DNA topology regulates PAM-Cas9 interaction and DNA unwinding to enable near-PAMless cleavage by thermophilic Cas9.

CRISPR-Cas9-mediated genome editing depends on PAM recognition to initiate DNA unwinding. PAM mutations can abolish Cas9 binding and prohibit editing. Here, we identified a Cas9 from the thermophile Alicyclobacillus tengchongensis for which the PAM interaction can be robustly regulated by DNA topology. AtCas9 has a relaxed PAM of N4CNNN and N4RNNA (R = A/G) and is able to bind but not cleave targets with mutated PAMs. When PAM-mutated DNA was in underwound topology, AtCas9 exhibited enhanced binding affinity and high cleavage activity. Mechanistically, AtCas9 has a unique loop motif, which docked into the DNA major groove, and this interaction can be regulated by DNA topology. More importantly, AtCas9 showed near-PAMless editing of supercoiled plasmid in E. coli. In mammalian cells, AtCas9 exhibited broad PAM preference to edit plasmid with up to 72% efficiency and effective base editing at four endogenous loci, representing a potentially powerful tool for near-PAMless editing.

Tumor Microenvironment-Induced Drug Depository for Persistent Antitumor Chemotherapy and Immune Activation.

Herein, a drug-loading nanosystem that can in situ form drug depository for persistent antitumor chemotherapy and immune regulation is designed and built. The system (DOX@MIL-LOX@AL) is fabricated by packaging alginate on the surface of Doxorubicin (DOX) and lactate oxidase (LOX) loaded MIL-101(Fe)-NH2 nanoparticle, which can easily aggregate in the tumor microenvironment through the cross-linking with intratumoral Ca2+. Benefiting from the tumor retention ability, the fast-formed drug depository will continuously release DOX and Fe ions through the ATP-triggered slow degradation, thus realizing persistent antitumor chemotherapy and immune regulation. Meanwhile, LOX in the non-aggregated nanoparticles is able to convert the lactic acid to H2O2, which will be subsequently decomposed into ·OH by Fe ions to further enhance the DOX-induced immunogenic death effect of tumor cells. Together, with the effective consumption of immunosuppressive lactic acid, long-term chemotherapy, and oxidation therapy, DOX@MIL-LOX@AL can execute high-performance antitumor chemotherapy and immune activation with only one subcutaneous administration.

MXene hydrogels: fundamentals and applications.

Hydrogels have recently garnered tremendous interest due to their potential application in soft electronics, human-machine interfaces, sensors, actuators, and flexible energy storage. Benefiting from their impressive combination of hydrophilicity, metallic conductivity, high aspect ratio morphology, and widely tuneable properties, when two-dimensional (2D) transition metal carbides/nitrides (MXenes) are incorporated into hydrogel systems, they offer exciting and versatile platforms for the design of MXene-based soft materials with tunable application-specific properties. The intriguing and, in some cases, unique properties of MXene hydrogels are governed by complex gel structures and gelation mechanisms, which require in-depth investigation and engineering at the nanoscale. On the other hand, the formulation of MXenes into hydrogels can significantly increase the stability of MXenes, which is often the limiting factor for many MXene-based applications. Moreover, through simple treatments, derivatives of MXene hydrogels, such as aerogels, can be obtained, further expanding their versatility. This tutorial review intends to show the enormous potential of MXene hydrogels in expanding the application range of both hydrogels and MXenes, as well as increasing the performance of MXene-based devices. We elucidate the existing structures of various MXene-containing hydrogel systems along with their gelation mechanisms and the interconnecting driving forces. We then discuss their distinctive properties stemming from the integration of MXenes into hydrogels, which have revealed an enhanced performance, compared to either MXenes or hydrogels alone, in many applications (energy storage/harvesting, biomedicine, catalysis, electromagnetic interference shielding, and sensing).

Asymmetric Catalytic [4+5] Annulation of ortho-Quinone Methides with Vinylethylene Carbonates and its Extension to Stereoselective Tandem Rearrangement.

Palladium-catalyzed asymmetric [4+5] annulation of ortho-quinone methides (o-QMs) with substituted vinylethylene carbonates (VECs) is described for the first time, giving a novel enantioselective approach to chiral nine-membered benzoheterocycles. Based on this designed [4+5] annulation, an unprecedented silica gel-promoted tandem rearrangement reaction featuring a unique asymmetric aromatic Claisen rearrangement is explored at room temperature, offering a new method for asymmetric construction of all-carbon quaternary stereocenters embedded in chiral functionalized homoallylic alcohols.

Printed supercapacitors: materials, printing and applications.

Supercapacitors hold great promise for future electronic systems that are moving towards being flexible, portable, and highly integrated, due to their superior power density, stability and cycle lives. Printed electronics represents a paradigm shift in the manufacturing of supercapacitors in that it provides a whole range of simple, low-cost, time-saving, versatile and environmentally-friendly manufacturing technologies for supercapacitors with new and desirable structures (micro-, asymmetric, flexible, etc.), thus unleashing the full potential of supercapacitors for future electronics. In this review, we start by introducing the structural features of printed supercapacitors, followed by a summary of materials related to printed supercapacitors, including electrodes, electrolytes, current collectors and substrates; then the approaches to improve the performance of printed supercapacitors by tuning printing processes are discussed; next a summary of the recent developments of printed supercapacitors is given in terms of specific printing methods utilized; finally, challenges and future research opportunities of this exciting research direction are presented.

Inkjet-Printed High-Performance Flexible Micro-Supercapacitors with Porous Nanofiber-Like Electrode Structures.

Flexible planar micro-supercapacitors (MSCs) with unique loose and porous nanofiber-like electrode structures are fabricated by combining electrochemical deposition with inkjet printing. Benefiting from the resulting porous nanofiber-like structures, the areal capacitance of the inkjet-printed flexible planar MSCs is obviously enhanced to 46.6 mF cm-2 , which is among the highest values ever reported for MSCs. The complicated fabrication process is successfully averted as compared with previously reported best-performing planar MSCs. Besides excellent electrochemical performance, the resultant MSCs also show superior mechanical flexibility. The as-fabricated MSCs can be highly bent to 180° 1000 times with the capacitance retention still up to 86.8%. Intriguingly, because of the remarkable patterning capability of inkjet printing, various modular MSCs in serial and in parallel can be directly and facilely inkjet-printed without using external metal interconnects and tedious procedures. As a consequence, the electrochemical performance can be largely enhanced to better meet the demands of practical applications. Additionally, flexible serial MSCs with exquisite and aesthetic patterns are also inkjet-printed, showing great potential in fashionable wearable electronics. The results suggest a feasible strategy for the facile and cost-effective fabrication of high-performance flexible MSCs via inkjet printing.

Flexible supercapacitors based on paper substrates: a new paradigm for low-cost energy storage.

Paper-based supercapacitors (SCs), a novel and interesting group of flexible energy storage devices, are attracting more and more attention from both industry and academia. Cellulose papers with a unique porous bulk structure and rough and absorptive surface properties enable the construction of paper-based SCs with a reasonably good performance at a low price. The inexpensive and environmentally friendly nature of paper as well as simple fabrication techniques make paper-based SCs promising candidates for the future 'green' and 'once-use-and-throw-away' electronics. This review introduces the design, fabrication and applications of paper-based SCs, giving a comprehensive coverage of this interesting field. Challenges and future perspectives are also discussed.

Nanoplatform-based strategies for enhancing the lethality of current antitumor PDT.

Photodynamic therapy (PDT) exhibits great application prospects in future clinical oncology due to its spatiotemporal controllability and good biosafety. However, the antitumor efficacy of PDT is seriously hindered by many factors, including tumor hypoxia, limited light penetration ability, and strong defense mechanisms of tumors. Considering that it is difficult to completely solve the first two problems, enhancing the lethality of antitumor PDT has become a good idea to extend its clinical application. Herein, we summarize the nanoplatform-involved strategies to effectively amplify the tumoricidal capability of current PDT and then discuss the present bottlenecks and prospects of the nanoplatform-based PDT sensitization strategies in tumor therapy. We hope this review will provide some references for others to design high-performance PDT nanoplatforms for tumor therapy.

Ningxin-Tongyu-Zishen formula alleviates the senescence of granulosa cells on D-galactose-induced premature ovarian insufficiency mice.

Ningxin-Tongyu-Zishen formula (NTZF) is a clinical experience formula for the treatment of premature ovarian insufficiency (POI) in traditional Chinese medicine (TCM), and the potential mechanism is unknown. For in vivo experiments, POI mouse models (C57BL/6 mice), were constructed by subcutaneous injection of D-galactose (D-gal, 200 mg/kg). After treatment of NTZF (10.14, 20.27, 40.54 g/kg;) or estradiol valerate (0.15 mg/kg), ovarian function, oxidative stress (OS) and protein expression of Sirt1/p53 were evaluated. For in vitro experiments, H2O2 (200 µM) was used to treat KGN to construct ovarian granulosa cells (OGCs) cell senescence model. Pretreatment with NTZF (1.06 mg/mL) or p53 inhibitor (Pifithrin-α, 1 µM) was performed before induction of senescence, and further evaluated the cell senescence, OS, mRNA and protein expression of Sirt1/p53. In vivo, NTZF improved ovarian function, alleviated OS and Sirt1/p53 signaling abnormalities in POI mice. In vitro experiments showed that NTZF reduced the level of OS and alleviated the senescence of H2O2-induced KGN. In addition, NTZF activated the protein expression of Sirt1, inhibited the mRNA transcription and protein expression of p53 and p21. Alleviating OGCs senescence and protecting ovarian function through Sirt1/p53 is one of the potential mechanisms of NTZF in the treatment of POI.

Gel Electrolytes: Chemistry and Applications.

This Special Collection highlights the latest developments in the field of gel electrolytes. In this Editorial, guest editors Haitao Zhang, Du Yuan, Jin Zhao, Xiaoyan Ji, and Yi-Zhou Zhang briefly introduced the research focusing on chemistry and applications of gel electrolytes in this special collection.

MXene-Based Functional Platforms for Tumor Therapy.

Recently, 2D transition metal carbide, nitride, and carbonitrides (MXenes) materials stand out in the field of tumor therapy, particularly in the construction of functional platforms for optimal antitumor therapy due to their high specific surface area, tunable performance, strong absorption of near-infrared light as well as preferable surface plasmon resonance effect. In this review, the progress of MXene-mediated antitumor therapy is summarized after appropriate modifications or integration procedures. The enhanced antitumor treatments directly performed by MXenes, the significant improving effect of MXenes on different antitumor therapies, as well as the MXene-mediated imaging-guided antitumor strategies are discussed in detail. Moreover, the existing challenges and future development directions of MXenes in tumor therapy are presented.

Base editing of the HBG promoter induces potent fetal hemoglobin expression with no detectable off-target mutations in human HSCs.

Reactivating silenced γ-globin expression through the disruption of repressive regulatory domains offers a therapeutic strategy for treating ß-hemoglobinopathies. Here, we used transformer base editor (tBE), a recently developed cytosine base editor with no detectable off-target mutations, to disrupt transcription-factor-binding motifs in hematopoietic stem cells. By performing functional screening of six motifs with tBE, we found that directly disrupting the BCL11A-binding motif in HBG1/2 promoters triggered the highest γ-globin expression. Via a side-by-side comparison with other clinical and preclinical strategies using Cas9 nuclease or conventional BEs (ABE8e and hA3A-BE3), we found that tBE-mediated disruption of the BCL11A-binding motif at the HBG1/2 promoters triggered the highest fetal hemoglobin in healthy and ß-thalassemia patient hematopoietic stem/progenitor cells while exhibiting no detectable DNA or RNA off-target mutations. Durable therapeutic editing by tBE persisted in repopulating hematopoietic stem cells, demonstrating that tBE-mediated editing in HBG1/2 promoters is a safe and effective strategy for treating ß-hemoglobinopathies.

MXenes for Energy Harvesting.

Energy harvesting modules play an increasingly important role in the development of autonomous self-powered microelectronic devices. MXenes (i.e., 2D transition metal carbide/nitride) have recently emerged as promising candidates for energy applications due to their excellent electronic conductivity, large specific surface area, and tunable properties. Herein, a perspective on using MXenes to harvest energy from various sources in the environment is presented. First, the characteristics of MXenes that facilitate energy capturing are systematically introduced and the preparation strategies of MXenes and their derived nanostructures tailored toward such applications are summarized. Subsequently, the harvesting mechanism of different energy sources (e.g., solar energy, thermoelectric energy, triboelectric energy, piezoelectric energy, salinity-gradient energy, electrokinetic energy, ultrasound energy, and humidity energy) are discussed. Then, the recent progress of MXene-based nanostructures in energy harvesting, as well as their applications, is introduced. Finally, opinions on the existing challenges and future directions of MXene-based nanostructure for energy harvesting are presented.

Wireless Human-Machine Interface Based on Artificial Bionic Skin with Damage Reconfiguration and Multisensing Capabilities.

Human-machine interfaces (HMIs) enable users to interact with machines, thus playing a significant role in artificial intelligence, virtual reality, and the metaverse. Conventional HMIs are based on bulky and rigid electronic devices, seriously limiting their ductility, damage reconfiguration, and multifunctionality. In terms of replacing conventional HMIs, artificial bionic skins with good ductility, self-reparation, and multisensory ability are promising candidates. Still, they in their present form require innovations in mechanical and sensory properties, especially damage recovery and environmental stability, which seriously affect the service life and result in tons of electric waste. Herein, we present a new type of artificial bionic skin with excellent mechanical performance (>13,000% strain), high environmental stability (-80 to 80 °C), and multiple sensory properties toward strain, stress, temperature, solvent, and bioelectricity. Besides, this new type of artificial bionic skin also exhibits effective reconfiguration ability after damage and recyclability. The as-prepared artificial bionic skin was used as an interactive HMI to collect and distinguish the different sensory stimuli. The electronics assembled by HMI with artificial bionic skin can adhere compliantly on the human body for wireless motion capturing and sensing via Bluetooth, Wi-Fi, and the Internet. With simple programming, complex human motions can be mimicked in real-time by robots.

Ionically Conductive Tunnels in h-WO3 Enable High-Rate NH4 + Storage.

Compared to the commonly applied metallic ion charge carriers (e.g., Li+ and Na+ ), batteries using nonmetallic charge carriers (e.g., H+ and NH4 + ) generally have much faster kinetics and high-rate capability thanks to the small hydrated ionic sizes and nondiffusion control topochemistry. However, the hosts for nonmetallic charge carriers are still limited. In this work, it is suggested that mixed ionic-electronic conductors can serve as a promising host for NH4 + storage. Using hexagonal tungsten oxide (h-WO3 ) as an example, it is shown that the existence of ionic conductive tunnels greatly promotes the high-rate NH4 + storage. Specifically, a much higher capacity of 82 mAh g-1 at 1 A g-1 is achieved on h-WO3 , in sharp contrast to 14 mAh g-1 of monoclinic tungsten oxide (m-WO3 ). In addition, unlike layered materials, the insertion and desertion of NH4 + ions are confined within the tunnels of the h-WO3 , which minimizes the damage to the crystal structure. This leads to outstanding stability of up to 200 000 cycles with 68% capacity retention at a high current of 20 A g-1 .

Muscle Fatigue Sensor Based on Ti3 C2 Tx MXene Hydrogel.

MXene-based hydrogels have received significant attention due to several promising properties that distinguish them from conventional hydrogels. In this study, it is shown that both strain and pH level can be exploited to tune the electronic and ionic transport in MXene-based hydrogel (M-hydrogel), which consists of MXene (Ti3 C2 Tx )-polyacrylic acid/polyvinyl alcohol hydrogel. In particular, the strain applied to the M-hydrogel changes MXene sheet orientation which leads to modulation of ionic transport within the M-hydrogel, due to strain-induced orientation of the surface charge-guided ionic pathway. Simultaneously, the reorientation of MXene sheets under the axial strain increases the electronic resistance of the M-hydrogel due to the loss of the percolative network of conductive MXene sheets during the stretching process. The iontronic characteristics of the M-hydrogel can thus be tuned by strain and pH, which allows using the M-hydrogel as a muscle fatigue sensor during exercise. A fully functional M-hydrogel is developed for real-time measurement of muscle fatigue during exercise and coupled it to a smartphone to provide a portable or wearable digital readout. This concept can be extended to other fields that require accurate analysis of constantly changing physical and chemical conditions, such as physiological changes in the human body.

Ti3C2Tx MXene-Activated Fast Gelation of Stretchable and Self-Healing Hydrogels: A Molecular Approach.

MXene-based hydrogels, a flourishing family of soft materials, have recently emerged as promising candidates for stretchable electronics. Despite recent progress, most works use MXenes as conductive nanofillers. Herein, by tuning the molecular interactions between MXene nanosheets and other constituents within the hydrogels, we demonstrate Ti3C3Tx MXene can act as a versatile cross-linker to activate the fast gelation of a wide range of hydrogels, starting from various monomer- and polymer-based precursors. The gelation behavior varies significantly across hydrogels. In general, the fast gelation mechanism is attributed to the easier generation of free radicals with the help of Ti3C2Tx MXene and the presence of multiscale molecular interactions between MXene and polymers. The use of MXene as a dynamic cross-linker leads to superior mechanical properties, adhesion, and self-healing ability. Owing to the inherent photothermal behavior of Ti3C3Tx and the heterogeneous phase-transforming features of polymers, a polymer-MXene hydrogel is demonstrated to exhibit distinctive thermosensation-based actuation upon near-infrared illumination, accompanied by rapid shape transformation.

MXene Printing and Patterned Coating for Device Applications.

As a thriving member of the 2D nanomaterials family, MXenes, i.e., transition metal carbides, nitrides, and carbonitrides, exhibit outstanding electrochemical, electronic, optical, and mechanical properties. They have been exploited in many applications including energy storage, electronics, optoelectronics, biomedicine, sensors, and catalysis. Compared to other 2D materials, MXenes possess a unique set of properties such as high metallic conductivity, excellent dispersion quality, negative surface charge, and hydrophilicity, making them particularly suitable as inks for printing applications. Printing and pre/post-patterned coating methods represent a whole range of simple, economically efficient, versatile, and eco-friendly manufacturing techniques for devices based on MXenes. Moreover, printing can allow for complex 3D architectures and multifunctionality that are highly required in various applications. By means of printing and patterned coating, the performance and application range of MXenes can be dramatically increased through careful patterning in three dimensions; thus, printing/coating is not only a device fabrication tool but also an enabling tool for new applications as well as for industrialization.

Ultrasound-Driven Two-Dimensional Ti3C2Tx MXene Hydrogel Generator.

Ultrasound is a source of ambient energy that is rarely exploited. In this work, a tissue-mimicking MXene-hydrogel (M-gel) implantable generator has been designed to convert ultrasound power into electric energy. Unlike the present harvesting methods for implantable ultrasound energy harvesters, our M-gel generator is based on an electroacoustic phenomenon known as the streaming vibration potential. Moreover, the output power of the M-gel generator can be improved by coupling with triboelectrification. We demonstrate the potential of this generator for powering implantable devices through quick charging of electric gadgets, buried beneath a centimeter thick piece of beef. The performance is attractive, especially given the extremely simple structure of the generator, consisting of nothing more than encapsulated M-gel. The generator can harvest energy from various ultrasound sources, from ultrasound tips in the lab to the probes used in hospitals and households for imaging and physiotherapy.

Printable Transparent Conductive Films for Flexible Electronics.

Printed electronics are an important enabling technology for the development of low-cost, large-area, and flexible optoelectronic devices. Transparent conductive films (TCFs) made from solution-processable transparent conductive materials, such as metal nanoparticles/nanowires, carbon nanotubes, graphene, and conductive polymers, can simultaneously exhibit high mechanical flexibility, low cost, and better photoelectric properties compared to the commonly used sputtered indium-tin-oxide-based TCFs, and are thus receiving great attention. This Review summarizes recent advances of large-area flexible TCFs enabled by several roll-to-roll-compatible printed techniques including inkjet printing, screen printing, offset printing, and gravure printing using the emerging transparent conductive materials. The preparation of TCFs including ink formulation, substrate treatment, patterning, and postprocessing, and their potential applications in solar cells, organic light-emitting diodes, and touch panels are discussed in detail. The rational combination of a variety of printed techniques with emerging transparent conductive materials is believed to extend the opportunities for the development of printed electronics within the realm of flexible electronics and beyond.