Radiofrequency ablation with sine and square electrical waveforms to enhance ablation range.

Radiofrequency ablation (RFA) is a local treatment modality for primary liver cancers. Although various input parameters of the RF generator have been adjusted to improve the ablation ranges, the limited ablation ranges remain an obstacle to RFA. This study aimed to compare the ablation ranges and efficacy of sine and square electrical waveforms in a mouse tumor model. An RF generator with an adjustable electrical waveform was developed, and its ablation range in the porcine liver was compared. For all RF parameters, the square electrical waveform ablation range was greater than that of the sine electrical waveform (all p < 0.001) in the porcine liver. The 45 BALB/c nude mice were used to evaluate the efficacy of the two electrical waveforms after the RFA. The mean tumor volume in the square group was significantly lower than that in the sine group (p < 0.001), indicating a higher survival rate (60%). The cellular coagulative necrosis, inflammatory cell infiltration, heat shock proteins, cellular necrosis, and tumor necrosis were significantly greater in square electrical waveform than in sine electrical waveform (all; p < 0.05). RFA with square electrical waveforms has therapeutic potential for tumor management with an enhanced ablation range.

The changing scenario of drug discovery using AI to deep learning: Recent advancement, success stories, collaborations, and challenges.

Due to the transformation of artificial intelligence (AI) tools and technologies, AI-driven drug discovery has come to the forefront. It reduces the time and expenditure. Due to these advantages, pharmaceutical industries are concentrating on AI-driven drug discovery. Several drug molecules have been discovered using AI-based techniques and tools, and several newly AI-discovered drug molecules have already entered clinical trials. In this review, we first present the data and their resources in the pharmaceutical sector for AI-driven drug discovery and illustrated some significant algorithms or techniques used for AI and ML which are used in this field. We gave an overview of the deep neural network (NN) models and compared them with artificial NNs. Then, we illustrate the recent advancement of the landscape of drug discovery using AI to deep learning, such as the identification of drug targets, prediction of their structure, estimation of drug-target interaction, estimation of drug-target binding affinity, design of de novo drug, prediction of drug toxicity, estimation of absorption, distribution, metabolism, excretion, toxicity; and estimation of drug-drug interaction. Moreover, we highlighted the success stories of AI-driven drug discovery and discussed several collaboration and the challenges in this area. The discussions in the article will enrich the pharmaceutical industry.

An amygdalar oscillator coordinates cellular and behavioral rhythms.

Circadian rhythms are generated by the master pacemaker suprachiasmatic nucleus (SCN) in concert with local clocks throughout the body. Although many brain regions exhibit cycling clock gene expression, the identity of a discrete extra-SCN brain oscillator that produces rhythmic behavior has remained elusive. Here, we show that an extra-SCN oscillator in the lateral amygdala (LA) is defined by expression of the clock-output molecule mWAKE/ANKFN1. mWAKE is enriched in the anterior/dorsal LA (adLA), and, strikingly, selective disruption of clock function or excitatory signaling in adLAmWAKE neurons abolishes Period2 (PER2) rhythms throughout the LA. mWAKE levels rise at night and promote rhythmic excitability of adLAmWAKE neurons by upregulating Ca2+-activated K+ channel activity specifically at night. adLAmWAKE neurons coordinate rhythmic sensory perception and anxiety in a clock-dependent and WAKE-dependent manner. Together, these data reveal the cellular identity of an extra-SCN brain oscillator and suggest a multi-level hierarchical system organizing molecular and behavioral rhythms.

Potential prognostic value of rheumatoid factor in anti-aquaporin 4-immunoglobin G-positive neuromyelitis optica spectrum disorders.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is the central nervous system demyelinating disease differentiated from multiple sclerosis by the presence of anti-aquaporin 4-antibody (AQP4-ab), which is sometimes accompanied by non-organ-specific autoantibodies. METHODS: We prospectively collected clinical information and profiles of non-organ-specific autoantibodies such as fluorescent antinuclear (FANA), anti-Sjögren's syndrome A (SSA)/Ro, anti-SS B (SSB)/La, anti-neutrophil cytoplasmatic (ANCA), lupus anticoagulant (LA), anti-cardiolipin (ACA), anti-double-stranded DNA (dsDNA), rheumatoid factor (RF), anti-thyroperoxidase, and anti-thyroglobulin antibodies in patients with NMOSD. Clinical characteristics and laboratory findings of patients with NMOSD with or without autoantibodies were analyzed. Cox proportional hazard models were used to identify independent risk factors predicting high disability in patients with NMOSD. RESULTS: A total of 158 patients with NMOSD (Female: Male = 146:12; age, 36.11 ± 14.7) were included. FANA was observed most frequently (33.3 %), followed by anti-SSA (28.6 %), anti-SSB (10.0 %), RF (8.5 %), anti-dsDNA (7.0 %), LA (4.7 %), ACA (4.8 %), and ANCA (2.4 %). High disability (Expanded Disability Status Scale (EDSS) score ≥ 6) was observed more frequently in patients with RF (45.5 %) than in those without RF (14.5 %) (p = 0.02). RF was a significant predictive factor for the high disability (hazard ratio [HR], 3.763; 95 % confidence interval [CI], 1.086-13.038; p = 0.037), age at onset (HR, 1.093; 95 % CI, 1.05-1.14; p ≤0.001), and annual relapse rate (ARR) (HR, 4.212; 95 % CI, 1.867-9.503; p = 0.001). CONCLUSION: Organ-specific and non-organ-specific autoantibodies are frequently observed in Korean patients with AQP4-ab-positive NMOSD. RF may be an independent predictor of high disability, along with age at onset and ARR.

Effect of polydeoxyribonucleotide and polynucleotide on rotator cuff healing and fatty infiltration in a diabetic rat model.

Failure rate after chronic rotator cuff repair is considerably high. Moreover, diabetes mellitus is known as a compromising factor of rotator cuff tear. The effect of Polydeoxyribonucleotide (PDRN) and polynucleotide (PN) on tendon healing and fatty infiltration is unclear as tissue regeneration activator in diabetic state. Therefore, a diabetic rat model with chronic rotator cuff tear was made for mechanical, histologic and blood tests. In the animal study using a diabetic rat cuff repair model, the administration of PDRN and PN increased the load to failure of repaired cuffs and improved tendon healing and decreased fatty infiltration. Also, the plasma levels of vascular endothelial growth factor and fibroblast growth factor were elevated in PDRN and PN administrated groups. We concluded that PDRN and PN appear to boost tendon recovery and reduce the presence of fatty infiltration following cuff repair in diabetic state. Also, PN showed a later onset and a longer duration than PDRN associated with the mean plasma growth factors.

Dynamic Surface Incorporation of Pb2+ Ions at the Actively Dissolving Calcite (104) Surface.

The reaction of dissolved Pb2+ with calcite surfaces at near-equilibrium conditions involves adsorption of Pb2+ and precipitation of secondary heteroepitaxial Pb-carbonate minerals. A more complex behavior is observed under far-from-equilibrium conditions, including strong inhibition of calcite dissolution, development of microtopography, and near-surface incorporation of multiple monolayers (ML) of Pb2+ without precipitation of secondary phases [where 1 ML ≡ 1 Ca/20.2 Å2, the crystallographic site density of the calcite (104) lattice plane]. However, the mechanistic controls governing far-from-equilibrium reactivity are not well understood. Here, we observe the interfacial incorporation of dissolved Pb2+ during the dissolution of calcite (104) surfaces at pH ∼ 3.7 in a flow-through reaction cell, revealing the formation of a ∼1 nm thick Pb-rich calcite layer with a total Pb coverage of ∼1.4 ML. These observations of the sorbed Pb distribution used resonant anomalous X-ray reflectivity, X-ray fluorescence, and nanoinfrared atomic force microscopy. We propose that this altered surface layer represents a novel sorption mode that is stabilized by conditions of sustained disequilibrium. This behavior may significantly impact the transport of dissolved metals during disequilibrium processes occurring in acid mine drainage and subsurface CO2 injection and, if appropriately accounted for, could improve the predictive capability of geochemical reactive-transport models.

Autoantibodies in COVID-19 and Other Viral Diseases: Molecular, Cellular, and Clinical Perspectives.

Autoantibodies are immune system-produced antibodies that wrongly target the body's cells and tissues for attack. The COVID-19 pandemic has made it possible to link autoantibodies to both the severity of pathogenic infection and the emergence of several autoimmune diseases after recovery from the infection. An overview of autoimmune disorders and the function of autoantibodies in COVID-19 and other infectious diseases are discussed in this review article. We also investigated the different categories of autoantibodies found in COVID-19 and other infectious diseases including the potential pathways by which they contribute to the severity of the illness. Additionally, it also highlights the probable connection between vaccine-induced autoantibodies and their adverse outcomes. The review also discusses the therapeutic perspectives of autoantibodies. This paper advances our knowledge about the intricate interaction between autoantibodies and COVID-19 by thoroughly assessing the most recent findings.

Recent Advances of Nipah Virus Disease: Pathobiology to Treatment and Vaccine Advancement.

The zoonotic infection of the Nipah virus (NiV) has yet again appeared in 2023 in Kerala state, India. The virus, which has a mortality rate ranging from about 40 to 70%, has already infected India five times, the first being in 2001. The current infection is the sixth virus outbreak in the Indian population. In 1998, the first NiV infection was noted in one village in Malaysia. After that, outbreaks from other South and Southeast Asian countries have been reported periodically. It can spread between humans through contact with body fluids. Therefore, it is unlikely to generate a new pandemic. However, there is a considerable knowledge gap in the different areas of NiV. To date, no approved vaccines or treatments have been available. To fulfil the knowledge gap, the review article provided a detailed overview of the genome and genome-encoded proteins, epidemiology, transmission, pathobiology, immunobiology, diagnosis, prevention and control measures, therapeutics (monoclonal antibodies and drug molecules), and vaccine advancement of the emerging and deadly pathogen. The advanced information will help researchers to develop safe and effective NiV vaccine and treatment regimens worldwide.

Efficacy of Fe-Mg-bimetallic biochar in stabilization of multiple heavy metals-contaminated soil and attenuation of toxicity in spinach (Spinacia oleracea L.).

Globally, soil contamination with heavy metals (HMs) pose serious threats to soil health, crop productivity, and human health. The present investigation involved synthesis and analysis of biochar with bimetallic combination of iron and magnesium (Fe-Mg-BC). Our study evaluated how Fe-Mg-BC affects the absorption of cadmium (Cd), lead (Pb), and copper (Cu) in spinach (Spinacia oleracea L.) and remediation of soil contaminated with multiple HMs. Results demonstrated the successful loading of iron (Fe) and magnesium (Mg) onto pristine biochar (BC) derived from peanut shells. The addition of Fe-Mg-BC (3%) notably increased spinach biomass, enhancing photosynthesis, transpiration, stomatal conductance, and intercellular CO2 levels by 22%, 21%, 103%, and 15.3%, respectively. Compared to control, Fe-Mg-BC (3%) suppressed metal-induced oxidative stress by boosting levels of superoxide dismutase (SOD), ascorbate peroxidase (APX) and catalase (CAT) in roots by 40.9%, 57%, 54.8 %, and in shoots by 55.5%, 65.5%, and 37.4% in shoots, respectively. The Fe-Mg-BC effectively reduced the uptake of Cd, Pb, and Cu in spinach tissues by transforming their bioavailable fractions to non-bioavailable forms. The Fe-Mg-BC (3%) significantly reduced the mobility of Cd, Pb and Cu in soil and limited the concentration of Cd, Pb, and Cu in plant roots by 34.1%, 79.2%, 47%, and shoots by 56.3%, 43.3%, and 54.1%, respectively, compared to control. These findings underscore the potential of Fe-Mg-BC as a promising amendment for reclaiming soils contaminated with variety of HMs, thereby making a significant contribution to the promotion of safer food production.

Cryo-EM structure of the human glucose transporter GLUT7.

GLUT7 is a Class II glucose transporter predominantly expressed at the apical membrane of enterocytes in the small intestine. Here, we report the cryo-EM structure of nanodisc-reconstituted human GLUT7 in the apo state at 3.3 Å resolution. Our atomic model reveals a typical major facilitator superfamily fold, with the substrate-binding site open to the extracellular side of the membrane. Despite the nearly identical conformation to its closest family member, rat GLUT5, our structure unveils distinct features of the substrate-binding cavity that may influence substrate specificity and binding mode. A homology model of the inward-open human GLUT7 indicates that similar to other members of the GLUT family, it may undergo a global rocker-switch-like reorientation of the transmembrane bundles to facilitate substrate translocation across the membrane. Our work enhances the current structural understanding of the GLUT family, and lays a foundation for rational design of regulators of GLUTs and other sugar transporters.

Midterm Results after Tibiotalar or Tibiotalocalcaneal Fusion Using an Ilizarov External Fixator.

Background: Ankle fusion is considered a treatment of choice for end-stage ankle arthritis when a total ankle replacement procedure is not indicated. However, the potential risk of secondary arthritis in the adjacent joint after ankle fusion raises arguments on whether preserving the adjacent joint during an isolated tibiotalar (TT) fusion brings about any future benefits with regard to pain and gait discomfort. In this study, we intended to present midterm results following TT or tibiotalocalcaneal (TTC) fusion using an Ilizarov external fixator and to investigate whether spontaneous fusion occurred in the subtalar or midtarsal joint. Methods: This is a retrospective observational study. Medical records of patients who underwent TT or TTC fusion using an Ilizarov external fixator for substantial bone defects around the ankle joint between 1994 and 2018 were manually searched. Forty-one patients were included and the status of the joints adjacent to the fusion site was evaluated in radiographic examinations. Results: Of the 34 patients who underwent TT fusion, 30 patients (88.3%) had a spontaneous fusion in the adjacent joints. Specifically, 11 patients (29.4%) had subtalar joint fusion and 19 patients (55.9%) had both midtarsal joint and subtalar joint fusion. In TTC fusion, the midtarsal joint was spontaneously fused in all 7 patients. Conclusions: In this study, we observed spontaneous adjacent joint fusion following TT or TTC fusion using an Ilizarov external fixator for substantial bone defects around the ankle joint. Although a careful approach should be made since patients treated in this study may not represent typical candidates that need primary joint-sacrificing procedures, we believe that this study may draw attention from surgeons concerned about the fate of the adjacent joint status after TT or TTC fusion.

Etiology and Outcomes of Patients with Extreme Hyperbilirubinemia in Korea: A Retrospective Cohort Study.

Background/Aim: Extreme hyperbilirubinemia is occasionally observed in intensive care unit (ICU) and non-ICU settings. This study examined the etiologies of extreme hyperbilirubinemia (bilirubin level ≥12 mg/dL) and the factors associated with the 30-day mortality. Methods: This retrospective observational cohort study identified 439 patients with extreme hyperbilirubinemia at the Gyeongsang National University Changwon Hospital between 2016 and 2020. The patients were classified into three groups and 11 diseases according to their etiology. The risk factors associated with 30-day mortality at the baseline were investigated using the Cox proportional hazards model. Results: Of 439 patients with extreme hyperbilirubinemia, 287, 78, and 74 were in the liver cirrhosis/malignancy group, the ischemic injury group, and the benign hepatobiliary-pancreatic etiological group, respectively, with corresponding 30-day mortality rates of 42.9%, 76.9%, and 17.6%. The most common disease leading to hyperbilirubinemia was a pancreatobiliary malignancy (28.7%), followed by liver cirrhosis (17.3%), hepatocellular carcinoma (10.9%), and liver metastases (8.4%). The etiologies of hyperbilirubinemia, obstructive jaundice, infection, albumin level, creatinine level, and prothrombin time-international normalized ratio were independently associated with the 30-day mortality. Conclusions: This study suggests three etiologies of extreme hyperbilirubinemia in the ICU and non-ICU settings. The prognosis of patients with extreme hyperbilirubinemia depends largely on the etiology and the presence of obstructive jaundice.

Therapeutic Potential of Quercetin as an Antioxidant for Bone-Muscle-Tendon Regeneration and Aging.

Quercetin (QC), a naturally occurring bioflavonoid found in various fruits and vegetables, possesses many potential health benefits, primarily attributed to its robust antioxidant properties. The generation of oxidative stress in bone cells is a key modulator of their physiological behavior. Moreover, oxidative stress status influences the pathophysiology of mineralized tissues. Increasing scientific evidence demonstrates that manipulating the redox balance in bone cells might be an effective technique for developing bone disease therapies. The QC antioxidant abilities in skeletal muscle significantly enhance muscle regeneration and reduce muscle atrophy. In addition, QC has been shown to have protective effects against oxidative stress, inflammation, apoptosis, and matrix degradation in tendons, helping to maintain the structural integrity and functionality of tendons. Thus, the antioxidant properties of QC might be crucial for addressing age-related musculoskeletal disorders like osteoporosis, sarcopenia, and tendon-related inflammatory conditions. Understanding how QC influences redox signaling pathways involved in musculoskeletal disorders, including their effect on bone, muscle, and tendon differentiation, might provide insights into the diverse advantages of QC in promoting tissue regeneration and preventing cellular damage. Therefore, this study reviewed the intricate relationship among oxidative stress, inflammation, and tissue repair, affected by the antioxidative abilities of QC, in age-related musculoskeletal tissues to improve the overall health of bones, muscles, and tendons of the skeletal system. Also, reviewing the ongoing clinical trials of QC for musculoskeletal systems is encouraging. Given the positive effect of QC on musculoskeletal health, further scientific investigations and controlled human intervention studies are necessary to explore the therapeutic potential to its optimum strength.

Liposomal irinotecan, oxaliplatin, and S-1 as first-line therapy for patients with locally advanced or metastatic pancreatic adenocarcinoma (NASOX): A multicenter phase I/IIa study.

INTRODUCTION: This multicenter phase I/IIa study aimed to determine the recommended phase II dose (RP2D) and evaluate the safety and preliminary efficacy of liposomal irinotecan (nal-IRI), oxaliplatin, and S-1 (NASOX) as first-line treatment for advanced pancreatic adenocarcinoma. METHODS: Patients with locally advanced or metastatic pancreatic adenocarcinoma without prior systemic treatment for advanced disease, aged ≥ 19 years, with measurable disease, and Eastern Cooperative Oncology Group performance status of 0-1 were eligible. The primary endpoints were to determine the dose-limiting toxicity (DLT) in the phase I cohort and overall response rate (ORR) in the phase IIa cohort. The intention-to-treat (ITT) analysis included patients who received the RP2D. RESULTS: In phase I, seven patients were screened, and six were assessed for DLT. None experienced DLT during the first cycle. The RP2D was determined as nal-IRI 50 mg/m2 and oxaliplatin 60 mg/m2 on day 1, S-1 40 mg/m2 twice daily on days 1-7 every 14 days. For the ITT (N = 41; 7, and 34 from phases I and IIa, respectively), the most common grade 3-4 treatment-emergent adverse events were neutropenia (31.7 %), enterocolitis (9.8 %), anorexia (7.3 %), and diarrhea (2.4 %). The ORR was 58.5 % (1 complete, and 23 partial responses). Two underwent conversion surgery; both achieved R0 resection. With median follow-up of 17.5 months, median progression-free survival was 6.5 months (95 % confidence interval [CI], 5.0-8.1) and median overall survival was 11.4 months (95 % CI, 9.8-15.5). CONCLUSION: NASOX exhibited a manageable safety profile and encouraging efficacy outcomes consistent with NALIRIFOX, showing potential to replace infusional 5-fluorouracil with oral S-1 in the triplet regimen.

A field trial for remediation of multi-metal contaminated soils using the combination of fly ash stabilization and Zanthoxylumbungeanum- Lolium perenne intercropping system.

Insitu stabilization and phytoextraction are considered as two convenient and effective technologies for the remediation of toxic elements (TEs) in soils. However, the effectiveness of these two remediation technologies together on the bioavailability and phytoextraction of TEs in field trials has not been explored yet. Specifically, the remediation potential of fly ash (FA; as stabilizing agent) and ryegrass (as a TE accumulator) intercropped with a target crop for soil polluted with multiple TEs has not been investigated yet, particularly in long-term field trials. Therefore, in this study, a six-month combined remediation field experiment of FA stabilization and/or ryegrass intercropping (IR) was carried out on the farmland soils contaminated with As, Cd, Cr, Cu, Hg, Ni, Pb and Zn where Zanthoxylumbungeanum (ZB) trees as native crops were grown for years. The treatments include soil cultivated alone with ZB untreated- (control) and treated-with FA (FA), produced by burning lignite in Shaanxi Datong power plant, China, soil cultivated with ZB and ryegrass untreated- (IR) and treated-with FA (FA + IR). This was underpinned by a large-scale survey in Daiziying (China), which showed that the topsoils were polluted by Cd, Cu, Hg and Pb, and that Hg and Pb contents in the Zanthoxylumbungeanum fruits exceeded their allowable limits. The TEs contents in the studied FA were lower than their total element contents in the soil. The DTPA-extractable TEs contents of the remediation modes were as follows: FA < FA + IR < IR < control. Notably, TEs contents in the ZB fruits were lowest under the FA + IR treatment, which were decreased by 27.6% for As, 42.3% for Cd, 16.7% for Cr, 30.5% for Cu, 23.1% for Hg, 15.5% for Ni, 33.2% for Pb and 38.1% for Zn compared with the control treatment. Whereas the FA + IR treatment enhanced TEs contents in ryegrass shoots and roots, and the TEs contents in ryegrass shoots were below their regulatory limits for fodder crops. The findings confirmed that the combined remediation strategy, i.e., FA (with low content of TEs) stabilization effect and intercropping of ZB (target crop) and ryegrass (accumulating plant) could provide a prospective approach to produce target plants within safe TEs thresholds with greater economic benefits, while remediating soils polluted with multiple TEs and mitigating the potential ecological and human health risk. Those results are of great applicable concern.

Constructed wetlands for the removal of organic micropollutants from wastewater: Current status, progress, and challenges.

In this work, the practical utility of constructed wetlands (CWs) is described as a promising treatment option for micropollutants (MPs) in wastewater with the aid of their eco-friendly, low-energy, economically feasible, and ecologically sustainable nature. This paper offers a comprehensive review on CW technology with respect to the key strategies for MP removal such as phytoremediation, substrate adsorption, and microbial degradation. It explores the important factors controlling the performance of CWs (e.g., in terms of configurations, substrates, plant-microbe interactions, temperature, pH, oxygen levels, hydraulic loading rate, and retention time) along with the discussions on the pivotal role of microbial populations in CWs and plant-microbe cooperative remediation dynamics, particularly in relation to diverse organic MP patterns in CWs. As such, this review aims to provide valuable insights into the key strategies for optimizing MP treatment and for enhancing the efficacy of CW systems. In addition, the process-based models of constructed wetlands along with the numerical simulations based on the artificial neural network (ANN) method are also described in association with the data exploratory techniques. This work is thus expected to help open up new possibilities for the application of plant-microbe cooperative remediation approaches against diverse patterns of organic MPs present in CWs.

Reverse Zoonotic Transmission of SARS-CoV-2 and Monkeypox Virus: A Comprehensive Review.

Reverse zoonosis reveals the process of transmission of a pathogen through the human-animal interface and the spillback of the zoonotic pathogen. In this article, we methodically demonstrate various aspects of reverse zoonosis, with a comprehensive discussion of SARS-CoV-2 and MPXV reverse zoonosis. First, different components of reverse zoonosis, such as humans, different pathogens, and numerous animals (poultry, livestock, pets, wild animals, and zoo animals), have been demonstrated. Second, it explains the present status of reverse zoonosis with different pathogens during previous occurrences of various outbreaks, epidemics, and pandemics. Here, we present 25 examples from literature. Third, using several examples, we comprehensively illustrate the present status of the reverse zoonosis of SARS-CoV-2 and MPXV. Here, we have provided 17 examples of SARS-CoV-2 reverse zoonosis and two examples of MPXV reverse zoonosis. Fourth, we have described two significant aspects of reverse zoonosis: understanding the fundamental aspects of spillback and awareness. These two aspects are required to prevent reverse zoonosis from the current infection with two significant viruses. Finally, the One Health approach was discussed vividly, where we urge scientists from different areas to work collaboratively to solve the issue of reverse zoonosis.

Cryo-EM structure of cadmium-bound human ABCB6.

ATP-binding cassette transporter B6 (ABCB6), a protein essential for heme biosynthesis in mitochondria, also functions as a heavy metal efflux pump. Here, we present cryo-electron microscopy structures of human ABCB6 bound to a cadmium Cd(II) ion in the presence of antioxidant thiol peptides glutathione (GSH) and phytochelatin 2 (PC2) at resolutions of 3.2 and 3.1 Å, respectively. The overall folding of the two structures resembles the inward-facing apo state but with less separation between the two halves of the transporter. Two GSH molecules are symmetrically bound to the Cd(II) ion in a bent conformation, with the central cysteine protruding towards the metal. The N-terminal glutamate and C-terminal glycine of GSH do not directly interact with Cd(II) but contribute to neutralizing positive charges of the binding cavity by forming hydrogen bonds and van der Waals interactions with nearby residues. In the presence of PC2, Cd(II) binding to ABCB6 is similar to that observed with GSH, except that two cysteine residues of each PC2 molecule participate in Cd(II) coordination to form a tetrathiolate. Structural comparison of human ABCB6 and its homologous Atm-type transporters indicate that their distinct substrate specificity might be attributed to variations in the capping residues situated at the top of the substrate-binding cavity.

Coprecipitation of Fe/Cr Hydroxides at Organic-Water Interfaces: Functional Group Richness and (De)protonation Control Amounts and Compositions of Coprecipitates.

Iron/chromium hydroxide coprecipitation controls the fate and transport of toxic chromium (Cr) in many natural and engineered systems. Organic coatings on soil and engineered surfaces are ubiquitous; however, mechanistic controls of these organic coatings over Fe/Cr hydroxide coprecipitation are poorly understood. Here, Fe/Cr hydroxide coprecipitation was conducted on model organic coatings of humic acid (HA), sodium alginate (SA), and bovine serum albumin (BSA). The organics bonded with SiO2 through ligand exchange with carboxyl (-COOH), and the adsorbed amounts and pKa values of -COOH controlled surface charges of coatings. The adsorbed organic films also had different complexation capacities with Fe/Cr ions and Fe/Cr hydroxide particles, resulting in significant differences in both the amount (on HA > SA(-COOH) ≫ BSA(-NH2)) and composition (Cr/Fe molar ratio: on BSA(-NH2) ≫ HA > SA(-COOH)) of heterogeneous precipitates. Negatively charged -COOH attracted more Fe ions and oligomers of hydrolyzed Fe/Cr species and subsequently promoted heterogeneous precipitation of Fe/Cr hydroxide nanoparticles. Organic coatings containing -NH2 were positively charged at acidic pH because of the high pKa value of the functional group, limiting cation adsorption and formation of coprecipitates. Meanwhile, the higher local pH near the -NH2 coatings promoted the formation of Cr(OH)3. This study advances fundamental understanding of heterogeneous Fe/Cr hydroxide coprecipitation on organics, which is essential for successful Cr remediation and removal in both natural and engineered settings, as well as the synthesis of Cr-doped iron (oxy)hydroxides for material applications.

Novel self-expandable stent-based endobiliary radiofrequency ablation for unresectable malignant biliary obstruction.

BACKGROUND AND AIMS: Endobiliary radiofrequency ablation (RFA) is an emerging endoscopic palliative adjunctive therapy used for the local treatment of unresectable malignant biliary obstruction (MBO). However, irregular ablation ranges caused by insufficient electrode-to-bile duct contact pose a significant obstacle. We investigated the feasibility of a self-expandable stent (SES)-based electrode with a customized RFA generator in the porcine liver and common bile duct (CBD). METHODS: An SES-RFA system with polarity switching was developed to perform endobiliary RFA. The ablation ranges of 20 ablation protocols were evaluated to validate the feasibility of the newly developed RFA system in the porcine liver. Nine of 20 ablation protocols were selected for evaluation in the porcine CBD with cholangiography, endoscopy, and histologic and immunohistochemical analysis. RESULTS: The SES-RFA system with polarity switching was successfully constructed and demonstrated high accuracy and reproducibility. The ablation area was clearly identified between the 2 SESs. The ablation ranges and degree of mucosal damage, including terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling-positive and heat shock protein 70-positive depositions, increased proportionally with ablation protocols in the porcine liver and CBD (all P < .05). Ablation length and depth linearly increased with ablation protocols from 8.74 ± .25 to 31.25 ± .67 mm and 1.61 ± .09 to 11.94 ± .44 mm, respectively. CONCLUSIONS: The SES-RFA system with polarity switching between electrodes provided an even circumferential area of ablation and enhanced ablation depth between the electrodes. This novel endobiliary RFA system is a promising modality for local ablation in patients with unresectable MBO.