Stannous fluoride forms aggregates between outer and inner membranes leading to membrane rupture of Porphyromonas gingivalis and Prevotella pallens.

Objective: Stannous has been shown to bind to free lipopolysaccharides, thus preventing them from binding to TLR receptors. This study was undertaken to determine the histomorphological mechanism of stannous binding to anaerobic bacteria. Methods: Two bacteria associated with gingivitis and advanced periodontal disease, Porphyromonas gingivalis (P. gingivalis) and Prevotella pallens (P. pallens), were cultured in 25-1,000 µM of stannous fluoride and stannous chloride for 48 h. The growth rate was estimated using absorbance OD600. Bacterial cells were then fixed and processed for transmission electron microscopy (TEM) analysis. Results: Stannous fluoride inhibited proliferation of both P. gingivalis and P. pallens in a dose-dependent manner. There was a statistically significant suppression of the growth curve starting at 100 µM for P. pallens (P = 0.050) and 200 µM for P. gingivalis (P = 0.039). TEM analysis revealed a thick layer of polysaccharides (19.8 nm) in P. gingivalis. The outer and inner membranes were clearly visible with low electron densities in both bacteria. Stannous diffused into bacterial membranes and formed precipitates in the areas spanning outer and inner membranes and below inner membranes. Precipitates varied in size ranging from 46.4 to 84.5 nm in length, and 18.4 to 35.9 nm in width. The membranes were disintegrated in the region where stannous formed precipitates. Cytosolic contents were leaked out, and in several cases, small vesicles were formed. Stannous precipitates were more abundant in numbers and larger in size in bacteria treated with high concentrations (100-300 µM) than in low concentrations (25-50 µM) of stannous fluoride. Furthermore, most of the bacteria were disintegrated in the groups treated with 100-300 µM stannous fluoride. At low concentrations (25 µM), stannous fluoride formed complexes primarily around outer membranes, to which lipopolysaccharides are anchored. Stannous chloride results showed similar trends, but it was less potent than stannous fluoride. Conclusion: Stannous fluoride can penetrate bacteria, bind to the constituents of the membrane and form precipitates between outer and inner membranes and beneath inner membranes. These large precipitates damaged the integrity of membranes and allowed cytosolic contents to be leaked out. Stannous complexes formed at the outer membranes, even at low concentrations (25 µM).

Put Yourself out There! A Strategy for Effective Self-Promotion in Academic Medicine.

Introduction: Trainees and faculty in academic medicine often struggle with self-promotion. Barriers may be more formidable for women and other groups underrepresented in medicine. Experience-based stories illustrating personal strengths are preferable when engaging in self-promotion activities. Methods: We developed a 90- to 120-minute workshop utilizing approaches such as iterative journaling and peer discussion to teach the development of problem-action-result (PAR) stories for self-promotion efforts in interviews and written applications to new positions. Participants provided Likert-scale (1 = strongly disagree, 5 = strongly agree) and free-response evaluations, which we analyzed for workshop strengths and areas for improvement. Results: We presented the workshop in person to 28 pediatric residents and subsequently to 22 residents, fellows, and faculty at an in-person national meeting. Sixty-one percent of the resident group and 100% of the national workshop group completed the evaluation. Both groups reported high satisfaction with the workshop's format (M = 4.7) and content (M = 4.7) and indicated intention to use the skills learned (M = 4.7). Strengths included the PAR format, interactivity, journaling, opportunity for reflection, and tips for interviewing and writing. Areas to improve included offering the workshop earlier in the academic year and providing more written examples of PAR stories. Discussion: This workshop used strategies of personal reflection, journaling, and peer feedback to help participants understand behavior-based recruiting practices and the PAR framework as a strategy for successful self-promotion. Learners can use these strategies to develop greater confidence and efficacy and to address barriers to effective self-promotion they encounter.

Design, Synthesis, Bioactivity, and Tentative Exploration of Action Mode for Benzyl Ester-Containing Derivatives.

The active splicing strategy has witnessed improvement in bioactivity and antifungal spectra in pesticide discovery. Herein, a series of simple-structured molecules (Y1-Y53) containing chloro-substituted benzyl esters were designed using the above strategy. The structure-activity relationship (SAR) analysis demonstrated that the fatty acid fragment-structured esters were more effective than those containing an aromatic acid moiety or naphthenic acid part. Compounds Y36 and Y41, which featured a thiazole-4-acid moiety and trifluoromethyl aliphatic acid part, respectively, exhibited excellent in vivo curative activity (89.4%, 100 mg/L Y36) and in vitro fungicidal activity (EC50 = 0.708 mg/L, Y41) against Botrytis cinerea. Determination of antifungal spectra and analysis of scanning electron microscopy (SEM), membrane permeability, cell peroxidation, ergosterol content, oxalic acid pathways, and enzymatic assays were performed separately here. Compound Y41 is cost effective due to its simple structure and shows promise as a disease control candidate. In addition, Y41 might act on a novel target through a new pathway that disrupts the cell membrane integrity by inducing cell peroxidation.

EPAC1 and 2 inhibit K+ currents via PLC/PKC and NOS/PKG pathways in rat ventricular cardiomyocytes.

The Exchange Protein directly Activated by cAMP (EPAC) has been implicated in cardiac pro-arrhythmic signalling pathways including spontaneous diastolic Ca2+ leak from sarcoplasmic reticulum and increased Action Potential Duration (APD) in isolated ventricular cardiomyocytes. The AP lengthening following acute EPAC activation is mainly due to a decrease of repolarizing steady state K+ current (IKSS) but the mechanisms involved remain unknown. This study aimed to assess the role of EPAC1 and 2 in the decrease of IKSS and to investigate the underlying signalling pathways. AP and K+ currents were recorded with the whole cell configuration of the patch-clamp technique in freshly isolated rat ventricular myocytes. EPAC1 and 2 were pharmacologically activated with 8-CPTAM (10 µmol/L) and inhibited with R-Ce3F4 and ESI-05, respectively. Inhibition of EPAC1 and EPAC2 significantly decreased the effect of 8-CPTAM on APD and IKSS showing that both EPAC isoforms are involved in these effects. Unexpectedly, CaMKII inhibition by AIP or KN-93, and Ca2+ chelation by intracellular BAPTA, did not impact the response to 8-CPTAM. However, inhibition of PLC/PKC and NOS/PKG pathways partially prevents the 8-CPTAM-dependent decrease of IKSS. Finally, the cumulative inhibition of PKC and PKG blocked the 8-CPTAM effect, suggesting that these two actors work along parallel pathways to regulate IKSS upon EPAC activation. On the basis of such findings, we propose that EPAC1 and 2 are involved in APD lengthening by inhibiting a K+ current via both PLC/PKC and NOS/PKG pathways. This may have pathological implications since EPAC is upregulated in diseases such as cardiac hypertrophy.

Any better? A follow-up content analysis of adolescent sexual and reproductive health inclusion in Global Financing Facility country planning documents.

BACKGROUND: The Global Financing Facility (GFF) supports national reproductive, maternal, newborn, child, adolescent health, and nutrition needs. Previous analysis examined how adolescent sexual and reproductive health was represented in GFF national planning documents for 11 GFF partner countries. OBJECTIVES: This paper furthers that analysis for 16 GFF partner countries as part of a Special Series. METHODS: Content analysis was conducted on publicly available GFF planning documents for Afghanistan, Burkina Faso, Cambodia, CAR, Côte d'Ivoire, Guinea, Haiti, Indonesia, Madagascar, Malawi, Mali, Rwanda, Senegal, Sierra Leone, Tajikistan, Vietnam. Analysis considered adolescent health content (mindset), indicators (measure) and funding (money) relative to adolescent sexual and reproductive health needs, using a tracer indicator. RESULTS:  Countries with higher rates of adolescent pregnancy had more content relating to adolescent reproductive health, with exceptions in fragile contexts. Investment cases had more adolescent content than project appraisal documents. Content gradually weakened from mindset to measures to money. Related conditions, such as fistula, abortion, and mental health, were insufficiently addressed. Documents from Burkina Faso and Malawi demonstrated it is possible to include adolescent programming even within a context of shifting or selective priorities. CONCLUSION: Tracing prioritisation and translation of commitments into plans provides a foundation for discussing global funding for adolescents. We highlight positive aspects of programming and areas for strengthening and suggest broadening the perspective of adolescent health beyond the reproductive health to encompass issues, such as mental health. This paper forms part of a growing body of accountability literature, supporting advocacy work for adolescent programming and funding.

Main findings: Adolescent health content is inconsistently included in the Global Financing Facility country documents, and despite strong or positive examples, the content is stronger in investment cases than project appraisal documents, and diminishes when comparing content, indicators and financing.Added knowledge: Although adolescent health content is generally strongest in countries with the highest proportion of births before age 18, there are exceptions in fragile contexts and gaps in addressing important issues related to adolescent health.Global health impact for policy and action: Adolescent health programming supported by the Global Financing Facility should build on examples of strong country plans, be more consistent in addressing adolescent health, and be accompanied by public transparency to facilitate accountability work such as this.

A Mixed-Method Study on Rural Community's Response to Public Health Emergency in the Philippines: Lessons from the First Wave of the COVID-19 Pandemic.

Background: People from rural communities are not spared from COVID-19. But implementing preventive measures and strategies can be made to control the spread. Objective: This study was conducted to describe the epidemiologic situation and the healthcare capacity of the locality, determine the responses and strategies implemented in the control of COVID-19, and explain the activities performed in relation to the epidemiologic situation in Tarangnan, Samar - a low-income class municipality in the Philippines. Methods: A mixed qualitative-quantitative design was employed in this study. Descriptive documentary research design through review of records from March to October 2020 was utilized. For the qualitative context, a case study design was employed whereby focus group discussions and key informant interviews using open-ended questions were performed. Results: A total of 66 individuals were recorded as having COVID-19 in the municipality from March to October 2020. The first recorded confirmed cases of COVID-19 in Eastern Visayas were two adults in Tarangnan, Samar, in March 2020. Since then, additional confirmed cases have been recorded every month, but confirmed COVID-19 dramatically reduced from August to October 2020. Qualitative analysis revealed stringent COVID-19 preventive measures reflected in the confirmed case numbers. The tailwinds of the COVID-19 response include: the SARS pandemic precedent, coordination and communication, outpouring of support from other government and non-government partners, and innovative community-based approaches. The headwinds of COVID-19 response were challenges in imposing minimum health and safety precautions, stigmatization, and discrimination. Conclusion: Even if challenges have arisen in implementing measures against the spread of the disease, good outcomes have been achieved through persistent good practice, positive modifications, and community-based innovations.

Dyadic body competence predicts movement synchrony during the mirror game.

The process of synchronizing our body movements with others is known to enhance rapport, affect, and prosociality. Furthermore, emerging evidence suggests that synchronizing activities may enhance cognitive performance. Unknown, by contrast, is the extent to which people's individual traits and experiences influence their ability to achieve and maintain movement synchrony with another person, which is key for unlocking the social and affective benefits of movement synchrony. Here, we take a dyad-centered approach to gain a deeper understanding of the role of embodiment in achieving and maintaining movement synchrony. Using existing data, we explored the relationship between body competence and body perception scores at the level of the dyad, and the dyad's movement synchrony and complexity while playing a 2.5-min movement mirroring game. The data revealed that dyadic body competence scores positively correlate with movement synchrony, but not complexity, and that dyadic body perception scores are not associated with movement synchrony or complexity. Movement synchrony was greater when the more experienced member of the dyad was responsible for copying movements. Finally, movement synchrony and complexity were stable across the duration of the mirror game. These findings show that movement synchrony is sensitive to the composition of the dyad involved, specifically the dyad's embodiment, illuminating the value of dyadic approaches to understanding body movements in social contexts.

REALITIES in health disparities: Researching Evidence-based Alternatives in Living, Imaginative, Traumatised, Integrated, Embodied Systems.

Introduction: Under the backdrop of pervasive health inequalities, public health professionals, researchers and non-academic partners in the United Kingdom are mobilising to understand how and in what ways community assets can address health disparities at scale in complex systems. While there is recognition that cultural, natural and community resources can improve health outcomes, these are unequally dispersed with lack of integration in communities and health and social care systems. Researching Evidence-based Alternatives in Living, Imaginative, Traumatised, Integrated, Embodied Systems (REALITIES) is a participatory action research Scottish consortium of 57 with established community asset hubs in five localities with strong relationships uniting conflicting ways of seeing the world. Our collective of lived and felt experience community members, community-embedded researchers, academics and non-academics draws upon a variety of practices, methods, datasets and philosophies to expand existing approaches to tackling health inequalities. Methods: We present conceptual and theoretical underpinnings for our co-produced systems-level model and empirical findings from testing REALITIES across three disadvantaged localities (November 2022, ongoing). After explaining the context that led to the development of the new scalable REALITIES model for integrated public systems to interface with 'assets', we detail philosophical pillars and guiding principles for our model and how we applied these mechanisms to explain how integrated partnership working can lead to improved health outcomes across multiple public systems. Results: We present a meta-analysis from co-producing and testing the model, showing how measuring change in complex public systems involves critical investigation of People, Process, Place, Price, Power and Purpose. Our critique reflects on power imbalances and inequities in Research-practice-Policy (RPP) partnerships and suggestions for how to nurture healthy ecosystems: overcoming barriers and enabling participation; reflecting on challenges of scaling up, testability and complexity of RPP partnerships; moving from siloed learning to transdisciplinary collaboration in practice; ensuring knowledge exchange has direct impact on communities and frontline practitioners; embedding relational ethics and safeguarding into daily practice. Discussion: We propose the REALITIES model to unite alternative, sometimes conflicting, ways of thinking about public systems and community assets by continuously reflecting on entanglements between different assumptions about knowledge, reality, evidence, and unnecessary binaries between creative methodologies and scientific method.

Health beliefs of unmarried adult Saudi individuals toward safe marriage and the role of premarital screening in avoiding consanguinity: a nationwide cross-sectional study.

Introduction: Premarital screening (PMS) is an essential global measure that seeks to reduce the occurrence of specific genetic disorders and sexually transmitted diseases common in consanguineous marriages. Due to the lack of a nationwide study, this research was designed to comprehend how unmarried individuals perceive the risks and benefits of PMS. Method: A cross-sectional study was conducted using an online questionnaire distributed through different social media platforms, responses from the native adult population (18-49 years) Saudi Arabia was only included in the study. The questionnaire was based on the Health Belief Model (HBM) to assessing seven different constructs including susceptibility, seriousness, benefits-, barriers-, & cues- to action, self-efficacy, and social acceptance. Data frequency was represented by mean and standard deviation; chi-square and t-tests were conducted for the comparison of independent and dependent variables. A multinomial logistic regression was used to predict factors influencing decisions related to PMS. Results: 1,522 participants completed the survey, mostly 18-25 years old and most of them were women. The majority were single with 85 men and 1,370 women. Most participants (59.6%) believed their parents were related, while 40.5% did not. 122 respondents reported they had to marry within their tribe. Findings revealed significant correlations among all HBM themes, with varying strengths. Notably, a moderate positive relationship was found between the perception of benefits and cues to action, suggesting that enhancing the perceived benefits of PMS could facilitate safe marriage practices. Multinomial regression analysis revealed that demographic factors and health beliefs significantly influence individuals' intentions and behaviors toward PMS and safe marriage. Conclusion: The study concludes that by identifying and addressing barriers, and promoting positive social acceptance, PMS can significantly contribute to preventing genetic diseases and promoting safe marriage practices, although the cross-sectional design limits the establishment of causal relationships and further research is needed.

Synthesis of aminopropyl triethoxysilane/melamine incorporated superhydrophilic membranes for simultaneous removal of oil, metals, and Salt ions from produced water.

Water treatment has turned out to be more important in most societies due to the expansion of most economies and to advancement of industrialization. Developing efficient materials and technologies for water treatment is of high interest. Thin film nanocomposite membranes are regarded as the most effective membranes available for salts, hydrocarbon, and environmental pollutants removal. These membranes improve productivity while using less energy than conventional asymmetric membranes. Here, the polyvinylidene fluoride (PVDF) membranes have been successfully modified via dip single-step coating by silica-aminopropyl triethoxysilane/trimesic acid/melamine nanocomposite (Si-APTES-TA-MM). The developed membranes were evaluated for separating the emulsified oil/water mixture, the surface wettability of the membrane materials is therefore essential. During the conditioning step, that is when the freshwater was introduced, the prepared membrane reached a flux of about 27.77 L m-2 h-1. However, when the contaminated water was introduced, the flux reached 18 L m-2 h-1, alongside an applied pressure of 400 kPa. Interestingly, during the first 8 h of the filtration test, the membrane showed 90 % rejection for ions including Mg2+, and SO42- and ≈100 % for organic pollutants including pentane, isooctane, toluene, and hexadecane. Also, the membrane showed 98 % rejection for heavy metals including strontium, lead, and cobalt ions. As per the results, the membrane could be recommended as a promising candidate to be used for a mixture of salt ions, hydrocarbons, and mixtures of heavy metals from wastewater.

The pollutant perfluorohexane sulfonate (PFHxS) reduces serum thyroxine but does not alter thyroid action in the postnatal rat brain.

Known as "forever chemicals", per- and polyfluoroalkyl substances (PFAS) are synthetic compounds used in consumer goods but pose significant public health concerns, including disruption of the thyroid system. As thyroid hormones (THs) are required for normal brain development, PFAS may also be developmental neurotoxicants. However, this is not well understood. Here we examine the endocrine and neurodevelopmental consequences of perfluorohexane sulfonate (PFHxS) exposure in pregnant, lactating, and developing rats, and compare its effects to an anti-thyroid pharmaceutical (propylthiouracil, PTU) that induces thyroid-mediated developmental neurotoxicity. We show that PFHxS dramatically reduces maternal serum thyroxine (T4), nearly equivalently to PTU (-55 and -51%, respectively). However, only PTU increases thyroid stimulating hormone. The lactational transfer of PFHxS is significant and reduces pup serum T4 across the postnatal period. Surprisingly, brain THs are only minimally decreased by PFHxS, whereas PTU drastically diminishes them. Evaluation of brain TH action by phenotyping, RNA-Sequencing, and quantification of radial glia cell morphology supports that PTU interrupts TH signaling while PFHxS has limited to no effect. These data show that PFHxS induces abnormal serum TH profiles; however, there were no indications of hypothyroidism in the postnatal brain. We suggest the stark differences between the neurodevelopmental effects of PFHxS and a typical antithyroid agent may be due to its interaction with TH distributing proteins like transthyretin.

[Research progress on the developmental toxicity and mechanism of brominated flame retardants during pregnancy exposure on offspring].

Brominated flame retardants (BFRs) are a kind of brominated compounds widely used in electronic and electrical appliances, textiles, construction materials and other industrial products to improve the flame retardant property. Because of its strong chemical stability, environmental persistence, long-distance transmission, biological accumulation, the exposure of humans and organisms in the ecosystem is increasing, and its potential biological effects are of great concern. Now BFRs can be detected in breast milk, serum, placenta and cord blood. Studies have shown that exposure to BFRs during pregnancy can lead to adverse birth outcomes such as low birth weight, malformation, gestational age changes and impairment of neurobehavioral development. This article summarizes the pollution and population exposure of three traditional BFRs, polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA), as well as the impact and mechanism of prenatal exposure on offspring birth outcomes and growth and development. It explores the harm of prenatal exposure to BFRs to offspring and proposes preventive measures for occupational populations for reference.

No Differences in Kidney Function Decline Between People With Type 2 Diabetes Starting a Sodium-Glucose Cotransporter 2 Inhibitor or a Glucagon-like Peptide-1 Receptor Agonist: A Real-world Retrospective Comparative Observational Study.

PURPOSE: Diabetic nephropathy represents the leading cause of end-stage kidney disease in developed countries. Cardiovascular outcome trials have found that in participants who received a glucagon-like peptide-1 receptor agonist (GLP1RA) and a sodium-glucose cotransporter 2 inhibitor (SGLT2i), the risk of incidence and progression of diabetic nephropathy in type 2 diabetes mellitus was reduced. The aim of this study was to compare the decline in estimated glomerular filtration rate (eGFR) among people taking a GLP1RA with that among people taking an SGLT2i in a real-world setting. METHODS: Data for 478 patients with type 2 diabetes mellitus who initiated therapy with a GLP1RA (n = 254) or an SGLT2i (n = 224) between January 1, 2018 and December 31, 2021 were extracted. The primary outcome was any reduction ≥30% in eGFR after the start of therapy. Weight loss and drug discontinuation were also assessed. FINDINGS: Over a median follow-up of 24 months, an eGFR reduction ≥30% occurred in 34 of 254 patients (13.4%) starting a GLP1RA and in 26 of 223 patients (11.6%) starting an SGLT2i (hazard ratio = 0.89; 95% CI, 0.54-1.49; P = 0.67). Median eGFR change over the whole follow-up was similar between groups (SGLT2i: median, -2 mL/min/1.73 m2; 25th, 75th percentile, -13, 8 mL/min/1.73 m2; GLP1RA: median, 0 mL/min/1.73 m2; 25th, 75th percentile, -10, 7 mL/min/1.73 m2; P = 0.54). No worsening of kidney function was observed, even when considering the ratio eGFR mean. The value of eGFR at baseline indicated a statistically significant indirect correlation with the observed absolute value of eGFR change over the follow-up (ρ = -0.36; P < 0.001). The difference in eGFR changes over time observed by eGFR categories was statistically significant (P = 0.0001) in both treatment groups. No significant differences in weight loss and drug discontinuations were observed between groups. IMPLICATIONS: Although acting on different molecular mechanisms, both GLP1RA and SGLT2i might have similar effects on eGFR decline in diabetes, as suggested by the results of the present study conducted in a real-world setting. (Clin Ther. 2024;46:XXX-XXX) © 2024 Elsevier HS Journals, Inc.

The Role of Probiotics in Skin Care: Advances, Challenges, and Future Needs.

The skin, being the largest organ in the human body, plays a pivotal role in safeguarding the body against invasive pathogens. Therefore, it is essential to reinforce and protect this vital organ. Current research supports the impact of probiotics on skin health and their ability to alleviate various skin disorders. However, the effectiveness and probable side effects of probiotics in skin care remain a subject of debate, necessitating further investigation and analysis. Hence, this study aims to highlight existing gaps and future needs in the current research on probiotics in skin care and pave the way for future investigations. Therefore, we scrutinized the effects of oral (fermented foods and dietary supplements) and non-oral/topical probiotics on skin care, and the mechanism of probiotics that affect skin health. The results of most studies showed that fermented foods containing probiotics, particularly dairy products, positively impact skin health. The research results regarding the efficacy of probiotic supplements and live strains in treating skin disorders show promising potential. However, safety evaluations are crucial, to identify any potential adverse effects. While research has identified numerous potential mechanisms by which probiotics may influence skin health, a complete understanding of their precise mode of action remains elusive. However, it seems that probiotics can exert their positive effects through the gut-skin and gut-skin-brain axis on the human body. Therefore, following the identification of safe probiotics, additional studies should be carried out to establish optimal dosages, potential side effects, suitable regulatory guidelines, and validation methods.

Advances in the anti-tumor mechanisms of saikosaponin D.

Saikosaponin D, a saponin compound, is extracted from Bupleurum and is a principal active component of the plant. It boasts a variety of pharmacologic effects including anti-inflammatory, antioxidant, immunomodulatory, metabolic, and anti-tumor properties, drawing significant attention in anti-tumor research in recent years. Research indicates that saikosaponin D inhibits the proliferation of numerous tumor cells, curbing the progression of cancers such as liver, pancreatic, lung, glioma, ovarian, thyroid, stomach, and breast cancer. Its anti-tumor mechanisms largely involve inhibiting tumor cell proliferation, promoting tumor cell apoptosis, thwarting tumor-cell invasion, and modulating tumor cell autophagy. Moreover, saikosaponin D enhances the sensitivity to anti-tumor drugs and augments body immunity. Given its multi-faceted anti-tumor roles, saikosaponin D offers promising potential in anti-tumor therapy. This paper reviews recent studies on its anti-tumor effects, aiming to furnish new theoretical insights for clinical cancer treatments.

Novel therapeutic strategies and drugs for idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease of unknown etiology. Currently, drugs used to treat IPF in clinical practice exhibit severe side effects and limitations. To address these issues, this paper discusses the therapeutic effects of preclinical targeted drugs (such as STAT3 and TGF-ß/Smad pathway inhibitors, chitinase inhibitors, PI3K and phosphodiesterase inhibitors, etc.) and natural products on IPF. Through a summary of current research progress, it is found that natural products possess multitarget effects, stable therapeutic efficacy, low side effects, and nondrug dependence. Furthermore, we discuss the significant prospects of natural product molecules in combating fibrosis by influencing the immune system, expecting that current analytical data will aid in the development of new drugs or the investigation of active ingredients in natural products for potential IPF treatments in the future.

Design, synthesis, antimicrobial activity, and mechanism of novel 3-(2,4-dichlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives.

BACKGROUND: Plant pathogens cause substantial crop losses annually, posing a grave threat to global food security. Fungicides have usually been used for their control, but the rapid development of pesticide resistance renders many ineffective, therefore the search for novel and efficient green pesticides to prevent and control plant diseases has become the top priority in crop planting. RESULTS: The results of bioassay studies indicated that most of the target compounds showed certain antimicrobial activity in vitro. In particular, compound X7 showed high inhibitory activity against Xanthomonas oryzae pv. oryzae (Xoo), with an EC50 value of 27.47 µg mL-1, surpassing conventional control agents such as thiazole zinc (41.55 µg mL-1) and thiodiazole copper (53.39 µg mL-1). Further studies on molecular docking showed that X7 had a strong binding affinity with 2FBW. The morphological change observed by scanning electron microscopy indicated that the surface of Xoo appears wrinkled and cracked under X7 treatment and a total of 2662 proteins were identified by label-free proteomic analysis. Three experiments have elucidated the mechanism whereby X7 induced considerable changes in the physiological and biochemical properties of Xoo, which in turn affected the reproduction and growth of bacteria. CONCLUSION: This work represents a pivotal advancement, offering important reference for the research and development therapeutics in combating plant pathogens. © 2024 Society of Chemical Industry.

F wave analysis based on the compound muscle action potential scan.

INTRODUCTION/AIMS: Conventional F wave analysis involves a relatively uniform physiological environment induced by supramaximal stimulations. The F wave characteristics in a dynamic physiological condition, however, are rarely investigated. This study aimed to improve understanding of F wave properties in the more dynamic process by introducing a novel method to analyze F waves based on the compound muscle action potential (CMAP) scan technique. METHODS: Twenty four healthy subjects participated in the study. The CMAP scan was applied to record muscle responses in the abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles, respectively. F wave characteristics including mean F wave amplitude and latency (F-M latency), persistence and activating threshold were quantified. RESULTS: An average of 200 F waves per muscle were obtained from the CMAP scan recording. Weak to moderate correlations between F wave amplitude and stimulating intensity were observed in most of the APB (19 muscles; r = 0.33 ± 0.14, all p < .05) and ADM (23 muscles, r = 0.46 ± 0.16, all p < .05) muscles. Significantly longer mean F latency and lower activating F-threshold were found in the ADM muscles (F-M latency: APB: 25.43 ± 2.39 ms, ADM: 26.15 ± 2.32 ms, p < .05; F-threshold: APB: 7.68 ± 8.96% CMAP, ADM: 2.35 ± 2.42% CMAP, p < .05). DISCUSSION: This study introduces new features of F waves using the CMAP scan technique and identifies differences of F wave characteristics between the hand muscles. The CMAP scan based F waves analysis can be combined with the motor unit number estimation to assess functional alterations in motor neurons in neurological disorders.

Observers predict actions from facial emotional expressions during real-time social interactions.

In face-to-face social interactions, emotional expressions provide insights into the mental state of an interactive partner. This information can be crucial to infer action intentions and react towards another person's actions. Here we investigate how facial emotional expressions impact subjective experience and physiological and behavioral responses to social actions during real-time interactions. Thirty-two participants interacted with virtual agents while fully immersed in Virtual Reality. Agents displayed an angry or happy facial expression before they directed an appetitive (fist bump) or aversive (punch) social action towards the participant. Participants responded to these actions, either by reciprocating the fist bump or by defending the punch. For all interactions, subjective experience was measured using ratings. In addition, physiological responses (electrodermal activity, electrocardiogram) and participants' response times were recorded. Aversive actions were judged to be more arousing and less pleasant relative to appetitive actions. In addition, angry expressions increased heart rate relative to happy expressions. Crucially, interaction effects between facial emotional expression and action were observed. Angry expressions reduced pleasantness stronger for appetitive compared to aversive actions. Furthermore, skin conductance responses to aversive actions were increased for happy compared to angry expressions and reaction times were faster to aversive compared to appetitive actions when agents showed an angry expression. These results indicate that observers used facial emotional expression to generate expectations for particular actions. Consequently, the present study demonstrates that observers integrate information from facial emotional expressions with actions during social interactions.

An in vitro antiviral evaluation of punicalagin toward influenza A virus.

Objective: Influenza complications are mild to serious, and can cause death in some cases. A great deal of attention has been paid in recent years to the development and use of new antiviral compounds to overcome drug resistance in certain strains of the influenza virus and treat the clinical implications. This study aimed to investigate the antiviral effect of punicalagin and its associated mechanism against influenza A (H1N1) virus in vitro. Materials and Methods: the ant-influenza activity of punicalagin was studied in Madin-Darby Canine Kidney (MDCK) cells using influenza virus A/Puerto Rico/8/34 (H1N1) (PR8) using Hemagglutinin assay (HA) and 50% tissue culture infective dose (TCID50). Then, the inhibition of haemagglutination, virucidal activity, inhibitory effect at different times, replication of viral RNA and expression of viral genes were investigated. Results: Punicalagin could inhibit influenza virus infection with 50% inhibitory concentration (IC50) of 3.98 µg/ml and selectivity index (SI) value of 6.1. Punicalagin decreased virus titers with an inhibitory effect on virus hemagglutination (p<0.05). Punicalagin also inhibited viral adsorption. The results of virus RNA replication and viral mRNA (NS1 and HA) expression after treatment with punicalagin showed significant suppression of viral mRNA expression but no effect on replication of viral RNA. Conclusion: The results of the present study indicated that punicalagin was effective against influenza infection most probably via inhibition of haemagglutination activity and virus binding.