New genetic insights into immunotherapy outcomes in gastric cancer via single-cell RNA sequencing and random forest model.

OBJECTIVE: The high mortality rate of gastric cancer, traditionally managed through surgery, underscores the urgent need for advanced therapeutic strategies. Despite advancements in treatment modalities, outcomes remain suboptimal, necessitating the identification of novel biomarkers to predict sensitivity to immunotherapy. This study focuses on utilizing single-cell sequencing for gene identification and developing a random forest model to predict immunotherapy sensitivity in gastric cancer patients. METHODS: Differentially expressed genes were identified using single-cell RNA sequencing (scRNA-seq) and gene set enrichment analysis (GESA). A random forest model was constructed based on these genes, and its effectiveness was validated through prognostic analysis. Further, analyses of immune cell infiltration, immune checkpoints, and the random forest model provided deeper insights. RESULTS: High METTL1 expression was found to correlate with improved survival rates in gastric cancer patients (P = 0.042), and the random forest model, based on METTL1 and associated prognostic genes, achieved a significant predictive performance (AUC = 0.863). It showed associations with various immune cell types and negative correlations with CTLA4 and PDCD1 immune checkpoints. Experiments in vitro and in vivo demonstrated that METTL1 enhances gastric cancer cell activity by suppressing T cell proliferation and upregulating CTLA4 and PDCD1. CONCLUSION: The random forest model, based on scRNA-seq, shows high predictive value for survival and immunotherapy sensitivity in gastric cancer patients. This study underscores the potential of METTL1 as a biomarker in enhancing the efficacy of gastric cancer immunotherapy.

Generation of true quantum random numbers with on-demand probability distributions via single-photon quantum walks.

Random numbers are at the heart of diverse fields, ranging from simulations of stochastic processes to classical and quantum cryptography. The requirement for true randomness in these applications has motivated various proposals for generating random numbers based on the inherent randomness of quantum systems. The generation of true random numbers with arbitrarily defined probability distributions is highly desirable for applications, but it is very challenging. Here we show that single-photon quantum walks can generate multi-bit random numbers with on-demand probability distributions, when the required "coin" parameters are found with the gradient descent (GD) algorithm. Our theoretical and experimental results exhibit high fidelity for various selected distributions. This GD-enhanced single-photon system provides a convenient way for building flexible and reliable quantum random number generators. Multi-bit random numbers are a necessary resource for high-dimensional quantum key distribution.

Quantum ghost imaging of a vector field.

Quantum ghost image technique utilizing position or momentum correlations between entangled photons can realize nonlocal reconstruction of the image of an object. In this work, based on polarization entanglement, we experimentally demonstrate quantum ghost imaging of vector images by using a geometric phase object. We also provide a corresponding theoretical analysis. Additionally, we offer a geometrical optics path explanation of ghost imaging for vector fields. The proposed strategy offers new insights into the fundamental development of ghost imaging and also holds great promise for developing complex structured ghost imaging techniques. Our work expanding the principle of ghost imaging to spatially varying vector beams will lead to interesting developments of this field.

Fast-growing cyanobacterial chassis for synthetic biology application.

Carbon neutrality by 2050 has become one of the most urgent challenges the world faces today. To address the issue, it is necessary to develop and promote new technologies related with CO2 recycling. Cyanobacteria are the only prokaryotes performing oxygenic photosynthesis, capable of fixing CO2 into biomass under sunlight and serving as one of the most important primary producers on earth. Notably, recent progress on synthetic biology has led to utilizing model cyanobacteria such as Synechocystis sp. PCC 6803 and Synechococcus elongatus PCC 7942 as chassis for "light-driven autotrophic cell factories" to produce several dozens of biofuels and various fine chemicals directly from CO2. However, due to the slow growth rate and low biomass accumulation in the current chassis, the productivity for most products is still lower than the threshold necessary for large-scale commercial application, raising the importance of developing high-efficiency cyanobacterial chassis with fast growth and/or higher biomass accumulation capabilities. In this article, we critically reviewed recent progresses on identification, systems biology analysis, and engineering of fast-growing cyanobacterial chassis. Specifically, fast-growing cyanobacteria identified in recent years, such as S. elongatus UTEX 2973, S. elongatus PCC 11801, S. elongatus PCC 11802 and Synechococcus sp. PCC 11901 was comparatively analyzed. In addition, the progresses on their recent application in converting CO2 into chemicals, and genetic toolboxes developed for these new cyanobacterial chassis were discussed. Finally, the article provides insights into future challenges and perspectives on the synthetic biology application of cyanobacterial chassis.

Research Progress on Router Devices for the OAM Optical Communication.

Vortex beams carrying orbital angular momentum (OAM) provide a new degree of freedom for light waves in addition to the traditional degrees of freedom, such as intensity, phase, frequency, time, and polarization. Due to the theoretically unlimited orthogonal states, the physical dimension of OAM is capable of addressing the problem of low information capacity. With the advancement of the OAM optical communication technology, OAM router devices (OAM-RDs) have played a key role in significantly improving the flexibility and practicability of communication systems. In this review, major breakthroughs in the OAM-RDs are summarized, and the latest technological standing is examined. Additionally, a detailed account of the recent works published on techniques related to the OAM-RDs has been categorized into five areas: channel multicasting, channel switching, channel filtering, channel hopping, and channel adding/extracting. Meanwhile, the principles, research methods, advantages, and disadvantages are discussed and summarized in depth while analyzing the future development trends and prospects of the OAM-RDs.

Vision transformers motivating superior OAM mode recognition in optical communications.

Orbital angular momentum (OAM) has recently obtained tremendous research interest in free-space optical communications (FSO). During signal transmission within the free-space link, atmospheric turbulence (AT) poses a significant challenge as it diminishes the signal strength and introduce intermodal crosstalk, significantly reducing OAM mode detection accuracy. This issue directly impacts the performance of OAM-based communication systems and leads to a reduction in received information. To address this critical bottleneck of low mode recognition accuracy in OAM-based FSO-communications, a deep learning method based on vision transformers (ViT) is proposed for what we believe is for the first time. Designed carefully by numerous experts, the advanced self-attention mechanism of ViT captures more global information from the input image. To train the model, pretraining on a large dataset, named IMAGENET is conducted. Subsequently, we performed fine-tuning on our specific dataset, consisting of OAM beams that have undergone varying AT strengths. The computer simulation shows that based on ViT method, the multiple OAM modes can be recognized with a high accuracy (nearly 100%) under weak-to-moderate turbulence and with almost 98% accuracy even under long transmission distance with strong turbulence (C N2=1×10-14). Our findings highlight that leveraging ViT enables robust detection of complex OAM beams, mitigating the adverse effects caused by atmospheric turbulence.

Generating an M2 × N2 spot array with a dual-period hybrid Dammann grating fabricated using maskless projection lithography.

The Dammann grating (DG), which redistributes a collimated laser beam into a spot array with a uniform intensity, is a widely adopted approach for profile measurement. Conventional DGs for dense spot projection are binary phase gratings with precisely designed groove structures, which suffer from low efficiency, poor uniformity, and a hard-to-fabricate fine feature size when utilized for a large field of view (FOV). Here, we propose a new, to the best of our knowledge, hybrid DG architecture consisting of two different grating periods which effectively generates an engineering M2 × N2 spot array with a non-complex structural design. As a proof-of-concept, a dual-period hybrid DG with a two-scale grating period ratio of 11.88 µm/95.04 µm (∼1/8) is designed and fabricated as a means to generate a dense 72 × 72 diffraction spot array with a FOV of 17° × 17°. In addition, the DG exhibits superior performance, with a high efficiency (>60%) and a low non-uniformity (<18%) at a wavelength of 532 nm. This kind of hybrid DG constructed from photoresist patterns with a minimum feature size of ∼1.2 µm can be perfectly fabricated by maskless projection lithography for large-scale and low-cost production. The proposed dual-period hybrid DG can pave the way for depth-perception-related applications such as face unlocking and motion sensing.

From materials to clinical use: advances in 3D-printed scaffolds for cartilage tissue engineering.

Osteoarthritis caused by articular cartilage defects is a particularly common orthopedic disease that can involve the entire joint, causing great pain to its sufferers. A global patient population of approximately 250 million people has an increasing demand for new therapies with excellent results, and tissue engineering scaffolds have been proposed as a potential strategy for the repair and reconstruction of cartilage defects. The precise control and high flexibility of 3D printing provide a platform for subversive innovation. In this perspective, cartilage tissue engineering (CTE) scaffolds manufactured using different biomaterials are summarized from the perspective of 3D printing strategies, the bionic structure strategies and special functional designs are classified and discussed, and the advantages and limitations of these CTE scaffold preparation strategies are analyzed in detail. Finally, the application prospect and challenges of 3D printed CTE scaffolds are discussed, providing enlightening insights for their current research.

Electronic Configuration Tuning of Centrally Extended Non-Fullerene Acceptors Enabling Organic Solar Cells with Efficiency Approaching 19 .

In the molecular optimizations of non-fullerene acceptors (NFAs), extending the central core can tune the energy levels, reduce nonradiative energy loss, enhance the intramolecular (donor-acceptor and acceptor-acceptor) packing, facilitate the charge transport, and improve device performance. In this study, a new strategy was employed to synthesize acceptors featuring conjugation-extended electron-deficient cores. Among these, the acceptor CH-BBQ, embedded with benzobisthiadiazole, exhibited an optimal fibrillar network morphology, enhanced crystallinity, and improved charge generation/transport in blend films, leading to a power conversion efficiency of 18.94 % for CH-BBQ-based ternary organic solar cells (OSCs; 18.19 % for binary OSCs) owing to its delicate structure design and electronic configuration tuning. Both experimental and theoretical approaches were used to systematically investigate the influence of the central electron-deficient core on the properties of the acceptor and device performance. The electron-deficient core modulation paves a new pathway in the molecular engineering of NFAs, propelling relevant research forward.

All-Small-Molecule Organic Solar Cells with Efficiency Approaching 16% and FF over 80.

Molecule engineering has been demonstrated as a valid strategy to adjust the active layer morphology in all-small-molecule organic solar cells (ASM-OSCs). In this work, two non-fullerene acceptors (NFAs), FO-2Cl and FO-EH-2Cl, with different alkyl side chains are reported and applied in ASC-OSCs. Compared with FO-2Cl, FO-EH-2Cl is designed by replacing the octyl alkyl chains with branched iso-octyl alkyl chains, leading to an enhanced molecular packing, crystallinity, and redshifted absorption. With a small molecule BSFTR as donor, the device of BSFTR:FO-EH-2Cl obtains a better morphology and achieves a higher power conversion efficiency (PCE) of 15.78% with a notable fill factor (FF) of 80.44% than that of the FO-2Cl-based device with a PCE of 15.27% and FF of 78.41%. To the authors' knowledge, the FF of 80.44% is the highest value in ASM-OSCs. These results demonstrate a good example of fine-tuning the molecular structure to achieve suitable active layer morphology with promising performance for ASM-OSCs, which can provide valuable insight into material design for high-efficiency ASM-OSCs.

Ultralow-power all-optical switching via a chiral Mach-Zehnder interferometer.

It is a challenge for all-optical switching to simultaneous achieve ultralow power consumption, broad bandwidth and high extinction ratio. We experimentally demonstrate an ultralow-power all-optical switching by exploiting chiral interaction between light and optically active material in a Mach-Zehnder interferometer. We achieve switching extinction ratio of 20.0 ± 3.8 and 14.7 ± 2.8 dB with power cost of 66.1 ± 0.7 and 1.3 ± 0.1 fJ/bit, respectively. The bandwidth of our all-optical switching is about 4.2 GHz. Moreover, our all-optical switching has the potential to be operated at few-photon level. Our scheme paves the way towards ultralow-power and ultrafast all-optical information processing.

Central Unit Fluorination of Non-Fullerene Acceptors Enables Highly Efficient Organic Solar Cells with Over 18 % Efficiency.

Halogenation of terminal of acceptors has been shown to give dramatic improvements in power conversion efficiencies (PCEs) of organic solar cells (OSCs). Similar significant results could be expected from the halogenation of the central units of state-of-the-art Y-series acceptors. Herein, a pair of acceptors, termed CH6 and CH4, featuring a conjugation-extended phenazine central unit with and without fluorination, have been synthesized. The fluorinated CH6 has enhanced molecular interactions and crystallinity, superior fibrillar network morphology and improved charge generation and transport in blend films, thus affording a higher PCE of 18.33 % for CH6-based binary OSCs compared to 16.49 % for the non-fluorinated CH4. The new central site offers further opportunities for structural optimization of Y-series molecules to afford better-performed OSCs and reveals the effectiveness of fluorination on central units.

MiR-449a Sponges Cyclin D1 Expression and Suppresses Phosphorylation of Retinoblastoma Protein against Osteosarcoma.

MiR-449a has tumor-regulatory properties in different cancers, but its role in osteosarcoma had not been clearly understood. This research aimed to study the underlying mechanism of how miR-449a regulates osteosarcoma cells. The expression of miR-449a, cyclin D1, and pRb in osteosarcoma tissues and cultivated cells was assessed by qRT-PCR, western blot, and immunofluorescent assay. Dual-luciferase reporter assay was conducted to verify the target of miR-449a. Western blot, CCK-8, colony formation, and flow cytometry assays were applied to examine the regulatory effects of miR-449a on osteosarcoma cells and the molecular mechanism. MiR-449a and pRb expression was impeded whereas cyclin D1 expression was enhanced in osteosarcoma tissues and cells. Cyclin D1 was confirmed as a target of miR-449a. MiR-449a impeded the viability and proliferation of osteosarcoma cells and controlled the cell cycle through targeting cyclin D1 to reduce pRB phosphorylation. These findings provided evidence that miR-449a played an anticancer role in osteosarcoma cells by directly targeting cyclin D1 to prevent pRb from phosphorylation. Our study suggested that miR-449a might have the potential to become a new therapeutic biomarker involved in the diagnosis, prevention, and treatment of osteosarcoma.

Upconversion Luminescence-Controlled DNA Computation for Spatiotemporally Resolved, Multiplexed Molecular Imaging.

DNA-based molecular circuits able to perform complex information processing in biological systems are highly desirable. However, conventional DNA circuits are constitutively always in an ON state and immediately operate when they meet the biomolecular inputs, precluding precise molecular computation at a desired time and in a desired site. In this work, we report a conceptual methodology for the construction of photonic nanocircuits that enable DNA molecular computation in vitro and in vivo with high spatial precision. Upon remote activation by spatially restricted NIR-light input, two types of cancer biomarker inputs can sequentially trigger conformational changes of the DNA circuit through a structure-switching aptamer and toehold-mediated strand exchange, leading to release of a signaling output. Of note, the NIR-light-gated nanocircuit allows for intended control over the specific timing and location of DNA computation, providing spatial and temporal capabilities for multiplexed imaging. Furthermore, an OR-AND-gated nanocircuit of higher complexity was designed to illustrate the versatility of our approach. The present work illustrates the potential of the use of upconversion nanotechnology as a regulatory tool for spatial and temporal control of DNA computation in cells and animals.

Band evolution and Landau-Zener Bloch oscillations in strained photonic rhombic lattices.

We investigate band evolution of chiral and non-chiral symmetric flatband photonic rhombic lattices by applying a strain along the diagonal direction, and thereby demonstrating Landau-Zener Bloch (LZB) oscillations in the presence of a refractive index gradient. The chiral and non-chiral symmetric rhombic lattices are obtained by adding a detuning to uniform lattices. For the chiral symmetric lattices, the middle flatband is perturbed due to the chiral symmetry breaking while a nearly flatband appears as the bottom band with the increase of strain-induced next-nearest-neighbor hopping. Consequently, LZB oscillations exhibit intriguing characteristics such as asymmetric energy transitions and almost complete suppression of the oscillations. Nevertheless, for the non-chiral symmetric lattices, flatband persists owing to the retained particle-hole symmetry and evolves into the bottom band. Remarkably, the band gap can be readily tuned, which allows controlling of the amplitude of Landau-Zener tunneling (LZT) rate and may lead to thorough LZT. Our analysis provides an alternative perspective on the generation of tunable flatband and may also bring insight to study the symmetry and topological characterization of the flatband.

Self-healing of a heralded single-photon Airy beam.

Self-healing of an Airy beam during propagation is of fundamental interest and also promises important applications. Despite many studies of Airy beams in the quantum regime, it is unclear whether an Airy beam only including a single photon can heal after passing an obstacle because the photon may be blocked. Here we experimentally observe self-healing of a heralded single-photon Airy beam. Our observation implies that an Airy wave packet is robust against obstacle caused distortion and can restore even at the single-photon level.

Spatially Selective Imaging of Mitochondrial MicroRNAs via Optically Programmable Strand Displacement Reactions.

MicroRNA (miRNA) functions are tightly regulated by their sub-compartmental location in living cells, and the ability to imaging of mitochondrial miRNAs (mitomiRs) is essential for understanding of the related pathological processes. However, most existing DNA-based methods could not be used for this purpose. Here, we report the development of a DNA nanoreporter technology for imaging of mitomiRs in living cells through near-infrared (NIR) light-controlled DNA strand displacement reactions. The sensing function of the DNA nanoreporters are silent (OFF) during the delivery process, but can be photoactivated (ON) with NIR light after targeted mitochondrial localization, enabling spatially-restricted imaging of two types of cancer-related mitomiRs with improved detection accuracy. Furthermore, we demonstrate imaging of mitomiRs in vivo through spatiotemporally-controlled delivery and activation. Therefore, this study illustrates a simple methodology that may be broadly applicable for investigating the mitomiRs-associated physiological events.

In Vivo Self-Assembly Induced Cell Membrane Phase Separation for Improved Peptide Drug Internalization.

Therapeutic peptides have been widely concerned, but their efficacy is limited by the inability to penetrate cell membranes, which is a key bottleneck in peptide drugs delivery. Herein, an in vivo self-assembly strategy is developed to induce phase separation of cell membrane that improves the peptide drugs internalization. A phosphopeptide KYp is synthesized, containing an anticancer peptide [KLAKLAK]2 (K) and a responsive moiety phosphorylated Y (Yp). After interacting with alkaline phosphatase (ALP), KYp can be dephosphorylated and self-assembles in situ, which induces the aggregation of ALP and the protein-lipid phase separation on cell membrane. Consequently, KYp internalization is 2-fold enhanced compared to non-responsive peptide, and IC50 value of KYp is approximately 5 times lower than that of free peptide. Therefore, the in vivo self-assembly induced phase separation on cell membrane promises a new strategy to improve the drug delivery efficacy in cancer therapy.

Identification of cellular microRNA miR-188-3p with broad-spectrum anti-influenza A virus activity.

BACKGROUND: Influenza A virus (IAV) continues to pose serious threats to public health. The current prophylaxis and therapeutic interventions for IAV requires frequent changes due to the continuous antigenic drift and antigenic shift of IAV. Emerging evidence indicates that the host microRNAs (miRNAs) play critical roles in intricate host-pathogen interaction networks. Cellular miRNAs may directly target virus to inhibit its infection and be developed as potential anti-virus drugs. METHODS: In this study, we established a broad-spectrum anti-IAV miRNA screening method using miRanda software. The screened miRNAs were further verified by luciferase assay, viral protein expression assay and virus replication assay. RESULTS: Five cellular miRNAs (miR-188-3p, miR-345-5p, miR-3183, miR-15-3p and miR-769-3p), targeting 99.96, 95.31, 92.9, 94.58 and 97.24% of human IAV strains recorded in NCBI, respectively, were chosen for further experimental verification. Finally, we found that miR-188-3p downregulated PB2 expression at both mRNA and protein levels by directly targeted the predicted sites on PB2 and effectively inhibited the replication of IAV (H1N1, H5N6 and H7N9) in A549 cells. CONCLUSIONS: This is the first report screening cellular miRNAs that broad-spectrum inhibiting IAV infection. These findings suggested that cellular miR-188-3p could be used for RNAi-mediated anti-IAV therapeutic strategies.

Regional metastasis to anatomies beyond traditional neck dissection boundaries: a multi-institutional analysis focused on unconventional metastases in oral cancer patients.

BACKGROUND: Regional metastasis sometimes occurs in anatomies that are not included in traditional neck dissections. The purpose of this study was to evaluate the treatment outcomes of squamous cell carcinoma of oral cavity (SCCOC) patients with unconventional metastatic lymph nodes (UMLNs) in sublingual, buccinator, and parotid anatomies. METHODS: This retrospective multi-institutional analysis of squamous cell carcinoma of oral cavity patients with unconventional metastatic lymph nodes was performed from January 2008 to December 2015. All the included patients received surgical treatment for unconventional metastatic lymph nodes. The end point of the study was to determine the factors influencing these patients' survival and the corresponding solutions to improve survival. Pathological grade, contralateral metastasis, extranodal extension, and other factors were collected and analyzed by logistic regression and the Cox model. RESULTS: A total of 89 patients were identified. Among these patients, 25 (28.1%) received primary treatment, 28 (31.5%) received staged (therapeutic) neck dissections, and 36 (40.4%) had recurrent or residual diseases. Altogether, 45 patients (51%) had buccinator node metastases, 31 (35%) had sublingual metastases, 12 (14%) had parotid metastases, and 1 had both buccinator and parotid metastases. Regarding regional metastases, 31 patients (34.8%) had isolated unconventional metastatic lymph nodes. Adjuvant therapies were administered to 72 (80.9%) patients, 25 (28.1%) of whom were treated with radio-chemotherapies. The overall survival rate was 38.2%. Multivariate analysis found that the subsites of unconventional metastatic lymph nodes (P = 0.029), extranodal extension in both unconventional metastatic lymph nodes (P = 0.025) and cervical lymph nodes (P = 0.015), sites of primary or recurrent squamous cell carcinoma of oral cavity (P = 0.035), and types of neck dissections (P = 0.025) were significantly associated with overall survival. CONCLUSIONS: Unconventional metastatic lymph nodes are uncommon, yet awareness of potential unconventional metastatic lymph nodes should be heightened. Early surgical interventions are warranted in patients with sublingual or buccinator metastases, while caution should be given to those with parotid metastases. Aggressive en bloc (in-continuity) resections may be mandatory in advanced oral cancer cases for close anatomic locations with possible buccal or sublingual metastases.