Characterization and genomic analysis of a lytic Stenotrophomonas maltophilia short-tailed phage A1432 revealed a new genus of the family Mesyanzhinovviridae.

Stenotrophomonas maltophilia (S. maltophilia) is an emerging opportunistic pathogen that exhibits resistant to a majority of commonly used antibiotics. Phages have the potential to serve as an alternative treatment for S. maltophilia infections. In this study, a lytic phage, A1432, infecting S. maltophilia YCR3A-1, was isolated and characterized from a karst cave. Transmission electron microscopy revealed that phage A1432 possesses an icosahedral head and a shorter tail. Phage A1432 demonstrated a narrow host range, with an optimal multiplicity of infection of 0.1. The one-step growth curve indicated a latent time of 10 min, a lysis period of 90 min, a burst size of 43.2 plaque-forming units per cell. In vitro bacteriolytic activity test showed that phage A1432 was capable to inhibit the growth of S. maltophilia YCR3A-1 in an MOI-dependent manner after 2 h of co-culture. BLASTn analysis showed that phage A1432 genome shares the highest similarity (81.46%) with Xanthomonas phage Xoo-sp2 in the NCBI database, while the query coverage was only 37%. The phage contains double-stranded DNA with a genome length of 61,660 bp and a GC content of 61.92%. It is predicted to have 79 open reading frames and one tRNA, with no virulence or antibiotic resistance genes. Phylogenetic analysis using terminase large subunit and DNA polymerase indicated that phage A1432 clustered with members of the Bradleyvirinae subfamily but diverged into a distinct branch. Further phylogenetic comparison analysis using Average Nucleotide Identity, proteomic phylogenetic analysis, genomic network analysis confirmed that phage A1432 belongs to a novel genus within the Bradleyvirinae subfamily, Mesyanzhinovviridae family. Additionally, phylogenetic analysis of the so far isolated S. maltophilia phages revealed significant genetic diversity among these phages. The results of this research will contribute valuable information for further studies on their morphological and genetic diversity, will aid in elucidating the evolutionary mechanisms that give rise to them.

Biomarkers of lipid metabolism in gastric cancer: a case control study.

BACKGROUND: The aim of this study was to explore the correlation between biomarkers of lipid metabolism and gastric cancer. METHODS: 1120 gastric cancer patients and 1134 health examiners enrolled in this study. The clinic data and serum lipid level, including Total cholesterol (TC), Triglyceride (TG), Low-density lipoprotein cholesterol (LDL-C) and High-density lipoprotein cholesterol (HDL-C), were collected. RESULTS: Serum TG and LDL-C levels in patients with gastric cancer were higher than those in the control group. HDL-C levels were lower than the control group (P < 0.05). HDL-C and LDL-C were significantly correlated with the risk of gastric cancer. Concentrating on clinicopathological features, increased TG was more frequently in male patients with distal gastric cancer, N0 stage and early TNM stage. Increased TC was more frequently in early T, N and TNM stage. Decreased HDL-C was more common in distal location and low-undifferentiated gastric cancer. LDL-C elevation was more common in distal gastric cancer and early T stage. CONCLUSIONS: The serum lipid level of gastric cancer patients was higher than healthy controls. HDL-C and LDL-C abnormal correlated with gastric cancer risk. However, as the progresses of gastric cancer, poor patient intake, increased tumor consumption, and continuous declining in nutritional status, the levels of TC and TG gradually decreased in advanced gastric cancer.

Characteristics and whole-genome analysis of a novel Pseudomonas syringae pv. tomato bacteriophage D6 isolated from a karst cave.

Pseudomonas syringae is a gram-negative plant pathogen that infects plants such as tomato and poses a threat to global crop production. In this study, a novel lytic phage infecting P. syringae pv. tomato DC3000, named phage D6, was isolated and characterized from sediments in a karst cave. The latent period of phage D6 was found to be 60 min, with a burst size of 16 plaque-forming units per cell. Phage D6 was stable at temperatures between 4 and 40 °C but lost infectivity when heated to 70 °C. Its infectivity was unaffected at pH 6-10 but became inactivated at pH ≤ 5 or ≥ 12. The genome of phage D6 is a linear double-stranded DNA of 307,402 bp with a G + C content of 48.43%. There is a codon preference between phage D6 and its host, and the translation of phage D6 gene may not be entirely dependent on the tRNA library provided by the host. A total of 410 open reading frames (ORFs) and 14 tRNAs were predicted in its genome, with 92 ORFs encoding proteins with predicted functions. Phage D6 showed low genomic similarity to known phage genomes in the GenBank and Viral sequence databases. Genomic and phylogenetic analyses revealed that phage D6 is a novel phage. The tomato plants were first injected with phage D6, and subsequently with Pst DC3000, using the foliar spraying and root drenching inoculum approach. Results obtained after 14 days indicated that phage D6 inoculation decreased P. syringae-induced symptoms in tomato leaves and inhibited the pathogen's growth in the leaves. The amount of Pst DC3000 was reduced by 150- and 263-fold, respectively. In conclusion, the lytic phage D6 identified in this study belongs to a novel phage within the Caudoviricetes class and has potential for use in biological control of plant diseases.

First Report of Powdery Mildew on Viburnum chinshanense Caused by Erysiphe pseudoviburni in China.

Viburnum chinshanense, a deciduous shrub in the family Caprifoliaceae, is a dominant tree distributed mainly in the North-Central and South-Central regions of China (Zhu et al. 2023). Because of its lush white flowers and vibrant red fruits, V. chinshanense is used widely as ornamental tree in China. In May 2022, severe powdery mildew symptoms were observed on V. chinshanense on the Huaxi Campus of Guizhou Normal University, Guiyang, China. The incidence was approximately 75% among 80 V. chinshanense plants observed. White mycelia were present on both adaxial and abaxial leaf sides, but not on fruits, petioles, or stems. Infected leaves showed slight chlorosis and twisting. The mycelia were amphigenous, forming small-to-large patches, often sparse on the upper leaf surface, but mostly confluent on the lower leaf surface. Hyphae were hyaline, 4-7 µm wide. Hyphal appressoria were lobed to multilobed, in opposite pairs or solitary. Conidiophores were erect, straight, or somewhat flexuous, 60-130 µm long (n = 30). Foot cells were subcylindrical to slightly curved-sinuous at the base, 20-40 × 6-10 µm (n = 30) in size, followed by 1-3 shorter cells. Conidia formed singly, occasionally two to three in a chain. Conidia were ellipsoid to ovoid, cylindrical, and 24-40 × 16-20 µm (n = 50). No fibrosin bodies were observed on the conidia. Chasmothecia were subglobose, 56-115 µm in diameter. The appendages were 35-70 µm long. Based on these morphological characteristics, the powdery mildew fungus was identified as Erysiphe pseudoviburni (Bradshaw et al. 2020). To confirm the identification, the ribosomal DNA internal transcribed spacer (ITS) and the ribosomal large subunit (LSU) region were amplified and sequenced using the ITS1/ITS4 primer pair (White et al. 1990) and the NL1/NL4 primer pair (Ziemiecki et al. 1990), respectively. The obtained 643-bp ITS sequence (GenBank accession no. ON729292) had 99.84% identity with E. pseudoviburni strains KUS-F27310 (MN431595) and MUMH0001 (LC009904). The obtained 593-bp LSU sequence (ON729293) had 99.83% identity with E. pseudoviburni (LC009904 and MN431595). Based on the phylogenetic analysis of the combined ITS and LSU dataset (Bradshaw et al. 2020), the isolate (GZVD-1) was grouped in a clade with the E. pseudoviburni strains KUS-F27319, KUS-F27310, and MUMH0001. To fulfill Koch's postulates, leaves of three healthy potted V. chinshanense plants were inoculated by gently pressing with diseased leaves. Non-contact plants were used as controls. All plants were incubated in a greenhouse at 25 ± 2°C, 80% relative humidity. Similar powdery mildew symptoms were observed on the inoculated plants 12 days after inoculation, whereas the control plants remained symptomless. The reisolated fungus from the inoculated plants was morphologically identical to that on originally diseased plants. ITS and LSU sequences of the reisolated fungus showed 100% identity with ON729292 and ON729293, respectively. E. pseudoviburni has previously been reported to infect some Viburnum species, including V. sieboldii in Japan (Takamatsu et al. 2015) and V. odoratissimum in South Korea (Bradshaw et al. 2020). To the best of our knowledge, this is the first report of powdery mildew caused by E. pseudoviburni on V. chinshanense in China. This work expands the known host range of E. pseudoviburni in the Viburnum genus.

LncRNA DGUOK-AS1 Promotes Cell Progression in Lung Squamous Cell Carcinoma by Regulation of miR-653-5p/SLC6A15 Axis.

Long noncoding RNA (lncRNA) plays a key role in regulating cancer development. LncRNA deoxyguanosine kinase antisense RNA 1 (DGUOK-AS1) has been reported as a promoter in tumor. The work was designed to further investigate the mechanism of action of DGUOK-AS1 in lung squamous cell carcinoma (LUSC). DGUOK-AS1 level in LUSC cells was measured using RT-qPCR. Counting Kit-8 assays and colony forming assays were performed to evaluate LUSC cell viability and proliferation. Transwell assays were performed to detect cell migration and invasion. Luciferase reporter and RNA pulldown assays were used to verify the binding capacity of DGUOK-AS1 and miR-653-5p. RNA immunoprecipitation assays were performed to verify the relationship of DGUOK-AS1, miR-653-5p, and SLC6A15. DGUOK-AS1 was highly expressed in LUSC cells. DGUOK-AS1 knockdown suppressed LUSC cell proliferation, migration, and invasion. SLC6A15 was demonstrated to be targeted by miR-653-5p, and DGUOK-AS1 interacted with miR-653-5p to modulate SLC6A15 level in LUSC cells. Overexpression of SLC6A15 reversed the suppressive effects of DGUOK-AS1 knockdown on LUSC cell processes. In conclusion, DGUOK-AS1 promotes malignant behaviors of LUSC cells by upregulating SLC6A15 level through interaction with miR-653-5p.

Comparison between thoracic low-dose computed tomography and conventional-dose computed tomography in evaluating anemia: A preliminary study in a Chinese screening cohort.

Purpose: To investigate and evaluate the value of thoracic low dose computed tomography (LDCT) scan in the diagnosis of anemia. Materials and methods: 661 patients who received thoracic computed tomography (CT) examination and underwent a peripheral blood examination were retrospectively included. 341 patients underwent conventional dose CT (CDCT), and 320 patients underwent LDCT. Regions of interest (ROI) were placed on the left ventricular cavity (LV), descending aorta (DAo), and interventricular septum (IVS). The corresponding CT attenuation was measured, and the CT attenuation difference between LV and IVS (IVS-LV) and between DAo and IVS (IVS-DAo) was calculated, respectively. One-way analysis of variance (ANOVA) and linear regression were performed to analyze the relationship between these indicators and Hb levels. The receiver operating characteristic (ROC) curve was used to evaluate prediction performance. Results: Both attenuation on LDCT and CDCT showed significant differences between the healthy group and the anemic group (P < 0.05). In the LDCT group, the LV and DAo were more relevant with the hemoglobin (Hb) level (correlation coefficient 0.618 and 0.602) than other indicators, with AUCs of 0.815 (95% CI: 0.763-0.868) and 0.803 (95% CI: 0.747-0.859), respectively. The linear regression formulas for Hb level with the LV and DAo were 19.14 + 0.15 × HU [95% CI: (16.52, 21.75) + (0.12, 0.17) × HU] and 19.46 + 0.16 × HU [95% CI: (16.55, 22.36) + (0.13, 0.18) × HU], respectively. Youden's index indicated that 37.5 HU and 38.5 HU were the best thresholds to diagnose anemia for LV and DAo, respectively. In the CDCT group, the LV and IVS-LV got obviously higher correlation coefficients (0.813 and 0.812), with AUCs of 0.831 (95% CI: 0.786-0.877) and 0.851 (95% CI: 0.808-0.894), respectively. The optimal thresholds for LV and IVS-LV were 40.5 HU and 9.5 HU, respectively. Conclusion: In LDCT examinations, an approximation of Hb level and detecting of anemia can be conducted based on simple attenuation measurements.

Arthrobacter cavernae sp. nov., a novel actinobacterium isolated from sediment of karst cave.

A novel, Gram-stain-positive, aerobic, non-endospore-forming, non-motile and rod-shaped bacterium designated PO-11T was isolated from sediment of karst cave collected in Libo county, Guizhou Province, PR China. The isolate grew optimally on R2A agar at 25 °C, pH 8.0 and with 0.5 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that PO-11T belonged to the genus Arthrobacter and was most closely related to Arthrobacter methylotrophus TGAT (98.3 % sequence similarity), Arthrobacter alkaliphilus LC6T (97.7 %) and Arthrobacter ramosus CCM1646T (97.1 %). Genome sequencing revealed a genome size of 4 073 119 bp and the genomic DNA G+C content was 66.16 mol%. Its DNA-DNA relatedness values with A. methylotrophus TGAT, A. alkaliphilus LC6T and A. ramosus CCM1646T were 23.0, 22.9 and 23.2 %, respectively. The main fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The major respiratory quinone was MK-9(H2). The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, glycolipid, phosphatidylethanolamine, phosphatidylinositol and unidentified lipids. Thus, based on phylogenetic and phenotypic and chemotaxonomic data, strain PO-11T represents a novel species of the genus Arthrobacter, for which the name Arthrobacter cavernae sp. nov. is proposed. The type strain is strain PO-11T (=CCTCC AB 2021070T=LMG 32459T).

THE INFLUENCE OF LOW-DOSE OCCUPATIONAL RADIATION EXPOSURE ON PERIPHERAL BLOOD CELLS IN A COHORT OF CHINESE MEDICAL RADIATION WORKERS.

OBJECTIVES: The study aims to assess the change of peripheral blood cell numbers following protracted low-dose radiation exposure among medical radiation workers. METHODS: A cohort of 375 Chinese medical workers were followed for 5 years (2015-19) and recorded the changes in blood cells and cumulative doses. T-test, least significant difference-T test, variance analysis and correlation analysis were utilized in this study. RESULTS: Compared with the control group, the white blood cells, hemoglobin counts and the ratio of eosinophils in the study group showed a downward trend. The differences in blood cells between groups were mainly found in the number of red blood cells. In a short cumulative time, such as 1 or 3 years, a correlation between the cumulative dose and the quantity of blood cells was detected, but not at 5 years. CONCLUSIONS: There is no significant difference in the blood cell counts between different types of work, and the long-term cumulative dose has not been statistically correlated with the number of blood cells. So that the number of peripheral blood cells can no longer be used as a good indicator of radiation damage.

Actively tunable multi-band terahertz perfect absorber due to the hybrid strong coupling in the multilayer structure.

In this work, we propose a multi-band terahertz perfect absorber employing the topological photonic crystal combined with VO2 and graphene. The hybrid strong coupling among the topological photonic state, the Tamm plasmon polaritons excited around the interfaces of VO2 and graphene results in the three perfect absorption bands. Benefiting from the reversible insulator-metal phase transition of VO2 and the tunable Fermi level of graphene, it can actively switch among no absorption, single-band, dual-band and multi-band absorptions around 1THz, with the absorption frequencies tunable as well. Besides, the absorption bands are sensitive to the incident angle in almost the same dispersion rate, with high absorptions in a large angle range. Moreover, the splitting frequencies between the adjacent absorption peaks strongly depend on the pair number of the alternating multilayers. Apart from the three absorption bands, there are still many absorption peaks in the large frequency range resulting from the standing waves, including other 7 peaks above 0.9 between 0.83THz and 1.55THz. Such a tunable multi-band absorber with multiple modulation methods may find extended applications in active integrated terahertz devices.

The mutation landscape of multiple cancer predisposition genes in Chinese familial/hereditary breast cancer families.

OBJECTIVE: Approximately 5%-10% of breast cancer (BC) patients display familial traits that are genetically inherited among the members of a family. The purpose of this study was to profile the germline mutations in 43 genes with different penetration rates and their correlations with phenotypic traits in Chinese familial BC families. METHODS: Ion Torrent S5™-based next generation sequencing was conducted on 116 subjects from 27 Chinese familial BC families. RESULTS: Eighty-one germline mutations in 27 BC predisposition genes were identified in 82.8% (96/116) of the cases. Among these, 80.8% of the mutated genes were related to DNA damage repair. Fourteen possible disease-causing variants were identified in 13 of 27 BC families. Only 25.9% (7/27) of the BC families exhibited hereditary deficiency in BRCA1/2 genes, while 22.2% of the BC families exhibited defects in non-BRCA genes. In all, 41.7% (40/96) of the mutation carriers had BRCA mutations, 88.5% (85/96) had non-BRCA mutations, and 30.2% (29/96) had both BRCA and non-BRCA mutations. The BC patients with BRCA mutations had a higher risk of axillary lymph node metastases than those without mutations (P < 0.05). However, the BC patients with non-BRCA mutations frequently had a higher occurrence of benign breast diseases than those without mutations (P < 0.05). CONCLUSIONS: In addition to BRCA1/2, genetic variants in non-BRCA DNA repair genes might play significant roles in the development of familial/hereditary BC. Therefore, profiling of multiple BC predisposition genes should be more valuable for screening potential pathogenic germline mutations in Chinese familial/hereditary BC.

Actively tunable bi-functional metamirror in a terahertz band.

In this work, we have proposed an actively tunable bi-functional metamirror based on a bi-layer graphene structure. The metamirror acts as a spin-selective absorber under circularly polarized incidence, which behaves as nearly perfect absorption and reflection for right and left circularly polarized waves, respectively, leading to giant circular dichroism. On the other hand, it is a polarization converter under linearly polarized incidence, which reflects the linearly polarized wave into a left circularly polarized wave. Both the spin-selective absorber and the polarization converter can be actively switched between ON and OFF states, with the working frequency controlled by the voltages applied to graphene. Moreover, the metamirror is insensitive to the incidence angle, which contributes to its application as a stable single-mode spin-selective absorber and polarization converter. This bi-layer graphene structure offers a method to construct actively tunable bi-functional metamirrors, which may achieve potential applications in integrated devices, such as active spin detectors, absorbers, and quarter-wave plates for terahertz waves.

Tuning of the polariton modes induced by longitudinal strong coupling in the graphene hybridized DBR cavity.

In this Letter, we construct a graphene hybridized distributed Bragg reflector (DBR) cavity, where spatially longitudinal strong coupling occurs between the Tamm plasmon polaritons (TPPs) existing around the graphene layer and the cavity mode (CM) existing in the DBR cavity. As a result, two hybrid polariton modes emerge, which contain both the TPP and the CM components. In the simulation, we demonstrate that the resonant frequencies and the damping rates of the polariton modes can be actively tuned by the graphene Fermi level and the incident angle of light. Besides, the coupling strength and the damping rates are also passively tuned by the pair number of the layers in the DBR. Theoretically, we analyze the TPP-CM strong coupling by the coupled harmonic oscillator equations, which help to explain the regulation process. The controllable TPP-CM longitudinal strong coupling with two absorption bands may achieve potential applications in developing graphene-based active optoelectronic and polaritonic devices in terahertz waves.

The Association Between Metabolic Syndrome and Gastric Cancer in Chinese.

Background: Metabolic syndrome (MetS) play a carcinogenic role in variety of cancers and influence the prognosis of cancer patients both systemically and hormonally. Methods: The data of clinicopathologic features and MetS of 808 gastric cancer patients and 1,146 randomly healthy controls were analyzed retrospectively. Results: Higher TG level, lower HDL-C level and higher hypertension frequency were observed in all gastric cancer patients when compared with healthy controls. While, gastric cancer patients had greater waist circumference only in females. Among three definitions of MetS, the MetS identified by the Chinese Diabetes Society (CDS) was associated with the most significant increasing risk of gastric cancer. Comparing all gastric cancer patients with healthy controls, OR of gastric cancer was enhanced by various individual components of the MetS, including higher TG level, lower HDL-C level, hypertension and diabetes; In male subgroup, OR of gastric cancer was enhanced by higher BMI, hypertension and diabetes; In females, OR of gastric cancer was enhanced by lower HDL-C, hypertension and diabetes. MetS was associated with poor differentiated carcinoma, more advanced pathological T, N stage and TNM stage of gastric cancer. Conclusion: The presence of MetS and its components were increased in gastric cancer, especially in gastric cancer patients with poor differentiation and advanced stage, which implies that metabolic disorder may play an important role in the development of gastric cancer.

Tumor-infiltrating Treg, MDSC, and IDO expression associated with outcomes of neoadjuvant chemotherapy of breast cancer.

BACKGROUND: Regulatory T cells(Tregs) and myeloid-derived suppressor cells(MDSCs) represent two immunosuppressive cell populations that are important in the establishment and maintenance of cancer immune tolerance. MDSCs can express IDO and promote immune tolerance via expansion of Treg cell. METHOD: We use needle biopsy breast cancer tissues prior to neoadjuvant chemotherapy(NCT) staining for CD33, Foxp3 and IDO by immunohistochemistry to evaluate whether they were correlated with subsequent treatment responses in breast cancer. RESULTS: Expressions of IDO, CD33+MDSCs and Foxp3+Tregs were correlated with each other. Immunohistochemical double staining revealed that IDO expression in CD33+MDSCs was positively correlated with Foxp3+Tregs (P < 0.05). CD33+MDSCs, Foxp3+Tregs, and IDO expression in tumor tissues were associated with advanced clinical stage prior to NCT (P < 0.05). CD33+MDSCs, Foxp3+Tregs, IDO expression, IDO expression in CD33+MDSCs and clinical T3-T4 stage prior to NCT, pathological T3-T4 stage, ER(+), luminal type were correlated with clinical responses of PD+SD (P < 0.05). Multivariate analysis showed that CD33+MDSCs, IDO expression, IDO expression in CD33+MDSCs, and advanced pathological T stage were risk factors for PD+SD. Focusing on the pCR of NCT, only CD33+MDSCs, clinical T3-T4, and N1-N3 stage prior to NCT were associated with no-pCR (P < 0.05). The multivariate analysis showed that advanced clinical T stage and N stage were risk factors for no-pCR. Clinical stage prior to NCT were significantly correlated with progression free survival (P = 0.021), while Foxp3+Tregs and clinical T stage were significantly correlated with overall survival (P = 0.022 and P = 0.001, respectively). Foxp3+Treg was significant risk factor for overall survival after adjusting covariates by COX regression. CONCLUSION: Tumor-infiltrating MDSCs, Tregs, IDO expression and IDO expression in MDSCs were correlated with clinicopathological features, NCT response, and prognosis of breast cancer patients, suggesting that they might be potential markers for clinical outcomes of NCT and help clinical decision-making for improved therapies for breast cancer.

New Approaches for Biaryl-Based Phosphine Ligand Synthesis via P═O Directed C-H Functionalizations.

Given the important influence of phosphine ligands in transition metal-catalyzed reactions, chemists have searched for straightforward and efficient methodologies for the synthesis of diverse phosphine ligands. Although significant progress has been made in this aspect over the past decades, the development of new phosphorus-containing ligands with properties superior to their predecessors remains a central task for chemists. Recently, researchers have demonstrated that biphenyl monophosphine ligands function as highly efficient ligands for transition-metal-catalyzed organic transformations, especially for reactions where chelating bisphosphine ligands cannot be used. In 1998, Buchwald introduced a new class of air-stable phosphine ligands based on the dialkylbiaryl phosphine backbone. These ligands have been successfully used for a wide variety of palladium-catalyzed carbon-carbon, carbon-nitrogen, and carbon-oxygen construction processes as well as serving as supporting ligands for a number of other reactions. At the same time, the use of the biphenyl monophosphine ligands often allows reactions to proceed with short reaction times and low catalyst loadings and under mild reaction conditions. However, the synthesis of chiral biphenyl monophosphine ligands, especially those the chirality of which is due to biaryl axial chirality, is very limited. In this Account, we summarize our methodologies for the synthesis of this kind of biphenyl monophosphine ligands including the P═O directed C-H functionalization, P═O directed diastereoselective C-H functionalization, P═O directed enantioselective C-H functionalization, and metal-free diastereoselective radical oxidative C-H amination under mild reaction conditions. With these methods, a series of biphenyl phosphine ligand precursors containing achiral or axially chiral centers and precursors possessing both axial chirality and a chirogenic phosphorus center with different electronic properties and steric effect have been obtained under different reaction conditions. For the preparation of chiral biphenyl monophosphine ligands, which not only possess axial chirality but in many cases also possess chirality at phosphorus, the primary means of introducing chirality is through the use of the menthyl phenylphosphinate. As a chiral auxiliary group, the menthyl phenylphosphinate has some unique features: (i) it is easy to prepare; (ii) the products contain both axial chirality and central chirality on the phosphorus atom; (iii) the menthyl group could easily be transformed into other functional groups, which is crucial for the diversity of the corresponding biphenyl ligands. In our reaction, the P═O group not only acts as the directing group but also facilitates the construction of the phosphine ligands. In addition, the application of these products in asymmetric catalysis has also been studied with good results obtained in some reactions. The further application of these ligands, especially the chiral biphenyl monophosphine ligands in catalysis reactions is underway in our laboratory, and we hope different kinds of reactions will be achieved with these ligands.

IDO1: An important immunotherapy target in cancer treatment.

Indoleamine 2,3-dioxigenase 1 (IDO1) acts in pathogenic inflammatory processes and engender immune tolerance to tumor antigens. IDO1 can decrease the tryptophan and produce a series of toxic kynurenine metabolites to promote the immune toleration via GCN2 pathway, mTOR pathway, toxic effect of kynurenine and favoring differentiation of Tregs. IDO1 can be induced in most human cells, especially APCs and cancer cells through canonical and non-canonical NF-κB and Jak/STAT pathways, as well as PKC and TGF-ß signaling pathways. A series of human cancers over-express IDO1 in a constitutive way. Thus, IDO1 is likely to be an attractive target for developing inhibitors of tumor treatments. Many preclinical and clinical trials have been underway and suggest that IDO1 inhibitor maybe an effective tool against a wide range of cancers. However, the IDO1 inhibitor alone had been verified that to be disappointment in achieving effective antitumor efficacy. Concentrating on its molecular mechanism in immune toleration and complex environments of cancer, IDO1 inhibitor could cooperate with chemotherapies and other immune target inhibitors to lessen the tumor.

P(O)R2-Directed Enantioselective C-H Olefination toward Chiral Atropoisomeric Phosphine-Olefin Compounds.

An effective synthesis of chiral atropoisomeric biaryl phosphine-olefin compounds via palladium-catalyzed enantioselective C-H olefination has been developed for the first time. The reactions are operationally simple, tolerate wide functional groups, and have a good ee value. Notably, P(O)R2 not only acts as the directing group to direct C-H activation in order to make a useful ligand but also serves to facilitate composition of the product in a useful manner in this transformation.

Indoleamine-2,3-dioxygenase and Interleukin-6 associated with tumor response to neoadjuvant chemotherapy in breast cancer.

PURPOSE: Indoleamine-2,3-dioxygenase (IDO) and Interleukin-6 (IL-6) contribute to poor therapeutic effects, tumor relapse and aggressive tumor growth. IDO and IL-6 incorporate a positive feedback signal loop to maintain IDO and IL-6 constitutive expression and facilitate tumor progression. RESULTS: IDO expression was associated with IL-6 expression and plasma IL-6 level (P<0.05). Concentrating on clinicopathological features prior neoadjuvant chemotherapy, both IDO expression and plasma IL-6 level were associated with clinical T stage and N stage (P<0.05). IL-6 expression was associated with clinical T stage (P=0.016). The co-expression of IDO/IL-6 was correlated with clinical T, N stage and estrogen receptor (ER) status (P<0.05). IDO, IL-6 expression, clinical T stage, pathological T stage, ER status and Luminal type were correlated with clinical response to neoadjuvant chemotherapy (P<0.05). Multivariate analysis showed that IDO expression were correlated with clinical response to neoadjuvant chemotherapy (P=0.034). IL-6 expression and pathological T stage were correlated with pCR (P<0.05). In the multivariate analysis, postoperative pathological T stage associated with pCR (P=0.041). In the prognostic analysis, only clinical T stage was significant correlated with overall survival (P=0.003). MATERIALS AND METHODS: 46 breast cancer patients received neoadjuvant chemotherapy enrolled in this study. Immunohistochemistry was applied for evaluating IDO and IL-6 expression in biopsy tissues prior neoadjuvant chemotherapy. Immunofluorescence was applied to observe the co-localization of IDO and IL-6. Serum IL-6 level was examined via ELISA. The associations between IDO, IL-6, Serum IL-6 level and clinicopathological features, response to neoadjuvant chemotherapy were analyzed. CONCLUSION: IDO and IL-6 expression associated with advanced breast cancer and poor response to neoadjuvant chemotherapy.

The effect of antisense inhibitor of miRNA 106b∼25 on the proliferation, invasion, migration, and apoptosis of gastric cancer cell.

Accumulating data has demonstrated that miRNA 106b∼25, which are composed of the highly conserved miRNA 106b, miRNA 93, and miRNA 25, play carcinogenic roles in cancers. We investigated the expression of miRNA 106b∼25 in gastric cancer cells (SGC 7901, MGC 803, BGC 823) and normal gastric epithelial cell then inhibited miRNA 106b∼25 expression via transiently transfecting their antisense inhibitor. After miRNA 106b∼25 cluster was inhibited, MTT, Scratch test, Transwell invasion test, and flow cytometry were applied to investigate the proliferation, invasion, migration, cell cycle, and apoptosis of gastric cancer cell. The expression of miRNA 106b, miRNA 93, and miRNA 25 in gastric cancer cells SGC 7901, MGC 803, and BGC 823 was significantly higher than in gastric epithelial cell GES-1. The most significant suppression of miRNA 106b∼25 expressions can be detected in MGC 803 cell after transiently transfecting their antisense inhibitors. So, MGC 803 cell was selected as our research object. After inhibiting miRNA 106b and miRNA 93 respectively and combined, the proliferation, migration, and invasion of gastric cancer cell MGC 803 were significantly suppressed. The most significant suppression was observed in combined inhibiting group. After miRNA 106b∼25 cluster was inhibited respectively or combined, more gastric cancer cells were arrested in the G0G1 phase. However, there was no statistical difference in comparing with control groups. While the percentages of apoptotic cells increased after miRNA 106b∼25 cluster was inhibited, the statistical difference was detected only in combined inhibiting group. Inhibiting miRNA 106b∼25 cluster via transfecting antisense inhibitor can influence biological behavior of gastric cancer cell.