MOICS, a novel classier deciphering immune heterogeneity and aid precise management of clear cell renal cell carcinoma at multiomics level.

Recent studies have indicated that the tumor immune microenvironment plays a pivotal role in the initiation and progression of clear cell renal cell carcinoma (ccRCC). However, the characteristics and heterogeneity of tumor immunity in ccRCC, particularly at the multiomics level, remain poorly understood. We analyzed immune multiomics datasets to perform a consensus cluster analysis and validate the clustering results across multiple internal and external ccRCC datasets; and identified two distinctive immune phenotypes of ccRCC, which we named multiomics immune-based cancer subtype 1 (MOICS1) and subtype 2 (MOICS2). The former, MOICS1, is characterized by an immune-hot phenotype with poor clinical outcomes, marked by significant proliferation of CD4+ and CD8+ T cells, fibroblasts, and high levels of immune inhibitory signatures; the latter, MOICS2, exhibits an immune-cold phenotype with favorable clinical characteristics, characterized by robust immune activity and high infiltration of endothelial cells and immune stimulatory signatures. Besides, a significant negative correlation between immune infiltration and angiogenesis were identified. We further explored the mechanisms underlying these differences, revealing that negatively regulated endopeptidase activity, activated cornification, and neutrophil degranulation may promote an immune-deficient phenotype, whereas enhanced monocyte recruitment could ameliorate this deficiency. Additionally, significant differences were observed in the genomic landscapes between the subtypes: MOICS1 exhibited mutations in TTN, BAP1, SETD2, MTOR, MUC16, CSMD3, and AKAP9, while MOICS2 was characterized by notable alterations in the TGF-ß pathway. Overall, our work demonstrates that multi-immune omics remodeling analysis enhances the understanding of the immune heterogeneity in ccRCC and supports precise patient management.

Disitamab Vedotin Alone or in Combination With Immune Checkpoint Inhibitors in Bladder-Sparing Treatment of Muscle-Invasive Bladder Cancer: A Real-World Study.

PURPOSE: To evaluate the efficacy and safety of a novel humanized anti-HER2 antibody, RC48-ADC (Disitamab vedotin, DV), the combination of RC48-ADC with PD-1 inhibitors was used to treat muscle-invasive bladder cancer (MIBC). This combination therapy has potential applications in both bladder preservation and neoadjuvant therapy for MIBC. METHODS: Patients with MIBC underwent transurethral resection of bladder tumors followed by RC48-ADC alone or in combination with PD-1 inhibitors. Radiological and endoscopic evaluations were conducted 3 months later. The primary endpoint was objective response rate (ORR), with secondary endpoints including complete response rate (CR), partial response rate (PR), and bladder preservation rate. Treatment safety was assessed according to RECIST v1.1 criteria. RESULTS: Eleven patients were enrolled, with a median follow-up of 19.0 months. Nine patients achieved objective response, including 6 CR and 3 PR cases. The pathological ORR was 81.8%. Eight patients continued combined treatment after 3 months, maintaining a 72.7% bladder preservation rate at 16 months. One elderly patient progressed from ypT2N0M0 to ypT3N0M0 and underwent radical cystectomy but had no recurrence or metastasis 12 months postoperation. All patients reported varying degrees of treatment-related adverse reactions, which were largely manageable. CONCLUSION: The combination of RC48-ADC and PD-1 inhibitors proves to be a viable and safe option for bladder-sparing therapy, particularly for T2-stage MIBC patients who are ineligible for surgery and chemotherapy. This approach offers a promising new direction for bladder preservation or neoadjuvant therapy in MIBC patients.

Wireless-Channel Key Distribution Based on Laser Synchronization.

We propose and experimentally demonstrate a wireless-channel key distribution scheme based on laser synchronization induced by a common wireless random signal. Two semiconductor lasers are synchronized under injection of the drive signal after electrical-optical conversion and emit irregular outputs that are used to generate shared keys. Our proof-of-concept experiment using a complex drive signal achieved a secure key generation rate of up to 150 Mbit/s with a bit error rate below 3.8 × 10-3. Numerical simulation results show that the proposed scheme has the potential to achieve a distribution distance of several hundred meters. It is believed that common-signal-induced laser synchronization paves the way for high-speed wireless physical-layer key distribution.

Multiomics-based classifier to decipher immune landscape of uveal melanoma and predict patient outcomes.

Uveal melanoma (UVM) prognosis and the possibilities for targeted therapy depend on a thorough understanding of immune infiltration features and the analysis of genomic and immune signatures. Leveraging multi-omics data from The Cancer Genome Atlas and GEO datasets, we employed an unsupervised clustering algorithm to categorize UVM into immune-related subgroups. Subsequent multi-omics analysis revealed two distinct UVM subtypes, each characterized by unique genomic mutations and immune microenvironment disparities. The aggressive UMCS2 subtype exhibited higher TNM stage and poorer survival, marked by elevated metabolism and increased immune infiltration. However, UMCS2 displayed heightened tumor mutational burden and immune dysfunction, leading to reduced responsiveness to immunotherapy. Importantly, these subtypes demonstrated differential sensitivity to targeted drugs due to significant variances in metabolic and immune environments, with UMCS2 displaying lower sensitivity. We developed a robust, subtype-specific marker-based risk scoring system. This system's diagnostic accuracy was validated through ROC curves, decision curve analysis, and calibration curves, all yielding satisfactory results. Additionally, cell experiments identified the pivotal function of HTR2B, the most crucial factor in this risk model. Knocking down HTR2B significantly reduced the activity, proliferation, and invasion ability of the UVM cell line. These findings underscored the impact of gene and immune microenvironment alterations in driving distinct molecular subtypes, emphasizing the need for precise treatment strategies. The molecular subtyping-based risk assessment system not only aids in predicting patient prognosis but also guides the identification of populations suitable for combined treatment. Molecules represented by HTR2B in the model may serve as effective therapeutic targets for UVM.Communicated by Ramaswamy H. Sarma.

Enhancing cold resistance in Banana (Musa spp.) through EMS-induced mutagenesis, L-Hyp pressure selection: phenotypic alterations, biomass composition, and transcriptomic insights.

BACKGROUND: The cultivation of bananas encounters substantial obstacles, particularly due to the detrimental effects of cold stress on their growth and productivity. A potential remedy that has gained attention is the utilization of ethyl mesylate (EMS)-induced mutagenesis technology, which enables the creation of a genetically varied group of banana mutants. This complex procedure entails subjecting the mutants to further stress screening utilizing L-Hyp in order to identify those exhibiting improved resistance to cold. This study conducted a comprehensive optimization of the screening conditions for EMS mutagenesis and L-Hyp, resulting in the identification of the mutant cm784, which exhibited remarkable cold resistance. Subsequent investigations further elucidated the physiological and transcriptomic responses of cm784 to low-temperature stress. RESULTS: EMS mutagenesis had a substantial effect on banana seedlings, resulting in modifications in shoot and root traits, wherein a majority of seedlings exhibited delayed differentiation and limited elongation. Notably, mutant leaves displayed altered biomass composition, with starch content exhibiting the most pronounced variation. The application of L-Hyp pressure selection aided in the identification of cold-resistant mutants among seedling-lethal phenotypes. The mutant cm784 demonstrated enhanced cold resistance, as evidenced by improved survival rates and reduced symptoms of chilling injury. Physiological analyses demonstrated heightened activities of antioxidant enzymes and increased proline production in cm784 when subjected to cold stress. Transcriptome analysis unveiled 946 genes that were differentially expressed in cm784, with a notable enrichment in categories related to 'Carbohydrate transport and metabolism' and 'Secondary metabolites biosynthesis, transport, and catabolism'. CONCLUSION: The present findings provide insights into the molecular mechanisms that contribute to the heightened cold resistance observed in banana mutants. These mechanisms encompass enhanced carbohydrate metabolism and secondary metabolite biosynthesis, thereby emphasizing the adaptive strategies employed to mitigate the detrimental effects induced by cold stress.

New Quasi-Solid-State Li-SPAN Battery Enhanced by In Situ Thermally Polymerized Gel Polymer Electrolytes.

A lithium-sulfur (Li-S) battery is a promising candidate for an electrochemical energy-storage system. However, for a long time, it suffered from the "shuttle effect" of the intermediate products of soluble polysulfides and safety issues concerning the combustible liquid electrolyte and lithium anode. In this work, sulfide polyacrylonitrile (SPAN) is employed as a solid cycled cathode to resolve the "shuttle effect" fundamentally, a gel polymer electrolyte (GPE) based on poly(ethylene glycol) diacrylate (PEGDA) is matched to the SPAN cathode to minimize the safety concerns, and finally, a quasi-solid-state Li-SPAN battery is combined by an in situ thermal polymerization strategy to improve its adaptability to the existing battery assembly processes. The PEGDA-based GPE achieved at 60 °C for 40 min ensures little damage to the in situ battery, a good electrode-electrolyte interface, a high ionic conductivity of 6.87 × 10-3 S cm-1 at 30 °C, and a wide electrochemical window of 4.53 V. Ultimately, the as-prepared SPAN composite exerts a specific capacity of 1217.3 mAh g-1 after 250 cycles at 0.2 C with a high capacity retention rate of 89.9%. The combination of the SPAN cathode and in situ thermally polymerized PEGDA-based GPE provides a new inspiration for the design of Li-SPAN batteries with both high specific energy and high safety.

Security optimization of synchronization in DFB lasers under constant-amplitude random-phase drive light by reducing drive-response correlation.

Common-signal-induced laser synchronization promoted a promising paradigm of high-speed physical key distribution. Constant-amplitude and random-phase (CARP) light was proposed as the common drive signal to enhance security by reducing the correlation between the drive and the laser response in intensity. However, the correlation in light phase is not examined. Here, we numerically reveal that the correlation coefficient of the CARP light phase and the response laser intensity (denoted as CCR-φD) can reach a value close to 0.6. Effects of parameters including optical frequency detuning, and modulation depth and noise bandwidth and transparency carrier density for CARP light generation are investigated in detail. By optimizing the optical frequency, modulation depth, and noise bandwidth, respectively, CCR-φD can be reduced to 0.32, 0.18, and 0.10. In the meantime, CCR-φD can be further reduced through secondary optimizing of parameters. CCR-φD can be further reduced by increasing transparent carrier density provided response laser synchronization is achieved. This work gives a new insight about the laser synchronization induced by common CARP light, and also contributes a suggestion of security improvement for physical key distribution based on laser synchronization.

High-speed secure key distribution based on interference spectrum-shift keying with signal mutual modulation in commonly driven chaos synchronization.

The secure key generation and distribution (SKGD) are unprecedentedly important for a modern secure communication system. This paper proposes what we believe to be a novel scheme of high-speed key distribution based on interference spectrum-shift keying with signal mutual modulation in commonly driven chaos synchronization. In this scheme, delay line interferometers (DLI) are utilized to generate two low-correlation interference spectra from commonly driven synchronous chaos, and then a 2 × 2 optical switch can effectively change the relationship between the two interference spectra in post-processing by shifting the states of the switch. The signals then undergo electro-optic nonlinear transformation through a hardware module, which includes a signal mutually modulating module (SMMM) and a dispersion component. This optimization significantly enhances the entropy source rate of synchronized chaos from both legitimate users. Moreover, thanks to the introduction of DLIs and electro-optic nonlinear transformation module, the key space of the proposed scheme is remarkably improved. In comparison to traditional chaotic drive-response architectures, the scheme effectively suppresses residual correlation. A 6.7 Gbit/s key distribution rate with a bit error rate below 3.8 × 10-3 is experimentally demonstrated over a 40 km single-mode fiber (SMF).

Chaos synchronization of VCSELs with common injection of polarization-random light.

We propose and numerically demonstrate chaos synchronization of two vertical-cavity surface-emitting lasers (VCSELs) induced by common injection of constant-amplitude random-polarization light for physical key distribution. Results show that synchronization is sensitive to polarization rotation of injection light, and synchronization coefficients larger than 0.9 can be achieved as the rotation-degree mismatch is smaller than ±10°. Therefore, polarization rotation degree can serve as a hardware key parameter. Furthermore, each laser's output has no correlation to the constant amplitude of the injected light. Their components with identical polarization state, e.g. x or y polarization of VCSEL, also have low correlation coefficient smaller than 0.2. It is therefore believed that this synchronization scheme can provide a security-enhanced method of physical key distribution.

Multifunctional Asymmetric Separator Constructed by Polyacrylonitrile-Derived Nanofibers for Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries hold great promise as next-generation high-energy storage devices owing to the high theoretical specific capacity of sulfur, but polysulfide shuttling and lithium dendrite growth remain key challenges limiting cycling life. In this work, we propose a polyacrylonitrile-derived asymmetric (PDA) separator to enhance Li-S battery performance by accelerating sulfur redox kinetics and guiding lithium plating and stripping. A PDA separator was constructed from two layers: the cathode-facing side consists of polyacrylonitrile nanofibers carbonized at 800 °C and doped with titanium nitride, which can achieve rapid polysulfide conversion via electrocatalysis to suppress their shuttling; the anode-facing side consists of polyacrylonitrile oxidized at 280 °C, on which the abundant electronegative groups guide uniform lithium ion plating and stripping. Li-S batteries assembled with the PDA separator exhibited enhanced rate performance, cycling stability, and sulfur utilization, retaining 426 mA h g-1 capacity at 1 C over 1000 cycles and 632 mA h g-1 at 4 C over 200 cycles. Attractively, the PDA separator showed high thermal stability, which could mitigate the risk of internal short circuits and thermal runaway. This work demonstrates an original path to addressing the most critical issues with Li-S batteries.

Photonic reservoir computing with a silica microsphere cavity.

We experimentally demonstrate a photonic reservoir computing (RC) system using a passive silica microsphere cavity. The microsphere cavity exhibits a consistent nonlinear response to the non-return-to-zero signal and the multiple-level signal due to strong interference between numerous whispering gallery modes in the "over-coupling" state. Benefiting from the fact that the long photon lifetime inside the microsphere cavity provides a memory of past inputs, this photonic reservoir does not require a delayed feedback loop. We evaluate the generalization property of the RC system and obtain a correlation coefficient of 0.923. In addition, we obtain a NMSE of 0.06 for the Santa-Fe chaotic time series prediction task and a SER of 0.02 at a SNR of 12 dB for the nonlinear channel equalization task. Moreover, a microsphere cavity with a higher quality factor can provide a larger memory capacity. The application of the silica microsphere cavity as a small-volume passive device in a reservoir furnishes a new avenue for achieving a low-consumption and integrated RC system.

Comprehensive analysis of the prognosis and immune infiltration of TMC family members in renal clear cell carcinoma.

Renal cancer is a common malignancy of the urinary system, and renal clear cell carcinoma (RCCC) is the most common pathological type. Transmembrane channel-like (TMC) protein is an evolutionarily conserved gene family containing 8 members, however there is still a lack of comprehensive analysis about TMC family members in RCCC. In this study, we analyzed the expression of TMC family members in RCCC from TCGA and investigated the prognosis values and immune infiltration of TMC family members in RCCC. We found that TMC2, TMC3, TMC5, TMC7 and TMC8 were significantly related with overall survival (OS) of RCCC patients. TMC3, TMC6, and TMC8 was positively correlated with the degree of immune infiltration in RCCC. TMC2, TMC6, TMC7, and TMC8 were positively correlated with immune checkpoint genes, whereas TMC4 was negative. According to KEGG and GO analysis, almost all TMCs except TMC4 were involved in the immune response. Thus, we may regard the TMC family members as novel biomarkers to predict potential prognosis and immunotherapeutic response in RCCC patients.

Wideband chaos synchronization using discrete-mode semiconductor lasers.

Optical chaos communication encounters difficulty in high-speed transmission due to the challenge of realizing wideband chaos synchronization. Here, we experimentally demonstrate a wideband chaos synchronization using discrete-mode semiconductor lasers (DMLs) in a master-slave open-loop configuration. The DML can generate wideband chaos with a 10-dB bandwidth of 30 GHz under simple external mirror feedback. By injecting the wideband chaos into a slave DML, an injection-locking chaos synchronization with synchronization coefficient of 0.888 is realized. A parameter range with frequency detuning of -18.75 GHz to approximately 1.25 GHz under strong injection is identified for yielding the wideband synchronization. In addition, we find it more susceptible to achieve the wideband synchronization using the slave DML with lower bias current and smaller relaxation oscillation frequency.

High-entropy-rate broadband chaos generation by using short-resonant-cavity DFB semiconductor laser with optical feedback.

Semiconductor lasers with delayed optical feedback are a promising source of optical chaos for practical applications, owing to simple configurations that are easy to integrate and synchronize. However, for traditional semiconductor lasers, the chaos bandwidth is limited by the relaxation frequency to several gigahertz. Here, we propose and experimentally demonstrate that a short-resonant-cavity distributed-feedback (SC-DFB) laser can generate broadband chaos only with simple feedback from an external mirror. The short distributed-feedback resonant cavity not only enhances laser relaxation frequency but also makes the laser mode more susceptible to external feedback. Experiments obtained a laser chaos with 33.6 GHz bandwidth and a spectral flatness of 4.5 dB. The corresponding entropy rate is estimated as more than 33.3 Gbit/s. It is believed that the SC-DFB lasers will promote development of chaos-based secure communication and physical key distribution.

Numerical and experimental investigation of a dispersive optoelectronic oscillator for chaotic time-delay signature suppression.

Chaos generation from a novel single-loop dispersive optoelectronic oscillator (OEO) with a broadband chirped fiber Bragg grating (CFBG) is numerically and experimentally investigated. The CFBG has much broader bandwidth than the chaotic dynamics such that its dispersion effect rather than filtering effect dominates the reflection. The proposed dispersive OEO exhibits chaotic dynamics when sufficient feedback strength is guaranteed. Suppression of chaotic time-delay signature (TDS) is observed as the feedback strength increases. The TDS can be further suppressed as the amount of grating dispersion increases. Without compromising bandwidth performance, our proposed system extends the parameter space of chaos, enhances the robustness to modulator bias variation, and improves TDS suppression by at least five times comparing to the classical OEO. Experimental results qualitatively agree well with numerical simulations. In addition, the advantage of dispersive OEO is further verified by experimentally demonstrating random bit generation with tunable rate up to 160 Gbps.

Performance improvement of coherent optical chaos communication using probabilistic shaping.

We numerically investigate the effects of probabilistic shaping on the performance improvement of coherent optical chaos communication. Results show that the decryption bit-error ratio (BER) of the 16-ary quadrature amplitude modulation (QAM) signal decreases upon increasing the probabilistic shaping factor. It is predicted that the BER of 10-GBd 16QAM can be decreased by one order of magnitude. On the other hand, for the forward error correction threshold of the BER, the requirement for synchronization quality is no longer strict for successful decryption. This means that probabilistic shaping improves the system's tolerance to residual synchronization error. Thus, the transmission rate can be increased by approximately 30∼60%. The side effect of probabilistic shaping is that the valid masking coefficient range is narrowed.

Deciphering the Role of Melatonin-Related Signatures in Tumor Immunity and the Prognosis of Clear Cell Renal Cell Carcinoma.

Methods: Adopting multiomics data from TCGA and other public datasets, we analysed the expression, mutation, and prognostic evaluation in multiple cancers. ccRCC patients were categorized into two subgroups by an unsupervised cluster algorithm: melatonin-pattern cancer subtype 1 (MPCS1) and subtype 2 (MPCS2). We then explored the immune microenvironment, immune therapy response, and tumor metabolic pathways between the two subtypes. The clinical characteristics, genomic mutation landscape, and molecular inhibitor response were further investigated. Finally, a melatonin regulator-related prognostic model was constructed to predict patient prognosis in ccRCC. Results: We found that melatonin regulators were dysregulated depending on distinct cancer types, which were associated with genomic variation. The two subtypes indicated different clinical characteristics and biological processes in ccRCC. MPCS2, an aggressive subtype, led an advanced clinical stage and poorer survival of ccRCC patients. The activated oncogenic signaling pathway and metabolic signatures were responsible for cancer progression in the MPCS2 subtype. The MPCS2 subgroup suggested a higher tumor mutational burden and immune dysfunction state, resulting in a lower response to immunotherapy. The copy number variations of MPCS2 were significantly more frequent than those of MPCS1. In addition, the two subgroups exhibited distinct drug responsiveness, with MPCS2 being less responsive to multiple drugs. Finally, we established a subtype biomarker-based prognostic risk model that exhibited satisfactory performance in ccRCC patients. Conclusion: Melatonin regulator-related features could remodel functional pathways and the tumor immune microenvironment through genomic mutations and pathway regulation. Melatonin regulator-associated molecular subtypes enhance the understanding of the molecular characteristics of renal cancer and can guide clinical treatment. Activating the melatonergic system axis may improve the effect of immunotherapy for ccRCC.

Highly Reversible Lithium Metal Anode Enabled by 3D Lithiophilic-Lithiophobic Dual-Skeletons.

Lithium metal is a promising anode for high-energy-density lithium batteries, but its practical application is still hindered by intrinsic defects such as infinite volume expansion and uncontrollable dendrite growth. Herein, a dendrite-free 3D composite Li anode (Li-B@SSM) is prepared by mechanical rolling of lithiophilic LiB nanofibers supported by Li-B composite and lithiophobic stainless-steel mesh (SSM). Featuring hierarchical lithiophilic-lithiophobic dual-skeletons, the Li-B@SSM anode shows an ultrahigh Coulombic efficiency of 99.95% and a long lifespan of 900 h under 2 mA cm-2 /1 mAh cm-2 . It is demonstrated that the abnormally reversible Li stripping/plating processes should be closely related to the site-selective plating behavior and spatial confinement effect induced by the robust lithiophilic-lithiophobic dual-skeletons, which alleviates the volume changes, suppresses the growth of Li dendrites, and reduces the accumulation of "dead" Li. More importantly, the application feasibility of the Li-B@SSM anode is also confirmed in full batteries, of which the Li-B@SSM|LiFePO4 full cell shows a high capacity retention of 97.5% after 400 cycles while the Li-B@SSM|S pouch battery exhibits good cycle stability even under practically harsh conditions. This work paves the way for the facile and efficient fabrication of high-efficiency Li metal anodes toward practical applications.

Physical-layer key distribution based on commonly-driven laser synchronization with random modulation of drive light.

We propose and experimentally demonstrate a physical-layer key distribution scheme using commonly-driven laser synchronization with random modulation of drive light. Two parameter-matched semiconductor lasers injected by a common complex drive light are used as entropy sources for legitimate users. Legitimate users generate their own random signal by randomly time-division multiplexing of two random sequences with a certain duration according to individual control codes, and then independently modulate the drive light. Laser synchronization is achieved during time slots when the modulation sequences of two users are identical, and thus provide highly correlated randomness for extracting random numbers as shared keys. Experimental results show that the random modulation of the drive light reduces the correlation between the drive light and laser outputs. In addition, laser synchronization is sensitive to the modulation delay and then the latter can be used as an additional hardware parameter. These mean that security is enhanced. In addition, the proposed method has a short laser synchronization recovery time of lower than 1.1 ns, meaning a high rate of key distribution. The upper limit of final key rate of 2.55 Gb/s with a criterion of bit error rate of 1.68 × 10-3 is achieved in experiments. Our results provide a promising candidate for protecting the security of optical fiber communication.