Uptake and transport mechanisms for cadmium by Myriophyllum aquaticum in a constructed wetland.

Myriophyllum aquaticum (M. aquaticum), as a Cd-highly enriched and tolerant species, has greater application in phytoremediation of Cd-polluted waters. Mechanisms of Cd uptake and transport of M. aquaticum were comprehensively investigated in this work. Transport direction of Cd was observed both from the roots to the aboveground and vice versa. The aboveground can be harvested during vigorous growth and flowering periods, further improving the efficient phytoremediation of Cd-polluted wastewater. Moreover, analysis of transpiration inhibition, low-temperature treatment and metabolic inhibition indicated that the uptake and transport of Cd by M. aquaticum can be achieved via the coexistence of the free diffusion-dominated apoplast pathway dominated by transpiration and the "cellular pathway" dominated by active absorption, with the active energy-demanding cellular pathway playing a dominant role. The obtained results have important implications in the in-depth exploration of uptake, transport and distribution mechanisms of heavy metals during phytoremediation of aquatic plants.

Association between waist circumference and chronic pain: insights from observational study and two-sample Mendelian randomization.

Background: Current research offers limited clarity on the correlation between waist circumference and chronic pain prevalence. Objective: This investigation seeks to elucidate the potential relationship between waist circumference and chronic pain and their causal association. Methods: An observational study was conducted, leveraging data from the National Health and Nutrition Examination Survey (NHANES) collected between 2001 and 2004. The multivariable logistic regression was used to assess the relationship between waist circumference and chronic pain. Furthermore, a meta-analysis of Mendelian Randomization (MR) was applied to explore a causal relationship between waist circumference and pain. Results: The observational study, post multivariable adjustment, indicated that an increase in waist circumference by 1 dm (decimeter) correlates with a 14% elevation in chronic pain risk (Odds Ratio [OR] = 1.14, 95% Confidence Interval [CI]: 1.04-1.24, p = 0.01). Moreover, the meta-analysis of MR demonstrated that an increased waist circumference was associated with a genetic predisposition to pain risk (OR = 1.14, 95%CI: 1.06-1.23, p = 0.0007). Conclusion: Observational analysis confirmed a significant relationship between increased waist circumference and the incidence of chronic pain, and results based on MR Study identified increased waist circumference as potentially causal for pain.

A Rotating Machinery Fault Diagnosis Method Based on Dynamic Graph Convolution Network and Hard Threshold Denoising.

With the development of precision sensing instruments and data storage devices, the fusion of multi-sensor data in gearbox fault diagnosis has attracted much attention. However, existing methods have difficulty in capturing the local temporal dependencies of multi-sensor monitoring information, and the inescapable noise severely decreases the accuracy of multi-sensor information fusion diagnosis. To address these issues, this paper proposes a fault diagnosis method based on dynamic graph convolutional neural networks and hard threshold denoising. Firstly, considering that the relationships between monitoring data from different sensors change over time, a dynamic graph structure is adopted to model the temporal dependencies of multi-sensor data, and, further, a graph convolutional neural network is constructed to achieve the interaction and feature extraction of temporal information from multi-sensor data. Secondly, to avoid the influence of noise in practical engineering, a hard threshold denoising strategy is designed, and a learnable hard threshold denoising layer is embedded into the graph neural network. Experimental fault datasets from two typical gearbox fault test benches under environmental noise are used to verify the effectiveness of the proposed method in gearbox fault diagnosis. The experimental results show that the proposed DDGCN method achieves an average diagnostic accuracy of up to 99.7% under different levels of environmental noise, demonstrating good noise resistance.

Time-dependent prognostic impact of circumferential resection margin in T3 thoracic esophageal squamous cell carcinoma.

Esophageal cancer presents a clinical challenge due to its high incidence and unfavorable prognosis. The prognostic role of the circumferential resection margin (CRM) remains highly controversial, potentially due to its temporal dynamics coupled with variability in follow-up durations across studies. We aimed to explore the time-dependent prognostic significance of CRM in T3 esophageal squamous cell carcinomas (ESCCs). We systematically reviewed literature from 1990 to 2023 to determine how follow-up duration influences the prognostic role of CRM in esophageal cancer. Concurrently, we performed a retrospective examination of 354 patients who underwent treatment at the National Cancer Center between 2015 and 2018. Integrating a time interaction term in the Cox regression analyses enabled us to not only identify independent risk factors affecting overall survival (OS) but also to specifically scrutinize the potential temporal variations in CRM's prognostic impact. Our literature review suggested that CRM's influence on prognosis diminishes with longer follow-up durations for both classifications, namely the Royal College of Pathologists (RCP) (ß = -0.003, P < 0.001) and the College of American Pathologists (CAP) (ß = -0.007, P < 0.001). Time-dependent multivariate Cox regression analysis emphasized the evolving nature of CRM's prognostic effect, and the inclusion of the time interaction term enhanced model accuracy. In conclusion, CRM is an independent prognostic factor for T3 thoracic ESCC patients. Its influence appears to decrease over extended follow-up periods, shedding light on the heterogeneity seen in previous studies. With the time interaction term, CRM becomes a more precise post-operative prognostic indicator for esophageal cancer.

Comparative efficiency of different polyol-based deep eutectic solvents for chitin extraction from lobster shells.

In this study, deep eutectic solvent (DES) prepared from choline chloride, lactic acid, and one of the four polyols (ethylene glycol, glycerol, xylitol, and sorbitol) were compared and assessed for their effectiveness in extracting chitin from lobster shells. Our results revealed that as the number of hydroxyl groups in polyols increased, the hydrogen bond network within the DESs became denser. However, this led to a corresponding increase in viscosity, which impacted the efficiency of chitin extraction. Among all prepared DESs, choline chloride-lactic acid/glycerol (CCLaGly) exhibited superior extractive ability, resulting in the extraction of pure chitin from lobster shells. The purity, crystallinity, and molecular weight of the extracted chitin using CCLaGly DES were comparable to those of chemically-isolated chitin, with purity reaching 94.76 ± 0.33 %, crystallinity at 78.78 %, and a molecular weight of 655 kDa. Additionally, the physicochemical properties of the DES-extracted chitins were characterized using Fourier-transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, and scanning electron microscopy. This study conducted a comparative analysis of polyol effects on chitin extraction from lobster shells, thereby opening a promising avenue for the utilization of various crustacean shells in sustainable biomaterial production.

Preserving mitochondrial homeostasis protects against drug-induced liver injury via inducing OPTN (optineurin)-dependent Mitophagy.

Disruption of mitochondrial function is observed in multiple drug-induced liver injuries (DILIs), a significant global health threat. However, how the mitochondrial dysfunction occurs and whether maintain mitochondrial homeostasis is beneficial for DILIs remains unclear. Here, we show that defective mitophagy by OPTN (optineurin) ablation causes disrupted mitochondrial homeostasis and aggravates hepatocytes necrosis in DILIs, while OPTN overexpression protects against DILI depending on its mitophagic function. Notably, mass spectrometry analysis identifies a new mitochondrial substrate, GCDH (glutaryl-CoA dehydrogenase), which can be selectively recruited by OPTN for mitophagic degradation, and a new cofactor, VCP (valosin containing protein) that interacts with OPTN to stabilize BECN1 during phagophore assembly, thus boosting OPTN-mediated mitophagy initiation to clear damaged mitochondria and preserve mitochondrial homeostasis in DILIs. Then, the accumulation of OPTN in different DILIs is further validated with a protective effect, and pyridoxine is screened and established to alleviate DILIs by inducing OPTN-mediated mitophagy. Collectively, our findings uncover a dual role of OPTN in mitophagy initiation and implicate the preservation of mitochondrial homeostasis via inducing OPTN-mediated mitophagy as a potential therapeutic approach for DILIs.Abbreviation: AILI: acetaminophen-induced liver injury; ALS: amyotrophic lateral sclerosis; APAP: acetaminophen; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CHX: cycloheximide; Co-IP: co-immunoprecipitation; DILI: drug-induced liver injury; FL: full length; GCDH: glutaryl-CoA dehydrogenase; GOT1/AST: glutamic-oxaloacetic transaminase 1; GO: gene ontology; GSEA: gene set enrichment analysis; GPT/ALT: glutamic - pyruvic transaminase; INH: isoniazid; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MMP: mitochondrial membrane potential; MST: microscale thermophoresis; MT-CO2/COX-II: mitochondrially encoded cytochrome c oxidase II; OPTN: optineurin; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; TIMM23: translocase of inner mitochondrial membrane 23; TOMM20: translocase of outer mitochondrial membrane 20; TSN: toosendanin; VCP: valosin containing protein, WIPI2: WD repeat domain, phosphoinositide interacting 2.

Fluorinated polymer zwitterions on gold nanoparticles: patterned catalyst surfaces guide interfacial transport and electrochemical CO2 reduction.

We report the use of fluorinated polymer zwitterions to build hybrid systems for efficient CO2 electroreduction. The unique combination of hydrophilic phosphorylcholine and hydrophobic fluorinated moieties in these polymers creates a fractal structure with mixed branched cylinders on the surface of gold nanoparticles (AuNPs). In the presence of these polymers, the CO faradaic efficiency improves by 50-80% in the range of -0.7 V to -0.9 V. The fractal structures have a domain size of ∼3 nm, showing enhanced mass transfer kinetics of CO2 approaching the catalyst surfaces without limiting ion diffusion. The phase-separated hydrophilic and hydrophobic domains offer separated channeling to water and CO2, as confirmed by attenuated total reflectance surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS) and molecule dynamic (MD) simulations. H2O molecules permeate extensively into the polymer layer that adsorbs on zwitterions, forming continuous chains, while CO2 molecules strongly associate with the fluorinated tails of fluorinated polyzwitterions, with oxygen facing the positively charged amine groups. Overall, this coupling of zwitterion and fluorocarbon in a polymer material creates new opportunities for defining microenvironments of metallic nanocatalysts in hybrid structures.

Piezo-catalysis Mechanism Elucidation by Tracking Oxygen Reduction to Hydrogen Peroxide with In-situ EPR Spectroscopy.

For piezoelectric catalysis, the catalytic mechanism is a topic of great controversy, with debates centered around whether it belongs to the energy band theory of photocatalysis or the screening charge effect of electrochemical catalysis. Due to the formation of different intermediate active-species during two-electron oxygen reduction reaction (ORR) via electro- and photo-catalysis, the key to solving this problem is precisely monitoring the active species involved in ORR during electro-, photo-, and piezo-catalysis under identical condition. Here, a semiconductor material, BiOBr with abundant oxygen vacancies (BOB-OV) was found remarkable catalytic activity in H2O2 production by all three catalytic methods. By employing in-situ electron paramagnetic resonance (EPR) spectroscopy, the H2O2 evolution pathway through piezo-catalysis over BOB-OV was monitored, which showed a similar reaction pathway to that observed in photo-catalytic process. This finding represents solid evidence supporting the notion that piezo-catalytic mechanism of ORR is more inclined towards photo-catalysis rather than electro-catalysis. Significantly, this exploratory conclusion provides insight to deepen our understanding of piezo-catalysis.

Synergistic regulation of d-band center photocatalytic hydrogen evolution at S-scheme heterojunction reduction sites through defect engineering and interface electric field.

The efficiency of photocatalytic hydrogen evolution can be significantly enhanced while maintaining cost-effectiveness through the synergistic effect of defect surface engineering and multi-component heterojunctions. The structure and properties of NiCo2O4 nanorods were modified by inducing oxygen vacancies at different temperatures in this study, resulting in improved optical properties and electron adsorption capacity. The presence of oxygen vacancies leads to a reduction in the band gap of NiCo2O4, thereby enhancing electron transport efficiency through band gap engineering. Simultaneously, surface properties undergo changes, and vacancy defects serve as electron trapping centers, facilitating an increased participation of electrons in the hydrogen evolution reaction process. The dodecahedron KMP with a cavity structure is additionally introduced to form an S-scheme heterojunction with NiCo2O4. This establishes a novel mechanism for electron transport, which effectively enhances the separation of electron-hole pairs and improves the redox capacity of the photocatalytic system. The adsorption of intermediates in the hydrogen production process is enhanced through synergistic regulation of d-band centers via surface defect engineering and S-scheme heterojunction. Additionally, this approach improves the separation efficiency of electron-hole pairs and accelerates electron transfer dynamics, significantly enhancing hydrogen production efficiency.

Social support mediates social frailty with anxiety and depression.

BACKGROUND: Anxiety and depression are prevalent comorbidities in patients with chronic obstructive pulmonary disease (COPD). However, existing research has yielded conflicting findings regarding the effects of social frailty on anxiety and depression. The primary aim of this study is to validate the relationship between social frailty and social support with anxiety and depression in patients with acute exacerbations of COPD (AECOPD) and to investigate whether social support could explain the variations in prior study outcomes for patients with AECOPD. METHODS: Of the 315 patients hospitalized with AECOPD at the respiratory intensive care unit of a large tertiary care institution in Sichuan Province of China, between August 2022 and June 2023 who were surveyed, 306 were included in the analysis after excluding missing data. We conducted a logistic regression analysis to examine the associations of social frailty and social support with anxiety and depression and performed mediation analyses to examine whether social support mediates the relationship of social frailty with anxiety and depression. RESULTS: The logistic regression analysis revealed that social frailty did not associate anxiety or depression in patients with AECOPD. The mediation analysis supported this idea and indicated that while social frailty does not directly influence anxiety or depression, it can through social support. CONCLUSIONS: The findings suggest that while social frailty may not directly impact anxiety or depression in patients with AECOPD, social support plays a crucial mediating role. Enhancing social support can indirectly alleviate anxiety and depression among these patients. Enhancing social support networks should thus be prioritized by healthcare providers and family members to improve mental health outcomes in this patient population.

Multifunctional phase-change composites for green electromagnetic interference shielding and thermal response prepared under the guidance of an impedance matching strategy.

With the advent of the information age, electromagnetic hazards are becoming more serious. In view of environmental protection, green electromagnetic interference (EMI) shielding materials with little or no secondary reflection have become the ideal choice. In this paper, by freeze-drying, high-temperature carbonization, coating and impregnation backfilling, we prepared carbonized Ni-MOF/reduced graphene oxide/silver nanowire-polyimide@polyethylene glycol composites (Ni@C/r-GO/AgNW-PI@PEG) with gradient conductivity based on impedance matching. The impedance matching layer Ni@C/r-GO-300 reduces the reflection of electromagnetic waves from the surface of the material, the dissipation layer Ni@C/r-GO-600 provides excellent electromagnetic wave dissipation capability, and the reflection layer AgNW-PI ensures that the electromagnetic waves are reflected back into the material. Meanwhile, the EMI shielding performance value of Ni@C/r-GO/AgNW-PI@PEG reaches 62.3 dB with an ultra-low reflectivity (R) of 0.04. In CST simulations, the intrinsic mechanism of electromagnetic energy loss within the material is revealed by energy loss density cloud maps. In addition, heat from high-temperature objects is transferred through the highly thermally conductive AgNW-PI membrane to the long-channel Ni@C/r-GO backbone. Therefore, the composites prepared on the basis of impedance matching will accelerate the use of EMI shielding materials for the thermal management of portable electronic devices and battery heat dissipation packaging.

Down-regulation of microRNA-23a promotes pancreatic ductal adenocarcinoma initiation and progression by up-regulation of FOXM1 expression.

Transcriptional factor Forkhead box M1 (FOXM1) plays an important role in pancreatic ductal adenocarcinoma (PDAC) development and progression. The molecular mechanisms underlying its dysregulation remain unclear. We identified and functionally validated the microRNAs (miRNAs) that critically regulate FOXM1 expression in PDAC. The expression levels of miRNA-23a (miR-23a-3p and -5p) were altered in PDAC cell lines and their effects on FOXM1 signaling and cell proliferation and migration and tumorigenesis were examined in vitro and in vivo using mouse PDAC models. Compared with non-tumor pancreatic tissues, PDAC tissues and cell lines exhibited significantly reduced levels of miR-23a expression. Reduced miR-23a expression and concomitant increase in FOXM1 expression were also observed in acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasia, the major premalignant lesions of PDAC. Transgenic expression of miR-23a reduced the expression of FOXM1 and suppressed cell proliferation and migration in PDAC cells, whereas the inhibitors of miR-23a did the opposite. Loss or reduced levels of miR-23a increased the levels of FOXM1 expression, while increased expression of FOXM1 down-regulated miR-23a expression, suggesting that miR-23a and FOXM1 were mutual negative regulators of their expression in PDAC cells. Therefore, the miR-23a/FOXM1 signaling axis is important in PDAC initiation and progression and could serve as an interventional or therapeutic target for patients with early or late stages of PDAC.

Cancer incidence and mortality in China, 2022.

Background: The National Cancer Center (NCC) of China regularly reports the nationwide statistics on cancer incidence and mortality in China. The International Agency for Research on Cancer (IARC) calculates and publishes the cancer burden of countries around the world every two years. To ensure consistency between the actual surveillance data in China and the data published by IARC, NCC has received approval from the National Health Commission and IARC to simultaneously release the cancer burden data for China in GLOBOCAN 2022. Methods: There were a total of 700 registries reporting high-quality data on cancer incidence and mortality across China in 2018, of which 106 registries with continuous monitoring from 2010 to 2018 were used to establish an age-period-cohort model to simulate the trend of cancer incidence and mortality and to estimate the incidence and mortality in China in 2022. In addition, we analyzed the temporal trends of age-standardized cancer incidence and mortality from 2000 to 2018 using data from 22 continuous cancer registries. Results: It was estimated about 4,824,700 new cancer cases and 2,574,200 new cancer deaths occurred in China in 2022. Cancers of the lung, colon-rectum, thyroid, liver and stomach were the top five cancer types, accounting for 57.42% of new cancer cases. Cancers of the lung, liver, stomach, colon-rectum and esophagus were the five leading causes of cancer deaths, accounting for 67.50% of total cancer deaths. The crude rate and age-standardized incidence rate (ASIR) were 341.75 per 100,000 and 201.61 per 100,000, respectively. The crude mortality rate was 182.34 per 100,000 and the age-standardized mortality rate (ASMR) was 96.47 per 100,000. The ASIR of all cancers combined increased by approximately 1.4% per year during 2000-2018, while the ASMR decreased by approximately 1.3% per year. We observed decreasing trends in ASIR and ASMR for cancers of the esophagus, stomach, and liver, whereas the ASIR increased significantly for cancers of the thyroid, prostate, and cervix. Conclusions: Cancer remains a major public health concern in China, with a cancer profile that reflects the coexistence of developed and developing regions. Sustained implementation of prevention and control measures has resulted in significant reductions in the incidence and mortality rates of certain historically high incidence cancers, such as esophageal, stomach and liver cancers. Adherence to the guidelines of the Healthy China Action Plan and the Cancer Prevention and Control Action Plan, along with continued efforts in comprehensive risk factor control, cancer screening, early diagnosis and treatment, and standardization of diagnostic and therapeutic protocols, are key strategies to effectively mitigate the increasing cancer burden by 2030.

The sparing effect of ultra-high dose rate irradiation on the esophagus.

Background and purpose: Current studies have substantiated the sparing effect of ultra-high dose rate irradiation (FLASH) in various organs including the brain, lungs, and intestines. Whether this sparing effect extends to esophageal tissue remains unexplored. This study aims to compare the different responses of esophageal tissue in histological and protein expression levels following conventional dose rate irradiation (CONV) and FLASH irradiation to ascertain the presence of a sparing effect. Methods and materials: C57 female mice were randomly divided into three groups: control, CONV, and FLASH groups. The chest region of the mice in the radiation groups was exposed to a prescribed dose of 20 Gy using a modified electron linear accelerator. The CONV group received an average dose rate of 0.1 Gy/s, while the FLASH group received an average dose rate of 125 Gy/s. On the 10th day after irradiation, the mice were euthanized and their esophagi were collected for histopathological analysis. Subsequently, label-free proteomic quantification analysis was performed on esophageal tissue. The validation process involved analyzing transmission electron microscopy images and utilizing the parallel reaction monitoring method. Results: Histopathology results indicated a significantly lower extent of esophageal tissue damage in the FLASH group compared to the CONV group (p < 0.05). Label-free quantitative proteomic analysis revealed that the sparing effect observed in the FLASH group may be attributed to a reduction in radiation-induced protein damage associated with mitochondrial functions, including proteins involved in the tricarboxylic acid cycle and oxidative phosphorylation, as well as a decrease in acute inflammatory responses. Conclusions: Compared with CONV irradiation, a sparing effect on esophageal tissue can be observed after FLASH irradiation. This sparing effect is associated with alleviated mitochondria damage and acute inflammation.

Abnormal functional connectivity of the putamen in obsessive-compulsive disorder.

The putamen has been proposed to play a critical role in the development of obsessive-compulsive disorder (OCD). The primary objective of this study was to examine the resting-state regional activity and functional connectivity patterns of the putamen in individuals diagnosed with OCD. To achieve this, we employed resting-state functional magnetic resonance imaging (rs-fMRI) to collect data from a sample of 45 OCD patients and 53 healthy control participants. We aimed to use the regional amplitude of low-frequency fluctuation (ALFF) analysis to generate the ROI masks of the putamen and then conduct the whole brain functional connectivity of the putamen in individuals with OCD. Compared to controls, the OCD group demonstrated decreased ALFF in bilateral putamen. The right putamen also displayed decreased FC with the left putamen extending to the inferior frontal gyrus (IFG), bilateral precuneus extending to calcarine, the right middle occipital cortex extending to the right middle temporal cortex, and the left middle occipital gyrus. The decreased connectivity between the right putamen and the left IFG was negatively correlated with Yale-Brown Obsessive Compulsive scale (Y-BOCS) Obsession Scores. This study aimed to reveal the putamen changes in resting-state activity and connectivity in OCD patients, highlighting the significance of aberrant ALFF/FC of the putamen is a key characteristic of OCD.

Tough and Elastic Cellulose Composite Hydrogels/Films for Flexible Wearable Sensors.

Cellulose and its composites, despite being abundant and sustainable, are typically brittle with very low flexibility/stretchability. This study reports a solution processing method to prepare porous, amorphous, and elastic cellulose hydrogels and films. Native cellulose dissolved in a water-ZnCl2 mixture can form ionic gels through in situ polymerization of acrylic acid (AA) to poly(acrylic acid) (PAA). The addition of up to 30 vol % AA does not change the solubility of cellulose in the water-ZnCl2 mixture. After polymerization, the formation of interpenetrated networks, resulting from the chemical cross-linking of PAA and the ionic/coordination binding among cellulose/PAA and ZnCl2, gives rise to strong, transparent, and ionically conductive hydrogels. These hydrogels can be used for wearable sensors to detect mechanical deformation under stretching, compression, and bending. Upon removal of ZnCl2 and drying the gels, semitransparent amorphous cellulose composite films can be obtained with a Young's modulus of up to 4 GPa. The rehydration of these films leads to the formation of tough, highly elastic composites. With a water content of 3-10.5%, cellulose-containing films as strong as paper also show typical characteristics of elastomers with an elongation of up to 1300%. Such composite films provide an alternative solution to resolving the material sustainability of natural polymers without compromising their mechanical properties.

Diagnostic value of contrast-enhanced ultrasound and shear-wave elastography for small breast nodules.

Background: The study aims to evaluate the diagnostic efficacy of contrast-enhanced ultrasound (CEUS) and shear-wave elastography (SWE) in detecting small malignant breast nodules in an effort to inform further refinements of the Breast Imaging Reporting and Data System (BI-RADS) classification system. Methods: This study retrospectively analyzed patients with breast nodules who underwent conventional ultrasound, CEUS, and SWE at Gongli Hospital from November 2015 to December 2019. The inclusion criteria were nodules ≤ 2 cm in diameter with pathological outcomes determined by biopsy, no prior treatments, and solid or predominantly solid nodules. The exclusion criteria included pregnancy or lactation and low-quality images. Imaging features were detailed and classified per BI-RADS. Diagnostic accuracy was assessed using receiver operating characteristic curves. Results: The study included 302 patients with 305 breast nodules, 113 of which were malignant. The diagnostic accuracy was significantly improved by combining the BI-RADS classification with CEUS and SWE. The combined approach yielded a sensitivity of 88.5%, specificity of 87.0%, positive predictive value of 80.0%, negative predictive value of 92.8%, and accuracy of 87.5% with an area under the curve of 0.877. Notably, 55.8% of BI-RADS 4A nodules were downgraded to BI-RADS 3 and confirmed as benign after pathological examination, suggesting the potential to avoid unnecessary biopsies. Conclusion: The integrated use of the BI-RADS classification, CEUS, and SWE enhances the accuracy of differentiating benign and malignant small breast nodule, potentially reducing the need for unnecessary biopsies.

Piezo1 and Piezo2 channels in retinal ganglion cells and the impact of Piezo1 stimulation on light-dependent neural activity.

Piezo channels are associated with neuropathology in diseases like traumatic brain injury and glaucoma, but pathways linking tissue stretch to aberrant neural signaling remain unclear. The present study demonstrates that Piezo1 activation increases action potential frequency in response to light and the spontaneous dark signal from mouse retinal explants. Piezo1 stimulation was sufficient to increase cytoplasmic Ca 2+ in soma and neurites, while stretch increased spiking activity in current clamp recordings from of isolated retinal ganglion cells (RGCs). Axon-marker beta-tubulin III colocalized with both Piezo1 and Piezo2 protein in the mouse optic nerve head, while RGC nuclear marker BRN3A colocalized with Piezo channels in the soma. Piezo1 was also present on GFAP-positive regions in the optic nerve head and colocalized with glutamine synthetase in the nerve fiber layer, suggesting expression in optic nerve head astrocytes and Müller glia end feet, respectively. Human RGCs from induced pluripotent stem cells also expressed Piezo1 and Piezo2 in soma and axons, while staining patterns in rats resembled those in mice. mRNA message for Piezo1 was greatest in the RPE/choroid tissue, while Piezo2 levels were highest in the optic nerve, with both channels also expressed in the retina. Increased expression of Piezo1 and Piezo2 occurred both 1 and 10 days after a single stretch in vivo; this increase suggests a potential role in rising sensitivity to repeated nerve stretch. In summary, Piezo1 and Piezo2 were detected in the soma and axons of RGCs, and stimulation affected the light-dependent output of RGCs. The rise in RGCs excitability induced by Piezo stimulation may have parallels to the early disease progression in models of glaucoma and other retinal degenerations. Highlights: Activation of Piezo1 excites retinal ganglion cells, paralleling the early neurodegenerative progression in glaucoma mouse models and retinal degeneration.Piezo1 and Piezo2 were expressed in axons and soma of retinal ganglion cells in mice, rats, and human iPSC-RGCs.Functional assays confirmed Piezo1 in soma and neurites of neurons. Sustained elevation of Piezo1 and Piezo2 occurred after a single transient stretch may enhance damage from repeated traumatic nerve injury.

Circulating Tumor DNA Assessment for Treatment Monitoring Adds Value to PSA in Metastatic Castration Resistant Prostate Cancer.

PURPOSE: Enzalutamide after abiraterone progression is commonly used in metastatic castration resistant prostate cancer (mCRPC) despite a low rate of clinical benefit. Analyzing IMbassador250, a phase III trial assessing enzalutamide with or without atezolizumab after abiraterone, we hypothesized that baseline and early changes in circulating tumor DNA (ctDNA) tumor fraction (TF) may identify patients more likely to exhibit survival benefit from enzalutamide. EXPERIMENTAL DESIGN: ctDNA was quantified from plasma samples using a tissue-agnostic assay without buffy coat sequencing. Baseline ctDNA TF, changes in ctDNA TF from baseline to cycle 3 day 1 (C3D1), and detection at C3D1 alone, were compared vs overall response rate (ORR), radiographic progression-free survival (rPFS), median OS (mOS), and 50% reduction in PSA. RESULTS: ctDNA TF detection at baseline and/or C3D1 was associated with shorter rPFS and OS in 494 evaluable patients. Detection of ctDNA TF at C3D1, with or without detection at C1D1, was associated with worse rPFS and mOS than lack of detection. When ctDNA TF and PSA response at C3D1 were discordant, patients with [ctDNA TF undetected/PSA not reduced] had more favorable outcomes than [ctDNA TF detected/PSA reduced] (mOS 22.1 months vs. 16 months, p<0.001). CONCLUSIONS: In a large cohort of mCRPC patients receiving enzalutamide after abiraterone, we demonstrate the utility of a new tissue-agnostic assay for monitoring molecular response based on ctDNA TF detection and dynamics. CtDNA TF provides a minimally-invasive, complementary biomarker to PSA testing and may refine personalized treatment approaches.

The prevalence and effects of sarcopenia in patients with metabolic dysfunction-associated steatotic liver disease (MASLD): A systematic review and meta-analysis.

BACKGROUND AND AIMS: Sarcopenia is a common complication in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, the prevalence and its impact on the survival of sarcopenia in patients with MASLD is unknown. In this study, we aimed to assess the prevalence and effects of sarcopenia in patients with MASLD. METHODS: Systematic review and meta-analysis of full texts of relevant studies were searched from inception until June 12, 2024 in five databases (PubMed, Cochrane Library, Embase, Web of Science, and the China National Knowledge Infrastructure). Next, we assessed the prevalence of sarcopenia in MASLD, and calculated the ORs and HRs between sarcopenia and MASLD based on the adjusted data from individual studies. Statistical analyses were performed using Stata 11.0. RESULTS: Of the 2984 records considered, 29 studies recruiting 63,330 patients were included. The pooled prevalence of sarcopenia in patients with MASLD was 23.5% overall (95% CI; 19.1%-27.9%, I2 = 99.6%), and was higher in Asian patients, male, cross-sectional studies, when BIA were employed to measure muscle mass, one criterion of diagnosis sarcopenia, MASLD was diagnosed employing MRI, and moderate-quality studies. Sarcopenia was associated with MASLD patients (adjusted odds ratio [aOR] 2.08, 95% CI 1.58-2.74, I2 = 93.6%) with similar findings in subgroups stratified by age, study design, methods for measuring muscle mass, assessment method to detect sarcopenia, and study quality. The association between all-cause mortality further supports the association between sarcopenia and poor prognosis with MASLD (aHR 1.59, 95% CI 1.33-1.91, I2 = 0%). CONCLUSIONS: Sarcopenia was strongly associated with MASLD progression and was a risk factor not only for MASLD pathogenesis but was also markedly correlated with MASLD-associated mortality.