Recent Developments in Nickel-Based Layered Double Hydroxides for Photo(-/)electrocatalytic Water Oxidation.

Layered double hydroxides (LDHs), especially those containing nickel (Ni), are increasingly recognized for their potential in photo(-/)electrocatalytic water oxidation due to the abundant availability of Ni, their corrosion resistance, and their minimal toxicity. This review provides a comprehensive examination of Ni-based LDHs in electrocatalytic (EC), photocatalytic (PC), and photoelectrocatalytic (PEC) water oxidation processes. The review delves into the operational principles, highlighting similarities and distinctions as well as the benefits and limitations associated with each method of water oxidation. It includes a detailed discussion on the synthesis of monolayer, ultrathin, and bulk Ni-based LDHs, focusing on the merits and drawbacks inherent to each synthesis approach. Regarding the EC oxygen evolution reaction (OER), strategies to improve catalytic performance and insights into the structural evolution of Ni-based LDHs during the electrocatalytic process are summarized. Furthermore, the review extensively covers the advancements in Ni-based LDHs for PEC OER, including an analysis of semiconductors paired with Ni-based LDHs to form photoanodes, with a focus on their enhanced activity, stability, and underlying mechanisms facilitated by LDHs. The review concludes by addressing the challenges and prospects in the development of innovative Ni-based LDH catalysts for practical applications. The comprehensive insights provided in this paper will not only stimulate further research but also engage the scientific community, thus driving the field of photo(-/)electrocatalytic water oxidation forward.

Circular RNA PRKCI (hsa_circ_0067934): a potential target in the pathogenesis of human malignancies.

Circular RNAs (circRNAs) are a new type of endogenous non-coding RNA formed by a covalent closed loop. CircRNAs are characterized by specificity, universality, conservation, and stability. They are abundant in eukaryotic cells and have biological regulatory roles at various transcriptional and post-transcriptional levels. The upregulation of circPRKCI has been observed in a variety of tumors and is directly related to the clinicopathological characteristics of tumors and prognosis. More importantly, circPRKCI can participate in the tumorigenesis, progression, recurrence, and metastasis of various tumors through many functional mechanisms, including the activation of signaling pathways, such as the phosphatidylinositol-3-kinase (PI3K)/AKT pathway, and sponging of many microRNAs (miRNAs). This review summarizes the progress achieved in understanding the biological functions of circRNA PRKCI in various tumors. The goal is to inform the discovery of more functional mechanisms and new anticancer molecular targets.

[Study of centrifuge conditions for preparing rabbit leukocyte-poor platelet-rich plasma by single centrifugation].

Objective: To explore the best centrifuge condition for preparing rabbit leukocyte-poor platelet-rich plasma (LP-PRP) by using single centrifugation method. Methods: Sixteen healthy New Zealand rabbits, aged 3-4 months, were utilized in the investigation. A total of 15 mL anticoagulated blood was extracted from the central ear artery of each rabbit, with a repeat of the blood collection procedure after 1 and 2 months. The obtained blood specimens were individually subjected to centrifugation at a radius of 16.7 cm and speeds of 1 200, 1 300, 1 400, and 1 500 r/min (equivalent to centrifugal forces of 269× g, 315× g, 365× g, and 420× g) for durations of 2, 3, 4, and 5 minutes, resulting in a total of 16 groups. Following centrifugation, collect plasma from each group to a distance of 1.5 mL from the separation plane. The volumes, platelet enrichment coefficient, and platelet recovery rates of LP-PRP in each group, under varying centrifugation conditions, were methodically computed and subsequently compared. Results: The volume of LP-PRP obtained under all centrifugation conditions ranged from 1.8 to 7.6 mL. At a consistent centrifugal speed, an extension of centrifugation time leaded to a significant increase in the volume of LP-PRP, accompanied by a declining trend in the platelet enrichment coefficient of LP-PRP. When centrifuged for 2 minutes, the volume of LP-PRP at speeds of 1 200 and 1 300 r/min was less than 2.0 mL, while the volume of LP-PRP obtained under other conditions was more than 2.0 mL. When centrifuged for 4 and 5 minutes, the volume of LP-PRP obtained at each speed was more than 4 mL. LP-PRP with a platelet enrichment coefficient more than 2.0 could be prepared by centrifuging at 1 200 r/min for each time group and 1 300 r/min for 2 and 3 minutes, and the highest LP-PRP platelet enrichment coefficient could be obtained by centrifugation for 2 minutes at a speed of 1 200 r/min. The platelet recovery rates of LP-PRP obtained by centrifugation at 1 200 r/min for 4 and 5 minutes, as well as centrifugation at 1 400 r/min for 5 minutes, were both greater than 60%. There was no significant difference between the groups when centrifuged at 1 200 r/min for 4 and 5 minutes ( P>0.05). Conclusion: In the process of preparing rabbit LP-PRP using a single centrifugation method, collecting 15 mL of blood and centrifuging at a radius of 16.7 cm and speed of 1 200 r/min for 4 minutes can prepare LP-PRP with a volume exceeding 2.0 mL, platelet enrichment coefficient exceeding 2.0, and platelet recovery rate exceeding 60%. This centrifugal condition can achieve the optimal LP-PRP action parameters in the shortest possible time.

Study on the use of 3D printed guides in the individualized reconstruction of the anterior cruciate ligament.

OBJECTIVE: Evaluation of the accuracy and effectiveness of 3D printed guides to assist femoral tunnel preparation in individualised reconstruction of the anterior cruciate ligament. METHODS: Sixty patients who attended the Affiliated Hospital of Binzhou Medical College for autologous hamstring single bundle reconstruction of the anterior cruciate ligament from October 2018 to October 2020 were selected and randomly divided into two groups, including 31 cases in the 3D printing group (14 males and 17 females, mean age 41.94 ± 10.15 years) and 29 cases in the control group (13 males and 16 females, mean age 37.76 ± 10.34 years). Patients in both groups were assessed for intraoperative femoral tunnel accuracy, the number of intraoperative positioning and the time taken to prepare the femoral tunnel, the length of the anteromedial approach incision, the pre-planned bone tunnel length and intraoperative bone tunnel length in the 3D printed group, IKDC score and Lysholm score preoperatively and at 3, 6 and 12 months postoperatively, the Lachman、pivot-shift test preoperatively and at 6 months postoperatively, gait analysis to assess internal and external rotation in flexion of the knee at 12 months postoperatively and postoperative complications in both groups. RESULTS: There was no statistical difference in functional knee scores and anteromedial approach incision length between the 3D printed and control groups (p > 0.05), while there was a statistical difference in the accuracy of tunnel positioning, the time taken to prepare the femoral bone tunnel and the degree of external rotation of the knee in flexion between the two groups (p < 0.05). There was no statistical difference between the preoperative planning of the bone tunnel length and the intraoperative bone tunnel length (p > 0.05). COMPLICATIONS: One case in the 3D printing group developed intermuscular vein thrombosis in the affected lower limb after surgery, which disappeared after treatment, while three cases in the control group developed intermuscular vein thrombosis in the affected lower limb. No complications such as bone tunnel rupture, deep vein thrombosis in the lower limb and infection occurred in either group. CONCLUSION: 3D printed guides assisted with individualized ACL reconstruction may improve the accuracy of femoral tunnel positioning, which is safe and effective, while reducing the operative time and the number of intraoperative positioning, without increasing the length of incision, and may obtain higher functional scores and rotational stability of the knee joint, which is in line with the concept of individualized ACL reconstruction.

S100A6 Activates Kupffer Cells via the p-P38 and p-JNK Pathways to Induce Inflammation, Mononuclear/macrophage Infiltration Sterile Liver Injury in Mice.

Noninfectious liver injury, including the effects of chemical material, drugs and diet, is a major cause of liver diseases worldwide. In chemical and drugs-induced liver injury, innate inflammatory responses are mediated by extracellular danger signals. The S100 protein can act as danger signals, which can promote the migration and chemotaxis of immune cells, promote the release of various inflammatory cytokines, and regulate the body's inflammatory and immune responses. However, the role of S100A6 in inflammatory response in chemical and drugs-induced sterile liver injury remains unclear. We constructed the model of sterile liver injury induced by carbon tetrachloride (CCl4)/Paracetamol (APAP) and performed RNA sequencing (RNA-seq) on the liver tissues after injury (days 2 and 5). We analyzed inflammatory protein secretion in the liver tissue supernatant by enzyme-linked immunosorbent assay (ELISA), determined the inflammation response by bioinformatic analysis during sterile liver injury, and assessed mononuclear/macrophage infiltration by immunohistochemistry and flow cytometry. Immunohistochemistry was used to analyze the location of S100A6. We conducted inflammatory factor expression analysis and molecular mechanistic studies in Kupffer cells (KCs) induced by S100A6 using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), ELISA, and western blot in vitro experiments. We performed chemokine CCL2 expression analysis and molecular mechanism studies using the same method. We used a Transwell assay to show the infiltration of mononuclear/macrophage. We here observed that aggravated inflammatory response was shown in CCl4 and APAP-administrated mice, as evidenced by enhanced production of inflammatory cytokines (TNF-α, IL-1ß), and elevated mononuclear/macrophage infiltration and activation of immunity. The expression of S100A6 was significantly increased on day 2 after sterile liver injury, which is primarily produced by injured liver cells. Mechanistic studies established that S100A6 activates Kupffer cells (KCs) via the p-P38, p-JNK and P65 pathways to induce inflammation in vitro. Furthermore, TNF-α can stimulate liver cells via the p-P38 and p-JNK pathways to produce CCL2 and promote the infiltration of mononuclear/macrophage. In summary, we showed that S100A6 plays an important role in regulating inflammation, thus influencing sterile liver injury. Our findings provide novel evidence that S100A6 can as a danger signal that contributes to pro-inflammatory activation through p-P38 and p-JNK pathways in CCl4 and APAP-induced sterile liver injury in mice. In addition, the inflammatory factor TNF-α induces a large amount of CCL2 production in normal liver cells surrounding the injured area through a paracrine action, which is chemotactic for blood mononuclear/macrophage infiltration.

Upregulated miR-322-5p regulates cell cycle and promotes cell proliferation and apoptosis by directly targeting Wee1 in mice liver injury.

Liver injury from any number of causes (e.g. chemical material, drugs and diet, viral infection) is a global health problem, and its mechanism is not clearly understood. MicroRNAs (miRNAs) expression profiling is gaining popularity because miRNAs, as key regulators in gene expression networks, can influence many biological processes and have also shown promise as biomarkers for disease. Previous studies reported the regulation effects of miRNAs in liver injury, whereas function and molecular mechanisms of miR-322-5p were still unclear. Therefore, our study focused on the biological role of miR-322-5p in carbon tetrachloride (CCl4)-induced liver injury proliferation, apoptosis, and cell cycle. A mouse model of CCl4-induced liver injury was established, and the transcriptomes and miRNAs transcriptomes of 2d and 5d liver tissues after injury were sequenced. The expression of miR-322-5p and the cell cycle genes were detected in liver tissues and Hepa1-6 cell line by miRNA RT-PCR, qRT-PCR. The effects of miR-322-5p on liver cell proliferation, cell cycle and apoptosis were evaluated using MTS assays and flow cytometry analysis. The relationship between miR-322-5p and Wee1 was predicted and confirmed by bioinformatics analysis and a dual luciferase reporter assay. Functional experiments, including an MTS assay and flow cytometric analysis, were performed to study the effects of Wee1. MiR-322-5p was upregulated in injury liver tissues, and downregulated miR-322-5p was proved to inhibit proliferation, apoptosis and arrest cell cycle at G2/M in vitro. The dual-luciferase reporter assay results indicated that miR-322-5p has a binding site at position 285 in the Wee1 3´UTR. The effects of miR-322-5p in proliferation and cell cycle regulation can be abolished by Wee1 through rescue experiments. By directly targeting Wee1 influenced the expression of several cell cycle factors, including Cyclin dependent kinase 1 (Cdk1), cyclin B1 (Ccnb1) and Cell division cyclin 25C (Cdc25C). MiR-322-5p may function as a suppressive factor by negatively controlling Wee1, thus, highlighting the potential role of miR-322-5p as a therapeutic target for liver injury.Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GSH: Glutathione, γ-glutamyl cysteinel + glycine; CCl4: Carbon tetrachloride; HE: Haematoxylin and eosin; KEGG: Kyoto Encyclopedia of Genes and Genomes.

Benefit Finding and Related Factors of Patients with Early-Stage Cancer in China.

(1) Background: Although the research on benefit finding (BF) in China has increased in recent years, it remains in its infancy. Few previous studies have focused on early-stage cancer patients. Therefore, this research study aimed to explore BF and its influencing factors for early-stage cancer patients in China. (2) Methods: From April to August 2019, 319 patients with early-stage cancer in the treatment period were selected by the convenience sampling method and evaluated using the Benefit Finding of Cancer Patients Scale-Chinese (BFS-C), Perceived Social Support Scale (PSSS), and Medical Coping Modes Questionnaire (MCMQ). (3) Results: The mean BF score was 47.57 (SD = 12.26). The results of the correlation analysis show that benefit finding was positively correlated with social support, but negatively correlated with acceptance-resignation. In addition, social support was negatively correlated with avoidance and acceptance-resignation. The results of the multiple linear regression indicate that the variables of self-assessment of disease severity, exercise time, coping mode (acceptance-resignation), and social support, affect BF. Finally, social support was shown to exert an intermediary effect on acceptance-resignation and BF. (4) Conclusions: In this study, the score of BF of patients with early-stage cancer was low. Medical staff should be more aware of the health behavior of patients with early-stage cancer, guide them to actively face the disease, and fully mobilize the social support of patients' friends and family, so as to help patients increase their disease BF.

Traditional Mongolian medicine (HHQG) attenuates CCl4-induced acute liver injury through inhibiting monocyte/macrophage infiltration via the p-P38/p-JNK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Honghua Qinggan 13 Flavor Pills (HHQG), whose Mongolian name is Guri Gumu-13, is a traditional Mongolian medicine, that was stated in the "Diagnosis and Treatment of Ming Medical Code". The HHQG has been included in the Mongolian Medicine Division of the Ministry of Health Drug Standards (1998 edition). Based on our clinical expertise, HHQG demonstrated satisfactory therapeutic effects in hepatitis and liver failure. However, the pharmacological effects and potential mechanisms of HHQG have not been investigated. AIM OF THE STUDY: In this study, we combined network pharmacology, transcriptomics, and molecular biology to detect the underlying mechanism for the effect of HHQG on acute liver injury in mice. MATERIALS AND METHODS: Network pharmacology was used to explore the pathways involved in the protective effect HHQG in acute liver injury. This effect was further verified by injecting carbon tetrachloride (CCl4; 10 mL/kg, i.p.) to induce acute liver injury in mice. Serum markers of liver injury, morphology, histology, and monocyte/macrophage infiltration in the liver tissue were investigated. Transcriptomics further defined the HHQG targets. Transwell analysis was performed to confirm that HHQG inhibited monocyte/macrophage RAW.264.7 infiltration. qPCR and Western blot were performed to explore the mechanism of action of HHQG. RESULTS: Network pharmacology showed that HHQG exerted anti-oxidative and anti-inflammatory effects and promoted metabolic effects against acute liver injury. Pretreatment of mice with HHQG significantly maintained their body weight and decreased serum tumor necrosis factor-alpha (TNF-α) levels induced by CCl4 treatment in vivo. Histopathological examination further confirmed that HHQG protected the liver cells from CCl4-induced damage. Importantly, HHQG significantly inhibited CCl4-induced monocyte/macrophage infiltration. Transcriptomic analysis revealed that HHQG significantly reduced the expression of chemokines and cell adhesion molecules. We determined that HHQG significantly downregulated the expression of the key chemokine (monocyte chemokine protein-1, CCL2) at the gene and protein levels. Further research showed that HHQG inhibited chemokine production in hepatocytes by inhibiting the p-P38 and p-JNK pathways, thereby reducing monocyte/macrophage infiltration. CONCLUSIONS: These combined data showed that HHQG alleviated acute liver injury in mice, and further verified that HHQG exerted protective effects by inhibiting the production of CCL2 and reducing the infiltration of monocyte/macrophage by inhibiting the p-P38 and p-JNK pathways.

Dynamic Compressive Behaviors of Two-Layer Graded Aluminum Foams under Blast Loading.

Experimental and numerical analyses were carried out to reveal the behaviors of two-layer graded aluminum foam materials for their dynamic compaction under blast loading. Blast experiments were conducted to investigate the deformation and densification wave formation of two-layer graded foams with positive and negative gradients. The shape of the stress waveform changed during the propagation process, and the time of edge rising was extended. Finite element models of two-layer graded aluminum foam were developed using the periodic Voronoi technique. Numerical analysis was performed to simulate deformation, energy absorption, and transmitted impulse of the two-layer graded aluminum foams by the software ABAQUS/Explicit. The deformation patterns were presented to provide insights into the influences of the foam gradient on compaction wave mechanisms. Results showed that the densification wave occurred at the blast end and then gradually propagated to the distal end for the positive gradient; however, compaction waves simultaneously formed in both layers and propagated to the distal end in the same direction for the negative gradient. The energy absorption and impulse transfer were examined to capture the effect of the blast pressure and the material gradient. The greater the foam gradient, the more energy dissipated and the more impulse transmitted. The absorbed energy and transferred impulse are conflicting objectives for the blast resistance capability of aluminum foam materials with different gradient distributions. The results could help in understanding the performance and mechanisms of two-layer graded aluminum foam materials under blast loading and provide a guideline for effective design of energy-absorbing materials and structures.

The PERK-EIF2α-ATF4 signaling branch regulates osteoblast differentiation and proliferation by PTH.

Parathyroid hormone (PTH) and its related peptide (PTH-related peptide 1-34) are two of the Food and Drug Administration-approved bone-promoting drugs for age-related osteoporosis. Treatment with PTH stimulates bone formation. However, the molecular mechanisms of PTH-mediated osteoblast differentiation and cell proliferation are still not completely understood. In this study, we showed that PTH induced endoplasmic reticulum (ER) stress in osteoblasts through the PKR-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2α (EIF2α)-activating transcription factor 4 (ATF4)-signaling pathway. After separately blocking PERK-EIF2α-ATF4 signaling with two different inhibitors [AMG'44 and integrated stress response inhibitor (ISRIB)] or specific small interfering RNA for PERK and ATF4, the following targets were all downregulated: expression of osteoblast differentiation markers [runt-related transcription factor 2 (Runx2), alkaline phosphatase (Alp), type I collagen (Col1a1), and osteocalcin (Ocn)], cell proliferation markers (CyclinE, CyclinD, and CDC2), amino acid import (Glyt1), and metabolism-related genes (Asns). Additionally, Alp-positive staining cells, Alp activity, matrix mineralization, Ocn secretion, and cell proliferation indexes were inhibited. Interestingly, we found that salubrinal enhanced PTH-induced osteoblast differentiation and proliferation by maintenance of phosphorylation of EIF2α. Furthermore, we observed that PTH increased the association between heat shock protein 90 (HSP90) and PERK and maintained PERK protein stabilization in the early stages of PTH-induced ER stress. Treatment of MC3T3-E1 cells with geldanamycin, an HSP90 inhibitor, decreased PERK protein expression and inhibited osteoblast differentiation and cell proliferation upon PTH treatment. Taken together, our data demonstrate that PTH regulates osteoblast differentiation and cell proliferation, partly by activating the HSP90-dependent PERK-EIF2α-ATF4 signaling pathway.

Lactate enhanced the effect of parathyroid hormone on osteoblast differentiation via GPR81-PKC-Akt signaling.

Osteoblast uses aerobic glycolysis to meet the metabolic needs in differentiation process. Lactate, the end product of glycolysis, presents in the environment with elevated PTH and osteoblast differentiation. Although previous findings showed that lactate promoted osteoblast differentiation, whether lactate affects PTH-mediated osteoblast differentiation is unclear. To investigate this, pre-osteoblast cell line MC3T3-E1 was treated PTH with or without physiological dose of lactate. Lactate increases ALP positive cell formation, increases ALP activity and expression of differentiation related markers, enriches the CREB transcriptional factor target genes in PTH treated cells. Using inhibitors for MCT-1 reveales that lactate effects are MCT-1 independent. Lactate selectively increases Akt and p38 activation but not Erk1/2 and ß-Catenin activation. The inhibitors for Akt and p38 inhibit lactate effects on PTH mediated osteoblast differentiation. Using inhibitors for Gαi signaling of GPR81 further increases Alp mRNA levels in lactate and PTH co-treatment cells. However, with the inhibitors for Gßγ-PLC-PKC signaling, the effect of lactate on PTH mediated osteoblast differentiation is inhibited. Our data demonstrate that lactate activates GPR81-Gßγ-PLC-PKC-Akt signaling to regulate osteoblast differentiation that mediated by PTH treatment.

Circ-PAX2 promotes proliferation and metastasis by absorbing miR-186 in lung cancer cells.

Circ-RNAs are a type of non-coding-protein RNAs which act as an effector role in many physiological processes. However, the novel function of circ-PAX2 in lung carcinomas is still unidentified. The current study is to detect the expression of circ-PAX2 in lung squamous cell carcinoma (LSCC) tissues and the physiological functions of circ-PAX2. Circ-PAX2 was distinguished in LSCC samples and matched non-tumor samples by human circRNA microarray analysis and was validated to be up-regulated in 86 specimens of LSCC tissues and lung cancer cell lines by qRT-PCR. Functional validation experiments showed that knockdown of circ-PAX2 promoted apoptosis of lung carcinoma cells, and then suppressed proliferation and migration of tumor cells. Small interfering RNA (siRNA) to circ-PAX2 inhibited growth in lung tumor cells. Bioinformatics prediction and rescue experiments showed that circ-PAX2 was a target of microRNA-186, confirmed by qRT-PCR and double luciferase reporter assay. On the whole, our findings reveal that circ-PAX2 was up-regulated and may be an oncogene in lung cancer; its function was reducing apoptosis, promoting cell proliferation and migration in lung carcinoma cells, which might be a novel therapeutic targetgene in lung cancer.

Disulfiram chelated with copper promotes apoptosis in human breast cancer cells by impairing the mitochondria functions.

Disulfiram (DSF) has been proved to have broad-spectrum anti-alcoholism effects, and it is also found to show stronger anti-tumor effects after chelating with Cu2+ to form DSF-Cu complex. In this work, we studied the anti-tumor activity of DSF-Cu in MCF-7 cells by flow cytometry, confocal laser scanning microscope, and atomic force microscopy to clarify the underlying anti-tumor mechanisms. MCF-7 cells were incubated with 50, 100, 150, 200, and 250 nM DSF chelated with 10 µM CuCl2 for 24 h. The results showed that DSF-Cu could induce the accumulation of MCF-7 cells in G2/M phase and apoptosis in a concentration-dependent manner. Additionally, atomic force microscope (AFM) analysis at nanoscale level showed that the morphology of cell was significantly shrunk with destroyed filopodia and ultrastructure presented many irregular protuberances on the cell membrane after DSF-Cu treatment, which was closely associated with the re-arrangement of cytoskeleton. DSF-Cu induced the production of reactive oxygen species (ROS), increased the concentration of intracellular Ca2+ and decreased the mitochondrial membrane potential (MMP) in MCF-7 cells resulting in a mitochondria-dependent apoptosis pathway. The results indicated that DSF-Cu has a potential anti-tumor activity in breast cancer by impairing the mitochondria functions. SCANNING 38:825-836, 2016. © 2016 Wiley Periodicals, Inc.