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Key Points Fluorescence imaging can transform the way surgeries are performed, through the intraoperative identification of vital structures, lymph nodes and cancer in real time Near-infrared (NIR) fluorescence is particularly advantageous for use in clinical settings owing to improved depth penetration and low autofluorescence in the NIR wavelength range compared with shorter wavelengths Many targeted NIR fluorophores are currently in preclinical development; however, no cancer-targeted NIR fluorophores or devices for intraoperative NIR fluorescence detection of cancer have received commercial approval for human use Multiple early phase clinical trials are underway to evaluate targeted fluorophores for real-time, intraoperative cancer detection in humans The use of targeted fluorophores for the intraoperative detection of cancer might improve survival rates and functional outcomes in patients with cancer Currently, substantial regulatory challenges and clinical trial considerations constitute barriers for the adoption of fluorescence-guided surgery in clinical settings Intraoperative fluorescence enables highly specific real-time detection of tumours at the time of surgery. In particular, near-infrared (NIR) fluorescence is a promising tool currently being tested in clinical settings. Zhang et al . discuss the latest developments in NIR fluorophores, cancer-targeting strategies, and detection instrumentation for intraoperative cancer detection, as well as the challenges associated with their effective application in clinical settings. Over the past two decades, synergistic innovations in imaging technology have resulted in a revolution in which a range of biomedical applications are now benefiting from fluorescence imaging. Specifically, advances in fluorophore chemistry and imaging hardware, and the identification of targetable biomarkers have now positioned intraoperative fluorescence as a highly specific real-time detection modality for surgeons in oncology. In particular, the deeper tissue penetration and limited autofluorescence of near-infrared (NIR) fluorescence imaging improves the translational potential of this modality over visible-light fluorescence imaging. Rapid developments in fluorophores with improved characteristics, detection instrumentation, and targeting strategies led to the clinical testing in the early 2010s of the first targeted NIR fluorophores for intraoperative cancer detection. The foundations for the advances that underline this technology continue to be nurtured by the multidisciplinary collaboration of chemists, biologists, engineers, and clinicians. In this Review, we highlight the latest developments in NIR fluorophores, cancer-targeting strategies, and detection instrumentation for intraoperative cancer detection, and consider the unique challenges associated with their effective application in clinical settings.

To characterize the role of the circadian clock in mouse physiology and behavior, we used RNA-seq and DNA arrays to quantify the transcriptomes of 12 mouse organs over time. We found 43% of all protein coding genes showed circadian rhythms in transcription somewhere in the body, largely in an organ-specific manner. In most organs, we noticed the expression of many oscillating genes peaked during transcriptional \"rush hours\" preceding dawn and dusk. Looking at the genomic landscape of rhythmic genes, we saw that they clustered together, were longer, and had more spiiceforms than nonoscillating genes. Systems-level analysis revealed intricate rhythmic orchestration of gene pathways throughout the body. We also found oscillations in the expression of more than 1,000 known and novel noncoding RNAs (ncRNAs). Supporting their potential role in mediating clock function, ncRNAs conserved between mouse and human showed rhythmic expression in similar proportions as protein coding genes. Importantly, we also found that the majority of best-selling drugs and World Health Organization essential medicines directly target the products of rhythmic genes. Many of these drugs have short half-lives and may benefit from timed dosage. In sum, this study highlights critical, systemic, and surprising roles of the mammalian circadian clock and provides a blueprint for advancement in chronotherapy.

Serious floor heave in gob-side entry retaining (GER) with fully-mechanized gangue backfilling mining affects the transportation and ventilation safety of the mine. A theoretical mechanical model for the floor of gob-backfilled GER was established. The effects of the mechanical properties of floor strata, the granular compaction of backfilling area (BFA), the vertical support of roadside support body (RSB), and the stress concentration of the solid coal on the floor heave of the gob-backfilled GER were studied. The results show that the floor heave increases with the increase of the coal seam buried depth, and decreases with the increase of the floor rock elastic modulus. The development depth of the plastic zone decreases with the increase of the c and φ value of the floor rock, and increases with the increase of the stress concentration factor of the solid coal. The development depth of the plastic zone in the test mine reached 2.68 m. The field test and monitoring results indicate that the comprehensive control scheme of adjusting backfilling pressure, deep grouting reinforcement, shallow opening stress relief slots, and surface pouring can effectively control the floor heave. The roof-floor displacement is reduced by 73.8% compared to that with the original support scheme. The roadway section meets the design and application requirements when the deformation stabilizes, demonstrating the rationality of the mechanical model. The research results overcome the technical bottleneck of floor heave control of fully-mechanized backfilling GER, providing a reliable basis for the design of a floor heave control scheme.

Development of a safe and economical roadside support body (RSB) material is the key to successful backfilling gob-side entry retaining (GER). By means of laboratory tests, this paper studied the effects of the water-cement ratio, aggregate content, and age on the contractibility and resistance increasing speed, compressive strength, and postpeak carrying capacity of the concrete with gangues as an aggregate. It also discussed the rationality and adaptability of gangue concrete as a RSB material for backfilling GER. The experimental results show that the compressive strength of gangue concrete increases with age, and that the strength of gangue concrete demonstrates a nonlinear decreasing trend with the increase of the cementing material’s water-cement ratio. The water-cement ratio in the range of 0.46–0.60 has the most significant regulation effect on the strength of gangue concrete. Mixing with a certain amount of coal gangue enhances the postpeak carrying capacity of concrete, preventing the sample from impact failure. The field experimental results report that as a RSB material, gangue concrete can meet the design and application requirements of GER with gangue backfilling mining. A RSB material featuring high safety, high waste utilization rate, fast construction speed, and low costs is provided.

To counter the technical difficulties faced by gob-side entry retaining (GER) under multiple complex mining geological conditions in China, this paper introduces a GER method with fully mechanized gangue backfilling mining. A similar materials simulation experiment was conducted to simulate the gob-backfilled GER process by using the similar model test system containing an independently developed horizontal pushing load device. The experimental results show that the compaction speed of the backfilling area (BFA) can be improved, and the main roof subsidence can be reduced by increasing the horizontal pushing load and reducing the attenuation rate of the stress in BFA. The designed roadside backfill body (RBB) containing a flexible cushion is adaptive to the given deformation of the main roof, thus reducing the stress concentration of the RBB. The field test results show that when a 2 MPa horizontal pushing load is exerted in the BFA, arranging a 200 mm high-water-material flexible cushion can cause the BFA to swiftly change to the compaction stage. After stabilized deformation, the roadway section satisfies the design and application requirements. The feasibility and rationality of the GER with the fully mechanized gangue backfilling mining are proved, providing a safe, efficient, and environmentally friendly mining method without using a coal pillar.

Interoperability testing and analysis tools provide a means for achieving and assuring the integrity of multivendor intelligent electronic devices (IEDs) data exchanges. However, the testing and analysis are very time consuming and error prone, and these problems worsen when a substation becomes large and complex during the engineering process, commission, replacement, maintenance, and extension. To address this challenge, this paper presents a virtual digital substation test system (VDSTS) with interoperability analysis tools for assessing and identifying the engineering challenges for the multiple-vendors digital substation. This VDSTS consists of three parts: (i) A virtual digital substation modelling for generating real-time digital substation primary plant operation and fault conditions, (ii) a standard IEC 61850-based substation protection, automation, and control (PAC) system architecture with multivendor IEDs and bay solutions, and (iii) multivendor Substation Configuration description Language (SCL) tools and in-house built data visualisation tool. The study focuses on the interoperability testing of sampled values (SV), generic object-oriented substation events (GOOSE), and manufacturing message specification (MMS) communication services, as defined in IEC 61850. The main issues identified are compatibility issues of SCL tools, protocol implementation issues, different information models, and application limitations. The outcomes will help utilities to reduce the risks associated with the general rollout of digital substations.

With the global net-zero strategy implementation, decarbonisation of transport by massive deployment of electric vehicles (EVs) has been considered to be an essential solution. However, charging EVs and integration into electricity grids is going to be a fundamental challenge to future electricity systems. Hence, in this situation, how to effectively deploy massive numbers of EVs, and in the meantime what can be developed to deliver vehicle-to-grid (V2G) services, become a fundamental yet interesting tech-economical issues. Furthermore, uncertainty in lack of vehicle availability and EV battery degradation could lead to revenue loss when using EVs as ancillary services aggregators. With such considerations, this paper presents a new optimised V2G aggregator scheduling service that has taken into consideration of a number of risks, including EV availability and battery degradation through conditional value-at-risk. The proposed method for V2G scheduling service, as an independent aggregator, is formulated as a bi-level optimisation problem. The performance of the proposed method is to be evaluated through case studies on the Birmingham International Airport parking lot with onsite renewable generation. Uncertainties of EVs and the differences in weekdays and weekends are also compared.

Many microbial pathogens form biofilms, assemblages of polymeric compounds that play a crucial role in establishing infections. The biofilms of Fusarium species also contribute to high antifungal resistance. Using our collection of 29 clinical Fusarium isolates, we focused on characterizing differences in thermotolerance, anaerobic growth, and biofilm formation across four Fusarium species complexes commonly found in clinical settings. We investigated the role of carbon sources, temperature, and fungal morphology on biofilm development. Using fluorescence microscopy, we followed the stages of biofilm formation. Biofilms were screened for sensitivity/resistance to the antifungals voriconazole (VOR), amphotericin B (AmB), and 5-fluorocytosine (5-FC). Our findings revealed generally poor thermotolerance and growth under anaerobic conditions across all Fusarium species. VOR was more effective than AmB in controlling biofilm formation, but the combination of VOR, AmB, and 5-FC significantly reduced biofilm formation across all species. Additionally, Fusarium biofilm formation varied under non-glucose carbon sources, highlighting the species’ adaptability to different nutrient environments. Notably, early stage biofilms were primarily composed of lipids, while polysaccharides became dominant in late-stage biofilms, suggesting a dynamic shift in biofilm composition over time.