Pulmonary Fibrosis Ferret Model Demonstrates Sustained Fibrosis, Restrictive Physiology, and Aberrant Repair.

Rationale: The role of MUC5B mucin expression in IPF pathogenesis is unknown. Bleomycin-exposed rodent models do not exhibit sustained fibrosis or airway remodeling. Unlike mice, ferrets have human-like distribution of MUC5B expressing cell types and natively express the risk-conferring variant that induces high MUC5B expression in humans. We hypothesized that ferrets would consequently exhibit aberrant repair to propagate fibrosis similar to human IPF. Methods: Bleomycin (5U/kg) or saline-control was micro-sprayed intratracheally then wild-type ferrets were evaluated through 22 wks. Clinical phenotype was assessed with lung function. Fibrosis was assessed with µCT imaging and comparative histology with Ashcroft scoring. Airway remodeling was assessed with histology and quantitative immunofluorescence. Results: Bleomycin ferrets exhibited sustained restrictive physiology including decreased inspiratory capacity, decreased compliance, and shifted Pressure-Volume loops through 22 wks. Volumetric µCT analysis revealed increased opacification of the lung bleomycin-ferrets. Histology showed extensive fibrotic injury that matured over time and MUC5B-positive cystic structures in the distal lung suggestive of honeycombing. Bleomycin ferrets had increased proportion of small airways that were double-positive for CCSP and alpha-tubulin compared to controls, indicating an aberrant 'proximalization' repair phenotype. Notably, this aberrant repair was associated with extent of fibrotic injury at the airway level. Conclusions: Bleomycin-exposed ferrets exhibit sustained fibrosis through 22 wks and have pathologic features of IPF not found in rodents. Ferrets exhibited proximalization of the distal airways and other pathologic features characteristic of human IPF. MUC5B expression through native cell types may play a key role in promoting airway remodeling and lung injury in IPF.

Analysis of the therapeutic effect of synchronous integrated intensity modulated radiotherapy combined with chemotherapy in stage IIIc of cervical cancer.

Objective: To explore the Therapeutic effect of synchronous Integrated intensity modulated radiotherapy combined with chemotherapy in stage IIIc of Cervical Cancer. Methods: A total of 58 patients with stage IIIC cervical cancer (KPS ≥ 80) were analyzed in this study. They were admitted to our hospital between August 2017 and August 2022. Synchronous integrated boost intensity-modulated radiotherapy (SIB-IMRT) and sequential boost intensity-modulated radiotherapy (LCB-IMRT) were used to treat pelvic and/or para-aortic metastatic lymph nodes, with 30 cases in the SIB group and 28 cases in the LCB group. Comparison of short-term and long-term efficacy. Comparison of recurrence and metastasis rates, radiation dose to organs at risk and incidence of adverse drug reactions. Result: 30 patients were treated with simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT), and 28 patients were treated with sequential boost intensity-modulated radiotherapy (LCB-IMRT). At the completion of radiotherapy and 3 months after radiotherapy, there was no significant difference in clinical efficacy observed between the two treatment groups. The median overall survival (OS), progression-free survival (PFS), and disease-free survival (DMR) in the SIB-IMRT group were significantly higher compared to the LCB-IMRT group. The SIB-IMRT group demonstrated significantly lower rates compared to the LCB-IMRT group. Furthermore, within 3 years and 5 years, the rates of lymph node recurrence, cervical and vaginal local recurrence, and distant metastasis within the radiotherapy field were significantly lower in the SIB-IMRT group compared to the LCB-IMRT group. There were no significant differences observed between the two groups in terms of the maximum dose to the small intestine (Dmax), dose received by 2cc of the small intestine (D2cc), maximum dose to the rectum (Dmax), and dose received by 1cc of the bladder (D1cc). The incidence of bone marrow toxicity in the SIB-IMRT group was significantly lower compared to the LCB-IMRT group. Moreover, the occurrence of grade III and IV bone marrow toxicity was also significantly lower in the SIB-IMRT group compared to the LCB-IMRT group. Conclusion: The study has concluded that there is no significant differences in in terms of bladder associated adverse events and gastrointestinal toxicity in both Simultaneous Integrated Boost Intensity-Modulated Radiotherapy and Layered Conical Beam Intensity-Modulated Radiation Therapy.

A syrup containing L-arabinose and D-xylose appears superior to PEG-4000 as a bowel cleansing agent.

Adequate bowel cleansing is crucial for endoscopic diagnosis and treatment, and the recovery of gut microbiota after intestinal cleansing is also important. A hypertonic syrup predominantly comprising L-arabinose and D-xylose (20% xylo-oligosaccharides) can be extracted from the hemicellulose of corn husks and cobs. L-Arabinose and xylo-oligosaccharides have been reported to relieve constipation and improve the gut microbial environment. This study evaluated the bowel cleansing effect of the aforementioned syrup and its influence on the organism and intestinal microbiota after cleansing in comparison with polyethylene glycol-4000 (PEG-4000) in mice. Bowel cleansing was performed using syrup or PEG-4000 in C57BL/6J mice, and the effect of intestinal preparation and its influence on serum electrolytes and gut microbiota after bowel cleansing were evaluated. The volume of intestinal residual feces in the syrup group was significantly lower than that in the PEG-4000 group. Additionally, syrup disturbed serum electrolytes more mildly than PEG-4000. Alpha diversity in the gut microbiota was significantly higher in the syrup group than in the PEG-4000 group on the first day after bowel cleansing. However, no difference in beta diversity was observed between the two groups. Syrup increased the abundance of Bifidobacteria and Christensenella and decreased the abundance of Akkermansia in comparison with PEG-4000 on the first day after bowel cleansing. Thus, this syrup has potential clinical use as a bowel cleansing agent given the above effects, its benefits and safety, and better taste and acceptability.

Metabolomic analysis of rumen-protected branched-chain amino acids in primiparous dairy cows.

Introduction: Peripartal cows are susceptible to a negative energy balance due to inadequate nutrient intake and high energy requirements for lactation. Improving the energy metabolism of perinatal dairy cows is crucial in increasing production in dairy cows. Methods: In this study, we investigated the impact of rumen-protected branched-chain amino acid (RPBCAA) on the production performance, energy and lipid metabolism, oxidative stress, and immune function of primiparous dairy cows using metabolomics through a single-factor experiment. Twenty healthy primiparous Holstein cows were selected based on body condition scores and expected calving date, and were randomly divided into RPBCAA (n = 10) and control (n = 10) groups. The control group received a basal diet from calving until 21 d in milk, and the RPBCAA group received the basal diet and 44.6 g/d RPLeu, 25.14 g/d RPIle, and 25.43 g/d RPVal. Results: In comparison to the control group, the supplementation of RPBCAA had no significant effect on milk yield and milk composition of the dairy cows. Supplementation with RPBCAA significantly increased the concentrations of insulin, insulin growth factor 1, glucagon, and growth hormones, which are indicators of energy metabolism in postpartum cows. The very low density lipoprotein, fatty acid synthase, acetyl coenzyme A carboxylase, and hormone-sensitive lipase contents of the RPBCAA group were significantly greater than that of the control group; these metrics are related to lipid metabolism. In addition, RPBCAA supplementation significantly increased serum glutathione peroxidase and immunoglobulin G concentrations and decreased malondialdehyde concentrations. Liquid chromatography-mass spectrometry (LC-MS) analysis revealed 414 serum and 430 milk metabolic features. Supplementation with RPBCAA primarily increased concentrations of amino acid and lipid metabolism pathways and upregulated the abundance of serotonin, glutamine, and phosphatidylcholines. Discussion: In summary, adding RPBCAA to the daily ration can influence endocrine function and improve energy metabolism, regulate amino acid and lipid metabolism, mitigate oxidative stress and maintain immune function on primiparous cows in early lactation.

Research progress of prodrugs for the treatment of cerebral ischemia.

It is well-known that pharmacotherapy plays a pivotal role in the treatment and prevention of cerebral ischemia. Nevertheless, existing drugs, including numerous natural products, encounter various challenges when applied in cerebral ischemia treatment. These challenges comprise poor brain absorption due to low blood-brain barrier (BBB) permeability, limited water solubility, inadequate bioavailability, poor stability, and rapid metabolism. To address these issues, researchers have turned to prodrug strategies, aiming to mitigate or eliminate the adverse properties of parent drug molecules. In vivo metabolism or enzymatic reactions convert prodrugs into active parent drugs, thereby augmenting BBB permeability, improving bioavailability and stability, and reducing toxicity to normal tissues, ultimately aiming to enhance treatment efficacy and safety. This comprehensive review delves into multiple effective prodrug strategies, providing a detailed description of representative prodrugs developed over the past two decades. It underscores the potential of prodrug approaches to improve the therapeutic outcomes of currently available drugs for cerebral ischemia. The publication of this review serves to enrich current research progress on prodrug strategies for the treatment and prevention of cerebral ischemia. Furthermore, it seeks to offer valuable insights for pharmaceutical chemists in this field, offer guidance for the development of drugs for cerebral ischemia, and provide patients with safer and more effective drug treatment options.

Triterpenoids from the Leaves of Diospyros digyna and Their PTP1B Inhibitory Activity.

Six new 2α-hydroxy ursane triterpenoids, 3α-cis-p-coumaroyloxy-2α,19α-dihydroxy-12-ursen-28-oic acid (1), 3α-trans-p-coumaroyloxy-2α,19α-dihydroxy-12-ursen-28-oic acid (2), 3α-trans-p-coumaroyloxy-2α-hydroxy-12-ursen-28-oic acid (3), 3ß-trans-p-coumaroyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (4), 3ß-trans-feruloyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (5), and 3α-trans-feruloyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (6), along with eleven known triterpenoids (7-17), were isolated from the leaves of Diospyros digyna. Their chemical structures were elucidated by comprehensive analysis of UV, IR, HRESIMS, and NMR spectra. All the isolated compounds were evaluated for their PTP1B inhibitory activity. 3ß-O-trans-feruloyl-2α-hydroxy-urs-12-en-28-oic acid (13) showed the best inhibition activity with an IC50 value of 10.32 ± 1.21 µM. The molecular docking study found that the binding affinity of compound 13 for PTP1B was comparable to that of oleanolic acid (positive control).

Space-time cube uncovers spatiotemporal patterns of basin ecological quality and their relationship with water eutrophication.

Maintaining an optimal eco-environment is important for sustainable regional development. However, existing methods are inadequate for examining both spatial and temporal dimensions. Here, we propose a systematic procedure for spatiotemporal examination of the eco-environment using the space-time cube (STC) model and describe a preliminary investigation of the coupling relationships between basin ecological quality and water eutrophication in upstream of the Han River basin between 2000 and 2020. The STC model considers the temporal dimension as the third dimension in calculations. We first categorized the basin into three sub-watershed types: forest, cultivated land, and artificial surface. Subsequently, the ecological quality and driving factors were assessed and identified using the remote sensing ecological index (RSEI) and Geodetector method, respectively. The findings indicated that the forest basin and artificial surface basin had the highest and lowest ecological quality, respectively. The spatiotemporal cold spots of ecological quality during the past 20 years were mostly located in the vicinity of reservoirs, rivers, and artificial surface areas. Human activity, precipitation, and the percentage of cultivated land were other important driving factors in the artificial surface, forest, and cultivated land sub-watersheds, respectively, in addition to the dominant factors of elevation and temperature. The results also indicated that when the ecological quality degraded to a certain extent, water eutrophication was significantly coupled with the ecological quality of the catchments. The findings of this study are useful for ecological restoration and sustainable river basin development.

Electric Field Modeling in Personalizing Transcranial Magnetic Stimulation Interventions.

The modeling of transcranial magnetic stimulation (TMS)-induced electric fields (E-fields) is a versatile technique for evaluating and refining brain targeting and dosing strategies, while also providing insights into dose-response relationships in the brain. This review outlines the methodologies employed to derive E-field estimations, covering TMS physics, modeling assumptions, and aspects of subject-specific head tissue and coil modeling. We also summarize various numerical methods for solving the E-field and their suitability for various applications. Modeling methodologies have been optimized to efficiently execute numerous TMS simulations across diverse scalp coil configurations, facilitating the identification of optimal setups or rapid cortical E-field visualization for specific brain targets. These brain targets are extrapolated from neurophysiological measurements and neuroimaging, enabling precise and individualized E-field dosing in experimental and clinical applications. This necessitates the quantification of E-field estimates using metrics that enable the comparison of brain target engagement, functional localization, and TMS intensity adjustments across subjects. The integration of E-field modeling with empirical data has the potential to uncover pivotal insights into the aspects of E-fields responsible for stimulating and modulating brain function and states, enhancing behavioral task performance, and impacting the clinical outcomes of personalized TMS interventions.

Thyroid-stimulating hormone receptor (TSHR) as a target for imaging differentiated thyroid cancer.

BACKGROUND: Of the half a million cases of thyroid cancer diagnosed annually, 95% are differentiated thyroid cancers. Although clinical guidelines recommend surgical resection followed by radioactive iodine ablation, loss of sodium-iodine symporter expression causes up to 20% of differentiated thyroid cancers to become radioactive iodine refractory. For patients with radioactive iodine refractory disease, there is an urgent need for new diagnostic and therapeutic approaches. We evaluated the thyroid-stimulating hormone receptor as a potential target for imaging of differentiated thyroid cancer. METHODS: We immunostained tissue microarrays containing 52 Hurthle cell carcinomas to confirm thyroid-stimulating hormone receptor expression. We radiolabeled chelator deferoxamine conjugated to recombinant human thyroid-stimulating hormone analog superagonist TR1402 with 89Zr (t1/2 = 78.4 h, ß+ =22.7%) to produce [89Zr]Zr-TR1402. We performed in vitro uptake assays in high-thyroid-stimulating hormone receptor and low-thyroid-stimulating hormone receptor-expressing THJ529T and FTC133 thyroid cancer cell lines. We performed in vivo positron emission tomography/computed tomography and biodistribution studies in male athymic nude mice bearing thyroid-stimulating hormone receptor-positive THJ529T tumors. RESULTS: Immunohistochemical analysis revealed 62% of patients (27 primary and 5 recurrent) were thyroid-stimulating hormone receptor membranous immunostain positive. In vitro uptake of 1nM [89Zr]Zr-TR1402 was 38 ± 17% bound/mg in thyroid-stimulating hormone receptor-positive THJ529T thyroid cancer cell lines compared to 3.2 ± 0.5 in the low-expressing cell line (P < .01), with a similar difference seen in FTC133 cell lines (P < .0001). In vivo and biodistribution studies showed uptake of [89Zr]Zr-TR1402 in thyroid-stimulating hormone receptor-expressing tumors, with a mean percentage of injected dose/g of 1.9 ± 0.4 at 3 days post-injection. CONCLUSION: Our observation of thyroid-stimulating hormone receptor expression in tissue microarrays and [89Zr]Zr-TR1402 accumulation in thyroid-stimulating hormone receptor-positive thyroid cancer cells and tumors suggests thyroid-stimulating hormone receptor is a promising target for imaging of differentiated thyroid cancer.

Real-Time Computation of Brain E-Field for Enhanced Transcranial Magnetic Stimulation Neuronavigation and Optimization.

Transcranial Magnetic Stimulation (TMS) coil placement and pulse waveform current are often chosen to achieve a specified E-field dose on targeted brain regions. TMS neuronavigation could be improved by including real-time accurate distributions of the E-field dose on the cortex. We introduce a method and develop software for computing brain E-field distributions in real-time enabling easy integration into neuronavigation and with the same accuracy as 1st -order finite element method (FEM) solvers. Initially, a spanning basis set (< 400) of E-fields generated by white noise magnetic currents on a surface separating the head and permissible coil placements are orthogonalized to generate the modes. Subsequently, Reciprocity and Huygens' principles are utilized to compute fields induced by the modes on a surface separating the head and coil by FEM, which are used in conjunction with online (real-time) computed primary fields on the separating surface to evaluate the mode expansion. We conducted a comparative analysis of E-fields computed by FEM and in real-time for eight subjects, utilizing two head model types (SimNIBS's 'headreco' and 'mri2mesh' pipeline), three coil types (circular, double-cone, and Figure-8), and 1000 coil placements (48,000 simulations). The real-time computation for any coil placement is within 4 milliseconds (ms), for 400 modes, and requires less than 4 GB of memory on a GPU. Our solver is capable of computing E-fields within 4 ms, making it a practical approach for integrating E-field information into the neuronavigation systems without imposing a significant overhead on frame generation (20 and 50 frames per second within 50 and 20 ms, respectively).

Fast and accurate computational E-field dosimetry for group-level transcranial magnetic stimulation targeting.

Transcranial magnetic stimulation (TMS) is used to study brain function and treat mental health disorders. During TMS, a coil placed on the scalp induces an E-field in the brain that modulates its activity. TMS is known to stimulate regions that are exposed to a large E-field. Clinical TMS protocols prescribe a coil placement based on scalp landmarks. There are inter-individual variations in brain anatomy that result in variations in the TMS-induced E-field at the targeted region and its outcome. These variations across individuals could in principle be minimized by developing a large database of head subjects and determining scalp landmarks that maximize E-field at the targeted brain region while minimizing its variation using computational methods. However, this approach requires repeated execution of a computational method to determine the E-field induced in the brain for a large number of subjects and coil placements. We developed a probabilistic matrix decomposition-based approach for rapidly evaluating the E-field induced during TMS for a large number of coil placements due to a pre-defined coil model. Our approach can determine the E-field induced in over 1 Million coil placements in 9.5 h, in contrast, to over 5 years using a brute-force approach. After the initial set-up stage, the E-field can be predicted over the whole brain within 2-3 ms and to 2% accuracy. We tested our approach in over 200 subjects and achieved an error of <2% in most and <3.5% in all subjects. We will present several examples of bench-marking analysis for our tool in terms of accuracy and speed. Furthermore, we will show the methods' applicability for group-level optimization of coil placement for illustration purposes only. The software implementation link is provided in the appendix.

Effects of environmental factors on the river water quality on the Tibetan Plateau: a case study of the Xoirong River, China.

Climate, topography, and landscape patterns affect river water quality through processes that influence non-point source pollution. However, little is known about the response of the water quality of rivers on China's Tibetan Plateau to these environmental factors. Based on the water quality parameters data of the Xoirong River on the Tibetan Plateau in western China, the redundancy analysis and variation partitioning analysis were adopted to determine the main influencing factors affecting river water quality and their spatial scale effects. The major water pollutants were further analyzed using the partial least square-structural equation modeling (PLS-SEM). Another mountainous river with a similar latitude, the same stream order, and low anthropogenic disturbance in central China, the Jinshui River, was also selected for comparative discussion. The results indicated that the overall river water quality on the Tibetan Plateau was superior to that of the Jinshui River. At the catchment scale, the cumulative explanatory powers of the influencing factors of both rivers were greatest. Landscape composition and configuration were the determinant factors for the overall water quality of the two rivers, while the river on the Tibetan Plateau was also significantly affected by climatic and topographical factors. Regarding the main water quality issue, i.e., total nitrogen, agricultural production activities might be the main cause of the river on the Tibetan Plateau. This study unveiled that the river water quality on the Tibetan Plateau is sensitive to climate and topography through comparative studies.

Somatostatin Receptor Type 2 and Thyroid-Stimulating Hormone Receptor Expression in Oncocytic Thyroid Neoplasms: Implications for Prognosis and Treatment.

Somatostatin receptor type 2 (SSTR2) and thyroid-stimulating hormone receptor (TSHR) display variable expression in primary thyroid tumors and have been implicated as theranostic targets. This study was designed to explore the differential expression of SSTR2 and TSHR in oncocytic (Hurthle cell) carcinoma (OC) vs oncocytic adenoma (OA). We performed a retrospective review for oncocytic neoplasms treated at our institution from 2012 to 2019. Formalin-fixed paraffin-embedded tissue blocks were used for tissue microarray construction. Tissue microarray blocks were cut into 5-µm sections and stained with anti-SSTR2 and anti-TSHR antibodies. Immunostains were analyzed by 3 independent pathologists. χ2 and logistic regression analysis were used to analyze clinical and pathologic variables. Sixty-seven specimens were analyzed with 15 OA and 52 OC. The mean age was 57 years, 61.2% were women, and 70% were White. SSTR2 positivity was noted in 2 OA (13%) and 15 OC (28%; 10 primary, 4 recurrent, and 1 metastatic) (P = .22). TSHR positivity was noted in 11 OA (73%) and 32 OC (62%; 31 primary and 1 metastatic) (P = .40). Those who presented with or developed clinical recurrence/metastasis were more likely to be SSTR2-positive (50% vs 21%; P = .04) and TSHR-negative (64.3% vs 28.9%; P = .02) than primary OC patients. Widely invasive OC was more likely to be SSTR2-positive compared to all other OC subtypes (minimally invasive and angioinvasive) (P = .003). For all patients with OC, TSHR positivity was inversely correlated with SSTR2 positivity (odds ratio, 0.12; CI, 0.03-0.43; P = .006). This relationship was not seen in the patients with OA (odds ratio, 0.30; CI, 0.01-9.14; P = .440). Our results show that recurrent/metastatic OC was more likely to be SSTR2-positive and TSHR-negative than primary OC. Patients with OC displayed a significant inverse relationship between SSTR2 and TSHR expression that was not seen in patients with OA. This may be a key relationship that can be used to prognosticate and treat OCs.

Rapid Crystallization and Fluorescence of Poly(ethylene terephthalate) Using Graphene Quantum Dots as Nucleating Agents.

In this study, graphene quantum dots (GQDs) with a diameter of ~3 nm were successfully synthesized and incorporated into a poly(ethylene terephthalate) (PET) matrix to fabricate PET/GQDs nanocomposites. The impact of GQDs on the crystallization and thermal stability of the PET/GQDs nanocomposites was investigated. It was observed that the addition of only 0.5 wt% GQDs into the nanocomposites resulted in a significant increase in the crystallization temperature (peak temperature) of PET, from 194.3 °C to 206.0 °C during the cooling scan process. This suggested that an optimal concentration of GQDs could function as a nucleating agent and effectively enhance the crystallization temperature of PET. The isothermal crystallization method was employed to analyze the crystallization kinetics of the PET/GQDs nanocomposites, and the data showed that 0.5 wt% GQDs significantly accelerated the crystallization rate. Furthermore, the incorporation of GQDs into the PET matrix imparted photoluminescent properties to the resulting PET/GQDs nanocomposites. The PET crystals with GQDs as crystal nuclei and the crazes caused by defects played a vital role in isolating and suppressing the concentration quenching of GQDs. This effect facilitated the detection of defects in PET.

Novel Canthin-6-one Derivatives: Design, Synthesis, and Their Antiproliferative Activities via Inducing Apoptosis, Deoxyribonucleic Acid Damage, and Ferroptosis.

A series of novel canthin-6-one (CO) derivatives (8a-l) were designed and synthesized by introducing different amide side chains at the C-2 position, and their water solubility, antiproliferative activity, and preliminary mechanism were investigated. Most compounds displayed high cytotoxicity exhibiting low-micromolar IC50 values against four human cancer cell lines, especially HT29 cells. Meanwhile, the water solubility of active CO derivatives was significantly improved. Among these compounds, compound 8h with the N-methyl piperazine group exhibiting the highest antiproliferative capability with an IC50 value of 1.0 µM against HT29 cells, which was 8.6-fold lower than that of CO. Furthermore, 8h could upregulate the levels of reactive oxygen species, leading to mitochondrial damage. In addition, 8h could promote cell apoptosis and DNA damage by regulating the expression of apoptosis-associated proteins (Bcl-2 and cleaved-caspase 3) and the DNA damage-associated protein (H2AX). Most importantly, 8h also exerted ferroptosis by reducing the GSH level and GPX4 expression as well as increasing the lipid peroxidation level. Thus, the novel CO derivative 8h with N-methylpiperazine represents a promising anticancer candidate and warrants a more intensive study.

Boosting Oxygen Evolution Reaction of (Fe,Ni)OOH via Defect Engineering for Anion Exchange Membrane Water Electrolysis Under Industrial Conditions.

Developing non-precious catalysts with long-term catalytic durability and structural stability under industrial conditions is the key to practical alkaline anion exchange membrane (AEM) water electrolysis. Here, an energy-saving approach is proposed to synthesize defect-rich iron nickel oxyhydroxide for stability and efficiency toward the oxygen evolution reaction. Benefiting from in situ cation exchange, the nanosheet-nanoflake-structured catalyst is homogeneously embedded in, and tightly bonded to, its substrate, making it ultrastable at high current densities. Experimental and theoretical calculation results reveal that the introduction of Ni in FeOOH reduces the activation energy barrier for the catalytic reaction and that the purposely created oxygen defects not only ensure the exposure of active sites and maximize the effective catalyst surface but also modulate the local coordination environment and chemisorption properties of both Fe and Ni sites, thus lowering the energy barrier from *O to *OOH. Consequently, the optimized d-(Fe,Ni)OOH catalyst exhibits outstanding catalytic activity with long-term durability under both laboratory and industrial conditions. The large-area d-(Fe,Ni)OOH||NiMoN pair requires 1.795 V to reach a current density of 500 mA cm-2 at an absolute current of 12.5 A in an AEM electrolyzer for overall water electrolysis, showing great potential for industrial water electrolysis.

Serum metabolomics of hyperbilirubinemia and hyperuricemia in the Tibetan plateau has unique characteristics.

Few studies have provided data on the metabolomics characteristics of metabolic diseases such as hyperuricemia and hyperbilirubinemia in the Tibetan plateau. In the current study, we sought to investigate the serum metabolomics characteristics of hyperbilirubinemia and hyperuricemia in the Tibetan plateau, with the aim to provide a basis for further research on their pathogenesis, prevention, and treatment. The study participants were born in low-altitude areas below 1000 m and had no prior experience living in a high-altitude area before entering Golmud, Tibet (average elevation: 3000 m) and Yushu, Qinghai (average elevation: 4200 m). Thirty-four participants with hyperbilirubinemia (18 in Golmud and 16 in Yushu), 24 participants with hyperuricemia, and 22 healthy controls were enrolled. The serum samples of subjects were separated and then sent to a local tertiary hospital for biochemical examination. Serum widely targeted technology, based on the ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) platform, was used to detect serum metabolites and differential metabolites. Compared to the healthy controls, hyperbilirubinemia patients from Golmud showed 19 differential metabolites, hyperbilirubinemia patients from Yushu showed 12 differential metabolites, and hyperuricemia patients from Yushu showed 23 differential metabolites. Compared to the hyperbilirubinemia patients from Golmud that is at a low altitude, the Yushu groups had 33 different metabolites. Differential metabolites are primarily classified into amino acids and their derivatives, nucleotides and their derivatives, organic acids and their derivatives, and lipids/fatty acids. These are related to metabolic pathways such as caffeine metabolism, arachidonic acid metabolism, and tyrosine metabolism. Hyperbilirubinemia and hyperuricemia in the Tibetan plateau have unique serum metabolomics characteristics. Glycine derivatives and arachidonic acid and its derivatives were associated with plateau hyperbilirubinemia, and vanillic acid and pentadecafluorooctanoic acid were associated with plateau hyperuricemia.

Multilevel Assessment of Stent-Induced Inflammation in the Adjacent Vascular Tissue.

A recent U.S. Food and Drug Administration report presented the currently available scientific information related to biological response to metal implants. In this work, a multilevel approach was employed to assess the implant-induced and biocorrosion-related inflammation in the adjacent vascular tissue using a mouse stent implantation model. The implications of biocorrosion on peri-implant tissue were assessed at the macroscopic level via in vivo imaging and histomorphology. Elevated matrix metalloproteinase activity, colocalized with the site of implantation, and histological staining indicated that stent surface condition and implantation time affect the inflammatory response and subsequent formation and extent of neointima. Hematological measurements also demonstrated that accumulated metal particle contamination in blood samples from corroded-stetted mice causes a stronger immune response. At the cellular level, the stent-induced alterations in the nanostructure, cytoskeleton, and mechanical properties of circulating lymphocytes were investigated. It was found that cells from corroded-stented samples exhibited higher stiffness, in terms of Young's modulus values, compared to noncorroded and sham-stented samples. Nanomechanical modifications were also accompanied by cellular remodeling, through alterations in cell morphology and stress (F-actin) fiber characteristics. Our analysis indicates that surface wear and elevated metal particle contamination, prompted by corroded stents, may contribute to the inflammatory response and the multifactorial process of in-stent restenosis. The results also suggest that circulating lymphocytes could be a novel nanomechanical biomarker for peri-implant tissue inflammation and possibly the early stage of in-stent restenosis. Large-scale studies are warranted to further investigate these findings.

[A new dihydrochalcone from Humulus scandens].

To study the chemical constituents from the stems and leaves of Humulus scandens, this study isolated thirteen compounds by different chromatographic methods including silica gel column, ODS, Sephadex LH-20 and preparative HPLC. Based on comprehensive analysis, the chemical structures were elucidated and identified as citrunohin A(1), chrysosplenetin(2), casticin(3), neoechinulin A(4), ethyl 1H-indole-3-carboxylate(5), 3-hydroxyacetyl-indole(6),(1H-indol-3-yl) oxoacetamide(7), inonotusic acid(8), arteannuin B(9), xanthotoxol(10), α-tocopherol quinone(11), eicosanyl-trans-p-coumarate(12), and 9-oxo-(10E,12E)-octadecadienoic acid(13). Among them, compound 1 was a new dihydrochalcone, and the other compounds were obtained from H. scandens for the first time.

Comparison of toxic effects of 5 macrofungi against Drosophila melanogaster.

Traditional chemical pesticides pose potential threats to human health, the environment, and food safety, and there is an urgent need to develop botanical pesticides that are easily degradable, renewable, and environmentally compatible. This research serves to detect the lethal impacts of Amanita pantherina(DC.:Fr) Schrmm.(Agaricales, Amanitaceae, Amanita), Amanita virgineoides Bas (Agaricales, Amanitaceae, Amanita), Coprinus comatus (O.F.Müll.) Pers. (Agaricales, Psathyrellaceae, Coprinus), Pycnoporus cinnabarinus(Jacq.:Fr) Karst (Polyporales, Polyporaceae, Polyporus) and Phallus rubicundus (Bosc) Fr. (Phallales, Phallaceae, Phallus) on Drosophila melanogaster(Diptera, Drosophilidae, Drosophila), including their effects on lifespan, fecundity, offspring growth and developmental characteristics, antioxidant enzyme activity, peroxide content, and the gene transcription associated with signaling pathways and lifespan of D. melanogaster. The results demonstrated that they all produced lethal effects on D. melanogaster. Female flies were more sensitive to the addition of macrofungi to their diet and have a shorter survival time than male flies. The toxic activity of A. pantherina-supplemented diet was the strongest, so that the D. melanogaster in this group had no offspring. The macrofungal-supplemented diets were able to significantly reduce the activity of antioxidant enzymes, accumulate peroxidation products, up-regulatd the transcription of genes related to signaling pathways, inhibit the expression of longevity genes, reduce the lifespan and fertility of D. melanogaster. Consequently, we hypothetically suggest that medicinal C. comatus, P. cinnabarinus and P. rubicundus hold the potential to be developed into an environmentally friendly biopesticide for fly killing.