[Value of complement component 3 in predicting the prognosis of children with sepsis]. / 补体C3å¯¹å„¿ç«¥è„“æ¯’ç—‡æ‚£è€ é¢„åŽçš„é¢„æµ‹ä»·å€¼.

OBJECTIVES: To investigate changes in complement component 3 (C3) levels in children with sepsis and its correlation with the severity of sepsis and to explore the significance of C3 in predicting mortality in children with sepsis. METHODS: A retrospective analysis was conducted on 529 children with sepsis who were admitted to the Pediatric Intensive Care Unit in Hunan Children's Hospital between November 2019 and September 2021. The children were categorized into two groups based on their prognosis at day 28 after sepsis diagnosis: the survival group (n=471) and the death group (n=58). Additionally, the children were divided into normal C3 group (n=273) and reduced C3 group (n=256) based on the median C3 level (0.77 g/L) within 24 hours of admission. Clinical data and laboratory markers were compared between the groups, and assess the predictive value of C3 levels in relation to sepsis-related mortality. RESULTS: The death group exhibited significantly lower C3 levels compared to the survival group (P<0.05). Multivariate logistic regression analysis revealed that higher pediatric Sequential Organ Failure Assessment (p-SOFA) scores and lower C3 levels were closely associated with sepsis-related mortality (P<0.05). The receiver operating characteristic curve (ROC) analysis demonstrated that combination of p-SOFA scores and C3 levels yielded an area under the ROC curve of 0.852, which was higher than that of each indicator alone (P<0.05). CONCLUSIONS: C3 can serve as an indicator to assess the severity and prognosis of sepsis in children. The combination of p-SOFA scores and C3 levels holds good predictive value for mortality in children with sepsis.

Difluoromethylation of Unactivated Alkenes Using Freon-22 through Tertiary Amine-Borane-Triggered Halogen Atom Transfer.

The application of abundant and inexpensive fluorine feedstock sources to synthesize fluorinated compounds is an appealing yet underexplored strategy. Here, we report a photocatalytic radical hydrodifluoromethylation of unactivated alkenes with an inexpensive industrial chemical, chlorodifluoromethane (ClCF2H, Freon-22). This protocol is realized by merging tertiary amine-ligated boryl radical-induced halogen atom transfer (XAT) with organophotoredox catalysis under blue light irradiation. A broad scope of readily accessible alkenes featuring a variety of functional groups and drug and natural product moieties could be selectively difluoromethylated with good efficiency in a metal-free manner. Combined experimental and computational studies suggest that the key XAT process of ClCF2H is both thermodynamically and kinetically favored over the hydrogen atom transfer pathway owing to the formation of a strong boron-chlorine (B-Cl) bond and the low-lying antibonding orbital of the carbon-chlorine (C-Cl) bond.

Asymmetric Synthesis of a Potent HIV-1 Integrase Inhibitor.

The development of a practical asymmetric total synthesis of the potent HIV-1 integrase inhibitor 5 is described. Key transformations include construction of the naphthridine core in a highly efficient manner followed by cyclization of the 8-membered ring. Control of the atropisomers of intermediates and final compound 5 is also described.

Rapid fluorescent detection of Escherichia coli K88 based on DNA aptamer library as direct and specific reporter combined with immuno-magnetic separation.

Nucleic acid aptamers have long demonstrated the capacity to bind cells with high affinity so that they have been utilized to diagnose various important pathogens. In this study, a DNA aptamer library was on initial efforts developed to act as a specific reporter for rapid detection of enter toxigenic Escherichia coli (ETEC) K88 combined with immuno-magnetic separation (IMS). During a Whole-cell Systematic Evolution of Ligands by Exponential Enrichment (CELL-SELEX) procedure, the last selection pool against ETEC K88, which is named "DNA aptamer library" here, was selected and subsequently identified by flow cytometric analysis and confocal imaging. A K88 monoclonal antibody (mAb) with high affinity (K(aff): 1.616 ± 0.033 × 10(8) M(-1)) against K88 fimbrial protein was prepared, biotinylated and conjugated to streptavidin-coated magnetic beads (MBs). After the bacteria were effectively captured and enriched from the complex sample by immuno-magnetic beads (IMBs), 5'-FITC modified aptamer library was directly bound to target cells as a specific reporter for its detection. The detection system showed clearly high specificity and sensitivity with the detection limit of 1.1 × 10(3) CFU/ml in pure culture and 2.2 × 10(3) CFU/g in artificially contaminated fecal sample. The results also indicated that fluorophore-lablled DNA aptamer library as specific reporter could generate more reliable signals than individual aptamer with best affinity against target cells and implied it would have great applied potential in directly reporting bacteria from complex samples combined with IMS technology.

Highly specific and cost-efficient detection of Salmonella Paratyphi A combining aptamers with single-walled carbon nanotubes.

In this paper, a panel of single-stranded DNA aptamers with high affinity and specificity against Salmonella Paratyphi A was selected from an enriched oligonucleotide pool by a whole-cell-Systematic Evolution of Ligands by Exponential Enrichment (SELEX) procedure, during which four other Salmonella serovars were used as counter-selection targets. It was determined through a fluorescence assay that the selected aptamers had high binding ability and specificity to this pathogen. The dissociation constant of these aptamers were up to nanomolar range, and aptamer Apt22 with the lowest Kd (47 ± 3 nM) was used in cell imaging experiments. To detect this bacteria with high specificity and cost-efficiently, a novel useful detection method was also constructed based on the noncovalent self-assembly of single-walled carbon nanotubes (SWNTs) and DNAzyme-labeled aptamer detection probes. The amounts of target bacteria could be quantified by exploiting chemoluminescence intensity changes at 420 nm and the detection limit of the method was 103 cfu/mL. This study demonstrated the applicability of Salmonella specific aptamers and their potential for use in the detection of Salmonella in food, clinical and environmental samples.

The synergistic effect of digital economy and manufacturing structure upgrading on carbon emissions reduction: Evidence from China.

Promoting the integration of the digital economy with the manufacturing-based real economy is beneficial to avoid the detachment of economic development from tangible industries. Whether the low-carbon transformation can be achieved in this integration process is also an important issue. So, taking China for instance, we theoretically analyze the impact mechanism of the integration of the digital economy with three major categories of manufacturing (labor-intensive, capital-intensive, and technology-intensive) on carbon emissions, and empirically test those effects based on 30 provinces in China from 2011 to 2019. The following conclusions are drawn: (1) The development of the digital economy can reduce carbon emissions. (2) The integration of the digital economy with different categories within the manufacturing industry causes different effects on carbon emissions reduction, shown as a structural upgrading type of carbon emissions reduction, i.e., the deeper integration between digital economy and technology-intensive manufacturing contributes to a multiplier effect in carbon emissions reduction. (3) The efficiency improvements benefited from the integration with the digital economy in technology-intensive manufacturing are the main reason for the structural upgrading type of carbon emissions reduction. Therefore, policy should aim at accelerating the integration of the digital economy with advanced manufacturing to realize comprehensive low-carbon transformation.

Photoinduced Defluorinative Branch-Selective Olefination of Multifluoro (Hetero)arenes.

We report a photoredox platform for constructing styrenyl polyfluoro (hetero)arenes with branch selectivity by taking advantage of sulfinate as both a radical-relay precursor and a sacrificial nucleofuge. This protocol merges photoredox catalysis with radical-radical coupling and an elimination process in a one-pot operation and features good functional group tolerance, mild conditions, and a facile method to access polyfluoro (hetero)aryl derivatives of natural products and drugs.

Programmable synthesis of difluorinated hydrocarbons from alkenes through a photocatalytic linchpin strategy.

The introduction of difluoromethylene moieties into organic molecules has garnered significant attention due to their profound influence on the physicochemical and biological properties of compounds. Nonetheless, the existing approaches for accessing difluoroalkanes from readily available feedstock chemicals remain limited. In this study, we present an efficient and modular protocol for the synthesis of difluorinated compounds from alkenes, employing the readily accessible reagent, ClCF2SO2Na, as a versatile "difluoromethylene" linchpin. By means of an organophotoredox-catalysed hydrochlorodifluoromethylation of alkenes, followed by a ligated boryl radical-facilitated halogen atom transfer (XAT) process, we have successfully obtained various difluorinated compounds, including gem-difluoroalkanes, gem-difluoroalkenes, difluoromethyl alkanes, and difluoromethyl alkenes, with satisfactory yields. The practical utility of this linchpin strategy has been demonstrated through the successful preparation of CF2-linked derivatives of complex drugs and natural products. This method opens up new avenues for the synthesis of structurally diverse difluorinated hydrocarbons and highlights the utility of ligated boryl radicals in organofluorine chemistry.

Early Clinical Development of Lufotrelvir as a Potential Therapy for COVID-19.

Lufotrelvir was designed as a first in class 3CL protease inhibitor to treat COVID-19. Development of lufotrelvir was challenged by its relatively poor stability due to its propensity to epimerize and degrade. Key elements of process development included improvement of the supply routes to the indole and lactam fragments, a Claisen addition to homologate the lactam, and a subsequent phosphorylation reaction to prepare the prodrug as well as identification of a DMSO solvated form of lufotrelvir to enable long-term storage. As a new approach to preparing the indole fragment, a Cu-catalyzed C-O coupling using oxalamide ligands was demonstrated. The control of process-related impurities was essential to accommodate the parenteral formulation. Isolation of an MEK solvate followed by the DMSO solvate ensured that all impurities were controlled appropriately.

Correlation of IgH-CDR3 Immune Repertoire Diversity Test in Peripheral Blood of Neuromyelitis Spectrum Diseases.

Neuroretinitis spectrum disorder (NMOSD) is generally regarded as an acute or subacute inflammatory demyelinating disease of the central nervous system, mainly involving the optic nerve and spinal cord, mediated by humoral immunity. To address these questions, this work established an immunomic library of the heavy chain complementarity determinant 3 (gHI-CDR3) of peripheral blood lymphocyte B cell receptors. The library was established in patients with a spectrum of neurosyphilis-retinitis disorders. Six NMOSD patients and six healthy volunteers were recruited, and the NMOSD group was divided into an early-onset group and a stable group according to treatment conditions. The IgH-CDR3 gene fragment cultured in vitro was amplified by multiplex PCR technology, and the gene was sequenced by the second-generation high-throughput sequencing technology, and the statistical analysis was carried out by the method without reference. The quantity, type, and diversity of IgH-CDR3 in peripheral blood B lymphocytes of NMOSD patients were significantly lower than those of normal group (P > 0.05); the variation of IgH-CDR3 sequence in the initial stage of treatment was higher than that in the stable stage (P > 0.05); the replication frequency of the characteristic gene "CASSICLGSGCGGYYYGMDVW" was significantly increased in patients at the initial stage of NMOSD treatment (P < 0.05). The conclusion was that the gene expression and gene expression analysis of NMOSD patients could accurately judge the condition of NMOSD patients, evaluate their efficacy, and provide new molecular targets and new theoretical basis for clinical application.

[Research progress on the role of nuclear factor erythroid 2-related factor 2 in ferroptosis of sepsis].

Sepsis is a life-threatening organ dysfunction caused by the disorder of the body's response to infection, and is one of the main causes of death in critically ill patients. Ferroptosis is a kind of iron dependent cell death, characterized by intracellular reactive oxygen species (ROS) accumulation. Sepsis can cause a substantial accumulation of ROS in cells. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of antioxidant and plays a critical protective role in sepsis induced ferroptosis by regulating the expression of proteins related to the ferroptosis pathway. Current studies have found that activation of Nrf2 has a protective effect on ferroptosis induced by sepsis. In this paper, we summarized the regulation mechanism of Nrf2 in ferroptosis, in order to provide references for the treatment of sepsis.

Synthesis of vaniprevir (MK-7009): lactamization to prepare a 20-membered [corrected] macrocycle.

Development of a practical synthesis of MK-7009, a 20-membered [corrected] macrocycle, is described. A variety of ring-closing strategies were evaluated, including ring-closing metathesis, intermolecular palladium-catalyzed cross-couplings, and macrolactamization. Ring closure via macrolactamization was found to give the highest yields under relatively high reaction concentrations. Optimization of the ring formation step and the synthesis of key intermediates en route to MK-7009 are reported.

Junction fabrication by shadow evaporation without a suspended bridge.

We present a novel shadow evaporation technique for the realization of junctions and capacitors. The design by e-beam lithography of strongly asymmetric undercuts on a bilayer resist enables in situ fabrication of junctions and capacitors without the use of the well-known suspended bridge (Dolan 1977 Appl. Phys. Lett. 31 337-9). The absence of bridges increases the mechanical robustness of the resist mask as well as the accessible range of the junction size, from 10(-2) µm(2) to more than 10(4) µm(2). We have fabricated Al/AlO(x)/Al Josephson junctions, phase qubit and capacitors using a 100 kV e-beam writer. Although this high voltage enables a precise control of the undercut, implementation using a conventional 20 kV e-beam is also discussed. The phase qubit coherence times, extracted from spectroscopy resonance width, Rabi and Ramsey oscillation decays and energy relaxation measurements, are longer than the ones obtained in our previous samples realized by standard techniques. These results demonstrate the high quality of the junction obtained by this bridge-free technique.

Aptamer selection for the detection of Escherichia coli K88.

In this study, the first group of single-stranded DNA aptamers that are highly specific to enterotoxigenic Escherichia coli (ETEC) K88 was obtained from an enriched oligonucleotide pool by the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) procedure, during which the K88 fimbriae protein was used as the target and bovine serum albumin as counter targets. These aptamers were applied successfully in the detection of ETEC K88. They were then grouped under different families based on the similarity of their secondary structure and the homology of their primary sequence. Four sequences from different families were deliberately chosen for further characterization by fluorescence analysis. Having the advantage of high sensitivity, fluorescence photometry was selected as single-stranded DNA quantification method during the SELEX process. Aptamers with the highest specificity and affinity were analyzed to evaluate binding ability with E. coli. Since ETEC K88 is the only type of bacterium that expressed abundant K88 fimbriae, the selected aptamers against the K88 fimbriae protein were able to specifically identify ETEC K88 among other bacteria. This method of detecting ETEC K88 by aptamers can also be applied to bacteria other than ETEC K88.

Detection of bifidobacterium species-specific 16S rDNA based on QD FRET bioprobe.

Fluorescence resonance energy transfer (FRET) that consists of quantum dot as donors and organic fluorophore dyes as acceptors has been a very important method to detect biomolecules such as nucleic acids. In this work, we established a new FRET detection system of Bifidobacterium species-specific 16S rDNA using QD-ROX FRET bioprobe, in which 525 nm QD-DNA conjugation consisted of the carboxyl-modified QD and the amino-modified DNA in the presence of EDC. Both ROX-DNA and the conjugation above could hybridize with the target DNA after forming the QD-ROX bioprobe. When the hybridization made the distance between the QD and ROX to meet FRET effect needed, 525 nm QD fluorescence intensity decreased and ROX fluorescence intensity increased. In the control, there was no notable change of fluorescence intensities without target DNA. It is very clear that the change of the QD and ROX fluorescence intensities provide the good base and guaranty for this rapid and simple detection system.

A new method for the detection of ATP using a quantum-dot-tagged aptamer.

Fluorescence resonance energy transfer (FRET) between a quantum dot as donor and an organic fluorophore as acceptor has been widely used for detection of nucleic acids and proteins. In this paper, we developed a new method, characterized by 605-nm quantum dot (605QD) fluorescence intensity increase and corresponding Cy5 fluorescence intensity decrease, to detect adenosine triphosphate (ATP). The new method involved the use of three different oligonucleotides: 3'-biotin-modified DNA that binds to streptavidin-conjugated 605QD; 3'-Cy5-labelled DNA; and a capture DNA consisting of an ATP aptamer and a sequence which could hybridize with both 3'-biotin-modified DNA and 3'-Cy5-labelled DNA. In the absence of the target ATP, the capture DNA binds to 3'-biotin-modified DNA and 3'-Cy5-labelled DNA, bringing quantum dot and Cy5 into close proximity for greater FRET efficiency. When ATP is introduced, the release of the 3'-Cy5-labelled DNA from the hybridization complex took place, triggering 605QD fluorescence intensity increase and corresponding Cy5 fluorescence intensity decrease. Taken together, the virtue of FRET pair 605QD/Cy5 and the property of aptamer-specific conformation change caused by aptamer-ATP interaction, combined with the fluorescence intensity change of both 605QD and Cy5, provide prerequisites for simple and convenient ATP detection.

A novel technology for biosorption and recovery hexavalent chromium in wastewater by bio-functional magnetic beads.

The goal of this study was to develop an applied technique for the removal and recovery of heavy metal in wastewater. It is novel that the Cr(VI) could be adsorbed and recovered by bio-functional magnetic beads. Furthermore, the magnetic separation technology would make their separation more convenient. The beads were constituted by the powder of Rhizopus cohnii and Fe(3)O(4) particles coated with alginate and polyvinyl alcohol (PVA). The parameters effecting Cr(VI) removal were obtained: the optimum pH 1.0 and optimum temperature 28 degrees C. The biosorption took place mainly in form of Cr(VI) and R. cohnii biomass played a key role in Cr(VI) adsorption. The model of Langmuir isotherm and Lagergren could be better used to fit the sorption process and kinetics, respectively. The beads still maintained predominant characteristics of adsorption, recovery and magnetism after five cycles for adsorption-desorption. The mechanism of adsorption was gained by Fourier transform infrared spectroscopy (FTIR), raman spectroscopy (RS) and scanning electron microscopy (SEM). The groups of -NH(3)(+), -NH(2)(+)-, and NH- played an important role in the Cr(VI) adsorption. Consequently, the beads exhibited the superior performances in Cr(VI) cleanup, separation and recovery and the perspective potential in application.

Immunomagnetic separation and MS/SPR end-detection combined procedure for rapid detection of Staphylococcus aureus and protein A.

The aim of this study was to establish an IMS-MS/SPR technique for the detection of Staphylococcus aureus (S. aureus) and Staphylococcus protein A (SPA) at the same time, which consists of isolating S. aureus and trapping-enrichmenting its SPA by IMS, and the end point is determined by using either MS or SPR measurements. Magnetic bead (MB) containing aldehyde group was synthesized with latex-polymerization and immunomagnetic bead (IMB) was fabricated by modifying its surface with an oriented layer of human IgG in covalent linkage. As soon as sample of pulverator-treated bacterial cell lysate (10(8) cfu/mL) was incubated with IMB at 4 degrees C for 30 min, SPA was captured and separated from the mixed solution in a few minutes by the IMB and then detected with mass spectrometry after washing. SPR was used to detect S. aureus quantitatively in situ at the end-detection procedure. All in all, this technique can be employed to detect rapidly SPA and S. aureus within 2h and also be applied to detect other cells or their membrane proteins with changed modified antibodies.

A highly regioselective amination of 6-aryl-2,4-dichloropyrimidine.

[reaction: see text]. A highly regioselective amination of 6-aryl-2,4-dichloropyrimidine with aliphatic secondary amines and aromatic amines has been developed which strongly favors the formation of the C4-substituted product. The reactions with aliphatic amines are carried out using LiHMDS as the base and are catalyzed by Pd, while the aromatic amines require no catalyst.

Rapid Fluorescent Detection of Enterotoxigenic Escherichia coli (ETEC) K88 Based on Graphene Oxide-Dependent Nanoquencher and Klenow Fragment-Triggered Target Cyclic Amplification.

Based on Klenow fragment (KF)-assisted target recycling amplification and graphene oxide (GO), a novel aptasensor, containing a capture probe (CP) and a signal probe (SP), was constructed and applied for the rapid detection of enterotoxigenic Escherichia coli (ETEC) K88. The CP was constructed of regions I and II, where the region I is aptamer sequence of ETEC K88 and the region II can form a double-stranded DNA structure with the SP. The SP was labeled with carboxyfluorescein (FAM) and acted as the primer sequence of the polymerization reaction. Before the targets were added, the two probes formed a partial double-strand junction (PDSJ) on the surface of the GO and the fluorescence was completely quenched. In the presence of the targets, the fluorescence was recovered due to the formation of the target-aptamer complex and its separation from the surface of the GO. Following this, the target-aptamer complex initiated the polymerization of the DNA strand in the presence of deoxynucleotides (dNTPs) and the KF. The displaced target then combined into another PDSJ, and the cycle started anew, leading to the formation of numerous complementary double-stranded DNAs. Meanwhile, the fluorescence signal was significantly enhanced. The results indicated that the established sensor has higher sensitivity specificity to its target bacteria in a wide range of 1 × 10(2) to 1 × 10(8) colony-forming units (CFU) mL(-1). The detection limit based on a signal-to-noise ratio (S/N) of 3 is 1 × 10(2) CFU mL(-1). More important, this rapid detection method is superior to other methods, having not only a short detection time but also a low fluorescence background, and is cheaper and has a wider applicability because its probes are easily designed and synthesized. Given these factors, our detection system has great prospects as a potential alternative to conventional ETEC K88 detection.