High power, broad tuning quantum cascade laser at λ ∼ 8.9 µm.

Many molecules have broad fingerprint absorption spectra in mid-wave infrared range which requires broadly tunable lasers to cover the interested spectrum in one scan. We report a strain-balanced, InAlAs/InGaAs/InP quantum cascade laser structure based on diagonal transition active region with high output power and and wide tuning range at λ ∼ 8.9 µm. The maximum pulsed optical power and the wall-plug efficiency at room temperature are 4 W and 11.7%, respectively. Maximum continuous wave double-facet power is 1.2 W at 25 °C for a 4 mm by 9 µm laser mounted epi-side down on a diamond/copper composite submount. The maximum pulsed and continuous wave external-cavity tuning range are from 7.71 µm to 9.15 µm and from 8 µm to 8.9 µm, respectively. The continuous wave power of the external cavity mode exceeds 200 mW across the entire spectrum.

Broad tuning range, high power quantum cascade laser at λ ∼ 7.4 µm.

In this article, we report a high power quantum cascade laser (QCL) at λ∼7.4 µm with a broad tuning range. By carefully designing and optimizing the active region and waveguide structure, a continuous-wave (CW) output power up to 1.36 W and 0.5 W is achieved at 293 K and 373 K which shows the excellent temperature stability. A high wall-plug efficiency (WPE) of 8% and 13.6% in CW and pulsed mode at 293 K are demonstrated. The laser shows a characteristic temperature T0 of 224 K and T1 of 381 K over a temperature range from 283 K to 373 K. In addition, a far field of pure zero order transverse mode and a fairly wide external cavity (EC) tuning range (280 cm-1) from 6.54 µm to 8 µm are achieved in pulsed operation. In addition, an EC single mode output power of 226 mW is obtained under CW operation at 293K.

GaSb surface grating distributed feedback interband cascade laser emitting at 3.25 µm.

A second-order distributed feedback interband cascade laser emitting at 3.25 µm was designed, grown, and fabricated. By coherent epitaxy of a GaSb cap layer instead of the conventional thin InAs cap on top of the laser structure, a high-quality surface grating was made of GaSb and gold. Enough coupling strength and a significant inter-modal loss difference were predicted according to the simulation within the framework of couple-wave theory. Lasers having 2-mm-long cavities and 4.5-µm-wide ridges with high-/anti-reflection coatings were fabricated. The continuous-wave threshold current and maximum single-mode output power were 60 mA and 24 mW at 20°C, respectively. The output power of 5 mW was still kept at 55°C. Continuous tuning free from mode hopping and high single-mode suppression ratios (>20 dB) were realized at all injection currents and heat-sink temperatures, covering a spectral range of over 20 cm-1.

HCMV modulates c-Mpl/IEX-1 pathway-mediated megakaryo/thrombopoiesis via PDGFRα and αvß3 receptors after allo-HSCT.

Thrombocytopenia is a common complication of human cytomegalovirus (HCMV) infection in immunocompromised hosts, which contributes to poor prognosis even in patients receiving antiviral treatment. Here, we investigated the megakaryo/thrombopoiesis process, including the involvement of the c-Mpl/IEX-1 pathway, after HCMV infection, identified receptors mediating the interaction between megakaryocytes (MKs) and HCMV, and explored novel therapeutic targets. Our data shows that HCMV directly infects megakaryocytes in patients with HCMV DNAemia and influences megakaryopoiesis via the c-Mpl/IEX-1 pathway throughout megakaryocyte maturation, apoptosis, and platelet generation in vivo and in vitro. After treatment with inhibitors of PDGFRα and αvß3, the HCMV infection rate in MKs was significantly reduced, suggesting that IMC-3G3 and anti-αvß3 are potential therapeutic alternatives for viral infection. In summary, our study proposes a possible mechanism and potential treatments for thrombocytopenia caused by HCMV infection and other viral diseases associated with abnormal hemostasis.

Prediction of postpartum hemorrhage in pregnant women with immune thrombocytopenia: Development and validation of the MONITOR model in a nationwide multicenter study.

Globally, postpartum hemorrhage (PPH) is the leading cause of maternal death. Women with immune thrombocytopenia (ITP) are at increased risk of developing PPH. Early identification of PPH helps to prevent adverse outcomes, but is underused because clinicians do not have a tool to predict PPH for women with ITP. We therefore conducted a nationwide multicenter retrospective study to develop and validate a prediction model of PPH in patients with ITP. We included 432 pregnant women (677 pregnancies) with primary ITP from 18 academic tertiary centers in China from January 2008 to August 2018. A total of 157 (23.2%) pregnancies experienced PPH. The derivation cohort included 450 pregnancies. For the validation cohort, we included 117 pregnancies in the temporal validation cohort and 110 pregnancies in the geographical validation cohort. We assessed 25 clinical parameters as candidate predictors and used multivariable logistic regression to develop our prediction model. The final model included seven variables and was named MONITOR (maternal complication, WHO bleeding score, antepartum platelet transfusion, placental abnormalities, platelet count, previous uterine surgery, and primiparity). We established an easy-to-use risk heatmap and risk score of PPH based on the seven risk factors. We externally validated this model using both a temporal validation cohort and a geographical validation cohort. The MONITOR model had an AUC of 0.868 (95% CI 0.828-0.909) in internal validation, 0.869 (95% CI 0.802-0.937) in the temporal validation, and 0.811 (95% CI 0.713-0.908) in the geographical validation. Calibration plots demonstrated good agreement between MONITOR-predicted probability and actual observation in both internal validation and external validation. Therefore, we developed and validated a very accurate prediction model for PPH. We hope that the model will contribute to more precise clinical care, decreased adverse outcomes, and better health care resource allocation.

Analysis of differentially expressed genes in rheumatoid arthritis and osteoarthritis by integrated microarray analysis.

BACKGROUND: Rheumatoid arthritis (RA) and osteoarthritis (OA) were two major types of joint diseases. This study aimed to explore the mechanism underlying OA and RA and analyze their difference by integrated analysis of multiple gene expression data sets. METHODS: Gene expression data sets of RA and OA were downloaded from The Gene Expression Omnibus. Shared and specific differentially expressed genes (DEGs) in RA and OA were identified by integrated analysis of multiple gene expression data sets. Functional annotation and protein-protein interaction (PPI) network construction of OA- and RA-specific DEGs were performed to further explore the molecular mechanisms underlying RA and OA and analyze the mechanism differences between them. RESULTS: Compared with normal controls, 3757 and 2598 DEGs were identified in RA and OA, respectively. Among them, 2176 DEGs were RA-specific DEGs and 1017 DEGs were OA-specific DEGs. Moreover, the expression of 17 DEGs played opposite pattern in RA and OA compared with normal controls. Chemokine signaling pathway and oxidative phosphorylation were significantly enriched pathways for RA- and OA-specific DEGs, respectively. BIRC2 and CSNK1E were respective hub genes of RA- and OA-specific PPI network. CONCLUSION: Our findings provided clues for the specific mechanism and developing specific biomarkers for RA and OA.

Surgical therapy vs conservative therapy for patients with acute injury of lateral ankle ligament: A meta-analysis and systematic review.

The goal of this meta-analysis was to explore the overall safety and efficacy of surgical therapy vs conservative therapy for acute injury of the lateral ankle ligament based on eligible studies. Eligible studies were identified by searching PubMed, Cochrane, and Embase databases using appropriate updated index words to January 2018. We also searched relevant publication sources. Eligible studies included randomised controlled trials and comparative studies. Mean difference or relative risk (RR), along with 95% confidence interval (CI), was used to analyse the main outcomes. A total of 13 studies were eligible for this meta-analysis, with 834 patients in the surgical therapy group and 930 patients in the conservative therapy group. Compared with patients receiving conservative treatment, patients undergoing surgical treatment had a significant higher American Orthopedic Foot And Ankle Society (AOFAS) score (weighted mean difference(WMD): 10.33, 95% CI: 6.83-13.83) and an effective rate (RR: 1.15, 95% CI: 1.04-1.28). No significant differences were observed in the incidence of recurrent ankle injury (RR: 1.01, 95% CI: 0.62-1.65), limited range of motion (RR: 1.44, 95% CI: 0.83-2.50), deep vein thrombosis (RR: 1.33, 95% CI: 0.73-2.41), and wound infection or necrosis (RR: 3.99, 95% CI: 0.45-35.34). However, compared with patients receiving conservative treatment, patients undergoing surgical therapy had significantly increased rates of complications (RR: 3.31, 95% CI: 2.55-4.28), ankylosis (RR: 3.63, 95% CI: 2.16-6.08), scare tenderness (RR: 10.16, 95% CI: 3.89-26.52) and sensory loss (RR: 5.66, 95% CI: 2.76-11.59). The results demonstrated that surgical treatment increased the AOFAS score and effective rate compared with conservative treatment. Besides, surgical treatment increased the rate of complications. Nevertheless, more high-quality randomised controlled trials with a larger sample size conducted at multiple centres with a long-term follow up are needed to confirm our conclusions.

Low voltage-defect quantum cascade lasers based on excited-states injection at λ ∼ 8.5 µm.

A quantum cascade laser emitting at λ∼8.5 µm based on the excited-state injection is presented. The operating voltage is reduced for a low-voltage defect in the excited-state design, compared with the conventional ground-state injection design. The threshold voltage and voltage defect are as low as 6.3 V and 54 mV for a 30-stage active region, respectively. Devices were fabricated through standard buried-heterostructure processing to decrease the heat accumulation. A continuous-wave optical power of 340 mW is obtained at 283 K with a threshold current density of 2.7 kA/cm2. Such a design has the potential to further improve the wall plug efficiency for increased voltage efficiency.

Room temperature continuous wave quantum dot cascade laser emitting at 7.2 µm.

We demonstrate a quantum cascade laser with active regions consisting of InAs quantum dots deposited on GaAs buffer layers that are embedded in InGaAs wells confined by InAlAs barriers. Continuous wave room temperature lasing at the wavelength of 7.2 µm has been demonstrated with the threshold current density as low as 1.89 kA/cm2, while in pulsed operational mode lasing at temperatures as high as 110 °C had been observed. A phenomenological theory explaining the improved performance due to weak localization of states had been formulated.

High efficiency, single-lobe surface-emitting DFB/DBR quantum cascade lasers.

We demonstrate a surface-emitting quantum cascade laser (QCL) based on second-order buried distributed feedback/distributed Bragg reflector (DFB/DBR) gratings for feedback and outcoupling. The grating fabricated beneath the waveguide was found to fundamentally favor lasing in symmetric mode either through analysis or experiment. Single-lobe far-field radiation pattern with full width at half maximum (FWHM) of 0.18° was obtained along the cavity-length direction. Besides, the buried DFB/DBR grating structure successfully provided an efficient vertical outcoupling mechanism with low optical losses, which manages to achieve a high surface outcouping efficiency of 46% in continuous-wave (CW) operation and 60% in pulsed operation at room temperature. Single-mode emission with a side-mode suppression ratio (SMSR) about 25 dB was continuously tunable by heat sink temperature or injection current. Our work contributes to the realization of high efficiency surface-emitting devices with high far-field beam quality that are significantly needed in many application fields.

Small divergence substrate emitting quantum cascade laser by subwavelength metallic grating.

Metallic periodic structure in subwavelength scale offers an exciting way to couple light into surface plasmons (SPs), thus manipulating the properties of near-field optics. We show that subwavelength metallic grating (SMG) defined on the substrate side of substrate emitting quantum cascade lasers enables far-field improvement in mid-infrared spectrum. The SMG is designed to tailor the interaction of SPs with single mode transverse magnetic light. The experiment results are in good agreement with the simulated model. A far-field full width at half maximum (FWHM) divergence angle of 3.9 ° in the direction perpendicular to the laser waveguide layers is obtained, improved by a factor of 8.5 compared with traditional surface emitting device.

Antioxidation and anti-inflammatory activity of Tang Bi Kang in rats with diabetic peripheral neuropathy.

BACKGROUND: Tang Bi Kang (TBK) is a traditional Chinese medicine granule. It has been shown to have effects on nerve conduction velocity deficits, blood-related factors and oxidative stress. This study was undertaken to evaluate proposed antioxidative and anti-inflammatory activity of Tang Bi Kang in rats with diabetic peripheral neuropathy (DPN). METHODS: DPN was induced in male Wistar rats by intraperitoneal administration of streptozocin (STZ) (60 mg/kg.b.w) for 8 weeks. Fasting blood glucose (FBG) levels were measured in the blood obtained by clipping the tails of the rats. Tail-flick tests were conducted with a tail-flick analgesic meter. Motor and sensory nerve conduction velocities (MNCV and SNCV) of sciatic nerve were measured directly at two sites using a Functional Experiment System. Oxidative stress makers such as malondialdehyde (MDA), superoxide-dismutase (SOD) and glutathione peroxidase (GSH-Px), inflammatory cytokines such as interleukin (IL)-6, and tumour necrosis factor (TNF)-α were estimated. The statistical analysis of results was carried out using Student t-test and one-way analysis of variance (ANOVA), followed by least-significant difference post hoc with SPSS. RESULTS: The administration of TBK for 4 weeks in DPN rats resulted in a significant decrease in FBG levels compared to untreated DPN rats. There was a significant increase in MNCV and SNCV in the DPN rats compared to untreated DPN rats. Serum level of MDA was significantly reduced while the activities of SOD and GSH-pX were significantly increased in the TBK treated DPN rats. TBK prevented DPN-induced increase in the serum levels of IL-6 and TNF-α. CONCLUSION: The results of this study demonstrate that the therapeutic effect of TBK on DPN rats may be associated with the antioxidative and anti-inflammatory responses.

Tri-channel single-mode terahertz quantum cascade laser.

We report on a compact THz quantum cascade laser source emitting at, individually controllable, three different wavelengths (92.6, 93.9, and 95.1 µm). This multiwavelength laser array can be used as a prototype of the emission source of THz wavelength division multiplex (WDM) wireless communication system. The source consists of three tapered single-mode distributed feedback (DFB) terahertz quantum cascade lasers fabricated monolithically on a single chip. All array elements feature longitudinal as well as lateral single-mode in the entire injection range. The peak output powers of individual lasers are 42, 73, and 37 mW at 10 K, respectively.

The effects of high thoracic epidural anesthesia on sympathetic activity and apoptosis in experimentally induced congestive heart failure.

OBJECTIVE: To evaluate the effect of high thoracic epidural analgesia (HTEA) in congestive heart failure (CHF). DESIGN: Rat model of CHF. SETTING: Harbin Medical University, Harbin, Heilongjiang, China. PARTICIPANTS: One hundred thirty-five rats. INTERVENTIONS: HTEA involved 5 times daily injections of 0.1% lidocaine at the T3-T4 level. MEASUREMENTS AND MAIN RESULTS: The authors examined myocardial norepinephrine (NE), angiotensin II (Ang II), endothelin-1 (ET1), and tumor necrosis factor-α (TNF-α) concentrations 2, 4, and 6 weeks after the start of HTEA. They also examined histologic changes in heart tissue and myocardial expression of apoptosis-inducing factor (AIF) and poly (ADP-ribose) polymerase (PARP). Sham rats were used as a control. In the time course, myocardial NE, Ang II, ET1, and TNF-α concentrations were significantly higher in the CHF group compared with the HTEA and sham groups (p< 0.05). Similarly, PARP and AIF protein expression levels were significantly higher in the CHF group compared with the HTEA and sham groups (p< 0.05). Microscopy revealed pronounced damage to myocardial cell structures in the CHF group; this damage clearly was reduced in the HTEA group. In addition, cardiac function evaluation indicated treatment with HTEA resulted in similar heart function as animals that did not have surgically induced CHF. CONCLUSIONS: The findings suggest that HTEA induces changes in sympathetic nervous system, renin-angiotensin system, endothelial, and inflammatory process activity involved in CHF.

High dimensional proteomic mapping of bone marrow immune characteristics in immune thrombocytopenia.

To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia (ITP), this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight (CyTOF). Thirty-six patients with ITP and nine healthy volunteers were enrolled in the study. As soluble immunomodulatory molecules, more sCD25 and sGalectin-9 were detected in ITP patients. On the cell surface, co-stimulatory molecules like ICOS and HVEM were observed to be upregulated in mainly central memory and effector T cells. In contrast, co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th17 cell subsets. Taking a platelet count of 30×109 L-1 as the cutoff value, ITP patients with high and low platelet counts showed different T cell immune profiles. Antigen-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions, respectively, and participate in the pathogenesis of ITP. In conclusion, the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of ITP. They may offer novel targets to develop personalized immunotherapies.

Fabrication of magnetic-antimicrobial-fluorescent multifunctional hybrid microspheres and their properties.

Novel magnetic-antimicrobial-fluorescent multifunctional hybrid microspheres with well-defined nanostructure were synthesized by the aid of a poly(glycidyl methacrylate) (PGMA) template. The hybrid microspheres were fully characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), X-ray diffraction (XRD) and digital fluorescence microscope. The as-synthesized microspheres PGMA, amino-modified PGMA (NH2-PGMA) and magnetic PGMA (M-PGMA) have a spherical shape with a smooth surface and fine monodispersity. M-PGMA microspheres are super-paramagnetic, and their saturated magnetic field is 4.608 emu·g-1, which made M-PGMA efficiently separable from aqueous solution by an external magnetic field. After poly(haxemethylene guanidine hydrochloride) (PHGH) functionalization, the resultant microspheres exhibit excellent antibacterial performance against both Gram-positive and Gram-negative bacteria. The fluorescence feature originating from the quantum dot CdTe endowed the hybrid microspheres with biological functions, such as targeted localization and biological monitoring functions. Combination of magnetism, antibiosis and fluorescence into one single hybrid microsphere opens up the possibility of the extensive study of multifunctional materials and widens the potential applications.

ß2-adrenergic receptor agonist corrects immune thrombocytopenia by reestablishing the homeostasis of T cell differentiation.

BACKGROUND: The sympathetic nerve is known to regulate immune responses in autoimmunity. Aberrant T cell immunity plays a vital role in immune thrombocytopenia (ITP) pathogenesis. The spleen is the primary site of platelet destruction. However, little is known whether and how splenic sympathetic innervation and neuroimmune modulation contribute to ITP pathogenesis. OBJECTIVES: To determine the sympathetic distribution in the spleen of ITP mice and the association between splenic sympathetic nerves and T cell immunity in ITP development, and to evaluate the treatment potential of ß2-adrenergic receptor (ß2-AR) in ITP. METHODS: Chemical sympathectomy was performed in an ITP mouse model with 6-hydroxydopamine and treated with ß2-AR agonists to evaluate the effects of sympathetic denervation and activation. RESULTS: Decreased sympathetic innervation in the spleen of ITP mice was observed. Significantly increased percentages of Th1 and Tc1 cells and reduced percentages of regulatory T cells (Tregs) were also observed in ITP mice with chemical sympathectomy (ITP-syx mice) relative to mice without sympathectomy (controls). Expression of genes associated with Th1, including IFN-γ and IRF8, was significantly upregulated, whereas genes associated with Tregs, including Foxp3 and CTLA4, were significantly downregulated in ITP-syx mice compared with controls. Furthermore, ß2-AR restored the percentage of Tregs and increased platelet counts at days 7 and 14 in ITP mice. CONCLUSION: Our findings indicate that decreased sympathetic distribution contributes to ITP pathogenesis by disturbing the homeostasis of T cells and that ß2-AR agonists have potential as a novel treatment for ITP.

[Mid-infrared distributed-feedback quantum cascade laser-based photoacoustic detection of trace methane gas].

There have been considerable interests in methane detection based on infrared absorption spectroscopy for industrial and environment monitoring. The authors report on the realization of photoacoustic detection of methane (CH4) using mid-infrared distributed-feedback quantum cascade laser (DFB-QCL). The absorption line at 1316.83 cm(-1) was selected for CH4 detection, which can be reached by the self-manufactured DFB-QCL source operating in pulsed mode near 7.6 microm at room-temperature. The CH4 gas is filled to a Helmholtz resonant photoacoustic cell, which was equipped with a commercial electret microphone. The DFB-QCL was operated at 234 Hz with an 80 mW optical peak power. A detection limit of 189 parts per billion in volume was derived when the signal-to-noise ratio equaled 1.

Cerebrospinal Fluid sTREM2 in Alzheimer's Disease Is Associated with Both Amyloid and Tau Pathologies but not with Cognitive Status.

BACKGROUND: Cerebrospinal fluid (CSF) soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is considered a biomarker of microglial activation. The relationships between CSF sTREM2 levels and Alzheimer's disease (AD) CSF core biomarkers, cognitive status, and neurodegeneration remain unclear. OBJECTIVE: To assess the association between CSF sTREM2 levels and AD progression and other AD hallmarks. METHODS: Using the Alzheimer's Disease Neuroimaging Initiative database, we investigated 1,035 participants, including 310 cognitively normal controls, 527 patients with mild cognitive impairment, and 198 patients with dementia. They were grouped according to CSF pathology (A/T profile) severity. CSF sTREM2 levels were compared between the groups, and linear regression analysis was performed to evaluate the factors affecting sTREM2 levels. The predictive effectiveness of sTREM2 levels was tested, and the correlation with other indicators was explored. The increase rate was assessed using linear mixed-effects models. RESULTS: Higher CSF sTREM2 levels were associated with older age as well as higher CSF p-tau or t-tau and amyloid-ß levels (all p < 0.001), but not with cognitive status. sTREM2 levels were not correlated with the baseline or longitudinal scale and neuroimaging result changes, and could not predict clinical conversion, but were correlated with multiple non-amyloid-ß and non-tau CSF cytokines related to inflammation and neurodegeneration (p < 0.0001). The increased sTREM2 expression rate did not change among groups. CONCLUSION: CSF sTREM2 levels were jointly determined by age, amyloid-ß, and tau pathologies, leading to complex AD cognitive continuum changes. Although sTREM2 levels could not predict cognitive deterioration and neurodegeneration, they could reflect the microglial state as a non-specific biomarker.

ß-Amyloid promotes platelet activation and activated platelets act as bridge between risk factors and Alzheimer's disease.

Alzheimer's disease (AD) is an evolving challenge that places an enormous burden on families and society. The presence of obvious brain ß-amyloid (Aß) deposition is a premise to diagnose AD, which induces the subsequent tau hyperphosphorylation and neurodegeneration. Platelets are the primary source of circulating amyloid precursor protein (APP). Upon activation, they can secrete significant amounts of Aß into the blood, which can be actively transported to the brain across the blood-brain barrier and promote amyloid deposition. In this review, we summarized the changes in the platelet APP metabolic pathway in patients with AD and further comprehensively explored the targets and downstream events of Aß-activated platelets. In addition, we attempted to clarify whether patients with AD are in a state of general platelet activation, with inconsistent results. Considering the increasingly evident bidirectional relationship between AD and vascular events, we speculate that the AD pathology alone seems to be insufficient to induce the general activation of platelets; however, the intervention of third-party factors, such as atherosclerosis, exposes the extracellular matrix and leads to platelet activation, further promoting AD progression. Therefore, we proposed a framework in which the relationship between platelets and AD is indirect and mediated by vascular factors. Therapies targeting platelets and interventions for vascular risk factors are likely to contribute to the prevention and treatment of AD.