Zimberelimab plus chemotherapy as the first-line treatment of malignant peritoneal mesothelioma: A case report and review of literature.

BACKGROUND: Malignant peritoneal mesothelioma (MPeM) is a rare cancer with a poor prognosis at advanced stage, and the standard first-line treatment for inoperable patients is chemotherapy. Although combining programmed cell death 1 (PD-1) inhibitors with chemotherapy is generally considered safe and effective in several malignant solid tumors, there are few reports regarding initial immunochemotherapy in advanced MPeM. CASE SUMMARY: Here, to our knowledge, we present the first case of a patient with epithelioid subtype MPeM, who was treatment-naïve and benefited from initial PD-1 inhibitor plus standard chemotherapy with a prolonged progression-free survival (PFS) and good tolerance. A 49-year-old man was admitted to our hospital for a persistent burning sensation in the abdomen. Computed tomography revealed a solid mass in the lower abdomen, which was subsequently diagnosed histologically as epithelioid subtype MPeM by core needle biopsy. The patient received eight cycles of pemetrexed 800 mg (day 1), cisplatin 60/50 mg (day 1-2), and zimberelimab (PD-1 inhibitor) 240 mg (day 1) every 3 wk. He achieved significant reduction of peritoneal tumors with remarkable improvement in symptoms. The best tumor response was partial remission with a final PFS of 7 mo. No immune-related adverse event occurred during the combination treatment. CONCLUSION: The outcome of the present case demonstrates the promising anti-tumor activity of immunochemotherapy to treat inoperable MPeM in the future.

Pr3+-doped CeF3 crystals: Analysis of optical traits and fluorescence from Pr3+: 1D2 level for visible and near-infrared lasers.

In this work, four Pr3+ -doped CeF3 crystals with 0.2, 0.4, 0.6, and 0.8 at.% Pr3+ ion doping levels nominally in the melt have been successfully grown, and their absorption and emission spectra, including fluorescence decay times were analyzed. Especially, yellow and near-infrared (NIR) emissions originating from Pr3+: 1D2 level were explored in detail. In comparison, 0.2 at.% Pr3+-doped sample showed better spectral parameters in all studied crystals. In such a crystal, at 443 nm wavelength, the derived absorption cross-section (σabs) is 0.88 × 10-20 cm2 with full width at half maximum (FWHM) âˆ¼ 10 nm in π polarization direction, whereas σabs is 1.32 × 10-20 cm2 with FWHM âˆ¼ 6.7 nm in σ polarization direction at the same wavelength. Likewise, the calculated emission cross-section (σem) for 594 nm wavelength is 0.69 × 10-20 cm2 in π direction and 0.46 × 10-20 cm2 in σ direction. Also, acquired σem at 790, 755, 1014, and 1432 nm wavelengths is 6.15 × 10-21 cm2, 7.33 × 10-21 cm2, 7.66 × 10-21 cm2, and 6.56 × 10-21 cm2 individually. Here evaluated fluorescence decay time of 1D2 level is âˆ¼ 200.6 µs. Obtained higher σabs, larger σem, and higher luminescence decay rates of 0.2 at.% Pr: CeF3 crystal specify its potential as a gain medium for orange and NIR lasers.

Overexpression of Activating Transcription Factor-2 (ATF-2) Activates Wnt/Ca2+ Signaling Pathways and Promotes Proliferation and Invasion in Non-Small-Cell Lung Cancer.

Previous studies have suggested an association of the expression of activating transcription factor-2 (ATF-2) with the survival time and the activity of the Wnt/Ca2+ signaling pathway in non-small-cell lung cancer (NSCLC). However, the exact role of ATF-2 in tumorigenesis and its underlying mechanism remains unclear. In this study, we study whether ATF-2 regulates the growth and reproduction of NSCLC cells through the Wnt/Ca2+ pathway. The expression of ATF-2 and pathway-related genes in non-small-cell lung cancer was detected by qRT-PCR and Western blotting. CRISPR/Cas9 technology was used to knock out the ATF-2 gene, and pathway inhibitors and agonists were added to induce cultured cells. The expression of pathway genes and the proliferation and invasion ability of A549 lung cancer cells were analyzed. ATF-2 and pathway-related genes were upregulated in NSCLC. The proliferation and invasion ability of A549 lung cancer cells was decreased after only adding pathway inhibitors. The expression of Wnt/Ca2+ pathway protein was decreased when the ATF-2 gene was knocked out, but the expression of Wnt/Ca2+ pathway protein was reversed after the addition of a pathway agonist. These results suggest that ATF-2 acts as an agonist in the Wnt/Ca2+ signaling pathway, promoting the expression of Wnt5a, Wnt11, CaMK II, and NLK in the Wnt/Ca2+ pathway, thereby regulating the proliferation and invasion of NSCLC cells.

P53 suppresses the progression of hepatocellular carcinoma via miR-15a by decreasing OGT expression and EZH2 stabilization.

Existing literature has highlighted the tumour suppressive capacity of microRNA-15a (miR-15a); however, its role in hepatocellular carcinoma (HCC) remains relatively unknown. This study aimed to investigate the role of miR-15a in HCC and the associated underlying mechanism. Initially, RT-qPCR was performed to detect the expression of miR-15a in HCC tissues and cells. Bioinformatics analysis, Pearson correlation coefficient, dual-luciferase reporter assay, and molecular approaches were all conducted to ascertain the interaction between miR-15a and O-linked N-acetylglucosamine (GlcNAc) transferase (OGT). PUGNAc treatment and cycloheximide (CHX) assay were performed to evaluate O-GlcNAc and the stabilization of the enhancer of zeste homolog 2 (EZH2). Finally, gain- and loss-of-function studies were employed to elucidate the role of P53 and the miR-15a/OGT/EZH2 axis in the progression of HCC, followed by in vivo experiments based on tumour-bearing nude mice. Our results demonstrated that the miR-15a expression was decreased in the HCC tissues and cells. P53 upregulated miR-15a expression, which inhibited the proliferation, migration and invasion of HCC cells, while inducing apoptosis and triggering a G0/G1 cell cycle phase arrest. OGT stabilized EZH2 via catalysing O-GlcNAc, which reversed the effect of P53 and miR-15a. The results of our in vivo study provided evidence demonstrating that P53 could suppress the development of HCC via the miR-15a/OGT/EZH2 axis. P53 was found to inhibit the OGT expression by promoting the expression of miR-15a, which destabilized EZH2 and suppressed the development of HCC. The key findings of our study highlight a promising novel therapeutic strategy for the treatment of HCC.

Donafenib Versus Sorafenib in First-Line Treatment of Unresectable or Metastatic Hepatocellular Carcinoma: A Randomized, Open-Label, Parallel-Controlled Phase II-III Trial.

PURPOSE: Donafenib, a novel multikinase inhibitor and a deuterated sorafenib derivative, has shown efficacy in phase Ia and Ib hepatocellular carcinoma (HCC) studies. This study compared the efficacy and safety of donafenib versus sorafenib as first-line therapy for advanced HCC. PATIENTS AND METHODS: This open-label, randomized, parallel-controlled, multicenter phase II-III trial enrolled patients with unresectable or metastatic HCC, a Child-Pugh score ≤ 7, and no prior systemic therapy from 37 sites across China. Patients were randomly assigned (1:1) to receive oral donafenib (0.2 g) or sorafenib (0.4 g) twice daily until intolerable toxicity or disease progression. The primary end point was overall survival (OS), tested for noninferiority and superiority. Efficacy was primarily assessed in the full analysis set (FAS), and safety was assessed in all treated patients. RESULTS: Between March 21, 2016, and April 16, 2018, 668 patients (intention-to-treat) were randomly assigned to donafenib and sorafenib treatment arms; the FAS included 328 and 331 patients, respectively. Median OS was significantly longer with donafenib than sorafenib treatment (FAS; 12.1 v 10.3 months; hazard ratio, 0.831; 95% CI, 0.699 to 0.988; P = .0245); donafenib also exhibited superior OS outcomes versus sorafenib in the intention-to-treat population. The median progression-free survival was 3.7 v 3.6 months (P = .0570). The objective response rate was 4.6% v 2.7% (P = .2448), and the disease control rate was 30.8% v 28.7% (FAS; P = .5532). Drug-related grade ≥ 3 adverse events occurred in significantly fewer patients receiving donafenib than sorafenib (125 [38%] v 165 [50%]; P = .0018). CONCLUSION: Donafenib showed superiority over sorafenib in improving OS and has favorable safety and tolerability in Chinese patients with advanced HCC, showing promise as a potential first-line monotherapy for these patients.

Spectral analyses of Dy3+/Sr2+: LaF3 and Dy3+/Ca2+: LaF3 mixed crystals for laser applications.

Mixed crystals of Dy3+/Sr2+: LaF3 and Dy3+/Ca2+: LaF3 were grown by Bridgman technique and their spectral properties were investigated. Spectra broadening and peak shifts were observed, indicating the co-doping of Sr2+/Ca2+ brings about a more disordered local symmetry of Dy3+, which makes both crystals favorable for tunable lasing action. Low-temperature high resolution excitation and emission spectra were carried out for exploring the types of luminescent center of Dy3+ in crystals. Room-temperature absorption and emission spectra, together with the fluorescence decay curves were studied in both crystals for estimating their potentials for yellow and MIR lasers. Under 450 nm excitation, the largest emission cross-sections at 571 nm of 1.51 × 10-21 cm2 for Dy3+/Sr2+: LaF3 crystal and 1.56 × 10-21 cm2 for Dy3+/Ca2+: LaF3 crystal, along with the lifetimes of Dy3+: 4F9/2 level as 0.983 ms for Dy3+/Sr2+: LaF3 crystal, 1.143 ms for Dy3+/Ca2+: LaF3 crystal were obtained, respectively. Besides yellow emissions, MIR emissions approximately at 3 µm are more appealing. Under 1280 nm excitation, the largest emission cross-sections of 0.304 × 10-20 cm2 at 2885 nm in Dy3+/Sr2+: LaF3 crystal, and 0.319 × 10-20 cm2 at 2880 nm in Dy3+/Ca2+: LaF3 crystal, together with rather long lifetimes of Dy3+: 6H13/2 in the level of milliseconds were achieved, making them useful media for MIR lasers.

Universal SMP gripper with massive and selective capabilities for multiscaled, arbitrarily shaped objects.

Grippers are widely used for the gripping, manipulation, and assembly of objects with a wide range of scales, shapes, and quantities in research, industry, and our daily lives. A simple yet universal solution is very challenging. Here, we manage to address this challenge utilizing a simple shape memory polymer (SMP) block. The embedding of objects into the SMP enables the gripping while the shape recovery upon stimulation facilitates the releasing. Systematic studies show that friction, suction, and interlocking effects dominate the grip force individually or collectively. This universal SMP gripper design provides a versatile solution to grip and manipulate multiscaled (from centimeter scale down to 10-µm scale) 3D objects with arbitrary shapes, in individual, deterministic, or massive, selective ways. These extraordinary capabilities are demonstrated by the gripping and manipulation of macroscaled objects, mesoscaled steel sphere arrays and microparticles, and the selective and patterned transfer printing of micro light-emitting diodes.

Silencing of long noncoding RNA SRRM2-AS exerts suppressive effects on angiogenesis in nasopharyngeal carcinoma via activating MYLK-mediated cGMP-PKG signaling pathway.

Long noncoding RNAs (lncRNAs) play a crucial role in several malignances, involving nasopharyngeal carcinoma (NPC), a heterogeneous disease. This study investigated mechanism of serine/arginine repetitive matrix protein 2-alternative splicing (SRRM2-AS) in NPC cell proliferation, differentiation, and angiogenesis. Initially, differentially expressed lncRNAs were screened out via microarray analysis. Vascular endothelial growth factor (VEGF) protein positive rate and microvessel density (MVD) were determined in NPC and adjacent tissues. NPC CNE-2 cells were treated with a series of vector and small interfering RNA to explore the effect of SRRM2-AS in NPC. The target relationship between myosin light chain kinase (MYLK) and SRRM2-AS was verified. Levels of SRRM2-AS, MYLK, cGMP, PKG, VEGF, PCNA, Ki-67, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and Caspase 3 were determined after transfection. Finally, the effect of SRRM2-AS on cell proliferation, colony formation, angiogenesis, cell cycle, and apoptosis in NPC was evaluated. SRRM2-AS was highly expressed and MYLK was poorly expressed in NPC tissues. VEGF protein positive rate and MVD were elevated in NPC tissues. MYLK was confirmed to be a target gene of SRRM2-AS. Silencing of SRRM2-AS elevated levels of MYLK, cGMP, PKG, Bax, and Caspase 3, but decreased levels of VEGF, PCNA, Ki-67, and Bcl-2. Especially, silencing of SRRM2-AS suppressed cell proliferation, colony formation and angiogenesis, blocked cell cycle, and enhanced cell apoptosis in NPC. Our results suggested that silencing of SRRM2-AS protected against angiogenesis of NPC cells by upregulating MYLK and activating the cGMP-PKG signaling pathway, which provides a new target for NPC treatment.

Spectroscopic properties analyses and laser characterization simulation of Er3+,Eu3+:YAP single crystal.

Er,Eu:YAlO3 (abbr. as Er,Eu:YAP) crystal was grown by the Czochralski technique for the first time. Its absorption and fluorescence spectra as well as the fluorescence decay curves were measured and investigated. The spectral parameters including absorption cross-section and emission cross-section were calculated. It is found that the crystal has short lifetimes at 4I13/2 and 4I11/2 levels, large absorption cross-section at 974 nm and 790 nm, and large stimulated emission cross-section at 2704 nm. The co-dopant Eu3+ decreases the fluorescence lifetime of 4I11/2 level from 400 µs to 59.35 µs, and thus inhibits the self-termination effect of ~2.7 µm in some degree. We develop a theoretical model that simulates the laser characteristics of Er,Eu:YAP crystal numerically. Based on Er3+-Eu3+ energy level diagrams, the rate equation model was built and discussed. It was found that: when the pump rate increases gradually, the laser quantum efficiency reaches to its upper limit with a fixed value 2-p2, and this value is 1.35 for Er,Eu:YAP crystal. The results show that Er,Eu:YAP crystal is an excellent material candidate for ~2.7 µm laser.

Nicotinamide N-methyltransferase enhances the progression of prostate cancer by stabilizing sirtuin 1.

A previous study demonstrated that nicotinamide N-methyltransferase (NNMT) is upregulated in the tissues of patients with prostate cancer (PCa); however, the specific underlying mechanism of this remains unclear. To begin with, the expression of NNMT was investigated in the peripheral blood of patients with PCa and of healthy control subjects. The results indicated that the expression level of NNMT was elevated in the peripheral blood and tissues of patients with PCa. Furthermore, the overexpression of NNMT enhanced PC-3 cell viability, invasion and migration capacity. Additionally, the overexpression of NNMT significantly increased the mRNA level of sirtuin 1 (SIRT1) in PC-3 cells. In addition, nicotinamide treatment significantly suppressed the expression of SIRT1 even in PC-3 cells transfected with adeno-associated virus-NNMT. Furthermore, the PC-3 cell invasion capacity was notably decreased by the nicotinamide treatment; however, such effects were largely abolished by the overexpression of NNMT in PC-3 cells. These data indicated that NNMT enhanced PC-3 cell migration and invasion mainly by regulating SIRT1 expression. In summary, the present study indicated that NNMT is an important regulator of SIRT1 expression in PC-3 cells and may be a potential therapeutic target for PCa.

Crystal growth, structure and characterization of Er6B4O15 as self-activated eye-safe laser material within the near-infrared waveband.

A new rare-earth borate Er6B4O15 was synthesized by a solid-state reaction technique. The crystal was obtained by a flux method. Single-crystal X-ray diffraction analysis revealed that the crystal structure is composed of ErO6 polyhedra sharing edges and BO3 groups. The absorption, near-infrared fluorescence spectra and the fluorescence decay curve of Er: 4I13/2 energy level in the Er6B4O15 crystal were measured at room temperature. The absorption peak was located at 977 nm with absorption cross section of 1.16 × 10-21 cm2 and a full width at half-maximum (FWHM) of 16 nm, which is very suitable for commercial 980 nm laser diode pumping. A maximum emission peak at 1560 mm with a broad FWHM of 64 nm was observed in this crystal because of the Er3+ transition 4I13/2→4I15/2, while the emission cross section was calculated to be 8.53 × 10-20 cm2. These results imply that the Er6B4O15 crystal is a promising candidate material for the achievement of an eye-safe near-infrared wavelength laser.

High performance of a passively Q-switched mid-infrared laser with Bi2Te3/graphene composite SA.

We report passively Q-switched ∼2 and ∼3 µm mid-infrared (MIR) solid-state lasers with a self-assembly solvothermal-synthesized Bi2Te3/graphene heterostructure saturable absorber (SA) for the first time. Based on the oxidation resistance and high thermal conductivity of graphene, and large modulation depth of Bi2Te3 nanosheets, two high-performance Q-switching lasers were realized. One is a Tm:YAP laser with a maximum average output power of 2.34 W and a pulse width of 238 ns at ∼2 µm. The corresponding maximum pulse peak power was 91 W, which was much improved in comparison with the pure graphene-based Tm laser. The other one is an Er:YSGG laser producing a pulse width of 243 ns, which is the shortest among the 2D SAs-based ∼3 µm solid-state lasers, as far as we know. Our results indicate that such a composite Bi2Te3/graphene material is a promising SA for generating high-performance mid-infrared pulse lasers.

Activating transcription factor 2 expression mediates cell proliferation and is associated with poor prognosis in human non-small cell lung carcinoma.

Activating transcription factor 2 (ATF2) is a member of the cAMP response element binding protein family that heterodimerizes and activates other transcription factors involved in stress and DNA damage responses, growth, differentiation and apoptosis. ATF2 has been investigated as a potential carcinogenic biomarker in certain types of cancer, such as melanoma. However, its function and clinical significance in non-small cell lung cancer (NSCLC) has not been well studied. Therefore, the present study aimed to analyze the association between ATF2/phosphorylated (p)-ATF2 expression and NSCLC malignant behavior, and discuss its clinical significance. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect the expression of ATF2 in NSCLC cell lines and fresh NSCLC tissue samples. In addition, immunohistochemistry (IHC) was performed to identify the location and expression of ATF2 and p-ATF2 (threonine 71) in paraffin-embedded sections of NSCLC and adjacent normal tissue. The results demonstrated that ATF2 was markedly overexpressed in the NSCLC cells and significantly overexpressed in the fresh NSCLC tissues compared with the control cells and samples (86 paraffin-embedded tissue sections), respectively (P<0.01). Further data demonstrated that ATF2 expression levels were significantly increased in tumor tissues compared to normal tissues and ATF2 was located in the cytoplasm and nucleus. ATF2 expression was closely associated with adverse clinical characteristics such as TNM stage (P=0.002), tumor size (P=0.018) and metastasis (P=0.027). In addition, nuclear p-ATF2 staining was positive in 65/86 samples of NSCLC. Furthermore, the Kaplan-Meier analysis indicated that patients with high levels of ATF2 and p-ATF2 expression had a significantly shorter overall survival compared with patients exhibiting a low expression (P<0.01 and P<0.05, respectively). Subsequent in vitro experiments revealed that cell growth decreased following knockdown of ATF2 expression using RNA interference, indicating that ATF2 may suppress cell proliferation. Taken together, the results of the present study demonstrated that ATF2 and p-ATF2 were significantly overexpressed in NSCLC tissues, and ATF2 and p-ATF2 overexpression predicted significantly worse outcomes for patients with NSCLC.

Ultrasensitive nonlinear absorption response of large-size topological insulator and application in low-threshold bulk pulsed lasers.

Dirac-like topological insulators have attracted strong interest in optoelectronic application because of their unusual and startling properties. Here we report for the first time that the pure topological insulator Bi2Te3 exhibited a naturally ultrasensitive nonlinear absorption response to photoexcitation. The Bi2Te3 sheets with lateral size up to a few micrometers showed extremely low saturation absorption intensities of only 1.1 W/cm(2) at 1.0 and 1.3 µm, respectively. Benefiting from this sensitive response, a Q-switching pulsed laser was achieved in a 1.0 µm Nd:YVO4 laser where the threshold absorbed pump power was only 31 mW. This is the lowest threshold in Q-switched solid-state bulk lasers to the best of our knowledge. A pulse duration of 97 ns was observed with an average power of 26.1 mW. A Q-switched laser at 1.3 µm was also realized with a pulse duration as short as 93 ns. Moreover, the mode locking operation was demonstrated. These results strongly exhibit that Bi2Te3 is a promising optical device for constructing broadband, miniature and integrated high-energy pulsed laser systems with low power consumption. Our work clearly points out a significantly potential avenue for the development of two-dimensional-material-based broadband ultrasensitive photodetector and other optoelectronic devices.

Single-longitudinal-mode Er:GGG microchip laser operating at 2.7 µm.

We reported on a diode-end-pumped single-longitudinal-mode microchip laser using a 600-µm-thick Er:GGG crystal at ∼2.7 µm, generating a maximum output power of 50.8 mW and the maximum pulsed energy of 0.306 mJ, with repetition rates of pumping light of 300, 200, and 100 Hz, respectively. The maximum slope efficiency of the laser was 20.1%. The laser was operated in a single-longitudinal mode centered at about 2704 nm with a FWHM of 0.42 nm. The laser had a fundamental beam profile and the beam quality parameter M(2) was measured as 1.46. These results indicate that the Er:GGG microchip laser is a potential compact mid-infrared laser source.

Dual function of Nd3+ in Nd,Er:LuYSGG crystal for LD pumped ~3.0 µm mid-infrared laser.

Enhanced ~3.0 µm emission corresponding to Er3+:4I11/2→4I13/2 was achieved in Nd3+/Er3+ co-doped Lu0.15Y2.85Sc2Ga3O12 (abbr. as Nd,Er:LuYSGG) crystal under 808 nm pumping. As compared with Er:YSGG crystal, the absorption pump efficiency of Nd,Er:LuYSGG crystal is greatly improved and thus ~3.0 µm emission is enhanced by 2.2 times owing to the sensitization of Nd3+, at the same time, Nd3+ as deactivator quenches ~1.5 µm emission from Er3+:4I13/2 level and thus inhibit the self-termination effect successfully. The energy transfer efficiencies of Nd: 4F3/2→Er: 4I11/2 and Er: 4I13/2→Nd:4I15/2 are estimated to be 91.6% and nearly 100%, respectively. These results indicate that the introduction of Nd3+ is very helpful for achieving ~3.0 µm laser in Nd,Er:LuYSGG crystal.

Analyzing the differentially expressed genes and pathway cross-talk in aggressive breast cancer.

AIM: The aim of this study was to explore the genes and pathways involved in the aggressive breast cancer cells. METHODS: The gene expression profiles of GSE40057, including four aggressive breast cell lines and six less aggressive cell lines, were downloaded from the Gene Expression Omnibus (GEO) database. The gene differential expression analysis was carried out with limma software with the method of Bayes for multiple tests. The gene ontology (GO) term enrichment and pathway cross-talk analysis were performed with the online tool of DAVID and Cytoscape software. RESULTS: A total of 401 differentially expressed genes (DEG), such as pentraxin 3 (PTX3), snail family zinc finger 2 (SNAI2), interleukin-8/6 (IL-8/6), osteonectin (SPARC), matrix metallopeptidase-1 (MMP-1) and Ras-related protein Rab-25 (Rab 25), were identified between aggressive and less aggressive cell lines. They were mainly enriched in the GO terms of response to wounding, negative regulation of cell proliferation and calcium binding. Pathways in cancer dysfunctionally interacted with glyoxylate and dicarboxylate metabolism (P < 0.0001), basal transcription factors (P < 0.0001), tyrosine metabolism (P < 0.0001), calcium signaling pathway (P = 0.0021), FcγR-mediated phagocytosis (P = 0.0022), metabolism of xenobiotics by cytochrome P450 (P = 0.0097) and phagosome (P = 0.0102). CONCLUSION: The screened aggressive cancer-associated DEG (PTX3, SNAI2, IL-8/6, SPARC, MMP-1 and Rab25) and significant pathways (calcium signaling pathway, tyrosine metabolism, alanine, aspartate and glutamate metabolism) give us new insights into the mechanism of aggressive breast cancer cells, and these DEG may become promising target genes in the treatment of metastatic breast cancer.

2.4 W highly efficient simultaneous dual-wavelength laser operation of monoclinic Yb(3+):Ca4LaO(BO3)3 crystals.

We have studied the simultaneous dual-wavelength laser operation of the X-cut, Y-cut, and Z-cut Yb(3+):Ca4LaO(BO3)3 crystals for the first time to the best of our knowledge. We analyzed the dual-wavelength laser output power and emission spectra under several output coupler transmittances. The stable dual-wavelength lasers were generated by adjusting the laser elements. A dual-wavelength laser output power 2.46 W was obtained with a slope efficiency of 67.5% by employing the Y-cut crystal at 1029 and 1036 nm. The two wavelengths had nearly the same relative intensity. The two different emission wavelengths were found to change with crystal direction and output coupler transmittance. This laser has a possible application as the laser source in the generation of different terahertz waves.

The novel role of thymopentin in induction of maturation of bone marrow dendritic cells (BMDCs).

Thymopentin is an immune-modulating peptide that can stimulate cellular immune responses and has been used in many immune handicapped cases [1]. However, despite documented reports proving its efficacy in immunoregulation, there have been no reports, as yet, concerning its impact on the maturation and function of dendritic cells (DCs). In this study, we analyzed the effects of thymopentin on the detailed regulation of maturation of murine bone-marrow-derived DCs (BMDCs). The phenotypic and structural maturation of BMDCs was confirmed by transmission electron microscopy (TEM) and flow cytometry (FCM). The functional maturation was confirmed by an acid phosphatase (ACP) activity test, FITC-dextran bio-assay, test of 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE), labeled CD4(+)T cell proliferation and enzyme-linked immunosorbent assay (ELISA). We determined that thymopentin up-regulated the expression of CD40, CD80, CD86, CD83, and MHC II molecules on BMDCs, down-regulated phagocytosis of BMDCs, increased BMDCs driven CD4(+)T cell proliferation, and enhanced BMDC production of IL-12 and TNF-α. Therefore, we concluded that thymopentin highly induces BMDC maturation and intensifies DC/T-cell pathways. These data also provide direct evidence and rationale concerning the potential clinical use of thymopentin in various immune handicapped cases and suggest that thymopentin should be considered as a potent adjuvant for DC-based vaccines.

Self-Q-switched, orthogonally polarized, dual-wavelength laser using long-lifetime Yb³âº crystal as both gain medium and saturable absorber.

A novel self-Q-switched and orthogonally polarized dual-wavelength laser has been investigated with Yb³âº-doped CGB disordered crystals. By slightly inclining output coupler to introduce the Fresnel loss, we realized simultaneously dual-wavelength laser operation at 1052.6 nm in E//b polarization and 1057.7 nm in E//c polarization with a frequency difference of 1.38 THz. Self-Q-switched pulse generation was observed in this free-running laser, originating from the nonlinear reabsorption effect of Yb:CGB as well as the strong storage of inversion population induced by the long excited-state lifetime (~1 ms). Pulse duration of 287 ns was obtained with an output average power of 416 mW and a repetition rate of 35 kHz. The self-Q-switching effect increased the peak power by 100 times the average power. This very simple laser, free from the complexity and high-cost of additional intracavity polarization modulator and Q-switcher, may be applied for constructing miniature, integrated and portable laser system.