BFGF attenuates aortic valvular interstitial cell calcification by inhibiting endoplasmic reticulum stress-mediated apoptosis.

The potential protective effect of basic fibroblast growth factor (BFGF) on the cardiovascular system has been proposed previously, however, its effect on calcific aortic valve disease (CAVD) and underlying mechanisms have not been elucidated. The valvular interstitial cell (VIC) were isolated from porcine aortic valve leaflets. To investigate the effect of BFGF on osteogenic differentiation of VIC, the osteogenic induced medium (OIM) and BFGF were added. The protein expression level was detected by Western blot, and apoptosis was determined by flow cytometry. The effect of BFGF on CAVD process in vivo was assessed by a rat CAVD model, which was identified by echocardiography and Alizarin red staining. The expression level of BFGF in the aortic valve and serum were significantly upregulated in CAVD patients compared to control group. In addition, exogenous BFGF injection attenuates CAVD process in vivo. The protein markers of osteogenic differentiation, endoplasmic reticulum stress (ERS), and apoptosis were significantly upregulated by culture with OIM. On the contrary, the aforementioned proteins were suppressed after adding 100 ng/mL of BFGF. Inhibition of PI3K/Akt and ERK1/2 pathways by specific inhibitors abolished the protective effect of BFGF. In conclusion, BFGF could alleviate the VIC calcification by inhibiting ERS-mediated apoptosis, which is partly regulated by activation of the PI3K/Akt and ERK1/2 signaling pathways. BFGF may provide a potential avenue for CAVD therapy.

Quantifying the hydrodynamic contribution to electrical transport in non-Brownian suspensions.

Electrical transport in semiconducting and metallic particle suspensions is an enabling feature of emerging grid-scale battery technologies. Although the physics of the transport process plays a key role in these technologies, no universal framework has yet emerged. Here, we examine the important contribution of shear flow to the electrical transport of non-Brownian suspensions. We find that these suspensions exhibit a strong dependence of the transport rate on the particle volume fraction and applied shear rate, which enables the conductivity to be dynamically changed by over 107 decades based on the applied shear rate. We combine experiments and simulations to conclude that the transport process relies on a combination of charge and particle diffusion with a rate that can be predicted using a quantitative physical model that incorporates the self-diffusion of the particles.

A distinct dimer configuration of a diatom Get3 forming a tetrameric complex with its tail-anchored membrane cargo.

BACKGROUND: Most tail-anchored (TA) membrane proteins are delivered to the endoplasmic reticulum through a conserved posttranslational pathway. Although core mechanisms underlying the targeting and insertion of TA proteins are well established in eukaryotes, their role in mediating TA protein biogenesis in plants remains unclear. We reported the crystal structures of algal arsenite transporter 1 (ArsA1), which possesses an approximately 80-kDa monomeric architecture and carries chloroplast-localized TA proteins. However, the mechanistic basis of ArsA2, a Get3 (guided entry of TA proteins 3) homolog in plants, for TA recognition remains unknown. RESULTS: Here, for the first time, we present the crystal structures of the diatom Pt-Get3a that forms a distinct ellipsoid-shaped tetramer in the open (nucleotide-bound) state through crystal packing. Pulldown assay results revealed that only tetrameric Pt-Get3a can bind to TA proteins. The lack of the conserved zinc-coordination CXXC motif in Pt-Get3a potentially leads to the spontaneous formation of a distinct parallelogram-shaped dimeric conformation in solution, suggesting a new dimer state for subsequent tetramerization upon TA targeting. Pt-Get3a nonspecifically binds to different subsets of TA substrates due to the lower hydrophobicity of its α-helical subdomain, which is implicated in TA recognition. CONCLUSIONS: Our study provides new insights into the mechanisms underlying TA protein shielding by tetrameric Get3 during targeting to the diatom's cell membrane.

Near Infrared-II Excited Triplet Fusion Upconversion with Anti-Stokes Shift Approaching the Theoretical Limit.

The anti-Stokes shift represents the capacity of photon upconversion to convert low-energy photons to high-energy photons. Although triplet exciton-mediated photon upconversion presents outstanding performance in solar energy harvesting, photoredox catalysis, stereoscopic 3D printing, and disease therapeutics, the interfacial multistep triplet exciton transfer leads to exciton energy loss to suppress the anti-Stokes shift. Here, we report near infrared-II (NIR-II) excitable triplet exciton-mediated photon upconversion using a hybrid photosensitizer consisting of lead sulfide quantum dots (PbS QDs) and new surface ligands of thiophene-substituted diketopyrrolopyrrole (Th-DPP). Under 1064 nm excitation, this photon upconversion revealed a record-corrected upconversion efficiency of 0.37% (normalized to 100%), with the anti-Stokes shift (1.07 eV) approaching the theoretical limit (1.17 eV). The observation of this unexpected result is due to our discovery of the presence of a weak interaction between the sulfur atom on Th-DPP and Pb2+ on the PbS QDs surface, facilitating electronic coupling between PbS QDs and Th-DPP, such that the realization of triplet exciton transfer efficiency is close to 100% even when the energy gap is as small as 0.04 eV. With this premise, this photon upconversion as a photocatalyst enables the production of standing organic gel via photopolymerization under 1064 nm illumination, displaying NIR-II photon-driven photoredox catalysis. This research not only establishes the foundation for enhancing the performance of NIR-II excitable photonic upconversion but also promotes its development in photonics and photoredox catalysis.

EIF4A3-negatively driven circular RNA ß-catenin (circß-catenin) promotes colorectal cancer progression via miR-197-3p/CTNND1 regulatory axis.

BACKGROUND: Circß-catenin, our first reported circRNA, has been reported to mediate tumorigenesis in various cancers. However, its biological functions and underlying mechanisms in colorectal cancer (CRC) remain unknown. METHODS: The qRT-PCR examination was used to detect the expression of circß-catenin, miR-197-3p, and CTNND1 in cells and human tissues. Western blot was conducted to detect the protein expression levels. The biological function of circß-catenin was verified by MTT, colony formation, wound healing, and transwell assays. The in vivo effects of circß-catenin were verified by nude mice xenograft and metastasis models. The regulatory network of circß-catenin/miR-197-3p/CTNND1 was confirmed via dual-luciferase reporter and RIP assays. RESULTS: In the present study, circß-catenin was found to promote CRC cell proliferation and metastasis in vitro and in vivo. Mechanistically, circß-catenin served as miRNA decoy to directly bind to miR-197-3p, then antagonized the repression of the target gene CTNND1, and eventually promoted the malignant phenotype of CRC. More interestingly, the inverted repeated Alu pairs termed AluJb1/2 and AluY facilitated the biogenesis of circß-catenin, which could be partially reversed by EIF4A3 binding to Alu element AluJb2. CONCLUSIONS: Our findings illustrated a novel mechanism of circß-catenin in modulating CRC tumorigenesis and metastasis, which provides a potential therapeutic target for CRC patients.

Critical roles of tubular mitochondrial ATP synthase dysfunction in maleic acid-induced acute kidney injury.

Maleic acid (MA) induces renal tubular cell dysfunction directed to acute kidney injury (AKI). AKI is an increasing global health burden due to its association with mortality and morbidity. However, targeted therapy for AKI is lacking. Previously, we determined mitochondrial-associated proteins are MA-induced AKI affinity proteins. We hypothesized that mitochondrial dysfunction in tubular epithelial cells plays a critical role in AKI. In vivo and in vitro systems have been used to test this hypothesis. For the in vivo model, C57BL/6 mice were intraperitoneally injected with 400 mg/kg body weight MA. For the in vitro model, HK-2 human proximal tubular epithelial cells were treated with 2 mM or 5 mM MA for 24 h. AKI can be induced by administration of MA. In the mice injected with MA, the levels of blood urea nitrogen (BUN) and creatinine in the sera were significantly increased (p < 0.005). From the pathological analysis, MA-induced AKI aggravated renal tubular injuries, increased kidney injury molecule-1 (KIM-1) expression and caused renal tubular cell apoptosis. At the cellular level, mitochondrial dysfunction was found with increasing mitochondrial reactive oxygen species (ROS) (p < 0.001), uncoupled mitochondrial respiration with decreasing electron transfer system activity (p < 0.001), and decreasing ATP production (p < 0.05). Under transmission electron microscope (TEM) examination, the cristae formation of mitochondria was defective in MA-induced AKI. To unveil the potential target in mitochondria, gene expression analysis revealed a significantly lower level of ATPase6 (p < 0.001). Renal mitochondrial protein levels of ATP subunits 5A1 and 5C1 (p < 0.05) were significantly decreased, as confirmed by protein analysis. Our study demonstrated that dysfunction of mitochondria resulting from altered expression of ATP synthase in renal tubular cells is associated with MA-induced AKI. This finding provides a potential novel target to develop new strategies for better prevention and treatment of MA-induced AKI.

Inhibition of visceral adipose tissue-derived pathogenic signals by activation of adenosine A2AR improves hepatic and cardiac dysfunction of NASH mice.

A2AR-disrupted mice is characterized by severe systemic and visceral adipose tissue (VAT) inflammation. Increasing adenosine cyclase (AC), cAMP, and protein kinase A (PKA) formation through A2AR activation suppress systemic/VAT inflammation in obese mice. This study explores the effects of 4 wk A2AR agonist PSB0777 treatment on the VAT-driven pathogenic signals in hepatic and cardiac dysfunction of nonalcoholic steatohepatitis (NASH) obese mice. Among NASH mice with cardiac dysfunction, simultaneous decrease in the A2AR, AC, cAMP, and PKA levels were observed in VAT, liver, and heart. PSB0777 treatment significantly restores AC, cAMP, PKA, and hormone-sensitive lipase (HSL) levels, decreased SREBP-1/FASN, MCP-1, and CD68 levels, reduces infiltrated CD11b+ F4/80+ cells and adipogenesis in VAT of NASH + PSB0777 mice. The changes in VAT were accompanied by the suppression of hepatic and cardiac lipogenic/inflammatory/injury/apoptotic/fibrotic markers, the normalization of cardiac contractile [sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2)] marker, and cardiac dysfunction. The in vitro approach revealed that conditioned media (CM) of VAT of NASH mice (CMnash) trigger palmitic acid (PA)-like lipotoxic (lipogenic/inflammatory/apoptotic/fibrotic) effects in AML-12 and H9c2 cell systems. Significantly, A2AR agonist pretreatment-related normalization of A2AR-AC-cAMP-PKA levels was associated with the attenuation of CMnash-related upregulation of lipotoxic markers and the normalization of lipolytic (AML-12 cells) or contractile (H9C2 cells) marker/contraction. The in vivo and in vitro experiments revealed that A2AR agonists are potential agent to inhibit the effects of VAT inflammation-driven pathogenic signals on the hepatic and cardiac lipogenesis, inflammation, injury, apoptosis, fibrosis, hypocontractility, and subsequently improve hepatic and cardiac dysfunction in NASH mice.NEW & NOTEWORTHY Protective role of adenosine A2AR receptor (A2AR) and AC-cAMP-PKA signaling against nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) possibly via its actions on adipocytes is well known in the past decade. Thus, this study evaluates pharmacological activities of A2AR agonist PSB0777, which has already demonstrated to treat NASH. In this study, the inhibition of visceral adipose tissue-derived pathogenic signals by activation of adenosine A2AR with A2AR agonist PSB0777 improves the hepatic and cardiac dysfunction of high-fat diet (HFD)-induced NASH mice.

Leaping Supercapacitor Performance via a Flash-Enabled Graphene Photothermal Coating.

Elevating the working temperature delivers a simple and universal approach to enhance the energy storage performances of supercapacitors owing to the fundamental improvements in ion transportation kinetics. Among all heating methods, introducing green and sustainable photothermal heating on supercapacitors (SCs) is highly desired yet remains an open challenge, especially for developing an efficient and universal photothermal heating strategy that can be generally applied to arbitrary SC devices. Flash-enabled graphene (FG) absorbers are produced through a simple and facile flash reduction process, which can be coated on the surface of any SC devices to lift their working temperature via a photothermal effect, thus, improving their overall performance, including both power and energy densities. With the systematic temperature-dependent investigation and the in-depth numerical simulation of SC performances, an evident enhancement in capacitance up to 65% can be achieved in photothermally enhanced SC coin cell devices with FG photo-absorbers. This simple, practical, and universal enhancement strategy provides a novel insight into boosting SC performances without bringing complexity in electrode fabrication/optimization. Also, it sheds light on the highly efficient utilization of green and renewable photothermal energies for broad application scenarios, especially for energy storage devices.

Ultrafast Unidirectional On-Chip Heat Transfer.

Effective and rapid heat transfer is critical to improving electronic components' performance and operational stability, particularly for highly integrated and miniaturized devices in complex scenarios. However, current thermal manipulation approaches, including the recent advancement in thermal metamaterials, cannot realize fast and unidirectional heat flow control. In addition, any defects in thermal conductive materials cause a significant decrease in thermal conductivity, severely degrading heat transfer performance. Here, the utilization of silicon-based valley photonic crystals (VPCs) is proposed and numerically demonstrated to facilitate ultrafast, unidirectional heat transfer through thermal radiation on a microscale. Utilizing the infrared wavelength region, the approach achieves a significant thermal rectification effect, ensuring continuous heat flow along designed paths with high transmission efficiency. Remarkably, the process is unaffected by temperature gradients due to the unidirectional property, maintaining transmission directionality. Furthermore, the VPCs' inherent robustness affords defect-immune heat transfer, overcoming the limitations of traditional conduction methods that inevitably cause device heating, performance degradation, and energy waste. The design is fully CMOS compatible, thus will find broad applications, particularly for integrated optoelectronic devices.

Augmenting Neutrophil Extracellular Traps with Carbonized Polymer Dots: A Potential Treatment for Bacterial Sepsis.

Sepsis is a life-threatening condition that can progress to septic shock as the body's extreme response to pathogenesis damages its own vital organs. Staphylococcus aureus (S. aureus) accounts for 50% of nosocomial infections, which are clinically treated with antibiotics. However, methicillin-resistant strains (MRSA) have emerged and can withstand harsh antibiotic treatment. To address this problem, curcumin (CCM) is employed to prepare carbonized polymer dots (CPDs) through mild pyrolysis. Contrary to curcumin, the as-formed CCM-CPDs are highly biocompatible and soluble in aqueous solution. Most importantly, the CCM-CPDs induce the release of neutrophil extracellular traps (NETs) from the neutrophils, which entrap and eliminate microbes. In an MRSA-induced septic mouse model, it is observed that CCM-CPDs efficiently suppress bacterial colonization. Moreover, the intrinsic antioxidative, anti-inflammatory, and anticoagulation activities resulting from the preserved functional groups of the precursor molecule on the CCM-CPDs prevent progression to severe sepsis. As a result, infected mice treated with CCM-CPDs show a significant decrease in mortality even through oral administration. Histological staining indicates negligible organ damage in the MRSA-infected mice treated with CCM-CPDs. It is believed that the in vivo studies presented herein demonstrate that multifunctional therapeutic CPDs hold great potential against life-threatening infectious diseases.

Ultra-compact electro-optic phase modulator based on a lithium niobate topological slow light waveguide.

Electro-optic modulators (EOMs) are essential devices of optical communications and quantum computing systems. In particular, ultra-compact EOMs are necessary for highly integrated photonic chips. Thin film lithium niobate materials are a promising platform for designing highly efficient EOMs. However, EOMs based on conventional waveguide structures are at a millimeter scale and challenging to scale down further, greatly hindering the capability of on-chip integration. Here, we design an EOM based on lithium niobate valley photonic crystal (VPC) structures for the first time. Due to the high effective refractive index introduced by the strong slow light effect, the EOM can achieve an ultra-compact size of 4 µm×14 µm with a half-wave voltage of 1.4 V. The EOM has a high transmittance of 0.87 in the 1068 nm because of the unique spin-valley locking effect in VPC structures. The design is fully compatible with current nanofabrication technology and immune to fabrication defects. Therefore, it opens a new possibility in designing lithium niobate electro-optic modulators and will find broad applications in optical communication and quantum photonic devices.

Mitofilin in cardiovascular diseases: Insights into the pathogenesis and potential pharmacological interventions.

The impact of mitochondrial dysfunction on the pathogenesis of cardiovascular disease is increasing. However, the precise underlying mechanism remains unclear. Mitochondria produce cellular energy through oxidative phosphorylation while regulating calcium homeostasis, cellular respiration, and the production of biosynthetic chemicals. Nevertheless, problems related to cardiac energy metabolism, defective mitochondrial proteins, mitophagy, and structural changes in mitochondrial membranes can cause cardiovascular diseases via mitochondrial dysfunction. Mitofilin is a critical inner mitochondrial membrane protein that maintains cristae structure and facilitates protein transport while linking the inner mitochondrial membrane, outer mitochondrial membrane, and mitochondrial DNA transcription. Researchers believe that mitofilin may be a therapeutic target for treating cardiovascular diseases, particularly cardiac mitochondrial dysfunctions. In this review, we highlight current findings regarding the role of mitofilin in the pathogenesis of cardiovascular diseases and potential therapeutic compounds targeting mitofilin.

Low-Dose Versus Standard-Dose Alteplase in Bridging Therapy for Large Vessel Stroke: A Systematic Review and Meta-Analysis.

INTRODUCTION The efficacy and safety of low- and standard-dose alteplase for acute ischemic stroke (AIS) have not been consistently compared in previous studies. Nevertheless, the distinctions in the effects of low- and standard-dose alteplase, particularly within the context of bridging therapy (BT) for large vessel occlusion (LVO), warrant further exploration. This study compared clinical outcomes between BT with low- and standard-dose alteplase in patients with LVO-related AIS. METHODS We performed a search for randomized controlled trials and prospective or retrospective cohort studies investigating the clinical outcomes of BT in AIS in the PubMed, Embase, and Cochrane Library databases from inception to November 2022. The outcomes of interest were 90-day functional independence, successful recanalization, symptomatic intracerebral hemorrhage (sICH) and mortality; these outcomes were compared between patients who received BT with low- (primarily 0.6 mg/kg) and standard-dose alteplase (0.9 mg/kg). We used the standard-dose group as the reference and calculated the odds ratio (OR) and its 95% confidence interval (CI) from the raw numbers. Meta-analysis and ethnicity-based subgroup analysis (Asian and non-Asian) were performed. RESULTS Five observational studies, published after 2017 and including 408 patients, were included. The meta-analysis results demonstrated that compared with BT with standard-dose alteplase, BT with low-dose alteplase did not improve 90-day functional independence (odds ratio, [OR] 1.02; 95% confidence interval [CI], 0.58-1.80). Nevertheless, BT with low-dose alteplase was associated with a comparable successful recanalization rate (OR, 1.35; 95% CI, 0.68-2.67) and similar sICH incidence (OR 0.36; 95% CI, 0.10-1.36), and mortality (OR, 0.64; 95% CI, 0.27-1.54) compared with BT with standard-dose alteplase; however, the above three results were nonsignificant. In the ethnicity-based subgroup analyses, no differences were noted between Asian and non-Asian participants. CONCLUSIONS In patients with LVO-related AIS, BT with low- or standard-dose alteplase may provide similar efficacy, with no significant differences in sICH incidence and mortality. Additional well-designed prospective studies are required to confirm this result.

Engineering van der Waals Materials for Advanced Metaphotonics.

The outstanding chemical and physical properties of 2D materials, together with their atomically thin nature, make them ideal candidates for metaphotonic device integration and construction, which requires deep subwavelength light-matter interaction to achieve optical functionalities beyond conventional optical phenomena observed in naturally available materials. In addition to their intrinsic properties, the possibility to further manipulate the properties of 2D materials via chemical or physical engineering dramatically enhances their capability, evoking new science on light-matter interaction, leading to leaped performance of existing functional devices and giving birth to new metaphotonic devices that were unattainable previously. Comprehensive understanding of the intrinsic properties of 2D materials, approaches and capabilities for chemical and physical engineering methods, the resulting property modifications and novel functionalities, and applications of metaphotonic devices are provided in this review. Through reviewing the detailed progress in each aspect and the state-of-the-art achievement, insightful analyses of the outstanding challenges and future directions are elucidated in this cross-disciplinary comprehensive review with the aim to provide an overall development picture in the field of 2D material metaphotonics and promote rapid progress in this fast emerging and prosperous field.

Mac-2-Binding Protein Glycosylation Isomer to Albumin Ratio Predicts Bacterial Infections in Cirrhotic Patients.

INTRODUCTION: Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel biomarker for liver fibrosis, but little is known about its role in cirrhosis-associated clinical outcomes. This study aimed to investigate the predictive role of M2BPGi in cirrhosis-associated complications. METHODS: One hundred and forty-nine cirrhotic patients were retrospectively enrolled. Patients were followed up for 1 year, and cirrhosis-associated clinical events were recorded. Receiver operating characteristic curve (ROC) analysis was used to establish the values of the predictive models for cirrhotic outcomes, and Cox proportional hazards regression models were used to identify predictors of clinical outcomes. RESULTS: Sixty (40.3%) patients experienced cirrhosis-associated clinical events and had higher M2BPGi levels compared to those without events (8.7 vs. 5.1 cutoff index, p < 0.001). The most common cirrhosis-associated complications were bacterial infections (24.2%). On ROC analysis, M2BPGi to albumin ratio (M2BPGi/albumin) had comparable discriminant abilities for all cirrhosis-associated events (area under the ROC curve [AUC] = 0.74) compared with M2BPGi, Child-Pugh, model for end-stage liver disease, albumin-bilirubin scores, and neutrophil-to-lymphocyte ratio and was superior to M2BPGi alone for all bacterial infectious events (AUC = 0.80). Cox regression analysis revealed that the M2BPGi/albumin, but not M2BPGi alone, independently predicted all cirrhosis-associated events (hazard ratio [HR] = 1.34, p = 0.038) and all bacterial infectious events (HR = 1.51, p = 0.011) within 1 year. However, M2BPGi/albumin did not predict other cirrhotic complications and transplant-free survival. DISCUSSION/CONCLUSION: M2BPGi/albumin might serve as a potential prognostic indicator for patients with cirrhosis, particularly for predicting bacterial infections.

Phase III clinical trial comparing the efficacy and safety of adamgammadex with sugammadex for reversal of rocuronium-induced neuromuscular block.

BACKGROUND: Preliminary clinical trials of adamgammadex, a new cyclodextrin-based selective reversal agent, have demonstrated its efficacy in reversing neuromuscular block by rocuronium. METHODS: This multicentre, randomised, double-blind, positive-controlled, non-inferiority phase III clinical trial compared the efficacy and safety of adamgammadex and sugammadex. We randomised 310 subjects to receive adamgammadex (4 mg kg-1) or sugammadex (2 mg kg-1) at reappearance of the second twitch of the train-of-four (TOF), and standard safety data were collected. RESULTS: For the primary outcome, the proportion of patients with TOF ratio ≥0.9 within 5 min was 98.7% in the adamgammadex group vs 100% in the sugammadex group, with a point estimate and 95% confidence interval (CI) of 1.3% (-4.6%, +1.3%); the lower limit was greater than the non-inferiority margin of -10%. For the key secondary outcome, the median (inter quartile range) time from the start of administration of adamgammadex or sugammadex to recovery of TOF ratio to 0.9 was 2.25 (1.75, 2.75) min and 1.75 (1.50, 2.00) min, respectively. The difference was 0.50 (95% CI: 0.25, 0.50); the upper limit was lower than the non-inferiority margin of 5 min. In addition, there were no inferior results observed in secondary outcomes. Adamgammadex had a lower incidence of adverse drug reactions compared with sugammadex (anaphylactic reaction, recurarisation, decreased heart rate, and laryngospasm; P=0.047). CONCLUSIONS: Adamgammadex was non-inferior to sugammadex with a possible lower incidence of adverse drug reactions compared with sugammadex. Adamgammadex may have a potential advantage in terms of its overall risk-benefit profile. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000039525. Registered October 30, 2020. https://www.chictr.org.cn/showproj.html?proj=56825.

Extramammary Paget's Disease of the Scrotal and Penile: A Case Report and Review of the Literature.

INTRODUCTION: Extramammary Paget's disease of the scrotum and penis is a relatively rare cutaneous malignant tumor. At present, its pathogenesis, and clinical and pathological characteristics are not very clear. This is controversial regarding surgical margin width to decrease the high recurrence rate. This paper aimed to report the case and review the literature of extramammary Paget's disease of scrotum and penis. CASE PRESENTATION: We presented the case of a 74-year-old male patient with the patchy erythema and pruritus in the perineum who was admitted to our department. Biopsy of the large plaque revealed Paget disease. Under the condition of ensuring negative surgical margins by rapid frozen pathology, a wide local excision of the lesion, bilateral orchiectomy, and adnexectomy were performed on the patient. Pathology revealed that many scattered vacuolated Paget cells were observed in the epidermal layer, and the diagnosis was Paget's disease of the scrotum and penis. The 2 cm outside the skin lesion was used as the initial surgical margin, and free skin flap transplantation was used to repair the surgical wound. The patient recovered well and was discharged 1 week after surgery. CONCLUSION: Currently, histopathologic biopsy is the most important diagnostic method for EMPD. Once confirmed, for patients eligible for surgical intervention, wide local excision of the lesion and rapid intraoperative frozen pathological examination should be performed as soon as possible. The skin flap transplantation is the first choice for the repair of large-scale wound after surgery.

Genome and whole-genome resequencing of Cinnamomum camphora elucidate its dominance in subtropical urban landscapes.

BACKGROUND: Lauraceae is well known for its significant phylogenetic position as well as important economic and ornamental value; however, most evergreen species in Lauraceae are restricted to tropical regions. In contrast, camphor tree (Cinnamomum camphora) is the most dominant evergreen broadleaved tree in subtropical urban landscapes. RESULTS: Here, we present a high-quality reference genome of C. camphora and conduct comparative genomics between C. camphora and C. kanehirae. Our findings demonstrated the significance of key genes in circadian rhythms and phenylpropanoid metabolism in enhancing cold response, and terpene synthases (TPSs) improved defence response with tandem duplication and gene cluster formation in C. camphora. Additionally, the first comprehensive catalogue of C. camphora based on whole-genome resequencing of 75 accessions was constructed, which confirmed the crucial roles of the above pathways and revealed candidate genes under selection in more popular C. camphora, and indicated that enhancing environmental adaptation is the primary force driving C. camphora breeding and dominance. CONCLUSIONS: These results decipher the dominance of C. camphora in subtropical urban landscapes and provide abundant genomic resources for enlarging the application scopes of evergreen broadleaved trees.

Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with impaired renal function, and both diseases often occur alongside other metabolic disorders. However, the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear. The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients. METHODS: All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study. Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase (FAST), Agile 3+ and Agile 4 scores. Impaired renal function and chronic kidney disease (CKD) were defined by an estimated glomerular filtration rate (eGFR) with value of < 90 mL/min/1.73 m2 and < 60 mL/min/1.73 m2, respectively, as estimated by the CKD-Epidemiology Collaboration (CKD-EPI) equation. RESULTS: Among 529 included NAFLD patients, the prevalence rates of impaired renal function and CKD were 37.4% and 4.9%, respectively. In multivariate analysis, a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+ and Agile 4 scores were independent risk factors for CKD (P< 0.05). Furthermore, increased fasting plasma glucose (FPG) and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome (P< 0.05). Compared with patients with normoglycemia, those with prediabetes [FPG ≥ 5.6 mmol/L or hemoglobin A1c (HbA1c) ≥ 5.7%] were more likely to have impaired renal function (P< 0.05). CONCLUSIONS: Agile 3+ and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD. Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

Does the diagnostic timing of cancer-associated thromboembolism influence the survival outcome in ovarian cancer patients?

BACKGROUND/PURPOSE: Efforts were made to explore the influence of diagnostic timing for cancer-associated thromboembolic events on survival of ovarian cancer patients. METHODS: We reviewed the medical records of 75 ovarian cancer patients with thromboembolism and evaluated the prognostic factors affecting disease-free survival and overall survival. RESULTS: These 75 patients were classified into two categories by the diagnostic timing of the thromboembolism, during (33 cases) and after (42 cases) initial diagnosis of ovarian cancer groups. The diagnostic timing of thromboembolism was not related to disease-free survival or overall survival of the studied population. Advanced disease stage, clear cell histology, interval debulking surgery, no recurrence/persistence of ovarian cancer, and patients treated with anticoagulant(s) treatment >3 months were associated with the disease-free survival. Advanced disease stage, clear cell histology, body mass index (BMI) ≥24 kg/m2 at the diagnosis of ovarian cancer, and no recurrence/persistence of ovarian cancer influenced the overall survival. In the subgroup analysis, compared to the after initial ovarian cancer diagnosis group, patients with stage I/II disease, BMI <24 kg/m2 at the diagnosis of ovarian cancer, or primary debulking surgery in the during cancer diagnosis group had longer disease-free survival, and overall survival benefit was observed in cases with stage I/II disease, or primary debulking surgery. CONCLUSION: The diagnostic timing of thromboembolism was not related to disease-free or overall survival of ovarian cancer patients, but associated with that of specific patient subgroups.