Characteristics of dissolved organic matter during the cyanobacterial degradation in Chaohu Lake, China.

The actual DOM in Chaohu Lake was used to feed cyanobacterial to explore the changes of microbial communities, fluorescence spectral characteristics and molecular composition of DOM during the degradation of cyanobacteria. It is found that cyanobacterial grow periodically depending on the concentration of nutrients with the decreasing concentration of nutrient salts. Both Bacteroidetes and Actinobacteria have strong correlation with algae growth. Bacteroidetes has a positive correlation with algae growth, relationship on the contrary, Actinobacteria has a negative relationship. The humus-like components in the four groups are similar, but the protein-like component (C3) shows periodic changes with the life process of cyanobacteria. The average molecular weight of each sample detected by Orbitrap high-resolution mass spectrometer increases slightly and the DOM increase aromaticity in the end. In this study, the molecule of Carboxyl-Rich Alicyclic Molecules (CRAM) is difficult to be done by photodegradation and biodegradation in the early periods, but some molecules of CRAM are selectively degraded by microorganisms in the final period. The growth of cyanobacterial lead to increasing the concentration of protein-like and carbohydrate-like molecule of DOM in the water. In the final stage, the molecule group of CHO disappear significantly and the molecule group of heteroatomic group increase.

Safety, tolerability, pharmacokinetics and effects of diet on AD16, a novel neuroinflammatory inhibitor for Alzheimer's disease: a randomized phase 1 study.

BACKGROUND: AD16 is a Class 1.1 new drug candidate for Alzheimer's disease (AD), which has demonstrated potential benefits in AD by reducing neuroinflammation in preclinical studies. Herein, the pharmacokinetics (PK), safety, and tolerability of single and multiple-dose AD16 and the effect of food were assessed in healthy Chinese adults. METHODS: Single-center, randomized, placebo-controlled, double-blind studies were conducted for single and multiple ascending doses. A total of 62 subjects were enrolled in single-dose groups; 10 each in 5, 10, 20, 30, and 40 mg groups, and 6 each in 60 and 80 mg dose groups. Twenty subjects were divided equally into 30 and 40 mg groups for the multiple-dose study. To determine the effect of a high-fat diet on AD16, 16 subjects were administered a single 20 mg dose of AD16 under the fasted and fed condition in a single-center, randomized, open-label, two-cycle, two-crossover study. Moreover, safety and PK parameters were also assessed. RESULTS: Plasma exposure to a single oral dose of AD16 increased at an approximate dose-increasing rate. The pharmacodynamic dose of the AD16 can be maintained through the accumulation effect of the drug within the safety window. Compared to fasting, ingesting a high-fat meal decelerated the rate of AD16 absorption, albeit without effect on its overall absorption. No dose-related toxicities were seen in any of the studies, all treatment-emergent adverse events were grade I/II, and no serious adverse event occurred. CONCLUSIONS: The present study exhibited favorable safety, tolerability, and PK profile of AD16, supporting its further research as a potential drug treatment for AD. TRIAL REGISTRATION: ClinicalTrials.gov; NCT05787028, NCT05787041, NCT05806177. The SAD and FE studies were retrospectively registered on 28 March 2023. The MAD study was retrospectively registered on 10 April 2023.

Pharmacokinetics, bioequivalence and safety of two formulations of ticagrelor in healthy Chinese subjects: Effects of food.

Ticagrelor is the first reversible ADP P2Y12 receptor antagonist approved to treat acute coronary syndrome. To investigate the effects of food on the pharmacokinetics (PK), bioequivalence and safety of ticagrelor tablets in healthy Chinese volunteers, 32 healthy subjects were randomly assigned to an open-labelled, single-centre, two-preparation, two-sequence, two-cycle, double-crossover trial under fasting and fed conditions, with a washout period of 7 days. Plasma concentrations of ticagrelor and AR-C124910XX were determined using LC-MS/MS. The Cmax , AUC0-t and AUC0-∞ of the reference and test tablets were determined using ANOVA and the USFDA bioequivalence statistical criterion of 90% CI for the 80%-125% range (p ≤ 0.05) of the geometric mean ratios. Adverse events (AEs) were observed and recorded. Food consumption increased the AUC0-t and AUC0-∞ (p < 0.01) of ticagrelor, lowered the Cmax (p < 0.01) and prolonged the t12z (p < 0.05) of AR-C124910XX. The effects of food on the reference preparations were comparable. Formulation, time and sequence had no significant effects on the PK parameters (p â‰§ 0.05). The test formulation was bioequivalent to the reference formulation as the geometric mean ratios under fasting and fed conditions were within equivalence limits (80%-125%). No serious AEs were reported. Thus, test and reference ticagrelor are bioequivalent in Chinese subjects under fasting and fed conditions.

Risk factors of diabetic foot ulcer in patients with type 2 diabetes: a retrospective cohort study.

The aim of this study is to investigate the risk factors of diabetic foot ulcer (DFU) in patients with Type 2 diabetes. Baseline characteristics of DFU-free patients with Type 2 diabetes were retrospectively collected and DFU was identified during the follow-up. Incidence of DFU was calculated and cumulative incidence was estimated by Kaplan-Meier method. Cox regression model was used to explore factors associated with DFU. A total of 980 patients were included with a median follow-up time of 28.7 months. 259 (26.4%) patients developed DFU with an incidence rate of 11.3 per 100 person-years. The cumulative incidences of DFU at 1 year and 2 years during the follow-up were 5.4% (95% CI 3.9-6.9%) and 14.1% (95% CI 11.7-16.5%), respectively. Cox regression analysis indicated that factors associated with developing DFU included age (hazard ratio (HR)=1.06, 95% CI 1.05-1.07, per 1-year increase), body mass index (HR=1.05, 95% CI 1.02-1.07), higher level of education (HR=0.77, 95% CI 0.60-0.98), hypertension (HR=1.90, 95% CI 1.47-2.45), hyperlipidemia (HR=2.63, 95% CI 2.02-3.43), coronary heart disease (HR=2.88, 95% CI 2.22-3.75), heart failure (HR=2.47, 95% CI 1.91-3.20), stroke (HR=2.44, 95% CI 1.86-3.19), diabetic retinopathy (HR=1.86, 95% CI 1.40-2.48), diabetic kidney disease (HR=1.89, 95% CI 1.41-2.53), diabetic neuropathy (HR=1.73, 95% CI 1.31-2.30), poor glycemic control (HR=1.13, 95% CI 1.07-1.19, per 1% glycosylated hemoglobin increase), and course of diabetes (HR=1.01, 95% CI 1.00-1.01, per 1-month increase). The results showed a relatively high incidence of DFU, and revealed several baseline characteristics identified as risk factors of developing DFU.

The effect of vacuum sealing drainage after early woundabrasion on wound healing in diabetic patients with deep second degree burn and its influence on the inflammatory response.

OBJECTIVE: To investigate the effect of vacuum sealing drainage (VSD) after early woundabrasion (WA) in diabetic patients with deep second degree burn (DSDB). METHODS: This prospective study selected 89 diabetic patients with DSDB treated in our hospital. Using the random number table method, the patients were divided into the control group (44 cases with conventional treatment after early WA) and observation group (45 cases with VSD treatment after WA). Wound healing, fungal infection rate, serum levels of inflammatory factors and vascular endothelial growth factor (VEGF), and adverse reactions in both groups were compared. RESULTS: After 2 weeks of treatment, the total effective rate of observation group was higher than that of control group, and the incidence of adverse reactions showed an opposite trend (both P<0.05). Compared with the control group, the wound healing time was shortened, the wound healing rate was increased, and the fungal infection rate was decreased in the observation group (all P<0.05). Compared with before treatment, serum TNF-α levels in both groups were decreased, while serum levels of IL-10, IL-4 and VEGF were increased after treatment, and the changes in the observation group were more obvious (all P<0.05). CONCLUSIONS: In diabetic patients with DSDB, VSD after early WA can effectively reduce the incidence of fungal infection, reduce inflammation, improve VEGF level, and facilitate wound healing.

Adaptive Locomotion Control of a Hexapod Robot via Bio-Inspired Learning.

In this paper, an adaptive locomotion control approach for a hexapod robot is proposed. Inspired from biological neuro control systems, a 3D two-layer artificial center pattern generator (CPG) network is adopted to generate the locomotion of the robot. The first layer of the CPG is responsible for generating several basic locomotion patterns and the functional configuration of this layer is determined through kinematics analysis. The second layer of the CPG controls the limb behavior of the robot to adapt to environment change in a specific locomotion pattern. To enable the adaptability of the limb behavior controller, a reinforcement learning (RL)-based approach is employed to tune the CPG parameters. Owing to symmetrical structure of the robot, only two parameters need to be learned iteratively. Thus, the proposed approach can be used in practice. Finally, both simulations and experiments are conducted to verify the effectiveness of the proposed control approach.

[Characteristics of Nitrogen and Phosphorus Losses and Runoff in a Typical Purple Soil Watershed in the Three Gorges Reservoir Area].

To understand the runoff pollution characteristics of the typical purple soil small watershed in the Three Gorges Reservoir (TGR), the rainfall-runoff duration under typical land use types of the Xinzheng watershed and the nitrogen (N) and phosphorus (P) concentrations in the outlet runoff of each catchment were dynamically monitored, and the loss rule of N and P in the rainfall runoff in the small watershed in the TGR was investigated and analyzed. The results showed that the losses of runoff N and P were 13.69 kg·(hm2·a)-1 and 1.50 kg·(hm2·a)-1, respectively. N and P in agricultural fertilizers and rainfall scouring were the main causes of runoff pollution in the Xinzheng watershed. The average concentration of total nitrogen (TN) and total phosphorus (TP) reached 10.05 mg·L-1 and 1.10 mg·L-1, far exceeding the occurrence standard of eutrophication, which should be cause for concern. The nitrate nitrogen (NN) and particulate phosphorus (PP) in the rainfall were 69.47 kg and 6.83 kg on August 15, 2010, accounting for 53.91% and 53.78% of TN and TP, respectively. The NN and AN were 6.68 kg and 5.61 kg, respectively, in the rainfall on August 26, 2010, accounting for 37.74% and 31.69% of TN and PP was 1.36 kg, accounting for 57.63% of TP, indicating that nitrogen loss was mainly through the soluble state, while phosphorus migration was dominated by particulate matter. Heavy rainfall in the Xinzheng watershed had a significant impact on the loss of nitrogen and phosphorus. This was related to the properties of purple soil, such as thin soil layer, frequent cultivation and relatively loose soil.

Effect of dissolved organic matters on adsorption and desorption behavior of heavy metals in a water-level-fluctuation zone of the Three Gorges Reservoir, China.

Operation of recession and inundation in Three Gorges Reservoir (TGR) revealed a potential contribution to the migration of heavy metals in soil and fluvial systems, thus led to negative ecological impacts. The work herein investigated the concentration and speciation of three typical heavy metals (Cd, Cr and Cu) in a water-level-fluctuation zone of TGR, as well as simulated the adsorption and desorption behavior of heavy metals on soils, which aimed at elucidating the fate of heavy metals in this special area. Field investigation revealed that water level fluctuation greatly enabled the migration of heavy metals to inner or upper soil layers. Laboratory experiments showed that adsorption of Cd(II) was a chemical process and dissolved organic matters (DOM) in soils strengthened the combination of Cd(II) to soil surface which inhibited the desorption process. Cr(VI) was physically adsorbed and readily to be desorbed. DOM enabled deposition of Cr(VI) in soils. Cation exchange was dominate mechanism in Cu(II) adsorption process, whereas DOM presented positive effects on desorption of Cu(II). The results presented in this study would provide basic theory for scientific research in TGR.

Characteristics of organic phosphorus fractions in soil from water-level fluctuation zone by solution 31P-nuclear magnetic resonance and enzymatic hydrolysis.

Phosphorus (P) is an essential nutrient element for biological growth that can contribute to eutrophication in aquatic ecosystems. Water trophic status and algae growth are primarily related to the content of bioavailable P, which is primarily related to enzymatically hydrolysable organic P(EHOP) and dissolved inorganic P(IP). In this study, soil samples from the water-level fluctuation zone (WLFZ) were collected from a tributary of the Three Gorges Reservoir (TGR) to characterize the properties of organic P(OP) fractions using solution 31P-nuclear magnetic resonance (NMR) and enzymatic hydrolysis. 31P-NMR showed that orthophosphate was the main part of the bioavailable P in the WLFZ soil and accounted for 80.4% of the NaOH-EDTA extractable total P (NaOH-EDTA TP), while phosphate monoester accounted for 60.5% of NaOH-EDTA extractable OP (NaOH-EDTA OP). The soil properties and replenishment from the mainstream of the Yangtze River to the Pengxi River have a certain effect on the content and distribution of P forms in the WLFZ soil of the tributary. The EHOP accounted for 28.1% of the NaOH-EDTA OP, and a significant positive correlation was observed between labile monoester P and EHOP and organic matter (OM). The water-soluble OP(H2O-OP), bicarbonate-extractable OP(NaHCO3-OP), and Fe- and Al-associated OP(Fe/Al-OP) were significantly hydrolyzed by phosphatase and thus exhibited great release potential. The ranking of the bioavailability of OP was Fe/Al-OP > H2O-OP > NaHCO3-OP. Phytate-like P were mainly found in H2O-OP and NaHCO3-OP, which indicated that periodic submersion-emersion cycles promoted the release of phytate-like P from Fe/Al-OP into the water column of the TGR. These observations suggest that when the external P input was effectively controlled, a huge risk of release of the internal OP from the WLFZ soil, and the biogeochemical cycling of the bioavailable P played an important role in maintaining the eutrophication of the reservoir.

Neferine in the Lotus Plumule Potentiates the Antitumor Effect of Imatinib in Primary Chronic Myeloid Leukemia Cells In Vitro.

Imatinib, the prototype BCR-ABL tyrosine kinase inhibitor (TKI), is the first-line treatment for Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase. However, a subgroup of patients exhibit poor response or experience relapse. This issue may be overcome by combination therapy using natural compounds. Neferine, a major bisbenzylisoquinoline alkaloid extracted from "lotus plumule" (seed embryo of lotus) commonly used in traditional Chinese medicine and tea, was used herein in the combination treatment of CML. The MTT assay showed that neferine exerted cytotoxicity in primary CML cells in a dose-dependent manner. Moreover, low concentrations of neferine (4 and 8 µM) sensitized primary CML cells to imatinib (CI < 1), and significantly decreased its IC50 from 0.70 ± 0.10 to 0.32 ± 0.06 µM and 0.16 ± 0.02 µM, respectively. Cotreatment of neferine and imatinib significantly decreased the expression of BCR-ABL protein and its molecular chaperone heat shock protein 90 (Hsp90) mRNA and protein levels, and further decreased phospho-extracellular regulated protein kinase 1/2 (p-Erk1/2) and myeloid cell leukemia (Mcl-1) expression. These results suggest that neferine might be a potential imatinib sensitizer in CML treatment. PRACTICAL APPLICATION: In China, Lotus plumule, the green embryo of lotus, is used as a tea and as a source of herbal medicine in the treatment of anxiety, insomnia, spermatorrhea, and thirst. Additional, neferine, a bisbenzylisoquinoline alkaloid extracted from lotus plumule has been shown to have antitumor potential. Herein, the effect of neferine and imatinib cotreatment on primary CML cells obtained from CML patients was assessed, with a synergistic effect being observed between the two compounds. Therefore, neferine might be a promising natural compound to potentiate imatinib in CML patients.

Spatiotemporal distribution and risk assessment of organotins in the surface water of the Three Gorges Reservoir Region, China.

The water quality security of the Three Gorges Reservoir during different operating periods has been a subject of recent concern. This study is the first to report the spatiotemporal variability of organotins (OTs) in surface water under dynamic water level conditions in the Three Gorges Reservoir Region (TGRR). TGRR surface water was collected during three monitoring campaigns to analyze butyltins (BTs) and phenyltins (PTs) using a gas chromatography-mass spectrometry system. Our results showed that TGRR surface water was polluted by BTs and PTs, with mono-OTs being the dominant species. A wide range of BTs and PTs concentrations was observed across the study area, but tributyltin (TBT) displayed extensive spatial distribution, and the highest concentrations consistently occurred in the downstream region of the TGRR study area, with a maximum of 393.35 ng Sn/L in Zigui (S27). The total OTs contamination level decreased over time. The diphenyltin concentration exhibited significant seasonal variation, while other OTs showed seasonal changes only during two monitoring campaigns, with the exception of dibutyltin. An ecological risk assessment indicated that both TBT and triphenyltin posed risks to aquatic organisms in TGRR surface water. We urgently recommend continuous monitoring and further measures to prevent and control OTs pollution in the TGRR.

Identification and analysis of Triphenyltin chloride with surface enhanced Raman scattering spectroscopy.

Triphenyltin (TPhT) is a kind of organotin compounds which have been used ubiquitously as herbicide, pesticide, and fungicide in agriculture. The present study provides the possibility to detect and monitor TPhT with normal Raman spectroscopy and surface enhanced Raman scattering (SERS) spectroscopy. Firstly, the complete vibrational Raman spectra characterization of TPhT along with the IR spectroscopy were reported for the first time. Then a wide range of pH values were carried out to choose the optimal pH value in TPhT detection by using Raman spectroscopy. Afterwards, Raman spectra of various TPhT solutions were collected and analyzed. The results indicate that the optimal pH value for TPhT detection by Raman spectroscopy is 5.5, and with silver nanoparticles (Ag NPs) as SERS substrate is an effective technique for trace TPhT detection with an enhancement by 5 orders of magnitude and the detection limit can be as low as 0.6 ng/L within less than 30 s. Finally, in this study, the residual of TPhT on apple peel was investigated by casting different concentrations of TPhT on apple peel under the current optimized condition. The result demonstrates that TPhT could be detected based on its SESR spectra at 6.25 ng/cm(2) in standard solutions.

[Analysis of Endocrine Disruptor: Triphenyltin Chloride with Raman Spectroscopy].

Triphenyltin Chloride (TPhT) is one of the only two kinds of metal compounds known in the endocrine disruptors. TPhT is widely used in industry, agriculture and transportation fields, which can cause great impact on soil, marine and inland freshwater environment. This experiment collects the Raman signal of TPhT standard powders by applying laser confocal Raman spectroscopy to explore the feasibility of the method and to acquire optimized parameters. In this paper, we combined the application of laser confocal Raman spectroscopy with TPhT physical property. Due to different functional groups of TPhT molecules shows different vibration modes, the Raman spectra was divided into three wavenumber areas(1 500~3 200, 900~1 500 and 100~900 cm-1) to attribute and analyze their assignments of the Raman peaks, obtaining the characteristics of TPhT vibration modes and the corresponding characteristic peaks. Finally, a standard Raman spectra library was established with the spectral range between 100~3 200 cm-1. The results showed that the Raman spectra with high signal-to-noise ratio can be obtained in a short time when the laser power options decayed to 0.5% of the original power (500 mW) after 10s exposure and 2 times integration. Strong Raman signals observed in the Raman spectroscopy at 212, 332, 657, 997 and 1 577 cm-1 could be used as the characteristic peaks of TPhT in Raman detection. Otherwise, the co-occurrence of the Raman peaks at 657 and 997 cm-1 can be considered as the presence of TPhT in complex environmental samples. Experimental results are given to identify the presence of TPhT. The results would be used to identify the presence of TPhT residual in real environmental samples, which provide a theoretical basis and data base on Raman spectroscopy.

Enhanced nitrogen and phosphorus removal by an advanced simultaneous sludge reduction, inorganic solids separation, phosphorus recovery, and enhanced nutrient removal wastewater treatment process.

An advanced wastewater treatment process (SIPER) was developed to simultaneously decrease sludge production, prevent the accumulation of inorganic solids, recover phosphorus, and enhance nutrient removal. The feasibility of simultaneous enhanced nutrient removal along with sludge reduction as well as the potential for enhanced nutrient removal via this process were further evaluated. The results showed that the denitrification potential of the supernatant of alkaline-treated sludge was higher than that of the influent. The system COD and VFA were increased by 23.0% and 68.2%, respectively, after the return of alkaline-treated sludge as an internal C-source, and the internal C-source contributed 24.1% of the total C-source. A total of 74.5% of phosphorus from wastewater was recovered as a usable chemical crystalline product. The nitrogen and phosphorus removal were improved by 19.6% and 23.6%, respectively, after incorporation of the side-stream system. Sludge minimization and excellent nutrient removal were successfully coupled in the SIPER process.

Direct sensing of fluoride in aqueous solutions using a boronic acid based sensor.

Binding of the fluoride ion triggers aggregation of a pyreneboronic acid-catechol ensemble in acidic aqueous solutions, giving rise to intense excimer emission, allowing for sensitive fluoride ion sensing at ppm levels, with an apparent fluoride binding constant higher than 10(3) M(-1) which is unprecedented for boronic acid sensors in water.

Glucose sensing via aggregation and the use of "knock-out" binding to improve selectivity.

Aggregates of an amphiphilic monoboronic acid bearing a hydrophobic pyrene fluorophore were employed for highly modulating, sensitive, and selective ratiometric fluorescent sensing of glucose in aqueous solution. The selectivity for glucose was improved by "knock-out" binding of fructose by phenylboronic acid.

Ordered honeycomb microporous films from self-assembly of alkylated guanosine derivatives.

Ordered honeycomb microporous films have previously been fabricated from polymeric macromolecules. We report here the successful fabrication of them from the supramolecular self-assembly of small molecules, alkylated guanosine derivatives. The ribbonlike self-assembly of the guanosines in CHCl3 is found to be the intrinsic structure that forms regular microporous structure via Bénard-Maragoni convection. Factors such as substrate, solvents, guanosine concentration, and solvent evaporation temperature are revealed to be able to control the size of the formed micropores, which in turn allows for the wettability of the honeycomb film surface to be modulated. These microporous materials exhibit excellent ability of loading organic dyes that eventually leads to the fabrication of luminescent honeycomb films. As structures of both the small molecules that can assemble and their self-assemblies can be varied and controlled, extended applications of this supramolecular method are expected to lead to microporous films of interesting functions.