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It remains unclear whether dosage adjustment of intravenous lidocaine is necessary during general anesthesia for elderly patients over 75 years old. This study aimed to investigate the effects of age on the pharmacokinetics (PK) and safety of intravenous lidocaine in patients undergoing general anesthesia. A total of 599 plasma samples were collected from 76 general anesthesia patients across three age groups: 18-64, 65-74, and ≥ 75 years. Lidocaine was administered intravenously at a dose of 1.5 mg/kg for the 18-64 and 65-74 years groups, while the dose was adjusted to 1.0 mg/kg for the ≥ 75 years group. The plasma concentrations of lidocaine and its active metabolites were measured using a validated ultra-performance liquid chromatography-tandem mass spectrometry assay, and the data were analyzed using a noncompartmental analysis. The results revealed no significant age-related differences in the PK of lidocaine and its metabolites. Among the three age groups, over 90 % of patient achieved a lidocaine concentration within a safe and effective range when the dosage was normalized to 1.5 mg/kg. In conclusion, age-based dosage adjustment was unnecessary for intravenous lidocaine in patients below 86 years undergoing general anesthesia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Peptide-major histocompatibility complex (pMHC) multimers are wide recognized as the premier technique for detecting, characterizing, and isolating antigen-specific CD8 + T-cell subsets. These multimers are specifically useful in studying infections, autoimmune conditions, and cancer through single-cell analysis techniques such as flow cytometry and fluorescence microscopy. However, the development of high-throughput assays with commercially available pMHC tetramers can be expensive, while in-house production may pose challenges for most biology research laboratories. In this context, we introduce a cost-friendly and uncomplicated protocol to prepare empty MHC class I tetramers using disulfide-stabilized molecules and photolabile peptide ligands. Our method relies on disulfide bond-stabilized MHC-I molecules, which demonstrated stability when folded into stable monomers in the presence of a photolabile epitope. These monomers, upon ultraviolet irradiation and streptavidin binding, efficiently assemble into tetramers devoid of any peptide. Following a short incubation with the peptide of interest under gentle conditions, the resulting pMHC tetramer effectively detects patient-sourced, neoantigen-specific T cells. Our unique approach streamlines large-scale pMHC generation, thus paving the way for advancements in T cell-based diagnostics and personalized therapies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sheng Ye reports financial support was provided by Tianjin University. Sheng Ye reports a relationship with Tianjin University that includes: employment and travel reimbursement. Sheng Ye has patent pending to Mengyu Zhang, Qiwei Wang, Si Liu, Sheng Ye. no more If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Herpetospermum pedunculosum seeds also known as Herpetospermum caudigerum Wall. is the mature seed of the Herpetospermum pedunculosum(Ser.) C. B. Clarke,Cucurbitaceae. Modern pharmacological studies have shown that H. pedunculosum has hepatoprotective, anti-inflammatory, anti-gout and antibacterial pharmacological activities. The biologically active chemical components include lignin compounds such as Herpetin, Herpetetrone, Herpetoriol and so on. The natural product displays considerable skeletal diversity and structural complexity, offering significant opportunities for novel drug discovery. Based on the multi-omics research strategy and the 'gene-protein-metabolite' research framework, the biosynthetic pathway of terpenoids and lignans in H. pedunculosum has has been elucidated at multiple levels. These approaches provide comprehensive genetic information for cloning and identification of pertinent enzyme genes. Furthermore, the application of multi-omics integrative approaches provides a scientific means to elucidate entire secondary metabolic pathways. We investigated the biosynthetic pathways of lignin and terpene components in H. pedunculosum and conducted bioinformatics analysis of the crucial enzyme genes involved in the biosynthetic process using genomic and transcriptomic data. We identified candidate genes for six key enzymes in the biosynthetic pathway. This review reports on the current literature on pharmacological investigations of H. pedunculosum, proposing its potential as an antidiabetic agent. Moreover, we conclude, for the first time, the identification of key enzyme genes potentially involved in the biosynthesis of active compounds in H. pedunculosum. This review provides a scientific foundation for the discovery of novel therapeutic agents from natural sources., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The establishment of near infrared (NIR) spectroscopy model mostly relies on chemometrics, and spectral analysis combined with artificial intelligence (AI) provides a new way of thinking for pharmaceutical quality inspection, new algorithms such as back propagation artificial neural networks (BP-ANN) and swarm intelligence optimization algorithms such as sparrow search algorithm (SSA) provide core technical support. In order to explore the application of AI in the pharmaceutical field, in this study, Angelica dahurica formula granules with a relatively complex system were selected as the research object. Quantitative analysis models were established by using partial least squares regression (PLSR) with a micro-NIR spectrometer, and BP-ANN modeling results were compared. For the best PLSR models of six characteristic components in the continuous counter-current extract of Angelica dahurica, R 2 v of imperatorin was lower than 0.90, and the RPD values of imperatorin, phellopterin, and isoimperatorin were even lower than 1. When the prediction model established by SSA-BP-ANN was used for quantitative analysis, R 2 v of six components were all higher than 0.92, and the RPD values all higher than 1.5, which proved that the BP-ANN method was better than PLSR. This study confirmed that in the continuous counter-current extraction progress of Angelica dahurica formula granules, the use of micro-NIR spectrometer combined with AI could realize the rapid prediction of the contents of six characteristic components. The comparison results provided a scientific reference for the process analysis and on-line monitoring in the production process of traditional Chinese medicine by micro-NIR spectrometer combined with AI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

There is presently no efficient dose individualization strategy for the use of antiseizure medications in epileptic pregnant patients. This study aimed to develop a population pharmacokinetics model for levetiracetam and propose a tailored adaptive individualized dosage strategy for epileptic pregnant patients. A total of 322 levetiracetam plasma concentrations from 238 patients with epilepsy were included, including 216 women with epilepsy (20.83% of whom were pregnant). The levetiracetam plasma concentration was measured using a validated ultra-performance liquid chromatography-tandem mass spectrometry assay, and the data were modeled using a nonlinear mixed-effects model. The resultant model served as the basis for simulating the dosage adjustment strategy. A one-compartment model with first-order elimination best described the pharmacokinetic data of levetiracetam. The apparent clearance (CL/F) was 3.43 L/h (95% CI 3.30-3.56) and the apparent volume of distribution was 43.7 L (95% CI 40.4-47.0) for a typical individual of 57.2 kg. Pregnancy and body weight were found to be significant covariates of CL/F of levetiracetam. The recommended regimen of levetiracetam could be predicted by the population pharmacokinetic model based on body weight, gestational age, and the daily dose of levetiracetam taken before pregnancy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

In this work, a stable ratiometric nanofluorescent probe for the detection of 2,6-dipicolinic acid (DPA), a Bacillus anthracis biomarker, was developed based on confinement-induced emission enhancement of cationic styrylpyridine salt derivative L in MCM-22 molecular sieve pores. The cationic L and the lanthanide Tb 3+ were loaded into the pores of the molecular sieve by electrostatic interaction with the negatively charged AlO 4 tetrahedron unit, and L exhibited enhanced red fluorescence emission as a stable fluorescence reference mark in the nanoprobe platform due to the restricted molecular torsion of L in the pores of MCM-22. At the same time, the characteristic green fluorescence emission of Tb 3+ can be excited by energy transfer due to the "antenna effect" of DPA. The prepared Tb-L@MCM-22 nanoprobe showed specific selectivity and stable fluorescence ratiometric detection of DPA in tap water, lake water, bovine serum and actual bacterial spores. Benefiting from the confinement-induced fluorescence enhancement effect of L in the MCM-22 molecular sieve pores, the obtained Tb-L@MCM-22 can provide a stable reference signal for the fluorescence ratiometric detection of DPA with a limit of detection (LOD) of 78.6 nM and 1.310 × 10 4 spores per mL. More importantly, combining of the Tb-L@MCM-22 based DPA detection test strips with a smartphone app demonstrated a stable, convenient and rapid method for detecting of anthrax biomarkers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The constantly increasing amount of road vehicles causes massive exhaust emissions of pollutants, including polycyclic aromatic hydrocarbons (PAHs), necessitating a global responsibility to implement the policy of the ban on the sale of new petrol and diesel cars. Here, we assessed the policy control efficiency on marine pollution of PAHs in China through scenario modeling and prediction models, based on pollution monitoring, risk assessment, and source apportionment of PAHs in typical bays of Shandong Province. The results showed that in 2021, the pollution risk levels were relatively low (HI: 0.008-0.068, M-ERM-Q: 0.001-0.016, IBR: 1.23-2.69, ILCR: 8.11 ×10 -6 -1.99 ×10 -5 ), and PAHs were mainly derived from traffic emissions (24.9%-35.2%), coal combustion (25.2%-32.9%), petroleum (17.2%-28.9%), and biomass combustion (17.6%-22.8%). In 2050, the predicted decrease of pollution risk values after the implementation of the policy was significant (12%-26%), and the gap between 2021 and 2050 was also significantly huge (18%-85%) without considering possible substitution of conventional energy. Collectively, this study built systematic approaches for assessing prospective marine pollution of PAHs. However, due to the particularity of Shandong Province, i.e., its national predominance of conventional energy consumption, the policy may be more effective when it comes to other coastal areas worldwide, calling for a larger scale research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aflatoxin B1 (AFB1) is one of the most toxic mycotoxins prevalent in the environment and food chain, posing severe health risks to humans and animals. Bile acids are natural detergents synthesized from cholesterol and play a key role in the excretion of toxins in vertebrates. Here, pacific white shrimp (Litopenaeus vannamei) served as an animal model to examine the toxicity mechanisms of AFB1 and assess the potential alleviating effects of bile acids against AFB1. Our results revealed that AFB1 exposure significantly inhibited the growth performance and immune response of shrimp, accompanied by AFB1 accumulation and histological damage. Mechanistically, AFB1-induced DNA damage activated DNA repair mechanisms and induced the arrest of cell cycle via the ATR-cyclin B/cdc2 pathway. Additionally, AFB1 directly suppressed the immune response and growth performance of shrimp by inhibiting Toll and IMD pathways and the secretion of digestive enzymes. Notably, dietary bile acids significantly reduced AFB1 accumulation and alleviated AFB1-induced growth retardation and immunotoxicity in shrimp, and CCKAR, ATR, and Relish may be key mediators of the alleviating effects of bile acids. Our study provided new insights into the toxicity mechanisms of AFB1 in invertebrates and highlighted the potential of bile acids to alleviate AFB1 toxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In the study, a novel ENR-degrading microorganism, Microbacterium proteolyticum GJEE142 was isolated from aquaculture wastewater for the first time. The ENR removal of strain GJEE142 was reliant upon the provision of limited additional carbon source, and was adaptative to low temperature (13 ℃) and high salinity (50‰). The ENR removal process, to which intracellular enzymes made more contributions, was implemented in three proposed pathways. During the removal process, oxidative stress response of strain GJEE142 was activated and the bacterial toxicity of ENR was decreased. Strain GJEE142 could also achieve the synchronous removal of ammonium, nitrite, nitrate and phosphorus with the nitrogen removal pathways of nitrate → nitrite → ammonium → glutamine → glutamate → glutamate metabolism and nitrate → nitrite → gaseous nitrogen. The phosphorus removal was implemented under complete aerobic conditions with the assistance of polyphosphate kinase and exopolyphosphatase. Genomic analysis provided corresponding genetic insights for deciphering removal mechanisms of ENR, nitrogen and phosphorus. ENR, nitrogen and phosphorus in both actual aquaculture wastewater and domestic wastewater could be desirably removed. Desirable adaptation, excellent performance and wide distribution will make strain GJEE142 the hopeful strain in wastewater treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Persistent patent ductus arteriosus (PDA) is generally observed in preterm neonates. Oral ibuprofen is the standard treatment for closing PDA in China. To investigate the chiral pharmacokinetics of ibuprofen enantiomers in Chinese premature infants with PDA, a simple, fast, and sensitive analytical enantioselective technology was developed with ultra-performance liquid chromatography (UPLC) - tandem mass spectrometry (MS/MS). Chromatographic separation of (R)-ibuprofen and (S)-ibuprofen was accomplished on a Lux® 3 µm Cellulose-3 (150 mm × 2.0 mm, 3 μm) at a flow rate of 0.2 mL/min within 6 min. UPLC separation was achieved by isocratic elution with a mobile phase consisting of formic acid:water (75:1000000, v/v) and acetonitrile:methanol (1:1, v/v). Only 50 µL of plasma samples were pre-treated with acetonitrile precipitation. Ibuprofen-d 3 was used as an internal standard. The standard curves of both enantiomers were linear over a concentration range of 0.0500 μg/mL to 50.00 μg/mL. The method has been validated for selectivity, carryover effect, lower limit of quantification, precision, accuracy, matrix effect, extraction recovery, dilution integrity, and stability based on the existing guidelines of the National Medical Products Administration, the United States Food and Drug Administration, and the European Medicines Agency. This method has been successfully applied to investigate the pharmacokinetics of ibuprofen enantiomers in 9 preterm infants with PDA. Our results showed that a high chiral inversion ratio of (R)- to (S)-ibuprofen exists in Chinese preterm neonates. Further studies should be conducted to monitor drug concentration following oral administration of ibuprofen and to consider the effect of individual variations and ethnic differences in metabolizing enantiomers of ibuprofen in premature neonates with PDA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The general electrochemical biosensors for telomerase detection require the immobilization of primers on the electrode surface for telomeric extension and hybridization reactions. However, immobilization of primers may suffer from the challenges of hindrance effect and configuration freedom, thus reducing the extension and hybridization efficiency. Herein, we developed a sensitive electrochemical biosensor for telomerase detection by integration of homogeneous extension and hybridization reactions and surface-tethered detection. In the presence of telomerase, the biotinylated primer (bio-primer) was efficiently elongated with telomeric repeats of (TTAGGG) n at the 3' end in solution. Then, the extension product (bio-DNA) was hybridized with the signal probe DNA modified on the surface of ferrocene (Fc)-capped gold nanoparticle (AuNP). The bio-DNA/DNA/Fc-AuNP hybrids were then tethered by streptavidin-modified electrodes through the specific avidin-biotin interactions, thus producing strong electrochemical signals from the oxidation of Fc tags. The biosensor was successfully used to determine telomerase in HeLa cells and monitor the inhibition efficiency of inhibitor. A wide linear range for the detection of telomerase extracted from HeLa cells was attained. This method has great potential in clinical diagnosis and anti-cancer drug development, and should be beneficial for the fabrication of novel biosensors by integration of homogeneous catalysis and hybridization reactions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Increasingly drastic global change is expected to cause hydroclimatic changes, which will influence vegetation productivity and pose a threat to the terrestrial carbon sink. Asymmetry represents an imbalance between vegetation growth and loss of growth during dry and wet periods, respectively. However, the mechanisms of asymmetric plant responses to hydrological changes remain poorly understood. Here, we examined the spatiotemporal patterns of asymmetric responses of vegetation productivity across terrestrial ecosystems in China. We analyzed several observational and satellite-based datasets of plant productivity and several reanalyzed datasets of hydroclimatic variables from 2001 to 2020, and used a random forest model to assess the importance of hydroclimatic variables for these responses. Our results showed that the productivity of >50 % of China's vegetated areas showed a more positive asymmetry (2.3 ± 9.4 %) over the study period, which were distributed broadly in northwest China (mainly grasslands and sparse vegetation ecosystems). Negative asymmetries were most common in forest ecosystems in northeast China. We demonstrated that one-third of vegetated areas tended to exhibit significant changes in asymmetry during 2001-2020. The trend towards stronger positive asymmetry (0.95 % yr -1 ) was higher than that towards stronger negative asymmetry (-0.55 % yr -1 ), which is beneficial for the carbon sink. We further showed that in China, soil moisture was a more important driver of spatiotemporal changes in asymmetric productivity than precipitation. We identified thresholds of surface soil moisture (20-30 %, volume water content) and root-zone soil moisture (200-350 mm, equivalent water height) that were associated with changes in asymmetry. Our findings highlight the necessity of considering the dynamic responses of vegetation to hydrological factors in order to fully understand the physiological growth processes of plants and avoid the possible loss of productivity due to future climate change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A novel strain, Nitratireductor sp. GZWM139 capable of efficient removal of SMX was isolated from mariculture sewage, and Nitratireductor was reported to conduct the removal of antibiotics for the first time. Strain GZWM139 exhibited desirable adaptations to environmental factors with SMX removal efficiencies more than 90 % at temperatures of 28-38 °C, pH values of 4.5-8.5, salinities of 20-30 ‰, SMX levels of 1-5 mg/L and shaking speeds of 20-260 rpm. SMX removal was a cooperated process implemented by intracellular enzymes and extracellular enzymes, and was achieved through four proposed biotransformation pathways with the occurrences of demethylation, hydroxylation, nitration, formylation, oxidation, bond cleavage and ring opening. Strain GZWM139 responded to the SMX removal process by altering properties of cell membrane and motivating activities of xenobiotic-metabolizing enzymes and antioxidant system. Genomic analysis proved the existence of functional genes relevant to the SMX removal in strain GZWM139 and provided echoing genetic insights for revealing the SMX removal mechanism. Strain GZWM139 performed efficient detoxification of SMX and accomplished simultaneous removal of SMX and nitrogen in both mariculture sewage and domestic sewage. The findings are significant to the effective elimination of SMX pollution and comprehensive cognitions on metabolic mechanisms of SMX removal., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Lanthanide ion probes have recently been considered as promising sensing materials due to their high sensitivity and good optical properties. Herein, the 3D hierarchical lanthanide functionalized layered double hydroxides microcapsules were synthesized via a facile ion exchange strategy and further developed as novel fluorescent probes for detecting trace amounts of the anthrax biomarker dipicolinicacid (DPA). Benefiting from the 3D porous superstructure and abundant unsaturated coordination sites of lanthanide ion, the ternary Ni-Fe-Ln-LDHs (Ln = Tb/Eu) not only possess a large reactive contact area to improve the sensitivity of DPA detection, but also demonstrate very fast reaction rate. The design of inexpensive fluorescent test strips can perform the on-site and real-time detection via a smartphone with a color recognition application. More prominently, the sensitivity of the system was evaluated by actual spore samples with the detection limit as low as 3.54 × 10 4  spores/mL. The 3D lanthanide functionalized LDHs nanoprobe constructed by ion exchange exhibits a new vision for the development of a sensing platform in other research areas., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Hydroxyl radical (•OH) in fuel combustion gas seriously damages human health. The techniques for simultaneously detecting and scavenging •OH in these gases are limited by poor thermal resistance. To meet this challenge, herein, metal organic frameworks (MOFs) with high thermal stability (80-400 °C) and dual function (•OH detection and elimination) are developed by coordinating Ce ions with terephthalic acid (TA) (Ce-BDC). Due to the reversible conversion between Ce 3+ and Ce 4+ , and the high concentration of Ce 3+ on the surface of Ce-BDC MOFs (89.6%), an •OH scavenging efficiency over 90% is realized. Ratiometric fluorescence (I 440 nm /I 355 nm ) detection of •OH with a low detection limit of ∼4 μM is established by adopting Ce ions as an internal standard and TA as an •OH-responsive fluorophore. For real applications, the Ce-BDC MOFs demonstrate excellent •OH detection sensitivity and high •OH scavenging efficiency in gas produced from cigarettes, wood fiber and machine oil. Mouse model results show that the damage caused by •OH in cigarette smoke can be greatly reduced by Ce-BDC MOFs. This work provides a promising strategy for sensitively detecting and efficiently eliminating •OH in fuel combustion gas., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Sulfide generally exists in wastewater, black and odor river, as well as aquaculture water, and give rise to adverse effect on ecological stability and biological safety, due to the toxicity, corrosivity and malodor of sulfide. In the present study, a chemolithotrophic sulfide-oxidizing bacteria (SOB) was isolated and identified as Marinobacter maroccanus strain SDSWS8. And it produced no hemolysin and was susceptible to most antibiotics. There were no accumulation of sulfide, sulfate and thiosulfate during the sulfide removal process. The optimum conditions of sulfide removal were temperature 15-40 °C, initial pH value 4.5-9.5, salinity 10-40‰, C/N ratio 0-20 and sulfide concentration 25-150 mg/L. The key genes of sulfide oxidation, Sox system (soxB, soxX, soxA, soxZ, soxY, soxD, soxC), dissimilatory sulfur oxidation (dsrA, aprA and sat) and sqr, were successfully amplified and expressed, indicating the three pathways coordinated to complete the sulfide oxidation. Besides, strain SDSWS8 had inhibitory effect on four pathogen Vibrio (V. harveyi, V. parahaemolyticus, V. anguillarum and V. splendidus). Furthermore, efficient removal of sulfide from real aquaculture water and sludge mixture could be accomplished by strain SDSWS8. This study may provide a promising candidate strain for sulfide-rich water treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: Tacrolimus-a widely used immunosuppressant to prevent allograft rejection after organ transplantation-is nephrotoxic, increasing the risk of kidney injury accompanied by kidney fibrosis. The mammalian target of rapamycin (mTOR) inhibitor, everolimus, is an immunosuppressant used together with tacrolimus. Although mTOR signaling inhibition has been demonstrated to exhibit antifibrotic effects, the efficacy of everolimus against tacrolimus-induced kidney fibrosis has not been explored. Therefore, we evaluated the protective effects of everolimus against tacrolimus-induced kidney fibrosis., Main Methods: To assess antifibrotic effect of everolimus against tacrolimus-induced kidney fibrosis, male Wistar rats were subcutaneously administered vehicle or tacrolimus (5 mg/kg per day) and/or everolimus (0.2 mg/kg per day) for 2 weeks after bilateral renal ischemia for 45 min. The antifibrotic effect of everolimus was also assessed using rat kidney fibroblast cell line (NRK-49F)., Key Findings: Tacrolimus administration increased predominant profibrotic cytokine transforming growth factor-β (TGF-β) and fibroblast activation marker α-smooth muscle actin (α-SMA) expression and promoted the infiltration of macrophages in the kidney cortex, resulting in renal interstitial fibrosis in rats. Tacrolimus increased serum creatinine, blood urea nitrogen, kidney injury molecule-1 (KIM-1), and kidney injuries, such as tubular dilation, vacuolization, and glomerular atrophy. Everolimus administration attenuated tacrolimus-induced kidney fibrosis and the associated abnormalities. Everolimus strongly suppressed TGF-β-induced kidney fibroblast activation and extracellular matrix protein expression by the mTOR signaling inhibition., Significance: We demonstrated that everolimus attenuates tacrolimus-induced renal interstitial fibrosis in rats. Owing to its protective effect against tacrolimus-induced kidney fibrosis, everolimus may be useful when used concomitantly with tacrolimus., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Seasonal cyanobacterial blooms in eutrophic water releases algal organic matter (AOM), which contains large amount of dissolved organic nitrogen (DON) and is difficult to be removed effectively by conventional treatment processes (e.g., coagulation and sand filtration) because of its high hydrophilicity. Moreover, N-nitrosodimethylamine (NDMA) can be generated by the reaction of AOM with disinfectants in the subsequent disinfection process. In this study, the formation of NDMA from different AOM components was explored and the control of algal-derived NDMA precursors by UV/H 2 O 2 /O 3 was evaluated. The results showed that the hydrophilic and polar components of AOM with the low molecular weight had higher NDMA yields. UV-based advanced oxidation process (AOPs) is effective in degrading NDMA precursors, while the removal rate can be affected greatly by UV doses. The removal rate of NDMA precursors by UV/H 2 O 2 /O 3 is higher than by UV/H 2 O 2 or UV/O 3 which can reach 95% at the UV dose of 400 mJ/cm 2 . An alkaline environment reduces the oxidation efficiency of UV/H 2 O 2 /O 3 technology, while an acidic environment is conducive to its function. Inorganic anions such as HCO 3 - , SO 4 2- , Cl - and NO 3 - are potential to compete with target algal-derived NDMA precursors for the oxidants reaction and inhibit the degradation/removal of these precursors. The degradation of algal-derived NDMA precursors by UV/H 2 O 2 /O 3 is mainly accomplished by the oxidation of DON with secondary amide groups, and the main degradation mechanism by UV/H 2 O 2 /O 3 was through the initial decomposition of macromolecular organic compounds such as biopolymers and humic substances and the further degradation of resulting small molecular components., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled “Using UV/H(2)O(2)/O(3) technology to control N-nitrosodimethylamine precursor release from AOM: formation characteristics, water matrix effects and degradation pathway”., (Copyright © 2021. Published by Elsevier B.V.)

Nephrotoxicity is the major adverse reaction to tacrolimus; however, the underlying mechanisms remain to be fully elucidated. Although several tacrolimus-induced nephrotoxicity animal models have been reported, most renal injury rat models contain factors other than tacrolimus. Here, we report the development of a new nephrotoxicity with interstitial fibrosis rat model induced by tacrolimus administration. Thirty Wistar rats were randomly divided into four groups: sham-operated (Sham), vehicle-treated ischemia reperfusion (I/R) injury (IRI), tacrolimus treated (TAC) and tacrolimus treated I/R injury (TAC + IRI). Rats subjected to IR injury and treated with tacrolimus for 2 weeks showed higher serum creatinine (Scr), blood urea nitrogen (BUN), serum magnesium (Mg) and serum potassium (K), indicating decreased renal function. In addition, tacrolimus treatment combined with IR injury increased histological injury (tubular vacuolation, glomerulosclerosis and interstitial fibrosis), as well as α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), and kidney injury molecule-1 (KIM-1) expression in the renal cortex. In summary, we have developed a tacrolimus-induced kidney injury rat model with interstitial fibrosis within 2 weeks by creating conditions mimicking renal transplantation via tacrolimus administration following ischemia-reperfusion., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Phosphorus (P) and nitrogen (N) pollution are the worldwide challenging problem. In the present study, a new salt-tolerant phosphate-accumulating organism (PAO) was isolated and identified as Bacillus subtilis GHSP10. Strain GHSP10 did not produce hemolysin and showed high susceptibility to antibiotics. The favorable phosphorus removal C/N ratios, P/N ratios, temperature, salinities, pH values and shaking speeds of strain GHSP10 were 10-20, 0.1-0.2, 28 °C, 0-3%, 7.5-8.5 and 100-250 r/min. Besides, strain GHSP10 could conduct heterotrophic nitrification-aerobic denitrification and the maximal removal efficiencies of ammonium, nitrite and nitrate were 99.52%, 81.10% and 95.84% respectively. Moreover, the phosphorus removal process of strain GHSP10 was achieved under entirely aerobic conditions, and glycogen and poly-β-hydroxybutyrate could provide energy source for the phosphorus removal process of strain GHSP10. The amplification of ppk, hao, napA, narG, nirK genes as well as the expression of polyphosphate kinase helped to reveal the removal pathways of phosphorus and nitrogen, providing theoretical support for the phosphorus removal, nitrification and aerobic denitrification abilities of strain GHSP10. Furthermore, efficient removal of phosphorus and nitrogen from both domestic sewage and aquaculture sewage could be accomplished by strain GHSP10. This study may provide a hopeful candidate strain for simultaneous removal of phosphorus and nitrogen pollution from both freshwater sewage and saline sewage., Competing Interests: Declaration of competing interest There were no conflicts of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Previous research found that inhalation exposure of reclaimed water could cause severe pulmonary inflammation, and the endotoxin was proposed to be the key risk factor. To further support this view, the toxic effects of different reclaimed water induced by acute inhalation exposure were compared between wildtype C57BL/6J and TLR4 signaling pathway defect mice. It was found that reclaimed water with high levels of endotoxin could induce strong inflammation in wildtype mice, but not in Tlr4 -/- and MyD88 -/- mutants. The mixed bacterial culture from the reclaimed water showed very weak response in wildtype mice and no response in TLR4-signaling pathway deficient mice, which further suggested that the cell-bound endotoxins contribute little in the inflammation induced by reclaimed water. In addition, conditional knockout of the Tlr4 gene in myeloid cells resulted in a significant reduction of sensitivity to the reclaimed water in mutants, which indicates that myeloid cells play the most important role in the defensive immune system against the pollutants in the water. In general, this study demonstrated that the TLR4-MyD88 signaling pathway is responsible for the acute lung inflammation induced by reclaimed water, which excludes the possibility of other signaling pathway dependent inflammation inducers in reclaimed water., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The rapid expansion of aquaculture industry brings about significant environmental concerns, especially nitrogen pollution. Compared to nitrogen bioconversion implemented by the conventional autotrophic nitrifiers and anaerobic denitrifiers, bacteria capable of heterotrophic nitrification-aerobic denitrification (HNAD) in mariculture environments have yet to be well understood. In this study, twenty-five species of new halophilic HNAD bacteria were isolated and identified from mariculture water. By these strains co-cultured in the synthetic mariculture water (ammonia: 5 mg/L, C/N: 5, salinity: 30‰), microbial dynamic analysis showed that ammonia were mainly removed by dominant genera of Marinomonas, Marinobacterium, Halomonas, and Cobetia which simultaneously had positive correlations to total nitrogen removal. Metagenomic annotations revealed that inorganic-N was converted into gaseous-N and organic-N by these HNAD bacteria through nitrogen metabolism pathways of assimilation, partial nitrification, nitroalkane oxidation, nitrate/nitrite dissimilation reduction, and denitrification. Among them, due to the interspecific coexistence and cooperation, Marinomonas communis &Halomonas titanicae, Marinomonas communis &Cobetia marina, Marinomonas aquimarina &Halomonas titanicae, and Marinomonas aquimarina &Cobetia marina exhibited significantly better inorganic-N removal efficiency and stability. The four novel bacterial consortia could transform approximately 60% of initial ammonia into intracellular organic-N (18-20%) and gaseous-N (36-38%), which were significantly higher than those of their single strains. These findings will contribute to understanding and developing the culturable HNAD bacteria as promising candidates for nitrogen pollution control and water bioremediation in mariculture or other saline environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Absolute quantification of waterborne pathogens is mandatory for microbiological risk assessment (MRA). Determination of the DNA recovery efficiency is an essential step before the quantitative molecular measurements, which has been largely ignored. In this study, we compared the DNA recovery efficiency and quality of five extraction methods, including two modified phenol-chloroform-based extractions with mechanical shearing and three commercial kits for the extraction of DNA from indigenous mixed-bacteria culture of river water. All of the methods gave relatively satisfying results from the pelleted sample through centrifugation. However, the commercial kits provided surprisingly low DNA yields for membrane-filtered samples because of DNA trapping and/or absorption on the membrane. Integrating with enzymatic lysis, bath sonication, phenol extraction, and alcohol precipitation achieved highest DNA yields and an acceptable DNA integrity for quantitative PCR. A plasmid containing the human GADPH gene fragment was demonstrated to be a suitable spiking control for determining the absolute DNA recovery efficiency. The unexpectedly low efficiencies of commercial kit extractions imply the significant underestimation of pathogenic bacteria in previous studies, which should gain enough concern in the area of pathogen monitoring in the future., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Laparoscopic splenectomy (LS) is considered as the gold standard in the surgical management of non-traumatic diseases of spleen (NDOS), and robotic splenectomy (RS) is a promising alternative treatment. This study aimed to compare the effectiveness and safety of RS versus LS for NDOS. Several databases were systematically searched for the literature that compared RS with LS for NDOS. Primary outcomes included operative time, blood loss, conversion to open, hospital stay, cost, postoperative complication, and postoperative morbidity. Study-specific effect sizes and their 95% confidence interval (CI) were combined to calculate the pooled value using a fixed-effects or random-effects model. Seven studies were included with 374 patients. Major blood loss (mean difference [MD] = -127.14; 95% CI = -199.87-54.42), conversion to open (rate difference [RD] = -0.06; 95% CI = -0.11-0.01), and postoperative complication (RD = -0.10; 95% CI = -0.20-0.01) were less in the RS group compared with the LS group. There were no differences found in operative time and hospital stay. In our meta-analysis, perioperative mortality was not observed in the RS group. Compared with the LS group, RS group showed comparable effectiveness and safety for the treatment of NDOS based on the current evidence., (Copyright © 2019. Published by Elsevier Taiwan LLC.)

An investigation to study the distribution and persistence of cephalosporins in the cephalosporin producing wastewater was carried out in this paper. The target cephalosporins included ceftriaxone (CRO), cefalexin (CEF), cefotaxime (CTX), cefazolin (CZO), cefuroxime (CXM), cefoxitin (CFX) and cefradine (CF). A rapid and reliable detection method for cephalosporins was established based on solid phase extraction and ultra-performance liquid chromatography - tandem mass spectrometry. In the cephalosporin producing wastewater effluent (CPWWeff), the limit of quantification for the targets ranged from 27.5ng/L to 131.8ng/L, and the recoveries for all of the analytes ranged from 73% to 102%. The mean concentrations of the seven cephalosporins were 12.85-141.55μg/L and 0.05-24.38μg/L in cephalosporin producing wastewater influent and effluent, respectively. Although high removal efficiencies were achieved for the cephalosporins (78.8-99.7%), up to 1.9kg of cephalosporins was discharged per day from the investigated C-WWTP. The degradation processes of CRO, CEF, CZO and CXM followed first-order kinetics in CPWWeff under all of the testing conditions. The degradation rates of tested cephalosporins were accelerated by high temperature and light. Persistence of CXM was the highest among the four tested cephalosporins in CPWWeff., (Copyright © 2016. Published by Elsevier B.V.)

A mixed micelle that comprised of monomethylol poly(ethylene glycol)-poly(D,L-lactic acid) (MPP), D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and stearic acid grafted chitosan oligosaccharide(CSO-SA) copolymers was developed to enhance the oral absorption of docetaxel (DTX). DTX-loaded MPP/TPGS/CSO-SA mixed polymeric micelles (MPMs) were prepared with thin film hydration method and characterized in terms of morphology, size, zeta potential, encapsulation efficiency, critical micellization concentration, and in vitro stability in media modeling physiological conditions. The in vitro release of docetaxel from the mixed micelles was studied with dialysis method. The oral bioavailability studies were conducted in rats and the pharmacokinetic parameters were evaluated. The results showed that DTX-loaded MPP/TPGS/CSO-SA MPMs had a mean diameter of 34.96 nm and exhibited spherical shape under transmission electron microscopy. The drug loading of DTX in the mixed micelles was 19.15%. The critical micellization concentration of MPP/TPGS/CSO-SA copolymer was 2.11×10(-5) M, and the size of mixed micelles in gastric fluid (pH 1.6) for 2 h and simulated intestinal fluid (pH 6.5) for 6h showed no significant change. The in vitro release study showed that DTX-loaded MPP/TPGS/CSO-SA MPMs exhibited slower release characteristics compared to DTX solution. The oral bioavailability of the DTX-loaded MPP/TPGS/CSO-SA MPMs was increased by 2.52 times compared to that of DTX solution. The current results encourage further development of DTX mixed polymeric micelles as the oral drug delivery system., (Copyright © 2013 Elsevier B.V. All rights reserved.)