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Slave Province in Canada is an Archean granite–supracrustal terrane at the northwestern corner of the Canadian Shield. It is bordered by the Thelon–Taltson orogen (2.0 to 1.9 Ga) to the southeast and the Wopmay orogen (1.9 to 1.8 Ga) to the west. Acasta gneisses, exposed in the westernmost Slave Province, and the Wopmay rocks, located close to the gneisses, were systematically collected for K–Ar and laser step-heating 40Ar/39Ar single-crystal analyses of the biotite and amphibole. The K–Ar biotite ages of the four Wopmay samples range from 1816 ± 18 Ma to 1854 ± 26 Ma. The 40Ar/39Ar biotite analyses of the three Wopmay samples yield plateau ages of 1826 ± 21 Ma, 1886 ± 13 Ma, and 1870 ± 18 Ma. These ages fall within the reported U–Pb zircon age range of the Wopmay orogen. The K–Ar biotite ages of the fifteen Acasta gneisses range from 1779 ± 25 Ma to 1877 ± 26 Ma, except for one younger sample (1711 ± 25 Ma). The 40Ar/39Ar analyses of the biotite crystals from three samples give the plateau ages of 1877 ± 8 Ma, 1935 ± 14 Ma, and 1951 ± 11 Ma. The K–Ar amphibole ages from twelve samples range from 1949 ± 19 Ma to 1685 ± 25 Ma. Two samples of them give ages older than the zircon U-Pb age of Hepburn plutons. The 40Ar/39Ar analyses of the amphibole crystals show varied age relations. The two samples give plateau ages of 1814 ± 22 Ma and 1964 ± 12 Ma. Some samples exhibit apparent old ages of ~2000 Ma in the middle temperature fractions. These old fractions result from the amphibole crystals, originally formed in the Archean, being affected by the thermal events during the Wopmay orogeny but not fully resetting. These observations suggest that the K–Ar system ages of the biotite and amphibole in the Archean Acasta gneiss were rejuvenated during the Paleoproterozoic ages. The Discussion explores the possibility that the heat source rejuvenating the K–Ar system ages may have arisen due to asthenospheric extrusion into the wedge mantle, a process likely triggered by subduction rollback. [ABSTRACT FROM AUTHOR]

Gender Medicine has had an enormous expansion over the last ten years. Autoimmune liver diseases include several conditions, i.e., autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and conditions involving the liver or biliary tree overlapping with AIH, as well as IgG4-related disease. However, little is known about the impact of sex in the pathogenesis and natural history of these conditions. The purpose of this review is to provide an update of the gender disparities among the autoimmune liver diseases by reviewing the data published from 1999 to 2023. The epidemiology of these diseases has been changing over the last years, due to the amelioration of knowledge in their diagnosis, pathogenesis, and treatment. The clinical data collected so far support the existence of sex differences in the natural history of autoimmune liver diseases. Notably, their history could be longer than that which is now known, with problems being initiated even at a pediatric age. Moreover, gender disparity has been observed during the onset of complications related to end-stage liver disease, including cancer incidence. However, there is still an important debate among researchers about the impact of sex and the pathogenesis of these conditions. With this review, we would like to emphasize the urgency of basic science and clinical research to increase our understanding of the sex differences in autoimmune liver diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Bladder cancer is a common disease in urological patients. The approach to treatment depends on the severity of the tumor; in this article, we focus on tumors that do not invade the muscle layer of the bladder. Those tumors are resected during an endoscopic procedure (TURBT), but often reoccur. Treating bladder cancer with drugs instead of surgical removal of the bladder (radical cystectomy) is paramount for patients quality of life and overall well-being. The aim of this paper is to review methods of conservative treatment of tumors unresponsive to the typical treatment of choice (BCG instillations). Bladder cancer is the 10th most popular cancer in the world, and non-muscle-invasive bladder cancer (NMIBC) is diagnosed in ~80% of all cases. Treatments for NMIBC include transurethral resection of the bladder tumor (TURBT) and intravesical instillations of Bacillus Calmette-Guérin (BCG). Treatment of BCG-unresponsive tumors is scarce and usually leads to Radical Cystectomy. In this paper, we review recent advancements in conservative treatment of BCG-unresponsive tumors. The main focus of the paper is FDA-approved medications: Pembrolizumab and Nadofaragene Firadenovec (Adstiladrin). Other, less researched therapeutic possibilities are also included, namely: N-803 immunotherapy, TAR-200 and TAR-210 intravesical delivery systems and combined Cabazitaxel, Gemcitabine and Cisplatin chemotherapy. Conservative treatment and delaying radical cystectomy would greatly benefit patients' quality of life; it is undoubtedly the future of BCG-unresponsive NMIBC. [ABSTRACT FROM AUTHOR]

Alternating current can result in flickering—or pulsing—in the brightness of light emitted by luminaires. Lighting flicker typically occurs in the range of 100 to 140 cycles per second (Hz), which is too fast for visual perception by most organisms. However, evidence indicates that many organisms perceive flicker with non-visual photoreceptors present on the retinas. Exposure to flickering lights at night disrupts the circadian rhythm of organisms, leading to symptoms similar to blue light exposure at night. The traditional method for detecting flickering is with a flickermeter held near a single light. In this paper, we explore the use of high-speed camera data in the collection of temporal profiles for groups of luminaires simultaneously at distances ranging from several meters to several kilometers. Temporal profiles are extracted for individual lighting features and the full scene. The identification of luminaire types is based on their spectral signatures. With the camera data, it is possible to identify flickering and non-flickering lights, to determine the flicker frequency, to calculate percent flicker and the flicker index, and to identify groups of lights whose flickers are synchronized. Both flickering and non-flickering luminaires can be found for LED, metal halide, fluorescent, and compact fluorescent lights. To date, flickering has been detected in all of the incandescent, high-pressure sodium, and low-pressure sodium luminaires that we measured. We found that flicker synchronization is often present for lights installed within a single facility and also for strings of streetlights. We also found that flicker exposure can come from the light reflected off of the earth's surface. Luminaires designed to illuminate large areas often saturate high-speed camera data collection. This saturation can be reduced or eliminated using neutral density filters on the camera. Published experimental data on the impacts of flicker on organisms remains sparse. Many studies have drawn inferences on the impacts of spectral and lighting brightness on organisms without controlling for flicker. Our conclusion is that lighting flicker is a type of light pollution. The use of high-speed camera data makes it easier to include flicker as a variable in studies regarding the impacts of lighting on organisms. [ABSTRACT FROM AUTHOR]

In this study, we investigated the fatty acid composition and anticancer activity of neutral and polar lipid fractions extracted from Crassostrea gigas oysters cultured in Nha Phu Lagoon, Khanh Hoa Coast, harvested during the five months of January, April, May, September, and November. Analysis revealed that saturated fatty acids (SFAs) were the most abundant fatty acids in the neutral lipid fraction, followed by monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs). Conversely, the polar lipid fraction exhibited a different order, with PUFAs being the most abundant, followed by MUFAs and SFAs. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were identified as the most prevalent polyunsaturated fatty acids, while oleic acid and palmitic acid were the predominant monounsaturated and saturated fatty acids, respectively. Notably, the combined content of EPA and DHA in the polar lipid fraction consistently exceeded 30% throughout all five months of analysis. Thrombogenicity index (TI) values ranged from 0.13 to 0.29 for the polar lipid fraction and from 0.6 to 1.1 for the neutral lipid fraction. Moreover, the polar lipid fraction exhibited significantly higher n3/n6 ratios compared to the neutral lipid fraction. The polar lipid fraction exhibited stronger inhibitory effects on the growth of the three cancer cell lines (HepG2, MDA-MB-231, and RD) compared to the neutral lipid fraction. The findings of the present study show that lipids extracted from C. gigas oysters cultured in Khanh Hoa Coast have a weak anticancer activity but may still aid in prevention and treatment of certain cancer types. [ABSTRACT FROM AUTHOR]

The transition from a comorbidity-based to a multimorbidity-focused to ultimately a network medicine approach in people with rheumatic diseases might mark a significant shift in how we understand and manage these complex conditions. Multimorbidity expands on the concept of comorbidity by encompassing the presence of multiple diseases, which results in further individual and societal impacts. This approach, while valuable, often leads to fragmented care focused on individual diseases rather than the patient as a whole.Network medicine, on the other hand, offers a more integrated perspective. It is an emerging concept that leverages the understanding of biologic networks and their interactions within the human body to gain insights into disease mechanisms. In the context of rheumatic diseases, network medicine involves examining how different diseases interconnect and influence each other through shared pathways, genetic factors, and molecular mechanisms.This paradigm shift allows for a more holistic understanding in how we manage rheumatic diseases. For instance, rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus are not just a collection of symptoms affecting various organs but are also interconnected through underlying systemic inflammatory processes, immune system dysregulation, and genetic predispositions., Competing Interests: Declarations. Conflict of Interest: Winston Gilcrease, Luca Manfredi, Savino Sciascia, and Fulvio Ricceri have nothing to disclose. Ethical Approval: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors., (© 2024. The Author(s).)

Background: Macroscopic vascular invasion (MVI) significantly impacts survival in patients with hepatocellular carcinoma (HCC), warranting systemic therapy over locoregional therapy. Despite novel approaches, HCC with MVI has a poor prognosis compared to early-to intermediate-stage HCC. This study aimed to evaluate the safety and efficacy of carbon-ion radiotherapy (C-ion RT) for HCC characterized by MVI. Methods: This retrospective cohort study evaluated HCC patients with MVI treated using C-ion RT with a dose of 45.0–48.0 Gy/2 fractions or 52.8–60.0 Gy/4 fractions between 1995 and 2020 at our institution in Japan. We analyzed the prognostic factors and rates of local recurrence, survival, and adverse events. The local recurrence rate was determined using the cumulative incidence function, with death as a competing event. Survival rates were determined using the Kaplan–Meier method. The log-rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis were used to compare subgroups. Results: In total, 76 patients with a median age of 71 years (range, 45–86 years) were evaluated. Among them, 68 had Child–Pugh grade A while eight had grade B disease. In 17 patients, the vascular tumor thrombus reached the inferior vena cava or main trunk of the portal vein. Over a median follow-up period of 27.9 months (range, 1.5–180.4 months), the 2-year overall survival, progression-free survival, and local recurrence rates were 70.0% (95% confidence interval [CI]: 57.7–79.4%), 32.7% (95% CI: 22.0–43.8%), and 8.9% (95% CI: 1.7–23.5%), respectively. A naïve tumor and a single lesion were significant prognostic factors for overall survival in the univariate analysis. Albumin-bilirubin grade 1 and a single lesion were independent prognostic factors in the multivariate analysis. Overall, four patients (5%) experienced grade 3 late adverse events, with no observed grade 4 or 5 acute or late adverse events. Conclusions: C-ion RT for HCC with MVI showed favorable local control and survival benefits with minimal toxicity. [ABSTRACT FROM AUTHOR]

Highlights: Recent advances and design strategies for molecular machines working as collectives in building smart responsive materials and micro/nanoscale operations are summarized in this review. The modulation of collective behaviors characteristics and properties is summarized in focus, including reversibility, amplification, anisotropy and reconfigurability of smart materials, as well as reconfigurability, orthogonality and logical control of swarming. Experiences and paradigms in the field of micro/nanorobotics in collective construction, control strategies, and model transformations are expected to provide guidance for molecular machines to build reconfigurable, multi-dimensional, and multi-modularity advanced collectives. Molecular machines are key to cellular activity where they are involved in converting chemical and light energy into efficient mechanical work. During the last 60 years, designing molecular structures capable of generating unidirectional mechanical motion at the nanoscale has been the topic of intense research. Effective progress has been made, attributed to advances in various fields such as supramolecular chemistry, biology and nanotechnology, and informatics. However, individual molecular machines are only capable of producing nanometer work and generally have only a single functionality. In order to address these problems, collective behaviors realized by integrating several or more of these individual mechanical units in space and time have become a new paradigm. In this review, we comprehensively discuss recent developments in the collective behaviors of molecular machines. In particular, collective behavior is divided into two paradigms. One is the appropriate integration of molecular machines to efficiently amplify molecular motions and deformations to construct novel functional materials. The other is the construction of swarming modes at the supramolecular level to perform nanoscale or microscale operations. We discuss design strategies for both modes and focus on the modulation of features and properties. Subsequently, in order to address existing challenges, the idea of transferring experience gained in the field of micro/nano robotics is presented, offering prospects for future developments in the collective behavior of molecular machines. [ABSTRACT FROM AUTHOR]

G-quadruplexes or G4s are non-canonical secondary structures of nucleic acids characterized by guanines arranged in stacked tetraplex arrays. Decades of research into these peculiar assemblies of DNA and RNA, fueled by the development and optimization of a vast array of techniques and assays, has resulted in a large amount of information regarding their structure, stability, localization, and biological significance in native systems. A plethora of articles have reported the roles of G-quadruplexes in multiple pathways across several species, ranging from gene expression regulation to RNA biogenesis and trafficking, DNA replication, and genome maintenance. Crucially, a large amount of experimental evidence has highlighted the roles of G-quadruplexes in cancer biology and other pathologies, pointing at these structurally unique guanine assemblies as amenable drug targets. Given the rapid expansion of this field of research, this review aims at summarizing all the relevant aspects of G-quadruplex biology by combining and discussing results from seminal works as well as more recent and cutting-edge experimental evidence. Additionally, the most common methodologies used to study G4s are presented to aid the reader in critically interpreting and integrating experimental data. [ABSTRACT FROM AUTHOR]

Simple Summary: Sarcopenia, conceived as low skeletal muscle mass and function, has been associated with worse outcomes in patients treated with Sorafenib for advanced HCC, with data coming mainly from the Oriental series. Skeletal muscle mass can be easily quantified from abdominal CT scans performed for advanced HCC staging. Sarcopenia and impaired liver function (MELD > 9) are strong predictors of unfavorable outcomes in patients affected by advanced HCC treated with Sorafenib. Their copresence can identify a subset of patients with particularly bad prognoses. Background and aims: Sarcopenia has been associated with poor outcomes in patients with cirrhosis and hepatocellular carcinoma. We investigated the impact of sarcopenia on survival in patients with advanced hepatocellular carcinoma treated with Sorafenib. Methods: A total of 328 patients were retrospectively analyzed. All patients had an abdominal CT scan within 8 weeks prior to the start of treatment. Two cohorts of patients were analyzed: the "Training Group" (215 patients) and the "Validation Group" (113 patients). Sarcopenia was defined by reduced skeletal muscle index, calculated from an L3 section CT image. Results: Sarcopenia was present in 48% of the training group and 50% of the validation group. At multivariate analysis, sarcopenia (HR: 1.47, p = 0.026 in training; HR 1.99, p = 0.033 in validation) and MELD > 9 (HR: 1.37, p = 0.037 in training; HR 1.78, p = 0.035 in validation) emerged as independent prognostic factors in both groups. We assembled a prognostic indicator named "SARCO-MELD" based on the two independent prognostic factors, creating three groups: group 1 (0 prognostic factors), group 2 (1 factor) and group 3 (2 factors), the latter with significantly worse survival and shorter time receiving treatment. [ABSTRACT FROM AUTHOR]

Background: Tongue diagnosis in traditional Chinese medicine (TCM) provides clinically important, objective evidence from direct observation of specific features that assist with diagnosis. However, the current interpretation of tongue features requires a significant amount of manpower and time. TCM physicians may have different interpretations of features displayed by the same tongue. An automated interpretation system that interprets tongue features would expedite the interpretation process and yield more consistent results. Materials and methods: This study applied deep learning visualization to tongue diagnosis. After collecting tongue images and corresponding interpretation reports by TCM physicians in a single teaching hospital, various tongue features such as fissures, tooth marks, and different types of coatings were annotated manually with rectangles. These annotated data and images were used to train a deep learning object detection model. Upon completion of training, the position of each tongue feature was dynamically marked. Results: A large high-quality manually annotated tongue feature dataset was constructed and analyzed. A detection model was trained with average precision (AP) 47.67%, 58.94%, 71.25% and 59.78% for fissures, tooth marks, thick and yellow coatings, respectively. At over 40 frames per second on a NVIDIA GeForce GTX 1060, the model was capable of detecting tongue features from any viewpoint in real time. Conclusions/Significance: This study constructed a tongue feature dataset and trained a deep learning object detection model to locate tongue features in real time. The model provided interpretability and intuitiveness that are often lacking in general neural network models and implies good feasibility for clinical application. [ABSTRACT FROM AUTHOR]

The textile industry is known for its excessive water consumption and environmental impact. One of the major challenges it faces is managing pollution generated by dyes, particularly bifunctional dyes, such as sumireact supra yellow s-hbu, with a red appearance and sumifix supra lemon-yellow e-xf, with a yellow appearance. This study aimed to investigate the decolorization kinetics of synthetic solutions of said bifunctional dyes, which comprise triazine and vinylsulfon. We conducted various tests, including modifications of pH, the addition of TiO2 P-50 nanoparticles, exposure to solar radiation, limited contact with oxygen, and eolic agitation. The initial solutions had a concentration of 1000 ppm of textile dye. The study showed that the reaction order for the "red" solutions in the R6 and R9 reactors and all the yellow solutions was ½. The concentration of nanoparticles and pH had a significant impact on the reaction rate. The yellow solutions with a concentration of 800 ppm and pH levels of 3.15, 4.13, and 2.25 demonstrated 100% color discoloration, followed by solutions with a concentration of 400 ppm and pH levels of 3.15, 2.25, and 4.13. The analysis of variance confirmed the reaction rate constants for the yellow solutions and emphasized the significance of pH in this process. [ABSTRACT FROM AUTHOR]

Accessory liver lobe is a rare finding, with the most common cases being accessory liver tissue on the gallbladder wall separate from the orthotopic liver. As the incidence of the ectopic liver is low there are only several case reports in published literature that describe similar presentations. We report a case of intrathoracic liver lobe that was connected to the main liver by a thick pedicle. Due to benign presentation, the patient was discharged without any surgical intervention. This case highlights the importance of understanding anatomical variability of internal organs, understanding the risks of torsion and malignant transformation of the accessory liver tissue. The literature review provides an excellent overview of published case series and reports, and outlines current recommendations on imaging, diagnosis, and management. [ABSTRACT FROM AUTHOR]

Relativistic dissipative fluid dynamics finds widespread applications in high-energy nuclear physics and astrophysics. However, formulating a causal and stable theory of relativistic dissipative fluid dynamics is far from trivial; efforts to accomplish this reach back more than 50 years. In this review, we give an overview of the field and attempt a comparative assessment of (at least most of) the theories for relativistic dissipative fluid dynamics proposed until today and used in applications. [ABSTRACT FROM AUTHOR]

Fruitlet calyx shedding in pear plants is apparently regulated via numerous pathways that involve both environmental triggers and phytohormones cues such as auxin. In this study, we found at 10 days after full bloom (DAFB) higher levels of indoleacetic acid (IAA) and tryptophan (Trp) in calyx persistence fruitlet (CPF) than calyx shedding fruitlet (CSF) of 'Danshan Suli' pear (Pyrus bretschneideri Rhed.). Consisting with this, the activity of indolealdehyde oxidase (IAAIdO), which promotes IAA synthesis, was remarkably increased, and that of peroxidase (POD), which degrades IAA, dropped markedly in CPF but not in CSF. Further, qRT-PCR results revealed that most of 31 PbrARFs (encoding auxin response factors) in Pyrus bretschneideri were highly expressed in CPF, whereas PbrARF4, PbrARF24 and PbrARF26 were significantly downregulated in CPF vis-a-vis CSF. Phylogenetic analysis revealed that 6 PbrARFs clustered in the group III, where PbrARF4 showed the closest affinity with AtARF1 that promotes organ abscission, indicating a putative role of PbrARF4 in mediating the process of calyx shedding in pear. In fact, the ectopic overexpression of PbrARF4 in Solanum lycopersicum resulted in an earlier-formed and deeper abscission layer (AL) in the transgenic plants, whose calyxes were more prone to wilt at the mature red stage (MR) compared with the control plants (wild-type). More importantly, expression levels of the abscission genes SlLS and SlCel2 in transgenic plants overexpressing PbrARF4 were significantly upregulated in comparation with the WT, whereas those of SlBI and SlTAPG2 were considerably inhibited. Further, PbrJOINTLESS and PbrIDA, the two genes related to calyx shedding in pear, were up-regulated more in CSF than CPF. The findings contribute to a better understanding of PbrARFs involved in fruitlet calyx shedding of pear, which could prove beneficial to improving the quality of pear fruit. [ABSTRACT FROM AUTHOR]

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Background: The use of phytosterols and phytostanols (PS) as food supplements to control plasma cholesterol concentrations has recently received attention as its efficacy has been endorsed by scientific authorities and leading guidelines. However, the effects of phytosterols on lipid profiles and atherosclerosis remain incomplete and controversial. This study aims to investigate the effects of PS supplementation on lipid profiles and apolipoproteins in adults based on a systematic review of the literature and a meta-analysis of randomized controlled trials (RCTs)., Methods: A comprehensive search was conducted for RCTs published in PubMed, Embase, Cochrane Library, and Web of Science as of May 2024. Random effects model was utilized to determine the mean differences and 95% confidence interval for changes in circulating lipid profiles and apolipoproteins., Results: Twenty-eight RCTs with a total of 1777 participants (895 cases and 882 controls) are included in the qualitative synthesis. PS supplementation significantly reduced total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and apolipoprotein B (Apo-B) levels, as well as Apo-B/apolipoprotein A1 ratios, but increased high-density lipoprotein cholesterol levels. PS supplementation dose is associated with TC, LDL-c, and Apo-B levels in a dose-response manner., Conclusion: Our findings suggest that dietary phytosterols can effectively promote the reduction of TC, LDL-c, and Apo-B, along with increased high-density lipoprotein cholesterol in adults., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome characterized by the coexistence of emphysema and fibrotic interstitial lung disease (ILD). The aim of this study was to examine the effect of CPFE on lung cancer risk and lung cancer-related mortality in patients with rheumatoid arthritis (RA). Methods: We conducted a multicenter retrospective cohort study of patients newly diagnosed with lung cancer at five community hospitals between June 2006 and December 2021. Patients were followed until lung cancer-related death, other-cause death, loss to follow-up, or the end of the study. We used the cumulative incidence function with Gray's test and Fine-Gray regression analysis for survival analysis. Results: A total of 563 patients with biopsy-proven lung cancer were included (82 RA patients and 481 non-RA patients). The prevalence of CPFE was higher in RA patients than in non-RA patients (40.2% vs.10.0%) at lung cancer diagnosis. During follow-up, the crude incidence rate of lung cancer-related death was 0.29 and 0.10 per patient-year (PY) in RA and non-RA patients, and 0.32 and 0.07 per PY in patients with CPFE and patients without ILD or emphysema, respectively. The estimated death probability at 5 years differed between RA and non-RA patients (66% vs. 32%, p<0.001) and between patients with CPFE and patients without ILD or emphysema (71% vs. 24%, p<0.001). In addition to clinical cancer stage and no surgery within 1 month, RA and CPFE were identified as independent predictive factors for increased lung cancer-related mortality (RA: adjusted hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.65–4.76; CPFE: adjusted HR 2.01; 95% CI 1.24–3.23). Conclusions: RA patients with lung cancer had a higher prevalence of CPFE and increased cancer-related mortality compared with non-RA patients. Close monitoring and optimal treatment strategies tailored to RA patients with CPFE are important to improve the poor prognosis of lung cancer. [ABSTRACT FROM AUTHOR]

Atrial fibrillation, a prevalent type of arrhythmia, is increasingly contributing to the economic burden on healthcare systems. The development of innovative treatments, notably catheter ablation, has demonstrated both impressive and promising outcomes. However, these treatments have not yet fully replaced pharmaceutical approaches, primarily due to the relatively high incidence of atrial fibrillation recurrence post-procedure. Recent insights into endothelial dysfunction have shed light on its role in both the onset and progression of atrial fibrillation. This emerging understanding suggests that endothelial function might significantly influence the effectiveness of catheter ablation. Consequently, a deeper exploration into endothelial dynamics could potentially elevate the status of catheter ablation, positioning it as a primary treatment option for atrial fibrillation. [ABSTRACT FROM AUTHOR]

The interplay between metal ion binding and the activity of thiol proteins, particularly within the protein disulfide isomerase family, remains an area of active investigation due to the critical role that these proteins play in many vital processes. This research investigates the interaction between recombinant human PDIA1 and zinc ions, focusing on the subsequent implications for PDIA1's conformational stability and enzymatic activity. Employing isothermal titration calorimetry and differential scanning calorimetry, we systematically compared the zinc binding capabilities of both oxidized and reduced forms of PDIA1 and assessed the structural consequences of this interaction. Our results demonstrate that PDIA1 can bind zinc both in reduced and oxidized states, but with significantly different stoichiometry and more pronounced conformational effects in the reduced form of PDIA1. Furthermore, zinc binding was observed to inhibit the catalytic activity of reduced-PDIA1, likely due to induced alterations in its conformation. These findings unveil a potential regulatory mechanism in PDIA1, wherein metal ion binding under reductive conditions modulates its activity. Our study highlights the potential role of zinc in regulating the catalytic function of PDIA1 through conformational modulation, suggesting a nuanced interplay between metal binding and protein stability in the broader context of cellular redox regulation. [ABSTRACT FROM AUTHOR]

Hemophilia is a congenital disorder associated with impaired blood clotting. Routine dental intervention to prevent oral bleeding in patients with hemophilia is considered important, but its effectiveness remains unknown. In the present study, we evaluated the effect of continual dental support on periodontal status and oral health habits in young patients with hemophilia. Of the 168 young patients with hemophilia who visited our clinic for 5 years, we selected subjects who had visited annually since 2015 and were in the mixed and permanent dentitions. To evaluate the periodontal status of these subjects, Community Periodontal Index (CPI) values in the molars and anterior teeth were measured. In addition, a questionnaire regarding oral health habits, including floss use, frequency of brushing by parents, and attending a family dentist, was administered to the subjects and their parents. In the patients with mixed dentition, the CPI values for the upper right molars and lower left central incisor decreased significantly in later years compared with the first year (p < 0.05). In the patients with permanent dentition, only one year recorded a significant decrease in CPI values compared with the first year (p < 0.05), localized in the upper right molars. The results of the questionnaire revealed that continual dental support improved dental floss use and the frequency of brushing by parents only in the mixed dentition group. Furthermore, these oral health habits significantly affected CPI values only in the mixed dentition group (p < 0.01). These results suggest that continual dental support improves the periodontal condition and oral health habits of hemophilic patients, especially those with mixed dentition. [ABSTRACT FROM AUTHOR]

Coral reefs have been declining worldwide due to multiple threats. Various approaches for coral restoration have been employed to increase coral populations. Sexual propagation is a crucial technique that can enhance the genetic diversity of coral offspring, thereby increasing coral reef resilience in the face of a changing environment. However, the effectiveness of using sexually reared corals for transplantation depends on many factors, including the biological traits of the coral and the physical environment. This study investigated the relationship between Acropora humilis and Symbiodiniaceae during the ontogenetic stages of the coral in ex-situ conditions and after transplantation to a natural reef. Coral sexual propagation techniques were conducted to produce experimental coral colonies. The fertilization rates of coral gametes averaged 98.48 ± 0.34%. However, the survival rate of juvenile corals gradually declined to 45.96 ± 1.31% at 18 months old under hatchery conditions and to 20% after transplantation to a natural reef. Acropora humilis associated with Symbiodiniaceae lineages belonging to three genera: Symbiodinium, Cladocopium, and Durusdinium. Reared juvenile corals developed a more specific and stable association with particular Symbiodiniaceae under hatchery conditions, whereas after transplantation, corals tended to contain a higher diversity of Symbiodiniaceae lineages. These results indicate that a shift in Symbiodiniaceae composition can provide longterm benefits to corals during their ontogenetic cycle and when the environment changes. [ABSTRACT FROM AUTHOR]

Pulmonary artery catheterization (PAC) has been used as a clinical standard for cardiac output (CO) measurements on humans. On animals, however, an ultrasonic flow sensor (UFS) placed around the ascending aorta or pulmonary artery can measure CO and stroke volume (SV) more accurately. The objective of this paper is to compare CO and SV measurements using a noninvasive electrical impedance tomography (EIT) device and three invasive devices using UFS, PAC-CCO (continuous CO) and arterial pressure-based CO (APCO). Thirty-two pigs were anesthetized and mechanically ventilated. A UFS was placed around the pulmonary artery through thoracotomy in 11 of them, while the EIT, PAC-CCO and APCO devices were used on all of them. Afterload and contractility were changed pharmacologically, while preload was changed through bleeding and injection of fluid or blood. Twenty-three pigs completed the experiment. Among 23, the UFS was used on 7 pigs around the pulmonary artery. The percentage error (PE) between COUFS and COEIT was 26.1%, and the 10-min concordance was 92.5%. Between SVUFS and SVEIT, the PE was 24.8%, and the 10-min concordance was 94.2%. On analyzing the data from all 23 pigs, the PE between time-delay-adjusted COPAC-CCO and COEIT was 34.6%, and the 10-min concordance was 81.1%. Our results suggest that the performance of the EIT device in measuring dynamic changes of CO and SV on mechanically-ventilated pigs under different cardiac preload, afterload and contractility conditions is at least comparable to that of the PAC-CCO device. Clinical studies are needed to evaluate the utility of the EIT device as a noninvasive hemodynamic monitoring tool. [ABSTRACT FROM AUTHOR]

Fascioliasis is a neglected tropical zoonotic disease caused by liver flukes belonging to the genus Fasciola. The emergence of resistance to triclabendazole, the only World Health Organization-recommended drug for this disease, highlights the need for the development of new drugs. Helminths possess an anaerobic mitochondrial respiratory chain (fumarate respiration) which is considered a potential drug target. This study aimed to evaluate the occurrence of fumarate respiration in Fasciola flukes. We analyzed the properties of the respiratory chain of Fasciola flukes in both adults and newly excysted juveniles (NEJs). Fasciola flukes travel and mature through the stomach, bowel, and abdominal cavity to the liver, where oxygen levels gradually decline. High fumarate reductase activity was observed in the mitochondrial fraction of adult Fasciola flukes. Furthermore, rhodoquinone-10 (RQ10 Em’= −63 mV), a low-potential electron mediator used in fumarate respiration was found to be predominant in adults. In contrast, the activity of oxygen respiration was low in adults. Rotenone, atpenin A5, and ascochlorin, typical inhibitors of mitochondrial enzymes in complexes I, II, and III, respectively, inhibit the activity of each enzyme in the adult mitochondrial fraction. These inhibitors were then used for in vitro viability tests of NEJs. Under aerobic conditions, NEJs were killed by rotenone or ascochlorin, which inhibit aerobic respiration (complex I–III), whereas atpenin A5, which inhibits complex II involved in fumarate respiration, did not affect NEJs. Moreover, ubiquinone-10 (UQ10 Em’= +110 mV), which is used in oxidative respiration, was detected in NEJs, in addition to RQ10. In contrast, under anaerobic conditions, rotenone and atpenin A5, which inhibit fumarate respiration (complex I–II), were crucial for NEJs. These findings demonstrate that NEJs have active hybrid respiration, in which they can properly use both oxygen and fumarate respiration, depending on oxygen availability. Thus, fumarate respiration is a promising drug target for Fasciola flukes, because it plays an essential role in both adults and NEJs. [ABSTRACT FROM AUTHOR]

Contractile rings are formed from cytoskeletal filaments during cell division. Ring formation is induced by specific crosslinkers, while contraction is typically associated with motor protein activity. Here, we engineer DNA nanotubes and peptide-functionalized starPEG constructs as synthetic crosslinkers to mimic this process. The crosslinker induces bundling of ten to hundred DNA nanotubes into closed micron-scale rings in a one-pot self-assembly process yielding several thousand rings per microliter. Molecular dynamics simulations reproduce the detailed architectural properties of the DNA rings observed in electron microscopy. Theory and simulations predict DNA ring contraction – without motor proteins – providing mechanistic insights into the parameter space relevant for efficient nanotube sliding. In agreement between simulation and experiment, we obtain ring contraction to less than half of the initial ring diameter. DNA-based contractile rings hold promise for an artificial division machinery or contractile muscle-like materials.Contractile rings are formed from cytoskeletal filaments, specific crosslinkers and motor proteins during cell division. Here, authors form micron-scale contractile DNA rings from DNA nanotubes and synthetic crosslinkers, with both simulations and experiments showing ring contraction without motor proteins, offering a potential first step towards synthetic cell division machinery. [ABSTRACT FROM AUTHOR]

Methanolic-aqueous extracts of Salvia tomentosa Miller roots, aerial parts, and inflorescences were examined for their content of polyphenolic derivatives and the antimicrobial and cytotoxic effect. In the polyphenolic-rich profile, rosmarinic, salvianolic, and lithospermic acids along with various derivatives were predominant. A total of twenty phenolic compounds were identified using the UPLC/DAD/qTOF-MS technique. These were caffeic acid, rosmarinic acid derivatives, lithospermic acid derivatives, salvianolic acids B, F, and K derivatives, as well as sagerinic acid, although rosmarinic acid (426–525 mg/100 g of dry weight—D.W.) and salvianolic acid B (83–346.5 mg/100 g D.W.) were significantly predominant in the metabolic profile. Strong antibacterial activity of S. tomentosa extracts was observed against Staphylococcus epidermidis (MIC/MBC = 0.625 mg/mL) and Bacillus cereus (MIC = 0.312–1.25 mg/mL). The extracts showed low cytotoxicity towards the reference murine fibroblasts L929 and strong cytotoxicity to human AGS gastric adenocarcinoma epithelial cells in the MTT reduction assay. The observed cytotoxic effect in cancer cells was strongest for the roots of 2-year-old plant extracts. [ABSTRACT FROM AUTHOR]

This paper proposes an alternative mechanism to solve the so-called missing pulsar problem, a standing paradox between the theoretical expectations about the number of pulsars that should exist in the galaxy center of the Milky Way and their absence in the observations. The mechanism is based on the transformation of incident γ rays into hybridized modes, known as axion-polaritons, which can exist inside highly magnetized quark stars with a quark matter phase known as the magnetic dual chiral density wave phase. This phase, which is favored over several other dense matter phases candidates at densities a few times nuclear saturation density, has already passed several important astrophysical tests. In the proposed mechanism, the absence of young magnetars occurs because as electromagnetic waves inside the star can only propagate through the hybridized modes, incident photons coming from a γ -ray burst get transformed into massless and massive axion polaritons by the Primakoff effect. Once thermalized, the massive axion-polaritons can self-gravitate up to a situation where their total mass overpasses the Chandrasekhar limit for these bosons, producing a mini blackhole that collapses the star. [ABSTRACT FROM AUTHOR]

In this paper, we report on a study regarding the efficiency of the post-operational phototherapy of the tumor bed after resection with both a cold knife and a laser scalpel in laboratory mice with CT-26 tumors. Post-operational processing included photodynamic therapy (PDT) with a topically applied chlorin-based photosensitizer (PS), performed at wavelengths of 405 or 660 nm, with a total dose of 150 J/cm2. The selected design of the tumor model yielded zero recurrence in the laser scalpel group and 92% recurrence in the cold knife group without post-processing, confirming the efficiency of the laser scalpel in oncology against the cold knife. The application of PDT after the cold knife resection decreased the recurrence rate to 70% and 42% for the 405 nm and 660 nm procedures, respectively. On the other hand, the application of PDT after the laser scalpel resection induced recurrence rates of 18% and 30%, respectively, for the considered PDT performance wavelengths. The control of the penetration of PS into the tumor bed by fluorescence confocal microscopy indicated the deeper penetration of PS in the case of the cold knife, which presumably provided deeper PDT action, while the low-dose light exposure of deeper tissues without PS, presumably, stimulated tumor recurrence, which was also confirmed by the differences in the recurrence rate in the 405 and 660 nm groups. Irradiation-only light exposures, in all cases, demonstrated higher recurrence rates compared to the corresponding PDT cases. Thus, the PDT processing of the tumor bed after resection could only be recommended for the cold knife treatment and not for the laser scalpel resection, where it could induce tumor recurrence. [ABSTRACT FROM AUTHOR]

The strength of the lateral flexor muscles in the trunk is necessary for maintaining stability in the rib cage, spinal column, and preventing a higher number of injuries, while also enhancing overall trunk muscle strength. This study, conducted in a transversal manner, aimed to identify gender-based differences in the strength of trunk lateral flexor muscles among university athletes in the younger senior age group. The study involved 46 athletes from the University of Novi Sad, comprising 25 male participants (height =181.27±6.28 cm; weight =78.31±12.14 kg; BMI =23.78±3.13 kg/m2; mean age =23.75±0.30) and 21 female participants (height =168.19±5.48 cm; weight = 3.72±5.94 kg; BMI =22.53±7.78 kg/m2; mean age =23.68±0.22). The results of the independent t-test revealed no statistically significant differences between the two gender groups based on dimorphic characteristics (p>0.05) in the assessment of trunk lateral flexor muscle strength. It is essential to consider other aspects of the locomotor system specific to each sport and discipline to effectively prevent injuries during training and decrease the overall injury rate. [ABSTRACT FROM AUTHOR]

Background and Objectives: Our research group developed a robot-assisted diabetes self-management monitoring system to support Certified Diabetes Care and Education Specialists (CDCESs) in tracking the health status of patients with type 2 diabetes (T2D). This study aimed to evaluate the impact of this system on glycemic control and to identify suitable candidates for its use. Materials and Methods: After obtaining written informed consent from all participants with T2D, the CDCESs conducted remote interviews with the patients using RoBoHoN. All participants completed a questionnaire immediately after the experiment. HbA1c was assessed at the time of the interview and two months later, and glycemic control status was categorized as either "Adequate" or "Inadequate" based on the target HbA1c levels outlined in the guidelines for adult and elderly patients with type 2 diabetes by the Japan Diabetes Society. Patients who changed their medication regimens within the two months following the interview were excluded from the study. Results: The clinical characteristics of the 28 eligible patients were as follows: 67.9 ± 14.8 years old, 23 men (69%), body mass index (24.7 ± 4.9 kg/m2), and HbA1c levels 7.16 ± 1.11% at interview and two months later. Glycemic control status (GCS) was Adequate (A) to Inadequate (I): 1 case; I to A: 7 cases; A to A good: 14 cases; I to I: 6 cases (p-value = 0.02862 by Chi-square test). Multiple regression analyses showed that Q1 (Did RoBoHoN speak clearly?) and Q7 (Was RoBoHoN's response natural?) significantly contributed to GCS, indicating that the naturalness of the responses did not impair the robot-assisted interviews. The results suggest that to improve the system in the future, it is more beneficial to focus on the content of the conversation rather than pursuing superficial naturalness in the responses. Conclusions: This study demonstrated the efficacy of a robot-assisted diabetes management system that can contribute to improved glycemic control. [ABSTRACT FROM AUTHOR]

Knowledge of coral larval precompetency periods and maximum competency windows is fundamental to understanding coral population dynamics, informing biogeography and connectivity patterns, and predicting reef recovery following disturbances. Yet for many species, estimates of these early-life history metrics are scarce and vary widely. Furthermore, settlement cues for many taxa are not known despite consequences to habitat selection. Here we performed a comprehensive experimental time-series investigation of larval settlement behaviour, for 25 Indo-Pacific broadcast-spawning species. To investigate the duration of precompetency, improve predictions of the competency windows, and compare settlement responses within and amongst species, we completed replicated and repeated 24-hour assays that exposed larvae to five common settlement cues. Our study revealed that larval competency in some broadcast-spawning species begins as early as two days post fertilization, but that the precompetency period varies within and between species from about two to six days, with consequences for local retention and population connectivity. We also found that larvae of some species are competent to settle beyond 70 days old and display complex temporal settlement behaviour, challenging the assumption that competency gradually wanes over time and adding to the evidence that larval longevity can support genetic connectivity and long-distance dispersal. Using these data, we grouped coral taxa by short, mid and long precompetency periods, and identified their preferred settlement cues. Taken together, these results inform our understanding of larval dynamics across a broad range of coral species and can be applied to investigations of population dynamics, connectivity, and reef recovery. An assay-based laboratory study that defines precompetency durations of 2 – 6 days and compares settlement preference amongst common inducers, for 25 Scleractinian Indo-Pacific coral species. [ABSTRACT FROM AUTHOR]

Introduction: The excretion and absorption of uric acid (UA) by the kidneys helps regulate serum UA levels. GLUT9, encoded by SLC2A9, is mainly expressed in the renal tubules responsible for UA absorption. SLC2A9 polymorphisms are associated with different serum UA levels. However, the lack of proper in vitro models has stalled research on the mechanisms of single nucleotide polymorphisms (SNPs) that affect UA metabolism in human urate transporters. Methods: In this study, we constructed a gene-edited human embryonic stem cells-9 (ESC-H9) derived kidney organoid bearing rs16890979, an SLC2A9 missense mutation with undetermined associations with hyperuricemia or hypouricemia. Kidney organoids derived from ESC-H9 with genetical overexpression (OE) and low expression (shRNA) of SLC2A9 to serve as controls to study the function of SLC2A9. The function of rs16890979 on UA metabolism was evaluated after placing the organoids to urate-containing medium and following histopathological analysis. Results: The kidney organoids with heterozygous or homozygous rs16890979 mutations showed normal SLC2A9 expression levels and histological distribution, phenotypically similar to the wild-type controls. However, reduced absorption of UA by the kidney organoids with rs16890979 mutants was observed. This finding together with the observation that UA absorption is increased in organoids with SLC2A9 overexpression and decreased in those with SLC2A9 knockdown, suggest that GLUT9 is responsible for UA absorption, and the rs16890979 SNP may compromise this functionality. Moreover, epithelial-mesenchymal transition (EMT) was detected in organoids after UA treatment, especially in the kidney organoid carrying GLUT9OE, suggesting the cytobiological mechanism explaining the pathological features in hyperuricosuria-related renal injury. Discussion: This study showing the transitional value of kidney organoid modeling the function of SNPs on UA metabolism. With a defined genetic background and a confirmed UA absorption function should be useful for studies on renal histological, cellular, and molecular mechanisms with this organoid model. [ABSTRACT FROM AUTHOR]

Simple Summary: Research on the clinical impact of body composition parameters, such as myosteatosis, in patients with hepatocellular carcinoma (HCC) is limited. Our study examined the effects of computed tomography-based body composition measurements and traditional risk factors on the survival outcomes of sorafenib-treated HCC patients. Myosteatosis, evaluated using Hounsfield units, is associated with unfavorable survival outcomes, independent of traditional risk factors including vascular invasion, extrahepatic metastasis, and high alpha-fetoprotein levels. Two or more of these risk factors are associated with adverse outcomes. Thus, myosteatosis could serve as a prognostic factor in sorafenib-treated HCC patients. The role of body composition parameters in sorafenib-treated hepatocellular carcinoma (HCC) patients is still not fully elucidated. Here, we aimed to evaluate the impact of computed tomography (CT)-based body composition parameters on the survival of such patients. In this multicenter study, we analyzed the data of 245 sorafenib-treated HCC patients from January 2008 to December 2019. Sarcopenia, visceral obesity, and myosteatosis were defined by using cross-sectional CT images at the third lumbar vertebra level. The effects of these parameters on overall survival (OS) and progression-free survival (PFS) were evaluated. The median age was 67.0 years (interquartile range: 61.0–78.0 year), and 211 patients (86.1%) were male. The median OS and PFS were 7.9 months and 4.8 months, respectively. Vascular invasion (hazard ratio (HR), 1.727; 95% confidence interval (CI), 1.258–2.371; p = 0.001), extrahepatic metastasis (HR, 1.401; 95% CI, 1.028–1.908; p = 0.033), alpha-fetoprotein level > 200 ng/mL (HR, 1.559; 95% CI, 1.105–2.201; p = 0.012), and myosteatosis (HR, 1.814; 95% CI, 1.112–2.960; p = 0.017) were associated with OS. Patient mortality was significantly higher in the group with two or more risk factors than in the group with fewer risk factors. In conclusion, myosteatosis may be a novel prognostic CT-based radiological biomarker in sorafenib-treated HCC patients. [ABSTRACT FROM AUTHOR]

The importance of salt intake in preventing heat-related illness (HRI) is well established, however, the specific method of ingestion has not been sufficiently studied. This study, therefore, aimed to investigate the optimal timing of salt intake to prevent HRI during hot outdoor work. We recruited 28 healthy male firefighters working at a fire department in Japan. They were provided a questionnaire to complete before and after receiving training in the summer season. We assessed their salt intake as before, during, and after training or none. In addition, they completed a brief self-administered diet history questionnaire to evaluate their daily salt and alcohol intake. HRI was determined through subjective and objective symptoms listed in the questionnaire, and environmental data were obtained from a national database. Subsequently, factors related to HRI were determined using a logistic regression model. The mean age of the participants was 31.0 ± 7.7 years. The study was performed within 250 working days, and we detected 28 HRI symptoms (11.2%). The median alcohol intake was 25.6 g/day when calculated according to the actual work system. Logistic mixed effect model analysis revealed that salt intake before training (OR: 5.893, 95% CI: 1.407–24.675), and salt intake before and during training (OR: 22.889, 95% CI: 4.276–122.516) were positively associated with HRI symptoms. The results indicate that inappropriate timing of salt intake increases the risks of HRI. Thus, a timely intake of salt in adequate amounts may be important in preventing these risks. [ABSTRACT FROM AUTHOR]

Background: Corticocancellous bone grafting from the iliac crest is acceptable treatment for unstable scaphoid nonunion with a viable proximal pole. However, harvesting graft from the iliac crest is associated with donor site morbidity and the requirement of general anesthesia. Thus, bone grafting from the anterolateral metaphysis of the distal radius (DR) can be a treatment option. However, no study has compared the clinical effect between the two grafting techniques. Methods: From 2014 to 2019, patients with unstable scaphoid nonunion with humpback deformity underwent corticocancellous bone grafting from the anterolateral metaphysis of the DR (group DR) or iliac crest (group IC). Humpback deformity was determined by evaluating the scapholunate angle (SLA) ≥ 60°, intrascaphoid angle (ISA) ≥ 45°, and radiolunate angle (RLA) ≥ 15° from preoperative radiographs and computed tomography scans. The SLA, ISA, and RLA served to gauge carpal alignment. The operative time, grip strength, active range of motion (ROM), the Modified Mayo Wrist score (MMWS), and Disabilities of Arm, Shoulder, and Hand (DASH) score were assessed postoperatively. Results: Thirty-eight patients qualified for the study (group DR, 15; group IC, 23). Union rates did not differ by patient subset (group DR, 100%; group IC, 95.7%; P =.827), and grip strength, ROM, MWS, and DASH score were similar between groups at the last follow-up. The operative time (minutes) was significantly shorter in group DR (median, 98; quartiles, 80, 114) than in group IC (median, 125; quartiles, 105, 150, P <.001). The ISA, RLA, and SLA improved postoperatively in both groups (P < 0.001). The degree of restoring carpal alignment, as evaluated by SLA, showed superior correction capability in group DR (median, 25.3% quartiles, 21.1, 35.3, P < 0.05). Donor site complications were not significantly different between the groups. Conclusions: Corticocancellous bone graft from the anterolateral metaphysis of the DR for unstable scaphoid nonunion is associated with a shorter operation time and comparable results with that from the iliac crest in regard to union, restoration of carpal alignment, and wrist function. Level of Evidence: Level III. [ABSTRACT FROM AUTHOR]

G-quadruplexes, intricate four-stranded structures composed of G-tetrads formed by four guanine bases, are prevalent in both DNA and RNA. Notably, these structures play pivotal roles in human telomeres, contributing to essential cellular functions. Additionally, the existence of DNA:RNA hybrid G-quadruplexes adds a layer of complexity to their structural diversity. This review provides a comprehensive overview of recent advancements in unraveling the intricacies of DNA and RNA G-quadruplexes within human telomeres. Detailed insights into their structural features are presented, encompassing the latest developments in chemical approaches designed to probe these G-quadruplex structures. Furthermore, this review explores the applications of G-quadruplex structures in targeting human telomeres. Finally, the manuscript outlines the imminent challenges in this evolving field, setting the stage for future investigations. [ABSTRACT FROM AUTHOR]

Podocyte injury can disrupt the glomerular filtration barrier (GFB), leading to podocytopathies that emphasize podocytes as the glomerulus's key organizer. The coordinated cytoskeleton is essential for supporting the elegant structure and complete functions of podocytes. Therefore, cytoskeleton rearrangement is closely related to the pathogenesis of podocytopathies. In podocytopathies, the rearrangement of the cytoskeleton refers to significant alterations in a string of slit diaphragm (SD) and focal adhesion proteins such as the signaling node nephrin, calcium influx via transient receptor potential channel 6 (TRPC6), and regulation of the Rho family, eventually leading to the disorganization of the original cytoskeletal architecture. Thus, it is imperative to focus on these proteins and signaling pathways to probe the cytoskeleton rearrangement in podocytopathies. In this review, we describe podocytopathies and the podocyte cytoskeleton, then discuss the molecular mechanisms involved in cytoskeleton rearrangement in podocytopathies and summarize the effects of currently existing drugs on regulating the podocyte cytoskeleton. [ABSTRACT FROM AUTHOR]