Active manipulation for Goos-Hänchen shift of guided-wave via a metasurface of silicon-nanoscale semi-spheres on SOI waveguide.

Goos-Hänchen shift of total internal reflection (TIR) is the light beam movement without external driving, so envisioned to have potential manipulation of optical beams. In this article, with a silicon-on-insulator (SOI) waveguide corner structure, a variable equivalent permittivity of guided wave is modelled, and then the equivalent electric polarizabilities and the Goos-Hänchen shift of guided wave are modelled. Consequently, with a 2.0-µm SOI waveguide corner structure and an abrupt phase change of ∼0.5π caused by a vertically inserted metasurface of nanoscale semi-spheres having a 450-nm radius can reach the GH shifts of 2.1 µm for TE- and TM-mode, respectively, which are verified by both the FDTD simulation results of 1.93 µm with a reflectivity of about 62% and the experimental results of 2.0 µm with ∼60%. Therefore, this work has efficiently modelled the optical feature response of semi-sphere metasurface to guided wave and the active manipulation for the GH shifts of guided-wave, opening more opportunities to develop the new functionalities and devices for Si-based photonic integrated circuit (PIC) applications.

Epidemiologic changes of infectious diseases in the post-SARS era in China, 2004-2018.

OBJECTIVES: To outline 44 major infectious diseases in the post-SARS (severe acute respiratory syndrome) in China and describe their long-term trends and changes by age, sex, epidemic season, and province. BACKGROUND: After the outbreak of severe acute respiratory syndrome (SARS) in 2003, with the change of infectious disease prevention and control system and the improvement of residents' quality of life, the incidence and mortality of infectious diseases have undergone major changes. METHODS: The data of 44 major infectious diseases in China from 2004 to 2018 were obtained from the monthly analysis report of the China Information System for Disease Control and Prevention (CISDCP) and the Public Health Science Data Center. Joinpoint r regression models were used to examine trends in incidence and mortality for 44 major and important infectious diseases from 2004 to 2018. RESULTS: From 2004 to 2018, 20,105, 500, 772 patients (10, 306, 546, 523 males and 9, 798, 954, 249 females) were diagnosed with 44 major infectious diseases. The overall incidence of 44 infectious diseases increased significantly from 294.6 per 100,000 people in 2004 to 479.1 per 100,000 people in 2010, with 7.9% APC (95% CI 5.2% -10.7%, P < 0.001), then slowed, and then increased to 561.2 per 100,000 people in 2018, with 1.5% APC (-0.1%-3.2%, P = 0.070). The overall mortality rose significantly, from 0.49 to 1.13 per 100,000 people between 2004 and 2011, with an APC increase of 11.6% (7.7% -15.6%, P < 0.001), and then remained stable until 2018. Among these, the prevalence of vaccine-preventable diseases and gastrointestinal & enteroviral diseases remained high and increased year by year. Patients with zoonotic diseases have the greatest risk of death, while patients with sexually transmitted and blood-borne diseases have the greatest number of deaths. Incidence rates vary considerably across geographic regions. Western China has a disproportionate burden of infectious diseases compared with eastern regions. CONCLUSIONS: After the event of SARS in 2003, infectious disease preventing and controlling model has undergone major changes in China, and certain achievements have been made in this field. Although overall morbidity and case fatality rates are still rising, they have leveled off. In reducing the disproportionate disease burden in the western region, expanding vaccination programs, preventing further increases in rates of sexually transmitted diseases, renewing efforts for emerging and persistent infectious diseases, and addressing seasonal and unpredictable outbreaks (such as the COVID-19 pandemic), there are still remain many challenges.

Impact of outdoor air pollution on the incidence of pertussis in China: a time-series study.

BACKGROUND: The increasing number of pertussis cases worldwide over the past two decades has challenged healthcare workers, and the role of environmental factors and climate change cannot be ignored. The incidence of pertussis has increased dramatically in mainland China since 2015, developing into a serious public health problem. The association of meteorological factors on pertussis has attracted attention, but few studies have examined the impact of air pollutants on this respiratory disease. METHODS: In this study, we analyzed the relationship between outdoor air pollution and the pertussis incidence. The study period was from January 2013 to December 2018, and monthly air pollutant data and the monthly incidence of patients in 31 provinces of China were collected. Distributed lag nonlinear model (DLNM) analysis was used to estimate the associations between six air pollutants and monthly pertussis incidence in China. RESULTS: We found a correlation between elevated pertussis incidence and short-term high monthly CO2 and O3 exposure, with a 10 µg/m3 increase in NO2 and O3 being significantly associated with increased pertussis incidence, with RR values of 1.78 (95% CI: 1.29-2.46) and 1.51 (95% CI: 1.16-1.97) at a lag of 0 months, respectively. Moreover, PM2.5 and SO2 also played key roles in the risk of pertussis surged. These associations remain significant after adjusting for long-term trend, seasonality and collinearity. CONCLUSIONS: Overall, these data reinforce the evidence of a link between incidence and climate identified in regional and local studies. These findings also further support the hypothesis that air pollution is responsible for the global resurgence of pertussis. Based on this we suggest that public health workers should be encouraged to consider the risks of the environment when focusing on pertussis prevention and control.

Intramuscular Microvascular Flow Sensing for Flap Monitoring in a Porcine Model of Arterial and Venous Occlusion.

BACKGROUND: Commercially available near infrared spectroscopy devices for continuous free flap tissue oxygenation (StO2) monitoring can only be used on flaps with a cutaneous component. Additionally, differences in skin quality and pigmentation may alter StO2 measurements. Here, we present a novel implantable heat convection probe that measures microvascular blood flow for peripheral monitoring of free flaps, and is not subject to the same issues that limit the clinical utility of near-infrared spectroscopy. METHODS: The intratissue microvascular flow-sensing device includes a resistive heater, 4 thermistors, a small battery, and a Bluetooth chip, which allows connection to a smart device. Convection of applied heat is measured and mathematically transformed into a measurement of blood flow velocity. This was tested alongside Vioptix T.Ox in a porcine rectus abdominis myocutaneous flap model of arterial and venous occlusion. After flap elevation, the thermal device was deployed intramuscularly, and the cutaneous T.Ox device was applied. Acland clamps were alternately applied to the flap artery and veins to achieve 15 minutes periods of flap ischemia and congestion with a 15 minutes intervening recovery period. In total, five devices were tested in three flaps in three separate pigs over 16 vaso-occlusive events. RESULTS: Flow measurements were responsive to both ischemia and congestion, and returned to baseline during recovery periods. Flow measurements corresponded closely with measured StO2. Cross-correlation at zero lag showed agreement between these two sensing modalities. Two novel devices tested simultaneously on the same flap showed only minor variations in flow measurements. CONCLUSION: This novel probe is capable of detecting changes in tissue microcirculatory blood flow. This device performed well in a swine model of flap ischemia and congestion, and shows promise as a potentially useful clinical tool. Future studies will investigate performance in fasciocutaneous flaps and characterize longevity of the device over a period of several days.

Photocurable bioresorbable adhesives as functional interfaces between flexible bioelectronic devices and soft biological tissues.

Flexible electronic/optoelectronic systems that can intimately integrate onto the surfaces of vital organ systems have the potential to offer revolutionary diagnostic and therapeutic capabilities relevant to a wide spectrum of diseases and disorders. The critical interfaces between such technologies and living tissues must provide soft mechanical coupling and efficient optical/electrical/chemical exchange. Here, we introduce a functional adhesive bioelectronic-tissue interface material, in the forms of mechanically compliant, electrically conductive, and optically transparent encapsulating coatings, interfacial layers or supporting matrices. These materials strongly bond both to the surfaces of the devices and to those of different internal organs, with stable adhesion for several days to months, in chemistries that can be tailored to bioresorb at controlled rates. Experimental demonstrations in live animal models include device applications that range from battery-free optoelectronic systems for deep-brain optogenetics and subdermal phototherapy to wireless millimetre-scale pacemakers and flexible multielectrode epicardial arrays. These advances have immediate applicability across nearly all types of bioelectronic/optoelectronic system currently used in animal model studies, and they also have the potential for future treatment of life-threatening diseases and disorders in humans.

Active secretion of a thermostable transglutaminase variant in Escherichia coli.

BACKGROUND: Streptomyces mobaraenesis transglutaminase (smTG) is widely used to generate protein crosslinking or attachment of small molecules. However, the low thermostability is a main obstacle for smTG application. In addition, it is still hard to achieve the secretory expression of active smTG in E. coli, which benefits the enzyme evolution. In this study, a combined strategy was conducted to improve the thermostability and secretory expression of active smTG in E. coli. RESULTS: First, the thermostable S. mobaraenesis transglutaminase variant S2P-S23V-Y24N-S199A-K294L (TGm1) was intracellularly expressed in pro-enzyme form in E. coli. Fusing the pro-region of Streptomyces hygroscopicus transglutaminase (proH) and TrxA achieved a 9.78 U/mL of intracellular smTG activity, 1.37-fold higher than the TGm1 fused with its native pro-region. After in vitro activation by dispase, the TGm1 with proH yielded FRAPD-TGm1, exhibiting 0.95 â„ƒ and 94.25% increases in melting temperature and half-life at 60 â„ƒ compared to FRAP-TGm1 derived from the expression using its native pro-region, respectively. Second, the TGm1 with proH was co-expressed with transglutaminase activating protease and chaperones (DnaK, DnaJ, and GrpE) in E. coli, achieving 9.51 U/mL of intracellular FRAPD-TGm1 without in vitro activation. Third, the pelB signal peptide was used to mediate the secretory expression of active TGm in E. coli, yielding 0.54 U/mL of the extracellular FRAPD-TGm1. A script was developed to shuffle the codon of pelB and calculate the corresponding mRNA folding energy. A 1.8-fold increase in the extracellular expression of FRAPD-TGm1 was achieved by the Top-9 pelB sequence derived from the coding sequences with the lowest mRNA folding energy. Last, deleting the gene of Braun's lipoprotein further increased the extracellular yield of FRAPD-TGm1 by 31.2%, reached 1.99 U/mL. CONCLUSIONS: The stabilized FRAPD-smTG here could benefit the enzyme application in food and non-food sectors, while the E. coli system that enables secretory expression of active smTG will facilitate the directed evolution for further improved catalytic properties. The combined strategy (N-terminal modification, co-expression with chaperones, mRNA folding energy optimization of signal peptide, and lipoprotein deletion) may also improve the secretory expression of other functional proteins in E. coli.

Harnessing the interface mechanics of hard films and soft substrates for 3D assembly by controlled buckling.

Techniques for forming sophisticated, 3D mesostructures in advanced, functional materials are of rapidly growing interest, owing to their potential uses across a broad range of fundamental and applied areas of application. Recently developed approaches to 3D assembly that rely on controlled buckling mechanics serve as versatile routes to 3D mesostructures in a diverse range of high-quality materials and length scales of relevance for 3D microsystems with unusual function and/or enhanced performance. Nonlinear buckling and delamination behaviors in materials that combine both weak and strong interfaces are foundational to the assembly process, but they can be difficult to control, especially for complex geometries. This paper presents theoretical and experimental studies of the fundamental aspects of adhesion and delamination in this context. By quantifying the effects of various essential parameters on these processes, we establish general design diagrams for different material systems, taking into account 4 dominant delamination states (wrinkling, partial delamination of the weak interface, full delamination of the weak interface, and partial delamination of the strong interface). These diagrams provide guidelines for the selection of engineering parameters that avoid interface-related failure, as demonstrated by a series of examples in 3D helical mesostructures and mesostructures that are reconfigurable based on the control of loading-path trajectories. Three-dimensional micromechanical resonators with frequencies that can be selected between 2 distinct values serve as demonstrative examples.

Intramuscular Near-Infrared Spectroscopy for Muscle Flap Monitoring in a Porcine Model.

BACKGROUND: Current near-infrared spectroscopy (NIRS)-based systems for continuous flap monitoring are limited to flaps which carry a cutaneous paddle. As such, this useful and reliable technology has not previously been applicable to muscle-only free flaps where other modalities with substantial limitations continue to be utilized. METHODS: We present the first NIRS probe which allows continuous monitoring of local tissue oxygen saturation (StO2) directly within the substance of muscle tissue. This probe is flexible, subcentimeter in scale, waterproof, biocompatible, and is fitted with resorbable barbs which facilitate temporary autostabilization followed by easy atraumatic removal. This novel device was compared with a ViOptix T.Ox monitor in a porcine rectus abdominus myocutaneous flap model of arterial and venous occlusions. During these experiments, the T.Ox device was affixed to the skin paddle, while the novel probe was within the muscle component of the same flap. RESULTS: The intramuscular NIRS device and skin-mounted ViOptix T.Ox devices produced very similar StO2 tracings throughout the vascular clamping events, with obvious and parallel changes occurring upon vascular clamping and release. The normalized cross-correlation at zero lag describing correspondence between the novel intramuscular NIRS and T.Ox devices was >0.99. CONCLUSION: This novel intramuscular NIRS probe offers continuous monitoring of oxygen saturation within muscle flaps. This experiment demonstrates the potential suitability of this intramuscular NIRS probe for the task of muscle-only free flap monitoring, where NIRS has not previously been applicable. Testing in the clinical environment is necessary to assess durability and reliability.

A Wireless Near-Infrared Spectroscopy Device for Flap Monitoring: Proof of Concept in a Porcine Musculocutaneous Flap Model.

BACKGROUND: Current near-infrared spectroscopy (NIRS)-based systems for continuous flap monitoring are highly sensitive for detecting malperfusion. However, the clinical utility and user experience are limited by the wired connection between the sensor and bedside console. This wire leads to instability of the flap-sensor interface and may cause false alarms. METHODS: We present a novel wearable wireless NIRS sensor for continuous fasciocutaneous free flap monitoring. This waterproof silicone-encapsulated Bluetooth-enabled device contains two light-emitting diodes and two photodetectors in addition to a battery sufficient for 5 days of uninterrupted function. This novel device was compared with a ViOptix T.Ox monitor in a porcine rectus abdominus myocutaneous flap model of arterial and venous occlusions. RESULTS: Devices were tested in four flaps using three animals. Both devices produced very similar tissue oxygen saturation (StO2) tracings throughout the vascular clamping events, with obvious and parallel changes occurring on arterial clamping, arterial release, venous clamping, and venous release. Small interdevice variations in absolute StO2 value readings and magnitude of change were observed. The normalized cross-correlation at zero lag describing correspondence between the novel NIRS and T.Ox devices was >0.99 in each trial. CONCLUSION: The wireless NIRS flap monitor is capable of detecting StO2 changes resultant from arterial vascular occlusive events. In this porcine flap model, the functionality of this novel sensor closely mirrored that of the T.Ox wired platform. This device is waterproof, highly adhesive, skin conforming, and has sufficient battery life to function for 5 days. Clinical testing is necessary to determine if this wireless functionality translates into fewer false-positive alarms and a better user experience.

Low threshold soliton and a noise-like pulse conversion in an all-polarization-maintaining figure-eight cavity.

We experimentally report a low threshold soliton and a noise-like mode-locked fiber laser using an all-polarization-maintaining figure-eight cavity. We built a bidirectional pump structure without a phase shifter at the beginning of the experiment. The resonator has a high mode-locking threshold of 620 mW. Afterwards, we used a phase shifter in the resonator, and the laser can self-start in a conventional soliton (CS) mode-locked state when pump1 reaches the threshold of only 70 mW. The CS pulse with a duration of 863.8 fs can be observed at 1560 nm. When the two pump powers increase to 350 mW and 50 mW, the conventional soliton can convert to noise-like pulses. The central wavelength and pulse duration of noise-like mode-locked pulse are 1560.4 nm and 417.9 fs, respectively. The laser can realize conversion between ultrafast pulses and high-energy pulses, and have a low threshold that can be used for nonlinear frequency conversion, supercontinuum generation, sensing, etc.

Single-cell RNA-seq analysis reveals the progression of human osteoarthritis.

OBJECTIVES: Understanding the molecular mechanisms underlying human cartilage degeneration and regeneration is helpful for improving therapeutic strategies for treating osteoarthritis (OA). Here, we report the molecular programmes and lineage progression patterns controlling human OA pathogenesis using single-cell RNA sequencing (scRNA-seq). METHODS: We performed unbiased transcriptome-wide scRNA-seq analysis, computational analysis and histological assays on 1464 chondrocytes from 10 patients with OA undergoing knee arthroplasty surgery. We investigated the relationship between transcriptional programmes of the OA landscape and clinical outcome using severity index and correspondence analysis. RESULTS: We identified seven molecularly defined populations of chondrocytes in the human OA cartilage, including three novel phenotypes with distinct functions. We presented gene expression profiles at different OA stages at single-cell resolution. We found a potential transition among proliferative chondrocytes, prehypertrophic chondrocytes and hypertrophic chondrocytes (HTCs) and defined a new subdivision within HTCs. We revealed novel markers for cartilage progenitor cells (CPCs) and demonstrated a relationship between CPCs and fibrocartilage chondrocytes using computational analysis. Notably, we derived predictive targets with respect to clinical outcomes and clarified the role of different cell types for the early diagnosis and treatment of OA. CONCLUSIONS: Our results provide new insights into chondrocyte taxonomy and present potential clues for effective and functional manipulation of human OA cartilage regeneration that could lead to improved health.

MdrL, a major facilitator superfamily efflux pump of Listeria monocytogenes involved in tolerance to benzalkonium chloride.

Efflux pumps are recognized as an important mechanism for decreased susceptibility of benzalkonium chloride (BC) in Listeria monocytogenes. Previous studies showed that the efflux pump MdrL was overexpressed in L. monocytogenes exposed to BC. In the present work, we aimed to clarify the role of MdrL in tolerance to BC and environmental stresses including acid, alkali, osmotic, ethanol, and oxidative stresses, as well as resistance to other antimicrobial agents in L. monocytogenes EGD-e. In addition, regulation of the expression of mdrL by LadR was investigated. Gene deletion mutants were constructed by homologous recombination strategy. For the wild-type and mutant strains, minimum inhibitory concentrations (MICs) of antimicrobial agents were determined by the agar dilution, and the growth and survival analysis were also performed. LadR was expressed and the interaction between LadR and the mdrL promoter was investigated by electrophoretic mobility shift assay (EMSA). Compared to the wild-type strain, the growth of ΔmdrL deletion mutant strain was impaired in the presence of sublethal concentration of BC. Moreover, the mutant showed a lower level of survival than that of the wild-type strain in the presence of lethal concentration of BC. However, the deletion of mdrL had no impact on cefotaxime resistance and ethidium bromide efflux. BC could induce the expression of mdrL in L. monocytogenes and the mdrL expression was regulated by LadR instead of SigmaB. LadR was able to specifically bind to the mdrL promoter. The results showed that efflux pump MdrL was associated with BC tolerance in L. monocytogenes EGD-e. Moreover, our results also provided strong evidence that LadR negatively regulated the expression of mdrL. Since BC is commonly used in the food industry, efflux pump MdrL is beneficial for L. monocytogenes to survive this stress in food processing environments.

miR-223-3p Inhibits Human Osteosarcoma Metastasis and Progression by Directly Targeting CDH6.

Cadherin-6 (CDH6) is aberrantly expressed in cancer and closely associated with tumor progression. However, the functions of CDH6 in human osteosarcoma and the molecular mechanisms underlying CDH6 in osteosarcoma oncogenesis remain poorly understood. In this work, we assessed the role of CDH6 in human osteosarcoma and identified that the expression of CDH6 was closely related with the overall survival and poor prognosis of osteosarcoma patients. MicroRNAs (miRNAs) have been implicated as important epigenetic regulators during the progression of osteosarcoma. Using dual-luciferase reporter assays, we showed that miR-223-3p suppresses CDH6 expression by directly binding to the 3' UTR of CDH6. miR-223-3p overexpression significantly inhibited cell invasion, migration, growth, and proliferation by suppressing the CDH6 expression in vivo and in vitro. Besides, CDH6 overexpression in the miR-223-3p-transfected osteosarcoma cells effectively rescued the inhibition of cell invasion, migration, growth, and proliferation mediated by miR-223-3p. Additionally, Kaplan-Meier analysis suggests that the expression of miR-223-3p predicts favorable clinical outcomes for osteosarcoma patients. Moreover, the expression of miR-223-3p was downregulated in osteosarcoma patients and was negatively associated with the expression of CDH6. Collectively, these data highlight that miR-223-3p/CDH6 axis is an important novel pleiotropic regulator and could early predict the metastatic potential in human osteosarcoma treatments.

High efficiency asymmetric directional coupler for slow light slot photonic crystal waveguides.

An asymmetric directional coupler scheme for the efficient injection of light into slow light slot photonic crystal waveguide modes is proposed and investigated using finite-difference time-domain simulation. Coupling wavelengths can be flexibly controlled by the geometrical parameters of a side-coupled subwavelength corrugated strip waveguide. This approach leads to a ~1dB insertion loss level up to moderately high light group indices (nG≈30) in wavelength ranges of 5-10nm. This work brings new opportunities to inject light into the slow modes of slot photonic crystal waveguides for on-chip communications using hybrid silicon photonics or sensing based on hollow core waveguides.

Regioselective fluorination of allenes enabled by I(I)/I(III) catalysis.

The prominence and versatility of propargylic fluorides in medicinal chemistry, coupled with the potency of F/H and F/OH bioisosterism, has created a powerful impetus to develop efficient methods to facilitate their construction. Motivated by the well-established conversion of propargylic alcohols to allenes, an operationally simple, organocatalysis-based strategy to process these abundant unsaturated precursors to propargylic fluorides would be highly enabling: this would consolidate the bioisosteric relationship that connects propargylic alcohols and fluorides. Herein, we describe a highly regioselective fluorination of unactivated allenes based on I(I)/I(III) catalysis in the presence of an inexpensive HF source that serves a dual role as both nucleophile and Brønsted acid activator. This strategy enables a variety of secondary and tertiary propargylic fluorides to be prepared: these motifs are prevalent across the bioactive small molecule spectrum. Facile product derivatisation, concise synthesis of multi-vicinal fluorinated products together with preliminary validation of enantioselective catalysis are disclosed. The expansive potential of this platform is also demonstrated through the highly regioselective organocatalytic oxidation, chlorination and arylation of allenes. It is envisaged that the transformation will find application in molecular design and accelerate the exploration of organofluorine chemical space.

Epidemic Characteristics and Meteorological Risk Factors of Hemorrhagic Fever With Renal Syndrome in 151 Cities in China From 2015 to 2021: Retrospective Analysis.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) continues to pose a significant public health threat to the population in China. Previous epidemiological evidence indicates that HFRS is climate sensitive and influenced by meteorological factors. However, past studies either focused on too-narrow geographical regions or investigated time periods that were too early. There is an urgent need for a comprehensive analysis to interpret the epidemiological patterns of meteorological factors affecting the incidence of HFRS across diverse climate zones. OBJECTIVE: In this study, we aimed to describe the overall epidemic characteristics of HFRS and explore the linkage between monthly HFRS cases and meteorological factors at different climate levels in China. METHODS: The reported HFRS cases and meteorological data were collected from 151 cities in China during the period from 2015 to 2021. We conducted a 3-stage analysis, adopting a distributed lag nonlinear model and a generalized additive model to estimate the interactions and marginal effects of meteorological factors on HFRS. RESULTS: This study included a total of 63,180 cases of HFRS; the epidemic trends showed seasonal fluctuations, with patterns varying across different climate zones. Temperature had the greatest impact on the incidence of HFRS, with the maximum hysteresis effects being at 1 month (-19 ºC; relative risk [RR] 1.64, 95% CI 1.24-2.15) in the midtemperate zone, 0 months (28 ºC; RR 3.15, 95% CI 2.13-4.65) in the warm-temperate zone, and 0 months (4 ºC; RR 1.72, 95% CI 1.31-2.25) in the subtropical zone. Interactions were discovered between the average temperature, relative humidity, and precipitation in different temperature zones. Moreover, the influence of precipitation and relative humidity on the incidence of HFRS had different characteristics under different temperature layers. The hysteresis effect of meteorological factors did not end after an epidemic season, but gradually weakened in the following 1 or 2 seasons. CONCLUSIONS: Weather variability, especially low temperature, plays an important role in epidemics of HFRS in China. A long hysteresis effect indicates the necessity of continuous intervention following an HFRS epidemic. This finding can help public health departments guide the prevention and control of HFRS and develop strategies to cope with the impacts of climate change in specific regions.

Photosensitization enables Pauson-Khand-type reactions with nitrenes.

The Pauson-Khand reaction has in the past 50 years become one of the most common cycloaddition reactions in chemistry. Coupling two unsaturated bonds with carbon monoxide, the transformation remains limited to CO as a C1 building block. Herein we report analogous cycloaddition reactions with nitrenes as an N1 unit. The reaction of a nonconjugated diene with a nitrene precursor produces bicyclic bioisosteres of common saturated heterocycles such as piperidine, morpholine, and piperazine. Experimental and computational mechanistic studies support relaying of the diradical nature of triplet nitrene into the π-system. We showcase the reaction's utility in late-stage functionalization of drug compounds and discovery of soluble epoxide hydrolase inhibitors.

Bioresorbable shape-adaptive structures for ultrasonic monitoring of deep-tissue homeostasis.

Monitoring homeostasis is an essential aspect of obtaining pathophysiological insights for treating patients. Accurate, timely assessments of homeostatic dysregulation in deep tissues typically require expensive imaging techniques or invasive biopsies. We introduce a bioresorbable shape-adaptive materials structure that enables real-time monitoring of deep-tissue homeostasis using conventional ultrasound instruments. Collections of small bioresorbable metal disks distributed within thin, pH-responsive hydrogels, deployed by surgical implantation or syringe injection, allow ultrasound-based measurements of spatiotemporal changes in pH for early assessments of anastomotic leaks after gastrointestinal surgeries, and their bioresorption after a recovery period eliminates the need for surgical extraction. Demonstrations in small and large animal models illustrate capabilities in monitoring leakage from the small intestine, the stomach, and the pancreas.

Bioresorbable, wireless, passive sensors for continuous pH measurements and early detection of gastric leakage.

Continuous monitoring of biomarkers at locations adjacent to targeted internal organs can provide actionable information about postoperative status beyond conventional diagnostic methods. As an example, changes in pH in the intra-abdominal space after gastric surgeries can serve as direct indicators of potentially life-threatening leakage events, in contrast to symptomatic reactions that may delay treatment. Here, we report a bioresorbable, wireless, passive sensor that addresses this clinical need, designed to locally monitor pH for early detection of gastric leakage. A pH-responsive hydrogel serves as a transducer that couples to a mechanically optimized inductor-capacitor circuit for wireless readout. This platform enables real-time monitoring of pH with fast response time (within 1 hour) over a clinically relevant period (up to 7 days) and timely detection of simulated gastric leaks in animal models. These concepts have broad potential applications for temporary sensing of relevant biomarkers during critical risk periods following diverse types of surgeries.

Slow light in an alternative row of ellipse-hole photonic crystal waveguide.

High normalized delay-bandwidth product (NDBP) and wideband slow light are achieved in an alternative row of ellipse-hole photonic crystal waveguide. Two different criteria of flat ratio are adopted. Under a constant group index criterion, a high NDBP of 0.446 with a group index of 42 and a bandwidth of 16.4 nm are obtained by plane wave expansion calculations, while under a low dispersion criterion, the NDBP, group index, and bandwidth come to 0.352, 41, 13.1 nm, respectively. Low dispersion slow light propagation is numerically demonstrated by studying the relative temporal pulse-width spreading with the two-dimensional finite-difference time-domain method. As a whole, the presented results give indications about the "ultimate" possible improvement of slow light waveguide metrics by using noncircular holes.