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A major limitation of gene therapy for sickle cell disease (SCD) is the availability and access to a potentially curative one-time treatment, due to high treatment costs. We have developed a high-titer bifunctional lentiviral vector (LVV) in a vector backbone that has reduced size, high vector yields, and efficient gene transfer to human CD34+ hematopoietic stem and progenitor cells (HSPCs). This LVV contains locus control region cores expressing an anti-sickling βAS3-globin gene and two microRNA-adapted short hairpin RNA simultaneously targeting BCL11A and ZNF410 transcripts to maximally induce fetal hemoglobin (HbF) expression. This LVV induces high levels of anti-sickling hemoglobins (HbAAS3 + HbF), while concurrently decreasing sickle hemoglobin (HbS). The decrease in HbS and increased anti-sickling hemoglobin impedes deoxygenated HbS polymerization and red blood cell sickling at low vector copy per cell in transduced SCD patient CD34+ cells differentiated into erythrocytes. The dual alterations in red cell hemoglobins ameliorated the SCD phenotype in the SCD Berkeley mouse model in vivo. With high titer and enhanced transduction of HSPC at a low multiplicity of infection, this LVV will increase the number of patient doses of vector from production lots to decrease costs and help improve accessibility to gene therapy for SCD.

Molecular iron phthalocyanine (FePc) bearing a single‐atom Fe–N4 moiety is a high‐profile non‐platinum catalyst toward the oxygen reduction reaction (ORR), but its unsatisfactory activity and inadequate stability hinder the practical application. Herein, a novel strategy by hybridizing FePc with fullerene‐derived intrinsic defect‐rich carbon to improve its ORR activity and stability is reported. Via alkali‐assisted thermal pyrolysis, C60 molecules are disintegrated into tiny fragments that then restructure into pentagon‐ and edge‐rich carbon (FC). Utilizing FC as a support of FePc leads to a significantly improved ORR activity compared to other supports including reduced graphene oxide and carbon nanotube that hold distinct structural features. The optimized FePc/FC with a Fe loading of 3 wt% presents a half‐wave potential of 0.917 V, far beyond that of Pt/C (0.846 V), via selective four‐electron ORR pathway and excellent stability under accelerated stress test. The practical applicability of FePc/FC is also demonstrated as a high‐performing cathode catalyst of aqueous zinc–air batteries. It is, for the first time, explicitly disclosed that strong interactions between FePc molecules and intrinsic carbon defects (e.g., pentagons and edges) not only strengthen the anchoring effect of supported FePc but also enhance the intrinsic ORR activity of single‐atom Fe–N4 sites. [ABSTRACT FROM AUTHOR]

In this paper we study an inverse boundary value problem for the biharmonic operator with first order perturbation. Our geometric setting is that of a bounded simply connected domain in the Euclidean space of dimension three or higher. Assuming that the inaccessible portion of the boundary is flat, and we have knowledge of the Dirichlet-to-Neumann map on the complement, we prove logarithmic type stability estimates for both the first and the zeroth order perturbation of the biharmonic operator. [ABSTRACT FROM AUTHOR]

Rational design and synthesis of a unique heterojunction photocatalyst structure is an important strategy to enhance its performance and structural stability. Herein, Co 9 S 8 /MnCdS/Co 3 O 4 photocatalysts with double S-scheme heterojunctions were successfully prepared by coupling Co 9 S 8 and Co 3 O 4 sheet structures with n-type MnCdS nanoparticles through a simple solvothermal and mechanical mixing method. The construction of the dual S-scheme heterostructure offers the possibility to expand the light absorption range, extend the carrier lifetime and maximise the redox capacity. In addition, the mechanism of charge transfer and the reason for the improvement of photocatalytic activity were explored through photoelectrochemical characterization. The lamellar structures of Co 9 S 8 and Co 3 O 4 not only provide excellent dispersion and slow down the agglomeration of MnCdS nanoparticles, but also promote charge transfer, which improves the photocatalytic hydrogen production effect. Under simulated solar irradiation, the evolution rate of H 2 after 5 h was as high as 46.44 μmol, which was 3.49 and 1.49 times higher than those of pristine MnCdS and MnCdS/Co 3 O 4 , respectively. Meanwhile, it has good stability under 20 h irradiation. This work demonstrates a novel idea for the rational design of double S-scheme photocatalysts with efficient space separation.

This study analyzed the factors influencing childcare preference and the relationship between childcare preference and childcare service demand scale, using data collected from a questionnaire survey of 3,921 parents of infants and toddlers in Chongqing, China. The results indicate that parents with higher incomes, higher education levels, older ages, multiple infants, and dual-career living in urban areas have a stronger preference for childcare. In the shared or grandparent care model, the childcare preference is not obvious. Parents of infants tend to choose childcare institutions that provide reception services, early education, and convenience services. Higher quality environmental facilities tend to reduce the preference of parents for childcare., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Liu and Xu.)