In-band pumped Kerr-lens mode-locked Tm,Ho-codoped calcium aluminate laser.

We report on a Kerr-lens mode-locked Tm,Ho-codoped calcium aluminate laser with in-band pumping of the Tm ions by a spatially single-mode 1678 nm Raman fiber laser. The structurally disordered CaGdAlO4 host crystal is also codoped also with the passive Lu ion for additional inhomogeneous line broadening. The Tm,Ho,Lu:CaGdAlO4 laser generates soliton pulses as short as 79 fs at a central wavelength of 2073.6 nm via soft-aperture Kerr-lens mode-locking. The corresponding average output power amounts to 91 mW at a pulse repetition rate of ∼86 MHz. The average output power can be scaled to 842 mW at the expense of slightly longer pulses of 155 fs at 2045.9 nm, which corresponds to a peak power of ∼58 kW. To the best of our knowledge, this represents the first demonstration of an in-band pumped Kerr-lens mode-locked Tm,Ho solid-state laser at ∼2 µm.

Extracellular vesicles from UTX-knockout endothelial cells boost neural stem cell differentiation in spinal cord injury.

BACKGROUND: Vascular endothelial cells are pivotal in the pathophysiological progression following spinal cord injury (SCI). The UTX (Ubiquitously Transcribed Tetratripeptide Repeat on Chromosome X) serves as a significant regulator of endothelial cell phenotype. The manipulation of endogenous neural stem cells (NSCs) offers a compelling strategy for the amelioration of SCI. METHODS: Two mouse models were used to investigate SCI: NSCs lineage-traced mice and mice with conditional UTX knockout (UTX KO) in endothelial cells. To study the effects of UTX KO on neural differentiation, we harvested extracellular vesicles (EVs) from both UTX KO spinal cord microvascular endothelial cells (SCMECs) and negative control SCMECs. These EVs were then employed to modulate the differentiation trajectory of endogenous NSCs in the SCI model. RESULTS: In our NSCs lineage-traced mice model of SCI, a marked decrease in neurogenesis was observed post-injury. Notably, NSCs in UTX KO SCMECs mice showed enhanced neuronal differentiation compared to controls. RNA sequencing and western blot analyses revealed an upregulation of L1 cell adhesion molecule (L1CAM), a gene associated with neurogenesis, in UTX KO SCMECs and their secreted EVs. This aligns with the observed promotion of neurogenesis in UTX KO conditions. In vivo administration of L1CAM-rich EVs from UTX KO SCMECs (KO EVs) to the mice significantly enhanced neural differentiation. Similarly, in vitro exposure of NSCs to KO EVs resulted in increased activation of the Akt signaling pathway, further promoting neural differentiation. Conversely, inhibiting Akt phosphorylation or knocking down L1CAM negated the beneficial effects of KO EVs on NSC neuronal differentiation. CONCLUSIONS: In conclusion, our findings substantiate that EVs derived from UTX KO SCMECs can act as facilitators of neural differentiation following SCI. This study not only elucidates a novel mechanism but also opens new horizons for therapeutic interventions in the treatment of SCI. Video Abstract.

Inhibition of UTX/KDM6A improves recovery of spinal cord injury by attenuating BSCB permeability and macrophage infiltration through the MLCK/p-MLC pathway.

Spinal cord injury (SCI) can prompt an immediate disruption to the blood-spinal cord barrier (BSCB). Restoring the integrity of this barrier is vital for the recovery of neurological function post-SCI. The UTX protein, a histone demethylase, has been shown in previous research to promote vascular regeneration and neurological recovery in mice with SCI. However, it is unclear whether UTX knockout could facilitate the recovery of the BSCB by reducing its permeability. In this study, we systematically studied BSCB disruption and permeability at different time points after SCI and found that conditional UTX deletion in endothelial cells (ECs) can reduce BSCB permeability, decrease inflammatory cell infiltration and ROS production, and improve neurological function recovery after SCI. Subsequently, we used RNA sequencing and ChIP-qPCR to confirm that conditional UTX knockout in ECs can down-regulate expression of myosin light chain kinase (MLCK), which specifically mediates myosin light chain (MLC) phosphorylation and is involved in actin contraction, cell retraction, and tight junctions (TJs) protein integrity. Moreover, we found that MLCK overexpression can increase the ratio of p-MLC/MLC, further break TJs, and exacerbate BSCB deterioration. Overall, our findings indicate that UTX knockout could inhibit the MLCK/p-MLC pathway, resulting in decreased BSCB permeability, and ultimately promoting neurological recovery in mice. These results suggest that UTX is a promising new target for treating SCI.

Endothelial progenitor cell-derived exosomes promote anti-inflammatory macrophages via SOCS3/JAK2/STAT3 axis and improve the outcome of spinal cord injury.

BACKGROUND: Macrophage in the spinal cord injury (SCI) area imparts a chronic pro-inflammation effect that challenges the recovery of SCI. Previously, endothelial progenitor cell-produced exosomes (EPC-EXOs) have been noticed to facilitate revascularization and inflammation control after SCI. However, their effects on macrophage polarization remained unclear. This study aimed to investigate the EPC-EXOs' role in macrophage polarization and reveal its underlying mechanism. METHODS: We extracted the macrophages and EPC from the bone marrow suspension of C57BL/L mice by centrifugation. After cell identification, the EPC-EXOs were collected by ultra-high-speed centrifugation and exosome extraction kits and identified by transmission electron microscopy and nanoparticle tracking analysis. Then, macrophages were cultured with EPC-EXOs in different concentrations. We labeled the exosome to confirm its internalization by macrophage and detected the macrophage polarization marker level both in vitro and in vivo. We further estimated EPC-EXOs' protective effects on SCI by mice spinal cord tissue H&E staining and motor behavior evaluation. Finally, we performed RT-qPCR to identify the upregulated miRNA in EPC-EXOs and manipulate its expression to estimate its role in macrophage polarization, SOCS3/JAK2/STAT3 pathway activation, and motor behavior improvement. RESULTS: We found that EPC-EXOs decreased the macrophages' pro-inflammatory marker expression and increased their anti-inflammatory marker expression on the 7 and 14 days after SCI. The spinal cord H&E staining results showed that EPC-EXOs raised the tissue-sparing area rate significantly after 28 days of SCI and the motor behavior evaluation indicated an increased BMS score and motor-evoked potential by EPC-EXOs treatment after SCI. The RT-qPCR assay identified that miR-222-3P upregulated in EPC-EXOs and its miRNA-mimic also decreased the pro-inflammatory macrophages and increased the anti-inflammatory macrophages. Additionally, miR-222-3P mimic activated the SOCS3/JAK2/STAT3 pathway, and SOCS3/JAK2/STAT3 pathway inhibition blocked miR-2223P's effects on macrophage polarization and mouse motor behavior. CONCLUSION: Comprehensively, we discovered that EPC-EXOs-derived miR-222-3p affected macrophage polarization via SOCS3/JAK2/STAT3 pathway and promoted mouse functional repair after SCI, which reveals EPC-EXOs' role in modulation of macrophage phenotype and will provide a novel interventional strategy to induce post-SCI recovery.

MiR-497-3p induces Premature ovarian failure by targeting KLF4 to inactivate Klotho/PI3K/AKT/mTOR signaling pathway.

BACKGROUND: Premature ovarian failure (POF), as a gynecological endocrine disease, features the manifestation of irregular menstruation, amenorrhea, infertility and perimenopausal syndrome. MicroRNAs (miRNAs) have been reported to modulate POF. However, the specific regulatory mechanism of miR-497-3p in POF remain unclear. METHODS: Quantitative reverse transcription-PCR (RT-qPCR) and western blot were implemented to analyze RNA and protein levels, respectively. Comet assay was performed for the detection of DNA damage. Flow cytometry analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were performed to measure apoptosis of CTX-induced KGN cell (POF cell model). Bioinformatics was utilized to screen out the downstream mRNAs potentially regulated by miR-497-3p. Chromatin immunoprecipitation (ChIP) assay, luciferase reporter assay and RNA pulldown assays were performed to demonstrate the interaction between miR-497-3p and Kruppel-like factor 4 (KLF4) or between KLF4 and Klotho (KL). Rescue assays were performed to verify the involvement of Klotho in miR-497-3p-mediated functions of POF cell model. RESULTS: MiR-497-3p was upregulated in CTX-treated KGN cells. Knockdown of miR-497-3p could reverse the promoting effects of CTX on DNA damage and cell apoptosis. MiR-497-3p negatively regulated Klotho expression by directly targeting the transcription activator KLF4. KLF4 activated Klotho transcription. MiR-497-3p inactivated PI3K/AKT/mTOR signaling pathway through KLF4/Klotho axis. Klotho knockdown reversed the effects of MiR-497-3p on the functions of POF cell model. CONCLUSION: MiR-497-3p promotes DNA damage and apoptosis in CTX-treated KGN cells by targeting KLF4 to downregulate Klotho and inactivate the PI3K/AKT/mTOR signaling pathway. This study unveils novel mechanisms associated with cell functional changes in POF and may enrich therapeutic strategy for POF.

The Mature COC Promotes the Ampullary NPPC Required for Sperm Release from Porcine Oviduct Cells.

Porcine spermatozoa are stored in the oviductal isthmus after natural mating, and the number of spermatozoa is increased in the oviductal ampulla when the mature cumulus-oocyte complexes (COCs) are transferred into the ampulla. However, the mechanism is unclear. Herein, natriuretic peptide type C (NPPC) was mainly expressed in porcine ampullary epithelial cells, whereas its cognate receptor natriuretic peptide receptor 2 (NPR2) was located on the neck and the midpiece of porcine spermatozoa. NPPC increased sperm motility and intracellular Ca2+ levels, and induced sperm release from oviduct isthmic cell aggregates. These actions of NPPC were blocked by the cyclic guanosine monophosphate (cGMP)-sensitive cyclic nucleotide-gated (CNG) channel inhibitor l-cis-Diltiazem. Moreover, porcine COCs acquired the ability to promote NPPC expression in the ampullary epithelial cells when the immature COCs were induced to maturation by epidermal growth factor (EGF). Simultaneously, transforming growth factor-ß ligand 1 (TGFB1) levels were dramatically increased in the cumulus cells of the mature COCs. The addition of TGFB1 promoted NPPC expression in the ampullary epithelial cells, and the mature COC-induced NPPC was blocked by the transforming growth factor-ß type 1 receptor (TGFBR1) inhibitor SD208. Taken together, the mature COCs promote NPPC expression in the ampullae via TGF-ß signaling, and NPPC is required for the release of porcine spermatozoa from the oviduct isthmic cells.

Oocyte-secreted factor TGFB2 enables mouse cumulus cell expansion in vitro.

Cumulus expansion is necessary for the release of a fertilizable oocyte from the ovary, which is critical for the normal fertilization of mammals. Cumulus expansion requires cooperation between epidermal growth factor (EGF)-like growth factors and oocyte paracrine factors. Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are well-known paracrine factors secreted by oocytes. In addition, transforming growth factor-ß2 (TGFB2) was primarily expressed in oocytes and its membrane receptors type 1 receptor (TGFBR1) and type 2 receptor (TGFBR2) were located in cumulus cells. In our present study, TGFB2 induced expansion of oocytectomized (OOX) complexes and increased the expression of expansion-related genes in the presence of EGF, suggesting that TGFB2 enables cumulus expansion. Inhibition of TGF-ß signaling with SD208 blocked TGFB2-promoted cumulus expansion. Furthermore, in the culture of OOX complexes from mice of Tgfbr2-specific depletion in granulosa cells, TGFB2-promoted cumulus expansion and the expression of expansion-related genes were impaired. These results suggest that TGFB2 could induce cumulus expansion through TGFBR-SMAD2/3 signaling. Tgfb2-specific depletion in oocytes using Zp3-Cre mice had no effect on cumulus expansion in vivo, possibly due to the compensatory effect of other cumulus expansion-enabling factors. Taken together, TGFB2 is involved in expansion-related gene expression and consequent cumulus expansion.

Struvite-type AMgPO4·6H2O (A = NH4, K): Two Natural Deep-Ultraviolet Transparent Nonlinear Optical Crystals.

Deep-ultraviolet (DUV) nonlinear optical (NLO) materials play vital roles in diverse fields. Unfortunately, only the KBe2BO3F2 crystal has found commercial applications so far. Therefore, the discovery of new DUV NLO crystals is still urgent. As we all know, digging into the properties of existing crystals is also an effective way to obtain new NLO crystals. Herein, two natural asymmetric orthophosphates AMgPO4·6H2O (A = NH4, K) are proposed. Although their structures and some properties such as infrared spectra, thermal properties, and dielectric properties have been previously characterized, their NLO properties have not been reported. Thus, in this work, these two natural DUV transparent orthophosphates NH4MgPO4·6H2O (NMP) and KMgPO4·6H2O (KMP) were successfully acquired by a simple slow evaporation method. The single-crystal X-ray diffraction data indicate that NMP and KMP are isomorphic and that both belong to the Pmn21 space group of the orthorhombic system. Remarkably, NMP and KMP possess short cutoff edges below 190 nm, and their second-harmonic generation (SHG) efficiencies are 0.62 and 0.80 times that of KH2PO4(KDP), respectively; furthermore, they can achieve type-I phase matching at 1064 nm.

Partial nephrectomy provides equivalent oncologic outcomes and better renal function preservation than radical nephrectomy for pathological T3a renal cell carcinoma: A meta-analysis.

PURPOSE: Radical nephrectomy (RN) is the standard surgical type for pathological stage T3a (pT3a) renal cell carcinoma (RCC). Recently, some studies have suggested equivalence between partial nephrectomy (PN) and RN for oncologic control and have shown the benefits of PN for better renal function. We conducted this meta-analysis to assess oncologic outcomes, perioperative outcomes and renal function between two groups among patients with pT3a RCC. MATERIALS AND METHODS: PubMed, Scopus, Web of Science, Science Direct, Ovid MEDLINE, The Cochrane Library, Embase and Google Scholar were searched for eligible articles. The endpoints of the final analysis included overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), surgical complications, operative time, estimated blood loss (EBL), serum creatinine and estimated glomerular filtration rate (eGFR). RESULTS: Twelve studies of moderate to high quality, including 14.152 patients, were examined. PN showed superiority for renal functional preservation, providing higher eGFR (WMD=12.48mL/min; 95%CI: 10.28 to 14.67; P < 0.00001) and lower serum creatinine (WMD=-0.31mg/dL; 95%CI: -0.40 to -0.21; P < 0.00001). There were no significant differences between PN and RN regarding operative time, EBL, surgical complications, OS, RFS and CSS. Despite inherent selection bias, most pooled estimates were consistent in sensitivity analysis and subgroup analysis. More positive margins were found in the PN group (RR=2.42; 95%CI: 1.25-4.68; P=0.009). CONCLUSIONS: PN may be more suitable for treating pT3a RCC than RN because it provides a similar survival time (OS or RFS) and superior renal function. Nevertheless, this result is still disputed, and more high-quality studies are required.

Urinary Tumor Necrosis Factor-Like Weak Inducer of Apoptosis as a Biomarker for Diagnosis and Evaluating Activity in Lupus Nephritis: A Meta-analysis.

OBJECTIVE: Urinary tumor necrosis factor-like weak inducer of apoptosis (uTWEAK) has been identified as a candidate biomarker for lupus nephritis (LN). However, its diagnostic value remains unclear. This meta-analysis was conducted to comprehensively evaluate the value of uTWEAK for diagnosis and evaluating activity in LN. METHODS: Medline, Web of Science, Chinese Biomedical Medical, and Chinese National Knowledge Infrastructure databases were searched to acquire eligible studies published before September 30, 2019. The quality of the studies was evaluated by Quality Assessment of Diagnostic Accuracy Studies-2. Summary receiver operating characteristic curve and area under the curve were applied to summarize the overall diagnostic performances. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated with the fixed-effects model. RevMan 5.3, Stata 12.0, and Meta-disc 1.4 software were used. RESULTS: A total of 7 studies were included. Of these, 4 studies were available for comparison between SLE with and without LN, and 3 studies were for active and inactive LN. The total area under the curve was 0.8640, and DOR was 14.89 (95% confidence interval [CI], 7.95-27.86). For LN diagnosis, the pooled sensitivity, specificity, and DOR were 0.55 (95% CI, 0.47-0.63), 0.92 (95% CI, 0.86-0.96), and 16.54 (95% CI, 7.57-36.15), respectively. For assessing LN activity, the pooled sensitivity, specificity, and DOR were 0.91 (95% CI, 0.82-0.96), 0.70 (95% CI, 0.58-0.81), and 18.45 (95% CI, 7.45-45.87), respectively. CONCLUSIONS: This meta-analysis indicated that uTWEAK has relatively moderate sensitivity and specificity for diagnosis and evaluating activity in LN, suggesting that uTWEAK can serve as a helpful biomarker for LN.

IC261 suppresses progression of hepatocellular carcinoma in a casein kinase 1 δ/ε independent manner.

Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide that responds poorly to existing therapies. The Casein kinase 1 (CK1) isoforms CK1δ and CK1ε are reported to be highly expressed in several tumor types, and both genetic and pharmacological inhibition of CK1δ/ε activity has deleterious effects on tumor cell growth. IC261, an CK1δ/ε selectively inhibitor, shows anti-tumor effect against pancreatic tumor and glioblastoma, but its role in HCC remains poorly characterized. In our research, IC261 displayed time- and dose-dependent inhibition of HCC cell proliferation, and induced G2/M arrest and cell apoptosis in vitro. However, the anti-tumor effects of IC261 was independent of CK1δ/ε. Additionally, IC261 was verified to induce centrosome fragmentation during mitosis independent of CK1δ status, and intraperitoneal injection of IC261 to HCCLM3 xenograft models inhibited tumor growth. Taken together, our data indicated that IC261 has therapeutic potential for HCC.

Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8+T cells in hepatocellular carcinoma using multiplex quantitative analysis.

BACKGROUND: Fibrinogen-like protein 1 (FGL1)-Lymphocyte activating gene 3 (LAG-3) pathway is a promising immunotherapeutic target and has synergistic effect with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1). However, the prognostic significance of FGL1-LAG-3 pathway and the correlation with PD-L1 in hepatocellular carcinoma (HCC) remain unknown. METHODS: The levels of LAG-3, FGL1, PD-L1 and cytotoxic T (CD8+T) cells in 143 HCC patients were assessed by multiplex immunofluorescence. Associations between the marker's expression and clinical significances were studied. RESULTS: We found FGL1 and LAG-3 densities were elevated while PD-L1 and CD8 were decreased in HCC tissues compared to adjacent normal liver tissues. High levels of FGL1 were strongly associated with high densities of LAG-3+cells but not PD-L1. CD8+ T cells densities had positive correlation with PD-L1 levels and negative association with FGL1 expression. Elevated densities of LAG-3+cells and low levels of CD8+ T cells were correlated with poor disease outcome. Moreover, LAG-3+cells deteriorated patient stratification based on the abundance of CD8+ T cells. Patients with positive PD-L1 expression on tumor cells (PD-L1 TC+) tended to have an improved survival than that with negative PD-L1 expression on tumor cells (PD-L1 TC-). Furthermore, PD-L1 TC- in combination with high densities of LAG-3+cells showed the worst prognosis, and PD-L1 TC+ patients with low densities of LAG-3+cells had the best prognosis. CONCLUSIONS: LAG-3, FGL1, PD-L1 and CD8 have distinct tissue distribution and relationships with each other. High levels of LAG-3+cells and CD8+ T cells represent unfavorable and favorable prognostic biomarkers for HCC respectively.

Cobalt-Based MOF-on-MOF Two-Dimensional Heterojunction Nanostructures for Enhanced Oxygen Evolution Reaction Electrocatalytic Activity.

Two-dimensional (2D) Co-based MOF-on-MOF heterojunction nanostructures with improved electrocatalytic activity were successfully constructed via a mild two-step solution route, employing Co2+ ions as the center atoms, and 1,4-benzenedicarboxylate (BDC) and 4,4'-biphenyldicarboxylate (BPDC) as ligands. The as-obtained heterojunction nanostructures were characterized by field-emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, Brunauer-Emmett-Teller (BET) surface area analysis, thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS) technologies. Electrochemical measurements showed that as-prepared Co-BPDC/Co-BDC heterojunction nanostructures presented markedly enhanced OER electrocatalytic activity, compared with single Co-BPDC, Co-BDC, and/or their physical mixture. Also, the Co-BPDC/Co-BDC-3 heterojunction prepared after treatment for 3 h exhibited the strongest catalytic activity. To reach the current density jgeo = 10 mA cm-2, the Co-BPDC/Co-BDC-3 heterojunction-modified glassy carbon electrode required an overpotential of 335 mV in 1 M KOH, which was reduced by 57 and 93 mV, compared to the electrodes modified by Co-BDC and Co-BPDC, respectively. Simultaneously, the heterojunction catalyst also displayed better long-term stability. The improvement of the above performances should be attributed to the increased structure stability, BET surface area, ECSA, and electron transfer ability of the heterojunction.

Circulating Levels of Osteoprotegerin, Osteocalcin and Osteopontin in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

OBJECTIVE: Currently published data regarding the potential role of osteoprotegerin (OPG), osteocalcin (OCN) and osteopontin (OPN) for the discrimination between rheumatoid arthritis (RA) and osteoarthritis (OA) are contradictory. To derive a more precise evaluation, a meta-analysis was performed. METHODS: Published literatures comparing plasma/serum OPG, OCN and OPN levels between RA group and OA controls were searched in PubMed, Embase and the Cochrane Library. The Newcastle-Ottawa Scale was used to assess the study quality. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using I2. RESULTS: Nine studies including 438 RA patients and 255 OA patients were finally incorporated in the meta-analysis after examining title, type, abstracts and full text. The results showed that RA patients had higher plasma/serum OPN (pooled SMD = -2.57, 95% CI = -4.72 to -0.41) levels when compared to OA patients. No significant difference in plasma/serum OPG (pooled SMD = -0.29, 95% CI = -1.07‒0.49) and OCN (pooled SMD = -0.09, 95% CI = -0.48‒0.31) levels were found between RA patients and OA patients. Subgroup analysis indicated that plasma/serum OPG levels had no significant differences between RA patients and OA patients in Europe and Asian. CONCLUSIONS: Overall, there is no significant difference in circulating OPG and OCN levels between RA patients and OA patients. However, plasma/serum OPN level is significantly higher in RA patients compared with OA patients.

Risk of gestational diabetes mellitus in systemic lupus erythematosus pregnancy: a systematic review and meta-analysis.

BACKGROUND: It is well established that the risks of insulin resistance and diabetes mellitus are elevated in systemic lupus erythematosus (SLE) patients. However, the relationship between SLE pregnancy and gestational diabetes mellitus (GDM) is still obscure. We perform the present systematic review and meta-analysis to determine the relationship between GDM and SLE pregnancy. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, relevant studies were carefully retrieved through PubMed, Cochrane library and Web of Science, China National Knowledge Infrastructure, Wanfang database and China Biology Medicine database from inception till 30 August 2018. GDM risk ratio (RR) of pregnant SLE patients versus controls was calculated to evaluate the association between GDM and SLE. Pooled RRs and 95% confidence intervals (CIs) were calculated using random effects model by R software. RESULTS: The literature retrieval identified 339 potential studies in total, and five studies containing 3432 pregnant participants with 248 GDM events were included finally. Pooled analysis found that the risk of GDM were not significant increased in SLE patients compared to controls (RR = 1.08, 95% CI = 0.49 to 2.41, Z = 0.19 and P = 0.848). Nevertheless, meta-regression identified that glucocorticoids use and anti-double stranded DNA antibodies positive of SLE patients were positively associated with the risk of GDM. CONCLUSIONS: Our meta-analysis demonstrated that SLE pregnancy may not increase the risk of GDM, but the steroid use during pregnancy was associated with increased risk of GDM. Further large prospective and basic immunologic studies should be implemented for exploring the mechanism underlying glucocorticoids use and GDM.

A dense mapping study of six European AITD susceptibility regions in a large Chinese Han Cohort of Graves' disease.

OBJECTIVE: We aimed to investigate the six susceptibility loci of GD identified from European population in Chinese Han population and further to estimate the genetic heterogeneity of them in stratification of our GD patients. DESIGN: Dense mapping studies based on GWAS. PATIENTS: A total of 1536 GD patients and 1516 controls in GWAS stage and 1994 GD patients and 2085 controls and 5033 GD patients and 5389 controls in two replication stages. MEASUREMENTS: Based on our previous GWAS data, independently GD-associated SNPs in each region were identified by TagSNP analysis and logistic regression analysis. The association of these SNPs was investigated in 1994 GD patients and 2085 controls, and then, the significantly associated SNPs (P < 0.05) were further genotyped in a second cohort including 5033 GD patients and 5389 controls. RESULTS: After the first replication stage, four SNPs from three regions with Pfirst  < 0.05 were further selected and genotyped in another independent cohort. The association of two SNPs with GD was confirmed in combined Chinese cohorts: rs12575636 at 11q21 (Pcombined  = 7.55 × 10-11 , OR = 1.27) and rs1881145 in TRIB2 at 2p25.1 (Pcombined  = 5.59 × 10-8 , OR = 1.14). Further study disclosed no significant difference for these SNPs between GD subsets. However, eQTL data revealed that SESN3 could be a potential susceptibility gene of GD in 11q21 region. CONCLUSIONS: Out of the six susceptibility loci of GD identified from European population, two risk loci were confirmed in a large Chinese Han population. There is variability in GD genetic susceptibility in different ethnic groups. SESN3 is a potential susceptible gene of GD in 11q21.

Monolithically Integrated Microelectromechanical Systems for On-Chip Strain Engineering of Quantum Dots.

Elastic strain fields based on single crystal piezoelectric elements represent an effective way for engineering the quantum dot (QD) emission with unrivaled precision and technological relevance. However, pioneering researches in this direction were mainly based on bulk piezoelectric substrates, which prevent the development of chip-scale devices. Here, we present a monolithically integrated Microelectromechanical systems (MEMS) device with great potential for on-chip quantum photonic applications. High-quality epitaxial PMN-PT thin films have been grown on SrTiO3 buffered Si and show excellent piezoelectric responses. Dense arrays of MEMS with small footprints are then fabricated based on these films, forming an on-chip strain tuning platform. After transferring the QD-containing nanomembranes onto these MEMS, the nonclassical emissions (e.g., single photons) from single QDs can be engineered by the strain fields. We envision that the strain tunable QD sources on the individually addressable and monolithically integrated MEMS pave the way toward complex quantum photonic applications on chip.

SOS2-LIKE PROTEIN KINASE5, an SNF1-RELATED PROTEIN KINASE3-Type Protein Kinase, Is Important for Abscisic Acid Responses in Arabidopsis through Phosphorylation of ABSCISIC ACID-INSENSITIVE5.

Abscisic acid (ABA) plays an essential role in seed germination. In this study, we demonstrate that one SNF1-related protein kinase3-type protein kinase, SOS2-like protein kinase5 (PKS5), is involved in ABA signal transduction via the phosphorylation of an interacting protein, abscisic acid-insensitive5 (ABI5). We found that pks5-3 and pks5-4, two previously identified PKS5 superactive kinase mutants with point mutations in the PKS5 FISL/NAF (a conserved peptide that is necessary for interaction with SOS3 or SOS3-like calcium binding proteins) motif and the kinase domain, respectively, are hypersensitive to ABA during seed germination. PKS5 was found to interact with ABI5 in yeast (Saccharomyces cerevisiae), and this interaction was further confirmed in planta using bimolecular fluorescence complementation. Genetic studies revealed that ABI5 is epistatic to PKS5. PKS5 phosphorylates a serine (Ser) residue at position 42 in ABI5 and regulates ABA-responsive gene expression. This phosphorylation was induced by ABA in vivo and transactivated ABI5. Expression of ABI5, in which Ser-42 was mutated to alanine, could not fully rescue the ABA-insensitive phenotypes of the abi5-8 and pks5-4abi5-8 mutants. In contrast, mutating Ser-42 to aspartate rescued the ABA insensitivity of these mutants. These data demonstrate that PKS5-mediated phosphorylation of ABI5 at Ser-42 is critical for the ABA regulation of seed germination and gene expression in Arabidopsis (Arabidopsis thaliana).

Localized Surface Plasmons Selectively Coupled to Resonant Light in Tubular Microcavities.

Vertical gold nanogaps are created on microtubular cavities to explore the coupling between resonant light supported by the microcavities and surface plasmons localized at the nanogaps. Selective coupling of optical axial modes and localized surface plasmons critically depends on the exact location of the gold nanogap on the microcavities, which is conveniently achieved by rolling up specially designed thin dielectric films into three-dimensional microtube cavities. The coupling phenomenon is explained by a modified quasipotential model based on perturbation theory. Our work reveals the coupling of surface plasmon resonances localized at the nanoscale to optical resonances confined in microtubular cavities at the microscale, implying a promising strategy for the investigation of light-matter interactions.

The comparison of adductor canal block with femoral nerve block following total knee arthroplasty: a systematic review with meta-analysis.

PURPOSE: Although several studies have compared the clinical efficacy of an adductor canal block (ACB) to that of a femoral nerve block (FNB) for analgesia after total knee arthroplasty (TKA), disputes mainly exist in the recovery of quadriceps strength and mobilization ability between the two methods. The aim of the present study was to compare, in a systematic review and meta-analysis, the clinical efficacy of ACB with that of FNB. METHODS: We systematically searched randomized controlled trials comparing FNB with ACB for analgesia after TKA in Pubmed and the Cochrane Library from inception to April 30th 2015. There was no limitation of publication language. Trial quality was assessed using the modified Jadad scale, and eligible data were pooled for meta-analysis. RESULTS: Five studies of 348 patients were included. Outcomes showed that patients who received ACB had similar or better recovery of quadriceps strength and mobilization ability than those that underwent FNB. Similar efficacy was found between the two strategies regarding adductor strength, pain scores [at rest (p = 0.86), at or after knee flexion (p = 0.31)], opioid consumption (p = 0.99), opioid-associated adverse effects (p = 0.60), length of hospital stay (p = 0.42), patient satisfaction (p = 0.57), and success rate of blockade (p = 0.20). CONCLUSIONS: The present study suggests that TKA patients who receive ACB can achieve similar or even better recovery of quadriceps strength and mobilization ability than those treated with FNB. Taken as a whole, ACB may be a better analgesia strategy after TKA at present.