Personalized analysis of human cancer multi-omics for precision oncology.

Multi-omics technologies, encompassing genomics, proteomics, and transcriptomics, provide profound insights into cancer biology. A fundamental computational approach for analyzing multi-omics data is differential analysis, which identifies molecular distinctions between cancerous and normal tissues. Traditional methods, however, often fail to address the distinct heterogeneity of individual tumors, thereby neglecting crucial patient-specific molecular traits. This shortcoming underscores the necessity for tailored differential analysis algorithms, which focus on particular patient variations. Such approaches offer a more nuanced understanding of cancer biology and are instrumental in pinpointing personalized therapeutic strategies. In this review, we summarize the principles of current individualized techniques. We also review their efficacy in analyzing cancer multi-omics data and discuss their potential applications in clinical practice.

Tyrosine nitration enhances the allergenic potential of house dust mite allergen Der p 2.

Nitration of allergenic proteins caused by atmospheric pollutants O3 and NO2 may enhance their allergenic potential. In the study, the influence of nitration was investigated on the allergenicity of Der p 2, which is a main allergen from house dust mites and plays an important role in allergenic rhinitis and asthma. The results reveal that nitrated Der p 2 enhanced the IgE-binding capacity, upregulated the mRNA expression and release of IL-6 and IL-8 from bronchial epithelial cells, and induced higher levels of specific-IgE, TH2 cytokines and white blood cells in mice. Besides, nitrated Der p 2 caused more severe oxidative stress and allergenic symptoms in mice. It is concluded that nitration enhanced the allergenicity of Der p 2 through not only directly inducing higher amount of specific-IgE and stronger responses of TH2 cytokines, but also indirectly aggravating allergic symptoms by oxidative stress and adjuvant-like activation airway epithelial cells. The study suggests that the contribution of nitration to the promotion in allergenicity should not be ignored when precisely assessing the risk of house dust mite allergens in real environment.

Correlation between Heteroatom Coordination and Hydrogen Evolution for Single-site Pt on Carbon-based Nanocages.

The electrocatalytic performance of single-site catalysts (SSCs) is closely correlated with the electronic structure of metal atoms. Herein we construct a series of Pt SSCs on heteroatom-doped hierarchical carbon nanocages, which exhibit increasing hydrogen evolution reaction (HER) activities along S-doped, P-doped, undoped and N-doped supports. Theoretical simulation indicates a multi-H-atom adsorption process on Pt SSCs due to the low coordination, and a reasonable descriptor is figured out to evaluate the HER activities. Relative to C-coordinated Pt, N-coordinated Pt has higher reactivity due to the electron transfer of N-to-Pt, which enriches the density of states of Pt 5d orbital near the Fermi level and facilitates the capturing of protons, just the opposite to the situations for P- and S-coordinated ones. The stable N-coordinated Pt originates from the kinetic stability throughout the multi-H-atom adsorption process. This finding provides a significant guidance for rational design of advanced Pt SSCs on carbon-based supports.

Oxygen-Bridged Cu Binuclear Sites for Efficient Electrocatalytic CO2 Reduction to Ethanol at Ultralow Overpotential.

Electrocatalytic CO2 reduction (CO2RR) to alcohols offers a promising strategy for converting waste CO2 into valuable fuels/chemicals but usually requires large overpotentials. Herein, we report a catalyst comprising unique oxygen-bridged Cu binuclear sites (CuOCu-N4) with a Cu···Cu distance of 3.0-3.1 Å and concomitant conventional Cu-N4 mononuclear sites on hierarchical nitrogen-doped carbon nanocages (hNCNCs). The catalyst exhibits a state-of-the-art low overpotential of 0.19 V (versus reversible hydrogen electrode) for ethanol and an outstanding ethanol Faradaic efficiency of 56.3% at an ultralow potential of -0.30 V, with high-stable Cu active-site structures during the CO2RR as confirmed by operando X-ray adsorption fine structure characterization. Theoretical simulations reveal that CuOCu-N4 binuclear sites greatly enhance the C-C coupling at low potentials, while Cu-N4 mononuclear sites and the hNCNC support increase the local CO concentration and ethanol production on CuOCu-N4. This study provides a convenient approach to advanced Cu binuclear site catalysts for CO2RR to ethanol with a deep understanding of the mechanism.

Optimizing nitrogen application position to change root distribution in soil and regulate maize growth and yield formation in a wide-narrow row cropping system: pot and field experiments.

The wide-and narrow-row cropping technology used for maize has the advantages of protecting cultivated soil and improving the population structure in maize fields. However, the relationship between nitrogen application position and root interactions has not been determined. Through pot and field experiments, we evaluated the effects of two nitrogen application positions ((narrow row nitrogen application (RC) and wide row nitrogen application (RN)) and two nitrogen application regimens ((high nitrogen(HN) and low nitrogen(LN)) on root growth and yield composition of wide-narrow row maize during the flowering and harvest stages. In field experiments, RC increased the biomass, length and surface area of competing roots (narrow-row roots, CR) at the flowering stage. The yield and agronomic efficiency of N(AEN) and partial factor productivity of N(PFPN) were increased by RN compared to RC under HN, However, the AEN under LN was significantly lower; There was no significant effect on maize growth and biomass allocation at the same level of application of N. At the flowering stage, the results of CR and non-competing roots (wide-row roots, NCR) was consistent under pot experiments and the field experiments, and the yield under RN was also higher than that under RC, although the difference was not significant. Furthermore, according to the principal component analysis and correlation analysis, the competing roots were the main factor influencing yield and AEN. In conclusion, our study showed that RN is a useful fertilization method to improve overall productivity. All in all, how roots coordinate neighbors and nitrogen spatial heterogeneity is a complex ecological process, and its trophic behavior deserves further study.

A Multicenter Prospective Randomized Controlled Study of a New Corneal Wetting Agent During Ophthalmologic Surgery.

INTRODUCTION: A multicenter prospective randomized controlled study was used to investigate the effect and safety of a new corneal wetting agent called the Corneal Surface Viscoelastic Protector (CsVisc, Success Bio-Tech Co., Ltd, China), on the corneal epithelium during ophthalmic surgery by comparison with the commercially available Cornea Protect (CP, Valeant Med Sp. zo. o. Leobendorf, Austria). METHODS: This multicenter prospective randomized controlled study comprised patients scheduled for cataract surgery and pars plana vitrectomy. The patients were randomly assigned to receive either a new corneal wetting agent (CsVisc) or Cornea Protect (CP, Valeant Med Sp. zo. o. Leobendorf, Austria). Optical clarity during surgery, application frequency, duration of effect, diffusion time of corneal wetting agents, fluorescein staining, intraocular pressure (IOP), tear-film break-up time (TBUT), and Schirmer I test (SIT) were assessed. Adverse events were noted on the designated patient case report forms. RESULTS: A total of 149 eyes (149 patients, mean age 62 years; range 25-80 years) were included in the study. There were 74 eyes in the control group and 75 eyes in the study group. In patients who underwent vitrectomy, the frequency of application was 1.62 ± 1.03 in the study group and 1.39 ± 0.66 in the control group, with no significant difference (P = 0.399), and the duration of effect was 19.16 ± 6.94 min in the study group and 19.06 ± 7.22 min in the control group, with no significant difference (P = 0.835). The optical clarity of the study group was not significantly different from that of the control group (P = 0.485). In patients who underwent cataract surgery, the frequency of application was 1.10 ± 0.38 in the study group and 1.07 ± 0.26 in the control group, and the difference was not significant (P = 0.950). The difference between the duration of effect in the study group (8.32 ± 2.50 min) and the control group (7.63 ± 2.52 min) was not significant (P = 0.310). The difference in optical clarity scores between the two groups was not statistically significant (P = 0.600). Among all patients in this study, the diffusion time of the corneal wetting agent was 14.97 ± 10.07 s in the control group and 11.23 ± 8.41 s in the study group, with a statistically significant difference (p = 0.008). The frequency of adverse events was 20.00% (15/75) in the study group and 14.86% (11/74) in the control group, with no statistically significant difference (P = 0.409). There were no serious adverse events related to the test medical device or causing patients to withdraw from the study. CONCLUSIONS: The CsVisc is safe and effective in preventing intraoperative corneal epithelial damage due to corneal dryness and can be comparable to the CP. In addition, the CsVisc has a shorter diffusion time.

Advanced silk materials for musculoskeletal tissue regeneration.

Musculoskeletal diseases are the leading causes of chronic pain and physical disability, affecting millions of individuals worldwide. Over the past two decades, significant progress has been made in the field of bone and cartilage tissue engineering to combat the limitations of conventional treatments. Among various materials used in musculoskeletal tissue regeneration, silk biomaterials exhibit unique mechanical robustness, versatility, favorable biocompatibility, and tunable biodegradation rate. As silk is an easy-to-process biopolymer, silks have been reformed into various materials formats using advanced bio-fabrication technology for the design of cell niches. Silk proteins also offer active sites for chemical modifications to facilitate musculoskeletal system regeneration. With the emergence of genetic engineering techniques, silk proteins have been further optimized from the molecular level with other functional motifs to introduce new advantageous biological properties. In this review, we highlight the frontiers in engineering natural and recombinant silk biomaterials, as well as recent progress in the applications of these new silks in the field of bone and cartilage regeneration. The future potentials and challenges of silk biomaterials in musculoskeletal tissue engineering are also discussed. This review brings together perspectives from different fields and provides insight into improved musculoskeletal engineering.

Directional Emission from Electrically Injected Exciton-Polaritons in Perovskite Metasurfaces.

We present a new approach to achieving strong coupling between electrically injected excitons and photonic bound states in the continuum of a dielectric metasurface. Here a high-finesse metasurface cavity is monolithically patterned in the channel of a perovskite light-emitting transistor to induce a large Rabi splitting of ∼200 meV and more than 50-fold enhancement of the polaritonic emission compared to the intrinsic excitonic emission of the perovskite film. Moreover, the directionality of polaritonic electroluminescence can be dynamically tuned by varying the source-drain bias, which induces an asymmetric distribution of exciton population within the transistor channel. We argue that this approach provides a new platform to study strong light-matter interactions in dispersion engineered photonic cavities under electrical injection and paves the way to solution-processed electrically pumped polariton lasers.

High-Dispersive Pd Nanoparticles on Hierarchical N-Doped Carbon Nanocages to Boost Electrochemical CO2 Reduction to Formate at Low Potential.

Electrochemical CO2 reduction reaction (CO2 RR) to value-added chemicals/fuels is an effective strategy to achieve the carbon neutral. Palladium is the only metal to selectively produce formate via CO2 RR at near-zero potentials. To reduce cost and improve activity, the high-dispersive Pd nanoparticles on hierarchical N-doped carbon nanocages (Pd/hNCNCs) are constructed by regulating pH in microwave-assisted ethylene glycol reduction. The optimal catalyst exhibits high formate Faradaic efficiency of >95% within -0.05-0.30 V and delivers an ultrahigh formate partial current density of 10.3 mA cm-2 at the low potential of -0.25 V. The high performance of Pd/hNCNCs is attributed to the small size of uniform Pd nanoparticles, the optimized intermediates adsorption/desorption on modified Pd by N-doped support, and the promoted mass/charge transfer kinetics arising from the hierarchical structure of hNCNCs. This study sheds light on the rational design of high-efficient electrocatalysts for advanced energy conversion.

Site-specific tyrosine nitration of group 1 allergens of house dust mite Dermatophagoides farinae (Der f 1) and Dermatophagoides pteronyssinus (Der p 1) in indoor dusts.

Nitration can enhance the allergenicity of proteins. The nitration status of house dust mite (HDM) allergens in indoor dusts, however, remains to be elucidated. In the study, site-specific tyrosine nitration degrees of the two important HDM allergens Der f 1 and Der p 1 in indoor dust samples were investigated by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The measured concentrations of native and nitrated allergens in the dusts were in the range of 0.86-29 µg g-1 for Der f 1 and from below the detection limit to 29 µg g-1 for Der p 1. Site-specific analysis revealed that all ten tyrosine residues in Der f 1 and Der p 1 were nitrated to different degrees in the investigated samples. The preferred nitration sites were Y56 in Der f 1 and Y37 in Der p 1 with the nitration degrees of 7.6-84% and 17-96% among the detected tyrosine residues, respectively. The measurements reveal high site-specific nitration degrees for tyrosine in Der f 1 and Der p 1 detected in the indoor dust samples. Further investigations are required to find out if the nitration really aggravates the health effects of HDM allergens and if the effects are tyrosine site-dependent.

Perovskite quantum dot one-dimensional topological laser.

Various topological laser concepts have recently enabled the demonstration of robust light-emitting devices that are immune to structural deformations and tolerant to fabrication imperfections. Current realizations of photonic cavities with topological boundaries are often limited by outcoupling issues or poor directionality and require complex design and fabrication that hinder operation at small wavelengths. Here we propose a topological cavity design based on interface states between two one-dimensional photonic crystals with distinct Zak phases. Using a few monolayers of solution-processed all-inorganic cesium lead halide perovskite quantum dots as the ultrathin gain medium, we demonstrate a lithography-free, vertical-emitting, low-threshold, and single-mode laser emitting in the green. We show that the topological laser, akin to vertical-cavity surface-emitting lasers (VCSELs), is robust against local perturbations of the multilayer structure. We argue that the design simplicity and reduction of the gain medium thickness enabled by the topological cavity make this architecture suitable for low-cost and efficient quantum dot vertical emitting lasers operating across the visible spectral region.

Prioritizing prognostic-associated subpopulations and individualized recurrence risk signatures from single-cell transcriptomes of colorectal cancer.

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies. There are few recurrence risk signatures for CRC patients. Single-cell RNA-sequencing (scRNA-seq) provides a high-resolution platform for prognostic signature detection. However, scRNA-seq is not practical in large cohorts due to its high cost and most single-cell experiments lack clinical phenotype information. Few studies have been reported to use external bulk transcriptome with survival time to guide the detection of key cell subtypes in scRNA-seq data. We proposed scRankXMBD, a computational framework to prioritize prognostic-associated cell subpopulations based on within-cell relative expression orderings of gene pairs from single-cell transcriptomes. scRankXMBD achieves higher precision and concordance compared with five existing methods. Moreover, we developed single-cell gene pair signatures to predict recurrence risk for patients individually. Our work facilitates the application of the rank-based method in scRNA-seq data for prognostic biomarker discovery and precision oncology. scRankXMBD is available at https://github.com/xmuyulab/scRank-XMBD. (XMBD:Xiamen Big Data, a biomedical open software initiative in the National Institute for Data Science in Health and Medicine, Xiamen University, China.).

Phase-Change Perovskite Microlaser with Tunable Polarization Vortex.

Metasurfaces supporting optical bound states in the continuum (BICs) are emerging as simple and compact optical cavities to realize polarization-vortex lasers. The winding of the polarization around the singularity defines topological charges which are generally set by the cavity design and cannot be altered without changing geometrical parameters. Here, a subwavelength-thin phase-change halide perovskite BIC metasurface functioning as a tunable polarization vortex microlaser is demonstrated. Upon the perovskite structural phase transitions, both its refractive index and gain vary substantially, inducing reversible and bistable switching between distinct polarization vortexes underpinned by opposite topological charges. Dynamic tuning and switching of the resulting vector beams may find use in microscopy imaging, particle trapping and manipulation, and optical data storage.

Polarization-Tunable Perovskite Light-Emitting Metatransistor.

Emerging immersive visual communication technologies require light sources with complex functionality for dynamic control of polarization, directivity, wavefront, spectrum, and intensity of light. Currently, this is mostly achieved by free space bulk optic elements, limiting the adoption of these technologies. Flat optics based on artificially structured metasurfaces that operate at the sub-wavelength scale are a viable solution, however, their integration into electrically driven devices remains challenging. Here, a radically new approach to monolithic integration of a dielectric metasurface into a perovskite light-emitting transistor is demonstrated. It is shown that nanogratings directly structured on top of the transistor channel yield an 8-fold increase of electroluminescence intensity and dynamic tunability of polarization. This new light-emitting metatransistor device concept opens unlimited opportunities for light management strategies based on metasurface design and integration.

House dust mite allergens and nitrated products: Identification and risk assessment in indoor dust.

Air pollutants can potentially lead to nitration of allergic proteins, thus promoting sensitization of these allergens. However, little is currently known about the nitration status of house dust mite (HDM) allergens. We identified the occurrence of nitrated products of two major HDM allergens Der f 1 and Der p 1 in dust samples collected from college dormitories in eastern China and assessed their associated health risk. The results showed that both non-nitrated and nitrated forms of the two allergens were detected in the dust in the range of non-detected (ND)-10.6, 1.44-15.4, ND-22.4, ND-7.28 µg/g for non-nitrated Der f 1, nitrated Der f 1, non-nitrated Der p 1 and nitrated Der p 1, respectively. The median rates of nitration were determined as 74.0% for Der f 1 and 20.4% for Der p 1 at consideration of one nitration site. Further analysis reveals that the levels of HDM allergens and their nitrated products were found to be generally higher during winter, in dormitories of lower altitude and with female occupants. Furthermore, the calculated risk indexes were at considerably high levels. Our findings suggest that nitrated HDM allergens have already accumulated in the environment at such significant levels and their associated health risk calls for our immediate attention.

Resonant Enhancement of Polymer-Cell Optostimulation by a Plasmonic Metasurface.

Organic semiconductors have shown great potential as efficient bioelectronic materials. Specifically, photovoltaic polymers such as the workhorse poly(thiophene) derivatives, when stimulated with visible light, can depolarize neurons and generate action potentials, an effect that has been also employed for rescuing vision in blind rats. In this context, however, the coupling of such materials with optically resonant structures to enhance those photodriven biological effects is still in its infancy. Here, we employ the optical coupling between a nanostructured metasurface and poly(3-hexylthiophene) (P3HT) to improve the bioelectronic effects occurring upon photostimulation at the abiotic-biotic interface. In particular, we designed a spectrally tuned aluminum metasurface that can resonate with P3HT, hence augmenting the effective field experienced by the polymer. In turn, this leads to an 8-fold increase in invoked inward current in cells. This enhanced activation strategy could be useful to increase the effectiveness of P3HT-based prosthetic implants for degenerative retinal disorders.

Utility of diffusion weighted imaging-based radiomics nomogram to predict pelvic lymph nodes metastasis in prostate cancer.

BACKGROUND: Preoperative pelvic lymph node metastasis (PLNM) prediction can help clinicians determine whether to perform pelvic lymph node dissection (PLND). The purpose of this research is to explore the feasibility of diffusion-weighted imaging (DWI)-based radiomics for preoperative PLNM prediction in PCa patients at the nodal level. METHODS: The preoperative MR images of 1116 pathologically confirmed lymph nodes (LNs) from 84 PCa patients were enrolled. The subjects were divided into a primary cohort (67 patients with 192 positive and 716 negative LNs) and a held-out cohort (17 patients with 43 positive and 165 negative LNs) at a 4:1 ratio. Two preoperative pelvic lymph node metastasis (PLNM) prediction models were constructed based on automatic LN segmentation with quantitative radiological LN features alone (Model 1) and combining radiological and radiomics features (Model 2) via multiple logistic regression. The visual assessments of junior (Model 3) and senior (Model 4) radiologists were compared. RESULTS: No significant difference was found between the area under the curve (AUCs) of Models 1 and 2 (0.89 vs. 0.90; P = 0.573) in the held-out cohort. Model 2 showed the highest AUC (0.83, 95% CI 0.76, 0.89) for PLNM prediction in the LN subgroup with a short diameter ≤ 10 mm compared with Model 1 (0.78, 95% CI 0.70, 0.84), Model 3 (0.66, 95% CI 0.52, 0.77), and Model 4 (0.74, 95% CI 0.66, 0.88). The nomograms of Models 1 and 2 yielded C-index values of 0.804 and 0.910, respectively, in the held-out cohort. The C-index of the nomogram analysis (0.91) and decision curve analysis (DCA) curves confirmed the clinical usefulness and benefit of Model 2. CONCLUSIONS: A DWI-based radiomics nomogram incorporating the LN radiomics signature with quantitative radiological features is promising for PLNM prediction in PCa patients, particularly for normal-sized LNM.

Outcomes of Transscleral Two-Point Fixation Versus Closed Continuous-Loop Four-Point Fixation of Intraocular Lens in Subluxated Lens Secondary to Marfan Syndrome.

INTRODUCTION: To compare the outcome of two different transscleral fixation approaches for posterior chamber intraocular lens (IOL) implantation, a two-point fixation of the Sensar (Allergan) or CZ70BD (Alcon) IOL and a four-point fixation of the Akreos Adapt (Bausch & Lomb) foldable IOL, for treatment of subluxated lenses in Marfan syndrome (MFS). METHODS: Fifty-three eyes of 33 consecutive patients with subluxated lenses secondary to MFS were studied. Eighteen patients with MFS (30 eyes) received two-point fixation of the Sensar (16 patients, 26 eyes) or CZ70BD (2 patients, 4 eyes) IOL, and 15 patients with MFS (23 eyes) received four-point fixation of the Akreos Adapt IOL. Preoperative and postoperative ophthalmologic examinations were performed. A primary outcome measure of postoperative complication was studied. RESULTS: The mean preoperative best corrected visual acuity (BCVA) in the two-point group was 0.68 ± 0.38 logarithm of the minimum angle of resolution (logMAR), and it improved to 0.30 ± 0.32 logMAR at the final follow-up (p < 0.05). The mean preoperative BCVA in the four-point group was 0.68 ± 0.45 logMAR, and it improved to 0.28 ± 0.28 logMAR at the final follow-up (p < 0.05). The BCVA results did not differ significantly between groups. The intraocular pressure was increased at the final follow-up in the two-point group (p < 0.05). Transscleral two-point fixation of IOL has relatively high incidences of pupillary capture of the IOL. CONCLUSION: The closed continuous-loop transscleral four-point fixation of the Akreos Adapt foldable IOL is more suitable than two-point fixation of a two-haptic IOL in treating subluxated lenses due to MFS.

INCIDENCE AND RISK FACTORS OF POSTOPERATIVE ENDOPHTHALMITIS AFTER PRIMARY SURGICAL REPAIR COMBINED WITH INTRAOCULAR FOREIGN BODY REMOVAL.

PURPOSE: To analyze the incidence and risk factors of postoperative endophthalmitis after primary surgical repair and intraocular foreign body (IOFB) removal within 24 hours of injury. METHODS: The records of all patients treated surgically for open globe injury and IOFB removal at the Eye Hospital of Shandong First Medical University between January 1, 2015, and June 30, 2020, were retrospectively reviewed. Variables included time from injury to operation, cause of injury, details of surgical repair, and follow-up. The incidence and risk factors of endophthalmitis after IOFB removal were studied. RESULTS: During 5 years, 99 patients with IOFB were reviewed. Of these, 19 patients were diagnosed with endophthalmitis on admission, and 5 were suspected of having endophthalmitis during operation. Fifty-four cases had no clinical signs of endophthalmitis on admission and during operation and were treated with operation within 24 hours after the injury. Two patients (2 of 54; 3.70%) developed endophthalmitis after IOFB removal, and the causative agent in both cases was Bacillus cereus. CONCLUSION: The incidence of infectious endophthalmitis after primary surgical repair combined with IOFB removal (≤24 hours) was 3.70% in patients who received a series of standard treatments, and B. cereus infection might be a risk factor.

RNAi of Sterol Δ24-Isomerase Implicated Its Involvement in Physalin Biosynthesis in Physalis angulata L.

Physalis angulata is a renowned traditional Chinese medicine for the treatment of various conditions. Physalin is the major type of bioactive constituents conferring medicinal properties of P. angulata. Despite the medicinal importance, the pathways leading to physalin are largely unknown. In this study, we employed a transcriptomic approach to identify a Pa24ISO gene from P. angulata. Through heterologous expression in yeast, Pa24ISO was revealed to catalyze an isomerization reaction in converting 24-methylenecholesterol to 24-methyldesmosterol. Real-time PCR analysis showed that the abundance of Pa24ISO transcripts correlated with the accumulation pattern of physalin B in different tissues of P. angulata. A direct role of Pa24ISO in channeling of 24-methylenecholesterol for physalin B biosynthesis was illustrated by suppressing the gene in P. angulata via the VIGS approach. Down-regulation of Pa24ISO led to reduced levels of 24-methyldesmosterol and physalin B, accompanied with an increase of campesterol content in P. angulata. The results supported that 24ISO is involved in physalin biosynthesis in plants.