Inhibition of PIKFYVE kinase interferes ESCRT pathway to suppress RNA virus replication.

Endosomal sorting complex required for transport (ESCRT) is essential in the functional operation of endosomal transport in envelopment and budding of enveloped RNA viruses. However, in nonenveloped RNA viruses such as enteroviruses of the Picornaviridae family, the precise function of ESCRT pathway in viral replication remains elusive. Here, we initially evaluated that the ESCRT pathway is important for viral replication upon enterovirus 71 (EV71) infection. Furthermore, we discovered that YM201636, a specific inhibitor of phosphoinositide kinase, FYVE finger containing (PIKFYVE) kinase, significantly suppressed EV71 replication and virus-induced inflammation in vitro and in vivo. Mechanistically, YM201636 inhibits PIKFYVE kinase to block the ESCRT pathway and endosomal transport, leading to the disruption of viral entry and replication complex in subcellular components and ultimately repression of intracellular RNA virus replication and virus-induced inflammatory responses. Further studies found that YM201636 broadly represses the replication of other RNA viruses, including coxsackievirus B3 (CVB3), poliovirus 1 (PV1), echovirus 11 (E11), Zika virus (ZIKV), and vesicular stomatitis virus (VSV), rather than DNA viruses, including adenovirus 3 (ADV3) and hepatitis B virus (HBV). Our findings shed light on the mechanism underlying PIKFYVE-modulated ESCRT pathway involved in RNA virus replication, and also provide a prospective antiviral therapy during RNA viruses infections.

The roles of critical pro-inflammatory cytokines in the drive of cytokine storm during SARS-CoV-2 infection.

In patients with severe COVID-19, acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS), and even mortality can result from cytokine storm, which is a hyperinflammatory medical condition caused by the excessive and uncontrolled release of pro-inflammatory cytokines. High levels of numerous crucial pro-inflammatory cytokines, such as interleukin-1 (IL-1), IL-2, IL-6, tumor necrosis factor-α, interferon (IFN)-γ, IFN-induced protein 10 kDa, granulocyte-macrophage colony-stimulating factor, monocyte chemoattractant protein-1, and IL-10 and so on, have been found in severe COVID-19. They participate in cascade amplification pathways of pro-inflammatory responses through complex inflammatory networks. Here, we review the involvements of these critical inflammatory cytokines in SARS-CoV-2 infection and discuss their potential roles in triggering or regulating cytokine storm, which can help to understand the pathogenesis of severe COVID-19. So far, there is rarely effective therapeutic strategy for patients with cytokine storm besides using glucocorticoids, which is proved to result in fatal side effects. Clarifying the roles of key involved cytokines in the complex inflammatory network of cytokine storm will help to develop an ideal therapeutic intervention, such as neutralizing antibody of certain cytokine or inhibitor of some inflammatory signal pathways.

A vaccine delivery system promotes strong immune responses against SARS-CoV-2 variants.

Global coronavirus disease 2019 (COVID-19) pandemics highlight the need of developing vaccines with universal and durable protection against emerging SARS-CoV-2 variants. Here we developed an extended-release vaccine delivery system (GP-diABZI-RBD), consisting the original SARS-CoV-2 WA1 strain receptor-binding domain (RBD) as the antigen and diABZI stimulator of interferon genes (STING) agonist in conjunction with yeast ß-glucan particles (GP-diABZI) as the platform. GP-diABZI-RBD could activate STING pathway and inhibit SARS-CoV-2 replication. Compared to diABZI-RBD, intraperitoneal injection of GP-diABZI-RBD elicited robust cellular and humoral immune responses in mice. Using SARS-CoV-2 GFP/ΔN transcription and replication-competent virus-like particle system (trVLP), we demonstrated that GP-diABZI-RBD-prototype vaccine exhibited the strongest and durable humoral immune responses and antiviral protection; whereas GP-diABZI-RBD-Omicron displayed minimum neutralization responses against trVLP. By using pseudotype virus (PsVs) neutralization assay, we found that GP-diABZI-RBD-Prototype, GP-diABZI-RBD-Delta, and GP-diABZI-RBD-Gamma immunized mice sera could efficiently neutralize Delta and Gamma PsVs, but had weak protection against Omicron PsVs. In contrast, GP-diABZI-RBD-Omicron immunized mice sera displayed the strongest neutralization response to Omicron PsVs. Taken together, the results suggest that GP-diABZI can serve as a promising vaccine delivery system for enhancing durable humoral and cellular immunity against broad SARS-CoV-2 variants. Our study provides important scientific basis for developing SARS-CoV-2 VOC-specific vaccines.

Highly effective remediation of high arsenic-bearing wastewater using aluminum-containing waste residue.

Wastewater from non-ferrous metal smelting is known as one of the most dangerous sources of arsenic (As) due to its high acidity and high arsenic content. Herein, we propose a new environmental protection process for the efficient purification and removal of arsenic from wastewater by the formation of an AlAsO4@silicate core-shell structure based on the characteristics of aluminum-containing waste residue (AWR). At room temperature, the investigation with AWR almost achieved 100% As removal efficiency from wastewater, reducing the arsenic concentration from 5500 mg/L to 52 µg/L. With Al/As molar ratio of 3.5, the structural properties of AWR provided good adsorption sites for arsenic adsorption, leading to the formation of arsenate and insoluble aluminum arsenate with As. As-containing AWR silicate shells were produced under alkaline conditions, resulting in an arsenic leaching concentration of 1.32 mg/L in the TCLP test. AWR, as an efficient As removal and fixation agent, shows great potential in the treatment of copper smelting wastewater, and is expected to achieve large-scale industrial As removal.

Repurposing of steel rolling sludge: Solvent-free preparation of α-Fe2O3 nanoparticles and its application for As(III/V)-containing wastewater treatment.

Steel rolling sludge (SRS) is the by-product of metallurgical industry with abundant iron content, which needs to be utilized for producing high value-added products. Herein, cost-effective and highly adsorbent α-Fe2O3 nanoparticles were prepared from SRS via a novel solvent-free method and applied to treat As(III/V)-containing wastewater. The structure of the prepared nanoparticles was observed to be spherical with a small crystal size (12.58 nm) and high specific surface area (145.03 m2/g). The nucleation mechanism of α-Fe2O3 nanoparticles and the effect of crystal water were investigated. More importantly, compared with the traditional methods of preparation cost and yield, this study was found to have excellent economic benefits. The adsorption results indicated that the adsorbent could effectively remove arsenic over a wide pH range, and the optimal performance of nano adsorbent for As(III) and As(V) removal was observed at pH 4.0-9.0 and 2.0-4.0, respectively. The adsorption process was consistent with pseudo-second-order kinetic and Langmuir isothermal model. The maximum adsorption capacity (qm) of adsorbent for As(III) and As(V) was 75.67 mg/g and 56.07 mg/g, respectively. Furthermore, α-Fe2O3 nanoparticles exhibited great stability, and qm remained at 64.43 mg/g and 42.39 mg/g after five cycles. Particularly, the As(III) was removed by forming inner-sphere complexes with the adsorbent, and it partially oxidized to As(V) during this process. In contrast, the As(V) was removed by electrostatic adsorption and reaction with -OH on the adsorbent surface. Overall, resource utilization of SRS and the treatment of As(III)/(V)-containing wastewater in this study are in line with the current developments in the environmental and waste-to-value research.

Eco-friendly strategy for preparation of high-purity silica from high-silica IOTs using S-HGMS coupling with ultrasound-assisted fluorine-free acid leaching technology.

Iron ore tailings (IOTs), a typical hazardous solid waste, seriously threaten human health and the ecological environment. However, the abundance of quartz, particularly in high-silica IOTs, renders them useful. Yet, state-of-the-art technologies have rarely reported the preparation of high-purity silica from high-silicon IOTs. Thus, this study proposed an eco-friendly technology for producing high-purity silica from high-silica IOTs through the coupling of superconducting high gradient magnetic separation (S-HGMS) preconcentration with leaching followed by the use of ultrasound-assisted fluorine-free acid solution. Following an analysis of the separation index and chemical composition, the optimum conditions for the quartz preconcentration were determined as a magnetic flow ratio of 0.068 T s/m, a slurry flow velocity of 500 mL/min, and a pulp concentration of 40 g/L. Consequently, the SiO2 grade increased from 69.32% in the raw sample to 93.12% in quartz concentrate following the application of S-HGMS, with the recovery reaching 45.24%. X-ray diffraction, vibrating sample magnetometer, and scanning electron microscope analyses indicated that quartz was effectively preconcentrated from the tailings by S-HGMS. Subsequently, employing the "ultrasound-assisted fluorine-free acid leaching process," impurity elements were removed and high-purity silica was produced. Under optimal leaching conditions, the SiO2 purity of silica sand increased to 97.42%. Following a three-stage acid leaching process with 4 mol/LHCl +2 mol/LH2C2O4, the removal efficiency of Al, Ca, Fe, and Mg exceeded 97% for all cases, and the SiO2 purity in high-purity silica reached 99.93%. Thus, this study proposes a new strategy for the preparation of high-purity quartz from IOTs, which facilitated the effective realization of the high-value utility of the tailings. Furthermore, it provides a theoretical basis for the industrial application of IOTs, which is of great scientific significance and practical application value.

Co-utilization of iron ore tailings and coal fly ash for porous ceramsite preparation: Optimization, mechanism, and assessment.

Maximizing the utilization of industrial by-products, such as iron ore tailings (IOTs) and coal fly ash (CFA), is crucial toward sustainable development. This study provides a meticulous insight into the optimization, mechanism, and assessment of the co-utilization of IOTs and CFA for the preparation of porous ceramsite. Micro-CT results revealed that the prepared ceramsite exhibited an exceptional porosity, peaking at 56.98%, with a wide range of pore diameters (3.55-959.10 µm) under optimal conditions (IOTs content at 76%, preheating at 550 °C for 15 min, and sintering at 1177 °C for 14 min), while maintaining good mechanical properties (water adsorption of 1.28%, comprehensive strength of 8.75 MPa, apparent density of 1.37 g/cm3, and bulk density of 0.62 g/cm3). The primary parameters affecting the porosity were identified and ranked as follows: sintering temperature > IOTs content > sintering time. The formation and growth of pores could be attributed to the equilibrium relationship between the liquid-phase surface tension and the gas expansion force, accompanied by pore wall thinning and pore merging. Notably, the prepared ceramsite is both ecologically feasible and economically rewarding, boasting a profit margin of 9.47 $/ton. The comprehensive life cycle assessment (LCA) conducted further highlights the potential of its large-scale implementation for promoting sustainable development. This study provides an innovative strategy for the co-utilization of IOTs and CFA, with advantages such as cost-effectiveness, ecological feasibility and scalability of production.

Chloride converts lead slag into a bifunctional material to remove heavy metals.

Efficient and safe removal of arsenic and lead from industrial wastewater is essential for ecological protection. In this study, we developed a novel method using lead slag as a purifying agent and sodium chloride as a reinforcing agent to remove arsenic and lead from industrial wastewater. Through a combination of experiments and simulations, we elucidated the mechanisms involved in this reaction. The initial concentrations of As and Pb ions in the industrial wastewater were 4333 and 188 mg/L, respectively. After the reaction at 25 °C and a pH ranging from 9.7 to 10, the concentrations of arsenic and lead were reduced to 4.9 mg/L and 0.008 mg/L, respectively, achieving a removal rate of 99.9%. Our experimental results demonstrated that Pb2+ and AsO43- ions released from the lead slag and industrial wastewater reacted with Cl- ions to form Pb5(AsO4)3Cl precipitates, thus effectively eliminating a significant amount of As and Pb species. Simulation studies indicated that Pb5(AsO4)3Cl exhibited exceptional stability below 400 °C and could be directly stored. Additionally, the lead slag, which is rich in silica, played a crucial role in removing and stabilizing As and Pb ions. Under alkaline conditions, silica encapsulated the As and Pb species, adhering to the surface of the Pb-As co-precipitates and forming dense, irregular, small particles with internal and external structures that impeded the efflux of As and Pb ions. This phenomenon was confirmed through scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The kinetics of As and Pb ion removal was consistent with the pseudo-second-order kinetic model, indicating that the removal process was primarily governed by chemical interactions. Lead slag exhibits significant potential and advantages in the removal of As and Pb. This innovative method offers an effective approach to address heavy metal contamination in industrial wastewater, thus contributing to ecological protection.

Optimization of loop-mediated isothermal amplification (LAMP) assay for robust visualization in SARS-CoV-2 and emerging variants diagnosis.

Loop-mediated isothermal amplification (LAMP) is widely used in detection of pathogenic microorganisms including SARS-CoV-2. However, the performance of LAMP assay needs further exploration in the emerging SARS-CoV-2 variants test. Here, we design serials of primers and select an optimal set for LAMP-based on SARS-CoV-2 N gene for a robust and visual assay in SARS-CoV-2 diagnosis. The limit of detectable template reaches 10 copies of N gene per 25 µL reaction at isothermal 58℃ within 40 min. Importantly, the primers for LAMP assay locate at 12 to 213 nt of N gene, a highly conservative region, which serves as a compatible test in emerging SARS-CoV-2 variants. Comparison to a commercial qPCR assay, this LAMP assay exerts the high viability in diagnosis of 41 clinical samples. Our study optimizes an advantageous LAMP assay for colorimetric detection of SARS-CoV-2 and emerging variants, which is hopeful to be a promising test in COVID-19 surveillance.

Uhrf1-Mediated Tnf-α Gene Methylation Controls Proinflammatory Macrophages in Experimental Colitis Resembling Inflammatory Bowel Disease.

Macrophages drive the pathological process of inflammatory bowel diseases (IBD) mostly by secreting proinflammatory cytokines, such as Tnf-α. Recent studies have indicated the association between epigenetic modifications and macrophage functions. However, epigenetic mechanisms regulating macrophages' functional involvement in IBD remain unknown. In this study, we investigated whether the epigenetic regulator Uhrf1 plays a role in innate immunity by functionally regulating macrophages in intestines. We employed two transgenic strains of mice (one with Uhrf1 deficiency in macrophages [Uhrf1fl/flLyz2-Cre mice] and the other with the two mutations at Uhrf1's DNA methylation regulatory site [Uhrf1YP187/188AA mice]) to assess their susceptibility to dextran sodium sulfate-induced colitis. We examined the cytokines derived from Uhrf1fl/flLyz2-Cre and Uhrf1YP187/188AA macrophages in response to LPS stimulation. We also analyzed the effects of proinflammatory cytokines on Uhrf1 expression in macrophages. The data demonstrated that Uhrf1 deficiency and Uhrf1YP187/188AA mutation resulted in severe colitis in the dextran sodium sulfate-treated mice. In vitro analysis revealed the hypomethylation of Tnf-α promoter and the increased Tnf-α expression in Uhrf1fl/flLyz2-Cre and Uhrf1YP187/188AA macrophages in response to LPS stimulation, and anti-Tnf-α therapy implied the key role of Tnf-α to the aggravated colitis in Uhrf1-deficient mice. Exogenous Tnf-α destabilized Uhrf1 protein through ubiquitination-mediated protein degradation, triggering macrophage activation. In conclusion, we identified that Uhrf1-mediated DNA methylation controls Tnf-α expression of macrophages in the experimental colitis resembling IBD. The epigenetic mechanisms that activate macrophages may provide new therapeutic targets for IBD treatment.

A Crop Canopy Localization Method Based on Ultrasonic Ranging and Iterative Self-Organizing Data Analysis Technique Algorithm.

To protect crops from diseases and increase yields, chemical agents are applied by boom sprayers. To achieve the optimal effect, the boom and the crop canopy should be kept at an appropriate distance. So, it is crucial to be able to distinguish the crop canopy from other plant leaves. Based on ultrasonic ranging, this paper adopts the fuzzy iterative self-organizing data analysis technique algorithm to identify the canopy location. According to the structural characteristics of the crop canopy, based on fuzzy clustering, the algorithm can dynamically adjust the number and center of clusters so as to get the optimal results. Therefore, the distances from the sensor to the canopy or the ground can be accurately acquired, and the influence of lower leaves on the measurement results can be alleviated. Potted corn plants from the 3-leaf stage to the 6-leaf stage were tested on an experiment bench. The results showed that the calculated distances from the sensor to the canopy using this method had good correlation with the manually measured distances. The maximum error of calculated values appeared at the 3-leaf stage. With the growth of plants, the error of calculated values decreased. The increased sensor moving speeds led to increased error due to the reduced data points. From the 3-leaf stage to the 5-leaf stage, the distances from the sensor to the ground can also be obtained at the same time. The method proposed in this paper provides a practical resolution to localize the canopy for adjusting the height of sprayer boom.

Inducible interleukin 32 (IL-32) exerts extensive antiviral function via selective stimulation of interferon λ1 (IFN-λ1).

Interleukin (IL)-32 has been recognized as a proinflammatory cytokine that participates in responses to viral infection. However, little is known about how IL-32 is induced in response to viral infection and the mechanisms of IL-32-mediated antiviral activities. We discovered that IL-32 is elevated by hepatitis B virus (HBV) infection both in vitro and in vivo and that HBV induced IL-32 expression at the level of both transcription and post-transcription. Furthermore, microRNA-29b was found to be a key factor in HBV-regulated IL-32 expression by directly targeting the mRNA 3'-untranslated region of IL-32. Antiviral analysis showed that IL-32 was not sufficient to alter HBV replication in HepG2.2.15 cells. To mimic the viremic phase of viral infection, freshly isolated peripheral blood mononuclear cells were treated with IL-32γ, the secretory isoform, and the supernatants were used for antiviral assays. Surprisingly, these supernatants exhibited extensive antiviral activity against multiplex viruses besides HBV. Thus, we speculated that the IL-32γ-treated peripheral blood mononuclear cells produced and secreted an unknown antiviral factor. Using antibody neutralization assays, we identified the factor as interferon (IFN)-λ1 and not IFN-α. Further studies indicated that IL-32γ effectively inhibited HBV replication in a hydrodynamic injection mouse model. Clinical data showed that elevated levels of IFN-λ1 both in serum and liver tissue of HBV patients were positively correlated to the increased levels of IL-32. Our results demonstrate that elevated IL-32 levels during viral infection mediate antiviral effects by stimulating the expression of IFN-λ1.

Preparation of high-purity SiO2 by S-HGMS coupled with mixed-acid leaching: A case study on hematite tailings from Ansteel, China.

Hematite tailings (HTs) are rich in silica and are used as replacements for fine aggregates in the preparation of construction materials. However, there is scope for a more effective utilization of the valuable elements present in HTs. In this paper, a process for preparing high-purity SiO2 using HTs procured from Ansteel (China) is proposed. HTs were treated using the superconducting high-gradient magnetic separation (S-HGMS) technology, where the silica as part of the nonmagnetic fraction was obtained in the form of a high-silica concentrate, which was then subjected to mixed-acid leaching to dissolve impurities to achieve refined purification. The optimum process conditions for S-HGMS were determined, and the response surface methodology was applied to optimize the process parameters of the mixed-acid leaching process. The process indicators of the mixed-acid leaching step included the leaching time, leaching temperature, and molar ratio of the mixed acids. The optimum process conditions for S-HGMS were as follows: the magnetic strength-to-velocity ratio in the weak magnetic separation stage was set to 0.034 T·s/m whereas it was maintained at 0.076 T·s/m in the strong magnetic separation stage; the pulp concentration was 40 g/L, the pulp velocity was 500 mL/min, and the dispersant concentration was 1 mg/g. Under these conditions, the high-silica pulp was processed. The corresponding SiO2 grade increased from 71.788 % to 95.260 %, and its recovery and yield reached 56.330 % and 42.450 %, respectively. The SiO2 content in the sample increased from 95.260 % to 99.961 %. Further, the mechanisms of the S-HGMS and mixed-acid leaching were revealed. The proposed process is environmentally friendly and operationally inexpensive. It can reduce the amount of HTs by 42.450 %, and the obtained high-purity silica product has high economic value and good industrialization prospects.

The role of inflammasome in chronic viral hepatitis.

Infections of hepatotropic viruses cause a wide array of liver diseases including acute hepatitis, chronic hepatitis and the consequently developed cirrhosis and hepatocellular carcinoma (HCC). Among the five classical hepatotropic viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV) usually infect human persistently and cause chronic hepatitis, leading to major troubles to humanity. Previous studies have revealed that several types of inflammasomes are involved in the infections of HBV and HCV. Here, we summarize the current knowledge about their roles in hepatitis B and C. NLRP3 inflammasome can be activated and regulated by HBV and HCV. It is found to exert antiviral function or mediates inflammatory response in viral infections depending on different experimental models. Besides NLRP3 inflammasome, IFI16 and AIM2 inflammasomes participate in the pathological process of hepatitis B, and NALP3 inflammasome may sense HCV infection in hepatocytes. The inflammasomes affect the pathological process of viral hepatitis through its downstream secretion of inflammatory cytokines interleukin-1ß (IL-1ß) and IL-18 or induction of pyroptosis resulting from cleaved gasdermin D (GSDMD). However, the roles of inflammasomes in different stages of viral infection remains mainly unclear. More proper experimental models of viral hepatitis should be developed for specific studies in future, so that we can understand more about the complexity of inflammasome regulation and multifunction of inflammasomes and their downstream effectors during HBV and HCV infections.

Epigenetic changes mediated by microRNA miR29 activate cyclooxygenase 2 and lambda-1 interferon production during viral infection.

Lambda-1 interferon (IFN-λ1) and cyclooxygenase-2 (COX-2) were reported to play an important role in host antiviral defense. However, the mechanism by which IFN-λ1 and COX2 are activated and modulated during viral infection remains unclear. In this study, we found that expression of both circulating IFN-λ1 and COX2-derived prostaglandin E2 (PGE2) was coordinately elevated in a cohort of influenza patients compared to healthy individuals. Expression of IFN-λ1 was blocked by a selective COX2 inhibitor during influenza A virus infection in A549 human lung epithelial cells but enhanced by overexpression of COX2, indicating that the production of IFN-λ1 is COX2 dependent. COX2 was able to increase IFN-λ1 expression by promoting NF-κB binding to the enhancer in the IFN-λ1 promoter. We found that epigenetic changes activate COX2 expression and PGE2 accumulation during viral infection. The expression of DNA methyltransferase 3a (DNMT3a) and DNMT3b, but not that of DNMT1, was downregulated following influenza A virus infection in both A549 cells and peripheral blood mononuclear cells (PBMCs). We showed that microRNA miR29 suppresses DNMT activity and thus induces expression of COX2 and PGE2. Furthermore, miR29 expression was elevated 50-fold in virally infected A549 cells and 10-fold in PBMCs from influenza patients, compared to expression after mock infection of A549 cells or in healthy individuals, respectively. Activation of the protein kinase A signaling pathway and phosphorylation of CREB1 also contributed to COX2 expression. Collectively, our work defines a novel proinflammatory cascade in the control of influenza A virus infection.

In Memory of the Virologist Jianguo Wu, 1957-2022.

It is with deep sorrow that we mourn the passing of the virologist Professor Jianguo Wu [...].

Recycling lead from copper plant residue (CPR) using brine leaching - Precipitation - Calcination process.

Copper plant residue (CPR) is a hazardous industrial by-product possessing both high toxicity and valuable metal content, necessitating its high value-added utilization. Traditional practices in smelters involve stockpiling and landfilling of CPR, leading to substantial land occupation and water contamination. This study focused on the preparation of PbO and Pb3O4 using the HCl-NaCl leaching-conversion-thermal decomposition process, employing CPR as the primary raw material. The effect of various leaching process conditions on the metal leaching rate was explored. A maximum lead leaching rate of 87.65% was achieved under optimal conditions including leaching temperature, liquid-solid ratio, leaching time, HCl molar concentration, NaCl mass concentration, and particle size. The lead content in the leachate was 15.85 g/L. Experimental data indicated that ash diffusion control served as the rate-limiting step in the HCl-NaCl leaching process. The apparent activation energy was determined to be 18.374 kJ mol-1, with a reaction order of 0.8986 concerning the HCl concentration and an L/S ratio of 0.8124. Additionally, response surface methodology enabled the determination of technological parameters for refining PbCl2 into PbCO3 precursors, yielding a conversion rate exceeding 96.50%. Moreover, the technical indicators of PbO and Pb3O4 obtained through low-temperature thermal decomposition of PbCO3 were investigated. The fabricated PbO and Pb3O4 exhibited purities of 99.65% and 99.26%, respectively, effectively transforming CPR from hazardous waste residue into valuable products. The process ensures the efficient recovery of lead to its maximum extent and promotes residue recycling.

Revision total hip arthroplasty using a fluted, tapered, modular stem follow-up method for a mean of three years: A preliminary study.

Objective: This study aimed to evaluate the results and complications related to revision total hip arthroplasty within a short-to-medium follow up period. Methods: From January 2016 to January 2020, we reviewed 31 prosthetic hip arthroplasty stem revisions using a fluted, tapered modular stem with distal fixation. The median age of the patients was 74.55-79 years. The survival rate was 100%, and there were no re-revisions. The Harris hip score improved from an average of 36.5 ± 7.8 before surgery to 81.8 ± 6.2 at the final follow-up. Results: The average final follow-up was 36 (24-60) months. During this time, there was no periprosthetic infection, no prosthesis loosening or breakage, and no sciatic nerve injury. Complications included four (12.9%) intraoperative fractures and eight (25.8%) dislocations that had no stem fractures. The postoperative limb was lengthened by 17.8 ± 9.8 mm. In most cases, bone regeneration was an early and important finding. Three cases underwent extended trochanteric osteotomy, and bone healing was achieved by the final follow-up. Conclusion: The modular tapered stem reviewed in this study was very versatile, could be used in most femoral revision cases, and allowed for rapid bone reconstruction. However, a long-term follow-up study is needed to confirm these results.

Zika virus non-structural protein 4B interacts with DHCR7 to facilitate viral infection.

Zika virus (ZIKV) evolves non-structural proteins to evade immune response and ensure efficient replication in the host cells. Cholesterol metabolic enzyme 7-dehydrocholesterol reductase (DHCR7) was recently reported to impact innate immune responses in ZIKV infection. However, the vital non-structural protein and mechanisms involved in DHCR7-mediated viral evasion are not well elucidated. In this study, we demonstrated that ZIKV infection facilitated DHCR7 expression. Notably, the upregulated DHCR7 in turn facilitated ZIKV infection and blocking DHCR7 suppressed ZIKV infection. Mechanically, ZIKV non-structural protein 4B (NS4B) interacted with DHCR7 to induce DHCR7 expression. Moreover, DHCR7 inhibited TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) phosphorylation, which resulted in the reduction of interferon-beta (IFN-ß) and interferon-stimulated genes (ISGs) productions. Therefore, we propose that ZIKV NS4B binds to DHCR7 to repress TBK1 and IRF3 activation, which in turn inhibits IFN-ß and ISGs, and thereby facilitating ZIKV evasion. This study broadens the insights on how viral non-structural proteins antagonize innate immunity to facilitate viral infection via cholesterol metabolic enzymes and intermediates.

A programmable DNA nanodevice for colorimetric detection of DNA methyltransferase activity using functionalized hemin/G-quadruplex DNAzyme.

The measurement of DNA methyltransferase (MTase) activity and screening of DNA MTase inhibitors holds significant importance for the diagnosis and therapy of methylation-related illness. Herein, we developed a colorimetric biosensor (PER-FHGD nanodevice) to detect DNA MTase activity by integrating the primer exchange reaction (PER) amplification and functionalized hemin/G-quadruplex DNAzyme (FHGD). By replacing the native hemin cofactor into the functionalized cofactor mimics, FHGD has exhibited significantly improved catalytic efficiency, thereby enhancing the detection performance of the FHGD-based system. The proposed PER-FHGD system is capable of detecting Dam MTase with excellent sensitivity, exhibiting a limit of detection (LOD) as low as 0.3 U/mL. Additionally, this assay demonstrates remarkable selectivity and ability for Dam MTase inhibitors screening. Furthermore, using this assay, we successfully detect the Dam MTase activity both in serum and in E. coli cell extracts. Importantly, this system has the potential to serve as a universal strategy for FHGD-based diagnosis in point-of-care (POC) tests, by simply altering the recognition sequence of the substrate for other analytes.