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With the adoption of a ring-strain-release strategy, iridium-catalyzed transannulations with norbornene derivatives are achieved in a diastereospecific and enantioselective manner. The first asymmetric transannulations of 1,2,3-thiadiazoles are reported.

1,2,3-Thiadiazoles serve as masked S-electrophilic thia-1,3-dipoles. Under rhodium/racemic BINAP catalysis, they undergo denitrogenative (3 + 2) umpolung transannulations with aryl isothiocyanates with inverse regioselectivity and excellent stereoselectivity, yielding

A highly diastereoselective and chemoselective (3 + 2) transannulation of 1,2,3-thiadiazoles with cyanoepoxides has been discovered. The use of sterically larger DPEPhos allows the preparation of cis-epoxyl isothiazoles from cis-cyanoepoxides in up to 95% yields and 100 : 0 dr, while the use of sterically smaller DPPF allows the synthesis of trans-products from cis- or trans-cyanoepoxides in up to 95% yields and 100 : 0 dr. Bisphosphines and epoxides play dual roles. Bisphosphines serve not only as ligands, but also as catalysts to catalyze the isomerization of cis-epoxides to trans-isomers. The diastereoselectivity is controlled by the kinetic competition between the direct transannulation of cis-cyanoepoxides and the bisphosphine-catalyzed isomerization of cis-products. The epoxy group's large steric hindrance guarantees excellent chemoselectivity toward the (3 + 2) annulation, and its electron-withdrawing ability significantly improves the reactivity of the adjacent cyano group. To address the controversy over the organorhodium intermediates, we suggest the resonation between Lee's umpolung 1,3-dipoles, Bao's cyclometalated Rh(III) complexes, and our thioacyl-coordinated Rh(I) carbenes. Stereospecific access to isothiazole-fused γ-lactone is also developed.

Percutaneous ablation is a standard therapy for most cases of hepatocellular carcinoma (HCC), which is a general type of primary liver cancer. Magnetic resonance imaging (MRI) offers high-contrast images of soft tissue to monitor the ablation procedure. However, the success of MRI-guided ablation still depends on precise intra-tumor probe placement and skin insertion positioning, both of which require highly experienced operators, and can induce inter-operator variability in ablation results. In this letter, we present a semi-automated robotic system for MRI-guided percutaneous needle procedures. The compact and lightweight design enables the direct fixture of robot on the patient body and simultaneous needle targeting at multiple locations with several robots. Accurate (0.89 ± 0.31 mm) needle navigation is achieved by incorporating soft fluid-driven actuators with feedback control and stiffness modulation capabilities. The 3D location of the needle guide is reconfirmed by wireless MR tracking coils. The performance of the robotic platform, such as stiffness, needle positioning accuracy and frequency response was experimentally evaluated. Negligible interference to MR imaging was also validated by an MR compatibility test.

Background:Tourniquet is currently widely used in total knee arthroplasty to reduce intraoperative blood loss. Academic view of tourniquet application in TKA is now in dispute. Some scholars argue that tourniquet may cause quadriceps injury and bring extra side effects so they oppose the application of tourniquet. Others find that tourniquet application has no significant adverse impact on TKA patients. Regarding its advantages in reducing intraoperative blood loss, they advocate regular application of tourniquet in TKA. Quadriceps injury is considered the main cause of tourniquet side effects. There are now many high-quality trials about tourniquet application in TKA but few of them concentrate on quadriceps morphology and function.Methods:A prospective, single blind, randomized controlled trail will be adopted. The target sample is 130. Patients who meet the eligibility criteria will be randomly allocated to tourniquet group and non-tourniquet group. Primary outcomes are thickness, stiffness and function of quadriceps, which will be evaluated by ultrasound and rehabilitation tests. Secondary outcomes consist of circumference of thigh, VAS score, opioid consumption, knee function score, postoperative satisfaction score, operation time, intraoperative blood loss, perioperative blood loss, blood transfusion rate, D-Dimer, C-reactive protein, and complications. Discussion:This proposed study will contribute to improve evidence of tourniquet application in total knee arthroplasty. This will be a high-quality single blind randomized controlled trial with sufficient sample size and strict study design. It will investigate the effects of tourniquet application especially on the morphology and function of quadriceps in patients undergoing total knee arthroplasty and offer advice for tourniquet application in clinical practice.Trial registration:Chinese clinical trial registry, ChiCTR2000035097. Registered 31 July 2020, http://www.chictr.org.cn/showproj.aspx?proj=57093

To compare the application effects between personal specific instrumentation (PSI) and computer-assisted navigation surgery (CAS) in total knee arthroplasty (TKA).The literature comparing the application effects of PSI and CAS in TKA in recent years was widely consulted, and the difference between PSI-TKA and CAS-TKA in operation time, lower limb alignment, blood loss, and knee function were compared.Compared to CAS-TKA, PSI-TKA simplifies operation procedures and shortens operation time but probably has worse lower limb alignment. It is still controversial in comparison of perioperative blood loss and knee function between two techniques.PSI-TKA and CAS-TKA both have advantages and disadvantages, and their differences need to be confirmed by further high-quality clinical trial.比较个性化截骨导板（personal specific instrumentation，PSI）及计算机辅助导航手术（computer-assisted navigation surgery，CAS）在人工全膝关节置换术（total knee arthroplasty，TKA）中的应用效果。.广泛查阅近年来 PSI 与 CAS 在 TKA 中应用效果比较研究相关文献，分析两种 TKA 辅助技术在手术时间、下肢力线、失血量以及膝关节功能等方面的差异。.与 CAS-TKA 相比，PSI-TKA 简化了手术操作，缩短了手术时间，但对下肢力线的改善可能不及 CAS-TKA；此外，两者在围术期失血量、关节功能等方面的差异仍有争议。.PSI 与 CAS 在 TKA 中的应用各有利弊，其应用效果差异还需要更多高质量临床研究进一步证实。.

Magnetic resonance imaging (MRI) guided intervention has drawn increasing attention over the last decade. It is accredited to the capability of monitoring any physiological change of soft tissue with the high-contrast MR images. This also gives rise to the demand for precise tele-manipulation of interventional instruments. However, there is still lack of choices of MR safe actuators that provide high-fidelity robot manipulation. In this letter, we present a three-cylinder hydraulic motor using rolling-diaphragm-sealed cylinders, which can provide continuous bidirectional rotation with unlimited range. Both kinematics and dynamics models of the presented motor were studied, which facilitate its overall design optimization and position/torque control. Motor performance, such as step response, frequency response, and accuracy, were experimentally evaluated. We also integrate the motor into our catheter robot prototype designed for intra-operative MRI-guided cardiac electrophysiology (EP), which can provide full degree-of-freedom and precise manipulation of a standard EP catheter.

Sulfocoumarins are key structural motifs in several bioactive molecules. Herein, we describe a simple, one-pot procedure for the synthesis of structurally diverse sulfonocoumarin-3-carboxylates by heating 2-hydroxyaryl aldehydes with an active sulfonyl chloride in the presence of pyridine. The process tolerates numerous functional groups including alkoxy, alkyl, halogen, nitro, and even nucleophilic phenolic hydroxy. Additionally, reactions of 2-hydroxyaryl ketones and 2-methylaminoaryl aldehydes give 4-substituted sulfocoumarins and 1-aza-2-sulfocoumarins, respectively. A gram-scale synthesis and further derivatizations are also reported. The ester group is easily removed via ­Happer’s decarboxylation.

A rhodium-catalyzed denitrogenative formal (3 + 3) transannulation of 1,2,3-thiadiazoles with alk-2-enals is achieved, producing 2,3-dihydrothiopyran-4-ones in moderate to excellent yields. An inverse KIE of 0.49 is obtained, suggesting the reversibility of the oxidative addition of thioacyl Rh(I) carbenes to alk-2-enals. The late-stage structural modifications of steroid compounds are realized. Moreover, our studies show that thioacyl carbenes have different reactivities to those of α-oxo and α-imino carbenes, and highlight the importance of heteroatoms in deciding the reactivities of heterovinyl carbenes.

Correction for ‘Catalytic (3 + 2) umpolung annulations of α-thioacyl carbenes with aryl isothiocyanates’ by Ziyang Dong et al., Chem. Commun., 2022, 58, 7980–7983, https://doi.org/10.1039/D2CC02882D.

Siderophore is a chelating iron substance secreted by microorganisms at low intracellular iron concentration. Siderophore can be divided into three categories: catechol salts, hydroxamic salts and carboxylates. The transport of siderophore is regulated by Fur, σ factor and quorum sensing signal. In recent years, siderophore has been used in fields such as oil pollution remediation, heavy metal pollution remediation and pulp biological bleaching, and has received extensive attention. This paper reviews the classification of siderophores and their transport regulation mechanism, and the application of siderophore in environmental pollution control and remediation. Furthermore, we address the application of siderophore in the future.铁载体是微生物在胞内低铁浓度下分泌的螯合铁的物质，可分为儿茶酚盐类、氧肟酸盐类、羧酸盐类三大类。铁载体的转运分别受Fur、σ 因子、群体感应信号这3 种机制调控。近年来铁载体在石油污染修复、重金属污染修复和纸浆生物漂白等领域得到了应用，受到广泛关注。文中综述了铁载体的分类及其转运调控机制，以及铁载体在环境污染治理与修复中的应用，并展望了铁载体今后的应用前景。.

In this letter, we present an intraoperative magnetic resonance imaging (MRI)-guided robot for bilateral stereotactic procedures. Its compact design enables robot's operation within the constrained space of standard imaging head coil. magnetic resonance (MR) safe and high-performance hydraulic transmissions are incorporated. A maximum stiffness coefficient of 24.35 N/mm can be achieved with transmission fluid preloaded at 2 bar. Sufficient targeting accuracy (average within ≤1.73 mm) has been demonstrated in a simulated needle insertion task of deep brain stimulation. A novel MR-based wireless tracking technique is adopted. It is capable of offering real-time and continuous (30-40 Hz) three-dimensional (3-D) localization of robotic instrument under the proper MR tracking sequence. It outperforms the conventional method of using low-contrast passive fiducials that can only be revealed in the MR image domain. Two wireless tracking units/markers are integrated with the robot, which are two miniaturized coil circuits in size of 1.5 × 5 × 0.2 mm 3 , fabricated on flexible thin films. A navigation test was performed under the standard MRI settings in order to visualize the 3-D localization of the robotic instrument. MRI compatibility test was also carried out to prove the minimal interference to MR images of the presented hydraulic robotic platform.

This paper introduces a robotic manipulator to realize robot-assisted intracardiac catheterization in magnetic resonance imaging (MRI) environment. MRI can offer high-resolution images to visualize soft tissue features such as scars or edema. We hypothesize that robotic catheterization, combined with the enhanced monitoring of lesions creation using MRI intraoperatively, will significantly improve the procedural safety, accuracy, and effectiveness. This is designed particularly for cardiac electrophysiological (EP) intervention, which is an effective treatment of arrhythmia. We present the first MR Safe robot for intracardiac EP intervention. The robot actuation features small hysteresis, effective force transmission, and quick response, which has been experimentally verified for its capability to precisely telemanipulate a standard clinically used EP catheter. We also present timely techniques for real-time positional tracking in MRI and intraoperative image registration, which can be integrated with the presented manipulator to im prove the performance of teleoperated robotic catheterization.

Shewanella oneidensis is among the first and the best studied bacteria capable of respiring minerals as terminal electron acceptors (EAs), including a variety of iron ores. This respiration process relies on a large number of c-type cytochromes, which per se are iron-containing proteins. Thus, iron plays an essential and special role in iron respiration of S. oneidensis, prompting extensive investigations into iron physiology. Despite this, we still know surprisingly little about the components and characteristics of iron transport in this bacterium. Here, we report that TonB-dependent receptor PutA (SO_3033) is specific to the siderophore-mediated iron uptake. Although homologs of PutA are abundant, none of them can function as a replacement. In the absence of PutA, S. oneidensis suffers from an iron shortage, which leads to a severe defect in production of cytochrome c. However, proteins requiring other types of cytochromes, such as b and d, do not appear to be significantly impacted. Intriguingly, lactate, but not other carbon sources that are routinely used to support growth, is able to promote iron uptake when PutA is missing. We further show that the lactate-mediated iron import is independent of lactate permeases. Overall, our results suggest that in S. oneidensis the siderophore-dependent pathway plays a key role in iron uptake when iron is limited, but many alternative routes exist.

Introduction Fast Healthcare Interoperability Resources (FHIR), is a standard for exchanging data. It is a common framework that makes it easier to read, write, and transfer medical data, such as patient information securely. SMART is a platform that builds upon the FHIR specification and provides developers with a set of APIs to create applications on top of FHIR. These applications range from retrieving a patient‘s medication history, to evaluating a patient‘s risk of cardiac arrest. The aim of this project was to help individual doctors, small teams of developers, or large medical organisations, who may not be familiar with FHIR, to discover the capabilities of SMART APIs and build applications for this next generation of digital healthcare. Method As part of a joint collaboration between GOSH and UCL computer science (CS), through the industry exchange network programme. CS Students developed a web application using Django, a framework written in Python that employs a model-template-view (MTV) pattern. The client-side templates were built using React. The application’s back-end encapsulates the app’s logic; and interacts with the data persistency layer- a SQLite database. The code snippets are run by querying the SMART STU3 Sandbox. Results A functional web application was developed that collates a catalogue of modular SMART functions that a developer can use to implement in their own application. The platform allows non-coders to explore SMART on FHIR components and develop prototype applications. It has a library of runnable code snippets that can act as a helpful tool and reference when building SMART applications. Conclusion This application supports the development of SMART applications that adhere to FHIR standards in data interoperability, for developers who lack specific knowledge of FHIR standards. Such resources are likely to be of increasing importance as NHS organisations begin to develop customised local programmes using SMART on FHIR.

A rhodium-catalyzed 1,1-hydroacylation of thioacyl carbenes with alkynyl and alkenyl aldehydes and subsequent 6- endo-trig/dig cyclization are realized, giving structurally diverse 4 H-thiopyran-4-ones and 2,3-dihydro-4 H-thiopyran-4-ones in moderate to good yields. The oxidative addition of Rh(I) to aldehydes is proposed to be the turnover-limiting step. Manipulations of estrones demonstrate the applications of our formal (3 + 3) transannulations in the structural modifications of natural products.

Shewanella oneidensis is an extensively studied bacterium capable of respiring minerals, including a variety of iron ores, as terminal electron acceptors (EAs). Although iron plays an essential and special role in iron respiration of S. oneidensis, little has been done to date to investigate the characteristics of iron transport in this bacterium. In this study, we found that all proteins encoded by the pub-putA-putB cluster for putrebactin (S. oneidensis native siderophore) synthesis (PubABC), recognition-transport of Fe3+-putrebactin across the outer membrane (PutA), and reduction of ferric putrebactin (PutB) are essential to putrebactin-mediated iron uptake. Although homologs of PutA are many, none can function as its replacement, but some are able to work with other bacterial siderophores. We then showed that Fe2+-specific Feo is the other primary iron uptake system, based on the synthetical lethal phenotype resulting from the loss of both iron uptake routes. The role of the Feo system in iron uptake appears to be more critical, as growth is significantly impaired by the absence of the system but not of putrebactin. Furthermore, we demonstrate that hydroxyl acids, especially α-types such as lactate, promote iron uptake in a Feo-dependent manner. Overall, our findings underscore the importance of the ferrous iron uptake system in metal-reducing bacteria, providing an insight into iron homeostasis by linking these two biological processes. IMPORTANCES. oneidensis is among the first- and the best-studied metal-reducing bacteria, with great potential in bioremediation and biotechnology. However, many questions regarding mechanisms closely associated with those applications, such as iron homeostasis, including iron uptake, export, and regulation, remain to be addressed. Here we show that Feo is a primary player in iron uptake in addition to the siderophore-dependent route. The investigation also resolved a few puzzles regarding the unexpected phenotypes of the putA mutant and lactate-dependent iron uptake. By elucidating the physiological roles of these two important iron uptake systems, this work revealed the breadth of the impacts of iron uptake systems on the biological processes.

Iron, a major protein cofactor, is essential for most organisms but can simultaneously be toxic. Iron homeostasis thus has to be effectively maintained under a range of iron regimes. This may be particularly true with Shewanella oneidensis , a representative of dissimilatory metal-reducing bacteria (DMRB), which are capable of respiring a variety of chemicals as electron acceptors (EAs), including iron ores. Although iron respiration and its regulation have been extensively studied in this bacterium, how iron homeostasis is maintained remains largely unknown. Here, we report that the loss of the iron homeostasis master regulator Fur negatively affects the respiration of all EAs tested. This defect appears mainly to be a result of reduced cytochrome c (cyt c ) production, despite a decrease in the expression of reductases that are under the direct control of Fur. We also show that S. oneidensis Fur interacts with canonical Fur box motifs in F-F-x-R configuration rather than the palindromic motif proposed before. The fur mutant has lowered total iron and increased free iron contents. Under iron-rich conditions, overproduction of the major iron storage protein Bfr elevates the total iron levels of the fur mutant over those of the wild-type but does not affect free iron levels. Intriguingly, such an operation only marginally improves cyt c production by affecting heme b biosynthesis. It is established that iron dictates heme b /cyt c biosynthesis in S. oneidensis fur + strains, but the fur mutation annuls the dependence of heme b /cyt c biosynthesis on iron. Overall, our results suggest that Fur has a profound impact on the iron homeostasis of S. oneidensis , through which many physiological processes, especially respiration, are transformed. IMPORTANCE Iron reduction is a signature of S. oneidensis , and this process relies on a large number of type c cytochromes, which per se are iron-containing proteins. Thus, iron plays an essential and special role in iron respiration, but to date, the nature of iron metabolism and regulation of the bacterium remains largely unknown. In this study, we investigated impacts of Fur, the master regulator of iron homeostasis, on respiration. The loss of Fur causes a general defect in respiration, a result of impaired cyt c production rather than specific regulation. Additionally, the fur mutant is unresponsive to iron, resulting in imbalanced iron homeostasis and dissociation between iron and cyt c production. These findings provide important insights into the iron biology of DMRB.

In cardiac electrophysiology, a long and flexible catheter is delivered to a cardiac chamber for the treatment of arrhythmias. Although several robot-assisted platforms have been commercialized, the disorientation in tele-operation is still not well solved. We propose a validation platform for robot-assisted cardiac EP catheterization, integrating a customized MR Safe robot, a standard clinically used EP catheter, and a human–robot interface. Both model-based and model-free control methods are implemented in the platform for quantitative evaluation and comparison. The model-based and model-free control methods were validated by subject test (ten participants), in which the subjects have to perform a simulated radiofrequency ablation task using both methods. A virtual endoscopic view of the catheter is also provided to enhance hand-to-eye coordination. Assessment indices for targeting accuracy and efficiency were acquired for the evaluation. (1) Accuracy: The average distance measured from catheter tip to the closest lesion target during ablation of model-free method was 19.1% shorter than that of model-based control. (2) Efficiency: The model-free control reduced the total missed targets by 35.8% and the maximum continuously missed targets by 46.2%, both indices corresponded to a low p value ( $$\le 0.05$$ ). The model-free method performed better in terms of both accuracy and efficiency, indicating the model-free control could adapt to soft interaction with environment, as compared with the model-based control that does not consider contacts.

Iron, a major protein cofactor, is essential for most organisms but can simultaneously be toxic. Iron homeostasis thus has to be effectively maintained under a range of iron regimes. This may be particularly true with Shewanella oneidensis, a representative of dissimilatory metal-reducing bacteria (DMRB), which are capable of respiring a variety of chemicals as electron acceptors (EAs), including iron ores. Although iron respiration and its regulation have been extensively studied in this bacterium, how iron homeostasis is maintained remains largely unknown. Here, we report that the loss of the iron homeostasis master regulator Fur negatively affects the respiration of all EAs tested. This defect appears mainly to be a result of reduced cytochrome c (cyt c) production, despite a decrease in the expression of reductases that are under the direct control of Fur. We also show that S. oneidensis Fur interacts with canonical Fur box motifs in F-F-x-R configuration rather than the palindromic motif proposed before. The fur mutant has lowered total iron and increased free iron contents. Under iron-rich conditions, overproduction of the major iron storage protein Bfr elevates the total iron levels of the fur mutant over those of the wild-type but does not affect free iron levels. Intriguingly, such an operation only marginally improves cyt c production by affecting heme b biosynthesis. It is established that iron dictates heme b/cyt c biosynthesis in S. oneidensis fur+ strains, but the fur mutation annuls the dependence of heme b/cyt c biosynthesis on iron. Overall, our results suggest that Fur has a profound impact on the iron homeostasis of S. oneidensis, through which many physiological processes, especially respiration, are transformed.

Objective A major challenge in radiofrequency catheter ablation procedure (RFCA) is the voltage and activation mapping of the endocardium, given a limited mapping time. By learning from expert interventional electrophysiologists (operator), while also making use of an active-learning framework, guidance on performing car- diac voltage mapping can be provided to novice operators, or even directly to catheter robots. Methods A Learning from Demonstration (LfD) framework, based upon previous car- diac mapping procedures performed by an expert operator, in conjunction with Gaus- sian process (GP) model-based active learning, was developed to efficiently perform voltage mapping over right ventricles (RV). The GP model was used to output the next best mapping point, while getting updated towards the underlying voltage data pattern, as more mapping points are taken. A regularized particle filter was used to keep track of the kernel hyperparameter used by GP. The travel cost of the catheter tip was incorporated to produce time-efficient mapping sequences. Results The proposed strategy was validated on a simulated 2D grid mapping task, with leave-one-out experiments on 25 retrospective datasets, in an RV phantom using the Stereotaxis Niobe R © remote magnetic navigation system, and on a tele-operated catheter robot. In comparison to an existing geometry-based method, regression error was reduced, and was minimized at a faster rate over retrospective procedure data. Conclusion A new method of catheter mapping guidance has been proposed based on LfD and active learning. The proposed method provides real-time guidance for the procedure, as well as a live evaluation of mapping sufficiency.

Objective A major challenge in radiofrequency catheter ablation procedures is the voltage and activation mapping of the endocardium, given a limited mapping time. By learning from expert interventional electrophysiologists (operators), while also making use of an active-learning framework, guidance on performing cardiac voltage mapping can be provided to novice operators or even directly to catheter robots. Methods A learning from demonstration (LfD) framework, based upon previous cardiac mapping procedures performed by an expert operator, in conjunction with Gaussian process (GP) model-based active learning, was developed to efficiently perform voltage mapping over right ventricles (RV). The GP model was used to output the next best mapping point, while getting updated towards the underlying voltage data pattern as more mapping points are taken. A regularized particle filter was used to keep track of the kernel hyperparameter used by GP. The travel cost of the catheter tip was incorporated to produce time-efficient mapping sequences. Results The proposed strategy was validated on a simulated 2D grid mapping task, with leave-one-out experiments on 25 retrospective datasets, in an RV phantom using the Stereotaxis Niobe® remote magnetic navigation system, and on a tele-operated catheter robot. In comparison with an existing geometry-based method, regression error was reduced and was minimized at a faster rate over retrospective procedure data. Conclusion A new method of catheter mapping guidance has been proposed based on LfD and active learning. The proposed method provides real-time guidance for the procedure, as well as a live evaluation of mapping sufficiency.