BACKGROUND:Because vascular regeneration of diabetic lower limb ischemia (LLI) and prevention of disease progression is a major problem, we explored the molecular mechanism of E2F transcription factor 5 (E2F5) in regulating autophagy to promote angiogenesis in diabetic HLI. METHODS AND RESULTS:The streptozotocin-induced diabetic mice model, hindlimb ischemia (HLI) model and high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs) were constructed for in vivo and in vitro assays. Autophagy inhibitor, 3-methyladenine, reversed the effects of E2F5 overexpression on microtubule-associated protein 1 light chain 3B (LC3B) expression, cell proliferation, migration and tube formation, supporting the involvement of autophagy in E2F5-mediated HUVEC restoration. In vivo injection of E2F5 overexpressed lentivirus also promoted angiogenesis in diabetic HLI mice, concomitant with autophagy activation. Phosphorylated yes-associated protein (pYAP) expression in HUVECs was upregulated after HG treatment and E2F5 overexpression reversed this change. pYAP colocalized with CD31, and pYAP expression was decreased after E2F5 overexpression. Treatment with Ki16425 increased pYAP expression and affected the influence of E2F5 on the proliferation, migration and tubule formation of HUVECs, and LC3B expression. CONCLUSIONS:E2F5 promoted angiogenesis by downregulating pYAP, which is associated with autophagy activation. These findings provide a novel therapeutic strategy for diabetic LLI.

OBJECTIVE:This review aims to elucidate the biological significance of Type H vessels, a specialized bone marrow vascular subtype characterized by high expression of endothelial mucin (Emcn) and PECAM-1/CD31, and their critical role in coupling angiogenesis with osteogenesis. We also discuss their therapeutic potential in craniomaxillofacial trauma and alveolar bone loss. METHODS:This is a narrative review. we identified relevant studies by searching PubMed (MEDLINE) and Web of Science using combinations of keywords related to CD31/Endomucin (Type H Vessels), angiogenic-osteogenic coupling, and oral/craniofacial conditions, and by screening reference lists of key articles. RESULTS:The central role of Type H Vessels in skeletal biology underscores therapeutic promise for mitigating bone loss in periodontitis and other oral pathologies. CONCLUSIONS:Type H Vessels are emerging regulators of angiogenic-osteogenic coupling in skeletal tissues. Although bone and craniofacial tissues are similar and craniofacial evidence is growing, It remains less extensive than long-bone mechanistic studies; therefore, translational strategies in oral medicine should be interpreted in light of this evidence gap. This review consolidates mechanistic and clinical evidence, proposing novel strategies to harness the angiogenic-osteogenic coupling for oral rehabilitation of bone-destructive diseases. Future research should explore precise modulation of Type H Vessels to optimize therapeutic outcomes.

Scarring results in significant developmental, functional, aesthetic, and psychological challenges. Despite substantial demand from patients and healthcare providers, no drugs or biologics are currently approved specifically for preventing or reducing scarring. Our previous studies indicate that fibromodulin (FMOD) modulates adult dermal fibroblasts to adopt fetal-like characteristics, thereby improving wound appearance, reducing scar size, and enhancing tensile strength in adult skin healing. To address the high costs, variability, and safety concerns of producing FMOD through mammalian cells, a novel, chemically synthesized FMOD-derived peptide, SLI-F06, has been developed. SLI-F06 retains FMOD's essential properties, such as promoting cell migration, increasing tensile strength, and stimulating antifibrotic effects. Comprehensive animal studies using models such as mice, rats, Yorkshire pigs (the standard for normal human wound healing), and red Duroc pigs (closely mimicking human proliferative and hypertrophic scarring) demonstrate significant improvements in scar appearance, tensile strength tests, and histological outcomes with SLI-F06. Additionally, a formulation buffer has been developed to maintain physiological pH and osmolality, ensuring the stability of SLI-F06 for a suitable duration in clinical settings after removal from refrigeration. SLI-F06 exhibits no genotoxicity or local or systemic toxicity in extensive studies required by the United States Food and Drug Administration for Investigational New Drug applications.

The role of hydrogen persulfide (H2S2) has remained elusive due to the scarcity of controllable donors, despite its importance as a reactive sulfur species whose dyshomeostasis drives neuroinflammation. Herein, we employed HPD1, a novel esterase-responsive H2S2 donor, to investigate its anti-inflammatory effects and underlying mechanisms in lipopolysaccharide (LPS)-stimulated glial cells. HPD1 alleviated LPS-induced cytotoxicity and promoted a phenotypic shift from a pro-inflammatory and neurotoxic phenotype to an anti-inflammatory and neuroprotective phenotype in microglia (M1 to M2) and primary astrocytes (A1 to A2). Mechanistically, in BV2 microglia, HPD1 significantly inhibited the protein expression of toll-like receptor 4 (TLR4) and attenuated the phosphorylation of key components in the mitogen-activated protein kinase (MAPK) pathway including extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38, and c-Jun N-terminal kinase (JNK). In both BV2 microglia and primary astrocytes, HPD1 effectively suppressed the phosphorylation of both p65 subunit of nuclear factor-κB (NF-κB) and inhibitor of κBα (IκBα), prevented the proteasomal degradation of IκBα, and blocked the nuclear translocation of p65, ultimately attenuating the neuroinflammatory response. Collectively, HPD1 mitigated neuroinflammation by reprogramming glial phenotypic polarization via inhibiting the TLR4-MAPK/NF-κB signaling pathway, elucidating a potential molecular mechanism for H2S2 and suggesting that H2S2 supplementation holds a promising therapeutic strategy for neuroinflammatory diseases.

Abstract Hydrogen persulfide (H 2 S 2 ) is an important endogenous signaling molecule, holding significant therapeutic potential across diverse disease models due to its potent antioxidant and redox-regulating properties. Herein, we report the synthesis, characterization, and in vivo evaluation of an esterase responsive H 2 S 2 donor, HPD1 . It reduced mechanical and cold allodynia at 14 mg/kg (i.p.) in chronic constriction injury and paclitaxel-induced neuropathic pain models. Moreover, HPD1 exhibited negligible systemic toxicity and behavioral side effects even at 28 mg/kg. Electrophysiological tests showed that HPD1 suppressed PTX-induced hyperexcitability in dorsal root ganglion (DRG) neurons by specifically potentiating A-type potassium currents ( I A ). Mechanistically, we demonstrate that HPD1 activates LIMK1, which inactivates cofilin and stabilizes F-actin, thereby promoting the interaction between the actin-binding protein Filamin A and Kv4.2. Furthermore, both the HPD1 -induced increase in Filamin A-Kv4.2 co-localization and the subsequent restoration of I A density in DRG neurons, as well as the analgesic effect of HPD1 were dampened by pharmacological inhibition of LIMK1 with BMS-5. This work has developed a new generation of H 2 S 2 donors, demonstrated the analgesic efficacy of HPD1 , and uncovered the novel LIMK1-cofilin-Filamin A-Kv4.2 dependent mechanism that restores I A , thus providing a reliable therapeutic strategy for neuropathic pain based on H 2 S 2 donors.

Background:Hepatocellular carcinoma (HCC) represents a formidable challenge in oncology, with high mortality rates and limited therapeutic options, particularly for advanced-stage patients. While immunotherapy has shown promise, its efficacy in advanced HCC remains suboptimal, necessitating the exploration of more potent therapeutic strategies. Methods:The HCC cell lines underwent treatment with arsenic sulfide and/or anti-PD1, while HepG2/Hepa1-6 cells were transduced with lentiviruses for THBS1 overexpression or knockdown. The MTT assay, FACS, Western blotting, qRT-PCR, and ChIP were employed to assess proliferation, modulation of proteins and genes. Additionally, C57BL/6J mice were utilized in vivo to investigate the ability of arsenic sulfide to enhance the efficacy of anti-PD-1 therapy. Results:Here, we investigated the role of arsenic sulfide in HCC treatment and explored its potential synergistic effects and underlying mechanisms when combined with immunotherapy. First of all, using bioinformatics analysis and validation in vitro, we identified thrombospondin-1 (THBS1) as a key prognostic factor for HCC in Asian populations. Then, we demonstrated that arsenic sulfide inhibits HCC cell viability, induces apoptosis, and downregulates THBS1 expression. Furthermore, we observed that arsenic sulfide significantly enhances the anti-HCC effects of anti-PD-1 therapy. Mechanistic insights indicate that arsenic sulfide inhibits STAT3 phosphorylation, reduces THBS1 transcription, thereby disrupting the binding between tumor cell THBS1 and T cell CD47, consequently enhancing anti-PD-1 efficacy. Therefore, arsenic sulfide augments anti-PD-1 efficacy against HCC by inhibiting the STAT3-THBS1/CD47 pathway. Conclusions:Collectively, our findings elucidate the role of arsenic sulfide in conjunction with PD - 1 in HCC eradication and its underlying molecular mechanism, providing a precise scientific rationale and a robust theoretical basis for arsenic sulfide's application in HCC treatment.

BackgroundAnti-CD19 chimeric antigen receptor T (CAR-T) cell therapy has proven effective for treating relapsed or refractory acute B cell leukemia. However, challenges such as cytokine release syndrome, T cell dysfunction, and exhaustion persist. Enhancing CAR-T cell efficacy through changing CAR internalization and recycling is a promising approach. The transmembrane domain is the easiest motif to optimize for modulating CAR internalization and recycling without introducing additional domains, and its impact on CAR internalization and recycling has not yet been thoroughly explored. In this study, we aim to enhance CAR-T cell function by focusing on the solely transmembrane domain design.MethodsUtilizing plasmid construction and lentivirus generation, we get two different transmembrane CAR-T cells [19CAR-T(1a) and 19CAR-T(8α)]. Through co-culture with tumor cells, we evaluate CAR dynamic change, activation levels, exhaustion markers, mitochondrial function, and differentiation in both CAR-T cells. Furthermore, immunofluorescence microscopy analysis is performed to reveal the localization of internalized CAR molecules. RNA sequencing is used to detect the transcriptome of activated CAR-T cells. Finally, a mouse study is utilized to verify the anti-tumor efficacy of 19CAR-T(1a) cells in vivo.ResultsOur findings demonstrate that 19CAR-T(1a) has lower surface CAR expression, faster internalization, and a higher recycling rate compared to 19CAR-T(8α). Internalized 19CAR(1a) co-localizes more with early and recycling endosomes, and less with lysosomes than 19CAR(8α). These features result in lower activation levels, less cytokine release, and reduced exhaustion markers in 19CAR-T(1a). Furthermore, CAR-T cells with CD1a transmembrane domain also exhibit a superior anti-tumor ability and reduced exhaustion in vivo.ConclusionOverall, we demonstrate that the transmembrane domain plays a critical role in CAR-T cell function. An optimized transmembrane domain can alleviate cytokine release syndrome and reduce CAR-T cell exhaustion, providing a direction for CAR design to enhance CAR-T cell function.

Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17’s inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na+/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

Orthodontically induced root resorption (OIRR) is difficult to assess accurately using traditional 2D imaging due to distortion and low sensitivity. While CBCT offers more precise 3D evaluation, manual segmentation remains labor-intensive and prone to variability. Recent advances in deep learning enable automatic, accurate tooth segmentation from CBCT images. This study applies deep learning and CBCT technology to quantify OIRR and analyze its risk factors, aiming to improve assessment accuracy, efficiency, and clinical decision-making. This study retrospectively analyzed CBCT scans of 108 orthodontic patients to assess OIRR using deep learning-based tooth segmentation and volumetric analysis. Statistical analysis was performed using linear regression to evaluate the influence of patient-related factors. A significance level of p < 0.05 was considered statistically significant. Root volume significantly decreased after orthodontic treatment (p < 0.001). Age, gender, open (deep) bite, severe crowding, and other factors significantly influenced root resorption rates in different tooth positions. Multivariable regression analysis showed these factors can predict root resorption, explaining 3

Activated myofibroblasts deposit extracellular matrix material to facilitate rapid wound closure that can heal scarlessly during fetal development. However, adult myofibroblasts exhibit a relatively long life and persistent function, resulting in scarring. Thus, understanding how fetal and adult tissue regeneration differs may serve to identify factors that promote more optimal wound healing in adults with little or less scarring. We previously found that matricellular proteoglycan fibromodulin is one such factor promoting more optimal repair, but the underlying molecular and cellular mechanisms for these effects have not been fully elucidated. Here, we find that fibromodulin induces myofibroblast apoptosis after wound closure to reduce scarring in small and large animal models. Mechanistically, fibromodulin accelerates and prolongs the formation of the interleukin 1β-interleukin 1 receptor type 1-interleukin 1 receptor accessory protein ternary complex to increase the apoptosis of myofibroblasts and keloid- and hypertrophic scar-derived cells. As the persistence of myofibroblasts during tissue regeneration is a key cause of fibrosis in most organs, fibromodulin represents a promising, broad-spectrum anti-fibrotic therapeutic.

The nuclear factor of activated T cells 3 (NFATc3) plays a significant role in various cancer-related processes, but its interactions with transcriptional modulators, particularly Promyelocytic Leukemia protein (PML), remain poorly understood. PML, a nuclear scaffold protein, is involved in tumor suppression and transcriptional regulation. This study investigates the interaction between NFATc3 and PML, focusing on the role of SUMOylation and its impact on downstream target genes. In vitro experiments, including mass spectrometry and Co-immunoprecipitation (Co-IP), were conducted to explore this interaction. Additionally, constructs with lysine-to-arginine (K→R) mutations at key SUMOylation sites were generated to determine whether PML SUMOylation is necessary for its interaction with NFATc3. We also assessed the impact of NFATc3 SUMOylation on its binding to PML. Chromatin immunoprecipitation (ChIP) and quantitative real-time PCR (qRT-PCR) were employed to measure the expression of downstream genes (Lgr5 and Olfm4) under NFATc3 and PML overexpression or knockdown conditions. Pharmacological treatment with arsenic sulfide (As4S4) was used to further investigate modulation of the PML-NFATc3 axis. Our findings revealed that the NFATc3-PML interaction is independent of the SUMOylation status of PML. Additionally, mutations in NFATc3 SUMOylation sites did not affect its binding to PML. The PML-NFATc3 axis regulates Lgr5 and Olfm4 expression, and co-expression of NFATc3 and PML synergistically upregulated these genes. Arsenic sulfide treatment reduced this synergistic effect, indicating its potential as a modulator. This study provides new insights into the regulatory mechanisms of NFATc3 and PML, suggesting potential therapeutic targets in cancer.

INTRODUCTION:Distraction osteogenesis has been the preferred treatment modality for patients with hemifacial microsomia. Although an immediate improvement in facial asymmetry is noted at the completion of the procedure, long-term data regarding postdistraction stability is rare. In this study, a ≥12-year follow-up was conducted on patients who underwent distraction osteogenesis to examine the long-term stability of the surgical procedure. This study aimed to evaluate the cephalometric distraction relapse tendency after ≥12 years. METHODS:Three patients with hemifacial microsomia who underwent distraction osteogenesis were recalled, and their records were taken. Multiple measurements, such as mandibular length, ramus height, maxillary height, occlusal height, and chin position, were made to record the changes in the mandible and maxilla from posteroanterior and 45° lateral oblique cephalograms after ≥12 years. RESULTS:Mandibular length, ramus height, maxillary height, chin deviation, occlusal cant, and the interantegonial plane angle showed immediate improvements after distraction. After ≥12 years of distraction, the mandibular length, maxillary height, and occlusal height remained relatively stable, but the ramus height and chin deviation were unstable, resulting in an increase in facial asymmetry. CONCLUSIONS:A combination of decreased growth and postsurgical relapse on the affected side contributes to the continuous worsening of facial asymmetry. Dentoalveolar remodeling contributed to even more facial asymmetry into adulthood. Thus, overcorrection was needed to reduce and overcome the degree of long-term facial asymmetry after growth completion.

Engineered extracellular vesicles (EVs) represent a promising therapeutic strategy with many applications in cancer therapy. EVs derived from engineered tumor-targeting killer cells, such as chimeric antigen receptor (CAR)-T cells. However, the application of CAR-T-EVs is limited by several drawbacks. This study shows that engineered EVs with potent cancer-targeting and killing abilities can be generated from easily manipulable non-killer cells, providing a solution to overcome the limitations of CAR-T-EVs. It is found that EVs derived from non-killer cells such as CD19-targeting 293 cells possess target cell killing capacities comparable to those derived from CD19-CAR-T cells. A technique is developed to ensure the presence of sufficient targeting modules on the EV surface using a chimeric CD8-CD63/CD81 transmembrane region. Uptake of CD19-targeting EVs by target cells can be optimized by switching the route of CD19 endocytosis from clathrin-mediated endocytosis (CME) to aggregation-dependent endocytosis (ADE), leading to lysosomal degradation of the CD19/EVs complex. Degradation of the EVs leads to impairment in the IFN response and subsequent enhancement in EV uptake by target cells, creating a potent feedback cycle. CD19 depletion results in the disruption of the CD19-AKT-Myc pathway in the target cells, enhancing the killing capacity both in vitro and in vivo.

Multifunctional therapeutics have emerged as a solution to the constraints imposed by drugs with singular or insufficient therapeutic effects. The primary challenge is to integrate diverse pharmacophores within a single-molecule framework. To address this, we introduced DeepSA, a novel edit-based generative framework that utilizes deep simulated annealing for the modification of articaine, a well-known local anesthetic. DeepSA integrates deep neural networks into metaheuristics, effectively constraining molecular space during compound generation. This framework employs a sophisticated objective function that accounts for scaffold preservation, anti-inflammatory properties, and covalent constraints. Through a sequence of local editing to navigate the molecular space, DeepSA successfully identified AT-17, a derivative exhibiting potent analgesic properties and significant anti-inflammatory activity in various animal models. Mechanistic insights into AT-17 revealed its dual mode of action: selective inhibition of NaV1.7 and 1.8 channels, contributing to its prolonged local anesthetic effects, and suppression of inflammatory mediators via modulation of the NLRP3 inflammasome pathway. These findings not only highlight the efficacy of AT-17 as a multifunctional drug candidate but also highlight the potential of DeepSA in facilitating AI-enhanced drug discovery, particularly within stringent chemical constraints.

Mixed-dimensional heterostructures provide additional freedom to construct diverse functional electronic and optoelectronic devices, gaining significant interest. Herein, highly-aligned pseudo-1D tellurium is epitaxially grown on 2D monolayer transition metal dichalcogenides (TMDs), including MoSe2, MoS2, and WS2. A one-pot chemical vapor deposition (CVD) technique eliminates the normally required transfer steps, thereby producing mixed-dimensional heterostructures with an ultraclean interface. The controllable epitaxial growth of Te/TMD heterostructures are verified by Raman, scanning probe microscopy (SPM), and transmission electron microscopy (TEM) observation. The photoluminescence results indicate that the emission from TMDs is quenched in the heterostructure, confirming the efficient transfer of photogenerated carriers from TMDs to Te. Additionally, the mixed-dimensional p-n Te/MoSe2 heterojunction photodetector presents self-driven behavior with high responsivity (328 mA W-1), external quantum efficiency (79%), and specific detectivity (8.2 x 10(9) Jones). The modified facile synthesis strategy and proposed growth mechanism in this study shed light on synthesizing mixed-dimensional heterojunctions. This opens avenues for fabricating functional devices with reduced sizes and high densities, further enabling miniaturization and integration opportunities.

Abstract Ferroptosis plays a vital role in the pathological process of numerous human diseases, including cancer. It is possible that ferroptosis stimulation could be used as a cancer treatment strategy. Due to this, ferroptosis-inducing drugs are gaining more attention for the clinical treatment of tumors. For the first time, we demonstrated that arsenic sulfide (As4S4) initiated ferroptotic cell death in hepatocellular carcinoma (HCC) cells, which was concomitant with ROS accumulation, lipid peroxidation, and GSH depletion. Arsenic sulfide -mediated cell death in HCC cells was blocked by ferroptosis inhibitors ferrostatin-1 (Fer-1) and deferoxamine (DFO, an iron chelator), but not Z-VAD-FMK, necrosulfonamide, or chloroquine, suggesting that ferroptosis participated in arsenic sulfide -induced cell death. Transient receptor potential channel 6 (TRPC6) expression was notably inhibited under arsenic sulfide intervention and the overexpression of TRPC6 rescued the effects of arsenic sulfide on ferroptosis. Furthermore, glutathione peroxidase 4 (GPX4), was identified to interact with TRPC6 through confocal microscopy images and co-immunoprecipitation assay. In summary, arsenic sulfide exerts anticancer effects on HCC in vitro and in vivo by inducing ferroptosis via inhibiting TRPC6/GPX4 pathway. Our findings led us to conclude that arsenic sulfide could be considered as a prospective drug for liver cancer treatment.

Osteoblasts (OBs), which are a crucial type of bone cells, derive from bone marrow mesenchymal stem cells (MSCs). Accumulating evidence suggests inflammatory cytokines can inhibit the differentiation and proliferation of OBs, as well as interfere with their ability to synthesize bone matrix, under inflammatory conditions. NLRP3 inflammasome is closely associated with cellular pyroptosis, which can lead to excessive release of pro-inflammatory cytokines, causing tissue damage and inflammatory responses, however, the comprehensive roles of NLRP3 inflammasome in OBs and their differentiation have not been fully elucidated, making targeting NLRP3 inflammasome approaches to treat diseases related to OBs uncertain. In this review, we provide a summary of NLRP3 inflammasome activation and its impact on OBs. We highlight the significant roles of NLRP3 inflammasome in regulating OBs differentiation and function. Furthermore, current available strategies to affect OBs function and osteogenic differentiation targeting NLRP3 inflammasome are listed and analyzed. Finally, through the prospective discussion, we seek to provide novel insights into the crucial role of NLRP3 inflammasome in diseases related to OBs and offer valuable information for devising treatment strategies.

The metal-semiconductor interface fabricated by conventional methods often suffers from contamination, degrading transport performance. Herein, we propose a one-pot chemical vapor deposition (CVD) process to create a two-dimensional (2D) MoO2-MoSe2 heterostructure by growing MoO2 seeds under a hydrogen environment, followed by depositing MoSe2 on the surface and periphery. The ultraclean interface is verified by cross-sectional scanning transmission electron microscopy and photoluminescence. Along with the high work function of semimetallic MoO2 (E-f = -5.6 eV), a high-rectification Schottky diode is fabricated based on this heterostructure. Furthermore, the Schottky diode exhibits an excellent photovoltaic effect with a high open-circuit voltage of 0.26 eV and ultrafast photoresponse, owing to the naturally formed metal-semiconductor contact with suppressed pinning effect. Our method paves the way for the fabrication of an ultraclean 2D metal-semiconductor interface, without defects or contamination, offering promising prospects for future nanoelectronics.

Van der Waals junctions hold significant potentials for various applications in multifunctional and low-power electronics and optoelectronics. The multistep device fabrication process usually introduces lattice mismatch and defects at the junction interfaces, which deteriorate device performance. Here the layer engineering synthesis of van der Waals homojunctions consisting of 2H-MoTe2 with asymmetric thickness to eliminate heterogenous interfaces and thus obtain clean interfaces is reported. Experimental results confirm that the homostructure nature gives rise to the formation of pristine van der Waals junctions, avoiding chemical disorders and defects. The ability to tune the energy bands of 2H-MoTe2 continuously through layer engineering enables the creation of adjustable built-in electric field at the homojunction boundaries, which leads to the achievement of self-powered photodetection based on the obtained 2H-MoTe2 films. Furthermore, the successful integration of 2H-MoTe2 homojunctions into an image sensor with 10 × 10 pixels, brings about zero-power consumption and near-infrared imaging functions. The pristine van der Waals homojunctions and effective integration strategies shed new insights into the development of large-scale application for two-dimensional materials in advanced electronics and optoelectronics.