Blocking Mechanism Research Articles

Knee Osteoarthritis Treated by Ultrasound-guided Genicular Nerve Block Combined with IPACK Block: Case Report

Background: The prevalence rate of knee osteoarthritis (KOA) in China ranks first among all types of OA. A nerve block is a crucial intervention method for treating the pain of KOA patients in the early and middle stages. This paper aims to analyze the mechanism of ultrasound-guided genicular nerve block (GNB) combined with infiltration between the popliteal artery and capsule of the knee (IPACK) block in treating KOA pain by reporting the diagnosis and treatment of a KOA patient. Case Report: The patient, a 71-year-old woman, complained of “intermittent knee joint pain for several years, aggravated and with limited mobility for one month” and was treated in the outpatient department of the Yanbian University Hospital. After a physical and auxiliary examination, it was diagnosed as bilateral KOA, Kellgren-Lawrence level II, and GNB combined with IPACK block was proposed. Conclusion: GNB can achieve analgesia in front of the knee joint, eliminate aseptic inflammation and edema of patella medial plica (PMP), and assist with postoperative rehabilitation exercise, which is conducive to early improvement of lower limb function. IPACK block has a good analgesic effect behind the knee joint. The combination of GNB and IPACK block may play an essential role in future KOA pain treatment. Key words: Case report, genicular nerve block, IPACK block, knee, osteoarthritis, ultrasound-guided

From General Circulation to Global Change: The Evolution, Achievements, and Influences of Duzheng Ye’s Scientific Research

Duzheng Ye (Tu-cheng Yeh) was an active member of Rossby’s Chicago School, one of the founders of modern meteorology in China since the 1950s, and a pioneer of global change science in China and over the world. His achievements have been central to the development of atmospheric and climate dynamics and global change studies in China, and many of them remain to be fundamental in the context of global climate change. In this review, his lifelong research career is divided into five periods: (1) the preparatory period (1935–1944); (2) the Chicago period (1945–1950); (3) the period of breaking ground (1950–1966); (4) the period of transition (1972–1983); and (5) the period of global change (1984–2013). The evolution of Yeh’s main achievements is described in the context of the historical background of both China and the world. These well-known achievements included the theory of energy dispersion in the atmosphere, the general circulation of the atmosphere (GCA) over East Asia and the globe, Qinghai–Tibetan Plateau meteorology, the scale-dependence theory of geostrophic adaptation (adjustment), and his pioneering ideas on global change. Special emphases are put on some of Yeh’s investigations that were well ahead of his time, such as his investigations on trade inversion, the GCA as an internally consistent whole, abrupt seasonal changes in the GCA, the physical mechanism of atmospheric blocking, and orderly human activities.

PHCU-Net: A parallel hierarchical cascade U-Net for skin lesion segmentation

Melanoma is a malignant tumor condition which can be successfully cured with early detection and treatment. Currently, deep learning is one of the research hotspots in automatic diagnosis, with two primary categories of medical image segmentation applications: Convolution Neural Network (CNN) methods such as U-Net and Transformer-based methods. Despite achieving remarkable performance in image segmentation, both above approaches have some inherent shortcomings that cannot be overlooked. The convolution operation in the CNN structure cannot adequately capture global dependencies, leading to a major negative impact on segmentation performance. While the Multi-head Self-Attention mechanism in Transformer can efficiently extract extensive global features, its large computational complexity and lack of local induction bias cannot be ignored. These factors result in a significant reduction in the precision of clinical diagnosis using automated segmentation. To address the aforementioned issues, this paper proposes a U-shaped network structure called PHCU-Net which comprises global feature block, local feature block and dual-branch hierarchical attention mechanism that is designed specifically for the segmentation network of skin lesions. In addition, we argue that the traditional skip connection can be further improved to acquire stronger contexts by simply incorporating convolution attention, so that the decoder can fully collect the global and local feature information. The aforementioned innovative work empowers our model to generate superior skin lesion segmentation results compared to other classical algorithms and deep learning-based models. Extensive experimental results on three open-source datasets (ISIC2017, ISIC2018, and PH2) demonstrate the effectiveness of the proposed PHCU-Net in melanoma lesion segmentation.

The structural basis of divalent cation block in a tetrameric prokaryotic sodium channel

Divalent cation block is observed in various tetrameric ion channels. For blocking, a divalent cation is thought to bind in the ion pathway of the channel, but such block has not yet been directly observed. So, the behaviour of these blocking divalent cations remains still uncertain. Here, we elucidated the mechanism of the divalent cation block by reproducing the blocking effect into NavAb, a well-studied tetrameric sodium channel. Our crystal structures of NavAb mutants show that the mutations increasing the hydrophilicity of the inner vestibule of the pore domain enable a divalent cation to stack on the ion pathway. Furthermore, non-equilibrium molecular dynamics simulation showed that the stacking calcium ion repel sodium ion at the bottom of the selectivity filter. These results suggest the primary process of the divalent cation block mechanism in tetrameric cation channels.

Synthesis of Backbone-Modified Morpholino Oligonucleotides Using Phosphoramidite Chemistry.

Phosphorodiamidate morpholinos (PMOs) are known as premier gene knockdown tools in developmental biology. PMOs are usually 25 nucleo-base-long morpholino subunits with a neutral phosphorodiamidate linkage. PMOs work via a steric blocking mechanism and are stable towards nucleases' inside cells. PMOs are usually synthesized using phosphoramidate P(V) chemistry. In this review, we will discuss the synthesis of PMOs, phosphoroamidate morpholinos (MO), and thiophosphoramidate morpholinos (TMO).

Cryo-EM structures of ClC-2 chloride channel reveal the blocking mechanism of its specific inhibitor AK-42

ClC-2 transports chloride ions across plasma membranes and plays critical roles in cellular homeostasis. Its dysfunction is involved in diseases including leukodystrophy and primary aldosteronism. AK-42 was recently reported as a specific inhibitor of ClC-2. However, experimental structures are still missing to decipher its inhibition mechanism. Here, we present cryo-EM structures of apo ClC-2 and its complex with AK-42, both at 3.5 Å resolution. Residues S162, E205 and Y553 are involved in chloride binding and contribute to the ion selectivity. The side-chain of the gating glutamate E205 occupies the putative central chloride-binding site, indicating that our structure represents a closed state. Structural analysis, molecular dynamics and electrophysiological recordings identify key residues to interact with AK-42. Several AK-42 interacting residues are present in ClC-2 but not in other ClCs, providing a possible explanation for AK-42 specificity. Taken together, our results experimentally reveal the potential inhibition mechanism of ClC-2 inhibitor AK-42.

Qualitative ultrasound biomicroscopy in glaucoma.

UBM is a high-resolution ultrasound technique which allows non-invasive, in vivo imaging of the anterior segment and iridocorneal angle. This video is compilation of short video clips and images which gives description on identification of angle closure due to pupillary block, peripheral anterior synechiae, iris bombe, plateau iris, supra ciliary effusion, and malignant glaucoma. It also shows video demonstrating partially and fully patent iridotomy and features of trabeculectomy bleb. Synopsis: This video summarizes importance of UBM application in angle closure glaucoma to understand its pathophysiology by showing the relationship between the peripheral iris, trabecular meshwork and ciliary processes. UBM provides two-dimensional, grayscale images of the angle structures and allows identification of non-pupillary block mechanism in angle closure glaucoma, which can be recorded for qualitative and quantitative analyses. https://youtu.be/prsmGnR8jYc.

Tidal Effect on Grouting and Blocking of Flowing Water in Karst Fractures: Numerical Implementation and Its Application

The issue of water blocking by grouting in coastal areas has engendered the need for a novel numerical simulation method for grouting with a flowing water under tidal action, two-fluid tracking (TFT). This paper proposes such a method. First, based on the material derivative, the transport model of the residence time of injected slurry was derived. In addition, the residence time of injected slurry microgroups at any grouting time was obtained by solving the transport model. Further, the numerical characterization of slurry viscosity during grouting in flowing water was realized by introducing a time-varying viscosity function obtained from previous experiments. Then, based on the generalized tidal action model, the diffusion behavior and blocking mechanism of slurry under tidal effects were studied. The results show that: (1) under tidal action, the water velocity fluctuates and decreases, whereas the grouting pressure fluctuates and increases; (2) at the early stage of grouting, the diffusion pattern of slurry appears as a droplet, and the tailing phenomenon becomes more serious with an increase of tidal intensity; with the progress of grouting, the diffusion pattern gradually changes to U-shaped or elliptical; (3) the strong tidal action will reduce the retention rate of slurry, which is not conducive to the grouting blocking. The research results have been applied to the grouting treatment of a China Resources Cement (Hepu) limestone mine. This research can provide some useful guidance for grouting treatment engineering of water inflow in coastal areas.

Effect of PD-1 Inhibitor on PI3K/AKT Pathway in Tumor Cell and TCell Activity in Non-small Cell lung Cancer (NSCLC)

Lung cancer is one of the most lethal cancers around the world and non-small cell lung cancer takes up about 85% ofthe cases. PD-1 inhibitor is an antibody used in immunotherapy to treat cancer. Previous studies have reported thatthe PD-1 inhibitor can block the PD-1/PD-L1 binding and help the immune system recognize and attack tumors. ThePI3K/AKT signaling pathway is an important target of the PD-1 downstream pathway. This paper studies the effects ofPD-1 inhibitor Pembrolizumab on the activation of the PI3K/AKT pathway in vivo. In this study, A549 cell line willbe used as the non-small cell lung cancer model. The immune-deficient mice will be injected with Keytruda, saline(negative control) or Taxol (positive control). Flow cytometry and Western Blot will be used to measure the activationof tumor cells and CD4 T cells. This paper investigates whether or not PD-1 inhibitor would effectively block thePI3K/AKT pathway and increase T cell proliferation. The result of this study will explore the blocking mechanism ofPembrolizumab on PI3K/AKT pathway. Future studies should focus on the acquired resistance caused by mutations andits effects on PD-1 inhibitor treatment with PI3K/AKT pathway activation as the biomarker.

Magnetic mining waste based-membranes for trimethoprim removal and fouling mitigation with ozone

The use of ceramic membranes for microfiltration have increased due to their high performance and physical–chemical properties, but their production is still very expensive. For this reason, geopolymeric membranes (GPMs) have been developed with similar characteristics and reduced fabrication costs by incorporating industrial waste. In this study, GPMs were synthesized by incorporating different amounts of magnetic mining waste (MMW), characterized, and used to remove trimethoprim antibiotic from an aqueous solution. Moreover, the presence of high iron oxide content in the membrane composition, ozone could be used as the cleaning agent due to the in situ generation of reactive oxygen species. The porosity of the membranes was widely investigated with micro-CT. MMW incorporation was found to be highly beneficial for increasing the percentage of open pores’ and narrowing the distribution of pore size. The addition of a porogenic agent (H2O2) did not have the expected effects, since a significant number of both closed and very large pores (400–800 µm) were formed. The geopolymeric membranes produced by MMW incorporation up to 50% (w/w) exhibited high hydraulic permeability (6.4–7.0 L·m−2·h−1·bar−1), mechanical strength (30–38 MPa) and open porosity. Yet, rejection rates doubled with the incorporation of 50% (w/w) MMW, despite its high flux decay. Nevertheless, the flux was easily recovered by the reactions between foulant compounds and ozone, which was used as cleaning agent. The filtration performance was evaluated to remove trimethoprim dissolved in aqueous solution and the flux decay was successfully described according to the Hermia’s law, and a complete pore blocking mechanism was used. It is possible that trimethoprim molecules interact between them or with buffer reactants, forming complexes, which can be removed by ozone reactions.

EBF1-JAK2 inhibits the PAX5 function through physical interaction with PAX5 and kinase activity.

Gene aberrations of B-cell regulators and growth signal components such as the JAK-STAT pathway are frequently found in B-cell acute lymphoblastic leukemia (B-ALL). EBF1 is a B-cell regulator that regulates the expression of PAX5 and co-operates with PAX5 to regulate B-cell differentiation. Here, we analyzed the function of the fusion protein of EBF1 and JAK2, EBF1-JAK2 (E-J). E-J caused constitutive activation of JAK-STAT and MAPK pathways and induced autonomous cell growth in a cytokine-dependent cell line. E-J did not affect the transcriptional activity of EBF1 but inhibited that of PAX5. Both the physical interaction of E-J with PAX5 and kinase activity of E-J were required for E-J to inhibit PAX5 function, although the detailed mechanism of inhibition remains unclear. Importantly, gene set enrichment analysis using the results of our previous RNA-seq data of 323 primary BCR-ABL1-negative ALL samples demonstrated repression of the transcriptional target genes of PAX5 in E-J-positive ALL cells, which suggests that E-J also inhibited PAX5 function in ALL cells. Our results shed new light on the mechanisms of differentiation block by kinase fusion proteins.

Bi-allelic variants in ASTL cause abnormal fertilization or oocyte maturation defects.

Fertilization is a fundamental process of development, and the blocking mechanisms act at the zona pellucida (ZP) and plasma membrane of the egg to prevent any additional sperm from binding, permeating and fusing after fertilization. In clinical practice, some couples undergoing recurrent IVF failures that mature oocytes had abnormal fertilization for unknown reason. Ovastacin encoded by ASTL cleave the ZP protein ZP2 and play a key role in preventing polyspermy. Here, we identified bi-allelic variants in ASTL that are mainly characterized by fertilization problems in humans. All four independent affected individuals had bi-allelic frameshift variants or predicted damaging missense variants, which follow a Mendelian recessive inheritance pattern. The frameshift variants significantly decreased the quantity of ASTL protein in vitro. And all missense variants affected the enzymatic activity that cleaves ZP2 in mouse egg in vitro. Three knock-in female mice (corresponding to three missense variants in patients) all show subfertility due to low embryo developmental potential. This work presents strong evidence that pathogenic variants in ASTL cause female infertility and provides a new genetic marker for the diagnosis of fertilization problems.

穴盘苗基质块仿真粘结参数标定与试验

To accurately simulate the interactions between the plug seedlings and the planter during the planting process and explore the damage mechanism of the plug seedling substrate block, the bonding parameters of plug seedlings substrate block were calibrated by the discrete element method. The physical puncture test showed that the average of maximum force of the cone indenter on substrate block measured by texture analyzer was 4.633 N. A Hertz-Mindlin with the bonding model was established for the substrate block in EDEM software. A virtual calibration experiment was designed with the puncture force of substrate block as the evaluation index. The two-level factorial test and the steepest climbing test were used to screen out the significant parameters and the optimal interval. Then, the Box-Behnken test and the optimization solution were used to obtain the optimal bonding parameter combination of the substrate block particles. Finally, the optimal parameter combination was simulated and verified. The relative error of the maximum puncture force between the simulated value and the measured value was 1.88 %, which indicated that the bonding parameters of the substrate block obtained by calibration were accurate and reliable.

Design of a Phase 1, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-Ascending Doses of PGN-EDODM1 in Adult Participants with Myotonic Dystrophy Type 1 (DM1) (P6-8.004)

<h3>Objective:</h3> The primary objective of this single-ascending dose (SAD) study is to evaluate the safety and tolerability of PGN-EDODM1 in adults living with DM1. Secondary and exploratory objectives include pharmacokinetics (PK), muscle distribution, pharmacodynamics (changes in splicing pattern of transcripts), and select functional outcome measures. <h3>Background:</h3> PepGen’s Enhanced Delivery Oligonucleotide (EDO) cell-penetrating peptide technology is engineered to optimize tissue delivery and cellular uptake of therapeutic oligonucleotides. PGN-EDODM1 is being evaluated for the treatment of DM1. PGN-EDODM1 binds to the pathogenic CUG repeat expansion in <i>DMPK</i> mRNA and reduces sequestration of Muscleblind (MBNL) proteins through a steric blocking mechanism. Release of MBNL proteins is hypothesized to correct DM1 spliceopathy; the root cause of DM1. <h3>Design/Methods:</h3> Males and females 18–50 years of age, inclusive, with genetically confirmed diagnosis of DM1 will be eligible to participate, and will be randomized 3:1 (6 active, 2 placebo) to receive PGN-EDODM1 or placebo in each dose cohort. A muscle needle biopsy (tibialis anterior) will be performed at baseline and at Weeks 4 and 16 post-dosing for measurement of splicing of selected transcripts. An independent data safety and monitoring committee will oversee dose escalation. <h3>Results:</h3> The doses to be assessed will be based on data from the preclinical data and data from the Phase 1 healthy volunteer safety study of our lead EDO, PGN-EDO51. A plan for analysis of safety measures such as vital signs, electrocardiograms, clinical chemistry, urinalysis, and biomarkers will be presented, along with details on proposed functional endpoints and biomarkers to be explored in this study. <h3>Conclusions:</h3> This Phase 1 SAD clinical study will support continued development of PGN-EDODM1 for the treatment of DM1, and will be initiated in 2023. Participants will be invited to enroll in a planned multiple-ascending dose study (MAD) and a subsequent open-label extension study. <b>Disclosure:</b> Dr. Mellion has received personal compensation for serving as an employee of PepGen. Dr. Mellion has stock in PepGen. Dr. Larkindale has received personal compensation for serving as an employee of PepGen. Jennifer Cormier has nothing to disclose. Ms. Hand has received personal compensation for serving as an employee of 4D Molecular Therapeutics. Ms. Hand has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Fulcrum Therapeutics, Inc.. Ms. Hand has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for PepGen Inc. Ms. Hand has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Bluebird Bio. Ms. Vacca has received personal compensation for serving as an employee of PepGen Inc. Ms. Vacca has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for PepGen Inc. Ms. Vacca has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Agios Pharmaceuticals. Ms. Vacca has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Nocion Therapeutics. Ms. Vacca has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Relmada Therapeutics. Ms. Vacca has stock in PepGen Inc.. Pallavi Lonkar has nothing to disclose. Dr. Holland has received personal compensation for serving as an employee of PepGen Inc.. Dr. Holland has received intellectual property interests from a discovery or technology relating to health care. Mr. Garg has received personal compensation for serving as an employee of PepGen. Mr. Garg has stock in pepgen. Mr. Foy has received personal compensation for serving as an employee of PepGen Inc.. Dr. McArthur has received personal compensation for serving as an employee of PepGen . Dr. McArthur has stock in PepGen .

PGN-EDODM1: Preclinical Data Supporting the Development of an Enhanced Delivery Oligonucleotide (EDO) for the Treatment of Myotonic Dystrophy Type 1 (DM1) (S48.001)

<h3>Objective:</h3> In vitro and in vivo evaluation of pharmacological activity via measurement of splicing changes, nuclear RNA foci, and myotonia. <h3>Background:</h3> PepGen’s EDO cell-penetrating peptide technology is engineered to optimize tissue delivery and cellular uptake of therapeutic oligonucleotides. PGN-EDODM1 is being evaluated for the treatment of DM1. PGN-EDODM1 binds to the pathogenic CUG repeat expansion in <i>DMPK</i> mRNA and reduces sequestration of Muscleblind (MBNL) proteins within nuclear RNA foci through a steric blocking mechanism. Release of MBNL proteins is hypothesized to correct DM1 spliceopathy; a central cause of DM1. <h3>Design/Methods:</h3> DM1 donor cells with 2,600 CTG repeats were treated with PGN-EDODM1 (1, 2, 5, 10, or 20 μM). Nuclear RNA foci profiles and splicing events were evaluated after 24 hours. PGN-EDODM1 (0, 10, 20, 30, and 50 mg/kg) was administered intravenously (IV) to wildtype (WT) or HSA^LR mice (DM1 murine model containing 250 CTG repeats in the <i>HSA</i> gene). Splicing profiles were evaluated in gastrocnemius and quadricep muscles 2-weeks post dose and myotonia was quantitatively assessed. Tissue levels of PGN-EDODM1 were analyzed. To explore the duration of pharmacological activity, PGN-EDODM1 (30 mg/kg IV) was administered to WT and HSA^LR mice and splicing profiles were evaluated 12 or 24 weeks post-dose. <h3>Results:</h3> The cellular model showed dose-dependent reduction in toxic RNA foci and correction of mis-splicing. In the HSA^LR model, a single dose resulted in high muscle concentrations of PGN-EDODM1, dose-dependent correction of mis-splicing (persisting over 24 weeks), and resolution of myotonia. PGN-EDODM1 was generally well tolerated at pharmacological doses. <h3>Conclusions:</h3> These preclinical studies demonstrate that PGN-EDODM1 reduced nuclear RNA foci and corrected mis-splicing at clinically relevant, tolerable doses with effects lasting up to 24 weeks. The HSA^LR mouse showed resolution of myotonia after a single PGN-EDODM1 dose. A Phase 1 clinical study in adults with DM1 will be initiated in 2023. <b>Disclosure:</b> Dr. Holland has received personal compensation for serving as an employee of PepGen Inc.. Dr. Holland has received intellectual property interests from a discovery or technology relating to health care. Mr. Klein has nothing to disclose. Caroline Godfrey has nothing to disclose. Dr. Svenstrup has received personal compensation for serving as an employee of PepGen, Inc. Dr. Svenstrup has stock in PepGen, Inc. Dr. Larkindale has received personal compensation for serving as an employee of PepGen. Dr. Bracegirdle has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for PepGen Inc. Dr. Furling has nothing to disclose. Dr. Goyal has received personal compensation for serving as an employee of Pepgen Inc.. Dr. Goyal has received personal compensation for serving as an employee of Wave Life Sciences. Dr. Goyal has received personal compensation in the range of $100,000-$499,999 for serving as an officer or member of the Board of Directors for Pepgen Inc.. Dr. Goyal has stock in PepGen Inc..

Infection routes, invasion mechanisms, and drug inhibition pathways of human coronaviruses on the nervous system.

So far, numerous studies have reported on how coronaviruses affect the human nervous system. However, these studies mainly focused on the impact of a single coronavirus on the nervous system, and failed to fully report the invasion mechanisms and the rules of symptoms of the seven human coronaviruses. This research can assist medical professionals in identifying the regularity of coronavirus invasion into the nervous system by examining the impacts of human coronaviruses on the nervous system. Meanwhile, the discovery also helps humans to prevent the damage to the human nervous system caused by the more novel coronavirus in advance, thus reducing the rate of disease transmission and fatality caused by such viruses. In addition to describing the structures, routes of infection, and symptomatic manifestations of human coronaviruses, this review also finds that the structures of human coronaviruses correlate with virulence, pathways of infection, and blocking mechanisms of drugs. This review can provide a theoretical basis for the research and development of related drugs, promote the prevention and treatment of coronavirus infectious diseases, and contribute to global epidemic prevention.

Synergistic inhibition of thermal runaway propagation of lithium-ion batteries by porous materials and water mist

The thermal runaway (TR) propagation of lithium-ion batteries (LIBs) is characterized by fast spread and violent reaction, which can cause a massive fire and even explosion. Blocking TR propagation of LIBs and cooling batteries are crucial to avoid the exacerbation of hazards. In this study, three porous materials (nickel foam, glass wool and nanoporous aerogel) were selected as barriers for LIBs and the corresponding blocking mechanism on TR propagation of LIBs were investigated. Based on this, water mist is released at the moment of thermal runaway of the lithium-ion battery and used to cool the battery. In this work, further research on the inhibition of thermal runaway and its propagation in lithium-ion batteries by porous materials and water mist is carried out. The results show that a good suppression effect can be obtained by a synergistic mechanism of pre-insulation and subsequent heat dissipation with the synergistic action of porous materials and water mist. This study also used the failure mode effects analysis (FMEA) method to evaluate the reliability of the inhibition methods and reveal the application effect of FMEA in the field of LIBs.

A NIR‐II Fluorescent Probe for Hydrogen Sulfide Detection Based on Blocking Intramolecular Charge Transfer

AbstractA NIR‐II fluorescent probe (Et‐1080) for H2S detection was fabricated based on the intramolecular charge transfer blocking mechanism. The enhanced electron density of the indole donor further drove the Et‐1080′s absorption and emission to the NIR‐II region with a high molar absorption coefficient and acceptable fluorescence quantum yield. The C=N double bond of electron‐deficient indole can react with H2S rapidly via a nucleophilic addition mechanism, resulting in the destruction of conjugated structure and fluorescence quenching of the Et‐1080 molecule. The probe showed high selectivity and sensitivity to H2S, which could realize the rapid detection of H2S in NIR‐II band and showed great potential in the further disease diagnosis associated with H2S.

Molecular determinants of μ-conotoxin KIIIA interaction with the human voltage-gated sodium channel NaV1.7.

The voltage-gated sodium (NaV) channel subtype NaV1.7 plays a critical role in pain signaling, making it an important drug target. Here we studied the molecular interactions between μ-Conotoxin KIIIA (KIIIA) and the human NaV1.7 channel (hNaV1.7). We developed a structural model of hNaV1.7 using Rosetta computational modeling and performed in silico docking of KIIIA using RosettaDock to predict residues forming specific pairwise contacts between KIIIA and hNaV1.7. We experimentally validated these contacts using mutant cycle analysis. Comparison between our KIIIA-hNaV1.7 model and the cryo-EM structure of KIIIA-hNaV1.2 revealed key similarities and differences between NaV channel subtypes with potential implications for the molecular mechanism of toxin block. The accuracy of our integrative approach, combining structural data with computational modeling, experimental validation, and molecular dynamics simulations, suggests that Rosetta structural predictions will be useful for rational design of novel biologics targeting specific NaV channels.

Deep-learning-based ring artifact correction for tomographic reconstruction.

X-ray tomography has been widely used in various research fields thanks to its capability of observing 3D structures with high resolution non-destructively. However, due to the nonlinearity and inconsistency of detector pixels, ring artifacts usually appear in tomographic reconstruction, which may compromise image quality and cause nonuniform bias. This study proposes a new ring artifact correction method based on the residual neural network (ResNet) for X-ray tomography. The artifact correction network uses complementary information of each wavelet coefficient and a residual mechanism of the residual block to obtain high-precision artifacts through low operation costs. In addition, a regularization term is used to accurately extract stripe artifacts in sinograms, so that the network can better preserve image details while accurately separating artifacts. When applied to simulation and experimental data, the proposed method shows a good suppression of ring artifacts. To solve the problem of insufficient training data, ResNet is trained through the transfer learning strategy, which brings advantages of robustness, versatility and low computing cost.