In this paper, the effect of hypoxia on the content of active ceramides in tissues was investigated for the first time, and the pharmacokinetic changes of ceramide C24:1 with hypoxia-protective effects were compared under both normoxic and hypoxic conditions. A UPLC-MS/MS method was developed to determine five ceramides in mouse tissues and plasma. The performance criteria for sensitivity, linearity, matrix effect, recovery, stability, precision, and accuracy were evaluated and found to be within the FDA-recommended guidelines. This method was successfully employed to quantify both endogenous and exogenous ceramides in tissues and plasma. The results revealed tissue-specific changes in endogenous ceramide levels under hypoxia and showed that hypoxia increased the systemic exposure and prolonged the retention of exogenous C24:1 while reducing its clearance. These findings support further investigation of ceramides as potential biomarkers or therapeutic targets for hypoxia-related diseases and provide important in vivo pharmacokinetic data for the development of novel neuroprotective drugs.

Phosphate-containing metabolites serve as critical regulators of energy homeostasis and signal transduction under hypoxic stress. However, their simultaneous quantification is technically challenging due to high polarity and non-specific adsorption. In this study, a sensitive UHPLC-MS/MS method was established for the simultaneous quantification of eight key phosphate metabolites, including adenosine triphosphate (ATP), phosphoenolpyruvate (PEP) and glucose-1-phosphate (P1G), in biological matrices. By compressing the analytical run time to <4 min per sample, this high-throughput platform demonstrated excellent linearity (r2 > 0.990) for all analytes. The method satisfied rigorous bioanalytical validation standards, exhibiting intra- and inter-day precision (RSD) of 2.2%-11.5% and accuracy of 87.0%-109.5%. Application of this method to in vitro and in vivo hypoxia models demonstrated its capability to capture distinct, context-dependent metabolic adaptations. Specifically, the platform differentiated the energetic trajectories of neuronal cells and cardiomyocytes under hypoxia and profiled metabolic shifts in mouse brain tissue. This study provides a reliable analytical platform for quantifying highly polar phosphate metabolites, offering a robust tool for monitoring metabolic pool dynamics under physiological and pathological stress.

Solar steam generation is of interest as a promising and sustainable technology in response to global water scarcity and energy scarcity. Despite great effort is continuously dedicated to exploiting powerful materials and excellent configurations, the synchronous modulation of electron behavior on both the solar absorption and the assembly of photothermal materials is still less well addressed for outstanding solar steam generation. Herein, the pi electrons of graphene are finely manipulated by varying the C/O (sp2/sp3) ratio, which further regulates the pi-conjugate network on the graphitic plane, and then tunes the 3D self-assembly. A combined experimental and theoretical investigation is firstly conducted on the effects of pi electron tuning on the solar absorption and photothermal conversion property of deoxidized graphene oxide (dGO), as well as the solar interfacial evaporation and salt recovery performance of dGO aerogels: 1) dGO with a high C/O ratio exhibits a sizable pi-conjugate network, reducing the band gap, leading to a mean solar absorbance as high as 97.6 %; 2) A dGO aerogel pi-pi self-stacked by dGO nanosheets with a C/O ratio of 4.63 affords the best balance between the water adsorption and heat insulation, yielding an extraordinary evaporation rate of 5.82 kg m- 2 h- 1 under one sun of irradiation; 3) A "U" shaped dGO aerogel is well designed to recover salt with a rate up to 0.374 kg m- 2 h- 1 as well as long-term evaporation performance. This work opens an effective route to design high-efficiency solar interfacial evaporators which especially has vital reference significance for carbonaceous and polymer-based photothermal materials.

Water/solvent solutions are commonly involved across various industries, particularly in pharmaceuticals. The separation of solutes from these liquids is a significant challenge for conventional nanofiltration (NF) membranes due to their inadequate resistance to organic solvents. Herein, a method for the thermal-stimulated crosslinking of polyetherimide (PEI) solvent-tolerant nanofiltration (STNF) membranes is proposed for molecular separation in binary water/solvent solutions. This technique enables facilely control over the support membrane's surface porosity, mean pore size, and crosslinking degree. The synthesized PEI-based thin film composite (TFC) membrane has shown to possess a uniform pore size distribution and an impressive water permeance of 12.9 L m(-2) h(-1) bar(-1) with MgSO4 rejection over 98.6 %. Benefiting from the cross-linked PEI support and the selective polyamide layer, the TFC STNF membrane exhibited excellent methyl orange rejections in water/solvent solutions with solvent content no more than 50 v/v%. Remarkably, its solvent resistance outperformed that of commercial NF membranes (Sepro NF2, Sepro NF6) and the permeance was one order of magnitude higher than that of the state-of-the-art STNF membranes. Moreover, the prepared TFC STNF membrane showed high rejections (>96 %) of four antibiotics in water/ethanol (50:50 v/v), demonstrating its significant potential for pharmaceutical separation processes.

The development of covalent organic frameworks (COFs) as bifunctional electrocatalysts for the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER), coupled with precise control over their active sites, is critical for advancing fuel cells and metal-air batteries. In this work, we present a series of three-dimensional (3D) COFs constructed from two strategically designed metal-porphyrin monomers. Among these, SUZ-101-Co stands out due to its high density of well-defined Co-N4 active sites, making it an outstanding bifunctional electrocatalyst. SUZ-101-Co exhibits an overpotential of only 240 mV at 10 mA cm-2 for the OER and achieves a half-wave potential of 0.78 V for the ORR, showcasing its superior catalytic performance. Comprehensive experimental analyses and theoretical simulations attribute this remarkable activity to the abundance and accessibility of Co-N4 sites. This study not only underscores the potential of 3D COFs in electrocatalysis but also introduces a novel approach for designing energy conversion materials.

Metal-organic framework (MOF) membranes exhibit great potential for molecular separations, but it remains a considerable challenge to achieve precise pore aperture regulation, typically requiring the synthesis of distinct MOF structures for each targeted separation. Herein, the first multivariate MOF (MTV-MOF) hollow fiber membranes with precision-tuned subnanometer channels have been fabricated by leveraging the heterogeneous spatial distribution of ligands, where reduced coordination energy barriers drive the formation of alternating narrow (local-path limited) and wide channels, simultaneously addressing the critical permeability-selectivity trade-off in membrane separations. The alternating narrow-wide channel architecture has been systematically investigated through combined density functional theory calculation, molecular dynamics simulation and mathematical modeling, with direct experimental validation provided by low-dose high-resolution scanning transmission electron microscopy and quantitative adsorption analysis. These MTV-MOF membranes demonstrated the ability to selectively separate aromatic hydrocarbons achieving highly selective separation while reduce the molecular transport barriers, offering significant potential for industrial separation processes.

Superhydrophobic and superoleophobic membranes offer great potential for energy-efficient oil-water separation, yet precise control of membrane wettability remains challenging. In this work, a pair of metal-organic framework (MOF)-coated mesh membranes were designed and successfully fabricated through a facile electrochemical fabrication process. By leveraging cathodically induced ligand assembly, this work achieved precise control over the surface chemistry, which resulted in a remarkable and reversible wettability transition between underwater superoleophobicity (θoil>150°) and superhydrophobicity (θwater>150°). The electrochemical deposition facilitates precise wettability inversion through ligand modification, providing a rapid, controllable, and substrate-adherent fabrication approach. Capitalizing on this, the T-shaped separation device was designed by integrating these two membranes with opposing wettability, achieving > 99 % purity in both light and heavy oil/water mixtures. This universal design demonstrates high-performance separation for oil-water mixtures across a wide density range, offering significant potential for complex industrial oily wastewater.

A single atom, with maximized atomic utilization and a tailored electronic structure, serves as a promising selective site for achieving ultrahigh selectivity in separation membranes. However, single-atom synthesis within membrane pores with the required chemical specificity for separation remains challenging. Here, we demonstrate single-atom gas separation using Ni single atoms confined in the 10-membered ring channels of (h0h)-oriented MFI zeolite membranes, which serve as intrinsic ultraselective sites for CO2. At an ultralow Ni loading of 0.037 wt %, the membrane achieves an ultrahigh H2/CO2 separation factor of 596, along with excellent H2 permeability of 1924 Barrer, while maintaining stable operation for over 200 h. This performance compares favorably with that of state-of-the-art membranes. Mechanistic studies reveal that hybridization of Ni-O orbitals preferentially interacts with CO2, in contrast to the weak physisorption of H2. This work establishes an atomic-level recognition mechanism in nanoporous architectures and offers new design principles for energy-critical gas separations.

The potential effects of Puerariae Lobatae Radix (Gegen in Chinese) water extract (GWE) on overactive bladder (OAB) were previously demonstrated through ex vivo examination of detrusor contraction. However, the mechanisms were not fully understood. The current aim was to investigate the therapeutic mechanisms of GWE against OAB in spontaneously hypertensive rats (SHR) with bladder ischemia. The therapeutic effect of GWE against OAB was evaluated by urodynamics. Hematoxylin & eosin (H&E) staining, Masson staining, and Doppler ultrasonic blood stream detector were utilized to observe bladder structures and local blood flow, respectively. To elucidate the mechanisms, an integrated omics approach was employed. The key proteins and metabolites were validated using Western Blotting and ELISA. A 3-week treatment of GWE demonstrated a significant improvement in urodynamic parameters. The results from Doppler detector, H&E staining, and Masson staining indicated that GWE improved vasodilation of bladder microvessels. Transcriptomic analysis revealed changes in genes such as Ptgfr and Ntsr1, which were involved in regulating intracellular Ca2+ concentration. Proteomic analysis suggested that the downregulation of epoxide hydrolase 2 (EPHX2), maintaining the balance of epoxyeicosatrienoic acids (EETs), was responsible for GWE-induced vasodilation. Metabolomic analysis further supported alterations in arachidonic acid (AA) metabolism. It is concluded that GWE treated OAB in SHR rats by improving bladder blood flow through the inhibition of EPHX2 and upregulation of EETs. This inhibition resulted in the improvement of bladder structure and the suppression of AA metabolism-mediated PTGES/PTGFR/PLCβ1/phospho-MLC signaling pathway.

Thin-film composite (TFC) reverse osmosis (RO) membranes, fabricated by interfacial polymerization, have achieved significant success in addressing the global water scarcity. Over the past three decades, the camphor sulfonic acid (CSA)/triethylamine (TEA) has been widely used in fabrication of TFC RO membranes. However, the mechanism of this unique formula remains elusive and contentious. In this work, for the first time, deciphering that introducing CSA/TEA into the aqueous phase has negligible impact on the selective polyamide (PA) layer but facilitate the aqueous solution impregnating of porous polysulfone (PSf) support. Specifically, the acidic CSA significantly hinders amine diffusion yet preserves the porosity of the PSf support during high-temperature curing. TEA is essential in modulating the pH changes and balancing the monomer diffusion rate that results from CSA. The COMSOL simulations have further elucidated that the presence of an aqueous solution within the porous support can mitigate the thermal expansion of the PSf, consequently inhibiting the shrinkage of surface pores. The TFC membrane demonstrated a substantial improvement in water permeance due to the preservation of its pore structure. The obtained TFC membrane demonstrated an exceptional NaCl rejection of 99.3 % and a high water flux of 76.8 L m-2h-1 (2000 ppm NaCl, 15.5 bar), exceeding that of the state-of-the-art TFC RO membranes. Moreover, the RO membrane manifested with long-term stability and good fouling resistance. The mechanistic insights have important implications to more efficient membrane-based desalination and water reuse, thereby reducing energy consumption and minimizing environmental carbon footprint.

Objective: Alpinia oxyphylla fructus without impurities and shells is called "Yi-Zhi-Ren" (YZR) in Chinese, and traditionally used to alleviate enuresis. The aim of this study was to investigate the effects and underlying mechanisms of YZR in the treatment of overactive bladder (OAB) in spontaneously hypertensive rats (SHR), a vascular disorder-related OAB model. Methods: A 3-week administration of YZR water extract (p.o.) was done, followed by urodynamics to measure bladder parameters. Changes in bladder structure were observed through H&E staining and Masson's staining. An integrated approach involving network pharmacology, transcriptomics and metabolomics was employed to elucidate the potential mechanisms of YZR, and the key proteins involved in the mechanisms were validated by Western blotting. Additionally, network pharmacology was used to predict the relationship between YZR's active components and validated proteins. Results: YZR treatment significantly improved the bladder storage parameters, tightened the detrusor layer, reduced inflammatory infiltration, and decreased collagen proportion in the SHR bladder. These results indicated that YZR water extract can alleviate OAB symptoms and improve bladder structure. Integrated analysis suggested that YZR may affect extracellular matrix-receptor interaction and calcium signaling pathway. Western blotting results further confirmed that the reduction in key proteins, such as TGF beta 1, p-SMAD3, collagen III, Gq and PLC beta 1, involved in collagen synthesis and calcium signaling pathways after YZR treatment. Network pharmacology predicted that sitosterol, chrysin, and nootkatone were potential components responsible for YZR's therapeutic effect on OAB. Conclusion: YZR's mechanisms of action in treating OAB involved the TGF beta 1-SMAD3 signaling pathway-related collagen synthesis and Gq-PLC beta 1 calcium signaling pathway, which are associated with detrusor contraction frequency and strength, respectively.

Objectives: Network pharmacology is essential for understanding the multi-target and multi-pathway therapeutic mechanisms of traditional Chinese medicine. This study aims to evaluate the influence of database quality on target identification and to explore the therapeutic potential of rhynchophylline (Rhy) in treating overactive bladder (OAB). Methods: An OAB dataset was constructed through extensive literature screening. Using this dataset, we applied network pharmacology to predict potential targets for Rhy, which is known for its therapeutic effects but lacks a well-defined target profile. Predicted targets were validated through in vitro experiments, including DARTS and CETSA. Results: Our analysis identified Rhy as a potential modulator of the M3 receptor and TRPM8 channel in the treatment of OAB. Validation experiments confirmed the interaction between Rhy and these targets. Additionally, the GeneCards database predicted other targets that are not directly linked to OAB, corroborated by the literature. Conclusions: We established a more accurate and comprehensive dataset of OAB targets, enhancing the reliability of target identification for drug treatments. This study underscores the importance of database quality in network pharmacology and contributes to the potential therapeutic strategies for OAB.

A MOF-derived nanoporous carbon (NPC MAF-4 -800) with multiple N-doped sites, considerable porous characteristics and inherent photothermal properties demonstrated a superior water-production rate under a relatively arid climate.

Background:: Chronic liver disease (CLD) will affect the enhancement of hepatic parenchyma and portal vein on abdominal-enhanced MRI. Objective:: To investigate the difference in liver parenchyma and portal vein enhancement in patients with CLD of different liver function grades between Gd- EOB-DTPA and Gd-DPTA in the portal venous phase (PVP). Methods:: This retrospective study included 218 patients with CLD who had undergone abdominal enhanced MRI from January 2019 to June 2020. Patients with various degrees of liver dysfunction were identified with Child-Turcotte-Pugh and albumin-bilirubin grade. Two readers measured the precontrast and PVP signal intensities of liver parenchyma, portal vein, spleen, and psoas muscle. Relative liver enhancement, liver-to-spleen contrast index, portal vein image contrast, and portal vein-to-liver contrast were calculated. Results:: The relative enhancement of liver parenchyma was significantly lower for the Gd-EOB-DTPA group in any degree of liver function than the Gd- DTPA group in the PVP. The Gd-EOB-DTPA group showed significantly lower portal vein-to-liver contrast in the overall study population, CTP class B, and ALBI grade 2 patients compared to the group of Gd-DTPA at PVP. No significant difference was noted in the portal vein image contrast between the two contrast agents, regardless of CTP and ALBI grading. Conclusion:: In CLD patients, Gd-EOB-DTPA yielded lower liver parenchymal enhancement and similar portal vein image contrast compared to Gd-DTPA in the PVP. Portal vein-to-liver contrast in the Gd-EOB-DTPA group was lower in the CTP class B and ALBI grade 2 subgroups compared to the Gd- DTPA group.

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Adaptation to hypoxia has attracted much public interest because of its clinical significance. However, hypoxic adaptation in the body is complicated and difficult to fully explore. To explore previously unknown conserved mechanisms and key proteins involved in hypoxic adaptation in different species, we first used a yeast model for mechanistic screening. Further multi-omics analyses in multiple species including yeast, zebrafish and mice revealed that glycerophospholipid metabolism was significantly involved in hypoxic adaptation with up-regulation of lysophospholipid acyltransferase (ALE1) in yeast, a key protein for the formation of dipalmitoyl phosphatidylcholine [DPPC (16:0/16:0)], which is a saturated phosphatidylcholine. Importantly, a mammalian homolog of ALE1, lysophosphatidylcholine acyltransferase 1 (LPCAT1), enhanced DPPC levels at the cell membrane and exhibited the same protective effect in mammalian cells under hypoxic conditions. DPPC supplementation effectively attenuated growth restriction, maintained cell membrane integrity and increased the expression of epidermal growth factor receptor under hypoxic conditions, but unsaturated phosphatidylcholine did not. In agreement with these findings, DPPC treatment could also repair hypoxic injury of intestinal mucosa in mice. Taken together, ALE1/LPCAT1-mediated DPPC formation, a key pathway of glycerophospholipid metabolism, is crucial for cell viability under hypoxic conditions. Moreover, we found that ALE1 was also involved in glycolysis to maintain sufficient survival conditions for yeast. The present study offers a novel approach to understanding lipid metabolism under hypoxia and provides new insights into treating hypoxia-related diseases.

Isoliquiritigenin (ISL) has excellent neuroprotective effects. However, its limitations, including poor solubility, low bioavailability, and low accumulation in the brain, restrict its clinical promotion. In this study, a novel type of ISL-loaded liposome (ISL-LP) modified with the brain-targeting polypeptide angiopep-2 was prepared to improve these properties. The zeta potential, morphology, particle size, encapsulation efficiency, drug loading, and in vitro release of ISL-LP were evaluated. The pharmacokinetics and tissue distribution of ISL and ISL-LP were also investigated. The results demonstrated that ISL-LP had an average particle size of 89.36 ± 5.04 nm, a polymer dispersity index of 0.17 ± 0.03, a zeta potential of −20.27 ± 2.18 mV, and an encapsulation efficiency of 75.04 ± 3.28%. The in vitro release experiments indicate that ISL-LP is a desirable sustained-release system. After intravenous administration, LPC-LP prolonged the circulation time of ISL in vivo and enhanced its relative brain uptake. In conclusion, ISL-LP could serve as a promising brain-targeting system for the treatment and prevention of central nervous system (CNS) disorders.

Choline acetyltransferase (ChAT)-positive neurons in neural stem cell (NSC) niches can evoke adult neurogenesis (AN) and restore impaired brain function after injury, such as acute ischemic stroke (AIS). However, the relevant mechanism by which ChAT+ neurons develop in NSC niches is poorly understood. Our RNA-seq analysis revealed that dimethylarginine dimethylaminohydrolase 1 (DDAH1), a hydrolase for asymmetric NG,NG-dimethylarginine (ADMA), regulated genes responsible for the synthesis and transportation of acetylcholine (ACh) (Chat, Slc5a7 and Slc18a3) after stroke insult. The dual-luciferase reporter assay further suggested that DDAH1 controlled the activity of ChAT, possibly through hypoxia-inducible factor 1α (HIF-1α). KC7F2, an inhibitor of HIF-1α, abolished DDAH1-induced ChAT expression and suppressed neurogenesis. As expected, DDAH1 was clinically elevated in the blood of AIS patients and was positively correlated with AIS severity. By comparing the results among Ddah1 general knockout (KO) mice, transgenic (TG) mice and wild-type (WT) mice, we discovered that DDAH1 upregulated the proliferation and neural differentiation of NSCs in the subgranular zone (SGZ) under ischemic insult. As a result, DDAH1 may promote cognitive and motor function recovery against stroke impairment, while these neuroprotective effects are dramatically suppressed by NSC conditional knockout of Ddah1 in mice.

Many studies have focused on the effects of small molecules, such as amino acids, on metabolism under hypoxia. Recent findings have indicated that phenylalanine levels were markedly elevated in adaptation to chronic hypoxia. This raises the possibility that phenylalanine treatment could markedly improve the hypoxic endurance. However, the importance of hypoxia-regulated phenylalanine is still unclear. This study investigates the role of phenylalanine in hypoxia adaptation using a hypoxic zebrafish model and multi-omics analysis. We found that phenylalanine-related metabolic pathways are significantly up-regulated under hypoxia, contributing to enhanced hypoxic endurance. Phenylalanine treatment reduced ROS levels, improved mitochondrial oxygen consumption rate (OCR), and extracellular acidification rate (ECAR) in hypoxic cells. Western blotting revealed increased phenylalanine uptake via L-type amino transporters (LAT1), activating the LKB1/AMPK signaling pathway. This activation up-regulated peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and the Bcl-2/Bax ratio, while down-regulating uncoupling protein 2 (UCP2), thereby improving mitochondrial function under hypoxia. This is the first comprehensive multi-omics analysis to demonstrate phenylalanine’s crucial role in hypoxia adaptation, providing insights for the development of anti-hypoxic drugs. Multi-omics analysis in hypoxic models indicated that the phenylalanine-related metabolic pathways strongly associated with hypoxia endurance. Phenylalanine uptake obviously alleviated the damage in hypoxic cells. Phenylalanine obviously activated LKB1/AMPK signaling pathway, so that enhanced the energy metabolism and cell survival.

Sojae semen germinatum (SSG) is derived from mature soybean seeds that have been germinated and dried, typically with sprouts measuring approximately 0.5 cm in length. SSG is traditionally known for its properties in clearing heat and moisture. Nevertheless, limited information was reported on the effects and mechanisms of SSG in alleviating urinary symptoms. This study employed urodynamic parameters to investigate the therapeutic effect of SSG water extract on overactive bladder (OAB) in the rat model with benign prostatic hyperplasia. Through a combination of transcriptomic and metabolomic analyses, the pathways and key proteins of the SSG treatment for OAB were identified and validated by ELISA and Western blotting. Furthermore, network pharmacology elucidated the roles of SSG's isoflavones acting on the target which was identified by above-mentioned multi-omics analysis. Our results indicate that SSG water extract significantly mitigated OAB by down-regulating the PGE2/EP1/PLCβ2/p-MLC signaling pathway. It was speculated that the active ingredient in the SSG on EP1 was genistein. This study provided valuable insights into the molecular mechanisms of SSG water extract, emphasizing the multi-target characteristics and critical pathways in improving OAB. Furthermore, this study contributes to the potential utilization of SSG as a functional food.