Achieving Dendrite-Free and By-Product-Free Aqueous Zn-Ion Battery Anode via Nicotinic Acid Electrolyte Additive with Molecule-Ion Conversion Mechanism.

The widespread adoption of aqueous Zn ion batteries is hindered by the instability of the Zn anode. Herein, an elegant strategy is proposed to enhance the stability of Zn anode by incorporating nicotinic acid (NA), an additive with a unique molecule-ion conversion mechanism, to optimize the anode/electrolyte interface and the typical ZnSO4 electrolyte system. Experimental characterization and theoretical calculations demonstrate that the NA additive preferentially replaces H2O in the original solvation shell and adsorbs onto the Zn anode surface upon conversion from molecule to ion in the electrolyte environment, thereby suppressing side reactions arising from activated H2O decomposition and stochastic growth of Zn dendrites. Simultaneously, such a molecule-to-ion conversion mechanism may induce preferential deposition of Zn along the (002) plane. Benefiting from it, the Zn||Zn symmetric battery cycles stably for 2500 h at 1 mA cm-2, 1 mAh cm-2. More encouragingly, the Zn||AC full batteries and the Zn||AC full batteries using NA electrolyte and Zn||VO2 full batteries also exhibit excellent performance improvements. This work emphasizes the role of variation in the form of additives (especially weak acid-based additives) in fine-tuning the solvation structure and the anode/electrolyte interface, hopefully enhancing the performance of various aqueous metal batteries.

Inert Group-Containing Electrolyte Additive Enabling Stable Aqueous Zinc-Ion Batteries.

Aqueous zinc ion batteries (AZIBs) are considered promising energy storage devices because of their high theoretical energy density and cost-effectiveness. However, the ongoing side reactions and zinc dendrite growth during cycling limit their practical application. Herein, trisodium methylglycine diacetate (Na3MGDA) additive containing the additional inert group methyl is introduced for Zn anode protection, and the contribution of methyl as an inert group to the Zn anode stability is discussed. Experimental results reveal that the methyl group with various effects enhances the interaction between the polar groups in Na3MGDA and the Zn2+/Zn anode. Thus, the polar carboxylate negative ions in MGDA anions can more easily modify the solvation structure and adsorb on the anode surface in situ to establish a hydrophobic electrical double layer (EDL) layer with steric hindrance effects. Such the EDL layer exhibits a robust selectivity for Zn deposition and a significant inhibition of parasitic reactions. Consequently, the Zn||Zn symmetric battery presents 2375 h at 1 mA cm-2, 1 mAh cm-2, and the Zn||V6O13 full battery provides 91% capacity retention after 1300 cycles at 3 A g-1. This study emphasizes the significant role of inert groups of the additive on the interfacial stability during the plating/stripping of high-performance AZIBs.

Health-related quality of life and subjective well-being among children aged 9-12 years in Shandong Province, China.

PURPOSE: To investigate the health-related quality of life (HRQoL) and subjective well-being (SWB) of children aged 9-12 years in eastern China, and examine concordance within child self-reported and parent proxy-assessed. METHODS: Data was collected from 9 to 12 years old children (including their parents) in Shandong Province in 2018. Participants self-completed a hard-copy questionnaire including Child Health Utility 9D (CHU9D), Pediatric Quality of Life Inventory (PedsQL)™ 4.0 Short Form 15 Generic Core Scales (hereafter the PedsQL™), Student's Life Satisfaction Scale (SLSS), as well as information on socio-demographic characteristics and self-report health status. Spearman's correlation coefficients and the difference between sub-groups were conducted to assess and compare the agreement on HRQoL and SWB instruments. Exploratory factor analysis (EFA) was used to ascertain the number of unique underlying latent factors that were associated with the items covered by the two generic HRQoL and the SWB instruments. The concordance of child self-reported and parent proxy-assessed was analyzed using weighted kappa coefficient and Bland-Altman plots. RESULTS: A total of 810 children and 810 parents were invited to participate in the survey. A valid sample of 799 (98.6%) children and 643 (79.4%) parents completed the questionnaire. The child self-reported mean scores were CHU9D = 0.87, PedsQL™ = 83.47, and SLSS = 30.90, respectively. The parent proxy-assessed mean scores were PedsQL™ = 68.61 and SLSS = 31.23, respectively. The child self-reported PedsQL™ was moderately correlated with the CHU9D (r = 0.52). There was a weak correlation between CHU9D and SLSS (r = 0.27). The EFA result found 3 factors whilst seven SLSS items grouped into a standalone factor (factor 3), and the nine dimensions of CHU9D shared two common factors with the PedsQL™ (factor 1 and factor 2). A low level of concordance was observed across all comparisons and in all domains (weighted kappa < 0.20) between parents and their children. Furthermore, a high level of discordance was observed between child self-reported and father proxy-assessed. CONCLUSIONS: CHU9D and PedsQL™ instruments have a higher agreement in measuring the HRQoL in children. CHU9D/PedsQL™ and SLSS instruments showed a low agreement and EFA result suggested that measuring SWB in children potentially may provide further information, which might be overlooked by using HRQoL instruments exclusively. Concordance of child self-reported and parent proxy-assessed was poor. Overall, mother-child concordance was higher than father-child concordance.

Melt-electrowriting-enabled anisotropic scaffolds loaded with valve interstitial cells for heart valve tissue Engineering.

Tissue engineered heart valves (TEHVs) demonstrates the potential for tissue growth and remodel, offering particular benefit for pediatric patients. A significant challenge in designing functional TEHV lies in replicating the anisotropic mechanical properties of native valve leaflets. To establish a biomimetic TEHV model, we employed melt-electrowriting (MEW) technology to fabricate an anisotropic PCL scaffold. By integrating the anisotropic MEW-PCL scaffold with bioactive hydrogels (GelMA/ChsMA), we successfully crafted an elastic scaffold with tunable mechanical properties closely mirroring the structure and mechanical characteristics of natural heart valves. This scaffold not only supports the growth of valvular interstitial cells (VICs) within a 3D culture but also fosters the remodeling of extracellular matrix of VICs. The in vitro experiments demonstrated that the introduction of ChsMA improved the hemocompatibility and endothelialization of TEHV scaffold. The in vivo experiments revealed that, compared to their non-hydrogel counterparts, the PCL-GelMA/ChsMA scaffold, when implanted into SD rats, significantly suppressed immune reactions and calcification. In comparison with the PCL scaffold, the PCL-GelMA/ChsMA scaffold exhibited higher bioactivity and superior biocompatibility. The amalgamation of MEW technology and biomimetic design approaches provides a new paradigm for manufacturing scaffolds with highly controllable microstructures, biocompatibility, and anisotropic mechanical properties required for the fabrication of TEHVs.

Long-term decrease in Asian monsoon rainfall and abrupt climate change events over the past 6,700 years.

Asian summer monsoon (ASM) variability and its long-term ecological and societal impacts extending back to Neolithic times are poorly understood due to a lack of high-resolution climate proxy data. Here, we present a precisely dated and well-calibrated tree-ring stable isotope chronology from the Tibetan Plateau with 1- to 5-y resolution that reflects high- to low-frequency ASM variability from 4680 BCE to 2011 CE. Superimposed on a persistent drying trend since the mid-Holocene, a rapid decrease in moisture availability between ∼2000 and ∼1500 BCE caused a dry hydroclimatic regime from ∼1675 to ∼1185 BCE, with mean precipitation estimated at 42 ± 4% and 5 ± 2% lower than during the mid-Holocene and the instrumental period, respectively. This second-millennium-BCE megadrought marks the mid-to late Holocene transition, during which regional forests declined and enhanced aeolian activity affected northern Chinese ecosystems. We argue that this abrupt aridification starting ∼2000 BCE contributed to the shift of Neolithic cultures in northern China and likely triggered human migration and societal transformation.

The Effectiveness and Safety Analysis of Duloxetine in Treating Comorbid Depression in Parkinson's Disease: A Retrospective Study.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by both motor and non-motor symptoms, including depression, which significantly impacts the quality of life of affected individuals. This study aims to investigate the real-world effectiveness and safety of duloxetine in treating comorbid depression in patients with Parkinson's disease and to compare its outcomes with traditional treatment approaches. METHODS: This study included adult patients diagnosed with Parkinson's disease combined with depression from December 2020 to December 2023. Based on the use of duloxetine, the cohort was divided into a traditional treatment group and a duloxetine group (traditional treatment combined with duloxetine). Patients with incomplete medical records, concurrent antidepressant therapy, or major psychiatric or neurological disorders were excluded. Retrospective data, including demographic information, treatment adherence, and various assessment scores, were collected from medical records by trained research staff. RESULTS: In total, 106 patients were analyzed, with 50 patients receiving traditional treatment and 56 patients receiving duloxetine. The duloxetine group exhibited significantly lower scores than the traditional treatment group in the Unified PD Rating Scale (p = 0.015), Hamilton Depression Rating Scale (p = 0.013), Beck Depression Inventory (p = 0.031), Parkinson's disease Questionnaire-39 (p = 0.006), and Clinical Global Impression-Improvement (p < 0.001) scores. In motor function assessment, the duloxetine group demonstrated improvements in kinetic tremor scores (p = 0.017), gait speed (p < 0.001), Timed Up and Go Test performance (p < 0.001), dyskinesia severity (p = 0.017), and rigidity (p = 0.019) compared to the traditional treatment group. Additionally, the duloxetine group exhibited better cognitive function across various assessments, including the Symbol Digit Modalities Test (p = 0.024), Stroop Color-Word Test (p = 0.048), and Montreal Cognitive Assessment (p = 0.024). CONCLUSION: Duloxetine is associated with superior efficacy in improving motor and non-motor symptoms, overall clinical status, and cognitive function. These findings support the potential utility of duloxetine as a comprehensive treatment option for comorbid depression in Parkinson's disease.

FePSe3 -Nanosheets-Integrated Cryogenic-3D-Printed Multifunctional Calcium Phosphate Scaffolds for Synergistic Therapy of Osteosarcoma.

Clinical treatment of osteosarcoma encounters great challenges of postsurgical tumor recurrence and extensive bone defect. To develop an advanced artificial bone substitute that can achieve synergistic bone regeneration and tumor therapy for osteosarcoma treatment, a multifunctional calcium phosphate composite enabled by incorporation of bioactive FePSe3 -nanosheets within the cryogenic-3D-printed α-tricalcium phosphate scaffold (TCP-FePSe3 ) is explored. The TCP-FePSe3 scaffold exhibits remarkable tumor ablation ability due to the excellent NIR-II (1064 nm) photothermal property of FePSe3 -nanosheets. Moreover, the biodegradable TCP-FePSe3 scaffold can release selenium element to suppress tumor recurrence by activating of the caspase-dependent apoptosis pathway. In a subcutaneous tumor model, it is demonstrated that tumors can be efficiently eradicated via the combination treatment with local photothermal ablation and the antitumor effect of selenium element. Meanwhile, in a rat calvarial bone defect model, the superior angiogenesis and osteogenesis induced by TCP-FePSe3 scaffold have been observed in vivo. The TCP-FePSe3 scaffold possesses improved capability to promote the repair of bone defects via vascularized bone regeneration, which is induced by the bioactive ions of Fe, Ca, and P released during the biodegradation of the implanted scaffolds. The TCP-FePSe3 composite scaffolds fabricated by cryogenic-3D-printing illustrate a distinctive strategy to construct multifunctional platform for osteosarcoma treatment.

Antibiotic-associated vanishing bile duct syndrome: a real-world retrospective and pharmacovigilance database analysis.

PURPOSE: Vanishing bile duct syndrome (VBDS) is a rare, but potentially fatal adverse reaction triggered by certain medications. Few real-world studies have shown association between antibiotics and VBDS. We sought to quantify the risk and evaluate the clinical features of VBDS associated with antibiotics. METHODS: Data from 2004 to 2022 on VBDS events induced by antibiotics were retrieved from the FDA Adverse Event Reporting System (FAERS) database and disproportionality analyses were conducted. Furthermore, case reports from 2000 to 31 December 2022 on antibiotics-induced VBDS were retrieved for retrospective analysis. RESULTS: We collected 132 VBDS reports from the FAERS database. Fluoroquinolones had the greatest proportion and highest positive signal values of VBDS. The RORs (95% CIs) for antibiotics were fluoroquinolones 23.68 (18.12-30.95), macrolides 19.37 (13.58-27.62), carbapenems 17.39 (7.77-38.96), beta-lactam 13.28 (9.69-18.20), trimethoprim/sulfamethoxazole 9.05 (5.57-14.7), and tetracycline 4.02 (1.50-10.77). Twenty-three cases from 22 studies showed evidence of VBDS, beta-lactam (52.2%) was the most frequently reported agent. The median age was 45 years, the typical initial symptoms included rash (30.4%), fatigue/asthenia (26.1%), dark urine (21.7%) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) (21.7%). The median time to onset of VBDS was 2 weeks. All cases had abnormal liver function test, and the median level of total bilirubin was 23.6 mg/dl (range 3.2-80 mg/dl). Cessation of culprit drugs and treatment with ursodeoxycholic acid (83.3%) were not associated with improved outcomes (57.1%). CONCLUSION: This study identified thirteen antibacterial agents with significant reporting associations with VBDS. Fluoroquinolones may be a neglected agent of inducing VBDS.

Association of DNA methylation and transcriptome reveals epigenetic etiology of heart failure.

Epigenetic modifications viz. DNA methylation, histone modifications, and RNA-based alterations play a crucial role in the development of cardiovascular diseases. In this study, we investigated DNA methylation with an aim to reveal the epigenetic etiology of heart failure. Sprague-Dawley rats surviving myocardial infarction developed acute heart failure in 1 week. Genomic DNA methylation changes were profiled by bisulfite sequencing, and gene expression levels were analyzed by RNA-seq in failing and sham-operation hearts. A total of 3480 differentially methylated genes in the promoter regions including transcriptional start site and 1934 transcriptome-altered genes were identified in the defected hearts. Common differential genes were enriched by the gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and protein-protein interaction for HF phenotypes. Among these, Mettl11b, HDAC3, HDAC11, ubiquitination-related genes, and snoRNAs are new epigenetic classifiers that had not been reported yet, which may be important regulators in HF.

Spinophilin modulates pain through suppressing dendritic spine morphogenesis via negative control of Rac1-ERK signaling in rat spinal dorsal horn.

Both spinophilin (SPN, also known as neurabin 2) and Rac1 (a member of Rho GTPase family) are believed to play key roles in dendritic spine (DS) remodeling and spinal nociception. However, how SPN interacts with Rac1 in the above process is unknown. Here, we first demonstrated natural existence of SPN-protein phosphatase 1-Rac1 complex in the spinal dorsal horn (DH) neurons by both double immunofluorescent labeling and co-immunoprecipitation, then the effects of SPN over-expression and down-regulation on mechanical and thermal pain sensitivity, GTP-bound Rac1-ERK signaling activity, and spinal DS density were studied. Over-expression of SPN in spinal neurons by intra-DH pAAV-CMV-SPN-3FLAG could block both mechanical and thermal pain hypersensitivity induced by intraplantar bee venom injection, however it had no effect on the basal pain sensitivity. Over-expression of SPN also resulted in a significant decrease in GTP-Rac1-ERK activities, relative to naive and irrelevant control (pAAV-MCS). In sharp contrast, knockdown of SPN in spinal neurons by intra-DH pAAV-CAG-eGFP-U6-shRNA[SPN] produced both pain hypersensitivity and dramatic elevation of GTP-Rac1-ERK activities, relative to naive and irrelevant control (pAAV-shRNA [NC]). Moreover, knockdown of SPN resulted in increase in DS density while over-expression of it had no such effect. Collectively, SPN is likely to serve as a regulator of Rac1 signaling to suppress DS morphogenesis via negative control of GTP-bound Rac1-ERK activities at postsynaptic component in rat DH neurons wherein both mechanical and thermal pain sensitivity are controlled.

Validation of pre-operative risk scores of contrast-induced acute kidney injury in a Chinese cohort.

BACKGROUND: Pre-operative risk scores are more valuable than post-procedure risk scores because of lacking effective treatment for contrast-induced acute kidney injury (CI-AKI). A number of pre-operative risk scores have been developed, but due to lack of effective external validation, most of them are also difficult to apply accurately in clinical practice. It is necessary to review and validate the published pre-operative risk scores for CI-AKI. MATERIALS AND METHODS: We systematically searched PubMed and EMBASE databases for studies of CI-AKI pre-operative risk scores and assessed their calibration and discriminatory in a cohort of 2669 patients undergoing coronary angiography or percutaneous coronary intervention (PCI) from September 2007 to July 2017. The definitions of CI-AKI may affect the validation results, so three definition were included in this study, CI-AKI broad1 was defined as an increase in serum creatinine (Scr) of 44.2 µmol/L or 25%; CI-AKI broad2, an increase in Scr of 44.2 µmol/L or 50%; and CI-AKI-narrow, an increase in Scr of 44.2 µmol/L. The calibration of the model was assessed with the Hosmer-Lemeshow test and the discriminatory capacity was identified by C-statistic. RESULTS: Of the 8 pre-operative risk scores for CI-AKI identified, 7 were single-center study and only 1 was based on multi-center study. In addition, 7 of the scores were just validated internally and only Chen score was externally validated. In the validation cohort of 2669 patients, the incidence of CI-AKI ranged from 3.0%(Liu) to 16.4%(Chen) for these scores. Furthermore, the incidence of CI-AKI was 6.59% (178) for CI-AKI broad1, 1.44% (39) for CI-AKI broad2, and 0.67% (18) for CI-AKI-narrow. For CI-AKI broads, C-statistics varied from 0.44 to 0.57. For CI-AKI-narrow, the Maioli score had the best discrimination and calibration, what's more, the C-statistics of Maioli, Chen, Liu and Ghani was ≥0.7. CONCLUSION: Most pre-operative risk scores were established based on single-center studies and most of them lacked external validation. For CI-AKI broads, the prediction accuracy of all risk scores was low. The Maioli score had the best discrimination and calibration, when using the CI-AKI-narrow definition.

A Novel Laboratory-Based Model to Predict the Presence of Obstructive Coronary Artery Disease.

Commonly used tools to assess the probability of obstructive-coronary artery disease (CAD) were derived based on Caucasian cohorts, with their performance in China is still unknown. Furthermore, most were established based on non-laboratory variables, contributing to the limited predictive ability to some extent. Thus, we developed and internally validated a laboratory-based model with data from a Chinese cohort of 8963 inpatients, with suspected stable chest pain, referred to catheter-based coronary angiography (CAG) from September 2007 to April 2019, and then compared the present model's performance with the four most commonly used prediction tools, Coronary Artery Disease Consortium 1/2 Score (CAD1/2), Duke clinical score (DCS), and Diamond-Forrester score (DF). The final model was developed by random forest method, including 8 predictors derived from 70 variables. Five-fold cross-validation was performed to evaluate the model's prediction accuracy. In the external validation set, the present model showed a superior area under the receiver-operating curve (0.816), followed by DCS (0.66), CAD2 (0.61), CAD1 (0.59) and at last DF (0.58), respectively. Furthermore, the present model correctly classified 74.4% of obstructive-CAD patients as high-risk, and correctly classified more than one third of non-obstructive-CAD patients as low-risk. The present model's net reclassification improvement (NRI) showed a significant positive reclassification over CAD1 (NRI = 0.60, P < 0.001), DF (NRI = 0.59, P < 0.001), CAD2 (NRI = 0.57, P < 0.001), and DCS (NRI = 0.43, P < 0.001). Decision curve analysis demonstrated that the present model provided a larger net benefit compared with CAD1/2, DCS, and DF. In conclusion, the novel model, using 8 laboratory and non-laboratory variables, performed well in risk stratifying patients with suspected chest pain regarding the presence of obstructive-CAD in the present Chinese cohort.

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OBJECTIVES: Contrast-induced acute kidney injury (CI-AKI) is the third cause of hospital-acquired AKI, and existing clinical prevention and treatment measures such as hydration therapy and/or administration of antioxidants N-acetylcysteine treatment and other treatments still show little effect on the prevention and treatment of CI-AKI. This study aims to explore the effect of Danhong injection on prevention of CI-AKI. METHODS: A total of 12 867 patients, who received coronary angiography, percutaneous coronary intervention, enhanced CT or vascular intervention in a tertiary hospital, were enrolled for this study. Among them, 423 in the treatment group received intravenous drip of Danhong injection, and 12 444 in the control group received routine medicine. Propensity score matching was conducted to balance confounding factors between the 2 groups and then the prevention effect of Danhong injection on CI-AKI was compared between them. RESULTS: A total of 423 pairs of patients were matched successfully. The incidence of CI-AKI in the non-Danhong control group was higher than that in the Danhong treatment group (5.7% vs 2.4%). The difference between the 2 groups was statistically significant (P<0.05). CI-AKI occurred maily in the Stage 1 in both the non-Danhong control group and the Danhong treatment group. The number of patients with Stage 1 of AKI in the control group was more than that in the treatment group, and the difference was statistically significant (P<0.05). The incidence of AKI in Stage 2 and Stage 3 was less in both groups, and the difference was not statistically significant (P>0.05). CONCLUSIONS: The results of this study support the use of Danhong injection in the prevention of the Stage 1 of CI-AKI.

Development and validation of a more accurate estimating equation for glomerular filtration rate in a Chinese population.

Previously published equations to estimate glomerular filtration rate (GFR) have limited accuracy in Asian populations. We aimed to develop and validate a more accurate equation for estimated GFR (eGFR) in the Chinese population, using data from 8571 adults who were referred for direct measurement of GFR by renal dynamic imaging (mGFR) at 3 representative hospitals in China. Patients from the Third Xiangya Hospital were included in our development (n=1730) and internal validation sets (n=1042) and patients from the other hospitals comprised the external validation set (n=5799). We excluded patients who were prescribed medications known to influence the tubular secretion of creatinine, patients on dialysis, kidney transplant recipients, and patients with missing creatinine values or with creatinine >700 µmol/l. We derived a novel eGFR equation by linear regression analysis and compared the performance to 12 creatinine-based eGFR equations, including previously published equations for use in Chinese or Asian populations. In the development and internal validation sets, the novel Xiangya equation had high accuracy (accuracy within 30% [P30], 79.21% and 84.33%, respectively), low bias (mean difference between mGFR and eGFR, -1.97 and -1.85 ml/min per 1.73 m2, respectively), and high precision (interquartile range of the differences, 21.13 and 18.88 ml/min per 1.73 m2, respectively). In external validation, the Xiangya equation had the highest P30 among all eGFR equations, with P30 ≤ 75% for the other 12 equations. This novel equation provides more accurate GFR estimates in Chinese adults and could replace existing eGFR equations for use in the Chinese population.

A novel rat model of contrast-induced nephropathy based on dehydration.

BACKGROUND: Contrast-induced nephropathy (CIN) is a frequent cause of hospital-acquired acute kidney injury. Previous animal models developed to explore the pathogenesis of CIN were based primarily on surgery or indomethacin treatment. Thus, we sought to explore a novel CIN rat model comparable to the human CIN. METHODS AND RESULTS: Both serum creatinine and tubular injury score were used to assess the successful establishment of the present model. In our study, dehydration duration and the iohexol dosage were found to be the two most important factors to develop a rat CIN model. And, dehydration for 3 days plus furosemide (10 mL/kg) injection before iohexol (15 mL/kg) administration was demonstrated the optimal strategy. Renal injury induced by 15 mL/kg iohexol was almost twice more severe than 10 mL/kg. Moreover, significant renal function decrease, morphological damage and mitochondrial dysfunction occurred as early as 6 h after iohexol injection, not 24 h as previous studies reported. Unexpectedly, we firstly discovered that dehydration after iohexol administration did not increase the extent of renal damage, indicating that hydration after contrast media exposure may be ineffective. CONCLUSIONS: A novel CIN rat model based on dehydration and iohexol exposure was established and validated to assist in understanding and preventing CIN.

Evaluating tacrolimus pharmacokinetic models in adult renal transplant recipients with different CYP3A5 genotypes.

PURPOSE: Numerous studies have been conducted on the population pharmacokinetics of tacrolimus in adult renal transplant recipients. It has been reported that the cytochrome P450 (CYP) 3A5 genotype is an important cause of variability in tacrolimus pharmacokinetics. However, the predictive performance of population pharmacokinetic (PK) models of tacrolimus should be evaluated prior to their implementation in clinical practice. The aim of the study reported here was to test the predictive performance of these published PK models of tacrolimus. METHODS: A literature search of the PubMed and Web of Science databases ultimately led to the inclusion of eight one-compartment models in our analysis. We collected a total of 1715 trough concentrations from 174 patients. Predictive performance was assessed based on visual and numerical comparison bias and imprecision and by the use of simulation-based diagnostics and Bayesian forecasting. RESULTS: Of the eight one-compartment models assessed, seven showed better predictive performance in CYP3A5 extensive metabolizers in terms of bias and imprecision. Results of the simulation-based diagnostics also supported the findings. The model based on a Chinese population in 2013 (model 3) showed the best and most stable predictive performance in all the tests and was more informative in CYP3A5 extensive metabolizers. As expected, Bayesian forecasting improved model predictability. Diversity among models and between different CYP3A5 genotypes of the same model was also narrowed by Bayesian forecasting. CONCLUSIONS: Based on our results, we recommend using model 3 in CYP3A5 extensive metabolizers in clinical practice. All models had a poor predictive performance in CYP3A5 poor metabolizers, and they should be used with caution in this patient population. However, Bayesian forecasting improved the predictability and reduced differences, and thus the models could be applied in this latter patient population for the design of maintenance dose.

A 3,500-year tree-ring record of annual precipitation on the northeastern Tibetan Plateau.

An annually resolved and absolutely dated ring-width chronology spanning 4,500 y has been constructed using subfossil, archaeological, and living-tree juniper samples from the northeastern Tibetan Plateau. The chronology represents changing mean annual precipitation and is most reliable after 1500 B.C. Reconstructed precipitation for this period displays a trend toward more moist conditions: the last 10-, 25-, and 50-y periods all appear to be the wettest in at least three and a half millennia. Notable historical dry periods occurred in the 4th century BCE and in the second half of the 15th century CE. The driest individual year reconstructed (since 1500 B.C.) is 1048 B.C., whereas the wettest is 2010. Precipitation variability in this region appears not to be associated with inferred changes in Asian monsoon intensity during recent millennia. The chronology displays a statistical association with the multidecadal and longer-term variability of reconstructed mean Northern Hemisphere temperatures over the last two millennia. This suggests that any further large-scale warming might be associated with even greater moisture supply in this region.

Adsorption of methyl orange from aqueous solution using chitosan/diatomite composite.

A novel chitosan/diatomite composite was prepared by a simple mixture in the mass ratio to remove methyl orange (MO) from aqueous media in this study. The composite adsorbent was characterized by Fourier transform infrared spectroscopy and scanning electron microscopy analysis. The parameters to influence the adsorption of MO were studied under such conditions as kinetics, adsorption isotherm, pH effect, and thermodynamics. The results revealed that adsorption of MO was initially rapid and the equilibrium time was reached after 40 min. The optimal value of the pH was 5.0 for better adsorption. The equilibrium data were well fitted to the Langmuir isotherm compared to the Freundlich isotherm, and exhibited the highest capacity and a removal rate of 88.37% under an initial dye concentration of 50 mg/L. The kinetic data were well described by the pseudo-second order model. The thermodynamic calculations revealed that the sorption was viable, spontaneous, and exothermic under the conditions studied. In addition, the chitosan/diatomite composite had good adsorption and desorption performance with respect to reusability after six cycles. These results showed that the chitosan/diatomite could be considered as a potential adsorbent for the removal of MO in aqueous solution.

Chimeric Protein Template-Induced Shape Control of Bone Mineral Nanoparticles and Its Impact on Mesenchymal Stem Cell Fate.

Protein-mediated molecular self-assembly has become a powerful strategy to fabricate biomimetic biomaterials with controlled shapes. Here we designed a novel chimeric molecular template made of two proteins, silk fibroin (SF) and albumin (ALB), which serve as a promoter and an inhibitor for hydroxyapatite (HA) formation, respectively, to synthesize HA nanoparticles with controlled shapes. HA nanospheres were produced by the chimeric ALB-SF template, whereas HA nanorods were generated by the SF template alone. The success in controlling the shape of HA nanoparticles allowed us to further study the effect of the shape of HA nanoparticles on the fate of rat mesenchymal stem cells (MSCs). We found that the nanoparticle shape had a crucial impact on the cellular uptake and HA nanospheres were internalized in MSCs at a faster rate. Both HA nanospheres and nanorods showed no significant influence on cell proliferation and migration. However, HA nanospheres significantly promoted the osteoblastic differentiation of MSCs in comparison to HA nanorods. Our work suggests that a chimeric combination of promoter and inhibitor proteins is a promising approach to tuning the shape of nanoparticles. It also sheds new light into the role of the shape of the HA nanoparticles in directing stem cell fate.