Adaptive evolution of the enigmatic Takakia now facing climate change in Tibet.

The most extreme environments are the most vulnerable to transformation under a rapidly changing climate. These ecosystems harbor some of the most specialized species, which will likely suffer the highest extinction rates. We document the steepest temperature increase (2010-2021) on record at altitudes of above 4,000 m, triggering a decline of the relictual and highly adapted moss Takakia lepidozioides. Its de-novo-sequenced genome with 27,467 protein-coding genes includes distinct adaptations to abiotic stresses and comprises the largest number of fast-evolving genes under positive selection. The uplift of the study site in the last 65 million years has resulted in life-threatening UV-B radiation and drastically reduced temperatures, and we detected several of the molecular adaptations of Takakia to these environmental changes. Surprisingly, specific morphological features likely occurred earlier than 165 mya in much warmer environments. Following nearly 400 million years of evolution and resilience, this species is now facing extinction.

Multiphase coalescence mediates Hippo pathway activation.

The function of biomolecular condensates is often restricted by condensate dissolution. Whether condensates can be suppressed without condensate dissolution is unclear. Here, we show that upstream regulators of the Hippo signaling pathway form functionally antagonizing condensates, and their coalescence into a common phase provides a mode of counteracting the function of biomolecular condensates without condensate dissolution. Specifically, the negative regulator SLMAP forms Hippo-inactivating condensates to facilitate pathway inhibition by the STRIPAK complex. In response to cell-cell contact or osmotic stress, the positive regulators AMOT and KIBRA form Hippo-activating condensates to facilitate pathway activation. The functionally antagonizing SLMAP and AMOT/KIBRA condensates further coalesce into a common phase to inhibit STRIPAK function. These findings provide a paradigm for restricting the activity of biomolecular condensates without condensate dissolution, shed light on the molecular principles of multiphase organization, and offer a conceptual framework for understanding upstream regulation of the Hippo signaling pathway.

Chemistry-First Approach for Nomination of Personalized Treatment in Lung Cancer.

Diversity in the genetic lesions that cause cancer is extreme. In consequence, a pressing challenge is the development of drugs that target patient-specific disease mechanisms. To address this challenge, we employed a chemistry-first discovery paradigm for de novo identification of druggable targets linked to robust patient selection hypotheses. In particular, a 200,000 compound diversity-oriented chemical library was profiled across a heavily annotated test-bed of >100 cellular models representative of the diverse and characteristic somatic lesions for lung cancer. This approach led to the delineation of 171 chemical-genetic associations, shedding light on the targetability of mechanistic vulnerabilities corresponding to a range of oncogenotypes present in patient populations lacking effective therapy. Chemically addressable addictions to ciliogenesis in TTC21B mutants and GLUT8-dependent serine biosynthesis in KRAS/KEAP1 double mutants are prominent examples. These observations indicate a wealth of actionable opportunities within the complex molecular etiology of cancer.

Reconstructed covalent organic frameworks.

Covalent organic frameworks (COFs) are distinguished from other organic polymers by their crystallinity1-3, but it remains challenging to obtain robust, highly crystalline COFs because the framework-forming reactions are poorly reversible4,5. More reversible chemistry can improve crystallinity6-9, but this typically yields COFs with poor physicochemical stability and limited application scope5. Here we report a general and scalable protocol to prepare robust, highly crystalline imine COFs, based on an unexpected framework reconstruction. In contrast to standard approaches in which monomers are initially randomly aligned, our method involves the pre-organization of monomers using a reversible and removable covalent tether, followed by confined polymerization. This reconstruction route produces reconstructed COFs with greatly enhanced crystallinity and much higher porosity by means of a simple vacuum-free synthetic procedure. The increased crystallinity in the reconstructed COFs improves charge carrier transport, leading to sacrificial photocatalytic hydrogen evolution rates of up to 27.98 mmol h-1 g-1. This nanoconfinement-assisted reconstruction strategy is a step towards programming function in organic materials through atomistic structural control.

Genome-wide chromatin interaction profiling reveals a vital role of super-enhancers and rearrangements in host enhancer contacts during BmNPV infection.

As influential regulatory elements in the genome, enhancers control gene expression under specific cellular conditions, and such connections are dynamic under different conditions. However, because of the lack of a genome-wide enhancer-gene connection map, the roles and regulatory pattern of enhancers were poorly investigated in insects, and the dynamic changes of enhancer contacts and functions under different conditions remain elusive. Here, combining Hi-C, ATAC-seq, and H3K27ac ChIP-seq data, we generate the genome-wide enhancer-gene map of silkworm and identify super-enhancers with a role in regulating the expression of vital genes related to cell state maintenance through a sophisticated interaction network. Additionally, a radical attenuation of chromatin interactions is found after infection of Bombyx mori nucleopolyhedrovirus (BmNPV), the main pathogen of silkworm, which directly rearranges the enhancer contacts. Such a rearrangement disturbs the intrinsic enhancer-gene connections in several antiviral genes, resulting in reduced expression of these genes, which accelerates viral infection. Overall, our results reveal the regulatory role of super-enhancers and shed new light on the mechanisms and dynamic changes of the genome-wide enhancer regulatory network.

The development of catalysts and auxiliaries for the synthesis of covalent organic frameworks.

Covalent organic frameworks (COFs) have recently seen significant advancements. Large quantities of structurally & functionally oriented COFs with a wide range of applications, such as gas adsorption, catalysis, separation, and drug delivery, have been explored. Recent achievements in this field are primarily focused on advancing synthetic methodologies, with catalysts playing a crucial role in achieving highly crystalline COF materials, particularly those featuring novel linkages and chemistry. A series of reviews have already been published over the last decade, covering the fundamentals, synthesis, and applications of COFs. However, despite the pivotal role that catalysts and auxiliaries play in forming COF materials and adjusting their properties (e.g., crystallinity, porosity, stability, and morphology), limited attention has been devoted to these essential components. In this Critical Review, we mainly focus on the state-of-the-art progress of catalysts and auxiliaries applied to the synthesis of COFs. The catalysts include four categories: acid catalysts, base catalysts, transition-metal catalysts, and other catalysts. The auxiliaries, such as modulators, oxygen, and surfactants, are discussed as well. This is then followed by the description of several specific applications derived from the utilization of catalysts and auxiliaries. Lastly, a perspective on the major challenges and opportunities associated with catalysts and auxiliaries is provided.

Spatially and Temporally Resolved Dynamic Response of Co-Based Composite Interface during the Oxygen Evolution Reaction.

Interfacial interaction dictates the overall catalytic performance and catalytic behavior rules of the composite catalyst. However, understanding of interfacial active sites at the microscopic scale is still limited. Importantly, identifying the dynamic action mechanism of the "real" active site at the interface necessitates nanoscale, high spatial-time-resolved complementary-operando techniques. In this work, a Co3O4 homojunction with a well-defined interface effect is developed as a model system to explore the spatial-correlation dynamic response of the interface toward oxygen evolution reaction. Quasi in situ scanning transmission electron microscopy-electron energy-loss spectroscopy with high spatial resolution visually confirms the size characteristics of the interface effect in the spatial dimension, showing that the activation of active sites originates from strong interfacial electron interactions at a scale of 3 nm. Multiple time-resolved operando spectroscopy techniques explicitly capture dynamic changes in the adsorption behavior for key reaction intermediates. Combined with density functional theory calculations, we reveal that the dynamic adjustment of multiple adsorption configurations of intermediates by highly activated active sites at the interface facilitates the O-O coupling and *OOH deprotonation processes. The dual dynamic regulation mechanism accelerates the kinetics of oxygen evolution and serves as a pivotal factor in promoting the oxygen evolution activity of the composite structure. The resulting composite catalyst (Co-B@Co3O4/Co3O4 NSs) exhibits an approximately 70-fold turnover frequency and 20-fold mass activity than the monomer structure (Co3O4 NSs) and leads to significant activity (η10 ∼257 mV). The visual complementary analysis of multimodal operando/in situ techniques provides us with a powerful platform to advance our fundamental understanding of interfacial structure-activity relationships in composite structured catalysts.

Defect-Rich Metastable MoS2 Promotes Macrophage Reprogramming in Breast Cancer: A Clinical Perspective.

Tumor-associated macrophages (TAMs) play a crucial function in solid tumor antigen clearance and immune suppression. Notably, 2D transitional metal dichalcogenides (i.e., molybdenum disulfide (MoS2) nanozymes) with enzyme-like activity are demonstrated in animal models for cancer immunotherapy. However, in situ engineering of TAMs polarization through sufficient accumulation of free radical reactive oxygen species for immunotherapy in clinical samples remains a significant challenge. In this study, defect-rich metastable MoS2 nanozymes, i.e., 1T2H-MoS2, are designed via reduction and phase transformation in molten sodium as a guided treatment for human breast cancer. The as-prepared 1T2H-MoS2 exhibited enhanced peroxidase-like activity (≈12-fold enhancement) than that of commercial MoS2, which is attributed to the charge redistribution and electronic state induced by the abundance of S vacancies. The 1T2H-MoS2 nanozyme can function as an extracellular hydroxyl radical generator, efficiently repolarizing TAMs into the M1-like phenotype and directly killing cancer cells. Moreover, the clinical feasibility of 1T2H-MoS2 is demonstrated via ex vivo therapeutic responses in human breast cancer samples. The apoptosis rate of cancer cells is 3.4 times greater than that of cells treated with chemotherapeutic drugs (i.e., doxorubicin).

Single-Pd-Site Catalyst Induced by Different Dimensional Nitrogen of N-Doping Carbon for Efficient Hydroaminocarbonylation of Alkynes.

The unsaturated amides are traditionally synthesized by acylation of carboxylic acids or hydration of nitrile compounds but are rarely investigated by hydroaminocarbonylation of alkynes using heterogeneous single-metal-site catalysts (HSMSCs). Herein, single-Pd-site catalysts supported on N-doping carbon (NC) with different nitrogen dimensions inherited from corresponding metal-organic-framework precursors are successfully synthesized. 2D NC-supported single-Pd-site (Pd1/NC-2D) exhibited the best performance with near 100% selectivity and 76% yield of acrylamide for acetylene hydroaminocarbonylation with better stability, superior to those of Pd1/NC-3D, single-metal-site/nanoparticle coexisting catalyst, and nanoparticle catalyst. The coordination environment and molecular evolution of the single-Pd-site during the process of acetylene hydroaminocarbonylation on Pd1/NC-2D are detailly illuminated by various characterizations and density functional theoretical calculations (DFT). DFT also showed the energy barrier of rate-determining step on Pd1/NC-2D is lower than that of Pd1/NC-3D. Furthermore, Pd1/NC-2D catalyst illustrated the general applicability of the hydroaminocarbonylation for various alkynes.

Strongly-Interacted NiSe2/NiFe2O4 Architectures Built Through Selective Atomic Migration as Catalysts for the Oxygen Evolution Reaction.

The interactions between the catalyst and support are widely used in many important catalytic reactions but the construction of strong interaction with definite microenvironments to understand the structure-activity relationship is still challenging. Here, strongly-interacted composites are prepared via selective exsolution of active NiSe2 from the host matrix of NiFe2O4 (S-NiSe2/NiFe2O4) taking advantage of the differences of migration energy, in which the NiSe2 possessed both high dispersion and small size. The characteristics of spatially resolved scanning transmission X-ray microscopy (STXM) coupled with analytical Mössbauer spectra for the surface and bulk electronic structures unveiled that this strongly interacted composite triggered more charge transfers from the NiSe2 to the host of NiFe2O4 while stabilizing the inherent atomic coordination of NiFe2O4. The obtained S-NiSe2/NiFe2O4 exhibits overpotentials of 290 mV at 10 mA cm-2 for oxygen evolution reaction (OER). This strategy is general and can be extended to other supported catalysts, providing a powerful tool for modulating the catalytic performance of strongly-interacted composites.

Electron Accumulation Induced by Electron Injection-Incomplete Discharge on NiFe LDH for Enhanced Oxygen Evolution Reaction.

Optimizing the local electronic structure of electrocatalysts can effectively lower the energy barrier of electrochemical reactions, thus enhancing the electrocatalytic activity. However, the intrinsic contribution of the electronic effect is still experimentally unclear. In this work, the electron injection-incomplete discharge approach to achieve the electron accumulation (EA) degree on the nickel-iron layered double hydroxide (NiFe LDH) is proposed, to reveal the intrinsic contribution of EA toward oxygen evolution reaction (OER). Such NiFe LDH with EA effect results in only 262 mV overpotential to reach 50 mA cm-2, which is 51 mV-lower compared with pristine NiFe LDH (313 mV), and reduced Tafel slope of 54.8 mV dec-1 than NiFe LDH (107.5 mV dec-1). Spectroscopy characterizations combined with theoretical calculations confirm that the EA near concomitant Vo can induce a narrower energy gap and lower thermodynamic barrier to enhance OER performance. This study clarifies the mechanism of the EA effect on OER activity, providing a direct electronic structure modulation guideline for effective electrocatalyst design.

Midgut membrane protein BmSUH facilitates Bombyx mori nucleopolyhedrovirus oral infection.

Baculoviruses are virulent pathogens that infect a wide range of insects. They initiate infections via specific interactions between the structural proteins on the envelopes of occlusion-derived virions (ODVs) and the midgut cell surface receptors in hosts. However, host factors that are hijacked by baculoviruses for efficient infection remain largely unknown. In this study, we identified a membrane-associated protein sucrose hydrolase (BmSUH) as an ODV binding factor during Bombyx mori nucleopolyhedrovirus (BmNPV) primary infection. BmSUH was specifically expressed in the midgut microvilli where the ODV-midgut fusion happened. Knockout of BmSUH by CRISPR/Cas9 resulted in a significantly higher survival rate after BmNPV orally infection. Liquid chromatography-tandem mass spectrometry analysis and co-immunoprecipitation analysis demonstrated that PIF protein complex required for ODV binding could interact with BmSUH. Furthermore, fluorescence dequenching assay showed that the amount of ODV binding and fusion to the midgut decreased in BmSUH mutants compared to wild-type silkworm, suggesting the role of BmSUH as an ODV binding factor that mediates the ODV entry process. Based on a multilevel survey, the data showed that BmSUH acted as a host factor that facilitates BmNPV oral infection. More generally, this study indicated that disrupting essential protein-protein interactions required for baculovirus efficient entry may be broadly applicable to against viral infection.

Robot-assisted single-port retroperitoneal partial nephrectomy with a novel purpose-built single-port robotic system with deformable surgical instruments.

OBJECTIVE: To investigate the safety and feasibility of using a novel purpose-built single-port robotic system (the SHURUI Robotic Surgical System) with deformable surgical instruments to perform retroperitoneal single-port partial nephrectomy. MATERIALS AND METHODS: A prospective study was conducted to recruit patients with a single renal tumor no more than 4 cm. Robot-assisted single-port partial nephrectomy was performed by using the novel purpose-built single-port robotic system with deformable surgical instruments. Patients' demographics, tumor characteristics, and perioperative parameters were recorded and analyzed. RESULTS: Sixteen patients were recruited to the study. The median tumor size was 2.0 cm (IQR: 1.2-2.4 cm). The median R.E.N.A.L score was 6 (IQR: 4-4.5). In 3 cases, pure single-port surgery was carried out, and all the assistance was through the robotic port. Median docking time was 15.5 min (IQR: 14.25-22.25 min). Median operating time was 148.5 min (IQR: 178-238.5 min). Median console time was 107 min (IQR: 92.75-149.75 min). Median warm ischemic time was 26.5 min (IQR: 24.5-30 min). Median blood loss was 17.5 ml (IQR: 10-50 ml). CONCLUSIONS: Retroperitoneal partial nephrectomy can be safely performed with this novel purpose-built single-port robotic system (SHURUI) with deformable surgical instruments. Further studies are needed to fully evaluate the role of this new platform.

Synthesis of Multisubstituted 2,3-Allenamides via Palladium-Catalyzed Carbonylation of Propargylic Esters.

2,3-Allenamides are an important class of unsaturated group-substituted carbonyl compounds. A palladium-catalyzed aminocarbonylation of propargyl acetates with amines for the synthesized tri-/tetrasubstituted 2,3-allenamides has been developed. A broad range of tri-/tetrasubstituted 2,3-allenamides have been prepared from propargyl acetates in good to excellent yields. The reaction featured mild reaction conditions and good functional group tolerance. The applicability of this methodology was further highlighted by the late-stage modification of several natural products and pharmaceuticals.

Ultrastrong Infrared Emission at 1460 nm from Lanthanide-Doped Nanoparticles with Interfacial Sensitization.

Fluorescent imaging in the second near-infrared window (NIR-II; 1000-1700 nm) has recently received tremendous attention due to its excellent tissue probing depths and high resolution. Under NIR pumping, lanthanide-doped nanoparticles can emit infrared light covering a wide range of 800-3000 nm which has good potential for NIR-II imaging and detection. However, the low efficiency hinders their application. Here, we report intense infrared emission at 1460 nm from lanthanide-doped core/shell nanoparticles with efficient interfacial sensitization. The emitter Tm3+ ion and the sensitizer Yb3+ and Nd3+ ions are spatially separated in core and shells so that the efficient interfacial energy transfer is established between Tm3+ and Yb3+/Nd3+ ions, while thermal vibration spread of high concentration of Yb3+ ions and cross-relaxation among Tm3+, Yb3+, and Nd3+ ions are suppressed. As a result, the ultrastrong NIR-II emission at 1460 nm is achieved, which is more than 100-times that in classic core/shell nanoparticles doped with Tm3+ (NaYF4:20%Yb,0.5%Tm@ NaYF4).

Mechanistic Insights into the Palladium-Catalyzed Perfluoroalkylative Carbonylation of Unactivated Alkenes to ß-Perfluoroalkyl Esters: A DFT Study.

Transition metal-catalyzed multicomponent carbonylation is an efficient synthetic strategy to access multifunctional esters in high yields with broad functional group tolerance and good chemoselectivity. Considering the development of highly efficient synthetic methods for esters, it remains significant to grasp the mechanism of constructing multifunctional esters. Herein, density functional theoretical calculations were carried out to acquire mechanistic insight into the synthesis of ß-perfluoroalkyl esters from a specific palladium-catalyzed perfluoroalkylative carbonylation of unactivated alkenes using carbon monoxide. A detailed mechanistic understanding of this reaction route includes (1) multistep radical reaction process, (2) C-C coupling and CO insertion, (3) ligand exchange, and (4) Pd-based intermediate oxidation and reductive elimination. The multistep radical process was fundamentally rationalized, including Rf· formation and radicals A and E from unactivated alkene and CO oxidation, respectively. The potential energy calculation indicated that the CO insertion into the perfluorinated alkyl radicals preceded Pd-catalyzed oxidation in the competitively multistep free radical reaction process. In addition, the I-/PhO- exchange step was predicted to be spontaneous to products. The IGMH analysis further attested to the reductive elimination process involved in the rate-determining step. Thus, a simple and valid density functional theory (DFT) approach was developed to reveal the multistep radical mechanism for the Pd-catalyzed perfluoroalkylative carbonylation of unactivated alkenes to access functional ß-perfluoroalkyl esters.

Low-frequency repetitive transcranial magnetic stimulation alters the individual functional dynamical landscape.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive approach to modulate brain activity and behavior in humans. Still, how individual resting-state brain dynamics after rTMS evolves across different functional configurations is rarely studied. Here, using resting state fMRI data from healthy subjects, we aimed to examine the effects of rTMS to individual large-scale brain dynamics. Using Topological Data Analysis based Mapper approach, we construct the precise dynamic mapping (PDM) for each participant. To reveal the relationship between PDM and canonical functional representation of the resting brain, we annotated the graph using relative activation proportion of a set of large-scale resting-state networks (RSNs) and assigned the single brain volume to corresponding RSN-dominant or a hub state (not any RSN was dominant). Our results show that (i) low-frequency rTMS could induce changed temporal evolution of brain states; (ii) rTMS didn't alter the hub-periphery configurations underlined resting-state brain dynamics; and (iii) the rTMS effects on brain dynamics differ across the left frontal and occipital lobe. In conclusion, low-frequency rTMS significantly alters the individual temporo-spatial dynamics, and our finding further suggested a potential target-dependent alteration of brain dynamics. This work provides a new perspective to comprehend the heterogeneous effect of rTMS.

The proliferation/migration ability mediated by CD151/PI3K/AKT pathway determines the therapeutic effect of hUC-MSCs transplantation on rheumatoid arthritis.

OBJECTIVE: To elucidate the underlying mechanism by which the proliferation and migration abilities of human umbilical cord mesenchymal stem cells (hUC-MSCs) determine their therapeutic efficacy in rheumatoid arthritis treatment. METHODS: The DBA/1J mice were utilized to establish a collagen-induced RA (CIA) mouse model and to validate the therapeutic efficacy of hUC-MSCs transfected with CD151 siRNA. RNA-seq, QT-PCR and western blotting were utilized to evaluate the mRNA and protein levels of the PI3K/AKT pathway, respectively. RESULTS: IFN-γ significantly enhanced the proliferation and migration abilities of hUC-MSCs, up-regulating the expression of CD151, a gene related to cell proliferation and migration. Effective inhibition of this effect was achieved through CD151 siRNA treatment. However, IFN-γ did not affect hUC-MSCs differentiation or changes in cell surface markers. Additionally, transplantation of CD151-interfered hUC-MSCs (siRNA-CD151-hUC-MSCs) resulted in decreased colonization in the toes of CIA mice and worse therapeutic effects compared to empty vector treatment (siRNA-NC-hUC-MSCs). CONCLUSION: IFN-γ facilitates the proliferation and migration of hUC-MSCs through the CD151/PI3K/AKT pathway. The therapeutic efficacy of siRNA-CD151-hUC-MSCs was found to be inferior to that of siRNA-NC-hUC-MSCs.

Context-Enhanced Network with Spatial-Aware Graph for Smartphone Screen Defect Detection.

Interactive devices such as touch screens have gained widespread usage in daily life; this has directed the attention of researchers to the quality of screen glass. Consequently, defect detection in screen glass is essential for improving the quality of smartphone screens. In recent years, defect detection methods based on deep learning have played a crucial role in improving detection accuracy and robustness. However, challenges have arisen in achieving high-performance detection due to the small size, irregular shapes and low contrast of defects. To address these challenges, this paper proposes CE-SGNet, a Context-Enhanced Network with a Spatial-aware Graph, for smartphone screen defect detection. It consists of two novel components: the Adaptive Receptive Field Attention Module (ARFAM) and the Spatial-aware Graph Reasoning Module (SGRM). The ARFAM enhances defect features by adaptively extracting contextual information to capture the most relevant contextual region of defect features. The SGRM constructs a region-to-region graph and encodes region features with spatial relationships. The connections among defect regions are enhanced during the propagation process through a graph attention network. By enriching the feature representations of defect regions, the CE-SGNet can accurately identify and locate defects of various shapes and scales. Experimental results demonstrate that the CE-SGNet achieves outstanding performance on two public datasets.

The regulatory mechanism of rapid lignification for timely anther dehiscence.

Anther dehiscence is a crucial event in plant reproduction, tightly regulated and dependent on the lignification of the anther endothecium. In this study, we investigated the rapid lignification process that ensures timely anther dehiscence in Arabidopsis. Our findings reveal that endothecium lignification can be divided into two distinct phases. During Phase I, lignin precursors are synthesized without polymerization, while Phase II involves simultaneous synthesis of lignin precursors and polymerization. The transcription factors MYB26, NST1/2, and ARF17 specifically regulate the pathway responsible for the synthesis and polymerization of lignin monomers in Phase II. MYB26-NST1/2 is the key regulatory pathway responsible for endothecium lignification, while ARF17 facilitates this process by interacting with MYB26. Interestingly, our results demonstrate that the lignification of the endothecium, which occurs within approximately 26 h, is much faster than that of the vascular tissue. These findings provide valuable insights into the regulation mechanism of rapid lignification in the endothecium, which enables timely anther dehiscence and successful pollen release during plant reproduction.