Spatiotemporal genotype replacement of H5N8 avian influenza viruses contributed to H5N1 emergence in 2021/2022 panzootic.

Since 2020, clade 2.3.4.4b highly pathogenic avian influenza H5N8 and H5N1 viruses have swept through continents, posing serious threats to the world. Through comprehensive analyses of epidemiological, genetic, and bird migration data, we found that the dominant genotype replacement of the H5N8 viruses in 2020 contributed to the H5N1 outbreak in the 2021/2022 wave. The 2020 outbreak of the H5N8 G1 genotype instead of the G0 genotype produced reassortment opportunities and led to the emergence of a new H5N1 virus with G1's HA and MP genes. Despite extensive reassortments in the 2021/2022 wave, the H5N1 virus retained the HA and MP genes, causing a significant outbreak in Europe and North America. Furtherly, through the wild bird migration flyways investigation, we found that the temporal-spatial coincidence between the outbreak of the H5N8 G1 virus and the bird autumn migration may have expanded the H5 viral spread, which may be one of the main drivers of the emergence of the 2020-2022 H5 panzootic.IMPORTANCESince 2020, highly pathogenic avian influenza (HPAI) H5 subtype variants of clade 2.3.4.4b have spread across continents, posing unprecedented threats globally. However, the factors promoting the genesis and spread of H5 HPAI viruses remain unclear. Here, we found that the spatiotemporal genotype replacement of H5N8 HPAI viruses contributed to the emergence of the H5N1 variant that caused the 2021/2022 panzootic, and the viral evolution in poultry of Egypt and surrounding area and autumn bird migration from the Russia-Kazakhstan region to Europe are important drivers of the emergence of the 2020-2022 H5 panzootic. These findings provide important targets for early warning and could help control the current and future HPAI epidemics.

ß-catenin promotes resistance to trastuzumab in breast cancer cells through enhancing interaction between HER2 and SRC.

More than 1 million women worldwide are diagnosed with breast cancer (BC) each year. This study aims to explore the molecular mechanisms of ß-catenin affecting the trastuzumab tolerance in HER2-positive BC. ß-catenin in BC and non-BC tissue samples were assessed by immunohistochemistry. ß-catenin and HER2 were over-expressed and knockdown to evaluate their role in tumorigenicity and trastuzumab resistance in cell and animal models using soft-agar and xenograft assays. Confocal laser immunofluorescence assay and co-immunoprecipitation were used to assess protein-protein binding. Expression of genes was detected using Western blot analysis. ß-catenin was highly expressed in primary and metastatic BC, overexpression of ß-catenin increased the colony formation of MCF7 cells when it was co-expressed with HER2 and synergically increased the tumor size in immunodeficient mice. Overexpression of ß-catenin also increased the phosphorylation of HER2 and HER3 and increased the size of tumor derived from HER2-elevated cells. Confocal laser immunofluorescence assay showed that ß-catenin and HER2 were co-localized on the membrane of MDA-MB-231 cells, suggesting that ß-catenin binds HER2 to activate the HER2 signaling pathway. Immunoprecipitation of ß-catenin and HER2 also confirmed this binding. On the other hand, knockdown of ß-catenin in MDA-MB-231 cell lines decreased the activity of SRC and decreased phosphorylation of HER2 at Y877 and Y1248. The interaction between HER2 and SRC was enhanced when ß-catenin was overexpressed, and ß-catenin increased the resistance of tumor derived from HER2 elevated BT474 cells to trastuzumab. Further analysis showed that trastuzumab inhibited the activation of HER3, but SRC was still highly expressed in cells overexpressing ß-catenin. Our work demonstrates that ß-catenin is highly expressed in BC and it synergically promotes formation and progress of BC with HER2. ß-catenin binds with HER2 leading to enhanced interaction with SRC and resistance to trastuzumab.

Variation in synonymous evolutionary rates in the SARS-CoV-2 genome.

Introduction: Coronavirus disease 2019 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Influential variants and mutants of this virus continue to emerge, and more effective virus-related information is urgently required for identifying and predicting new mutants. According to earlier reports, synonymous substitutions were considered phenotypically silent; thus, such mutations were frequently ignored in studies of viral mutations because they did not directly cause amino acid changes. However, recent studies have shown that synonymous substitutions are not completely silent, and their patterns and potential functional correlations should thus be delineated for better control of the pandemic. Methods: In this study, we estimated the synonymous evolutionary rate (SER) across the SARS-CoV-2 genome and used it to infer the relationship between the viral RNA and host protein. We also assessed the patterns of characteristic mutations found in different viral lineages. Results: We found that the SER varies across the genome and that the variation is primarily influenced by codon-related factors. Moreover, the conserved motifs identified based on the SER were found to be related to host RNA transport and regulation. Importantly, the majority of the existing fixed-characteristic mutations for five important virus lineages (Alpha, Beta, Gamma, Delta, and Omicron) were significantly enriched in partially constrained regions. Discussion: Taken together, our results provide unique information on the evolutionary and functional dynamics of SARS-CoV-2 based on synonymous mutations and offer potentially useful information for better control of the SARS-CoV-2 pandemic.

Knockdown of NCAPG promotes the apoptosis and inhibits the invasion and migration of triple­negative breast cancer MDA­MB­231 cells via regulation of EGFR/JAK/STAT3 signaling.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and the treatment options are extremely limited. Non-SMC condensing I complex subunit G (NCAPG) expression is upregulated in TNBC, but its specific regulatory mechanism in TNBC has not been previously reported. The expression levels of NCAPG in TNBC were analyzed using data obtained from the UALCAN database. RT-qPCR and western blotting were used to detect the expression of NCAPG in various breast cancer cell lines. The expression of NCAPG was knocked down, and cell viability was then detected using a CCK-8 assay, apoptosis was detected using a TUNEL assay, and the expression of the apoptosis-related proteins Bcl-2, Bax and Bad were detected by western blotting. Wound healing and Transwell assays were used to assess migration and invasion. Western blotting was also used to determine the expression levels of migration and invasion-related proteins MMP2 and MMP9, as well as EGFR/JAK/STAT3 pathway-related proteins. Following exogenous treatment with EGF and the JAK/STAT3 signaling pathway agonist colivelin, cell viability, apoptosis, invasion and migration were assessed. The expression of NCAPG in TNBC MDA-MB-231 cells was significantly increased. Inhibition of NCAPG inhibited the activity, promoted apoptosis, and inhibited the invasion and migration of TNBC MDA-MB-231 cells, potentially via regulation of the EGFR/JAK/STAT3 signaling pathway. In conclusion, downregulation of NCAPG can promote apoptosis and inhibit invasion and migration of TNBC MDA-MB-231 cells via EGFR/JAK/STAT3 signaling.

The diversity and evolution of retroviruses: Perspectives from viral "fossils".

Retroviruses exclusively infect vertebrates, causing a variety of diseases. The replication of retroviruses requires reverse transcription and integration into host genomes. When infecting germline cells, retroviruses become inherited vertically, forming endogenous retroviruses (ERVs). ERVs document past viral infections, providing molecular fossils for studying the evolutionary history of retroviruses. In this review, we summarize the recent advances in understanding the diversity and evolution of retroviruses from the perspectives of viral fossils, and discuss the effects of ERVs on the evolution of host biology.

Molecular fossils illuminate the evolution of retroviruses following a macroevolutionary transition from land to water.

The ancestor of cetaceans underwent a macroevolutionary transition from land to water early in the Eocene Period >50 million years ago. However, little is known about how diverse retroviruses evolved during this shift from terrestrial to aquatic environments. Did retroviruses transition into water accompanying their hosts? Did retroviruses infect cetaceans through cross-species transmission after cetaceans invaded the aquatic environments? Endogenous retroviruses (ERVs) provide important molecular fossils for tracing the evolution of retroviruses during this macroevolutionary transition. Here, we use a phylogenomic approach to study the origin and evolution of ERVs in cetaceans. We identify a total of 8,724 ERVs within the genomes of 25 cetaceans, and phylogenetic analyses suggest these ERVs cluster into 315 independent lineages, each of which represents one or more independent endogenization events. We find that cetacean ERVs originated through two possible routes. 298 ERV lineages may derive from retrovirus endogenization that occurred before or during the transition from land to water of cetaceans, and most of these cetacean ERVs were reaching evolutionary dead-ends. 17 ERV lineages are likely to arise from independent retrovirus endogenization events that occurred after the split of mysticetes and odontocetes, indicating that diverse retroviruses infected cetaceans through cross-species transmission from non-cetacean mammals after the transition to aquatic life of cetaceans. Both integration time and synteny analyses support the recent or ongoing activity of multiple retroviral lineages in cetaceans, some of which proliferated into hundreds of copies within the host genomes. Although ERVs only recorded a proportion of past retroviral infections, our findings illuminate the complex evolution of retroviruses during one of the most marked macroevolutionary transitions in vertebrate history.

Ursolic acid induces apoptosis and anoikis in colorectal carcinoma RKO cells.

BACKGROUND: Ursolic acid (UA) is an anti-cancer herbal compound. In the present study, we observed the effects of UA on anchorage-dependent and -independent growth of human colorectal cancer (CRC) RKO cells. METHODS: RKO cells were cultured in conventional and detached condition and treated with UA. Cell viability was evaluated by CCK-8 assay. Cell cycle was analyzed by flow cytometry. Apoptosis was identified by Hoechst 33258 staining and flow cytometry analysis. Activities of caspases were measured by commercial kits. Reactive oxygen species (ROS) was recognized by DCFH-DA fluorescent staining. Anoikis was identified by EthD-1 fluorescent staining and flow cytometry analysis. Expression and phosphorylation of proteins were analyzed by western blot. RESULTS: UA inhibited RKO cell viability in both a dose- and time-dependent manner. UA arrested the cell cycle at the G0/G1 phase, and induced caspase-dependent apoptosis. UA inhibited Bcl-2 expression and increased Bax expression. In addition, UA up-regulated the level of ROS that contributed to UA activated caspase-3, - 8 and - 9, and induced apoptosis. Furthermore, UA inhibited cell growth in a detached condition and induced anoikis in RKO cells that was accompanied by dampened phosphorylation of FAK, PI3K and AKT. UA also inhibited epithelial-mesenchymal transition (EMT) as indicated by the down-regulation of N-Cad expression and up-regulation of E-Cad expression. CONCLUSIONS: UA induced caspase-dependent apoptosis, and FAK/PI3K/AKT singling and EMT related anoikis in RKO cells. UA was an effective anti-cancer compound against both anchorage-dependent and -independent growth of RKO cells.

Flexible photodetectors based on reticulated SWNT/perovskite quantum dot heterostructures with ultrahigh durability.

Recently, single-walled carbon nanotube (SWNT) films have been regarded as a promising channel material for flexible photodetectors due to their high intrinsic carrier mobility, conductivity, and mechanical flexibility. However, the application of SWNTs in photonic devices is limited due to their weak light absorption and the absence of a gain mechanism. Here, we demonstrate a high-performance flexible photodetector that consists of a reticulated SWNT film covered with a thin film of CsPbI3 perovskite colloidal quantum dots. The unique hierarchical reticulated structure of the SWNTs provides such films with extremely high tensile strength and great extensibility, which can ensure the appropriate toughness for achieving flexible photodetectors. Meanwhile, the perovskite quantum dots enhance light absorption, thereby sensitizing the creation of free electrical carriers within the SWNTs. This hybrid photodetector exhibits an extended photonic response and gain compared with the original pure SWNT devices. In addition, the device exhibits good robustness against repetitive bending and stretching, suggesting its applicability as a large-area wearable flexible photodetector.

Traditional Chinese medicine formulation Yanggan Jiedu Sanjie inhibits TGF-ß1-induced epithelial-mesenchymal transition and metastatic potential in human hepatocarcinoma Bel-7402 cells.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is a vital process in cancer progression and metastasis. Yanggan Jiedu Sanjie (YGJDSJ) is Traditional Chinese Medicine formulation for liver cancer treatment. In the present study, we evaluated the effects of YGJDSJ on TGF-ß1-induced EMT in hepatocellular carcinoma Bel-7402 cells. METHODS: Bel-7402 cells were treated with TGF-ß1 and YGJDSJ. EMT was identified by morphological changes and expression of marker proteins. Cell morphology was observed under a microscope. Protein expression and phosphorylation was detected by western blotting. Cell migration was measured by the scratch assay. Cell adhesion and invasion was detected by a commercial kit. RESULTS: YGJDSJ reversed TGF-ß1-induced morphological changes, as well as the expression of the EMT markers E-cadherin and N-cadherin in Bel-7402 cells. YGJDSJ also inhibited TGF-ß1 up-regulated Smad3 phosphorylation and Snail expression in Bel-7402 cells. Moreover, YGJDSJ inhibited TGF-ß1-induced cell adhesion, migration and invasion in Bel-7402 cells. CONCLUSIONS: YGJDSJ inhibited TGF-ß1-induced EMT and mediated metastatic potential of Bel-7402 cells, which may be related to down-regulation of Smad3 phosphorylation and Snail expression. The present study provides a new basis for application of this herbal formula for prevention of liver cancer metastasis.

Effect of Yanggan Jiedu Sanjie formula on human hepatocellular carcinoma Bel-7402 cells.

OBJECTIVE: To observe the effect of Yanggan Jiedu Sanjie (YGJDSJ) formula on human hepatocellular carcinoma Bel-7402 cells. METHODS: Bel-7402 cells were treated with YGJDSJ. Cell proliferation was detected by cell counting kit-8 assay. Cell apoptosis was identified by Hoechst 33258 staining and flow cytometric analysis. Cell cycle distribution was quantified by flow cytometric analysis. Caspase activities were measured by commercial kit. Cell senescence was detected by senescence-associated ß-galactosidase (SA-ß-gal) staining. Protein expression and phosphorylation were identified by Western blot. Protein expression was knocked-down by siRNA. RESULTS: YGJDSJ inhibited proliferation of Bel- 7402 cells in a dose- and time-dependent manner. YGJDSJ induced apoptosis and activated caspase- 3, 8, and 9 in Bel-7402 cells. YGJDSJ-induced apoptosis was completely abrogated by a pan caspase inhibitor, Z-VAD-FMK. YGJDSJ also induced cell senescence, up-regulated cyclin-dependent kinase inhibitor 1a (CDKN1a) and CDKN2a expression and down-regulated retinoblastoma protein (RB) phosphorylation in Bel-7402 cells. Specific knockdown of CDKN1a and CDKN2a significantly reduced YGJDSJ-induce cell senescence in Bel-7402 cells. CONCLUSION: YGJDSJ inhibited cell proliferation, induced caspase-dependent apoptosis and CDKN1a/CDKN2a-RB signalling mediated cell senescence in Bel-7402 cells. Our findings suggest that YGJDSJ might be potential for hepatocellular carcinoma treatment.

Herbal formula YGJDSJ inhibits anchorage-independent growth and induces anoikis in hepatocellular carcinoma Bel-7402 cells.

BACKGROUND: Based on clinical medications and related studies, we established a Yang-Gan Jie-Du Sang-Jie (YGJDSJ) herbal formula for hepatocarcinoma treatment. In present study, we evaluated the anti-cancer potential of YGJDSJ on suspension-grown human hepatocellular carcinoma Bel-7402 cells. METHODS: Bel-7402 cells were cultured in poly(2-hydroxyethyl methacrylate) (poly-HEMA) coated plates and treated with YGJDSJ. Anchorage-independent cell growth was detected by cell Counting Kit-8 (CCK-8) assay and soft agar colony formation assay. Anoikis was detected by ethdium homodimer-1 (EthD-1) staining and flow cytometry analysis. Caspases activities were detected by the cleavage of chromogenic substrate. Reactive oxygen species (ROS) was detected by 2',7'-dichlorofluorescin diacetate (DCFH-DA) staining. Protein expression and phosphorylation was identified by western blot. Protein expression was knocked-down by siRNA. RESULTS: YGJDSJ inhibited the proliferation of Bel-7402 cells in poly-HEMA coated plates and anchorage-independent growth of Bel-7402 cells in soft agar. YGJDSJ also induced anoikis in Bel-7402 cells as indicated by EthD-1 staining and flow cytometry analysis. YGJDSJ activated caspase-3, - 8, and - 9 in suspension-grown Bel-7402 cells. The pan-caspase inhibitor Z-VAD-FMK significantly abrogated the effects of YGJDSJ on anoikis in suspension-grown Bel-7402 cells. In addition, YGJDSJ increased ROS in suspension-grown Bel-7402 cells. The ROS scavenger N-acetyl-L-cysteine (NAC) partially attenuated YGJDSJ-induced activation of caspase-3, - 8 and - 9 and anoikis in suspension-grown Bel-7402 cells. Furthermore, YGJDSJ inhibited expression and phosphorylation of protein tyrosine kinase 2 (PTK2) in suspension-grown Bel-7402 cells. Over-expression of PTK2 significantly abrogated YGJDSJ induced anoikis. CONCLUSIONS: YGJDSJ inhibits anchorage-independent growth and induce caspase-mediated anoikis in Bel-7402 cells, and may relate to ROS generation and PTK2 downregulation.

Synthesis of Ultrathin Composition Graded Doped Lateral WSe2/WS2 Heterostructures.

Lateral transition-metal dichalcogenide and their heterostructures have attracted substantial attention, but there lacks a simple approach to produce large-scaled optoelectronic devices with graded composition. In particular, the incorporation of substitution and doping into heterostructure formation is rarely reported. Here, we demonstrate growth of a composition graded doped lateral WSe2/WS2 heterostructure by ambient pressure chemical vapor deposition in a single heat cycle. Through Raman and photoluminescence spectroscopy, we demonstrate that the monolayer heterostructure exhibits a clear interface between two domains and a graded composition distribution in each domain. The coexistence of two distinct doping modes, i.e., interstitial and substitutional doping, was verified experimentally. A distinct three-stage growth mechanism consisting of nucleation, epitaxial growth, and substitution was proposed. Electrical transport measurements reveal that this lateral heterostructure has representative characteristics of a photodiodes. The optoelectronic device based on the lateral WSe2/WS2 heterostructure shows improved photodetection performance in terms of a reasonable responsivity and a large photoactive area.

Teng-Long-Bu-Zhong-Tang induces p21-dependent cell senescence in colorectal carcinoma LS174T cells via histone acetylation.

Teng-Long-Bu-Zhong-Tang (TLBZT) is a Chinese herbal formula for colorectal carcinoma treatment. TLBZT effectively induces cell senescence in colorectal carcinoma, accompanied by p21 upregulation. In this study, we further explored the role of p21 in TLBZT-induced cell senescence, as well as the mechanism by which TLBZT upregulates p21. Specific knockdown of p21 expression by small interfering RNA significantly attenuated TLBZT-induced cell senescence in human colorectal carcinoma LS174T cells. Silencing of p53 by small interfering RNA did not affect TLBZT-induced p21 upregulation. Meanwhile, TLBZT inhibited histone deacetylase activity. Furthermore, TLBZT increased acetylation levels of histone H3 and H4, enhancing their binding to the p21 promoter. These data suggested that TLBZT induces cell senescence in LS174T cells through a mechanism involving p21 upregulation via histone H3 and H4 acetylation. This study provides new insights into the application of TLBZT for colorectal carcinoma treatment.

Controlled Growth of Monocrystalline Organo-Lead Halide Perovskite and Its Application in Photonic Devices.

Organo-lead halide perovskites (OHPs) have recently emerged as a new class of exceptional optoelectronic materials, which may find use in many applications, including solar cells, light emitting diodes, and photodetectors. More complex applications, such as lasers and electro-optic modulators, require the use of monocrystalline perovskite materials to reach their ultimate performance levels. Conventional methods for forming single crystals of OHPs like methylammonium lead bromide (MAPbBr3 ) afford limited control over the product morphology, rendering the assembly of defined microcavity nanostructures difficult. We overcame this by synthesizing for the first time (MA)[PbBr3 ]⋅DMF (1), and demonstrating its facile transformation into monocrystalline MAPbBr3 microplatelets. The MAPbBr3 microplatelets were tailored into waveguide based photonic devices, of which an ultra-low propagation loss of 0.04 dB µm-1 for a propagation distance of 100 µm was demonstrated. An efficient active electro-optical modulator (AEOM) consisting of a MAPbBr3 non-linear arc waveguide was demonstrated, exhibiting a 98.4 % PL intensity modulation with an external voltage of 45 V. This novel synthetic approach, as well as the demonstration of effective waveguiding, will pave the way for developing a wide range of photonic devices based on organo-lead halide perovskites.

Herbal compound Teng-Long-Bu-Zhong-Tang inhibits metastasis in human RKO colon carcinoma.

Metastasis is one of the primary obstacles to the successful treatment of colorectal cancer. Teng-Long-Bu-Zhong-Tang (TLBZT) is a modern Chinese herbal formula that may be useful in the treatment of metastatic colorectal cancer. The present study evaluated the effects of TLBZT on lung metastasis in human RKO colon carcinoma cells injected into mice via the tail vein. The results demonstrated that TLBZT inhibited the metastasis of human RKO colon carcinoma cells to the lungs. TLBZT downregulated the expression of LOX and hypoxia-inducible factor 1α. TLBZT also inhibited the expression of integrins αV and ß3 and the phosphorylation of focal adhesion kinase. These results indicate that TLBZT inhibits the lung metastasis of RKO colon carcinoma by regulating the expression of multiple genes. The results of the present study provide a new basis for the management of colorectal cancer metastasis using treatments derived from Chinese herbs.

Synthesis, properties, and optical applications of low-dimensional perovskites.

Metal-halide perovskites have been hailed as remarkable materials for photovoltaic devices and, recently, their star has also been on the rise in optoelectronics and photonics. In particular, the optical properties of a metal-halide perovskite can be widely manipulated once its bulk structure has been reduced to a low-dimensional structure, allowing multiple functionalities of light generation, emission, transmission, and detection to be realized in one material. In this paper, we highlight the recent advances in the synthesis of low-dimensional metal-halide perovskites and their unique properties as well as their novel optoelectronic and photonic applications. It is anticipated that this review can serve as an overview and evaluation of state-of-the-art synthesis techniques as well as nanoscale optoelectronics and photonics based on low-dimensional perovskite nanocrystals.

Reversible Structural Swell-Shrink and Recoverable Optical Properties in Hybrid Inorganic-Organic Perovskite.

Ion migration in hybrid organic-inorganic perovskites has been suggested to be an important factor for many unusual behaviors in perovskite-based optoelectronics, such as current-voltage hysteresis, low-frequency giant dielectric response, and the switchable photovoltaic effect. However, the role played by ion migration in the photoelectric conversion process of perovskites is still unclear. In this work, we provide microscale insights into the influence of ion migration on the microstructure, stability, and light-matter interaction in perovskite micro/nanowires by using spatially resolved optical characterization techniques. We observed that ion migration, especially the migration of MA(+) ions, will induce a reversible structural swell-shrink in perovskites and recoverably affect the reflective index, quantum efficiency, light-harvesting, and photoelectric properties. The maximum ion migration quantity in perovskites was as high as approximately 30%, resulting in lattice swell or shrink of approximately 4.4%. Meanwhile, the evidence shows that ion migration in perovskites could gradually accelerate the aging of perovskites because of lattice distortion in the reversible structural swell-shrink process. Knowledge regarding reversible structural swell-shrink and recoverable optical properties may shed light on the development of optoelectronic and converse piezoelectric devices based on perovskites.

Scalable Production of a Few-Layer MoS2/WS2 Vertical Heterojunction Array and Its Application for Photodetectors.

Vertical heterojunctions of two two-dimensional (2D) transition metal dichalcogenides (TMDs) have attracted considerable attention recently. A variety of heterojunctions can be constructed by stacking different TMDs to form fundamental building blocks in different optoelectronic devices such as photodetectors, solar cells, and light-emitting diodes. However, these applications are significantly hampered by the challenges of large-scale production of van der Waals stacks of atomically thin materials. Here, we demonstrate scalable production of periodic patterns of few-layer WS2, MoS2, and their vertical heterojunction arrays by a thermal reduction sulfurization process. In this method, a two-step chemical vapor deposition approach was developed to effectively prevent the phase mixing of TMDs in an unpredicted manner, thus affording a well-defined interface between WS2 and MoS2 in the vertical dimension. As a result, large-scale, periodic arrays of few-layer WS2, MoS2, and their vertical heterojunctions can be produced with desired size and density. Photodetectors based on the as-produced MoS2/WS2 vertical heterojunction arrays were fabricated, and a high photoresponsivity of 2.3 A·W(-1) at an excitation wavelength of 450 nm was demonstrated. Flexible photodetector devices using MoS2/WS2 heterojunction arrays were also demonstrated with reasonable signal/noise ratio. The approach in this work is also applicable to other TMD materials and can open up the possibilities of producing a variety of vertical van der Waals heterojunctions in a large scale toward optoelectronic applications.