HOO• as the Chain Carrier for the Autocatalytic Photooxidation of Benzylic Alcohols.

The oxidation of benzylic alcohols is an important transformation in modern organic synthesis. A plethora of photoredox protocols have been developed to achieve the aerobic oxidation of alcohols into carbonyls. Recently, several groups described that ultraviolet (UV) or purple light can initiate the aerobic oxidation of benzylic alcohols in the absence of an external catalyst, and depicted different mechanisms involving the photoinduction of •O2- as a critical reactive oxygen species (ROS). However, based on comprehensive mechanistic investigations, including control experiments, radical quenching experiments, EPR studies, UV-vis spectroscopy, kinetics studies, and density functional theory calculations (DFT), we elucidate here that HOO•, which is released via the H2O2 elimination of α-hydroxyl peroxyl radicals [ArCR(OH)OO•], serves as the real chain carrier for the autocatalytic photooxidation of benzylic alcohols. The mechanistic ambiguities depicted in the precedent literature are clarified, in terms of the crucial ROS and its evolution, the rate-limiting step, and the primary radical cascade. This work highlights the necessity of stricter mechanistic analyses on UV-driven oxidative reactions that involve aldehydes' (or ketones) generation.

Enhancing zinc biofortification and mitigating cadmium toxicity in soil-earthworm-spinach systems using different zinc sources.

Cadmium (Cd) pollution poses significant threats to soil organisms and human health by contaminating the food chain. This study aimed to assess the impact of various concentrations (50, 250, and 500 mg·kg-1) of zinc oxide nanoparticles (ZnO NPs), bulk ZnO, and ZnSO4 on morphological changes and toxic effects of Cd in the presence of earthworms and spinach. The results showed that Zn application markedly improved spinach growth parameters (such as fresh weight, plant height, root length, and root-specific surface area) and root morphology while significantly reducing Cd concentration and Cd bioconcentration factors (BCF-Cd) in spinach and earthworms, with ZnO NPs exhibiting the most pronounced effects. Earthworm, spinach root, and shoot Cd concentration decreased by 82.3 %, 77.0 %, and 75.6 %, respectively, compared to CK. Sequential-step extraction (BCR) analysis revealed a shift in soil Cd from stable to available forms, consistent with the available Cd (DTPA-Cd) results. All Zn treatments significantly reduced Cd accumulation, alleviated Cd-induced stress, and promoted spinach growth, with ZnO NPs demonstrating the highest Cd reduction and Zn bioaugmentation efficiencies compared to bulk ZnO and ZnSO4 at equivalent concentrations. Therefore, ZnO NPs offer a safer and more effective option for agricultural production and soil heavy metal pollution management than other Zn fertilizers.

A Deep Learning Approach to Predict Recanalization First-Pass Effect following Mechanical Thrombectomy in Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Following endovascular thrombectomy in patients with large-vessel occlusion stroke, successful recanalization from 1 attempt, known as the first-pass effect, has correlated favorably with long-term outcomes. Pretreatment imaging may contain information that can be used to predict the first-pass effect. Recently, applications of machine learning models have shown promising results in predicting recanalization outcomes, albeit requiring manual segmentation. In this study, we sought to construct completely automated methods using deep learning to predict the first-pass effect from pretreatment CT and MR imaging. MATERIALS AND METHODS: Our models were developed and evaluated using a cohort of 326 patients who underwent endovascular thrombectomy at UCLA Ronald Reagan Medical Center from 2014 to 2021. We designed a hybrid transformer model with nonlocal and cross-attention modules to predict the first-pass effect on MR imaging and CT series. RESULTS: The proposed method achieved a mean 0.8506 (SD, 0.0712) for cross-validation receiver operating characteristic area under the curve (ROC-AUC) on MR imaging and 0.8719 (SD, 0.0831) for cross-validation ROC-AUC on CT. When evaluated on the prospective test sets, our proposed model achieved a mean ROC-AUC of 0.7967 (SD, 0.0335) with a mean sensitivity of 0.7286 (SD, 0.1849) and specificity of 0.8462 (SD, 0.1216) for MR imaging and a mean ROC-AUC of 0.8051 (SD, 0.0377) with a mean sensitivity of 0.8615 (SD, 0.1131) and specificity 0.7500 (SD, 0.1054) for CT, respectively, representing the first classification of the first-pass effect from MR imaging alone and the first automated first-pass effect classification method in CT. CONCLUSIONS: Results illustrate that both nonperfusion MR imaging and CT from admission contain signals that can predict a successful first-pass effect following endovascular thrombectomy using our deep learning methods without requiring time-intensive manual segmentation.

Glycine/alginate-based piezoelectric film consisting of a single, monolithic ß-glycine spherulite towards flexible and biodegradable force sensor.

Development of piezoelectric biomaterials with high piezoelectric performance, while possessing excellent flexibility, biocompatibility, and biodegradability still remains a great challenge. Herein, a flexible, biocompatible and biodegradable piezoelectric ß-glycine-alginate-glycerol (Gly-Alg-Glycerol) film with excellent in vitro and in vivo sensing performance was developed. Remarkably, a single, monolithic ß-glycine spherulite, instead of more commonly observed multiple spherulites, was formed in alginate matrix, thereby resulting in outstanding piezoelectric property, including high piezoelectric constant (7.2 pC/N) and high piezoelectric sensitivity (1.97 mV/kPa). The Gly-Alg-Glycerol film exhibited superior flexibility, enabling complex shape-shifting, e.g. origami pigeon, 40% tensile strain, and repeated bending and folding deformation without fracture. In vitro, the flexible Gly-Alg-Glycerol film sensor could detect subtle pulse signal, sound wave and recognize shear stress applied from different directions. In addition, we have demonstrated that the Gly-Alg-Glycerol film sensor sealed by polylactic acid and beeswax could serve as an in vivo sensor to monitor physiological pressure signals such as heartbeat, respiration and muscle movement. Finally, the Gly-Alg-Glycerol film possessed good biocompatibility, supporting the attachment and proliferation of rat mesenchymal stromal cells, and biodegradability, thereby showing great potential as biodegradable piezoelectric biomaterials for biomedical sensing applications.

Environmental efficacy of polyethylene microplastics: Enhancing the solidification of CuO nanoparticles and reducing the physiological toxicity to peanuts.

Microplastics and metal-based nanoparticles (NPs) are environmental pollutants that have attracted significant attention. However, there have been relatively few studies on the combined pollution of these substances in the soil-plant system. To investigate the environmental impact and interaction mechanisms of these two pollutants, a pot experiment was conducted to examine the effects of soil exposure on peanut growth. The experiment results revealed that polyethylene (PE) had a minimal effect on peanut growth, while CuO NPs significantly inhibited peanut growth. Peanut biomass decreased by over 50 % in all Cu treatments. The presence of PE significantly impacted the dissolution and absorption of CuO NPs. When 0.5 % PE was present, the dissolution and transformation of CuO NPs were limited, resulting in a total Cu concentration of 458 mg/kg. Conversely, when 5 % PE was present, the dissolution and transformation of CuO NPs were promoted, leading to a DTPA-Cu concentration of 141 mg/kg, the highest level observed. The distribution of trace elements in peanut stems also responded to the differences in Cu concentration. Both pollutants significantly disrupted soil bacteria, with CuO NPs having a more pronounced effect than PE. Throughout the entire growth cycle of peanuts, no chemical adsorption occurred between PE and CuO NPs, and CuO NPs had no significant impact on the aging rate of PE. In summary, this study provides insights into the environmental impact and transport mechanisms of composite pollution involving microplastics and metal-based nanoparticles in the soil-peanut system.

Drug exposure and treatment outcomes in patients with multidrug resistant tuberculosis and diabetes mellitus: A multicenter prospective cohort study from China.

BACKGROUND: The management of multidrug-resistant tuberculosis (MDR-TB) remains challenging. Treatment outcome is influenced by multiple factors, the specific roles of diabetes and glycemic control remain uncertain. This study aims to assess the impact of glycemic control on drug exposure, to investigate the association between drug exposure and treatment outcomes, and to identify clinically-significant thresholds predictive of treatment outcome, among patients with diabetes. METHODS: This multicenter prospective cohort study involved patients with confirmed MDR-TB and diabetes. Drug exposure level was estimated by noncompartmental analysis. The minimum inhibitory concentrations were determined for the individual Mycobacterium tuberculosis isolates. The influence of poor glycemic control (hemoglobin A1c ≥ 7%) on drug exposure and the associations between drug exposure and treatment outcome were evaluated by univariate and multivariate analysis. Classification and regression tree analysis was used to identify the drug exposure/susceptibility thresholds. RESULTS: Among the 131 diabetic participants, 43 (32.8%) exhibited poor glycemic control. Poor glycemic control was independently associated with decreased exposure to moxifloxacin, linezolid, bedaquiline, and cycloserine, but not clofazimine. Additionally, a higher ratio of drug exposure to susceptibility was found to be associated with a favorable MDR-TB treatment outcome. Thresholds predictive of 6-month culture conversion and favorable outcome were bedaquiline AUC/MIC ≥ 245 and moxifloxacin AUC/MIC ≥ 67, demonstrating predictive accuracy in patients, regardless of their glycemic control status. CONCLUSIONS: Glycemic control and optimal TB drug exposure are associated with improved treatment outcomes. This dual management strategy should be further validated in randomized controlled trials of patients with MDR-TB and diabetes.

Determination of 13 potential anti-obesity agents in hair by dispersive liquid-liquid microextraction-assisted UHPLC-MS/MS.

As the adulteration of dietary supplements with synthetic drugs remains a prevalent issue, the inclusion of anti-obesity agents may pose health risks, potentially leading to central nervous system or cardiovascular diseases. However, surveillance studies on the use of anti-obesity agents by the Chinese population are limited. This study aims to establish an efficient and rapid hair pretreatment method using dispersive liquid-liquid microextraction (DLLME) combined with high-speed grinding and develop a sensitive and accurate analytical method employing ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for detecting 13 potential anti-obesity agents in hair samples. Herein, hair samples were washed sequentially with 0.1% sodium dodecyl sulfate (SDS), water and acetone, and then ground at high speed using 1 mL of an extraction solution (internal standard solution-n-butanol-1.2 mol/L Na2HPO4, pH10.0, 100:400:500, v/v/v for procaterol; internal standard solution-ethyl acetate-1.2 mol/L Na2HPO4, pH8.0, 100:300:600, v/v/v for other 12 anti-obesity agents) while simultaneously performing DLLME. The developed method successfully detected 13 anti-obesity agents within 11 min, including bambuterol, clenbuterol, ractopamine, clorprenaline, formoterol, salbutamol, terbutaline, procaterol, phentermine, bupropion, sibutramine, desmethyl sibutramine, and N,N-didesmethyl sibutramine, which improved the screening efficiency. The calibration curves exhibited good linearity of 0.025-5 ng/mg, achieving correlation coefficients of r ≥ 0.99. The lower limits of quantification (LLOQs) for the analytes were 0.025 ng/mg, demonstrating acceptable levels of accuracy and precision. Recovery rates ranged between 73.30% and 107.47% across the three concentrations of 0.075, 0.375, and 3.75 ng/mg. The validated method was successfully applied to 369 real cases and detected six analytes, including bambuterol, salbutamol, terbutaline, sibutramine, desmethyl sibutramine, and N,N-didesmethyl sibutramine. This method offers several advantages, including simple pretreatment, high extraction efficiency, rapid extraction, solvent economy, and pollution mitigation, making it highly suitable for large-scale surveillance of usage of added anti-obesity agents.

A versatile economic strategy by HPLC-CAD for quantification of structurally diverse markers in quality control of Shengmai Formula from raw materials to preparations.

BACKGROUND: Shengmai Formula (SMF), a classic formula in treating Qi-Yin deficiency, is composed of Ginseng Radix et Rhizoma Rubra (GRR), Ophiopogon Radix (OR), and Schisandra chinensis Fructus (SC), and has been developed into various dosage forms including Shengmai Yin Oral Liquid (SMY), Shengmai Capsules (SMC), and Shengmai Injection (SMI). The pharmacological effects of compound Chinese medicine are attributed to the integration of multiple components. Yet the quality criteria of SMF are limited to monitoring schisandrol A or ginsenosides Rg1 and Re, but none for OR. Since the complexity of raw materials and preparations, establishing a economical and unified method for SMF is challenging. It is urgent to simultaneously quantify multiple components with different structures using a universal method for quality control of SMF. Charged aerosol detector (CAD) overcame the above shortcomings owing to its characteristics of high responsiveness, nondiscrimination, and low cost. PURPOSE: We aimed to establish a versatile analysis strategy using HPLC-CAD for simultaneously quantifying the structurally diverse markers in quality control of SMF from raw materials to preparations. METHOD: By optimizing the column, mobile phase, column temperature, flow rate, and CAD parameters, a HPLC-CAD method that integrated multi-component characterization, authenticity identification, transfer information of raw materials and quantitative determination of Shengmai preparations was established. RESULTS: In total 50 components from SMF were characterized (28 in GRR, 13 in SC, and 9 in OR). The differences in raw materials between species of SC and Schisandrae sphenantherae Fructus (SS), processing methods of Ginseng Radix (GR) and GRR, and locations of OR from Sichuan (ORS) and Zhejiang (ORZ) were compared. Fourteen components in 19 batches of SMY, SMC and SMI from different manufacturers were quantified, including 11 ginsenosides and 3 lignans. The multivariate statistical analysis results further suggested that Rb1, Rg1 and Ro were the main differences among Shengmai preparations. CONCLUSION: The established versatile analysis strategy based on HPLC-CAD was proven sensitive, simple, convenient, overcoming the discriminatory effect of UV detector, revealing the composition and transfer information of SMF and applicable for authentication of the ingredient herbs and improving the quality of Shengmai preparations.

Genome folding principles uncovered in condensin-depleted mitotic chromosomes.

During mitosis, condensin activity is thought to interfere with interphase chromatin structures. To investigate genome folding principles in the absence of chromatin loop extrusion, we codepleted condensin I and condensin II, which triggered mitotic chromosome compartmentalization in ways similar to that in interphase. However, two distinct euchromatic compartments, indistinguishable in interphase, emerged upon condensin loss with different interaction preferences and dependencies on H3K27ac. Constitutive heterochromatin gradually self-aggregated and cocompartmentalized with facultative heterochromatin, contrasting with their separation during interphase. Notably, some cis-regulatory element contacts became apparent even in the absence of CTCF/cohesin-mediated structures. Heterochromatin protein 1 (HP1) proteins, which are thought to partition constitutive heterochromatin, were absent from mitotic chromosomes, suggesting, surprisingly, that constitutive heterochromatin can self-aggregate without HP1. Indeed, in cells traversing from M to G1 phase in the combined absence of HP1α, HP1ß and HP1γ, constitutive heterochromatin compartments are normally re-established. In sum, condensin-deficient mitotic chromosomes illuminate forces of genome compartmentalization not identified in interphase cells.

Rapid detection of IDH mutations in gliomas by intraoperative mass spectrometry.

The development and performance of two mass spectrometry (MS) workflows for the intraoperative diagnosis of isocitrate dehydrogenase (IDH) mutations in glioma is implemented by independent teams at Mayo Clinic, Jacksonville, and Huashan Hospital, Shanghai. The infiltrative nature of gliomas makes rapid diagnosis necessary to guide the extent of surgical resection of central nervous system (CNS) tumors. The combination of tissue biopsy and MS analysis used here satisfies this requirement. The key feature of both described methods is the use of tandem MS to measure the oncometabolite 2-hydroxyglutarate (2HG) relative to endogenous glutamate (Glu) to characterize the presence of mutant tumor. The experiments i) provide IDH mutation status for individual patients and ii) demonstrate a strong correlation of 2HG signals with tumor infiltration. The measured ratio of 2HG to Glu correlates with IDH-mutant (IDH-mut) glioma (P < 0.0001) in the tumor core data of both teams. Despite using different ionization methods and different mass spectrometers, comparable performance in determining IDH mutations from core tumor biopsies was achieved with sensitivities, specificities, and accuracies all at 100%. None of the 31 patients at Mayo Clinic or the 74 patients at Huashan Hospital were misclassified when analyzing tumor core biopsies. Robustness of the methodology was evaluated by postoperative re-examination of samples. Both teams noted the presence of high concentrations of 2HG at surgical margins, supporting future use of intraoperative MS to monitor for clean surgical margins. The power of MS diagnostics is shown in resolving contradictory clinical features, e.g., in distinguishing gliosis from IDH-mut glioma.

SIRT1 exerts protective effects by inhibiting endoplasmic reticulum stress and NF-κB signaling pathways.

Silent information regulator two homolog 1 (SIRT1), an NAD + -dependent histone deacetylase, plays a pivotal regulatory role in a myriad of physiological processes. A growing body of evidence suggests that SIRT1 can exert protective effects in metabolic disorders and neurodegenerative diseases by inhibiting endoplasmic reticulum (ER) stress and the nuclear factor-κB (NF-κB) inflammatory signaling pathway. This review systematically elucidates the molecular mechanisms and biological significance of SIRT1 in regulating ER stress and the NF-κB pathway. On one hand, SIRT1 can deacetylate key molecules in the ER stress pathway, such as glucose-regulated protein 78 (GRP78), X-box binding protein 1 (XBP1), PKR-like ER kinase (PERK), inositol-requiring enzyme 1α (IRE1α), and activating transcription factor 6 (ATF6), thereby alleviating ER stress. On the other hand, SIRT1 can directly or indirectly remove the acetylation modification of the NF-κB p65 subunit, inhibiting its transcriptional activity and thus attenuating inflammatory responses. Through these mechanisms, SIRT1 can ameliorate insulin resistance in metabolic diseases, exert cardioprotective effects in ischemia-reperfusion injury, and reduce neuronal damage in neurodegenerative diseases. However, it is important to note that while these findings are promising, the complex nature of the biological systems involved warrants further investigation to fully unravel the intricacies of SIRT1's regulatory mechanisms. Nevertheless, understanding the regulatory mechanisms of SIRT1 on ER stress and the NF-κB pathway is of great significance for expanding our knowledge of the pathogenesis of related diseases and exploring new preventive and therapeutic strategies targeting SIRT1.

Borneol acts as an adjuvant agent to enhance the oral absorption of Panax notoginseng saponins in rats: Effect of optical configuration and compatibility ratios.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax notoginseng saponins (PNS), as the main active component of Panax notoginseng, shows broad pharmacological effects but with low oral bioavailability. Borneol (BO) is commonly used as an adjuvant drug in the field of traditional Chinese medicine, which has been proven to facilitate the absorption of ginsenosides such as Rg1 and Rb1 in vivo. The presence of chiral carbons has resulted in three optical isomers of BO commercially available in the market, all of which are documented by national standards. AIM OF THE STUDY: This study aimed to investigate the role of BO in promoting the oral absorption of PNS from the perspective of optical configuration and compatibility ratios. MATERIALS AND METHODS: In this study, an ultra-performance liquid chromatography coupled with triple quadrupole-linear ion trap tandem mass spectrometry (UPLC-QTRAP-MS/MS) method was validated and applied to determine the concentrations of five main saponins in PNS in rat plasma. The kinetic characteristics of PNS were compared when co-administered with BO based on optical isomerism and different compatibility ratios. RESULTS: The results showed that BO promoted the exposure of PNS in rats. Three forms of BO, namely d-borneol (DB), l-borneol (LB), and synthetic borneol (SB), exhibited different promotion strengths. SB elevated PNS exposure in rats more than DB or LB. It is also interesting to note that under different compatibility ratios, SB can exert a strong promoting effect only when PNS and BO were combined in a 1:1 ratio (PNS 75 mg/kg; BO 75 mg/kg). As a pharmacokinetic booster, the dosage of BO is worthy of consideration and should follow the traditional medication principles of Chinese medicine. CONCLUSIONS: This study shed new light on the compatible use of PNS and BO from the perspective of "configuration-dose-influence" of BO. The results provide important basis for the clinical application and selection of BO.

Sensor Head Temperature Distribution Reconstruction of High-Precision Gravitational Reference Sensors with Machine Learning.

Temperature fluctuations affect the performance of high-precision gravitational reference sensors. Due to the limited space and the complex interrelations among sensors, it is not feasible to directly measure the temperatures of sensor heads using temperature sensors. Hence, a high-accuracy interpolation method is essential for reconstructing the surface temperature of sensor heads. In this study, we utilized XGBoost-LSTM for sensor head temperature reconstruction, and we analyzed the performance of this method under two simulation scenarios: ground-based and on-orbit. The findings demonstrate that our method achieves a precision that is two orders of magnitude higher than that of conventional interpolation methods and one order of magnitude higher than that of a BP neural network. Additionally, it exhibits remarkable stability and robustness. The reconstruction accuracy of this method meets the requirements for the key payload temperature control precision specified by the Taiji Program, providing data support for subsequent tasks in thermal noise modeling and subtraction.

Dissolution-Induced Surface Reconstruction of Ni0.95 Pt0.05 Si/p-Si Photocathode for Efficient Photoelectrochemical H2 Production.

Metal silicide/Si photoelectrodes have demonstrated significant potential for application in photoelectrochemical (PEC) water splitting to produce H2 . To achieve an efficient and economical hydrogen evolution reaction (HER), a paramount consideration lies in attaining exceptional catalytic activity on the metal silicide surface with minimal use of noble metals. Here, this study presents the design and construction of a novel Ni0.95 Pt0.05 Si/p-Si photocathode. Dopant segregation is used to achieve a Schottky barrier height as high as 1.0 eV and a high photovoltage of 420 mV. To achieve superior electrocatalytic activity for HER, a dissolution-induced surface reconstruction (SR) strategy is proposed to in situ convert surface Ni0.95 Pt0.05 Si to highly active Pt2 Si. The resulting SR Ni0.95 Pt0.05 Si/p-Si photocathode exhibits excellent HER performance with an onset potential of 0.45 V (vs RHE) and a high maximum photocurrent density of 40.5 mA cm-2 and a remarkable applied bias photon-to-current efficiency (ABPE) of 5.3% under simulated AM 1.5 (100 mW cm-2 ) illumination. The anti-corrosion silicide layer effectively protects Si, ensuring excellent stability of the SR Ni0.95 Pt0.05 Si/p-Si photoelectrode. This study highlights the potential for achieving efficient PEC HER using bimetallic silicide/Si photocathodes with reduced Pt consumption, offering an auspicious perspective for the cost-effective conversion of solar energy to chemical energy.

Insect cuticle-inspired design of sustainably sourced composite bioplastics with enhanced strength, toughness and stretch-strengthening behavior.

Insect cuticles that are mainly made of chitin, chitosan and proteins provide insects with rigid, stretchable and robust skins to defend harsh external environment. The insect cuticle therefore provides inspiration for engineering biomaterials with outstanding mechanical properties but also sustainability and biocompatibility. We herein propose a design of high-performance and sustainable bioplastics via introducing CPAP3-A1, a major structural protein in insect cuticles, to specifically bind to chitosan. Simply mixing 10w/w% bioengineered CPAP3-A1 protein with chitosan enables the formation of plastics-like, sustainably sourced chitosan/CPAP3-A1 composites with significantly enhanced strength (∼90 MPa) and toughness (∼20 MJ m -3), outperforming previous chitosan-based composites and most synthetic petroleum-based plastics. Remarkably, these bioplastics exhibit a stretch-strengthening behavior similar to the training living muscles. Mechanistic investigation reveals that the introduction of CPAP3-A1 induce chitosan chains to assemble into a more coarsened fibrous network with increased crystallinity and reinforcement effect, but also enable energy dissipation via reversible chitosan-protein interactions. Further uniaxial stretch facilitates network re-orientation and increases chitosan crystallinity and mechanical anisotropy, thereby resulting in stretch-strengthening behavior. In general, this study provides an insect-cuticle inspired design of high-performance bioplastics that may serve as sustainable and bio-friendly materials for a wide range of engineering and biomedical application potentials.

Specific GAG ratios in the diagnosis of mucopolysaccharidoses.

Mucopolysaccharidoses (MPS) screening is tedious and still performed by analysis of total glycosaminoglycans (GAG) using 1,9-dimethylmethylene blue (DMB) photometric assay, although false positive and negative tests have been reported. Analysis of differentiated GAGs have been pursued classically by gel electrophoresis or more recently by quantitative LC-MS assays. Secondary elevations of GAGs have been reported in urinary tract infections (UTI). In this manuscript, we describe the diagnostic accuracy of urinary GAG measurements by LC-MS for MPS typing in 68 untreated MPS and mucolipidosis (ML) patients, 183 controls and 153 UTI samples. We report age-dependent reference values and cut-offs for chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS) and keratan sulfate (KS) and specific GAG ratios. The use of HS/DS ratio in combination to GAG concentrations normalized to creatinine improves the diagnostic accuracy in MPS type I, II, VI and VII. In total 15 samples classified to the wrong MPS type could be correctly assigned using HS/DS ratio. Increased KS/HS ratio in addition to increased KS improves discrimination of MPS type IV by excluding false positives. Some samples of UTI patients showed elevation of specific GAGs, mainly CS, KS and KS/HS ratio and could be misclassified as MPS type IV. Finally, DMB photometric assay performed in MPS and ML samples reveal four false negative tests (sensitivity of 94%). In conclusion, specific GAG ratios in complement to quantitative GAG values obtained by LC-MS enhance discrimination of MPS types. Exclusion of patients with UTI improve diagnostic accuracy in MPS IV but not in other types.

Low-concentration exogenous 3-indoleacetic acid improves fruit-setting rate of Marsdenia tenacissima by inhibiting the expression of embryo abortion-related genes.

Marsdenia tenacissima is a medicinal plant characterized by many flowers, few fruits, and a low fruit-setting rate. Exogenous auxins can improve the fruit-setting rate of plants; however, their impacts on M. tenacissima and regulatory mechanisms remain unclear. In this study, we conducted a field experiment to determine the fruit-setting rate, seed-setting rate, fruit size, and changes in transcriptional expression of related genes by spraying 10 and 50 mg·L-1 of 3-indoleacetic acid (IAA). The control plants were sprayed with distilled water. Our results indicated that the fruit-setting rate was 0.15 when treated with 10 mg·L-1 of IAA, which was 2.76-fold higher than that of the control. Compared with that of the control, the number of differentially expressed genes (DEGs) regulated by 10 mg·L-1 of IAA was 28.6-fold higher than that regulated by 50 mg·L-1 of IAA. These DEGs were closely related to hormone metabolism and fruit development. By transcriptome analysis, spraying 10 mg·L-1 of IAA increased the expressions of STP6, MYB17, and LAX3 and reduced those of CXE18, ILR1-like 3, and SAUR50; this possibly affected the ovule, embryo, and fruit development, thereby elevating the fruit-setting rate of M. tenacissima. Our results indicated that low IAA concentration increased the fruit-setting rate of M. tenacissima, providing theoretical and practical support for promoting the seed yield of M. tenacissima.

Fulvic acid modified ZnO nanoparticles improve nanoparticle stability, mung bean growth, grain zinc content, and soil biodiversity.

Zinc oxide nanoparticles (ZnO NPs) have emerged as a novel solution to combat Zn deficiency in agriculture. However, challenges persist regarding their Zn utilization efficiency and environmental impact. Fulvic acid (FA), as a relatively mature modified material, is a promising candidate to enhance the environmental stability of ZnO NPs. This study investigates modifying ZnO NPs with FA to improve their stability and increase Zn content in mung bean fruit and explores their effect on plants and the soil ecosystem. We combined FA and ZnO NPs (FZ-50) at mass ratios of 1: 5, 1: 2, and 4: 5, denoted as 20 % FZ, 50 % FZ, and 80 % FZ, respectively. Initial germination tests revealed that the 50 % FZ treatment improved sprout growth and Zn content and minimized agglomeration the most. A subsequent pot experiment compared FZ-50 with ZnO, ZnO NPs, and F + Z (1: 1 FA: ZnO NPs). Notably, the FZ-50 treatment (50 % FZ applied to the soil) demonstrated superior results, exhibiting a 30.25 % increase in yield, 121 % improvement in root nodule quality, and 56.38 % increase in Zn content, with no significant changes in enzyme activities (catalase and peroxidase). Furthermore, FZ-50 increased soil available Zn content and promoted soil microorganism diversity, outperforming ZnO and ZnO NPs. This study underscores the potential of FA as a relatively mature material for modifying ZnO NPs to increase grain Zn content, presenting a novel approach to addressing Zn deficiency in agriculture.

Second-line antituberculosis drug exposure thresholds predictive of adverse events in multidrug-resistant tuberculosis treatment.

OBJECTIVES: This study aimed to investigate the association between drug exposure and adverse events (AEs) during the standardized multidrug-resistant tuberculosis (MDR-TB) treatment, as well as to identify predictive drug exposure thresholds. METHODS: We conducted a prospective, observational multicenter study among participants receiving standardized MDR-TB treatment between 2016 and 2019 in China. AEs were monitored throughout the treatment and their relationships to drug exposure (e.g., the area under the drug concentration-time curve from 0 to 24 h, AUC0-24 h) were analyzed. The thresholds of pharmacokinetic predictors of observed AEs were identified by boosted classification and regression tree (CART) and further evaluated by external validation. RESULTS: Of 197 study participants, 124 (62.9%) had at least one AE, and 15 (7.6%) experienced serious AEs. The association between drug exposure and AEs was observed including bedaquiline, its metabolite M2, moxifloxacin and QTcF prolongation (QTcF >450 ms), linezolid and mitochondrial toxicity, cycloserine and psychiatric AEs. The CART-derived thresholds of AUC0-24 h predictive of the respective AEs were 3.2 mg·h/l (bedaquiline M2); 49.3 mg·h/l (moxifloxacin); 119.3 mg·h/l (linezolid); 718.7 mg·h/l (cycloserine). CONCLUSIONS: This study demonstrated the drug exposure thresholds predictive of AEs for key drugs against MDR-TB treatment. Using the derived thresholds will provide the knowledge base for further randomized clinical trials of dose adjustment to minimize the risk of AEs.

Recombinant expression and immune function analysis of C-reactive protein (CRP) from Hexagrammos otakii.

C-reactive protein (CRP) belongs to the short-chain pentraxin family and functions as a soluble pattern recognition molecule (PRM) aiding in host defense against pathogens. In the present study, a CRP gene, designated HoCRP, was cloned from Hexagrammos otakii for the first time. The full length of the HoCRP cDNA sequence is 821 bp, which contains an open reading frame (ORF) of 675 bp encoding a 224 amino acid protein. The deduced protein is predicted to have a theoretical isoelectric point (pI) of 5.30 and a molecular weight of 25.4 kDa. The recombinant HoCRP protein (rHoCRP) was expressed in E. coli to further characterize the functions of HoCRP. Saccharide binding experiments demonstrated that rHoCRP exhibited a high affinity for various pathogen-associated molecular patterns (PAMPs). Furthermore, bacterial binding and agglutination assays indicated that rHoCRP had the capability to recognize a wide spectrum of microorganisms. These findings suggest that HoCRP functions not only as a PRM for binding PAMPs but also as an immune effector molecule. Considering the role CRP plays in the classical complement pathway, the interaction between rHoCRP and rHoC1q was assessed and proven by a Pull-down and Elisa assay, which implied that rHoCRP may be able to activate complement. In addition, phagocytosis enhancement by rHoCRP in the presence or absence of complement components was analysed by flow cytometry. The results showed that rHoCRP could synergistically enhance the phagocytosis of RAW264.7 cells with complement, providing further evidence of complement activation by rHoCRP through the opsonization of specific complement components. In summary, our findings suggest that rHoCRP may play a crucial role in host antibacterial defense by recognizing pathogens, activating the complement system, and enhancing macrophage function.