Single Living Cell "Observation-Analysis" Integrated Platform Decodes Cell Migration Plasticity Orchestrated by Nucleocytoplasmic STAT3.

Cell migration requires the interplay among diverse migration patterns. The molecular basis of distinct migration programs is undoubtedly vital but not fully explored. Meanwhile, the lack of tools for investigating spontaneous migratory plasticity in a single living cell also adds to the hindrance. Here, we developed a micro/nanotechnology-enabled single-cell analytical platform to achieve coherent monitoring of spontaneous migratory pattern and signaling molecules. Via the platform, we unveiled a previously unappreciated STAT3 regionalization on the multifunctional regulations of migration. Specifically, nuclear STAT3 is associated with amoeboid migration, while cytoplasmic STAT3 promotes mesenchymal movement. Opposing effects of JAK2 multisite phosphorylation shape its response to STAT3 distribution in a dynamic and antagonistic manner, eventually triggering a reversible amoeboid-mesenchymal transition. Based on the above results, bioinformatics further revealed a possible downstream regulator of nucleocytoplasmic STAT3. Thus, our platform, as an exciting technological advance in single-cell migration research, can provide in-depth mechanism interpretations of tumor metastasis and progression.

Effect of the ethnic, profession, gender, and social background on the perception of upper dental midline deviations in smile esthetics by Chinese and Black raters.

BACKGROUND: The purpose of this study was to compare the perception of upper dental midline deviation on the attractiveness of a smile among raters from different ethnicities, professions, genders, and ages and measure to what extent the presence or absence of the associated smiling structures influence the raters' evaluations. METHODS: A male subject (26 years of age) with adequate smile characteristics was selected by 3 experienced orthodontists, and 561 raters from 2 different ethnic groups (281 Chinese raters and 280 Black raters) rated the subject's smile after the subject's upper dental midline was digitally altered from 0 to 5 mm using a 5-point Likert scale on 12 smile photographs divided into two groups: group 1, in the presence of smile related structures, two-thirds of the nose, lips, and chin (NLC), and group 2, in the absence of smile related structures, the lips only (L). RESULTS: There were statistically significant differences (p < 0.05) between the two ethnicities, in 2 mm and 4 mm in-group NLC and 5 mm in-group L, as well as the raters' profession to each midline shift of both groups (NLC) and (L) for both ethnicities except for 0 mm. Regarding the role of associated smile structures, the smile photos were observed in the presence of smile-associated structures, and in its absence (NLC × L), statistically significant differences (p < 0.05) were found when the deviation was 5 mm among the Chinese raters; in 1 mm, and 4 mm among the Black raters. Among different genders, statistical differences were only reported (p < 0.05) for Chinese raters for 5 mm in NLC, while statistical differences were observed for 2 mm and 3 mm in NLC for Black raters. For age categories, differences were observed (p < 0.05) for 4 mm, 5 mm in NLC and 4 mm, and 5 mm in L for Chinese raters, while 5 mm in NLC and 1 mm in L for Black raters. CONCLUSION: Perception of the upper dental midline deviations was influenced by the factors of ethnicity, profession, presence or absence of smile-associated structures, as well as the gender and age of the raters.

Impaired vessel relaxation response and increased infarct size in smooth muscle cannabinoid receptor 1 knockout mice.

Cannabinoids are reported to regulate cardiovascular functions. Cannabinoid receptors 1 (CB1Rs) are widely expressed in both the neuronal system and vascular system, but the contribution of CB1Rs in vascular smooth muscle (CB1RSM) to cardiovascular functions is not clear yet. In this research, we analyzed the effects of CB1RSM on blood pressure, vasoconstriction, and vasodilation abilities by using conditionally CB1R knockout mice (CB1RSMKO). The results show no significant difference in basal blood pressure between the conscious CB1RSMKO and control mice, indicating that CB1RSM is not essential for basal blood pressure maintenance. The constriction of the CB1RSMKO mesenteric artery in vitro was not significantly altered compared with that of the control mice. In contrast, the relaxation to CB1R agonist 2-AG or WIN55212-2 was decreased in CB1RSMKO vessels, suggesting that activation of CB1RSM mediates the vasodilation effect of cannabinoids. Ischemia stroke mouse model was used to further identify the potential function of CB1RSM in pathological conditions, and the results showed that the infarct volume in CB1RSMKO mice is significantly increased compared with the control littermates. These results suggest that vascular CB1R may not play a central role in basal vascular health maintenance but is protective in ischemia states, such as stroke. The protection function may be mediated, at least partly, by the relaxation effect of CB1RSM-dependent activities of endocannabinoids.

Motivational Interviewing on Periodontal Treatment Outcomes: A Meta-Analysis.

OBJECTIVES: This systematic review investigated the clinical efficacy of motivational interviewing (MI) in improving oral hygiene and periodontal health in patients with periodontal diseases. METHODS: A comprehensive literature search was conducted across various databases up to May 2023. Randomised controlled trials (RCTs) evaluating the effects of MI on periodontal conditions in patients with gingivitis, periodontitis, and peri­implantitis were included. After data screening, a risk-of-bias assessment was performed using the Cochrane risk of bias (RoB) tool. The meta-analysis was performed using random-effects models. RESULTS: Out of 2108 records screened, 7 RCTs involving 474 patients were included in the qualitative synthesis, with 6 of these studies included in the meta-analysis. Amongst these, 5 studies had a high RoB and 2 had some concerns about bias. Although individual studies reported varied results regarding the effects of MI on different periodontal indices and parameters at different time points, the pooled results revealed no significant difference in the overall effect on plaque level, bleeding on probing, and gingival inflammation between the MI and control groups. In addition, there is insufficient evidence to suggest any significant effect on attachment loss or probing depth. CONCLUSIONS: The current evidence is insufficient to support the effectiveness of MI as an adjunctive intervention for improving oral hygiene and periodontal outcomes. However, these results should be interpreted with caution. Additional high-quality studies with standardised MI interventions are required to derive definite conclusions.

Chemo-Selective Single-Cell Metabolomics Reveals the Spatiotemporal Behavior of Exogenous Pollutants During Xenopus Laevis Embryogenesis.

In-depth profiling of embryogenesis-associated endogenous and exogenous metabolic changes can reveal potential bio-effects resulting from human-made chemicals and underlying mechanisms. Due to the lack of potent tools for monitoring spatiotemporal distribution and bio-transformation behavior of dynamic metabolites at single-cell resolution, however, how and to what extent environmental chemicals may influence or interfere embryogenesis largely remain unclear. Herein, a zero-sample-loss micro-biopsy-based mass spectrometric platform is presented for quantitative, chemo-selective, high-coverage, and minimal-destructive profiling of development-associated cis-diol metabolites, which are critical for signal transduction and epigenome regulation, at both cellular level and tissue level of Xenopus laevis. Using this platform, three extraordinary findings that are otherwise hard to achieve are revealed: 1) there are characteristically different cis-diol metabolic signatures among oocytes, anterior and posterior part of tailbud-stage embryos; 2) halogenated cis-diols heavily accumulate at the posterior part of tailbud-stage embryos of Xenopus laevis; 3) dimethachlon, a kind of exogenous fungicide that is widely used as pesticide, may be bio-transformed and accumulated in vertebrate animals in environment. Thus, this study opens a new avenue to simultaneously monitoring intercellular and intraembryonic heterogeneity of endogenous and exogenous metabolites, providing new insights into metabolic remolding during embryogenesis and putting a warning on potential environmental risk.

Understanding the experiences of patients with cancers in hospitals during COVID-19 pandemic in China: A qualitative research study.

AIM: To explore the experiences of patients with cancers in hospitals during the COVID-19 pandemic. DESIGN: A qualitative research study. METHODS: Using a phenomenological approach, we enrolled 22 patients with cancers in the Hunan Cancer Hospital from 20 February 2020 to 10 April 2020. The interviews were conducted face-to-face and were analysed by Colaizzi's 7-step method. This study aligns with the COREQ checklist. RESULTS: The experiences of patients with cancers in hospitals during the COVID-19 pandemic can be categorized into four major themes: (1) emotional changes; (2) delays in visiting hospital; (3) barriers to accessing medical care services, and (4) inconvenience related to logistics services.

Proton-Conductive 3D LnIII Metal-Organic Frameworks for Formic Acid Impedance Sensing.

Metal-organic frameworks (MOFs) as new classes of proton-conducting materials have been highlighted in recent years. Nevertheless, the exploration of proton-conducting MOFs as formic acid sensors is extremely lacking. Herein, we prepared two highly stable 3D isostructural lanthanide(III) MOFs, {(M(µ3 -HPhIDC)(µ2 -C2 O4 )0.5 (H2 O))⋅2 H2 O}n (M=Tb (ZZU-1); Eu (ZZU-2)) (H3 PhIDC=2-phenyl-1H-imidazole-4,5-dicarboxylic acid), in which the coordinated and uncoordinated water molecules and uncoordinated imidazole N atoms play decisive roles for the high-performance proton conduction and recognition ability for formic acid. Both ZZU-1 and ZZU-2 show temperature- and humidity-dependent proton-conducting characteristics with high conductivities of 8.95×10-4 and 4.63×10-4  S cm-1 at 98 % RH and 100 °C, respectively. Importantly, the impedance values of the two MOF-based sensors decrease upon exposure to formic acid vapor generated from formic aqueous solutions at 25 °C with good reproducibility. By comparing the changes of impedance values, we can indirectly determine the concentration of HCOOH in aqueous solution. The results showed that the lowest detectable concentrations of formic acid aqueous solutions are 1.2×10-2  mol L-1 by ZZU-1 and 2.0×10-2  mol L-1 by ZZU-2. Furthermore, the two sensors can distinguish formic acid vapor from interfering vapors including MeOH, N-hexane, benzene, toluene, EtOH, acetone, acetic acid and butane. Our research provides a new platform of proton-conductive MOFs-based sensors for detecting formic acid.

Microbiome-Metabolomics Analysis of the Impacts of Long-Term Dietary Advanced-Glycation-End-Product Consumption on C57BL/6 Mouse Fecal Microbiota and Metabolites.

Thermally processed diets are widely consumed, although advanced-glycation end products (AGEs) are unavoidably formed. AGEs, clusters of protein-cross-linking products, become less digestible because they impair intestinal peptidase proteolysis. We characterized the impacts of dietary AGEs on gut microbiota through a microbiome-to-metabolome association study. C57BL/6 mice were fed a heat-treated diet (high-AGE diet, H-AGE) or a standard AIN-93G diet (low-AGE diet, L-AGE) for 8 months. Fecal-microbiota composition was examined by 16S rDNA sequencing, and fecal-metabolome profile was evaluated by gas chromatography-tandem time-of-flight mass spectrometry (GC-TOF-MS). Reduced α-diversity and altered microbiota composition with elevated Helicobacter levels were found in the H-AGE group, and among the 57 perturbed metabolites, protein-fermentation products (i.e., p-cresol and putrescine) were increased. Major dysfunctional metabolic pathways were associated with carbohydrate and amino acid metabolism in two groups. Moreover, high correlations were found between fluctuant gut microbiota and metabolites. These findings might reveal the underlying mechanisms of the detrimental impacts of dietary AGEs on host health.

Dietary advanced glycation end products modify gut microbial composition and partially increase colon permeability in rats.

SCOPE: The adverse impacts of dietary advanced glycation end products (AGEs) on health are currently of interest. These compounds are inevitably formed during thermal food processing and make foods less digestible because of protein cross-linking. This study examined not only whether dietary AGEs alter cecal microbiota and their metabolites but also their effects on colon permeability. METHODS AND RESULTS: Sprague-Dawley rats were exposed to a high-AGEs diet (AGEs content was increased by heating food at 125°C/3 h) for 6, 12, or 18 weeks. Cecal microbiota was analyzed by 16S rDNA gene sequencing. Colon permeability was assessed through histopathology, immunohistochemistry and endotoxin testing. Microbial metabolites (e.g. ammonia and short-chain fatty acids (SCFAs)) were also measured. AGEs treatment reduced the diversity and richness of the microbiota, especially saccharolytic bacteria such as Ruminococcaceae and Alloprevotella, which can produce SCFAs, whereas some putatively harmful bacteria (Desulfovibrio and Bacteroides) were increased. Protein fermentation was enhanced, supported by elevated ammonia and branched-chain fatty acid levels (p < 0.05). Additionally, the colonocytes structure changed and the expression of tight junction proteins in colon were decreased. CONCLUSION: Dietary AGEs detrimentally modulate gut microbial ecology and may partially increase colon permeability, which can adversely impact host health.