Genome enrichment of rare and unknown species from complicated microbiomes by nanopore selective sequencing.

Rare species are vital members of a microbial community, but retrieving their genomes is difficult because of their low abundance. The ReadUntil (RU) approach allows nanopore devices to sequence specific DNA molecules selectively in real time, which provides an opportunity for enriching rare species. Despite the robustness of enriching rare species by reducing the sequencing depth of known host sequences, such as the human genome, there is still a gap in RU-based enriching of rare species in environmental samples whose community composition is unclear, and many rare species have poor or incomplete reference genomes in public databases. Therefore, here we present metaRUpore to overcome this challenge. When we applied metaRUpore to a thermophilic anaerobic digester (TAD) community and human gut microbial community, it reduced coverage of the high-abundance populations and modestly increased (∼2×) the genome coverage of the rare taxa, facilitating successful recovery of near-finished metagenome-assembled genomes (nf-MAGs) of rare species. The simplicity and robustness of the approach make it accessible for laboratories with moderate computational resources, and hold the potential to become the standard practice in future metagenomic sequencing of complicated microbiomes.

Ripretinib inhibits HIV-1 transcription through modulation of PI3K-AKT-mTOR.

Despite the effectiveness of antiretroviral therapy (ART) in prolonging the lifespan of individuals infected with HIV-1, it does not offer a cure for acquired immunodeficiency syndrome (AIDS). The "block and lock" approach aims to maintain the provirus in a state of extended transcriptional arrest. By employing the "block and lock" strategy, researchers endeavor to impede disease progression by preventing viral rebound for an extended duration following patient stops receiving ART. The crux of this strategy lies in the utilization of latency-promoting agents (LPAs) that are suitable for impeding HIV-1 provirus transcription. However, previously documented LPAs exhibited limited efficacy in primary cells or samples obtained from patients, underscoring the significance of identifying novel LPAs that yield substantial outcomes. In this study, we performed high-throughput screening of FDA-approved compound library in the J-Lat A2 cell line to discover more efficacious LPAs. We discovered ripretinib being an LPA candidate, which was validated and observed to hinder proviral activation in cell models harboring latent infections, as well as CD4+ T cells derived from infected patients. We demonstrated that ripretinib effectively impeded proviral activation through inhibition of the PI3K-AKT-mTOR signaling pathway in the HIV-1 latent cells, thereby suppressing the opening states of cellular chromatin. The results of this research offer a promising drug candidate for the implementation of the "block and lock" strategy in the pursuit of an HIV-1 cure.

Mechanisms of isomerization and hydration reactions of typical ß-diketone at the air-droplet interface.

Acetylacetone (AcAc) is a typical class of ß-diketones with broad industrial applications due to the property of the keto-enol isomers, but its isomerization and chemical reactions at the air-droplet interface are still unclear. Hence, using combined molecular dynamics and quantum chemistry methods, the heterogeneous chemistry of AcAc at the air-droplet interface was investigated, including the attraction of AcAc isomers by the droplets, the distribution of isomers at the air-droplet interface, and the hydration reactions of isomers at the air-droplet interface. The results reveal that the preferential orientation of two AcAc isomers (keto- and enol-AcAc) to accumulate and accommodate at the acidic air-droplet interface. The isomerization of two AcAc isomers at the acidic air-droplet interface is more favorable than that at the neutral air-droplet interface because the "water bridge" structure is destroyed by H3O+, especially for the isomerization from keto-AcAc to enol-AcAc. At the acidic air-droplet interface, the carbonyl or hydroxyl O-atoms of two AcAc isomers display an energetical preference to hydration. Keto-diol is the dominant products to accumulate at the air-droplet interface, and excessive keto-diol can enter the droplet interior to engage in the oligomerization. The photooxidation reaction of AcAc will increase the acidity of the air-droplet interface, which indirectly facilitate the uptake and formation of more keto-diol. Our results provide an insight into the heterogeneous chemistry of ß-diketones and their influence on the environment.

[Risk factors for the failure of ibuprofen treatment in preterm infants with hemodynamically significant patent ductus arteriosus]. / æœ‰è¡€æµåŠ¨åŠ›å­¦æ„ä¹‰çš„åŠ¨è„‰å¯¼ç®¡æœªé—­æ—©äº§å„¿å¸ƒæ´›èŠ¬æ²»ç–—å¤±è´¥çš„å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To investigate the risk factors for the failure of ibuprofen treatment in preterm infants with hemodynamically significant patent ductus arteriosus (hsPDA). METHODS: A retrospective collection of clinical data was conducted on preterm infants with a gestational age of <34 weeks who were diagnosed with hsPDA and treated at the Department of Neonatology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, from January 2018 to June 2023. The subjects were divided into two groups based on the treatment approach: the ibuprofen group (95 cases) and the ibuprofen plus surgery group (44 cases). The risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA were identified by binary logistic regression analysis. RESULTS: The binary logistic regression analysis revealed that an increased diameter of the ductus arteriosus, a resistance index (RI) value of the middle cerebral artery ≥0.80, and prolonged total invasive mechanical ventilation time were risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA (P<0.05). Receiver operating characteristic curve analysis showed that a ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days had significant predictive value for the failure of ibuprofen treatment in preterm infants with hsPDA (P<0.05). The combined predictive value of these three factors was the highest, with an area under the curve of 0.843, a sensitivity of 86.5%, and a specificity of 75.0% (P<0.05). CONCLUSIONS: A ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days are risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA, and they are of significant predictive value for the necessity of surgical treatment following the failure of ibuprofen treatment.

Ponatinib Represses Latent HIV-1 by Inhibiting AKT-mTOR.

Although antiretroviral therapy (ART) is effective in suppressing viral replication, it does not cure HIV-1 infection due to the presence of the viral latent reservoir. Rather than reactivating the latent viruses, the "block and lock" strategy aims to shift the viral reservoir to a deeper state of transcriptional silencing, thus preventing viral rebound after ART interruption. Although some latency-promoting agents (LPAs) have been reported, none of them have been approved for clinical application due to cytotoxicity and limited efficacy; therefore, it is important to search for novel and effective LPAs. Here, we report an FDA-approved drug, ponatinib, that can broadly repress latent HIV-1 reactivation in different cell models of HIV-1 latency and in primary CD4+ T cells from ART-suppressed individuals ex vivo. Ponatinib does not change the expression of activation or exhaustion markers on primary CD4+ T cells and does not induce severe cytotoxicity and cell dysfunction. Mechanistically, ponatinib suppresses proviral HIV-1 transcription by inhibiting the activation of the AKT-mTOR pathway, which subsequently blocks the interaction between key transcriptional factors and the HIV-1 long terminal repeat (LTR). In summary, we discovered a novel latency-promoting agent, ponatinib, which could have promising significance for future applications of HIV-1 functional cure.

Design, synthesis and evaluation of a series of novel long-acting dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is one of the most popular chronic diseases around the whole world. To improve the compliance of patients, long-acting antidiabetic drugs needed to be developed. Dipeptidyl peptidase-4 (DPP-4) inhibitors are becoming increasingly important in the T2DM treatment due to the favorable properties. In the present study, a series of new substituted dihydropyrido [4',3':3,4] pyrazolo [1,5-a] pyrimidin-9(10H)-yl)-2-(2,5-difluorophenyl)tetrahydro-2H-pyran-3-amine were designed and synthesized as potent DPP-4 inhibitors. All compounds were characterized by 1H NMR, 13C NMR and HRMS and were evaluated in vitro. The inhibitory activity ranged from 0.43 to 12.70 µM while the inhibitory activity of positive control (omarigliptin) was 3.63 µM on DPP-4 in Caco-2 cells. Then pharmacokinetic studies were carried out in rats and compound 6c was finally selected for the further study because of its better pharmacokinetic profile. Additionally, preclinical pharmacological study of compound 6c exhibited extraordinary efficacy in vivo and good safety profile. In conclusion, compound 6c was considered as a promising DPP-4 inhibitor, which could be taken once a week or once every two weeks for the treatment of T2DM. More comprehensive researches will be carried out in the future for the further development of compound 6c.

Quantification of perception towards facial skin ideal complexion in multiple ethnic populations from clinical imaging cues.

OBJECTIVE: Ideal complexion is a perceptual skin quality that is strongly influenced by cultural and ethnic background. The objectives of this study are to quantitatively characterise skin ideal complexion based on clinical image cues and to compare the perceptions of ideal complexion among multiple ethnicities. METHODS: Facial images of Indian, Chinese, Caucasian and Latino females collected using VISIA®-CR were presented to naïve panels of the same ethnicity following a two-alternative forced choice design and responses on skin 'ideal complexion' were obtained from 336 panellists. Panel perception was transformed logistically (d') and projected onto a continuum (ω) following Bradley-Terry model. Image cues including skin colour and unevenness, skin shine and surface smoothness and pigmentary blotches and spots were computed using image analysis, and their relationship with ω was evaluated through multiple regression analysis. A novel skin index, namely ideal complexion score (ICS), was developed and correlated against age using linear regression. Finally, ICS was applied to evaluate treatment efficacy of a skin brightening kit on 35 female Caucasian subjects. RESULTS: Panel perception d' showed statistically significant (p < 0.05) correlation with the contrast of image cues for all ethnic panels (R2  = 0.74, 0.76, 0.62 and 0.46 for Indian, Chinese, Caucasian and Latino respectively) and strong correlations between perception ω and linear combinations of image cues were observed (R2 > 0.88 for all). Main effects of facial image visual cues on ideal complexion were compared: contrast of skin redness and pigmented spots and visual smoothness were important in determining ICS for all ethnicities; skin colour unevenness was more pronounced for Indian and Caucasian; skin lightness was important for Indian and Chinese; skin shine was critical for Chinese and Latino; and skin hue angle ranked higher for Caucasian. Correlations between ICS and age were observed for Indian and Caucasian (R2  = 0.55) in which ICS decreased as age increased. Twenty-nine percent improvement on ICS was observed after 12 weeks' treatment using the brightening kit compared with the baseline. CONCLUSION: Mathematical models were successfully established to describe subjective perception towards skin ideal complexion based on objectively measured image cues for multiple ethnicities.

OBJECTIF: Le teint idéal est une qualité de peau perceptuelle qui est fortement influencée par l'origine culturelle et ethnique. Les objectifs de cette étude consistent à caractériser quantitativement le teint idéal de la peau en se basant sur des repères d'image clinique et à comparer les perceptions du teint idéal parmi plusieurs origines ethniques. MÉTHODES: Des images faciales de femmes indiennes, chinoises, caucasiennes et latino-américaines recueillies à l'aide de VISIA®-CR ont été présentées à des panels naïfs de même origine ethnique, suivant une conception à choix forcé en deux alternatives, et les réponses concernant le «teint idéal¼ de la peau ont été obtenues de 336 membres du panel. La perception du panel a été transformée sur le plan logistique (d') et projetée sur un continuum (ω) selon le modèle de BradleyTerry. Les repères d'image, y compris la couleur, l'uniformité et la brillance de la peau, et la douceur de la surface de la peau, ainsi que les taches et rougeurs pigmentaires, ont été calculés à l'aide d'une analyse d'image, et leur relation avec ω a été évaluée par le biais d'une analyse de régression multiple. Un nouvel indice cutané, à savoir le score de teint idéal (STI), a été développé et corrélé à l'âge à l'aide d'une régression linéaire. Enfin, un STI a été appliqué pour évaluer l'efficacité du traitement d'un kit d'éclaircissement de la peau chez 35 sujets caucasiens de sexe féminin. RÉSULTATS: La perception du panel d' a montré une significativité statistique (p de 0.88 pour tous). Les principaux effets des repères visuels de l'image faciale sur le teint idéal ont été comparés : le contraste des rougeurs cutanées, les taches pigmentées et la douceur visuelle étaient importants pour déterminer les STI pour toutes les origines ethniques; l'inégalité de la couleur de la peau était plus prononcée pour les Indiens et les Caucasiens; la luminosité de la peau était importante pour les Indiens et les Chinois ; et l'angle de teinte de la peau était plus élevée pour les sujets caucasiens. Des corrélations entre les STI et l'âge ont été observées pour les populations indienne et caucasienne (R2  = 0.55) chez lesquelles les STI ont diminué avec l'âge. Une amélioration de vingt-neuf pour cent des STI a été observée après 12 semaines de traitement à l'aide du kit d'éclaircissement par rapport à la référence. CONCLUSION: Des modèles mathématiques ont été établis avec succès afin de décrire la perception subjective du teint idéal de la peau sur la base d'indices d'image mesurés objectivement pour plusieurs origines ethniques.

Comprehensive model for characterizing skin translucency by expert grading, panel evaluation and image analysis in a Chinese population.

OBJECTIVES: Translucent skin is an attribute widely appreciated by people in East Asian countries. There have been studies in the literature to describe the phenomenon by means of clinical grading, instrumental measurement and image analysis. However, due to its subjective and complex nature, skin translucency has not been comprehensively and rigorously characterized and modelled, particularly in the Chinese population. This study is to develop a mathematical model that quantitatively describes skin translucency from visual cues objectively measured from the skin. MATERIALS AND METHODS: The study was designed to characterize and model skin translucency by incorporating expert evaluation, panel perception and image analysis of multiple skin visual attributes in one analysis. Faces of 36 Chinese females aged 18-65 years old were evaluated by a dermatologist to obtain clinical translucency scores. Subject pairs were formed with a relatively high and low translucency score in each pair. Their faces were judged in person by 9 panellists in paired-comparison (2-AFC) fashion to pick a 'more translucent skin' from each subject pair. Front-view facial images of the subjects were taken, and multiple colour and other visually perceivable skin attributes were measured using image analysis. Bradley-Terry analysis and multiple regressions were performed to correlate the panel choices of 'more translucent skin' with the objectively measured skin parameters. RESULTS: Multiple skin colour properties affected the panel choices towards translucent skin. Among them skin tone lightness and skin glossiness had positive effects on skin translucency while the hue, colour unevenness, severity of red and dark spots affected it negatively. Subsurface light reflection and skin visual smoothness had some effect but were not statistically significant. A mathematical model was constructed to predict a person's skin translucency from objectively measured skin attributes. CONCLUSION: The subjective property of skin translucency can be characterized and quantified via a comprehensive modelling process involving clinical grading, panel evaluation, image-based measurement of skin attributes and statistical analysis. A novel skin parameter, Skin Translucency Index (STI) was established, which provides a way to measure skin translucency, making it possible to assess treatment efficacy before and after product application.

OBJECTIF: La peau translucide est un attribut largement apprécié dans les pays d'Asie de l'Est. Des études ont été menées dans la littérature pour décrire ce phénomène au moyen d'une classification clinique, d'une mesure instrumentale et d'une analyse d'images. Cependant, en raison de sa nature subjective et complexe, la translucidité de la peau n'a pas été caractérisée et modélisée de manière exhaustive et rigoureuse, en particulier dans la population chinoise. Cette étude vise à développer un modèle mathématique qui décrit quantitativement la translucidité de la peau à partir de repères visuels objectivement mesurés sur la peau. MATÉRIELS ET MÉTHODES: L'étude a été conçue pour caractériser et modéliser la translucidité de la peau en intégrant l'évaluation des experts, les perceptions d'un panel et l'analyse d'images de multiples attributs visuels de la peau dans une seule analyse. Les visages de 36 femmes chinoises âgées de 18 à 65 ans ont été évalués par un dermatologue afin d'obtenir des scores de translucidité clinique. Des paires de sujets ont été formées, chaque paire ayant un score de translucidité relativement élevé et faible. Leurs visages ont été jugés en personne par 9 panellistes en comparaison appariée (2-AFC) pour choisir une « peau plus translucide ¼ pour chaque paire de sujets. Des images des visages des sujets de face ont été prises, et des attributs liés aux couleurs et d'autres attributs cutanés perceptibles visuellement ont été mesurés par une analyse des images. Une analyse de Bradley-Terry et des régressions multiples ont été réalisées pour corréler les choix de « peau plus translucide ¼ par le panel avec les paramètres cutanés mesurés objectivement. RÉSULTATS: Plusieurs propriétés liées à la couleur de peau ont influencé les choix du panel vers une peau translucide. Parmi celles-ci, la pâleur du teint et la brillance de la peau ont eu des effets positifs sur la translucidité de la peau, tandis que la teinte, l'inégalité de la couleur, la sévérité des taches rouges et foncées ont exercé une influence défavorable. La réflexion de la lumière sous la surface et la douceur de la peau perçue visuellement ont eu un certain effet, mais n'étaient pas statistiquement significatives. Un modèle mathématique a été construit pour prédire la translucidité de la peau d'une personne à partir d'attributs cutanés mesurés objectivement. CONCLUSION: La propriété subjective de la translucidité de la peau peut être caractérisée et quantifiée via un processus de modélisation complet comprenant une classification clinique, une évaluation par un panel, une mesure basée sur les images d'attributs cutanés et une analyse statistique. Un nouveau paramètre cutané, l'indice de translucidité de la peau (ITP), a été établi, qui fournit un moyen de mesurer la translucidité de la peau, permettant d'évaluer l'efficacité du traitement avant et après l'application du produit.

[Metabolomic changes of neonatal sepsis: an exploratory clinical study]. / æ–°ç”Ÿå„¿è´¥è¡€ç—‡çš„ä»£è°¢ç»„å­¦æ”¹å˜ï¼šä¸€é¡¹æŽ¢ç´¢æ€§ä¸´åºŠç ”ç©¶.

OBJECTIVES: To study the metabolic mechanism of neonatal sepsis at different stages by analyzing the metabolic pathways involving the serum metabolites with significant differences in neonates with sepsis at different time points after admission. METHODS: A total of 20 neonates with sepsis who were hospitalized in the Department of Neonatology, Hunan Provincial People's Hospital, from January 1, 2019 to January 1, 2020 were enrolled as the sepsis group. Venous blood samples were collected on days 1, 4, and 7 after admission. Ten healthy neonates who underwent physical examination during the same period were enrolled as the control group. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used for the metabonomic analysis of serum samples to investigate the change in metabolomics in neonates with sepsis at different time points. RESULTS: On day 1 after admission, the differentially expressed serum metabolites between the sepsis and control groups were mainly involved in the biosynthesis of terpenoid skeleton. For the sepsis group, the differentially expressed serum metabolites between days 1 and 4 after admission were mainly involved in pyruvate metabolism, and those between days 4 and 7 after admission were mainly involved in the metabolism of cysteine and methionine. The differentially expressed serum metabolites between days 1 and 7 after admission were mainly involved in ascorbic acid metabolism. CONCLUSIONS: The metabolic mechanism of serum metabolites varies at different stages in neonates with sepsis and is mainly associated with terpenoid skeleton biosynthesis, pyruvate metabolism, cysteine/methionine metabolism, and ascorbic acid metabolism.

A metagenomic-based method to study hospital air dust resistome.

As a symbol of the defense mechanisms that bacteria have evolved over time, the genes that make bacteria resist antibiotics are overwhelmingly present in the environment. Currently, bacterial antibiotic resistance genes (ARGs) in the air are a serious concern. Previous studies have identified bacterial communities and summarized putative routes of transmissions for some dominant hospital-associated pathogens from hospital indoor samples. However, little is known about the possible indoor air ARG transportation. In this study, we mainly surveyed air-conditioner air dust samples under different airflow conditions and analyzed these samples using a metagenomic-based method. The results show air dust samples exhibited a complex resistome, and the average concentration is 0.00042 copies/16S rRNA gene, which is comparable to some other environments. The hospital air-conditioners can form resistome over time and accumulate pathogens. In addition, our results indicate that the Outpatient hall is one of the main ARG transmission sources, which can distribute ARGs to other departments (explains >80% resistome). We believe that the management should focus on ARG carrier genera such as Staphylococcus, Micrococcus, Streptococcus, and Enterococcus in this hospital and our novel evidence-based network strategy proves that plasmid-mediated ARG transfer can occur frequently. Overall, these results provide insights into the characteristics of air dust resistome and possible route for how ARGs are spread in air.

Indoles from commensal bacteria extend healthspan.

Multiple studies have identified conserved genetic pathways and small molecules associated with extension of lifespan in diverse organisms. However, extending lifespan does not result in concomitant extension in healthspan, defined as the proportion of time that an animal remains healthy and free of age-related infirmities. Rather, mutations that extend lifespan often reduce healthspan and increase frailty. The question arises as to whether factors or mechanisms exist that uncouple these processes and extend healthspan and reduce frailty independent of lifespan. We show that indoles from commensal microbiota extend healthspan of diverse organisms, including Caenorhabditis elegans, Drosophila melanogaster, and mice, but have a negligible effect on maximal lifespan. Effects of indoles on healthspan in worms and flies depend upon the aryl hydrocarbon receptor (AHR), a conserved detector of xenobiotic small molecules. In C. elegans, indole induces a gene expression profile in aged animals reminiscent of that seen in the young, but which is distinct from that associated with normal aging. Moreover, in older animals, indole induces genes associated with oogenesis and, accordingly, extends fecundity and reproductive span. Together, these data suggest that small molecules related to indole and derived from commensal microbiota act in diverse phyla via conserved molecular pathways to promote healthy aging. These data raise the possibility of developing therapeutics based on microbiota-derived indole or its derivatives to extend healthspan and reduce frailty in humans.

[Dyspnea and ventilator dependence after birth in a full-term female infant].

A female infant, aged 43 days, had shortness of breath, cyanosis, groan, and dyspnea since birth. Physical examination showed cyanosis of lips and three-concave sign, and multiple lung imaging examinations showed diffuse ground-glass opacities in both lungs. The girl was given anti-infective therapy and continuous mechanical ventilation but there were no significant improvements in symptoms. Gene testing confirmed a compound heterozygous mutation, c.1890C>A(p.Tyr630Ter)+c.3208G>A(p.Ala1070Thr), in the ABCA3 gene, with the former from her father and the latter from her mother. Pathological examination of the lungs indicated pulmonary interstitial disease. The girl was diagnosed with infantile diffuse pulmonary interstitial disease caused by mutations in the ABCA3 gene. When full-term neonates experience shortness of breath and dyspnea after birth, pulmonary imaging suggests diffuse ground-glass changes, and conventional treatment is not effective (ventilator-dependent), congenital pulmonary surfactant metabolism defects needs to be considered. Gene testing, which can provide a basis for early intervention, prognostic evaluation, and genetic counseling, should be performed as early as possible.

S100A9 gene silencing inhibits the release of pro-inflammatory cytokines by blocking the IL-17 signalling pathway in mice with acute pancreatitis.

The study aimed to investigate whether S100A9 gene silencing mediating the IL-17 pathway affected the release of pro-inflammatory cytokines in acute pancreatitis (AP). Kunming mice were assigned to the normal, AP, AP + negative control (NC), AP + shRNA, AP + IgG and AP + anti IL-17 groups. ELISA was applied to measure expressions of AMY, LDH, CRP, TNF-α, IL-6 and IL-8. The cells were distributed into the control, blank, NC, shRNA1 and shRNA2 groups. MTT assay, flow cytometry, RT-qPCR and Western blotting were used to evaluate cell proliferation, cell cycle and apoptosis, and expressions of S100A9, TLR4, RAGE, IL-17, HMGB1 and S100A12 in tissues and cells. Compared with the normal group, the AP group displayed increased expressions of AMY, LDH, CRP, TNFα, IL-6, IL-8, S100A9, TLR4, RAGE, IL-17, HMGB1 and S100A12. The AP + shRNA and AP + anti IL-17 groups exhibited an opposite trend. The in vivo results: Compare with the control group, the blank, NC, shRNA1 and shRNA2 groups demonstrated increased expressions of S100A9, TLR4, RAGE, IL-17, HMGB1 and S100A12, as well as cell apoptosis and cells at the G1 phase, with reduced proliferation. Compared with the blank and NC groups, the shRNA1 and shRNA2 groups had declined expressions of S100A9, TLR4, RAGE, IL-17, HMGB1 and S100A12, as well as cell apoptosis and cells at the G1 phase, with elevated proliferation. The results indicated that S100A9 gene silencing suppressed the release of pro-inflammatory cytokines through blocking of the IL-17 pathway in AP.

Two-bubble acoustic tweezing cytometry for biomechanical probing and stimulation of cells.

The study of mechanotransduction relies on tools that are capable of applying mechanical forces to elicit and assess cellular responses. Here we report a new (to our knowledge) technique, called two-bubble acoustic tweezing cytometry (TB-ATC), for generating spatiotemporally controlled subcellular mechanical forces on live cells by acoustic actuation of paired microbubbles targeted to the cell adhesion receptor integrin. By measuring the ultrasound-induced activities of cell-bound microbubbles and the actin cytoskeleton contractile force responses, we determine that TB-ATC elicits mechanoresponsive cellular changes via cyclic, paired displacements of integrin-bound microbubbles driven by the attractive secondary acoustic radiation force (sARF) between the bubbles in an ultrasound field. We demonstrate the feasibility of dual-mode TB-ATC for both subcellular probing and mechanical stimulation. By exploiting the robust and unique interaction of ultrasound with microbubbles, TB-ATC provides distinct advantages for experimentation and quantification of applied forces and cellular responses for biomechanical probing and stimulation of cells.

Deciphering the adaptation mechanism of anammox consortia under sulfamethoxazole stress: A model coupling resistance accumulation and interspecies-cooperation.

Sulfamethoxazole (SMX) is frequently detected in wastewater where anammox applications are promising. While it has been demonstrated that anammox consortia can adapt to SMX stress, the underlying community adaptation strategy has not yet been fully addressed. Therefore, in this study, we initially ascertained anammox consortia's ability to co-metabolize SMX in batch tests. Then, a 200-day domestication process of anammox consortia under SMX stress was carried out with community variations and transcriptional activities monitored by metagenomic and metatranscriptomic sequencing techniques. Despite the initial drop to 41.88 %, the nitrogen removal efficiency of the anammox consortia rebounded to 84.64 % post-domestication under 5 mg/L SMX. Meanwhile, a 4.85-fold accumulation of antibiotic resistance genes (ARGs) under SMX stress was observed as compared to the control group. Interestingly, the anammox consortia may unlock the SMX-inhibited folate synthesis pathway through a novel interspecies cooperation triangle among Nitrospira (NAA), Desulfobacillus denitrificans (DSS1), and the core anammox population Candidatus Brocadia sinica (AMX1), in which the modified dihydropteroate synthase (encoded by sul1) of NAA reconnected the symbiotic cooperation between AMX1 and DSS1. Overall, this study provides a new model for the adaptation strategies of anammox consortia to SMX stress.

Systematic evaluation of the impact of standard storage conditions on plasmid conjugation behavior in wastewater samples.

Filter mating experiment is widely used to study the conjugation behavior of plasmids and associated antibiotic resistance in environmental settings, however, the influence and biases brought by sample storage conditions (temperature and duration) were not yet systematically elaborated. This study systematically investigated the influence of standard storage conditions (4 °C, -20 °C, -80 °C) on plasmid conjugation behavior in influent (Inf) and activated sludge (AS) samples from sewage treatment plants (STP). The findings revealed a significant reduction in conjugation efficiency under all the tested storage conditions except for 1-week storage at 4 °C. Notably, storing at -80 °C maintained conjugation activities in activated sludge more effectively compared to -20 °C. However, the preservation performance was less effective for influent samples, which consist mainly of anaerobe-dominant communities. Systematic loss of IncH-type plasmids was observed in influent samples stored at 4 °C and -20 °C. Correspondingly, the plasmid-carrying resistome genotypes detected in the influent samples showed a clear downward trend with the increase in storage duration when stored at 4 °C and -20 °C. A relatively uniform composition in terms of incompatibility type and resistome profile was observed across activated sludge samples, regardless of the varied storage conditions. This study highlights the critical impact of storage conditions on plasmid conjugation behavior and resistome composition, offering valuable insights for optimal sample handling in resistome research.

Temperature-responsive salt-resistant poly(sulfobetaine methacrylate)-based emulsifiers for heavy oils.

The emulsions prepared with most currently reported emulsifiers are stable only at room temperature and are susceptible to demulsification at higher temperatures. This thermal instability prevents their use in high-temperature and high-salt environments encountered oilfield extraction. To address this issue, in this study, two temperature-responsive emulsifiers, PSBMA and CS-PSBMA, were synthesized. Both emulsifiers exhibited the ability to form stable emulsions within the temperature range of 60-80 °C and undergo demulsification at 20-40 °C. A comprehensive investigation was conducted to assess the impact of emulsifier concentration, water-to-oil ratio, and salt ion concentration on the stability of emulsions formed by these two emulsifiers. The results demonstrated their remarkable emulsification capabilities across diverse oil phases. Notably, the novel emulsifier CS-PSBMA, synthesized through the grafting chitosan (CS) onto PSBMA, not only exhibits superior emulsion stability and UCST temperature responsiveness but also significantly enhanced the salt resistance of the emulsion. Remarkably, the emulsion maintained its stability even in the presence of monovalent salt ions at concentrations up to 2 mol/L (equivalent to a mineralization level of 1.33 × 105 mg/L in water) and divalent salt ions at concentrations up to 3 mol/L (equivalent to a mineralization level of 2.7 × 105 mg/L in water). The emulsions stabilized by both emulsifiers are resilient to harsh reservoir conditions and effectively emulsify heavy oils, enabling high-temperature emulsification and low-temperature demulsification. These attributes indicate their promising potential for industrial applications, particularly in the field of enhanced oil recovery.

PGAM5 knockout causes depressive-like behaviors in mice via ATP deficiency in the prefrontal cortex.

INTRODUCTION: Major depressive disorder (MDD) affects about 17% population in the world. Although abnormal energy metabolism plays an important role in the pathophysiology of MDD, however, how deficiency of adenosine triphosphate (ATP) products affects emotional circuit and what regulates ATP synthesis are still need to be elaborated. AIMS: Our study aimed to investigate how deficiency of PGAM5-mediated depressive behavior. RESULTS: We firstly discovered that PGAM5 knockout (PGAM5-/- ) mice generated depressive-like behaviors. The phenotype was reinforced by the observation that chronic unexpected mild stress (CUMS)-induced depressive mice exhibited lowered expression of PGAM5 in prefrontal cortex (PFC), hippocampus (HIP), and striatum. Next, we found, with the using of functional magnetic resonance imaging (fMRI), that the functional connectivity between PFC reward system and the PFC volume were reduced in PGAM5-/- mice. PGAM5 ablation resulted in the loss of dendritic spines and lowered density of PSD95 in PFC, but not in HIP. Finally, we found that PGAM5 ablation led to lowered ATP concentration in PFC, but not in HIP. Coimmunoprecipitation study showed that PGAM5 directly interacted with the ATP F1 F0 synthase without influencing the interaction between ATP F1 F0 synthase and Bcl-xl. We then conducted ATP administration to PGAM5-/- mice and found that ATP could rescue the behavioral and neuronal phenotypes of PGAM5-/- mice. CONCLUSIONS: Our findings provide convincing evidence that PGAM5 ablation generates depressive-like behaviors via restricting neuronal ATP production so as to impair the number of neuronal spines in PFC.

The application of hospitality elements in hospitals.

In the last decade, many hospital designs have taken inspiration from hotels, spurred by factors such as increased patient and family expectations and regulatory or financial incentives. Increasingly, research evidence suggests the value of enhancing the physical environment to foster healing and drive consumer decisions and perceptions of service quality. Although interest is increasing in the broader applicability of numerous hospitality concepts to the healthcare field, the focus of this article is design innovations, and the services that such innovations support, from the hospitality industry. To identify physical hotel design elements and associated operational features that have been used in the healthcare arena, a series of interviews with hospital and hotel design experts were conducted. Current examples and suggestions for future hospitality elements were also sought from the experts, academic journals, and news articles. Hospitality elements applied in existing hospitals that are addressed in this article include hotel-like rooms and decor; actual hotels incorporated into medical centers; hotel-quality food, room service, and dining facilities for families; welcoming lobbies and common spaces; hospitality-oriented customer service training; enhanced service offerings, including concierges; spas or therapy centers; hotel-style signage and way-finding tools; and entertainment features. Selected elements that have potential for future incorporation include executive lounges and/or communal lobbies with complimentary wireless Internet and refreshments, centralized controls for patients, and flexible furniture. Although the findings from this study underscore the need for more hospitality-like environments in hospitals, the investment decisions made by healthcare executives must be balanced with cost-effectiveness and the assurance that clinical excellence remains the top priority.

Neuronal Response to Reward and Luminance in Macaque LIP During Saccadic Choice.

Recent work in decision neuroscience suggests that visual saliency can interact with reward-based choice, and the lateral intraparietal cortex (LIP) is implicated in this process. In this study, we recorded from LIP neurons while monkeys performed a two alternative choice task in which the reward and luminance associated with each offer were varied independently. We discovered that the animal's choice was dictated by the reward amount while the luminance had a marginal effect. In the LIP, neuronal activity corresponded well with the animal's choice pattern, in that a majority of reward-modulated neurons encoded the reward amount in the neuron's preferred hemifield with a positive slope. In contrast, compared to their responses to low luminance, an approximately equal proportion of luminance-sensitive neurons responded to high luminance with increased or decreased activity, leading to a much weaker population-level response. Meanwhile, in the non-preferred hemifield, the strength of encoding for reward amount and luminance was positively correlated, suggesting the integration of these two factors in the LIP. Moreover, neurons encoding reward and luminance were homogeneously distributed along the anterior-posterior axis of the LIP. Overall, our study provides further evidence supporting the neural instantiation of a priority map in the LIP in reward-based decisions.