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OBJECTIVE: Since January 8, 2023, China has managed COVID-19 as a Class-B infectious disease, marking the epidemic's transition to a low-level stage. This study analyzes the relationship between the public's perceived a community with shared future for doctor-patient (PCSF), health self-consciousness, benefit finding, and anxiety in this stage. Additionally, it compares changes in these variables across different stages of COVID-19. METHODS: Using a repeated cross-sectional design, three surveys were conducted respectively in three different stages of COVID-19 in China. Specifically, the first survey was conducted in Beijing, Dalian, Zhengzhou, Heihe, and Shangrao from November 13 to 20, 2021 in the outbreak stage of COVID-19, yielding 1,252 valid responses out of 1,534 collected questionnaires. The second survey was conducted in Dalian, Zhengzhou, Heihe, Shangrao, and Lanzhou from December 1 to 19, 2021 in the stable stage of COVID-19, with 872 valid responses obtained from 1,075 collected questionnaires. The third survey was conducted in Beijing, Dalian, Zhengzhou, Heihe, Shangrao, Lanzhou, and Chengdu from January 29 to February 4, 2023 in the low epidemic level stage of COVID-19, achieving 2,113 valid responses from the 2,461 questionnaires collected. RESULTS: Unlike in the outbreak stage but similar to the stable stage, the public's anxiety, health self-consciousness and benefit finding decreased while PCSF was improved in the low epidemic level stage. Consistent with both the outbreak and stable stage, PCSF, health self-consciousness, benefit finding, and anxiety showed positive correlations in the low epidemic level stage, with health self-consciousness partially mediating the positive impact of PCSF on benefit finding. Unlike in the stable stage but similar to the outbreak stage, anxiety did not moderate the relationship between PCSF and health self-consciousness in the low epidemic level stage. CONCLUSIONS: The public's health self-consciousness, benefit finding, and anxiety decreased, while PCSF increased in the low epidemic level stage. Furthermore, PCSF had a greater impact on benefit finding, and anxiety's impact on health self-consciousness was significantly reduced. Across different stages of COVID-19, PCSF directly increased benefit finding and also enhanced benefit finding by improving health self-consciousness. Thus, comprehensive intervention measures are beneficial in the low epidemic level stage.
Subject(s)
Anxiety , COVID-19 , Humans , COVID-19/psychology , COVID-19/epidemiology , Cross-Sectional Studies , Male , Pilot Projects , Female , Adult , China/epidemiology , Anxiety/psychology , Anxiety/epidemiology , Middle Aged , Young Adult , Surveys and Questionnaires , Physician-Patient Relations , SARS-CoV-2 , Adolescent , AgedABSTRACT
Objective: The prevalence of depression in children with severe bronchial asthma is a significant concern due to its potential effects on illness burden and quality of life. This cross-sectional study aims to explore the relationship between depression and severe bronchial asthma in children, focusing on the impact of alexithymia and somatic symptoms. Methods: The study includes a total of 186 children aged 6-14 years diagnosed with severe bronchial asthma between 2008 and 2022 in our institute. Alexithymia was assessed using the Toronto Alexithymia Scale-20 items (TAS-20). Somatization symptoms were measured using the children's somatization inventory (CSI). The Hamilton depression scale (HAMD) was used to evaluate depression. Spearman correlation analysis was used to describe the correlation between alexithymia, somatization symptoms, and depression. Results: Children with bronchial asthma are found to have a significantly higher prevalence of depression, estimated to be around 16.67%. Approximately 98.92% of children exhibit varying degrees of somatic symptoms. Approximately 3.23% of children have alexithymia. The Spearman correlation analysis revealed that somatic symptoms and alexithymia were positive correlated with the depression. The correlation coefficients were 0.986 and 0.981 (P < .01), respectively. moreover, according to the results of multiple linear regression analysis, somatization symptoms and alexithymia significantly affects depression in children with severe bronchitis asthma (P < .01). Conclusion: These findings suggest that children with severe bronchial asthma experience a higher prevalence of depression, impacting their overall quality of life. In addition, the presence of somatic symptoms is prevalent among these children, further contributing to the burden on their quality of life. Moreover, somatization symptoms and alexithymia have been identified as a significant factor positive affecting depression in this population. Addressing these factors in clinical interventions may be beneficial for improving the overall well-being in this population.
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Photothermal therapy synergized with photodynamic therapy for the treatment of tumors has emerged as a promising strategy. However, designing photosensitizers with both high photothermal efficiency and high photodynamic performance remains challenging. In contrast, the strategy of rationalizing the design of photosensitizers using the physiological properties of tumors to improve the photon utilization of photosensitizers during phototherapy is more advantageous than the approach of endowing a single photosensitizer with complex functions. Herein, we propose a molecular design (CyNP) to convert from photothermal therapy to photodynamic synergistic photothermal therapy based on the prevalent properties of hypoxic tumors. In the normoxic region of tumors, the deactivation pathway of CyNP excited state is mainly the conversion of photon energy to thermal energy; in the hypoxic region of tumors, CyNP is reduced to CyNH by nitroreductase, and the deactivation pathway mainly includes radiation leap, energy transfer between CyNP and oxygen, and conversion of photons energy to heat energy. This strategy enables real-time fluorescence detection of hypoxic tumors, and it also provides dual-mode treatment for photothermal and photodynamic therapy of tumors, achieving good therapeutic effects in vivo tumor treatment. Our study achieves more efficient tumor photoablation and provides a reference for the design ideas of smart photosensitizers.
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A metal-free cascade of α-acyloxylation/carboxamidation of I(III)/S(VI)-ylides, carboxylic acids, and isonitriles via a Passerini-like multicomponent reaction is reported. Unexpectedly, [3 + 1+1] cyclization involving I(III)/S(VI)-ylides and two molecules of ethyl isocyanoacetate was observed. The strategy allows for the synthesis of unsymmetrical α,α-disubstituted ketones and functionalized pyrroles with up to 99% yield and wide substrate compatibility. Notably, the procedure has been extended to the late-stage modification of drugs and natural products, offering an elegant complement to the classic Passerini reaction.
ABSTRACT
Chemosensory protein (CSP) genes significantly enriched in the female antennae are potential molecular candidates for mediating female oviposition behaviors. In this study, we presented the interaction mechanisms of a female-antenna-biased PxutCSP19 in Papilio xuthus to 47 host volatiles, four biopesticides and 24 synthetic insecticides. Using a bioinformatics-based homology search, 22 genes orthologous to PxutCSP19 were identified from 22 other Papilio butterflies with high sequence identities to each other (73.20~98.72%). Multiple alignment analyses revealed a particularly extended N-terminus of Papilio CSP19s (an average of 154 residues) compared to insects' typical CSPs (approximately 120 residues). The expression profiles indicated that PxutCSP19 was significantly enriched in the female antennae, with a 31.81-fold difference relative to the male antennae. In ligand-binding assays, PxutCSP19 could strongly bind six host odorants with high affinities, ranging from dissociation constant (Ki) values of 20.44 ± 0.64 µM to 22.71 ± 0.73 µM. Notably, this protein was tuned to a monoterpenoid alcohol, linalool, which generally existed in the Rutaceae plants and elicited electrophysiological and behavioral activities of the swallowtail butterfly. On the other hand, PxutCSP19 was also capable of binding eight insecticides with stronger binding abilities (Ki < 12 µM) compared to host odorants. When an extended N-terminal region of PxutCSP19 was truncated into two different proteins, they did not significantly affect the binding of PxutCSP19 to ligands with high affinities, suggesting that this extended N-terminal sequences were not involved in the specificity of ligand recognition. Altogether, our study sheds light on the putative roles of PxutCSP19 enriched in the female antennae of P. xuthus in the perception of host volatiles and the sequestering of insecticides, and it complements the knowledge of butterfly CSPs in olfaction and insecticide resistance.
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Background: Driver genes are essential predictors of targeted therapeutic efficacy. Detecting driver gene mutations in lung adenocarcinoma (LUAD) patients can help to screen for targeted drugs and improve patient survival benefits. This study aims to investigate the mutation characterization of driver genes and their correlation with clinicopathological features in LUAD. Methods: A total of 440 LUAD patients were selected from Sir Run Run Shaw Hospital between July 2019 and September 2022. Postoperative tissue specimens were analyzed for gene mutations using next-generation sequencing technology, focusing, including epidermal growth factor receptor EGFR, ALK, ROS1, RET, KRAS, MET, BRAF, HER2, PIK3CA and NRAS. At the same time, clinicopathological data were collected and organized for multidimensional correlation analysis. Results: Of 440 LUAD patients, driver gene mutations were not detected in 48 patients. The proportion of patients with driver gene mutations was as high as 89.09%. The top three driver genetic mutations were EGFR, KRAS, and MET. Sixty-nine types of EGFR mutations were detected and distributed in the protein tyrosine kinase catalytic domain (56, 81.16%), Furin-like cysteine-rich region (9, 13.04%), receptor binding domain (3, 4.35%), and EGFR transmembrane domain (1, 1.45%). Single gene locus mutation occurred in 343 LUAD patients, but the mutation gene types covered all tested genes. Our findings showed that EGFR mutations were more commonly observed in non-smoking and female patients (P<0.01), KRAS mutations were more prevalent in male patients and smokers (P<0.01), ROS1 mutations had larger tumor diameters (P<0.01) and RET mutations were more prevalent in smokers (P<0.05). Conclusions: LUAD patients exhibit diverse genetic mutations, which may co-occur simultaneously. Integrated analysis of multiple mutations is essential for accurate diagnosis and effective treatment of the disease. The use of NGS can significantly expand our understanding of gene mutations and facilitate integrated analysis of multiple gene mutations, providing critical evidence for targeted treatment methods.
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A practical strategy for the construction of diverse phosphonyl and thiofunctionalized sulfoxonium ylides via controllable monofunctionalization of hybrid I(III)/S(VI) ylides is presented. This process allows efficient P-H insertion of I(III)/S(VI) ylides under Cu catalysis, enabling the synthesis of phosphonyl sulfoxonium ylides, whereas reaction with sulfur-containing reagents including AgSCF3, KSC(S)OR, and KSCN under mild conditions resulted in α-trifluoromethylthiolation, dithiocarbanation, and thiocyanation of sulfoxonium ylides accordingly. Of note, wide substrate compatibility (108 examples), excellent efficiency (up to 99% yield), gram-scale experiments, and various product derivatizations highlight the synthetic utility of this protocol.
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One major obstacle in the treatment of cancer is the presence of proteins resistant to cancer therapy, which can impede the effectiveness of traditional approaches such as radiation and chemotherapy. This resistance can lead to disease progression and cause treatment failure. Extensive research is currently focused on studying these proteins to create tailored treatments that can circumvent resistance mechanisms. CLU (Clusterin), a chaperone protein, has gained notoriety for its role in promoting resistance to a wide range of cancer treatments, including chemotherapy, radiation therapy, and targeted therapy. The protein has also been discovered to have a role in regulating the immunosuppressive environment within tumors. Its ability to influence oncogenic signaling and inhibit cell death bolster cancer cells resistant against treatments, which poses a significant challenge in the field of oncology. Researchers are actively investigating to the mechanisms by which CLU exerts its resistance-promoting effects, with the ultimate goal of developing strategies to circumvent its impact and enhance the effectiveness of cancer therapies. By exploring CLU's impact on cancer, resistance mechanisms, tumor microenvironment (TME), and therapeutic strategies, this review aims to contribute to the ongoing efforts to improve cancer treatment outcomes.
Subject(s)
Clusterin , Drug Resistance, Neoplasm , Neoplasms , Tumor Microenvironment , Humans , Clusterin/metabolism , Neoplasms/immunology , Neoplasms/therapy , Neoplasms/drug therapy , Animals , Tumor Microenvironment/immunologyABSTRACT
Nirmatrelvir/ritonavir is a novel drug combination that is authorized by the Food and Drug Administration for the treatment of coronavirus disease 2019 (COVID-19). Ritonavir is a cytochrome P450 3A inhibitor and a P-glycoprotein inhibitor that increases the plasma concentration of tacrolimus and other medications. We describe the cases of two patients treated with nirmatrelvir/ritonavir: a patient who had undergone kidney transplantation and another with a history of hematopoietic stem cell transplantation. Toxic concentrations of tacrolimus were induced in both. This case series highlights the risk associated with the concomitant administration of tacrolimus and nirmatrelvir/ritonavir.
Subject(s)
COVID-19 Drug Treatment , Drug Interactions , Kidney Transplantation , Ritonavir , Tacrolimus , Humans , Ritonavir/therapeutic use , Tacrolimus/therapeutic use , Tacrolimus/adverse effects , Male , Middle Aged , SARS-CoV-2/isolation & purification , Female , Hematopoietic Stem Cell Transplantation , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/adverse effects , Cytochrome P-450 CYP3A Inhibitors/therapeutic use , Drug Combinations , COVID-19/virology , Aged , Antiviral Agents/therapeutic useABSTRACT
This research presents a new, eco-friendly, and swift method combining solid-phase extraction and hydrophobic deep eutectic solvents (DES) with high-performance liquid chromatography (SPE-DES-HPLC) for extracting and quantifying catechin and epicatechin in Shanxi aged vinegar (SAV). The parameters, such as the elution solvent type, the XAD-2 macroporous resin dosage, the DES ratio, the DES volume, the adsorption time, and the desorption time, were optimized via a one-way experiment. A central composite design using the Box-Behnken methodology was employed to investigate the effects of various factors, including 17 experimental runs and the construction of three-dimensional response surface plots to identify the optimal conditions. The results show that the optimal conditions were an HDES (tetraethylammonium chloride and octanoic acid) ratio of 1:3, an XAD-2 macroporous resin dosage of 188 mg, and an adsorption time of 11 min. Under these optimal conditions, the coefficients of determination of the method were greater than or equal to 0.9917, the precision was less than 5%, and the recoveries ranged from 98.8% to 118.8%. The environmentally friendly nature of the analytical process and sample preparation was assessed via the Analytical Eco-Scale and AGREE, demonstrating that this method is a practical and eco-friendly alternative to conventional determination techniques. In summary, this innovative approach offers a solid foundation for the assessment of flavanol compounds present in SAV samples.
Subject(s)
Acetic Acid , Catechin , Deep Eutectic Solvents , Hydrophobic and Hydrophilic Interactions , Solid Phase Extraction , Chromatography, High Pressure Liquid/methods , Solid Phase Extraction/methods , Acetic Acid/chemistry , Catechin/chemistry , Catechin/analysis , Deep Eutectic Solvents/chemistry , AdsorptionABSTRACT
The longhorned beetles are key players for the maintenance of biodiversity in the terrestrial ecosystem. As xylophagous cerambycid insects in Coleoptera, the beetles have evolved specialized olfactory and gustatory systems to recognize chemical cues in the surrounding habitats. Despite over 36,000 described species in the Cerambycidae family including a wood-boring pest Pharsalia antennata, only a limited number of them (<1 %) have been characterized regarding their chemical ecology at the molecular level. Here, we surveyed four membrane protein gene families in P. antennata related to chemoreception through transcriptomics, phylogenetics and expression profiling analyses. In total, 144 genes encoding 72 odorant receptors (ORs), 33 gustatory receptors (GRs), 23 ionotropic receptors (IRs), four sensory neuron membrane proteins (SNMPs) and 12 ionotropic glutamate receptors (iGluRs) were harvested from the transcriptome of multiple tissues including antennae and legs of both sexes. The lineage-specific expansion of PantORs possibly implied a diverse range of host plants in this beetle, supporting this correlation between the host range and olfactory receptor repertoire sizes across cerambycid species. Further phylogenetic analysis revealed that Group 2 was contributed mainly to the large OR gene repertoire in P. antennata, representing 18 genes in Group 2A and eight in Group 2B. On the other hand, some key chemosensory genes were identified by applying a phylogenetics approach, such as PantOR21 close to the 2-phenylethanol receptor in Megacyllene caryae, three carbon dioxide GRs and seven Antennal IRs (A-IRs) clades. We also determined sex- and tissue-specific expression profiles of 69 chemosensory genes, revealing the high expression of most PantORs in antennae. Noticeably, 10 sex-biased genes (six PantORs, three PantIRs and PantSNMP1a) were presented in antennae, five sex-biased PantGRs in legs and 39 sex-biased genes (15 PantORs, 13 PantGRs, eight PantIRs and three PantSNMPs) in abdomens. These findings have greatly enhanced our knowledge about the chemical ecology of P. antennata and identify candidate molecular targets for mediating smell and taste of this beetle.
Subject(s)
Coleoptera , Insect Proteins , Phylogeny , Animals , Coleoptera/genetics , Insect Proteins/genetics , Insect Proteins/metabolism , Receptors, Odorant/genetics , Receptors, Odorant/metabolism , Male , Membrane Proteins/genetics , Membrane Proteins/metabolism , Female , Transcriptome , Receptors, Ionotropic Glutamate/genetics , Receptors, Ionotropic Glutamate/metabolism , Multigene Family , Arthropod Antennae/metabolismABSTRACT
BACKGROUND: Coronavirus disease 2019 (COVID-19) has had global attention with regard to the urgent challenging threat to global public health. Currently, the novel Omicron variant is showing rapid transmission across the world, which appears to be more contagious than the previous variants of COVID-19. Early recognition of disease is critical for patients' prognosis. Fever is the most common symptom. We evaluated the clinical characteristics of febrile patients with COVID-19 reported in Suzhou and explored the predictors for a longer duration of hospitalization in febrile patients. METHODS: This retrospective study was carried out in 146 Omicron variant infected patients confirmed by nucleic acid tests in the Affiliated Infectious Hospital of Soochow University between February 13, 2022 and March 2, 2022. Data of febrile and afebrile laboratory-confirmed patients on hospital admission in Suzhou were collected and compared. According to the median length of stay (LOS), febrile cases were divided into short and long LOS groups. Then the predictive factors for a prolonged duration of hospitalization were analyzed using logistic regression methods. Receiver Operating Characteristic (ROC) Curve analysis was used to analyze the effectiveness of the risk factors for prolonged duration of hospitalization in febrile COVID-19 patients. RESULTS: Of the 146 discharged patients in our study, 112 patients (76.7%) caught a fever. Compared to afebrile Omicron patients, febrile patients showed a significantly longer duration of hospitalization (15.00 (5.80) vs. 13.00 (6.00), p = 0.002). Taking the median LOS (15 days) as the dividing point, 64 febrile cases were assigned to the short LOS group and the rest to the long LOS group. The long LOS group had a longer virus shedding duration than the short LOS group (18.42 ± 2.86 vs. 11.94 ± 2.50 days, p < 0.001). Compared to short LOS febrile patients, long LOS patients were older (44.88 ± 21.36 vs. 30.89 ± 17.95 years, p < 0.001) and showed a higher proportion of greater than 60 years old (33.3% vs. 9.4%, p = 0.002; Supplemental Table S2). Febrile patients with long LOS also showed a higher proportion of hypertension (25% vs. 6.3%, p = 0.005) and higher levels of cTnI (5.00 (3.00) vs. 4.00 (2.00) µg/L, p = 0.025). The multivariate analysis indicated that virus shedding duration (OR 2.369, 95% CI 1.684 - 3.333, p < 0.001) was the independent risk factor associated with long-term hospital stay in febrile patients with Omicron. Furthermore, ROC Curve analysis revealed that the area under the curve (AUC) for virus shedding duration to diagnose prolonged duration of hospitalization in febrile COVID-19 patients was 0.951 (95% CI 0.913 - 0.989). The cutoff point was set at 14.5 days. CONCLUSIONS: More than half of the non-severe patients exposed to the new Omicron variant had symptoms of fever. In total, 42.86% of the febrile patients were discharged within 15 days since hospital admission. Febrile Omicron cases took a longer duration of hospitalization compared to afebrile patients, and virus shedding duration (OR 2.369, 95% CI 1.684 - 3.333, p < 0.001) was probably a predictive factor for long-term hospital stays.
Subject(s)
COVID-19 , Fever , Length of Stay , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/diagnosis , Length of Stay/statistics & numerical data , Female , Male , Fever/epidemiology , Fever/diagnosis , Fever/virology , Retrospective Studies , Middle Aged , China/epidemiology , Adult , Risk Factors , AgedABSTRACT
Pectin, a natural polysaccharide, holds versatile applications in food and pharmaceuticals. However, there is a need for further exploration into extracting novel functional fractions and characterizing them thoroughly. In this study, a sequential extraction approach was used to obtain three distinct lemon pectin (LP) fractions from lemon peels (Citrus Eureka): LP extracted with sodium acetate (LP-SA), LP extracted with ethylenediaminetetraacetic acid (LP-EDTA), and LP extracted with sodium carbonate and sodium borohydride (LP-SS). Comprehensive analysis revealed low methyl-esterification in all fractions. LP-SA and LP-SS displayed characteristics of rhamnogalacturonan-I type pectin, while LP-EDTA mainly consisted of homogalacturonan pectin. Notably, LP-SA formed self-aggregated particles with rough surfaces, LP-EDTA showed interlocking linear structures with smooth planes, and LP-SS exhibited branch chain structures with smooth surfaces. Bioactivity analysis indicated that LP-SA had significant apparent viscosity and ABTS radical scavenging activity, while both LP-EDTA and LP-SS showed excellent thermal stability according to thermogravimetric analysis (TGA). Furthermore, LP-SS exhibited remarkable gel-forming ability and significant hydroxyl free radicals scavenging activity. In conclusion, this study presents a novel method for extracting various lemon pectin fractions with unique structural and bioactive properties, contributing insights for advanced applications in the food and pharmaceutical sectors.
Subject(s)
Antioxidants , Citrus , Pectins , Pectins/chemistry , Pectins/isolation & purification , Citrus/chemistry , Antioxidants/chemistry , Antioxidants/pharmacology , Antioxidants/isolation & purification , Chemical Phenomena , Viscosity , Fruit/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacologyABSTRACT
A novel dispersive solid-phase microextraction method based on a metal-organic framework (MIL-100(Fe)) combined with a dispersive liquid-liquid microextraction technique was proposed for the extraction and enrichment of four insecticides in beverages. The qualitative and quantitative analysis of these insecticides was conducted using HPLC-MS/MS. To optimize the extraction process, several parameters were investigated, and the main variables were optimized using CCD-based RSM. The developed method displayed a wide linear range of 1.000-1000 ng/L and R2 values >0.993 for all four calibration curves. The method demonstrated high sensitivity, with LODs and LOQs of 0.3-0.6 ng/L and 0.8-1.0 ng/L, respectively. In addition, the greenness of the proposed method was assessed using the Complex GAPI tool, and the results showed that the proposed method exhibits benefits, such as minimal usage of organic solvents and negligible matrix influence, making it a suitable method for the detection of insecticide residues in beverages.
Subject(s)
Beverages , Food Contamination , Insecticides , Liquid Phase Microextraction , Pesticide Residues , Solid Phase Microextraction , Tandem Mass Spectrometry , Liquid Phase Microextraction/methods , Chromatography, High Pressure Liquid , Insecticides/analysis , Insecticides/isolation & purification , Insecticides/chemistry , Pesticide Residues/analysis , Pesticide Residues/isolation & purification , Pesticide Residues/chemistry , Tandem Mass Spectrometry/methods , Food Contamination/analysis , Beverages/analysis , Solid Phase Microextraction/methods , Metal-Organic Frameworks/chemistry , Liquid Chromatography-Mass SpectrometryABSTRACT
G-protein-coupled receptors (GPCRs) transmit downstream signals predominantly via G-protein pathways. However, the conformational basis of selective coupling of primary G-protein remains elusive. Histamine receptors H2R and H3R couple with Gs- or Gi-proteins respectively. Here, three cryo-EM structures of H2R-Gs and H3R-Gi complexes are presented at a global resolution of 2.6-2.7 Å. These structures reveal the unique binding pose for endogenous histamine in H3R, wherein the amino group interacts with E2065.46 of H3R instead of the conserved D1143.32 of other aminergic receptors. Furthermore, comparative analysis of the H2R-Gs and H3R-Gi complexes reveals that the structural geometry of TM5/TM6 determines the primary G-protein selectivity in histamine receptors. Machine learning (ML)-based structuromic profiling and functional analysis of class A GPCR-G-protein complexes illustrate that TM5 length, TM5 tilt, and TM6 outward movement are key determinants of the Gs and Gi/o selectivity among the whole Class A family. Collectively, the findings uncover the common structural geometry within class A GPCRs that determines the primary Gs- and Gi/o-coupling selectivity.
Subject(s)
Cryoelectron Microscopy , Receptors, G-Protein-Coupled , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/chemistry , Receptors, G-Protein-Coupled/genetics , Humans , Cryoelectron Microscopy/methods , GTP-Binding Proteins/metabolism , GTP-Binding Proteins/chemistry , GTP-Binding Proteins/genetics , Histamine/metabolism , Histamine/chemistry , Receptors, Histamine H2/metabolism , Receptors, Histamine H2/genetics , Receptors, Histamine H2/chemistry , Receptors, Histamine H3/metabolism , Receptors, Histamine H3/chemistry , Receptors, Histamine H3/genetics , Signal TransductionABSTRACT
The gut microbiota of poultry is influenced by a variety of factors, including feed, drinking water, airborne dust, and footpads, among others. Gut microbiota can affect the immune reaction and inflammation in the lungs. To investigate the effect of gut microbiota variation on lung inflammation induced by PM2.5 (fine particulate matter) in broilers, 36 Arbor Acres (AA) broilers were randomly assigned to three groups: control group (CON), PM2.5 exposure group (PM), and PM2.5 exposure plus oral antibiotics group (PMA). We used non-absorbable antibiotics (ABX: neomycin and amikacin) to modify the microbiota composition in the PMA group. The intervention was conducted from the 18th to the 28th day of age. Broilers in the PM and PMA groups were exposed to PM by a systemic exposure method from 21 to 28 days old, and the concentration of PM2.5 was controlled at 2 mg/m3. At 28 days old, the lung injury score, relative mRNA expression of inflammatory factors, T-cell differentiation, and dendritic cell function were significantly increased in the PM group compared to the CON group, and those of the PMA group were significantly decreased compared to the PM group. There were significant differences in both α and ß diversity of cecal microbiota among these three groups. Numerous bacterial genera showed significant differences in relative abundance among the three groups. In conclusion, gut microbiota could affect PM2.5-induced lung inflammation in broilers by adjusting the capacity of antigen-presenting cells to activate T-cell differentiation. IMPORTANCE: Gut microbes can influence the development of lung inflammation, and fine particulate matter collected from broiler houses can lead to lung inflammation in broilers. In this study, we explored the effect of gut microbes modified by intestinal non-absorbable antibiotics on particulate matter-induced lung inflammation. The results showed that modification in the composition of gut microbiota could alleviate lung inflammation by attenuating the ability of dendritic cells to stimulate T-cell differentiation, which provides a new way to protect lung health in poultry farms.
Subject(s)
Chickens , Gastrointestinal Microbiome , Particulate Matter , Pneumonia , Poultry Diseases , Animals , Chickens/microbiology , Gastrointestinal Microbiome/drug effects , Poultry Diseases/microbiology , Poultry Diseases/prevention & control , Pneumonia/veterinary , Pneumonia/microbiology , Anti-Bacterial Agents/pharmacology , Housing, Animal , Lung/microbiology , Lung/drug effects , Bacteria/classification , Bacteria/isolation & purification , Bacteria/drug effects , Bacteria/geneticsABSTRACT
Major Depressive Disorder (MDD) is a widespread psychiatric condition that affects a significant portion of the global population. The classification and diagnosis of MDD is crucial for effective treatment. Traditional methods, based on clinical assessment, are subjective and rely on healthcare professionals' expertise. Recently, there's growing interest in using Resting-State Functional Magnetic Resonance Imaging (rs-fMRI) to objectively understand MDD's neurobiology, complementing traditional diagnostics. The posterior cingulate cortex (PCC) is a pivotal brain region implicated in MDD which could be used to identify MDD from healthy controls. Thus, this study presents an intelligent approach based on rs-fMRI data to enhance the classification of MDD. Original rs-fMRI data were collected from a cohort of 430 participants, comprising 197 patients and 233 healthy controls. Subsequently, the data underwent preprocessing using DPARSF, and the amplitudes of low-frequency fluctuation values were computed to reduce data dimensionality and feature count. Then data associated with the PCC were extracted. After eliminating redundant features, various types of Support Vector Machines (SVMs) were employed as classifiers for intelligent categorization. Ultimately, we compared the performance of each algorithm, along with its respective optimal classifier, based on classification accuracy, true positive rate, and the area under the receiver operating characteristic curve (AUC-ROC). Upon analyzing the comparison results, we determined that the Random Forest (RF) algorithm, in conjunction with a sophisticated Gaussian SVM classifier, demonstrated the highest performance. Remarkably, this combination achieved a classification accuracy of 81.9 % and a true positive rate of 92.9 %. In conclusion, our study improves the classification of MDD by supplementing traditional methods with rs-fMRI and machine learning techniques, offering deeper neurobiological insights and aiding accuracy, while emphasizing its role as an adjunct to clinical assessment.
Subject(s)
Depressive Disorder, Major , Gyrus Cinguli , Magnetic Resonance Imaging , Support Vector Machine , Humans , Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/classification , Gyrus Cinguli/diagnostic imaging , Gyrus Cinguli/physiopathology , Female , Male , Adult , Middle Aged , Case-Control Studies , Young Adult , AlgorithmsABSTRACT
Tianwang Buxin Pills have demonstrated therapeutic effects in clinical practice, whereas there is a serious lack of comprehensive quality control to ensure the safety and effectiveness of clinical medication. In this study, ultra-performance liquid chromatography(UPLC) was employed to establish the fingerprint and the method for simultaneously determining the content of seven components of Tianwang Buxin Pills. Furthermore, chemometrics was employed to identify the key factors for the stable quality, which provided a reference for the comprehensive quality control and evaluation of this preparation. There were 25 common peaks in the UPLC fingerprints of 15 batches of Tianwang Buxin Pills, from which thirteen compounds were identified. A quantitation method was established for seven pharmacological components(α-linolenic acid, salvianolic acid B, glycyrrhetinic acid, schisandrin A, ß-asarone, 3,6'-disinapoylsucrose, and ligustilide). The principal component analysis(PCA) and partial least square discriminate analysis(PLS-DA) were performed to determine the key pharmacological components for controlling the quality stability of Tianwang Buxin Pills, which included 3,6'-disinapoylsucrose, α-linolenic acid, and ß-asarone. The established fingerprint and multi-component content determination method have strong specificity, stability, and reliability. In addition, 3,6'-disinapoylsucrose, α-linolenic acid, and ß-asarone are the key pharmacological components that ensure the quality stability between batches and can be used to comprehensively control the quality of Tianwang Buxin Pills. The findings provide a scientific basis for the quality evaluation and standard establishment of Tianwang Buxin Pills.
Subject(s)
Allylbenzene Derivatives , Anisoles , Coumaric Acids , Drugs, Chinese Herbal , Sucrose/analogs & derivatives , Drugs, Chinese Herbal/pharmacology , Chromatography, High Pressure Liquid , Reproducibility of Results , alpha-Linolenic Acid , Quality ControlABSTRACT
The processing and analysis of massive high-dimensional datasets are important issues in precision livestock farming (PLF). This study explored the use of multivariate analysis tools to analyze environmental data from multiple sensors located throughout a broiler house. An experiment was conducted to collect a comprehensive set of environmental data including particulate matter (TSP, PM10, and PM2.5), ammonia, carbon dioxide, air temperature, relative humidity, and in-cage and aisle wind speeds from 60 locations in a typical commercial broiler house. The dataset was divided into 3 growth phases (wk 1-3, 4-6, and 7-9). Spearman's correlation analysis and principal component analysis (PCA) were used to investigate the latent associations between environmental variables resulting in the identification of variables that played important roles in indoor air quality. Three cluster analysis methods; k-means, k-medoids, and fuzzy c-means cluster analysis (FCM), were used to group the measured parameters based on their environmental impact in the broiler house. In general, the Spearman and PCA results showed that the in-cage wind speed, aisle wind speed, and relative humidity played critical roles in indoor air quality distribution during broiler rearing. All 3 clustering methods were found to be suitable for grouping data, with FCM outperforming the other 2. Using data clustering, the broiler house spaces were divided into 3, 2, and 2 subspaces (clusters) for wk 1 to 3, 4 to 6, and 7 to 9, respectively. The subspace in the center of the house had a poorer air quality than other subspaces.