Fecal Microbiota Transplantation Improves Clinical Symptoms of Fibromyalgia: An open-label, Randomized, Nonplacebo-Controlled Study.

Fibromyalgia (FM) is a complex and poorly understood disorder characterized by chronic and widespread musculoskeletal pain, of which the etiology remains unknown. Now, the disorder of the gut microbiome is considered as one of the main causes of FM. This study was aimed to investigate the potential benefits of fecal microbiota transplantation (FMT) in patients with FM. A total of 45 patients completed this open-label randomized, nonplacebo-controlled clinical study. The Numerical Rating Scale (NRS) scores in the FMT group were slightly lower than the control group at 1 month (P> 0.05), and they decreased significantly at 2, 3, 6, and 12 months after treatment (P < 0.001). Besides, compared with the control group, the Widespread Pain Index (WPI), Symptom Severity (SS), Hospital Anxiety and Depression Scale (HADS) and Pittsburgh Sleep Quality Index (PSQI) scores were significantly lower in the FMT group at different time points (P < 0.001). After 6 months of treatment, there was a significant increase in serotonin (5-HT) and gamma-aminobutyric acid (GABA) levels (P < 0.001), while glutamate levels significantly decreased in the FMT group (P < 0.001). The total effective rate was higher in the FMT group (90.9%) compared to the control group (56.5%) after 6 months of treatment (P < 0.05). FMT can effectively improve the clinical symptoms of FM. With the close relations between the changes of neurotransmitters and FM, certain neurotransmitters may serve as a diagnostic marker or potential target for FM patients. PERSPECTIVE: Fecal microbiota transplantation (FMT) is a novel therapy that aims to restore the gut microbial balance and modulate the gut-brain axis. It is valuable to further explore the therapeutic effect of FMT on FM. Furthermore, certain neurotransmitters may become a diagnostic marker or a new therapeutic target for FM patients.

Surface and interface engineering of BiOCl nanomaterials and their photocatalytic applications.

BiOCl materials have received much attention because of their unique optical and electrical properties. Still, their unsatisfactory catalytic performance has been troubling researchers, limiting the application of BiOCl-based photocatalysts. Therefore, many researchers have studied the adjustment of BiOCl-based materials to enhance photocatalytic efficiency. This review focuses on surface and interface engineering strategies for boosting the photocatalytic performance of BiOCl-based nanomaterials, including forming oxygen vacancy defects, constructing metal/BiOCl, and the fabrication of semiconductor/BiOCl nanocomposites. The photocatalytic applications of the above composites are also concluded in photodegradation of aqueous pollutants, photocatalytic NO removal, photo-induced H2 production, and CO2 reduction. Special emphasis has been given to the modification methods of BiOCl and photocatalytic mechanisms to provide a more detailed understanding for researchers in the fields of energy conversion and materials sciences.

Bi/Mn-Doped BiOCl Nanosheets Self-Assembled Microspheres toward Optimized Photocatalytic Performance.

Doping engineering of metallic elements is of significant importance in photocatalysis, especially in the transition element range where metals possess empty 'd' orbitals that readily absorb electrons and increase carrier concentration. The doping of Mn ions produces dipole interactions that change the local structure of BiOCl, thus increasing the specific surface area of BiOCl and the number of mesoporous distributions, and providing a broader platform and richer surface active sites for catalytic reactions. The combination of Mn doping and metal Bi reduces the forbidden bandwidth of BiOCl, thereby increasing the absorption in the light region and strengthening the photocatalytic ability of BiOCl. The degradation of norfloxacin by Bi/Mn-doped BiOCl can reach 86.5% within 10 min. The synergistic effect of Mn doping and Bi metal can change the internal energy level and increase light absorption simultaneously. The photocatalytic system created by such a dual-technology combination has promising applications in environmental remediation.

Colitis ameliorates cholestatic liver disease via suppression of bile acid synthesis.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by chronic inflammation and progressive fibrosis of the biliary tree. The majority of PSC patients suffer from concomitant inflammatory bowel disease (IBD), which has been suggested to promote disease development and progression. However, the molecular mechanisms by which intestinal inflammation may aggravate cholestatic liver disease remain incompletely understood. Here, we employ an IBD-PSC mouse model to investigate the impact of colitis on bile acid metabolism and cholestatic liver injury. Unexpectedly, intestinal inflammation and barrier impairment improve acute cholestatic liver injury and result in reduced liver fibrosis in a chronic colitis model. This phenotype is independent of colitis-induced alterations of microbial bile acid metabolism but mediated via hepatocellular NF-κB activation by lipopolysaccharide (LPS), which suppresses bile acid metabolism in-vitro and in-vivo. This study identifies a colitis-triggered protective circuit suppressing cholestatic liver disease and encourages multi-organ treatment strategies for PSC.

Construction of 2D/2D Mesoporous WO3/CeO2 Laminated Heterojunctions for Optimized Photocatalytic Performance.

Photocatalytic elimination of antibiotics from the environment and drinking water is of great significance for human health. However, the efficiency of photoremoval of antibiotics such as tetracycline is severely limited by the prompt recombination of electron holes and slow charge migration efficacy. Fabrication of low-dimensional heterojunction composites is an efficient method for shortening charge carrier migration distance and enhancing charge transfer efficiency. Herein, 2D/2D mesoporous WO3/CeO2 laminated Z-scheme heterojunctions were successfully prepared using a two-step hydrothermal process. The mesoporous structure of the composites was proved by nitrogen sorption isotherms, in which sorption-desorption hysteresis was observed. The intimate contact and charge transfer mechanism between WO3 nanoplates and CeO2 nanosheets was investigated using high-resolution transmission electron microscopy and X-ray photoelectron spectroscopy measurements, respectively. Photocatalytic tetracycline degradation efficiency was noticeably promoted by the formation of 2D/2D laminated heterojunctions. The improved photocatalytic activity could be attributed to the formation of Z-scheme laminated heterostructure and 2D morphology favoring spatial charge separation, confirmed by various characterizations. The optimized 5WO3/CeO2 (5 wt.% WO3) composites can degrade more than 99% of tetracycline in 80 min, achieving a peak TC photodegradation efficiency of 0.0482 min-1, which is approximately 3.4 times that of pristine CeO2. A Z-scheme mechanism is proposed for photocatalytic tetracycline by from WO3/CeO2 Z-scheme laminated heterojunctions based on the experimental results.

High-Crystallinity BiOCl Nanosheets as Efficient Photocatalysts for Norfloxacin Antibiotic Degradation.

Semiconductor photocatalysts are essential materials in the field of environmental remediation. Various photocatalysts have been developed to solve the contamination problem of norfloxacin in water pollution. Among them, a crucial ternary photocatalyst, BiOCl, has attracted extensive attention due to its unique layered structure. In this work, high-crystallinity BiOCl nanosheets were prepared using a one-step hydrothermal method. The obtained BiOCl nanosheets showed good photocatalytic degradation performance, and the degradation rate of highly toxic norfloxacin using BiOCl reached 84% within 180 min. The internal structure and surface chemical state of BiOCl were analyzed using scanning electron microscopy (SEM), transmission electron microscopy (TEM), Raman, Fourier transform infrared spectroscopy (FTIR), UV-visible diffuse reflectance (UV-vis), Brunauer-Emmett-Teller (BET), X-ray photoelectron spectra (XPS), and photoelectric techniques. The higher crystallinity of BiOCl closely aligned molecules with each other, which improved the separation efficiency of photogenerated charges and showed high degradation efficiency for norfloxacin antibiotics. Furthermore, the obtained BiOCl nanosheets possess decent photocatalytic stability and recyclability.

The Effects of Ginkgo biloba Extract on Autophagy in Human Macrophages Stimulated by Cigarette Smoke Extract.

OBJECTIVE: To investigate the effects of Ginkgo biloba extract (GBE) on autophagy in human macrophages stimulated by cigarette smoke extract (CSE). METHODS: The human monocyte cell line U937 was cultured in vitro, and phorbol ester (PMA) was added to the cell culture medium to induce differentiation into human macrophages. CSE was prepared by traditional methods for experiments. The cells were divided into four groups: the blank group, the CSE model group, the GBE + CSE group, and the rapamycin + CSE group. Immunofluorescence was used to identify human macrophages, transmission electron microscopy was used to observe the ultrastructure of human macrophages in each group, ELISA was used to measure the amount of IL-6 and IL-10 in the supernatant from each group of cells, the mRNA levels of p62, ATG5, ATG7, and Rab7 were measured by real-time qPCR, and the protein expression levels of p62, ATG5, ATG7, and Rab7 were measured by Western blotting. RESULTS: U937 cells were successfully differentiated into human macrophages after induction with PMA. The CSE model group had many more autophagosomes than the blank group. Compared with the CSE model group, the GBE + CSE group and the rapamycin + CSE group had significantly more autophagolysosomal. Compared with the other groups, the CSE model group had a higher level of IL-6 but a lower level of IL-10 in the supernatant (p < 0.05). Compared with the blank group, the mRNA and protein expression levels of p62 in the CSE model group were significantly decreased, while the mRNA and protein expression levels of ATG5 and ATG7 were significantly increased in the CSE model group (p < 0.05). No difference was found in the mRNA and protein expression levels of Rab7 between the blank group and the CSE model group. Compared with the CSE model group, the IL-6 level in the GBE + CSE group and the rapamycin + CSE group cell culture supernatant decreased significantly, p62 mRNA and protein expression significantly decreased, while ATG5, ATG7, and Rab7 mRNA and protein expression levels were significantly increased (p < 0.05). Moreover, increased LC3-II/LC3-I ratio were also found in the GBE + CSE group and the rapamycin + CSE group compared with the CSE model group. CONCLUSIONS: GBE could promote the fusion of autophagosomes and lysosomes in human macrophages, enhance the autophagy function of human macrophages, and reduce the damaging effect of CSE on the autophagy function of macrophages.

Long-term hypercaloric diet exacerbates metabolic liver disease in PNPLA3 I148M animals.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is a major health burden associated with the metabolic syndrome leading to liver fibrosis, cirrhosis and ultimately liver cancer. In humans, the PNPLA3 I148M polymorphism of the phospholipase patatin-like phospholipid domain containing protein 3 (PNPLA3) has a well-documented impact on metabolic liver disease. In this study, we used a mouse model mimicking the human PNPLA3 I148M polymorphism in a long-term high fat diet (HFD) experiment to better define its role for NAFLD progression. METHODS: Male mice bearing wild-type Pnpla3 (Pnpla3WT ), or the human polymorphism PNPLA3 I148M (Pnpla3148M/M ) were subjected to HFD feeding for 24 and 52 weeks. Further analysis concerning basic phenotype, inflammation, proliferation and cell death, fibrosis and microbiota were performed in each time point. RESULTS: After 52 weeks HFD Pnpla3148M/M animals had more liver fibrosis, enhanced numbers of inflammatory cells as well as increased Kupffer cell activity. Increased hepatocyte cell turnover and ductular proliferation were evident in HFD Pnpla3148M/M livers. Microbiome diversity was decreased after HFD feeding, changes were influenced by HFD feeding (36%) and the PNPLA3 I148M genotype (12%). Pnpla3148M/M mice had more faecal bile acids. RNA-sequencing of liver tissue defined an HFD-associated signature, and a Pnpla3148M/M specific pattern, which suggests Kupffer cell and monocytes-derived macrophages as significant drivers of liver disease progression in Pnpla3148M/M animals. CONCLUSION: With long-term HFD feeding, mice with the PNPLA3 I148M genotype show exacerbated NAFLD. This finding is linked to PNPLA3 I148M-specific changes in microbiota composition and liver gene expression showing a stronger inflammatory response leading to enhanced liver fibrosis progression.

An in vivo evaluation of clear aligners for optimal orthodontic force and movement to determine high-efficacy and periodontal-friendly aligner staging.

Objectives: To investigate the effect of aligner displacement on tooth movement and periodontal health to improve the efficiency of aligner treatment and explore the mechanism in vivo. Methods: A two-tooth site was established by a finite element (FE) model to virtually evaluate aligner staging. A randomized controlled experiment was conducted when the tooth sites in beagles were treated with fixed or aligner appliances with different movement and force, and tooth movement and internal structure were recorded during the alignment. After sacrificing five dogs, bone-periodontal ligament (PDL)-tooth specimens were removed and processed to conduct uniaxial compression and tensile tests as well as micro-CT imaging and histological analysis. Results: Three displacements of 0.25, 0.35 and 0.45 mm were obtained from FE analysis and applied in beagles. In general, aligners had poorer performance on movement compared to fixed systems in vivo, but the aligner with a staging of 0.35 mm had the highest accuracy (67.46%) (P < 0.01). Loaded with severe force, fixed sites exhibited tissue damage due to excess force and rapid movement, while aligners showed better safety. The PDL under a 0.35-mm aligner treatment had the highest elastic modulus in the biomechanical test (551.4275 and 1298.305 kPa) (P < 0.05). Conclusions: Compared to fixed appliances, aligners achieve slightly slower movement but better periodontal condition. Aligners with an interval of 0.35 mm have the highest accuracy and best PDL biomechanical and biological capacities, achieving the most effective and safest movement. Even with complexity of oral cavity and lack of evaluation of other factors, these results provide insight into faster displacement as a method to improve the efficacy of aligners.

Recent Advances in Black TiO2 Nanomaterials for Solar Energy Conversion.

Titanium dioxide (TiO2) nanomaterials have been widely used in photocatalytic energy conversion and environmental remediation due to their advantages of low cost, chemical stability, and relatively high photo-activity. However, applications of TiO2 have been restricted in the ultraviolet range because of the wide band gap. Broadening the light absorption of TiO2 nanomaterials is an efficient way to improve the photocatalytic activity. Thus, black TiO2 with extended light response range in the visible light and even near infrared light has been extensively exploited as efficient photocatalysts in the last decade. This review represents an attempt to conclude the recent developments in black TiO2 nanomaterials synthesized by modified treatment, which presented different structure, morphological features, reduced band gap, and enhanced solar energy harvesting efficiency. Special emphasis has been given to the newly developed synthetic methods, porous black TiO2, and the approaches for further improving the photocatalytic activity of black TiO2. Various black TiO2, doped black TiO2, metal-loaded black TiO2 and black TiO2 heterojunction photocatalysts, and their photocatalytic applications and mechanisms in the field of energy and environment are summarized in this review, to provide useful insights and new ideas in the related field.

[Research progress on the relationship between gut-liver axis disorder and sepsis].

Sepsis is a life-threatening organ dysfunction caused by an uncontrolled host response to infection. The mechanism of sepsis is extremely complicated and the mortality is still high. Persistent researches provide an important way to break through the "bottleneck" of clinical diagnosis and treatment of sepsis. In recent years, more and more studies have shown that gut-liver axis disorders, especially those caused by intestinal dysbiosis, intestinal barrier dysfunction, abnormal liver immune function, and bile acid metabolism disorders, play an important role in the occurrence and development of sepsis. This review describes the research progress of gut-liver axis disorders in the pathogenesis of sepsis for providing new ideas for clinical treatment.

Intravenous Lidocaine Significantly Reduces the Propofol Dose in Elderly Patients Undergoing Gastroscopy: A Randomized Controlled Trial.

Objective: Propofol-based sedation has been widely used for gastroscopy, but the risk of respiratory suppression in elderly patients should not be overlooked. Intravenous (IV) lidocaine during surgery can reduce the demand for propofol and the incidence of cardiopulmonary complications. We examined whether IV lidocaine reduces the dose of propofol and the occurrence of adverse events during gastroscopy in elderly patients. Methods: We conducted a prospective, single-center, double-blind randomized controlled trial in elderly patients aged ≥65 years with ASA I-II. Subjects were randomly assigned to the lidocaine group (Group L, n=70), who received IV 1.5 mg kg-1 lidocaine followed by a continuous infusion of 4 mg kg-1 h-1 lidocaine, or the normal saline group (Group N, n=70), who received an equal volume of saline in the same way. Results: IV lidocaine reduced the total and maintenance propofol dose in Group L (p<0.001), with no significant effect on the induction dose. The incidence of intraoperative hypoxia (p=0.035), emergency airway management events (p=0.005), duration of gastroscopy (p<0.05), consciousness recovery time (p<0.001), and postoperative pain (p=0.009) were all reduced in Group L. Patient (p=0.025) and gastroscopist (p=0.031) satisfaction was higher in Group L. Intraoperative hemodynamic parameters, the respiratory rate, the incidence of sedation-related events and anesthesiologist satisfaction were similar between the two groups. Conclusion: IV lidocaine can significantly reduce the amount of propofol, the incidence of hypoxia and postoperative pain during gastroscopy in elderly patients, with a higher patient and gastroscopist satisfaction.

Surface engineering of hematite nanorods photoanode towards optimized photoelectrochemical water splitting.

Rapid charge recombination in hematite (Fe2O3) during photoelectrochemical water splitting is a major obstacle to achieving high-efficiency photoelectrodes. Surface defect engineering is considered as a viable strategy for enhancing photoelectrochemical activity of oxide photoanodes. Herein, a one-dimensional (1D) defective γ-Fe2O3 nanorods (DFNRs) photoanode is prepared using solvothermal and high-temperature hydrogenation strategies. The as-prepared DFNRs possess superior visible-light absorption capacity and exhibit excellent photoelectrochemical performance (0.98 mA cm-2), with approximately three-fold higher photocurrent density than that of pristine Fe2O3 (FNRs, 0.32 mA cm-2). The enhanced activity of the DFNRs results from the moderate formation of oxygen vacancy defects, which promotes spatial charge separation and transfer at the DFNRs/electrolyte interface, as well as the 1D nanorod structure, which favors rapid charge transfer. The surface of γ-Fe2O3 with hydroxyl (OH) groups provides sufficient surface-active sites. This result suggests that surface-oxygen deficiency of γ-Fe2O3 can not only expand the light absorption range but also facilitating photo-generated charge carriers separation. This surface engineering strategy provides an alternative method for preparing stable and highly active metal oxide photoanodes for photoelectrochemical water splitting.

16-membered ring macrolides and erythromycin induce ermB expression by different mechanisms.

BACKGROUND: Ribosome stalling on ermBL at the tenth codon (Asp) and mRNA stabilization are believed to be mechanisms by which erythromycin (Ery) induces ermB expression. Expression of ermB is also induced by 16-membered ring macrolides (tylosin, josamycin and spiramycin), but the mechanism underlying this induction is unknown. METHODS: We introduced premature termination codons, alanine-scanning mutagenesis and amino acid mutations in ermBL and ermBL2. RESULTS: In this paper, we demonstrated that 16-membered ring macrolides can induce ermB expression but not ermC expression. The truncated mutants of the ermB-coding sequence indicate that the regulatory regions of ermB whose expression is induced by Ery and 16-membered ring macrolides are different. We proved that translation of the N-terminal region of ermBL is key for the induction of ermB expression by Ery, spiramycin (Spi) and tylosin (Tyl). We also demonstrated that ermBL2 is critical for the induction of ermB expression by erythromycin but not by 16-membered ring macrolides. CONCLUSIONS: The translation of ermBL and the RNA sequence of the C-terminus of ermBL are critical for the induction of ermB expression by Spi and Tyl.

Clinical Effects and Safety of the Use of Methylene Blue for the Treatment of Lumbar Facet Joint Syndrome.

BACKGROUND: Lumbar facet joint syndrome (LFJS) has been suggested to be a main source of low back pain. Methylene blue (MB), an inhibitor of nitric oxide synthesis with potential analgesic and anti-inflammatory properties, has been widely applied for a variety of pain-related diseases. However, no studies have been conducted on the treatment of LFJS patients using MB. OBJECTIVES: The purpose of this study was to evaluate the therapeutic effects of intra-articular injection of MB on LFJS patients. STUDY DESIGN: A prospective, randomized, controlled clinical trial. SETTING: Department of pain, Shanghai East Hospital. METHODS: A total of 120 eligible patients with LFJS were randomly divided into an MB group and a control group. Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire-9 (PHQ-9) were used to evaluate the pre-operation and post-operation states of the patients, and adverse events were recorded. The patients participating in this study were followed up for a period of 6 months. RESULTS: A total of 104 patients were followed up for the entire 6 months period. The control group included 51 patients, and the MB group included 53 patients. In both groups, the NRS scores, ODI scores, PHQ-9 scores, and PSQI scores decreased at different time points after treatment, compared to baseline. Moreover, the NRS scores were significantly lower than that of the control group at 3 months and 6 months after operation (P < 0.05). The ODI, PSQI, and PHQ-9 scores of the MB group were also respective significantly lower than that of the control group at 3 months and 6 months after operation (P < 0.05). As for the clinical efficacy, the total effective treatment rate of the MB group was significantly higher than that of the control group at 6 months after the procedure (P < 0.05). On the first day after operation, the incidence of hyperglycemia in patients with diabetes in the MB group was significantly lower than that of the control group (P < 0.05). LIMITATIONS: Firstly, the patients enrolled were recruited from a single center, and the sample size was small. Secondly, the patients were only followed-up for a period of 6 months after treatment. Thirdly, double blinding was not used in the design of this research study. CONCLUSION: Ultrasound-guided intra-articular MB injection is a safe and effective therapy for patients with LFJS. Intra-articular injection with MB can significantly reduce pain intensity, improve patient lumbar function, pain-related depression and sleep quality, increase total effective rate with no severe adverse side effects.

Acupoint Catgut Embedding as Adjunctive Therapy for Patients With Gallstones.

AIMS OF THIS STUDY: A randomized clinical trial was undertaken to investigate the efficacy of acupoint catgut embedding (ACE) as adjunctive therapy to tauroursodeoxycholic acid (TUDCA) therapy on gallbladder emptying and clinical symptoms in patients with gallstone disease. MATERIALS AND METHODS: Between August 2018 and January 2019, 70 patients with gallstones in our hospital were enrolled in this prospective clinical trial. All the patients were randomly divided into the ACE group (ACE+TUDCA treatment for 8 wk) and the Sham group (Sham ACE+TUDCA treatment for 8 wk). In the ACE group, all the patients were nightly given ACE every 2 weeks, and in 2 groups, every patient took TUDCA 500 mg at bedtime. The parameters about gallbladder emptying were detected by ultrasound before and after the treatment, and the clinical symptom scores were recorded at the same time points. RESULTS: A total of 63 patients with gallstone disease were included in our study, with 33 patients in the ACE group and 30 patients in the Sham group. In the ACE group, the empty volume (EV) and gallbladder ejection fraction (GBEF) were improved after treatment (P<0.05). Almost every symptom score (except symptom 7, P=0.15) and total score were decreased (P<0.05). In the Sham group, the symptom 1, 2, 4, 5 scores, and total score were significantly decreased (P<0.05). Moreover, the residual volume in the ACE group was significantly lower than in the Sham group (P=0.008). The EV and GBEF in the ACE group were higher than that in the Sham group (P<0.05). The score of symptom 6 in the ACE group was lower than that in the Sham group (P=0.008). CONCLUSION: ACE therapy could more effectively improve the gallbladder emptying with a shorter treatment course. Therefore, ACE+TUDCA therapy might be a time-saving treatment for gallstones.

Gut microbiota depletion exacerbates cholestatic liver injury via loss of FXR signalling.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology for which there are no approved therapeutic options. Patients with PSC display changes in gut microbiota and in bile acid (BA) composition; however, the contribution of these alterations to disease pathogenesis remains controversial. Here we identify a role for microbiota-dependent changes in BA synthesis that modulates PSC pathophysiology. In a genetic mouse model of PSC, we show that loss of microbiota-mediated negative feedback control of BA synthesis results in increased hepatic BA concentrations, disruption of bile duct barrier function and, consequently, fatal liver injury. We further show that these changes are dependent on decreased BA signalling to the farnesoid X receptor, which modulates the activity of the rate-limiting enzyme in BA synthesis, CYP7A1. Moreover, patients with advanced stages of PSC show suppressed BA synthesis as measured by serum C4 levels, which is associated with poor disease prognosis. Our preclinical data highlight the microbiota-dependent dynamics of BA metabolism in cholestatic liver disease, which could be important for future therapies targeting BA and gut microbiome interactions, and identify C4 as a potential biomarker to functionally stratify patients with PSC and predict disease outcomes.

Three-Dimensional Finite Element Analysis of L4-5 Degenerative Lumbar Disc Traction under Different Pushing Heights.

Objective: To study and analyze the changes of intervertebral foramen height and area of the degenerative L4-5 intervertebral disc under different pushing heights by the finite element method. Methods: CT and MRI images of T12-S1 segments were obtained from a healthy volunteer who met the inclusion criteria. A DR machine was used to capture images of the lumbar lateral section before and after simultaneous pushing of the L4 and L5 spinous processes by manipulation called Daogaijinbei, and the measurement showed that the displacement changes of L4 and L5 were both approximately 10 cm, so the pushing height was set at 0-10 cm. A three-dimensional finite element model of the entire normal lumbar spine was established using Mimics 16.0, Geomagic Studio 2014, Hypermesh 13.0, MSC.Patran 2012, and so on. The disc height and nucleus area of the lumbar disc of the normal entire lumbar disc model were adjusted to establish models of the L4-5 disc with mild, moderate, and severe degeneration. Changes of disc height and area of the L4-5 degenerative intervertebral disc under different pushing heights were calculated. Results: The size of the L4-5 intervertebral foramen was analyzed from the height and area of the intervertebral foramen, and the results showed the following: (1) as for the normal lumbar disc and a lumbar of the L4-5 disc with mild and moderate degeneration, the height of the L4-5 intervertebral foramen and its area both increased during pushing between 0 and 8 cm. After the pushing height reached 8 cm, the height and area of the L4-5 intervertebral foramen gradually became stable; (2) as for the L4-5 disc with severe degeneration, during the process of pushing, the height and area of the L4-5 intervertebral foramen increased slightly, but this change was not obvious. Conclusions: After the spinal manipulation, the sizes of the L4-5 intervertebral foramen of the L4-5 disc with mild and moderate degeneration were significantly larger than those before pushing; in contrast, the size of L4-5 intervertebral foramen of the L4-5 disc with severe lumbar degeneration was not significantly changed.

Translational Attenuation Mechanism of ErmB Induction by Erythromycin Is Dependent on Two Leader Peptides.

Ribosome stalling on ermBL at the tenth codon (Asp) is believed to be a major mechanism of ermB induction by erythromycin (Ery). In this study, we demonstrated that the mechanism of ermB induction by Ery depends not only on ermBL expression but also on previously unreported ermBL2 expression. Introducing premature termination codons in ermBL, we proved that translation of the N-terminal region of ermBL is the key component for ermB induced by Ery, whereas translation of the C-terminal region of ermBL did not affect Ery-induced ermB. Mutation of the tenth codon (Asp10) of ermBL with other amino acids showed that the degree of induction in vivo was not completely consistent with the data from the in vitro toe printing assay. Alanine-scanning mutagenesis of ermBL demonstrated that both N-terminal residues (R7-K11) and the latter part of ermBL (K20-K27) are critical for Ery induction of ermB. The frameshifting reporter plasmid showed that a new leader peptide, ermBL2, exists in the ermB regulatory region. Further, introducing premature termination mutation and alanine-scanning mutagenesis of ermBL2 demonstrated that the N-terminus of ermBL2 is essential for induction by Ery. Therefore, the detailed function of ermBL2 requires further study.

A MicroRNA-Based Network Provides Potential Predictive Signatures and Reveals the Crucial Role of PI3K/AKT Signaling for Hepatic Lineage Maturation.

BACKGROUND: Functions of miRNAs involved in tumorigenesis are well reported, yet, their roles in normal cell lineage commitment remain ambiguous. Here, we investigated a specific "transcription factor (TF)-miRNA-Target" regulatory network during the lineage maturation of biliary tree stem cells (BTSCs) into adult hepatocytes (hAHeps). METHOD: Bioinformatic analysis was conducted based on our RNA-seq and microRNA-seq datasets with four human hepatic-lineage cell lines, including hBTSCs, hepatic stem cells (hHpSCs), hepatoblasts (hHBs), and hAHeps. Short time-series expression miner (STEM) analysis was performed to reveal the time-dependent dynamically changed miRNAs and mRNAs. GO and KEGG analyses were applied to reveal the potential function of key miRNAs and mRNAs. Then, the miRDB, miRTarBase, TargetScan, miRWalk, and DIANA-microT-CDS databases were adopted to predict the potential targets of miRNAs while the TransmiR v2.0 database was used to obtain the experimentally supported TFs that regulate miRNAs. The TCGA, Kaplan-Meier Plotter, and human protein atlas (HPA) databases and more than 10 sequencing data, including bulk RNA-seq, microRNA-seq, and scRNA-seq data related to hepatic development or lineage reprogramming, were obtained from both our or other published studies for validation. RESULTS: STEM analysis showed that during the maturation from hBTSCs to hAHeps, 52 miRNAs were downwardly expressed and 928 mRNA were upwardly expressed. Enrichment analyses revealed that those 52 miRNAs acted as pluripotency regulators for stem cells and participated in various novel signaling pathways, including PI3K/AKT, MAPK, and etc., while 928 mRNAs played important roles in liver-functional metabolism. With an extensive sorting of those key miRNAs and mRNAs based on the target prediction results, 23 genes were obtained which not only functioned as the targets of 17 miRNAs but were considered critical for the hepatic lineage commitment. A "TF-miRNA-Target" regulatory network for hepatic lineage commitment was therefore established and had been well validated by various datasets. The network revealed that the PI3K/AKT pathway was gradually suppressed during the hepatic commitment. CONCLUSION: A total of 17 miRNAs act as suppressors during hepatic maturation mainly by regulating 23 targets and modulating the PI3K/AKT signaling pathway. The regulatory network uncovers possible signatures and guidelines enabling us to identify or obtain the functional hepatocytes for future study.