Mutational signature and prognosis in adenocarcinoma of the bladder.

Adenocarcinoma of the bladder is a rare urinary bladder carcinoma with limited therapy options due to lack of molecular characterization. Here, we aimed to reveal the mutational and transcriptomic landscapes of adenocarcinoma of the bladder and assess any relationship with prognosis. Between February 2015 and June 2021, a total of 23 patients with adenocarcinoma of the bladder were enrolled. These included 16 patients with primary bladder adenocarcinomas and seven patients with urachal adenocarcinoma. Whole exome sequencing (16 patients), whole genome sequencing (16 patients), bulk RNA sequencing (RNA-seq) (19 patients), and single-cell RNA-seq (5 patients) were conducted for the specimens. Correlation analysis, survival analysis, and t-tests were also performed. Prevalent T>A substitutions were observed among somatic mutations, and major trinucleotide contexts included 5'-CTC-3' and 5'-CTG-3'. This pattern was mainly contributed by COSMIC signature 22 related to chemical carcinogen exposure (probably aristolochic acid), which has not been reported in bladder adenocarcinoma. Moreover, genes with copy number changes were also enriched in the KEGG term 'chemical carcinogenesis'. Transcriptomic analysis suggested high immune cell infiltration and luminal-like features in the majority of samples. Interestingly, a small fraction of samples with an APOBEC-derived mutational signature exhibited a higher risk of disease progression compared with samples with only a chemical carcinogen-related signature, confirming the molecular and prognostic heterogeneity of bladder adenocarcinoma. This study presents mutational and transcriptomic landscapes of bladder adenocarcinoma, and indicates that a chemical carcinogen-related mutational signature may be related to a better prognosis compared with an APOBEC signature in adenocarcinoma of the bladder. © 2024 The Pathological Society of Great Britain and Ireland.

Boosting Polysulfide Redox Kinetics by Temperature-Induced Metal-Insulator Transition Effect of Tungsten-Doped Vanadium Dioxide for High-Temperature Lithium-Sulfur Batteries.

The practical application of Li-S batteries is still severely restricted by poor cyclic performance caused by the intrinsic polysulfides shuttle effect, which is even more severe under the high-temperature condition owing to the inevitable increase of polysulfides' solubility and diffusion rate. Herein, tungsten-doped vanadium dioxide (W-VO2) micro-flowers are employed with first-order metal-insulator phase transition (MIT) property as a robust and multifunctional modification layer to hamper the shuttle effect and simultaneously improve the thermotolerance of the common separator. Tungsten doping significantly reduces the transition temperature from 68 to 35 °C of vanadium dioxide, which renders the W-VO2 easier to turn from the insulating monoclinic phase into the metallic rutile phase. The systematic experiments and theoretical analysis demonstrate that the temperature-induced in-suit MIT property endows the W-VO2 catalyst with strong chemisorption against polysulfides, low energy barrier for liquid-to-solid conversion, and outstanding diffusion kinetics of Li-ion under high temperatures. Benefiting from these advantages, the Li-S batteries with W-VO2 modified separator exhibit significantly improved rate and long-term cyclic performance under 50 °C. Remarkably, even at an elevated temperature (80 °C), they still exhibit superior electrochemical performance. This work opens a rewarding avenue to use phase-changing materials for high-temperature Li-S batteries.

Optimizing Surface State Electrons of Topological Semi-Metal by Atomic Doping for Enhanced Hydrogen Evolution Reaction.

Topological materials carrying topological surface states (TSSs) have extraordinary carrier mobility and robustness, which provide a new platform for searching for efficient hydrogen evolution reaction (HER) electrocatalysts. However, the majority of these TSSs originate from the sp band of topological quantum catalysts rather than the d band. Here, based on the density functional theory calculation, it is reported a topological semimetal Pd3Sn carrying TSSs mainly derived from d orbital and proposed that optimizing surface state electrons of Pd3Sn by introduction heteroatoms (Ni) can promote hybridization between hydrogen atoms and electrons, thereby reducing the Gibbs free energy (ΔGH) of adsorbed hydrogen and improving its HER performance. Moreover, this is well verified by electrocatalytic experiment results, the Ni-doped Pd3Sn (Ni0.1Pd2.9Sn) show much lower overpotential (-29 mV vs RHE) and Tafel slope (17 mV dec-1) than Pd3Sn (-39 mV vs RHE, 25 mV dec-1) at a current density of 10 mA cm-2. Significantly, the Ni0.1Pd2.9Sn nanoparticles exhibit excellent stability for HER. The electrocatalytic activity of Ni0.1Pd2.9Sn nanoparticles is superior to that of commercial Pt. This work provides an accurate guide for manipulating surface state electrons to improve the HER performance of catalysts.

Modulating d-Band Electronic Structures of Molybdenum Disulfide via p/n Doping to Boost Polysulfide Conversion in Lithium-Sulfur Batteries.

Polysulfide shuttle effect and sluggish sulfur reaction kinetics severely impede the cycling stability and sulfur utilization of lithium-sulfur (Li-S) batteries. Modulating d-band electronic structures of molybdenum disulfide electrocatalysts via p/n doping is promising to boost polysulfide conversion and suppress polysulfide migration in lithium-sulfur batteries. Herein, p-type V-doped MoS2 (V-MoS2 ) and n-type Mn-doped MoS2 (Mn-MoS2 ) catalysts are well-designed. Experimental results and theoretical analyses reveal that both of them significantly increase the binding energy of polysulfides on the catalysts' surface and accelerate the sluggish conversion kinetics of sulfur species. Particularly, the p-type V-MoS2 catalyst exhibits a more obvious bidirectional catalytic effect. Electronic structure analysis further demonstrates that the superior anchoring and electrocatalytic activities are originated from the upward shift of the d-band center and the optimized electronic structure induced by duplex metal coupling. As a result, the Li-S batteries with V-MoS2 modified separator exhibit a high initial capacity of 1607.2 mAh g-1 at 0.2 C and excellent rate and cycling performance. Moreover, even at a high sulfur loading of 6.84 mg cm-2 , a favorable initial areal capacity of 8.98 mAh cm-2 is achieved at 0.1 C. This work may bring widespread attention to atomic engineering in catalyst design for high-performance Li-S batteries.

Self-Supporting Multicomponent Hierarchical Network Aerogel as Sulfur Anchoring-Catalytic Medium for Highly Stable Lithium-Sulfur Battery.

The low utilization rate of active materials, shuttle effect of lithium polysulfides (LiPSs), and slow reaction kinetics lead to the extremely low efficiency and poor high current cycle stability of lithium sulfur batteries (Li-S batteries). In this paper, a self-supporting multicomponent hierarchical network aerogel is proposed as the modified cathode (S/GO@MX@VS4 ). It consists of graphene (GO) and MXene nanosheets (MX) loaded with VS4 nanoparticles. The experimental results and first-principles calculations show that the GO@MX@VS4 aerogel has strong adsorption and reversible conversion effects on LiPSs. It can not only inhibit the shuttle effect and improve the utilization rate of active substances by keeping the chain crystal structure of VS4 , but also promote the reversibility and kinetics of the reaction by accelerating the liquid-solid transformation in the reduction process and the decomposition of insoluble Li2 S in the oxidation process. The GO@MX@VS4 aerogel modified cathode with a multicomponent synergy exhibits the capacity ratios (Q1 /Q2 ) at different discharge stages is close to the theoretical value (1:2.8), and the capacity decay per cycle is 0.019% in 1200 cycles at 5C. Also, a high areal capacity of 6.90 mAh cm-2 is provided even at high sulfur loading (7.39 mg cm-2 ) and low electrolyte/sulfur ratio (E/S, 8.0 µL mg-1 ).

Quenching and Electrical Current Poling Effect on Improved Ferroelectric and Piezoelectric Properties in BiFeO3-Based High-Temperature Piezoceramics.

The effects of quenching on the structural, electrical, dielectric, ferroelectric (FE), and piezoelectric properties are investigated systematically in the 0.85BiFe1-xCrxO3-0.15BaTi1-xMnxO3 (0 ≤ x ≤ 0.03) ceramics. Optimal piezoelectricity and FE Curie temperature are obtained through optimized quenching rate and temperature. Quenching effect on piezoelectricity is especially significant for the samples near morphotropic phase boundaries (MPB), which can be ascribed to quenching-induced changes in phase ratio (rhombohedral and tetragonal phase) and domain structure/defect dipole orientation. Moreover, a new poling method, that is, cooling the sample at a constant dc current across FE TC, is established to improve the piezoelectricity. This work not only reveals the possible mechanism of quenching effect on the improved piezoelectricity in the BFO-based piezoceramics (especially near the MPB) but also suggests an electric current poling strategy for improving piezoelectricity by suppressing the defect dipole effects in BFO-based and even other piezoelectrics.

Prevalence and correlative factors of hyperhomocysteinemia in elderly patients with femoral neck fracture: A cross-sectional study.

AIMS: The occurrence of hyperhomocysteinemia (HHcy) in elderly patients with femoral neck fracture (FNF) draws little attention from surgeons preoperatively. The aim of our study was to determine the prevalence and correlative factors of HHcy in elderly patients (≥65 years) with FNF prior to surgery. METHODS: We retrospectively investigated 286 elderly FNF patients aged 65-98 years admitted to our institution from September 2020 to September 2021. Categorical variables were compared using the Chi-squared test, and continuous variables were compared using the Mann-Whitney U test. Univariable and multivariable logistic regression were used to determine the associations of variables with the odds of HHcy. RESULTS: Among the 286 elderly FNF patients, the prevalence of HHcy was 30.77% and the mean Hcy level was 14.52 ± 10.49 µmol/L. The mean Hcy level and the prevalence of HHcy in male patients were significantly higher than that in female patients (16.41 ± 9.58 µmol/L vs. 14.00 ± 10.69 µmol/L, p = 0.002; 43.55% vs. 27.23%, p = 0.014). Multivariate analysis indicated that being male patient (OR 2.187, 95% CI 1.187-4.028, p = 0.012), hypertension (OR 1.993, 95% CI 1.141-3.479, p = 0.015), and low HDL-C (OR 2.979, 95% CI 1.353-6.558, p = 0.007) were significant correlative factors of HHcy among elderly FNF patients. CONCLUSIONS: This study found a high prevalence of HHcy in elderly FNF patients, with being male patient, hypertension, and low levels of HDL-C as the significant correlative factors after adjusting for age and other covariables. However, further large-scale studies in wider regions are warranted to confirm these findings.

The impact of novel anchored barbed suture for capsular closure on hospital length of stay after total knee arthroplasty: a retrospective cohort study.

OBJECTIVE: The aim was to evaluate whether using novel anchored barded suture for capsular closure can further shorten the length of stay following primary total knee arthroplasty (TKA) within existed enhanced recovery after surgery (ERAS) protocol in osteoarthritis patients. METHODS: A retrospective cohort study was conducted among osteoarthritis patients aged 18 to 80 years without major comorbidities who underwent primary unilateral TKA between January 2018 and December 2019 was conducted. The capsular closure techniques, interventions for ERAS, operation time and length of stay were collected via hospital electronic information system. Propensity-score matching was used to compensate for the difference in interventions for ERAS and patient characteristics. Subgroup comparison of patients treated under normal ERAS protocol was performed. RESULTS: Included were 315 patients with capsular closure by barded suture and 397 patients with interrupted capsular closure by traditional suture. Patients' characteristics and interventions for ERAS were balanced after propensity-score matching. The average postoperative length of stay in barded suture group was shorter than the compared group (2.10 ± 0.57 vs. 2.33 ± 0.80 days, p = 0.004), and with a significantly higher proportion of patients discharging within 2 days post procedure (88.0% vs. 70.7%, p < 0.001). The operation time for patients with barded suture closure was shorter compared to interrupted closure technique (100.90 ± 16.59 vs. 105.52 ± 18.47 min, p = 0.004). Subgroup analysis of patients treated under different levels ERAS protocol showed comparable results. CONCLUSION: The use of barded suture for capsular closure was associated with shorter length of stay after TKA compared to traditional suture, suggesting that barded suturing technique could be one effective intervention for ERAS.

Mid-term results of giant cell tumours with pathologic fractures around the knee: a multicentre retrospective study.

OBJECTIVE: The aims of this work are to present a classification of "complex fracture" and "simple fracture", to compare their features, treatments and prognosis in patients with giant cell tumour with pathologic fractures around the knee, and to determine the best surgical method for patients who have giant cell tumour around the knee with different degrees of fracture. METHODS: Data from 130 patients with pathologic fractures from giant cell tumour around the knee who underwent surgical treatment from March 2000 to November 2015 at 6 institutes around China were collected and analysed. A multicentric study design was used to explore the epidemiological features and to compare differences in the surgical procedures and prognosis of the two fracture groups. The mean age at diagnosis was 37.1 years old (range, 13-77 years). The median follow-up was 126.5 months, ranging from 68 to 370 months. RESULTS: The general clinical and imaging features of the groups of patients with simple and complex fractures, namely, sex, age, the lesion site, living or working environment, eccentric growth patterns, Campanacci grading system, and duration of symptoms before treatment, showed varying degrees of differences, but with no statistical significance (p > 0.05). The incidence rate of surrounding soft tissue mass was 35.2% (32/91) in the group with simple fractures, whereas it was 87.2% (34/39) in the group with complex fractures, which showed a significant difference (p < 0.05). Wide resection and reconstruction with joint replacement were performed more often in patients with complex fractures (61.5%, 24/39). Intralesional procedures were performed more often in patients with simple fractures (56.0%, 51/91). The difference showed significant differences (p < 0.05). The local recurrence rate was 17.6% (16/91) in the group with simple fractures, whereas it was 10.3% (4/39) in the complex fracture group, showing a significant difference (p < 0.05). A total of 2.3% of patients (n = 3,3/130) developed a skip lesion. The complication rates were 4.6% (4/87) and 14.7% (5/34), respectively, in the two groups with simple or complex fractures, showing a significant difference (p < 0.05). The mean MSTS and TESS scores with simple fractures were 26.6 (range, 13-30) and 84.1 (range, 29-100), respectively, whereas the mean scores in the group with complex fractures were 25.5 (range, 18-30) and 78.3 (range, 30-100), respectively, also showing a significant difference (p < 0.05). CONCLUSION: Our classification of "simple fracture" and "complex fracture" could guide decisions regarding the best surgical method for lesions in patients who have giant cell tumour around the knee with different degrees of fracture.

Atomically Precise Synthesis and Characterization of Heptauthrene with Triplet Ground State.

By virtue of multitunable spin structures upon designing the π-electron topologies, phenalenyl-based nanographenes are of substantial interest in fundamental science and for potential applications in spintronics. Heptauthrene, as one of the well-known phenalenyl diradicals, is composed of one benzene-fused bisphenalenyls in mirror symmetry and expected to have a triplet ground state. However, the synthesis of unsubstituted heptauthrene remains very challenging due to the high reactivity of triplet diradicals. Here, we report a combined in-solution and on-surface synthesis of unsubstituted heptauthrene, whose chemical structure is characterized through bond-resolved atomic force microscopy. Combined with mean-field Hubbard model calculations, its triplet ground state is unambiguously confirmed by the underscreened Kondo resonance in response to the magnetic field, as well as the engineered spin-state switching upon extra hydrogen atom addition and dissociation on the radical site. Our results provide access to phenalenyl-based nanographenes with high-spin ground state, potentially useful in constructing high-spin networks.

miR-146a interacting with lncRNA EPB41L4A-AS1 and lncRNA SNHG7 inhibits proliferation of bone marrow-derived mesenchymal stem cells.

Emerging evidence suggests that microRNA plays a pivotal role in cell proliferation. Our previous research has certified that miR-146a attenuates osteoarthritis through the regulation of cartilage homeostasis. However, little information about the function of miR-146a in bone marrow-derived mesenchymal stem cells (BMSCs) proliferation and the underlying mechanism was available. Therefore, this study aims at investigating the role of miR-146a on the proliferation of BMSCs and the possible mechanisms involved. The function of miR-146a on BMSCs proliferation was studied through overexpression and knockdown of miR-146a or the indicated long noncoding RNAs (lncRNAs) in BMSCs and then the proliferation rate of the BMSCs were detected by Cell Counting Kit-8 assay, colony formation assay. Besides, flow cytometry was used to test the cell cycle state of BMSCs modified by overexpression or knockdown of miR-146a or lncRNA EPB41L4A-AS1 (EPB41L4A Antisense RNA 1) and small nucleolar RNA host gene 7 (SNHG7). The expression level of marker genes involved in modulating cell proliferation was evaluated by quantitative polymerase chain reaction and western blot analysis. We discovered that the knockdown of miR-146a significantly promoted BMSCs proliferation. Moreover, miR-146a could bind to and inhibit endogenous expression of EPB41L4A-AS1 and SNHG7. Further study demonstrated that overexpression of EPB41L4A-AS1 and SNHG7 significantly enhanced proliferation of BMSCs. For the first time, we certified that miR-146a suppressed BMSCs proliferation, but EPB41L4A-AS1 and SNHG7 promoted BMSCs proliferation in the present study. Mechanistically, miR-146a significantly inhibited BMSCs proliferation partly through miR-146a/EPB41L4A-AS1 SNHG7/cell proliferation signaling pathway axis.

Interleukin-38 in colorectal cancer: a potential role in precision medicine.

Colorectal cancer (CRC) is a leading cause of cancer-related death, partly due to a lack of reliable biomarkers for early diagnosis. To improve the outcome of CRC, it is critical to provide diagnosis at an early stage using promising sensitive/specific marker(s). Using immunohistochemistry and histopathology, IL-38 expression was determined in tissue arrays of CRC with different TNM status and depth of tumour invasion. Data were compared to IL-38 in adjacent non-cancer tissue and correlated with demographic information, including survival. A substantial reduction of IL-38 was detected in the CRC tissue compared to adjacent non-cancer colonic tissue. IL-38 correlated with the extent of tumour differentiation (P < 0.0001); CRC location in the left side of the colon (P < 0.05), and smaller tumour size (≤ 5 cm; P < 0.05). Receiver operating characteristic (ROC) curve analysis demonstrated both high specificity and high sensitivity of IL-38 for the diagnosis of CRC [area under the curve (AUC) = 0.89)]. By sub-group analysis, AUC of IL-38 for the diagnosis of CRC was higher in poorly differentiated, right-sided CRC or tumour size > 5 cm (all AUC > 0.9). Significantly, longer survival was observed for the IL-38high versus the IL-38low groups in CRC patients (P = 0.04). Survival was also longer for IL-38high patients with lymph node metastasis (P = 0.01) and TNM stage III-IV (P = 0.02). Multivariate analysis demonstrated that IL-38 (P = 0.05) and tumour invasion depth (P = 0.04) were independent factors for survival. High IL38 in CRC is an independent prognostic factor for the longer survival of CRC patients. IL-38 signalling may constitute a therapeutic target in CRC.

IL-36 s in the colorectal cancer: is interleukin 36 good or bad for the development of colorectal cancer?

BACKGROUND AND AIMS: Colorectal cancer (CRC) is a major killer. Host immunity is important in tumorigenesis. Direct comparison among IL-36α, IL-36ß and IL-36γ in the prognosis of CRC is unclear. METHODS: CRC tissue arrays were generated from colorectostomy samples with TNM stage, invasion depth and the demography of these patients (n = 185). Using immunohistochemistry/histopathology, IL-36α, IL-36ß and IL-36γ were determined, in comparison to non-cancer tissues. RESULTS: A significant association was observed between colonic IL-36α, IL-36ß or IL-36γ and the presence of cancer (with all P < 0.0001). Using ROC curve analysis, specificity and sensitivity of IL-36α, IL-36ß or IL-36γ were confirmed, with area under the curve (AUC) values of 0.68, 0.73 and 0.65, respectively. Significant differences in survival were observed between IL-36αhigh and IL-36αlow (P = 0.003) or IL-36γhigh and IL-36γlow (P = 0.03). Survival curves varied significantly when further stratification into sub-groups, on the basis of combined levels of expression of two isotypes of IL-36 was undertaken. A significant difference was observed when levels of IL-36α and IL-36ß were combined (P = 0.01), or a combination of IL-36α plus IL-36γ (P = 0.002). The sub-groups with a combination of IL-36αhigh plus IL-36ßhigh, or IL-36αhigh plus IL-36γlow exhibited the longest survival time among CRC patients. In contrast, the sub-groups of IL-36αlow plus IL-36ßhigh or IL-36αlow plus IL-36γhigh had the shortest overall survival. Using the log-rank test, IL-36αhigh expression significantly improved survival in patients with an invasion depth of T4 (P < 0.0001), lymph node metastasis (P = 0.04), TNM III-IV (P = 0.03) or with a right-sided colon tumour (P = 0.02). Similarly, IL-36γlow expression was significantly associated with improved survival in patients with no lymph node metastasis (P = 0.008), TNM I-II (P = 0.03) or with a left-sided colon tumour (P = 0.05). Multivariate analysis demonstrated that among IL-36α, IL-36ß and IL-36γ, only IL-36α (HR, 0.37; 95% CI, 0.16-0.87; P = 0.02) was an independent factor in survival, using Cox proportional hazards regression analysis. CONCLUSION: IL-36α or IL-36γ are reliable biomarkers in predicting the prognosis of CRC during the later or early stages of the disease, respectively. Combining IL-36α plus IL-36γ appears to more accurately predict the postoperative prognosis of CRC patients. Our data may be useful in the management of CRC.

The challenge of safe anesthesia in developing countries: defining the problems in a medical center in Cambodia.

BACKGROUND: The International Standards for a Safe Practice of Anesthesia (ISSPA) were developed on behalf of the World Federation of Societies of Anaesthesiologists and the World Health Organization. It has been recommend as an assessment tool that allows anesthetic providers in developing countries to assess their compliance and needs. This study was performed to describe the anesthesia service in one main public hospital during an 8-month medical mission in Cambodia and evaluate its anesthetic safety issues according to the ISSPA. METHODS: We conduct a retrospective study involving 1953 patients at the Preah Ket Mealea hospital. Patient demographics, anesthetic techniques, and complications were reviewed according to the registers of the anesthetic services and questionnaires. The inadequacies in personnel, facilities, equipment, medications, and conduct of anesthesia drugs were recorded using a checklist based on the ISSPA. RESULTS: A total of 1792 patients received general and regional anesthesia in the operating room, while 161 patients receiving sedation for gastroscopy. The patients' mean age was 45.0 ± 16.6 years (range, 17-87 years). The three most common surgical procedures were abdominal (52.0%; confidence interval [CI], 49.3-54.7), orthopedic (27.6%; CI, 25.2-29.9), and urological surgery (14.7%; CI, 12.8-16.6). General anesthesia, spinal anesthesia, and brachial plexus block were performed in 54.3% (CI, 51.7-56.8), 28.2% (CI, 25.9-30.5), and 9.4% (CI, 7.9-10.9) of patients, respectively. One death occurred. Twenty-six items related to professional aspects, monitoring, and conduct of anesthesia did not meet the ISSPA-recommended standards. A lack of commonly used drugs and monitoring equipment was noted, posing major threats to the safety of anesthesia practice, especially in emergency situations. CONCLUSIONS: This study adds to the scarce literature on anesthesia practice in low- and middle-income countries such as Cambodia. Future medical assistance should help to strengthen these countries' inadequacies, allowing for the adoption of international standards for the safe practice of anesthesia.

[Rotective Effects of Quercetin Against the Triptolide Induced Liver Injury and Relevant Mechanism Study].

OBJECTIVE: To explore the protective effects of quercetin (QE) on triptolide (TP) induced liver injury and the relevant mechanism. METHODS: Forty C57BL/6 mice were equally divided into 4 groups, control group, TP model group, 20 mg/kg QE treatment group and 80 mg/kg QE treatment group randomly. The 20 mg/kg and 80 mg/kg QE groups were gastrointestinal administration with QE at the dose of 0.2 mL/10 g for 10 d, twice daily, while other groups were administrated with equivalent normal saline. Four hours post the last dose, animals were gastrointestinal administered with TP at a dose of 500 µg/kg per mouse, except for NS control. All the mice were sacrificed 22 h later, blood and liver tissue samples were collected. The pathologic change of liver tissue was detected by HE staining. The level of aminotransferase (AST) and aspartate alanine aminotransferase (ALT) in serum, and the level of glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD) in liver tissue homogenates were detected using the commercial kits. The level of interleukin (IL)-17, IL-10 and IL-6 in liver tissue homogenates was measured by ELISA. Hepatic expression of Toll-like receptor 4 (TLR4) was detected by Western blot. RESULTS: Compared with the control group, in the TP model group, hepatic lobule structure atrophied and even disappeared, hepatic cell necrosis and inflammatory cell infiltration are obvious. Additionally, in TP model group, serum ALT, AST and MDA levels were significantly increased, SOD and GSH levels were decreased, IL-6 and IL-17 levels were increased, IL-10 levels were decreased, and TLR4 protein levels were increased (P < 0.05). Compared with the TP model group, liver tissue injury and inflammatory cell infiltration were reduced in the QE group, and serum levels of ALT, AST, MDA, IL-6 and IL-17 were all decreased. TLR4 expression was down-regulated (P < 0.05) in both QE groups, and the decease levle was more significant in the high-dose QE group (P < 0.05, compared with the low-dose QE group). CONCLUSION: Quercetin can reduce TP-induced liver injury by reducing oxidative damage, promoting antioxidant and regulating cytokine secretion.

Hypoxia/reoxygenation-induced HMGB1 translocation and release promotes islet proinflammatory cytokine production and early islet graft failure through TLRs signaling.

High-mobility group box 1 (HMGB1) translocation and release, which is involved in several tissue types of ischemia-reperfusion injuries, activate innate immunity by inducing proinflammatory cytokine production through its interaction with toll-like receptors (TLRs). Our objective was to determine the role of HMGB1 and the degree of activation of TLR-related signal transduction pathways in hypoxia/reoxygenation (H/R)-induced proinflammatory cytokine production and intra-islet graft inflammation. After islets are exposed to hypoxia-reoxygenation for 24h, TLR2/4 expression and TLR-mediated signaling was up-regulated in islets, and HMGB1 was translocated from the nucleus to the cytoplasm and released to the extracellular space. With H/R exposure, proinflammatory cytokine production (IL-1ß and TNF-α) and islet injury were significantly increased, and these effects depend on TLR2/4 signaling pathways. Exogenous HMGB1 also induces islet inflammation and increases the phosphorylation of STAT3, p38 and IκBα in wild-type islets. TLR2 deficiency in TLR2-KO islets resulted in the inhibition of IL-1ß production and STAT3/p38 phosphorylation after HMGB1 exposure. TLR4 deficiency in TLR4-KO islets resulted in the inhibition of TNF-α production and IκBα phosphorylation after HMGB1 exposure. Pre-incubation of the STAT3, p38, or NF-κB inhibitors significantly inhibited HMGB1-induced IL-1ß or TNF-α production in islets, but the effect of HMGB1 or H/R-induced islet injury was not counteracted by a separate treatment of the STAT3 inhibitor, p38 inhibitor, or NF-κB inhibitors. HMGB1 inhibition by ethyl pyruvate or blockade by neutralizing antibodies significantly decreased the phosphorylation of STAT3, p38 and IκBα, the production of IL-1ß and TNF-α, and the islet injury in wild-type islets after exposure to H/R and significantly improved early islet graft failure. Thus, our results suggest that HMGB1 released from H/R induced islets works in an autocrine manner to up-regulate STAT or p38 and augment IL-1ß production via TLR2, and up-regulate NF-κB and augment TNF-α production via TLR4 in intra-islet, which are associated with H/R-induced islet injury and early graft failure.

Engineering magnetic anisotropy and magnetization switching in multilayers by strain.

The effect of the strain on the magnetic properties of metallic multilayers has been investigated by ab initio studies. Our results indicate that the magnetic anisotropy energy (MAE) of an Fe(001) surface can be drastically enhanced by capping with 5d elements. By choosing Ir-Fe multilayers as a model system, we demonstrate that the MAE which depends on the composition and the structure of the multilayers can be tuned in a large range by strain. Furthermore, our results show that not only the amplitude of the MAE but also the easy axis of Pt-Fe multilayers can be engineered by strain. Magnetization switching by strain is also investigated.

Arthroscopic reduction and fixation for displaced greater tuberosity fractures using the modified suture-bridge technique.

PURPOSE: The aim of this study was to evaluate the early clinical outcomes of arthroscopic treatment of avulsion or comminuted fractures of the greater tuberosity (GT) using a modified suture-bridge technique. METHODS: Between February 2013 and November 2015, 14 patients with displaced or comminuted fractures of GT were arthroscopically treated using a modified suturebridge technique. Displacement of the GT fragments was > 3 mm in any plane. An analysis of follow-up results including the University of California, Los Angeles (UCLA) shoulder scale; the shoulder index of the American Shoulder and Elbow Surgeons (ASES); the simple shoulder test (SST); and shoulder range of motion (ROM), is presented. RESULTS: Mean duration of follow up is 18.9 months (range, 6-30). Mean age of patients was 62.9 years (range, 49-74). Postoperatively, the outcomes were rated as excellent, good and fair in two, 11 and one patient, respectively based on the UCLA score. At the most recent follow-up, the average UCLA score increased to 32 points, the ASES score increased to 97.5 points, and the SST score increased to 11 points. Average forward flexion was 153.6°, average abduction was 158.6°, average external rotation in the neutral position was 38.6°, and internal rotation increased to the 12th thoracic vertebral level. CONCLUSION: Early follow-up outcomes of the arthroscopic modified suture-bridge technique used for avulsion or comminuted GT fractures are promising. The technique can be used as one of the therapeutic modalities for GT fractures.

TAK-242 attenuates acute cigarette smoke-induced pulmonary inflammation in mouse via the TLR4/NF-κB signaling pathway.

The present study determined the effect of TAK-242 on attenuating acute cigarette smoke induced pulmonary inflammation and attempted to dissect its underlying mechanisms of action. When administered to the C57BL/6J mice after a 3 days period of cigarettes exposure,TAK-242 significantly decreased the accumulation of macrophages, neutrophils, lymphocytes and DCs, and upregulation of IL-6, IL-8 and TNF-α in BAL fluid and lungs in a dose-dependent manner, except MCP-1, IL-1ß and IFN-γ, which demonstrated that TAK-242 inhibits release of various inflammatory mediators induced by cigarette smoke. TAK-242 also significantly suppressed the expression of TLR4, MyD88 and the activation of NF-κB in lungs, suggesting that TAK-242-mediated inhibition occurred largely through the TLR4/NF-κB signal pathway. Our results support TAK-242 as a potent therapeutic agent in the treatment of cigarette smoke induced-pulmonary inflammation, and warrants further pharmaceutical investigation.