responses in ducks are differential among laying periods. L-Aspartic Acid, Biotin, and Thyroxine can be considered the potential biomarkers related to sexual maturity. L-Lysine, Lumichrome, Thiamine, Riboflavin, and Pyridoxine may be biomarkers related to egg formation. Sorbitol, Isorhamnetin, Naringenin, and Hydroxykynurenine were the biomarkers associated with the decline of egg production. In addition, the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis showed that sexual maturity was mainly involved in the biosynthesis of secondary plant metabolites, Tricarboxylic Acid Cycle, Mineral absorption, pentose phosphate pathway, and Oxocarboxylic acid metabolism. Egg formation disturbed amino acid metabolism, vitamin metabolism, and carbohydrate metabolism. The neuroactive ligand-receptor interaction pathway may affect egg production. These findings can detect the different physiological statuses in female ducks and provide a theoretical basis for increasing egg production, and ensuring sustainable farming.Highlights The main physiological responses in ducks are differential among laying periods. 3, 6, and 4 biomarkers related to sexual maturity, the formation of the egg, and the decline of egg production, respectively. Sexual maturity was mainly involved in the biosynthesis of secondary plant metabolites, Tricarboxylic Acid Cycle, Mineral absorption, pentose phosphate pathway, and Oxocarboxylic acid metabolism, and egg formation disturbed amino acid metabolism, vitamin metabolism, and carbohydrate metabolism. while the neuroactive ligand-receptor interaction pathway may affect egg production.

Cigarette smoke exposure is an important factor in chronic inflammation in patients with allergic rhinitis (AR); however, the relationship between cigarette smoke and AR-related glucocorticoid resistance requires further study. In mice, calpeptin significantly reduces inflammation of the lower respiratory tract caused by cigarette smoke, but whether it can treat glucocorticoid-resistant AR caused by cigarette smoke requires further research. In this study, we confirmed that cigarette smoke exposure can aggravate the Th2 inflammatory response in AR leading to glucocorticoid resistance. The underlying mechanism may be related to decreased expression of DNA methyltransferase 3a (Dnmt3a), and increased expression of interferon regulatory factor 1 (IRF1). In addition, we found that calpeptin can inhibit the expression of IRF1 and thus treat AR-associated glucocorticoid resistance in rats exposed to cigarette smoke. These data suggest that calpeptin may downregulate IRF1 and therefore treat glucocorticoid resistance in AR-associated with cigarette smoke exposure.

Fresh onion was used as raw material, sodium hypochlorite cleaning was used as the treatment group, and water cleaning was used as the control group. Stored at 4℃, high-throughput sequencing technology was used to compare the microbial succession and phenotype prediction of fresh-cut onion at the 1st, 3rd and 5th day, and to explore the effects of sodium hypochlorite cleaning on the microflora structure and phenotype of fresh-cut onion during storage. The results showed that at the level of family and genus, sodium hypochlorite cleaning had a significant inhibitory effect on Enterobacteriaceae, Enterobacter, Pantoea and Kosakonia. Compared with the control group, the relative abundance of facultative anaerobic, gramnegative and potential pathogenic phenotypes of bacteria in fresh-cut onion after sodium hypochlorite cleaning decreased, while the relative abundance of aerobic, anaerobic and gram-positive phenotypes increased. After cleaning with sodium hypochlorite, it could to some extent reduce the contamination of pathogenic bacteria in fresh-cut onion, thereby improving the quality and safety of fresh-cut onion.

The Large Hadron Collider (LHC) experiments distribute data by leveraging a diverse array of National Research and Education Networks (NRENs), where experiment data management systems treat networks as a “blackbox” resource. After the High Luminosity upgrade, the Compact Muon Solenoid (CMS) experiment alone will produce roughly 0.5 exabytes of data per year. NREN Networks are a critical part of the success of CMS and other LHC experiments. However, during data movement, NRENs are unaware of data priorities, importance, or need for quality of service, and this poses a challenge for operators to coordinate the movement of data and have predictable data flows across multi-domain networks. The overarching goal of SENSE (The Software-defined network for End-to-end Networked Science at Exascale) is to enable National Labs and universities to request and provision end-to-end intelligent network services for their application workflows leveraging SDN (Software-Defined Networking) capabilities. This work aims to allow LHC Experiments and Rucio, the data management software used by CMS Experiment, to allocate and prioritize certain data transfers over the wide area network. In this paper, we will present the current progress of the integration of SENSE, Multi-domain end-to-end SDN Orchestration with QoS (Quality of Service) capabilities, with Rucio, the data management software used by CMS Experiment.

In the context of achieving the dual-carbon goal, the power sector is actively exploring ways to make a low-carbon transition. The transformation of traditional thermal power involves the safety and reliability of electricity supply in the power system, and the low-carbon transformation involves changes and transformations in various aspects, which requires huge investments and costs. Therefore, it is of great significance to study the low-carbon transition strategy of power grid enterprises and assess the benefits generated by low-carbon transition of power grid enterprises. This paper first analyzes the background and transformation objectives of the low-carbon transformation of the power industry. Then it analyzes the potential of low-carbon development on the power generation side, puts forward the path of low-carbon transformation on the power generation side according to the development potential, and analyzes the role mechanism of low-carbon technology to generate low-carbon benefits, and constructs the assessment model based on system dynamics according to the role mechanism of low-carbon benefits. Simulation analysis is carried out through actual data, and the results show that the low-carbon transition strategy can produce more economic and environmental benefits, and can provide suggestions for subsequent development for reference.

In modern advanced genetics and breeding programs, the study of genes related to pigmentation in ducks is gaining much attention and popularity. Genes and DNA mutation cause variations in the plumage color traits of ducks. Therefore, discovering related genes responsible for different color traits and pigment patterns on each side of the single feathers in Chinese ducks is important for genetic studies. In this study, we collected feather images from 340 ducks and transported them into Image Pro Plus (IPP) 6.0 software to quantify the melanin content in the feathers. Thereafter, a genome-wide association study was conducted to reveal the genes responsible for variations in the feather color trait. The results from this study revealed that the pigmented region was larger in the male ducks as compared to the female ducks. In addition, the pigmented region was larger on the right side of the feather vane than on the left side in both dorsal and ventral feathers, and a positive correlation was observed among the feather color traits. Further, among the annotated genes, WNT3A, DOCK1, RAB1A, and ALDH1A3 were identified to play important roles in the variation in pigmented regions of the various feathers. This study also revealed that five candidate genes, including DPP8, HACD3, INTS14, SLC24A1, and DENND4A, were associated with the color pigment on the dorsal feathers of the ducks. Genes such as PRKG1, SETD6, RALYL, and ZNF704 reportedly play important roles in ventral feather color traits. This study revealed that genes such as WNT3A, DOCK1, RAB1A, and ALDH1A3 were associated with different pigmentation patterns, thereby providing new insights into the genetic mechanisms of single-feather pigmentation patterns in ducks.

Background There were many hypertensive patients at non-high risk of developing COVID-19 that needed to be medical observation at home, but the changes in their blood pressure and measurement frequency as well as heart rate during the period are still unclear. Objective To perform an analysis of the changes in blood pressure and measurement frequency as well as heart rate in hypertensive patients that needed to be medical observation at home. Methods Through the iHealth cloud platform, data〔including age, sex, systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured by the iHealth Clear (BPM1) at home, and heart rate〕were collected from December 1st, 2019 to March 27th, 2020, involving all hypertensive patients in Wuhan who had an ID number for consecutively uploading blood pressure readings, and were desensitized for removing the confidential information. The features of blood pressure during the period were analyzed. ARIMAX model was used to assess the association of age, sex, number of confirmed COVID-19 cases per day, cumulative confirmed COVID-19 deaths, time granularity and the traffic control with participants' blood pressure and hear rates. Results In total, blood pressure readings of 36 472 measurements by the participants using 1 232 iHealth Clear (BPM1) were collected during the 118-day period. Men demonstrated higher mean SBP, DBP and heart rate than women (P

Venous malformation is a common congenital anomaly of vascular development, and endovascular sclerotherapy is currently the first-line treatment for it. Accurate puncture of the lesion is the key to endovascular treatment. Any deviation is likely to result in local ulcers, necrosis and other complications. We described one case, in which a newly developed real-time MRI navigation technology was introduced and sclerotherapy was successfully performed for deep lesions that were difficult to reach by conventional methods. This article reviewed the treatment process of this case, in order to provide guidance and help for venous malformations and other soft tissue diseases in the future.

Aiming at the problem of time-sensitive single target tracking in 3D point cloud, a deep learning algorithm based on deep Hough optimized voting is proposed. Firstly, the algorithm uses PointNet++ network to calculate seed points and extract geometric features from template point cloud and search point cloud. A target-oriented feature extraction method is then used to encode the target information from the template into the search area. Secondly, potential target centers with high confidence are calculated and screened by seed point voting. Finally, multiple proposals are generated through sampling and aggregation of the target center points, and the proposal with the highest score is selected to generate a 3D target box. The algorithm can effectively avoid the time-consuming 3D global search, and is robust to the disorder, irregularity and sparsity of point cloud. In order to verify the effectiveness of the network, experiments are conducted on the public KITTI dataset. Experimental results show that the accuracy of the proposed network is improved by around 10%, compared to the current method based on 3D point clouds. At the same time, the method can run at 43.5 FPS on a single NVIDIA2080S graphics processor.

Highlights 1. ORF3a was successfully transfected into SW480 cells, and its expression was localized in the cytoplasm of SW480 cells. 2. ORF3a inhibited SW480 cell proliferation, invasion and migration, induced their apoptosis, and blocked them in the G1 phase. 3. ORF3a inhibited colorectal tumor growth and accelerated cancer cell death in vivo. 4. Our study provides new insights into the use of viruses in anti-tumor regimens in colorectal cancer.

Abstract As an important monomer for bio-based nylons PA5X, cadaverine is mainly produced by enzymatic decarboxylation of L-lysine. A key issue with this process is the instability of L-lysine decarboxylase (CadA) during the reaction due to the dissociation of CadA subunits with the accumulation of alkaline cadaverine. In this work, we attempted to improve the thermal and alkaline stability of CadA by combining directed evolution and computation-guided virtual screening. Interestingly, site 477 residue located at the protein surface and not the decamer interface was found as a hotspot in directed evolution. By combinatorial mutagenesis of the positive mutations obtained by directed evolution and virtual screening with the previously reported T88S mutation, K477R/E445Q/T88S/F102V was generated as the best mutant, delivering 37% improvement of cadaverine yield at 50 ºC and pH 8.0. Molecular dynamics simulations suggested the improved rigidity of regional structures, increased number of salt bridges, and enhancement of hydrogen bonds at the multimeric interface as possible origins of the improved stability of the mutant. Using this four-point mutant, 160.7 g/L of cadaverine was produced from 2.0 M Lysine hydrochloride at 50 °C without pH regulation, with a conversion of 78.5%, whereas the wild type produced 143.7 g/L cadaverine, corresponding to 70% conversion. This work shows the combination of directed evolution and virtual screening as an efficient protein engineering strategy. Graphical Abstract

Abstract Background Epidemiological evidence between the sleep disorders and allergy-related outcomes is limited. Objectives The purpose of the present study was to estimate the relationship between sleep disorders and allergy-related outcomes in adults. Methods We built logistic regression models to examine the associations between sleep disorders and allergy-related outcomes in adult participants using the 2005–2006 NHANES database. Allergy-related outcomes included sIgE levels, asthma, hay fever, sneezing, wheezing, and eczema. Sleep disorders included sleep latency, sleep length, sleep problems, OSA symptoms, and daytime sleepiness. A t-test was used for between-group comparisons. Results Participants with OSA symptoms had 2.72 × higher odds of experiencing hay fever and 1.54 × higher odds of having eczema compared to Non-OSA symptoms participants. Participants with insufficient sleep (≤ 6 h/night) had 1.27 × higher odds of developing allergic sensitisation compared to participants with adequate sleep (7–8 h/night). Sneezing was positively associated with sleep problems (OR: 1.706; 95% CI 1.386, 2.099), OSA symptoms (OR: 1.297; 95% CI 1.049, 1.605), and daytime sleepiness (OR: 1.569; 95% CI 1.205, 2.04). Conclusion Our findings suggest a positive association between allergy-related outcomes and sleep disorders. In particular, OSA symptoms, daytime sleepiness, and sleep problems are strongly associated with allergic conditions. Graphical Abstract

Overconsumption of high-fat foods increases the risk of fatty liver disease (FLD) and liver cancer with long pathogenic cycles. It is also known that the intake of the chemical poison nitrosamine and its nanopreparations can promote the development of liver injuries, such as FLD, and hepatic fibrosis, and significantly shorten the formation time of the liver cancer cycle. The present work confirmed that the coexposure of a high-fat diet (HFD) and nano-diethylnitrosamine (nano-DEN) altered the tumor microenvironment and studied the effect of this coexposure on the progression of fatty liver malignant transformation into liver cancer. Gene transcriptomics and immunostaining were used to evaluate the tumor promotion effect of the coexposure in mice. After coexposure treatment, tumor nodules were obviously increased, and inflammation levels were elevated. The liver transcriptomics analysis showed that the expression levels of inflammatory, fatty, and fibrosis-related factors in the coexposed group were increased in comparison with the nano-DEN- and high-fat-alone groups. The Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that coexposure aggravated the high expression of genes related to the carcinomatous pathway and accelerated the formation of the tumor microenvironment. The immunohistochemical staining results showed that the coexposure significantly increased the abnormal changes in proteins related to inflammation, proliferation, aging, and hypoxia in mouse liver tissues. The coexposure of high fat and nano-DEN aggravated the process of steatosis and carcinogenesis. In conclusion, the habitual consumption of pickled foods containing nitrosamines in a daily HFD significantly increases the risk of liver pathology lesions progressing from FLD to liver cancer.

Abstract Background Mammalian sex chromosomes provide dosage compensation, but avian lack a global mechanism of dose compensation. Herein, we employed nanopore sequencing to investigate the genetic basis of gene expression and gene dosage effects in avian Z chromosomes at the posttranscriptional level. Results In this study, the gonad and head skin of female and male duck samples (n = 4) were collected at 16 weeks of age for Oxford nanopore sequencing. Our results revealed a dosage effect and local regulation of duck Z chromosome gene expression. Additionally, AS and APA achieve tissue-specific gene expression, and male-biased lncRNA regulates its Z-linked target genes, with a positive regulatory role for gene dosage effects on the duck Z chromosome. In addition, GO enrichment and KEGG pathway analysis showed that the dosage effects of Z-linked genes were mainly associated with the cellular response to hormone stimulus, melanin biosynthetic, metabolic pathways, and melanogenesis, resulting in sex differences. Conclusions Our data suggested that post transcriptional regulation (AS, APA and lncRNA) has a potential impact on the gene expression effects of avian Z chromosomes. Our study provides a new view of gene regulation underlying the dose effects in avian Z chromosomes at the RNA post transcriptional level.

Abstract Though clinical guidelines recommend influenza vaccination for chronic obstructive pulmonary disease (COPD) patients and other high-risk populations, it is unclear whether current vaccination strategies induce optimal antibody responses. This study aimed to identify key variables associated with strain-specific antibody responses in COPD patients and healthy older people. 76 COPD and 72 healthy participants were recruited from two Australian centres and inoculated with influenza vaccine. Serum strain-specific antibody titres were measured pre- and post-inoculation. Seroconversion rate was the primary endpoint. Antibody responses varied between vaccine strains. The highest rates of seroconversion were seen with novel strains (36–55%), with lesser responses to strains included in the vaccine in more than one consecutive year (27–33%). Vaccine responses were similar in COPD patients and healthy participants. Vaccine strain, hypertension and latitude were independent predictors of seroconversion. Our findings reassure that influenza vaccination is equally immunogenic in COPD patients and healthy older people; however, there is room for improvement. There may be a need to personalise the yearly influenza vaccine, including consideration of pre-existing antibody titres, in order to target gaps in individual antibody repertoires and improve protection.

IntroductionCharring process affects the preservation potential of seeds, resulting in limited perceptions of crop assemblages recovered from archaeological layers. Therefore, the specifics of the charring process deserve further investigation. Colloquially referred to as the “Five Grains” (五谷), bread wheat (Triticum aestivum), foxtail millet (Setaria italica), broomcorn millet (Panicum miliaceum), rice (Oryza sativa), and soybean (Glycine max) represent a set of four major cultivated cereals and a pulse constituting crucial staple food in Chinese history and the most frequently discovered crops at archaeological sites in ChinaMethodsThis paper aims to understand the changes in size, volume, and weight loss of grains under variable aerobic charring conditions. The size and weight were measured for the untreated specimens and the specimens heated at different temperatures and over different time-periods.ResultsWe found that temperature and exposure time directly affected the grain size. Specifically, the grains of most species shrank at lower temperatures and expanded rapidly at higher temperatures.DiscussionAmong the “Five Grains”, soybean was the type least affected by charring, followed by wheat, rice, and millet. Volume and weight can be used as conversion factors to minimize the bias in quantitative representation due to varied charring preservation potential. For rice, wheat and soybean, the variation in volume is smaller. For millet, both volume and weight can be used as the control to understand the consequences of charring for the assemblage. Further experiments and comparisons of ancient samples are needed in future studies to investigate other factors that affect the preservation of charred plant remains.

Objective: We aimed to explore a new method to reverse early relapse in patients with AML1-ETO–positive acute myeloid cell transplantation.Methods: A chidamide-based 3-drug combination regimen was used in our center to treat patients with AML1-ETO–positive AML post transplantation but negative flow cytometry results. A retrospective analysis was performed of the survival rate and possible influencing factors of patients with relapse treated with this regimen in our center from January 2018 to January 2022.Results: The overall response rate was 95.8% (23/24), and the median number of treatment courses was 4 (range, 3–12 courses). The total molecular complete response (MCR) was 79.1% (19/24) after all treatments, and the molecular complete response was 37.5% (9/24) after one cycle of treatment but reached 58.3% (14/24) after four cycles; overall, the proportion of MCR increased gradually with the increase in treatment cycles. The projected 5-year overall survival rate was 73.9%. The projected 5-year leukemia-free survival rate was 64.8%, and the projected 1-year cumulative relapse rate was 35.5%. The incidence of grade II–IV graft-versus-host diseases (GVHD) was 29.2% (7/24), and that of grade III–IV GVHD was 20.8% (5/24), which could be effectively controlled by glucocorticoid therapy combined with calcineurin inhibitors The total incidence of chronic GVHD was 29.2% (7/24), and all cases were localized chronic GVHD. The total infection rate was 33.3% (8/24), mainly involving bacterial and fungal infections, and the incidence of life-threatening infections was 4.17% (1/24). The treatment-related mortality rate was 0%; and the total mortality rate was 20.8% (5/24). Nausea and vomiting, thrombocytopenia, and neutropenia were common adverse reactions, all of which were Common Terminology Criteria for Adverse Events grade 2–3 events and reversible after drug withdrawal. In terms of immunity, Th1 cell counts gradually increased, Th17 cell counts gradually decreased, and the Th1/Th17 ratio gradually increased after treatment. The CD8+ T lymphocyte count increased gradually, while the CD4+ T lymphocyte count did not change significantly.Conclusion: Our chidamide-based 3-drug combination regimen led to a high remission rate and tolerable adverse reactions in patients with AML1-ETO–positive post-transplant relapse, and most patients can achieve long-term survival with this regimen.

ABSTRACT: The feather is an important epidermal appendage, plays an important role in the life activities of avian specie, and has important economic value. Revealing the molecular regulation mechanism of feather growth has a significant meaning in studying adaptive evolution, physiology, and mating of avian species and also provides a theoretical reference for poultry breeding. In this study, the genome-wide association analysis (GWAS) of 358 ducks was based on primary feather length phenotypic data (28–60 d), length growth rates (LGRs), and maturity scores (60 d) to explore the genetic basis affecting feather growth and maturation. The results showed that, among the primary feather 1 to 5 in ducks, the mean LGR of primary feather 2 was the fastest, with the longest length. The primary feathers in males grew and matured slightly faster than in females. The mean maturity scores of primary feather 10∼7 were higher than primary feather 1 to 3 in ducks. GWAS further showed 116 SNPs associated with feather length traits. In addition, 2 candidate regions (Chr1: 127,407,230–127,524,879 bp and Chr21: 182,061,707–183,616,298 bp) were associated with LGR, which contain total 13 candidate genes (The extremely significant SNPs were mainly located in 2 genes: Chr1: REPS2 and Chr21: PTPRT). Four candidate regions (Chr1: 29,113,036–28,675,018 bp, Chr2: 18,253,612–149,111,290 bp, Chr15: 6,489,774 to 12,138,221 bp and Chr21: 6,578,021–8,472,904 bp) were associated with feather maturity, which contain total 24 candidate genes (The extremely significant SNPs were mainly located in 4 genes: Chr1: IMMP2L, DOCK4 and DDX10, Chr2: LDLRAD4). In conclusion, sex factors influence feather growth and maturity, and the genetic basis of the growth /maturity trait between different feathers is similar. REPS2, PTPRT genes, and IMMP2L, DOCK4, DDX10, and LDLRAD4 are important candidate genes that influence feather growth and maturity, respectively.

Endothelial-mesenchymal transition (EndMT) is a differentiation process in which endothelial cells lose their own characteristics and acquire mesenchymal-like characteristics, which contributes to the formation and development of atherosclerotic plaques. Until now, there is still a lack of effective measures to treat atherosclerosis (AS), so there is an urgent need to understand the underlying mechanisms of AS. In addition, although various studies have shown that EndMT is involved in the pathological stages of cardiovascular diseases, such as myocardial fibrosis, myocardial hypertrophy, and hypertension, the specific molecular mechanisms driving EndMT are still in the exploratory stage. In this review, we review the role of histone modifications (methylation, demethylation and acetylation, deacetylation) on EndMT in cardiovascular disease, aiming to target histone-modifying enzymes to guide cardiovascular disease therapy.