Protein inhibitor of activated signal transducer and activator of transcription 2 is an oncoprotein in oral squamous cell carcinoma and related to cigarette smoking - An in vitro study.

Background/purpose: Oral cancer is one of the most prevalent malignant tumors in Taiwan. Due to the heterogeneity of oral cancer cells, the five-year survival rate of patients is only 50%. Post-translational modifications contribute to protein diversity and directly influence cell functions. The protein inhibitor of activated signal transducer and activator of transcription 2 (PIAS2) is known to undergo post-translational modifications, yet its impact on oral cancer remains unclear. Materials and methods: PIAS2 expression was modulated by transfecting cells with a PIAS2 expression vector or by knocking down PIAS2 using siRNA with low and high PIAS2 expression, respectively. These cells were subjected to invasion, migration, and proliferation assays to evaluate the effects of PIAS2. Changes in genotype, such as epithelial-mesenchymal transition (EMT) markers, were also examined. Additionally, the effect of cigarette smoke condensate (CSC) on PIAS2 expression in oral squamous cell carcinoma (OSCC) cells was investigated. Results: Overexpression of PIAS2 significantly increased the malignant behaviors of oral cancer cells. In YD38 and SAS cells with low PIAS2 expression, overexpression of PIAS2 enhanced proliferation, invasion, and migration. PIAS2 overexpression also affected EMT gene expression, suppressing E-cadherin and increasing fibronectin expression. Conversely, PIAS2 knockdown in OECM1 and SCC25 cells suppressed malignant behaviors and reversed EMT markers, increasing E-cadherin and decreasing fibronectin expression. Furthermore, a dose-dependent increase in PIAS2 expression was observed when OSCC cells were treated with CSC. Conclusion: PIAS2 functions as an oncogene in oral cancer, and cigarette smoking induces PIAS2 expression. Increased PIAS2 levels lead to enhanced malignancy in oral cancer.

Combating air pollution significantly reduced air mercury concentrations in China.

In the past decade, China has motivated proactive emission control measures that have successfully reduced emissions of many air pollutants. For atmospheric mercury, which is a globally transported neurotoxin, much less is known about the long-term changes in its concentrations and anthropogenic emissions in China. In this study, over a decade of continuous observations at four Chinese sites show that gaseous elemental mercury (GEM) concentrations continuously increased until the early 2010s, followed by significant declines at rates of 1.8%-6.1% yr-1 until 2022. The GEM decline from 2013 to 2022 (by 38.6% ± 12.7%) coincided with the decreasing concentrations of criteria air pollutants in China and were larger than those observed elsewhere in the northern hemisphere (5.7%-14.2%). The co-benefits of emission control measures contributed to the reduced anthropogenic Hg emissions and led to the GEM decline in China. We estimated that anthropogenic GEM emissions in China were reduced by 38%-50% (116-151 tons) from 2013 to 2022 using the machine-learning and relationship models.

Paraneoplastic pemphigus associated with nonhuman papillomavirus-related tonsillar squamous cell carcinoma: A case report.

BACKGROUND: Paraneoplastic pemphigus (PNP) is a rare, life-threatening autoimmune bullous disease. Among the ≈500 reported cases of PNP, only 1 case has been associated with tonsillar cancer, specifically, human papillomavirus (HPV)-positive squamous carcinoma. However, the occurrence of PNP in non-HPV-related tonsillar cancer is exceptionally rare and has not been reported to date. METHODS: We present a 58-year-old male with a history of smoking, who experienced recurrent oral ulcers, right neck swelling, and hoarseness for 5 months. Diagnosis of right tonsillar squamous cell carcinoma (cT1N3bM0) was confirmed through computed tomography/magnetic resonance imaging and pathology, not associated with HPV. Histological and immunohistochemical findings indicated PNP. RESULTS: The patient underwent primary tumor resection and ipsilateral neck dissection. Topical steroids and antifungal agents were administered to manage oral lesions and prevent secondary infections. Adjuvant concurrent chemoradiotherapy with cisplatin proceeded smoothly. Postconcurrent chemoradiotherapy follow-up at 3, 6, and 9 months, utilizing computed tomography/magnetic resonance imaging and nasopharyngoscopy, revealed no signs of recurrent cancer or PNP. CONCLUSION: Early indicators, such as oral mucosal ulcers and skin blisters, prompt consideration of underlying oral cancer in PNP. Comprehensive examination is crucial for diagnosing PNP and identifying concurrent internal neoplasms. Effective management includes occult malignancy treatment, postoperative steroid therapy, and infection prevention.

Multimodal Attention Network for Dementia Prediction.

The early identification of an individual's dementia risk is crucial for disease prevention and the design of insurance products in an aging society. This study aims to accurately predict the future incidence risk of dementia in individuals by leveraging the advantages of neural networks. This is, however, complicated by the high dimensionality and sparsity of the International Classification of Diseases (ICD) codes when utilizing data from Taiwan's National Health Insurance, which includes individual profiles and medical records. Inspired by the click-through rate (CTR) problem in recommendation systems, where future user behavior is predicted based on their past consumption records, we address these challenges with a multimodal attention network for dementia (MAND), which incorporates an ICD code embedding layer and multihead self-attention to encode ICD codes and capture interactions among diseases. Additionally, we investigate the applicability of several CTR methods to the dementia prediction problem. MAND achieves an AUC of 0.9010, surpassing traditional CTR models and demonstrating its effectiveness. The highly flexible pipelined design allows for module replacement to meet specific requirements. Furthermore, the analysis of attention scores reveals diseases highly correlated with dementia, aligning with prior research and emphasizing the interpretability of the model. This research deepens our understanding of the diseases associated with dementia, and the accurate prediction provided can serve as an early warning for dementia occurrence, aiding in its prevention.

Natural coral recovery despite negative population growth.

Demographic processes that ensure the recovery and resilience of marine populations are critical as climate change sends an increasing proportion on a trajectory of decline. Yet for some populations, recovery potential remains high. We conducted annual monitoring over 9 years (2012-2020) to assess the recovery of coral populations belonging to the genus Pocillopora. These populations experienced a catastrophic collapse following a severe typhoon in 2009. From the start of the monitoring period, high initial recruitment led to the establishment of a juvenile population that rapidly transitioned to sexually mature adults, which dominated the population within 6 years after the disturbance. As a result, coral cover increased from 1.1% to 20.2% during this time. To identify key demographic drivers of recovery and population growth rates (λ), we applied kernel-resampled integral projection models (IPMs), constructing eight successive models to examine annual change. IPMs were able to capture reproductive traits as key demographic drivers over the initial 3 years, while individual growth was a continuous key demographic driver throughout the entire monitoring period. IPMs further detected a pulse of reproductive output subsequent to two further Category 5 typhoon events during the monitoring period, exemplifying key mechanisms of resilience for coral populations impacted by disturbance. Despite rapid recovery, (i.e., increased coral cover, individual colony growth, low mortality), IPMs estimated predominantly negative values of λ, indicating a declining population. Indeed, while λ translates to a change in the number of individuals, the recovery of coral populations can also be driven by an increase in the size of surviving colonies. Our results illustrate that accumulating long-term data on historical dynamics and applying IPMs to extract demographic drivers are crucial for future predictions that are based on comprehensive and robust understandings of ecological change.

Effectiveness of Voice Therapy on Voice Quality and Function in Individuals with Unilateral Vocal Fold Paralysis: Systematic Review and Meta-Analysis.

BACKGROUND: Unilateral vocal fold paralysis (UVFP), characterized by immobility of one vocal fold, results from injuries of recurrent laryngeal nerves. Voice therapy is a conservative intervention aiming to address these symptoms, but standard protocols are lacking. In this study, we provided an updated review of voice therapy for UVFP over the past 3 years and analyzed the effect of voice therapy from the perspective of voice assessment recommended by the guidelines of the European Laryngological Society and the Union of the European Phoniatricians in 2023. METHODS: Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 statement, we searched the databases, including PubMed, Embase, Web of Science, the Cochrane Library, and SCOPUS, from their earliest records to December 1, 2023. Quality assessment utilized Cochrane Risk of Bias and Risk Of Bias In Non-randomized Studies of Interventions tools. Data extraction encompassed study design, participant characteristics, therapy protocols, and outcome measures, including subjective and objective assessments. We performed heterogeneity analysis by calculating the I2 statistic and meta-analysis by calculating the standardized difference of means and weighted mean differences. RESULTS: Our systematic review and meta-analysis included 12 studies encompassing 459 patients. The review revealed a predominance of female participants across studies. Therapy protocols primarily included breathing control, laryngeal manipulation, and resonance training, often supplemented by home exercises. Outcome measures demonstrated significant improvements in subjective parameter: Voice Handicap Index ((standard mean difference) SMD = -1.51, P < 0.001), acoustic parameters: fundamental frequency (SMD = -0.38, P = 0.003), jitter (SMD = -0.97, P < 0.001), shimmer (SMD = -0.94, P < 0.001), and noise-to-harmonic ratio (SMD = -0.89, P < 0.001), and aerodynamic parameters: maximum phonation time (SMD = 1.29, P < 0.001), with early intervention yielding enhanced rate of complete glottal closure. DISCUSSION: Two randomized controlled trials (RCTs) involved patients aware of their allocation to the treatment group, and the remaining 10 studies were retrospective, leading to bias from deviations in the intended intervention. Subjective and aerodynamic parameter inconsistency was observed, but after excluding studies with the onset of UVFP greater than 12 months, the heterogeneity of VHI scores decreased. The funnel plot was grossly symmetrical in the publication bias test. Significant improvements were noted in subjective, acoustic, and aerodynamic outcomes after intervention. Besides, there were commonalities in protocols, such as breathing control, laryngeal manipulation, and resonance training, often supplemented by home exercises. SYSTEMATIC REVIEW REGISTRATION: This protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on March 28, 2024, registration number: CRD42024529750.

A Convolutional Neural Network with Multifrequency and Structural Similarity Loss Functions for Electromagnetic Imaging.

In this paper, artificial intelligence (AI) technology is applied to the electromagnetic imaging of anisotropic objects. Advances in magnetic anomaly sensing systems and electromagnetic imaging use electromagnetic principles to detect and characterize subsurface or hidden objects. We use measured multifrequency scattered fields to calculate the initial dielectric constant distribution of anisotropic objects through the backpropagation scheme (BPS). Later, the estimated multifrequency permittivity distribution is input to a convolutional neural network (CNN) for the adaptive moment estimation (ADAM) method to reconstruct a more accurate image. In the meantime, we also improve the definition of loss function in the CNN. Numerical results show that the improved loss function unifying the structural similarity index measure (SSIM) and root mean square error (RMSE) can effectively enhance image quality. In our simulation environment, noise interference is considered for both TE (transverse electric) and TM (transverse magnetic) waves to reconstruct anisotropic scatterers. Lastly, we conclude that multifrequency reconstructions are more stable and precise than single-frequency reconstructions.

A topological Hund nodal line antiferromagnet.

The interplay of topology, magnetism, and correlations gives rise to intriguing phases of matter. In this study, through state-of-the-art angle-resolved photoemission spectroscopy, density functional theory, and dynamical mean-field theory calculations, we visualize a fourfold degenerate Dirac nodal line at the boundary of the bulk Brillouin zone in the antiferromagnet YMn2Ge2. We further demonstrate that this gapless, antiferromagnetic Dirac nodal line is enforced by the combination of magnetism, space-time inversion symmetry, and nonsymmorphic lattice symmetry. The corresponding drumhead surface states traverse the whole surface Brillouin zone. YMn2Ge2 thus serves as a platform to exhibit the interplay of multiple degenerate nodal physics and antiferromagnetism. Interestingly, the magnetic nodal line displays a d-orbital dependent renormalization along its trajectory in momentum space, thereby manifesting Hund's coupling. Our findings offer insights into the effect of electronic correlations on magnetic Dirac nodal lines, leading to an antiferromagnetic Hund nodal line.

Effects of aerobic exercise and resistance training on obstructive sleep apnea: a systematic review and meta-analysis.

STUDY OBJECTIVES: We investigated the therapeutic effects of exercise in patients with obstructive sleep apnea (OSA), aiming to identify the subgroups that benefit the most and determine the optimal exercise protocol. METHODS: Major databases were searched for randomized controlled trials involving patients with OSA performing aerobic exercise and/or resistance training. The investigated outcomes included apnea-hypopnea index (AHI), Epworth Sleepiness Scale (ESS), body mass index (BMI), and peak oxygen consumption during exercise (VO2peak). The pre- and postintervention unstandardized mean difference (USMD) of these parameters was compared between the exercise and control groups. RESULTS: Twelve studies involving 526 patients were included. Exercise training significantly reduced AHI (USMD = -7.08 events/hour, 95% confidence interval [CI]: -9.98 to -4.17, p < 0.00001), ESS (USMD = -2.37, CI: -3.21 to -1.54, p < 0.00001), and BMI (USMD = -0.72 kg/m2, CI: -1.22 to -0.22, p = 0.005) and enhanced VO2peak (USMD = 3.46 mL/kg/min, CI: 1.20 to 5.71, p = 0.003). Subgroup analyses revealed that in continuous positive airway pressure (CPAP)-adherent patients, exercise significantly improved VO2peak but did not reduce AHI and ESS. A trend was observed that combining resistance training with aerobic exercise resulted in greater AHI reduction and VO2peak enhancement. Notably, exercise improved AHI, ESS, BMI, and VO2peak regardless of the baseline AHI or BMI. CONCLUSIONS: Exercise, including resistance and aerobic training, should be part of treatment for patients with OSA of all severities, regardless of obesity status, and even for those who are already under CPAP. SYSTEMATIC REVIEW REGISTRATION: The study protocol was registered with the PROSPERO database (#CRD42023423527).

Investigating medication adherence among Taiwanese patient with hypertension, hyperlipidemia, and diabetes: A pilot study using the Chinese version of a Two-Part Medication Nonadherence Scale and the NHI MediCloud system.

BACKGROUND: This pilot study aimed to investigate medication nonadherence among Taiwanese patients with diabetes, hypertension, and hyperlipidemia using the Chinese version of the Two-Part Medication Nonadherence Scale (C-TPMNS) and the National Health Insurance (NHI) Medicloud system. The study revealed insights into the factors contributing to nonadherence and the implications for improving patient adherence to medications for chronic conditions. However, the small sample size limits the generalizability of the findings. Additionally, the study identified the need for further research with larger and more diverse samples to validate the preliminary findings. METHODS: The study conducted surveys individuals in central Taiwan who received three-high medications and those who returned expired medications from chain pharmacies. A structured questionnaire including the C-TPMNS was administered, and additional data on medical history and HbA1c, LDL, and blood pressure levels were collected from the NHI Medicloud system. Data analysis was performed using multiple ordered logistic regression and Wald test methods. Setting interpretation cutoff point to determine medication nonadherence. RESULTS: The study found that 25.8% of participants were non-adherent to prescribed medications. Non-adherent individuals had significantly higher systolic blood pressure (SBP ≥ 140 mmHg) than adherent participants. Non-adherence was also associated with factors such as lower education, single status, living alone, abnormal glucose postprandial concentration, and triglyceride levels. The C-TPMNS demonstrated good reliability (Cronbach's alpha = 0.816) and validity (area under the ROC curve = 0.72). CONCLUSION: The study highlighted the complexity of medication nonadherence with diverse determinants and emphasized the importance of tailored interventions. The findings underscored the need for region-specific research to comprehensively address medication nonadherence, especially focusing on adherence to medications for hypertension, hyperlipidemia, and diabetes. The study also identified the need for larger, more diverse studies to validate and expand upon the initial findings and emphasized the importance of pharmacist interventions and patient empowerment in managing chronic conditions and improving overall health outcomes.

Measurement of Atmospheric Mercury: Current Limitations and Suggestions for Paths Forward.

Mercury (Hg) researchers have made progress in understanding atmospheric Hg, especially with respect to oxidized Hg (HgII) that can represent 2 to 20% of Hg in the atmosphere. Knowledge developed over the past ∼10 years has pointed to existing challenges with current methods for measuring atmospheric Hg concentrations and the chemical composition of HgII compounds. Because of these challenges, atmospheric Hg experts met to discuss limitations of current methods and paths to overcome them considering ongoing research. Major conclusions included that current methods to measure gaseous oxidized and particulate-bound Hg have limitations, and new methods need to be developed to make these measurements more accurate. Developing analytical methods for measurement of HgII chemistry is challenging. While the ultimate goal is the development of ultrasensitive methods for online detection of HgII directly from ambient air, in the meantime, new surfaces are needed on which HgII can be quantitatively collected and from which it can be reversibly desorbed to determine HgII chemistry. Discussion and identification of current limitations, described here, provide a basis for paths forward. Since the atmosphere is the means by which Hg is globally distributed, accurately calibrated measurements are critical to understanding the Hg biogeochemical cycle.

Comparative Efficacy of Various Exercise Therapies and Combined Treatments on Inflammatory Biomarkers and Morphological Measures of Skeletal Muscle among Older Adults with Knee Osteoarthritis: A Network Meta-Analysis.

Osteoarthritis is associated with high risks of sarcopenia in older populations. Exercise interventions are promising treatments for musculoskeletal impairments in knee osteoarthritis (KOA). The purpose of this study was to identify the comparative effects of exercise monotherapy and its adjunct treatments on muscle volume and serum inflammation for older individuals with KOA. A literature search in the electronic databases was comprehensively performed from this study's inception until April 2024 to identify relevant randomized controlled trials (RCTs) that reported muscle morphology and inflammation outcomes after exercise. The included RCTs were analyzed through a frequentist network meta-analysis (NMA). The standard mean difference (SMD) with a 95% confidence interval was estimated for treatment effects on muscle morphology and inflammation biomarkers. The relative effects on each main outcome among all treatment arms were compared using surface under the cumulative ranking (SUCRA) scores. The certainty of evidence (CoE) was assessed by the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) ranking system. Probable moderators of the treatment efficacy were investigated by network meta-regression analysis. This study included 52 RCTs (4255 patients) for NMA. Among the 27 identified treatment arms, isokinetic training plus physical modality as well as low-load resistance training plus blood-flow restriction yielded the most optimal treatment for inflammation reduction (-1.89; SUCRA = 0.97; CoE = high) and muscle hypertrophy (SMD = 1.28; SUCRA = 0.94; CoE = high). The patient's age (ß = -0.73), the intervention time (ß = -0.45), and the follow-up duration (ß = -0.47) were identified as significant determinants of treatment efficacy on muscle hypertrophy. Exercise therapy in combination with noninvasive agents exert additional effects on inflammation reduction and muscle hypertrophy compared to its corresponding monotherapies for the KOA population. However, such treatment efficacy is likely moderated by the patient's age, the intervention time, and the follow-up duration.

Synergistic potential of gellan gum methacrylate and keratin hydrogel for visceral hemostasis and skin tissue regeneration.

In recent years, the development of biodegradable hydrogels as an alternative over the traditional wound dressing has become increasingly significant. These specific hydrogels are able to offer suitable microenvironments to further aid the process of tissue or organ regeneration. However, application of biodegradable hydrogels in clinical medicine remains uncommon due to most biodegradable hydrogels struggle with achieving satisfactory adhesiveness property, high mechanical support and cell compatibility simultaneously. In order to overcome these constraints and enhance the applicability of biodegradable hydrogels, methods have been employed in this study. By reacting gellan gum with methacrylic anhydride and incorporating a biodegradable protein, keratin, we endowed the hydrogels with high pliability via photo-polymerization chain extension, thereby obtaining a biodegradable hydrogel with exceptional properties. Through a series of in vitro tests, GGMA/keratin hydrogels exhibited great cell compatibility via providing an appropriate environment for cell proliferation. Furthermore, this hydrogel not only exhibits extraordinary adhesive ability on visceral tissues but also extends to scenarios involving skin or organ damage, offering valuable assistance in wound healing. Our design provides a suitable platform for cell proliferation and tissue regeneration, which shows prospects for future medical research and clinical applications.

Risk factors for acute kidney injury or mortality and long-term follow-up in coronavirus disease 2019 infected patients in the era before vaccination.

BACKGROUND: Acute kidney injury (AKI) is a severe complication of coronavirus disease 2019 (COVID-19) and is associated with a higher risk of mortality. Understanding the risk factors contributing to COVID-19-related AKI and mortality before vaccination is important for the initiation of preventative measures and early treatment strategies. METHODS: This study included patients aged ≥18 years diagnosed with COVID-19 through polymerase chain reaction from May 2020 to July 2021, admitted in three local hospitals in Taiwan, with an extended follow-up until June 30, 2022. A median follow-up period of 250 days was used to assess AKI development and mortality. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. Multivarible Cox regression analysis of AKI and mortality-related risk factors were performed. RESULTS: Of the 720 hospitalized patients with COVID-19, 90 (22%) developed AKI. Moreover, 80%, 10.1%, and 8.9% of the patients had stage 1, 2, and 3 AKI, respectively. Patients with stage 1 to 3 AKI had significantly lower survival rates than those without AKI ( p = 0.001). The mean duration of post-admission AKI occurrence was 9.50 ± 11.32 days. Older age, hypoalbuminemia, and higher D-dimer and ferritin levels were associated with COVID-19 mortality. In COVID-19 AKI, in addition to older age and high D-dimer and ferritin levels, chronic kidney disease emerged as an independent risk factor. CONCLUSION: COVID-19-related AKI develops early, exhibits a temporal association with respiratory failure, and is linked to an unfavorable prognosis. The mortality rate increased according to the AKI stage ( p = 0.001). Age, albumin, D-dimer, and ferritin levels, and the underlying chronic kidney disease status upon admission are crucial factors for predicting AKI development, which increases the mortality risk. Monitoring the renal function not only within 10 days of COVID-19 onset, but also within 1 month after the disease onset.

Chromosome-level genome assemblies of 2 hemichordates provide new insights into deuterostome origin and chromosome evolution.

Deuterostomes are a monophyletic group of animals that includes Hemichordata, Echinodermata (together called Ambulacraria), and Chordata. The diversity of deuterostome body plans has made it challenging to reconstruct their ancestral condition and to decipher the genetic changes that drove the diversification of deuterostome lineages. Here, we generate chromosome-level genome assemblies of 2 hemichordate species, Ptychodera flava and Schizocardium californicum, and use comparative genomic approaches to infer the chromosomal architecture of the deuterostome common ancestor and delineate lineage-specific chromosomal modifications. We show that hemichordate chromosomes (1N = 23) exhibit remarkable chromosome-scale macrosynteny when compared to other deuterostomes and can be derived from 24 deuterostome ancestral linkage groups (ALGs). These deuterostome ALGs in turn match previously inferred bilaterian ALGs, consistent with a relatively short transition from the last common bilaterian ancestor to the origin of deuterostomes. Based on this deuterostome ALG complement, we deduced chromosomal rearrangement events that occurred in different lineages. For example, a fusion-with-mixing event produced an Ambulacraria-specific ALG that subsequently split into 2 chromosomes in extant hemichordates, while this homologous ALG further fused with another chromosome in sea urchins. Orthologous genes distributed in these rearranged chromosomes are enriched for functions in various developmental processes. We found that the deeply conserved Hox clusters are located in highly rearranged chromosomes and that maintenance of the clusters are likely due to lower densities of transposable elements within the clusters. We also provide evidence that the deuterostome-specific pharyngeal gene cluster was established via the combination of 3 pre-assembled microsyntenic blocks. We suggest that since chromosomal rearrangement events and formation of new gene clusters may change the regulatory controls of developmental genes, these events may have contributed to the evolution of diverse body plans among deuterostomes.

Site-specific thrombus formation: advancements in photothrombosis-on-a-chip technology.

Thrombosis, characterized by blood clot formation within vessels, poses a significant medical challenge. Despite extensive research, the development of effective thrombosis therapies is hindered by substantial costs, lengthy development times, and high failure rates in medication commercialization. Conventional pre-clinical models often oversimplify cardiovascular disease, leading to a disparity between experimental results and human physiological responses. In response, we have engineered a photothrombosis-on-a-chip system. This microfluidic model integrates human endothelium, human whole blood, and blood flow dynamics and employs the photothrombotic method. It enables precise, site-specific thrombus induction through controlled laser irradiation, effectively mimicking both normal and thrombotic physiological conditions on a single chip. Additionally, the system allows for the fine-tuning of thrombus occlusion levels via laser parameter adjustments, offering a flexible thrombus model with varying degrees of obstruction. Additionally, the formation and progression of thrombosis noted on the chip closely resemble the thrombotic conditions observed in mice in previous studies. In the experiments, we perfused recalcified whole blood with Rose Bengal into an endothelialized microchannel and initiated photothrombosis using green laser irradiation. Various imaging methods verified the model's ability to precisely control thrombus formation and occlusion levels. The effectiveness of clinical drugs, including heparin and rt-PA, was assessed, confirming the chip's potential in drug screening applications. In summary, the photothrombosis-on-a-chip system significantly advances human thrombosis modeling. Its precise control over thrombus formation, flexibility in the thrombus severity levels, and capability to simulate dual physiological states on a single platform make it an invaluable tool for targeted drug testing, furthering the development of organ-on-a-chip drug screening techniques.

Targeting TGFß receptor-mediated snail and twist: WSG, a polysaccharide from Ganoderma lucidum, and it-based dissolvable microneedle patch suppress melanoma cells.

Cutaneous melanoma is a lethal skin cancer variant with pronounced aggressiveness and metastatic potential. However, few targeted medications inhibit the progression of melanoma. Ganoderma lucidum, which is a type of mushroom, is widely used as a non-toxic alternative adjunct therapy for cancer patients. This study determines the effect of WSG, which is a water-soluble glucan that is derived from G. lucidum, on melanoma cells. The results show that WSG inhibits cell viability and the mobility of melanoma cells. WSG induces changes in the expression of epithelial-to-mesenchymal transition (EMT)-related markers. WSG also downregulates EMT-related transcription factors, Snail and Twist. Signal transduction assays show that WSG reduces the protein levels in transforming growth factor ß receptors (TGFßRs) and consequently inhibits the phosphorylation of intracellular signaling molecules, such as FAK, ERK1/2 and Smad2. An In vivo study shows that WSG suppresses melanoma growth in B16F10-bearing mice. To enhance transdermal drug delivery and prevent oxidation, two highly biocompatible compounds, polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP), are used to synthesize a dissolvable microneedle patch that is loaded with WSG (MN-WSG). A functional assay shows that MN-WSG has an effect that is comparable to that of WSG alone. These results show that WSG has significant potential as a therapeutic agent for melanoma treatment. MN-WSG may allow groundbreaking therapeutic approaches and offers a novel method for delivering this potent compound effectively.

Elucidating the Role of Let-7d-5p and OLR1 in the Progression and Prognosis of Oral Squamous Cell Carcinoma via FAK/P53 Signaling Axis.

BACKGROUND/AIM: Despite advances in oral squamous cell carcinoma (OSCC) diagnosis and treatment, the five-year survival rate remains low, underscoring the need for improved biomarkers and therapeutic strategies. This study investigated the role of let-7d-5p microRNA (miRNA) and its target gene OLR1 in OSCC, focusing on their implications in tumor progression, metastasis and potential as therapeutic targets. MATERIALS AND METHODS: Employing next-generation sequencing and bioinformatic tools, we profiled differentially expressed miRNAs in metastatic OSCC cell lines, identifying let-7d-5p as a key down-regulated miRNA and OLR1 as a novel target of let-7d-5p. We validated this interaction using luciferase reporter assays and studied the biological effects of modulating let-7d-5p and OLR1 expression on OSCC cell proliferation, migration, invasion, and stemness. Additionally, we analyzed clinical data to establish the relevance of OLR1 expression in OSCC prognosis. RESULTS: Our findings revealed let-7d-5p as a potent suppressor of OSCC metastasis, primarily by targeting and down-regulating OLR1. OLR1-silencing reduced OSCC cell invasiveness, migration, and stemness, indicating its prominent role in tumor progression. Mechanistically, let-7d-5p modulates a signaling cascade involving FAK, SRC, PAXILLIN, and p53, influencing cellular apoptosis and chemoresistance. Clinically, elevated OLR1 expression significantly correlates with advanced OSCC stages and poorer survival rates, highlighting its potential as a prognostic marker and therapeutic target. CONCLUSION: Our study uncovers the significance of the let-7d-5p-OLR1 axis in OSCC pathogenesis, offering novel insights for future therapeutic interventions.

The relationship between oral frailty and oral dysbiosis among hospitalized patients aged older than 50 years.

OBJECTIVE: This study aimed to clarify the relationship between oral frailty and oral dysbiosis among hospitalized patients aged ≥ 50 years. METHODS: A prospective observational study was conducted. Number of teeth, masticatory ability, articulatory oral motor skill, tongue pressure, swallowing pressure, and choking were used to assess oral frailty. Saliva samples were collected from the oral cavity for bacterial culture. RESULTS: A total 103 in patients enrolled and 53.4% suffered from oral frailty. Oral frailty was found to have a 3.07-fold correlation with the presence of Enterobacterales in the oral cavity (p = 0.037), especially in poor articulatory oral motor skill, which showed at greater risk of Enterobacterales isolated from the oral cavity by 5.58-fold (p = 0.01). CONCLUSION: Half of hospitalized patients was found to have oral frailty that was related to more Enterobacterales in the oral cavity. This evidence suggests that the enhancement of articulatory oral motor skills may serve as a potential strategy for mitigating the presence of Enterobacterales within the oral cavity.

Transient Ruddlesden-Popper-Type Defects and Their Influence on Grain Growth and Properties of Lithium Lanthanum Titanate Solid Electrolyte.

Lithium lanthanum titanate (LLTO) perovskite is one of the most promising electrolytes for all-solid-state batteries, but its performance is limited by the presence of grain boundaries (GBs). The fraction of GBs can be significantly reduced by the preparation of coarse-grained LLTO ceramics. In this work, we describe an alternative approach to the fabrication of ceramics with large LLTO grains based on self-seeded grain growth. In compositions with the starting stoichiometry for the Li0.20La0.60TiO3 phase and with a high excess addition of Li (Li:La:Ti = 11:15:25), microstructure development starts with the formation of the layered RP-type Li2La2Ti3O10 phase. Grains with many RP-type defects initially develop into large platelets with thicknesses of up to 10 µm and lengths over 100 µm. Microstructure development continues with the crystallization of LLTO perovskite, epitaxially on the platelets and as smaller grains with thinner in-grain RP-lamellae. Theoretical calculations confirmed that the formation of RP-type sequences is energetically favored and precedes the formation of the LLTO perovskite phase. At around 1250 °C, the RP-type sequences become thermally unstable and gradually recrystallize to LLTO via the ionic exchange between the Li-rich RP-layers and the neighboring Ti and La layers as shown by quantitative HAADF-STEM. At higher sintering temperatures, LLTO grains become free of RP-type defects and the small grains recrystallize onto the large platelike seed grains via Ostwald ripening. The final microstructure is coarse-grained LLTO with total ionic conductivity in the range of 1 × 10-4 S/cm.