[Corrigendum] Exosomal microRNA­4516, microRNA­203 and SFRP1 are potential biomarkers of acute myocardial infarction.

Subsequently to the publication of the above article, the authors have realized that, in Fig. 1A, the incorrect image was uploaded to show the ultrastructure of exos isolated from plasma and examined using transmission electron microscopy (essentially, the image in question had already appeared in an article published by the same research group in Journal of Cellular and Molecular Medicine). In addition,  the '+' and '-' signs for the 'Cell lysis' experiments shown underneath the gels in Fig. 1B were incorporated the wrong way around. The revised version of Fig. 1, showing the correct image in Fig. 1A and the correct labels in Fig. 1B, is shown below. Note that the errors made in assembling this figure did not have a major impact on either the results or the conclusions reported in this paper. The authors are grateful to the Editor of Molecular Medicine Reports for allowing them this opportunity to publish a corrigendum, and apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 27: 124, 2023; DOI: 10.3892/mmr.2023.13010].

In situ Raman reveals the critical role of Pd in electrocatalytic CO2 reduction to CH4 on Cu-based catalysts.

Electrocatalytic CO2 reduction reaction (CO2RR) for CH4 production presents a promising strategy to address carbon neutrality, and the incorporation of a second metal has been proven effective in enhancing catalyst performance. Nevertheless, there remains limited comprehension regarding the fundamental factors responsible for the improved performance. Herein, the critical role of Pd in electrocatalytic CO2 reduction to CH4 on Cu-based catalysts has been revealed at a molecular level using in situ surface-enhanced Raman spectroscopy (SERS). A "borrowing" SERS strategy has been developed by depositing Cu-Pd overlayers on plasmonic Au nanoparticles to achieve the in situ monitoring of the dynamic change of the intermediate during CO2RR. Electrochemical tests demonstrate that Pd incorporation significantly enhances selectivity toward CH4 production, and the Faradaic efficiency (FE) of CH4 is more than two times higher than that for the catalysts without Pd. The key intermediates, including *CO2-, *CO, and *OH, have been directly identified under CO2RR conditions, and their evolution with the electrochemical environments has been determined. It is found that Pd incorporation promotes the activation of both CO2 and H2O molecules and accelerates the formation of abundant active *CO and hydrogen species, thus enhancing the CH4 selectivity. This work offers fundamental insights into the understanding of the molecular mechanism of CO2RR and opens up possibilities for designing more efficient electrocatalysts.

Dietary supplementation with Clostridium autoethanogenum protein improves growth performance and promotes muscle protein synthesis by activating the mTOR signaling pathway of the broiler.

The experiment aimed to evaluate the effects of different ratios of Clostridium autoethanogenum protein (CAP) used in the diets on the growth performance, muscle quality, serum indexes, and mTOR pathway of white feather broilers. Four hundred and eighty 1-day-old Arbor Acres (AA) broilers, comprising equal numbers of males and females, were randomly assigned to one of four treatments, and each treatment consisted of 12 replicates of 10 birds. Four diets were formulated based on isoenergetic and isonitrogenous principles. The control group (CAP 0) did not receive any CAP, while the experimental groups received 2% (CAP 2), 3% (CAP 3), and 4% (CAP 4) of CAP for six weeks. Compared with the CAP0, (1) The feed conversion ratio (FCR) was lower (p < 0.05), and the leg muscle yield was higher (p < 0.05) in the CAP3 and CAP4; (2) The serum levels of TP, ALB, T-AOC, and SOD were improved in the CAP3 (p < 0.05); (3) The expression of Lipin-1 gene was down-regulated and AMPKɑ2, Akt, and 4E-BP1 genes were up-regulated in the experiment group (p < 0.05); (4) The inclusion of 3% CAP in the diet increased the levels of 4E-BP1, S6K1, Akt, and AMPKɑ2 phosphorylation by modulating the mTOR signaling pathway (p < 0.05). In conclusion, broiler diets containing 3% CAP can activate the mTOR signaling pathway to promote muscle synthesis and improve growth performance.

Low expression of selenoprotein S induces oxidative damage in cartilages.

Low levels of the indispensable trace element selenium (Se) can cause oxidative stress and disrupt environmental homeostasis in humans and animals. Selenoprotein S (Selenos), of which Se is a key component, is a member of the selenoprotein family involved in various biological processes. This study aimed to investigate whether low-level SELENOS gene expression can induce oxidative stress and decrease the antioxidative capacity of chondrocytes. Compared with control cells, SELENOS-knockdown ATDC5 cells showed substantially higher dihydroethidium, reactive oxygen species and malondialdehyde levels, and lower superoxide dismutase (SOD) expression. Knockout of the gene in C57BL/6 mice increased the 8-hydroxy-2-deoxyguanosine level considerably and decreased SOD expression in cartilages relative to the levels in wild-type mice. The results showed that the increased nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling mediated by low-level SELENOS expression was involved in oxidative damage. The proliferative zone of the cartilage growth plate of SELENOS-knockout mice was shortened, suggesting cartilage differentiation dysfunction. In conclusion, this study confirmed that low-level Selenos expression plays a role in oxidative stress in cartilages.

Prevalence and incidence of skin tear in older adults：A systematic review and meta-analysis.

BACKGROUND: Skin tear (ST) is a public health problem in older adults; they substantially increase the risk of complications and cause serious adverse consequences and health care burden. AIM: To estimate the pooled prevalence and incidence of ST among older adults. METHODS: Ten databases were systematically searched from their inception to July 27, 2023. Two researchers performed a systematic review independently according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All inconsistencies were resolved by a principal researcher. The pooled prevalence and incidence of ST were estimated in R 4.3.1 program. RESULTS: Thirteen studies were included in this review. The pooled prevalence of ST was 6.0 % (95 % confidence interval (CI): 3.0%-11.0 %, I2 = 98 %), and the pooled incidence was 11.0 % (95 % CI: 5.0%-19.0 %, I2 = 94 %). The prevalence of ST was 11.0 % (95 % CI: 5.0%-19.0 %, I2 = 95 %) in long-term care facilities, 5.0 % (95 % CI: 3.0%-9.0 %, I2 = 86 %) in Europe, and 7.0 % (95 % CI: 1.0%-16.0 %, I2 = 82 %) in the Skin Tear Audit Research classification system (STAR). It has stabilized at 6.0 % since 2021. The incidence of ST was 15.0 % (95 % CI: 11.0%-20.0 %, I2 = 66 %) in long-term care facilities in Japan and 4.0 % (95 % CI: 2.0%-6.0 %) in Canada. CONCLUSIONS: Older adults are at a high risk for ST. Our findings emphasize the importance of epidemiologic studies and further exploring assessment tools for ST. Healthcare professionals should pay attention to ST, identify high-risk individuals and associated factors, and implement targeted prevention strategies for older adults.

Two doses of fosaprepitant included prophylactic treatment for the three-day cisplatin-based chemotherapy induced nausea and vomiting.

PURPOSE: Neurokinin 1 receptor antagonists included prophylactic treatment was recommended for patients who receive one-day cisplatin chemotherapy. It is unclear whether the prolonged administration of fosaprepitant is effective for three-day cisplatin-based chemotherapy induced nausea and vomiting (CINV). We aim to explore the prophylactic antiemetic efficacy and safety of two doses of fosaprepitant included regimen in the patients receiving multiple-day cisplatin chemotherapy. METHODS: This randomized, parallel-group, open-labelled study was conducted in nine hospitals between February 2021 and February 2023. Patients diagnosed as lung cancer and chemotherapy naive were screened. Eligible participants were scheduled to be treated with highly emetogenic chemotherapy regimen which including three days of cisplatin. Then they were randomly divided into the experimental group (two doses of fosaprepitant, Group 2DF) and the control group (one dose of fosaprepitant, Group C). The primary endpoints included the safety and the average none CINV days (NCDs). This study was registered on the website of chictr.org.cn, number ChiCTR2100042665. RESULTS: Overall, 204 participants were randomly assigned, and 198 patients were analyzed. No statistical difference in adverse events was found between the two groups. All treatment-related adverse effects for fosaprepitant observed were of grade 1-2. The average NCDs of Group 2DF was significantly more than Group C (18.21 ± 3.40 days vs 16.14 ± 5.20 days, P = 0.001). Furthermore, the better life function score was achieved in Group 2DF according to FLIE questionnaire. CONCLUSION: The administration of two-dose fosaprepitant was safe and more effective than one dose in protecting patients from CINV induced by three-day cisplatin included chemotherapy.

MicroRNA-206 as a potential cholesterol-lowering drug is superior to statins in mice.

Hypercholesterolemia is frequently intertwined with hepatosteatosis, hypertriglyceridemia, and hyperglycemia. This study is designed to assess the therapeutic efficacy of miR-206 in contrast to statins in the context of managing hypercholesterolemia in mice. We previously showed that miR-206 is a potent inhibitor of de novo lipogenesis (DNL), cholesterol synthesis, and gluconeogenesis in mice. Given that these processes occur within hepatocytes, we employed a mini-circle (MC) system to deliver miR-206 specifically to hepatocytes (designated as MC-miR-206). A single intravenous injection of MC-miR-206 maintained high levels of miR-206 in the liver for at least two weeks, thereby maintaining suppression of hepatic DNL, cholesterol synthesis, and gluconeogenesis. MC-miR-206 significantly reduced DNA damage, endoplasmic reticulum and oxidative stress, and hepatic toxicity. Therapeutically, both MC-miR-206 and statins significantly reduced total serum cholesterol and triglycerides as well as LDL cholesterol and VLDL cholesterol in mice maintained on the normal chow and high-fat high-cholesterol diet. MC-miR-206 reduced liver weight, hepatic triglycerides and cholesterol, and blood glucose, while statins slightly increased hepatic cholesterol and blood glucose and failed to affect levels of liver weight and hepatic triglycerides. Mechanistically, miR-206 alleviated hypercholesterolemia by inhibiting hepatic cholesterol synthesis, while statins increased HMGCR activity, hepatic cholesterol synthesis, and fecal-neutral steroid excretion. MiR-206 facilitates the regression of hypercholesterolemia, hypertriglyceridemia, hyperglycemia, and hepatosteatosis. MiR-206 outperforms statins by reducing hyperglycemia, hepatic cholesterol levels, and hepatic toxicity.

Comparative transcriptomics revealed neurodevelopmental impairments and ferroptosis induced by extremely small iron oxide nanoparticles.

Iron oxide nanoparticles are a type of nanomaterial composed of iron oxide (Fe3O4 or Fe2O3) and have a wide range of applications in magnetic resonance imaging. Compared to iron oxide nanoparticles, extremely small iron oxide nanoparticles (ESIONPs) (∼3 nm in diameter) can improve the imaging performance due to a smaller size. However, there are currently no reports on the potential toxic effects of ESIONPs on the human body. In this study, we applied ESIONPs to a zebrafish model and performed weighted gene co-expression network analysis (WGCNA) on differentially expressed genes (DEGs) in zebrafish embryos of 48 hpf, 72 hpf, 96 hpf, and 120 hpf using RNA-seq technology. The key hub genes related to neurotoxicity and ferroptosis were identified, and further experiments also demonstrated that ESIONPs impaired the neuronal and muscle development of zebrafish, and induced ferroptosis, leading to oxidative stress, cell apoptosis, and inflammatory response. Here, for the first time, we analyzed the potential toxic effects of ESIONPs through WGCNA. Our studies indicate that ESIONPs might have neurotoxicity and could induce ferroptosis, while abnormal accumulation of iron ions might increase the risk of early degenerative neurological diseases.

SUMO-specific peptidase 3 mediates the SUMO3 modification of BECN1 to repress cell autophagy in gliomas.

OBJECTIVE: SUMO Specific Peptidase 3 (SENP3) is involved in the occurrence and development of various cancers. However, its effects on gliomas have been barely reported. Herein, this research was designed to probe the potential mechanisms of SENP3 mediating beclin-1(BECN1) SUMO3 modification in autophagy in gliomas. METHODS: SENP3 expression in gliomas was analyzed through bioinformatic information. Clinical samples of glioma tissues were collected and frozen. SENP3 expression was evaluated with western blot. In glioma cells, autophagy- and apoptosis-related proteins, viability, and apoptosis were assessed with western blot and immunofluorescence, the cell counting kit-8, and flow cytometry, respectively. The SUMO modification of BECN1 and interactions between BECN1 and PIK3C3 were identified with Ni-NTA pull-down and co-immunoprecipitation assays, respectively. The tumor formation assay was carried out in nude mice for in vivo validation. RESULTS: Bioinformatics analysis predicted the overexpression of SENP3 in gliomas, which was confirmed in clinical samples and glioma cells. SENP3 silencing promoted autophagy and apoptosis and inhibited viability in glioma cells, which was counteracted by further autophagy inhibition. Mechanistically, SENP3 facilitated BECN1 deSUMOylation to mediate the SUMO3 modification of BECN1, thus impeding the formation of BECN1-PIK3C3 complexes. The loss of the SUMO part in BECN1 lowered the protein expression of LC3 and the value of LC3BII/LC3BI in glioma cells. Additionally, SENP3 silencing boosted autophagy and repressed tumor growth in mice, which was neutralized by further autophagy repression. CONCLUSION: SENP3 fosters the deSUMOylation of BECN1 to block the formation of BECN1-PIK3C3 complexes, thus restraining glioma cell autophagy.

Research and Design of Energy-Harvesting System Based on Macro Fiber Composite Cantilever Beam Applied in Low-Frequency and Low-Speed Water Flow.

In nature, lakes and water channels offer abundant underwater energy sources. However, effectively harnessing these green and sustainable underwater energy sources is challenging due to their low flow velocities. Here, we propose an underwater energy-harvesting system based on a cylindrical bluff body and a cantilever beam composed of a macro fiber composite (MFC), taking advantage of the MFC's low-frequency, lightweight, and high piezoelectric properties to achieve energy harvesting in low-frequency and low-speed water flows. When a water flow impacts the cylindrical bluff body, it generates vibration-enhanced and low-frequency vortices behind the bluff body. The optimized diameter of the bluff body and the distance between the bluff body and the MFC were determined using finite element analysis software, specifically COMSOL. According to the simulation results, an energy-harvesting system based on an MFC cantilever beam applied in a low-frequency and low-speed water flow was designed and prepared. When the diameter of the bluff body was 25 mm, and the distance between the bluff body and MFC was 10 mm and the maximum output voltage was 22.73 V; the power density could reach 0.55 mW/cm2 after matching the appropriate load. The simulation results and experimental findings of this study provide valuable references for designing and investigating energy-harvesting systems applied in low-frequency and low-speed water flows.

Frequency-Specific Alterations of Fractional Amplitude of Low-Frequency Fluctuations in Adult-Onset Hypothyroidism.

BACKGROUND: The neuropathophysiological mechanisms of brain damage underlying hypothyroidism remain unclear. Fractional amplitude of low-frequency fluctuations (fALFF) has been established as a reliable indicator for investigation of abnormal spontaneous brain activity that occurs at specific frequencies in different types of mental disorder. However, the changes of fALFF in specific frequency bands in hypothyroidism have not yet been investigated. METHODS: Fifty-three hypothyroid patients and 39 healthy controls (HCs) underwent thyroid-related hormone levels tests, neuropsychological assessment, and magnetic resonance imaging (MRI) scans. The fALFF in the standard band (0.01-0.1 Hz), slow-4 (0.027-0.073 Hz), and slow-5 bands (0.01-0.027 Hz) were analyzed. An analysis of Pearson correlation was conducted between fALFF, thyroid-related hormone levels, and neuropsychological scores in hypothyroid patients. RESULTS: Compared to HCs, within the routine band, hypothyroidism group showed significantly decreased fALFF in left lingual gyrus, middle temporal gyrus (MTG), precentral gyrus, calcarine cortex, and right inferior occipital gyrus; within the slow-5 band, the hypothyroidism group exhibited decreased fALFF in left lingual gyrus, MTG, superior temporal gyrus, postcentral gyrus, and paracentral lobule, and increased fALFF in supplementary motor area (SMA) and right middle frontal gyrus; additionally, fALFF in the left lingual gyrus within the routine and slow-5 bands were negatively correlated with the level of thyroid stimulating hormone. CONCLUSIONS: In this study, the slow-5 frequency band exhibits better sensitivity than the standard band in detecting fALFF values. A decrease of fALFF values in the lingual gyrus and MTG was observed in both the standard and slow-5 bands and might present potential neuroimaging biomarkers for hypothyroidism. CLINICAL TRIAL REGISTRATION: No: ChiCTR2000028966. Registered 9 January, 2020, https://www.chictr.org.cn.

Aversatile MOF as an electrochemical/fluorescence/colorimetric signal probe for the tri-modal detection of MMP-9 secretion in the extracellular matrix to identify the efficacy of chemotherapeutic drugs.

BACKGROUND: MMP-9 plays a crucial role in regulating the degradation of proteins within the extracellular matrix (ECM). This process closely correlates with the occurrence, development, invasion, and metastasis of various tumors, each exhibiting diverse levels of MMP-9 expression. However, the accuracy of detection results using the single-mode method is compromised due to the coexistence of multiple biologically active substances in the ECM. RESULTS: Therefore, in this study, a tri-modal detection system is proposed to obtain more accurate information by cross-verifying the results. Herein, we developed a tri-modal assay using the ZIF-8@Au NPs@S QDs composite as a multifunctional signal probe, decorated with DNA for the specific capture of MMP9. Notably, the probe demonstrated high conductivity, fluorescence response and mimicked enzyme catalytic activity. The capture segments of hybrid DNA specifically bind to MMP9 in the presence of MMP9, causing the signal probe to effortlessly detach the sensor interface onto the sample solution. Consequently, the sensor current performance is weakened, with the colorimetric and fluorescent signals becoming stronger with increasing MMP9 concentration. Notably, the detection range of the tri-modal sensor platform spans over 10 orders of magnitude, verifying notable observations of MMP-9 secretion in four tumor cell lines with chemotherapeutic drugs. Furthermore, the reliability of the detection results can be enhanced by employing pairwise comparative analysis. SIGNIFICANCE: This paper presents an effective strategy for detecting MMP9, which can be utilized for both the assessment of MMP-9 in cell lines and for analyzing the activity and mechanisms involved in various tumors.

Pickering emulsion stabilization with colloidal lignin is enhanced by salt-induced networking in the aqueous phase.

We study the effect of electrolytes on the stability in aqueous media of spherical lignin particles (LP) and its relevance to Pickering emulsion stabilization. Factors considered included the role of ionic strength on morphology development, LP size distribution, surface charge, interfacial adsorption, colloidal and wetting behaviors. Stable emulsions are formed at salt concentrations as low as 50 mM, with the highest stability observed at a critical concentration (400 mM). We show salt-induced destabilization of LP aqueous dispersions at an ionic strength >400 mM. At this critical concentration LP flocculation takes place and particulate networks are formed. This has a profound consequence on the stability of LP-stabilized Pickering emulsions, affecting rheology and long-term stability. The results along with quartz microgravimetry and confocal microscopy observations suggest a possible mechanism for stabilization that considers the interfacial adsorption of LP at oil/water interfaces. The often-unwanted colloidal LP destabilization in water ensues remarkably stable Pickering emulsions by the effect of network formation.

Age-related changes of dopamine D1 and D2 receptors expression in parvalbumin-positive cells of the orbitofrontal and prelimbic cortices of mice.

Dopamine (DA) plays a pivotal role in reward processing, cognitive functions, and emotional regulation. The prefrontal cortex (PFC) is a critical brain region for these processes. Parvalbumin-positive (PV+) neurons are one of the major classes of inhibitory GABAergic neurons in the cortex, they modulate the activity of neighboring neurons, influencing various brain functions. While DA receptor expression exhibits age-related changes, the age-related changes of these receptors in PV+ neurons, especially in the PFC, remain unclear. To address this, we investigated the expression of DA D1 (D1R) and D2 (D2R) receptors in PV+ neurons within the orbitofrontal (OFC) and prelimbic (PrL) cortices at different postnatal ages (P28, P42, P56, and P365). We found that the expression of D1R and D2R in PV+ neurons showed both age- and region-related changes. PV+ neurons in the OFC expressed a higher abundance of D1 than those in the PrL, and those neurons in the OFC also showed higher co-expression of D1R and D2R than those in the PrL. In the OFC and PrL, D1R in PV+ neurons increased from P28 and reached a plateau at P42, then receded to express at P365. Meanwhile, D2R did not show significant age-related changes between the two regions except at P56. These results showed dopamine receptors in the prefrontal cortex exhibit age- and region-specific changes, which may contribute to the difference of these brain regions in reward-related brain functions.

Characterize direct protein interactions with enrichable, cleavable and latent bioreactive unnatural amino acids.

Latent bioreactive unnatural amino acids (Uaas) have been widely used in the development of covalent drugs and identification of protein interactors, such as proteins, DNA, RNA and carbohydrates. However, it is challenging to perform high-throughput identification of Uaa cross-linking products due to the complexities of protein samples and the data analysis processes. Enrichable Uaas can effectively reduce the complexities of protein samples and simplify data analysis, but few cross-linked peptides were identified from mammalian cell samples with these Uaas. Here we develop an enrichable and multiple amino acids reactive Uaa, eFSY, and demonstrate that eFSY is MS cleavable when eFSY-Lys and eFSY-His are the cross-linking products. An identification software, AixUaa is developed to decipher eFSY mass cleavable data. We systematically identify direct interactomes of Thioredoxin 1 (Trx1) and Selenoprotein M (SELM) with eFSY and AixUaa.

Facile Preparation of Magnetically Separable Fe3O4/ZnO Nanocomposite with Enhanced Photocatalytic Activity for Degradation of Rhodamine B.

Magnetic separation of photocatalysts holds great promise for water treatment. A magnetic separation method has a positive effect on the recovery of catalysts after degradation. In this paper, an efficient and reusable catalytic system is developed based on coating magnetic Fe3O4 by depositing Fe2+ on the surface of ZnO. The Fe3O4/ZnO nanocomposite exhibits enhanced performance for organic pollutant degradation. The Fe3O4/ZnO system demonstrates a high photocatalytic activity of 100% degradation efficiency in Rhodamine B (RhB) degradation under UV light irradiation for 50 min. The excellent photocatalytic activity is primarily due to the separation of photogenerated electron-hole pairs being facilitated by the strong interaction between Fe3O4 and ZnO. The induction of the magnetic Fe3O4 endows the Fe3O4/ZnO composite with superior magnetic separation capability from water. Experiments with different radical scavengers revealed that the hydroxyl radical (·OH) is the key reactive radical for the effective degradation of RhB. This work innovatively affords a common interfacial dopant deposition strategy for catalytic application in the degradation of organic dye pollutants and catalyst separation from wastewater efficiently.

[Spatiotemporal Simulation and Prediction of Soil Organic Carbon Density in Gannan Grassland Under Future Climate Scenarios].

To study the temporal and spatial distribution characteristics of soil organic carbon density in grassland and explore the relationship between organic carbon density and influencing factors is of great significance to the management and maintenance of grassland ecosystems in Gannan Autonomous Prefecture, which is conducive to realizing the goal of "double carbon," promoting carbon sink, and mitigating climate change. Taking Gannan Tibetan Autonomous Prefecture of Gansu Province as the research object, based on data from two CMIP6 future climate scenarios (SSP126 and SSP585), the CENTURY model was used to simulate and predict the temporal and spatial changes in soil organic carbon density in grassland of Gannan during 2023-2100. The main conclusions were as follows:① From 2023 to 2100, total organic carbon density, slow organic carbon density, and inert organic carbon density all showed a downward trend, whereas active organic carbon density fluctuated first and then increased. Meanwhile, the total organic carbon density, active organic carbon density, slow organic carbon density, and inert organic carbon density under the SSP585 scenario were higher than those under the SSP126 scenario. ② Mann-Kendall mutation analysis showed that the abrupt change in the difference of soil total organic carbon density (Δsomtc) occurred in 2030. The abrupt change in the difference of soil active carbon density (Δsom1c) occurred in 2027. ③ During the study period, the average soil organic carbon density of Gannan grassland was 7 505.69 g·m-2 under the SSP126 scenario and 7 551.87 g·m-2 under the SSP585 scenario. Gannan grassland soil organic carbon density was higher in the west and lower in the east, and the coefficient of variation was relatively stable. ④ The results of partial correlation analysis showed that precipitation was positively correlated with soil organic carbon density, whereas temperature was significantly negatively correlated with soil organic carbon density under future climate scenarios. ⑤ The results of the Theil-Sen Median trend analysis and Mann-Kendall test showed that under the two climate scenarios, the soil organic carbon density in Gannan showed an overall downward trend, in which Luqu County showed the fastest downward trend and Dibe County showed the slowest.

Quorum-Sensing Signal DSF Inhibits the Proliferation of Intestinal Pathogenic Bacteria and Alleviates Inflammatory Response to Suppress DSS-Induced Colitis in Zebrafish.

The imbalance of gut microbiota is an important factor leading to inflammatory bowel disease (IBD). Diffusible signal factor (DSF) is a novel quorum-sensing signal that regulates bacterial growth, metabolism, pathogenicity, and host immune response. This study aimed to explore the therapeutic effect and underlying mechanisms of DSF in a zebrafish colitis model induced by sodium dextran sulfate (DSS). The results showed that intake of DSF can significantly improve intestinal symptoms in the zebrafish colitis model, including ameliorating the shortening of the intestine, reducing the increase in the goblet cell number, and restoring intestinal pathological damage. DSF inhibited the upregulation of inflammation-related genes and promoted the expression of claudin1 and occludin1 to protect the tightness of intestinal tissue. The gut microbiome analysis demonstrated that DSF treatment helped the gut microbiota of the zebrafish colitis model recover to normal at the phylum and genus levels, especially in terms of pathogenic bacteria; DSF treatment downregulated the relative abundance of Aeromonas hydrophila and Staphylococcus aureus, and it was confirmed in microbiological experiments that DSF could effectively inhibit the colonization and infection of these two pathogens in the intestine. This study suggests that DSF can alleviate colitis by inhibiting the proliferation of intestinal pathogens and inflammatory responses in the intestine. Therefore, DSF has the potential to become a dietary supplement that assists in the antibiotic and nutritional treatment of IBD.

Hippocampal transcriptome-wide association study and pathway analysis of mitochondrial solute carriers in Alzheimer's disease.

The etiopathogenesis of late-onset Alzheimer's disease (AD) is increasingly recognized as the result of the combination of the aging process, toxic proteins, brain dysmetabolism, and genetic risks. Although the role of mitochondrial dysfunction in the pathogenesis of AD has been well-appreciated, the interaction between mitochondrial function and genetic variability in promoting dementia is still poorly understood. In this study, by tissue-specific transcriptome-wide association study (TWAS) and further meta-analysis, we examined the genetic association between mitochondrial solute carrier family (SLC25) genes and AD in three independent cohorts and identified three AD-susceptibility genes, including SLC25A10, SLC25A17, and SLC25A22. Integrative analysis using neuroimaging data and hippocampal TWAS-predicted gene expression of the three susceptibility genes showed an inverse correlation of SLC25A22 with hippocampal atrophy rate in AD patients, which outweighed the impacts of sex, age, and apolipoprotein E4 (ApoE4). Furthermore, SLC25A22 downregulation demonstrated an association with AD onset, as compared with the other two transcriptome-wide significant genes. Pathway and network analysis related hippocampal SLC25A22 downregulation to defects in neuronal function and development, echoing the enrichment of SLC25A22 expression in human glutamatergic neurons. The most parsimonious interpretation of the results is that we have identified AD-susceptibility genes in the SLC25 family through the prediction of hippocampal gene expression. Moreover, our findings mechanistically yield insight into the mitochondrial cascade hypothesis of AD and pave the way for the future development of diagnostic tools for the early prevention of AD from a perspective of precision medicine by targeting the mitochondria-related genes.