Challenges and perspectives in computational deconvolution of genomics data.

Deciphering cell-type heterogeneity is crucial for systematically understanding tissue homeostasis and its dysregulation in diseases. Computational deconvolution is an efficient approach for estimating cell-type abundances from a variety of omics data. Despite substantial methodological progress in computational deconvolution in recent years, challenges are still outstanding. Here we enlist four important challenges related to computational deconvolution: the quality of the reference data, generation of ground truth data, limitations of computational methodologies, and benchmarking design and implementation. Finally, we make recommendations on reference data generation, new directions of computational methodologies, and strategies to promote rigorous benchmarking.

Effects of computerized working memory training on neuroplasticity in healthy individuals: A combined neuroimaging and neurotransmitter study.

Working memory (WM) is an essential cognitive function that underpins various higher-order cognitive processes. Improving WM capacity through targeted training interventions has emergered as a potential approach for enhancing cognitive abilities. The present study employed an 8-week regimen of computerized WM training (WMT) to investigate its effect on neuroplasticity in healthy individuals, utilizing neuroimaging data gathered both before and after the training. The key metrics assessed included the amplitude of low-frequency fluctuations (ALFF), voxel-based morphometry (VBM), and the spatial distribution correlations of neurotransmitter. The results indicated that post-training, compared to baseline, there was a reduction in ALFF in the medial superior frontal gyrus and an elevation in ALFF in the left middle occipital gyrus within the training group. In comparison to the control group, the training group also exhibited decreased ALFF in the anterior cingulate cortex, angular gyrus, and superior parietal lobule, along with increased ALFF in the postcentral gyrus post-training. VBM analysis revealed a significant increase in gray matter volume (GMV) in the right dorsal superior frontal gyrus after the training period, compared to the initial baseline measurement. Furthermore, the training group showed GMV increases in the dorsal superior frontal gyrus, Rolandic operculum, precentral gyrus, and postcentral gyrus when compared to the control group. In addition, significant associations were identifed between neuroimaging measurements (AFLL and VBM) and the spatial patterns of neurotransmitters such as serotonin (5-HT), dopamine (DA), and N-methyl-D-aspartate (NMDA), providing insights into the underlying neurochemical processes. These findings clarify the neuroplastic changes caused by WMT, offering a deeper understanding of brain plasticity and highlighting the potential advantages of cognitive training interventions.

Textural Precursor Compositions Harvested for Independent Signal Generators: Scaling Micron-Sized Flower-Like Metal-Organic Frameworks as Amplifying Units for Dual-Mode Glycoprotein Assay.

In this work, a micron-sized flower-like metal-organic frameworks (MOFs)-based boronate-affinity sandwich-type immunoassay was fabricated for the dual-mode glycoprotein assay. For proof of concept, the flower-like MOFs were synthesized from transition Cu nodes and tetrakis (4-carboxyphenyl) porphyrin (TCPP) ligands by spontaneous standing assembly. In addition, the specificity toward glycoprotein involved the antigen recognition as well as covalent bonding via the boronate-glycan affinity, and the immediate signal responses were initiated by textural decomposition of the flower-like MOFs. Intriguingly, Cu nodes, of which the valence state is dominant by CuI species, can endow the Fenton-like catalytic reaction of the fluorogenic substrate for generating fluorescence signals. For benefits, TCPP ligands, in which each TCPP molecule has four guest donors, can provide multiple valences for the assembly of cyclodextrin-capped gold nanoparticles via host-guest interaction for colorimetry output. Albeit important, the scaling micrometer patterns for the flower-like MOFs carrying numerous Cu nodes and TCPP ligands can also function as amplifying units, signifying the output signal. The detection limit of the dual-mode glycoprotein assay can reach 10.5 nM for the fluorescence mode and 18.7 nM for the colorimetry mode, respectively. Furthermore, the merits of harvesting different signal generators toward the multimodal readout patterns can allow the mutual verification and make the analytical results more reliable. Collectively, our proposed assay may offer a new idea in combining the inherent textural merits from MOFs for dual signal generators, which can also emphasize accurate detection capability for glycoprotein assay.

Predictive factors that influence the clinical efficacy of umbilical cord-derived mesenchymal stromal cells in the treatment of type 2 diabetes mellitus.

BACKGROUND: Our previous single-center, randomized, double-blinded, placebo-controlled phase 2 study evaluated the safety and effectiveness of human umbilical cord mesenchymal stromal cell (UC-MSC) transfusion for treating patients with type 2 diabetes mellitus (T2DM). Indeed, this potential treatment strategy was able to reduce insulin use by half in a considerable number of patients. However, many other patients' responses to UC-MSC transfusion were insignificant. The selection of patients who might benefit from UC-MSC treatment is crucial from a clinical standpoint. METHODS: In this post hoc analysis, 37 patients who received UC-MSC transfusions were divided into two groups based on whether their glycated hemoglobin (hemoglobin A1c, or HbA1c) level was less than 7% after receiving UC-MSC treatment. The baseline differences between the two groups were summarized, and potential factors influencing efficacy of UC-MSCs for T2DM were analyzed by univariate and multivariate logistic regression. The correlations between the relevant hormone levels and the treatment effect were further analyzed. RESULTS: At the 9-week follow-up, 59.5% of patients achieved their targeted HbA1c level. Male patients with lower baseline HbA1c and greater C-peptide area under the curve (AUCC-pep) values responded favorably to UC-MSC transfusion, according to multivariate analysis. The effectiveness of UC-MSCs transfusion was predicted by AUCC-pep (cutoff value: 14.22 ng/h/mL). Further investigation revealed that AUCC-pep was increased in male patients with greater baseline testosterone levels. CONCLUSIONS: Male patients with T2DM with greater AUCC-pep may be more likely to respond clinically to UC-MSC therapy, and further large-scale multi-ethnic clinical studies should be performed to confirm the conclusion.

Efficacy of noiiglutide injection on body weight in obese Chinese adults without diabetes: A multicentre, randomized, double-blind, placebo-controlled, phase 2 trial.

AIM: To evaluate the effect of noiiglutide as an adjunct to lifestyle intervention on the reduction in body weight and tolerability in obese Chinese adults without diabetes. MATERIALS AND METHODS: In this 24-week, randomized, double-blind, placebo-controlled phase 2 trial, 254 obese adults with a body mass index of 28.0-40.0 kg/m2 and without diabetes were enrolled. Participants were initially randomized in a 1:1:1 ratio to one of three dose levels: 0.12, 0.24, or 0.36 mg of the study treatment. Within each dose level, participants were further randomized in a 3:1 ratio to receive either subcutaneous injection of noiiglutide or a matching placebo. The primary endpoint was the change in body weight from baseline to week 24. RESULTS: Across all noiiglutide dosage levels, least squares mean reductions in body weight from baseline to week 24 ranged from 8.03 to 8.50 kg, compared with 3.65 kg in the placebo group (all p-values <.0001). In the noiiglutide groups (0.12, 0.24, 0.36 mg/day), a significantly higher proportion of participants achieved a weight loss ≥5% (68.8%, 60.0%, 73.0%) and ≥10% (37.5%, 36.9%, 39.7%), compared with the pooled placebo group (≥5%: 29.0%; ≥10%: 8.1%). Gastrointestinal adverse events, such as nausea, diarrhoea and vomiting, were more common in all noiiglutide groups (15.4%-30.2%, 18.8%-22.2%, 15.6%-18.5%) than in the pooled placebo group (8.1%, 6.5%, 0%). CONCLUSIONS: In obese Chinese adults without diabetes, once-daily subcutaneous noiiglutide significantly reduced body week at week 24 compared with placebo, and had a manageable safety profile, primarily involving gastrointestinal disorders.

Associations between cord blood acetaminophen biomarkers and childhood asthma with and without allergic comorbidities.

BACKGROUND: Previous studies have linked prenatal acetaminophen use to increased asthma risk in children. However, none have explored this association while differentiating between asthma cases with and without other allergic conditions or by employing objective biomarkers to assess acetaminophen exposure. OBJECTIVE: To evaluate whether the detection of acetaminophen biomarkers in cord blood is associated with the subgroups of asthma both with and without allergic comorbidities in children. METHODS: Acetaminophen biomarkers, including unchanged acetaminophen and acetaminophen glucuronide, were measured in neonatal cord blood samples from the Boston Birth Cohort. Asthma subgroups were defined on the basis of physician diagnoses of asthma and other allergic conditions (atopic dermatitis and allergic rhinitis). Multinomial regressions were used to evaluate the associations between acetaminophen biomarkers and asthma subgroups, adjusting for multiple confounders, including potential indications for maternal acetaminophen use such as maternal fever. RESULTS: The study included 142 children with asthma and at least 1 other allergic condition, 55 children with asthma but no other allergic condition, and 613 children free of asthma. Detection of acetaminophen in cord blood, reflecting maternal exposure to acetaminophen shortly before delivery, was associated with 3.73 times the odds of developing asthma without allergic comorbidities (95% CI: 1.79-7.80, P = .0004). In contrast, the detection of acetaminophen in cord blood was not associated with an elevated risk of asthma with allergic comorbidities. Analysis of acetaminophen glucuronide yielded consistent results. CONCLUSION: In a prospective birth cohort, cord blood acetaminophen biomarkers were associated with an increased risk of childhood asthma without allergic comorbidities, but were not associated with childhood asthma with allergic comorbidities.

The evaluation value of atherogenic index of plasma and high-sensitivity C-reactive protein for the degree of coronary artery lesion in premature coronary artery disease.

BACKGROUND: Premature coronary artery disease (PCAD) is prevailing. We aimed to investigate the evaluation value of atherogenic index of plasma (AIP) and high-sensitivity C-reactive protein (hs-CRP) for the occurrence and severity of coronary artery lesion in PCAD patients. METHODS: PCAD (PACD group)/non-PCAD (control group) patients were enrolled. The coronary artery lesion degree was evaluated using Gensini score (GS). PCAD patients were allocated into the low/medium/high GS groups, with general clinical baseline data analyzed. Plasma hs-CRP/AIP levels were compared in PCAD patients with different disease degree. Correlations between plasma hs-CRP/AIP with Gensini score, independent risk factors affecting the occurrence of PCAD, and the predictive value of hs-CRP/AIP/their combination for the occurrence and degree of PCAD were evaluated by Spearman correlation analysis/Logistic multivariate regression/receiver operating characteristic (ROC) curve. The differences in the area under the curve (AUC) were compared using MedCalc-Comparison of ROC curves. RESULTS: Plasma hs-CRP/AIP levels in the PCAD group were increased. Plasma hs-CRP/AIP levels varied significantly among PCAD patients with different disease degree. Plasma hs-CRP/AIP levels were markedly positively correlated with the Gensini score. Smoking history/homocysteine/fasting blood-glucose/hs-CRP/AIP were all independent risk factors affecting PCAD occurrence. The AUC of hs-CRP and AIP combination predicting the occurrence of PCAD was 0.950 (90.80% sensitivity/93.33% specificity). hs-CRP/AIP combination assisted in predicting the disease degree in PCAD patients. CONCLUSIONS: AIP and hs-CRP are independent risk factors for the occurrence of PCAD, and their combination has high predictive value for PCAD occurrence and disease degree, which are both positively correlated with coronary artery lesion degree.

Associations between perceived and actual risk of HIV infection and HIV prevention services uptake among men who have sex with men in Shandong province, China: a cross-sectional study.

BACKGROUND: Associations between perceived and actual risk of HIV infection and HIV prevention services uptake are inconclusive. This study aimed to evaluate the discrepancy between the perceived and actual HIV risk, and quantify the associations between perceived and actual risk of HIV infection and three HIV prevention services utilization among men who have sex with men (MSM) in Shandong province, China. METHODS: A cross-sectional study was conducted in Shandong province in June 2021. Participants were eligible if they were born biologically male, aged 18 years or older, had negative or unknown HIV status, and had sex with men in the past year. Participants were recruited online. The discrepancy between their perceived and actual risk of HIV infection was evaluated by calculating the Kappa value. Bayesian model averaging was used to assess the associations between perceived and actual risk of HIV infection and HIV prevention services uptake. RESULTS: A total of 1136 MSM were recruited, most of them were 30 years old or younger (59.9%), single (79.5%), with at least college education level (74.7%). Most participants (97.4%) perceived that they had low risk of HIV infection, and 14.1% were assessed with high actual risk. The discrepancy between their perceived and actual risk of HIV infection was evaluated with a Kappa value of 0.076 (P < 0.001). HIV testing uptake had a weak association with perceived high HIV prevalence among social networks (aOR = 1.156, post probability = 0.547). The perceived high HIV prevalence among national MSM was positive related to willingness to use PrEP (aOR = 1.903, post probability = 0.943) and PEP (aOR = 1.737, post probability = 0.829). Perceived personal risk (aOR = 4.486, post probability = 0.994) and perceived HIV prevalence among social networks (aOR = 1.280, post probability = 0.572) were related to history of using PrEP. Perceived personal risk (aOR = 3.144, post probability = 0.952), actual risk (aOR = 1.890, post probability = 0.950), and perceived risk among social networks (aOR = 1.502, post probability = 0.786) were related to history of using PEP. CONCLUSIONS: There is discordance between perceived and actual personal risk of HIV infection among MSM in China. HIV risk assessment and education on HIV prevalence among MSM should be strengthened to assist high-risk populations aware their risk accurately and hence access HIV prevention services proactively.

Mapping the evolving trend of research on Class III malocclusion: a bibliometric analysis.

OBJECTIVES: This study aimed to provide visualized knowledge maps to show the evolving trends and key focal points of Class III malocclusion research through a comprehensive bibliometric analysis. MATERIALS AND METHODS: Class III malocclusion research published between 2000 and 2023 was retrieved from the Web of Science Core Collection. VOSviewer was utilized to count the citation and publication number of authors, institutions, countries and journals. Co-occurrence, co-citation, and cluster analyses and burst detection were conducted using CiteSpace. RESULTS: A total of 3,682 publications on Class III malocclusion were included in the bibliometric analysis. During 2000-2023, both the annual publication count and citation frequency exhibited a gradual upward trajectory, with a noticeable surge in recent years. In terms of production and citation counts of Class III malocclusion research, the core journal is the American Journal of Orthodontics and Dentofacial Orthopedics. Furthermore, apart from the primary keyword 'Class III malocclusion', 'orthognathic surgery' was identified as keyword with the most frequency. The cluster analysis of cited references reveals that the research focal points have shifted to 'skeletal anchorage' and 'surgery-first approach'. Furthermore, the burst detection identified 'quality of life' as a potential research hotspot since it has recently gained increasing scholarly attention. CONCLUSIONS: The current study provides scholars with the knowledge maps of evolving trends and prominent topics of Class III malocclusion research and a summary of research progress on various priorities during different periods. These findings are expected to provide a valuable guidance to facilitate the future research on Class III malocclusion.

Temporomandibular disorder patients with excessive daytime sleepiness present greater pain intensity and reduced jaw function.

BACKGROUND: Sleep disorders are associated with temporomandibular disorders (TMDs). Limited studies have focused on excessive daytime sleepiness (EDS) and its impact on jaw functions in TMD patients. OBJECTIVE: The aim of the present investigation was to identify the impact of EDS on pain and jaw function in TMD patients. METHODS: A total of 338 TMD patients (50 males and 288 females) was included. The Epworth Sleepiness Scale (ESS) was used to classify patients into EDS group (score ≥ 10) and non-EDS group (score < 10). The Jaw Functional Limitation Scale 8-item (JFLS-8) was used to assess the severity of jaw dysfunction. Pain intensity was evaluated using the Visual Analogue Scale (VAS). Anxiety and depression were evaluated using the Generalised Anxiety Disorder 7-item (GAD-7) and the Patient Health Questionnaire 9-item (PHQ-9). All included patients were diagnosed with pain-related TMD (PT), intra-articular TMD (IT) or combined TMD (CT). RESULTS: Compared with non-EDS patients, EDS patients exhibited more severe jaw dysfunction, greater pain intensity and higher PHQ-9 scores (p < .05). Multivariate analyses showed that EDS (B = 3.69), female gender (B = 3.69), and elevated GAD-7 score (B = 0.73) were significantly associated with an increased score on the JFLS-8 (p < .05). Moreover, bivariate logistic regression analysis indicated a significant relationship between EDS and PT (OR = 2.70, p = .007). CONCLUSION: The presence of EDS was more closely related to PT, but the causal relationship between them needs to be further confirmed. More concern and intervention to alleviate poor sleep quality might be highlighted during the treatment of TMD, especially PT subtype.

Virtual Reality Mental Health Interventions in Geriatric Care for Functional or Well-being Enhancement - A Scoping Review.

PURPOSE: It has become common to use Virtual Reality (VR) for mental health interventions; however, its use in care of the elederly is limited, especially regarding mood and well-being. In this review, we summarize the results of current VR-based mental health interventions for this population. METHODS: Peer-reviewed journal articles on immersive VR mental health intervention in seniors, published until 2022, were included. RESULTS: There were 2697 results found in the database search, of which 40 articles met the inclusion criteria and were included in the final analysis. Most studies did not use an experimental design with randomized controlled trials and follow-up sessions. Function-oriented and entertainment-oriented intervention studies were categorized. VR-based geriatric mental interventions have grown rapidly since 2018, especially the number of interventions that promote wellbeing. The function-oriented interventions used active interactions with varied devices. Entertainment-oriented interaction was primarily passive, seldomly using hand controllers for moving activities. Generally, VR interventions improved the mental health of older adults. CONCLUSION: Geriatric rehabilitation can benefit from this innovative technology to maintain cognitive functions and to improve the well-being of seniors. They have potential for use in aging care and in retirement homes. Future VR interventions may also involve promoting social interaction to combat loneliness among seniors.

Knowledge on cause, clinical manifestation and treatment for fibromyalgia among medical doctors: A worldwide survey.

OBJECTIVES: Hench introduced the fibromyalgia syndrome almost 50 years ago. In the meantime, the prevalence has increased, the clinical criteria have changed and the way we explain (chronic) pain has altered. DESIGN: In the current study, we conducted a worldwide survey in which we investigate whether medical doctors are familiar with the American College of Rheumatology (ACR) criteria for fibromyalgia and, if so, whether these medical doctors adhere to the clinical guidelines following evidence-based treatments. RESULTS: In total, 286 medical doctors from 43 countries spread over 6 continents filled out the survey. In most of the countries, the diagnosis fibromyalgia was used. Only 10% adhere to the ACR criteria, widespread pain (44%), unrefreshed sleep (24%), fatigue (20%) and cognitive problems (8%) were most used diagnostic criteria. Of the respondents, 94 (32%) mentioned that the cause is unknown or idiopathic, but also a wide variety of other causes was mentioned. More than 70 different treatment options were provided, of which 24% of the responses were classified as according to the clinical guidelines. From this study, we conclude that many medical doctors do not follow the ACR criteria; the majority has an inappropriate knowledge of causes for fibromyalgia and that a minority of treatment advice adhere to the guidelines.

Impact of Virtual Reality-Based Group Activities on Activity Level and Well-Being Among Older Adults in Nursing Homes: Longitudinal Exploratory Study.

BACKGROUND: In addition to illness, inactivity is a risk factor for high mortality in nursing homes. Using innovative technology, such as virtual reality (VR), for meaningful group activities could provide new opportunities for solving this problem. VR interventions have already been approved as a promising method for enhancing the health of older adults. OBJECTIVE: In this study, we examined whether VR-based group activities can have a positive impact on activity level and group interaction among older adults living in nursing homes. METHODS: We conducted a longitudinal study and provided VR interventions as a group activity once a week for 4 consecutive weeks in nursing homes. Participants were recruited based on the experience of the nursing staff members and the natural decisions of the older adults. Within a virtual cottage, designed according to the needs of the target group, older adults were able to perform daily tasks that they were no longer able to do in real life, such as gardening and making pizza. Overall, 2 psychologists measured the psychosocial capacities, activities of daily life, and well-being before and after the interventions using standardized instruments. RESULTS: The results focus on a total of 84 older adults from 14 nursing homes who completed at least 3 VR interventions. The results indicate that several psychosocial capacities among the older adults improved, including adherence to regulations (P<.001; η²=0.122), flexibility (P<.001; η²=0.109), and group integration (P<.001; η²=0.141). Problems related to competence also showed a slight decrease (P=.04; η²=0.039). In addition, the VR intervention promoted their proactivity (P<.001; η²=0.104) and mobility (P=.04; η²=0.039). During the VR group intervention, older adults' well-being could be maintained at a high level. The results highlight the beneficial effects of VR intervention as a meaningful activity in nursing homes, showcasing the potential of VR applications in this setting. CONCLUSIONS: This study provides a novel and naturalistic perspective, offering new insights into the use of VR in nursing homes. The VR intervention was well accepted and fulfilled the aim of enhancing capacity and well-being. It could be a meaningful group activity in nursing homes to improve social group interaction. To provide stronger evidence, randomized controlled trials are necessary.

Nanomaterial-based drug-delivery system as an aid to antimicrobial photodynamic therapy in treating oral biofilm.

Diverse microorganisms live as biofilm in the mouth accounts for oral diseases and treatment failure. For decades, the prevention and treatment of oral biofilm is a global challenge. Antimicrobial photodynamic therapy (aPDT) holds promise for oral biofilm elimination due to its several traits, including broad-spectrum antimicrobial capacity, lower possibility of resistance and low cytotoxicity. However, the physicochemical properties of photosensitizers and the biological barrier of oral biofilm have limited the efficiency of aPDT. Nanomaterials has been used to fabricate nanocarriers to improve photosensitizer properties and thus enhance antimicrobial effect. In this review, we have discussed the challenges of aPDT used in dentistry, categorized the nanomaterial-delivery system and listed the possible mechanisms involved in nanomaterials when enhancing aPDT effect.

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Investigating the molecular mechanisms underlying the co-occurrence of Parkinson's disease and inflammatory bowel disease through the integration of multiple datasets.

Parkinson's disease (PD) and inflammatory bowel disease (IBD) are chronic diseases affecting the central nervous system and gastrointestinal tract, respectively. Recent research suggests a bidirectional relationship between neurodegeneration in PD and intestinal inflammation in IBD. PD patients may experience gastrointestinal dysfunction over a decade before motor symptom onset, and IBD may increase the risk of developing PD. Despite the "gut-brain axis" concept, the underlying pathophysiological mechanisms of this potential association remain unclear. This study aimed to investigate the biological mechanisms of differentially expressed genes in PD and IBD using bioinformatics tools, providing novel insights into the co-diagnosis and treatment of these diseases. We constructed a gene marker for disease diagnosis and identified five important genes (BTK, NCF2, CRH, FCGR3A and SERPINA3). Through nomogram and decision tree analyses, we found that both the IBD and PD required only the expression levels of BTK and NCF2 for accurate discrimination. Additionally, small molecule drugs RO-90-7501 and MST-312 may be useful for the treatment of both IBD and PD. These findings offer new perspectives on the co-diagnosis and treatment of PD and IBD, and suggest that targeting BTK may be a promising therapeutic strategy for both diseases.

Nanoarchitectonics-Based Materials as a Promising Strategy in the Treatment of Endodontic Infections.

Endodontic infections arise from the interactive activities of microbial communities colonizing in the intricate root canal system. The present study aims to update the latest knowledge of nanomaterials, their antimicrobial mechanisms, and their applications in endodontics. A detailed literature review of the current knowledge of nanomaterials used in endodontic applications was performed using the PubMed database. Antimicrobial nanomaterials with a small size, large specific surface area, and high chemical activity are introduced to act as irrigants, photosensitizer delivery systems, and medicaments, or to modify sealers. The application of nanomaterials in the endodontic field could enhance antimicrobial efficiency, increase dentin tubule penetration, and improve treatment outcomes. This study supports the potential of nanomaterials as a promising strategy in treating endodontic infections.

Effect of High-Temperature Deformation Twinning on the Work Hardening Behavior of Fe-38Mn Alloy during Hot Shear-Compression Deformation.

The effect of high-temperature deformation twinning on the work hardening behaviors of Fe-38Mn alloy during hot shear-compression deformation was investigated. The discovery of micro-shear bands and deformation twinning is significant for continuous work hardening, and this represents an important step toward gaining a complete understanding of the effect of deformation twinning on work hardening behaviors. Deformation twinning is widely acknowledged to accommodate plastic strain under cold deformation, even under severe plastic deformation. At present, the equivalent stress vs. strain curves for hot shear-compression deformation of Fe-38Mn alloy exhibit the characteristics of continuous work hardening. In addition, continuous work hardening is classified into five stages when considering high-temperature deformation twinning.

The LiaSR Two-Component System Regulates Resistance to Chlorhexidine in Streptococcus mutans.

Chlorhexidine (CHX) is widely considered to be the gold standard for preventing dental caries. However, it is possible to induce resistance to CHX. The LiaSR two-component system has been identified that contributed to CHX resistance in Streptococcus mutans, which is one of the major pathogens in dental caries. However, the underlying mechanisms remain unclear. In this study, an MIC assay and a viability assessment demonstrated that after deleting the liaS and liaR genes, the sensitivity of mutants could increase. The Nile Red efflux assay exhibited that the efflux rates of mutants were significantly decreased. The RT-qPCR results indicated that the LiaSR two-component system-mediating influence on the expression of lmrB in S. mutans contributed to the efflux rate. The hydrophobicity assay and membrane potential assay showed that the mutants had higher levels of hydrophobicity and depolarization, suggesting that their membranes were more easily disturbed. The TEM graphs revealed that the border of the cell membrane was unclear in mutants compared with the wild-type strain, indicating that the cell envelope's stress response may have been inhibited. While the surface charge of mutants showed no significant difference in the wild-type strain according to the result of cytochrome c-based charged determination. This study provides valuable novel insights into the mechanisms of the LiaSR two-component system in the CHX resistance of S. mutans.

Hexabromocyclododecane-induced reproductive toxicity in Brachionus plicatilis: Impacts and assessment.

Hexabromocyclododecane (HBCD), third-generation brominated flame retardants (BRFs), has aroused worldwide concern because of its wide application and potentially negative impacts on marine ecosystems, but an information gap still exists regarding marine low-trophic organisms. Brachionus plicatilis, the model marine zooplankton, was used in the present study, and its reproductive responses were used as the endpoint to indicate HBCD-induced toxicity. HBCD was suggested to be extremely highly toxic compounds regarding the 96 h-LC50 of 0.58 mg L-1. The sublethal exposure of HBCD injured the reproduction of B. plicatilis: The total number of offspring per female and the key population index calculated from the life table, including the intrinsic rate of population increase (rm) and net reproductive rate (R0), were significantly influenced in a concentration-dependent manner. The reproductive process was also altered, as indicated by the first spawning time, first hatching time and oocyst development time. At the same time, individual survival and growth (body length) were also negatively affected by HBCD. Reactive oxygen species (ROS) were suggested to be responsible for reproductive toxicity mainly because the total ROS contents as well as the main components of •OH and H2O2 greatly increased and resulted in the oxidative imbalance that presented as malondialdehyde (MDA) elevation. Simultaneous activation of the glutathione antioxidant system was accompanied by the apoptosis marker enzymes Caspase-3 and 9, as well as the correlation between ROS content, physiological alteration and cell apoptosis, providing further evidence for this. The integrated biomarker response (IBR) and adverse outcome pathway (AOP) showed that HBCD had a significant toxic effect on B. plicatilis near the concentration range of 96 h-LC50. The establishment of this concentration range will provide a reliable reference for future environmental concentration warning of HBCD in marine.

A self-calibrating ratiometric fluorescence sensor with photonic crystal-based signal amplification for the detection of tetracycline in food.

A dual-color ratiometric fluorescence sensor based on photonic crystals (PCs) was developed to detect tetracycline (TC) in food. PC was fabricated via self-assembly of carbon dots (CDs)-loaded SiO2 nanoparticles. Gold nanoclusters (AuNCs) and copper ions (Cu2+) were then adsorbed onto the PC for sensor fabrication. The fluorescence of AuNCs was amplified by the PC with an enhancement ratio of 7.6, providing higher sensitivity. The fluorescence of AuNCs was quenched by Cu2+, whereas that of CDs remained unchanged as an internal reference. TC restored the fluorescence of AuNCs owing to its complexation with Cu2+, resulting in a change in the fluorescence intensity ratio. The sensor exhibited a good linear relationship with TC concentrations ranging from 0.1 to 10 µM, with a detection limit of 34 nM. Furthermore, the sensor was applied for TC detection in food with satisfactory recoveries and relative standard deviations, revealing great potential in practical application.