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Messenger RNA (mRNA) cancer vaccines are a new class of immunotherapies that can activate the immune system to recognize and destroy cancer cells. However, their effectiveness in treating colorectal cancer located on the mucosal surface of the gut is limited due to the insufficient activation of mucosal immune response and inadequate infiltration of cytotoxic T cells into tumors. To address this issue, a new mRNA cancer vaccine is developed that can stimulate mucosal immune responses in the gut by co‐delivering all‐trans‐retinoic acid (ATRA) and mRNA using lipid nanoparticle (LNP). The incorporation of ATRA has not only improved the mRNA transfection efficiency of LNP but also induced high expression of gut‐homing receptors on vaccine‐activated T cells. Additionally, the use of LNP improves the aqueous solubility of ATRA, eliminating the need for toxic solvents to administer ATRA. Upon intramuscular injections, ATRA‐adjuvanted mRNA‐LNP significantly increase the infiltration of antigen‐specific, cytotoxic T cells in the lamina propria of the intestine, mesenteric lymph nodes, and orthotopic colorectal tumors, resulting in significantly improved tumor inhibition and prolonged animal survival compared to conventional mRNA‐LNP without ATRA. Overall, this study provides a promising approach for improving the therapeutic efficacy of mRNA cancer vaccines against colorectal cancer. [ABSTRACT FROM AUTHOR]

The receptor‐binding domain (RBD) of spike recognizing the receptor angiotensin‐converting enzyme 2 (ACE2) initiates membrane fusion between severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and cell membrane. Although the structure of the RBD_ACE2 complex has been well studied, its functional mechanism in membrane fusion is still not fully understood. Here, using an in vitro cell–vesicle content‐mixing assay, it is found that the cleavage at the S2' site by thrombin (Thr) protease strongly accelerates membrane fusion, compared to that of cleavage at the S1/S2 site by PreScission (3C) protease. Moreover, mutations at the RBD_ACE2 interface resulted in a positive correlation between binding affinity and fusion probability. In both the cell–vesicle and cell–cell fusion assays, by crosslinking two membranes via the neutravidin (NTV)_biotin interaction or complementary DNA strands, it is found that spike drives membrane fusion in the absence of ACE2, and a suitable distance between two membranes is critical for spike‐mediated membrane fusion. Finally, unsuitable membrane crosslinkers significantly inhibited the fusion probability in the presence of ACE2. Taken together, the results suggest that the RBD_ACE2 complex may act as a crosslinker to bridge the viral and cell membranes at a suitable distance, which is critical, but also substitutable for spike‐mediated SARS‐CoV‐2 entry. [ABSTRACT FROM AUTHOR]

Localized scleroderma (LoS) is a rare chronic disease with extensive tissue fibrosis, inflammatory infiltration, microvascular alterations, and epidermal appendage lesions. However, a deeper understanding of the pathogenesis and treatment strategies of LoS is currently limited. In the present work, a proteome map of LoS skin is established, and the pathological features of LoS skin are characterized. Most importantly, a human‐induced pluripotent stem cell‐derived epithelial and mesenchymal (EM) organoids model in a 3D culture system for LoS therapy is established. According to the findings, the application of EM organoids on scleroderma skin can significantly reduce the degree of skin fibrosis. In particular, EM organoids enhance the activity of epidermal stem cells in the LoS skin and promotes the regeneration of sweat glands and blood vessels. These results highlight the potential application of organoids for promoting the recovery of scleroderma associated phenotypes and skin‐associated functions. Furthermore, it can provide a new therapeutic alternative for patients suffering from disfigurement and skin function defects caused by LoS. [ABSTRACT FROM AUTHOR]

Ferroptosis is a new form of regulated cell death, which is characterized by the iron‐dependent accumulation of lethal lipid peroxides and involved in many critical diseases. Recent reports revealed that cellular energy metabolism activities such as glycolysis, pentose phosphate pathway (PPP), and tricarboxylic acid cycle are involved in the regulation of key ferroptosis markers such as reduced nicotinamide adenine dinucleotide phosphate (NADPH), glutathione (GSH), and reactive oxygen species (ROS), therefore imposing potential regulatory roles in ferroptosis. Remarkably, tumor cells can activate adaptive metabolic responses to inhibit ferroptosis for self‐preservation such as the upregulation of glycolysis and PPP. Due to the rapid proliferation of tumor cells and the intensified metabolic rate, tumor energy metabolism has become a target for disrupting the redox homeostasis and induce ferroptosis. Based on these emerging insights, regulatory impact of those‐tumor specific metabolic aberrations is systematically characterized, such as rewired glucose metabolism and metabolic compensation through glutamine utilization on ferroptosis and analyzed the underlying molecular mechanisms. Additionally, those ferroptosis‐based therapeutic strategies are also discussed by exploiting those metabolic vulnerabilities, which may open up new avenues for tumor treatment in a clinical context. [ABSTRACT FROM AUTHOR]

Rechargeable aqueous zinc ion batteries are enabled by the (de)intercalation chemistry, but bottlenecked by the limited energy density due to the low capacity of cathodes. In this work, carbon nanotubes supported 50 wt% sulfur (denoted as S@CNTs‐50), as a conversional cathode, is employed and a high energy density aqueous zinc–sulfur (Zn–S) battery is constructed. In the electrolyte of 1 m Zn(CH3COO)2 (pH = 6.5) with 0.05 wt% I2 additive where I2 can serve as medium of Zn2+ ions to reduce the voltage hysteresis of S@CNTs‐50 and stabilize Zn stripping/plating, S@CNTs‐50 delivers a high capacity of 1105 mAh g−1 with a flat discharge voltage of 0.5 V, realizing an energy density of 502 Wh kg−1 based on sulfur, which is one of the highest values reported in aqueous Zn‐based batteries that use mild electrolyte. Moreover, the chemical materials cost of this aqueous Zn–S battery can be lowered to be $45 kWh−1 due to the cheap raw materials, reaching to the level of pumped energy storage. Ex situ X‐ray diffraction, Raman spectra, X‐ray photoelectron spectrum, and transmission electron microscopy measurements reveal that sulfur cathode undergoes a conversion reaction between S and ZnS. [ABSTRACT FROM AUTHOR]

Unique metal sulfide (MS) clusters embedded ultrathin nanosheets of Fe/Ni metal–organic framework (MOF) are grown on nickel foam (NiFe‐MS/MOF@NF) as a highly efficient bifunctional electrocatalyst for overall water splitting. It exhibits remarkable catalytic activity and stability toward both the oxygen evolution reaction (OER, ƞ = 230 mV at 50 mA cm−2) and hydrogen evolution reaction (HER, ƞ = 156 mV at 50 mA cm−2) in alkaline media, and bi‐functionally catalyzes overall alkaline water splitting at a current density of 50 mA cm−2 by 1.74 V cell voltage without iR compensation. The enhancement mechanism is ascribed to the impregnated metal sulfide clusters in the nanosheets, which not only promote the formation of ultrathin nanosheet to greatly enlarge the reaction surface area while offering high electric conductivity, but more importantly, efficiently modulate the electronic structure of the catalytically active atom sites to an electron‐rich state via strong electronic interaction and strengthen the adsorption of oxygenate intermediate to facilitate fast electrochemical reactions. This work reports a highly efficient HER/OER bifunctional electrocatalyst and may shed light on the rational design and synthesis of uniquely structured MOF‐derived catalysts. [ABSTRACT FROM AUTHOR]

Substitutional doping of layered transition metal dichalcogenides (TMDs) has been proved to be an effective route to alter their intrinsic properties and achieve tunable bandgap, electrical conductivity and magnetism, thus greatly broadening their applications. However, achieving valid substitutional doping of TMDs remains a great challenge to date. Herein, a distinctive molten‐salt‐assisted chemical vapor deposition (MACVD) method is developed to match the volatilization of the dopants perfectly with the growth process of monolayer MoS2, realizing the substitutional doping of transition metal Fe, Co, and Mn. This doping strategy effectively alters the electronic structure and phononic properties of the pristine MoS2. In addition, a temperature‐dependent Raman spectrum is employed to explore the effect of dopants on the lattice dynamics and first‐order temperature coefficient of monolayer MoS2, and this doping effect is illustrated in depth combined with the theoretical calculation. This work provides an intriguing and powerful doping strategy for TMDs through employing molten salt in the CVD system, paving the way for exploring new properties of 2D TMDs and extending their applications into spintronics, catalytic chemistry and photoelectric devices. [ABSTRACT FROM AUTHOR]

As a very prospective solid‐state electrolyte, Li10GeP2S12 (LGPS) exhibits high ionic conductivity comparable to liquid electrolytes. However, severe self‐decomposition and Li dendrite propagation of LGPS will be triggered due to the thermodynamic incompatibility with Li metal anode. Herein, by adopting a facile chemical vapor deposition method, an artificial solid electrolyte interphase composed of Li2S is proposed as a single ionic conductor to promote the interface stability of LGPS toward Li. The good electronic insulation coupled with ionic conduction property of Li2S effectively blocks electron transfer from Li to LGPS while enabling smooth passage of Li ions. Meanwhile, the generated Li2S layer remains good interface compatibility with LGPS, which is verified by the stable Li‐plating/stripping operation for over 500 h at 0.15 mA cm−2. Consequently, the all‐solid‐state Li–S batteries (ASSLSBs) with a Li2S layer demonstrate superb capacity retention of 90.8% at 0.2 mA cm−2 after 100 cycles. Even at the harsh condition of 90 °C, the cell can deliver a high reversible capacity of 1318.8 mAh g−1 with decent capacity retention of 88.6% after 100 cycles. This approach offers a new insight for interface modification between LGPS and Li and the realization of ASSLSBs with stable cycle life. [ABSTRACT FROM AUTHOR]

CRISPR‐based gene therapies are making remarkable strides toward the clinic. But the large size of most widely used Cas endonucleases including Cas9 and Cas12a restricts their efficient delivery by the adeno‐associated virus (AAV) for in vivo gene editing. Being exceptionally small, the recently engineered type V‐F CRISPR‐Cas12f1 systems can overcome the cargo packaging bottleneck and present as strong candidates for therapeutic applications. In this study, the pairwise editing efficiencies of different engineered Cas12f1/sgRNA scaffold combinations are systemically screened and optimized, and the CasMINI_v3.1/ge4.1 system is identified as being able to significantly boost the gene editing activity. Moreover, packaged into single AAV vectors and delivered via subretinal injection, CasMINI_v3.1/ge4.1 achieves remarkably high in vivo editing efficiencies, over 70% in transduced retinal cells. Further, the efficacy of this Cas12f1 system‐based gene therapy to treat retinitis pigmentosa in RhoP23H mice is demonstrated by the therapeutic benefits achieved including rescued visual function and structural preservation. And minimal bystander editing activity is detected. This work advances and expands the therapeutic potential of the miniature Cas12f1 system to support efficient and accurate in vivo gene therapy. [ABSTRACT FROM AUTHOR]

Secondary trastuzumab resistance represents an evolutionary adaptation of HER2‐positive breast cancer during anti‐HER2 treatment. Most current studies have tended to prioritize HER2 and its associated signaling pathways, often overlooking broader but seemingly less relevant cellular processes, along with their associated genetic and epigenetic mechanisms. Here, transcriptome data is not only characterized but also examined epigenomic and 3D genome architecture information in both trastuzumab‐sensitive and secondary‐resistant breast cancer cells. The findings reveal that the global metabolic reprogramming associated with trastuzumab resistance may stem from genome‐wide alterations in both histone modifications and chromatin structure. Specifically, the transcriptional activities of key genes involved in lipid metabolism appear to be regulated by variant promoter H3K27me3 and H3K4me3 modifications, as well as promoter‐enhancer interactions. These discoveries offer valuable insights into how cancer cells adapt to anti‐tumor drugs and have the potential to impact future diagnostic and treatment strategies. [ABSTRACT FROM AUTHOR]

Most multiplex nucleic acids detection methods require numerous reagents and high‐priced instruments. The emerging clustered regularly interspaced short palindromic repeats (CRISPR)/Cas has been regarded as a promising point‐of‐care (POC) strategy for nucleic acids detection. However, how to achieve CRISPR/Cas multiplex biosensing remains a challenge. Here, an affordable means termed CRISPR‐RDB (CRISPR‐based reverse dot blot) for multiplex target detection in parallel, which possesses the advantages of high sensitivity and specificity, cost‐effectiveness, instrument‐free, ease to use, and visualization is reported. CRISPR‐RDB integrates the trans‐cleavage activity of CRISPR‐Cas12a with a commercial RDB technique. It utilizes different Cas12a‐crRNA complexes to separately identify multiple targets in one sample and converts targeted information into colorimetric signals on a piece of accessible nylon membrane that attaches corresponding specific‐oligonucleotide probes. It has demonstrated that the versatility of CRISPR‐RDB by constructing a four‐channel system to simultaneously detect influenza A, influenza B, respiratory syncytial virus, and SARS‐CoV‐2. With a simple modification of crRNAs, the CRISPR‐RDB can be modified to detect human papillomavirus, saving two‐thirds of the time compared to a commercial PCR‐RDB kit. Further, a user‐friendly microchip system for convenient use, as well as a smartphone app for signal interpretation, is engineered. CRISPR‐RDB represents a desirable option for multiplexed biosensing and on‐site diagnosis. [ABSTRACT FROM AUTHOR]

B Localized Scleroderma Therapy b Human-induced pluripotent stem cell (hiPSC)-derived epithelial and mesenchymal (EM) organoids can be used to investigate the therapeutic potential for the recovery of localized scleroderma (LoS) associated phenotypes and skin-associated functions. In article number 2106075, Wu Zhong, Shuyang Zhang, Ling Leng, and co-workers, establish an experimental EM organoid model from hiPSC to significantly reduce the degree of skin fibrosis and inflammation. Most importantly, it promotes the regeneration of epidermis and their appendages, providing a new therapeutic alternative for patients suffering from disfigurement and skin function defects caused by LoS. [Extracted from the article]

Previously a ring finger protein 20 (RNF20) is found to be essential for meiotic recombination and mediates H2B ubiquitination during spermatogenesis. However, its role in meiotic division is still unknown. Here, it is shown that RNF20 is localized at both centromeres and spindle poles, and it is required for oocyte acentrosomal spindle organization and female fertility. RNF20‐depleted oocytes exhibit severely abnormal spindle and chromosome misalignment caused by defective bipolar organization. Notably, it is found that the function of RNF20 in spindle assembly is not dependent on its E3 ligase activity. Instead, RNF20 regulates spindle assembly by recruiting tropomyosin3 (TPM3) to both centromeres and spindle poles with its coiled‐coil motif. The RNF20‐TPM3 interaction is essential for acentrosomal meiotic spindle assembly. Together, the studies uncover a novel function for RNF20 in mediating TPM3 recruitment to both centromeres and spindle poles during oocyte spindle assembly. [ABSTRACT FROM AUTHOR]

Exploration of medicines for efficient and safe management of metabolic‐associated fatty liver disease (MAFLD) remains a challenge. Obeticholic acid (OCA), a selective farnesoid X receptor agonist, has been reported to ameliorate injury and inflammation in various liver diseases. However, its clinical application is mainly limited by poor solubility, low bioavailability, and potential side effects. Herein a hepatic‐targeted nanodrugs composed of OCA and cholesterol‐lowering atorvastatin (AHT) with an ideal active pharmaceutical ingredient (API) content for orally combined treatment of MAFLD is created. Such carrier‐free nanocrystals (OCAHTs) are self‐assembled, not only improving the stability in gastroenteric environments but also achieving hepatic accumulation through the bile acid transporter‐mediated enterohepatic recycling process. Orally administrated OCAHT outperforms the simple combination of OCA and AHT in ameliorating of liver damage and inflammation in both acetaminophen‐challenged mice and high‐fat diet‐induced MAFLD mice with less systematic toxicity. Importantly, OCAHT exerts profoundly reverse effects on MAFLD‐associated molecular pathways, including impairing lipid metabolism, reducing inflammation, and enhancing the antioxidation response. This work not only provides a facile bile acid transporter‐based strategy for hepatic‐targeting drug delivery but also presents an efficient and safe full‐API nanocrystal with which to facilitate the practical translation of nanomedicines against MAFLD. [ABSTRACT FROM AUTHOR]

Proton exchange membrane fuel cells (PEMFCs) have garnered significant attention due to their high efficiency and low emissions. However, PEMFC always suffers mass transfer and water management in performance improvement. Herein, an integrated gas diffusion layer (GDL) with wavy channel and micro‐tunneled rib is designed and prepared to achieve faster and gentler mass transfer and excellent water management capability by laser engraving. Outstandingly, the new integrated GDL can use the back pressure of air as low as 0 and 50 kPa to respectively achieve 80% and 90% of fuel cell performance realized under pure oxygen. Such high performance is mainly due to the turbulent flow caused by wavy channel and express removing pathway of liquid water provided by micro‐tunneled rib. Moreover, the new integrated GDL also shows wide humidity tolerance from 40% to 100% and a very high specific volume power density of 16,300 W L−1 due to the thin thickness of new integrated GDL. This new integrated GDL is expected to be widely used in PEMFC and other energy conversion devices. [ABSTRACT FROM AUTHOR]

Sulfur is considered to be one of the most promising cathode materials due to its high theoretical specific capacity and low cost. However, the insulating nature of sulfur and notorious "shuttle effect" of lithium polysulfides (LiPSs) lead to severe loss of active sulfur, poor redox kinetics, and rapid capacity fade. Herein, a hierarchical electrode design is proposed to address these issues synchronously, which integrates multiple building blocks with specialized functions into an ensemble to construct a self‐supported versatile cathode for lithium–sulfur batteries. Nickel foam acts as a robust conductive scaffold. The heteroatom‐doped host carbon with desired lithiophilicity and electronic conductivity serving as a reservoir for loading sulfur can trap LiPSs and promote electron transfer to interfacial adsorbed LiPSs and Ni3S2 sites. The sulfurized carbon nanofiber forest can facilitate the Li‐ion and electron transport and retard the LiPSs diffusion as a barrier layer. Sulfiphilic Ni3S2 acts as both a chemical anchor with strong adsorption affinity to LiPSs and an efficient electrocatalyst for accelerating kinetics for redox conversion reactions. Synergistically, all functional units promote the lithium ion coupled electron transfer for binding and redox conversion of LiPSs, resulting in high reversible capacities, remarkable cycle stability, and excellent rate capability. [ABSTRACT FROM AUTHOR]

T‐cell acute lymphoblastic leukemia (T‐ALL) is an aggressive malignant blood disorder with a high rate of relapse. Patients relapse as a result of minimal residual disease (MRD), which originates from residual T‐ALL cells in the bone marrow microenvironment (BMM). In the present study, it is observed that adipocytes increase dramatically in the BMM of T‐ALL patients after exposure to chemotherapeutic drugs. Then, it is proved that adipocytes attract T‐ALL cells by releasing CXCL13 and support leukemia cell survival by activating the Notch1 signaling pathway via DLL1 and Notch1 binding. Furthermore, it is verified that dexamethasone (DEX) induces adipogenic differentiation by enhancing the expression of SREBF1 in bone marrow mesenchymal stromal cells (BMSCs), and an SREBF1 inhibitor significantly decreases the adipogenic potential of BMSCs and the subsequent ability of adipocytes to support T‐ALL cells in vitro and in vivo. These findings confirm that the differentiation of BMSCs to adipocytes induced by DEX contributes to MRD in T‐ALL and provides an auxiliary clinical treatment to reduce the recurrence rate. [ABSTRACT FROM AUTHOR]

Triple‐negative breast cancer (TNBC) has higher molecular heterogeneity and metastatic potential and the poorest prognosis. Because of limited therapeutics against TNBC, irradiation (IR) therapy is still a common treatment option for patients with lymph nodes or brain metastasis. Thus, it is urgent to develop strategies to enhance the sensitivity of TNBC tumors to low‐dose IR. Here, the authors report that E3 ubiquitin ligase Ring finger protein 126 (RNF126) is important for IR‐induced ATR‐CHK1 pathway activation to enhance DNA damage repair (DDR). Mechanistically, RNF126 physically associates with the MRE11‐RAD50‐NBS1 (MRN) complex and ubiquitinates MRE11 at K339 and K480 to increase its DNA exonuclease activity, subsequent RPA binding, and ATR phosphorylation, promoting sustained DDR in a homologous recombination repair‐prone manner. Accordingly, depletion of RNF126 leads to increased genomic instability and radiation sensitivity in both TNBC cells and mice. Furthermore, it is found that RNF126 expression is induced by IR activating the HER2‐AKT‐NF‐κB pathway and targeting RNF126 expression with dihydroartemisinin significantly improves the sensitivity of TNBC tumors in the brain to IR treatment in vivo. Together, these results reveal that RNF126‐mediated MRE11 ubiquitination is a critical regulator of the DDR, which provides a promising target for improving the sensitivity of TNBC to radiotherapy. [ABSTRACT FROM AUTHOR]

T‐cell acute lymphoblastic leukemia (T‐ALL) is an aggressive hematological malignancy with a poor prognosis, urging for novel therapeutic targets and treatment strategies. N6‐methyladenosine (m6A) is a crucial methylation modification that affects the pathogenesis of leukemia by regulating the mRNA of key genes. Interferon regulatory factor 8 (IRF8) is a crucial transcription factor for hematological lineage commitment, but its role in T‐ALL is unclear. Here, IRF8 is shown to suppress T‐ALL. The expression of IRF8 is abnormally silenced in patients with T‐ALL. Knockout of Irf8 significantly hastens the progression of Notch1‐induced T‐ALL in vivo. Overexpression of IRF8 suppresses the proliferation and invasion of T‐ALL cells by inhibiting the phosphatidylinositol 3‐kinase/AKT signaling pathway. The fat mass‐ and obesity‐associated protein (FTO), an m6A demethylase, is responsible for directly binding to m6A sites in 3′ untranslated region of IRF8 messenger RNA (mRNA) and inducing mRNA degradation via m6A modification. Targeting the FTO‐IRF8 axis is used as a proof of concept therapy; inhibition of FTO's demethylase activity drastically alleviates the proliferation of leukemic cells and prolongs the survival of T‐ALL mice by restoring IRF8 expression. This study elucidates the pathogenesis of T‐ALL from the perspective of epitranscriptomics and provides new insight into the genetic mechanisms and targeted therapy of T‐ALL. [ABSTRACT FROM AUTHOR]

CRISPR Gene TherapyIn article number 2308095, Wei Li, Fei Teng, and colleagues introduce a hypercompact CRISPR‐Cas12f1 system characterized by enhanced gene editing capabilities and minimal off‐target effects. Applied to the treatment of inherited retinal diseases, this system shows significant therapeutic outcomes, highlighting its substantial promise for gene therapy applications..By Tongtong Cui; Bingyu Cai; Yao Tian; Xin Liu; Chen Liang; Qingqin Gao; Bojin Li; Yali Ding; Rongqi Li; Qi Zhou; Wei Li and Fei TengReported by Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author [Extracted from the article]

Fundamental understanding and control of the electronic structure evolution in rare‐earth nickelates is a fascinating and meaningful issue, as well as being helpful to understand the mechanism of recently discovered superconductivity. Here the dimensionality effect on the ground electronic state in high‐quality (NdNiO3) m/(SrTiO3)1 superlattices is systematically studied through transport and soft X‐ray absorption spectroscopy. The metal‐to‐insulator transition temperature decreases with the thickness of the NdNiO3 slab decreasing from bulk to 7 unit cells, then increases gradually as m further reduces to 1 unit cell. Spectral evidence demonstrates that the stabilization of insulating phase can be attributed to the increase of the charge‐transfer energy between O 2p and Ni 3d bands. The prominent multiplet feature on the Ni L3 edge develops with the decrease of NdNiO3 slab thickness, suggesting the strengthening of the charge disproportionate state under the dimensional confinement. This work provides convincing evidence that dimensionality is an effective knob to modulate the charge‐transfer energy and thus the collective ground state in nickelates. [ABSTRACT FROM AUTHOR]

Flexibly and precisely manipulating 3D droplet transportation is a fundamental challenge for broad implications in diagnostics, drug delivery, bioengineering, etc. Herein, a light method is developed for manipulating a droplet to make it behave like a submarine. This light method enables flexible 3D transportation, stable suspension, and floating of a droplet, which can be freely altered. It is demonstrated that the localized photothermal effect induced thermocapillary flow in the water droplet/oil phase is responsible for energizing and manipulating the droplet. With such remarkable motility, the light‐fueled submarine‐like droplet successfully realizes various functions such as the acid‐base detection, particle capture and transportation, and target crystal collection, dissolution and transportation. It is demonstrated that the light‐fueled submarine‐like droplet shows promising perspective for long‐sought precise droplet manipulation in various applications. [ABSTRACT FROM AUTHOR]

Carbonaceous materials are considered strong candidates as anode materials for sodium‐ion batteries (SIBs), which are expected to play an indispensable role in the carbon‐neutral era. Herein, novel braided porous carbon fibres (BPCFs) are prepared using the chemical vapour deposition (CVD) method. The BPCFs possess interwoven porous structures and abundant vacancies. The growth mechanism of the BPCFs can be attributed to the polycrystalline transformation of the nanoporous copper catalyst in the early stage of CVD process. Density functional theory calculations suggest that the Na+ adsorption energies of the mono‐vacancy edges of the BPCFs (−1.22 and −1.09 eV) are lower than that of an ideal graphene layer (−0.68 eV), clarifying in detail the adsorption‐dominated sodium storage mechanism. Hence, the BPCFs as an anode material present an outstanding discharge capacity of 401 mAh g−1 at 0.1 A g−1 after 500 cycles. Remarkably, this BPCFs anode, under high‐mass‐loading of 5 mg cm−2, shows excellent long‐term cycling ability with a reversible capacity of 201 mAh g−1 at 10 A g−1 over 1000 cycles. This study provided a novel strategy for the development of high‐performance carbonaceous materials for SIBs. [ABSTRACT FROM AUTHOR]

Direct cell reprogramming, also called transdifferentiation, is valuable for cell fate studies and regenerative medicine. Current approaches to transdifferentiation are usually achieved by directly targeting the nuclear functions, such as manipulating the lineage‐specific transcriptional factors, microRNAs, and epigenetic modifications. Here, a robust method to convert fibroblasts to neurons through targeting the cytoskeleton followed by exposure to lineage‐specification surroundings is reported. Treatment of human foreskin fibroblasts with a single molecule inhibitor of the actomyosin contraction, can disrupt the cytoskeleton, promote cell softening and nuclear export of YAP/TAZ, and induce a neuron‐like state. These neuron‐like cells can be further converted into mature neurons, while single‐cell RNA‐seq shows the homogeneity of these cells during the induction process. Finally, transcriptomic analysis shows that cytoskeletal disruption collapses the original lineage expression profile and evokes an intermediate state. These findings shed a light on the underestimated role of the cytoskeleton in maintaining cell identity and provide a paradigm for lineage conversion through the regulation of mechanical properties. [ABSTRACT FROM AUTHOR]

The Hippo pathway effector TAZ promotes cellular growth, survival, and stemness through regulating gene transcription. Recent studies suggest that TAZ liquid–liquid phase separation (LLPS) compartmentalizes key cofactors to activate transcription. However, how TAZ LLPS is achieved remains unknown. Here, it is shown that the paraspeckle protein NONO is required for TAZ LLPS and activation in the nucleus. NONO is a TAZ‐binding protein. Their interaction shows temporal regulation parallel to the interaction between TAZ and TEAD as well as to the expression of TAZ target genes. NONO depletion reduces nuclear TAZ LLPS, while ectopic NONO expression promotes the LLPS. Accordingly, NONO depletion reduces TAZ interactions with TEAD, Rpb1, and enhancers. In glioblastoma, expressions of NONO and TAZ are both upregulated and predict poor prognosis. Silencing NONO expression in an orthotopic glioblastoma mouse model inhibits TAZ‐driven tumorigenesis. Together, this study suggests that NONO is a nuclear factor that promotes TAZ LLPS and TAZ‐driven oncogenic transcriptional program. [ABSTRACT FROM AUTHOR]

Necrosis induces strong inflammation with undesirable implications in clinics compared with apoptosis. Fortunately, the switch between necrosis and apoptosis could be realized by tailoring the appropriate structural properties of gold nano rods (GNRs) that could precisely modulate cell death pathways. Herein, the intracellular interaction between GNRs and organelles is monitored and it is found that lysosomes dominates necrosis/apoptosis evoking. Then the surface molecule density of GNRs, which is first defined as ρsurf. molecule (Nsurf. molecules/(a × π × Diameter × Length)), mediates lysosome activities as the membrane permeabilization (LMP), the Cathepsin B and D release, the cross‐talk between lysosome and different organelles, which selectively evokes apoptosis or necrosis and the production of TNF‐α from macrophages. GNRs with small ρsurf. molecule mainly induce apoptosis, while with large ρsurf. molecule they greatly contribute to necrosis. Interestingly, necrosis can be suppressed by GNRs with higher ρsurf. molecule due to the overexpression of key protease caspase 8, which cleaves the RIP1‐RIP3 complex and activates caspase 3 followed by necrosis to apoptosis transition. This investigation indicates that the ρsurf. molecule greatly affects the utility of nanomaterials and different structural properties of nanomaterials have different implications in clinics. [ABSTRACT FROM AUTHOR]

Organic/inorganic hybrid fibers (OIHFs) are intriguing materials, possessing an intrinsic high specific surface area and flexibility coupled to unique anisotropic properties, diverse chemical compositions, and controllable hybrid architectures. During the last decade, advanced OIHFs with exceptional properties for electrochemical energy applications, including possessing interconnected networks, abundant active sites, and short ion diffusion length have emerged. Here, a comprehensive overview of the controllable architectures and electrochemical energy applications of OIHFs is presented. After a brief introduction, the controllable construction of OIHFs is described in detail through precise tailoring of the overall, interior, and interface structures. Additionally, several important electrochemical energy applications including rechargeable batteries (lithium‐ion batteries, sodium‐ion batteries, and lithium–sulfur batteries), supercapacitors (sandwich‐shaped supercapacitors and fiber‐shaped supercapacitors), and electrocatalysts (oxygen reduction reaction, oxygen evolution reaction, and hydrogen evolution reaction) are presented. The current state of the field and challenges are discussed, and a vision of the future directions to exploit OIHFs for electrochemical energy devices is provided. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) metastasizes mainly to the liver, which accounts for the majority of CRC‐related deaths. Here it is shown that metastatic cells undergo specific chromatin remodeling in the liver. Hepatic growth factor (HGF) induces phosphorylation of PU.1, a pioneer factor, which in turn binds and opens chromatin regions of downstream effector genes. PU.1 increases histone acetylation at the DPP4 locus. Precise epigenetic silencing by CRISPR/dCas9KRAB or CRISPR/dCas9HDAC revealed that individual PU.1‐remodeled regulatory elements collectively modulate DPP4 expression and liver metastasis growth. Genetic silencing or pharmacological inhibition of each factor along this chromatin remodeling axis strongly suppressed liver metastasis. Therefore, microenvironment‐induced epimutation is an important mechanism for metastatic tumor cells to grow in their new niche. This study presents a potential strategy to target chromatin remodeling in metastatic cancer and the promise of repurposing drugs to treat metastasis. [ABSTRACT FROM AUTHOR]

The low delivery efficiency of nanoparticles to solid tumors greatly reduces the therapeutic efficacy and safety which is closely related to low permeability and poor distribution at tumor sites. In this work, an "intrinsic plus extrinsic superiority" administration strategy is proposed to dramatically enhance the mean delivery efficiency of nanoparticles in prostate cancer to 6.84% of injected dose, compared to 1.42% as the maximum in prostate cancer in the previously reported study. Specifically, the intrinsic superiority refers to the virus‐mimic surface topology of the nanoparticles for enhanced nano–bio interactions. Meanwhile, the extrinsic stimuli of microbubble‐assisted low‐frequency ultrasound is to enhance permeability of biological barriers and improve intratumor distribution. The enhanced intratumor enrichment can be verified by photoacoustic resonance imaging, fluorescence imaging, and magnetic resonance imaging in this multifunctional nanoplatform, which also facilitates excellent anticancer effect of photothermal treatment, photodynamic treatment, and sonodynamic treatment via combined laser and ultrasound irradiation. This study confirms the significant advance in nanoparticle accumulation in multiple tumor models, which provides an innovative delivery paradigm to improve intratumor accumulation of nanotherapeutics. [ABSTRACT FROM AUTHOR]

The low delivery efficiency of nanoparticles to solid tumors greatly reduces the therapeutic efficacy and safety which is closely related to low permeability and poor distribution at tumor sites. In this work, an "intrinsic plus extrinsic superiority" administration strategy is proposed to dramatically enhance the mean delivery efficiency of nanoparticles in prostate cancer to 6.84% of injected dose, compared to 1.42% as the maximum in prostate cancer in the previously reported study. Specifically, the intrinsic superiority refers to the virus‐mimic surface topology of the nanoparticles for enhanced nano–bio interactions. Meanwhile, the extrinsic stimuli of microbubble‐assisted low‐frequency ultrasound is to enhance permeability of biological barriers and improve intratumor distribution. The enhanced intratumor enrichment can be verified by photoacoustic resonance imaging, fluorescence imaging, and magnetic resonance imaging in this multifunctional nanoplatform, which also facilitates excellent anticancer effect of photothermal treatment, photodynamic treatment, and sonodynamic treatment via combined laser and ultrasound irradiation. This study confirms the significant advance in nanoparticle accumulation in multiple tumor models, which provides an innovative delivery paradigm to improve intratumor accumulation of nanotherapeutics. [ABSTRACT FROM AUTHOR]

Corneal neovascularization (CNV) is one of the main factors that induce blindness worldwide. However, current medical treatments cannot achieve non‐invasive and safe inhibition of CNV. A noninvasive photoacoustic imaging (PAI)‐guided method is purposed for the regression of CNV. PAI can monitor the oxygen saturation of cornea blood vessels through the endogenous contrast of hemoglobin and trace administrated drugs by themselves as exogenous contrast agents. An indocyanine green (ICG)‐based nanocomposite (R‐s‐ICG) is prepared for CNV treatment via eye drops and subconjunctival injections. It is demonstrated that R‐s‐ICG can enrich corneal tissues and pathological blood vessels rapidly with minor residua in normal eyeball tissues. Anti‐CNV treatment‐driven changes in the blood vessels are assessed by real‐time multimodal PAI in vivo, and then a safe laser irradiation strategy through the canthus is developed for phototherapy and gene therapy synergistic treatment. The treatment leads to the efficient inhibition of CNV with faint damages to normal tissues. [ABSTRACT FROM AUTHOR]

Lean electrolyte (small E/S ratio) is urgently needed to achieve high practical energy densities in Li–S batteries, but there is a distinction between the cathode's absorbed electrolyte (AE) which is cathode‐intrinsic and total added electrolyte (E) which depends on cell geometry. While total pore volume in sulfur cathodes affects AE/S and performance, it is shown here that pore morphology, size, connectivity, and fill factor all matter. Compared to conventional thermally dried sulfur cathodes that usually render "open lakes" and closed pores, a freeze‐dried and compressed (FDS‐C) sulfur cathode is developed with a canal‐capillary pore structure, which exhibits high mean performance and greatly reduces cell‐to‐cell variation, even at high sulfur loading (14.2 mg cm−2) and ultralean electrolyte condition (AE/S = 1.2 µL mg−1). Interestingly, as AE/S is swept from 2 to 1.2 µL mg−1, the electrode pores go from fully flooded to semi‐flooded, and the coin cell still maintains function until (AE/S)min ≈ 1.2 µL mg−1 is reached. When scaled up to Ah‐level pouch cells, the full‐cell energy density can reach 481 Wh kg−1 as its E/S ≈ AE/S ratio can be reduced to 1.2 µL mg−1, proving high‐performance pouch cells can actually be working in the ultralean, semi‐flooded regime. [ABSTRACT FROM AUTHOR]

Meiosis increases genetic diversity, yet the genome complement needs to be stable to ensure offspring viability. Both small ubiquitin‐like modifier (SUMO) and ubiquitin have been reported to participate in meiotic regulation, yet functions of the SUMO‐ubiquitination crosstalk in meiosis remain unclear. Here, it is reported that a SUMO‐targeted ubiquitin ligase, Slx8p, promotes accurate chromosome segregation during meiosis, since the deletion of SLX8 leads to increased aneuploidy due to a defect in synaptonemal complex (SC) component degradation. Both the RING domain and SUMO interacting motifs of Slx8p are essential for meiotic progression and maintaining spore viability, and the expression of tetraubiquitin fused with SUMO partially rescues meiotic defects in the SLX8‐deletion strain. Furthermore, Slx5p‐Slx8p can directly add ubiquitin to SUMOylated Zip1p and Ecm11p, and forced degradation of Ecm11p partially rescues the sporulation defects of the SLX8 deletion strain. These findings provide a mechanism for SC disassembly and reveal that the crosstalk between SUMOylation and ubiquitination facilitates accurate chromosome segregation by promoting SC component degradation during meiosis. [ABSTRACT FROM AUTHOR]

DEX-Induced SREBF1 Promotes BMSCs Differentiation into Adipocytes to Attract and Protect Residual T-Cell Acute Lymphoblastic Leukemia Cells After Chemotherapy (Adv. Sci. 19/2023) Last, an SREBF1 inhibitor demonstrates superior improvement on therapeutic effect of dexamethason by reducing adipogenesis and provides a feasible strategy to solve the dilemma of recurrence. B T-Cell Acute Lym-phoblastic Leukemia b In article number 2205854, Jingjing Ye, Min Ji, Chunyan Ji, and co-workers observed aberrant adipogenesis in the bone marrow of chemotherapy-treated T-cell acute lymphoblastic leukemia (T-ALL) patients, and the differentiated-adipocytes attract and support residual T-ALL cells. [Extracted from the article]