[Spatial and temporal distribution characteristics of seasonal A(H3N2) influenza in China, 2014-2019].

Objective: To analyze the spatial and temporal distribution characteristics of seasonal A(H3N2) influenza [influenza A(H3N2)] in China and to provide a reference for scientific prevention and control. Methods: The influenza A(H3N2) surveillance data in 2014-2019 was derived from China Influenza Surveillance Information System. A line chart described the epidemic trend analyzed and plotted. Spatial autocorrelation analysis was conducted using ArcGIS 10.7, and spatiotemporal scanning analysis was conducted using SaTScan 10.1. Results: A total of 2 603 209 influenza-like case sample specimens were detected from March 31, 2014, to March 31, 2019, and the influenza A(H3N2) positive rate was 5.96%(155 259/2 603 209). The positive rate of influenza A(H3N2) was statistically significant in the north and southern provinces in each surveillance year (all P<0.05). The high incidence seasons of influenza A (H3N2) were in winter in northern provinces and summer or winter in southern provinces. Influenza A (H3N2) clustered in 31 provinces in 2014-2015 and 2016-2017. High-high clusters were distributed in eight provinces, including Beijing, Tianjin, Hebei, Shandong, Shanxi, Henan, Shaanxi, and Ningxia Hui Autonomous Region in 2014-2015, and high-high clusters were distributed in five provinces including Shanxi, Shandong, Henan, Anhui, and Shanghai in 2016-2017. Spatiotemporal scanning analysis from 2014 to 2019 showed that Shandong and its surrounding twelve provinces clustered from November 2016 to February 2017 (RR=3.59, LLR=9 875.74, P<0.001). Conclusion: Influenza A (H3N2) has high incidence seasons with northern provinces in winter and southern provinces in summer or winter and obvious spatial and temporal clustering characteristics in China from 2014-2019.

[Association between urinary arsenic level and serum testosterone in Chinese men aged 18 to 79 years].

Objective: To investigate the association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years. Methods: A total of 5 048 male participants aged 18 to 79 years were recruited from the China National Human Biomonitoring (CNHBM) from 2017 to 2018. Questionnaires and physical examinations were used to collect information on demographic characteristics, lifestyle, food intake frequency and health status. Venous blood and urine samples were collected to detect the level of serum total testosterone, urinary arsenic and urinary creatinine. Participants were divided into three groups (low, middle, and high) based on the tertiles of creatinine-adjusted urinary arsenic concentration. Weighted multiple linear regression was fitted to analyze the association of urinary arsenic with serum total testosterone. Results: The weighted average age of 5 048 Chinese men was (46.72±0.40) years. Geometric mean concentration (95%CI) of urinary arsenic, creatinine-adjusted urinary arsenic and serum testosterone was 22.46 (20.08, 25.12) µg/L, 19.36 (16.92, 22.15) µg/g·Cr and 18.13 (17.42, 18.85) nmol/L, respectively. After controlling for covariates, compared with the low-level urinary arsenic group, the testosterone level of the participants in the middle-level group and the high-level group decreased gradually. The percentile ratio (95%CI) was -5.17% (-13.14%, 3.54%) and -10.33% (-15.68%, -4.63). The subgroup analysis showed that the association between the urinary arsenic level and testosterone level was more obvious in the group with BMI<24 kg/m2 group (Pinteraction=0.023). Conclusion: There is a negative association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years.

Fermented rape pollen powder can alleviate benign prostatic hyperplasia in rats by reducing hormone content and changing gut microbiota.

Benign prostatic hyperplasia (BPH) can cause urethral compression, bladder stone formation, and renal function damage, which may endanger the life of patients. Therefore, we aimed to develop plant-based preparations for BPH treatment with no side effects. In this study, the Lactiplantibacillus plantarum 322Hp, Lactobacillus acidophilus 322Ha, and Limosilactobacillus reuteri 322Hr were used to ferment rape pollen. The fermented rape pollen was subsequently converted into fermented rape pollen powder (FRPP) through vacuum freeze-drying technology. After fermenting and drying, the bioactive substances and antioxidant capacity of FRPP were significantly higher than those of unfermented rapeseed pollen, and FRPP had a longer storage duration, which can be stored for over one year. To investigate the therapeutic effect of FRPP on BPH, a BPH rat model was established by hypodermic injection of testosterone propionate. The BPH rats were treated differently, with the model group receiving normal saline, the positive control group receiving finasteride, and the low, medium, and high dose FRPP group receiving FRPP at doses of 0.14 g/kg/d, 0.28 g/kg/d, and 0.56 g/kg/d, respectively. The results indicate that medium dose FRPP reduced the levels of hormone such as testosterone, dihydrotestosterone, and oestradiol in rats with BPH by about 32%, thus bringing the prostate tissue of BPH rats closer to normal. More importantly, medium dose FRPP treatment had a significant effect on the composition of gut microbiota in rats with BPH, increasing the levels of beneficial genera (such as Coprococcus and Jeotgalicoccus), and decreasing the levels of harmful pathogens (such as Turicibacter and Clostridiaceae_Clostridium) in the gut. This study showed that medium dose FRPP reduced the hormone level and regulated the unbalanced gut microbiota in BPH rats, thereby alleviating BPH.

The adaptation to freezing tolerance of hydrated lettuce seeds: effects of regional climate and of seed characteristics.

BACKGROUND: With global warming, soil seed banks at high altitudes face dual challenges, excessive water absorption and thinner snow cover that increase underground temperature. A better understanding of freezing tolerance of hydrated seeds provides insights for conservation in natural soil seed banks. OBJECTIVE: To understand the adaptation mechanisms of seed freezing tolerance under various climates, in relation to cooling rate and seed size. MATERIALS AND METHODS: Twelve ecotypes of lettuce (Lactuca sativa) seeds were collected from different geographical locations around the world. Seeds were fully hydrated and tested for their freezing tolerance using programmed cooling methods. RESULTS: The size of seeds from different climate regions varied, and was correlated with the freezing tolerance of the hydrated seeds (P < 0.05). Larger seeds showed poorer freezing tolerance. The local climates of maternal plants were also well correlated to seed freezing tolerance (P < 0.05), especially under slow cooling conditions. The seeds collected in regions with high spring rainfall exhibited greater freezing tolerance. CONCLUSION: Freezing tolerance of hydrated seeds is affected by the climate of maternal plants and by seed size. Our data revealed the existence of an adaptation mechanism of freezing tolerance among various ecotypes of lettuce seeds. doi.org/10.54680/fr22410110412.

[Effect of serum potassium level on renal function progression in stage â ¢-â ¤ chronic kidney disease patients without dialysis].

Objective: To investigate the effect of serum potassium level and hyperkalemia on the renal function decline in chronic kidney disease (CKD) patients. Methods: The clinical data at baseline and follow-up in stage Ⅲ-Ⅴ CKD patients without dialysis who were followed up for more than one year in Tianjin First Central Hospital from May 2015 to June 2019 and Teikyo University School of Medicine from January 2008 to July 2013 were retrospectively collected. All patients were divided into stable group (337 cases), slow progression group (337 cases) and rapid progression group (338 cases) according to the tertile of estimated glomerular filtration rate (eGFR) slope (the annual average percentage of eGFR decline). Multivariate logistic regression analysis models were used to evaluate the correlations of baseline serum potassium or time-averaged serum potassium level with CKD rapid progression. Results: Three hundred and forty-three cases from Tianjin First Central Hospital and 669 cases from Teikyo University School of Medicine were included in the study, and 635 cases (62.7%) were male. The average age was (61±14) years old and the average eGFR decline slope was 4.0%/year. The levels of baseline serum potassium and time-averaged serum potassium of patients in the slow progression group [(4.47±0.52) and (4.51±0.43) mmo/L] and rapid progression group [(4.62±0.62) and (4.76±0.48) mmo/L] were higher than those in the stable group [(4.37±0.49) and (4.38±0.37) mmo/L] (both P<0.05). Meanwhile, 24.6% (83/338) of the patients in the rapid progression group had hyperkalemia at baseline (serum potassium ≥5.0 mmol/L) and 34.9% (118/338) of the patients had time-averaged serum potassium ≥5.0 mmol/L, which were higher than those in the stable group [10.7% (36/337) and 6.5% (22/337)] (both P<0.001). Multivariate logistic regression analysis showed that compared with the stable group, baseline serum potassium (OR=1.843, 95%CI: 1.051-3.234) and time-averaged serum potassium (OR=2.495, 95%CI: 1.040-5.987) were correlated with the rapid progression of CKD. Time-averaged serum potassium ≥5.0 mmol/L was the independent influencing factor for rapid progression of CKD. Conclusions: During the follow-up period, the average level of serum potassium in stage Ⅲ-Ⅴ CKD patients should be controlled under 5.0 mmol/L, which may reduce the risk of rapid decline of renal function.

[Significance of microRNA 216a, 324-5p and 29a expression in peripheral blood in patients with acute pancreatitis and their correlation with liver injury].

Objective: To investigate the significance of microRNA (miR)-216a, miR-324-5p, miR-29a expression in peripheral blood in patients with acute pancreatitis (AP) and their correlation with liver injury. Methods: It was a case-control study design. To select 130 AP patients admitted from June 2017 to May 2019 in the First People's Hospital of Shangqiu, and the patients were divided into mild AP group (MAP group) and moderately severe AP group (SAP group) according to the disease severity, or 54 patients in the liver injury group (20 were MAP and 34 were SAP) and 76 in the non-liver injury group(all were MAP) according to liver injury. And another 40 healthy volunteers were selected as the healthy group. The expressions of miR-216a, miR-324-5p and miR-29a in peripheral blood of MAP group, SAP group, healthy group and liver injury group, non-liver injury group were compared, and the correlation between the miRNA levels and clinical indexes was analyzed. The predictive value of miRNA levels in peripheral blood for AP complicated with liver injury was analyzed by receiver operating characteristic (ROC) curve. Results: The levels of miR-216a and miR-29a in MAP group and SAP group were higher than those in healthy group, and the level of miR-324-5p was lower than that in healthy group (all P<0.01). The levels of miR-216a and miR-29a in SAP group were higher than those in MAP group, and the level of miR-324-5p was lower than that in healthy group (all P<0.01). Balthazar CT Score, acute physiology and chronic health evaluations (APACHE Ⅱ) score, C-reactive protein level, length of hospital stay were positively correlated with the levels of miR-216a and miR-29a in peripheral blood (all P<0.05), and negatively correlated with the levels of miR-324-5p (P<0.05). The levels of miR-216a and miR-29a in the peripheral blood in the liver injury group were higher than those in the non-liver injury group, and they were higher inSAP patients than those in MAP patients in the liver injury group (all P<0.05). The level of miR-324-5p in the peripheral blood in the liver injury group was lower than that in the non-liver injury group, and it was lower in SAP patients than that in MAP patientsin the liver injury group (all P<0.05). The area under ROC curve of miR-216a, miR-324-5p, and miR-29a in peripheral blood to predicate the AP complicated with liver damage was 0.694, 0.750 and 0.814, respectively. Conclusions: The levels of miR-216a and miR-29a increase in peripheral blood and the level of miR-324-5p decreases in patients with AP, and they are closely related to Balthazar CT score, APACHEⅡ score, C-reactive protein and length of hospital stay. The levels of miR-216a, miR-324-5p, miR-29a has certain predictive value for AP with liver injury, of which miR-29a has the highest predictive value.

LINC00114 promoted nasopharyngeal carcinoma progression and radioresistance in vitro and in vivo through regulating ERK/JNK signaling pathway via targeting miR-203.

OBJECTIVE: Nasopharyngeal carcinoma (NPC) is a malignancy and is prone to distant metastasis and radioresistance. Long non-coding RNAs (lncRNAs) play vital roles in human cancers. The purpose of this study was to explore the role and the action mechanism of intergenic lncRNA (LINC00114) in NPC. MATERIALS AND METHODS: The expression of LINC00114 and microRNA-203 (miR-203) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). NPC cells were exposed to X-ray as radiation treatment. Cell proliferation, migration, cell survival fraction and apoptosis were assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), transwell, colony formation, and flow cytometry assays, respectively. The expression of Cleaved-cas-3, Cleaved-cas-9, phosphor-ERK (p-ERK) and phosphor-JNK (p-JNK) was quantified by Western blot. The interaction between miR-203 and LINC00114 was predicted by bioinformatics tool microRNA.org and verified by dual-luciferase reporter assay. Tumor formation assay in nude mice was conducted to examine the role of LINC00114 in vivo. RESULTS: LINC00114 was upregulated in serums from NPC patients, tissues and cell lines of NPC. LINC00114 knockdown inhibited proliferation, migration, and radioresistance of NPC cells. MiR-203 was a target of LINC00114, and miR-203 inhibition eliminated the effects of LINC00114 knockdown. Besides, the extracellular signal-regulated kinases (ERK)/c-Jun N-terminal kinases (JNK) pathway was inactivated by LINC00114 knockdown but recovered by miR-203 inhibition. Moreover, LINC00114 knockdown suppressed tumor growth and radioresistance in vivo. CONCLUSIONS: LINC00114 contributed to NPC development and radioresistance through the regulation of ERK/JNK signaling pathway and the mediation of miR-203, suggesting that LINC00114 was a promising biomarker to defense NPC progression and radioresistance.

Correlation between neutrophil gelatinase-associated lipocalin and soluble CD14 subtype on the prognosis evaluation of acute paraquat poisoning patients.

OBJECTIVE: The objective of this article is to study the correlation between neutrophil gelatinase-associated lipocalin (NGAL) and soluble CD14 subtype (presepsin) on the severity and prognosis evaluation of acute paraquat poisoning (APP) patients. MATERIALS AND METHODS: We studied 120 APP patients who were divided into three groups: light (28 cases), moderate (52 cases), and heavy poisoning (40 cases) groups. Twenty healthy volunteers were enrolled as controls. RESULTS: Acute kidney injury (AKI) occurred in 86 APP patients (71.7%, 86 of 120). In AKI group, urine NGAL was elevated 3 h after treatment, serum NGAL was elevated 24 h after treatment, and serum creatine (SCr) was elevated 2 days after treatment, which were all significantly higher than non-AKI group. Compared with control group, there were significant differences in presepsin and acute physiology and chronic health status (APACHE) II score of different poisoning groups. There were significant differences in detection indices 24 h, 3 days, and 7 days after treatment among different poisoning groups. There was a positive correlation between urine NGAL and serum paraquat concentration, urine NGAL, and AKI morbidity (r 1 = 0.974, r 2 = 0.766, p < 0.001), suggesting higher urine NGAL level indicated higher AKI morbidity. Receiver operating characteristic curves analysis suggested serum presepsin level and urine NGAL level had higher sensitivity and specificity than APACHE II score when predicting 28-day mortality of APP patients. CONCLUSION: Serum and urine NGAL level is elevated earlier than SCr, which is important for the early diagnosis of APP. Serum presepsin and urine NGAL levels can be used as markers to diagnose the severity of AKI and predict the mortality of APP patients.

[Quantitative evaluation of image quality of megavoltage computed tomography for guiding helical tomotherapy].

OBJECTIVE: To quantitatively analyze image quality of two sets of phantom (CatPhan504 and Cheese) Megavoltage computed tomography (MVCT) images acquired by Helical Tomotherapy with three scanning modes (Fine, Normal and Coarse), and to explore and validate a semi-automatic quality assurance procedure for MVCT images of Helical Tomotherapy. METHODS: On Helical Tomotherapy, CatPan504 and Cheese phantoms were scanned with three pitch levels (Fine, Normal, Coarse: 4 mm, 8 mm, 12 mm/circle) respectively. Pylinac, Matlab and Eclipse were used to calculate and compare spatial resolution, noise level and low contrast resolution of images obtained under three scanning modes respectively. The spatial resolution can be evaluated by the blurring of line-pair CT value in the images of CatPhan504's CTP528 module. The noise level can be evaluated by the integral non-uniformity in the images of Cheese's uniformity module. the low contrast resolution can be evaluated by contrast-to-noise ratio of both phantoms' plug-in module, or visibility of the region of interest (Supra-Slice) in the images of CatPhan504's CTP515 module. RESULTS: Analyses on CatPhan504's line pair module(CTP528 module) showed that the first three line pairs(the gap size are 0.500 cm, 0.250 cm and 0.167 cm respectively) could be clearly observed but blurring began to occur from the fourth line pair(the gap size is 0.125 cm) under Coarse mode. Meanwhile, the first four line pairs were all observable under the Normal and Fine modes. Integral non-integrity index(the value negatively correlated with the noise level) were 0.155 7, 0.136 8 and 0.122 9 for Coarse, Normal and Fine modes respectively. None of the Supra-Slice in CatPhan504's CTP515 module could be observed under three imaging modes. Low contrast contrast-to-noise ratio of Cheese phantom was similar under three modes and the insert visibility exhibited nearly linear growth with the increasing difference between CT average value of the insert material and background. CONCLUSION: Superiority and inferiority of three image modes in terms of the three image quality index was not consistent. Evaluation results above could provide reference for more rational decision on scanning modes selection of helical tomotherapy, which was based on image visualization demands in clinical practice. The proposed method could also provide guidance for similar image quality assessment and periodic quality assurance.

[Relationship between neutrophil-to-lymphocyte ratio and myocardial injury induced by acute carbon monoxide poisoning].

Objective: To investigate the relationship between neutrophil-to-lymphocyte ratio (NLR) and myocardial injury induced by acute carbon monoxide poisoning. Methods: A retrospective analysis was performed on 214 patients with acute carbon monoxide poisoning who were admitted to Emergency Depart-ment of Harrison International Peace Hospital, Hebei Medical University, from 2015 to 2017. According to the diagnostic criteria for toxic heart disease and the level of cardiac troponin I (cTnI), a biomarker of cardiac injury, these patients were divided into myocardial injury group (n = 84) and non-myocardial injury group (n=130). The general information of age and sex, as well as routine blood test results and cardiac injury biomarkers on admission, were collected. NLR was calculated and compared between the two groups. The relationship between NLR and cTnI was analyzed. Logistic regression analysis was used to identify the influenc-ing factors for myocardial injury induced by acute carbon monoxide poisoning. The receiver operating charac-teristic curve was used to evaluate the predictive value of NLR on admission for myocardial injury induced by acute carbon monoxide poisoning. Results: There were significant differences between two groups in male patients, the history of smoking, white blood cell count (WBC), NLR, creatine kinase-MB, and lactate dehydro-genase(P<0.01). In the myocardial injury group, NLR was positively correlated with cTnI (r=0.295, P<0.01). The multivariate logistic regression analysis showed that NLR (odds ratio OR=1.079, 95% confidence inter-val CI: 1.017~1.144, P<0.01), WBC (OR=1.216, 95% CI: 1.098~1.346, P<0.01), and male sex (OR = 2.693, 95% CI: 1.045~6.939, P= 0.05) were independent risk factors for myocardial injury induced by acute carbon monoxide poisoning. In predicting myocardial injury induced by acute carbon monoxide poisoning, NLR on admission had a sensitivity of 85.7% and a specificity of 45.4% at the optimal cut-off value of 4.83. Conclusion: Increased NLR on admission has a certain predictive value for myocardial injury induced by acute carbon monoxide poisoning.

Field-Driven Quantum Criticality in the Spinel Magnet ZnCr_{2}Se_{4}.

We report detailed dc and ac magnetic susceptibilities, specific heat, and thermal conductivity measurements on the frustrated magnet ZnCr_{2}Se_{4}. At low temperatures, with an increasing magnetic field, this spinel material goes through a series of spin state transitions from the helix spin state to the spiral spin state and then to the fully polarized state. Our results indicate a direct quantum phase transition from the spiral spin state to the fully polarized state. As the system approaches the quantum criticality, we find strong quantum fluctuations of the spins with behaviors such as an unconventional T^{2}-dependent specific heat and temperature-independent mean free path for the thermal transport. We complete the full phase diagram of ZnCr_{2}Se_{4} under the external magnetic field and propose the possibility of frustrated quantum criticality with extended densities of critical modes to account for the unusual low-energy excitations in the vicinity of the criticality. Our results reveal that ZnCr_{2}Se_{4} is a rare example of a 3D magnet exhibiting a field-driven quantum criticality with unconventional properties.

[Epidemiological characteristics and molecular typing of typhoid and paratyphoid in China, 2009-2013].

Objective: To understand the epidemiological and molecular characteristics of typhoid and paratyphoid in China from 2009 to 2013, and provide evidence for the prevention and control of typhoid and paratyphoid, the development and improvement of surveillance strategies. Methods: Epidemiological analysis was conducted on the incidence data of typhoid and paratyphoid, and related public health emergencies in China during 2009-2013. Pathogen isolation and culture, serologic test were conducted for the typhoid and paratyphoid cases from 13 national surveillance sites. The isolates were subjected to antimicrobial susceptibility testing. Pulsed-field gel electrophoresis (PFGE) was performed for the molecular typing of these isolates. Results: The average incidence of typhoid and paratyphoid in China during this period was 1.03/100 000. The reported case number and incidence decreased with year. The provinces reporting high case numbers were Yunnan, Guizhou, Guangxi, Hunan, Zhejiang, Guangdong and Xinjiang. The incidence of age group 0-4 years was highest. The proportion of farmers and children outside child care settings showed an increasing tendency over time. The annual incidence peak was during July-August. Twenty five outbreaks occurred during 2009-2013. The results of pathogen isolation and culture showed that the positive rate was 3.00% (940/31 322), among the positive isolates, the proportion of Salmonella paratyphi A accounted for higher proportion (68.19%, 641/940) compared with Salmonella typhi (31.60%, 297/940). The drug resistances of Salmonella typhi and Salmonella paratyphi varied, but their resistances to nalidixic acid were highest (50.22% and 85.33%) respectively. A certain amount of Salmonella typhi isolates showed the resistance to the 3rd generation cephalosporins. PFGE analysis showed divergent patterns of Salmonella typhi compared with limited patterns of Salmonella paratyphi A. Conclusion: The epidemic level of typhoid and paratyphoid in China was relatively low, but the outbreak occurred occasionally. It is necessary to enhance the laboratory-based surveillance, particularly the capability of etiological diagnosis, outbreak investigation, response and antibiotic resistance monitoring, and conduct risk factor investigation in provinces with high incidences in recent years.

[Role of nuclear factor of activated T-cells cytoplasmic 1 on vascular calcification in rats with chronic renal failure].

Objective: To explore the role of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) on vascular calcification in chronic renal failure rats. Methods: Nineteen male Sprague-Dawley (SD) rats were randomly divided into three groups: sham-operated group (n=6), 5/6 Nephrectomy (Nx) group (n=6), 5/6 Nx+ calcitriol group (n=7). Vascular calcification was determined by von Kossa staining and orthocresolphthalein complexone (OCPC) method. Protein expressions of NFATc1 and runt-related transcription factor 2 (Runx2) in aortas were measured by immunohistochemistry.In vitro, vascular smooth muscle cells (VSMCs) were primarily cultured and calcification was induced by ß-glycerophosphate (ß-GP). These cells were then randomly divided into control group, calcification group (10 mmol/L ß-GP) and cyclosporin A (CsA) intervention group (10 mmol/L ß-GP+ 1 µg/ml CsA). Calcium deposition was measured by Alizarin red staining and OCPC method; alkaline phosphatase (ALP) activity was measured by enzyme-linked immunosorbent assay. RT-PCR and Western blotting were used to observe the mRNA and protein expression of VSMCs NFATc1 and Runx2 respectively. Results: Compared to that in sham-operated and 5/6 Nx group, the expression of NFATc1 was obviously up-regulated in 5/6 Nx+ calcitriol group (7.20±0.46 vs 1.52±0.77, 2.04±1.31, P<0.05). In vitro, VSMCs calcification was successfully induced by high phosphorus environment, and RT-PCR and Western blotting showed that the expressions of NFATc1 and Runx2 were up-regulated (P<0.05). The calcification level in CsA intervention group was lower than that in calcification group [(60.86±7.95) vs (107.20±11.07) mg/g, P<0.05], and expression of Runx2 (mRNA and protein level) and ALP activity [(48.63±3.02) vs (98.75±3.46) U/g, P<0.05] decreased as well. Conclusion: NFATc1 contributes to accelerating vascular calcification in rat with chronic renal failure, the possible mechanism of which is that NFATc1 promotes VSMCs transformation to osteogenic phenotype.

TNFα-activated mesenchymal stromal cells promote breast cancer metastasis by recruiting CXCR2+ neutrophils.

Mesenchymal stromal cells (MSCs) tend to infiltrate into tumors and form a major component of the tumor microenvironment. Our previous work demonstrated that tumor necrosis factor α (TNFα)-activated MSCs significantly promoted tumor growth. However, the role of TNFα-treated MSCs in tumor metastasis remains elusive. Employing a lung metastasis model of murine breast cancer, we found that TNFα-activated MSCs strikingly enhanced tumor metastasis compared with normal MSCs. We analyzed the chemokine profiles and found that the expression of CCL5, CCR2 and CXCR2 ligands were enhanced in TNFα-activated MSCs. Using genetic or pharmacological strategies to inhibit CCL5 or CCR2, we demonstrated that CCL5 and CCR2 ligands were indispensable in supporting TNFα-activated MSCs to promote tumor metastasis. Analysis of immune cells revealed that CXCR2 ligands (CXCL1, CXCL 2 and CXCL5) expressed by TNFα-activated MSCs efficiently recruited CXCR2+ neutrophils into tumor. These neutrophils were responsible for the pro-metastatic effect of MSCs since inhibition of this chemotaxis abolished increased neutrophil recruitment and tumor metastasis. The interaction between neutrophils and tumor cells resulted in markedly elevated metastasis-related genes by tumor cells, including CXCR4, CXCR7, MMP12, MMP13, IL-6 and TGFß. Importantly, in IL8high human breast cancer samples, we also observed similar alterations of gene expression. Collectively, our findings demonstrate that TNFα-activated MSCs promote tumor metastasis via CXCR2+ neutrophil recruitment.

Role of the lens in controlling physical dormancy break and germination of Delonix regia (Fabaceae: Caesalpinioideae).

Physical dormancy occurs in all three subfamilies of Fabaceae, namely Mimosoideae, Papilionoideae and Caesalpinioideae, making it one of the largest plant families in terms of number of species with physical dormancy. However, little is known about the water gap structure and germination ecology of species in Caesalpinioideae. Freshly collected seeds of Delonix regia (Caesalpinioideae) did not imbibe water, thus they had physical dormancy. Both dry heat and wet heat were effective in breaking dormancy, however, longer duration was required at 80 °C and shorter duration at 90 °C. Seeds buried in the field for 2 years germinated to 21% and 42% after the first and second summer, respectively, compared with 3% germination in seeds at the time of maturity. Seeds incubated at 15/60 °C in the laboratory (mimicking summer conditions) for 3 months supported this conclusion, as dormancy was relieved in 18% and 24% of seeds stored dry and watered intermediately, respectively. All the dormancy breaking treatments resulted in lifting of palisade layers in the lens region to form a circular lid-like opening, i.e. water gap (Type II simple). Blocking experiments confirmed that water entered only through the lens and no secondary water entry point was observed. No apparent changes in morphology/anatomy of the hilum region were noted in dormant and non-dormant (water permeable) seeds. These results suggest that summer temperatures could open the lens in a proportion of seeds every year and that germination occurs during the subsequent wet season in the tropics.

Downregulation of CXCL12 in mesenchymal stromal cells by TGFß promotes breast cancer metastasis.

Mesenchymal stromal cells (MSCs) are one of major components of the tumour microenvironment. Recent studies have shown that MSC tumour residence and their close interactions with inflammatory factors are important factors that affect tumour progression. Among tumour-associated inflammatory factors, transforming growth factor ß (TGFß) is regarded as a key determinant of malignancy. By employing a lung metastasis model of a murine breast cancer, we show here that the prometastatic effect of MSCs was dependent on their response to TGFß. Interestingly, we found that MSC-produced CXCL12, an important chemokine in tumour metastasis, was markedly inhibited by TGFß. Furthermore, silencing of CXCL12 in TGFß-unresponsive MSCs restored their ability to promote tumour metastasis. We found that 4T1 breast cancer cells expressed high levels of CXCR7, but not of CXCR4, both of which are CXCL12 receptors. In presence of CXCL12, CXCR7 expression on tumour cells was decreased. Indeed, when CXCR7 was silenced in breast cancer cells, their metastatic ability was inhibited. Therefore, our data demonstrated that sustained expression of CXCL12 by MSCs in the primary tumour site inhibits metastasis through reduction of CXCR7, while, in the presence of TGFß, this CXCL12 effect of MSCs on tumour cells is relieved. Importantly, elevated CXCR7 and depressed CXCL12 expression levels were prominent features of clinical breast cancer lesions and were related significantly with poor survival. Our findings reveal a novel mechanism of MSC effects on malignant cells through which crosstalk between MSCs and TGFß regulates tumour metastasis.

[Clinical value of serum presepsin (SCD14-ST) concentration measurement in patients with pesticide poisoning].

OBJECTIVE: To investigate the value of serum presepsin concentration measurement in the clinical diagnosis and treatment of patients with pesticide poisoning patients. METHODS: A total of 160 patients with pesticide poisoning were enrolled as study subjects and divided into moderate organophosphate pesticide poisoning group (40 patients) , severe organophosphate pesticide poisoning group (40 patients) , abamectin pesticide poisoning group (40 patients) , and paraquat poisoning group (40 patients). A total of 20 healthy volunteers were enrolled as the control group. All the patients with poisoning received conventional treatment of pesticide poisoning immediately after admission, and serum presepsin concentration was measured on days 1 (within 24 hours after poisoning) , 3, and 7 of admission, and biochemical and radiological parameters related to the patient's condition were also examined. The patients with a Presepsin concentration of >800 pg/ml on day 1 of admission were randomly divided into conventional treatment group and ulinastatin treatment group, and the treatment outcome was compared between the two groups. RESULTS: Compared with the healthy control group, the groups with pesticide poisoning showed significant increases in serum Presepsin concentrations, with the highest degree of increase on day 1 (P <0.05). The serum Presepsin concentration was positively correlated with alanine aminotransferase, aspartate aminotransferase, creatine kinase, creatine kinase MB, lactate dehydrogenase, serum creatinine, blood urea nitrogen, interleukin-18, and white blood cell count, but negatively correlated with cholinesterase. In the conventional treatment group and ulinastatin treatment group, the overall response rate was 68% and 78.8%, respectively, with a significant difference between the two groups (P<0.05). In 40 patients with paraquat poisoning, 32 experienced an increase in serum presepsin concentration, and among these 32 patients, 27 (83%) experienced exudation on lung CT. CONCLUSION: Serum Presepsin concentration measurement can assist early diagnosis, evaluation of disease severity, and guidance for clinical medication in patients with pesticide poisoning, especially in those with severe pesticide poisoning and a tendency to multiple organ failure.

TonEBP modulates the protective effect of taurine in ischemia-induced cytotoxicity in cardiomyocytes.

Taurine, which is found at high concentration in the heart, exerts several protective actions on myocardium. Physically, the high level of taurine in heart is maintained by a taurine transporter (TauT), the expression of which is suppressed under ischemic insult. Although taurine supplementation upregulates TauT expression, elevates the intracellular taurine content and ameliorates the ischemic injury of cardiomyocytes (CMs), little is known about the regulatory mechanisms of taurine governing TauT expression under ischemia. In this study, we describe the TonE (tonicity-responsive element)/TonEBP (TonE-binding protein) pathway involved in the taurine-regulated TauT expression in ischemic CMs. Taurine inhibited the ubiquitin-dependent proteasomal degradation of TonEBP, promoted the translocation of TonEBP into the nucleus, enhanced TauT promoter activity and finally upregulated TauT expression in CMs. In addition, we observed that TonEBP had an anti-apoptotic and anti-oxidative role in CMs under ischemia. Moreover, the protective effects of taurine on myocardial ischemia were TonEBP dependent. Collectively, our findings suggest that TonEBP is a core molecule in the protective mechanism of taurine in CMs under ischemic insult.

First Report of Brown Culm Streak of Phyllostachys praecox Caused by Arthrinium arundinis in Nanjing, China.

Early spring shoot bamboo (Phyllostachys praecox) is profitable for the production of bamboo shoots and is widely cultivated in Jiangsu and Zhejiang provinces in China. In recent years, a new disease named brown culm streak has commonly occurred in bamboo plantations. During initial stages, small yellow or sandy beige spots (1 to 2 mm diameter) develop on the culm. Spots expand and develop into fine brown streaks (10 to 15 × 1 to 2 mm), and the quantity of spots increases greatly at the mid-stage of the disease. The streaks continue to expand (10 to 30 × 2 to 3 mm) and may coalesce into brown patches that cover 70% of the culm surface in late stages of disease. Color of the internal bamboo cavity gradually changes from white to brown without an alcoholic odor, and plants eventually die. Diseased tissues (1 × 1.5 cm) were taken from the edges of brown streaks, surface disinfected in 0.1% HgCl2 for 3 min, rinsed in distilled water three times, and incubated on potato dextrose agar (PDA) at 25°C. Based on colony and conidial morphology, six different fungi (ZBY01, ZBY02, ZBY03, ZBY04, ZBY05, and ZBY06) were isolated. A suspension of hyphal fragments (106 pieces/ml) of each of the fungi was used to inoculate plants in the field. Healthy bamboo culms were stabbed with alcohol-sterilized needles after surface disinfection and wounds of each bamboo were inoculated with 3 ml hypha fragment suspensions by paintbrush, then covered with a piece of sterile plastic film. A control treatment was inoculated with sterile water. Each treatment had two replicates. Twenty days after inoculation, only fungus ZBY01 caused similar symptoms with the diseased bamboo in the field and was re-isolated from necrotic tissue of inoculated plants, thus fulfilling Koch's postulates. Mycelium of fungus ZBY01 covered entire PDA plates (90 mm diameter) after incubating for 6 days at 25°C and was white, flat, and floccose with moderate aerial mycelium. Mycelium consisted of smooth, hyaline, branched, septate hyphae, 2 to 3 µm diameter. Conidiophores were erect, septate, pale brown, smooth, and reduced to conidiogenous cells. Conidiogenous cells were pale brown, smooth, ampulliform, 6 to 9 µm long; the apical neck was 1 to 3 µm long, basal part 5 to 6 µm long. Conidia were 1-celled, dark brown to black, smooth, lenticular, 5 to 7 µm in diameter, 2 to 4 µm wide, lemon-shaped in side view, and spherical from top view with an equatorial ring. Based on morphological characteristics, it was identified as Arthrinium arundinis (Corda) Dyko & B. Sutton (1). The internal transcribed spacer (ITS) region from the isolate ZBY01 was amplified with PCR using ITS1-ITS4 primer pairs and the amplicon sequenced. Size of the sequenced region was 540 bp and had 99% identity with A. arundinis, which was in accord with morphological identification. The sequence was deposited in Gen Bank under accession number KF850624. To our knowledge, brown culm streak of P. praecox is a new disease of bamboo that has not been reported in other countries; however, A. arundinis has been reported as a pathogen on barley in Fairfield, Montana. Reference: (1) P. W. Crous and J. Z. Groenewald. A phylogenetic re-evaluation of Arthrinium. IMA Fungus. 4:133, 2013.