Integrating network pharmacology and experimental validation reveals therapeutic effects of D-mannose on NAFLD through mTOR suppression.

Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition and metabolic disorder, has emerged as a significant health issue worldwide. D-mannose, a natural monosaccharide widely existing in plants and animals, has demonstrated metabolic regulatory properties. However, the effect and mechanism by which D-mannose may counteract NAFLD have not been studied. In this study, network pharmacology followed by molecular docking analysis was utilized to identify potential targets of mannose against NAFLD, and the leptin receptor-deficient, genetically obese db/db mice was employed as an animal model of NAFLD to validate the regulation of D-mannose on core targets. As a result, 67 targets of mannose are predicted associated with NAFLD, which are surprisingly centered on the mechanistic target of rapamycin (mTOR). Further analyses suggest that mTOR signaling is functionally enriched in potential targets of mannose treating NAFLD, and that mannose putatively binds to mTOR as a core mechanism. Expectedly, repeated oral gavage of supraphysiological D-mannose ameliorates liver steatosis of db/db mice, which is based on suppression of hepatic mTOR signaling. Moreover, daily D-mannose administration reduced hepatic expression of lipogenic regulatory genes in counteracting NAFLD. Together, these findings reveal D-mannose as an effective and potential NAFLD therapeutic through mTOR suppression, which holds translational promise.

Novel players in organogenesis and flavonoid biosynthesis in cucumber glandular trichomes.

Glandular trichomes (GTs) are outgrowths of plant epidermal cells that secrete and store specialized secondary metabolites that protect plants against biotic and abiotic stresses and have economic importance for human use. While extensive work has been done to understand the molecular mechanisms of trichome organogenesis in Arabidopsis (Arabidopsis thaliana), which forms unicellular, nonglandular trichomes (NGTs), little is known about the mechanisms of GT development or regulation of secondary metabolites in plants with multicellular GTs. Here, we identified and functionally characterized genes associated with GT organogenesis and secondary metabolism in GTs of cucumber (Cucumis sativus). We developed a method for effective separation and isolation of cucumber GTs and NGTs. Transcriptomic and metabolomic analyses showed that flavonoid accumulation in cucumber GTs is positively associated with increased expression of related biosynthesis genes. We identified 67 GT development-related genes, the functions of 7 of which were validated by virus-induced gene silencing. We further validated the role of cucumber ECERIFERUM1 (CsCER1) in GT organogenesis by overexpression and RNA interference transgenic approaches. We further show that the transcription factor TINY BRANCHED HAIR (CsTBH) serves as a central regulator of flavonoid biosynthesis in cucumber GTs. Work from this study provides insight into the development of secondary metabolite biosynthesis in multicellular GTs.

Single-cell N6-methyladenosine-related genes function within the tumor microenvironment to affect the prognosis and treatment sensitivity in patients with gastric cancer.

BACKGROUND: Gastric cancer (GC) ranks fifth for morbidity and third for mortality worldwide. The N6-methyladenosine (m6A) mRNA methylation is crucial in cancer biology and progression. However, the relationship between m6A methylation and gastric tumor microenvironment (TME) remains to be elucidated. METHODS: We combined single-cell and bulk transcriptome analyses to explore the roles of m6A-related genes (MRG) in gastric TME. RESULTS: Nine TME cell subtypes were identified from 23 samples. Fibroblasts were further grouped into four subclusters according to different cell markers. M6A-mediated fibroblasts may guide extensive intracellular communications in the gastric TME. The m6A-related genes score (MRGs) was output based on six differentially expressed single-cell m6A-related genes (SCMRDEGs), including GHRL, COL4A1, CAV1, GJA1, TIMP1, and IGFBP3. The protein expression level was assessed by immunohistochemistry. We identified the prognostic value of MRGs and constructed a nomogram model to predict GC patients' overall survival. MRGs may affect treatment sensitivity in GC patients. CONCLUSION: Our study visualized the cellular heterogeneity of TME at the single-cell level, revealed the association between m6A mRNA modification and intracellular communication, clarified MRGs as an independent risk factor of prognosis, and provided a reference for follow-up treatment.

2D materials-based photodetectors combined with ferroelectrics.

Photodetectors are essential optoelectronic devices that play a critical role in modern technology by converting optical signals into electrical signals, which are one of the most important sensors of the informational devices in current 'Internet of Things' era. Two-dimensional (2D) material-based photodetectors have excellent performance, simple design and effortless fabrication processes, as well as enormous potential for fabricating highly integrated and efficient optoelectronic devices, which has attracted extensive research attention in recent years. The introduction of spontaneous polarization ferroelectric materials further enhances the performance of 2D photodetectors, moreover, companying with the reduction of power consumption. This article reviews the recent advances of materials, devices in ferroelectric-modulated photodetectors. This review starts with the introduce of the basic terms and concepts of the photodetector and various ferroelectric materials applied in 2D photodetectors, then presents a variety of typical device structures, fundamental mechanisms and potential applications under ferroelectric polarization modulation. Finally, we summarize the leading challenges currently confronting ferroelectric-modulated photodetectors and outline their future perspectives.

Application of 3D computed tomography in emphysematous parenchyma patients scheduled for bronchoscopic lung volume reduction.

Bronchoscopic lung volume reduction (BLVR) is a feasible, safe, effective and minimally invasive technique to significantly improve the quality of life of advanced severe chronic obstructive pulmonary disease (COPD). In this study, three-dimensional computed tomography (3D-CT) automatic analysis software combined with pulmonary function test (PFT) was used to retrospectively evaluate the postoperative efficacy of BLVR patients. The purpose is to evaluate the improvement of lung function of local lung tissue after operation, maximize the benefits of patients, and facilitate BLVR in the treatment of patients with advanced COPD. All the reported cases of advanced COPD patients treated with BLVR with one-way valve were collected and analysed from 2017 to 2020. Three-dimensional-CT image analysis software system was used to analyse the distribution of low-density areas <950 Hounsfield units in both lungs pre- and post- BLVR. Meanwhile, all patients performed standard PFT pre- and post-operation for retrospective analysis. We reported six patients that underwent unilateral BLVR with 1 to 3 valves according to the range of emphysema. All patients showed a median increase in forced expiratory volume in 1 second (FEV1) of 34%, compared with baseline values. Hyperinflation was reduced by 16.6% (range, 4.9%-47.2%). The volumetric measurements showed a significant reduction in the treated lobe volume among these patients. Meanwhile, the targeted lobe volume changes were inversely correlated with change in FEV1/FEV1% in patients with heterogeneous emphysematous. We confirm that 3D-CT analysis can quantify the changes of lung volume, ventilation and perfusion, to accurately evaluate the distribution and improvement of emphysema and rely less on the observer.

A multi-omics analysis reveals CLSPN is associated with prognosis, immune microenvironment and drug resistance in cancers.

BACKGROUND: Immunotherapy is effective only in limited patients. It is urgent to discover a novel biomarker to predict immune cells infiltration status and immunotherapy response of different cancers. CLSPN has been reported to play a pivotal role in various biological processes. However, a comprehensive analysis of CLSPN in cancers has not been conducted. METHODS: To show the whole picture of CLSPN in cancers, a pan-cancer analysis was conducted in 9125 tumor samples across 33 cancer types by integrating transcriptomic, epigenomic and pharmacogenomics data. Moreover, the role of CLSPN in cancer was validated by CCK-8, EDU, colony formation and flow cytometry in vitro and tumor cell derived xenograft model in vivo. RESULTS: CLSPN expression was generally upregulated in most cancer types and was significantly associated with prognosis in different tumor samples. Moreover, elevated CLSPN expression was closely correlated with immune cells infiltration, TMB (tumor mutational burden), MSI (microsatellite instability), MMR (mismatch repair), DNA methylation and stemness score across 33 cancer types. Enrichment analysis of functional genes revealed that CLSPN participated in the regulation of numerous signaling pathways involved in cell cycle and inflammatory response. The expression of CLSPN in LUAD patients were further analyzed at the single-cell level. Knockdown CLSPN significantly inhibited cancer cell proliferation and cell cycle related cyclin-dependent kinase (CDK) family and Cyclin family expression in LUAD (lung adenocarcinoma) both in vitro and in vivo experiments. Finally, we conducted structure-based virtual screening by modelling the structure of CHK1 kinase domain and Claspin phosphopeptide complex. The top five hit compounds were screened and validated by molecular docking and Connectivity Map (CMap) analysis. CONCLUSION: Our multi-omics analysis offers a systematic understanding of the roles of CLSPN in pan-cancer and provides a potential target for future cancer treatment.

Animal host range of mpox virus.

Mpox is caused by the mpox virus, which belongs to the Orthopoxvirus genus and Poxviridae family. Animal hosts, such as African rodents, mice, prairie dogs, and non-human primates, play important roles in the development and transmission of outbreaks. Laboratory animal infection experiments have demonstrated that some animals are susceptible to mpox virus. This review summarizes the current progress on the animal hosts for mpox virus. The surveillance of mpox virus in animal hosts will provide important insights into virus tracing, analysis of mutation evolutionary patterns, transmission mechanisms, and development of control measures.

Wafer-scale inverted gallium phosphide-on-insulator rib waveguides for nonlinear photonics.

We report a gallium phosphide-on-insulator (GaP-OI) photonic platform fabricated by an intermediate-layer bonding process aiming to increase the manufacture scalability in a low-cost manner. This is enabled by the "etch-n-transfer" sequence, which results in inverted rib waveguide structures. The shallow-etched 1.8 µm-wide waveguide has a propagation loss of 23.5 dB/cm at 1550 nm wavelength. Supercontinuum generation based on the self-phase modulation effect is observed when the waveguides are pumped by femtosecond pulses. The nonlinear refractive index of GaP, n2, is extracted to be 1.9 × 10-17 m2/W, demonstrating the great promise of the GaP-OI platform in third-order nonlinear applications.

Molecular Insights into Bifunctional Ambruticin DH3 for Substrate Specificity and Catalytic Mechanism.

Dehydratase (DH), a domain located at polyketide synthase (PKS) modules, commonly catalyzes the dehydration of ß-hydroxy to an α,ß-unsaturated acyl intermediate. As a unique bifunctional dehydratase, AmbDH3 (the DH domain of module 3 of the ambruticin PKS) is verified to be responsible for both dehydration and the following pyran-forming cyclization. Besides, in vitro studies showed that its catalytic efficiency varies with different chiral substrates. However, the detailed molecular mechanism of AmbDH3 remains unclear. In this work, the structural rationale for the substrate specificity (2R/2S- and 6R/6S-substrates) in AmbDH3 was elucidated and the complete reaction pathways including dehydration and cyclization were presented. Both MD simulations and binding free energy calculations indicated AmbDH3 had a stronger preference for 2R-substrates (2R6R-2, 2R6S-3) than 2S-substrates (2S6R-1), and residue H51 and G61 around the catalytic pocket were emphasized by forming stable hydrogen bonds with 2R-substrates. In addition, AmbDH3's mild tolerance at C6 was explained by comparison of substrate conformation and hydrogen bond network in 6S- and 6R-substrate systems. The QM/MM results supported a consecutive one-base dehydration and cyclization mechanism for 2R6S-3 substrate with the energy barrier of 25.2 kcal mol-1 and 24.5 kcal mol-1 , respectively. Our computational results uncover the substrate recognition and catalytic process of the first bifunctional dehydratase-cyclase AmbDH3, which will shed light on the application of multifunctional DH domains in PKSs for diverse natural product analogs and benefit the chemoenzymatic synthesis of stereoselective pyran-containing products.

Development of a counterselectable system for rapid and efficient CRISPR-based genome engineering in Zymomonas mobilis.

BACKGROUND: Zymomonas mobilis is an important industrial bacterium ideal for biorefinery and synthetic biology studies. High-throughput CRISPR-based genome editing technologies have been developed to enable targeted engineering of genes and hence metabolic pathways in the model ZM4 strain, expediting the exploitation of this biofuel-producing strain as a cell factory for sustainable chemicals, proteins and biofuels production. As these technologies mainly take plasmid-based strategies, their applications would be impeded due to the fact that curing of the extremely stable plasmids is laborious and inefficient. Whilst counterselection markers have been proven to be efficient for plasmid curing, hitherto only very few counterselection markers have been available for Z. mobilis. RESULTS: We constructed a conditional lethal mutant of the pheS gene of Z. mobilis ZM4, clmPheS, containing T263A and A318G substitutions and coding for a mutated alpha-subunit of phenylalanyl-tRNA synthetase to allow for the incorporation of a toxic analog of phenylalanine, p-chloro-phenylalanine (4-CP), into proteins, and hence leading to inhibition of cell growth. We demonstrated that expression of clmPheS driven by a strong Pgap promoter from a plasmid could render the Z. mobilis ZM4 cells sufficient sensitivity to 4-CP. The clmPheS-expressing cells were assayed to be extremely sensitive to 0.2 mM 4-CP. Subsequently, the clmPheS-assisted counterselection endowed fast curing of genome engineering plasmids immediately after obtaining the desired mutants, shortening the time of every two rounds of multiplex chromosome editing by at least 9 days, and enabled the development of a strategy for scarless modification of the native Z. mobilis ZM4 plasmids. CONCLUSIONS: This study developed a strategy, coupling an endogenous CRISPR-based genome editing toolkit with a counterselection marker created here, for rapid and efficient multi-round multiplex editing of the chromosome, as well as scarless modification of the native plasmids, providing an improved genome engineering toolkit for Z. mobilis and an important reference to develope similar genetic manipulation systems in other non-model organisms.

Correlation Between the Peripheral Neuropathy and Levels of hs-CRP, IL-1ß and IL-6 in Senile Parkinson's Disease Patients.

This study was carried out to investigate the correlation between the onset of peripheral neuropathy and levels of hypersensitive C-reactive protein (hs-CRP), interleukin 1ß (IL-1ß) and IL-6 in senile Parkinson's disease (PD) patients. For this purpose, a total of 60 PD patients and 60 age-matched healthy subjects were enrolled in this study and received the assessment for peripheral nerves by using the quantified method. Besides, levels of hs-CRP, IL-1ß and IL-6 in serum were determined to analyze the correlation between the clinical features, including the severity of PD and cognitive decline, and the levels of hs-CRP, IL-1ß and IL-6. Results showed that PD patients had more cases of peripheral neuropathy than those in the healthy control group. Levels of hs-CRP, IL-1ß and IL-6 in the serum of PD patients were much higher than those in the healthy control (P<0.05). Besides, PD patients had lower scores of MMSE and MoCA but higher CNPI scores when compared to the healthy control group. As a result, we found that the severity of peripheral neuropathy was in a positive correlation with the levels of hs-CRP, IL-1ß and IL-6. It was concluded that PD patients generally have peripheral neuropathy that may correlate with the increases in the levels of hs-CRP, IL-1ß and IL-6, and early intervention may mitigate the development and progression of peripheral neuropathy.

Exploring biomarkers associated with severity of knee osteoarthritis in Southern China using widely targeted metabolomics.

BACKGROUND: Metabolomics is a tool to study the pathogenesis of diseases and their associated metabolites, but there are still insufficient metabolomic studies on severe knee osteoarthritis.To investigate the differences in serum metabolites between healthy populations and knee osteoarthritis (KOA) patients in Southern China using widely targeted metabolomics, and to explore biomarkers and their metabolic pathways that could be associated with the severity of KOA. METHODS: There were 10 healthy individuals in the control group and 32 patients with KOA. According to the Kellgren-Lawrence (KL) grading system, KOA was further divided into mild (n = 13, KL grade 1 and 2) and severe (n = 19, KL grade 3 and 4). Serum samples from all participants were collected and analyzed metabolomics based on ultra-performance liquid chromatography/electrospray ionization/tandem mass spectrometry. We screened for differential metabolites between patients and controls, and between mild and severe KOA. We explored the metabolic pathways involved in differential metabolism using the Kyoto Encyclopedia of Genes and Genomes database. RESULTS: Sixty-one metabolites were differentially expressed in the sera of the patient group compared with the control group (45 upregulated and 16 downregulated). Analysis of the mild and severe KOA groups showed a total of 12 differential metabolites. Receiver operating characteristic curve analysis showed N-alpha-acetyl-L-asparagine was a good predictor of advanced osteoarthritis(OA).Differential metabolites are enriched in multiple pathways such as arachidonic acid metabolism. CONCLUSION: Widely targeted metabolomics found that upregulation of the amino acid metabolite N-α-acetyl-L-asparagine was significantly associated with severe KOA and could be a biomarker for predicting severity of KOA. Arachidonic acid metabolism may play an important role in patients with severe KOA.

Identification and Functional Characterization of CsMYCs in Cucumber Glandular Trichome Development.

Glandular trichomes (GTs), specialized structures formed by the differentiation of plant epidermal cells, are known to play important roles in the resistance of plants to external biotic and abiotic stresses. These structures are capable of storing and secreting secondary metabolites, which often have important agricultural and medicinal values. In order to better understand the molecular developmental mechanisms of GTs, studies have been conducted in a variety of crops, including tomato (Solanum lycopersicum), sweetworm (Artemisia annua), and cotton (Gossypium hirsutum). The MYC transcription factor of the basic helix-loop-helix (bHLH) transcription factor family has been found to play an important role in GT development. In this study, a total of 13 cucumber MYC transcription factors were identified in the cucumber (Cucumis sativus L.) genome. After performing phylogenetic analyses and conserved motifs on the 13 CsMYCs in comparison to previously reported MYC transcription factors that regulate trichome development, seven candidate MYC transcription factors were selected. Through virus-induced gene silencing (VIGS), CsMYC2 is found to negatively regulate GT formation while CsMYC4, CsMYC5, CsMYC6, CsMYC7, and CsMYC8 are found to positively regulate GT formation. Furthermore, the two master effector genes, CsMYC2 and CsMYC7, are observed to have similar expression patterns indicating that they co-regulate the balance of GT development in an antagonistic way.

The Motion Paradigm of Pre-Dock Zearalenone Hydrolase Predictions with Molecular Dynamics and the Docking Phase with Umbrella Sampling.

Zearalenone (ZEN) is one of the most prevalent estrogenic mycotoxins, is produced mainly by the Fusarium family of fungi, and poses a risk to the health of animals. Zearalenone hydrolase (ZHD) is an important enzyme capable of degrading ZEN into a non-toxic compound. Although previous research has investigated the catalytic mechanism of ZHD, information on its dynamic interaction with ZEN remains unknown. This study aimed to develop a pipeline for identifying the allosteric pathway of ZHD. Using an identity analysis, we identified hub genes whose sequences can generalize a set of sequences in a protein family. We then utilized a neural relational inference (NRI) model to identify the allosteric pathway of the protein throughout the entire molecular dynamics simulation. The production run lasted 1 microsecond, and we analyzed residues 139-222 for the allosteric pathway using the NRI model. We found that the cap domain of the protein opened up during catalysis, resembling a hemostatic tape. We used umbrella sampling to simulate the dynamic docking phase of the ligand-protein complex and found that the protein took on a square sandwich shape. Our energy analysis, using both molecular mechanics/Poisson-Boltzmann (Generalized-Born) surface area (MMPBSA) and Potential Mean Force (PMF) analysis, showed discrepancies, with scores of -8.45 kcal/mol and -1.95 kcal/mol, respectively. MMPBSA, however, obtained a similar score to that of a previous report.

Potentially suitable distribution areas of Populus euphratica and Tamarix chinensis by MaxEnt and random forest model in the lower reaches of the Heihe River, China.

Populus euphratica and Tamarix chinensis play a vital role in windbreak and sand fixation, maintaining species diversity and ensuring community stability. Managing and protecting the P. euphratica and T. chinensis forests in the Heihe River's lower reaches is an urgent issue to maintain the desert region's ecological balance. In this study, based on the distribution points of P. euphratica and T. chinensis species and environmental data, MaxEnt and random forest (RF) models were used to characterize the potential distribution areas of P. euphratica and T. chinensis in the lower reaches of the Heihe River. The results showed that the accuracy of the RF model was much higher than that of the MaxEnt model. Both the RF and MaxEnt models showed that the distance to the river greatly influenced the distribution of P. euphratica and T. chinensis. Furthermore, the RF model predicted significantly larger highly suitable areas for both P. euphratica and T. chinensis than the MaxEnt model. Our study enhances the understanding of the species' spatial distribution, offering valuable insights for practical management and conservation strategies.

Does losing money truly hurt? The shared neural bases of monetary loss and pain.

Both monetary loss and pain have been studied for decades, but evidence supporting the relationship between them is still lacking. We conducted a meta-analysis to explore the overlapping brain regions between monetary loss and pain, including physical pain and social pain. Regardless of the type of pain experienced, activation of the anterior insula was a shared neural representation of monetary loss and pain. The network representation pattern of monetary loss was more similar to that of social pain than that of physical pain. In conclusion, our research provided evidence of the common neural correlates of monetary loss and pain.

Palmitoylation of SARS-CoV-2 S protein is critical for S-mediated syncytia formation and virus entry.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The S protein is the key viral protein for associating with ACE2, the receptor for SARS-CoV-2. There are many kinds of posttranslational modifications in S protein. However, the detailed mechanism of palmitoylation of SARS-CoV-2 S remains to be elucidated. In our current study, we characterized the palmitoylation of SARS-CoV-2 S. Both the C15 and cytoplasmic tail of SARS-CoV-2 S were palmitoylated. Fatty acid synthase inhibitor C75 and zinc finger DHHC domain-containing palmitoyltransferase (ZDHHC) inhibitor 2-BP reduced the palmitoylation of S. Interestingly, palmitoylation of SARS-CoV-2 S was not required for plasma membrane targeting of S but was critical for S-mediated syncytia formation and SARS-CoV-2 pseudovirus particle entry. Overexpression of ZDHHC2, ZDHHC3, ZDHHC4, ZDHHC5, ZDHHC8, ZDHHC9, ZDHHC11, ZDHHC14, ZDHHC16, ZDHHC19, and ZDHHC20 promoted the palmitoylation of S. Furthermore, those ZDHHCs were identified to associate with SARS-CoV-2 S. Our study not only reveals the mechanism of S palmitoylation but also will shed important light into the role of S palmitoylation in syncytia formation and virus entry.

Hydrophilic Nanocomposite Films with a Fence-Structure-Induced Labyrinth Effect for Greenhouse Cooling and Light Enhancement.

In this paper, we reported a new kind of cooling and light-enhanced hydrophilic nanocomposite film (PE/JW-0.8%) with low-density polyethylene (LDPE) as the substrate. The wetting, photophysical, and mechanical properties of PE/JW-0.8% were tested. The emission band of the fluorescence centers at 420 nm, which is perfectly consistent with the absorption spectrum of plant photosynthesis. In addition, light can be scattered by PE/JW-0.8% to achieve a larger light distribution area. PE/JW-0.8% showed a good durability of hydrophilicity in the water rinsing test. Meanwhile, the elongation at the break of the film was significantly increased. Benefiting from the fence structure induced labyrinth effect, a maximum reduction of 6.7 °C in temperature monitoring for PE/JW-0.8% was observed in the detailed field experiments. Light intensity monitoring showed that light intensity in PE/JW-0.8% increased by a maximum of 57.1% compared to PE/LH. In the biological quality analysis of melon, it was found that the soluble sugar, soluble solid, and vitamin C content of melon increased by 13.34, 22.96, and 50.95%, respectively. In conclusion, these results confirm that PE/JW-0.8% has great application potential in the field of facility agriculture, buildings, and photovoltaic modules.

Comprehensive estimation for the length and dispersion of COVID-19 incubation period: a systematic review and meta-analysis.

PURPOSE: To estimate the central tendency and dispersion for incubation period of COVID-19 and, in turn, assess the effect of a certain length of quarantine for close contacts in active monitoring. METHODS: Literature related to SARS-CoV-2 and COVID-19 was searched through April 26, 2020. Quality was assessed according to Agency for Healthcare Research and Quality guidelines. Log-normal distribution for the incubation period was assumed to estimate the parameters for each study. Incubation period median and dispersion were estimated, and distribution was simulated. RESULTS: Fifty-six studies encompassing 4095 cases were included in this meta-analysis. The estimated median incubation period for general transmissions was 5.8 days [95% confidence interval (95% CI): 5.3, 6.2]. Incubation period was significantly longer for asymptomatic transmissions (median: 7.7 days; 95% CI 6.3, 9.4) than for general transmissions (P = 0.0408). Median and dispersion were higher for SARS-CoV-2 incubation compared to other viral respiratory infections. Furthermore, about 12 in 10,000 contacts in active monitoring would develop symptoms after 14 days, or below 1 in 10,000 for asymptomatic transmissions. Meta-regression suggested that each 10-year increase in age resulted in an average 16% increment in length of median incubation (incubation period ratio, 1.16, 95% CI 1.01, 1.32; P = 0.0250). CONCLUSION: This study estimated the median and dispersion of the SARS-CoV-2 incubation period more precisely. A 14-day quarantine period is sufficient to trace and identify symptomatic infections.

Iron-catalyzed regioselective synthesis of (E)-vinyl sulfones mediated by unprotected hydroxylamines.

An Fe-catalyzed unprotected hydroxylamine mediated Heck-type coupling between sulfinic acids and alkenes for the regioselective synthesis of (E)-vinyl sulfones has been developed. Mechanism studies indicated for the first time that a radical process may be involved and that hydroxylamines play multiple roles, including those of a mild oxidant and an in situ base. It was found for the first time that this transformation not only realizes C-S bond construction promoted by unprotected hydroxylamines, but also provides a practical and complementary method for the preparation of structurally important (E)-vinyl sulfones.