One-dimensional magnetic chains for methylene blue removal.

Adsorption is a promising method for the treatment of wastewater from the dyestuff industry due to its simplicity, high efficiency, low energy consumption and no secondary pollution. The capacity to separate adsorbents in a timely and efficient manner is a crucial factor in industrial applications. One-dimensional magnetic chains modified with polydopamine and in situ generated Ag nanoparticles (MC@PDA-Ag) were fabricated as highly regenerable adsorbents for methylene blue (MB). The magnetic chains were characterized by scanning electron microscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy, nitrogen adsorption/desorption, X-ray photoelectron spectrometry, X-ray diffraction and magnetometry. The adsorption and catalytic degradation of MB by the materials were investigated. The regeneration capacity of MC@PDA-Ag was also evaluated. The specific saturation magnetization of MC@PDA-Ag is 38.2 emu g-1. The adsorption capacity of MC@PDA-Ag remained 76% of the initial value after 12 cycles of adsorption and elution. The novel adsorbents, which integrate adsorption and catalytic degradation, are anticipated to facilitate the development of magnetic adsorption materials for the remediation of dye pollution.

Constructing soybean protein isolate /bacterial cellulose co-assemblies by pH shifting treatment: Molecular conformation and physicochemical properties.

The study elucidates that the pH shifting treatment unfolds the conformation of soybean protein isolate (SPI), enabling it to intertwine with bacterial cellulose (BC) and form SPI/BC co-assemblies. Results from intrinsic fluorescence spectroscopy and surface hydrophobicity indicate that the SPI with pH shifting treatment shows a notable blue shift in maximum emission wavelength and increased surface hydrophobicity. It demonstrates that pH shifting treatment facilitates the unfolding of SPI's molecular conformation, promoting its entanglement with high aspect ratio BC. Particle size distribution and microstructural analysis further demonstrate that the pH shifting treatment facilitates the formation of SPI/BC co-assemblies. Evaluation of processing properties reveals that the SPI/BC co-assemblies exhibited exceptional gel and emulsification properties, with gel strength and emulsifying activity respectively six and two times higher than natural SPI. This enhancement is attributed to the thickening properties of BC with a high aspect ratio and the superior hydrophobicity of SPI in its molten globule state.

A gas spark switch electrode impact pressure test platform.

The discharge arc of a high-current gas spark switch has a strong mechanical effect on the electrode and adjacent objects. The measurement of this mechanical effect on the electrode plays a very important role in switch design and the theoretical study of spark discharge. However, in traditional stress measurement systems, the spatial electromagnetic interference caused by the discharge and the high electrode voltage affects the measurement accuracy and can even damage the experimental instrument. In this paper, an electrode impact stress measurement system based on PVDF piezoelectric film is designed to measure the electrode stress under a strong spatial electromagnetic field and high voltage. The experimental results show that the system can measure the impact pressure of high-voltage and high-current gas spark switch electrodes. The starting time of the stress measurement waveform shows that the shock to the electrode is formed in the initial stage of current buildup. The measured results clearly show the high magnetic field force component in the electrode impact pressure waveform. The shock waveforms induced by different pulse capacitor values, breakdown voltages, and loads are examined. It is found that the shock stress waveforms applied to the electrodes are affected by the peak value of the current, dI/dt, and the discharge duration.

J-shaped associations of pan-immune-inflammation value and systemic inflammation response index with stroke among American adults with hypertension: evidence from NHANES 1999-2020.

Introduction: Stroke, a leading cause of death and disability worldwide, is primarily ischemic and linked to hypertension. Hypertension, characterized by systemic chronic inflammation, significantly increases stroke risk. This study explores the association of novel systemic inflammatory markers (SII, PIV, SIRI) with stroke prevalence in hypertensive U.S. adults using NHANES data. Methods: We analyzed data from hypertensive participants in the NHANES 1999-2020 survey, excluding those under 20, pregnant, or with missing data, resulting in 18,360 subjects. Systemic inflammatory markers (SII, PIV, SIRI) were calculated from blood counts. Hypertension and stroke status were determined by self-report and clinical measurements. Covariates included sociodemographic, lifestyle, and medical history factors. Weighted statistical analyses and multivariate logistic regression models were used to explore associations, with adjustments for various covariates. Ethical approval was obtained from the NCHS Ethics Review Board. Results: In a cohort of 18,360 hypertensive individuals (mean age 56.652 years), 7.25% had a stroke. Stroke patients were older, had lower PIR, and were more likely to be female, single, less educated, smokers, non-drinkers, physically inactive, and have diabetes and CHD. Multivariate logistic regression showed that SII was not significantly associated with stroke. However, PIV and SIRI were positively associated with stroke prevalence. Each unit increase in lnPIV increased stroke odds by 14% (OR = 1.140, p = 0.0022), and lnSIRI by 20.6% (OR = 1.206, p = 0.0144). RCS analyses confirmed J-shaped associations for lnPIV and lnSIRI with stroke. Stratified analyses identified gender and smoking as significant effect modifiers. Smoking was significantly associated with elevated PIV, SIRI, and SII levels, especially in current smokers. Conclusion: Elevated PIV and SIRI levels significantly increase stroke prevalence in hypertensive individuals, notably among males and smokers. A predictive model with PIV, SIRI, and sociodemographic factors offers strong clinical utility.

Second-harmonic generation of 2D materials excited by the Laguerre-Gaussian beam.

We theoretically study the second-harmonic generation (SHG) of two-dimensional (2D) materials excited by a Laguerre-Gaussian (LG) beam at normal incidence and provide a method to distinguish SHG induced by the electric dipole (ED) interaction and SHG induced by the electric quadrupole and magnetic dipole (EQ-MD) interaction by their different dependence on the LG beam parameters, including the effective spot area v02 and the order of orbital angular momentum (OAM) m. In an approximation of neglecting reflection and taking a beam radius to infinity, the intensity of the ED induced SHG is proportional to F m/v02 with Fm = 2-2|m|(2|m|)!/(π(|m|!)2), while the EQ-MD induced one is proportional to (4|m|+2)F m/v04. An in-plane isotropic substrate can strongly affect the signal amplitude but slightly change the v0 and m dependence. Our results provide an all-optical way to detect the OAM by SHG, as well as a theoretical basis for studying the EQ-MD induced SHG by the LG beams.

Fabrication of injectable alginate hydrogels with sustained release of 4-octyl itaconate for articular anti-inflammatory.

BACKGROUND: Osteoarthritis (OA) is a chronic and degenerative joint disease that remains a great challenge in treatment due to the lack of effective therapies. 4-octyl itaconate (4-OI) is a novel and potent modulator of inflammation for the treatment of inflammatory disease. However, the clinical usage of 4-OI is limited due to its poor solubility and low bioavailability. As a promising drug delivery strategy, injectable hydrogels offers an effective approach to address these limitations of 4-OI. OBJECTIVE: The aim of the study was to verify that the composite 4-OI/SA hydrogels could achieve a controlled release of 4-OI and reduce damage to articular cartilage in the group of osteoarthritic rats treated with the system. METHODS: In this study, an injectable composite hydrogel containing sodium alginate (SA) and 4-octyl itaconate (4-OI) has been developed for continuous intra-articular administration in the treatment of OA. RESULTS: After intra-articular injection in arthritic rats, the as-prepared 4-OI/SA hydrogel containing of 62.5 µM 4-OI effectively significantly reduced the expression of TNF-α, IL-1ß, IL-6 and MMP3 in the ankle fluid. Most importantly, the as-prepared 4-OI/SA hydrogel system restored the morphological parameters of the ankle joints close to normal. CONCLUSION: 4-OI/SA hydrogel shows a good anti-inflammatory activity and reverse cartilage disruption, which provide a new strategy for the clinical treatment of OA.

Dual-site molecular glues for enhancing protein-protein interactions of the CDK12-DDB1 complex.

Protein-protein interactions (PPIs) stabilization with molecular glues plays a crucial role in drug discovery, albeit with significant challenges. In this study, we propose a dual-site approach, targeting the PPI region and its dynamic surroundings. We conduct molecular dynamics simulations to identify critical sites on the PPI that stabilize the cyclin-dependent kinase 12 - DNA damage-binding protein 1 (CDK12-DDB1) complex, resulting in further cyclin K degradation. This exploration leads to the creation of LL-K12-18, a dual-site molecular glue, which enhances the glue properties to augment degradation kinetics and efficiency. Notably, LL-K12-18 demonstrates strong inhibition of gene transcription and anti-proliferative effects in tumor cells, showing significant potency improvements in MDA-MB-231 (88-fold) and MDA-MB-468 cells (307-fold) when compared to its precursor compound SR-4835. These findings underscore the potential of dual-site approaches in disrupting CDK12 function and offer a structural insight-based framework for the design of cyclin K molecular glues.

The causality of atrial fibrillation on frailty index: A Mendelian randomization study.

Prior epidemiological research has indicated a possible association between atrial fibrillation (AF) and frailty status. Our study used Mendelian randomization to estimate its causality. The genome-wide association studies for AF were utilized as the exposure for individuals included in the UK Biobank (n = 463,010) and publicly available summary statistics data sets of genome-wide association studies meta-analyses for frailty index in individuals of European descent (n = 175,226) was used as the outcome. The inverse variance weighting method was utilized to evaluate causality. To further confirm the reliability of the results, sensitivity analyses were conducted. The inverse variance weighting analysis indicated that the presence of AF was found to be statistically linked to an increased risk of frailty (odds ratio = 3.017, CI: 1.106-8.232, P = .031). MR-Egger intercept test indicated no pleiotropy (Egger intercept = .002, P = .808). The leave-one-out method indicated that the individual SNPs did not have an impact on the robustness of the findings. The research implies a causal relationship between AF and frailty. Early detection and timely intervention of AF can control the occurrence of frailty.

Small Molecule Targeting PPM1A Activates Autophagy for Mycobacterium tuberculosis Host-Directed Therapy.

Mycobacterium tuberculosis (Mtb), the infectious agent of tuberculosis (TB), causes over 1.5 million deaths globally every year. Host-directed therapies (HDT) for TB are desirable for their potential to shorten treatment and reduce the development of antibiotic resistance. Previously, we described a modular biomimetic strategy to identify SMIP-30, targeting PPM1A (IC50 = 1.19 µM), a metal-dependent phosphatase exploited by Mtb to survive intracellularly. SMIP-30 restricted the survival of Mtb in macrophages and lungs of infected mice. Herein, we redesigned SMIP-30 to create SMIP-031, which is a more potent inhibitor for PPM1A (IC50 = 180 nM). SMIP-031 efficiently increased the level of phosphorylation of S403-p62 and the expression of LC3B-II to activate autophagy, resulting in the dose-dependent clearance of Mtb in infected macrophages. SMIP-031 possesses a good pharmacokinetic profile and oral bioavailability (F = 74%). In vivo, SMIP-031 is well tolerated up to 50 mg/kg and significantly reduces the bacteria burden in the spleens of infected mice.

Structure-Based Design and Discovery of a Potent and Cell-Active LC3A/B Covalent Inhibitor.

Autophagy is a highly conserved cellular homeostasis maintenance mechanism in eukaryotes. Microtubule-associated protein light chain 3 (LC3) plays a crucial role in autophagy. It has multiple pairs of protein-protein interactions (PPIs) with other proteins, and these PPIs have an effect on the regulation of autophagosome formation and the recruitment of autophagic substrates. In our previous work, a small molecule covalent inhibitor DC-LC3in-D5 which could inhibit LC3A/B PPIs was identified, but a detailed study of structure-activity relationships (SARs) was lacking. Herein, a new molecule LC3in-C42 was discovered utilizing the hybridization of advantageous fragments, whose potency (IC50 = 7.6 nM) had been greatly improved compared with that of DC-LC3in-D5. LC3in-C42 inhibits autophagy at the cellular level and its efficacy far exceeds that of DC-LC3in-D5. Thus far, LC3in-C42 stands as the most potent LC3A/B small molecule inhibitor. LC3in-C42 could serve as a powerful tool for LC3A/B protein and autophagy research.

Neurostructural subgroup in 4291 individuals with schizophrenia identified using the subtype and stage inference algorithm.

Machine learning can be used to define subtypes of psychiatric conditions based on shared biological foundations of mental disorders. Here we analyzed cross-sectional brain images from 4,222 individuals with schizophrenia and 7038 healthy subjects pooled across 41 international cohorts from the ENIGMA, non-ENIGMA cohorts and public datasets. Using the Subtype and Stage Inference (SuStaIn) algorithm, we identify two distinct neurostructural subgroups by mapping the spatial and temporal 'trajectory' of gray matter change in schizophrenia. Subgroup 1 was characterized by an early cortical-predominant loss with enlarged striatum, whereas subgroup 2 displayed an early subcortical-predominant loss in the hippocampus, striatum and other subcortical regions. We confirmed the reproducibility of the two neurostructural subtypes across various sample sites, including Europe, North America and East Asia. This imaging-based taxonomy holds the potential to identify individuals with shared neurobiological attributes, thereby suggesting the viability of redefining existing disorder constructs based on biological factors.

The impact of Astragaloside IV on the inflammatory response and gut microbiota in cases of acute lung injury is examined through the utilization of the PI3K/AKT/mTOR pathway.

OBJECTIVES: Astragaloside IV (AS-IV) is a natural triterpenoid saponin compound with a variety of pharmacological effects, and several studies have clarified its anti-inflammatory effects, which may make it an effective alternative treatment against inflammation. In the study, we aimed to investigate whether AS-IV could attenuate the inflammatory response to acute lung injury and its mechanisms. METHODS: Different doses of AS-IV (20mg·kg-1, 40mg·kg-1, and 80mg·kg-1) were administered to the ALI rat model, followed by collection of serum and broncho alveolar lavage fluid (BALF) for examination of the inflammatory response, and HE staining of the lung and colon tissues, and interpretation of the potential molecular mechanisms by quantitative real-time PCR (qRT-PCR), Western blotting (WB). In addition, fecal samples from ALI rats were collected and analyzed by 16S rRNA sequencing. RESULTS: AS-IV decreased the levels of TNF-α, IL-6, and IL-1ß in serum and BALF of mice with Acute lung injury (ALI). Lung and colon histopathology confirmed that AS-IV alleviated inflammatory infiltration, tissue edema, and structural changes. qRT-PCR and WB showed that AS-IV mainly improved inflammation by inhibiting the expression of PI3K, AKT and mTOR mRNA, and improved the disorder of intestinal microflora by increasing the number of beneficial bacteria and reducing the number of harmful bacteria. CONCLUSION: AS-IV reduces the expression of inflammatory factors by inhibiting the PI3K/AKT/mTOR pathway and optimizes the composition of the gut microflora in AIL rats.

Three-Dimensional Computed Tomography Scanning Study of the Superior Labial Artery in Chinese Individuals for Assessing Filler Injection Safety.

BACKGROUND: Lip filler injection is one of the most common minimally invasive cosmetic procedures involving the face; however, vascular complications are not uncommon. The aim of this study was to investigate the anatomy of the superior labial artery (SLA) and provide precise topographic information for dermal filler injection into the lips. METHODS: Computed tomography (CT) scans of 52 cadaveric heads injected with lead oxide were obtained. We then used Mimics software to construct 3D images of the SLA described by a coordinate system based on the bilateral external auditory canal and the left orbit. This study aimed to classify the SLA in the Han Chinese population, measure its diameter at specific points, and determine the thickness of the lip at those points. Ultimately, we utilized a thermal imaging technique to illustrate the course and depth of the SLA within the lip. The objective of this study was to provide safe guidance for clinical injections. RESULTS: In this study, the SLA was successfully identified in all cadavers. The mean overall diameter of the superior labial arteries was 1.36 ± 0.28 mm. The superior labial artery showed a general course from deep to shallow with an average depth of 5.68 ± 1.68 mm from the oral commissure to the midline. CONCLUSIONS: There are anatomical differences in the superior labial arteries among Chinese people. Furthermore, 3D CT images can digitally elucidate the exact positions of the superior labial artery via a coordinate system, improving the safety of upper lip filler injections in clinical settings. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Role of TRAIL Signaling in Cancer: Searching for New Therapeutic Strategies.

Cancer continues to pose a significant threat to global health, with its status as a leading cause of death remaining unchallenged. Within the realm of cancer research, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) stands out as a critical player, having been identified in the 1990s as the tenth member of the TNF family. This review examines the pivotal role of TRAIL in cancer biology, focusing on its ability to induce apoptosis in malignant cells through both endogenous and exogenous pathways. We provide an in-depth analysis of TRAIL's intracellular signaling and intercellular communication, underscoring its potential as a selective anticancer agent. Additionally, the review explores TRAIL's capacity to reshape the tumor microenvironment, thereby influencing cancer progression and response to therapy. With an eye towards future developments, we discuss the prospects of harnessing TRAIL's capabilities for the creation of tailored, precision-based cancer treatments, aiming to enhance efficacy and improve patient survival rates.

The Emerging Role of Ferroptosis in EBV-Associated Cancer: Implications for Cancer Therapy.

Ferroptosis is a novel and iron-dependent form of programmed cell death, which has been implicated in the pathogenesis of various human cancers. EBV is a well-recognized oncogenic virus that controls multiple signaling pathways within the host cell, including ferroptosis signaling. Recent studies show that inducing ferroptosis could be an efficient therapeutic strategy for EBV-associated tumors. This review will firstly describe the mechanism of ferroptosis, then summarize EBV infection and EBV-associated tumors, as well as the crosstalk between EBV infection and the ferroptosis signaling pathway, and finally discuss the role and potential application of ferroptosis-related reagents in EBV-associated tumors.

Fungal Abscess of Anterior Nasal Septum Complicating Maxillary Sinus Fungal Ball Rhinosinusitis Caused by Aspergillus flavus: Case Report and Review of Literature.

Anterior nasal septum abscess is not a rare clinical disease entity. In terms of the etiologies of the disease, bacteria are obviously more common than fungi. Fungal culture and pathological examination are essential for diagnosis of a fungal abscess of the anterior nasal septum and the basis of prescription of antifungal agents. We report a 57-year-old male patient who came to our outpatient clinic due to refractory nasal congestion for 3 weeks despite receiving treatments by a local medical doctor. Radical surgery with postoperative adjuvant radiotherapy for the right buccal cancer was carried out 14 years ago. The patient has diabetes mellitus and the blood sugar level has been well controlled by oral hypoglycemic agents over the past several years. Computed tomography revealed an abscess in the anterior septum along with rhinosinusitis. Incision and drainage of the nasal septum abscess and functional endoscopic sinus surgery were carried out. Fungal culture and pathological examination confirmed a fungal abscess in the anterior nasal septum and fungal ball rhinosinusitis. Antibiotics and an antifungal agent were given, and the postoperative course was uneventful. A dialectical argument was made regarding the causal relationship between the fungal abscess of the anterior nasal septum and maxillary fungal ball sinusitis. A literature review of the previous case reports was carried out to elucidate the immune status of patients of this disease. In order to reach a rapid establishment of a fungal abscess of the anterior nasal septum, clinicians should keep this disease in mind and remain vigilant. An immuno-compromised status is more commonly found in patients with fungal abscess of the anterior nasal septum and is another important characteristic of this disease. Prompt diagnosis and effective treatment are equally important in patients with lower immune status of this kind, and the latter is based on the former.

Surface Analysis of Stainless Steel Electrodes Cleaned by Atmospheric Pressure Plasma.

The Z-pinch device is a critical component in inertial confinement fusion, where stainless steel electrodes must withstand high current densities of up to MA/cm2. Gases and difficult-to-remove impurities adhering to the electrode surfaces can ionize, significantly impacting the device's electrical conductivity efficiency. In this paper, the surface of stainless steel electrodes was subjected to cleaning using a large-area plasma jet under atmospheric pressure. The wettability, chemical composition, and chemical state of the electrode surface were characterized using a water contact angle measuring instrument and X-ray photoelectron spectroscopy (XPS). The cleaning effect under different discharge parameters was systematically analyzed. The results revealed a significant reduction in the content of carbon pollutants on the surface of stainless steel electrodes, decreasing from 62.95% to a minimum of 37.68% after plasma cleaning. Moreover, the water contact angle decreased from 70.76° to a minimum of 29.31°, and the content of water molecules adsorbed on the surface decreased from 17.31% to a minimum of 5.9%. Based on the evolution process of micro-element content and chemical state on the surface of stainless steel electrode, the cleaning process of adhering substances on the surface by atmospheric pressure plasma was analyzed by the layered cleaning model for surface pollutants on stainless steel.

Constructing multi-layer heterogeneous interfaces in liquid metal graphite hybrid powder: Towards microwave absorption enhancement.

Carbon based materials are widely used in the preparation of microwave absorption materials due to their low density, high attenuation loss and large specific surface area. However, their high conductivity usually leads to high reflection loss. In this study, multi-layer heterogeneous interfaces were constructed in liquid metal graphite hybrid powder to reduce reflection loss and enhance microwave absorption performance. Gallium oxide (Ga2O3) layer was formed in Ga coated graphite powder to improve impedance matching and attenuation constant via an annealing treatment. Specifically, the hybrid particles with 50 wt% Ga and being annealed at 120 °C for 2 h have a minimum reflection loss (RLmin) value of -42.68 dB and a maximum effective absorption bandwidth (EAB) of 4.11 GHz at a thickness of 3.3 mm. The hybrid particles not only have multi-layer structures with different electrical conductivity, but also form heterojunctions between different interfaces, which can further enhance dipole and interfacial polarization.

A Nomogram Including Sarcopenia for Predicting Progression-Free Survival in Patients with Localized Papillary Renal Cell Carcinoma: A Retrospective Cohort Study.

BACKGROUND: Because of to the removal of subclassification of papillary renal cell carcinoma (pRCC), the survival prognostification of localized pRCC after surgical treatment became inadequate. Sarcopenia was widely evaluated and proved to be a predictive factor for prognosis in RCC patients. Therefore, we comprehensively investigated the survival prediction of the body composition parameters for localized pRCC. METHODS: Patients pathologically diagnosed with pRCC between February 2012 and February 2022 in our center were enrolled. The body composition parameters, including skeletal muscle index (SMI), subcutaneous adipose tissue (SAT), and perirenal adipose tissue (PRAT), were measured by the images of preoperative computed tomography (CT). The primary outcome was set as progression-free survival (PFS), and the cutoff values of body composition parameters were calculated by using the Youden from receiver operating characteristic curve (ROC) curves. Univariate and multivariate Cox proportional regression analyses were performed to explore independent risk factors for survival prediction. Then, significant factors were used to construct a prognostic nomogram. The performance of the nomogram was evaluated by Harrell's C-index, calibration curves and time-dependent ROC curves. RESULTS: A total of 105 patients were enrolled for analysis. With a median follow-up time of 30.48 months, 25 (23.81%) patients experienced cancer progression. The percentage of sarcopenia was 74.29%. Univariate Cox analysis identified that gender, PRAT, SAT, skeletal muscle (SM), sarcopenia, surgical technique, and tumor diameter were associated with progression. Further multivariate analysis showed that sarcopenia (hazard ratio [HR] 0.15, 95% confidence interval [CI] 0.03-0.66), SAT (HR 6.36, 95% CI 2.39-16.93), PRAT (HR 4.66, 95% CI 1.77-12.27), tumor diameter (HR 0.35, 95% CI 0.14-0.86), and surgical technique (HR 2.85, 95% CI 1.06-7.64) were independent risk factors for cancer progression. Then, a prognostic nomogram based on independent risk factors was constructed and the C-index for progression prediction was 0.831 (95% CI 0.761-0.901), representing a reasonable discrimination, the calibration curves, and the time-dependent ROC curves verified the good performance of the nomogram. CONCLUSIONS: A prognostic nomogram, including sarcopenia, SAT, PRAT, tumor diameter, and surgical technique, was constructed to calculate the probability of progression for localized pRCC patients and needs further external validation for clinical use in the future.

Characterization and noncovalent inhibition of the K63-deubiquitinase activity of SARS-cov-2 PLpro.

SARS-CoV-2 papain-like protease (PLpro) could facilitate viral replication and host immune evasion by respectively hydrolyzing viral polyprotein and host ubiquitin conjugates, thereby rendering itself as an important antiviral target. Yet few noncovalent PLpro inhibitors of SARS-CoV-2 have been reported with improved directed towards pathogenic deubiquitinating activities inhibition. Herein, we report that coronavirus PLpro proteases have distinctive substrate bias and are conserved to deubiquitylate K63-linked polyubiquitination, thereby attenuating host type I interferon response. We identify a noncovalent compound specifically optimized towards halting the K63-deubiquitinase activity of SARS-CoV-2 PLpro, but not other coronavirus (CoV) counterparts or host deubiquitinase. Contrasting with GRL-0617, a SARS-CoV-1 PLpro inhibitor, SIMM-036 is 50-fold and 7-fold (half maximal inhibitory concentration (IC50)) more potent to inhibit viral replication during SARS-CoV-2 infection and restore the host interferon-ß (IFN-ß) response in human angiotensin-converting enzyme 2 (hACE2)-HeLa cells, respectively. Structure-activity relationship (SAR) analysis further reveals the importance of BL2 groove of PLpro, which could determine the selectivity of K63-deubiquitinase activity of the enzyme.