Coxsackievirus A6 2C protein antagonizes IFN-ß production through MDA5 and RIG-I depletion.

IMPORTANCE: Coxsackievirus A6 (CV-A6) is a major emerging pathogen associated with atypical hand, foot, and mouth disease and can cause serious complications such as encephalitis, acute flaccid paralysis, and neurorespiratory syndrome. Therefore, revealing the associated pathogenic mechanisms could benefit the control of CV-A6 infections. In this study, we demonstrate that the nonstructural 2CCV-A6 suppresses IFN-ß production, which supports CV-A6 infection. This is achieved by depleting RNA sensors such as melanoma differentiation-associated gene 5 and retinoic acid-inducible gene I (RIG-I) through the lysosomal pathway. Such a function is shared by 2CEV-A71 and 2CCV-B3 but not 2CCV-A16, suggesting the latter might have an alternative way to promote viral replication. This study broadens our understanding of enterovirus 2C protein regulation of the RIG-I-like receptor signaling pathway and reveals a novel mechanism by which CV-A6 and other enteroviruses evade the host innate immune response. These findings on 2C may provide new therapeutic targets for the development of effective inhibitors against CV-A6 and other enterovirus infections.

An S-locus F-box protein as pollen S determinant targets non-self S-RNase underlying self-incompatibility in Citrus.

Self-incompatibility (SI) is a crucial mechanism that prevents self-fertilization and inbreeding in flowering plants. Citrus exhibits SI regulated by a polymorphic S-locus containing an S-RNase gene and multiple S-locus F-box (SLF) genes. It has been documented that S-RNase functions as the pistil S determinant, but there is no direct evidence that the SLF genes closely linked with S-RNase function as pollen S determinants in Citrus. This study assembled the genomes of two pummelo (Citrus grandis) plants, obtained three novel complete and well-annotated S-haplotypes, and isolated 36 SLF or SLF-like alleles on the S-loci. Phylogenetic analysis of 138 SLFs revealed that the SLF genes were classified into 12 types, including six types with divergent or missing alleles. Furthermore, transformation experiments verified that the conserved S6-SLF7a protein can lead to the transition of SI to self-compatibility by recognizing non-self S8-RNase in 'Mini-Citrus' plants (S7S8 and S8S29, Fortunella hindsii), a model plant for citrus gene function studies. In vitro assays demonstrated interactions between SLFs of different S haplotypes and the Skp1-Cullin1-F-box subunit CgSSK1 protein. This study provides direct evidence that SLF controls the pollen function in Citrus, demonstrating its role in the 'non-self recognition' SI system.

2ß-Acetoxyferruginol derivatives as α-glucosidase inhibitors: Synthesis and biological evaluation.

To find potential α-glucosidase inhibitors, a series of 2ß-acetoxyferuginol derivatives containing cinnamic acid (WXC-1 âˆ¼ 25) were synthesized and investigated their biological activity. All derivatives (WXC-1 âˆ¼ 25) displayed better inhibitory activity (IC50 values: 7.56 ± 1.35 âˆ¼ 25.63 ± 1.72 µM) compared to acarbose (IC50 vaule: 564.28 ± 48.68 µM). In particularly, WXC-25 with 4-hydroxycinnamic acid section showed the best inhibitory activity (IC50 vaule: 2.02 ± 0.14 µM), ∼75-fold stronger than acarbose. Kinetics results suggested WXC-25 being one reversible non-competition inhibitors. Fluorescence quenching results indicated that WXC-25 quenched the fluorescence of α-glucosidase in a static manner. 3D fluorescence spectra results indicated that WXC-25 treatment could cause the conformation changes of α-glucosidase. Moreover, molecular docking simulated the detailed interaction of WXC25 with α-glucosidase.

Different biomarker ratios in peripheral blood have limited value in diagnosing periprosthetic joint infection after total joint arthroplasty: a single-center, retrospective study.

BACKGROUND: Periprosthetic joint infection (PJI) is a severe complication that can occur after total joint arthroplasty (TJA). The timely and accurate diagnosis of PJI is the key to treatment. This study investigated the diagnostic value of platelet to lymphocyte ratio (PLR), platelet count to mean platelet volume ratio (PVR), neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) in PJI after total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: We performed a retrospective analysis of the patients who underwent revision hip or knee arthroplasty at our Institute between June 2015 and June 2020. Of the 187 patients reviewed, 168 were included in the study. According to the diagnostic criteria of the Musculoskeletal Infection Society (MSIS), 58 patients were in the PJI group, and 110 patients were in the aseptic loosening (AL) group. We recorded and compared the preoperative peripheral blood white blood cell (WBC) count, platelet count (PLT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), PLR, PVR, NLR, and MLR in both groups. The diagnostic performance of the WBC, PLT, PLR, PVR, NLR, and MLR individually and in combination with the ESR and CRP for PJI diagnosis was evaluated by receiver operating characteristic (ROC) curves, and the sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: Compared to those in the AL group, the mean WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR in the peripheral blood of the PJI group were significantly greater (P < 0.05). The analysis of the ROC curve revealed that the ESR, CRP, PLR, PVR, NLR, and MLR in peripheral blood had moderate effectiveness in diagnosing PJI, with area under the curve (AUC) values of 0.760 (95% CI: 0.688-0.823), 0.758 (95% CI: 0.687-0.821), 0.714 (95% CI: 0.639-0.781), 0.709 (95% CI: 0.634-0.777), 0.723 (95% CI: 0.649-0.789), and 0.728 (95% CI: 0.654-0.793), respectively. Conversely, the WBC and PLT counts demonstrated poor diagnostic value for PJI, with AUC values of 0.578 (95% CI: 0.499-0.653) and 0.694 (95% CI: 0.619-0.763), respectively. The results of the prediction model calculations revealed that the combined AUC of the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR was the highest at 0.853 (95% CI, 0.790-0.909), indicating good value in the diagnosis of PJI, with a sensitivity of 82.8% and a specificity of 72.7%. Moreover, the novel composite of parameters improved the accuracy and reliability in diagnosing PJI compared to the traditional biomarkers ESR and CRP (P = 0.015). CONCLUSION: Our study suggested that the diagnostic value of the peripheral blood biomarkers PLR, PVR, NLR, and MLR for diagnosing PJI is limited and not superior to that of the ESR or CRP. However, when the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR are combined, the diagnostic performance of PJI in TJA patients can be improved.

Incidence of cardiovascular mortality among head and neck cancer patients.

BACKGROUND: While treatment advancements have prolonged the lives of patients with head and neck cancer, the subgroups of these patients at higher risk for cardiovascular disease (CVD) mortality remain unclear. METHODS: We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with head and neck cancer from 2000 to 2019. We compared their CVD mortality against the general US population using standardized mortality ratios (SMRs). RESULTS: Our analysis included 474,366 patients, identifying that 14% of deaths were due to CVD, with an SMR of 1.19. Notably, patients under the age of 39 had a CVD SMR increase of over 100-fold. Those with distant tumor stages showed the highest CVD SMR of 1.52 (95% CI 1.50-1.54). An upward trend in SMR to 2.53 (95% CI 2.51-2.56) was observed from 2011 to 2019. Within the initial 5-year post-diagnosis, the SMR for CVD was 3.17 (95% CI 3.14-3.20), which exceeded the general population's rates but declined in the 5-20-year range after diagnosis. Patients who did not any therapy had the greatest CVD SMR of 2.26 (95% CI 2.24-2.28). Hypopharyngeal cancer patients exhibited the highest CVD SMR of 1.54 (95% CI 1.52-1.56). CONCLUSIONS: The study highlights that head and neck cancer patients, especially younger individuals and those with advanced disease stages, face substantial CVD mortality risks. The CVD SMR peaks within 5 years following diagnosis. Patients abstaining from treatment bear the highest risk of CVD mortality. Cardioprotective measures should be considered critical for this patient population.

Design of Stable Chiral Aminosulfonium Ylides and Their Catalytic Asymmetric Synthesis.

The isolation and catalytic enantioselective synthesis of configurationally stable S-stereogenic sulfonium ylides have been significant challenges in the field of asymmetric synthesis. These reactive intermediates are crucial for a variety of synthetic transformations, yet their inherent tendency towards rapid inversion at the sulfur stereocenter has hindered their practical utilization. Conventional approaches have focused on strategies that incorporate a C=S bond-containing cyclic framework to help mitigate this stereochemical lability. In this work, we present an alternative tactic that leverages the stabilizing influence of an adjacent N-atom and cyclic sulfide moiety. Exploiting a copper catalyzed enantioselective intermolecular carbene transfer reaction, structurally diverse S-stereogenic aminosulfonium ylides have been achieved in excellent yields and enantioselectivities. Experimental results indicate that the careful selection of 2-diazo-1,3-diketone precursors is crucial for achieving optimal stereoinduction in this transformation. The resulting highly enantioenriched aminosulfonium ylides allow for further stereospecific elaborations to furnish aminosulfonium ylide oxides and sulfinamide. This work expands the boundaries of chiral sulfonium ylide chemistry, providing access to a broad range of previously elusive S-stereogenic aminosulfonium ylide scaffolds.

Enantiocontrolled Total Synthesis of (-)-Retigeranic Acid A.

The asymmetric total synthesis of (-)-retigeranic acid A has been realized. The key features of the current synthesis include (1) a Pt-catalyzed Conia-ene 5-exo-dig cyclization of enolyne to establish the key quaternary stereochemical center of C-10 (D/E ring), (2) an intramolecular diastereoselective Prins cyclization to construct the trans-hydrindane backbone (A/B ring), and (3) a late-stage intramolecular Fe-mediated hydrogen atom transfer (HAT) Baldwin-disfavored 5-endo-trig radical cyclization to rapidly assemble vicinal quaternary centers and the core structure of (-)-retigeranic acid A (C ring).

Analysis of Cytological Misdiagnosis and Oversight of Adenoid Cystic Carcinoma of Salivary Gland.

OBJECTIVE: In this article on adenoid cystic carcinoma (ACC) of salivary gland, we intend to summarize the causes of misdiagnosis and oversight of ACC hoping to improve cytological diagnostic accuracy, clinical management and patient treatment. METHODS: The study retrospectively reviewed 32 patients with ACC of salivary gland, registered at the Affiliated Hospital of Southwest Medical University from July 2014 to June 2021. These cases were diagnosed by FNA and surgical excision biopsy. All cytopathological results were retrospectively categorized according to Milan system for reporting salivary gland cytopathology (MSRSGC). The accuracy of FNA was verified by surgical excision biopsy. RESULTS: Of these 32 patients, 16 (50.0%) cases were male, and 16 (50.0%) were female. Their age ranged from 21 to 79 years, with an average age of 50.32 years. The highest incidence (15/32, 46.9%) of ACC was observed in patients between 41 and 50 years of age. 10 cases (31.3%) occurred in the parotid gland, 9 cases (28.1%) in the submandibular gland, 9 cases (28.1%) in the sublingual gland, 3 cases (9.4%) in the palate, and 1 case (3.1%) in the lip. Among the 32 cases of ACC, 23 cases (71.9%) were classified to VI, 4 cases (12.5%) to IVa, and 5 cases (15.6%) to II by MSRSGC. A comparison of the FNA results with biopsy showed that the accuracy of FNA in ACC of salivary gland is 71.9%. Being able to identify the cytomorphological features is the key factor for accurate diagnosis of ACC of the salivary gland. CONCLUSION: Our results confirm that FNA is an important initial screening in the diagnosis of ACC of salivary gland. Increased study of the cytomorphology of ACC is beneficial for more accurate diagnosis of ACC, to reduce misdiagnosis and oversight.

Giant cell tumor of tendon sheath: A report of 216 cases.

BACKGROUND: In this article on giant cell tumor of tendon sheath (GCTTS), we intend to summarize and analyze the clinical and pathological features of GCTTS hoping to improve clinical management and patient treatment. METHODS: The study retrospectively reviewed 216 patients of GCTTS, registered at the Affiliated Hospital of Southwest Medical University from January 2010 to December 2020. These cases were diagnosed by surgical excision. The clinicopathological features and the prognosis were reviewed in the light of the current literature. RESULTS: Of these 216 GCTTS patients, 72 were males (33.3%) and 144 females (66.7%), with a ratio male-to-female of 1:2. The patients' age ranged from 5 to 82, the average being 41.5 years at diagnosis. A total of 96 cases (44.4%) occurred in the hand region, followed by 35 cases (16.2%) in the knee, 32 cases (14.8%) in the foot, 25 cases (11.6%) in the ankle, 12 cases (5.6%) in the wrist, 12 cases (5.6%) in the leg, 2 cases (0.9%) in the head, 1 case (0.5%) in the forearm, and 1 case (0.5%) inside and outside the spinal channel. Histopathology mainly revealed large synovial-like monocytes, small monocytes, and osteoclast-like giant cells. CONCLUSION: Our results confirm that GCTTS predominantly occurs in the hands of young women. Complete surgical resection with long-term follow-up is the preferred management.

[Calcitonin gene-related peptides protect against oxidative stress-induced lung injury via increasing autophagy in neonatal rats].

Our previous studies have shown that calcitonin gene-related peptide (CGRP) exerts protective effects on the acute lung injury induced by oxidative stress. This study was aimed to investigate whether autophagy was involved in the protection of CGRP against oxidative stress-induced lung injury in neonatal rats. Newborn Sprague-Dawley (SD) rats were randomly divided into five groups: Control group, oxidative stress model group (Model group), Model + CGRP group, Model + CGRP + Rapamycin (an autophagy agonist) group, and Model + CGRP + LY294002 (an autophagy inhibitor) group. The model of hyperoxia-induced lung injury was established by continuous inhalation of oxygen (FiO2 = 90%-95%) for 14 days in neonatal SD rats. Pathological changes of lung tissue were observed by hematoxylin and eosin (HE) staining, and mean linear intercept (MLI) was measured. The quantitative changes of autophagic vesicles (AV) in type II alveolar epithelial cells (AECII) were measured under the transmission electron microscope. The protein expressions of Caspase-3, Bcl-2, mTOR, and Beclin-1 in lung tissue lysates were detected by Western blot. The results showed that, compared to the Model group at the same time point, the number of AV in AECII and the expression level of Beclin-1 protein of the lung tissue were increased, while the expression level of mTOR protein was decreased, with alleviated pathological changes, reduced MLI value and Caspase-3 protein expression level, increased Bcl-2 protein expression level in the lung tissue of Model + CGRP group. In addition, we found that the protective effect of CGRP on hyperoxia-induced lung injury could be enhanced by autophagy activator Rapamycin and abolished by autophagy inhibitor LY294002. Together, these findings indicate that CGRP could attenuate hyperoxia-induced lung injury in neonatal rats by enhancing autophagy.

Interleukin-33 alleviates diabetic cardiomyopathy through regulation of endoplasmic reticulum stress and autophagy via insulin-like growth factor-binding protein 3.

Prolonged endoplasmic reticulum (ER) stress is the key driving force behind diabetic cardiomyopathy (DCM). Autophagy is extensively implicated in adaptive mechanisms for cell survival. Interleukin-33 (IL-33) is known to be a potent cardiac protector, but its roles in DCM, ER stress, and autophagy are currently unknown. We aimed to explore the effects of IL-33 on DCM and characterize the roles that ER stress and autophagy play in DCM. The effects of IL-33 on DCM, ER stress, and autophagy were characterized both in db/db mice and in palmitic acid (PA)-treated cardiomyocytes. The manipulators of ER stress and autophagy were used to clarify their roles in DCM remittance conferred by IL-33. Gene expression analysis was used to identify IL-33-dependent regulators of ER stress and autophagy. Both db/db mice and PA-treated cells presented with enhanced levels of ER stress, apoptosis, and lipid deposition, as well as impaired autophagy, all of which could be reversed by IL-33. Treatment with IL-33 improved the cardiac diastolic function of diabetic mice. Nonselective autophagy inhibitors, such as 3-methyladenine (3-MA) or wortmannin, abolished the protective effects of IL-33, resulting in an increase in both ER stress and apoptosis. Strikingly, insulin-like growth factor-binding protein 3 (IGFBP3) was identified as the gene most significantly differentially expressed between IL-33 and control groups. Knockdown of IGFBP3 expression, similar to the effect of nonselective autophagy inhibitors, resulted in high levels of ER stress, impaired autophagy, and apoptosis that were not rescued upon treatment with IL-33. IL-33 abates DCM by alleviating ER stress and promoting autophagy. IGFBP3 is essential for IL-33-induced ER stress resolution and autophagic enhancement during DCM.

Knockdown of Long Noncoding RNAs of Maternally Expressed 3 Alleviates Hyperoxia-Induced Lung Injury via Inhibiting Thioredoxin-Interacting Protein-Mediated Pyroptosis by Binding to miR-18a.

Long-term hyperoxia exposure may cause lung damage with characteristic inflammation. Long noncoding RNA of maternally expressed 3 (MEG3) is up-regulated in lung tissues exposed to hyperoxia; however, the underlying mechanism is unclear. Hyperoxia-induced cells and mouse models were used to study these mechanisms. Molecular assays were used to detect cell viability, cytotoxicity, and expression of miR-18a, MEG3, and inflammatory cytokines. The interaction among MEG3, miR-18a, and thioredoxin-interacting protein (TXNIP) was verified; and pyroptosis-related proteins were analyzed. The in vivo model was established by exposing MEG3 knockdown mice to hyperoxia. Hematoxylin and eosin staining was used to assess pathologic alterations of lung tissues. Hyperoxia suppressed cell viability, induced cell damage, and exacerbated the secretion of IL-1ß and IL-18. Hyperoxia inhibited miR-18a, with increased expression of MEG3, TXNIP, and nonobese diabetic-like receptor family pyrin domain containing 3 (NLRP3). MEG3 aggravated TXNIP expression by binding to miR-18a. Knockdown of MEG3 rescued hyperoxia-induced pyroptosis by up-regulating miR-18a. Furthermore, knockdown of MEG3 inhibited NLRP3 inflammasome activity and caspase-1 signaling by miR-18a. In vivo knockdown of MEG3 and overexpression of miR-18a relieved hyperoxia-induced lung injury via restraining NLRP3 inflammasome-mediated pyroptosis, whereas miR-18a inhibition reversed these effects. In conclusion, knockdown of MEG3 inhibits pyroptosis to alleviate hyperoxia lung injury by suppressing NLRP3 inflammasome and caspase-1 signaling via regulating miR-18a-TXNIP axis.

In vitro and in silico studies of bis (indol-3-yl) methane derivatives as potential α-glucosidase and α-amylase inhibitors.

In this paper, bis (indol-3-yl) methanes (BIMs) were synthesised and evaluated for their inhibitory activity against α-glucosidase and α-amylase. All synthesised compounds showed potential α-glucosidase and α-amylase inhibitory activities. Compounds 5 g (IC50: 7.54 ± 1.10 µM), 5e (IC50: 9.00 ± 0.97 µM), and 5 h (IC50: 9.57 ± 0.62 µM) presented strongest inhibitory activities against α-glucosidase, that were ∼ 30 times stronger than acarbose. Compounds 5 g (IC50: 32.18 ± 1.66 µM), 5 h (IC50: 31.47 ± 1.42 µM), and 5 s (IC50: 30.91 ± 0.86 µM) showed strongest inhibitory activities towards α-amylase, ∼ 2.5 times stronger than acarbose. The mechanisms and docking simulation of the compounds were also studied. Compounds 5 g and 5 h exhibited bifunctional inhibitory activity against these two enzymes. Furthermore, compounds showed no toxicity against 3T3-L1 cells and HepG2 cells.HighlightsA series of bis (indol-3-yl) methanes (BIMs) were synthesised and evaluated inhibitory activities against α-glucosidase and α-amylase.Compound 5g exhibited promising activity (IC50 = 7.54 ± 1.10 µM) against α-glucosidase.Compound 5s exhibited promising activity (IC50 = 30.91 ± 0.86 µM) against α-amylase.In silico studies were performed to confirm the binding interactions of synthetic compounds with the enzyme active site.

Enantioselective Catalytic Aldehyde α-Alkylation/Semipinacol Rearrangement: Construction of α-Quaternary-δ-Carbonyl Cycloketones and Total Synthesis of (+)-Cerapicol.

An enantioselective aldehyde α-alkylation/semipinacol rearrangement was achieved through organo-SOMO catalysis. The catalytically generated enamine radical cation serves as a carbon radical electrophile that can stereoselectively add to the alkene of an allylic alcohol and initiate ensuing ring-expansion of cyclopropanol or cyclobutanol. This tandem reaction enables the production of a wide range of nonracemic functionalizable α-quaternary-δ-carbonyl cycloketones in high yields and excellent enantioselectivity from simple aldehydes and allylic alcohols. As a key step, the intramolecular reaction was also successfully applied in the asymmetric total synthesis of (+)-cerapicol.

[Risk factors for cow's milk protein allergy in infants: a multicenter survey].

OBJECTIVE: To investigate the risk factors for cow's milk protein allergy (CMPA) among infants through a multicenter clinical study. METHODS: A total of 1 829 infants, aged 1-12 months, who attended the outpatient service of the pediatric department in six hospitals in Shenzhen, China from June 2016 to May 2017 were enrolled as subjects. A questionnaire survey was performed to screen out suspected cases of CMPA. Food avoidance and oral food challenge tests were used to make a confirmed diagnosis of CMPA CMPA. A multivariate logistic regression analysis was used to investigate the risk factors for CMPA. RESULTS: Among the 1 829 infants, 82 (4.48%) were diagnosed with CMPA. The multivariate logistic regression analysis showed that maternal food allergy (OR=4.91, 95%CI: 2.24-10.76, P<0.05), antibiotic exposure during pregnancy (OR=3.18, 95%CI: 1.32-7.65, P<0.05), and the introduction of complementary food at an age of <4 months (OR=3.55, 95%CI: 1.52-8.27, P<0.05) were risk factors for CMPA, while exclusive breastfeeding (OR=0.21, 95%CI: 0.08-0.58, P<0.05) and the introduction of complementary food at an age of >6 months (OR=0.38, 95%CI: 0.17-0.86, P<0.05) were protective factors. CONCLUSIONS: The introduction of complementary food at an age of <4 months, maternal food allergy, and antibiotic exposure during pregnancy are risk factors for CMPA in infants.

Divergent Pathogenic Properties of Circulating Coxsackievirus A6 Associated with Emerging Hand, Foot, and Mouth Disease.

Coxsackievirus A6 (CV-A6) is an emerging pathogen associated with hand, foot, and mouth disease (HFMD). Its genetic characterization and pathogenic properties are largely unknown. Here, we report 39 circulating CV-A6 strains isolated in 2013 from HFMD patients in northeast China. Three major clusters of CV-A6 were identified and related to CV-A6, mostly from Shanghai, indicating that domestic CV-A6 strains were responsible for HFMD emerging in northeast China. Four full-length CV-A6 genomes representing each cluster were sequenced and analyzed further. Bootscanning tests indicated that all four CV-A6-Changchun strains were most likely recombinants between the CV-A6 prototype Gdula and prototype CV-A4 or CV-A4-related viruses, while the recombination pattern was related to, yet distinct from, the strains isolated from other regions of China. Furthermore, different CV-A6 strains showed different capabilities of viral replication, release, and pathogenesis in a mouse model. Further analyses indicated that viral protein 2C contributed to the diverse pathogenic abilities of CV-A6 by causing autophagy and inducing cell death. To our knowledge, this study is the first to report lethal and nonlethal strains of CV-A6 associated with HFMD. The 2C protein region may play a key role in the pathogenicity of CV-A6 strains.IMPORTANCE Hand, foot, and mouth disease (HFMD) is a major and persistent threat to infants and children. Besides the most common pathogens, such as enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16), other enteroviruses are increasingly contributing to HFMD. The present study focused on the recently emerged CV-A6 strain. We found that CV-A6 strains isolated in Changchun City in northeast China were associated with domestic origins. These Changchun viruses were novel recombinants of the CV-A6 prototype Gdula and CV-A4. Our results imply that measures to control CV-A6 transmission are urgently needed. Further analyses revealed differing pathogenicities in strains isolated in a neonatal mouse model. One of the possible causes has been narrowed down to the viral protein 2C, using phylogenetic studies, viral sequences, and direct tests on cultured human cells. Thus, the viral 2C protein is a promising target for antiviral drugs to prevent CV-A6-induced tissue damage.

Catalytic Asymmetric Total Syntheses of (-)-Galanthamine and (-)-Lycoramine.

The catalytic asymmetric total syntheses of the biologically important and therapeutically valuable Amaryllidaceae alkaloids (-)-galanthamine and (-)-lycoramine have been divergently achieved from commercially available 3-butyn-1-ol. A newly developed spirocyclic pyrrolidine (SPD)-catalyzed enantioselective Robinson annulation rapidly constructs the key cis-hydrodibenzofuran core, which bears an all-carbon quaternary stereocenter of the target molecules with an excellent stereoselective control. Additionally, the current asymmetric synthetic strategy provides an alternative approach toward the syntheses of (-)-galanthamine and its analogues.

The synthesis of cyanoformamides via a CsF-promoted decyanation/oxidation cascade of 2-dialkylamino-malononitriles.

A mild and efficient method for the synthesis of cyanoformamides from N,N-disubstituted aminomalononitriles with CsF as the promoter has been developed. This method features a wide substrate scope and high reaction efficiency, and will facilitate corresponding cyanoformamide-based biological studies and synthetic methodology development.

[Hematoma Expansion within 24 hours of Hypertensive Intracerebral Hemorrhage and Its Association with Signs on Nonenhanced Computed Tomography].

To explore the correlation between hematoma expansion within 24 hours of hypertensive intracerebral hemorrhage and signs on nonenhanced computed tomography(NECT). Methods The clinical data and CT images of 185 patients with hypertensive intracerebral hemorrhage were retrospectively analyzed.The differences in CT parameters were compared between the expansion group and the unexpanded group.Binary logistic regression analysis was performed on the indicators with statistical significance between the two groups to identify the potential correlation between CT parameters and hematoma expansion.The roles of blend sign,lobulation sign,and black hole sign in predicting early hematoma expansion were assessed. Results The CT quantitative data including initial volume,maximum diameter,minimum diameter,maximum CT value,mean CT value,difference between maximum diameter and minimum diameter showed no significant difference between these two group(all P>0.05).CT qualitative data including blend sign,lobulation sign,and black hole sign were significantly different(P<0.05)but the differences became not significant after the hematoma broke into the ventricles.Binary logistic regression analysis showed that blend sign,lobulation sign,and black hole sign were independent risk factors for early hematoma expansion,with sensitivity,specificity,positive predictive value,and negative predictive value of the combined signs and the early hematoma expansion calculated by the four-fold table method being 78.4%,59.0%,42.1%,and 87.8%,respectively,and the Youden index was 0.374.Its Youden index was closer to 1 than the blend sign,the black hole sign,and the lobulation sign. Conclusion The blend sign,lobulation sign,and black hole sign in NECT can be used to predict hematoma expansion within 24 hours after hypertensive cerebral hemorrhage.

Organo-Cation Catalyzed Asymmetric Homo/Heterodialkylation of Bisoxindoles: Construction of Vicinal All-Carbon Quaternary Stereocenters and Total Synthesis of (-)-Chimonanthidine.

A novel chiral spirocyclic amide (SPA)-derived triazolium organocatalyst has been designed and demonstrated to effect asymmetric homo- and heterodialkylations of various bisoxindoles, enabling enantioselective construction of vicinal all-carbon quaternary stereocenters. These reactions feature excellent enantio- and diastereoselectivities (up to 99% ee and >20:1 dr) as well as good to high yields (up to 89% over two steps). As an application of this methodology, the first asymmetric total synthesis of (-)-chimonanthidine has been achieved.