Monolithic tunable dual-wavelength laser utilizing erbium-doped lithium niobate on an insulator.

We demonstrate a monolithic tunable dual-wavelength laser fabricated on erbium-doped lithium niobate on an insulator (Er:LNOI). The dual-wavelength laser enables independent tuning with a continuously linear electro-optic (EO)-modulated tuning range of 11.875 GHz at a tuning efficiency of 0.63 pm/V. Tunable microwave generation within 50 GHz with a maximum extinction ratio of 35 dB is experimentally demonstrated by further exploring the charge accumulation effect in LNOI. The monolithic design of this work paves the way for microscale integration of laser devices, presenting significant prospects in photonics research and applications.

Endothelial-immune crosstalk contributes to vasculopathy in nonalcoholic fatty liver disease.

The top cause of mortality in patients with nonalcoholic fatty liver disease (NAFLD) is cardiovascular complications. However, mechanisms of NAFLD-associated vasculopathy remain understudied. Here, we show that blood outgrowth endothelial cells (BOECs) from NAFLD subjects exhibit global transcriptional upregulation of chemokines and human leukocyte antigens. In mouse models of diet-induced NAFLD, we confirm heightened endothelial expressions of CXCL12 in the aortas and the liver vasculatures, and increased retention of infiltrated leukocytes within the vessel walls. To elucidate endothelial-immune crosstalk, we performed immunoprofiling by single-cell analysis, uncovering T cell intensification in NAFLD patients. Functionally, treatment with a CXCL12-neutralizing antibody is effective at moderating the enhanced chemotactic effect of NAFLD BOECs in recruiting CD8+ T lymphocytes. Interference with the CXCL12-CXCR4 axis using a CXCR4 antagonist also averts the impact of immune cell transendothelial migration and restores endothelial barrier integrity. Clinically, we detect threefold more circulating damaged endothelial cells in NAFLD patients than in healthy controls. Our work provides insight into the modulation of interactions with effector immune cells to mitigate endothelial injury in NAFLD.

Reconstruction of Inferior Vena Cava by Autologous Great Saphenous Vein Grafts in Liver Surgery.

BACKGROUND: To secure surgical margin for hepatic lesion with involvement of the inferior vena cava (IVC), combined radical liver resection and IVC replacement are required. A novel method of replacing IVC by newly customized autologous great saphenous vein (GSV) grafts was introduced by this study. This study aimed at reporting the feasibility and outcome of this novel technique. METHODS: From January 2014 to January 2021, all consecutive patients who underwent concomitant hepatectomy and IVC replacement by autogenous GSV graft were enrolled in this study. Technical insights, intraoperative details, demographic data, postoperative complication, graft patency and survival data were collected and analyzed. RESULTS: Concomitant hepatectomy/autotransplantation (ERAT) with IVC replacement by autogenous GSV graft was successful in 47 patients and there was no 30-day mortality. There were 8 out of the 47 patients whose retrohepatic venae cavae were completely invaded by the lesion and their reconstructed IVCs were totally made from GSV grafts. The other 39 patients whose IVCs were partially invaded had their IVCs reconstructed by both the unaffected part of the IVC wall and newly customized GSV graft. Postoperative complications classified as Clavien-Dindo grade II, III A and III B were observed in 10, 7 and 3 patients, respectively. The median follow-up months were 35 months (29-80 months). No patient developed thrombosis of the graft and 100% patency of the IVC was observed throughout the study. CONCLUSION: In selected patients, hepatectomy/ERAT with IVC replacement by autogenous GSV graft is safe and feasible. The newly customized autologous GVS graft was ideal for reconstruction of the IVC in liver surgery.

Retroconversion of estrogens into androgens by bacteria via a cobalamin-mediated methylation.

Steroid estrogens modulate physiology and development of vertebrates. Conversion of C19 androgens into C18 estrogens is thought to be an irreversible reaction. Here, we report a denitrifying Denitratisoma sp. strain DHT3 capable of catabolizing estrogens or androgens anaerobically. Strain DHT3 genome contains a polycistronic gene cluster, emtABCD, differentially transcribed under estrogen-fed conditions and predicted to encode a cobalamin-dependent methyltransferase system conserved among estrogen-utilizing anaerobes; an emtA-disrupted DHT3 derivative could catabolize androgens but not estrogens. These data, along with the observed androgen production in estrogen-fed strain DHT3 cultures, suggested the occurrence of a cobalamin-dependent estrogen methylation to form androgens. Consistently, the estrogen conversion into androgens in strain DHT3 cell extracts requires methylcobalamin and is inhibited by propyl iodide, a specific inhibitor of cobalamin-dependent enzymes. The identification of the cobalamin-dependent estrogen methylation thus represents an unprecedented metabolic link between cobalamin and steroid metabolism and suggests that retroconversion of estrogens into androgens occurs in the biosphere.

Hyaluronidase-1-mediated glycocalyx impairment underlies endothelial abnormalities in polypoidal choroidal vasculopathy.

BACKGROUND: Polypoidal choroidal vasculopathy (PCV), a subtype of age-related macular degeneration (AMD), is a global leading cause of vision loss in older populations. Distinct from typical AMD, PCV is characterized by polyp-like dilatation of blood vessels and turbulent blood flow in the choroid of the eye. Gold standard anti-vascular endothelial growth factor (anti-VEGF) therapy often fails to regress polypoidal lesions in patients. Current animal models have also been hampered by their inability to recapitulate such vascular lesions. These underscore the need to identify VEGF-independent pathways in PCV pathogenesis. RESULTS: We cultivated blood outgrowth endothelial cells (BOECs) from PCV patients and normal controls to serve as our experimental disease models. When BOECs were exposed to heterogeneous flow, single-cell transcriptomic analysis revealed that PCV BOECs preferentially adopted migratory-angiogenic cell state, while normal BOECs undertook proinflammatory cell state. PCV BOECs also had a repressed protective response to flow stress by demonstrating lower mitochondrial functions. We uncovered that elevated hyaluronidase-1 in PCV BOECs led to increased degradation of hyaluronan, a major component of glycocalyx that interfaces between flow stress and vascular endothelium. Notably, knockdown of hyaluronidase-1 in PCV BOEC improved mechanosensitivity, as demonstrated by a significant 1.5-fold upregulation of Krüppel-like factor 2 (KLF2) expression, a flow-responsive transcription factor. Activation of KLF2 might in turn modulate PCV BOEC migration. Barrier permeability due to glycocalyx impairment in PCV BOECs was also reversed by hyaluronidase-1 knockdown. Correspondingly, hyaluronidase-1 was detected in PCV patient vitreous humor and plasma samples. CONCLUSIONS: Hyaluronidase-1 inhibition could be a potential therapeutic modality in preserving glycocalyx integrity and endothelial stability in ocular diseases with vascular origin.

Monolithic coherent LABS lidar based on an integrated transceiver array.

We demonstrate a monolithic frequency-modulated continuous-wave (FMCW) lidar chip with an integrated transceiver array based on lens-assisted beam steering (LABS) technology. It enables beam emitting, steering, receiving, and coherent detecting on a single chip with simultaneous distance and velocity detection. An integrated transceiver is designed with a composite structure of a Bragg grating in the middle and a U-shaped photodetector (PD) surrounding it. For a proof-of-concept demonstration, a chip with 2 × 2 switchable transceiver array is fabricated. A monolithic coherent LABS lidar system with a scanning angle of 2.86° and a scanning speed of 5.3 µs is implemented for 5 m ranging and 0.45 m/s velocity detection.

Epigenomes of Human Hearts Reveal New Genetic Variants Relevant for Cardiac Disease and Phenotype.

RATIONALE: Identifying genetic markers for heterogeneous complex diseases such as heart failure is challenging and requires prohibitively large cohort sizes in genome-wide association studies to meet the stringent threshold of genome-wide statistical significance. On the other hand, chromatin quantitative trait loci, elucidated by direct epigenetic profiling of specific human tissues, may contribute toward prioritizing subthreshold variants for disease association. OBJECTIVE: Here, we captured noncoding genetic variants by performing epigenetic profiling for enhancer H3K27ac chromatin immunoprecipitation followed by sequencing in 70 human control and end-stage failing hearts. METHODS AND RESULTS: We have mapped a comprehensive catalog of 47 321 putative human heart enhancers and promoters. Three thousand eight hundred ninety-seven differential acetylation peaks (FDR [false discovery rate], 5%) pointed to pathways altered in heart failure. To identify cardiac histone acetylation quantitative trait loci (haQTLs), we regressed out confounding factors including heart failure disease status and used the G-SCI (Genotype-independent Signal Correlation and Imbalance) test1 to call out 1680 haQTLs (FDR, 10%). RNA sequencing performed on the same heart samples proved a subset of haQTLs to have significant association also to gene expression (expression quantitative trait loci), either in cis (180) or through long-range interactions (81), identified by Hi-C (high-throughput chromatin conformation assay) and HiChIP (high-throughput protein centric chromatin) performed on a subset of hearts. Furthermore, a concordant relationship between the gain or disruption of TF (transcription factor)-binding motifs, inferred from alternative alleles at the haQTLs, implied a surprising direct association between these specific TF and local histone acetylation in human hearts. Finally, 62 unique loci were identified by colocalization of haQTLs with the subthreshold loci of heart-related genome-wide association studies datasets. CONCLUSIONS: Disease and phenotype association for 62 unique loci are now implicated. These loci may indeed mediate their effect through modification of enhancer H3K27 acetylation enrichment and their corresponding gene expression differences (bioRxiv: https://doi.org/10.1101/536763). Graphical Abstract: A graphical abstract is available for this article.

Positive intervention effect of mobile health application based on mindfulness and social support theory on postpartum depression symptoms of puerperae.

OBJECTIVE: This study investigated the effects of mobile health application designed based on mindfulness and social support theory on parenting self-efficacy and postpartum depression symptoms of puerperae. METHODS: We recruited 130 puerperae from a hospital in China and randomized them to an App use group (n = 65) and a waiting control group (n = 65). The App group underwent an 8-week app use intervention while the control group underwent no intervention. We measured four main variables (mindfulness, perceived social support, maternal parental self-efficacy and postpartum depressive symptoms) before and after the App use intervention. RESULTS: In the App group, perceived social support, maternal parental self-efficacy were significantly higher and postpartum depressive symptoms was significantly lower. In the control group, there were no significant differences in any of the four variables between the pre-test and post-test. CONCLUSIONS: Our findings indicated that the mobile health application may help to improve perceived social support, maternal self-efficacy and reduce postpartum depressive symptoms. The finding of the mobile health application's effect extends our understanding of integrative effects of mindfulness and perceived social support on reduction of postpartum depressive symptoms and suggests clinical potentials in the treatment of postpartum depressive symptoms.

Single-Cell Transcriptome of Wet AMD Patient-Derived Endothelial Cells in Angiogenic Sprouting.

Age-related macular degeneration (AMD) is a global leading cause of visual impairment in older populations. 'Wet' AMD, the most common subtype of this disease, occurs when pathological angiogenesis infiltrates the subretinal space (choroidal neovascularization), causing hemorrhage and retinal damage. Gold standard anti-vascular endothelial growth factor (VEGF) treatment is an effective therapy, but the long-term prevention of visual decline has not been as successful. This warrants the need to elucidate potential VEGF-independent pathways. We generated blood out-growth endothelial cells (BOECs) from wet AMD and normal control subjects, then induced angiogenic sprouting of BOECs using a fibrin gel bead assay. To deconvolute endothelial heterogeneity, we performed single-cell transcriptomic analysis on the sprouting BOECs, revealing a spectrum of cell states. Our wet AMD BOECs share common pathways with choroidal neovascularization such as extracellular matrix remodeling that promoted proangiogenic phenotype, and our 'activated' BOEC subpopulation demonstrated proinflammatory hallmarks, resembling the tip-like cells in vivo. We uncovered new molecular insights that pathological angiogenesis in wet AMD BOECs could also be driven by interleukin signaling and amino acid metabolism. A web-based visualization of the sprouting BOEC single-cell transcriptome has been created to facilitate further discovery research.

Monolithic transceiver for lens-assisted beam-steering Lidar.

We demonstrate a monolithic transceiver based on a CMOS-compatible silicon photonic platform for lens-assisted beam-steering (LABS) light detecting and ranging (Lidar) application. By implementing an on-chip two-dimensional transceiver array and off-chip lens, beam emitting, steering, and receiving are realized simultaneously on a single chip. The transceiver is designed with a structure of a U-shaped vertical Ge photodetector surrounding a grating for high-efficiency light transmission and reception. The on-chip photodetector has a bandwidth of 87 MHz, a responsivity of 0.3A/W, and a detection sensitivity of -20dBm. For proof-of-concept demonstration, a time-of-flight Lidar system is achieved for target ranging with a detection distance of 5.2 m, a scanning angle of 2.86°, and a scanning speed of 5.3µs . This work demonstrates a feasible solution to integrated Lidar with beam emitting and receiving on one single chip based on LABS.

Single-frequency integrated laser on erbium-doped lithium niobate on insulator.

The erbium-doped lithium niobate on insulator (Er:LNOI) platform has great promise in the application of telecommunication, microwave photonics, and quantum photonics, due to its excellent electro-optic, piezo-electric, nonlinear nature, as well as the gain characteristics in the telecommunication C-band. Here, we report a single-frequency Er:LNOI integrated laser based on a dual-cavity structure. Facilitated by the Vernier effect and gain competition, the single-frequency laser can operate stably at 1531 nm wavelength with a 1484 nm pump laser. The output laser has a power of 0.31 µW, a linewidth of 1.2 MHz, and a side mode suppression ratio of 31 dB. Our work allows the direct integration of this laser source with existing LNOI components and paves the way for a fully integrated LNOI system.

Prognostic factors of non-muscle invasive bladder cancer: a study based on next-generation sequencing.

OBJECTIVE: To investigate the genetic prognostic factors for the recurrence of non-muscle invasive bladder cancer. MATERIALS AND METHODS: The patients underwent transurethral resection of bladder tumor and received bacillus Calmette-Guérin (BCG) or epirubicin. Next-generation sequencing was performed and alterations of genes, pathways, and tumor mutation burden were recorded. Associations between these clinicopathological and genetic variants were estimated, and prognostic factor identified. RESULTS: A total of 58 cases were included in our study, and 46 patients underwent treatment with BCG. FGFR3 was the most frequently altered gene (48%), and more commonly detected in intermediate-risk patients. Univariate Cox analysis demonstrated that 10 genes were significantly correlated with BCG failure, while NEB, FGFR1 and SDHC were independent recurrence predictors. Besides, epigenetic-related gene pathway mutations were negatively correlated with recurrence (hazard ratio: 0.198, P = 0.023). DNA damage response and repair gene alterations were positively correlated with tumor burden, while altered TP53 was most frequent among these genes and significant correlated with high tumor burden. CONCLUSION: BCG instillation significantly reduced the rate of recurrence compared with epirubicin in this population. Potential biomarkers and therapeutic targets were found with the help of next-generation sequencing; correlations between DDR genes alterations and high tumor mutation burden were also demonstrated.

Association between preoperative serum albumin and prognosis in patients with adrenocortical carcinoma after primary resection: a retrospective study.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a poor prognosis. Given the limited treatment options, prognostic assessment of ACC is increasingly crucial. In this study, we aim to assess the correlation between preoperative serum albumin and prognosis in patients with ACC after primary resection. METHODS: We retrospectively collected and reviewed medical information about 71 ACC patients who underwent primary resection. Survival analysis was performed by Kaplan-Meier analysis with log-rank test or Breslow test. Receiver operating characteristic (ROC) curve and Jordan index was generated to explore optimal cut-off value of albumin. Univariate and multivariate analysis was conducted using Cox's hazards model. Statistical significance was defined as P < 0.05. RESULTS: Among included patients, 33 patients (46.5%) relapsed at the end of follow-up, while 39 patients (54.9%) died. The median overall survival (OS) of included patients was 17 (range 1-104) months, and median recurrence-free survival (RFS) was 10 (range 0-104) months. In univariate analysis, the albumin was significantly associated with OS (HR:0.491, 95% CI: 0.260-0.930, P = 0.029) and RFS (HR: 0.383, 95% CI: 0.192-0.766, P = 0.007). In multivariate analysis, serum albumin as an independent prognostic factor of OS was confirmed (HR: 0.351, 95% CI: 0.126-0.982, P = 0.046). CONCLUSIONS: Preoperative albumin might be a significant prognostic factor for ACC patients after primary resection. This result may be useful for risk stratification and management of this rare malignancy.

Benefit of Postoperative Radiotherapy for Patients With Nonmetastatic Adrenocortical Carcinoma: A Population-Based Analysis.

BACKGROUND: Adrenocortical carcinoma (ACC) is an aggressive cancer with high recurrence rates and poor prognosis, even after radical surgery. The survival benefit of adjuvant radiotherapy (RT) in patients with ACC has not been well explored. The aim of this study was to evaluate the effect of adjuvant RT on the survival outcome of patients with ACC. PATIENTS AND METHODS: All patients with nonmetastatic ACC who underwent complete resection were identified from the SEER database (2004-2016). Overall survival (OS) was estimated using the Kaplan-Meier method. Multivariable Cox regression analysis was performed to identify prognostic factors associated with survival. RESULTS: Of 365 patients with nonmetastatic ACC, 55 (15.1%) received adjuvant RT and the remainder underwent surgery alone. Patient characteristics were similar between the 2 groups, but those with a higher disease stage were more likely to receive adjuvant RT. Overall, patients receiving RT seemed to have better survival compared with the non-RT group (3-year OS rate, 63.1% vs 52.8%; P<.062). After adjustment for confounding factors, adjuvant RT was indeed associated with a 48% decreased risk of death (hazard ratio, 0.52; 95% CI, 0.29-0.91; P=.023) for all patients. In addition, adjuvant RT may confer a survival benefit only in patients with a high risk of recurrence (3-year OS rate, 55.1% vs 40.0%; P=.048) rather than in those with low/moderate-risk ACC (P=.559). CONCLUSIONS: Our findings suggest that adjuvant RT may be associated with improved survival in patients with nonmetastatic ACC who underwent radical surgery, especially those with high risk of recurrence.

Adrenal Surgery for Synchronously Metastatic Adrenocortical Carcinoma: A Population-Based Analysis.

BACKGROUND: Metastatic adrenocortical carcinoma (ACC) is an aggressive cancer with poor prognosis, with limited treatment options. The survival benefit of adrenal surgery in patients with synchronous metastatic disease has not been well explored. METHODS: Patients with ACC with synchronous metastases were identified from the Surveillance, Epidemiology, and End Results database (2010-2016). The effect of adrenal surgery on different patterns of distant metastases was assessed. The overall survival was estimated by the Kaplan-Meier method. Multivariable Cox regression analysis was performed to identify prognostic factors associated with survival outcome. RESULTS: A total of 202 patients with synchronous metastatic ACC were identified from the SEER database, 76 (37.6%) patients underwent adrenal surgery. Compared to nonsurgical patients, patients who underwent adrenal surgery had a better survival (median overall survival: 4 vs. 13 months, P < 0.001). In sub-analyses, except for patients with liver metastases (P = 0.670), adrenalectomy could consistently confer a significant survival benefit in patients with lung metastases (P = 0.003), bone metastases (P = 0.020), and multiple metastases (P = 0.002). Cox regression analysis revealed that in addition to adrenalectomy [hazard ratio (HR) = 0.64, 95% confidence interval (CI) 0.45-0.92; P = 0.017], metastasectomy (HR = 0.48, 95% CI 0.26-0.86; P = 0.013), and chemotherapy (HR = 0.59, 95% CI 0.42-0.82; P = 0.002) were also associated with improved survival. CONCLUSIONS: Our findings support the view that adrenal surgery may be associated with improved survival in patients with synchronous metastatic ACC (except for patients with liver metastases), and the metastatic sites have significant prognostic implications on survival outcomes with adrenal surgery.

Changes in the characteristics of dental emergencies under the influence of SARS-CoV-2 pandemic: a retrospective study.

BACKGROUND: Further understanding of the distribution and changing characteristics of dental diseases is of great significance for all dental emergency centers for strengthening the medical staff's treatment knowledge abilities and effective use of emergency resources in the face of public health emergencies involving highly infectious respiratory diseases. METHODS: The medical records of 4158 dental emergency patients in 2019 and 2020 were retrospectively analyzed and divided into pre-SARS-COV-2 group and SARS-COV-2 group according to time. The demographic data, date and time, diagnosis, and treatment methods of the two groups were statistically described, and the chi-squared test was used to analyze the differences. The medical records of 4158 dental emergency patients during the same period of two years in 2019 and 2020 were retrospectively analyzed and divided into SARS-COV-2 pre-group and SARS-COV-2 group according to time. The demographic data, date and time, diagnosis and treatment methods of the two groups were statistically described, and the chi-square test was used to determine the differences. RESULTS: During the SARS-COV-2 pandemic, the number of dental emergency visits increased by 29.7%. During the pandemic, males (n = 286, 58.1%) were more likely to visit dental emergency centers for trauma than females (n = 206, 41.9%) (P < 0.05); females (n = 242, 60.8%) were more likely to visit dental emergency centers for acute gingivitis and acute pericoronitis than males (n = 156, 39.2%) (P < 0.05). A major change in diagnosis was related to acute pulpitis (K04.0) and acute apical periodontitis (K04.4), which increased by 9.2%; acute gingivitis (K05.0) and acute pericoronitis (K05.2) increased by 3.5%; open wound of the lip and oral cavity (S01.5) decreased by 17.9%; other conditions (non-emergency diseases) increased by 6.8%, compared with the pre-SARS-COV-2 period. Among the treatment modalities, during the pre-SARS-COV-2 period, 304 patients (17.7%) received a prescription for antibiotics and analgesics, and 1485 (86.5%) received a prescription for local treatment. During the SARS-COV-2 period, 958 (39.2%) received a prescription for antibiotics and analgesics, and 1636 (67.0%) received a prescription for local treatment. CONCLUSION: SARS-COV-2 pandemic led to changes in the characteristics of dental emergency patients. Trauma, acute pulpitis, and acute periodontitis are the leading reasons patients refer to dental emergency centers. Dental emergency centers should optimize treatment procedures, optimize the staff, and reasonably allocate materials according to the changes to improve the on-site treatment capacity and provide adequate dental emergency care.

[Study of the Relationship between Oral Diseases and Depression Symptoms in Middle-Aged and Older Adult Populations in China-A Retrospective Study Based on CHARLS Data].

OBJECTIVE: To study the relationship between oral disease and depressive symptoms in middle-aged and older adult populations in China. METHODS: The data from the China Health and Retirement Longitudinal Study (CHARLS) done between 2013 and 2015 were analyzed. A total of 3828 middle-aged and older adults showing no depressive symptoms in an assessment with the 10-item Centre for Epidemiological Studies Depression Scale (CES-D-10) were selected as the subjects of observation, and oral disease was taken as the dependent variable. Changes in depressive symptoms in the population were tracked in 2015, and the Cox proportional hazards model was used to estimate the relationship between oral diseases and depressive symptoms. RESULTS: The detection rate of depressive symptoms was 29.3% in middle-aged and older adults with oral diseases, and that of middle-aged and older adults without oral diseases was 20.4%, the difference being statistically significant ( P<0.001). After controlling for confounding factors, Cox proportional hazards model analysis found an association between oral diseases and depressive symptoms (hazard ratio [ HR]=0.683, 95% confidence interval [ CI]: 0.583-0.800). It was more likely for middle-aged and older women ( HR=0.708, 95% CI: 0.573-0.874) with oral diseases to develop depressive symptoms than men ( HR=0.644, 95% CI: 0.506-0.819) did ( P<0.05). CONCLUSION: Oral diseases in the middle-aged and older adult populations tended to lead to depressive symptoms, and women showed higher rate than men did. Prevention and control measures should be taken actively in the course of oral disease treatment to promote mental health of middle-aged and older adults.

Zwitterionic Polymer Conjugated Glucagon-like Peptide-1 for Prolonged Glycemic Control.

Glucagon-like peptide-1 (GLP-1) is of particular interest for treating type 2 diabetes mellitus (T2DM), as it induces insulin secretion in a glucose-dependent fashion and has the potential to facilitate weight control. However, native GLP-1 is a short incretin peptide that is susceptible to fast proteolytic inactivation and rapid clearance from the circulation. Various GLP-1 analogs and bioconjugation of GLP-1 analogs have been developed to counter these issues, but these modifications are frequently accompanied by the sacrifice of potency and the induction of immunogenicity. Here, we demonstrated that with the conjugation of a zwitterionic polymer, poly(carboxybetaine) (pCB), the pharmacokinetic properties of native GLP-1 were greatly enhanced without serious negative effects on its potency and secondary structure. The pCB conjugated GLP-1 further provided glycemic control for up to 6 days in a mouse study. These results illustrate that the conjugation of pCB could realize the potential of using native GLP-1 for prolonged glycemic control in treating T2DM.

Deterministic single-soliton generation in a graphene-FP microresonator.

Dissipative Kerr solitons (DKS) in high-Q microresonators have attracted considerable attention for their broadband optical frequency combs and ultra-short pulse generation. Owing to thermal effects, complicated tuning strategies are required to generate and sustain the single-soliton state in microresonators. In this paper, we propose a novel microresonator scheme based on the Fabry-Pérot fiber resonator and single-layer graphene saturable absorber (SA) and demonstrate that this design allows deterministic single-soliton generation without frequency tuning and has strong robustness against pump perturbation. The soliton range and thermal instability of the proposed device are also discussed. This work facilitates a novel nonlinear platform connecting high-Q microresonators and conventional SA-assisted mode-locking operations.

Primary tumour resection for synchronously metastatic phaeochromocytoma and paraganglioma: A population-based study.

CONTEXT: Until recently, there are few effective treatment options for patients with synchronous metastatic phaeochromocytoma (PHEO) and paraganglioma (PGL). Surgical resection may improve the survival outcomes of these patients. OBJECTIVE: To assess the role of surgical resection of the primary tumour in patients with synchronous metastatic PHEO and PGL. DESIGN: Retrospective analysis of patients with synchronous metastatic PHEO/PGL using the Surveillance, Epidemiology, and End Results database (1988-2016). PATIENTS: Patients with synchronous metastatic PHEO/PGL who underwent primary tumour resection. MEASUREMENTS: Overall survival and Cox regression analyses. RESULTS: A total of 99 patients with metastatic PHEO and 127 metastatic PGL patients were identified from the SEER database. Compared to metastatic PHEO, metastatic PGL patients had a better overall survival (5-year survival rate: 33.3% vs. 49.0%, p = .001). In metastatic PHEO patients, 53 (53.5%) patients underwent surgery for primary site. Surgically treated patients had an improved survival compared to non-surgery patients (5-year survival rate: 50.9% vs. 29.6%, p = .017). Among metastatic PGL patients, primary tumour resection was performed in 74 (58.3%) patients and had no significant effect on the survival of metastatic PGL. In sub-analyses, surgery only conferred a survival benefit in patients with primary tumours originated from aortic/carotid bodies, rather than other sites or abdominal tumours. CONCLUSION: Our findings suggest that primary tumour resection is associated with improved survival in patients with synchronous metastatic PHEO and those with PGL diseases located in aortic/carotid bodies. In addition, PHEO and PGL should be treated as two distinct clinical entities.