Tannic Acid-Based Self-Assembling Nanocarriers with Antiphotobleaching and Controlled Releasing Properties for Collaborative Near-Infrared Photothermal/Photodynamic Therapy.

Near-infrared (NIR) organic materials have been widely developed for tumor phototherapy due to their deep tumor penetration, good biodegradability, and high photothermal conversion (PCE). However, most of the NIR organic dyes are easily destroyed by photooxidation due to their big and long conjugated structures, such as cyanine dyes. Under light irradiation, the reactive oxygen species (ROS) produced by these NIR dyes can easily break their conjugated skeleton, resulting in a dramatic decrease in phototherapeutic efficiency. Herein, an NIR organic dye cyanine dye (CyS) and a photosensitizer methylene blue (MB) were chosen to prepare nanocarrier CMTNPs by facile self-assembling with a natural antioxidant, tannic acid (TA). TA can greatly enhance the stability of NIR cyanine dyes by scavenging ROS. Furthermore, CMTNPs have a character of pH/thermal dual response, allowing for controlled release of MB in the slightly acidic tumor environment during photothermal therapy. The released MB can turn on both fluorescence and photodynamic therapy effects. In vitro and in vivo experiments demonstrated the remarkable tumor ablation ability of CMTNPs. Thus, our study provided an antiphotobleaching and controlled release photosensitizer strategy through the introduction of antioxidant TA into the nanocarrier for efficient collaborative photothermal/photodynamic therapy.

Self-assembly-integrated tumor targeting and electron transfer programming towards boosting tumor type I photodynamic therapy.

Type I photodynamic therapy (PDT) is attracting increasing interest as an effective solution to the poor prognosis of patients with hypoxic tumors. The development of functional type I photosensitizers is limited by a lack of feasible strategies to systematically modulate electron transfer (ET) in photosensitization. Herein, we present an easily accessible approach for the preparation of nanophotosensitizers with self-assembly-integrated tumor-targeting and ET programming towards boosting tumor type I PDT. Specifically, a dual functional amphiphile PS-02 was designed with a ligand (6-NS) that had the ability to not only target tumor cell marker carbonic anhydrase IX (CAIX) but also regulate the ET process for type I PDT. The amphiphile PS-02 tended to self-assemble into PS-02 nanoparticles (NPs), which exhibited a local "ET-cage effect" due to the electron-deficient nature of 6-NS. It is noteworthy that when PS-02 NPs selectively targeted the tumor cells, the CAIX binding enabled the uncaging of the inhibited ET process owing to the electron-rich characteristic of CAIX. Therefore, PS-02 NPs integrated tumor targeting and CAIX activation towards boosting type I PDT. As a proof of concept, the improved PDT performance of PS-02 NPs was demonstrated with tumor cells under hypoxic conditions and solid tumor tissue in mouse in vivo experiments. This work provides a practical paradigm to develop versatile type I PDT nano-photosensitizers by simply manipulating ET and easy self-assembling.

Suppressing ACQ of molecular photosensitizers by distorting the conjugated-plane for enhanced tumor photodynamic therapy.

Non-AIE-type molecular photosensitizers (PSs) suffer from the aggregation-caused-quenching (ACQ) effect in an aqueous medium due to the strong hydrophobic and π-π interactions of their conjugated planes, which significantly hinders the enhancement of tumor photodynamic therapy (PDT). So far, some ionic PSs have been reported with good water-solubility, though the ACQ effect can still be induced in a biological environment rich in ions, leading to unsatisfactory in vivo delivery and fluorescence imaging performance. Hence, designing molecular PSs with outstanding anti-ACQ properties in water is highly desirable, but it remains a tough challenge for non-AIE-type fluorophores. Herein, we demonstrated a strategy for the design of porphyrin-type molecular PSs with remarkable solubility and anti-ACQ properties in an aqueous medium, which was assisted by quantum chemical simulations. It was found that cationic branched side chains can induce serious plane distortion in diphenyl porphyrin (DPP), which was not observed for tetraphenyl porphyrin (TPP) with the same side chains. Moreover, the hydrophilicity of the chain spacer is also crucial to the plane distortion for attaining the desired anti-ACQ properties. Compared to ACQ porphyrin, anti-ACQ porphyrin displayed type-I ROS generation in hypoxia and much higher tumor accumulation efficacy by blood circulation, leading to highly efficient in vivo PDT for hypoxic tumors. This study demonstrates the power of sidechain chemistry in tuning the configuration and aggregation behaviors of porphyrins in water, offering a new path to boost the performance of PSs to fulfill the increasing clinical demands on cancer theranostics.

Type-I Photodynamic Therapy Induced by Pt-Coordination of Type-II Photosensitizers into Supramolecular Complexes.

Platinum supramolecular complexes based on photosensitizers have garnered great interest in photodynamic therapy (PDT) due to Pt (II) centers as chemotherapeutic agents to eliminate tumor cells completely, which greatly improve the antitumor efficacy of PDT. However, in comparison to precursor photosensitizer ligand, the formed platinum supramolecular complexes typically exhibit inferior outcomes in terms of reactive oxygen species (ROS) generation. How to boost ROS generation in the formed platinum supramolecular complexes for enhanced PDT is an enticing yet highly challenging task. Here we report a Pt-coordination-based dimeric photosensitizer complex (Cz-BTZ-Py)2Pt(OTf)2. It is found that comparing with photosensitizer ligand Cz-BTZ-Py, the formed supramolecular complex exhibit redshifts of absorption wavelength as well as enhanced ROS generation efficiency. Moreover, type-I ROS generation (O2⋅-) is produced in the formed platinum supramolecular complexes mainly due to a reduced energy gap ΔEST resulting from exciton coupling between two photosensitizer ligands. And type-I ROS (O2⋅-) generation significantly amplifies the photodynamic therapy (PDT) outcomes. In vitro evaluation shows excellent photochemotherapy performance of (Cz-BTZ-Py)2Pt(OTf)2 nanoparticles. We anticipate this work would provide a novel approach to design type-I photosensitizers for efficient PDT.

Dual-Responsive hollow mesoporous organosilicon nanocarriers for photodynamic therapy.

HYPOTHESIS: The nano-delivery platform, -SS-HMONs@MB@MnO2 nanoparticles (SMM NPs) loaded with methylene blue (MB) as photosensitizer have excellent photodynamic therapy (PDT) effect. The disulfide bond and MnO2 give the shell redox-responsive properties. SMM NPs consume glutathione (GSH) in tumor cells, reducing the scavenging of reactive oxygen species (ROS) by GSH and enhancing the PDT effect of MB. EXPERIMENTS: The GSH dual-responsive nano-delivery platform, was designed and constructed by using disulfide-doped hollow mesoporous organosilicon nanoparticles (-SS-HMONs) as intermediate responsive layer, loaded with MB as photosensitizer and coated with MnO2 as shells. The MB photosensitizer release and GSH response were characterized. The PDT effect of nanoparticles was evaluated. FINDINGS: The SMM NPs were uniform in size and well dispersed. The nanoparticles could react with GSH, leading to the decomposition of MnO2 shells and the breakage of disulfide bonds in -SS-HMONs, resulted in the release of MB photosensitizer. The cell experiment showed that SMM NPs had good ROS generating ability and PDT effect after being sucked by tumor cells, which could effectively kill tumor cells. However, in vivo experiments demonstrated that SMM NPs showed slight inhibition on tumor growth. The actual effect in animals was different from the effect in cells.

Configuration-mediated excited-state energy dissipation in metal-bridged dimeric D-A fluorophores for enhanced photothermal therapy.

Photothermal agents (PTAs) based on donor (D)-acceptor (A) NIR fluorophores show great promise in photothermal therapy due to their accessible molecular engineering to mediate excitation energy for high photothermal conversion. Except for molecular structural modification of D-A fluorophores, intermolecular arrangement in space greatly influences their excitation energy dissipation as well. But how to mediate their intermolecular arrangement is still challenging. Here we control the intermolecular orientation of chromophores via metal coordination to form Pt-bridged dimeric D-A fluorophores with different geometries. The formed configuration isomers show different intermolecular exciton coupling behaviors involving charge transfer (CT) evolution and internally limited molecular rotation, which greatly affect excited-energy dissipation. Compared with folded configuration with intense NIR emission (quantum yields (QYs) = 15.62 %), linear configuration favors non-radiative decays with low QYs (6.99 %) but enhanced photothermal conversion efficiency (PCE = 41.57 %). The self-assembled nanoparticles combining Pt-bridged dimeric D-A fluorophores with DSPE-PEG2000-RGD reveal superior photothermal therapeutic features with desirable biosafety. This research provides a new designing concept to mediate excited-state energy dissipation pathways at a sub-nano level for enhanced photothermal conversion. STATEMENT OF SIGNIFICANCE: D-A fluorophores as photothermal agents attract great attention in photothermal therapy due to their accessible molecular engineering. Besides molecular engineering of D-A fluorophores, the intermolecular packing manner is proven to greatly affect their excitation energy dissipation. But how to control intermolecular arrangement is still challenging. Here we control the intermolecular orientation of chromophores via metal coordination to form Pt-bridged dimeric D-A fluorophores with different geometries. Compared to the folded configuration, linear configuration facilitates charge transfer (CT) evolution and molecular rotation, which promotes non-radiative decays of excited energy for enhanced photothermal therapy.

DCX variants in two unrelated Chinese families with subcortical band heterotopia: Two case reports and review of literature.

Introduction: Subcortical band heterotopia (SBH) is a rare brain developmental malformation caused by deficient neuronal migration during embryogenesis. Published literature on pediatric SBH cases caused by DCX mutations is limited. Methods: The detailed clinical and genetic features of two pediatric SBH with DCX mutations were analyzed. The available literature on DCX mutations was reviewed. Results: Both patients were girls with varying degrees of developmental delay. Patient 1 was short in stature with peculiar facial features. Patient 2 had an early seizure onset and developed drug-resistant epilepsy. Whole-exome sequencing (WES) revealed two de novo heterozygous variants of DCX (NM_178153.3), including a novel missense variant of c.568A > G (p.K190E) in P1 and a reported nonsense variant of c.814C > T (p.R272*) in P2. We reviewed all the available literature regarding DCX mutations. A total of 153 different mutations have been reported, with the majority of 99 (64.7 %) being missense mutations. Conclusion: Our study expanded the mutational spectrum of DCX, which has important implications for the study of genotype-phenotype correlations. Furthermore, it provided insights to better understand SBH and genetic counseling.

Exploring Linker-Group-Guided Self-Assembly of Ultrathin 2D Supramolecular Nanosheets in Water for Synergistic Cancer Phototherapy.

Water is ubiquitous in natural systems where it builds an essential environment supporting biological supramolecular polymers to function, transport, and exchange. However, this extreme polar environment becomes a hindrance for the superhydrophobic functional π-conjugated molecules, causing significant negative impacts on regulating their aggregation pathways, structures, and properties of the subsequently assembled nanomaterials. It especially makes the self-assembly of ultrathin two-dimensional (2D) functional nanomaterials by π-conjugated molecules a grand challenge in water, although ultrathin 2D functional nanomaterials have exhibited unique and superior properties. Herein, we demonstrate the organic solvent-free self-assembly of one-molecule-thick 2D nanosheets based on exploring how side chain modifications rule the aggregation behaviors of π-conjugated macrocycles in water. Through an in-depth understanding of the roles of linking groups for side chains on affecting the aggregation behaviors of porphyrins in water, the regulation of molecular arrangement in the aggregated state (H- or J-type aggregation) was attained. Moreover, by arranging ionic porphyrins into 2D single layers through J-aggregation, the ultrathin nanosheets (thickness ≈ 2 nm) with excellent solubility and stability were self-assembled in pure water, which demonstrated both outstanding 1O2 generation and photothermal capability. The ultrathin nanosheets were further investigated as metal- and carrier-free nanodrugs for synergetic phototherapies of cancers both in vitro and in vivo, which are highly desirable by combining the advantages and avoiding the disadvantages of the single use of PDT or PTT.

Efficient adsorption of azo anionic dye Congo Red by micro-nano metal-organic framework MIL-68(Fe) and MIL-68(Fe)/chitosan composite sponge: Preparation, characterization and adsorption performance.

Micro-nano metal-organic framework (MIL-68(Fe)) for efficient adsorption of azo anionic dye Congo red (CR) was successfully prepared by one-step hydrothermal method under acidic environment. And a MIL-68(Fe)/chitosan composite sponge (MIL-68(Fe)/CS) was prepared under the coating of chitosan (CS). After comparing the performance of MIL-68(Fe) and MIL-68(Fe)/CS, we focus on exploring MIL-68(Fe)/CS. It ensured the CR removal efficiency while reaching the adsorption equilibrium faster than MIL-68(Fe), and solved the defect that the powder was difficult to be stripped by water after adsorption. The physicochemical properties and surface morphology of the adsorbent were characterized by SEM, FTIR, XRD, TGA, BET, and Zeta potential. The effects of pH, contact time, adsorbent dosage, initial solution concentration and temperature on the adsorption performance of the adsorbent were systematically analyzed. The pseudo-second-order model and the Sips model were most consistent for the adsorption process, indicating that the adsorption process of MIL-68(Fe)/chitosan composite sponge on CR is a complex physicochemical process. The removal rates of CR by MIL-68(Fe) and MIL-68(Fe)/chitosan composite sponge reached the maximum values of 99.55 % and 99.51 % at 318 K, respectively. And the maximum adsorption capacity of CR by MIL-68(Fe)/chitosan composite sponge at 318 K was 1184.16 mg·g-1. After six cycles of adsorption and desorption, the removal rate of CR was still higher than 80 %. The synergistic effects of π-π stacking, electrostatic interactions, hydrogen bonding and pore filling have important effects on CR removal.

Antimicrobial protection of two controlled release silver nanoparticles on simulated silk cultural relic.

HYPOTHESIS: Silver nanoparticles coated with organic-inorganic hybrid silica or inorganic silica have antimicrobial ability, and the coating can also effectively improve the dispersion and stability of the particles. The slow release of silver ions (Ag+) can improve the antimicrobial activity of silver nanoparticles. The synthesized nanoparticles are light yellow, which does not affect the look and feel of the silk cultural relics and meets the requirements of the principle of minimum interference. EXPERIMENTS: Two kinds of silver-based nanoparticles were synthesized: silver core-shell nanoparticle (Ag@mSiO2) and silver yolk-shell nanoparticle (Ag@YSiO2). The morphology, surface properties and Ag+ release efficiency of two nanoparticles were characterized. The antimicrobial effects of two nanoparticles on Aspergillus niger (A. niger) and Penicillium citrinum (P. citrinum) were compared. FINDINGS: Both of Ag@mSiO2 and Ag@YSiO2 had uniform size and good stability. Two nanoparticles had pore structure and silver nanocore, which provided the basis for the dissolution and exchange of Ag+. Because more silver ions were released, Ag@mSiO2 had higher antimicrobial activity than Ag@YSiO2 for A. niger and P. citrinum. For various silk samples, Ag@mSiO2 exhibited excellent antimicrobial properties. Meanwhile, there was little change in the color and tearing strength of Ag@mSiO2 coated silk.

Metal-Coordination-Mediated H-Aggregates of Cyanine Dyes for Effective Photothermal Therapy.

Integration of cyanine dyes and metal ions into one nanoplatform via metal-coordination interactions is an effective strategy to build multimodality phototheranostics. The multifunctionalities of the formed nanoscale metal-organic particles (NMOPs) have been widely explored. However, the effect of metal-coordination interaction on the aggregation behavior of cyanine dyes is rarely reported. Herein, we reported the H-aggregation behavior of cyanine dye Cy-3COOH induced by different metal ions M (Fe2+ or Mn2+ ). Moreover, the extent of H-aggregates varied with different metal-coordination interactions. Upon NIR irradiation, H-aggregates of Cy-3COOH remarkably promoted photothermal conversion efficiency. Interestingly, we also find that H-aggregates of Cy-3COOH induced by metal ions can generate the reactive oxygen species (ROS) involving singlet oxygen (1 O2 ) and superoxide anion radical (O2 - ⋅) upon light irradiation. In addition, the ROS efficiency varies depending on the extent of H-aggregates. Additionally, the photoinduced ROS could disassemble aggregates and decompose cyanine dye Cy-3COOH, which limits the photothermal capability of Cy-3COOH/M NPs. Therefore, the photothermal performance of Cy-3COOH/M NPs could be manipulated by the degree of H-aggregation. This would provide a new insight to develop efficient phototheranostics NMOPs for cancer treatment.

Integration of Activation by Hypoxia and Inhibition Resistance of Tumor Cells to Apoptosis for Precise and Augmented Photodynamic Therapy.

Photodynamic therapy (PDT) uses photosensitizers to convert oxygen (O2 ) to reactive oxygen species (ROS) under irradiation to induce DNA damage and kill cancer cells. However, the effect of PDT is usually alleviated by apoptosis resistance mechanism of tumor living cells. MTH1 enzyme is known to be such an apoptosis-resistance enzyme which is over expressed as a scavenger to repair the damaged DNA. In this work, a hypoxia-activated nanosystem FTPA, which can be degraded to release the encapsulated PDT photosensitizer 4-DCF-MPYM and an inhibitor TH588 is proposed. The inhibitor TH588 can inhibit the DNA repair process by reducing the activity of MTH1 enzyme, and achieve the purpose of amplifying the therapeutic effect of PDT. This work demonstrates that a precise and augmented tumor PDT is achieved by integration of hypoxia-activation and inhibition resistance of tumor cells to apoptosis.

A "Chase and Block" Strategy for Enhanced Cancer Therapy with Hypoxia-Promoted Photodynamic Therapy and Autophagy Inhibition Based on Upconversion Nanocomposites.

The combination of hypoxia-promoted photodynamic therapy (PDT) and autophagy modulation has shown strong potential in the treatment of hypoxic tumors. Here, a novel design is put forward for synergistic PDT and autophagy inhibition to amplify the effect of cancer therapy by a "chase and block" strategy. Specifically, the organic photosensitive molecule (denoted FL) is encapsulated in a hydrophobic layer between multi-band emitted upconversion nanoparticles (UCNPs) and the amphiphilic polymer DSPE-PEG-COOH, allowing FL to fully exploit the luminescence spectrum of UCNPs under near-infrared (NIR) light irradiation. The FL is specifically activated by nitroreductase in the tumor microenvironment (TME), enabling hypoxia-promoted PDT and thus performing a "chase" strategy for cancer therapy. Additionally, the nanosystem is combined with an autophagy-inhibiting melittin pro-peptide (denoted as MEL), which could be triggered by the highly expressed legumain in tumor cells to inhibit the autophagy procedure by disrupting the lysosomal membrane, thus "blocking" the cancer cells from rescuing themselves and amplifying the killing effect of PDT. Both FL and MEL can be specifically activated by TME and the upconversion luminescence imaging of UCNPs offers a tracer function for the treatment. Therefore, UCNPs@FL-MEL might be an important reference for the design and development of future nanotherapeutic agents.

Jointly Depleting Glutathione Based on Self-Assembled Nanomicelles for Enhancing Photodynamic Therapy.

Photodynamic therapy (PDT) is one common ROS-generating therapeutic method with high tumor selectivity and low side effects. But the GSH-upregulation often alleviates its therapeutic efficiency. Here, we proposed a new strategy of jointly depleting GSH to enhance the therapeutic effect of PDT by preparing a nanomicelle by self-assembly method from GSH-activated photosensitizer DMT, curcumin, and amphiphilic polymer TPGS.

[Clinical characteristics and genetic analysis of two children with Autosomal dominant mental retardation type 21 due to variants of CTCF gene].

OBJECTIVE: To explore the clinical and genetic characteristics of two children with developmental delay. METHODS: Two children who had presented at the Children's Hospital Affiliated to Shandong University on August 18, 2021 were enrolled as the study subjects. Clinical and laboratory examination, chromosomal karyotyping and high-throughput sequencing were carried out for both children. RESULTS: Both children had a 46,XX karyotype. High-throughput sequencing showed that they have respectively carried a c.489delG (p.Q165Rfs*14) and a c.1157_1158delAT (p.Y386Cfs*22) frameshifting variant of the CTCF gene, both had a de novo origin and were unreported previously. CONCLUSION: The CTCF gene variants probably underlay the development delay in the two children. Above discovery has enriched the mutational spectrum of the CTCF gene and has important implications for revealing the genotype-phenotype correlation for similar patients.

Integration of TADF Photosensitizer as "Electron Pump" and BSA as "Electron Reservoir" for Boosting Type I Photodynamic Therapy.

Type I photosensitization provides an effective solution to the problem of unsatisfactory photodynamic therapeutic (PDT) effects caused by the tumor hypoxia. The challenge in the development of Type I mode is to boost the photosensitizer's own electron transfer capacity. Herein, we found that the use of bovine serum albumin (BSA) to encapsulate a thermally activated delayed fluorescence (TADF) photosensitizer PS can significantly promote the Type I PDT process to generate a mass of superoxide anions (O2•-). This Type I photosensitization opened a new strategy by employing BSA as "electron reservoir" and TADF photosensitizer as "electron pump". We integrated these roles of BSA and PS in one system by preparing nanophotosensitizer PS@BSA. The Type I PDT performance was demonstrated with tumor cells under hypoxic conditions. Furthermore, PS@BSA took full advantage of the tumor-targeting role of BSA and achieved efficient PDT for tumor-bearing mice in the in vivo experiments. This work provides an effective route to improve the PDT efficiency of hypoxic tumors.

Poly(ionic liquid)s for Photo-Driven CO2 Cycloaddition: Electron Donor-Acceptor Segments Matter.

CO2 cycloaddition with epoxides is a key catalytic procedure for CO2 utilization. Several metal-based catalysts with cocatalysts are developed for photo-driven CO2 cycloaddition, while facing difficulties in product purification and continuous reaction. Here, poly(ionic liquid)s are proposed as metal-free catalysts for photo-driven CO2 cycloaddition without cocatalysts. A series of poly(ionic liquid)s with donor-acceptor segments are fabricated and their photo-driven catalytic performance (conversion rate of 83.5% for glycidyl phenyl ether) outstrips (≈4.9 times) their thermal-driven catalytic performance (17.2%) at the same temperature. Mechanism studies confirm that photo-induced charge separation is promoted by the donor-acceptor segments and can accelerate the CO2 cycloaddition reaction. This work paves the way for the further use of poly(ionic liquid)s as catalysts in photo-driven CO2 cycloaddition.

Boosting Type-I and Type-II ROS Production of Water-Soluble Porphyrin for Efficient Hypoxic Tumor Therapy.

As the most successful clinically approved photosensitizers, porphyrins have been extensively employed in the photodynamic therapy (PDT) of cancers. However, their poor water solubility, aggregation-induced self-quenching on ROS generation, and a low tolerance for a hypoxic condition usually result in unsatisfied therapeutic outcomes. Therefore, great efforts have been dedicated to improving the PDT efficacy of porphyrin-type photosensitizers in treating hypoxic tumors, including combination with additional active components or therapies, which can significantly complicate the therapeutic process. Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. We have also found that the end charges of side chains can dramatically affect the ROS generation of the porphyrin. The cationic porphyrin exhibited high in vitro PDT efficacy with low IC50 values both in normoxia and hypoxia. Hence, during in vivo PDT study, the cationic porphyrin displayed highly effective tumor ablation capability. This study demonstrates the power of side-chain chemistry in tuning the photodynamic property of porphyrin, which offers a new effective strategy to enhance the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics.

Genotypic and phenotypic characteristics of 12 chinese children with glycogen storage diseases.

Background: Glycogen storage diseases (GSDs) are known as a group of disorders characterized by genetic errors leading to accumulation of glycogen in various tissues. Since different types of GSD can sometimes be clinically indistinguishable, next generation sequencing is becoming a powerful tool for clinical diagnosis. Methods: 12 patients with suspected GSDs and their parents were enrolled in this study. The clinical and laboratory data of the patients were reviewed. Causative gene variants were identified in the patients using whole exome sequencing (WES) and verified by Sanger sequencing. Results: Genetic testing and analysis showed that 7 patients were diagnosed with GSD II (Pompe disease), 2 patients with GSD III, 1 patient with GSD VI, and 2 patients with GSD IXα. A total number of 18 variants were identified in 12 patients including 11 variants in GAA gene, 3 variants in AGL gene, 2 variants in PYGL gene and 2 variants in PHKA2 gene, of which 9 variants were reported and 9 variants were novel. SIFT, Polyphen-2, Mutation Taster, and REVEL predicted the novel variants (except GAA c.1052_1075 + 47del) to be disease-causing. The 3D structures of wild/mutant type GAA protein were predicted indicating that variants p. Trp621Gly, p. Pro541Leu, p. Ser800Ile and p. Gly293Trp might affect the proteins function via destroying hydrogen bonds or conformational constraints. Neither liver size nor laboratory findings allow for a differentiation among GSD III, GSD VI and GSD IXα. Conclusion: Our study expanded the variation spectrum of genes associated with GSDs. WES, in combination with clinical, biochemical, and pathological hallmarks, could provide accurate results for diagnosing and sub-typing GSD and related diseases in clinical setting.

A Selenium-Substituted Heptamethine Cyanine Photosensitizer for Near-Infrared Photodynamic Therapy.

Photodynamic therapy (PDT) is a relatively safe approach to cancer treatment without significant systemic side effects or drug resistance. However, the current PDT efficiency is unsatisfactory due to the lack of near-infrared (NIR) photosensitizers. Heptamethine cyanine (Cy7) dyes are well-known NIR fluorophores and are also used as photosensitizers. But their singlet oxygen quantum yields (ΦΔ ) are not ideal. Herein, we developed an NIR photosensitizer with a long-lived excited triplet state (τ=4.3 µs) by introducing a selenium atom into the structure of a Cy7 dye. The new NIR photosensitizer exhibits a significantly high singlet oxygen quantum yield (ΦΔ =0.11). Its good PDT effect was demonstrated in the living cells. Considering that the selenium-substituted photosensitizer has a very low dark cytotoxicity and good chemical stability, we conclude that it will have a promising future in biomedical and clinical applications.