Interface thermal conductivities induced by van der Waals interactions.

The interface heat transfer of two layers induced by van der Waals (vdW) contacts is theoretically investigated, based on first-principles calculations at low temperatures. The results suggest that out-of-plane acoustic phonons with low frequencies dominate the interface thermal transport due to the vdW interaction. The interface thermal conductivity is proportional to the cubic of temperature at very low temperatures, but becomes linearly proportional to temperature as temperature increases. We show that manipulating the strain alters vdW coupling, leading to increased interfacial thermal conductivity at the interface. Our findings provide valuable insights into the interface heat transport in vdW heterostructures and support further design and optimization of electronic and optoelectronic nanodevices based on vdW contacts.

Substrate dependent terahertz magneto-optical properties of monolayer WS2.

Terahertz (THz) magneto-optical (MO) properties of monolayer (ML) tungsten disulfide (WS2), placed on different substrates and subjected to external magnetic fields, are studied using THz time-domain spectroscopy (TDS). We find that the THz MO conductivity exhibits a nearly linear response in a weak magnetic field, while a distinctly nonlinear/oscillating behavior is found in strong magnetic fields owing to strong substrate-induced random impurity scattering and interactions. The THz MO response of ML WS2 depends sensitively on the choice of the substrates, which we trace back to electronic localization and the impact of the substrates on the Landau level (LL) spectrum. Our results provide an in-depth understanding of the THz MO properties of ML WS2/substrate systems, especially the effect of substrates, which can be utilized to realize atomically thin THz MO nano-devices.

Objective response of first-line chemotherapy of triple-negative breast cancer translates into survival benefit: an analysis in an independent, prospective clinical trial and a real-world setting.

This study sought to assess whether the objective response (OR, including complete response and partial response) of first-line chemotherapy can predict overall survival (OS) for patients with metastatic triple-negative breast cancer (mTNBC) in both clinical trial and a real-world setting. The survival predictable parameters were assessed in two independent cohorts, the training cohort of 236 patients as part of a phase 3 trial (CBCSG006, Trial registration number NCT0128762) and the validation cohort of 360 patients from the real-world setting. Univariable and multivariable Cox proportional hazard models were applied to explore associations with progression-free survival and OS in the training cohort and then in the validation cohort. OR (OR vs non-OR, HR, 0.438, p<0.001) together with Eastern Cooperative Oncology Group (ECOG) performance status, disease-free survival, number of metastatic organ sites and platinum-based chemotherapy used as first-line chemotherapy were observed to be independent prognostic factors for progression-free survival (PFS), and OR (OR vs non-OR, HR, 0.602, p=0.002) together with ECOG score, disease-free survival, number of metastatic organ sites and previous anthracycline and/or taxane treatment were observed to be independent predictive factors for OS in the training cohort. These predictors were confirmed in the validation cohort. For OR and non-OR group, median OS was 23.72 and 13.83 months in the training cohort (HR, 0.637, p=0.002), and 21.95 and 13.80 months in the validation cohort (HR, 0.608, p<0.001), respectively. By adding OR in the OS predictors, the concordance index (C-index) improved from 0.622 to 0.645 in the training cohort and 0.653 to 0.675 in the validation cohort. PFS and OS of mTNBC can be predicted by OR status with any regimen of first-line chemotherapy in an independent prospective clinical trial and a real-world setting. Therefore, TNBC, not like other subtypes of breast cancer, may be in need of combination chemotherapy or intense chemotherapy to achieve a high response rate for survival.

MiR-566 protects the malignant progression of breast cancer by negatively regulating WNT6.

OBJECTIVE: To elucidate the relationship between microRNA-566 (miR-566) and prognosis in breast cancer (BC) and to clarify the influences of miR-566 and WNT6 in its locus region on BC progression. PATIENTS AND METHODS: MiR-566 and WNT6 levels in 44 pairs of BC samples were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The influences of miR-566 on clinical features and prognosis in BC patients were analyzed. According to the differential expressions of miR-566 in the tested BC cell lines, MDA-MB-231 and MCF-7 cells were selected for generating miR-566 knockdown and overexpression models, respectively. Cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) and transwell assays were conducted to explore the role of miR-566 in BC cell functions. Besides, the regulatory interaction between miR-566 and its downstream gene WNT6 was assessed by performing Dual-Luciferase reporter assay. Finally, the co-regulation of miR-566 and WNT6 in BC cell functions was examined. RESULTS: MiR-566 was downregulated in BC tissues. BC patients with a low expression level of miR-566 were prone to suffering a large tumor size, advanced tumor grade, high incidence of lymphatic metastasis and poor prognosis. Overexpression of miR-566 weakened proliferative and migratory abilities in MCF-7 cells, whereas knockdown of miR-566 produced the opposite results in MDA-MB-231 cells. WNT6 was the target gene binding to miR-566, and they displayed a negative expression correlation in BC tissues. Regulatory effects of miR-566 on BC progression could be reversed by WNT6. CONCLUSIONS: MiR-566 is closely related to tumor size, tumor grade, lymphatic metastasis and prognosis in BC. It protects the malignant progression of BC by negatively regulating WNT6.

Coupled plasmon-phonon modes in monolayer MoS2.

We present a theoretical study of the plasmon-phonon coupling in a suspended monolayer MoS2 and a MoS2 substrate system using a diagrammatic self-consistent field theory. The four coupled plasmon-phonon modes and the four plasmon-surface phonon modes are observed due to the spin-orbit and electron-optic phonon interactions. The two of coupled plasmon-phonon and plasmon-surface phonon modes are optic-like and the other two are acoustic-like. The plasmon are strongly coupled with the optic-phonon in MoS2 and the surface optic-phonon in the substrates as the electron density or wave-vector increases. The strong plasmon-phonon coupling shows that the optoelectronic properties of monolayer MoS2 are evidently modulated by electron-phonon interactions. The hybrid plasmon-phonon polaritons can be achieved by strong light-mater interactions. This study is relevant to the application of MoS2 as novel plasmonic and nanophotonic devices.

Biomarker assessment of the CBCSG006 trial: a randomized phase III trial of cisplatin plus gemcitabine compared with paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer.

Background: CBCSG006 trial reported the superior efficacy of cisplatin plus gemcitabine (GP) regimen than paclitaxel plus gemcitabine (GT) regimen as first-line treatment of metastatic triple-negative breast cancer (mTNBC). This study focused on the updated survival data and the explorations of potential biomarkers for efficacy. Patients and methods: Germ-line mutations of homologous recombination (HR) panel, BRCA1/2 included, were evaluated in 55.9% (132/236) patients. PD-L1 expression was evaluated in 48.3% (114/236) patients. A nonparametric sliding-window subpopulation treatment effect pattern plot (STEPP) methodology was used to analyze the absolute survival benefits. All statistical tests were two-sided. Results: Median progression-free survival (PFS) was 7.73 [95% confidence interval (CI) 6.46-9.00] months for GP arm and 6.07 (95% CI 5.32-6.83) months for GT arm (P = 0.005). No significant difference in overall survival (OS) was observed. There was significant interaction between HR status and treatment for PFS and status of HR deficient significantly correlated with higher objective response rate (ORR) and longer PFS in GP arm than in GT arm (71.9% versus 38.7%, P = 0.008; 10.37 versus 4.30 months, P = 0.011). There was no significant interaction between germ-line BRCA1/2 (gBRCA1/2) status and treatment for PFS. Patients with gBRCA1/2 mutation had numerically higher ORR and prolonged PFS in GP arm than in GT arm (83.3% versus 37.5%, P = 0.086; 8.90 versus 3.20 months, P = 0.459). There was no significant interaction between PD-L1 status and treatment for PFS, and no significant differences in ORR, PFS or OS between two arms regardless of PD-L1 status. In STEPP analysis, patients with lower composite risks had more absolute benefits in PFS than those with higher composite risks. Conclusions: GP regimen has superior efficacy than GT regimen as first-line chemotherapy for mTNBC patients. Germ-line mutations of BRCA1/2 and HR panel are possible biomarkers for better performance of cisplatin-based regimens. A composite risk model was developed to guide patient selection for GP treatment in TNBC patients. Trial registration: ClinicalTrials.gov, NCT01287624.

Relationship between CYP17 gene polymorphisms and risk of prostate cancer.

Cytochrome P450 17a-hydroxylase (CYP17) plays a critical role in androgen biosynthesis. Polymorphisms of the CYP17 promoter have been proposed as risk factors for prostate cancer; however, some studies have produced inconclusive or controversial results. We investigated the relationship between polymorphisms of the CYP17 gene and the risk of prostate cancer. A total of 176 patients with prostate cancer were enrolled in the study, and 168 healthy individuals acted as the control group. The participants were divided into those <71 years old and those ≥71 years old. Restriction fragment length polymorphism-polymerase chain reaction was used to confirm the genotype of CYP17 in the samples. The prostate-specific antigen (PSA) concentrations were also measured in all subjects. When T/C and C/C were compared with T/T, the ORs were 0.478 (P = 0.489) and 0.814 (P = 0.367), respectively. There was no significant difference in PSA concentration among the three genotypes in the <71 group, whereas there were statistically significant differences in the ≥71 group (P = 0.003 and 0.012, respectively). There was no significant difference in free PSA and total PSA levels between the three groups and the control group. The T/C and C/C genotypes were not associated with the risk of prostate cancer, and there were no significant differences between them. In the ≥71 group, the T/C and C/C genotypes were closely associated with prostate cancer, which suggests that the CYP17 gene might be a risk factor for prostate cancer in males of advanced age.

Construction of a hepatocellular carcinoma cell line that stably expresses stathmin with a Ser25 phosphorylation site mutation.

We constructed hepatocellular carcinoma (HCC) cells that stably express stathmin with a Ser25 phosphorylation site mutation (stathmin S25A). We used the polymerase chain reaction for site-directed mutagenesis, constructed a stathmin S25A plasmid, and verified the results by restriction enzyme cleavage and sequencing technology. Using the liposome transfection method, stathmin wild-type and S25A HCCLM6 cells were established, which were identified by western blotting. The sequencing report of the stathmin S25A plasmid showed that stathmin serine at position 25 had mutated into alanine. Stable cells transfected with stathmin wild-type and S25A plasmids were constructed. Using western blotting, we confirmed that the expression level of stathmin pS25 in the stathmin S25A cells was reduced than that in the stathmin wild-type and HCCLM6 control cells (P < 0.05). We constructed stathmin S25A HCCLM6 cells, which offer an experimental model for further investigation of the molecular mechanism of stathmin phosphorylation in hepatocarcinogenesis.

Effect of leukocyte filtration on the P-selectin expression of apheresis platelets.

The aim of this study was to investigate the effect of leukocyte filtration on the P-selectin (CD62P) surface expression of apheresis platelets during the retention period. Ten bags of apheresis platelets stored for 1 day (0-24 h) and 10 bags of apheresis platelets stored for 2 days (24-48 h) were used for leukocyte filtration (experimental group). Ten bags of apheresis platelets with the corresponding retention periods but without filtration were used as a negative control (control group). Thereafter, 100 µL of platelet suspensions from apheresis platelets with or without leukocyte filtration were sampled before and after leukocyte filtration for the detection of CD62P surface expression by flow cytometry. No statistical difference in the CD62P surface expression of apheresis platelets was observed before and after leukocyte filtration (P > 0.05), neither did the CD62P surface expression exhibit any change among the different retention periods. Leukocyte filtration does not affect the CD62P surface expression of apheresis platelets stored for up to 2 days, which indicates that leukocyte filtration does not damage the activation of apheresis platelets within the retention period.

Identification of EeSt-genome species in Pseudoroegneria and Elytrigia (Poaceae: Triticeae) by using SCAR markers from ITS sequences.

To detect E(e)St-genome species in Pseudoroegneria and Elytrigia, the primers ES45 (5'-GTAGGCGACGGTTTTCA-3') and ES261 (5'-TCGCTACGTTCTTCATC-3') were designed as sequence characterized amplified region markers based on the 6-base pair indel in internal transcribed spacer 1 (ITS1) regions and conserved sites in the 5.8S regions, respectively. Polymerase chain reaction of ITS fragments in 27 Triticeae accessions was used for amplification with a touchdown thermocycling profile. Two amplicons were purified, sequenced, and aligned. The results indicated that: 1) primers ES45 and ES261 generated the expected products, 2) ITS sequences of E(e)St-genome species are characterized by a 6-base pair indel, and 3) 13 taxa in Pseudoroegneria and Elytrigia should be included in Trichopyrum. The primers ES45 and ES261 were useful for detecting ITS fragments with 6-bp indel and are helpful for clarifying taxonomic classifications of EeSt-genome species in Triticeae.

Evaluation of recombinant chitinase and SXP1 antigens as antimicrofilarial vaccines.

Prior studies indicate that a microfilarial stage-specific chitinase is a possible candidate antigen for a transmission-blocking vaccine against Brugian filariasis. The antigen is a functional enzyme that progressively appears as microfilariae mature and become able to infect and develop in a susceptible mosquito vector. It is recognized by a monoclonal antibody that reduces microfilaremia in infected animals and by a subset of sera from infected persons who remain amicrofilaremic. Immunization of jirds with recombinant chitinase induced partial protection against microfilaremia resulting from subsequent infection with Brugia malayi, but did not reduce adult worm burdens. Vaccination was much less effective when administered during the prepatent stage of infection and was ineffective when given to microfilaremic jirds. The protective epitope appears to be located close to the carboxy terminus of the chitinase molecule. Immunization of jirds with SXP1, an antigen present in multiple worm stages, also reduced microfilaremia and, in some experiments, adult worm burdens, but hyperimmunization with a recombinant filarial myosin was not protective. These observations indicate that the relative timing of immunization and infection is an important factor in the efficacy of antimicrofilarial vaccines.

[Efficacy of ivermectin for control of microfilaremia recurring after treatment with diethylcarbamazine: immunological observation].

We compared the effect of a single dose of ivermectin (100 micrograms/kg) with that of a standard course of diethylcarbamazine (DEC) (6 mg/kg) on several parameters of the host's antifilarial immune response in 60 patients with bancroftian filariasis enrolled in a double-blind drug trial. All participants had measurable serum levels of antifilarial antibodies and parasite antigens. Drug-induced clearance of microfilaremia was associated with a temporary increase in HC11 antigenemia and a decrease in serum levels of antibodies to soluble filarial antigens. Antigenemia progressively declined in patients who remained a microfilaremic after treatment, but declined and then rose in persons with recurrent microfilaremia. Treatment triggered a sustained increase in serum levels of IL-1, IL-6, TNF alpha and IFN gamma in all patients. Although Ivermectin and DEC are believed to exert their antiparasite activity via different mechanisms, the same pattern of serological changes was observed in patients treated with either drug.

[Efficacy of ivermectin for control of microfilaremia recurring after treatment with diethylcarbamazine. I. Clinical and parasitological observations].

We compared the efficacy of a single dose of ivermectin with that of a standard course of deithylcarbamazine (DEC) for the control of microfilaremia in 60 patients with banrroftian filariasis who had developed recurrent microfilaremia after each of three or more prior treatments with DEC. The study was done as a randomized, double-blind trial. Complete, but transient clearance of microfilaremia was observed in both treatment groups. One year later, recurrent microfilaremia was present in 7 patients treated with ivermectin and in 5 treated with DEC. Pretreatment levels of microfilaremia were significantly higher in patients who relapsed within one year after treatment than in those who remained amicrofilaremia. Side effects of either treatment were common but mild. Febrile reactions were more frequent in the ivermectin group: while localized reactions consistent with a flare up of acute filarial disease occurred mostly in the DEC group. We conclude that ivermectin is an effective and practical alternative to DEC for treatment of recurrent microfilaremia due to bancroftian filariasis.

Efficacy of ivermectin for control of microfilaremia recurring after treatment with diethylcarbamazine. I. Clinical and parasitologic observations.

We compared the efficacy of a single dose of ivermectin with that of a standard course of diethylcarbamazine (DEC) for the control of microfilaremia in 60 patients with bancroftian filariasis who had developed recurrent microfilaremia after each of three or more prior treatments with DEC. The study was done as a randomized, double-blind trial. Complete, but in some cases, transient clearance of microfilaremia was observed in both treatment groups. At one year, recurrent microfilaremia was present in seven patients treated with ivermectin and in five treated with DEC. Pretreatment levels of microfilaremia were significantly higher in patients who relapsed within one year after treatment than in those who remained amicrofilaremic. Side effects with both treatments were common, but mild. Febrile reactions were more frequent in the ivermectin group; localized reactions consistent with a flare-up of acute filarial disease occurred mostly in the DEC group. We conclude that ivermectin is an effective and practical alternative to DEC for treatment of recurrent microfilaremia due to bancroftian filariasis.

Efficacy of ivermectin for control of microfilaremia recurring after treatment with diethylcarbamazine. II. Immunologic changes following treatment.

We compared the effect of a single dose of ivermectin with that of a standard course of diethylcarbamazine (DEC) on several parameters of the host's antifilarial immune response in 60 patients with bancroftian filariasis enrolled in a double-blind drug trial. All participants had measurable serum levels of antifilarial antibodies and parasite antigens at the onset of the study. Drug-induced clearance of microfilaremia was associated with a temporary increase in HC 11 antigenemia and a decrease in serum levels of antibodies to soluble filarial antigens. Antigenemia progressively declined in patients who remained amicrofilaremic after treatment, but declined and then increased in persons with recurrent microfilaremia. Treatment triggered a sustained increase in serum levels of interleukin-1, tumor necrosis factor, and interleukin-6 in all patients studied. Although ivermectin and DEC are believed to exert their antiparasite activity via different mechanisms, the same pattern of serologic changes was observed in patients treated with either drug.

Monitoring of filarial antigens in jirds and patients after treatment.

We developed a sandwich ELISA with monoclonal antibodies to monitor filarial antigens in animals and patients after infection and treatment. Levels of antimicrofilarial antibodies and parasite antigens were measured periodically in 40 B. malayi infected jirds. In all animals L3 HC11 antigen was detected earlier than Mf ES34 antigen, while antimicrofilarial antibodies appeared much more slowly. These serologic changes precede the onset of patent infections. After 3 courses of treatment with DEC and M170, the levels of parasite antigen in sera and of Mf in peritoneal cavities were monitored in 23 infected jirds. In 8 jirds Mf became negative, no adult worms were found in 7 jirds and a single degenerating female worm was present in 1 jird. ES34 and HC11 were undetectable in 8/8 and 6/8 necropsy sera. Mf persisted in 11 animals, 9 jirds were necropsied, 8 contained adult worms. Detectable levels of ES34 or HC11 antigen were present in 7/9 and 8/9 from these animals. In sham-treatment, few changes were noted in control animals. Thus, parasitological findings at necropsy are correlated with the results of antigen detection assay. We analyzed serial serum samples from 32 bancroftian microfilaremia collected 1-42 months after DEC therapy. Mf resolved rapidly in all treated individuals. ES34 disappeared faster than HC11, 3 months after treatment. Levels of ES34 and HC11 antigens remained detectable or rising after treatment in 8 and 10 individuals. Four patients' Mf recurred 20-42 months after treatment. These findings show that the remaining or a rise in serum levels of antigen after therapy predicts recurrent microfilaremia in patients and additional treatment is needed.

Parasite antigenemia in untreated and treated lymphatic filarial infections.

To evaluate the merit of antigen detection assays as a tool to monitor the efficacy of chemotherapy for lymphatic filariasis, we serially measured antigen levels in sera from jirds infected with Brugia malayi and from humans with bancroftian filariasis. Antigenemia was detected in all animals with parasitologically proven infection and was present in jirds with prepatent or occult filariasis. Antigen levels correlated with worm burdens, and progressively declined in drug-cured animals. Treatment with diethylcarbamazine (DEC) triggered a transient increase in serum levels of filarial antigens bearing the epitope recognized by the monoclonal antibody HC 11. All patients with bancroftian filariasis became amicrofilaremic within one week after DEC treatment. Antigenemia levels slowly declined over a period of several months in all but one treated individual. Forty-two months after treatment, progressively rising antigen levels are present in 10 patients. Six of these remain amicrofilaremic; in the other 4, elevated antigenemia levels preceded or were detected at the same time as recurrent parasitemia. Periodic monitoring of antigenemia levels after treatment of patients with lymphatic filariasis can be used to identify individuals who are likely to develop recurrent microfilaremia before the parasites become detectable in blood samples, thereby allowing timely retreatment.

Comparison of Dot-ELISA with Sandwich-ELISA for the detection of circulating antigens in patients with bancroftian filariasis.

We compared the performance of a newly developed Dot-ELISA with that of a previously described Sandwich-ELISA to detect parasite antigens in sera from patients with bancroftian filariasis. The same monoclonal antibody and the same sera were used in both tests. In the Dot-ELISA, 67 of 70 sera from microfilaremic donors were deemed to contain filarial antigens when screened at a dilution of 1:50. End titers were 1:80-1:1280. With the Sandwich-ELISA, 64 of the same sera were positive at a dilution of 1:10 and 42 were positive at a dilution of 1:50. End titers were 1:10-1:320. The specificity of both assays was greater than 95%, but their sensitivity was remarkably different. The Dot-ELISA could detect as little as 0.055 ng/ml microfilarial antigen added to normal human sera, whereas the lower limit with the Sandwich-ELISA was 10 ng/ml parasite antigen. Additionally, the Dot-ELISA does not require radioactivity or sophisticated equipment and, therefore, can be performed in virtually all filariasis-endemic areas.