BmC/EBPZ gene is essential for the larval growth and development of silkworm, Bombyx mori.

The genetic male sterile line (GMS) of the silkworm Bombyx mori is a recessive mutant that is naturally mutated from the wild-type 898WB strain. One of the major characteristics of the GMS mutant is its small larvae. Through positional cloning, candidate genes for the GMS mutant were located in a region approximately 800.5 kb long on the 24th linkage group of the silkworm. One of the genes was Bombyx mori CCAAT/enhancer-binding protein zeta (BmC/EBPZ), which is a member of the basic region-leucine zipper transcription factor family. Compared with the wild-type 898WB strain, the GMS mutant features a 9 bp insertion in the 3'end of open reading frame sequence of BmC/EBPZ gene. Moreover, the high expression level of the BmC/EBPZ gene in the testis suggests that the gene is involved in the regulation of reproduction-related genes. Using the CRISPR/Cas9-mediated knockout system, we found that the BmC/EBPZ knockout strains had the same phenotypes as the GMS mutant, that is, the larvae were small. However, the larvae of BmC/EBPZ knockout strains died during the development of the third instar. Therefore, the BmC/EBPZ gene was identified as the major gene responsible for GMS mutation.

Kinome and phosphoproteome reprogramming underlies the aberrant immune responses in critically ill COVID-19 patients.

SARS-CoV-2 infection triggers extensive host immune reactions, leading to severe diseases in certain individuals. However, the molecular basis underlying the excessive yet non-productive immune responses in severe COVID-19 remains incompletely understood. In this study, we conducted a comprehensive analysis of the peripheral blood mononuclear cell (PBMC) proteome and phosphoproteome in sepsis patients positive or negative for SARS-CoV-2 infection, as well as healthy subjects, using quantitative mass spectrometry. Our findings demonstrate dynamic changes in the COVID-19 PBMC proteome and phosphoproteome during disease progression, with distinctive protein or phosphoprotein signatures capable of distinguishing longitudinal disease states. Furthermore, SARS-CoV-2 infection induces a global reprogramming of the kinome and phosphoproteome, resulting in defective adaptive immune response mediated by the B and T lymphocytes, compromised innate immune responses involving the SIGLEC and SLAM family of immunoreceptors, and excessive cytokine-JAK-STAT signaling. In addition to uncovering host proteome and phosphoproteome aberrations caused by SARS-CoV-2, our work recapitulates several reported therapeutic targets for COVID-19 and identified numerous new candidates, including the kinases PKG1, CK2, ROCK1/2, GRK2, SYK, JAK2/3, TYK2, DNA-PK, PKCδ, and the cytokine IL-12.

The effects of co-invasion by three Asteraceae invasive alien species on plant taxonomic and functional diversity in herbaceous ruderal communities in southern Jiangsu, China.

Invasive alien species can affect plant taxonomic and functional diversity. Multiple invasive alien species can co-invade the same plant community. However, the effects of such co-invasion on plant taxonomic and functional diversity are currently unclear. Our study aimed to estimate the effects of co-invasion by three Asteraceae invasive alien species (i.e., Conyza canadensis (L.) Cronquist, Conyza sumatrensis (S.F. Blake) Pruski and G. Sancho, and Solidago canadensis L.) on plant taxonomic and functional diversity in herbaceous ruderal communities in southern Jiangsu, China. The effects of these three invasive alien species under seven invasion combinations (including invasion by one invasive alien species, co-invasion by two invasive alien species, and co-invasion by these three invasive alien species) on plant taxonomic and functional diversity were investigated in a comparative field study of herbaceous ruderal communities. Niche differentiation mediated the functional divergence between these three invasive alien species and natives under all invasion combinations. These three invasive alien species significantly increased plant taxonomic diversity (especially plant diversity and richness) and plant functional diversity (especially Rao's quadratic entropies) under all invasion combinations. The relative abundance of invasive alien species was significantly positively associated with plant functional diversity (especially community-weighted mean trait values and Rao's quadratic entropy). The number of invasive alien species was significantly positively associated with plant taxonomic diversity (especially plant diversity and richness) and plant functional diversity (especially Rao's quadratic entropies). Thus, co-invasion by these three invasive alien species may synergistically increase plant taxonomic diversity (especially plant diversity and richness) and functional diversity (especially Rao's quadratic entropies).

Single-Cell Mapping of Brain Myeloid Cell Subsets Reveals Key Transcriptomic Changes Favoring Neuroplasticity after Ischemic Stroke.

Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.

Genetic and transcriptome analysis of the smb mutant in Bombyx mori.

More than 600 mutations have been discovered in the history of silkworm domestication. It is important to study the formation mechanism of these mutations to further understand the life and development process of silkworms and agricultural pest control. The silkworm mutant smb was isolated from silkworm strain NCV, and transcriptome analysis was performed on the silkworm mutant. 796 differentially expressed genes (DEGs) were detected at 48 h of the second instar stage with 669 genes significantly upregulated and 127 genes significantly downregulated. During the GO enrichment analysis, it was found that the enrichment of biological processes was mainly concentrated in proteolysis, carbohydrate metabolism, aminoglycan metabolism, organic substance metabolism, protein metabolism and so on. Based on the analysis of KEGG pathways, it revealed that the pathways enriched in lysosomes, AMPK signaling, fatty acid metabolism, PPAR signaling, galactose metabolism, and protein digestion and absorption were the most significant. Through these most significantly enriched GO terms and KEGG pathways, DEGs consistent with the phenotypic characteristics of the smb mutant were identified, including small body size, slow development, and successive death after the fourth instar. These results provided experimental evidence for the potential formation mechanism of smb mutants.

Blockade of CCR5 suppresses paclitaxel-induced peripheral neuropathic pain caused by increased deoxycholic acid.

Paclitaxel leads to peripheral neuropathy (paclitaxel-induced peripheral neuropathy [PIPN]) in approximately 50% of cancer patients. At present, there are no effective treatment strategies for PIPN, the mechanisms of which also remain unclear. In this study, we performed microbiome and metabolome analysis of feces and serum from breast cancer patients with different PIPN grades due to paclitaxel treatment. Our analysis reveals that levels of deoxycholic acid (DCA) are highly increased because of ingrowth of Clostridium species, which is associated with severe neuropathy. DCA, in turn, elevates serum level of C-C motif ligand 5 (CCL5) and induces CCL5 receptor 5 (CCR5) overexpression in dorsal root ganglion (DRG) through the bile acid receptor Takeda G-protein-coupled receptor 5 (TGR5), contributing to neuronal hyperexcitability. Consistent with this, administration of CCR5 antagonist maraviroc suppresses the development of neuropathic nociception. These results implicate gut microbiota/bile acids/CCR5 signaling in the induction of PIPN, thus suggesting a target for PIPN treatment.

The co-phytotoxicity of two Asteraceae invasive plants Solidago canadensis L. and Bidens pilosa L. with different invasion degrees.

The phytotoxicity of invasive plants (IPS) has been identified as one of the main factors influencing their invasion success. The invasion of IPS can occur to varying degrees in the habitats. Two IPS can invade one habitat. This study aimed to evaluate the mono- and co-phytotoxicity of two Asteraceae IPS Solidago canadensis L. and Bidens pilosa L. with different invasion degrees (including light invasion (relative abundance <50%) and heavy invasion (relative abundance ≥50%)) on the horticultural Asteraceae species Lactuca sativa L., through a hydroponic experiment conducted on 9 cm Petri dishes. Leaf extracts of the two IPS can cause significant mono- and co-phytotoxicity. The mono- and co-phytotoxicity of the two IPS were concentration-dependent. The mono-phytotoxicity of S. canadensis was significantly increased with increasing invasion degree, but the opposite was true for the mono-phytotoxicity of B. pilosa. Leaf extracts of B. pilosa with light invasion caused stronger phytotoxicity than those of S. canadensis with light invasion. There may be an antagonistic effect for the co-phytotoxicity caused by mixed leaf extracts of the two IPS compared with those of either S. canadensis or B. pilosa. The phytotoxicity of the two IPS on the growth performance of neighboring plants may play a more important role in their mono-invasion than in their co-invasion. The phytotoxicity appeared to affect the growth performance of S. canadensis individuals more significantly when the invasion was heavy, while the growth performance of B. pilosa individuals seemed to be more influenced by phytotoxicity when the invasion was light. Consequently, the concentration of leaf extracts of IPS, the invasion degree of IPS, the species identity of IPS, and the species number of IPS modulated the mono- and co-phytotoxicity of the two IPS.

Effect of physical activity on risk of Alzheimer's disease: A systematic review and meta-analysis of twenty-nine prospective cohort studies.

OBJECTIVE: Physical activity (PA) is beneficial in reductions of all-cause mortality and dementia. However, whether Alzheimer's disease (AD) risk is modified by PA remains disputable. This meta-analysis aims to disclose the underlying relationship between PA and incident AD. METHODS: Pubmed, Embase, Cochrane Library, and Web of Science were retrieved from inception to June 2023. Random-effects models were employed to derive the effect size, represented by hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Twenty-nine prospective cohort studies involving 2068,519 participants were included. The pooled estimate showed a favorable effect of PA on AD risk decline (HR 0.72, 95% CI 0.65-0.80). This association remained robust after adjusting for maximum confounders (HR 0.85, 95% CI 0.79-0.91). Subgroup analysis of PA intensity demonstrated an inverse dose-response relationship between PA and AD, effect sizes of which were significant in moderate (HR 0.85, 95% CI 0.80-0.93) and high PA (HR 0.56, 95% CI 0.45-0.68), but not in low PA (HR 0.94, 95% CI 0.77-1.15). Regardless of all participants or the mid-life cohort, the protection of PA against AD appeared to be valid in shorter follow-up (<15 years) rather than longer follow-up (≥15 years). In addition to follow-up, the robustness of the estimates persisted in supplementary meta-analyses, meta-regression analyses, and sensitivity analyses. CONCLUSION: PA intervention reduces the incidence of AD, but merely in moderate to vigorous PA with follow-up of less than 15 years, thus conditionally recommending the popularization of PA as a modifiable lifestyle factor to prevent AD.

Association between serum triglyceride to high-density lipoprotein cholesterol ratio and sarcopenia among elderly patients with diabetes: a secondary data analysis of the China Health and Retirement Longitudinal Study.

OBJECTIVE: Previous studies investigating the association between the serum triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and the occurrence of sarcopenia in different populations have yielded inconsistent results. This study aimed to investigate the potential association between TG/HDL-C ratio and sarcopenia among elderly Chinese patients with diabetes. DESIGN: A secondary data analysis. SETTING: This was a secondary analysis of data from the China Health and Retirement Longitudinal Study. PARTICIPANTS: In this study, 752 elderly individuals with diabetes were included after excluding individuals aged <60 years old, those with missing data for the assessment of sarcopenia and missing measurements for plasma glucose or glycated haemoglobin. OUTCOME MEASURES: The primary information included TG/HDL-C ratio, muscle strength, physical performance, muscle mass and covariables. The association between TG/HDL-C ratio and sarcopenia was assessed using ordinal logistic regression and linear regression analysis. RESULTS: On multivariate ordinal logistic regression, among male patients, compared with those with the lowest quartile of TG/HDL-C ratio (≤1.41), those with the highest quartile (>4.71) had a significantly lower risk of more severe sarcopenia (OR 0.24, 95% CI 0.10 to 0.54). Similarly, among female patients, compared with those with the lowest quartile of TG/HDL-C ratio (≤2.07), those with the highest quartile (>5.61) had a significantly lower risk of more severe sarcopenia (OR 0.17, 95% CI 0.07 to 0.44). In multivariate linear regression, male patients with the highest quartile of TG/HDL-C ratio (ß=0.36, 95% CI 0.20 to 0.51) had higher muscle mass than those with the lowest quartile. Similarly, female patients with the highest quartile of TG/HDL-C ratio (ß=0.31, 95% CI 0.10 to 0.51) had higher muscle mass than those with the lowest quartile. CONCLUSIONS: There was a negative association between TG/HDL-C ratio categorised by quartile and sarcopenia, which indicates that a higher TG/HDL-C ratio may be related to better muscle status.

A method for quantifying relative competitive advantage and the combined effect of co-invasion for two invasive plants.

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Heavy Metal Contamination Alters the Co-Decomposition of Leaves of the Invasive Tree Rhus typhina L. and the Native Tree Koelreuteria paniculata Laxm.

Invasive and native plants can coexist in the same habitat; however, the decomposition process may be altered by the mixing of invasive and native leaves. Heavy metal contamination may further alter the co-decomposition of both leaf types. This study evaluated the effects of two concentrations (35 mg·L-1 and 70 mg·L-1) and three types (Pb, Cu, and combined Pb + Cu) of heavy metal contamination on the co-decomposition of leaves of the invasive tree Rhus typhina L. and the native tree Koelreuteria paniculata Laxm, as well as the mixed effect intensity of the co-decomposition of the mixed leaves. A polyethylene litterbag experiment was performed over six months. The decomposition coefficient of the two trees, mixed effect intensity of the co-decomposition, soil pH and enzymatic activities, soil bacterial alpha diversity, and soil bacterial community structure were determined. A high concentration of Pb and combined Pb + Cu significantly reduced the decomposition rate of R. typhina leaves. A high concentration of Pb or Cu significantly reduced the decomposition rate of the mixed leaves. In general, R. typhina leaves decomposed faster than K. paniculata leaves did. There were synergistic effects observed for the co-decomposition of the mixed leaves treated with combined Pb + Cu, regardless of concentration, but there were antagonistic effects observed for the co-decomposition of the mixed leaves treated with either Pb or Cu, regardless of concentration. A high concentration of Pb or Cu may increase antagonistic effects regarding the co-decomposition of mixed-leaf groups. Thus, heavy metal contamination can significantly affect the intensity of the mixed effect on the co-decomposition of heterogeneous groups of leaves.

Transcriptome analysis of anorexic and preferred silkworms (Bombyx mori) on artificial diet.

The silkworm, Bombyx mori, is an important oligophagous economic insect and feeding habits of different silkworm varieties to artificial diet are different. Research on the mechanisms of feeding habits on artificial diet, and breeding of silkworm varieties adapted on artificial diet, which is a necessary condition for industrial silkworm rearing, is currently lacking. For an artificial diet, Xin was anorexic, whereas Haoyue A showed a strong appetite. When the two varieties were crossed, the F1 generation showed a poor appetite for the artificial diet and had a setae dispersion rate of <50 %. However, the F2 generation, self-bred progeny of F1, had a good appetite for the artificial diet, with a setae dispersion rate of 70 %. Herein, transcriptome analysis was conducted on the F2 generation, comparing individuals with anorexic and preferred feeding habits, and 2188 differential genes were identified, with 1524 genes up-regulated and 934 genes down-regulated. Several genes were identified to contribute to feeding habits, such as genes involved olfactory system, energy supply, and cell proliferation and differentiation. GO enrichment revealed a large number of DEGs related to behavior, growth, signaling, developmental process, response to stimulation, and other pathways. Furthermore, proteins closely related to feeding were expressed differently. Some DEGs were selected for qRT-PCR, and results indicated the reliability of the DEG results. The DEGs between individuals with anorexic and preferred feeding habits were screened by RNA-Seq technology, which provides a reliable reference to study molecule mechanisms of feeding habits on artificial diet.

What modulates the impacts of acid rain on the allelopathy of the two Asteraceae invasives?

Most of the allelopathic studies have focused on the independent allelopathy of one invasive plant, but have ignored the co-allelopathy of the two invasives. The variations in the type of acid rain can modulate the invasiveness of invasives via the changes in the allelopathy. Thus, it is vital to elucidate the allelopathy of invasives, particularly the co-allelopathy of the two invasives, under acid rain with different types, to illuminate the mechanisms driving the co-invasion of two invasives under diversified acid rain. However, little progress has been finished in this aspect presently. This study aimed to evaluate the co-allelopathy of two Asteraceae invasives Solidago canadensis L. and Erigeron annuus L. treated with acid rain with different nitrogen-to-sulfur ratios on seed germination and seedling growth of the horticultural Asteraceae species Lactuca sativa L. via a hydroponic experiment. Aqueous extracts of the two Asteraceae invasives generated obvious allelopathy on L. sativa. S. canadensis aqueous extracts caused stronger allelopathy. There may be an antagonistic effect for the co-allelopathy of the two Asteraceae invasives. Nitric acid at pH 5.6 weakened the allelopathy of the two Asteraceae invasives, but the other types of acid rain strengthened the allelopathy of the two Asteraceae invasives. The allelopathy of the two Asteraceae invasives increases with the increasing acidity of acid rain, but the allelopathy of the two Asteraceae invasives decreases with the increasing nitrogen-to-sulfur ratio of acid rain. Accordingly, the species number of invasives, and the acidity and type of acid rain modulated the impacts of acid rain on the allelopathy of the two Asteraceae invasives.

Prognostic Signature for Human Umbilical Cord Mesenchymal Stem Cell Treatment of Ischemic Cerebral Infarction by Integrated Bioinformatic Analysis.

In recent studies, stem cell-based therapy is a potential new approach in the treatment of stroke. The mechanism of human umbilical cord mesenchymal stem cell (hUMSC) transplantation as one of the new approaches in the treatment of ischemic stroke is still unclear. The aim of this study was to determine the traits of immune responses during stroke progression after treatment with human umbilical cord blood MSCs by bioinformatics, to predict potential prognostic biomarkers that could lead to sex differences, and to reveal potential therapeutic targets. The microarray dataset GSE78731 (mRNA profile) of middle cerebral artery occlusion (MCAO) rats was obtained from the Gene Expression Omnibus (GEO) database. First, two potentially expressed genes (DEGs) were screened using the Bioconductor R package. Ultimately, 30 specific DEGs were obtained (22 upregulated and 353 downregulated). Next, bioinformatic analysis was performed on these specific DEGs. We performed a comparison for the differentially expressed genes screened from between the hUMSC and MCAO groups. Gene Ontology enrichment and pathway enrichment analyses were then performed for annotation and visualization. Gene Ontology (GO) functional annotation analysis shows that DEGs are mainly enriched in leukocyte migration, neutrophil activation, neutrophil degranulation, the external side of plasma membrane, cytokine receptor binding, and carbohydrate binding. KEGG pathway enrichment analysis showed that the first 5 enrichment pathways were cytokine-cytokine receptor interaction, chemokine signal pathway, viral protein interaction with cytokine and cytokine receptor, cell adhesion molecules (CAMs), and phagosome. The top 10 key genes of the constructed PPI network were screened, including Cybb, Ccl2, Cd68, Ptprc, C5ar1, Il-1b, Tlr2, Itgb2, Itgax, and Cd44. In summary, hUMSC is likely to be a promising means of treating IS by immunomodulation.

Acid deposition at higher acidity weakens the antagonistic responses during the co-decomposition of two Asteraceae invasive plants.

Co-invasion by two invasive plant species (IPS) can occur in the same habitat. Diversified acid deposition may change the co-invasion process by altering litter decomposition and plant-soil feedback signalling. This study examined the co-decomposition of two Asteraceae IPS (Solidago canadensis L. and Bidens pilosa L.) on litter decomposition rate, soil enzyme activities, and soil N-fixing bacterial communities under diversified acid deposition (mixed acid deposition at pH 5.6 and at pH 4.5, sulfuric acid at pH 4.5, and nitric acid at pH 4.5). B. pilosa litter degraded faster than S. canadensis litter. Acid deposition at higher acidity accelerated the decomposition rate of both pure S. canadensis litter and the equally mixed litters from the two Asteraceae IPS. Antagonistic responses may occur during the co-decomposition of the two Asteraceae IPS with mixed acid deposition, regardless of the pH, as well as with nitric acid deposition at pH 4.5; in contrast, there may be neutral responses for the co-decomposition process with sulfuric acid at pH 4.5. The type of acid deposited may be one of the key factors affecting the intensity of the mixing effect affecting the co-decomposition. Acid deposition at higher acidity weakened the antagonistic responses for the co-decomposition of the two Asteraceae IPS compared with the response to weak acids. Together, these results indicate that acid deposition at higher acidity could facilitate the co-invasion of the two Asteraceae IPS mainly through accelerated litter decomposition as well as weakened antagonistic responses for co-decomposition.

Down-Regulation of Insulin Like Growth Factor 1 Involved in Alzheimer's Disease via MAPK, Ras, and FoxO Signaling Pathways.

The inability to halt or even delay the course of Alzheimer's disease (AD) forces the development of new molecular signatures and therapeutic strategies. Insulin like growth factor 1 (IGF1) is a promising target for AD treatment, yet exact mechanisms of AD ascribed to IGF1 remain elusive. Herein, gene expression profiles of 195 samples were analyzed and 19,245 background genes were generated, among which 4,424 differentially expressed genes (DEGs) were overlapped between AD/control and IGF1-low/high groups. Based on such DEGs, seven co-expression modules were established by weight gene correlation network analysis (WGCNA). The turquoise module had the strongest correlation with AD and IGF1-low expression, the DEGs of which were enriched in GABAergic synapse, long-term potentiation, mitogen-activated protein kinase (MAPK), Ras, and forkhead box O (FoxO) signaling pathways. Furthermore, cross-talking pathways of IGF1, including MAPK, Ras, and FoxO signaling pathways were identified in the protein-protein interaction network. According to the area under the curve (AUC) analysis, down-regulation of IGF1 exhibited good diagnostic performance in AD prediction. Collectively, our findings highlight the involvement of low IGF1 in AD pathogenesis via MAPK, Ras, and FoxO signaling pathways, which might advance strategies for the prevention and therapy of AD based on IGF1 target.

Circ_0000291 contributes to hepatocellular carcinoma tumorigenesis by binding to miR-1322 to up-regulate UBE2T.

INTRODUCTION AND OBJECTIVES: Circular RNAs (circRNAs) are identified to show important regulatory functions in cancer biology. We attempted to analyze the role of circ_0000291 in hepatocellular carcinoma (HCC) progression and its related mechanism. METHODS: The circular characteristic of circ_0000291 was tested using exonuclease RNase R. Cell proliferation was analyzed by 5-Ethynyl-2'-deoxyuridine (EdU) incorporation and colony formation assays. Cell apoptosis was measured by flow cytometry and a caspase 3 activity assay kit. Transwell assays were performed to analyze cell migration and invasion abilities. Sphere formation assay was conducted to analyze cell stemness. Dual-luciferase reporter and RNA-pull down assays were conducted to verify the interaction between microRNA-1322 (miR-1322) and circ_0000291 or ubiquitin conjugating enzyme E2 T (UBE2T). RESULTS: Circ_0000291 was markedly up-regulated in HCC tissues and cell lines. HCC patients with high expression of circ_0000291 displayed a low survival rate. Circ_0000291 knockdown restrained the proliferation, migration, invasion, and stemness and induced the apoptosis of HCC cells. Circ_0000291 directly interacted with miR-1322 and negatively regulated miR-1322 expression. Circ_0000291 knockdown-mediated anti-tumor impacts in HCC cells were largely overturned by the interference of miR-1322. miR-1322 directly paired with the 3' untranslated region (3'UTR) of UBE2T, and UBE2T was negatively regulated by miR-1322. UBE2T overexpression largely reversed circ_0000291 silencing-induced effects in HCC cells. Circ_0000291 positively regulated UBE2T expression by absorbing miR-1322 in HCC cells. Circ_0000291 silencing notably reduced the tumorigenic potential in vivo. CONCLUSION: Circ_0000291 facilitated HCC progression by targeting miR-1322/UBE2T axis, which provided novel potential biomarkers and targets for HCC patients.

Long-term modification of gut microbiota by broad-spectrum antibiotics improves stroke outcome in rats.

BACKGROUND: The brain-gut axis is a major regulator of the central nervous system. We investigated the effects of treatment with broad-spectrum antibiotics on gut and brain inflammation, infarct size and long-term behavioral outcome after cerebral ischemia in rats. METHODS: Rats were treated with broad-spectrum antibiotics (ampicillin, vancomycin, ciprofloxacin, meropenem and metronidazole) for 4 weeks before the endothelin-1 induced ischemia. Treatment continued for 2 weeks until the end of behavioral testing, which included tapered ledged beam-walking, adhesive label test and cylinder test. Gut microbiome, short-chain fatty acids and cytokine levels were measured together with an assessment of infarct size, neuroinflammation and neurogenesis. RESULTS: The results revealed that the antibiotics exerted a clear impact on the gut microbiota. This was associated with a decrease in systemic and brain cytokine levels, infarct size and apoptosis in the perilesional cortex and improved behavioral outcome. CONCLUSION: Our results highlighted the significant relationship between intestinal microbiota and beneficial neuro-recovery after ischemic stroke.

Molecular Signatures of Mitochondrial Complexes Involved in Alzheimer's Disease via Oxidative Phosphorylation and Retrograde Endocannabinoid Signaling Pathways.

Objective: The inability to intervene in Alzheimer's disease (AD) forces the search for promising gene-targeted therapies. This study was aimed at exploring molecular signatures and mechanistic pathways to improve the diagnosis and treatment of AD. Methods: Microarray datasets were collected to filter differentially expressed genes (DEGs) between AD and nondementia controls. Weight gene correlation network analysis (WGCNA) was employed to analyze the correlation of coexpression modules with AD phenotype. A global regulatory network was established and then visualized using Cytoscape software to determine hub genes and their mechanistic pathways. Receiver operating characteristic (ROC) analysis was conducted to estimate the diagnostic performance of hub genes in AD prediction. Results: A total of 2,163 DEGs from 13,049 background genes were screened in AD relative to nondementia controls. Among the six coexpression modules constructed by WGCNA, DEGs of the key modules with the strongest correlation with AD were extracted to build a global regulatory network. According to the Maximal Clique Centrality (MCC) method, five hub genes associated with mitochondrial complexes were chosen. Further pathway enrichment analysis of hub genes, such as oxidative phosphorylation and retrograde endocannabinoid signaling, was identified. According to the area under the curve (AUC) of about 70%, each hub gene exhibited a good diagnostic performance in predicting AD. Conclusions: Our findings highlight the perturbation of mitochondrial complexes underlying AD onset, which is mediated by molecular signatures involved in oxidative phosphorylation (COX5A, NDUFAB1, SDHB, UQCRC2, and UQCRFS1) and retrograde endocannabinoid signaling (NDUFAB1) pathways.