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1.
iScience ; 27(6): 109906, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38947530

ABSTRACT

Trichodesmium is one of the dominant dinitrogen (N2) fixers in the ocean, influencing global carbon and nitrogen cycles through biochemical reactions. Although its photosynthetic activity fluctuates rapidly, the physiological or ecological advantage of this fluctuation is unclear. We develop a metabolic model of Trichodesmium that can perform daytime N2 fixation. We examined (1) the effect of the duration of switches between photosynthetic and non-photosynthetic cellular states and (2) the effect of the presence and absence of N2 fixation in photosynthetic states. Results show that a rapid switch between photosynthetic and non-photosynthetic states increases Trichodesmium growth rates by improving metabolic efficiencies due to an improved balance of C and N metabolism. This provides a strategy for previous paradoxical observations that all Trichodesmium cells can contain nitrogenase. This study reveals the importance of fluctuating photosynthetic activity and provides a mechanism for daytime N2 fixation that allows Trichodesmium to fix N2 aerobically in the global ocean.

2.
Biochem Pharmacol ; 226: 116411, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38972428

ABSTRACT

Investigating and identifying pathogenic molecules of non-alcoholic fatty liver disease (NAFLD) has become imperative, which would serve as effective targets in the future. We established high-fat diet (HFD)-induced NAFLD model in mice and palmitic acid (PA)-induced model in mouse AML12 cells. The level of miR-218-5p was examined by qRT-PCR, and Elovl5 was identified as the potential target gene of miR-218-5p. The binding relationship between miR-218-5p and Elovl5 was validated by double luciferase reporter gene assay, and inhibition/overexpression of miR-218-5p in vitro. The functional mechanisms of miR-218-5p/Elovl5 in regulating lipogenesis in NAFLD were investigated in vivo and in vitro through gain- and loss-of-function studies. MiR-218-5p was significantly increased, and Elovl5 was decreased in model group. According to the double luciferase reporter and gene interference experiments in AML12 cells, Elovl5 was a target gene of miR-218-5p and its expression was regulated by miR-218-5p. The SREBP1-mediated lipogenesis signaling pathway regulated by Elovl5 was upregulated in model group. Moreover, silencing of miR-218-5p significantly upregulated Elovl5 expression, and suppressed SREBP1 signaling pathway in PA-induced AML-12 cells. Correspondingly, the cell injury, elevated TC, TG contents and lipid droplet accumulation were ameliorated. Furthermore, the effect of miR-218-5p on lipogenesis in vitro and in vivo was obstructed by si-Elovl5, implicating that miR-218-5p promotes lipogenesis by targeting ELOVL5 in NAFLD. miR-218-5p could promote fatty acid synthesis by targeting Elovl5, thereby accelerating the development of NAFLD, which is one of the key pathogenic mechanisms of NAFLD and provides a new molecular target for the management of NAFLD.

3.
Environ Sci Technol ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38978502

ABSTRACT

The migration and risk of organophosphate esters (OPEs) in agricultural air-soil-plant multimedia systems due to plastic film application remain unclear. This study investigates the multimedia distribution of traditional OPEs (TOPEs), novel OPEs (NOPEs), and their transformation products (POPEs) in plastic and solar greenhouses. The total concentration of OPE-associated contaminants in air and airborne particles ranged from 594 to 1560 pg/m3 and 443 to 15600 ng/g, respectively. Significant correlations between air OPE concentrations and those in polyolefin film (P < 0.01) indicate plastic film as the primary source. Contaminants were also found in soils (96.8-9630 ng/g) and vegetables (197-7540 ng/g). The primary migration pathway for NOPEs was particle dry deposition onto the soil and leaf, followed by plant accumulation. Leaf absorption was the main uptake pathway for TOPEs and POPEs, influenced by vegetable specific leaf surface area. Moreover, total exposure to OPE-associated contaminants via vegetable intake was assessed at 2250 ng/kg bw/day for adults and 2900 ng/kg bw/day for children, with an acceptable hazard index. However, a high ecological risk was identified for NOPE compounds (median risk quotient, 975). This study provides the first evidence of the multimedia distribution and potential threat posed by OPE-associated contaminants in agricultural greenhouses.

4.
Angew Chem Int Ed Engl ; : e202408277, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38979699

ABSTRACT

Since the discovery of the first peroxidase nanozyme (Fe3O4), numerous nanomaterials have been reported to exhibit intrinsic enzyme-like activity toward inorganic oxygen species, such as H2O2, oxygen, and O2•-. However, the exploration of nanozymes targeting organic compounds holds transformative potential in the realm of industrial synthesis. This review provides a comprehensive overview of the diverse types of nanozymes that catalyze reactions involving organic substrates and discusses their catalytic mechanisms, structure-activity relationships, and methodological paradigms for discovering new nanozymes. Additionally, we propose a forward-looking perspective on designing nanozyme formulations to mimic subcellular organelles, such as chloroplasts, termed "nano-organelles". Finally, we analyze the challenges encountered in nanozyme synthesis, characterization, nano-organelle construction and applications while suggesting directions to overcome these obstacles and enhance nanozyme research in the future. Through this review, our goal is to inspire further research efforts and catalyze advancements in the field of nanozymes, fostering new insights and opportunities in chemical synthesis.

5.
Nat Commun ; 15(1): 5678, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38971858

ABSTRACT

Inherited non-hemolytic anemia is a group of rare bone marrow disorders characterized by erythroid defects. Although concerted efforts have been made to explore the underlying pathogenetic mechanisms of these diseases, the understanding of the causative mutations are still incomplete. Here we identify in a diseased pedigree that a gain-of-function mutation in toll-like receptor 8 (TLR8) is implicated in inherited non-hemolytic anemia. TLR8 is expressed in erythroid lineage and erythropoiesis is impaired by TLR8 activation whereas enhanced by TLR8 inhibition from erythroid progenitor stage. Mechanistically, TLR8 activation blocks annexin A2 (ANXA2)-mediated plasma membrane localization of STAT5 and disrupts EPO signaling in HuDEP2 cells. TLR8 inhibition improves erythropoiesis in RPS19+/- HuDEP2 cells and CD34+ cells from healthy donors and inherited non-hemolytic anemic patients. Collectively, we identify a gene implicated in inherited anemia and a previously undescribed role for TLR8 in erythropoiesis, which could potentially be explored for therapeutic benefit in inherited anemia.


Subject(s)
Anemia , Erythropoiesis , Toll-Like Receptor 8 , Humans , Erythropoiesis/genetics , Toll-Like Receptor 8/metabolism , Toll-Like Receptor 8/genetics , Female , Anemia/genetics , Male , Pedigree , Erythropoietin/metabolism , Erythropoietin/genetics , Adult , Signal Transduction , Mutation , Erythroid Cells/metabolism , Animals , Erythroid Precursor Cells/metabolism
6.
Thromb Haemost ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38959956

ABSTRACT

BACKGROUND: Sepsis-induced coagulopathy (SIC) is a common cause of poor prognosis in critically ill patients in the intensive care unit (ICU). This study aimed to develop a predictive nomogram incorporating clinical markers and scoring systems to individually predict the probability of SIC in septic patients. METHODS: Patients consecutively recruited in the stage between January 2022 and April 2023 constituted the development cohort for retrospective analysis to internally test the nomogram, and patients in the stage between May 2023 to November 2023 constituted the validation cohort for prospective analysis to external validate the nomogram. The nomogram was validated in an independent external validation cohort, involving discrimination and calibration. A decision curve analysis was also performed to evaluate the net benefit of the insertion decision with this nomogram. RESULTS: A total of 548 and 245 patients were included in the development and validation cohort, respectively. Predictors contained in the prediction nomogram included shock, platelets and INR. Patients with shock (OR, 4.499; 95% CI, 2.730-7.414; P < 0.001) , higher INR (OR, 349.384; 95% CI, 62.337-1958.221; P < 0.001) and lower platelet (OR, 0.985; 95% CI, 0.982-0.988; P < 0.001) had higher probabilities of SIC. The development model showed good discrimination, with an AUROC of 0.879(95%CI, 0.850-0.908)and good calibration. Application of the nomogram in the validation cohort also gave good discrimination with an AUROC of 0.872(95%CI,0.826-0.917)and good calibration. CONCLUSIONS: By incorporating shock, platelets and INR in the model, this useful nomogram could be accessibly utilized to predict SIC occurrence in septic patients.

7.
Environ Res ; : 119553, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38964573

ABSTRACT

Evidence regarding the link between long-term ambient ozone (O3) exposure and childhood sleep disorders is little. This study aims to examine the associations between long-term exposure to O3 and sleep disorders in children. We conducted a population-based cross-sectional survey, including 185,428 children aged 6 to 18 years in 173 schools across 14 Chinese cities during 2012 and 2018. Parents or guardians completed a checklist using Sleep Disturbance Scale for Children, and O3 exposure at residential and school addresses was estimated using a satellite-based spatiotemporal model. We used generalized linear mixed models to test the associations with adjustment for factors including socio-demographic variables, lifestyle, meteorology and multiple pollutants. Mean concentrations of O3, particulate matter with diameters ≤2.5 mm (PM2.5) and nitrogen dioxide (NO2) were 88.9 µg/m3, 42.5 µg/m3 and 34.4 µg/m3, respectively. O3 and NO2 concentrations were similar among provinces, while PM2.5 concentration varied significantly among provinces. Overall, 19.4% of children had at least one sleep disorder. Long-term exposure to O3 was positively associated with odds of sleep disorders for all subtypes. For example, each interquartile increment in home-school O3 concentrations was associated with a higher odds ratio for global sleep disorder, at 1.22 (95% confidence interval: 1.18, 1.26). Similar associations were observed for sleep disorder subtypes. The associations remained similar after adjustment for PM2.5 and NO2. Moreover, these associations were heterogeneous regionally, with more prominent associations among children residing in southeast region than in northeast and northwest regions in China. We concluded that long-term exposure to O3 is positively associated with risks of childhood sleep disorders. These associations varied by geographical region of China.

8.
Int J Biol Macromol ; 275(Pt 1): 133578, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38960272

ABSTRACT

Tannic acid (TA) is a natural polyphenol that shows great potential in the field of biomedicine due to its anti-inflammatory, anti-oxidant, anti-bacterial, anti-tumor, anti-virus, and neuroprotective activities. Recent studies have revealed that liquid-liquid phase separation (LLPS) is closely associated with protein aggregation. Therefore, modulating LLPS offers new insights into the treatment of neurodegenerative diseases. In this study, we investigated the influence of TA on the LLPS of the Alzheimer's-related protein tau and the underlying mechanism. Our findings indicate that TA affects the LLPS of tau in a biphasic manner, with initial promotion and subsequent suppression as the TA to tau molar ratio increases. TA modulates tau phase separation through a combination of hydrophobic interactions and hydrogen bonds. The balance between TA-tau and tau-tau interactions is found to be relevant to the material properties of TA-induced tau condensates. We further illustrate that the modulatory activity of TA in phase separation is highly dependent on the target proteins. These findings enhance our understanding of the forces driving tau LLPS under different conditions, and may facilitate the identification and optimization of compounds that can rationally modulate protein phase transition in the future.

9.
PLoS One ; 19(7): e0306694, 2024.
Article in English | MEDLINE | ID: mdl-38980844

ABSTRACT

Serial correlations within temperature time series serve as indicators of the temporal consistency of climate events. This study delves into the serial correlations embedded in global surface air temperature (SAT) data. Initially, we preprocess the SAT time series to eradicate seasonal patterns and linear trends, resulting in the SAT anomaly time series, which encapsulates the inherent variability of Earth's climate system. Employing diverse statistical techniques, we identify three distinct types of serial correlations: short-term, long-term, and nonlinear. To identify short-term correlations, we utilize the first-order autoregressive model, AR(1), revealing a global pattern that can be partially attributed to atmospheric Rossby waves in extratropical regions and the Eastern Pacific warm pool. For long-term correlations, we adopt the standard detrended fluctuation analysis, finding that the global pattern aligns with long-term climate variability, such as the El Niño-Southern Oscillation (ENSO) over the Eastern Pacific. Furthermore, we apply the horizontal visibility graph (HVG) algorithm to transform the SAT anomaly time series into complex networks. The topological parameters of these networks aptly capture the long-term correlations present in the data. Additionally, we introduce a novel topological parameter, Δσ, to detect nonlinear correlations. The statistical significance of this parameter is rigorously tested using the Monte Carlo method, simulating fractional Brownian motion and fractional Gaussian noise processes with a predefined DFA exponent to estimate confidence intervals. In conclusion, serial correlations are universal in global SAT time series and the presence of these serial correlations should be considered carefully in climate sciences.


Subject(s)
Temperature , Algorithms , Climate , Time Factors , Seasons , El Nino-Southern Oscillation
10.
Environ Sci Technol ; 58(24): 10524-10535, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38832650

ABSTRACT

In the context of escalating urban heat events due to climate change, air conditioning (AC) has become a critical factor in maintaining indoor thermal comfort. Yet the usage of AC can also exacerbate outdoor heat stress and burden the electricity system, and there is little scientific knowledge regarding how to balance these conflicting goals. To address this issue, we established a coupled modeling approach, integrating the Weather Research and Forecasting model with the building energy model (WRF_BEP + BEM), and designed multiple AC usage scenarios. We selected Chongqing, China's fourth-largest megacity, as our study area due to its significant socioeconomic importance, the severity of extreme heat events, and the uniqueness of its energy infrastructure. Our analysis reveals that AC systems can substantially reduce indoor temperatures by up to 18 °C; however, it also identifies substantial nighttime warming (2-2.5 °C) and a decline in thermal comfort. Particularly for high-density neighborhoods, when we increase 2 °C indoors, the outdoor temperature can be alleviated by up to 1 °C. Besides, despite the limited capacity to regulate peak electricity demand, we identified that reducing the spatial cooled fraction, increasing targeted indoor temperature by 2 °C, and implementing temporal AC schedules can effectively lower energy consumption in high-density neighborhoods, especially the reduction of spatial cooled fraction (up to 50%). Considering the substantial demand for cooling energy, it is imperative to carefully assess the adequacy and continuity of backup energy sources. The study underscores the urgency of reassessing energy resilience and advocates for addressing the thermal equity between indoor and outdoor environments, contributing to the development of a sustainable and just urban climate strategy in an era of intensifying heat events.


Subject(s)
Air Conditioning , Climate Change , China , Temperature , Models, Theoretical
11.
J Affect Disord ; 361: 556-563, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38925314

ABSTRACT

OBJECTIVE: To investigate the effect of 20/4Hz transcutaneous auricular vagus nerve stimulation (taVNS) on anxiety symptoms in Parkinson's disease (PD) and the potential neural mechanism. METHODS: In the current randomized, double-blind, sham-controlled trial, 30 PD patients with anxiety (PD-A), 30 PD patients without anxiety (PD-nA), and 30 healthy controls (HCs) were enrolled. PD-A patients were randomly (1:1) allotted to real taVNS stimulation group (RS) or sham stimulation group (SS) to explore the efficacy of a two-week treatment of taVNS to promote anxiety recovery. Simultaneously, all participants were measured activation in the bilateral prefrontal cortex during verbal fluency task (VFT) using functional near-infrared spectroscopy. RESULTS: PD-A patients showed significantly decreased oxyhemoglobin in the left triangle part of the inferior frontal gyrus (IFG) during VFT, which was negatively related to the severity of anxiety symptoms. After two-week treatment of taVNS, the interaction of group and time had significant effect on HAMA scores (F = 18.476, p < 0.001, η2 = 0.398). In RS group, compared with baseline, HAMA scores decreased significantly in the post-treatment and follow-up condition (both p < 0.001). Meanwhile, in RS group, HAMA scores were lower than those in SS group in the post-treatment and follow-up condition (p = 0.006, <0.001, respectively). Furthermore, the 20/4Hz taVNS remarkably ameliorated anxiety symptoms in PD patients, directly correlated with the increased activation of the left triangle part of the IFG during VFT in RS group. CONCLUSION: Our results depicted that taVNS could ameliorate the anxiety symptoms of PD-A patients and regulated the function of the left triangle part of the IFG.

12.
IET Nanobiotechnol ; 2024: 9970665, 2024.
Article in English | MEDLINE | ID: mdl-38863971

ABSTRACT

Pancreatic cancer is a leading cause of cancer-related deaths worldwide. Conventional therapies often provide limited success, necessitating the need for novel therapeutic strategies. Oncolytic viruses (OVs) are a class of viruses that specifically target and kill cancer cells while leaving normal cells unharmed. These viruses have shown promise in the treatment of various cancers, including pancreatic cancer. However, their use in clinical settings has been limited by several factors. Their inability to efficiently infect and kill tumor cells. To overcome this limitation, a cell membrane-coated oncolytic virus was developed. However, the necessity of homologous and nonhomologous tumor cell membranes for their function has not yet been proven. This novel virus displayed increased infectivity and killing activity against tumor cells compared to nonhomologous tumor cell membranes and noncoated viruses. We believe that the homologous tumor cell membranes-coated OVs can enhance the therapeutic potential for pancreatic cancer therapy.


Subject(s)
Cell Membrane , Oncolytic Virotherapy , Oncolytic Viruses , Pancreatic Neoplasms , Pancreatic Neoplasms/therapy , Pancreatic Neoplasms/pathology , Humans , Oncolytic Virotherapy/methods , Oncolytic Viruses/physiology , Cell Line, Tumor , Animals
13.
Int Urol Nephrol ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38842659

ABSTRACT

OBJECTIVE: To investigate the association between serum 25(OH)D and kidney stone disease (KSD) in participants from the UK Biobank. METHODS: We used data from the UK Biobank. Our analysis involved Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to estimate the association between serum 25(OH)D levels (measured at the time of recruitment) and the risk of KSD, which was determined using hospital records. RESULTS: This study involved 444,343 participants, with 4,458 cases of KSD identified during an average follow-up period of 12.6 years. Higher 25(OH)D levels were not associated with developing kidney stones in general population model 3 (HR = 0.88 [95% CI 0.77-1.01]). Interestingly, higher serum 25(OH)D concentrations in women over 60 years old were associated with a lower risk of kidney stone disease. The multivariate HRs and 95% CIs for participants who had serum 25(OH)D ≥ 50 nmol/L or ≥ 75 nmol/L, compared with those who were severely deficient (25[OH]D < 25 nmol/L), were 0.74 (0.58-0.95), 0.60 (0.43-0.85) for KSD, respectively (P for trend < 0.01). However, this trend was not statistically significant in the subgroup analysis of serum calcium ion concentration. CONCLUSION: High 25(OH)D levels were not associated with a higher incidence of kidney stones if serum calcium levels are within a normal range. The findings alleviate physiological concerns regarding the supplementation of vitamin D alone to raise serum 25(OH)D concentration.

14.
Oncogenesis ; 13(1): 21, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38871685

ABSTRACT

The hypercoagulable state is a hallmark for patients with multiple myeloma (MM) and is associated with disease progression. Activated platelets secrete exosomes and promote solid tumor growth. However, the role of platelet-derived exosomes in MM is not fully clear. We aim to study the underlying mechanism of how platelet-derived exosomes promote MM cell growth. Flow cytometry, Western blot, proteome analysis, co-immunoprecipitation, immunofluorescence staining, and NOD/SCID mouse subcutaneous transplantation model were performed to investigate the role of exosomal LRG1 on multiple myeloma cell growth. Peripheral blood platelets in MM patients were in a highly activated state, and platelet-rich plasma from MM patients significantly promoted cell proliferation and decreased apoptotic cells in U266 and RPMI8226 cells. Leucine-rich-alpha-2-glycoprotein 1 (LRG1) was significantly enriched in MM platelet-derived exosomes. Blocking LRG1 in recipient cells using LRG1 antibody could significantly eliminate the proliferation-promoting effect of platelet-derived exosomes on MM cells. And high exosomal LRG1 was associated with poor prognosis of patients with MM. Mechanistic studies revealed that LRG1 interacted with Olfactomedin 4 (OLFM4) to accelerate MM progression by activating the epithelial-to-mesenchymal transition (EMT) signaling pathway and promoting angiogenesis. Our results revealed that blocking LRG1 is a promising therapeutic strategy for the treatment of MM.

15.
J Invest Dermatol ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38823435

ABSTRACT

TRPV3 is a temperature-sensitive calcium-permeable channel. In previous studies, we noticed prominent TUNEL-positive keratinocytes in patients with Olmsted syndrome and Trpv3+/G568V mice, both of which carry gain-of-function variants in the TRPV3 gene. However, it remains unclear how the keratinocytes die and whether this process contributes to more skin disorders. In this study, we showed that gain-of-function variant or pharmacological activation of TRPV3 resulted in poly(ADP-ribose) polymerase 1 (PARP1)/AIFM1/macrophage migration inhibitory factor axis-mediated parthanatos, which is an underestimated form of cell death in skin diseases. Chelating calcium, scavenging ROS, or inhibiting nitric oxide synthase effectively rescued the parthanatos, indicating that TRPV3 regulates parthanatos through calcium-mediated oxidative stress. Furthermore, inhibiting PARP1 downregulated TSLP and IL33 induced by TRPV3 activation in HaCaT cells, reduced immune cell infiltration, and ameliorated epidermal thickening in Trpv3+/G568V mice. Marked parthanatos was also detected in the skin of MC903-treated mice and patients with atopic dermatitis, whereas inhibiting PARP1 largely alleviated the MC903-induced dermatitis. In addition, stimulating parthanatos in mouse skin with methylnitronitrosoguanidine recapitulated many features of atopic dermatitis. These data demonstrate that the TRPV3-regulated parthanatos-associated PARP1/AIFM1/macrophage migration inhibitory factor axis is a critical contributor to the pathogenesis of Olmsted syndrome and atopic dermatitis, suggesting that modulating the PARP1/AIFM1/macrophage migration inhibitory factor axis is a promising therapy for these conditions.

16.
Article in English | MEDLINE | ID: mdl-38701346

ABSTRACT

OBJECTIVE: While some studies have suggested an association between metabolic syndrome and kidney stones, the quality and level of evidence in these studies vary. Whether some individual characteristics and clustering of metabolic syndrome traits increase the risk of kidney stones has not been examined in a large-scale prospective cohort. MATERIALS: We conducted a retrospective analysis of data from a prospective cohort of 487,860 UK Biobank participants who were free from kidney stones at baseline. The presence of metabolic syndrome was based on five criteria: abdominal obesity, high triglyceride levels, low high-density lipoprotein (HDL) cholesterol levels, high blood pressure (HBP), and type 2 diabetes mellitus (T2DM). Cox proportional hazards regression models were used to evaluate the association between metabolic syndrome and risk of kidney stones. RESULTS: After an average follow-up period of 12.6 years, a total of 5,213 of the 487,860 participants included in the UK Biobank study developed kidney stones. The partial traits of metabolic syndrome, including waist circumference (HR: 1.15, 95% CI: 1.10-1.20), HDL cholesterol (0.66, 0.55-0.79), HBP (1.11, 1.03-1.19) and T2DM (1.14, 1.04-1.21), were independently associated with the occurrence of kidney stones. The clustering of metabolic syndrome is significantly associated with kidney stone formation, and as the number of metabolic syndrome traits increases, the risk of kidney stones gradually increases. CONCLUSION: Metabolic syndrome is a significant and independent risk factor for the development of kidney stones. This association suggests that kidney stones may represent a systemic disorder influenced by the interplay of various metabolic risk factors.

17.
Sci Rep ; 14(1): 10173, 2024 05 03.
Article in English | MEDLINE | ID: mdl-38702351

ABSTRACT

This study aimed to explore the changes of pharmacokinetic parameters after meropenem in patients with abdominal septic shock after gastrointestinal perforation, and to simulate the probability of different dosing regimens achieving different pharmacodynamic goals. The study included 12 patients, and utilized high performance liquid chromatography-tandem mass spectrometry to monitor the plasma concentration of meropenem. The probability of target attainment (PTA) for different minimum inhibitory concentration (MIC) values and %fT > 4MIC was compared among simulated dosing regimens. The results showed that in 96 blood samples from 12 patients, the clearance (CL) of meropenem in the normal and abnormal creatinine clearance subgroups were 7.7 ± 1.8 and 4.4 ± 1.1 L/h, respectively, and the apparent volume of distribution (Vd) was 22.6 ± 5.1 and 17.2 ± 5.8 L, respectively. 2. Regardless of the subgroup, 0.5 g/q6h infusion over 6 h regimen achieved a PTA > 90% when MIC ≤ 0.5 mg/L. 1.0 g/q6h infusion regimen compared with other regimen, in most cases, the probability of making PTA > 90% is higher. For patients at low MIC, 0.5 g/q6h infusion over 6 h may be preferable. For patients at high MIC, a dose regimen of 1.0 g/q6 h infusion over 6 h may be preferable. Further research is needed to confirm this exploratory result.


Subject(s)
Anti-Bacterial Agents , Meropenem , Microbial Sensitivity Tests , Shock, Septic , Humans , Meropenem/pharmacokinetics , Meropenem/administration & dosage , Meropenem/therapeutic use , Shock, Septic/drug therapy , Male , Female , Middle Aged , Aged , Prospective Studies , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Adult , Intestinal Perforation , Aged, 80 and over
18.
Small ; : e2401100, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38721947

ABSTRACT

The increasing need for energy storage devices with high energy density has led to significant interest in Li-metal batteries (LMBs). However, the use of commercial electrolytes in LMBs is problematic due to their flammability, inadequate performance at low temperatures, and tendency to promote the growth of lithium dendrites and other flaws. This study introduces a localized high-concentration electrolyte (LHCE) that addresses these issues by employing non-flammable electrolyte components and incorporating carefully designed additives to enhance flame retardancy and low-temperature performance. By incorporating additives to optimize the electrolyte, it is possible to attain inorganic-dominated solid electrolyte interphases on both the cathode and anode. This achievement results in a uniform deposition of lithium, as well as the suppression of electrolyte decomposition and cathode deterioration. Consequently, this LHCE achieve over 300 stable cycles for both LiNi0.9Mn0.05Co0.05O2||Li cells and LiCoO2||Li cells, as well as 50 cycles for LiNi0.8Mn0.1Co0.1O2 (NCM811||Li) pouch cells. Furthermore, NCM811||Li cells maintain 84% discharge capacity at -20 °C, in comparison to the capacity at room temperature. The utilization of this electrolyte presents novel perspectives for the safe implementation of LMBs.

19.
Environ Sci Technol ; 58(24): 10740-10751, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38771797

ABSTRACT

The contamination status of novel organophosphate esters (NOPEs) and their precursors organophosphite antioxidants (OPAs) and hydroxylated/diester transformation products (OH-OPEs/di-OPEs) in soils across a large-scale area in China were investigated. The total concentrations of the three test NOPEs in soil were 82.4-716 ng g-1, which were considerably higher than those of traditional OPEs (4.50-430 ng g-1), OPAs (n.d.-30.8 ng g-1), OH-OPEs (n.d.-0.49 ng g-1), and di-OPEs (0.57-21.1 ng g-1). One NOPE compound, i.e., tris(2,4-di-tert-butylphenyl) phosphate (AO168 = O) contributed over 65% of the concentrations of the studied OPE-associated contaminants. A 30-day soil incubation experiment was performed to confirm the influence of AO168 = O on soil bacterial communities. Specific genera belonging to Proteobacteria, such as Lysobacter and Ensifer, were enriched in AO168 = O-contaminated soils. Moreover, the ecological function of methylotrophy was observed to be significantly enhanced (t-test, p < 0.01) in soil treated with AO168 = O, while nitrogen fixation was significantly inhibited (t-test, p < 0.01). These findings comprehensively revealed the contamination status of OPE-associated contaminants in the soil environment and provided the first evidence of the effects of NOPEs on soil microbial communities.


Subject(s)
Antioxidants , Esters , Organophosphates , Soil Microbiology , Soil Pollutants , Soil , Soil/chemistry , Bacteria , China
20.
Redox Biol ; 73: 103175, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38795544

ABSTRACT

Exploring and discovering novel circRNAs is one of the ways to develop innovative drugs for the diagnosis and treatment of myocardial ischemia-reperfusion injury (MI/RI). In the work, some dysregulated circRNAs were found by microarray screening analysis in AC16 cells, and hsa_circRNA_104852 named circMIRIAF was screened, which was up-regulated in AC16 cells damaged by hypoxia-reoxygenation injury (H/RI). The comprehensive analysis of ceRNA network revealed the potential relationship of circMIRIAF/miR-544/WDR12. Then, the results of interaction research confirmed that circMIRIAF acted as sponge of miR-544 to positively regulate WDR12 protein expression. Further, the validation results indicate that miR-544 silencing increased the expression of WDR12, and WDR12 activated Notch1 signal to aggravate H/RI of AC16 cells and MI/RI of mice via regulating oxidative stress and inflammation. Furthermore, silencing circMIRIAF caused the decreased circMIRIAF levels and the increased miR-544 levels in cardiomyocytes, while excessive miR-544 inhibited WDR12 expression to alleviate the disorder. On the contrary, excessive circMIRIAF increased WDR12 expression by adsorbing miR-544 to exacerbate H/RI in AC16 cells. In addition, circMIRIAF siRNA reversed the aggravation of H/RI in cells caused by WDR12 overexpression. Overall, circMIRIAF can serve as a drug target or treating MI/RI, and circMIRIAF could sponge miR-544 and enhance WDR12 expression to aggravate MI/RI, which may provide a novel therapeutic strategy for MI/RI treatment.


Subject(s)
MicroRNAs , Myocardial Reperfusion Injury , RNA, Circular , Animals , Humans , Male , Mice , Cell Line , Disease Models, Animal , Gene Expression Regulation , MicroRNAs/genetics , Myocardial Reperfusion Injury/genetics , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Oxidative Stress , RNA, Circular/genetics , Signal Transduction
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