Diagnostic value of serum CRP, PCT and IL-6 in children with nephrotic syndrome complicated by infection: a single center retrospective study.

OBJECTIVE: The purpose was to look into the diagnostic value of serum CRP, PCT and IL-6 in children with nephrotic syndrome co-infection. METHODS: One hundred and forty-nine children with nephrotic syndrome who met the inclusion and exclusion criteria were included in this study. The children were divided into three groups: bacterial infection group, non-bacterial infection group, and non-infection group. The diagnostic value was analyzed and compared using the ROC curve. RESULTS: There was no statistically significant difference in the Leukocyte counts among three groups. The mean results of serum CRP, PCT and IL-6 were significantly higher in the bacterial infection group compared to those in the non-infection group (p < 0.05). AUC of CRP, PCT, IL-6 in bacterial infection were 0.791, 0.859, 0.783. The following combinations CRP + PCT + IL-6, IL-6 + PCT, CRP + PCT significantly increased the efficiency of bacterial infection diagnosis, the AUCs were 0.881, 0.884, and 0.884, respectively. AUC of PCT in non-bacterial infection was 0.663. The combinations of these three clinical indicators performed no better than PCT in ROC analysis. CONCLUSION: Normal CRP or IL-6 levels do not rule out the diagnosis of bacterial infection in children on long-term glucocorticoid therapy. The appropriate combination of two or three indicators can improve the diagnostic value. IMPACT: This study evaluated the diagnostic value of the serum concentrations of CRP, PCT and IL-6 and assessed whether the value of their combined application is better than when used alone for diagnosing primary nephrotic syndrome complicated by infection. The elevation in leukocyte count cannot be used to diagnose children with nephrotic syndromes on long-term glucocorticoid treatment who have bacterial infections. Normal CRP or IL-6 levels do not rule out the diagnosis of bacterial infection in children on long-term glucocorticoid therapy. The appropriate combination of two or three indicators can improve diagnostic value, sensitivity, and specificity.

External validation of the pediatric International IgA Nephropathy Prediction Tool in a central China cohort.

BACKGROUND: This study aimed to externally validate the pediatric International IgA Nephropathy (IgAN) Prediction Tool updated from the adult IgAN Prediction Tool. METHODS: 439 children with biopsy-confirmed idiopathic IgAN were enrolled in this external validation study. The primary outcome was a 30% decline in eGFR or end-stage kidney disease. We evaluated the discrimination using Harrell's C-index, the receiver operating characteristic (ROC) curve, and Kaplan-Meier curves for four risk groups (< 16th [low risk], ∼16 to < 50th [intermediate risk], ∼50 to < 84th [high risk], and ≥ 84th percentiles [highest risk] of linear predictor). Calibration was assessed using calibration plots. RESULTS: The median follow-up time of the 439 patients was 4.5 (2.7-6.8) years, and 27 patients reached the primary outcome. Compared with the reported cohorts, our cohort was more contemporary, with milder proteinuria at biopsy, and had lower proportions of S1 and T1 lesions. Harrell's C-index and area under the ROC curve at 5 years were < 0.7 for both the models with and without race. The Kaplan-Meier curves of the risk groups were not well separated for the two models, only separated completely between the highest-risk group and the others for the model without race. The two models generally overestimated the risk of the primary outcome, CONCLUSION: The model without race could accurately distinguish the highest-risk patients from patients with low, intermediate, and high risk for kidney progression. Discrimination and calibration for the full model with or without race were unsatisfactory in this contemporary cohort in central China.

The A-to-I editing of KPC1 promotes intrahepatic cholangiocarcinoma by attenuating proteasomal processing of NF-κB1 p105 to p50.

BACKGROUND: Aberrant RNA editing of adenosine-to-inosine (A-to-I) has been linked to multiple human cancers, but its role in intrahepatic cholangiocarcinoma (iCCA) remains unknown. We conducted an exome-wide investigation to search for dysregulated RNA editing that drive iCCA pathogenesis. METHODS: An integrative whole-exome and transcriptome sequencing analysis was performed to elucidate the RNA editing landscape in iCCAs. Putative RNA editing sites were validated by Sanger sequencing. In vitro and in vivo experiments were used to assess the effects of an exemplary target gene Kip1 ubiquitination-promoting complex 1 (KPC1) and its editing on iCCA cells growth and metastasis. Crosstalk between KPC1 RNA editing and NF-κB signaling was analyzed by molecular methods. RESULTS: Through integrative omics analyses, we revealed an adenosine deaminases acting on RNA 1A (ADAR1)-mediated over-editing pattern in iCCAs. ADAR1 is frequently amplified and overexpressed in iCCAs and plays oncogenic roles. Notably, we identified a novel ADAR1-mediated A-to-I editing of KPC1 transcript, which results in substitution of methionine with valine at residue 8 (p.M8V). KPC1 p.M8V editing confers loss-of-function phenotypes through blunting the tumor-suppressive role of wild-type KPC1. Mechanistically, KPC1 p.M8V weakens the affinity of KPC1 to its substrate NF-κB1 p105, thereby reducing the ubiquitinating and proteasomal processing of p105 to p50, which in turn enhances the activity of oncogenic NF-κB signaling. CONCLUSIONS: Our findings established that amplification-driven ADAR1 overexpression results in overediting of KPC1 p.M8V in iCCAs, leading to progression via activation of the NF-κB signaling pathway, and suggested ADAR1-KPC1-NF-κB axis as a potential therapeutic target for iCCA.

SPP1 is a prognostic related biomarker and correlated with tumor-infiltrating immune cells in ovarian cancer.

BACKGROUND: Secreted phosphoprotein 1 (SPP1) plays a vital role in tumor progression of multiple cancer types However, it still awaits further exploration whether SPP1 is a bystander or an actual player in the modulation of immune infiltration in ovarian cancer. METHODS: In this study, the expression level of SPP1 was identified by Oncomine, GEPIA and TIMER databases, and the result of SPP1 immumohistochemical staining was acquired by The HPA database. The impact of SPP1 expression level on the clinical outcome of ovarian cancer patients were evaluated via Kaplan-Meier Plotter and PrognoScan dataset. Immune infiltration analyses were conducted using TIMER and TISIDB dataset. In addition, Functional enrichment analyses were performed with Metascape and GeneMANIA database. To verify these findings from the public database, the results were validated in a cohort of ovarian cancer patients. RESULTS: SPP1 was found to be overexpressed in ovarian tumor tissues and high SPP1 expression was correlated with shorter survivals. Notably, SPP1 expression was positively correlated with infiltrating levels of CD4 + T cells, CD8 + T cells, macrophages, neutrophils, and dendritic cells. Furthermore, SPP1 expression level showed strong correlation with diverse immune cells in ovarian cancer. Of note, functional enrichment analysis suggested that SPP1 was strongly correlated with immune response. CONCLUSIONS: These findings imply that SPP1 is correlated with prognosis and immune cell infiltrating, offering a new potential immunotherapeutic target in ovarian cancer. TRIAL REGISTRATION: Not applicable.

Management and prognosis comparison between incidental and nonincidental intravenous leiomyomatosis: a retrospective single-center real-life experience.

Background: Intravenous leiomyomatosis (IVL) is a rare, difficult-to-treat type of smooth muscle tumor that originates from the uterine myoma. However, its clinical characteristics, management, and prognosis are not clearly understood. Moreover, the 2 different methods used to diagnose IVL-incidental and nonincidental-result in completely different treatments. Methods: We conducted a single-center, retrospective study. Our real-life case series included patients pathologically diagnosed with IVL between July 2011 and December 2020. All patients with IVL were divided into 2 groups: an incidental group and a nonincidental group. Medical records of patients, including clinical characteristics, primary treatment, treatment after recurrence, and prognosis, were reviewed. Results: A total of 39 patients were included in the study, with a median patient age of 47 years. Of the 39 cases, 15 (38.5%) were incidentally diagnosed with only intrapelvic tumors. Among the 24 patients with IVL in the nonincidental group, tumor spread in the inferior vena cava, right heart, and pulmonary artery was identified in 4, 17, and 3 patients, respectively. The most common symptoms were abnormal uterine bleeding in the incidental group and chest distress and dyspnea in the nonincidental group. Among the 15 patients in the incidental group, ovary-preserving surgery was performed in 6 young women (≤40 years old), of whom 3 underwent myomectomy. All 24 patients with IVL in the nonincidental group underwent thrombectomy without uterine or ovary preservation by multidisciplinary surgical treatment. Only 1 patient in each group underwent postoperative adjuvant therapy. During the median follow-up of 36.0 months, recurrence was recorded in 5 (12.8%) cases in the incidental group, with no deaths recorded. Only 1 patient was lost to follow-up. No recurrence was noted in the cases in the nonincidental group. Among the 5 patients who experienced recurrence, 4 received secondary surgical treatment and 1 received hormone therapy. All patients were alive as of this report. Conclusions: Patients with IVL who are diagnosed incidentally have a higher recurrence risk than those who are diagnosed nonincidentally and undergo complete tumor resection. However, patients incidentally diagnosed with IVL can still experience long disease-free survival rates following secondary surgical treatment after recurrence.

A Wide-Range Stiffness-Tunable Soft Actuator Inspired by Deep-Sea Glass Sponges.

Achieving both high compliance and stiffness is a key issue in stiffness-tunable soft robots. A wide-range variable-stiffness method keeping pure soft characteristic is proposed by bioinspired design of deep-sea glass sponges adopting thermoplastic starch. The stiffness-tunable mechanism is designed through force analysis and optimization of its bionic cellular structure. It is fabricated with load-weight ratio exceeding 470. Then, a wide-range stiffness-tunable omnidirectional-bending soft actuator (WOSA) is realized, and the bending stiffness model is established. Comparative experiments of stiffness and deformation are conducted on WOSA and a pure soft actuator (PSA) with the same size. Results show that the WOSA can get 92.3 times initial bending and 70.8 times torsional stiffness variation range, of which the flexibility is even better than PSA. A gripper assembled by three WOSAs is verified through stiffness adjustment that it can grasp different weight fragile, soft items from the unshelled fresh egg, boiled egg yolk to grapes. It can even lift a dumbbell weighting 3.32 kg. Finally, a manipulator demonstrated its potential in future minimally invasive surgical applications due to its wide stiffness range and large deformation capacity.

pH and charge reversal-driven nanoplatform for efficient delivery of therapeutics.

Nanomedicine which delivers therapeutics to tumours holds great potential for cancer treatment. However, endosomal trapping and uncontrollable release usually limit the efficiency of nanomedicine. Herein, a smart mesoporous silica based nanoplatform was constructed, in which mesoporous silica nanoparticles (MSNs) serve as the core, capped with pH-induced charge-reversal polymer -PAH-cit- and cationic polyelectrolyte polyethyleneimine (PEI). The oppositely charged polymer can not only act as a gatekeeper for controlled release, but also mediated efficient endosomal escape of the therapeutics. Under the acidic endosomal environment, the hydrolysis of acid-cleavable bonds in PAH-Cit would trigger the charge reversal and endosomal escape of the nanoplatform for efficient drug release. Furthermore, the prepared nanoplatform demonstrated a higher tumor cell proliferation inhibition rate than free theruputics in vitro assays and significantly inhibited tumour growth in the 4T1 tumour model in mice. Therefore, our strategy offers a simple and general nanoplatform to delivery therapeutics to tumours with efficient endosomal escape and controlled release.

Primary Laparoscopic Surgery Does Not Affect the Prognosis of Early-Stage Ovarian Clear Cell Cancer.

PURPOSE: Minimally invasive surgery (MIS) is performed frequently in early-stage ovarian cancer patients, especially in ovarian clear cell carcinoma (OCCC). The aim of this study was to investigate whether primary laparoscopic surgery influences prognosis in patients with early-stage OCCC. PATIENTS AND METHODS: Patients with International Federation of Gynecology and Obstetrics (FIGO) stage I  OCCC were retrospectively reviewed in two hospitals between April 2010 and August 2020. Clinical data were abstracted, and patients were followed up until February 2021. Patients were divided into open surgery (laparotomy) and laparoscopy groups, and the Kaplan-Meier method was applied to compare progression-free survival (PFS) and overall survival (OS) between the groups. Statistical differences were determined by the Log rank test. RESULTS: Eighty-nine patients were included in the study; 20 (22.5%) and 69 (77.5%) patients underwent laparoscopic and open surgery, respectively. The patients' characteristics were well-balanced except that patients in the laparoscopy group tended to have smaller tumors and lower frequency of omentectomy and lymphadenectomy compared with the open surgery group. The median follow-up duration was 42.6 and 36.5 months in the laparoscopy and open surgery groups, respectively. Nine (10.1%) patients developed recurrence, and 4 (4.5%) died of the disease; all in the open surgery group. The estimated 2-year PFS rates were 100.0% and 90.1%, and the estimated 5-year OS rates were 100.0% and 91.9% in the laparoscopy and open surgery groups, respectively. No significant survival differences were found between the groups. CONCLUSION: Survival was not compromised when primary laparoscopic surgery was performed in early-stage OCCC patients. A well-designed randomized controlled trial is warranted.

Therapeutic Role of Retroperitoneal Lymphadenectomy in 170 Patients With Ovarian Clear Cell Cancer.

INTRODUCTION: We evaluated the therapeutic role of retroperitoneal lymphadenectomy in patients with ovarian clear cell cancer (OCCC). MATERIALS AND METHODS: We retrospectively reviewed 170 OCCC patients diagnosed at two hospitals in China between April 2010 and August 2020. Clinical data were abstracted, and patients were followed until February 2021. Patients were divided into retroperitoneal lymphadenectomy and no lymphadenectomy groups. The Kaplan-Meier method was used to compare progression-free (PFS) and overall survival (OS) between the two groups. Statistical differences were determined by the log-rank test. The COX proportional hazards regression model was applied to identify predictors of tumor recurrence. RESULTS: The median age was 52 years; 90 (52.9%) and 80 (47.1%) patients were diagnosed as early and advanced stage, respectively. Clinically positive and negative nodes was found in 40 (23.5%) and 119 (70.0%) patients, respectively. Of all the 170 patients, 124 (72.9%) patients underwent retroperitoneal lymphadenectomy, while 46 (27.1%) did not. The estimated 2-year PFS and 5-year OS rates were 71.4% and 65.9% in the lymphadenectomy group, and 72.0% and 73.7% in no lymphadenectomy group (p = 0.566 and 0.669, respectively). There was also no difference in survival between the two groups when subgroup analysis was performed stratified by early and advanced stage, or in patients with clinically negative nodes. Multivariate analysis showed that retroperitoneal lymphadenectomy were not an independent predictor of tumor recurrence. CONCLUSION: Retroperitoneal lymphadenectomy provided no survival benefit in patients diagnosed with OCCC. A prospective clinical trial is needed to confirm the present results.

LncRNA PVT1 Suppresses the Progression of Renal Fibrosis via Inactivation of TGF-ß Signaling Pathway.

BACKGROUND: Renal fibrosis is a frequent pathway leading to end-stage kidney dysfunction. In addition, renal fibrosis is the ultimate manifestation of chronic kidney diseases (CKD). Long noncoding RNAs (lncRNAs) are known to be involved in occurrence of renal fibrosis, and lncRNA plasmacytoma variant translocation 1 (PVT1) has been reported to act as a key biomarker in renal diseases. However, the role of PVT1 in renal fibrosis remains unclear. MATERIALS AND METHODS: HK-2 cells were treated with TGF-ß1 to mimic renal fibrosis in vitro. Gene and protein expressions in HK-2 cells were measured by qRT-PCR and Western-blot, respectively. ELISA was used to test the level of creatinine (CR) and blood urea nitrogen (BUN) in serum of mice. Additionally, unilateral ureteral obstruction (UUO)-induced renal fibrosis mice model was established to investigate the effect of PVT1 on renal fibrosis in vivo. RESULTS: PVT1 was upregulated in TGF-ß1-treated HK-2 cells. In addition, TGF-ß1-induced upregulation of α-SMA and fibronectin in HK-2 cells was significantly reversed by PVT1 knockdown. Meanwhile, PVT1 bound to miR-181a-5p in HK-2 cells. Moreover, miR-181a-5p directly targeted TGF-ßR1. Furthermore, miR-181a-5p antagonist could significantly reverse the anti-fibrotic effect of PVT1 knockdown. Besides, knockdown of PVT1 notably attenuated the symptom of renal fibrosis in vivo. CONCLUSION: Knockdown of PVT1 significantly inhibited the progression of renal fibrosis in vitro and in vivo. Thus, PVT1 may serve as a potential target for the treatment of renal fibrosis.

MiR-485-5p Promotes Neuron Survival through Mediating Rac1/Notch2 Signaling Pathway after Cerebral Ischemia/Reperfusion.

OBJECTIVE: Ischemia-reperfusion (I/R) injury is a pathological feature of ischemic stroke. This study investigated the regulatory role of miR-485-5p in I/R injury. METHODS: SH-SY5Y cells were induced with oxygen and glucose deprivation/reoxygenation (OGD/R) to mimic I/R injury in vitro. Cells were transfected with designated constructs (miR-485- 5p mimics, miR-485-5p inhibitor, lentiviral vectors overexpressing Rac1 or their corresponding controls). Cell viability was evaluated using the MTT assay. The concentrations of lactate dehydrogenase, malondialdehyde, and reactive oxygen species were detected to indicate the degree of oxidative stress. Flow cytometry and caspase-3 activity assay were used for apoptosis assessment. Dual-luciferase reporter assay was performed to confirm that Rac family small GTPase 1 (Rac1) was a downstream gene of miR-485-5p. RESULTS: OGD/R resulted in decreased cell viability, elevated oxidative stress, increased apoptosis, and downregulated miR-485-5p expression in SH-SY5Y cells. MiR-485-5p upregulation alleviated I/R injury, evidenced by improved cell viability, decreased oxidative markers, and reduced apoptotic rate. OGD/R increased the levels of Rac1 and neurogenic locus notch homolog protein 2 (Notch2) signaling-related proteins in cells with normal miR-485-5p expression, whereas miR- 485-5p overexpression successfully suppressed OGD/R-induced upregulation of these proteins. Furthermore, the delivery of vectors overexpressing Rac1 in miR-485-5p mimics-transfected cells reversed the protective effect of miR-485-5p in cells with OGD/R-induced injury. CONCLUSION: This study showed that miR-485-5p protected cells following I/R injury via targeting Rac1/Notch2 signaling suggest that targeted upregulation of miR-485-5p might be a promising therapeutic option for the protection against I/R injury.

Biodegradable hybrid mesoporous silica nanoparticles for gene/chemo-synergetic therapy of breast cancer.

Mesoporous silica nanoparticles have been extensively explored in anticancer nanomedicine due to their excellent biodegradability, which is one important focus in their further clinical translations. However, the traditional design concepts based on the functional modification with active groups cannot significantly improve the controlled drug release efficiency and anticancer effect. Herein, a molecularly organic-inorganic hybrid mesoporous silica nanoparticle (HMSN) nanocarrier coated with hyaluronic acid (HA) and polyethyleneimine (PEI) was constructed for the gene/chemo-synergetic therapy of breast cancer. Notably, HMSN with tumor-sensitive disulfide bond and targeting ligand HA can be decomposed when it encounters high concentration of glutathione (GSH) and hyaluronidase (HAase). The biodegradability of host molecules and the fast disintegration of the framework in tumor microenvironment can also accelerate the stimuli responsive release of cargos inside the pore space. Furthermore, the grafting of polyethyleneimine (PEI) could increase gene loading efficiency. From the above, the smart approach involves a combination of biodegradability and biological effect and results in synergetic antitumor effect of gene and chemical drug on breast cancer. All these findings demonstrated that HMSN/HA/PEI nanocarriers can be suitable for biomedical application, paving the way to fast development of multi-functional nano-biomedicine.

Loss of NLRP3 Function Alleviates Murine Hepatic Graft-versus-Host Disease.

NLRP3 is associated with multiple risks in graft-versus-host disease, though unifying principles for these findings remain largely unknown. To explore the effects and mechanisms of the absence of NLRP3 function on hepatic graft-versus-host-disease, we established an allogeneic hematopoietic cell transplantation mice model by infusing bone marrow mononuclear cells and spleno-T cells of the BALB/c mouse into either NLRP3 knockout (NLRP3-/- ) or wild-type C57BL/6 mice. Elevated inflammatory cell infiltration, liver fibrosis, and secretions of alanine aminotransferase (ALT) and aspartate transaminase (AST), together with weight loss, were observed in C57BL/6 recipients after transplantation. However, moderate injury pathology was detected in the liver of NLRP3-/- recipients at day 14, which gradually improved over time. Likewise, proinflammatory cytokine IL-1ß, a downstream effecter of NLRP3 inflammasome activation, showed significantly lower expression (P < .05) in the liver of NLRP3-/- recipients relative to C57BL/6 recipients at day 7 and day 21. Moreover, compared with C57BL/6 recipients, the expression of both TNF-α and IL-1ß were decreased 3-fold and 4.7-fold, respectively, at day 21 in NLRP3-/- recipients. Interestingly, NLRP1a was expressed at a significantly reduced level in the liver of NLRP3-/- recipients (P < .001). Furthermore, systemic inflammation was analyzed by measuring the concentration of IL-1ß and adenosine triphosphate (ATP) in serum. The concentration of IL-1ß achieved a maximum at day 14, then decreased at day 21 and day 28 in NLRP3-/- recipients. In contrast, the concentration of IL-1ß in C57BL/6 recipients gradually increased from day 7 to day 28. ATP levels reduced from day 7 to day 28 in NLRP3-/- recipients, but were extremely high in C57BL/6 recipients from day 14 to day 28 (P < .01). The decreased levels of P2X7R were connected to less ATP in NLRP3-/- recipients at day 21 and day 28. In conclusion, NLRP3 knockout in recipients could significantly relieve liver injury after transplantation and block the NLRP3 inflammasome pathway, thus providing a promising strategy for the treatment of graft-versus-host disease prophylaxis.

Holey nickel hydroxide nanosheets for wearable solid-state fiber-supercapacitors.

Holey nickel hydroxide (Ni(OH)2) nanosheets with a mean thickness of 2 nm are facilely synthesized, and then embedded in carbon nanotube (CNT) scaffolds to construct a hybrid fiber electrode, which shows a high volumetric capacitance of 335.9 F cm-3 at 0.8 A cm-3 and superior rate performance. The hybrid supercapacitor made from the Ni(OH)2/CNT fiber can deliver a high specific capacitance of 24.8 F cm-3 and an energy density of 5.8 mW h cm-3 with outstanding mechanical stability under repeated bending conditions.

Phase 1 and pharmacokinetic study of LY3007113, a p38 MAPK inhibitor, in patients with advanced cancer.

Background The signaling protein p38 mitogen-activated protein kinase (MAPK) regulates the tumor cell microenvironment, modulating cell survival, migration, and invasion. This phase 1 study evaluated the safety of p38 MAPK inhibitor LY3007113 in patients with advanced cancer to establish a recommended phase 2 dose. Methods In part A (dose escalation), LY3007113 was administered orally every 12 h (Q12H) at doses ranging from 20 mg to 200 mg daily on a 28-day cycle until the maximum tolerated dose (MTD) was reached. In part B (dose confirmation), patients received MTD. Safety, pharmacokinetics, pharmacodynamics, and tumor response data were evaluated. Results MTD was 30 mg Q12H. The most frequent treatment-related adverse events (>10%) were tremor, rash, stomatitis, increased blood creatine phosphokinase, and fatigue. Grade ≥ 3 treatment-related adverse events included upper gastrointestinal haemorrhage and increased hepatic enzyme, both occurring at 40 mg Q12H and considered dose-limiting toxicities. LY3007113 exhibited an approximately dose-proportional increase in exposure and time-independent pharmacokinetics after repeated dosing. Maximal inhibition (80%) of primary biomarker MAPK-activated protein kinase 2 in peripheral blood mononuclear cells was not reached, and sustained minimal inhibition (60%) was not maintained for 6 h after dosing to achieve a biologically effective dose (BED). The best overall response in part B was stable disease in 3 of 27 patients. Conclusions The recommended phase 2 dosage of LY3007113 was 30 mg Q12H. Three patients continued treatment after the first radiographic assessment, and the BED was not achieved. Further clinical development of this compound is not planned as toxicity precluded achieving a biologically effective dose.

Design of a wearable and shape-memory fibriform sensor for the detection of multimodal deformation.

A wearable and shape-memory strain sensor with a coaxial configuration is designed, comprising a thermoplastic polyurethane fiber as the core support, well-aligned and interconnected carbon nanotubes (CNTs) as conductive filaments, and polypyrrole (PPy) coating as the cladding layer. In this design, the stress relaxation between CNTs is well confined by the outer PPy cladding layer, which endows the fibriform sensor with good reliability and repeatability. The microcracks generated when the coaxial fiber is under strain guarantee the superior sensitivity of this fibriform sensor with a gauge factor of 12 at 0.1% strain, a wide detectable range (from 0.1% to 50% tensile strain), and the ability to detect multimodal deformation (tension, bending, and torsion) and human motions (finger bending, breathing, and phonation). In addition, due to its shape-memory characteristic, the sensing performance of the fibriform sensor is well retained after its shape recovers from 50% deformation and the fabric woven from the shape-memory coaxial fibers can be worn on the elbow joints in a reversible manner (original-enlarged-recovered) and fitted tightly. Thus, this sensor shows promising applications in wearable electronics.

Highly Concentrated, Ultrathin Nickel Hydroxide Nanosheet Ink for Wearable Energy Storage Devices.

Solution-based techniques are considered as a promising strategy for scalable fabrication of flexible electronics owing to their low-cost and high processing speed. The key to the success of these techniques is dominated by the ink formulation of active nanomaterials. This work successfully prepares a highly concentrated two dimensional (2D) crystal ink comprised of ultrathin nickel hydroxide (Ni(OH)2 ) nanosheets with an average lateral size of 34 nm. The maximum concentration of Ni(OH)2 nanosheets in water without adding any additives reaches as high as 50 mg mL-1 , which can be printed on arbitrary substrates to form Ni(OH)2 thin films. As a proof-of-concept application, Ni(OH)2 nanosheet ink is coated on commercialized carbon fiber yarns to fabricate wearable energy storage devices. The thus-fabricated hybrid supercapacitors exhibit excellent flexibility with a capacitance retention of 96% after 5000 bending-unbending cycles, and good weavability with a high volumetric capacitance of 36.3 F cm-3 at a current density of 0.4 A cm-3 , and an energy density of 11.3 mWh cm-3 at a power density of 0.3 W cm-3 . As a demonstration of practical application, a red light emitting diode can be lighted up by three hybrid devices connected in series.

Double and Triple Si-H-M Bridge Bonds: Matrix Infrared Spectra and Theoretical Calculations for Reaction Products of Silane with Ti, Zr, and Hf Atoms.

Infrared spectra of matrix isolated dibridged Si(µ-H)2MH2 and tribridged Si(µ-H)3MH molecules (M = Zr and Hf) were observed following the laser-ablated metal atom reactions with SiH4 during condensation in excess argon and neon, but only the latter species was observed with titanium. Assignments of the major vibrational modes, which included terminal MH, MH2 and hydrogen bridge Si-H-M stretching modes, were confirmed by the appropriate SiD4 isotopic shifts and density functional vibrational frequency calculations (B3LYP and BPW91). The Si-H-M hydrogen bridge bond is calculated as weak covalent interaction and compared with the C-H···M agostic interaction in terms of electron localization function (ELF) analysis and noncovalent interaction index (NCI) calculations. Furthermore, the different products of Ti, Zr, and Hf reactions with SiH4 are discussed in detail.

Randomized, Double-Blind, Phase III Trial of Enzastaurin Versus Placebo in Patients Achieving Remission After First-Line Therapy for High-Risk Diffuse Large B-Cell Lymphoma.

PURPOSE: To compare disease-free survival (DFS) after maintenance therapy with the selective protein kinase C ß (PKCß) inhibitor, enzastaurin, versus placebo in patients with diffuse large B-cell lymphoma (DLBCL) in complete remission and with a high risk of relapse after first-line therapy. PATIENTS AND METHODS: This multicenter, phase III, randomized, double-blind, placebo-controlled trial enrolled patients who were at high risk of recurrence after rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Patients (N = 758) with stage II bulky or stage III to IV DLBCL, three or more International Prognostic Index risk factors at diagnosis, and a complete response or unconfirmed complete response after 6 to 8 cycles of R-CHOP were assigned 2:1 to receive oral enzastaurin 500 mg daily or placebo for 3 years or until disease progression or unacceptable toxicity. Primary end point was DFS 3 years after the last patient entered treatment. Correlative analyses of biomarkers, including cell of origin by immunohistochemistry and PKCß expression, with efficacy outcomes were exploratory objectives. RESULTS: After a median follow-up of 48 months, DFS hazard ratio for enzastaurin versus placebo was 0.92 (95% CI, 0.689 to 1.216; two-sided log-rank P = .541; 4-year DFS, 70% v 71%, respectively). Independent of treatment, no significant associations were observed between PKCß protein expression or cell of origin and DFS or overall survival. CONCLUSION: Enzastaurin did not significantly improve DFS in patients with high-risk DLBCL after achieving complete response to R-CHOP. Achievement of a complete response may have abrogated the prognostic significance of cell of origin by immunohistochemistry.

A First-in-Human Phase I Study of the Oral p38 MAPK Inhibitor, Ralimetinib (LY2228820 Dimesylate), in Patients with Advanced Cancer.

PURPOSE: p38 MAPK regulates the production of cytokines in the tumor microenvironment and enables cancer cells to survive despite oncogenic stress, radiotherapy, chemotherapy, and targeted therapies. Ralimetinib (LY2228820 dimesylate) is a selective small-molecule inhibitor of p38 MAPK. This phase I study aimed to evaluate the safety and tolerability of ralimetinib, as a single agent and in combination with tamoxifen, when administered orally to patients with advanced cancer. EXPERIMENTAL DESIGN: The study design consisted of a dose-escalation phase performed in a 3+3 design (Part A; n = 54), two dose-confirmation phases [Part B at 420 mg (n = 18) and Part C at 300 mg (n = 8)], and a tumor-specific expansion phase in combination with tamoxifen for women with hormone receptor-positive metastatic breast cancer refractory to aromatase inhibitors (Part D; n = 9). Ralimetinib was administered orally every 12 hours on days 1 to 14 of a 28-day cycle. RESULTS: Eighty-nine patients received ralimetinib at 11 dose levels (10, 20, 40, 65, 90, 120, 160, 200, 300, 420, and 560 mg). Plasma exposure of ralimetinib (Cmax and AUC) increased in a dose-dependent manner. After a single dose, ralimetinib inhibited p38 MAPK-induced phosphorylation of MAPKAP-K2 in peripheral blood mononuclear cells. The most common adverse events, possibly drug-related, included rash, fatigue, nausea, constipation, pruritus, and vomiting. The recommended phase II dose was 300 mg every 12 hours as monotherapy or in combination with tamoxifen. Although no patients achieved a complete response or partial response,19 patients (21.3%) achieved stable disease with a median duration of 3.7 months, with 9 of these patients on study for ≥ 6 cycles. CONCLUSIONS: Ralimetinib demonstrated acceptable safety, tolerability, and pharmacokinetics for patients with advanced cancer.