Table_1_Care burden on family caregivers of patients with dementia and affecting factors in China: A systematic review.DOCX

BackgroundDementia is a chronic and progressive illness characterized by severe impairment and high dependencies. Under the influence of Chinese traditional culture, 80% of patients with dementia are watched over at home by family caregivers as primary caregivers. However, long-term care brings formidable burdens to them and reduces the quality of their life. It is necessary to find out the influencing factors of caregivers’ burden.MethodsA scoping search was conducted on eight electronic databases from 1 January 2010 to 14 June 2022: PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, China VIP Database, China Biomedical Literature Database, and Wanfang Data Knowledge Service Platform. Research articles included in this review discussed the factors affecting Chinese dementia family caregivers’ care burden or stress, and the level of care burden was evaluated by a standardized care burden scale.ResultsA total of 1,888 related articles were found and 23 cross-sectional studies were eventually included. After quality assessment, 12 were of good quality and 11 were of fair quality. A total of 32 factors were identified that were associated with caregiver burden, and the results were grouped into three categories: patient, caregiver, and society. The severity of disease, poor self-care ability, neuropsychiatric symptoms, care time, number of helpers, poor health status, economic stress, poor psychological status, social support, and age were reported in many previous studies.ConclusionIn this review, the factors that affect the caregiver burden for people with dementia were clarified. By identifying these factors, hospitals, decision-makers, and communities can carry out special projects for these populations, provide appropriate assistance, or design corresponding intervention measures to reduce the caregiver burden and improve the quality of care for patients with dementia.Systematic review registration[https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42022347816].</p

Table_2_Care burden on family caregivers of patients with dementia and affecting factors in China: A systematic review.docx

BackgroundDementia is a chronic and progressive illness characterized by severe impairment and high dependencies. Under the influence of Chinese traditional culture, 80% of patients with dementia are watched over at home by family caregivers as primary caregivers. However, long-term care brings formidable burdens to them and reduces the quality of their life. It is necessary to find out the influencing factors of caregivers’ burden.MethodsA scoping search was conducted on eight electronic databases from 1 January 2010 to 14 June 2022: PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, China VIP Database, China Biomedical Literature Database, and Wanfang Data Knowledge Service Platform. Research articles included in this review discussed the factors affecting Chinese dementia family caregivers’ care burden or stress, and the level of care burden was evaluated by a standardized care burden scale.ResultsA total of 1,888 related articles were found and 23 cross-sectional studies were eventually included. After quality assessment, 12 were of good quality and 11 were of fair quality. A total of 32 factors were identified that were associated with caregiver burden, and the results were grouped into three categories: patient, caregiver, and society. The severity of disease, poor self-care ability, neuropsychiatric symptoms, care time, number of helpers, poor health status, economic stress, poor psychological status, social support, and age were reported in many previous studies.ConclusionIn this review, the factors that affect the caregiver burden for people with dementia were clarified. By identifying these factors, hospitals, decision-makers, and communities can carry out special projects for these populations, provide appropriate assistance, or design corresponding intervention measures to reduce the caregiver burden and improve the quality of care for patients with dementia.Systematic review registration[https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42022347816].</p

Incorporation of Porphyrin to π‑Conjugated Backbone for Polymer-Dot-Sensitized Photodynamic Therapy

The photosensitizers used in photodynamic therapy are mainly based on porphyrin derivatives. However, clinical applications encounter several limitations regarding photosensitizers such as their low absorption coefficients, poor water-solubility, and leaching from delivery carriers. Here, we describe covalent incorporation of porphyrin in conjugated polymer backbone for development of efficient polymer-dot photosensitizer. Spectroscopic characterizations revealed that the light-harvesting polymer dominantly transfer the excitation energy to the porphyrin unit, yielding efficient singlet oxygen generation for photodynamic therapy. The polymer dots (Pdots) also possess excellent stability that overcomes the photosensitizer leaching problem as encountered in other nanoparticle carriers. In vitro cytotoxicity and photodynamic efficacy of the Pdots were evaluated in MCF-7 cells by in vitro assay, indicating that the Pdots can efficiently damage cancer cells. In vivo photodynamic therapy by using the Pdots was further investigated with xenograft tumors in Balb/c nude mice, which show that the tumors were significantly inhibited or eradicated in certain cases. The high-yield singlet oxygen generation and excellent stability of porphyrin-incorporated Pdots are promising for photodynamic treatment of malignant tumors

Near-Infrared II Semiconducting Polymer Dots: Chain Packing Modulation and High-Contrast Vascular Imaging in Deep Tissues

Fluorescence imaging in the second near-infrared (NIR-II) window has attracted considerable interest in investigations of vascular structure and angiogenesis, providing valuable information for the precise diagnosis of early stage diseases. However, it remains challenging to image small blood vessels in deep tissues because of the strong photon scattering and low fluorescence brightness of the fluorophores. Here, we describe our combined efforts in both fluorescent probe design and image algorithm development for high-contrast vascular imaging in deep turbid tissues such as mouse and rat brains with intact skull. First, we use a polymer blending strategy to modulate the chain packing behavior of the large, rigid, NIR-II semiconducting polymers to produce compact and bright polymer dots (Pdots), a prerequisite for in vivo fluorescence imaging of small blood vessels. We further developed a robust Hessian matrix method to enhance the image contrast of vascular structures, particularly the small and weakly fluorescent vessels. The enhanced vascular images obtained in whole-body mouse imaging exhibit more than an order of magnitude improvement in the signal-to-background ratio (SBR) as compared to the original images. Taking advantage of the bright Pdots and Hessian matrix method, we finally performed through-skull NIR-II fluorescence imaging and obtained a high-contrast cerebral vasculature in both mouse and rat models bearing brain tumors. This study in Pdot probe development and imaging algorithm enhancement provides a promising approach for NIR-II fluorescence vascular imaging of deep turbid tissues

Brightness Enhancement of Near-Infrared Semiconducting Polymer Dots for in Vivo Whole-Body Cell Tracking in Deep Organs

In vivo visualization of cell migration and engraftment in small animals provide crucial information in biomedical studies. Semiconducting polymer dots (Pdots) are emerging as superior probes for biological imaging. However, in vivo whole-body fluorescence imaging is largely constrained by the limited brightness of Pdots in near-infrared (NIR) region. Here, we describe the brightness enhancement of NIR fluorescent Pdots for in vivo whole-body cell tracking in deep organs. We first synthesize semiconducting polymers with strong absorption in orange and far-red regions. By molecular doping, the weak broad-band fluorescence of the Pdots was significantly narrowed and enhanced by 1 order of magnitude enhancement, yielding bright narrow-band NIR emission with a quantum yield of ∼0.21. Under an excitation of far-red light (676 nm), a trace amount of Pdots (∼2 μg) in the stomach can be clearly detected in whole-body fluorescence imaging of live mice. The Pdots coated with a cell-penetrating peptide are able to brightly label cancer cells with minimal cytotoxicity. In vivo cell tracking in live mice indicated that the entrapment and migration of the tail-vein-administered cells (∼400 000) were clearly visualized in real time. These Pdots with deep-red excitation and bright NIR emission are promising for in vivo whole-body fluorescence imaging

Site-Specific Modification of Single Domain Antibodies by Enzyme-Immobilized Magnetic Beads

Nanobodies as imaging agents and drug conjugates have shown great potential for cancer diagnostics and therapeutics. However, site-specific modification of a nanobody with microbial transglutaminase (mTGase) encounters problems in protein separation and purification. Here, we describe a facile yet reliable strategy of immobilizing mTGase onto magnetic beads for site-specific nanobody modification. The mTGase immobilized on magnetic beads (MB-mTGase) exhibits catalytic activity nearly equivalent to that of the free mTGase, with good reusability and universality. Magnetic separation simplifies the protein purification step and reduces the loss of nanobody bioconjugates more effectively than size exclusion chromatography. Using MB-mTGase, we demonstrate site-specific conjugation of nanobodies with fluorescent dyes and polyethylene glycol molecules, enabling targeted immunofluorescence imaging and improved circulation dynamics and tumor accumulation in vivo. The combined advantages of MB-mTGase method, including high conjugation efficiency, quick purification, less protein loss, and recycling use, are promising for site-specific nanobody functionalization and biomedical applications

Facile Synthesis, Macroscopic Separation, E/Z Isomerization, and Distinct AIE properties of Pure Stereoisomers of an Oxetane-Substituted Tetraphenylethene Luminogen

Control of stereochemistry plays a key role in medicinal chemistry, material and life science. As a prominent AIE luminogen, tetraphenylethene (TPE) derivatives have E/Z isomers which are challenging to separate even by HPLC. Herein, we designed oxetane-substituted TPE (TPE-2OXE) and separated pure isomers by simple column chromatography with high yields, as confirmed by mass spectrometry, IR and NMR spectroscopy. The isomerization of the two isomers can occur by photo- and thermo-activation. Importantly, (<i>Z</i>)-TPE-2OXE isomer solid shows bathochromic emission with a quantum yield 5 times higher than that of (<i>E</i>)-TPE-2OXE. The differences in emission wavelength and quantum yield are derived from distinct emission mechanisms of locally excited (LE) state emission of (<i>E</i>)-TPE-2OXE and charge transfer (CT) state emission of (<i>Z</i>)-TPE-2OXE. The two isomers are also good piezochromic luminescent materials, which have not only an obvious emission color shift but also significantly enhanced luminescence brightness by external force. In addition, (<i>E</i>)-TPE-2OXE solids show self-healing ability, which can crystallize spontaneously from ground amorphous state. The higher brightness of (<i>E</i>)-TPE-2OXE can be retained in solution, so fluorescent AIE nanodots are prepared from the two isomers. Cell-labeling experiments also show that (<i>Z</i>)-TPE-2OXE AIE dots have higher labeling brightness as compared to the (<i>E</i>)-TPE-2OXE isomer. The synthesis and distinct properties of E/Z isomers are beneficial to further development of new TPE derivatives for various applications

Covalent Patterning and Rapid Visualization of Latent Fingerprints with Photo-Cross-Linkable Semiconductor Polymer Dots

Fingerprint imaging and recognition represent the most important approach in personal identification. Here we designed and synthesized oxetane-functionalized semiconductor polymer dots (Ox-Pdots) for covalent patterning and rapid visualization of latent fingerprints. The high fluorescence brightness, large Stokes shift, and excellent surface properties of the Ox-Pdots lead to fingerprint imaging with high sensitivity and resolution. Fingerprint ridge structures with the first, second, and third levels of details were clearly developed within minutes. The method was facile and robust for visualization of fingerprints on various surfaces including glass, metal, and plastics. Moreover, the oxetane groups in the Ox-Pdots undergo cross-linking reactions induced by a short-time UV irradiation, yielding 3-D intermolecular polymer network. The resulting fingerprint patterns exhibit unparalleled stability against rigorous treatment, as compared to those by traditional Pdots. Our results demonstrate that the Ox-Pdots hold great promise for latent fingerprint imaging and fluorescence anticounterfeiting applications

Enhanced Phototherapy by Nanoparticle-Enzyme via Generation and Photolysis of Hydrogen Peroxide

Light has been widely used for cancer therapeutics such as photodynamic therapy (PDT) and photothermal therapy. This paper describes a strategy called enzyme-enhanced phototherapy (EEPT) for cancer treatment. We constructed a nanoparticle platform by covalent conjugation of glucose oxidase (GOx) to small polymer dots, which could be persistently immobilized into a tumor. While the malignant tumors have high glucose uptake, the GOx efficiently catalyzes the glucose oxidation with simultaneous generation of H₂O₂. Under light irradiation, the in situ generated H₂O₂ was photolyzed to produce hydroxyl radical, the most reactive oxygen species, for killing cancer cells. In vitro assays indicated that the cancer cells were destroyed by using a nanoparticle concentration at 0.2 μg/mL and a light dose of ∼120 J/cm², indicating the significantly enhanced efficiency of the EEPT method when compared to typical PDT that requires a photosensitizer of >10 μg/mL for effective cell killing under the same light dose. Furthermore, remarkable inhibition of tumor growth was observed in xenograft-bearing mice, indicating the promise of the EEPT approach for cancer therapeutics