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Abstract Background To date, the relationship between the Transesophageal Echocardiography (TEE) monitoring indicator tricuspid annular plane systolic excursion (TAPSE) and the incidence of postoperative acute kidney injury (AKI) in Coronary Artery Bypass Grafting(CABG) patients remains unknown. The main objective of this study was to explore the relationship between the TAPSE and the incidence of AKI in CABG patients. Methods This was a multicenter prospective cohort study was conducted between September 2021 and July 2022. Among 266 patients aged at least 18 years who underwent elective CABG, 140 were included. Results We measured TAPSE via M-mode TEE via the mid-esophageal (ME) right ventricle(RV) inflow-outflow view (60°). All echocardiographic measurements were performed three separate times at each time point: T0 (before the start of CABG), T2 (approximately 5 ∼ 10 min after neutralization of protamine) and T3 (before leaving the operating room), and then averaged. Serum creatinine was measured 1 day before and within 7 days after CABG. There was no statistically significant association between the TEE-monitoring indicator TAPSE and the incidence of postoperative AKI in patients who underwent CABG. Conclusions The TAPSE was not significantly correlated with postoperative AKI incidence and could not predict the early occurrence of postoperative AKI in CABG patients. TEE needs more evaluation for clinical efficacy of predicting the early occurrence of postoperative AKI in isolated CABG.

Abstract Trichosanthes truncata C. B. Clarke, an important medicinal plant, is a dioecious plant belonging to the Cucurbitaceae family. This study presents a chromosomal-level reference genome assembly for T. truncata. Through the integration of PacBio high-fidelity sequencing and high-throughput chromosome conformation capture technology, a final genome sequence of 637.41 Mb was assembled, with an N50 of 57.24 Mb and consisting of 11 pseudochromosomes. Additionally, 97.21 Mb of repetitive sequences and 36,172 protein-coding genes were annotated. This high-quality genome assembly is of utmost significance for studying the molecular mechanisms underlying the biosynthesis of bioactive compounds. Furthermore, this study provided valuable insights into plant comparative genomics research.

Objective: To investigate the antioxidant activity of fermented tartaty buckwheat extract of Pleurotus eryngii in vitro as well as its protective effect on alcohol-induced liver and gastric mucosa injury in vivo. Methods: The study involved determining the contents of functional components in fermented tartary buckwheat extract and observing its antioxidant capacity. Mice models of chronic alcoholic liver and gastric mucosa injury were established using Lieber-DeCarli liquid feed. The protective effects of fermented tartary buckwheat extract at low and high doses (1.5 g/kg B.W., 3.0 g/kg B.W.) were investigated for both liver and gastric mucosa injury. Results: The extract of fermented buckwheat with Pleurotus eryngii contained more antioxidant components, the contents of polyphenols, flavonoids and triterpenes were 11.40±0.32 mgGAE/g DW, 17.19±0.30 mg RE/g DW and 7.59±0.24 mg/g, respectively. The contents of rutin and quercetin were as follows: 13.55±0.05 and 0.665±0.01 mg/g. The iron reducing antioxidant capacity and DPPH and ABTS+ free radical scavenging efficiency of Tartary buckwheat extract were 16.66±0.65, 33.49±1.26 and 15.68±1.17 μmol Trolox/g DW, respectively. Compared with the model group, both high-dose and low-dose groups significantly reduced malondialdehyde (P

IntroductionThis study was to analyze the dynamics of tissue damage and inflammatory response markers perioperatively and whether these differ between robotic laparoscopy and conventional laparoscopy in early endometrial cancer.MethodsIn a randomized controlled trial conducted at SHANGHAI FIRST MATERNITY and INFANT HOSPITAL, eighty women with early-stage, low-risk endometrial cancer were randomly assigned to receive either robotic or conventional laparoscopy. Blood samples were collected at admission, immediately before surgery, 2 h after surgery, 24 h after surgery, 48 h after surgery, and 1 week after surgery. The samples were analyzed for various biomarkers associated with inflammatory processes and tissue damage. These included high-sensitivity C-reactive protein (hs-CRP), white blood cell count (WBC), platelet count, interleukin-6 (IL-6), cortisol, creatine kinase (CK), and tumor necrosis factor-alpha (TNF-α). These markers provide insights into the underlying physiological responses and potential tissue-level changes within the study participants.ResultsThere was no significant difference in clinical and preoperative data between two groups. The results showed that the patients who underwent robotic laparoscopy had a longer pre-surgical time compared to the conventional laparoscopy group. However, the robotic group had shorter operating times, quicker vaginal cuff closures, and lower estimated blood loss compared to the conventional laparoscopy group. The hospital stays, Visual Analog Scale (VAS) score and drainage volume on the first day after operation were lower in robotic group compared to conventional laparoscopy group. hs-CRP, WBC, IL-6 and cortisol were significantly lower in the robotic group, though the differences were transient.DiscussionThis study demonstrated that robotic laparoscopy, used in early endometrial cancer treatment, leads to a reduced inflammatory response, less tissue damage, and lower stress levels, as evidenced by decreased levels of hs-CRP, IL-6, and cortisol, compared to conventional laparoscopy. These findings suggest that robot- laparoscopy may facilitate a quicker recovery and improve patient-reported outcomes.

Abstract Uniaxial compression tests and cyclic loading acoustic emission tests were conducted on 20%, 40%, 60%, 80%, dry and saturated muddy sandstone by using a creep impact loading system to investigate the mechanical properties and acoustic emission characteristics of soft rocks with different water contents under dynamic disturbance. The mechanical properties and acoustic emission characteristics of muddy sandstones at different water contents were analysed. Results of experimental studies show that water is a key factor in the mechanical properties of rocks, softening them, increasing their porosity, reducing their brittleness and increasing their plasticity. Under uniaxial compression, the macroscopic damage characteristics of the muddy sandstone change from mono-bevel shear damage and ‘X’ type conjugate bevel shear damage to a roadway bottom-drum type damage as the water content increases. Dynamic perturbation has a strengthening effect on the mechanical properties of samples with 60% and less water content, and a weakening effect on samples with 80% and more water content, but the weakening effect is not obvious. Macroscopic damage characteristics of dry samples remain unchanged, water samples from shear damage and tensile–shear composite damage gradually transformed into cleavage damage, until saturation transformation monoclinic shear damage. The evolution of acoustic emission energy and event number is mainly divided into four stages: loading stage (I), dynamic loading stage (II), yield failure stage (III), and post-peak stage (IV), the acoustic emission characteristics of the stages were different for different water contents. The characteristic value of acoustic emission key point frequency gradually decreases, and the damage degree of the specimen increases, corresponding to low water content—high main frequency—low damage and high water content—low main frequency—high damage.

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a rare disease without standardized treatment modalities. Daratumumab is a human IgG monoclonal anti-CD38 antibody that has been demonstrated to be highly effective and safe in the treatment of PGNMID. This article reports a 66-year-old female who suffered from edema in both lower limbs and face for 6 years with mild proteinuria and hypoproteinemia. Renal biopsy displayed eight glomeruli, among which two presented with glomerulosclerosis, and the remaining six exhibited moderate diffuse hyperplasia of glomerular mesangial cells and stroma with endothelial cell proliferation. Immunofluorescence microscopy revealed lumpy and diffuse deposits of C3, C1q, IgG, and κ light chain in the glomerular mesangium, with strongly positive staining for IgG3 and varying degrees of weak to negative staining for IgG1, IgG2, IgG4, and λ light chain. Additionally, ultrastructural analysis unveiled that the glomerular basement membrane was segmentally thickened, accompanied by diffuse pedicle fusion, segmental tethered insertion, subendothelial deposits, and electron-dense material in tethered areas. The patient received a total dose of 800 mg of daratumumab (400 mg daily for two consecutive days), as well as daily prednisone (25 mg) and valsartan (80 mg), for treatment and achieved complete remission after three-month follow-up. This case represents an early attempt to treat PGNMID with low-dose daratumumab but requires long-term follow-up.

Aiming at the problem of multi-point layout planning of a multi-energy power system, the output characteristics of a multi-energy power system composed of wind power generation, photovoltaic power generation, hydropower generation, traditional thermal power generation and solar thermal power generation are comprehensively analyzed. Combining power optimization planning with complex adaptive system theory, a multi-point layout planning model of multi-energy sources based on complex adaptive system theory is proposed. The model takes the minimum construction step size of each new energy source as the agent. Through the interaction between the agents and the accumulation of experience, the behavior rules are constantly changed, the installed positions of various types of power sources are adjusted, and the optimal layout scheme of various power capacities of each node is obtained. Moreover, an agent modeling method based on a simple rule emerging complex phenomena is proposed, which reveals the core idea of complex adaptive system theory-adaptability makes complexity. Taking an actual power grid in a certain region of China as an example, it is verified that the proposed method has a significant effect on improving the consumption of new energy, and has certain guiding significance for the actual engineering construction.

Abstract Gastric cancer remains a leading cause of cancer-related death worldwide, largely due to inadequate screening methods, late diagnosis, and limited treatment options. Liquid biopsy has emerged as a promising non-invasive approach for cancer screening and prognosis by detecting circulating tumor components like circulating tumor DNA (ctDNA) in the blood. Numerous gastric cancer-specific ctDNA biomarkers have now been identified. CtDNA analysis provides insight into genetic and epigenetic alterations in tumors, holding promise for predicting treatment response and prognosis in gastric cancer patients. This review summarizes current research on ctDNA biology and detection technologies, while highlighting clinical applications of ctDNA for gastric cancer diagnosis, prognosis, and guiding treatment decisions. Current challenges and future perspectives for ctDNA analysis are also discussed.

Objective: To reveal the molecular mechanism underlying the compatibility of Salvia miltiorrhiza Bge (S. miltiorrhiza, Dan Shen) and C. tinctorius L. (C. tinctorius, Hong Hua) as an herb pair through network pharmacology and subsequent experimental validation. Methods: Network pharmacology was applied to construct an active ingredient-efficacy target-disease protein network to reveal the unique regulation pattern of S. miltiorrhiza and C. tinctorius as herb pair. Molecular docking was used to verify the binding of the components of these herbs and their potential targets. An H9c2 glucose hypoxia model was used to evaluate the efficacy of the components and their synergistic effects, which were evaluated using the combination index. Western blot was performed to detect the protein expression of these targets. Results: Network pharmacology analysis revealed 5 pathways and 8 core targets of S. miltiorrhiza and C. tinctorius in myocardial protection. Five of the core targets were enriched in the hypoxia-inducible factor-1 (HIF-1) signaling pathway. S. miltiorrhiza-C. tinctorius achieved vascular tone mainly by regulating the target genes of the HIF-1 pathway. As an upstream gene of the HIF-1 pathway, STAT3 can be activated by the active ingredients cryptotanshinone (Ctan), salvianolic acid B (Sal. B), and myricetin (Myric). Cell experiments revealed that Myric, Sal. B, and Ctan also exhibited synergistic myocardial protective activity. Molecular docking verified the strong binding of Myric, Sal. B, and Ctan to STAT3. Western blot further showed that the active ingredients synergistically upregulated the protein expression of STAT3. Conclusion: The pharmacodynamic transmission analysis revealed that the active ingredients of S. miltiorrhiza and C. tinctorius can synergistically resist ischemia through various targets and pathways. This study provides a methodological reference for interpreting traditional Chinese medicine compatibility.

Flavonoids are pharmacologically active compounds in flowers of Chrysanthemum morifolium ‘Boju’ (C. morifolium); however, the molecular regulatory network governing flower development remains largely elusive. Flower samples were collected at four stages, namely budding (BD), bud breaking (BB), early blooming (EB), and full blooming (FB), for omics analysis. We revealed distinct transcriptional regulation patterns at these four stages of the flower from the perspective of differentially expressed unigenes (DEGs). There are 152 DEGs shared among the three comparative groups (BD vs. BB, BB vs EB, EB vs FB), wherein the expression of 44 DEGs (including AtADT6, MDL3, and ROMT) continues to be upregulated, and 85 DEGs (including CYP81E, TPS-Cin-1, and TPS-Cin-2) showed persistent downregulation with flower development. Flavonoid-targeted metabolomics identified 118 differentially abundant metabolites (DAMs) in the FB group compared to the BD stage; the top three upregulated and downregulated metabolites are Cyanidin-3-O-(6″-O-malonyl)glucoside-5-O-glucoside, Luteolin-7-O-(6″-caffeoyl)rhamnoside, Kaempferol-3-O-(6″-p-coumaroyl)glucoside and Chrysoeriol-6,8-di-C-glucoside-7-O-glucoside, Kaempferol, Kaempferol-3,7-O-dirhamnoside, respectively. These DAMs were predominantly enriched in “flavonoid biosynthesis”, “isoflavonoid biosynthesis”, and “flavone and flavonol biosynthesis” pathways. AtADT6, MDL3, ROMT, CYP81E, TPS-Cin-1, and TPS-Cin-2 were correlated with kaempferol. Our findings provide a new idea for interfering with flavonoid production, especially kaempferol, in flowers.

This research aimed to address the issue of aflatoxin B1 (AFB1) contamination, which posed severe health and economic consequences. This study involved exploring unique species resources in the Qinghai-Tibet Plateau, screening strains capable of degrading AFB1. UPLC-Q-Orbitrap HRMS and NMR were employed to examine the degradation process and identify the structure of the degradation products. Results showed that Bacillus amyloliquefaciens YUAD7, isolated from yak dung in the Qinghai-Tibet Plateau, removed 91.7% of AFB1 from TSB-AFB1 medium with an AFB1 concentration of 10 μg/mL (72 h, 37°C, pH 6.8) and over 85% of AFB1 from real food samples at 10 μg/g (72 h, 37°C), exhibiting strong AFB1 degradation activity. Bacillus amyloliquefaciens YUAD7’s extracellular secretions played a major role in AFB1 degradation mediated and could still degrade AFB1 by 43.16% after boiling for 20 min. Moreover, B. amyloliquefaciens YUAD7 demonstrated the capability to decompose AFB1 through processes such as hydrogenation, enzyme modification, and the elimination of the -CO group, resulting in the formation of smaller non-toxic molecules. Identified products include C12H14O4, C5H12N2O2, C10H14O2, C4H12N2O, with a structure consisting of dimethoxyphenyl and enoic acid, dimethyl-amino and ethyl carbamate, polyunsaturated fatty acid, and aminomethyl. The results indicated that B. amyloliquefaciens YUAD7 could be a potentially valuable strain for industrial-scale biodegradation of AFB1 and providing technical support and new perspectives for research on biodegradation products.

Background: Lipid metabolism disorders have become a major global public health issue. Due to the complexity of these diseases, additional research and drugs are needed. Oroxin A, the major component of Oroxylum indicum (L.) Kurz (Bignoniaceae), can improve the lipid profiles of diabetic and insulin-resistant (IR) rats. Because insulin resistance is strongly correlated with lipid metabolism, improving insulin resistance may also constitute an effective strategy for improving lipid metabolism. Thus, additional research on the efficacy and mechanism of oroxin An under non-IR conditions is needed. Methods: In this study, we established lipid metabolism disorder model rats by high-fat diet feeding and fatty HepG2 cell lines by treatment with oleic acid and evaluated the therapeutic effect and mechanism of oroxin A in vitro and in vivo through biochemical indicator analysis, pathological staining, immunoblotting, and immunofluorescence staining. Results: Oroxin A improved disordered lipid metabolism under non-IR conditions, improved the plasma and hepatic lipid profiles, and enhanced the lipid-lowering action of atorvastatin. Additionally, oroxin A reduced the total triglyceride (TG) levels by inhibiting sterol regulatory element-binding protein 1 (SREBP1) expression and reducing the expression of acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FASN) in vivo and in vitro. Oroxin A also reduced the total cholesterol (TC) levels by inhibiting SREBP2 expression and reducing HMGCR expression in vivo and in vitro. In addition, oroxin A bound to low-density lipoprotein receptor (LDLR) and increased AMPK phosphorylation. Conclusions: Our results suggested that oroxin A may modulate the nuclear transcriptional activity of SREBPs by binding to LDLR proteins and increasing AMPK phosphorylation. Oroxin A may thus reduce lipid synthesis and could be used for the treatment and prevention of lipid metabolism disorders.

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with a high mortality and poor survival rate. Abnormal tumor metabolism is considered a hallmark of HCC and is a potential therapeutic target. This study aimed to identify metabolism-related biomarkers to evaluate the prognosis of patients with HCC. Method The Cancer Genome Atlas (TCGA) database was used to explore differential metabolic pathways based on high and low epithelial-mesenchymal transition (EMT) groupings. Genes in differential metabolic pathways were obtained for HCC metabolism-related molecular subtype analysis. Differentially expressed genes (DEGs) from the three subtypes were subjected to Lasso Cox regression analysis to construct prognostic risk models. Stard5 expression in HCC patients was detected by western blot and immunohistochemistry (IHC), and the role of Stard5 in the metastasis of HCC was investigated by cytological experiments. Results Unsupervised clustering analysis based on metabolism-related genes revealed three subtypes in HCC with differential prognosis. A risk prognostic model was constructed based on 11 genes (STARD5, FTCD, SCN4A, ADH4, CFHR3, CYP2C9, CCL14, GADD45G, SOX11, SCIN, and SLC2A1) obtained by LASSO Cox regression analysis of the three subtypes of DEGs. We validated that the model had a good predictive power. In addition, we found that the high-risk group had a poor prognosis, higher proportion of Tregs, and responded poorly to chemotherapy. We also found that Stard5 expression was markedly decreased in HCC tissues, which was associated with poor prognosis and EMT. Knockdown of Stard5 contributed to the invasion and migration of HCC cells. Overexpression of Stard5 inhibited EMT in HCC cells. Conclusion We developed a new model based on 11 metabolism-related genes, which predicted the prognosis and response to chemotherapy or immunotherapy for HCC. Notably, we demonstrated for the first time that Stard5 acted as a tumor suppressor by inhibiting metastasis in HCC.

Abstract Background Workplace bullying experienced by clinical nurses is a critical and pervasive issue that not only detrimentally impacts nurses but also poses a significant threat to the overall quality of nursing services and patient care. This study aimed to determine the mediating role of organizational commitment in the relationship between workplace bullying and turnover intention among clinical nurses in China. Methods Participants were recruited from 40 hospitals in various provinces of China from December 2, 2021 to February 25, 2023, using convenience sampling. After obtaining hospital ethical approval and participants’ informed consent, clinical nurses (n = 585) from different nursing departments in different hospitals completed the questionnaire. The Socio-demographic Questionnaire, Negative Acts Qestionnaire, Chinese Workers’ Organizational Commitment Scale and Turnover Intention Questionnaire were used to collect general demographic data of nurses and assess workplace bullying they experienced, their level of organizational commitment and turnover intention. Descriptive statistics, Pearson correlation analyses and structural equation model were adopted to analyze the data. Results Pearson’s correlation analysis showed that that workplace bullying was significantly negatively correlated with organizational commitment (r = − 0.512, P

Agrocybe cylindracea dietary fiber (ADF) contains 95% water-insoluble dietary fiber, resulting in poor application performance. To address this issue, ADF was modified by four methods (cellulase, sodium hydroxide, high-temperature, and Lactobacillus fermentation) in this paper. By comparing the physicochemical properties, microstructures, monosaccharide compositions, and functional characteristics (antioxidant and α-glucosidase inhibitory activities in vitro) of all modified ADF samples, the optimal modification method was selected. Results showed that sodium hydroxide treatment was deemed the most effective modification method for ADF, as alkali-treated ADF (ADF-A) revealed a higher oil-holding capacity (2.02 g/g), swelling capacity (8.38 mL/g), cholesterol adsorption (6.79 mg/g), and α-glucosidase inhibitory activity (more than 70% at 0.4–0.6 mg/mL) than the other modified samples. The looser microstructure in ADF-A might be attributed to molecular rearrangement and spatial structure disruption, which resulted in smaller molecular sizes and decreased viscosity, hence improving ADF’s physicochemical and functional qualities. All these findings indicate the greater application potential of modified ADF products in food and weight-loss industries, providing a comprehensive reference for the industrial application of ADF.

Abstract The gut microbiota is a crucial modulator of Plasmodium infection in mosquitoes, including the production of anti-Plasmodium effector proteins. But how the commensal-derived effectors are translocated into Plasmodium parasites remains obscure. Here we show that a natural Plasmodium blocking symbiotic bacterium Serratia ureilytica Su_YN1 delivers the effector lipase AmLip to Plasmodium parasites via outer membrane vesicles (OMVs). After a blood meal, host serum strongly induces Su_YN1 to release OMVs and the antimalarial effector protein AmLip into the mosquito gut. AmLip is first secreted into the extracellular space via the T1SS and then preferentially loaded on the OMVs that selectively target the malaria parasite, leading to targeted killing of the parasites. Notably, these serum-induced OMVs incorporate certain serum-derived lipids, such as phosphatidylcholine, which is critical for OMV uptake by Plasmodium via the phosphatidylcholine scavenging pathway. These findings reveal that this gut symbiotic bacterium evolved to deliver secreted effector molecules in the form of extracellular vesicles to selectively attack parasites and render mosquitoes refractory to Plasmodium infection. The discovery of the role of gut commensal-derived OMVs as carriers in cross-kingdom communication between mosquito microbiota and Plasmodium parasites offers a potential innovative strategy for blocking malaria transmission.

Abstract Background The APETALA 2/ ethylene-responsive element binding factors (AP2/ERF), are thought to be associated with plant abiotic stress response, and involved in some plant hormone signaling pathways. Trichosanthes kirilowii is an important edible and medicinal crop, so far no research has been conducted on the TkAP2/ERF genes. Result In this study, a total of 135 TkERFs were identified, these genes were divided into 4 subfamilies and clustered into 13 groups. Moreover, 37 paralogous pairs were identified, with only two having Ka/Ks values greater than 1, proving that most TkERF genes underwent purifying selection during evolution. Co-expression networks constructed using transcriptome data at various flowering stages revealed that 50, 64, and 67 AP2/ERF genes correlated with members of the ethylene, gibberellin, and abscisic acid signaling pathways, respectively. When tissue cultured seedlings were treated with ETH, GA3 and ABA, 11, 12 and 17 genes were found to be up-regulated, respectively, suggesting that some members of the TkERF gene family may be involved in plant hormone signaling pathways. And under 4 ℃, PEG and NaCl treatment, 15, 20 and 19 genes were up-regulated, respectively, this suggested that these selected genes might be involved in plant abiotic stresses. Conclusions Overall, we identified 135 AP2/ERF family members, a comprehensive analysis of AP2/ERF gene expression patterns by RNA-seq and qRT-PCR showed that they played important roles in flower development and abiotic stress. This study provided a theoretical basis for the functional study of TkAP2/ERF genes and the genetic improvement of T. kirilowii.

Abstract Aiming at the problem of multi‐point power source layout planning for power systems, the output characteristics of a power system composed of wind power, photovoltaic power, hydropower, traditional thermal power, concentrated solar power and electrochemical energy storage are comprehensively analyzed. A power source multi‐point layout planning model for a power system based on complex adaptive system theory is proposed with a focus on the complementarity among these different energies and the combination of power optimization planning and complex adaptive system theory. With the minimum construction unit of various types of power sources as the ‘agent’, considering the interactions among agents and the accumulation of experiences, the behaviour rules of the model are constantly changed, the grid‐connected positions of various types of power sources are adjusted, and the optimal layout schemes for all kinds of power capacities for each node are obtained. In addition, an agent modelling method based on complex phenomena emergence with simple rules is proposed, which reveals the core idea of the complex adaptive system theory: adaptability creates complexity. Taking the new energy construction base in Northwest China as an example, the proposed method is verified to have a significant effect on improving energy consumption in the new system. Based on the current power capacity layout and the future grid structure in this area, the future power optimization scheme is determined, and it provides guiding significance for actual engineering construction.

ABSTRACT: Yak milk is rich in essential milk proteins of nutritional and therapeutic value. In this study, whey proteins of milk from 3 yak breeds (Gannan, GN; Huanhu, HH; Maiwa, MW) in China were comprehensively identified and compared using a data-independent acquisition quantitative proteomics approach. A total of 632 proteins were identified in yak milk whey samples, in which immune-related proteins were abundant. Compared with other milks, more proteins were involved in oxidation-reduction process and with ATP binding. In addition, we identified 96, 155, and 164 differentially expressed proteins (DEP) for GN versus HH, GN versus MW, and HH versus MW, respectively. “Phagosome” and “complement and coagulation cascades” were the most significant pathways for DEP of GN versus HH and GN or HH versus MW yak milk based on the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Protein-protein interaction network analysis showed that DEP for the 3 comparisons had significant biological interactions but were associated with different functions. The results provide useful information on yak milk from different breeds in China, and elucidate the biological functions of yak milk proteins.

Metabolic-associated fatty liver disease (MAFLD) is a chronic liver disease characterized by the excessive accumulation of fat in hepatocytes. However, due to the complex pathogenesis of MAFLD, there are no officially approved drugs for treatment. Therefore, there is an urgent need to find safe and effective anti-MAFLD drugs. Recently, the relationship between the gut microbiota and MAFLD has been widely recognized, and treating MAFLD by regulating the gut microbiota may be a new therapeutic strategy. Natural products, especially plant natural products, have attracted much attention in the treatment of MAFLD due to their multiple targets and pathways and few side effects. Moreover, the structure and function of the gut microbiota can be influenced by exposure to plant natural products. However, the effects of plant natural products on MAFLD through targeting of the gut microbiota and the underlying mechanisms are poorly understood. Based on the above information and to address the potential therapeutic role of plant natural products in MAFLD, we systematically summarize the effects and mechanisms of action of plant natural products in the prevention and treatment of MAFLD through targeting of the gut microbiota. This narrative review provides feasible ideas for further exploration of safer and more effective natural drugs for the prevention and treatment of MAFLD.

ObjectivesOne-carbon metabolism (OCM) significantly influences fetal growth and neurodevelopment through transferring methyl group to biomolecules, during which folate, methionine, choline and betaine function as methyl donor nutrients, while vitamin B2, B6, B12 function as enzyme cofactors, and homocysteine (Hcy) and S-adenosyl methionine (SAM) are functional metabolites. This study aimed to assess blood OCM index levels and explore their relationships among Chinese pregnant women.MethodsData were obtained from the baseline of the Mother–Child Nutrition and Health Cohort Study. Pregnant women, voluntarily recruited from September 2020 to June 2022 during antenatal examinations in five Chinese cities at 24–32 gestational weeks, provided fasting venous blood samples. Measurements included RBC and serum folate, serum vitamin B2, B6, B12, choline, betaine, methionine, total Hcy (tHcy), and plasma SAM. Sociodemographic characteristics and pregnancy-related conditions were collected via a self-designed questionnaire.ResultsOf 397 participants, 82.6% were in mid-pregnancy (24–27 gestational weeks) and 17.4% were in late-pregnancy (28–32 gestational weeks). Serum folate, vitamin B6, and B12 deficiencies were 2.5, 1.3, and 8.3%, respectively. Elevated tHcy (≥10 μmol/L) was observed in 1.8% of pregnant women. Elderly pregnant women (aged 35 and above) exhibited significantly lower serum methionine levels (p

Background and Aims: Transcriptome sequencing revealed high expression of DDR2 in oxaliplatin-resistant hepatocellular carcinoma (HCC). This study aimed to explore the role of DDR2 in oxaliplatin resistance and immune evasion in HCC. Methods: Oxaliplatin-resistant HCC cell lines were established. The interaction between DDR2 and STAT3 was investigated, along with the mechanisms involved in DDR2/STAT3-mediated PD-L1 upregulation and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) accumulation both in vitro and in vivo. Results: DDR2 was found to induce the phosphorylation of STAT3, leading to its nuclear translocation. Conversely, the activation of STAT3 enhanced DDR2 expression. A positive feedback loop involving DDR2/STAT3 was identified in oxaliplatin-resistant HCC, which was associated with PD-L1 upregulation and PMN-MDSCs accumulation. Knockdown of DDR2 and STAT3 sensitized oxaliplatin-resistant HCC cells to oxaliplatin and resulted in decreased PMN-MDSCs and increased CD8+ T cells in the tumor microenvironment. Enzyme-linked immunosorbent array and MDSC transwell migration assays indicated that oxaliplatin-resistant HCC cells recruited PMN-MDSCs through CCL20. Dual luciferase reporter assays demonstrated that STAT3 can directly enhance the transcription of PD-L1 and CCL20. Furthermore, treatment with a PD-L1 antibody in combination with CCL20 blockade had significant antitumor effects on oxaliplatin-resistant HCC. Conclusions: Our findings revealed a positive feedback mechanism involving DDR2 and STAT3 that mediates the immunosuppressive microenvironment and promotes oxaliplatin resistance and immune evasion via PD-L1 upregulation and PMN-MDSC recruitment. Targeting the DDR2/STAT3 pathway may be a promising therapeutic strategy to overcome immune escape and chemoresistance in HCC.

BackgroundThe incidence of childhood malnutrition i.e., both obesity and undernutrition, is on a rise. While there is extensive evidence of the influence of body mass index (BMI) on the survival and other important outcomes of adult cancers, the impact of childhood BMI on one of the common pediatric cancers i.e., leukemia is not well studied.MethodsSystematic search of PubMed, Scopus, and Google Scholar databases was done to identify studies that were conducted among pediatric patients with leukemia and had examined outcomes of interest based on BMI at the time of diagnosis.ResultsEffect sizes were reported as pooled hazards ratio (HR) along with 95% confidence intervals (CI). A total of 17 studies were included. Compared to pediatric leukemia patients with normal BMI, underweight (HR 1.07, 95% CI: 1.04, 1.11) and obese (HR 1.42, 95% CI: 1.18, 1.71) children with leukemia had higher risks of overall mortality. Underweight (HR 1.10, 95% CI: 1.02, 1.19) and obese (HR 1.34, 95% CI: 1.15, 1.55) pediatric leukemia patients had a tendency to lower event-free survival compared to children with normal BMI. The risk of relapse was not significant for underweight, overweight, and obese children.ConclusionsBoth underweight and obese status at the time of diagnosis were associated with poor survival outcomes in pediatric patients with leukemia.

Background Hepatocellular carcinoma (HCC) is an exceptionally immunosuppressive malignancy characterized by limited treatment options and a dismal prognosis. Macrophages constitute the primary and heterogeneous immune cell population within the HCC microenvironment. Our objective is to identify distinct subsets of macrophages implicated in the progression of HCC and their resistance to immunotherapy.Methods Intratumoral macrophage-specific marker genes were identified via single-cell RNA sequencing analyses. The clinical relevance of phospholipase A2 Group VII (PLA2G7), a pivotal enzyme in phospholipid metabolism, was assessed in patients with HCC through immunohistochemistry and immunofluorescence. Flow cytometry and an in vitro co-culture system were used to elucidate the specific role of PLA2G7 in macrophages. Orthotopic and subcutaneous HCC mouse models were employed to evaluate the potential of the PLA2G7 inhibitor in complementing immune checkpoint blockade (ICB) therapy.Results Single-cell RNA sequencing analyses disclosed predominant PLA2G7 expression in intratumoral macrophages within the HCC microenvironment. The macrophage-specific PLA2G7 was significantly correlated with poorer prognosis and immunotherapy resistance in patients with HCC. PLA2G7high macrophages represent a highly immunosuppressive subset and impede CD8 T-cell activation. Pharmacological inhibition of PLA2G7 by darapladib improved the therapeutic efficacy of anti-programmed cell death protein 1 antibodies in the HCC mouse models.Conclusions Macrophage-specific PLA2G7 serves as a novel biomarker capable of prognosticating immunotherapy responsiveness and inhibiting PLA2G7 has the potential to enhance the efficacy of ICB therapy for HCC.

Summary: Background: Abnormal liver function was frequently observed in nonalcoholic fatty liver disease (NAFLD) patients infected with SARS-CoV-2. Our aim was to explore the effect of SARS-CoV-2 inactivated vaccines on liver function abnormality among NAFLD patients with COVID-19. Methods: The multi-center retrospective cohort included 517 NAFLD patients with COVID-19 from 1 April to 30 June 2022. Participants who received 2 doses of the vaccine (n = 274) were propensity score matched (PSM) with 243 unvaccinated controls. The primary outcome was liver function abnormality and the secondary outcome was viral shedding duration. Logistic and Cox regression models were used to calculate the odds ratio (OR) and hazard ratio (HR) for the outcomes. Sensitivity analysis was conducted to assess robustness. Findings: PSM identified 171 pairs of vaccinated and unvaccinated patients. Liver function abnormality was less frequent in the vaccinated group (adjusted OR, 0.556 [95% CI (confidence interval), 0.356–0.869], p = 0.010). Additionally, the vaccinated group demonstrated a lower incidence of abnormal bilirubin levels (total bilirubin: adjusted OR, 0.223 [95% CI, 0.072–0.690], p = 0.009; direct bilirubin: adjusted OR, 0.175 [95% CI, 0.080–0.384], p

BackgroundTotal knee arthroplasty (TKA) is currently the main treatment for end-stage knee disease. The number of cases of TKA in China increased from 53,880 in 2011 to 374,833 in 2019, representing a 5.9-fold increase. Moderate to severe pain often occurs after TKA, which seriously affects postoperative rehabilitation, patient satisfaction, and overall outcome. Multimodal analgesia is considered the ideal solution. Adequate postoperative analgesia can not only reduce pain, opioid consumption, and, consequently, opioid-related adverse events, but can also reduce the length of hospital stay and costs and improve rehabilitation and patient satisfaction. ObjectiveEffective multimodal pain management in the early postoperative period is essential for anesthesiologists. Additional studies have demonstrated that a low-dose intravenous infusion of ketamine can be administered as an adjuvant drug to alleviate acute postoperative pain. Therefore, we aim to appraise the efficacy and safety of intraoperative intravenous injection of S(+)-ketamine to relieve acute pain after TKA in older patients. MethodsThis is a protocol for a randomized, placebo-controlled trial. A total of 144 participants aged 65 years and older undergoing TKA will be randomly allocated into the S(+)-ketamine and placebo groups in a 1:1 ratio. S(+)-ketamine or the placebo will be intravenously administered at 0.3 mg/kg/h during the operation by anesthesiologists. Blinded evaluation by trained investigators will be completed at 2 hours, 24 hours, and 48 hours after surgery. The primary outcome measure will be the numeric rating scale score at rest and movement at 24 hours after surgery. The secondary outcomes will include the numeric rating scale scores at rest and movement at 2 hours and 48 hours after surgery, the number of patients who require additional analgesics during the first 48 hours after operation, the total consumption of opioids or nonsteroid anti-inflammatory drugs during the first 48 hours after operation, and adverse events at 2, 24, and 48 hours after operation. ResultsThe protocol was registered at Clinical Trials.gov on February 26, 2022. It was performed in accordance with the approved guidelines and regulations of the participating institutions. Recruitment began in April 2022. Data collection is expected to conclude in September 2024. Study completion is expected in December 2024. ConclusionsA randomized, controlled, clinical study was designed to observe the analgesic effect of intraoperative intravenous administration of a lower dose of S(+)-ketamine (0.3 mg/kg/h) in older patients after TKA surgery. The protocol will appraise the efficacy and safety of intraoperative intravenous injection of S(+)-ketamine to relieve acute pain after TKA in older patients who may benefit from the administration of S(+)-ketamine. Trial RegistrationClinicalTrials.gov NCT05289050; https://clinicaltrials.gov/ct2/show/NCT05289050 International Registered Report Identifier (IRRID)DERR1-10.2196/53063

Abstract Formalin-fixed paraffin-embedded (FFPE) tissues constitute a vast and valuable patient material bank for clinical history and follow-up data. It is still challenging to achieve single cell/nucleus RNA (sc/snRNA) profile in FFPE tissues. Here, we develop a droplet-based snRNA sequencing technology (snRandom-seq) for FFPE tissues by capturing full-length total RNAs with random primers. snRandom-seq shows a minor doublet rate (0.3%), a much higher RNA coverage, and detects more non-coding RNAs and nascent RNAs, compared with state-of-art high-throughput scRNA-seq technologies. snRandom-seq detects a median of >3000 genes per nucleus and identifies 25 typical cell types. Moreover, we apply snRandom-seq on a clinical FFPE human liver cancer specimen and reveal an interesting subpopulation of nuclei with high proliferative activity. Our method provides a powerful snRNA-seq platform for clinical FFPE specimens and promises enormous applications in biomedical research.

Abstract Background Abnormal miRNA and mRNA expression and dysregulated immune microenvironment have been found to frequently induce the progression of hepatocellular carcinoma (HCC) in recent reports. In particular, the immune-related competing endogenous RNAs (ceRNA) mechanism plays a crucial role in HCC progression. However, the underlying mechanisms remain unclear. Methods Differentially expressed immune-related genes were obtained from the Immport, GEO, and TCGA databases. The mRNA and protein expression levels in HCC tissues and adjacent normal tissues were confirmed, and we further investigated the methylation levels of these biomarkers to explore their function. Then, the TIMER and TISCH databases were used to assess the relationship between immune infiltration and hub genes. Survival analysis and univariate and multivariate Cox models were used to evaluate the association between hub genes and HCC diagnosis. Hub gene expression was experimentally validated in six HCC cell lines and 15 HCC samples using qRT-PCR and immunohistochemistry. The hub genes were uploaded to DSigDB for drug prediction enrichment analysis. Results We identified that patients with abnormal miRNAs (hsa-miR-125b-5p and hsa-miR-21-5p) and their targeted genes (NTF3, PSMD14, CD320, and SORT1) had a worse prognosis. Methylation analysis of miRNA-targeted genes suggested that alteration of methylation levels is also a factor in the induction of tumorigenesis. We also found that the development of HCC progression caused by miRNA-mRNA interactions may be closely correlated with the infiltration of immunocytes. Moreover, the GSEA, GO, and KEGG analysis suggested that several common immune-related biological processes and pathways were related to miRNA-targeted genes. The results of qRT-PCR, immunohistochemistry, and western blotting were consistent with our bioinformatics results, suggesting that abnormal miRNAs and their targeted genes may affect HCC progression. Conclusions Briefly, our study systematically describes the mechanisms of miRNA-mRNA interactions in HCC and predicts promising biomarkers that are associated with immune filtration for HCC progression.

Abstract Underwater images intuitively reflect the underwater environment information. However, underwater images have defects such as colour distortion and low contrast, which seriously affect the processing of complex underwater visual tasks. Here, a novel mixed model called mixed underwater image generative adversarial network (MUGAN) is presented, consisting of a generator and corresponding discriminator. The generator is built following the U‐shaped architecture, where a mixed block of convolution and self‐attention is developed. It effectively exploits the complementarity between the two paradigms. In addition, a dual discriminator is employed to induce the generator to produce realistic images at both the global semantic and local detail levels, which is only discriminates based on the patch‐level information. Meanwhile, a multi‐term loss function is formulated to supervise adversarial training by evaluating the perceptual quality of an image based on its global content, local texture and illumination smoothness. To validate the proposed approach, extensive experiments are conducted on the public underwater datasets. MUGAN achieves promising performance in terms of colour, contrast and naturalness, showing a significant improvement over other competitive models in visual quality and quantitative metrics.

It is well known that the hippocampus is a vital brain region playing a key role in both episodic and spatial memory. Insulin receptors (InsRs) are densely distributed in the hippocampus and are important for its function. However, the effects of InsRs on the function of the specific hippocampal cell types remain elusive. In this study, hippocampal InsRs knockout mice had impaired episodic and spatial memory. GABAergic neurons and glutamatergic neurons in the hippocampus are involved in the balance between excitatory and inhibitory (E/I) states and participate in the processes of episodic and spatial memory. InsRs are located mainly at excitatory neurons in the hippocampus, whereas 8.5% of InsRs are glutamic acid decarboxylase 2 (GAD2)::Ai9-positive (GABAergic) neurons. Next, we constructed a transgenic mouse system in which InsR expression was deleted from GABAergic (glutamate decarboxylase 2::InsR fl/fl , GAD2 Cre ::InsR fl/fl ) or glutamatergic neurons (vesicular glutamate transporter 2::InsR fl/fl ,Vglut2 Cre ::InsR fl/fl ). Our results showed that in comparison to the InsR fl/fl mice, both episodic and spatial memory were lower in GAD2 Cre ::InsR fl/fl and Vglut2 Cre ::InsR fl/fl . In addition, both GAD2 Cre ::InsR fl/fl and Vglut2 Cre ::InsR fl/fl were associated with more anxiety and lower glucose tolerance. These findings reveal that hippocampal InsRs might be crucial for episodic and spatial memory through E/I balance hippocampal regulation.

Introduction: Metabolic-associated fatty liver disease (MAFLD) is a common chronic metabolic disease that seriously threatens human health. The pharmacological activity of unsaturated fatty acid-rich vegetable oil interventions in the treatment of MAFLD has been demonstrated. This study evaluated the pharmacological activity of Polygala tenuifolia Willd, which contains high levels of 2-acetyl-1,3-diacyl-sn-glycerols (sn-2-acTAGs).Methods: In this study, a mouse model was established by feeding a high-fat diet (HFD, 31% lard oil diet), and the treatment group was fed a P. tenuifolia seed oil (PWSO) treatment diet (17% lard oil and 14% PWSO diet). The pharmacological activity and mechanism of PWSO were investigated by total cho-lesterol (TC) measurement, triglyceride (TG) measurement and histopathological observation, and the sterol regulatory element-binding protein-1 (SREBP1), SREBP2 and NF-κB signaling pathways were evaluated by immunofluorescence and Western blot analyses.Results: PWSO attenuated the increases in plasma TC and TG levels. Furthermore, PWSO reduced the hepatic levels of TC and TG, ameliorating hepatic lipid accumulation. PWSO treatment effectively improves the level of hepatitic inflammation, such as reducing IL-6 levels and TNF-α level.Discussion: PWSO treatment inactivated SREBP1 and SREBP2, which are involved in lipogenesis, to attenuate hepatic lipid accumulation and mitigate the inflammatory response induced via the NF-κB signaling pathway. This study demonstrated that PWSO can be used as a relatively potent dietary supplement to inhibit the occurrence and development of MAFLD.

Abstract Primary liver cancer (PLC) is a common gastrointestinal malignancy worldwide. While hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are two major pathologic types of PLC, combined HCC and ICC (cHCC-ICC) is a relatively rare subtype that shares both hepatocyte and cholangiocyte differentiation. However, the molecular feature of this unique tumor remains elusive because of its low incidence and lack of a suitable animal model. Herein, we generated a novel spontaneous cHCC-ICC model using a Sleeping Beauty-dependent transposon plasmid co-expressing oncogenic Myc and AKT1 and a CRISPR-Cas9 plasmid expressing single-guide RNA targeting p53 into mouse hepatocytes via in situ electroporation. The histological and transcriptional analysis confirmed that this model exhibits cHCC-ICC features and activates pathways committing cHCC-ICC formation, such as TGF-β, WNT, and NF-κB. Using this model, we further screened and identified LAMB1, a protein involved in cell adhesion and migration, as a potential therapeutic target for cHCC-ICC. In conclusion, our work presents a novel genetic cHCC-ICC model and provides new insights into cHCC-ICC.

Abstract Background Though circular RNAs (circRNAs) are the key regulators in tumor carcinogenesis, they remain largely unexplored in hepatocellular carcinoma (HCC). Methods The expression of RanGAP1-derived circRNAs (circ_0063531, circ_0063534, circ_0063513, circ_0063518, circ_0063507, circ_0063723) were evaluated in eight paired HCC and normal tissues, and the correlation between circRanGAP1 (circ_0063531) expression and clinicopathological characteristics in 40 HCC patients was determined. The association between miR-27b-3p and circRanGAP1 or NRAS was predicted using bioinformatics analysis. The expression of circRanGAP1, miR-27b-3p, and NRAS were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The potential oncogenic role of circ-RanGAP1 was assessed using CCK-8, colony formation, transwell assays in vitro, subcutaneous tumor mouse model, vein tail metastatic model, and orthotopically implanted intrahepatic HCC model in vivo. Luciferase reporter and RNA immunoprecipitation (RIP) assays were used to explore the binding site between miR-27b-3p and circ-RanGAP1 or NRAS. Protein expression was detected using western blotting. The localization of miR-27b-3p and circ-RanGAP1 was investigated using fluorescence in situ hybridization (FISH). The level of immune infiltration was assessed by bioinformatics analysis, flow cytometry, and orthotopically implanted intrahepatic HCC models. Results Here, we found elevated circRanGAP1 in the cells and clinical tissues of patients with HCC. Increased circRanGAP1 levels are associated with enlarged tumors and the advanced stage of TNM. CircRanGAP1 promotes the growth, migration, and HCC cell invasion, concurrently with the growth and metastasis of tumors in-vivo. Moreover, circRanGAP1 is mainly located inside the cytoplasm. Mechanistically, circRanGAP1 as an oncogene promotes HCC progression by miR-27b-3p/NRAS/ERK axis, furthermore, affects the infiltration level of tumor-associated macrophages probably by sponging miR-27b-3p. Immune infiltration analysis shows that NRAS is positively correlated with the levels of CD68+ tumor-associated macrophages in HCC samples and that NRAS and CD68 are related to the poor outcome of HCC. Conclusion These results reveal that circRanGAP1 is a HCC oncogene that function by the miR-27b-3p/NRAS/ERK axis and regulates the infiltration levels of tumor-associated macrophages by sponging miR-27b-3p. Therefore, circRANGAP1/ NRAS axis may be an important potential treatment target against HCC.

In this study, we investigate the synergistic effect of gemcitabine (Gem) and a novel DNA vaccine in the treatment of pancreatic cancer in mice and explore the anti-tumor mechanism of this combination therapy. Fibroblast activation protein α-expressing cancer-associated fibroblasts (FAPα+ CAFs), a dominant component of the tumor microenvironment (TME), have been shown to modulate the extracellular matrix (ECM) to promote the growth, invasion, and metastasis of pancreatic cancer (PC). Therefore, FAPα+ CAFs may be an ideal target for the treatment of PC. However, treatments that solely target FAPα+ CAFs do not directly affect tumor cells. We recently constructed a novel chimeric DNA vaccine (OsFS) against human FAPα and survivin, which simultaneously targets FAPα+ CAFs and tumor cells. In Panc02 tumor-bearing mice, OsFS vaccination not only reduced the proportion of immunosuppressive cells but also promoted the recruitment of tumor-infiltrating lymphocytes, which remodeled the TME to support anti-tumor immune responses. Furthermore, after depletion of regulatory T cells (Tregs) by metronomic low-dose Gem therapy, the anti-tumor effects of OsFS were enhanced. Taken together, our results indicate that the combination of the FAPα/survivin co-targeting DNA vaccine and low-dose Gem may be an effective therapy for PC.

ABSTRACT Anopheles mosquitoes are the primary vectors for the transmission of malaria parasites, which poses a devastating burden on global public health and welfare. The recent invasion of Anopheles stephensi in Africa has made malaria eradication more challenging due to its outdoor biting behavior and widespread resistance to insecticides. To address this issue, we developed a new approach for mosquito larvae control using gut microbiota-mediated RNA interference (RNAi). We engineered a mosquito symbiotic gut bacterium, Serratia fonticola, by deleting its RNase III gene to produce double-stranded RNAs (dsRNAs) in the mosquito larval gut. We found that the engineered S. fonticola strains can stably colonize mosquito larval guts and produce dsRNAs dsMet or dsEcR to activate RNAi and effectively suppress the expression of methoprene-tolerant gene Met and ecdysone receptor gene EcR, which encode receptors for juvenile hormone and ecdysone pathways in mosquitoes, respectively. Importantly, the engineered S. fonticola strains markedly inhibit the development of A. stephensi larvae and leads to a high mortality, providing an effective dsRNA delivery system for silencing genes in insects and a novel RNAi-mediated pest control strategy. Collectively, our symbiont-mediated RNAi (smRNAi) approach offers an innovative and sustainable method for controlling mosquito larvae and provides a promising strategy for combating malaria. IMPORTANCE Mosquitoes are vectors for various diseases, imposing a significant threat to public health globally. The recent invasion of A. stephensi in Africa has made malaria eradication more challenging due to its outdoor biting behavior and widespread resistance to insecticides. RNA interference (RNAi) is a promising approach that uses dsRNA to silence specific genes in pests. This study presents the use of a gut symbiotic bacterium, Serratia fonticola, as an efficient delivery system of dsRNA for RNAi-mediated pest control. The knockout of RNase III, a dsRNA-specific endonuclease gene, in S. fonticola using CRISPR-Cas9 led to efficient dsRNA production. Engineered strains of S. fonticola can colonize the mosquito larval gut and effectively suppress the expression of two critical genes, Met and EcR, which inhibit mosquito development and cause high mortality in mosquito larvae. This study highlights the potential of exploring the mosquito microbiota as a source of dsRNA for RNAi-based pest control.

As a by-product of pomegranate processing, the recycling and reuse of pomegranate pomaces (PPs) were crucial to environmentally sustainable development. Ultrasound-assisted aqueous two-phase extraction (UA-ATPE) was applied to extract the anthocyanins (ACNs) from PPs in this study, and the central composite design response surface methodology (CCD-RSM) and artificial neural network–genetic algorithm (ANN-GA) models were utilized to optimize the extraction parameters and achieve the best yield. The results indicated that the ANN-GA model built for the ACN yield had a greater degree of fit and accuracy than the RSM model. The ideal model process parameters were optimized to have a liquid–solid ratio of 49.0 mL/g, an ethanol concentration of 28 g/100 g, an ultrasonic time of 27 min, and an ultrasonic power of 330 W, with a maximum value of 86.98% for the anticipated ACN yield. The experimental maximum value was 87.82%, which was within the 95% confidence interval. A total of six ACNs from PPs were identified by utilizing UHPLC-ESI-HRMS/MS, with the maximum content of cyanidin-3-O-glucoside being 57.01 ± 1.36 mg/g DW. Therefore, this study has positive significance for exploring the potential value of more by-products and obtaining good ecological and economic benefits in the future.

Head smut is a soil-borne fungal disease caused by Sporisorium reilianum that infects maize tassels and ears. This disease poses a tremendous threat to global maize production. A previous study found markedly different and stably heritable tassel symptoms in some maize inbred lines with Sipingtou blood after infection with S. reilianum. In the present study, 55 maize inbred lines with Sipingtou blood were inoculated with S. reilianum and classified into three tassel symptom types (A, B, and C). Three maize inbred lines representing these classes (Huangzao4, Jing7, and Chang7-2, respectively) were used as test materials to investigate the physiological mechanisms of tassel formation in infected plants. Changes in enzyme activity, hormone content, and protein expression were analyzed in all three lines after infection and in control plants. The activities of peroxidase (POD), superoxide dismutase (SOD), and phenylalanine-ammonia-lyase (PAL) were increased in the three typical inbred lines after inoculation. POD and SOD activities showed similar trends between lines, with the increase percentage peaking at the V12 stage (POD: 57.06%, 63.19%, and 70.28% increases in Huangzao4, Jing7, and Chang7-2, respectively; SOD: 27.01%, 29.62%, and 47.07% in Huangzao4, Jing7, and Chang7-2, respectively. These were all higher than in the disease-resistant inbred line Mo17 at the same growth stage); this stage was found to be key in tassel symptom formation. Levels of gibberellic acid (GA3), indole-3-acetic acid (IAA), and abscisic acid (ABA) were also altered in the three typical maize inbred lines after inoculation, with changes in GA3 and IAA contents tightly correlated with tassel symptoms after S. reilianum infection. The differentially expressed proteins A5H8G4, P09233, and Q8VXG7 were associated with changes in enzyme activity, whereas P49353, P13689, and P10979 were associated with changes in hormone contents. Fungal infection caused reactive oxygen species (ROS) and nitric oxide (NO) bursts in the three typical inbred lines. This ROS accumulation caused biofilm disruption and altered host signaling pathways, whereas NO signaling triggered strong secondary metabolic responses in the host and altered the activities of defense-related enzymes. These factors together resulted in the formation of varying tassel symptoms. Thus, interactions between S. reilianum and susceptible maize materials were influenced by a variety of signals, enzymes, hormones, and metabolic cycles, encompassing a very complex regulatory network. This study preliminarily identified the physiological mechanisms leading to differences in tassel symptoms, deepening our understanding of S. reilianum-maize interactions.

Arecoline is a pyridine alkaloid derived from areca nut in the Arecaceae family. It has extensive medicinal activity, such as analgesic, anti-inflammatory, and anti-allergic. However, the toxicity of Arecoline limits its application. Most current studies on its toxicity mainly focus on immunotoxicity, carcinogenesis, and cancer promotion. However, there are few systematic studies on its hepatotoxicity and mechanisms. Therefore, this research explored the mechanism of hepatotoxicity induced by Arecoline in rats and analyzed endogenous metabolite changes in rat plasma by combining network toxicology with metabolomics. The differential metabolites after Arecoline exposure, such as D-Lysine, N4-Acetylaminobutanal, and L-Arginine, were obtained by metabolomics study, and these differential metabolites were involved in the regulation of lipid metabolism, amino acid metabolism, and vitamin metabolism. Based on the strategy of network toxicology, Arecoline can affect the HIF-1 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, and other concerning pathways by regulating critical targets, such as ALB, CASP3, EGFR, and MMP9. Integration of metabolomics and network toxicology results were further analyzed, and it was concluded that Arecoline may induce hepatotoxicity by mediating oxidative stress, inflammatory response, energy and lipid metabolism, and cell apoptosis.

Abstract Background Hepatocellular carcinoma (HCC) is one of the most malignant tumors to threaten human life, and the survival rate remains low due to delayed diagnosis. Meanwhile, lncRNAs have great potential for application in tumor prognosis, therefore relevant research in hepatocellular carcinoma is indispensable. Methods Based on the EZH2 expression, the differentially expressed lncRNAs DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) were identified in hepatocellular carcinoma by using the TCGA database. Bioinformatics technology was utilized to determine the effect of key genes in HCC progression. The methylation and immune infiltration analyses were performed to explore the underlying function of hub genes. Finally, cellular function experiments were performed to investigate the association between identified genes and biological phenotypes in HCC. Results lncRNA-AC079061.1, hsa-miR-765, and VIPR1 were identified as independent factors that affect the prognosis of hepatocellular carcinoma. The immune infiltration analyses revealed that lncRNA-AC079061.1 can alter the immune microenvironment and thus inhibit the development of HCC by regulating the expression of an immune-related gene (VIPR1). Methylation analyses demonstrated that VIPR1 expression is negatively related to the methylation level in HCC. Experimental results suggested that lncRNA-AC079061.1 and VIPR1 were frequently downregulated in HCC cells, while hsa-miR-765 was significantly upregulated. Moreover, the lncRNA-AC079061.1/VIPR1 axis suppressed the proliferation and invasion of HCC cells. Conclusion The present study identified the lncRNA-AC079061.1/VIPR1 axis as a novel biomarker that inhibited the proliferation and invasion of hepatocellular carcinoma, affecting the ultimate disease outcome.

BackgroundPolydrug abuse is common among opioid users. Individuals who use both heroin and methamphetamine (MA) have been shown to experience a wide range of cognitive deficits. Previous research shows that repetitive transcranial magnetic stimulation (rTMS) can change cerebral cortical excitability and regulate neurotransmitter concentration, which could improve cognitive function in drug addiction. However, the stimulation time, location, and possible mechanisms of rTMS are uncertain.Methods56 patients with polydrug use disorder were randomized to receive 20 sessions of 10 Hz rTMS (n = 19), iTBS (n = 19), or sham iTBS (n = 18) to the left DLPFC. All patients used MA and heroin concurrently. Cognitive function was assessed and several related proteins including EPI, GABA-Aα5, IL-10, etc. were quantified by ELISA before and after the treatment.ResultsBaseline RBANS scores were lower than normal for age (77.25; IQR 71.5–85.5). After 20 treatment sessions, in the iTBS group, the RBANS score increased by 11.95 (95% CI 0.02–13.90, p = 0.05). In particular, there were improvements in memory and attention as well as social cognition. Following treatment, serum EPI and GABA-Aα5 were reduced and IL-10 was elevated. The improvement of immediate memory was negatively correlated with GABA-Aα5 (r = −0.646, p = 0.017), and attention was positively correlated with IL-10 (r = 0.610, p = 0.027). In the 10 Hz rTMS group, the improvement of the RBANS total score (80.21 ± 14.08 before vs.84.32 ± 13.80 after) and immediate memory (74.53 ± 16.65 before vs.77.53 ± 17.78 after) was statistically significant compared with the baseline (p 0.05).ConclusionIntermittent theta burst stimulation to the left DLPFC may improve cognitive function in polydrug use disorder patients. Its efficacy appears to be better than that of 10 Hz rTMS. The improvement of cognitive function may be related to GABA-Aα5 and IL-10. Our findings preliminarily demonstrate the clinical value of iTBS to the DLPFC to augment neurocognitive recovery in polydrug use disorders.

Obesity is strongly associated with the occurrence and development of many types of cancers. Patients with obesity and cancer present with features of a disordered gut microbiota and metabolism, which may inhibit the physiological immune response to tumors and possibly damage immune cells in the tumor microenvironment. In recent years, bariatric surgery has become increasingly common and is recognized as an effective strategy for long-term weight loss; furthermore, bariatric surgery can induce favorable changes in the gut microbiota. Some studies have found that microbial metabolites, such as short-chain fatty acids (SCFAs), inosine bile acids and spermidine, play an important role in anticancer immunity. In this review, we describe the changes in microbial metabolites initiated by bariatric surgery and discuss the effects of these metabolites on anticancer immunity. This review attempts to clarify the relationship between alterations in microbial metabolites due to bariatric surgery and the effectiveness of cancer treatment. Furthermore, this review seeks to provide strategies for the development of microbial metabolites mimicking the benefits of bariatric surgery with the aim of improving therapeutic outcomes in cancer patients who have not received bariatric surgery.

Pre-mRNA processing factor 19 (PRP19) is elevated in hepatocellular carcinoma (HCC); however, little is known about its function in DNA damage repair in HCC. In this study, analysis of The Cancer Genome Atlas data and our tumor models after ionizing radiation (IR) treatment indicated that increased expression of PRP19 was positively correlated with DNA damage repair. Gain of PRP19 expression induced by plasmids resulted in decreases in apoptosis and double-strand breaks (DSBs), and an increase in cell survival after IR. Loss of PRP19 expression induced by small interfering RNAs resulted in the accumulation of apoptosis and DSBs, and a decrease in cell survival. Mechanistically, the effect of PRP19 on DNA damage repair was mediated by the modulation of cyclin D1 expression in HCC. PRP19 controlled the translation of cyclin D1 by modulating eukaryotic initiation factor 4E. PRP19 affected the DNA damage repair ability of cyclin D1 by interacting with the WD40 domain. The combination of PRP19 and cyclin D1 was more valuable than each single marker for predicting the prognosis of patients. Taken together, the present results demonstrate that PRP19 promotes DNA damage repair by modulating cyclin D1 expression and function, thereby contributing to the radioresistance in HCC.

Currently, modular building is undergoing vigorous development in China, and has provided a significant advantage in many fields, but its quality is difficult to guarantee. The key is to improve the design process, shorten the development cycle, and enhance competitiveness. Therefore, it is necessary to establish and optimize the design process of modular buildings. This article was based on the DSM and adopted a parallel design to model the modular building design process. Based on this, the design process was analyzed and optimized to shorten the development cycle and reduce costs. At the same time, considering the differences in attributes between different stages of the modular building design process, a DSM model with different resolutions was constructed based on the content and interrelationships of modular building design. The schedule and cost of the design process were evaluated through simulation, the differences between different resolution models were compared, and a more reliable estimate of the schedule and cost of the design process was obtained. Considering the workload and difficulty of high-resolution modeling, an approximate estimation method based on low-resolution modeling was proposed to alleviate the dependence on high-resolution models and modeling costs to some extent, thereby effectively improving the predictability of the design process and providing necessary reference for product design management personnel.

Abstract Background Interferon regulatory factor 2 (IRF-2) acts as an anti-oncogene in gastric cancer (GC); however, the underlying mechanism remains unknown. Methods This study determined the expression of IRF-2 in GC tissues and adjacent non-tumor tissues using immunohistochemistry (IHC) and explored the predictive value of IRF-2 for the prognoses of GC patients. Cell function and xenograft tumor growth experiments in nude mice were performed to test tumor proliferation ability, both in vitro and in vivo. Chromatin immunoprecipitation sequencing (ChIP-Seq) assay was used to verify the direct target of IRF-2. Results We found that IRF-2 expression was downregulated in GC tissues and was negatively correlated with the prognoses of GC patients. IRF-2 negatively affected GC cell proliferation both in vitro and in vivo. ChIP-Seq assay showed that IRF-2 could directly activate AMER-1 transcription and regulate the Wnt/β-catenin signaling pathway, which was validated using IHC, in both tissue microarray and xenografted tumor tissues, western blot analysis, and cell function experiments. Conclusions Increased expression of IRF-2 can inhibit tumor growth and affect the prognoses of patients by directly regulating AMER-1 transcription in GC and inhibiting the Wnt/β-catenin signaling pathway.

The high penetration of variable renewable energies requires the flexibility from both the generation and demand sides. This raises the necessity of modeling stochastic and flexible energy resources in power system operation. However, some distributed energy resources have both stochasticity and flexibility, e.g., prosumers with distributed photovoltaics and energy storage, and plug-in electric vehicles with stochastic charging behavior and demand response capability. Such partly controllable participants pose challenges to modeling the aggregate behavior of large numbers of entities in power system operation. This paper proposes a new perspective on the aggregate modeling of such energy resources in power system operation. Specifically, a unified controllability-uncontrollability-decomposed model for various energy resources is established by modeling the controllable and uncontrollable parts of energy resources separately. Such decomposition enables the straightforward aggregate modeling of massive energy resources with different controllabilities by integrating their controllable components with linking constraints and uncontrollable components with dependent discrete convolution. Furthermore, a two-stage stochastic unit commitment model based on the proposed model for power system operation is established. The proposed model is tested using a three-bus system and real Qinghai provincial power grid of China. The result shows that this model is able to characterize at high accuracy the aggregate behavior of massive energy resources with different levels of controllability so that their flexibility can be fully explored.

Abstract Background Ginseng red skin root syndrome (GRS) is one of the most common ginseng (Panax ginseng Meyer) diseases. It leads to a severe decline in P. ginseng quality and seriously affects the P. ginseng industry in China. However, as a root disease, the characteristics of the GRS rhizosphere microbiome are still unclear. Methods The amplicon bacterial 16 S rRNA genes and fungal ITS (Internal Transcribed Spacer) regions Illumina sequencing technology, combined with microbial diversity and composition analysis based on R software, was used to explore the relationship between soil ecological environment and GRS. Results There were significant differences in the diversity and richness of soil microorganisms between the rhizosphere with different degrees of disease, especially between healthy P. ginseng (HG) and heavily diseased groups. The variation characteristics of microbial abundance in different taxa levels were analyzed. The interaction network of rhizosphere microorganisms of P. ginseng under GRS background was established. We also found that different P. ginseng rhizosphere microbial communities have multiple changes in stability and complexity through the established interaction network. Microbes closely related to potential pathogenic fungi were also identified according to the interaction network, which provided clues for looking for biological control agents. Finally, the Distance-based redundancy analysis (dbRDA) results indicated that total phosphorus (TP), available potassium (AK), available phosphorus (AP), catalase (CAT), invertase (INV) are the key factors that influence the microbial communities. Moreover, the content of these key factors in the rhizosphere was negatively correlated with disease degrees. Conclusions In this study, we comprehensively analyzed the rhizosphere characteristics of P. ginseng with different levels of disease, and explored the interaction relationship among microorganisms. These results provide a basis for soil improvement and biological control of field-grown in the future.

As a consumer product, black chokeberry (Aronia melanocarpa) is difficult to consume due to its pungent taste. It is mainly used in various food industries to produce a variety of juices, preserves, extracts, fruit teas and nutritional supplements. Traditionally, Potawatomi Native Americans used black chokeberry to treat colds, coughs and fever. It has been found to contain numerous active ingredients. Currently, there are many health and medical products that contain black chokeberry. The purpose of this review is to understand the nutritional benefits of black chokeberry and to explore its beneficial effects on biological systems in vitro, thereby emphasizing its therapeutic prospects.