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Key points Preeclampsia (PE) is a hypertensive disorder during human pregnancy. Aryl hydrocarbon receptor (AhR) is a ligand‐activated transcription factor. Exogenous and endogenous AhR ligands can induce hypertension in male rats and mice. Herein, using rats as a model, we tested the hypothesis that over‐regulation of endogenous AhR ligands during pregnancy impairs vascular functions by disrupting the transcriptome in the placenta, contributing to the development of PE. Pregnant rats were injected daily with an endogenous AhR ligand, 2‐(1′H‐indole‐3′‐carbonyl)‐thiazole‐4‐carboxylic acid methyl ester (ITE), from gestational day (GD) 10 to 19. Maternal mean blood pressure was measured on GD16–20. Proteinuria and uteroplacental blood flow were monitored on GD20. Placentas collected on GD20 were used to determine changes in vascular density and transcriptome. Compared with the vehicle control, ITE elevated maternal mean blood pressure by 22% and 16% on GD16 and 17, respectively. ITE increased proteinuria by 50% and decreased uteroplacental blood flow by 26%. ITE reduced the placental vascular density by 18%. RNA sequencing analysis revealed that ITE induced 1316 and 2020 differentially expressed genes (DEGs) in female and male placentas, respectively. These DEGs were enriched in pathways relevant to heart diseases, vascular functions and inflammation. Bioinformatics analysis also predicted that ITE altered immune cell infiltration in placentas depending on fetal sex. These data suggest that over‐regulation of endogenous AhR ligands may lead to PE with impaired vascular functions and disrupted fetal sex‐specific transcriptomes and immune cell infiltration in placentas. These AhR ligand‐induced DEGs and pathways may represent promising therapeutic targets for PE‐induced cardiovascular dysfunctions. An endogenous AhR ligand (ITE) elevated maternal blood pressure and proteinuria in pregnant rats, and decreased uteroplacental blood flow and fetal and placental growth, all of which are hallmarks of preeclampsia. ITE reduced vascular density and altered immune cell distribution in rat placentas. ITE dysregulated transcriptomes in rat placentas in a fetal sex‐specific manner. These ITE‐dysregulated genes and pathways are highly relevant to diseases of heart, vascular functions and inflammatory responses. [ABSTRACT FROM AUTHOR]

Background: Psychosocial risk factors (PSRFs) have emerged as important nontraditional risk factors for poor medical outcomes but have not been well‐studied in the field of hematopoietic stem cell transplantation (HSCT). Objectives: In this study, we retrospectively examined in‐hospital and short‐term outcomes in patients with PSRFs who underwent HSCT. Methods: We used the National Readmission Database (NRD) to identify patients who underwent HSCT between 2011 and 2020. Patients were stratified based on the presence of either 0 or ≥ 1 PSRFs, which included factors such as mental illness, substance abuse, cognitive problems, a low income level, and an uninsured status. Patients were also classified into allogeneic‐HSCT (allo‐HSCT) and autologous‐HSCT (auto‐HSCT) groups. Our primary endpoints were in‐hospital and short‐term outcomes. Results: In this nationally representative cohort, 90,747 patients underwent auto‐HSCT, while 26,600 patients underwent allo‐HSCT. In the auto‐HSCT group, individuals with PSRFs exhibited notably higher in‐hospital mortality (2.4% vs. 2.8%; p < 0.001) and 30‐day all‐cause readmission rates (14.4% vs. 17.8%; p < 0.001) compared to those without PSRFs. Similarly, within the allo‐HSCT group, patients with PSRFs had significantly higher in‐hospital mortality (5.4% vs. 6.4%; p < 0.001) and 30‐day all‐cause readmission rates (27.3% vs. 31.2%; p < 0.001) compared to those without PSRFs. After adjusting for risk factors, the presence of PSRFs emerged as a substantial predictor for heightened 30‐day readmission in allo‐HSCT and auto‐HSCT. Conclusion: The presence of PSRFs is correlated with poorer in‐hospital and short‐term outcomes after both allo‐HSCT and auto‐HSCT, with a more pronounced effect observed in allo‐HSCT. This research underscores the significance of pinpointing high‐risk patients and implies support for merging PSRFs after HSCT is beneficial. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Design Sample Measure Results Conclusion: Compliance is crucial for patients to control and manage their high blood pressure. This study assesses the compliance levels of hypertensive patients in China and explores the factors influencing compliance.A descriptive, cross‐sectional design was conducted.A total of 371 hypertensive patients were recruited from six County hospitals and 12 township health centers in Zhejiang Province, China.Patient compliance was measured using the Hypertensive Patient Scale (CHPS). Independent‐sample T‐test or variance analysis was applied to analyze CHPS scores by sociodemographic factors, and linear regression was used to explore the significant correlates of the total CHPS score.The total score of CHPS was 50.18 ± 6.12. Among the seven domains, drug treatment and lifestyle had the highest and lowest average scores, 3.59 ± 0.87 and 2.74 ± 0.73, respectively. The total score of CHPS positively associated with age (β = 0.075, p = 0.028), > 7 years of hypertension (β = 1.896, p = 0.022; Ref: < 3 years), and negatively associated with males (β = −2.224, p = 0.001; Ref: female) and rural area (β = −2.008, p = 0.007; Ref: urban area).These findings highlight the importance of related measurements of the local “health‐oriented” healthcare system. Primary health professionals should strengthen their health behavior intervention capacity and improve hypertension management among their patients. [ABSTRACT FROM AUTHOR]

Objective: To enhance the accuracy in predicting lymph node metastasis (LNM) preoperatively in patients with papillary thyroid microcarcinoma (PTMC), refining the "low‐risk" classification for tailored treatment strategies. Methods: This study involves the development and validation of a predictive model using a cohort of 1004 patients with PTMC undergoing thyroidectomy along with central neck dissection. The data was divided into a training cohort (n = 702) and a validation cohort (n = 302). Multivariate logistic regression identified independent LNM predictors in PTMC, leading to the construction of a predictive nomogram model. The model's performance was assessed through ROC analysis, calibration curve analysis, and decision curve analysis. Results: Identified LNM predictors in PTMC included age, tumor maximum diameter, nodule‐capsule distance, capsular contact length, bilateral suspicious lesions, absence of the lymphatic hilum, microcalcification, and sex. Especially, tumors larger than 7 mm, nodules closer to the capsule (less than 3 mm), and longer capsular contact lengths (more than 1 mm) showed higher LNM rates. The model exhibited AUCs of 0.733 and 0.771 in the training and validation cohorts respectively, alongside superior calibration and clinical utility. Conclusion: This study proposes and substantiates a preoperative predictive model for LNM in patients with PTMC, honing the precision of "low‐risk" categorization. This model furnishes clinicians with an invaluable tool for individualized treatment approach, ensuring better management of patients who might be proposed observation or ablative options in the absence of such predictive information. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is one of the global burdens of disease, and its pathogenesis remains unclear. An increasing amount of research indicates that ghrelin regulates mood in patients with MDD. Still, current results are inconsistent, and the mechanisms underlying how ghrelin modulates depressive symptoms are inconclusive, especially in first‐episode drug‐naïve MDD patients. Therefore, this study aims to investigate the relationship and potential mechanism between ghrelin and first‐episode drug‐naïve MDD. Methods: Ninety first‐episode drug‐naïve MDD patients and 65 healthy controls (HCs) were included. Hamilton Depression Scale (HAMD‐17) as a measure of depressive symptoms. Plasma levels of ghrelin and hypothalamic–pituitary–adrenal axis (HPA‐axis) hormones were measured in all participants. Results: Compared to HCs, the ghrelin levels were higher in the MDD (p <.001) and still showed significance after covarying for sex, age, and Body Mass Index (BMI). Ghrelin was positively related to corticotropin‐releasing‐hormone (CRH) levels (r =.867, p <.001), adrenocorticotropic hormone (ACTH) levels (r =.830, p <.001), and cortisol levels (r =.902, p <.001) in partial correlation analysis. In addition, there was a positive correlation between HAMD total score and ghrelin levels (r =.240, p =.026). Other than that, the HAMD total score also had a positive correlation with the CRH (r =.333, p =.002) and cortisol (r =.307, p =.004) levels. Further mediation analysis demonstrated that the relationship between ghrelin and HAMD total score was mediated by CRH (ab‐path; β =.4457, 95% CI = 0.0780–1.0253, c‐path; β =.2447, p =.0260, c′‐path; β = −.2009, p =.3427). Conclusions: These findings revealed that plasma ghrelin provides a pivotal link to depressive symptoms in first‐episode drug‐naive MDD patients. CRH mediated the relationship between ghrelin and HAMD total score. It might provide new insights into understanding the pathogenesis of MDD, contributing to intervention and treatment from this approach. [ABSTRACT FROM AUTHOR]

Objectives: The collapse of femoral head is a serious symptom of osteonecrosis of the femoral head (ONFH), resulting in hip pain and deformity. However, it is hardly possible to reestablish the femoral head nonoperatively once the collapse happens. Predicting femoral head collapse is of great value for the prognosis of ONFH. This study aimed to develop a new method to quantify the preserved thickness of femoral head and to assess its diagnostic contribution in predicting femoral head collapse on plain radiographs. Methods: This was a single‐center retrospective study. A total of 101 hips (85 patients) with ARCO stage II from January 2008 to December 2016 were included in this study. The preserved thickness was measured on standard anteroposterior (AP) and frog‐leg (FL) radiographs. The anteroposterior view's preserved thickness ratio (APTR) and the frog‐leg view's preserved thickness ratio (FPTR) were calculated to show the preserved thickness ratio of the femoral head anteriorly and laterally. Univariate and multivariate logistic regression was performed to determine the risk factors for collapse. Sensitivity, specificity, and cut‐off values for APTR and FPTR were determined by the receiver operating characteristic (ROC) curve analysis. Kaplan–Meier (K‐M) analysis was applied to determine femoral head survival in ONFH patients. Results: The mean age of the 27 females and 58 males was 38.93 years old. The mean follow‐up time was 74.62 (36–124) months in the non‐collapse group and 18.66 (3–82) months in the collapse group. Femoral head collapse was observed in 62 hips during the follow‐up period. Logistic regression analysis and ROC results showed that APTR <24.79% and FPTR <10.62% were significantly correlated with femoral head collapse. The Kaplan–Meier survival curve suggested that the overall survival rate of APTR ≥24.79% was 68.2% at 5 and 10 years and FPTR ≥10.62% was 71.63% at 5 and 10 years. At the last follow‐up, 26 hips had collapse on the anterior side of the femoral head, 12 hips occurred on the lateral side, and 24 hips happened to collapse on both anterior and lateral sides. Conclusion: Femoral head collapse predominantly occurred anteriorly rather than laterally in ONFH patients. The measurements of APTR and FPTR have noticeable implications for the prediction of femoral head collapse, and contribute to the selection of treatment options for ONFH patients with types B and C1 according to the JIC classification. [ABSTRACT FROM AUTHOR]

Lithium–carbon dioxide (Li–CO2) battery technology presents a promising opportunity for carbon capture and energy storage. Despite tremendous efforts in Li–CO2 batteries, the complex electrode/electrolyte/CO2 triple‐phase interfacial processes remain poorly understood, in particular at the nanoscale. Here, using in situ atomic force microscopy and laser confocal microscopy‐differential interference contrast microscopy, we directly observed the CO2 conversion processes in Li–CO2 batteries at the nanoscale, and further revealed a laser‐tuned reaction pathway based on the real‐time observations. During discharge, a bi‐component composite, Li2CO3/C, deposits as micron‐sized clusters through a 3D progressive growth model, followed by a 3D decomposition pathway during the subsequent recharge. When the cell operates under laser (λ=405 nm) irradiation, densely packed Li2CO3/C flakes deposit rapidly during discharge. Upon the recharge, they predominantly decompose at the interfaces of the flake and electrode, detaching themselves from the electrode and causing irreversible capacity degradation. In situ Raman shows that the laser promotes the formation of poorly soluble intermediates, Li2C2O4, which in turn affects growth/decomposition pathways of Li2CO3/C and the cell performance. Our findings provide mechanistic insights into interfacial evolution in Li–CO2 batteries and the laser‐tuned CO2 conversion reactions, which can inspire strategies of monitoring and controlling the multistep and multiphase interfacial reactions in advanced electrochemical devices. [ABSTRACT FROM AUTHOR]

Objectives: Intratumor heterogeneity (ITH) is an important factor for clinical outcomes in patients with multiple myeloma (MM). High ITH has been proven to be a key reason for tumor immune escape and treatment resistance. Neoantigens are thought to be associated with ITH, but the specific correlation and functional basis for this remains unclear. Methods: We study this question through the whole‐exome sequencing (WES) data from 43 high ITH newly diagnosed MM patients in our center. Mutant allele tumor heterogeneity (MATH) was conducted to quantify ITH. The cutoff value for high intratumor heterogeneity was determined by comparing MATH of different kinds of tumors. NeoPredPipe was performed to predict neoantigens and binding affinity. Results: Compared to other tumors, MM has a relatively low tumor mutation burden but a high ITH. Patients with high MATH had significantly shorter progression‐free survival times than those with low MATH (p = 0.001). In high ITH samples, there is a decrease in strong‐binding neoantigens (p = 0.019). The loss of strong‐binding neoantigens is a key factor for insensitivity to therapy (p = 0.015). Loss of heterozygosity in HLA was not observed. In addition, patients with fewer neoantigens loss had higher rates of disease remission (p = 0.047). CD8 + T cells (p = 0.012) and NK cells (p = 0.011) decreased significantly in patients with high neoantigens loss rate. A prediction model based on neoantigens was built to evaluate the strength of immune escape. Conclusion: The loss of strong‐binding neoantigens explains why tumors with high ITH have a higher degree of immune escape and may be feasible for deciding the clinical treatment of MM. [ABSTRACT FROM AUTHOR]

Objectives. To study trends of utilization, in-hospital outcomes, and short outcomes in patients undergoing transcatheter mitral valve repair (TMVR) vs. surgical mitral valve repair (SMVR) in atrial fibrillation (AF). Background. TMVR is a treatment option in inoperable or high-risk patients with mitral regurgitation (MR). AF is a common comorbidity of MR. Data comparing between TMVR and SMVR in MR patients with AF is lacking. Methods. The National Readmission Database from 2016 to 2019 was utilized to identify hospitalizations undergoing TMVR or SMVR with AF. Outcomes of interest included mortality, postoperative complications, length of stay, and 30-day readmission rate. Results. A total of 9,195 patients underwent TMVR and 16,972 patients underwent SMVR with AF; the number of AF undergoing TMVR was increasing from 1,342 in 2016 to 4,215 in 2019 and SMVR. The incidence of in-hospital mortality decreased from 2.6% in 2016 to 1.8% in 2019. We identified length of stay>5 days, dyslipidemia, cerebrovascular disease, heart failure with reduced ejection fraction, and urgent/emergent admissions as independent risk factors for in-hospital mortality. After matching, we included 4,680 patients in each group; the in-hospital death, transfusion, acute kidney injury, sepsis, stroke, and mechanical ventilation were lower in TMVR compared with SMVR. TMVR was associated with a similar rate of all-cause readmission at 30 days compared with SMVR. Conclusion. Patients with AF receiving TMVR have been increasing along with progressive improvement in in-hospital death and length of stay. Compared to SMVR, AF patients receiving TMVR had a lower rate of in-hospital death and postoperative complications. [ABSTRACT FROM AUTHOR]

Oxaliplatin is a widely used chemotherapy drug for patients with advanced colorectal cancer (CRC); however, frequent drug resistance limits its therapeutic efficacy in patients. Here, this work identifies cyclin‐dependent kinase 1 (CDK1) as a critical contributor to oxaliplatin resistance via in vitro and in vivo CRISPR/Cas9 screening. CDK1 is highly expressed in oxaliplatin‐resistant cells and tissues due to the loss of N6‐methyladenosine modification. Genetic and pharmacological blockade of CDK1 restore the susceptibility of CRC cells to oxaliplatin in vitro and in cell/patient‐derived xenograft models. Mechanistically, CDK1 directly binds to and phosphorylates Acyl‐CoA synthetase long‐chain family 4 (ACSL4) at S447, followed by recruitment of E3 ubiquitin ligase UBR5 and polyubiquitination of ACSL4 at K388, K498, and K690, which leads to ACSL4 protein degradation. Reduced ACSL4 subsequently blocks the biosynthesis of polyunsaturated fatty acid containing lipids, thereby inhibiting lipid peroxidation and ferroptosis, a unique iron‐dependent form of oxidative cell death. Moreover, treatment with a ferroptosis inhibitor nullifies the enhancement of CRC cell sensitivity to oxaliplatin by CDK1 blockade in vitro and in vivo. Collectively, the findings indicate that CDK1 confers oxaliplatin resistance to cells by suppressing ferroptosis. Therefore, administration of a CDK1 inhibitor may be an attractive strategy to treat patients with oxaliplatin‐resistant CRC. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) differentially impairs female and male fetal endothelial cell function, which is associated with an increased risk of adult‐onset cardiovascular disorders in children born to mothers with PE. However, the underlying mechanisms are poorly defined. We hypothesize that dysregulation of microRNA‐29a‐3p and 29c‐3p (miR‐29a/c‐3p) in PE disturbs gene expression and cellular responses to cytokines in fetal endothelial cells in a fetal sex‐dependent manner. RT‐qPCR analysis of miR‐29a/c‐3p was performed on female and male unpassaged (P0) human umbilical vein endothelial cells (HUVECs) from normotensive (NT) pregnancies and PE. Bioinformatic analysis of an RNA‐seq dataset was performed to identify PE‐dysregulated miR‐29a/c‐3p target genes in female and male P0‐HUVECs. Gain‐ and loss‐of‐function assays were conducted to determine the effects of miR‐29a/c‐3p on endothelial monolayer integrity and proliferation in response to transforming growth factor‐β1 (TGFβ1) and tumour necrosis factor‐α (TNFα) in NT and PE HUVECs at passage 1. We observed that PE downregulated miR‐29a/c‐3p in male and female P0‐HUVECs. PE dysregulated significantly more miR‐29a/c‐3p target genes in female vs. male P0‐HUVECs. Many of these PE‐differentially dysregulated miR‐29a/c‐3p target genes are associated with critical cardiovascular diseases and endothelial function. We further demonstrated that miR‐29a/c‐3p knockdown specifically recovered the PE‐abolished TGFβ1‐induced strengthening of endothelial monolayer integrity in female HUVECs, while miR‐29a/c‐3p overexpression specifically enhanced the TNFα‐promoted cell proliferation in male PE HUVECs. In conclusion, PE downregulates miR‐29a/c‐3p expression and differentially dysregulates miR‐29a/c‐3p target genes associated with cardiovascular diseases and endothelial function in female and male fetal endothelial cells, possibly contributing to the fetal sex‐specific endothelial dysfunction observed in PE. Key points: Preeclampsia differentially impairs female and male fetal endothelial cell function in responses to cytokines. Pro‐inflammatory cytokines are elevated in maternal circulation during pregnancy in preeclampsia.MicroRNAs are critical regulators of endothelial cell function during pregnancy. We have previously reported that preeclampsia downregulated microRNA‐29a‐3p and 29c‐3p (miR‐29a/c‐3p) in primary fetal endothelial cells. However, it is unknown if PE differentially dysregulates the expression of miR‐29a/c‐3p in female and male fetal endothelial cells.We show that preeclampsia downregulates miR‐29a/c‐3p in male and female HUVECs and preeclampsia dysregulates cardiovascular disease‐ and endothelial function‐associated miR‐29a/c‐3p target genes in HUVECs in a fetal sex‐specific manner.MiR‐29a/c‐3p differentially mediate cell responses to cytokines in female and male fetal endothelial cells from preeclampsia.We have revealed fetal sex‐specific dysregulation of miR‐29a/c‐3p target genes in fetal endothelial cells from preeclampsia. This differential dysregulation may contribute to fetal sex‐specific endothelial dysfunction in offspring born to preeclamptic mothers. [ABSTRACT FROM AUTHOR]

Background: Significant advances in multiple myeloma (MM) over the past 15 years led to exciting changes in the management of MM patients in China, which in turn brought about the early diagnoses, precise risk stratifications, and improved prognoses. Methods: We summarized the dynamic changes in the management of newly diagnosed (ND) MM in a national medical center, crossing the old and novel drug era. Demographics, clinical characteristics, first‐line treatment, response rate, and survival were retrospectively collected among NDMMs diagnosed in Zhongshan Hospital Fudan University from January 2007 to October 2021. Results: Of the 1256 individuals, median age was 64 (range 31–89) with 45.1% patients >65 years. About 63.5% were male, 43.1% were at ISS stage III and 9.9% had light‐chain amyloidosis. Patients with abnormal ratio of free light chain (80.4%), extramedullary disease (EMD, 22.0%), and high‐risk cytogenetic abnormalities (HRCA, 26.8%) were detected by novel detection techniques. The best confirmed ORR was 86.5%, including 39.4% with CR. Short‐ and long‐term PFS and OS rates persistently increased each year along with increasing novel drug applications. Median PFS and OS were 30.9 and 64.7 months. Advanced ISS stage, HRCA, light‐chain amyloidosis and EMD independently predicted an inferior PFS. First‐line ASCT indicated a superior PFS. Advanced ISS stage, elevated serum LDH, HRCA, light‐chain amyloidosis, and receiving PI/IMiD‐based regimen versus PI+IMiD‐based regimen independently indicated a poorer OS. Conclusions: In brief, we illustrated a dynamic landscape of MM patients in a national medical center. Chinese MM patients evidently benefited from newly introduced techniques and drugs in this field. [ABSTRACT FROM AUTHOR]

Background: The prognostic value of additional copies of chromosome 1q (1q gain/amplification [amp]) in multiple myeloma (MM) remains controversial. In the meantime, the kinetics of the response to MM therapy has long been an area of debate. Few studies have pointed out the relationship of response kinetics with cytogenetic abnormalities (CAs) in MM. Methods: The authors retrospectively analyzed the data of 1068 real‐world newly diagnosed MM patients from a Chinese national medical center. Results: Overall, 405 (51.9%) patients had 1q gain/amp, with aggressive clinical characteristics and significant inferior survival. The variation in copy number (CN) of 1q (CN = 3 or CN >3) had no significant impact on the survival of MM patients with 1q abnormalities. No difference was found in the outcome of 1q gain/amp patients treated with doublet or triplet regimens. Upfront autologous stem cell transplantation could eliminate the adverse prognostic effect of 1q gain but not 1q amp. The duration from diagnosis to the first time achieving very good partial response (VGPR) or better was significantly shorter in patients with 1q gain/amp (77 days vs. 100 days, p =.001). Finally, multifactor regression analysis was performed to construct a new risk stratification model in MM patients with 1q gain/amp, which was validated in the Multiple Myeloma Research Foundation CoMMpass study cohort and worked better than the Revised International Staging System and Second Revision of the International Staging System (Harrell's concordance index: 0.631 vs. 0.598 and 0.537). Conclusions: In the setting of novel therapy, 1q gain/amp still acts as an independent adverse prognostic factor. Patients with 1q gain/amp achieved VGPR rapidly but had inferior survival. 1q gain/amplification (amp) still acts as an independent adverse prognostic factor even in the setting of novel therapy. Patients with 1q gain/amp achieved very good partial response rapidly, but they could not achieve a deep response and consequently had inferior survival. [ABSTRACT FROM AUTHOR]

Advanced materials, electrically conductive and oxidation resistant, are frontrunners for technological advancements in cutting‐edge high‐temperature electronics. Rational design and manufacturing of hierarchical material structures is indispensable to achieve such disparate functionalities. Here, high‐temperature copper–graphene conductors, through additive manufacturing, which prohibits oxygen adsorbates and serves as the barrier for oxygen migration to enable electric stability and reliability at high temperatures, are reported. The combination of graphene and alumina surface passivation enables the electric stability of copper–graphene under thermal impact above 1000 °C. The findings shown here, the synergistic combination of high conductivity and oxidation resistance, enunciate the passivation capabilities for additively manufactured flexible electronics operating under harsh conditions. [ABSTRACT FROM AUTHOR]

The roles of oncogenic KRAS in tumor immune evasion remain poorly understood. Here, mutant KRAS is identified as a key driver of tumor immune evasion in colorectal cancer (CRC). In human CRC specimens, a significant reduction in cytotoxic CD8+ T‐cell tumor infiltration is found in patients with mutant versus wild type KRAS. This phenomenon is confirmed by preclinical models of CRC, and further study showed KRAS mutant tumors exhibited poor response to anti‐PD‐1 and adoptive T‐cell therapies. Mechanistic analysis revealed lactic acid derived from mutant KRAS‐expressing tumor cells sensitized tumor‐specific cytotoxic CD8+ T‐cells to activation‐induced cell death via NF‐κB inactivation; this may underlie the inverse association between intratumoral cytotoxic CD8+ T‐cells and KRAS mutation. Importantly, KRAS mutated tumor resistance to immunotherapies can be overcome by inhibiting KRAS or blocking lactic acid production. Together, this work suggests the KRAS‐mediated immune program is an exploitable therapeutic approach for the treatment of patients with KRAS mutant CRC. [ABSTRACT FROM AUTHOR]

The piezo‐Fenton system has attracted attention not only because it can enhance the Fenton reaction activity by mechanical energy input, but also because it is expected to realize a class of stimuli‐responsive advanced oxidation systems by regulating energy input and hydrogen peroxide self‐supply, thus greatly enriching the application possibilities of Fenton chemistry. In this work, a series of Fe‐doped g‐C3N4 (g‐C3N4‐Fe) as a piezo‐Fenton system were synthesized where the iron stably immobilized through Fe−N interaction. The piezo‐induced electrons generate on g‐C3N4 matrix support the conversion of Fe(III) to Fe(II) and promote rate‐limiting step of Fenton reaction. With the optimal Fe loading, g‐C3N4‐0.5Fe can achieve methylene blue (MB) degradation under ultrasonic treatment with first‐order kinetic rate constants of 75×10−3 min−1. Most importantly, the g‐C3N4‐Fe can maintain good catalytic activity in a wide pH range (pH=2.0∼9.0) and be cyclic used without iron leaching to solution (<0.001 μg ⋅ L−1), overcoming the disadvantage of traditional Fe‐based Fenton catalysts that can only be applied under acidic conditions and prone to secondary pollution. In addition, g‐C3N4‐0.5Fe also exhibits antibacterial properties of Escherichia coli and Staphylococcus aureus under ultrasound. Hydroxyl radicals mainly contribute to the degradation of MB and the sterilization process. Our work is an attempt to clarify the role of g‐C3N4‐Fe in the conversion of mechanical energy to ROS and provide inspirations for the piezo‐Fenton system design. [ABSTRACT FROM AUTHOR]

Objective: Musculoskeletal pain is having growing impacts worldwide with clinical challenge in pain management. The purpose of the present study is to investigate the preferences of orthopedic surgeons of China for using medicine in musculoskeletal pain. Methods: A questionnaire was developed, including the following domains, personal information, medication preference for pain treatment, and perceptions of topical medicine. Ten participants were selected to confirm the consistency of questionnaire. A cross‐sectional survey was conducted in orthopedic physicians with different specialties in different regions of China via the online survey platform. The participants' survey results were analyzed one‐way and multi‐way using chi‐square test and logistic regression. Results: The pre‐survey analysis results of 10 randomly selected investigators were a mean weighted kappa coefficient of 0.76 (range 0.61–0.89), which indicated the substantial consistency of the present questionnaire. A total of 1099 orthopedic surgeons (mean age, 41.67 ± 8.31 years) responded to our survey, most of whom were male (90.72%), and most of whom worked in level III hospitals (63.24%) and trained in modern medicine (71.43%). Most surgeons who participated in the survey had used topical analgesics in their clinical work (95.81%), and most preferred to use topical analgesics (39.50%) or a combination of oral analgesics (28.87%). Primary reasons for preferring topical analgesics were as follows: less adverse reactions (68.01%); ease of use (60.90%); and not interfering with other oral medications (49.60%). The preference for prescribing topical analgesics increased with the education level of the respondent, where statistically significant differences were seen (P < 0.05). In addition, the level of the respondent's hospital, type of hospital, the respondent's profession, and their participation in surgical work influenced their preferences for topical analgesics (P < 0.05). Conclusion: Orthopedic surgeons across China have different medication preferences in the treatment of musculoskeletal pain. The educational background of the physician largely influences the preference when selecting medications. To better improve the treatment of musculoskeletal pain, there is a need to improve the overall medical education of practitioners and to disseminate clinical practice guidelines. [ABSTRACT FROM AUTHOR]

Purpose. The aim of this study is to explore pathological mechanisms of bone fragility in type 2 diabetes mellitus (T2DM) patients. Methods. Identifying common genes for T2DM and osteoporosis by taking the intersection is shared by the Comparative Toxicogenomics Database (CTD), DISEASES, and GeneCards databases. The differentially expressed genes (DEGs) and the differentially expressed miRNAs (DEMs) were identified by analyzing the Gene Expression Omnibus (GEO) datasets (GSE35958, GSE43950, and GSE70318). FunRich and miRNet were applied to predict potential upstream transcription factors and downstream target genes of candidate DEMs, respectively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore potential mechanisms using Metascape. Eventually, a miRNA-gene network was constructed by Cytoscape software. Results. 271 common targets and 35 common DEGs between T2DM and osteoporosis were screened out in the above databases, and a total of ten DEMs were obtained in the GSE70318. SP1 was predicted to potentially regulate most of the DEMs. Enrichment analysis showed the PI3K-Akt signaling pathway and AGE-RAGE signaling pathway in diabetic complications may play an important role in diabetic skeletal fragility. Two genes (NAMPT and IGFBP5) were considered as key genes involving in the development of diabetic osteoporosis. Through the construction of the miRNA-gene network, most of the hub genes were found to be potentially modulated by miR-96-5p and miR-7-5p. Conclusion. The study uncovered several important genes, miRNAs, and pathological mechanisms involved in diabetic skeletal fragility, among which the PI3K-Akt signaling pathway and AGE-RAGE signaling pathway in diabetic complications may play important roles. [ABSTRACT FROM AUTHOR]

Objective: To report the medium‐term outcomes of surgical hip dislocation (SHD) combined with impacting bone grafts and implanting iliac bone flaps in the treatment of osteonecrosis of the femoral head (ONFH) and to define the indications for this treatment. Methods: This was a single‐center retrospective study. In total, 64 patients (70 hips) with ONFH treated from January 2014 to December 2017 were included in this study. There were 51 males and 13 females aged 18–55 years with an average age of 32 years. All patients underwent surgery for SHD combined with impacting bone grafts and implanting iliac bone flaps. Preoperative and postoperative clinical outcomes were assessed. The clinical outcome was assessed using the Harris hip score (HHS) and the conversion rate of total hip arthroplasty (THA). Univariate and multivariate logistic regression analyses were performed to identify risk factors affecting the clinical outcome. Kaplan–Meier (K‐M) analysis was applied to calculate the survival rate of the femoral head. Results: At the last follow‐up (60 ± 15.08 months), the HHS was excellent for 41 hips, good for 17 hips, fair for three hips, and poor for nine hips. All nine hips with poor HHS underwent THA, including five in the first 2 years following the index surgery and four between three and 5 years. The conversion rate of total hip arthroplasty was 12.86%. Univariate and multivariate logistic regression analyses showed that the duration of hip pain and JIC classification type were significantly associated with clinical outcomes. Elderly age and advanced ONFH stage tended to lead to worse surgical outcomes. The overall survival rate of JIC classification type C1 and duration of pain ≤6 months was 98.1% and 97.8% at 72 months, respectively, as estimated by the Kaplan–Meier method. Conclusion: Surgical hip dislocation combined with impacting bone grafts and implanting iliac bone flaps in the treatment of ONFH had a good mid‐term clinical outcome, especially for patients with retention of the lateral column of the femoral head and hip pain less than 1 year. [ABSTRACT FROM AUTHOR]

Additive manufacturing (AM) is a digital manufacturing process that can directly convert a computer‐aided design model into a physical object in a layer‐by‐layer manner. Due to the additive and discrete nature of the digital manufacturing process, AM needs to find a trade‐off between process resolution and production efficiency. Traditional AM processes balance the resolution and efficiency by tuning the processes either in the temporal domain (e.g., higher speed in serial processes) or in the spatial domain (e.g., more tools in parallel processes). To improve the resolution without sacrificing efficiency, a data‐driven mask image planning method based on subpixel shifting in a split second by tuning the process in both temporal and spatial domains is presented. The method is based on the optimized pixel blending principle and a fast error diffusion‐based optimization model. Various simulation and experimental tests are carried out to verify the developed subpixel shifting method. The experimental results demonstrate the data‐driven‐based mask image calibration and planning techniques significantly improve the fabricated part quality without compromising the process efficiency. The presented spatiotemporal strategy may shed light for future research on the projection‐based AM processes. [ABSTRACT FROM AUTHOR]

Dynamic Schottky direct‐current (DC) generators hold great promise for ambient mechanical energy harvesting as it overcomes the low‐current output limitation in conventional approaches. However, the lack of a fundamental understanding of DC generation in conducting polymer‐based Schottky generators has hindered their application for self‐powered wearable and implantable electronics. Here, a high‐performance, flexible Schottky DC generator with metal/conducting polymer sliding contact system is demonstrated, which exhibits a large current density (J) up to 20 A m–2 for single contact geometry and a scaled‐up DC output reaching 200 µA (J = 0.73 A m–2) and 0.8 V. The design of flexibility in such a Schottky DC generator is inherited from the long‐chain polymer concept, leading to the demonstration of a variety of device configuration of free‐standing thin film, supported thin film and nanocomposite prototype toward practical applications. It is revealed that the sliding junctions may exhibit a different mechanical energy conversion mechanism compared to the compressive conducting polymer Schottky junctions. It is also proven that the magnitude and polarity of DC generation is determined by the Schottky contact formation and interfacial electric field. The concept of a flexible Schottky generator not only shows great promise for next‐generation, self‐powered wearable devices, but also provides potential mechanisms for developing novel wearable sensors. [ABSTRACT FROM AUTHOR]

Main observation and conclusion: Using in situ atomic force microscopy, we visualized the oxidation dynamic process of toroidal lithium peroxide (Li2O2) in a working Li‐O2 battery and clarified the correlation between the decomposition behavior and the charging rate. It was found that at a low charge rate, the decomposition could occur at the Li2O2/electrolyte interface, providing strong evidence that a tiny current is allowed to pass through the bulk phase of toroidal Li2O2. Further, the evolution of the periphery thickness, diameter and center thickness of the toroid as a function of charge capacity was quantitatively analyzed. In the early stage of charging, the diameter of the toroid radially shrinks and the shrinking rate slows down in the later stage. Besides, the periphery thickness of the toroid decreases at a faster and uniform rate, while the center thickness decreases obviously in the later stage of charging. Increasing the charging rate promotes the decomposition occurring at the Li2O2/electrode interface, causing direct desorption of the Li2O2 from the electrode and irreversible capacity degradation. [ABSTRACT FROM AUTHOR]

Rhus chinensis Mill. (RCM) is the host plant of Galla chinensis, which is valued in traditional medicine. Environmental temperature directly determines the probability of gallnut formation and RCM growth. At present, there is no experiment to systematically analyse the stability of internal reference gene (RG) expression in RCM. In this experiment, leaves that did not form gallnuts were used as the control group, while leaves that formed gallnuts were used as the experimental group. First, we conducted transcriptome experiments on RCM leaves to obtain 45 103 differential genes and functional enrichment annotations between the two groups. On this basis, this experiment established a transcriptional gene change model of leaves in the process of gallnut formation after being bitten by aphids, and RCM reference candidate genes were screened from RNA sequencing (RNA‐seq) data. This study is based on RCM transcriptome data and evaluates the stability of 11 potential reference genes under cold stress (4 °C) and heat stress (34 °C), using three statistical algorithms (geNorm, NormFinder, and BestKeeper). The results show that GAPDH1 + PP2A2/UBQ are stable reference genes under heat stress, while GAPDH1 + ACT are the most stable under cold stress. This study is the first to screen candidate reference genes in RCM and could help guide future molecular studies in this genus. [ABSTRACT FROM AUTHOR]

Background. Systemic lupus erythematosus (SLE) is a refractory immune disease, which is often complicated with osteonecrosis of the femoral head (ONFH). Curcumin, the most active ingredient of Curcuma longa with a variety of biological activities, has wide effects on the body system. The study is aimed at exploring the potential therapeutic targets underlying the effect of curcumin on SLE-ONFH by utilizing a network pharmacology approach and molecular docking strategy. Methods. Curcumin and its drug targets were identified using network analysis. First, the Swiss target prediction, GeneCards, and OMIM databases were mined for information relevant to the prediction of curcumin targets and SLE-ONFH-related targets. Second, the curcumin target gene, SLE-ONFH shared gene, and curcumin-SLE-ONFH target gene networks were created in Cytoscape software followed by collecting the candidate targets of each component by R software. Third, the targets and enriched pathways were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Eventually, a gene-pathway network was constructed and visualized by Cytoscape software; key potential central targets were verified and checked by molecular docking and literature review. Results. 201 potential targets of curcumin and 170 related targets involved in SLE-ONFH were subjected to network analysis, and the 36 intersection targets indicated the potential targets of curcumin for the treatment of SLE-ONFH. Additionally, for getting more comprehensive and accurate candidate genes, the 36 potential targets were determined to be analyzed by network topology and 285 candidate genes were obtained finally. The top 20 biological processes, cellular components, and molecular functions were identified, when corrected by a P value ≤ 0.05. 20 related signaling pathways were identified by KEGG analysis, when corrected according to a Bonferroni P value ≤ 0.05. Molecular docking showed that the top three genes (TP53, IL6, VEGFA) have good binding force with curcumin; combined with literature review, some other genes such as TNF, CCND1, CASP3, and MMP9 were also identified. Conclusion. The present study explored the potential targets and signaling pathways of curcumin against SLE-ONFH, which could provide a better understanding of its effects in terms of regulating cell cycle, angiogenesis, immunosuppression, inflammation, and bone destruction. [ABSTRACT FROM AUTHOR]

Human leukocyte antigen (HLA) genotyping gains intensive attention due to its critical role in cancer immunotherapy. It is still a challenging issue to generate reliable HLA genotyping results through in silico tools. In addition, the survival impact of HLA alleles in tumor prognosis and immunotherapy remains controversial. In this study, the benchmarking of HLA genotyping on TCGA is performed and a 'Gun‐Bullet' model which helps to clarify the survival impact of HLA allele is presented. The performance of HLA class I genotyping is generally better than class II. POLYSOLVER, OptiType, and xHLA perform generally better at HLA class I calling with an accuracy of 0.954, 0.949, and 0.937, respectively. HLA‐HD obtained the highest accuracy of 0.904 on HLA class II alleles calling. Each HLA genotyping tool displayed specific error patterns. The ensemble HLA calling from the top‐3 tools is superior to any individual one. HLA alleles show distinct survival impact among cancers. Cytolytic activity (CYT) was proposed as the underlying mechanism to interpret the survival impact of HLA alleles in the 'Gun‐Bullet' model for fighting cancer. A strong HLA allele plus a high tumor mutation burden (TMB) could stimulate intensive immune CYT, leading to extended survival. We established an up to now most reliable TCGA HLA benchmark dataset, composing of concordance alleles generated from eight prevalently used HLA genotyping tools. Our findings indicate that reliable HLA genotyping should be performed based on concordance alleles integrating multiple tools and incorporating TMB background with HLA genotype, which helps to improve the survival prediction compared to HLA genotyping alone. [ABSTRACT FROM AUTHOR]

Motion interpolation technology produces transition motion frames between two discrete movements. It is wildly used in video games, virtual reality and augmented reality. In the fields of computer graphics and animations, our data‐driven method generates transition motions of two arbitrary animations without additional control signals. In this work, we propose a novel carefully designed deep learning framework, named deep motion interpolation network (DMIN), to learn human movement habits from a real dataset and then to perform the interpolation function specific for human motions. It is a data‐driven approach to capture overall rhythm of two given discrete movements and generate natural in‐between motion frames. The sequence‐by‐sequence architecture allows completing all missing frames within single forward inference, which reduces computation time for interpolation. Experiments on human motion datasets show that our network achieves promising interpolation performance. The ablation study demonstrates the effectiveness of the carefully designed DMIN.1 [ABSTRACT FROM AUTHOR]

This paper considers two competing supply chains that face cost uncertainty, each consisting of one supplier and one retailer. To address the uncertain cost information, we propose a decision rule based on confidence levels to measure the goals of the supply chain participants. We provide the new concept of the belief‐degree cost of a supply chain that embodies the decision maker's ability to comprehensively address information uncertainty and control the risk caused by information uncertainty. We find that regardless of which of the three games it is in – integrated, hybrid, or decentralized – a chain should order more and thereby gain more profit when its cost uncertainty increases or the competing chain's cost uncertainty decreases. The chain with a low or sufficiently low belief‐degree cost gains a competitive advantage on both quantity and profit. A chain's competitiveness can be enhanced by either decreasing its confidence level or increasing its rival's confidence level. Furthermore, we demonstrate that supply chain integration is the dominant strategy for given confidence levels. Nevertheless, a prisoner's dilemma occurs when the differences in the belief‐degree costs of the two supply chains are not significant and the competitive intensity is high. In addition, the magnitudes of the confidence levels can be changed to avoid or cause a prisoner's dilemma. Finally, under different confidence levels, the Stackelberg model for competing hybrid or decentralized supply chains is extended to the bargaining model, and the impact of bargaining power on supply chain competition is analyzed. [ABSTRACT FROM AUTHOR]

High‐performance lightweight polymer fibers are attracting significant interest for wearable systems, where its thermal insulation performance is indispensable for harsh environments. However, one drawback of polymer fibers is its limited operating temperature range. Herein, a crosslinked poly(p‐phenylene terephthalamide) fiber and ceramic aerogel nanocomposite is reported, exhibiting hot and cold thermal management from cryogenic to high‐temperature condition (over 400 °C) and robust mechanical performance, which can be produced using additive textile manufacturing. The resulting ceramic aerogel nanocomposites demonstrate a low density (0.08 g cm−3), a low thermal conductivity (0.034 W m−1 K−1), and a high compressive mechanical strength of 1.1 MPa, due to the crosslinked interfacial interaction between the aramid fiber and the silica aerogel. A finite‐element model is developed to study the compression performance of aramid–aerogel composite, demonstrating that the robust mechanical performance is strengthened by interfacial bonding. These findings demonstrate that composite sheets are promising candidates for the low‐cost manufacturing of wearable textiles for applications in harsh environments. [ABSTRACT FROM AUTHOR]

A fundamental understanding of the remarkable impact of water on the interfacial processes of lithium–oxygen (Li–O2) reactions is of great significance for the practical application of Li–O2 batteries. However, clarifying the growth pathway and surface dynamics of active products regulated by water at the nanoscale is still at a preliminary stage. Here, the interfacial evolution of cathode processes mediated by water in Li–O2 batteries is successfully revealed by using in situ atomic force microscopy. Under the regulation of additive water, the morphology of discharge product Li2O2 is changed from a toroidal shape to a lamellar one with water content increasing, by contrast, the latter one shows a lower decomposition potential with faster dynamics upon charging. Moreover, real‐time visualization directly shows that inducing water into the DMSO‐based electrolyte can switch the pathway of Li2O2 nucleation from a surface‐mediated mechanism to solution‐mediated mechanism, which in turn affects product distribution and battery performance. Furthermore, it is found that the applied current density and additive water can antagonistically impact the interfacial behavior. The insights into the effect of water on the nucleation modes and evolution processes of Li2O2 provides a deeper understanding of the interfacial reactions in Li–O2 batteries. [ABSTRACT FROM AUTHOR]

Osteolytic diseases are typified by over‐enhanced formation and resorbing function of osteoclasts and have a major impact on human health. Inhibition of osteoclastic differentiation and function is a key strategy for clinical therapy of osteolytic conditions. Maackiain is a natural compound extracted from Sophora flavescens, which has been applied to anti‐allergic and anti‐tumour treatments. The present results showed that Maackiain could restrain receptor activator of nuclear factor‐κB ligand (RANKL)‐stimulated osteoclast formation and hydroxyapatite resorption dose‐dependently, and interrupt the structures of F‐actin belts in the mature osteoclasts. It also repressed the expressions of osteoclast‐specific genes and proteins. Furthermore, Maackiain could inhibit RANKL‐stimulated NF‐κB and calcium signalling pathways, and dampen Nuclear factor of activated T cell cytoplasmic 1 activity, protein expression and translocation into the nucleus. These results revealed that Maackiain may have a potential therapeutic effect on osteoclast‐related disorders. [ABSTRACT FROM AUTHOR]

Osteolytic skeletal disorders are caused by an imbalance in the osteoclast and osteoblast function. Suppressing the differentiation and resorptive function of osteoclast is a key strategy for treating osteolytic diseases. Dracorhodin perchlorate (D.P), an active component from dragon blood resin, has been used for facilitating wound healing and anti‐cancer treatments. In this study, we determined the effect of D.P on osteoclast differentiation and function. We have found that D.P inhibited RANKL‐induced osteoclast formation and resorbed pits of hydroxyapatite‐coated plate in a dose‐dependent manner. D.P also disrupted the formation of intact actin‐rich podosome structures in mature osteoclasts and inhibited osteoclast‐specific gene and protein expressions. Further, D.P was able to suppress RANKL‐activated JNK, NF‐κB and Ca2+ signalling pathways and reduces the expression level of NFATc1 as well as the nucleus translocation of NFATc1. Overall, these results indicated a potential therapeutic effect of D.P on osteoclast‐related conditions. [ABSTRACT FROM AUTHOR]

The Tiaopi Huxin recipe (TPHXR) is widely used in traditional Chinese medicine for the clinical treatment of coronary heart disease. However, the mechanism of TPHXR treatment of atherosclerosis (AS) has not been fully elucidated. In this study, we have aimed to explore the potential antiatherosclerotic effect of TPHXR and its underlying mechanisms. Male ApoE knockout (ApoE−/−) mice were fed a high‐fat diet for 12 weeks and were randomly divided into four groups: the control group, and the low‐dose, medium‐dose, and high‐dose TPHXR groups. The nitric oxide (NO) levels in arterial tissue and human umbilical vein endothelial cells (HUVECs) were measured by diaminofluorescein‐2 diacetate staining. Vasorelaxation of mice aorta was performed by wire myograph. Inflammatory cytokines, including tumor necrosis factor‐α (TNF‐α), hs‐CRP, IL‐6, and IL‐1β, in mice plasma were analyzed by enzyme‐linked immunosorbent assay. Western blot analysis was applied to observe protein expression. Oil Red O staining was utilized for the quantification of atherosclerotic plaques. Results showed that 4 weeks of high‐ and medium‐dose TPHXR treatment by oral gavage reduced atheromatous lesions in ApoE −/− mice. The high‐ and medium‐dose TPHXR treatment, but not the low‐dose treatment, promoted eNOS phosphorylation, increased NO levels and improved endothelium‐dependent vasorelaxation in ApoE −/− mice. High‐ and medium‐dose TPHXR, but not low‐dose TPHXR, decreased the expression of cav‐1, NF‐κB p50, NF‐κB p65, ICAM1, VCAM‐1, TNF‐α, IL‐6, and IL‐1β in the vasculature of ApoE −/− mice. Enzyme‐linked immunosorbent assay analysis indicated that high‐ and medium‐dose TPHXR decreased the levels of TNF‐α, IL‐6, hs‐CRP, and IL‐1β. In conclusion, our findings show that TPHXR improved the endothelial function and reduced atheromatous lesions in ApoE −/− mice. This result may be due to the decreased expression of caveolin‐1 and NF‐κB and, hence, the attenuated inflammatory response in AS mice vasculature. TPHXR may represent a promising intervention in patients with AS. [ABSTRACT FROM AUTHOR]

Osteoporosis is a form of osteolytic disease caused by an imbalance in bone homeostasis, with reductions in osteoblast bone formation, and augmented osteoclast formation and resorption resulting in reduced bone mass. Cajaninstilbene acid (CSA) is a natural compound derived from pigeon pea leaves. CSA possesses beneficial properties as an anti‐inflammatory, antibacterial, antihepatitis, and anticancer agent; however, its potential to modulate bone homeostasis and osteoporosis has not been studied. We observed that CSA has the ability to suppress RANKL‐mediated osteoclastogenesis, osteoclast marker gene expression, and bone resorption in a dose‐dependent manner. Mechanistically, it was revealed that CSA attenuates RANKL‐activated NF‐κB and nuclear factor of activated T‐cell pathways and inhibited phosphorylation of key signaling mediators c‐Fos, V‐ATPase‐d2, and ERK. Moreover, in osteoclasts, CSA blocked RANKL‐induced ROS activity as well as calcium oscillations. We further evaluated the therapeutic effect of CSA in a preclinical mouse model and showed that in vivo treatment of ovariectomized C57BL/6 mice with CSA protects the mice from osteoporotic bone loss. Thus, this study demonstrates that osteolytic bone diseases can potentially be treated by CSA. Cajaninstilbene acid (CSA), a natural compound derived from pigeon pea leaves, has the ability to suppress RANKL‐mediated osteoclastogenesis, osteoclast marker gene expression, and bone resorption in a dose‐dependent manner. It attenuates RANKL‐activated NF‐κB and nuclear factor of activated T‐cell (NFAT) pathways and inhibited phosphorylation of key signaling mediators c‐Fos, V‐ATPase‐d2, and ERK. Moreover, in osteoclasts, CSA blocked the RANKL‐induced ROS activity as well as calcium oscillations.The treatment of ovariectomized C57BL/6 mice with CSA protects the mice from osteoporotic bone loss. Thus, this study demonstrates that osteolytic bone diseases can potentially be treated by CSA. [ABSTRACT FROM AUTHOR]

Background: Cardiac hypertrophy and heart failure are characterized by increased late sodium current and abnormal Ca2+ handling. Ranolazine, a selective inhibitor of the late sodium current, can reduce sodium accumulation and Ca 2+ overload. In this study, we investigated the effects of ranolazine on pressure overload‐induced cardiac hypertrophy and heart failure in mice. Methods and Results: Inhibition of late sodium current with the selective inhibitor ranolazine suppressed cardiac hypertrophy and fibrosis and improved heart function assessed by echocardiography, hemodynamics, and histological analysis in mice exposed to chronic pressure overload induced by transverse aortic constriction (TAC). Ca2+ imaging of ventricular myocytes from TAC mice revealed both abnormal SR Ca 2+ release and increased SR Ca 2+ leak. Ranolazine restored aberrant SR Ca 2+ handling induced by pressure overload. Ranolazine also suppressed Na + overload induced in the failing heart, and restored Na +‐induced Ca 2+ overload in an sodium‐calcium exchanger (NCX)‐dependent manner. Ranolazine suppressed the Ca 2+‐dependent calmodulin (CaM)/CaMKII/myocyte enhancer factor‐2 (MEF2) and CaM/CaMKII/calcineurin/nuclear factor of activated T‐cells (NFAT) hypertrophy signaling pathways triggered by pressure overload. Pressure overload also prolonged endoplasmic reticulum (ER) stress leading to ER‐initiated apoptosis, while inhibition of late sodium current or NCX relieved ER stress and ER‐initiated cardiomyocyte apoptosis. Conclusions: Our study demonstrates that inhibition of late sodium current with ranolazine improves pressure overload‐induced cardiac hypertrophy and systolic and diastolic function by restoring Na+ and Ca 2+ handling, inhibiting the downstream hypertrophic pathways and ER stress. Inhibition of late sodium current may provide a new treatment strategy for cardiac hypertrophy and heart failure. In this study, we revealed the effect of ranolazine to attenuate pressure overload‐induced cardiac hypertrophy and heart failure in mice by reducing Na+ accumulation and Ca 2+ overload, normalizing SR leak. The Ca 2+‐dependent Ca 2+/calmodulin (CaM)/CaMKII/MEF2D and CaM/CaMKII/calcineurin/nuclear factor of activated T‐cells hypertrophic pathways and endoplasmic reticulum (ER) stress were triggered by pressure overload and were inhibited by ranolazine. [ABSTRACT FROM AUTHOR]

During pregnancy, a tremendous increase in fetoplacental angiogenesis is associated with elevated blood flow. Aberrant fetoplacental vascular function may lead to pregnancy complications including pre‐eclampsia. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are crucial regulators of fetoplacental endothelial function. G protein α subunit 14 (GNA14), a member of Gαq/11 subfamily is involved in mediating hypertensive diseases and tumor vascularization. However, little is known about roles of GNA14 in mediating the FGF2‐ and VEGFA‐induced fetoplacental endothelial function. Using human umbilical vein endothelial cells (HUVECs) cultured under physiological chronic low oxygen (3% O2) as a cell model, we show that transfecting cells with adenovirus carrying GNA14 complementary DNA (cDNA; Ad‐GNA14) increases (p < 0.05) protein expression of GNA14. GNA14 overexpression blocks (p < 0.05) FGF2‐stimulated endothelial migration, whereas it enhances (p < 0.05) endothelial monolayer integrity (maximum increase of ~35% over the control at 24 hr) in response to FGF2. In contrast, GNA14 overexpression does not significantly alter VEGFA‐stimulated cell migration, VEGFA‐weakened cell monolayer integrity, and intracellular Ca++ mobilization in response to adenosine triphosphate (ATP), FGF2, and VEGFA. GNA14 overexpression does not alter either FGF2‐ or VEGFA‐induced phosphorylation of ERK1/2. However, GNA14 overexpression time‐dependently elevates (p < 0.05) phosphorylation of phospholipase C‐β3 (PLCβ3) at S1105 in response to FGF2, but not VEGFA. These data suggest that GNA14 distinctively mediates fetoplacental endothelial cell migration and permeability in response to FGF2 and VEGFA, possibly in part by altering activation of PLCβ3 under physiological chronic low oxygen. Overexpression of G protein α subunit 14 (GNA14), a member of Gαq/11 subfamily has been implicated to play a role in several hypertensive disorders. However, little is known about roles of GNA14 in mediating placental endothelial function. Herein, we show GNA14 overexpression dysregulate FGF2‐stimulated placental endothelial function, possibly in part by altering activation of PLCβ3. [ABSTRACT FROM AUTHOR]

Background: Chronic drinking leads to myocardial contractile dysfunction and dilated cardiomyopathy, and cardiac fibrosis is a consequence of these alcoholic injuries. Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) to less bioactive diols, and EETs have cardioprotective properties. However, the effects of sEH inhibition in ethanol (EtOH)‐induced cardiac fibrosis are unknown. Methods: This study was designed to investigate the role and underlying mechanisms of sEH inhibition in chronic EtOH feeding‐induced cardiac fibrosis. C57BL/6J mice were fed a 4% Lieber‐DeCarli EtOH diet for 8 weeks, and the sEH inhibitor 1‐trifluoromethoxyphenyl‐3‐(1‐propionylpiperidin‐4‐yl) urea (TPPU) was administered throughout the experimental period. Results: The results showed that chronic EtOH intake led to cardiac dilatation, collagen deposition, and autophagosome accumulation, while TPPU administration ameliorated these effects. In vitro, treating primary cardiac fibroblasts (CFs) with EtOH resulted in CF activation, including alpha smooth muscle actin overexpression, collagen synthesis, and cell migration. Moreover, EtOH disturbed CF autophagic flux, as evidenced by the increased LC3 II/I ratio and SQSTM1 expression, and by the enhanced autophagosome accumulation. TPPU treatment prevented the activation of CF induced by EtOH and restored the impaired autophagic flux by suppressing mTOR activation. Conclusions: Taken together, these findings suggest that sEH pharmacological inhibition may be a unique therapeutic strategy for treating EtOH‐induced cardiac fibrosis. [ABSTRACT FROM AUTHOR]

Key points: Fetoplacental vascular growth is critical to fetal growth. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are two major regulators of fetoplacental vascular growth. G protein α subunit 11 (GNA11) transmits signals from many external stimuli to the cellular interior and may mediate endothelial function. It is not known whether GNA11 mediates FGF2‐ and VEGFA‐induced endothelial cell responses under physiological chronic low O2. In the present study, we show that knockdown of GNA11 significantly decreases FGF2‐ and VEGFA‐induced fetoplacental endothelial cell migration but not proliferation and permeability. Such decreases in endothelial migration are associated with increased phosphorylation of phospholipase C‐β3. The results of the present study suggest differential roles of GNA11 with respect to mediating FGF2‐ and VEGFA‐induced fetoplacental endothelial function. Abstract: During pregnancy, fetoplacental angiogenesis is dramatically increased in association with rapidly elevated blood flow. Any disruption of fetoplacental angiogenesis may lead to pregnancy complications such as intrauterine growth restriction. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are crucial regulators of fetoplacental angiogenesis. G protein α subunits q (GNAq) and 11 (GNA11) are two members of the Gαq/11 subfamily involved in mediating vascular growth and basal blood pressure. However, little is known about the roles of GNA11 alone with respect to mediating the FGF2‐ and VEGFA‐induced fetoplacental endothelial function. Using a cell model of human umbilical cord vein endothelial cells cultured under physiological chronic low O2 (3% O2), we showed that GNA11 small interfering RNA (siRNA) dramatically inhibited (P < 0.05) FGF2‐ and VEGFA‐stimulated fetoplacental endothelial migration (by ∼36% and ∼50%, respectively) but not proliferation and permeability. GNA11 siRNA also elevated (P < 0.05) FGF2‐ and VEGFA‐induced phosphorylation of phospholipase C‐β3 (PLCβ3) at S537 in a time‐dependent fashion but not mitogen‐activated protein kinase 3/1 (ERK1/2) and v‐akt murine thymoma viral oncogene homologue 1 (AKT1). These data suggest that GNA11 mediates FGF2‐ and VEGFA‐stimulated fetoplacental endothelial cell migration partially via altering the activation of PLCβ3. [ABSTRACT FROM AUTHOR]

Segmental polyurethanes (PU) with hydrophilic segments form colloidal dispersions which are ultimately arrested into gel-like structure in aqueous continuous phase owing to the differential interactions between polymer and solvent. These structural states of amphiphilic PUs evolve hierarchically, but the structure-function correlation between PU colloidal dispersion and gels is not clear. Here, this correlation is defined from the mechanomorphology of hydrophilic polyethylene glycol based PU which forms dispersions and finally transforms into gel-structure. Morphological and rheological analyses show that PU with comparable hydrophilic and hydrophobic content forms attractive colloids with self-similar fractal microstructures whereas PU with increased hydrophilic character forms space-filling colloids without any defined organization. Furthermore, colloidal dispersions are densified under shear or gravity to form gel where gel mechanics is defined by colloidal particle organization and the morphology is dependent on gelation mode. This stepwise organization of PU colloidal particles into microgel can independently control microgel mechanics and morphology. [ABSTRACT FROM AUTHOR]

An Radio-Frequency (RF) Inductively Coupled Plasma (ICP) ion source test facility has been successfully developed at Huazhong University of Science and Technology (HUST). As part of a study on hydrogen plasma, the influence of three main operation parameters on the RF power necessary to ignite plasma was investigated. At 6 Pa, the RF power necessary to ignite plasma influenced little by the filament heating current from 5 A to 9 A. The RF power necessary to ignite plasma increased rapidly with the operation pressure decreasing from 8 Pa to 4 Pa. The RF power necessary to ignite plasma decreased with the number of coil turns from 6 to 10. During the experiments, plasma was produced with the electron density of the order of 1016m-3 and the electron temperature of around 4 eV. (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

SUMMARY: Cooperative game theory can be applied to orthogonal frequency division multiple access (OFDMA) networks for fair resource allocation. In this work, we consider a comprehensive cross‐layer framework including physical and medium access control layer requirements. We apply two cooperative games, nontransferable utility (NTU) game and transferable utility (TU) game, to provide fairness in OFDMA networks. In NTU game, fairness is achieved by defining appropriate objective function, whereas in TU game, fairness is provided by forming the appropriate network structure. For NTU game, we analyze the Nash bargaining solution as a solution of NTU game taking into account channel state information and queue state information. In a TU game, we show that coalition among subcarriers to jointly provide rate requirements leads to better performance in terms of power consumption. The subcarrier's payoff is determined according to the amount of payoff which that subcarrier brings to the coalition by its participation. We show that although NTU and TU games are modeled as rate adaptive and margin adaptive problems, respectively, both solutions provide a fair distribution of resources with minimum fairness index of 0.8. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

With the increase of using aluminum alloys and high strength steels to replace traditional steels, precise prediction of sheet springback and corresponding compensation methods become more and more important for die design because these material' s higher ratio of yield strength to elastic modulus causes more serious springback problems. In this paper, a semi-analytic springback prediction and compensation model based on in-process measurement is proposed. For springback prediction, measured strain and curvature data from the actual stamping process are incorporated in a semi-analytic model, and then springback is predicted based on the elastic unloading from the residual differential stress during sheet metal forming. In the next stage of die design, a procedure to automatically compensate the tool geometry, including the fundamental mechanics analysis and the reconstruction of the tool surface, is presented. For validation purpose, a case study was carried out for the tool optimization of a double curved panel. [ABSTRACT FROM AUTHOR]

SUMMARY To apply a beamforming algorithm with a linear array of N antennas in real wireless communication systems, two main issues should be addressed: Algorithm complexity and number of antennas. In this paper, we propose three simple beamforming algorithms for direct sequence code division multiple access systems. We first propose a new framework to obtain the updating equation for the weight vector using PCA. Then, using this framework, four different objective functions are used as examples to illustrate how to obtain new adaptive algorithms. We demonstrate that these objective functions lead to three novel blind algorithms, with two of them resulting in the same algorithm. Moreover, they have considerably low complexities, requiring only 2 N-1 complex additions and either 2 N+1 or 2 N complex multiplications for a single run. We evaluate the performances of these algorithms in estimating the angle-of-arrival of the desired signal and in producing the array beam pattern, and in alleviating the BER in Rayleigh fading and AWGN channels. In summary, these new beamforming algorithms obtained based on the proposed framework operate as blind algorithms, have low computational complexities, and offer desirable performances even if N is restricted.Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Part shape error due to springback is a manufacturing defect in the sheet metal forming. This problem can be corrected by adjusting the tool shape to an appropriate shape or process optimization. In this paper, a discrete curvature adjustment (DCA) strategy is developed for tool design of channel bending products. This strategy aims at generating the right tool shape in a short time using the measured data from the trial part. A dynamic compensation factor which varies with part geometry and specific process condition will also be used to adjust the tool curvatures. Applications of this method in the tool design of an asymmetrical U-shaped part, an industrial blade, and a cylindrical part were presented. The experiment results demonstrated that this strategy was able to reduce the trial times of die modification from five or six to one or two, thus saving time and cost in the industry production. Additionally, the comparison of this method with the existing displacement adjustment (DA) method was also discussed. [ABSTRACT FROM AUTHOR]