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Purpose To quantitatively assess and compare the clinical outcomes, including survival rate, success rate, and peri-implant indices of titanium and zirconium implants in randomized controlled trials. Methods The electronic databases searched included the Cochrane Central Register of Controlled Trials (CENTRAL), Medline via Ovid, EMBASE, and Web of Science. Randomized controlled trials (RCTs) that reported the effects of zirconium implants on primary outcomes, such as survival rate, success rate, marginal bone loss (MBL), and probing pocket depth (PPD), compared to titanium implants were included in this review. Two reviewers independently screened and selected the records, assessed their quality, and extracted the data from the included studies. Results A total of four studies from six publications reviewed were included. Two of the comparative studies were assessed at minimal risk of bias. Zirconium implants may have a lower survival rate (risk ratio (RR) = 0.91, CI [0.82–1.02], P = 0.100, I2 = 0%) and a significantly lower success rate than titanium implants (RR = 0.87, CI [0.78–0.98], P = 0.030, I2 = 0%). In addition, there was no difference between the titanium and zirconium implants in terms of MBL, PPD, bleeding on probing (BOP), plaque index (PI), and pink esthetic score (PES) (for MBL, MD = 0.25, CI [0.02–0.49], P = 0.033, I2 = 0%; for PPD, MD = −0.07, CI [−0.19–0.05], P = 0.250, I2 = 31%). Conclusion Zirconium implants may have higher failure rates due to their mechanical weakness. Zirconium implants should be strictly assessed before they enter the market. Further studies are required to confirm these findings.

Developing rubber agroforestry systems is crucial to ensure the sustainable development of natural rubber cultivation. This study focuses on the starch crop Maranta arundinacea (arrowroot) and assesses its productivity and influencing factors when intercropped in 6–7-year-old conventional single-row and double-row rubber plantations. We analyze various aspects, including light resources, root distribution, soil nutrients, arrowroot growth characteristics, and product quality. The results indicate that the daily average photosynthetically active radiation (PAR) in the double-row rubber agroforestry system intercropping area ranges from 896.4 to 940.2 μmol·m−2·s−1. Additionally, the rubber tree roots near the intercropping area are less dense (107.0 g cm−3). In contrast, the conventional single-row rubber agroforestry system has a significantly lower daily average PAR of only 145.7 μmol·m−2·s−1, and the nearby rubber tree roots are more abundant (616.2 g cm−3). Although soil nutrient levels were slightly lower in the intercropping area on the double-row treatment compared to the single-row treatment, there was no statistical difference (p < 0.05). Arrowroot’s photosynthetic capacity in the double-row rubber agroforestry system intercropping area is significantly greater than in the single-row rubber agroforestry system intercropping area. The yield per unit area in the former (23.46–27.47 t·ha−1) is also significantly higher than in the latter (2.87–4.75 t·ha−1, p < 0.05), with higher starch content. Therefore, arrowroot exhibits higher productivity when intercropped in double-row rubber agroforestry systems, making it suitable for establishing a “rubber–arrowroot” agroforestry model to enhance the yield per unit area of rubber plantations.

In this study, copper slag and low-grade nickel laterite were synergistically utilized via an innovative sintering process with multi-force fields. Their sintering performance and the reduction and softening dripping characteristics of Fe–Ni–Cu product sinter were determined. The strengthening mechanism of the innovative sintering technology was revealed. The obtained Fe–Ni–Cu alloy and smelting slag from the melting dripping process were characterized. Carbon emissions reduction and other valuable elements treatment were also discussed. Due to the formation of the denser sinter microstructure and the reduction of high smelting components, sintering performances in the innovative sintering process are substantially improved. Compared with the base case, tumble index and productivity are improved by 24.87% and 19.59%, respectively. Solid fuel consumption is reduced by 27.14%. The reduction and softening dripping characteristics of Fe–Ni–Cu product sinter are excellent as well. The obtained Fe–Ni–Cu alloy with high purity can be used as the high-quality burden for copper-bearing stainless steel and high-strength alloy steel and its quality can be further improved by optimizing the smelting process parameters in the near future. In addition, the obvious carbon emissions reduction in sintering-blast furnace production can be achieved and other valuable elements such as S, Zn and Pb can be conveniently recycled in form of sulphuric acid and Pb–Zn dust, respectively.

Modulating single-metal sites at the atomic level can boost the intrinsic catalytic activity. Here, the authors describe the design of Pt atomic clusters containing Pt-O-Pt units supported on Co single atoms and N co-doped carbon for enhanced hydrogen evolution catalysis.

Background/purpose: Patients receiving antithrombotic drugs are more likely to suffer bleeding after tooth extraction and multiple factors are related to it. The aim of this study was to investigate the incidence of bleeding and risk factors for bleeding after dental extractions in patients receiving antithrombotic drugs. Materials and methods: This retrospective case control study included patients receiving oral antithrombotic drugs or not. Tooth extractions were conducted under ECG monitoring and local hemostatic measures were performed. Risk factors for postoperative hemorrhage after tooth extraction were evaluated using univariate and multivariate analyses. Results: Bleeding events were reported in 27 (27%) patients receiving antithrombotic drugs and 9 (9%) patients who didn't use antithrombotic drugs, the difference between which was significant (p 75 years), oral hygiene, inferior nerve block and number of extracted tooth may be related to bleeding after tooth extraction.

Abstract Background Neuroblastoma (NB) is a common extracranial malignancy with high mortality in children. Recently, super-enhancers (SEs) have been reported to play a critical role in the tumorigenesis and development of NB via regulating a wide range of oncogenes Thus, the synthesis and identification of chemical inhibitors specifically targeting SEs are of great urgency for the clinical therapy of NB. This study aimed to characterize the activity of the SEs inhibitor GNE987, which targets BRD4, in NB. Results In this study, we found that nanomolar concentrations of GNE987 markedly diminished NB cell proliferation and survival via degrading BRD4. Meanwhile, GNE987 significantly induced NB cell apoptosis and cell cycle arrest. Consistent with in vitro results, GNE987 administration (0.25 mg/kg) markedly decreased the tumor size in the xenograft model, with less toxicity, and induced similar BRD4 protein degradation to that observed in vitro. Mechanically, GNE987 led to significant downregulation of hallmark genes associated with MYC and the global disruption of the SEs landscape in NB cells. Moreover, a novel candidate oncogenic transcript, FAM163A, was identified through analysis of the RNA-seq and ChIP-seq data. FAM163A is abnormally transcribed by SEs, playing an important role in NB occurrence and development. Conclusion GNE987 destroyed the abnormal transcriptional regulation of oncogenes in NB by downregulating BRD4, which could be a potential therapeutic candidate for NB.

ObjectiveChordoma is a slow-growing and locally aggressive cancer, which arises from the remnants of the primitive notochord. The first line treatment for the skull base chordoma is neurosurgery. Gamma Knife radiosurgery (GKS) is often be chosen especially in the setting of residual or recurrent chordomas. The purpose of this study is to evaluate the prognosis of patients with skull base chordoma who underwent GKS.MethodsThe present study was a retrospective analysis of 53 patients with skull base chordomas who underwent GKS. Univariate Cox and Kaplan-Meier survival analysis were performed to analyze the relationship between the tumor control time and the clinical characteristics.ResultsThe 1-, 2-, 3-, and 5-year progression free survival (PFS) rates were 87, 71, 51, and 18%, respectively. After performing the univariate analysis, the clinical characteristics were not found to be significantly associated with the time of PFS; however, surgical history, peripheral dose, and tumor volume did have tendencies to predict the prognosis.ConclusionGKS provided a safe and relatively effective treatment for residual or recurrent chordomas after surgical resection. A higher tumor control rate depends on two approaches, an appropriate dose of radiation for the tumor and the accurate identification of the tumor margins.

Background. Arising from T progenitor cells, T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignant tumor, accounting for 15% of childhood ALL and 25% of adult ALL. Composing of putative enhancers in close genomic proximity, super enhancer (SE) is critical for cell identity and the pathogenesis of multiple cancers. Belonging to the cytosolute linker protein group, FYB1 is essential for TCR signaling and extensively studied in terms of tumor pathogenesis and metastasis. Dissecting the role of FYN binding protein 1 (FYB1) in T-ALL holds the potential to improve the treatment outcome and prognosis of T-ALL. Methods. In this study, SEs were explored using public H3K27ac ChIP-seq data derived from T-ALL cell lines, AML cell lines and hematopoietic stem and progenitor cells (HSPCs). Downstream target of FYB1 gene was identified by RNA-seq. Effects of shRNA-mediated downregulation of FYB1 and immunoglobulin lambda-like polypeptide 1 (IGLL1) on self-renewal of T-ALL cells were evaluated in vitro and/or in vivo. Results. As an SE-driven gene, overexpression of FYB1 was observed in T-ALL, according to the Cancer Cell Line Encyclopedia database. In vitro, knocking down FYB1 led to comprised growth and enhanced apoptosis of T-ALL cells. In vivo, downregulation of FYB1 significantly decreased the disease burden by suppressing tumor growth and improved survival rate. Knocking down FYB1 resulted in significantly decreased expression of IGLL1 that was also an SE-driven gene in T-ALL. As a downstream target of FYB1, IGLL1 exerted similar role as FYB1 in inhibiting growth of T-ALL cells. Conclusion. Our results suggested that FYB1 gene played important role in regulating self-renewal of T-ALL cells by activating IGLL1, representing a promising therapeutic target for T-ALL patients.

PurposeTo evaluate the influence of GATA3 rs3824662 on pre-B-cell acute lymphoblastic leukemia (pre-B-cell ALL) susceptibility and long-term prognosis in Han Chinese children with pre-B-cell ALL treated with the CCLG-2008 protocol at the Children’s Hospital of Soochow University.MethodsA total of 256 patients with childhood pre-B-cell ALL under the CCLG-2008 protocol were enrolled in this study, and 174 healthy children were used as case controls. GATA3 rs3824662 genotyping was performed using a polymerase chain reaction, followed by Sanger sequencing. The association of genotype with clinical characteristics, treatment response, adverse events, and outcomes were analyzed.ResultsThe A allele frequency of GATA3 rs3824662 in patients with pre-B cell ALL was significantly higher than that in healthy children (OR = 1.41, 95% CI = 1.042–1.908; P = 0.026). Among patients with pre-B-cell ALL, the GATA3 rs3824662 AA genotype was associated with poor prednisolone response and high blast cell burden on day 15 of the induction therapy (P = 0.011 and 0.007, respectively). Patients with the rs3824662 AA variant suffered more episodes of sepsis than those with the CC or CA variants (P = 0.021). The GATA3 rs3824662 AA genotype was significantly associated with sepsis [hazard ratio (HR) = 3.375; P = 0.01]. No significant differences were found in the cumulative incidence of relapse, overall survival, and event-free survival among all genotypes.ConclusionGATA3 rs3824662 was associated with susceptibility in Han Chinese children with pre-B-cell ALL and could be a possible risk factor for poor early treatment response and treatment-related sepsis.

Purpose/ObjectiveThis study aimed to evaluate the nutritional status of children subjected to allogeneic hematopoietic stem cell transplantation (alloHSCT) in the first 100 days. Objectives were to clarify the effect of weight loss on clinical outcomes, and to analyze factors influencing weight loss.MethodsEighty pediatric patients receiving alloHSCT were enrolled in the study. Body mass index (BMI) z-scores and weight for age (WFA) z-scores were collected. A multivariate regression model was set up to investigate factors affecting weight loss. Post-transplant clinical outcomes relative to weight loss on 100 days after transplantation were analyzed.ResultsAt admission, eight patients (10%) were underweight, the number had increased to 23 (30.67%) by 100 days post-HSCT. On day + 100, only nutrition screening tool for childhood cancer (SCAN) scores ≥ 3 (OR: 4.474, 95% CI: 1.215, 16.472; P = 0.024) and acute graft versus host disease (aGVHD) (OR: 9.915, 95% CI: 3.302, 29.771; P < 0.001) were regarded as significant influencing factors of weight loss. The Weight loss ≥ 5% group was associated with longer hospital stays (P = 0.001), greater cost of inpatient treatment (P = 0.001), and a higher incidence of 100-day re-admission and intensive care unit (ICU) transfer (P = 0.03 and P = 0.033, respectively). Cumulative number of fever days (P = 0.023) and antibiotic use (P = 0.007) also increased significantly. The Weight loss ≥ 5% group had a significantly lower one-year overall survival rate compared with the Weight loss < 5% group (P = 0.015).ConclusionPediatric patients’ nutritional status declined significantly after HSCT. Weight loss within the first 100 days influenced short-term clinical outcomes and one-year overall survival.

Abstract Recent studies reported that Methyl-CpG–binding domain protein 2 (MBD2) promoted M2 macrophages accumulation to increase bleomycin-induced pulmonary fibrosis. However, the role and mechanism of action of MBD2 in macrophages differentiation and renal fibrosis remain largely unknown. In the current study, MBD2 not only promoted the differentiation of resting M0 macrophages to polarized M2 macrophages, but also induced them to polarized M1 macrophages and the transition of M2 to M1 macrophages. ChIP analysis demonstrated that MBD2 physically interacted with the promoter region of the CpG islands of G0S2 genes, and then activated their expression by inducing hypomethylation of the promoter region. Interestingly, the data demonstrated that the role of G0S2 in macrophages differentiation is consistent with MBD2. Furthermore, Co-culture of activated M1 macrophages and murine embryonic NIH 3T3 fibroblasts indicated that MBD2 mediated the M1-induction of ECM production by embryonic NIH 3T3 fibroblasts via promotion of G0S2. In addition, we also found that inhibition of MBD2 suppressed LPS induced the expression of p53 as well as activation and expression of stat3 in RAW264.7 macrophages. In vivo, MBD2 LysMcre attenuated unilateral ureteral obstruction (UUO) and ischemia/reperfusion (I/R)-induced renal fibrosis via downregulation of G0S2, which was demonstrated by the downregulation of fibronectin (FN), collagen I and IV, α-SMA, G0S2. These data collectively demonstrated that MBD2 in macrophages contributed to UUO and I/R-induced renal fibrosis through the upregulation of G0S2, which could be a target for treatment for chronic kidney disease.

Abstract Recent studies uncovered the emerging roles of SAPCD2 (suppressor anaphase-promoting complex domain containing 2) in several types of human cancer. However, the functions and underlying mechanisms of SAPCD2 in the progression of neuroblastoma (NB) remain elusive. Herein, through integrative analysis of public datasets and regulatory network of GSK-J4, a small-molecule drug with anti-NB activity, we identified SAPCD2 as an appealing target with a high connection to poor prognosis in NB. SAPCD2 promoted NB progression in vitro and in vivo. Mechanistically, SAPCD2 could directly bind to cytoplasmic E2F7 but not E2F1, alter the subcellular distribution of E2F7 and regulate E2F activity. Among the E2F family members, the roles of E2F7 in NB are poorly understood. We found that an increasing level of nuclear E2F7 was induced by SAPCD2 knockdown, thereby affecting the expression of genes involved in the cell cycle and chromosome instability. In addition, Selinexor (KTP-330), a clinically available inhibitor of exportin 1 (XPO1), could induce nuclear accumulation of E2F7 and suppress the growth of NB. Overall, our studies suggested a previously unrecognized role of SAPCD2 in the E2F signaling pathway and a potential therapeutic approach for NB, as well as clues for understanding the differences in subcellular distribution of E2F1 and E2F7 during their nucleocytoplasmic shuttling.

Abstract Background The present study aimed to report a technically improved operation on the surgical exposure of labially impacted maxillary canine, elaborating the management of soft tissue to achieve better aesthetic results, and post-treatment periodontal health. Methods Patients sought orthodontic treatment with unilateral labially impacted maxillary canines were selected in this study. The impacted teeth were assigned to the experimental group and contralateral unimpacted canines were assigned to the control group. The impacted canines were surgically exposed with dissected dental follicle (DF) stitching to muscle and mucosa surrounding the crowns. The gingival index (GI), probing depth (PD), the width of the keratinized gingiva (WKG), gingival scars (GS), bone loss (BL), and apical root resorption (ARR) were recorded after the removal of the fixed appliance. A two-sample t-test was used for independent samples for parametric variables. Results A total of 24 patients with unilateral maxillary canine impaction were successfully treated. The outcomes of GI, WKG, GS, BL, and ARR did not indicate statistical significance between the experimental group and the control group. Conclusions The preservation of DF promotes soft tissue management in combined surgical and orthodontic treatment of labially impacted maxillary canine to achieve better periodontal status. Trial Registration Chinese Clinical Trial Registry ChiCTR2000029091, 2020-01-12.

Abstract Background Acute myeloid leukemia (AML) is a myeloid neoplasm accounts for 7.6% of hematopoietic malignancies. AML is a complex disease, and understanding its pathophysiology is contributing to the improvement in the treatment and prognosis of AML. In this study, we assessed the expression profile and molecular functions of CCAAT enhancer binding protein gamma (CEBPG), a gene implicated in myeloid differentiation and AML progression. Methods shRNA mediated gene interference was used to down-regulate the expression of CEBPG in AML cell lines, and knockdown efficiency was detected by RT-qPCR and western blotting. The effect of knockdown on the growth of AML cell lines was evaluated by CCK-8. Western blotting was used to detect PARP cleavage, and flow cytometry were used to determine the effect of knockdown on apoptosis of AML cells. Genes and pathways affected by knockdown of CEBPG were identified by gene expression analysis using RNA-seq. One of the genes affected by knockdown of CEBPG was Eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1), a known repressor of translation. Knockdown of EIF4EBP1 was used to assess its potential role in AML progression downstream of CEBPG. Results We explored the ChIP-Seq data of AML cell lines and non-AML hematopoietic cells, and found CEBPG was activated through its distal enhancer in AML cell lines. Using the public transcriptomic dataset, the Cancer Cell Line Encyclopedia (CCLE) and western blotting, we also found CEBPG was overexpressed in AML. Moreover, we observed that CEBPG promotes AML cell proliferation by activating EIF4EBP1, thus contributing to the progression of AML. These findings indicate that CEBPG could act as a potential therapeutic target for AML patients. Conclusion In summary, we systematically explored the molecular characteristics of CEBPG in AML and identified CEBPG as a potential therapeutic target for AML patients. Our findings provide novel insights into the pathophysiology of AML and indicate a key role for CEBPG in promoting AML progression.

Local anesthesia (LA) is the most important pain management process in oral and maxillofacial surgery. Safe and effective LA not only enable patients to obtain high-quality treatment, but also relieve the anxiety of patients when they come to the clinic. The choices of local anesthetic and injection methods determine the success of LA to a great extent. At present, in most countries or regions, common local anesthetics used in oral and maxillofacial surgery belong to amides and they are injected into patients' body mainly through block or infiltration anesthesia. In addition, the operators' technique level, patient's subjective psychology and anatomical variation of maxillofacial structure also have a strong influence on LA in dental clinic. Due to the existence of above factors, the worldwide success rates of LA in oral and maxillofacial surgery is very different. There are no specific LA methods that ensure 100% successful LA rates. Fortunately, the development of new local anesthetic and injection technology are providing us with new ideas to solve this problem. This review mainly report the new research progress on LA in oral and maxillofacial surgery in recent decades and help clinicians with dental LA operation.

Abstract Background While great attention has been paid to motor and cognitive impairments in children with neonatal Hypoxic-Ischemic Encephalopathy (HIE), sleep related circadian rhythm problems, although commonly present, are often neglected. Subsequently, no early clinical indicators have been reported to correlate with sleep-related circadian dysfunction during development. Methods In this study, we first analyzed patterns of the amplitude integrated electroencephalogram (aEEG) in a cohort of newborns with various degrees of HIE. Next, during follow-ups, we collected information of sleep and circadian related problems in these patients and performed correlation analysis between aEEG parameters and different sleep/circadian disorders. Results A total of 101 neonates were included. Our results demonstrated that abnormal aEEG background pattern is significantly correlated with circadian rhythmic (r = 0.289, P = 0.01) and breathing issues during sleep (r = 0.237, P = 0.037). In contrast, the establishment of sleep–wake cycle (SWC) showed no correlation with sleep/circadian problems. Detailed analysis showed that summation of aEEG score, along with low base voltage (r = 0.272, P = 0.017 and r = -0.228, P = 0.048, respectively), correlates with sleep circadian problems. In contrast, background pattern (BP) score highly correlates with sleep breathing problem (r = 0.319, P = 0.004). Conclusion Abnormal neonatal aEEG pattern is correlated with circadian related sleep problems. Our study thus provides novel insights into predictive values of aEEG in sleep-related circadian problems in children with HIE.

Abstract Green hydrogen represents a critical underpinning technology for achieving carbon neutrality. Although researchers often fixate on its energy inputs, a truly ‘green’ hydrogen production process would also be sustainable in terms of water and materials inputs. To address this holistic challenge, we demonstrate a new green hydrogen production system which can utilize secondary wastewater as the input (preserving scarce fresh water supplies for drinking and sanitation). The enabling feature of the proposed system is a self‐grown bifunctional CoNi electrode which consists of ultrathin, spontaneously deposited CoNi nanosheets on a three‐dimensional nickel foam. As such, a green synthesis process was developed using an immersion procedure at room‐temperature with zero net energy input. Testing revealed that the synthesized CoNi electrodes can reach a current density of 10 mA cm−2 at a small overpotential of 197 mV for the hydrogen evolution reaction and 315 mV for the oxygen evolution reaction in alkalified wastewater. The values are ~16.5% and ~6.5% smaller than that from precious catalysts (20 wt% Pt/C and RuO2, respectively). Importantly, this CoNi catalyst offers outstanding durability for overall wastewater splitting. A prototype solar‐energy‐powered rooftop wastewater splitting system was constructed and can produce more than 100 L hydrogen on a sunny day in Sydney, Australia. Taken together, these results indicate that it is promising to unlock holistically green routes for hydrogen production by wastewater uplifting with regards to water, energy, and materials synthesis.

Due to the lack of blood vessels, nerves and lymphatic vessels, the capacity of articular cartilage to heal is extremely limited. Once damaged, it is urgent for articular cartilage to repair the injury. In recent years, there has been an increase in cartilage tissue engineering studies. Self-assembling peptide hydrogel as a kind of hydrogels composed of peptides and water is widely used in cartilage tissue engineering. Under noncovalent interactions such as electrostatic interaction, hydrophobic interaction, hydrogen bonding and pi-pi stacking force, peptides self-assemble into three-dimensional (3D) structures that mimic the natural extracellular matrix and allow cells to grow, proliferate and differentiate. Because SAPHs have excellent biocompatibility and biodegradability, variable mechanical properties, low immunogenicity, injectability, and the ability to load cells and bioactive substances, many researchers utilized them to promote the repair and regeneration of articular cartilage after damage. Therefore, the purpose of this review is to sum up the composition, injury characteristics, and treatments of articular cartilage, as well as the action of SAPHs in repairing articular cartilage damage.

Autophagy has dual roles in cancer, resulting in cellular adaptation to promote either cell survival or cell death. Modulating autophagy can enhance the cytotoxicity of many chemotherapeutic and targeted drugs and is increasingly considered to be a promising cancer treatment approach. Cynaropicrin (CYN) is a natural compound that was isolated from an edible plant (artichoke). Previous studies have shown that CYN exhibits antitumor effects in several cancer cell lines. However, it anticancer effects against neuroblastoma (NB) and the underlying mechanisms have not yet been investigated. More specifically, the regulation of autophagy in NB cells by CYN has never been reported before. In this study, we demonstrated that CYN induced apoptosis and protective autophagy. Further mechanistic studies suggested that ER stress-induced autophagy inhibited apoptosis by activating the p62/Keap1/Nrf2 pathways. Finally, in vivo data showed that CYN inhibited tumour growth in xenografted nude mice. Overall, our findings suggested that CYN may be a promising candidate for the treatment of NB, and the combination of pharmacological inhibitors of autophagy may hold novel therapeutic potential for the treatment of NB. Our paper will contribute to the rational utility and pharmacological studies of CYN in future anticancer research.

Recently, core enterprises are compelled to invest in the environmental responsibility of upstream suppliers, since their brand image and market share will be significantly impacted when suppliers fail to comply with environmental regulations. However, the effectiveness of the core enterprises’ investment efficiency is limited by insufficient environmental knowledge. Although cooperating with the knowledge-advantaged environmental non-governmental organization (ENGO) may be an effective solution, we observe from the recent examples that not all core enterprises are willing to cooperate in a competitive market. Within this context, we develop a theoretical model to investigate whether competitive core enterprises can benefit from cooperating with the knowledge-advantaged ENGO to motivate the supplier’s environmental responsibility. Our results show that cooperation incentivizes core enterprises’ investments in the supplier’s environmental responsibility, which in turn motivates better environmental responsibility of the supplier. However, we illustrate that cooperation is not necessarily the optimal strategy for core enterprises in the duopoly scenario. Specifically, as the knowledge absorption ability increases, a core enterprise may free-ride on another’s investment, shifting its strategic preference from cooperating to not cooperating. In addition, competition may stimulate the core enterprises’ investments and cooperation motivation, thus improving the total environmental effort and supply chain members’ profits. Our findings provide insights into the competitive core enterprises’ strategic choice regarding suppliers’ environmental responsibility management.

AIM:To observe the near stereoscopic visual function of adolescents with different degrees of myopic anisometropia after being corrected by spectacles and orthokeratology.METHODS:In this prospective clinical research,220 patients aged 10-20 years old with myopic anisometropia were recruited between March 2017 and December 2018. All the patients were divided into four groups according to the difference of cycloplegic spherical equivalent refractive(SER)error between the two eyes: group of 76 cases without anisometropia(SER error difference less than 1.00D), group of 60 cases with mild anisometropia(SER error difference of 1.00-

BackgroundAged people are maintaining many natural teeth due to improved oral health. However, compromised general health and poor oral hygiene habits at earlier ages resulted in poor status of preserved teeth. Therefore, tooth extraction is required in many aged people. More knowledge is needed because there are many risk factors during the surgery in frail aged adults. The aim of this study was to evaluate the cardiovascular response of such a population during tooth extraction and analyze risk factors to provide clinical guidance.MethodsA retrospective study was performed on aged patients with systemic diseases who underwent tooth extraction. Data regarding demographic profiles and cardiovascular parameters of heart rate and blood pressure were collected preoperative, when local anesthesia was administered, at the beginning of tooth extraction, 5 min after tooth extraction, and postoperative. The effects of risk factors, including age, sex, and systemic diseases on these parameters were analyzed with a multilevel model.ResultsHeart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) of aged patients increased significantly when performing local anesthesia and tooth extraction. During the operation, the older patients (β = 2.011, P = 0.005) and the diabetics (β = 3.902, P < 0.0001) were associated with higher SBP, while those with more tooth extractions exhibited higher HR (β = 0.893, P = 0.007). Women patients showed both significantly elevated HR (β = 1.687, P < 0.0001) and SBP (β = 2.268, P < 0.0001). However, for coronary artery disease patients, HR (β = −2.747, P < 0.0001) and blood pressure [SBP (β = −4.094, P < 0.0001) and DBP (β = −0.87, P = 0.016)] were markedly lower than those of patients without a diagnosis of coronary artery disease.ConclusionCardiovascular response of aged outpatients with systemic diseases during tooth extraction is quite significant. Age, sex, systemic diseases, and the number of tooth extraction could be risk factors closely associated with cardiovascular response. The findings might provide safety guidance for dentists on tooth extraction in this population.

Reluctance machines with DC field coil in stator are a competitive candidate for starter generation application, due to the elimination of rare-earth permanent magnet (PM), robust structures, and controllable excitation. However, due to the poor excitation ability of DC field coils, the torque density is disadvantageous. Moreover, with the increase in the DC field current, it is exposed to the risk of extra DC saturation in stator teeth. As a consequence, the torque density and efficiency are both constrained. To solve the aforementioned problems, based on the comprehensive consideration of production cost and torque performance, this study proposed a novel type of hybrid reluctance machine with dual-ferrite–assisted in stator slots. The inner-layer ferrite PM is magnetized tangentially, which can effectively achieve the DC-saturation–relieving effect, while the outer-layer ferrite PM is magnetized radially to increase the machine torque density through the flux modulation effect. Based on finite element analysis, the machine torque density and efficiency can be improved by 20 and 5%, respectively. Furthermore, to simplify the excitation system of the DC terminal, a two-stage excitation method is proposed by splitting some turns of armature winding to feed DC field winding with passive rectifier. No power switching devices are needed for the excitation system in this way, making the system highly robust. The effectiveness of the proposed design is verified by time-stepping finite element analysis.

Acute myeloid leukemia (AML) represents an aggressive hematopoietic malignancy with a prognosis inferior to that of other leukemias. Recent targeted therapies offer new opportunities to achieve better treatment outcomes. However, due to the complex heterogeneity of AML, its prognosis remains dismal. In this study, we first identified the correlation between high expression of BRD4 and overall survival of patients with AML. Targeted degradation of BRD2, BRD3, and BRD4 proteins by dBET1, a proteolysis-targeting chimera (PROTAC) against the bromodomain and extra-terminal domain (BET) family members, showed cytotoxic effects on Kasumi (AML1-ETO), NB4 (PML-RARa), THP-1 (MLL-AF9), and MV4-11 (MLL-AF4) AML cell lines representing different molecular subtypes of AML. Furthermore, we determined that dBET1 treatment arrested cell cycling and enhanced apoptosis and c-MYC was identified as the downstream target. Collectively, our results indicated that dBET1 had broad anti-cancer effects on AML cell lines with different molecular lesions and provided more benefits to patients with AML.

PurposeThe computed tomography fat attenuation index (FAI) is an ideal quantifiable imaging factor to identify the inflammation degree of peri-tumor adipose tissue. We aimed to verify whether FAI could reflect peri-tumor adipose inflammation, predict the survival outcome of renal cell carcinoma (RCC), and discover transcriptomic features of tumor tissues and adjacent adipocytes.Materials and MethodsTwo clinical cohorts (Fudan University Shanghai Cancer Center [FUSCC] cohort [n=129] and TCGA cohort [n=218]) were used to explore the association between FAI and clinical outcome. A prospective cohort (n = 19) was used to discover the molecular phenotyping of peri-tumor adipose tissue and tumor tissue according to their FAI value. A clinical cohort (n = 32) in which patients received cyto-reductive surgery was used to reveal the dynamic change of FAI.ResultsA high peri-tumor FAI was significantly associated with a worse outcome in both the FUSCC (HR = 2.28, p = 0.01) and the TCGA cohort (HR = 2.24, p

The objective of this study is to prepare CNT/AlSi10Mg composites using mechanical ball milling combined with SPS. The study investigates the influence of ball-milling time and CNT content on the mechanical and corrosion resistance of the composite. This is performed to address the challenge of CNTs dispersion and to understand how CNTs impact the mechanical and corrosion resistance of the composites. The morphology of the composites was characterized using scanning electron microscopy (SEM) transmission electron microscopy (TEM) and Raman spectroscopy, and the mechanics and corrosion resistance of the composite materials were tested. The results demonstrate that the uniform dispersion of CNTs can significantly enhance both the mechanical properties and corrosion resistance of the material. Specifically, when the ball-milling time was 8 h, CNTs were uniformly dispersed in the Al matrix. The CNT/AlSi10Mg composite shows the best interfacial bonding when the mass fraction of CNTs is 0.8 wt.%, with a tensile strength of −256 MPa. This is 69% higher than the original matrix material without the addition of CNTs. Moreover, the composite exhibited the best corrosion resistance.

Because of their beautiful appearance, strong crossing ability, and reasonable stress performance, the application of tied steel box arch bridges is becoming more and more extensive. Bridge construction monitoring can control and adjust the deviation state to ensure the stress and linear state of the bridge after completion. This study carried out a symmetrical construction monitoring analysis and completed state evaluation of the newly built Dafeng River Bridge in Guangxi Province based on the finite element method. MIDAS Civil finite element software is used for simulation analysis to calculate the deformation and stress of the tied steel box arch bridge at the construction and completion stages. The tensile and compressive stress of the main arch and transverse brace, as well as the cumulative displacements of the main arch and lattice beam, are symmetrically distributed. The maximum tensile and compressive stresses are 15.1 MPa and 74.6 MPa, respectively, less than the specification’s allowable value. Meanwhile, for the completed bridge under the loading combinations of serviceability limit state and bearing capacity ultimate limit state, the stress of the main arch, transverse brace, and lattice beam meets the specification requirements. The maximum cable forces of the suspender and tie rod under the bearing capacity ultimate limit state are 2189.4 kN and 2991.2 kN, and their corresponding minimum safety factors are 3.2 and 2.7. In addition, the deviations between the on-site monitoring and the finite element theoretical values are within the specification allowable range for the cable force of the suspender and tie rod and the bridge deck alignment. It indicates that the bridge construction monitoring effect is reasonable and ideal, and the symmetrically finite element simulation analysis can provide a theoretical basis for construction monitoring.

Recovery of valuable metals from red mud smelting separation slag is important for environmental protection and saving of natural resources. In this paper, we propose a recycling process of red mud smelting separation slag by mineral phase reconstruction conducted under an air atmosphere. In this process, NaOH and Ca(OH)2 roasting of Al2O3 and NaAlSiO4 was performed, and Al2O3 and SiO2 were converted into alkaline-soluble NaAlO2 and Ca2SiO4, respectively. In the consequent steps, more than 80% of Al2O3 was selectively dissolved into a leaching solution using a NaOH solution under 95 °C, and the obtained NaAlO2 solution can be used as a source for extracting alumina. Then, a 20 wt.% HCl solution was used to remove SiO2 from the residue, obtaining a SiO2-containing solution and a concentrated residue of undissolved TiO2 and CaO. Finally, this mineral phase reconstruction process can enable a higher metal leaching rate, and this study provides a novel, clean, and sustainable method for recycling valuable metals from red mud smelting separation slag.

Iron ores always contain several forms of alumina, which may have different effect on sintering performance. In this paper, sinter pot tests were systematically conducted with various alumina types and contents by means of alumina additives substituting for the corresponding types of alumina, and the relevant action mechanism on sintering performance was clarified by the mineralogy of product sinter. The results show that kaolinite is beneficial to the granulation process rather than other three alumina types. In addition, it contributes to relatively better sintering performance while aluminous goethite ranks the only next, followed by gibbsite and free alumina. Mechanism analysis indicates that kaolinite and aluminous goethite are preferable to achieve relatively lower sinter porosity and higher amount of silico-ferrite of calcium and alumina (SFCA) compared with gibbsite and free alumina. Besides, the former two alumina types are apt to promote the formation of higher strength SFCA such as dendritic and acicular SFCA. Furthermore, much tighter interlocking texture in product sinter is formed as alumina occurs in kaolinite or aluminous goethite. Kaolinite and aluminous goethite are the preferably desirable alumina types for sintering rather than free alumina and gibbsite.

This study is aimed to obtain better-quality Ni–Cr composite sinter for the production of 300 series stainless steel via the sintering-blast furnace process at lower cost. Based on the complementary advantages of limonitic nickel laterite and chromite, co-sintering pot tests of the two ores were conducted in various chromite proportions and then strengthened by multi-force fields. Mechanistic analysis was performed, including the chemistry and mineralogy of product sinter and the thermodynamic and kinetic conditions of the co-sintering process. The results indicate that the addition of chromite effectively improves tumble index and productivity, especially at a chromite ratio of 15%, due to the improvement of sinter microstructure and the thermodynamic and kinetic conditions during sintering. However, solid fuel rate is increased gradually because of the greater amount of high smelting minerals. With the application of multi-force fields, higher tumble index is obtained owing to the further densification of sinter bed and the formation of tighter interlocking texture. Solid fuel rate is greatly decreased due to the efficient supply of extra physical heat. Productivity is weakened to some extent as the flame fronts speed is reduced. In addition, excellent metallurgical performance is achieved. The co-sintering process of limonitic nickel laterite and chromite is significantly improved via multi-force fields.

Abstract Background Trichomes are excellent model systems for the analysis of cell differentiation and play essential roles in plant protection. From cucumber inbred line ‘WD1’, we identified an EMS-induced trichome abnormally developing mutant, nps, which exhibited smaller, denser and no pyramid-shaped head trichomes. Results Using F2 and BC1 populations constructed from a cross between nps and ‘9930’, the genetic analysis showed that the nps trait is controlled by a single recessive nuclear gene. We identified CsNps by map-based cloning with 576 individuals of the F2 population generated from the cross of nps and inbred line ‘9930’. The CsNps was located at a 13.4-kb genomic region on chromosome 3, which region contains three predicted genes. Sequence analysis showed that only one single nucleotide mutation (C → T) between 9930 and nps was found in the second exon of Csa3G748220, a plant-specific class I HD-Zip gene. The result of allelism test also indicated that nps is a novel allelic mutant of Mict (Micro-trichome). Thus, nps was renamed mict-L130F. By comparing the transcriptome of mict-L130F vs WD1 and 06–2 (mict) vs 06–1 (wildtype, near-isogenic line of 06–2), several potential target genes that may be related to trichome development were identified. Conclusions Our results demonstrate that Mict-L130F is involved in the morphogenesis of trichomes. Map-based cloning of the Mict-L130F gene could promote the study of trichome development in cucumber.

Abstract Background T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease with a high risk of induction failure and poor outcomes, with relapse due to drug resistance. Recent studies show that bromodomains and extra-terminal (BET) protein inhibitors are promising anti-cancer agents. ARV-825, comprising a BET inhibitor conjugated with cereblon ligand, was recently developed to attenuate the growth of multiple tumors in vitro and in vivo. However, the functional and molecular mechanisms of ARV-825 in T-ALL remain unclear. This study aimed to investigate the therapeutic efficacy and potential mechanism of ARV-825 in T-ALL. Methods Expression of the BRD4 were determined in pediatric T-ALL samples and differential gene expression after ARV-825 treatment was explored by RNA-seq and quantitative reverse transcription-polymerase chain reaction. T-ALL cell viability was measured by CCK8 assay after ARV-825 administration. Cell cycle was analyzed by propidium iodide (PI) staining and apoptosis was assessed by Annexin V/PI staining. BRD4, BRD3 and BRD2 proteins were detected by western blot in cells treated with ARV-825. The effect of ARV-825 on T-ALL cells was analyzed in vivo. The functional and molecular pathways involved in ARV-825 treatment of T-ALL were verified by western blot and chromatin immunoprecipitation (ChIP). Results BRD4 expression was higher in pediatric T-ALL samples compared with T-cells from healthy donors. High BRD4 expression indicated a poor outcome. ARV-825 suppressed cell proliferation in vitro by arresting the cell cycle and inducing apoptosis, with elevated poly-ADP ribose polymerase and cleaved caspase 3. BRD4, BRD3, and BRD2 were degraded in line with reduced cereblon expression in T-ALL cells. ARV-825 had a lower IC50 in T-ALL cells compared with JQ1, dBET1 and OTX015. ARV-825 perturbed the H3K27Ac-Myc pathway and reduced c-Myc protein levels in T-ALL cells according to RNA-seq and ChIP. In the T-ALL xenograft model, ARV-825 significantly reduced tumor growth and led to the dysregulation of Ki67 and cleaved caspase 3. Moreover, ARV-825 inhibited cell proliferation by depleting BET and c-Myc proteins in vitro and in vivo. Conclusions BRD4 indicates a poor prognosis in T-ALL. The BRD4 degrader ARV-825 can effectively suppress the proliferation and promote apoptosis of T-ALL cells via BET protein depletion and c-Myc inhibition, thus providing a new strategy for the treatment of T-ALL.

Our previous study demonstrated that the methyl-CpG-binding domain protein 2 (MBD2) mediates vancomycin (VAN)-induced acute kidney injury (AKI). However, the role and regulation of MBD2 in septic AKI are unknown. Herein, MBD2 was induced by lipopolysaccharide (LPS) in Boston University mouse proximal tubules (BUMPTs) and mice. For both in vitro and in vivo experiments, we showed that inhibition of MBD2 by MBD2 small interfering RNA (siRNA) and MBD2-knockout (KO) substantially improved the survival rate and attenuated both LPS and cecal ligation and puncture (CLP)-induced AKI, renal cell apoptosis, and inflammatory factor production. Global genetic expression analyses and in vitro experiments suggest that the expression of protein kinase C eta (PKCη), caused by LPS, is markedly suppressed in MBD2-KO mice and MBD2 siRNA, respectively. Mechanistically, chromatin immunoprecipitation (ChIP) analysis indicates that MBD2 directly binds to promoter region CpG islands of PKCη via suppression of promoter methylation. Furthermore, PKCη siRNA improves the survival rate and attenuates LPS-induced BUMPT cell apoptosis and inflammatory factor production via inactivation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK)1/2, which were further verified by PKCη siRNA treatment in CLP-induced AKI. Finally, MBD2-KO mice exhibited CLP-induced renal cell apoptosis and inflammatory factor production by inactivation of PKCη/p38MAPK and ERK1/2 signaling. Taken together, the data indicate that MBD2 mediates septic-induced AKI through the activation of PKCη/p38MAPK and the ERK1/2 axis. MBD2 represents a potential target for treatment of septic AKI.

ObjectiveThis study aims to detect the invisible metabolic abnormality in PET images of patients with anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis using a multivariate cross-classification method.MethodsParticipants were divided into two groups, namely, the training cohort and the testing cohort. The training cohort included 17 healthy participants and 17 patients with anti-LGI1 encephalitis whose metabolic abnormality was able to be visibly detected in both the medial temporal lobe and the basal ganglia in their PET images [completely detectable (CD) patients]. The testing cohort included another 16 healthy participants and 16 patients with anti-LGI1 encephalitis whose metabolic abnormality was not able to be visibly detected in the medial temporal lobe and the basal ganglia in their PET images [non-completely detectable (non-CD) patients]. Independent component analysis (ICA) was used to extract features and reduce dimensions. A logistic regression model was constructed to identify the non-CD patients.ResultsFor the testing cohort, the accuracy of classification was 90.63% with 13 out of 16 non-CD patients identified and all healthy participants distinguished from non-CD patients. The patterns of PET signal changes resulting from metabolic abnormalities related to anti-LGI1 encephalitis were similar for CD patients and non-CD patients.ConclusionThis study demonstrated that multivariate cross-classification combined with ICA could improve, to some degree, the detection of invisible abnormal metabolism in the PET images of patients with anti-LGI1 encephalitis. More importantly, the invisible metabolic abnormality in the PET images of non-CD patients showed patterns that were similar to those seen in CD patients.

BackgroundChina is a country with a high burden of tuberculosis (TB), and students are the high-risk group for TB. The enrollment scale of colleges has increased dramatically due to the advancement of the enrollment expansion system of Chinese colleges. Consequently, this has brought severe challenges to TB prevention and control in colleges. In 2017, a new TB control guide for schools was issued in China, which included the 8 core knowledge of TB. The target of the overall awareness rate on TB among population was “≥85%,” which was proposed by the “13th Five-Year” National TB Control Plan in China. The cognition of the 8 core knowledge of TB in the new guide among college students is crucial to achieve this target, but few studies on this have been reported. Based on the abovementioned new situation and the new guide, this study aimed to investigate and analyze the cognition, attitudes, and health education needs on TB among freshmen of a medical college in Guangxi province, and discuss how to optimize TB health education in colleges in China.MethodsA cross-sectional study was conducted among freshmen of a medical college in Guangxi, China. A self-designed questionnaire was used to conduct an on-site questionnaire survey. The data was entered in Epidata 4.4.2.1 and was analyzed using SPSS version 25.0. Including descriptive statistics and t-test, and the criterion for statistically significant difference was p < 0.05.ResultsA total of 583 freshmen responded to the survey questionnaires. Regarding cognition about the 5 related knowledge of TB, 551 (94.5%) freshmen knew about the predilection site of TB, while 333 (57.1%), 328 (56.4%), 257 (44.1%), and 201 (34.5%) freshmen knew about the pathogen, the policies about free treatment, the designated hospitals, and the World TB Day, respectively. Regarding cognition on the 8 core knowledge of TB, the overall awareness rate among the freshmen is 73.3%(3,420/4,664); the awareness rate of the knowledge that “guarantee adequate sleep, reasonable diet, and strengthen physical exercise can reduce the incidence of TB” among them was the highest at 88.7% (517/583); and the awareness rate of the knowledge that “coughing or sputum expectoration occurred for more than 2 weeks should be suspected of infecting TB and seeking medical treatment in time” among them was the lowest at 47.5% (277/583). Whether students received health education on TB (T = 4.267, p = 0.000) and whether students heard of TB (T = 3.739, p = 0.000) are the main factors of cognition. Five hundred sixty-two (96.4%) and 565 (96.9%) freshmen were willing to learn and tell others about the knowledge of TB, respectively. Three hundred seventy (63.5%.) freshmen, the highest amount, were willing to accept TB health education in the forms of “website, Weibo, and WeChat.”ConclusionThe cognition on the 5 related knowledge of TB among freshmen is unbalanced, and the overall awareness rate of the 8 core knowledge of TB among freshmen still needs to be improved. Freshmen who have not heard of TB and have not received TB health education before enrollment are the key intervention groups. It is recommended that institutions make full use of modern multimedia technology, continuously optimize the health education forms, implement precise policies, and strengthen the theoretical and practical health education on TB from the initial entry of freshmen into colleges.

Bone exhibits remarkable self-repair ability without fibrous scars. It is believed that the robust regenerative capacity comes from tissue-resident stem cells, such as skeletal stem cells (SSCs). Roughly, SSC has two niches: bone marrow (BM) and periosteum. BM-SSCs have been extensively studied for years. In contrast, our knowledge about periosteal SSCs (P-SSCs) is quite limited. There is abundant clinical evidence for the presence of stem cell populations within the periosteum. Researchers have even successfully cultured “stem-like” cells from the periosteum in vitro. However, due to the lack of effective markers, it is difficult to evaluate the stemness of real P-SSCs in vivo. Recently, several research teams have developed strategies for the successful identification of P-SSCs. For the first time, we can assess the stemness of P-SSCs from visual evidence. BM-SSCs and P-SSCs not only have much in common but also share distinct properties. Here, we provide an updated review of P-SSCs and their particular responses to bone injury.

Skeletal muscle injuries have bothered doctors and caused great burdens to the public medical insurance system for a long time. Once injured, skeletal muscles usually go through the processes of inflammation, repairing and remodeling. If repairing and remodeling stages are out of balance, scars will be formed to replace injured skeletal muscles. At present, clinicians usually use conventional methods to restore the injured skeletal muscles, such as flap transplantation. However, flap transplantation sometimes needs to sacrifice healthy autologous tissues and will bring extra harm to patients. In recent years, stem cells-based tissue engineering provides us new treatment ideas for skeletal muscle injuries. Stem cells are cells with multiple differentiation potential and have ability to differentiate into adult cells under special condition. Skeletal muscle tissues also have stem cells, called satellite cells, but they are in small amount and new muscle fibers that derived from them may not be enough to replace injured fibers. Bone marrow mesenchymal stem cells (BM-MSCs) could promote musculoskeletal tissue regeneration and activate the myogenic differentiation of satellite cells. Biomaterial is another important factor to promote tissue regeneration and greatly enhance physiological activities of stem cells in vivo. The combined use of stem cells and biomaterials will gradually become a mainstream to restore injured skeletal muscles in the future. This review article mainly focuses on the review of research about the application of BM-MSCs and several major biomaterials in skeletal muscle regeneration over the past decades.

Prostate cancers with mismatch repair deficiency (MMR-d) have aggressive clinical and histological features, and they are potentially responsive to immunotherapy. However, its rarity prevents the analysis of the underlying biology. Here, we collected the genomic data of 2664 primary prostate tumors and 1409 metastatic prostate tumors from the GENIE and TCGA databases. A total of 69 (2.59%) primary and 60 (4.26%) metastatic MMR-d tumors were identified among these tumors. Single nucleotide variant (SNV) frequencies of 34 candidate genes (including KMT2D (46.4%), ZFHX3 (33.3%), JAK1 (31.9%), and RNF43 (27.5%)) and 16 candidate genes (including KMT2D (33.3%) and JAK1 (28.3%)) were higher in MMR-d primary tumors and MMR-d metastatic tumors, respectively. The tumor mutation burden (TMB) was higher in primary MMR-d tumors. Homozygous deletions of EPCAM and EPAS1 were enriched in MMR-d primary tumors, while EPCAM deletions were enriched in metastatic MMR-d tumors. For genomic rearrangement events, TMPRSS2-ETS fusions were less frequent in primary MMR-d tumors. Our study indicates MMR-d prostate cancers have unique genomic features. These may play an important role in providing therapeutic targets for the treatment of this subset of prostate cancer patients.

Three adsorbents, trichosanthes kirilowii maxim shell activated carbon (TKAC), nickel alginate/activated carbon (NA/AC) aerogel and nickel alginate/graphene oxide (NA/GO) aerogel were prepared in the present study. The three-dimensional network structure of the NA/AC aerogel and NA/GO aerogel was found to effectively control the dispersion state of TKAC and GO. The adsorption behavior was systematically investigated in terms of adsorption temperature and time, initial adsorbate pH and concentration, as well as the dose of adsorbents. The methylene blue (MB) adsorption process of TKAC was in accordance with the Langmuir isotherm model and followed a pseudo-second order mechanism. The adsorbing capacity of TKAC was 505.050 mg/g at 303 K while the BET surface area was 349.400 m2/g. Thermodynamic analysis demonstrated the spontaneous and endothermic properties of the entire adsorption process. The MB adsorption of the NA/AC aerogel satisfied the Langmuir isotherm and Freundlich isotherm models. Moreover, the MB adsorption on the NA/AC aerogel followed a pseudo-second order mechanism. The adsorbing capacity of the NA/AC aerogel was observed to be 465.120 mg/g at 303 K while the BET surface area was 100.690 m2/g. Thermodynamic investigation demonstrated a spontaneous and exothermic nature of the overall adsorption process. The MB adsorption of the NA/GO aerogel aligned with the Langmuir isotherm model and followed pseudo-second order mechanism. The adsorbing capacity of NA/GO aerogel was found to be 537.630 mg/g at 303 K, while the BET surface area was 5.050 m2/g. Furthermore, thermodynamic studies exhibited spontaneous and exothermic properties of the entire adsorption process.

DsbA-L upregulation prevents lipid-induced renal injury in diabetic nephropathy. Here, the authors show that DsbA-L knockout attenuates tubulointerstitial fibrosis in mice, and show that this occurs via activation of Smad3 and p53, which result in modulation of CTGF, a regulator of kidney fibrosis.

The alumina content of iron ores for sintering is gradually increasing with the growing depletion of high-grade iron ores, which is harmful to the sintering process. Therefore, it is essential to reveal the action mechanism of alumina on sinter quality. In this paper, the aluminum occurrence of various iron ores was determined by applying X-ray diffraction (XRD), optical microscopy, scanning electron microscopy and energy dispersive spectrum analysis (SEM-EDS). Then, the effects of iron ore type, aluminum occurrence (free alumina, gibbsite, diaspore, alumogoethite and kaolinite) and alumina content on formation characteristics of SFCA bonding phases as well as sinter matrix strength were investigated based on laboratory compact sintering tests. The results show that the discrepancy of aluminum occurrence contributes to different SFCA formation characteristics and then sinter matrix strength, due to different reactivity of various aluminum-containing minerals with iron oxides and fluxes. Increasing alumina content generally results in an increase in the porosity of sinters and deterioration of sinter matrix strength for all aluminum occurrence. Aluminum in the form of kaolinite is more conducive to form dendritic or acicular SFCA with superior sinter matrix strength compared with other aluminum occurrences. In contrast, aluminum occurring in free alumina presents greatest adverse impacts on sinter matrix strength due to its poor reactivity and high porosity of resultant sinters.

Summary: Background: we demonstrated that disulfide-bond A oxidoreductase-like protein (DsbA-L) was involved in the progression of renal fibrosis. However, the precise function of DsbA-L in acute kidney injury (AKI), and the mechanisms involved, have yet to be elucidated. Methods: We illustrate the DsbA-L interacted with VDAC1 by co-IP (co-immunoprecipitation) in vitro and vivo, and found the interaction parts of them by mutation experiment. The above findings were verified by co-localization of them. In addition, we constructed the two model of PT-DsbA-L and VDAC1 KO mice to verify the function of DsbA-L and VDAC1 in models of VAN, CLP and I/R-induced AKI. Findings: The PT-DsbA-L-KO mice showed amelioration of I/R, VAN-, and CLP-induced AKI progression via the downregulation of VDAC1. Finally, we confirmed these changes in signal molecules by examining in HK-2 cells and kidney biopsies taken from patients with ischemic or acute interstitial nephritis (AIN)-induced AKI. Mechanistically, DsbA-L interacted with amino acids 9–13 and 22–27 of VDAC1 in the mitochondria of BUMPT cells to induce renal cell apoptosis and mitochondrial injury. Interpretation: This work suggested that DsbA-L, located in the proximal tubular cells, drives the progression of AKI, by directly upregulating the levels of VDAC1.Running Title: The role of DsbA-L in AKI Funding: National Natural Science Foundation of China, a grant from Key Project of Hunan provincial science and technology innovation, Department of Science and Technology of Hunan Province project of International Cooperation and Exchanges, Changsha Science and Technology Bureau project, Natural Science Foundation of Hunan Province, Fundamental Research Funds for the Central Universities of Central South University, Hunan Provincial Innovation Foundation For Postgraduate China Hunan Provincial Science and Technology Department.

Neuroblastoma (NB) is the most common solid tumor of the neural crest cell origin in children and has a poor prognosis in high-risk patients. The oncogene MYCN was found to be amplified at extremely high levels in approximately 20% of neuroblastoma cases. In recent years, research on the targeted hydrolysis of BRD4 to indirectly inhibit the transcription of the MYCN created by proteolysis targeting chimaera (PROTAC) technology has become very popular. dBET57 (S0137, Selleck, TX, USA) is a novel and potent heterobifunctional small molecule degrader based on PROTAC technology. The purpose of this study was to investigate the therapeutic effect of dBET57 in NB and its potential mechanism. In this study, we found that dBET57 can target BRD4 ubiquitination and disrupt the proliferation ability of NB cells. At the same time, dBET57 can also induce apoptosis, cell cycle arrest, and decrease migration. Furthermore, dBET57 also has a strong antiproliferation function in xenograft tumor models in vivo. In terms of mechanism, dBET57 targets the BET protein family and the MYCN protein family by associating with CRBN and destroys the SE landscape of NB cells. Combined with RNA-seq and ChIP-seq public database analysis, we identified the superenhancer-related genes TBX3 and ZMYND8 in NB as potential downstream targets of dBET57 and experimentally verified that they play an important role in the occurrence and development of NB. In conclusion, these results suggest that dBET57 may be an effective new therapeutic drug for the treatment of NB.

More and more evidence suggests the oncogenic function of overexpressed CDC28 protein kinase regulatory subunit 2 (CKS2) in various human cancers. However, CKS2 has rarely been studied in cervical cancer. Herein, taking advantage of massive genetics data from multicenter RNA-seq and microarrays, we were the first group to perform tissue microarrays for CKS2 in cervical cancer. We were also the first to evaluate the clinical significance of CKS2 with large samples (980 cervical cancer cases and 422 noncancer cases). We further excavated the mechanism of the tumor-promoting activities of CKS2 in cervical cancer through analysis of genetic mutation profiles, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) significant enrichment of genes coexpressed with CKS2. According to the results, expression data from multilevels unanimously supported the overexpression of CKS2 in cervical cancer. Patients with cervical cancer in stage II from inhouse microarrays had significantly higher expression of CKS2, and CKS2 overexpression had an adverse impact on the disease-free survival status of cervical cancer patients in GSE44001. Both mutation types of mRNA high and mRNA low appeared in cervical cancer cases from the TCGA Firehose project. Gene coexpressed with CKS2 participated in pathways including the cell cycle, estrogen signaling pathway, and DNA replication. In summary, upregulated CKS2 is closely associated with the malignant clinical development of cervical cancer and might serve as a valuable therapeutic target in cervical cancer.

Background. AML (acute myeloid leukemia) is a common hematological malignancy in children with poor treatment effects and poor prognosis. Recent studies have shown that as a novel BRD4 (bromodomain containing 4) PROTACs (proteolysis targeting chimeras) degrader, GNE-987 can slow down the growth of various tumors and increase apoptosis, with promising clinical prospects. However, the function and molecular mechanism of GNE-987 in AML remain unclear. This study is aimed at investigating the therapeutic effect of GNE-987 on AML and its underlying mechanism. Methods. The association between BRD4 and AML was assessed by studying public databases. After GNE-987 was added to AML cells, cell proliferation slowed down, the cycle was disturbed, and apoptosis increased. Western blotting was used to detect BRD2 (bromodomain containing 2), BRD3 (bromodomain containing 3), BRD4, and PARP (poly ADP-ribose polymerase) proteins. The effect of GNE-987 on AML cells was analyzed in vivo. RNA-seq (RNA sequencing) and ChIP-seq (chromatin immunoprecipitation sequencing) validated the function and molecular pathways of GNE-987 in processing AML. Results. BRD4 expression was significantly elevated in pediatric AML samples compared with healthy donors. GNE-987 inhibited AML cell proliferation by inhibiting the cell cycle and inducing apoptosis. BRD2, BRD3, and BRD4 were consistent with decreased VHL (Von Hippel Lindau) expression in AML cells. In an AML xenograft model, GNE-987 significantly reduced the hepatosplenic infiltration of leukemia cells and increased the mouse survival time. Based on analysis of RNA-seq and ChIP-seq analyses, GNE-987 could target multiple SE- (super-enhancer-) related genes, including LYL1 (lymphoblastic leukemia 1), to inhibit AML. Conclusions. GNE-987 had strong antitumor activity in AML. GNE-987 could effectively inhibit the expression of SE-related oncogenes including LYL1 in AML. Our results suggested that GNE-987 had broad prospects in the treatment of AML.

Direct reduction-magnetic separation process (DRMSP) is a highly effective and clean method to upgrade the complex resources, which has been widely used to recovery the value metals in copper slag (CS) and nickel laterite (NL) in recent years. Adequate growth of the alloy particles is a key parameter influencing the complete extraction of alloys from CS and NL in this process. Therefore, the liquid phase formation mechanism, growth kinetics of the alloy particles, and the correlation between the alloy particle growth and liquid phase formation were studied to reveal the synergistic effect of the co-reduction of CS and NL. The results indicated that fayalite in the copper slag reacted with forsterite in nickel laterite to form augite group minerals with low melting points, resulting in more liquid phase formation in the reductive roasting process. A comparison with the reduction kinetic parameters of the single nickel laterite showed that the growth index and activation energy decreased significantly from 2.85 and 272.98 KJ/mol to 2.08 and 171.99 KJ/mol, respectively, after the addition of 40% copper slag, which confirmed that copper slag promoted the particle growth. Moreover, the liquid phase increased the total cohesive force between the alloy particles, revealing the correlation between alloy particle growth and liquid phase.