Effectiveness of traditional chinese medicine (TCM) exercise therapy intervention on the cognitive function in the elderly: A systematic review and meta-analysis.

OBJECTIVES: There exists a deficiency in a distinct understanding of the intervention effects of Traditional Chinese Medicine (TCM) exercise therapies (Tai Chi, Yi Jin Jing, Ba Duan Jin, Liu Zi Jue, Qigong, Wu Qin Xi etc.) on cognitive function and its moderating variables in the elderly. This study aims to systematically evaluate the effects of TCM exercise therapies on the cognitive function of the elderly and further propose the best exercise intervention programme to delay the cognitive decline of the elderly. METHODS: PubMed, EBSCO host, Web of Science, EMbase, China National Knowledge Infrastructure and Wan Fang databases were searched for the effects of TCM exercise therapies on the cognitive function in older adults until July 2022. A meta-analysis of the included literature was performed using Stata 12.0 software, with a subgroup analysis of seven moderating variables: subject type, intervention content, intervention duration, intervention frequency, intervention period, study type and sample size. A random effects model was used to combine the overall effect sizes and to test for heterogeneity and publication bias across studies. RESULTS: A total of 20 publications with 1975 subjects were included. The TCM exercise therapies delayed cognitive decline in older adults (d = 0.83; 95 % CI [0.62-1.04]; P < 0.001). Subgroup analysis found that intervention content, intervention duration, intervention frequency, and intervention period were significant moderating variables influencing the effectiveness of the intervention. Among them, the Ba Duan Jin intervention (d = 0.85; 95 % CI [0.65-1.06]; P < 0.001), the duration of each exercise session of 60 min or more (d = 0.86; 95 % CI [0.71-1.00]; P < 0.001), the frequency of exercise of more than 5 times per week (d = 0.80; 95 % CI [0.64-0.96]; P < 0.001) and exercise cycles of 6-9 months (d = 0.96; 95 % CI [0.80-1.12]; P < 0.001) produced the largest effect sizes. CONCLUSION: TCM exercise therapies can effectively improve the cognitive function of the elderly. The best effect on the cognitive function of the elderly was achieved by choosing Ba Duan Jin and exercising at least five times a week for at least 60 min each time for a total of 6-9 months. The effect size of the TCM exercise therapy interventions on the cognitive function in older adults may be overestimated because of publication bias. In addition, large-sample, multicenter, high-quality randomised controlled trials should be conducted to validate this result.

Afterglow/Fluorescence Dual-Emissive Ratiometric Oxygen Probe for Tumor Hypoxia Imaging.

Hypoxia is a common feature of many diseases such as solid tumors. The measurement and imaging of oxygen (O2) are extremely important for disease diagnosis and therapy evaluation. In this work, the afterglow/fluorescence dual-emissive ratiometric O2 probe based on a photochemical reaction-based afterglow system is reported. The afterglow is highly sensitive to O2 because the O2 content is directly related to the 1O2 yield and eventually affects the afterglow intensity. The O2-insensitive fluorescence of an emitter can serve as an internal reference. As the O2 concentration changes from 0.08 to 18.5 mg L-1, the ratio value shows a remarkable 53-fold increase. Compared with the intensity of a single peak, the ratiometric signal can eliminate the interference of the probe concentration to achieve higher accuracy. This afterglow/fluorescence dual-emissive ratiometric O2 probe is successfully applied to hypoxia imaging in tumor-bearing mice, which may further promote the development of O2 sensing in the biomedical field.

Modulating Triplet Excited States of Organic Semiconductors via Tuning Molecular Conformation for Dual-ratiometric Thermometers.

The dual-ratiometric thermometry is one of highly accurate methods for microscopic thermal measurement in biological systems. Herein, a series of chromone derivatives with noncovalently intramolecular interactions (NIIs) were designed and synthesized for ratiometric thermometers. The triplet states of these organic compounds were systematically tuned upon regulating the conformation with NIIs to yield efficient room temperature phosphorescence and large wavelength difference between fluorescence and phosphorescence simultaneously. As a result, an unprecedent organic 3D dual-ratiometric thermometer was established based on the intensity ratio and lifetime ratio of fluorescence/phosphorescence vs temperature, which was used for in vitro and in vivo bio-thermometry with high accuracy. This work provides a novel method to achieve organic dual ratiometric thermometers via tuning the triplet excited states.

Ultra-long Near-infrared Repeatable Photochemical Afterglow Mediated by Reversible Storage of Singlet Oxygen for Information Encryption.

Photochemical afterglow systems have drawn considerable attention in recent years due to their regulable photophysical properties and charming application potential. However, conventional photochemical afterglow suffered from its unrepeatability due to the consumption of energy cache units as afterglow photons are emitted. Here we report a novel strategy to realize repeatable photochemical afterglow (RPA) through the reversible storage of 1 O2 by 2-pyridones. Near-infrared afterglow with a lifetime over 10 s is achieved, and its initial intensity shows no significant reduction over 50 excitation cycles. A detailed mechanism study was conducted and confirmed the RPA is realized through the singlet oxygen-sensitized fluorescence emission. Furthermore, the generality of this strategy is demonstrated and tunable afterglow lifetimes and colors are achieved by rational design. The developed RPA is further applied for attacker-misleading information encryption, presenting a repeatable-readout.

Er-Based Luminescent Nanothermometer to Explore the Real-Time Temperature of Cells under External Stimuli.

Temperature as a typical parameter, which influences the status of living creatures, is essential to life activities and indicates the initial cellular activities. In recent years, the rapid development of nanotechnology provides a new tool for studying temperature variation at the micro- or nano-scales. In this study, an important phenomenon is observed at the cell level using luminescent probes to explore intracellular temperature changes, based on Yb-Er doping nanoparticles with special upconversion readout mode and intensity ratio signals (I525 and I545 ). Further optimization of this four-layer core-shell ratio nanothermometer endows it with remarkable characteristics: super photostability, sensitivity, and protection owing to the shell. Thus this kind of thermal probe has the property of anti-interference to the complex chemical environment, responding exclusively to temperature, when it is used in liquid and cells to reflect external temperature changes at the nanoscale. The intracellular temperature of living RAW and CAOV3 cells are observed to have a resistance mechanism to external stimuli and approach a more favorable temperature, especially for CAOV3 cells with good heat resistance, with the intracellular temperature 4.8 °C higher than incubated medium under 5 °C environment, and 4.4 °C lower than the medium under 60 °C environment.

Afterglow Implant for Arterial Embolization and Intraoperative Imaging.

Transcatheter arterial embolization (TAE) is wildly used in clinical treatments. However, the online monitoring of the thrombosis formation is limited due to the challenges of the direct visualization of embolic agents and the real-time monitoring of dynamic blood flow. Thus, we developed a photochemical afterglow implant with strong afterglow intensity and a long lifetime for embolization and imaging. The liquid pre-implant injected into the abdominal aorta of mice was rapidly transformed into a hydrogel in situ to embolize the blood vessel. The vascular embolism position can be observed by the enhanced afterglow of the fixed implant, and the long lifetime of afterglow can also be used to monitor the effect of embolization. This provides an excellent candidate in bio-imaging to avoid the autofluorescence interference from continuous light excitation. The study suggests the potential usefulness of the implant as an embolic agent in TAE and artery imaging during a surgical procedure.

Enhanced Blue Afterglow through Molecular Fusion for Bio-applications.

Afterglow materials have drawn considerable attention due to their attractive luminescent properties. However, their low-efficiency luminescence in aqueous environment limits their applications in life sciences. Here, we developed a molecular fusion strategy to improve the afterglow efficiency of photochemical afterglow materials. By fusing a cache unit with an emitter, we obtained a blue afterglow system with a quantum yield up to 2.59 %. This is 162 times higher than that achieved with the traditional physical mixing system and more than an order of magnitude larger than that of the covalent coupling system. High-efficiency afterglow nanoparticles were obtained and utilized for bio-imaging with a high signal-to-noise ratio (SNR) of 131, and for the lateral flow immunoassay (LFIA) of ß-hCG with a low limit of detection (LOD) of 0.34 mIU mL-1 . This paves a new way for the construction of high-efficiency afterglow materials and expands the number of luminescence reporter candidates for disease diagnosis and bio-imaging.

A Universal Photoactivatable Tag Attached to Fluorophores Enables Their Use for Single-Molecule Imaging.

Single molecule localization microscopy based on photoactivation is a powerful tool for investigating the ultrastructure of cells. We developed a general strategy for photoactivatable fluorophores, using 2,3-dihydro-1,4-oxathiine group (SO) as a tag to attach to various skeletal structures, including coumarin, BODIPY, rhodamine, and cyanine. The conjugation of SO resulted in a significant loss of fluorescence due to photoinduced electron transfer (PeT). Under the irradiation of excitation light, singlet oxygen generated by the fluorophores converted the SO moiety into its ester derivative, terminated the PeT process, and restored the fluorescence. Single molecule localization imaging was achieved using a dual functional illuminating beam in the visible, acting as both the activating and the exciting source. We successfully applied these photoactivatable probes for time-lapse super-resolution tracking in living cells and super-resolution imaging of microtubule structures in neurons.

Two-Photon Excitation-Based Imaging Postprocessing Algorithm Model for Background-Free Bioimaging.

Bioimaging is a powerful strategy for studying biological activities, which is still limited by the difficulty of distinguishing obscured signals from high background. Despite the development of various new imaging materials and methods, target signals are still likely to be submerged in spontaneous fluorescence or scattering signals. Herein, a novel two-photon excitation-process-based imaging postprocessing algorithm model (2PIA) is introduced to minimize background noise, and triplet-triplet annihilation upconversion metal-organic frameworks (UCMOFs) are chosen as demonstration. Through the collection of several image stacks, the related polynomial of the luminescence intensity and excitation power was established, following splitting the desired signals from noise and obtaining the background-free images definitely. Both in vitro and in vivo experiments show that improved signal visibility is achieved through 2PIA and UCMOFs by removing the interference of scattering, bioluminescence, and other fluorescence materials. The imaging spatial resolution and tissue penetration depth were greatly enhanced. Benefiting from 2PIA, as low as 100 UCMOFs labeled cells can be identified from obscuring background easily after intravenous injection. This image postprocessing method combined with special two-photon excited luminescent materials can conduct biological imaging from complex background interference without using expensive instruments or delicate materials, which holds great promise for accurate biological imaging.

Light-Responsive Luminescent Materials for Information Encryption Against Burst Force Attack.

Optical encryption with easy operation, multichannel and high security has been one of the most significant technologies for information security. Stimuli-responsive luminescent materials have emerged as an ideal candidate for optical encryption, owing to its smart responsive property and high security. Herein, a type of light-responsive multicolor luminescent materials for high-security information encryption, which are fabricated by combining sensitizer, consumption unit, and emitter is developed. Different types of sensitizers to achieve different stimulus light responses, and multicolor light-responsive luminescent can be obtained by varying the composition of perovskite nanocrystals emitter can be selected. Both stimulus light and emission color can be used as distinguishable encoding dimensions, which enable multiplexed encoding with high capacity and complexity. Importantly, the controllable consumption can be manipulated by varying the concentration of consumption unit, so the programmed information encoded in different channels can be selectively read and erased simultaneously by varying stimulus light. The method makes the encryption information highly resistive to brute force trial-and-error attacks, which achieves high security level of information protection.

Yb-Based Nanoparticles with the Same Excitation and Emission Wavelength for Sensitive in Vivo Biodetection.

Near-infrared luminescent emission has been widely used as a signal for biological detection with its high spatial resolution and fast response. Rare-earthdoped nanoparticle-dye composites have diverse advantages of a wide operation wavelength and remarkable light stability, while the application is limited by the low luminescence quantum yield of rare-earth nanoparticles. Hence, in this work, we use a singly Yb doped nanoparticle that has strong luminescence emission at 975 nm under excitation at the same wavelength as an energy donor to construct the detection system. An inner filter pair, composed of core-shell nanophosphor NaYF4/20%Yb@NaYF4 (1:2) nanocrystals (csYb) as a luminescent beacon and ClO--responsive cyanine dye Cy890 as a filtering agent, was designed as a model. With a time-gated detection mode, the nanocomposites realize the detection limit at 0.55 ppb as demonstrated in a ClO- detection trial. The csYb&Cy890 nanocomposites can also monitor ClO- by luminescence signals in both living cells and mice models.

Metabolic Labeling of Peptidoglycan with NIR-II Dye Enables In Vivo Imaging of Gut Microbiota.

Deepening our understanding of mammalian gut microbiota has been greatly hampered by the lack of a facile, real-time, and in vivo bacterial imaging method. To address this unmet need in microbial visualization, we herein report the development of a second near-infrared (NIR-II)-based method for in vivo imaging of gut bacteria. Using d-propargylglycine in gavage and then click reaction with an azide-containing NIR-II dye, gut microbiota of a donor mouse was strongly labeled with NIR-II fluorescence on their peptidoglycan. The bacteria could be readily visualized in recipient mouse gut with high spatial resolution and deep tissue penetration under NIR irradiation. The NIR-II-based metabolic labeling strategy reported herein, provides, to the best of our knowledge, the first protocol for facile in vivo visualization of gut microbiota within deep tissues, and offers an instrumental tool for deciphering the complex biology of these gut "dark matters".

Luminescence Lifetime-Based In Vivo Detection with Responsive Rare Earth-Dye Nanocomposite.

For years, luminescence lifetime imaging has served as a quantitative tool in indicating intracellular components and activities. However, very few studies involve the in vivo study of animals, especially in vivo stimuli-responsive activities of animals, as both excitation and emission wavelengths should fall into the near-infrared (NIR) optical transparent window (660-950 and 1000-1500 nm). Herein, this work reports a lifetime-responsive nanocomposite with both excitation and emission in the NIR I window (800 nm) and lifetime in the microsecond region. The incorporation of Tm3+ -doped rare-earth nanocrystals and NIR dye builds an efficient energy transfer pathway that enables a tunable luminescence lifetime range. The NaYF4 :Tm nanocrystal, which absorbs and emits photons at the same energy level, is found to be 33 times brighter than optimized core-shell upconversion nanocrystals, and proved to be an effective donor for NIR luminescence resonance energy transfer (LRET). The anti-interference capability of luminescence lifetime signals is further confirmed by luminescence and lifetime imaging. In vivo studies also verify the lifetime response upon stimulation generated in an arthritis mouse model. This work introduces an intriguing tool for luminescence lifetime-based sensing in the microsecond region.

Lanthanide-Doped Nanoparticles with Upconversion and Downshifting Near-Infrared Luminescence for Bioimaging.

We designed and synthesized NaYF4:Yb,Tm@LiLuF4:Nd core-shell nanoparticles, which can emit at ∼800 nm under 980 nm excitation and at ∼1060 nm under 808 nm excitation, simultaneously having an upconversion and downshifting mechanism for near-infrared (NIR) emission. After surface modification with sodium citrate, the soluble nanoparticles were used in the in vitro NIR luminescence imaging to compare the penetration depth and the scattering of tissue. Furthermore, to determine the differences between the upconversion and downshifting fluorescence for biological imaging, the soluble nanoparticles also were operated on the aforementioned two modes for in vivo imaging.

Tuning the Upconversion Efficiency and Spectrum of Upconversion Nanoparticles through Surface Decorating of an Organic Dye.

In this paper, we utilized the energy-transfer process between upconversion nanoparticles (UCNPs) and organic dye molecules to enhance the upconversion quantum yield (UCQY) of a UCNPs-dye system and tune the luminescence output color. The results indicate that adding an energy dissipation pathway to the energy donor through an energy-transfer process can decrease the ratio of nonradiative transition and cause a new radiative pathway. Through calculation of the rate equations, we studied the effects of the energy-transfer efficiency and activator type on the UCQY enhancement. On the basis of calculations of the CIE color coordinates, tunable color from Er3+, Tm3+, Ho3+, and Tb3+ ions was generated by surface decorating of an organic dye. The approach described here provides a new way to optimize the UCQY and manipulate the emission through energy transfer in a nanoscopic region.

Thuricin†Z: A Narrow-Spectrum Sactibiotic that Targets the Cell Membrane.

Sactionine-containing antibiotics (sactibiotics) are a growing class of peptide antibiotics belonging to the ribosomally synthesized and post-translationally modified peptide (RiPP) superfamily. We report the characterization of thuricin Z, a novel sactibiotic from Bacillus thuringiensis. Unusually, the biosynthesis of thuricin Z involves two radical S-adenosylmethionine (SAM) enzymes, ThzC and ThzD. Although ThzC and ThzD are highly divergent from each other, these two enzymes produced the same sactionine ring in the precursor peptide ThzA in vitro. Thuricin Z exhibits narrow-spectrum antibacterial activity against Bacillus cereus. A series of analyses, including confocal laser scanning microscopy, ultrathin-sectioning transmission electron microscopy, scanning electron microscopy, and large-unilamellar-vesicle-based fluorescence analysis, suggested that thuricin Z binds to the bacterial cell membrane and leads to membrane permeabilization.

3D Long-Range Triplet Migration in a Water-Stable Metal-Organic Framework for Upconversion-Based Ultralow-Power in Vivo Imaging.

Triplet-triplet annihilation upconversion (TTA-UC) has gained increasing attention because it allows for harvesting of low-energy photons in the solar spectrum with high efficiency in relevant applications including solar cells and bioimaging. However, the utilization of conventional TTA-UC systems for low-power bioapplications is significantly hampered by their general incompatibility and low efficiency in aqueous media. Herein we report a metal-organic framework (MOF) as a biocompatible nanoplatform for TTA-UC to realize low-power in vivo imaging. Our MOF consists of a porphyrinic sensitizer in an anthracene-based Zr-MOF as a TTA-UC platform. In particular, closely aligned chromophores in the MOF facilitate a long-range 3D triplet diffusion of 1.6 µm allowing efficient energy migration in water. The tunable ratio between sensitizer and annihilator by our synthetic method also allows an optimization of the system for maximized TTA-UC efficiency in water at a very low excitation power density. Consequently, the low-power imaging of lymph node in a live mouse was successfully demonstrated with an excellent signal-to-noise ratio (SNR > 30 at 5 mW cm-2).

Resonance Energy Transfer in Upconversion Nanoplatforms for Selective Biodetection.

Resonance energy transfer (RET) describes the process that energy is transferred from an excited donor to an acceptor molecule, leading to a reduction in the fluorescence emission intensity of the donor and an increase in that of the acceptor. By this technique, measurements with the good sensitivity can be made about distance within 1 to 10 nm under physiological conditions. For this reason, the RET technique has been widely used in polymer science, biochemistry, and structural biology. Recently, a number of RET systems incorporated with nanoparticles, such as quantum dots, gold nanoparticles, and upconversion nanoparticles, have been developed. These nanocrystals retain their optical superiority and can act as either a donor or a quencher, thereby enhancing the performance of RET systems and providing more opportunities in excitation wavelength selection. Notably, lanthanide-doped upconversion nanophosphors (UCNPs) have attracted considerable attention due to their inherent advantages of large anti-Stoke shifts, long luminescence lifetimes, and absence of autofluorescence under low energy near-infrared (NIR) light excitation. These nanoparticles are promising for the biodetection of various types of analytes. Undoubtedly, the developments of those applications usually rely on resonance energy transfer, which could be regarded as a flexible technology to mediate energy transfer from upconversion phosphor to acceptor for the design of luminescent functional nanoplatforms. Currently, researchers have developed many RET-based upconversion nanosystems (RET-UCNP) that respond to specific changes in the biological environments. Specifically, small organic molecules, biological molecules, metal-organic complexes, or inorganic nanoparticles were carefully selected and bound to the surface of upconversion nanoparticles for the preparation of RET-UCNP nanosystems. Benefiting from the advantage and versatility offered by this technology, the research of RET-based upconversion nanomaterials should have significant implications for advanced biomedical applications. It should be noted that energy transfer in a UCNP based nanosystem is most often related to resonance energy transfer but that reabsorption (and maybe other energy transfer processes) may also play an important role and that more studies regarding the fundamental aspects for energy transfer with UCNPs is necessary. In this Account, we present an overview of recent advances in RET-based upconversion nanocomposites for biodetection with a particular focus on our own work. We have designed a series of upconversion nanoplatforms with remarkably high versatility for different applications. The experience gained from our strategic design and experimental investigations will allow for the construction of next-generation luminescent nanoplatform with marked improvements in their performance. The key aspects of this Account include fundamental principles, design and preparation strategies, biodetection in vitro and in vivo, future opportunities, and challenges of RET-UCNP nanosystems.

Dual functional NaYF4:Yb3+, Er3+@NaYF4:Yb3+, Nd3+ core-shell nanoparticles for cell temperature sensing and imaging.

Lanthanide-doped up-conversion nanoparticles (UCNPs) provide a remote temperature sensing approach to monitoring biological microenvironments. In this research, the UCNPs of NaYF4:Yb3+, Er3+@NaYF4:Yb3+, Nd3+ with hexagonal (ß)-phase were synthesized and applied in cell temperature sensing as well as imaging after surface modification with meso-2, 3-dimercaptosuccinic acid. In the core-shell UCNPs, Yb3+ ions were introduced as energy transfer media between sensitizers of Nd3+ and activators of Er3+ to improve Er3+emission and prevent their quenching behavior due to multiple energy levels of Nd3+. Under the excitations of 808 nm and 980 nm lasers, the NaYF4:Yb3+, Er3+@NaYF4:Yb3+, Nd3+ nanoparticles exhibited an efficient green band with two emission peaks at 525 nm and 545 nm, respectively, which originated from the transitions of 2H11/2 â†’ 4I15/2 and 4S3/2 â†’ 4I15/2 for Er3+ ions. We demonstrate that an occurrence of good logarithmic linearity exists between the intensity ratio of these two emission peaks and the reciprocal of the inside or outside temperature of NIH-3T3 cells. A better thermal stability is proved through temperature-dependent spectra with a heating-cooling cycle. The obtained viability of NIH-3T3 cells is greater than 90% after incubations of about 12 and 24 (h), and they possess a lower cytotoxicity of UCNPs. This work provides a method for monitoring the cell temperature and its living state from multiple dimensions including temperature response, cell images and visual up-conversion fluorescent color.

Anti-Stokes shift luminescent materials for bio-applications.

Anti-Stokes shift luminescence is a special optical process, which converts long-wavelength excitation to short-wavelength emission. This unique ability is especially helpful for bio-applications, because the longer-wavelength light source, usually referring to near infrared light, has a larger penetration depth offering a longer working distance for in vivo applications. The anti-Stokes shift luminescence signal can also be distinguished from the auto-fluorescence of biological tissues, thus reducing background interference during bioimaging. Herein, we summarize recent advances in anti-Stokes shift luminescent materials, including lanthanide and triplet-triplet-annihilation-based upconversion nanomaterials, and newly improved hot-band absorption-based luminescent materials. We focus on the synthetic strategies, optical optimization and biological applications as well as present comparative discussions on the luminescence mechanisms and characteristics of these three types of luminescent materials.