Deoxygenation of oximes for the synthesis of pyrrolines via hydroimination cyclization.

Herein, we report the generation of iminyl radicals through photocatalytic deoxygenation of oximes with trivalent phosphine. The hydroimination reaction proceeded via ß-scission of a phosphoranyl radical, followed by 5-exo-trig cyclization of the resulting iminyl radical. This protocol transforms oximes, including alkyl oximes, into a variety of pyrrolines in moderate to good yields. A radical clock experiment confirmed the formation of a cyclic radical and supported our reaction design.

MiR-125 family improves the radiosensitivity of head and neck squamous cell carcinoma.

BACKGROUND: MiRNAs can affect the radiosensitization of head and neck squamous cell carcinoma (HNSCC). We aimed to analyze the function of miR-125 family members in HNSCC using The Cancer Genome Atlas (TCGA) and determine their effect on radiation in laryngeal squamous cell cancer (LSCC). METHODS: First, we systematically analyzed the role of the miR-125 family in HNSCC using the TCGA database and found that miR-125a-5p is associated with radiotherapy. We then performed comprehensive enrichment analysis of miR-125a-5p and predicted target genes. Then, we performed transfection, cell proliferation assays, reverse transcription polymerase chain reaction, apoptosis assays, micronucleus tests, and western blotting on hep-2 cells selected with puromycin. RESULTS: MiR-125 family members exhibited significantly different expression in HNSCC. They were significantly associated with tumor-node-metastasis staging, clinical stages, and histological grades. Radiation therapy had a statistically effect on miR-125 family members, except miR-125a-3p. Moreover, miR-125a-5p was related to overall survival in LSCC. Thus, we predicted 110 target genes and seven hub genes of miR-125a-5p. The proliferation rate of cells transfected with lentivirus vector expressing miR-125a-5p was significantly reduced compared to the other groups. The radiation effect was enhanced in cells transfected with miR-125a-5p. The ratio of apoptotic cells transfected and exposed to X-rays (10 Gy) was distinctly higher than that of the Ad-control group. Western blotting analysis revealed that miR-125a-5p upregulated the apoptotic regulators P53 and rH2AX. Thus, miR-125a-5p may increase radiosensitivity in LSCC via upregulation of pro-apoptotic genes. CONCLUSIONS: MiR-125 family members could be prognostic biomarkers of HNSCC and improve HNSCC sensitivity to radiotherapy by activating P53. Upregulating miR-125a-5p via lentivirus vectors may be a novel strategy to strengthen the effect of radiotherapy on LSCC.

Diastereoselective Radical Aminoacylation of Olefins through N-Heterocyclic Carbene Catalysis.

There have been significant advancements in radical-mediated reactions through covalent-based organocatalysis. Here, we present the generation of iminyl and amidyl radicals via N-heterocyclic carbene (NHC) catalysis, enabling diastereoselective aminoacylation of trisubstituted alkenes. Different from photoredox catalysis, single electron transfer from the deprotonated Breslow intermediate to O-aryl hydroxylamine generates an NHC-bound ketyl radical, which undergoes diastereocontrolled cross-coupling with the prochiral C-centered radical. This operationally simple method provides a straightforward access to a variety of pyrroline and oxazolidinone heterocycles with vicinal stereocenters (77 examples, up to >19:1 d.r.). Electrochemical studies of the acyl thiazolium salts support our reaction design and highlight the reducing ability of Breslow-type derivatives. A detailed computational analysis of this organocatalytic system suggests that radical-radical coupling is the rate-determining step, in which π-π stacking interaction between the radical intermediates subtly controls the diastereoselectivity.

Generation of Oxyphosphonium Ions by Photoredox/Cobaloxime Catalysis for Scalable Amide and Peptide Synthesis in Batch and Continuous-Flow.

Phosphine-mediated deoxygenative nucleophilic substitutions, such as the Mitsunobu reaction, are of great importance in organic synthesis. However, the conventional protocols require stoichiometric oxidants to trigger the formation of the oxyphosphonium intermediates for the subsequent nucleophilic additions. Through dual catalysis of photoredox and cobaloxime, we realized a radical strategy for the catalytic formation of acyloxyphosphonium ions that enables direct amidation. The deoxygenative protocol exhibits a broad scope and has been used in the late-stage amidation of drug molecules. In addition to batch reactions, a continuous-flow reactor was developed, enabling rapid peptide synthesis on gram scale. The successful assembly of a tetrapeptide on the solid support further demonstrated the versatility of this photocatalytic system. Moreover, experimental and computational studies are consistent with the hypothesis of acyloxyphosphonium ions being formed as the key intermediates.

Safety and feasibility of laparoscopic approaches for the management of Mirizzi syndrome: a systematic review.

BACKGROUND: Laparoscopic approaches for the management of Mirizzi syndrome (MS) are controversial and challenging procedures for high conversion rate. This review aims at evaluating their safety and feasibility. METHODS: We reviewed studies related to the laparoscopic approaches for the management of MS with detailed data of articles from January 2009 to December 2019 found in PubMed. RESULTS: From 63 articles, we reviewed 17 articles detailing laparoscopic approaches for MS. There were 857 patients with MS; 432 of which were identified from 73,842 patients underwent cholecystectomy. Laparoscopic approaches were attempted in 440 patients and were successful in 290. The conversion rate was 34.09%. Various methods including laparoscopic cholecystectomy, laparoscopic subtotal cholecystectomy, laparoscopic common bile duct exploration (LCBDE) and (LTCBDE) were performed. The preoperative diagnosis of MS was made in 338 of 500 patients (67.60%). The mean operating time ranged from 49.7 ± 27.5 min to 270.5 ± 65.5 min, and the mean intraoperative bleeding varied from 21.1 ± 15.9 ml to 162.81 ± 40.83 ml. The mean hospital stay varied from 4.5 ± 3.7 to 7.21 ± 1.61 days. Postoperative complications occurred in 27 patients. CONCLUSIONS: Various laparoscopic approaches are safe and feasible for the treatment of MS in the hands of experienced laparoscopic surgeons, especially for type I and II of Csendes classification. Definitive preoperative diagnosis and earlier management are essential.

Density Structure of the Von Kármán Crater in the Northwestern South Pole-Aitken Basin: Initial Subsurface Interpretation of the Chang'E-4 Landing Site Region.

The Von Kármán Crater, within the South Pole-Aitken (SPA) Basin, is the landing site of China's Chang'E-4 mission. To complement the in situ exploration mission and provide initial subsurface interpretation, we applied a 3D density inversion using the Gravity Recovery and Interior Laboratory (GRAIL) gravity data. We constrain our inversion method using known geological and geophysical lunar parameters to reduce the non-uniqueness associated with gravity inversion. The 3D density models reveal vertical and lateral density variations, 2600-3200 kg/m3, assigned to the changing porosity beneath the Von Kármán Crater. We also identify two mass excess anomalies in the crust with a steep density contrast of 150 kg/m3, which were suggested to have been caused by multiple impact cratering. The anomalies from recovered near surface density models, together with the gravity derivative maps extending to the lower crust, are consistent with surface geological manifestation of excavated mantle materials from remote sensing studies. Therefore, we suggest that the density distribution of the Von Kármán Crater indicates multiple episodes of impact cratering that resulted in formation and destruction of ancient craters, with crustal reworking and excavation of mantle materials.

The Asymmetric A³(Aldehyde⁻Alkyne⁻Amine) Coupling: Highly Enantioselective Access to Propargylamines.

The recent developments in asymmetric A³ (aldehyde⁻alkyne⁻amine) coupling has been summarized in this review. Several interesting modifications of the ligands enabled the highly enantioselective synthesis of chiral propargylamines, which are further used in the construction of nitrogen-containing chiral building blocks.

Intramolecular Crossed [2+2] Photocycloaddition through Visible Light-Induced Energy Transfer.

Herein, we present the intramolecular [2+2] cycloadditions of dienones promoted through sensitization, using a polypyridyl iridium(III) catalyst, to form bridged cyclobutanes. In contrast to previous examples of straight [2+2] cycloadditions, these efficient crossed additions were achieved under irradiation with visible light. The reactions delivered desired bridged benzobicycloheptanone products with excellent regioselectivity in high yields (up to 96%). This process is superior to previous syntheses of benzobicyclo[3.1.1]heptanones, which are readily converted to B-norbenzomorphan analogues of biological significance. Electrochemical, computational, and spectroscopic studies substantiated the mechanism of triplet energy transfer and explained the unusual regiocontrol.

Diastereoselectively switchable asymmetric haloaminocyclization for the synthesis of cyclic sulfamates.

An asymmetric synthesis of cyclic sulfamates by catalytic haloaminocyclization of primary sulfamate ester derivatives is described. The remarkable reversal of diastereoselectivity was found to be dependent on the halogen source and the chiral catalyst. By using privileged complexes of N,N'-dioxides with Sc(OTf)3 or Lu(OTf)3 as the catalyst, a variety of enantioenriched syn- and anti-cyclic sulfamates or related trans-aziridines could be obtained in 92-99 % ee and up to 97 % yield.

Chiral bifunctional guanidine-catalyzed enantioselective Aza-Henry reaction of isatin-derived ketimines.

An efficient asymmetric aza-Henry reaction of isatin-derived ketimines has been achieved by using a chiral guanidine-amide organocatalyst. A series of 3-substituted 3-amino-2-oxindoles was obtained with excellent results (up to 99% yield, 94% ee). Other functionalized derivatives were also conveniently transformed. This metal-free system was convenient, practical, and insensitive to air and moisture. On the basis of the crystal structure of the catalyst and NMR spectra analysis, a bifunctional catalytic model was suggested to explain the origin of the asymmetric process.

Enantioselective construction of vicinal tetrasubstituted stereocenters by the mannich reaction of silyl ketene imines with isatin-derived ketimines.

A highly enantioselective Mannich reaction of silyl ketene imines with isatin-derived ketimines has been realized by using a chiral N,N'-dioxide/Zn(II) catalyst. A variety of ß-amino nitriles containing congested vicinal tetrasubstituted stereocenters were obtained with excellent outcomes (up to 98 % yield, >19:1 d.r. and 99 % ee). Based on the experimental investigations, a possible transition state has been proposed to explain the origin of the asymmetric induction.

An Angular Acceleration Based Looming Detector for Moving UAVs.

Visual perception equips unmanned aerial vehicles (UAVs) with increasingly comprehensive and instant environmental perception, rendering it a crucial technology in intelligent UAV obstacle avoidance. However, the rapid movements of UAVs cause significant changes in the field of view, affecting the algorithms' ability to extract the visual features of collisions accurately. As a result, algorithms suffer from a high rate of false alarms and a delay in warning time. During the study of visual field angle curves of different orders, it was found that the peak times of the curves of higher-order information on the angular size of looming objects are linearly related to the time to collision (TTC) and occur before collisions. This discovery implies that encoding higher-order information on the angular size could resolve the issue of response lag. Furthermore, the fact that the image of a looming object adjusts to meet several looming visual cues compared to the background interference implies that integrating various field-of-view characteristics will likely enhance the model's resistance to motion interference. Therefore, this paper presents a concise A-LGMD model for detecting looming objects. The model is based on image angular acceleration and addresses problems related to imprecise feature extraction and insufficient time series modeling to enhance the model's ability to rapidly and precisely detect looming objects during the rapid self-motion of UAVs. The model draws inspiration from the lobula giant movement detector (LGMD), which shows high sensitivity to acceleration information. In the proposed model, higher-order information on the angular size is abstracted by the network and fused with multiple visual field angle characteristics to promote the selective response to looming objects. Experiments carried out on synthetic and real-world datasets reveal that the model can efficiently detect the angular acceleration of an image, filter out insignificant background motion, and provide early warnings. These findings indicate that the model could have significant potential in embedded collision detection systems of micro or small UAVs.

Synthesis of γ-Oxo-phosphonates via N-Heterocyclic Carbene-Catalyzed Acylphosphorylation of Alkenes.

In this study, we present an N-heterocyclic carbene-catalyzed method for the radical acylphosphorylation of alkenes. Electrochemical investigations were employed to identify an appropriate class of oxime phosphonates capable of undergoing a single-electron transfer (SET) with Breslow enolates. The resulting phosphoryl radicals were effectively coupled with diverse styrenes and aldehydes to yield a variety of γ-oxo-phosphonates. Both radical clock experiments and electrochemical studies support our reaction design, and a plausible mechanism for the organocatalytic transformation is proposed.

A Time-Delay Feedback Neural Network for Discriminating Small, Fast-Moving Targets in Complex Dynamic Environments.

Discriminating small moving objects within complex visual environments is a significant challenge for autonomous micro-robots that are generally limited in computational power. By exploiting their highly evolved visual systems, flying insects can effectively detect mates and track prey during rapid pursuits, even though the small targets equate to only a few pixels in their visual field. The high degree of sensitivity to small target movement is supported by a class of specialized neurons called small target motion detectors (STMDs). Existing STMD-based computational models normally comprise four sequentially arranged neural layers interconnected via feedforward loops to extract information on small target motion from raw visual inputs. However, feedback, another important regulatory circuit for motion perception, has not been investigated in the STMD pathway and its functional roles for small target motion detection are not clear. In this article, we propose an STMD-based neural network with feedback connection (feedback STMD), where the network output is temporally delayed, then fed back to the lower layers to mediate neural responses. We compare the properties of the model with and without the time-delay feedback loop and find that it shows a preference for high-velocity objects. Extensive experiments suggest that the feedback STMD achieves superior detection performance for fast-moving small targets, while significantly suppressing background false positive movements which display lower velocities. The proposed feedback model provides an effective solution in robotic visual systems for detecting fast-moving small targets that are always salient and potentially threatening.

Enhancing LGMD's Looming Selectivity for UAV With Spatial-Temporal Distributed Presynaptic Connections.

Collision detection is one of the most challenging tasks for unmanned aerial vehicles (UAVs). This is especially true for small or micro-UAVs due to their limited computational power. In nature, flying insects with compact and simple visual systems demonstrate their remarkable ability to navigate and avoid collision in complex environments. A good example of this is provided by locusts. They can avoid collisions in a dense swarm through the activity of a motion-based visual neuron called the Lobula giant movement detector (LGMD). The defining feature of the LGMD neuron is its preference for looming. As a flying insect's visual neuron, LGMD is considered to be an ideal basis for building UAV's collision detecting system. However, existing LGMD models cannot distinguish looming clearly from other visual cues, such as complex background movements caused by UAV agile flights. To address this issue, we proposed a new model implementing distributed spatial-temporal synaptic interactions, which is inspired by recent findings in locusts' synaptic morphology. We first introduced the locally distributed excitation to enhance the excitation caused by visual motion with preferred velocities. Then, radially extending temporal latency for inhibition is incorporated to compete with the distributed excitation and selectively suppress the nonpreferred visual motions. This spatial-temporal competition between excitation and inhibition in our model is, therefore, tuned to preferred image angular velocity representing looming rather than background movements with these distributed synaptic interactions. Systematic experiments have been conducted to verify the performance of the proposed model for UAV agile flights. The results have demonstrated that this new model enhances the looming selectivity in complex flying scenes considerably and has the potential to be implemented on embedded collision detection systems for small or micro-UAVs.

Attention and Prediction-Guided Motion Detection for Low-Contrast Small Moving Targets.

Small target motion detection within complex natural environments is an extremely challenging task for autonomous robots. Surprisingly, the visual systems of insects have evolved to be highly efficient in detecting mates and tracking prey, even though targets occupy as small as a few degrees of their visual fields. The excellent sensitivity to small target motion relies on a class of specialized neurons, called small target motion detectors (STMDs). However, existing STMD-based models are heavily dependent on visual contrast and perform poorly in complex natural environments, where small targets generally exhibit extremely low contrast against neighboring backgrounds. In this article, we develop an attention-and-prediction-guided visual system to overcome this limitation. The developed visual system comprises three main subsystems, namely: 1) an attention module; 2) an STMD-based neural network; and 3) a prediction module. The attention module searches for potential small targets in the predicted areas of the input image and enhances their contrast against a complex background. The STMD-based neural network receives the contrast-enhanced image and discriminates small moving targets from background false positives. The prediction module foresees future positions of the detected targets and generates a prediction map for the attention module. The three subsystems are connected in a recurrent architecture, allowing information to be processed sequentially to activate specific areas for small target detection. Extensive experiments on synthetic and real-world datasets demonstrate the effectiveness and superiority of the proposed visual system for detecting small, low-contrast moving targets against complex natural environments.

Application of urinary N-acetyl-ß-D-glucosaminidase combined with serum retinol-binding protein in early detection of diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is a microangiopathy of type 2 diabetes mellitus (T2DM), which can damage the kidney through various ways and mechanisms due to the nature of the disease, involving the renal interstitium and glomeruli. However, in the early stage of the disease, patients only showed kidney volume increase and glomerular hyperthyroidism, and typical symptoms that are difficult to arouse individual attention were noticed. AIM: To observe the expression of serum retinol-binding protein (RBP) and urinary N-acetyl-ß-D-glucosaminidase (NAG) in patients with DN, and to analyze their value in disease prediction, so as to provide new targets for early diagnosis and treatment of DN. METHODS: The baseline data of 50 T2DM patients treated in our hospital between January 2021 and December 2022 were retrospectively reviewed and included in group A. The baseline data of 50 patients with type 2 DN admitted to our hospital during the same period were collected and included in group B. The baseline data and serum RBP and urine NAG expression were compared between the two groups to analyze their value in the early prediction of DN. RESULTS: There was no significant difference in age, gender, duration of diabetes, combined hyperlipidemia and combined hypertension between the two groups (P > 0.05); the expression of urinary NAG and serum RBP in group B was higher than that in group A, and the difference was statistically significant (P < 0.05); a multiple logistic regression model was established, and the results showed that urinary NAG and serum RBP were related to the presence or absence of injury in diabetic patients, and overexpression of urinary NAG and serum RBP may be risk factors for renal injury in T2DM patients (OR > 1, P < 0.05); receiver operating curve curve was plotted, and the results showed that the area under the curve of urinary NAG and serum RBP expression alone and in combination for predicting DN was > 0.80, and the predictive value was satisfactory; bivariate Spearman linear correlation analysis showed that there was a positive correlation between urinary NAG and serum RBP expression in patients with DN (r = 0.566, P = 0.000). CONCLUSION: The increased expression of urinary NAG and serum RBP may be the risk factors leading to the progression of T2DM to DN. The possibility of DN can be considered in patients with urinary NAG and serum RBP overexpression by examining the expression of urinary NAG and serum RBP in patients with T2DM in clinical practice.

Photocatalytic Phosphine-Mediated Thioesterification of Carboxylic Acids with Disulfides.

Herein, a practical and effective synthesis of thioesters from readily available carboxylic acids and odorless disulfides was developed under photocatalytic conditions. This approach involves phosphoranyl radical-mediated fragmentation to generate acyl radicals and allows for incorporation of both S atoms of the disulfides into the desired products. In addition to batch reactions, a continuous-flow reactor was employed, enabling rapid thioester synthesis on a gram scale. Preliminary experimental mechanistic studies and the rapid synthesis of dalcetrapib are also demonstrated.

Influence of the built environment on taxi travel demand based on the optimal spatial analysis unit.

When discussing the influence of the built environment on taxi travel demand, few studies have considered the effect of the modifiable areal unit problem (MAUP) or the influence of the "5D" dimensions of the built environment (It refers to the consideration of the built environment from five dimensions of density, diversity, design, destination accessibility and distance to transit.) on taxi travel demand. Moreover, discussion of the nonlinear and linear relationships between taxi demand and environment variables is also lacking. To address these gaps, we constructed a "5D" dimension index system of built environment variables. The influence of the MAUP on the model results was discussed using the optimal parameter-based geographical detector (OPGD) model, and the optimal spatial analysis unit was selected. The OPGD and multiscale geographically weighted regression (MGWR) models were used to reveal the influence of different dimensions of the built environment on taxi travel demand from global and local perspectives, respectively. Finally, the central urban area of Xi'an was analyzed as an example. The results show the following: (1) Most built environment variables are sensitive to the influence of MAUP. (2) It is better to divide the space into regular hexagons than squares, and the optimal spatial analysis unit in this study is a regular hexagon grid with sides of 900m. (3) From a global perspective, the distance to the city center, commercial residence POI density, transportation facility POI density, and population density have the greatest influence on the demand for taxi travel. (4) From a local perspective, the MGWR model considering spatial heterogeneity and scale differences is superior to the GWR model, and the influence of built environment variables exhibited spatial heterogeneity. The proposed optimal spatial analysis unit can provide a basis for taxi demand forecasting and scheduling. This study provides a reference for urban planners and traffic managers to offer optimization strategies related to the built environment, promote healthy development of the taxi industry, and solve the problems of the urban transportation system.