Running Wild through Dirhodium Tetracarboxylate-Catalyzed Combined CH(C)-Functionalization/Cope Rearrangement Landscapes: Does Post-Transition-State Dynamic Mismatching Influence Product Distributions?

A special type of C-H functionalization can be achieved through C-H insertion combined with Cope rearrangement (CHCR) in the presence of dirhodium catalysts. This type of reaction was studied using density functional theory and ab initio molecular dynamics simulations, the results of which pointed to the dynamic origins of low yields observed in some experiments. These studies not only reveal intimate details of the complex reaction network underpinning CHCR reactions but also further cement the generality of the importance of nonstatistical dynamic effects in controlling Rh2L4-promoted reactions.

Combined Computational and Experimental Study Reveals Complex Mechanistic Landscape of Brønsted Acid-Catalyzed Silane-Dependent P═O Reduction.

The reaction mechanism of Brønsted acid-catalyzed silane-dependent P═O reduction has been elucidated through combined computational and experimental methods. Due to its remarkable chemo- and stereoselective nature, the Brønsted acid/silane reduction system has been widely employed in organophosphine-catalyzed transformations involving P(V)/P(III) redox cycle. However, the full mechanistic profile of this type of P═O reduction has yet to be clearly established to date. Supported by both DFT and experimental studies, our research reveals that the reaction likely proceeds through mechanisms other than the widely accepted "dual activation mode by silyl ester" or "acid-mediated direct P═O activation" mechanism. We propose that although the reduction mechanisms may vary with the substitution patterns of silane species, Brønsted acid generally activates the silane rather than the P═O group in transition structures. The proposed activation mode differs significantly from that associated with traditional Brønsted acid-catalyzed C═O reduction. The uniqueness of P═O reduction originates from the dominant Si/O═P orbital interactions in transition structures rather than the P/H-Si interactions. The comprehensive mechanistic landscape provided by us will serve as a guidance for the rational design and development of more efficient P═O reduction systems as well as novel organophosphine-catalyzed reactions involving P(V)/P(III) redox cycle.

Resistin as a potential diagnostic biomarker for sepsis: insights from DIA and ELISA analyses.

PURPOSE: The primary objective of this investigation is to systematically screen and identify differentially expressed proteins (DEPs) within the plasma of individuals afflicted with sepsis. This endeavor employs both Data-Independent Acquisition (DIA) and enzyme-linked immunosorbent assay (ELISA) methodologies. The overarching goal is to furnish accessible and precise serum biomarkers conducive to the diagnostic discernment of sepsis. METHOD: The study encompasses 53 sepsis patients admitted to the Affiliated Hospital of Southwest Medical University between January 2019 and December 2020, alongside a control cohort consisting of 16 individuals devoid of sepsis pathology. Subsequently, a subset comprising 10 randomly selected subjects from the control group and 22 from the sepsis group undergoes quantitative proteomic analysis via DIA. The acquired data undergoes Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) analyses, facilitating the construction of a Protein-Protein Interaction (PPI) network to discern potential markers. Validation of core proteins is then accomplished through ELISA. Comparative analysis between the normal and sepsis groups ensues, characterized by Receiver Operating Characteristic (ROC) curve construction to evaluate diagnostic efficacy. RESULT: A total of 187 DEPs were identified through bioinformatic methodologies. Examination reveals their predominant involvement in biological processes such as wound healing, coagulation, and blood coagulation. Functional pathway analysis further elucidates their engagement in the complement pathway and malaria. Resistin emerges as a candidate plasma biomarker, subsequently validated through ELISA. Notably, the protein exhibits significantly elevated levels in the serum of sepsis patients compared to the normal control group. ROC curve analysis underscores the robust diagnostic capacity of these biomarkers for sepsis. CONCLUSION: Data-Independent Acquisition (DIA) and Enzyme-Linked Immunosorbent Assay (ELISA) show increased Resistin levels in sepsis patients, suggesting diagnostic potential, warranting further research.

Cobalt-Catalyzed Deacylative Ipso-C-C Bond Functionalization: An Approach toward Indole-Acyloins and Its Photophysical Studies.

Selective functionalization of the indole-C3-C bond with aromatic/heteroaromatic 1,2-diketones has been uncovered for the first time. Cobalt catalyst was found to be an effective catalyst for this unusual transformation. This ipso-C-C bond functionalization occurred in the presence of easily available weakly coordinating groups such as ketone and ester. One of the salient features of this methodology is the in situ generation of water from hexafluoro-2-propanol which acts as a reactant for the removal of the pivaloyl/ester group in a deacylative manner. The plausible mechanism has been supported by DFT calculations. Moreover, photophysical studies show the potential utility of indole-C3-acyloin and indolo-fused carbazole, which could be used in photovoltaic and optoelectronic application.

An electrochemical aptasensor for zearalenone detection based on the Co3O4/MoS2/Au nanocomposites and hybrid chain reaction.

An electrochemical aptasensor was used for the fast and sensitive detection of zearalenone (ZEN) based on the combination of Co3O4/MoS2/Au nanocomposites and the hybrid chain reaction (HCR). The glassy carbon electrode was coated with Co3O4/MoS2/Au nanomaterials to immobilize the ZEN-cDNA that had been bound with ZEN-Apt by the principle of base complementary pairing. In the absence of ZEN, the HCR could not be triggered because the ZEN-cDNA could not be exposed. After ZEN was added to the surface of the electrode, a complex structure was produced on the modified electrode by the combination of ZEN and ZEN-Apt. Therefore, the ZEN-cDNA can raise the HCR to produce the long-strand dsDNA structure. Due to the formation of dsDNA, the methylene blue (MB) could be inserted into the superstructure of branched DNA and the peak currents of the MB redox signal dramatically increased. So the concentration of ZEN could be detected by the change of signal intensity. Under optimized conditions, the developed electrochemical biosensing strategy showed an outstanding linear detection range of 1.0×10-10 mol/L to 1.0×10-6 mol/L, a low detection limit (LOD) of 8.5×10-11 mol/L with desirable selectivity and stability. Therefore, the fabricated platform possessed a great application potential in fields of food safety, medical detection, and drug analysis.

Thermodynamic Analysis of n-Nonadecane (C19H40)/1-Octadecanol (C18H37OH) Blends.

The article delves into the intricate phase transitions of 1-Octadecanol and n-Nonadecane within a binary system, unveiling dynamic structural changes under varying conditions. Through Fourier transform infrared (FTIR) analysis, specific molecular vibrations were identified, shedding light on the molecular composition and interactions. The study highlights the challenges in detecting subtle phase transitions and emphasises the individuality of molecular behaviours in closely related compounds. The findings underscore the complexity of phase transitions in binary systems and advocate for a nuanced approach to studying molecular structures and behaviours.

Separation techniques for manufacturing fruit spirits: From traditional distillation to advanced pervaporation process.

Separation process is one of the key processes in the production of fruit spirits, including the traditional distillation method and the new pervaporation membrane method. The separation process significantly determines the constituents and proportions of compounds in the fruit spirit, which has a significant impact on the spirit quality and consumer acceptance. Therefore, it is important and complex to reveal the changing rules of chemical substances and the principles behind them during the separation process of fruit spirits. This review summarized the traditional separation methods commonly used in fruit spirits, covering the types, principles, and corresponding equipment of distillation methods, focused on the enrichment or removal of aroma compounds and harmful factors in fruit spirits by distillation methods, and tried to explain the mechanism behind it. It also proposed a new separation technology for the production of fruit spirits, pervaporation membrane technology, summarized its working principle, operation, working parameters, and application in the production of fruit spirits, and outlined the impact of the separation method on the production of fruit spirits based on existing research, focusing on the separation of flavor compounds, sensory qualities, and hazard factors in fruit spirits, along with a preliminary comparison with distillation. Finally, according to the current researches of the separation methods and the development requirement of the separation process of fruit spirits, the prospect of corresponding research is put forward, in order to propose new ideas and development directions for the research in this field.

Borane-Catalyzed C-F Bond Functionalization of gem-Difluorocyclopropenes Enables the Synthesis of Orphaned Cyclopropanes.

Herein, we disclose an approach to synthesize tert-alkyl cyclopropanes by leveraging C-F bond functionalization of gem-difluorocyclopropenes using tris(pentafluorophenyl)borane catalysis. The reaction proceeds through the intermediacy of a fluorocyclopropenium ion, which was confirmed by the isolation of [Ph2(C6D5)C3]+[(C6F5)3BF]-. We found that silylketene acetal nucleophiles were optimal reaction partners with fluorocyclopropenium ion intermediates yielding fully substituted cyclopropenes functionalized with two α-tert-alkyl centers (63-93% yield). The regioselectivity of the addition to cyclopropenium ions is controlled by their steric and electronic properties and enables access to 3,3-bis(difluoromethyl)cyclopropenes in short order. The resulting cyclopropene products are readily reduced to the corresponding orphaned cyclopropanes under hydrogenation conditions. Quantum chemical calculations reveal the nature of the C-F bond cleavage steps and provide evidence for catalysis by boron and not silylated oxonium ions, though Si-F bond formation is the enthalpic driving force for the reaction.

A Shapeshifting Roadmap for Polycyclic Skeletal Evolution.

Polycyclic ring systems are ubiquitous three-dimensional (3D) structural motifs central to the function of many biologically active small molecules and organic materials. Indeed, subtle changes to the overall molecular shape and connectivity of atoms in a polycyclic framework (i.e., isomerism) can drastically alter its function and properties. Unfortunately, direct evaluation of these structure-function relationships typically requires the development of distinct synthetic strategies toward a specific isomer. Dynamic, "shapeshifting" carbon cages present a promising approach for sampling isomeric chemical space but are often difficult to control and are largely limited to thermodynamic mixtures of positional isomers about a single core scaffold. Here, we describe the development of a new shapeshifting C9-chemotype and a chemical blueprint for its evolution into structurally and energetically diverse isomeric ring systems. By leveraging the unique molecular topology of π-orbitals interacting through-space (homoconjugation), a common skeletal ancestor evolved into a complex network of valence isomers. This unusual system represents an exceedingly rare small molecule capable of undergoing controllable and continuous isomerization processes through the iterative use of just two chemical steps (light and organic base). Computational and photophysical studies of the isomer network provide fundamental insight into the reactivity, mechanism, and role of homoconjugative interactions. Importantly, these insights may inform the rational design and synthesis of new dynamic, shapeshifting systems. We anticipate this process could be a powerful tool for the synthesis of structurally diverse, isomeric polycycles central to many bioactive small molecules and functional organic materials.

Regiocontrol via Electronics: Insights into a Ru-Catalyzed, Cu-Mediated Site-Selective Alkylation of Isoquinolones via a C-C Bond Activation of Cyclopropanols.

A site-selective C(3)/C(4)-alkylation of N-pyridylisoquinolones is achieved by employing C-C bond activation of cyclopropanols under Ru(II)-catalyzed/Cu(II)-mediated conditions. The regioisomeric ratios of the products follow directly from the electronic nature of the cyclopropanols and isoquinolones used, with electron-withdrawing groups yielding predominantly the C(3)-alkylated products, whereas the electron-donating groups primarily generate the C(4)-alkylated isomers. Density functional theory calculations and detailed mechanistic investigations suggest the simultaneous existence of the singlet and triplet pathways for the C(3)- and C(4)-product formation. Further transformations of the products evolve the utility of the methodology thereby yielding scaffolds of synthetic relevance.

Binding mechanism of oseltamivir and influenza neuraminidase suggests perspectives for the design of new anti-influenza drugs.

Oseltamivir is a widely used influenza virus neuraminidase (NA) inhibitor that prevents the release of new virus particles from host cells. However, oseltamivir-resistant strains have emerged, but effective drugs against them have not yet been developed. Elucidating the binding mechanisms between NA and oseltamivir may provide valuable information for the design of new drugs against NA mutants resistant to oseltamivir. Here, we conducted large-scale (353.4 µs) free-binding molecular dynamics simulations, together with a Markov State Model and an importance-sampling algorithm, to reveal the binding process of oseltamivir and NA. Ten metastable states and five major binding pathways were identified that validated and complemented previously discovered binding pathways, including the hypothesis that oseltamivir can be transferred from the secondary sialic acid binding site to the catalytic site. The discovery of multiple new metastable states, especially the stable bound state containing a water-mediated hydrogen bond between Arg118 and oseltamivir, may provide new insights into the improvement of NA inhibitors. We anticipated the findings presented here will facilitate the development of drugs capable of combating NA mutations.

Experimental and Theoretical Investigation of the Synchronicity of Ambident Silyloxypyrone-Based (5 + 2) Cycloadditions.

The reaction pathway of silyloxypyrone-based (5 + 2) cycloadditions was determined to be extremely dependent on the nature of the dipolarophile. Neutral alkenes were the least reactive, whereas both electron-deficient and electron-rich dipolarophiles were more reactive, thus providing evidence for ambident oxidopyrylium intermediates. Qualitative rate studies, Hammett linear free energy relationships, and theoretical calculations combined to provide evidence for a spectrum of reactivity that passes through the borderlands of concerted and stepwise.

A sensitive electrochemical aptasensor for zearalenone detection based on target-triggered branched hybridization chain reaction and exonuclease I-assisted recycling.

Traditional methods for detecting antibiotic and mycotoxin residues rely on large-scale instruments, which are expensive and require complex sample pretreatment processes and professional operators. Although aptamer-based electrochemical sensors have the advantages of simplicity, speed, low cost, and high sensitivity, most aptamer-based sensors lack a signal amplification strategy due to their direct use of aptamers as probes, resulting in insufficient sensitivity. To solve the sensitivity problem in the electrochemical detection process, a novel electrochemical sensing strategy was established for ultrasensitive zearalenone (ZEN) detection on the basis of exonuclease I (Exo I) and branched hybridization chain reaction (bHCR) to amplify the signal. The amplification strategy showed excellent analytical performance towards ZEN with a low detection limit at 3.1×10-12 mol/L and a wide linear range from 10-11 to 10-6 mol/L. Importantly, the assay was utilized in the corn powder samples with satisfactory results, holding promising applications in food safety detection and environmental monitoring.

An efficient method for knocking out genes on the virulence plasmid of hypervirulent Klebsiella pneumoniae.

Currently, the infection of hypervirulent Klebsiella pneumoniae (hvKp) is becoming increasingly serious and the virulent mechanisms of hvKp are still not very clear. An effective gene-editing method for genes on hvKp virulence plasmid can help us reveal related virulent mechanisms. There are a few reports focusing on the methods mentioned above, however with certain limitations. In this work, we first constructed the pRE112-basing recombinant suicide plasmid to knock out or replace the genes in the hvKp virulence plasmid based on the principle of homology recombination. Results showed that the target virulent genes iucA, iucB, iroB, and rmpA2 on the hvKp virulence plasmid were scarlessly knocked out or replaced by marker genes, and mutant hvKp strains with the expected phenotypes were obtained. These indicated that we established an efficient gene-editing method for genes on hvKp virulence plasmid, which could help us explore the functions of these genes and reveal the virulent mechanisms of hvKp.

Comparison of clinical outcomes between the olecranon osteotomy approach and the Bryan-Morrey approach for total elbow arthroplasty.

BACKGROUND: This study aims to investigate the clinical efficacy of the olecranon osteotomy approach and the Bryan-Morrey approach in total elbow arthroplasty (TEA). METHODS: In this retrospective study, 49 patients with elbow disease were treated with TEA. A total of 22 patients with TEA by olecranon osteotomy approach were designated as group A, and 27 patients with TEA by Bryan-Morrey approach were designated as group B. There were 22 males and 27 females, aged 32-82 years with a mean age of 62 years. There were 44 cases of unilateral elbow joint, including 27 cases on the left elbow and 17 cases on the right elbow, and 5 cases of the bilateral elbow joint. There were 6 cases of osteoarthritis (7 elbows), 18 cases of rheumatoid arthritis (22 elbows), 14 cases of traumatic arthritis (14 elbows), 7 cases of distal humeral fractures (7 elbows), and 4 cases of elbow tuberculosis (4 elbows). For each group, we recorded the operative time, intraoperative bleeding, elbow flexion, extension, pronation, supination, postoperative complication rates, and Mayo Elbow Performance Score after surgery. RESULTS: Operative time and intraoperative bleeding were less in group A than in group B (53-120 min [70 (62.5, 78) min] vs. 64-105 min [77 (73, 87) min], and 10-200 ml [50 (20, 90) ml] vs. 5-250 ml [100 (50, 150) ml], P < .028). The elbow flexion, pronation activity, and Mayo Elbow Performance Score were higher in group A than in group B, [(121 ± 12)° vs. (112 ± 10)°, 85 (85,85)° vs. 80 (77,85)°, and (94 ± 3) points vs. (91 ± 4) points, P < .036], while elbow extension and supination activity and complication rates were not statistically significant in either group. CONCLUSION: Compared to Bryan-Morrey approach, the olecranon osteotomy approach to TEA provides adequate visualization, saves operative time and reduces bleeding, provides better flexion activity, effectively improves elbow function, and achieves satisfactory clinical outcomes.

C-H Insertion in Dirhodium Tetracarboxylate-Catalyzed Reactions despite Dynamical Tendencies toward Fragmentation: Implications for Reaction Efficiency and Catalyst Design.

Rh-catalyzed C-H insertion reactions to form ß-lactones suffer from post-transition state bifurcations, with the same transition states leading to ketones and ketenes via fragmentation in addition to ß-lactones. In such a circumstance, traditional transition state theory cannot predict product selectivity, so we employed ab initio molecular dynamics simulations to do so and provide a framework for rationalizing the origins of said selectivity. Weak interactions between the catalyst and substrate were studied using energy decomposition and noncovalent interaction analyses, which unmasked an important role of the 2-bromophenyl substituent that has been used in multiple ß-lactone-forming C-H insertion reactions. Small and large catalysts were shown to behave differently, with the latter providing a means of overcoming dynamically preferred fragmentation by lowering the barrier for the recombination of the product fragments in the grip of the large catalyst active site cavity.

Identification and genome characterization of novel parechovirus sequences from Hipposideros armiger in China.

BACKGROUND: Bats were identified as a natural reservoir of emerging and re-emerging infectious pathogens threatening human health and life. METHODS: This study collected 21 fecal samples of Hipposideros armiger in Mengla County of Xishuangbanna Prefecture Yunnan Province to combine one pool for viral metagenomic sequencing. RESULTS: Two nearly complete genomes of parechoviruses, BPeV11 and BPeV20, were sequenced. Genome analysis revealed that BPeV11 and BPeV20 follow a 3-3-4 genome layout: 5' UTR-VP0-VP3-VP1-2A-2B-2C-3A-3B-3C-3D-3' UTR. The prevalence of BPev11 and BPev20 by Nested-PCR showed that 1 of 21 fecal samples was positive. Based on amino acid identity comparison and phylogenetic analysis of P1, 2C, and 3D, BPeV11 and BPeV20 were closely related to but distinct from FPeVs. CONCLUSION: It was probably proposed to be a novel species in the genus Parechovirus of the family Picornaviridae. The isolation of BPev11 and BPev20 from H. armiger in China is the first complete genome of parechovirus isolations from bat feces of the genus Hipposideros.

Bistatic Doppler wind lidar study for wind field measurement over complex terrain.

Atmospheric wind measurement over complex terrain is of great significance. Due to the limitation of the retrieval method, a single wind lidar cannot be applied to detect the horizontally inhomogeneous wind field. Therefore, a bistatic Doppler wind lidar system is studied for meeting the requirement of wind detection over complex terrain. By analyzing the uncertainty of a synthetic wind field, the isosceles triangle is proven to be the optimal layout of the bistatic lidar system. By using the data set of Nanjing sounding data from 2015 and two typical wind field models, the detection accuracy of the bistatic lidar system is estimated. The experimental results show that the bistatic wind lidar can detect the wind field over complex terrain accurately, the wind errors are less than 1 m/s below 4 km, and the relative errors are less than 5%.

A novel model based on liquid-liquid phase separation-Related genes correlates immune microenvironment profiles and predicts prognosis of lung squamous cell carcinoma.

OBJECTIVE: The aim of the study was to construct and validate a robust prognostic model based on liquid-liquid phase separation (LLPS)-related genes in lung squamous cell carcinoma (LUSC). METHODS: The Cancer Genome Atlas dataset was used as the discovery set to identify the LLPS-related differentially expressed genes (DEGs) between LUSC and normal tissue. These DEGs were screened by the LASSO Cox regression analysis to identify the genes with nonzero coefficient, which were next included in the multivariate Cox regression analysis to construct the prediction model. The dataset GSE41271 was adopted as the validation set to verify the efficacy of the model. Enrichment analysis and the CIBERSORT were performed to illustrate potential immune mechanisms underlying the prediction model. RESULTS: A total of 48 LLPS-related genes were aberrantly expressed in LUSC. Among them, 7 genes were selected by the LASSO Cox regression analysis to construct the prediction model. Risk index (RI) was calculated according to the model for each patient. The prognosis was significantly different between the patients with high and low RI in the discovery set and the validation set (p < 0.001 and p = 0.028, respectively). The multivariate survival analysis confirmed RI as an independent prognostic factor in LUSC (in the discovery set: p < 0.001, HR = 2.643, 95% CI = 1.986-3.518; in the validation set: p = 0.042, HR = 2.144, 95% CI = 1.026-4.480). A series of pathways involving immune cells were found to be related to RI. The distribution pattern of immune cells and chemokines varied according to the value of RI. CONCLUSION: The prediction model based on LLPS-related genes was constructed and validated as a robust prognostic tool for LUSC using multiple datasets. LLPS might have an impact on LUSC through immune pathways.

Severe Case of Rickettsiosis Identified by Metagenomic Sequencing, China.

A case of Rickettsia sibirica subspecies sibirica BJ-90 infection in China was identified by metagenomic analysis of an eschar biopsy specimen and confirmed by nested PCR. Seroprevalence of spotted fever group Rickettsia was ≈17.4% among the local population. This report highlights the threat of rickettsioses to public health in the Qinghai-Tibet Plateau.