Construction of an Artificial Light-Harvesting System with Efficient Photocatalytic Activity in an Aqueous Solution Based on a FRET-Featuring Metallacage.

Over the past few decades, the design and construction of high-efficiency artificial light-harvesting systems (LHSs) involving multistep fluorescence-resonance energy transfer (FRET) processes have gradually received considerable attention within wide fields ranging from supramolecular chemistry to chemical biology and even materials science. Herein, through coordination-driven self-assembly, a novel tetragonal prismatic metallacage featuring a FRET process using tetraphenylethene (TPE) units as donors and BODIPY units as acceptors has been conveniently synthesized. Subsequently, taking advantage of supramolecular hydrophobic interactions, a promising artificial LHS involving two-step FRET processes from TPE to BODIPY and then to Nile Red (NiR) has been successfully fabricated in an aqueous solution using the FRET-featuring metallacage, NiR, and an amphiphilic polymer (mPEG-DSPE). Notably, this obtained aqueous LHS exhibits highly efficient photocatalytic activity in the dehalogenation of a bromoacetophenone derivate. This study provides a unique strategy for fabricating artificial LHSs in aqueous solutions with multistep FRET processes and further promotes the future development of mimicking the photosynthesis process.

Predictive value of the neutrophil to lymphocyte ratio for disease deterioration and serious adverse outcomes in patients with COVID-19: a prospective cohort study.

BACKGROUND: Early identification of patients who are at high risk of poor clinical outcomes is of great importance in saving the lives of patients with novel coronavirus disease 2019 (COVID-19) in the context of limited medical resources. OBJECTIVE: To evaluate the value of the neutrophil to lymphocyte ratio (NLR), calculated at hospital admission and in isolation, for the prediction of the subsequent presence of disease progression and serious clinical outcomes (e.g., shock, death). METHODS: We designed a prospective cohort study of 352 hospitalized patients with COVID-19 between January 9 and February 26, 2020, in Yichang City, Hubei Province. Patients with an NLR equal to or higher than the cutoff value derived from the receiver operating characteristic curve method were classified as the exposed group. The primary outcome was disease deterioration, defined as an increase of the clinical disease severity classification during hospitalization (e.g., moderate to severe/critical; severe to critical). The secondary outcomes were shock and death during the treatment. RESULTS: During the follow-up period, 51 (14.5%) patients' conditions deteriorated, 15 patients (4.3%) had complicated septic shock, and 15 patients (4.3%) died. The NLR was higher in patients with deterioration than in those without deterioration (median: 5.33 vs. 2.14, P < 0.001), and higher in patients with serious clinical outcomes than in those without serious clinical outcomes (shock vs. no shock: 6.19 vs. 2.25, P < 0.001; death vs. survival: 7.19 vs. 2.25, P < 0.001). The NLR measured at hospital admission had high value in predicting subsequent disease deterioration, shock and death (all the areas under the curve > 0.80). The sensitivity of an NLR ≥ 2.6937 for predicting subsequent disease deterioration, shock and death was 82.0% (95% confidence interval, 69.0 to 91.0), 93.3% (68.0 to 100), and 92.9% (66.0 to 100), and the corresponding negative predictive values were 95.7% (93.0 to 99.2), 99.5% (98.6 to 100) and 99.5% (98.6 to 100), respectively. CONCLUSIONS: The NLR measured at admission and in isolation can be used to effectively predict the subsequent presence of disease deterioration and serious clinical outcomes in patients with COVID-19.

The first total synthesis of rebaudioside R.

With easily available monosaccharides and steviol as starting materials, the first total synthesis of rebaudioside R with a xylosyl core in the C13-OH linked sugar chain was accomplished via two distinct approaches. The first approach features the stepwise installation of branch-sugar residues via an order of C2-OH first and then C3-OH of the xylosyl core, laying a firm foundation for the synthesis of analogues with different branch sugars, while the second route features the introduction of the C13 trisaccharide sugar chain via a convergent strategy, securing the overall synthetic efficiency. Through the synthetic study, the effect of protecting groups (PGs) at the vicinal hydroxy group on the reactivity of OH acceptors was illustrated.

Precision syntheses of molecular necklaces based on coordination interactions.

Molecular necklaces (MNs) are mechanically interlocked molecules that have attracted considerable attention due to their delicate structures and potential applications, such as in the syntheses of polymeric materials and DNA cleavage. However, complex and lengthy synthetic routes have limited development of further applications. Owing to their dynamic reversibility, strong bond energy and high orientation, coordination interactions were employed to synthesize MNs. In this review, progress in the coordination-based MNs has been summarized, with emphasis on design strategies and potential applications based on coordination interactions.

The novel HLA-DQB1*03:03:29 allele, identified by sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-DQB1*03:03:29 differs from HLA-DQB1*03:03:02:01 by one nucleotide in exon 2.

MicroRNA-98 and microRNA-214 post-transcriptionally regulate enhancer of zeste homolog 2 and inhibit migration and invasion in human esophageal squamous cell carcinoma.

BACKGROUND: The enhancer of zeste homolog 2 (EZH2) was found to be overexpressed and associated with tumor metastasis in esophageal squamous cell carcinoma (ESCC). On the other hand, it was reported that miR-26a, miR-98, miR-101, miR-124, miR-138 and miR-214 could inhibit the expression of EZH2 in some tumors. However, the role of miRNAs in the regulation of EZH2 expression in human ESCC has not been documented. The aim of this study was to determine the role of these miRNAs in the regulation of tumor metastasis via EZH2 overexpression in human ESCC. METHODS AND RESULTS: The expression of these miRNAs and EZH2 mRNA were examined by qPCR and the expression of EZH2 protein was detected by western blot. The role of these miRNAs in migration and invasion was studied in ESCC cell line (Eca109) transfected with miRNA mimics or cotransfected with miRNA mimics and pcDNA-EZH2 plasmid (without the 3'-UTR of EZH2). Through clinical investigation, we found that miR-98 and miR-214 expression was significantly lower in ESCC tissues than in matched normal tissues, and the expression level of miR-98 and miR-214 was inversely correlated to EZH2 protein expression and the clinical features such as pathological grade, tumor stage and lymph node metastasis in ESCC. In Eca109 cells, overexpression of miR-98 and miR-214 significantly inhibited the migration and invasion of ESCC cells, which was reversed by transfection of EZH2. CONCLUSIONS: These findings suggest that decreased expression of miR-98 and miR-214 might promote metastasis of human ESCC by inducing accumulation of EZH2 protein.

[Validation and comparison of pharmacogenetics-based warfarin dosing algorithms in Han Chinese patients].

OBJECTIVE: To assess whether the existing three types of pharmacogenetics-based Warfarin dosing algorithms appropriately predict the actual maintenance dose in Han Chinese mechanical heart valve replacement patients (n = 130). METHODS: The patients' CYP2C9 and VKORC1 genetic polymorphisms were detected by PCR-RFLP. The genotype of CYP2C9, VKORC1 and other information were used to calculate predicted doses. Accuracy of the models was assessed using the absolute value of the difference between predicted dose and actual dose, calculated on both an absolute and percentage basis. Actual weekly dose was also regressed on predicted weekly dose, from which we obtained R(2) values. Clinical accuracy of the predictions was assessed by computing the proportion in which the predicted dose was 20% or more below the actual dose (under dosed), within 20% of the actual dose (ideally dosed), or 20% or greater above the actual dose (over dosed). RESULTS: The average absolute error is the smallest for the predictions made by the Wen model (3.74 mg/wk), followed by the Ohno model (4.07 mg/wk) and IWPC model (5.05 mg/wk). R(2) was 40.2% in the Wen model, 38.2% in the Ohno model and 26.7% in the IWPC model. When comparing the percentage of patients for whom the predicted doses were ideal, the Wen model works the best (50.0%) in low-dose group (≤ 21 mg/wk), but the Ohno model works the best (85.29%) in middle-dose group (21 - 49 mg/wk), followed by the Wen model. CONCLUSION: The best accuracy is achieved by the Wen model and the best clinical accuracy is obtained by the Ohno model for predicting the actual maintenance dose in Han Chinese mechanical heart valve replacement patients.

[Effect of γδ T cells on the Proliferation, Apoptosis and Autophagy of Multiple Myeloma Cells].

AbstractObjective: To investigate the effect of γδ T cells on the proliferation, apoptosis and autophagy of multiple myeloma cells. METHODS: Peripheral blood mononuclear cells (PBMNC) were isolated from healthy volunteers, and stimulated with zoledronic acid (Zol) in combination with rhIL-2. Flow cytometry analysis was used to detected the purity of γδ T cells. γδ T cells were collected and co-cultured with RPMI-8226 or U-266 cells at different effector target ratios. The proliferation of RPMI-8226 or U-266 cell lines were detected by CCK-8. Cell cycle and cell apoptosis were detected by flow cytometry and Western blot．The expressions of autophagy-related proteins were detected by Western blot. RESULTS: γδ T cells can be expanded in vitro. γδ T cells could inhibit the proliferation of RPMI-8226 or U-266 cells, induced cell cycle arrest and promoted apoptosis in an effector target-dependent manner. In addition, γδ T cells could induce autophagy of myeloma cells, inhibited the expression of autophagy-related PI3K, P-AKT and P-mTOR, while increased the expression of AMPK and Beclin-1. CONCLUSION: γδ T cells can inhibit the proliferation of RPMI-8226 and U-266 myeloma cells, induce cell cycle arrest, promote apoptosis, and enhance autophagy in vitro. The mechanism may be related to inhibition of PI3K/AKT/mTOR signaling pathway and/or activation of AMPK/Beclin-1 signaling pathway.

MicroRNA-203 inhibits cell proliferation by repressing ΔNp63 expression in human esophageal squamous cell carcinoma.

BACKGROUND: This study was performed to investigate the effect of microRNA-203 (miR-203) and ΔNp63 on cell proliferation and the functional connection between miR-203 and ΔNp63 in ESCC. METHODS: We employed 2 human ESCC cell lines, Eca109 and TE-1, as the model system. The effect of miR-203 and ΔNp63 on cell proliferation was determined in cells transfected with miR-203 mimic and ΔNp63 small interfering RNA (siRNA), respectively. The regulation of ΔNp63 expression in ESCC cells by miR-203 was studied by luciferase reporter assay, RT-PCR and western blot analysis in cells transfected with miR-203. The effect of ΔNp63 re-expression on miR-203 induced inhibition of cell proliferation was studied by cell proliferation assay in cells cotransfected with miR-203 and pcDNA-ΔNp63 plasmid (without the 3'-UTR of ΔNp63). RESULTS: We found that both miR-203 and ΔNp63 siRNA signicantly inhibited cell proliferation in ESCC. MiR-203 could down-regulate endogenous ΔNp63 expression at the posttranscriptional level. Moreover, re-expression of ΔNp63 in cells transfected with miR-203 significantly attenuated the miR-203 induced inhibition of cell proliferation. CONCLUSIONS: Our data implied that miR-203 could inhibit cell proliferation in human ESCC through ΔNp63-mediated signal pathway. Therefore, we propose that miR-203 might be used as a therapeutic agent for human ESCC.

[Research Progress on Regulating Autophagy in the Treatment of Multiple Myeloma --Review].

Abstract　　Autophagy is a process in which cells in eukaryotes degrades abnormal proteins and organelles, thus it possesses important effects on the survival of normal cells and tumor cells. The related studies have shown that autophagy is widely present in the life activities of myeloma cells, which not only protects myeloma cells, but also induces death, and plays an important role in survival, proliferation, invasion and migration of myeloma cells and the treatment of multiple myeloma. This review focuses on the progress of regulating autophagy in the treatment of multiple myeloma.

Synthetic Investigation toward QS-21 Analogues.

With glycosyl o-alkynylbenzotes as donors, a highly efficient protocol to construct the challenging glycosidic linkages at C3-OH of C23-oxo oleanane triterpenoids is disclosed, on the basis of which different strategies for the highly efficient synthesis of QS-21 analogues with the west-wing trisaccharide of QS-21 have been established.

[Genotype Analysis of Pregnant Women with α- and ß- Thalassemia in Fuzhou Area of Fujian Province in China].

OBJECTIVE: To analyze the genotype of pregnant women with α- and ß- thalassemia in Fuzhou area of Fujian province in China. METHODS: Blood routine examination and hemoglobin electrophoresis were performed for pregnant women, and positive samples were examined by gap polymerase chain reaction and reverse dot blot hybridization. RESULTS: 412 cases were diagnosed as α-thalassemia (63.9%); 201 cases were diagnosed as ß-thalassemia (31.2%); 32 cases were diagnosed as α and ß-composite thalassemia. There were 12 genotypes in α-thalassemia, whose major genotypes were --SEA/αα, α3.7/αα, -α4.2/αα and αQSα/αα, with carrying rate of 64.32%, 20.14%, 7.77% and 1.94%, respectively. There were 10 genotypes in ß- thalassemia, whose major genotypes were CD41-42/N, CD17/N, IVS-II-654/N and -28/N, with carrying rate of 30.84%, 27.86%, 15.92% and 10.45%, respectively. There were 9 genotypes in α and ß-composite thalassemia, whose major genotypes were --SEA/αα composited CD41-42/N, -α3.7/αα composited CD41-42/N, --SEA/αα composited CD17/N, with carrying rate of 18.75%, 15.62%, 15.62% respectively. CONCLUSION: The major genotypes of pregnant women with α- and ß- thalassemia in Fuzhou area of Fujian province in China are --SEA/αα, α3.7/αα, CD41-42/N and CD17/N. Thalassemia screening and prenatal gene diagnosis should be strengthened in Fuzhou area of Fujian province in China.

[Effects of Autophagy Regulating Drugs on Proliferation, Apoptosis and Autophagy of Multiple Myeloma Cells].

OBJECTIVE: To investigate the effects of autophagy activator (rapamycin, RAPA) and autophagy inhibitor (hydroxychloroquine, HCQ and 3-methyl adenine, 3-MA) on the proliferation, apoptosis and autophagy of multiple myeloma cell line of RPMI8226. METHODS: RPMI8226 cells were treated with autophagy regulating drugs of different concentrations. The proliferation and apoptosis of cells were determined by CCK-8 and flow cytometry, respectively. The expressions of apoptosis-related proteins BCL-2, caspase-3 and PARP protein were assessed by Western blot. Autophagy was detected by monodansylcadaverine staining. Autophagic protein (LC-3b) and apoptosis-related proteins (caspase-3, PARP and BCL-2) were analyzed by Western blot. RESULTS: RAPA and HCQ inhibited the proliferation of RPMI8226 in a concentration- and time-dependent manner, and increased the apoptosis. However, 3-MA did not show significantly inhibitory effect on the proliferation and apoptosis of RPMI8226. MDC staining showed that the more autophagic vacuoles could be detected in the higher concentration of RAPA, but the less autophagic vacuoles in the higher concentration of HCQ and 3-MA. Western blot showed that RAPA increased the expression of LC3-II/LC3-I, caspase-3 and PARP, but inhibited the expression of BCL-2. HCQ inhibited the expression of LC3-II/LC3-I and BCL-2, but increased the expression of caspase-3 and PARP. 3-MA inhibited the expression of LC3-II/LC3-I, but had no effect on the expression of caspase-3, PARP or BCL-2. CONCLUSION: Rapamycin can inhibit the proliferation, induce apoptosis and autophagy of RPMI 8226, the hydroxychloroquine can inhibit autophagy and proliferation of RPMI 8226, and induce apoptosis, the 3-MA can inhibit autophagy of RPMI 8226, but hardly has any effects on proliferation and apoptosis of RPMI 8226 cells.

[A randomized and case-control clinical study on trimebutine maleate in treating functional dyspepsia coexisting with diarrhea-dominant irritable bowel syndrome].

OBJECTIVE: To observe the efficacy and adverse drug reaction of trimebutine maleate in treating patients with functional dyspepsia (FD) coexisting with diarrhea dominant irritable bowel syndrome (IBS-D). METHODS: 129 patients were enrolled in this randomized, case-control and prospective study and divided into 3 groups. Group A was treated with trimebutine maleate and bacillus licheniformis, Group B with trimebutine maleate and Group C with bacillus licheniformis. The symptoms of the patients were described with grading score and efficacy of treatment assessed according to the changes of grading score of symptoms. RESULTS: There was a significant decrease in the scores of postprandial fullness (4.55 +/- 0.85, 1.26 +/- 0.52; 4.36 +/- 0.66, 1.48 +/- 0.61), early satiation (4.05 +/- 0.96, 1.01 +/- 0.51; 3.89 +/- 0.81, 1.25 +/- 0.76), abdominal pain (9.26 +/- 0.68, 0.68 +/- 0.43; 9.57 +/- 1.60, 0.76 +/- 0.54) and total symptom score (20.00 +/- 1.25, 3.06 +/- 0.91; 19.05 +/- 2.28, 3.89 +/- 2.12) before and after treatment in Group A and B (P < 0.05), but there was no such significance in Group C (P > 0.05). There was a significant decrease in diarrhea score before and after treatment in the 3 groups (A: 4.78 +/- 0.76, 0.65 +/- 0.53; B: 4.13 +/- 0.65, 1.25 +/- 0.62; C: 4.65 +/- 0.88, 1.45 +/- 0.70) (P < 0.05). After treatment for 4 weeks, there was significant difference in the scores of postprandial fullness, early satiation, abdominal pain and total symptom score as well as the effective rate of every symptom and total effective rate between Group A or B and Group C (P < 0.05). The ratio of cost and effect was 4.07, 1.19 and 6.65 in Group A, B and C respectively, the Group B being the best. The rate of adverse drug reaction was 22.9% and 23.7% in Group A and B, and the main adverse drug reactions were mild thirst and constipation. CONCLUSIONS: In treating patients with functional dyspepsia coexisting with diarrhea dominant irritable bowel syndrome, trimebutine maleate has the advantage of high efficacy, low cost and few adverse reactions.

[Observation on the long-term complications after esophageal replacement with colon].

OBJECTIVE: To study the etiology and preventive measures of the long-term postoperative complication after esophageal replacement with colon for esophageal benign disease. METHODS: To review the clinical data of 577 patients with esophageal replacement with colon our department, including 123 cases of esophageal benign disease. Of all, there were 25 cases-time for 11 cases following with severe complication: redundancy and dilated colon 12 cases-time, severe stricture of stoma 4, macrocyst esophagus 2, colon-stomach stoma expansion 4, mechanical obstruction of colon 3. The etiology included iatrogenic and functionality. The therapy included stricture form or resection, redundancy segment resection, obstructed segment solution and stoma resection and form. RESULTS: Eight cases underwent once operation, 2 case twice, 1 case three times. After operation, 9 cases took food normally, 2 improved symptoms obviously. CONCLUSIONS: The iatrogenic and functionality factor contributed to severe complication after esophageal replacement with colon for esophageal benign disease. The preventive measure is followed during operation: cervical esophageal-colon anastomosis exceed 2.5 centimeter, abdominal colon-stomach anastomosis reflux, channel width of colon passage, intestinal canal lay up straight. Re-operation is best choice to for local stricture, colon expansion, redundancy and dilated colon.

[Effect of Complicated Hemophagocytic Syndrome on Clinical Prognosis of Patients with Non-Hodgkin's Lymphoma and Analysis of Its Affecting Factors].

OBJECTIVE: To investigate the effect of complicatal hemophagocytic syndrome on clinical prognosis of patients with non-Hodgkin's lymphoma (NHL) and analyze its factors affecting prognosis. METHODS: Ninety cases of NHL were selected and divided into 2 groups: 61 cases of NHL without hemophagocytic syndrome as group A and 29 cases of NHL with hemophagocytic syndrame as group B. The survival analysis of Kaplan-Meter method and the Cox regression model were used for univariate and multivariate analyses of related factors. RESULTS: The patients in group B were more likely to start with fever, moreover, the hemophagocytes could be found in bone marrow samples of 89.66% (26/29) patients; the levels of total bilirubin, triglycerides, serum ferritin, serum soluble CD25, DNA copies of epstein-barr virus (EBV) and lactate dehydrogenase level in the group B were significantly higher than those in the group A(P<0.05). And the patients in group B had worse physical state, later disease stage, worse disease status and lower overall prognosis as compared with patients in the group A. The complicased hemophagocytic syndrome, incomplete improvemant of deseases state after treatment and EBV infection were the independent risk factors for the poor prognosis of patients with NHL. CONCLUSION: The complicated hemophagocytic syndrome can increase the severity of NHL, there fore significantly influences the clinical prognosis of patients, while the complicated hemophagocytic syndrome, poor therapatic efficacy for patients and EBV infection are independent risk factors affecting the prognosis of NHL patients.

[The effect of recombinant adenovirus encoding antisense MAT1 on cell cycle of human pancreatic cancer cells BxPC-3].

OBJECTIVE: To investigate the regulatory effect of the human MAT1 gene on the cell cycle G(1)/S transition of human pancreatic cancer BxPC-3 cells. METHODS: To construct the replication deficient recombinant adenovirus of antisense MAT1 gene using homologous recombination by AdEasy system. Cell growth assay was carried out by counting alive cells after trypan blue exclusion. The protein expressions of MAT1, cyclin D1, cyclin E, and Rb were detected by western blotting. The cell cycle status was determined by flow cytometry. RESULTS: The recombinant adenovirus encoding antisense MAT1 fragment Ad-MAT1AS was obtained with the titer of expression was 5 x 10(10) pfu/ml. The expression of MAT1 of BxPC-3 was significantly reduced after Ad-MAT1AS infection. In this case BxPC-3 cell cycle was arrested in G(1) phase. The estimated proportion of G(0)/G(1) phase cells in the control for blank and vector cultures ranged from 40% to 44%. In contrast, 79% of the Ad-MAT1AS cells were in G(0)/G(1) phase. Cyclin E and pRb gene expression changes were observed in the infected cells. CONCLUSION: The results suggest that MAT1 gene may play an important role in the regulation of cell cycle G(1)-->S transition of BxPC-3 cells.

Construction of a novel porcine circovirus type 2 infectious clone as a basis for the development of a PCV2 iDNA vaccine.

Porcine circovirus-associated disease is a highly contagious disease that has significant economic consequences. The disease is prevalent in many countries and regions. To generate a genetic marker strain of PCV2, a Sal I restriction enzyme site was inserted into the PCV2 clone as a genetic marker by applying iDNA infectious clone technology. The iDNA represents plasmids that encode the full-length DNA genome of PCV2 assembled in a pcDNA3.1-based vectors. The mutant PCV2 was rescued by transfecting an infectious clone into PK-15 cells and was characterised by an immunoperoxidase monolayer assay (IPMA). The viral genome could be differentiated from the wild-type parent by PCR and restriction fragment length polymorphism (PCR-RFLP). Kunming mice were inoculated with the PCV2 infectious clone or rescued virus via intranasal and intraperitoneal routes. Seroconversion to PCV2-specific antibody appeared in the majority of mice from the two inoculated groups at 7 days postinoculation (DPI), and the specific antibody level was steady for at least 42 days. Viraemia, beginning at 7 DPI and lasting 4 weeks, was detected in the majority of the pigs from the two inoculated groups. The animal experiments revealed that the PCV2 infectious clone and rescued virus both could replicate in mice and induce mice to generate anti-PCV2 antibodies. The infectious clones of PCV2 will be useful for further research investigating a potential tractable iDNA vaccine by reverse genetics technology for attenuated virulance.

Effects of antireflux treatment on bronchial hyper-responsiveness and lung function in asthmatic patients with gastroesophageal reflux disease.

AIM: To investigate the effects of antireflux treatment on bronchial hyper-responsiveness and lung function in asthmatic patients with gastroesophageal reflux disease (GERD). METHODS: Thirty asthmatic patients with GERD were randomly divided into two groups (group A and group B). Patients in group A (n=15) only received asthma medication including inhaled salbutamol 200 microg four times a day and budesonide 400 microg twice a day for 6 weeks. Patients in Group B (n=15) received the same medication as group A, and also antireflux therapy including oral omeprazole 20 mg once a day and domperidone 10 mg three times a day for 6 weeks. Pulmonary function tests and histamine bronchoprovocation test were performed before and after the study. RESULTS: There was no significant difference in the baseline values of pulmonary function and histamine PC(20-FEV1) between the two groups. At the end of the study, the mean values for VC, VC%, FVC, FVC%, FEV(1), FEV(1)%, PEF, PEF%, PC(20-FEV1) were all significantly improved in group B, compared with group A. CONCLUSION: Antireflux therapy may improve pulmonary function and inhibit bronchial hyper-responsiveness in asthmatic patients with GERD.