Size-dependent influences of nano- and micro-plastics exposure on feeding, antioxidant systems, and organic sulfur compounds in ciliate Uronema marinum.

Protozoa play a pivotal role in the microbial cycle, and ciliated protozoan grazing habits are associated with dimethyl sulfide (DMS) cycle. Many studies have explored the impacts of nanoplastics (NPs) and microplastics (MPs) on ecotoxicological effects of ciliates. However, limited research exists on NPs and MPs influences on the production of organic sulfur compounds. The impact of NPs and MPs on the production of dimethyl sulfoxide (DMSO) and carbonyl sulfide (COS) remains unclear. Therefore, we examined the impacts of three concentrations (1 × 105, 5 × 105, and 1 × 106 items/mL) of polystyrene (PS) NPs (50 nm) and MPs (1 and 5 µm) on the ecotoxicology and DMS/dimethylsulfoniopropionate (DMSP)/DMSO/COS production in the ciliate Uronema marinum. NPs and MPs exposure were found to reduce the abundance, growth rate, volume, and biomass of U. marinum. Additionally, NPs and MPs increased the superoxide anion radical (O2˙─) production rates and malondialdehyde (MDA) contents (24 h), leading to a decline in glutathione (GSH) content and an ascend in superoxide dismutase (SOD) activity to mitigate the effects of reactive oxygen species (ROS). Exposure to PS NPs and MPs decreased the ingestion rates of algae by 7.5-14.4%, resulting in decreases in DMS production by 56.8-85.4%, with no significant impact on DMSO production. The results suggest a distinct pathway for the production of DMSO or COS compared to DMS. These findings help us to understand the NPs and MPs impacts on the marine ecosystem and organic sulfur compound yield, potentially influencing the global climate.

Genetic background and intraoperative haemodynamic instability in patients with pheochromocytoma and paraganglioma: a multicenter retrospective study.

BACKGROUND: Perioperative management to maintain intraoperative haemodynamic stability is crucial during surgical treatment of pheochromocytomas and paragangliomas (PPGLs). Although approximately 70% of PPGLs carry pathogenic variants (PVs) in susceptibility genes, whether intraoperative haemodynamic instability (IHI) is associated with genetic background remains unclear. This study aimed to analyse IHI in patients with PPGL due to PVs in different genes. MATERIALS AND METHODS: This retrospective study recruited 756 patients with abdominal PPGL from two tertiary care centres. Clinical information including sex, age, catecholamine-associated signs and symptoms (CAS), tumour location and size, biochemistry, and perioperative characteristics were collected. Genetic mutations were investigated using next-generation sequencing. RESULTS: Among the 671 patients included in the analysis, 61.8% (415/671) had IHI. IHI was significantly associated with genetic background in patients with PPGL. Most (80.9%, 89/110) patients with PPGL due to PVs in HRAS suffered IHI. In contrast, only half (31/62) of patients with PPGL due to PVs in VHL had IHI. In the multivariate regression analysis, compared to those with negative genetic testing results, patients with PPGL due to PVs in HRAS (OR 3.82, 95% CI 2.187-6.679, P<0.001), the other cluster 2 genes (OR 1.95, 95% CI 1.287-2. 569, P< 0.05), and cluster 1 genes other than VHL (OR 2.35, 95% CI 1.338-4.111, P<0.05) were independent risk factors for IHI, while PVs in VHL was not independent risk factor (OR 1.09, 95% CI 0.605-1.953, P>=0.05). In addition, age at diagnosis of primary tumour, presenting of CAS, and tumour size were identified as independent factors for IHI. The nomogram illustrated that genetic background as sharing the largest contribution to IHI, followed by tumour size, age, and presenting of CAS. CONCLUSION: IHI is associated with the genetic background in patients with PPGL. The perioperative management of patients with PPGL can be personalized according to their genetic backgrounds, tumour size, age, and presenting of CAS.

Impacts of nano- and micro-plastics exposure on zooplankton grazing, bacterial communities, and dimethylated sulfur compounds production in the microcosms.

Dimethyl sulfide (DMS) is a prevalent volatile organic sulfur compound relevant to the global climate. Ecotoxicological effects of nano- and microplastics (NPs and MPs) on phytoplankton, zooplankton, and bacteria have been investigated by numerous studies. Yet, the influences of NPs/MPs on dimethylated sulfur compounds remains understudied. Herein, we investigated the impacts of polystyrene (PS) NPs/MPs (80 nm, 1 µm, and 10 µm) on zooplankton grazing, chlorophyll a (Chl a) concentration, bacterial community, dimethylsulfoniopropionate (DMSP), and DMS production in the microcosms. Our findings revealed that rotifer grazing increased the production of DMS in the absence of NPs/MPs but did not promote DMS production when exposed to NPs/MPs. The ingestion rates of the rotifer and copepod exposed to NPs/MPs at high concentrations were significantly reduced. NPs/MPs exposure significantly decreased DMS levels in the treatments with rotifers compared to the animal controls. In the bacterial microcosms, smaller NPs/MPs sizes were more detrimental to Chl a concentrations compared to larger sizes. The study revealed a stimulatory effect on Chl a concentrations, DMSPd concentrations, and bacterial abundances when exposed to 10 µm MP with low concentrations. The effects of NPs/MPs on DMS concentrations were both dose- and size-dependent, with NPs showing greater toxicity compared to larger MPs. NPs/MPs led to changes in bacterial community compositions, dependent on both dosage and size. NPs caused a notable decrease in the alpha diversities and richness of bacteria compared to MPs. These results provide insights into the influences of NPs/MPs on food webs, and subsequently organic sulfur compounds cycles.

Photocatalytic Multisite Functionalization of Unactivated Terminal Alkenes by Merging Polar Cycloaddition and Radical Ring-Opening Process.

Although highly appealing for rapid access of molecular complexity, multi-functionalization of alkenes that allows incorporation of more than two functional groups remains a prominent challenge. Herein, we report a novel strategy that merges dipolar cycloaddition with photoredox promoted radical ring-opening remote C(sp3)-H functionalization, thus enabling a smooth 1,2,5-trifunctionalization of unactivated alkenes. A highly regioselective [3+2] cycloaddition anchors a reaction trigger onto alkene substrates. The subsequent halogen atom transfer (XAT) selectively initiates ring-opening process, which is followed by a series of 1,5-hydrogen atom transfer (1,5-HAT) and intermolecular fluorine atom transfer (FAT) events. With this method, site-selective introduction of three different functional groups is accomplished and a broad spectrum of valuable ß-hydroxyl-ε-fluoro-nitrile products are synthesized from readily available terminal alkenes.

Controllable preparation of graphene glass fiber fabric towards mass production and its application in self-adaptive thermal management.

Direct synthesis of graphene on nonmetallic substrates via chemical vapor deposition (CVD) has become a frontier research realm targeting transfer-free applications of CVD graphene. However, the stable mass production of graphene with a favorable growth rate and quality remains a grand challenge. Herein, graphene glass fiber fabric (GGFF) was successfully developed through the controllable growth of graphene on non-catalytic glass fiber fabric, employing a synergistic binary-precursor CVD strategy to alleviate the dilemma between growth rate and quality. The binary precursors consisted of acetylene and acetone, where acetylene with high decomposition efficiency fed rapid graphene growth while oxygen-containing acetone was adopted for improving the layer uniformity and quality. Notably, the bifurcating introducing-confluent premixing (BI-CP) system was self-built for the controllable introduction of gas and liquid precursors, enabling the stable production of GGFF. GGFF features solar absorption and infrared emission properties, based on which the self-adaptive dual-mode thermal management film was developed. This film can automatically switch between heating and cooling modes by spontaneously perceiving the temperature, achieving excellent thermal management performances with heating and cooling power of ∼501.2 and ∼108.6 W m-2, respectively. These findings unlock a new strategy for the large-scale batch production of graphene materials and inspire advanced possibilities for further applications.

LDSG-Net: an efficient lightweight convolutional neural network for acute hypotensive episode prediction during ICU hospitalization.

Objective. Acute hypotension episode (AHE) is one of the most critical complications in intensive care unit (ICU). A timely and precise AHE prediction system can provide clinicians with sufficient time to respond with proper therapeutic measures, playing a crucial role in saving patients' lives. Recent studies have focused on utilizing more complex models to improve predictive performance. However, these models are not suitable for clinical application due to limited computing resources for bedside monitors.Approach. To address this challenge, we propose an efficient lightweight dilated shuffle group network. It effectively incorporates shuffling operations into grouped convolutions on the channel and dilated convolutions on the temporal dimension, enhancing global and local feature extraction while reducing computational load.Main results. Our benchmarking experiments on the MIMIC-III and VitalDB datasets, comprising 6036 samples from 1304 patients and 2958 samples from 1047 patients, respectively, demonstrate that our model outperforms other state-of-the-art lightweight CNNs in terms of balancing parameters and computational complexity. Additionally, we discovered that the utilization of multiple physiological signals significantly improves the performance of AHE prediction. External validation on the MIMIC-IV dataset confirmed our findings, with prediction accuracy for AHE 5 min prior reaching 93.04% and 92.04% on the MIMIC-III and VitalDB datasets, respectively, and 89.47% in external verification.Significance. Our study demonstrates the potential of lightweight CNN architectures in clinical applications, providing a promising solution for real-time AHE prediction under resource constraints in ICU settings, thereby marking a significant step forward in improving patient care.

Effects of micro- and nano-plastics on growth, antioxidant system, DMS, and DMSP production in Emiliania huxleyi.

Due to the potential impacts of microplastics (MPs) and nanoplastics (NPs) on algal growth and thereby affect the climate-relevant substances, dimethylsulfoniopropionate (DMSP) and dimethyl sulfide (DMS), we studied the polystyrene (PS) MPs and NPs of 1 µm and 80 nm impacts on the growth, chlorophyll content, reactive oxygen species (ROS), antioxidant enzyme activity, and DMS/DMSP production in Emiliania huxleyi. E. huxleyi is a prominent oceanic alga that plays a key role in DMS and DMSP production. The results revealed that high concentrations of MPs and NPs inhibited the growth, carotenoid (Car), and Chl a concentrations of E. huxleyi. However, short-time exposure to low concentrations of PS MPs and NPs stimulated the growth of E. huxleyi. Furthermore, high concentrations of MPs and NPs resulted in an increase in the superoxide anion radical (O2.-) production rate and a decrease in the malondialdehyde (MDA) content compared with the low concentrations. Exposure to MPs and NPs at 5 mg L-1 induced superoxide dismutase (SOD) activity as a response to scavenging ROS. High concentrations of MPs and NPs significantly inhibited the production of DMSP and DMS. The findings of this study support the potential ecotoxicological impacts of MPs and NPs on algal growth, antioxidant system, and dimethylated sulfur compounds production, which maybe potentially impact the global climate.

Analysis of functional connectivity changes in attention networks and default mode networks in patients with depression and insomnia.

PURPOSE: Major Depressive Disorder (MDD) and Insomnia Disorder (ID) are prevalent psychiatric conditions often occurring concurrently, leading to substantial impairment in daily functioning. Understanding the neurobiological underpinnings of these disorders and their comorbidity is crucial for developing effective interventions. This study aims to analyze changes in functional connectivity within attention networks and default mode networks in patients with depression and insomnia. METHODS: The functional connectivity alterations in individuals with MDD, ID, comorbid MDD and insomnia (iMDD), and healthy controls (HC) were assessed from a cohort of 174 participants. They underwent rs-fMRI scans, demographic assessments, and scale evaluations for depression and sleep quality. Functional connectivity analysis was conducted using region-of-interest (ROI) and whole-brain methods. RESULTS: The MDD and iMDD groups exhibited higher Hamilton Depression Scale (HAMD) scores compared to HC and ID groups (P < 0.001). Both ID and MDD groups displayed enhanced connectivity between the left and right orbital frontal cortex compared to HC (P < 0.05), while the iMDD group showed reduced connectivity compared to HC and ID groups (P < 0.05). In the left insula, reduced connectivity with the right medial superior frontal gyrus was observed across patient groups compared to HC (P < 0.05), with the iMDD group showing increased connectivity compared to MDD (P < 0.05). Moreover, alterations in functional connectivity between the left thalamus and left temporal pole were found in iMDD compared to HC and MDD (P < 0.05). Correlation analyses revealed associations between abnormal connectivity and symptom severity in MDD and ID groups. CONCLUSIONS: Our findings demonstrate distinct patterns of altered functional connectivity in individuals with MDD, ID, and iMDD compared to healthy controls. These findings contribute to a better understanding of the pathophysiology of depression and insomnia, which could be used as a reference for the diagnosis and treatments of these patients.

Influence of the community assemblage on sulfur distributions in the South China sea.

Marine distribution of dimethylsulfoniopropionate (DMSP) and its cleavage product dimethyl sulfide (DMS) is greatly affected by the community structures of bacteria, phytoplankton, and zooplankton. Spatial distributions of dissolved and particulate DMSP (DMSPd,p), and DMS were measured and their relationships with DMSP lyase activity (DLA), abundance of DMSP-consuming bacteria (DCB), and the community structures of phytoplankton, zooplankton, and bacteria were determined during summer in the South China Sea (SCS). The depth distributions of DMSPd,p exhibited a similar trend with Chl a, reaching their maxima in the mixing layer. The DMS concentration was positively correlated with DCB abundance and DLA, indicating that DCB and DMSP lyase had a significant effect on DMS production. High DMS concentrations in the horizontal distribution coincided with high DCB abundance and DLA and may be due to the rapid growth of phytoplankton resulting from the high dissolved inorganic nitrogen concentration brought by the cold vortices. Moreover, the highest copepod abundance at station G3 coincided with the highest DMS concentrations there among stations B4, F2, and G3. These results suggest that copepod may play an important role in DMS production. The bacterial SAR11 clade was positively correlated with DLA, indicating its significant contribution to DMSP degradation in the SCS. These findings contribute to the understanding of the effect of the community assemblage on DMSP/DMS distributions in the SCS dominated by mesoscale vortices.

Design, synthesis and application of dual-channel fluorescent probes for ratiometric detection of HClO and H2S based on phenothiazine coumarins.

The ubiquity of diverse material entities in environmental matrices renders the deployment of unifunctional fluorescent indicators inadequate. Consequently, this study introduces a ratiometric dual-emission fluorescent sensor (Probe CP), synthesized by conjugating phenothiazine coumarin to hydroxycoumarin through a piperazine linker for concurrent detection of HClO and H2S. Upon interaction with HClO, the phenothiazine unit's sulfur atom undergoes oxidation to sulfoxide, facilitating a shift from red to green fluorescence in a ratiometric manner. Concurrently, at the opposite terminus of Probe CP, 2,4-dinitroanisole serves as the reactive moiety for H2S recognition; it restores the blue emission characteristic of 7-hydroxycoumarin while maintaining the red fluorescence emanating from phenothiazine coumarin as an internal standard for ratio-based assessment. Exhibiting elevated specificity and sensitivity coupled with minimal detection thresholds (0.0506 µM for HClO and 1.7292 µM for H2S) alongside rapid equilibration periods (3 min for HClO and half an hour for H2S), this sensor was efficaciously employed in cellular environments and within zebrafish models as well as imaging applications pertaining to alcohol-induced hepatic injury in murine subjects.

Diagnosis and management of urinary bladder paragangliomas: A Sino-American-European retrospective observational study.

OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.

Diosgenin improves post-myocardial infarction cardiac function via HAND2-induced angiogenesis.

While diosgenin has been demonstrated effective in various cardiovascular diseases, its specific impact on treating heart attacks remains unclear. Our research revealed that diosgenin significantly improved cardiac function in a myocardial infarction (MI) mouse model, reducing cardiac fibrosis and cell apoptosis while promoting angiogenesis. Mechanistically, diosgenin upregulated the Hand2 expression, promoting the proliferation and migration of endothelial cells under hypoxic conditions. Acting as a transcription factor, HAND2 activated the angiogenesis-related gene Aggf1. Conversely, silencing Hand2 inhibited the diosgenin-induced migration of hypoxic endothelial cells and angiogenesis. In summary, these findings provide new insights into the protective role of diosgenin in MI, validating its effect on angiogenic activity and providing a theoretical basis for clinical treatment strategies.

Emerging Therapeutic Approaches Targeting Ferroptosis in Cancer: Focus on Immunotherapy and Nanotechnology.

Ferroptosis is a newly discovered form of programmed cell death characterized by iron overload, ROS accumulation, and lipid peroxidation. It is distinguished by unique morphological, biochemical, and genetic features and stands apart from other known regulated cell death mechanisms. Studies have demonstrated a close association between ferroptosis and various cancers, including liver cancer, lung cancer, renal cell carcinoma, colorectal cancer, pancreatic cancer, and ovarian cancer. Inducing ferroptosis has shown promising results in inhibiting tumor growth and reversing tumor progression. However, the challenge lies in regulating ferroptosis in vivo due to the scarcity of potent compounds that can activate it. Integrating emerging biomedical discoveries and technological innovations with conventional therapies is imperative. Notably, considerable progress has been made in cancer treatment by leveraging immunotherapy and nanotechnology to trigger ferroptosis. This review explores the relationship between ferroptosis and emerging immunotherapies and nanotechnologies, along with their potential underlying mechanisms, offering valuable insights for developing novel cancer treatment strategies.

[Retracted] microRNA­195 inhibits cell proliferation in bladder cancer via inhibition of cell division control protein 42 homolog/signal transducer and activator of transcription­3 signaling.

[This retracts the article DOI: 10.3892/etm.2015.2633.].

Effects of nanoplastics exposure on ingestion, life history traits, and dimethyl sulfide production in rotifer Brachionus plicatilis.

Microplastics (MPs) and nanoplastics (NPs) have gained global concern due to their detrimental effects on marine organisms. We investigated the effects of 80 nm polystyrene (PS) NPs on life history traits, ingestion, and dimethyl sulfide (DMS) and dimethylsulfoniopropionate (DMSP) production in the rotifer Brachionus plicatilis. Fluorescently labeled 80 nm PS NPs were ingested by the rotifer B. plicatilis and accumulated in the digestive tract. The lethal rates of B. plicatilis exposed to NPs were dose-dependent. High concentrations of PS NPs exposure had negative effects on developmental duration, leading to prolonged embryonic development and pre-reproductive periods, shortened reproductive period, post-reproductive period, and lifespan in B. plicatilis. High concentrations of PS NPs exposure inhibited life table demographic parameters such as age-specific survivorship and fecundity, generation time, net reproductive rate, and life expectancy. Consequently, the population of B. plicatilis was adversely impacted. Furthermore, exposure to PS NPs resulted in a reduced ingestion rate in B. plicatilis, as well as a decreased in DMS, particulate DMSP (DMSPp) concentration, and DMSP lyase activity (DLA), which exhibited a dose-response relationship. B. plicatilis grazing promoted DLA and therefore increased DMS production. PS NPs exposure caused a decline in the increased DMS induced by rotifer grazing. Our results help to understand the ecotoxicity of NPs on rotifer and their impact on the biogeochemical cycle of dimethylated sulfur compounds.

Remobilization of Cd caused by iron oxide phase transformation and Mn2+ competition after stabilization by nano zero valent iron.

Stabilization techniques are vital in controlling Cd soil pollution. Nano zero valent iron (nZVI) has been extensively utilized for Cd remediation owing to its robust adsorption and reactivity. However, the environmental stress-induced stability of Cd after nZVI addition remains unclear. A pot experiment was conducted to evaluate the Cd bioavailability in continuously flooded (130 d) soil after stabilization with nZVI. The findings indicated that nZVI application did not result in a decline in Cd concentration in rice, as compared to the no-nZVI control. Additionally, nZVI simultaneously increased the available Cd concentration, iron-manganese oxide-bound (OX) Mn fraction, and relative abundance of Fe(III)-reducing bacteria, but it decreased OX-Cd and Mn availability in soil. Cadmium in rice tissues was positively correlated with the available Cd in soil. The results of subsequent adsorption tests demonstrated that CdO was the product of Cd adsorption by the nZVI aging products. Conversely, Mn2+ decreased the adsorption capacity of Cd-containing solutions. These results underscore the crucial role of both biotic and abiotic factors in undermining the stabilization of nZVI under continuous flooding conditions. This study offers novel insights into the regulation of nZVI-mediated Cd stabilization efficiency in conjunction with biological inhibitors and functional modification techniques.

ERK1/2-dependent activity of SOX9 is required for sublytic C5b-9-induced expression of FGF1, PDGFα, and TGF-ß1 in rat Thy-1 nephritis.

Mesangial proliferative glomerulonephritis (MsPGN) and its related rat model Thy-1 nephritis (Thy-1N) are associated with C5b-9 deposition and are characterized by proliferation of glomerular mesangial cell (GMC) and expansion of extracellular matrix (ECM) expansion, alongside overexpression of multiple growth factors. Although fibroblast growth factor 1 (FGF1), platelet-derived growth factor alpha (PDGFα), and transforming growth factor beta 1 (TGF-ß1) are well known for their proproliferative and profibrotic roles, the molecular mechanisms responsible for regulating the expression of these growth factors have not been thoroughly elucidated. In this study, we found that sublytic C5b-9 induction of sex-determining region Y-box 9 (SOX9) transactivated FGF1, PDGFα, and TGF-ß1 genes in GMCs, resulting in a significant increase in their mRNA and protein levels. Besides, sublytic C5b-9 induction of activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylated SOX9 at serine 181 and serine 64, which enhanced SOX9's ability to transactivate FGF1, PDGFα, and TGF-ß1 genes in GMCs. Furthermore, we demonstrated that inhibiting ERK1/2 activation or silencing either ERK1/2 or SOX9 gene led to reduced SOX9 phosphorylation, decreased generation of FGF1, PDGFα, and TGF-ß1, and ameliorated glomerular injury in rat Thy-1N. Overall, these findings suggest that expression of FGF1, PDGFα, and TGF-ß1 is promoted by ERK1/2-mediated phosphorylation of SOX9, which may provide a valuable insight into the pathogenesis of MsPGN and offer a potential target for the development of novel treatment strategies for MsPGN.

A novel proline-rich M-superfamily conotoxin that can simultaneously affect sodium, potassium and calcium currents

Background Conotoxins have become a research hotspot in the neuropharmacology field for their high activity and specificity in targeting ion channels and neurotransmitter receptors. There have been reports of a conotoxin acting on two ion channels, but rare reports of a conotoxin acting on three ion channels. Methods Vr3a, a proline-rich M-superfamily conotoxin from a worm-hunting Conus varius, was obtained by solid-phase synthesis and identified by mass spectrometry. The effects of synthesized Vr3a on sodium, potassium and calcium currents were tested on rat DRG cells by patch clamp experiments. The further effects of Vr3a on human Cav1.2 and Cav2.2 currents were tested on HEK293 cells. Results About 10 μM Vr3a has no effects on the peak sodium currents, but can induce a ~10 mV shift in a polarizing direction in the current-voltage relationship. In addition, 10 μM Vr3a can increase 19.61 ± 5.12% of the peak potassium currents and do not induce a shift in the current-voltage relationship. An amount of 10 μM Vr3a can inhibit 31.26% ± 4.53% of the peak calcium currents and do not induce a shift in the current-voltage relationship. The IC50 value of Vr3a on calcium channel currents in rat DRG neurons is 19.28 ± 4.32 μM. Moreover, 10 μM Vr3a can inhibit 15.32% ± 5.41% of the human Cav1.2 currents and 12.86% ± 4.93% of the human Cav2.2 currents. Conclusions Vr3a can simultaneously affect sodium, potassium and calcium currents. This novel triple-target conotoxin Vr3a expands understanding of conotoxin functions.(AU)

Localized chromophobe renal cell carcinoma: preoperative imaging judgment and laparoscopic simple enucleation for treatment

ABSTRACT Objective: To evaluate the preoperative imaging manifestation and therapeutic effect of laparoscopic simple enucleation (SE) for localized chromophobe renal cell carcinoma (chRCC). Materials and Methods: Clinical data of 36 patients who underwent laparoscopic SE of localized chRCC at our institute were retrospectively analyzed. All patients underwent preoperative renal protocol CT (unenhanced, arterial, venous, and delayed images). CT scan characteristics were evaluated. After intraoperative occlusion of the renal artery, the tumor was free bluntly along the pseudocapsule and enucleated totally. The patients were followed up regularly after the operation. Results: Mean tumor diameter was 3.9±1.0 cm, 80% of tumors were homogeneous and all the tumors had complete pseudocapsule. The attenuation values were slightly lower than normal renal cortex and degree of enhancement of the tumors were significantly lower than normal renal cortex. Mean operation time was 104.3±18.2 min. Mean warm ischemia time (WIT) was 21.3±3.5 min. Mean blood loss was 78.6±25.4 mL. No positive surgical margin was identified. Mean postoperative hospital stay was 5.3±1.5 d. Hematuria occurred in 3 patients and all disappeared within 3 days. After a mean follow-up of 32.1±20.6 months, no patient had local recurrence or metastatic progression. Conclusion: Localized chRCCs have a great propensity for homogeneity and complete pseudocapsule. The attenuation values were slightly lower than normal renal cortex and small degree of enhancement. Laparoscopic SE is a safe and effective treatment for localized chRCC. The oncological results were satisfactory.