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Abstract. Background:. Non-alcoholic fatty liver disease (NAFLD) and inflammatory bowel disease (IBD) have shown similar worsening epidemic patterns globally and shared various overlapping pathophysiological mechanisms. However, evidence on the relationship between NAFLD and IBD risk is lacking. We aimed to investigate the associations between long-term risk of incident IBD and NAFLD in a large prospective cohort. Methods:. Participants from the United Kingdom Biobank cohort (https://biobank.ndph.ox.ac.uk/) who were free of IBD and alcoholic liver disease at baseline were enrolled. Baseline non-alcoholic fatty liver degree was measured by the well-established fatty liver index (FLI). The outcomes of interest included incident IBD, ulcerative colitis (UC), and Crohn's disease (CD). Multivariable Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results:. Among 418,721 participants (mean FLI: 48.11 ± 30.11), 160,807 (38.40%) participants were diagnosed as NAFLD at baseline. During a median of 12.4 years' follow-up, 2346 incident IBD cases (1545 UC, 653 CD, and 148 IBD-unclassified) were identified. Due to limited events, those IBD-unclassified were combined in UC or CD when examining the associated risk of UC or CD, separately. Compared with the lowest quartile of FLI, the highest quartile showed a separately 36.00%, 25.00%, and 58.00% higher risk of incident IBD (HRQ4 vs. Q1 = 1.36, 95% CI: 1.19–1.55, Ptrend

Abstract The platelet/high-density lipoprotein ratio (PHR) has been identified as a significant indicator of inflammation and a hypercoagulable state, demonstrating a strong link with the severity of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS). However, its correlation with hyperuricemia has not yet been documented. This study utilized a cross-sectional design, analyzing data collected from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016 in the United States. The platelet/high-density lipoprotein ratio (PHR) was determined by dividing the number of platelets (PLT) by the level of high-density lipoprotein cholesterol (HDL-C). We employed multivariable logistic regression analyses, generalized additive models, and subgroup analyses to investigate the correlation between PHR and hyperuricemia. The study revealed a hyperuricemia prevalence of 18.56%. Analysis indicated a significant positive correlation between PHR and the risk of hyperuricemia (OR 1.11, 95% CI 1.08, 1.14). This correlation remained consistent across different subgroups including age, ethnicity, gender, and body mass index (BMI). Smooth curve fitting demonstrated a saturation effect between PHR and the risk of hyperuricemia. PHR is positively correlated with hyperuricemia and may serve as a novel biomarker for predicting the onset of this condition. Additionally, targeted interventions to improve PHR might help reduce the incidence of hyperuricemia.

Objective: Circulating tumor DNA (ctDNA) is increasingly being used as a potential prognostic biomarker in cancer patients. We aimed to assess the prognostic value of ctDNA in different subtypes of breast cancer patients throughout the whole treatment cycle. Materials and methods: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov databases were searched from January 2016 to May 2022. The following search terms were used: ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma. Only studies written in English were included. The following pre-specified criteria should be met for inclusion: (i) original articles, conference abstracts, etc.; (ii) patients with breast cancer; (iii) ctDNA measurement; and (iv) clinical outcome data such as recurrence-free survival (RFS) and overall survival (OS). The random-effects model was preferred considering the potential heterogeneity across studies. The main outcomes are ctDNA detection rate and postoperative long-term outcomes (RFS and OS). Results: A total of 24 studies were screened. At every measurement time, the ctDNA detection rate of the HR+ subgroup was similar to that of the HR- subgroup (P = 0.075; P = 0.458; P = 0.744; and P = 0.578), and the ctDNA detection rate of the HER2+ subgroup was similar to that of the HER2- subgroup (P = 0.805; P = 0.271; P = 0.807; and P = 0.703). In the HR+ subgroup, RFS and OS of ctDNA positive patients were similar to those of ctDNA negative patients (P = 0.589 and P = 0.110), while RFS and OS of the ctDNA positive group was significantly shorter than those of the ctDNA negative patients in the HR- subgroup (HR = 4.03, P < 0.001; HR = 3.21, P < 0.001). According to HER grouping, the results were the same as above. In the triple negative breast cancer (TNBC) subgroup, the RFS and OS of ctDNA-positive patients was significantly shorter than of the ctDNA negative patients before and after surgery. Conclusions: ctDNA was more predictive of recurrence-free survival and overall survival in the HR- subgroup than in the HR+ subgroup, and the same result was showed in the HER2- subgroup vs. HER2+ subgroup. The prognosis of the TNBC subtype is closely related to ctDNA before and after surgery.

Abstract To solve the difficulties in threshold selection and poor performance under low signal‐to‐noise ratio (SNR) conditions in existing spectrum sensing algorithms, a graph‐based spectrum sensing algorithm using nonlinear function regulation was proposed. The idea was to add a specific nonlinear transformation between the normalisation and quantization steps of the existing signal‐to‐graph converter (SGC). If the autocorrelation function of the observed signal selected as the input fed to SGC, the nonlinear function has the ability to adjust the uniformity of its probability distribution, increasing the probability of the observed signal being transformed into a complete graph under the alternative hypothesis, whereas remaining a noncomplete graph under the null hypothesis. Thus transformed the graph‐based spectrum sensing into a complete graph‐detection problem. Based on the theory of dispersive ordering, a theoretical analysis of the mechanism by which nonlinear transformations affect graph connectivity was conducted. The simulation results showed that the detection performance of the proposed algorithm was superior to that of existing graph‐based spectrum sensing algorithms. When SNR was −7 dB, the detection probability of the proposed algorithm exceeded 95%. Moreover, among the existing graph‐based spectrum sensing algorithms, the proposed algorithm exhibited the lowest computational complexity apart from the block range‐based method.

Abstract Composed of obesity and lipid parameters, the cardiometabolic index (CMI) has emerged as a novel diagnostic tool. Originally developed for diabetes diagnosis, its application has expanded to identifying patients with cardiovascular diseases, such as atherosclerosis and hypertension. However, the relationship between CMI and non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in the US population remains unclear. This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning 2017–2020, involving 2996 participants aged 20 years or older. Vibration controlled transient elastography using a FibroScan® system (model 502, V2 Touch) with controlled attenuation parameter measurements identified NAFLD at a threshold of ≥ 274 dB/m, while liver stiffness measurement (LSM) results (median, ≥ 8.2 kPa) indicated fibrosis. A multifactorial logistic regression model explored the relationship between CMI and NAFLD and fibrosis. The effectiveness of CMI in detecting NAFLD and liver fibrosis was assessed through receiver operating characteristic curve analysis. Controlling for potential confounders, CMI showed a significant positive association with NAFLD (adjusted OR = 1.44, 95% CI 1.44–1.45) and liver fibrosis (adjusted OR = 1.84, 95% CI 1.84–1.85). The Areas Under the Curve for predicting NAFLD and fibrosis were 0.762 (95% CI 0.745 ~ 0.779) and 0.664(95% CI 0.633 ~ 0.696), respectively, with optimal cut-off values of 0.462 and 0.527. There is a positive correlation between CMI and NAFLD and fibrosis, which is a suitable and simple predictor of NAFLD and fibrosis.

Objective: To establish the common mode of HPLC fingerprints of Wu and Hong Tianma in different regions of Guizhou, and to determine the contents of 8 chemical components in Wu and Hong Tianma in different regions of Guizhou, and to preliminarily analyze the quality differences of chemical components in Wu and Hong Tianma in different regions of Guizhou. Method: HPLC method was used with Waters-C18 (4.6×250 mm; 5 μm) with octadecylsilane bonded silica gel as filler, 0.1 % formic acid as mobile phase A, acetonitrile as mobile phase B, flow rate 1 mL/min, the column temperature was 30 ℃, the wavelength was 270 nm, and the gradient elution was used to establish the common mode of fingerprints of 15 batches of Wu Tianma and 10 batches of Hong Tianma. Cluster analysis, principal component analysis, orthogonal partial least squares-discriminant analysis, Person correlation analysis and other multivariate statistical analysis methods were used to determine whether there were differences in the content of chemical components of Wu Tianma and Hong Tianma in different regions of Guizhou. The contents of adenosine, gastrodin, p-hydroxybenzyl alcohol, parishin E, p-hydroxybenzaldehyde, parishin B, parishin C and parishin A were determined. Results: The similarity of 15 batches of Wu Tianma was 0.868~0.986, and the similarity of 10 batches of Hong Tianma was 0.919~0.990. A total of 15 common peaks were calibrated and 8 common peaks were identified. According to cluster analysis, principal component analysis and orthogonal partial least squares-discriminant analysis, Wu and Hong Tianma in different regions of Guizhou had obvious regional differences and the different chemical components of Tianma in different regions were adenosine, gastrodin, p-hydroxybenzyl alcohol, parishin E, parishin B and parishin A. The results of chemical components determination and Person correlation analysis showed that there was a correlation between the production areas and the contents of gastrodin, parishin C and parishin A, and there was a correlation between the different varieties of Wu Tianma and Hong Tianma and the contents of adenosine, gastrodin and parishin C. Conclusion: Wu Tianma and Hong Tianma in different regions of Guizhou have regional differences as well as variety differences. The contents of adenosine, gastrodin, p-hydroxybenzyl alcohol, parishin E, parishin B, parishin C and parishin A may be the quality difference components of Tianma in different regions of Guizhou. The contents of adenosine, gastrodin and parishin C are the quality difference components of different varieties of Wu Tianma and Hong Tianma in Guizhou. The quality analysis method is simple, stable and reliable, which can provide theoretical reference for further quality evaluation of Wu and Hong Tianma in different regions of Guizhou.

Abstract Lysine crotonylation (Kcr) is a recently discovered histone acylation modification that is closely associated with gene expression, cell proliferation, and the maintenance of stem cell pluripotency and indicates the transcriptional activity of genes and the regulation of various biological processes. During cell culture, the introduction of exogenous croconic acid disodium salt (Nacr) has been shown to modulate intracellular Kcr levels. Although research on Kcr has increased, its role in cell growth and proliferation and its potential regulatory mechanisms remain unclear compared to those of histone methylation and acetylation. Our investigation demonstrated that the addition of 5 mM Nacr to cultured bovine fibroblasts increased the expression of genes associated with Kcr modification, ultimately promoting cell growth and stimulating cell proliferation. Somatic cell nuclear transfer of donor cells cultured in 5 mM Nacr resulted in 38.1% blastocyst development, which was significantly greater than that in the control group (25.2%). This research is important for elucidating the crotonylation modification mechanism in fibroblast proliferation to promote the efficacy of somatic cell nuclear transfer.

Marine summer fishing moratorium is one of the most important fishery conservation policies in China at present, which is constantly adjusted and improved in practice. It plays an important role in improving the marine fishery ecology and promoting the sustainable development of fishery. In order to demonstrate the implementation effect of the policy, this paper first reviewed the history and characteristics of the change of the policy, and then took the East China Sea as an example to analyze the changes of fishing output, fishing effort and fishing efficiency in the East China Sea since the implementation of the policy, and discussed the changes of the output and quality of the representative catches. Based on the investigation of the catch of some fishing ports in the south of the East China Sea, this paper analyzed the existing problems of the current summer fishing moratorium, and then put forward some measures and suggestions for further optimization.

The study aims to characterize the immune cell landscape in convalescent Asian seabass (Lates calcarifer) blood samples after exposure to scale-drop disease virus (SDDV). Traditional immunophenotyping approaches used in human and mouse studies are impractical for non-model organisms like the Asian seabass due to the lack of specific antibody-based reagents. To overcome this challenge, 10x Genomics single-cell RNA sequencing was employed. The analysis of blood samples revealed 24 distinct leukocyte clusters, with elevated proportions of B cells, granulocytes, and T cells in the convalescent group compared to the uninfected group. While distinguishing granulocyte and macrophage subsets was challenging, the analysis of differential gene expression in the macrophage population indicated that the upregulated genes were linked to inflammatory processes. Specific T cell clusters showed notable expressions of cd4-1, cd8a, perforin-1 and il-2rβ, suggesting the presence of CD4+ T helper (Th), CD8+ cytotoxic T (Tc) cells, immature T cells, and naive T cells. Attempts to categorize CD4+ T cells into Th subtypes lacked clear distinctions, while CD8+ T cells exhibited three clusters, predominantly Tc1 cells. Furthermore, comparisons between convalescent and uninfected groups revealed increased percentages of activated and antibody-secreting B cells in the convalescent group. This single-cell analysis provides vital insights into the immune cell dynamics in convalescent and uninfected Asian seabass, providing valuable information on potential immune responses to SDDV infection.

Abstract Background SH3 and multiple ankyrin repeat domains protein 3 (SHANK3) monogenic mutations or deficiency leads to excessive stereotypic behavior and impaired sociability, which frequently occur in autism cases. To date, the underlying mechanisms by which Shank3 mutation or deletion causes autism and the part of the brain in which Shank3 mutation leads to the autistic phenotypes are understudied. The hypothalamus is associated with stereotypic behavior and sociability. p38α, a mediator of inflammatory responses in the brain, has been postulated as a potential gene for certain cases of autism occurrence. However, it is unclear whether hypothalamus and p38α are involved in the development of autism caused by Shank3 mutations or deficiency. Methods Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and immunoblotting were used to assess alternated signaling pathways in the hypothalamus of Shank3 knockout (Shank3 −/− ) mice. Home-Cage real-time monitoring test was performed to record stereotypic behavior and three-chamber test was used to monitor the sociability of mice. Adeno-associated viruses 9 (AAV9) were used to express p38α in the arcuate nucleus (ARC) or agouti-related peptide (AgRP) neurons. D176A and F327S mutations expressed constitutively active p38α. T180A and Y182F mutations expressed inactive p38α. Results We found that Shank3 controls stereotypic behavior and sociability by regulating p38α activity in AgRP neurons. Phosphorylated p38 level in hypothalamus is significantly enhanced in Shank3 −/− mice. Consistently, overexpression of p38α in ARC or AgRP neurons elicits excessive stereotypic behavior and impairs sociability in wild-type (WT) mice. Notably, activated p38α in AgRP neurons increases stereotypic behavior and impairs sociability. Conversely, inactivated p38α in AgRP neurons significantly ameliorates autistic behaviors of Shank3 −/− mice. In contrast, activated p38α in pro-opiomelanocortin (POMC) neurons does not affect stereotypic behavior and sociability in mice. Limitations We demonstrated that SHANK3 regulates the phosphorylated p38 level in the hypothalamus and inactivated p38α in AgRP neurons significantly ameliorates autistic behaviors of Shank3 −/− mice. However, we did not clarify the biochemical mechanism of SHANK3 inhibiting p38α in AgRP neurons. Conclusions These results demonstrate that the Shank3 deficiency caused autistic-like behaviors by activating p38α signaling in AgRP neurons, suggesting that p38α signaling in AgRP neurons is a potential therapeutic target for Shank3 mutant-related autism.

Objective: Circulating tumor DNA (ctDNA) is increasingly being used as a potential prognosis biomarker in patients of breast cancer. This review aims to assess the clinical value of ctDNA in outcome prediction in breast cancer patients throughout the whole treatment cycle. Methods: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov were searched from January 2016 to May 2022. Conference abstracts published in last three years were also included. The following search terms were used: ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma. Only studies written in English languages were included. The following pre-specified criteria should be met for inclusion: (1) observational studies (prospective or retrospective), randomized control trials, case-control studies and case series studies; (2) patients with breast cancer; (3) ctDNA measurement; (4) clinical outcome data such as objective response rate (ORR), pathological complete response (pCR), relapse-free survival (RFS), overall survival (OS), and so on. The random-effect model was preferred considering the potential heterogeneity across studies. The primary outcomes included postoperative short-term outcomes (ORR and pCR) and postoperative long-term outcomes (RFS, OS, and relapse). Secondary outcomes focused on ctDNA detection rate. Results: A total of 30 studies, comprising of 19 cohort studies, 2 case-control studies and 9 case series studies were included. The baseline ctDNA was significantly negatively associated with ORR outcome (Relative Risk [RR] = 0.65, 95% confidence interval [CI]: 0.50–0.83), with lower ORR in the ctDNA-positive group than ctDNA-negative group. ctDNA during neoadjuvant therapy (NAT) treatment was significantly associated with pCR outcomes (Odds Ratio [OR] = 0.15, 95% CI: 0.04–0.54). The strong association between ctDNA and RFS or relapse outcome was significant across the whole treatment period, especially after the surgery (RFS: Hazard Ratio [HR] = 6.74, 95% CI: 3.73–12.17; relapse outcome: RR = 7.11, 95% CI: 3.05–16.53), although there was heterogeneity in these results. Pre-operative and post-operative ctDNA measurements were significantly associated with OS outcomes (pre-operative: HR = 2.03, 95% CI: 1.12–3.70; post-operative: HR = 6.03, 95% CI: 1.31–27.78). Conclusions: In this review, ctDNA measurements at different timepoints are correlated with evaluation indexes at different periods after treatment. The ctDNA can be used as an early potential postoperative prognosis biomarker in breast cancer, and also as a reference index to evaluate the therapeutic effect at different stages.

Agranulocytosis, induced by non-chemotherapy drugs, is a serious medical condition that presents a formidable challenge in predictive toxicology due to its idiosyncratic nature and complex mechanisms. In this study, we assembled a dataset of 759 compounds and applied a rigorous feature selection process prior to employing ensemble machine learning classifiers to forecast non-chemotherapy drug-induced agranulocytosis (NCDIA) toxicity. The balanced bagging classifier combined with a gradient boosting decision tree (BBC + GBDT), utilizing the combined descriptor set of DS and RDKit comprising 237 features, emerged as the top-performing model, with an external validation AUC of 0.9164, ACC of 83.55%, and MCC of 0.6095. The model’s predictive reliability was further substantiated by an applicability domain analysis. Feature importance, assessed through permutation importance within the BBC + GBDT model, highlighted key molecular properties that significantly influence NCDIA toxicity. Additionally, 16 structural alerts identified by SARpy software further revealed potential molecular signatures associated with toxicity, enriching our understanding of the underlying mechanisms. We also applied the constructed models to assess the NCDIA toxicity of novel drugs approved by FDA. This study advances predictive toxicology by providing a framework to assess and mitigate agranulocytosis risks, ensuring the safety of pharmaceutical development and facilitating post-market surveillance of new drugs.

Abstract Human stem cells and derivatives transplantation are widely used to treat nervous system diseases, while the fate determination of transplanted cells is not well elucidated. To explore cell fate changes of human brain organoids before and after transplantation, human brain organoids are transplanted into prefrontal cortex (PFC) and hippocampus (HIP), respectively. Single‐cell sequencing is then performed. According to time‐series sample comparison, transplanted cells mainly undergo neural development at 2 months post‐transplantation (MPT) and then glial development at 4MPT, respectively. A different brain region sample comparison shows that organoids grafted to PFC have obtained cell fate close to those of host cells in PFC, other than HIP, which may be regulated by the abundant expression of dopamine (DA) and acetylcholine (Ach) in PFC. Meanwhile, morphological complexity of human astrocyte grafts is greater in PFC than in HIP. DA and Ach both activate the calcium activity and increase morphological complexity of astrocytes in vitro. This study demonstrates that human brain organoids receive host niche factor regulation after transplantation, resulting in the alignment of grafted cell fate with implanted brain regions, which may contribute to a better understanding of cell transplantation and regenerative medicine.

The aim of this study was to investigate effects of dietary metformin supplementation on growth performance, liver function, and glucose metabolism of rice field eel (Monopterus albus) fed high carbohydrate diets (HCDs). Four isonitrogenous and isolipid diets were formulated, different in 15% α-starch (LC), 35% α-starch (HC), and 35% α-starch supplemented with 0.25% (HCM0.25) and 0.5% metformin (HCM0.5), respectively. After 8 weeks, the results showed that HCDs did not affect growth performance, but reduced the activities of amylase and trypsin, and damaged liver function together with the increase of hepatic glycogen content. HCM0.25 did not affect whereas HCM0.5 damaged the growth performance. Activities of amylase in HCM0.25 group and trypsin in both HCM0.25 and HCM0.50 groups were increased. While HCM0.25 lowered serum AST and ALT activities, HCM0.5 showed an increase. HCM0.25 caused a reduction in vacuoles size and a increase in nuclei number, whereas HCM0.5 failed to induce similar effects. The liver glycogen content was reduced by both HCM0.25 and HCM0.5 whereas the muscle glycogen content remained stable. Both HCM0.25 and HCM0.5 enhanced glycolysis–related enzymatic activities (PFK, PK) in liver, while reducing gluconeogenesis (FBPase). Similarly, both treatments upregulated gene expression of pk in liver, while downregulated g6pase, fbpase and pepck. Moreover, HCM0.25 and HCM0.5 increased PFK, G6Pase, FBPase and PEPCK activity in muscle, with HCM0.25 further upregulating gene expressions of hk, pfk, g6pase and pepck. Both treatments downregulated the gene expression of g6pd in muscle, whereas only HCM0.25 upregulated ampkα1, tbc1d1 and glut4. In summary, dietary 0.25% metformin improved liver function, reduced liver glycogen content, and regulated glucose metabolism and AMPKα-TBC1D1-GLUT4 pathway. However, 0.50% metformin did not demonstrate positive effects and even had adverse effects on growth performance.

Abstract Compound plant extracts (CPE) are beneficial for aquatic animals on growth performance and antioxidant capacity. A 56‐day experiment was conducted to investigate its positive effect on rice field eel. The fish were fed a commercial diet and supplementing CPE (mainly containing eucommia polysaccharides, reducing sugar) at 0, 0.8, 1.6, 2.4, and 3.2 g/kg. Results showed that dietary CPE significantly increased weight gain and specific growth rate (p

Summary: Background: A variety of symptoms, particularly cognitive, psychiatric and neurological symptoms, may persist for a long time among individuals recovering from COVID-19. However, the underlying mechanism of these brain abnormalities remains unclear. This study aimed to investigate the long-term neuroimaging effects of COVID-19 infection on brain functional activities using resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Fifty-two survivors 27 months after infection (mild-moderate group: 25 participants, severe-critical: 27 participants), from our previous community participants, along with 35 healthy controls, were recruited to undergo fMRI scans and comprehensive cognitive function measurements. Participants were evaluated by subjective assessment of Cognitive Failures Questionnaire-14 (CFQ-14) and Fatigue Scale-14 (FS-14), and objective assessment of Montreal Cognitive Assessment (MoCA), N-back, and Simple Reaction Time (SRT). Each had rs-fMRI at 3T. Measures such as the amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo) were calculated. Findings: Compared with healthy controls, survivors of mild-moderate acute symptoms group and severe-critical group had a significantly higher score of cognitive complains involving cognitive failure and mental fatigue. However, there was no difference of cognitive complaints between two groups of COVID-19 survivors. The performance of three groups was similar on the score of MoCA, N-back and SRT. The rs-fMRI results showed that COVID-19 survivors exhibited significantly increased ALFF values in the left putamen (PUT.L), right inferior temporal gyrus (ITG.R) and right pallidum (PAL.R), while decreased ALFF values were observed in the right superior parietal gyrus (SPG.R) and left superior temporal gyrus (STG.L). Additionally, decreased ReHo values in the right precentral gyrus (PreCG.R), left postcentral gyrus (PoCG.L), left calcarine fissure and surrounding cortex (CAL.L) and left superior temporal gyrus (STG.L). Furthermore, significant negative correlations between the ReHo values in the STG.L, and CFQ-14 and mental fatigue were found. Interpretation: This long-term study suggests that individuals recovering from COVID-19 continue to experience cognitive complaints, psychiatric and neurological symptoms, and brain functional alteration. The rs-fMRI results indicated that the changes in brain function in regions such as the putamen, temporal lobe, and superior parietal gyrus may contribute to cognitive complaints in individuals with long COVID even after 2-year infection. Funding: The National Programs for Brain Science and Brain-like Intelligence Technology of China, the National Natural Science Foundation of China, Natural Science Foundation of Beijing Municipality of China, and the National Key Research and Development Program of China.

Abstract Background Ferroptosis is a new form of nonapoptotic and iron-dependent type of cell death. Glutathione peroxidase-4 (GPX4) plays an essential role in anti-ferroptosis by reducing lipid peroxidation. Although acute myeloid leukemia (AML) cells, especially relapsed and refractory (R/R)-AML, present high GPX4 levels and enzyme activities, pharmacological inhibition of GPX4 alone has limited application in AML. Thus, whether inhibition of GPX4 combined with other therapeutic reagents has effective application in AML is largely unknown. Methods Lipid reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) assays were used to assess ferroptosis in AML cells treated with the hypomethylating agent (HMA) decitabine (DAC), ferroptosis-inducer (FIN) RAS-selective lethal 3 (RSL3), or their combination. Combination index (CI) analysis was used to assess the synergistic activity of DAC + RSL3 against AML cells. Finally, we evaluated the synergistic activity of DAC + RSL3 in murine AML and a human R/R-AML-xenografted NSG model in vivo. Results We first assessed GPX4 expression and found that GPX4 levels were higher in AML cells, especially those with MLL rearrangements, than in NCs. Knockdown of GPX4 by shRNA and indirect inhibition of GPX4 enzyme activity by RSL3 robustly induced ferroptosis in AML cells. To reduce the dose of RSL3 and avoid side effects, low doses of DAC (0.5 µM) and RSL3 (0.05 µM) synergistically facilitate ferroptosis by inhibiting the AMP-activated protein kinase (AMPK)-SLC7A11-GPX4 axis. Knockdown of AMPK by shRNA enhanced ferroptosis, and overexpression of SLC7A11 and GPX4 rescued DAC + RSL3-induced anti-leukemogenesis. Mechanistically, DAC increased the expression of MAGEA6 by reducing MAGEA6 promoter hypermethylation. Overexpression of MAGEA6 induced the degradation of AMPK, suggesting that DAC inhibits the AMPK-SLC7A11-GPX4 axis by increasing MAGEA6 expression. In addition, DAC + RSL3 synergistically reduced leukemic burden and extended overall survival compared with either DAC or RSL3 treatment in the MLL-AF9-transformed murine model. Finally, DAC + RSL3 synergistically reduced viability in untreated and R/R-AML cells and extended overall survival in two R/R-AML-xenografted NSG mouse models. Conclusions Our study first identify vulnerability to ferroptosis by regulating MAGEA6-AMPK-SLC7A11-GPX4 signaling pathway. Combined treatment with HMAs and FINs provides a potential therapeutic choice for AML patients, especially for R/R-AML.

This paper introduces a novel hybrid parking system that integrates stationary charging piles (SCPs) and mobile charging robots (MCRs) to optimize urban parking utility. The model categorizes parking spaces based on the presence of SCPs, considering customer behavior including improper parking. It also introduces an operational algorithm—Earliest Available Device First (EADF)—to manage real-time scheduling of MCRs efficiently. Through strategic planning and operational management, the system aims to enhance social welfare by balancing cost-efficiency with flexible charging solutions. We evaluate our approach based on real-world data, demonstrating how MCRs significantly improve both the strategic and accumulated operational aspects of urban parking facilities. The results showcase the potential of hybrid systems in urban environments, promoting higher utility and cost-effective management.

Abstract Intrauterine adhesion (IUA) is characterized by endometrial fibrosis. S100A8/A9 plays an important role in inflammation and fibroblast activation. However, the role of S100A8/A9 in IUA remains unclear. In this study, we collect normal and IUA endometrium to verify the expression of S100A8/A9. Human endometrial stromal cells (hEnSCs) are isolated to evaluate fibrosis progression after S100A8/A9 treatment. A porcine IUA model is established by electrocautery injury to confirm the therapeutic effect of menstrual blood-derived stromal cells (MenSCs) on IUA. Our study reveals increased S100A8/A9 expression in IUA endometrium. S100A8/A9 significantly enhances hEnSCs proliferation and upregulates fibrosis-related and inflammation-associated markers. Furthermore, S100A8/A9 induces hEnSCs fibrosis through the RAGE-JAK2-STAT3 pathway. Transplantation of MenSCs in a porcine IUA model notably enhances angiogenesis, mitigates endometrial fibrosis and downregulates S100A8/A9 expression. In summary, S100A8/A9 induces hEnSCs fibrosis via the RAGE-JAK2-STAT3 pathway, and MenSCs exhibit marked effects on endometrial restoration in the porcine IUA model.

Purpose: Male overweight and obesity could affect sperm quality and reproductive health. However, the impact of body mass index (BMI) on assisted reproductive technology (ART) outcomes in oligospermia and/or asthenospermia patients is yet lacking. This study aims to assess the impact of paternal BMI on ART and neonatal outcomes among oligozoospermia and/or asthenospermia patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Materials and Methods: In this study, 2,075 couples undergoing their first fresh embryo transfer between January 2015 and June 2022 were recruited. Following the World Health Organization’s (WHO’s) categories, couples were stratified into three cohorts based on paternal BMI: normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), and obese (≥30.0 kg/m2). Modified Poisson regression models were used to assess the associations of paternal BMI with fertilization, in vitro embryonic development, and pregnancy outcomes. Logistic regression models were performed to investigate the associations of paternal BMI with pregnancy loss and neonatal outcomes. Furthermore, stratified analyses were performed based on fertilization methods, male infertility cause, and maternal BMI. Results: Higher paternal BMI is associated with a lower likelihood of achieving normal fertilized (p-trend=0.002), Day 3 transferable (p-trend=0.007), and high-quality embryos (p-trend=0.046) in IVF cycles, rather than in ICSI cycles. Paternal BMI of oligospermia or asthenospermia was negatively correlated with day 3 transferable (p-trend=0.013 and 0.030) and highquality embryos (p-trend=0.024 and 0.027). Moreover, for neonatal outcomes, paternal BMI was positively associated with macrosomia (p-trend=0.019), large for gestational age (LGA) (p-trend=0.031), and very LGA (p-trend=0.045). Conclusions: Our data suggested that higher paternal BMI was associated with fetal overgrowth, reduced fertilization, and embryonic development potential. Among males with oligospermia and/or asthenospermia, the impact of overweight and obesity on the choice of fertilization method and the long-term effects on their offspring need to be further investigated.

Objective To observe the therapeutic effects of mesenchymal stem cell-derived exosomes on rosacea. Methods Seventy-eight patients with rosacea, including 39 PPR type and 39 ETR type, were enrolled at the Changsha Mylike Cosmetic Hospital from January 2021 to January 2022. All patients were treated with microneedling infusion of mesenchymal stem cell-derived exosomes (MSC-exo) once a month for three months. The clinical efficacy, adverse reactions, erythema assessment scale (CEA), patient physical evaluation (PSA), investigators' global assessment (IGA) scale and skin barrier function were compared between the two groups. Results Treatment with MSC-exo significantly decreased both CEA and IGA scales, EI and TEWL, while increasing stratum corneum hydration (P

Islands are an important part of China's marine ecological protection, with significant implications for supporting economic and social development, maintaining maritime ecological security, and safeguarding national maritime rights and interests. Currently, China has undertaken many marine ecological restoration projects involving islands, and the restoration effects have become evident. The evaluation of island ecological restoration effectiveness is an important tool for assessing the effectiveness of ecological restoration work. Present evaluation methods mainly focus on the assessment of engineering technical indicators, lacking an overall examination of the effectiveness of restoration projects. This paper constructed a comprehensive evaluation index system for the effectiveness of island ecological restoration from three aspects, including the completion of island ecological restoration projects, the restoration effectiveness of island ecosystem functions, and the spillover benefits of island ecological restoration, striving to scientifically, comprehensively, and objectively evaluate the effectiveness of island ecological restoration.

Abstract Background Although multiple measures of blood pressure variability (BPV) have been proposed, whether they are better than mean blood pressure in predicting target organs is unclear. We aimed to determine the relationship between short term BPV and target organ injury. Methods This study was a retrospective study, and 635 inpatients in the Department of Cardiology from 2015 to 2020 were selected. We divided participants into four groups on the basis of the quartiles of BPV. One‐way analysis of variance was used to compare the differences between the groups, and linear regression was used to analyze the relationship between BPV and target organ damage. Results The average age of 635 patients was 74.36 ± 6.50 years old. Among them, 354 of 627 patients had diminished renal function (56.5%), 221of 604 patients had associated left ventricular hypertrophy (36.6%), and 227 of 231 patients had carotid plaque formation (98.3%). The baseline data indicated significant differences in fasting glucose, total cholesterol, low‐density lipoprotein, creatinine, glomerular filtration rate, sex, calcium channel blocker use, and the rate of diminished renal function. Multiple linear regression analysis showed that BPV was negatively correlated with renal injury (creatinine: r = 0.306, p

Despite the associations of dietary patterns and air pollution with human reproductive health have been demonstrated, the interaction of maternal preconception diet and PM2.5 and its components exposure on in vitro fertilization (IVF) treatment outcomes has not been investigated. A total of 2688 couples from an ongoing prospective cohort were included. Principle component analysis with varimax rotation was performed to determine dietary patterns. One-year and 85-day average PM2.5 and its components exposure levels before oocyte retrieval were estimated. Generalized linear regression models were conducted to assess the association of dietary patterns and PM2.5 and its components exposure with IVF outcomes. Interactive effects of dietary patterns on the association between PM2.5 and its components and IVF outcomes were evaluated by stratified analyses based on different dietary patterns. A positive association between the “Fruits-Vegetables-Dairy” pattern and normal fertilization (p-trend = 0.009), Day 3 available embryos (p-trend = 0.048), and top-quality embryos (p-trend = 0.041) was detected. Conversely, women with higher adherence to the “Puffed food-Bakery-Candy” pattern were less likely to achieve Day 3 available embryos (p-trend = 0.042) and top-quality embryos (p-trend = 0.030), clinical pregnancy (p-trend = 0.049), and live birth (p-trend = 0.020). Additionally, increased intake of animal organs and seafood improved the odds of live birth (p-trend = 0.048). Exposure to PM2.5, SO42-, organic matter (OM), and black carbon (BC) had adverse effects on embryo development and pregnancy outcomes. Furthermore, our findings indicated that the effects of PM2.5 components exposure on normal fertilization and embryo quality were modified by the “Grains-Tubers-Legumes”. Moreover, moderate intake of animal organs and seafood appeared to attenuate the effect of NO3- and NH4+ on the risk of early abortion. Our findings provide human evidence of the interaction between dietary patterns and PM2.5 exposure on IVF outcomes during preconception, implicating the potential for dietary interventions in infertile women to improve reproductive outcomes under conditions of unavoidable ambient air-pollutant exposure.

Introduction: Aristolochic acid nephropathy (AAN) is a kidney injury syndrome caused by aristolochic acids exposure. Our study used label-free quantitative proteomics to delineate renal protein profiles and identify key proteins after exposure to different doses of aristolochic acid I (AAI).Methods: Male C57BL/6 mice received AAI (1.25 mg/kg/d, 2.5 mg/kg/d, or 5 mg/kg/d) or vehicle for 5 days.Results and discussion: The results showed that AAI induced dose-dependent nephrotoxicity. Differences in renal protein profiles between the control and AAI groups increased with AAI dose. Comparing the control with the low-, medium-, and high-dose AAI groups, we found 58, 210, and 271 differentially expressed proteins, respectively. Furthermore, protein-protein interaction network analysis identified acyl-CoA synthetase medium-chain family member 3 (Acsm3), cytochrome P450 family 2 subfamily E member 1 (Cyp2e1), microsomal glutathione S-transferase 1 (Mgst1), and fetuin B (Fetub) as the key proteins. Proteomics revealed that AAI decreased Acsm3 and Cyp2e1 while increasing Mgst1 and Fetub expression in mice kidneys, which was further confirmed by Western blotting. Collectively, in AAI-induced nephrotoxicity, renal protein profiles were dysregulated and exacerbated with increasing AAI dose. Acsm3, Cyp2e1, Mgst1, and Fetub may be the potential therapeutic targets for AAN.

BackgroundGrip strength has been shown to be associated with chronic renal insufficiency, but the relationship between grip strength and albuminuria has not been confirmed. In this study, we used NHANES data to explore the association between grip strength and albuminuria in a US population.MethodsIn this analytical study, we utilized data sourced from the National Health and Nutrition Examination Survey (NHANES), specifically spanning the years 2011 to 2014. The dataset included 9,638 participants aged 20 years or older. After adjusting for potential confounders, multiple regression models were developed to infer the interrelationship between grip strength and albumin to creatinine ratio (ACR), and subgroup analyses were conducted.ResultsAfter adjusting for all covariates, ACR by 0.49 mg/g [−0.49 (95% CI: −0.93, −0.04)] for each 1 kg increase in grip strength decreased. Subgroup analysis showed that gender, age, hyperlipidemia, hypertension, diabetes mellitus, smoking, alcohol consumption and body mass index did not influence the negative correlation between grip strength and albuminuria.ConclusionThere is a negative correlation between grip strength and albuminuria in the general U.S. population.

BackgroundNeonatal screening for inherited metabolic diseases (IMDs) has been revolutionized by tandem mass spectrometry (MS/MS). This study aimed to enhance neonatal screening for IMDs using machine learning (ML) techniques.MethodsThe study involved the analysis of a comprehensive dataset comprising 309,102 neonatal screening records collected in the Ningbo region, China. An advanced ML system model, encompassing nine distinct algorithms, was employed for the purpose of predicting the presence of 31 different IMDs. The model was compared with traditional cutoff schemes to assess its diagnostic efficacy. Additionally, 180 suspected positive cases underwent further evaluation.ResultsThe ML system exhibited a significantly reduced positive rate, from 1.17% to 0.33%, compared to cutoff schemes in the initial screening, minimizing unnecessary recalls and associated stress. In suspected positive cases, the ML system identified 142 true positives with high sensitivity (93.42%) and improved specificity (78.57%) compared to the cutoff scheme. While false negatives emerged, particularly in heterozygous carriers, our study revealed the potential of the ML system to detect asymptomatic cases.ConclusionThis research provides valuable insights into the potential of ML in pediatric medicine for IMD diagnosis through neonatal screening, emphasizing the need for accurate carrier detection and further research in this domain.

Abstract Objective To determine the effect of different translocation characteristics on fertilization rate and blastocyst development in chromosomal translocation patients. Methods This retrospective cohort study was conducted at the Third Affiliated Hospital of Zhengzhou University From January 2017 to December 2022.All couples were diagnosed as reciprocal translocation or Robertsonian translocation by karyotype of peripheral blood lymphocytes test. After adjusting for confounding factors, the effect of chromosomal rearrangement characteristics, such as carrier sex, translocation type, chromosome length and break sites, on fertilization rate and embryo development were analysed separately using multiple linear regression. Results In cases of Robertsonian translocation (RobT), the carrier sex plays an independent role in fertilization rate, and the male carriers was lower than that of female carriers (76.16% vs.86.26%, P = 0.009). In reciprocal translocation (RecT), the carrier sex, chromosome types and break sites had no influence on fertilization rate, blastocyst formation rate (P > 0.05). However, patients with human longer chromosomal (chromosomes 1–5) translocation have a lower available blastocyst formation rate (Group AB vs. Group CD: 41.49%vs.46.01%, P = 0.027). For male carriers, the translocation types was an independent factor affecting the fertilization rate, and the RobT was the negative one (B = − 0.075, P = 0 0.009). In female carriers, we did not observe this difference (P = 0.227). Conclusions In patients with chromosomal translocation, the fertilization rate may be influenced by carrier sex and translocation type, chromosomes 1–5 translocation may adversely affect the formation of available blastocysts. Break sites have no role in fertilization and blastocyst development.

ABSTRACTLentinan (LNT) is extracted from the fruiting body of Lentinus edodes. Its active ingredient is β−1,3-dextran and has many biological activities, but its rheological characteristics and antibacterial mechanism when mixed with saliva are rarely reported. In this study, the LNT and artificial saliva (AS) mixture was used to investigate the rheological analysis and antibacterial mechanism against Streptococcus mutans (S. mutans). The results showed that the apparent viscosity of the mixture was positively correlated with the concentration, showing a shear thinning behavior and a “non-Newtonian fluid” with a pseudoplastic behavior with the increase of shear rate. In dynamic rheology, the 8% and 6% mixtures became a gel trend and viscoelastic properties, showing elasticity of weak gel at low frequencies and liquid-like viscosity at high frequencies. Moreover, the compound could damage the structures of S. mutans and increased the leakage of intracellular macromolecules, electrical conductivity, and activities of alkaline phosphatase (AKP) and β-galactoside but inhibited acid production, fluorescence intensity, and ATP synthesis by decreasing the levels of glucokinase (glk), acetate kinase (ackA), pyruvate kinase (pykf), phosphoglycerate kinase (pgk), 6-phosphofructokinase (pfk) in the glycolysis pathway. These results indicate that LNT plays a dominant role in the oral processing and antibacterial mechanism against S. mutans. It can provide an excellent theoretical basis for studying LNT as a functional food raw material.

Taopian is a traditional Chinese pastry made from cooked glutinous rice flour. The effects of heat–moisture treatment (110 °C, 4 h; moisture contents 12–36%, w/w) on the preparation of cooked glutinous rice flour and taopian made from it were compared with the traditional method of stir-frying (180 °C, 30 s). The color of heat–moisture-treated (HMT) flours was darker. HMT flours exhibited a larger mean particle size (89.5–124 μm) and a greater relative crystallinity of starch (23.08–42.92%) and mass fractal dimension (1.77–2.28). The flours exhibited water activity in the range of 0.589–0.631. Although the oil-binding capacity of HMT flours was largely comparable to that of stir-fried flours, HMT flours exhibited a lower water absorption index. Accordingly, the taopian produced with HMT flours exhibited a lower brightness, accompanied by a stronger reddening and yellowing. In addition, more firmly bound water was observed in the taopian produced with HMT flour. The taopian made with HMT flour with a moisture content of 24% exhibited moderate hardness, adhesiveness and cohesiveness and received the highest score for overall acceptability (6.80). These results may be helpful to improve the quality of taopian by applying heat–moisture treatment in the preparation of cooked glutinous rice flour.

Conclusions: The combination of GLP-1 RAs, DPP-4i, and SGLT-2i can effectively lower HbA1c and FPG in T2DM patients who have poor therapeutic effects on basic insulin combined with metformin/sulfonylureas, respectively. Compared to placebo, GLP-1 RAs can significantly reduce body weight and basic insulin dosage, while DPP-4i and SGLT-2i have a lower risk of hypoglycemia.

Abstract Background Intrauterine adhesion (IUA) is a recurrent and refractory reproductive dysfunction disorder for which menstrual blood-derived stromal cells (MenSCs) might be a promising intervention. We reported that administration of MenSCs-derived exosomes (MenSCs-EXO) could achieve similar therapeutic effects to MenSCs transplantation, including alleviating endometrial fibrosis and improving fertility in IUA rats. The mass spectrometry sequencing result suggested that UBR4, a member of the proteasome family, was abundantly enriched in MenSCs-EXO. This study aimed to investigate the key role of UBR4 in MenSCs-EXO for the treatment of IUA and the specific molecular mechanism. Results UBR4 was lowly expressed in the endometrial stromal cells (EndoSCs) of IUA patients. MenSCs-EXO treatment could restore the morphology of IUA endometrium, reduce the extent of fibrosis, and promote endometrial and vascular proliferation. Knockdown of UBR4 in MenSCs did not affect the characteristics of exosomes but attenuated the therapeutic effect of exosomes. UBR4 in MenSCs-EXO could alleviate endometrial fibrosis by boosting YAP ubiquitination degradation and promoting YAP nuclear-cytoplasmic translocation. Moreover, P65 could bind to the UBR4 promoter region to transcriptionally promote the expression level of UBR4 in MenSCs. Conclusion Our study clarified that MenSCs-EXO ameliorated endometrial fibrosis in IUA primarily by affecting YAP activity mediated through UBR4, while inflammatory signaling P65 may affect UBR4 expression in MenSCs to enhance MenSCs-EXO therapeutic effects. This revealed a novel mechanism for the treatment of IUA with MenSCs-EXO, proposing a potential option for the clinical treatment of endometrial injury.

In this study, we designed two series of novel anthraquinone-based benzenesulfonamide derivatives and their analogues as potential carbonic anhydrase inhibitors (CAIs) and evaluated their inhibitory activities against off-target human carbonic anhydrase II (hCA II) isoform and tumor-associated human carbonic anhydrase IX (hCA IX) isoform. Most of these compounds exhibited good inhibitory activities against hCA II and IX. The compounds that exhibited the best hCA inhibition were further studied against the MDA-MB-231, MCF-7, and HepG2 cell lines under hypoxic and normoxic conditions. Additionally, the compounds exhibiting the best antitumor activity were subjected to apoptosis and mitochondrial membrane potential assays, which revealed a significant increase in the percentage of apoptotic cells and a notable decrease in cell viability. Molecular docking studies were performed to demonstrate the presence of numerous hydrogen bonds and hydrophobic interactions between the compounds and the active site of hCA. Absorption, distribution, metabolism, excretion (ADME) predictions showed that all of the compounds had good pharmacokinetic and physicochemical properties.

Abstract Background Intrauterine adhesion (IUA) is a reproductive dysfunction disease characterized by endometrial fibrosis, with limited therapeutic options and poor prognosis. Our previous studies confirmed that menstrual blood-derived stromal cells (MenSCs) effectively attenuated endometrial fibrosis in an animal model of IUA mainly through exosomes. This therapeutic effect can be enhanced by platelet-rich plasma (PRP), in which PDGFBB is an abundant growth factor. Therefore, we aimed to compare the effects of PRP and PDGFBB on the biological activities of MenSCs in vitro, and to further investigate the molecular mechanism of MenSCs-derived exosomes in alleviating endometrial fibrosis. Methods MenSCs were isolated for in vitro functional assays to examine the viability, migration, and stemness of MenSCs. Endometrial stromal cells (EndoSCs) were treated with 50 ug/ml of MenSCs-derived exosomes, obtained by differential ultracentrifugation extraction. The molecular mechanisms by which PDGFBB improves MenSCs and exosomes alleviate EndoSCs fibrosis were then explored using immunofluorescence, western blot, and co-immunoprecipitation. Results Both 100 ng/ml PDGFBB and 10% activated PRP promoted the proliferation, increased the S phase of cell cycle, and inhibited apoptosis of MenSCs in vitro. Compared with PRP, PDGFBB significantly promoted MenSCs migration. All of these effects were inhibited by sorafenib, a PDGFR-β inhibitor. PRP and PDGFBB activated AKT/NF-κB signaling pathway in MenSCs and increased the expression of P65 and OCT4. Moreover, pretreatment of PDGFBB did not increase the secretion of MenSCs but significantly increased the anti-fibrosis effects of MenSCs-derived exosomes on IUA-EndoSCs. MenSCs-derived exosomes attenuated SMAD3 phosphorylation and increased YAP ubiquitination, which reduced the binding of YAP/SMAD3. Pretreatment with PDGFBB amplified this effect. Conclusions In summary, PDGFBB could improve the biological functions of MenSCs via AKT/NF-κB signaling pathway, including viability, migration, and stemness. Our results indicated that PDGFBB amplified MenSCs-derived exosomes to attenuate endometrial fibrosis by inhibiting YAP activity, revealing a novel mechanism by which PRP enhanced the ability of MenSCs to repair tissue injury and providing a potential option for improving stem cell efficacy in IUA.

Abstract Aberrant activation of TGF-β signaling plays a pivotal role in cancer metastasis and progression. However, molecular mechanisms underlying the dysregulation of TGF-β pathway remain to be understood. Here, we found that SMAD7, a direct downstream transcriptional target and also a key antagonist of TGF-β signaling, is transcriptionally suppressed in lung adenocarcinoma (LAD) due to DNA hypermethylation. We further identified that PHF14 binds DNMT3B and serves as a DNA CpG motif reader, recruiting DNMT3B to the SMAD7 gene locus, resulting in DNA methylation and transcriptional suppression of SMAD7. Our in vitro and in vivo experiments showed that PHF14 promotes metastasis through binding DNMT3B to suppress SMAD7 expression. Moreover, our data revealed that PHF14 expression correlates with lowered SMAD7 level and shorter survival of LAD patients, and importantly that SMAD7 methylation level of circulating tumor DNA (ctDNA) can potentially be used for prognosis prediction. Together, our present study illustrates a new epigenetic mechanism, mediated by PHF14 and DNMT3B, in the regulation of SMAD7 transcription and TGF-β-driven LAD metastasis, and suggests potential opportunities for LAD prognosis.

Cracks will inevitably occur in concrete structural during the normal use phase due to load action, fatigue effect, and environmental corrosion. Concrete resistance can reflect some internal concrete damage. In this work, three-point bending tests were performed on concrete beams. We simultaneously measured the concrete beam resistance before and after cracking to investigate the feasibility of resistance measurement for achieving self-monitoring of concrete cracking and crack development. This work provides a methodology for the monitoring of engineering structures. It establishes a quantitative reference for the relationship between the number of steel fibers used and their conductive and mechanically sensitive properties.

Background: Acute kidney injury (AKI) induced by cisplatin remains a major impediment to the clinical application of cisplatin, necessitating urgent exploration for promising solutions. Huangqi-Danshen decoction (HDD), a Chinese herbal preparation, has been shown by our group to have a reno-protective effect in adenine-induced chronic kidney disease mice and diabetic db/db mice. However, the effect of HDD on cisplatin-induced AKI and its underlying mechanisms are unknown.Methods: The AKI model was established by intraperitoneal injection of cisplatin (20 mg/kg) in C57BL/6 mice. The mice in the treatment group were administrated with HDD (6.8 g/kg/d) for 5 consecutive days before cisplatin challenge. After 72 h cisplatin injection, blood and kidney tissue were subsequently collected for biochemical detection, histopathological evaluation, Western blot analysis, immunohistochemical staining, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling assay. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to detect changes in renal metabolites.Results: The results showed that HDD significantly reduced serum creatinine and blood urea nitrogen levels and alleviated renal histopathological injury in cisplatin-induced AKI mice. And HDD treatment demonstrated a significant inhibition in apoptosis, inflammation, and oxidative stress in AKI mice. Moreover, non-target metabolomics revealed that HDD significantly restored 165 altered metabolites in AKI mice. Subsequent enrichment analysis and pathway analysis of these metabolites indicated that nicotinate and nicotinamide metabolism was the primary pathway affected by HDD intervention. Further investigation showed that HDD could upregulate nicotinamide adenine dinucleotide (NAD+) biosynthesis-related enzymes quinolinate phosphoribosyltransferase, nicotinamide mononucleotide adenylyltransferase 1, and nicotinamide phosphoribosyltransferase to replenish NAD+ content in the kidney of AKI mice.Conclusion: In summary, HDD exerted a protective effect against cisplatin-induced AKI and suppressed apoptosis, inflammation, and oxidative stress in the kidney of AKI mice, which may be attributed to the modulation of NAD+ biosynthesis.

BackgroundDysregulation of feeding behavior leads to a variety of pathological manifestations ranging from obesity to anorexia. The foraging behavior of animals affected by food deficiency is not fully understood.MethodsHome-Cage system was used to monitor the behaviors. Immunohistochemical staining was used to monitor the trend of neuronal activity. Chemogenetic approach was used to modify neuronal activity.ResultsWe described here a unique mouse model of foraging behavior and unveiled that food deprivation significantly increases the general activities of mice with a daily rhythmic pattern, particularly foraging behavior. The increased foraging behavior is potentiated by food cues (mouthfeel, odor, size, and shape) and energy deficit, rather than macronutrient protein, carbohydrate, and fat. Notably, energy deficiency increases nocturnal neuronal activity in paraventricular hypothalamic nucleus (PVH), accompanying a similar change in rhythmic foraging behavior. Activating neuronal activity in PVH enhances the amplitude of foraging behavior in mice. Conversely, inactivating neuronal activity in PVH decreases the amplitude of foraging behavior and impairs the rhythm of foraging behavior.DiscussionThese results illustrate that energy status and food cues regulate the rhythmic foraging behavior via PVH neuronal activity. Understanding foraging behavior provides insights into the underlying mechanism of eating-related disorders.

Premature ovarian insufficiency (POI) is clinically irreversible and seriously damages female fertility. We previously demonstrated that menstrual blood stromal cells (MenSCs)-derived exosomes (EXOs) effectively improved ovarian functions in the POI rat model. In this study, we investigated whether TSP1 is the key component in EXOs to ameliorate ovarian functions and further explored the molecular mechanism of EXOs in improving granulosa cell (GCs) activities. Our results demonstrated that knockdown TSP1 significantly debilitated the therapeutic effect of EXOs on estrous cyclicity, ovarian morphology, follicle numbers and pregnancy outcomes in 4-vinylcyclohexene diepoxide (VCD) induced POI rat model. In addition, EXOs treatment significantly promoted the activities and inhibited the apoptosis of VCD induced granulosa cells in vitro. Moreover, EXOs stimulation markedly activated the phosphorylation of SMAD3(Ser425) and AKT(Ser473), up-regulated the expressions of BCL2 and MDM2 as well as down-regulated the expressions of CASPASE3, CASPASE8, P53 and BAX. All these effects were supressed by SIS3, a inhibitor of TGF1/SMAD3. Our study revealed the key role of TSP1 in EXOs in improving POI pathology, restoring ovarian functions and GCs activities, andprovided a promising basis for EXOs in the treatment of ovarian dysfunction.

To improve the quantitative detection efficiency of chemical analysis and reduce the detection cost, the sample pass rate was estimated and mathematical statistics were used to calculate the optimal group size (Kopt) of the composite testing to save on the maximum workload. A quantitative composite testing model was developed based on chemical analysis measurement uncertainty. Using this model, the maximum allowable number of composited samples (Kmax) is first calculated using parameters of regulated limits (L), limit of quantification (LOQ), and method measured uncertainty (Urel) to ensure that the sensitivity of the composite testing can meet the limit requirements. Finally, the appropriate composite group size (Ka) can be obtained by creating a balance between Kopt, Kmax, and the practical information used for that particular test. Furthermore, based on a constructed model, a practical quantitative composite testing method of 3–10 samples was established for the routine detection of toy phthalates (PAEs). The experimental results showed that the quantitative limits of 7 PAEs were 9.1–41.8 mg/kg, the relative expansion uncertainties were 16.6%–23.2%, and the recovery rates were 91.0%–112.3%, with a relative deviation of less than 10%. All these meet international PAEs standards. Compared with the traditional individual and qualitative composite testing, this model will not decrease the detection sensitivity, but can save up to 17.9%–80.4% of the workload when it is employed in toy PAEs testing with the pass rate of 80%–99%. This quantitative composite testing method will be implemented in the coming revision of ISO 8124-6 toy PAEs standards.

Target detection for hyperspectral images (HSIs) is one of the significant techniques in remote sensing data processing. Targets generally comprise various object categories with complex features and of varying sizes. Target detection is often used in complex application scenarios in which accurately and efficiently acquiring detection results can be challenging. The development of advanced target detection approaches is becoming increasingly necessary in both military and civilian fields. This article proposes an alternating direction method of multiplier (ADMM)-based parallel approach for hyperspectral target detection. Different from existing methods performing target detection solely on HSIs, our approach performs the fusion of hyperspectral and multispectral data to leverage both spectral and spatial information prior. For each task or data partition, the parallel processing of the computation load on multiple computing nodes can substantially reduce the computation time. In addition, we introduce a novel weighted ADMM, which takes the influence of different variables on convergence into account, to further enhance the computational efficiency of the target detection model. Experiments on real-world HSI datasets demonstrate that our proposed parallel method not only produces more accurate detection results than direct detection methods, but also achieves significant acceleration ratio compared with the serial processing flow.

Abstract Introduction Compared with traditional fundus examination techniques, ultra-widefield fundus (UWF) images provide 200° panoramic images of the retina, which allows better detection of peripheral retinal lesions. The advent of UWF provides effective solutions only for detection but still lacks efficient diagnostic capabilities. This study proposed a retinal lesion detection model to automatically locate and identify six relatively typical and high-incidence peripheral retinal lesions from UWF images which will enable early screening and rapid diagnosis. Methods A total of 24,602 augmented ultra-widefield fundus images with labels corresponding to 6 peripheral retinal lesions and normal manifestation labelled by 5 ophthalmologists were included in this study. An object detection model named You Only Look Once X (YOLOX) was modified and trained to locate and classify the six peripheral retinal lesions including rhegmatogenous retinal detachment (RRD), retinal breaks (RB), white without pressure (WWOP), cystic retinal tuft (CRT), lattice degeneration (LD), and paving-stone degeneration (PSD). We applied coordinate attention block and generalized intersection over union (GIOU) loss to YOLOX and evaluated it for accuracy, sensitivity, specificity, precision, F1 score, and average precision (AP). This model was able to show the exact location and saliency map of the retinal lesions detected by the model thus contributing to efficient screening and diagnosis. Results The model reached an average accuracy of 96.64%, sensitivity of 87.97%, specificity of 98.04%, precision of 87.01%, F1 score of 87.39%, and mAP of 86.03% on test dataset 1 including 248 UWF images and reached an average accuracy of 95.04%, sensitivity of 83.90%, specificity of 96.70%, precision of 78.73%, F1 score of 81.96%, and mAP of 80.59% on external test dataset 2 including 586 UWF images, showing this system performs well in distinguishing the six peripheral retinal lesions. Conclusion Focusing on peripheral retinal lesions, this work proposed a deep learning model, which automatically recognized multiple peripheral retinal lesions from UWF images and localized exact positions of lesions. Therefore, it has certain potential for early screening and intelligent diagnosis of peripheral retinal lesions.

Objective: This study aimed to assess the effects of coronary collateral circulation (CCC) on the prognosis of patients with chronic total occlusion (CTO) under different treatment strategies. Methods: We analyzed a total of 1124 patients who were diagnosed with CTO and divided them into groups with good CCC (grade 2 to 3, n = 539) or poor CCC (grade 0 to 1, n = 531). The primary outcome was cardiac death during follow-up; the secondary outcome was major adverse cardiovascular events (MACEs). We also performed subgroup analyses in groups with and without CTO revascularization (CTO-R and CTO-NR, respectively), and sensitivity analyses excluding patients who received failed CTO-PCI to further investigate the effect of CCC. Results: During a median follow-up duration of 23 months, we did not detect any significant differences between the good CCC group and the poor CCC group in terms of cardiac death (4.2% vs 4.1%; adjusted hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.56–1.83; p = 0.970) and MACEs (23.6% vs 23.2%; adjusted HR, 1.07; 95% CI, 0.84–1.37; p = 0.590). Subgroup analyses according to CTO revascularization showed similar results. In addition, we observed no differences in sensitivity analyses when patients who received failed CTO-PCI were excluded. Conclusion: Good CCC was not associated with a lower risk of cardiac death or MACEs among patients with CTO, regardless of whether the patients received CTO revascularization treatment.

Abstract Purpose The objective of the manuscript is to propose a hybrid algorithm combining the improved BM25 algorithm, k-means clustering, and BioBert model to better determine biomedical articles utilizing the PubMed database so, the number of retrieved biomedical articles whose content contains much similar information regarding a query of a specific disease could grow larger. Design/methodology/approach In the paper, a two-stage information retrieval method is proposed to conduct an improved Text-Rank algorithm. The first stage consists of employing the improved BM25 algorithm to assign scores to biomedical articles in the database and identify the 1000 publications with the highest scores. The second stage is composed of employing a method called a cluster-based abstract extraction to reduce the number of article abstracts to match the input constraints of the BioBert model, and then the BioBert-based document similarity matching method is utilized to obtain the most similar search outcomes between the document and the retrieved morphemes. To realize reproducibility, the written code is made available on https://github.com/zzc1991/TREC_Precision_Medicine_Track . Findings The experimental study is conducted based on the data sets of TREC2017 and TREC2018 to train the proposed model and the data of TREC2019 is used as a validation set confirming the effectiveness and practicability of the proposed algorithm that would be implemented for clinical decision support in precision medicine with a generalizability feature. Originality/value This research integrates multiple machine learning and text processing methods to devise a hybrid method applicable to domains of specific medical literature retrieval. The proposed algorithm provides a 3% increase of P@10 than that of the state-of-the-art algorithm in TREC 2019.

The systematic exploration of the application prospects of lotus stem fibers (LSFs) in natural composites is significantly important for the development of green, lightweight, functional biomass materials and products. In this study, the physical and chemical properties, micro/nano structures, micromechanical characteristics, cellulose crystallinity, and thermal stability of LSFs were systematically explored. The density, microstructure, and nanoindentation analyses revealed that the LSF is a lightweight natural fiber with a high modulus (11.2–11.7 GPa) and a good hardness (0.41–0.57 GPa). The transmission electron microscopy analysis indicated the existence of four types of sclerenchyma cells in a gradient distribution in the epidermis and exodermis of the LS. The chemical analysis, X-ray diffraction, and Fourier transform infrared spectroscopy indicated that the outer-layer LSFs have a high cellulose content (44.73%), high relative crystallinity index (49.2%) of cellulose, and small cellulose crystallite size (2.2 nm). As a result, these LSFs possess good mechanical properties.

Abstract Background Anthocyanins are widely applied as a marker for haploid identification after haploid induction in maize. However, the factors affecting anthocyanin biosynthesis in immature embryos and the genes regulating this process remain unclear. Results In this study, we analyzed the influence of genetic background of the male and female parents, embryo age and light exposure on anthocyanin accumulation in embryos. The results showed that light exposure was the most crucial factor enhancing the pigmentation of immature embryos. The identification accuracy of haploid embryos reached 96.4% after light exposure, but was only 11.0% following dark treatment. The total anthocyanin content was 7-fold higher in immature embryos cultured for 24 h under light conditions compared to embryos cultured in the dark. Transcriptome analysis revealed that the differentially expressed genes between immature embryos cultured for 24 h in dark and light chambers were significantly enriched in the pathways of flavonoid, flavone, flavonol and anthocyanin biosynthesis. Among the genes involved in anthocyanin biosynthesis, five up-regulated genes were identified: F3H, DFR, ANS, F3′H and the MYB transcription factor-encoding gene C1. The expression patterns of 14 selected genes were confirmed using quantitative reverse transcription-polymerase chain reaction. Conclusion Light is the most important factor facilitating anthocyanin accumulation in immature embryos. After 24 h of exposure to light, the expression levels of the structural genes F3H, DFR, ANS, F3′H and transcription factor gene C1 were significantly up-regulated. This study provides new insight into the factors and key genes regulating anthocyanin biosynthesis in immature embryos, and supports improved efficiency of immature haploid embryo selection during doubled haploid breeding of maize.

In present study, Rhizopus chinensis 12 mixed fermentation with Bacillus sp. DU-106 were performed to improve the quality and flavor of Semen Sojae Praeparatum (SSP). The levels of physicochemical characteristics, bioactive compounds, free amino acids, and volatile components during the mixed fermentation process were monitored. Compared to SSP fermented only with R. chinensis 12, the levels of physicochemical characteristics were not obviously changed after mixed fermentation. However, thrombolytic enzyme activity and soy isoflavone content after mixed fermentation were significantly higher when compared to those of SSP fermented only with R. chinensis 12, and reached to 3927.84 IU/g and 3.91 mg/g, respectively. The amount of bitter amino acids and umami amino acids after mixed fermentation slightly lower than those of SSP fermented only with R. chinensis 12. The contents of flavor composition were considerably altered after mixed fermentation, of which, the pyrazine prevailed in SSP fermented only with R. chinensis 12, while, alkane predominated in SSP after mixed fermentation. Overall, the Rhizopus chinensis 12 mixed fermentation with Bacillus sp. DU-106 contributed to improve the thrombolytic activity, free amino acid content, and flavors of SSP.

AbstractCircular ribonucleic acids (circRNAs) are single-stranded RNAs with covalently closed-loop structures that lack terminal 5′ caps and 3′ poly-(A) tails. Recent evidence confirmed that some circRNAs can be translated into proteins. More importantly, there is a growing body of evidence that dysregulation of circRNAs is closely associated with the development of human diseases, especially malignant tumors. CircZNF609 is a novel circular RNA with an open reading frame and an internal ribosomal entry site that can interact with microRNAs and mRNAs and be translated into proteins. Studies have shown that circZNF609 is abnormally expressed in various human diseases, especially malignant tumors such as hepatocellular carcinoma, nasopharyngeal carcinoma, colorectal cancer and glioma, which lead to the occurrence and development of diseases. This article attempts to provide a comprehensive overview of the structural properties of circZNF609 discovered so far and focuses on the pathogenesis of circZNF609 in human diseases and its potential clinical application value. Finally, we elaborate on the directions of future investigations of this molecule.