Downregulation of ceramide synthase 1 promotes oral cancer through endoplasmic reticulum stress

C18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma.However,the function of ceramide synthase 1,a key enzyme in C18 ceramide synthesis,in oral squamous cell carcinoma is still unclear.The aim of our study was to investigate the relationship between ceramide synthase 1 and oral cancer.In this study,we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell lines.In a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide,ceramide synthase 1 knockout was associated with the severity of oral malignant transformation.Immunohistochemical studies showed significant upregulation of PCNA,MMP2,MMP9,and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area.In addition,ceramide synthase 1 knockdown promoted cell proliferation,migration,and invasion in vitro.Overexpression of CERS1 obtained the opposite effect.Ceramide synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA upregulation.Activating transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional upregulation.In addition,mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin resistance.Taken together,our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance.

Self-calibrating microring synapse with dual-wavelength synchronization

As a resonator-based optical hardware in analog optical computing, a microring synapse can be straightforwardly configured to simulate the connection weights between neurons, but it faces challenges in precision and stability due to cross talk and environmental perturbations. Here, we propose and demonstrate a self-calibration scheme with dual-wavelength synchronization to monitor and calibrate the synaptic weights without interrupting the computation tasks. We design and fabricate an integrated 4 × 4 microring synapse and deploy our self-calibration scheme to validate its effectiveness. The precision and robustness are evaluated in the experiments with favorable performance, achieving 2-bit precision improvement and excellent robustness to environmental temperature fluctuations(the weights can be corrected within 1 s after temperature changes 0.5°C). Moreover, we demonstrate matrix inversion tasks based on Newton iterations beyond 7-bit precision using this microring synapse. Our scheme provides an accurate and real-time weight calibration independently parallel from computations and opens up new perspectives for precision boost solutions to large-scale analog optical computing.

A simplified method for investigating the bending behavior of piles supporting embankments on soft ground

In recent years,concrete and reinforced concrete piles have been widely used to stabilize soft ground under embankments.Previous research has shown that bending failure,particularly during rapid filling on soft ground,is the critical failure mode for pile-supported embankments.Here,we propose an efficient two-stage method that combines a test-verified soil deformation mechanism and Poulos’solution for pile–soil interaction to investigate the bending behavior of piles supporting embankments on soft ground.The results reveal that there are three possible bending failure scenarios for such piles:at the interface between the soft and firm ground layers,at mid-depths of the fan zone,and at the boundary of the soil deformation mechanism.The location of the bending failure depends on the position and relative stiffness of the given pile.Furthermore,the effect of embedding a pile into a firm ground layer on the bending behavior was investigated.When the embedded length of a pile exceeded a critical value,the bending moment at the interface between the soft and firm ground layers reached a limiting value.In addition,floating piles that are not embedded exhibit an overturning pattern of movement in the soft ground layer,and a potential failure is located in the upper part of these piles.

Nanomedicine integrating the lipidic derivative of 5-fluorouracil,miriplatin and PD-L1 si RNA for enhancing tumor therapy

Immunosuppressive microenvironments present critical problems in clinical chemotherapy.To regulate the tumor immune microenvironment for enhancing antitumor effect,a combination of immune checkpoint inhibitors(ICIs)with chemotherapeutics has been applied clinically.In this study,miriplatin(MiPt),the lipidic derivative of 5-fluorouracil(Fu-OA),as well as the programmed death ligand 1(PD-L1)target si RNA(siPD-L1)were integrated into Lip-Pt/Fu@siPD-L1 nanoparticles(NPs)for chemo-immunotherapy.In vitro results showed that Lip-Pt/Fu@siPD-L1 NPs could exhibit effective siRNA gene silencing and promote the phagocytosis of tumor cells by macrophages.Furthermore,in vivo results revealed that LipPt/Fu@siPD-L1 NPs showed significantly higher anti-tumor efficiency than that of the physical mixing of Mi Pt,5-fluorouracil,and Lip@siPD-L1 NPs(delivery of siPD-L1 by liposomes).The best anti-tumor efficiency of Lip-Pt/Fu@siPD-L1 NPs resulted from the synergistic immunotherapeutic effects of Mi Pt and siPD-L1 based on the inhibition of CD47 expression and the downregulation of PD-L1 in tumor cells,which elicited a robust anti-tumor immune response through the activation of macrophage phagocytosis and immune checkpoint inhibition.The Lip-Pt/Fu@siPD-L1 NPs provide a potential strategy for tumor chemo-immunotherapy.

Ultra-flat dispersion in an integrated waveguide with five and six zero-dispersion wavelengths for mid-infrared photonics

We propose a new type of dispersion flattening technology, which can generate an ultra-flat group velocity dispersion profile with five and six zero-dispersion wavelengths(ZDWs). The dispersion value varies from-0.15 to 0.35 ps/(nm·km) from 4 to 8 μm, which to the best of our knowledge is the flattest one reported so far, and the dispersion flatness is improved by more than an order of magnitude. We explain the principle of producing six ZDWs. Mode distribution in this waveguide is made stable over a wide bandwidth. General guidelines to systematically control the dispersion value, sign, and slope are provided, and one can achieve the desired dispersion by properly adjusting the structural parameters. Fabrication tolerance of this waveguide is also examined.

A small microring array that performs large complex-valued matrix-vector multiplication

As an important computing operation,photonic matrix-vector multiplication is widely used in photonic neutral networks and signal processing.However,conventional incoherent matrix-vector multiplication focuses on real-valued operations,which cannot work well in complex-valued neural networks and discrete Fourier transform.In this paper,we propose a systematic solution to extend the matrix computation of microring arrays from the real-valued field to the complex-valued field,and from small-scale(i.e.,4×4)to large-scale matrix computation(i.e.,16×16).Combining matrix decomposition and matrix partition,our photonic complex matrix-vector multiplier chip can support arbitrary large-scale and complex-valued matrix computation.We further demonstrate Walsh-Hardmard transform,discrete cosine transform,discrete Fourier transform,and image convolutional processing.Our scheme provides a path towards breaking the limits of complex-valued computing accelerator in conventional incoherent optical architecture.More importantly,our results reveal that an integrated photonic platform is of huge potential for large-scale,complex-valued,artificial intelligence computing and signal processing.

Broadband athermal waveguides and resonators for datacom and telecom applications

The high-temperature sensitivity of the silicon material index limits the applications of silicon-based micro-ring resonators in integrated photonics. To realize a low but broadband temperature-dependent-wavelength-shift microring resonator, designing a broadband athermal waveguide becomes a significant task. In this work,we propose a broadband athermal waveguide that shows a low effective thermo-optical coefficient of1 × 10^(-6)∕K from 1400 to 1700 nm. The proposed waveguide shows a low-loss performance and stable broadband athermal property when it is applied to ring resonators, and the bending loss of ring resonators with a radius of >30 μm is 0.02 dB/cm.

Robust cavity soliton formation with hybrid dispersion

Microresonator-based Kerr frequency combs have attracted a great deal of attention in recent years, in which mode locking of the generated combs is associated with bright or dark cavity soliton formation. In this paper,we show that, different from soliton propagation along a waveguide, cavity solitons can be robustly formed under a unique dispersion profile with four zero-dispersion wavelengths. More importantly, such a dispersion profile exhibits much smaller overall dispersion, thus making it possible to greatly reduce the pump power by five to six times.

Six-hierarchy model of accident analysis and its application in coal mine accidents

Accident analysis models play a significant role in accident investigation and analysis.Most traditional models,usually based on a chain of events,have serious limitations when used for complex systems,especially for coal mine accident.HFACS is a widely accepted accident cause model with complex structure and content.Based on HFACS and accident investigation need in China,a new systemic accident analysis method“Six-hierarchy model”is proposed.And the index database of accident causal factors at each hierarchy of coal mine accidents is established.This model provides clear guidance for the prevention of accidents from six levels,which helps to the targeted rectification after accidents and the improvement of safety management level.The source,ap-plication scope,advantages and disadvantages of HFACS and six-hierarchy model are compared.The“2.14”gas explosion accident in Sunjiawan coal mine is analyzed by using HFACS and six-hierarchy model and the safety management suggestions are put forward.The study shows that the Six-hierarchy model provides a clear guide for the prevention of accidents from six levels.And it benefits the targeted rectification after accidents and the continuous improvement of safety management.

Numerical simulation of smoke stratification in tunnel fires under longitudinal velocities

Use of the longitudinal critical velocity in tunnel fires may destroy the stratification of smoke downstream,which is not conducive to the evacuation of downstream tunnel users.Reducing the longitudinal velocity can maintain stratification,but the appropriate longitudinal velocity range is unknown.Stratification of smoke under the longitudinal velocity is studied using Fire Dynamics Simulator(FDS).The aims of this paper are to explore the relationship between the longitudinal velocity and smoke stratification and to obtain a proper velocity range that can maintain clear downstream stratification.Based on Newman's theory,the"stratification velocity"is proposed,which is the maximum velocity that maintains downstream smoke stratification.A good correspondence between the average Froude number within 200 m downstream and the longitudinal velocity and heat release rate(HRR)is found.The correlation between the temperature stratification and Froude number is obtained.Fr=0.49 can be used to distinguish whether the stratification is clear.The relationship between the critical velocity and the stratification velocity is also discussed.

Robust generation of frequency combs in a microresonator with strong and narrowband loss

Octave-spanning frequency comb generation in microresonators is promising, but strong spectral losses caused by material absorption and mode coupling between two polarizations or mode families can be detrimental. We examine the impact of the spectral loss and propose robust comb generation with a loss of even 300 dB/cm.Cavity nonlinear dynamics show that a phase change associated with spectral losses can facilitate phase matching and Kerr comb generation. Given this unique capability, we propose a novel architecture of on-chip spectroscopy systems.