Preparation and properties of a metal-organic frameworks polymer material based on Sa-son seed gum capable of simultaneously absorbing liquid water and water vapor.

Atmospheric water harvesting (AWH) technology has attracted significant attention as an effective strategy to tackle the global shortage of freshwater resources. Work has focused on the use of hydrogel-based composite adsorbents in water harvesting and water conservation. The approaches adopted to make use of hygroscopic inorganic salts which subject to a "salting out" effect. In this study, we report the first use of modified UIO-66-NH2 as a functional steric cross-linker and Sa-son seed gum was used as polymeric substrate to construct super hygroscopic hydrogels by free radical copolymerization. The maximum water uptake on SMAGs (572 cm3·g-1) outperforms pure UIO-66-NH2 (317 cm3·g-1). Simultaneously, our first attempt to use it for anti-evaporation applications in an arid environment (Lanzhou, China) simulating sandy areas. The evaporation rate of the anti-evaporation material treated with 0.20 % super moisture-absorbent gels (SMAGs) decreased by 6.1 % over 64 h period under natural condition in Lanzhou, China. The prepared material can not only absorb liquid water but also water vapor, which can provide a new way for water collection and conservation technology. The design strategy of this material has wide applications ranging from atmospheric water harvesting materials to anti-evaporation technology.

Temperature dependence mechanism of high-temperature oxidation of transition metal silicide MoSi2.

Transition metal silicides represented by MoSi2 have excellent oxidation resistance and are widely used as high-temperature anti-oxidation coatings in hot end components of power equipment. However, the mechanism of temperature-dependent growth of MoSi2 oxidation products has not been revealed. Therefore, this study investigated the formation characteristics of oxide film and silicide-poor compound on MoSi2 at temperatures of 1000-1550℃ through high-temperature oxidation experiments, combined with microscopic Raman spectroscopy, SEM, and XRD characterizations. The result showed that MoSi2 underwent high-temperature selective oxidation reactions at 1000-1200℃, forming MoO2 and SiO2 oxide film on the substrate. As the oxidation temperature increased to 1550℃, after 100 hours of oxidation, along with the disappearance of MoO2 and the phase transformation of SiO2, a continuous Mo5Si3 layer with a thickness of approximately 47 µm was formed at the SiO2-MoSi2 interface. Thermodynamics and kinetic calculations further revealed the mechanism of temperature-dependent growth of oxidation products (MoO2 and Mo5Si3) during high-temperature oxidation process of MoSi2. As the temperature increased, the diffusion flux ratio of O and Si decreased, leading to a decrease in oxygen concentration at the interface and promoting the growth of the Mo5Si3 layer. Its thickness is an important indicator for evaluating the oxidation resistance of MoSi2 coatings during service. This study provides experimental and mechanistic insights into the temperature-dependent growth behavior of Mo5Si3 during the high-temperature oxidation of MoSi2 coating, and provides guidance for predicting the service life and improving the oxidation resistance of silicide coatings.

Single-Cell Transcriptome Sequencing Reveals Molecular Expression Differences and Marker Genes in Testes during the Sexual Maturation of Mongolian Horses.

This study aimed to investigate differences in testicular tissue morphology, gene expression, and marker genes between sexually immature (1-year-old) and sexually mature (10-year-old) Mongolian horses. The purposes of our research were to provide insights into the reproductive physiology of male Mongolian horses and to identify potential markers for sexual maturity. The methods we applied included the transcriptomic profiling of testicular cells using single-cell sequencing techniques. Our results revealed significant differences in tissue morphology and gene expression patterns between the two age groups. Specifically, 25 cell clusters and 10 cell types were identified, including spermatogonial and somatic cells. Differential gene expression analysis highlighted distinct patterns related to cellular infrastructure in sexually immature horses and spermatogenesis in sexually mature horses. Marker genes specific to each stage were also identified, including APOA1, AMH, TAC3, INHA, SPARC, and SOX9 for the sexually immature stage, and PRM1, PRM2, LOC100051500, PRSS37, HMGB4, and H1-9 for the sexually mature stage. These findings contribute to a deeper understanding of testicular development and spermatogenesis in Mongolian horses and have potential applications in equine reproductive biology and breeding programs. In conclusion, this study provides valuable insights into the molecular mechanisms underlying sexual maturity in Mongolian horses.

Preparation and epitope analysis of monoclonal antibodies against African swine fever virus DP96R protein.

BACKGROUND: Many proteins of African swine fever virus (ASFV, such as p72, p54, p30, CD2v, K205R) have been successfully expressed and characterized. However, there are few reports on the DP96R protein of ASFV, which is the virulence protein of ASFV and plays an important role in the process of host infection and invasion of ASFV. RESULTS: Firstly, the prokaryotic expression vector of DP96R gene was constructed, the prokaryotic system was used to induce the expression of DP96R protein, and monoclonal antibody was prepared by immunizing mice. Four monoclonal cells of DP96R protein were obtained by three ELISA screening and two sub-cloning; the titer of ascites antibody was up to 1:500,000, and the monoclonal antibody could specifically recognize DP96R protein. Finally, the subtypes of the four strains of monoclonal antibodies were identified and the minimum epitopes recognized by them were determined. CONCLUSION: Monoclonal antibody against ASFV DP96R protein was successfully prepared and identified, which lays a foundation for further exploration of the structure and function of DP96R protein and ASFV diagnostic technology.

GC/MS-based untargeted metabolomics reveals the differential metabolites for discriminating vintage of Chenxiang-type baijiu.

The "outstanding and unique aged aroma" of Chinese Chenxiang-type baijiu (CXB)-Daoguang 25 (DG25) mainly originates from a "extraordinary storage technology" of Mujiuhai (a wooden container), so it is mysterious and interesting. In this study, an untargeted GC/MS-based metabolomics was used to reveals the volatile differential metabolites for discriminating six different vintages of DG25 combing with chemometrics. A total of 100 volatile metabolites (including unknowns) were extracted and identified, including esters (41%), alcohols (10%) and acids (7%) so on. Finally, 33 differential metabolites were identified as aging-markers. Among them, 25 aging-markers showed a downtrend, including 17 esters such as ethyl acetate, ethyl hexanoate and ethyl palmitate so on. Moreover, it was interesting and to further study that furans showed a significant downtrend. Statistically speaking, ethyl benzoate played an important role in discriminating vintage of 1Y and 3Y, and the other 24 differential metabolites with downtrend discriminating the unstored (0Y-aged) DG25. Eight differential metabolites, such as ethyl octanoate, benzaldehyde, 3-methylbutanol and 1,1-diethoxyaccetal so on increased during aging of DG25, and they played a statistical role in discriminating the 5Y-, 10Y- and 20Y-aged DG25. This study provides a theoretical basis way for the formation mechanism of aging aroma for CXB.

Structural basis for substrate recognition by a S-adenosylhomocysteine hydrolase Lpg2021 from Legionella pneumophila.

S-Adenosyl-l-homocysteine hydrolase (SAHH) is a crucial enzyme that governs S-adenosyl methionine (SAM)-dependent methylation reactions within cells and regulates the intracellular concentration of SAH. Legionella pneumophila, the causative pathogen of Legionnaires' disease, encodes Lpg2021, which is the first identified dimeric SAHH in bacteria and is a promising target for drug development. Here, we report the structure of Lpg2021 in its ligand-free state and in complexes with adenine (ADE), adenosine (ADO), and 3-Deazaneplanocin A (DZNep). X-ray crystallography, isothermal titration calorimetry (ITC), and molecular docking were used to elucidate the binding mechanisms of Lpg2021 to its substrates and inhibitors. Virtual screening was performed to identify potential Lpg2021 inhibitors. This study contributes a novel perspective to the understanding of SAHH evolution and establishes a structural framework for designing specific inhibitors targeting pathogenic Legionella pneumophila SAHH.

Associations of Pain Sensitivity and Conditioned Pain Modulation with Physical Activity: Findings from the Multicenter Osteoarthritis Study (MOST).

OBJECTIVE: Individuals with chronic pain due to knee osteoarthritis (OA) are insufficiently physically active, and alterations of facilitatory and inhibitory nociceptive signaling are common in this population. Our objective was to examine the association of these alterations in nociceptive signaling with objective accelerometer-based measures of physical activity in a large observational cohort. DESIGN: We used data from the Multicenter Osteoarthritis Study (MOST). Measures of peripheral and central pain sensitivity included pressure pain threshold (PPT) at the knee and mechanical temporal summation (TS) at the wrist, respectively. The presence of descending pain inhibition was assessed by conditioned pain modulation (CPM). Physical activity was quantitatively assessed over 7-days using a lower back-worn activity monitor. Summary metrics included steps/day, activity intensity, and sedentary time. Linear regression analyses were used to evaluate the association of pain sensitivity and the presence of descending pain inhibition with physical activity measures. RESULTS: Data from 1,873 participants was analyzed (55.9% female, age = 62.8±10.0 years). People having greater peripheral and central sensitivity showed lower step counts. CPM was not significantly related to any of the physical activity measures, and none of the exposures were significantly related to sedentary time. CONCLUSIONS: In this cohort, greater peripheral and central sensitivity were associated with reduced levels of objectively-assessed daily step counts. Further research may investigate ways to modify or treat heightened pain sensitivity as a means to increase physical activity in older adults with knee OA.

A label free fluorescent aptamer sensor based on the combined action of Graphene oxide and SYBR Green I for the detection of Aflatoxin B1.

Here, based on the characteristics of Graphene oxide(GO) and SYBR Green I(SGI) dye, an enzyme-free and label-free fluorescent biosensor with signal amplification through DNA strand reaction is proposed for the detection of Aflatoxin B1(AFB1) in food safety. Firstly, without the addition of AFB1, the substrate in the system includes a double stranded Apt-S with a long sticky end and two hairpins H1 and H2. Although the complementary pairing of bases may exhibit fluorescence due to the insertion of SGI dyes, the use of GO, which is highly capable of adsorbing single stranded parts and quenching fluorescence, cleverly reduces the background fluorescence. Adding the target AFB1 triggers DNA inter chain reactions, generating a large amount of long double stranded DNA H1-H2, thereby generating strong fluorescence signals under the action of SGI. More importantly, logical theory verification and computer simulation were conducted before biological experiments, providing a theoretical basis for the implementation of the biosensor. After analysis, the fluorescence biosensor exhibits a good linear relationship with AFB1 concentration in the range of 5-50nM, with a detection limit of 0.76nM. It also has good specificity, anti-interference ability, and practical application ability, and has broad application prospects in the field of food safety.

Factors Affecting the Diagnostic Discordance Between Frozen and Permanent Sections in Mucinous Ovarian Tumors.

Purpose: To investigate the accuracy of intraoperative frozen section (FS) diagnosis for predicting the permanent section (PS) diagnosis of mucinous ovarian tumors and evaluate the factors affecting the diagnostic discordance. Patients and Methods: This retrospective cohort study was performed in Tianjin Medical University General Hospital. All women who underwent ovarian surgery with FS between January 2011 and December 2022 were identified, and those with a diagnosis of mucinous ovarian tumor (MOT) by FS or PS were reviewed. Clinical and pathologic data were extracted. Results: A total of 180 women were included, of which 141 (78.33%) had diagnostic concordance between FS and PS, yielding a sensitivity of 83.43% and a positive predictive value (PPV) of 92.76%. Under- and over-diagnosis occurred in 28 cases (15.56%) and 11 cases (6.11%). Tumor size > 13cm (OR 3.79, 95% CI 1.12-12.73) was an independent risk factor for under-diagnosis, and tumor size ≤ 13cm (OR 16.78, 95% CI 0.01-0.49), laparoscopic surgery (OR 0.14, 95% CI 0.02-0.92), the combination of other tumor components (including serous, Brenner tumor, and chocolate cyst; OR 7.00, 95% CI 1.19-41.12) were independently associated with over-diagnosis. The Kaplan-Meier survival curves and the Log rank test showed no significant difference between misdiagnosed and accurately diagnosed patients (all P > 0.05). Conclusion: Intraoperative frozen pathology of MOT is problematic for under- and over-diagnosis. The incorrect diagnosis of FS was related to determining the extent of surgery but had no impact on the patients' long-term recurrence and survival outcomes. In future clinical practice, surgeons need to obtain material accurately and enhance communication with pathologists during the operation to improve the accuracy of FS diagnosis.

Neurological disorders following the use of tumor necrosis factor-α inhibitors in inflammatory bowel disease patients: a real-world pharmacovigilance analysis.

BACKGROUND: Tumor necrosis factor-α inhibitors (TNFis) are used for the treatment of inflammatory bowel disease (IBD). The aim of this study was to evaluate the association between neurological adverse events (AEs) and TNFi use. METHODS: Data of TNFis indicated for IBD were collected from the Food and Drug Administration Adverse Event Reporting System (FAERS) from the marketed date to the second quarter of 2023. The reporting odds ratio (ROR) and a Bayesian confidence propagation neural network were used to identify signals. RESULTS: A total of 4,964 neurological AEs were reported in the IBD population. Infliximab had 3 signals, including demyelination [ROR (95% CI): 1.69 (1.33,2.15)], meningitis listeria [ROR (95% CI): 5.05 (3.52,7.25)], and optic neuritis [ROR (95% CI): 1.72 (1.3,2.26)]. The signals for adalimumab were gait disturbance [ROR (95% CI): 1.43 (1.32,1.56)] and muscular weakness [ROR (95% CI): 1.4 (1.27,1.55)]. A peripheral neuropathy signal was found for adalimumab [ROR (95% CI): 1.34 (1.18,1.53)] and certolizumab pegol [ROR (95% CI): 1.49 (1.07,2.08)]. However, there were no signals among neurological AEs for golimumab. CONCLUSION: Neurological signals were detected for TNFi use, indicating that the risk of neurological AEs requires additional attention in clinical use of TNFis.

Long-term combined blockade of CXCR4 and PD-L1 with in vivo reassembly for intensive tumor interference.

Negative immunoregulatory signal (PD-L1, CXCR4, et al.) and weak immunogenicity elicited immune system failing to detect and destroy cancerous cells. CXCR4 blockade promoted T cell tumor infiltration and increased tumor sensitivity to anti-PD-L1 therapy. Here, pH-responsive reassembled nanomaterials were constructed with anti-PD-L1 peptide and CXCR4 antagonists grafting (APAB), synergized with photothermal therapy for melanoma and breast tumor interference. The self-assembled APAB nanoparticles accumulated in the tumor and rapidly transformed into nanofibers in response to the acidic tumor microenvironment, leading to the exposure of grafted therapeutic agents. APAB enabling to reassemble around tumor cells and remained stable for over 96 h due to the aggregation induced retention (AIR) effect, led to long-term efficiently combined PD-L1 and CXCR4 blockade. Photothermal efficiency (ICG) induced immunogenic cell death (ICD) of tumor cells so as to effectively improve the immunogenicity. The combined therapy (ICG@APAB) could effectively inhibit the growth of primary tumor (∼83.52%) and distant tumor (∼76.24%) in melanoma-bearing mice, and significantly (p < 0.05) prolong the survival time over 42 days. The inhibition assay on tumor metastasis in 4 T1 model mice exhibited ICG@APAB almostly suppressed the occurrence of lung metastases and the expression levels of CD31, MMP-9 and VEGF in tumor decreased by 82.26%, 90.45% and 41.54%, respectively. The in vivo reassembly strategy will offer novel perspectives benefical future immunotherapies and push development of combined therapeutics into clinical settings.

Perceptions of Chinese women with a history of gestational diabetes regarding health behaviors and related factors: a directed qualitative content analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders during pregnancy and is associated with adverse outcomes in both mothers and their children. After delivery, women who experience GDM are also at higher risk of both subsequent GDM and type 2 diabetes mellitus (T2DM) than those who do not. Therefore, healthcare providers and public health practitioners need to develop targeted and effective interventions for GDM. In this study, we aimed to explore the perceptions regarding health behaviors and related factors during the inter-pregnancy period among Chinese women with a history of GDM through the lens of the theory of planned behavior (TPB). METHODS: Between December 2021 and September 2022, 16 pregnant Chinese women with a history of GDM were purposively recruited from a tertiary maternity hospital in Shanghai for face-to-face semi-structured interviews. They were asked questions regarding their health behaviors and related factors. The transcribed data were analyzed using a directed qualitative content analysis method based on the theory of TPB. RESULTS: The health-related behaviors of the women varied substantially. We identified five domains that influenced women's behaviors according to TPB constructs and based on the data collected: behavioral attitude (perceived benefits of healthy behaviors and the relationship between experience and attitude towards the oral glucose tolerance testing); subjective norms (influences of significant others and traditional cultural beliefs); perceived behavior control (knowledge of the disease, multiple-role conflict, the impact of COVID-19, an unfriendly external environment and difficulty adhering to healthy diets), incentive mechanisms (self-reward and external incentives); preferences of professional and institutional support (making full use of social media platform and providing continuous health management). CONCLUSIONS: The health-related behaviors of women with a history of GDM were found to be affected by multiple factors. Healthcare professionals are recommended to provide women with sufficient information regarding the disease and to take advantage of the power of the family and other social support networks to improve women's subjective norms and to promote the adoption of a healthy lifestyle.

A systematic review and meta-analysis of the morbidity of efficacy endpoints and bleeding events in elderly and young patients treated with the same dose rivaroxaban.

Rivaroxaban is a new direct oral anticoagulant, and the same dose is recommended for older and young patients. However, recent real-world studies show that older patients may need dose adjustment to prevent major bleeding. At present, the evidence for dose adjustment in older patients is extremely limited with only a few reports on older atrial fibrillation patients. The aim of this study was to review the morbidity data of adverse events and bleeding events across all indications for older and young patients treated with the same dose of rivaroxaban to provide some support for dosage adjustment in older patients. The PubMed, EMBASE, ClinicalTrials, Cochrane and Web of Science databases were searched for randomized controlled trials (RCTs) published between January 1, 2005, and October 10, 2023. The primary outcomes were the morbidity of bleeding events and efficacy-related adverse events. Summary estimates were calculated using a random effects model. Eighteen RCTs were included in the qualitative analysis. The overall morbidity of primary efficacy endpoints was higher in older patients compared to the young patients (3.37% vs. 2.60%, χ2 = 5.24, p = 0.022). Similarly, a higher morbidity of bleeding was observed in older patients compared to the young patients (4.42% vs. 6.03%, χ2 = 13.22, p < 0.001). Among all indications, deep vein thrombosis, pulmonary embolism and atrial fibrillation were associated with the highest incidence of bleeding in older patients, suggesting that these patients may be most need dose adjustment. Patients older than 75 years may require extra attention to prevent bleeding. The same dose of rivaroxaban resulted in higher bleeding morbidity and morbidity of efficacy-related adverse events in older patients compared to the young patients. An individualized dose adjustment may be preferred for older patients rather than a fixed dose that fits all.

Icariside II modulates pulmonary fibrosis via PI3K/Akt/ß-catenin pathway inhibition of M2 macrophage program.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a debilitating interstitial lung disorder characterized by its limited therapeutic interventions. Macrophages, particularly the alternatively activated macrophages (M2 subtype), have been acknowledged for their substantial involvement in the development of pulmonary fibrosis. Hence, targeting macrophages emerges as a plausible therapeutic avenue for IPF. Icariside II (ISE II) is a natural flavonoid glycoside molecule known for its excellent anti-tumor and anti-fibrotic activities. Nevertheless, the impact of ISE II on pulmonary fibrosis and the intricate mechanisms through which it operates have yet to be elucidated. OBJECTIVE: To scrutinize the impact of ISE II on the regulation of M2 macrophage polarization and its inhibitory effect on pulmonary fibrosis, as well as to delve deeper into the underlying mechanisms of its actions. METHODS: The effect of ISE II on proliferation and apoptosis in RAW264.7 cells was assessed through the use of EdU-488 labeling and the Annexin V/PI assay. Flow cytometry, western blot, and qPCR were employed to detect markers associated with the M2 polarization phenotype. The anti-fibrotic effects of ISE II in NIH-3T3 cells were investigated in a co-culture with M2 macrophages. Si-Ctnnb1 and pcDNA3.1(+)-Ctnnb1 plasmid were used to investigate the mechanism of targeted intervention. The murine model of pulmonary fibrosis was induced by intratracheal administration of bleomycin (BLM). Pulmonary function, histopathological manifestations, lung M2 macrophage infiltration, and markers associated with pulmonary fibrosis were evaluated. Furthermore, in vivo transcriptomics analysis was employed to elucidate differentially regulated genes in lung tissues. Immunofluorescence, western blot, and immunohistochemistry were conducted for corresponding validation. RESULTS: Our investigation demonstrated that ISE II effectively inhibited the proliferation of RAW264.7 cells and mitigated the pro-fibrotic characteristics of M2 macrophages, exemplified by the downregulation of CD206, Arg-1, and YM-1, Fizz1, through the inhibition of the PI3K/Akt/ß-catenin signaling pathway. This impact led to the amelioration of myofibroblast activation and the suppression of nuclear translocation of ß-catenin of NIH-3T3 cells in a co-culture. Consequently, it resulted in decreased collagen deposition, reduced infiltration of profibrotic macrophages, and a concurrent restoration of pulmonary function in mice IPF models. Furthermore, our RNA sequencing results showed that ISE II could suppress the expression of genes related to M2 polarization, primarily by inhibiting the PI3K/Akt and ß-catenin signaling pathway. In essence, our findings suggest that ISE II holds potential as an anti-fibrotic agent by orchestrating macrophage polarization. This may have significant implications in clinical practice. CONCLUSION: This study has provided evidence that ISE II exerts a significant anti-fibrotic effect by inhibiting macrophage M2 polarization through the suppression of the PI3K/Akt/ß-catenin signaling pathway. These findings underscore the potential of ISE II as a promising candidate for the development of anti-fibrotic pharmaceuticals in the future.

Oridonin exerts anticonvulsant profile and neuroprotective activity in epileptic mice by inhibiting NLRP3-mediated pyroptosis.

BACKGROUND: Epilepsy is a chronic disabling disease poorly controlled by available antiseizure medications. Oridonin, a bioactive alkaloid with anti-inflammatory properties and neuroprotective effects, can inhibit the increased excitability of neurons caused by glutamate accumulation at the cellular level. However, whether oridonin affects neuronal excitability and whether it has antiepileptic potential has not been reported in animal models or clinical studies. METHOD: Pentylenetetrazol was injected into mice to create a model of chronic epilepsy. Seizure severity was assessed using the Racine scale, and the duration and latency of seizures were observed. Abnormal neuronal discharge was detected using electroencephalography, and neuronal excitability was assessed using calcium imaging. Damage to hippocampal neurons was evaluated using Hematoxylin-Eosin and Nissl staining. The expression of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and other pyroptosis-related proteins was determined using western blotting and immunofluorescence. A neuronal pyroptosis model was established using the supernatant of BV2 cells treated with lipopolysaccharide and adenosine triphosphate to stimulate hippocampal neurons. RESULTS: Oridonin (1 and 5 mg/kg) reduced neuronal damage, increased the latency of seizures, and shortened the duration of fully kindled seizures in chronic epilepsy model mice. Oridonin decreased abnormal discharge during epileptic episodes and suppressed increased neuronal excitability. In vitro experiments showed that oridonin alleviated pyroptosis in hippocampal HT22 neurons. CONCLUSION: Oridonin exerts neuroprotective effects by inhibiting pyroptosis through the NLRP3/caspase-1 pathway in chronic epilepsy model mice. It also reduces pyroptosis in hippocampal neurons in vitro, suggesting its potential as a therapy for epilepsy.

Impact of low-level exposure to antibiotics on bile acid homeostasis in adults: Implication for human safety thresholds.

Bile acid homeostasis is critical to human health. Low-level exposure to antibiotics has been suggested to potentially disrupt bile acid homeostasis by affecting gut microbiota, but relevant data are still lacking in humans, especially for the level below human safety threshold. We conducted a cross-sectional study in 4247 Chinese adults by measuring 34 parent antibiotics and their metabolites from six common categories (i.e., tetracyclines, qinolones, macrolides, sulfonamides, phenicols, and lincosamides) and ten representative bile acids in fasting morning urine using liquid chromatography coupled to mass spectrometry. Daily exposure dose of antibiotics was estimated from urinary concentrations of parent antibiotics and their metabolites. Urinary bile acids and their ratios were used to reflect bile acid homeostasis. The estimated daily exposure doses (EDED) of five antibiotic categories with a high detection frequency (i.e., tetracyclines, qinolones, macrolides, sulfonamides, and phenicols) were significantly associated with urinary concentrations of bile acids and decreased bile acid ratios in all adults and the subset of 3898 adults with a cumulative ratio of antibiotic EDED to human safety threshold of less than one. Compared to a negative detection of antibiotics, the lowest EDED quartiles of five antibiotic categories and four individual antibiotics with a high detection frequency (i.e., ciprofloxacin, ofloxacin, trimethoprim, and florfenicol) in the adults with a positive detection of antibiotics had a decrease of bile acid ratio between 6.6% and 76.6%. Except for macrolides (1.2×102 ng/kg/day), the medians of the lowest EDED quartile of antibiotic categories and individual antibiotics ranged from 0.32 ng/kg/day to 10 ng/kg/day, which were well below human safety thresholds. These results suggested that low-level antibiotic exposure could disrupt bile acid homeostasis in adults and existing human safety thresholds may be inadequate in safeguarding against the potential adverse health effects of low-level exposure to antibiotics.

Highly sensitive and accurate measurement of underivatized phosphoenolpyruvate in plasma and serum via EDTA-facilitated hydrophilic interaction liquid chromatography-tandem mass spectrometry.

Phosphoenolpyruvate (PEP) is an essential intermediate metabolite that is involved in various vital biochemical reactions. However, achieving the direct and accurate quantification of PEP in plasma or serum poses a significant challenge owing to its strong polarity and metal affinity. In this study, a sensitive method for the direct determination of PEP in plasma and serum based on ethylenediaminetetraacetic acid (EDTA)-facilitated hydrophilic interaction liquid chromatography-tandem mass spectrometry was developed. Superior chromatographic retention and peak shapes were achieved using a zwitterionic stationary-phase HILIC column with a metal-inert inner surface. Efficient dechelation of PEP-metal complexes in serum/plasma samples was achieved through the introduction of EDTA, resulting in a significant enhancement of the PEP signal. A PEP isotopically labelled standard was employed as a surrogate analyte for the determination of endogenous PEP, and validation assessments proved the sensitivity, selectivity, and reproducibility of this method. The method was applied to the comparative quantification of PEP in plasma and serum samples from mice and rats, as well as in HepG2 cells, HEK293T cells, and erythrocytes; the results confirmed its applicability in PEP-related biomedical research. The developed method can quantify PEP in diverse biological matrices, providing a feasible opportunity to investigate the role of PEP in relevant biomedical research.

AMPK-a key factor in crosstalk between tumor cell energy metabolism and immune microenvironment?

Immunotherapy has now garnered significant attention as an essential component in cancer therapy during this new era. However, due to immune tolerance, immunosuppressive environment, tumor heterogeneity, immune escape, and other factors, the efficacy of tumor immunotherapy has been limited with its application to very small population size. Energy metabolism not only affects tumor progression but also plays a crucial role in immune escape. Tumor cells are more metabolically active and need more energy and nutrients to maintain their growth, which causes the surrounding immune cells to lack glucose, oxygen, and other nutrients, with the result of decreased immune cell activity and increased immunosuppressive cells. On the other hand, immune cells need to utilize multiple metabolic pathways, for instance, cellular respiration, and oxidative phosphorylation pathways to maintain their activity and normal function. Studies have shown that there is a significant difference in the energy expenditure of immune cells in the resting and activated states. Notably, competitive uptake of glucose is the main cause of impaired T cell function. Conversely, glutamine competition often affects the activation of most immune cells and the transformation of CD4+T cells into inflammatory subtypes. Excessive metabolite lactate often impairs the function of NK cells. Furthermore, the metabolite PGE2 also often inhibits the immune response by inhibiting Th1 differentiation, B cell function, and T cell activation. Additionally, the transformation of tumor-suppressive M1 macrophages into cancer-promoting M2 macrophages is influenced by energy metabolism. Therefore, energy metabolism is a vital factor and component involved in the reconstruction of the tumor immune microenvironment. Noteworthy and vital is that not only does the metabolic program of tumor cells affect the antigen presentation and recognition of immune cells, but also the metabolic program of immune cells affects their own functions, ultimately leading to changes in tumor immune function. Metabolic intervention can not only improve the response of immune cells to tumors, but also increase the immunogenicity of tumors, thereby expanding the population who benefit from immunotherapy. Consequently, identifying metabolic crosstalk molecules that link tumor energy metabolism and immune microenvironment would be a promising anti-tumor immune strategy. AMPK (AMP-activated protein kinase) is a ubiquitous serine/threonine kinase in eukaryotes, serving as the central regulator of metabolic pathways. The sequential activation of AMPK and its associated signaling cascades profoundly impacts the dynamic alterations in tumor cell bioenergetics. By modulating energy metabolism and inflammatory responses, AMPK exerts significant influence on tumor cell development, while also playing a pivotal role in tumor immunotherapy by regulating immune cell activity and function. Furthermore, AMPK-mediated inflammatory response facilitates the recruitment of immune cells to the tumor microenvironment (TIME), thereby impeding tumorigenesis, progression, and metastasis. AMPK, as the link between cell energy homeostasis, tumor bioenergetics, and anti-tumor immunity, will have a significant impact on the treatment and management of oncology patients. That being summarized, the main objective of this review is to pinpoint the efficacy of tumor immunotherapy by regulating the energy metabolism of the tumor immune microenvironment and to provide guidance for the development of new immunotherapy strategies.

Anion-Coordination Foldamer-Based Polymer Network: from Molecular Spring to Elastomer.

Foldamer is a scaled-down version of coil spring, which can absorb and release energy by conformational change. Here, polymer networks with high-density of molecular springs were developed by employing anion-coordination-based foldamers as the monomer. The coiling of the foldamer is controlled by oligourea ligands coordinating to chloride ions; subsequently, the folding and unfolding of foldamer conformations endow the polymer network with excellent energy dissipation and toughness. The mechanical performance of the corresponding polymer network shows a dramatic increase from P-L2UCl (non-folding), P-L4UCl (a full turn) to P-L6UCl (1.5 turns), in terms of strength (2.62 MPa; 14.26 Mpa; 22.93 Mpa), elongation at break (70%; 325%; 352%), Young's modulus (2.69 MPa; 63.61 Mpa; 141.50 Mpa), and toughness (1.12 MJ/m3; 21.39 MJ/m3; 49.62 MJ/m3), respectively, which are also better than those without anion centers and the non-foldamer based counterparts. Moreover, P-L6UCl shows enhanced strength and toughness than most of the molecular-spring based polymer networks.Moreover, P-L6UCl shows enhanced strength and toughness than most of the molecular-spring based polymer networks. Thus, an effective strategy for designing high-performance anion-coordination-based materials is presented in this study.