Identification and pathogenicity of Fusarium spp. associated with tea wilt in Zhejiang Province, China.

BACKGROUND: Tea is one of the most widely consumed beverages in the world, with significant economic and cultural value. However, tea production faces many challenges due to various biotic and abiotic stresses, among which fungal diseases are particularly devastating. RESULTS: To understand the identity and pathogenicity of isolates recovered from tea plants with symptoms of wilt, phylogenetic analyses and pathogenicity assays were conducted. Isolates were characterized to the species level by sequencing the ITS, tef-1α, tub2 and rpb2 sequences and morphology. Four Fusarium species were identified: Fusarium fujikuroi, Fusarium solani, Fusarium oxysporum, and Fusarium concentricum. The pathogenicity of the Fusarium isolates was evaluated on 1-year-old tea plants, whereby F. fujikuroi OS3 and OS4 strains were found to be the most virulent on tea. CONCLUSIONS: To the best of our knowledge, this is the first report of tea rot caused by F. fujikuroi in the world. This provides the foundation for the identification and control of wilt disease in tea plants.

Defining disease progression in Chinese mainland people: Association between bone mineral density and knee osteoarthritis.

OBJECTIVE: To evaluate change in bone mineral density (BMD) during development of knee osteoarthritis (OA) in elderly Chinese community residents. Further, to monitor disease progression by recording speed of sound (SOS), one parameter of BMD provided by quantitative ultrasound measurement. METHODS: A total of 4173 community residents of the Chinese mainland were organized to complete questionnaires and relevant measurements, including anthropometry, radiology and quantitative ultrasound (QUS). SOS measurements of the distal radius were acquired using QUS measurements. The Kellgren-Lawrence (KL) grade of knee OA was evaluated by two experienced radiographers using X-rays. Finally, a general linear models analysis was performed to determine potential relationships. Further, the area under the receiver operating characteristic curve (ROC AUC) was applied to assess the distinction model. RESULTS: The SOS score in the OA group was significantly lower than that in the control group (p â€‹< â€‹0.001). However, after adjustment for age and body mass index (BMI), no significant difference was observed in the male population (p â€‹ï¼ â€‹0.841), while a significantly lower SOS score presented in knee OA participants in the female population (p â€‹ï¼ â€‹0.033). A turning point in SOS scores, from increasing to decreasing trends, occurred around KL grade 2; the SOS score gradually increased with progression in participants from KL grades 0 to 2, whereas the SOS score presented a significant decrease in participants with KL grades 3 and 4. The AUC for the model to distinguish OA progression was 0.891. CONCLUSION: There was a non-linear and stage-specific association between SOS score and knee OA, which presented a positive relationship in early stages, but a negative relationship in advanced stages. A decline of SOS score in knee OA patients in early stages should alert clinicians to the possibility of disease progression. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: In the present study, the relationship between OA and BMD had established by SOS. The results suggested that close monitoring of SOS in elderly Chinese communities residents with knee OA could alert disease progression involvement by an easily accessible method, and help early referral to orthopedist consultation for further examination and treatment.

The safety and tolerability of combined immune checkpoint inhibitors (anti-PD-1/PD-L1 plus anti-CTLA-4): a systematic review and meta-analysis.

BACKGROUND: The future of combined immunotherapy (a PD-1/PD-L1 plus a CTLA-4 antagonist) is very bright. However, besides improving efficacy, combined therapy increases treatment-related adverse events (TRAEs). Also, the clinical application is limited in some solid tumors. METHODS: This paper purports to investigate the TRAEs for the combined immunotherapy aiming for a more appropriate utilization of immune checkpoint inhibitors (ICIs) in clinical practice through a meta-analysis. RESULTS: A total of 17 eligible studies covering 2626 patients were selected for a meta-analysis based on specified inclusion and exclusion criteria. The incidence rates of any grade and grade 3 or higher TRAEs were 88% (95%CI, 84-92%) and 41% (95%CI, 35-47%), respectively. The overall incidence of any grade TRAEs leading to discontinuation of treatment was 20% (95%CI, 16-24%). The incidence rate of treatment related deaths was 4.3‰ (95%CI, 1.4‰-8.4‰). Analysis showed that NIVO1 + IPI3 cohort had higher incidences of grade 3 or higher TRAEs (RR = 1.77, 95%CI, 1.34-2.34, p < 0.0001) and any grade TRAEs leading to discontinuation of treatment (RR = 1.81, 95%CI, 1.08-3.04, P = 0.02), compared with NIVO3 + IPI1 regimen. CONCLUSIONS: The combined therapy had high TRAEs. The TRAEs, especially grade 3 or higher, led to discontinuation of the treatment. Furthermore, the incidence of treatment-related deaths was rare. Moreover, the NIVO3 + IPI1 regimen, regardless of efficacy, is more recommended because of better tolerance and lower adverse events.

A Risk-Scoring Model for Predicting Lymph Node Metastasis in Early Gastric Cancer Patients: a Retrospective Study and External Validation.

BACKGROUND: The possibility of lymph node metastasis (LNM) is critical to the assessment of the indication for endoscopic submucosal dissection. Thus, the aim of this study is to identify the risk factors for LNM and construct a risk-scoring model for patients with early gastric cancer to guide treatment. METHODS: A retrospective examination of reports and studies carried out January 2000 and December 2014 was conducted. A risk-scoring model for predicting LNM was developed based on the data thus collected. In addition, the model is subject to verification and validation by three institutions. RESULTS: Of the 1029 patients, 228 patients (22%) had LNM. Multivariate analysis showed that female, depressed type, undifferentiated type, submucosa, tumor size, and lymphovascular invasion were significantly associated with LNM. An 11-point risk-scoring model was used to predict LNM risk. An area under the receiver operating characteristic (AUROC) of the risk-scoring model was plotted using the development set and the AUROC of the model [0.76 (95% CI 0.73-0.80)] to predict LNM risk. After internal and external validation, the AUROC curve for predicting LNM was 0.77 (95% CI 0.68-0.86), 0.82 (95% CI 0.72-0.91), and 0.82 (95% CI 0.70-0.94), respectively. CONCLUSIONS: A risk-scoring model for predicting LNM was developed and validated. It could help with personalized care for patients with EGC.

Central IKK2 Inhibition Ameliorates Air Pollution-Mediated Hepatic Glucose and Lipid Metabolism Dysfunction in Mice With Type II Diabetes.

Previous studies supported a role of hypothalamic inflammation in fine ambient particulate matter (PM2.5) exposure-mediated diabetes development. We therefore investigated the effects of PM2.5 exposure on insulin resistance and the disorders of hepatic glucose and lipid metabolism via hypothalamic inflammation. KKAy mice, a genetically susceptible model of type II diabetes mellitus, were administered intra-cerebroventricularly with IKK2 inhibitor (IMD-0354) and were exposed to either concentrated PM2.5 or filtered air (FA) for 4 weeks simultaneously via a versatile aerosol concentration exposure system. At the end of the exposure, fasting blood glucose and serum insulin were evaluated before epididymal adipose tissue and liver were collected, flow cytometry, quantitative PCR and Western blot were performed at euthanasia. We observed that intracerebroventricular administration of IMD-0354 attenuated insulin resistance, inhibited macrophage polarization to M1 phenotype in epididymal adipose tissue in response to PM2.5 exposure. Although the treatment did not affect hepatic inflammation or endoplasmic reticulum stress, it inhibited the expression of the enzymes for gluconeogenesis and lipogenesis in the liver. Therefore, our current finding indicates an important role of hypothalamic inflammation in PM2.5 exposure-mediated hepatic glucose and lipid metabolism disorder.

Particulate Air pollution mediated effects on insulin resistance in mice are independent of CCR2.

BACKGROUND: Chronic exposure to fine ambient particulate matter (PM2.5) induces insulin resistance. CC-chemokine receptor 2 (CCR2) appears to be essential in diet-induced insulin resistance implicating an important role for systemic cellular inflammation in the process. We have previously suggested that CCR2 is important in PM2.5 exposure-mediated inflammation leading to insulin resistance under high fat diet situation. The present study assessed the importance of CCR2 in PM2.5 exposure-induced insulin resistance in the context of normal diet. METHODS AND RESULTS: C57BL/6 and CCR2-/- mice were subjected to exposure to concentrated ambient PM2.5 or filtered air for 6 months. In C57BL/6 mice, concentrated ambient PM2.5 exposure induced whole-body insulin resistance, macrophage infiltration into the adipose tissue, and upregulation of phosphoenolpyruvate carboxykinase (PEPCK) in the liver. While CCR2 deficiency reduced adipose macrophage content in the PM2.5-exposed animals, it did not improve systemic insulin resistance. This lack of improvement in insulin resistance was paralleled by increased hepatic expression of genes in PEPCK and inflammation. CONCLUSION: CCR2 deletion failed to attenuate PM2.5 exposure-induced insulin resistance in mice fed on normal diet. The present study indicates that PM2.5 may dysregulate glucose metabolism directly without exerting proinflammatory effects.

Noise exposure in occupational setting associated with elevated blood pressure in China.

BACKGROUND: Hypertension is the primary out-auditory adverse outcome caused due to occupational noise exposure. This study investigated the associations of noise exposure in an occupational setting with blood pressure and risk of hypertension. METHODS: A total of 1,390 occupational noise-exposed workers and 1399 frequency matched non-noise-exposed subjects were recruited from a cross-sectional survey of occupational noise-exposed and the general population, respectively. Blood pressure was measured using a mercury sphygmomanometer following a standard protocol. Multiple logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) of noise exposure adjusted by potential confounders. RESULTS: Noise-exposed subjects had significantly higher levels of systolic blood pressure(SBP) (125.1 ± 13.9 mm Hg) and diastolic blood pressure (DBP) (77.6 ± 10.7 mm Hg) than control subjects (SBP: 117.2 ± 15.7 mm Hg, DBP: 70.0 ± 10.5 mm Hg) (P < 0.001). Significant correlations were found between noise exposure and blood pressure (SBP and DBP) (P < 0.001). However, the linear regression coefficients with DBP appeared larger than those with SBP. The prevalence of hypertension was 17.8% in subjects with noise exposure and 9.0% in control group (P < 0.001). Compared with the control group, the subjects with noise exposure had the risk of hypertension with an OR of 1.941 (95% CI = 1.471- 2.561) after adjusting for age, sex, smoking, and drinking status. Dose-response relationships were found between noise intensity, years of noise exposure, cumulative noise exposure and the risk of hypertension (all P values < 0.05). No significant difference was found between subjects wearing an earplug and those not wearing an earplug, and between steady and unsteady noise categories (P > 0.05). CONCLUSIONS: Occupational noise exposure was associated with higher levels of SBP, DBP, and the risk of hypertension. These findings indicate that effective and feasible measures should be implemented to reduce the risk of hypertension caused by occupational noise exposure.

Paraspeckle protein 1 (PSPC1) is involved in the cisplatin induced DNA damage response--role in G1/S checkpoint.

Paraspeckle protein 1 (PSPC1) was first identified as a structural protein of the subnuclear structure termed paraspeckle. However, the exact physiological functions of PSPC1 are still largely unknown. Previously, using a proteomic approach, we have shown that exposure to cisplatin can induce PSPC1 expression in HeLa cells, indicating the possible involvement for PSPC1 in the DNA damage response (DDR). In the current study, the role of PSPC1 in DDR was examined. First, it was found that cisplatin treatment could indeed induce the expression of PSPC1 protein. Abolishing PSPC1 expression by siRNA significantly inhibited cell growth, caused spontaneous cell death, and increased DNA damage. However, PSPC1 did not co-localize with γH2AX, 53BP1, or Rad51, indicating no direct involvement in DNA repair pathways mediated by these molecules. Interestingly, knockdown of PSPC1 disrupted the normal cell cycle distribution, with more cells entering the G2/M phase. Furthermore, while cisplatin induced G1/S arrest in HeLa cells, knockdown of PSPC1 caused cells to escape the G1/S checkpoint and enter mitosis, and resulted in more cell death. Taken together, these observations indicate a new role for PSPC1 in maintaining genome integrity during the DDR, particularly in the G1/S checkpoint.