S-Propargyl-Cysteine Ameliorates Peripheral Nerve Injury through Microvascular Reconstruction.

Microvascular reconstruction is essential for peripheral nerve repair. S-Propargyl-cysteine (SPRC), the endogenous hydrogen sulfide (H2S) donor, has been reported to promote angiogenesis. The aim of this study is to utilize the pro-angiogenic ability of SPRC to support peripheral nerve repair and to explore the potential mechanisms. The effects and mechanisms of SPRC on angiogenesis and peripheral nerve repair were examined under hypoxic condition by establishing a sciatic nerve crushed injury model in mice and rats, and a hypoxia model in human umbilical vascular endothelial cells (HUVECs) in vitro. We found that SPRC accelerated the function recovery of the injured sciatic nerve and alleviated atrophy of the gastrocnemius muscle in mice. It facilitated the viability of Schwann cells (SCs), the outgrowth and myelination of regenerated axons, and angiogenesis in rats. It enhanced the viability, proliferation, adhesion, migration, and tube formation of HUVECs under hypoxic condition. SPRC activated sirtuin1 (SIRT1) expression by promoting the production of endogenous H2S, and SIRT1 negatively regulated Notch signaling in endothelial cells (ECs), thereby promoting angiogenesis. Collectively, our study has provided important evidence that SPRC has an effective role in peripheral nerve repair through microvascular reconstruction, which could be a potentially effective medical therapy for peripheral nerve injury.

Hirsutine ameliorates hepatic and cardiac insulin resistance in high-fat diet-induced diabetic mice and in vitro models.

Closely associated with type 2 diabetes mellitus (T2DM), hepatic steatosis and cardiac hypertrophy resulting from chronic excess intake can exacerbate insulin resistance (IR). The current study aims to investigate the pharmacological effects of hirsutine, one indole alkaloid isolated from Uncaria rhynchophylla, on improving hepatic and cardiac IR, and elucidate the underlying mechanism. T2DM and IR in vivo were established by high-fat diet (HFD) feeding for 3 months in C57BL/6 J mice. In vitro IR models were induced by high-glucose and high-insulin (HGHI) incubation in HepG2 and H9c2 cells. Hirsutine administration for 8 weeks improved HFD-induced peripheral hyperglycemia, glucose tolerance and IR by OGTT and ITT assays, and simultaneously attenuated hepatic steatosis and cardiac hypertrophy by pathological observation. The impaired p-Akt expression was activated by hirsutine in liver and heart tissues of HFD mice, and also in the models in vitro. Hirsutine exhibited the effects on enhancing glucose consumption and uptake in IR cell models via activating phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which was blocked by PI3K inhibitor LY294002. Moreover, the effect of hirsutine on promoting glucose uptake and GLUT4 expression in HGHI H9c2 cells was also prevented by Compound C, an inhibitor of AMP-activated protein kinase (AMPK). Enhancement of glycolysis might be another factor of hirsutine showing its effects on glycemic control. Collectively, it was uncovered that hirsutine might exert beneficial effects on regulating glucose homeostasis, thus improving hepatic and cardiac IR, and could be a promising compound for treating diet-induced T2DM.

Complete Genome Sequencing and Comparative Analysis of Citrobacter koseri CKNJ, a Strain Isolated from a Patient with Endogenous Endophthalmitis.

Citrobacter koseri (C. koseri) is an opportunistic pathogen that can cause a variety of diseases. Although the mortality rate of C. koseri infections is high, there is a paucity of clinical information. Furthermore, the genomic features of this species are poorly understood. Herein, we present a patient with endogenous endophthalmitis secondary to septicemia, and collected a C. koseri isolate, CKNJ, from the blood of the patient. Whole genome sequencing revealed that CKNJ harbors no plasmids and codes for 67 putative virulence factors. Whole genome single nucleotide polymorphism-based phylogenetic analysis revealed that the CKNJ strain was close to strains with the same isolation sites. Compared to the other sequenced C. koseri chromosomes, CKNJ contains several strain-variable regions, including one prophage and 2 large genomic islands. Sequencing of the first complete genome of a clinical strain from China should reinforce our understanding of the genomic features and pathogenicity of this invasive infection-causing C. koseri with clinical significance.

CCAAT/enhancer binding protein (C/EBP) delta promotes the expression of PTX3 and macrophage phagocytosis during A. fumigatus infection.

Given the increasing incidence of pulmonary aspergillosis, it is important to understand the natural defense mechanisms by which the body can kill Aspergillus fumigatus conidia. Pentraxin 3 (PTX3) plays a nonredundant role in resistance to A. fumigatus. Here, we found that the key predicted PTX3 transcription factor, CCAAT/enhancer-binding protein δ (CEBPD), was up-regulated during A. fumigatus conidia infection. Functionally, CEBPD significantly promoted the expression of PTX3 and the phagocytic ability of macrophages. Mechanistically, CEBPD activated the PTX3 by directly binding to the promoter region of the PTX3 gene. We also showed that the RNA-binding protein human antigen R promoted CEBPD expression. These findings provide new insights into the crucial role of CEBPD in the phagocytosis of A. fumigatus conidia by macrophages and highlight this protein as a potential therapeutic target for invasive pulmonary aspergillosis.

Continual Decline in Azole Susceptibility Rates in Candida tropicalis Over a 9-Year Period in China.

BACKGROUND: There have been reports of increasing azole resistance in Candida tropicalis, especially in the Asia-Pacific region. Here we report on the epidemiology and antifungal susceptibility of C. tropicalis causing invasive candidiasis in China, from a 9-year surveillance study. METHODS: From August 2009 to July 2018, C. tropicalis isolates (n = 3702) were collected from 87 hospitals across China. Species identification was carried out by mass spectrometry or rDNA sequencing. Antifungal susceptibility was determined by Clinical and Laboratory Standards Institute disk diffusion (CHIF-NET10-14, n = 1510) or Sensititre YeastOne (CHIF-NET15-18, n = 2192) methods. RESULTS: Overall, 22.2% (823/3702) of the isolates were resistant to fluconazole, with 90.4% (744/823) being cross-resistant to voriconazole. In addition, 16.9 (370/2192) and 71.7% (1572/2192) of the isolates were of non-wild-type phenotype to itraconazole and posaconazole, respectively. Over the 9 years of surveillance, the fluconazole resistance rate continued to increase, rising from 5.7 (7/122) to 31.8% (236/741), while that for voriconazole was almost the same, rising from 5.7 (7/122) to 29.1% (216/741), with no significant statistical differences across the geographic regions. However, significant difference in fluconazole resistance rate was noted between isolates cultured from blood (27.2%, 489/1799) and those from non-blood (17.6%, 334/1903) specimens (P-value < 0.05), and amongst isolates collected from medical wards (28.1%, 312/1110) versus intensive care units (19.6%, 214/1092) and surgical wards (17.9%, 194/1086) (Bonferroni adjusted P-value < 0.05). Although echinocandin resistance remained low (0.8%, 18/2192) during the surveillance period, it was observed in most administrative regions, and one-third (6/18) of these isolates were simultaneously resistant to fluconazole. CONCLUSION: The continual decrease in the rate of azole susceptibility among C. tropicalis strains has become a nationwide challenge in China, and the emergence of multi-drug resistance could pose further threats. These phenomena call for effective efforts in future interventions.

miR-212-5p exerts tumor promoter function by regulating the Id3/PI3K/Akt axis in lung adenocarcinoma cells.

microRNAs may function as oncogenes or tumor suppressor genes that play crucial roles in human carcinogenesis and cancer development. Growing evidence revealed that the tumor suppressor Id3 is involved in tumor progression, carcinogenesis, and the tumor microenvironment. We identified miR-212-5p as a negative posttranscriptional modulator of Id3. Dual luciferase reporter assay was used to verify that Id3 is a direct target gene of miR-212-5p. Id3 was lowly expressed and miR-212-5p was highly expressed in non-small-cell lung cancer (NSCLC) tissues and cells. In addition, we found that NSCLC patients having a higher level of miR-212-5p expression had a shorter survival time. Besides this, miR-212-5p could directly target Id3 and reduce its expression. miR-212-5p overexpression significantly accelerated cell proliferation, migration, and invasion by reversing the effects of Id3. Id3 overexpression by silencing miR-212-5p expression suppressed phosphatidylinositol 3 kinase (PI3K)/Akt activity and consequently promoted apoptosis and inhibited cell proliferation in lung cancer cells. Consistent with the in vitro results, a xenograft mouse model was used to validate the fact that miR-212-5p could promote tumorigenesis by targeting Id3 and activate the PI3K/Akt pathway in vivo as well. Taken together, the present results indicated that miR-212-5p may be involved in progression of NSCLC through the PI3K/Akt signaling pathway by targeting Id3.

Wetland ecosystem status and restoration using the Ecopath with Ecosim (EWE) model.

With increasing awareness of the importance of wetlands, the number of new or restored wetlands in China is steadily growing; however, not all of them fulfill their expected ecological function. Maintaining wetlands in their optimal state is an urgent problem that requires research into the ecosystem evaluation, regulation, and biomass management of wetlands. The Ecopath with Ecosim (EWE) model, also known as the ecological channel model, is a balance model that can directly construct the ecological system structure and describe its energy flow and mass transfer through the principle of nutrition dynamics. Here, the EWE model is applied to determine the ecosystem status of a newly restored wetland, Zhushanhu wetland, in the Lake Tai buffer zone of Zhushan Bay, and evaluate the current ecological regulations and biomass control measures. Our results provide theoretical and scientific support for the management and maintenance of wetland ecological restorations.

[Design of Smart Care Tele-Monitoring System for Mother and Fetus].

OBJECTIVE: To study and design a maternal and fetal monitoring system based on the cloud computing and internet of things, which can monitor and take smart care of the mother and fetus in 24 h. METHODS: Using a new kind of wireless fetal monitoring detector and a mobile phone, thus the doctor can keep touch with hospital through internet. The mobile terminal was developed on the Android system, which accepted the data of fetal heart rate and uterine contraction transmitted from the wireless detector, exchange information with the server and display the monitoring data and the doctor's advice in real-time. RESULTS: The mobile phone displayed the fetal heart rate line and uterine contraction line in real-time, recorded the fetus' grow process. It implemented the real-time communication between the doctor and the user, through wireless communication technology. CONCLUSIONS: The system removes the constraint of traditional telephone cable for users, while the users can get remote monitoring from the medical institutions at home or in the nearest community at any time, providing health and safety guarantee for mother and fetus.

Regulation of Neurotrophin-3 and Interleukin-1ß and Inhibition of Spinal Glial Activation Contribute to the Analgesic Effect of Electroacupuncture in Chronic Neuropathic Pain States of Rats.

Growing evidence indicates that neurotrophin-3, interleukin-1ß, and spinal glia are involved in neuropathic pain derived from dorsal root ganglia to spinal cord. Electroacupuncture is widely accepted to treat chronic pain, but the precise mechanism underlying the analgesic effect of EA has not been fully demonstrated. In this study, the mechanical withdrawal threshold and thermal withdrawal latency were recorded. We used immunofluorescence and western blots methods to investigate the effect of EA on the expression of NT-3 and IL-1ß in DRG and spinal cord of CCI rats; we also examined the expression of spinal GFAP and OX-42 in spinal cord. In present study, the MWT and TWL of CCI group rats were lower than those in the Sham CCI group rats, but EA treatment increased the pain thresholds. Furtherly, we found that EA upregulates the expression of NT-3 in DRG and spinal cord of CCI rats, while EA downregulates the expression of IL-1ß. Additionally, immunofluorescence exhibited that CCI-induced activation of microglia and astrocytes was inhibited significantly by EA treatment. These results demonstrated that the analgesic effect of EA may be achieved through promoting the neural protection of NT-3 as well as the inhibition of IL-1ß production and spinal glial activity.

Performance of mass spectrometric identification of bacteria and yeasts routinely isolated in a clinical microbiology laboratory using MALDI-TOF MS.

BACKGROUND: Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is an emerging technology newly applied to identifying bacterial and yeast strains. The aim of this study was to evaluate the clinical performance of the VITEK(®) MS system in the identification of bacteria and yeast strains routinely isolated from clinical samples. METHODS: We prospectively analyzed routine MALDI-TOF mass spectrometry identification in parallel with conventional phenotypic identification of bacteria and yeasts regardless of phylum or source of isolation. Discordant results were resolved with 16S rDNA or internal transcribed spacer (ITS) gene sequencing. Colonies (a single deposit on a MALDI disposable target without any prior extraction step) were analyzed using the VITEK(®) MS system. Peptide spectra acquired by the system were compared with the VITEK(®) MS IVD database Version 2.0, and the identification scores were recorded. RESULTS: Of the 1,181 isolates (1,061 bacterial isolates and 120 yeast isolates) analyzed, 99.5% were correctly identified by MALDI-TOF mass spectrometry; 95.7% identified to the species level, 3.6% identified to the genus level, and 0.3% identified within a range of species belonging to different genera. Conversely, 0.1% of isolates were misidentified and 0.4% were unidentified, partly because the species were not included in the database. Re-testing using a second deposit provided a successful identification for 0.5% of isolates unidentified with the first deposit. Our results show that the VITEK(®) MS system has exceptional performance in identifying bacteria and yeast by comparing acquired peptide spectra to those contained in its database. CONCLUSIONS: MALDI-TOF mass spectrometry is a rapid, accurate, and relatively inexpensive method for bacterial and yeast identification. Our results demonstrate that the VITEK(®) MS system is a fast and reliable technique, and has the potential to replace conventional phenotypic identification for most bacterial and yeast strains routinely isolated in clinical microbiology laboratories.

Molecular and DNA methylation analysis of Peg10 and Xist gene in sheep.

Peg10 is a maternally imprinted gene located in the imprinted domain of human chromosome 7q21 and mouse proximal chromosome 6. It is predominantly expressed in, and participates in the formation of, the placenta. Moreover, Peg10 is overexpressed in hepatocellular carcinoma, and is involved in hepatocarcinogenesis. The large noncoding RNA Xist has been shown to direct the female mammalian X chromatosome dosage compensation pathway. In the present study, we obtained partial cDNA sequences of sheep Peg10 and Xist. mRNA expression analysis in nine organs showed that they were universally expressed in two-day old lambs. The mRNA expression profile of Peg10 showed similar tissue specificity to pig, but was different compared with human and mouse. We concluded that the Peg10 mRNA expression profile was species specific. However, there was little difference in Xist expression between nine tissues of female lambs. Using bisulfite sequencing, we revealed that the first exon of Xist was either completely methylated or completely unmethylated, indicating that the newly obtained fragment of Xist was also differentially methylated in sheep as the DMR of Peg10. We did not find tissue specific DNA methylation of Xist, consistent with the Xist mRNA expression profile.

[Detection of Escherichia coli in wastewater based on enzyme immunoassay].

This research described the fast detection method based on ELISA for the E. coli in drain of wastewater treatment plants. The optimized conditions, such as reaction format (sandwich or direct), the concentration of HRP-E. coli conjugate, anti-HPR antibody and pretreatment of E. coli, were studied. Those results showed that the linear range of detection for E. coli was 10 CFU/ mL - 6 x 10(4) CFU/mL. This method shows the potential ability for the technics control of wastewater treatment plants. Comparing with conventional methods, it is a convenient and sensitive detection method with low cost.