Search

The role of facile curcumin dispersion and its hydrophobic complexation onto GLP, in the form of shell (GLPC-E), core (GLPE-C) and with synergy (GLP-ECE), on the protein interfacial and emulsion stabilization was investigated. Turbiscan instability index, microrheological elasticity, viscosity and solid-liquid balance values showed that the O/W emulsion stability was in the order of GLP-E < GLPC-E < GLPE-C < GLP-ECE. GLP-ECE also gave the most reduced D [4, 3] (8.11 ± 0.14 μm) with lowest indexes of flocculation (2.80 ± 0.05 %) and coalescence (2.83 ± 0.10 %) at day 5. Interfacial shear rheology suggested the GLP-curcumin complexation fortified the GLP interfacial gelling and then the efficiency as steric stabilizer, especially of core-shell complexation (14.2 mN/m) that showed the most sufficient in-plane protein interaction against strain. Dilatational elasticity and desorption observation revealed the synergistic curcumin complexation facilitated GLP unfolding and macromolecular association at O/W interface, as was also verified from SEM image and surface hydrophobicity (from 36.23 to 76.04). Overall, this study firstly reported the facile curcumin bi-physic dispersion and GLP complexation in improving the emulsion stabilizing efficiency of the protein by advancing its interfacial stabilization., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

To investigate the value of serum eotaxin-2, neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) in the diagnosis and prognosis of colorectal cancer (CRC). The association between different clinicopathological characteristics and eotaxin-2, NLR, and PLR in different patient groups was evaluated. The combined detection indicator and the combined detection's predictive effect on distant metastasis were examined. The receiver operating characteristic (ROC) curve was drawn to evaluate the efficacy of combined detection. The association between eotaxin-2, inflammation markers, and postoperative complications was assessed. Multivariate analysis to investigate the factors affecting the prognosis of patients with CRC. We detected a marked positive correlation between NLR and PLR (p < 0.05, r= 0.209). The AUC of serum eotaxin-2 combined with inflammation markers was 0.889, which was higher than single diagnosis. Compared with the single eotaxin-2 test, the combined detection of eotaxin-2 and inflammation markers might improve the specificity of CRC assessment. In univariate analysis, age, surgical method, high eotaxin-2, and high NLR were associated with postoperative complications. In multivariate analysis, age (≥ 60 years), high eotaxin-2, and high NLR were independent risk elements influencing postoperative complications of CRC. The distant metastasis, TNM staging -Ⅳ stage, NLR ≥ 3.18, and PLR ≥ 193 were independent factors affecting the prognosis of patients with CRC. The combined detection of eotaxin-2 and inflammatory markers has a particular value in improving the diagnosis of CRC, predicting distant metastasis, and guiding the frequency of reexamination after radical resection of CRC.

Osteoporosis is the most common bone disorder, in which an imbalance between osteoclastic bone resorption and osteoblastic bone formation disrupts bone homeostasis. Osteoporosis management using anti-osteoclastic agents is a promising strategy; however, this remains an unmet need. Sphingosine-1-phosphate (S1P) and its receptors (S1PRs) are essential for maintaining bone homeostasis. Here, we identified that Siponimod, a Food and Drug Administration-approved S1PR antagonist for the treatment of multiple sclerosis, shows promising therapeutic effects against osteoporosis by inhibiting osteoclast formation and function. We found that Siponimod inhibited osteoclast formation in a dose-dependent manner without causing cytotoxicity. Podosome belt staining and bone resorption assays indicated that Siponimod treatment impaired osteoclast function. Western blot and qPCR assays demonstrated that Siponimod suppressed the expression of osteoclast-specific markers, including C-Fos, Nftac1, and Ctsk. Mechanistically, we validated that Siponimod downregulated receptor activator of nuclear factor kappa B ligand (RANKL)-induced Mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathways during osteoclastogenesis. Moreover, in a preclinical mouse model, Siponimod prevented ovariectomy-induced bone loss by suppressing osteoclast activity in vivo. Collectively, these results suggest that Siponimod could serve as an alternative therapeutic agent for the treatment of osteoporosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Immune-related GTPase M (IRGM) induces autophagy and suppresses inflammation, but its putative role and signaling mechanism remain undefined in the pathogenesis of liver failure. This study aimed to address how IRGM attenuates inflammatory injury by regulating autophagy in liver failure. In this study, a total of 10 patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and 10 healthy controls were prospectively enrolled. Intrahepatic expression of IRGM/Irgm1, NLRP3 inflammasome (NLRP3, ASC, and caspase-1), autophagy-related proteins (LC3II, P62), and inflammatory cytokines (IL-1β, TNF-α) were measured. Autophagy was activated by rapamycin (4 mg/kg) in an acute liver failure (ALF) mouse model, which was used to further study the expression of Irgm1, NLRP3 inflammasome, autophagy-related proteins, and inflammatory cytokines using both qRT-PCR and Western blot analyses. Irgm1 expression was knocked down using Irgm1 short hairpin RNA (shRNA) in lipopolysaccharide (LPS)-induced AML12 cells to investigate the effects of Irgm1 deletion on autophagy and inflammation. We found that the expression of IRGM and autophagy-related proteins was significantly downregulated while the NLRP3 inflammasome was significantly upregulated in the livers of HBV-ACLF patients and the ALF mouse model (all P < 0.05). Rapamycin-induced autophagy ameliorated intrahepatic NLRP3 inflammasome activation and decreased inflammation and necrosis in the ALF mice. Irgm1 knockdown decreased autophagy and significantly upregulated NLRP3 inflammasome activation in AML12 cells (all P < 0.05). Rapamycin-induced autophagy also protected against hepatocyte injury following LPS stimulation in vitro by inhibiting NLRP3 inflammasome activation. Thus, IRGM/Irgm1 alleviates inflammation-mediated hepatocyte injury by regulating autophagy. This study provides new insight into potential molecular targets to treat liver failure., (© 2024. The Author(s).)

Elucidation on the emulsifying behaviors of goose liver protein (GLP) from interfacial perspective was scarce when protein charging was altered. This work aimed to elucidate the role of phosphorylation on the interfacial associative interaction and then emulsion stabilizing properties of GLP using three structurally relevant phosphates of sodium trimetaphosphate (STMP), sodium tripolyphosphate (STPP) and sodium pyrophosphate (TSPP). A monotonic increment of protein charging treated from STMP, STPP to TSPP caused progressively increased particle de-aggregation, surface hydrophobicity and structural flexibility of GLP. Compared with STMP and TSPP, STPP phosphorylation rendered the most strengthened interfacial equilibrium pressure (11.98 ± 0.24 mN/m) due to sufficient unfolding but moderated charging character conveyed. Desorption curve and interfacial protein microstructure indicated that STPP phosphorylation caused the highest interfacial connectivity between proteins adsorbed onto the same droplet, as was also verified by interfacial elastic modulus (10.3 ± 0.21 mN/m). STPP treated GLP also yielded lowest droplet size (8.16 ± 0.10 μm), flocculation (8.18%) and Turbiscan stability index (8.78 ± 0.36) of emulsion but most improved microrheological properties. Overall, phosphorylation functioned itself in fortifying the intradroplet protein-protein interaction but restraining the interdroplet aggregation, and STPP phosphorylation endowed the protein with most enhanced interfacial stabilization and emulsifying efficiency., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Gout prediction is essential for the development of individualized prevention and treatment plans. Our objective was to develop an efficient and interpretable machine learning (ML) model using the SHapley Additive exPlanation (SHAP) to link dietary fiber and triglyceride-glucose (TyG) index to predict gout., Methods: Using datasets from the National Health and Nutrition Examination Survey (NHANES) (2005-2018) population to study dietary fiber, the TyG index was used to predict gout. After evaluating the performance of six ML models and selecting the Light Gradient Boosting Machine (LGBM) as the optimal algorithm, we interpret the LGBM model for predicting gout using SHAP and reveal the decision-making process of the model., Results: An initial survey of 70,190 participants was conducted, and after a gradual exclusion process, 12,645 cases were finally included in the study. Selection of the best performing LGBM model for prediction of gout associated with dietary fiber and TyG index (Area under the ROC curve (AUC): 0.823, 95% confidence interval (CI): 0.798-0.848, Accuracy: 95.3%, Brier score: 0.077). The feature importance of SHAP values indicated that age was the most important feature affecting the model output, followed by uric acid (UA). The SHAP values showed that lower dietary fiber values had a more pronounced effect on the positive prediction of the model, while higher values of the TyG index had a more pronounced effect on the positive prediction of the model., Conclusion: The interpretable LGBM model associated with dietary fiber and TyG index showed high accuracy, efficiency, and robustness in predicting gout. Increasing dietary fiber intake and lowering the TyG index are beneficial in reducing the potential risk of gout., (© 2024. The Author(s).)

Background: The relationship between systemic inflammatory index (SII), sex steroid hormones, dietary antioxidants (DA), and gout has not been determined. We aim to develop a reliable and interpretable machine learning (ML) model that links SII, sex steroid hormones, and DA to gout identification., Methods: The dataset we used to study the relationship between SII, sex steroid hormones, DA, and gout was from the National Health and Nutrition Examination Survey (NHANES). Six ML models were developed to identify gout by SII, sex steroid hormones, and DA. The seven performance discriminative features of each model were summarized, and the eXtreme Gradient Boosting (XGBoost) model with the best overall performance was selected to identify gout. We used the SHapley Additive exPlanation (SHAP) method to explain the XGBoost model and its decision-making process., Results: An initial survey of 20,146 participants resulted in 8,550 being included in the study. Selecting the best performing XGBoost model associated with SII, sex steroid hormones, and DA to identify gout (male: AUC: 0.795, 95% CI: 0.746- 0.843, accuracy: 98.7%; female: AUC: 0.822, 95% CI: 0.754- 0.883, accuracy: 99.2%). In the male group, The SHAP values showed that the lower feature values of lutein + zeaxanthin (LZ), vitamin C (VitC), lycopene, zinc, total testosterone (TT), vitamin E (VitE), and vitamin A (VitA), the greater the positive effect on the model output. In the female group, SHAP values showed that lower feature values of E2, zinc, lycopene, LZ, TT, and selenium had a greater positive effect on model output., Conclusion: The interpretable XGBoost model demonstrated accuracy, efficiency, and robustness in identifying associations between SII, sex steroid hormones, DA, and gout in participants. Decreased TT in males and decreased E2 in females may be associated with gout, and increased DA intake and decreased SII may reduce the potential risk of gout., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cao and Hu.)

Encouraged by the successful fabrication of C 60 -GNR (GNR=graphene nanoribbon) single-molecule transistors in experiments, four Fe-containing derived double-layered devices of Fe@C 60 -GNR are designed by employing different electrode linkages and their transport properties are investigated by using density functional theory (DFT) and nonequilibrium Green's function (NEGF) methods. Regardless of electrode connection, all these devices give rise to a smaller negative differential resistance (NDR) peak at V=0.2 and a higher peak at 1.2 V, suggesting their stable maneuverability as molecular devices and good candidates for developing on(off)-off(on)-on(off) current switches. The macroscopic NDR performance depends on the delocalization character and the crossing mechanism of the frontier orbitals. The peak-to-valley current ratios (R max ) range from 454 to 2737, determined by the electrode linkage. Such a large R max -value is necessary for developing dynamic random-access memory (DRAM) cells. Encapsulating the Fe atom inside C 60 not only improves the conductivity but also introduces the spin-polarized transport property. The spin-filtering efficiency (SFE) of almost all devices oscillates up and down in response to the bias voltage, indicating the possibility of designing on(off)-off(on)-on(off) spin switches and up-down spin switches. All these fascinating properties provide an important clue for designing similar molecular devices with multiple functions by trapping magnetic transition metal atoms inside fullerenes., (© 2024 Wiley‐VCH GmbH.)

A prior investigation revealed that a lack of Zinc (Zn) could hinder intestinal cell proliferation in broiler chickens; however, the mechanisms responsible for this effect remain unclear. We aimed to investigate the possible mechanisms of dietary Zn deficiency in inhibiting the jejunal cell proliferation of broilers. For this study, a total of 112 chickens (21 days old) were randomly divided into two treatments (seven replicate cages per treatment, eight chickens per replicate cage): the control group (CON) and the Zn deficiency group. The duration of feeding was 21 d. Chickens in the control group were provided with a basal diet containing an extra addition of 40 mg Zn/kg in the form of Zn sulfate, whereas chickens in the Zn deficiency group were given the basal diet with no Zn supplementation. The results indicated that, in comparison to the CON, Zn deficiency increased ( p < 0.05) the duodenal and jejunal crypt depth (CD) of broilers on d 28 and jejunal and ileal CD on d 35, and decreased ( p < 0.05) the duodenal, jejunal, and ileal villus height/crypt depth (VH/CD) on d 28 and the jejunal VH, jejunal and ileal villus surface area, and VH/CD on d 35. Furthermore, Zn deficiency decreased ( p < 0.0001) the number of proliferating cell nuclear antigen-positive cells and downregulated ( p < 0.01) the mRNA or protein expression levels of phosphatidylinositol 3-kinase (PI3K), phosphorylated PI3K, phosphorylated serine-threonine kinase (AKT), phosphorylated mechanistic target of rapamycin (mTOR), G protein-coupled receptor 39 (GPR39), and extracellular-regulated protein kinase, but upregulated ( p < 0.05) the mRNA or protein expression levels of P38 mitogen-activated protein kinase, c-jun N-terminal kinase (JNK) 1 and JNK2, and phosphorylated protein kinase C in the jejunum of the broilers on d 42. It was concluded that dietary Zn deficiency inhibited cell proliferation possibly via the GPR39-mediated suppression of the PI3K/AKT/mTOR signaling pathway in the jejunum of broilers.

The appropriateness of animal by-product proteins as emulsifiers is barely explored compared to their meat counterparts. This paper focused on improving interfacial and emulsifying properties of modified goose liver protein using three structurally relevant polyphenols either enhanced by pH shifting (P-catechin, P-quercetin and P-rutin) or not (catechin, quercetin and rutin). Due to its high hydrophobicity and limited steric hindrance, quercetin was more sufficient to hydrophobically interact (ΔH > 0, ΔS > 0) with MGLP than catechin and rutin. Results showed that polyphenol interactive affinity was positively correlated to surface hydrophobicity but negatively to size and aggregation extent of MGLP. Interfacial pressure and dilatational elastic modulus implied that synergistic polyphenol interaction and pH shifting favored the interfacial adsorption and macromolecular association of MGLP, particularly for P-quercetin with the values reached to 19.9 ± 2.0 mN/m and 22.9 ± 1.2 mN/m, respectively. Emulsion stabilized by P-quercetin also maintained highest physical and oxidative stabilities regarding the lowest D [4,3] (3.78 ± 0.27 μm) and creaming index (8.38 ± 0.43 %), together with highest mono- (19.51 %) and polyunsaturated fatty acid content (29.39 %) during storage. Overall, chemical structure of polyphenols may be determining in fabricating MGLP-polyphenol complexes with improved emulsion stabilization efficiency., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Babesiosis is a malaria-like disease in humans and animals that is caused by Babesia species, which are tick-transmitted apicomplexan pathogens. Babesia duncani causes severe to lethal infection in humans, but despite the risk that this parasite poses as an emerging pathogen, little is known about its biology, metabolic requirements or pathogenesis. Unlike other apicomplexan parasites that infect red blood cells, B. duncani can be continuously cultured in vitro in human erythrocytes and can infect mice resulting in fulminant babesiosis and death. We report comprehensive, detailed molecular, genomic, transcriptomic and epigenetic analyses to gain insights into the biology of B. duncani. We completed the assembly, 3D structure and annotation of its nuclear genome, and analysed its transcriptomic and epigenetics profiles during its asexual life cycle stages in human erythrocytes. We used RNA-seq data to produce an atlas of parasite metabolism during its intraerythrocytic life cycle. Characterization of the B. duncani genome, epigenome and transcriptome identified classes of candidate virulence factors, antigens for diagnosis of active infection and several attractive drug targets. Furthermore, metabolic reconstitutions from genome annotation and in vitro efficacy studies identified antifolates, pyrimethamine and WR-99210 as potent inhibitors of B. duncani to establish a pipeline of small molecules that could be developed as effective therapies for the treatment of human babesiosis., (© 2023. The Author(s).)

Mitochondrial ribosomal protein L7/L12 (MRPL12) is a member of the mitochondrial ribosomal proteins (MRPs). However, the biological function of MRPL12 in lung adenocarcinoma (LUAD) remains unclear. The expression and prognostic value of MRPL12 in LUAD were systematically analyzed using UALCAN, TIMER, HPA, Kaplan-Meier plotter, and GEPIA databases. The relationship between MRPL12 and immune infiltrates was investigated using TIMER and TISIDB databases. The clinical significance of MRPL12 in LUAD patients was validated using a tissue microarray (TMA). Cellular functional experiments were carried out to examine the influences of MRPL12 knockdown on cell proliferation, migration, and invasion. MRPL12 was significantly upregulated in LUAD samples, and high MRPL12 expression was correlated with worse prognosis. MRPL12 expression was markedly associated with immunomodulators, chemokines, and infiltration levels of multiple immune cells. Furthermore, TMA results confirm the upregulation of MRPL12 expression in LUAD, and MRPL12 was identified as an independent prognostic factor in LUAD patients. MRPL12 knockdown inhibited proliferation, migration, and invasion of LUAD cells. These data indicate that MRPL12 is a prognostic biomarker and correlated with immune infiltrates in LUAD. Therefore, MRPL12 shows potential as a therapeutic target for LUAD.

Duck liver is an important by-product of duck food. In this study, we investigated the effects of glucose, fructose, and xylose on the antioxidant properties of glycosylated products of duck liver protein and their protective effects on HepG2 cells. The results show that the glycosylation products of the three duck liver proteins (DLP-G, DLP-F, and DLP-X) all exhibit strong antioxidant activity; among three groups, DLP-X shows the strongest ability to scavenge DPPH, ·OH free radicals, and ABTS + free radicals. The glycosylated products of duck liver protein are not toxic to HepG2 cells and significantly increase the activity of antioxidant enzymes such as SOD, CAT, and GSH-Px in HepG2 cells at the concentration of 2.0 g/L, reducing oxidative stress damage of cells ( p < 0.05). DLP-X has a better effect in reducing oxidative damage and increasing cellular activity in HepG2 cells than DLP-G and DLP-F ( p < 0.05). In this study, the duck liver protein glycosylated products by glucose, fructose, and xylose were named as DLP-G, DLP-F, and DLP-X, respectively.

Key to the success of legumes is the ability to form and maintain optimal symbiotic nodules that enable them to balance the trade-off between symbiosis and plant growth. Cytokinin is essential for homeostatic regulation of nodulation, but the mechanism remains incompletely understood. Here, we show that a B-type response regulator GmRR11d mediates systemic inhibition of nodulation. GmRR11d is induced by rhizobia and low level cytokinin, and GmRR11d can suppress the transcriptional activity of GmNSP1 on GmNIN1a to inhibit soybean nodulation. GmRR11d positively regulates cytokinin response and its binding on the GmNIN1a promoter is enhanced by cytokinin. Intriguingly, rhizobial induction of GmRR11d and its function are dependent upon GmNARK that is a CLV1-like receptor kinase and inhibits nodule number in shoots. Thus, GmRR11d governs a transcriptional program associated with nodulation attenuation and cytokinin response activation essential for systemic regulation of nodulation., (© 2022. The Author(s).)

Background: Increased interferon (IFN)-gamma inducible protein-10 (IP-10) level has been shown to be associated with sustained virologic responses (SVRs) to pegylated interferon-alpha 2a/ribavirin-based therapy in patients with chronic hepatitis C (CHC). We investigated the relationship between IP-10 and treatment response in patients with CHC treated with direct-acting antiviral agents (DAAs) therapy., Methods: We measured the dynamic changes of IP-10 in samples from 90 patients with CHC. The serum IP-10 levels, intrahepatic expressions of IP-10 mRNA, and protein were determined, respectively. For the in vitro experiments, the expression changes of IP-10 in hepatitis C virus (HCV)-replicating Huh-7 cells with or without non-structural protein 5A (NS5A) inhibitor were analyzed using real-time reverse transcription-polymerase chain reaction and Western blotting., Results: Patients with chronic hepatitis C had increased baseline IP-10 levels, intrahepatic IP-10 mRNA, and protein expression. After initiating DAAs therapy, serum IP-10 levels decreased gradually in patients who achieved cure, whereas in patients who failed the therapy, IP-10 levels did not change significantly or recovered from the initial decline. Multivariate logistic regression analysis confirmed that baseline IP-10 level ≤ 450 pg/ml and decline >30% at 12 weeks independently predicted the SVR in patients with CHC who received DAAs. In vitro , the expression of IP-10 mRNA and protein in HCV-replicating Huh-7 cells increased significantly. However, such activities were downregulated by NS5A inhibitor, followed by the reduction of HCV RNA levels and a decline in IP-10 levels., Conclusion: IP-10 interfered with HCV replication in hepatocytes and the dynamic decline in IP-10 levels during DAA treatment predicted the SVR in patients with CHC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Hu, Zhang, Luo, Ma, Lu, Liang, Xu, Zhao and Pan.)

This paper provides an annual review of capillary electrophoresis (CE) technology in 2021. A total of 291 research papers related to CE technology published in 2021 were retrieved from the ISI Web of Science using the keywords, "capillary electrophoresis-mass spectrometry" "capillary isoelectric focusing" "micellar electrokinetic chromatography", or "capillary electrophoresis" (not "capillary electrochromatography" "microchip" and "capillary monolithic column"). In addition, nine research papers related to CE technology in Chinese journals were reviewed: Chinese Journal of Chromatography and Chinese Journal of Analytical Chemistry . This review focused on seven papers published in Coordination Chemistry Reviews , Angewandte Chemie-International Edition , Nature Protocols , TrAC-Trends in Analytical Chemistry , and Signal Transduction and Targeted Therapy with impact factors (IFs) greater than 10.0, as well as 42 papers reported in Analytical Chemistry , Analytica Chimica Acta , Talanta , and Food Chemistry with IFs between 5.0 and 10.0. This review also provides a comprehensive overview of representative CE works in Journal of Chromatography A and Electrophoresis with IFs<5.0, as well as important Chinese journals, Chinese Journal of Chromatography and Chinese Journal of Analytical Chemistry . According to the IF, this paper introduces the representative work of CE-related papers to allow readers to quickly understand the important research progress of CE technology in the past year.

Background: MicroRNAs (miRNAs) acting as tumour suppressors or oncogenes, known as oncomiRs, are a promising new focus in targeted therapies for cancer. Approximately 16% of breast cancer patients have pre-existing diabetes. Breast cancer with type 2 diabetes mellitus (BDM) is provided with its unique biological characteristics and clinical characteristics. This study primarily investigated the therapeutic potential and regulatory mechanism of miR-29a in patients with BDM., Methods: The significance of miR-29a in BDM was analyzed by real-time reverse transcriptase polymerase chain reaction (qRT-PCR) in breast tissues. A cell model for BDM was established by using MDA-MB-231 cells cultured in 3T3-L1 adipocytes cultured with high levels of glucose and insulin. A type 2 diabetes mellitus (T2DM) mouse model was induced in female BALB/c mice through a high-fat diet plus low doses of streptozotocin (STZ). The xenograft mouse-model for BDM was established on these T2DM mouse by using MDA-MB-231 cells. Then the biological effects of miR-29a knockdown mediated by lentivirus-shRNAs on cell proliferation, apoptosis, cell cycle, and migration were investigated., Results: Our results indicated that miR-29a was upregulated in patients with BDM, which correlated with a worse prognosis. In human breast cancer cells, miR-29a knockdown reduced cell proliferation and cell migration and invasion in BDM. In the T2DM xenograft, miR-29a knockdown suppressed MDA-MB-231 cells tumorigenesis and metastasis. We also demonstrated that miR-29a promoted BDM cell growth and metastasis by targeting Sirtuin 1 (SIRT1)., Conclusions: Our findings indicated that anti-miR-29a inhibited cell proliferation and invasion in BDM by targeting SIRT1. We believe anti-miR-29a may represent a novel therapeutic approach for the management of patients with BDM., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-824/coif). The authors have no conflicts of interest to declare., (2022 Translational Cancer Research. All rights reserved.)

Background: It remains controversial whether there is a difference in the prognosis of intracytoplasmic sperm injection (ICSI) using frozen or fresh testicular sperm in patients with obstructive azoospermia (OA). Moreover, in the available studies, few have tracked neonatal outcomes. This study aimed to compare the pregnancy and neonatal outcomes of ICSI using cryopreserved sperm versus fresh sperm collected by testicular sperm aspiration (TESA)., Methods: A total of 317 OA patients treated with ICSI in a university affiliated hospital from January 2016 to December 2020 were included in this study. The participants were divided into two groups according to the type of sperm used for ICSI: frozen sperm group (n=154) and fresh sperm group (n=163). The pregnancy and neonatal outcomes of the two groups were compared., Results: The data produced by this study showed no significant statistical difference in the 2 pronuclei (2PN) fertilization rate, 2PN cleavage rate, high-quality blastocyst rate, and the average number of transferred embryos in the frozen and fresh sperm groups. Similarly, no difference was found in implantation rate, clinical pregnancy rate, multiple pregnancy rate, miscarriage rate, premature delivery rate, live birth rate, and gender ratio at birth (P>0.05). The average newborn birth weight was similar in both groups (2,932.61±728.40 vs. 3,100.32±515.64 g, respectively) (P>0.05). A higher incidence of low birthweight (LBW) newborns was found in the frozen sperm group (20.91% vs. 8.49%) (P<0.05). Multiple logistic regression analysis showed that LBW is related to single or twin pregnancies (P<0.01), but not sperm (frozen or fresh) (P>0.05). We further analyzed the twin and single pregnancies in the two groups separately, and found that the incidences of LBW were both similar (P>0.05). There was no difference in the Apgar scores at 1 min and 5 min after birth between the two groups (P>0.05)., Conclusions: The use of frozen testicular sperm by TESA was efficient for men with OA. There were similar pregnancy and neonatal outcomes following TESA-ICSI using frozen or fresh sperm in this retrospective study. Prospective investigations are needed for further validation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-125/coif). The authors have no conflicts of interest to declare., (2022 Translational Andrology and Urology. All rights reserved.)

Semiconductor clusters, Zn n O n , Zn n S n , and Cd n S n (n = 2-8), were optimized and the corresponding stable structures were acquired. The symmetry, bond length, bond angle, and energy gap between HOMO and LUMO were analyzed. According to reasonable calculation and comparative analysis for small clusters Zn 2 O 2 , Zn 2 S 2 , and Cd 2 S 2 , an effective method based on density function theory (DFT) and basis set which lay the foundation for the calculation of the large clusters have been obtained. The two-photon absorption (TPA) results show that for the nano clusters with planar configuration, sizes play important role on the TPA cross section, while symmetries determine the TPA cross section under circumstance of 3D stable structures. All our conclusions provide theoretical support for the development of related experiments., (© 2022. The Author(s).)

Hepatitis B virus (HBV) belongs to Hepadnaviridae family and mainly infects hepatocytes, which can cause acute or chronic hepatitis. Currently, two types of antiviral drugs are approved for chronic infection clinically: interferons and nucleos(t)ide analogues. However, the clinical cure for chronic infection is still rare, and it is a huge challenge for all researchers to develop high-efficiency, safe, non-tolerant, and low-toxicity anti-HBV drugs. Antazoline hydrochloride is a first-generation antihistamine with anticholinergic properties, and it is commonly used to relieve nasal congestion and in eye drops. Recently, an in vitro high-throughput evaluation system was constructed to screen nearly 800 compounds from the Food and Drug Administration (FDA)-approved Drug Library. We found that arbidol hydrochloride and antazoline hydrochloride can effectively reduce HBV DNA in the extracellular supernatant in a dose-dependent manner, with EC 50 of 4.321 μmol/L and 2.910 μmol/L in HepAD38 cells, respectively. Moreover, the antiviral effects and potential mechanism of action of antazoline hydrochloride were studied in different HBV replication systems. The results indicate that antazoline hydrochloride also has a significant inhibitory effect on HBV DNA in the extracellular supernatant of Huh7 cells, with an EC 50 of 2.349 μmol/L. These findings provide new ideas for screening and research related to HBV agents.

Background:  Delay or failure of bone union is a significant clinical challenge all over the world, and it has been reported that bone marrow mesenchymal stem cells (BMSCs) offer a promising approach to accelerate bone fracture healing. Se can modulate the proliferation and differentiation of BMSCs. Se-treatment enhances the osteoblastic differentiation of BMSCs and inhibiting the differentiation and formation of mature osteoclasts. The purpose of this study was to assess the effects of porous Se@SiO 2  nanocomposite on bone regeneration and the underlying biological mechanisms. Methods:  We oxidized Se 2-  to develop Se quantum dots, then we used the Se quantum dots to form a solid Se@SiO 2  nanocomposite which was then coated with polyvinylpyrrolidone (PVP) and etched in hot water to synthesize porous Se@SiO 2  nanocomposite. We used XRD pattern to assess the phase structure of the solid Se@SiO 2  nanocomposite. The morphology of porous Se@SiO 2  nanocomposite were evaluated by scanning electron microscope (SEM) and the biocompatibility of porous Se@SiO 2  nanocomposite were investigated by cell counting kit-8 (CCK-8) assays. Then, a release assay was also performed. We used a Transwell assay to determine cell mobility in response to the porous Se@SiO 2  nanocomposite. For in vitro experiments, BMSCs were divided into four groups to detect reactive oxygen species (ROS) generation, cell apoptosis, alkaline phosphatase activity, calcium deposition, gene activation and protein expression. For in vivo experiments, femur fracture model of rats was constructed to assess the osteogenic effects of porous Se@SiO 2  nanocomposite. Results:  In vitro, intervention with porous Se@SiO 2  nanocomposite can promote migration and osteogenic differentiation of BMSCs, and protect BMSCs against H 2 O 2 -induced inhibition of osteogenic differentiation. In vivo, we demonstrated that the porous Se@SiO 2  nanocomposite accelerated bone fracture healing using a rat femur fracture model. Conclusion:  Porous Se@SiO 2  nanocomposite promotes migration and osteogenesis differentiation of rat BMSCs and accelerates bone fracture healing, and porous Se@SiO 2  nanocomposite may provide clinic benefit for bone tissue engineering., Competing Interests: The authors report no conflicts of interest in this work.

The transport and photoelectric properties of four two-dimensional (2D) silicene/MX 2 (M = Mo, W; X = S, Se) heterostructures have been investigated by employing density functional theory, nonequilibrium Green's function, and Keldysh nonequilibrium Green's function methods. The stabilities of silicene (SiE) are obviously improved after being placed on the MX 2 (M = Mo, W; X = S, Se) substrates. In particular, the conductivities of SiE/MX 2 are enhanced compared with free-standing SiE and MX 2 . Moreover, the conductivities are increased with the group number of X, i.e., in the order of SiE < SiE/MS 2 < SiE/MSe 2 . An evident current oscillation phenomenon is observed in the SiE/WX 2 heterostructures. When a linear light illumination is applied, SiE/MSe 2 shows a stronger photoresponse than SiE/MS 2 . The maximum photoresponse with a value of 9.0 a 0 2 /photon was obtained for SiE/WSe 2 . More importantly, SiE/MS 2 (M = Mo, W) heterostructures are good candidates for application in designing solar cells owing to the well spatial separation of the charge carriers. This work provides some clues for further exploring 2D SiE/MX 2 heterostructures involving tailored photoelectric properties., Competing Interests: The authors declare no competing financial interest.

The electronic, transport, and optoelectronic properties of monolayer black phosphorus (MLBP) are much influenced by grafting PdCl 2 groups, demonstrated here by using density functional theory (DFT) and non-equilibrium Green's function (NEGF) as well as the Keldysh Nonequilibrium Green's Functions (KNEGF) methods. We find that the PdCl 2 groups prefer to locate over the furrow site of MLBP and form a planar quadridentate structure of . The PdCl 2 groups serve as quantum dots by introducing discrete flat levels between the MLBP valence band and the Fermi level ( E f ). The conductivity is much lowered after attaching PdCl 2 quantum dots, due to the fact that the scattering effect of PdCl 2 plays a major role in the process of electron transporting. A threshold voltage is found for the functionalized system with a large density of PdCl 2 quantum dots, a valuable clue for exploring current switches. However, no evident threshold voltage is found for the pure MLBP. Electrons permeate easier through the armchair direction compared with the zigzag either in the pure MLBP or in the functionalized composites. More importantly, grafting PdCl 2 quantum dots is very beneficial for enhancing photoresponse. The values of photoresponse for the modified species are about 20 times higher than the free MLBP. A significant photoresponse anisotropy is observed for both MLBP and n PdCl 2 -BP ( n = 1, 2, and 4), contrary to the conductivity, the zigzag direction shows much stronger photoresponse than the armchair. All of the aforementioned unique properties make these new two-dimensional (2D) MLBP based materials especially attractive for both electronic and optoelectronic devices., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Postoperative fever is prevalent in many breast cancer patients. Some retrospective studies proposed that postoperative fever might also be considered as a rapid rough indicator for the poor prognosis of breast cancer patients. This study aims to explore the possible molecular mechanisms underlying the relapse of breast cancer patients with early postoperative fever. Our results indicated plasma levels of lncRNA MALAT1 were elevated in breast cancer patients with early postoperative fever and were associated with RFS. Lipopolysaccharide (LPS) was able to induce fever and systemic inflammatory responses in 4T1 xenograft mice, and promote lung metastasis. But after knocking down lncRNA MALAT1, the inflammatory responses and metastasis of lung were significantly reduced. Moreover, after knocking down lncRNA MALAT1 in the 4T1 cells, TNF-α level in the supernatants was sharply decreased, and the invasion and migration induced by LPS was also weakened. Cumulatively, our data indicates that MALAT1 is closely related to recurrence and metastasis of breast cancer patients with early postoperative fever., Competing Interests: None.

[This corrects the article on p. 3842 in vol. 9, PMID: 28861174.].

Objective: To investigate the anti-inflammatory effect and mechanisms of interleukin-35 (IL-35) in inflammatory bowel disease., Methods: BALB/c mice were divided into three groups with 10 mice in each group:control group, model group (oral administration of 4% glucan sodium sulfate for 7 d) and IL-35-treated group (oral administration of 4% glucan sodium sulfate for 7 d, intraperitoneal injection of 2 μg IL-35 at d2-5). Disease activity index (DAI) was scored every day. After 7 d, the mice were sacrificed, and the serum and intestinal tissue samples were collected. The gross morphology of the colon was observed; HE staining was used to observe the pathological changes of colon tissue; flow cytometry was employed to detect the change of macrophage polarization ratio in colon tissue; the mRNA expression levels of cytokines IL-6, TNF-α, IFN-γ, IL-10 and SHIP1 in colon tissue were determined by real-time quantitative RT-PCR; the expression and distribution of SHIP1 in colon tissue was measured by immunohistochemistry; Western blotting was adopted to detect the expression level of SHIP1 protein in colonic intestinal tissues of each group., Results: The DAI scores of the mice in the model group were higher than those in the control group, while the DAI scores in the IL-35-treated group were lower than those in the model group (all P <0.01). Compared with the control group, the colon length was significantly shortened in the model group ( P <0.05), while the colon length of the IL-35-treated group had an increasing trend compared with the model group, but the difference was not statistically significant ( P >0.05). Compared with the model group, microscopic inflammatory infiltration score was decreased and microscopic crypt destruction and score was significantly lower in IL-35-treated group (all P <0.05). The relative expression of proinflammatory cytokines IL-6, TNF-α and IFN-γ in the colon tissue of IL-35-treated group was decreased compared with the model group, while the relative expression of IL-10 mRNA was higher than that of the model group (all P <0.05). Compared with the control group, the proportion of M1 macrophages in the model group increased ( P <0.05), while the proportion of M1 macrophages in the IL-35-treated group was lower than that in the model group ( P <0.05). The relative expression of SHIP1 mRNA and protein in the colon tissue of IL-35-treated group was higher than that in the model group (all P <0.05)., Conclusions: IL-35 can inhibit the polarization of M1 macrophages and regulate inflammatory cytokines to promote anti-inflammatory effect on mice with colitis.

The structures, circular dichroism (CD) spectra and nonlinear optical (NLO) responses of a series of inorganic double-helix chains, PnLin (n = 6-12), have been investigated using the quantum chemistry method. P-P and P-Li interactions play a major role in stabilizing double-helix chains. The distinctive CD spectra of the double-helix frameworks (namely, a sharp negative CD band at short-wavelength region and a positive CD band at long-wavelength region) become obvious with increasing number of PLi units. The NLO response augments with the length of the double-helix chains, and the contribution of the axial component along the chain direction gradually becomes crucial simultaneously. Synergistic effects, a decrease of crucial electronic transition energies and charge transfer excitation give rise to enhanced NLO responses. In particular, the electronic transitions from the highest occupied molecular orbital to the lowest unoccupied molecular orbital make significant contributions not only to the positive CD bands in the long-wavelength region, but also to the NLO responses of the double-helix PnLin (n = 6-12) chains.

Heterotopic ossification (HO), a serious disorder of extra-skeletal bone formation, occurs as a common complication of trauma or in rare genetic disorders. Many conserved signaling pathways have been implicated in HO; however, the exact underlying molecular mechanisms for many forms of HO are still unclear. The emerging picture is that dysregulation of bone morphogenetic protein (BMP) signaling plays a central role in the process, but that other conserved signaling pathways, such as Hedgehog (HH), Wnt/β-catenin and Fibroblast growth factors (FGF), are also involved, either through cross-talk with BMP signaling or through other independent mechanisms. Deep understanding of the conserved signaling pathways is necessary for the effective prevention and treatment of HO. In this review, we update and integrate recent progress in this area. Hopefully, our discussion will point to novel promising, druggable loci for further translational research and successful clinical applications., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Heterotopic ossification (HO), acquired or hereditary, endochondral or intramembranous, is the formation of true bone outside the normal skeleton. Since perivascular Gli1+ progenitors contribute to injury induced organ fibrosis, and CD133 is expressed by a variety of populations of adult stem cells, this study utilized Cre-lox based genetic lineage tracing to test the contribution to endochondral HO of adult stem/progenitor cells that expressed either Gli1 or CD133. We found that both lineages contributed broadly to different normal tissues with distinct patterns, but that only Gli1-creERT labeled stem/progenitor cells contributed to all stages of endochondral HO in a BMP dependent, injury induced, transgenic mouse model. Hedgehog (Hh) signaling was abnormal at endochondral HO lesion sites with increased signaling surrounding the lesion but diminished signaling within it. Thus, local dysregulation of Hh signaling participates in the pathophysiology of endochondral HO. However, unlike a previous report of intramembranous HO, systemic inhibition of Hh signaling was insufficient to prevent the initiation of the endochondral HO process or to treat the existing endochondral HO, suggesting that Hh participates in, but is not essential for endochondral HO in this model. This could potentially reflect the underlying difference between intramembranous and endochondral HO. Nevertheless, identification of this novel stem/precursor cell population as a HO-contributing cell population provides a potential drugable target., (Copyright © 2017. Published by Elsevier Inc.)

Rationale: Mitochondrial dysfunction plays an important role in heart failure (HF). However, the molecular mechanisms regulating mitochondrial functions via selective mitochondrial autophagy (mitophagy) are poorly understood., Objective: We sought to determine the role of AMPK (AMP-activated protein kinase) in selective mitophagy during HF., Methods and Results: An isoform shift from AMPKα2 to AMPKα1 was observed in failing heart samples from HF patients and transverse aortic constriction-induced mice, accompanied by decreased mitophagy and mitochondrial function. The recombinant adeno-associated virus Serotype 9-mediated overexpression of AMPKα2 in mouse hearts prevented the development of transverse aortic constriction-induced chronic HF by increasing mitophagy and improving mitochondrial function. In contrast, AMPKα2 -/- mutant mice exhibited an exacerbation of the early progression of transverse aortic constriction-induced HF via decreases in cardiac mitophagy. In isolated adult mouse cardiomyocytes, AMPKα2 overexpression mechanistically rescued the impairment of mitophagy after phenylephrine stimulation for 24 hours. Genetic knockdown of AMPKα2, but not AMPKα1, by short interfering RNA suppressed the early phase (6 hours) of phenylephrine-induced compensatory increases in mitophagy. Furthermore, AMPKα2 specifically interacted with phosphorylated PINK1 (PTEN-induced putative kinase 1) at Ser495 after phenylephrine stimulation. Subsequently, phosphorylated PINK1 recruited the E3 ubiquitin ligase, Parkin, to depolarized mitochondria, and then enhanced the role of the PINK1-Parkin-SQSTM1 (sequestosome-1) pathway involved in cardiac mitophagy. This increase in cardiac mitophagy was accompanied by the elimination of damaged mitochondria, improvement in mitochondrial function, decrease in reactive oxygen species production, and apoptosis of cardiomyocytes. Finally, Ala mutation of PINK1 at Ser495 partially suppressed AMPKα2 overexpression-induced mitophagy and improvement of mitochondrial function in phenylephrine-stimulated cardiomyocytes, whereas Asp (phosphorylation mimic) mutation promoted mitophagy after phenylephrine stimulation., Conclusions: In failing hearts, the dominant AMPKα isoform switched from AMPKα2 to AMPKα1, which accelerated HF. The results show that phosphorylation of Ser495 in PINK1 by AMPKα2 was essential for efficient mitophagy to prevent the progression of HF., (© 2017 American Heart Association, Inc.)

Bone marrow contains a non-hematopoietic, clonogenic, multipotent population of stromal cells that are later called mesenchymal stem cells (MSC). Similar cells that share many common features with MSC are also found in other organs, which are thought to contribute both to normal tissue regeneration and to pathological processes such as heterotopic ossification (HO), the formation of ectopic bone in soft tissue. Understanding the microenvironmental factors that regulate MSC in vivo is essential both for understanding the biology of the stem cells and for effective translational applications of MSC. Unfortunately, this important aspect has been largely underappreciated. This review tries to raise the attention and highlight this critical issue by updating the relevant literature along with discussions of the key issues in the area.

Asiatic acid (AA), a triterpenoid derived from the medicinal plant Centella asiatica , is considered to have anti-inflammatory, anti-fibrotic and anti-tumor effects, but its effects in acute pancreatitis (AP) are unknown. Our purpose of this study was to investigate the effects of AA in a mouse model of cerulein-induced pancreatitis. We evaluated AA in an experimental model of AP induced in mice by six hourly intraperitoneal injections of cerulein 50 µg/kg. Mice were pretreated with vehicle or AA 50 mg/kg 2 h before the first cerulein injection. The severity of AP was evaluated histologically and by biochemistry, myeloperoxidase activity, proinflammatory cytokine production, and nuclear factor (NF)-κB activity. Administration of AA significantly reduced the severity of AP, and was associated with reduction of serum amylase and lipase levels, decreased pancreatic histological damage, and decreased myeloperoxidase activity. The serum levels and mRNA expression of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and NF-κB activity were reduced. AA also significantly improved the in vitro viability of pancreatic acinar cells induced by cholecystokinin (CCK) and suppressed NF-κB activity. AA protected against experimental AP, possibly by reducing production of proinflammatory cytokines via suppression NF-κB activation., Competing Interests: None.

Brucea javanica has demonstrated a variety of antitumoral, antimalarial, and anti- inflammatory properties. As a Chinese herbal medicine, Brucea javanica is mainly used in the treatment of lung and gastrointestinal cancers. Pharmacological research has identified the main antitumor components are tetracyclic triterpene quassinoids. However, most of these active components have poor water solubility and low bioavailability, which greatly limit their clinical application. Nanoparticulate delivery systems are urgently needed to improve the bioavailability of Brucea javanica. This paper mainly focuses on the chemical components in Brucea javanica and its pharmacological properties and nanoparticulate formulations, in an attempt to encourage further research on its active components and nanoparticulate drug delivery systems to expand its clinical applications. It is expected to improve the level of pharmaceutical research and provide a strong scientific foundation for further study on the medicinal properties of this plant.