Serum procalcitonin as a marker of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD).

BACKGROUND: Neonatal Intrahepatic Cholestasis (NICCD), as the early-age stage of Citrin deficiency involving liver dysfunction, lacks efficient diagnostic markers. Procalcitonin (PCT) has been identified as a biomarker for infection as well as various organ damage. This study aimed to explore the potential of PCT as a biomarker for NICCD. METHODS: In a single-center retrospective case-control study. Serum PCT concentrations before and after treatment of 120 NICCD patients, as the study group, were compared to the same number of cholestatic hepatitis patients, as the control group. The potential value of PCT to discriminate NICCD from control disease was further explored using Receiver Operating Characteristic (ROC) curve analysis and compared to those of other inflammatory markers. RESULTS: There was a significantly higher level of PCT in NICCD patients than in the control group. PCT concentrations were only weakly correlated with neutrophil counts and CRP levels (p ˂ 0.05). At a cut-off value of 0.495 ng/mL, PCT exhibited a significantly higher diagnostic value compared to other inflammatory markers for discriminating NICCD from the control, with a sensitivity of 90.8 % and specificity of 98.3 %. CONCLUSION: PCT might be used as an initial biomarker to discriminate children with NICCD from another hepatitis disease.

Application of Recombinant Human Superoxide Dismutase in Radical Concurrent Chemoradiotherapy for Cervical Cancer to Prevent and Treat Radiation-induced Acute Rectal Injury: A Multicenter, Randomized, Open-label, Prospective Trial.

PURPOSE: The purpose of this study was to evaluate the efficacy of recombinant human superoxide dismutase (rhSOD) enemas in radiation-induced acute rectal injury (RARI) in patients with locally advanced cervical cancer. METHODS AND MATERIALS: In this phase 3, randomized, open-label trial (NCT04819685) conducted across 14 medical centers in China from June 2021 to August 2023, all patients received concurrent chemoradiation therapy (CCRT). The experimental group was treated with a rhSOD enema during chemoradiation therapy, and the control group had no enema. The Common Terminology Criteria for Adverse Events (version 5.0) was used to evaluate radiation therapy-induced side effects. Endoscopic appearance was assessed using the Vienna Rectoscopy Score. The primary endpoint in the acute phase was the occurrence rate and duration of grade ≥1 (≥G1) diarrhea during CCRT. Secondary endpoints included the occurrence rate and duration of ≥G2 and ≥G3 diarrhea, ≥G1 and ≥G2 diarrhea lasting at least 3 days, and damage to the rectal mucosa due to radiation therapy measured by endoscopy. RESULTS: Two hundred and eighty-three patients were randomly divided into the experimental (n = 141) or control group (n = 142). The mean number of ≥G1 and ≥G2 diarrhea days were significantly lower in the experimental group than in the control group (3.5 and 0.8 days vs 14.8 and 4.5 days, respectively; P < .001). The incidence of ≥G2 diarrhea decreased from 53.6% to 24.1% when rhSOD enemas were used. Use of antidiarrheals was lower in the experimental group (36.2% vs 55.7%, P < .001). Three patients felt intolerable or abdominal pain after rhSOD enema. RARI grades in the experimental group tended to be lower than those in the control group (P = .061). Logistic regression analysis revealed that rhSOD enema was associated with a lower occurrence rate of ≥G1/2 diarrhea for at least 3 days (P < .001). CONCLUSIONS: The results of this study suggest that rhSOD enema is safe and significantly reduces the incidence, severity, and duration of RARI, protecting the rectal mucosa.

A review on sustainable management of biomass: physicochemical modification and its application for the removal of recalcitrant pollutants-challenges, opportunities, and future directions.

Adsorption is one of the most efficient methods for remediating industrial recalcitrant wastewater due to its simple design and low investment cost. However, the conventional adsorbents used in adsorption have several limitations, including high cost, low removal rates, secondary waste generation, and low regeneration ability. Hence, the focus of the research has shifted to developing alternative low-cost green adsorbents from renewable resources such as biomass. In this regard, the recent progress in the modification of biomass-derived adsorbents, which are rich in cellulosic content, through a variety of techniques, including chemical, physical, and thermal processes, has been critically reviewed in this paper. In addition, the practical applications of raw and modified biomass-based adsorbents for the treatment of industrial wastewater are discussed extensively. In a nutshell, the adsorption mechanism, particularly for real wastewater, and the effects of various modifications on biomass-based adsorbents have yet to be thoroughly studied, despite the extensive research efforts devoted to their innovation. Therefore, this review provides insight into future research needed in wastewater treatment utilizing biomass-based adsorbents, as well as the possibility of commercializing biomass-based adsorbents into viable products.

Contrast-enhanced ultrasound for differentiating benign from malignant focal solid renal lesions in pediatric patients.

The contrast-enhanced ultrasound (CEUS) has been mainly applied to adults to differentiate benign and malignant renal lesions, however, the characteristics of CEUS in pediatric has not been as well studied as in adults. In the present work, the eligible pediatric patients who underwent renal CEUS between March 2016 and February 2023 were retrospectively analyzed. It included 20 lesions (median diameter, 8.4 cm; range, 1.8-18.0 cm) from 20 patients (median age, 28.0 months; range, 3.0-212.0 months; 9 boys) in malignant group and 5 lesions (median diameter, 3.8 cm; range, 1.3-7.5 cm) from 5 patients (median age, 25.0 months; range, 0.7-216.0 months; 2 boys) in benign group. The diagnostic performance was assessed. Nonparametric and Chi-square tests were performed. With hyperenhancement plus wash-out, CEUS showed a sensitivity of 95.0% [95% confidence interval (CI): 75.1%, 99.9%], a specificity of 80.0% (CI: 28.4%, 99.5%), a positive predictive value of 95.0% (CI: 75.1%, 99.9%) and a negative predictive value of 80.0% (CI: 28.4%, 99.5%). It suggested that CEUS is a valuable technique for identifying between malignant and benign renal lesions in children.

Associations of BRAFV600E mutation with the American College of Radiology Thyroid Imaging Reporting and Data System and clinicopathological characteristics in pediatric patients with papillary thyroid carcinoma.

BACKGROUND: Identifying the associations between BRAFV600E mutation, the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) and clinicopathological characteristics could assist in making appropriate treatment strategies for pediatric patients with papillary thyroid carcinoma. OBJECTIVE: To retrospectively assess the associations between BRAFV600E mutation, TI-RADS, and clinicopathological characteristics in pediatric patients with papillary thyroid carcinoma. MATERIALS AND METHODS: Between May 2013 and May 2023, pediatric patients with papillary thyroid carcinoma who underwent thyroidectomy were retrospectively evaluated. Univariate and multivariate logistic regression analyses were performed to determine the associations between BRAFV600E mutation, TI-RADS, and clinicopathological characteristics. The diagnostic performance of TI-RADS to predict BRAFV600E mutation was assessed. RESULTS: The BRAFV600E mutation was found in 59.1% (39/66) of pediatric patients with papillary thyroid carcinoma. Multivariate analyses showed that hypoechoic/very hypoechoic [odds ratio (OR) = 8.48; 95% confidence interval (CI) = 1.48-48.74); P-value = 0.02] and punctate echogenic foci (OR = 24.3; 95% CI = 3.80-155.84; P-value = 0.001) were independent factors associated with BRAFV600E mutation. In addition, BRAFV600E mutation was significantly associated with TI-RADS 5 (OR = 12.61; 95% CI = 1.28-124.49; P-value = 0.03). There were no associations between BRAFV600E mutation and nodule size, composition, shape, margin, cervical lymph node metastasis, or Hashimoto's thyroiditis (P-value > 0.05). Combined with hypoechoic/very hypoechoic and punctate echogenic foci, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 89.7%, 85.2%, 89.7%, 85.2%, and 87.9%, respectively. CONCLUSIONS: Hypoechoic/very hypoechoic, punctate echogenic foci, and TI-RADS 5 are independently associated with BRAFV600E mutation in pediatric patients with papillary thyroid carcinoma.

Microwave synthesized novel biomass carbon dots applied in the fluorescent detection of crystal violet.

To establish a new method for detecting crystal violet (CV), a harmful dye, herein, a genre of novel biomass carbon dots (CDs) was synthesized via a microwave method and employed as a fluorescent probe, in which water spinach and polyethylene glycol (PEG) performed as raw materials. Based on the inner filter effect (IFE) between the luminescent CDs and CV, the blue emission of this probe at 430 nm could be quenched by CV. Hence, a new strategy was proposed to selectively determine CV in aquaculture ambient. Moreover, under the optimal experiment conditions, this method showed a good linearity between the concentration of CV (c) and fluorescence quenching rate (ΔF/F0) in the concentration range of 4-200 µmol/L with the corresponding correlation coefficient (r) and the detection limit of 0.997 and 710 nmol/L, respectively. With advantages of environmental protectivity, sensitivity, affordability, and user-friendliness, the facilely fabricated CDs could be successfully applied in detecting CV in aquaculture samples, providing a technical foundation for monitoring the pollution of CV and ensuring the quality and safety of aquatic products.

Human-derived fecal microbiota transplantation alleviates social deficits of the BTBR mouse model of autism through a potential mechanism involving vitamin B6 metabolism.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by social communication deficiencies and stereotypic behaviors influenced by hereditary and/or environmental risk factors. There are currently no approved medications for treating the core symptoms of ASD. Human fecal microbiota transplantation (FMT) has emerged as a potential intervention to improve autistic symptoms, but the underlying mechanisms are not fully understood. In this study, we evaluated the effects of human-derived FMT on behavioral and multi-omics profiles of the BTBR mice, an established model for ASD. FMT effectively alleviated the social deficits in the BTBR mice and normalized their distinct plasma metabolic profile, notably reducing the elevated long-chain acylcarnitines. Integrative analysis linked these phenotypic changes to specific Bacteroides species and vitamin B6 metabolism. Indeed, vitamin B6 supplementation improved the social behaviors in BTBR mice. Collectively, these findings shed new light on the interplay between FMT and vitamin B6 metabolism and revealed a potential mechanism underlying the therapeutic role of FMT in ASD.IMPORTANCEAccumulating evidence supports the beneficial effects of human fecal microbiota transplantation (FMT) on symptoms associated with autism spectrum disorder (ASD). However, the precise mechanism by which FMT induces a shift in the microbiota and leads to symptom improvement remains incompletely understood. This study integrated data from colon-content metagenomics, colon-content metabolomics, and plasma metabolomics to investigate the effects of FMT treatment on the BTBR mouse model for ASD. The analysis linked the amelioration of social deficits following FMT treatment to the restoration of mitochondrial function and the modulation of vitamin B6 metabolism. Bacterial species and compounds with beneficial roles in vitamin B6 metabolism and mitochondrial function may further contribute to improving FMT products and designing novel therapies for ASD treatment.

A Rare Case of Atypical Hemolytic Uremic Syndrome (aHUS) Precipitated by Dengue and the Treatment Landscape in Singapore.

Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by uncontrolled complement activation due to complement dysregulation. It is often triggered by precipitating events such as infections, inflammation, pregnancy, or medications. Dengue, an endemic viral infection in Southeast Asia, can activate the complement pathway, thereby triggering aHUS in genetically susceptible individuals. Here, we present the case of a 33-year-old male who presented with Dengue fever and subsequently developed aHUS. Plasma exchange (PLEX) successfully normalized his neurological status and hematological parameters. Although his renal function improved, it failed to normalize. Eculizumab, a monoclonal antibody that inhibits C5, was administered for a total of six months. The treatment was successfully discontinued without evidence of relapse after six months of follow-up. This case report demonstrates the safety of discontinuing eculizumab in patients who do not possess pathogenic mutations or variants in complement factors.

Hybrid machine learning model based predictions for properties of poly(2-hydroxyethyl methacrylate)-poly(vinyl alcohol) composite cryogels embedded with bacterial cellulose.

Supermacroporous composite cryogels with enhanced adjustable functionality have received extensive interest in bioseparation, tissue engineering, and drug delivery. However, the variations in their components significantly impactfinal properties. This study presents a two-step hybrid machine learning approach for predicting the properties of innovative poly(2-hydroxyethyl methacrylate)-poly(vinyl alcohol) composite cryogels embedded with bacterial cellulose (pHEMA-PVA-BC) based on their compositions. By considering the ratios of HEMA (1.0-22.0 wt%), PVA (0.2-4.0 wt%), poly(ethylene glycol) diacrylate (1.0-4.5 wt%), BC (0.1-1.5 wt%), and water (68.0-96.0 wt%) as investigational variables, overlay sampling uniform design (OSUD) was employed to construct a high-quality dataset for model development. The random forest (RF) model was used to classify the preparation conditions. Then four models of artificial neural network, RF, gradient boosted regression trees (GBRT), and XGBoost were developed to predict the basic properties of the composite cryogels. The results showed that the RF model achieved an accurate three-class classification of preparation conditions. Among the four models, the GBRT model exhibited the best predictive performance of the basic properties, with the mean absolute percentage error of 16.04 %, 0.85 %, and 2.44 % for permeability, effective porosity, and height of theoretical plate (1.0 cm/min), respectively. Characterization results of the representative pHEMA-PVA-BC composite cryogel showed an effective porosity of 81.01 %, a permeability of 1.20 × 10-12 m2, and a range of height of theoretical plate between 0.40-0.49 cm at flow velocities of 0.5-3.0 cm/min. These indicate that the pHEMA-PVA-BC cryogel was an excellent material with supermacropores, low flow resistance and high mass transfer efficiency. Furthermore, the model output demonstrates that the alteration of the proportions of PVA (0.2-3.5 wt%) and BC (0.1-1.5 wt%) components in composite cryogels resulted in significant changes in the material basic properties. This work represents an attempt to efficiently design and prepare target composite cryogels using machine learning and providing valuable insights for the efficient development of polymers.

Active metabolomics identify potential functional metabolites for preeclampsia prevention.

BACKGROUND: Preeclampsia (PE) is a leading cause of maternal and fetal morbidity and mortality, with limited effective clinical treatment options. Active metabolomics offers a promising approach to uncover metabolic changes in PE and identify potential biomarkers or therapeutic targets. This study performed untargeted metabolomics using LC-MS to compare serum samples from preeclampsia and normal pregnancies. METHODS: We performed untargeted metabolomics using liquid chromatography-mass spectrometry (LC-MS) to compare serum samples from PE patients and normal pregnancies. We analyzed the alterations in metabolites and conducted functional experiments to assess the effects of LysoPE(16:0) on trophoblast cell invasion and migration. Mechanistic studies were performed to explore the potential targeting of GSK-3ß by LysoPE(16:0). RESULTS: Our metabolomics analysis revealed significant alterations in several metabolites, including lysophosphatidylcholines and organic acids. Notably, LysoPE(16:0) was found to be downregulated in the serum of PE patients. Functional experiments demonstrated that LysoPE(16:0) could promote trophoblast cell invasion and migration. Mechanistic studies suggest that the protective effect of LysoPE(16:0) against PE might be mediated through the modulation of the GSK-3ß/ß-Catenin pathway, with LysoPE(16:0) potentially targeting the GSK-3ß protein. CONCLUSIONS: Our findings highlight the potential role of LysoPE(16:0) in the pathophysiology of PE and its ability to modulate the GSK-3ß/ß-Catenin pathway. These results provide new insights into the metabolic changes associated with PE and suggest that LysoPE(16:0) could serve as a promising biomarker or therapeutic target for the prevention and treatment of PE.

Decoupling of gray and white matter functional networks in cognitive impairment induced by occupational aluminum exposure.

Aluminum (Al) is a low-toxic, accumulative substance with neurotoxicity properties that adversely affect human cognitive function. This study aimed to investigate the neurobiological mechanisms underlying cognitive impairment resulting from occupational Al exposure. Resting-state functional magnetic resonance imaging was conducted on 54 individuals with over 10 years of Al exposure. Al levels were measured, and cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Subsequently, the K-means clustering algorithm was employed to identify functional gray matter (GM) and white matter (WM) networks. Two-sample t-tests were conducted between the cognition impairment group and the control group. Al exhibited a negative correlation with MoCA scores. Participants with cognitive impairment demonstrated reduced functional connectivity (FC) between the middle cingulum network (WM1) and anterior cingulum network (WM2), as well as between the executive control network (WM6) and limbic network (WM10). Notably, decreased FCs were observed between the executive control network (GM5) and WM1, WM4, WM6, and WM10. Additionally, the FC of GM5-GM4 and WM1-WM2 negatively correlated with Trail Making Test Part A (TMT-A) scores. Prolonged Al accumulation detrimentally affects cognition, primarily attributable to executive control and limbic network disruptions.

Food essentialism: Implications for expectations and perceptions of the properties of processed foods.

Despite the impact of processed foods on health, sustainability, and food security, consumers vary greatly in expectations about and preferences for processed foods. Essentialism is the lay belief that items in a category share a fundamental and immutable essence that generates the category's defining characteristics. Although essentialism may be an important determinant of consumers' cognitions about processed foods, there has been limited investigation of essentialism's role in food-related perceptions. Across two studies (n=598 total), we used a novel measure of food essentialism to examine whether individual differences in beliefs about foods as having essences (food essentialism) are related to perceptions of foods retaining more of their natural characteristics (sensory and nutritive properties) despite their level of processing. Across diverse food categories (meats, vegetables, fruits, legumes, dairy), higher levels of perceived food processing were associated with lower perceived retention of naturalness, nutritiousness, natural taste, functional post-ingestive benefits, and acceptability (liking). However, participants endorsing greater (vs. lower) food essentialism beliefs exhibited weaker relationships between perceived processing and these characteristics. We also observed variations across food categories in relationships between perceived level of processing and food properties, suggesting that some foods (i.e., milk-based products) are perceived to possess essences that are more robust despite undergoing higher levels of processing. These findings demonstrate that food-specific essentialism beliefs may be a fundamental determinant of consumers' expectations of how human intervention, such as processing, affects natural properties of foods. These beliefs may be a promising target for future research to shift consumer acceptance of processed foods.

Combined intravenous and intra-arterial thrombolysis in hyperacute cerebral ischemia without significant corresponding vascular occlusion/stenosis: A Preliminary investigation.

Objective: In this study, we assessed the efficacy and safety of various thrombolytic treatment protocols in patients with hyperacute cerebral infarction. Methods: Patients diagnosed with acute ischemic stroke within 6 h of symptom onset and with brain computer tomography angiography confirming the absence of major vessel stenosis or occlusion were eligible for this study. The enrolled patients were subsequently randomized into two groups: all the groups received the standard intravenous thrombolysis treatment with rt-PA (0.9 mg/kg), and the experimental group underwent sequential intra-arterial thrombolysis treatment with alteplase (0.3 mg/kg, with a maximum dose of 22 mg), administered directly into the target vessel via a microcatheter. Both groups were closely monitored for changes in their National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin scale score, hemorrhage rate, all-cause mortality rate, and the rate of favorable outcomes at 90 ± 7 days. Results: Ninety-four participants were enrolled in this study, with both the control and experimental groups initiating intravenous injection of rt-PA at a median time of 29 min. For the experimental group, the median time for arterial puncture was 123 min. Baseline data for both groups were similar (P > 0.05). Hemorrhagic transformation occurred in 24.47 % (23 patients), with a lower intracranial hemorrhage rate observed in the experimental group compared to the control group (15.2 % vs 33.3 %, P < 0.05). Asymptomatic hemorrhage rates were 8.7 % for the experimental group and 12.5 % for the control group, with no hemorrhage detected in other locations. Post-treatment median NIHSS scores were lower in the experimental group than in the control group (7 vs 9, P < 0.05), but short-term NIHSS scores were similar (P > 0.05). A higher proportion of patients in the experimental group achieved favorable outcomes compared to the control group (87.0 % vs 43.8 %, P < 0.05). Conclusion: In patients with acute ischemic stroke with an onset time of ≤6 h and no major intracranial vessel occlusion, combining rt-PA intravenous thrombolysis with intra-arterial thrombolysis via a microcatheter might yield superior functional outcomes.

The NeuroProtect Formula: A Preventive Approach to AD Targeting the HIF-1/PI3K-AKT Signaling Pathway Evaluated through In Vivo, In Vitro, and Network Pharmacology Approaches.

OBJECTIVE: Alzheimer's Disease (AD) is a progressive neurodegenerative disorder with limited options for reversing its middle-to-late stages. Early intervention is crucial to slow down disease progression. This study aimed to investigate the potential of the NeuroProtect (NP) formula, a combination of geniposide and Panax notoginseng saponins, in preventing AD. We evaluated the effects of the NP formula on amyloid plaque accumulation, neuronal degeneration, and molecular signaling pathways using in vivo and in vitro models. METHODS: To predict functional pathways and potential downstream targets of NP intervention, we employed network pharmacology. The preventative impact of the NP formula was assessed using APP/PS1 mice. We conducted HE staining, ELISA assay, Golgi staining, and immunohistochemistry to detect the protective effect of NP. Additionally, cell experiments were performed to assess cell activity and target protein expression. RESULTS: Network pharmacology analysis revealed 145 drug-disease interactions and identified 5 core active targets associated with AD. Molecular docking results demonstrated strong binding affinity between the components of the NP formula (GP, GN-Rb1, GN-Rg1, NS-R1) and target proteins (STAT3, HIF1A, TLR4, mTOR, VEGFA). Notably, the binding energy between NS-R1 and mTOR was -11.4kcal/mol. Among the top 10 enriched KEGG pathways, the HIF-1 and PI3K-AKT signaling pathways were highlighted. In vivo experiments demonstrated that the NP formula significantly ameliorated pathological changes, decreased the Aß42/Aß40 ratio in the hippocampus and cortex, and increased dendritic spine density in the CA1 region during the early stage of AD. In vitro experiments further illustrated the NP formula's ability to reverse the inhibitory effects of Aß25-35 on cell viability and regulate the expression of Tlr4, Mtor, Hif1a, Stat3, and Vegfa. CONCLUSION: Our findings suggest that NP exhibits neuroprotective effects during the early stages of AD, positioning it as a potential candidate for AD prevention. The NP formula may exert its preventive effects through the HIF-1/PI3K-AKT signaling pathway, with mTOR identified as a key target.

Ultrasound elastography predicts anticoagulation in lower extremity deep vein thrombosis.

OBJECTIVE: To investigate predictors of anticoagulation efficacy in deep venous thrombosis (DVT) by ultrasound elastography (UE). METHODS: The basic clinical, laboratory and ultrasound treatment data of fifty-eight patients with DVT were collected and analyzed. Then the results of ultrasound after 3-month anticoagulation treatment were compared among different groups. Multiple logistic regression analysis was used to identify independent risk factors that affected anticoagulation efficacy. The predictive efficacy of each independent risk factor was accessed by drawing operating characteristic (ROC) curves. RESULTS: According to the regression analysis, the elastic modulus (OR = 0.631, P = 0.001) and strain rate ratio (OR = 0.332, P = 0.006) were identified as independent risk factors for the effectiveness of anticoagulation therapy in patients with DVT. According to the ROC curves, elastic modulus and strain rate ratio could predict effective anticoagulation therapy for DVT, and the optimal threshold values were 22.10 kPa and 1.80 respectively. The corresponding AUC values were 0.879 and 0.854, with a sensitivity of 71.4% and 59.5%, a specificity of 93.7%, and a Youden index of 65.1% and 62.7%, respectively. CONCLUSIONS: The elastic modulus (≤22.10 kPa) or strain rate ratio (≤1.80) of the thrombus were independent predictors for the effectiveness of anticoagulation therapy.

6-O-angeloylplenolin inhibits osteoclastogenesis in vitro via suppressing c-Src/NF-κB/NFATc1 pathways and ameliorates bone resorption in collagen-induced arthritis mouse model.

One of the effective therapeutic strategies to treat rheumatoid arthritis (RA)-related bone resorption is to target excessive activation of osteoclasts. We discovered that 6-O-angeloylplenolin (6-OAP), a pseudoguaianolide from Euphorbia thymifolia Linn widely used for the treatment of RA in traditional Chinese medicine, could inhibit RANKL-induced osteoclastogenesis and bone resorption in both RAW264.7 cells and BMMs from 1 µM and protect a collagen-induced arthritis (CIA) mouse model from bone destruction in vivo. The severity of arthritis and bone erosion observed in paw joints and the femurs of the CIA model were attenuated by 6-OAP administered at both dosages (1 or 5 mg/kg, i.g.). BMD, Tb.N and BV/TV were also improved by 6-OAP treatment. Histological analysis and TRAP staining of femurs further confirmed the protective effects of 6-OAP on bone erosion, which is mainly due to reduced osteoclasts. Molecular docking indicated that c-Src might be a target of 6-OAP and phosphorylation of c-Src was suppressed by 6-OAP treatment. CETSA and SPR assay further confirmed the potential interaction between 6-OAP and c-Src. Three signaling molecules downstream of c-Src that are vital to the differentiation and function of osteoclasts, NF-κB, c-Fos and NFATc1, were also suppressed by 6-OAP in vitro. In summary, the results demonstrated that the function of c-Src was disrupted by 6-OAP, which led to the suppression of downstream signaling vital to osteoclast differentiation and function. In conclusion, 6-OAP has the potential to be further developed for the treatment of RA-related bone erosion.

Dual-signal detection of tannic acid in red wines based on the peroxidase activity of carbon dots.

Herein, a novel type of phosphorus and iron-doped carbon dot (P,Fe-CD) with outstanding peroxidase activity and excellent fluorescence performance was hydrothermally synthesized to colorimetrically and fluorimetrically detect tannic acid (TA). In the presence of 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2, the P,Fe-CDs could oxidize colorless TMB to a blue oxidation product (oxTMB) resulting in an increased value of absorbance. Simultaneously, the fluorescence intensity of P,Fe-CDs at 430 nm could be quenched owing to the fluorescence resonance energy transfer (FRET) between P,Fe-CDs and the generated oxTMB. Meanwhile, after adding the TA to the system containing TMB, H2O2 and P,Fe-CDs, the value of absorbance could be decreased and the fluorescence could be recovered because of the reduction reaction between TA and oxTMB. Therefore, fluorescence intensity and value of absorbance could be applied to quantitatively detect TA with good linearities between the concentration of TA and the fluorescence intensity/value of absorbance (0.997 and 0.997 for the colorimetric signal and fluorimetric one, respectively) and low limits of detection (0.093 µmol L-1 and 0.053 µmol L-1 for the colorimetry and the fluorimetry, respectively), which was successfully applied to the detection of TA in red wines. Moreover, we applied a smartphone-assisted method to the point-of-care detection of TA with accurate results, providing a new technique for TA detection and food quality monitoring.

Rovibrational Energies of 13C16O2 Determined with Kilohertz Accuracy.

Accurate spectroscopic data of carbon dioxide are widely used in many important applications, such as carbon monitoring missions. Here, we present comb-locked cavity ring-down saturation spectroscopy of the second most abundant isotopologue of CO2, 13C16O2. We determined the positions of 88 lines in three vibrational bands in the 1.6 µm region, 30011e/30012e/30013e-00001e, with an accuracy of a few kHz. Based on the analysis of combination differences, we obtained for the first time the ground-state rotational energies with kHz accuracy. We also provide a set of hybrid line positions for 150 13C16O2 transitions. The rotational energies (J < 50) in the 30013e vibrational state can be fitted by a set of rotational and centrifugal constants with deviations within a few kHz, indicating that the 30013e state is free of perturbations. These precise isotopic line positions will be utilized to improve the Hamiltonian model and quantitative remote sensing of carbon dioxide. Moreover, they will help to track changes in the carbon source and sink through isotopic analysis.

Self-assembly of an amino acid derivative as an anode interface layer for advanced alkaline Al-air batteries.

Alkaline Al-air batteries (AABs) are gaining increasing attention for large-scale energy storage systems due to their attractive intrinsic safety and cost-effectiveness. Nonetheless, the future development of AABs is substantially hampered by water-induced self-corrosion processes on the Al anode. In this work, we introduce an amino acid derivative, namely Nα-Boc-N1-formyl-L-tryptophan (NBLT), into a 4 M NaOH electrolyte to construct a unique layer that can effectively regulate the surface microstructure of the Al anode. The findings of the experiments show that NBLT can be used as a reliable corrosion inhibitor. The effectiveness of such inhibitors increases with NBLT concentration, reaching a maximum of 73.9% at 1.5 mM. In comparison to the pristine condition, there is a significant increase in anode utilization from 31.8% to 82.9%, capacity density from 947.9 to 2469.1 mA h g-1, and energy density from 1261.6 to 3384.6 W h kg-1. Theoretical calculations indicate that the carboxyl moieties present in the NBLT molecule establish coordination bonds with the Al atoms, thereby exerting a dominant role in the formation of the self-assembled barrier. The present investigation paves an effective strategy to inhibit reactions between anodes and electrolytes for advanced AABs.

OPEN STOMATA 1 phosphorylates CYCLIC NUCLEOTIDE-GATED CHANNELs to trigger Ca2+ signaling for abscisic acid-induced stomatal closure in Arabidopsis.

Multiple cyclic nucleotide-gated channels (CNGCs) are abscisic acid (ABA)-activated Ca2+ channels in Arabidopsis (Arabidopsis thaliana) guard cells. In particular, CNGC5, CNGC6, CNGC9, and CNGC12 are essential for ABA-specific cytosolic Ca2+ signaling and stomatal movements. However, the mechanisms underlying ABA-mediated regulation of CNGCs and Ca2+ signaling are still unknown. In this study, we identified the Ca2+-independent protein kinase OPEN STOMATA 1 (OST1) as a CNGC activator in Arabidopsis. OST1-targeted phosphorylation sites were identified in CNGC5, CNGC6, CNGC9, and CNGC12. These CNGCs were strongly inhibited by Ser-to-Ala mutations and fully activated by Ser-to-Asp mutations at the OST1-targeted sites. The overexpression of individual inactive CNGCs (iCNGCs) under the UBIQUITIN10 promoter in wild-type Arabidopsis conferred a strong dominant-negative-like ABA-insensitive stomatal closure phenotype. In contrast, expressing active CNGCs (aCNGCs) under their respective native promoters in the cngc5-1 cngc6-2 cngc9-1 cngc12-1 quadruple mutant fully restored ABA-activated cytosolic Ca2+ oscillations and Ca2+ currents in guard cells, and rescued the ABA-insensitive stomatal movement mutant phenotypes. Thus, we uncovered that ABA elicits cytosolic Ca2+ signaling via an OST1-CNGC module, in which OST1 functions as a convergence point of the Ca2+-dependent and -independent pathways in Arabidopsis guard cells.