Fluorination effects on non-covalent binding forces: A rotational study on the 2-(trifluoromethyl)acrylic acid-water complex.

This study explores the effects of the -CF3 group on non-covalent interactions through a comprehensive rotational investigation of the 2-(trifluoromethyl)acrylic acid-water complex. Employing Fourier transform microwave spectroscopy complemented by quantum chemical calculations, two isomers, i.e., s-cis and s-trans structures, have been observed in the pulsed jet. Based on relative intensity measurements, the s-cis to the s-trans population ratio was experimentally estimated to be âˆ¼ 1:1.2. Subsequently, a comparison of the non-covalent interactions was carried out between the three similar complexes, acrylic acid-water, methacrylic acid-water, and 2-(trifluoromethyl)acrylic acid-water, offering quantitative insights into fluorination affecting the strength of the formed hydrogen bonds important, e.g., in molecular recognition.

Elucidating the structural and conformational preferences of bioactive chromone and its monohydrate through advanced rotational spectroscopy.

Chromones are a class of naturally occurring compounds, renowned for their diverse biological activities with significant relevance in medicine and biochemistry. This study marks the first analysis of rotational spectra of both the chromone monomer and its monohydrate through Fourier transform microwave spectroscopy. The observation of nine mono-substituted 13C isotopologues facilitated a semi-experimental determination of the equilibrium structure of the chromone monomer. In the case of chromone monohydrate, two distinct isomers were identified, each characterized by a combination of O-H⋯O and C-H⋯O hydrogen bonds involving the chromone's carbonyl group. This study further delved into intermolecular non-covalent interactions, employing different theoretical approaches. The relative population ratio of the two identified isomers was estimated to be about 2:1 within the supersonic jet.

C···S Tetrel Bond Favored in the Phenyl Isothiocyanate-CO2 Complex: A Rotational Study.

The rotational spectrum of the phenyl isothiocyanate-CO2 complex was investigated by pulsed-jet Fourier transform microwave spectroscopy complemented by quantum chemical calculations. Only one isomer, with CO2 almost in the plane of phenyl isothiocyanate, has been detected in the pulsed jet, of which the spectrum displays a quadrupole coupling hyperfine structure due to the presence of a 14N nucleus (I = 1). This structure is nearly equal to the lowest energy geometry obtained by B3LYP-D3(BJ)/6-311++G(d,p), which has been dominated by a C···S tetrel bond (n → π* interaction) and one secondary C-H···O hydrogen bond (n → σ* interaction). Molecular electrostatic potential and natural bond orbital analysis were used to characterize the noncovalent interactions of the complex. The results from this study would lay the groundwork for the design and advancement of materials that exhibit high efficiency in capturing CO2.

L-glutamine protects against enterohemorrhagic Escherichia coli infection by inhibiting bacterial virulence and enhancing host defense concurrently.

IMPORTANCE: The type 3 secretion system (T3SS) was obtained in many Gram-negative bacterial pathogens, and it is crucial for their pathogenesis. Environmental signals were found to be involved in the expression regulation of T3SS, which was vital for successful bacterial infection in the host. Here, we discovered that L-glutamine (Gln), the most abundant amino acid in the human body, could repress enterohemorrhagic Escherichia coli (EHEC) T3SS expression via nitrogen metabolism and therefore had potential as an antivirulence agent. Our in vitro and in vivo evidence demonstrated that Gln could decline EHEC infection by attenuating bacterial virulence and enhancing host defense simultaneously. We repurpose Gln as a potential treatment for EHEC infection accordingly.

Conformational equilibria and interaction preference in the complex of isoprene-maleic anhydride.

The rotational spectrum of the isoprene-maleic anhydride complex has been investigated by pulsed jet Fourier transform microwave spectroscopy and interpreted with complementary quantum chemical calculations. Theoretical predictions have yielded four plausible isomers, all residing within an energy window of 12 kJ mol-1. However, two distinct isomers characterized by a π-π stacked configuration have been experimentally observed in pulsed jets, which have differed in the orientation of isoprene over maleic anhydride. The relative population ratio of the two detected isomers has been estimated to be NI/NII ≈ 3/1 from rigorous measurements of the relative intensity on a set of µc-type transitions. Remarkably, this study underscores the pivotal role played by the interaction between the CC bonding orbital (π) of isoprene and the CC antibonding orbital (π*) of maleic anhydride in stabilizing the target complex.

Fluorination effects probed in 4-fluoroacetophenone and its monohydrate.

Rotational spectra of the 4-fluoroacetophenone monomer and its monohydrate were investigated by Fourier transform microwave spectroscopy complemented with quantum chemical calculations. One conformer of 4-fluoroacetophenone and two isomers of 4-fluoroacetophenone-H2O have been observed in the pulsed jets. The observation of all mono-substituted 13C isotopologues in natural abundance allows an accurate structural determination of the 4-fluoroacetophenone monomer. Both detected isomers of 4-fluoroacetophenone-H2O are stabilized by a dominant O-H⋯O and a secondary C-H⋯O hydrogen bond. The fluorination effects on the geometries, intermolecular non-covalent interactions and V3 barrier of the methyl internal rotation were analysed. The relative population ratio of the two observed isomers for 4-fluoroacetophenone-H2O was also estimated to be NI/NII ≈ 7/1.

Gallic acid improves the metformin effects on diabetic kidney disease in mice.

OBJECTIVES: Metformin is an antidiabetic agent that is used as the first-line treatment of type 2 diabetes mellitus. Gallic acid is a type of phenolic acid that has been shown to be a potential drug candidate to treat diabetic kidney disease, an important complication of diabetes. We aimed to test whether a combination of gallic acid and metformin can exert synergetic effect on diabetic kidney disease in diabetic mice model. METHODS: Streptozotocin (65 mg/kg) intraperitoneal injection was used to induce diabetic kidney disease in mice. The diabetic mice were treated with saline (Vehicle), gallic acid (GA) (30 mg/kg), metformin (MET) (200 mg/kg), or the combination of gallic acid (30 mg/kg) and metformin (200 mg/kg) (GA + MET). RESULTS: Our results demonstrated that compared to the untreated diabetic mice, all three strategies (GA, MET, and GA + MET) exhibited various effects on improving renal morphology and functions, reducing oxidative stress in kidney tissues, and restoring AMP-activated protein kinase (AMPK)/silent mating type information regulation 2 homolog 1 (SIRT1) signaling in kidney tissues of diabetic mice. Notably, the combination strategy (GA + MET) provided the most potent renal protection effects than any single strategies (GA or MET). CONCLUSION: Our results support the hypothesis that gallic acid might serve as a potential supplement to metformin to enhance the therapeutical effect of metformin.

Laboratory Rotational Spectrum and Radio-Astronomical Search of Acetoin.

The rotational spectrum of acetoin (3-hydroxy-2-butanone) was measured by using Fourier transform microwave spectroscopy with the aid of quantum chemical calculations. Only one conformer of acetoin was detected in the pulsed jet, whose spectrum featured the splittings raised from the internal rotation of the methyl top linking to the C═O group. Based on the spectroscopic result, radio-astronomical searches for acetoin were carried out toward the massive star-forming region Sgr B2(N) using the Shanghai Tianma 65 m and IRAM 30 m radio telescopes. No lines belonging to acetoin were detected toward Sgr B2(N). Its upper limit of column density was calculated.

Comparative Evaluation of Standard RT-PCR Assays and Commercial Real-Time RT-PCR Kits for Detection of Lassa Virus.

Lassa virus (LASV) is a causative agent of hemorrhagic fever epidemic in West Africa. In recent years, it has been transmitted several times to North America, Europe, and Asia. Standard reverse transcription (RT)-PCR and real-time RT-PCR are extensively used for early detection of LASV. However, the high nucleotide diversity of LASV strains complicates the development of appropriate diagnostic assays. Here, we analyzed LASV diversity clustered with geographic location and evaluated the specificity and sensitivity of two standard RT-PCR methods (GPC RT-PCR/1994 and 2007) and four commercial real-time RT-PCR kits (namely, Da an, Mabsky, Bioperfectus, and ZJ) to detect six representative LASV lineages using in vitro synthesized RNA templates. The results showed that the GPC RT-PCR/2007 assay had better sensitivity compared to the GPC RT-PCR/1994 assay. The Mabsky and ZJ kits were able to detect all RNA templates of six LASV lineages. Contrastingly, the Bioperfectus and Da an kits failed to detect lineages IV and V/VI. The limit of detection for lineage I with the Da an, Bioperfectus, and ZJ kits were significantly higher than that of the Mabsky kit at an RNA concentration of 1 × 1010 to 1 × 1011 copies/mL. The Bioperfectus and Da an kits detected lineages II and III at an RNA concentration of 1 × 109 copies/mL, higher than that of the other kits. In conclusion, the GPC RT-PCR/2007 assay and the Mabsky kit were suitable assays for the detection of LASV strains based on good analytical sensitivity and specificity. IMPORTANCE Lassa virus (LASV) is a significant human pathogen causing hemorrhagic fever in West Africa. Increased traveling around the world raises the risk of imported cases to other countries. The high nucleotide diversity of LASV strains clustered with geographic location complicates the development of appropriate diagnostic assays. In this study, we showed that the GPC reverse transcription (RT)-PCR/2007 assay and the Mabsky kit are suitable for detecting most LASV strains. Future assays for molecular detection of LASV should be based on specific countries/regions along with new variants.

Stepwise hydrations of anhydride tuned by hydrogen bonds: rotational study on maleic anhydride-(H2O)1-3.

The rotational spectra of maleic anhydride-(H2O)1-3 have been investigated for the first time by using pulsed jet Fourier transform microwave spectroscopy with complementary computational analyses. The experimental evidence points out that water tends to self-aggregate with hydrogen bonds and form homodromic cycles. Differences in bond lengths and charge distribution between the two carbonyl sites have been observed upon stepwise hydrations, which might further introduce a selectivity on the nucleophilic attack sites of hydrolysis. This study provides an important insight into the incipient solvation process (microsolvation) of maleic anhydride in water by understanding the cooperation and rearrangement of intermolecular hydrogen bonds in its stepwise hydrates.

Insights into the Diels-Alder Reaction of Furan with Maleic Anhydride from Its Prereactive Intermediate.

The prereactive intermediate in the furan-maleic anhydride cycloaddition, a classical Diels-Alder reaction, has been captured and characterized in pulsed jets by Fourier transform microwave spectroscopy for the first time. The observed species is stabilized by the π-π* interaction between the two moieties, which connects to the endo channel of the cycloaddition. The secondary interactions between the C=C and C=O in the observed isomer are accountable for its lower energy with respect to the one with the exo channel. The present study tries to fill the significant void of the experimental information on prereactive intermediates as the first stage of Diels-Alder cycloadditions, by outlining the stability of the prereactive intermediate and its accurate molecular structure and by emphasizing the role of the π-π* interaction in governing the stereochemical outcome of the reaction.

Accurate Geometry and Non-Covalent Interactions in 1-Phenylethanol and its Monohydrate: A Rotational Study.

The pure rotational spectra of 1-phenylethanol and its monohydrate were measured by using a pulsed jet Fourier transform microwave spectrometer. One conformer of the 1-phenylethanol monomer with the trans form was observed in the pulsed jet. The experimental values of rotational constants of ten isotopologues, including eight mono-substituted 13 C and one D isotopologues, allow an accurate structure determination of the skeleton of 1-phenylethanol. For its monohydrate, only one isomer has been observed, of which 1-phenylethanol adopts the trans form and binds with water through an O-H⋅⋅⋅Ow and an Ow -H⋅⋅⋅π hydrogen bond. Each rotational transition displays a doublet with a relative intensity ratio of 1 : 3, due to a hindered internal rotation of water around its C2 axis. This study provides the information on accurate geometry of 1-phenylethanol (PE) and large amplitude motion of water in the PE monohydrate.

Rolling mill health states diagnosing method based on multi-sensor information fusion and improved DBNs under limited datasets.

Due to the harsh working conditions and high cost of data acquisition in the actual environment of modern rolling mills, the resulting limited datasets issue leading in performance collapse of traditional deep learning (DL) methods has been plaguing researchers and needs to be urgently addressed. Hence, an improved single-sensor Deep Belief Network (IDBN) is first proposed to repetitively extract valuable information from hidden features and visible features of the previous improved Restricted Boltzmann Machine (IRBM) to alleviate this issue. Next, the multi-sensor IDBNs (MSIDBNs) are applied to obtain complementary and enriched health state features from different multi-sensor data to cope with limited datasets more effectively. Then, the Fast Fourier Transform (FFT) technique is adopted for the multi-sensor information to further enhance the effectiveness of feature extraction. Most importantly, the redefined pretraining and finetuning stages are designed for the MSIDBNs. Meanwhile, the optimal placement of multiple sensors is fully discussed to obtain the most efficient information about health content. Finally, two limited datasets are conducted to validate the superiority of the proposed MSIDBNs. Results show that the proposed MSIDBNs are capable of extracting valuable features from multi-sensor information and achieving more remarkable performance compared with the state-of-the-art (SOTA) methods under limited datasets.

Rapid identification of salmonella serovars by using Raman spectroscopy and machine learning algorithm.

A widespread and escalating public health problem worldwide is foodborne illness, and foodborne Salmonella infection is one of the most common causes of human illness.For the three most pathogenic Salmonella serotypes, Raman spectroscopy was employed to acquire spectral data.As machine learning offers high efficiency and accuracy, we have chosen the convolutional neural network(CNN), which is suitable for solving multi-classification problems, to do in-depth mining and analysis of Raman spectral data.To optimize the instrument parameters, we compared three laser wavelengths: 532, 638, and 785 nm.Ultimately, the 532 nm wavelength was chosen as the most effective for detecting Salmonella.A pre-processing step is necessary to remove interference from the background noise of the Raman spectrum.Our study compared the effects of five spectral preprocessing methods, Savitzky-Golay smoothing (SG), Multivariate Scatter Correction (MSC), Standard Normal Variate (SNV), and Hilbert Transform (HT), on the predictive power of CNN models.Accuracy(ACC), Precision, Recall, and F1-score 4 machine learning evaluation indicators are used to evaluate the model performance under different preprocessing methods.In the results, SG combined with SNV was found to be the most accurate spectral pre-processing method for predicting Salmonella serotypes using Raman spectroscopy, achieving an accuracy of 98.7% for the training set and over 98.5% for the test set in CNN model.Pre-processing spectral data using this method yields higher accuracy than other methods.As a conclusion, the results of this study demonstrate that Raman spectroscopy when used in conjunction with a convolutional neural network model enables the rapid identification of three Salmonella serotypes at the single-cell level, and that the model has a great deal of potential for distinguishing between different serotypes of pathogenic bacteria and closely related bacterial species.This is vital to preventing outbreaks of foodborne illness and the spread of foodborne pathogens.

Identification of foodborne pathogenic bacteria using confocal Raman microspectroscopy and chemometrics.

Rapid and accurate identification of foodborne pathogenic bacteria is of great importance because they are often responsible for the majority of serious foodborne illnesses. The confocal Raman microspectroscopy (CRM) is a fast and easy-to-use method known for its effectiveness in detecting and identifying microorganisms. This study demonstrates that CRM combined with chemometrics can serve as a rapid, reliable, and efficient method for the detection and identification of foodborne pathogenic bacteria without any laborious pre-treatments. Six important foodborne pathogenic bacteria including S. flexneri, L. monocytogenes, V. cholerae, S. aureus, S. typhimurium, and C. botulinum were investigated with CRM. These pathogenic bacteria can be differentiated based on several characteristic peaks and peak intensity ratio. Principal component analysis (PCA) was used for investigating the difference of various samples and reducing the dimensionality of the dataset. Performances of some classical classifiers were compared for bacterial detection and identification including decision tree (DT), artificial neural network (ANN), and Fisher's discriminant analysis (FDA). Correct recognition ratio (CRR), area under the receiver operating characteristic curve (ROC), cumulative gains, and lift charts were used to evaluate the performance of models. The impact of different pretreatment methods on the models was explored, and pretreatment methods include Savitzky-Golay algorithm smoothing (SG), standard normal variate (SNV), multivariate scatter correction (MSC), and Savitzky-Golay algorithm 1st Derivative (SG 1st Der). In the DT, ANN, and FDA model, FDA is more robust for overfitting problem and offers the highest accuracy. Most pretreatment methods raised the performance of the models except SNV. The results revealed that CRM coupled with chemometrics offers a powerful tool for the discrimination of foodborne pathogenic bacteria.

Tracing Foodborne Botulism Events Caused by Clostridium botulinum in Xinjiang Province, China, Using a Core Genome Sequence Typing Scheme.

Foodborne botulism is a rare but life-threatening illness resulting from the action of a potent toxin mainly produced by Clostridium botulinum. It grows in an oxygen-deficient environment and is extremely viable in meat and soy products, making it one of the most virulent bacteria. How to track foodborne botulism events quickly and accurately has become a key issue. Here, we investigated two foodborne botulism events that occurred in Xinjiang in 2019 based on whole-genome sequencing and also successfully traced the relationship between clinical and food C. botulinum isolates using whole-genome core gene markers. All 59 isolates were classified as group I strains. Of the strains isolated in this study, 44 were found to be botulinum toxin A(B), and 15 isolates contained only the toxin B locus. Both the toxin A and B gene segments were located on the chromosome and organized in an ha cluster. Antibiotic resistance and virulence factors were also investigated. A set of 329 universal core gene markers were established using C. botulinum strains from a public database. These core gene markers were applied to the published C. botulinum genomes, and three outbreaks were identified. This work demonstrates that universal core gene markers can be used to trace foodborne botulism events, and we hope that our work will facilitate this effort in future. IMPORTANCE In this study, we analyzed 59 foodborne botulism (FB)-related strains isolated in Xinjiang Province, China. Our findings not only reveal the group classification, neurotoxin locus organization, antibiotic resistance and virulence factors of these strains but also establish a set of core gene markers for tracing foodborne botulism events, which was verified using published genomes. These findings indicate that these gene markers might be used as a potential tracing tool for FB events caused by C. botulinum group I strains, which have relatively stable genomic components.

Aqueous microsolvation of 4-hydroxy-2-butanone: competition between intra- and inter-molecular hydrogen bonds.

The rotational spectra of 4-hydroxy-2-butanone and its monohydrate were investigated by Fourier transform microwave spectroscopy complemented by quantum chemical calculations. One conformer of 4-hydroxy-2-butanone, with the intramolecular O-H⋯O hydrogen bond, has been observed in the pulsed jet. Rotational spectra of the six isotopologues (including four 13C and one 18O mono-substitution species) in natural abundance were measured and assigned, enabling the accurate structural determination of the molecular skeleton. The most stable isomer of its monohydrate, in which water inserts into the intramolecular hydrogen bond and serves the dual role of being a proton donor and acceptor, was also detected. The rotational spectra of HOD, DOH, D2O and H218O isotopologues were also measured allowing the accurate evaluation of the parameters of the intermolecular hydrogen bonds. This rotational spectroscopic investigation demonstrates that upon complexation, the weak intramolecular hydrogen bond in the monomer is replaced by two strong intermolecular O-H⋯O hydrogen bonds, leading to a change in the orientation of the -OH group of 4-hydroxy-2-butanone.

Rotational spectrum of anisole-CO2: Cooperative C···O tetrel bond and CH···O hydrogen bond.

Rotational spectrum of the 1:1 anisole-CO2 complex has been investigated using a pulsed jet Fourier transform microwave spectrometer supplemented with quantum chemical calculations. In the pulsed jet, only one isomer has been observed which is characterized by a dominant C···O tetrel bond and two CH···OCO2 weak hydrogen bonds. Different theoretical methods predict different orders of relative energies of plausible conformations. The experimental observation is most consistent with the theoretical estimation at the B3LYP-D3(BJ)/6-311++G(d,p) level of theory. Johnson's non-covalent interaction, quantum theory of atoms in molecules and natural bond orbital analyses have been applied to better understand the nature of non-covalent interactions at play in the anisole-CO2 complex.

Evaluation and Optimization of Microdrop Digital PCR for Detection of Serotype A and B Clostridium botulinum.

Clostridium botulinum is the causative pathogen of botulism. Laboratory detection of C. botulinum is essential for clinical therapy treatment of botulism due to the difficulty in diagnosis, especially in infant botulism. The extreme toxicity of botulinum neurotoxin (BoNT) requires a sensitive detection method. Due to the detection limit of real-time quantitative PCR (q-PCR), a more sensitive detection method, micro-drop digital PCR (ddPCR) was applied in C. botulinum main serotypes A and B. The following performance criteria were evaluated by ddPCR: analytical sensitivity; repeatability; and diagnostic specificity. The limit of detection (LOD) was 0.84 and 0.88 copies/µl for BoNT A and B genes, respectively, by ddPCR with high specificity, compared to 5.04×102 and 6.91×102 copies/µl by q-PCR. It was increased 10 times compared with q-PCR in spiked stool samples. This improvement in sensitivity was especially important in clinical samples as more positive samples were detected by digital PCR compared with q-PCR. Meanwhile, enrichment time for low bacteria content samples was shortened by four hours both in serotypes A and B C. botulinum by ddPCR compared with q-PCR, which are important for laboratory diagnosis and epidemiology work.

Laboratory Measurements and Astronomical Search for Methoxyacetone and Methyl Methoxyacetate.

High-resolution pure rotational spectra of methoxyacetone and methyl methoxyacetate have been recorded and analyzed by using pulsed jet-expansion Fourier transform microwave spectroscopy with the aid of quantum calculations. The global minima for both target molecules have been detected in pulsed jet, whose spectra are featured with the splittings raised from the methyl internal rotations. On the basis of the spectroscopic results, a radio-astronomical search of methoxyacetone and methyl methoxyacetate was carried out toward the high-mass star-forming region Sgr B2(N) using the Shanghai Tianma 65 m radio telescope. No lines belonging to either of the target molecules were detected, and the upper limits to the column density were derived.