Photoredox-catalyzed alkylarylation of activated alkenes via a ring-opening/Truce-Smiles rearrangement cascade.

A photoredox-catalyzed alkylarylation of activated alkenes via a radical C-C bond cleavage/Truce-Smiles rearrangement cascade is developed. The protocol features mild and redox-neutral conditions, broad substrate scope and excellent functional group compatibility, providing a facile and efficient approach to the long-chain distal keto-amides with all-carbon quaternary centers at the alpha position.

Genome-wide analysis of in vivo-evolved Candida auris reveals multidrug-resistance mechanisms.

Candida auris, an emerging and multidrug-resistant fungal pathogen, has led to numerous outbreaks in China. While the resistance mechanisms against azole and amphotericin B have been studied, the development of drug resistance in this pathogen remains poorly understood, particularly in in vivo-generated drug-resistant strains. This study employed pathogen whole-genome sequencing to investigate the epidemiology and drug-resistance mutations of C. auris using 16 strains isolated from two patients. Identification was conducted through Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and antimicrobial susceptibilities were assessed using broth microdilution and Sensititre YeastOne YO10. Whole-genome sequencing revealed that all isolates belonged to the South Asian lineage, displaying genetic heterogeneity. Despite low genetic variability among patient isolates, notable mutations were identified, including Y132F in ERG11 and A585S in TAC1b, likely linked to increased fluconazole resistance. Strains from patient B also carried F214L in TAC1b, resulting in a consistent voriconazole minimum inhibitory concentration of 4 µg/mL across all isolates. Furthermore, a novel frameshift mutation in the SNG1 gene was observed in amphotericin B-resistant isolates compared to susceptible ones. Our findings suggest the potential transmission of C. auris and emphasize the need to explore variations related to antifungal resistance. This involves analyzing genomic mutations and karyotypes, especially in vivo, to compare sensitive and resistant strains. Further monitoring and validation efforts are crucial for a comprehensive understanding of the mechanisms of drug resistance in C. auris.

Iron-Catalyzed Cyanide-Free Synthesis of Alkyl Nitriles: Oxidative Deconstruction of Cycloalkanones with Ammonium Salts and Aerobic Oxidation.

A sustainable, cyanide-free synthesis of alkyl nitriles via the aerobic oxidative deconstruction of unstrained cycloalkanones with ammonium salts has been developed. Using inexpensive and stable ammonium salts as the nitrogen source, a variety of alkyl nitriles containing a distal carbonyl group were obtained in good yields under visible-light-promoted iron catalysis. This protocol is characterized by mild conditions, abundant and environmentally benign materials, and high atom and step economy with minimal waste generation. The primary mechanism study revealed that 1O2 is likely to be involved in this reaction.

Association between irritable bowel syndrome and Parkinson's disease by Cohort study and Mendelian randomization analysis.

This study aimed to investigate the association between irritable bowel syndrome (IBS) and Parkinson's disease (PD) utilizing prospective cohort study and Mendelian randomization. The dataset contained a substantial cohort of 426,911 participants from the UK Biobank, discussing the association between IBS and PD with Cox proportional hazards models and case-control analysis while adjusting for covariates such as age, gender, ethnicity and education level. In univariate Cox regression model, the risk of PD was reduced in IBS patients (HR: 0.774, 95%CI: 0.625-0.956, P = 0.017), but the statistical significance diminished in the three models after adjusting for other variables. In a few subgroup analyses, IBS patients are less likely to develop into PD, and patients diagnosed with IBS after 2000 also had a lower risk (HR: 0.633, 95%CI: 0.403-0.994, P = 0.047) of subsequently developing PD. In addition, we matched five healthy control participants based on gender and age at the end of the study for each IBS patient diagnosed during the follow-up period, and logistic regression results (OR:1.239, 95%CI: 0.896-1.680, P = 0.181) showed that IBS was not associated with the risk of PD. Mendelian randomization did not find significant evidence of the causal relationship between IBS and Parkinson's disease (OR: 0.801, 95%CI: 0.570-1.278, P = 0.204). Overall, we suggest that IBS status is not associated with the risk of developing PD, and that these findings provide valuable insights into the clinical management and resource allocation of patients with IBS.

Two new furanone derivatives from the endophytic fungus Byssochlamys sp. and their cytotoxic activities.

Two new furanone derivatives, byssochlanones A-B (1-2) were purified from the endophytic fungus Byssochlamys sp. isolated from the wetland plant, Phragmites australis. Their structures were elucidated on the basis of extensive spectroscopic analyses. Compounds 1-2 represented typical furanone analogues which are not common in natural products. The absolute configuration of compounds 1-2 were identified through quantum-chemical electronic circular dichroism (ECD) calculation compared with their experimental CD. In addition, compounds 1-2 were tested for their cytotoxic activities against HCT-8 and Hela cancer cell lines, and compound 2 showed moderate activity against HCT-8 cells with IC50 value of 21.3 µM.

Effects of gibberellic acid, kinetin and indole butyric acid mixture on sorghum salinity tolerance and grain yield in saline-alkali coastal zone.

The development and utilization of coastal saline-alkali lands hold significant importance in mitigating the shortage of cultivated land resources in China, enhancing the agro-ecological environment in coastal saline and alkaline areas, and ensuring national food security. We set up both pot and field trials (randomized block design) at Xinxiang experimental station of Institute of Crop Science, Chinese Academy of Agricultural Sciences (ICS-CAAS) and Dongying Yellow River Delta Modern Agricultural Research Base in Shandong Province in 2021 and 2022, respectively. The experimental materials, Jiliang 1 and Jiliang 2, underwent seed dressing with GKI composites at concentrations of 2.5 and 5 mL·kg-1. These composites, which contained the main components of gibberellin, kinetin, and indole butyric acid, were denoted as GKI2.5 and GKI5.0, respectively. The control plots (CK) received water seed dressing. The aim was to assess the regulatory effects of GKI on salt tolerance and grain sorghum yield. Compared to CK, the GKI2.5 and GKI5.0 seed dressing treatments significantly enhanced the growth and development of the two grain sorghum varieties, increased antioxidant enzyme activity and soluble protein content of sorghum leaves, while reducing leaf malondialdehyde content. Moreover, the GKI treatments increased leaf net photosynthetic rate. Under field conditions, yields of Jiliang 1 and Jiliang 2 were enhanced by an average of 17.1% and 19.1%, respectively. In conclusion, GKI seed dressing treatment effectively promoted the growth and development of sorghum under salt stress. It enhanced the antioxidant and osmoregulatory capacities of leaves, reduced the level of membrane lipid peroxidation, and improved net photosynthetic rate of leaves, which together improved the salt tolerance and sorghum yield.

Causative Microorganisms Isolated from Patients with Intra-Abdominal Infections and Their Drug Resistance Profiles: An 11-Year (2011-2021) Single-Center Retrospective Study.

Objective: To investigate the distribution and antimicrobial susceptibility of causative microorganisms recovered from patients with intra-abdominal infections (IAIs). Methods: A total of 2,926 bacterial and fungal strains were identified in samples collected from 1,679 patients with IAIs at the Peking Union Medical College Hospital between 2011 and 2021. Pathogenic bacteria and fungi were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antimicrobial susceptibility testing (AST) was performed using the VITEK 2 compact system and the Kirby-Bauer method. AST results were interpreted based on the M100-Ed31 clinical breakpoints of the Clinical and Laboratory Standards Institute. Results: Of the 2,926 strains identified, 49.2%, 40.8%, and 9.5% were gram-negative bacteria, gram-positive bacteria, and fungi, respectively. Escherichia coli was the most prevalent pathogen in intensive care unit (ICU) and non-ICU patients; however, a significant decrease was observed in the isolation of E. coli between 2011 and 2021. Specifically, significant decreases were observed between 2011 and 2021 in the levels of extended-spectrum ß-lactamase (ESBL)-producing E. coli (from 76.9% to 14.3%) and Klebsiella pneumoniae (from 45.8% to 4.8%). Polymicrobial infections, particularly those involving co-infection with gram-positive and gram-negative bacteria, were commonly observed in IAI patients. Moreover, Candida albicans was more commonly isolated from hospital-associated IAI samples, while Staphylococcus epidermidis had a higher ratio in community-associated IAIs. Additionally, AST results revealed that most antimicrobial agents performed better in non-ESBL-producers than in ESBL-producers, while the overall resistance rates (56.9%-76.8%) of Acinetobacter baumanmii were higher against all antimicrobial agents than those of other common gram-negative bacteria. Indeed, Enterococcus faecium, Enterococcus faecalis, S. epidermidis, and S. aureus were consistently found to be susceptible to vancomycin, teicoplanin, and linezolid. Similarly, C. albicans exhibited high susceptibility to all the tested antifungal drugs. Conclusion: The distribution and antimicrobial susceptibility of the causative microorganisms from patients with IAIs were altered between 2011 and 2021. This finding is valuable for the implementation of evidence-based antimicrobial therapy and provides guidance for the control of hospital infections.

Iron-catalyzed alkoxyl radical-mediated C-C bond cleavage/phosphorothiolation: a new approach to functionalized S-alkyl phosphorothioates.

An efficient iron-catalyzed alkoxyl radical-mediated C-C bond cleavage/phosphorothiolation cascade is presented. This protocol features mild and redox neutral conditions, wide substrate scope and easy scalability, allowing straightforward access to functionalized S-alkyl organophosphorus compounds in moderate to good yields.

Divergent Construction of Azaheterocycles via Alkoxyl Radical-Triggered C-C Bond Cleavage/Cyclization of N-Functionalized Acrylamides.

An array of redox-neutral alkylation/cyclization cascade reactions of N-functionalized acrylamides with cycloalkyl hydroperoxides were achieved via the alkoxyl radical-triggered C-C bond cleavage. Through adjusting the radical acceptors on the N atom, a variety of keto-alkylated chain-containing azaheterocycles, including indolo[2,1-a]isoquinolin-6(5H)-ones, quinoline-2,4-diones, and pyrido[4,3,2-gh]phenanthridines were constructed by a one-pot procedure with good yields and excellent functional group tolerance.

Alkoxyl Radical-Mediated Ring Expansion/1,4-Difunctionalization of 1,3-Enynes upon Copper Catalysis.

A redox-neutral copper-catalyzed cascade reaction involving alkoxyl radical-mediated ring expansion/1,4-difunctionalization of 1,3-enynes was developed, offering a straightforward approach to the tetra-substituted allenes with macrolactone, CN, and CF3 functional groups. Remarkably, incorporation of the NH2 group onto the 1,3-enyne moiety enabled further cyclization to give a unique scaffold containing a lactone and an indole moiety.

Iron-Catalyzed Alkoxyl Radical-Induced C-C Bond Cleavage/gem-Difluoroalkylation Cascade.

An inexpensive iron-catalyzed alkoxyl radical-induced C-C bond cleavage/gem-difluoroalkylation cascade is presented. Regulated by the structure of alkoxyl radical precursors, fluorinated distal diketones were synthesized through a ring-opening strategy and difluoroalkylated medium-sized lactones and macrolactones were constructed via a ring-expansion strategy. Both protocols proceeded under mild and redox neutral conditions with a broad substrate scope and good functional group compatibility.

A cheap metal catalyzed ring expansion/cross-coupling cascade: a new route to functionalized medium-sized and macrolactones.

An efficient alkoxyl radical-triggered ring expansion/cross-coupling cascade was developed under cheap metal catalysis. Through the metal-catalyzed radical relay strategy, a wide range of medium-sized lactones (9-11 membered) and macrolactones (12, 13, 15, 18, and 19-membered) were constructed in moderate to good yields, along with diverse functional groups including CN, N3, SCN, and X groups installed concurrently. Density functional theory (DFT) calculations revealed that reductive elimination of the cycloalkyl-Cu(iii) species is a more favorable reaction pathway for the cross-coupling step. Based on the results of experiments and DFT, a Cu(i)/Cu(ii)/Cu(iii) catalytic cycle is proposed for this tandem reaction.

Phosphodiesterase 10A inhibitor PF-2545920 as a prospective agent for the clinical promotion of sperm motility.

Phosphodiesterase (PDE) inhibitors can improve sperm motility in patients with asthenozoospermia. However, the most commonly reported nonselective PDE inhibitor pentoxifylline and PDE5 inhibitor sildenafil have the disadvantages of requiring a high concentration and destroying sperm integrity. We examined the PDE10A inhibitor PF-2545920 to compare its ability to promote sperm motility with that of pentoxifylline and sildenafil. After seminal plasma was discarded, several semen samples were subjected to four treatments (control, PF-2545920, pentoxifylline, and sildenafil) to evaluate their ability to affect motility, viability, and spontaneous acrosome reactions. Intracellular calcium and adenosine triphosphate (ATP), mitochondrial membrane potential, and penetration through viscous medium were assessed by flow cytometry, luciferase, and hyaluronic acid after treatment with PF-2545920. Statistical analyses were performed using the analysis of variance statistical test. PF-2545920 elevated the percentage of motile spermatozoa compared to the control, pentoxifylline, and sildenafil groups at 10 µmol l -1 ( P < 0.01). It is less toxic to GC-2spd mouse spermatocytes cells and spermatozoa and causes fewer spontaneous acrosomal reactions ( P < 0.05). PF-2545920 also increased mitochondrial membrane potential ( P < 0.001) and altered intracellular calcium ( P < 0.05) in a dose-dependent manner, including increasing sperm hyaluronic acid penetrating ability ( P < 0.05). Therefore, PF-2545920 might be an excellent choice for stimulating the sperm motility.

Enhanced hydrogen evolution activity of CsPbBr3 nanocrystals achieved by dimensionality change.

Dimensionality plays a vital role at the nanoscale in tuning the electronical and photophysical properties and surface features of perovskite nanocrystals. Here, 3D and 1D all-inorganic CsPbBr3 nanocrystals were chosen as model materials to systemically reveal the dimensionality-dependent effect in photocatalytic H2 evolution. In terms of facilitating photoinduced electron-hole pair separation and charge transfer, as well as inducing proton reduction potential with the presence of fewer Br vacancies, 1D CsPbBr3 nanorods gave about a 5-fold improvement for solar H2 evolution.

Fe-Catalyzed Alkylazidation of α-Trifluoromethylalkenes: An Access to Quaternary Stereocenters Containing CF3 and N3 Groups.

A concise Fe-catalyzed alkylazidation of α-trifluoromethylalkenes via a C-C bond cleavage/radical addition/azidation cascade is described. This protocol features a broad substrate scope, excellent functional group compatibility, and the ability to be performed on a gram scale, thus offering a practical and step-economic approach to the synthetically useful tertiary α-trifluoromethyl azides.

Tigliane-and daphnane-type diterpenoids from the buds of Daphne genkwa with their cytotoxic activities.

Two new tigliane- and daphnane-type diterpenoids, given the trivial names daphnegens A-B (1-2) were isolated from the buds of Daphne genkwa. Their structures were assigned on the basis of extensive spectroscopic. The absolute configurations of both compounds were determined by comparison of their calculated and experimental CD curves. In addition, compounds 1-2 were tested for their cytotoxic activities against MCF-7 and HepG-2 human cancer cell lines, and compound 2 showed remarkable cytotoxic activity against HepG-2 cell line with the IC50 value of 11.5 µM.

Analysis of 50 cases of bloodstream infection with Listeria monocytogenes / 中国热带医学

@#Abstract: Objective　To analyze the characteristics of bloodstream infection of Listeria monocytogenes and provide basis for the diagnosis and treatment of the disease. Methods　We retrospectively analyzed the cases of Listeria monomyrhosi bloodstream infection in Peking Union Medical College Hospital (PUMCH) from April 2012 to April 2022. The age, sex, onset time, underlying disease, symptoms, diagnosis, treatment and prognosis of the patients were analyzed, as well as the changes of white blood cells (WBC), neutrophils, lymphocytes, and C-reactive protein (CRP) before and after anti-infection treatment. Results　Fifty cases of Listeria monocytogenes bloodstream infection confirmed by blood culture were involved. The age of patients ranged from 0 to 82 (43.7±20.0) years old, among whom 20.0% were over 60 years old. The onset time of patients was the highest in spring (44.0%), followed by winter (24.0%), and relatively fewer in summer and autumn (14.0%-18.0%). The median diagnosis time was 3 days (1-60 days). After the etiological diagnosis, 45 patients (90.0%) had underlying diseases or pregnancy status, and 45 patients were adjusted to the target antibacterial treatment mainly with carbapenems (48.9%) and penicillins (44.4%). The level of WBC, neutrophils, lymphocytes, monocytes, and CRP after treatment were significantly lower than those pre-treatments (P<0.05). Among all patients, 36 cases (72.0%) were treated according to the Antimicrobial Treatment Guidelines for Fever Sanford, of which 26 cases (72.2%) were discharged from the hospital, two cases died, one case was transferred to other hospitals, and 7 cases had a poor prognosis. Conclusions　Autoimmune diseases, tumor diseases, pregnant patients are susceptible to Listeria monocytogenes infection. Penicillins are the first choice for effective empiric therapy. For the patients allergic to penicillins, trimethoprim/sulfamethoxazole or meropenem could be used.

Switchable In Situ SO2 Capture and CF3 Migration of Enol Triflates with Peroxyl Compounds under Iron Catalysis.

Switchable in situ SO2 capture and CF3 migration of enol triflates with peroxyl compounds under iron catalysis are presented. By regulating the structure of peroxides, a variety of keto-functionalized dialkyl sulfones and α-trifluoromethyl ketones were selectively synthesized in good yields under mild conditions.

[Silk fibroin/collagen composite hydrogels with different matrix stiffness influence the growth and phenotype of human mammary epithelial cells].

Extracellular matrix (ECM) stiffness is closely related to the physiological and pathological states of breast tissue. The current study was aimed to investigate the effect of silk fibroin/collagen composite hydrogels with adjustable matrix stiffness on the growth and phenotype of normal breast epithelial cells. In this study, the enzymatic reaction of horseradish peroxidase (HRP) with hydrogen peroxide (H2O2) was used to change the degree of cross-linking of the silk fibroin solution. The rotational rheometer was used to characterize the composite hydrogel's biomechanical properties. Human normal mammary epithelial cell line MCF-10A were inoculated into composite hydrogels with various stiffness (19.10-4 932.36 Pa) to construct a three dimensional (3D) culture system of mammary epithelial cells. The CCK-8 assay was applied to detect the cell proliferation rate and active states in each group. Hematoxylin-Eosin (HE) staining and whole-mount magenta staining were used for histological evaluation of cell morphology and distribution. The results showed that with the increase of matrix stiffness, MCF-10A cells exhibited inhibited proliferation rate, decreased formation of acinus structures and increased branching structures. Meanwhile, with the increase of matrix stiffness, the polarity of MCF-10A cells was impeded. And the increase of matrix stiffness up-regulated the expression levels of mmp-2, mmp-3, and mmp-9 in MCF-10A cells. Among the genes related to epithelial-mesenchymal transition (EMT), the expression level of the epithelial marker gene E-cadherin was significantly down-regulated, while the interstitial cell marker gene Vimentin was up-regulated, and the expression levels of Snail, Wnt5b and Integrin ß1 in the Wnt pathway were up-regulated. These results suggest that the silk fibroin/collagen composite hydrogels with adjustable matrix stiffness regulates the proliferation and the phenotype of MCF-10A cells. The effects of increased matrix stiffness may be closely related to the changes of the polar structures and function of MCF-10A cells, as well as the occurrence of ECM-remodeling and EMT.

[Illness cognition and related factors in patients with prostate cancer].

OBJECTIVE: To study the illness cognition and related factors in patients with prostate cancer (PCa). METHODS: Using the convenience-sampling method, we selected 231 PCa patients treated in a general hospital in Xuzhou from October 2019 to October 2020. We conducted a cross-sectional study of the cases based on the general data of the patients and their scores on the Illness Cognition Questionnaire (ICQ). RESULTS: The PCa patients showed a high negative and a low positive illness cognition. The ICQ scores of the patients were high on "helplessness" (13.70 ± 3.54) and low on "acceptance" (16.64 ± 3.37) and "perceived benefits" (13.93 ± 3.76). Age, disease duration, disease stage and number of children were the four factors included in the regression equation of the participants' illness cognition. CONCLUSION: Negative illness cognition is high in PCa patients, higher in those at a younger age, with a longer disease duration, or with more than one child than in those at an older age, with a shorter disease duration, or with only one or no child.