msBERT-Promoter: a multi-scale ensemble predictor based on BERT pre-trained model for the two-stage prediction of DNA promoters and their strengths.

BACKGROUND: A promoter is a specific sequence in DNA that has transcriptional regulatory functions, playing a role in initiating gene expression. Identifying promoters and their strengths can provide valuable information related to human diseases. In recent years, computational methods have gained prominence as an effective means for identifying promoter, offering a more efficient alternative to labor-intensive biological approaches. RESULTS: In this study, a two-stage integrated predictor called "msBERT-Promoter" is proposed for identifying promoters and predicting their strengths. The model incorporates multi-scale sequence information through a tokenization strategy and fine-tunes the DNABERT model. Soft voting is then used to fuse the multi-scale information, effectively addressing the issue of insufficient DNA sequence information extraction in traditional models. To the best of our knowledge, this is the first time an integrated approach has been used in the DNABERT model for promoter identification and strength prediction. Our model achieves accuracy rates of 96.2% for promoter identification and 79.8% for promoter strength prediction, significantly outperforming existing methods. Furthermore, through attention mechanism analysis, we demonstrate that our model can effectively combine local and global sequence information, enhancing its interpretability. CONCLUSIONS: msBERT-Promoter provides an effective tool that successfully captures sequence-related attributes of DNA promoters and can accurately identify promoters and predict their strengths. This work paves a new path for the application of artificial intelligence in traditional biology.

Cross-and-Diagonal Networks: An Indirect Self-Attention Mechanism for Image Classification.

In recent years, computer vision has witnessed remarkable advancements in image classification, specifically in the domains of fully convolutional neural networks (FCNs) and self-attention mechanisms. Nevertheless, both approaches exhibit certain limitations. FCNs tend to prioritize local information, potentially overlooking crucial global contexts, whereas self-attention mechanisms are computationally intensive despite their adaptability. In order to surmount these challenges, this paper proposes cross-and-diagonal networks (CDNet), innovative network architecture that adeptly captures global information in images while preserving local details in a more computationally efficient manner. CDNet achieves this by establishing long-range relationships between pixels within an image, enabling the indirect acquisition of contextual information. This inventive indirect self-attention mechanism significantly enhances the network's capacity. In CDNet, a new attention mechanism named "cross and diagonal attention" is proposed. This mechanism adopts an indirect approach by integrating two distinct components, cross attention and diagonal attention. By computing attention in different directions, specifically vertical and diagonal, CDNet effectively establishes remote dependencies among pixels, resulting in improved performance in image classification tasks. Experimental results highlight several advantages of CDNet. Firstly, it introduces an indirect self-attention mechanism that can be effortlessly integrated as a module into any convolutional neural network (CNN). Additionally, the computational cost of the self-attention mechanism has been effectively reduced, resulting in improved overall computational efficiency. Lastly, CDNet attains state-of-the-art performance on three benchmark datasets for similar types of image classification networks. In essence, CDNet addresses the constraints of conventional approaches and provides an efficient and effective solution for capturing global context in image classification tasks.

IF1 Promotes Cellular Proliferation and Inhibits Oxidative Phosphorylation in Mouse Embryonic Fibroblasts under Normoxia and Hypoxia.

ATP synthase inhibitory factor subunit 1 (IF1) is an inhibitory subunit of mitochondrial ATP synthase, playing a crucial role in regulating mitochondrial respiration and energetics. It is well-established that IF1 interacts with the F1 sector of ATP synthase to inhibit the reversal rotation and, thus, ATP hydrolysis. Recent evidence supports that IF1 also inhibits forward rotation or the ATP synthesis activity. Adding to the complexity, IF1 may also facilitate mitophagy and cristae formation. The implications of these complex actions of IF1 for cellular function remain obscure. In the present study, we found that IF1 expression was markedly upregulated in hypoxic MEFs relative to normoxic MEFs. We investigate how IF1 affects cellular growth and function in cultured mouse embryonic fibroblasts derived from mouse lines with systemic IF1 overexpression and knockout under normoxia and hypoxia. Cell survival and proliferation analyses revealed that IF1 overexpression exerted limited effects on cellular viability but substantially increased proliferation under normoxia, whereas it facilitated both cellular viability and proliferation under hypoxia. The absence of IF1 may have a pro-survival effect but not a proliferative one in both normoxia and hypoxia. Cellular bioenergetic analyses revealed that IF1 suppressed cellular respiration when subjected to normoxia and was even more pronounced when subjected to hypoxia with increased mitochondrial ATP production. In contrast, IF1 knockout MEFs showed markedly increased cellular respiration under both normoxia and hypoxia with little change in mitochondrial ATP. Glycolytic stress assay revealed that IF1 overexpression modestly increased glycolysis in normoxia and hypoxia. Interestingly, the absence of IF1 in MEFs led to substantial increases in glycolysis. Therefore, we conclude that IF1 mainly inhibits cellular respiration and enhances cellular glycolysis to preserve mitochondrial ATP. On the other hand, IF1 deletion can significantly facilitate cellular respiration and glycolysis without leading to mitochondrial ATP deficit.

Prognosis of infants with congenital pulmonary airway malformations after surgery: a short and mid-term evaluation.

OBJECTIVE: To investigate the postoperative pulmonary function, imaging descriptions and complications in infants with congenital pulmonary airway malformations (CPAM), and to examine the impact of different surgical resections on the prognosis of infants. METHODS: Data of 30 infants with CPAM who underwent surgery at the department of Pediatric Surgery, Guangzhou Women and Children's Medical Center from June 2021 to June 2022 were retrospectively collected and analyzed. The pulmonary function indexes of the infants during the first month and first year after surgery were analyzed to assess prognosis. Pulmonary function data from healthy individuals at similar age were collected as a control group. RESULTS: The post-operative short-term pulmonary function was recovered to a normal level in 26.7% cases of 30 CPAM infants, with a decrease in tidal volume (VT), ratio inspiratory time to expiratory time (TI/TE), time to peak tidal expiratory flow as a proportion of expiratory time (TPTEF/TE), volume to peak expiratory flow as a proportion of exhaled volume (VPEF/VE) and mean expiratory flow as a proportion of mean inspiratory flow (MEF/MIF) when compared to the control group (all P<0.01). One year after operation, 25 CPAM infants received pulmonary function tests and 52% of them had indexes at normal level. There was no statistically significant difference in results of pulmonary function test between infants who received lobectomy and those who received segmentectomy (P>0.05). The postoperative complication rate was 26.7%. CONCLUSION: Over half of CPAM infants have normalized lung function one year after operation and the choice of lobectomy and segmentectomy had no significant difference on prognosis of infants.

Aeromonas veronii tolC modulates its virulence and the immune response of freshwater pearl mussels, Hyriopsis cumingii.

Aeromonas veronii is an opportunistic pathogen that causes diseases in aquatic animals, but its key virulence factors remain unclear. We screened the gene tolC with significantly different expression levels in the two isolates, A. veronii GL2 (higher virulence) and A. veronii FO1 (lower virulence). Therefore, we constructed mutant strain ΔtolC and analyzed its immunological properties. ΔtolC exhibited the reduced ability of biofilms formation, inhibited envelope stress response mediated by several antibiotics except cefuroxime, implying the ability to evade host immunity might be restrained. Challenge tests showed that the LD50 of ΔtolC was 10.89-fold than that of GL2. Enzymatic activities of ΔtolC group were significantly lower and peak time was delayed to 12 h, as demonstrated by qRT-PCR results. Histopathological examination displayed that the degree of tissue damage in ΔtolC group was alleviated. The results show that tolC is an important virulence factor of A. veronii, which provides references for live-attenuated vaccine.

pH-Stimulated Response Gating for Mimic Cytochrome C Transport on Biomimetic Asymmetric Nanochannels.

Proteins are vital components in cells, biological tissues, and organs, playing a pivotal role in growth and developmental processes in living organisms. Cytochrome C (Cyt C) is a class of heme proteins found in almost all life and is involved in cellular energy metabolic processes such as respiration, mainly as electron carriers or terminal reductases. It binds cardiolipin in the inner mitochondrial membrane, leading to apoptosis. It is a challenge to design a simple and effective artificial system to mimic the complex Cyt C biological transport process. In this paper, an asymmetric biomimetic pH-driven protein gate is described by introducing arginine (Arg) at one end of an hourglass-shaped nanochannel. The nanochannel shows a sensitive protonation-driven protein gate that can be "off" at pH = 7 and "on" at pH = 2. Further studies show that differences in the binding of Arg and Cyt C at different levels of protonation lead to different switching behaviors within the nanochannels, which in turn lead to different surface charges within the nanochannels. It can be used for detecting Cyt C and as an excellent and robust gate for developing integrated circuits and nanoelectronic logic devices.

Effects of Valproic Acid Therapy on Rats with Spinal Cord Injury: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematically evaluate the efficacy of valproic acid (VPA) in rats with spinal cord injury (SCI) to reduce the risk of clinical conversion and provide a valuable reference for future animal and clinical studies. METHODS: We searched scientific databases, including PubMed, Ovid-Embase, Web of Science, and Scopus databases. The relevant literature was searched from the establishment date of the database to June 28, 2023. The search results were screened, data were extracted, and the quality of the literature was evaluated independently by 2 reviewers. RESULTS: Among 656 nonduplicated references, 14 articles were included for meta-analysis. The summary results showed that the overall Basso, Beattie and Bresnahan scores of the VPA intervention group were significantly higher than those in the control group at 1-6 weeks after VPA intervention. Subgroup analysis showed that the injury model, administration dose, rat strain, country of study, or follow-up duration had no significant effect on the efficacy of VPA on rats with SCI. In addition, mesh analysis showed that high doses of the VPA group had a better effect on SCI rats, compared with the low dose group and the medium dose group. CONCLUSIONS: To date, this is the first systematic evaluation of the potential effects of VPA on motor recovery in rats with SCI. We concluded that VPA can promote motor recovery in rats with SCI, and higher doses of VPA seem to be more effective in rats with SCI. However, the limited quality and sample of included studies reduced the application of this meta-analysis. In the future, more high-quality, direct comparative studies are needed to explore this issue in depth.

Clinical features and visual prognosis of very late-onset neuromyelitis optica spectrum disorder-related optic neuritis.

BACKGROUND: Very late-onset neuromyelitis optica spectrum disorder-related optic neuritis is limited to a few case reports. OBJECTIVE: To investigate the clinical features and visual prognosis of very late-onset neuromyelitis optica spectrum disorder-related optic neuritis. METHODS: This study evaluated 22 patients with first-onset optic neuritis and fulfilled the 2015 diagnosis criteria for neuromyelitis optica spectrum disorders. RESULTS: The mean age at optic neuritis onset was 73.91 ± 4.71 (range: 70-82) years with a female predominance (81.8%; ratio: 4.5:1). Antinuclear antibody seropositivity and seronegativity were identified in 12 (55.5%) and 10 (45.5%) patients, respectively. Severe visual loss persisted in 19 (19/42, 45.3%) eyes at the last follow-up. Although patients with antinuclear antibody seropositivity had a significantly higher frequency of attacks (P = 0.015), but they had a longer median time to reach severe visual loss (37 vs. 26 months; log-rank test, P = 0.023). Multivariate logistic regression analysis revealed antinuclear antibody seropositivity (hazard ratio = 4.849, 95% confidence interval: 1.309-17.965, P = 0.018) as a good predictor of visual acuity improvement. CONCLUSION: Patients with very late-onset neuromyelitis optica spectrum disorder-related optic neuritis may develop severe optic neuritis, and those with antinuclear antibody seronegativity have a similar clinical presentation but worse outcome than those with seropositivity.

Anisotropic Nonlocal Damping in Ferromagnet/α-GeTe Bilayers Enabled by Splitting Energy Bands.

The understanding and manipulation of anisotropic Gilbert damping is crucial for both fundamental research and versatile engineering and optimization. Although several works on anisotropic damping have been reported, no direct relationship between the band structure and anisotropic damping was established. Here, we observed an anisotropic damping in Fe/GeTe manipulated by the symmetric band structures of GeTe via angle-resolved photoemission spectroscopy. Moreover, the anisotropic damping can be modified by the symmetry of band structures. Our Letter provides insightful understandings of the anisotropic Gilbert damping in ferromagnets interfaced with Rashba semiconductors and suggests the possibility of manipulating the Gilbert damping by band engineering.

Role of contrast-enhanced mammography in the preoperative detection of ductal carcinoma in situ of the breasts: a comparison with low-energy image and magnetic resonance imaging.

OBJECTIVES: To compare contrast-enhanced mammography (CEM) with low-energy image (LEI) alone and with magnetic resonance imaging (MRI) in the preoperative diagnosis of ductal carcinoma in situ (DCIS). METHODS: In this single-center retrospective study, we reviewed 98 pure DCIS lesions in 96 patients who underwent CEM and MRI within 2 weeks preoperatively. The diagnostic performances of each imaging modality, lesion morphology, and extent were evaluated. RESULTS: The sensitivity of CEM to DCIS was similar to that of MRI (92.9% vs. 93.9%, p = 0.77) and was significantly higher than that of LEI alone (76.5%, p = 0.002). The sensitivity of CEM to calcified DCIS (92.4%) was not significantly different from LEI alone (92.4%) and from MRI (93.9%, p = 1.00). However, CEM contributed to the simultaneous comparison of calcifications with enhancements. CEM had considerably higher sensitivity compared with LEI alone (93.8% vs. 43.8%, p < 0.001) and performed similarly to MRI (93.8%, p = 1.00) for noncalcified DCIS. All DCIS lesions were enhanced in MRI, whereas 94.9% (93/98) were enhanced in CEM. Non-mass enhancement was the most common presentation (CEM 63.4% and MRI 66.3%). The difference between the lesion size on each imaging modality and the histopathological size was smallest in MRI, followed by CEM, and largest in LEI. CONCLUSION: CEM was more sensitive than LEI alone and comparable to MRI in DCIS diagnosis. The enhanced morphology of DCIS in CEM was consistent with that in MRI. CEM was superior to LEI alone in size measurement of DCIS. CLINICAL RELEVANCE STATEMENT: This study investigated the value of CEM in the diagnosis and evaluation of DCIS, aiming to offer a reference for the selection of examination methods for DCIS and contribute to the early diagnosis and precise treatment of DCIS. KEY POINTS: • DCIS is an important indication for breast surgery. Early and accurate diagnosis is crucial for DCIS treatment and prognosis. • CEM overcomes the deficiency of mammography in noncalcified DCIS diagnosis, exhibiting similar sensitivity to MRI; and CEM contributes to the comparison of calcification and enhancement of calcified DCIS, thereby outperforming MRI. • CEM is superior to LEI alone and slightly inferior to MRI in the size evaluation of DCIS.

Bootstrapping Elliptic Feynman Integrals Using Schubert Analysis.

The symbol bootstrap has proven to be a powerful tool for calculating polylogarithmic Feynman integrals and scattering amplitudes. In this Letter, we initiate the symbol bootstrap for elliptic Feynman integrals. Concretely, we bootstrap the symbol of the twelve-point two-loop double-box integral in four dimensions, which depends on nine dual-conformal cross ratios. We obtain the symbol alphabet, which contains 100 logarithms as well as nine simple elliptic integrals, via a Schubert-type analysis, which we equally generalize to the elliptic case. In particular, we find a compact, one-line formula for the (2,2) coproduct of the result.

Pathogenicity and inactivated vaccine treatment of Aeromonas veronii JW-4 on crucian carp.

Aeromonas veronii is a common bacterium found in a variety of aquatic environments, capable of causing a diverse array of diseases in both aquatic animals and humans. Therefore, evaluating the pathogenicity of A. veronii and implementing measures to control its spread are essential. In this study, a strain JW-4, identified as A. veronii, was isolated from diseased Scaphesthes macrolepis, a grade Ⅱ protected animal in China. To investigate the pathogenicity of the strain, fish were fed with serial levels JW-4 supplemented diet or basal diet (control group 1, CG1) for 28 days (d). Results showed that JW-4 stimulated an immune response, evidenced by an increase in immune-related enzyme activities (GOT and GPT) of serum and liver and an upregulation of genes expression levels (TNF-α and IFN-γ) of liver and spleen, and these effects gradually decreased over time. Histopathological examination revealed that JW-4 could alter the tissue structure of immune organs, such as liver and kidney. These changes were accompanied by vacuolar degeneration, nuclear dissolution, and an increased lymphocyte count. To assess protective effects of a vaccine against this strain, fish were injected with an inactivated vaccine (immunization group, IG) or 0.85% sterile saline (control group 2, CG2) for 28-day observation period, then challenged with JW-4 on the 28th day. The inactivated vaccine enhanced total and specific IgM to A. veronii levels of the fish, resulting in a relative percentage survival of 75% in IG. These findings provide a foundation for identifying pathogenic bacteria and developing more effective prophylactic strategies in aquaculture.

Evaluation of toxicity and biocompatibility of a novel Mg-Nd-Gd-Sr alloy in the osteoblastic cell.

BACKGROUND: We investigated the toxicity and biocompatibility of a novel Mg-3Nd-1Gd-0.3Sr-0.2Zn-0.4Zr (abbreviated to Mg-Nd-Gd-Sr) alloy in the osteoblastic cell line MC3T3-E1 as osteoblasts play an important role in bone repair and remodeling. METHODS: We used cytotoxicity tests and apoptosis to investigate the effects of the Mg-Nd-Gd-Sr alloy on osteoblastic cells. Cell bioactivity, cell adhesion, cell proliferation, mineralization, ALP activity, and expression of BMP-2 and OPG by osteoblastic cells were also used to investigate the biocompatibility of Mg-Nd-Gd-Sr alloy. RESULTS: The results showed that the Mg-Nd-Gd-Sr alloy had no obvious cytotoxicity, and did not induce apoptosis to MC3T3-E1 cells. Compared with the control group, the number of adherent cells within 12 h was increased significantly in each experimental group (P < 0.05); the OD value of MC3T3-E1 cells was increased significantly in each experimental group on days 1 and 3 of culture (P < 0.05); the number of mineralized nodules formed in each experimental group was significantly increased (P < 0.05), and ALP activity was significantly increased in each experimental group (P < 0.05). RT-PCR results showed that the mRNA expression of BMP-2 and OPG was significantly higher in each experimental group compared with the control group (P < 0.05). Western blotting showed that the Mg-Nd-Gd-Sr alloy extract significantly increased the protein expression of BMP-2 and OPG compared with the control group (P < 0.05). CONCLUSIONS: Our data indicated that the novel Mg-Nd-Gd-Sr-Zn-Zr alloy had no obvious cytotoxic effects, and did not cause apoptosis to MC3T3-E1 cells; meanwhile it promoted cell adhesion, cell proliferation, mineralization, and ALP activity of osteoblasts. During this process, there was an increase in the expressions of BMP-2 and OPG mRNAs and proteins.

Association of choline and betaine with the risk of cardiovascular disease and all-cause mortality: Meta-analysis.

BACKGROUND: This study aimed to systematically evaluate the role of circulating levels of choline and betaine in the risk of cardiovascular disease (CVD) and all-cause mortality by comprehensively reviewing observational studies. METHODS: This study was conducted according to PRISMA 2020 statement. Six electronic databases, including PubMed, Embase and China National Knowledge Infrastructure (CNKI), were searched for cohort studies and derivative research design types (nested case-control and case-cohort studies) from the date of inception to March 2022. We pooled relative risk (RR) and 95% confidence interval (CI) of the highest versus lowest category and per SD of circulating choline and betaine concentrations in relation to the risk of CVD and all-cause mortality. RESULTS: In the meta-analysis, 17 studies with a total of 33,009 participants were included. Random-effects model results showed that highest versus lowest quantile of circulating choline concentrations were associated with the risk of CVD (RR = 1.29, 95% CI: 1.04-1.61) and all-cause mortality (RR = 1.62, 95% CI: 1.12-2.36). We also observed the risk of CVD were increased 13% (5%-22%) with per SD increment. Furthermore, highest versus lowest quantile of circulating betaine concentrations were not associated with the risk of CVD (RR = 1.07, 95% CI: 0.92-1.24) and all-cause mortality (RR = 1.39, 95% CI: 0.96-2.01). However, the risk of CVD was increased 14% (5%-23%) with per SD increment. CONCLUSIONS: Higher levels of circulating choline were associated with a higher risk of CVD and all-cause mortality.

Efficient methods for multiple types of precise gene-editing in Chlamydomonas.

Precise gene-editing using CRISPR/Cas9 technology remains a long-standing challenge, especially for genes with low expression and no selectable phenotypes in Chlamydomonas reinhardtii, a classic model for photosynthesis and cilia research. Here, we developed a multi-type and precise genetic manipulation method in which a DNA break was generated by Cas9 nuclease and the repair was mediated using a homologous DNA template. The efficacy of this method was demonstrated for several types of gene editing, including inactivation of two low-expression genes (CrTET1 and CrKU80), the introduction of a FLAG-HA epitope tag into VIPP1, IFT46, CrTET1 and CrKU80 genes, and placing a YFP tag into VIPP1 and IFT46 for live-cell imaging. We also successfully performed a single amino acid substitution for the FLA3, FLA10 and FTSY genes, and documented the attainment of the anticipated phenotypes. Lastly, we demonstrated that precise fragment deletion from the 3'-UTR of MAA7 and VIPP1 resulted in a stable knock-down effect. Overall, our study has established efficient methods for multiple types of precise gene editing in Chlamydomonas, enabling substitution, insertion and deletion at the base resolution, thus improving the potential of this alga in both basic research and industrial applications.

Prevalence and correlators of burnout among health professionals during different stages of the COVID-19 pandemic in China.

Background: Persistently increased workload and stress occurred in health professionals (HPs) during the past 3 years as the COVID-19 pandemic continued. The current study seeks to explore the prevalence of and correlators of HPs' burnout during different stages of the pandemic. Methods: Three repeated online studies were conducted in different stages of the COVID-19 pandemic: wave 1: after the first peak of the pandemic, wave 2: the early period of the zero-COVID policy, and wave 3: the second peak of the pandemic in China. Two dimensions of burnout, emotional exhaustion (EE) and declined personal accomplishment (DPA), were assessed using Human Services Survey for Medical Personnel (MBI-HSMP), a 9-item Patient Health Questionnaire (PHQ-9), and a 7-item Generalized Anxiety Disorder (GAD-7) to assess mental health conditions. An unconditional logistic regression model was employed to discern the correlators. Results: There was an overall prevalence of depression (34.9%), anxiety (22.5%), EE (44.6%), and DPA (36.5%) in the participants; the highest prevalence of EE and DPA was discovered in the first wave (47.4% and 36.5%, respectively), then the second wave (44.9% and 34.0%), and the third wave had the lowest prevalence of 42.3% and 32.2%. Depressive symptoms and anxiety were persistently correlated with a higher prevalence risk of both EE and DPA. Workplace violence led to a higher prevalence risk of EE (wave 1: OR = 1.37, 95% CI: 1.16-1.63), and women (wave 1: OR = 1.19, 95% CI: 1.00-1.42; wave 3: OR =1.20, 95% CI:1.01-1.44) and those living in a central area (wave 2: OR = 1.66, 95% CI: 1.20-2.31) or west area (wave 2: OR = 1.54, 95% CI: 1.26-1.87) also had a higher prevalence risk of EE. In contrast, those over 50 years of age (wave 1: OR = 0.61, 95% CI: 0.39-0.96; wave 3: OR = 0.60, 95% CI: 0.38-0.95) and who provided care to patients with COVID-19 (wave 2: OR = 0.73, 95% CI: 0.57-0.92) had a lower risk of EE. Working in the psychiatry section (wave 1: OR = 1.38, 95% CI: 1.01-1.89) and being minorities (wave 2: OR = 1.28, 95% CI: 1.04-1.58) had a higher risk of DPA, while those over 50 years of age had a lower risk of DPA (wave 3: OR = 0.56, 95% CI: 0.36-0.88). Conclusion: This three-wave cross-sectional study revealed that the prevalence of burnout among health professionals was at a high level persistently during the different stages of the pandemic. The results suggest that functional impairment prevention resources and programs may be inadequate and, as such, continuous monitoring of these variables could provide evidence for developing optimal strategies for saving human resources in the coming post-pandemic era.

Association of polymorphisms of calcium reabsorption genes SLC12A1, KCNJ1 and SLC8A1 with colorectal adenoma.

BACKGROUND: In recent years, morbidity and mortality from colorectal cancer have increased. Colorectal adenoma is the main precancerous lesion. Understanding the pathogenesis of colorectal adenoma will help to improve the early diagnosis rate of colorectal cancer. METHODS: In this case-control study, we focused on three single nucleotide polymorphisms (SNPs) in genes SLC8A1 (rs4952490), KCNJ1 (rs2855798), and SLC12A1 (rs1531916). We analyzed 207 colorectal adenoma patients (112 high-risk cases and 95 low-risk cases) and 212 control subjects by Sanger sequencing. A food frequency questionnaire (FFQ) was used to survey demographic characteristics and dietary nutrition. RESULTS: In the overall analysis, the results suggested that the AA+AG and AG genotype carriers of rs4952490 had a 73.1% and 78% lower risk of colorectal adenoma compared to GG genotype carriers, respectively. However rs2855798 and rs1531916 were not associated with the incidence of colorectal adenoma. Additionally, stratified analysis showed that rs4952490 AA+AG and AG genotypes had a protective effect against low-risk colorectal adenoma in patients aged ≤ 60 years old who were non-smokers. We also observed that when calcium intake was higher than 616 mg/d and patients carried at least one gene with variant alleles there was a protective effect against low-risk colorectal adenoma. CONCLUSIONS: Interactions between dietary calcium intake and calcium reabsorption genes may affect the occurrence and development of colorectal adenoma.

Comparison of the effect of quercetin and daidzein on production performance, anti-oxidation, hormones, and cecal microflora in laying hens during the late laying period.

This study aims to compare the effect of quercetin and daidzein on production performance, anti-oxidation, hormones, and cecal microflora in laying hens during the late laying period. A total of 360 53-week-old healthy Hyline brown laying hens were randomly divided into 3 groups (control, 0.05% quercetin, and 0.003% daidzein). Diets were fed for 10 wk, afterwards 1 bird per replicate (6 replicates) were euthanized for sampling blood, liver and cecal digesta. Compared with the control, quercetin significantly increased laying rate and decreased feed-to-egg weight ratio from wk 1 to 4, wk 5 to 10, and wk 1 to 10 (P < 0.05). Quercetin significantly increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased catalase (CAT) activity and malondialdehyde (MDA) content in serum and liver (P < 0.05) and increased content of total antioxidant capacity (T-AOC) in liver (P < 0.05). Quercetin increased content of estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), insulin-like growth factor 1 (IGF-1), triiodothyronine (T3) and thyroxine (T4) in serum (P < 0.05). Quercetin significantly decreased the relative abundance of Bacteroidaceae and Bacteroides (P < 0.01) and significantly increased the relative abundance of Lactobacillaceae and Lactobacillus (P < 0.05) at family and genus levels in cecum. Daidzein did not significantly influence production performance from wk 1 to 10. Daidzein significantly increased SOD activity and decreased CAT activity and MDA content in serum and liver (P < 0.05), and increased T-AOC content in liver (P < 0.05). Daidzein increased content of FSH, IGF-1, T3 in serum (P < 0.05). Daidzein increased the relative abundance of Rikenellaceae RC9 gut group at genus level in cecum (P < 0.05). Quercetin increased economic efficiency by 137.59% and 8.77%, respectively, compared with daidzein and control. In conclusion, quercetin improved production performance through enhancing antioxidant state, hormone levels, and regulating cecal microflora in laying hens during the late laying period. Quercetin was more effective than daidzein in improving economic efficiency.

Real-Time Visualization of Cytosolic and Mitochondrial ATP Dynamics in Response to Metabolic Stress in Cultured Cells.

Adenosine 5' triphosphate (ATP) is the energy currency of life, which is produced in mitochondria (~90%) and cytosol (less than 10%). Real-time effects of metabolic changes on cellular ATP dynamics remain indeterminate. Here we report the design and validation of a genetically encoded fluorescent ATP indicator that allows for real-time, simultaneous visualization of cytosolic and mitochondrial ATP in cultured cells. This dual-ATP indicator, called smacATPi (simultaneous mitochondrial and cytosolic ATP indicator), combines previously described individual cytosolic and mitochondrial ATP indicators. The use of smacATPi can help answer biological questions regarding ATP contents and dynamics in living cells. As expected, 2-deoxyglucose (2-DG, a glycolytic inhibitor) led to substantially decreased cytosolic ATP, and oligomycin (a complex V inhibitor) markedly decreased mitochondrial ATP in cultured HEK293T cells transfected with smacATPi. With the use of smacATPi, we can also observe that 2-DG treatment modestly attenuates mitochondrial ATP and oligomycin reduces cytosolic ATP, indicating the subsequent changes of compartmental ATP. To evaluate the role of ATP/ADP carrier (AAC) in ATP trafficking, we treated HEK293T cells with an AAC inhibitor, Atractyloside (ATR). ATR treatment attenuated cytosolic and mitochondrial ATP in normoxia, suggesting AAC inhibition reduces ADP import from the cytosol to mitochondria and ATP export from mitochondria to cytosol. In HEK293T cells subjected to hypoxia, ATR treatment increased mitochondrial ATP along with decreased cytosolic ATP, implicating that ACC inhibition during hypoxia sustains mitochondrial ATP but may not inhibit the reversed ATP import from the cytosol. Furthermore, both mitochondrial and cytosolic signals decrease when ATR is given in conjunction with 2-DG in hypoxia. Thus, real-time visualization of spatiotemporal ATP dynamics using smacATPi provides novel insights into how cytosolic and mitochondrial ATP signals respond to metabolic changes, providing a better understanding of cellular metabolism in health and disease.