Targeted metabolomics study of fatty-acid metabolism in lean metabolic-associated fatty liver disease patients.

BACKGROUND: The annual incidence of metabolic-associated fatty liver disease (MAFLD) in China has been increasing and is often overlooked owing to its insidious characteristics. Approximately 50% of the patients have a normal weight or are not obese. They are said to have lean-type MAFLD, and few studies of such patients are available. Because MAFLD is associated with abnormal lipid metabolism, lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis. AIM: To investigate the serum fatty-acid metabolic characteristics in lean-type MAFLD patients using targeted serum metabolomic technology. METHODS: Between January and June 2022, serum samples were collected from MAFLD patients and healthy individuals who were treated at Shanghai Putuo District Central Hospital for serum metabolomics analysis. Principal component analysis and orthogonal partial least squares-discriminant analysis models were developed, and univariate analysis was used to screen for biomarkers of lean-type MAFLD and analyze metabolic pathways. UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid (PA), oleic acid (OA), linoleic acid (LA), and arachidonic acid (AA) levels in lean-type MAFLD patients. RESULTS: Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.05). Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.01). The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals (P < 0.05) and the expression of triglycerides and fasting blood glucose were increased (P < 0.01). A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P < 0.05 and variable importance in projection > 1". The levels of PA, OA, LA, and AA were significantly increased compared with healthy individuals. CONCLUSION: The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly, yielding 65 identified biomarkers. PA, OA, LA, and AA exhibited the most significant changes, offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.

A pooled analysis of clinical outcome in driver-gene negative non-small cell lung cancer patients with MET overexpression treated with gumarontinib.

Background: MET overexpression represents the most MET aberration in advanced non-small-cell lung cancer (NSCLC). However, except MET exon 14 (METex14) skipping mutation was recognized as a clinical biomarker, the role of MET overexpression as a predictive factor to MET inhibitor is not clear. Objectives: The purpose of the pooled analysis is to explore the safety and efficiency of gumarontinib, a highly selective oral MET inhibitor, in drive-gene negative NSCLC patients with MET overexpression. Design and methods: NSCLC patients with MET overexpression [immunohistochemistry (IHC) ⩾3+ as determined by central laboratory] not carrying epidermal growth factor receptor mutation, METex14 skipping mutation or other known drive gene alternations who received Gumarontinib 300 mg QD from two single arm studies were selected and pooled for the analysis. The efficacy [objective response rate (ORR), disease control rate (DCR), duration of response, progression-free survival (PFS) and overall survival (OS)] and safety [treatment emergent adverse event (TEAE), treatment related AE (TRAE) and serious AE (SAE) were assessed. Results: A total of 32 patients with MET overexpression were included in the analysis, including 12 treatment naïve patients who refused or were unsuitable for chemotherapy, and 20 pre-treated patients who received ⩾1 lines of prior systemic anti-tumour therapies. Overall, the ORR was 37.5% [95% confidence interval (CI): 21.1-56.3%], the DCR was 81.3% (95% CI: 63.6-92.8%), median PFS (mPFS) and median OS (mOS) were 6.9 month (95% CI: 3.6-9.7) and 17.0 month (95% CI: 10.3-not evaluable), respectively. The most common AEs were oedema (59.4%), hypoalbuminaemia (40.6%), alanine aminotransferase increased (31.3%). Conclusion: Gumarontinib showed promising antitumour activity in driver-gene negative locally advanced or metastatic NSCLC patients with MET overexpression, which warranted a further clinical trial. Trial registration: ClinicalTrials.gov identifier: NCT03457532; NCT04270591.

A combination of physiology, metabolomics, and genetics reveals the two-component system ResS/ResR-mediated Fe and Al release from biotite by Pseudomonas pergaminensis F77.

Understanding of the mechanisms on bacteria-regulated mineral dissolution functions is important for further insight into mineral-microbe interactions. The functions of the two-component system have been studied. However, the molecular mechanisms involved in bacterial two-component system-mediated mineral dissolution are poorly understood. Here, the two-component regulatory system ResS/ResR in the mineral-solubilizing bacterium Pseudomonas pergaminensis F77 was characterized for its involvement in biotite dissolution. Strain F77 and the F77ΔresS, F77ΔresR, and F77ΔresS/R mutants were constructed and compared for the ResS/ResR system-mediated Fe and Al release from biotite in the medium and the mechanisms involved. After 3 days of incubation, the F77ΔresS, F77ΔresR, and F77ΔresS/R mutants significantly decreased the Fe and Al concentrations in the medium compared with F77. The F77ΔresS/R mutant had a greater impact on Fe and Al release from biotite than did the F77ΔresS or F77ΔresR mutant. The F77∆resS/R mutant exhibited significantly reduced Fe and Al concentrations by 21-61 % between 12 h and 48 h of incubation compared with F77. Significantly increased pH values and decreased cell counts on the mineral surfaces were found in the presence of the F77∆resS/R mutant compared with those in the presence of F77 between 12 h and 48 h of incubation. Metabolomic analysis revealed that the extracellular metabolites associated with biotite dissolution were downregulated in the F77ΔresS/R mutant. These downregulated metabolites included GDP-fucose, 20-carboxyleukotriene B4, PGP (16:1(9Z)/16:0), 3',5'-cyclic AMP, and a variety of acidic metabolites involved in carbohydrate, amino acid, and lipid metabolisms, glycan biosynthesis, and cellular community function. Furthermore, the expression levels of the genes involved in the production of these metabolites were downregulated in the F77ΔresS/R mutant compared with those in F77. Our findings suggested that the ResS/ResR system in F77 contributed to mineral dissolution by mediating the production of mineral-solubilizing related extracellular metabolites and bacterial adsorption on mineral surface.

Effects of the recovery period after particulate matter pollution events on the dust retention capacity and physiological characteristics of Nerium oleander.

Plants are known for their significant dust retention capacity and are widely used to alleviate atmospheric pollution. Urban green plants are exposed to periodic particulate matter pollution stress, and the time intervals between periods of pollution exposure are often inconsistent. The impact of stress memory and pollution intervals on plant dust retention capacity and physiological characteristics during periodic stress is not yet clear. In this study, the common urban landscaping species Nerium oleander L. was selected as the test plant, and stable isotope (15NH4Cl) tracing technology and aerosol generators were used to simulate periodic PM2.5 pollution. This study included two particulate pollution periods (each lasting 14 days) and one recovery period with three different durations (7, 14, and 21 days). The results indicated that periodic particulate matter pollution-induced stress decreased the dust retention capacity of N. oleander leaf surfaces, but particle adsorption to the wax layer was more stable. As the duration of the recovery period increased, leaf particle absorption, which accounted for the greatest proportion of total dust retention, increased, indicating that leaves are the primary organ for dust retention in Nerium oleander L. Root absorption also increased with increasing recovery periods. Prior pollution stress increased oleander physiological and morphological responses, and the plant's air pollution tolerance significantly improved after a recovery period of >14 days.

Incorporating ReS2 Nanosheet into ZnIn2S4 Nanoflower as Synergistic Z-Scheme Photocatalyst for Highly Effective and Stable Visible-Light-Driven Photocatalytic Hydrogen Evolution and Degradation.

Inspired by natural photosynthesis, the visible-light-driven Z-scheme system is very effective and promising for boosting photocatalytic hydrogen production and pollutant degradation. Here, a synergistic Z-scheme photocatalyst is constructed by coupling ReS2 nanosheet and ZnIn2S4 nanoflower and the experimental evidence for this direct Z-scheme heterostructure is provided by X-ray photoelectron spectroscopy, ultraviolet photoelectron spectroscopy, and electron paramagnetic resonance. Consequently, such a unique nanostructure makes this Z-scheme heterostructure exhibit 23.7 times higher photocatalytic hydrogen production than that of ZnIn2S4 nanoflower. Moreover, the ZnIn2S4/ReS2 photocatalyst is also very stable for photocatalytic hydrogen evolution, almost without activity decay even storing for two weeks. Besides, this Z-scheme heterostructure also exhibits superior photocatalytic degradation rates of methylene blue (1.7 × 10-2 min-1) and mitoxantrone (4.2 × 10-3 min-1) than that of ZnIn2S4 photocatalyst. The ultraviolet-visible absorption spectra, transient photocurrent spectra, open-circuit potential measurement, and electrochemical impedance spectroscopy reveal that the superior photocatalytic performance of ZnIn2S4/ReS2 heterostructure is mostly attributed to its broad and strong visible-light absorption, effective separation of charge carrier, and improved redox ability. This work provides a promising nanostructure design of a visible-light-driven Z-scheme heterostructure to simultaneously promote photocatalytic reduction and oxidation activity.

Chinese quality control indices for standardized diagnosis and treatment of renal cancer (2022 edition).

Renal cancer is one of the most common malignancies of the urinary system, and the number of deaths continues to increase. The standardized management of the diagnosis and treatment of renal cancer is challenging due to the great differences in the diagnosis and treatment of renal cancer in different regions. The Renal Cancer Expert Committee of the National Cancer Quality Control Center (NCQCC) identified a lack of authoritative quality control standards as an opportunity to utilize its multidisciplinary membership to improve the standardized diagnosis and treatment of renal cancer. The Renal Cancer Expert Committee of the NCQCC aims to promote quality control and national standardization, uniformity, and normalization of renal cancer diagnosis and treatment, which ultimately improved the survival rate and quality of life of renal cancer patients. A panel of experts with renal cancer surgery, renal cancer medicine, medical imaging, pathology and radiotherapy were drawn together and determined the quality control standards for the standardized diagnosis and treatment of renal cancer. The Indices includes 20 items that cover all key areas in the diagnosis and treatment of renal cancer, such as standard diagnosis, surgery treatment, systemic treatment, and prognostic evaluation.

Fast, portable and sensitive detection of group B streptococcus DNA using one-pot MIRA-CRISPR system with suboptimal PAM.

The group B Streptococcus (GBS) can generate vertical transmission to infants during delivery, has been seriously threatening the health of infants. Rapid and accurate prenatal GBS diagnosis for pregnant women is a deterministic blueprint to avoid infant viruses. Here, we developed an extraction-free nucleic acid isothermal amplification/CRISPR-Cas12a cutting one-pot system for GBS diagnostic assay by using suboptimal protospacer adjacent motifs, effectively avoiding multiple handling steps and uncapping contamination. The GBS diagnosis assay based on a one-pot system was validated by using fluorescent technique and lateral flow assay strips, exhibited fantastic specificity, accuracy and sensitivity with a limit of detection of 32 copies per reaction (0.64 copies/µL). Moreover, a portable device was constructed and integrated with the one-pot system to realize the GBS detection without professional and scene restrictions, it showed excellent performance in clinical sample detection, which achieved optical and portable GBS detection for point-of-care testing or home-self testing.

Metal-Doping Strategy for Carbon-Based Sonosensitizer in Sonodynamic Therapy of Glioblastoma.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor and known for its challenging prognosis. Sonodynamic therapy (SDT) is an innovative therapeutic approach that shows promise in tumor elimination by activating sonosensitizers with low-intensity ultrasound. In this study, a novel sonosensitizer is synthesized using Cu-doped carbon dots (Cu-CDs) for the sonodynamic treatment of GBM. Doping with copper transforms the carbon dots into a p-n type semiconductor having a bandgap of 1.58 eV, a prolonged lifespan of 10.7 µs, and an improved electron- and hole-separation efficiency. The sonodynamic effect is efficiency enhanced. Western blot analysis reveals that the Cu-CDs induces a biological response leading to cell death, termed as cuproptosis. Specifically, Cu-CDs upregulate dihydrosulfanyl transacetylase expression, thereby establishing a synergistic therapeutic effect against tumor cell death when combined with SDT. Furthermore, Cu-CDs exhibit excellent permeability through the blood-brain barrier and potent anti-tumor activity. Importantly, the Cu-CDs effectively impede the growth of glioblastoma tumors and prolong the survival of mice bearing these tumors. This study provides support for the application of carbon-based nanomaterials as sonosensitizers in tumor therapy.

One-pot conversion of xylose to 1,2-pentanediol catalyzed by an organic acid-assisted Pt/NC in aqueous phase.

The direct synthesis of 1,2-pentanediol (1,2-PeD) from renewable xylose and its derivatives derived from hemicellulose is appealing yet challenging due to its low selectivity for the target product. In this study, one-pot catalytic conversion of xylose to 1,2-PeD was performed by using nitrogen-doped carbon (NC) supported Pt catalysts with the assistance of organic acids. A remarkable yield of 49.3% for 1,2-PeD was achieved by reacting 0.1869 g xylose in 30 mL water at 200 °C under a hydrogen pressure of 3 MPa for 8 h in the presence of 0.1 g of 2.5Pt/NC600 catalyst and 0.1869 g propanoic acid co-catalyst. The presence of vicinal Pt-acid pair sites on the surface of the 2.5Pt/NC600 catalyst exhibited a synergistic effect in promoting the hydrogenation of furfural to furfuryl alcohol intermediate and subsequent hydrogenation and ring-opening reactions leading to the formation of 1,2-PeD. The addition of organic acids, may serve as both acid catalyst for dehydration of xylose and hydrogen donor for hydrogenation of furfural and furfuryl alcohol, thereby promoting the one-pot conversion of xylose to 1,2-PeD. Remarkably, the 2.5Pt/NC600 catalyst demonstrated outstanding catalytic performance and good reusability over five consecutive cycles without significant deactivation.

Wild rodents seed choice is relevant for sustainable agriculture.

Mitigating pre-harvest sprouting (PHS) and post-harvest food loss (PHFL) is essential for enhancing food securrity. To reduce food loss, the use of plant derived specialized metabolites can represent a good approach to develop a more eco-friendly agriculture. Here, we have discovered that soybean seeds hidden underground during winter by Tscherskia triton and Apodemus agrarius during winter possess a higher concentration of volatile organic compounds (VOCs) compared to those remaining exposed in fields. This selection by rodents suggests that among the identified volatiles, 3-FurAldehyde (Fur) and (E)-2-Heptenal (eHep) effectively inhibit the growth of plant pathogens such as Aspergillus flavus, Alternaria alternata, Fusarium solani and Pseudomonas syringae. Additionally, compounds such as Camphene (Cam), 3-FurAldehyde, and (E)-2-Heptenal, suppress the germination of seeds in crops including soybean, rice, maize, and wheat. Importantly, some of these VOCs also prevent rice seeds from pre-harvest sprouting. Consequently, our findings offer straightforward and practical approaches to seed protection and the reduction of PHS and PHFL, indicating potential new pathways for breeding, and reducing both PHS and pesticide usage in agriculture.

[Effects of water-nitrogen interactions on NH3 and N2O emissions and yield in winter wheat cropland]. / 水氮互作对冬小麦农田NH3和N2O排放及产量的影响.

To investigate the effects of different irrigation and nitrogen application modes on nitrogen gaseous loss in winter wheat farmland, we conducted a field experiment at Changqing Irrigation Experiment Station in Shandong Province, with two irrigation levels (80%-90% θf(I1) and 70%-80% θf(I2)) and three nitrogen application levels (conventional nitrogen application of 240 kg·hm-2(N1), nitrogen reduction of 12.5% (N2), and nitrogen reduction of 25% (N3)). The results showed that ammonia volatilization and nitrous oxide emission rate peak appeared within 2-4 days after fertilization or irrigation. The ammonia volatilization rate during the chasing fertilizer period was significantly higher than that during the basal fertilizer period. Compared with other treatments, the ave-rage ammonia volatilization rate of I2N2 treatment during the chasing fertilizer period was reduced by 10.1%-51.6%, and the average nitrous oxide emission rate over the whole growth period was reduced by 15.4%-52.2%. The ammonia volatilization rate was significantly positively associated with surface soil pH value and ammonium nitrogen content, while the nitrous oxide emission rate was significantly positively associated with nitrate content in topsoil. The accumulation amount of soil ammonia volatilization and nitrous oxide emission ranged from 0.83-1.42 and 0.11-0.33 kg·hm-2, respectively. Moderate reduction of irrigation water and nitrogen input could effectively reduce cumulative amounts of ammonia volatilization and nitrous oxide emission from winter wheat farmland. The cumulative amounts of ammonia volatilization and nitrous oxide emission under I1N3 and I2N2 treatments were signi-ficantly lower than those under other treatments. The highest winter wheat yield (5615.6 kg·hm-2) appeared in I2N2 treatment. The irrigation water utilization efficiency of I2 was significantly higher than that of I1, with the maximum increase rate of 45.2%. Compared with N1 and N3 treatments, the maximum increase rate of nitrogen fertilizer productivity and agricultural utilization efficiency in N2 reached 15.2% and 31.8%, respectively. In conclusion, the treatment with 70%-80% θf irrigation level and 210 kg·hm-2 nitrogen input could effectively improve the utilization efficiency of irrigation water and nitrogen fertilization and reduce gaseous loss from winter wheat farmland.

Successful treatment with tislelizumab plus chemotherapy for SMARCA4-deficient undifferentiated tumor: a case report.

SMARCA4-deficient undifferentiated tumor (SMARCA4-dUT) is a devastating subtype of thoracic tumor with SMARCA4 inactivation and is characterized by rapid progression, poor prognosis, and high risk of postoperative recurrence. However, effective treatments for SMARCA4-dUT are lacking. Herein, we describe a patient with SMARCA4-dUT who exhibited an impressive response to the anti-programmed cell death protein-1 (PD-1) antibody (tislelizumab) in combination with conventional chemotherapy (etoposide and cisplatin). To the best of our knowledge, this is the first case of SMARCA4-dUT treated with chemotherapy, comprising etoposide and cisplatin, combined with anti-PD-1 inhibitors. Immunotherapy combined with etoposide and cisplatin may be a promising strategy to treat SMARCA4-dUT.

Trend of Mortality Due to Congenital Anomalies in Children Younger Than 5 Years in Eastern China, 2012-2021: Surveillance Data Analysis.

BACKGROUND: As one of the leading causes of child mortality, deaths due to congenital anomalies (CAs) have been a prominent obstacle to meet Sustainable Development Goal 3.2. OBJECTIVE: We conducted this study to understand the death burden and trend of under-5 CA mortality (CAMR) in Zhejiang, one of the provinces with the best medical services and public health foundations in Eastern China. METHODS: We used data retrieved from the under-5 mortality surveillance system in Zhejiang from 2012 to 2021. CAMR by sex, residence, and age group for each year was calculated and standardized according to 2020 National Population Census sex- and residence-specific live birth data in China. Poisson regression models were used to estimate the annual average change rate (AACR) of CAMR and to obtain the rate ratio between subgroups after adjusting for sex, residence, and age group when appropriate. RESULTS: From 2012 to 2021, a total of 1753 children died from CAs, and the standardized CAMR declined from 121.2 to 62.6 per 100,000 live births with an AACR of -9% (95% CI -10.7% to -7.2%; P<.001). The declining trend was also observed in female and male children, urban and rural children, and neonates and older infants, and the AACRs were -9.7%, -8.5%, -8.5%, -9.2%, -12%, and -6.3%, respectively (all P<.001). However, no significant reduction was observed in children aged 1-4 years (P=.22). Generally, the CAMR rate ratios for male versus female children, rural versus urban children, older infants versus neonates, and older children versus neonates were 1.18 (95% CI 1.08-1.30; P<.001), 1.20 (95% CI 1.08-1.32; P=.001), 0.66 (95% CI 0.59-0.73; P<.001), and 0.20 (95% CI 0.17-0.24; P<.001), respectively. Among all broad CA groups, circulatory system malformations, mainly deaths caused by congenital heart diseases, accounted for 49.4% (866/1753) of deaths and ranked first across all years, although it declined yearly with an AACR of -9.8% (P<.001). Deaths due to chromosomal abnormalities tended to grow in recent years, although the AACR was not significant (P=.90). CONCLUSIONS: CAMR reduced annually, with cardiovascular malformations ranking first across all years in Zhejiang, China. Future research and practices should focus more on the prevention, early detection, long-term management of CAs and comprehensive support for families with children with CAs to improve their survival chances.

Hidden Charge Order and Multiple Electronic Instabilities in EuTe4.

The rare-earth telluride compound EuTe4 exhibits a charge density wave (CDW) and an unconventional thermal hysteresis transition. Herein, we report a comprehensive study of the CDW states in EuTe4 by using low-temperature scanning tunneling microscopy. Two types of charge orders are observed at 4 K, including a newly discovered spindle-shaped pattern and a typical stripe-like pattern. As an exotic charge order, the spindle-shaped CDW is off-axis and barely visible at 77 K, indicating that it is a hidden order developed at low temperature. Based on our first-principles calculations, we reveal the origins of the observed electronic instabilities. The spindle-shaped charge order stems from a subsequent transition based on the stripe-like CDW phase. Our work demonstrates that the competition and cooperation between multiple charge orders can generate exotic quantum phases.

Robust arterial compliance estimation with Katz's fractal dimension of photoplethysmography.

Arterial compliance (AC) plays a crucial role in vascular aging and cardiovascular disease. The ability to continuously estimate aortic AC or its surrogate, pulse pressure (PP), through wearable devices is highly desirable, given its strong association with daily activities. While the single-site photoplethysmography (PPG)-derived arterial stiffness indices show reasonable correlations with AC, they are susceptible to noise interference, limiting their practical use. To overcome this challenge, our study introduces a noise-resistant indicator of AC: Katz's fractal dimension (KFD) of PPG signals. We showed that KFD integrated the signal complexity arising from compliance changes across a cardiac cycle and vascular structural complexity, thereby decreasing its dependence on individual characteristic points. To assess its capability in measuring AC, we conducted a comprehensive evaluation using both in silico studies with 4374 virtual human data and real-world measurements. In the virtual human studies, KFD demonstrated a strong correlation with AC (r = 0.75), which only experienced a slight decrease to 0.66 at a signal-to-noise ratio of 15dB, surpassing the best PPG-morphology-derived AC measure (r = 0.41) under the same noise condition. In addition, we observed that KFD's sensitivity to AC varied based on the individual's hemodynamic status, which may further enhance the accuracy of AC estimations. These in silico findings were supported by real-world measurements encompassing diverse health conditions. In conclusion, our study suggests that PPG-derived KFD has the potential to continuously and reliably monitor arterial compliance, enabling unobtrusive and wearable assessment of cardiovascular health.

A systematic review of transcranial magnetic stimulation treatment for autism spectrum disorder.

Autism spectrum disorder (ASD) is a behaviorally defined complex neurodevelopmental syndrome characterized by persistent social communication and interaction deficit. Transcranial magnetic stimulation (TMS) is a promising and emerging tool for the intervention of ASD by reducing both core and associate symptoms. Several reviews have been published regarding TMS-based ASD treatment, however, a systematic review on study characteristics, specific stimulating parameters, localization techniques, stimulated targets, behavioral outcomes, and neuroimage biomarker changes is lagged behind since 2018. Here, we performed a systematic search on literatures published after 2018 in PubMed, Web of Science, and Science Direct. After screening, the final systematic review included 17 articles, composing seven randomized controlled trial studies and ten open-label studies. Two studies are double-blind, while the other studies have a moderate to high risk of bias attributing to inadequate subject- and evaluator-blinding to treatment allocation. Five studies utilize theta-burst stimulation mode, and the others apply repetitive TMS with low frequency (five studies), high frequency (six studies), and combined low and high frequency stimulation (one study). Most researchers prioritize the bilateral dorsolateral prefrontal lobe as stimulation target, while parietal lobule, inferior parietal lobule, and posterior superior temporal sulci have also emerged as new targets of attention. One third of the studies use neuronavigation based on anatomical magnetic resonance imaging to locate the stimulation target. After TMS intervention, discernible enhancements across a spectrum of scales are evident in stereotyped behavior, repetitive behavior, and verbal social domains. A comprehensive review of literature spanning the last five years demonstrates the potential of TMS treatment for ASD in ameliorating the clinical core symptoms.

Proteomic profile of tissue-derived extracellular vesicles from benign odontogenic lesions.

BACKGROUND: Benign odontogenic lesions (BOLs) can cause severe jaw bone defects and compromise the quality of life of patients. Extracellular vesicles (EVs) are well-established and versatile players in mediating pathophysiological events. EVs in the interstitial space (tissue-derived EVs or Ti-EVs) possess higher specificity and sensitivity in disease-related biomarker discovery. However, the role of Ti-EV-loaded proteins in mediating the development of BOLs has remained untapped. Herein, we aim to explore the contribution of Ti-EV-loaded proteins to the development of BOLs. METHODS: Samples were obtained from 3 with dental follicle, 3 with dentigerous cyst (DC), 7 with odontogenic keratocyst (OKC), and 3 patients with ameloblastoma (AM). Tissue-derived EVs were then extracted, purified, and validated using ultracentrifugation, transmission electron microscopy, and western blotting. Proteins from Ti-EVs were analyzed using LC-ESI tandem mass spectroscopy and differentially expressed proteins were screened, which was then validated by immunohistochemistry and immunofluorescence assays. RESULTS: The protein profile of Ti-EVs in each group was mapped by LC-MS analysis. The top 10 abundant proteins in BOL-derived Ti-EVs were COL6A3, COL6A1, ALB, HIST1H4A, HBB, ACTB, HIST1H2BD, ANXA2, COL6A2 and FBN1. Additionally, unique proteins in the Ti-EVs from various lesions were identified. Moreover, focal adhesion kinase (FAK) and myeloid differentiation primary response 88 (MyD88) showed higher expressions in Ti-EVs derived from OKC and AM, which were confirmed by immunohistochemistry and immunofluorescence staining. CONCLUSIONS: Ti-EVs containing FAK and MyD88 might be related to the development of OKC and AM, which can be potential therapeutic targets.

Analysis of the acoustoelectric response of SAW gas sensors using a COM model.

Surface acoustic wave (SAW) gas sensors based on the acoustoelectric effect exhibit wide application prospects for in situ gas detection. However, establishing accurate models for calculating the scattering parameters of SAW gas sensors remains a challenge. Here, we present a coupling of modes (COM) model that includes the acoustoelectric effect and specifically explains the nonmonotonic variation in the center frequency with respect to the sensing film's sheet conductivity. Several sensing parameters of the gas sensors, including the center frequency, insertion loss, and phase, were experimentally compared for accuracy and practicality. Finally, the frequency of the phase extremum (FPE) shift was determined to vary monotonically, and the range of selectable test points was wide, making the FPE an appropriate response parameter for leveraging in SAW gas sensors. The simulation results of the COM model were highly consistent with the experimental results. Our study is proposed to provide theoretical guidance for the future development of gas SAW sensors.

A fundamental study on postmortem submersion interval estimation by metabolomics analyzing of gastrocnemius muscle from submersed rat models in freshwater.

In forensic practice, determining the postmortem submersion interval (PMSI) and cause-of-death of cadavers in aquatic ecosystems has always been challenging task. Traditional approaches are not yet able to address these issues effectively and adequately. Our previous study proposed novel models to predict the PMSI and cause-of-death based on metabolites of blood from rats immersed in freshwater. However, with the advance of putrefaction, it is hardly to obtain blood samples beyond 3 days postmortem. To further assess the feasibility of PMSI estimation and drowning diagnosis in the later postmortem phase, gastrocnemius, the more degradation-resistant tissue, was collected from drowned rats and postmortem submersion model in freshwater immediately after death, and at 1 day, 3 days, 5 days, 7 days, and 10 days postmortem respectively. Then the samples were analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to investigate the dynamic changes of the metabolites. A total of 924 metabolites were identified. Similar chronological changes of gastrocnemius metabolites were observed in the drowning and postmortem submersion groups. The difference in metabolic profiles between drowning and postmortem submersion groups was only evident in the initial 1 day postmortem, which was faded as the PMSI extension. Nineteen metabolites representing temporally-dynamic patterns were selected as biomarkers for PMSI estimation. A regression model was built based on these biomarkers with random forest algorithm, which yielded a mean absolute error (± SE) of 5.856 (± 1.296) h on validation samples from an independent experiment. These findings added to our knowledge of chronological changes in muscle metabolites from submerged vertebrate remains during decomposition, which provided a new perspective for PMSI estimation.

Impact of wildfire ash on skin and gut microbiomes and survival of Rana dybowskii.

Climate change and human activities escalate the frequency and intensity of wildfires, threatening amphibian habitats and survival; yet, research on these impacts remains limited. Wildfire ash alters water quality, introduces contaminants, and may disrupt microbial communities, impacting gut and skin microbiota; however, the effects on gut and skin microbiota remain unclear. Rana dybowskii were exposed to five concentrations (0 g L-1, 1.25 g L-1, 2.5 g L-1, 5 g L-1, and 10 g L-1) of aqueous extracts of wildfire ashes (AEAs) for 30 days to assess AEAs' metal content, survival, and microbiota diversity via Illumina sequencing. Our results showed that the major elements in ash were Ca > K > Mg > Al > Fe > Na > Mn, while in AEA they were K > Ca > Na > Mg > As > Al > Cu. A significant decrease in amphibian survival rates with increased AEA concentration was shown. The beta diversity analysis revealed distinct shifts in microbiota composition. Notably, bacterial genera associated with potential health risks showed increased abundance in skin microbiota, emphasising the potential for ash exposure to affect amphibian health. Functional prediction analyses revealed significant shifts in metabolic pathways related to health and disease, indicating that wildfire ash exposure may influence amphibian health through changes in microbial functions. This study highlights the urgent need for strategies to mitigate wildfire ash impacts on amphibians, as it significantly alters microbiota and affects their survival and health.