Identification and validation of tumor-specific T cell receptors from tumor infiltrating lymphocytes using tumor organoid co-cultures.

T cell receptor-engineered T cells (TCR-Ts) therapy is promising for cancer immunotherapy. Most studies have focused on identifying tumor-specific T cell receptors (TCRs) through predicted tumor neoantigens. However, current algorithms for predicting tumor neoantigens are unreliable and many neoantigens are derived from non-coding regions. Thus, the technological platform for identifying tumor-specific TCRs using natural antigens expressed on tumor cells is urgently needed. In this study, tumor organoids-enriched tumor infiltrating lymphocytes (oeT) were obtained by repeatedly stimulation of autologous patient-derived organoids (PDO) in vitro. The oeT cells specifically responded to autologous tumor PDO by detecting CD137 expression and the secretion of IFN-γ using enzyme-linked immunospot assay. The measurement of oeT cell-mediated killing of three-dimensional organoids was conducted using a caspase3/7 flow cytometry assay kit. Subsequently, tumor-specific T cells were isolated based on CD137 expression and their TCRs were identified through single-cell RT-PCR analysis. The specificity cytotoxicity of TCRs were confirmed by transferring to primary peripheral blood T cells. The co-culture system proved highly effective in generating CD8+ tumor-specific oeT cells. These oeT cells effectively induced IFN-γ secretion and exhibited specificity in killing autologous tumor organoids, while not eliciting a cytotoxic response against normal organoids. The analysis conducted by TCRs revealed a significant expansion of T cells within a specific subset of TCRs. Subsequently, the TCRs were cloned and transferred to peripheral blood T cells generation engineered TCR-Ts, which adequately recognized and killed tumor cell in a patient-specific manner. The co-culture system provided an approach to generate tumor-specific TCRs from tumor-infiltrating lymphocytes of patients with colorectal cancer, and tumor-specific TCRs can potentially be used for personalized TCR-T therapy.

Immune landscape of viral cancers: Insights from single-cell sequencing.

Viral infections trigger a wide range of immune responses thought to drive tumorigenesis and malignant progression. Dissecting virus-induced changes in the tumor immune microenvironment (TIME) is therefore crucial to identify key leukocyte populations that may represent novel targets for cancer therapy. Single-cell sequencing approaches have now been widely applied to the analysis of various tumors, thus enabling multiomics characterization of the highly heterogeneous TIME that bulk-sequencing cannot fully elucidate. In this review, we summarized key recent findings from sequencing studies of the immune infiltrate and antitumor response in virus-associated cancers at single cell resolution. Additionally, we also reviewed recent developments in immunotherapy for virus-associated cancers. We anticipate that the strategic use of single-cell sequencing will advance our understanding of the TIME of viral cancers, leading to the development of more potent novel treatments.

Nitrogen-doped graphene quantum dots prepared by electrolysis of nitrogen-doped nanomesh graphene for the fluorometric determination of ferric ions.

Nitrogen-doped graphene quantum dots (N-GQDs) were synthesized by direct electrolysis of a carbon cloth electrode coated with nitrogen-doped nanomesh graphene (NG) in high yield (~ 25%). The N-GQDs emit intense blue fluorescence with a quantum yield (QY) of 10% ± 3%. Meanwhile, the N-GQDs are rich in hydroxyl, carboxyl, basic pyridinic nitrogen, and nitro groups, which are conducive to strengthen the interaction between N-GQDs and Fe3+ for highly sensitive determination of Fe3+ ions. Specifically, the determination for Fe3+ was conducted at different concentrations of N-GQD solution with a wide linear range of 10-1000 µM (150 µg·mL-1) and a low detection limit of 0.19 µM (10 µg·mL-1). Moreover, the fluorescence quenching mechanism illustrated that the functional groups generated by electrochemical oxidation enhanced the interaction of N-GQDs and Fe3+, and the narrow band gap (2.83 eV) of N-GQDs accomplished electron transfer from N-GQDs to Fe3+ easily. Graphical abstract A highly conductive carbon cloth electrode coated with nitrogen-doped nanomesh graphene (NG) was developed to prepared nitrogen-doped graphene quantum dots (N-GQDs) which was endowed with a wide linear range from 10 to 1000 µM (150 µg/mL) and a low detection limit of 0.19 µM (10 µg/mL) in the determination of Fe3+.

Characterization, evolution and functional analysis of the liver-expressed antimicrobial peptide 2 (LEAP-2) gene in miiuy croaker.

As an evolutionarily older defense strategy, the innate immune is the dominant immune system and provides a first line of antimicrobial host defense in teleost. Liver-expressed antimicrobial peptide-2 (LEAP-2) is a critical molecule of the innate immune system and plays a very important role in resistance against bacterial infections. We reported comprehensive analysis and characterization of LEAP-2 gene from miiuy croaker (Miichthys miiuy) in here. The complete cDNA of miiuy croaker LEAP-2 consists 2360 bp, including a 5' terminal untranslated region (UTR) of 170 bp, an open reading frame (ORF) of 312 bp, and a 3'-UTR of 1878 bp. Interestingly, two polyadenylation signals (AATTAAA) which may involve the stability, translation efficiency, or localization of an mRNA in a tissue were found in 3'-UTR. Genomic DNA of miiuy croaker LEAP-2 includes three exons and two introns, which is similar to LEAP-2 genes in other mammals and fish. The deduced 103 amino acids consist of signal peptide, prodomain and mature peptide. Four highly conserved cysteine residues involved two disulfide bridges in mature peptide. Real-time PCR results showed that LEAP-2 was ubiquitously expressed in all tissues and the expression level was highest in liver. Significantly, the expression levels were increased after infection with Vibrio anguillarum in liver and spleen. The antimicrobial activity analysis result of LEAP-2 in vitro indicated that LEAP-2 of miiuy croaker was effective in controlling Aeromonas hydrophila. In addition, we performed evolutionary analysis in order to estimate the selective constraints on the LEAP-2 gene. The result indicated that no positive selection exists in LEAP-2 gene sequences, which may be on account of irreplaceable function constrains. Meanwhile, we compared the structure of LEAP-2 with that of another Liver-expressed antimicrobial peptide (LEAP-1, also named HAMP), and found the LEAP-2 from miiuy croaker comprises of α-helix, ß-sheet, and ß-turn while the LEAP-1 of miiuy croaker only contains ß-sheet.

A PKS I gene-based screening approach for the discovery of a new polyketide from Penicillium citrinum Salicorn 46.

Salicorn 46, an endophytic fungus isolated from Salicornia herbacea Torr., was identified as Penicillium citrinum based on its internal transcribed spacer and ribosomal large-subunit DNA sequences using a type I polyketide synthase (PKS I) gene screening approach. A new polyketide, penicitriketo (1), and seven known compounds, including ergone (2), (3ß,5α,8α,22E)-5,8-epidioxyergosta-6,9,22-trien-3-ol (3), (3ß,5α,8α,22E)-5,8-epidioxyergosta-6,22-dien-3-ol (4), stigmasta-7,22-diene-3ß,5α,6α-triol (5), 3ß,5α-dihydroxy-(22E,24R)-ergosta-7,22-dien-6ß-yl oleate (6), N b-acetyltryptamine (7), and 2-(1-oxo-2-hydroxyethyl) furan (8), were isolated from the culture of Salicorn 46, and their chemical structures were elucidated by spectroscopic analysis. Antioxidant experiments revealed that compound 1 possessed moderate DPPH radical scavenging activity with an IC50 value of 85.33 ± 1.61 µM. Antimicrobial assays revealed that compound 2 exhibited broad-spectrum antimicrobial activity against Candida albicans, Clostridium perfringens, Mycobacterium smegmatis, and Mycobacterium phlei with minimal inhibitory concentration (MIC) values of 25.5, 25.5, 18.5, and 51.0 µM, respectively. Compound 3 displayed potent antimicrobial activities against C. perfringens and Micrococcus tetragenus with a MIC value of 23.5 µM. Compounds 5 and 6 showed high levels of selectivity toward Bacillus subtilis and M. phlei with MIC values of 22.5 and 14.4 µM, respectively. The results of this study highlight the use of PCR-based techniques for the screening of new polyketides from endophytic fungi containing PKS I genes.

Pharmacokinetics, pharmacodynamics, and safety of asundexian in healthy Chinese and Japanese volunteers, and comparison with Caucasian data.

There is an unmet clinical need for effective anticoagulant therapies for the management of thromboembolic diseases that are not associated with a relevant risk of bleeding. Asundexian (BAY 2433334) is an oral, direct, small-molecule inhibitor of activated factor XI (FXIa). Phase I data from healthy Caucasian male participants indicated predictable pharmacokinetic (PK) and pharmacodynamic (PD) profiles and no clinically relevant bleeding-related adverse events (AEs). Reported here are data from two phase I, randomized, placebo-controlled, single- and multiple-dose escalation studies of asundexian conducted in 60 healthy men: 24 Japanese and 36 Chinese. Baseline characteristics were comparable between the treatment groups. All treatment-emergent AEs were mild, with no serious AEs or AEs of special interest reported. Systemic exposure to asundexian increased dose proportionally after single or multiple dosing, with relatively low accumulation following multiple once-daily dosing in both Chinese and Japanese volunteers. Asundexian induced dose-dependent prolongation of activated partial thromboplastin time and inhibition of FXIa activity, with no effects on prothrombin time or FXI concentration in Japanese participants. There were no clinically relevant interethnic differences in PK profile across the Japanese, Chinese, and Caucasian (data from the previous phase I study) participants and no clinically relevant difference in PD response between Japanese and Caucasian participants.

Pharmacokinetics, pharmacodynamics, and safety of fesomersen, a novel antisense inhibitor of factor XI, in healthy Chinese, Japanese, and Caucasian volunteers.

The inhibition of coagulation factor XI (FXI) presents an attractive approach for anticoagulation as it is not expected to increase the risk of clinically relevant bleeding and is anticipated to be at least as effective as currently available anticoagulants. Fesomersen is a conjugated antisense oligonucleotide that selectively inhibits the expression of FXI. The article describes three clinical studies that investigated the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of fesomersen after subcutaneous (s.c.) injection to healthy participants. The studies included participants from diverse ethnic backgrounds (Caucasian, Japanese, and Chinese). Fesomersen demonstrated good safety and tolerability in all three studies. No major bleeding events were observed. After single-dose s.c. injection, fesomersen was rapidly absorbed into the systemic circulation, with maximum fesomersen-equivalent (fesomersen-eq) concentrations (Cmax) in plasma observed within a few hours. After reaching Cmax, plasma fesomersen-eq concentrations declined in a biphasic fashion. The PD analyses showed that the injection of fesomersen led to dose-dependent reductions in FXI activity and increases in activated partial thromboplastin time (aPTT). The maximum observed PD effects were reached between Day 15 and 30, and FXI activity and aPTT returned to near-baseline levels by Day 90 after a single dose. The PK/PD profiles after a single injection were similar among the various ethnic groups. Collectively, the study results suggest that fesomersen has a favorable safety profile and predictable and similar PK and PD profiles across Chinese, Japanese, and Caucasian participants.

Assessment of the CYP3A4 Induction Potential by Carbamazepine: Insights from Two Clinical DDI Studies and PBPK Modeling.

In the past, rifampicin was well-established as strong index CYP3A inducer in clinical drug-drug interaction (DDI) studies. However, due to identified potentially genotoxic nitrosamine impurities, it should not any longer be used in healthy volunteer studies. Available clinical data suggest carbamazepine as an alternative to rifampicin as strong index CYP3A4 inducer in clinical DDI studies. Further, physiologically-based pharmacokinetic (PBPK) modeling is a tool with increasing importance to support the DDI risk assessment of drugs during drug development. CYP3A4 induction properties and the safety profile of carbamazepine were investigated in two open-label, fixed sequence, crossover clinical pharmacology studies in healthy volunteers using midazolam as a sensitive index CYP3A4 substrate. Carbamazepine was up-titrated from 100 mg twice daily (b.i.d.) to 200 mg b.i.d., and to a final dose of 300 mg b.i.d. for 10 consecutive days. Mean area under plasma concentration-time curve from zero to infinity (AUC(0-∞)) of midazolam consistently decreased by 71.8% (ratio: 0.282, 90% confidence interval (CI): 0.235-0.340) and 67.7% (ratio: 0.323, 90% CI: 0.256-0.407) in study 1 and study 2, respectively. The effect was adequately described by an internally developed PBPK model for carbamazepine which has been made freely available to the scientific community. Further, carbamazepine was safe and well-tolerated in the investigated dosing regimen in healthy participants. The results demonstrated that the presented design is appropriate for the use of carbamazepine as alternative inducer to rifampicin in DDI studies acknowledging its CYP3A4 inductive potency and safety profile.

Functional Textile Materials for Blocking COVID-19 Transmission.

The outbreak of COVID-19 provided a warning sign for society worldwide: that is, we urgently need to explore effective strategies for combating unpredictable viral pandemics. Protective textiles such as surgery masks have played an important role in the mitigation of the COVID-19 pandemic, while revealing serious challenges in terms of supply, cross-infection risk, and environmental pollution. In this context, textiles with an antivirus functionality have attracted increasing attention, and many innovative proposals with exciting commercial possibilities have been reported over the past three years. In this review, we illustrate the progress of textile filtration for pandemics and summarize the recent development of antiviral textiles for personal protective purposes by cataloging them into three classes: metal-based, carbon-based, and polymer-based materials. We focused on the preparation routes of emerging antiviral textiles, providing a forward-looking perspective on their opportunities and challenges, to evaluate their efficacy, scale up their manufacturing processes, and expand their high-volume applications. Based on this review, we conclude that ideal antiviral textiles are characterized by a high filtration efficiency, reliable antiviral effect, long storage life, and recyclability. The expected manufacturing processes should be economically feasible, scalable, and quickly responsive.

Mental health conditions of Chinese international students and associated predictors amidst the pandemic.

The current study aims to examine the mental health conditions and the associated predictors among Chinese international students. A sample of 256 Chinese international students aged 16 or above living primarily in Canada were asked to complete an online survey. Mental health conditions were assessed with the Depression, Anxiety, and Stress Scale-21 and the Physical and Mental Health Summary Scales. 15.3%, 20.4%, and 10.5% of respondents reported severe to extremely severe depression, anxiety, and stress levels, respectively. Univariate analysis of variance models and multiple linear regression models identified education and financial status as significant sociodemographic predictors while controlling for the effect of physical health status. Higher financial status and lower level of education were associated with better mental health conditions. These findings shed light on our understanding of mental health conditions and the risk factors among Chinese international students during the COVID-19 pandemic.

Progressive Design of a Ranatuerin-2 Peptide from Amolops wuyiensis: Enhancement of Bioactivity and In Vivo Efficacy.

Antimicrobial peptides (AMPs) that exert multiple functions are considered promising candidates to combat the bacterial drug resistance crisis. Nowadays, targeted peptide modification has been widely recognised to improve biological activity and make up for deficiencies in clinical applications such as toxicity. In this study, a helix-loop peptide was isolated and identified from the skin secretion of the Wuyi torrent frog Amolops wuyiensis, namely, ranatuerin-2-AW (R2AW) (GFMDTAKNVAKNVAATLLDKLKCKITGGC). Target modifications were made to R2AW to study the structure-activity relationships and to optimise its bioactivities. Five analogues were progressively designed via residue substitution and truncation and the antibacterial and anticancer activities were evaluated. We found that the serine-substitution and cyclic-domain-deletion products showed similar antibacterial activity to the natural peptide R2AW, implying that the disulphide bridge and Rana box were dispensable for the antibacterial activity of ranatuerin-2 peptides. Notably, the cationicity- and hydrophobicity-enhanced variant, [Lys4,19, Leu20]R2AW(1-22)-NH2, exhibited significantly optimised antibacterial and anticancer activities. Additionally, it killed bacteria by membrane disruption at a highly efficient rate. Moreover, [Lys4,19, Leu20]R2AW(1-22)-NH2 exerted potential in vivo efficacy in a methicillin-resistant Staphylococcus aureus (MRSA)-infected waxworm model. Overall, this study demonstrated some rational design ideas for optimising the dual antibacterial and anticancer activities of ranatuerin-2 peptides and it proposes [Lys4,19, Leu20]R2AW(1-22)-NH2 as an appealing candidate for therapeutic development.

IL-17A produced by invariant natural killer T cells and CD3+ CD56+ αGalcer-CD1d tetramer- T cells promote liver fibrosis in patients with primary biliary cholangitis.

Primary biliary cholangitis (PBC) is characterized as interlobular bile duct injury and fibrosis, which results from the loss of tolerance to self-antigens. However, the exact pathologic mechanism leading to injury and fibrosis in PBC patients is not fully understood. Therefore, in this study, we examined the role of the T cell subsets in PBC patients and healthy controls (HCs). A higher number of invariant Natual killer T (iNKT) cells as well as CD3+ CD56+ αGalcer-CD1d tetramer- T cells were found in patients with PBC compared with HCs. Moreover, these 2 T subpopulations produced significantly higher levels of Interleukin (IL)-17A in PBC patients than those in in HCs, which has also been positively correlated with the disease severity. Furthermore, the level of IL-17A produced by these 2 subpopulations was increased after stimulation of the autoantibodies in patients with PBC. Also, the elevated IL-17A levels promoted the PBC-related fibrosis, thus presenting a change in frequencies and functions of these cell phenotypes in the deterioration of the duct damage-related fibrosis. This study clarified PBC patients' distinct T subpopulations characteristics, providing evidence-based diagnostic and therapies for these patients. The correlation between unclassical T subsets and IL-17A may provide a novel target for the immunotherapy of PBC.

Clinical characteristics and prognosis of patient with leptospirosis: A multicenter retrospective analysis in south of China.

Purpose: Leptospirosis is a zoonotic disease caused by pathogenic spirochetes of the genus Leptospira. However, there is currently no consensual definition or diagnostic criteria for severe and different forms of leptospirosis. Therefore, more insight on clinical manifestations, risk factors, and outcomes of leptospirosis is warranted. The identification of leptospirosis with distinct clinical manifestations and prognosis in our population. Methods: Multiple correspondence analysis and hierarchical classification on principal components were presented to identify different clinical types of leptospirosis. The outcomes were clinical phenotypes, laboratory and imaging findings, and prognosis. Results: The 95 enrolled patients had median values of 54.0 years (39.0-65.0) for age, 9.0 (7.0-14.0) for total hospital stay lengths, of whom 86.3% was male and 40.0% was transferred to ICU. Three clinical types were distinguished: mild leptospirosis (n=43, 45.3%) with less organ dysfunction and shorter hospital stays; respiratory leptospirosis (n=28, 29.5%) with hemoptysis, and respiratory and circulatory failure; and hepato-renal leptospirosis (n=24, 25.3%) with worst liver and kidney dysfunction. Total hospital mortality was 15.8% and was associated with dyspnea and high levels of neutrophil counts. Conclusions: The identification of leptospirosis with distinct clinical manifestations and prognosis in our population may assist clinicians to distinguish leptospirosis-like disease. Moreover, dyspnea and neutrophil count were found to be independent risk factors for severe leptospirosis progression.

Forest ecosystem services and eco-compensation mechanisms in China.

Forests are a major terrestrial ecosystem providing multiple ecosystem services. However, the importance of forests is frequently underestimated from an economic perspective because of the externalities and public good properties of these services. Forest eco-compensation is a transfer mechanism that serves to internalize the externalities of forest ecosystem services by compensating individuals or companies for the losses or costs resulting from the provision of these services. China's current forest eco-compensation system is centered mainly on noncommercial forest. The primary measures associated with ecosystem services are (1) a charge on destructive activities, such as indiscriminate logging, and (2) compensation for individual or local activities and investments in forest conservation. The Compensation Fund System for Forest Ecological Benefits was first listed in the Forest Law of the People's Republic of China in 1998. In 2004, the Central Government Financial Compensation Fund, an important source for the Compensation Fund for Forest Ecological Benefits, was formally established. To improve the forest eco-compensation system, it is crucial to design and establish compensation criteria for noncommercial forests. These criteria should take both theoretical and practical concerns into account, and they should be based on the quantitative valuation of ecosystem services. Although some initial headway has been made on this task, the implementation of an effective forest eco-compensation system in China still has deficiencies and still faces problems. Implementing classification-based and dynamic management for key noncommercial forests and establishing an eco-compensation mechanism with multiple funding sources in the market economy are the key measures needed to conquer these problems and improve the forest eco-compensation system and China's forestry development in sequence.

lncRNA-HEIM Facilitated Liver Fibrosis by Up-Regulating TGF-ß Expression in Long-Term Outcome of Chronic Hepatitis B.

Background: Chronic liver fibrosis is an inevitable stage for the development of patients with chronic hepatitis B (CHB). However, anti-fibrotic therapies have been unsuccessful so far. The biological functions and molecular mechanisms of long non-coding RNAs (lncRNAs) in the host immune system during chronic hepatitis B virus (HBV) infection, especially in fibrosis, are still largely unknown. Method: The total RNA of peripheral blood mononuclear cells (PBMCs) from asymptomatic carriers (ASCs) or CHB receiving at least 8 years of anti-viral treatments was analyzed using Arraystar microarray and validated via quantitative real-time PCR (qRT-PCR). Correlation analysis was conducted based on correlation coefficients, Clusterprofile, and RNA Interactome Database (RAID). The functions of lncRNA in monocytes were determined via loss-of-function RNAi or gain-of-function lentivirus assays. The expression levels of mRNAs or proteins were evaluated using qRT-PCR, western blotting assay, or enzyme linked immunosorbent assays (ELISA). Results: A total of 1,042 mRNA transcripts (630 up-regulated and 412 down-regulated) were identified being differentially expressed between ASC and CHB patients. Through enrichment analysis we focused on the transforming growth factor beta (TGF-ß) signaling pathway and validated their expression in a larger cohort. Moreover, we found that lncRNA ENST00000519726 (lncRNA-HEIM) was highly expressed in monocytes and further up-regulated upon HBV infection. LncRNA-HEIM played an important role in CHB patients with long-term antiviral treatments, and its elevated expression was remarkably correlated with the TGF-ß signaling pathway, especially with the two members namely TGF-ß and SMAD4. Furthermore, altering the endogenous lncRNA-HEIM level in monocytes significantly affected the production of TGF-ß, as well as the fibrosis of hepatic stellate cells by affecting the expression of collagen I and α-smooth muscle actin (α-SMA). Conclusion: These findings not only added knowledge to the understanding of the roles of which lncRNA-HEIM played in the activation of HSCs in CHB patients with long-term medication, but also provided a promising therapeutic target in the future treatment for liver fibrosis.

Interleukin-33 as an early predictor of cetuximab treatment efficacy in patients with colorectal cancer.

BACKGROUND: Cetuximab is used for colorectal cancer (CRC) treatment. However, the early biomarker of treatment efficacy of cetuximab has not been identified. METHODS: After 1 year of cetuximab treatment, patients were divided into an effective group and an ineffective group. The interleukin-33 (IL-33) level and the distribution of lymphatic cells in patients were investigated by analyzing the peripheral blood mononuclear cells via flow cytometry analysis and ELISA. The correlation between IL-33 immunomodulatory effect and cetuximab treatment efficacy was determined through experiments in vivo and in vitro. RESULTS: The IL-33 level in the peripheral blood was increased at 4 weeks after cetuximab administration of effective group, meanwhile, the osteopontin (OPN) was reduced. Whereas neither IL-33 level nor OPN level of ineffective patients changed. In the effective group, the number of natural killer (NK) and CD8+ T cells were increased. Moreover, CD137 and CD107a expression on NK cells were higher in the effective group compared to the ineffective group. In vitro cetuximab treatment also increased the number of NK and CD8+ T cells as well as CD137 and CD107a expression upon IL-33 stimulation. Moreover, the secretion of OPN was inhibited by IL-33 administration in cetuximab-treated PBMCs from the effective group patients. IL-33 upregulated the cytotoxicity of NK cells and inhibited tumor cells growth in the effective cetuximab treatment mice. CONCLUSION: Effective cetuximab treatment induced a change of IL-33 and OPN at the early stage and triggered the NK cells antitumor activity. Consequently, significantly increased IL-33 level and decreased OPN level in the peripheral blood at the early treatment are proposed as potential predictors of cetuximab treatment efficacy.

Anomalous energy diffusion in two-dimensional nonlinear lattices.

Heat transport in one-dimensional (1D) momentum-conserved lattices is generally assumed to be anomalous, thus yielding a power-law divergence of thermal conductivity with system length. However, whether heat transport in a two-dimensional (2D) system is anomalous or not is still up for debate because of the difficulties involved in experimental measurements or due to the insufficiently large simulation cell size. Here we simulate energy and momentum diffusion in the 2D nonlinear lattices using the method of fluctuation correlation functions. Our simulations confirm that energy diffusion in the 2D momentum-conserved lattices is anomalous and can be well described by the Lévy-stable distribution. As is expected, we verify that 2D nonlinear lattices with on-site potentials exhibit normal energy diffusion, independent of the dimension. Contrary to the hypothesis of a 1D system, we further clarify that anomalous heat transport in the 2D momentum-conserved system cannot be corroborated by the momentum superdiffusion any longer. Our findings offer some valuable insights into mechanisms of thermal transport in 2D system.

Isolation, characterization and antimicrobial activities of polyacetylene glycosides from Coreopsis tinctoria Nutt.

Polyacetylene glycosides, (6Z, 12E)-tetradecadiene-8,10-diyne-1-ol-3(R)-O-ß-D-glucopyranoside (trivially named coreoside E) and (6Z, 12E)-tetradecadiene-8,10-diyne-1-ol-3(R)-O-ß-L-arabinopyranosyl-(1 â†’ 2)-ß-D-glucopyranoside (trivially named coreoside F), were isolated from buds of Coreopsis tinctoria Nutt., together with one known compound, coreoside B. Their chemical structures were elucidated by extensive spectroscopic analysis and on the basis of their chemical reactivities. Coreoside E exhibited high levels of antimicrobial activity against Staphylococcus aureus and Bacillus anthracis with minimum inhibitory concentrations of 27 ± 0.27 and 18 ± 0.40 µM, respectively, whereas coreoside F and coreoside B showed weak antimicrobial activity against S. aureus and B. anthracis.

[Therapeutic effect of three dimensional conformal radiotherapy in patients aged 65 years and older with non-small cell lung cancer].

BACKGROUND: Three dimensional conformal radiotherapy is one of the important treatment methods for patients aged 65 and older with inoperable non-small cell lung cancer (NSCLC). The aim of this study is to evaluate the efficacy of three dimensional conformal radiotherapy in elderly patients with inoperable NSCLC. METHODS: Thirty-one patients aged 65 and older with stage II and III NSCLC were treated by three dimensional conformal radiotherapy. Clinical effects, survival rates and pulmonary toxicity were analyzed. RESULTS: The overall response rate (CR+PR) was 87.1% (27/31). The 1, 2 and 3-year survival rates were 83.9% (26/31), 51.6% (16/31), and 25.8% (8/31) respectively. The relation of treatment efficacy and tumor size was observed. Acute radiation pneumonitis occurred in 3.2% (1/31) of the patients. Radiation pulmonary fibrosis occurred in 19.4% (6/31) of the patients. CONCLUSIONS: Three dimensional conformal radiotherapy is a safe and effective treatment for elderly patients with inoperable NSCLC and has a high survival rate.

Complete mitochondrial genome of Clouded angelshark (Squatina nebulosa).

The complete mitochondrial genome of the Squatina nebulosa was determined first in the present study. The mitochondrial genome is 16,698 nucleotides, encoding a standard set of 13 protein-coding genes and 2 ribosomal RNA genes, 22 tRNA genes, 1 control region and 1 origin of the light strand replication. The overall base composition of Squatina nebulosa is T 31.4%, C 24.1%, A 30.7%, and G 13.8%, and the A + T content is higher than G + C content. These mitogenome sequence data will play an important role in population genetics and phylogenetic analysis of the Suqatinids.