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Over recent decades, bispecific antibodies (bsAbs) have garnered significant attention for their superior therapeutic efficacy compared to progenitor monoclonal antibodies, enabling innovative treatment strategies. Despite their potential, the development of bsAbs presents significant challenges, with structural stability playing a pivotal role in manufacturability, therapeutic performance, and safety. Among the factors influencing stability, the design and incorporation of molecular linkers are particularly critical. In this study, we investigated the structural stability and fragmentation profiles of a symmetric bispecific antibody (Sym-bsAb), targeting HER2 and CD3, under forced degradation conditions. The Sym-bsAb exhibited pronounced fragmentation under prolonged thermal stress, particularly when combined with high pH and salt conditions. Intact mass analysis identified key degradation events, including sequential clipping along G4S and G4 linkers, fragmentations at interchain cystinyl residues and cleavage at the C-terminal of asparagine residues. The identification of G4S and G4 linkers as vulnerable regions prone to clipping in Sym-bsAb provided valuable insights into the stability and manufacturability of bsAbs incorporating linker sequences, underscoring critical considerations for their development.

Background: B-cell maturation antigen (BCMA)-targeted T cell-redirecting immunotherapies, including Chimeric Antigen Receptor (CAR) T-cell therapy and T-cell engagers have demonstrated remarkable success in treating relapsed/refractory (RR) multiple myeloma (MM), a malignancy of plasma cells. However, a significant challenge is the severe side effects associated with T-cell overactivation, leading to cytokine release syndrome and neurotoxicity in MM patients undergoing such therapies. Bispecific NK cell engagers (NKCEs) may offer a promising alternative by redirecting NK cell cytotoxic activity towards tumor cells without triggering cytokine release syndrome. Methods: In this study, we designed a series of BCMA × CD16 NKCEs that simultaneously engage BCMA and CD16 on MM and NK cells, respectively. We evaluated the functionality of these NKCEs in vitro with respect to their molecular design. Results: Our results indicate that the format design of NKCEs influences their functionalities, underscoring the importance of format selection in optimizing NKCE-based therapies for MM. This study provides valuable insights for developing next-generation NKCEs and advancing therapeutic strategies for MM and potentially other malignancies.

Bispecific antibodies (bsAbs) hold promises for enhanced therapeutic potential surpassing that of their parental monoclonal antibodies. However, bsAbs pose great challenges in their manufacturing, and one of the common reasons is their susceptibility to aggregation. Building on previous studies demonstrating the functionality and potential manufacturability of Fab-scFv format bsAb, this investigation delved into the impact of environmental factors—such as pH, buffer types, ionic strength, protein concentrations, and temperatures—on its stability and the reversal of its self-associated aggregates. Mildly acidic, low-salt conditions were found optimal, ensuring bsAb stability for 30 days even at elevated temperature of 40 °C. Furthermore, these conditions facilitated the reversal of its self-associated aggregates to monomers during the initial 7-day incubation period. Our findings underscore the robustness and resilience of Fab-scFv format bsAb, further confirming its potential manufacturability despite its current absence as commercial products.

The genomes of Plasmodium spp . encode a number of different multigene families that are thought to play a critical role for survival. However, with the exception of the P. falciparum var genes, very little is known about the biological roles of any of the other multigene families. Using the recently developed Selection Linked Integration method, we have been able to activate the expression of a single member of a multigene family of our choice in Plasmodium spp . from its endogenous promoter. We demonstrate the usefulness of this approach by activating the expression of a unique var, rifin and stevor in P. falciparum as well as yir in P. yoelii . Characterization of the selected parasites reveals differences between the different families in terms of mutual exclusive control, co-regulation, and host adaptation. Our results further support the application of the approach for the study of multigene families in Plasmodium and other organisms. Omelianczyk, Loh et al. activate the expression of a single member of a multigene family in Plasmodium spp . from its endogenous promoter, identifying differences between the different families. This study supports the application of the Selection Linked Integration method for studying multigene families in Plasmodium .

We demonstrate that the intrinsic properties of monolayer graphene allow it to act as a more effective saturable absorber for mode-locking fiber lasers when compared to multilayer graphene. The absorption of monolayer graphene can be saturated at lower excitation intensity compared to multilayer graphene, graphene with wrinkle-like defects, or functionalized graphene. Monolayer graphene has a remarkably large modulation depth of 65.9%, whereas the modulation depth of multilayer graphene is greatly reduced due to nonsaturable absorption and scattering loss. Picosecond ultrafast laser pulses （1.23 ps） can be generated using monolayer graphene as a saturable absorber. Due to the ultrafast relaxation time, larger modulation depth and lower scattering loss of monolayer graphene, it performs better than multilayer graphene in terms of pulse shaping ability, pulse stability, and output energy.

Graphene oxide (GO) was initially developed to emulate graphene, but it was soon recognized as a functional material in its own right, addressing an application space that is not accessible to graphene and other carbon materials. Over the past decade, research on GO has made tremendous advances in material synthesis and property tailoring. These, in turn, have led to rapid progress in GO-based photonics, electronics and optoelectronics, paving the way for technological breakthroughs with exceptional performance. In this Review, we provide an overview of the optical, electrical and optoelectronic properties of GO and reduced GO on the basis of their chemical structures and fabrication approaches, together with their applications in key technologies such as solar energy harvesting, energy storage, medical diagnosis, image display and optical communications. We also discuss the challenges of this field, together with exciting opportunities for future technological advances. As the most common derivative of graphene, graphene oxide has emerged as a new frontier material with tremendous applications to photonics, electronics and optoelectronics in the past decade. This Review highlights the state of the art and future prospects for this fast-growing field.

Transition-metal dichalcogenides like molybdenum disulphide have attracted great interest as two-dimensional materials beyond graphene due to their unique electronic and optical properties. Solution-phase processes can be a viable method for producing printable single-layer chalcogenides. Molybdenum disulphide can be exfoliated into monolayer flakes using organolithium reduction chemistry; unfortunately, the method is hampered by low yield, submicron flake size and long lithiation time. Here we report a high-yield exfoliation process using lithium, potassium and sodium naphthalenide where an intermediate ternary Li x MX n crystalline phase (X=selenium, sulphur, and so on) is produced. Using a two-step expansion and intercalation method, we produce high-quality single-layer molybdenum disulphide sheets with unprecedentedly large flake size, that is up to 400 μm 2 . Single-layer dichalcogenide inks prepared by this method may be directly inkjet-printed on a wide range of substrates. Molybdenum disulphide may be prepared by lithiation and exfoliation; however the process requires a long lithiation and produces low yields. Here, the authors show that metal naphthalenides may be used for the intercalation, and that the resulting products are of high quality and may be inkjet-printed.

Precisely controlled deuterium labeling at specific sites of N -alkyl drugs is crucial in drug-development as over 50% of the top-selling drugs contain N -alkyl groups, in which it is very challenging to selectively replace protons with deuterium atoms. With the goal of achieving controllable isotope-labeling in N -alkylated amines, we herein rationally design photocatalytic water-splitting to furnish [H] or [D] and isotope alkanol-oxidation by photoexcited electron-hole pairs on a polymeric semiconductor. The controlled installation of N -CH 3, -CDH 2, -CD 2 H, -CD 3 , and - 13 CH 3 groups into pharmaceutical amines thus has been demonstrated by tuning isotopic water and methanol. More than 50 examples with a wide range of functionalities are presented, demonstrating the universal applicability and mildness of this strategy. Gram-scale production has been realized, paving the way for the practical photosynthesis of pharmaceuticals. Controllable deuteration of N-alkyl amines is crucial in drug-development as they constitute over 50% of the top-selling drugs. Here, the authors report a polymeric semiconductor acting as photocatalyst in water-splitting and in isotope alkanol-oxidation by photoexcited electron-hole pairs, and furnishing deuterated amines.

The spin Hall effect (SHE) is usually observed as a bulk effect in high-symmetry crystals with substantial spin–orbit coupling (SOC), where the symmetric spin–orbit field imposes a widely encountered trade-off between spin Hall angle ( θ SH ) and spin diffusion length ( L sf ), and spin polarization, spin current and charge current are constrained to be mutually orthogonal. Here, we report a large θ SH of 0.32 accompanied by a long L sf of 2.2 μm at room temperature in a low-symmetry few-layered semimetal MoTe 2 , thus identifying it as an excellent candidate for simultaneous spin generation, transport and detection. In addition, we report that longitudinal spin current with out-of-plane polarization can be generated by both transverse and vertical charge current, due to the conventional and a newly observed planar SHE, respectively. Our study suggests that manipulation of crystalline symmetries and strong SOC opens access to new charge-spin interconversion configurations and spin–orbit torques for spintronic applications. A large spin Hall angle and long spin diffusion length are found in the low-symmetry, few-layer semimetal MoTe 2 at room temperature, thus identifying this material as an excellent candidate for simultaneous spin generation, transport and detection.

Oct4 and Nanog are transcription factors required to maintain the pluripotency and self-renewal of embryonic stem (ES) cells. Using the chromatin immunoprecipitation paired-end ditags method, we mapped the binding sites of these factors in the mouse ES cell genome. We identified 1,083 and 3,006 high-confidence binding sites for Oct4 and Nanog, respectively. Comparative location analyses indicated that Oct4 and Nanog overlap substantially in their targets, and they are bound to genes in different configurations. Using de novo motif discovery algorithms, we defined the cis -acting elements mediating their respective binding to genomic sites. By integrating RNA interference–mediated depletion of Oct4 and Nanog with microarray expression profiling, we demonstrated that these factors can activate or suppress transcription. We further showed that common core downstream targets are important to keep ES cells from differentiating. The emerging picture is one in which Oct4 and Nanog control a cascade of pathways that are intricately connected to govern pluripotency, self-renewal, genome surveillance and cell fate determination.