Gut microbiota, circulating cytokines and dementia: a Mendelian randomization study.

BACKGROUND: Some studies have shown that gut microbiota may be associated with dementia. However, the causal effects between gut microbiota and different types of dementia and whether cytokines act as a mediator remain unclear. METHODS: Gut microbiota, cytokines, and five dementia types, including Alzheimer's disease (AD), frontotemporal dementia (FTD), dementia with Lewy body (DLB), vascular dementia (VD), and Parkinson's disease dementia (PDD) were identified from large-scale genome-wide association studies (GWAS) summary data. We used Mendelian randomization (MR) to investigate the causal relationships between gut microbiota, cytokines, and five types of dementia. Inverse variance weighting (IVW) was used as the main statistical method. In addition, we explored whether cytokines act as a mediating factor in the pathway from gut microbiota to dementia. RESULTS: There were 20 positive and 16 negative causal effects between genetic liability in the gut microbiota and dementia. Also, there were five positive and four negative causal effects between cytokines and dementias. Cytokines did not act as mediating factors. CONCLUSIONS: Gut microbiota and cytokines were causally associated with five types of dementia, and cytokines seemed not to be the mediating factors in the pathway from gut microbiota to dementia.

Regulatory mucosa-associated invariant T cells controlled by ß1 adrenergic receptor signaling contribute to hepatocellular carcinoma progression.

BACKGROUND AND AIMS: The innate-like mucosa-associated invariant T (MAIT) cells are enriched in human liver and have been linked to human HCC. However, their contributions to the progression of HCC are controversial due to the heterogeneity of MAIT cells, and new MAIT cell subsets remain to be explored. APPROACH AND RESULTS: Combining single cell RNA sequencing (scRNA-seq) and flow cytometry analysis, we performed phenotypic and functional studies and found that FOXP3 + CXCR3 + MAIT cells in HCC patients were regulatory MAIT cells (MAITregs) with high immunosuppressive potential. These MAITregs were induced under Treg-inducing condition and predominantly from FOXP3 - CXCR3 + MAIT cells, which displayed mild Treg-related features and represented a pre-MAITreg reservoir. In addition, the induction and function of MAITregs were promoted by ß1 adrenergic receptor signaling in pre-MAITregs and MAITregs, respectively. In HCC patients, high proportion of the intratumoral MAITregs inhibited antitumor immune responses and was associated with poor clinical outcomes. CONCLUSIONS: Together, we reveal an immunosuppressive subset of MAIT cells in HCC patients that contributes to HCC progression, and propose a control through neuroimmune crosstalk.

Afterglow Performance of Phenylenevinylene-Based Semiconducting Polymer Nanoparticles Doped with Photosensitizers Containing Electron-Withdrawing Groups.

It is usually believed that doping with photosensitizers capable of generating singlet oxygen (1O2) plays a pivotal role in enhancing the afterglow performance of semiconducting polymer nanoparticles (SPNs). However, the effect of doping photosensitizer bearing electron-withdrawing groups has not been reported. Here we report the effect of doping with six photosensitizers possessing different electron-withdrawing groups on the afterglow performance of SPNs using poly[(9,9-di(2-ethylhexyl)-9H-fluo-rene-2,7-vinylene)-co-(1-methoxy-4-(2-ethylhexyloxy)-2,5-phenylenevinylene)] (PF-MEHPPV) as substrate. It was found that the afterglow performance of SPNs was significantly influenced by doping with photosensitizers bearing electron-withdrawing groups. For the doped photosensitizers with strong electron-withdrawing groups, the stronger the electron-withdrawing ability of the group, the worse of the afterglow performance of the SPN regardless of the 1O2 generation ability of the photosensitizer. When the doped photosensitizer exhibited weak or none electron-withdrawing effect, the 1O2 generation ability of the photosensitizer played a dominant role on the afterglow performance of the SPNs. This work deepens the understanding of the design and synthesis of SPNs with different afterglow properties.

The role of liver transplantation in COACH syndrome (Joubert syndrome with congenital hepatic fibrosis): A review of the literature.

BACKGROUND: COACH syndrome is a rare autosomal recessive genetic disease characterized by liver fibrosis, which leads to severe complications related to portal hypertension. However, only a few patients with COACH syndrome undergoing liver transplantation (LT) have been reported. MATERIALS AND METHODS: We herein report the outcomes of four children who underwent LT for COACH syndrome at our institute and review three previously reported cases to elucidate the role of LT in COACH syndrome. RESULTS: All four patients in our institute were female, and three received living donors LT. All patients were diagnosed with COACH syndrome by genetic testing. LT was performed in these patients at 3, 7, 9, and 14 years old. The indication for LT was varices related to portal hypertension in all patients. One showed an intrapulmonary shunt. Blood tests revealed renal impairment due to nephronophthisis in three patients, and one developed renal insufficiency after LT. The liver function was maintained in all patients. A literature review revealed detailed information for three more patients. The indication for LT in these three cases was portal hypertension, such as bleeding from esophageal varices. One patient had chronic renal failure on hemodialysis at LT and underwent combined liver and kidney transplantation. Of these three previous patients, one died from hepatic failure due to de novo HCV infection 3 years after LT. CONCLUSIONS: LT should be considered an effective treatment for COACH syndrome in patients with severe portal hypertension. However, a detailed follow-up of the renal function is necessary.

Maternal inulin supplementation ameliorates prenatal methamphetamine exposure-induced hepatotoxicity and restores gut microbiota in mouse offspring.

Prenatal exposure to methamphetamine (METH) is an issue of global concern due to its adverse effects on offspring, particularly its impact on liver health, an area still not fully understood. Inulin, a recognized prebiotic, is thought to potentially ameliorate these developmental disorders and toxic injuries in progeny. To investigate the effects of prenatal METH exposure on the liver and the role of gut microbiota, we established a murine model, the subjects of which were exposed to METH prenatally and subsequently treated with inulin. Our findings indicate that prenatal METH exposure causes liver damage in offspring, as evidenced by a decreased liver index, histopathological changes, diminished glycogen synthesis, hepatic dysfunction, and alterations in mRNA profiles. Furthermore, it impairs the antioxidant system and induces oxidative stress, possibly due to changes in cecal microbiota and dysregulation of bile acid homeostasis. However, maternal inulin supplementation appears to restore the gut microbiota in offspring and mitigate the hepatotoxic effects induced by prenatal METH exposure. Our study provides definitive evidence of METH's transgenerational hepatotoxicity and suggests that maternal inulin supplementation could be an effective preventive strategy.

The gut microbiota contributes to methamphetamine-induced reproductive toxicity in male mice.

Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest that METH can disrupt the gut microbiota. Furthermore, the gut-testis axis concept has gained attention due to the potential link between gut microbiome dysfunction and reproductive health. Nonetheless, the role of the gut microbiota in mediating the impact of METH on male reproductive toxicity remains unclear. In this study, we employed a mouse model exposed to escalating doses of METH to assess sperm quality, testicular pathology, and reproductive hormone levels. The fecal microbiota transplantation method was employed to investigate the effect of gut microbiota on male reproductive toxicity. Transcriptomic, metabolomic, and microbiological analyses were conducted to explore the damage mechanism to the male reproductive system caused by METH. We found that METH exposure led to hormonal disorders, decreased sperm quality, and changes in the gut microbiota and testicular metabolome in mice. Testicular RNA sequencing revealed enrichment of several Gene Ontology terms associated with reproductive processes, as well as PI3K-Akt signaling pathways. FMT conveyed similar reproductive damage from METH-treated mice to healthy recipient mice. The aforementioned findings suggest that the gut microbiota plays a substantial role in facilitating the reproductive toxicity caused by METH, thereby highlighting a prospective avenue for therapeutic intervention in the context of METH-induced infertility.

TgMIF Promotes Hepatocyte Pyroptosis and Recruitment of Proinflammatory Macrophages During Severe Liver Injury in Acute Toxoplasmosis.

Liver injury is a common complication during infection of Toxoplasma gondii. However, the Toxoplasma effector proteins involved remain unknown. Herein, we identified that T. gondii macrophage migration inhibitory factor (TgMIF) is a critical pathogenic factor of liver injury in acute toxoplasmosis mouse model induced by a less virulent strain, which is widely prevalent in humans. We show that TgMIF is a novel activator of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome in hepatocytes, resulting in subsequent pyroptosis. Furthermore, T. gondii promotes the TgMIF-dependent infiltration of Ly6Chi proinflammatory macrophages to release cytokines, leading to hepatocyte apoptosis. Although the intense inflammation induced by TgMIF inhibits the proliferation of intracellular parasites, it results in fatal liver damage. In contrast, parasites with TgMIF gene deletion significantly alleviate liver injury and prolong mice survival. The discovery of novel Toxoplasma virulence factor may expedite the development of human toxoplasmosis control strategies.

CircFOXN2 alleviates glucocorticoid- and tacrolimus-induced dyslipidemia by reducing FASN mRNA stability by binding to PTBP1 during liver transplantation.

We aimed to examine impacts and functional mechanism of circular RNA forkhead box N2 (FOXN2) in tacrolimus (TAC)- and dexamethasone (Dex)-induced lipid metabolism disorders. RNA level and protein contents in TAC, Dex, or combined TAC- plus Dex-treated patients and Huh-7 cells were measured utilizing quantitative real-time (qRT)-PCR and western blotting assays measured the formation of lipid droplet. Total cholesterol (TC) and triglyceride (TG) levels were determined using corresponding commercial kits and Oil red O staining. RNA immunoprecipitation and RNA pull-down verified the binding relationship among circFOXN2, polypyrimidine tract binding protein 1 (PTBP1) and fatty acid synthase (FASN). Male C57BL/6 mice were used to establish a dyslipidemia mouse model to validate the discoveries at the cellular level. Dex treatment significantly promoted TAC-mediated increase of TC and TG in serum samples and Huh-7 cells. Moreover, circFOXN2 was reduced but FASN was elevated in TAC-treated Huh-7 cells, and these expression trends were markedly enhanced by Dex cotreatment. Overexpression of circFOXN2 could reverse the accumulation of TC and TG and the upregulation of FASN and sterol regulatory element binding transcription factor 2 (SREBP2) mediated by Dex and TAC cotreatment. Mechanistically, circFOXN2 reduced FASN mRNA stability by recruiting PTBP1. The protective roles of circFOXN2 overexpression on lipid metabolism disorders were weakened by FASN overexpression. In vivo finding also disclosed that circFOXN2 greatly alleviated the dysregulation of lipid metabolism triggered by TAC plus Dex. CircFOXN2 alleviated the dysregulation of lipid metabolism induced by the combination of TAC and Dex by modulating the PTBP1/FASN axis.NEW & NOTEWORTHY Collectively, our experiments revealed for the first time that circFOXN2 alleviated the Dex- and TAC-induced dysregulation of lipid metabolism by regulating the PTBP1/FASN axis. These findings suggested that circFOXN2 and FASN might be candidate targets for the treatment of Dex- and TAC-induced metabolic disorders.

Effect of raw electroencephalogram-guided anesthesia administration on postoperative outcomes in elderly patients undergoing abdominal major surgery: a randomized controlled trial.

BACKGROUND: EEG monitoring techniques are receiving increasing clinical attention as a common method of reflecting the depth of sedation in the perioperative period. The influence of depth of sedation indices such as the bispectral index (BIS) generated by the processed electroencephalogram (pEEG) machine to guide the management of anesthetic depth of sedation on postoperative outcome remains controversial. This research was designed to decide whether an anesthetic agent exposure determined by raw electroencephalogram (rEEG) can influence anesthetic management and cause different EEG patterns and affect various patient outcomes. METHODS: A total of 141 participants aged ≥ 60 years undergoing abdominal major surgery were randomized to rEEG-guided anesthesia or routine care group. The rEEG-guided anesthesia group had propofol titrated to keep the rEEG waveform at the C-D sedation depth during surgery, while in the routine care group the anesthetist was masked to the patient's rEEG waveform and guided the anesthetic management only through clinical experience. The primary outcome was the presence of postoperative complications, the secondary outcomes included intraoperative anesthetic management and different EEG patterns. RESULTS: There were no statistically significant differences in the occurrence of postoperative respiratory, circulatory, neurological and gastrointestinal complications. Further EEG analysis revealed that lower frontal alpha power was significantly associated with a higher incidence of POD, and that rEEG-guidance not only reduced the duration of deeper anesthesia in patients with lower frontal alpha power, but also allowed patients with higher frontal alpha power to receive deeper and more appropriate depths of anesthesia than in the routine care group. CONCLUSIONS: In elderly patients undergoing major abdominal surgery, rEEG-guided anesthesia did not reduce the incidence of postoperative respiratory, circulatory, neurological and gastrointestinal complications. rEEG-guided anesthesia management reduced the duration of intraoperative BS in patients and the duration of over-deep sedation in patients with lower frontal alpha waves under anesthesia, and there was a strong association between lower frontal alpha power under anesthesia and the development of POD. rEEG-guided anesthesia may improve the prognosis of patients with vulnerable brains by improving the early identification of frail elderly patients and providing them with a more effective individualized anesthetic managements.

Inulin alleviates neuroinflammation and oxidative stress induced by perinatal 2-ethylhexyl diphenyl phosphate (EHDPHP) exposure in female mice and offspring.

Organophosphorus flame retardants (OPFRs), including 2-ethylhexyl diphenyl phosphate (EHDPHP), are prevalent in everyday life due to their broad usage in fields such as healthcare, electronics, industry, and sports. These compounds, added to polymers through physical mixing, can leach into the environment, posing a risk to humans through direct contact or the food chain. Despite known associations with health issues like endocrine disruption, neurotoxicity, and reproductive toxicity, the implications of perinatal EHDPHP exposure on both mothers and offspring are still unclear. This study aimed to investigate the neuroinflammatory effects of EHDPHP and the potential mitigating role of inulin. Pregnant C57 mice were administered either a corn oil control or an EHDPHP solution (300 µg/kg bw/d) from gestation day 7 (GD7) to postnatal day 21 (PND21). Concurrently, mice were provided either regular drinking water or water supplemented with 1% inulin. We found that EHDPHP significantly increased the serum levels of IL-1ß, IL-6, and MDA, but decreased SOD levels in both mothers and pups. These effects were reversed by inulin supplementation. RNA-sequencing revealed that EHDPHP induced inflammation and oxidative stress through the TLR4/NF-κB pathway, which was mitigated by inulin. In conclusion, inulin ameliorated EHDPHP-induced neuroinflammation and oxidative stress in both mothers and offspring, highlighting its potential therapeutic role.

Ratiometric Luminescence Aptasensor Based on Dual-Emissive Persistent Luminescent Nanoparticles for Autofluorescence- and Exogenous Interference-Free Determination of Trace Aflatoxin B1 in Food Samples.

Sensitive and accurate determination of aflatoxin B1 (AFB1) is of great significance to food safety and human health as it is recognized as the most toxic mycotoxin and carcinogenic. Herein, we report a ratiometric luminescence aptasensor based on dual-emissive persistent luminescent nanoparticles (PLNP) for the accurate determination of trace AFB1 in complex food samples without autofluorescence and exogenous interference. Dual-emissive PLNP ZnGa2O4:Cr0.0001 was prepared first and acted as the donor for energy transfer as well as the signal unit with phosphorescence at 714 and 508 nm (the detection and the reference signal, respectively). AFB1 aptamer was then bonded on the surface of PLNP to offer specific recognition ability. Aptamer complementary DNA modified with Cy5.5 was employed as the acceptor for energy transfer and the quenching group to eventually develop a turn-on ratiometric luminescence aptasensor. The developed ratiometric luminescence aptasensor combined the merits of long-lasting luminescence, in situ excitation and autofluorescence-free of PLNP, exogenous interference-free and self-calibration reading of ratiometric sensor, as well as the high selectivity of aptamer, holding great promise for accurate determination of trace AFB1 in complex matrix. The developed ratiometric aptasensor exhibited excellent linearity (0.05-70 ng mL-1), low limit of detection (0.016 ng mL-1), and good precision (2.3% relative standard deviation for 11 replicate determination of 1 ng mL-1 AFB1). The proposed ratiometric aptasensor was successfully applied for the determination of AFB1 in corn, wheat, peanut, millet, oats, and wheat kernels with recoveries of 95.1-106.5%.

Methamphetamine induces intestinal injury by altering gut microbiota and promoting inflammation in mice.

Methamphetamine (METH) is a psychostimulant abused worldwide. Its abuse induces intestinal toxicity. Moreover, the gut microbiota is altered by drugs, which induces intestinal injury. Whether gut microbiota mediates METH-induced intestinal toxicity remains to be validated. In the present study, wild-type and TLR4-/- mice were treated with METH. Gut microbiota was determined using 16S rRNA gene sequencing. Transcriptomics of the intestinal mucosa was performed by RNA-Sequencing. Blood levels of pro-inflammatory cytokines and lipopolysaccharide (LPS), the intestinal barrier, and inflammation were also assessed. METH treatment weakened the intestinal barrier and increased pro-inflammatory cytokines and LPS levels in the blood. Moreover, METH treatment significantly decreased the diversity of probiotics but increased the abundance of pathogenic gut microbiota, contributing to the over-production of LPS and disruption of intestinal barrier. Inflammatory pathways were enriched in the intestinal mucosa of METH-treated mice by KEGG analysis. Consistently, activation of the TLR4 pathway was determined in METH-treated mice, which confirmed intestinal inflammation. However, pretreatment with antibiotics or Tlr4 silencing significantly alleviated METH-induced gut microbiota dysbiosis, LPS over-production, intestinal inflammation, and disruption of the intestinal barrier. These findings suggested that the gut microbiota and LPS-mediated inflammation took an important role in METH-induced intestinal injury. Taken together, these findings suggest that METH-induced intestinal injury is mediated by gut microbiota dysbiosis and LPS-associated inflammation.

Silencing the Tlr4 Gene Alleviates Methamphetamine-Induced Hepatotoxicity by Inhibiting Lipopolysaccharide-Mediated Inflammation in Mice.

Methamphetamine (METH) is a stimulant drug. METH abuse induces hepatotoxicity, although the mechanisms are not well understood. METH-induced hepatotoxicity was regulated by TLR4-mediated inflammation in BALB/c mice in our previous study. To further investigate the underlying mechanisms, the wild-type (C57BL/6) and Tlr4-/- mice were treated with METH. Transcriptomics of the mouse liver was performed via RNA-sequencing. Histopathological changes, serum levels of metabolic enzymes and lipopolysaccharide (LPS), and expression of TLR4-mediated proinflammatory cytokines were assessed. Compared to the control, METH treatment induced obvious histopathological changes and significantly increased the levels of metabolic enzymes in wild-type mice. Furthermore, inflammatory pathways were enriched in the liver of METH-treated mice, as demonstrated by expression analysis of RNA-sequencing data. Consistently, the expression of TLR4 pathway members was significantly increased by METH treatment. In addition, increased serum LPS levels in METH-treated mice indicated overproduction of LPS and gut microbiota dysbiosis. However, antibiotic pretreatment or silencing Tlr4 significantly decreased METH-induced hepatic injury, serum LPS levels, and inflammation. In addition, the dampening effects of silencing Tlr4 on inflammatory pathways were verified by the enrichment analysis of RNA-sequencing data in METH-treated Tlr4-/- mice compared to METH-treated wild-type mice. Taken together, these findings implied that Tlr4 silencing, comparable to antibiotic pretreatment, effectively alleviated METH-induced hepatotoxicity by inhibiting LPS-TLR4-mediated inflammation in the liver.

mRNA microarray analysis for the identification of potential biomarkers for vital reaction in burned skin: a preliminary pilot study.

The identification of ante- and post-mortem burns is challenging in forensic pathology. In this study, microarray analysis was used to detect the mRNA expression profiles in the skin of an experimental burn mouse model; the results were validated using RT-qPCR. Differentially expressed mRNAs (DE-mRNAs) were assessed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Our results revealed that mRNA expression of 501 genes was significantly different, of which 273 were upregulated and 228 were downregulated in ante-mortem burned mice skin. The expression levels of eight random mRNAs were consistent when measured using the microarray assay-based method and RT-qPCR. Genes from different functional categories and signalling pathways were enriched, including interleukin-20 binding, type IV hypersensitivity, negative regulation of acute inflammatory response, sensory organ development, endocytosis, neuroactive ligand-receptor interaction, and Jak-STAT signalling pathway. Only five of the eight mRNAs exhibited consistent changes in expression between burned skin samples of mice and human autopsy specimens. Our findings showed that DE-mRNAs revealed using microarray are potential biomarkers of ante-mortem burns. However, DE-mRNAs identified from experimental animal models cannot be directly extended to autopsy specimens without careful validation.

Emerging role of RNF2 in cancer: From bench to bedside.

RNF2 (also known as ding, Ring1B or Ring2) is a member of the Ring finger protein family, which functions as E3 ubiquitin ligase for monoubiquitination of histone H2A at lysine 119 (H2AK119ub). RNF2 gene is located at the 1q25.3 site of human chromosome and the coding region is composed of 9 exons, encoding 336 amino acids in total. Many studies have demonstrated that overexpressed RNF2 was involved in the pathological progression of multiple cancers and has an impact on their clinical features. For instance, the upregulated expression level of RNF2 is positively correlated with the occurrence and progression of hepatocellular carcinoma, melanoma, prostate cancer, breast cancer, pancreatic cancer, gastric cancer, and bladder urothelial carcinoma, as well as with the radioresistance of lung cancer and chemoresistance of ovarian cancer. This review provides an up-to-date perspective on the relationship between RNF2 and several cancers and highlights recent studies on RNF2 regulation. In particular, the relevant cellular signaling pathways and potential clinical value of RNF2 in cancers are also discussed, suggesting its potential as an epigenetic biomarker and therapeutic target for these cancers.

Functionalized Persistent Luminescence Nanoparticle-Based Aptasensor for Autofluorescence-free Determination of Kanamycin in Food Samples.

Selective and sensitive determination of trace kanamycin in complex food samples is of great importance for food safety because of its high toxicity. Here, we report a sensitive and autofluorescence-free persistent luminescence (PL) aptasensor for selective, sensitive, and autofluorescence-free determination of kanamycin in food samples. The aptamer for kanamycin was first conjugated onto the surface of magnetic nanoparticles Fe3O4 to serve as the recognition unit as well as the separation element, while the PL nanoparticles ZnGa2O4:Cr (PLNPs) were functionalized with the aptamer complementary DNA (cDNA) as the PL signal. The PL aptasensor consisted of the aptamer-conjugated MNPs (MNPs-apt) and cDNA-functionalized PLNPs (PLNPs-cDNA) and combined the merits of the long-lasting luminescence of PLNPs, the magnetic separation ability of MNPs as well as the selectivity of the aptamer, offering a promising approach for autofluorescence-free determination of kanamycin in food samples. The proposed aptasensor showed excellent linearity in the range from 1 pg mL-1 to 5 ng mL-1 with a limit of detection of 0.32 pg mL-1. The precision for 11 replicate determinations of 100 pg mL-1 kanamycin was 3.1% (relative standard deviation). The developed aptasensor was applied for the determination of kanamycin in milk and honey samples with the recoveries of 95.4-106.3%. The proposed aptasensor is easily extendable to other analytes by simply replacing the aptamer, showing great potential as a universal aptasensor platform for selective, sensitive, and autofluorescence-free detection of hazardous analytes in food samples.

Dual-Emissive Persistent Luminescence Nanoparticle-Based Charge-Reversible Intelligent Nanoprobe for Persistent Luminescence-Ratio Bioimaging along with Chemo-Photothermal Synergic Therapy.

Persistent luminescence nanoparticles (PLNPs) hold great promise for bioimaging owing to no demand for in situ excitation and negligible tissue autofluorescence interference. Nevertheless, huge challenges remain in the further development of single-emissive PLNPs due to the great variation of luminescence with time after excitation ceases. Herein, we report the controllable fabrication of dual-emissive monodispersed PLNPs (ZnGa2O4:Cr) by a surfactant-assisted hydrothermal method in combination with postcalcination for bioimaging. The prepared PLNPs emit luminescence at 508 and 714 nm with a constant luminescence ratio (I508/I714) for more than 1 h after UV excitation stops. Moreover, the prepared PLNPs give a constant I508/I714 ratio signal after repeated excitation by a LED lamp, allowing luminescence ratio imaging to ensure the long-term accuracy for in vivo imaging. In vivo ratio imaging demonstrates the potential of the prepared PLNPs for precision bioimaging. In addition, the prepared PLNPs have been applied to fabricate a theranostic nanoprobe with intelligent tumor-targeted imaging and chemo-photothermal synergistic therapy to further reveal their unique advantage for imaging guided therapy. We believe that the dual-emissive PLNPs will provide a promising nanoplatform for bioimaging and biomedical applications.

Global proteome profiling of human livers upon ischemia/reperfusion treatment.

Hepatic ischemia/reperfusion (I/R) injury represents a major risk factor for liver transplantation and is related to graft dysfunction and acute/chronic rejection. However, a significant part of these processes remain poorly characterized. To reveal differences in the proteome during liver I/R injury, we collected human liver biopsy samples during hepatectomy before and after the Pringle maneuver and conducted a TMT-based proteomic analysis through quantitative high-throughput mass spectrometry. We used a fold-change threshold of 1.3 and a t-test p-value < 0.05 as the criteria to identify 5,257 total quantifiable proteins. The levels of 142 proteins were increased, while the levels of 103 proteins were decreased in response to hepatic I/R treatment. Bioinformatic analysis further revealed that these differentially expressed proteins are mainly involved in multiple biological functions and enzyme-regulated metabolic pathways. Most proteins whose expression was changed are related to the defense, immune and inflammatory responses as well as lipid and steroid metabolic processes. Based on this finding, we developed a panel for targeted proteomic analysis and used the parallel reaction monitoring (PRM) method, qPCR and western blotting experiments to validate alterations in the expression of some of the identified proteins. The upregulated proteins were found to be involved in immunity and inflammatory responses, and downregulated proteins were enriched in metabolic pathways. This study therefore may provide a research direction for the design of new therapeutic strategies for hepatic ischemia/reperfusion injury.

Effect of Topology on Photodynamic Sterilization of Porphyrinic Metal-Organic Frameworks.

Porphyrinic metal-organic frameworks (MOFs) are promising photosensitizers due to the lack of self-aggregation of porphyrin in aqueous solution. However, how the topology of porphyrinic MOFs affects the generation of singlet oxygen (1 O2 ) is unclear. Here, the effect of the topology of porphyrinic MOFs on their photodynamic performance is reported. Four porphyrinic zirconium MOFs (MOF-525, MOF-545, PCN-223 and PCN-224 with different topologies: ftw, csq, shp and she, respectively) were selected to study the influence of topology on the photodynamic antibacterial performance. The 1 O2 generation and the photodynamic antibacterial performance followed an decreasing order of MOF-545>MOF-525>PCN-224>PCN-223. The results reveal that the pore size, the distance between porphyrin, and the number of porphyrin per Zr6 O8 cluster in MOFs greatly affected 1 O2 generation. This work provides guidance for designing new MOFs for efficient photodynamic sterilization.

Electroencephalographic dynamics of etomidate-induced loss of consciousness.

BACKGROUND: Highly structured electroencephalography (EEG) oscillations can occur in adults during etomidate-induced general anesthesia, but the link between these two phenomena is poorly understood. Therefore, in the present study, we investigated the electroencephalogram dynamics of etomidate-induced loss of consciousness (LOC) in order to understand the neurological mechanism of etomidate-induced LOC. METHODS: This study is a prospective observational study. Etomidate-induced anesthesia was performed on eligible patients undergoing elective surgery. We analyzed EEG data from 20 patients who received etomidate for the induction of general anesthesia. We used power spectra and coherence methods to process and analyze the EEG data. Our study was based on 4-channel EEG recordings. RESULTS: Compared with the baseline (awake period), etomidate induced an increase in power in delta, theta, alpha and beta waves during LOC. Compared with the awake period, the delta-wave (1-4 Hz), alpha-wave(8-13 Hz), and theta-wave(4-8 Hz) coherence increased significantly during LOC, while the slow-wave (< 1 Hz) coherence decreased. However, the delta wave (1.0-4.0 Hz) during etomidate-induced LOC was more coherent than during the awake period (1.86-3.17 Hz, two-group test for coherence, p < 0.001). CONCLUSIONS: The neural circuit mechanism of etomidate-induced LOC is closely related to the induction of oscillation in delta, theta, alpha and beta waves and the enhancement of delta-wave coherence. TRIAL REGISTRATION: ChiCTR1800017110.