Exploration of microbiome diversity of stacked fermented grains by flow cytometry and cell sorting.

Sauce-flavor baijiu is one of the twelve flavor types of Chinese distilled fermented product. Microbial composition plays a key role in the stacked fermentation of Baijiu, which uses grains as raw materials and produces flavor compounds, however, the active microbial community and its relationship remain unclear. Here, we investigated the total and active microbial communities of stacked fermented grains of sauce-flavored Baijiu using flow cytometry and high-throughput sequencing technology, respectively. By using traditional high-throughput sequencing technology, a total of 24 bacterial and 14 fungal genera were identified as the core microbiota, the core bacteria were Lactobacillus (0.08-39.05%), Acetobacter (0.25-81.92%), Weissella (0.03-29.61%), etc. The core fungi were Issatchenkia (23.11-98.21%), Monascus (0.02-26.36%), Pichia (0.33-37.56%), etc. In contrast, using flow cytometry combined with high-throughput sequencing, the active dominant bacterial genera after cell sorting were found to be Herbaspirillum, Chitinophaga, Ralstonia, Phenylobacterium, Mucilaginibacter, and Bradyrhizobium, etc., whereas the active dominant fungal genera detected were Aspergillus, Pichia, Exophiala, Candelabrochaete, Italiomyces, and Papiliotrema, etc. These results indicate that although the abundance of Acetobacter, Monascus, and Issatchenkia was high after stacked fermentation, they may have little biological activity. Flow cytometry and cell sorting techniques have been used in the study of beer and wine, but exploring the microbiome in such a complex environment as Chinese baijiu has not been reported. The results also reveal that flow cytometry and cell sorting are convenient methods for rapidly monitoring complex microbial flora and can assist in exploring complex environmental samples.

Survey report on keratoplasty in China: A 5-year review from 2014 to 2018.

To provide the general information on corneal transplantation (CT) in China, China Cornea Society designed a questionnaire on CT from 2014 to 2018 and entrusted it to 31 committee members for implementation of the survey nationwide. This article presents the results of the survey and compares the indicators used in the survey and those in the annual statistical report released by the Eye Bank Association of America (EBAA). The number of corneal transplantations completed by the 64 hospitals from 2014 to 2018 was respectively 5377, 6394, 7595, 8270 and 8980, totally 36,616 (22,959 male and 13,657 female). The five largest hospitals by the number of corneal transplantations completed 15,994 surgeries in total, accounting for 43.68% of all the surgeries performed in the 64 hospitals. The most common indication for corneal transplantations was corneal leukoma (7683, 20.98%), followed by bacterial keratitis (4209, 11.49%), corneal dystrophies (4189, 11.44%), keratoconus (3578, 9.77%) and corneal perforation (2839, 7.75%). The main surgical techniques were penetrating keratoplasty (PK) (19,896, 54.34%), anterior lamellar keratoplasty (ALK) (13,869, 37.88%). The proportion of PK decreased from 57.97% in 2014 to 52.88% in 2018 while the proportion of ALK increased from 36.04% in 2014 to 37.92% in 2018. The geographical distribution of keratoplasties performed in China is unbalanced. PK and ALK were the main techniques of CT and corneal leukoma, bacterial keratitis and corneal dystrophies were the main indications for CT in China.

Evaluation of the efficacy of optimal pulsed technology treatment in patients with cataract and Meibomian gland dysfunction in the perioperative period.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of M22 Optimal Pulsed Technology (OPT) applied in patients with age-related cataract and Meibomian gland dysfunction (MGD) in perioperative period. METHODS: This prospective observational study was carried out in the Jinan Mingshui Eye Hospital (Zhangqiu, China). We studied 60 patients (30 in the OPT treatment group and 30 in the conventional surgery group) with age-related cataract and MGD who underwent phacoemulsification and evaluated the efficacy of OPT treatment before and 1 month and 3 months after surgery. Ocular Surface Disease Index (OSDI) questionnaire, biomicroscopic examination of lid margins, Meibomian gland yielding secretion score (MGYSS), corneal fluorescein staining scores (CFS), tear film break-up time (TBUT), tear meniscus height (TMH) and the morphology of the MG (meibography) followed by Keratograph 5 M (K5M) were used to assess the patients' conditions. RESULTS: There were significant differences in the scores of OSDI, MGYSS, TBUT, and CFS between the preoperative and postoperative outcomes (p < 0.05). In the OPT treatment group, the postoperative ocular surface condition was obviously better and the patient satisfaction rate was higher than those before surgery. There were significant differences in the scores of OSDI, EMAS, MGYSS and CFS before and 1 month after surgery (p < 0.05). In addition, there were also significant differences in the scores of OSDI, EMAS, MGYSS and MGLS before and 3 months after surgery (p < 0.05). No complications appeared during OPT treatment. CONCLUSIONS: Cataract surgery can aggravate MGD and is detrimental to ocular surface health. OPT treatment was a safe and effective intervention for patients with MGD and cataract during perioperative period.

Synthesis of 4-Methoxy-1, 3-Benzenediolylhydrazones and Evaluation of Their Anti-Platelet Aggregation Activity.

In our present investigation, a series of novel 4-methoxy-1,3-benzenediolyl-hydrazones were designed and synthesized, and their ability to inhibit platelet aggregation was evaluated by adenosine diphosphate (ADP) and arachidonic acid (AA). The structures of the synthesized compounds were confirmed by spectral data. Results demonstrated that the activities of all compounds excelled the positive drug Picotamide (25.1% inhibition rate) and seven compounds (PNN01, PNN03, PNN05, PNN07, PNN09, PNN12, and PNN14) have efficiently inhibited platelet aggregation even higher than Clopidogrel (37.6% inhibition rate) induced by AA. Among them, PNN07 (39.8% inhibition rate) was considered as the most potent analogue. Evaluation of cytotoxic activity of the compounds against L929 cell line revealed that none of the compounds have significant cytotoxicity. Thus, diolylhydrazones derives are potential to be antiplatelet aggregation inhibitors and maybe working in AA-induced selectively.

Protective effects of low-intensity pulsed ultrasound on aluminum overload-induced cerebral damage through epigenetic regulation of brain-derived neurotrophic factor expression.

In consideration of its noninvasive administration and endogenous stimulation property, the enhancement of brain-derived neurotrophic factor (BDNF) via low-intensity pulsed ultrasound (LIPUS) could be a novel strategy for aluminum (Al) overload-induced cerebral damage. LIPUS was pre-treated 7 days before concomitantly given with aluminum chloride (AlCl3) daily for a period of 42 days. Morris water maze and elevated plus maze were performed to analyze spatial learning and memory. Western Blot and immunoprecipitation were used to detect BDNF and histone acetylation of histone H3 lysine 9 (H3K9) and histone H4 lysine 12 (H4K12) in the hippocampus. Assay of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) indicated the extent of oxidative damages. Aluminium exposure in rats can cause attenuated spatial learning and memory, followed by up-regulated histone deacetylase 6 (HDAC6) expression, down-regulated H3K9 and H4K12 acetylation at the PIII and PIV promoter of BDNF, all of which will eventually inhibit BDNF expression. LIPUS can recover reduced cognitive function by restoring histone acetylation and BDNF expression, accompanied with increased SOD, GSH, and GSH-Px activity. LIPUS treatment might alleviate aluminium exposure-induced cognitive decline by acetylation regulation of BDNF expression and reducing oxidative stress in the hippocampus.

Continuous and discontinuous transitions to synchronization.

We describe how the transition to synchronization in a system of globally coupled Stuart-Landau oscillators changes from continuous to discontinuous when the nature of the coupling is moved from diffusive to reactive. We explain this drastic qualitative change as resulting from the co-existence of a particular synchronized macrostate together with the trivial incoherent macrostate, in a range of parameter values for which the latter is linearly stable. In contrast to the paradigmatic Kuramoto model, this particular state observed at the synchronization transition contains a finite, non-vanishing number of synchronized oscillators, which results in a discontinuous transition. We consider successively two situations where either a fully synchronized state or a partially synchronized state exists at the transition. Thermodynamic limit and finite size effects are briefly discussed, as well as connections with recently observed discontinuous transitions.

Non-periodic outbreaks of recurrent epidemics and its network modelling.

The study of recurrent epidemic outbreaks has been attracting great attention for decades, but its underlying mechanism is still under debate. Based on a large number of real data from different cities, we find that besides the seasonal periodic outbreaks of influenza, there are also non-periodic outbreaks, i.e. non-seasonal or non-annual behaviors. To understand how the non-periodicity shows up, we present a network model of SIRS epidemic with both time-dependent infection rate and a small possibility of persistent epidemic seeds, representing the influences from the larger annual variation of environment and the infection generated spontaneously in nature, respectively. Our numerical simulations reveal that the model can reproduce the non-periodic outbreaks of recurrent epidemics with the main features of real influenza data. Further, we find that the recurrent outbreaks of epidemic depend not only on the infection rate but also on the density of susceptible agents, indicating that they are both the necessary conditions for the recurrent epidemic patterns with non-periodicity. A theoretical analysis based on Markov dynamics is presented to explain the numerical results. This finding may be of significance to the control of recurrent epidemics.

Renal blood perfusion in GK rats using targeted contrast enhanced ultrasonography.

OBJECTIVE: To explore application of targeted contrast enhanced ultrasonography in diagnosis of early stage vascular endothelial injury and diabetic nephropathy. METHODS: Targeted SonoVue-TM microbubble was prepared by attaching anti-TM monoclonal antibody to the surface of ordinary microbubble SonoVue by biotin - avidin bridge method and ultrasonic instrument was used to evaluate the developing situation of targeted microbubble in vitro. Twenty 12-week-old male GK rats and 20 Wistar rats were enrolled in this study, and were randomly divided into targeted angiography group and ordinary angiography group. Targeted microbubbles SonoVue-TM or general microbubble SonoVue were rapidly injected to the rats via tail vein; the developing situation of the two contrast agents in rats kidneys was dynamically observed. Time-intensity curve was used to analyze rat kidney perfusion characteristics in different groups. RESULTS: Targeted ultrasound microbubble SonoVue-TM was successfully constructed, and it could be used to develop an external image. Targeted microbubbles SonoVue-TM enabled clear development of experimental rat kidney. Time-intensity curve shapes of rat kidney of the two groups showed as single apex with steep ascending and slowly descending branch. Compared with the control group, the rising slope of the GK rat renal cortex, medulla in targeted angiography group increased (P < 0.05); the peak intensity of medulla increased (P < 0.05), and the total area under the curve of medulla increased (P < 0.05). Compared with control group, the ascending branch of the GK rat in renal cortex, medulla in ordinary angiography group increased (P < 0.05). The peak intensity of the curve increased (P < 0.05), and the total area under the curve increased (P < 0.05). Compared with the ordinary angiography group, the peak of GK rat medulla curve in targeted angiography group intensity increased (P < 0.05), and the total area under the curve increased (P < 0.05). CONCLUSIONS: Targeted microbubbles SonoVue-TM can make a clear development of experimental rat kidney, its stable performance meet the requirement of ultrasonic observation time limit, and it can reflect early changes of blood perfusion in GK rat kindey.

Integrated travel network model for studying epidemics: Interplay between journeys and epidemic.

The ease of travelling between cities has contributed much to globalization. Yet, it poses a threat on epidemic outbreaks. It is of great importance for network science and health control to understand the impact of frequent journeys on epidemics. We stress that a new framework of modelling that takes a traveller's viewpoint is needed. Such integrated travel network (ITN) model should incorporate the diversity among links as dictated by the distances between cities and different speeds of different modes of transportation, diversity among nodes as dictated by the population and the ease of travelling due to infrastructures and economic development of a city, and round-trip journeys to targeted destinations via the paths of shortest travel times typical of human journeys. An example is constructed for 116 cities in China with populations over one million that are connected by high-speed train services and highways. Epidemic spread on the constructed network is studied. It is revealed both numerically and theoretically that the traveling speed and frequency are important factors of epidemic spreading. Depending on the infection rate, increasing the traveling speed would result in either an enhanced or suppressed epidemic, while increasing the traveling frequency enhances the epidemic spreading.

A simplified memory network model based on pattern formations.

Many experiments have evidenced the transition with different time scales from short-term memory (STM) to long-term memory (LTM) in mammalian brains, while its theoretical understanding is still under debate. To understand its underlying mechanism, it has recently been shown that it is possible to have a long-period rhythmic synchronous firing in a scale-free network, provided the existence of both the high-degree hubs and the loops formed by low-degree nodes. We here present a simplified memory network model to show that the self-sustained synchronous firing can be observed even without these two necessary conditions. This simplified network consists of two loops of coupled excitable neurons with different synaptic conductance and with one node being the sensory neuron to receive an external stimulus signal. This model can be further used to show how the diversity of firing patterns can be selectively formed by varying the signal frequency, duration of the stimulus and network topology, which corresponds to the patterns of STM and LTM with different time scales. A theoretical analysis is presented to explain the underlying mechanism of firing patterns.

Contrast-enhanced ultrasonography is a valid technique for the assessment of renal microvascular perfusion dysfunction in diabetic Goto-Kakizaki rats.

AIM: To evaluate the reliability of contrast-enhanced ultrasonography (CEUS) for the detection of renal microvascular blood perfusion in a type 2 diabetic Goto-Kakizaki (GK) rat model. METHODS: Male GK and Wistar rats at the age of 4, 12 and 20 weeks (n=10, respectively) were used for the study. Real-time and haemodynamic imaging of the renal cortex was performed using CEUS with SonoVue. Outage time-intensity curves (TICs) were applied for the analysis of basic intensity, slope rates of the ascending (S1) and descending curves (S2), time to peak (TTP), half time of peak descending (HDT), peak intensity (PI), and total area under the curve (AUC). Immunohistochemical staining for endothelial cells (ECs) was performed using the CD34 monoclonal antibody for the quantification of microvessel density and distribution. RESULTS: Images of the renal cortex microvascular beds after injection of SonoVue in the rats were rapidly and clearly displayed, and it is easy to differentiate the enhanced and faded images of renal perfusion. The TICs of the GK rats were much wider than the controls; however, no significant changes in PI were found in all aged rats. Ultrasonographic quantitative analysis revealed a decrease in S1 and S2, and an increase in TTP, HDT and AUC in the 12- and 20-week-old GK rats compared with the controls (P<0.05). Moreover, the 20-week-old GK rats had much lower glomerular density and smaller distribution area of CD34-positive ECs, which was in parallel with more severe proteinuria, GBM thickening, glomerulosclerosis and interstitial vascular damages (P<0.05). Interestingly, negative correlations between AUC and glomerular microvessel density or distribution were detected, respectively (P<0.05). CONCLUSIONS: Contrast-enhanced ultrasonography is a valid technique for the real-time and dynamic assessment of renal cortex microvascular perfusion and haemodynamic characterization in GK rats.

Contrast-enhanced ultrasound with SonoVue could accurately assess the renal microvascular perfusion in diabetic kidney damage.

OBJECTIVE: The aim of this study was to investigate the clinical significance of real-time gray-scale contrast-enhanced ultrasound (CEUS) through evaluating renal microvascular perfusion in diabetic kidney damage. METHODS: Diabetic patients (aged: 62.5±7.2, n=33) were divided into Group A with chronic kidney disease (CKD) Stages I and II (n=19) and Group B (n=14) with CKD Stages IV and V. Twenty-one healthy adults were selected as control group. The real-time and dynamic imaging from renal cortex was performed using contrast-enhanced ultrasound with SonoVue. The outage time-intensity curves (TICs) with >85% goodness-of-fit index were chosen for the analysis of basic intensity, intensity increment (A1), arriving time (AT), time to peak (TTP), mean transit time, peak intensity (PI) and total area under the curve (AUC). RESULTS: (i) After intravenous injection of a contrast agent, the renal artery, cortex, pyramid and renal vein were clearly displayed in sequence. (ii) TIC of renal cortical Perfusion in all groups showed an asymmetrical single-peak curve, which has an obvious ascending slope, peak and descending slope. The ascending slope was steep, whereas the descending slope was flat. However, the ascending slope in Group A and B was flatter than that in the control group. (iii) Compared to the control group, AT and TTP were all markedly prolonged but A1 and PI were significantly decreased in Group A and B (P<0.05). In Group A, the AUC had a trend of increase; however, the area under the ascending slope (AUC1), area under the descending slope (AUC2) and AUC were all decreased in Group B (P<0.05). (iv) AUC positively correlated with glomerular filtration rate (GFR) (r=0.472, P=0.01), but TTP did not correlate well with GFR (r=0.262, P=0.177). CONCLUSIONS: CEUS could accurately assess renal microvascular perfusion in a real-time and dynamic manner. PI, TTP and AUC could be used for the diagnosis of the renal microvascular damage in early and late stage diabetic patients. CEUS is a safe, noninvasive and simple technique to detect the severity of kidney microvascular perfusion deficits.