The Influence of the Gut Microbiota on Alzheimer's Disease: A Narrative Review.

Alzheimer's disease (AD) is a common neurodegenerative disease that tends to occur in the elderly. The main symptom is hypomnesia. More and more older people are suffering from this disease worldwide. By 2050, 152 million people worldwide are expected to have AD. It is thought that the aggregation of amyloid-beta peptides and hyper-phosphorylated tau tangles contribute to AD. The microbiota-gut-brain (MGB) axis appears as a new concept. The MGB axis is a collection of microbial molecules produced in the gastrointestinal tract that influence the physiological function of the brain. In this review, we discuss how the gut microbiota (GM) and its metabolites affect AD in different ways. Dysregulation of the GM has been shown to be involved in various mechanisms involved in memory and learning functions. We review the current literature on the role of the entero-brain axis in the pathogenesis of AD and its potential role as a future therapeutic target in the treatment and/or prevention of AD.

Fate of iron nanoparticles in anammox system: Dissolution, migration and transformation.

Iron nanoparticles (FeNPs) are commonly used in various industrial processes, leading to their release into the environment and eventual entrance into wastewater treatment plants (WWTPs). FeNPs undergo dissolution, migration, and transformation in WWTPs, which can potentially affect the stable operation of anaerobic ammonia oxidation (anammox) systems and may be discharged with wastewater or biomass. To better understand the fate of FeNPs in anammox systems, exposure experiments were conducted using anammox granular sludges (AnGS) and FeNPs. Results demonstrated that FeNPs released Fe2+ upon contact with water, with a portion being bound to functional groups in extracellular polymeric substances (EPS) and the rest entering the bacteria to form highly absorbable substances. A significant amount of FeNPs was observed to cover the surface of AnGS or aggregate and deposit at the bottom of the reactor, eventually converting into Fe3O4 and stably existing within the anammox system. The findings of this study clarify the fate of FeNPs in anammox systems and provide important insights into the stable operation of anammox systems under FeNPs exposure.

[Development and Application of Ontology of Cancer Hallmarks].

Objective To develop a traceable cancer hallmark ontology with terminology including gene mutation,cancer hallmark,and cell line for knowledge integration,standardization,correlation,and discovery.Methods The Ontology Development 101 and the current ontology development methods were employed to determine the content coverage,structural layers,reusable terms,and new terms of the cancer hallmark ontology.Taking colorectal cancer as a study case,we extracted the knowledge related with colorectal cancer hallmarks using text mining and text classification technology from PubMed,and then formalized the extracted knowledge into the cancer hallmark ontology.Moreover,we made use of existing cancer hallmark evidence in Catalogue of Somatic Mutations in Cancer and further semantic retrieval to discover new knowledge.Results The established cancer hallmark ontology comprised 9910 classes and 6138 instances,which realized the semantic representation of 2310 article abstracts about colorectal cancer and 26 pieces of evidence about genes and their cancer hallmarks.Compared with the Catalogue of Somatic Mutations in Cancer,new evidence for more genes associated with colorectal cancer hallmarks was found based on cancer hallmark ontology.Conclusion This study is of great significance to the research on the cancer pathogenesis at the molecular level,the revealing of specific roles of genes and mutations in the occurrence of cancer,and the rapid knowledge discovery of cancer hallmarks.

Selective Photoaffinity Probe for Monitoring Farnesoid X Receptor Expression in Cultured Cells.

Farnesoid X receptor (FXR), a member of the nuclear receptor superfamily, is a vital ligand-activated transcriptional factor, which is highly expressed in the liver, intestine, and adrenal gland. However, FXR homeostasis is influenced by many factors, such as diet and circadian rhythm, and the expression of FXR differs in diverse organs. Currently, there is no method to monitor the FXR homeostasis in real time, which restricts us from further investigating the function of FXR under physiological and pathological conditions. In this project, classic FXR agonists were selected to be modified to targeting FXR. The photo-cross-linking diazirine group and alkynyl, a click reaction group, were incorporated to the ligands. Through biorthogonal reaction, fluorophore was linked to the ligands to realize the monitoring of FXR expression in cells.

Progress in hepatitis B virus-related acute-on-chronic liver failure treatment in China: A large, multicenter, retrospective cohort study using a propensity score matching analysis.

BACKGROUND: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) has a high short-term mortality. However, the treatment progression for HBV-ACLF in China in the past decade has not been well characterized. The present study aimed to determine whether the HBV-ACLF treatment has significantly improved during the past decade. METHODS: This study retrospectively compared short-term (28/56 days) survival rates of two different nationwide cohorts (cohort I: 2008-2011 and cohort II: 2012-2015). Eligible HBV-ACLF patients were enrolled retrospectively. Patients in the cohorts I and II were assigned either to the standard medical therapy (SMT) group (cohort I-SMT, cohort II-SMT) or artificial liver support system (ALSS) group (cohort I-ALSS, cohort II-ALSS). Propensity score matching analysis was conducted to eliminate baseline differences, and multivariate logistic regression analysis was used to explore the independent factors for 28-day survival. RESULTS: Short-term (28/56 days) survival rates were significantly higher in the ALSS group than those in the SMT group (P < 0.05) and were higher in the cohort II than those in the cohort I (P < 0.001). After propensity score matching, short-term (28/56 days) survival rates were higher in the cohort II than those in the cohort I for both SMT (60.7% vs. 53.0%, 50.0% vs. 39.8%, P < 0.05) and ALSS (66.1% vs. 56.5%, 53.0% vs. 44.4%, P < 0.05) treatments. The 28-day survival rate was higher in patients treated with nucleos(t)ide analogs than in patients without such treatments (P = 0.046). Multivariate logistic regression analysis revealed that ALSS (OR = 0.962, 95% CI: 0.951-0.973, P = 0.038), nucleos(t)ide analogs (OR = 0.927, 95% CI: 0.871-0.983, P = 0.046), old age (OR = 1.028, 95% CI: 1.015-1.041, P < 0.001), total bilirubin (OR = 1.002, 95% CI: 1.001-1.003, P = 0.004), INR (OR = 1.569, 95% CI: 1.044-2.358, P < 0.001), COSSH-ACLF grade (OR = 2.683, 95% CI: 1.792-4.017, P < 0.001), and albumin (OR = 0.952, 95% CI: 0.924-0.982, P = 0.002) were independent factors for 28-day mortality. CONCLUSIONS: The treatment for patients with HBV-ACLF has improved in the past decade.

CUDC-907 displays potent antitumor activity against human pancreatic adenocarcinoma in vitro and in vivo through inhibition of HDAC6 to downregulate c-Myc expression.

Pancreatic adenocarcinoma is a highly malignant cancer that often involves a deregulation of c-Myc. It has been shown that c-Myc plays a pivotal role in the regulation of a variety of physiological processes and is involved in early neoplastic development, resulting in poor progression. Hence, suppression of c-Myc overexpression is a potential strategy for pancreatic cancer therapy. CUDC-907 is a novel dual-acting inhibitor of phosphoinositide 3-kinase (PI3K) and histone deacetylase (HDAC). It has shown potential efficiency in patients with lymphoma, multiple myeloma, or thyroid cancer, as well as in solid tumors with c-Myc alterations, but the evidence is lacking for how CUDC-907 regulates c-Myc. In this study, we investigated the effect of CUDC-907 on human pancreatic cancer cells in vitro and in vivo. Our results showed that CUDC-907 potently inhibited the proliferation of 9 pancreatic cancer cell lines in vitro with IC50 values ranging from 6.7 to 54.5 nM. Furthermore, we revealed the antitumor mechanism of CUDC-907 in Aspc-1, PANC-1, and Capan-1 pancreatic cancer cells: it suppressed the HDAC6 subunit, thus downregulating c-Myc protein levels, which was a mode of action distinct from the existing mechanisms. Consistently, the extraordinary antitumor activity of CUDC-907 accompanied by downregulation of c-Myc and Ki67 expression in tumor tissue was observed in a human pancreatic cancer Aspc-1 xenograft nude mouse model in vivo. Our results suggest that CUDC-907 can be a valuable therapeutic option for treating pancreatic adenocarcinoma.

Borrelia miyamotoi Infections in Humans and Ticks, Northeastern China.

We conducted an investigation of Borrelia miyamotoi infections in humans and ticks in northeastern China. Of 984 patients reporting recent tick bites, 14 (1.4%) were found to be infected with B. miyamotoi by PCR and genomic sequencing. The 14 patients had nonspecific febrile manifestations, including fever, headache, anorexia, asthenia, and arthralgia. Rash, eschar, and regional lymphadenopathy were each observed in 1 patient. Four (28.6%) patients were hospitalized because of severe disease. B. miyamotoi was detected in 3.0% (19/627) of Ixodes persulcatus, 1 (2.8%) of 36 Haemaphysalis concinna, and none of 29 Dermacentor silvarum ticks. Phylogenetic analyses based on sequences of a nearly entire 16s rRNA gene, a partial flagellin gene, and the glycerophosphodiester phosphodiesterase gene revealed that B. miyamotoi identified in patients and ticks were clustered in the group of the Siberian type. These findings indicate that B. miyamotoi is endemic in northeastern China and its public health significance deserves further investigation.

Plasma exchange-centered artificial liver support system in hepatitis B virus-related acute-on-chronic liver failure: a nationwide prospective multicenter study in China.

BACKGROUND: Plasma exchange (PE)-centered artificial liver support system reduced the high mortality rate of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). But the data were diverse in different medical centers. The present prospective nationwide study was to evaluate the effects of PE on patients with HBV-ACLF at different stages. METHODS: From December 2009 to December 2011, we evaluated 250 patients at different stages of HBV-ACLF from 10 major medical centers in China. All the laboratory parameters were collected at admission, before and after PE. RESULTS: Among the 250 patients who underwent 661 rounds of PE, one-month survival rate was 61.6%; 141 (56.4%) showed improvement after PE. Variables such as age (P=0.000), levels of total bilirubin (TB, P=0.000), direct bilirubin (P=0.000), total triglycerides (P=0.000), low-density lipoprotein (P=0.022), Na+ (P=0.014), Cl- (P=0.038), creatinine (Cr, P=0.007), fibrinogen (P=0.000), prothrombin time (PT, P=0.000), white blood cell (P=0.000), platelet (P=0.003) and MELD (P=0.000) were significantly related to prognosis. Multivariate logistic regression analysis showed that age, disease stage, TB, Cr and PT levels were independent risk factors of mortality among HBV-ACLF patients. CONCLUSIONS: PE can improve the clinical outcome of patients with HBV-ACLF. Levels of TB, Cr and PT, age and disease stage help to predict prognosis.

Screening for Neuraminidase Inhibitory Activity in Traditional Chinese Medicines Used to Treat Influenza.

OBJECTIVE: To screen for influenza virus neuraminidase inhibition and to provide a reference for the clinical treatment of influenza using traditional Chinese medicines (TCM). In this study, 421 crude extracts (solubilized with petroleum ether, ethanol, ethyl acetate, and aqueous solvents) were obtained from 113 TCM. The medicine extracts were then reacted with oseltamivir, using 2'-(4-methylumbelliferyl)-α-D-N-acetylneuraminic acid (MUNANA) as the substrate, to determine influenza virus neuraminidase activity using a standard fluorimetric assay. It was found that Chinese medicine extracts from Pyrola calliantha, Cynanchum wilfordii, Balanophora involucrata and Paeonia delavayi significantly inhibited neuraminidase activity at a concentration of 40 µg/mL. Dose-dependent inhibitory assays also revealed significant inhibition. The IC50 range of the TCM extracts for influenza virus neuraminidase was approximately 12.66-34.85 µg/mL, respectively. Some Chinese medicines have clear anti-influenza viral effects that may play an important role in the treatment of influenza through the inhibition of viral neuraminidase. The results of this study demonstrated that plant medicines can serve as a useful source of neuraminidase (NA) inhibitors and further investigation into the pharmacologic activities of these extracts is warranted.

Hydraulic loss experiment of straight-through Tesla valve in forward and reverse directions.

Tesla valves are widely used in the field of fluid control. To study the hydraulic performance of straight-through Tesla valves in forward and reverse flow, 16 straight-through Tesla valves with diverse blade parameters were designed in this paper, and hydraulic loss tests were carried out in forward and reverse flow under different working conditions. The results show that the hydraulic loss increases with the increasing working flow rate in forward and reverse flow; at the identical flow rate, the reverse loss is higher than the forward loss. Both the hydraulic loss through the valve and the unidirectional conductivity of the valve increase with increasing blade length, pitch, and number of blades, but too long of a length results in weakened unidirectional conductivity. The hydraulic loss increases with the increase of blade angle, and the unidirectional conductivity decreases with the increase of blade angle. When the blades are arranged in perfect symmetry, the hydraulic loss through the valve is maximum, and the valve has the best unidirectional conductivity.

Using Quercetin to Construct Molecularly Imprinting Polymer in the Preparation and Enrichment of Flavonol and Flavonoid Compounds.

Flavonol and flavonoid compounds are important natural compounds with various biomedical activities. Therefore, it is of great significance to develop a strategy for the specific extraction of flavonol and flavonoid compounds. Quercetin is a well-studied flavonoid possessing many health benefits. This compound is a versatile antioxidant known to possess protective abilities against body tissue injury induced by pathological situations and various drug toxicities. Although quercetin is widely distributed in many plants, its content generally is not very high. Therefore, the specific extraction of quercetin as well as other flavonol and flavonoid compounds has profound significance. In this work, the quercetin molecularly imprinting polymer (QMIP) was successfully prepared, in which a typical flavonol quercetin was selected as the template molecule. QMIP was synthesized by performing the surface molecular imprinting technology on the surface of NH2-MIL-101(Fe). Our study results showed that QMIP exhibited quick binding kinetic behavior, a high adsorption capacity (57.04[Formula: see text]mg/g), and the specific recognition ability toward quercetin compared with structurally distinct compounds (selective [Formula: see text]). The specific adsorption ability of quercetin by QMIP was further explained using computation simulation that molecules with non-planar 3D conformations hardly entered the molecularly imprinted cavities on QMIP. Finally, QMIP was successfully used for the specific extraction of quercetin and five other flavonol and flavonoid compounds in the crude extracts from Sapium sebiferum. This study proposes a new strategy to synthesize the molecularly imprinted polymer based on a single template for enriching and loading a certain class of active ingredients with similar core structures from variable botanicals.

Motility behavior and physiological response mechanisms of aerobic denitrifier, Enterobacter cloacae strain HNR under high salt stress: Insights from individual cells to populations.

The motility behaviors at the individual-cell level and the collective physiological responsive behaviors of aerobic denitrifier, Enterobacter cloacae strain HNR under high salt stress were investigated. The results revealed that as salinity increased, electron transport activity and adenosine triphosphate content decreased from 15.75 µg O2/g/min and 593.51 mM/L to 3.27 µg O2/g/min and 5.34 mM/L, respectively, at 40 g/L, leading to a reduction in the rotation velocity and vibration amplitude of strain HNR. High salinity stress (40 g/L) down-regulated genes involved in ABC transporters (amino acids, sugars, metal ions, and inorganic ions) and activated the biofilm-related motility regulation mechanism in strain HNR, resulting in a further decrease in flagellar motility capacity and an increase in extracellular polymeric substances secretion (4.08 mg/g cell of PS and 40.03 mg/g cell of PN at 40 g/L). These responses facilitated biofilm formation and proved effective in countering elevated salt stress in strain HNR. Moreover, the genetic diversity associated with biofilm-related motility regulation in strain HNR enhanced the adaptability and stability of the strain HNR populations to salinity stress. This study enables a deeper understanding of the response mechanism of aerobic denitrifiers to high salt stress.

New insights into functional divergence and adaptive evolution of uncultured bacteria in anammox community by complete genome-centric analysis.

Anaerobic ammonium-oxidation (anammox) bacteria play a crucial role in global nitrogen cycling and wastewater nitrogen removal, but they share symbiotic relationships with various other microorganisms. Functional divergence and adaptive evolution of uncultured bacteria in anammox community remain underexplored. Although shotgun metagenomics based on short reads has been widely used in anammox research, metagenome-assembled genomes (MAGs) are often discontinuous and highly contaminated, which limits in-depth analyses of anammox communities. Here, for the first time, we performed Pacific Biosciences high-fidelity (HiFi) long-read sequencing on the anammox granule sludge sample from a lab-scale bioreactor, and obtained 30 accurate and complete metagenome-assembled genomes (cMAGs). These cMAGs were obtained by selecting high-quality circular contigs from initial assemblies of long reads generated by HiFi sequencing, eliminating the need for Illumina short reads, binning, and reassembly. One new anammox species affiliated with Candidatus Jettenia and three species affiliated with novel families were found in this anammox community. cMAG-centric analysis revealed functional divergence in general and nitrogen metabolism among the anammox community members, and they might adopt a cross-feeding strategy in organic matter, cofactors, and vitamins. Furthermore, we identified 63 mobile genetic elements (MGEs) and 50 putative horizontal gene transfer (HGT) events within these cMAGs. The results suggest that HGT events and MGEs related to phage and integration or excision, particularly transposons containing tnpA in anammox bacteria, might play important roles in the adaptive evolution of this anammox community. The cMAGs generated in the present study could be used to establish of a comprehensive database for anammox bacteria and associated microorganisms. These findings highlight the advantages of HiFi sequencing for the studies of complex mixed cultures and advance the understanding of anammox communities.

Identification and effective regulation of scarb1 gene involved in pigmentation change in autotetraploid Carassius auratus.

The autotetraploid Carassius auratus (4nRR, 4 n=200, RRRR) is derived from whole-genome duplication of Carassius auratus red var. (RCC, 2 n=100, RR). In the current study, we demonstrated that chromatophores and pigment changes directly caused the coloration and variation of 4nRR skin (red in RCC, brownish-yellow in 4nRR). To further explore the molecular mechanisms underlying coloration formation and variation in 4nRR, we performed transcriptome profiling and molecular functional verification in RCC and 4nRR. Results revealed that scarb1, associated with carotenoid metabolism, underwent significant down-regulation in 4nRR. Efficient editing of this candidate pigment gene provided clear evidence of its significant role in RCC coloration. Subsequently, we identified four divergent scarb1 homeologs in 4nRR: two original scarb1 homeologs from RCC and two duplicated ones. Notably, three of these homeologs possessed two highly conserved alleles, exhibiting biased and allele-specific expression in the skin. Remarkably, after precise editing of both the original and duplicated scarb1 homeologs and/or alleles, 4nRR individuals, whether singly or multiply mutated, displayed a transition from brownish-yellow skin to a cyan-gray phenotype. Concurrently, the proportional areas of the cyan-gray regions displayed a gene-dose correlation. These findings illustrate the subfunctionalization of duplicated scarb1, with all scarb1 genes synergistically and equally contributing to the pigmentation of 4nRR. This is the first report concerning the functional differentiation of duplicated homeologs in an autopolyploid fish, substantially enriching our understanding of coloration formation and change within this group of organisms.

[Meta-analysis on elemene injection combined with cisplatin chemotherapeutics in treatment of non-small cell lung cancer].

To research databases of Cochrane library, Web of Science, PubMed, FMJS, CBM, VIP, CNKI and Wanfang Data Konwledge Service Platform by computers as at July 5, 2012, which was supplemented with other search results. The findings were included into randomized controlled trials (RCTs) of elemene injection combined with cisplatin chemotherapeuties in treating small cell lung cancer (NSCLC). Data was separately collected by two researchers for literature quality evaluation, and a Meta analysis was made with RevMan 5. 2 software, in order to assess the efficacy and safety of elemene injection combined with cisplatin chemotherapeutics in treating NSCLC. Totally 11 RCTs or 844 cases were included. Meta analysis results suggested that compared with cisplatin chemotherapy alone, the combination of elemene injection and cisplatin chemotherapeutics showed a higher clinical benefit rate ( OR = 2. 03, 95% CI:1.43-2. 88, P <0. 000 1) and a better quality of life (OR = 3.23, 95% CI:2. 20-4. 74, P <0. 000 01). Besides,the combination could also reduce leucopenia (OR =0. 50, 95% CI:0. 33-0. 76, P <0. 001) , and thrombocytopenia (OR =0. 38, 95% CI:0. 16-0. 85, P <0. 02), increase CD4 (MD = 3.32, 95% C1:2. 94-3.70, P <0. 000 01), and CD4/CD8 (MD = 0. 36, 95% CI:0. 28-0. 44, P < 0. 000 01) , and relieve gastrointestinal reactions such as nausea and vomiting (OR = 0. 37, 95% CI: 0. 19-0. 71, P = 0. 003). The analysis indicates that elemene can enhance the chemotherapeutic effect on NSCLC, improve the quality of life, and reduce adverse effect of platinum-contained chemotherapeutics, thereby being worth promoting in clinic.

[Research progress on biomass ash carbon capture and storage]. / ç”Ÿç‰©è´¨ç°çš„ç¢³æ•é›†ä¸Žå°å­˜ç ”ç©¶è¿›å±•.

Carbon capture and storage (CCS) technology is an important way to slow down the continuous increase in atmospheric CO2 concentration and to achieve the dual carbon target. Carbon capture and storage through biomass ash is a secure, permanent, and environment friendly way. To better understand the characteristics of biomass ash carbon capture and storage, we summarized progresses on biomass ash carbon capture and storage, clarified the mechanisms of biomass ash carbon sequestration, analyzed the influencing factors, and explored its applications in various domains. The capacity of CCS by biomass ash mainly derived from alkaline earth metal oxides of CaO and MgO. The actual carbon sequestration efficiency is affected by factors such as biomass source, chemical composition, temperature, humidity, pressure, and CO2 concentration. However, the underlying mechanism is unclear. The CCS capacity of biomass ash significantly impacts its potential applications in building materials reuse, soil quality improvement, and adsorbents carbon capture and storage absorbent preparation. Long-term research is critically needed. For future studies, we should strengthen the research on the carbonization efficiency of biomass ash from multiple sources, establish a database related to the impact of biomass ash carbonization, build a methodological system to promote scientific management of biomass ash, develop biomass ash carbon capture and storage technologies, and quantitatively assess its role in carbon sequestration.

Basal cell carcinoma of the scrotum: clinicopathologic analysis of 10 cases.

BACKGROUND: Basal cell carcinoma (BCC) located on the scrotum is rare. OBJECTIVE: To analyze clinical and pathologic features, discuss therapeutic strategies, and identify prognostic factors of scrotal BCC in Chinese patients. MATERIALS AND METHODS: Between 2000 and 2010, 10 patients with scrotal BCC were diagnosed and treated at our institution. A review was performed using the clinical records and dermatopathologic slides of these patients. RESULTS: The median patient age was 70. Skin lesions presented as red nodules and brownish plaques. All patients were treated using wide excision without adjuvant therapy. After an average follow-up of 47 months, eight patients were in good health without any relapse. One patient developed left inguinal lymph node metastasis at 21 months that was successfully treated using bilateral inguinal lymphadenectomy. One patient developed bilateral pulmonary metastasis at 48 months and was palliatively treated with chemotherapy. The clinical and histopathologic risk factors predisposing to metastasis were large primary neoplasms; a long period of misdiagnosis; and infiltrating, morpheaform, spiky, irregular outline pathologic patterns. CONCLUSIONS: BCC of the scrotum is rare. It can metastasize after a long period of initial therapy. Long-term surveillance including a complete metastatic examination is recommended for these patients.