Electroacupuncture at different intensities inhibits nociceptive discharges of wide dynamic range neurons in spinal dorsal horn of rats. / ä¸åŒå¼ºåº¦ç”µé’ˆå¯¹å¤§é¼ è„Šé«“èƒŒè§’å¹¿åŠ¨åŠ›ç¥žç»å ƒä¼¤å®³æ€§æ”¾ç”µçš„æŠ‘åˆ¶ä½œç”¨.

OBJECTIVES: To observe the effect of electroacupuncture (EA) at different intensities on nociceptive discharges of wide dynamic range (WDR) neurons in the spinal dorsal horns (DHs) of rats, so as to explore its regulatory characteristics on nociceptive signals at the spinal level. METHODS: A total of 25 male SD rats were used in the present study. A microelectrode array was used to record the discharge activity of WDR neurons in the lumbar spinal DHs of normal rats. After finding the WDR neuron, electrical stimulation (pulse width of 2 ms) was administered to the plantar receptive field (RF) for determining its response component of discharges according to the latency of action potential generation (Aß ï¼»0 to 20 msï¼½, Aδ ï¼»20 to 90 msï¼½, C ï¼»90 to 500 msï¼½ and post-discharge ï¼»500 to 800 msï¼½). High-intensity electrical stimulation was continuously applied to the RF at the paw's plantar surface to induce DHs neuronal windup response. Subsequently, EA stimulation at different intensities (1 mA and 2 mA) was applied to the left "Zusanli"(ST36) at a frequency of 2 Hz/15 Hz for 10 min. The induction of WDR neuronal windup was then repeated under the same conditions. The quantity of nociceptive discharge components and the windup response of WDR neurons before and after EA stimulations at different intensities were compared. RESULTS: Compared to pre-EA, both EA1 mA and EA2 mA significantly reduced the number of Aδ and C component discharges of WDR neurons during stimulation, as well as post-discharge (P<0.01, P<0.001). The inhibitory rate of C component by EA2 mA was significantly higher than that by EA1 mA (P<0.05). Meanwhile, both EA1 mA and EA2 mA attenuated the windup response of WDR neurons (P<0.05, P<0.01), and the effect of EA2 mA was stronger than that of EA1 mA (P<0.05). Further analysis showed that when EA1 mA and EA2 mA respectively applied to both non-receptive field (non-RF) and RF, a significant reduction in the number of Aδ component, C component and post-discharge was observed (P<0.05, P<0.01). EA2 mA at the non-RF and RF demonstrated a significant inhibitory effect on the windup response of WDR neurons (P<0.01, P<0.05), but EA1 mA only at the non-RF showed a significant inhibitory effect on the windup response (P<0.01). CONCLUSIONS: EA can suppress nociceptive discharges of spinal DHs WDR neurons in rats. The inhibitory impact of EA is strongly correlated with the location and intensity of EA stimulation, and EA2 mA has a stronger inhibitory effect than EA1 mA.

Efficient degradation of venlafaxine using intimately coupled high-active crystal facets exposed TiO2 and biodegradation system: Kinetic studies, biofilm stress behavior and transformation mechanism.

Intimately coupled photocatalysis and biodegradation (ICPB) system is a potential wastewater treatment technology, of which TiO2-based ICPB system has been widely studied. There are many ways to improve the degradation efficiency of the ICPB process, but no crystal facet engineering method has been reported yet. In this work, a new ICPB system coated with NaF-TiO2 exposing high energy facets was designed to degrade biorecalcitrant psychotropic drug - venlafaxine (VNF). Initially, the TiO2 crystal surface was modified with NaF, resulting in the formation of NaF-TiO2 with a 14.4% increase in the exposure ratio of (001). The contribution rate of ·OH was increased by 9.5%, and the contribution rate of h+ was increased by 33.2%. Next, NaF-TiO2 was loaded onto the surface of the sponge carrier, and then the ICPB system was constructed after about 15 days of biofilm formation. After the ICPB system was acclimated with VNF, the removal rate of COD decreased significantly (the lowest was 62.7%), but that of ammonia nitrogen remained at 50.5 ± 6.0% and the extracellular polymeric substance (EPS) secretion increased by 84.1 mg/g VSS. According to the high throughput results, at the phylum level, Proteobacteria and Chloroflexi together maintain the nitrogen removal capability and structural stability of the ICPB system. The relative abundance of Bacteroidota was significantly increased by 14.2%, suggesting that there may be some correlation between Bacteroidota and certain metabolites of the anti-depressant active ingredients. At the genus level, the Thauera (3.1%∼11.5%) is the major bacterial group that secretes EPS, protecting biofilm against external influences. Most of the changes in microorganisms are consistent with the decontamination properties and macroscopic appearance of EPS in the ICPB system. Finally, the degradation efficiency of ICPB system for VNF was investigated (92.7 ± 3.8%) and it was mostly through hydroxylation and demethylation pathways, with more small molecular products detected, providing the basis for biological assimilation of VNF. Collectively, the NaF-TiO2 based ICPB system would be lucrative for the future degradation of venlafaxine.

Origins of Ligand-Controlled Stereoselective Polymerization of ortho-Methoxystyrene by Rare-Earth Catalysts: A Theoretical Perspective.

The stereoselective polymerization of polar vinyl monomers has recently received much attention due to their excellent physicochemical properties. Over the past decade, breakthroughs have been achieved in this field by rare-earth catalysts. However, the mechanistic origins of those stereoselective polymerizations still remain unclear. Herein, stereoselective polymerization of ortho-methoxystyrene (oMOS) by several representative rare-earth catalysts bearing different ligands (i.e., η5-C5Me5, pyridinyl-methylene-fluorenyl, quinolyl-anilido, ß-diketiminato) were systematically investigated by density functional theory (DFT) calculations. After achieving agreement between the calculations and experiments, we focused on discussing the role of ligands in controlling stereoselectivity. Our results reveal that the stereoregularity of oMOS polymerization is mainly controlled by the steric effect of the catalyst-monomer structures. Specifically, the type of ligand influences the orientation and configuration of the inserting monomer, thereby affecting the tacticity of the polymers. In the cases of η5-C5Me5-, pyridinyl-methylene-fluorenyl, and quinolyl-anilido-ligated yttrium catalysts, we observe consistent insertion directions and alternating insertion sides of oMOS monomers, leading to syndiotactic selectivity. The opposite insertion directions and the alternating insertion sides of oMOS monomers were observed in the case of the ß-diketiminato yttrium catalyst, leading to isotactic selectivity. These findings reported here offer valuable insights into the role of ligands in controlling stereoselectivity in rare-earth catalyzed coordination polymerization of polar vinyl monomers, thus providing guidance for the rational design of new ligands for stereospecific polymerization of polar monomers in the future.

Emergence and ongoing outbreak of ST80 vancomycin-resistant Enterococcus faecium in Guangdong province, China from 2021 to 2023: a multicenter, time-series and genomic epidemiological studyEpidemiology of vancomycin-resistant Enterococcus faecium.

BACKGROUND: Surveillance systems revealed that the prevalence of vancomycin-resistant Enterococcus faecium (VREfm) has increased. We aim to investigate the epidemiological and genomic characteristics of VREfm in China. METHODS: We collected 20747 non-redundant E. faecium isolates from inpatients across 19 hospitals in six provinces between Jan 2018 and June 2023. VREfm was confirmed by antimicrobial susceptibility testing. The prevalence was analyzed using changepoint package in R. Genomic characteristics were explored by whole-genome sequencing. RESULTS: 5.59% (1159/20747) of E. faecium isolates were resistant to vancomycin. The prevalence of VREfm increased in Guangdong province from 5% before 2021 to 20%-50% in 2023 (p < 0.0001), but not in the other five provinces. Two predominant clones before 2021, ST17 and ST78, were substituted by an emerging clone, ST80, from 2021 to 2023 (88.63%, 195/220). All ST80 VREfm from Guangdong formed a single lineage (SC11) and were genetically distant from the ST80 VREfm from other countries, suggesting a regional outbreak. All ST80 VREfm in SC11 carried a new type of plasmid harboring a vanA cassette, which was embedded in a Tn1546-like structure flanked by IS1678 and ISL3. However, no conjugation-related gene was detected and no transconjugant was obtained in conjugation experiment, indicating that the outbreak of ST80 VREfm could be attributed to clonal transmission. CONCLUSIONS: We revealed an ongoing outbreak of ST80 VREfm with a new vanA-harboring plasmid in Guangdong, China. This clone has also been identified in other provinces and countries, foreboding a risk of wider spreading shortly. Continuous surveillance is needed to inform public health interventions.

Polyphyllin I ameliorates gefitinib resistance and inhibits the VEGF/VEGFR2/p38 pathway by targeting HIF-1a in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been administered as the first-line therapy for patients with EGFR mutations in LUAD, but it is almost inevitable that resistance to EGFR-TKIs therapy eventually arises. Polyphyllin I (PPI), derived from Paris polyphylla rhizomes, has been shown to have potent anti-cancer properties in a range of human cancer types including LUAD. However, the role of PPI in gefitinib resistance and the underlying mechanism remain elusive. PURPOSE: To evaluate the antitumor impacts of PPI on gefitinib resistance cells and investigate its molecular mechanism. METHODS: CCK-8, wound healing, transwell assay, and xenograft model were performed to determine the anti-cancer effects of PPI as well as its ability to overcome gefitinib resistance. Immunoblotting, co-immunoprecipitation, phospho-RTK antibody array, qRT-PCR, and immunofluorescence were utilized to explore the mechanism by which PPI overrides gefitinib resistance. RESULTS: PPI inhibited cell survival, growth, and migration/invasion in both gefitinib-sensitive (PC9) and -resistant (PC9/GR) LUAD cells (IC50 at 2.0 µM). Significantly, treatment with PPI at 1.0 µM resensitized the resistant cells to gefitinib. Moreover, cell-derived xenograft experiments revealed that the combination of PPI and gefitinib overcame gefitinib resistance. The phospho-RTK array and immunoblotting analyses showed PPI significant inhibition of the VEGFR2/p38 pathway. In addition, molecular docking suggested the interaction between PPI and HIF-1α. Mechanistically, PPI reduced the protein expression of HIF-1α in both normoxia and hypoxia conditions by triggering HIF-1α degradation. Moreover, HIF-1α protein but not mRNA level was elevated in gefitinib-resistant LUAD. We further demonstrated that PPI considerably facilitated the binding of HIF-1α to VHL. CONCLUSIONS: We present a novel discovery demonstrating that PPI effectively counteracts gefitinib resistance in LUAD by modulating the VEGF/VEGFR2/p38 pathway. Mechanistic investigations unveil that PPI facilitates the formation of the HIF-1α /VHL complex, leading to the degradation of HIF-1α and subsequent inhibition of angiogenesis. These findings uncover a previously unidentified mechanism governing HIF-1α expression in reaction to PPI, providing a promising method for therapeutic interventions targeting EGFR-TKI resistance in LUAD.

Response Mechanism of cbbM Carbon Sequestration Microbial Community Characteristics in Different Wetland Types in Qinghai Lake.

Carbon-sequestering microorganisms play an important role in the carbon cycle of wetland ecosystems. However, the response mechanism of carbon-sequestering microbial communities to wetland type changes and their relationship with soil carbon remain unclear. To explore these differences and identify the main influencing factors, this study selected marsh wetlands, river wetlands and lakeside wetlands around Qinghai Lake as research subjects. High-throughput sequencing was employed to analyze the functional gene cbbM of carbon-sequestering microorganisms. The results revealed that the alpha diversity of cbbM carbon-sequestering microorganisms mirrored the trend in total carbon content, with the highest diversity observed in marsh wetlands and the lowest in lakeside wetlands. The dominant bacterial phylum was Proteobacteria, with prevalent genera including Thiothrix, Acidithiobacillus, and Thiodictyon. Acidithiobacillus served as a biomarker in lakeside wetlands, while two other genera were indicative of marsh wetlands. The hierarchical partitioning analysis indicated that the diversity of cbbM carbon-fixing microorganisms was primarily influenced by the total nitrogen content, while the community structure was significantly affected by the soil total carbon content. Moreover, an increased soil temperature and humidity were found to favor the carbon fixation processes of Thiomicrospira, Thiomonas, Polaromonas, and Acidithiobacillus. In summary, changes in wetland types seriously affected the characteristics of cbbM carbon sequestration in microbial communities, and a warm and humid climate may be conducive to wetland carbon sequestration.

The digestion and dietary carbohydrate pathway contains 100% gene mutations enrichment among 117 patients with major depressive disorder.

Introduction: Major depressive disorder (MDD) is partially inheritable while its mechanism is still uncertain. Methods: This cross-sectional study focused on gene pathways as a whole rather than polymorphisms of single genes. Deep sequencing and gene enrichment analysis based on pathways in Reactome database were obtained to reveal gene mutations. Results: A total of 117 patients with MDD and 78 healthy controls were enrolled. The Digestion and Dietary Carbohydrate pathway (Carbohydrate pathway) was determined to contain 100% mutations in patients with MDD and 0 mutation in matched healthy controls. Discussion: Findings revealed in the current study enable a better understanding of gene pathways mutations status in MDD patients, indicating a possible genetic mechanism of MDD development and a potential diagnostic or therapeutic target.

The impact of continuous cultivation of Ganoderma lucidum on soil nutrients, enzyme activity, and fruiting body metabolites.

To explore the impacts of continuous Ganoderma lucidum cultivation on soil physicochemical factors, soil enzyme activity, and the metabolome of Ganoderma lucidum fruiting bodies, this study conducted two consecutive years of cultivation on the same plot of land. Soil physicochemical factors and enzyme activity were assessed, alongside non-targeted metabolomic analysis of the Ganoderma lucidum fruiting bodies under continuous cultivation. The findings unveiled that in the surface soil layer (0-15 cm), there was a declining trend in organic matter, ammonium nitrogen, available phosphorus, available potassium, pH, polyphenol oxidase, peroxidase, alkaline phosphatase, and sucrase, whereas nitrate nitrogen, electrical conductivity (EC), and salt content exhibited an upward trend. Conversely, in the deeper soil layer (15-30 cm), organic matter, ammonium nitrogen, available potassium, alkaline phosphatase, and sucrase demonstrated a decreasing trend, while nitrate nitrogen, available phosphorus, pH, EC, salt content, polyphenol oxidase, and soil peroxidase showed an increasing trend. Metabolomic analysis of Ganoderma lucidum fruiting bodies distinguished 64 significantly different metabolites between the GCK and GT groups, with 39 components having markedly higher relative contents in GCK and 25 components having significantly lower relative contents in GCK compared to GT. Moreover, among these metabolites, there were more types with higher contents in the fruiting bodies harvested in the first year (GCK) compared to those harvested in the second year (GT), with pronounced differences. KEGG pathway analysis revealed that GCK exhibited more complex metabolic pathways compared to GT. The metabolites of Ganoderma lucidum fruiting bodies were predominantly influenced by soil physicochemical factors and soil enzyme activity. In the surface soil layer (0-15 cm), the metabolome was significantly affected by soil pH, soil organic matter, available phosphorus, and soil alkaline phosphatase, while in the deeper soil layer (15-30 cm), differences in the Ganoderma lucidum metabolome were more influenced by soil alkaline phosphatase, soil catalase, pH, nitrate nitrogen, and soil sucrase.

Vertical differentiation drives the changes in the main microflora and metabolites of carbon and nitrogen cycling in the early freeze-thaw period in the Qinghai Lake Basin.

Global climate change has altered the frequency of soil freeze-thaw cycles, but the response of soil microorganisms to different elevation gradients during the early freeze-thaw period remains unclear. So far, the influence of the altitudinal gradient on the microbial community and metabolic characteristics in the early freeze-thaw period of the Qinghai Lake Basin remains unclear. To this end, we collected soil at different elevations in the early freeze-thaw period of the Qinghai Lake Basin and investigated the influence of the elevation gradient on soil microbial community characteristics and soil metabolic processes as well as the corresponding environmental driving mechanism by high-throughput sequencing and LC-MS (Liquid Chromatograph-Mass Spectrometer) nontargeted metabolite determination. The results showed that Proteobacteria were the dominant microflora in the Qinghai Lake Basin. The dominant phyla associated with carbon and nitrogen are Proteobacteria and Firmicutes, both of which are significantly affected by elevation. The soil physicochemical factors jointly affected the soil microbial communities and metabolism. Total phosphorus nitrate nitrogen and pH were the main driving factors of the microbial community, and metabolites were sensitive to changes in chemical factors. In short, the microbial community structure and function, soil physicochemical factors and soil metabolic processes were significantly affected by the altitudinal gradient in the early freeze-thaw period, while the microbial community diversity showed no significant response to the altitudinal gradient. Additionally, a high potassium content in the soil may promote the growth and reproduction of bacteria associated with carbon and nitrogen cycling, as well as the production of metabolites.

Altitudinal variation of dragon fruit metabolite profiles as revealed by UPLC-MS/MS-based widely targeted metabolomics analysis.

BACKGROUND: Geographical factors affect the nutritional, therapeutic and commercial values of fruits. Dragon fruit (Hylocereus spp) is a popular fruit in Asia and a potential functional food with diverse pharmacological attributes. Although it is produced in various localities, the information related to the altitudinal variation of dragon fruit nutrients and active compounds is scarce. Hence, this study aimed to investigate the variations in metabolite profiles of H. polyrhizus (variety Jindu1) fruit pulps from three different altitudes of China, including Wangmo (WM, 650 m), Luodian (LD, 420 m), and Zhenning (ZN, 356 m). Jindu1 is the main cultivated pitaya variety in Guizhou province, China. RESULTS: The LC-MS (liquid chromatography-mass spectroscopy)-based widely targeted metabolic profiling identified 645 metabolites, of which flavonoids (22.64%), lipids (13.80%), phenolic acids (12.40%), amino acids and derivatives (10.39%), alkaloids (8.84%), and organic acids (8.37%) were dominant. Multivariate analyses unveiled that the metabolite profiles of the fruit differed regarding the altitude. Fruits from WM (highest altitude) were prime in quality, with higher levels of flavonoids, alkaloids, nucleotides and derivatives, amino acids and derivatives, and vitamins. Fruits from LD and ZN had the highest relative content of phenolic acids and terpenoids, respectively. We identified 69 significantly differentially accumulated metabolites across the pulps of the fruits from the three locations. KEGG analysis revealed that flavone and flavonol biosynthesis and isoflavonoid biosynthesis were the most differentially regulated. It was noteworthy that most active flavonoid compounds exhibited an increasing accumulation pattern along with the increase in altitude. Vitexin and isovitexin were the major differentially accumulated flavonoids. Furthermore, we identified two potential metabolic biomarkers (vitexin and kaempferol 3-O-[2-O-ß-D-galactose-6-O-a-L-rhamnose]-ß-D-glucoside) to discriminate between dragon fruits from different geographical origins. CONCLUSION: Our findings provide insights into metabolic changes in dragon fruits grown at different altitudes. Furthermore, they show that growing pitaya at high altitudes can produce fruit with higher levels of bioactive compounds, particularly flavonoids.

Mechanistic Insights into Rare-Earth-Catalyzed Alternating Copolymerization through C-H Polyaddition of Functionalized Organic Compounds to Unconjugated Dienes.

Density functional theory (DFT) calculations have been conducted to elucidate the detailed mechanisms of yttrium-catalyzed C-H polyaddition of 1,4-dimethoxybenzene (DMB) to 1,4-divinylbenzene (DVB). It was computationally determined that DMB not only serves as a substrate but also performs a crucial role as a ligand, stabilizing the catalytically active species and promoting alkene insertion. Side pathways involving Cß-H activation and C═C continuous insertion were excluded due to steric and electronic factors, respectively, explaining why the reaction occurred efficiently and selectively to give perfectly alternating DMB-DVB polymers. Interestingly, the theoretical prediction of the reactivity of N,N-dimethyl-1,4-phenylenediamine and 2,2'-biethyl-4,4'-bipyridine reveals significant differences in the coordination effects of these substrates, leading to distinct mechanisms, primarily influenced by their steric effects. These findings shed new light on the previously overlooked role of substrate ligand effects in rare-earth-catalyzed step-growth copolymerization reactions.

Arterial embolization in the treatment of multiple renal and hepatic hamartomas with spontaneous hemorrhage and 2-year follow-up: a case report.

BACKGROUND: Hamartoma is a common benign tumor that usually occurs in the kidney, liver, lung, and pancreas. Large renal hamartomas may spontaneously rupture and hemorrhage, which is potentially life-threatening. CASE PRESENTATION: This report describes a 46-year-old Han Chinese female patient with multiple renal and hepatic hamartomas with rupture and hemorrhage of giant hamartoma in the left kidney. She underwent arterial embolization three times successively, and her condition was stable during the 2-year follow-up. This report includes a review of the relevant literature CONCLUSIONS: the findings in this report and previous literature suggest that arterial embolization can not only rapidly treat hamartoma hemorrhage in the acute phase but can also effectively control multiple lesions in the long term after repeated multisite arterial embolization.

Automated infrared ashing with palladium nitrate as an ashing aid for the determination of selenium in plant foods by inductively coupled plasma mass spectrometry.

Based on the automatic light wave ashing instrument, palladium nitrate was used as an ashing aid for the first time to collect selenium in the process of food ashing pre-treatment, and a method for the determination of selenium in food by ashing method was established with inductively coupled plasma mass spectrometry. At the same time, the effects of magnesium nitrate, rhodium nitrate, and nickel nitrate as ashing aids on selenium collection were investigated using certified plant standard materials. The capture of selenium by magnesium nitrate, rhodium nitrate, and nickel nitrate as ashing aids did not exceed 50%. Using palladium nitrate as an ashing aid, six food standard materials were measured, with selenium recovery rates ranging from 97 to 106%. A complete analysis cycle can be completed within an hour. The method detection limit of selenium was 0.021 µg g-1, and the relative standard deviation of five measurements was less than 7%. The experimental results show that palladium nitrate is an excellent ashing aid for capturing selenium, and it is far superior to the other three aids. In addition, the mechanism of palladium nitrate as an ashing aid for capturing selenium was discussed.

Age-related changes in meningeal lymphatic function are closely associated with vascular endothelial growth factor-C expression.

Meningeal lymphatic vessels (MLVs) have crucial roles in removing metabolic waste and toxic proteins from the brain and transporting them to the periphery. Aged mice show impaired meningeal lymphatic function. Nevertheless, as the disease progresses, and significant pathological changes manifest in the brain, treating the condition becomes increasingly challenging. Therefore, investigating the alterations in the structure and function of MLVs in the early stages of aging is critical for preventing age-related central nervous system degenerative diseases. We detected the structure and function of MLVs in young, middle-aged, and aged mice. Middle-aged mice, compared with young and aged mice, showed enhanced meningeal lymphatic function along with MLV expansion and performed better in the Y maze test. Moreover, age-related changes in meningeal lymphatic function were closely associated with vascular endothelial growth factor-C (VEGF-C) expression in the brain cortex. Our data suggested that the cerebral cortex may serve as a target for VEGF-C supplementation to ameliorate meningeal lymphatic dysfunction, thus providing a new strategy for preventing age-related central nervous system diseases.

Cascade-Catalyzed Nanogel for Amplifying Starvation Therapy by Nitric Oxide-Mediated Hypoxia Alleviation.

Glucose oxidase (Gox)-mediated starvation therapy offers a prospective advantage for malignancy treatment by interrupting the glucose supply to neoplastic cells. However, the negative charge of the Gox surface hinders its enrichment in tumor tissues. Furthermore, Gox-mediated starvation therapy infiltrates large amounts of hydrogen peroxide (H2O2) to surround normal tissues and exacerbate intracellular hypoxia. In this study, a cascade-catalyzed nanogel (A-NE) was developed to boost the antitumor effects of starvation therapy by glucose consumption and cascade reactive release of nitric oxide (NO) to relieve hypoxia. First, the surface cross-linking structure of A-NE can serve as a bioimmobilization for Gox, ensuring Gox stability while improving the encapsulation efficiency. Then, Gox-mediated starvation therapy efficiently inhibited the proliferation of tumor cells while generating large amounts of H2O2. In addition, covalent l-arginine (l-Arg) in A-NE consumed H2O2 derived from glucose decomposition to generate NO, which augmented starvation therapy on metastatic tumors by alleviating tumor hypoxia. Eventually, both in vivo and in vitro studies indicated that nanogels remarkably inhibited in situ tumor growth and hindered metastatic tumor recurrence, offering an alternative possibility for clinical intervention.

Identification of key regulatory molecules in the early development stage of Alzheimer's disease.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, the incidence of which increases with age, and the pathological changes in the brain are irreversible. Recent studies have highlighted the essential role of long noncoding RNAs (lncRNAs) in AD by acting as competing endogenous RNAs (ceRNAs). Our aim was to construct lncRNA-associated ceRNA regulatory networks composed of potential biomarkers for the early stage of AD. AD related datasets come from AlzData and GEO databases. The R package 'Limma' identifies differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases for functional enrichment analysis. Protein-protein interactions (PPIs) in DEGs were constructed in the STRING database, and Cytoscape software identified DEGs. Convergent functional genomics (CFG) analysis of differentially expressed hub genes (referred to as early-DEGs) in the brain before the development of AD pathology. The AlzData database analyses the expression levels of early-DEGs in different nerve cells. The lncRNA-miRNA-mRNA regulatory network was established according to the ceRNA hypothesis. We identified four lncRNAs (XIST, NEAT1, KCNQ1OT1 and HCG18) and four miRNAs (hsa-let-7c-5p, hsa-miR-107, hsa-miR-129-2-3p and hsa-miR-214-3p) were preliminarily identified as potential biomarkers for early AD, competitively regulating Atp6v0b, Atp6v1e1 Atp6v1f and Syt1. This study indicates that NEAT1, XIST, HCG18 and KCNQ1OT1 act as ceRNAs in competitive binding with miRNAs to regulate the expression of Atp6v0b, Atp6v1e1, Atp6v1f and Syt1 before the occurrence of pathological changes in AD.

Advancements in the Cultivation, Active Components, and Pharmacological Activities of Taxus mairei.

Taxus mairei (Lemée and H.Lév.) S.Y.Hu, indigenous to the southern regions of China, is an evergreen tree belonging to the genus Taxus of the Taxaceae family. Owing to its content of various bioactive compounds, it exhibits multiple pharmacological activities and has been widely applied in clinical medicine. This article comprehensively discusses the current state of cultivation, chemical constituents, applications in the pharmaceutical field, and the challenges faced by T. mairei. The paper begins by detailing the ecological distribution of T. mairei, aiming to provide an in-depth understanding of its origin and cultivation overview. In terms of chemical composition, the article thoroughly summarizes the extracts and monomeric components of T. mairei, unveiling their pharmacological activities and elucidating the mechanisms of action based on the latest scientific research, as well as their potential as lead compounds in new drug development. The article also addresses the challenges in the T. mairei research, such as the difficulties in extracting and synthesizing active components and the need for sustainable utilization strategies. In summary, T. mairei is a rare species important for biodiversity conservation and demonstrates significant research and application potential in drug development and disease treatment.

Inducing mitochondriopathy-like damages by transformable nucleopeptide nanoparticles for targeted therapy of bladder cancer.

Mitochondriopathy inspired adenosine triphosphate (ATP) depletions have been recognized as a powerful way for controlling tumor growth. Nevertheless, selective sequestration or exhaustion of ATP under complex biological environments remains a prodigious challenge. Harnessing the advantages of in vivo self-assembled nanomaterials, we designed an Intracellular ATP Sequestration (IAS) system to specifically construct nanofibrous nanostructures on the surface of tumor nuclei with exposed ATP binding sites, leading to highly efficient suppression of bladder cancer by induction of mitochondriopathy-like damages. Briefly, the reported transformable nucleopeptide (NLS-FF-T) self-assembled into nuclear-targeted nanoparticles with ATP binding sites encapsulated inside under aqueous conditions. By interaction with KPNA2, the NLS-FF-T transformed into a nanofibrous-based ATP trapper on the surface of tumor nuclei, which prevented the production of intracellular energy. As a result, multiple bladder tumor cell lines (T24, EJ and RT-112) revealed that the half-maximal inhibitory concentration (IC50) of NLS-FF-T was reduced by approximately 4-fold when compared to NLS-T. Following intravenous administration, NLS-FF-T was found to be dose-dependently accumulated at the tumor site of T24 xenograft mice. More significantly, this IAS system exhibited an extremely antitumor efficacy according to the deterioration of T24 tumors and simultaneously prolonged the overall survival of T24 orthotopic xenograft mice. Together, our findings clearly demonstrated the therapeutic advantages of intracellular ATP sequestration-induced mitochondriopathy-like damages, which provides a potential treatment strategy for malignancies.

Unveiling the Detailed Mechanism and Origins of Chemo-, Regio-, and Stereoselectivity of Rare-Earth Catalyzed Alternating Copolymerization of Polar and Nonpolar Olefins.

The direct copolymerization of polar and nonpolar olefins is of great interest and significance, as it is the most atom-economical and straightforward strategy for the synthesis of functional polyolefin materials. Despite considerable efforts, the precise control of monomer-sequence and their regio- and stereochemistry is full of challenges, and the related mechanistic origins are still in their infancy to date. Herein, the mechanistic studies on the model reaction of Sc-catalyzed co-syndiospecific alternating copolymerization of anisylpropylene (AP) and styrene were performed by DFT calculations. The results suggest that the subtle balance between electronic and steric factors plays an important role during monomer insertions, and a new amino-dissociated mechanism was proposed for AP insertion at chain initiation. AP insertion follows the 2,1-si-insertion pattern, which is mainly controlled by steric factors caused by the restricted MeO···Sc interaction. As for styrene insertion, it prefers the 2,1-re-insertion manner and its regio- and stereoselectivities are influenced by steric repulsions between the inserting styrene and the polymer chain or the ligand. More interestingly, it is found that the alternating monomer-sequence is mainly determined by the "steric matching" principle, which is quantitatively expressed by the buried volume of the metal center of the preinserted species. The concept of steric pocket has been successfully applied to explain the different performances of several catalysts and other alternating copolymerization reactions. The insightful mechanistic findings and the quantitative steric pocket model present here are expected to promote rational design of new rare-earth catalysts for developing regio-, stereo-, and sequence-controlled copolymerization of specific polar and nonpolar olefins.

Two new species of Erythroneurini (Hemiptera, Cicadellidae, Typhlocybinae) from southern China based on morphology and complete mitogenomes.

Erythroneurine leafhoppers (Hemiptera, Cicadellidae, Typhlocybinae, Erythroneurini) are utilized to resolve the relationship between the four erythroneurine leafhopper (Hemiptera, Cicadellidae, Typhlocybinae, Erythroneurini): Arboridia (Arboridia) rongchangensis sp. nov., Thaia (Thaia) jiulongensis sp. nov., Mitjaevia bifurcata Luo, Song & Song, 2021 and Mitjaevia diana Luo, Song & Song, 2021, the two new species are described and illustrated. The mitochondrial gene sequences of these four species were determined to update the mitochondrial genome database of Erythroneurini. The mitochondrial genomes of four species shared high parallelism in nucleotide composition, base composition and gene order, comprising 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), two ribosomal RNAs (rRNAs) and an AT control region, which was consistent with majority of species in Cicadellidae; all genes revealed common trait of a positive AT skew and negative GC skew. The mitogenomes of four species were ultra-conservative in structure, and which isanalogous to that of others in size and A + T content. Phylogenetic trees based on the mitogenome data of these species and another 24 species were built employing the maximum likelihood and Bayesian inference methods. The results indicated that the four species belong to the tribe Erythroneurini, M. diana is the sister-group relationship of M. protuberanta + M. bifurcata. The two species Arboridia (Arboridia) rongchangensis sp. nov. and Thaia (Thaia) jiulongensis sp. nov. also have a relatively close genetic relationship with the genus Mitjaevia.