Negative photoconductivity in low-dimensional materials

In recent years,low-dimensional materials have received extensive attention in the field of electronics and optoelectronics.Among them,photoelectric devices based on photoconductive effect in low-dimensional materials have a broad development space.In contrast to positive photoconductivity,negative photoconductivity(NPC)refers to a phenomenon that the conductivity decreases under illumination.It has novel application prospects in the field of optoelectronics,memory,and gas detection,etc.In this paper,we review reports about the NPC effect in low-dimensional materials and systematically summarize the mechanisms to form the NPC effect in existing low-dimensional materials.

Spin orbit torques in Pt-based heterostructures with van der Waals interface

Spin orbit torques(SOTs)in ferromagnet/heavy-metal heterostructures have provided great opportunities for efficient manipulation of spintronic devices.However,deterministically field-free switching of perpendicular magnetization with SOTs is forbidden because of the global two-fold rotational symmetry in conventional heavy-metal such as Pt.Here,we engineer the interface of Pt/Ni heterostructures by inserting a monolayer MoTe_(2)with low crystal symmetry.It is demonstrated that the spin orbit efficiency,as well as the out-of-plane magnetic anisotropy and the Gilbert damping of Ni are enhanced,due to the effect of orbital hybridization and the increased spin scatting at the interface induced by MoTe_(2).Particularly,an out-of-plane damping-like torque is observed when the current is applied perpendicular to the mirror plane of the MoTe_(2)crystal,which is attributed to the interfacial inversion symmetry breaking of the system.Our work provides an effective route for engineering the SOT in Pt-based heterostructures,and offers potential opportunities for van der Waals interfaces in spintronic devices.

Microfluidic one-step, aqueous synthesis of size-tunable zeolitic imidazolate framework-8 for protein delivery

Zeolitic imidazolate framework-8(ZIF-8)with porous structure,biocompatibility,and pH-sensitive release behavior is a promising nanoplatform for protein delivery.However,it is still a challenging task for a practical synthesis of protein-loaded ZIF-8 nanoparticles.Here we report an all-aqueous microfluidic reactor for one-step,rapid,and highly controlled synthesis of ZIF-8 nanoparticles with high protein loading at room temperature.Microfluidic reactor allows for an ultrafast(<35 ms),complete mixing of Zn2+ions and 2-methylimidazole(2-MIM)at different molecular ratios,leading to the formation of stable ZIF-8 nanoparticles with tunable sizes(13.2–191.4 nm)in less than 30 s.By pre-mixing various proteins such as bovine serum albumin(BSA)(isoelectric point(pI)=5.82),ovalbumin(OVA)(pI=4.82),or RNase A(pI=8.93)with 2-MIM,ZIF-8 nanoparticles can be synthesized with protein encapsulation efficiency over 97%.Among the nanoparticles with different sizes,25 nm ZIF-8 nanoparticles show the best performance in promoting the cellular uptake of protein payload.Using OVA as a model protein,we demonstrate that 25 nm ZIF-8 nanoparticles significantly enhance the cytosolic delivery of antigen,as indicated by the effective activation of dendritic cells.We anticipate that this microfluidic synthesis of nanomaterials may advance the emerging field of cytosolic protein delivery.

Developing potent BTK^(C481S)PROTACs for ibrutinib-resistant malignant lymphoma

Ibrutinib is a first-line treatment drug for B-cell malignancies.However,resistance to ibrutinib has been reported due to BTKC481Smutation.Although PROTAC strategy is expected to overcome this clinical resistance,it has limitations such as large molecular weight and moderate bioactivity,which restrict its potential clinical application.Herein,we report a new type of potent BTKC481S-targeting PROTAC degrader.Through design,computer-assisted optimization and SAR studies,we have developed a representative BTKC481Sdegrader L6 with a much smaller molecular weight and improved solubility.Notably,L6 demonstrates better BTK degrading activity and lower IC50value in ibrutinib-resistant cell line than the first-generation BTK degrader P13I.Optimization strategy of L6 provides a general approach in the development of PROTACs targeting BTK and other proteins for future study.

Developing potent PROTACs tools for selective degradation of HDAC6 protein

Dear Editor, Histone deacetylases (HDACs) are a family of enzymes that remove acetyl groups on histone and non-histone proteins, thereby playing a vital role in the modulation of gene expression and protein activity. Eighteen HDACs have been identified in human and subdivided into four classes including I, II (Ila, lib), III and IV (Seto et al., 2014). Among them, HDAC6 is a unique lib HD AC with dominant cytoplasmic localization and two functional catalytic domains. Besides the functions for deacetylation of histone, and modulation of a-tubulin, HSP90 and cortactin, HDAC6 also participates in protein trafficking and degradation, cell shape and migration (Valenzuela-Fernandez et al., 2008). The deregulation of HDAC6 is related to various diseases, such as neurodegenerative diseases, cancer and pathological autoimmune response (Batchu et al., 2016). Hence, it is especially important for directly controlling cellular HDAC6 protein levels to achieve therapeutic purposes. The traditional approaches of red u ci ng cellular protein levels mainly rely on genetic modifications, such as RNA interference, transcription activator-like effector nucleases, recombination-based gene knockout and clustered regularly interspaced short palindromic repeats (CRISPR-Cas9)(Boettcher et al., 2015). However, these approaches have failed to a certain degree to achieve acute and reversible changes of gene function. Furthermore, the complications of potential genetic compensation and/or spontaneous mutations arising in geneknockout models may lead to misinterpretations (Davisson etal., 2012;El-Brolosy etal., 2017). Therefore, it is urgent for developing a rapid, robust, and reversible approach to directly modulate HDAC6 protein levels.

Correction to: Developing potent PROTACs tools for selective degradation of HDAC6 protein

In the original publication the title of X axis in Fig.1G is in correctly published as"Compound(pmol/L)".The correct title of X axis in Fig.1G should be read as"Compound(nmol/L)M.Figure 1.Development of selective HDAC6-degrading PROTACs.(A)The principle of PROTAC.(B)The structure of PROTAC,as shown in the upper portion.A binding mode of PROTAC(ball stick),HDAC6(PDB 5G0J,purple)and CRL4-CRBN(PDB 2HYE and 4CI3,colored cyan and gray)was simulated by Pymol.

Exosome-Coated Zeolitic Imidazolate Framework Nanoparticles for Intracellular Detection of ATP

The intracellular delivery of metal-organic frameworks(MOFs)encapsulated with functional biomolecules represents a promising av-enue in the field of biomedicine and biosensing.To improve the cellular uptake efficiency of MOFs,here we report the fabrication of cancer cell-derived exosome membra ne(EM)-coated zeolitic imidazolate framework-8(EM-ZIF-8)nan oparticles by using a microfluidic son ication device.