Layered subsurface in Utopia Basin of Mars revealed by Zhurong rover radar.

Exploring the subsurface structure and stratification of Mars advances our understanding of Martian geology, hydrological evolution and palaeoclimatic changes, and has been a main task for past and continuing Mars exploration missions1-10. Utopia Planitia, the smooth plains of volcanic and sedimentary strata that infilled the Utopia impact crater, has been a prime target for such exploration as it is inferred to have hosted an ancient ocean on Mars11-13. However, 45 years have passed since Viking-2 provided ground-based detection results. Here we report an in situ ground-penetrating radar survey of Martian subsurface structure in a southern marginal area of Utopia Planitia conducted by the Zhurong rover of the Tianwen-1 mission. A detailed subsurface image profile is constructed along the roughly 1,171 m traverse of the rover, showing an approximately 70-m-thick, multi-layered structure below a less than 10-m-thick regolith. Although alternative models deserve further scrutiny, the new radar image suggests the occurrence of episodic hydraulic flooding sedimentation that is interpreted to represent the basin infilling of Utopia Planitia during the Late Hesperian to Amazonian. While no direct evidence for the existence of liquid water was found within the radar detection depth range, we cannot rule out the presence of saline ice in the subsurface of the landing area.

A distinct subset of urothelial cells with enhanced EMT features promotes chemotherapy resistance and cancer recurrence by increasing COL4A1-ITGB1 mediated angiogenesis.

Drug resistance and tumor recurrence remain clinical challenges in the treatment of urothelial carcinoma (UC). However, the underlying mechanism is not fully understood. Here, we performed single-cell RNA sequencing and identified a subset of urothelial cells with epithelial-mesenchymal transition (EMT) features (EMT-UC), which is significantly correlated with chemotherapy resistance and cancer recurrence. To validate the clinical significance of EMT-UC, we constructed EMT-UC like cells by introducing overexpression of two markers, Zinc Finger E-Box Binding Homeobox 1 (ZEB1) and Desmin (DES), and examined their histological distribution characteristics and malignant phenotypes. EMT-UC like cells were mainly enriched in UC tissues from patients with adverse prognosis and exhibited significantly elevated EMT, migration and gemcitabine tolerance in vitro. However, EMT-UC was not specifically identified from tumorous tissues, certain proportion of them were also identified in adjacent normal tissues. Tumorous EMT-UC highly expressed genes involved in malignant behaviors and exhibited adverse prognosis. Additionally, tumorous EMT-UC was associated with remodeled tumor microenvironment (TME), which exhibited high angiogenic and immunosuppressive potentials compared with the normal counterparts. Furthermore, a specific interaction of COL4A1 and ITGB1 was identified to be highly enriched in tumorous EMT-UC, and in the endothelial component. Targeting the interaction of COL4A1 and ITGB1 with specific antibodies significantly suppressed tumorous angiogenesis and alleviated gemcitabine resistance of UC. Overall, our findings demonstrated that the driven force of chemotherapy resistance and recurrence of UC was EMT-UC mediated COL4A1-ITGB1 interaction, providing a potential target for future UC treatment.

Juveniles, young adults, and infants with hepatitis B virus infection: A genomic study.

Integration of hepatitis B virus (HBV) DNA into the human genome is recognized as an oncogenic factor and a barrier to hepatitis B cure. In the study, biopsy liver tissues were collected from adolescents and young adults with acute HBV infection younger than or equal to 35 years of age and from HBV-infected infant patients younger than or equal to 6 months of age. A high-throughput sequencing method was used to detect HBV DNA integration. Totally, 12 adolescents, young adults, and 6 infants were included. Among the 12 patients with acute HBV infection, immunohistochemical staining of intrahepatic hepatitis B surface antigen for all displayed negative results, and no HBV DNA integrants in the hepatocyte DNA were confirmed. All infant patients had elevated levels of alanine aminotransferase and high levels of serum HBV DNA. Numerous gene sites of hepatocyte DNA were integrated by HBV DNA for each infant patient, ranging from 120 to 430 integration sites. The fragile histidine triad gene was the high-frequency integrated site in the intragenic region for infant patients. In conclusion, hepatocyte DNA is integrated by HBV DNA in babies with active hepatitis B but seems seldom affected among adolescents and young adults with acute HBV infection. Infantile hepatitis B should be taken seriously considering abundant HBV DNA integration events.

Multifunctional Fe-based coordination polymer nano-bomb modified with ß-lapachone and CaO2 for targeted tumor dual chemodynamic therapy with enhanced ferroptosis and H2O2 self-supply.

Chemodynamic therapy (CDT) is seriously limited by the inadequacy of exogenous catalytic ions and endogenous H2O2 in tumors. Herein, a multifunction nano-bomb integrated with calcium peroxide (CaO2) and ß-lapachone as donors of H2O2 and GSH-sensitive Fe-based coordination polymer as provider of catalytic ions was constructed for dual cascade-amplified tumor CDT. This hyaluronic acid (HA)-modified nano-bomb could be specially endocytosed by breast cancer cells through a targeting pathway, degraded and released cargoes in response to the GSH-rich cytoplasm. Furthermore, the released CaO2 and ß-lapachone could significantly self-generated sufficient H2O2, which could dual-cascade amplify CDT and induce severe oxidative to tumors via cooperating with the delivered iron ions from nano-bombs. Moreover, the unloaded iron and calcium ions could further accelerate tumor damage by overloading Ca2+ and ferroptosis, as accompanied by good magnetic resonance imaging (MRI). In vitro and in vivo studies collectively reveal that this nano-bomb not only self-initiates double cascade-amplified CDT via self-generation of H2O2, but also efficiently activates ferroptosis and initiates Ca2+ overloading, consequently significantly tumor growth suppression. This study offers a novel tumor-initiated nano-bomb for dual cascade-amplified CDT and bioimaging with activated ferroptosis and self-supplying H2O2.

Inquiry lipaseoring the mechanism of pancreatic lipase inhibition by isovitexin based on multispectral method and enzyme inhibition assay.

Isovitexin is a main natural flavonoid component in various plants. Currently, the inhibitory effect of isovitexin on pancreatic lipase (PL) and its mechanism have not been elucidated yet. In the present study, we investigated the inhibitory effect of isovitexin on PL, as well as its interaction mechanism, using enzyme inhibition methods, spectroscopic analysis, and molecular simulations. Results showed that isovitexin possessed significant PL inhibitory activity, with IC50 values of 0.26 ± 0.02 mM. The interaction between isovitexin and PL was dominated by static quenching, and mainly through hydrogen bonding and hydrophobic interaction forces. Analysis of fluorescence spectroscopy confirmed that isovitexin binding altered the conformation of the PL. Circular dichroism (CD) spectrum indicated that isovitexin altered the secondary structure of PL by decreasing the α-helix content and increasing the ß-fold content. Molecular simulations further characterize the conformational changes produced by the interaction between isovitexin with PL. The performed study may provide a new insight into the inhibitory mechanism of isovitexin as a novel PL inhibitor.

Hypoxia induces alterations in tRNA modifications involved in translational control.

BACKGROUND: Adaptation to high-altitude hypobaric hypoxia has been shown to require a set of physiological traits enabled by an associated set of genetic modifications, as well as transcriptome regulation. These lead to both lifetime adaptation of individuals to hypoxia at high altitudes and generational evolution of populations as seen for instance in those of Tibet. Additionally, RNA modifications, which are sensitive to environmental exposure, have been shown to play pivotal biological roles in maintaining the physiological functions of organs. However, the dynamic RNA modification landscape and related molecular mechanisms in mouse tissues under hypobaric hypoxia exposure remain to be fully understood. Here, we explore the tissue-specific distribution pattern of multiple RNA modifications across mouse tissues. RESULTS: By applying an LC-MS/MS-dependent RNA modification detection platform, we identified the distribution of multiple RNA modifications in total RNA, tRNA-enriched fragments, and 17-50-nt sncRNAs across mouse tissues; these patterns were associated with the expression levels of RNA modification modifiers in different tissues. Moreover, the tissue-specific abundance of RNA modifications was sensitively altered across different RNA groups in a simulated high-altitude (over 5500 m) hypobaric hypoxia mouse model with the activation of the hypoxia response in mouse peripheral blood and multiple tissues. RNase digestion experiments revealed that the alteration of RNA modification abundance under hypoxia exposure impacted the molecular stability of tissue total tRNA-enriched fragments and isolated individual tRNAs, such as tRNAAla, tRNAval, tRNAGlu, and tRNALeu. In vitro transfection experiments showed that the transfection of testis total tRNA-enriched fragments from the hypoxia group into GC-2spd cells attenuated the cell proliferation rate and led to a reduction in overall nascent protein synthesis in cells. CONCLUSIONS: Our results reveal that the abundance of RNA modifications for different classes of RNAs under physiological conditions is tissue-specific and responds to hypobaric hypoxia exposure in a tissue-specific manner. Mechanistically, the dysregulation of tRNA modifications under hypobaric hypoxia attenuated the cell proliferation rate, facilitated the sensitivity of tRNA to RNases, and led to a reduction in overall nascent protein synthesis, suggesting an active role of tRNA epitranscriptome alteration in the adaptive response to environmental hypoxia exposure.

Detachable MOF-Based Core/Shell Nanoreactor for Cancer Dual-Starvation Therapy With Reversing Glucose and Glutamine Metabolisms.

Tumor-dependent glucose and glutamine metabolisms are essential for maintaining survival, while the accordingly metabolic suppressive therapy is limited by the compensatory metabolism and inefficient delivery efficiency. Herein, a functional metal-organic framework (MOF)-based nanosystem composed of the weakly acidic tumor microenvironment-activated detachable shell and reactive oxygen species (ROS)-responsive disassembled MOF nanoreactor core is designed to co-load glycolysis and glutamine metabolism inhibitors glucose oxidase (GOD) and bis-2-(5-phenylacetmido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES) for tumor dual-starvation therapy. The nanosystem excitingly improves tumor penetration and cellular uptake efficiency via integrating the pH-responsive size reduction and charge reversal and ROS-sensitive MOF disintegration and drug release strategy. Furthermore, the degradation of MOF and cargoes release can be self-amplified via additional self-generation H2 O2 mediated by GOD. Last, the released GOD and BPTES collaboratively cut off the energy supply of tumors and induce significant mitochondrial damage and cell cycle arrest via simultaneous restriction of glycolysis and compensatory glutamine metabolism pathways, consequently realizing the remarkable triple negative breast cancer killing effect in vivo with good biosafety via the dual starvation therapy.

Hepatocyte proliferation favours viral clearance in young children with chronic hepatitis B virus infection.

AIM: The aim of this study is to explore the correlation between hepatocyte proliferation and hepatitis B virus (HBV) clearance in young children with chronic HBV infection. METHODS: We collected liver biopsy samples and clinical data corresponding to paediatric patients with chronic HBV infection. Ki-67 expression in liver tissues was evaluated by immunohistochemical staining. RESULTS: Eighteen patients were included and were divided into two groups based on different antiviral outcomes. Group I achieved hepatitis B surface antigen (HBsAg) loss within 48 weeks. Group II did not develop seroconversion from hepatitis B e (HBe) antigen to anti-HBe after 48 weeks. There were 10 patients in Group I and 8 in Group II, respectively. Demographical data and baseline virological and biochemical characteristics in serum across Group I and Group II were not statistically different. Histologically, mean Ki-67 expression index in Group I was 15%, while the mean index in Group II was 5%. There was a significant difference between the two groups (p < 0.01). CONCLUSION: High Ki-67 expression can contribute to viral clearance in young children with chronic HBV infection. This is the first confirmation of the association between hepatocyte proliferation and HBV clearance in vivo and has implications for novel therapeutic strategies against hepatitis B.

Design, Synthesis, and Biological Evaluation of mTOR-Targeting PROTACs Based on MLN0128 and Pomalidomide.

Mechanistic target of rapamycin (mTOR) is an effective anti-tumor drug target. Several mTOR kinase inhibitors have entered clinical research, but there are still challenges of potential toxicity. As a new type of targeted drug, proteolysis targeting chimeras (PROTACs) have features of low dosage and low toxicity. However, this approach has been rarely reported to involve mTOR degradation. In this study, the mTOR kinase inhibitor MLN0128 was used as the ligand to the protein of interest and conjugated with pomalidomide by diverse intermediate linkage chains. Several potential small molecule PROTACs for the degradation of mTOR were designed and synthesized. PROTAC compounds exhibited mTOR inhibitory activity and suppressed MCF-7 cell proliferation. The representative compound P1 could inhibit the expression of mTOR downstream proteins and the growth of cancer cells by inducing autophagy but not affecting the cell cycle and not inducing apoptosis.

Detection, Verification and Analysis of Micro Surface Defects in Steel Filament Using Eddy Current Principles, Scanning Electron Microscopy and Energy-Dispersive Spectroscopy.

In the current industrial revolution, advanced technologies and methods can be effectively utilized for the detection and verification of defects in high-speed steel filament production. This paper introduces an innovative methodology for the precise detection and verification of micro surface defects found in steel filaments through the application of the Eddy current principle. Permanent magnets are employed to generate a magnetic field with a high frequency surrounding a coil of sensors positioned at the filament's output end. The sensor's capacity to detect defects is validated through a meticulous rewinding process, followed by a thorough analysis involving scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS). Artificial defects were intentionally introduced into a sample, and their amplitudes were monitored to establish a threshold value. The amplitude signal of these created defect was identified at approximately 10% FSH, which corresponds to a crack depth of about 20 µm. In the experimental production of 182 samples covering 38 km, the defect ratio was notably high, standing at 26.37%. These defects appeared randomly along the length of the samples. The verification results underscore the exceptional precision achieved in the detection of micro surface defects within steel filaments. These defects were primarily characterized by longitudinal scratches and inclusions containing physical tungsten carbide.

Transcriptome and miRNAs Profiles Reveal Regulatory Network and Key Regulators of Secondary Xylem Formation in "84K" Poplar.

Secondary xylem produced by stem secondary growth is the main source of tree biomass and possesses great economic and ecological value in papermaking, construction, biofuels, and the global carbon cycle. The secondary xylem formation is a complex developmental process, and the underlying regulatory networks and potential mechanisms are still under exploration. In this study, using hybrid poplar (Populus alba × Populus glandulosa clone 84K) as a model system, we first ascertained three representative stages of stem secondary growth and then investigated the regulatory network of secondary xylem formation by joint analysis of transcriptome and miRNAs. Notably, 7507 differentially expressed genes (DEGs) and 55 differentially expressed miRNAs (DEMs) were identified from stage 1 without initiating secondary growth to stage 2 with just initiating secondary growth, which was much more than those identified from stage 2 to stage 3 with obvious secondary growth. DEGs encoding transcription factors and lignin biosynthetic enzymes and those associated with plant hormones were found to participate in the secondary xylem formation. MiRNA-target analysis revealed that a total of 85 DEMs were predicted to have 2948 putative targets. Among them, PagmiR396d-PagGRFs, PagmiR395c-PagGA2ox1/PagLHW/PagSULTR2/PagPolyubiquitin 1, PagmiR482d-PagLAC4, PagmiR167e-PagbHLH62, and PagmiR167f/g/h-PagbHLH110 modules were involved in the regulating cambial activity and its differentiation into secondary xylem, cell expansion, secondary cell wall deposition, and programmed cell death. Our results give new insights into the regulatory network and mechanism of secondary xylem formation.

Pharmacodynamics, Pharmacokinetics, and Kidney Distribution of Raw and Wine-Steamed Ligustri Lucidi Fructus Extracts in Diabetic Nephropathy Rats.

The purpose of this study was to investigate differences in the pharmacodynamic, pharmacokinetic, and kidney distribution between Ligustri Lucidi Fructus (LLF) and wine-steamed Ligustri Lucidi Fructus (WLL) extracts in diabetic nephropathy (DN) rats. The DN rats were induced by high-fat-sugar diet (HFSD)/streptozotocin (STZ) regimen. For pharmacodynamics, the DN rats were treated with LLF and WLL extracts to assess the anti-diabetic nephropathy effects. For pharmacokinetics and kidney distribution, the concentrations of drugs (hydroxytyrosol, salidroside, nuezhenidic acid, oleoside-11-methyl ester, specnuezhenide, 1‴-O-ß-d-glucosylformoside, G13, and oleonuezhenide) were determined. Regarding the pharmacodynamics, LLF and WLL extracts decreased the levels of blood glucose, serum creatinine (SCr), blood urea nitrogen (BUN), and 24-h urinary protein (24-h Upro) in DN rats. Furthermore, LLF and WLL extracts increased the level of high-density lipoprotein cholesterol (HDL-C); decreased the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C); and reduced levels of pro-inflammatory cytokines (IL-1ß, TNF-α, and IL-6) in DN rats. The anti-diabetic nephropathy effect of the WLL extract was better than that of the LLF extract. Regarding the pharmacokinetic and kidney tissue distribution, there were obvious differences in the eight ingredients between LLF and WLL extracts in DN rats. LLF and WLL extracts had protective effects on DN rats, while the WLL extract was better than the LLF extract regarding anti-diabetic nephropathy effects. The pharmacokinetic parameters and kidney distribution showed that wine-steaming could affect the absorption and distribution of the eight ingredients. The results provided a reasonable basis for the study of the clinical application and processing mechanism of LLF.

Preparation of Molecularly Imprinted Cysteine Modified Zinc Sulfide Quantum Dots Based Sensor for Rapid Detection of Dopamine Hydrochloride.

By combining surface molecular imprinting technology with cysteine-modified ZnS quantum dots, an elegant, molecularly imprinted cysteine-modified Mn2+: ZnS QDs (MIP@ZnS QDs) based fluorescence sensor was successfully developed. The constructed fluorescence sensor is based on a molecularly imprinted polymer (MIP) coated on the surface cysteine-modified ZnS quantum dots and used for rapid fluorescence detection of dopamine hydrochloride. The MIP@ZnS quantum dots possess the advantages of rapid response, high sensitivity, and selectivity for the detection of dopamine hydrochloride molecules. Experimental results show that the adsorption equilibrium time of MIP@ZnS QDs for dopamine hydrochloride molecules is 12 min, and it can selectively capture and bind dopamine in the sample with an imprinting factor of 29.5. The fluorescence quenching of MIP@ZnS QDs has a good linear (R2 = 0.9936) with the concentration of dopamine hydrochloride ranged from 0.01 to 1.0 µM, and the limit of detection is 3.6 nM. In addition, The MIP@ZnS QDs demonstrate good recyclability and stability and are successfully employed for detection of dopamine hydrochloride in urine samples with recoveries was 95.2% to 103.8%. The proposed MIP@ZnS QDs based fluorescent sensor provides a promising approach for food safety detection and drug analysis.

Adsorption of norfloxacin from wastewater by biochar with different substrates.

The type of feedstock and pyrolysis temperature are the main reasons affecting the properties of the resulting biochar. Therefore, this paper investigates the effects of different feedstocks (peanut shell, corn straw and soybean straw) and different pyrolysis temperatures (300, 450 and 600 â„ƒ) on the structural morphology and elemental composition of the resulting biochar. The optimum pyrolysis temperature of 600 â„ƒ was selected based on the comparison of the adsorption of NFX (norfloxacin) by the biochar prepared at different temperatures. Characterization of biochar materials using x-ray diffractometer, fourier transform infrared spectrometer and scanning electron microscope to study the changes in the physicochemical and structural properties of biochar. The results showed that the pH, surface area and ash content of biochar are increased with increasing temperature. The results of isothermal adsorption and adsorption kinetics experiments showed that the adsorption processes of the three biochar species on NFX were consistent with the Langmuir model and Pseudo-second order kinetic model. The adsorption process occurred in the surface layer of the biochar and was dominated by chemisorption. The inhibition of the adsorption of NFX was more obvious with the higher valence state of cations and the higher ion concentration. The adsorption mechanism of biochar on NFX includes pore filling, hydrogen bonding and electrostatic interactions.

Carbonic anhydrase and soluble adenylate cyclase regulation of cystic fibrosis cellular phenotypes.

Several aspects of the cell biology of cystic fibrosis (CF) epithelial cells are altered including impaired lipid regulation, disrupted intracellular transport, and impaired microtubule regulation. It is unclear how the loss of cystic fibrosis transmembrane conductance regulator (CFTR) function leads to these differences. It is hypothesized that the loss of CFTR function leads to altered regulation of carbonic anhydrase (CA) activity resulting in cellular phenotypic changes. In this study, it is demonstrated that CA2 protein expression is reduced in CF model cells, primary mouse nasal epithelial (MNE) cells, excised MNE tissue, and primary human nasal epithelial cells (P < 0.05). This corresponds to a decrease in CA2 RNA expression measured by qPCR as well as an overall reduction in CA activity in primary CF MNEs. The addition of CFTR-inhibitor-172 to WT MNE cells for ≥24 h mimics the significantly lower protein expression of CA2 in CF cells. Treatment of CF cells with l-phenylalanine (L-Phe), an activator of CA activity, restores endosomal transport through an effect on microtubule regulation in a manner dependent on soluble adenylate cyclase (sAC). This effect can be blocked with the CA2-selective inhibitor dorzolamide. These data suggest that the loss of CFTR function leads to the decreased expression of CA2 resulting in the downstream cell signaling alterations observed in CF.

Differential seedling growth and tolerance indices reflect drought tolerance in cotton.

BACKGROUND: Cotton production is adversely effected by drought stress. It is exposed to drought stress at various critical growth stages grown under a water scarcity environment. Roots are the sensors of plants; they detect osmotic stress under drought stress and play an important role in plant drought tolerance mechanisms. The seedling stage is very sensitive to drought stress, and it needed to explore the methods and plant characteristics that contribute to drought tolerance in cotton. RESULTS: Initially, seedlings of 18 genotypes from three Gossypium species: G. hirsutum, G. barbadense, and G. arboreum, were evaluated for various seedling traits under control (NS) and drought stress (DS). Afterward, six genotypes, including two of each species, one tolerant and one susceptible, were identified based on the cumulative drought sensitivity response index (CDSRI). Finally, growth rates (GR) were examined for shoot and root growth parameters under control and DS in experimental hydroponic conditions. A significant variation of drought stress responses was observed across tested genotypes and species. CDSRI allowed here to identify the drought-sensitive and drought-resistant cultivar of each investigated species. Association among root and shoots growth traits disclosed influential effects of enduring the growth under DS. The traits including root length, volume, and root number were the best indicators with significantly higher differential responses in the tolerant genotypes. These root growth traits, coupled with the accumulation of photosynthates and proline, were also the key indicators of the resistance to drought stress. CONCLUSION: Tolerant genotypes have advanced growth rates and the capacity to cop with drought stress by encouraging characteristics, including root differential growth traits coupled with physiological traits such as chlorophyll and proline contents. Tolerant and elite genotypes of G. hirsutum were more tolerant of drought stress than obsolete genotypes of G. barbadense and G. arboreum. Identified genotypes have a strong genetic basis of drought tolerance, which can be used in cotton breeding programs.

A new NLR gene for resistance to Tomato spotted wilt virus in tomato (Solanum lycopersicum).

KEY MESSAGE: A typical NLR gene, Sl5R-1, which regulates Tomato spotted wilt virus resistance, was fine mapped to a region less than 145 kb in the tomato genome. Tomato spotted wilt is a viral disease caused by Tomato spotted wilt virus (TSWV), which is a devastating disease that affects tomato (Solanum lycopersicum) production worldwide, and the resistance provided by the Sw-5 gene has broken down in some cases. In order to identify additional genes that confer resistance to TSWV, the F2 population was mapped using susceptible (M82) and resistant (H149) tomato lines. After 3 years of mapping, the main quantitative trait locus on chromosome 05 was narrowed to a genomic region of 145 kb and was subsequently identified by the F2 population, with 1971 plants in 2020. This region encompassed 14 candidate genes, and in it was found a gene cluster consisting of three genes (Sl5R-1, Sl5R-2, and Sl5R-3) that code for NBS-LRR proteins. The qRT-PCR and virus-induced gene silencing approach results confirmed that Sl5R-1 is a functional resistance gene for TSWV. Analysis of the Sl5R-1 promoter region revealed that there is a SlTGA9 transcription factor binding site caused by a base deletion in resistant plants, and its expression level was significantly up-regulated in infected resistant plants. Analysis of salicylic acid (SA) and jasmonic acid (JA) levels and the expression of SA- and JA-regulated genes suggest that SlTGA9 interacts or positively regulates Sl5R-1 to affect the SA- and JA-signaling pathways to resist TSWV. These results demonstrate that the identified Sl5R-1 gene regulates TSWV resistance by its own promoter interacting with the transcription factor SlTGA9.

Perampanel add-on therapy for drug-refractory epilepsy: A single-center retrospective study based on 6-month treatment outcomes in Central China.

OBJECTIVE: To systematically evaluate the efficacy, tolerability and retention of perampanel (PER) for treating drug-refractory epilepsy (DRE), and to investigate the independent factors affecting efficacy and retention. We hope this will provide clinicians with guidelines for the use of PER to treat patients with DRE. METHODS: We conducted a single-center retrospective observational study of patients with DRE who received PER as add-on therapy at the Epilepsy Center of the People's Hospital of Henan Province, China, between 2020 Mar. and 2021 Sep. We collected clinical data from these patients. The observation period was 6 months. The observation endpoint is the drug response and retention rate at 6 months of PER use. Regression analyses were used to compare the differences in efficacy and retention rates, respectively. RESULTS: Clinical data were obtained for 72 patients with DRE (mean duration of treatment: 10.6 months). At 6 months, 25% of patients (n = 18) were seizure free; 18.1% of patients (n = 13) remained seizure free for 6 months after the addition of PER. 22.2% of patients (n = 16) had a response (One of the patients was withdrawn 5 months after adding PER due to financial difficulties). The retention rate of PER at 6 months was 77.8%. Adverse effects tended to be dominated by neuropsychiatric symptoms. Multifactorial logistic regression analysis showed significant differences in whether the baseline seizure frequency exceeded 4 seizures/month (OR = 0.232, 95%CI: 0.077-0.702, p = 0.01) and whether the number of previously failed ASMs exceeded 3 (OR = 0.316; 95%CI:0.109-0.920, p = 0.035). This indicates that the risk of experiencing a nonresponse is higher with a higher baseline seizure frequency as well as with a higher number of previous ASM failures. Therefore, a baseline frequency exceeding four seizures/month and more than three previous ASM failures were independent influencing factors for PER addition treatment for patients with DRE. Multifactorial COX regression showed that patients with DRE due to infection had a lower retention rate (OR = 15.957, 95% CI: 3.692-68.972, P < 0.001) than patients with DRE due to other noninfectious etiologies. Patients with DRE who only had a single seizure type (OR = 0.053, 95% CI:0.006-0.476, P = 0.009), and patients who did not have cognitive impairment (OR = 134.253, 95% CI:5.623-3205.104, P = 0.002) showed longer durations of PER use. Infection-related epilepsy etiology, experiencing multiple types of seizures, and with cognitive impairment were independent influencing factors on PER use retention in patients with DRE. CONCLUSION: Our study demonstrated the efficacy of PER for reducing seizure frequency in patients with DRE and found significant differences in efficacy and retention rate, respectively. This provides a basis for assessing the expected efficacy and duration of use of PER for patients with DRE.

AlepPBP2, but not AlepPBP3, may involve in the recognition of sex pheromones and maize volatiles in Athetis lepigone.

Athetis lepigone Möschler (Lepidoptera, Noctuidae) is a common maize pest in Europe and Asia. However, there is no long-term effective management strategy is available yet to suppress its population. Adults rely heavily on olfactory cues to locate their optimal host plants and oviposition sites. Pheromone-binding proteins (PBPs) are believed to be responsible for recognizing and transporting different odorant molecules to interact with receptor membrane proteins. In this study, the ligand-binding specificities of two AlepPBPs (AlepPBP2 and AlepPBP3) for sex pheromone components and host plant (maize) volatiles were measured by fluorescence ligand-binding assay. The results demonstrated that AlepPBP2 had a high affinity with two pheromones [(Z)-7-dodecenyl acetate, Ki = 1.11 ± 0.1 µM, (Z)-9-tetradecenyl acetate, Ki = 1.32 ± 0.15 µM] and ten plant volatiles, including (-)-limonene, α-pinene, myrcene, linalool, benzaldehyde, nonanal, 2-hexanone, 3-hexanone, 2-heptanone and 6-methyl-5-hepten-2-one. In contrast, we found that none of these chemicals could bind to AlepPBP3. Our results clearly show no significant differences in the functional characterization of the binding properties between AlepPBP2 and AlepPBP3 to sex pheromones and host plant volatiles. Furthermore, molecular docking was employed for further detail on some crucial amino acid residues involved in the ligand-binding of AlepPBP2. These findings will provide valuable information about the potential protein binding sites necessary for protein-ligand interactions which appear as attractive targets for the development of novel technologies and management strategies for insect pests.