[Clinical efficacy of induction chemoimmunotherapy for locally advanced hypopharyngeal carcinoma: a prospective phase â ¡ study].

Objective: To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR. Methods: A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m2 day 1, cisplatin 25 mg/m2 days 1-3, and capecitabine 800 mg/m2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results: A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm3. The T stage (OR=12.71, 95%CI: 1.4-112.5, P=0.022) and the volume (OR=7.1, 95%CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion: The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.

[Shenqi Wenfei Formula alleviates chronic obstructive pulmonary disease in rats with pulmonary qi deficiency syndrome by regulating NLRP3/GSDMD pyroptosis pathway].

OBJECTIVE: To investigate the effects of Shenqi Wenfei (SQWF) Formula on the NLRP3/GSDMD signaling pathway in pulmonary qi deficiency syndrome rats with chronic obstructive pulmonary diseases (COPD). METHODS: Rat models of COPD and lung qi deficiency syndrome induced by exposure to cigarette smoke and lipopolysaccharide (LPS) injection were randomized (n=8) for treatment with low-, medium- and high-dose SQWF or Yu Ping Feng (YPF). The changes in body weight, grip strength, lung function, pulmonary pathology, peripheral blood inflammatory cell counts, and levels of inflammatory factors in the bronchoalveolar lavage fluid (BALF) were examined. The expressions of proteins associated with the NLRP3/GSDMD signaling pathway in the lung tissues were determined with RT-qPCR and immunohistochemistry. RESULTS: The rat models of COPD and lung qi deficiency syndrome showed significantly reduced body weight, grip strength and lung function (P<0.01) with severe lung pathologies, increased levels of WBC, NEU% and MON% (P<0.01), decreased LYM% (P<0.01), and increased levels of TNF-α, IL-6, IL-1ß and IL-18 in the BALF (P<0.01); the mRNA and protein expression levels of NLRP3, ASC, GSDMD and IL-1ß all increased significantly in the lung tissue (P<0.01). Treatment with SQWF and YPF obviously increased body weight and improved grip strength, pulmonary function and lung pathology of the COPD rats (P<0.05). The treatments obviously improved the changes in peripheral blood inflammatory cell counts and inflammatory factors in the BALF of the rat models (P<0.01) and lowered the expressions of NLRP3, ASC, GSDMD and IL-1ß in the lung tissues (P<0.05) without significantly affecting the mRNA levels of caspase-1 and IL-18 (P>0.05), and the effects of SQWF were dose-dependent. CONCLUSION: SQWF Formula relieves inflammatory response and injury in the lung tissue of COPD rats with pulmonary qi deficiency syndrome possibly by inhibiting pyroptosis through regulating the NLRP3/GSDMD pathway.

Methionine supplementation during a hydrogen peroxide challenge alters components of insulin signaling and antioxidant proteins in subcutaneous adipose explants from dairy cows.

Enhanced postruminal supply of methionine (Met) during the peripartal period alters protein abundance of insulin, AA, and antioxidant signaling pathways in subcutaneous adipose tissue (SAT). Whether SAT is directly responsive to supply of Met and can induce molecular alterations is unknown. Our objective was to examine whether enhanced Met supply during an oxidative stress challenge in vitro alters insulin, AA, inflammation, and antioxidant signaling-related protein networks. Four late-lactation Holstein cows (average 27.0 kg of milk per day) were used for SAT collection. Tissue was incubated in duplicate for 4 h in a humidified incubator with 5% CO2 at 37°C according to the following experimental design: control medium with an "ideal" profile of essential AA (CTR; Lys:Met 2.9:1), CTR plus 100 µM H2O2 (HP), or CTR with greater Met supply plus 100 µM H2O2 (HPMET; Lys:Met 2.5:1). Molecular targets associated with insulin signaling, lipolysis, antioxidant nuclear factor, erythroid 2 like 2 (NFE2L2), inflammation, and AA metabolism were determined through reverse-transcription quantitative PCR and western blotting. Data were analyzed using the MIXED procedure of SAS 9.4 (SAS Institute Inc.). Among proteins associated with insulin signaling, compared with CTR, HP led to lower abundance of phosphorylated AKT serine/threonine kinase (p-AKT) and solute carrier family 2 member 4 (SLC2A4; insulin-induced glucose transporter). Although incubation with HPMET restored abundance of SLC2A4 to levels in the CTR and upregulated abundance of fatty acid synthase (FASN) and phosphorylated 5'-prime-AMP-activated protein kinase (p-AMPK), it did not alter p-AKT, which remained similar to HP. Among proteins associated with AA signaling, compared with CTR, challenge with HP led to lower abundance of phosphorylated mechanistic target of rapamycin (p-MTOR), and HPMET did not restore abundance to CTR levels. Among inflammation-related targets studied, incubation with HPMET led to greater protein abundance of nuclear factor kappa B subunit p65 (NFKB-RELA). The response in NFKB observed with HPMET was associated with a marked upregulation of the antioxidant transcription regulator NFE2L2 and the antioxidant enzyme glutathione peroxidase 1 (GPX1). No effects of treatment were detected for mRNA abundance of proinflammatory cytokines or antioxidant enzymes, underscoring the importance of post-transcriptional regulation. Overall, data indicated that short-term challenge with H2O2 was particularly effective in reducing insulin and AA signaling. Although a greater supply of Met had little effect on those pathways, it seemed to restore the protein abundance of the insulin-induced glucose transporter. Overall, the concomitant upregulation of key inflammation and antioxidant signaling proteins when a greater level of Met was supplemented to oxidant-challenged SAT highlighted the potential role of this AA in regulating the inflammatory response and oxidant status. Further studies should be conducted to assess the role of postruminal supply of Met and other AA in the regulation of immune, antioxidant, and metabolic systems in peripartal cow adipose tissue.

Quantitative comparative phosphoproteomic analysis of the effects of colostrum and milk feeding on liver tissue of neonatal calves.

Posttranslational modifications, mostly phosphorylation, are critical for protein structure and function. However, the association between liver phosphoproteins in neonatal calves and colostrum intake is not well understood. In this study, we examined the liver phosphoproteome profile in neonatal calves after receiving colostrum or milk. Liver tissue samples were collected from control calves (CON, n = 3) 2 h after birth and from calves that received colostrum (CG, n = 3) or milk (MG, n = 3) 24 h after birth. Hepatic phosphoprotein expression profiles were analyzed using quantitative proteomics based on the liquid chromatography-tandem mass spectrometry method. In total, 1,587 phosphorylated sites were identified in 1,011 liver proteins. The most abundant phosphorylation site AA was serine (87.5%), followed by threonine (11.9%) and tyrosine (0.5%). Among the 1,011 phosphoproteins, 219, 453, and 26 displayed differential expression in the CG versus MG, CG versus CON, and MG versus CON comparisons, respectively. Differentially expressed phosphoproteins in the CG-MG comparison included 3-phosphoinositide-dependent protein kinase 1, glucose transporter member 4, protein kinase N2, and vinculin, which were mainly involved in the glycogen metabolic process, transport, growth and development, and cell adhesion process, according to Gene Ontology analysis. Pathway analysis indicated their enrichment in the insulin signaling pathway, spliceosome, and adherens junction. The CG-CON comparison identified differentially expressed phosphoproteins and their target genes that were largely involved in the cellular process, macromolecule metabolic process, developmental process, and transport. Pathway analysis indicated their association with endocytosis, mechanistic target of rapamycin, AMP-activated protein kinase, and insulin signaling pathways. These data demonstrate that changes in the phosphoproteins of liver tissues may play an important role in energy metabolism and immune response in the calves that received colostrum. These results provide novel insights into the crucial roles of protein phosphorylation during the early life of newborn calves.

Effects of non-drug interventions on depression, anxiety and sleep in COVID-19 patients: a systematic review and meta-analysis.

OBJECTIVE: Patients with Coronavirus Disease 2019 (COVID-19) suffer from anxiety, depression and sleep disorders due to isolation treatment, among other reasons. Whether non-drug interventions can be alternative therapies for COVID-19 patients with anxiety, depression and sleep disorders is controversial. Therefore, we conducted a meta-analysis and systematic review to evaluate the effects of non-drug interventions on anxiety, depression and sleep in patients with COVID-19 to provide guidance for clinical application. MATERIALS AND METHODS: We searched the following databases for randomized controlled trials (RCTs) from December 2019 to July 2020: China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chongqing VIP Chinese Science and Technology Periodical Database (VIP), Wanfang, Cochrane Library, Web of Science, PubMed, MEDLINE and Embase. Two investigators independently screened the literature according to the inclusion and exclusion criteria, extracted data and evaluated the risk of bias in the included studies. Meta-analysis was performed using RevMan5.3 software. RESULTS: A total of 5 articles with 768 subjects were included. Meta-analysis results indicated that non-drug interventions can reduce anxiety [SMD=-1.40, 95% CI (-1.62, -1.17), p<0.00001] and depression [SMD=-1.22, 95% CI (-2.01, -0.43), p=0.002] scores in patients with COVID-19. Descriptive analysis indicated that non-drug interventions can improve the sleep status of COVID-19 patients. Sensitivity analysis indicated that the meta-analysis results were stable. Egger's test and Begg's test showed no publication bias. CONCLUSIONS: This meta-analysis found that non-drug interventions can reduce the anxiety and depression scores of patients with COVID-19. Due to the limitations of this study, more high-quality studies are needed to verify the findings, especially the effect of non-drug interventions on improving the sleep status of COVID-19 patients.

Dietary supplementation with Bacillus subtilis DSM 32315 alters the intestinal microbiota and metabolites in weaned piglets.

AIM: The study was conducted to investigate the effects of dietary Bacillus subtilis (BS) DSM 32315 on the intestinal microbiota composition and metabolites of weaned pigs. METHODS AND RESULTS: Sixty-four piglets were allocated to two groups (control and BS), each group including eight replicates with four piglets. Dietary BS DSM 32315 increased (P < 0·05) the abundances of jejunal Leucobacter and Cupriavidus, ileal Thermus, Coprococcus and Bifidobacterium, as well as colonic Succiniclasticum; and increased the concentrations of ileal straight-chain fatty acids, colonic propionate, branched-chain fatty acids (BCFAs), and tyramine, but decreased (P < .05) the colonic indole concentration. The ileal and colonic microbial community structure tended to cluster into two groups. LEfSe analysis identified five microbial biomarkers in jejunum and eight biomarkers in ileum in the BS group, and three biomarkers in colon in the control group. The ileal Bifidobacterium abundance was positively correlated (P < 0·05) with isovalerate concentration, while the colonic Actinobacteria and Lactobacillus abundances were negatively correlated (P < 0·05) with indole concentration. CONCLUSION: These findings suggest that dietary supplementation with BS DSM 32315 could alter the diversity, composition, and metabolites of intestinal microbiota in weaned piglets. SIGNIFICANCE AND IMPACT OF THE STUDY: Weaned piglets are often accompanied with impaired gastrointestinal tract and intestinal disorder affecting their growth. This study demonstrated that dietary BS DSM 32315 presented a beneficial role in gut health via regulating intestinal microbiota composition and metabolites.

[Establishment and gene expression analysis of drug-resistant cell lines in hepatocellular carcinoma induced by sorafenib].

OBJECTIVE: To establish the drug-resistant cell lines of hepatocellular carcinoma (HCC) induced by sorafenib, and to screen out the high expression genes in drug-resistant cell lines of HCC induced by sorafenib, then to explore the genes related to sorafenib resistance in hepatocellular carcinoma. METHODS: The human PLC and Huh7 cell lines were obtained, then the PLC and Huh7 drug-resistant cell lines were induced with sorafenib by using intermittent induction in vitro. CCK8 assay was used to detect the IC50 value of sorafenib for evaluation of drug sensitivity of hepatocellular carcinoma cell lines in PLC and Huh7. All the up regulated genes in PLC and Huh7 drug-resistant cell lines induced by sorafenib were screened out using high-throughput cDNA sequencing (RNA-Seq), Ualcan database was used to analyze the correlations between the up regulated genes in PLC and Huh7 drug-resistant cell lines induced and four clinical biological characteristics of hepatocellular carcinoma, including the gene expressions between normal samples and tumor samples, tumor stage, tumor grade, and patient overall survival, to find the genes that might be involved in the mechanism of sorafenib resistance of hepatocellular carcinoma. RESULTS: All the up regulated genes detected by the using high-throughput cDNA sequencing (RNA-Seq) in PLC and Huh7 drug-resistant cell lines were further screened out by following conditions:(1) genes co-expressed in PLC and Huh7 drug-resistant cells induced by sorafenib, (2) the fold change was more than 4 times and the difference was statistically significant (P <0.05), the top 12 up regulated genes in PLC and Huh7 drug-resistant cell lines were found, which were TPSG1, CBX4, CLC, CLEC18C, LGI4, F2RL1, S100A6, HABP2, C15ORF48, ZG16, FOLH1, and EPCAM. Compared with the correlations between the twelve genes and the clinical biological characteristics by Ualcan database, the potentially significant gene CBX4 was screened out. CONCLUSION: The human PLC and Huh7 drug-resistant cell lines of hepatocellular carcinoma induced by sorafenib were successfully established. CBX4, the gene related to sorafenib resistance in hepatocellular carcinoma, was screened out by the high-throughput cDNA sequencing (RNA-Seq) and further analysis using Ualcan database, which is providing a powerful basis for further research on the mechanism of sorafenib resistance of hepatocellular carcinoma.

[Granulomatous lobular mastitis: a clinicopathological analysis of 300 cases].

Objective: To investigate the clinicopathologic features and possible causes of granulomatous lobular mastitis(GLM). Methods: Three hundred cases of GLM were collected from surgical specimens diagnosed at Longhua Hospital, Shanghai University of Traditional Chinese Medicine from January 2015 to November 2017. Morphologic features were reviewed using HE staining. A total of 116 cases were investigated by Gram staining. The expression of CD3, CD20, CD68, IgG, IgG4, CD38 and CD138 was detected by immunohistochemical staining. Results: The age of the patients was 23 to 47 years and the median age was 32 years. All patients were female, 96.7% (290/300) had a history of lactation.There were 143 cases of left breasts, 138 cases of right breast and 19 cases of bilateral breasts. Serum prolactin increased in 39.7%(119/300) patients. Within 15.7%(47/300) of patients were associated with nodular erythema or joint swelling and pain of the lower extremities. Pathological observation showed that lobular-centric suppurative granulomatous inflammation, accompanied by dilatation of intralobular and interlobular ducts. There were 16 cases accompanied with duct ectasia. Immunohistochemistry showed CD3-positive lymphocytes were more than CD20-positive lymphocytes in the peripheral aggregation zone of neutrophils within granulomatous lesions. Gram positive bacteria were found in the lipid vacuoles of the 51.7%(60/116) patients. Conclusions: GLM has distinctive histologic features. It may be related to corynebacterium infection, or accompanied by the increase of serum prolactin and erythrocyte sedimentation rate. The age, location and history of the disease are importance in the diagnosis and differential diagnosis.

Observation of three-component fermions in the topological semimetal molybdenum phosphide.

In quantum field theory, Lorentz invariance leads to three types of fermion-Dirac, Weyl and Majorana. Although the existence of Weyl and Majorana fermions as elementary particles in high-energy physics is debated, all three types of fermion have been proposed to exist as low-energy, long-wavelength quasiparticle excitations in condensed-matter systems. The existence of Dirac and Weyl fermions in condensed-matter systems has been confirmed experimentally, and that of Majorana fermions is supported by various experiments. However, in condensed-matter systems, fermions in crystals are constrained by the symmetries of the 230 crystal space groups rather than by Lorentz invariance, giving rise to the possibility of finding other types of fermionic excitation that have no counterparts in high-energy physics. Here we use angle-resolved photoemission spectroscopy to demonstrate the existence of a triply degenerate point in the electronic structure of crystalline molybdenum phosphide. Quasiparticle excitations near a triply degenerate point are three-component fermions, beyond the conventional Dirac-Weyl-Majorana classification, which attributes Dirac and Weyl fermions to four- and two-fold degenerate points, respectively. We also observe pairs of Weyl points in the bulk electronic structure of the crystal that coexist with the three-component fermions. This material thus represents a platform for studying the interplay between different types of fermions. Our experimental discovery opens up a way of exploring the new physics of unconventional fermions in condensed-matter systems.

Anticoccidial evaluation of a traditional Chinese medicine--Brucea javanica--in broilers.

The traditional Chinese medicinal plant Brucea javanica has received much attention for its significant antiprotozoal effects in recent years; however, little is known about its potential anticoccidial functions. In the present study, a series of experiments was conducted to investigate the prophylactic and therapeutic effects of ethanol extract from B. javanica on coccidiosis induced by Eimeria tenella in broiler chickens. Chickens infected with E. tenella were treated with B. javanica extract and compared either with broilers treated with the anticoccidial halofuginone hydrobromide (Stenorol) or with control groups that consisted of infected-unmedicated and uninfected-unmedicated broilers. The experiments revealed that the B. javanica extract could significantly (P<0.05) reduce bloody diarrhea and lesion scores. Additional, OPG output in these plant extract treated groups was reduced in comparison with non-treated groups (P<0.05). However, there was no evidence to show that the extract could promote BWG. Histological data showed that the number of second-generation schizonts in the medicated groups was substantially less than that in the infected-unmedicated control. In summary, our work showed that B. javanica extract exerted considerable anticoccidial effects, supporting its use as a promising therapeutic in controlling avian coccidiosis.

Pharmacokinetics and ex-vivo pharmacodynamics of cefquinome against Klebsiella pneumonia in healthy dogs.

A two-period cross-over study was carried to investigate the pharmacokinetics (PK) and ex-vivo pharmacodynamics (PD) of cefquinome when administrated intravenously (IV) and intramuscularly (IM) in seven healthy dogs at a dose of 2 mg/kg of body weight. Serum concentrations were determined by HPLC-MS/MS assay and cefquinome concentration vs. time data after IV and IM were best fit to a two-compartment open model. Cefquinome mean values of area under concentration-time curve (AUC) were 5.15 µg · h/mL for IV dose and 4.59 µg · h/mL for IM dose. Distribution half-lives and elimination half-lives after IV dose and IM dose were 0.27 and 0.44 h, 1.53 and 1.94 h, respectively. Values of total body clearance (ClB ) and volume of distribution at steady-state (Vss ) were 0.49 L · kg/h and 0.81 L/kg, respectively. After IM dose, Cmax was 2.53 µg/mL and the bioavailability was 89.13%. For PD profile, the determined MIC and MBC values against K. pneumonia were 0.030 and 0.060 µg/mL in MHB and 0.032 and 0.064 µg/mL in serum. The ex vivo time-kill curves also were established in serum. In conjunction with the data on MIC, MBC values and the ex vivo bactericidal activity in serum, the present results allowed prediction that a single cefquinome dosage of 2 mg/kg may be effective in dogs against K. pneumonia infection.

Different reactions of potato varieties to infection by potato leafroll virus, and associated responses by its vector, Myzus persicae (Sulzer).

Vector-dependent plant pathogens can alter their hosts such that vector behavior and pathogen spread are affected. For example, Potato leafroll virus (PLRV)-induces changes in volatiles emitted by potato plants (Solanum tuberosum L.) that influence settling behavior by Myzus persicae, a principal vector of the virus. Prior work in this pathosystem has utilized a single potato variety, Russet Burbank, but as is true for other plant responses to biotic stresses, responses may differ among plant genotypes. To examine this, PLRV-induced changes in headspace volatile organic compounds (VOCs) and associated aphid responses to these VOCs were compared among four potato varieties (Chipeta, Desiree, IdaRose, and Russet Burbank). Total headspace VOCs differed among the varieties and were differentially induced by PLRV infection such that the effect of variety, infection, and their interaction was significant; two of the varieties had increased concentrations of headspace VOCs, and two did not. MANOVA for the effect of infection and variety on total VOCs and major VOC classes also was significant. A principal component analysis (PCA) partially separated the VOC profiles from the four varieties. Aphid arrestment differed in response to the VOCs of the four varieties, and was greater on those that were more readily infected by PLRV (Desiree and Russet Burbank) as compared with those that were less readily infected (Chipeta and IdaRose). Aphid responses were not clearly related to specific characteristics of blends, such that total VOCs and composition appear to contribute. The four varieties used in this study have distinct pedigrees representative of different cultivated forms of S. tuberosum. Although cultivated potato varieties have been subjected to genetic manipulation by humans, the differences in PLRV induced changes in VOCs nonetheless indicate the potential for complex effects of PLRV infection on host plant VOC emissions, and vector responses in managed, and natural systems.

Do probiotics improve eradication response to Helicobacter pylori on standard triple or sequential therapy?

BACKGROUND: The standard triple therapy for the eradication of Helicobacter pylori consists of a combination of a proton pump inhibitor at a standard dose together with two antibiotics (amoxicillin 1000 mg plus either clarithromycin 500 mg or metronidazole 400 mg) all given twice daily for a period of 7-14 days. Recent reports have shown a dramatic decline in the rate of H. pylori eradication utilizing standard triple therapy from 95% down to 70-80%. AIMS: Our study was designed to evaluate the effect of adding a probiotic as an adjuvant to common regimens used for H. pylori eradication. MATERIALS AND METHODS: An open label randomized observational clinical study was designed to test three different regimens of H. pylori eradication treatment: Standard triple therapy with a concomitant probiotic added at the same time (n = 100), starting the probiotic for 2 weeks before initiating standard triple therapy along with the probiotic (n = 95), and the third regimen consists of the probiotic given concomitantly to sequential treatment (n = 76). The three arms were compared to a control group of patients treated with the traditional standard triple therapy (n = 106). RESULTS: The eradication rate for the traditional standard therapy was 68.9%, and adding the probiotic "Bifidus infantis" to triple therapy, led to a successful rate of eradication of 83% (P < 0.001). Pre-treatment with 2 weeks of B. infantis before adding it to standard triple therapy increased the success rate of eradication to 90.5%. Similar improvement in eradication rate was noted when B. infantis was added as an adjuvant to the sequential therapy leading to an eradication rate of 90.8%. CONCLUSION: Adding B. infantis as an adjuvant to several therapeutic regimens commonly used for the eradication of H. pylori infection significantly improves the cure rates.

Unconventional anisotropic s-wave superconducting gaps of the LiFeAs iron-pnictide superconductor.

We have performed high-resolution angle-resolved photoemission spectroscopy on Fe-based superconductor LiFeAs (T(c)=18 K). We reveal multiple nodeless superconducting (SC) gaps with 2Δ/k(B)T(c) ratios varying from 2.8 to 6.4, depending on the Fermi surface (FS). We also succeeded in directly observing a gap anisotropy along the FS with magnitude up to ~30%. The anisotropy is fourfold symmetric with an antiphase between the hole and electron FSs, suggesting complex anisotropic interactions for the SC pairing. The observed momentum dependence of the SC gap offers an excellent opportunity to investigate the underlying pairing mechanism.

Fermi surface nesting induced strong pairing in iron-based superconductors.

The discovery of high-temperature superconductivity in iron pnictides raised the possibility of an unconventional superconducting mechanism in multiband materials. The observation of Fermi-surface (FS)-dependent nodeless superconducting gaps suggested that inter-FS interactions may play a crucial role in superconducting pairing. In the optimally hole-doped Ba(0.6)K(0.4)Fe(2)As(2), the pairing strength is enhanced simultaneously (2Delta/T(c) approximately 7) on the nearly nested FS pockets, i.e., the inner hole-like (alpha) FS and the 2 hybridized electron-like FSs, whereas the pairing remains weak (2Delta/T(c) approximately 3.6) in the poorly nested outer hole-like (beta) FS. Here, we report that in the electron-doped BaFe(1.85)Co(0.15)As(2), the FS nesting condition switches from the alpha to the beta FS due to the opposite size changes for hole- and electron-like FSs upon electron doping. The strong pairing strength (2Delta/T(c) approximately 6) is also found to switch to the nested beta FS, indicating an intimate connection between FS nesting and superconducting pairing, and strongly supporting the inter-FS pairing mechanism in the iron-based superconductors.

Cytotoxic benzo[j]fluoranthene metabolites from Hypoxylon truncatum IFB-18, an endophyte of Artemisia annua.

Two new benzo[j]fluoranthene-based secondary metabolites named daldinone C (1) and daldinone D (2), along with two known metabolites, altechromone A and (4S)-5,8-dihydroxy-4-methoxy-alpha-tetralone, were isolated from the CHCl3/MeOH (1:1) extract of a solid culture of the endophyte Hypoxylon truncatum IFB-18 harbored inside the symptomless stem tissue of Artemisia annua. The structures of the new compounds were elucidated by MS and 1D and 2D NMR spectra and by X-ray diffraction analysis. Their absolute configurations were determined unambiguously by a combination of their CD data and the established exciton chirality rule. Compounds 1 and 2 were substantially cytotoxic against SW1116 cells, with IC50 values of 49.5 and 41.0 microM, respectively, comparable to that (37.0 microM) of 5-fluorouracil. The biosynthetic pathway for 1 and 2 was postulated with the natural occurrence of benzo[j]fluoranthene analogues discussed in brief.

Diagnostic value of protein induced by vitamin K absence (PIVKAII) and hepatoma-specific band of serum gamma-glutamyl transferase (GGTII) as hepatocellular carcinoma markers complementary to alpha-fetoprotein.

Serum protein induced by vitamin K absence or antagonist II (PIVKAII), hepatoma-specific band of serum gamma-glutamyl transferase (GGTII), and alpha-fetoprotein (AFP) levels were determined in 120 patients with hepatocellular carcinoma (HCC) and 90 patients with cirrhosis. The mean serum concentration of PIVKAII in HCC patients was higher than that in cirrhotic patients. A total of 53.3% of patients (64 out of 120) with HCC had PIVKAII levels above 40 mAU ml(-1). However, only 13 patients with cirrhosis had higher PIVKA II levels. Of 32 small HCC patients, 13 (40.6%) had PIVKAII values above 40 mAU ml(-1). An increased concentration of AFP (i.e. 20 ng ml(-1)) was observed in 70 out of 120 (58.3%) patients with HCC and in 33 out of 90 (36.7%) patients with cirrhosis. Positive GGTII was found in 74.0% (89 out of 120) cases of HCC (sensitivity), in 16 of 90 cases of cirrhosis, and 14 of 32 (43.8%) small HCC patients had GGTII positive. No significant correlation was found between serum levels of AFP and PIVKAII. Combining the information from PIVKAII, AFP, and GGTII significantly increases the sensitivity over AFP alone. PIVKAII and GGTII are useful tumour markers complementary to AFP for diagnosis of HCC.

Two new fatty diterpenoids from Salvia miltiorrhiza.

Two new fatty abietane diterpenoids, oleoyl neocryptotanshinone (1) and oleoyl danshenxinkun A (2), were isolated as minor components from the roots of Salvia miltiorrhiza. Their structures were established on the basis of spectral evidence. In preliminary tests, they selectively inhibited rabbit platelet aggregation induced by arachidonic acid.

Aggregation inhibitory activity of minor acetophenones from Paeonia species.

Two minor acetophenones, 2,5-dihydroxy-4-methoxy-acetophenone (2) and 2,5-dihydroxy-4-methylacetophenone (7) from Paeonia species were found to selectively inhibit the aggregation of rabbit platelets induced by arachidonic acid. They were more potent than the major compound, paeonol (1), and 7 also inhibited the formation of TXA2 and PGD2 from arachidonic acid.