Intertwined Wdr47-NTD dimer recognizes a basic-helical motif in Camsap proteins for proper central-pair microtubule formation.

Calmodulin-regulated spectrin-associated proteins (Camsaps) bind to the N-terminal domain of WD40-repeat 47 (Wdr47-NTD; featured with a LisH-CTLH motif) to properly generate axonemal central-pair microtubules (CP-MTs) for the planar beat pattern of mammalian motile multicilia. The underlying molecular mechanism, however, remains unclear. Here, we determine the structures of apo-Wdr47-NTD and Wdr47-NTD in complex with a characteristic Wdr47-binding region (WBR) from Camsap3. Wdr47-NTD forms an intertwined dimer with a special cross-over region (COR) in addition to the canonical LisH and globular α-helical core (GAC). The basic WBR peptide adopts an α-helical conformation and anchors to a tailored acidic pocket embedded in the COR. Mutations in this target-binding pocket disrupt the interaction between Wdr47-NTD and Camsap3. Impairing Wdr47-Camsap interactions markedly reduces rescue effects of Wdr47 on CP-MTs and ciliary beat of Wdr47-deficient ependymal cells. Thus, Wdr47-NTD functions by recognizing a specific basic helical motif in Camsap proteins via its non-canonical COR, a target-binding site in LisH-CTLH-containing domains.

Investigation of an outbreak of Burkholderia cepacia infection caused by drug contamination in a tertiary hospital in China.

BACKGROUND: Contamination of drugs used in minimally invasive treatment may to lead to infection outbreaks and catastrophic public health events that require prompt detection and control. Our aim was to investigate the outbreak of Burkholderia cepacia infection and its source in a tertiary care, general hospital in Beijing, China. METHODS: We investigated the outbreak of B cepacia infection from January 2017 to March 2018. The investigation included a detailed review of all cases, and field investigations. Environmental and product cultures were performed at the microbiology laboratory in the hospital. Isolates were evaluated for molecular relatedness using pulsed-field gel electrophoresis performed in an independent laboratory. RESULTS: In total, 9 patients were infected from November 2017 to March 2018, and all patients had undergone the following surgeries: transurethral resection of the prostate (n = 4), perineal prostate biopsy (n = 2), transurethral resection of bladder tumors (n = 2), and ureteroscopy (n = 1). B cepacia was isolated from the urine of 9 patients, blood of 2 patients, grilles used for puncturing, and 2 samples in 1 batch of analgesic gels. Pulsed-field gel electrophoresis confirmed that the isolates from the patients and gels were homologous. CONCLUSIONS: Our investigation revealed that the outbreak of B cepacia infection was caused by drug contamination.

Lactobacillus plantarum TW1-1 Alleviates Diethylhexylphthalate-Induced Testicular Damage in Mice by Modulating Gut Microbiota and Decreasing Inflammation.

Diethylhexylphthalate (DEHP), acting as an endocrine disruptor, disturbed reproductive health. Here, we evaluated the effects of Lactobacillus plantarum TW1-1 (L. plantarum TW1-1) on DEHP-induced testicular damage in adult male mice. Results showed that oral supplementation of L. plantarum TW1-1 significantly increased the serum testosterone concentration, enhanced the semen quality, and attenuated gonad development defects in DEHP-exposed mice. L. plantarum TW1-1 also alleviated DEHP-induced oxidative stress and inflammatory responses by decreasing the mRNA expression and serum protein concentration of different inflammatory factors [tumor necrosis factor-α, interleukin (IL)-1ß and IL-6]. Furthermore, L. plantarum TW1-1 significantly reduced DEHP-induced intestinal hyper-permeability and the increase in the serum lipopolysaccharide level. Gut microbiota diversity analysis revealed that L. plantarum TW1-1 shifted the DEHP-disrupted gut microbiota to that of the control mice. At phylum level, L. plantarum TW1-1 reversed DEHP-induced Bacteroidetes increase and Firmicutes decrease, and restored Deferribacteres in DEHP-exposed mice. Spearman's correlation analysis showed that Bacteroidetes, Deferribacteres, and Firmicutes were associated with DEHP-induced testicular damage. In addition, the ratio of Firmicutes to Bacteroidetes (Firm/Bac ratio) significantly decreased from 0.28 (control group) to 0.13 (DEHP-exposed group), which was restored by L. plantarum TW1-1 treatment. Correlation analysis showed that the Firm/Bac ratio was negatively correlated with testicular damage and inflammation. These findings suggest that L. plantarum TW1-1 prevents DEHP-induced testicular damage via modulating gut microbiota and decreasing inflammation.

[Role of dendritic cells in lipopolysaccharide induced cardiac dysfunction in mice].

OBJECTIVE: To observe the role of dendritic cells (DC) in lipopolysaccharide (LPS)-induced myocardial dysfunction in mice. METHODS: Eighty wild type male C57BL/6 mice were divided into four groups, according to random number table method: sham group, DC inhibitors in control group (VAG539-sham group), LPS sepsis model group (LPS group) and DC inhibitors pretreatment group (VAG539-LPS group), 20 in each group. The cardiac dysfunction model of sepsis mice was established by LPS intraperitoneal injection; the sham group was injected with the same dose of normal saline. VAG539-sham group and VAG539-LPS group were injected with the DC inhibitor VAG539 (30 mg/kg, twice per day, for 2 days) before injection with normal saline or LPS, respectively. Ten mice in each group were used to observe the 14-day survival rate. Mean arterial pressure (MAP) of the remaining 10 mice was measured through the small animal tail artery cannula; the cardiac function [including the heart rate (HR), left ventricular ejection fraction (LVEF) and short axial shortening rate (FS)] were evaluated by small animal echocardiography; the aggregation and maturation of myocardial DC were detected by flow cytometry; and serum inflammatory factors [including tumor necrosis factor-α (TNF-α), interleukins (IL-12, IL-6)] were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with sham group, the 14-day cumulative survival rate in LPS group was significantly reduced, while HR, MAP, LVEF and FS were significantly decreased, and the number of DC in myocardial tissues was significantly increased, and the levels of serum inflammatory factors were increased significantly. The 14-day cumulative survival rate in VAG539-LPS group was significantly higher than that in the LPS group (55% vs. 15%, P < 0.05). Compared with LPS group, after pretreatment by VAG539, the HR, MAP, LVEF and FS were significantly increased [HR (bpm): 610±25 vs. 556±28, MAP (mmHg, 1 mmHg = 0.133 kPa): 68±6 vs. 42±2, LVEF: 0.48±0.02 vs. 0.30±0.03, FS: (34±3)% vs. (14±2)%, P < 0.05]; the number of DC in myocardial tissue was significantly decreased from 6.5% to 3.7%; the level of serum inflammatory factors were significantly decreased [TNF-α (ng/L): 192.00±25.45 vs. 291.34±23.12, IL-12 (ng/L): 58.44±12.37 vs. 78.43±11.24, IL-6 (ng/L): 46.97±8.12 vs. 149.12±15.45, all P < 0.05]. CONCLUSIONS: Sepsis can cause cardiac dysfunction, and it can play an important role by inhibiting the DC cell function of myocardium and reducing the expression of inflammatory factors.

Impact of the Antibiotic Stewardship Program on Prevention and Control of Surgical Site Infection during Peri-Operative Clean Surgery.

BACKGROUND: Surgical site infections (SSIs) are the leading cause of hospital-acquired infections and are associated with substantial healthcare costs, with increased morbidity and mortality. To investigate the effects of the antibiotic stewardship program on prevention and control of SSI during clean surgery, we investigated this situation in our institution. PATIENTS AND METHODS: We performed a quasi-experimental study to compare the effect before and after the antibiotic stewardship program intervention. During the pre-intervention stage (January 1, 2010 through December 31, 2011), comprehensive surveillance was performed to determine the SSI baseline data. In the second stage (January 1, 2012 through December 31, 2016), an infectious diseases physician and an infection control practitioner identified the surgical patients daily and followed up on the duration of antimicrobial prophylaxis. RESULTS: From January 1, 2010 to December 31, 2016, 41,426 patients underwent clean surgeries in a grade III, class A hospital. The rate of prophylactic antibiotic use in the 41,426 clean surgeries was reduced from 82.9% to 28.0% after the interventions. The rate of antibiotic agents administered within 120 minutes of the first incision increased from 20.8% to 85.1%. The rate at which prophylactic antimicrobial agents were discontinued in the first 24 hours after surgery increased from 22.1% to 60.4%. Appropriate antibiotic selection increased from 37.0% to 93.6%. Prophylactic antibiotic re-dosing increased from 3.8% to 64.8%. The SSI rate decreased from 0.7% to 0.5% (p < 0.05). The pathogen detection rate increased from 16.7% up to 41.8% after intervention. The intensity of antibiotic consumption reduced from 74.9 defined daily doses (DDDs) per 100 bed-days to 34.2 DDDs per 100 bed-days after the interventions. CONCLUSION: Long-term and continuous antibiotic stewardship programs have important effects on the prevention and control of SSI during clean surgery.

Antidepressant activity of astilbin: involvement of monoaminergic neurotransmitters and BDNF signal pathway.

Depression and related mood disorders are among the world's greatest public health problems. Previous studies have demonstrated that astilbin (AST) has broad pharmacological functions which may modulate numerous pathways, such as antioxidant, scavenging free radicals, anti-inflammatory and so on, similarly to some of other flavonoids. In this study, the antidepressant-like effect of AST was investigated using chronic unpredictable mild stress (CUMS) model of depression in mice. The results showed that chronic administration of AST at doses of 10, 20 and 40 mg/kg (intraperitoneally (i.p.), 21 d) reduced depressive-like behaviors of mice in the forced swim test (FST), tail suspension test (TST) and sucrose preference test (SPT) without affecting locomotor activity. AST increased the contents of serotonin (5-HT) and dopamine (DA) in the frontal cortex of CUMS mice. Additionally, it was shown that AST treatment restored the CUMS-induced inhibition of extracellular signal-regulated kinase (ERK) 1/2 and AKT phosphorylation in the frontal cortex, conformed to the brain-derived neurotrophic factor (BDNF) expression. Our findings suggest that AST has antidepressant activities and the mechanisms, at least in part, relate to up-regulation of monoaminergic neurotransmitters (5-HT and DA) and activation of the BDNF signaling pathway.

Protocatechuic acid improves cognitive deficits and attenuates amyloid deposits, inflammatory response in aged AßPP/PS1 double transgenic mice.

Protocatechuic acid (PCA), a phenolic compound of Radix Salviae Miltiorrhizae (RSM), has been found to have a protective effect on improving cognitive deficits in STZ-induced AD rats. The present study aimed to evaluate the potential protection activity of PCA on improving cognitive deficits and attenuating Aß deposition and inflammatory responses in aged AßPP/PS1 double transgenic AD-model mice. The results of Morris water maze test showed that PCA (100mg/kg) significantly prolonged the mean latency time and the path length of AßPP/PS1 mice. PCA could significantly reduce the number of Aß positive expressions in the hippocampus and cerebral cortex of AßPP/PS1 mice by immunocytochemical assay with Congo red staining and decrease remarkably APP expression level by Western blot analysis (P<0.01). The results from ELISA and Western blot analysis showed that the levels of inflammatory cytokines including TNF-α, IL-1ß, IL-6 and IL-8 decreased remarkably by the treatment with PCA (P<0.01). Further, there was a substantial increase of brain derived neurotrophic factor (BDNF) in the hippocampus and cerebral cortex of AßPP/PS1 mice treated with PCA (P<0.01). The present study provided confirmatory evidence that PCA significantly decreased Aß deposits, APP and inflammatory response, whereas increased learning and memory ability, as well as enhanced BDNF level. Our findings indicated that PCA is an effective neuroprotective agent for AD therapy. It might be associated with the attenuation on Aß deposits and inflammation responses involved in the process.

Fitting characteristics of N95 filtering-facepiece respirators used widely in China.

BACKGROUND: Millions of people rely on N95 filtering facepiece respirators to reduce the risk of airborne particles and prevent them from respiratory infections. However, there are no respirator fit testing and training regulations in China. Meanwhile, no study has been conducted to investigate the fit of various respirators. The objective of this study was to investigate whether people obtained adequate fit when wearing N95 filtering facepiece respirators (FFRs) used widely in China. METHODS: Fifty adult participants selected using the Chinese respirator fit test panel donned 10 common models of N95 FFRs. Fit factors (FF) and inward leakage were measured using the TSI PortaCount Plus. Each subject was tested with three replications for each model. A subject was considered to pass the fit test when at least two of the three FFs were greater than 100. Two models were conducted fit tests before and after training to assess the role of training. RESULTS: The geometric mean FFs for each model and trained subjects ranged from <10 to 74.0. The fifth percentile FFs for only two individual respirator models were greater than 10 which is the expected level of performance for FFRs. The passing rates for these two models of FFRs were 44.7% and 20.0%. The passing rates were less than 10.0% for the other eight models. There were 27 (54%) participants who passed none of the 10 FFRs. The geometric mean FFs for both models when the subjects received training (49.7 and 74.0) were significantly larger than those when the same group of subjects did not receive any training (29.0 and 30.9) (P<0.05). CONCLUSIONS: FFRs used widely in China should be improved according to Chinese facial dimensions. Respirator users could benefit from respirator training and fit testing before using respirators.

An analysis of the current educational status and future training needs of China's rural doctors in 2011.

OBJECTIVES: To analyse the educational status and future training needs of China's rural doctors and provide a basis to improve their future training. METHODS: A cross-sectional epidemiological survey was used for the analysis, and 17 954 rural doctors chosen randomly from the eastern, central and western regions of China in 2009-2010 were surveyed to ascertain their average training time and the methods used for and content of their training. RESULTS: In general, 8671/17 778 (48.77%) of respondents received less than 12 days of training in a year. Conference sessions seemed to be the major route of training, with 10 150/17 925 respondents (56.62%). Clinical skills, with a response rate of 14 441/17 926 (80.56%), seemed to be the most popular training content. With regard to the general needs for training time received, 6547/18 255 (35.86%) of respondents hoped the average training time received a year would be less than 12 days; on-site guidance from a senior doctor was the most popular training method with response rate of 10 109/17 976 (56.24%), and clinical skills was what rural doctors wished to study the most, with a positive response of 16 744/17 962 (93.22%). Statistically significant differences existed in the current status and training time, training method and training content needs of China's rural doctors. CONCLUSIONS: Our results suggest that the training status and needs of China's rural doctors are still disjointed; measures including the introduction of remote education and clinical further education, extended training time and more clinical skills training should be adopted.

[Apoptosis induced by diacetyldianhydrogalactitol and its mechanism in HL-60 leukemia cells].

AIM: To investigate the apoptosis induced by diacetyldianhydrogalactitol (DADAG) and its mechanism in human HL-60 leukemia cells. METHODS: Inhibition of proliferation was measured by MTT assay. DADAG-induced apoptosis in HL-60 cells was observed by electron microscopy, flow cytometry and DNA fragmentation assay. The levels of Bcl-2 family proteins were detected by Western blotting. Caspase-3 activity was determined by ApoAlert CPP32 colorimetric assay kit. RESULTS: DADAG exhibited potent antiproliferative activity and induced apoptosis in HL-60 cells. After treatment with DADAG 8 micrograms.mL-1 for various times, the Bcl-XL protein level decreased in a time-dependent manner, while the Bad protein level was upregulated. The caspase-3 activity increased markedly after treatment with DADAG for 24 h. The apoptotic signals were suppressed by z-VAD.fmk (a general inhibitor of caspases), whereas z-DEVD.fmk, a selective inhibitor of caspase-3, only induced partial reversion of the apoptotic effects. CONCLUSION: DADAG-induced apoptosis in HL-60 cells required caspase-3 activation and caspase-3 activation was related with Bcl-2 family members.