Search

Multistate coupled coupled neural networks (MSCCNN) and multiderivative coupled coupled neural networks (MDCCNN) are introduced in this article, and the lag outer synchronization for these two networks are tackled. First, a lag outer synchronization criterion for MSCCNN is derived using a node-based adaptive event-triggered control scheme, and the fact that the Zeno behavior does not exist is also proved. Moreover, the edge-based adaptive event-triggered control method is also utilized to address the lag outer synchronization for MSCCNN, and the existence of Zeno behavior is ruled out. In addition, two lag outer synchronization criteria for MDCCNN are given on the basis of the node- and edge-based adaptive event-triggered control strategies, and the nonexistence of Zeno behavior is also established. Finally, two examples are provided to demonstrate the feasibility of the proposed control schemes.

Background: Osteoporotic vertebral compression fracture (OVCF) has been extensively treated clinically using percutaneous vertebral augmentation (PVA), which includes percutaneous kyphoplasty and percutaneous vertebroplasty. Postoperative refracture is a common complication after PVA, but the associated factors and specific mechanisms behind these fractures are not entirely clear., Questions/purposes: In a systematic review and meta-analysis, we asked: What factors were associated with increased or decreased odds of refracture after PVA for OVCF?, Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines, we conducted a comprehensive search of the Cochrane Library, PubMed, Web of Science, and Embase for the time period from database inception to August 31, 2024 (which also was when we last searched). We included case-control studies in which participants were patients with OVCF and were treated with PVA, grouped into refracture versus non-refracture groups based on the presence or absence of refracture. We excluded studies published on preprint servers, conference reports, case reports, and systematic reviews or meta-analyses. We collected 2398 records in the database. After excluding studies that were duplicates and did not meet the inclusion criteria, we included 22 studies involving 7132 participants, 75% (5368) of whom were women, with a mean age of 76 years for patients in the refracture group and 74 years for patients in the non-refracture group. Quality assessment was performed using the Newcastle-Ottawa Scale, with which we assessed three aspects of the study; the mean ± SD score for the included studies was 7.3 ± 0.7 of 9 total (on this scale, higher scores are better), representing generally high study quality. The determination of heterogeneity relied on I2 and chi-square test, and we used a random-effects model when the I2 was > 50% and p ≤ 0.05; otherwise, a fixed-effects model was chosen. According to the Egger test and trim and fill method, publication bias did not significantly affect most of our results., Results: The combined results showed that older age (mean difference 2.24 [95% confidence interval (CI) 1.25 to 3.23]; p < 0.001), lower bone mineral density (BMD) (standardized mean difference [SMD] -0.72 [95% CI -0.99 to -0.45]; p < 0.001), greater preoperative AP vertebral height ratio (SMD 0.26 [95% CI 0.07 to 0.45]; p = 0.01), greater preoperative kyphotic angle (KA) (SMD 0.47 [95% CI 0.10 to 0.83]; p = 0.01), bone cement leakage (OR 1.39 [95% CI 1.05 to 1.84]; p = 0.02), multivertebral fractures (OR 3.58 [95% CI 2.53 to 5.07]; p < 0.001), smoking (OR 1.53 [95% CI 1.16 to 2.02]; p = 0.003), use of glucocorticoids (OR 3.18 [95% CI 2.09 to 4.84]; p < 0.001), and previous osteoporotic vertebral fracture (OR 2.55 [95% CI 1.58 to 4.13]; p < 0.001) were associated with increased odds of refractures after surgery. Use of antiosteoporosis therapy was associated with a decreased odds of postoperative refracture (OR 0.39 [95% CI 0.24 to 0.64]; p < 0.001)., Conclusion: Based on the results of our meta-analysis, surgeons can identify those who are more likely to have refracture by knowing basic information about their patients preoperatively, such as advanced age, lower BMD, greater preoperative AP ratio, greater preoperative KA, and the presence of multivertebral fractures or previous osteoporotic vertebral fracture. Also, intraoperative reduction of bone cement leakage and postoperative counseling of patients to quit smoking, reduce glucocorticoid use, and administration of antiosteoporosis therapy were used to reduce the probability of refracture. The association between some factors and refracture is uncertain, such as BMI and thoracolumbar fracture, and further studies are needed., Level of Evidence: Level III, therapeutic study., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2025 by the Association of Bone and Joint Surgeons.)

Liver cancer causes upwards of 1 million cancer deaths annually and is projected to rise by at least 55% over the next 15 years. Two of the major risk factors contributing to liver cancer have been well documented by multiple epidemiologic studies and the hepatitis B virus (HBV) and aflatoxin show a synergy that increases by more than 8-fold the risk of liver cancer relative to HBV alone. Using the population-based cancer registry established by the Qidong Liver Cancer Institute in 1972 and aflatoxin-specific biomarkers, we document that reduction of aflatoxin exposure has likely contributed to a nearly 70% decline in age-standardized liver cancer incidence over the past 30 years despite an unchanging prevalence of HBV infection in cases. A natural experiment of economic reform in the 1980s drove a rapid switch from consumption of heavily contaminated corn to minimally, if any, contaminated rice and subsequent dietary diversity. Aflatoxin consumption appears to accelerate the time to liver cancer diagnosis; lowering exposure to this carcinogen adds years of life before a cancer diagnosis. Thus, in 1990 the median age of diagnosis was 48 years, while increasing to 67 years by 2021. These findings have important translational public health implications since up to 5 billion people worldwide might be routinely exposed to dietary aflatoxin, especially in societies using corn as the staple food. Interventions against aflatoxin are an achievable outcome leading to a reduction in liver cancer incidence and years of delay of its nearly always fatal diagnosis., (© 2024 UICC.)

(1) Liver injury caused by an overdose of acetaminophen (APAP) represents a major public health concern. Paeoniflorin (PF) has been reported to have anti-inflammatory and liver-protective effects, but the underlying mechanisms remain unclear. This study aimed to investigate the effect of PF on the crosstalk between pyroptosis and NETs in AILI. (2) APAP-treated C57BL/6J mice were used to demonstrate the protective effect of PF on liver injury. HepG2 and dHL-60 cells were cultured to study the effects of PF on hepatocyte pyroptosis and neutrophil extracellular traps (NETs) in vitro. Moreover, cell co-culture experiments were performed, and mice were treated with a NETs-depleting agent and hepatocyte pyroptosis inhibitor to investigate the improvement of AILI induced by PF through regulating the crosstalk between hepatocyte pyroptosis and NETs. (3) PF significantly alleviated AILI. Additionally, PF inhibited the expression of pyroptosis-related proteins, high-mobility group box 1 (HMGB1), and NETs-associated proteins in vitro and in vivo. The co-culture experiments demonstrated that PF not only inhibited the NETs triggered by hepatocyte pyroptosis, but also suppressed the hepatocyte pyroptosis induced by NETs. In mice with depleted neutrophils, the level of hepatocyte pyroptosis notably decreased, indicating a diminished impact of PF. Similarly, NETs formation was reduced in mice receiving a pyroptosis inhibitor compared to the APAP group. Compared with DNase I alone, the reduction effect of PF combined with DNase I on serum ALT and AST levels decreased from 46.857% and 39.927% to 44.347% and 33.419%, respectively. Compared with DSF alone, PF combined with DSF reduced the ALT and AST levels from 46.857% and 39.927% to 45.347% and 36.419%, respectively. (4) PF demonstrated therapeutic effects on AILI. Its mechanism involves the regulation of the crosstalk between hepatocyte pyroptosis and NETs. This research substantiates the pharmacological promise of PF as a therapeutic intervention for acute AILI.

The Qidong Liver Cancer Institute (QDLCI) and the Qidong Cancer Registry were established in 1972 with input from doctors, other medical practitioners, and non-medical investigators arriving from urban centers such as Shanghai and Nanjing. Medical teams were established to quantify the extent of primary liver cancer in Qidong, a corn-growing peninsula on the north side of the Yangtze River. High rates of liver cancer were documented and linked to several etiologic agents, including aflatoxins. Local corn, the primary dietary staple, was found to be consistently contaminated with high levels of aflatoxins, and bioassays using this corn established its carcinogenicity in ducks and rats. Observational studies noted a positive association between levels of aflatoxin in corn and incidence of liver cancer across townships. Biomarker studies measuring aflatoxin B 1 and its metabolite aflatoxin M 1 in biofluids reflected the exposures. Approaches to decontamination of corn from aflatoxins were also studied. In 1993, investigators from Johns Hopkins University were invited to visit the QDLCI to discuss chemoprevention studies in some townships. A series of placebo-controlled clinical trials were conducted using oltipraz (a repurposed drug), chlorophyllin (an over-the-counter drug), and beverages prepared from 3-day-old broccoli sprouts (rich in the precursor phytochemical for sulforaphane). Modulation of biomarkers of aflatoxin DNA and albumin adducts established proof of principle for the efficacy of these agents in enhancing aflatoxin detoxication. Serendipitously, by 2012, aflatoxin exposures quantified using biomarker measurements documented a many hundred-fold reduction. In turn, the Cancer Registry documents that the age-standardized incidence rate of liver cancer is now 75% lower than that seen in the 1970s. This reduction is seen in Qidongese who have never received the hepatitis B vaccination. Aflatoxin mitigation driven by economic changes switched the dietary staple of contaminated corn to rice coupled with subsequent dietary diversity leading to lower aflatoxin exposures. This 50-year effort to understand the etiology of liver cancer in Qidong provides the strongest evidence for aflatoxin mitigation as a public health strategy for reducing liver cancer burden in exposed, high-risk populations. Also highlighted are the challenges and successes of international team science to solve pressing public health issues.

Based on the innate sensitivity of cell to substrate topographical cues, modulating cell-directed growth behavior is crucial for promoting tissue repair and reconstruction. Although photolithography technology has been extensively employed to fabricate a variety of anisotropic patterned structures to guide cell growth, it remains a great challenge to design high-resolution micro/nano hierarchical structures directly onto medical titanium (Ti)-based implants. Herein, we present a rapid, reliable and reproducible approach combining photolithography and hydrothermal technology to construct a micro/nano hierarchical structure including anisotropic micro-strips and a porous structure composed of TiO 2 nanotubes features. In vitro biological and physicochemical analyses revealed that the micro/nano hierarchical structures not only efficiently facilitate the localization and adsorption of BSA molecules, but also enhances the control of cell growth behavior. The synergistic effect between the physical limitation for organizing cellular cytoskeleton at micropattern and the control of focal adhesion sits at the nanoscale can effectively guide cells to maintain stable elongation and alignment, even at large micro-stripe width of 100 μm. This study presents a promising strategy to precisely construct micro/nano multi-level patterned structure on Ti substrate using biomaterials with excellent biocompatibility. These functional micro/nano hybrid micropatterns offer a powerful platform for regulating bioreagent localization and cell behaviors in various applications including tissue engineering, regenerative medicine, drug screening, and biosensors., (© 2025 Wiley Periodicals LLC.)

This paper introduces multiple state or spatial-diffusion coupled fractional-order reaction-diffusion neural networks, and discusses the outer synchronization and outer H ∞ synchronization problems for these coupled fractional-order reaction-diffusion neural networks (CFRNNs). The Lyapunov functional method, Laplace transform and inequality techniques are utilized to obtain some outer synchronization conditions for CFRNNs. Moreover, some criteria are also provided to make sure the outer H ∞ synchronization of CFRNNs. Finally, the derived outer and outer H ∞ synchronization conditions are validated on the basis of two numerical examples., 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 Ltd. All rights reserved.)

Objectives: Behçet's disease (BD) is a chronic inflammatory condition with recurrent skin lesions, uveitis, and oral and genital ulcers. Neutrophils are important in the pathogenesis of BD, but their molecular mechanisms are unclear., Methods: We performed weighted gene co-expression network analysis on the transcriptome of neutrophils from 10 BD patients and 10 healthy controls to identify hub genes and gene modules associated with BD., Results: We found eight co-expression modules with different biological functions. The turquoise module was involved in response to hydrogen peroxide and reactive oxygen species, the blue module was involved in response to external stimulus and inflammatory response, and the brown module was involved in the type I interferon signalling pathway. We further identified hub genes and transcription factors in each module by using module membership and gene significance., Conclusions: Our results reveal novel gene modules and hub genes that are associated with neutrophil activation and dysfunction in BD, which could serve as potential biomarkers and therapeutic targets for this disease.

Retinal degeneration diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), initially manifest as dysfunction or death of the retinal pigment epithelium (RPE). Subretinal transplantation of human pluripotent stem cell (hPSC)-derived RPE cells has emerged as a potential therapy for retinal degeneration. However, RPE cells differentiated from hPSCs using current protocols are xeno-containing and are rarely applied in clinical trials. The development of hPSC-derived RPE cell differentiation protocols using xeno-free biomaterials is urgently needed for clinical applications. In this study, two protocols (the activin A and NIC84 protocols) were selected for modification and use in the differentiation of hiPSCs into RPE cells; the chetomin concentration was gradually increased to achieve high differentiation efficiency of RPE cells. The xeno-free extracellular matrix (ECM) proteins, laminin-511, laminin-521 and recombinant vitronectin, were selected as plate-coating substrates, and a Matrigel (xeno-containing ECM)-coated surface was used as a positive control. Healthy, mature hPSC-derived RPE cells were transplanted into 21-day-old Royal College of Surgeons (RCS) rats, a model of retinal degeneration disease. The visual function of RCS rats was evaluated by optomotor response (qOMR) and electroretinography after transplantation of hPSC-derived RPE cells. Our study demonstrated that hPSCs can be efficiently differentiated into RPE cells on LN521-coated dishes using the NIC84 protocol, and that subretinal transplantation of the cell suspensions can delay the progression of vision loss in RCS rats., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Intrapancreatic fat deposition (IPFD) exerts a significant negative impact on patients with type 2 diabetes mellitus (T2DM), accelerates disease deterioration, and may lead to impaired β-cell quality and function., Aim: To investigate the correlation between T2DM remission and IPFD., Methods: We enrolled 80 abdominally obese patients with T2DM admitted to our institution from January 2019 to October 2023, including 40 patients with weight loss-induced T2DM remission (research group) and 40 patients with short-term intensive insulin therapy-induced T2DM remission (control group). We comparatively analyzed improvements in IPFD [differential computed tomography (CT) values of the spleen and pancreas and average CT value of the pancreas]; levels of fasting blood glucose (FBG), 2-h postprandial blood glucose (2hPBG), and insulin; and homeostasis model assessment of insulin resistance (HOMA-IR) scores. Correlation analysis was performed to explore the association between T2DM remission and IPFD., Results: After treatment, the differential CT values of the spleen and pancreas, FBG, 2hPBG, and HOMA-IR in the research group were significantly lower than those before treatment and in the control group, and the average CT value of the pancreas and insulin levels were significantly higher. Correlation analysis revealed that the greater the T2DM remission, the lower the amount of IPFD., Conclusion: T2DM remission and IPFD are inversely correlated., Competing Interests: Conflict-of-interest statement: Dr. Ma has nothing to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: This study aimed to investigate the incidence of enteral nutrition intolerance (ENI) in patients with sepsis and explore potential risk factors., Methods: A case-control study was conducted in patients with sepsis who were receiving enteral nutrition (EN) at a tertiary hospital in China. The included patients were divided into the ENI group and the non-ENI group. Univariate and multivariate analyses were performed to identify the risk factors for ENI., Results: A total of 859 patients were included in the study. Among them, 288 (33.53%) patients experienced symptoms of ENI, including diarrhea, vomiting, bloating, and gastric retention. Logistic regression analysis revealed that the Acute Physiology and Chronic Health Evaluation H (APACHE H) score, thoracocentesis, and usage of cardiotonic drugs (namely, inotropes) were independent predictors of the ENI., Conclusion: The incidence of ENI is relatively high in patients with sepsis, especially in those who have higher APACHE H scores, have undergone thoracocentesis, and have received inotropes., (© 2024. Huazhong University of Science and Technology.)

Li-rich Mn-based oxides (LRMOs) are considered as one of the most-promising cathode materials for next generation Li-ion batteries (LIBs) because of their high energy density. Nevertheless, the intrinsic shortcomings, such as the low first coulomb efficiency, severe capacity/voltage fade, and poor rate performance seriously limit its commercial application in the future. In this work, we construct successfully g-C 3 N 4 coating layer to modify Li 1.2 Mn 0.54 Ni 0.13 Co 0.13 O 2 (LMNC) via a facile solution. The g-C 3 N 4 layer can alleviate the side-reaction between electrolyte and LMNC materials, and improve electronic conduction of LMNC. In addition, the g-C 3 N 4 layer can suppress the collapse of structure and improve cyclic stability of LMNC materials. Consequently, g-C 3 N 4 (4 wt%)-coated LMNC sample shows the highest initial coulomb efficiency (78.5%), the highest capacity retention ratio (78.8%) and the slightest voltage decay (0.48 V) after 300 loops. Besides, it also can provide high reversible capacity of about 300 and 93 mAh g -1 at 0.1 and 10C, respectively. This work proposes a novel approach to achieve next-generation high-energy density cathode materials, and g-C 3 N 4 (4 wt%)-coated LMNC shows an enormous potential as the cathode materials for next generation LIBs with excellent performance., 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 Elsevier Inc. All rights reserved.)

Selenium (Se) is an essential trace element for maintaining health due to its ideal antioxidant properties. We previously prepared a new type of biogenic selenium nanoparticles based on alginate oligosaccharides (SeNPs-AOS), and this study aimed to investigate the protective effects of SeNPs-AOS (Se particle size = 80 nm, Se content = 8%) on organ health in broilers challenged with HS. A total of 192 21-day-old Arbor Acres broilers were randomly divided into four groups according to a 2 × 2 experimental design, including a thermoneutral zone group (TN, raised under 23 ± 1.5 °C); TN + SeNPs-AOS group (TN group supplemented 5 mg/kg SeNPS-AOS); HS group (HS, raised under 33 ± 2 °C for 10 h/day); and HS + SeNPs-AOS group (HS group supplemented 5 mg/kg SeNPS-AOS). There were six replicates in each group (eight broilers per replicate). The results showed that SeNPs-AOS improved the splenic histomorphology, enhanced the activity of catalase (CAT) and glutathione peroxidase (GSH-Px) of the spleen, as well as upregulating the splenic mRNA expression of antioxidant-related genes in broilers under HS. In addition, SeNPs-AOS reversed the pathological changes in bursa caused by HS increased the activity of GST, GSH-Px, and CAT and upregulated the mRNA expression of Nrf2 and antioxidant-related genes in the bursa of heat-stressed broilers. In addition, dietary SeNPs-AOS improved the hepatic damage, increased the activity of GSH-Px in the liver, and upregulated the mRNA expression of antioxidant-related genes while downregulating the Keap1 gene expression of the liver in broilers during HS. Moreover, dietary SeNPs-AOS upregulated the anti-ferroptosis-related genes expression of liver in broilers under HS. In conclusion, dietary SeNPs-AOS could relieve HS-induced oxidative damage to the spleen, bursa of Fabricius and liver in broilers by upregulating the Nrf2-mediated antioxidant gene expression and SeNPs-AOS could also upregulate the expression of hepatic Nrf2-related anti-ferroptosis genes in heat-stressed broilers. These findings are beneficial for the development of new nano-antioxidants in broilers.

Background: Mume Fructus (MF) is the fruit of Prunus mume Sieb. et Zucc, a plant of Rosaceae family. Previous studies demonstrated that MF was capable of ameliorating ulcerative colitis (UC) in mice, its action mechanism needs to be clarified., Purpose: This study deciphered whether and how MF extract accelerates colonic mucosal healing, the therapeutic endpoint of UC., Methods: Biochemical, histopathological and qRT-PCR analyses were utilized to define the therapeutic efficacy of MF on dextran sulfate sodium (DSS)-induced colitis in mice. UHPLC-QTOF-MS/MS-based metabolomics technique was adopted to explore the changes of endogenous metabolites associated with UC and responses to MF intervention. qRT-PCR analysis was performed to confirm the molecular pathway in vivo. The effects of MF and lysophosphatidylcholine (LPC) on cell viability, wound healing, proliferation, and migration were examined through a series of in vitro experiments. Moreover, the effects of different subtypes of phospholipase A2 (PLA2) inhibitors on MF-treated colonic epithelial cells were detected by wound healing test and transwell assay., Results: Orally administered MF could alleviate colitis in mice mainly by accelerating the healing of colonic mucosa. Guided by an unbiased metabolomics screen, we identified LPC synthesis as a major modifying pathway in colitis mice after MF treatment. Notably, MF facilitated the synthesis of LPC by enhancing the expression of PLA2 in colitis mice. Mechanistically, MF and LPC accelerated wound closure by promoting cell migration. Moreover, the promotion of MF on wound healing and migration of colonic epithelial cells was blunted by a cytosolic phospholipase A2 (cPLA2) inhibitor., Conclusion: MF can facilitate colonic mucosal healing of mice with colitis through cPLA2-mediated intestinal LPC synthesis, which may become a novel therapeutic agent of UC., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Layered V 10 O 24 · n H 2 O with a large interlayer spacing of 14 Å is hydrothermally synthesized and used as a cathode for potassium-ion batteries. It exhibits a capacity of 110 mA h g -1 with a capacity retention of 99.2% over 700 cycles. Its storage mechanism is identified as pseudo-capacitive intercalation.

Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide. Approximately 40% of CRC patients are KRAS sequence variation, including KRAS G13D mutation (KRAS G13D ) CRC patients, accounting for approximately 8% of all KRAS mutations in CRC patients and showing little benefit from anti-EGFR therapy. Therefore, there is an urgent need for new and effective anticancer agents in patients with KRAS G13D CRC. Here, we identified a natural product, erianin, that directly interacted with purified recombinant human KRAS G13D with a Kd of 1.1163 μM, which also significantly improve the thermal stability of KRAS G13D . The cell viability assay showed that KRAS G13D cells were more sensitive to erianin than KRAS WT or KRAS G12V cells. In vitro, results showed that erianin suppressed the migration, invasion and epithelial-mesenchymal transition (EMT) of KRAS G13D CRC cells. Furthermore, erianin induced ferroptosis, as evidenced by the accumulation of Fe 2+ and reactive oxygen species (ROS), lipid peroxidation, and changes in the mitochondrial morphology of KRAS G13D CRC cells. Interestingly, we also found that erianin-induced ferroptosis was accompanied by autophagy. Moreover, the occurrence of erianin-induced ferroptosis is reversed by autophagy inhibitors (NH4Cl and Bafilomycin A1) and ATG5 knockdown, suggesting that erianin-induced ferroptosis is autophagy-dependent. In addition, we evaluated the inhibition of tumor growth and metastasis by erianin in vivo using a subcutaneous tumor model and a spleen-liver metastasis model, respectively. Collectively, these data provide novel insights into the anticancer activity of erianin, which is valuable for the further discussion and investigation of the use of erianin in clinical anticancer chemotherapy for KRAS G13D CRC., 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 Elsevier Inc. All rights reserved.)

Background: Acetabular metastasis is a type of metastatic bone cancer, and it mainly metastasizes from cancers such as lung cancer, breast cancer, and renal carcinoma. Acetabular metastasis often causes severe pain, pathological fractures, and hypercalcemia which may seriously affect the quality of life of acetabular metastasis patients. Due to the characteristics of acetabular metastasis, there is no most suitable treatment to address it. Therefore, our study aimed to investigate a novel treatment technique to relieve these symptoms. Methods: Our study explored a novel technique to reconstruct the stability of the acetabular structure. A surgical robot was used for accurate positioning and larger-bore cannulated screws were accurately inserted under the robot's guidance. Then, the lesion was curetted and bone cement was injected through a screw channel to further strengthen the structure and kill tumor cells. Results: A total of five acetabular metastasis patients received this novel treatment technique. The data relating to surgery were collected and analyzed. The results found that this novel technique can significantly reduce operation time, intraoperative bleeding, visual analogue score scores, Eastern Cooperative Oncology Group scores, and postoperative complications (e.g., infection, implant loosening, hip dislocation) after treatment. Follow-up time ranged from 3 months to 6 months, and the most recent follow-up results showed that all patients survived and no acetabular metastasis progressed in any of the patients after surgery. Conclusion: Surgical robot-assisted tripod percutaneous reconstruction combined with the bone cement filling technique may be a novel and suitable treatment in acetabular metastasis patients. Our study may provide new insights into the treatment of acetabular metastasis., 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 © 2023 Huang, Zhu, Hu, Zhu, Xu, Ma, Wang and Zhang.)

The inflammatory cytokine IL-17A is known to have the capacity to promote osteoclastogenesis, thereby enhancing bone loss. Moreover, IL-17A can promote the expression of RANKL in osteoblasts, contributing to its pro-osteoclastogenic effect. IL-17A is an autophagy regulator, which is also responsible for its regulation on RANKL expression. However, the specific role of autophagy in IL-17A-regulated RANKL expression and the underlying mechanism of IL-17A-regulated osteoblast autophagy remain unclear. IL-17A is known to inhibit autophagy by preventing BCL2 degradation. This study aimed to explore the significance of BCL2-dependent autophagy in IL-17A-regulated RANKL expression. Our results showed that IL-17A at 50 ng/mL could inhibit autophagic activity and promote RANKL protein expression in MC3T3-E1 osteoblast line. Moreover, the corresponding concentration of IL-17A could enhance BCL2 protein expression and the protein interaction between BCL2 and Beclin1 in MC3T3-E1 cells. However, the protein expression of RANKL and BCL2 promoted by 50 ng/mL of IL-17A was blocked by autophagy activation with Beclin1 pharmacological upregulation. Furthermore, RANKL protein expression promoted by 50 ng/mL of IL-17A was also reversed by autophagy activation with BCL2 knockdown. Importantly, the supernatant from osteoblasts treated with 50 ng/mL of IL-17A made osteoclast precursors (OCPs) form larger osteoclasts, which was reversed by BCL2 knockdown in osteoblasts. In conclusion, high levels of IL-17A prevent the degradation of RANKL by inhibiting BCL2-Beclin1-autophagy activation signal transduction in osteoblasts, thereby indirectly promoting osteoclastogenesis., (© 2023. The Society for In Vitro Biology.)

Osteosarcoma is a malignant tumor that predominantly occurs in children or adolescents under the age of 20 years old. Metastasis and chemotherapy resistance are two problems in the treatment of osteosarcoma, and the lack of definite biomarkers impairs the course of treatment. In recent years, non-coding RNA, as a biomarker of osteosarcoma, has become an area of research focus. The role of long non-coding RNAs (lncRNAs), such as lncRNA OIP5-AS1, and circular RNAs, such as hsa&#95;circ&#95;0004674, in osteosarcoma have previously been revealed, and the present study investigated their clinical significance. A total of 20 samples were collected from patients with osteosarcoma. The expression levels of lncRNA OIP5-AS1 and hsa&#95;circ&#95;0004674 were analyzed in tumor tissues and patient serum, and their associations with chemotherapy sensitivity, lung metastasis and prognosis were assessed. The results revealed that these two non-coding RNAs were significantly upregulated in the osteosarcoma tissues of patients compared with those in the adjacent tumor tissues. In addition, the expression levels of the two non-coding RNAs were increased in the serum of patients with osteosarcoma compared with those in patients with bone fractures (P<0.01). In patients with lung metastasis or chemotherapy resistance (tumor necrosis rate <90%), the expression levels of the two non-coding RNAs were similarly increased. By plotting the receiver operating characteristic curve, it was revealed that the combination of hsa&#95;circ&#95;0004674 and lncRNA OIP5-AS1 was better than ALP or either non-coding RNA alone in predicting chemotherapy sensitivity and metastasis. Kaplan-Meier survival analysis showed that, in patients with osteosarcoma, higher expression of both non-coding RNAs was associated with worse survival time (log-rank test P=0.006). In conclusion, the combination of hsa&#95;circ&#95;0004674 and lncRNA OIP5-AS1 may be used as a better biomarker than traditional biomarkers, such as ALP, in a clinical setting., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Zhu et al.)

During the heterotrophic cultivation of microalgae, a cooled process against temperature rise caused by the metabolism of exogenous organic carbon sources greatly increases cultivation cost. Furthermore, microalgae harvesting is also a cost-consuming process. Cell harvesting efficiency is closely related to the characteristics of the algal cells. It may be possible to change cell characteristics through controlling culture conditions to make harvesting easier. In this study, the mesophilic Chlorella pyrenoidosa was found to be a thermal-tolerant species in the heterotrophic mode. The cells could maintain their maximal specific growth rate at 40°C and reached 1.45 day -1 , which is equivalent to that of cultures at 35°C but significantly higher than those cultured at lower temperatures. Interestingly, the cells cultured at 40°C were much easier to be harvested than those at lower temperatures. The harvesting efficiency of the cells cultured at 40°C reached 96.83% after sedimentation for 240 min, while the cells cultured at lower temperatures were reluctant to settle. Likely, the same circumstance occurred when cells were harvested by centrifugation or flocculation. The promotion of cell harvesting for cells cultured at high temperatures was mainly attributed to increased cell size and decreased cell surface charge. To the best of our knowledge, this is the first report that cells cultured at high temperatures can promote microalgae harvesting. This study explores a new approach to simplify the cultivation and harvesting of microalgae, which effectively reduces the microalgae production cost., 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 Dai, Wang, Zhu, Yang, Jiao, Sun and Wang.)

Exosomes derived from bone marrow mesenchymal stem cells can inhibit neuroinflammation through regulating microglial phenotypes and promoting nerve injury repair. However, the underlying molecular mechanism remains unclear. In this study, we investigated the mechanism by which exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation. Our in vitro co-culture experiments showed that bone marrow mesenchymal stem cells and their exosomes promoted the polarization of activated BV2 microglia to their anti-inflammatory phenotype, inhibited the expression of proinflammatory cytokines, and increased the expression of anti-inflammatory cytokines. Our in vivo experiments showed that tail vein injection of exosomes reduced cell apoptosis in cortical tissue of mouse models of traumatic brain injury, inhibited neuroinflammation, and promoted the transformation of microglia to the anti-inflammatory phenotype. We screened some microRNAs related to neuroinflammation using microRNA sequencing and found that microRNA-181b seemed to be actively involved in the process. Finally, we regulated the expression of miR181b in the brain tissue of mouse models of traumatic brain injury using lentiviral transfection. We found that miR181b overexpression effectively reduced apoptosis and neuroinflamatory response after traumatic brain injury and promoted the transformation of microglia to the anti-inflammatory phenotype. The interleukin 10/STAT3 pathway was activated during this process. These findings suggest that the inhibitory effects of exosomes derived from bone marrow mesenchymal stem cells on neuroinflamation after traumatic brain injury may be realized by the action of miR181b on the interleukin 10/STAT3 pathway., Competing Interests: None

A novel method of one-step co-cultivation and harvesting of microalgae and fungi, for efficient starch wastewater treatment and high-value biomass production was developed. By combination of Aspergillus oryzae and Chlorella pyrenoidosa, nutrients in wastewater could be converted to useful microbial biomass, while the wastewater was purified. Moreover, the microalgae C. pyrenoidosa could gradually be encapsulated in fungal pellets which promoted the biomass harvesting. The free algal cells could be completely harvested by fungal pellets within 72 h. The synergistic effects between them greatly improved the removal efficiencies of main pollutants as the removal efficiency of COD, TN, and TP reached 92.08, 83.56, and 96.58 %, respectively. In addition, the final biomass concentration was higher than that of individual cultures. The protein and lipid concentration was also significantly improved and reached 1.92 and 0.99 g/L, respectively. This study provides a simple and efficient strategy for simultaneous wastewater treatment and high-value biomass production., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A synthetic electron cyclotron emission (ECE) diagnostic is used to interpret ECE signals from preset plasma equilibrium profiles, including magnetic field, electron density, and electron temperature. According to the simulation results, the electron temperature (T e ) profile covering the harmonic overlap region can be obtained by receiving ECE signals at the high field side (HFS) of the HL-2M plasma. The third harmonic ECE at the low field side (LFS) cannot pass through the second harmonic resonance layer at the HFS unless the optical thickness (τ) of the second harmonic becomes gray (τ ≤ 2). In addition, the impact of the relativistic frequency down-shift has been evaluated and corrected. The measurable range of the HFS ECE has been calculated by scanning different parameters (electron density, temperature, and magnetic field). Higher plasma parameters allow a wider radial range of electron temperature measurements. The minimum inner measurable position can reach R = 120 cm (r/a = -0.89) when the product of core temperature (T e0 ) and density (n e0 ) is greater than 35 × 10 19  keV m -3 , which is extended by more than 30 cm inward compared with that of the LFS measurement. The HFS ECE will greatly improve the diagnostic ability of ECE systems on the HL-2M tokamak.

The present study explored the differences in active ingredients and in vitro anti-inflammatory effects of the decoction pieces by integrated processing(IPDP) and traditional processing(TPDP) of Polygoni Cuspidati Rhizoma et Radix(PCRER).The content of polydatin, resveratrol, emodin-8-O-β-D-glucoside, emodin, and physcion in IPDP and TPDP was determined by high-performance liquid chromatography(HPLC).The inflammation model was induced by lipopolysaccharide(LPS) in RAW264.7 cells.The mRNA levels of inflammatory cytokines tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1β(IL-1β) in 60% ethanol extracts of IPDP and TPDP of different concentrations(5 and 10 μg·mL~(-1)) were determined by PCR.The results showed that the content of polydatin and emodin-8-O-β-D-glucoside in IPDP was significantly higher than that in TPDP, while the content of resveratrol, emodin, and physcion was higher in TPDP.The anti-inflammatory results showed that ethanol extracts of IPDP of different concentrations(5 and 10 μg·mL~(-1)) significantly inhibited the increase in the mRNA levels of IL-1β and TNF-α induced by LPS, whereas TPDP only had a significant inhibitory effect on IL-1β.This study preliminarily showed that the total content of five active ingredients in IPDP was higher than that in TPDP, and IPDP was superior to TPDP in anti-inflammatory activity in vitro, which provided an experimental basis for the production and application of IPDP.

Background: In diet-induced arterial atherosclerosis, increased KCa3.1 channel was associated with atherosclerotic plaque progression and instability. Macrophages are involved in the formation of atherosclerotic plaques, and the release of inflammatory cytokines and oxygen free radicals promotes plaque progression. However, whether the macrophage KCa3.1 channel facilitates diabetes-accelerated atherosclerosis is still unclear. This study investigated atherosclerotic plaque in ApoE -/- mice regulated by the KCa3.1 channel., Methods and Results: In vivo, blocking KCa3.1channel inhibit the development of the atherosclerotic lesion in diabetic ApoE -/- mice fed with a high-fat diet. In vitro, upregulation of KCa3.1 channel level occurred in RAW264.7 cells treated with HG plus ox-LDL in a time-dependent manner. Blocking KCa3.1 significantly reduced the uptake of ox-LDL in mice peritoneal macrophages. Further studies indicated the KCa3.1 siRNA and TRAM-34 (KCa3.1 inhibitor) attenuated the scavenger receptor CD36 expression via inhibiting STAT3 phosphorylation., Conclusion: Blockade of macrophage KCa3.1 channel inhibit cellular oxidized low-density lipoprotein accumulation and decrease proinflammation factors expression via STAT3/CD36 axis. This study provided a novel therapeutic target to reduce the risk of atherosclerosis development in diabetic patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Sustained activation of multiple receptor tyrosine kinases (RTKs) simultaneously is vital for tumorigenesis and progression of osteosarcoma (OS). Gαi proteins recruitment to various RTKs mediates downstream oncogenic signaling activation. The expression, functions and underlying mechanisms of Gαi3 in human OS were examined. Expression of Gαi3 is robustly elevated in human OS tissues and is correlated with a poor overall survival. In patient-derived primary OS cells and immortalized lines (MG63 and U2OS), Gαi3 depletion, by shRNA and CRISPR/Cas9 strategies, robustly suppressed cell viability, proliferation and migration, while provoking G1-S arrest and apoptosis activation. Conversely, Gαi3 overexpressing ectopically can accelerate proliferation and migration of OS cells. In OS cells, Gαi3 immunoprecipitated with VEGFR2, FGFR, PGDFR and EGFR, mediating downstream cascade transduction. Akt-mTOR activation in primary OS cells was potently inhibited by Gαi3 shRNA, knockout or dominant negative mutation, but augmented after Gαi3 overexpression. In vivo studies showed that Gαi3 shRNA AAV (adeno-associated viruses) intratumoral injection largely inhibited the growth of subcutaneous xenografts of primary OS cells. Moreover, the growth of the Gαi3-knockout primary OS xenografts was much slower than that of OS xenografts with empty vector. In Gαi3-depleted OS xenografts tissues, Gαi3 downregulation and Akt-mTOR inactivation were detected. Taken together, overexpressed Gαi3 mediates RTK-Akt signaling to drive OS progression., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

With the rapid aging of the population, coronary artery disease (CAD) has become one of the most fatal chronic diseases. However, the genetic mechanism of CAD is still unclear. The purpose of this study is to construct the lncRNA-miRNA-mRNA regulatory network for CAD diseases and systematically identify differentially expressed genes in patients with coronary heart disease. In this study, two lncRNA datasets (GSE69587 and GSE113079) and a microRNA dataset (GSE105449) which contained 393 and 38 CAD samples were selected. In addition, two mRNA datasets which named GSE113079 (98 CAD samples) and GSE9820 (8 CAD samples) were selected to search the differentially expressed genes (DEGs). By comparing the expression data between CAD and control samples, a total of 1111 lncRNAs, 2595 mRNAs and 22 miRNAs were identified. Based on the DEGs, a lncRNA-miRNA-mRNA ceRNA network was constructed to explore the hub nodes in CAD. In the ceRNA network, the lncRNAs KCNQ1OT1 and H19 showed high connectivity with the nine miRNAs. GO and KEGG results showed that genes in ceRNA networks were mainly involved in nitrogen compound metabolic process, PI3K-Akt signaling pathway and retrograde endocannabinoid signaling. These findings will improve the understanding of the occurrence and development mechanism of CAD., (© 2021. The Author(s).)

POLRMT (RNA polymerase mitochondrial) is essential for transcription of mitochondrial genome encoding components of oxidative phosphorylation process. The current study tested POLRMT expression and its potential function in osteosarcoma (OS). The Cancer Genome Atlas (TCGA) cohorts and Gene Expression Profiling Interactive Analysis (GEPIA) database both show that POLRMT transcripts are elevated in OS tissues. In addition, POLRMT mRNA and protein levels were upregulated in local OS tissues as well as in established and primary human OS cells. In different OS cells, shRNA-induced stable knockdown of POLRMT decreased cell viability, proliferation, migration, and invasion, whiling inducing apoptosis activation. CRISPR/Cas9-induced POLRMT knockout induced potent anti-OS cell activity as well. Conversely, in primary OS cells ectopic POLRMT overexpression accelerated cell proliferation and migration. In vivo, intratumoral injection of adeno-associated virus-packed POLRMT shRNA potently inhibited U2OS xenograft growth in nude mice. Importantly, levels of mitochondrial DNA, mitochondrial transcripts and expression of respiratory chain complex subunits were significantly decreased in U2OS xenografts with POLRMT shRNA virus injection. Together, POLRMT is overexpressed in human OS, promoting cell growth in vitro and in vivo. POLRMT could be a novel therapeutic target for OS., (© 2021. The Author(s).)

To evaluate the ameliorative effect of algae-derived polysaccharide (ADP) supplementation on duodenal injury caused by heat stress (HS) in broilers, a total of 144 male yellow-feathered broilers (56-day-old) were randomly allocated into three groups: The TN group (thermoneutral zone, broilers were raised at 23.6 ± 1.8 °C); HS group (heat stress, broilers were exposed to 33.2 ± 1.5 °C 10 h/day, 8:00 a.m.-18:00 p.m., the temperature in the remaining period was consistent with the TN group); HSA group (heat-stressed broilers were fed with ADP supplemented diet at 1000 mg/kg). There were six replications in each treatment, and eight broilers in each replication. The feeding trial lasted four weeks. The results showed that dietary ADP supplementation tended to increase the villus height ( p = 0.077) and villus width ( p = 0.062), and decrease the apoptosis rate ( p = 0.081) in the duodenum of broilers under HS. Furthermore, dietary ADP increased the relative mRNA and protein (based on immunofluorescence) expression levels of occludin and zonula occludens-1 (ZO-1) in the duodenum of broilers under HS ( p < 0.05). In addition, dietary ADP enhanced the total antioxidation capacity (T-AOC) and activity of glutathione-S transferase (GST), while reducing the malondialdehyde (MDA) concentration of the duodenum in broilers under HS ( p < 0.05). Moreover, dietary ADP supplementation upregulated the duodenal nuclear factor erythroid 2-related factor 2 ( Nrf2 ), heme oxygenase-1 ( HO-1 ), glutathione peroxidase 1 ( GPx1 ) and glutathione S-transferase theta 1 ( GSTT1 ) mRNA expression levels in heat-stressed broilers ( p < 0.05). Furthermore, compared with the HS group, broilers fed with an ADP supplemented diet had a higher relative mRNA expression of inhibitor kappa B alpha ( IκBα ) ( p < 0.05) and a lower relative mRNA expression of tumor necrosis factor-α ( TNF-α ) and interleukin-1β ( IL-1β ) in the duodenum ( p < 0.05). In summary, dietary ADP supplementation had an ameliorative effect on HS-induced impairment of tight junctions, antioxidant capacity and the immune response of the duodenum in broilers. These beneficial effects might be related to the modulation of Nrf2 and NF-κB signaling pathways.

The carbon-coated LiMn 0.5 Fe 0.5 PO 4 @Li 0.33 La 0.56 TiO 3 nanorod composites (denoted as C/LMFP@LLTO) have been successfully obtained according to a common hydrothermal synthesis following a post-calcination treatment. The morphology and particle size of LiMn 0.5 Fe 0.5 PO 4 (denoted as LMFP) are not changed by the coating. All electrode materials exhibit nanorod morphology; they are 100-200 nm in length and 50-100 nm in width. The Li 0.33 La 0.56 TiO 3 (denoted as LLTO) coating can facilitate the charge transfer to enhance lithiation/delithiation kinetics, leading to an excellent rate performance and cycle stability of an as-obtained C/LMFP@LLTO electrode material. The reversible discharge capacities of C/LMFP@LLTO (3 wt %) at 0.05 and 5 C are 146 and 131.3 mA h g -1 , respectively. After 100 cycles, C/LMFP@LLTO (3 wt %) exhibits an outstanding capacity of 106.4 mA h g -1 with an 81% capacity retention rate at 5 C, indicating an excellent reversible capacity and good cycle capacity. Therefore, it can be considered that LLTO coating is a prospective pathway to exploit the electrochemical performances of C/LMFP.

Osteosarcoma (OS) is a common primary bone malignancy. We here investigated the potential activity of PF-06409577, a novel, potent, and direct activator of AMP-activated protein kinase (AMPK), against human OS cells. In established (U2OS, MG-63, and SaOs-2 lines) and primary human OS cells, PF-06409577 inhibited cell viability and proliferation, while inducing cell apoptosis and cell cycle arrest. PF-06409577 induced AMPK activation, mTORC1 inhibition, autophagy induction, and downregulation of multiple receptor tyrosine kinase inOS cells. AMPK inactivation by AMPK α 1 shRNA, CRISPR/Cas9 knockout, or dominant negative mutation (T172A) was able to abolish PF-06409577-induced activity in OS cells. In vivo , PF-06409577 oral administration at well-tolerated doses potently inhibited growth of U2OS cells and primary human OS cells in severe combined immunodeficient mice. AMPK activation, mTORC1 inhibition, autophagy induction, as well as RTK degradation and apoptosis activation were detected in PF-06409577-treated xenografts. In conclusion, activation of AMPK by PF-06409577 inhibits OS cell growth., 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 © 2021 Zhu, Zhang, Wu, Yu, Liu and Zhang.)

Na2Li2Ti6O14 particles were prepared by a simple solid-state process, and then g-C3N4-coated Na2Li2Ti6O14 composites were constructed by a facile solution route for the first time. The g-C3N4-coated Na2Li2Ti6O14 multicomponent composites because of their unique architecture as negative materials for Li-ion batteries can be expected to exhibit a significantly improved cycling stability and reversible capacity even at high rates. g-C3N4 (5 wt%)-coated Na2Li2Ti6O14 shows a discharge (charge) capacity of 184.4 (184.3) mA h g-1 at 500 mA g-1 after 100 cycles, which is larger than that of pristine Na2Li2Ti6O14 with a discharge (charge) capacity of 122.8 (122.0) mA h g-1. The use of g-C3N4 with a carbon framework containing abundant nitrogen provides more active sites and surface defects for redox reactions and Li-ion transport. The g-C3N4 coating decreases the impedance between the electrolyte and Na2Li2Ti6O14 and enhances the charge transfer, ionic conductivity and diffusion ability of Li ions of Na2Li2Ti6O14. This work offers an efficient way to design high-performance Na2Li2Ti6O14-based materials for advanced lithium ion battery, and g-C3N4 (5 wt%)-coated Na2Li2Ti6O14 shows an enormous potential as a negative material for next generation Li-ion batteries with excellent performance.

Abstract: This retrospective study aimed to explore the effect of orthodontic treatment (ODT) on anterior tooth displacement (ATD) caused by periodontal disease (PD).A total of 72 patients were selected and were divided into a control group (n = 36) and an experimental group (n = 36). Patients in both groups received conventional periodontal treatment. In addition, patients in the experimental group also received ODT. Outcomes include probing depth, percentage of bleeding sites, clinical attachment loss, clinical crown length, tooth root length, and periodontal tissue of the affected tooth (alveolar bone height, periodontal pocket depth, bleeding index).After treatment, the patients in the experimental group achieved more improvements in probing depth (P < .01), percentage of bleeding sites (P < .01), clinical attachment loss (P < .01), clinical crown length (P = .04), and periodontal tissue of the affected tooth (periodontal pocket depth (P < .01), and bleeding index (P < .01)), than those of patients in the control group.This study suggests that ODT is beneficial for ATD caused by PD. Future studies are still needed to verify the findings of this study., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

HBO1 (KAT7 or MYST2) is a histone acetyltransferase that acetylates H3 and H4 histones. Methods: HBO1 expression was tested in human OS tissues and cells. Genetic strategies, including shRNA, CRISPR/Cas9 and overexpression constructs, were applied to exogenously alter HBO1 expression in OS cells. The HBO1 inhibitor WM-3835 was utilized to block HBO1 activation. Results: HBO1 mRNA and protein expression is significantly elevated in OS tissues and cells. In established (MG63/U2OS lines) and primary human OS cells, shRNA-mediated HBO1 silencing and CRISPR/Cas9-induced HBO1 knockout were able to potently inhibit cell viability, growth, proliferation, as well as cell migration and invasion. Significant increase of apoptosis was detected in HBO1-silenced/knockout OS cells. Conversely, ectopic HBO1 overexpression promoted OS cell proliferation and migration. We identified ZNF384 (zinc finger protein 384) as a potential transcription factor of HBO1. Increased binding between ZNF384 and HBO1 promoter was detected in OS cell and tissues, whereas ZNF384 silencing via shRNA downregulated HBO1 and produced significant anti-OS cell activity. In vivo , intratumoral injection of HBO1 shRNA lentivirus silenced HBO1 and inhibited OS xenograft growth in mice. Furthermore, growth of HBO1-knockout OS xenografts was significantly slower than the control xenografts. WM-3835, a novel and high-specific small molecule HBO1 inhibitor, was able to potently suppressed OS cell proliferation and migration, and led to apoptosis activation. Furthermore, intraperitoneal injection of a single dose of WM-3835 potently inhibited OS xenograft growth in SCID mice. Conclusion: HBO1 overexpression promotes OS cell growth in vitro and in vivo., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background and Aims: Liver cancer is one of the most dominant malignant tumors in the world. The trends of liver cancer mortality over the past six decades have been tracked in the epidemic region of Qidong, China. Using epidemiological tools, we explore the dynamic changes in age-standardized rates to characterize important aspects of liver cancer etiology and prevention., Methods: Mortality data of liver cancer in Qidong from 1958 to 1971 (death retrospective survey) and from 1972 to 2017 (cancer registration) were tabulated for the crude rate (CR), and age-standardized rate and age-birth cohorts. The average annual percentage change was calculated by the Joinpoint Regression Program., Results: The natural death rate during 1958-2017 decreased from 9‰ to 5.4‰ and then increased to 8‰ as the population aged; cancer mortality rates rose continuously from 57/10 5 to 240/10 5 . Liver cancer mortality increased from 20/10 5 to 80/10 5 , and then dropped to less than 52/10 5 in 2017. Liver cancer deaths in 1972-2017 accounted for 30.53% of all cancers, with a CR of 60.48/10 5 , age-standardized rate China (ASRC) of 34.78/10 5 , and ASRW (world) of 45.71/10 5 . Other key features were the CR for males and females of 91.86/10 5 and 29.92/10 5 , respectively, with a sex ratio of 3.07:1. Period analysis showed that the ASRs for mortality of the age groups under 54 years old had a significant decreasing trend. Importantly, birth cohort analysis showed that the mortality rate of liver cancer in 40-44, 35-39, 30-34, 25-29, 20-24, 15-19 years cohort decreased considerably, but the rates in 70-74, and 75+ increased., Conclusions: The crude mortality rate of liver cancer in Qidong has experienced trends from lower to higher levels, and from continued increase at a high plateau to most recently a gradual decline, and a change greatest in younger people. Many years of comprehensive prevention and intervention measures have influenced the decline of the liver cancer epidemic in this area. The reduction of intake levels of aflatoxin might be one of the most significant factors as evidenced by the dramatic decline of exposure biomarkers in this population during the past three decades., Competing Interests: The authors declare there are no competing interests., (©2021 Chen et al.)

Considering Hengshui Lake as the research object, the representative surface sediments at eleven points were collected in March 2019, and the morphological distribution characteristics of carbon, nitrogen, and phosphorus nutrients in the lake sediments were analyzed. The results showed that the total organic carbon (TOC) content in Hengshui Lake sediments was 93.226 mg·g -1 , which might lead to a higher risk of potential nitrogen source release. The total nitrogen (TN) content was 1.850 mg·g -1 , which was a moderate pollution load; the contents of various nitrogen forms and the proportions in TN were Res-N (0.973 mg·g -1 , 52.57%) > WAEF-N (0.531 mg·g -1 , 28.69%) > SOEF-N (0.208 mg·g -1 , 11.23%) > IEF-N 0.088 (mg·g -1 , 4.77%) > SAEF-N (0.051 mg·g -1 , 2.75%). These results further indicated that the risk of nitrogen release from sediments in Hengshui Lake was relatively high. The content of total phosphorus (TP) was 1.020 mg·g -1 and that of inorganic phosphorus (IP) was 0.839 mg·g -1 , accounting for 82.27% of the TP content, which was a moderate pollution load; the average content of various phosphorus forms and the proportions in IP were Ca-P (0.440 mg·g -1 , 52.44%) > Res-P (0.200 mg·g -1 , 23.84%) > Fe-P and Al-P (0.169 mg·g -1 , 20.14%) > NH 4 Cl-P (0.030 mg·g -1 , 3.58%). In general, the risk of phosphorus release from sediments in Hengshui Lake was relatively low. The analysis of C/N, C/P, and N/P characteristics showed that the organic matter in Hengshui Lake sediments mainly originated from terrestrial grasses and sedge plants, and the phosphorus in the sediments was mainly affected by terrestrial input. Correlation analysis showed that the correlation between carbon, nitrogen, and phosphorus in Hengshui Lake sediment was weak, and the sources of the three nutrients might be different; the correlation between each form of phosphorus was stronger than that of each form of nitrogen, and each form of phosphorus had very good homology. The sources of various forms of nitrogen were diverse and complex. The pollution status of the lake area was evaluated by organic index and organic nitrogen. The results showed that the nutrient pollution in Hengshui Lake sediments was serious, reaching the Grade Ⅳ standard. The potential risk of nitrogen in sediments should be taken seriously and effectively controlled.

Non-small-cell lung carcinoma (NSCLC) accounts for approximately 80% of lung cancers with a high metastatic potential. Elucidating the mechanism of NSCLC metastasis will provide new promising targets for NSCLC therapy and benefit its prognosis. Plasmacytoma variant translocation 1 (PVT1) has been proven to be overexpressed in NSCLC. Although the oncogenic role of PVT1 in NSCLC has been reported, its mechanism remains unclear. Here, we verified that the knockdown of PVT1 inhibited NSCLC cell migration and invasion, and that its inhibitory role on A549 cells and H1299 cells was antagonized by interleukin-6 (IL-6) treatment. The results revealed that PVT1 regulates IL-6 by sponging miR-760 and identified the binding site of miR-760 in the 3'-UTR of IL-6. In conclusion, a new mechanism was revealed, wherein PVT1 regulates NSCLC cell migration and invasion via miR-760/IL-6, suggesting PVT1/miR-760/IL-6 as promising prognostic biomarkers and therapeutic targets for NSCLC metastasis., (Copyright © 2020. Published by Elsevier Ltd.)

In situ electrochemical activation as a new pretreating method to adjust electrocatalytic performance attracts extensive attention. However, the activation mechanisms of electrocatalysts are still ambiguous. Herein, we propose a facile modulation strategy of in situ cathodic activation of FeP x based on W-incorporation (W-FeP x /IF) for the hydrogen evolution reaction (HER). The activated W-FeO x with obvious surface reconstruction demonstrates the role of W-incorporation for driving the cathodic activation of FeP x , which suggests the larger surface area and more active sites. In fact, W incorporation can not only accelerate the cathodic activation process but also act as the adsorption sites for H ad to form the synergistic effect with FeO x for water dissociation. The obtained W-FeO x /IF exhibits greatly enhanced HER activity featuring decreased overpotential from 237.7 to 154.0 mV at 100 mA cm -2 , which may be ascribed to W-FeO x with double catalytic active sites after cathodic activation. Additionally, the modulation effects of cathodic activation can be exactly achieved by changing electrochemical parameters such as CV cycles. W-FeO x /IF also shows excellent long-term stability for at least 100 h at 100 mA cm -2 . This modulation engineering based on metal doping is expected to provide inspiration for the understanding of the cathodic activation process for efficient electrocatalysts.

In this work, a rational design and construction of porous spherical NiO@NiMoO 4 wrapped with PPy was reported for the application of high-performance supercapacitor (SC). The results show that the NiMoO 4 modification changes the morphology of NiO, and the hollow internal morphology combined with porous outer shell of NiO@NiMoO 4 and NiO@NiMoO 4 @PPy hybrids shows an increased specific surface area (SSA), and then promotes the transfer of ions and electrons. The shell of NiMoO 4 and PPy with high electronic conductivity decreases the charge-transfer reaction resistance of NiO, and then improves the electrochemical kinetics of NiO. At 20Ag -1 , the initial capacitances of NiO, NiMoO 4 , NiO@NiMoO 4 and NiO@NiMoO 4 @PPy are 456.0, 803.2, 764.4 and 941.6Fg -1 , respectively. After 10,000 cycles, the corresponding capacitances are 346.8, 510.8, 641.2 and 904.8Fg -1 , respectively. Especially, the initial capacitance of NiO@NiMoO 4 @PPy is 850.2Fg -1 , and remains 655.2Fg -1 with a high retention of 77.1% at 30Ag -1 even after 30,000 cycles. The calculation result based on density function theory shows that the much stronger Mo-O bonds are crucial for stabilizing the NiO@NiMoO 4 composite, resulting in a good cycling stability of these materials., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2020 Science China Press. Published by Elsevier B.V. All rights reserved.)

Vascular dysfunction resulting from diabetes is an important factor in arteriosclerosis. Previous studies have shown that during hyperglycaemia and diabetes, AKAP150 promotes vascular tone enhancement by intensifying the remodelling of the BK channel. However, the interaction between AKAP150 and the BK channel remains open to discussion. In this study, we investigated the regulation of impaired BK channel-mediated vascular dysfunction in diabetes mellitus. Using AKAP150 null mice (AKAP150 -/- ) and wild-type (WT) control mice (C57BL/6J), diabetes was induced by intraperitoneal injection of streptozotocin. We found that knockout of AKAP150 reversed vascular remodelling and fibrosis in mice with diabetes and in AKAP150 -/- diabetic mice. Impaired Akt/GSK3β signalling contributed to decreased BK-β 1 expression in aortas from diabetic mice, and the silencing of AKAP150 increased Akt phosphorylation and BK-β 1 expression in MOVAS cells treated with HG medium. The inhibition of Akt activity caused a decrease in BK-β 1 expression, and treatment with AKAP150 siRNA suppressed GSK3β expression in the nuclei of MOVAS cells treated with HG. Knockout of AKAP150 reverses impaired BK channel-mediated vascular dysfunction through the Akt/GSK3β signalling pathway in diabetes mellitus., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Sphingosine kinase 1 (SphK1) is a potential therapeutic target for human osteosarcoma (OS). SphK1-targeting microRNAs (miRNAs) could have important therapeutic value for OS. We discovered that micorRNA-3677 (miR-3677) is a SphK1-targeting miRNA, inhibiting OS cell progression. The results of RNA-Pull down assay confirmed direct binding between biotinylated-miR-3677 and SphK1 mRNA in primary human OS cells. In established and primary human OS cells forced overexpression of miR-3677, by a lentiviral construct, decreased SphK1 3'-UTR (untranslated region) activity and downregulated SphK1 expression. Both were however enhanced with miR-3677 inhibition in OS cells. Function studies demonstrated that OS cell growth, proliferation and migration were inhibited with miR-3677 overexpression, but augmented with miR-3677 inhibition. MiR-3677 overexpression-induced anti-OS cell activity was reversed with re-expression of the 3'-UTR-depleted SphK1 . Additionally, in SphK1 knockout OS cells (by CRISPR/Cas9 strategy), altering miR-3677 expression failed to further alter cell functions. Finally, we show that miR-3677 expression was significantly downregulated in primary human OS tissues, correlating with SphK1 mRNA upregulation. We conclude that targeting SphK1 by miR-3677 inhibits human OS cell progression.