Covalent immobilization of α-amylase on hollow metal organic framework coated magnetic phase-change microcapsules for the improvement of its thermostability.

Exploring efficient immobilized carrier for α-Amylase (α-Amy) to enhance its thermostability has significant influence in starch related industry. Here, hollow ZIF-8 (HZIF-8) with amino groups coated magnetic phase change microcapsules (PCM) was designed for covalent immobilization of α-Amy. Magnetic PCM consisting n-docosane core and SiO2/Fe3O4 hybrid shell were firstly synthesized. Then, HZIF-8 shell with amino groups was coated and α-Amy was subsequently immobilized through covalent cross-linking strategy. The morphology, chemical structure and magnetic property of PCM@HZIF-8@α-Amy (PCMHA) were comprehensively characterized. Moreover, heat control property of PCMHA was studied with encapsulation efficiency and thermal energy-storage efficiency of 50.55 % and 50.59 %, respectively. Catalytic activity of immobilized α-Amy was fully investigated with Km and Vmax of 2.773 mg/mL and 1.853 µmol/mL·min, respectively. From reusability and storage stability study, immobilized α-Amy not only maintained rather high activity after 9 cycles' reuse, but also exhibited good activity under high salt ion condition after 7 days.

Fracture Behavior and Mechanism of Nb-Si-Based Alloys with Heterogeneous Layered Structure.

Novel Nb-Si-based alloys with heterogeneous layers that have the same composition (Nb-16 at.%Si) but different phase morphologies were designed in this work. Heterogeneous layered structure (HLS) was successfully fabricated in Nb-16Si alloys by layering composite powders after various degrees of mechanical alloying (6 h, 12 h, 18 h, and 24 h) alternately and subsequent spark plasma sintering (SPS). The influence of HLS on the fracture behavior at both room and elevated temperature was investigated via single-edge notched bending (SENB) and high-temperature compression, respectively. The results show that the diversified HLS is obtained by combining hard layers containing fine equiaxed crystals and/or soft ones with coarse lamellar niobium solid solution (Nbss). By affecting the crack propagation in SENB, HLS is favorable for improving the fracture toughness and exhibits a significant increase compared with the corresponding homogenous microstructure. Moreover, for the same HLS, a more excellent performance is achieved when the initial crack is located in the soft layer and extended across the interface to the hard one through crack bridging, crack deflection, crack branching, and shielding effect. Fracture starts in the soft layer (from powders of ball-milled for 12 h) of a 12-24 alloy, and a maximum KQ value (14.89 MPa·mm1/2) is consequently obtained, which is 33.8% higher than that of the homogeneous Nb-16Si alloy. Furthermore, the heterogeneous layered alloys display superior high-temperature compression strength, which is attributable to the dislocation multiplication and fine-grained structure. The proposed strategy in this study offers a promising route for fabricating Nb-Si-based alloys with optimized and improved mechanical properties to meet practical applications.

Investigating the mechanism of rough phenotype in a naturally attenuated Brucella strain: insights from whole genome sequencing.

Objective: Brucellosis, a significant zoonotic disease, not only impacts animal health but also profoundly influences the host immune responses through gut microbiome. Our research focuses on whole genome sequencing and comparative genomic analysis of these Brucella strains to understand the mechanisms of their virulence changes that may deepen our comprehension of the host immune dysregulation. Methods: The Brucella melitensis strain CMCC55210 and its naturally attenuated variant CMCC55210a were used as models. Biochemical identification tests and in vivo experiments in mice verified the characteristics of the strain. To understand the mechanism of attenuation, we then performed de novo sequencing of these two strains. Results: We discovered notable genomic differences between the two strains, with a key single nucleotide polymorphism (SNP) mutation in the manB gene potentially altering lipopolysaccharide (LPS) structure and influencing host immunity to the pathogen. This mutation might contribute to the attenuated strain's altered impact on the host's macrophage immune response, overing insights into the mechanisms of immune dysregulation linked to intracellular survival. Furthermore, we explore that manipulating the Type I restriction-modification system in Brucella can significantly impact its genome stability with the DNA damage response, consequently affecting the host's immune system. Conclusion: This study not only contributes to understanding the complex relationship between pathogens, and the immune system but also opens avenues for innovative therapeutic interventions in inflammatory diseases driven by microbial and immune dysregulation.

Tumor-Agnostic Approvals: Insights and Practical Considerations.

Since the first approval of a tumor-agnostic indication in 2017, a total of seven tumor-agnostic indications involving six drugs have received approval from the FDA. In this paper, the master protocol subteam of the Statistical Methods in Oncology Scientific Working Group, Biopharmaceutical Session, American Statistical Association, provides a comprehensive summary of these seven tumor-agnostic approvals, describing their mechanisms of action; biomarker prevalence; study design; companion diagnostics; regulatory aspects, including comparisons of global regulatory requirements; and health technology assessment approval. Also discussed are practical considerations relating to the regulatory approval of tumor-agnostic indications, specifically (i) recommendations for the design stage to mitigate the risk that exceptions may occur if a treatment is initially hypothesized to be effective for all tumor types and (ii) because drug development continues after approval of a tumor-agnostic indication, recommendations for further development of tumor-specific indications in first-line patients in the setting of a randomized confirmatory basket trial, acknowledging the challenges in this area. These recommendations and practical considerations may provide insights for the future development of drugs for tumor-agnostic indications.

Effect of Ultrasonic Vibration on Microstructure and Fluidity of Aluminum Alloy.

The effect of ultrasonic vibration on the fluidity and microstructure of cast aluminum alloys (AlSi9 and AlSi18 alloys) with different solidification characteristics was investigated. The results show that ultrasonic vibration can affect the fluidity of alloys in both solidification and hydrodynamics aspects. For AlSi18 alloy without dendrite growing solidification characteristics, the microstructure is almost not influenced by ultrasonic vibration, and the influence of ultrasonic vibration on its fluidity is mainly in hydrodynamics aspects. That is, appropriate ultrasonic vibration can improve fluidity by reducing the flow resistance of the melt, but when the vibration intensity is high enough to induce turbulence in the melt, the turbulence will increase the flow resistance greatly and decrease fluidity. However, for AlSi9 alloy, which obviously has dendrite growing solidification characteristics, ultrasonic vibration can influence solidification by breaking the growing α (Al) dendrite, consequently refining the solidification microstructure. Ultrasonic vibration could then improve the fluidity of AlSi9 alloy not only from the hydrodynamics aspect but also by breaking the dendrite network in the mushy zone to decrease flow resistance.

Effect of Cr on Microstructure and Properties of WVTaTiCrx Refractory High-Entropy Alloy Laser Cladding.

WVTaTiCrx (x = 0, 0.25, 0.5, 0.75, 1) refractory high-entropy alloy coatings were prepared on a 42-CrMo steel plate using laser cladding. The purpose of this work is to investigate the effect of the Cr content on the microstructure and properties of the WVTaTiCrx coating. The morphologies and phase compositions of five coatings with different Cr contents were comparatively observed. In addition, the hardness and high-temperature oxidation resistance of the coatings were also analyzed. As a result, with the increase in Cr, the coating grains were more refined. All the coating is mainly composed of the BCC solid-solution phase, which promotes the precipitation of the Laves phase with the increase in Cr. The addition of Cr greatly improves the hardness, high-temperature oxidation resistance and corrosion resistance of the coating. The WVTaTiCr (Cr1) exhibited superior mechanical properties, especially in terms of its exceptional hardness, high-temperature oxidation resistance and outstanding corrosion resistance. The average hardness of the WVTaTiCr alloy coating reaches 627.36 HV. After 50 h of high-temperature oxidation, the oxide weight of WVTaTiCr increases by 5.12 mg/cm2, and the oxidation rate is 0.1 mg/(cm2·h). In 3.5 wt% NaCl solution, the corrosion potential of WVTaTiCr is -0.3198 V, and the corrosion rate is 0.161 mm/a.

Effects of oral immunonutritional supplement on 3-year disease-free survival in gastric cancer patients with pathological stage III after total gastrectomy (CRUCIAL): study protocol of a multicentre, randomised clinical trial.

INTRODUCTION: The nutritional status of patients with gastric cancer (GC) after total gastrectomy continues to deteriorate and lasts a long time after discharge, which is an independent risk factor for mortality. Recent guidelines have recommended appropriate nutritional support after discharge for cancer surgery patients with malnutrition or nutritional risk. The evidence on the efficacy of oral immunonutritional supplement (INS) and its effect on long-term disease-free survival (DFS) in patients with GC is limited. This study was designed to test the hypothesis that oral INS compared to diet alone may improve 3-year DFS of GC patients with pathological stage III after total gastrectomy (Nutrition Risk Screening 2002 score ≥3 at discharge). METHODS AND ANALYSIS: This is a pragmatic, open-label, multicentre, randomised controlled study. 696 eligible GC patients with pathological stage III after total gastrectomy will be randomised in a 1:1 ratio to oral INS group or normal diet group for 6 months. The primary endpoint is 3-year DFS after discharge. The following secondary endpoints will be evaluated: 3-year overall survival; unplanned readmission rate at 3 and 6 months after discharge; quality of life, body mass index and haematological index at 3, 6 and 12 months after discharge; incidence of sarcopenia at 6 and 12 months after discharge; and the tolerance to chemotherapy. The adverse events of oral INS will also be evaluated during the intervention. ETHICS AND DISSEMINATION: This study was approved by the ethics committee of Jinling Hospital, Nanjing University (number 2021NZKY-069-01). The present study may validate the effectiveness of oral immunonutritional therapy in improving 3-year DFS for GC patients with pathological stage III after total gastrectomy for the first time. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: NCT05253716.

Survival of SARS-CoV-2 in artificial seawater and on the surface of inanimate materials.

There is a potential risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread through human contact with seafood and the inanimate materials contaminated by the virus. In this study, we examined the stability of the virus in artificial seawater (ASW) and on the surface of selected materials. SARS-CoV-2 (3.75 log10 TCID50 ) in ASW at 22℃ maintained infectious about 3 days and at 4℃ the virus survived more than 7 days. It should be noticed that viable virus at high titer (5.50 log10 TCID50 ) may survive more than 20 days in ASW at 4℃ and for 7 days at 22℃. SARS-CoV-2 on stainless steel and plastic bag maintained infectious for 3 days, and on nonwoven fabric for 1 day at 22℃. In addition, the virus remained infectious for 9 days on stainless steel and non-woven fabric, and on plastic bag for 12 days at 4℃. It is important to highlight the role of inanimate material surfaces as a source of infection and the necessity for surface decontamination and disinfection.

Ultrasmall Au nanoparticles modified 2D metalloporphyrinic metal-organic framework nanosheets with high peroxidase-like activity for colorimetric detection of organophosphorus pesticides.

Ultrasmall Au nanoparticles (UsAuNPs) in the size range of 4.0-7.0 nm was successfully immobilized on the surface of 2D metalloporphyrinic metal-organic framework nanosheets (2D MOF). Firstly, The obtained hybrid nanomaterial, UsAuNPs/2D MOF, was fully characterized by TEM, HRTEM, element mapping images and XPS. Then, the peroxidase-like activity of UsAuNPs/2D MOF was comparatively studied with other hybrid nanozyme to explore the influence of AuNPs size on peroxidase-like activity. Further, UsAuNPs/2D MOF with outstanding peroxidase-like activity was selected to form ternary cascade enzyme reaction with acetylcholinesterase (AChE) and choline oxidase (ChOx). Based on the inhibitory effect of organophosphorus pesticides on AChE, a fast and sensitive colorimetric method was established for trichlorfon detection with the advantages of simple operation, low detection limit (1.7 µM), good linear range (1.7-42.4 µM) and high accuracy (recovery rate of 96.6-105.3%). Finally, this method was applied to visual analysis of trichlorfon concentration in tomatoes, cucumbers and eggplants.

A genome-wide CRISPR screen identifies host factors that regulate SARS-CoV-2 entry.

The global spread of SARS-CoV-2 is posing major public health challenges. One feature of SARS-CoV-2 spike protein is the insertion of multi-basic residues at the S1/S2 subunit cleavage site. Here, we find that the virus with intact spike (Sfull) preferentially enters cells via fusion at the plasma membrane, whereas a clone (Sdel) with deletion disrupting the multi-basic S1/S2 site utilizes an endosomal entry pathway. Using Sdel as model, we perform a genome-wide CRISPR screen and identify several endosomal entry-specific regulators. Experimental validation of hits from the CRISPR screen shows that host factors regulating the surface expression of angiotensin-converting enzyme 2 (ACE2) affect entry of Sfull virus. Animal-to-animal transmission with the Sdel virus is reduced compared to Sfull in the hamster model. These findings highlight the critical role of the S1/S2 boundary of SARS-CoV-2 spike protein in modulating virus entry and transmission and provide insights into entry of coronaviruses.