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Cutibacterium granulosum, a commensal bacterium found on human skin, formerly known as Propionibacterium granulosum, rarely causes infections and is generally considered non-pathogenic. Recent research has revealed the transferability of the multidrug-resistant plasmid pTZC1 between C. granulosum and Cutibacterium acnes, the latter being an opportunistic pathogen in surgical site infections. However, there is a noticeable lack of research on the genome of C. granulosum, and the genetic landscape of this species remains largely uncharted. We investigated the genomic features and evolutionary structure of C. granulosum by analyzing a total of 30 Metagenome-Assembled Genomes (MAGs) and isolate genomes retrieved from public databases, as well as those generated in this study. A pan-genome of 6,077 genes was identified for C. granulosum. Remarkably, the 'cloud genes' constituted 62.38% of the pangenome. Genes associated with mobilome: prophages, transposons [X], defense mechanisms [V] and replication, recombination and repair [L] were enriched in the cloud genome. Phylogenomic analysis revealed two distinct mono-clades, highlighting the genomic diversity of C. granulosum. The genomic diversity was further confirmed by the distribution of Average Nucleotide Identity (ANI) values. The functional profiles analysis of C. granulosum unveiled a wide range of potential Antibiotic Resistance Genes (ARGs) and virulence factors, suggesting its potential tolerance to various environmental challenges. Subtype I-E of the CRISPR-Cas system was the most abundant in these genomes, a feature also detected in C. acnes genomes. Given the widespread distribution of C. granulosum strains within skin microbiome, our findings make a substantial contribution to our broader understanding of the genetic diversity, which may open new avenues for investigating the mechanisms and treatment of conditions such as acne vulgaris. [ABSTRACT FROM AUTHOR]

In this study, tert-butyl 4-(5-bromopyridin-2-yloxy)piperidine-1-carboxylate was synthesized. The title compound was characterized using ¹H NMR, 13C NMR, MS, and FT-IR techniques, and its single crystal was evaluated using X-ray diffraction (XRD). The molecular structure was optimized using the density functional theory (DFT) at the B3LYP/6-311+G(2d, p) level. The optimized structure was also compared with the crystal structure determined using single-crystal (XRD), and the results were consistent. Molecular electrostatic potential (MEP) and frontier molecular orbital (FMOs) analyses of the title compound were preformed using computational methods. Infrared vibrational analysis of the target compound was also conducted. [ABSTRACT FROM AUTHOR]

In this study, tert-butyl 4-(5-bromopyridin-2-yloxy)piperidine-1-carboxylate was synthesized. The title compound was characterized using ¹H NMR, 13C NMR, MS, and FT-IR techniques, and its single crystal was evaluated using X-ray diffraction (XRD). The molecular structure was optimized using the density functional theory (DFT) at the B3LYP/6-311 + G(2d, p) level. The optimized structure was also compared with the crystal structure determined using single-crystal (XRD), and the results were consistent. Molecular electrostatic potential (MEP) and frontier molecular orbital (FMOs) analyses of the title compound were preformed using computational methods. Infrared vibrational analysis of the target compound was also conducted. [ABSTRACT FROM AUTHOR]

Neural networks and deep learning have been successfully applied to tackle problems in drug discovery with increasing accuracy over time. There are still many challenges and opportunities to improve molecular property predictions with satisfactory accuracy even further. Here, we proposed a deep-learning architecture model, namely Bidirectional long short-term memory with Channel and Spatial Attention network (BCSA), of which the training process is fully data-driven and end to end. It is based on data augmentation and SMILES tokenization technology without relying on auxiliary knowledge, such as complex spatial structure. In addition, our model takes the advantages of the long- and short-term memory network (LSTM) in sequence processing. The embedded channel and spatial attention modules in turn specifically identify the prime factors in the SMILES sequence for predicting properties. The model was further improved by Bayesian optimization. In this work, we demonstrate that the trained BSCA model is capable of predicting aqueous solubility. Furthermore, our proposed method shows noticeable superiorities and competitiveness in predicting oil–water partition coefficient, when compared with state-of-the-art graphs models, including graph convoluted network (GCN), message-passing neural network (MPNN), and AttentiveFP. [ABSTRACT FROM AUTHOR]

Under the framework of growth accounting, this paper introduces four heterogeneity characteristics of labor, namely, educational level, age, gender and industry, constructs a cross classification matrix of employment, labor compensation and working hours, and calculates the labor input (volume) of the whole country and of 19 industries during 2000-2018. Then it decomposes the volume into quantity and quality parts to analyze the total amount of labor input and the performance of industry labor input. The results are as follows. First, during the research period, the annual growth rate of labor input was 2.5%, and 78.8% of that came from the growth of labor input quality. The growth of labor input was mainly resulted from the improvement of educational level and the optimization of industrial structure. Second, in 2018, the proportions of labor input of the primary, secondary and tertiary sectors were 13.76%, 31.06% and 55.18% respectively, and the transfer speed of labor input to the secondary and tertiary sectors was higher than that of the quantity structure; the labor input volume in the new economy and related industries in the tertiary sector has been greatly increased. Third, the index method-based labor productivity (ILP) of some producer service and consumer service industries was relatively low, and the growth of total industry output mainly attributed to the increase of labor input and the expansion of industrial scale. The improvement of labor input quality has become the key to the growth of labor input in China, and the improvement of educational level is the core power to improve the labor input quality. [ABSTRACT FROM AUTHOR]

Background: Hypothyroidism in the first trimester of pregnancy (T1) has great adverse effects on mothers and foetuses. However, few studies have investigated the influence on postpartum thyroid dysfunction. This study aimed to evaluate their long-term effect on postpartum thyroid function within one year after delivery. Methods: In total, 151 women were recruited from 1496 participants and were classified as newly diagnosed subclinical hypothyroidism (SCH) in T1 (ND-SCH, n=50), previously known SCH before pregnancy (PK-SCH, n=51) and previously known overt hypothyroidism (PK-OH, n=50). Their thyroid functions were dynamically monitored from pre-conception to one-year postpartum. Results: During pregnancy, the first thyroid functions’ test time in T1 were 5-8 gestational weeks. After delivery, the prevalence of postpartum thyroiditis (PPT) was comparable in women with previously known and newly diagnosed hypothyroidism [ND-SCH 62.0% vs PK-SCH 64.7% vs PK-OH 64.0%, P=0.96]. For the ND-SCH group, PPT was significantly related with thyroid-stimulating hormone (TSH) >4.0 mU/L occurring at <8 gestational weeks [OR=8.06, 95% CI, 2.08-31.29] and TSH levels outside 1.0-2.5 mU/L near childbirth [OR=3.73, 95% CI, 1.04-13.41]. For patients with known hypothyroidism before pregnancy (PK-SCH and PK-OH), TSH>2.5 mU/L in T1 [OR=3.55, 95% CI, 1.43-8.81] and TPOAb≥300 μIU/mL [OR=6.58, 95% CI, 2.05-21.12] were associated with PPT. Regardless of whether SCH was diagnosed before pregnancy or in T1, the levothyroxine (LT4) treatment was discontinued at delivery. More than 50% of the patients had to face the hypothyroidism phase of postpartum and restarted LT4 treatment in the first-year follow-up. The logistic regression analysis revealed that TSH elevation occurring at <8 gestational weeks [OR=2.48, 95% CI, 1.09-5.6], TSH levels outside 1.0-2.5 mU/L near childbirth [OR=3.42, 95% CI, 1.45-8.05], and TPOAb≥300 μIU/mL [OR=6.59, 95% CI, 1.79-24.30] were the risk factors. Conclusion: TSH elevation at <8 gestational weeks was associated with PPT after delivery in women with known and newly diagnosed hypothyroidism. Especially for SCH patients who stopped LT4 treatment at delivery, unsatisfactory TSH level at <8 gestational weeks and near childbirth, TPOAb≥300 μIU/mL were the risk factors for LT4 retreatment in one-year postpartum. [ABSTRACT FROM AUTHOR]

Objective of this study was to observe the clinical effect of mesalazine combined with bifid triple viable (BTV) on ulcerative colitis. One hundred sixty patients with ulcerative colitis were divided into the experimental group accepting mesalazine combined with BTV and the control group accepting mesalazine alone. It was found that the overall treatment effective rate was 93.75%, in the experimental group as against 77.50% in the control group, p<0.05. Comparing the levels of inflammatory factors (IL-6,IL-8,TNF-a) before and after treatment in the two groups, the improvement degree of the experimental group after treatment was significantly better than that of the control group, p<0.05. The overall nursing satisfaction of the research group was 97.50%, which was significantly higher than the 75.00% of the control group, p<0.05. To conclude that combined therapy of mesalazine and BTV can significantly improve the therapeutic effect in patients with ulcerative colitis, and the scientific nursing mode is an important guarantee to improve the therapeutic results. [ABSTRACT FROM AUTHOR]

Background. Gestational diabetes mellitus (GDM) severely threatens maternal and fetal health. Long non-coding RNA (lncRNA) participates in the regulation of various cellular processes. Objectives. Previous studies have identified the role of lncRNA MALAT1 in diabetic retinopathy-related inflammation. However, the role of lncRNA MALAT1 in GDM has not been reported yet. Material and methods. Real-time polymerase chain reaction (RT-PCR) was used to measure the lncRNA MALAT1 expression level in placental tissues from GDM patients and from a normal pregnant group. Placental trophoblastic-derived cell line HTR8 cells were divided into a control group, an siRNA negative control group and a MALAT1 siRNA group. The cells underwent RT-PCR analysis of lncRNA MALAT1 expression, an MTT assay of cell proliferation, and a transwell assay of cell invasion and migration. In addition, enzyme-linked immunosorbent assay (ELISA) was used to analyze the level of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6). Western blotting was used to measure the changes of the tumor growth factor β (TGF-β)/nuclear factor-kappa B (NF-κ B) signaling pathway. Results. Gestational diabetes mellitus placental tissues showed higher lncRNA MALAT1 expression compared to a normal control group (p < 0.05). After siRNA intervention, lncRNA MALAT1 showed decreased expres- sion in the trophoblastic layer; inhibited trophoblastic cell proliferation, migration, or invasion; decreased the secretion of inflammatory factors TNF-α and IL-6; and suppressed the expression of TGF-β and NF-κ B compared to that of the control and siRNA-NC groups (p < 0.05). Conclusions. Gestational diabetes mellitus appears to upregulate lncRNA MALAT1. Downregulation of lncRNA MALAT1 inhibits inflammation and suppresses the proliferation, invasion and migration of GDM placental trophoblastic cells, possibly by modulating the TGF-β/NF-κ B signaling pathway. [ABSTRACT FROM AUTHOR]

Ribonuclease 9 (RNase 9) is a member of the ribonuclease A superfamily, which is mainly expressed in the epididymis. However, it has no ribonucleolytic activity and its function remains unclear. Immunofluorescence experiments showed that the localization of RNase 9 protein on the sperm surface has moved from the neck to the acrosome cap during capacitation and acrosome reaction. Chlortetracycline staining was used to assay the role of RNase 9 on capacitation and acrosome reaction. The spontaneous acrosome reaction induced by progesterone could be suppressed by RNase 9 protein and the acrosome reaction ratio was 6.5±1.2%. Furthermore, exposure of spermatozoa to RNase 9 protein reduced the level of cyclic AMP significantly during the acrosome reaction. Taken together, we confirmed that RNase 9 protein could impair sperm function, including capacitation and acrosome reaction, and had potential role in male reproductive toxicity. [ABSTRACT FROM AUTHOR]

Background: Inflammasomes, which mediate maturation of interleukin-1β (IL-β) and interleukin-18 (IL-18) and lead to pyroptosis, have been linked to various autoimmune disorders. This study investigated whether they are involved in the pathogenesis of autoimmune thyroiditis (AIT). Methods: We collected thyroid tissues from 50 patients with AIT and 50 sex- and age-matched controls. Serum levels of free T3, free T4, thyrotropin, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured by electrochemiluminescent immunoassays. Expression of several inflammasome components, the NOD-like receptor (NLR) family pyrin domain containing 1 (NLRP1), NLRP3, CARDdomain containing 4 (NLRC4), absent in melanoma 2 (AIM2), the apoptosis-associated speck-like protein that contains a caspase recruitment domain (ASC), caspase-1, IL-1β, and IL-18 was determined by real-time PCR and western blot. Immunohistochemistry was used to localize the expression of NLRP1, NLRP3, NLRC4, and AIM2. The Nthy-ori 3-1 thyroid cell line was stimulated with tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-17A, interleukin-6, and poly(dA:dT). The levels of IL-18 and IL-1β in the cell supernatant were measured by enzyme-linked immunosorbent assay, and lactate dehydrogenase was quantified by absorptiometry. ASC specks were examined by confocal immunofluorescence microscopic analysis. Cell death was examined by flow cytometry, and the N-terminal domain of gasdermin D was detected by western blot analysis. Results: Expression of NLRP1, NLRP3, NLRC4, AIM2, ASC, caspase-1, pro IL-1β, pro IL-18, mRNA, and protein was significantly increased in thyroid tissues from patients with AIT, and enhanced posttranslational maturation of caspase-1, IL-18 and IL-1β was also observed. Expression of NLRP1, NLRP3, NLRC4, and AIM2 was localized mainly in thyroid follicular cells adjacent to areas of lymphatic infiltration. The thyroid mRNA level of NLRP1 and ASC was correlated to the serum TPOAb and TgAb levels in the AIT group. TNF-α and IFN-γ had a priming effect on the expression of multiple inflammasome components in thyroid cells. IFN-γ was found to strengthen poly(dA:dT)-induced cell pyroptosis and bioactive IL-18 release. Conclusion: Our work has demonstrated for the first time that multiple inflammasomes are associated with AIT pathogenesis. The identified NLRP3, NLRP1, NLRC4, AIM2 inflammasomes and their downstream cytokines may represent potential therapeutic targets and biomarkers of AIT. [ABSTRACT FROM AUTHOR]

Background: Tracking targets of natural products is one of the most challenging issues in fields ranging from pharmacognosy to biomedicine. It is widely recognized that the biocompatible nanoparticle (NP) could function as a 'key' that opens the target 'lock'. Results: We report a functionalized poly-lysine NP technique that can monitor the target protein of arctigenin (ATG) in vivo non-invasively. The NPs were synthesized, and their morphologies and surface chemical properties were characterized by transmission electron microscopy (TEM), laser particle size analysis and atomic force microscopy (AFM). In addition, we studied the localization of ATG at the level of the cell and the whole animal (zebrafish and mice). We demonstrated that fluorescent NPs could be ideal carriers in the development of a feasible method for target identification. The distributions of the target proteins were found to be consistent with the pharmacological action of ATG at the cellular and whole-organism levels. [ABSTRACT FROM AUTHOR]

Background: Traditional Chinese medicine (TCM) herbal formulae provide valuable therapeutic strategies. However, the active ingredients and mechanisms of action remain unclear for most of these formulae. Therefore, the identification of complex mechanisms is a major challenge in TCM research. Methods: This study used a network pharmacology approach to clarify the anti-inflammatory and cough suppressing mechanisms of the Chinese medicinal preparation Eriobotrya japonica - Fritillaria usuriensis dropping pills (ChuanbeiPipa dropping pills, CBPP). The chemical constituents of CBPP were identified by high-quality ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS), and anti-inflammatory ingredients were selected and analyzed using the PharmMapper and Kyoto Encyclopedia of Genes and Genomes (KEGG) bioinformatics websites to predict the target proteins and related pathways, respectively. Then, an RNA-sequencing (RNA-Seq) analysis was carried out to investigate the different expression of genes in the lung tissue of rats with chronic bronchitis. Results: Six main constituents affected 19 predicted pathways, including ursolic acid and oleanolic acid from Eriobotrya japonica (Thunb.) Lindl. (Eri), peiminine from Fritillaria usuriensis Maxim. (Fri), platycodigenin and polygalacic acid from Platycodon grandiflorum (Jacq.) A. DC. (Pla) and guanosine from Pinellia ternata (Thunb.) Makino. (Pin). Expression of 34 genes was significantly decreased after CBPP treatment, affecting four therapeutic functions: immunoregulation, anti-inflammation, collagen formation and muscle contraction. Conclusion: The active components acted on the mitogen activated protein kinase (MAPK) pathway, transforming growth factor (TGF)-beta pathway, focal adhesion, tight junctions and the action cytoskeleton to exert anti-inflammatory effects, resolve phlegm, and relieve cough. This novel approach of global chemomics-integrated systems biology represents an effective and accurate strategy for the study of TCM with multiple components and multiple target mechanisms. [ABSTRACT FROM AUTHOR]

Background: Rhizoma Menispermi (RM) is the dried root of Menispermum dauricum DC, which is traditionally used to treat swelling and pain for sore throat, enteritis and rheumatic arthralgia in the clinic, but its bioactive compounds remain unclear. Methods: In this study, RM extract was administered orally to ICR mice followed by challenging with an intratracheal Pseudomonas aeruginosa suspension. Then mortality, histological features of lung, and inflammatory cytokines were evaluated. RM treatment significantly ameliorated Pseudomonas aeruginosa-induced acute lung inflammation and reduced levels of inflammatory mediators. To screen for potential anti-inflammatory constituents of the RM extract, a simple and rapid method based on ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) coupled with a luciferase reporter assay system to detect nuclear factor-κB (NF-κB) activity was established. Results: Using this system, seven potential NF-κB inhibitors were detected, including sinomenine, norsinoacutin, N-norsinoacutin-β-D-glucopyranoside, 6-O-methyl-laudanosoline-13-O-glucopyranoside, magnoflorine, laurifloline and dauricinoline. Furthermore, IL-6 and IL-8 assays confirmed the anti-inflammatory effects of these potential NF-κB inhibitors, in which norsinoacutin, 6-O-methyl-laudanosoline-13-O-glucopyranoside laurifloline, dauricinoline and N-norsinoacutin-β-D-glucopyranoside were revealed as new NF-κB inhibitors. Conclusion: This method of UPLC-Q/TOF coupled with the luciferase reporter assay system was initially applied to the study of RM and was demonstrated to represent a simple, rapid and practical approach to screen for anti-inflammatory compounds. This study provided useful results for further investigation on the anti-inflammatory mechanism of RM. [ABSTRACT FROM AUTHOR]

Glycyrrhetic acid (GA) exerts synergistic anti-asthmatic effects via a β2-adrenergic receptor (β2AR)-mediated pathway. Cholesterol is an important component of the structure and function of lipid rafts, which play critical roles in the β2AR-Gs-adenylate cyclase (AC)-mediated signaling pathway. Owing to the structural similarities between GA and cholesterol, we investigated the possibility that GA enhances β2AR signaling by altering cholesterol distribution. Azide-terminal GA (ATGA) was synthesized and applied to human embryonic kidney 293 (HEK293) cells expressing fusion β2AR, and the electron spin resonance (ESR) technique was utilized. GA was determined to be localized predominantly on membrane and decreased their cholesterol contents. Thus, the fluidity of the hydrophobic region increased but not the polar surface of the cell membrane. The conformations of membrane proteins were also changed. GA further changed the localization of Gαs from lipid rafts to non-raft regions, resulting the binding of β2AR and Gαs, as well as in reduced β2AR internalization. Co-localization of β2AR, Gαs, and AC increased isoproterenol-induced cAMP production and cholesterol reloading attenuated this effect. A speculation wherein GA enhances beta-adrenergic activity by increasing the functional linkage between the subcomponents of the membrane β2AR-protein kinase A (PKA) signaling pathway was proposed. The enhanced efficacy of β2AR agonists by this novel mechanism could prevent tachyphylaxis. [ABSTRACT FROM AUTHOR]

C60 nanorods in two polymeric phases have been synthesized under different high pressure and high temperature conditions. Orthorhombic and tetragonal phases have been identified from Raman spectra. The rod shape can be kept under quasihydrostatic pressure. The photoluminescence intensity of the polymeric C60 nanorods has been greatly enhanced compared with that of pristine C60 nanorods. The main fluorescence band shifted from 730 nm in the unpolymeric phase to 748 nm and near infrared 780 nm in the orthorhombic and tetragonal phases, respectively. The enhanced photoluminescence with tunable frequency for different polymeric C60 nanorods suggests potential applications in luminescent nanomaterials. [ABSTRACT FROM AUTHOR]

The controllable synthesis of ZnS nanocrystals with desirable morphology and correlative structure has been carried out via the solvothermal method by simply changing the molar ratio of the reactants. The hexagonal-shaped ZnS nanosheets with a zinc-blende structure were synthesized in one step for the first time. ZnS nanorods with wurtzite structure and large ratio of length to diameter were also fabricated. We found that phase transformation is easily induced and there is a strong correlation between the morphology and structure of the ZnS nanocrystals by changing the ratio of the reactants. The photoluminescence spectra of the ZnS nanosheets and nanorods exhibit different emission bands. ZnS nanosheets show a strong emission at 534 nm while the nanorods have two emissions located at 520 and 578 nm. [ABSTRACT FROM AUTHOR]