Diffuse large B-cell lymphoma with central nervous system symptoms during the maintenance therapy of acute lymphoblastic leukemia: a case report and literature review.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) secondary to acute lymphoblastic leukemia (ALL) is a rare disease with poor prognosis, usually attributed to delayed diagnosis. To date, only four cases of ALL developing DLBCL have been reported, while none of them exhibiting central nervous system (CNS) symptoms. CASE DESCRIPTION: Here, we report an unusual case of a 15-year-old boy diagnosed with ALL and treated based on the SCCLG-ALL 2016 protocol. While he was receiving maintenance treatment, the patient developed dizziness and vomiting. An Epstein-Barr virus (EBV)-positive DLBCL with CNS involvement was diagnosed from inguinal lymph nodes biopsy, EBV DNA tests and head magnetic resonance imaging (MRI). Meanwhile, a dramatic decrease of immune cells and immunoglobulin was detected in the occurrence of DLBCL. He received therapy based on SCCCG-NHL-2017 protocol immediately after the diagnosis. CONCLUSIONS: We present the first retrospective report of four cases of non-Hodgkin lymphoma (NHL) secondary to ALL between 1990 and 2022. The pathogenesis of secondary DLBCL may be related to infection, immunodeficiency, genetic susceptibility, and treatment. Thus, the detection of EBV DNA during the full course of ALL therapy and genetic tests were needed in the occurrence of secondary DLBCL. Given to the rare rate and insufficient treatment experience, longer follow-up and enough sample size are needed.

Optimized optical system with a 1.65 m wide-field corrector for the 6.5 m high-performance MUltiplexed Survey Telescope.

The development of modern large-scale spectroscopic survey telescopes responds to the urgent demand for spectral information in astronomical research. Tsinghua University has previously proposed a 6.5 m MUltiplexed Survey Telescope consisting of a Ritchey-Chretien configuration and a 1.8 m multi-element wide-field corrector, achieving excellent performance and world-leading survey efficiency. However, an optimized 1.65 m multi-element corrector with five lenses is proposed to overcome the constraints on glass uniformity and verification in fabrication of the previous corrector design. It maintains outstanding image quality, with the 80% enclosed energy diameter not more than 0.559 arcsec within 3° FoV over up to a 55° zenith angle. The optimized optical system does not revise the working mode of the ADC or the curvature of the primary mirror while ensuring the reasonability and accuracy of manufacturing of large corrector elements. It provides a more feasible reference optical design for the MUltiplexed Survey Telescope in subsequent iterations and communications with manufacturers.

Ac2-26 reduced the liver injury after cardiopulmonary bypass in rats via AKT1/GSK3ß/eNOS pathway.

OBJECTIVE: About 10% of patients after cardiopulmonary bypass (CPB) would undergo acute liver injury, which aggravated the mortality of patients. Ac2-26 has been demonstrated to ameliorate organic injury by inhibiting inflammation. The present study aims to evaluate the effect and mechanism of Ac2-26 on acute liver injury after CPB. METHODS: A total of 32 SD rats were randomized into sham, CPB, Ac, and Ac/AKT1 groups. The rats only received anesthesia, and rats in other groups received CPB. The rats in Ac/AKT1 were pre-injected with the shRNA to interfere with the expression of AKT1. The rats in CPB were injected with saline, and rats in Ac and Ac/AKT1 groups were injected with Ac2-26. After 12 h of CPB, all the rats were sacrificed and the peripheral blood and liver samples were collected to analyze. The inflammatory factors in serum and liver were detected. The liver function was tested, and the pathological injury of liver tissue was evaluated. RESULTS: Compared with the sham group, the inflammatory factors, liver function, and pathological injury were worsened after CPB. Compared with the CPB group, the Ac2-26 significantly decreased the pro-inflammatory factors and increased the anti-inflammatory factor, improved liver function, and ameliorated the pathological injury. All the therapeutic effects of Ac2-26 were notably attenuated by the shRNA of AKT1. The Ac2-26 increased the GSK3ß and eNOS, and this promotion was inhibited by the shRNA. CONCLUSION: The Ac2-26 significantly treated the liver injury, inhibited inflammation, and improved liver function. The effect of Ac2-26 on liver injury induced by CPB was partly associated with the promotion of AKT1/GSK3ß/eNOS.

Population differentiation and dynamics of five pioneer species of Gaultheria from the secondary forests in subtropical China.

BACKGROUND: The influence of native secondary succession associated with anthropogenic disturbance on the biodiversity of the forests in subtropical China remains uncertain. In particular, the evolutionary response of small understory shrubs, particularly pioneer species inhabiting continuously disturbed habitats, to topographic heterogeneity and climate change is poorly understood. This study aimed to address this knowledge gap by focusing on the Gaultheria crenulata group, a clade of small pioneer shrubs in subtropical China. RESULTS: We examined the genetic structure and demographic history of all five species of the G. crenulata group with two maternally inherited chloroplast DNA (cpDNA) fragments and two biparentally inherited low-copy nuclear genes (LCG) over 89 natural populations. We found that the genetic differentiation of this group was influenced by the geomorphological boundary between different regions of China in association with Quaternary climatic events. Despite low overall genetic diversity, we observed an isolation-by-distance (IBD) pattern at a regional scale, rather than isolation-by-environment (IBE), which was attributed to ongoing human disturbance in the region. CONCLUSION: Our findings suggest that the genetic structure of the G. crenulata group reflects the interplay of geological topography, historical climates, and anthropogenic disturbance during the Pliocene-Pleistocene-Holocene periods in subtropical China. The observed IBD pattern, particularly prominent in western China, highlights the role of limited dispersal and gene flow, possibly influenced by physical barriers or decreased connectivity over geographic distance. Furthermore, the east-to-west trend of gene flow, potentially facilitated by the East Asian monsoon system, underscores the complex interplay of biotic and abiotic factors shaping the genetic dynamics of pioneer species in subtropical China's secondary forests. These findings can be used to assess the impact of environmental changes on the adaptation and persistence of biodiversity in subtropical forest ecosystems.

A bispecific antibody exhibits broad neutralization against SARS-CoV-2 Omicron variants XBB.1.16, BQ.1.1 and sarbecoviruses.

The Omicron subvariants BQ.1.1, XBB.1.5, and XBB.1.16 of SARS-CoV-2 are known for their adeptness at evading immune responses. Here, we isolate a neutralizing antibody, 7F3, with the capacity to neutralize all tested SARS-CoV-2 variants, including BQ.1.1, XBB.1.5, and XBB.1.16. 7F3 targets the receptor-binding motif (RBM) region and exhibits broad binding to a panel of 37 RBD mutant proteins. We develop the IgG-like bispecific antibody G7-Fc using 7F3 and the cross-neutralizing antibody GW01. G7-Fc demonstrates robust neutralizing activity against all 28 tested SARS-CoV-2 variants and sarbecoviruses, providing potent prophylaxis and therapeutic efficacy against XBB.1 infection in both K18-ACE and BALB/c female mice. Cryo-EM structure analysis of the G7-Fc in complex with the Omicron XBB spike (S) trimer reveals a trimer-dimer conformation, with G7-Fc synergistically targeting two distinct RBD epitopes and blocking ACE2 binding. Comparative analysis of 7F3 and LY-CoV1404 epitopes highlights a distinct and highly conserved epitope in the RBM region bound by 7F3, facilitating neutralization of the immune-evasive Omicron variant XBB.1.16. G7-Fc holds promise as a potential prophylactic countermeasure against SARS-CoV-2, particularly against circulating and emerging variants.

Development of a predictive nomogram for intermediate-risk differentiated thyroid cancer patients after fixed 3.7GBq (100mCi) radioiodine remnant ablation.

Objectives: The objective of this study was to develop a predictive nomogram for intermediate-risk differentiated thyroid cancer (DTC) patients after fixed 3.7GBq (100mCi) radioiodine remnant ablation (RRA). Methods: Data from 265 patients who underwent total thyroidectomy with central lymph node dissection (CND) and received RRA treatment at a single institution between January 2018 and March 2023 were analyzed. Patients with certain exclusion criteria were excluded. Univariate and multivariate logistic regression analyses were performed to identify risk factors for a non-excellent response (non-ER) to RRA. A nomogram was developed based on the risk factors, and its performance was validated using the Bootstrap method with 1,000 resamplings. A web-based dynamic calculator was developed for convenient application of the nomogram. Results: The study included 265 patients with intermediate-risk DTC. Significant differences were found between the ER group and the non-ER group in terms of CLNM>5, Hashimoto's thyroiditis, sTg level, TgAb level (P < 0.05). CLNM>5 and sTg level were identified as independent risk factors for non-ER in multivariate analysis. The nomogram showed high accuracy, with an area under the curve (AUC) of 0.833 (95% CI = 0.770-0.895). The nomogram's predicted probabilities aligned closely with actual clinical outcomes. Conclusions: This study developed a predictive nomogram for intermediate-risk DTC patients after fixed 3.7GBq (100mCi) RRA. The nomogram incorporates CLNM>5 and sTg levels as risk factors for a non-ER response to RRA. The nomogram and web-based calculator can assist in treatment decision-making and improve the precision of prognosis information. Further research and validation are needed.

Develop a bone mineral density T-score distribution nomograms based on osteoporosis risk factors for middle-aged and older adults.

PURPOSE: This study aimed to understand how age, health status, and lifestyle impact bone mineral density (BMD) in middle-aged and older adults, focusing on predicting osteoporosis risk. METHODS: This study included 2836 participants aged 50-88 from the Health Improvement Program of Bone (HOPE) conducted from 2021 to 2023. We used logistic regression to make a prediction tool. Then checked its accuracy and reliability using receiver operating characteristic (ROC) and calibration curves. RESULTS: Factors like age, body weight, prior fractures, and smoking were independently found to affect BMD T-score distribution in men. In women, age and body weight were identified as independent factors influencing BMD T-score distribution. A nomogram was created to visually illustrate these predictive relationships. CONCLUSIONS: The nomogram proved highly accurate in identifying men aged 50 and above and postmenopausal women based on their BMD T-score distribution, improving clinical decision-making and patient care in osteoporosis evaluation and treatment.

Exploring the novel benefits of leucine: Protecting nitrite-induced liver damage in sub-adult grass carp (Ctenopharyngodon idella) through regulating mitochondria quality control.

Leucine is an essential amino acid for fish. The ability of leucine to resist stress in fish has not been reported. Nitrite is a common pollutant in the aquatic environment. Therefore, we investigated the effects of dietary leucine on growth performance and nitrite-induced liver damage, mitochondrial dysfunction, autophagy, and apoptosis for sub-adult grass carp. A total of 450 grass carp (615.91 ± 1.15 g) were selected and randomly placed into 18 net cages. The leucine contents of the six diets were 2.91, 5.90, 8.92, 11.91, 14.93, and 17.92 g/kg, respectively. After a 9-week feeding trial, the nitrite exposure experiment was set up for 96 h. These results indicated that dietary leucine significantly promoted FW, WG, PWG, and SGR of sub-adult grass carp (P < 0.05). Appropriate levels of dietary leucine (11.91-17.92 g/kg) decreased the activities of serum parameters (glucose, cortisol, and methemoglobin contents, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactate dehydrogenase), the contents of reactive oxygen species (ROS), nitric oxide (NO) and peroxynitrite (ONOO-). In addition, appropriate levels of dietary leucine (11.91-17.92 g/kg) increased the mRNA levels of mitochondrial biogenesis genes (PGC-1α, Nrf1/2, TFAM), fusion-related genes (Opa1, Mfn1/2) (P < 0.05), and decreased the mRNA levels of caspase 3, caspase 8, caspase 9, fission-related gene (Drp1), mitophagy-related genes (Pink1, Parkin) and autophagy-related genes (Beclin1, Ulk1, Atg5, Atg7, Atg12) (P < 0.05). Appropriate levels of dietary leucine (8.92-17.92 g/kg) also increased the protein levels of AMP-activated protein kinase (AMPK), prostacyclin (p62) and decreased the protein levels of protein light chain 3 (LC3), E3 ubiquitin ligase (Parkin), and Cytochrome c (Cytc). Appropriate levels of leucine (8.92-17.92 g/kg) could promote growth performance and alleviate nitrite-induced mitochondrial dysfunction, autophagy, apoptosis for sub-adult grass carp. Based on quadratic regression analysis of PWG and serum GPT activity, dietary leucine requirements of sub-adult grass carp were recommended to be 12.47 g/kg diet and 12.55 g/kg diet, respectively.

Analysis of stage parameters of low-temperature oxidation of water-soaked coal based on kinetic principles.

Mine fires caused by spontaneous coal combustion are major disasters in coal mines. The staged oxidation kinetic parameters of various coal samples at oxygen concentrations of 21 %, 15 %, 10 %, 5 %, and 3 % were analyzed using a programmed temperature testing system. Herein, the temperature increase rate of coal, the temperature difference between the furnace and coal, and the oxygen consumption characteristics were obtained. Based on the amount of CO produced and the temperature sensitivity coefficient, three characteristic temperatures and four stages of low-temperature oxidation (LTO) were identified. The results showed that at a critical temperature (TC), the amount of CO gas released from the coal samples increased with increasing oxygen concentration, and the difference in the oxygen consumption rate increased. After the limit temperature (Tu), the amount of CO gas increased steadily, and the increase in the oxygen consumption rate stagnated. CO production, the maximum heating rate, and the maximum heat release rate were positively correlated with the oxygen concentration. As the oxygen concentration increased, the activation energy during the oxygen absorption stage gradually decreased. The average reaction enthalpy (ΔH) of pre-oxidized water-immersed coal was 19.37 kJ/kg greater than that of raw coal. The equation for the conservation of energy of the coal oxidation warming process was normalized. The theoretical values of the awakening stage and the stable stage were τν and τν (1-B), respectively. When B was >1, pre-oxidized water-immersed coal at a low oxygen concentration was prone to crossover points during the oxygen absorption stage, which increased the risk of coal spontaneous combustion (CSC). The research results could provide a theoretical basis for the staged control of the spontaneous combustion of water-immersed coal in goaf areas.

Clinical application of dual-layer spectral CT multi-parameter feature to predict microvascular invasion in hepatocellular carcinoma.

OBJECTIVE: This study aimed to investigate the feasibility of using dual-layer spectral CT multi-parameter feature to predict microvascular invasion of hepatocellular carcinoma. METHODS: This retrospective study enrolled 50 HCC patients who underwent multiphase contrast-enhanced spectral CT studies preoperatively. Combined clinical data, radiological features with spectral CT quantitative parameter were constructed to predict MVI. ROC was applied to identify potential predictors of MVI. The CT values obtained by simulating the conventional CT scans with 70 keV images were compared with those obtained with 40 keV images. RESULTS: 50 hepatocellular carcinomas were detected with 30 lesions (Group A) with microvascular invasion and 20 (Group B) without. There were significant differences in AFP,tumer size, IC, NIC,slope and effective atomic number in AP and ICrr in VP between Group A ((1000(10.875,1000),4.360±0.3105, 1.7750 (1.5350,1.8825) mg/ml, 0.1785 (0.1621,0.2124), 2.0362±0.2108,8.0960±0.1043,0.2830±0.0777) and Group B (4.750(3.325,20.425),3.190±0.2979,1.4700 (1.4500,1.5775) mg/ml, 0.1441 (0.1373,0.1490),1.8601±0.1595, 7.8105±0.7830 and 0.2228±0.0612) (all p < 0.05). Using 0.1586 as the threshold for NIC, one could obtain an area-under-curve (AUC) of 0.875 in ROC to differentiate between tumours with and without microvascular invasion. AUC was 0.625 with CT value at 70 keV and improved to 0.843 at 40 keV. CONCLUSION: Dual-layer spectral CT provides additional quantitative parameters than conventional CT to enhance the differentiation between hepatocellular carcinoma with and without microvascular invasion. Especially, the normalized iodine concentration (NIC) in arterial phase has the greatest potential application value in determining whether microvascular invasion exists, and can offer an important reference for clinical treatment plan and prognosis assessment.

Protective effects of the secondary metabolites from Quercus salicina Blume against gentamicin-induced nephrotoxicity in zebrafish (Danio rerio) model.

To reveal the protective effect on the nephrotoxicity of Quercus salicina Blume(QS), a traditional medicine for the treatment of urolithiasis, the 50 % ethanol extract from the branches and leaves of QS was chemically studied by systematic solvent extraction and HPLC chromatography. Two phenolic acids and three flavonoids were identified by nuclear magnetic resonance spectroscopy, namely Ferulic acid (1), p-Hydroxycinnamic acid (2), Hesperidin (3), Formononetin (4), and Quercetin (5). At the same time, the gentamicin-induced nephrotoxicity of zebrafish was used as a model for the first time. The antioxidant activity of these derivatives with good antioxidant activity screened from free radical scavenging experiments in vitro (DPPH and ABTS) was evaluated in vivo, including protein levels (LPO, NO, GSH, and SOD), kidney injury factor (KIM-1), zebrafish kidney pathology and real-time PCR. The results showed that metabolites 1, 3, and 5 had strong antioxidant activity, and oxidative stress in renal tissue was significantly reduced; KIM-1, TNF-α, and IL-6 mRNA expression in a dose-dependent manner, which preliminarily revealed the protective effect of the secondary metabolites of QS on nephrotoxicity, and preliminarily discussed the structure-activity relationship. This study provides an experimental basis for further exploring the mechanism of QS in the kidney.

Discovery of a Double-Stapled Short Peptide as a Long-Acting HIV-1 Inactivator with Potential for Oral Bioavailability.

Different from most antiretroviral drugs that act as passive defenders to inhibit HIV-1 replication inside the host cell, virus inactivators can attack and inactivate HIV-1 virions without relying on their replication cycle. Herein, we describe the discovery of a hydrocarbon double-stapled helix peptide, termed D26. D26 is based on the HIV-1 gp41 protein lentiviral lytic peptide-3 motif (LLP3) sequence, which can efficiently inhibit HIV-1 infection and inactivate cell-free HIV-1 virions. It was noted that D26 was highly resistant to proteolytic degradation and exhibited a remarkably extended in vivo elimination half-life. Additionally, relative to its linear, nonstapled version, D26 exhibited much higher exposure in sanctuary sites for HIV-1. Amazingly, this lead compound also demonstrated detectable oral absorption. Thus, it can be concluded that D26 is a promising candidate for further development as a long-acting, orally applicable HIV-1 inactivator for the treatment of HIV-1 infection.

Carbon Dot-Loaded Apoptotic Vesicles Improve the Liver Kupffer Cell-Mediated Antibacterial Effect to Synergistically Alleviate Sepsis.

Sepsis is a lethal systemic inflammatory disease against infection that lacks effective therapeutic approaches. Liver resident macrophage Kupffer cell (KC)-initiated bacterial clearance is crucial for the host to defend against infection. However, it remains unclear whether this process also governs the antibacterial therapy of sepsis that would be used to improve therapeutic outcomes. Here, we found that copper-doped carbon dots (Cu-CDs) exhibited superior antibacterial capabilities in vitro but displayed limited therapeutic effects in septic mice due to their limited ability to target the liver and restore KC antimicrobial capacity. Thus, we developed a composite nanodrug of copper-doped carbon dot-loaded apoVs (CC-apoVs) that combined the antibacterial ability of Cu-CDs and liver KC targeting features of apoV. Moreover, intravenous injection of CC-apoVs markedly alleviated the systemic infection and decreased the mortality of septic mice compared to Cu-CD and apoV infusion alone. Mechanistically, CC-apoV injection rescued impaired liver KCs during sepsis and enhanced their ability to capture and kill bloodborne bacteria. In addition, apoV-promoted macrophage killing of bacteria could be blocked by the inhibition of small GTPase Rab5. This study reveals a liver KC-targeted therapeutic strategy for sepsis and provides a nanodrug CC-apoV to improve the host antibacterial defense and amplify the therapeutic effect of the nanodrug.

[Spatial and Temporal Distribution of Antibiotic Resistance Genes in Different River Sediments in Typical Cities: A Case Study of Shijiazhuang].

Rivers are important reservoirs of antibiotic resistance genes (ARGs). However, most current studies have focused on the temporal and spatial distribution, and data on the differences in the species and abundance of ARGs between urban and rural rivers is still lacking for certain areas. In view of this, two rural rivers and three urban rivers were selected in Shijiazhuang City. In both December 2020 and April 2021, sediments were collected at 15 sampling sites. Metagenomic sequencing technology was used to compare the differences in temporal-spatial variation for ARGs in sediments. The results showed that:① 162 and 79 ARGs were detected in urban (4 776 ±4 452) and rural rivers (1 043 ±632), respectively. The abundance and species of ARGs in urban rivers were higher than those in rural rivers. ② The relative abundances of sulfonamide (SAs,27 %), aminoglycoside (AGs,26 %), and multidrug (MDs,15 %) ARGs had the highest abundance in urban rivers, whereas the relative abundance of MDs ARGs was highest in rural rivers (65 %). On the whole, the complexity of ARGs in urban rivers was higher than that in rural rivers. ③ There was a significant positive correlation between SAs, AGs, MDs, tetracycline, phenicol, macrolides-lincosamids-streptogramins (MLS), ß-lactams, and diaminopyrimidine ARGs in urban rivers (P < 0.01); however, there was a significant negative correlation between glycopeptide ARGs and all types of ARGs (P < 0.05 and P < 0.01). There was a significant positive correlation between MDs and SAs ARGs in rural rivers (P < 0.05), but there was a significant negative correlation between amino aminocoumarin, peptide, rifamycin, and fosfomycin ARGs (P < 0.05 and P < 0.01). ④ For the temporal variation in urban rivers, 162 ARGs (4 776 ±4 452) and 148 ARGs (5 673 ±5 626) were detected in December and April, respectively. For the temporal variation in rural rivers, 79 species (1 043 ±632) and 46 species (467 ±183) were detected in December and April, respectively. ⑤ RDA analysis results showed that the spatial-temporal distributions of ARGs in urban and rural rivers were different. Correlation analysis showed that the ARGs in urban rivers were significantly correlated with the number of industrial enterprises, whereas the ARGs in rural rivers were significantly correlated with the output value of animal husbandry. In general, this study identified the main influencing factors for ARGs in different rivers and provided data support for ARGs risk management in different rivers.

Dual-target inhibitors of colchicine binding site for cancer treatment.

Colchicine binding site inhibitors (CBSIs) have attracted much attention due to their antitumor efficacies and the advantages of inhibiting angiogenesis and overcoming multidrug resistance. However, no CBSI has been currently approved for cancer treatment due to the insufficient efficacies, serious toxicities and poor pharmacokinetic properties. Design of dual-target inhibitors is becoming a potential strategy for cancer treatment to improve anticancer efficacy, decrease adverse events and overcome drug resistance. Therefore, we reviewed dual-target inhibitors of colchicine binding site (CBS), summarized the design strategies and the biological activities of these dual-target inhibitors, expecting to provide inspiration for developing novel dual inhibitors based on CBS.

Kaempferol from Alpinia officinarum hance induces G2/M cell cycle arrest in hepatocellular carcinoma cells by regulating the ATM/CHEK2/KNL1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Alpinia officinarum Hance (A. officinarum), a perennial herb known for its medicinal properties, has been used to treat various ailments, such as stomach pain, abdominal pain, emesis, and digestive system cancers. A. officinarum is extensively cultivated in the Qiongzhong and Baisha regions of Hainan, and it holds substantial therapeutic value for the local Li people of Hainan. Kaempferol, a flavonoid derived from A. officinarum, has demonstrated anticancer properties in various experimental and biological studies. Nevertheless, the precise mechanisms through which it exerts its anti-hepatocellular carcinoma (HCC) effects remain to be comprehensively delineated. AIM OF THE STUDY: This investigation aims to elucidate the anti-HCC effects of kaempferol derived from A. officinarum and to delve into its underlying mechanistic pathways. MATERIALS AND METHODS: Using ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) to identify active compounds in A. officinarum. HCCLM3 and Huh7 cells were used to study the anti-HCC effect of kaempferol from A. officinarum. The cytotoxicity and proliferation of kaempferol and A. officinarum were measured using CCK-8 and EDU staining. Wound-healing assays and three-dimensional tumor spheroid models were further used to evaluate migration and the anti-HCC activity of kaempferol. The cell cycle and apoptosis were evaluated by flow cytometry. Western blot and qRT-PCR were used to detect the expression of proteins and genes associated with the cell cycle checkpoints. Finally, bioinformatics was used to analyze the relationship between the differential expression of core targets in the ATM/CHEK2/KNL1 pathway and a poor prognosis in clinical HCC samples. RESULTS: UPLC-MS/MS was employed to detect five active compounds in A. officinarum, such as kaempferol. The CCK-8 and EDU assays showed that kaempferol and A. officinarum significantly inhibited the proliferation of HCC cells. A wound-healing assay revealed that kaempferol remarkably inhibited the migration of HCC cells. Kaempferol significantly suppressed the growth of tumor spheroids. In addition, kaempferol markedly induced G2/M arrest and promoted apoptosis of HCC cells. Mechanically, kaempferol significantly reduced the protein and mRNA expression levels of ATM, CHEK2, CDC25C, CDK1, CCNB1, MPS1, KNL1, and Bub1. Additionally, the combination of kaempferol and the ATM inhibitor KU55933 had a more significant anti-HCC effect. The results of bioinformatics showed that ATM, CHEK2, CDC25C, CDK1, and KNL1 were highly expressed in patients with HCC and cancer tissues, indicating that these genes have certain value in the clinical diagnosis of HCC. CONCLUSIONS: Collectively, our results revealed that kaempferol from A. officinarum inhibits the cell cycle by regulating the ATM/CHEK2/KNL1 pathway in HCC cells. In summary, our research presents an innovative supplementary strategy for HCC treatment.

Effects of miR-29c on proliferation and adipogenic differentiation of porcine bone marrow mesenchymal stromal cells.

microRNAs (miRNAs), a subclass of noncoding short RNAs, direct cells fate decisions that are important for cell proliferation and cell lineage decisions. Adipogenic differentiation contributes greatly to the development of white adipose tissue, involving of highly organized regulation by miRNAs. In the present study, we screened and identified 78 differently expressed miRNAs of porcine BMSCs during adipogenic differentiation. Of which, the role of miR-29c in regulating the proliferation and adipogenic differentiation was proved and detailed. Specifically, over-expression miR-29c inhibits the proliferation and adipogenic differentiation of BMSCs, which were reversed upon miR-29c inhibitor. Interference of IGF1 inhibits the proliferation and adipogenic differentiation of BMSCs. Mechanistically, miR-29c regulates the proliferation and adipogenic differentiation of BMSCs by targeting IGF1 and further regulating the MAPK pathway and the PI3K-AKT-mTOR pathway, respectively. In conclusion, we highlight the important role of miR-29c in regulating proliferation and adipogenic differentiation of BMSCs.

[Research status and rapid detection methods of antibiotic residues in agricultural products]. / å†œäº§å“æŠ—ç”Ÿç´ æ®‹ç•™çŽ°çŠ¶åŠå¿«é€Ÿæ£€æµ‹æ–¹æ³•ç ”ç©¶è¿›å±•.

Antibiotics are widely utilized in agriculture for the prevention and treatment of animal diseases. How-ever, the abuse and overuse of antibiotics progressively increase the risks of antibiotic residues and antibiotic resis-tance. The bioaccumulation and biomagnification of antibiotics through food chains will negatively affect ecological safety, and finally threaten human health. There are many shortages of traditional antibiotic detection techniques, such as complex procedures, complicated operation and time consuming, and thus are difficult to meet the demand of instant, efficient and accurate on-site detection. Therefore, it is crucial to develop rapid detection techniques of antibiotics to manage the application of antibiotics in agriculture. We reviewed the utilization, and management of antibiotics in animal husbandry, residual characteristics, and potential hazards of antibiotics in agricultural products, summarized the advancements in rapid detection techniques of antibiotics in agricultural products over the past five years, compared the advantages and disadvantages of different rapid detection techniques, and prospected the future development in this area. This review would provide a valuable reference to the control and point-of-care test of antibiotics in agricultural products.

Establishment of homotrimer collagen type I signature and its association with clinical manifestation and tertiary lymphoid structures formation in liver cancer.

Background: collagen type I is a fundamental composition of extracellular matrix. Typically it exists in the form of a heterotrimer, consisting of two α1 chains encoded by COL1A1 and one α2 chain encoded by COL1A2. However, in cancer a homotrimeric form of collagen type I comprises three α1 chains encoded by COL1A1 was founded. There is still a lack of transcriptional and histologic methods for detecting homotrimeric collagen type I. Furthermore, a comprehensive analysis of the pan-cancer distribution pattern and clinical relevance of homotrimeric collagen type I is conspicuously absent. Method: Using transcriptional and immunoflourance method, we established homocol signature, which is able to transcriptionally and histologically detect homotrimeric collagen type I. We investigated the diagnostic and prognostic potential of homocol as a novel cancer biomarker in a pan-cancer cohort. Furthermore, we assessed its association with clinical manifestations in a liver cancer cohort undergoing treatment at our institute. Result: Homotrimer Collagen Type I is predominantly expressed by cancer cells and is linked to several critical cancer hallmarks, particularly inflammatory response and proliferation. Survival analyses have indicated that a high Homocol expression is correlated with poor outcomes in most types of cancer studied. In terms of cancer detection, Homocol demonstrated strong performance in Receiver Operating Characteristic (ROC) analysis, with an Area Under Curve (AUC) of 0.83 for pan-cancer detection and between 0.72 and 0.99 for individual cancers.In cohorts undergoing PD1 treatment, we noted a higher presence of Homocol in the response group. In a Hepatocellular Carcinoma (HCC) clinical set, high Homocol expression was associated with an increased formation of intra-tumor tertiary lymphoid structures (TLS), larger tumor sizes, more advanced Barcelona Clinic Liver Cancer (BCLC) stages, higher microvascular invasion (MVI) grades, absence of a capsule, and an enriched para-tumor collagen presence. Conclusion: our research has led to the development of a novel gene signature that facilitates the detection of Homotrimer Collagen Type I. This may greatly assist efforts in cancer detection, prognosis, treatment response prediction, and further research into Homotrimer Collagen Type I.

Trends in cardiovascular health among US adults by glycemic status based on Life's Essential 8.

OBJECTIVE: We aimed to assess the secular trends in cardiovascular health (CVH) among U.S. adults with different glycemic statuses based on the Life's Essential 8 (LE8). METHODS: This cross-sectional study used nationally representative data from 6 cycles of the National Health and Nutrition Examination Surveys between 2007 and 2018. Survey-weighted linear models were used to assess time trends in LE8 scores. Stratified analyses and sensitivity analyses were conducted to validate the stability of the results. RESULTS: A total of 23,616 participants were included in this study. From 2007 to 2018, there was no significant improvement in overall CVH and the proportion of ideal CVH among participants with diabetes and prediabetes. We observed an opposite trend between health behavior and health factors in the diabetes group, mainly in increasing physical activity scores and sleep scores (P for trend<0.001), and declining BMI scores [difference, -6.81 (95% CI, -12.82 to -0.80)] and blood glucose scores [difference, -6.41 (95% CI, -9.86 to -2.96)]. Dietary health remained at a consistently low level among participants with different glycemic status. The blood lipid scores in the prediabetes group improved but were still at a lower level than other groups. Education/income differences persist in the CVH of participants with diabetes or prediabetes, especially in health behavior factors. Sensitivity analyses of the absolute difference and change in proportion showed a consistent trend. CONCLUSIONS: Trends in CVH among participants with diabetes or prediabetes were suboptimal from 2007 to 2018, with persistent education/income disparities.