Irradiated engineered tumor cell-derived microparticles remodel the tumor immune microenvironment and enhance antitumor immunity.

Radiotherapy (RT), administered to roughly half of all cancer patients, occupies a crucial role in the landscape of cancer treatment. However, expanding the clinical indications of RT remains challenging. Inspired by the radiation-induced bystander effect (RIBE), we used the mediators of RIBE to mimic RT. Specifically, we discovered that irradiated tumor cell-released microparticles (RT-MPs) mediated the RIBE and had immune activation effects. To further boost the immune activation effect of RT-MPs to achieve cancer remission, even in advanced stages, we engineered RT-MPs with different cytokine and chemokine combinations by modifying their production method. After comparing the therapeutic effect of the engineered RT-MPs in vitro and in vivo, we demonstrated that tIL-15/tCCL19-RT-MPs effectively activated antitumor immune responses, significantly prolonged the survival of mice with malignant pleural effusion (MPE), and even achieved complete cancer remission. When tIL-15/tCCL19-RT-MPs were combined with PD-1 monoclonal antibody (mAb), a cure rate of up to 60% was achieved. This combination therapy relied on the activation of CD8+ T cells and macrophages, resulting in the inhibition of tumor growth and the establishment of immunological memory against tumor cells. Hence, our research may provide an alternative and promising strategy for cancers that are not amenable to conventional RT.

Characterizing mid-infrared micro-ring resonator with frequency conversion.

Due to the high cost, low-performance lasers and detectors in the mid-infrared (MIR) band, the development of MIR-integrated devices is very slow. Here, we demonstrate an effective method to characterize the parameters of MIR devices by using frequency conversion technology. We designed and fabricated rib waveguides and the micro-ring resonators (MRRs) on a silicon-on-sapphire platform. The MIR laser for the test is generated by difference frequency generation, and the transmission spectrum of the MIR-MRRs is detected by sum frequency generation. The experimental results show that the waveguide transmission loss is 4.5 dB/cm and the quality factor of the micro-ring reaches 38000, which is in good agreement with the numerical simulations. This work provides a useful method to characterize MIR integrated devices based on the frequency conversion technique, which can boost the development of MIR integrated optics in the future.

Observing multiple processes of backward-phase-matching spontaneous parametric downconversion in a single-periodic crystal.

A nonlinear process based on backward quasi-phase matching (BQPM) can be used to realize mirrorless optical parametric oscillation, the generation of paired photons with a separable joint spectral amplitude and narrow wavelength bandwidth, and the preparation of counterpropagating polarization-entangled photons, which shows distinct advantages over some applications based on forward quasi-phase matching. In this work, three types of BQPM in a bulk periodically poled potassium titanyl phosphate crystal with a single period are theoretically analyzed. Experimentally, the harmonic wave generated by second-harmonic generation in type 0 and type I exhibits a narrow bandwidth of 15.5 GHz. Furthermore, photon pairs generated by spontaneous parametric downconversion in all types of BQPM (type 0, type I, and type II) at 7th order are observed and characterized. Their coincidence-to-accidental ratios are all greater than 5 × 103 in the pump power range from 10 mW to 500 mW. This research lays the foundation for further applications of BQPM in nonlinear optics, quantum optics, and quantum information processing.

Clinical analysis of patients with primary and secondary extranodal natural killer/T-cell lymphoma of central nervous system.

Extranodal natural killer (NK)/T-cell lymphoma (NKTL) is a rare non-Hodgkin lymphoma that rarely arise exclusively in or metastasizes to the central nervous system (CNS). Globally, CNS involvement of NKTL heralds a serious prognosis and there is no standard treatment. 19 of 414 patients (4.59%) with ENKL followed were diagnosed with CNS involvement between 2006 and 2020. Two patients had primary CNS (PCNS) NKTL, and 17 patients had secondary CNS (SCNS) invasion. A total of 9 patients survived and 10 patients died. The median overall survival time was 55 months, and the median survival time after CNS invasion was 17 months. The 5-year cumulative survival probability was 45.7%. In conclusion, CNS risk evaluation and prophylaxis treatment can be carried out for patients with NK/T-cell lymphoma prognostic index risk group III/IV. In terms of treatment, systemic therapy based on methotrexate combined with radiotherapy and intrathecal chemotherapy can be selected.

Bacterial riboswitches cooperatively bind Ni(2+) or Co(2+) ions and control expression of heavy metal transporters.

Bacteria regularly encounter widely varying metal concentrations in their surrounding environment. As metals become depleted or, conversely, accrue to toxicity, microbes will activate cellular responses that act to maintain metal homeostasis. A suite of metal-sensing regulatory ("metalloregulatory") proteins orchestrate these responses by allosterically coupling the selective binding of target metals to the activity of DNA-binding domains. However, we report here the discovery, validation, and structural details of a widespread class of riboswitch RNAs, whose members selectively and tightly bind the low-abundance transition metals, Ni(2+) and Co(2+). These riboswitches bind metal cooperatively, and with affinities in the low micromolar range. The structure of a Co(2+)-bound RNA reveals a network of molecular contacts that explains how it achieves cooperative binding between adjacent sites. These findings reveal that bacteria have evolved to utilize highly selective metalloregulatory riboswitches, in addition to metalloregulatory proteins, for detecting and responding to toxic levels of heavy metals.

Orelabrutinib-bruton tyrosine kinase inhibitor-based regimens in the treatment of central nervous system lymphoma: a retrospective study.

BACKGROUND: Central nervous system lymphoma (CNSL) is an aggressive lymphoma. Orelabrutinib, an oral Bruton tyrosine kinase inhibitor, is a new treatment strategy for CNSL. This study aims to evaluate the efficacy and safety of orelabrutinib-based regimens in the treatment of patients with CNSL. METHODS: Twenty-three patients with CNSL were included in this retrospective study. All patients received the orelabrutinib-based regimen. Efficacy was evaluated based on investigators' assessment of overall response rate (ORR), complete response/unconfirmed complete response (CR/CRu), partial response (PR), stable disease (SD), progressive disease (PD), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). The safety of orelabrutinib-based regimens has also been evaluated. RESULTS: A total of 17.39% of patients received orelabrutinib-based regimens for consolidation therapy, and 82.61% of patients for induction therapy (4 newly diagnosed CNSL, 15 relapsed/refractory CNSL). In the newly diagnosed CNSL group, the ORR was 100% (1 CR, 1 CRu, 2 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 100%, 100%, and 100%, respectively. Of the 15 relapsed/refractory CNSL patients, five therapy regimens were applied (orelabrutinib, n = 3; orelabrutinib/immunotherapy, n = 3; orelabrutinib/chemotherapy, n = 2; orelabrutinib/immunochemotherapy, n = 6; orelabrutinib/radiotherapy, n = 1). The ORR was 60.00% (4 CR, 5 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 92.30%, 67.70%, and 70.00%, respectively. Twenty-one patients reported adverse events (AEs), and 6 patients experienced grade ≥ 3 AEs. CONCLUSION: Orelabrutinib-based regimens were efficacious and well-tolerated in patients with CNSL. These combined therapies offer a new potential therapeutic strategy for patients with CNSL.

Measuring the tuning curve of spontaneous parameter downconversion using a comet-tail-like pattern.

Comet-tail-like interference patterns are observed using photons from the spontaneous parametric downconversion (SPDC) process. The patterns are caused by the angular-spectrum-dependent interference and the diffraction of a blazed grating. We present a theoretical explanation and simulation results for these patterns, which are in good agreement with the experimental results. The most significant feature of the patterns is the bright parabolic contour profile, from which one can deduce the parameter of the parabolic tuning curve of the SPDC process. This method could be helpful when designing experiments based on SPDC.

Facile preparation of a MXene-graphene oxide membrane and its voltage-gated ion transport behavior.

Two-dimensional MXenes have become a crucial topic in the field of ion transportation owing to their excellent electrochemical performance. Herein, a strategy for preparing a layered MXene-graphene oxide (GO) membrane via vacuum filtration is proposed, which endows the delaminated two-dimensional MXene-GO membrane (MGOm) with excellent electrical conductivity and chemical stability, achieving an excellent voltage-gated ion transport behavior. Owing to the presence of charges or dipoles within the membrane's channel, the movement of electrons or dipoles under the influence of membrane potential is possible. By varying the transmembrane potential, the transition between the closed and open states of the voltage-gated ion channel can be adjusted. When a negative potential is applied at osmotic pressure, the force between the charged MGOm sheet and the cation (K+) is enhanced, promoting ion permeation. Conversely, the application of positive potential attenuates electrostatic attraction, resulting in a decrease in ion permeability. In addition, the effects of MXene and GO with different modulation ratios on the voltage-gated ion transport have shown that when the modulation ratio of MXene : GO is 7 : 3, the optimal ion permeation rate is achieved. In conclusion, the conductive film with voltage-gated nanochannels is a promising alternative for ion transportation, opening up new avenues for the further exploration of MXene materials in energy storage devices.

Enhanced ion transport in nanochannels of MXenes by Mg2+ pre-intercalation.

How to enhance the ion transport between MXene layers is a critical topic in the fields of electrochemical storage (especially supercapacitors) and water treatment. Vertical structure design of MXene nanosheets and single-molecule organic pre-intercalation are proposed, but the methods to enhance the ion transport through MXene nanochannels by modulating MXene's surface state have not been investigated yet. The interaction mechanism between Mg2+ and MXene 2D nanochannels during the transport process has not been thoroughly explored. In our work, we used a facile infiltration method to immerse the Ti3C2Tx membranes in MgCl2 solution for ion pre-intercalation. We found that the pre-intercalation of Mg2+ has a significant effect on the increase of the ion transport rate of Ti3C2Tx membranes, especially for Li+ which reached 268.49% compared with those of non-intercalation membranes. Through multiple characterization methods, we discovered that the enhancement of ion transport rate by pre-intercalation of Mg2+ mainly originated from the fact that the pre-intercalation of Mg2+ increased the layer spacing of MXene films as the channel support between layers while Mg2+ increased the work function (WF) of 2D nanochannels thereby reducing the interaction of other ions with the channel surface. The acceleration phenomenon of ion transport by surface state modulation proposed in our work will provide new strategies for the design of structure and regulation of surface states, revealing the mechanism of capacity improvement.

A structural equation modeling approach to determine the correlation between the vertical and sagittal skeletal patterns and posterior basal bones mismatching in patients with skeletal Class III malocclusion.

INTRODUCTION: Matching the maxillomandibular basal bone width is essential to the stability of orthodontic treatment. We aimed to determine the relationship between basal bone width mismatching and the vertical and sagittal skeletal pattern in patients with skeletal Class III malocclusion through shape analysis and structural equation modeling (SEM). METHODS: Cone-beam computed tomography images were collected from 45 men and 51 women. Width mismatching of the basal bone was determined using generalized Procrustes analysis. Twenty-two parameters from the synthesized cephalogram were measured, followed by factor analysis and SEM. RESULTS: Mismatch occurred at the second molar (men, -4.29 ± 4.32 mm; women, -5.55 ± 4.43 mm) and retromolar regions (men, -8.49 ± 5.11 mm; women: -8.93 ± 5.25 mm). The sum of angles had the largest loading for vertical-1 (extracted from 18 vertical cephalometric measurements) (men, 0.9477; women, 0.9489), followed by MP-SN angle (0.9408) in men and N-Me/S-Go (0.9342) in women. Wits appraisal and anteroposterior dysplasia indicator were largest for Sagittal-1. SEM showed a positive effect of male vertical-1 and 2 on width difference in the retromolar region (P <0.001; B >0). Female vertical-1 had a significant positive effect on DW7 (P <0.001; B = 5.535) and DWR (P = 0.016; B = 3.427) as vertical-2. Sagittal-1 showed a negative correlation with DW7 in both genders (P <0.05; B <0) and with DWR in men. CONCLUSIONS: Basal bone width mismatching occurred at the second molar and retromolar regions, especially in low-angle and patients with severe skeletal Class III malocclusion.

Radiotherapy vs sequential pegaspargase, gemcitabine, cisplatin and dexamethasone and radiotherapy in newly diagnosed early natural killer/T-cell lymphoma: A randomized, controlled, open-label, multicenter study.

To compare the efficacy and safety of radiotherapy (RT) and chemotherapy of pegaspargase, gemcitabine, cisplatin and dexamethasone (DDGP) combined with RT in newly diagnosed stage I-II natural killer/T-cell lymphoma (NKTL), we designed a randomized, controlled, open-label, multicenter clinical trial. Data from 65 stage I-II NKTL patients whose diagnoses were confirmed using immunohistochemistry were enrolled from January 2011 to December 2013 in the First Affiliated Hospital of Zhengzhou University. Patients were randomly divided into the RT group (n = 35) and the DDGP combined with RT group (n = 30). There was a difference between the Eastern Cooperative Oncology Group (ECOG) score in the two arms (P = .013). The complete response rate (CRR) and objective response rate (ORR) of DDGP combined with RT group were superior to those in the RT group (CRR: 73.3% vs 48.6%; ORR: 83.3% vs 60.0%, respectively). The 5-year progression-free survival (PFS) rate and overall survival (OS) rate in the DDGP combined with RT group were higher than those in the RT group (82.9% vs 56.5% for PFS, P = .023; 85.7% vs 60.4% for OS, P = .040), and treatment methods and lactate dehydrogenase were independent risk factors. Myelosuppression (P < .001), gastrointestinal reactions (P < .001), abnormal liver function (P = .007), coagulation abnormalities (P < .001) and baldness (P < .001) were more likely to occur in the DDGP combined with RT group. In conclusion, DDGP combined with radiotherapy obviously obtained great efficacy and prolonged the survival time of patients, also the side effects were mild for stage I-II NKTL. This trial was registered at https://register.clinicaltrials.gov as #NCT01501136.

Interference fringes in a nonlinear Michelson interferometer based on spontaneous parametric down-conversion.

Quantum nonlinear interferometers (QNIs) can measure the infrared physical quantities of a sample by detecting visible photons. A QNI with Michelson geometry based on the spontaneous parametric down-conversion in a second-order nonlinear crystal is studied systematically. A simplified theoretical model of the QNI is presented. The interference visibility, coherence length, equal-inclination interference, and equal-thickness interference for the QNI are demonstrated theoretically and experimentally. As an application example of the QNI, the refractive index and the angle between two surfaces of a BBO crystal are measured using equal-inclination interference and equal-thickness interference.

Fourth-harmonic generation of orbital angular momentum light with cascaded quasi-phase matching crystals.

Orbital angular momentum (OAM) light, combined with the nonlinear process to expand the frequency range, has drawn increasing research interest in recent years. Here, we implement the first, to the best of our knowledge, experimental fourth-harmonic generation of OAM light with two cascaded quasi-phase-matching crystals. A Laguerre-Gaussian beam was transmitted through a duplet crystals system and frequency-doubled twice by two separate second-harmonic generation processes, which transduced the frequency of the OAM beam from telecom band to visible band and then to ultraviolet (UV) band. The topological charge of the OAM beam was increased substantially in the cascaded frequency conversion processes. In this experiment, we verify the OAM conservation by utilizing a specially designed interferometer, and the results correspond well with the numerical simulation. This work provides an effective method for the generation of UV OAM beams with high topological charges.

Ibrutinib combined with venetoclax for the treatment of relapsed/refractory diffuse large B cell lymphoma.

Treatment outcomes of relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) are far from satisfactory. Certain efficacy of ibrutinib has been observed in non-GCB subtype DLBCL patients. This study aimed to investigate the efficacy and safety of ibrutinib plus BCL2 inhibitor venetoclax in R/R DLBCL patients with non-GCB subtype and BCL2 overexpression. Combinational therapy (ibrutinib 560mg/day; venetoclax started 1 week later, oral dose increased from 100 to 400mg/day in 3 weeks) was conducted, and one cycle was 4 weeks. Both drugs were stopped when disease progress or serious adverse reactions appear. The primary end-point was overall response rate (ORR) at two cycles. From December 2018 to July 2020, a total of 13 patients were treated with the combined therapy. Among them, eleven (84.6%) patients previously received at least two treatment regimens, eight (61.5%) patients were C-myc and BCL2 double expression. The ORR at two cycles was 61.5%, with 3 (23.1%) patients achieved complete remission (CR) and 5 (38.4%) patients achieved partial remission (PR). The ORR at four cycles and six cycles was 53.8% and 46.2%, respectively. The median duration of response was 11 months (range, 1.5-13.6 months). The median progression-free survival and overall survival were 5.6 months (range, 0.4-15.6) and 11.3 months (range, 2.8-17.2), respectively. The most common adverse event was grade 1/2 neutropenia (53.8%), and nonhematologic toxicities included Grade1/2 diarrhea (46.2%) and elevated liver enzymes (30.8%). Combined therapy of ibrutinib and venetoclax showed promising efficacy and synergistic effects in R/R DLBCL patients with non-GCB subtype and BCL2 overexpression, and the toxicities were well-tolerated.

Sustained zinc release in cooperation with CaP scaffold promoted bone regeneration via directing stem cell fate and triggering a pro-healing immune stimuli.

Metal ions have been identified as important bone metabolism regulators and widely used in the field of bone tissue engineering, however their exact role during bone regeneration remains unclear. Herein, the aim of study was to comprehensively explore the interactions between osteoinductive and osteo-immunomodulatory properties of these metal ions. In particular, the osteoinductive role of zinc ions (Zn2+), as well as its interactions with local immune microenvironment during bone healing process, was investigated in this study using a sustained Zn2+ delivery system incorporating Zn2+ into ß-tricalcium phosphate/poly(L-lactic acid) (TCP/PLLA) scaffolds. The presence of Zn2+ largely enhanced osteogenic differentiation of periosteum-derived progenitor cells (PDPCs), which was coincident with increased transition from M1 to M2 macrophages (M[Formula: see text]s). We further confirmed that induction of M2 polarization by Zn2+ was realized via PI3K/Akt/mTOR pathway, whereas marker molecules on this pathway were strictly regulated by the addition of Zn2+. Synergically, this favorable immunomodulatory effect of Zn2+ further improved the osteogenic differentiation of PDPCs induced by Zn2+ in vitro. Consistently, the spontaneous osteogenesis and pro-healing osteoimmunomodulation of the scaffolds were thoroughly identified in vivo using a rat air pouch model and a calvarial critical-size defect model. Taken together, Zn2+-releasing bioactive ceramics could be ideal scaffolds in bone tissue engineering due to their reciprocal interactions between osteoinductive and immunomodulatory characteristics. Clarification of this synergic role of Zn2+ during osteogenesis could pave the way to develop more sophisticated metal-ion based orthopedic therapeutic strategies.

A second RNA-binding protein is essential for ethanol tolerance provided by the bacterial OLE ribonucleoprotein complex.

OLE (ornate, large, extremophilic) RNAs comprise a class of structured noncoding RNAs (ncRNAs) found in many extremophilic bacteria species. OLE RNAs constitute one of the longest and most widespread bacterial ncRNA classes whose major biochemical function remains unknown. In the Gram-positive alkaliphile Bacillus halodurans, OLE RNA is abundant, and localizes to the cell membrane by association with the transmembrane OLE-associated protein called OapA (formerly OAP). These characteristics, along with the well-conserved sequence and structural features of OLE RNAs, suggest that the OLE ribonucleoprotein (RNP) complex performs important biological functions. B. halodurans strains lacking OLE RNA (∆ole) or OapA (∆oapA) are less tolerant of cold (20 °C) and short-chain alcohols (e.g., ethanol). Here, we describe the effects of a mutant OapA (called PM1) that more strongly inhibits growth under cold or ethanol stress compared with strains lacking the oapA gene, even when wild-type OapA is present. This dominant-negative effect of PM1 is reversed by mutations that render OLE RNA nonfunctional. This finding demonstrates that the deleterious PM1 phenotype requires an intact RNP complex, and suggests that the complex has one or more additional undiscovered components. A genetic screen uncovered PM1 phenotype suppressor mutations in the ybzG gene, which codes for a putative RNA-binding protein of unknown biological function. We observe that YbzG protein (also called OapB) selectively binds OLE RNA in vitro, whereas a mutant version of the protein is not observed to bind OLE RNA. Thus, YbzG/OapB is an important component of the functional OLE RNP complex in B. halodurans.

Real-time quantum edge enhanced imaging.

With the development of optical information processing technology, image edge enhancement technology has rapidly received extensive attention, especially in the field of quantum imaging. However, quantum edge enhanced imaging faces challenges in terms of time-consuming acquisition processes and the complexity of the devices used, which limits practical applications in real-time usage scenarios. Here we introduce and experimentally demonstrate a real-time (0.5 Hz) quantum edge enhanced imaging method that combines the spiral phase contrast technique with heralded single-photon imaging. The edge enhancement results show high quality and background free from raw data. Compared with direct imaging, our configuration can improve the signal-to-noise ratio significantly using the tight time correlations between photon pairs. The method also offers competitive advantages over ghost imaging, including higher brightness and a compact optical fiber delay rather than a free space delay. Additionally, we explore curved edge enhancement for specific feature recognition and the oriented shadow effect. Overall, this efficient and versatile platform paves an alternative path toward real-time quantum edge detection in applications including nondestructive bio-imaging, night vision and covert monitoring.

High-quality versatile photonic sources for multiple quantum optical experiments.

Entangled sources are important components for quantum information science and technology (QIST). The ability to generate high-quality entangled sources will determine the extent of progress in this field. Unlike previous schemes, a thin quasi-phase matching nonlinear crystal and a dense-wave-division-multiplexing device are used here to build high-quality versatile photonic sources with a simple configuration that can be used to perform Hong-Ou-Mandel interference, time-energy entanglement and multi-channel polarization entanglement experiments. The measurement results from various quantum optical experiments show the high quality of these photonic sources. These multi-functional photonic sources will be very useful in a variety of QIST applications.

Complete Blood Count Score Model Integrating Reduced Lymphocyte-Monocyte Ratio, Elevated Neutrophil-Lymphocyte Ratio, and Elevated Platelet-Lymphocyte Ratio Predicts Inferior Clinical Outcomes in Adult T-Lymphoblastic Lymphoma.

BACKGROUND: T-lymphoblastic lymphoma (T-LBL) is a highly aggressive neoplasm of lymphoblasts of T-cell origin. Although promising improvements have been recently achieved, one third of patients experience relapse or refractory T-LBL. Therefore, optimal strategies for identifying high-risk patients are urgently needed. MATERIALS AND METHODS: In the present study, 75 newly diagnosed adult patients (aged ≥15 years) with T-LBL were identified and the predictive value of complete blood count (CBC) abnormalities, including lymphocyte-monocyte ratio (LMR), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) on clinical outcomes, was analyzed. RESULTS: Using the receiver operating characteristic curve to determine the best cutoff values based on survival, it was found that patients with T-LBL with LMR ≤2.8, NLR ≥3.3, and PLR ≥200 had both inferior progression-free survival (PFS) and inferior overall survival (OS), in which the differences were much more remarkable in the international prognostic index score 0-2 subgroup. In the multivariable analysis, NLR ≥3.3 together with age >40 years and central nervous system (CNS) involvement were identified to be independently associated with shortened PFS, whereas PLR ≥200 and CNS involvement were identified to be independent risk factors for OS. LMR, NLR, and PLR were integrated to generate a "CBC score" model, which well separated adult patients with T-LBL into three risk groups, and the 3-year OS was 84%, 53%, and 30% for low-, intermediate-, and high-risk patients, respectively. CONCLUSION: Overall, a "CBC score" model was initially promoted for stratification in adult patients with T-LBL using simple, widely available, and easy to interpret parameters in the largest adult T-LBL cohort to date. IMPLICATIONS FOR PRACTICE: Optimal strategies for identifying high-risk patients with T-lymphoblastic lymphoma (T-LBL) are urgently needed. In the largest adult T-LBL cohort to date, simple, inexpensive, widely available parameters were applied and revealed that patients with lymphocyte-monocyte ratio (LMR) ≤2.8, neutrophil-lymphocyte ratio (NLR) ≥3.3, and platelet-lymphocyte ratio (PLR) ≥200 had both inferior progression-free survival and inferior overall survival (OS), in which the differences were much more remarkable in the international prognostic index score 0-2 subgroup. LMR, NLR, and PLR were integrated to generate a "complete blood count score" model, in which the 3-year OS was 84%, 53%, and 30% for low-, intermediate-, and high-risk patients, respectively.

Classical simulation of high-dimensional entanglement by non-separable angular-radial modes.

An analogous model system for high-dimensional quantum entanglement is proposed, based on the angular and radial degrees of freedom of the improved Laguerre Gaussian mode. Experimentally, we observed strong violations of the Bell-CGLMP inequality for maximally non-separable states of dimension 2 through 10. The results for violations in classical non-separable state are in very good agreement with quantum instance, which illustrates that our scheme can be a useful platform to simulate high-dimensional non-local entanglement. Additionally, we found that the Bell measurements provide sufficient criteria for identifying mode separability in a high-dimensional space. Similar to the two-dimensional spin-orbit non-separable state, the proposed high-dimensional angular-radial non-separable state may provide promising applications for classical and quantum information processing.