Ultra-broadband on-chip power splitters for arbitrary ratios on silicon-on-insulator.

We propose and demonstrate on-chip power splitters based on adiabatic rib waveguide enabling arbitrary splitting ratios on a monolithic silicon photonic platform. The devices are elaborately engineered based on adiabatic directional couplers with a trapezoid-structure in the longitudinal direction in the mode evolution region. The measurement results indicate that the proposed devices can achieve over 150 nm bandwidth for arbitrary splitting ratios of 50%:50%, 70%:30% and 90%:10%. The mode evolution footprint is greatly narrowed to below 79 µm with an insertion loss of less than 0.22 dB. The demonstrated arbitrary ratio power splitters offer a promising application prospect in high-density photonic integrated circuits.

High resolution, high channel count silicon arrayed waveguide grating router on-chip.

A 32×32 100 GHz silicon photonic integrated arrayed waveguide grating router (AWGR) is experimentally demonstrated for dense wavelength division multiplexing (DWDM) applications. The dimension of the AWGR is 2.57 mm×1.09 mm with a core size of 1.31 mm×0.64 mm. It exhibits 6.07 dB maximum channel loss non-uniformity with -1.66 dB best-case insertion loss and average channel crosstalk of -15.74 dB. In addition, in the case of 25 Gb/s signals, the device successfully realizes high-speed data routing. The AWG router provides clear optical eye diagrams and low power penalty at bit-error-rates of 10-9.

Compact, ultrabroadband and temperature-insensitive arbitrary ratio power splitter based on adiabatic rib waveguides.

We propose a compact, ultrabroadband and temperature-insensitive adiabatic directional coupler based on rib silicon waveguide-enabling arbitrary splitting ratios. Simulation results show that the device can achieve arbitrary splitting ratios from 1400 to 1600 nm, equal to 50%:50%, 60%:40%, 70%:30%, 80%:20%, and 90%:10% for the fundamental transverse electric mode. The designed device has an excess loss of less than 0.19 dB on the operational waveband. Furthermore, the proposed device shows a great robustness to fabrication imperfection, with a waveguide width deviation of 50 nm and ambient temperature change from 0°C to 200°C. These properties make the design a potential candidate for ultrahigh-density photonic integration chips.

High-efficiency and CMOS compatible out-of-plane light emission based on a silicon coupler.

Photonic antennas are critical in applications such as spectroscopy, photovoltaics, optical communications, holography, and sensors. Metal antennas are widely used because of their small size, but they are difficult to be compatible with a CMOS. All-dielectric antennas are easier to integrate with Si waveguides, but are generally larger in size. In this paper, we propose the design of a small-sized, high-efficiency semicircular dielectric grating antenna. The antenna's key size is only 2.37µm×4.74µm, and the emission efficiency reaches over 64% in the wavelength range from 1.16 to 1.61 µm. The antenna provides a new, to the best of our knowledge, approach for three-dimensional optical interconnections between different decks of integrated photonic circuits.

Silicon modulator based on omni junctions by effective 3D Monte-Carlo method.

3D doping structure has significant advantages in modulation efficiency and loss compared with 2D modulator doping profiles. However, to the best of our knowledge, previous work on 3D simulation methods for interdigitated doping designs applied simplified models, which prohibited complex 3D doping. In this work, innovative omni junctions, based on the effective 3D Monte-Carlo method, are believed to be the first proposed for high-performance modulators. Simulation results show that the modulation efficiency reaches 0.88 V·cm, while the loss is only 16 dB/cm, with capacitance below 0.42 pF/mm. This work provides a modulator design with superior modulation efficiency and serviceability for high-speed datacom.

Comparison between endoscopic submucosal tunnel dissection and endoscopic submucosal dissection for superficial neoplasia at esophagogastric junction: a case-matched controlled study of a single center from China.

BACKGROUND: So far, little evidence is available for the comprehensive comparison of endoscopic submucosal tunnel dissection (ESTD) with endoscopic submucosal dissection (ESD) for the treatment of superficial neoplasia at esophagogastric junction (EGJ). METHODS: EGJ superficial neoplasia patients with ESTD treatment between January, 2021 and August, 2020 were retrospectively reviewed and individually matched at 1:1 ratio with those with ESD treatment according to lesion size, specimen area and lesion location, forming ESTD and ESD group, respectively. A sample size of 17 patients was collected for each group. Treatment outcomes including resection time, specimen area, and resection speed as well as occurrence of complications were evaluated. RESULTS: Compared with ESD group, ESTD group got shorter resection time (111.00 ± 11.70 min for ESD group vs. 71.59 ± 6.18 min for ESTD group, p = 0.008) and faster section speed (0.23 ± 0.03 cm2/min for ESD group vs. 0.37 ± 0.06 cm2/min for ESTD group, p = 0.012). No complication was found to occur in ESTD group, while 1 patient with MP damage and 1 with delayed bleeding was found in ESD group. CONCLUSION: For the treatment of EGJ superficial neoplasia, ESTD is a safer and more effective and reliable endoscopic technique compared with ESD.

Comparative efficiency and safety of insulin degludec/aspart with insulin glargine in type 2 diabetes: a meta-analysis of randomized controlled trials.

Recent studies have found compared with insulin glargine (IGlar), insulin degludec/aspart (IDeg/Asp) may provide adequate glycemic control and prevent hypoglycemia events in type 2 diabetes mellitus (T2DM). Consequently, we performed a meta-analysis to appraise and compare the efficiency and safety of IDeg/Asp and IGlar in the treatment of T2DM. We sought the databases including PubMed, Embase, Scopus, Cochrane library to confirm related articles which inspected the effect of IDeg/Asp versus IGlar for the treatment of T2DM until May 2021. Finally, six randomized controlled trials (RCTs) of 1,346 patients were included. The results showed that IDeg/Asp significantly decreased the mean hemoglobin A1c (HbA1c) level but was prone to serious adverse events, and IGlar increased the nocturnal confirmed hypoglycemia events. Besides, there were no significant changes in other indicators, including mean fasting plasma glucose (FPG) level, nine-point self-measured plasma glucose (SMPG) level, and adverse events. What's more, we found that there was no significant difference in the occurrence of hypoglycemia overall, but our subgroup analysis of confirmed hypoglycemia revealed the population in this subgroup (duration of diabetes ≤11 years) might has its particularity effecting the hypoglycemia outcome. Concerning efficiency, IDeg/Asp may have advantages in controlling the mean HbA1c level. Regarding safety, IGlar might increase the risk of nocturnal confirmed hypoglycemia. Further evidence is needed to compare better the efficiency and safety of IDeg/Asp versus IGlar therapy.

Blinatumomab-induced T cell activation at single cell transcriptome resolution.

BACKGROUND: Bi-specific T-cell engager (BiTE) antibody is a class of bispecific antibodies designed for cancer immunotherapy. Blinatumomab is the first approved BiTE to treat acute B cell lymphoblastic leukemia (B-ALL). It brings killer T and target B cells into close proximity, activating patient's autologous T cells to kill malignant B cells via mechanisms such as cytolytic immune synapse formation and inflammatory cytokine production. However, the activated T-cell subtypes and the target cell-dependent T cell responses induced by blinatumomab, as well as the mechanisms of resistance to blinatumomab therapy are largely unknown. RESULTS: In this study, we performed single-cell sequencing analysis to identify transcriptional changes in T cells following blinatumomab-induced T cell activation using single cells from both, a human cell line model and a patient-derived model of blinatumomab-mediated cytotoxicity. In total, the transcriptome of 17,920 single T cells from the cell line model and 2271 single T cells from patient samples were analyzed. We found that CD8+ effector memory T cells, CD4+ central memory T cells, naïve T cells, and regulatory T cells were activated after blinatumomab treatment. Here, blinatumomab-induced transcriptional changes reflected the functional immune activity of the blinatumomab-activated T cells, including the upregulation of pathways such as the immune system, glycolysis, IFNA signaling, gap junctions, and IFNG signaling. Co-stimulatory (TNFRSF4 and TNFRSF18) and co-inhibitory (LAG3) receptors were similarly upregulated in blinatumomab-activated T cells, indicating ligand-dependent T cell functions. Particularly, B-ALL cell expression of TNFSF4, which encodes the ligand of T cell co-stimulatory receptor TNFRSF4, was found positively correlated with the response to blinatumomab treatment. Furthermore, recombinant human TNFSF4 protein enhanced the cytotoxic activity of blinatumomab against B-ALL cells. CONCLUSION: These results reveal a target cell-dependent mechanism of T-cell activation by blinatumomab and suggest that TNFSF4 may be responsible for the resistant mechanism and a potential target for combination therapy with blinatumomab, to treat B-ALL or other B-cell malignancies.

Endoscopic versus surgical resection in the management of gastric schwannomas.

BACKGROUND AND AIMS: Gastric schwannoma (GS) is not well clinically recognized and surgical resection (SR) remains the mainstay of treatment. Recently, endoscopic resection (ER) appears to be a safe and effective alternative. However, its comparative outcomes with SR is lacking. Our aim was to first compare clinical outcomes and costs between ER and SR in the management of GSs. METHODS: A total of 46 consecutive patients with GSs who underwent ER (n = 16) or SR (n = 30) in our large tertiary center between July 2007 and Oct 2018 were included. Clinicopathologic features, clinical outcomes, medical costs and follow-up were retrospectively reviewed and compared between two groups. RESULTS: Baseline characteristics are comparable except for a smaller tumor size in ER group (22.9 vs 41.0 mm, p = 0.002). Complete resection was achieved in 87.5% of patients with ER and 100% of patients with SR (p = 0.116). The ER group had a significant shorter operative time (91.6 vs 128.2 min), less blood loss (16.9 vs 62.7 mL) and lower operation cost (21,054.4 vs 30,843.4 RMB) than SR group (all p < 0.05). There was no significant difference in adverse events (12.5% vs 10%, p = 0.812) and length of postoperative hospital stay (8.3 vs 8.2 days, p = 0.945). During a long-term follow-up of mean 37.4 months (range 6-140 months), no residue, recurrence or metastasis was observed in both groups. CONCLUSIONS: Compared with SR, ER has the similar safety and efficacy in the management of GSs, but contributes to a shorter operation time and lower medical costs. ER may be considered as the first-line treatment, especially for patients with GSs smaller than 30 mm.

Compact, broadband, and low-loss silicon photonic arbitrary ratio power splitter using adiabatic taper.

The arbitrary ratio power splitter is widely used in photonic integrated circuits (PICs), for signal monitoring, power equalization, signal feedback, and so on. Here we designed a fabrication-tolerant, compact, broadband, and low-loss arbitrary ratio power splitter. The proposed arbitrary ratio power splitter was realized with an adiabatically tapered silicon rib waveguide with 70 nm shallow etches and an Si3N4 waveguide. The fabrication analysis confirmed that both of them are robust to fabrication errors. 3D finite-difference time-domain simulations show a very low excess loss (less than 0.02 dB for Si3N4 waveguide and 0.05 dB for Si rib waveguide), and a broadband operating wavelength range (100 nm). Good fabrication tolerance and standard critical dimensions make the arbitrary ratio power splitter compatible with the standard fabrication process of commercial silicon photonic foundries.

Broadband and CMOS compatible polarization splitter-rotator based on a bi-level taper.

A silicon-on-insulator polarization diversity scheme is proposed. Based on an asymmetrical evanescent coupler, a broadband and compact polarization splitter-rotator comprising mode conversion tapers and mode sorting asymmetric Y junctions is optimized with silicon dioxide upper cladding and a silicon nitride waveguide. The simulation results show mode conversion loss is less than 0.2 dB, and the extinction ratio is lower than -17dB in the wavelength range of 1.48µm to 1.67µm.

Variations in the insulin receptor substrate 1 (IRS1) and its association with growth traits in Chinese black Tibetan sheep (Ovis aries).

This paper presented the results on the study of insulin receptor substrate 1 (IRS1) polymorphisms in Chinese black Tibetan sheep. Via DNA direct sequencing, four variations within 3' untranslated region (UTR) of IRS1, including g.9382T > G, g.9569T > G, g.9572C > T and g.9695A > C were detected in the black Tibetan sheep population. Based on the χ2 test, those four loci deviated from Hardy-Weinberg equilibrium (p < 0.05). In g.9569T > G locus, genotype of GG possessed advantage on body weight (p < 0.05). In g.9572C > T locus, individuals with genotype of TT homozygous mutation decreased significantly on body weight, withers height, body length and chest circumference (p < 0.05 or p < 0.01). In g.9695A > C locus, the body weight and chest circumference were also higher in AA carriers than in CC carriers (p < 0.05). Our results provided evidence that polymorphisms in IRS1 were associated with growth efficiency traits by quantitative genetic analysis, and may be used for marker-assisted selection in Chinese indigenous sheep.

Values of Radial Artery Provocation Tests at Different Doses of Ergonovine in the Diagnosis of Coronary Artery Spasm.

The intracoronary drug provocation test has been the gold standard for diagnosis of coronary artery spasm (CAS); however, it has been identified with severe complications. In this study, we investigated the sensitivity, specificity, and safety of radial artery provocation test at different doses of ergonovine in the diagnosis of CAS. This study enrolled 57 patients, which were then divided into CAS group (n = 24) and control group (n = 33) after intracoronary ergonovine provocation test. All patients underwent radial artery provocation test at different doses of ergonovine. The predictive values of radial artery provocation test for the diagnosis of CAS were analyzed using receiver operator characteristic curve. In the radial artery provocation test at different doses of ergonovine, radial artery stenosis degree was all found to be significantly higher in the CAS group than in the control group (all P < 0.001). In the control group, significant differences were noted in the radial artery stenosis degree between different doses of ergonovine (all P < 0.05). In the CAS group, the radial artery stenosis degree was significantly higher in 160 µg and 100 µg of ergonovine than in 60 µg of ergonovine (all P < 0.001). The radial artery provocation test at 60 µg and 100 µg of ergonovine did not cause CAS, chest pain, and ECG ischemic changes. In the radial artery provocation test at 160 µg of ergonovine, some patients had CAS, chest pain, and ECG ischemic changes. The specificity and sensitivity of radial artery provocation test were 90.91% and 50.00% at 60 µg of ergonovine, 96.97% and 66.67% at 100 µg of ergonovine, and 90.91% and 95.83% at 160 µg of ergonovine for the diagnosis of CAS. As per our findings, we can conclude that the basic tension of radial artery increases in the CAS group. With the increase of ergonovine doses, its sensitivity and specificity improve, but its safety decreases. We will explore the most optimal dose of ergonovine in future studies.

Hsa-miRNA-23a-3p promotes atherogenesis in a novel mouse model of atherosclerosis.

Of the known regulators of atherosclerosis, miRNAs have been demonstrated to play critical roles in lipoprotein homeostasis and plaque formation. Here, we generated a novel animal model of atherosclerosis by knocking in LDLRW483X in C57BL/6 mice, as the W483X mutation in LDLR is considered the most common newly identified pathogenic mutation in Chinese familial hypercholesterolemia (FH) individuals. Using the new in vivo mouse model combined with a well-established atherosclerotic in vitro human cell model, we identified a novel atherosclerosis-related miRNA, miR-23a-3p, by microarray analysis of mouse aortic tissue specimens and human aortic endothelial cells (HAECs). miR-23a-3p was consistently downregulated in both models, which was confirmed by qPCR. Bioinformatics analysis and further validation experiments revealed that the TNFα-induced protein 3 (TNFAIP3) gene was the key target of miR-23a-3p. The miR-23a-3p-related functional pathways were then analyzed in HAECs. Collectively, the present results suggest that miR-23a-3p regulates inflammatory and apoptotic pathways in atherogenesis by targeting TNFAIP3 through the NF-κB and p38/MAPK signaling pathways.

Advances in computational approaches in identifying synergistic drug combinations.

Accumulated empirical clinical experience, supported by animal or cell line models, has initiated efforts of predicting synergistic combinatorial drugs with more-than-additive effect compared with the sum of the individual agents. Aiming to construct better computational models, this review started from the latest updated data resources of combinatorial drugs, then summarized the reported mechanism of the known synergistic combinations from aspects of drug molecular and pharmacological patterns, target network properties and compound functional annotation. Based on above, we focused on the main in silico strategies recently published, covering methods of molecular modeling, mathematical simulation, optimization of combinatorial targets and pattern-based statistical/learning model. Future thoughts are also discussed related to the role of natural compounds, drug combination with immunotherapy and management of adverse effects. Overall, with particular emphasis on mechanism of action of drug synergy, this review may serve as a rapid reference to design improved models for combinational drugs.

Endoscopic submucosal excavation and endoscopic full-thickness resection for gastric schwannoma: five-year experience from a large tertiary center in China.

BACKGROUND AND AIMS: Endoscopic resection (ER) is an effective and safe method for gastric submucosal tumors, mostly composed of gastrointestinal stromal tumors and leiomyomas. The role of ER in gastric schwannoma (GS) has rarely been described. Our aim was to evaluate the efficacy and safety of ER for GS. METHODS: This is a retrospective study in consecutive patients who underwent ER for GS from March 2013 to October 2018 at our center. Clinicopathological, endoscopic, and follow-up data were collected and analyzed. RESULTS: A total of 16 consecutive patients (9 females, 56.3%) were included, with a mean age of 50.4 years (range 25-75 years). The mean tumor size was 22.9 ± 15.1 mm (range 10-55 mm). Thirteen tumors (81.3%) were located in the middle third of the stomach and 12 tumors (75%) grew with intraluminal pattern. Endoscopic submucosal excavation (ESE) was performed in 7 patients while endoscopic full-thickness resection (EFTR) was done in 9 patients. R0 resection was achieved in 14 patients (87.5%). The mean operative time was 91.6 ± 52.8 min (range 36-203 min) and the mean postoperative length of hospital stays was 8.3 ± 2.7 days (range 6-13 days). No adverse events were encountered except for fevers in 2 patients. No patients required surgical resection or intervention. During long-term follow-up of mean 21.8 months (range 6-62 months), no residue, recurrence, or metastasis was observed. CONCLUSIONS: ER is effective and safe for patients with GS with favorable long-term outcomes.

Compact multimode waveguide based temperature-insensitive Mach-Zehnder interferometer.

A novel multimode waveguide based Mach-Zehnder interferometer (MZI) is demonstrated on an SOI platform with the properties of compact footprint and temperature-insensitive operation. The device can achieve a thermal dependence around 13pm/°C in a wavelength range of 40nm. Owing to the utilization of one single straight multimode waveguide, the device is naturally immune to local temperature distributions. The measured results exhibit transmissions with an extinction ratio better than 8dB and a minimum insertion loss lower than 0.31dB over the wavelength range of 1545nm-1585nm. Moreover, the proposed device is compatible with CMOS process.

Application of the aza-Diels-Alder reaction in the synthesis of natural products.

The Diels-Alder reaction that involves a nitrogen atom in the diene or dienophile is termed the aza-Diels-Alder reaction. As well as the powerful all-carbon Diels-Alder reaction, the aza-Diels-Alder reaction has also played an important role in the total synthesis of natural products. Herein, we review various natural products using an aza-Diels-Alder reaction as a key step to their total synthesis, and divide the syntheses into inter- and intra-molecular aza-Diels-Alder reactions and a retro-aza-Diels-Alder reaction. Inter- and intra-molecular aza-Diels-Alder reactions involve an imine as an electron deficient dienophile and an imine as an electron deficient azadiene. The significance of the aza-Diels-Alder reaction for the construction of a six-membered ring containing nitrogen is tremendous, but the development of asymmetric, in particular catalytic enantioselective intramolecular aza-Diels-Alder reaction in the total synthesis of natural products remains highly challenging, and will no doubt see enormous advances in the future.

Switch-on fluorescent strategy based on crystal violet-functionalized CdTe quantum dots for detecting L-cysteine and glutathione in water and urine.

The concentration of L-cysteine (Cys) and glutathione (GSH) is closely related to the critical risk of various diseases. In our study, a new rapid method for the determination of Cys and GSH in water and urine samples has been developed using a fluorescent probe technique, which was based on crystal violet (CV)-functionalized CdTe quantum dots (QDs). The original QDs emitted fluorescence light, which was turned off upon adding CV. This conjugation of CV and QDs could be attributed to electrostatic interaction between COO- of mercaptopropionic acid (MPA) on the surface of QDs and N+ of CV in aqueous solution. In addition, Förster resonance energy transfer (FRET) also occurred between CdTe QDs and CV. After adding Cys or GSH to the solution, Cys or GSH exhibited a stronger binding preference toward Cd2+ than Cd2+-MPA, which disturbed the interaction between MPA and QDs. Thus, most MPA was able to be separated from the surface of QDs because of the participation of Cys or GSH. Then, the fluorescence intensity of the CdTe QDs was enhanced. Good linear relationships were obtained in the range of 0.02-40 µg mL-1 and 0.02-50 µg mL-1, and the detection limits were calculated as 10.5 ng mL-1 and 8.2 ng mL-1, for Cys and GSH, respectively. In addition, the concentrations of biological thiols in water and urine samples were determined by the standard addition method using Cys as the standard; the quantitative recoveries were in the range of 97.3-105.8%, and relative standard deviations (RSDs) ranged from 2.5 to 3.7%. The method had several unique properties, such as simplicity, lower cost, high sensitivity, and environmental acceptability. Graphical abstract Crystal violet-functionalized CdTe quantum dots for detecting L-cysteine and glutathione with switch-on fluorescent strategy.

Routing light with ultrathin nanostructures beyond the diffraction limit.

An open nanostructure consisting of a periodic chain of subwavelength-nanoparticles for compressing and routing light beyond the diffraction limit is proposed. The open nanostructure is ultrathin and compact, with a size much smaller than the wavelength of light. We demonstrate that our ultrathin open nanostructure provides functions that can route and manipulate light at the subwavelength scale and can also sharply bend and split light beams below the diffraction limit while exhibiting broadband, incident-angle-tolerant, and robust against disorder. A physical picture based on all-angle self-collimation is presented to understand the manipulation of light using the ultrathin open nanostructure. Experimental and numerical observations validate our findings. This approach provides great flexibility in the design of nanophotonic devices for routing and manipulating light beyond the diffraction limit.