Catalyst- and base-free visible light-enabled radical relay trihalomethylation/functional group-migration/carbonylation with CX3SO2Cl.

Herein, we report a visible light-enabled radical trihalomethylation/cyano-migration/carbonylation cascade reaction of 2-hydroxy-2-hex-5-enenitrile with CX3SO2Cl as the CX3-source (X = F, Cl) to obtain 5-oxo-2-(2,2,2-trihaloethyl)pentanenitrile compounds in the absence of a photocatalyst, transition metal and base. This reaction system is also effective to convert (benzo[d]thiazol-2-yl)-pent-4-enol to the corresponding 4-(benzo[d]thiazol-2-yl)-6,6,6-trihalo-hexanone products. These reactions occur under mild conditions, tolerate a wide range of functional groups, and provide alternative approaches for the 1,2-bifunctionalization reaction of unactivated olefins.

Neat1 promotes acute kidney injury to chronic kidney disease by facilitating tubular epithelial cells apoptosis via sequestering miR-129-5p.

Acute kidney injury (AKI) is increasingly identified as a crucial risk factor for progression to CKD. However, the factors governing AKI to CKD progression remain largely unknown. By high-throughput RNA sequencing, we found that Neat1_2, a transcript variant of Neat1, was upregulated in 40-min ischemia/reperfusion injury (IRI), which resulted in the development of renal fibrotic lesions. The upregulation of Neat1_2 in hypoxia-treated TECs was attributed to p53 transcriptional regulation. Gain- and loss-of-function studies, both in vitro and in vivo, demonstrated that Neat1_2 promoted apoptosis of injured TECs induced by IRI and caused tubulointerstitial inflammation and fibrosis. Mechanistically, Neat1_2 shares miRNA response elements with FADD, CASP-8, and CASP-3. Neat1_2 competitively binds to miR-129-5p and prevents miR-129-5p from decreasing the levels of FADD, CASP-8, and CASP-3, and ultimately facilitates TEC apoptosis. Increased expression of Neat1_2 associated with kidney injury and TEC apoptosis was recapitulated in human AKI, highlighting its clinical relevance. These findings suggest that preventing TEC apoptosis by hindering Neat1_2 expression may be a potential therapeutic strategy for AKI to CKD progression.

Visible-Light-Enabled Ph3P/LiI-Promoted Tandem Radical Trifluoromethylation/Cyclization/Iodination of 1,6-Enynes with Togni's Reagent.

We report the visible-light-induced Ph3P/LiI-promoted intermolecular cascade trifluoromethyl radical addition/5-exo-dig cyclization/iodination of 1,6-enynes with Togni's reagent using LiI as the iodine source without the need of the transition metal, oxidant, and base. This reaction promises to be a useful method for the preparation of trifluoromethyl-substituted and vinyl C-I bond-containing pyrrolidines and benzofuran products with good regioselectivity and functional-group tolerance under ambient conditions.

Experimental Study on Magnetic Coupling Piezoelectric-Electromagnetic Composite Galloping Energy Harvester.

In order to solve the demand for low-power microcomputers and micro-electro-mechanical system components for continuous energy supply, a magnetic coupling piezoelectric-electromagnetic composite galloping energy harvester (MPEGEH) is proposed. It is composed of a piezoelectric energy harvester (PEH) and an electromagnetic energy harvester (EEH) coupled by magnetic force. The bistable nonlinear magnetic coupling structure improves the output power of the MPEGEH. The advantages and output performance of the MPEGEH are analyzed. The prototype of the energy harvester is made, and the nonlinear output characteristics under different load resistances are analyzed. Through the experiment on the key parameters of the composite energy harvester, it is found that the higher the coupling degree of the two parts of the MPEGEH, the stronger the nonlinear characteristics and the better the output characteristics. The results show that the onset wind velocity and output power of the MPEGEH are better than the classic galloping piezoelectric energy harvester (CGPEH). At the same wind speed, with the increase in the distance d0 between magnets A and B, the output power of both the PEH and the EEH decreases. When d0 is 37 mm, the output power of the EEH is the largest. The distance s0 between magnets B and C has little influence on the output power of the PEH but has a great influence on the EEH. When s0 is 23 mm, the EEH has the best output characteristics. Compared with the CGPEH, the onset wind velocity is reduced by 28%, and the output power is increased by 136% when the wind speed is 11 m/s.

Impact of COVID-19 pandemic on the professional intention of medical and related students.

BACKGROUND: The outbreak of COVID-19 has led to increased workload and infection risks among medical staff. This situation may influence current medical and health-related students' decision on the choices of their future careers. Hence, this study investigated the impact of COVID-19 on their future career intentions. METHODS: This is a cross-sectional observational study that included medical and health-related students from three universities between October 2020 and January 2021. The study questionnaire was divided into two main sections: Section 1, which comprised students' basic information. And section 2 focused mainly on the impact of COVID-19 pandemic on students' professional intentions. The chi-squared χ2 test was used to compare the responses before and after the pandemic outbreak among Chinese and non-Chinese students. RESULTS: In overall, 1253 students completed the questionnaires. The responses showed that the number of students who preferred clinical medicine, public health, pharmacy and oral medicine increased significantly after the pandemic outbreak. In contrast, the number of students who chose nursing and medical technology decreased significantly. The change mainly occurred in Chinese students, predominantly females. Half of students (50.35%) were more willing to engage in medical and health work after completing their current program. Also, 36.39% of students felt that knowledge was too limited in the pandemic's face and would like to continue studying after graduation to gain more knowledge. Due to the pandemic, 34.18% of students would like a future workplace near their hometown, and 19.63% preferred to work in urban areas. CONCLUSION: The COVID-19 outbreak impacted current medical and health-related students' career planning on their future workplaces and employment time choices. Additionally, the pandemic influenced the intention of Chinese students in choosing their future careers. This study provided the basis for the policymaking, specialty setting of colleges and supplied the medical health department's talent reserve information.

Deformability and size-based cancer cell separation using an integrated microfluidic device.

Cell sorting by filtration techniques offers a label-free approach for cell separation on the basis of size and deformability. However, filtration is always limited by the unpredictable variation of the filter hydrodynamic resistance due to cell accumulation and clogging in the microstructures. In this study, we present a new integrated microfluidic device for cell separation based on the cell size and deformability by combining the microstructure-constricted filtration and pneumatic microvalves. Using this device, the cell populations sorted by the microstructures can be easily released in real time for subsequent analysis. Moreover, the periodical sort and release of cells greatly avoided cell accumulation and clogging and improved the selectivity. Separation of cancer cells (MCF-7, MDA-MB-231 and MDA231-LM2) with different deformability showed that the mixture of the less flexible cells (MCF-7) and the flexible cells (MDA-MB-231 and MDA231-LM2) can be well separated with more than 75% purity. Moreover, the device can be used to separate cancer cells from the blood samples with more than 90% cell recovery and more than 80% purity. Compared with the current filtration methods, the device provides a new approach for cancer cell separation with high collection recovery and purity, and also, possesses practical potential to be applied as a sample preparation platform for fundamental studies and clinical applications.

Multifunctional surface of the nano-morphic PEEK implant with enhanced angiogenic, osteogenic and antibacterial properties.

Polyetheretherketone (PEEK) is a high-performance polymer suitable for use in biomedical coatings. The implants based on PEEK have been extensively studied in dental and orthopedic fields. However, their inherent inert surfaces and poor osteogenic properties limit their broader clinical applications. Thus, there is a pressing need to produce a multifunctional PEEK implant to address this issue. In response, we developed sulfonated PEEK (sPEEK)-Cobalt-parathyroid hormone (PTH) materials featuring multifunctional nanostructures. This involved loading cobalt (Co) ions and PTH (1-34) protein onto the PEEK implant to tackle this challenge. The findings revealed that the controlled release of Co2+ notably enhanced the vascular formation and the expression of angiogenic-related genes, and offered antimicrobial capabilities for sPEEK-Co-PTH materials. Additionally, the sPEEK-Co-PTH group exhibited improved cell compatibility and bone regeneration capacity in terms of cell activity, alkaline phosphatase (ALP) staining, matrix mineralization and osteogenic gene expression. It surpassed solely sulfonated and other functionalized sPEEK groups, demonstrating comparable efficacy even when compared to the titanium (Ti) group. Crucially, animal experiments also corroborated the significant enhancement of osteogenesis due to the dual loading of cobalt ions and PTH (1-34). This study demonstrated the potential of bioactive Co2+ and PTH (1-34) for bone replacement, optimizing the bone integration of PEEK implants in clinical applications.

Effects of combined modification of sulfonation, oxygen plasma and silane on the bond strength of PEEK to resin.

OBJECTIVE: This study aimed to evaluate the combined effects of sulfonation, non-thermal oxygen plasma and silane on the shear bond strength (SBS) of PEEK to resin materials. MATERIALS AND METHODS: Two hundred and eighty specimens were randomly divided into four groups: (A) untreated; (B) sulfonation for 60 s; (C) oxygen plasma for 20 min; (D) sulfonation for 60 s and oxygen plasma for 20 min. According to the instructions, 120 samples (N = 30) were coated with silane, adhesive, and resin composites. Each group of bonding specimens was divided into two subgroups (n = 15) to measure immediate and post-aging SBS. The surface morphology and the interface between the samples and adhesive were analyzed through SEM. Physicochemical characteristics of the surface and mechanical properties were determined through XPS, FTIR, light interferometry, contact angle measurement, and three-point bending tests. RESULTS: Sulfonation produced a porous layer of approximately 20 µm thickness on the surface, and the oxygen plasma increased the O/C ratio and oxygen-containing groups of the sample surface. After coating with silane, the SBS values of sulfonated PEEK and plasma-treated PEEK increased (9.96 and 10.72 MPa, respectively), and dual-modified PEEK exhibited the highest SBS value (20.99 MPa), which was significantly higher than that of blank group (p > 0.01). After 10,000 thermal cycles, the dual-modified PEEK still displayed a favorable SBS (18.68 MPa). SIGNIFICANCE: Sulfonation strengthened the mechanical interlocking between PEEK and the resin while oxygen plasma established a chemical bonding between silane and PEEK. This dual modification of the surface microstructure and chemical state synergistically improved the bond strength of PEEK to resin and resulted in considerable long-term effects.

Enhancing bioactivity and biocompatibility of polyetheretherketone (PEEK) for dental and maxillofacial implants: A novel sequential soaking process.

Polyetheretherketone (PEEK) exhibits excellent biocompatibility, fatigue resistance, and an elastic modulus similar to bone, presenting broad application prospects in the field of dental and maxillofacial implants. However, the bioinertness of PEEK limits its applications. In this study, we developed a method to generate biocompatible and bioactive PEEK through a simple sequential soaking process, aimed at inducing bone differentiation and enhancing antibacterial properties. Initially, a three-dimensional (3D) porous network was introduced on the PEEK surface by soaking in concentrated sulfuric acid and water. Subsequently, the sulfonated PEEK surface was treated with oxygen plasma, followed by immersion in a dopamine solution to coat a polydopamine (PDA) layer. Finally, polydopamine phosphate ester-modified 3D porous PEEK was obtained through the reaction of phosphoryl chloride with surface phenolic hydroxyl groups. Systematic studies were conducted using scanning electron microscopy, X-ray photoelectron spectroscopy, water contact angle analysis, cell proliferation and adhesion, osteogenic gene expression detection, alkaline phosphatase staining, alizarin red staining, and bacterial culture. Overall, compared to unmodified PEEK, the modified PEEK significantly enhanced in vitro cell proliferation and adhesion, osteogenic differentiation, and antibacterial properties. The simple surface modification measures combined in this study may represent a promising technology and could facilitate the application of PEEK in dental and maxillofacial implants.

Transdifferentiation of fibroblasts into muscle cells to constitute cultured meat with tunable intramuscular fat deposition.

Current studies on cultured meat mainly focus on the muscle tissue reconstruction in vitro, but lack the formation of intramuscular fat, which is a crucial factor in determining taste, texture, and nutritional contents. Therefore, incorporating fat into cultured meat is of superior value. In this study, we employed the myogenic/lipogenic transdifferentiation of chicken fibroblasts in 3D to produce muscle mass and deposit fat into the same cells without the co-culture or mixture of different cells or fat substances. The immortalized chicken embryonic fibroblasts were implanted into the hydrogel scaffold, and the cell proliferation and myogenic transdifferentiation were conducted in 3D to produce the whole-cut meat mimics. Compared to 2D, cells grown in 3D matrix showed elevated myogenesis and collagen production. We further induced fat deposition in the transdifferentiated muscle cells and the triglyceride content could be manipulated to match and exceed the levels of chicken meat. The gene expression analysis indicated that both lineage-specific and multifunctional signalings could contribute to the generation of muscle/fat matrix. Overall, we were able to precisely modulate muscle, fat, and extracellular matrix contents according to balanced or specialized meat preferences. These findings provide new avenues for customized cultured meat production with desired intramuscular fat contents that can be tailored to meet the diverse demands of consumers.

Beyond the Books: COVID-19's Influence on Future Life Behaviors of Aspiring Medical and Health Professionals.

BACKGROUND: The lifestyle of most people was forced to change due to the COVID-19 pandemic. Perhaps after the pandemic, we will find that these subtle changes in life and from the depths of our hearts are thorough and profound. They may form our conceptual consensus and behavioral habits, becoming part of our long-term personal consciousness. This study explored the impacts of the COVID-19 pandemic on the future life behavior intentions of medical and health-related students studying at universities in China. METHODS: Electronic questionnaires were distributed to students studying at 3 universities in China. A total of 251 valid questionnaires were obtained, and the chi-squared test was used to compare the corresponding groups. RESULTS: In the future, students plan to pay more attention to wearing masks and maintaining social distance in public places, do more online shopping, have more meals at home or in the canteen, engage in less international travel, and have fewer gatherings with friends. However, compared with Chinese students, more non-Chinese students plan to increase domestic and international travel and reduce online learning. Furthermore, only among non-Chinese students did gender, urban or rural origin, and family economic conditions influence how the COVID-19 pandemic affected their future life behaviors. CONCLUSION: The COVID-19 pandemic changed the future life behavior intentions of medical and health-related students. The future behaviors of these students will impact the entire society. This study will help the government and policymakers predict and prepare for general lifestyle changes in our society.

Acoustofluidic precise manipulation: Recent advances in applications for micro/nano bioparticles.

Acoustofluidic technologies that integrate acoustic waves and microfluidic chips have been widely used in bioparticle manipulation. As a representative technology, acoustic tweezers have attracted significant attention due to their simple manufacturing, contact-free operation, and low energy consumption. Recently, acoustic tweezers have enabled the efficient and smart manipulation of biotargets with sizes covering millimeters (such as zebrafish) and nanometers (such as DNA). In addition to acoustic tweezers, other related acoustofluidic chips including acoustic separating, mixing, enriching, and transporting chips, have also emerged to be powerful platforms to manipulate micro/nano bioparticles (cells in blood, extracellular vesicles, liposomes, and so on). Accordingly, some interesting applications were also developed, such as smart sensing. In this review, we firstly introduce the principles of acoustic tweezers and various related technologies. Second, we compare and summarize recent applications of acoustofluidics in bioparticle manipulation and sensing. Finally, we outlook the future development direction from the perspectives such as device design and interdisciplinary.

Microwave-Enabled Fast Preparation of a Metal-Organic Framework Hybrid Membrane for Filtration-Enhanced Simultaneous Separation and Detection of Aflatoxin B1.

Mycotoxin contamination in food and the environment seriously harms human health. Sensitive and timely detection of mycotoxins is crucial. Here, we report a dual-functional hybrid membrane with absorptivity and responsiveness for fluorescent-quantitative detection of mycotoxin aflatoxin B1 (AFB1). A biomineralization-inspired and microwave-accelerated fabrication method was established to prepare a hybrid membrane with a metal-organic framework (MOF) loaded in high density. The MOF presented high efficiency in capturing AFB1 and showed fluorescence intensity alteration simultaneously, enabling a dual adsorption-response mode. Deriving from the inherent porous structure of the hybrid membrane and the absorptive/responsive ability of the loaded MOF, a filtration-enhanced detection mode was elaborated to provide a 1.67-fold signal increase compared with the conventional soaking method. Therefore, the hybrid membrane exhibited a rapid response time of 10 min and a low detection limit of 0.757 ng mL-1, superior to most analogues in rapidity and sensitivity. The hybrid membrane also presented superior specificity, reproducibility, and anti-interference ability and even performed well in extreme environments such as strong acid or alkaline, satisfying the practical requirements for facile and in-field detection. Therefore, the membrane had strong applicability in chicken feed samples, with a detection recovery between 70.6% and 101%. The hybrid membrane should have significant prospects in the rapid and in-field inspection of mycotoxins for agriculture and food.

Melatonin attenuates sepsis-induced acute kidney injury by promoting mitophagy through SIRT3-mediated TFAM deacetylation.

ABBREVIATIONS: AKI: acute kidney injury; ATP: adenosine triphosphate; BUN: blood urea nitrogen; CLP: cecal ligation and puncture; eGFR: estimated glomerular filtration rate; H&E: hematoxylin and eosin staining; LCN2/NGAL: lipocalin 2; LPS: lipopolysaccharide; LTL: lotus tetragonolobus lectin; mKeima: mitochondria-targeted Keima; mtDNA: mitochondrial DNA; PAS: periodic acid - Schiff staining; RTECs: renal tubular epithelial cells; SAKI: sepsis-induced acute kidney injury; Scr: serum creatinine; SIRT3: sirtuin 3; TFAM: transcription factor A, mitochondrial; TMRE: tetramethylrhodamine.

Regulatory networks of circRNA- centred ceRNAs in sepsis-induced acute kidney injury.

Sepsis is the primary cause of acute kidney injury (AKI) and is associated with high mortality rates. Growing evidence suggests that noncoding RNAs are vitally involved in kidney illnesses, whereas the role of circular RNAs (circRNAs) in sepsis-induced AKI (SAKI) remains largely unknown. In this present study, caecal ligation and puncture (CLP) in mice was performed to establish an SAKI model. The expression of circRNAs and mRNAs was analysed using circRNA microarray or next-generation sequencing. The results revealed that the expressions of 197 circRNAs and 2509 mRNAs were dysregulated. Validation of the selected circRNAs was performed by qRT-PCR. Bioinformatics analyses and chromatin immunoprecipitation demonstrated that NF-κB/p65 signalling induced the upregulation of circC3, circZbtb16, and circFkbp5 and their linear counterparts by p65 transcription in mouse tubular epithelial cells (mTECs). Furthermore, competitive endogenous RNA (ceRNA) networks demonstrated that some components of NF-κB signalling were potential targets of these dysregulated circRNAs. Among them, Tnf-α was increased by circFkbp5 through the downregulation of miR-760-3p in lipopolysaccharide (LPS)-stimulated mTECs. Knocking down circFkbp5 inhibited the p65 phosphorylation and apoptosis in injured mTECs. These findings suggest that the selected circRNAs and the related ceRNA networks provide new knowledge into the fundamental mechanism of SAKI and circFkbp5/miR-760-3p/Tnf-α axis might be therapeutic targets.

Construction of Multifunctional Hierarchical Biofilms for Highly Sensitive and Weather-Resistant Fire Warning.

Multifunctional biofilms with early fire-warning capabilities are highly necessary for various indoor and outdoor applications, but a rational design of intelligent fire alarm films with strong weather resistance remains a major challenge. Herein, a multiscale hierarchical biofilm based on lignocellulose nanofibrils (LCNFs), carbon nanotubes (CNTs) and TiO2 was developed through a vacuum-assisted alternate self-assembly and dipping method. Then, an early fire-warning system that changes from an insulating state to a conductive one was designed, relying on the rapid carbonization of LCNFs together with the unique electronic excitation characteristics of TiO2. Typically, the L-CNT-TiO2 film exhibited an ultrasensitive fire-response signal of ~0.30 s and a long-term warning time of ~1238 s when a fire disaster was about to occur, demonstrating a reliable fire-alarm performance and promising flame-resistance ability. More importantly, the L-CNT-TiO2 biofilm also possessed a water contact angle (WCA) of 166 ± 1° and an ultraviolet protection factor (UPF) as high as 2000, resulting in excellent superhydrophobicity, antifouling, self-cleaning as well as incredible anti-ultraviolet (UV) capabilities. This work offers an innovative strategy for developing advanced intelligent films for fire safety and prevention applications, which holds great promise for the field of building materials.

Mechanochemical Rhodium-Catalyzed C-H Bond Amidation of Ferrocenes by Ball Milling.

A direct protocol for Rh-catalyzed C-H amidation of ferrocenes in a ball mill using dioxazolones as the amide source under solvent-free conditions was developed. The corresponding ortho-aminated products were formed in 3 hours and the yields were up to 99% in the absence of base. This method could be a typically sustainable and environmental-friendly alternative method to traditional methodologies, with the advantages of wide substrate range, good functional group tolerance and gram-scale synthesis.

[PDS5B inhibits the proliferation of A549 human lung cancer cells via downregulation of Wnt5a].

Objective To investigate the effect of PDS5B on the biological function of A549 human lung cancer cells and possible molecular mechanism. Methods The proliferation of lung cancer cells was detected by MTT assay and colony formation assay after silencing or overexpressing PDS5B of A549 cells. The cell migration was detected by scratch assay and TranswellTM assay. The protein expression of PDS5B and Wnt5a in A549 cells was detected by Western blot analysis. Cell migration was detected by TranswellTM after PDS5B small interference RNA(siRNA) and Wnt5a siRNA were co-transfected. Results Compared with the negative control group, the protein expression of PDS5B decreased significantly after transfected with PDS5B siRNA. The proliferation ability , colony formation rate and migration ability of A549 cells significantly improved, and the expression of Wnt5a was increased. The opposite results were observed after PDS5B over-expression. The co-transfer experiment showed that Wnt5a could resist the inhibition of A549 cells by PDS5B. Conclusion PDS5B inhibits lung cancer cell proliferation by down-regulating Wnt5a expression.

Metal-Organic Framework-Decorated Nanochannel Electrode: Integration of Internal Nanoconfined Space and Outer Surface for Small-Molecule Sensing.

Ionic current measurement has been the dominant signaling strategy in nanochannel-based sensors. However, the direct probing of the capture of small molecules is still challenging, and the sensing potential of the outer surface of nanochannels is always ignored. Here, we report the fabrication of an integrated nanochannel electrode (INCE) with nanoporous gold layers modified on two sides of nanochannels, and its application for small-molecule analysis was explored. Metal-organic frameworks (MOFs) were decorated inside and outside of nanochannels, enabling the reduction of pore size to several nanometers, which is among the thickness range of the electric double layer for confined ion diffusion. Combined with excellent adsorption characteristics of MOFs, the developed nanochannel sensor successfully constructed the internal nanoconfined space that could directly capture small molecules and instantly generate a current signal. The contribution of the outer surface and the internal nanoconfined space to diffusion suppression to electrochemical probes was investigated. We found that the constructed nanoelectrochemical cell was sensitive in both the inner channel and the outer surface, signifying a novel sensing mode with integration of the internal nanoconfined space and the outer surface of nanochannels. The MOF/INCE sensor showed excellent performance toward tetracycline (TC) with a detection limit of 0.1 ng·mL-1. Subsequently, sensitive and quantitative detection of TC down to 0.5 µg·kg-1 was achieved in actual chicken samples. This work may open up a new model of nanoelectrochemistry and provide an alternative solution in the field of nanopore analysis for small molecules.

Recent advances in determination applications of emerging films based on nanomaterials.

Sensitive and facile detection of analytes is crucial in various fields such as agriculture production, food safety, clinical diagnosis and therapy, and environmental monitoring. However, the synergy of complicated sample pretreatment and detection is an urgent challenge. By integrating the inherent porosity, processability and flexibility of films and the diversified merits of nanomaterials, nanomaterial-based films have evolved as preferred candidates to meet the above challenge. Recent years have witnessed the flourishment of films-based detection technologies due to their unique porous structures and integrated physical/chemical merits, which favors the separation/collection and detection of analytes in a rapid, efficient and facile way. In particular, films based on nanomaterials consisting of 0D metal-organic framework particles, 1D nanofibers and carbon nanotubes, and 2D graphene and analogs have drawn increasing attention due to incorporating new properties from nanomaterials. This paper summarizes the progress of the fabrication of emerging films based on nanomaterials and their detection applications in recent five years, focusing on typical electrochemical and optical methods. Some new interesting applications, such as point-of-care testing, wearable devices and detection chips, are proposed and emphasized. This review will provide insights into the integration and processability of films based on nanomaterials, thus stimulate further contributions towards films based on nanomaterials for high-performance analytical-chemistry-related applications.