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.

Natural Protein Photon Upconversion Supramolecular Assemblies for Background-Free Biosensing.

The diagnosis of disease biomarkers is crucial for the identification, monitoring, and prognostic assessment of malignant disease. However, biological samples with autofluorescence, complex components, and heterogeneity pose major challenges to reliable biosensing. Here, we report the self-assembly of natural proteins and the triplet-triplet annihilation upconversion (TTA-UC) pair to form upconverted protein clusters (∼8.2 ± 1.1 nm), which were further assembled into photon upconversion supramolecular assemblies (PUSA). This PUSA exhibited unique features, including a small size (∼44.1 ± 4.1 nm), oxygen tolerance, superior biocompatibility, and easy storage via lyophilization, all of which are long sought after for photon upconversion materials. Further, we have revealed that the steric hindrance of the annihilator suppresses the stacking of the annihilator in PUSA, which is vital for maintaining the water dispersibility and enhancing the upconversion performance of PUSA. In conjunction with sarcosine oxidase, this near infrared (NIR)-excitable PUSA nanoprobe could perform background-free biosensing of urinary sarcosine, which is a common biomarker for prostatic carcinoma (PCa). More importantly, this nanoprobe not only allows for qualitative identification of urinary samples from PCa patients by the unaided eye under NIR-light-emitting diode (LED) illumination but also quantifies the concentration of urinary sarcosine. These remarkable findings have propelled photon upconversion materials to a new evolutionary stage and expedited the progress of upconversion biosensing in clinical diagnostics.

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.

Precisely Tuning Band Gaps of Hexabenzocoronene-Based MOFs Toward Enhanced Photocatalysis.

Precise adjusting the band gaps in metal-organic frameworks (MOFs) is crucial for improving their visible-light absorption capacity during photocatalysis, presenting both a formidable challenge and a charming opportunity. This present study employed a symmetry-reduction strategy to pre-design six novel 4-connected ligands with systematic substituents (-NO2, -H, -tBu, -OCH3, -OH and -NH2) and synthesized the corresponding pillared-layer Zr-MOFs (NKM-668) retaining the hexaphenylbenzene fragment. Subsequently, the NKM-668 MOFs were transformed into large-π-conjugated hexabenzocoronene-based MOFs (pNKM-668) via the Scholl reaction. These twelve MOFs exhibited broad and tunable band gaps over 1.41 eV (ranging from 3.25 eV to 1.84 eV), and the photocatalytic CO2 conversion rate raised by 33.2-fold. This study not only enriches the type of hexaphenylbenzene-based MOFs, but also paves the way for nanographene-containing MOFs in the further application of photocatalysis.

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.

[Corrigendum] Circular RNAs in osteosarcoma: An update of recent studies (Review).

Subsequently to the publication of the above review, the authors have contacted the Editorial Office to explain that the article was regrettably published containing a few errors. First, on p. 3, left­hand column, the '3. Functions of circRNAs in OS' section, line 23, the sentence here should have read as follows (changes shown in bold, where appropriate): 'Circ_0001649 has been reported as a sponge of various miRNAs that inhibit cell proliferation (62,83).' (i.e., mentioning 'Circ_0001649' twice was an error/oversight). Secondly, in the '4. Mechanisms of circRNAs in OS' section, paragraph 5, line 23 on p. 8, the four consecutive sentences that start on this line should have read as follows: 'Hsa_circ_0000190 is significantly downregulated in OS tissues and cell lines. This circRNA inhibits the Wnt/ß­catenin signaling pathway by sponging miR­767­5p, the target of which is TET1 (61). And hsa_circ_0002052 can sponge miR­1205, the target of which is adenomatosis polyposis coli 2 (APC2), a negative regulator of the Wnt/ß­catenin signaling pathway. Hence, hsa_circ_0000190 and hsa_circ_0002052 can function as inhibitors of the Wnt/ß­catenin signaling pathway by promoting TET1 and APC2 expression via miRNA sponging, ultimately resulting in the delayed development of OS (50,61).' (i.e., the first sentence was corrected to read 'Hsa_circ_0000190' and 'hsa_circ_0000190' was added to the fourth sentence, and ref. 61 was added to the second sentence in this section, and included with ref. 50 at the end of the fourth sentence). Thirdly (and finally), changes were required to both Fig. 3 and its accompanying legend, and these are featured on the next page; essentially, 'CircRNA CDR1as (47)' should not have been included in the Fig. 3 legend as this circRNA is not described in the figure, and some changes have been made to the figure itself in terms of wrongly placed lines and arrows. The authors are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish this Corrigendum, and all the authors agree with its publication. Furthermore, the authors apologize to the readership for any inconvenience caused. [International Journal of Oncology 63: 123, 2023; DOI: 10.3892/ijo.2023.5571].

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.