[Associations between serum GDF15 and glycolipid metabolism disorder in metabolic associated fatty liver patients].

Objective: To investigate relationships between serum growth differentiation factor 15 (GDF15) and glycolipid metabolism in patients with metabolic associated fatty liver disease (MAFLD). Methods: The current investigation was a cross-sectional study. A total of 333 patients from the Fengxian District Central Hospital were recruited into the study after physical examination from February 2020 to February 2021. There were 107 patients with MAFLD and type 2 diabetes mellitus (T2DM), including 54 males and 53 females with a mean age of (57±11) years. There were 65 patients with simple MAFLD only, including 32 men and 33 women with a mean age of (49±5) years. There were 105 patients with T2DM only, including 53 men and 52 women, with a mean age of (56±10) years. A control group of 56 people without MAFLD or diabetes,28 male, 28 female, mean age (48±6) years, was also included in the study. Serum GDF15 was measured via enzyme-linked immunosorbent assays. IBM SPSS 26.0 was used for statistical analysis. Logistic regression was used to evaluate relationships between GDF15 and metabolic abnormalities in MAFLD patients. Results: GDF15 progressively increased in the control [385 (296, 484) ng/L], nonobese MAFLD [388 (319, 435) ng/L], obese MAFLD [426 (354, 527) ng/L], T2DM [664 (483, 900) ng/L], and MAFLD+T2DM groups [770 (560, 1 074) ng/L](H=113.82, P=0.001). There was no significant difference in serum GDF15 between the simple MAFLD [406 (339, 524) ng/L] and control group (U=1 505.50, P=0.132). GDF15 was significantly higher in the MAFLD+T2DM group than in the T2DM-only group (U=4 573.50, P=0.019). In logistic regression analysis increased GDF15 was associated with increased risks of simple MAFLD [odds ratio (OR)=2.202], T2DM (OR=29.656), and MAFLD+T2DM(OR=58.197). In patients with MAFLD, serum GDF15 was higher in the FIB4 index>1.45 group [773 (534, 1 162) ng/L] than in the FIB4 index<1.45 group [527 (389, 787) ng/L] (U=1 709.50, P<0.001). Increased GDF15 was associated with an increased risk of advanced liver fibrosis (OR=2.388). Conclusion: In patients with simple MAFLD, GDF15 level was not significantly higher than in the control group. In the T2DM-only group and the MAFLD+T2DM group GDF15 was significantly higher than in the control group. Increased serum GDF15 was associated with increased risk and severity of MAFLD complicated with abnormal glucose and lipid metabolism. High GDF15 increased the risk of advanced fibrosis in MAFLD patients.

[Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer].

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.

[Clinical efficacy analysis of functional rhinoplasty assisted by nasal endoscopy].

Objective: To analyse the clinical effect of endoscopy-assisted functional rhinoplasty. Methods: Twenty-one patients with congenital or traumatic deviated nose with nasal obstruction admitted to Qilu Hospital (Qingdao) from January 2018 to December 2021, including 8 males and 13 females, aged 22 to 46 years, were retrospectively analysed. Endoscopy-assisted functional rhinoplasty was performed in all patients. Deviated nasal septum was corrected, nasal septum cartilage graft was prepared through open approach assisted by endoscopy, the nasal frame structure was adjusted with the endoscopy-assisted rhinoplasty combined with middle and inferior turbinoplasty, and the patient's nasal ventilation function and external nose cosmetology were restored. Visual Analogue Scale (VAS), Nasal Obstruction Symptom Evaluation (NOSE), nasal acoustic reflex and nasal resistance were examined preoperatively and 6 months postoperatively. The minimum cross-sectional area of the first two nasal cavities (MCA) MCA1 and MCA2 and their distance between nostrils to the minimum cross-sectional area (MD) MD1 and MD2 were recorded, and the ratio of both sides (expressed in a/b) was calculated. The nasal volume of 5 cm depth from nostril (NV5) and nasal resistance total (RT) were recorded to evaluate the nasal ventilation function to analyse the clinical effect of functional rhinoplasty assisted by nasal endoscope. SPSS 25.0 software was used for statistical analysis. Results: At 6 months after the operation, for nasal ventilation evaluation, the VAS and NOSE scores of nasal obstruction decreased significantly than those before the operation ((1.81±0.81) points vs (6.71±1.38) points, (4.19±2.06) points vs (12.05±2.67) points, all P<0.05). In the objective indexes, MCA1, MCA2 and NV5 were significantly increased whereas RT, MCA1a/MCA1b, MCA2a/MCA2b, MD1a/MD1b and MD2a/MD2b were significantly decreased compared with those before the operation (all P<0.05). The MD1 and MD2 levels before and after operation had no significant differences (all P>0.05). In the evaluation of external nose morphology, postoperative ROE was significantly increased, and the deviation value of nasal appearance was significantly decreased ((16.19±2.56) points vs (10.24±3.24) points, (1.55±1.16) mm vs (5.63±2.41) mm, all P<0.05). In terms of postoperative patient satisfaction, 19 cases (90.5%) were very satisfied with nasal ventilation function, 2 cases (9.5%) were satisfied with nasal ventilation function; 15 cases (71.4%) were very satisfied with nasal appearance, and 6 cases (28.6%) were satisfied with nasal appearance. Conclusions: Nasal endoscopy-assisted functional rhinoplasty can improve the nasal ventilation function and external nasal morphology at the same time, with good clinical effect and high patient satisfaction.

[Analysis of the feasibility and prognostic value of circulating tumor DNA in detecting gene mutations in small cell lung cancer].

Objective: To investigate the feasibility of circulating tumor DNA (ctDNA) in detecting small cell lung cancer (SCLC) gene mutations and its prognostic value in chemotherapy and/or radiotherapy for SCLC patients. Methods: A total of 77 SCLC patients who were admitted to the Department of Thoracic Medical Oncology and the Department of Thoracic Radiation Oncology of Zhejiang Cancer Hospital from July 2016 to November 2019 were included. There were 66 males and 11 females, with a median age of 60 years. Among them, 42 cases were in limited stage (LS) and 35 cases were in extensive stage (ES). Next-generation sequencing (NGS) of patients' plasma ctDNA was performed before treatment. The differences of mutated genes and signaling pathways between LS and ES patients were analyzed and compared. Blood-based tumor mutation burden (bTMB) was calculated according to detected somatic cell mutations. Patients were divided into the high bTMB and the low bTMB groups according to the optimal threshold calculated by R software. Log-rank tests were used to compare progression-free survival (PFS) between the high bTMB and the low bTMB groups. Results: Among the 77 patients, 76 patients had gene mutations detected in their plasma, and the positive rate of ctDNA test was 98%. Among the 76 patients, the genes with the highest mutation frequency were TP53 (89%), RB1 (70%), LRP1B (34%), CREBBP (21%), MLL3 (21%), MLL2 (16%), NOTCH1 (13%), ROS1 (13%), BRCA2 (12%), and PTPRD (12%). The most common mutated genes in LS patients were TP53 (90%), RB1 (68%), LRP1B (24%), MLL2 (22%), and BRCA2 (17%); the most common mutated genes in ES patients were TP53 (89%), RB1 (71%), LRP1B (46%), CREBBP (31%), and MLL3 (29%). The mutation rates of NOTCH1 and CREBBP genes were significantly higher in ES patients (31.4% and 22.9%) than those in LS patients (11.9% and 4.8%) (both P<0.05). Signaling pathway analysis showed that there were more NOTCH pathway gene variations in ES patients. Among LS patients, patients in the high bTMB group (≥ 6.96 mutations/Mb) had a longer PFS than that in the low bTMB group (<6.96 mutations/Mb) (P=0.033); but no such difference was noted in ES patients. Conclusion: Plasma ctDNA sequencing detected SCLC gene mutation profiles similar to those reported in previous literature, thus ctDNA could be used as a tool to study SCLC genomics; the mutation spectra of ES-SCLC and LS-SCLC were different. bTMB has potential prognostic value in LS-SCLCs treated with chemoradiotherapy.

[Prognostic value of myocardial injury in patients with COVID-19].

Objective: To analyze the prognostic value of myocardial injury in patients with COVID-19. Method: Confirmed cases of COVID-19 patients admitted from January 31st to February 5th at isolation ward of Renmin Hospital of Wuhan University were divided into non-survival group （33 cases）and survival group (169 cases)according to the clinical outcomes 5 weeks after admission. Data including demographics, comorbidities, vital signs, laboratory results were obtained. Cardiac injury was defined as serum concentration of high sensitivity cardiac troponin I (hs-cTnI) above 0.04 µg/L. Univariate and multivariate Cox regression were used to analyze the prognostic value of myocardial injury in patients with COVID-19. Kaplan-Meier analysis was used to plotted survival curve and analyze the impact of myocardial injury on the survival outcome of COVID-19 patients. Results: A total of 202 patients were included, the age was 63 (51, 70) years old, 88 (43.6%) of them were male, 85 (42.1%) of them had comorbidities, 125 (61.9%) of them were severely to critically ill. Till March 11, 33 patients died, all of them were critically ill patients. The age, proportion of males, comorbidities, respire rate, serum levels of hs-cTnI and incidence of heart failure in the non-survival group were significantly higher than those in the survival group (all P<0.05). The hospitalization time of non-survival group was significantly shorter than that of survival group (6(4, 9) vs. 32(23, 36), P<0.001). Myocardial injury was an important prognostic factor of COVID-19 (HR=5.382, 95%CI 2.404-12.050, P<0.001). Kaplan-Meier survival analysis showed that the presence of myocardial injury was significantly associated with the reduced survival rate among COVID-19 patients (P<0.001). Conclusion: Myocardial injury is an important prognostic factor of COVID-19, COVID-19 patients with myocardial injury face a significantly higher risk of death.

[Prognostic value of myocardial injury in patients with COVID-19].

Objective: To analyze the prognostic value of myocardial injury in patients with COVID-19. Method: Confirmed cases of COVID-19 patients admitted from January 31st to February 5th at isolation ward of Renmin Hospital of Wuhan University were divided into non-survival group and survival group according to the clinical outcomes 5 weeks after admission. Data including demographics, comorbidities, vital signs, laboratory results were obtained. Cardiac injury was defined as serum concentration of high sensitivity cardiac troponin I (hs-cTnI) above 0.04 µg/L. Univariate and multivariate Cox regression were used to analyze the prognostic value of myocardial injury in patients with COVID-19. Kaplan-Meier analysis was used to plotted survival curve and analyze the impact of myocardial injury on the survival outcome of COVID-19 patients. Results: A total of 202 patients were included, the age was 63 (51, 70) years old, 88 (43.6%) of them were male, 85 (42.1%) of them had comorbidities, 125 (61.9%) of them were severely to critically ill. Till March 11, 33 patients died, all of them were critically ill patients. The age, proportion of males, comorbidities, respire rate, serum levels of hs-cTnI and incidence of heart failure in the non-survival group were significantly higher than those in the survival group (all P<0.05). The hospitalization time of non-survival group was significantly shorter than that of survival group (6(4, 9) vs. 32(23, 36), P<0.001). Myocardial injury was an important prognostic factor of COVID-19 (HR=5.382, 95%CI 2.404-12.05, P<0.001). Kaplan-Meier survival analysis showed that the presence of myocardial injury was significantly associated with the reduced survival rate among COVID-19 patients (P<0.001). Conclusion: Myocardial injury is an important prognostic factor of COVID-19, COVID-19 patients with myocardial injury face a significantly higher risk of death.

Immune efficacy of a porcine circovirus type 2 vaccine purified using Gram-positive enhancer matrix surface display technology.

AIMS: Purification of porcine circovirus type 2 (PCV2) using Gram-positive enhancer matrix (GEM) surface display technology and immunogenicity evaluation of the purified antigen. METHODS AND RESULTS: A recombinant bifunctional protein containing a protein anchor domain and a 'virus anchor' domain was designed as a protein linker (PL) between PCV2 and GEM particles. By incubating with PL and GEM particles sequentially, PCV2 could be purified and enriched through a simple centrifugation process with GEM surface display technology. Our data showed that one unit (2·5 × 109 particles) of GEM particles with 80 µg PL could purify 100 ml of PCV2-containing culture supernatant (viral titre: 106·5 TCID50 per ml-1 ) with a recovery rate up to 99·6%. The impurity removal efficiency of this method, calculated according to decreased total protein content during purification, was approximately 98%. Furthermore, in vivo experimentation showed that piglets immunized with purified PCV2 could elicit strong immune responses to prevent against PCV2 infection. CONCLUSION: Porcine circovirus type 2 could be efficiently purified and enriched with GEM display technology via a crucial PL, and the purified PCV2 could elicit effective immune responses against PCV2 infection. SIGNIFICANCE AND IMPACT OF THE STUDY: The GEM-based purification method established here is cost-efficient and high-throughput, and may represent a promising large-scale purification method for PCV2 vaccine production.

[Surgical treatment of external auricular cholesteatoma involving tympanum and papilloma].

Objective:To explore the operation treatments and their outcomes of external auditory canal cholesteatomas involving the tympanic cavity and mastoid process. Method:Forty-two patients (45 ears) with external auditory canal cholesteatomas were included in this study who were operated. All lesions invaded the tympanic cavity and mastoid process. Excision of cholesteatoma, external auditory canal angioplasty and concha formation were performed. Ossicular chain reconstruction was performed in 3 ears. Mastoidectomy with close technique were performed in 4 ears. Open radical mastoidectomy was performed in 5 ears. Posterior bone-wall of auricular meatus reconstruction was performed in 3 ears. Tympanoplasty was performed in 21 ears. Pure tone audiogram and aural endoscope were carried out after the operation (3 months, 6months, 1 year, 2 years, 3 years…). Result:Stricture of external auditory meatus were occured in 2 ears in 2 and 3 months after surgery respectively. Cholesteatoma recurrence was observed in 2 ears in 1 year after operation. Wet ear was observed in 1 patient and then another operation was performed after 7 months. Besides the patients above, the epitheliums of the cavity were well in all other patients with complete tympanic membranes. Hearing was improved in all patients (hearing by air conduction:5－30 dB HL). Conclusion:According to the range of the external auditory canal cholesteatoma, we took different operation methods including tympanoplasty, open or close radical mastoidectomy and reconstruction of posterior wall of external auditory canal etc. Those methods, including external auditory canal angioplasty, cavity plasty of concha and skin grafting of external auditory canal, could help to prevent scar formation and stricture of external auditory canal, prevent cholesteatoma recurrence and improve hearing.

[Study on the correlation between meteorological factors and acute otitis media in outpatients of children in Beijing].

Objective: To explore the characteristics of acute otitis media(AOM) in children in Beijing and its correlation with meteorological factors. Methods: Data were collected in 2011-2013 in the Otolaryngology Department of Capital Institute of Pediatrics. AOM in children with relevant information, such as age, sex and season, with the same period of the Beijing municipal meteorological data (the average temperature, average pressure, average wind speed, humidity and PM2.5) were compared to analysis the relationship of meteorological environmental parameters and the onset of AOM in children. Results: Annual morbidity of AOM was 7 589, 8 245, 7 242 respectively, no obvious difference(P=0.761). It was noted that one peak could be seen in December, and a valley in February, followed by August. Summer was less than the other three seasons (P<0.05). The morbidity of AOM had a small peak within one year after birth, then reached peak at the age of about 4, and then reduced gradually. In different age groups, male patients were higher than those of female. The incidence of AOM was positively correlation tendency with air pressure and PM2.5 (r=0.333, 0.093, P=0.000, 0.002), which was negatively correlation tendency with daily temperature or humidity (r=-0.327, -0.195, P=0.000, 0.000). Conclusions: The incidence of AOM of children in Beijing changes with age, and has obvious seasonal variation. There may be some correlation between the meteorological factors and the incidence of AOM in children.

Analysis of allopolyploidy-induced rapid genetic and epigenetic changes and their relationship in wheat.

We used the conventional and methylation-sensitive randomly amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) analyses to assess genome-wide changes and explore the relationships between genetic and epigenetic variations among individuals of a newly synthesized allohexaploid wheat line whose genomic constitution is identical to that of the natural common wheat, compared with its parent plants and a natural counterpart named Chinese Spring. We found rapid, extensive, and predominantly consistent non-Mendelian changes in the form of genetic and DNA methylation variations in the allohexaploid individuals. Specifically, at least 30-40% of the epigenetic component was truly independent of genetic changes, which answered a critical question, i.e. its autonomy in relation to the genetic context. Striking correlations were detected between genetic and epigenetic changes. Interestingly, as previously reported, the paternally donated nuclear genomes showed more genetic changes than the maternally donated ones; the loss of paternal bands was significantly correlated with the hypomethylation of CG or CHG sequences, suggesting an unknown link between genetic instability and hypomethylation. Sequence analysis indicated that most variations occurred in the cellular genes and sequences related to transposable elements. Based on these findings, the possible mechanisms and effects of the genomic changes in allopolyploid speciation and evolution were discussed.

Reduction of soy isoflavones by use of Escherichia coli whole-cell biocatalyst expressing isoflavone reductase under aerobic conditions.

UNLABELLED: Soy isoflavone metabolites are currently receiving much attention due to the stronger and wider bioactivities than that of isoflavones. Therefore, biosynthesis of isoflavone metabolites by isolated isoflavone biotransforming bacteria is important. However, the biosynthesis process must be under obligate anaerobic conditions due to the reduction reactions catalysed by isoflavone biotransforming bacteria. In this study, we cloned the daidzein and genistein reductase gene (dgr) from Slackia sp. AUH-JLC159. The recombinant Escherichia coli (E. coli) whole-cell was used for the first time as the biocatalyst for aerobic biosynthesis of dihydrodaidzein (DHD) and dihydrogenistein (DHG) from soy isoflavones daidzein and genistein. Our results indicated that the recombinant E. coli whole-cell was able to reduce daidzein and genistein to DHD and DHG under aerobic conditions, while the maximal concentration of the substrate daidzein or genistein that the E. coli whole-cell was able to convert efficiently was only 0·4 mmol l(-1) . Under the optimized conditions, the maximal concentration of daidzein or genistein that the E. coli whole-cell was able to convert efficiently was increased to 1·4 mmol l(-1) . Our results demonstrated that E. coli whole-cell is an efficient biocatalyst for biosynthesis of isoflavone metabolites under aerobic conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: Soy isoflavone metabolites, which are more biologically active than their precursor isoflavones, are currently receiving much more attention. However, the non-natural isoflavone metabolites are synthesized or biosynthesized under obligate anaerobic conditions. Here, we describe a new approach to the reduction of soy isoflavones daidzein and genistein under aerobic conditions by use of the recombinant Escherichia coli whole-cell expressing isoflavone reductase. Our study provides the first evidence that isoflavone metabolites, such as dihydrodaidzein and dihydrogenistein, are able to be produced efficiently under aerobic conditions.

Glyphosate biodegradation and potential soil bioremediation by Bacillus subtilis strain Bs-15.

Glyphosate and glyphosate-containing herbicides have an adverse effect on mammals, humans, and soil microbial ecosystems. Therefore, it is important to develop methods for enhancing glyphosate degradation in soil through bioremediation. We investigated the potential of glyphosate degradation and bioremediation in soil by Bacillus subtilis Bs-15. Bs-15 grew well at high concentrations of glyphosate; the maximum concentration tolerated by Bs-15 reached 40,000 mg/L. The optimal conditions for bacterial growth and glyphosate degradation were less than 10,000 mg/L glyphosate, with a temperature of 35°C and a pH of 8.0. Optimal fermentation occurred at 180 rpm for 60 h with an inoculum ratio of 4%. Bs-15 degraded 17.65% (12 h) to 66.97% (96 h) of glyphosate in sterile soil and 19.01% (12 h) to 71.57% (96 h) in unsterilized soil. Using a BIOLOG ECO plate test, we observed no significant difference in average well color development values between the soil inoculated with Bs-15 and the control soil before 72 h, although there was a significant difference (P < 0.01) after 72 h. In the presence of Bs-15, the 5 functional diversity indices (Shannon index, Shannon uniformity, Simpson index, McIntosh index, and McIntosh uniformity) were greater (P < 0.01) compared with the control soil. These results indicate that Bs-15 could be used to alleviate contamination from glyphosate-containing herbicides, increasing the microbial functional diversity in glyphosate-contaminated soils and thus enhancing the bioremediation of glyphosate-contaminated soils.

Exploring laccase genes from plant pathogen genomes: a bioinformatic approach.

To date, research on laccases has mostly been focused on plant and fungal laccases and their current use in biotechnological applications. In contrast, little is known about laccases from plant pathogens, although recent rapid progress in whole genome sequencing of an increasing number of organisms has facilitated their identification and ascertainment of their origins. In this study, a comparative analysis was performed to elucidate the distribution of laccases among bacteria, fungi, and oomycetes, and, through comparison of their amino acids, to determine the relationships between them. We retrieved the laccase genes for the 20 publicly available plant pathogen genomes. From these, 125 laccase genes were identified in total, including seven in bacterial genomes, 101 in fungal genomes, and 17 in oomycete genomes. Most of the predicted protein models of these genes shared typical fungal laccase characteristics, possessing four conserved domains with one cysteine and ten histidine residues at these domains. Phylogenetic analysis illustrated that laccases from bacteria and oomycetes were grouped into two distinct clades, whereas fungal laccases clustered in three main clades. These results provide the theoretical groundwork regarding the role of laccases in plant pathogens and might be used to guide future research into these enzymes.

Expression of claudin-1 and its relationship with lymphatic microvessel generation in hypopharyngeal squamous cell carcinoma.

We investigated the relationship between claudin-1 and micro-lymphatic vessel density (MLVD) by detecting claudin-1 and protein D2-40 expression in cancer tissue specimens obtained from 97 patients with hypopharyngeal squamous cell carcinoma (HSCC). We also explored the correlation between the expression of these proteins and clinical tumor stage, pathological grading, and clinical prognosis in the patients. Moreover, we studied the mechanism of lymph node metastasis in HSCC, thereby providing information for treating HSCC and inhibiting lymph node metastasis. We detected levels of claudin-1 and protein D2-40 expression in cancer tissue from 97 patients with HSCC and para-tumor tissue from 90 patients by immunohistochemistry; we analyzed the correlation between markers and clinicopathological features by using the Pearson chi-square test and conducted survival analysis by the log-rank test. Claudin-1 expression was high in HSCC and was related to tumor differentiation and lymph node metastasis; Kaplan-Meier analysis showed that claudin-1 expression was related to patient survival rate (P = 0.012). There was a significant relationship between MLVD in the tissues adjacent to the carcinoma and the indices of histopathological grade, clinical stage, and lymph node metastasis. There was also a positive correlation between claudin-1 expression and MLVD. High expression of claudin-1 might induce the generation of tumor lymphatic vessels, which increases metastasis in the lymph node. Because claudin-1 is related to patient survival rate, it may be useful as a monitoring index for postoperative HSCC and might be a new target for treating the disease.

Analysis of the expression of HMGB-1, CXCL16, miRNA-30a, and TGF-ß1 in primary nephritic syndrome patients and its significance.

We investigated the expression levels of high-mobility group box protein 1 (HMGB-1), CXC chemokine ligand 16 (CXCL16), microRNA (miRNA)-30a and transforming growth factor ß1 (TGF-ß1) in primary nephritic syndrome (PNS) patients and the clinical significance of this expression. A total of 56 patients with PNS were included in the PNS group, while 50 healthy subjects formed the normal control group. Serum levels of HMGB-1, CXCL16, miRNA-30a, and urinary TGF-ß1 concentrations were quantified along with other biochemical indices, including serum albumin, triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein, and urinary proteins. The correlation between levels of HMGB-1, CXCL16, miRNA-30a, and TGF-ß1 and biochemical indexes was further analyzed. PNS group patients had significantly higher levels of HMGB-1, CXCL16, miRNA- 30a, and TGF-ß1 compared to the control group (P < 0.05). PNS patients also had higher 24-h urinary protein, TG, TC, and LDL levels but lower serum albumin compared to subjects in the control group (P < 0.05). Serum HMGB-1, CXCL16, miRNA-30a, and urinary TGF-ß1 levels were all negatively correlated with serum albumin levels, but were positively correlated with TG, TC, LDL, and 24-h urinary protein (P < 0.05 in all cases). Additionally, a positive correlation existed among serum HMGB-1, CXCL16, miRNA-30a, and urinary TGF-ß1 levels (P < 0.01). HMGB-1, CXCL16, miRNA-30a, and urinary TGF-ß1 were highly expressed in PNS patients and may play important roles in the pathogenesis and development of PNS.

Novel analogs targeting histone deacetylase suppress aggressive thyroid cancer cell growth and induce re-differentiation.

To develop novel therapies for aggressive thyroid cancers, we have synthesized a collection of histone deacetylase (HDAC) inhibitor analogs named AB1 to AB13, which have different linkers between a metal chelating group and a hydrophobic cap. The purpose of this study was to screen out the most effective compounds and evaluate the therapeutic efficacy. AB2, AB3 and AB10 demonstrated the lowest half-maximal inhibitory concentration (IC50) values in one metastatic follicular and two anaplastic thyroid cancer cell lines. Treatment with each of the three ABs resulted in an increase in apoptosis markers, including cleaved poly adenosine diphosphate ribose polymerase (PARP) and cleaved caspase 3. Additionally, the expression of cell-cycle regulatory proteins p21(WAF1) and p27(Kip1) increased with the treatment of ABs while cyclin D1 decreased. Furthermore, AB2, AB3 and AB10 were able to induce thyrocyte-specific genes in the three thyroid cancer cell lines indicated by increased expression levels of sodium iodide symporter, paired box gene 8, thyroid transcription factor 1 (TTF1), TTF2 and thyroid-stimulating hormone receptors. AB2, AB3 and AB10 suppress thyroid cancer cell growth via cell-cycle arrest and apoptosis. They also induce cell re-differentiation, which could make aggressive cancer cells more susceptible to radioactive iodine therapy.

Significant concentration changes of chemical components of PM1 in the Yangtze River Delta area of China and the implications for the formation mechanism of heavy haze-fog pollution.

Since the winter season of 2013, a number of persistent haze-fog events have occurred in central-eastern China. Continuous measurements of the chemical and physical properties of PM1 at a regional background station in the Yangtze River Delta area of China from 16 Nov. to 18 Dec., 2013 revealed several haze-fog events, among which a heavy haze-fog event occurred between 6 Dec. and 8 Dec. The mean concentration of PM1 was 212µgm(-3) in the heavy haze-fog period, which was about 10 times higher than on clean days and featured a peak mass concentration that reached 298µgm(-3). Organics were the largest contributor to the dramatic rise of PM1 on heavy haze-fog days (average mass concentration of 86µgm(-3)), followed by nitrate (58µgm(-3)), sulfate (35µgm(-3)), ammonium (29µgm(-3)), and chloride (4.0µgm(-3)). Nitrate exhibited the largest increase (~20 factors), associated with a significant increase in NOx. This was mainly attributable to increased coal combustion emissions, relative to motor vehicle emissions, and was caused by short-distance pollutant transport within surrounding areas. Low-volatility oxidized organic aerosols (OA) (LV-OOA) and biomass-burning OA (BBOA) also increased sharply on heavy haze-fog days, exhibiting an enhanced oxidation capacity of the atmosphere and increased emissions from biomass burning. The strengthening of the oxidation capacity during the heavy pollution episode, along with lower solar radiation, was probably due to increased biomass burning, which were important precursors of O3. The prevailing meteorological conditions, including low wind and high relative humidity, and short distance transported gaseous and particulate matter surrounding of the sampling site, coincided with the increased pollutant concentrations mainly from biomass-burning mentioned above to cause the persistent haze-fog event in the YRD area.

First Report of Streptomyces galilaeus Associated with Common Scab in China.

During a survey of potato scab pathogens in China from 2003 to 2012, a new pathogen was found in Shanxi and Neimenggu provinces. The incidence was approximately 20% of all recovered strains. The lesions caused by the pathogen were slightly raised and similar to those caused by Streptomyces scabies (3). Lesions were excised (approximately 10 mm3) from 40 infected tubers, surface-disinfested with 0.3% NaOCl for 30 s, rinsed in sterile water three times, cut into 5 mm3, then sliced into 1-mm pieces, and plated on water agar amended with ampicillin (50 µg/ml). Plates were incubated at 28°C in the dark for 4 days. The spores of Streptomyces sp. strains growing from the tuber pieces were collected from single bacterial colonies and cultured on oatmeal agar. To fulfill Koch's postulates, one strain, CPS-2, was grown at 28°C for 10 days and the spores were washed from the plates as inoculum. One hundred milliliters of inoculum (1 × 105 CFU/ml) was mixed with autoclaved soil and vermiculite (1:1) in each pot (15 cm in diameter). Cut tubers were planted in the pots (potato cv. Favorita, one plant per pot, five replicates) and grown under greenhouse conditions (22 ± 5°C). Typical common scab symptoms consisting of small, brown, raised lesions developed on potato tubers 12 weeks after planting. The same strain was re-isolated from the lesions of the new scabby tubers. Non-inoculated plants, treated as described above, but without strain CPS-2, remained healthy. The CPS-2 strain was identified based on morphological and physiological characterization and 16S rDNA sequence. On yeast-malt extract agar, the test strain produced grayish-white aerial hypha, reddish brown substrate mycelium and pigments, and loose spiral spore chains. Spores were smooth and were 0.8 to 0.9 × 1.1 to 1.2 µm in size (diameter and length). The ability of the strain to use single sources of carbon and nitrogen was verified according to the International Streptomyces project (4). The strain grew in media supplemented with L-arabinose, D-fructose, D-glucose, rhamnose, raffinose, meso-inositol, sucrose, and D-xylose, but not D-mannitol. It used L-hydroxyproline, L-methionine, and L-histidine, and produced melanin on tyrosine and peptone yeast extract agar. The strain did not grow at a pH less than 5.0 and was sensitive to streptomycin (20 µg/ml), phenol (0.1%), and crystal violet (0.5 µg/mL), but not to penicillin (10 IU/ml). The strain also produced hydrogen sulfide. The biological characteristics of strain CPS-2 were in accord with Streptomyces galilaeus. CPS-2 produced thaxtomin A in oatmeal liquid medium and the txt AB gene fragment was successfully amplified using specific primers (2). The 16S rDNA sequence of CPS-2 was amplified by PCR with primers 16S1-F: 5'-CATTCACGGAGAGTTTGATCC-3' and 16S1-R: 5'-AGAAAGGAGGTGATCCAGCC-3' (1) and sequenced. A BLAST search of the 16S rDNA sequence for CPS-2 was conducted using the NCBI GenBank database, resulting in 99.8% similarity to S. galilaeus (NR_040857). The 16S rDNA sequence for CPS-2 (1,388 bp) was deposited in GenBank (AY621378). To our knowledge, this is the first report of S. galilaeus causing common scab of potato in China. References: (1) R. A. Bukhalid et al. Appl. Environ. Microbiol. 68:738, 2002. (2) R. Flores-González et al. Plant Pathol. 57:162, 2008. (3) D. H. Lambert and R. Loria. Int. J. Syst. Bacteriol. 39:387, 1989. (4) E. B. Shirling and D. Gottlieb. Int. J. Syst. Bacteriol. 16:313, 1966.