A self-powered implantable and bioresorbable electrostimulation device for biofeedback bone fracture healing.

Electrostimulation has been recognized as a promising nonpharmacological treatment in orthopedics to promote bone fracture healing. However, clinical applications have been largely limited by the complexity of equipment operation and stimulation implementation. Here, we present a self-powered implantable and bioresorbable bone fracture electrostimulation device, which consists of a triboelectric nanogenerator for electricity generation and a pair of dressing electrodes for applying electrostimulations directly toward the fracture. The device can be attached to irregular tissue surfaces and provide biphasic electric pulses in response to nearby body movements. We demonstrated the operation of this device on rats and achieved effective bone fracture healing in as short as 6 wk versus the controls for more than 10 wk to reach the same healing result. The optimized electrical field could activate relevant growth factors to regulate bone microenvironment for promoting bone formation and bone remodeling to accelerate bone regeneration and maturation, with statistically significant 27% and 83% improvement over the control groups in mineral density and flexural strength, respectively. This work provided an effective implantable fracture therapy device that is self-responsive, battery free, and requires no surgical removal after fulfilling the biomedical intervention.

SERPINA1 and plasminogen as novel biomarkers in obstetric antiphospholipid syndrome patients.

OBJECTIVES: To explore the potential biomarkers and mechanisms in obstetric antiphospholipid syndrome (OAPS) patients by placental proteomics. METHODS: Among 212 follow-up pregnancy patients based on the Chinese Rheumatism Data Center database (CRDC), we continuously recruited 30 pregnancy patients at the late stage of pregnancy for proteomics study. Fresh placental tissues were collected and 4D label-free technologies were used to analyse the placental proteome in patients. Bioinformatic analysis was applied to identify differentially expressed proteins (DEPs) and crucial pathways. Placental tissues were also stained with haematoxylin and eosin (H & E) for histological analysis. RESULTS: We collected 7 OAPS patients (33.85±1.57 years), 4 SAPS patients (34.25 ± 3.86 years), 8 SLE patients (30.38±2.56 years), and 11 healthy controls (31.45±3.01 years). All patients in the SAPS and OAPS group had adverse pregnancy history. A total of 7040 proteins containing at least one unique peptide were identified. There were 214 DEPs between the healthy group and the OAPS group, of which 82 proteins were upregulated and 132 proteins were downregulated in the OAPS group based on fold change ≥1.5 and p-values ≤0.05. We found that the complement and coagulation pathway played a significant role in OAPS patients. Several key proteins (C1Q, C4b, SERPINA1, plasminogen) highly expressed in placental tissues, that may serve as biomarkers for OAPS patients. CONCLUSIONS: The complement and coagulation pathway and related DEPs (SERPINA1 and plasminogen) were of crucial importance in OAPS patients.

Sorafenib plus hepatic arterial infusion chemotherapy versus sorafenib alone for advanced hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND: The combination of sorafenib and hepatic arterial infusion chemotherapy (HAIC) is expected to exert a synergistic anticancer effect. We conducted this systematic review to examine the efficacy and safety of sorafenib plus HAIC vs sorafenib alone for advanced hepatocellular carcinoma (HCC). METHODS: We systematically searched the PubMed, Embase, and Cochrane Library with the following search terms: "sorafenib," "hepatic arterial infusion chemotherapy," "HAIC," "advanced," "hepatocellular carcinoma," and "HCC." Pooled hazard ratios (HRs) and 95% CIs were calculated for overall survival (OS) and progression-free survival (PFS), and we calculated the pooled risk ratios (RRs) and 95% CIs for objective response rate (ORR) and adverse events (AEs). RESULTS: We found that sorafenib plus HAIC was associated with significantly better OS (HR, 0.56; 95% CI, 0.37-0.83; P < 0.01), PFS (HR, 0.44; 95% CI, 0.27-0.72; P < 0.01), and ORR (RR, 3.77; 95% CI, 1.87-7.58; P < 0.01) than sorafenib alone in advanced HCC. Grade 3/4 AEs were more frequent in the sorafenib plus HAIC group, including leukopenia (RR, 4.54; 95% CI, 1.77-11.64; P < 0.01), neutropenia (RR, 7.81; 95% CI, 3.36-18.16; P < 0.01), thrombocytopenia (RR, 2.97; 95% CI, 1.98-4.46; P < 0.01), anemia (RR, 2.24; 95% CI, 1.22-4.09; P < 0.01), anorexia (RR, 2.37; 95% CI, 1.07-5.27; P = 0.03), nausea (RR, 2.98; 95% CI, 1.19-7.42; P = 0.02), and vomiting (RR, 3.99; 95% CI, 1.14-14.01; P = 0.03). CONCLUSION: Sorafenib plus HAIC improved OS, PFS, and ORR compared with sorafenib alone in advanced HCC, with acceptable safety profile.

Copper-Catalyzed Synthesis of Functionalized Aryl Sulfonamides from Sodium Sulfinates in Green Solvents.

Functionalized aryl sulfonamides are important building blocks in the pharmaceutical industry. A one-step synthesis catalyzed by a copper salt was developed using stable solid commodity chemicals in sulfolane or, alternatively, in green solvents such as γ-valerolactone, iPrOAc, or nBuOAc with acetic acid. The method tolerated diverse functional groups commonly presented in current medicines and drug intermediates. The mechanistic study showed a radical coupling pathway between the sulfonyl and anilinium radicals through the use of K2S2O8 and copper catalyst, respectively.

Risk of osteonecrosis in systemic lupus erythematosus: An 11-year Chinese single-center cohort study.

OBJECTIVE: Osteonecrosis (ON), which can lead to physical disability, is a common complication of systemic lupus erythematosus (SLE). The purpose of this study was to determine the prevalence of ON and identify possible risk factors in Chinese SLE patients. METHODS: SLE patients who fulfilled the 1997 American College of Rheumatology SLE classification criteria were recruited from the Peking Union Medical College Hospital. The chi-square test (χ2 test) and multivariate regression analyses were used to evaluate risk factors. The Cox proportional-hazards model was used to construct the survival curves and estimate the simultaneous effects of prognostic factors on survival. RESULTS: We consecutively enrolled 1,158 patients, of which 88 patients (7.6%) developed ON. Among ON patients, 57.1% of patients had isolated femoral head necrosis and 42.9% had multiple joint involvement. The mean age of ON patients (24.62 ± 8.89 years) was significantly younger than SLE patients without ON (27.23 ± 10.16 years, p = 0.09). The ON group presented with a much longer disease course (10.68 ± 5.97 years, p < 0.001) and increased incidence of arthritis, kidney, and central nervous system (CNS) involvement (65.9% [p < 0.05], 57.6% [p < 0.05], and 16.5% [p < 0.05], respectively, in the ON group). ON patients were more likely to be treated with glucocorticoid (GC) and to receive a high dose of prednisolone at the initial stage of SLE (p < 0.05). The percentage of patients who received hydroxychloroquine was much higher in the control group (p < 0.001). Cox regression analysis suggested that CNS involvement and GC therapy were two independent risk factors for ON in SLE patients. The presence of anti-phospholipid antibodies (aPLs) was a risk factor for multiple joint necrosis (odds ratio: 6.28, p = 0.009). CONCLUSIONS: ON remains a serious and irreversible complication in SLE. In addition to glucocorticoid therapy, we found that CNS system involvement was a risk factor for ON, while the administration of hydroxychloroquine was a protective factor. The clinical characteristics of multiple site ON patients were distinct from isolated femoral head necrosis patients. The presence of aPLs was a risk factor for multiple site osteonecrosis.

Self-powered liquid chemical sensors based on solid-liquid contact electrification.

Triboelectric nanogenerators (TENGs) have attracted many research endeavors as self-powered sensors for force, velocity, and gas detection based on solid-solid or solid-air interactions. Recently, triboelectrification at liquid-solid interfaces also showed intriguing capability in converting physical contacts into electricity. Here, we report a self-powered triboelectric sensor for liquid chemical sensing based on liquid-solid electrification. As a liquid droplet passed across the tribo-negative sensor surface, the induced surface charge balanced with the electrical double layer charge in the liquid droplet. The competition between the double layer charge and surface charge generated characteristic positive and negative voltage spikes, which may serve as a "binary feature" to identify the chemical compound. The sensor showed distinct sensitivity to three amino acids including glycine, lysine and phenylalanine as a function of their concentration. The versatile sensing ability was further demonstrated on several other inorganic and organic chemical compounds dissolved in DI water. This work demonstrated a promising sensing application based on the triboelectrification principle for biofluid sensor development.

The modulatory roles of T cell glycosylation in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a complex and challenging disorder. At present, abnormal T cells are considered to be the key point in the pathogenesis of SLE, including the losing central immune tolerance of self-reactive T cells in the thymus, breaking of regulatory T cell balances, and the overactivation of pro-inflammatory T cells. The alterations of T-cell receptor proteins are closely related to these abnormal changes. Glycosylation is one of the most ubiquitous steps of protein post-translational modification. Especially the modifications of N-glycans and O-glycans on T-cell surfaces have been found to regulate apoptosis and downstream signalling in SLE. Accordingly, this review summarises the aberrant modulate effects of T cell glycosylation in SLE and provides new insights into understanding the pathogenesis and some potential therapeutic targets of this chronic autoimmune disease.

Accelerated complete human skin architecture restoration after wounding by nanogenerator-driven electrostimulation.

BACKGROUND: Electrostimulation (ES) therapy for wound healing is limited in clinical use due to barriers such as cumbersome equipment and intermittent delivery of therapy. METHODS: We adapted a human skin xenograft model that can be used to directly examine the nanogenerator-driven ES (NG-ES) effects on human skin in vivo-an essential translational step toward clinical application of the NG-ES technique for wound healing. RESULTS: We show that NG-ES leads to rapid wound closure with complete restoration of normal skin architecture within 7 days compared to more than 30 days in the literature. NG-ES accelerates the inflammatory phase of wound healing with more rapid resolution of neutrophils and macrophages and enhances wound bed perfusion with more robust neovascularization. CONCLUSION: Our results support the translational evaluation and optimization of the NG-ES technology to deliver convenient, efficient wound healing therapy for use in human wounds.

Prevention of Hepatic Ischemia-Reperfusion Injury by Carbohydrate-Derived Nanoantioxidants.

Hepatic ischemia-reperfusion injury (IRI), which mainly results from excessive reactive oxygen species (ROS) generated by a reperfusion burst of oxygen, has long been a major cause of liver dysfunction and failure after surgical procedures. Here, a monodispersed hydrophilic carbohydrate-derived nanoparticle (C-NP) was synthesized as a nanoantioxidant that could effectively prevent hepatic IRI. The spherical C-NPs had a size of ∼78 ± 11.3 nm covered with polar surface groups. They were well dispersible in water with good colloidal stability, nontoxicity, and good ROS scavenging capability. The C-NPs also exhibited good circulation lifetime, effective delivery to liver, and gradual degradability with an ability to assist the IRI group maintaining a normal and healthy liver status. The pathology mechanism of C-NPs in hepatic IRI was confirmed to be scavenging of excessive ROS by C-NPs. The effective therapeutic treatment of C-NPs in living animals revealed a great potential in clinical prevention for hepatic IRI.

Prediction-based analysis on power consumption gap under long-term emergency: A case in China under COVID-19.

With the coronavirus pandemic wreathing havoc around the world, power industry has been hit hard due to the proposal of lockdown policies. However, the impact of lockdowns and shutdowns on the power system in different regions as well as periods of the pandemic can hardly be reflected on the foundation of current studies. In this paper, a prediction-based analysis method is developed to point out the electricity consumption gap resulted from the pandemic situation. The core of this method is a novel optimized grey prediction model, namely Rolling IMSGM(1,1) (Rolling Mechanism combined with grey model with initial condition as Maclaurin series), which achieves better prediction results in the face of long-term emergencies. A novel initial condition is adopted to track data with various characteristics in the form of higher-order polynomials, which are then determined by intelligent algorithms to realize accurate fitting. Historical power consumption data in China are utilized to carry out the monthly forecasts during COVID-19. Compared with other competitive models' prediction results, the superiority of IMSGM(1,1) are demonstrated. Through analyzing the gap between predicted consumption values and the actual data, it can be found that the impact of the pandemic on electricity varies in different periods, which is related to its severity and the local lockdown policies. This study helps to understand the impact on power industry in the face of such an emergency intuitively so as to respond to possible future events.

Volumetric reduction and dissolution prediction of monosodium urate crystal during urate-lowering therapy - a study using dual-energy computed tomography.

METHODS: Baseline and follow-up DECTs were performed under a standard ULT protocol. Monthly dissolution rates were calculated by simple and compound methods. Correlations with average SU were compared and analyzed. Best-fit regression model was identified. MSU dissolution times were plotted against SU at different endpoints. RESULTS: In 29 tophaceous gout patients, MSU volume reduced from baseline 10.94 ± 10.59 cm3 to 2.87 ± 5.27 cm3 on follow-up (p = .00). Dissolution rate had a stronger correlation with SU if calculated by compound method (Pearson's correlation coefficient r= -0.77, p = .00) and was independent of baseline MSU load. The ensuing dissolution model was logarithmic and explained real-life scenarios. When SU > 0.43 mmol/l, dissolution time approached infinity. It improved to 10-19 months at SU = 0.24 mmol/l. When SU approximated zero (as with pegloticase), dissolution flattened and still took 4-8 months. CONCLUSION: MSU dissolution is better described as a logarithmic function of SU, which explains, predicts, and facilitates understanding of the dissolution process.

Multifunctional Artificial Artery from Direct 3D Printing with Built-In Ferroelectricity and Tissue-Matching Modulus for Real-Time Sensing and Occlusion Monitoring.

Treating vascular grafts failure requires complex surgery procedures and is associated with high risks. A real-time monitoring vascular system enables quick and reliable identification of complications and initiates safer treatments early. Here, an electric fieldassisted 3D printing technology is developed to fabricate in situ-poled ferroelectric artificial arteries that offer battery-free real-time blood pressure sensing and occlusion monitoring capability. The functional artery architecture is made possible by the development of a ferroelectric biocomposite which can be quickly polarized during printing and reshaped into devised objects. The synergistic effect from the potassium sodium niobite particles and the polyvinylidene fluoride polymer matrix yields a superb piezoelectric performance (bulk-scale d 33 > 12 pC N-1). The sinusoidal architecture brings the mechanical modulus close to the level of blood vessels. The desired piezoelectric and mechanical properties of the artificial artery provide an excellent sensitivity to pressure change (0.306 mV mmHg-1, R 2 > 0.99) within the range of human blood pressure (11.25-225.00 mmHg). The high pressure sensitivity and the ability to detect subtle vessel motion pattern change enable early detection of partial occlusion (e.g., thrombosis), allowing for preventing grafts failure. This work demonstrates a promising strategy of incorporating multifunctionality to artificial biological systems for smart healthcare systems.

Degradable Piezoelectric Biomaterials for Wearable and Implantable Bioelectronics.

Current bioelectronics are facing a paradigm shift from old-fashioned unrecyclable materials to green and degradable functional materials with desired biocompatibility. As an essential electromechanical coupling component in many bioelectronics, new piezoelectric materials are being developed with biodegradability, as well as desired mechanical and electromechanical properties for the next generation implantable and wearable bioelectronics. In this review, we provide an overview of the major advancements in biodegradable piezoelectric materials. Different natural (such as peptide, amino acids, proteins, cellulose, chitin, silk, collagen, and M13 phage) and synthetic piezoelectric materials (such as polylactic acid) are discussed to reveal the underlying electromechanical coupling mechanism at the molecular level, together with typical approaches to the alignment of orientation and polarization to boost their electromechanical performance. Meanwhile, in vivo and in vitro degradation manners of those piezoelectric materials are summarized and compared. Representative developments of typical electronic prototypes leveraging these materials are also discussed. At last, challenges toward practical applications are pointed out together with potential research opportunities that might be critical in this new materials research area.

Emotion dysregulation between mothers, fathers, and adolescents: Implications for adolescents' internalizing problems.

INTRODUCTION: The present study calls attention to the longitudinal relations between mothers', fathers', and adolescents' emotion dysregulation and adolescents' internalizing problems. To this end, we tested the associations between family members' emotion dysregulation and adolescents' internalizing problems over time. METHODS: Over a 12-month period, 386 Chinese families from Hong Kong involving mothers, fathers, and adolescent children (children at 12-17 years of age; boys = 185, girls = 201) completed a set of questionnaires twice. RESULTS: Multi-group path analysis revealed unidirectional effects of mothers' emotion dysregulation on fathers' and adolescents' emotion dysregulation over time. Adolescents' emotion dysregulation was also related to their subsequent internalizing problems. The associations did not differ as a function of adolescents' gender. CONCLUSION: The present findings underscore the significance of mothers' emotion dysregulation on fathers' and adolescents' emotion dysregulation. As a risk factor, adolescents' emotion dysregulation was also predictive of their internalizing problems 12 months later. Taken together, this study serves to inform prevention and intervention efforts in promoting emotion regulation as a family asset associated with fewer adolescents' internalizing problems.

Comparison of city-level carbon footprint evaluation by applying single- and multi-regional input-output tables.

City-level carbon footprint has been recognized as a useful measure of anthropogenic impact on climate change associated with citizens' activities within the administrative boundary. Although the promotion of consumer responsibility suggests rethinking urban indirect emissions, the detailed methodology is far from satisfactory for realistic applications. Due to the lack of multi-regional input-output tables for most cities, there is a wide application of single regional input-output tables. However, there still lacks further discussion on if there will be an obvious evaluation bias by applying city-level single-regional tables rather than multi-regional ones. To visualize the table coverage on its application consequence, both single- and multi-regional input-output tables were employed to compare disparities in the carbon footprint accounting in the case of Tokyo, Japan. Our analysis shows that the gap of emissions driven by Tokyo's final demand between single- and multi-regional input-output tables was considerably large. Furthermore, the results of multi-regional table were found to be 8.11 MtC higher for coal-generated emissions, 7.83 MtC for crude oil-generated emissions and 2.90 MtC for natural gas-generated emissions than those of the single-regional table. The largest deviation in emissions accounting was observed in the power, gas and heating supply sector, the construction sector and the private service sector. The gap between these two input-output tables was notable for all three types of fossil fuels (coal, crude oil and natural gas). These indicated that coal-generated emissions have been largely ignored by single-regional input-output table. The study highlighted the difference of carbon footprint accounting between these two types of input-output tables. Our findings are intended to assist policymakers and scholars in pinpointing and reallocating sectors that are likely to yield severely biased evaluation of emissions embodied in trade when a multi-regional table is not available.

A factor-based bottom-up approach for the long-term electricity consumption estimation in the Japanese residential sector.

Recent years, the energy consumption and carbon emissions released from the residential sector have increased rapidly due to the improvement of living standards. Japan, as one of the most developed countries worldwide, is found to be the fourth largest CO2 emitter in the world. Meanwhile, Japan is currently promoting social electrification from varied aspects. And this action further brings the household residential consumption to the vital place for overall energy conservation and emission reduction plans. Although electricity consumption and prediction analysis have been widely discussed. However, previous studies mainly focused on the estimation and analysis of energy consumption at the national level, without enough discussion from prefecture-level insights. To bridge this knowledge gap, this study established a factor-based bottom-up model to estimate the electricity consumption and carbon emissions during the 2015-2040 periods in the Japanese residential sector, considering the prefectural characteristics including per capita gross domestic product, population size, household size, residential floor space area, lifestyle, weather condition, and transition effect of appliance in the future. Nine scenarios that combine three levels of household size and three levels of growth of per capita gross domestic product are taken into account to estimate the electricity consumption for space heating and cooling, water heating, cooking, and appliances. Results indicate that the total residential electricity consumption will reach a peak during 2020s. The total carbon emissions will keep decreasing by 51.14-72.16 Mt between 2015 and 2040. Based on the results of this paper, policy recommendations are given for the Japanese government.

[Evaluation of taste changes of Scutellariae Radix before and after wine-frying based on electronic ongue technology and its application in identification of Scutellariae Radix pieces].

Scutellariae Radix(Huangqin) is a well-known traditional Chinese medicine(TCM) used for the treatment of clearing heat in clinical application. It is bitter-cold by using directly, but the bitter-cold property can be relieved after wine-frying. The study of taste changes before and after wine-frying of Scutellariae Radix is of great significance in identifying Scutellariae Radix and wine-processed Scutellariae Radix and clarifying the traditional theory of wine-processing. In this experiment, 10 batches of Scutellariae Radix and wine-processed Scutellariae Radix were prepared. The contents of 5 flavonoids were determined by high performance liquid chromatography(HPLC), and principal component analysis(PCA) was performed with 5 flavonoids as variables. As a result, the contents were different in different batches of Scutellariae Radix, but Scutellariae Radix and wine-processed Scutellariae Radix could not be distinguished. Five sensory attributes(sour, salty, fresh, sweet, and bitter) were evaluated by artificial tasting, and the response values of 7 sensors(AHS, AHS, PKS, CTS, NMS, CPS, ANS, SCS) representing the taste of pieces were detected by electronic tongue. The correlation between sensory evaluation and response values of the electronic tongue were analyzed, and the results showed that the sensory evaluation of sour, salty, fresh, sweet, bitter and AHS, CTS, NMS, ANS, SCS sensors had different degrees of correlation, indicating that the electronic tongue technology can be used as an alternative to artificial taste and can serve as a means for quantifying the taste, and it can be used to evaluate the taste of TCM pieces. The taste method was used to analyze the response values of the electronic tongue, and the results showed that the bitterness of wine-processed Scutellariae Radix decreased and the salty taste increased. PCA was used to analyze taste changes before and after wine-processed Scutellariae Radix, and the results showed that taste differences between 2 pieces were divided into 2 categories. PCA loading scattering plots showed that response of saltiness and bitterness were the major factors to affect overall taste in Scutellariae Radix and wine-processed Scutellariae Radix. Based on electronic tongue response values, the Fisher discriminant model for Scutellariae Radix and wine-processed Scutellariae Radix was established, which showed that it could effectively discriminate them with a recognition rate of 100%. The experimental results showed that the electronic tongue combined with multivariate statistical analysis can be used to evaluate taste of TCM, at the same time, it could provide a fast and simple method for identifying different processed products.

Circulating obesity-driven biomarkers are associated with risk of clear cell renal cell carcinoma: a two-stage, case-control study.

Obesity is one of modifiable risk factors for clear cell renal cell cancer (ccRCC). We aim to identify the association between obesity-driven biomarkers and ccRCC risk. This is a retrospective, two-phase, case-control study involving 682 cases and 733 controls. Obesity-driven biomarkers [gastric inhibitory polypeptide (GIP), C-peptide, insulin, resistin, adipsin, peptide YY, pancreatic polypeptide, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor-1, monocyte chemoattractant protein 1, lipocalin2, leptin, adiponectin] were measured using the Milliplex method. Multivariate logistic regression was used to assess the associations between biomarkers and ccRCC risk. Results revealed that GIP, C-peptide, IL-6 and TNF-α levels were consistently distinct between cases and controls. These markers were significantly associated with ccRCC risk in both phases (except C-peptide). In the combined population, compared with individuals with low levels of the biomarkers, individuals with high level of GIP [odds ratio (OR) = 0.52, 95% confidence interval (CI): 0.40-0.67] had lower risk, whereas individuals with high levels of C-peptide (OR = 1.46, 95% CI: 1.15-1.87), IL-6 (OR = 2.20, 95% CI: 1.50-3.22), TNF-α (OR = 1.90, 95% CI: 1.49-2.43) had significantly higher risk. Stratified analysis showed consistent associations with ccRCC risk in most subgroups (P < 0.05). The risk score based on the IL-6, TNF-α and GIP was positively associated with ccRCC risk in a dose-response manner (P for trend = 2.18E-13). Data from The Cancer Genome Atlas indicate that insulin signaling, IL-6 signaling and TNF-α signaling were enhanced in tumors. Collectively, our study demonstrates the integrative effect of insulin resistance and inflammation in ccRCC development, which may elucidate the basis of association between obesity and carcinogenesis. Further confirmation in prospective cohort studies are warranted for clinical applications in prevention and precision medicine of ccRCC.

Establishing the functional connectivity of the frontotemporal network in pre-attentive change detection with Transcranial Magnetic Stimulation and event-related optical signal.

Current theories of pre-attentive deviant detection postulate that before the Superior Temporal Cortex (STC) detects a change, the Inferior Frontal Cortex (IFC) engages in stimulus analysis, which is particularly critical for ambiguous deviations (e.g., deviant preceded by a short train of standards). These theories rest on the assumption that IFC and STC are functionally connected, which has only been supported by correlational brain imaging studies. We examined this functional connectivity assumption by applying Transcranial Magnetic Stimulation (TMS) to disrupt IFC function, while measuring the later STC mismatch response with the event-related optical signal (EROS). EROS can localize brain activity in both spatial and temporal dimensions via measurement of optical property changes associated with neuronal activity, and is inert to the electromagnetic interference produced by TMS. Specifically, the STC mismatch response at 120-180 ms elicited by a deviant preceded by a short standard train when IFC TMS was applied at 80 ms was compared with the STC mismatch responses in temporal control (TMS with 200 ms delay), spatial control (sham TMS at vertex), auditory control (TMS pulse noise only), and cognitive control (deviant preceded by a long standard train) conditions. The STC mismatch response to deviants preceded by the short train was abolished by TMS of the IFC at 80 ms, while the STC responses remained intact in all other control conditions. These results confirm the involvement of the IFC in the STC mismatch response and support a functional connection between IFC and STC.

D-chiro-inositol effectively attenuates cholestasis in bile duct ligated rats by improving bile acid secretion and attenuating oxidative stress.

Cholestatic liver diseases are important causes of liver cirrhosis and liver transplantation, but few drugs are available for treatment. D-chiro-inositol (DCI), an isomer of inositol found in many Leguminosae plants and in animal viscera, is used clinically for the treatment of polycystic ovary syndrome (PCOS) and diabetes mellitus. In this study, we investigated whether DCI exerted an anti-cholestatic effect and its underlying mechanisms. A cholestatic rat model was established via bile duct ligation (BDL). After the surgery, the rats were given DCI (150 mg·kg-1·d-1) in drinking water for 2 weeks. Oral administration of DCI significantly decreased the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and attenuated bile duct proliferation, parenchymal necrosis and fibrosis in BDL rats. Furthermore, DCI treatment significantly increased the serum and bile levels of total bile acid (TBA), and decreased TBA levels in the liver. Moreover, DCI treatment significantly increased expression of the genes encoding bile acid transporters BSEP (Abcb11) and MRP2 (Abcc2) in liver tissues. DCI treatment also markedly decreased hepatic CD68 and NF-kappaB (NF-κB) levels, significantly decreased the serum and hepatic MDA levels, markedly increased superoxide dismutase activity in both serum and liver tissues. Using whole-genome oligonucleotide microarray, we revealed that DCI treatment altered the expression profiles of oxidation reduction-related genes in liver tissues. Collectively, DCI effectively attenuates BDL-induced hepatic bile acid accumulation and decreases the severity of injury and fibrosis by improving bile acid secretion, repressing inflammation and decreasing oxidative stress. The results suggest that DCI might be beneficial for patients with cholestatic disorders.