N6-methyladenosine-driven miR-143/145-KLF4 circuit orchestrates the phenotypic switch of pulmonary artery smooth muscle cells.

Pulmonary hypertension (PH) is characterized by vascular remodeling predominantly driven by a phenotypic switching in pulmonary artery smooth muscle cells (PASMCs). However, the underlying mechanisms for this phenotypic alteration remain incompletely understood. Here, we identified that RNA methyltransferase METTL3 is significantly elevated in the lungs of hypoxic PH (HPH) mice and rats, as well as in the pulmonary arteries (PAs) of HPH rats. Targeted deletion of Mettl3 in smooth muscle cells exacerbated hemodynamic consequences of hypoxia-induced PH and accelerated pulmonary vascular remodeling in vivo. Additionally, the absence of METTL3 markedly induced phenotypic switching in PASMCs in vitro. Mechanistically, METTL3 depletion attenuated m6A modification and hindered the processing of pri-miR-143/145, leading to a downregulation of miR-143-3p and miR-145-5p. Inhibition of hnRNPA2B1, an m6A mediator involved in miRNA maturation, similarly resulted in a significant reduction of miR-143-3p and miR-145-5p. We demonstrated that miR-145-5p targets Krüppel-like factor 4 (KLF4) and miR-143-3p targets fascin actin-bundling protein 1 (FSCN1) in PASMCs. The decrease of miR-145-5p subsequently induced an upregulation of KLF4, which in turn suppressed miR-143/145 transcription, establishing a positive feedback circuit between KLF4 and miR-143/145. This regulatory circuit facilitates the persistent suppression of contractile marker genes, thereby sustaining PASMC phenotypic switch. Collectively, hypoxia-induced upregulation of METTL3, along with m6A mediated regulation of miR-143/145, might serve as a protective mechanism against phenotypic switch of PASMCs. Our results highlight a potential therapeutic strategy targeting m6A modified miR-143/145-KLF4 loop in the treatment of PH.

Dual Roles of the Photooxidation of Organic Amines for Enhanced Triplet-Triplet Annihilation Upconversion in Nanoparticles.

Oxygen-mediated triplet-triplet annihilation upconversion (TTA-UC) quenching limits the application of such organic upconversion materials. Here, we report that the photooxidation of organic amines is an effective and versatile strategy to suppress oxygen-mediated upconversion quenching in both organic solvents and aqueous solutions. The strategy is based on the dual role of organic amines in photooxidation, i.e., as singlet oxygen scavengers and electron donors. Under photoexcitation, the photosensitizer sensitizes oxygen to produce singlet oxygen for the oxidation of alkylamine, reducing the oxygen concentration. However, photoinduced electron transfer among photosensitizers, organic amines, and oxygen leads to the production of superoxide anions that suppress TTA-UC. To observe oxygen-tolerating TTA-UC, we find that alkyl secondary amines can balance the production of singlet oxygen and superoxide anions. We then utilize polyethyleneimine (PEI) to synthesize amphiphilic polymers to encapsulate TTA-UC pairs for the formation of water-dispersible, ultrasmall, and multicolor-emitting TTA-UC nanoparticles.

Near Infrared-II Excited Triplet Fusion Upconversion with Anti-Stokes Shift Approaching the Theoretical Limit.

The anti-Stokes shift represents the capacity of photon upconversion to convert low-energy photons to high-energy photons. Although triplet exciton-mediated photon upconversion presents outstanding performance in solar energy harvesting, photoredox catalysis, stereoscopic 3D printing, and disease therapeutics, the interfacial multistep triplet exciton transfer leads to exciton energy loss to suppress the anti-Stokes shift. Here, we report near infrared-II (NIR-II) excitable triplet exciton-mediated photon upconversion using a hybrid photosensitizer consisting of lead sulfide quantum dots (PbS QDs) and new surface ligands of thiophene-substituted diketopyrrolopyrrole (Th-DPP). Under 1064 nm excitation, this photon upconversion revealed a record-corrected upconversion efficiency of 0.37% (normalized to 100%), with the anti-Stokes shift (1.07 eV) approaching the theoretical limit (1.17 eV). The observation of this unexpected result is due to our discovery of the presence of a weak interaction between the sulfur atom on Th-DPP and Pb2+ on the PbS QDs surface, facilitating electronic coupling between PbS QDs and Th-DPP, such that the realization of triplet exciton transfer efficiency is close to 100% even when the energy gap is as small as 0.04 eV. With this premise, this photon upconversion as a photocatalyst enables the production of standing organic gel via photopolymerization under 1064 nm illumination, displaying NIR-II photon-driven photoredox catalysis. This research not only establishes the foundation for enhancing the performance of NIR-II excitable photonic upconversion but also promotes its development in photonics and photoredox catalysis.

N6-methyladenosine modification of KLF2 may contribute to endothelial-to-mesenchymal transition in pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a progressive disease characterized by pulmonary vascular remodeling. Increasing evidence indicates that endothelial-to-mesenchymal transition (EndMT) in pulmonary artery endothelial cells (PAECs) is a pivotal trigger initiating this remodeling. However, the regulatory mechanisms underlying EndMT in PH are still not fully understood. METHODS: Cytokine-induced hPAECs were assessed using RNA methylation quantification, qRT-PCR, and western blotting to determine the involvement of N6-methyladenosine (m6A) methylation in EndMT. Lentivirus-mediated silencing, overexpression, tube formation, and wound healing assays were utilized to investigate the function of METTL3 in EndMT. Endothelial-specific gene knockout, hemodynamic measurement, and immunostaining were performed to explore the roles of METTL3 in pulmonary vascular remodeling and PH. RNA-seq, RNA Immunoprecipitation-based qPCR, mRNA stability assay, m6A mutation, and dual-luciferase assays were employed to elucidate the mechanisms of RNA methylation in EndMT. RESULTS: The global levels of m6A and METTL3 expression were found to decrease in TNF-α- and TGF-ß1-induced EndMT in human PAECs (hPAECs). METTL3 inhibition led to reduced endothelial markers (CD31 and VE-cadherin) and increased mesenchymal markers (SM22 and N-cadherin) as well as EndMT-related transcription factors (Snail, Zeb1, Zeb2, and Slug). The endothelial-specific knockout of Mettl3 promoted EndMT and exacerbated pulmonary vascular remodeling and hypoxia-induced PH (HPH) in mice. Mechanistically, METTL3-mediated m6A modification of kruppel-like factor 2 (KLF2) plays a crucial role in the EndMT process. KLF2 overexpression increased CD31 and VE-cadherin levels while decreasing SM22, N-cadherin, and EndMT-related transcription factors, thereby mitigating EndMT in PH. Mutations in the m6A site of KLF2 mRNA compromise KLF2 expression, subsequently diminishing its protective effect against EndMT. Furthermore, KLF2 modulates SM22 expression through direct binding to its promoter. CONCLUSIONS: Our findings unveil a novel METTL3/KLF2 pathway critical for protecting hPAECs against EndMT, highlighting a promising avenue for therapeutic investigation in PH.

The "4+4" Medical Doctor (MD) Pilot Program at PUMC: Implementation, Performance, and Prospects.

Peking Union Medical College (PUMC) launched the "4+4" Medical Doctor (MD) pilot program in 2018, admitting students with non-medical backgrounds from top universities, aligning with national medical talent training policies to foster diverse and eager learners in medicine. On the occasion of the graduation of the first class of the "4+4" MD pilot class at PUMC in 2023, we reviewed the teaching reform in the pilot program and carried out a systematic survey and interviews with students, faculties, and management staff of the pilot class. This article reports on the measures taken by the pilot class at PUMC in enrollment and curriculum setting, and demonstrates the achievements of the pilot class in terms of student academic background structure, knowledge acquisition and skill learning, scientific research ability, and course evaluation. The results indicated that the pilot class had met the national demand for the "Medicine + X" talent training model. More specifically, with a diverse academic backgrounds, the pilot class graduates had academic levels comparable to the eight-year medical education graduates, and their scientific research abilities were satisfactory. The pilot program at PUMC will optimize the curriculum setting, strengthen the construction of faculty, learning resources, and teaching facilities, and reform the academic evaluation methods, thus deepening the reform of medical education and improving the "4+4" MD program as a novel medical education model.

Enhancing Triplet-Triplet Annihilation Upconversion: From Molecular Design to Present Applications.

Photon upconversion, the process of converting low-energy photons into high-energy ones, has been widely applied for solar energy conversion, photoredox catalysis, and various biological applications such as background-free bioimaging, cancer therapy, and optogenetics. Upconversion materials that are based on triplet-triplet annihilation (TTA) are of particular interest due to their low excitation power requirements (e.g., ambient sunlight) and easily tunable excitation and emission wavelengths. Despite advances that have been made with respect to TTA upconversion (TTA-UC) in the past decade, several challenges remain for near-infrared light-activatable triplet-triplet annihilation upconversion (NIR TTA-UC). These challenges include low upconversion quantum yield, small anti-Stokes shift, and incompatibility with oxygen, the latter of which seriously limits the practical applications of NIR TTA-UC.This Account will summarize the recent research endeavors to address the above-mentioned challenges and the recent new applications. The first part of this Account highlights recent strategies of molecular design to modulate the excited states of photosensitizers and annihilators, two key factors to determine TTA-UC performance. Novel molecular engineering strategies such as the resonance energy transfer method, dimerization of dye units, and the helix twist molecular structure have been proposed to tune the excited states of photosensitizers. The obtained photosensitizers exhibited enhanced absorption of deep tissue penetrable near-infrared (NIR) light, produced a triplet excited state with elevated energy level and prolonged lifetime, and promoted intersystem crossing, leading to an upgraded TTA-UC system with significantly expanded anti-Stokes shift. With respect to the annihilator, the perylene derivatives were systematically explored, and their attached aromatic groups were found to be the key to adjusting the energy levels of both the triplet and singlet excited states. The resultant optimal TTA-UC system exhibits the highest recorded efficiency among NIR TTA-UC systems.Moreover, to resolve the oxygen-induced TTA-UC quenching, enzymatic reactions were recently introduced. More specifically, the glucose oxidase-catalyzed glucose oxidation reaction showed the ability to rapidly consume oxygen to turn on the TTA-UC luminescence in an aqueous solution. The resultant TTA-UC nanoparticle was able to detect glucose and an enzyme related to glucose metabolism in a highly specific, sensitive, and background-free manner. Further, the upconverted singlet excited state of the annihilator was directly utilized as the catalyst or the excited substrate. For example, the modification of annihilators and drug molecules with photolabile linkages can realize the long wavelength light-induced photolysis. Compared to direct short-wavelength-driven photolysis, this sensitized TTA photolysis (TTAP) exhibits superior reaction yield and lower photodamage, which are important in the release of drugs for tumor treatment in vivo. Moreover, the improved upconversion efficiency can enable the successful coupling of NIR TTA-UC with a visible light absorbing photocatalyst for NIR-driven photoredox catalysis. Compared to direct visible-light photocatalysis, TTA-UC mediated NIR photoredox catalysis showed superior product yield especially in large scale reaction systems owing to the deep penetration power of NIR light. More interestingly, among a few promising technology applications, three-dimensional (3D) printing based on photopolymerization can operate with faster speed and energy-input several orders of magnitude lower when the two-photon polymerization is replaced with TTA-UC mediated polymerization. We believe this Account will spur interest in the further development and application of TTA-UC in the areas of energy, chemistry, material science, and biology.

Bodipy Dimer for Enhancing Triplet-Triplet Annihilation Upconversion Performance.

Triplet-triplet annihilation upconversion (TTA-UC) has considerable potential for emerging applications in bioimaging, optogenetics, photoredox catalysis, solar energy harvesting, etc. Fluoroboron dipyrrole (Bodipy) dyes are an essential type of annihilator in TTA-UC. However, conventional Bodipy dyes generally have large molar extinction coefficients and small Stokes shifts (<20 nm), subjecting them to severe internal filtration effects at high concentrations, and resulting in low upconversion quantum efficiency of TTA-UC systems using Bodipy dyes as annihilators. In this study, a Bodipy dimer (B-2) with large Stokes shifts was synthesized using the strategy of dimerization of an already reported Bodipy annihilator (B-1). Photophysical characterization and theoretical chemical analysis showed that both B-1 and B-2 can couple with the red light-activated photosensitizer PdTPBP to fulfill TTA-UC; however, the higher fluorescence quantum yield of B-2 resulted in a higher upconversion efficiency (ηUC) for PdTPBP/B-2 (10.7%) than for PdTPBP/B-1 (4.0%). This study proposes a new strategy to expand Bodipy Stokes shifts and improve TTA-UC performance, which can facilitate the application of TTA-UC in photonics and biophotonics.

NIR-Absorbing B,N-Heteroarene as Photosensitizer for High-Performance NIR-to-Blue Triplet-Triplet Annihilation Upconversion.

Triplet-triplet annihilation upconversion (TTA-UC) with near-infrared (NIR) photosensitizers is highly desirable for a variety of emerging applications. However, the development of NIR-to-blue TTA-UC with a large anti-Stokes shift is extremely challenging because of the energy loss during the intersystem crossing (ISC). Here, we develop the first NIR-absorbing B,N-heteroarene-based sensitizer (BNS) with multi-resonance thermally activated delayed fluorescence (MR-TADF) characters to achieve efficient NIR-to-blue TTA-UC. The small energy gap between the singlet and triplet excited states (0.14 eV) of BNS suppresses the ISC energy loss, and its long-delayed fluorescence lifetime (115 µs) contributes to efficient triplet energy transfer. As a result, the largest anti-Stokes shift (1.03 eV) among all heavy-atom-free NIR-activatable TTA-UC systems is obtained with a high TTA-UC quantum yield of 2.9 % (upper limit 50 %).

Metal-Free Far-Red Light-Driven Photolysis via Triplet Fusion to Enhance Checkpoint Blockade Immunotherapy.

Metal-free long-wavelength light-driven prodrug photoactivation is highly desirable for applications such as neuromodulation, drug delivery, and cancer therapy. Herein, via triplet fusion, we report on the far-red light-driven photo-release of an anti-cancer drug by coupling the boron-dipyrromethene (BODIPY)-based photosensitizer with a photocleavable perylene-based anti-cancer drug. Notably, this metal-free triplet fusion photolysis (TFP) strategy can be further advanced by incorporating an additional functional dopant, i.e. an immunotherapy medicine inhibiting the indoleamine 2,3-dioxygenase (IDO), with the far-red responsive triplet fusion pair in an air-stable nanoparticle. With this IDO inhibitor-assisted TFP system we observed efficient inhibition of primary and distant tumors in a mouse model at record-low excitation power, compared to other photo-assisted immunotherapy approaches. This metal-free TFP strategy will spur advancement in photonics and biophotonics fields.

Tetrazole-Containing Triphenylamine-Based MOF as a Sensitive Sensor for Food Inspection.

A new metal-organic framework (MOF) with tetrazole-derived triphenylamine (TPA) as the ligand, namely Mn-TPA, has been successfully prepared and thoroughly characterized via thermogravimetric analysis, IR spectroscopy, elemental analysis, UV-vis absorption, fluorescence analysis, bond valence sum calculations, and single-crystal and powder X-ray diffraction analysis. The undulating monolayer of Mn-TPA can hinder the interaction and tight stacking among analytes, which creates a bionic microenvironment for the electrochemical recognition process. Mn-TPA exhibits high specific surface area, stable film-forming capacity, excellent electrochemical activity, and good biocompatibility. Furthermore, the developed Mn-TPA-based immunosensing system exhibits an excellent limit of detection of 0.50 pg·mL-1 toward vomitoxin, which is more outstanding than that of the reported vomitoxin-sensing system. Thus, this work shows the great potential of a well-designed MOF as an easy-to-make and highly sensitive electrochemical platform for biosensing in food safety detection and other fields.

Direct Utilization of Near-Infrared Light for Photooxidation with a Metal-Free Photocatalyst.

Near-infrared (NIR) light-triggered photoredox catalysis is highly desirable because NIR light occupies almost 50% of solar energy and possesses excellent penetrating power in various media. Herein we utilize a metal-free boron dipyrromethene (BODIPY) derivative as the photocatalyst to achieve NIR light (720 nm LED)-driven oxidation of benzylamine derivatives, sulfides, and aryl boronic acids. Compared to blue light-driven photooxidation using Ru(bpy)3Cl2 as a photocatalyst, NIR light-driven photooxidation exhibited solvent independence and superior performance in large-volume (20 mL) reaction, presumably thanks to the neutral structure of a BODIPY photocatalyst and the deeper penetration depth of NIR light. We further demonstrate the application of this metal-free NIR photooxidation to prodrug activation and combination with Cu-catalysis for cross coupling reaction, exhibiting the potential of metal-free NIR photooxidation as a toolbox for organic synthesis and drug development.

A novel tonicity-responsive microRNA miR-23a-5p modulates renal cell survival under osmotic stress through targeting heat shock protein 70 HSPA1B.

There is growing evidence that microRNAs (miRNAs) are implicated in cellular adaptation to osmotic stress, but the underlying osmosignaling pathways are still not completely understood. In this study, we found that a passenger strand miRNA, miR-23a-5p, was significantly downregulated in response to high NaCl treatment in mouse inner medullary collecting duct cells (mIMCD3) through an miRNA profiling assay. The decrease of miR-23a-5p is hypertonicity-dependent and osmotolerant cell type-specific. Knockdown of miR-23a-5p increased cellular survival and proliferation in mIMCD3. In contrast, miR-23a-5p overexpression repressed cell viability and proliferation under hypertonic stress. RNA deep-sequencing revealed that a heat shock protein 70 (HSP70) isoform, HSP70 member 1B (HSPA1B), was significantly increased under hypertonic treatment. Based on the prediction analysis by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and TargetScan, and a further validation via a dual-luciferase assay, HSPA1B was identified as a potential target of miR-23a-5p. Overexpressed miR-23a-5p suppressed HSPA1B, whereas downregulated miR-23a-5p promoted HSPA1B expression in mIMCD3. In addition, an in vivo study demonstrated that there is a reverse correlation between the levels of miR-23a-5p and HSPA1B in mouse renal inner medulla (papilla) that is exposed to extremely high osmolality. In summary, this study elucidates that passenger strand miR-23a-5p is a novel tonicity-responsive miRNA. The downregulation of miR-23a-5p facilitates cellular adaptation to hypertonic stress in mammalian renal cells through modulating HSPA1B.

Self-Assembled Metal-Organic Framework Stabilized Organic Cocrystals for Biological Phototherapy.

Organic self-assembled co-crystals have garnered considerable attention due to their facile synthesis and intriguing properties, but supramolecular interactions restrict their stability in aqueous solution, which is especially important for biological applications. Herein, we report on the first biological application of aqueous dispersible self-assembled organic co-crystals via the construction of metal-organic framework (MOF) -stabilized co-crystals. In particular, we built an electron-deficient MOF with naphthalene diimide (NDI) as the ligand and biocompatible Ca2+ as the metal nodes. An electron donor molecule, pyrene, was encapsulated to form the host-guest MOF self-assembled co-crystal. We observed that such MOF structure leads to uniquely high-density ordered arrangement and the close intermolecular distance (3.47 Å) of the charge transfer pairs. Hence, the concomitant superior charge transfer interaction between pyrene/NDI can be attained and the resultant photothermal conversion efficiency of Py@Ca-NDI in aqueous solution can thus reach up to 41.8 %, which, to the best of our knowledge, is the highest value among the reported organic co-crystal materials; it is also much higher than that of the FDA approved photothermal agent ICG as well as most of the reported MOFs. Based on this realization, as a proof of concept, we demonstrated that such a self-assembled organic co-crystal platform can be used in biological applications that are exemplified via highly effective long wavelength light photothermal therapy.

Highly Effective Near-Infrared Activating Triplet-Triplet Annihilation Upconversion for Photoredox Catalysis.

Organic triplet-triplet annihilation upconversion (TTA-UC) materials have considerable promise in areas as broad as biology, solar energy harvesting, and photocatalysis. However, the development of highly efficient near-infrared (NIR) light activatable TTA-UC systems remains extremely challenging. In this work, we report on a method of systematically tailoring an annihilator to attain such outstanding systems. By chemical modifications of a commonly used perylene annihilator, we constructed a family of perylene derivatives that have simultaneously tailored triplet excited state energy (T1) and singlet excited state energy (S1), two key annihilator factors to determine TTA-UC performance. Via this method, we were able to tune the TTA-UC system from an endothermic type to an exothermic one, thus significantly elevating the upconversion performance of NIR light activatable TTA upconversion systems. In conjunction with the photosensitizer PdTNP (10 µM), the upconversion efficiency using the optimal annihilator (100 µM) identified in this study was measured to be 14.1% under the low-power density of NIR light (100 mW/cm2, 720 nm). Furthermore, using such a low concentration of perylene derivative, we demonstrated that the optimal TTA-UC pair developed in our study can act as a highly effective light wavelength up-shifter to enable NIR light to drive a photoredox catalysis that otherwise requires visible light. We found that such an NIR driven method is highly effective and can even surpass directly visible light driven photoredox catalysis. This method is important for photoredox catalysis as NIR light can penetrate much deeper in colored photoredox catalysis reaction solutions, especially when done in a large-scale manner. Furthermore, this TTA-UC mediated photoredox catalysis reaction is found to be outdoor sunlight operable. Thus, our study provides a solution to enhance NIR activatable organic upconversion and set the stage for a wide array of applications that have previously been limited by the suboptimal efficiency of the existing TTA upconversion materials.

Organized Aggregation Makes Insoluble Perylene Diimide Efficient for the Reduction of Aryl Halides via Consecutive Visible Light-Induced Electron-Transfer Processes.

The consecutive photo-induced electron-transfer (conPET) process found with perylene diimide (PDI) overcomes the limitation of visible-light photocatalysis and sheds light on effective solar energy conversion. By the incorporation of PDI into a metal-organic polymer Zn-PDI, a heterogeneous approach was achieved to tackle the poor solubility and strong tendency to aggregate of PDIs that restricted the exploitation of this outstanding homogeneous process. The interplay between metal-PDI coordination and π···π stacking of the organized PDI arrays in Zn-PDI facilitates the conPET process for the visible light-driven reduction of aryl halides by stabilizing the radical-anion intermediate and catalyst-substrate interacted moiety. These synergistic effects between the PDI arrays and Zn sites further render Zn-PDI photoactivity for fundamental oxidation of benzyl alcohols and amines. The tunable and modular nature of the two-dimensional metal-organic polymers makes the catalyst-embedding strategy promising for the development of ideal photocatalysts toward the better utilization of solar energy.

Overexpression of miR-122 promotes the hepatic differentiation and maturation of mouse ESCs through a miR-122/FoxA1/HNF4a-positive feedback loop.

BACKGROUND & AIMS: microRNA-122 is the only identified liver-specific miRNA and plays a crucial role in liver development, maintenance of hepatic homeostasis as well as tumourigenesis. In our previous differentiation of ESCs into hepatocytes, microRNA-122 (miR-122) was expressed at a relatively low level. Here, we aim to elucidate the effect and underlying mechanisms of miR-122 during differentiation of ESCs into hepatocytes. METHODS: Mouse ESCs were initially induced towards HPCs by activin A, FGF-4 and sodium butyrate and were subsequently transfected with a recombinant adenovirus expressing vector pAV.Ex1d-CMV>miR-122/IRES/eGFP 9 days after induction. Cells were analysed by real-time PCR, immunofluorescence, flow cytometry, microscopy and functional assays. Furthermore, microarray analysis was performed. RESULTS: We demonstrated that overexpression of miR-122 could effectively promote hepatic differentiation and maturation, as assessed by morphological and functional tests. The microarray analysis revealed that 323 genes were down-regulated, whereas 59 were up-regulated. Particularly, two liver-specific transcription factors, FoxA1 and HNF4a, were significantly up-regulated. Moreover, the expression of E-cadherin was dramatically increased and the proliferation of HPCs was suppressed, whereas knockdown of FoxA1 reduced E-cadherin expression and increased the proliferation of HPCs. In addition, the expression levels of FoxA1, HNF4a and E-cadherin in time-course transfection experiments with miR-122 were not significantly increased except in cells in which transfection with miR-122 occurred 9 days after induction. CONCLUSION: Overexpression of miR-122 at an appropriate stage could promote hepatic differentiation and maturation by regulating the balance between proliferation and differentiation, as well as the balance between EMT and MET, partially through a miR-122/FoxA1/HNF4a-positive feedback loop.

New Type Annihilator of π-Expanded Diketopyrrolopyrrole for Robust Photostable NIR-Excitable Triplet-Triplet Annihilation Upconversion.

Near-infrared light excitable triplet-triplet annihilation upconversion (NIR TTA-UC) materials have attracted interest in a variety of emerging applications such as photoredox catalysis, optogenetics, and stereoscopic 3D printing. Currently, the practical application of NIR TTA-UC materials requires substantial improvement in photostability. Here, we found that the new annihilator of π-expanded diketopyrrolopyrrole (π-DPP) cannot activate oxygen to generate superoxide anion via photoinduced electron transfer, and its electron-deficient characteristics prevent the singlet oxygen-mediated [2 + 2] cycloaddition reaction; thus, π-DPP exhibited superior resistance to photobleaching. In conjunction with the NIR photosensitizer PdTNP, the upconversion efficiency of π-DPP is as high as 8.9%, which is eight times of the previously reported PdPc/Furan-DPP. Importantly, after polystyrene film encapsulation, less than 10% photobleaching was observed for this PdTNP/π-DPP-based NIR TTA-UC material after four hours of intensive NIR light exposure. These findings provide a type of annihilator with extraordinary photostability, facilitating the development of NIR TTA-UC materials for practical photonics.

Rehabilitation exercises for kidney transplant recipients in an organ transplant ward: a best practice implementation project.

INTRODUCTION AND OBJECTIVES: Kidney transplantation is an effective treatment for end-stage kidney disease. Kidney transplant recipients (KTRs) are prone to experiencing reduced physical function, depression, fatigue, and lack of exercise motivation due to their sedentary lifestyle before surgery. Exercise is an effective intervention for KTRs, but it has not been properly implemented in many practice settings. This project aimed to promote evidence-based exercises as part of KTRs' rehabilitation to improve their health outcomes. METHODS: This project was informed by the JBI Evidence Implementation Framework. The project was conducted in the organ transplant ward of a tertiary comprehensive hospital in Changsha, China. Based on a summary of best evidence, 12 audit criteria were developed for the baseline and follow-up audits involving 30 patients and 20 nursing staff. The JBI Practical Application of Clinical Evidence System (PACES) and Getting Research into Practice (GRiP) tool were used to identify barriers and facilitators and develop targeted strategies to improve issues. RESULTS: Compared with the baseline audit, significant improvements were achieved in most of the criteria in the follow-up audit, with 9 of the 12 criteria reaching 100% compliance. Notably, the 6-minute walk distance test results were significantly higher, while the Self-Rating Depression Scale and Self-Rating Anxiety Scale scores were significantly lower (p < 0.05). CONCLUSIONS: This project demonstrates that evidence-based practice can improve the clinical practice of rehabilitation exercises for KTRs. The GRiP strategies proved to be extremely useful, notably, the formulation of a standardized rehabilitation exercise protocol, training, and enhancement of the exercising environment. Head nurses' leadership and decision-making also played an important role in the success of this project. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A180.

Differential neuronal expression of receptor interacting protein 3 in rat retina: involvement in ischemic stress response.

BACKGROUND: Receptor-interacting protein 3 (RIP3), a member of RIP family proteins, has been shown to participate in programmed necrosis or necroptosis in cell biology studies. Evidence suggests that necroptosis may be a mode of neuronal death in the retina. RESULTS: In the present study we determined the expression of RIP3 in normal rat retina and its changes following acute high intraocular pressure (aHIOP). RIP3 immunoreactivity (IR) was largely present in the inner retinal layers, localized to subsets of cells expressing neuron-specific nuclear antigen (NeuN), parvalbumin and calbindin in the ganglion cell layer (GCL) and inner nuclear layer (INL). No double labeling was detected for RIP3 with PKC-α or rhodopsin. RIP3 immunoreactivity was increased in the GCL at 6 hr and 12 hr, but reduced at 24 hr in the retina, without apparent alteration in laminar or cellular distribution pattern. Western blot analysis confirmed the above time-dependent alteration in RIP3 protein expression. RIP3 expressing cells frequently co-localized with propidium iodide (PI). A few co-localized cells were observed between RIP3 and Bax or cleaved caspase-3 in the GCL in 12 hr following aHIOP. CONCLUSIONS: The results indicate that RIP3 is expressed differentially in retinal neurons in adult rats, including subsets of ganglion cells, amacrine and horizontal cells. RIP3 protein levels are elevated rapidly following aHIOP. RIP3 labeling co-localized with PI, Bax or cleaved caspase-3 among cells in the ganglion cell layer following aHIOP, which suggest its involvement of RIP3 in neuronal responses to acute ischemic insults.

[The clinic research of the modified laparoscopic splenectomy for massive splenomegaly in the treatment of children with hematologic diseases].

OBJECTIVE: To summarize the experience and characteristics of the modified laparoscopic splenectomy for massive splenomegaly in the treatment of children with hematologic disease. METHODS: The clinical data of 30 cases of laparoscopic splenectomy for massive splenomegaly of children with hematologic disease from March 2007 to December 2011 was analyzed retrospectively. There were 18 male and 12 female patients, aging from 2 to 14 years. Primary disease included mediterranean anemia (17 cases), hereditary spherocytosis (4 cases) and idiopathic thrombocytopenic purpura (ITP, 9 cases). Dissection started with cutting off the gastrosplenic ligaments and lesser sac to fully reveal the splenic hilum, the splenic artery was clamped twice with 10 mm tiatanum clamp. When most of blood stored in the spleen back to heart through the veins and the splenic volume had already decreased, the splenic vein was ligated with 10 mm titanium clip and cut with ligsure and splenic pedicle separated. The Surgery and complication were recorded. For 1 week after surgery, the hemoglobin and platelet counts were reviewed. RESULTS: Twenty-six cases were performed successfully, and 4 cases were converted to open procedure. Of the 4 cases, 2 cases was obesity because of idiopathic thrombocytopenic purpura, 1 case was ß thalassaemia combined severe liver enlargement, and 1 case was after partial splenic embolization. In cases of laparoscopic splenectomy, operation time was 110 to 130 minutes, with an average of 120 minutes, and blood loss during operation was 35 to 180 ml, with an average of 45 ml. Compared with pre-operation, the hemoglobin of mediterranean anemia and hereditary spherocytosis patients were (92 ± 8) g/L, and blood platelet count of ITP patients was (127 ± 20)×10(9)/L, and they increased obviously at 1 week after operation (t = 4.175 and 8.253, both P = 0.000). CONCLUSION: The modified surgical method make the laparoscopic splenectomy for massive splenomegaly in many children with hematologic diseases possible, which was thought to be impossible in the past.