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Charge density wave (CDW) material 1 T -TaS 2 was proposed as a quantum spin liquid candidate, on which a cluster Mott insulator comes into being below the transition temperature. We report an experimental ultrafast generation and detection of the coherent amplitude mode (AM) of its CDW state. A salient feature emerges: The coherent CDW mode AM exhibits an unusual T 3.56 temperature dependence below 65 K, in addition to the T 2 temperature dependence observed in the 65 to 200 K range. This behavior suggests the enhancement of in-gap electronic excitations below 65 K and the emergence of a new phase of matter. Consequently, the intriguing quantum state leads to a crossover. Our investigation provides insights into understanding the interplay among various degrees of freedom in quantum materials., Competing Interests: Competing interests statement:The authors declare no competing interest.

Transition metal carbides, nitrides, and carbonitrides (MXenes) have attracted great interest in all-optical modulation applications due to their excellent nonlinear optical properties. Herein, we investigated the spatial self-phase modulation (SSPM) of Ti 3 CN flake suspension at wavelengths ranging from 405 to 1064 nm. Broadband third-order nonlinear optical susceptibility χ (3) values of Ti 3 CN were found to be ∼10 -9 e.s.u. (5.35 × 10 -9 e.s.u. at 532 nm), which was 3 to 5 times greater than those of transition metal dichalcogenides. In particular, Ti 3 CN exhibited a faster nonlinear optical response time (0.36 s) in the near-infrared region than that in the visible regime (0.4 to 0.53 s), with the response time increasing with wavelength in the visible regime. Our study reveals that Ti 3 CN can serve as a potential candidate for applications in nonlinear optical devices, especially for near-infrared all-optical devices.

Hepatocellular carcinoma (HCC) represents a significant health concern. Identifying novel molecular targets is crucial for clinical diagnosis and targeted treatment of HCC. Aptamers are capable of binding specifically to cancer cells via target protein molecules. Consequently, aptamers are frequently employed to identify novel cancer biomarkers. The invasiveness of tumor cells is closely associated with the recurrence and metastasis of tumors. In this study, the highly invasive Huh7-P3 cells were initially constructed, and subsequently, several aptamers that could specifically recognize Huh7-P3 were developed using cell-based Systematic Evolution of Ligands by Exponential Enrichment (SELEX). The selected aptamer, designated S2-2, demonstrated the capacity to bind to multiple cancer cells. Furthermore, tissue imaging demonstrated that S2-2 exhibited a specific recognition of HCC tissue, while demonstrating no binding to normal tissue. Subsequently, voltage-dependent anion channel 1 (VDAC1) was identified as a potential target for S2-2. Furthermore, Doxorubicin (Dox)-loaded S2-2 was shown to specifically kill target Huh7-P3 cells. In vivo fluorescence imaging revealed that S2-2 was capable of specifically targeting tumors. Importantly, S2-2-Dox enhanced the anti-tumor efficacy of Dox in cell-line-derived xenograft (CDX) model. This study may provide a promising biomarker and molecular target for the clinical diagnosis and targeted therapy of cancers with high VDAC1 expression., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jing Lu reports financial support was provided by National Natural Science Foundation of China (81572972). Jing Lu reports financial support was provided by Key Research Program of Higher Education Institutions in Henan Province (24A310020). Jing Lu reports National Talent Cultivation Programme for First-class Disciplines of Clinical Medicine at Zhengzhou University School of Medicine. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Hybrid excitons formed via resonant hybridization in 2D material heterostructures feature both large optical and electrical dipoles, providing a promising platform for many-body exciton physics and correlated electronic states. However, hybrid excitons at organic-inorganic interface combining the advantages of both Wannier-Mott and Frenkel excitons remain elusive. Here, hybrid excitons are reported in the copper phthalocyanine/molybdenum diselenide (CuPc/MoSe 2 ) heterostructure (HS) featuring strong molecular orientation dependence by low-temperature photoluminescence and absorption spectroscopy. The hybrid Wannier-Mott-Frenkel excitons exhibit a large oscillator strength and display signatures of the Frenkel excitons in CuPc and the Wannier-Mott excitons in MoSe 2 simultaneously through the delocalized electrons. The density functional theory (DFT) calculations further confirm the strong hybridization between the lowest unoccupied molecular orbital (LUMO) of CuPc and the conduction band minimum (CBM) of MoSe 2 . The out-of-plane molecular orientation is further employed to tune the hybridization strength and tailor the hybrid exciton states. The results reveal the hybrid excitons at the CuPc/MoSe 2 interface with tunability by molecular orientation, suggesting that the organic-inorganic HS constitutes a promising platform for many-body exciton physics such as exciton condensation and optoelectrical applications., (© 2025 Wiley‐VCH GmbH.)

Transition metal phosphorus sulfides (MPS 3 ), a family of two-dimensional magnetic materials with a van der Waals structure, exhibit promising applications in nonlinear optical devices. The emergence of carrier coherence in MPS 3 is a fascinating topic in coherently controlling the nonlinear effect (or other novel phenomena). Herein, we systematically investigated the third-order nonlinear optical responses of MPS 3 (M = Ni, Fe, Mn) flake suspensions based on spatial self-phase modulation (SSPM) effect. The effective monolayer third-order nonlinear susceptibilities ( χ monolayer(3)) of NiPS 3 and MnPS 3 are obtained for the first time at multiple wavelengths. Our results show that NiPS 3 has a higher χ monolayer(3) value (3.59 × 10 -9 e.s.u. or 5.01 × 10 -17 m 2 V -2 at 405 nm excitation) than those of FePS 3 and MnPS 3 . Furthermore, we laser-induced non-local hole coherence in MPS 3 based on SSPM, where the origin of excited-state holes is analyzed from electronic structures. The relationships between hole mobility μ hole , effective mass m h ∗, and χ monolayer(3) for the three materials fulfill the previous investigation results. Because laser-induced hole coherence has rarely been reported, our investigation enriches the coherent regulation of two-dimensional magnetic MPS 3 materials, enabling potential applications in all-optical devices.

Whether soil heavy metal pollution contributes to the decline in pollinator populations remains inconclusive. Based on the detection of heavy metals in the nectar, pollen, and bodies of pollinating insects in areas affected by heavy metal pollution, this study aimed to investigate the impact of adding four heavy metals-zinc (Zn), lead (Pb), copper (Cu), and nickel (Ni)-at realistic concentrations to the diet on the pre-oviposition period, larval development period, production of adult bees, and weight of worker bees. The study sought to evaluate the influence of heavy metal accumulation mediated by floral rewards on key stages of growth and development of bumblebee (Bombus terrestris L.). Results revealed that Zn, Pb, and Cu significantly extended the pre-oviposition period of queen bees, with Pb doubling the time at high concentrations and Ni showing no significant effect at moderate to low concentrations. Lead, Cu, and Ni significantly extended the larval development period at medium and high concentrations, whereas Zn only had a significant effect at high concentrations. The four heavy metals significantly reduced the adult bee yield and the body weight of worker bees at different concentrations, among which the high concentrations of Pb and Cu significantly reduced the adult bee yield by 25%-40%. The effect of a high concentration of copper on the body weight of worker bees was the most obvious, a reduction by 30%. Our findings support the hypothesis that heavy metal pollution, mediated by floral rewards, can have serious impact on some key stages of growth and development of bumblebees., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Society of Environmental Toxicology and Chemistry. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The increasing demand for denser information storage and faster data processing has fueled a keen interest in exploring spin currents up to terahertz (THz) frequencies. Emergent 2D intrinsic magnetic materials constitute a novel and highly controllable platform to access such femtosecond spin dynamics at atomic layer thickness. However, the function of 2D van der Waals magnets are limited by their Curie temperatures, which are usually low. Here, in a 2D superlattice (Fe 3 GeTe 2 /CrSb) 3 , we demonstrate ultrafast laser-induced spin current generation and THz radiation at room temperature, overcoming the challenge of the Curie temperature of Fe 3 GeTe 2 being only 206 K. In tandem with time-resolved magneto-optical Kerr effect measurements and first-principles calculations, we further elucidate the origin of the spin currents-a laser-enhanced proximity effect manifested as a laser-induced reduction of interlayer distance and enhanced electron exchange interactions, which causes transient spin polarization in the heterostructure. Our findings present an innovative, magnetic-element-free route for generating ultrafast spin currents within the 2D limit, underscoring the significant potential of laser THz emission spectroscopy in investigating laser-induced extraordinary spin dynamics., (© The Author(s) 2024. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Recently, tremendous research interest has been aroused in clathrate superhydrides. However, their microscopic properties, especially the superconducting (SC) gap and electron-phonon coupling (EPC) strength, are largely unexplored experimentally. Here, we investigate the time-resolved ultrafast spectroscopy of a superconductor LaH 10±δ under an ultrahigh pressure of 165 GPa. By analyzing the ultrafast dynamics of the quasiparticles, we experimentally obtain the SC gap Δ(0) = 53 ± 5 meV, revealing a gap ratio 2Δ(0)/k B T c  = 5.6 and a gap parameter ϑ = 1.95. Significantly, we experimentally estimate λ ⟨ Ω 2 ⟩  = (2.4 ± 0.1) × 10 4 (meV) 2 , which corresponds to an EPC strength λ = 2.58 ± 0.11. These results together provide direct experimental evidence that strong EPC is responsible for the near-room-temperature superconductivity in clathrate superhydrides. Our investigation significantly advances the experimental exploration of superhydrides, and contributes to the ultrafast dynamics investigations of quantum materials under high pressures., (© 2024. The Author(s).)

Ubiquitin-specific protease 4 (USP4) has been identified as a promising oncogenic factor implicated in various human malignancies. However, the exact biological functions and underlying mechanisms of USP4 in the progression of papillary thyroid carcinoma (PTC) remain elusive. In this study, we observed a marked upregulation of USP4 expression in PTC tumor tissues. Elevated levels of USP4 were significantly correlated with aggressive clinicopathological features and poor prognosis. Functional assays for loss-of-function demonstrated that silencing USP4 hindered the proliferation of PTC cells. Furthermore, our investigation revealed a specific interaction between USP4 and lactate dehydrogenase A (LDHA), wherein USP4 played a crucial role in stabilizing LDHA protein levels via deubiquitination in PTC cells. Notably, this study demonstrated that USP4 promotes PTC proliferation by modulating the MAPK and AKT signaling pathways. In summary, our findings elucidate the critical involvement of the USP4/LDHA axis in driving PTC progression through the modulation of MAPK and AKT pathways, thereby identifying USP4 as a potential therapeutic target for the treatment of PTC.

Novel therapeutic targets and their inhibitors for esophageal squamous cell carcinoma (ESCC) prevention and therapy are urgently needed. This study aimed to investigate the function of DEAD-box helicase 5 (DDX5) in ESCC progression and to identify a promising inhibitor of DDX5. We verified that DDX5 was highly expressed in ESCC and played an oncogenic role, binding with vav guanine nucleotide exchange factor 3 (VAV3) mRNA and facilitating VAV3 mRNA N6-methyladenosine (m6A) modification by interacting with the m6A methyltransferase 3 (METTL3). M6A-modified VAV3 mRNA was identified by insulin-like growth factor 1 (IGF2BP1), increasing mRNA stability. Methylnissolin-3-β-D-O-glucoside (MD) inhibited ESCC progression through the DDX5-VAV3 axis. Our findings suggest that DDX5 promotes ESCC progression. MD inhibits ESCC progression by targeting DDX5., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Competing Interests: The authors declare no competing interests.

Background: Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of digestive system tumor related death in the world. Unfortunately, effective chemopreventive agent is lack for patients with ESCC in clinical practice, which leads to the extremely high mortality rate., Methods: A library of prescribed drugs was screened for finding critical anti-tumor properties in ESCC cells. The phosphoproteomics, kinase array, pulldown assay and drug affinity responsive target stabilization assay (DARTS) were applied to explore mechanisms and searched for synergistic targets. Established models of PDX in mice were used to determine the therapeutic effect of domperidone., Results: After screening a library of prescribed drugs, we discovered that domperidone has anti-tumor properties. Domperidone, acting as a gastroprokinetic agent, has been widely used in clinic for gastrointestinal motility disorders. Despite limited research, there are indications that domperidone may have anti-tumor properties. In this study, we determined that domperidone significantly inhibited ESCC proliferation in vitro and in vivo. We employed phosphoproteomics to reveal p-ERK, and p-SMAD3 down-regulation upon domperidone treatment. Then, the results of kinase assay and pulldown assay further validated that domperidone directly combined with MEK1/2 and CDK4, leading to the inhibition of their kinase activity. Furthermore, our results revealed that MEK/ERK and CDK4/SMAD3 signal pathway were major pathways in domperidone against ESCC., Conclusion: Collectively, these findings suggest that domperidone serves as an effective "multi-target" inhibitor of MEK1/2 and CDK4, offering potential benefits for the chemoprevention of ESCC., (© 2024. The Author(s).)

Tumor cell-targeting molecules play a vital role in cancer diagnosis, targeted therapy, and biomarker discovery. Aptamers are emerging as novel targeting molecules with unique advantages in cancer research. In this work, we have developed several DNA aptamers through cell-based systematic evolution of ligands by exponential enrichment (Cell-SELEX). The selected SYL-6 aptamer can bind to a variety of cancer cells with high signal. Tumor tissue imaging demonstrated that SYL-6-Cy5 fluorescent probe was able to recognize multiple clinical tumor tissues but not the normal tissues, which indicates great potential of SYL-6 for clinical tumor diagnosis. Meanwhile, we identified prohibitin 2 (PHB2) as the molecular target of SYL-6 using mass spectrometry, pull-down and RNA interference assays. Moreover, SYL-6 can be used as a delivery vehicle to carry with doxorubicin (Dox) chemotherapeutic agents for antitumor targeted chemotherapy. The constructed SYL-6-Dox can not only selectively kill tumor cells in vitro, but also inhibit tumor growth with reduced side effects in vivo. This work may provide a general tumor cell-targeting molecule and a potential biomarker for cancer diagnosis and targeted therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Patients with colorectal cancer (CRC) suffer from poor prognosis and lack effective drugs. Dihydroartemisinin (DHA) has anti-cancer potential but the mechanism remains unclear. We elucidated the effects and mechanism of DHA on CRC development with the aim of providing an effective, low-toxicity drug and a novel strategy for CRC. Herein, proliferation assay, transwell assay, tube formation assay, metastasis models, PDX model and AOM/DSS model were used to reveal the effects of DHA on CRC. The key pathway and target were identified by RNA-seq, ChIP, molecular docking, pull down and dual-luciferase reporter assays. As a result, DHA showed a strong inhibitory effect on the growth, metastasis and angiogenesis of CRC with no obvious toxicity, and the inhibitory effect was similar to that of the clinical drug Capecitabine (Cap). Indeed, DHA directly targeted GSK-3β to inhibit CRC development through the GSK-3β/TCF7/MMP9 pathway. Meaningfully, DHA in combination with Cap enhanced the anti-cancer effect, and alleviated Cap-induced diarrhoea, immunosuppression and inflammation. In conclusion, DHA has the potential to be an effective and low-toxicity drug for the treatment of CRC. Furthermore, DHA in combination with Cap could be a novel therapeutic strategy for CRC with improved efficacy and reduced side effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Electron-phonon coupling (EPC) and phonon-phonon scattering (PPS) are at the core of the microscopic physics mechanisms of vast quantum materials. However, to date, there are rarely reports that these two processes can be spatially separated, although they are usually temporally detached with different characteristic lifetimes. Here, by employing ultrafast spectroscopy to investigate the photo-carrier ultrafast dynamics in a LaCoO 3 thin film on a (100) SrTiO 3 substrate, intriguing evidence is found that the two interactions are indeed spatially separated. The EPC mainly occurs in the thin film, whereas PPS is largely in the substrate, especially at the several atomic layers near the interface. Across-interface penetration and decay of optical phonons into acoustic phonons thus naturally occur. An EPC strength λ Eg  = 0.30 is also obtained and an acoustic phonon mode at 45.3 GHz is observed. The finding lays out a cornerstone for future quantum nano device designs., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: Esophageal squamous cell carcinoma (ESCC) is an aggressive and deadly malignancy characterized by late-stage diagnosis, therapy resistance, and a poor 5-year survival rate. Finding novel therapeutic targets and their inhibitors for ESCC prevention and therapy is urgently needed., Methods: We investigated the proviral integration site for maloney murine leukemia virus 3 (Pim-3) protein levels using immunohistochemistry. Using Methyl Thiazolyl Tetrazolium and clone formation assay, we verified the function of Pim-3 in cell proliferation. The binding and inhibition of Pim-3 by corynoline were verified by computer docking, pull-down assay, cellular thermal shift assay, and kinase assay. Cell proliferation, Western blot, and a patient-derived xenograft tumor model were performed to elucidate the mechanism of corynoline inhibiting ESCC growth., Results: Pim-3 was highly expressed in ESCC and played an oncogenic role. The augmentation of Pim-3 enhanced cell proliferation and tumor development by phosphorylating mitogen-activated protein kinase 1 (MAPK1) at T185 and Y187. The deletion of Pim-3 induced apoptosis with upregulated cleaved caspase-9 and lower Bcl2 associated agonist of cell death (BAD) phosphorylation at S112. Additionally, binding assays demonstrated corynoline directly bound with Pim-3, inhibiting its activity, and suppressing ESCC growth., Conclusions: Our findings suggest that Pim-3 promotes ESCC progression. Corynoline inhibits ESCC progression through targeting Pim-3., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignant tumor of the digestive tract with a low 5-year survival rate due to the lack of effective treatment methods. Although therapeutic monoclonal antibodies (mAbs) now play an important role in cancer therapy, effective targeted mAbs are still lacking for ESCC. B7-H3 is highly expressed in a variety of tumors and has emerged as a promising therapeutic target. Several mAbs against B7-H3 have advanced to clinical trials, but their development has not yet been pursued for ESCC. Here, we developed a humanized and Fc-engineered anti-B7H3 mAb 24F-Hu-mut2 and systematically evaluated its anti-tumor activity in vitro and in vivo . The 24F-Hu-mut2 was humanized and modified in Fc fragment to obtain stronger antibody-dependent cell-mediated cytotoxicity(ADCC) activity and nanomolar affinity. Furthermore, both of ESCC cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mice models indicated that 24F-Hu-mut2 displayed potent in vivo anti-tumor activity. In addition, a computational docking model showed that the mAb bound to IgC1 and IgC2 domain of B7-H3, which is closer to the cell membrane. Consistently, our ELISA results verified the binding of 24F-Hu-WT and IgC1 and IgC2. Our results indicate that 24F-Hu-mut2 has significant anti-ESCC activity both in vitro and in vivo , and this monoclonal antibody may be a promising antibody against ESCC and other B7-H3 overexpressing tumors., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Colorectal cancer (CRC) is a highly aggressive cancer in which metastasis plays a key role. However, the mechanisms underlying metastasis have not been fully elucidated. Peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), a regulator of mitochondrial function, has been reported as a complicated factor in cancer. In this study, we found that PGC-1α was highly expressed in CRC tissues and was positively correlated with lymph node and liver metastasis. Subsequently, PGC-1α knockdown was shown to inhibit CRC growth and metastasis in both in vitro and in vivo studies. Transcriptomic analysis revealed that PGC-1α regulated ATP-binding cassette transporter 1 (ABCA1) mediated cholesterol efflux. Mechanistically, PGC-1α interacted with YY1 to promote ABCA1 transcription, resulting in cholesterol efflux, which subsequently promoted CRC metastasis through epithelial-to-mesenchymal transition (EMT). In addition, the study identified the natural compound isoliquiritigenin (ISL) as an inhibitor that targeted ABCA1 and significantly reduced CRC metastasis induced by PGC-1α. Overall, this study sheds light on how PGC-1α promotes CRC metastasis by regulating ABCA1-mediated cholesterol efflux, providing a basis for further research to inhibit CRC metastasis., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

As one of the most essential components of the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) interact extensively with cancer cells and other stromal cells to remodel TME and participate in the pathogenesis of cancer, which earmarked themselves as new promising targets for cancer therapy. Numerous studies have highlighted the heterogeneity and versatility of CAFs in most cancer types. Thus, the identification and appropriate use of CAF-related genes (CAFGenes) in the context of specific cancer types will provide critical insights into disease mechanisms and CAF-related therapeutic targets. In this study, we collected and curated 5421 CAFGenes identified from small- or large-scale experiments, encompassing 4982 responsors that directly or indirectly participate in cancer malignant behaviors managed by CAFs, 1069 secretions that are secreted by CAFs and 281 regulators that contribute in modulating CAFs in human and mouse, which covered 24 cancer types. For these human CAFGenes, we performed gene expression and prognostic marker-based analyses across 24 cancer types using TCGA data. Furthermore, we provided annotations for CAF-associated proteins by integrating the knowledge of protein-protein interaction(s), drug-target relations and basic annotations, from 9 public databases. CAFrgDB (CAF related Gene DataBase) is free for academic research at http://caf.zbiolab.cn and we anticipate CAFrgDB can be a useful resource for further study of CAFs., (© 2023. The Author(s).)

Targeted therapy attempts are needed to enhance esophageal squamous cell carcinoma (ESCC) patients' overall survival and satisfaction of life. Nuclear factor erythroid 2-related factor 2 (NRF2), as a high-confidence cancer driver gene, controls the antioxidant response, metabolic balance and redox homeostasis in cancer and is regarded as a potent molecular target for cancer treatment. Here, we attempted to find a new NRF2 inhibitor and study the underlying molecular mechanism in ESCC. We found that up-regulated NRF2 protein was negatively correlated with patient prognosis and promoted tumor proliferation in ESCC. Moreover, Pizotifen malate (PZM), a FDA-approved medication, bound to the Neh1 domain of NRF2 and prevented NRF2 protein binding to the ARE motif of target genes, suppressing transcription activity of NRF2. PZM treatment suppressed tumor development in ESCC PDX model by inducing ferroptosis via down-regulating the transcription of GPX4, GCLC, ME1 and G6PD. Our study illustrates that the over expression of NRF2 indicates poor prognosis and promotes tumor proliferation in ESCC. PZM, as a novel NRF2 inhibitor, inhibits the tumor growth by inducing ferroptosis and elucidates a potent NRF2-based therapy strategy for patients with ESCC., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway., (© 2022. Higher Education Press.)

Esophageal squamous cell carcinoma (ESCC) accounts for 90% of esophageal cancers and has a high mortality rate worldwide. The 5-year survival rate of ESCC patients in developing countries is <20%. Hence, there is an urgent need for developing new and effective treatments that are based on newly-discovered emerging molecules and pathways to prevent ESCC occurrence and recurrence. We investigated the effects of Daurisoline, a bis-benzylisoquinoline alkaloid extracted from the rhizome of menisperum dauricum, on ESCC cell proliferation and elucidated the molecular mechanisms underlying its functions. To explore the effects of Daurisoline on ESCC growth in vitro and in vivo, cell proliferation assays and anchorage-independent growth assays were performed and a patient-derived xenograft (PDX) model was established. Subsequently, phosphoproteomics, molecular docking analysis, pull down assays, mutation experiments and in vitro kinase assay were performed to explore the mechanism of Daurisoline's function on ESCC. Daurisoline inhibited ESCC proliferation in vitro and reduced ESCC PDX exnograft growth in vivo by reducing ERK1/2 phosphorylation. Furthermore, it directly bound to MEK1 (at Asn78 and Lys97) and MEK2 (at Asp194 and Asp212) kinases to inactivate the ERK1/2 signaling pathway. Our results suggest that Daurisoline is a dual inhibitor of MEK1 and MEK2 and suppresses ESCC growth both in vitro and in vivo by inactivating the ERK1/2 signaling pathway. This is first report on the use of MEK inhibitor for ESCC and highlights its potential applications for ESCC treatment and prevention., (© 2023 The Authors. Molecular Carcinogenesis published by Wiley Periodicals LLC.)

Birefringence, which modulates the polarization of electromagnetic wave, has been commercially developed and widely used in modern photonics. Fostered by high-frequency signal processing and communications, feasible birefringence technologies operating in gigahertz (GHz) range are highly desired. Here, a coherent phonon-induced GHz optical birefringence and its manipulation in SrTiO 3 (STO) crystals are demonsrated. With ultrafast laser pumping, the coherent acoustic phonons with low damping are created in the transducer/STO structures. A series of transducer layers are examined and the optimized one with relatively high photon-phonon conversion efficiency, i.e., semiconducting LaRhO 3 film, is obtained. The most intriguing finding here is that, by virtue of high sensitivity to strain perturbation of STO, GHz optical birefringence can be induced by the coherent acoustic phonons and the birefringent amplitudes possess crystal orientation dependence. Optical manipulation of both coherent phonons and its induced GHz birefringence by double pump technique are also realized. These findings reveal an alternative mechanism of ultrafast optical birefringence control, and offer prospects for applications in high-frequency acoustic-optics devices., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

We demonstrate high-power longwave mid-IR ultrafast sources based on a high-power Er-fiber laser system at 1.55 µm with a 32-MHz repetition rate. Compared with previous 1.03-µm-driven difference frequency generation (DFG), our current configuration allows tighter focusing in the GaSe crystal thanks to an increased damage threshold at 1.55 µm. Consequently, the 1.55-µm-driven DFG can operate in the regime of optical parametric amplification (OPA), in which the mid-IR power grows exponentially with respect to the square root of the pumping power. We experimentally demonstrate this operation regime and achieve broadband mid-IR pulses that are tunable in the 7.7-17.3 µm range with a maximum average power of 58.3 mW, which is also confirmed by our numerical simulation.

Esophageal squamous cell carcinoma (ESCC) is an upper gastrointestinal cancer with high morbidity and mortality. New strategies are urgently needed to prolong patients' survival. Through screening FDA-approved drugs, we found dasabuvir, a drug approved for hepatitis C virus (HCV) treatment, suppressed ESCC proliferation. Dasabuvir could inhibit the growth of ESCC cells in a time and dose-dependent manner and arrested cell cycle at the G0/G1 phase. The antitumor activity was further validated in vivo using patient-derived xenograft tumor models. In terms of mechanism, we unveil that dasabuvir is a Rho-associated protein kinase 1 (ROCK1) inhibitor. Dasabuvir can bind to ROCK1 and suppress its kinase activity, thus downregulating the phosphorylation of ERK1/2 by ROCK1 and the expression of cyclin-dependent kinase 4 (CDK4) and cyclin D1. These results provide evidence that dasabuvir suppresses ESCC growth in vivo and in vitro through blocking ROCK1/ERK signaling pathway., (© 2023. The Author(s).)

Esophageal cancer, especially esophageal squamous cell carcinoma (ESCC), poses a serious threat to human health. It is urgently needed to develop recognition tools and discover molecular targets for early diagnosis and targeted therapy of esophageal cancer. Here, we developed several DNA aptamers that can bind to ESCC KYSE410 cells with a nanomolar range of dissociation constants by using cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX). The selected A2 aptamer is found to strongly bind with multiple cancer cells, including several ESCC cell lines. Tissue imaging displayed that the A2 aptamer can specifically recognize clinical ESCC tissues but not the adjacent tissues. Moreover, we identified integrin β1 as the binding target of A2 through pull-down and RNA interference assays. Meanwhile, molecular docking and mutation assays suggested that A2 probably binds to integrin β1 through the nucleotides of DA16-DG21, and competitive binding and structural alignment assays indicated that A2 shares the overlapped binding sites with laminin and arginine-glycine-aspartate ligands. Furthermore, we engineered A2-induced targeted therapy for ESCC. By constructing A2-tethered DNA nanoassemblies carrying multiple doxorubicin (Dox) molecules as antitumor agents, inhibition of tumor cell growth in vitro and in vivo was achieved. This work provides a useful targeting tool and a potential molecular target for cancer diagnosis and targeted therapy and is helpful for understanding the integrin mechanism and developing integrin inhibitors.

The transmission of satellite payload data is critical for services provided by aerospace ground networks. To ensure the correctness of data transmission, the TCP data transmission protocol has been used typically. However, the standard TCP congestion control algorithm is incompatible with networks with a long time delay and a large bandwidth, resulting in low throughput and resource waste. This article compares recent studies on TCP-based acceleration algorithms and proposes an acceleration algorithm based on the learning of historical characteristics, such as end-to-end delay and its variation characteristics, the arrival interval of feedback packets (ACK) at the receiving end and its variation characteristics, the degree of data packet reversal and its variation characteristics, delay and jitter caused by the security equipment's deep data inspection, and random packet loss caused by various factors. The proposed algorithm is evaluated and compared with the TCP congestion control algorithms under both laboratory and ground network conditions. Experimental results indicate that the proposed acceleration algorithm is efficient and can significantly increase throughput. Therefore, it has a promising application prospect in high-speed data transmission in aerospace-ground service networks.

Recently, ferromagnetic-heterostructure spintronic terahertz (THz) emitters have been recognized as one of the most promising candidates for next-generation THz sources, owing to their peculiarities of high efficiency, high stability, low cost, ultrabroad bandwidth, controllable polarization, and high scalability. Despite the substantial efforts, they rely on external magnetic fields to initiate the spin-to-charge conversion, which hitherto greatly limits their proliferation as practical devices. Here, a unique antiferromagnetic-ferromagnetic (IrMn 3 |Co 20 Fe 60 B 20 ) heterostructure is innovated, and it is demonstrated that it can efficiently generate THz radiation without any external magnetic field. It is assigned to the exchange bias or interfacial exchange coupling effect and enhanced anisotropy. By precisely balancing the exchange bias effect and enhanced THz radiation efficiency, an optimized 5.6 nm-thick IrMn 3 |Co 20 Fe 60 B 20 |W trilayer heterostructure is successfully realized, yielding an intensity surpassing that of Pt|Co 20 Fe 60 B 20 |W. Moreover, the intensity of THz emission is further boosted by togethering the trilayer sample and bilayer sample. Besides, the THz polarization may be flexibly controlled by rotating the sample azimuthal angle, manifesting sophisticated active THz field manipulation capability. The field-free coherent THz emission that is demonstrated here shines light on the development of spintronic THz optoelectronic devices., (© 2022 Wiley-VCH GmbH.)

Gastric cancer (GC) ranks fifth in global incidence and fourth in mortality. The current treatments for GC include surgery, chemotherapy and radiotherapy. Although treatment strategies for GC have been improved over the last decade, the overall five-year survival rate remains less than 30%. Therefore, there is an urgent need to find novel therapeutic or preventive strategies to increase GC patient survival rates. In the current study, we found that tegaserod maleate, an FDA-approved drug, inhibited the proliferation of gastric cancer cells, bound to MEK1/2 and suppressed MEK1/2 kinase activity. Moreover, tegaserod maleate inhibited the progress of gastric cancer by depending on MEK1/2. Notably, we found that tegaserod maleate suppressed tumor growth in the patient-derived gastric xenograft (PDX) model. We further compared the effect between tegaserod maleate and trametinib, which is a clinical MEK1/2 inhibitor, and confirmed that tegaserod maleate has the same effect as trametinib in inhibiting the growth of GC. Our findings suggest that tegaserod maleate inhibited GC proliferation by targeting MEK1/2.

Papillary thyroid carcinomas (PTC) arising from the isthmus have aggressive clinical and pathological features, especially regarding the Delphian lymph node (DLN), which are associated with poor overall and disease-specific survival of patients with head and neck cancer. In the present study, we evaluated clinicopathological characteristics in 195 DLN-positive isthmus PTCs (14.9%) and their lymph node metastatic pattern in 1305 isthmus PTC patients in our hospital between January 2016 and July 2019. Furthermore, a multivariate analysis was conducted to investigate independent risk factors for isthmus PTC with a positive DLN. The results showed that a positive DLN was significantly related to tumour size, extrathyroid extension, median number of DLN, and metastasis to the central, bilateral central, lateral, and pretracheal lymph nodes. Meanwhile, patients with DLN-positive PTC had a significantly increased incidence of suspected preoperative lymph node status than patients with DLN-negative PTC. Multivariate logistic regression of DLN metastasis in PTC located in the isthmus showed that tumour size, extrathyroid extension, and metastasis to the central, bilateral central, lateral, and pretracheal lymph nodes, were independent risk factors., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Due to the high recurrence and low 5-year survival rates of esophageal squamous cell carcinoma (ESCC) after treatment, the discovery of novel drugs for recurrence chemoprevention is of particular importance., Methods: We screened the FDA-approved drug library and found that Nuplazid, an atypical antipsychotic that acts as an effective 5-HT 2 A receptor inverse agonist, could potentially exert anticancer effects in vitro and in vivo on ESCC., Results: Pull-down results indicated that Nuplazid binds with p21-activated kinase 4 (PAK4), and a kinase assay showed that Nuplazid strongly suppressed PAK4 kinase activity. Moreover, Nuplazid exhibited inhibitory effects on ESCC in vivo., Conclusions: Our findings indicate that Nuplazid can suppress ESCC progression through targeting PAK4., (© 2021. The Author(s).)

The search of novel quasi-1D materials is one of the important aspects in the field of material science. Toroidal moment, the order parameter of ferrotoroidic order, can be generated by a head-to-tail configuration of magnetic moment. It has been theoretically proposed that 1D dimerized and antiferromagnetic (AFM)-like spin chain hosts ferrotoroidicity and has the toroidal moment composed of only two antiparallel spins. Here, the authors report a ferrotoroidic candidate of Ba 6 Cr 2 S 10 with such a theoretical model of spin chain. The structure consists of unique dimerized face-sharing CrS 6 octahedral chains along the c axis. An AFM-like ordering at ≈10 K breaks both space- and time-reversal symmetries and the magnetic point group of mm'2'allows three ferroic orders in Ba 6 Cr 2 S 10 : (anti)ferromagnetic, ferroelectric, and ferrotoroidic orders. Their investigation reveals that Ba 6 Cr 2 S 10 is a rare ferrotoroid ic candidate with quasi 1D spin chain, which can be considered as a starting point for the further exploration of the physics and applications of ferrotoroidicity., (© 2022 Wiley-VCH GmbH.)

Future information technologies for low-dissipation quantum computation, high-speed storage, and on-chip communication applications require the development of atomically thin, ultracompact, and ultrafast spintronic devices in which information is encoded, stored, and processed using electron spin. Exploring low-dimensional magnetic materials, designing novel heterostructures, and generating and controlling ultrafast electron spin in 2D magnetism at room temperature, preferably in the unprecedented terahertz (THz) regime, is in high demand. Using THz emission spectroscopy driven by femtosecond laser pulses, optical THz spin-current bursts at room temperature in the 2D van der Waals ferromagnetic Fe 3 GeTe 2 (FGT) integrated with Bi 2 Te 3 as a topological insulator are successfully realized. The symmetry of the THz radiation is effectively controlled by the optical pumping incidence and external magnetic field directions, indicating that the THz generation mechanism is the inverse Edelstein effect contributed spin-to-charge conversion. Thickness-, temperature-, and structure-dependent nontrivial THz transients reveal that topology-enhanced interlayer exchange coupling increases the FGT Curie temperature to room temperature, which provides an effective approach for engineering THz spin-current pulses. These results contribute to the goal of all-optical generation, manipulation, and detection of ultrafast THz spin currents in room-temperature 2D magnetism, accelerating the development of atomically thin high-speed spintronic devices., (© 2022 Wiley-VCH GmbH.)

We conceive and construct an on-site in situ high-pressure time-resolved ultrafast optical spectroscopy instrument that facilitates ultrafast pump-probe dynamics measurements under high pressure conditions. We integrate an ultrafast pump-probe spectroscopy system with a diamond anvil cell (DAC) system. Significantly, both the DAC and the sample are fixed within the light path without motion and rotation throughout the whole ultrafast spectroscopy experiment, including tuning and calibrating the pressure. This instrument thus avoids introducing artifacts due to sample motion or rotation, enabling precision high-pressure ultrafast pump-probe dynamics investigations. As a demonstrating example, we compare the effect of on-site in situ conditions with off-site in situ conditions on the ultrafast dynamics of Sr 2 IrO 4 under 0-44.5 GPa high pressure. Our data and analysis show that conventional possible artifacts are greatly reduced by using the on-site in situ layout. Our work helps the high-pressure ultrafast science investigation develop into a promising new area, which enables the exploration of nonequilibrium excited quantum states in the high-pressure regime.

Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two major types of esophageal cancer (EC). ESCC accounts for 90% of EC. Recurrence after primary treatment is the main reason for poor survival. Therefore, recurrence prevention is a promising strategy for extending the 5-year survival rate. Here, we found tegaserod maleate could inhibit ESCC proliferation both in vivo and in vitro . Proteomics analysis revealed that tegaserod maleate suppressed the peroxisome signaling pathway, in which the key molecules peroxisome membrane protein 11B (PEX11B) and peroxisome membrane protein 13 (PEX13) were downregulated. The immunofluorescence, catalase activity assay, and reactive oxygen species (ROS) confirmed that downregulation of these proteins was related to impaired peroxisome function. Furthermore, we found that PEX11B and PEX13 were highly expressed in ESCC, and knockout of PEX11B and PEX13 further demonstrated the antitumor effect of tegaserod maleate. Importantly, tegaserod maleate repressed ESCC tumor growth in a patient-derived xenograft (PDX) model in vivo . Our findings conclusively demonstrated that tegaserod maleate inhibits the proliferation of ESCC by suppressing the peroxisome pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wu, Wang, Jiang, Zhou, Li, Wei, Bao, Wang, Zhao, Chen, Guo, Dong and Liu.)

Esophageal mucosa undergoes mild, moderate, severe dysplasia, and other precancerous lesions and eventually develops into carcinoma in situ, and understanding the developmental progress of esophageal precancerous lesions is beneficial to prevent them from developing into cancer. DNA polymerase β (Polβ), a crucial enzyme of the base excision repair system, plays an important role in repairing damaged DNA and maintaining genomic stability. Abnormal expression or deletion mutation of Polβ is related to the occurrence of esophageal cancer, but the role of Polβ deficiency in the esophageal precancerous lesions is still unclear. Here, esophageal mucosa Polβ-knockout mice were used to explore the relationship of Polβ deficiency with esophageal precancerous lesions. First, we found the degree and number of esophageal precancerous lesions in Polβ-KO mice were more serious than those in Polβ-Loxp mice after N-nitrosomethylbenzylamine (NMBA) treatment. Whole exome sequencing revealed that deletion of Polβ increased the frequency of gene mutations. Gene expression prolife analysis showed that the expression of proteins correlated to cell proliferation and the cell cycle was elevated in Polβ-KO mice. We also found that deletion of Polβ promoted the proliferation and clone formation as well as accelerated cell cycle progression of human immortalized esophageal epithelial cell line SHEE treated with NMBA. Our findings indicate that Polβ knockout promotes the occurrence of esophageal precancerous lesions., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Esophageal cancer is the ninth most common cancer and the sixth most common cause of cancer-related death worldwide, and the esophageal squamous cell carcinoma (ESCC) subtype accounts for about 90% of all cases of esophageal cancer globally. Currently, ESCC is usually diagnosed in late stages, and targeted therapy is lacking. Therefore, the development of ESCC-specific recognition molecules for an early detection and targeted treatment of ESCC is urgently needed. Aptamers are an excellent molecular recognition tool with unique advantages. In this manuscript, three aptamers (S2, S3, and S8) specific to ESCC cells were successfully screened via cell-SELEX. The experimental results displayed the high affinities of the three aptamers for target KYSE150 cells with dissociation constants in the nanomolar range. The specificity evaluation showed that S2 only bound target KYSE150 cells, but S3 and S8 were capable of targeting a series of ESCC cells. Moreover, several truncated aptamers were generated through sequence optimization. In particular, an ultrashort aptamer S3-2-3 with only 18 bases was successfully obtained; after labeling with Cy5 dyes, it was feasible for the specific imaging of ESCC tissues. Furthermore, the target types of the selected aptamers were preliminarily identified as membrane proteins, and target proteins could be captured by S3-2-3, which may be useful for biomarker discovery. Therefore, the selected aptamers hold great potential for clinical diagnosis, biomarker discovery, and the targeted therapy of ESCC.

Esophageal squamous cell carcinoma (ESCC) is a major type of esophageal cancer. The prognosis of patients with ESCC remains poor because of the high morbidity and mortality of the disease. One strategy for drug discovery for ESCC treatment or prevention is screening FDA-approved drugs. In the present study, we found that the antitussive agent cloperastine can inhibit the proliferation of ESCC cells. However, the underlying mechanism was unclear. To determine the mechanism of this inhibitory effect, we performed proteomic analysis using KYSE150 cells treated with cloperastine and DMSO. The results identified several down-regulated signaling pathways included those of three key proteins (NADH dehydrogenase [ubiquinone] 1 alpha subcomplex 1, NADH ubiquinone oxidoreductase subunit S5, and cytochrome C oxidase subunit 6B1) involved in oxidative phosphorylation. Meanwhile, we observed that oxidative phosphorylation in mitochondria was inhibited by the drug. Importantly, cloperastine suppressed ESCC growth in a xenograft mouse model in vivo. Our findings revealed that cloperastine inhibits the proliferation of ESCC in vivo and in vitro by suppressing mitochondrial oxidative phosphorylation.

Circulating exosomes delivering microRNAs are involved in the occurrence and development of cardiovascular diseases. How are the circulating exosomes involved in the repair of endothelial injury in acute myocardial infarction (AMI) convalescence (3-7 days) was still not clear. In this study, circulating exosomes from AMI patients (AMI-Exo) and healthy controls (Normal-Exo) were extracted. In vitro and in vivo, our study showed that circulating exosomes protected endothelial cells (HUVECs) from oxidative stress damage; meanwhile, Normal-Exo showed better protective effects. Through the application of related inhibitors, we found that circulating exosomes shuttled between HUVECs via dynamin. Microarry analysis and qRT-PCR of circulating exosomes showed higher expression of miR-193a-5p in Normal-Exo. Our study showed that miR-193a-5p was the key factor on protecting endothelial cells in vitro and in vivo. Bioinformatics analyses found that activin A receptor type I (ACVR1) was the potential downstream target of miR-193a-5p, which was confirmed by ACVR1 expression and dual-luciferase report. Inhibitor of ACVR1 showed similar protective effects as miR-193a-5p. While overexpression of ACVR1 could attenuate protective effects of miR-193a-5p. To sum up, these findings suggest that circulating exosomes could shuttle between cells through dynamin and deliver miR-193a-5p to protect endothelial cells from oxidative stress damage via ACVR1., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Aim : This research investigated the therapeutic effect of an allogeneic mouse brain microvascular endothelial cell vaccine on lung cancer and further elucidated its potential anti-angiogenic mechanism. Materials & methods : The immune effect of the allogeneic bEnd.3 vaccine and DC vaccine loaded with bEnd.3 antigen on the subcutaneous transplantation of Lewis lung cancer (LLC) was assessed by ELISA, the CCK test and the CTL killing test. The mechanism was preliminarily revealed by immunohistochemistry and immunoblot analysis. Results : This study revealed that tumor volume was decreased ( p < .01) and the survival was prolonged significantly ( p < .05) by the bEnd.3 vaccine in subcutaneous LLC transplantation in the vaccine prevention group. In contrast, both tumor volume in the serum therapeutic group and survival of bEnd.3 vaccine were not significantly different from those of the control group ( p > .05). Importantly, tumor volume and survival of the T lymphocyte therapeutic group were decreased and prolonged ( p < .05). In addition, both tumor volume and survival of DC vaccine loaded with bEnd.3 in the vaccine prevention group were decreased and prolonged significantly ( p < .01). Furthermore, bEnd.3 vaccine and DC vaccine loaded with bEnd.3 both produced the activity of killing bEnd.3 target cells in vitro.The reason may induce the immune mice to produce anti-VEGFR-II, anti-endoglin and anti-integrin αν antibodies to have an anti-angiogenesis function. Conclusion : The allogeneic mouse bEnd.3 cell vaccine can block angiogenesis and prevent the development of lung cancer transplantation tumors.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors of the digestive tract in humans. Several studies have indicated that PAK4 is associated with the risk of ESCC and may be a potential druggable kinase for ESCC treatment. However, the underlying mechanism remains largely unknown. The aim of our study is to identify the functional role of PAK4 in ESCC. To determine the expression of PAK4 in ESCC, Western blot analysis and immunohistochemistry were performed, and the results showed that PAK4 is significantly upregulated in ESCC tissues and cell lines compared with normal controls and normal esophageal epithelial cell line. To further investigate the role of PAK4 in ESCC, cell viability assays, anchorage-independent cell growth assays, wound healing assays, cellular invasion assays, in vivo xenograft mouse models, and metastasis assays were conducted, and the results showed that PAK4 can significantly facilitate ESCC proliferation and metastasis in vitro and in vivo. To determine the potential target of PAK4 in ESCC progression, a pull-down assay was performed, and the results showed that LASP1 may be a potential target of PAK4. An immunoprecipitation assay and confocal microscopy analysis confirmed that PAK4 can bind to and colocalize with LASP1 in vitro and in cells. Notably, rescue experiments further illustrated the mechanistic network of PAK4/LASP1. Our research reveals the oncogenic roles of PAK4 in ESCC and preliminarily elucidates the mechanistic network of PAK4/LASP1 in ESCC., (© 2020 The Authors. Molecular Carcinogenesis published by Wiley Periodicals LLC.)

Dihydroartemisinin (DHA), a sesquiterpene lactone with endoperoxide bridge, is one of the derivatives of artemisinin. In addition to having good antimalarial properties, DHA exhibits anticancer effects including against malignant solid tumors. However, the mechanism by which DHA inhibits the progression of esophageal cancer, especially esophageal squamous cell carcinoma (ESCC), is unclear. In this study, DHA was found to inhibit the proliferation of ESCC, and the underlying molecular mechanisms were explored. DHA inhibited ESCC cells proliferation and anchorage-independent growth. Flow cytometry analysis revealed that DHA significantly blocked cell cycle in the G1 phase. The results of human phospho-kinase array revealed that DHA downregulated the levels of p70S6K T389 and p70S6K T421/S424 . Furthermore, the levels of mTOR S2448 , p70S6K T389 , p70S6K T421/S424 and RPS6 S235/S236 were decreased after DHA treatment in KYSE30 and KYSE150 cells. We then explored the proteins targeted by DHA to inhibit the mTOR-p70S6K-RPS6 pathway. Results of the in vitro kinase assay revealed that DHA significantly inhibited phosphorylation of mTOR S2448 by binding to AKT1 and p70S6K kinases. In vivo , DHA inhibited the tumor growth of ESCC patient-derived xenografts and weakened p-mTOR, p-p70S6K, and p-RPS6 expression in tumor tissues. Altogether, our results indicate that DHA has antiproliferative effects in ESCC cells and can downregulate mTOR cascade pathway partially by binding to AKT1 and p70S6K. Thus, DHA has considerable potential for the prevention or treatment of ESCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Zhu, Chen, Zhu, Qin, Niu, Ding, Xiao, Jiang, Liu, Lu, Yang, Qiao, Jin, Ma, Dong and Zhao.)

High recurrence rates and poor survival of patients with esophageal squamous cell carcinoma (ESCC) after treatment make ongoing research on chemoprevention drugs for ESCC particularly important. In this study, we screened a large number of FDA-approved drugs and found levodopa, a drug used to treat Parkinson's disease, had an inhibitory effect on the growth of ESCC cells. To elucidate the molecular mechanisms involved, we applied quantitative proteomics to investigate the anti-tumor activity of levodopa on ESCC. The results suggest that levodopa could down-regulate oxidative phosphorylation, non-alcoholic fatty liver disease, and Parkinson's disease pathways. Major mitochondrial respiratory compounds were involved in the pathways, including succinate dehydrogenase subunit D, NADH-ubiquinone oxidoreductase Fe-S protein 4, and mitochondrial cytochrome c oxidase subunit 3. Down-regulation of these proteins was associated with mitochondrial dysfunction. Western blotting and immunofluorescence results confirmed the proteomics findings. Cell viability assays indicated mitochondrial activity was suppressed after levodopa treatment. Reduced mitochondrial membrane potential was detected using JC-1 staining and TMRE assays. Transmission electron microscopy revealed changes in the morphology of mitochondria. Taken together, these results indicate that levodopa inhibited the growth of ESCC through restraining mitochondria function., (Copyright © 2020 Li, Li, He, Jia, Zhang, Lu, Zhao, Lu, Chen, Dong, Liu and Dong.)

Background: Androgenetic alopecia (AGA) represents the most frequent clinical complaint encountered by dermatologists and is characterized by a progressive miniaturization of the hair follicle. However, the efficacy and safety of current medical treatment remain limited, and more personalized therapeutic approaches for AGA are needed. Therefore, the present study is aimed at investigating the efficacy and safety of botulinum toxin type A (BTA) in patients with AGA., Methods: 63 patients with AGA meeting the inclusion criteria were included in this study and treated with BTA injection or BTA injection combined with oral finasteride (FNS). In the scalp, 30 sites were injected with 100 U of BTA in each site and patients received BTA after every 3 months for a total of 4 times. Hair counts, head photographs, evaluation scores, and self-assessment were assessed in patients with AGA., Results: Hair counts in both groups at all time points were significantly higher as compared with those before treatment. After 4 times of treatment, hair counts in the BTA+FNS group were higher than those in the BTA group. Hair growth and density were significantly augmented, and the area of hair loss was attenuated after each treatment as revealed by head photographs. The effective rates of BTA and BTA+FNS groups were 73.3% and 84.8%, respectively, following 4 times treatment., Conclusion: BTA is a safe and effective therapeutic strategy for the treatment of AGA without adverse effects, and BTA combined with FNS exhibited a superior therapeutic effect than BTA alone., Competing Interests: The authors declare that they have no conflicts of interest to disclose., (Copyright © 2020 Yaguang Zhou et al.)

Esophageal squamous cell carcinoma (ESCC) has a worldwide impact on human health, due to its high incidence and mortality. Therefore, identifying compounds to increase patients' survival rate is urgently needed. Mefloquine (MQ) is an FDA-approved anti-malarial drug, which has been reported to inhibit cellular proliferation in several cancers. However, the anti-tumor activities of the drug have not yet been completely defined. In this study, mass spectrometry was employed to profile proteome changes in ESCC cells after MQ treatment. Sub-cellular localization and gene ontology term enrichment analysis suggested that MQ treatment mainly affect mitochondria. The KEGG pathway enrichment map of down-regulated pathways and Venn diagram indicated that all of the top five down regulated signaling pathways contain four key mitochondrial proteins (succinate dehydrogenase complex subunit C (SDHC), succinate dehydrogenase complex subunit D, mitochondrially encoded cytochrome c oxidase III and NADH: ubiquinone oxidoreductase subunit V3). Meanwhile, mitochondrial autophagy was observed in MQ-treated KYSE150 cells. More importantly, patient-derived xenograft mouse models of ESCC with SDHC high expression were more sensitive to MQ treatment than low SDHC-expressing xenografts. Taken together, mefloquine inhibits ESCC tumor growth by inducing mitochondrial autophagy and SDHC plays a vital role in MQ-induced anti-tumor effect on ESCC., (Copyright © 2020 Xie, Zhang, Lu, Bao, Zhao, Lu, Wei, Yao, Jiang, Yuan, Zhang, Li, Chen, Dong and Liu.)

We use an ultrafast optical pump-probe spectroscopy to study quasiparticle (QP) dynamics in a topological insulator LaBi. Temperature-dependent optical measurements have been carried out, by which we observed nearly constant fast component (with a lifetime of 0.15 ps) and slow component (with a lifetime of 1.5 ps) for the whole range from 10 K to 295 K. The laser fluence dependence result shows that there is no saturation for the QP dynamics up to 3.3 mJ /cm 2 . Moreover, an Eg mode transverse optical (TO) coherent phonon has also been observed, with a frequency of 2.8 THz. Our results provide for the first time the ultrafast dynamics information of both the QPs and coherent phonons in a nodal line topological material.

Highly sensitive and specific detection of rare tumor cells is urgently needed for early tumor diagnosis. Herein, a split aptamer-based dual hybridization chain reaction (dual-HCR) strategy with flow cytometry analysis was developed to meet this purpose. With the split aptamer pair as the recognition unit and HCR as the signal amplification technique, this strategy achieved an improved detection limit as low as 20 cells in 200 μL binding buffer. Meanwhile, this method was highly specific with distinct recognition of the target cells from the control cell and mixed cell samples. Furthermore, we succeeded in the specific detection of the target cells in 50% human serum, demonstrating that this method has great potential in clinical applications. In theory, this strategy can be used to detect different target cells by using different split aptamers. Therefore, this general, sensitive and specific tumor cell detection method may be helpful for early clinical diagnosis and cancer research.

The high incidence and mortality of esophageal squamous cell cancer (ESCC) is a major health problem worldwide. Precancerous lesions of ESCC may either progress to cancer or revert to normal epithelium with appropriate interventions; the bidirectional instability of the precancerous lesions of ESCC provides opportunities for intervention. Reports suggest that the upregulation of ornithine decarboxylase (ODC) is closely related to carcinogenesis. In this study, we investigated whether ODC may act as a target for chemoprevention in ESCC. Immunohistochemistry (IHC) assays indicate that ODC expression is higher in esophageal precancerous lesions compared with normal tissue controls. Its overexpression promotes cell proliferation and transformation of normal esophageal epithelial cells, and its activity is increased after N-nitrosomethylbenzylamine (NMBA) induction in Shantou human embryonic esophageal cell line (SHEE) and human immortalized cells (Het1A) cells. In addition, p38 α, extracellular regulated kinase (ERK1/2) in the mitogen-activated protein kinase pathway and protein kinase B (AKT)/mammalian target of rapamycin (mTOR)/ribosomal protein S6 kinase (p70S6K) pathways are activated in response to NMBA treatment. Difluoromethylornithine (DFMO) is an ODC inhibitor, which inhibits NMBA-induced activation of p38 α, ERK1/2 and AKT/mTOR/p70S6K pathways; this has been verified by Western blotting. DFMO was also found to suppress the development of esophageal precancerous lesions in an NMBA-induced rat model; IHC demonstrated p38 α, ERK1/2, and AKT/mTOR/p70S6K pathways to be downregulated in these rats. These findings indicate the mechanisms by which ODC inhibition suppresses the development of esophageal precancerous lesions by downregulating p38 α, ERK1/2, and AKT/mTOR/p70S6k signaling pathways, ODC may be a potential target for chemoprevention in ESCC., (© 2019 Wiley Periodicals, Inc.)

Understanding the molecular mechanisms of precancerous lesion of esophageal cancer is beneficial for early diagnosis and early treatment. The deletion of p53 gene is common in esophageal cancer, but its pathogenesis is still unclear. An animal model is urgently needed to study the mechanisms of esophageal cancer and p53 deficiency. KO mice (p53 flox/flox .ED-L2-Cre +/- ) and the corresponding control Loxp mice (p53 flox/flox .ED-L2-Cre -/- ) were obtained by crossing between the p53 flox/flox mice and ED-L2-Cre +/- mice. Methylbenzylnitrosamine (NMBA) was injected subcutaneously to induce esophageal precancerous lesion of these two groups of mice. Hematoxylin and eosin staining analysis was performed to evaluate the number and extent of esophageal precancerous lesions in KO mice and Loxp mice at the 16th and 48th weeks. Immunohistochemistry analysis was used to detect the change of Ki67, P21, Bcl-2, and Bax proteins. The number and extent of esophageal precancerous lesions in KO mice were significantly increased compared with the control at the 16th and 48th weeks under the induction of NMBA. The Ki67, P21, Bcl-2, and Bax proteins also had cancer-related pathological characteristics. These results suggest that the esophageal precancerous lesion model was established under the combined effect of p53 gene deletion in esophageal epithelium and NMBA, which could provide a new esophageal precancerous lesion model to explore the mechanism of precancerous lesions., Competing Interests: The authors have no conflicts of interest., (Copyright © 2020 Lili Zhu et al.)

Following publication of the original article [1], the authors reported the errors in Fig. 1C and D, Fig. 2, Fig. 4B and C and Fig. 6D and E.