A mitochondria-specific NIR fluorescence probe for dual-detection of sulfur dioxide and viscosity in living cells and mice.

The level of sulfur dioxide (SO2) and viscosity in mitochondria play vital roles in various physiological and pathological processes. Abnormalities in mitochondrial SO2 and viscosity are closely associated with numerous biological diseases. It is of great significance to develop novel fluorescence probes for simultaneous detection of SO2 and viscosity within mitochondria. Herein, we have developed a water-soluble, mitochondrial-targeted and near-infrared fluorescent probe, CMBT, for the simultaneous detection of SO2 and viscosity. The probe CMBT incorporates benzothiazolium salt as a mitochondrial targeting moiety and 7-diethylaminocoumarin as a rotor for viscosity detection, respectively. Based on the prompt reaction between nucleophilic HSO3-/SO32- and the backbone of the benzothiazolium salt derivative, probe CMBT displayed high sensitivity and selectivity toward SO2 with a limit of detection as low as 0.17 µM. As viscosity increased, the twisted intramolecular charge transfer (TICT) process was restricted, resulting in fluorescence emission enhancement at 690 nm. Moreover, probe CMBT demonstrated exceptional mitochondrial targeting ability and was successfully employed to image variations of SO2 and viscosity in living cells and mice. The work highlights the great potential of the probe as a convenient tool for revealing the relationship between SO2 and viscosity in biological systems.

First-principles studies on the process of electron transfer between hydrophobic liquids and water.

Using the density functional theory, we conducted a study on the electrification upon contact between hydrophobic liquid molecules and water molecules, revealing localized characteristics of contact-electrification. These "localized features" refer to the specific microscale characteristics where electron transfer predominantly occurs at the contact regions, influenced by factors such as atomic distances and molecular orientations. Although the electrostatic potential and the highest occupied molecular orbital-lowest unoccupied molecular orbital gap offer substantial predictive insights for electron transfer across polymer interfaces, they fall short in capturing the complexities associated with the interaction between hydrophobic liquids and water molecules. The electronegativity of elements at the interface and the localization of molecular orbitals play a decisive role in electron transfer. Simultaneously, for liquid molecules with irregular structures, there is no correlation between the "contact area" and the amount of electron transfer. The "contact area" refers to the surface region where two different liquid molecules come into close proximity. It is defined by the surface area of atoms with interatomic distances smaller than the van der Waals radius. This study challenges traditional assumptions about contact-electrification, particularly in liquid-liquid interfaces, providing new insights into the localized nature of this phenomenon.

Acoustically Enhanced Triboelectric Stethoscope for Ultrasensitive Cardiac Sounds Sensing and Disease Diagnosis.

Electronic stethoscope used to detect cardiac sounds that contain essential clinical information is a primary tool for diagnosis of various cardiac disorders. However, the linear electromechanical constitutive relation makes conventional piezoelectric sensors rather ineffective to detect low-intensity, low-frequency heart acoustic signal without the assistance of complex filtering and amplification circuits. Herein, it is found that triboelectric sensor features superior advantages over piezoelectric one for microquantity sensing originated from the fast saturated constitutive characteristic. As a result, the triboelectric sensor shows ultrahigh sensitivity (1215 mV Pa-1) than the piezoelectric counterpart (21 mV Pa-1) in the sound pressure range of 50-80 dB under the same testing condition. By designing a trumpet-shaped auscultatory cavity with a power function cross-section to achieve acoustic energy converging and impedance matching, triboelectric stethoscope delivers 36 dB signal-to-noise ratio for human test (2.3 times of that for piezoelectric one). Further combining with machine learning, five cardiac states can be diagnosed at 97% accuracy. In general, the triboelectric sensor is distinctly unique in basic mechanism, provides a novel design concept for sensing micromechanical quantities, and presents significant potential for application in cardiac sounds sensing and disease diagnosis.

Reduction of precious metal ions in aqueous solutions by contact-electro-catalysis.

Precious metals are core assets for the development of modern technologies in various fields. Their scarcity poses the question of their cost, life cycle and reuse. Recently, an emerging catalysis employing contact-electrification (CE) at water-solid interfaces to drive redox reaction, called contact-electro-catalysis (CEC), has been used to develop metal free mechano-catalytic methods to efficiently degrade refractory organic compounds, produce hydrogen peroxide, or leach metals from spent Li-Ion batteries. Here, we show ultrasonic CEC can successfully drive the reduction of Ag(ac), Rh3+, [PtCl4]2-, Ag+, Hg2+, Pd2+, [AuCl4]-, and Ir3+, in both anaerobic and aerobic conditions. The effect of oxygen on the reaction is studied by electron paramagnetic resonance (EPR) spectroscopy and ab-initio simulation. Combining measurements of charge transfers during water-solid CE, EPR spectroscopy and gold extraction experiments help show the link between CE and CEC. What's more, this method based on water-solid CE is capable of extracting gold from synthetic solutions with concentrations ranging from as low as 0.196 ppm up to 196 ppm, reaching in 3 h extraction capacities ranging from 0.756 to 722.5 mg g-1 in 3 h. Finally, we showed CEC is employed to design a metal-free, selective, and recyclable catalytic gold extraction methods from e-waste aqueous leachates.

Spontaneously established reverse electric field to enhance the performance of triboelectric nanogenerators via improving Coulombic efficiency.

Mechanical energy harvesting using triboelectric nanogenerators is a highly desirable and sustainable method for the reliable power supply of widely distributed electronics in the new era; however, its practical viability is seriously challenged by the limited performance because of the inevitable side-discharge and low Coulombic-efficiency issues arising from electrostatic breakdown. Here, we report an important progress on these fundamental problems that the spontaneously established reverse electric field between the electrode and triboelectric layer can restrict the side-discharge problem in triboelectric nanogenerators. The demonstration employed by direct-current triboelectric nanogenerators leads to a high Coulombic efficiency (increased from 28.2% to 94.8%) and substantial enhancement of output power. More importantly, we demonstrate this strategy is universal for other mode triboelectric nanogenerators, and a record-high average power density of 6.15 W m-2 Hz-1 is realized. Furthermore, Coulombic efficiency is verified as a new figure-of-merit to quantitatively evaluate the practical performance of triboelectric nanogenerators.

Novel Quantitative Contrast Sensitivity Function Enhances the Prediction of Treatment Outcome and Recurrence in Amblyopia.

Purpose: Although effective amblyopia treatments are available, treatment outcome is unpredictable, and the condition recurs in up to 25% of the patients. We aimed to evaluate whether a large-scale quantitative contrast sensitivity function (CSF) data source, coupled with machine learning (ML) algorithms, can predict amblyopia treatment response and recurrence in individuals. Methods: Visual function measures from traditional chart vision acuity (VA) and novel CSF assessments were used as the main predictive variables in the models. Information from 58 potential predictors was extracted to predict treatment response and recurrence. Six ML methods were applied to construct models. The SHapley Additive exPlanations was used to explain the predictions. Results: A total of 2559 consecutive records of 643 patients with amblyopia were eligible for modeling. Combining variables from VA and CSF assessments gave the highest accuracy for treatment response prediction, with the area under the receiver operating characteristic curve (AUC) of 0.863 and 0.815 for outcome predictions after 3 and 6 months, respectively. Variables from the VA assessment alone predicted the treatment response, with AUC values of 0.723 and 0.675 after 3 and 6 months, respectively. Variables from the CSF assessment gave rise to an AUC of 0.909 for recurrence prediction compared to 0.539 for VA assessment alone, and adding VA variables did not improve predictive performance. The interocular differences in CSF features are significant contributors to recurrence risk. Conclusions: Our models showed CSF data could enhance treatment response prediction and accurately predict amblyopia recurrence, which has the potential to guide amblyopia management by enabling patient-tailored decision making.

[UPLC-QE-Orbitrap-MS combined with network pharmacology to explore differential components and mechanisms of raw and scorched rhubarb for treatment of ulcerative colitis].

This study compared the therapeutic difference effects of the raw and scorched rhubarb for the treatment of ulcerative colitis(UC) and explored their difference in chemical components and mechanisms by using ultra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UPLC-QE-Orbitrap-MS) and network pharmacology. The UC therapeutic effects of Shaoyao Decoction with the raw rhubarb or the scorched rhubarb were evaluated by dextran sulfate sodium(DSS)-induced mouse model. The results showed that Shaoyao Decoction with either the raw rhubarb or the scorched rhubarb could relieve the UC symptoms of mice to different extents, while the scorched rhubarb-based formula showed advantages in reducing hemorrhagic diarrhea and inflammation levels. UPLC-QE-Orbitrap-MS was used to identify a total of 78 small molecules in the water decoction of the raw and scorched rhubarb. Multivariate statistical methods were used to screen components increasing significantly after the scorching process. The seven compounds included five free anthraquinones, gallic acid, and 5-hydroxymethylfurfural(HMF). Meanwhile, the nine compounds decreasing scorching were mainly combined anthraquinones and catechins-related compounds. Network pharmacology and molecular docking suggested that free anthraquinones, gallic acid, and 5-HMF may act on core targets such as B-cell lymphoma-2(BCL2), epidermal growth factor receptor(EGFR), tumor necrosis factor(TNF), and caspase-3(CASP3) and influence the signaling pathways such as phosphoinositide-3-kinase/protein kinase B(PI3K/Akt), hypoxia inducible factor-1(HIF-1), TNF, and mitogen-activated protein kinase(MAPK), so as to regulate the inflammation response, oxidative stress, and cell apoptosis to relieve UC symptoms. This study compared the therapeutic effects and chemical components of the raw and scorched rhubarb, providing the clinical reference for using rhubarb to treat UC.

Enabling identification of component processes in perceptual learning with nonparametric hierarchical Bayesian modeling.

Perceptual learning is a multifaceted process, encompassing general learning, between-session forgetting or consolidation, and within-session fast relearning and deterioration. The learning curve constructed from threshold estimates in blocks or sessions, based on tens or hundreds of trials, may obscure component processes; high temporal resolution is necessary. We developed two nonparametric inference procedures: a Bayesian inference procedure (BIP) to estimate the posterior distribution of contrast threshold in each learning block for each learner independently and a hierarchical Bayesian model (HBM) that computes the joint posterior distribution of contrast threshold across all learning blocks at the population, subject, and test levels via the covariance of contrast thresholds across blocks. We applied the procedures to the data from two studies that investigated the interaction between feedback and training accuracy in Gabor orientation identification over 1920 trials across six sessions and estimated learning curve with block sizes L = 10, 20, 40, 80, 160, and 320 trials. The HBM generated significantly better fits to the data, smaller standard deviations, and more precise estimates, compared to the BIP across all block sizes. In addition, the HBM generated unbiased estimates, whereas the BIP only generated unbiased estimates with large block sizes but exhibited increased bias with small block sizes. With L = 10, 20, and 40, we were able to consistently identify general learning, between-session forgetting, and rapid relearning and adaptation within sessions. The nonparametric HBM provides a general framework for fine-grained assessment of the learning curve and enables identification of component processes in perceptual learning.

Unique aminothiazolyl coumarins as potential DNA and membrane disruptors towards Enterococcus faecalis.

Aminothiazolyl coumarins as potentially new antimicrobial agents were designed and synthesized in an effort to overcome drug resistance. Biological activity assay revealed that some target compounds exhibited significantly inhibitory efficiencies toward bacteria and fungi including drug-resistant pathogens. Especially, aminothiazolyl 7-propyl coumarin 8b and 4-dichlorobenzyl derivative 11b exhibited bactericidal potential (MBC/MIC = 2) toward clinically drug-resistant Enterococcus faecalis with low cytotoxicity to human lung adenocarcinoma A549 cells, rapidly bactericidal effects and no obvious bacterial resistance development against E. faecalis. The preliminary antibacterial action mechanism studies suggested that compound 11b was able to disturb E. faecalis membrane effectively, and interact with bacterial DNA isolated from resistant E. faecalis through noncovalent bonds to cleave DNA, thus inhibiting the growth of E. faecalis strain. Further molecular modeling indicated that compounds 8b and 11b could bind with SER-1084 and ASP-1083 residues of gyrase-DNA complex through hydrogen bonds and hydrophobic interactions. Moreover, compound 11b showed low hemolysis and in vivo toxicity. These findings of aminothiazolyl coumarins as unique structural scaffolds might hold a large promise for the treatments of drug-resistant bacterial infection.

Transcriptome dynamics of the BHK21 cell line in response to human coronavirus OC43 infection.

The progress of viral infection involves numerous transcriptional regulatory events. The identification of the newly synthesized transcripts helps us to understand the replication mechanisms and pathogenesis of the virus. Here, we utilized a time-resolved technique called metabolic RNA labeling approach called thiol(SH)-linked alkylation for the metabolic sequencing of RNA (SLAM-seq) to differentially elucidate the levels of steady-state and newly synthesized RNAs of BHK21 cell line in response to human coronavirus OC43 (HCoV-OC43) infection. Our results showed that the Wnt/ß-catenin signaling pathway was significantly enriched with the newly synthesized transcripts of BHK21 cell line in response to HCoV-OC43 infection. Moreover, inhibition of the Wnt pathway promoted viral replication in the early stage of infection, but inhibited it in the later stage of infection. Furthermore, remdesivir inhibits the upregulation of the Wnt/ß-catenin signaling pathway induced by early infection with HCoV-OC43. Collectively, our study showed the diverse roles of Wnt/ß-catenin pathway at different stages of HCoV-OC43 infection, suggesting a potential target for the antiviral treatment. In addition, although infection with HCoV-OC43 induces cytopathic effects in BHK21 cells, inhibiting apoptosis does not affect the intracellular replication of the virus. Monitoring newly synthesized RNA based on such time-resolved approach is a highly promising method for studying the mechanism of viral infections.

A Human Friendly Self-Assembled Triboelectric Sensor for Multifunctional Tactile Sensing.

Obtaining bioenergy from human movement is not only a prospective complementation to electrochemical power supply such as batteries in portable electronics but also a decipherable process for developing self-powered sensors that can simultaneously monitor the physiological movement. In this study, a low-cost, robust, and environmentally friendly triboelectric nanogenerator (TENG) was prepared with enhanced mechanical stability and tunneling conductivity on the base of cotton fabric. The as-designed TENG may produce energy sustainably by physical movements, and it can yield an amazing 417 V open-circuit voltage, 11.7 µA short-circuit current, and 237.60 mW/m2 excellent power density, showcasing its potential for efficient energy conversion in the single-electrode mode. Besides, such a design also shows real-time tactile perception ability toward human physiological signal and body motion where intelligent application of these environmental benign TENGs in sports and writing training were demonstrated, thus providing vital instruction for the creation of versatile and sustainable TENGs in the Internet of Things era.

Miniaturized and High Volumetric Energy Density Power Supply Device Based on a Broad-Frequency Vibration Driven Triboelectric Nanogenerator.

The widespread vibration is one of the most promising energy sources for IoT and small sensors, and broad-frequency vibration energy harvesting is important. Triboelectric nanogenerators (TENGs) can convert vibration energy into electrical energy through triboelectricity and electrostatic induction, providing an effective solution to the collection of broad-frequency vibration energy. Also, the power supply in constrained and compact spaces has been a long-standing challenge. Here, a miniaturized power supply (MPS) based on a broad-frequency vibration-driven triboelectric nanogenerator (TENG) is developed. The size of the MPS is 38 mm × 26 mm × 20 mm, which can adapt to most space-limited environments. The TENG device is optimized through theoretical mechanical modeling for the external stimuli, it can efficiently harvest vibrational energy in the frequency range of 1-100 Hz and has a high output power density of 134.11 W/cm3. The developed device demonstrates its practical application potential in powering small electronics like LEDs, watches, and timers.

Self-Powered Traffic Lights Through Wind Energy Harvesting Based on High-Performance Fur-Brush Dish Triboelectric Nanogenerators.

Traffic lights play vital roles in urban traffic management systems, providing clear directional guidance for vehicles and pedestrians while ensuring traffic safety. However, the vast quantity of traffic lights widely distributed in the transportation system aggravates energy consumption. Here, a self-powered traffic light system is proposed through wind energy harvesting based on a high-performance fur-brush dish triboelectric nanogenerator (FD-TENG). The FD-TENG harvests wind energy to power the traffic light system continuously without needing an external power supply. Natural rabbit furs are applied to dish structures, due to their outstanding characteristics of shallow wear, high performance, and resistance to humidity. Also, the grid pattern of the dish structure significantly impacts the TENG outputs. Additionally, the internal electric field and the influences of mechanical and structural parameters on the outputs are analyzed by finite element simulations. After optimization, the FD-TENG can achieve a peak power density of 3.275 W m-3. The portable and miniature features of FD-TENG make it suitable for other natural environment systems such as forests, oceans, and mountains, besides the traffic light systems. This study presents a viable strategy for self-powered traffic lights, establishing a basis for efficient environmental energy harvesting toward big data and Internet of Things applications.

Wind Aggregation Enhanced Triboelectric-Electromagnetic Hybrid Generator with Slit Effect.

It is of great significance to establish a low-cost, high-efficiency, self-powered micrometeorological monitoring system for agriculture, animal husbandry, and transportation. However, each additional detection element in the meteorological monitoring system increases the power consumption of the whole system by about 0.7 W. As a renewable energy technology, a triboelectric nanogenerator has the advantages of low price and self-powered sensing. To reduce the power consumption of the micrometeorological monitoring system, this work introduces an innovative solution: the wind-gathering enhanced triboelectric-electromagnetic hybrid generator (WGE-TEHG). Coupling the thin-film vibrating triboelectric nanogenerator (TENG) and electromagnetic generator (EMG), the TENG is used to monitor wind direction and the EMG is used to monitor wind speed and provide energy needed by the system. In particular, the TENG can be used as a self-powered sensor to reduce the power consumption of the sensing system. Besides, the TENG is used to produce slit effect to enhance the output performance of EMG. The experimental results show that the WGE-TEHG can build a self-powered natural environment micrometeorological sensing system. It can monitor the wind direction, wind speed, temperature, and relative humidity. This research has great application value for the self-powered sensing implementation of a hybrid TENG and EMG.

Self-Powered Agricultural Product Preservation and Wireless Monitoring Based on Dual-Functional Triboelectric Nanogenerator.

The global annual vegetable and fruit waste accounts for more than one-fifth of food waste, mainly due to deterioration. In addition, agricultural product spoilage can produce foodborne illnesses and threaten public health. Eco-friendly preservation technologies for extending the shelf life of agricultural products are of great significance to socio-economic development. Here, we report a dual-functional TENG (DF-TENG) that can simultaneously prolong the storage period of vegetables and realize wireless storage condition monitoring by harvesting the rotational energy. Under the illumination of the self-powered high-voltage electric field, the deterioration of vegetables can be effectively slowed down. It can not only decrease the respiration rate and weight loss of pakchoi but also increase the chlorophyll levels (∼33.1%) and superoxide dismutase activity (∼11.1%) after preservation for 4 days. Meanwhile, by harvesting the rotational energy, the DF-TENG can be used to drive wireless sensors for monitoring the storage conditions and location information of vegetables during transportation in real time. This work provides a new direction for self-powered systems in cost-effective and eco-friendly agricultural product preservation, which may have far-reaching significance to the construction of a sustainable society for reducing food waste.

Anti-inflammatory and protective effects of Pimpinella candolleana on ulcerative colitis in rats: a comprehensive study of quality, chemical composition, and molecular mechanisms.

Introduction: P. candolleana Wight et Arn. Is a traditional Chinese herbal medicine used by the Gelao nationality in southwest China, has been historically applied to treat various gastrointestinal disorders. Despite its traditional usage, scientific evidence elucidating its efficacy and mechanisms in treating ulcerative colitis (UC) remains sparse. This study aimed to determine the quality and chemical composition of Pimpinella candolleana and to identify its potential therapeutic targets and mechanisms in acetic acid-induced ulcerative colitis (UC) rats through integrated approaches. Methods: Morphological and microscopic characteristics, thin layer chromatography (TLC) identification, and quantitative analysis of P. candolleana were performed. UPLC-Q-TOF-MS, network pharmacology, and molecular docking were used to identify its chemical composition and predict its related targets in UC. Furthermore, a rat model was established to evaluate the therapeutic effect and potential mechanism of P. candolleana on UC. Results: Microscopic identification revealed irregular and radial arrangement of the xylem in P. candolleana, with a light green cross-section and large medullary cells. UPLC-Q-TOF-MS analysis detected and analyzed 570 metabolites, including flavonoids, coumarins, and terpenoids. Network pharmacology identified 12 effective components and 176 target genes, with 96 common targets for P. candolleana-UC, including quercetin, luteolin, and nobiletin as key anti-inflammatory components. GO and KEGG revealed the potential involvement of their targets in RELA, JUN, TNF, IKBKB, PTGS2, and CHUK, with action pathways such as PI3K-Akt, TNF, IL-17, and apoptosis. Molecular docking demonstrated strong affinity and binding between these key components (quercetin, luteolin, and nobiletin) and the key targets of the pathway, including JUN and TNF. Treatment with P. candolleana improved body weight loss, the disease activity index, and colonic histological damage in UC rats. Pimpinella candolleana also modulated the levels of IL-2 and IL-6 in UC rats, reduced the expression of pro-inflammatory cytokines such as IL-6, MAPK8, TNF-α, CHUK, and IKBKB mRNA, and decreased the expression of TNF, IKBKB, JUN, and CHUK proteins in the colon of UC rats, thereby reducing inflammation and alleviating UC symptoms. Conclusion: P. candolleana exerts its protective effect on UC by reducing the expression of proinflammatory cytokines and inhibiting inflammation, providing scientific evidence for its traditional use in treating gastrointestinal diseases. This study highlights the potential of P. candolleana as a natural therapeutic agent for UC and contributes to the development of novel medicines for UC treatment.

Subdural effusion associated with COVID-19 encephalopathy: A case report.

BACKGROUND: The precise mechanism by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacts the central nervous system remains unclear, with manifestations spanning from mild symptoms (e.g., olfactory and gustatory deficits, hallucinations, and headache) to severe complications (e.g., stroke, seizures, encephalitis, and neurally demyelinating lesions). The occurrence of single-pass subdural effusion, as described below, is extremely rare. CASE SUMMARY: A 56-year-old male patient presented with left-sided limb weakness and slurred speech as predominant clinical symptoms. Through comprehensive imaging and diagnostic assessments, he was diagnosed with cerebral infarction complicated by hemorrhagic transformation affecting the right frontal, temporal, and parietal regions. In addition, an intracranial infection with SARS-CoV-2 was identified during the rehabilitation process; consequently, an idiopathic subdural effusion developed. Remarkably, the subdural effusion underwent absorption within 6 d, with no recurrence observed during the 3-month follow-up. CONCLUSION: Subdural effusion is a potentially rare intracranial complication associated with SARS-CoV-2 infection.

Effectiveness and safety of a novel intravascular lithotripsy system for severe coronary calcification: CALCI-CRACK trial.

BACKGROUND: Intravascular lithotripsy is effective and safe for managing coronary calcification; however, available devices are limited, and complex lesions have been excluded in previous studies. This study aimed to investigate the effectiveness and safety of a novel intravascular lithotripsy system for severe calcification in a population with complex lesions. METHODS: CALCI-CRACK (ChiCTR2100052058) is a prospective, single-arm, multicenter study. The primary endpoint was the procedural success rate. Major safety endpoints included major adverse cardiovascular events (MACE) and target lesion failure (TLF) at 30 days and 6 months, and severe angiographic complications. Calcification morphology was assessed in the optical coherence tomography (OCT) subgroup. RESULTS: In total, 242 patients from 15 high-volume Chinese centers were enrolled, including 26.45% of patients with true bifurcation lesions, 3.31% with severely tortuous vessels, and 2.48% with chronic total occlusion, respectively. The procedural success rate was 95.04% (95% confidence interval 91.50-97.41%), exceeding the pre-specified performance goal of 83.4% (p<0.001). The 30-day and 6-month MACE rates were 4.13% and 4.55%, respectively. TLF rates at these time-points were 1.24% and 1.65%, respectively. Severe angiographic complications occurred in 0.42% of patients. In the OCT subgroup (n=93), 93.55% of calcified lesions were fractured, and minimal lumen area increased from 1.55 ± 0.55 mm2 to 4.91 ± 1.22 mm2 after stent implantation, with acute gain rate of 245 ± 102%. CONCLUSIONS: The novel intravascular lithotripsy system is effective and safe for managing severely calcified coronary lesions in a cohort that included true bifurcation lesions, severely tortuous vessels, and chronic total occlusion. (ChiCTR2100052058).

Enantioselective synthesis of spirooxindole-pyran derivatives via a remote inverse-electron-demand Diels-Alder reaction of ß,γ-unsaturated amides.

Novel construction methods for obtaining 3,4'-pyran spirooxindole heterocyclic skeletons have always been the focus of attention. Herein, we report a highly enantioselective inverse-electron-demand oxa-Diels-Alder cycloaddition reaction of a ß,γ-unsaturated pyrazole amide and a N-diphenyl isatin-derived oxodiene using a bifunctional catalyst. In addition, large-scale experiments confirmed the reliability of the reaction. The resultant products of this study can be further transformed.

A combined pre- and intra-operative nomogram in evaluation of degrees of liver cirrhosis predicts post-hepatectomy liver failure: a multicenter prospective study.

Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Trial Registration: Clinicaltrials.gov Identifier: NCT04076631.