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Background: Familial hypercholesterolemia (FH) is a common monogenic autosomal dominant disorder, primarily mainly caused by pathogenic mutations in the low-density lipoprotein receptor (LDLR) gene. Through phenotypic-genetic linkage analysis, two LDLR pathogenic mutations were identified in FH families: c.G1027A (p.Gly343Ser) and c.G1879A (p.Ala627Thr). Materials and methods: Whole exome sequencing was conducted on the proband with familial hypercholesterolemia to identify the target gene and screen for potential pathogenic mutations. The suspicious responsible mutation sites in 14 family members were analyzed using Sanger sequencing to assess genotype-phenotype correlations. Mutant and wild type plasmids were constructed and transfected into HEK293T cells to evaluate LDLR mRNA and protein expression. In parallel, bioinformatics tools were employed to predict structural and functional changes in the mutant LDLR. Results: Immunofluorescence analysis revealed no significant difference in the intracellular localization of the p.Gly343Ser mutation, whereas protein expression of the p.Ala627Thr mutation was decreased and predominantly localized in the cytoplasm. Western blotting has showed that protein expression levels of the mutant variants were markedly declined in both cell lysates and supernatants. Enzyme linked immunosorbent assay has demonstrated that LDLR protein levels in the supernatant of cell culture medium was not significant different from those of the wild-type group. However, LDLR protein levels in the cell lysate of both the Gly343Ser and Ala627Thr variants groups were significantly lower than those in the wild-type group. Bioinformatic predictions further suggested that these mutations may affect post-translational modifications of the protein, providing additional insight into the mechanisms underlying the observed reduction in protein expression. Conclusions: In this study, we identified two heterozygous pathogenic variants in the LDLR gene, c.G1027A (p.Gly343Ser) and c.G1879A (p.Ala627Thr), in a family with familial hypercholesterolemia. We also conducted preliminary investigations into the mechanisms by which these mutations contribute to disease pathology. [ABSTRACT FROM AUTHOR]

In order to investigate the influence of cutwater on the hydraulic performance of the pump as a turbine (PAT) and improve the performance of the pump operated in reverse as a turbine, a single-stage single-suction centrifugal pump with a specific speed of 69 was selected as the research object. Nine schemes, including the original model, with variations in cutwater placement angle and cutwater radius, were designed. Using the SST k-ω model, numerical simulations of the entire flow passage were conducted for each scheme. Entropy production diagnostic analysis was introduced to analyze the variations in head, efficiency, and internal flow field of the PAT under different schemes. The research results show that within a certain range, increasing the cutwater placement angle leads to a significant reduction in head of the hydraulic PAT in the larger flow rate range. In this PAT, when the cutwater radius is 1.5 mm, the entropy production loss inside the impeller and volute is reduced, resulting in an increase in PAT efficiency. [ABSTRACT FROM AUTHOR]

Multiresonant thermally activated delayed fluorescence (MR-TADF) compounds are attractive for use in organic light-emitting diodes as they show narrowband emission, are bright, and can harvest both singlet and triplet excitons for the emission of light. Reflected in the paucity of examples of orange-to-red emitters, developing MR-TADF emitters that emit beyond the green remains an outstanding materials design challenge. In this work, we report one of the first carbonyl-based orange MR-TADF emitters, DDiKTa-A, which is based on the dimerization of the sky-blue emitting DiKTa through a central aniline bridge. DDiKTa-A emits at λPL of 562 nm and has high photoluminescence quantum yield of 92% in 2 wt% doped films in mCP. DDiKTa-A exhibits temperature dependent steady-state photoluminescence in 2-MeTHF, acting as an indirect indicator of the polarity of the medium. The OLEDs with DDiKTa-A showed an EQEmax of 20.3%, but with significant efficiency roll-off (EQE100 of 13.2%). The EQEmax was improved, and the efficiency roll-off mitigated by incorporating an assistant dopant, 4CzIPN, within the emissive layer of the device. The hyperfluorescence device showed an EQEmax of 24.3%, which decreased to 22.5 and 14.6% at 100 and 1000 cd m−2, respectively. [ABSTRACT FROM AUTHOR]

Herein, we report a fluorene-bridged double carbonyl/amine-based MR TADF emitter DDiKTa-F, formed by locking the conformation of the previously reported compound DDiKTa. Using this strategy, DDiKTa-F exhibited narrower, brighter, and red-shifted emission. The OLEDs with DDiKTa-F emitted at 493 nm and showed an EQEmax of 15.3% with an efficiency roll-off of 35% at 100 cd m−2. [ABSTRACT FROM AUTHOR]

Background: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare autoimmune disease characterized by skin or osteoarticular damage. SAPHO syndrome is often misdiagnosed or missed diagnosis due to lack of overall understanding of the disease by clinicians. Purpose: To analyze the clinical symptoms and imaging features of six Han patients with SAPHO syndrome in order to provide reference for doctors to diagnose SAPHO syndrome. Material and Methods: This study retrospectively analyzed the clinical data of six Han patients with SAPHO syndrome. Results: All six Han patients with SAPHO syndrome had severe acne or pustulosis of the hands and feet, and all of them had osteoarticular damage, including five cases involving the sternoclavicular joint. Some patients showed a specific and typical "bull's head" sign on 99mTc-labeled methylene diphosphonate bone imaging. Among the six patients recruited, there was one thoracic vertebra, one cervical vertebra, one sacroiliac joint, and one peripheral joint involvement. Two patients had limited activity due to severe osteoarticular damage. Conclusion: Due to the atypical clinical symptoms of SAPHO syndrome, most patients will experience a tortuous and long diagnostic process, while a correct understanding and timely intervention of SAPHO syndrome are essential to improve the prognosis of patients. [ABSTRACT FROM AUTHOR]

Nitrogen-containing polycyclic aromatic hydrocarbons (N-PAH) have been widely used as deep lowest unoccupied molecular orbital (LUMO) acceptors in donor–acceptor (D–A) red thermally activated delayed fluorescence (TADF) emitters and in organic light-emitting diodes (OLEDs). However, most of the studies have focused disparately on donor/acceptor combinations to yield efficient emitters, while a methodological study investigating the influence of nitrogen (N) doping ratios on the ground and excited states of PAH acceptors is rare. Here, we report a family of four different N-PAH acceptors containing different numbers of nitrogen atoms within the N-PAH and their use in D–A TADF emitters, DMACBP, DMACPyBP, DMACBPN and DMACPyBPN, when coupled to the same donor, 9,9-dimethyl-9,10-dihydroacridine (DMAC). As the nitrogen content in the acceptor increases the LUMO becomes progressively more stabilized while the singlet–triplet energy gap (ΔEST) decreases and the rate constant for reverse intersystem crossing (kRISC) increases. In particular, introducing nitrogen at the 10-position of dibenzo[a,c]phenazine (BP) leads to a more than ten-fold enhancement in kRISC in DMACPyBP and DMACPyBPN compared to DMACBP and DMACBPN. Among the OLEDs with all four emitters that with DMACBPN demonstrates the highest EQEmax of 19.4% at an emission peak of 588 nm, while the deepest red emitting device employed DMACPyBPN (λEL = 640 nm) with an EQEmax of 5.4%. [ABSTRACT FROM AUTHOR]

Realizing blue‐hazard‐free emission is an important goal for white organic light‐emitting diodes (OLEDs) toward healthy lighting applications. However, conventional blue organic emitters with broad emission spectra would generally cover the high‐energy emission region and thus cannot meet the demand. Here a blue multiple resonance type thermally activated delayed fluorescence (TADF) emitter DPMX‐CzDABNA is newly designed. The DPMX‐CzDABNA‐based OLEDs can realize blue narrowband emission peaked at 484 nm with a full width at half maximum of 29 nm, and external quantum efficiencies (EQEs) around 26%, which allows DPMX‐CzDABNA to precisely avoid the high‐energy photon contribution and thus be a promising blue component to construct high‐performance white OLEDs with human‐eye‐friendly emission spectra. Using DPMX‐CzDABNA and a reported TADF emitter BPPZ‐DPXZ, respectively, as blue and orange components in white OLEDs, the single‐emitting‐layer devices approach white emission with outstanding EQE up to 35.8%; the double‐emitting‐layer OLEDs achieve blue‐hazard‐free white emissions with a maximum EQE of 26.5% and very stable Commission Internationale de l'Eclairage coordinates of ≈(0.38,0.43) over a wide luminance range from 100 to 10 000 cd m−2. It is expected that this strategy can pave a new way for developing highly efficient all‐TADF white OLEDs without blue‐hazard emission. [ABSTRACT FROM AUTHOR]

Background: Hereditary factor VII deficiency (FVIID) is a rare congenital autosomal recessive bleeding disorder. In clinical manifestations, its onset is caused by variant of the F7 gene (NM_019616) with strong heterogeneity. We identified a family with hematuria caused by a novel F7 compound heterozygous variant and investigated the FVIID‐dependent mechanism impacted by these variants. Methods: Coagulation factors in the proband were functionally verified. We located pathogenic variants in relevant genes using next‐generation sequencing after target enrichment and verified them by Sanger sequencing. We examined the coagulation activity and secretion pattern of recombinant FVII variants expressed in cells and observed their location and stability by immunofluorescence. Results: We found a missense variant c.1207G>A (p.Gly403Ser) and a frameshift variant c.154_155del (p.Arg53fs) in the F7 gene of the proband. FVII activity tests showed that the variants significantly decreased its presence in the cell culture supernatant. Moreover, the R53fs mutant lacked the FVII functional domain and had no detectable activity. Immunofluorescence indicated that the p.Gly403Ser variant was distributed to the cell membrane and cytoplasm, whereas the FVII R53fs variant was not detected. Deficient FVII protein function and severe coagulation disorder are the likely causes of hematuria and other bleeding symptoms in the proband. Conclusions: The newly discovered F7 gene variants enrich the spectrum of hereditary FVII deficiency and provide a new foundation for the diagnosis and treatment of this type of coagulation disorder. [ABSTRACT FROM AUTHOR]

Thermally activated delayed fluorescence (TADF) emitters induced by the multiple resonance (MR) effect have garnered considerable attention. However, it is difficult to develop MR‐TADF emitters that maintain high color purities in the red region. In this work, the importance of excited state alignments of MR‐based donor‐acceptor (D‐A) molecules in determining their preferring characteristics is clarified. By using the newly designed molecule mBDPA‐TOAT whose apparent excited states show hybridization of MR and intersegmental charge‐transfer features as an emitter in an organic light‐emitting diode (OLED), a high external quantum efficiency of 17.3% is achieved with a full width at half‐maximum of 45 nm (154 meV) and Commission Internationale de L'Éclairage coordinate of (0.61, 0.39). This work demonstrates when introducing D‐A typed structures, features, and alignments of molecular excited states determine ultimate material properties. This could help to develop high efficiency and high color purity TADF emitters toward long wavelength range. [ABSTRACT FROM AUTHOR]