Radical Alkynylthiolation with Visible-Light-Sensitive S-Alkynylthio Sulfonates.

A novel kind of S-alkynylthio sulfonate, which can be directly activated under visible-light irradiation, has been developed for the radical addition of multiple bond systems and radical coupling with diazonium salts under photocatalyst-free conditions. This strategy features a broad substrate scope, high regioselectivity, excellent tolerance of functional groups, and the late-stage modification of drugs. Experimental and theoretical mechanistic investigations gave reasonable insight into the photolysis of S-alkynylthio sulfonates and C-S bond formation.

A novel method for synthesizing authentic SARS-CoV-2 main protease.

The SARS-CoV-2 main protease (Mpro) plays a crucial role in virus amplification and is an ideal target for antiviral drugs. Currently, authentic Mpro is prepared through two rounds of proteolytic cleavage. In this method, Mpro carries a self-cleavage site at the N-terminus and a protease cleavage site followed by an affinity tag at the C-terminus. This article proposes a novel method for producing authentic Mpro through single digestion. Mpro was constructed by fusing a His tag containing TEV protease cleavage sites at the N-terminus. The expressed recombinant protein was digested by TEV protease, and the generated protein had a decreased molecular weight and significantly increased activity, which was consistent with that of authentic Mpro generated by the previous method. These findings indicated that authentic Mpro was successfully obtained. Moreover, the substrate specificity of Mpro was investigated. Mpro had a strong preference for Phe at position the P2, which suggested that the S2 subsite was an outstanding target for designing inhibitors. This article also provides a reference for the preparation of Mpro for sudden coronavirus infection in the future.

Palladium(II)-Catalyzed Norbornene-Mediated Selective meta-C-H Silylation for the Synthesis of Arylsilanes from Primary Benzamides.

A palladium(II)-catalyzed norbornene-mediated remote selective meta-C-H silylation of primary benzamides was developed for the synthesis of arylsilanes. Such a conversion provides access to a range of arylsilanes with exclusive selectivity using norbornene (NBE) as the meta-C-H activator. The amide directing group can be detached simultaneously through C-C bond cleavage or undergo a dehydration reaction pathway to form nitriles.

The change of intimate relationship between people with Alzheimer's disease and their adult child caregivers: An interpretative phenomenological analysis.

This study aims to explore the change of intimate relationship between people with Alzheimer's disease and their adult child caregivers as the disease progresses. Twelve adult child caregivers were recruited through purposive sampling. Explanatory phenomenological analysis was conducted to analyse data collected by semi-structured in-depth interviews. This study found a dynamically changing relationship between adult child caregivers and their parents with Alzheimer's disease during care giving that evolved with the progress of the disease. The relationship was the most intimate in the middle stage of the disease for most caregivers and a new reciprocal relationship developed due to caregiving. Caregivers experienced different degrees of self-growth when providing care, though caregiver burdens were common. The positive experience and perception of caregivers were important for improving the quality of life for adult child caregivers of people with Alzheimer's disease.

N-Vinylthio Phthalimides (N-VTPs): Modular Reagents for Vinylthio AIEgen Transfer.

Novel sulfur reagents N-vinylthio phthalimides (N-VTPs) have been employed as modular reagents for vinylthiolation, enabling the construction of aggregation-induced emission (AIE)-active tetraaryldivinyl sulfides (TADVSs) and diarylvinyl sulfides (DAVSs). Notably, TADVSs with sulfur insertion to ethene stators are reported as AIE luminogens (AIEgens) for the first time, and the corresponding photophysical properties and aggregated confirmation have been detailed for the demonstration of the AIE effect. A water-soluble TADVS with a quinolinium salt was prepared for cell imaging.

Epidemiological investigation, determination of related factors, and spatial-temporal cluster analysis of wild type pseudorabies virus seroprevalence in China during 2022.

Introduction: Pseudorabies virus (PRV) is a linear DNA virus with a double-stranded structure, capable of infecting a diverse array of animal species, including humans. This study sought to ascertain the seroprevalence of Pseudorabies Virus (PRV) in China by conducting a comprehensive collection of blood samples from 16 provinces over the course of 2022. Methods: The presence of PRV gE antibodies was detected through the utilization of an enzyme-linked immunosorbent assay (ELISA) technique. Logistic regression analysis was conducted to identify potential related factors associated with the serologic status of PRV gE at the animal level. Additionally, the SaTScan 10.1 software was used to analyze the spatial and temporal clusters of PRV gE seroprevalence. Results: A comprehensive collection of 161,880 samples was conducted, encompassing 556 swine farms throughout the country. The analysis revealed that the seroprevalence of PRV gE antibodies was 12.36% (95% confidence interval [CI], 12.20% to 12.52%) at the individual animal level. However, at the swine farm level, the seroprevalence was considerably higher, reaching 46.22% (95% CI, 42.08% to 50.37%). Related factors for PRV infection at the farm level included the geographic distribution of farms and seasonal variables. Moreover, five distinct high seroprevalence clusters of PRV gE were identified across China, with the peak prevalence observed during the months of April through June 2022. Conclusion: Our findings serve as a valuable addition to existing research on the seroprevalence, related factors, and temporal clustering of PRV gE in China. Furthermore, our study provides a reference point for the development of effective strategies for the prevention and control of pseudorabies and wild virus outbreaks.

Resumption of production operations during the silent disposal period of African swine fever outbreaks: a case study.

BACKGROUND: Batch production, a widely implemented production model in large-scale pig farms, was characterized by its long-term duration, cost-effectiveness, and efficiency. Nevertheless, the recent occurrence of African swine fever (ASF) outbreaks in China has necessitated the implementation of discreet mating operations within this model, leading to disruptions in production cycles and substantial indirect losses. CASE PRESENTATION: This study implemented a novel operational procedure, which involved the division of risk areas for zone management and allowed mating operations, in 12 farms experiencing ASF outbreaks. Another 12 farms were used as a control group, employing the old procedure. Subsequently, the prognoses of both the old and new procedures were calculated and analyzed. The findings indicate that the new method resulted in an enhanced retention rate and reduced non-productive days (NPD), without impacting the positive detection rate and disposal time. Consequently, this approach significantly mitigated economic losses (p < 0.05). CONCLUSION: The efficacy of the novel procedure in mitigating the indirect economic losses stemming from ASF outbreaks, through the reduction of NPD while maintaining retention rates and disposition days, has been substantiated. This methodology has demonstrated feasibility in extensive pig farming operations and exhibits promise for broader application.

Evidence of aerosol transmission of African swine fever virus between two piggeries under field conditions: a case study.

African swine fever (ASF) is a devastating and economically significant infectious disease that has caused enormous losses in the commercial pig sector in China since 2018. The primary transmission routes of the African swine fever virus (ASFV), the causative agent of ASF, are direct pig-to-pig contact or indirect contact with virus-contaminated objects. While aerosol transmission of ASFV has been previously reported under experimental conditions, no reports have described it under field conditions. In this case study, aerosol-associated samples were collected over a monitoring period of 24 days in an ASFV-positive farm. A complete and clear chain of ASFV transmission through aerosols was observed: pigs in Room A on Day 0-aerosol in Room A on Day 6-dust of air outlets in Room A on Day 9-outdoor aerosols on Day 9-dust of air inlets in Room B on Day 15-aerosols/pigs in Room B on Day 21. Furthermore, a fluorescent powder experiment confirmed the transmission of dust from Room A to Room B. This study represents the first report providing evidence of aerosol transmission of ASFV under field conditions. Further research is needed to study the laws of aerosol transmission in ASFV and develop effective strategies such as air filtration or disinfection to create a low-risk environment with fresh air for pig herds.

Hierarchical Synergistic Structure for High Resolution Strain Sensor with Wide Working Range.

Strain sensors have been attracting tremendous attention for the promising application of wearable devices in recent years. However, the trade-off between high resolution, high sensitivity, and broad detection range is a great challenge for the application of strain sensors. Herein, a novel design of hierarchical synergistic structure (HSS) of Au micro cracks and carbon black (CB) nanoparticles is reported to overcome this challenge. The strain sensor based on the designed HSS exhibit high sensitivity (GF > 2400), high strain resolution (0.2%) even under large loading strain, broad detection range (>40%), outstanding stability (>12000 cycles), and fast response speed simultaneously. Further, the experiments and simulation results demonstrate that the carbon black layer greatly changed the morphology of Au micro-cracks, forming a hierarchical structure of micro-scale Au cracks and nano-scale carbon black particles, thus enabling synergistic effect and the double conductive network of Au micro-cracks and CB nanoparticles. Based on the excellent performance, the sensor is successfully applied to monitoring tiny signals of the carotid pulse during body movement, which illustrates the great potential in the application of health monitoring, human-machine interface, human motion detection, and electronic skin.

Hydroxyphenylpyruvate Dioxygenase Is a Metabolic Immune Checkpoint for UTX-deficient Colorectal Cancer.

BACKGROUND & AIMS: Aberrant epigenetic events mediated by histone methyltransferases and demethylases contribute to malignant progression of colorectal cancer (CRC). However, the role of the histone demethylase ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) in CRC remains poorly understood. METHODS: UTX conditional knockout mice and UTX-silenced MC38 cells were used to investigate UTX function in tumorigenesis and development of CRC. We performed time of flight mass cytometry to clarify the functional role of UTX in remodeling immune microenvironment of CRC. To investigate metabolic interaction between myeloid-derived suppressor cells (MDSCs) and CRC, we analyzed metabolomics data to identify metabolites secreted by UTX-deficient cancer cells and taken up by MDSCs. RESULTS: We unraveled a tyrosine-mediated metabolic symbiosis between MDSC and UTX-deficient CRC. Loss of UTX in CRC resulted in methylation of phenylalanine hydroxylase, preventing its degradation and subsequently increasing tyrosine synthesis and secretion. Tyrosine taken up by MDSCs was metabolized to homogentisic acid by hydroxyphenylpyruvate dioxygenase. Homogentisic acid modified protein inhibitor of activated STAT3 via carbonylation of Cys 176, and relieved the inhibitory effect of protein inhibitor of activated STAT3 on signal transducer and activator of transcription 5 transcriptional activity. This in turn, promoted MDSC survival and accumulation, enabling CRC cells to acquire invasive and metastatic traits. CONCLUSIONS: Collectively, these findings highlight hydroxyphenylpyruvate dioxygenase as a metabolic checkpoint to restrict immunosuppressive MDSCs and to counteract malignant progression of UTX-deficient CRC.

Treatment planning consideration for very high-energy electron FLASH radiotherapy.

PURPOSE: Very high-energy electron (VHEE) can make up the insufficient treatment depth of the low-energy electron while offering an intermediate dosimetric advantage between photon and proton. Combining FLASH with VHEE, a quantitative comparison between different energies was made, with regard to plan quality, dose rate distribution (both in PTV and OAR), and total duration of treatment (beam-on time). METHODS: In two patient cases (head and lung), we created the treatment plans utilizing the scanning pencil beam via the Monte Carlo simulation and a PTV-based optimization algorithm. Geant4 was used to simulate VHEE pencil beams and sizes of 0.3-5 mm defined by the full width at half maximum (FWHM). Monoenergetic beams with Gaussian distribution in x and y directions (ISOURC = 19) were used as the source of electrons. A large-scale non-linear solver (IPOPT) was used to calculate the optimal spot weights. After optimization, a quantitative comparison between different energies was made regarding treatment plan quality, dose rate distribution (both in PTV and OAR), and total beam duration. RESULTS: For head (80 MeV, 100 MeV, and 120 MeV) and lung cases (100 MeV, 120 MeV, and 140 MeV), the minimum beam intensity needs to be ∼2.5 × 1011 electrons/s and ∼9.375 × 1011 electrons/s to allow > 90 % volume of PTV reaching the average dose rate (DADR) higher than 40 Gy/s. At this beam intensity (fraction dose: 10 Gy), the overall irradiation time for the head case is 5258.75 ms (80 MeV), 5149.75 ms (100 MeV), and 4976.75 ms (120 MeV), including scanning time 872.75 ms. For lung cases, this number is 1034.25 ms (100 MeV), 981.55 ms (120 MeV), and 928.15 ms (140 MeV), including scanning time 298.75 ms. The plan of higher energy always performs with a higher dose rate (both in PTV and OAR) and thereby costs less delivery time (beam-on time). CONCLUSION: The study systematically investigated the currently known FLASH parameters for VHEE radiotherapy and successfully established a benchmark reference for its FLASH dose rate performance.

Optimization of the expression of the main protease from SARS-CoV-2.

The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a vital role in viral replication. To study the function of Mpro and screen inhibitors targeting Mpro, it is necessary to prepare high-purity and high-activity Mpro. In this study, four types of SARS-CoV-2 Mpros containing different termini were prepared, and their activities were determined successfully. The results showed that the activity of wild-type (WT) Mpro was the highest, and the additional residues at the N-terminus but not at the C-terminus had a major effect on the enzyme activity. To explain this, the alignment of structures of different forms of Mpro was determined, and the additional residues at the N-terminus were found to interfere with the formation of the substrate binding pocket. This study confirms the importance of the natural N-terminus to the activity of Mpro and suggests that WT-GPH6 (Mpro with eight additional residues at the C-terminus) can be used as a substitute for authentic Mpro to screen inhibitors. In short, this study provides a reference for the expression and purification of new coronaviruses confronted in the future.

Homocouplings of Sodium Arenesulfinates: Selective Access to Symmetric Diaryl Sulfides and Diaryl Disulfides.

Symmetrical diaryl sulfides and diaryl disulfides have been efficiently and selectively constructed via the homocoupling of sodium arenesulfinates. The selectivity of products relied on the different reaction systems: symmetrical diaryl sulfides were predominately obtained under the Pd(OAc)2 catalysis, whereas symmetrical diaryl sulfides were exclusively yielded in the presence of the reductive Fe/HCl system.

Inguinal lymph node sample collected by minimally invasive sampler helps to accurately diagnose ASF in dead pigs without necropsy.

African swine fever (ASF) is a highly contagious hemorrhagic and transboundary animal disease, and it threatens global food security. A full necropsy to harvest the sample matrices for diagnosis in the farm may lead to contamination of the premises and directly threaten to the herds. In the present study, we compared the ASFV loads of the common samples that can be collected without necropsy. The unmatched nasal, throat, rectal samples were randomly taken using cotton swabs, and inguinal lymph node samples were collected by the minimally invasive samplers from the dead pigs of an ASF field outbreak farm. The ASFV loads of the samples were detected by qPCR and the results suggested that the overall ASFV nucleic acids levels of inguinal lymph node samples were higher than the swabs. What's more, sets of matched nasal swabs, rectal swabs, throat swabs, inguinal lymph nodes, serums, spleens and lungs samples were collected from 15 dead ASFV naturally infected pigs. Similarly, the results showed that inguinal lymph node samples, together with serum, spleen and lungs samples, contained more ASFV nucleic acids than the swabs. Our findings demonstrated that the inguinal lymph node collected by minimally invasive sampler is an ideal tissue for diagnosing ASFV infection in dead pigs without necropsy.

Divergent Synthesis of Fluorinated Alkenes, Allenes, and Enynes via Reaction of 2-Trifluoromethyl-1,3-enynes with Carbon Nucleophiles.

Herein, inorganic base K3PO4 promoted divergent synthesis of CF3-substituted allenes, cyclopentenes, alkynes, and fluorinated enynes via regioselective nucleophilic addition of carbon nucleophiles to 2-trifluoromethyl-1,3-enynes was developed. With the choice of different carbon nucleophiles, various fluorinated compounds could be obtained under K3PO4/DMF reaction system. When malononitriles were used as nucleophiles, CF3-substituted allenes, cyclopentenes, and alkynes could be obtained, respectively. By using 1,3-dicarbonyl compounds as nucleophiles, ring-monofluorinated 4H-pyrans could be prepared, and 1,1-difluoro-1,3-enynes could be furnished with the participation of diethyl malonate. Moreover, these five kinds of fluorinated allenes, alkenes, and enynes are valuable building blocks.

Research on Named Entity Recognition Based on Multi-Task Learning and Biaffine Mechanism.

Commonly used nested entity recognition methods are span-based entity recognition methods, which focus on learning the head and tail representations of entities. This method lacks obvious boundary supervision, which leads to the failure of the correct candidate entities to be predicted, resulting in the problem of high precision and low recall. To solve the above problems, this paper proposes a named entity recognition method based on multi-task learning and biaffine mechanism, introduces the idea of multi-task learning, and divides the task into two subtasks, entity span classification and boundary detection. The entity span classification task uses biaffine mechanism to score the resulting spans and select the most likely entity class. The boundary detection task mainly solves the problem of low recall caused by the lack of boundary supervision in span classification. It captures the relationship between adjacent words in the input text according to the context, indicates the boundary range of entities, and enhances the span representation through additional boundary supervision. The experimental results show that the named entity recognition method based on multi-task learning and biaffine mechanism can improve the F1 value by up to 7.05%, 12.63%, and 14.68% on the GENIA, ACE2004, and ACE2005 nested datasets compared with other methods, which verifies that this method has better performance on the nested entity recognition task.

In Situ Generated UiO-66/Cotton Fabric Easily Recyclable for Reactive Dye Adsorption.

In view of the environmental pollution caused by the widespread use of reactive dyes in the printing and dyeing industry, the modified cotton fabric was loaded with the extremely stable metal-organic frame (MOF) material UiO-66 for removing reactive dyes from colored wastewater. UiO-66/cotton fabric was prepared by in situ synthesis, and its surface morphology and structure were analyzed by XRD, SEM, BET, and XPS. The adsorption performance of UiO-66/cotton fabric on reactive dyes was investigated by adsorbent dosage, adsorption time and temperature, dye concentration, pH, and so on. The results indicated that the adsorption equilibrium time of UiO-66/cotton fabric on reactive orange 16 was 120 min, and the removal rate was about 98%. The adsorption process belongs to simple molecular layer chemisorption and can be regarded as a spontaneous heat absorption reaction, which was consistent with the proposed secondary kinetic model and Langmuir isothermal adsorption model. In addition, the reactive dyes with a higher molecular weight of each sulfonic acid group are more hydrophobic, and the dyes are more likely to aggregate and deposit on the adsorbent surface by electrostatic attraction, hydrogen bonding, and π-π accumulation. Therefore, this work provides a potential UiO-66/cotton fabric application for the effective adsorption of reactive dyes in textile wastewater.

Preparation of zeolitic imidazolate framework-67/wool fabric and its adsorption capacity for reactive dyes.

Zeolitic imidazolate framework-67 (ZIF-67) formed by Co2+ and 2-methylimidazole (MIM) is widely used for adsorption and separation of pollutants. However, there are some disadvantages for ZIF-67 powder, such as strong electrostatic interaction and difficulty in recovery from the liquid phase. The available way to solve the above problems is choosing a suitable substrate to load ZIF-67. The amino and hydroxyl of wool fabrics effectively capture and fix ZIF-67, making it easy to separate ZIF-67 by taking out the composite materials from aqueous solution. In this study, ZIF-67/Wool fabric (ZW) was successfully prepared. The results show that ZIF-67 has better adsorption performance for reactive dyes with more sulfonic groups, higher molecular weight and lower steric resistance. The equilibrium adsorption capacity of ZW for reactive red 195 was 4.15 mg g-1. The adsorption accorded with pseudo-second-order kinetic model and Langmuir isotherm. This study improved the application of ZIF-67, which provided a treatment method for dyeing wastewater and made it possible to recycle waste wool.