A Novel Tetramethylpyrazine Chalcone Hybrid- HCTMPPK, as a Potential Anti-Lung Cancer Agent by Downregulating MELK.

Purpose: Lung adenocarcinoma currently ranks the leading causes of cancer-related mortality worldwide. Many anti-inflammation herbs, like tetramethylpyrazine, have shown their anti-tumor potentials. Here, we evaluated the role of a novel chalcone derivative of tetramethylpyrazine ((E) -1- (E) -1- (2-hydroxy-5-chlorophenyl) -3- (3,5,6-trimethylpyrazin-2-yl) -2-propen-1, HCTMPPK) in lung adenocarcinoma. Methods: The effects of HCTMPPK on cell proliferation, apoptosis, and invasion were investigated by in-vitro assays, including CCK-8, colony formation assay, flow cytometry, transwell assay, and wound-healing assay. The therapeutic potential of HCTMPPK in vivo was evaluated in xenograft mice. To figure out the target molecules of HCTMPPK, a network pharmacology approach and molecular docking studies were employed, and subsequent experiments were conducted to confirm these candidate molecules. Results: HCTMPPK effectively suppressed the proliferative activity and migration, as well as enhanced the apoptosis of A549 cells in a concentration-dependent manner. Consistent with this, tumor growth was inhibited by HCTMPPK significantly in vivo. Regarding the mechanisms, HCTMPPK down-regulated Bcl-2 and MMP-9 and up-regulating Bax and cleaved-caspase-3. Subsequently, we identified 601 overlapping DEGs from LUAD patients in TCGA and GEO database. Then, 15 hub genes were identified by PPI network and CytoHubba. Finally, MELK was verified to be the HCTMPPK targeted site, through the molecular docking studies and validation experiments. Conclusion: Overall, our study indicates HCTMPPK as a potential MELK inhibitor and may be a promising candidate for the therapy of lung cancer.

1T'-transition metal dichalcogenide monolayers stabilized on 4H-Au nanowires for ultrasensitive SERS detection.

Unconventional 1T'-phase transition metal dichalcogenides (TMDs) have aroused tremendous research interest due to their unique phase-dependent physicochemical properties and applications. However, due to the metastable nature of 1T'-TMDs, the controlled synthesis of 1T'-TMD monolayers (MLs) with high phase purity and stability still remains a challenge. Here we report that 4H-Au nanowires (NWs), when used as templates, can induce the quasi-epitaxial growth of high-phase-purity and stable 1T'-TMD MLs, including WS2, WSe2, MoS2 and MoSe2, via a facile and rapid wet-chemical method. The as-synthesized 4H-Au@1T'-TMD core-shell NWs can be used for ultrasensitive surface-enhanced Raman scattering (SERS) detection. For instance, the 4H-Au@1T'-WS2 NWs have achieved attomole-level SERS detections of Rhodamine 6G and a variety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins. This work provides insights into the preparation of high-phase-purity and stable 1T'-TMD MLs on metal substrates or templates, showing great potential in various promising applications.

Abnormal performance of peroral endoscopic myotomy (POEM): a case misdiagnosed as achalasia of cardia.

BACKGROUND: Pseudoachalasia is a rare disease that behaves similarly to achalasia (AC), making it sometimes difficult to differentiate. CASE PRESENTATION: We report a case of 49-year-old male with adenocarcinoma of the gastroesophageal junction misdiagnosed as achalasia. No obvious abnormalities were found in his initial examinations including upper digestive endoscopy, upper gastrointestinal imaging and chest computed tomography (CT). During the subsequent introduced-peroral endoscopic myotomy (POEM), it was found that the mucosal layer and the muscular layer had severe adhesion, which did not receive much attention, delayed the clear diagnosis and effect treatment, and ultimately led to a poor prognosis for the patient. CONCLUSIONS: This case suggests that when patients with AC found mucosal and muscular adhesions during POEM surgery, the possibility should be considered that the lesion may be caused by a malignant lesion.

Phase Engineering of Nanomaterials: Transition Metal Dichalcogenides.

Crystal phase, a critical structural characteristic beyond the morphology, size, dimension, facet, etc., determines the physicochemical properties of nanomaterials. As a group of layered nanomaterials with polymorphs, transition metal dichalcogenides (TMDs) have attracted intensive research attention due to their phase-dependent properties. Therefore, great efforts have been devoted to the phase engineering of TMDs to synthesize TMDs with controlled phases, especially unconventional/metastable phases, for various applications in electronics, optoelectronics, catalysis, biomedicine, energy storage and conversion, and ferroelectrics. Considering the significant progress in the synthesis and applications of TMDs, we believe that a comprehensive review on the phase engineering of TMDs is critical to promote their fundamental studies and practical applications. This Review aims to provide a comprehensive introduction and discussion on the crystal structures, synthetic strategies, and phase-dependent properties and applications of TMDs. Finally, our perspectives on the challenges and opportunities in phase engineering of TMDs will also be discussed.

A WRI1-dependent module is essential for the accumulation of auxin and lipid in somatic embryogenesis of Arabidopsis thaliana.

The potential for totipotency exists in all plant cells; however, the underlying mechanisms remain largely unknown. Earlier findings have revealed that the overexpression of LEAFY COTYLEDON 2 (LEC2) can directly trigger the formation of somatic embryos on the cotyledons of Arabidopsis. Furthermore, cotyledon cells that overexpress LEC2 accumulate significant lipid reserves typically found in seeds. The precise mechanisms and functions governing lipid accumulation in this process remain unexplored. In this study, we demonstrate that WRINKLED1 (WRI1), the key regulator of lipid biosynthesis, is essential for somatic embryo formation, suggesting that WRI1-mediated lipid biosynthesis plays a crucial role in the transition from vegetative to embryonic development. Our findings indicate a direct interaction between WRI1 and LEC2, which enhances the enrichment of LEC2 at downstream target genes and stimulates their induction. Besides, our data suggest that WRI1 forms a complex with LEC1, LEC2, and FUSCA3 (FUS3) to facilitate the accumulation of auxin and lipid for the somatic embryo induction, through strengthening the activation of YUCCA4 (YUC4) and OLEOSIN3 (OLE3) genes. Our results uncover a regulatory module controlled by WRI1, crucial for somatic embryogenesis. These findings provide valuable insights into our understanding of plant cell totipotency.

RALDH1 Inhibition Shows Immunotherapeutic Efficacy in Hepatocellular Carcinoma.

Globally, hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers and a leading cause of cancer-related death. We previously identified an immune evasion pathway whereby tumor cells produce retinoic acid (RA) to promote differentiation of intratumoral monocytes into protumor macrophages. Retinaldehyde dehydrogenase 1 (RALDH1), RALDH2, and RALDH3 are the three isozymes that catalyze RA biosynthesis. In this study, we have identified RALDH1 as the key driver of RA production in HCC and demonstrated the efficacy of RALDH1-selective inhibitors (Raldh1-INH) in suppressing RA production by HCC cells. Raldh1-INH restrained tumor growth in multiple mouse models of HCC by reducing the number and tumor-supporting functions of intratumoral macrophages as well as increasing T-cell infiltration and activation within tumors. Raldh1-INH also displayed favorable pharmacokinetic, pharmacodynamic, and toxicity profiles in mice thereby establishing them as promising new drug candidates for HCC immunotherapy.

Right atrial wall inflammation detected by 18F-FDG PET/CT may be significantly associated with persistent atrial fibrillation: a prospective case-control study.

AIM: Atrial fibrillation (AF) is a progressive disease from paroxysmal to persistent, and persistent AF (PerAF) had worse prognosis. AF has potential link with inflammation, but it is not clear whether PerAF or paroxysmal AF (ParAF) is more closely related to inflammation. On the basis of inhibiting myocardial physiological uptake, 18F-fluorodeoxyglucosepositron emission tomography/computed tomography (18F-FDG PET/CT) is an established imaging modality to detect cardiac inflammation. We aimed to decipher the association between AF and atrial inflammatory activity by 18F-FDG PET/CT. METHODS: Thirty-five PerAF patients were compared to age and sex matched ParAF group with baseline 18F-FDG PET/CT scans prior to radiofrequency catheter ablation (RFCA) in the prospective case-control study. High-fat and low-carbohydrate diet and prolonged fast (HFLC+Fast) was applied to all AF patients before PET/CT. Then 22 AF patients with positive right atrial (RA) wall FDG uptake (HFLC+Fast) were randomly selected and underwent HFLC+Fast+heparin the next day. The CHA2DS2-VASc score was calculated to evaluate the risk of stroke. Clinical data, ECG, echocardiography, and atrial 18F-FDG uptake were compared. RESULTS: PerAF patients had significantly higher probability of RA wall positive FDG uptake and higher SUVmax than ParAF group [91.4% VS. 28.6%, P < 0.001; SUVmax: 4.10(3.20-4.90) VS. 2.60(2.40-3.10), P < 0.001]. Multivariate logistic regression analyses demonstrated that RA wall SUVmax was the independent influencing factor of PerAF (OR = 1.80, 95%CI 1.02-3.18, P = 0.04). In 22 AF patients with RA wall positive FDG uptake (HFLC+Fast), the "HFLC+Fast+Heparin" method did not significantly change RA wall FDG uptake evaluated by either quantitative analysis or visual analysis. High CHA2DS2-VASc score group had higher RA wall 18F-FDG uptake [3.35 (2.70, 4.50) vs, 2.8 (2.4, 3.1) P = 0.01]. CONCLUSIONS: RA wall FDG positive uptake was present mainly in PerAF. A higher RA wall 18F-FDG uptake was an independent influencing factor of PerAF. RA wall FDG uptake based on 18F-FDG PET/CT may indicate pathological inflammation. TRIAL REGISTRATION: http://www.chictr.org.cn , ChiCTR2000038288.

Recent Progress on Phase Engineering of Nanomaterials.

As a key structural parameter, phase depicts the arrangement of atoms in materials. Normally, a nanomaterial exists in its thermodynamically stable crystal phase. With the development of nanotechnology, nanomaterials with unconventional crystal phases, which rarely exist in their bulk counterparts, or amorphous phase have been prepared using carefully controlled reaction conditions. Together these methods are beginning to enable phase engineering of nanomaterials (PEN), i.e., the synthesis of nanomaterials with unconventional phases and the transformation between different phases, to obtain desired properties and functions. This Review summarizes the research progress in the field of PEN. First, we present representative strategies for the direct synthesis of unconventional phases and modulation of phase transformation in diverse kinds of nanomaterials. We cover the synthesis of nanomaterials ranging from metal nanostructures such as Au, Ag, Cu, Pd, and Ru, and their alloys; metal oxides, borides, and carbides; to transition metal dichalcogenides (TMDs) and 2D layered materials. We review synthesis and growth methods ranging from wet-chemical reduction and seed-mediated epitaxial growth to chemical vapor deposition (CVD), high pressure phase transformation, and electron and ion-beam irradiation. After that, we summarize the significant influence of phase on the various properties of unconventional-phase nanomaterials. We also discuss the potential applications of the developed unconventional-phase nanomaterials in different areas including catalysis, electrochemical energy storage (batteries and supercapacitors), solar cells, optoelectronics, and sensing. Finally, we discuss existing challenges and future research directions in PEN.

Identification of lncRNAs associated with uterine corpus endometrial cancer prognosis based on the competing endogenous RNA network.

Uterine Corpus Endometrial Carcinoma (UCEC) is one of the major malignant tumors of the female reproductive system. However, there are limitations in the currently available diagnostic approaches for UCEC. Long non-coding RNAs (lncRNAs) play important roles in regulating biological processes as competitive endogenous RNA (ceRNA) in tumors. To study the potential of lncRNAs as non-invasive diagnostic tumor markers, RNA-sequencing dataset of UCEC patients from The Cancer Genome Atlas was used to identify differentially expressed genes. A lncRNA-miRNA-mRNA ceRNA network was constructed by differentially expressed lncRNAs, miRNAs and miRNAs. Pathway enrichment and functional analysis for the mRNAs in the constructed ceRNA network provide the direction of future research for UCEC by demonstrating the most affected processes and pathways. Seven potential lncRNA biomarkers (C20orf56, LOC100144604, LOC100190940, LOC151534, LOC727677, FLJ35390, LOC158572) were validated in UCEC patients by quantitative real-time PCR. Notably, LOC100190940 and LOC158572 were identified as novel RNA molecules with unknown functions. Receiver operating characteristic (ROC) curve analysis demonstrated that the combined 7 lncRNAs had a high diagnostic value for UCEC patients with area under curve (AUC) of 0.941 (95% CI: 0.875-0.947). Our study highlights the potential of the validated 7 lncRNAs panel as diagnostic biomarkers in UCEC, providing new insights into the UCEC pathogenesis.

Versatile synthesis of nano-icosapods via cation exchange for effective photocatalytic conversion of biomass-relevant alcohols.

Branched metal chalcogenide nanostructures with well-defined composition and configuration are appealing photocatalysts for solar-driven organic transformations. However, precise design and controlled synthesis of such nanostructures still remain a great challenge. Herein, we report the construction of a variety of highly symmetrical metal sulfides and heterostructured icosapods based on them, in which twenty branches were radially grown in spatially ordered arrangement, with a high degree of structure homogeneity. Impressively, the as-obtained CdS-PdxS icosapods manifest a significantly improved photocatalytic activity for the selective oxidation of biomass-relevant alcohols into corresponding aldehydes coupled with H2 evolution under visible-light irradiation (>420 nm), and the apparent quantum yield of the benzyl alcohol reforming can be achieved as high as 31.4% at 420 nm. The photoreforming process over the CdS-PdxS icosapods is found to be directly triggered by the photogenerated electrons and holes without participation of radicals. The enhanced photocatalytic performance is attributed to the fast charge separation and abundant active sites originating from the well-defined configuration and spatial organization of the components in the branched heterostructures.

Mineralization of Few-Layer Graphene Made It Bioavailable in Chlamydomonas reinhardtii.

Numerous studies have emphasized the toxicity of graphene-based nanomaterials to algae, however, the fundamental behavior and processes of graphene in biological hosts, including its transportation, metabolization, and bioavailability, are still not well understood. As photosynthetic organisms, algae are key contributors to carbon fixation and may play an important role in the fate of graphene. This study investigated the biological fate of 14C-labeled few-layer graphene (14C-FLG) in Chlamydomonas reinhardtii (C. reinhardtii). The results showed that 14C-FLG was taken up by C. reinhardtii and then translocated into its chloroplast. Metabolomic analysis revealed that 14C-FLG altered the metabolic profiles (including sugar metabolism, fatty acid, and tricarboxylic acid cycle) of C. reinhardtii, which promoted the photosynthesis of C. reinhardtii and then enhanced their growth. More importantly, the internalized 14C-FLG was metabolized into 14CO2, which was then used to participate in the metabolic processes required for life. Approximately 61.63%, 25.31%, and 13.06% of the total radioactivity (from 14CO2) was detected in carbohydrates, lipids, and proteins of algae, respectively. Overall, these results reveal the role of algae in the fate of graphene and highlight the potential of available graphene in bringing biological effects to algae, which helps to better assess the environmental risks of graphene.

Phase-dependent growth of Pt on MoS2 for highly efficient H2 evolution.

Crystal phase is a key factor determining the properties, and hence functions, of two-dimensional transition-metal dichalcogenides (TMDs)1,2. The TMD materials, explored for diverse applications3-8, commonly serve as templates for constructing nanomaterials3,9 and supported metal catalysts4,6-8. However, how the TMD crystal phase affects the growth of the secondary material is poorly understood, although relevant, particularly for catalyst development. In the case of Pt nanoparticles on two-dimensional MoS2 nanosheets used as electrocatalysts for the hydrogen evolution reaction7, only about two thirds of Pt nanoparticles were epitaxially grown on the MoS2 template composed of the metallic/semimetallic 1T/1T' phase but with thermodynamically stable and poorly conducting 2H phase mixed in. Here we report the production of MoS2 nanosheets with high phase purity and show that the 2H-phase templates facilitate the epitaxial growth of Pt nanoparticles, whereas the 1T' phase supports single-atomically dispersed Pt (s-Pt) atoms with Pt loading up to 10 wt%. We find that the Pt atoms in this s-Pt/1T'-MoS2 system occupy three distinct sites, with density functional theory calculations indicating for Pt atoms located atop of Mo atoms a hydrogen adsorption free energy of close to zero. This probably contributes to efficient electrocatalytic H2 evolution in acidic media, where we measure for s-Pt/1T'-MoS2 a mass activity of 85 ± 23 A [Formula: see text] at the overpotential of -50 mV and a mass-normalized exchange current density of 127 A [Formula: see text] and we see stable performance in an H-type cell and prototype proton exchange membrane electrolyser operated at room temperature. Although phase stability limitations prevent operation at high temperatures, we anticipate that 1T'-TMDs will also be effective supports for other catalysts targeting other important reactions.

On-chip electrocatalytic microdevices.

On-chip electrocatalytic microdevices (OCEMs) are an emerging electrochemical platform specialized for investigating nanocatalysts at the microscopic level. The OCEM platform allows high-precision electrochemical measurements at the individual nanomaterial level and, more importantly, offers unique perspectives inaccessible with conventional electrochemical methods. This protocol describes the critical concepts, experimental standardization, operational principles and data analysis of OCEMs. Specifically, standard protocols for the measurement of the electrocatalytic hydrogen evolution reaction of individual 2D nanosheets are introduced with data validation, interpretation and benchmarking. A series of factors (e.g., the exposed area of material, the choice of passivation layer and current leakage) that could have effects on the accuracy and reliability of measurement are discussed. In addition, as an example of the high adaptability of OCEMs, the protocol for in situ electrical transport measurement is detailed. We believe that this protocol will promote the general adoption of the OCEM platform and inspire further development in the near future. This protocol requires essential knowledge in chemical synthesis, device fabrication and electrochemistry.

Synthesis of 2H/fcc-Heterophase AuCu Nanostructures for Highly Efficient Electrochemical CO2 Reduction at Industrial Current Densities.

Structural engineering of nanomaterials offers a promising way for developing high-performance catalysts toward catalysis. However, the delicate modulation of thermodynamically unfavorable nanostructures with unconventional phases still remains a challenge. Here, the synthesis of hierarchical AuCu nanostructures is reported with hexagonal close-packed (2H-type)/face-centered cubic (fcc) heterophase, high-index facets, planar defects (e.g., stacking faults, twin boundaries, and grain boundaries), and tunable Cu content. The obtained 2H/fcc Au99 Cu1 hierarchical nanosheets exhibit excellent performance for the electrocatalytic CO2 reduction to produce CO, outperforming the 2H/fcc Au91 Cu9 and fcc Au99 Cu1 . The experimental results, especially those obtained by in-situ differential electrochemical mass spectroscopy and attenuated total reflection Fourier-transform infrared spectroscopy, suggest that the enhanced catalytic performance of 2H/fcc Au99 Cu1 arises from the unconventional 2H/fcc heterophase, high-index facets, planar defects, and appropriate alloying of Cu. Impressively, the 2H/fcc Au99 Cu1 shows CO Faradaic efficiencies of 96.6% and 92.6% at industrial current densities of 300 and 500 mA cm-2 , respectively, as well as good durability, placing it among the best CO2 reduction electrocatalysts for CO production. The atomically structural regulation based on phase engineering of nanomaterials (PEN) provides an avenue for the rational design and preparation of high-performance electrocatalysts for various catalytic applications.

Reversible Semimetal-Semiconductor Transition of Unconventional-Phase WS2 Nanosheets.

Phase transition with band gap modulation of materials has gained intensive research attention due to its various applications, including memories, neuromorphic computing, and transistors. As a powerful strategy to tune the crystal phase of transition-metal dichalcogenides (TMDs), the phase transition of TMDs provides opportunities to prepare new phases of TMDs for exploring their phase-dependent property, function, and application. However, the previously reported phase transition of TMDs is mainly irreversible. Here, we report a reversible phase transition in the semimetallic 1T'-WS2 driven by proton intercalation and deintercalation, resulting in a newly discovered semiconducting WS2 with a novel unconventional phase, denoted as the 1T'd phase. Impressively, an on/off ratio of >106 has been achieved during the phase transition of WS2 from the semimetallic 1T' phase to the semiconducting 1T'd phase. Our work not only provides a unique insight into the phase transition of TMDs via proton intercalation but also opens up possibilities to tune their physicochemical properties for various applications.

Seeded Synthesis of Hollow PdSn Intermetallic Nanomaterials for Highly Efficient Electrocatalytic Glycerol Oxidation.

Intermetallic nanomaterials have shown promising potential as high-performance catalysts in various catalytic reactions due to their unconventional crystal phases with ordered atomic arrangements. However, controlled synthesis of intermetallic nanomaterials with tunable crystal phases and unique hollow morphologies remains a challenge. Here, a seeded method is developed to synthesize hollow PdSn intermetallic nanoparticles (NPs) with two different intermetallic phases, that is, orthorhombic Pd2 Sn and monoclinic Pd3 Sn2 . Benefiting from the rational regulation of the crystal phase and morphology, the obtained hollow orthorhombic Pd2 Sn NPs deliver excellent electrocatalytic performance toward glycerol oxidation reaction (GOR), outperforming solid orthorhombic Pd2 Sn NPs, hollow monoclinic Pd3 Sn2 NPs, and commercial Pd/C, which places it among the best reported Pd-based GOR electrocatalysts. The reaction mechanism of GOR using the hollow orthorhombic Pd2 Sn as the catalyst is investigated by operando infrared reflection absorption spectroscopy, which reveals that the hollow orthorhombic Pd2 Sn catalyst cleaves the CC bond more easily compared to the commercial Pd/C. This work can pave an appealing route to the controlled synthesis of diverse novel intermetallic nanomaterials with hollow morphology for various promising applications.

Co-exposure of polycarbonate microplastics aggravated the toxic effects of imidacloprid on the liver and gut microbiota in mice.

The joint toxicity of microplastics (MPs) and pesticides may be different from MPs or pesticides individually, however, the information about the combined toxicity of MPs and pesticides is not well understood. Herein, we investigated the joint toxicity of polycarbonate (PC) MPs and imidacloprid (IMI) on mice. After orally exposure for 4 weeks, PC and/or IMI lowered the body weight gain of mice. Single exposure of IMI induced the tissue damage in liver by disturbing the redox homeostasis, and PC significantly aggravated the imbalance of redox homeostasis by facilitating the accumulation of IMI in liver. Additionally, compared to single exposure of PC or IMI, PC+IMI exposure caused more severe damage to the gut microstructure and microbial diversity. Several key metabolic pathways, especially the lipid metabolism, were significantly affected. Overall, these findings provide new insight into understanding the potential risk of co-exposure of microplastics and pesticides to animal and human health.

Epitaxial growth of highly symmetrical branched noble metal-semiconductor heterostructures with efficient plasmon-induced hot-electron transfer.

Epitaxial growth is one of the most commonly used strategies to precisely tailor heterostructures with well-defined compositions, morphologies, crystal phases, and interfaces for various applications. However, as epitaxial growth requires a small interfacial lattice mismatch between the components, it remains a challenge for the epitaxial synthesis of heterostructures constructed by materials with large lattice mismatch and/or different chemical bonding, especially the noble metal-semiconductor heterostructures. Here, we develop a noble metal-seeded epitaxial growth strategy to prepare highly symmetrical noble metal-semiconductor branched heterostructures with desired spatial configurations, i.e., twenty CdS (or CdSe) nanorods epitaxially grown on twenty exposed (111) facets of Ag icosahedral nanocrystal, albeit a large lattice mismatch (more than 40%). Importantly, a high quantum yield (QY) of plasmon-induced hot-electron transferred from Ag to CdS was observed in epitaxial Ag-CdS icosapods (18.1%). This work demonstrates that epitaxial growth can be achieved in heterostructures composed of materials with large lattice mismatches. The constructed epitaxial noble metal-semiconductor interfaces could be an ideal platform for investigating the role of interfaces in various physicochemical processes.