Astragaloside IV Protects Against Podocyte Injury by Upregulating Mitophagy via the Mfn2/Pink1/Parkin Axis.

BACKGROUND: Podocyte injury is the most important pathological hallmark of kidney diseases. Autophagy is a critical factor that involves podocyte injury. Here, we sought to determine whether Astragaloside IV (AS-IV) was able to improve renal function and reverse podocyte injury through the regulation of autophagy. METHODS: Using the Adriamycin (ADR) mice model, cultured immortalized mouse podocytes were exposed to AS-IV. Western blotting, immunofluorescence, and histochemistry were used to analyze markers of autophagy, mitochondrial dysfunction, podocyte apoptosis, and glomerulopathy in the progression of focal segmental glomerular sclerosis. RESULTS: We observed that AS-IV can inhibit podocyte apoptosis, increased reactive oxygen species (ROS) generation, mitochondrial fragmentation, and dysfunction by inducing the Mfn2/Pink1/Parkin mitophagy pathway both in vivo and in vitro. Overexpression of Mfn2 reduced puromycin aminonucleoside (PAN)-induced podocyte injury, while downregulation of Mfn2 expression limited the renal protective effect of AS-IV by regulating mitophagy. CONCLUSION: AS-IV ameliorates renal function and renal pathological changes in ADR mice and inhibits PAN-induced podocyte injury by directly enhancing Mfn2/Pink1/Parkin-associated autophagy.

Haemoglobin, albumin, lymphocyte, and platelet score as an independent predictor for renal prognosis in IgA nephropathy.

Objective: The haemoglobin, albumin, lymphocyte, and platelet (HALP) score, a convenient and composite laboratory biomarker, can reflect inflammation and systemic nutritional status. This study was performed to investigate the effect of the HALP score on the prognosis of patients with IgA nephropathy (IgAN). Methods: This is a retrospective single centre study that enrolled 895 biopsy-confirmed IgAN patients from June 2019 to June 2022 who were followed for more than 1 year. Kaplan-Meier curves and Cox regression analyses were performed to determine the relationship between HALP and adverse outcomes. The restricted cubic splines was used to identify the possible associations. The optimal cut-off value of HALP for renal poor outcome was identified by the area under the receiver operating characteristic curve (AUC). Results: A total of 895 patients finally participated in the study and were divided into three groups (tertial 1-3) according to the baseline HALP score. More severe clinicopathologic features were observed in the lower HALP group, and Kaplan-Meier analysis showed patients in tertial 1 had a higher risk of kidney failure than the other groups (log-rank=11.02, P= 0.004). Multivariate Cox regression revealed that HALP score was an independent risk factor for renal prognosis in IgAN (adjusted HR: 0.967, 95% CI: 0.945-0.990, P = 0.006). The results of subgroup analysis suggested that HALP was more important in patients under the age of 50, BMI ≤ 23.9 and eGFR ≤ 90 mL/min/1.73 m2. The best cut-off HALP for renal survival was 38.83, sensitivity 72.1%, and specificity 55.9% (AUC: 0.662). Patients were further grouped according to HALP cut-off values and propensity matched. Multivariate Cox regression analysis revealed that HALP remained an independent predictor of IgAN in the matched cohort (HR 0.222, CI: 0.084-0.588, P=0.002). Conclusion: HALP is a novel and potent composite parameter to predict kidney outcome in patients with IgAN.

S100 proteins in head and neck squamous cell carcinoma (Review).

The most common tumor affecting the head and neck is head and neck squamous cell carcinoma (HNSCC). The characteristics of HNSCC include a rapid onset, a lack of early diagnosis, drug resistance, relapse and systemic adverse effects, leading to inadequate prevention, diagnosis and treatment. Notably, previous research suggests that there is an association between S100 proteins and HNSCC. S100A8, S100A9 and S100A14 interfere with tumor cell proliferation by blocking the cell cycle. The present review discusses this association. S100A4 enhances cancer stem cell properties, and interacts with actin and tropomyosin to promote tumor cell migration. S100A1, S100A8, S100A9, S100A10, S100A14 and S100P are involved in the initiation and progression of HNSCC via Hippo, nuclear factor κB, phosphatidylinositol kinase/protein kinase B/mammalian target of rapamycin and other signaling pathways. In addition, certain long non-coding RNAs and microRNAs are involved in regulating the expression of S100 proteins in HNSCC. Reducing the expression of certain members of the S100 protein family may enhance the chemosensitivity of HNSCC. Collectively, it is suggested that S100 proteins may function as markers and targets for the prevention, diagnosis and treatment of HNSCC.

Fangchinoline inhibits non-small cell lung cancer metastasis by reversing epithelial-mesenchymal transition and suppressing the cytosolic ROS-related Akt-mTOR signaling pathway.

Few drugs alleviate non-small cell lung cancer (NSCLC) metastasis effectively. Small molecular screening demonstrated that fangchinoline (Fan) reversed epithelial-mesenchymal transition (EMT) in NSCLC cells, inhibiting cell invasion and migration. RNA sequencing (RNA-seq) of Fan-treated NSCLC cells revealed that Fan potently quenched the NADP+ metabolic process. Molecular docking analysis revealed that Fan directly and specifically targeted NOX4. NOX4 was associated with poor prognosis in NSCLC in both The Cancer Genome Atlas (TCGA) and Hong Kong cohorts. In mitochondrial DNA-depleted ρ0 NSCLC cells, Fan decreased cytosolic reactive oxygen species (ROS) to inhibit the Akt-mTOR signaling pathway by directly promoting NOX4 degradation. In TCGA and Hong Kong cohorts, NOX4 upregulation acted as a driver event as it positively correlated with metastasis and oxidative stress. Single-cell RNA-seq indicated that NOX4 was overexpressed, especially in cancer cells, cancer stem cells, and endothelial cells. In mice, Fan significantly impeded subcutaneous xenograft formation and reduced metastatic nodule numbers in mouse lung and liver. Drug sensitivity testing demonstrated that Fan suppressed patient-derived organoid growth dose-dependently. Fan is a potent small molecule for alleviating NSCLC metastasis by directly targeting NOX4 and is a potential novel therapeutic agent.

Causal Relationships Between Social Isolation and Osteoarthritis: A Mendelian Randomization Study in European Population.

OBJECTIVE: We aimed to investigate the causal relationships between social isolation and osteoarthritis. METHODS: Publicly available genome-wide association study (GWAS) summary statistics of social isolation and osteoarthritis in European population were obtained from the Neale lab Consortium and the Medical Research Council-Integrative Epidemiology Unit (MRC-IEU) consortium, respectively. Single nucleotide polymorphisms (SNPs) associated with the traits were identified by P < 5×10-8 and linkage disequilibrium r2 < 0.1. Three Mendelian randomization (MR) methods including the inverse-variance weighted (IVW) method, weighted median estimator, and MR-Egger regression were used to assess the potential causal effect of social isolation on osteoarthritis and the potential causal effect of osteoarthritis on social isolation. Leave-one-out analysis and test of directional horizontal pleiotropy via MR-Egger regression were performed as sensitivity analyses. RESULTS: When evaluating the causal effect of social isolation on osteoarthritis, five SNPs (rs12364432, rs13291079, rs2352075, rs4958586, rs599550) significantly associated with social isolation were studied as instruments, and social isolation was found to be causally associated with increased risk of osteoarthritis (odds ratio [OR] 1.197 (95% confidence interval (CI) 1.096-1.308) estimated by the IVW method). When evaluating the causal effect of osteoarthritis on social isolation, six SNPs (rs10405617, rs12133235, rs13107325, rs2290573, rs3771501, rs75621460) significantly associated with osteoarthritis were studied as instruments but no causal effect of osteoarthritis on social isolation was found (OR 1.104 (95% CI 0.887-1.375) estimated by the IVW method). Consistent causal relationships were observed when estimated by the weighted median estimator and MR-Egger regression. Leave-one-out analysis and test of directional horizontal pleiotropy suggested the robustness of the above findings. CONCLUSION: Social isolation is causally associated with osteoarthritis, and further work is needed to investigate the potential mechanisms.

Interlaminar Fracture Behavior of Carbon Fiber/Polyimide Composites Toughened by Interleaving Thermoplastic Polyimide Fiber Veils.

Carbon fiber reinforced thermosetting polyimide (CF/TSPI) composites were interleaved with thermally stable thermoplastic polyimide (TPPI) fiber veils in order to improve the interlaminar fracture toughness without sacrificing the heat resistance. Both of the mode I and mode II interlaminar fracture toughness (GIC and GIIC) for the untoughened laminate and TPPI fiber veils interleaved laminates were characterized by the double cantilever beam (DCB) test and end notch flexure (ENF) test, respectively. It is found that the TPPI fiber veils interleaved laminates exhibit extremely increased fracture toughness than the untoughened one. Moreover, the areal density of TPPI greatly affected the fracture toughness of laminates. A maximum improvement up to 179% and 132% on GIC and GIIC is obtained for 15 gsm fiber veils interleaved laminate, which contributes to the existence of bicontinuous TPPI/TSPI structure in the interlayer according to the fractography analysis. The interlaminar fracture behavior at elevated temperatures for 15 gsm fiber veils interleaved laminate were also investigated. The results indicated that the introduction of thermally stable TPPI fiber veils could enhance the fracture toughness of CF/TSPI composites by exceeding 200% as compared to the untoughened one even as tested at 250 °C.

The Causal Relationship Between Body Mass Index and the Risk of Osteoarthritis.

OBJECTIVE: The study aimed to explore the causal effect of body mass index (BMI) on osteoarthritis. METHODS: The genome-wide association data of BMI and osteoarthritis were obtained via the Mendelian randomization (MR)-base platform. Single nucleotide polymorphisms (SNPs) significantly associated with BMI were identified and used as instrumental variables, and the causal relationship between BMI and osteoarthritis was examined using the two-sample MR research method. Three statistical methods including inverse-variance weighted (IVW) method, weighted median estimator, and MR-Egger regression were employed. RESULTS: A total of 79 SNPs significantly associated with BMI were identified in the study (P<5×10-8; linkage disequilibrium r2 <0.1). Consistent association between BMI and osteoarthritis was observed when evaluated by different methods (IVW: odds ratio (OR) 1.028, 95% confidence interval (CI) 1.021-1.036; weighted median estimator: OR 1.028, 95% CI 1.019-1.037; MR-Egger regression: OR 1.028, 95% CI 1.009-1.046), which suggests that BMI is positively associated with increased risk of osteoarthritis. There was no evidence that the observed causal effect between BMI and the risk of osteoarthritis was affected by genetic pleiotropy (MR-Egger intercept 1.3×10-5, P=0.959). CONCLUSION: The MR analysis provided the strong evidence to indicate that BMI might be causally associated with the risk of osteoarthritis.

Comparing the Cell Dynamics of Tree-Ring Formation Observed in Microcores and as Predicted by the Vaganov-Shashkin Model.

New insights into the intra-annual dynamics of tree-ring formation can improve our understanding of tree-growth response to environmental conditions at high-resolution time scales. Obtaining this information requires, however, a weekly monitoring of wood formation, sampling that is extremely time-intensive and scarcely feasible over vast areas. Estimating the timing of cambial and xylem differentiation by modeling thus represents an interesting alternative for obtaining this important information by other means. Temporal dynamics of cambial divisions can be extracted from the daily tree-ring growth rate computed by the Vaganov-Shashkin (VS) simulation model, assuming that cell production is tightly linked to tree-ring growth. Nonetheless, these predictions have yet to be compared with direct observations of wood development, i.e., via microcoring, over a long time span. We tested the performance of the VS model by comparing the observed and predicted timing of wood formation in black spruce [Picea mariana (Mill.)]. We obtained microcores over 15 years at 5 sites along a latitudinal gradient in Quebec (Canada). The measured variables included cell size and the timing of cell production and differentiation. We calibrated the VS model using daily temperature and precipitation recorded by weather stations located on each site. The predicted and observed timing of cambial and enlarging cells were highly correlated (R 2 = 0.8); nonetheless, we detected a systematic overestimation in the predicted timing of cambial cells, with predictions delayed by 1-20 days compared with observations. The growth rate of cell diameter was correlated with the predicted growth rate assigned to each cambial cell, confirming that cell diameter developmental dynamics have the potential to be inferred by the tree-ring growth curve of the VS model. Model performances decrease substantially in estimating the end of wood formation. The systematic errors suggest that the actual relationships implemented in the model are unable to explain the phenological events in autumn. The mismatch between the observed and predicted timing of wood formation in black spruce within our study area can be reduced by better adapting the VS model to wet sites, a context for which this model has been rarely used.

High Thermally Stable and Melt Processable Polyimide Resins Based on Phenylethynyl-Terminated Oligoimides Containing Siloxane Structure.

A series of 4-phenylethnylphthalic anhydride (PEPA)-terminated oligoimides were prepared by co-oligomerizing isomeric dianhydrides, i.e., 2,3,3',4'-biphenyltetracarboxylic dianhydride (a-BPDA), 2,3,3',4'-benzophenonetetracarboxylic dianhydride (a-BTDA) or 2,3,3',4'-diphenylethertetracarboxylic dianhydride (a-ODPA), with diamines mixture of bis(4-aminophenoxy)dimethyl silane (APDS) and 2,2'-bis(trifluoromethyl) benzidine (TFDB). The effects of siloxane content and dianhydride structure on the rheological properties of these oligoimides and thermal stability of the corresponding cured polyimide resins were investigated. The results indicated that the introduction of the siloxane structure improved the melt processability of the oligoimides, while the thermal stability of the cured polyimide resins reduced. The oligoimide derived from a-ODPA revealed better melt processability and melt stability due to the existence of a flexible dianhydride structure. The oligoimide PIS-O10 derived from a-ODPA gave the lowest minimum melt viscosity of 0.09 Pa·s at 333 °C and showed the excellent melt stability at 260 °C for 2 h with the melt viscosity in the range of 0.69-1.63 Pa·s. It is also noted that the thermal stability of these resins can be further enhanced by postcuring at 400-450 °C, which is attributed to the almost complete chemical crosslinking of the phenyethynyl combined with oxidative crosslinking of siloxane. The PIS-T10 and PIS-O10 resins that were based on a-BTDA and a-ODPA, respectively, even showed a glass transition temperature over 550 °C after postcuring at 450 °C for 1 h.

The Initiation of Swallowing Can Indicate the Prognosis of Disorders of Consciousness: A Self-Controlled Study.

Objective: To detect the initiation of swallowing in patients with disorders of consciousness (DOC) as well as the relationship between the initiation of swallowing and the prognosis of DOC patients. Methods: Nineteen DOC patients were included in this study, and a self-controlled trial compared five different stimuli. The five different stimuli were as follows: (1) one command, as recommended by the Coma Recovery Scale-Revised (CRS-R), which was "open your mouth"; (2) placing a spoon in front of the patient's mouth without a command; (3) placing a spoon filled with water in front of the patient's mouth without a command; (4) one command-"there is a spoon; open your mouth"-with a spoon in front of the patient's mouth; (5) one command, "there is a spoon with water; open your mouth," with a spoon filled with water in front of the patient's mouth. All 19 patients were given these five stimuli randomly, and any one of the commands was presented four times to a patient, one at a time, at 15-s intervals. The sensitivity and specificity of the initiation of swallowing in detecting conscious awareness were determined. Results: None of the patients responded to the first four stimuli. However, six patients showed initiated swallowing toward the fifth stimulus. Among those six, five patients showed improvement in their consciousness state 6 months later. The sensitivity and specificity of the initiation of swallowing for DOC patients was 83.33% [95% CIs (36%, 100%)] and 92.31% [95% CIs (64%, 100%)], respectively. Conclusions: The initiation of swallowing can be an early indication of conscious behavior and can likely provide evidence of conscious awareness. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03508336; Date of registration: 2018/4/16.

Validation of the Chinese version of the Coma Recovery Scale-Revised (CRS-R).

PRIMARY OBJECTIVE: This study aims to validate the Chinese version of the Coma Recovery Scale-Revised (CRS-R). METHODS: One hundred sixty-nine patients were assessed with both the CRS-R and the Glasgow Coma Scale (GCS), diagnosed as being in unresponsive wakefulness syndrome (UWS, formerly known as vegetative state), minimally conscious state (MCS), or emergence from MCS (EMCS). A subgroup of 50 patients has been assessed twice by the same rater, within 24 h. Patient outcome was documented six months after assessment. RESULTS: The internal consistency for the CRS-R total score was excellent (Cronbach's α = 0.84). Good test-retest reliability was obtained for CRS-R total score and subscale scores (intra-class correlation coefficient [ICC] = 0.87 and ICC = 0.66-0.84, respectively). Inter-rater reliability was high (ICC = 0.719; p < 0.01). Concurrent validity was good between CRS-R total scale and GCS total scale. Diagnostic validity was excellent compared with GCS (emerged from UWS: 24%; emerged from MCS: 28%). When considering patient outcome, diagnostic validity was good. In addition, false-positive rates have been detected for both diagnoses. CONCLUSION: The Chinese version of the CRS-R is a reliable and sensitive tool and can discriminate patients in UWS, MCS, and EMCS successfully.

Highly sensitive fluorometric determination of thrombin by on-chip signal amplification initiated by terminal deoxynucleotidyl transferase.

The article describes an on-chip amplification scheme initiated by a terminal deoxynucleotidyl transferase (TdT) for highly sensitive fluorometric determination of protein. Two thrombin-binding aptamers were designed to capture thrombin as they can form a sandwich structure for improved specificity. An amino-modified aptamer (TBA29) was first immobilized on a silicon chip. After capture of thrombin, a second aptamer (TBA15) was conjugated to the second binding site of thrombin. The 3'-terminal of aptamer TBA15 is exposed on the chip surface, and then fluorescein-labeled 12-dATP associates to the 3'-terminal with the help of TdT. This results in signal amplification, and eventually leads to highly sensitive detection. Under optimal conditions, fluorescence intensity is linearly related to the logarithm of thrombin concentration in the range of 100 fM - 0.1 µM, and the detection limit is as low as 2.0 fM. The assay is sensitive and selective even over potentially interfering proteins and in the presence of human serum. Graphical abstract Schematic strategy for thrombin detection. Two thrombin-binding aptamers were designed to capture thrombin to form a sandwich structure for improved specificity. The protein detection is based on TdT initiated on-chip fluorescent amplification.

Metal-to-Ligand Charge-Transfer-based Visual Detection of Alkaline Phosphatase Activity.

The ability to directly detect alkaline phosphatase (ALP) activity in undiluted serum samples is of great importance for clinical diagnosis. In this work, we report the use of the distinctive metal-to-ligand charge-transfer (MLCT) absorption properties of the Cu(BCA)2+ (BCA = bicinchoninic acid) reporter for the visual detection of ALP activity. In the presence of ALP, the substrate ascorbic acid 2-phosphate (AAP) can be enzymatically hydrolyzed to release ascorbic acid (AA), which in turn reduces Cu2+ to Cu+. Subsequently, the complexation of Cu+ with the BCA ligand generates the chromogenic Cu(BCA)2+ reporter, accompanied by a color change of colorless-to-purple of the solution with a sharp absorption band at 562 nm. The underlying MLCT-based mechanism has been demonstrated on the basis of density functional theory (DFT) calculations. Needless of any sequential multistep operations and elaborately designed colorimetric probe, the proposed MLCT-based method allows for a fast and sensitive visual detection of ALP activity within a broad linear range of 20 - 200 mU mL-1 (R2 = 0.999), with a detection limit of 1.25 mU mL-1. The results also indicate that it is highly selective and has great potential for the screening of ALP inhibitors in drug discovery. More importantly, it shows a good analytical performance for the direct detection of the endogenous ALP levels of undiluted human serum samples. Owing to the prominent simplicity and practicability, it is reasonable to conclude that the proposed MLCT-based method has a high application prospect in clinical diagnosis.

Fluorescence quenching based alkaline phosphatase activity detection.

Simple and fast detection of alkaline phosphatase (ALP) activity is of great importance for diagnostic and analytical applications. In this work, we report a turn-off approach for the real-time detection of ALP activity on the basis of the charge transfer induced fluorescence quenching of the Cu(BCDS)22- (BCDS = bathocuproine disulfonate) probe. Initially, ALP can enzymatically hydrolyze the substrate ascorbic acid 2-phosphate to release ascorbic acid (AA). Subsequently, the AA-mediated reduction of the Cu(BCDS)22- probe, which displays an intense photoluminescence band at the wavelength of 402nm, leads to the static quenching of fluorescence of the probe as a result of charge transfer. The underlying mechanism of the fluorescence quenching was demonstrated by quantum mechanical calculations. The Cu(BCDS)22- probe features a large Stokes shift (86nm) and is highly immune to photo bleaching. In addition, this approach is free of elaborately designed fluorescent probes and allows the detection of ALP activity in a real-time manner. Under optimal conditions, it provides a fast and sensitive detection of ALP activity within the dynamic range of 0-220mUmL-1, with a detection limit down to 0.27mUmL-1. Results demonstrate that it is highly selective, and applicable to the screening of ALP inhibitors in drug discovery. More importantly, it shows a good analytical performance for the direct detection of the endogenous ALP levels of undiluted human serum and even whole blood samples. Therefore, the proposed charge transfer based approach has great potential in diagnostic and analytical applications.

Projections for the changes in growing season length of tree-ring formation on the Tibetan Plateau based on CMIP5 model simulations.

The response of the growing season to the ongoing global warming has gained considerable attention. In particular, how and to which extent the growing season will change during this century is essential information for the Tibetan Plateau, where the observed warming trend has exceeded the global mean. In this study, the 1960-2014 mean length of the tree-ring growing season (LOS) on the Tibetan Plateau was derived from results of the Vaganov-Shashkin oscilloscope tree growth model, based on 20 composite study sites and more than 3000 trees. Bootstrap and partial correlations were used to evaluate the most significant climate factors determining the LOS in the study region. Based on this relationship, we predicted the future variability of the LOS under three emission scenarios (Representative Concentration Pathways (RCP) 2.6, 6.0, and 8.5, representing different concentrations of greenhouse gasses) derived from 17 Earth system models participating in the Coupled Model Intercomparison Project Phase 5 (CMIP5). The averaged LOS on the Tibetan Plateau is 103 days during the period 1960-2014, and April-September minimum temperature is the strongest factor controlling the LOS. We detected a general increase in the LOS over the twenty-first century under all the three selected scenarios. By the middle of this century, LOS will extend by about 3 to 4 weeks under the RCPs 2.6 and 6.0, and by more than 1 month (37 days) under the RCP 8.5, relative to the baseline period 1960-2014. From the middle to the end of the twenty-first century, LOS will further extend by about 3 to 4 weeks under the RCPs 6.0 and 8.5, respectively. Under the RCP 2.6 scenario, however, the extension reaches a plateau at around 2050 and about 2 weeks LOS extension. In total, we found an average rate of 2.1, 3.6, and 5.0 days decade-1 for the LOS extension from 2015 to 2100 under the RCPs 2.6, 6.0, and 8.5, respectively. However, such estimated LOS extensions may be offset by other ecological factors that were not included into the growth model. The estimated lengthening of the growing season could substantially affect carbon sequestration and forest productivity on the Tibetan Plateau.

Coenzyme Q10 Prevents the Interleukin-1 Beta Induced Inflammatory Response via Inhibition of MAPK Signaling Pathways in Rat Articular Chondrocytes.

Preclinical Research Osteoarthritis (OA) is a widely prevalent degenerative joint disease that severely impairs the health of the elderly population resulting in a heavy economic burden worldwide. Coenzyme Q10 (CoQ10) has shown anti-inflammatory effects in some diseases. The present study aimed to investigate if CoQ10 would suppress catabolic responses of interleukin (IL)-1ß-induced chondrocytes. Rat chondrocytes were cultured and pretreated with CoQ10, and then stimulated with or without IL-1ß (10 ng/ml). The expression and production of matrix metalloproteinase (MMP)-3, MMP-9, and MMP13 were determined using real-time PCR and Western blotting. CoQ10 suppressed MMP-3, MMP-9, and MMP13 production induced by IL-1ß, and markedly inhibited IL-1ß-induced MAPK pathways in rat chondrocytes. The present study provides insight into potential mechanisms by which CoQ10 protects against degeneration of cartilage in patients with OA, which may lead to new approaches for the treatment of OA.Drug Dev Res 78 : 403-410, 2017. © 2017 Wiley Periodicals, Inc.

New perspective on spring vegetation phenology and global climate change based on Tibetan Plateau tree-ring data.

Phenological responses of vegetation to climate, in particular to the ongoing warming trend, have received much attention. However, divergent results from the analyses of remote sensing data have been obtained for the Tibetan Plateau (TP), the world's largest high-elevation region. This study provides a perspective on vegetation phenology shifts during 1960-2014, gained using an innovative approach based on a well-validated, process-based, tree-ring growth model that is independent of temporal changes in technical properties and image quality of remote sensing products. Twenty composite site chronologies were analyzed, comprising about 3,000 trees from forested areas across the TP. We found that the start of the growing season (SOS) has advanced, on average, by 0.28 d/y over the period 1960-2014. The end of the growing season (EOS) has been delayed, by an estimated 0.33 d/y during 1982-2014. No significant changes in SOS or EOS were observed during 1960-1981. April-June and August-September minimum temperatures are the main climatic drivers for SOS and EOS, respectively. An increase of 1 °C in April-June minimum temperature shifted the dates of xylem phenology by 6 to 7 d, lengthening the period of tree-ring formation. This study extends the chronology of TP phenology farther back in time and reconciles the disparate views on SOS derived from remote sensing data. Scaling up this analysis may improve understanding of climate change effects and related phenological and plant productivity on a global scale.

Metal-to-ligand charge-transfer: Applications to visual detection of ß-galactosidase activity and sandwich immunoassay.

In this work, we report a novel use of the distinctive metal-to-ligand charge-transfer (MLCT) absorption properties of the chromogenic Fe(BPDS)34- (BPDS=bathophenanthroline disulfonic acid) reporter for the visual detection of ß-galactosidase (ß-Gal) activity and sandwich immunoassay. The enzymatic hydrolysis of the substrate p-aminophenyl-ß-D-galactopyranoside can switch on the reduction of Fe3+ to Fe2+ and the subsequent complexation of Fe2+ with the BPDS ligand to generate the Fe(BPDS)34- reporter, leading to the appearance of the intense MLCT absorption band at 535nm and the colorless-to-red color change of the solution. Simply through a single step, the activity of ß-Gal can be sensitively and selectively detected within the dynamic range of 0-220mUmL-1, with a limit of detection (LOD) of 1.69mUmL-1. This approach is applicable for the visual detection of ß-Gal activities in the presence of complex human serum samples. Besides, when integrated with the sandwich immunoassay of carcinoembryonic antigen, a LOD of 1.16ngmL-1 can be achieved. In light of its prominent simplicity and practicality, our MLCT-based approach holds great potential in diagnostic and analytical applications.

Chinese translation of the Coma Recovery Scale-Revised.

BACKGROUND: Misdiagnosis rate is high in patients with disorders of consciousness, potentially leading to an inappropriate clinical management of these patients. Sensitive standardised rating scales offer some protections from these diagnostic errors. In this context, the use of the Coma Recovery Scale-Revised (CRS-R) has strongly been recommended by the American Congress of Rehabilitation Medicine. OBJECTIVE: Here, we present the work that has been performed to translate this important diagnostic tool in Chinese. METHODS: The scale has been translated from its original English version to Chinese by a team of native Chinese speakers in agreement with an expert highly trained in the use of the original version of the CRS-R and, then, back-translated to English by four independent translators blinded to the original version. The resulting translation has been sent to the original author for final approval. RESULTS AND CONCLUSION: The Chinese version of the CRS-R is now available for use in clinical practise. Further investigations will nevertheless be needed in order to show that its psychometric properties are identical to the original English version.