Silicon-Containing Thiol-Specific Bioconjugating Reagent.

A new bioconjugation reagent containing silicon has been developed for the selective reaction with thiols. The inclusion of silicon significantly improves chemoselectivity and suppresses retro processes, thereby exceeding the capabilities of traditional reagents. The method is versatile and compatible with a broad range of thiols and unsaturated carbonyl compounds and yields moderate to high results. These reactions can be conducted under biocompatible conditions, thereby making them suitable for protein bioconjugation. The resulting conjugates display good stability in the presence of various biomolecules, which suggests their potential application for the synthesis of antibody-drug conjugates. Furthermore, the presence of a silicon moiety within the conjugated products opens up new avenues for drug release and bridging inorganics with other disciplines. This new class of silicon-containing thiol-specific bioconjugation reagents has significant implications for researchers working in bioanalytical science and medicinal chemistry and leads to innovative opportunities for advancing the field of bioconjugation research and medicinal chemistry.

Evidence from a meta-analysis and systematic review reveals the global prevalence of mild cognitive impairment.

Objective: Mild cognitive impairment (MCI) is a preclinical and transitional stage between healthy ageing and dementia. The purpose of our study was to investigate the recent pooled global prevalence of MCI. Methods: This meta-analysis was in line with the recommendations of Cochrane's Handbook and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020. We conducted a comprehensive search using the PubMed, Embase, Web of Science, CNKI, WFD, VIP, and CBM from their inception to March 1, 2023. Quality assessment was guided by the Agency for Healthcare Research and Quality (AHRQ) methodology checklist. The pooled global prevalence of MCI was synthesized using meta-analysis via random effect model. Subgroup analyses were performed to examine considered factors potentially associated with MCI prevalence. Results: We identified 233 studies involving 676,974 individuals aged above 50 years. All the studies rated as moderated-to-high quality. The overall prevalence of MCI was 19.7% [95% confidence interval (95% CI): 18.3-21.1%]. Subgroup analyses revealed that the global prevalence of MCI increased over time, with a significant rise [32.1% (95% CI: 22.6-41.6%)] after 2019. Additionally, MCI prevalence in hospitals [34.0% (95% CI: 22.2-45.7%)] was higher than in nursing homes [22.6% (95% CI: 15.5-29.8%)] and communities [17.9% (95% CI: 16.6-19.2%)], particularly after the epidemic of coronavirus disease 2019 (COVID-19). Conclusion: The global prevalence of MCI was 19.7% and mainly correlated with beginning year of survey and sample source. The MCI prevalence increased largely in hospitals after 2019 may be related to the outbreak of COVID-19. Further attention to MCI is necessary in the future to inform allocation of health resources for at-risk populations.

Thermal and Humidity Performance Test of Rammed-Earth Dwellings in Northwest Sichuan during Summer and Winter.

Rammed-earth dwellings have a long history in the construction field. It is a natural material that is both green and environmentally friendly. In recent years, the advantages of rammed earth, such as environmental protection, low cost, and recyclability, have attracted considerable attention. In this study, the thermal and humidity physical properties of rammed-earth materials in the northwest Sichuan region, the variation laws of thermal physical parameters, such as the thermal conductivity of rammed-earth under different moisture content conditions, and isothermal moisture absorption and desorption curves were investigated. The results indicated that the thermal physical parameters of the rammed earth measured in the experiment increased with an increase in moisture content, and its moisture absorption performance was better than the moisture release performance in the range of 11.31-97.3% relative humidity. The experimental site, Mianyang City, Sichuan Province, is a subtropical monsoon humid climate zone characterized by warm winters and hot summers with four distinct seasons. In this study, we investigated the hygrothermal coupling transfer of walls, as well as the indoor temperature and humidity changes in new rammed-earth buildings during summer and winter climates. During the test period, the maximum indoor temperature in summer was 35.08 °C, the minimum temperature was 33.76 °C, and the average daily temperature fluctuation was 3.62 °C. In winter, the maximum indoor temperature was 8.59 °C, the minimum temperature was 6.18 °C, and the average daily temperature fluctuation was 1.21 °C. An analysis was performed on the thermal insulation performance of rammed-earth buildings in an extremely high-temperature climate during summer, thermal insulation performance, the thermal-buffering capacity of walls in a low-temperature and high-humidity climate during winter, and thermal and humidity regulation of indoor environments provided by walls during summer and winter. The results showed that the rammed-earth buildings exhibited warmth in winter, coolness in summer, and a more stable and comfortable indoor environment.

Surficial nano-deposition locoregionally yielding bactericidal super CAR-macrophages expedites periprosthetic osseointegration.

Tracking and eradicating Staphylococcus aureus in the periprosthetic microenvironment are critical for preventing periprosthetic joint infection (PJI), yet effective strategies remain elusive. Here, we report an implant nanoparticle coating that locoregionally yields bactericidal super chimeric antigen receptor macrophages (CAR-MΦs) to prevent PJI. We demonstrate that the plasmid-laden nanoparticle from the coating can introduce S. aureus-targeted CAR genes and caspase-11 short hairpin RNA (CASP11 shRNA) into macrophage nuclei to generate super CAR-MΦs in mouse models. CASP11 shRNA allowed mitochondria to be recruited around phagosomes containing phagocytosed bacteria to deliver mitochondria-generated bactericidal reactive oxygen species. These super CAR-MΦs targeted and eradicated S. aureus and conferred robust bactericidal immunologic activity at the bone-implant interface. Furthermore, the coating biodegradability precisely matched the bone regeneration process, achieving satisfactory osteogenesis. Overall, our work establishes a locoregional treatment strategy for priming macrophage-specific bactericidal immunity with broad application in patients suffering from multidrug-resistant bacterial infection.

Alkynone ß-trifluoroborates: A new class of amine-specific biocompatible click reagents.

Amine-targeting reactions that work under biocompatible conditions or in water are green processes that are extremely useful for the synthesis of functional materials and biotherapeutics. Unfortunately, despite the usefulness of this reaction, there are very few good amine-specific click methods reported thus far. Here, we report an amine-specific click reagent using alkynone ß-trifluoroborates as the electrophiles. These boron-containing alkynyl reagents exhibit extremely high chemoselectivity toward amines even in the presence of thiols. The resulting oxaboracycle products are bench-stable, displaying the reactivities of both organoborates and enaminones. Intrinsic advantages of this methodology include benign reaction conditions, operational simplicity, remarkable product stability, and excellent chemoselectivity, which satisfy the criteria of click chemistry and demonstrate the high potential in bioconjugation. Hence, this water-based chemical approach is also applicable to the modification of native amino acids, peptides, and proteins. Ultimately, the essential role of water during the reaction was elucidated.

Mussel-inspired alkaline phosphatase-specific coating on orthopedic implants for spatiotemporal modulating local osteoimmune microenvironment to facilitate osseointegration.

Inadequate initial osseointegration and consequent prosthesis loosening are the most severe complications after artificial arthroplasty. Proper immune responses are crucial for the successful implantation of artificial prostheses. Macrophages are central in osteoimmunomodulation because they exert distinct functions with highly plasticity. Herein, we developed an alkaline phosphatase (ALP) sensitive mussel-inspired coating on orthopedic implants for promoting osseointegration. First, the resveratrol-alendronate complexes were deposited on titanium implant surface through mussel-inspired interfacial interactions. Upon prosthesis implantation, macrophages first polarized towards M1 type to initiate inflammatory responses and bone regeneration. As osteogenesis progresses, increasing amounts of ALP secreted by osteoblasts was cleaved the resveratrol-alendronate complexes. Then, the released resveratrol further promoted osteogenic differentiation of BMSCs and induced locoregional macrophages M2 polarization. Our results demonstrated that the bioinspired osteoimmunomodulation coating remarkably facilitated the prosthesis-bone integration by spatiotemporally modulating macrophages switching from M1 to M2 polarization in response to a real-time healing signal during osteogenesis. In summary, the mussel-inspired osteoimmunomodulation coating technology may provide a new approach for promoting osseointegration after artificial arthroplasty.

Exosome-Functionalized Ti6Al4V Scaffolds Promoting Osseointegration by Modulating Endogenous Osteogenesis and Osteoimmunity.

Periprosthetic bone defects are the most serious problem of revision total hip arthroplasty, which can easily lead to insufficient osteointegration between the prosthesis and host bone. Bone marrow mesenchymal stem cells (BMSCs) and a moderate inflammatory response at the prosthesis-bone interface play an important role in osteointegration. Here, we developed microarc oxide titanium implant loaded engineered exosomes (S-Exos) to promote osseointegration at the prosthesis-bone interface. First, Smurf1-shRNA was transferred into the BMSCs using a viral vector to prepare S-Exos, which were subsequently immobilized to the microarc oxide titanium implant surface with positively charged polyethyleneimine. The immobilized S-Exos could be slowly and uniformly released and subsequently phagocytosed by BMSCs and macrophages. Once the S-Exos were phagocytosed, they could simultaneously activate the BMP/Smad signaling pathway in the BMSCs and promote macrophage M2 polarization, both of which enhance osseointegration. Specifically, this S-Exos coating exhibits a dual effect of promoting osseointegration, including the osseointegration of BMSCs by activating the BMP/Smad signaling pathway and the macrophage M2 polarization promoting osseointegration. In summary, the construction of S-Exos modified microarc oxide titanium implants could provide a new method for promoting osteointegration between the prosthesis and host bone in revision total hip arthroplasty.

Simultaneously promoting adhesion and osteogenic differentiation of bone marrow-derived mesenchymal cells by a functional electrospun scaffold.

Electrospinning is a common technology to construct tissue engineering scaffolds for bone regeneration. However, pure electrospun scaffolds do not enrich seed cells or promote their osteogenic differentiation. Biological functionalization of tissue engineering scaffolds is currently a hot research topic. Therefore, in this study, the bone marrow-derived mesenchymal cells (BM-MSC)-specific affinity peptide E7 and a bone morphogenic protein 2 (BMP-2) mimetic peptide were concomitantly conjugated onto the surface of an electrospun scaffold to construct a functional PEB scaffold. Characterization of PEB scaffolds revealed that both E7 and BMP-2 mimetic peptides were successfully conjugated onto the surface of electrospun scaffolds. With regard to biological activity, the PEB scaffold could synchronously promote adhesion and osteogenic differentiation of BM-MSC as a result of the co-delivery of E7 and BMP-2 mimetic peptides, which proved superior compared with the other three scaffolds. Consequently, the PEB scaffold offers a new concept for the construction of bone tissue engineering scaffolds.

A New Synthetic Aperture Radar (SAR) Imaging Method Combining Match Filter Imaging and Image Edge Enhancement.

In general, synthetic aperture radar (SAR) imaging and image processing are two sequential steps in SAR image processing. Due to the large size of SAR images, most image processing algorithms require image segmentation before processing. However, the existence of speckle noise in SAR images, as well as poor contrast and the uneven distribution of gray values in the same target, make SAR images difficult to segment. In order to facilitate the subsequent processing of SAR images, this paper proposes a new method that combines the back-projection algorithm (BPA) and a first-order gradient operator to enhance the edges of SAR images to overcome image segmentation problems. For complex-valued signals, the gradient operator was applied directly to the imaging process. The experimental results of simulated images and real images validate our proposed method. For the simulated scene, the supervised image segmentation evaluation indexes of our method have more than 1.18%, 11.2% and 11.72% improvement on probabilistic Rand index (PRI), variability index (VI), and global consistency error (GCE). The proposed imaging method will make SAR image segmentation and related applications easier.