Unraveling the Binding Mode of Cyclic Adenosine-Inosine Monophosphate (cAIMP) to STING through Molecular Dynamics Simulations.

The stimulator of interferon genes (STING) plays a significant role in immune defense and protection against tumor proliferation. Many cyclic dinucleotide (CDN) analogues have been reported to regulate its activity, but the dynamic process involved when the ligands activate STING remains unclear. In this work, all-atom molecular dynamics simulations were performed to explore the binding mode between human STING (hSTING) and four cyclic adenosine-inosine monophosphate analogs (cAIMPs), as well as 2',3'-cGMP-AMP (2',3'-cGAMP). The results indicate that these cAIMPs adopt a U-shaped configuration within the binding pocket, forming extensive non-covalent interaction networks with hSTING. These interactions play a significant role in augmenting the binding, particularly in interactions with Tyr167, Arg238, Thr263, and Thr267. Additionally, the presence of hydrophobic interactions between the ligand and the receptor further contributes to the overall stability of the binding. In this work, the conformational changes in hSTING upon binding these cAIMPs were also studied and a significant tendency for hSTING to shift from open to closed state was observed after binding some of the cAIMP ligands.

Lysine-Specific Demethylase 1 Inhibitors: A Comprehensive Review Utilizing Computer-Aided Drug Design Technologies.

Lysine-specific demethylase 1 (LSD1/KDM1A) has emerged as a promising therapeutic target for treating various cancers (such as breast cancer, liver cancer, etc.) and other diseases (blood diseases, cardiovascular diseases, etc.), owing to its observed overexpression, thereby presenting significant opportunities in drug development. Since its discovery in 2004, extensive research has been conducted on LSD1 inhibitors, with notable contributions from computational approaches. This review systematically summarizes LSD1 inhibitors investigated through computer-aided drug design (CADD) technologies since 2010, showcasing a diverse range of chemical scaffolds, including phenelzine derivatives, tranylcypromine (abbreviated as TCP or 2-PCPA) derivatives, nitrogen-containing heterocyclic (pyridine, pyrimidine, azole, thieno[3,2-b]pyrrole, indole, quinoline and benzoxazole) derivatives, natural products (including sanguinarine, phenolic compounds and resveratrol derivatives, flavonoids and other natural products) and others (including thiourea compounds, Fenoldopam and Raloxifene, (4-cyanophenyl)glycine derivatives, propargylamine and benzohydrazide derivatives and inhibitors discovered through AI techniques). Computational techniques, such as virtual screening, molecular docking and 3D-QSAR models, have played a pivotal role in elucidating the interactions between these inhibitors and LSD1. Moreover, the integration of cutting-edge technologies such as artificial intelligence holds promise in facilitating the discovery of novel LSD1 inhibitors. The comprehensive insights presented in this review aim to provide valuable information for advancing further research on LSD1 inhibitors.

Goethite adaptation prompts alterations in antibiotic susceptibility and suppresses development of antibiotic resistance in bacteria.

Understanding the impact of environmental factors on antibiotic sensitivity and the emergence of antibiotic resistance in microorganism is crucial for antibiotics management and environmental risk assessment. Natural materials, like mineral particles, are prevalent in aquatic and terrestrial ecosystems. However, it remains unclear how microorganism adapt to the physical stress of mineral particles and whether this adaptation influences antibiotic sensitivity and the evolution of antibiotic resistance. In this study, the model bacterium Escherichia coli (E. coli) was exposed to the mineral particle goethite for 30 generations. Adaptive morphogenesis, including an increase in the fraction of spherical bacteria, variations in bacterial mobility, a slightly increased cell membrane thickness, and genome-wide changes in the transcriptomic profile, were observed in adapted E. coli samples to counteract the stress. Moreover, the goethite adapted E. coli showed increased susceptibility to antibiotics including amoxicillin and tetracycline, and decreased susceptibility to kanamycin compared to its ancestral counterparts. These alterations in antibiotic susceptibility in the adapted E. coli were not heritable, as evidenced by the gradual recovery of antibiotic tolerance in cells with the cessation of goethite exposure. Transcriptomic data and a series of experiments suggested that these changes may be associated with variations in cell membrane property and iron metabolism. In addition, the evolution of antibiotic resistance in adapted cells occurred at a slower rate compared to their ancestral counterparts. For instance, E. coli adapted to goethite at a concentration of 1 mg/mL did not acquire antibiotic resistance even after 13 generations, probably due to its poor biofilm-formation capacity. Our findings underscore the occurrence of microbial adaptation to goethite, which influenced antibiotic sensitivity and decelerated the development of resistance in microorganisms. This insight contributes to our comprehension of the natural dynamics surrounding the evolution of antibiotic resistance and opens new perspectives for addressing this issue through nanotechnology-based approaches.

S100A16 cooperates with DEPDC1 to promote the progression and angiogenesis of nephroblastoma through PI3K/Akt/mTOR pathway.

S100 calcium-binding protein A16 (S100A16) has previously been reported to play a role in tumor cells. Nevertheless, the role that S100A16 played in nephroblastoma cells remains obscure. The expression of S100A16 and DEPDC1 were detected via RT-q PCR and western blotting. Cell transfection was performed to overexpress DEPDC1 or interfere S100A16. CCK8 was applied for the assessment of cell viability. The apoptotic level and the capabilities of WiT49 cells to proliferate, invade and migrated were appraised utilizing Tunel, colony formation Transwell, and wound healing, separately. The angiogenesis was estimated through tube formation assay. Co-immunoprecipitation (CO-IP) was performed to examine the targeted binding of S100A16 to DEPDC1. The contents of PI3K/Akt/mTOR pathway-related proteins were resolved by virtue of western blot. S100A16 and DEPDC1 expression levels were significantly increased in nephroblastoma cell lines. S100A16 deletion suppressed nephroblastoma cell proliferative, invasive, migrative and angiogenetic capabilities but facilitated the apoptotic level. Moreover, S100A16 could bind DEPDC1, DEPDC1 overexpression partially reversed the inhibitory effect of S100A16 interference on nephroblastoma cell. DEPDC1 overexpression also partially counteracted the suppressive impacts of S100A16 interference on PI3K/Akt/mTOR pathway-related proteins. S100A16 synergistic with DEPDC1 promotes the progression and angiogenesis of nephroblastoma cell through the PI3K/Akt/mTOR pathway.

Regioselective synthesis of indazolo[2,3-a]quinazolines enabled by I2/S-facilitated annulation relay dehydrogenative aromatization of cyclohexanones.

A method for concise and efficient synthesis of indazolo[2,3-a]quinazolines has been developed via a sequential annulation of 3-aminoindazoles and dehydrogenative aromatization of cyclohexanones. This high regioselectivity is attributed to the fact that the Mannich reaction is superior to the aldol reaction in this system. It is worth mentioning that this convenient process is successfully extended to 3-aminopyrazoles for assembling another class of medicinally prevalent pyrazolo[1,5-a]quinazolines.

Sustainable production of Fe-doped MnO2 nanoparticles for accelerated tetracycline antibiotic detoxification.

Manganese dioxide (MnO2) has been recognized as one of the natural systems' most active mineral oxidants. However, when it comes to catalytic oxidation of antibiotic applications, pure MnO2 falls short in delivering satisfactory performance. Hence, a set of Fe3+-doped porous MnO2 (0.02Fe-MnO2, 0.1Fe-MnO2, and 0.14Fe-MnO2) nanoparticles were synthesized here via a convenient and energy-efficient one-step reaction method. A series of experiments revealed that Fe-doping strategy enhances the properties of MnO2 host by suppressing the crystalline structure, increasing the amount of surface oxygen defects, and modifying the Mn3+/Mn4+ ratio. Specifically, the tetracycline (TC) removal efficiency of 0.14Fe-MnO2 reaches 92% without the need for any additional co-oxidant, representing a 20% improvement over pristine MnO2 nanoparticles. Moreover, this process shows a fast dynamic (achieving 70% of TC removal in just 5 min) and demonstrates pH-resistance, maintaining high TC removal efficiency (≥90%) over a wide pH range of 3.0-9.0. Mechanical studies reveal that the degradation of TC can be attributed to the oxidation by reactive oxygen radicals and Mn3+, with 1O2 being the primary radical involved in the reaction, accounting for 55% of TC removal. Importantly, cytotoxicity testing indicates that the biotoxicity of TC toward organisms can be effectively mitigated using 0.14Fe-MnO2 nanomaterial. This study presents a readily applicable candidate for economically and conveniently eliminating of environmental TC pollution, thereby reducing the threat posed by TC pollution to the ecosystem.

High-performance Vo-ZnO/ZnS benefiting nanoarchitectonics from the synergism between defect engineering and surface engineering for photoelectrochemical glucose sensors.

In this study, a ZnO/ZnS nanocluster heterojunction photoelectrode rich in surface oxygen defects (Vo-ZnO/ZnS) was prepared by applying a simple in situ anion substitution and nitrogen atmosphere annealing method. The synergism between defect and surface engineering significantly improved the photocatalysts. Given this synergism, Vo-ZnO/ZnS was endowed with a long carrier lifetime, narrow band gap, high carrier density, and high performance toward electron transfer under light conditions. Thus, Vo-ZnO/ZnS had three times the photocurrent density of ZnO under light illumination. To further evaluate its advantages in the field of photoelectric bioassay, Vo-ZnO/ZnS was applied as the photocathode of photoelectric sensor system for glucose detection. Vo-ZnO/ZnS showed excellent performance in glucose detection in various aspects, including a low detection limit, high detection sensitivity, and a wide detection range.

Study on the Effect of Bushen Zhuanggu Tablet Combined with Conventional Regimen on Bone Mineral Density Improvement, Functional Recovery and Fracture Risk Prevention in Patients with Postmenopausal Osteoporosis.

Objective: This case-control study was to explore the effect of Bushen Zhuanggu tablet combined with routine regimen on bone mineral density (BMD) improvement, functional recovery, and fracture prevention in postmenopausal osteoporosis (PMOP) patients. Methods: 180 postmenopausal osteoporosis patients were randomly selected from communities A, B, and C cohorts as research subjects from January to May 2021. The study subjects were divided into three groups. The groups were in a 1 : 1 ratio according to the principles of nonrandomised, concurrent controlled trials, and methods. There were 60 participants in each group (group A, group B, and group C). Group A was treated with Bushen Zhuanggu tablet for antiosteoporosis + basic treatment (calcium supplement and vitamin D). Group C was given Bushen Zhuanggu tablet for antiosteoporosis intervention. Group B was given basic treatment (calcium supplement and vitamin D supplementation) as a control group. The follow-up time was 6 months after treatment. Finally, we compare the differences in calcium and phosphorus metabolism indexes, BMD, bone metabolism indexes, upper and lower limb muscle strength, and quality of life scores. Results: Group A, B, and C's effective rate was 98.33%, 80.00%, and 93.33%, respectively. The group A's effective rate was significantly higher than that in group B and C, and the difference was statistically significant (P < 0.05). After 6 months intervention, the levels of serum Ca2+, serum phosphorus (P), serum creatinine (Cr), and parathyroid hormone (PTH) in 3 groups decreased. Ca, P, Scr, and PTH levels in group A were the lowest among study groups, and the difference was statistically significant (P < 0.05). The increase in the BMD of lumbar spine, the left femoral neck, and Ward's triangle area of the three groups were observed with the highest data in group A. After 6 months of treatment, the levels of serum N-terminal propeptide of type I procollagen, PINP, and serum osteocalcin (OC) increased, while the levels of ß-cross-linked C-terminal telopeptide of type I collagen (ß-CTX) and alkaline phosphatase (ALP) decreased in the three groups. The improvement of all bone metabolic indexes in group A was significantly better than that in B and C groups, and the difference was statistically significant (P < 0.05). The enhanced upper limb muscle strength and the shorter standing-walking timing test (TUGT) time were observed after 6 months of treatment. The improvement effect of upper and lower limb muscle strength in group A was significantly better than that in B and C groups, and the difference was statistically significant (P < 0.05). There were significant differences in physiological function, life function, general health status, physical pain, mental state, emotional function, vitality, and social function among the three groups after 6 months treatment, and the difference was statistically significant (P < 0.05). The score of quality of life in group A was higher than that in B and C groups, and the difference was statistically significant (P < 0.05). Conclusion: Bushen Zhuanggu tablet combined with conventional therapy is effective in the postmenopausal osteoporosis treatment, which effectively increase the BMD, regulate calcium and phosphorus metabolism, promote the recovery of limb function, prevent the recurrence of fracture, and improve the patients' quality of life. This treatment scheme is worth popularizing.

Ultrasensitive and Rapid Visual Detection of Escherichia coli O157:H7 Based on RAA-CRISPR/Cas12a System.

Escherichia coli (E. coli) O157:H7 is a major foodborne and waterborne pathogen that can threaten human health. Due to its high toxicity at low concentrations, it is crucial to establish a time-saving and highly sensitive in situ detection method. Herein, we developed a rapid, ultrasensitive, and visualized method for detecting E. coli O157:H7 based on a combination of Recombinase-Aided Amplification (RAA) and CRISPR/Cas12a technology. The CRISPR/Cas12a-based system was pre-amplified using the RAA method, which showed high sensitivity and enabled detecting as low as ~1 CFU/mL (fluorescence method) and 1 × 102 CFU/mL (lateral flow assay) of E. coli O157:H7, which was much lower than the detection limit of the traditional real-time PCR technology (103 CFU/mL) and ELISA (104~107 CFU/mL). In addition, we demonstrated that this method still has good applicability in practical samples by simulating the detection in real milk and drinking water samples. Importantly, our RAA-CRISPR/Cas12a detection system could complete the overall process (including extraction, amplification, and detection) within 55 min under optimized conditions, which is faster than most other reported sensors, which take several hours to several days. The signal readout could also be visualized by fluorescence generated with a handheld UV lamp or a naked-eye-detected lateral flow assay depending on the DNA reporters used. Because of the advantages of being fast, having high sensitivity, and not requiring sophisticated equipment, this method has a promising application prospect for in situ detection of trace amounts of pathogens.

Diet composition and interspecific niche of Taohongling Sika deer (Cervusnipponkopschi) and its sympatric Reeve's muntjac (Muntiacusreevesi) and Chinese hare (Lepussinensis) in winter (Animalia, Mammalia).

Species co-existence depends on how organisms utilize their environment and resources. Little is known about the winter diet composition and sympatric co-existence of South China sika deer and its companion species in Taohongling. In this study, high-throughput sequencing and metabarcoding trnL were used to study the diet composition and interspecific relationship including sika deer, Reeve's muntjac, and Chinese hare. Our results show that 203 genera in 90 families are contained in the diet of sika deer, 203 genera in 95 families for Reeve's muntjac, and 163 genera in 75 families for Chinese hare. Sika deer fed on Rubuschingii, Loropetalumchinense, and Euryajaponica in winter, accounting for 75.30%; Reeve's muntjac consumed mainly R.chingii, E.japonica, and Euonymusgrandiflorus, accounting for 68.80%, and Chinese hare mainly fed on R.chingii, Smilaxchina, and Rhuschinensis, accounting for 41.98%. The Shannon index showed no significant difference between groups (p > 0.05). The NMDS analysis found considerable overlap among three species. Sika deer and Reeve's muntjac consumed similar forage plants but varied greatly in Chinese hare, which occupied the widest choice in winter, resulting in higher diet breadth and increased dietary divergence, thereby reducing competition and facilitating coexistence. The diet niche overlap index among them, as represented by Pianka's index, ranging from 0.62 between sika deer and Chinese hare to 0.83 between sika deer and Reeve's muntjac, which indicated a more similar niche and potential competition in closely related species. Our findings provide a new diet perspective of three herbivores, leading to a more comprehensive understanding of resource partitioning and species coexistence.

Discovery of novel, potent, and orally bioavailable HDACs inhibitors with LSD1 inhibitory activity for the treatment of solid tumors.

Histone deacetylases (HDACs) and lysine-specific demethylase 1 (LSD1) are attractive targets for epigenetic cancer therapy. There is an intimate interplay between the two enzymes. HDACs inhibitors have shown synergistic anticancer effects in combination with LSD1 inhibitors in several types of cancer. Herein, we describe the discovery of compound 5e, a highly potent HDACs inhibitor (HDAC1/2/6/8; IC50 = 2.07/4.71/2.40/107 nM) with anti-LSD1 potency (IC50 = 1.34 µM). Compound 5e exhibited marked antiproliferative activity in several cancer cell lines. 5e effectively induced mitochondrial apoptosis with G2/M phase arrest, inhibiting cell migration and invasion in MGC-803 and HCT-116 cancer cells. It also showed good liver microsomal stability and acceptable pharmacokinetic parameters in SD rats. More importantly, orally administered compound 5e demonstrated higher in vivo antitumor efficacy than SAHA in the MGC-803 (TGI = 71.5%) and HCT-116 (TGI = 57.6%) xenograft tumor models accompanied by good tolerability. This study provides a novel lead compound with dual inhibitory activity against HDACs and LSD1 to further develop epigenetic drugs for solid tumor therapy. Further optimization is needed to improve the LSD1 activity to achieve dual inhibitors with balanced potency on LSD1 and HDACs.

Differences in the luminal and mucosal gut microbiomes and metabolomes of oriental rat snake (Ptyas mucosus).

Previous studies regarding the gastrointestinal biogeography of microbiomes generally focused on longitudinal comparisons, whereas few studies have compared luminal and mucosal microbiomes. Investigations of the snake gut microbiome have attracted interest because of the unique digestive physiology and hibernation behavior, but adequate sampling methods must be developed. Here, we used an omics approach combining 16S rRNA gene sequencing with untargeted metabolomics to profile the luminal and mucosal gut microbiomes and metabolomes in oriental rat snakes, with the goal of revealing the heterogeneity and co-occurrence at these sites. The α-diversity of the gut microbiome was significantly higher at mucosal sites than at luminal sites. Microbial composition also differed according to sampling site, with significant differences in the abundances of dominant phyla and genera, as well as ß-diversity clustering and distribution. Metabolome profiling revealed differences that were mainly related to cholinergic substances and nucleic acids. Analysis of variations in Kyoto Encyclopedia of Genes and Genomes functions of microbes and metabolites showed that the mucosal microbiome was more frequently involved in genetic information processing and cellular processes, whereas the luminal microbiome generally participated in metabolic regulation. Notably, we found a greater abundance of the opportunistic pathogen genus Escherichia-Shigella at luminal sites and higher levels of the lipid-regulator metabolite fenfluramine at mucosal sites. Despite the extensive differences between the two sampling sites, the results revealed similarities in terms of amplicon sequence variant composition and dominant core microbes. This pilot exploration of luminal and mucosal microbiomes and metabolites provides key insights to guide future research. KEY POINTS: • Snake luminal and mucosal microbiota was distinct in composition and function. • Metabolome profiling revealed differences related to different metabolites. • The pathogenic microbes are more likely to colonize the gut lumina.

Causal link between prefrontal cortex and EEG microstates: evidence from patients with prefrontal lesion.

Introduction: At present, elucidating the cortical origin of EEG microstates is a research hotspot in the field of EEG. Previous studies have suggested that the prefrontal cortex is closely related to EEG microstate C and D, but whether there is a causal link between the prefrontal cortex and microstate C or D remains unclear. Methods: In this study, pretrial EEG data were collected from ten patients with prefrontal lesions (mainly located in inferior and middle frontal gyrus) and fourteen matched healthy controls, and EEG microstate analysis was applied. Results: Our results showed that four classical EEG microstate topographies were obtained in both groups, but microstate C topography in patient group was obviously abnormal. Compared to healthy controls, the average coverage and occurrence of microstate C significantly reduced. In addition, the transition probability from microstate A to C and from microstate B to C in patient group was significantly lower than those of healthy controls. Discussion: The above results demonstrated that the damage of prefrontal cortex especially inferior and middle frontal gyrus could lead to abnormalities in the spatial distribution and temporal dynamics of microstate C not D, showing that there is a causal link between the inferior and middle frontal gyrus and the microstate C. The significance of our findings lies in providing new evidence for elucidating the cortical origin of microstate C.

Design Two Novel Tetrahydroquinoline Derivatives against Anticancer Target LSD1 with 3D-QSAR Model and Molecular Simulation.

Lysine-specific demethylase 1 (LSD1) is a histone-modifying enzyme, which is a significant target for anticancer drug research. In this work, 40 reported tetrahydroquinoline-derivative inhibitors targeting LSD1 were studied to establish the three-dimensional quantitative structure-activity relationship (3D-QSAR). The established models CoMFA (Comparative Molecular Field Analysis (q2 = 0.778, Rpred2 = 0.709)) and CoMSIA (Comparative Molecular Similarity Index Analysis (q2 = 0.764, Rpred2 = 0.713)) yielded good statistical and predictive properties. Based on the corresponding contour maps, seven novel tetrahydroquinoline derivatives were designed. For more information, three of the compounds (D1, D4, and Z17) and the template molecule 18x were explored with molecular dynamics simulations, binding free energy calculations by MM/PBSA method as well as the ADME (absorption, distribution, metabolism, and excretion) prediction. The results suggested that D1, D4, and Z17 performed better than template molecule 18x due to the introduction of the amino and hydrophobic groups, especially for the D1 and D4, which will provide guidance for the design of LSD1 inhibitors.

A comprehensive review of BET-targeting PROTACs for cancer therapy.

Targeted protein degradation using proteolysis-targeting chimeras (PROTACs) has emerged as an effective strategy for drug discovery, given their unique advantages over target protein inhibition. The bromodomain and extra-terminal (BET) family proteins play a key role in regulating oncogene expression and are considered attractive therapeutic targets for cancer therapy. Considering the therapeutic potential of BET proteins in cancer and the marked attractiveness of PROTACs, BET-targeting PROTACs have been extensively pursued. Recently, BET-targeting PROTACs based on new E3 ligases and novel strategies, such as light-activated, macrocyclic, folate-caged, aptamer-PROTAC conjugation, antibody-coupling, and autophagy-targeting strategies, have emerged. In the present review, we provide a comprehensive summary of advances in BET-targeting PROTACs.

Gastrointestinal Biogeography of Luminal Microbiota and Short-Chain Fatty Acids in Sika Deer (Cervus nippon).

The gut microbiota of sika deer has been widely investigated, but the spatial distribution of symbiotic microbes among physical niches in the gastrointestinal tract remains to be established. While feces are the most commonly used biological samples in these studies, the accuracy of fecal matter as a proxy of the microbiome at other gastrointestinal sites is as yet unknown. In the present study, luminal contents obtained along the longitudinal axis of deer gastrointestinal tract (rumen, reticulum, omasum, abomasum, small intestine, cecum, colon, and rectum) were subjected to 16S rRNA gene sequencing for profiling of the microbial composition, and samples from the rumen, small intestine, and cecum were subjected to metabolomic analysis to evaluate short-chain fatty acid (SCFA) profiles. Prevotella bacteria were the dominant gastric core microbes, while Christensenellaceae_R-7_group was predominantly observed in the intestine. While the eight gastrointestinal sites displayed variations in microbial diversity, abundance, and function, they could be clustered into stomach, small intestine, and large intestine segments, and the results further highlighted a specific microbial niche of the small intestine. SCFA levels in the rumen, small intestine, and cecum were significantly different, with Bacteroidetes and Spirochaetes were shown to play a critical role in SCFA production. Finally, the rectal microbial composition was significantly correlated with colonic and cecum communities but not those of the small intestine and four gastric sites. Quantification of the compositions and biogeographic relationships between gut microbes and SCFAs in sika deer should provide valuable insights into the interactions contributing to microbial functions and metabolites. IMPORTANCE Feces or specific segments of the gastrointestinal tract (in particular, the rumen) were sampled to explore the gut microbiome. The gastrointestinal biogeography of the luminal microbiota in ruminants, which is critical to guide accurate sampling for different purposes, is poorly understood at present. The microbial community of the rectal sample (as a proxy of fecal sample) showed higher correlation with those of other large intestinal sites relative to the small intestine or stomach, suggesting that the microbial composition is specifically shaped by the unique physiological characteristics of different gastrointestinal niches. In addition, significant differences in microbiomes and SCFAs were observed among the different gastrointestinal sites.

EEG microstate in first-episode drug-naive adolescents with depression.

A growing number of studies have revealed significant abnormalities in electroencephalography (EEG) microstate in patients with depression, but these findings may be affected by medication. Therefore, how the EEG microstates abnormally change in patients with depression in the early stage and without the influence of medication has not been investigated so far. Resting-state EEG data and Hamilton Depression Rating Scale (HDRS) were collected from 34 first-episode drug-naïve adolescent with depression and 34 matched healthy controls. EEG microstate analysis was applied and nonlinear characteristics of EEG microstate sequences were studied by sample entropy and Lempel-Ziv complexity (LZC). The microstate temporal parameters and complexity were tried to train an SVM for classification of patients with depression. Four typical EEG microstate topographies were obtained in both groups, but microstate C topography was significantly abnormal in depression patients. The duration of microstate B, C, D and the occurrence and coverage of microstate B significantly increased, the occurrence and coverage of microstate A, C reduced significantly in depression group. Sample entropy and LZC in the depression group were abnormally increased and were negatively correlated with HDRS. When the combination of EEG microstate temporal parameters and complexity of microstate sequence was used to classify patients with depression from healthy controls, a classification accuracy of 90.9% was obtained. Abnormal EEG microstate has appeared in early depression, reflecting an underlying abnormality in configuring neural resources and transitions between distinct brain network states. EEG microstate can be used as a neurophysiological biomarker for early auxiliary diagnosis of depression.

FOXO3a­modulated DEPDC1 promotes malignant progression of nephroblastoma via the Wnt/ß­catenin signaling pathway.

DEP domain containing 1 (DEPDC1) and forkhead box transcription factor 3a (FOXO3a) serve a role in tumor cells. To the best of our knowledge, however, the expression of DEPDC1 and FOXO3a in nephroblastoma and their role and potential mechanisms in nephroblastoma cells have not been reported. The aim of the present study was to characterize the expression of DEPDC1 and FOXO3a in nephroblastoma, as well as the underlying mechanisms. The expression levels of DEPDC1 and FOXO3a were detected using reverse transcription­quantitative PCR and western blotting. Cell viability, proliferation, invasion and migration were detected using Cell Counting Kit­8, colony formation, Transwell and wound healing assays, respectively. The activity of DEPDC1 promoter was detected by dual­luciferase reporter assay and the association between FOXO3a and DEPDC1 was detected using immunoprecipitation. DEPDC1 expression was significantly increased in nephroblastoma cells, particularly WiT49 cells. Compared with the negative control, DEPDC1 knockdown significantly inhibited proliferation, invasion and migration of WiT49 cells, while DEPDC1 overexpression (Ov) reversed these effects. By contrast, expression of FOXO3a was decreased in WiT49 cells and immunoprecipitation showed that FOXO3a bound to the DEPDC1 promoter. Ov­FOXO3a inhibited WiT49 cell proliferation, invasion and migration, as well as protein expression levels of phosphorylated­glycogen synthase kinase­3ß, Wnt3a and ß­catenin, while DEPDC1 Ov reversed the inhibitory effects of FOXO3a Ov on WiT49 cells. In conclusion, DEPDC1 promoted malignant progression of nephroblastoma via the Wnt/ß­catenin signaling pathway; this may be regulated by FOXO3a.

Inception-LSTM Human Motion Recognition with Channel Attention Mechanism.

An improved channel attention mechanism Inception-LSTM human motion recognition algorithm for inertial sensor signals is proposed to address the problems of high cost, many blind areas, and susceptibility to environmental effects in traditional video image-oriented human motion recognition algorithms. The proposed algorithm takes the inertial sensor signal as input, first extracts the spatial features of the sensor signal into the feature vector graph from multiple scales using the Inception parallel convolution structure, then uses the improved ECA (Efficient Channel Attention) channel attention module to extract the critical details of the feature vector graph of the sensor data, and finally uses the LSTM network to further extract the temporal features of the inertial sensor signals to achieve the classification and recognition of human motion posture. The experiment results demonstrate that 95.04% recognition accuracy on the public dataset PAMAP2 and 98.81% accuracy on the self-built dataset can be realized based on the algorithm model, indicating that the algorithm model has a superior recognition effect. In addition, the results of the visual analysis of channel attention weights show that the proposed model is interpretable for the recognition of human motions and is consistent with the living intuition.

Construction of K and Tb Co-doped MnO2 nanoparticles for enhanced oxidation and detoxication of organic dye waste.

Developing low-cost and efficient materials for dye pollutant removal under mild condition remains a great challenge. Here K+ and Tb3+ co-doped porous MnO2 (K-Tb-MnO2) nanoparticles with tailored properties including crystal structure, surface area and catalytic activity have been synthesized. Experimental results reveal that K-Tb-MnO2 nanoparticle has higher specific surface area, Mn3+ content and surface oxygen vacancies than pristine MnO2 nanoparticle and single-doped MnO2 materials, showing the uniqueness of dual-doped metal ions. Using methyl blue (MB) as a model pollutant, its removal efficiency by K-Tb-MnO2 nanoparticles within 5 min is 93.6%, which is 18, 8.3, and 2.9 times higher than that of MnO2, K-MnO2, and Tb-MnO2 nanomaterials, respectively. Oxalic acid triggered MnO2 material dissolving assay and FT-IR spectrum suggested that remarkable performance of K-Tb-MnO2 nanoparticle toward MB removal can be attributed to a combined effect of adsorption (16% MB removal) and catalytic degradation (84% MB removal). Moreover, K-Tb-MnO2 nanoparticle mediated MB degradation is demonstrated to be a combination of non-radical oxidation by Mn3+ and radical-participated degradation, with 1O2 as the main species. And the intermediates and pathways of MB degradation were studied by liquid chromatography-mass spectrometry. Importantly, cell viability experiment suggests that the toxicity of MB dye could be efficiently alleviated after the treatment with K-Tb-MnO2 nanoparticle. These results demonstrate the great potential of the novel K-Tb-MnO2 particles to be used as a highly effective nanomaterials to reduce the risk of dye wastes toward the environment and human health.