Direct diffusion of anti-Müllerian hormone from both the cranial and caudal regions of the testis during early gonadal development in mice.

BACKGROUND: The Müllerian duct (MD), the primordium of the female reproductive tract, is also formed in males during the early stage of development, then regresses due to the anti-Müllerian hormone (AMH) secreted from the testes. However, the detailed diffusion pathway of AMH remains unclear. We herein investigated the mechanism by which AMH reaches the middle region of the MD using an organ culture system. RESULTS: Injection of recombinant human AMH into the testis around the start of MD regression induced diffuse immunoreactivity in the mesonephros near the injection site. When the testis and mesonephros were cultured separately, the diameters of both cranial and middle MDs were significantly increased compared to the control. In the testis-mesonephros complex cultured by inhibiting the diffusion of AMH through the cranial region, the cranial MD diameter was significantly increased compared to the control, and there was no difference in middle MD diameter. CONCLUSIONS: These results indicate that AMH, which infiltrates from the testis through the cranial region at physiological concentrations, induces regression of the cranial MD at the start of MD regression. They also indicate that AMH infiltrating through the caudal regions induces regression of the middle MD.

From flesh to bones: Multi-omics approaches in forensic science.

Recent advancements in omics techniques have revolutionised the study of biological systems, enabling the generation of high-throughput biomolecular data. These innovations have found diverse applications, ranging from personalised medicine to forensic sciences. While the investigation of multiple aspects of cells, tissues or entire organisms through the integration of various omics approaches (such as genomics, epigenomics, metagenomics, transcriptomics, proteomics and metabolomics) has already been established in fields like biomedicine and cancer biology, its full potential in forensic sciences remains only partially explored. In this review, we have presented a comprehensive overview of state-of-the-art analytical platforms employed in omics research, with specific emphasis on their application in the forensic field for the identification of the cadaver and the cause of death. Moreover, we have conducted a critical analysis of the computational integration of omics approaches, and highlighted the latest advancements in employing multi-omics techniques for forensic investigations.

Zebrafish TMEM47 is an effective blocker of IFN production during RNA and DNA virus infection.

IMPORTANCE: Mitochondrial antiviral signaling protein (MAVS) and stimulator of interferon (IFN) genes (STING) are key adaptor proteins required for innate immune responses to RNA and DNA virus infection. Here, we show that zebrafish transmembrane protein 47 (TMEM47) plays a critical role in regulating MAVS- and STING-triggered IFN production in a negative feedback manner. TMEM47 interacted with MAVS and STING for autophagic degradation, and ATG5 was essential for this process. These findings suggest the inhibitory function of TMEM47 on MAVS- and STING-mediated signaling responses during RNA and DNA virus infection.

Manipulating host secreted protein gene expression: an indirect approach by HPV11/16 E6/E7 to suppress PBMC cytokine secretion.

Human papillomavirus (HPV) 11/16 E6/E7 proteins have been recognized to be pivotal in viral pathogenesis. This study sought to uncover the potential mechanisms of how HPV11/16 E6/E7-transfected keratinocytes inhibit cytokine secretion in peripheral blood mononuclear cells (PBMC). Upon co-culturing HPV11/16 E6/E7-transfected keratinocytes with PBMC in a non-contact manner, we observed a marked decrease in various cytokines secreted by PBMC. To determine if this suppression was mediated by specific common secreted factors, we conducted transcriptomic sequencing on these transfected cells. This analysis identified 53 common differentially secreted genes in all four HPV-transfected cells. Bioinformatics analysis demonstrated these genes were predominantly involved in immune regulation. Results from quantitative PCR (qPCR) and an extensive literature review suggested the downregulation of 12 genes (ACE2, BMP3, BPIFB1, CLU, CST6, CTF1, HMGB2, MMP12, PDGFA, RNASE7, SULF2, TGM2), and upregulation of 7 genes (CCL17, CCL22, FBLN1, PLAU, S100A7, S100A8, S100A9), may be crucial in modulating tumor immunity and combating pathogenic infections, with genes S100A8 and S100A9, and IL-17 signaling pathway being particularly noteworthy. Thus, HPV11/16 E6/E7 proteins may inhibit cytokine secretion of immune cells by altering the expression of host-secreted genes. Further exploration of these genes may yield new insights into the complex dynamics of HPV infection.

FTO promotes cervical cancer cell proliferation, colony formation, migration and invasion via the regulation of the BMP4/Hippo/YAP1/TAZ pathway.

Cervical cancer is the fourth most common malignancy tumor worldwide with high incidence and mortality. Accumulating evidence indicated that through an m6A-dependent or m6A-independent mechanism, fat mass and obesity associated gene (FTO) exhibits the tumor-promoting and suppressive roles of FTO involved in various cancers, including cervical cancer. This study aims to verify the biological function and potential mechanisms of FTO in cervical cancer cell proliferation, colony formation, migration, and invasion in vitro as well as tumor growth in vivo. Herein, we confirmed that knockdown of FTO inhibits cell proliferation, colony formation, migration, and invasion of cervical cancer cells in vitro via cell counting kit-8 (CCK8) assay, colony formation assay, and transwell migration and invasion assay. The demethylase activity of FTO is required for cell proliferation, colony formation, migration, and invasion of cervical cancer cells in vitro. RNA sequencing, online database analysis, and western blotting revealed that FTO regulated the BMP4/Hippo/YAP1/TAZ pathway. In addition, FTO upregulates the expression of BMP4 in an m6A-dependent manner and binds to the N-terminal of BMP4 to form a dimer at the C-terminal in cervical cancer cells through protein-protein interaction. We further discovered that BMP4 treatment promoted cell proliferation, colony formation, migration, and invasion of cervical cancer cells, and rescue experiments validated that BMP4 treatment reversed the inhibition of FTO knockdown on the Hippo/YAP1/TAZ pathway and the progression of cervical cancer cells in vitro. Notably, the knockdown of FTO significantly suppressed xenograft tumor growth and the protein level of BMP4 in vivo. Collectively, our results demonstrate that the FTO promotes cervical cancer progression in vitro and in vivo via the regulation of the BMP4/Hippo/YAP1/TAZ pathway, suggesting that FTO acts as an oncogenic molecule and the FTO/BMP4 Hippo/YAP1/TAZ axis may serve as valuable targets for cervical cancer treatment.

The protection motivation theory as an explanatory model for intention to use alcohol protective behavioral strategies related to the manner of drinking among young adults.

AIMS: This study aimed to prospectively examine the explanatory value of the protection motivation theory (PMT) for the intention to use manner of drinking protective behavioral strategies (MD PBS) and to explore its invariance across genders. METHOD: A targeted sampling procedure was used to recruit 339 young adults in the community (Mage = 21.1; SD = 2.21; female = 50.7%) who completed baseline and 2-month follow-up measures of the PMT constructs and intentions to use each of the five MD PBS. RESULTS: Regression analyses revealed that the coping appraisal components (response efficacy and self-efficacy) had greater explanatory power for the intention to use MD PBS than the threat appraisal components (perceived vulnerability and perceived severity). Perceived vulnerability to alcohol consequences was not prospectively associated with any specific behavioral intention or with the total MD PBS score. In contrast, perceived severity was prospectively associated with the intention to use three out of five PBS and the total MD score. Regression coefficients revealed gender invariance for all six models. CONCLUSIONS: Our findings suggest that interventions aimed at encouraging young adults to use alcohol MD PBS would be most effective if they included components that enhance self-efficacy in using these strategies and emphasize their perceived usefulness in reducing alcohol-related consequences.

The majority of negative online otolaryngology reviews are non-clinical.

OBJECTIVE: To characterize extremely negative online reviews of Otolaryngologists in the United States. METHODS: A search for reviews was performed on Yelp.com using the keyword "Otolaryngologist" in four major urban cities in the United States. On a five-star scale, one-star reviews were isolated, classified as clinical or non-clinical complaints, and further subcategorized. Chi-square analysis was used to determine differences in complaint types between patients reporting surgery and those who did not. RESULTS: From the 7653 reviews that were surveyed, 375 one-star reviews met the inclusion criteria and were used in the analysis. These negative reviews yielded 808 total complaints, 25 % were clinical, and 75 % were non-clinical. The most common clinical complaints were a lack of diagnosis, disagreement with the treatment plan and misdiagnosis, whereas the most common non-clinical complaints included poor physician bedside manner, cost, and unprofessional staff. Fifty-two (14 %) patients reported having surgery. The difference in the number of complaints by patients reporting surgery and patients not reporting surgery was statistically significant (P < .05) for almost all subcategories. CONCLUSION: The most common complaints in negative reviews of Otolaryngologists on Yelp are non-clinical, primarily centered around the professionalism of the physician and staff. This work offers insights into patient satisfaction within Otolaryngology. Considerations should be given to these results as a means for improvement in patient experiences.

In vitro and in silico investigation of FDA-approved drugs to be repurposed against Alzheimer's disease.

Alzheimer's disease (AD), one of the main causes of dementia, is a neurodegenerative disorder. Cholinesterase inhibitors are used in the treatment of AD, but prolonged use of these drugs can lead to serious side effects. Drug repurposing is an approach that aims to reveal the effectiveness of drugs in different diseases beyond their clinical uses. In this work, we investigated in vitro and in silico inhibitory effects of 11 different drugs on cholinesterases. The results showed that trimebutine, theophylline, and levamisole had the highest acetylcholinesterase inhibitory actions among the tested drugs, and these drugs inhibited by 68.70 ± 0.46, 53.25 ± 3.40, and 44.03 ± 1.20%, respectively at 1000 µM. In addition, these drugs are bound to acetylcholinesterase via competitive manner. Molecular modeling predicted good fitness in acetylcholinesterase active site for these drugs and possible central nervous system action for trimebutine. All of these results demonstrated that trimebutine was determined to be the drug with the highest potential for use in AD.

Effect of Bridging Manner on the Transport Behaviors of Dimethyldihydropyrene/Cyclophanediene Molecular Devices.

A molecule-electrode interface with different coupling strengths is one of the greatest challenges in fabricating reliable molecular switches. In this paper, the effects of bridging manner on the transport behaviors of a dimethyldihydropyrene/cyclophanediene (DHP/CPD) molecule connected to two graphene nanoribbon (GNR) electrodes have been investigated by using the non-equilibrium Green's function combined with density functional theory. The results show that both current values and ON/OFF ratios can be modulated to more than three orders of magnitude by changing bridging manner. Bias-dependent transmission spectra and molecule-projected self-consistent Hamiltonians are used to illustrate the conductance and switching feature. Furthermore, we demonstrate that the bridging manner modulates the electron transport by changing the energy level alignment between the molecule and the GNR electrodes. This work highlights the ability to achieve distinct conductance and switching performance in single-molecular junctions by varying bridging manners between DHP/CPD molecules and GNR electrodes, thus offering practical insights for designing molecular switches.

Commentary on "Fatal cardiac air embolism after CT-guided percutaneous needle lung biopsy: medical complication or medical malpractice?"

To differentiate between medical malpractice and expected, but rare, medical complication in a medicolegal autopsy context is often difficult. Such an assessment requires knowledge about the clinical practice associated with the procedure at hand, and that findings of the autopsy, including medical relevant information such as patient chart, radiological imaging, and statements from witnesses about the medical procedure itself, provides evidence that substantiate either conclusion. In a case report published in the journal such an assessment is discussed by presenting findings and circumstances surrounding the death of a patient during a percutaneous needle lung biopsy procedure. The authors conclude that the death was not due to medical malpractice. However, in this commentary it is highlighted that the reasoning behind the conclusion needs to be further substantiated.

Identification of key variants correlated with susceptibility of primary osteoporosis in the Chinese Han group.

BACKGROUND: Primary osteoporosis is a systemic skeletal disease characterized by reduced bone mass and vulnerability to fractures. The genetics of osteoporosis in the Chinese population remain unclear, which hinders the prevention and treatment of osteoporosis in China. This study aimed to explore the susceptibility genes and the roles played by their variants in osteoporosis. METHODS: Blood samples were collected from 45 osteoporosis patients and 30 healthy individuals, and genome-wide association study was performed on array data. The expression levels of the candidate gene in different genotypes were further determined by using quantitative real-time PCR. Moreover, the differentiation capacity of bone marrow mesenchymal stem cells under different genotypes from osteoporosis patients was investigated. RESULTS: The most significant variant rs1891632 located in the upstream (918 bp) region of CRB2, which could down-regulate the expression levels of CRB2 in genotype-tissue expression database and played an essential role in the regulation of osteoblastic and osteoclastic differentiation during skeletal development. Another significant variant rs1061657 located within the 3'UTR region of TBX3 gene. We found that the mRNA levels of TBX3 decreased in the bMSCs of old osteoporosis patients. Interestingly, osteoblast differentiation capacity and TBX3 mRNA levels were similar between the young healthy individuals carrying derived and ancestral allele of rs1061657, whereas the differentiation capacity and TBX3 mRNA levels dramatically declined in elderly patients with osteoporosis. CONCLUSIONS: The variant rs1061657 might affect the osteogenesis of bMSCs in an age-dependent manner and that TBX3 may be a key susceptibility gene for primary osteoporosis. In conclusion, CRB2 and TBX3 may influence the development of osteoporosis; additionally, rs1891632 and rs1061657, as the key variants first reported to be associated with primary osteoporosis, may potentially contribute to predicting the risk of osteoporosis (especially for older individuals) and may serve as therapeutic targets.

Evaluation of the cardiovascular risk induced by cannabis use from a series of 43 autopsy cases.

The aim of this monocentric observational autopsy study was to confirm the existence of a link between cannabis use and cardiovascular risk. It was based on the analysis of autopsy findings, cardiovascular pathological findings, and toxicological data in 43 autopsy cases of people who died with tetrahydrocannabinol (THC) in their blood over a 2-year period. Hair analysis was performed when available (n = 40) to distinguish between occasional and chronic cannabis use and to take into account other possible exposures, including smoking, drug consumption, and the use of other drugs of abuse (mainly cocaine, heroin, and amphetamine). A statistically significant association (Fisher's exact test, p < 0.001) was found between cannabis use, an undetermined manner of death, and the presence of an arrhythmogenic cardiac condition. An association was also found between cannabis use and the presence of advanced coronary heart disease (p = 0.01), heart disease (including ischemic heart disease, p = 0.003), or cardiomyopathy (p = 0.01). Through its systemic vascular action, cannabis could be a factor in triggering sudden death in subjects with arrhythmogenic cardiac conditions. In view of this finding, the mode of death of subjects who died in the presence of THC in the blood would in most cases be an "accident." These results highlight the potential adverse cardiac effects associated with cannabis use.

Decreased miR-329-3p upregulates Adamts4 and Dnajb1 in mouse hepatic I/R injury in an age-independent manner.

Introduction: Hepatic ischemia/reperfusion (I/R) injury is common after liver surgery, particularly in patients of older age. However, an understanding of the mechanism of injury remains incomplete. In this study, we explored the molecular mechanisms underlying hepatic I/R injury and associations with age in a murine model. Methods: Gene expression profiling datasets (GSE72315 and GSE10654) and a microRNA (miRNA) expression profiling dataset (GSE72315) were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) and miRNAs (DEMiRs) were identified using online GEO2R or R before and after hepatic I/R injury in mice. Significant Gene Ontology (GO) terms were analyzed with the DAVID functional annotation tool. The DEMiR-miRNA target gene (miRTG) networks were constructed with miRTarBase, and the differentially expressed miRNAs and genes were analyzed with real-time quantitative polymerase chain reaction and immunofluorescence staining. Results: Through bioinformatic analysis, seven novel candidate miRNAs were identified that may regulate the expression of nine genes in hepatic I/R injury. Before and after hepatic I/R injury, mmu-miR-9-5p, mmu-miR-329-3p, and mmu-miR-290a-5p showed significant differential expression both in young (1 month old) and old (1 year old) mice. miR-329-3p had the most significant differential expression, and its predicted target genes Adamts4 and Dnajb1 were also significantly upregulated. Conclusions: The decrease in miR-329-3p expression upregulated Adamts4 and Dnajb1 expression in mouse hepatic I/R injury in an age-independent manner. This finding contributes to our understanding of hepatic I/R injury, and highlights novel molecular targets for future therapeutic development.

Pop Music Singing in Education with Modern Innovative Technologies: How the Chinese Language Shapes the Creation of Popular Singing.

The purpose of this study is to investigate the uniqueness of the pop singing genre by determining the role of the Chinese language in the creation of popular singing in education with modern innovative technologies. The paper began by determining which types of popular music were the most popular among respondents and the influence of modern innovative technologies on music education. The results showed that popular folk music (25%) and popular music (23%) are the most popular genres. This is because they are based on improvisational elements and combine modern and ethnic musical elements with the use of modern innovative technologies. Pentatonic preservation (94.3), modern innovative technologies (91.2), expressive performance (85.6), sound fluidity and mobility (82) and instrumental accompaniment have been identified as the most defining characteristics of contemporary Chinese popular music (78.1). Taking into account how pure and expressive Chinese music is, the study found that singing should take into account the following aspects of the Chinese language: the tonality of vowels, the influence of consonant sounds, the use of sound imitations, the performance of words with different levels of complexity, and the relationship between speech and musical intonation. It has been proven that students in group 1 who studied vocals and were taught the rules for combining phonetic features of language when singing had better results in terms of quality performance (0.83) and expressive performance (0.91). The non-professional singers in group 2 attained scores of 0.62 and 0.85, respectively.

The association of Ned Kelly tattoos with suicide and homicide in a forensic context-a confirmatory prospective study.

Ned Kelly, an iconic figure in contemporary Australian mythology, was a bushranger (outlaw) who was executed in 1880 for the murder of a serving police officer, Constable Thomas Lonigan. Kelly is often commemorated by tattoos which depict his armour and helmet or his alleged last words of "Such is life". A study was undertaken from January 1, 2011, to December 31, 2020, at Forensic Science SA, Adelaide, South Australia, of all cases with such tattoos. De-identified case details included the year of death, age, sex and cause and manner of death. There were 38 cases consisting of 10 natural deaths (26.3%) and 28 unnatural (73.7%). The latter included 15 cases of suicide (39.5%), 9 accidents (23.7%) and 4 homicides (10.5%). Of the 19 suicides and homicides, there were 19 males and no females (age range 24-57 years; average 44 years). The number of suicides in the general South Australian forensic autopsy population in 2020 was 216/1492 (14.5%) which was significantly lower than in the study population in which 39.5% of cases were suicides (2.7 times higher; p < 0.001). A similar trend occurred for homicides which accounted for 17/1492 in the general forensic autopsy population (1.1%), significantly lower than in the study population which had 10.5% homicides (approximately 9.5 times higher; p < 0.001). Thus, in the select population referred for medicolegal autopsy, there appears no doubt that Ned Kelly tattoos are associated with suicides and homicides. While this is not a population-based study, it may provide useful information for forensic practitioners dealing with such cases.

Postmortem injury evaluation using the Forensic Injury Severity Score Template (FISST): a preliminary study.

The Abbreviated Injury Scale (AIS) and Injury Severity Score (ISS) are important evaluation tools used in clinical practice to determine the degree of injury in patients with trauma. However, they are not suitable for forensic practice and their use in forensic applications is limited. This study aimed to present a system that can objectively and quantitatively determine the severity of postmortem injuries and that can be applied to forensic medicine. Subsequently, we applied this system to individual postmortem cases and analyzed the injuries identified during autopsy. We performed a retrospective study of 119 autopsies performed between 2018 and 2021. Data were categorized and analyzed using the Forensic Injury Severity Score Template (FISST), a scoring system developed based on the AIS and ISS. The mean FISST scores were as follows: men, 53.6; women, 46.8; 20-65 years old, 55.6; older than 65 years, 41.4; natural death, 13.8; unnatural death, 66.3; and all deaths, 51.8. Statistically significant differences in the FISST scores were found between natural and unnatural deaths, suicidal and accidental deaths, and trauma-related death subtypes. Injuries identified during autopsy can be objectively and quantitatively evaluated using FISST. We suggest that FISST is a useful tool in forensic medicine because it is tailor-made for injury evaluation from a postmortem perspective.

An awareness-dependent mapping of saliency in the human visual system.

The allocation of exogenously cued spatial attention is governed by a saliency map. Yet, how salience is mapped when multiple salient stimuli are present simultaneously, and how this mapping interacts with awareness remains unclear. These questions were addressed here using either visible or invisible displays presenting two foreground stimuli (whose bars were oriented differently from the bars in the otherwise uniform background): a high salience target and a distractor of varied, lesser salience. Interference, or not, by the distractor with the effective salience of the target served to index a graded or non-graded nature of salience mapping, respectively. The invisible and visible displays were empirically validated by a two-alternative forced choice test (detecting the quadrant of the target) demonstrating subjects' performance at or above chance level, respectively. By combining psychophysics, fMRI, and effective connectivity analysis, we found a graded distribution of salience with awareness, changing to a non-graded distribution without awareness. Crucially, we further revealed that the graded distribution was contingent upon feedback from the posterior intraparietal sulcus (pIPS, especially from the right pIPS), whereas the non-graded distribution was innate to V1. Together, this awareness-dependent mapping of saliency reconciles several previous, seemingly contradictory findings regarding the nature of the saliency map.

Sex-specific effects of bisphenol A on the signaling pathway of ESRRG in the human placenta†.

Bisphenol A (BPA) exposure during pregnancy is associated with low fetal weight, particularly in male fetuses. The expression of estrogen-related receptor gamma (ESRRG), a receptor for BPA in the human placenta, is reduced in fetal growth restriction. This study sought to explore whether ESRRG signaling mediates BPA-induced placental dysfunction and determine whether changes in the ESRRG signaling pathway are sex-specific. Placental villous explants from 18 normal term pregnancies were cultured with a range of BPA concentrations (1 nM-1 µM). Baseline BPA concentrations in the placental tissue used for explant culture ranged from 0.04 to 5.1 nM (average 2.3 ±1.9 nM; n = 6). Expression of ESRRG signaling pathway constituents and cell turnover were quantified. BPA (1 µM) increased ESRRG mRNA expression after 24 h in both sexes. ESRRG mRNA and protein expression was increased in female placentas treated with 1 µM BPA for 24 h but was decreased in male placentas treated with 1 nM or 1 µM for 48 h. Levels of 17ß-hydroxysteroid dehydrogenase type 1 (HSD17B1) and placenta specific-1 (PLAC1), genes downstream of ESRRG, were also affected. HSD17B1 mRNA expression was increased in female placentas by 1 µM BPA; however, 1 nM BPA reduced HSD17B1 and PLAC1 expression in male placentas at 48 h. BPA treatment did not affect rates of proliferation, apoptosis, or syncytiotrophoblast differentiation in cultured villous explants. This study has demonstrated that BPA affects the ESRRG signaling pathway in a sex-specific manner in human placentas and a possible biological mechanism to explain the differential effects of BPA exposure on male and female fetuses observed in epidemiological studies.

Conducting a Professional Telemedicine Visit Using High-Quality Webside Manner.

PURPOSE OF REVIEW: As telemedicine gains popularity among providers and patients alike, it is important to ensure the standards of care remain equivalent between the in-person and virtual settings. While bedside manner remains a key competency incorporated into medical school curricula, "webside manner," or professional standards for virtual care, remains less defined. RECENT FINDINGS: Best practices exist including guidance prior to the visit, methods to maintain a professional background environment, and translation of core communication competencies for a video interaction. Through application of these practices, a provider can ensure the core interpersonal and communication competencies are fulfilled. These practices have direct application to allergy, asthma, and immunology care. This review provides an overview of best practices for professionalism and patient interaction for virtual care and examines specific applications to allergy, asthma, and immunology visits.

Influencing Factors of Horizontal Movement Distance of Bodies in High Falling Deaths.

OBJECTIVES: To explore the influencing factors of the horizontal distance of bodies in the high falling scene and the feasibility of inferring the falling mode based on it. METHODS: A total of 614 high falling deaths and 15 cases of corpse dumping from high altitudes were collected. The relationship between the horizontal distance and the falling height, as well as the sex, age and manner of death (suicide, accident and corpse dumping) were observed. RESULTS: The horizontal distance increased with the increase of falling height, and the difference among the height groups was statistically significant. The horizontal distance decreased with the increase of the age of the deceased, in each height group, the difference between the group over 60 years old and other age groups was statistically significant (P<0.05). The horizontal distance of male deceased was (1.99±0.27) m, which was greater than that of female deceased (1.88±0.19) m, and the difference was statistically significant in partial height groups (P<0.05). Roof falls had a greater horizontal movement distance than window falls. Except for the >20-30 m group, there was no significant difference in horizontal distance between suicide high falls and accidental high falls in other height groups. CONCLUSIONS: The horizontal distance is affected by the falling height, the sex and age of the victim, and the spatial characteristics of the falling starting point.