Host genetics and larval host plant modulate microbiome structure and evolution underlying the intimate insect-microbe-plant interactions in Parnassius species on the Qinghai-Tibet Plateau.

Insects harbor a remarkable diversity of gut microbiomes critical for host survival, health, and fitness, but the mechanism of this structured symbiotic community remains poorly known, especially for the insect group consisting of many closely related species that inhabit the Qinghai-Tibet Plateau. Here, we firstly analyzed population-level 16S rRNA microbial dataset, comprising 11 Parnassius species covering 5 subgenera, from 14 populations mostly sampled in mountainous regions across northwestern-to-southeastern China, and meanwhile clarified the relative importance of multiple factors on gut microbial community structure and evolution. Our findings indicated that both host genetics and larval host plant modulated gut microbial diversity and community structure. Moreover, the effect analysis of host genetics and larval diet on gut microbiomes showed that host genetics played a critical role in governing the gut microbial beta diversity and the symbiotic community structure, while larval host plant remarkably influenced the functional evolution of gut microbiomes. These findings of the intimate insect-microbe-plant interactions jointly provide some new insights into the correlation among the host genetic background, larval host plant, the structure and evolution of gut microbiome, as well as the mechanisms of high-altitude adaptation in closely related species of this alpine butterfly group.

LINC01977 promotes colorectal cancer growth and metastasis by enhancing aerobic glycolysis via the ERK/c-Myc axis.

Background: How colorectal cancer (CRC) gain the ability to growth and metastasis remains largely unknown. Findings from preceding studies have revealed the participation of long non-coding RNAs (lncRNAs) in CRC progression. However, the role of LINC01977 in CRC remains unexplored. This study aims to explore the function and underlying mechanism of LINC01977 in CRC. Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to analyze the expression of LINC01977 in CRC and its correlation with CRC prognosis. In our research, we explored the influence of LINC01977 on CRC progression such as cell proliferation, migration, invasion, and aerobic glycolysis, and identified its fundamental molecular mechanism using in vitro CRC cell lines and in vivo mouse xenograft models. Results: LINC01977 exhibited significantly elevated expression in CRC tissues and cell lines, and its level was significantly correlated with malignant clinicopathological characteristics and negative prognosis. Furthermore, both in vivo and in vitro tests revealed LINC01977's role in facilitating CRC cell proliferation and metastasis. LINC01977's significant part in CRC aerobic glycolysis was also discovered. With an aim to uncover the underlying mechanism, we investigated LINC01977's effect on c-Myc, a key gene in glycolysis. The results showed that LINC01977 regulated c-Myc stability via extracellular signal-regulated kinase (ERK)-mediated phosphorylation, and LINC01977-mediated c-Myc activated the level of vital glycolysis-related genes such as HK2, PGK1, LDHA, and GLUT1. Rescue experiments further confirmed that LINC01977 promoted CRC proliferation, metastasis, and aerobic glycolysis via c-Myc. Conclusions: This study is the first to report that LINC01977 facilitates CRC proliferation, metastasis, and aerobic glycolysis through c-Myc, suggesting its potential as a therapeutic target for CRC treatment.

Effect of Butylphthalide soft capsules on cognitive function and dementia-related factors in elderly patients with Parkinson's disease dementia during the COVID-19 pandemic.

OBJECTIVE: To observe the effect of Butylphthalide soft capsules on improving cognitive function, activity of daily living, and dementia-related factors of elderly patients with Parkinson's disease dementia (PDD) during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: The clinical data of 126 elderly patients with PDD admitted to the Second Affiliated Hospital of Zhengzhou University during the COVID-19 pandemic were analyzed retrospectively. Patients were assigned to a control group (conventional clinical treatment, n=50) and a research group (conventional clinical treatment combined with Butylphthalide soft capsules, n=76). The clinical response, clinical symptoms, cognitive function, activity of daily living (ADL), cerebral blood flow velocity, serum inflammatory factors, oxidative stress indices, neurotrophic factors, dementia-related factors, and drug safety were analyzed and compared between the two groups. RESULTS: The overall response rate was significantly higher in the research group than in the control group (97.37% vs. 84.00%, P=0.017). After treatment, the clinical symptom-based scores and levels of serum inflammatory factors, malondialdehyde, and Parkinson disease protein 7 were significantly lower in the research group than in the control group (all P<0.001); the cognitive function and ADL scores, cerebral blood flow velocities, and levels of catalase, glutathione peroxidase, superoxide dismutase, neurotrophic factors, and neurotrophin-3 were significantly higher in the research group (all P<0.001). The incidence of adverse reactions was comparable between the two groups (4.00% vs. 6.58%, P=0.825). CONCLUSION: Butylphthalide soft capsules have a definite effect and good safety in elderly patients with PDD during the COVID-19 pandemic.

The spatial landscape of T cells in the microenvironment of stage III lung adenocarcinoma.

This study aimed to provide more information for prognostic stratification for patients through an analysis of the T-cell spatial landscape. It involved analyzing stained tissue sections of 80 patients with stage III lung adenocarcinoma (LUAD) using multiplex immunofluorescence and exploring the spatial landscape of T cells and their relationship with prognosis in the center of the tumor (CT) and invasive margin (IM). In this study, multivariate regression suggested that the relative clustering of CT CD4+ conventional T cell (Tconv) to inducible Treg (iTreg), natural regulatory T cell (nTreg) to Tconv, terminal CD8+ T cell (tCD8) to helper T cell (Th), and IM Treg to tCD8 and the relative dispersion of CT nTreg to iTreg, IM nTreg to nTreg were independent risk factors for DFS. Finally, we constructed a spatial immunological score named the GT score, which had stronger prognostic correlation than IMMUNOSCORE® based on CD3/CD8 cell densities. The spatial layout of T cells in the tumor microenvironment and the proposed GT score can reflect the prognosis of patients with stage III LUAD more effectively than T-cell density. The exploration of the T-cell spatial landscape may suggest potential cell-cell interactions and therapeutic targets and better guide clinical decision-making. © 2024 The Pathological Society of Great Britain and Ireland.

Dispersal from the Qinghai-Tibet plateau by a high-altitude butterfly is associated with rapid expansion and reorganization of its genome.

Parnassius glacialis is a typical "Out of the QTP" alpine butterfly that originated on the Qinghai-Tibet Plateau (QTP) and dispersed into relatively low-altitude mountainous. Here we assemble a chromosome-level genome of P. glacialis and resequence 9 populations in order to explore the genome evolution and local adaptation of this species. These results indicated that the rapid accumulation and slow unequal recombination of transposable elements (TEs) contributed to the formation of its large genome. Several ribosomal gene families showed extensive expansion and selective evolution through transposon-mediated processed pseudogenes. Additionally, massive structural variations (SVs) of TEs affected the genetic differentiation of low-altitude populations. These low-altitude populations might have experienced a genetic bottleneck in the past and harbor genes with selective signatures which may be responsible for the potential adaptation to low-altitude environments. These results provide a foundation for understanding genome evolution and local adaptation for "Out of the QTP" of P. glacialis.

Multi-Class Weed Recognition Using Hybrid CNN-SVM Classifier.

The Convolutional Neural Network (CNN) is one of the widely used deep learning models that offers the chance to boost farming productivity through autonomous inference of field conditions. In this paper, CNN is connected to a Support Vector Machine (SVM) to form a new model CNN-SVM; the CNN models chosen are ResNet-50 and VGG16 and the CNN-SVM models formed are ResNet-50-SVM and VGG16-SVM. The method consists of two parts: ResNet-50 and VGG16 for feature extraction and SVM for classification. This paper uses the public multi-class weeds dataset DeepWeeds for training and testing. The proposed ResNet-50-SVM and VGG16-SVM approaches achieved 97.6% and 95.9% recognition accuracies on the DeepWeeds dataset, respectively. The state-of-the-art networks (VGG16, ResNet-50, GoogLeNet, Densenet-121, and PSO-CNN) with the same dataset are accurate at 93.2%, 96.1%, 93.6%, 94.3%, and 96.9%, respectively. In comparison, the accuracy of the proposed methods has been improved by 1.5% and 2.7%, respectively. The proposed ResNet-50-SVM and the VGG16-SVM weed classification approaches are effective and can achieve high recognition accuracy.

Loss of NDUFS1 promotes gastric cancer progression by activating the mitochondrial ROS-HIF1α-FBLN5 signaling pathway.

BACKGROUND: Recent studies suggested that NDUFS1 has an important role in human cancers; however, the effects of NDUFS1 on gastric cancer (GC) are still not fully understood. METHODS: We confirmed that NDUFS1 is downregulated in GC cells through western blot immunohistochemistry and bioinformation analysis. The effect of NDUFS1 on GC was studied by CCK-8, colony formation, transwell assay in vitro and Mouse xenograft assay in vivo. Expression and subcellular localization of NDUFS1 and the content of mitochondrial reactive oxygen species (mROS) was observed by confocal reflectance microscopy. RESULTS: Reduced expression of NDUFS1 was found in GC tissues and cell lines. Also, NDUFS1 overexpression inhibited GC cell proliferation, migration, and invasion in vitro as well as growth and metastasis in vivo. Mechanistically, NDUFS1 reduction led to the activation of the mROS-hypoxia-inducible factor 1α (HIF1α) signaling pathway. We further clarified that NDUFS1 reduction upregulated the expression of fibulin 5 (FBLN5), a transcriptional target of HIF1α, through activation of mROS-HIF1α signaling in GC cells. CONCLUSIONS: The results of this study indicate that NDUFS1 downregulation promotes GC progression by activating an mROS-HIF1α-FBLN5 signaling pathway.

Increasing the peroxidase-like activity of the MIL-100(Fe) nanozyme by encapsulating Keggin-type 12-phosphomolybdate and covering three-dimensional graphene.

To improve the peroxidase-like activities of metal-organic frameworks (MOFs) as nanozymes, a ternary MIL-100(Fe)@PMo12@3DGO nanocomposite was designed and fabricated by encapsulating Keggin-type H3PMo12O40 (PMo12) with fast and reversible multi-electron redox processes and an electron-rich structure into MIL-100(Fe), then being covered by three-dimensional graphene (3DGO) with higher conductivity, larger surface area, higher porosity, and better chemical stability. As a consequence, the as-prepared MIL-100(Fe)@PMo12@3DGO nanocomposite exhibits excellent peroxidase-like activities, namely, the lowest limit of detection (0.14 µM) in the range of 1-100 µM for glucose to date, to the best of our knowledge, attributed to the individual and synergistic effects of H3PMo12O40, 3DGO and MIL-100(Fe).

Giant isolated half-cycle attosecond pulses generated in coherent bremsstrahlung emission regime.

Giant half-cycle attosecond pulse generation in the coherent bremsstrahlung emission regime is proposed for laser pulses with normal incidence on a double-foil target, where the first foil is transparent and the second foil is opaque. The presence of the second opaque target contributes to the formation of a relativistic flying electron sheet (RFES) from the first foil target. After the RFES has passed through the second opaque target, it is decelerated sharply, and bremsstrahlung emission occurs, which results in the generation of an isolated half-cycle attosecond pulse having an intensity of ∼1.4×10^{22}W/cm^{2} and a duration of 3.6 as. The generation mechanism does not require extra filters and may open a regime of nonlinear attosecond science.

Asynchronous control for semi-Markov switching systems with singular perturbation and an improved protocol.

This study addresses the asynchronous control problem for a semi-Markov switching system in the presence of singular perturbation and an improved triggering protocol. To decrease the occupation of network resources, an improved protocol is skillfully established by adopting two auxiliary offset variables. Unlike the existing protocols, the established improved protocol is capable of arranging information transmission with more degrees of freedom, thereby reducing the communication frequency and maintaining control performance. Apart from the reported hidden Markov model, a nonhomogeneous hidden semi-Markov model is used to handle the mode mismatch between the systems and controllers. Benefiting from Lyapunov techniques, parameter-dependent sufficient conditions are devised to ensure a stochastically stable subject to a predetermined performance. Finally, the validity and practicability of the theoretical results are verified via a numerical example and a tunnel diode circuit model.

ZIF-67 on Sulfur-Functionalized Graphene Oxide for Lithium-Sulfur Batteries.

How to overcome the problem of fast capacity fading and low sulfur utilization is the key to promote the practical applications of lithium-sulfur (Li-S) batteries. Based on the fact that sulfur-functionalized graphene oxide (GO-S) can avoid the loss of sulfur/polysulfides through the strong C-S interaction, and the zeolitic imidazolate framework (ZIF-67) can capture sulfur and catalyze lithium polysulfide (Li2Sx, 4 ≤ x ≤ 8), the combination of ZIF-S (ZIF-67 after combining with sulfur) with GO-S can be expected to be an excellent electrode material for Li-S batteries due to the synergistic effect. Herein, ZIF-S@GO-S (n) nanocomposites (n = 1, 2, and 3 for the mass ratio of ZIF-67/GO of 4:1, 6:1, and 8:1, respectively) as the cathode materials in Li-S batteries were successfully fabricated, and ZIF-S@GO-S (2) showed better electrochemical performances and cycle stability with a high specific capacity of 1529.5 mA h g-1 at the initial cycle and 792 mA h g-1 after 500 cycles at 0.1 C (1 C = 1675 mA h g-1). The fact that ZIF-S@GO-S (n) can simultaneously improve the conductivity and utilization of S (C-S···S8 and C-S···SxLi2) and the conversion kinetics of Li2Sx (4 ≤ x ≤ 8) provides a new avenue for designing and fabricating promising cathodes for high-performance Li-S batteries.

Hsa_circ_0046430 promotes the progression of colorectal cancer by targeting miR-6785-5p/SRCIN1 axis as a ceRNA.

The correlation among circular RNAs (circRNAs), microRNAs, and messenger RNAs have gained increasing attention in recent years. However, the mechanism of such discoveries in colorectal cancer (CRC) is not yet elucidated. The present study aimed to clarify whether the novel circRNAs regulate the prognosis-related genes through the competing endogenous RNAs (ceRNA). An analysis of the Weighted Gene Co-Expression Network Analysis was conducted to screen a module-trait circRNAs, and other big data mining technologies were used to predict the related microRNAs and the downstream genes. Prognosis-related gene model was built using the Cox regression analysis for the 138 messenger RNAs associated with hsa circ 0046430. The qRT-PCR was adopted to verify ceRNA network. Immunohistochemistry verified the correlation between SRCIN1 and patient prognosis. In summary, these results demonstrated that hsa_circ_0046430 is a tumor-related circRNA based on the clinical characteristics module of Weighted Gene Co-Expression Network Analysis. The prognostic risk score signature model analysis indicated that CRC risk was independently related to the risk score and SRCIN1 was independently associated with overall survival. Therefore, the hsa_circ_0046430/miR-6785-5p/SRCIN1 axis was constructed. Hsa_circ_0046430/miR-6785-5p/SRCIN1 axis relative expression level was determined by qRT-PCR. Immunohistochemical staining further validated that SCRIN1 was significantly higher in cancer than in adjacent normal tissues. Our study identified and primarily validated the hsa_circ_0046430/miR-6785-5p/SRCIN1 regulatory axis impacted on CRC prognosis, suggesting novel biomarkers and therapeutic targets for CRC patients. Further in-depth studies are essential to confirm the underlying ceRNA mechanism.

Ultrahigh-amplitude isolated attosecond pulses generated by a two-color laser pulse interacting with a microstructured target.

A unique electron nanobunching mechanism using a two-color laser pulse interacting with a microstructured foil is proposed for directly generating ultraintense isolated attosecond pulses in the transmission direction without requiring extra filters and gating techniques. The unique nanobunching mechanism ensures that only one electron sheet contributes to the transmitted radiation. Accordingly, the generated attosecond pulses are unipolar and have durations at the full width at half-maximum about 5 attoseconds. The emitted ultrahigh-amplitude isolated attosecond pulses have intensities of up to ∼10^{21}W/cm^{2}, which are beyond the limitations of weak attosecond pulses generated by gas harmonics sources and may open a new regime of nonlinear attosecond studies. Unipolar pulses can be useful for probing ultrafast electron dynamics in matter via asymmetric manipulation.

Curcumin prevents Alzheimer's disease progression by upregulating JMJD3.

The main purpose of this research was to explore the molecular mechanisms of Jumonji Domain-Containing Protein 3 (JMJD3) in Alzheimer's disease (AD) and to analyze its role in the anti-AD mechanism of curcumin (CUR). In the in vitro study of AD, JMJD3 overexpression promoted the trimethylation of histone H3 lysine 27 (H3K27me3), downregulated brain-derived neurotrophic factor (BDNF ), improved the abnormality of mitochondrial stress response (MSR) markers, Aß accumulation, increased cell proliferation and inhibited apoptosis. Upregulating BDNF also achieved above similar results. Knockout of JMJD3 could downregulate BDNF, upregulate the level of H3K27me3 methylation and inhibit MSR markers, while transfection of JMJD3 RNAi could counteract the upregulated effect of BDNF. Then, MSR activator could also improve AD. In addition, JMJD3 in AD in vitro models was obviously upregulated under CUR stimulation, and it triggered a series of reactions as mentioned above. In the in vivo study, the levels of JMJD3, the mRNA and protein levels of BDNF in the right brain tissues of AD mice were downregulated, the methylation of H3K27me3 increased, and the MSR markers (ClpP, HSP6, HSP-60, ATFS-1, etc.) were downregulated; the above indexes were improved in varying degrees with the intervention of CUR. Thus, we conclude that CUR can induce the upregulation of JMJD3 and improve BDNF expression by promoting the demethylation of H3K27me3, thereby maintaining the balance of MSR and thus, preventing AD development.

Effect of Fu Yan Qing prescription on pelvic effusion, mass absorption and microenvironment of pelvic blood stasis in patients with sequelae of pelvic inflammatory disease of accumulation of dampness heat and blood stasis type.

Objective: To investigate the effect of Fu Yan Qing prescription on sequelae of pelvic inflammatory disease of accumulation of dampness heat and blood stasis type. Methods: Total 80 patients with sequelae of sequelae of pelvic inflammatory disease of accumulation of dampness heat and blood stasis type were admitted to Baoding No.1 Central Hospital from December, 2018 to April, 2020 and divided into two groups according to the random number table, with 40 cases in each group. Patients in the control group were treated with conventional western medicine, while patients in the observation group were treated with Fu Yan Qing prescription orally. The clinical efficacy, the changes of traditional Chinese medicine (TCM) syndromes, local sign scores, visual analog scale (VAS) of pain, pelvic mass size, pelvic fluid volume and uterine blood flow parameters of the two groups before and after treatment were observed and compared, and the safety of the two groups was evaluated. Results: The total efficacy after treatment in the observation group was 87.5%, which was significantly higher than that of 67.5% in the control group (p<0.05). The TCM syndrome scores, local signs scores, pain scores, size of pelvic mass and pelvic effusion in both groups decreased significantly after treatment (p<0.05), PSV indexes of the two groups were significantly increased after treatment (p<0.05), and these changes were even more pronounced in the observation group (p<0.05). Compared with before treatment, PI and RI indexes of the observation group were significantly decreased after treatment (p<0.05). The observation group experienced an adverse reaction in 7.5% cases considerably lower than the 27.5% of the control group (p<0.05). Conclusion: Fu Yan Qing prescription is a safe and reliable treatment for patients with sequelae of pelvic inflammatory disease of accumulation of dampness heat and blood stasis type. It is worth promotion in clinical practice.

Chenodeoxycholic Acid Enhances the Effect of Sorafenib in Inhibiting HepG2 Cell Growth Through EGFR/Stat3 Pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly invasive disease with a high mortality rate. Our previous study found that Chenodeoxycholic acid (CDCA) as an endogenous metabolite can enhance the anti-tumor effect. Sorafenib has limited overall efficacy as a first-line agent in HCC, and combined with CDCA may improve its efficacy. METHODS: HepG2 cells and Balb/c nude mice were used respectively for in vitro and in vivo experiments. Flow cytometry, Western blotting, HE and immunohistochemical staining and immunofluorescence were used to study the effects of CDCA combined with sorafenib on HepG2 cell growth and apoptosis-related proteins. Magnetic bead coupling, protein profiling and magnetic bead immunoprecipitation were used to find the targets of CDCA action. The effect of CDCA on EGFR/Stat3 signaling pathway was further verified by knocking down Stat3 and EGFR. Finally, fluorescence confocal, and molecular docking were used to study the binding site of CDCA to EGFR. RESULTS: In this study, we found that CDCA enhanced the effect of sorafenib in inhibiting the proliferation, migration and invasion of HepG2 cells. Magnetic bead immunoprecipitation and protein profiling revealed that CDCA may enhance the effect of sorafenib by affecting the EGFR/Stat3 signaling pathway. Further results from in vitro and in vivo gene knockdown experiments, confocal experiments and molecular docking showed that CDCA enhances the efficacy of sorafenib by binding to the extracellular structural domain of EGFR. CONCLUSION: This study reveals the mechanism that CDCA enhances the inhibitory effect of sorafenib on HepG2 cell growth in vitro and in vivo, providing a potential new combination strategy for the treatment of HCC.

The predictive value of RNA binding proteins in colon adenocarcinoma.

BACKGROUND: RNA binding proteins (RBPs) play an important role in regulating post-transcriptional gene expression and have been reported to be closely associated with the occurrence and development of tumors. However, the effect of RBPs in colon cancer remains unclear. METHODS: We downloaded clinical information and transcriptome data of colon adenocarcinoma (COAD) from The Cancer Genome Atlas database (TCGA) database. After combining this data, we identified differentially expressed RBPs in normal and cancer tissues and subsequently performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Prognosis-related RBPs were identified via Cox regression analysis. The samples were randomly divided into two groups; an experimental group and a control group. A predictive model was constructed by dividing the experimental group into high- and low-risk subgroups based on the scores of the prognostic-related RBPs, and the prognosis of samples in these two subgroups was compared. Then, this model was applied to the control group. Finally, the model results were verified based on an online survival database and the Human Protein Atlas (HPA) database. RESULTS: A total of 469 differentially expressed RBPs were identified in normal and cancer tissues. Ten prognosis-related RBPs were determined by Cox regression analysis. In the prognostic prediction model, the prognosis of high-risk patients in the experimental group was worse than that in the low-risk group, and the same result was obtained in the control group. In addition, the risk score in the Cox regression analysis showed that the model could be used as an independent prognostic factor (P<0.001). The results of the online survival analysis tool, HPA database, and the model were consistent. CONCLUSIONS: Some specific RBPs are significantly associated with the prognosis of patients with COAD, and this finding may provide important information for the future diagnosis and treatment of patients with COAD.

Intestinal microbiota participates in nonalcoholic fatty liver disease progression by affecting intestinal homeostasis.

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with a pathogenesis that has not been fully elucidated. With the development of the theory of the gut-liver axis and the deepening of related research, the role of the intestinal tract in the pathogenesis of NAFLD has been investigated more. Intestinal microbiota, intestinal metabolites, and intestinal epithelial and immune-based barriers constitute the intestinal environment, which uses crosstalk to maintain the homeostasis of the intestinal environment. This paper reviews the progress in the study of intestinal microbiota, intestinal environment, and NAFLD and suggests that repair of intestinal functional balance may be a new idea for early prevention and intervention of NAFLD.

Extracellular vesicles in neurodegenerative diseases: Insights and new perspectives.

Extracellular vesicles (EVs) are vesicle-like substances released by eukaryotic cells. Based on their origin and size, EVs are mainly divided into exosomes, microvesicles and apoptotic bodies, and they are secreted by eukaryotic cells under physiological and pathological conditions. EVs are enriched with nucleic acids, proteins and other factors. EVs can regulate the function of adjacent and distant cells, and they are even involved in the pathogenesis of diseases. They contain proteins associated with the pathogenesis of neurodegenerative diseases (NDs), such as the α-synuclein (α-syn) and tau proteins, which suggest potential roles for EVs as biomarkers and carriers of drugs and other therapeutic molecules that can cross the blood-brain barrier to treat NDs. In this review, we summarized the function of EVs in the pathogenesis of different NDs and related advances in EVs as diagnostic biomarkers and treatments for diseases.