Inhibiting SHP2 reduces glycolysis, promotes microglial M1 polarization, and alleviates secondary inflammation following spinal cord injury in a mouse model.

JOURNAL/nrgr/04.03/01300535-202503000-00030/figure1/v/2024-06-17T092413Z/r/image-tiff Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2 (SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.

WaterBiSeg-Net: An underwater bilateral segmentation network for marine debris segmentation.

The cleanup of marine debris is an urgent problem in marine environmental protection. AUVs with visual recognition technology have gradually become a central research issue. However, existing recognition algorithms have slow inference speeds and high computational overhead. They are also affected by blurred images and interference information. To solve these problems, a real-time semantic segmentation network is proposed, called WaterBiSeg-Net. First, we propose the Multi-scale Information Enhancement Module to solve the impact of low-definition and blurred images. Then, to suppress the interference of background information, the Gated Aggregation Layer is proposed. In addition, we propose a method that can extract boundary information directly. Finally, extensive experiments on SUIM and TrashCan datasets show that WaterBiSeg-Net can better complete the task of marine debris segmentation and provide accurate segmentation results for AUVs in real-time. This research offers a low computational cost and real-time solution for AUVs to identify marine debris.

Colchicine poisoning: Case report of three homicides in a family.

Background: Colchicine is a common therapeutic agent for inflammatory conditions such as gout, yet its narrow therapeutic range frequently results in cases of overdose and subsequent poisoning. Acute colchicine poisoning can be difficult to identify due to its nonspecific clinical manifestations, posing a diagnostic challenge for emergency physicians without a clear history of colchicine ingestion. Case presentation: This report describes a tragic case of acute colchicine poisoning that resulted in three familial homicides. The patients presented with fever, abdominal pain, and diarrhea, which rapidly escalated to shock during their emergency department visits. Laboratory tests revealed a marked leukocytosis, mild elevation in procalcitonin (PCT), significantly elevated creatine kinase (CK) and CK-MB levels, and liver function abnormalities. Despite treatment with carbapenem antibiotics and aggressive fluid resuscitation, the patients' condition deteriorated, marked by a progressive decline in leukocytes and neutrophils. Initially misdiagnosed as septic shock, the ineffectiveness of the standard treatment protocols led to a fatal outcome for all three individuals. Conclusion: Emergency physicians should consider acute colchicine poisoning as a differential diagnosis in patients presenting with shock and the following clinical indicators: (1) pronounced increase in peripheral leukocytes with a disproportionate rise in neutrophils; (2) discordance between the level of serum procalcitonin and the severity of presumed septic shock; (3) early increase in serum creatine kinase (CK) and CK-MB; (4) poor response to antibiotics and resuscitative efforts, accompanied by a continuous decrease in white blood cells and neutrophils. This case underscores the critical need for awareness of colchicine toxicity in the emergency setting, particularly when the clinical presentation mimics septic shock but fails to respond to standard treatments.

Progress of Research into Preformed Particle Gels for Profile Control and Water Shutoff Techniques.

Gel treatment is an economical and efficient method of controlling excessive water production. The gelation of in situ gels is prone to being affected by the dilution of formation water, chromatographic during the transportation process, and thus controlling the gelation time and penetration depth is a challenging task. Therefore, a novel gel system termed preformed particle gels (PPGs) has been developed to overcome the drawbacks of in situ gels. PPGs are superabsorbent polymer gels which can swell but not dissolve in brines. Typically, PPGs are a granular gels formed based on the crosslinking of polyacrylamide, characterized by controllable particle size and strength. This work summarizes the application scenarios of PPGs and elucidates their plugging mechanisms. Additionally, several newly developed PPG systems such as high-temperature-resistant PPGs, re-crosslinkable PPGs, and delayed-swelling PPGs are also covered. This research indicates that PPGs can selectively block the formation of fractures or high-permeability channels. The performance of the novel modified PPGs was superior to in situ gels in harsh environments. Lastly, we outlined recommended improvements for the novel PPGs and suggested future research directions.

Unraveling the role of carboxylate groups and elastin particle size in medial calcification.

While it is known that calcium phosphate (CaP) minerals deposit in elastin-rich medial layers of arteries during medial calcification, their nucleation and growth sites are still debated. Neutral carbonyl groups and carboxylate groups are possible candidates. Also, while it is known that elastin degradation leads to calcification, it is unclear whether this is due to formation of new carboxylate groups or elastin fragmentation. In this work, we disentangle effects of carboxylate groups and particle size on elastin calcification; in doing so, we shed light on CaP mineralization sites on elastin. We find carboxylate groups accelerate calcification only in early stages; they mainly function as Ca2+ ion chelation sites but not calcification sites. Their presence promotes formation (likely on Ca2+ ions adsorbed on nearby carbonyl groups) of CaP minerals with high calcium-to-phosphate ratio as intermediate phases. Larger elastin particles calcify slower but reach similar amounts of CaP minerals in late stages; they promote direct formation of hydroxyapatite and CaP minerals with low calcium-to-phosphate ratio as intermediate phases. This work provides new perspectives on how carboxylate groups and elastin particle size influence calcification; these parameters can be tuned to study the mechanism of medial calcification and design drugs to inhibit the process.

Comparative transcriptome analysis of canola carrying a single vs stacked resistance genes against clubroot.

Pyramiding resistance genes may expand the efficacy and scope of a canola variety against clubroot (Plasmodiophora brassicae), a serious threat to canola production in western Canada. However, the mechanism(s) of multigenic resistance, especially the potential interaction among clubroot resistance (CR) genes, are not well understood. In this study, transcriptome was compared over three canola (Brassica napus L.) inbred/hybrid lines carrying a single CR gene in chromosome A03 (CRaM, Line 16) or A08 (Crr1rutb, Line 20), and both genes (CRaM+Crr1rutb, Line 15) inoculated with a field population (L-G2) of P. brassicae pathotype X, a new variant found in western Canada recently. The line16 was susceptible, while lines 15 and 20 were partially resistant. Functional annotation identified differential expression of genes (DEGs) involved in biosynthetic processes responsive to stress and regulation of cellular process; The Venn diagram showed that the partially resistant lines 15 and 20 shared 1,896 differentially expressed genes relative to the susceptible line 16, and many of these DEGs are involved in defense responses, activation of innate immunity, hormone biosynthesis and programmed cell death. The transcription of genes involved in Pathogen-Associated Molecular Pattern (PAMP)-Triggered and Effector-Triggered Immunity (PTI and ETI) was particularly up-regulated, and the transcription level was higher in line 15 (CRaM + Crr1rutb) than in line 20 (Crr1rutb only) for most of the DEGs. These results indicated that the partial resistance to the pathotype X was likely conferred by the CR gene Crr1rutb for both lines 15 and 20 that functioned via the activation of both PTI and ETI signaling pathways. Additionally, these two CR genes might have synergistic effects against the pathotype X, based on the higher transcription levels of defense-related DEGs expressed by inoculated line 15, highlighting the benefit of gene stacking for improved canola resistance as opposed to a single CR gene alone.

20-Week intramuscular toxicity study of rotigotine behenate extended-release microspheres for injection via intramuscular injection in cynomolgus monkeys.

Continuous dopaminergic stimulation (CDS) has become an important strategy for the development of drugs to treat Parkinson's disease (PD). Rotigotine behenate extended-release microspheres (RBEM) for injection represents a new treatment regime for CDS and is being applied for clinical trial. Our study in cynomolgus monkeys was a 20-week repeat dose toxicity investigation with RBEM at dosages of 90, 180, 360, with a 12-week recovery period. The results observed some irritations in the application site and surrounding tissues in Placebo microspheres and each dose of RBEM, was accompanied with increased white blood count and fibrinogen. RBEM-treated monkeys were additionally noted with a pharmacological action-related decrease in prolactin. These findings showed certain reversibility after the 12-week recovery phase. No clear sex difference was noted in the plasma exposure to rotigotine. The exposure generally increased in a dose-proportional manner. In summary, major toxicological effects are associated with the dopamine agonist-related properties of rotigotine, and the removal of foreign bodies caused by p oly (lactide-co-glycolide) (PLGA)and sodium carboxymethyl cellulose (SCMC), and the no-observed-adverse-effect-level (NOAEL) was 360 mg/kg.

Total Syntheses and Antibacterial Studies of Natural Isoflavones: Scandenone, Osajin, and 6,8-Diprenylgenistein.

Isoflavones are a class of natural products that exhibit a wide range of interesting biological properties, including antioxidant, hepatoprotective, antimicrobial, and anti-inflammatory activities. Scandenone (1), osajin (2), and 6,8-diprenylgenistein (3) are natural prenylated isoflavones that share the same polyphenol framework. In this research, the key intermediate 15 was used for the synthesis of the natural isoflavones 1-3, establishing a stereoselective synthetic method for both linear and angular pyran isoflavones. The antibacterial activities of 1-3 were also evaluated, and all of them displayed good antibacterial activity against Gram-positive bacteria. Among them, 2 was the most potent one against MRSA, with a MIC value of 2 µg/mL, and the SEM assay indicated that the bacterial cell membranes of both MRSA and E. faecalis could be disrupted by 2. These findings suggest that this type of isoflavone could serve as a lead for the development of novel antibacterial agents for the treatment of Gram-positive bacterial infections.

H-151 attenuates lipopolysaccharide-induced acute kidney injury by inhibiting the STING-TBK1 pathway.

Sepsis is a severe systemic infectious disease that often leads to multi-organ dysfunction. One of the common and serious complications of sepsis is renal injury. In this study, we aimed to investigate the potential mechanistic role of a novel compound called H-151 in septic kidney injury. We also examined its impact on renal function and mouse survival rates. Initially, we confirmed abnormal activation of the STING-TBK1 signaling pathway in the kidneys of septic mice. Subsequently, we treated the mice with H-151 and observed significant improvement in sepsis-induced renal dysfunction. This was evidenced by reductions in blood creatinine and urea nitrogen levels, as well as a marked decrease in inflammatory cytokine levels. Furthermore, H-151 substantially improved the seven-day survival rate of septic mice, indicating its therapeutic potential. Importantly, H-151 also exhibited an inhibitory effect on renal apoptosis levels, further highlighting its mechanism of protecting against septic kidney injury. These study findings not only offer new insights into the treatment of septic renal injury but also provide crucial clues for further investigations into the regulatory mechanisms of the STING-TBK1 signaling pathway and potential drug targets.

Resilience of Canola to Plasmodiophora brassicae (Clubroot) Pathotype 3H under Different Resistance Genes and Initial Inoculum Levels.

In this study, we explored the resilience of a clubroot resistance (CR) stacking model against a field population of Plasmodiophora brassicae pathotype 3H. This contrasts with our earlier work, where stacking CRaM and Crr1rutb proved only moderately resistant to pathotype X. Canola varieties carrying Rcr1/Crr1rutb and Rcr1 + Crr1rutb were repeatedly exposed to 3H at low (1 × 104/g soil) and high (1 × 107/g soil) initial resting spore concentrations over five planting cycles under controlled environments to mimic intensive canola production. Initially, all resistant varieties showed strong resistance. However, there was a gradual decline in resistance over time for varieties carrying only a single CR gene, particularly with Crr1rutb alone and at the high inoculum level, where the disease severity index (DSI) increased from 9% to 39% over five planting cycles. This suggests the presence of virulent pathotypes at initially low levels in the 3H inoculum. In contrast, the variety with stacked CR genes remained resilient, with DSI staying below 3% throughout, even at the high inoculum level. Furthermore, the use of resistant varieties, carrying either a single or stacked CR genes, reduced the total resting spore numbers in soil over time, while the inoculum level either increased or remained high in soils where susceptible Westar was continuously grown. Our study demonstrates greater resistance resilience for stacking Rcr1 and Crr1rutb against the field population of 3H. Additionally, the results suggest that resistance may persist even longer in fields with lower levels of inoculum, highlighting the value of extended crop rotation (reducing inoculum) alongside strategic CR-gene deployment to maximize resistance resilience.

Dietary High Levels of Coconut Oil Replacing Fish Oil Did Not Affect Growth, but Promoted Liver Lipid Deposition of Orange-Spotted Groupers (Epinephelus coioides).

In this study, we conducted an 8-week feeding trial to investigate the effects of replacing fish oil (FO) with coconut oil (CO) on the growth performance, blood components, tissue fatty acid (FA) profile, and mRNA levels of genes related to lipid metabolism in the liver of the orange-spotted grouper (Epinephelus coioides). Five isolipidic and isoproteic diets were formulated through increasing the CO levels (0, 25%, 50%, 75%, and 100%, respectively). Triplicate groups of twenty-five fish (initial wet weight of about 22.4 g/fish) were fed one of the diets twice daily to apparent satiety. The 25% CO diet had the highest growth rate and feed utilization, and the 100% CO diet exhibited a comparable growth and feed utilization with that of the control diet, indicating a suitable FO substitute. Moreover, the hepatosomatic index, intraperitoneal fat rate, liver lipid content, as well as the serum HDL-C content and ALT activity had positive linear and/or quadratic responses, but the serum TC and LDL-C contents exhibited the opposite trend, with an increasing CO inclusion level. The FA profile in the liver and muscle generally mirrored the FA profile in the feed. Furthermore, the mRNA levels of the fas, acc, g6pd, srebp-1c, and δ6fad genes in the liver had positive linear and/or quadratic responses, but the mRNA levels of elovl 4 and elovl 5 had the opposite trend, with increasing dietary CO inclusion levels. When compared with the control diet, 25% and 50% CO diets up-regulated the mRNA levels of cpt 1, while the 75% and 100% CO diets down-regulated its mRNA levels. The hsl and atgl were down-regulated through the addition of dietary CO. The mRNA level of lpl was not affected by dietary treatments. Results showed that CO could completely replace FO without affecting growth performance, but high CO will lead to the significant liver lipid deposition and lower LC-PUFAs contents of fish flesh.

Lysine-mediated surface modification of cellulose nanocrystal films for multi-channel anti-counterfeiting.

Utilizing advanced multiple channels for information encryption offers a powerful strategy to achieve high-capacity and highly secure data protection. Cellulose nanocrystals (CNCs) offer a sustainable resource for developing information protection materials. In this study, we present an approach that is easy to implement and adapt for the covalent attachment of various fluorescence molecules onto the surface of CNCs using the Mannich reaction in aqueous-based medium. Through the use of the Mannich reaction-based surface modification technique, we successfully achieved multi-color fluorescence in the resulting CNCs. The resulting CNC derivatives were thoroughly characterized by two dimensional heteronuclear single quantum coherence nuclear magnetic resonance (2D HSQC NMR) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy and X-ray photoelectron (XPS) spectroscopy. Notably, the optical properties of CNCs were well maintained after modification, resulting in films exhibiting blue and red structural colors. This enables the engineering of highly programmable and securely encoded anti-counterfeit labels. Moreover, subsequent coating of the modified CNCs with MXene yielded a highly secure encrypted matrix, offering advanced security and encryption capabilities under ultraviolet, visible, and near-infrared wavelengths. This CNC surface-modification enables the development of multimodal security labels with potential applications across various practical scenarios.

Erratum: Exosomal miR-125b-5p deriving from mesenchymal stem cells promotes tubular repair by suppression of p53 in ischemic acute kidney injury: Erratum.

[This corrects the article DOI: 10.7150/thno.54550.].

Myo-inositol rescued insulin resistance and dyslipidemia in db/db mice.

Myo-inositol (MI), present in a variety of foods, is essential in several important processes of cell physiology. In this study, we explored the protective effects of MI against hyperglycemia and dyslipidemia in db/db mice, a typical animal model of type 2 diabetes mellitus (T2DM). MI supplement effectively suppressed the high plasma glucose and insulin levels and markedly relieved the insulin resistance (IR) in the db/db mice, comparable to metformin's effects. In MIN6 pancreatic ß cells, MI also restrained the upsurge of insulin secretion stimulated by high-concentration glucose but had no impact on the promoted cell proliferation. Moreover, MI abated the enhanced plasma triglyceride and total cholesterol levels in the db/db mice. Notably, the lipid droplet formation of mesenchymal stem cells (MSCs) from db/db mice was significantly diminished after the treatment of MI, indicating that MI could effectively inhibit the differentiation of db/db mouse MSCs into adipocytes. However, MI regretfully failed to control obesity in db/db mice. This work proved that MI significantly helped db/db mice's metabolic disorders, indicating that MI has potential as an effective adjunctive treatment for hyperglycemia and dyslipidemia in T2DM patients.

Preoperative and postoperative MRI-based models versus clinical staging systems for predicting early recurrence in hepatocellular carcinoma.

BACKGROUND: To predict the early recurrence of HCC patients who received radical resection using preoperative variables based on Gd-EOB-DTPA enhanced MRI, followed by the comparison with the postoperative model and clinical staging systems. METHODS: One hundred and twenty-nine HCC patients who received radical resection were categorized into the early recurrence group (n = 48) and the early recurrence-free group (n = 81). Through COX regression analysis, statistically significant variables of laboratory, pathologic, and Gd-EOB-DTPA enhanced MRI results were identified. The preoperative and postoperative models were established to predict early recurrence, and the prognostic performances and differences were compared between the two models and clinical staging systems. RESULTS: Six variables were incorporated into the preoperative model, including alpha-fetoprotein (AFP) level, aspartate aminotransferase/platelet ratio index (APRI), rim arterial phase hyperenhancement (rim APHE), peritumoral hypointensity on hepatobiliary phase (HBP), CERHBP (tumor-to-liver SI ratio on hepatobiliary phase imaging), and ADC value. Moreover, the postoperative model was developed by adding microvascular invasion (MVI) and histological grade. The C-index of the preoperative model and postoperative model were 0.889 and 0.901 (p = 0.211) respectively. Using receiver operating characteristic curve analysis (ROC) and decision curve analysis (DCA), it was determined that the innovative models we developed had superior predictive capabilities for early recurrence in comparison to current clinical staging systems. HCC patients who received radical resection were stratified into low-, medium-, and high-risk groups on the basis of the preoperative and postoperative models. CONCLUSION: The preoperative and postoperative MRI-based models built in this study were more competent compared with clinical staging systems to predict the early recurrence in hepatocellular carcinoma.

Decoding the Qu-aroma of medium-temperature Daqu starter by volatilomics, aroma recombination, omission studies and sensory analysis.

Qu-aroma is of great significance for evaluation the quality of Daqu starter. This study aimed to decode the Qu-aroma of medium-temperature Daqu (MT-Daqu) via "top-down" and "bottom-up" approaches. Firstly, 52 aroma descriptors were defined to describe the MT-Daqu aroma by quantitative descriptive analysis. Secondly, 193 volatile organic compounds (VOCs) were identified from 42 MT-Daqu samples by HS-SPME-GC-MS, and 43 dominant VOCs were screened out by frequence of occurrence or abundance. By Thin Film (TF)-SPME-GC-O-MS, 27 odors and 90 VOCs were detected in MT-Daqu mixture, and 14 odor-active VOCs were screened out by odor intensity. Thirdly, a five-level MT-Daqu aroma wheel was constructed by matching 52 aroma descriptors and 37 aroma-active VOCs. Finally, Qu-aroma of MT-Daqu was reconstructed with 37 aroma-active VOCs and evaluated by omission experiments. Hereinto, 26 key aroma-active VOCs were determined by OAV value ≥1, including isovaleric acid, 1-hexanol, isovaleraldehyde, 2-octanone, trimethylpyrazine, γ-nonalactone, 4-vinylguaiacol, etc.

Identification of stable reference genes for relative quantification of long RNA expression in urinary extracellular vesicles.

Urinary extracellular vesicles (uEVs) are rich in valuable biomolecule information which are increasingly recognized as potential biomarkers for various diseases. uEV long RNAs are among the critical cargos capable of providing unique transcriptome information of the source cells. However, consensus regarding ideal reference genes for relative long RNAs quantification in uEVs is not available as of date. Here we explored stable reference genes through profiling the long RNA expression by RNA-seq following unsupervised analysis and validation studies. Candidate reference genes were identified using four algorithms: NormFinder, GeNorm, BestKeeper and the Delta Ct method, followed by validation. RNA profile showed uEVs contained abundant long RNAs information and the core transcriptome was related to cellular structures, especially ribosome which functions mainly as translation, protein and RNA binding molecules. Analysis of RNA-seq data identified RPL18A, RPL11, RPL27, RACK1, RPSA, RPL41, H1-2, RPL4, GAPDH, RPS27A as candidate reference genes. RT-qPCR validation revealed that RPL41, RPSA and RPL18A were reliable reference genes for long RNA quantification in uEVs from patients with diabetes mellitus (DM), diabetic nephropathy (DN), IgA nephropathy (IgAN) and prostate cancer (PCA). Interestingly, RPL41 also outperformed traditional reference genes in renal tissues of DN and IgAN, as well as in plasma EVs of several types of cancers. The stable reference genes identified in this study may facilitate development of uEVs as novel biomarkers and increase the accuracy and comparability of biomarker studies.

The global distribution of the macrolide esterase EstX from the alpha/beta hydrolase superfamily.

Macrolide antibiotics, pivotal in clinical therapeutics, are confronting resistance challenges mediated by enzymes like macrolide esterases, which are classified into Ere-type and the less studied Est-type. In this study, we provide the biochemical confirmation of EstX, an Est-type macrolide esterase that initially identified as unknown protein in the 1980s. EstX is capable of hydrolyzing four 16-membered ring macrolides, encompassing both veterinary (tylosin, tidipirosin, and tilmicosin) and human-use (leucomycin A5) antibiotics. It uses typical catalytic triad (Asp233-His261-Ser102) from alpha/beta hydrolase superfamily for ester bond hydrolysis. Further genomic context analysis suggests that the dissemination of estX is likely facilitated by mobile genetic elements such as integrons and transposons. The global distribution study indicates that bacteria harboring the estX gene, predominantly pathogenic species like Escherichia coli, Salmonella enterica, and Klebsiella pneumoniae, are prevalent in 74 countries across 6 continents. Additionally, the emergence timeline of the estX gene suggests its proliferation may be linked to the overuse of macrolide antibiotics. The widespread prevalence and dissemination of Est-type macrolide esterase highlight an urgent need for enhanced monitoring and in-depth research, underlining its significance as an escalating public health issue.

Clinical Application of Artificial Intelligence in the Ultrasound Classification of Hepatic Cystic Echinococcosis.

Hepatic cystic echinococcosis (HCE) is a zoonotic disease that occurs when the larvae of Echinococcus granulosus parasitize the livers of humans and mammals. HCE has five subtypes, and accurate subtype classification is critical for choosing a treatment strategy. To evaluate the clinical utility of artificial intelligence (AI) based on convolutional neural networks (CNNs) in the classification of HCE subtypes via ultrasound imaging, we collected ultrasound images from 4,012 HCE patients at the First Affiliated Hospital of Xinjiang Medical University between 2008 and 2020. Specifically, 1,820 HCE images from 967 patients were used as the training and validation sets for the construction of the AI model, and the remaining 6,808 images from 3,045 patients were used as the test set to evaluate the performance of the AI models. The 6,808 images were randomly divided into six groups, and each group contained equal proportions of the five subtypes. The data of each group were analyzed by a resident physician. The accuracy of HCE subtype classification by the AI model and by manual inspection was compared. The AI HCE classification model showed good performance in the diagnosis of subtypes CE1, CE2, CE4, and CE5. The overall accuracy of the AI classification (90.4%) was significantly greater than that of manual classification by physicians (86.1%; P <0.05). The CNN can better identify the five subtypes of HCE on ultrasound images and should help doctors with little experience in more accurately diagnosing HCE.

[2+1] Cycloadditions Modulate the Hydrophobicity of Ni-N4 Single-Atom Catalysts for Efficient CO2 Electroreduction.

Microenvironment regulation of M-N4 single-atom catalysts (SACs) is a promising way to tune their catalytic properties toward the electrochemical CO2 reduction reaction. However, strategies that can effectively introduce functional groups around the M-N4 sites through strong covalent bonding and under mild reaction conditions are highly desired. Taking the hydrophilic Ni-N4 SAC as a representative, we report herein a [2+1] cycloaddition reaction between Ni-N4 and in situ generated difluorocarbene (F2C:), and enable the surface fluorocarbonation of Ni-N4, resulting in the formation of a super-hydrophobic Ni-N4-CF2 catalyst. Meanwhile, the mild reaction conditions allow Ni-N4-CF2 to inherit both the electronic and structural configuration of the Ni-N4 sites from Ni-N4. Enhanced electrochemical CO2-to-CO Faradaic efficiency above 98 % is achieved in a wide operating potential window from -0.7 V to -1.3 V over Ni-N4-CF2. In situ spectroelectrochemical studies reveal that a highly hydrophobic microenvironment formed by the -CF2- group repels asymmetric H-bonded water at the electrified interface, inhibiting the hydrogen evolution reaction and promoting CO production. This work highlights the advantages of [2+1] cycloaddition reactions on the covalent modification of N-doped carbon-supported catalysts.