High-Purity Generation and Switching of Twisted Single Photons.

Quantum technologies, if scaled into a high-dimensional Hilbert space, can dramatically enhance connection capabilities with supporting higher bit rates and ultrasecure information transfer. Twisted single photons, carrying orbital angular momentum (OAM) as an unbounded dimension, could address the growing demand for high-dimensional quantum information encoding and transmission. By hybrid integration of two-dimensional semiconductor WSe_{2} with a spin-orbit-coupled microring resonator, we demonstrate an integrated tunable twisted single photon source with the ability to precisely define and switch between highly pure spin-OAM states. Our results feature a single photon purity of g^{(2)}(0)∼0.13 with a cavity-enhanced quantum yield of 76% and a high OAM mode purity up to 96.9%. Moreover, the demonstrated quantum-chiral control can also enable new quantum functionality such as single photon routing for efficient quantum information processing on chip.

Proteomic Profiling and Tumor Microenvironment Characterization Reveal Molecular and Immunological Hallmarks of Left-Sided and Right-Sided Colon Cancer Tumorigenesis.

Left-sided and right-sided colon cancer (LSCC and RSCC) display different biological and clinical characteristics. However, the differences in their tumorigenesis and tumor microenvironment remain unclear. In this study, we profiled the proteomic landscapes of LSCC and RSCC with data-independent acquisition mass spectrometry (DIA-MS) using fresh tumor and adjacent normal tissues from 24 patients. A total of 7403 proteingroups were primarily identified with DIA-MS. After quality control, 7212 proteingroups were used for further analysis. Through comparing the difference in proteomic profiles between LSCC and RSCC samples, 2556 commonly and 1982 region-type-specific regulated proteingroups were characterized. During the development of LSCC and RSCC, metabolic, growth, cell division, cell adhesion, and migration pathways were found to be significantly dysregulated (P < 0.05), which was further confirmed by transcriptome data from TCGA. Compared to RSCC, most parts of the immune-related signatures, immune cell infiltration scores, and overall immune scores of LSCC were higher. The systematic elucidation of proteomic and transcriptomic profiles in this work improves our understanding of tumorigenesis and immune microenvironment characteristics of LSCC and RSCC.

Two-Dimensional Reconfigurable Non-Hermitian Gauged Laser Array.

Topological effects in photonic non-Hermitian systems have recently led to extraordinary discoveries including nonreciprocal lasing, topological insulator lasers, and topological metamaterials, to mention a few. These effects, although realized in non-Hermitian systems, are all stemming from their Hermitian components. Here we experimentally demonstrate the topological skin effect and boundary sensitivity, induced by the imaginary gauge field in a two-dimensional laser array, which are fundamentally different from any Hermitian topological effects and intrinsic to open systems. By selectively and asymmetrically injecting gain into the system, we have synthesized an imaginary gauge field on chip, which can be flexibly reconfigured on demand. We show not only that the non-Hermitian topological features remain intact in a nonlinear nonequilibrium system, but also that they can be harnessed to enable persistent phase locking with intensity morphing. Our work lays the foundation for a dynamically reconfigurable on-chip coherent system with robust scalability, attractive for building high-brightness sources with arbitrary intensity profiles.

Topological quadratic-node semimetal in a photonic microring lattice.

Graphene, with its two linearly dispersing Dirac points with opposite windings, is the minimal topological nodal configuration in the hexagonal Brillouin zone. Topological semimetals with higher-order nodes beyond the Dirac points have recently attracted considerable interest due to their rich chiral physics and their potential for the design of next-generation integrated devices. Here we report the experimental realization of the topological semimetal with quadratic nodes in a photonic microring lattice. Our structure hosts a robust second-order node at the center of the Brillouin zone and two Dirac points at the Brillouin zone boundary-the second minimal configuration, next to graphene, that satisfies the Nielsen-Ninomiya theorem. The symmetry-protected quadratic nodal point, together with the Dirac points, leads to the coexistence of massive and massless components in a hybrid chiral particle. This gives rise to unique transport properties, which we demonstrate by directly imaging simultaneous Klein and anti-Klein tunnelling in the microring lattice.

Topological Photonic Lattice for Uniform Beam Splitting, Robust Routing, and Sensitive Far-Field Steering.

Far-field optical beam steering is a fast-growing technology for communications, spatial ranging, and detections. Nonmechanical optical phased arrays based on straight waveguides have been studied recently, where the beam emission angle to the propagation axis can be scanned by conveniently tuning the wavelength. However, the dispersion of the waveguide limits the wavelength sensitivity of beam steering and the deliberately created emitters inevitably introduce in-line backscattering on-chip. To overcome these limitations, here, we report a robust and back-reflection-free topological photonic integrated circuit, where different functionalities, such as beam splitting, routing, and far-field steering, are defined by strategic arrangements of lattices with different topological modulations simply controlled by a single lattice deformation parameter. Benefiting from the robust topological scheme, an extra band flattening is applied to achieve far-field steering with high wavelength sensitivity.

Spin-orbit microlaser emitting in a four-dimensional Hilbert space.

A step towards the next generation of high-capacity, noise-resilient communication and computing technologies is a substantial increase in the dimensionality of information space and the synthesis of superposition states on an N-dimensional (N > 2) Hilbert space featuring exotic group symmetries. Despite the rapid development of photonic devices and systems, on-chip information technologies are mostly limited to two-level systems owing to the lack of sufficient reconfigurability to satisfy the stringent requirement for 2(N - 1) degrees of freedom, intrinsically associated with the increase of synthetic dimensionalities. Even with extensive efforts dedicated to recently emerged vector lasers and microcavities for the expansion of dimensionalities1-10, it still remains a challenge to actively tune the diversified, high-dimensional superposition states of light on demand. Here we demonstrate a hyperdimensional, spin-orbit microlaser for chip-scale flexible generation and manipulation of arbitrary four-level states. Two microcavities coupled through a non-Hermitian synthetic gauge field are designed to emit spin-orbit-coupled states of light with six degrees of freedom. The vectorial state of the emitted laser beam in free space can be mapped on a Bloch hypersphere defining an SU(4) symmetry, demonstrating dynamical generation and reconfiguration of high-dimensional superposition states with high fidelity.

Ultrafast heterodyne mode imaging and refractive index mapping of a femtosecond laser written multimode waveguide.

We demonstrate imaging of individual modes in a femtosecond laser written multimode waveguide by spatial-heterodyne interferometry and decomposition in data post-processing. Despite the spatial and temporal overlap between multiple waveguide modes, we show the extraction of amplitude for each individual mode and their corresponding temporal dynamics. The mode imaging scheme is effective with the presence of intermodal interference and can be prospective for sensing of ultrafast phase and refractive index fluctuations. We also reconstruct the two-dimensional transverse refractive index map of the multimode waveguide leveraging all the imaged modes and substantiate the reconstructed index map by simulation.

Analysis of risk factors and prognosis of 253 lymph node metastasis in colorectal cancer patients.

BACKGROUND: This study aimed to explore potential risk factors for 253 lymph node metastasis, and to identify the prognostic impact of 253 lymph node metastasis in colorectal cancer patients. METHODS: A retrospective study was conducted of 391 colorectal cancer patients who underwent surgical treatments that included 253 lymph node dissection. Clinicopathological features, molecular indexes and 1-year overall survival rates were analyzed. RESULTS: Univariate analyses revealed the following risk factors for 253 lymph node metastasis: high preoperative levels of CEA, large tumour max diameters, and numbers of harvested lymph nodes, presence of vessel carcinoma emboli, low level of MSH6 and MLH1 immunohistochemical staining intensity. Multivariate analysis showed that elevated MLH1 immunohistochemical staining intensity was an independent protective factor for 253 lymph node metastasis (OR: 0.969, 95% CI 0.945, 0.994, P = 0.015). A significant difference was found in 1-year overall survival rate between 253 lymph node-positive and lymph node-negative colorectal cancer patients (88.9% vs.75.0%, P < 0.001). CONCLUSIONS: 253 lymph node-positive colorectal cancer patients had a worse prognosis than the 253 lymph node-negative patients. 253 lymph node dissection may improve the prognosis of colorectal cancer patients with high risk factors for 253 lymph node metastasis.

The effect of different inferior mesenteric artery ligation levels and different lymph node dissection areas on the short- and long-term outcomes of rectal cancer.

BACKGROUND: Surgery is the most effective treatment for rectal cancer patients, but its key steps, including selection of the level of inferior mesenteric artery ligation and removal of 253 lymph nodes, are still inconclusive. This study aimed to analyze the effects of different surgical methods, including levels of ligation (low vs. high) and lymph node dissection areas (D2 vs. D3) on the short-term and long-term outcomes. METHODS: Between March 2014 and August 2018, 253 rectal cancer patients were retrospectively analyzed; 113 patients underwent low ligation D2 lymph node dissection (LLD2), 75 patients underwent low ligation D3 lymph node dissection (LLD3), and 65 patients underwent high ligation (HL). We compared the short-term and long-term outcomes among the different groups. RESULTS: There were no significant differences among the groups in terms of the intraoperative variables, including operative time, blood transfusion, and conversion from laparoscopic to open surgery. The median blood loss was significantly lower in LLD3 (50 mL) than in LLD2 (100 mL) and HL (100 mL), but it was not significantly different between LLD2 and HL. There were no significant differences among the LLD2, LLD3, and HL groups in the incidence of postoperative complications (9.7% vs. 12.0% vs. 10.8%, respectively) and hospital stay (14 vs. 15 vs. 14, respectively). The anastomotic leakage Clavien-Dindo grade was significantly lower with LLD2 and LLD3 than with HL, but it was the same between LLD2 and LLD3. The total number of lymph nodes harvested in the LLD3 group (n=14) was higher than that in the LLD2 group (n=12), but it was not significantly different than that in the HL group (n=13). There were no significant differences among the groups in terms of 3-year overall survival rate and disease-free survival rate. CONCLUSIONS: Low ligation was similar to HL in terms of major intraoperative and postoperative parameters, but it can reduce the severity of anastomotic leakage to a certain extent. D3 lymph node dissection can increase the total number of lymph nodes harvested, but it did not improve long-term prognosis.

Higher-dimensional supersymmetric microlaser arrays.

The nonlinear scaling of complexity with the increased number of components in integrated photonics is a major obstacle impeding large-scale, phase-locked laser arrays. Here, we develop a higher-dimensional supersymmetry formalism for precise mode control and nonlinear power scaling. Our supersymmetric microlaser arrays feature phase-locked coherence and synchronization of all of the evanescently coupled microring lasers-collectively oscillating in the fundamental transverse supermode-which enables high-radiance, small-divergence, and single-frequency laser emission with a two-orders-of-magnitude enhancement in energy density. We also demonstrate the feasibility of structuring high-radiance vortex laser beams, which enhance the laser performance by taking full advantage of spatial degrees of freedom of light. Our approach provides a route for designing large-scale integrated photonic systems in both classical and quantum regimes.

Ultrafast control of fractional orbital angular momentum of microlaser emissions.

On-chip integrated laser sources of structured light carrying fractional orbital angular momentum (FOAM) are highly desirable for the forefront development of optical communication and quantum information-processing technologies. While integrated vortex beam generators have been previously demonstrated in different optical settings, ultrafast control and sweep of FOAM light with low-power control, suitable for high-speed optical communication and computing, remains challenging. Here we demonstrate fast control of the FOAM from a vortex semiconductor microlaser based on fast transient mixing of integer laser vorticities induced by a control pulse. A continuous FOAM sweep between charge 0 and charge +2 is demonstrated in a 100 ps time window, with the ultimate speed limit being established by the carrier recombination time in the gain medium. Our results provide a new route to generating vortex microlasers carrying FOAM that are switchable at GHz frequencies by an ultrafast control pulse.

The PI3K/Akt/GSK-3ß/ROS/eIF2B pathway promotes breast cancer growth and metastasis via suppression of NK cell cytotoxicity and tumor cell susceptibility.

OBJECTIVE: To examine the effect of pSer9-GSK-3ß on breast cancer and to determine whether the underlying metabolic and immunological mechanism is associated with ROS/eIF2B and natural killer (NK) cells. METHODS: We employed TWS119 to inactivate GSK-3ß by phosphorylating Ser9 and explored its effect on breast cancer and NK cells. The expression of GSK-3ß, natural killer group 2 member D (NKG2D) ligands, eIF2B was quantified by PCR and Western blot. We measured intracellular reactive oxygen species (ROS) and mitochondrial ROS using DCFH-DA and MitoSOXTM probe, respectively, and conducted quantitative analysis of cellular respiration on 4T1 cells with mitochondrial respiratory chain complex I/III kits. RESULTS: Our investigation revealed that TWS119 downregulated NKG2D ligands (H60a and Rae1), suppressed the cytotoxicity of NK cells, and promoted the migration of 4T1 murine breast cancer cells. Nevertheless, LY290042, which attenuates p-GSK-3ß formation by inhibiting the PI3K/Akt pathway, reversed these effects. We also found that higher expression of pSer9-GSK-3ß induced higher levels of ROS, and observed that abnormality of mitochondrial respiratory chain complex I/III function induced the dysfunction of GSK-3ß-induced electron transport chain, naturally disturbing the ROS level. In addition, the expression of NOX3 and NOX4 was significantly up-regulated, which affected the generation of ROS and associated with the metastasis of breast cancer. Furthermore, we found that the expression of pSer535-eIF2B promoted the expression of NKG2D ligands (Mult-1 and Rae1) following by expression of pSer9-GSK-3ß and generation of ROS. CONCLUSIONS: The PI3K/Akt/GSK-3ß/ROS/eIF2B pathway could regulate NK cell activity and sensitivity of tumor cells to NK cells, which resulted in breast cancer growth and lung metastasis. Thus, GSK-3ß is a promising target of anti-tumor therapy.

Effects of pool size and spacing on burning rate and flame height of two square heptane pool fires.

The interaction of multiple pool fires might lead to higher burning rate and flame height than single pool fire, raising the possibility of fire ignition and flame spread and increasing the risks to people, buildings and environment. To quantify the burning rate and flame height of multiple pool fires from the view of physical mechanism, this paper presents an experimental study on two identical square pool fires. Heptane was used as fuel. The pool size and spacing were varied. Results showed that both the burning rate and flame height change non-monotonically with spacing. From the view of air entrainment, a correlation for the flame height of two pool fires is developed involving pool size, spacing and the flame height of zero spacing. The comparison with experimental results shows that the developed correlation is suitable for two heptane or propane fires. A theoretical study based on energy balance at one of the pool surfaces is performed to evaluate the burning rate of two fires, which is finally expressed as a function of pool size, spacing, burning rate and the flame height of single fire. The proposed model is validated using the experimental and literature data, which presents a reasonable reliability.

IDO1 impairs NK cell cytotoxicity by decreasing NKG2D/NKG2DLs via promoting miR-18a.

BACKGROUND: Indoleamine-2,3-dioxygenase 1 (IDO1) is an important enzyme for altering the tumour microenvironment and assisting tumour cells to escape the immune system. RESULTS: In this study, a significant reduction in NK cell cytotoxicity that was associated with a high expression of IDO1 in a reconstructed tumour microenvironment was observed. In a co-culture system of tumour cell culture supernatant (TSN) and murine NK cell, IDO1 was substantially increased, while NKG2D was markedly downregulated in NK cells. Based on computational predictions, miR-18a, which has two definite binding sites consisting of the 3'UTR of NKG2D and the 3'UTR of NKG2D ligand (Mult-1), was suspected to be a negative regulator of which its conjoined. As expected, the IDO1 could promote the expression of miR-18a and promote the downregulation effect of miR-18a on NKG2D and NKG2DL, and INCB024360 (INCB) could reverse the result. For digging the mechanism deeper, we authenticated IDO1 promoted the combination of miR-18a and AGO2 after argonaute 2 (AGO2) co-immunoprecipitation, which then degraded Mult-1 mRNA and inhibited the translation of it, further destructing NK cell cytotoxicity. CONCLUSION: Our findings revealed a new regulatory axis, IDO1/miR-18a/NKG2D/NKG2DL, in the regulation of NK cell function. This may provide insight into the mechanism of the priming effect of IDO1 inhibitors and miR-18a interference, then elicit possible new methods of cancer treatment.

Downregulation of MCT4 for lactate exchange promotes the cytotoxicity of NK cells in breast carcinoma.

Monocarboxylate transporter-4 (MCT4), a monocarboxylic acid transporter, demonstrates significantly increased expression in the majority of malignancies. We performed an experiment using BALB/C mice, and our results showed that ShMCT4 transfection or the pharmaceutic inhibition of MCT4 with 7acc1 strengthens the activity of NK cells. The results of a calcein assay revealed that the cytotoxicity of NK cells was strengthened via inhibition of MCT4. In addition, ELISA testing showed that the content of perforin and CD107a was increased, and PCR amplification and immunoblotting revealed that the expression of NKG2D and H60 was upregulated after the inhibition of MCT4. Further, we observed an elevated pH value, decreased extracellular lactate flow, and attenuated tumor growth. Therefore, we concluded that the inhibition of MCT4 enhanced the cytotoxicity of NK cells by blocking lactate flux and reversing the acidified tumor microenvironment. In addition to these findings, we also discovered that MCT4 depletion may have a pronounced impact on autophagy, which was surmised by observing that the inhibition of autophagy (3MA) pulled the enhanced cytotoxicity of NK cells downwards. Together, these data suggest that the key effect of MCT4 depletion on NK cells probably utilizes inductive autophagy as a compensatory metabolic mechanism to minimize the acidic extracellular microenvironment associated with lactate export in tumors.