MicroRNA-130b Suppresses Malignant Behaviours and Inhibits the Activation of the PI3K/Akt Signaling Pathway by Targeting MET in Pancreatic Cancer.

There has been interested in the microRNAs' roles in pancreatic cancer (PC) cell biology, particularly in regulating pathways related to tumorigenesis. The study aimed to explore the hub miRNAs in PC and underlying mechanisms by bioinformatics and fundamental experiments. RNA datasets collected from the Gene Expression Omnibus were analysed to find out differentially expressed RNAs (DERNAs). The miRNA-mRNA and protein-protein interaction (PPI) networks were built. The clinicopathological features and expressions of hub miRNAs and hub mRNAs were explored. Dual-luciferase reporter gene assay was performed to assess the interaction between microRNA and target gene. RT-qPCR and western blot were employed to explore RNA expression. The roles of RNA were detected by CCK-8 test, wound healing, transwell, and flow cytometry experiment. We verified 40 DEmiRNAs and 1613 DEmRNAs, then detected a total of 69 final functional mRNAs (FmRNAs) and 23 DEmiRNAs. In the miRNA-mRNA networks, microRNA-130b (miR-130b) was the hub RNA with highest degrees. Clinical analysis revealed that miR-130b was considerably lower expressed in cancerous tissues than in healthy ones, and patients with higher-expressed miR-130b had a better prognosis. Mechanically, miR-130b directly targeted MET in PC cells. Cell functional experiments verified that miR-130b suppressed cell proliferation, migration, promoted apoptosis, and inhibited the PI3K/Akt pathway by targeting MET in PC cells. Our findings illustrated the specific molecular mechanism of miR-130b regulating PC progress. The miR-130b/MET axis may be an alternative target in the therapeutic intervention of PC and provide an opportunity to deepen our understanding of the pathogenesis of PC.

Contribution of a Circulating 2'-O-methylated MicroRNA Panel to the Diagnosis of Pancreatic Ductal Adenocarcinoma.

Background: We conducted an assessment of 2'-O-methylated (2'OMe) microRNAs (miRNAs) present in the circulation of individuals suffering from pancreatic ductal adenocarcinoma (PDAC). Subsequently, we devised a set of circulating 2'OMe miRNAs that can be utilized for the screening of PDAC patients within a group at increased risk. Methods: A four-step, multicenter research was carried out. The initial screening phase involved analyzing 10 samples from patients with pancreatic ductal adenocarcinoma (PDAC) and 10 specimens from donors who were in good health. RNA sequencing was performed on these specimens after pre-treatment via NaIO4. The instruction and confirmation phases involved the use of 2'OMe miRNA profiling and multivariate analysis to examine applicant 2'OMe miRNAs in a sample of 248 individuals. In a prospective registration population of 135 individuals, a clinical screening panel was created and confirmed. The performance of individual 2'OMe miRNAs or the biomarker panel was evaluated using the receiver operating characteristic curve. Results: Abnormal circulating 2'OMe miRNAs were detected in individuals suspected of pancreatic ductal adenocarcinoma (PDAC). A circulating panel of 3-2'OMe miRNAs, namely miR-28-3p, miR-143-3p, and miR-151a-3p, was subsequently identified. These miRNAs continually exhibited up-regulation in plasma samples of patients with pancreatic ductal adenocarcinoma (PDAC). The panel's area under the curve (AUC) was 1.0 in the experimental group and 0.928 in the verification cohort when comparing PDAC patients in all clinical stages to normal controls. During the application study, both the specificity and sensitivity were found to be 75.00% and 89.72% respectively, with an AUC value of 0.868. In the comparison between early-stage (I-II) PDAC patients and control subjects, the panel demonstrated an AUC of 1.0 in the training cohort and 0.924 in the validation population. In the application group the AUC was 0.810 (95% CI 0.729-0.876) in comparison to the high-risk symptomatic group. Conclusion: Abnormal circulating 2'OMe miRNAs were detected in individuals with pancreatic ductal adenocarcinoma (PDAC). Consequently, we devised a 2'OMe miRNA biological marker panel that holds promise as an initial detection tool for PDAC.

Comparison of OPPO Watch Sleep Analyzer and Polysomnography for Obstructive Sleep Apnea Screening.

Objective: To evaluate the clinical performance of the OPPO Watch (OW) Sleep Analyzer (OWSA) on OSA screening with polysomnography reference. Methods: We recruited 350 participants using OWSA and PSG simultaneously in a sleep laboratory. The respiratory event index (REI) derived from OWSA and the apnea-hypopnea index (AHI) provided by PSG were compared. SHapley Additive exPlanation (SHAP) values were calculated to explain the model of OWSA. Results: The OWSA-REI (26.5±18.5 events/h) correlated well with PSG-AHI (33.2±25.7 events/h; r = 0.91, p < 0.001), with an intraclass correlation coefficient (ICC) of 0.83. Using a threshold of AHI ≥15 events/h, the sensitivity, specificity, accuracy, and area under the curve (AUC) were 86.1%, 86.7%, 86.3%, and 0.94, respectively. Bland-Altman analysis showed that OWSA-REI and PSG-AHI were in good agreement (Mean Difference: -6.7, 95% CI:16.0 to -29.3 events/h). In addition, the effectiveness of the models in OWSA were also explained by visualizing SHAP values. Conclusion: The OWSA demonstrated a reasonable performance for OSA screening in the clinical setting. In light of this, it is possible for smartwatches to become a complementary tool to PSG, which is particularly useful for larger-scale preliminary screenings.

Microbiologic surveys for Baijiu fermentation are affected by experimental design.

The traditional Chinese alcoholic beverage Baijiu is produced by spontaneous fermentation of grains under anaerobic conditions. While numerous studies have used metagenomic technology to investigate the microbiome of Baijiu brewing, the microbial succession mechanism of Baijiu brewing has not been fully clarified, and metagenomic strategies for microecology surveys have not been comprehensively evaluated. Using the fermentation process of strong-flavor Baijiu as a model, we compared the data for bacterial communities based on short read 16S rRNA variable regions, V3-V4, and full-length 16S regions, V1-V9, to whole metagenomic shotgun sequencing (WMS) to measure the effect of technology selection on phylogenetic and functional profiles. The results showed differences in bacterial compositions and their relation to volatiles and physicochemical variables between sequencing methods. Furthermore, the percentage of V3-V4 sequences assigned to species level was higher than the percentage of V1-V9 sequences according to SILVA taxonomy, but lower according to NCBI taxonomy (P < 0.05). In both SILVA and NCBI taxonomies, the relative abundances of bacterial communities at both the genus and family levels were more positively correlated with WMS data in the V3-V4 dataset than in the V1-V9 dataset. The WMS identified changes in abundances of multiple metabolic pathways during fermentation (P < 0.05), including "starch and sucrose metabolism," "galactose metabolism," and "fatty acid biosynthesis." Although functional predictions derived from 16S data show similar patterns to WMS, most metabolic pathway changes are uncorrelated (P > 0.05). This study provided new technical and biological insights into Baijiu production that may assist in selection of methodologies for studies of fermentation systems.

Study on the Influence of Metal Substrates on Protective Performance of the Coating by EIS.

The degradation process of a red iron oxide epoxy coating on three kinds of metals under a periodic cycling exposure to 3.5 wt% NaCl solution (45 °C 12 h + 25 °C 12 h) was comparatively studied using electrochemical impedance spectroscopy (EIS), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction (XRD) methods. The influence of the metal substrates (carbon steel, brass, and Al alloy) on the protection performance of the coating was analyzed using variations in the electrochemical and chemical parameters. The failure criteria of the coating were discussed. The results show that the coating on the three substrates presents different failure times, with the coating on steel presenting the shortest time and the coating on Al alloy the longest time. The characteristics of metal substrates and their corrosion products influence the coating failure behavior. The corrosion products with loose and hygroscopic properties of steel and brass have promoting effects on the diffusion of water through the coating. The passive film of the Al alloy substrate and the formation of salt film containing Cl- have corrosion-inhibiting effects on the substrate. Evaluation of the coating performance by |Z|0.01Hz should consider the characteristics of the metal substrates.

Design, Synthesis, and Biological Evaluation of Thioglucoside Analogues of Gliflozin as Potent New Gliflozin Drugs.

In this study, we have investigated the potential of two classes of thioglucoside analogues of gliflozins as antidiabetic drugs, one with substitutions of S-atoms in meta-positions (similar to C-glucoside SGLT2 inhibitors, TAGs A, B, and C) and the other with substitutions of S-atoms in ortho-positions (similar to O-glucoside SGLT2 inhibitors, TAGs D, E, F, and G). These TAGs were confirmed to show good stability against ß-glucosidase and to have no acute toxicity to cultured cells. Most importantly, TAGs D, E, F, and G all showed high inhibitory activity against SGLT2 (IC50: 2.0-5.9 nM) and thus have great potential to be developed as new gliflozin drugs. Compared with the synthesis of C-glucoside gliflozins, the synthesis of TAGs is simple, efficient, and associated with low costs, high yields, and very mild reaction conditions.

Improved the Impact of SST for HY-2A Scatterometer Measurements by Using Neural Network Model.

The variation of sea surface temperature (SST) can change the backscatter coefficient measured by a scatterometer, resulting in a decrease in the accuracy of the sea surface wind measurement. This study proposed a new approach to correct the effect of SST on the backscatter coefficient. The method focuses on the Ku-band scatterometer HY-2A SCAT, which is more sensitive to SST than C-band scatterometers, can improve the wind measurement accuracy of the scatterometer without relying on reconstructed geophysical model function (GMF), and is more suitable for operational scatterometers. Through comparisons to WindSat wind data, we found that the Ku-band scatterometer HY-2A SCAT wind speeds are systemically lower under low SST and higher under high SST conditions. We trained a neural network model called the temperature neural network (TNNW) using HY-2A data and WindSat data. TNNW-corrected backscatter coefficients retrieved wind speed with a small systematic deviation from WindSat wind speed. In addition, we also carried out a validation of HY-2A wind and TNNW wind using European Center for Medium-Range Weather Forecasts (ECMWF) reanalysis data as a reference, and the results showed that the retrieved TNNW-corrected backscatter coefficient wind speed is more consistent with ECMWF wind speed, indicating that the method is effective in correcting SST impact on HY-2A scatterometer measurements.

Associations of Gastrointestinal Tract Tumor Necrosis Factor Receptor-Associated Factor 6 Expression with Clinical Features and Prognosis of Eosinophilic Gastroenteritis.

BACKGROUND: Few studies have been conducted to explore the expression of tumor necrosis factor receptor-associated factor 6 in eosinophilic gastroenteritis patients. Therefore, the expression profile of tumor necrosis factor receptor-associated factor 6 in the gastrointestinal tract of eosinophilic gastroenteritis patients and its associations with clinical features were explored in this study. METHODS: Thirty-four eosinophilic gastroenteritis patients who presented in Ruijin Hospital from December 2012 to May 2019 and had accepted gastrointestinal endoscopic examinations were recruited. Medical records and endoscopic biopsies were collected, and the prognosis was followed up by telephone. Healthy persons were selected as the control group. Hematoxylin and eosin and immunohistochemical staining were performed in both eosinophilic gastroenteritis patients and healthy persons. The final results were analyzed by skilled pathologists, and mean optical density values of tumor necrosis factor receptor-associated factor 6 were calculated by Image J software. Final results were analyzed by Statistical Package for the Social Sciences software 22.0. RESULTS: Thirty-four patients (mean age: 25.56 ± 21.14 years, 61.76% males) were recruited for this study. There was no significant difference in tumor necrosis factor receptor-associated factor 6 mean optical density values of gastric tissues in eosinophilic gastroenteritis patients and healthy people (0.22 ± 0.16 vs. 0.14 ± 0.05, P > .05). Eosinophilic gastroenteritis patients had a significantly lower level of intestinal tumor necrosis factor receptor-associated factor 6 mean optical density values than that of healthy people (0.16 ± 0.05 vs. 0.23 ± 0.06, P < .05). Intestinal tumor necrosis factor receptor-associated factor 6 mean optical density values negatively linearly correlated with serum interleukin-10 level (r = -0.618, P = .043 < .05). There were no differences between eosinophilic gastroenteritis patients with or without relapse regarding the expression level of intestinal tumor necrosis factor receptor-associated factor 6 (P = .227 > .05). CONCLUSION: Patients with eosinophilic gastroenteritis might have a deficiency of intestinal tumor necrosis factor receptor-associated factor 6 compared to healthy controls.

Variation in microbiological heterogeneity in Chinese strong-flavor Baijiu fermentation for four representative varieties of sorghum.

The quality and composition of strong-flavor Baijiu (SFB), a type of Chinese liquor, depends on the variety of sorghum used in fermentation. However, comprehensive in situ studies measuring the effects sorghum varieties on the fermentation are lacking and the underlying microbial mechanisms remains poorly understood. We studied the in situ fermentation of SFB by using metagenomic, metaproteomic, and metabolomic techniques across four sorghum varieties. Sensory characteristics were best for SFB made from glutinous variety Luzhouhong, followed by glutinous hybrid Jinnuoliang and Jinuoliang, and those made with non-glutinous Dongzajiao. In agreement with sensory evaluations, the volatile composition of SFB samples differed between sorghum varieties (P < 0.05). Fermentation of different sorghum varieties varied in microbial diversity, structure, volatile compounds, and physicochemical properties (pH, temperature, starch, reducing sugar, and moisture) (P < 0.05), with most changes occurring within the first 21 days. Additionally, the microbial interactions and their relationship with volatiles, as well as the physicochemical factors that govern microbial succession, differed between varieties of sorghum. The number of physicochemical factors affecting bacterial communities outweighed those affecting fungal communities, suggesting that bacteria were less resilient to the brewing conditions. This correlates with the finding that bacteria play a major role in the differences in microbial communities and metabolic functions during fermentation with the different varieties of sorghum. Metagenomic function analysis revealed differences in amino acid and carbohydrate metabolism between sorghum varieties throughout most of the brewing process. Metaproteomics further indicated most differential proteins were found in these two pathways, related to differences in volatiles between sorghum varieties of Baijiu and originating from Lactobacillus. These results provide insight into the microbial principles underlying Baijiu production and can be used to improve the quality of Baijiu by selecting the appropriate raw materials and optimizing fermentation parameters.

Degradation of Carbon Fiber-Reinforced Polymer Composites in Salt Water and Rapid Evaluation by Electrochemical Impedance Spectroscopy.

The electrochemical impedance spectroscopy and weight gain tests were performed on carbon fiber/vinyl ester and carbon fiber/bismaleimide composites in 3.5% NaCl solution to study the electrochemical and water absorption behaviors. The microstructure morphology and the flexural property of the composites in the long-term exposure process were analyzed with the scanning electron microscope and four-point bending tests. The results revealed that after long-time immersion (>200 d), the water absorption of the two composites is less than 0.5%. This has little effect on the microstructural integrity, only with slight damage on the fiber/resin interfaces, but results in a significant decrease (about 84%) in the composite flexural property. The variation of the water absorption percentage shows good consistency with that of the resin capacitance (Qc) and is negatively related to the variation of the resin resistance (Rpo) and the low-frequency impedance (|Z|0.01Hz) of the composites. A good linear relationship exists between the variations of phase angles in the middle-frequency range (0.1-10 Hz) and the |Z|0.01Hz. The phase angle at 10 Hz (θ10Hz) may be suggested as a suitable parameter to rapidly evaluate the performance of carbon fiber-reinforced polymer composites, just like for evaluating the protective performance of polymer-coated metals in the literature.

Analysis of clinical characteristics of centrally mediated abdominal pain syndrome, exploration of diagnostic markers and its relationship with the efficacy of duloxetine treatment.

INTRODUCTION: Centrally mediated abdominal pain syndrome (CAPS) is characterized by severe abdominal pain. Diagnosis of CAPS is still an exclusionary diagnosis, there remain no effective diagnostic biomarkers so far. Duloxetine is the major pharmacotherapy of CAPS, while some CAPS patients do not respond to duloxetine treatment. However, there is a lack of molecular markers to predict the efficacy of duloxetine. In our pilot study, we have found differential expression profiles of serum miRNAs between CAPS patients and healthy controls. Our study aims to explore the clinical characteristics, specific miRNAs in serum as diagnostic biomarkers of CAPS and predictive biomarkers of the efficacy of duloxetine. METHODS/DESIGN: In this prospective cohort study, we plan to enroll 430 participants including 215 CAPS patients and 215 healthy controls. The CAPS group takes duloxetine 30 mg per day as an initial dose. Patients will have 24-week medication period and follow up at week 0, 4, 12, 24 and 36. Blood samples will be obtained from patients at every visits and health controls at the initial visit and a series of questionnaires will be completed by the participants. The primary end points are: The differential expression of miRNAs between CAPS groups and healthy control groups at baseline. The changes in abdominal pain scores before and after duloxetine treatment in patients with CAPS and their relationship with the changes in miRNAs. The secondary end point is the changes in scores of depression, anxiety, sleep quality and quality of life before and after duloxetine treatment in patients with CAPS and their relationship with changes in miRNAs. DISCUSSION: Findings of study will provide the reliable basis for diagnosis and the predictor of duloxetine efficacy of CAPS. Importantly, findings grant patients a chance to benefit from treatment.

Bioremediation of degraded pit mud by indigenous microbes for Baijiu production.

Microbes in pit mud play key roles in fermentation cellars for Chinese strong-flavor Baijiu (SFB) production. Pit mud, however, is frequently degraded during production, compromising the quality of the end product. In this study, a bioremediation method was used to restore degraded pit mud (DPM) using indigenous microbes derived from SFB production. Metabolomics and metagenomics were used to determine the dynamics of prokaryotes during DPM restoration and their link to SFB production. The composition of flavor compounds in SFB changed (P = 0.0001) before and after restoration of DPM. Consistent with the improved sensory quality, the ethyl caproate/ethyl lactate ratio, an SFB quality measure, increased after restoration (P < 0.001). The concentrations of humus, NH4+, available phosphorus, and available potassium in DPM increased during the restoration process (P < 0.05), which is consistent with high-quality pit mud. The relative abundance of microbes that are beneficial to SFB fermentation, such as Caproiciproducens, a bacterium that produces caproic acid, increased during the restoration process. Furthermore, a total of 18 metabolic pathways were enriched (P < 0.05) from DPM before and after restoration. This includes butanoate metabolism and pyruvate metabolism, which are related to the synthesis of key flavor esters in SFB.

Network pharmacology approach to investigate the multitarget mechanisms of Zhishi Rhubarb Soup on acute cerebral infarction.

CONTEXT: Zhishi Rhubarb Soup (ZRS) is a traditional Chinese medicine formula used in the clinic to treat acute cerebral infarction (ACI) for many years. However, the exact mechanism of the treatment remains unclear. OBJECTIVE: This study elucidates the multitarget mechanisms underlying the effects of ZRS on ACI using network pharmacology analysis and verify its effect by performing animal experiments. MATERIALS AND METHODS: Using the network pharmacology approach, the multiple components, critical targets and potential mechanisms of ZRS against ACI were investigated. Six herbal names of ZRS and 'acute cerebral infarction' were used as keywords to search the relevant databases. In addition, we established the MCAO model to verify the results of network pharmacology enrichment analysis. ZRS (10 g crude drug/kg) was gavaged once per day for 7 consecutive days beginning 3 h after model establishment. After ZRS treatment, TTC staining, Western blot analysis, IHC and ELISA were conducted to further explore the mechanism of ZRS intervention in ACI. RESULTS: The network pharmacology approach identified 69 key targets, 10 core genes and 169 signalling pathways involved in the treatment of ACI with ZRS. In vivo experiment showed that ZRS treatment significantly reduced cerebral infarction volume (42.76%). It also reduced the expression level of AGE, RAGE and P65; and inhibited the expression of inflammatory MMP-9 and IFN-γ. CONCLUSIONS: This study demonstrated that ZRS improved cerebral ischaemic injury by inhibiting neuroinflammation partly via the AGE-RAGE signalling pathway. It provides a theoretical basis for the clinical application of ZRS in the treatment of ACI.

Effect of HAc on the Metastable Pitting Corrosion of 304 SS in NaCl Solution.

Stainless steels (SSs) easily suffer localized corrosion damage, such as pitting corrosion, in mixed solutions of acetic acid and sodium chloride. Currently, few works have been focused on the early stages of the pitting corrosion (metastable pitting corrosion) process of SSs in a chloride-HAc mixture solution. In this work, the effects of acetic acid (HAc) and its concentration on metastable pitting corrosion and the uniform corrosion of 304 SS in 0.6 mol/L NaCl solution were investigated by a slow-scanning potentiodynamic polarization test, scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). The results show that the uniform corrosion rate of 304 SS increases after HAc addition but, with an increase in HAc concentration, the corrosion rate decreases. In the presence of HAc, the metastable pitting potential (Em) and stable pitting potential (Eb) move negatively, but the number of metastable pits notably decreases. HAc has a promoting action on the growth rate of the metastable pits and facilitates the transition from metastable pits to stable pits. The influence of HAc is related to a decrease in solution pH and the chemical adsorption of HAc.

Development and application of a new sensitivity analysis model for the remote sensing retrieval of heavy metals in water.

This work proposes a new sensitivity analysis model, referred to as the D-δ(ε) model, for the remote sensing retrieval of heavy metals in bodies of water. By defining the reflectance ratio function (δ(ε)), we deduce the mathematical relationships between the heavy metal concentration sequences (Di) that can be effectively used for remote sensing retrievals and the radiometric resolution (ε) of the remote sensing instrument. Then, as a function of wavelength, we obtain the curve of the lower limit of the heavy metal concentrations in water that can be retrieved by remote sensing. To demonstrate the advantages of this model, we take two compounds, copper sulphate (CuSO4) and cadmium sulphide (CdS), as examples to discuss the remote sensing sensitivity of different wavelengths when retrievals are performed using the Chinese HJ-1A's hyperspectral imager (HSI). The results showed that the lowest detectable concentration of CuSO4 in the wavelength range of 460.04-496 nm (corresponding to bands 1-17 of the HSI image) can be below 0.15 mg/L, while the concentration of CdS can be lower than 0.001 mg/L in the separate ranges of 460.04-493.59 nm (bands 1-16) and 526.885-594.79 nm (bands 29-51). This model clearly demonstrates the mathematical relationship obeyed by "D-ε". Additionally, this model can not only calculate the retrieval concentration sequences at any observation wavelength but also intuitively provide the curve of the lower concentration limit for heavy metal retrievals. This work provides a theoretical basis for the selection of the most sensitive bands for remote sensing retrieval using hyperspectral images in the future.

Zr4+-Doped Anatase TiO2 Nanotube Array Electrode for Electrocatalytic Reduction of L-cystine.

A Zr4+-doped anatase TiO2 nanotube array electrode was prepared using a process that included Ti anodizing, chemical immersion, and heat treatment. The compositions, microstructure, and electrochemical properties of the prepared electrodes were characterized. The results show that Zr4+ was successfully introduced into the TiO2 nanotube array electrodes. Because Zr4+ was doped into the crystal structure of the TiO2and replaced a part of Ti4+ to form more oxygen vacancies and Ti3+, the electrocatalytic activity of the prepared electrodes, for the reduction of L-cystine, was significantly improved.

Structural and Functional Changes in Prokaryotic Communities in Artificial Pit Mud during Chinese Baijiu Production.

The Chinese alcoholic beverage strong-flavor baijiu (SFB) gets its characteristic flavor during fermentation in cellars lined with pit mud. Microbes in the pit mud produce key precursors of flavor esters. The maturation time of natural pit mud of over 20 years has promoted attempts to produce artificial pit mud (APM) with a shorter maturation time. However, knowledge about the molecular basis of APM microbial dynamics and associated functional variation during SFB brewing is limited, and the role of this variability in high-quality SFB production remains poorly understood. We studied APM maturation in new cellars until the fourth brewing batch using 16S rRNA gene amplicon sequencing, quantitative PCR, metaproteomics, and metabolomics techniques. A total of 36 prokaryotic classes and 195 genera were detected. Bacilli and Clostridia dominated consistently, and the relative abundance of Bacilli decreased along with the APM maturation. Even though both amplicon sequencing and quantitative PCR showed increased abundance of Clostridia, the levels of most of the Clostridium proteins were similar in both the first- and fourth-batch APM samples. Six genera correlated with eight or more major flavor compounds in SFB samples. Functional prediction suggested that the prokaryotic communities in the fourth-batch APM samples were actively engaged in organic acid metabolism, and the detected higher concentrations of proteins and metabolites in the corresponding metabolic pathways supported the prediction. This multi-omics approach captured changes in the abundances of specific microbial species, proteins, and metabolites during APM maturation, which are of great significance for the optimization of APM culture technique.IMPORTANCE Strong-flavor baijiu (SFB) accounts for more than 70% of all Chinese liquor production. In the Chinese baijiu brewing industry, artificial pit mud (APM) has been widely used since the 1960s to construct fermentation cellars for production of high-quality SFB. To gain insights at the systems level into the mechanisms driving APM prokaryotic taxonomic and functional dynamics and into how this variation is connected with high-quality SFB production, we performed the first combined metagenomic, metaproteomic, and metabolomic analyses of this brewing microecosystem. Together, the multi-omics approach enabled us to develop a more complete picture of the changing metabolic processes occurring in APM microbial communities during high-quality SFB production, which will be helpful for further optimization of APM culture technique and improvement of SFB quality.

CRISPR/Cas9 Genome Engineering in Engraftable Human Brain-Derived Neural Stem Cells.

Human neural stem cells (NSCs) offer therapeutic potential for neurodegenerative diseases, such as inherited monogenic nervous system disorders, and neural injuries. Gene editing in NSCs (GE-NSCs) could enhance their therapeutic potential. We show that NSCs are amenable to gene targeting at multiple loci using Cas9 mRNA with synthetic chemically modified guide RNAs along with DNA donor templates. Transplantation of GE-NSC into oligodendrocyte mutant shiverer-immunodeficient mice showed that GE-NSCs migrate and differentiate into astrocytes, neurons, and myelin-producing oligodendrocytes, highlighting the fact that GE-NSCs retain their NSC characteristics of self-renewal and site-specific global migration and differentiation. To show the therapeutic potential of GE-NSCs, we generated GALC lysosomal enzyme overexpressing GE-NSCs that are able to cross-correct GALC enzyme activity through the mannose-6-phosphate receptor pathway. These GE-NSCs have the potential to be an investigational cell and gene therapy for a range of neurodegenerative disorders and injuries of the central nervous system, including lysosomal storage disorders.

Contrasting bacterial community structure in artificial pit mud-starter cultures of different qualities: a complex biological mixture for Chinese strong-flavor Baijiu production.

The complex starter culture for artificial pit mud (APMSC) hosts a wide variety of microbial communities that play a crucial role in Chinese strong-flavor Baijiu production. Based on its organoleptic properties, the quality of APMSC can be divided into normal and inferior quality grades. However, the relationship between the APMSC microbial community and APMSC quality is poorly understood. In this study, the bacterial community structure in normal and inferior APMSC derived from two different production batches was analyzed using denaturing gradient gel electrophoresis and Illumina MiSeq sequencing. Highly similar patterns of bacterial diversity and community structure were observed in the APMSC samples of the same quality, and a significant higher bacterial species diversity (Shannon index and Chao1) was detected in the normal compared to the inferior APMSC samples. Fifteen genera were detected in the APMSC samples, and seven (Caproiciproducens, Clostridium, Lactobacillus, Bacillus, Pediococcus, Rummeliibacillus, and Sporolactobacillus) were dominant, accounting for 92.12-99.89% of total abundance. Furthermore, the bacterial communities in the normal and inferior APMSC had significantly different structure and function. The normal APMSC was characterized by abundant Caproiciproducens and Clostridium and high caproic and butyric acid contents. In contrast, the inferior APMSC was overrepresented by Lactobacillus and Bacillus and lactic and acetic acids. This study may help clarify the key microbes sustaining APMSC ecosystem stability and functionality, and guide future improvements in APMSC production.

Bilateral vs. unilateral endoscopic ultrasound-guided celiac plexus neurolysis for abdominal pain management in patients with pancreatic malignancy: a systematic review and meta-analysis.

CONTEXT: Endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) by bilateral or unilateral approach is widely used in palliative abdominal pain management in pancreatic cancer patients, but the analgesic effect and relative risks of the two different puncture routes remain controversial. OBJECTIVES: The aim of this systematic review was to evaluate the analgesic efficacy and safety of bilateral EUS-CPN compared with unilateral EUS-CPN. METHODS: An electronic database search was performed for randomized controlled trials comparing bilateral and unilateral approaches of EUS-CPN using the Pubmed, Cochrane Library, Web of Science, Google Scholar, and CNKI databases. Meta-analysis was performed using RevMan 5.3 after screening and methodological evaluation of the selected studies. Outcomes included pain relief, treatment response, analgesic reduction, complications, and quality of life (QOL). RESULTS: Six eligible studies involving 437 patients were included. No significant difference was found in short-term pain relief [SMD = 0.31, 95% CI (- 0.20, 0.81), P = 0.23] and response to treatment [RR = 0.99, 95% CI (0.77, 1.41), P = 0.97] between the bilateral and unilateral neurolysis groups. However, only the bilateral approach was associated with a statistically significant reduction in the postoperative use of analgesics [RR = 0.66, 95% CI (0.47, 0.94), P = 0.02] compared to the unilateral approach. A descriptive analysis was performed for complications and QOL. CONCLUSION: The short-term analgesic effect and general risk of bilateral EUS-CPN are comparable with those of unilateral EUS-CPN, but our evidence supports the conclusion that the bilateral approach significantly reduces postoperative analgesic use.