Background: The disruption of intracranial fluid dynamics due to large unruptured cerebral arteriovenous malformation (AVM) commonly triggers a domino effect within the central nervous system. This phenomenon is frequently overlooked in prior clinic and may lead to catastrophic misdiagnoses. Our team has documented the world's first case of so-called AVM Pentalogy (AVMP) induced by a AVM. Clinical presentation and result: A 30-year-old female was first seen 9 years ago with an occasional fainting, at which time a huge unruptured AVM was discovered. Subsequently, due to progressive symptoms, she sought consultations from several prestigious neurosurgical departments in China, where all consulting neurosurgeons opted for conservation treatment due to perceived surgical risks. During the follow-up period, the patient gradually presented with hydrocephalus, empty sella, secondary Chiari malformation, syringomyelia, and scoliosis (we called as AVMP). When treated in our department, she already displayed numerous symptoms, including severe intracranial hypertension. Our team deduced that the hydrocephalus was the primary driver of her AVMP symptoms, representing the most favorable risk profile for intervention. As expected, a ventriculoperitoneal shunt successfully mitigated all symptoms of AVMP at 21-months post-surgical review. Conclusion: During the monitoring of unruptured AVM, it is crucial to remain vigilant for the development or progression of AVMP. When any component of AVMP is identified, thorough etiological studies and analysis of cascade reactions are imperative to avert misdiagnosis. When direct AVM intervention is not viable, strategically addressing hydrocephalus as part of the AVMP may serve as the critical therapeutic focus.
Propane dehydrogenation (PDH) serves as a pivotal intentional technique to produce propylene. The stability of PDH catalysts is generally restricted by the readsorption of propylene which can subsequently undergo side reactions for coke formation. Herein, we demonstrate an ultrastable PDH catalyst by encapsulating PtIn clusters within silicalite-1 which serves as an efficient promoter for olefin desorption. The mean lifetime of PtIn@S-1 (S-1, silicalite-1) was calculated as 37317 h with high propylene selectivity of >97% at 580 °C with a weight hourly space velocity (WHSV) of 4.7 h-1. With an ultrahigh WHSV of 1128 h-1, which pushed the catalyst away from the equilibrium conversion to 13.3%, PtIn@S-1 substantially outperformed other reported PDH catalysts in terms of mean lifetime (32058 h), reaction rates (3.42 molpropylene gcat-1 h-1 and 341.90 molpropylene gPt-1 h-1), and total turnover number (14387.30 kgpropylene gcat-1). The developed catalyst is likely to lead the way to scalable PDH applications.
Jasmonic acid (JA) and gibberellin (GA) coordinately regulate plant developmental programs and environmental cue responses. However, the fine regulatory network of the cross-interaction between JA and GA remains largely elusive. In this study, we demonstrate that MdNAC72 together with MdABI5 positively regulates anthocyanin biosynthesis through an exquisite MdNAC72-MdABI5-MdbHLH3 transcriptional cascade in apple. MdNAC72 interacts with MdABI5 to promote the transcriptional activation of MdABI5 on its target gene MdbHLH3 and directly activates the transcription of MdABI5. The MdNAC72-MdABI5 module regulates the integration of JA and GA signals in anthocyanin biosynthesis by combining with JA repressor MdJAZ2 and GA repressor MdRGL2a. MdJAZ2 disrupts the MdNAC72-MdABI5 interaction and attenuates the transcriptional activation of MdABI5 by MdNAC72. MdRGL2a sequesters MdJAZ2 from the MdJAZ2-MdNAC72 protein complex, leading to the release of MdNAC72. The E3 ubiquitin ligase MdSINA2 is responsive to JA and GA signals and promotes ubiquitination-dependent degradation of MdNAC72. The MdNAC72-MdABI5 interface fine-regulates the integration of JA and GA signals at the transcriptional and posttranslational levels by combining MdJAZ2, MdRGL2a, and MdSINA2. In summary, our findings elucidate the fine regulatory network connecting JA and GA signals with MdNAC72-MdABI5 as the core in apple.
Lithium cobalt oxide (LiCoO2) is considered as one of the promising building blocks that can be used to fabricate all-solid-state thin film batteries (TFBs) because of its easy accessibility, high working voltage, and high energy density. However, the slow interfacial dynamics between LiCoO2 and LiPON in these TFBs results in undesirable side reactions and severe degradation of cycling and rate performance. Herein, amorphous vanadium pentoxide (V2O5) film was employed as the interfacial layer of a cathode-electrolyte solid-solid interface to fabricate all-solid-state TFBs using a magnetron sputtering method. The V2O5 thin film layer assisted in the construction of an ion transport network at the cathode/electrolyte interface, thus reducing the electrochemical redox polarization potential. The V2O5 interfacial layer also effectively suppressed the side reactions between LiCoO2 and LiPON. In addition, the interfacial resistance of TFBs was significantly decreased by optimizing the thickness of the interfacial modification layer. Compared to TFBs without the V2O5 layer, TFBs based on LiCoO2/V2O5/LiPON/Li with a 5 nm thin V2O5 interface modification layer exhibited a much smaller charge transfer impedance (Rct) value, significantly improved discharge specific capacity, and superior cycling and rate performance. The discharge capacity remained at 75.6% of its initial value after 1000 cycles at a current density of 100 µA cm-2. This was mainly attributed to the enhanced lithium ion transport kinetics and the suppression of severe side reactions at the cathode-electrolyte interface in TFBs based on LiCoO2/V2O5/LiPON/Li with a 5 nm V2O5 thin layer.
The individual toxicity of sodium fluoride (NaF) and microplastics (MPs) has been extensively documented. Owing to their high specific surface area, widespread presence and durability, MPs can adsorb a broad spectrum of environmental contaminants into the organism. However, the combined toxicity of NaF and MPs has not been investigated. This study aimed to assess the effects of combined exposure to NaF and MPs on the function of testicular Sertoli cells (SCs) in male mice, and to investigate the underlying molecular mechanisms. The study revealed that combined exposure to NaF and MPs resulted in a decrease in the negative surface charge of MPs, along with an increase in the number of MPs entering the SCs. Through in vivo observation of the testicular pathological structure, spermatogenesis, and cell apoptosis in 180-day-old male mice, we discovered that combined exposure to NaF (80â¯mg/L) and MPs (10â¯mg/L) heightened reproductive toxicity compared to the individual exposure groups. This was evidenced by testicular structural defects, impaired spermatogenesis, and increased testicular cell apoptosis. Our in vitro studies showed that NaF (21⯵g/mL) and MPs (100⯵g/mL) synergistically induced SCs apoptosis and ferroptosis, leading to a reduction in SCs number and dysfunction. This ultimately resulted in structural and functional damage to the testes. Our findings demonstrate, for the first time, the synergistic effects of NaF and MPs on reproductive toxicity in mammals. These insights may provide valuable contributions to co-toxicity studies involving MPs and other environmental pollutants.
INTRODUCTION: Cisplatin (DDP) is the commonest chemo drug in lung adenocarcinoma (LUAD) treatment, and DDP resistance is a significant barrier to therapeutic therapy. This study attempted to elucidate the impact of PDK1 on DDP resistance in LUAD and its mechanism. METHODS: Bioinformatics analysis was used to determine the expression and enriched pathways of PDK1 in LUAD tissue. Subsequently, E2F8, the upstream transcription factor of PDK1 was predicted, and the binding relationship between the two was analyzed using dual-luciferase and ChIP experiments. PDK1 and E2F8 levels in LUAD tissues and cells were detected via qPCR. Cell viability, proliferation, and apoptosis levels were assayed by CCK-8, EdU, and flow cytometry experiments, respectively. Comet assay was used to assess DNA damage, and immunofluorescence was used to assess the expression of γ-H2AX. NHEJ reporter assay was to assess DNA repair efficiency. Western blot tested levels of DNA damage repair (DDR)-related proteins. Immunohistochemistry assessed the expression of relevant genes. Finally, an animal model was constructed to investigate the influence of PDK1 expression on LUAD growth. RESULTS: PDK1 was found to be upregulated in LUAD and enhanced DDP resistance by mediating DDR. E2F8 was identified as an upstream transcription factor of PDK1 and was highly expressed in LUAD. Rescue experiments presented that knocking down E2F8 could weaken the promotion of PDK1 overexpression on DDR-mediated DDP resistance in LUAD. In vivo experiments showed that knocking down PDK1 plus DDP significantly reduced the growth of xenograft tumors. CONCLUSION: Our results indicated that the E2F8/PDK1 axis mediated DDR to promote DDP resistance in LUAD. Our findings lead to an improved treatment strategy after drug resistance.
Voltage-dependent K+ (Kv) channels play an important role in restoring the membrane potential to its resting state, thereby maintaining vascular tone. In this study, native smooth muscle cells from rabbit coronary arteries were used to investigate the inhibitory effect of quetiapine, an atypical antipsychotic agent, on Kv channels. Quetiapine showed a concentration-dependent inhibition of Kv channels, with an IC50 of 47.98 ± 9.46 µM. Although quetiapine (50 µM) did not alter the steady-state activation curve, it caused a negative shift in the steady-state inactivation curve. The application of 1 and 2 Hz train steps in the presence of quetiapine significantly increased the inhibition of Kv current. Moreover, the recovery time constants from inactivation were prolonged in the presence of quetiapine, suggesting that its inhibitory action on Kv channels is use (state)-dependent. The inhibitory effects of quetiapine were not significantly affected by pretreatment with Kv1.5, Kv2.1, and Kv7 subtype inhibitors. Based on these findings, we conclude that quetiapine inhibits Kv channels in both a concentration- and use (state)-dependent manner. Given the physiological significance of Kv channels, caution is advised in the use of quetiapine as an antipsychotic due to its potential side effects on cardiovascular Kv channels.
Introducing Holstein cows on Qinghai-Tibetan Plateau is a potential solution to enhance local milk production. However, the relationship between milk quality and altitude in China remains unknown. Therefore, the components and plasmin (PL) system of raw milk from different altitudes (sea level, 1600, 2700, and 3800 m) were investigated. The daily milk production of Holstein cows and PL activity decreased as the altitude increased. However, the components content of raw milk, plasminogen (PLG)/PL ratio, activities of PLG and plasmin activator (PA) increased with altitude. The pasteurization resulted a significant decrease in PA activity of all milk and a significant increase in PL activity in milk collected at higher altitudes (2700 and 3800 m), suggesting the pasteurization was unsuitable for preserving milk at higher altitudes. This study offered references for the production and storage of milk after introducing Holstein cows on Qinghai-Tibetan Plateau.
To investigate the gelation process of direct ultra-high-temperature (UHT) milk, a pilot-scale steam infusion heat treatment was used to process milk samples over a wide temperature of 142-157 °C for 0.116-6 s, followed by storage at 4 °C, 25 °C, and 37 °C. The results of the physicochemical properties of milk showed that the particle sizes and plasmin activities of all milk samples increased during storage at 25 °C, but age gelation only occurred in three treated samples, 147 °C/6 s, 142 °C/6 s, and 142 °C/3 s, which all had lower plasmin activities. Furthermore, the properties of formed gels were further compared and analyzed by the measures of structure and intermolecular interaction. The results showed that the gel formed in the 147 °C/6 s-treated milk with a higher C* value had a denser network structure and higher gel strength, while the 142 °C/6 s-treated milk had the highest porosity. Furthermore, disulfide bonds were the largest contributor to the gel structure, and there were significant differences in disulfide bonds, hydrophobic interaction forces, hydrogen bonds, and electrostatic force among the gels. Our results showed that the occurrence of gel was not related to the thermal load, and the different direct UHT treatments produced different age gels in the milk.
We explored the vasorelaxant effects of ipragliflozin, a sodium-glucose cotransporter-2 inhibitor, on rabbit femoral arterial rings. Ipragliflozin relaxed phenylephrine-induced pre-contracted rings in a dose-dependent manner. Pre-treatment with the ATP-sensitive K+ channel inhibitor glibenclamide (10 µM), the inwardly rectifying K+ channel inhibitor Ba2+ (50 µM), or the Ca2+-sensitive K+ channel inhibitor paxilline (10 µM) did not influence the vasorelaxant effect. However, the voltage-dependent K+ (Kv) channel inhibitor 4-aminopyridine (3 mM) reduced the vasorelaxant effect. Specifically, the vasorelaxant response to ipragliflozin was significantly attenuated by pretreatment with the Kv7.X channel inhibitors linopirdine (10 µM) and XE991 (10 µM), the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) pump inhibitors thapsigargin (1 µM) and cyclopiazonic acid (10 µM), and the cAMP/protein kinase A (PKA)-associated signaling pathway inhibitors SQ22536 (50 µM) and KT5720 (1 µM). Neither the cGMP/protein kinase G (PKG)-associated signaling pathway nor the endothelium was involved in ipragliflozin-induced vasorelaxation. We conclude that ipragliflozin induced vasorelaxation of rabbit femoral arteries by activating Kv channels (principally the Kv7.X channel), the SERCA pump, and the cAMP/PKA-associated signaling pathway independent of other K+ (ATP-sensitive K+, inwardly rectifying K+, and Ca2+-sensitive K+) channels, cGMP/PKG-associated signaling, and the endothelium.
Cyclic AMP-Dependent Protein Kinases , Femoral Artery , Glucosides , Sarcoplasmic Reticulum Calcium-Transporting ATPases , Signal Transduction , Thiophenes , Vasodilation , Animals , Rabbits , Femoral Artery/drug effects , Femoral Artery/physiology , Vasodilation/drug effects , Signal Transduction/drug effects , Cyclic AMP-Dependent Protein Kinases/metabolism , Thiophenes/pharmacology , Male , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism , Sarcoplasmic Reticulum Calcium-Transporting ATPases/antagonists & inhibitors , Vasodilator Agents/pharmacology , Potassium Channels, Voltage-Gated/metabolism , Potassium Channels, Voltage-Gated/antagonists & inhibitors
The electrochemical synthesis of propylene oxide is far from practical application due to the limited performance (including activity, stability, and selectivity). In this work, we spatially decouple the bromide-mediated process to avoid direct contact between the anode and propylene, where bromine is generated at the anode and then transferred into an independent reactor to react with propylene. This strategy effectively prevents the side reactions and eliminates the interference to stability caused by massive alkene input and vigorously stirred electrolytes. As expected, the selectivity for propylene oxide reaches above 99.9% with a remarkable Faradaic efficiency of 91% and stability of 750-h (>30 days). When the electrode area is scaled up to 25 cm2, 262 g of pure propylene oxide is obtained after 50-h continuous electrolysis at 6.25 A. These findings demonstrate that the electrochemical bromohydrin route represents a viable alternative for the manufacture of epoxides.
It is predicted that oxygen minimum zones (OMZs) in the ocean will expand as a consequence of global warming and environmental pollution. This will affect the overall microbial ecology and microbial nitrogen cycle. As one of the world's largest alluvial estuaries, the Yangtze Estuary has exhibited a seasonal OMZ since the 1980s. In this study, we have uncovered the microbial composition, the patterns of community assembly and the potential for microbial nitrogen cycling within the water column of the Yangtze Estuary, with a particular focus on OMZ. Based on the 16 S rRNA gene sequencing, a specific spatial variation in the composition of prokaryotic communities was observed for each water layer, with the Proteobacteria (46.1%), Bacteroidetes (20.3%), and Cyanobacteria (10.3%) dominant. Stochastic and deterministic processes together shaped the community assembly in the water column. Further, pH was the most important environmental factor influencing prokaryotic composition in the surface water, followed by silicate, PO43-, and distance offshore (p < 0.05). Water depth, NH4+, and PO43- were the main factors in the bottom water (p < 0.05). At last, species analysis and marker gene annotation revealed candidate nitrogen cycling performers, and a rich array of nitrogen cycling potential in the bottom water of the Yangtze Estuary. The determined physiochemical parameters and potential for nitrogen respiration suggested that organic nitrogen and NO3- (or NO2-) are the preferred nitrogen sources for microorganisms in the Yangtze Estuary OMZ. These findings are expected to advance research on the ecological responses of estuarine oxygen minimum zones (OMZs) to future global climate perturbations.
Estuaries , Nitrogen , Oxygen , China , Nitrogen/metabolism , Nitrogen/analysis , Oxygen/metabolism , Oxygen/analysis , Bacteria/metabolism , Bacteria/genetics , Bacteria/classification , RNA, Ribosomal, 16S , Nitrogen Cycle
The aberrant activation of the PI3K/mTOR signaling pathway is implicated in various human cancers. Thus, the development of inhibitors targeting mTOR has attracted considerable attention. In this study, we used a structure-based drug design strategy to discover a highly potent and kinase-selective mTOR inhibitor 24 (PT-88), which demonstrated an mTOR inhibitory IC50 value of 1.2 nM without obvious inhibition against another 195 kinases from the kinase profiling screening. PT-88 displayed selective inhibition against MCF-7 cells (IC50: 0.74 µM) with high biosafety against normal cells, in which autophagy induced by mTOR inhibition was implicated. After successful encapsulation in a lipodisc formulation, PT-88 demonstrated favorable pharmacokinetic and biosafety profiles and exerted a large antitumor effect in an MCF-7 subcutaneous bearing nude mice model. Our study shows the discovery of a highly selective mTOR inhibitor using a structure-based drug discovery strategy and provides a promising antitumor candidate for future study and development.
Antineoplastic Agents , Breast Neoplasms , Drug Design , MTOR Inhibitors , Mice, Nude , TOR Serine-Threonine Kinases , Triazines , Humans , Animals , Triazines/chemical synthesis , Triazines/pharmacology , Triazines/chemistry , Triazines/pharmacokinetics , Triazines/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Female , TOR Serine-Threonine Kinases/antagonists & inhibitors , TOR Serine-Threonine Kinases/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Mice , MTOR Inhibitors/pharmacology , MTOR Inhibitors/chemical synthesis , MTOR Inhibitors/therapeutic use , MTOR Inhibitors/chemistry , Structure-Activity Relationship , MCF-7 Cells , Cell Proliferation/drug effects , Xenograft Model Antitumor Assays , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/pharmacokinetics , Mice, Inbred BALB C , Autophagy/drug effects
The vast bulk of polystyrene (PS), a major type of plastic polymers, ends up in landfills, which takes up to thousands of years to decompose in nature. Chemical recycling promises to enable lower-energy pathways and minimal environmental impacts compared with traditional incineration and mechanical recycling. Herein, we demonstrated that methanol as a hydrogen supplier assisted the depolymerization of PS (denoted as PS-MAD) into alkylbenzenes over a heterogeneous catalyst composed of Ru nanoparticles on SiO2. PS-MAD achieved a high yield of liquid products which accounted for 93.2â wt % of virgin PS at 280 °C for 6â h with the production rate of 118.1â mmolcarbon gcatal. -1 h-1. The major components were valuable alkylbenzenes (monocyclic aromatics and diphenyl alkanes), the sum of which occupied 84.3â wt % of liquid products. According to mechanistic studies, methanol decomposition dominates the hydrogen supply during PS-MAD, thereby restraining PS aromatization which generates by-products of fused polycyclic arenes and polyphenylenes.
Syngas conversion serves as a gas-to-liquid technology to produce liquid fuels and valuable chemicals from coal, natural gas, or biomass. During syngas conversion, sintering is known to deactivate the catalyst owing to the loss of active surface area. However, the growth of nanoparticles might induce the formation of new active sites such as grain boundaries (GBs) which perform differently from the original nanoparticles. Herein, we reported a unique Cu-based catalyst, Cu nanoparticles with in situ generated GBs confined in zeolite Y (denoted as activated Cu/Y), which exhibited a high selectivity for C5+ hydrocarbons (65.3â C%) during syngas conversion. Such high selectivity for long-chain products distinguished activated Cu/Y from typical copper-based catalysts which mainly catalyze methanol synthesis. This unique performance was attributed to the GBs, while the zeolite assisted the stabilization through spatial confinement. Specifically, the GBs enabled H-assisted dissociation of CO and subsequent hydrogenation into CHx*. CHx* species not only serve as the initiator but also directly polymerize on Cu GBs, known as the carbide mechanism. Meanwhile, the synergy of GBs and their vicinal low-index facets led to the CO insertion where non-dissociative adsorbed CO on low-index facets migrated to GBs and inserted into the metal-alkyl bond for the chain growth.
OBJECTIVE: The purpose of this study is to evaluate the safety and efficacy of linaclotide and polyethylene glycol (PEG) electrolyte powder in patients with chronic constipation undergoing colonoscopy preparation. PATIENTS AND METHODS: We included 260 patients with chronic constipation who were scheduled to undergo a colonoscopy. They were equally divided into 4 groups using a random number table: 4L PEG, 3L PEG, 3L PEG+L, and 2L PEG+L. The 4 groups were compared based on their scores on the Boston Bowel Preparation Scale (BBPS) and Ottawa Bowel Preparation Quality Scale (OBPQS), adverse reactions during the bowel preparation procedure, colonoscope insertion time, colonoscope withdrawal time, detection rate of adenomas, and their willingness to repeat bowel preparation. RESULTS: In terms of the score of the right half of the colon, the score of the transverse colon, the total score using BBPS, and the total score using OBPQS, the 3L PEG (polyethylene glycol)+L group was superior to groups 3L PEG and 2L PEG+L ( P <0.05), but comparable to the 4L PEG group ( P >0.05). The incidence rate of vomiting was higher in the 4L PEG group than in the 2L PEG+L group ( P <0.05). There was no statistically significant difference in the insertion time of the colonoscope between the 4 groups. The colonoscope withdrawal time in the 3L PEG+L group was shorter than in groups 4L PEG and 3L PEG ( P <0.05) and comparable to that in the 4L PEG group ( P >0.05). There was no statistically significant difference in the rate of adenoma detection among the 4 groups ( P >0.05). The 4L PEG group was the least willing of the 4 groups to undergo repeated bowel preparation ( P <0.05). CONCLUSION: The 3L PEG+L is optimal among the 4 procedures. It can facilitate high-quality bowel preparation, reduce the incidence of nausea during the bowel preparation procedure, and encourage patients to undertake repeated bowel preparation.
Cathartics , Constipation , Peptides , Humans , Cathartics/adverse effects , Powders , Constipation/diagnosis , Constipation/chemically induced , Polyethylene Glycols , Colonoscopy/methods , Electrolytes
Na-ion batteries (NIBs) are sustainable alternatives to Li-ion technologies due to the abundant and widely-distributed resources. However, the most promising cathode materials of NIBs so far, O3 layered oxides, suffer from serious air instability issues, which significantly increases the manufactural cost and carbon footprint because of the long-term use of dry rooms. While some feasible strategies are proposed via case studies, universal design strategies for air-stable cathodes are yet to be established. Herein, the air degradation mechanisms of O3 cathodes are investigated via combined first-principles and experimental approaches, with bond dissociation energy proposed as an effective descriptor for predicting air stability. Experimental validations in various unary, binary, and ternary O3 cathodes confirm that the air stability can indeed be effectively improved via simple compositional design. Guided by the predictive model, the designed material can sustain 30-day air-storage without structural or electrochemical degradation. It is calculated that such air-stable cathodes can significantly reduce both energy consumption (≈4 100 000 kWh) and carbon footprint (≈2200-ton CO2) annually for a 2 GWh NIBs manufactory. Therefore, the fundamental understandings and universal design strategy presented open an avenue for rational materials design of NIBs toward both elemental and manufactural sustainability.
The objective of this study was to investigate the effects of two different organic selenium (Se) supplements, selenomethionine (Se-Met) and selenohomolanthionine (Se-Hlan), on the serum biochemical parameters and Se status of dairy cows. Different dietary Se supplementation treatments were set as follows: a control group (CON, adding sodium selenite at 0.3 mg Se/kg dry matter [DM]), 0.3 and 0.5 Se-Met (adding Se-Met at 0.3 and 0.5 mg Se/kg DM, respectively), as well as 0.3 and 0.5 Se-Hlan (adding Se-Hlan at 0.3 and 0.5 mg Se/kg DM, respectively). The experiment lasted 8 weeks. The serum measurements showed that both organic Se treatments resulted in higher uric acid than CON. Se-Met produced higher aspartate aminotransferase, glucose, urea, low-density lipoprotein cholesterol, and lactate dehydrogenase than Se-Hlan. Regarding the Se status, the highest milk Se values appeared in 0.5 Se-Met, with intermediate values in 0.3 Se-Met and 0.5 Se-Hlan, whereas the highest and lowest serum Se levels were presented in 0.5 Se-Met and 0.3 Se-Hlan, respectively. Our results suggest that Se-Hlan was not as efficient in boosting serum or milk Se as Se-Met and differences in serum biomarkers between Se-Met and Se-Hlan may be associated with distinct metabolic pathways for different forms of organic Se.
Selenium , Female , Cattle , Animals , Dietary Supplements , Milk/metabolism , Selenomethionine/metabolism , Animal Feed/analysis , Biomarkers/metabolism , Diet/veterinary
ETHNOPHARMACOLOGICAL RELEVANCE: Rujifang (RJF) constitutes a traditional Chinese medicinal compound extensively employed in the management of triple-negative breast cancer (TNBC). However, information regarding its potential active ingredients, antitumor effects, safety, and mechanism of action remains unreported. AIM OF THE STUDY: To investigate the efficacy and safety of RJF in the context of TNBC. MATERIALS AND METHODS: We employed the ultra high-performance liquid chromatography-electrospray four-pole time-of-flight mass spectrometry technique (UPLC/Q-TOF-MS/MS) to scrutinize the chemical constituents of RJF. Subcutaneously transplanted tumor models were utilized to assess the impact of RJF on TNBC in vivo. Thirty female BLAB/c mice were randomly divided into five groups: the model group, cyclophosphamide group, and RJF high-dose, medium-dose, and low-dose groups. A total of 1 × 106 4T1 cells were subcutaneously injected into the right shoulder of mice, and they were administered treatments for a span of 28 days. We conducted evaluations on blood parameters, encompassing white blood cell count (WBC), red blood cell count (RBC), hemoglobin (HGB), platelet count (PLT), neutrophils, lymphocytes, and monocytes, as well as hepatorenal indicators including alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), albumin, and creatinine (CRE) to gauge the safety of RJF. Ki67 and TUNEL were detected via immunohistochemistry and immunofluorescence, respectively. We prepared RJF drug-containing serum for TNBC cell lines and assessed the in vitro inhibitory effect of RJF on tumor cell growth through the CCK8 assay and cell cycle analysis. RT-PCR was employed to detect the mRNA expression of cyclin-dependent kinase and cyclin-dependent kinase inhibitors in tumor tissues, and Western blot was carried out to ascertain the expression of cyclin and pathway-related proteins. RESULTS: 100 compounds were identified in RJF, which consisted of 3 flavonoids, 24 glycosides, 18 alkaloids, 3 amino acids, 8 phenylpropanoids, 6 terpenes, 20 organic acids, and 18 other compounds. In animal experiments, both CTX and RJF exhibited substantial antitumor effects. RJF led to an increase in the number of neutrophils in peripheral blood, with no significant impact on other hematological indices. In contrast, CTX reduced red blood cell count, hemoglobin levels, and white blood cell count, while increasing platelet count. RJF exhibited no discernible influence on hepatorenal function, whereas Cyclophosphamide (CTX) decreased ALP, GOT, and GPT levels. Both CTX and RJF reduced the expression of Ki67 and heightened the occurrence of apoptosis in tumor tissue. RJF drug-containing serum hindered the viability of 4T1 and MD-MBA-231 cells in a time and concentration-dependent manner. In cell cycle experiments, RJF diminished the proportion of G2 phase cells and arrested the cell cycle at the S phase. RT-PCR analysis indicated that RJF down-regulated the mRNA expression of CDK2 and CDK4, while up-regulating that of P21 and P27 in tumor tissue. The trends in CDKs and CDKIs protein expression mirrored those of mRNA expression. Moreover, the PI3K/AKT pathway displayed downregulation in the tumor tissue of mice treated with RJF. CONCLUSION: RJF demonstrates effectiveness and safety in the context of TNBC. It exerts anti-tumor effects by arresting the cell cycle at the S phase through the PI3K-AKT pathway.
Signal Transduction , Triple Negative Breast Neoplasms , Humans , Female , Animals , Mice , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Triple Negative Breast Neoplasms/pathology , Ki-67 Antigen/metabolism , Tandem Mass Spectrometry , Cell Line, Tumor , Cell Proliferation , Apoptosis , Cyclin-Dependent Kinases/metabolism , Cyclin-Dependent Kinases/pharmacology , Cyclin-Dependent Kinases/therapeutic use , Cyclophosphamide/pharmacology , Hemoglobins/pharmacology , Hemoglobins/therapeutic use , Transaminases , Glutamates/pharmacology , Glutamates/therapeutic use , RNA, Messenger
Methane oxidation using molecular oxygen remains a grand challenge in which the obstacle is not only the activation of methane but also the reaction with oxygen, considering the mismatch of the ground spin states. Herein, we report TiO2-supported Pt nanocrystals (Pt/TiO2) with surface Pt-Ti alloyed layers that directly convert methane into oxygenates by using O2 as the oxidant with the assistance of CO. The oxygenate yield reached 749.8 mmol gPt-1 in a H2O aqueous solution over 0.1% Pt/TiO2 under 31 bar of mixed gas (20:5:6 CH4:CO:O2) at 150 °C for 3 h, while the CH3OH selectivity was 62.3%. On the basis of the control experiments and spectroscopic results, we identified the surface Pt-Ti alloy as the active sites. Moreover, CO promoted the dissociation of O2 on the surface of Pt-Ti alloyed layers and the subsequent activation of CH4 to form oxygenated products.
