Pretreatment and analysis techniques development of TKIs in biological samples for pharmacokinetic studies and therapeutic drug monitoring.

Tyrosine kinase inhibitors (TKIs) have emerged as the first-line small molecule drugs in many cancer therapies, exerting their effects by impeding aberrant cell growth and proliferation through the modulation of tyrosine kinase-mediated signaling pathways. However, there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites, which may render patients with compromised immune function susceptible to diverse infections despite receiving theoretically efficacious anticancer treatments, alongside other potential side effects or adverse reactions. Therefore, an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods, clinical pharmacokinetics, and therapeutic drug monitoring of different TKIs. This paper provides a comprehensive overview of the advancements in pretreatment methods, such as protein precipitation (PPT), liquid-liquid extraction (LLE), solid-phase extraction (SPE), micro-SPE (µ-SPE), magnetic SPE (MSPE), and vortex-assisted dispersive SPE (VA-DSPE) achieved since 2017. It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography (HPLC) and high-resolution mass spectrometry (HRMS) methods, capillary electrophoresis (CE), gas chromatography (GC), supercritical fluid chromatography (SFC) procedures, surface plasmon resonance (SPR) assays as well as novel nanoprobes-based biosensing techniques. In addition, a comparison is made between the advantages and disadvantages of different approaches while presenting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

Photothermal-Responsive Lightweight Hydrogel Actuator Loaded with Polydopamine-Modified Hollow Glass Microspheres.

Aquatic actuators based on the light-to-work conversion are of paramount significance for the development of cutting-edge fields including robots, micromachines, and intelligent systems. Herein, we report the design and synthesis of near-infrared light-driven hydrogel actuators through loading with lightweight polydopamine-modified hollow glass microspheres (PDA-HGMPs) into responsive poly(N-isopropylacrylamide) (PNIPAM) hydrogels. These PDA-HGMPs can not only function as an excellent photothermal agent but also accelerate the swelling/desewlling of hydrogels due to their reconstruction for polymer gel skeleton, which speeds up the response rate of hydrogel actuators. The resulting hydrogel actuator shows controlled movements under light illumination, including complex self-propellant and floating/sinking motions. As the proof-of-concept demonstrations, a self-sensing robot is conceptualized by integrating the PDA-HGMP-containing hydrogel actuator with an ultrathin and miniature pressure sensor. Hopefully, this work can offer some important insights into the research of smart aquatic soft actuators, paving the way to the potential applications in emerging fields including micromachines and intelligent systems.

[Methods for traditional Chinese medicine syndrome-based efficacy evaluation: a review].

Traditional Chinese medicine(TCM) syndrome-based efficacy is an evaluation index which is unique to TCM and can reflect the advantages of TCM. The development of the methods and measurement tools for evaluating TCM syndrome-based efficacy can provide objective and quantitative evidence for the clinical efficacy evaluation of TCM and the development of new Chinese medicine preparations, being the exploration direction of innovative methods and technologies for evaluating TCM efficacy. The conventional evaluation methods are subjective and limited to the mitigation of symptoms and the improvement of physical signs, which make it difficult to form a unified evaluation standard. In addition, the evaluation methods lack unity, objectivity, and quantitative research. The scientific connotation, evaluation ideas and methods, and key technologies of the evaluation for the therapeutic effect on syndromes remain unclear, which leads to diverse evaluation modes, methods, and indexes. The syndrome-based efficacy scale provides a new idea for the objective quantification and standardization of TCM syndromes. This review systematically summarizes the methods and problems, introduces the research progress in the evaluation scales, and puts forward some thoughts on the characteristics of TCM syndrome-based efficacy evaluation, aiming to provide insights for the research in this field.

Analysis of blood biochemistry and non-targeted metabolomics of endometritis in dairy cows.

The incidence of bovine endometritis, which has a negative impact on the reproduction of dairy cows, has been recently increasing. In this study, the differential markers and metabolites of healthy cows and cows with endometritis were analyzed by measuring blood biochemical indicators and immune factors using biochemical and enzyme-linked immunosorbent assay kits combined with nontargeted metabolomics. The LC-QTOF platform was used to evaluate the serum metabolomics of healthy cows and cows with endometritis after 21-27 days of calving. The results showed that glucose, free fatty acid, calcium, sodium, albumin, and alanine aminotransferase levels were significantly lower in the serum of cows with endometritis than in healthy cows (P < 0.05). However, the serum potassium, interleukin-1, interleukin-6, and tumor necrosis factor levels were significantly higher in cows with endometritis (P < 0.05). In addition, the serum metabolome data analysis of the two groups showed that the expression of 468 metabolites was significantly different (P < 0.05), of which 291 were upregulated and 177 were downregulated. These metabolites were involved in 78 metabolic pathways, including amino acid, nucleotide, carbohydrate, lipid, and vitamin metabolism pathways; signal transduction pathways, and other biological pathways. Taken together, negative energy balance and immune activation, which are related to local abnormalities in amino acid, lipid, and carbohydrate metabolism, were the important causes of endometritis in dairy cows. Metabolites such as glucose, carnosine, dehydroascorbic acid, L-malic acid, tetrahydrofolic acid, and UDP-glucose may be used as key indicators in the hematological diagnosis and treatment of endometritis in dairy cows.

Transcriptomic and metabolomic profiling provide insight into the role of sugars and hormones in leaf senescence of Pinellia ternata.

KEY MESSAGE: The interaction network and pathway map uncover the potential crosstalk between sugar and hormone metabolisms as a possible reason for leaf senescence in P. ternata. Pinellia ternata, an environmentally sensitive medicinal plant, undergoes leaf senescence twice a year, affecting its development and yield. Understanding the potential mechanism that delays leaf senescence could theoretically decrease yield losses. In this study, a typical senescent population model was constructed, and an integrated analysis of transcriptomic and metabolomic profiles of P. ternata was conducted using two early leaf senescence populations and two stay-green populations. The result showed that two key gene modules were associated with leaf senescence which were mainly enriched in sugar and hormone signaling pathways, respectively. A network constructed by unigenes and metabolisms related to the obtained two pathways revealed that several compounds such as D-arabitol and 2MeScZR have a higher significance ranking. In addition, a total of 130 hub genes in this network were categorized into 3 classes based on connectivity. Among them, 34 hub genes were further analyzed through a pathway map, the potential crosstalk between sugar and hormone metabolisms might be an underlying reason of leaf senescence in P. ternata. These findings address the knowledge gap regarding leaf senescence in P. ternata, providing candidate germplasms for molecular breeding and laying theoretical basis for the realization of finely regulated cultivation in future.

Optineurin-facilitated axonal mitochondria delivery promotes neuroprotection and axon regeneration.

Optineurin (OPTN) mutations are linked to amyotrophic lateral sclerosis (ALS) and normal tension glaucoma (NTG), but a relevant animal model is lacking, and the molecular mechanisms underlying neurodegeneration are unknown. We found that OPTN C-terminus truncation (OPTN∆C) causes late-onset neurodegeneration of retinal ganglion cells (RGCs), optic nerve (ON), and spinal cord motor neurons, preceded by a striking decrease of axonal mitochondria. Surprisingly, we discover that OPTN directly interacts with both microtubules and the mitochondrial transport complex TRAK1/KIF5B, stabilizing them for proper anterograde axonal mitochondrial transport, in a C-terminus dependent manner. Encouragingly, overexpressing OPTN/TRAK1/KIF5B reverses not only OPTN truncation-induced, but also ocular hypertension-induced neurodegeneration, and promotes striking ON regeneration. Therefore, in addition to generating new animal models for NTG and ALS, our results establish OPTN as a novel facilitator of the microtubule-dependent mitochondrial transport necessary for adequate axonal mitochondria delivery, and its loss as the likely molecular mechanism of neurodegeneration.

Effects of Lactobacillus paracasei N1115 on gut microbial imbalance and liver function in patients with hepatitis B-related cirrhosis.

BACKGROUND: Hepatitis B cirrhosis (HBC) is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic dysfunction. Although the relationship between certain single probiotics and HBC has been explored, the impact of the complex ready-to-eat Lactobacillus paracasei N1115 (LP N1115) supplement on patients with HBC has not been determined. AIM: To compare the changes in the microbiota, inflammatory factor levels, and liver function before and after probiotic treatment in HBC patients. METHODS: This study included 160 HBC patients diagnosed at the General Hospital of Ningxia Medical University between October 2018 and December 2020. Patients were randomly divided into an intervention group that received LP N1115 supplementation and routine treatment and a control group that received routine treatment only. Fecal samples were collected at the onset and conclusion of the 12-wk intervention period. The structure of the intestinal microbiota and the levels of serological indicators, such as liver function and inflammatory factors, were assessed. RESULTS: Following LP N1115 intervention, the intestinal microbial diversity significantly increased in the intervention group (P < 0.05), and the structure of the intestinal microbiota was characterized by an increase in the proportions of probiotic microbes and a reduction in harmful bacteria. Additionally, the intervention group demonstrated notable improvements in liver function indices and significantly lower levels of inflammatory factors (P < 0.05). CONCLUSION: LP N1115 is a promising treatment for ameliorating intestinal microbial imbalance in HBC patients by modulating the structure of the intestinal microbiota, improving liver function, and reducing inflammatory factor levels.

HOXA9 gene inhibits proliferation and differentiation and promotes apoptosis of bovine preadipocytes.

BACKGROUND: Hox gene family is an important transcription factor that regulates cell process, and plays a role in the process of adipocytes differentiation and fat deposition. Previous transcriptome sequencing studies have indicated that the Homeobox A9 gene (HOXA9) is a candidate gene for regulating the process of bovine lipid metabolism, but the function and specific mechanism of action remain unclear. Therefore, this study aims to explore the role of HOXA9 in the proliferation, differentiation and apoptosis of bovine preadipocytes through gain-of-function and lose-of-function. RESULT: It found HOXA9 highly expressed in bovine adipose tissue, and its expression level changed significantly during adipocytes differentiation process. It gave a hint that HOXA9 may be involved in the process of bovine lipid metabolism. The results of HOXA9 gain-of-function experiments indicated that HOXA9 appeared to act as a negative regulator not only in the differentiation but also in the proliferation of bovine preadipocytes, which is mainly reflected that overexpression of HOXA9 down-regulate the mRNA and protein expression level of PPARγ, CEBPα and FABP4 (P < 0.05). The mRNA expression level of CDK1, CDK2, PCNA, CCNA2, CCNB1, CCND1 and CCNE2, as well as the protein expression of CDK2 also significantly decreased. The decrease of lipid droplets content was the main characteristic of the phenotype (P < 0.01), which further supported the evidence that HOXA9 was a negative regulator of preadipocytes differentiation. The decrease of cell proliferation rate and EdU positive rate, as well as the limitation of transition of preadipocytes from G0/G1 phase to S phase also provided evidence for the inhibition of proliferation. Apart from this above, we noted an interesting phenomenon that overexpression of HOXA9 showed in a significant upregulation of both mRNA and protein level of apoptosis markers, accompanied by a significant increase in cell apoptosis rate. These data led us not to refute the fact that HOXA9 played an active regulatory role in apoptosis. HOXA9 loss-of-function experiments, however, yielded the opposite results. Considering that HOXA9 acts as a transcription factor, we predicted its target genes. Dual luciferase reporter assay system indicated that overexpression of HOXA9 inhibits activity of PCNA promoter. CONCLUSION: Taken together, we demonstrated for the first time that HOXA9 played a role as a negative regulatory factor in the differentiation and proliferation of preadipocytes, but played a positive regulatory role in apoptosis, and it may play a regulatory role by targeting PCNA. This study provides basic data for further exploring the regulatory network of intramuscular fat deposition in bovine.

Global research hotspots, development trends and prospect discoveries of phase separation in cancer: a decade-long informatics investigation.

Liquid-liquid phase separation (LLPS) is a complex and subtle phenomenon whose formation and regulation take essential roles in cancer initiation, growth, progression, invasion, and metastasis. This domain holds a wealth of underutilized unstructured data that needs further excavation for potentially valuable information. Therefore, we retrospectively analyzed the global scientific knowledge in the field over the last decade by using informatics methods (such as hierarchical clustering, regression statistics, hotspot burst, and Walktrap algorithm analysis). Over the past decade, this area enjoyed a favorable development trend (Annual Growth Rate: 34.98%) and global collaboration (International Co-authorship: 27.31%). Through unsupervised hierarchical clustering based on machine learning, the global research hotspots were divided into five dominant research clusters: Cluster 1 (Effects and Mechanisms of Phase Separation in Drug Delivery), Cluster 2 (Phase Separation in Gene Expression Regulation), Cluster 3 (Phase Separation in RNA-Protein Interaction), Cluster 4 (Reference Value of Phase Separation in Neurodegenerative Diseases for Cancer Research), and Cluster 5 (Roles and Mechanisms of Phase Separation). And further time-series analysis revealed that Cluster 5 is the emerging research cluster. In addition, results from the regression curve and hotspot burst analysis point in unison to super-enhancer (a=0.5515, R2=0.6586, p=0.0044) and stress granule (a=0.8000, R2=0.6000, p=0.0085) as the most potential star molecule in this field. More interestingly, the Random-Walk-Strategy-based Walktrap algorithm further revealed that "phase separation, cancer, transcription, super-enhancer, epigenetics"(Relevance Percentage[RP]=100%, Development Percentage[DP]=29.2%), "stress granule, immunotherapy, tumor microenvironment, RNA binding protein"(RP=79.2%, DP=33.3%) and "nanoparticle, apoptosis"(RP=70.8%, DP=25.0%) are closely associated with this field, but are still under-developed and worthy of further exploration. In conclusion, this study profiled the global scientific landscape, discovered a crucial emerging research cluster, identified several pivotal research molecules, and predicted several crucial but still under-developed directions that deserve further research, providing an important reference value for subsequent basic and clinical research of phase separation in cancer.

Novel 3D MRI-Based Volumetric Assessment of Rotator Cuff Musculature Demonstrates Stronger Correlation with Preoperative Functional Status When Compared to the Goutallier Grading Scheme.

BACKGROUND: The Goutallier classification (GC) is used to assess fatty atrophy in rotator cuff (RC) tears, yet limitations exist. A battery of 3D-magnetic resonance imaging (MRI) volumetric scores (VS) was developed to provide comprehensive characterization of RC pathology. The purposes of this study were to: (1) Describe the correlation between GC and VS for supraspinatus changes in RC tears, (2) Characterize the chronicity of RC tears using the battery of 12 VS measurements, and (3) Compare GC and VS to determine which method most closely corresponds with preoperative patient reported outcome measures (PROMs). METHODS: Preoperative shoulder MRIs were reviewed after arthroscopic RC repair. Preoperative GC stage and Patient-Reported Outcomes Measurement Information System (PROMIS) physical function (PF) and pain interference (PI) scores were collected. The battery of VS included fat infiltration (FIS), muscle size (MSS) and relative volume contribution (RCS) for each RC muscle. Backwards linear regression was performed to compare GC stage with preoperative PROMIS PF/PI to determine which VS measurement most closely correlated with preoperative PROMs. RESULTS: Eighty-two patients underwent RC repair (mean age 55±8.2 years, 63% male, 68% GC stage ≤1). In evaluation of the supraspinatus, there was a moderate positive correlation between GC and FIS (r = 0.459, p < 0.001); strong negative correlations were observed between MSS (r = -0.800, p < 0.001) and RCS (r = -0.745, p < 0.001) when compared to GC. A negligible linear correlation was observed between GC and preoperative PROMIS PF (r = -0.106, p = 0.343) and PI (r = -0.071, p = 0.528). On multivariate analysis, subscapularis MSS (beta > 0, p = 0.064) was a positive predictor, and subscapularis FIS (beta < 0, p = 0.137), teres minor MSS (beta < 0, p = 0.141) and FIS (beta < 0, p = 0.070) were negative predictors of preoperative PF (r = 0.343, p = 0.044); while supraspinatus MSS (beta > 0, p = 0.009) and FIS (beta > 0, p = 0.073), teres minor FIS (beta > 0, p = 0.072) and subscapularis FIS (beta > 0, p = 0.065) were positive predictors of preoperative PI (r = 0.410, p = 0.006). CONCLUSION: Although gold standard in evaluation of RC pathology, GC demonstrated negligible correlation with preoperative functional disability. Alternatively, a battery of 3D VS showed strong correlation with GC through a quantitative, comprehensive evaluation of the RC unit including several moderate predictors of preoperative functional disability.

Mitigating the Overheat of Stretchable Electronic Devices Via High-Enthalpy Thermal Dissipation of Hydrogel Encapsulation.

The practical application of flexible and stretchable electronics is significantly influenced by their thermal and chemical stability. Elastomer substrates and encapsulation, due to their soft polymer chains and high surface-area-to-volume ratio, are particularly susceptible to high temperatures and flame. Excessive heat poses a severe threat of damage and decomposition to these elastomers. By leveraging water as a high enthalpy dissipating agent, here, a hydrogel encapsulation strategy is proposed to enhance the flame retardancy and thermal stability of stretchable electronics. The hydrogel-based encapsulation provides thermal protection against flames for more than 10 s through the evaporation of water. Further, the stretchability and functions automatically recover by absorbing air moisture. The incorporation of hydrogel encapsulation enables stretchable electronics to maintain their functions and perform complex tasks, such as fire saving in soft robotics and integrated electronics sensing. With high enthalpy heat dissipation, encapsulated soft electronic devices are effectively shielded and retain their full functionality. This strategy offers a universal method for flame retardant encapsulation of stretchable electronic devices.

Effect of Al/Ni Ratio on the Microstructure and Properties of Nickel-Aluminum Bronze Alloys.

To study the effect of aluminum and nickel elements on the microstructures and properties of the nickel-aluminum bronze (NAB) alloy, four kinds of alloys with different compositions, ZCuAl7-7-4-2, ZCuAl8-6-4-2, ZCuAl9-5-4-2, and ZCuAl10-4-4-2, are prepared by vacuum-melting technology. The effects of different Al/Ni ratios on the microstructures of NAB are investigated using a metalloscope, scanning electron microscopy, transmission electron microscopy, and XPS analysis. The mechanical property is evaluated with microhardness testing and tensile mechanical testing. The corrosion resistance is evaluated using mass-loss testing, electrochemical testing, and corrosion-product characterization. The results show that with the increase of the Al/Ni ratio, the content of precipitated phases increases, while ß' and hard κ, which have a different morphology, appear. As the Al/Ni ratio rises from 1 to 2.5, the hardness increases from 104 HV to 202 HV, and the tensile strength increases by 394 MPa from 356 MPa to 751 MPa, but the elongation decreases substantially from 50.50% to 11.00%. The best corrosion resistance is shown on ZCuAl7-7-4-2, with a corrosion rate of 0.00267 mm/a after 30 d of static immersion corrosion in 3.5 wt.% NaCl solution. Through electrochemical testing and corrosion-product characterization, it is found that ZCuAl7-7-4-2 has the largest polarization resistance Rp, and the selective corrosion of the surface is mild.

Active Learning in Brain Tumor Segmentation with Uncertainty Sampling and Annotation Redundancy Restriction.

Deep learning models have demonstrated great potential in medical imaging but are limited by the expensive, large volume of annotations required. To address this, we compared different active learning strategies by training models on subsets of the most informative images using real-world clinical datasets for brain tumor segmentation and proposing a framework that minimizes the data needed while maintaining performance. Then, 638 multi-institutional brain tumor magnetic resonance imaging scans were used to train three-dimensional U-net models and compare active learning strategies. Uncertainty estimation techniques including Bayesian estimation with dropout, bootstrapping, and margins sampling were compared to random query. Strategies to avoid annotating similar images were also considered. We determined the minimum data necessary to achieve performance equivalent to the model trained on the full dataset (α = 0.05). Bayesian approximation with dropout at training and testing showed results equivalent to that of the full data model (target) with around 30% of the training data needed by random query to achieve target performance (p = 0.018). Annotation redundancy restriction techniques can reduce the training data needed by random query to achieve target performance by 20%. We investigated various active learning strategies to minimize the annotation burden for three-dimensional brain tumor segmentation. Dropout uncertainty estimation achieved target performance with the least annotated data.

Topologically Protected Quantum Logic Gates with Valley-Hall Photonic Crystals.

Topological photonics provide a promising way to realize more robust optical devices against some defects and environmental perturbations. Quantum logic gates are fundamental units of quantum computers, which are widely used in future quantum information processing. Thus, constructing robust universal quantum logic gates is an important way forward to practical quantum computing. However, the most important problem to be solved is how to construct the quantum-logic-gate-required 2 × 2 beam splitter with topological protection. Here, the experimental realization of the topologically protected contradirectional coupler is reported, which can be employed to realize the quantum logic gates, including control-NOT and Hadamard gates, on the silicon photonic platform. These quantum gates not only have high experimental fidelities but also exhibit a certain degree of tolerances against certain types of defects. This work paves the way for the development of practical optical quantum computations and signal processing.

Pivotal role of heterotrimeric G protein in the crosstalk between sugar signaling and abiotic stress response in plants.

Heterotrimeric G-proteins are key modulators of multiple signaling and developmental pathways in plants, in which they act as molecular switches to engage in transmitting various stimuli signals from outside into the cells. Substantial studies have identified G proteins as essential components of the organismal response to abiotic stress, leading to adaptation and survival in plants. Meanwhile, sugars are also well acknowledged key players in stress perception, signaling, and gene expression regulation. Connections between the two significant signaling pathways in stress response are of interest to a general audience in plant biology. In this article, advances unraveling a pivotal role of G proteins in the process of sugar signals outside the cells being translated into the operation of autophagy in cells during stress are reviewed. In addition, we have presented recent findings on G proteins regulating the response to drought, salt, alkali, cold, heat and other abiotic stresses. Perspectives on G-protein research are also provided in the end. Since G protein signaling regulates many agronomic traits, elucidation of detailed mechanism of the related pathways would provide useful insights for the breeding of abiotic stress resistant and high-yield crops.

Pulmonary MRI with hyperpolarized xenon-129 demonstrates novel alterations in gas transfer across the air-blood barrier in asthma.

BACKGROUND: Individuals with asthma can vary widely in clinical presentation, severity, and pathobiology. Hyperpolarized xenon-129 (Xe129) MRI is a novel imaging method to provide 3-D mapping of both ventilation and gas exchange in the human lung. PURPOSE: To evaluate the functional changes in adults with asthma as compared to healthy controls using Xe129 MRI. METHODS: All subjects (20 controls and 20 asthmatics) underwent lung function measurements and Xe129 MRI on the same day. Outcome measures included the pulmonary ventilation defect and transfer of inspired Xe129 into two soluble compartments: tissue and blood. Ten asthmatics underwent Xe129 MRI before and after bronchodilator to test whether gas transfer measures change with bronchodilator effects. RESULTS: Initial analysis of the results revealed striking differences in gas transfer measures based on age, hence we compared outcomes in younger (n = 24, ≤ 35 years) versus older (n = 16, > 45 years) asthmatics and controls. The younger asthmatics exhibited significantly lower Xe129 gas uptake by lung tissue (Asthmatic: 0.98% ± 0.24%, Control: 1.17% ± 0.12%, P = 0.035), and higher Xe129 gas transfer from tissue to the blood (Asthmatic: 0.40 ± 0.10, Control: 0.31% ± 0.03%, P = 0.035) than the younger controls. No significant difference in Xe129 gas transfer was observed in the older group between asthmatics and controls (P > 0.05). No significant change in Xe129 transfer was observed before and after bronchodilator treatment. CONCLUSIONS: By using Xe129 MRI, we discovered heterogeneous alterations of gas transfer that have associations with age. This finding suggests a heretofore unrecognized physiological derangement in the gas/tissue/blood interface in young adults with asthma that deserves further study.

Atmospheric CO2 and 14CO2 observations at the northern foot of the Qinling Mountains in China: Temporal characteristics and source quantification.

A two-year (March 2021 to February 2023) continuous atmospheric CO2 and a one-year regular atmospheric 14CO2 measurement records were measured at the northern foot of the Qinling Mountains in Xi'an, China, aiming to study the temporal characteristics of atmospheric CO2 and the contributions from the sources of fossil fuel CO2 (CO2ff) and biological CO2 (CO2bio) fluxes. The two-year mean CO2 mole fraction was 442.2 ± 16.3 ppm, with a yearly increase of 4.7 ppm (i.e., 1.1 %) during the two-year observations. Seasonal CO2 mole fractions were the highest in winter (452.1 ± 17.7 ppm) and the lowest in summer (433.5 ± 13.3 ppm), with the monthly CO2 levels peaking in January and troughing in June. Diurnal CO2 levels peaked at dawn (05:00-07:00) in spring, summer and autumn, and at 10:00 in winter. 14C analysis revealed that the excess CO2 (CO2ex, atmospheric CO2 minus background CO2) at this site was mainly from CO2ff emissions (67.0 ± 26.8 %), and CO2ff mole fractions were the highest in winter (20.6 ± 17.7 ppm). Local CO enhancement above the background mole fraction (ΔCO) was significantly (r = 0.74, p < 0.05) positively correlated with CO2ff in a one-year measurement, and ΔCO:CO2ff showed a ratio of 23 ± 6 ppb/ppm during summer and winter sampling days, much lower than previous measurements and suggesting an improvement in combustion efficiency over the last decade. CO2bio mole fractions also peaked in winter (14.2 ± 9.6 ppm), apparently due to biomass combustion and the lower and more stable wintertime atmospheric boundary layer. The negative CO2bio values in summer indicated that terrestrial vegetation of the Qinling Mountains had the potential to uptake atmospheric CO2 during the corresponding sampling days. This site is most sensitive to local emissions from Xi'an and to short distance transportation from the southern Qinling Mountains through the valleys.

Ocean acidification alters shellfish-algae nutritional value and delivery.

The ecological effects of climate change and ocean acidification (OA) have been extensively studied. Various microalgae are ecologically important in the overall pelagic food web as key contributors to oceanic primary productivity. Additionally, no organism exists in isolation in a complex environment, and shifts in food quality may lead to indirect OA effects on consumers. This study aims to investigate the potential effects of OA on algal trophic composition and subsequent bivalve growth. Here, the growth and nutrient fractions of Chlorella sp., Phaeodactylum tricornutum and Chaetocetos muelleri were used to synthesize and assess the impact of OA on primary productivity. Total protein content, total phenolic compounds, and amino acid (AA) and fatty acid (FA) content were evaluated as nutritional indicators. The results demonstrated that the three microalgae responded positively to OA in the future environment, significantly enhancing growth performance and nutritional value as a food source. Additionally, certain macromolecular fractions found in consumers are closely linked to their dietary sources, such as phenylalanine, C14:0, C16:0, C16:1, C20:1n9, C18:0, and C18:3n. Our findings illustrate that OA affects a wide range of crucial primary producers in the oceans, which can disrupt nutrient delivery and have profound impacts on the entire marine ecosystem and human food health.

Guhan Yangsheng Jing mitigates hippocampal neuronal pyroptotic injury and manifies learning and memory capabilities in sleep deprived mice via the NLRP3/Caspase1/GSDMD signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Guhan Yangsheng Jing (GHYSJ) is a traditional Chinese patent medicine, that has the function of nourishing the kidney and replenishing the essence, invigorating the brain and calming the mind. It is often used to treat dizziness, memory loss, sleep disorders, fatigue, and weakness, etc. However, its mechanism for improving sleep has not yet been determined. AIM OF THE STUDY: This study aims to explore the effects of GHYSJ on Sleep Deprivation (SD)-induced hippocampal neuronal pyroptotic injury, learning and cognitive abilities, and sleep quality in mice. METHODS: In this study, a PCPA-induced SD mouse model was established. We assessed the influence of GHYSJ on sleep quality and mood by using the pentobarbital-induced sleep test (PIST) and sucrose preference test (SPT). The pharmacological effects of GHYSJ on learning and memory impairment were evaluated by the Morris Water Maze (MWM) and Open Field Test (OFT). Pathological changes in the hippocampal tissue of the SD rats were observed via HE staining and Nissl staining. The severity of neuronal damage was evaluated by detecting the expression of the neuronal marker Microtubule-associated protein 2 (MAP2), via immunohistochemistry and immunofluorescence. Furthermore, the levels of neurotransmitter 5-hydroxytryptophan (5-HTP), 5-hydroxy tryptamine (5-HT), γ-aminobutyric acid (GABA), and Glutamic acid (Glu) in hippocampal tissues, as well as the expression of inflammatory factors Interleukin-1ß (IL-1ß) and Interleukin-18 (IL-18) in serum, were determined by ELISA. The expressions of mRNA and protein NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Gasdermin D (GSDMD), Cysteinyl aspartate specific proteinase1 (Caspase1), High mobility group box-1 protein (HMGB1) and Apoptosis-associated speck-like protein containing CARD (ASC) related to the cellular ferroptosis pathway were tested and analyzed by RT-PCR and WB respectively. RESULTS: PCPA significantly diminishes the sleep span of experimental animals by expediting the expenditure of 5-HT, consequently establishing an essentially direct SD model. The intervention of GHYSJ displays remarkable efficacy in mitigating insomnia symptoms, encompassing difficulties in initiating sleep and insufficient sleep duration. Likewise, it ameliorates memory function impairments induced by sleep deprivation, along with symptoms such as fatigue and depletion of vitality. GHYSJ exerts a protective influence on hippocampal neurons facilitated by inhibiting the down regulation of MAP2 and maintaining the equilibrium of neurotransmitters (5-HTP, 5-HT, GABA, and Glu). It diminishes the expression of intracellular pyroptosis-associated inflammatory factors (IL-1ß and IL-18) and curbs the activation of the NLRP3/Caspase1/GSDMD pyroptosis-related signaling pathways, thereby alleviating the damage caused by hippocampal neuronal pyroptosis.

Albumin-bilirubin score as a predictor of all-cause mortality in patients with hepatitis B virus infection: An analysis of National Health and Nutrition Examination Survey (NHANES) 1999-2018.

Objectives: The Albumin-Bilirubin (ALBI) score has been widely used to assess the prognosis in patients with cirrhosis and hepatocellular carcinoma. This study aimed to analyze the relationship between ALBI score and all-cause mortality in patients with hepatitis B virus (HBV) infection in general. Methods: Patients aged ≥ 18 years with previous or current HBV infection from the National Health and Nutrition Examination Survey (NHANES) in the United States between 1999 and 2018 were enrolled in this retrospective cohort study. Weight univariate and multivariate Cox regression models were used to assess the relationship between ALBI score and all-cause mortality. The area under the receiver operating characteristic curve (AUC) was utilized to assess the predictive effect of ALBI score for all-cause mortality. Results: A total of 3,666 patients were included, of whom 925 (23.53 %) patients died. Compared with ALBI score ≤ -2.6, HBV-infected patients with ALBI score > -2.6 [hazard ratio (HR) = 1.75; 95 % confidence interval (CI): 1.43-2.14] were corrected with a higher all-cause mortality risk after adjusting for confounders. Stratified analyses showed that higher ALBI score was related to a higher risk of all-cause mortality in different patients with HBV infection (All P < 0.05). Furthermore, the ALBI score had good predictive ability for 1-year (AUC = 0.816, 95 %CI: 0.754-0.878), 3-year (AUC = 0.808, 95 %CI: 0.775-0.841), 5-year (AUC = 0.809, 95 %CI: 0.783-0.835), and 10-year (AUC = 0.806, 95 %CI: 0.784-0.827) all-cause mortality. Conclusion: Higher ALBI score was related to a higher risk of all-cause mortality in patients with HBV infection, and the ALBI score showed a good predictive effect for short- and long-term all-cause mortality.