Metastable precipitation and ion-extractant transport in liquid-liquid separations of trivalent elements.

The extractant-assisted transport of metal ions from aqueous to organic environments by liquid-liquid extraction has been widely used to separate and recover critical elements on an industrial scale. While current efforts focus on designing better extractants and optimizing process conditions, the mechanism that underlies ionic transport remains poorly understood. Here, we report a nonequilibrium process in the bulk aqueous phase that influences interfacial ion transport: the formation of metastable ion-extractant precipitates away from the liquid-liquid interface, separated from it by a depletion region without precipitates. Although the precipitate is soluble in the organic phase, the depletion region separates the two and ions are sequestered in a long-lived metastable state. Since precipitation removes extractants from the aqueous phase, even extractants that are sparingly soluble in water will continue to be withdrawn from the organic phase to feed the aqueous precipitation process. Solute concentrations in both phases and the aqueous pH influence the temporal evolution of the process and ionic partitioning between the precipitate and organic phase. Aqueous ion-extractant precipitation during liquid-liquid extraction provides a reaction path that can influence the extraction kinetics, which plays an important role in designing advanced processes to separate rare earths and other minerals.

Microglial Reactivity Correlates with Presynaptic Loss Independent of ß-Amyloid and Tau.

OBJECTIVE: Triggering receptor expressed on myeloid cells-2 (TREM2) and progranulin (PGRN) are critical regulators of microglia activation and can be detected in cerebrospinal fluid (CSF). However, whether microglial reactivity is detrimental or neuroprotective for Alzheimer disease (AD) is still debatable. METHODS: We identified 663 participants with baseline ß-amyloid (Aß) positron emission tomography (PET) and CSF biomarker data, including phosphorylated tau181 (p-Tau181), soluble TREM2 (sTREM2), PGRN, and growth-associated protein-43 (GAP-43). Among them, 254 participants had concurrent longitudinal CSF biomarkers. We used multivariate regression analysis to study the associations of CSF microglial biomarkers with Aß PET, CSF p-Tau181, and CSF GAP-43 cross-sectionally and longitudinally. A Chinese aging cohort's independent CSF samples (n = 65) were analyzed as a validation. RESULTS: Higher baseline levels of CSF microglial biomarkers were related to faster rates of CSF sTREM2 increase and CSF PGRN decrease. Elevated CSF p-Tau181 was associated with higher levels of CSF microglial biomarkers and faster rates of CSF sTREM2 increase and CSF PGRN decrease. In both cohorts, higher Aß burden was associated with attenuated CSF p-Tau181 effects on CSF microglial biomarker increases. Independent of Aß PET and CSF p-Tau181 pathologies, higher levels of CSF sTREM2 but not CSF PGRN were related to elevated CSF GAP-43 levels and faster rates of CSF GAP-43 increase. INTERPRETATION: These findings suggest that higher Aß burden may attenuate the p-Tau-associated microglial responses, and TREM2-related microglial reactivity may independently correlate with GAP-43-related presynaptic loss. This study highlights the two-edged role of microglial reactivity in AD and other neurodegenerative diseases. ANN NEUROL 2024;95:917-928.

[18F]-D3FSP ß-amyloid PET imaging in older adults and alzheimer's disease.

PURPOSE: [18F]-D3FSP is a new ß-amyloid (Aß) PET imaging tracer designed to decrease nonspecific signals in the brain by reducing the formation of the N-demethylated product. However, its optimal reference region for calculating the standardized uptake value ratio (SUVR) and its relation to the well-established biomarkers of Alzheimer's disease (AD) are still unclear. METHODS: We recruited 203 participants from the Greater Bay Area Healthy Aging Brain Study (GHABS) to undergo [18F]-D3FSP Aß PET imaging. We analyzed plasma Aß42/Aß40, p-Tau181, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) using the Simoa platform. We compared the standardized uptake value (SUV) of five reference regions (cerebellum, cerebellum cortex, brainstem/PONs, white matter, composite of the four regions above) and AD typical cortical region (COMPOSITE) SUVR among different clinical groups. The association of D3FSP SUVR with plasma biomarkers, imaging biomarkers, and cognition was also investigated. RESULTS: Brainstem/PONs SUV showed the lowest fluctuation across diagnostic groups, and COMPOSITE D3FSP SUVR had an enormous effect distinguishing cognitively impaired (CI) individuals from cognitively unimpaired (CU) individuals. COMPOSITE SUVR (Referred to brainstem/PONs) was positively correlated with p-Tau181 (p < 0.001), GFAP (p < 0.001), NfL (p = 0.014) in plasma and temporal-metaROI tau deposition (p < 0.001), and negatively related to plasma Aß42/Aß40 (p < 0.001), temporal-metaROI cortical thickness (p < 0.01), residual hippocampal volume (p < 0.001) and cognition (p < 0.001). The voxel-wise analysis replicated these findings. CONCLUSION: This study suggests brainstem/PONs as an optimal reference region for calculating D3FSP SUVR to quantify cortical Aß plaques in the brain. [18F]-D3FSP could distinguish CI from CU and strongly correlates with well-established plasma biomarkers, tau PET, neurodegeneration, and cognitive decline. However, future head-to-head comparisons of [18F]-D3FSP PET images with other validated Aß PET tracers or postmortem results are crucial.

Visible Light-Regulated Ring-Opening Polymerization of Lactones by Employing Indigo as a Photoacid Catalyst.

The development of visible light-regulated polymerizations for precision synthesis of polymers has drawn considerable attention in the past years. In this study, an ancient dye, indigo, is successfully identified as a new and efficient photoacid catalyst, which can readily promote the ring-opening polymerization of lactones under visible light irradiation in a well-controlled manner, affording the desired polyester products with predictable molecular weights and narrow dispersity. The enhanced acidity of indigos by excitation is crucial to the H-bonding activation of the lactone monomers. Chain extension and block copolymer synthesis are also demonstrated with this method.

Effect of apheresis plasma donation on plasma uric acid levels, the lipid profile, and major plasma proteins in plasma donors in China: A multicenter, prospective cohort study.

Abnormal plasma uric acid (UA) levels, the lipid profile, and plasma proteins in blood are associated with a range of adverse health outcomes. This multicenter, prospective cohort study aimed to determine the possible effects of multiple apheresis plasma donations on plasma UA levels, the lipid profile, and major proteins in plasma donors. Participants were enrolled from 1 April 2021 to 31 August 2022. When their plasma UA (men: >420 µmol/L, women: >360 µmol/L) and/or lipid levels (total cholesterol [TC]: ≥6.2 mmol/L, triglycerides [TGs]: ≥2.3 mmol/L, low-density lipoprotein cholesterol: ≥4.1 mmol/L, or high-density lipoprotein cholesterol [HDL-C]: <1.0 mmol/L) were abnormal at their first plasma donation, the enrolled participants were followed up until they had completed 10 plasma donations. A total of 11485 participants were enrolled, of whom 1861 met the inclusion criteria. During the study period, 320 donors completed 10 plasma donations. None of the participants took any corrective medicine for their abnormal index. The measured parameters were significantly different from the first to the tenth plasma donations (donors with asymptomatic hyperuricemia: UA, P < 0.001; donors with asymptomatic hyperlipidemia: HDL-C, P < 0.001; TC, P = 0.025; TGs, P < 0.001; apolipoprotein B, P = 0.025; all of the plasma donors, immunoglobulin G, P < 0.001). The levels of HDL-C, TC, and apolipoprotein B were increased, and the levels of UA, TGs, and immunoglobulin G were decreased over this time. However, immunoglobulin G levels were still in the normal range. Moreover, the changes in these parameters were closely associated with the frequency of plasma donation during the study period. Repeated apheresis plasma donations can reduce plasma UA and TG levels and increase HDL-C levels; and further evaluation of the clinical significance with a larger sample size is required.

A hybrid proper orthogonal decomposition and next generation reservoir computing approach for high-dimensional chaotic prediction: Application to flow-induced vibration of tube bundles.

Chaotic time series prediction is a central science problem in diverse areas, ranging from engineering, economy to nature. Classical chaotic prediction techniques are limited to short-term prediction of low- or moderate-dimensional systems. Chaotic prediction of high-dimensional engineering problems is notoriously challenging. Here, we report a hybrid approach by combining proper orthogonal decomposition (POD) with the recently developed next generation reservoir computing (NGRC) for the chaotic forecasting of high-dimensional systems. The hybrid approach integrates the synergistic features of the POD for model reduction and the high efficiency of NGRC for temporal data analysis, resulting in a new paradigm on data-driven chaotic prediction. We perform the first chaotic prediction of the nonlinear flow-induced vibration (FIV) of loosely supported tube bundles in crossflow. Reducing the FIV of a continuous beam into a 3-degree-of-freedom system using POD modes and training the three time coefficients via a NGRC network with three layers, the hybrid approach can predict time series of a weakly chaotic system with root mean square prediction error less than 1% to 19.3 Lyapunov time, while a three Lyapunov time prediction is still achieved for a highly chaotic system. A comparative study demonstrates that the POD-NGRC outperforms the other existing methods in terms of either predictability or efficiency. The efforts open a new avenue for the chaotic prediction of high-dimensional nonlinear dynamic systems.

Branched Aluminum Nanocrystals with Internal Hot Spots: Synthesis and Single-Particle Surface-Enhanced Raman Scattering.

Owing to their unique and sustainable surface plasmonic properties, Al nanocrystals have attracted increasing attention for plasmonic-enhanced applications, including single-particle surface-enhanced Raman scattering (SERS). However, whether Al nanocrystals can achieve single-particle SERS is still unknown, mainly due to the synthetic difficulty of Al nanocrystals with internal gaps. Herein, we report a regrowth method for the synthesis of Al nanohexapods with tunable and uniform internal gaps for single-particle SERS with an enhancement factor of up to 1.79 × 108. The uniform branches of the Al nanohexapods can be systematically tuned regarding their dimensions, terminated facets, and internal gaps. The Al nanohexapods generate hot spots concentrated in the internal gaps due to the strong plasmonic coupling between the branches. A single-particle SERS measurement of Al nanohexapods shows strong Raman signals with maximum enhancement factors comparable to that of Au counterparts. The large enhancement factor indicates that Al nanohexapods are good candidates for single-particle SERS.

The Development of Visible-Light Organic Photocatalysts for Atom Transfer Radical Polymerization via Conjugation Extension.

This work aimed to develop organic photocatalysts (PCs) that could mediate organocatalytic atom transfer radical polymerization (O-ATRP) under visible light. Through the core-modification of known chromophoric structures and ring-locking to reach a conjugation extension, annulated N-aryl benzo[kl]acridines were identified as effective visible light-responsive photocatalysts. The corresponding selenium-doped structure showed excellent performance in the O-ATRP of methacrylates, which could afford polymer products with controlled molecular weights and low dispersities under the irradiation of visible light at a 100 ppm catalyst loading.

Efficacy of IVIG therapy for patients with sepsis: a systematic review and meta-analysis.

BACKGROUND: Sepsis is an overwhelming reaction to infection that comes with high morbidity and mortality. It requires urgent interventions in order to improve outcomes. Intravenous immunoglobulins (IVIG) are considered as potential therapy in sepsis patients. Results of trials on IVIG as adjunctive therapy for sepsis have been conflicting due to the variability in population characteristics, country geography and drug dosage form in different studies. METHODS: A systematic article search was performed for eligible studies published up to January, 31, 2023, through the PubMed, Embase, Cochrane Library and Chinese National Knowledge Infrastructure database. The included articles were screened by using rigorous inclusion and exclusion criteria. Subgroup analyses were conducted according to different IVIG types, ages and economic regions. All analyses were conducted using Review Manager 5.4. Quality of studies and risk of bias were evaluated. RESULTS: In total, 31 randomized controlled trials were included with a sample size of 6,276 participants. IVIG could reduce the mortality (RR 0.86, 95% CI: 0.77-0.95, p = 0.005), the hospital stay (MD - 4.46, 95% CI: - 6.35 to - 2.57, p = 0.00001), and the APACHE II scores (MD - 1.65, 95% CI: - 2.89 to - 0.63, p = 0.001). Additionally, the results showed that IgM-enriched IVIG was effective in treating sepsis (RR 0.55, 95% CI: 0.40 - 0.76; p = 0.0003), while standard IVIG failed to be effective (RR 0.91, 95% CI: 0.81-1.02, p = 0.10). And the effect of IVIG in reducing neonatal mortality was inconclusive (RR 0.93, 95% CI: 0.81-1.05, p = 0.24), but it played a large role in reducing sepsis mortality in adults (RR 0.70, 95% CI: 0.57-0.86, p = 0.0006). Besides, from the subgroup of different economic regions, it indicated that IVIG was effective for sepsis in high-income (RR 0.89, 95% CI: 0.79-0.99, p = 0.03) and middle-income countries (RR 0.49, 95% CI: 0.28-0.84, p = 0.01), while no benefit was demonstrated in low-income countries (RR 0.56, 95% CI: 0.27-1.14, p = 0.11). CONCLUSIONS: There is sufficient evidence to support that IVIG reduces sepsis mortality. IgM-enriched IVIG is effective in both adult and neonatal sepsis, while standard IVIG is only effective in adult sepsis. IVIG for sepsis has shown efficacy in high- and middle-income countries, but is still debatable in low-income countries. More RCTs are needed in the future to confirm the true clinical potential of IVIG for sepsis in low-income countries.

Mixing in Langmuir Monolayers: Perfluorotetradecanoic Acid and a Gemini Surfactant without a Linker.

A recently reported anionic gemini surfactant, a member of the so-called "gemini without a linker" family, has recently been reported to form closely packed crystalline monolayers at the air-water interface. In this work, the impact on monolayer properties of the compound, C18-0-C18, that result from its mixing with a benchmark perfluorinated surfactant, perfluorotetradecanoic acid (PF), is explored. The films exhibit nonideal mixing, as determined by surface pressure-area (π-A) isotherms and surface potential measurements, and phase-separation between the two components was observed by the direct visualization of the monolayers, and grazing-incident X-ray diffraction at the air-water interface. The pure and mixed films follow similar trends in the order of C18-0-C18 < PF < χPF = 0.50 mixed films for both their extent of hysteresis and their stability at the air-water interface. Further, crystallographic data for the mixed film emerge as a simple combination of distinct diffraction patterns characteristic of both the individual components, consistent with the other findings reported here and thus clarify the intermolecular behavior of the binary mixture at the surface.

Elevated temperature induces contrasting transformation of exogenous copper to soil solution and solid phases in an arable soil.

Heavy metal contamination of soils has been a global environmental issue over the past decades, threatening food security and human health. Understanding the migration and transformation of heavy metals in soils is critical for restoring an impaired environment and developing sustainable agriculture, particularly in the face of global warming. However, little effort has been devoted to investigating the impact of elevated temperatures on the migration and distribution of exogenous heavy metals in soils. This study experimented with a 180-day incubation at 15 °C, 30 °C, and 45 °C with an arable soil (Alfisol) of Huang-Huai-Hai River Basin, China, which was initially spiked with copper (Cu). A comparison of the results revealed that the percentage of soil water-soluble Cu doubled at 45 °C compared with 15 °C. The percentage of protein-like substances in dissolved organic matter (DOM) was the highest at 45 °C, suggesting that proteinaceous components play a more significant role in controlling the dissolution of Cu into DOM. Moreover, by sequential extraction and micro-X-ray fluorescence (µ-XRF), Cu was facilitatively transformed from exchangeable, and specifically adsorbed fractions, to iron (Fe)/manganese (Mn) oxides bound species by 7.75%23.63% with the elevation of temperature from 15 °C to 45 °C. The conversion of Cu speciation is attributed to the significant release of organic carbon from Fe/Mn oxides, especially the Mn oxide components, which are available for Cu binding. The findings of this work will provide an in-depth understanding of the fate of Cu in soils, which is fundamental for the risk assessment and remediation of Cu-polluted soils in the Huang-Huai-Hai River Basin under the context of global warming.

Inhibitory Mechanisms of Lekethromycin in Dog Liver Cytochrome P450 Enzymes Based on UPLC-MS/MS Cocktail Method.

Lekethromycin (LKMS) is a synthetic macrolide compound derivative intended for use as a veterinary medicine. Since there have been no in vitro studies evaluating its potential for drug-drug interactions related to cytochrome P450 (CYP450) enzymes, the effect of the inhibitory mechanisms of LKMS on CYP450 enzymes is still unclear. Thus, this study aimed to evaluate the inhibitory effects of LKMS on dog CYP450 enzymes. A cocktail approach using ultra-performance liquid chromatography-tandem mass spectrometry was conducted to investigate the inhibitory effect of LKMS on canine CYP450 enzymes. Typical probe substrates of phenacetin, coumarin, bupropion, tolbutamide, dextromethorphan, chlorzoxazone, and testosterone were used for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4, respectively. This study showed that LKMS might not be a time-dependent inhibitor. LKMS inhibited CYP2A6, CYP2B6, and CYP2D6 via mixed inhibition. LKMS exhibited mixed-type inhibition against the activity of CYP2A6 with an inhibition constant (Ki) value of 135.6 µΜ. LKMS inhibited CYP2B6 in a mixed way, with Ki values of 59.44 µM. A phenotyping study based on an inhibition assay indicated that CYP2D6 contributes to the biotransformation of LKMS. A mixed inhibition of CYP2D6 with Ki values of 64.87 µM was also observed. Given that this study was performed in vitro, further in vivo studies should be conducted to identify the interaction between LKMS and canine CYP450 enzymes to provide data support for the clinical application of LKMS and the avoidance of adverse interactions between other drugs.

Atomically Precise Copper Nanoclusters for Highly Efficient Electroreduction of CO2 towards Hydrocarbons via Breaking the Coordination Symmetry of Cu Site.

We propose an effective highest occupied d-orbital modulation strategy engendered by breaking the coordination symmetry of sites in the atomically precise Cu nanocluster (NC) to switch the product of CO2 electroreduction from HCOOH/CO to higher-valued hydrocarbons. An atomically well-defined Cu6 NC with symmetry-broken Cu-S2 N1 active sites (named Cu6 (MBD)6 , MBD=2-mercaptobenzimidazole) was designed and synthesized by a judicious choice of ligand containing both S and N coordination atoms. Different from the previously reported high HCOOH selectivity of Cu NCs with Cu-S3 sites, the Cu6 (MBD)6 with Cu-S2 N1 coordination structure shows a high Faradaic efficiency toward hydrocarbons of 65.5 % at -1.4 V versus the reversible hydrogen electrode (including 42.5 % CH4 and 23 % C2 H4 ), with the hydrocarbons partial current density of -183.4 mA cm-2 . Theoretical calculations reveal that the symmetry-broken Cu-S2 N1 sites can rearrange the Cu 3d orbitals with d x 2 - y 2 ${d_{x^2 - y^2 } }$ as the highest occupied d-orbital, thus favoring the generation of key intermediate *COOH instead of *OCHO to favor *CO formation, followed by hydrogenation and/or C-C coupling to produce hydrocarbons. This is the first attempt to regulate the coordination mode of Cu atom in Cu NCs for hydrocarbons generation, and provides new inspiration for designing atomically precise NCs for efficient CO2 RR towards highly-valued products.

Physicochemical Properties of Monolayers of a Gemini Surfactant with a Minimal-Length Spacer.

Fundamental physical chemical properties of monolayers formed from a new anionic gemini surfactant with a minimal-length (single-bond) spacer unit have been investigated at the air-water interface and compared with those of monolayers formed from affiliated comparator surfactants. The minimal spacer surfactant, dubbed C18-0-C18, exhibited strikingly different packing characteristics from an anionic gemini surfactant with a comparatively bulkier headgroup, including the formation of close-packed, crystalline films, and shared similar characteristics to simple fatty acid-based monolayers. Monolayers of C18-0-C18 also exhibited good stability at the air-water interface and transferred with reasonable efficiency to solid substrates, although the film integrity was compromised during the transfer. Results from this work suggest that the single-bond spacer approach might be more broadly useful for designing gemini surfactants that pack efficiently into ordered monolayers.

Free Thiols Regulate the Interactions and Self-Assembly of Thiol-Passivated Metal Nanoparticles.

Thiol ligands bound to the metallic core of nanoparticles determine their interactions with the environment and self-assembly. Recent studies suggest that equilibrium between bound and free thiols alters the ligand coverage of the core. Here, X-ray scattering and MD simulations investigate water-supported monolayers of gold-core nanoparticles as a function of the core-ligand coverage that is varied in experiments by adjusting the concentration of total thiols (sum of free and bound thiols). Simulations demonstrate that the presence of free thiols produces a nearly symmetrical coating of ligands on the core. X-ray measurements show that above a critical value of core-ligand coverage the nanoparticle core rises above the water surface, the edge-to-edge distance between neighboring nanoparticles increases, and the nanoparticle coverage of the surface decreases. These results demonstrate the important role of free thiols: they regulate the organization of bound thiols on the core and the interactions of nanoparticles with their surroundings.

GDF11 Regulates PC12 Neural Stem Cells via ALK5-Dependent PI3K-Akt Signaling Pathway.

Growth differentiation factor 11 (GDF11), belonging to the transforming factor-ß superfamily, regulates anterior-posterior patterning and inhibits neurogenesis during embryonic development. However, recent studies recognized GDF11 as a rejuvenating (or anti-ageing) factor to reverse age-related cardiac hypertrophy, repair injured skeletal muscle, promote cognitive function, etc. The effects of GDF11 are contradictory and the mechanism of action is still not well clarified. The objective of the present study was to investigate effects of GDF11 on PC12 neural stem cells in vitro and to reveal the underlying mechanism. We systematically assessed the effects of GDF11 on the life activities of PC12 cells. GDF11 significantly suppressed cell proliferation and migration, promoted differentiation and apoptosis, and arrested cell cycle at G2/M phase. Both TMT-based proteomic analysis and phospho-antibody microarray revealed PI3K-Akt pathway was enriched when treated with GDF11. Inhibition of ALK5 or PI3K obviously attenuated the effects of GDF11 on PC12 neural stem cells, which exerted that GDF11 regulated neural stem cells through ALK5-dependent PI3K-Akt signaling pathway. In summary, these results demonstrated GDF11 could be a negative regulator for neurogenesis via ALK5 activating PI3K-Akt pathway when it directly acted on neural stem cells.

Real-Time Fluorescent Monitoring of Kinetically Controlled Supramolecular Self-Assembly of Atom-Precise Cu8 Nanocluster.

Kinetically stable and long-lived intermediates are crucial in monitoring the progress and understanding of supramolecular self-assembly of diverse aggregated structures with collective functions. Herein, the complex dynamics of an atomically precise CuI nanocluster [Cu8 (t BuC6 H4 S)8 (PPh3 )4 ] (Cu8a) is systematically investigated. Remarkably, by monitoring the aggregation-induced emission (AIE) and electron microscopy of the kinetically stable intermediates in real time, the directed self-assembly (DSA) process of Cu8a is deduced. The polymorphism and different emission properties of Cu NCs aggregates were successfully captured, allowing the structure-optical property relationship to be established. More importantly, the utilization of a mathematical "permutation and combination" ideology by introducing a heterogeneous luminescent agent of a carbon dot (CD) to Cu8a aggregates enriches the "visualization" fluorescence window, which offers great potential in real time application for optical sensing of materials.

Demographic Characteristics and Lifestyle Habits of Chinese Plasma Donors: A Multicenter Study.

BACKGROUND The demand for plasma and plasma products has increased in China, which has a short supply. Compared with whole blood donors, plasma donors and their donation behavior have received less attention. This study aimed to investigate the demographic characteristics and lifestyle habits of Chinese plasma donors. MATERIAL AND METHODS During 2018-2019, information on plasma donors was collected from blood product companies using a 25-item questionnaire, including sex, age, height, weight, blood group, donation frequency, occupation, smoking and drinking, and sleeping and dietary habits. RESULTS Among 15 497 plasma donors, 70.5% were women and 78.5% were aged 46-55 years. Among 4847 plasma donors, the average height of men was 169.5±6.2 cm and the average height of women was 157.0±4.6 cm. In addition, the average weight of men was 67.0±10.4 kg and the average weight of women was 60.0±8.3 kg. The prevalence of obesity (body mass index ≥30.0 kg/m²) of all donors was 14.8%; 14.7% of men were obese, and 15% of women were obese. Among all plasma donors, 88.8% were farmers and 60% were frequent donors with a donation history of at least 5 years. Among all donors, 84.0% did not smoke, 67.3% did not drink, and 95.1% reported good sleep quality. All respondents reported healthy dietary habits. CONCLUSIONS Healthy lifestyle habits considerably affect the health of plasma donors and the quality of source plasma. Chinese plasma donors in this study demonstrated imbalances in terms of characteristics, which became more marked with age.

Age-related gene expression and DNA methylation changes in rhesus macaque.

Aging is a very complicated biological process that can change gene expressions. The Chinese rhesus macaque (Macaca mulatta lasiota; CR) is closely related to humans. We explored gene expression with increasing age and DNA methylation changes in young and old CRs. Results showed blood transcriptome and DNA methylome significantly changed from young to old CRs. The age-associated differentially expressed genes (DEGs) and differentially methylated regions (DMRs) were associated with age-related biological features, such as immunity, blood coagulation, and biosynthetic process. The measurements of coagulation indicators confirmed old CRs had shorter coagulation time than young CRs, and the activities of coagulation factor II (FII) and factor VIII (FVIII) were enhanced in old CRs. Humans and CRs exhibited the same enhanced blood coagulation with age phenotype. Our study found aging is a critical factor affecting gene expression in CRs, and also provided new insights into the blood coagulation changes in non-human primates.

The bioavailability and pharmacokinetics of an amoxicillin-clavulanic acid granular combination after intravenous and oral administration in swine.

The pharmacokinetic behaviours of amoxicillin (AMX) and clavulanic acid (CA) in swine were studied after either an intravenous or oral administration of AMX (10 mg/kg) and CA (2.5 mg/kg). The concentrations of these two medicines in swine plasma were determined using high-performance liquid chromatographic-tandem mass spectrometry, and the data were analysed using a noncompartmental model with the WinNonlin software. After intravenous administration, both substances were absorbed rapidly and reached their effective therapeutic concentration quickly. CA was eliminated more slowly compared with AMX. Moreover, the distribution volume of AMX was larger than that of CA, suggesting that AMX could penetrate tissues better. After oral administration of the granular formulation, no significant difference was observed in the mean elimination half-life value between AMX and CA. The mean maximal plasma concentrations of AMX and CA, reached after 1.14 and 1.32 hr, were 2.58 and 1.91 µg/m, respectively. The mean oral bioavailability of AMX and CA was 23.6% and 26.4%, respectively. After oral administration, the T>MIC50 for three common respiratory pathogens was over 6.12 hr. Therefore, oral administration could be more effective in the clinical therapy of pigs, especially when administered twice daily.