Characterization and correlation of dominant bacteria and volatile compounds in post-fermentation process of Ba-bao Douchi.

Ba-bao Douchi, traditionally produced and spontaneously fermented for 1-2 years, has a unique flavor. However, little information is known about microorganisms and volatile flavors, particularly their relationship. In this study, the aroma profiles including the key aroma compounds, and bacterial communities were characterized and the correlations between dominant bacterial genera with key aroma compounds were studied during the post-fermentation of Ba-bao Douchi. The research showed that 12 bacterial genera were identified as the dominant genus by high-throughput sequencing. A total of 84 volatile compounds were detected by HS-GC-IMS and HS-SPME-GC-MS. Odor activity value (OAV) and gas chromatography-Mass spectrometry-olfactometry (GC-MS-O) were combined to determine the key volatile compounds, and the main volatile compounds including ethyl hexanoate, ethyl heptanoate, isovaleraldehyde, (+)-α-pinene, beta-phellandrene, were found to be responsible for the strong fruitiness, chocolate fragrance, fresh scent flavor, and ginger flavor of Ba-bao Douchi. Pearson correlation analysis showed that 5 dominant bacterial genera were positively associated with > 6 key volatile compounds (p < 0.01, |r| > 0.7). Thus, these bacterial genera might have an effect on the biosynthesis of volatile components. This study provides a theoretical reference for revealing the functional microorganisms and improving the flavor quality of Ba-bao Douchi.

Single-Cell Transcriptomics-Based Study of Transcriptional Regulatory Features in the Non-Obstructive Azoospermia Testis.

Non-obstructive azoospermia (NOA) is one of the most important causes of male infertility. Although many congenital factors have been identified, the aetiology in the majority of idiopathic NOA (iNOA) cases remains unknown. Herein, using single-cell RNA-Seq data sets (GSE149512) from the Gene Expression Omnibus (GEO) database, we constructed transcriptional regulatory networks (TRNs) to explain the mutual regulatory relationship and the causal relationship between transcription factors (TFs). We defined 10 testicular cell types by their marker genes and found that the proportion of Leydig cells (LCs) and macrophages (tMΦ) was significantly increased in iNOA testis. We identified specific TFs including LHX9, KLF8, KLF4, ARID5B and RXRG in iNOA LCs. In addition, we found specific TFs in iNOA tMΦ such as POU2F2, SPIB IRF5, CEBPA, ELK4 and KLF6. All these identified TFs are strongly engaged in cellular fate, function and homeostasis of the microenvironment. Changes in the activity of the above-mentioned TFs might affect the function of LCs and tMΦ and ultimately cause spermatogenesis failure. This study illustrate that these TFs play important regulatory roles in the occurrence and development of NOA.

Multi- and transgenerational biochemical effects of low-dose exposure to bisphenol A and 4-nonylphenol on testicular interstitial (Leydig) cells.

Bisphenol A (BPA) and 4-nonylphenol (NP) are well-known endocrine-disrupting chemicals (EDCs) that have been proven to affect Leydig cell (LC) functions and testosterone production, but whether BPA and NP have multi- and transgenerational biochemical effects on Leydig cells (LCs) is unknown. Fourier transform infrared (FTIR) spectroscopy is a powerful analytical technique that enables label-free and non-destructive analysis of the tissue specimen. Herein we employed FTIR coupled with chemometrics analysis to identify biomolecular changes in testicular interstitial (Leydig) cells of rats after chronic exposure to low doses of BPA and NP. Cluster segregations between exposed and control groups were observed based on the fingerprint region of 1800-900 cm-1 in all generations. The main biochemical alterations for segregation were amide I, amide II and nucleic acids. BPA and NP single and co-exposure induced significant differences in the ratio of amide I to amide II compared to the corresponding control group in all generations. BPA exposure resulted in remarkable changes of cellular gene transcription and DNA oxidative damage across all generations. Direct exposure to BPA, NP, and BPA&NP of F0 and F1 generations could significantly decrease lipid accumulation in LCs in the F2 and F3 generations. The overall findings revealed that single or co-exposure to BPA and NP at environmental concentrations affects the biochemical structures and properties of LCs.

Erythromycin inhibits cigarette smoke-induced inflammation through regulating the PPARγ/NF-κB signaling pathway in macrophages.

Chronic obstructive pulmonary disease is characterized by chronic inflammation of the airway and lungs. Accumulating evidence has suggested that erythromycin (EM) plays a protective role against cigarette smoke-induced oxidative stress and the inflammatory response. However, the underlying mechanisms remain relatively unclear. The present study aimed to investigate the role of EM in inhibiting cigarette smoke-induced inflammation in human macrophages and its potential mechanism. A Cell Counting Kit-8 assay was used to determine the optimum concentration of EM and cigarette smoke extract (CSE) and it was found that 0.1 and 1% CSE and 0.1, 1.0 and 10 µg/ml EM exerted no significant effect on the cell proliferation activity, whereas 2 and 3% CSE exerted a significant inhibitory effect over the cell proliferation activity. We observed that 10 µmol/ml GW9662 (A PPARγ antagonist) and the presence of 1% CSE could promote the expression and activation of NF-κB p65. And this increased the expression of IL-6, IL-8 and reactive oxygen species (ROS). At the same time, 10 µmol/ml GW9662 and 1% CSE was found to inhibit the expression and activation of peroxisome proliferator activated receptors γ (PPARγ); However, 1 µg/ml EM was discovered to reverse these effects. Co-immunoprecipitation subsequently discovered an interaction between PPARγ and NF-κB p65. In conclusion, the present study suggested that EM may reduce the damage of PPARγ by inhibiting oxidative stress and reducing the expression of ROS and finally relieving cigarette smoke-induced inflammation through the PPARγ/NF-κB signaling pathway in macrophages.

Changing trends in the bacteriological profiles and antibiotic susceptibility in neonatal sepsis at a tertiary children's hospital of China.

BACKGROUND: Sepsis is a major cause of neonatal morbidity and mortality in developing countries, and early-onset sepsis has poor outcomes. The causative bacteria vary depending on the geographical location of the hospital. This study aimed to determine the changing trends of causative bacteria and antibiotic susceptibility in the past decade. METHODS: This study retrospectively analyzed the blood culture of positive cases of early-onset sepsis admitted to the neonatal intensive care unit of our hospital between 2009 and 2018. The cases were divided into two phases, i.e., phase I (2009 to 2013) and phase II (2014 to 2018). Changing trends in the bacteriological profiles and antibiotic susceptibility were recorded and analyzed. RESULTS: A total of 1,479 causative bacteria were detected. Gram-positive bacteria were isolated in 74.92% of the cases, and coagulase-negative Staphylococci (CoNS) (63.22%) was identified as the common isolate. Klebsiella pneumoniae (10.01%) followed by Escherichia coli (8.72%) were the dominant Gram-negative bacteria. Comparative analysis showed a significant reduction in CoNS. Among Gram-negative bacteria, K. pneumoniae was initially predominant but was replaced by E. coli in phase II. Gram-positive bacteria showed relatively high susceptibility to aminoglycosides and quinolones. K. pneumoniae exhibited higher resistance to cephalosporin compared with E. coli. Reduced sensitivity against the first- and second-generation antibiotics was observed in phase II. CONCLUSIONS: The etiological profile of neonatal sepsis (NS) has undergone a significant change in the last decade. Antibiotic resistance has increased, and continuous surveillance for antibiotic susceptibility is required to ensure efficient therapeutic outcomes.

Erythromycin Regulates Cigarette Smoke-Induced Proinflammatory Mediator Release Through Sirtuin 1-Nuclear Factor κB Axis in Macrophages and Mice Lungs.

BACKGROUND: Macrolides have anti-inflammatory and antioxidative stress function, but their pharmacological regulation remains unclear. Sirtuin 1 (SIRT1) is redox-sensitive protein belongs to class III histone/protein deacetylases, SIRT1 regulates the acetylation/expression of nuclear factor κB (NF-κB) and is involved in the airway inflammation of chronic obstructive pulmonary disease. OBJECTIVES: The present study was designed to examine the effects of erythromycin (EM) on the SIRT1-NF-κB axis and NF-κB-dependent proinflammatory cytokines. METHODS: Human macrophages were preincubated with EM and then treated with cigarette smoke extract (CSE). The mice were treated by injecting drugs to gastric with EM before cigarette smoke exposure. Reactive oxygen species (ROS) released by treated human macrophages were detected using flow cytometry. The expression of SIRT1 and NF-κB was analyzed by western blotting. SIRT1 and the RelA/p65 subunits of NF-κB interaction were detected by coimmunoprecipitation. We found that EM suppressed CSE-induced ROS released in human macrophages, which coincided with increases in SIRT1 protein expression in the macrophages and lungs of mice, resulting in suppressed -NF-κB acetylation and expression correlated with a reduction of inflammatory mediators. CONCLUSION: These findings suggest that EM increased SIRT1, leading to acetylation/expression of NF-κB, and thereby decreasing cigarette smoke-driven NF-κB-dependent proinflammatory cytokine.

Interactions among lncRNAs, miRNAs and mRNA in colorectal cancer.

Long non-coding RNAs (lncRNAs) are longer than 200 nts non-coding transcripts and have recently emerged as one of the largest and significantly diverse RNA families whereas microRNAs (miRNAs) are highly conserved short single-stranded ncRNAs (∼18-22 nucleotides). As families of small and long evolutionarily conserved ncRNAs, lncRNAs activate and repress genes via a variety of mechanisms at both transcriptional and translational levels, while miRNAs regulate protein-coding gene expression mainly through mRNA degradation or silencing, These ncRNAs have been proved to be involved in multiple biological functions, such as proliferation, differentiation, migration, angiogenesis and apoptosis. Today, while majority of studies have focused on defining the regulatory functions of lncRNAs and miRNAs, limited information have now available for the mutual regulations of lncRNAs, miRNAs and mRNA. Thus, the underlying molecular mechanisms, in particularly the interactions among lncRNAs, miRNAs and mRNA in development, growth, metastasis and therapeutic potential of cancer still remain obscure. Colorectal cancer (CRC) is known as the third most common and fourth leading cancer death worldwide. Increasing evidence showed the close correlations among aberrant expressions of lncRNAs, miRNAs and the occurrence, development of CRC. This review summarize the potential links among these RNAs in following three areas: 1, The biogenesis and roles of miRNAs in CRC; 2, The biogenesis and functions of lncRNAs in CRC; 3, The interactions among lncRNAs, miRNAs and mRNA in tumorigensis, growth, progression, EMT formation, chemoradiotherapy resistance, and therapeutic potential in CRC. We believe that identifying diverging lncRNAs, miRNAs and relevant genes, their interactions and complex molecular regulatory networks will provide important clues for understanding the mechanism and developing novel diagnostic and therapeutic strategies for CRC. Further efforts are warranted to bring the promise of regulating their activities into clinical utilities.

Neuroprotective effects of autophagy inhibition on hippocampal glutamate receptor subunits after hypoxia-ischemia-induced brain damage in newborn rats.

Autophagy has been suggested to participate in the pathology of hypoxic-ischemic brain damage (HIBD). However, its regulatory role in HIBD remains unclear and was thus examined here using a rat model. To induce HIBD, the left common carotid artery was ligated in neonatal rats, and the rats were subjected to hypoxia for 2 hours. Some of these rats were intraperitoneally pretreated with the autophagy inhibitor 3-methyladenine (10 mM in 10 µL) or the autophagy stimulator rapamycin (1 g/kg) 1 hour before artery ligation. Our findings demonstrated that hypoxia-ischemia-induced hippocampal injury in neonatal rats was accompanied by increased expression levels of the autophagy-related proteins light chain 3 and Beclin-1 as well as of the AMPA receptor subunit GluR1, but by reduced expression of GluR2. Pretreatment with the autophagy inhibitor 3-methyladenine blocked hypoxia-ischemia-induced hippocampal injury, whereas pretreatment with the autophagy stimulator rapamycin significantly augmented hippocampal injury. Additionally, 3-methyladenine pretreatment blocked the hypoxia-ischemia-induced upregulation of GluR1 and downregulation of GluR2 in the hippocampus. By contrast, rapamycin further elevated hippocampal GluR1 levels and exacerbated decreased GluR2 expression levels in neonates with HIBD. Our results indicate that autophagy inhibition favors the prevention of HIBD in neonatal rats, at least in part, through normalizing GluR1 and GluR2 expression.

Rheological and functional properties of composite sweet potato - wheat dough as affected by transglutaminase and ascorbic acid.

Effect of transglutaminase (TGM) and ascorbic acid (AA) on composite sweet potato - wheat dough functional and rheological properties was studied. Partial substitution of wheat flour with sweet potato flour at the level of 20 % significantly (P ≤ 0.05) reduced glutenin, gliadin, dough stability, protein weakening, storage modulus (G') and viscous modulus (G″). Mixolab revealed that both TGM and AA treated dough had stability and protein weakening closed to wheat dough (control), with TGM treated dough having the highest values. TGM Introduced new cross-link bonds as shown by the change of amino acid concentration, leading to an increase in storage modulus (G') and viscous modulus (G″), with G' being higher at all levels of TGM concentration. The opposite was observed for composite dough treated with AA as measured by controlled - stress rheometer. TGM treatment increased glutenin and gliadin content. Compared with the control, dough treated with AA exhibited high molecular weight of polymers than TGM treated dough. The results indicate that the TGM and AA modification of the mixolab and dynamic rheological characteristics (G' and G″) dependent on the changes of GMP, glutenin, gliadin and protein weakening in the composite dough. TGM and AA treatment could improve functional and rheological properties of sweet potato - wheat dough to levels that might be achieved with normal wheat bread. However, it's extremely important to optimize the concentrations of both additives to obtain the optimum response.

Calcium-permeable AMPA receptors in neonatal hypoxic-ischemic encephalopathy (Review).

Hypoxic-ischemic encephalopathy (HIE) is an important cause of brain injury in the newborn and may result in long-term devastating consequences. Excessive stimulation of glutamate receptors (GluRs) is a pivotal mechanism underlying ischemia-induced selective and delayed neuronal death. Although initial studies focused on N-methyl-D-aspartic acid (NMDA) receptors as critical mediators in HIE, subsequent studies supported a more central role for α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs), particularly Ca2+-permeable AMPARs, in brain damage associated with hypoxia-ischemia. This study reviewed the important role of Ca2+-permeable AMPARs in HIE and the future potential neuroprotective strategies associated with Ca2+-permeable AMPARs.

[Changes in public health awareness of traditional Chinese medicine in Shanghai in the late Qing Dynasty].

Public health awareness existed in the practice of traditional Chinese medicine (TCM) long ago. In the process of Shanghai's modernization and in competition with Western medicine, TCM in Shanghai has gradually accepted the modern public health awareness, fostering its strengths, circumventing its weaknesses and playing an important role in the local public health service. To study the vicissitude of TCM public health awareness at this time will be helpful to further understand the modern history of TCM and also provide useful reference for further participation of TCM in modern public health enterprise. In this paper, the authors used literature analysis and historical research to analyze the medical practice and writings of representative TCM practitioners, medical groups and journals. The results showed that the public health awareness of TCM in Shanghai has evolved from its traditional pattern to the modern pattern seen today; the traditional pattern was characterized by individual health care and some degree of medical collaboration, whereas the modern pattern is characterized by public health education. This process was propelled forward throughout by intense national spirit. TCM has made significant contributions to the local public health service in Shanghai in the late Qing Dynasty, which promoted the modernization of public health awareness of TCM in the People's Republic of China. The authors also found that one of the ways of modernizing TCM is to diversify the ways of publicizing TCM and make it easily understood, which can shed a new light on promoting the development of TCM.