A tumor-promotional molecular axis CircMAPKBP1/miR-17-3p/TGFß2 activates autophagy pathway to drive tongue squamous cell carcinoma cisplatin chemoresistance.

Platinum-based chemotherapy is the first-line treatment for tongue squamous cell carcinoma (TSCC), but most patients rapidly develop resistance. Circular RNAs (circRNAs) are a class of critical regulators in the pathogenesis of several tumors, but their role in cisplatin resistance in TSCC has not been fully elucidated. Here we found that circMAPKBP1 was enriched in cisplatin resistant TSCC cells and was closely associated with enhanced autophagic activity. Functionally, silencing circMAPKBP1 significantly restored the chemosensitivity of cisplatin-resistant TSCC cells both in vitro and in vivo by suppressing autophagy. Mechanistically, circMAPKBP1 enhanced cisplatin sensitivity through the miR-17-3p/TGFß2 axis by activating autophagy pathway. Data from clinical studies revealed that high expression of circMAPKBP1 and TGFß2 was closely linked to a poor outcome in TSCC patients. We thus concluded that circMAPKBP1 is a tumor promoting factor and confers cisplatin sensitivity by activating the miR-17-3p/TGFß2 axis-mediated autophagy. We propose that circMAPKBP1 may be a potential therapeutic target for TSCC.

Reviving Multivalent-metal Anodes in Simple Salt Electrolytes via Component Modifier Design.

Using combinatory electrolyte blends represents an imperative avenue to achieve good magnesium (Mg)-metal anode compatibility and commercial feasibility in fields of promising rechargeable Mg batteries. However, fundamental challenges of how to manipulate component modifier reactivity on molecule level still remain to be solved. Here, molecular structure design concepts towards seeking bromophenyl complex-based component modifiers has been proposed according to implications of electron-donating and/or electron-withdrawing substituents on Br-C bond dissociation reactivity. Exceptional Mg electro-plating/stripping properties (a stable cycle life of 250 days in Mg//Cu asymmetric cells) have been firstly achieved in a simple salt electrolyte with 1-(3-bromophenyl)-N,N-dimethylmethanamine (BPDMA) as optimal component modifier. Comprehensive analyses disclose the unique electrochemically-active Br-containing ion-pairs formation, such as [(Mg2+)2(TFSI-)Br-]2+ and [(Mg2+)2(TFSI-)(Br-)(G2)2]2+, which results in the much thinner Br- containing and organic-inorganic mixed interphases on Mg-metal anodes. Furthermore, conventional MgSO4-based electrolytes and even calcium (Ca)-ion electrolytes can also be revived by similar strategy, demonstrating its generality and superiority.

Probing the structure and dynamics of the heterocyclic PAH xanthene and its water complexes with infrared and microwave spectroscopy.

To assess the presence of oxygen-containing polycyclic aromatic hydrocarbons (OPAHs) in the interstellar medium and understand how water aggregates on an OPAH surface, we present a comprehensive gas-phase spectroscopy investigation of the OPAH xanthene (C13H10O) and its complexes with water using IR-UV ion dip spectroscopy and chirped-pulse Fourier transform microwave spectroscopy. The infrared spectrum of xanthene shows weak features at 3.42, 3.43, and 3.47 µm, which have been suggested to partly originate from vibrational modes of PAHs containing sp3 hybridized carbon atoms, in agreement with the molecular structure of xanthene. The high resolution of rotational spectroscopy reveals a tunneling splitting of the rotational transitions, which can be explained with an out-of-plane bending motion of the two lateral benzene rings of xanthene. The nature of the tunnelling motion is elucidated by observing a similar splitting pattern in the rotational transitions of the singly-substituted 13C isotopologues. The rotational spectroscopy investigation is extended to hydrates of xanthene with up to four water molecules. Different xanthene-water binding motifs are observed based on the degree of hydration, with O-H⋯π interactions becoming preferred over O-H⋯Oxanthene interactions as the degree of hydration increases. A structural comparison with water complexes of related molecular systems highlights the impact of the substrate's shape and chemical composition on the arrangement of the surrounding water molecules.

Stress-Induced Martensitic Transformation in Na3YCl6.

Martensitic transformation with volume expansion plays a crucial role in enhancing the mechanical properties of steel and partially stabilized zirconia. We believe that a similar concept could be applied to unexplored nonoxide materials. Herein, we report the stress-induced martensitic transformation of monoclinic Na3YCl6 with an ∼3.4% expansion. In situ synchrotron X-ray diffraction and atomistic simulations showed that anisotropic crystallographic transformation from monoclinic to rhombohedral Na3YCl6 occurs exclusively under uniaxial pressure; no effect is observed under hydrostatic pressure conditions. The uniaxially pressed powder compact of monoclinic Na3YCl6 showed a large indentation impression and low Young's modulus, in contrast to its high bulk modulus, suggesting that these unique mechanical properties are induced by the martensitic transformation.

Predictive model for prolonged hospital stay risk after gastric cancer surgery.

Background: Prolonged postoperative hospital stay following gastric cancer (GC) surgery is an important risk factor affecting patients' mood and increasing complications. We aimed to develop a nomogram to predict risk factors associated with prolonged postoperative length of stay (PLOS) in patients undergoing gastric cancer resection. Methods: Data were collected from 404 patients. The least absolute shrinkage and selection operator (LASSO) was used for variable screening, and a nomogram was designed. The nomogram performance was evaluated by the area under the receiver operating characteristic curve (AUC). The consistency between the predicted and actual values was evaluated via a calibration map, and the clinical application value was evaluated via decision curve analysis (DCA) and clinical impact curve analysis (CICA). Results: A total of 404 patients were included in this study. Among these patients, 287 were assigned to the training cohort, and 117 were assigned to the validation cohort. According to the PLOS quartile distance, 103 patients were defined as having prolonged PLOS. LASSO regression and logistic multivariate analysis revealed that 4 clinical characteristics, the neutrophil-lymphocyte ratio (NLR) on postoperative day one, the NLR on postoperative day three, the preoperative prognostic nutrition index and the first time anal exhaust was performed, were associated with the PLOS and were included in the construction of the nomogram. The AUC of the nomogram prediction model was 0.990 for the training set and 0.983 for the validation set. The calibration curve indicated good correlation between the predicted results and the actual results. The Hosmer-Lemeshow test revealed that the P values for the training and validation sets were 0.444 and 0.607, respectively, indicating that the model had good goodness of fit. The decision curve analysis and clinical impact curve of this model showed good clinical practicability for both cohorts. Conclusion: We explored the risk factors for prolonged PLOS in GC patients via the enhanced recovery after surgery (ERAS) program and developed a predictive model. The designed nomogram is expected to be an accurate and personalized tool for predicting the risk and prognosis of PLOS in GC patients via ERAS measures.

Colorimetric and Fluorometric Determination of Fluoride in Tetrahydrofuran and Dimethyl Sulfoxide Using a 4-Hydroxypyrene Probe.

F- ions (fluoride ions) are crucial in various chemical waste and environmental safety contexts. However, excessive fluoride exposure can pose a threat to human well-being. In this study, a simple 4-substituted pyrene derivative known as 4-hydroxypyrene (4-PyOH) was designed as a colorimetric probe for detecting F- through the formation of hydrogen bonds between F- and a hydroxyl group. The probe 4-PyOH exhibited exceptional sensitivity and selectivity towards F- ions and was successfully utilized as test strips for detecting F- ions in organic solvents. The detection limit reached an impressively low level of 3.06 × 10-7 M in the organic solvent. The recognition mechanism was confirmed through 1H NMR titration.

Facile Synthesis of Organic-Inorganic Hybrid Heterojunctions of Glycolated Conjugated Polymer-TiO2-X for Efficient Photocatalytic Hydrogen Evolution.

The utilization of the organic-inorganic hybrid photocatalysts for water splitting has gained significant attention due to their ability to combine the advantages of both materials and generate synergistic effects. However, they are still far from practical application due to the limited understanding of the interactions between these two components and the complexity of their preparation process. Herein, a facial approach by combining a glycolated conjugated polymer with a TiO2-X mesoporous sphere to prepare high-efficiency hybrid photocatalysts is presented. The functionalization of conjugated polymers with hydrophilic oligo (ethylene glycol) side chains can not only facilitate the dispersion of conjugated polymers in water but also promote the interaction with TiO2-X forming stable heterojunction nanoparticles. An apparent quantum yield of 53.3% at 365 nm and a hydrogen evolution rate of 35.7 mmol h-1 g-1 is achieved by the photocatalyst in the presence of Pt co-catalyst. Advanced photophysical studies based on femtosecond transient absorption spectroscopy and in situ, XPS analyses reveal the charge transfer mechanism at type II heterojunction interfaces. This work shows the promising prospect of glycolated polymers in the construction of hybrid heterojunctions for photocatalytic hydrogen production and offers a deep understanding of high photocatalytic performance by such heterojunction photocatalysts.

Clinically relevant immune subtypes based on alternative splicing landscape of immune-related genes for lung cancer advanced PPPM approach.

Background: Alternative splicing (AS) occurs in the process of gene post-transcriptional process, which is very important for the correct synthesis and function of protein. The change of AS pattern may lead to the change of expression level or function of lung cancer-related genes, and then affect the occurrence and development of lung cancers. The specific AS pattern might be used as a biomarker for early warning and prognostic assessment of a cancer in the framework of predictive, preventive, and personalized medicine (PPPM; 3PM). AS events of immune-related genes (IRGs) were closely associated with tumor progression and immunotherapy. We hypothesize that IRG-AS events are significantly different in lung adenocarcinomas (LUADs) vs. controls or in lung squamous cell carcinomas (LUSCs) vs. controls. IRG-AS alteration profiling was identified to construct IRG-differentially expressed AS (IRG-DEAS) signature models. Study on the selective AS events of specific IRGs in lung cancer patients might be of great significance for further exploring the pathogenesis of lung cancer, realizing early detection and effective monitoring of lung cancer, finding new therapeutic targets, overcoming drug resistance, and developing more effective therapeutic strategies, and better used for the prediction, diagnosis, prevention, and personalized medicine of lung cancer. Methods: The transcriptomic, clinical, and AS data of LUADs and LUSCs were downloaded from TCGA and its SpliceSeq databases. IRG-DEAS events were identified in LUAD and LUSC, followed by their functional characteristics, and overall survival (OS) analyses. OS-related IRG-DEAS prognostic models were constructed for LUAD and LUSC with Lasso regression, which were used to classify LUADs and LUSCs into low- and high-risk score groups. Furthermore, the immune cell distribution, immune-related scores, drug sensitivity, mutation status, and GSEA/GSVA status were analyzed between low- and high-risk score groups. Also, low- and high-immunity clusters and AS factor (SF)-OS-related-AS co-expression network and verification of cell function of CELF6 were analyzed in LUAD and LUSC. Results: Comprehensive analysis of transcriptomic, clinical, and AS data of LUADs and LUSCs identified IRG-AS events in LUAD (n = 1607) and LUSC (n = 1656), including OS-related IRG-AS events in LUAD (n = 127) and LUSC (n = 105). A total of 66 IRG-DEAS events in LUAD and 89 IRG-DEAS events in LUSC were identified compared to controls. The overlapping analysis between IRG-DEASs and OS-related IRG-AS events revealed 14 OS-related IRG-DEAS events for LUAD and 16 OS-related IRG-DEAS events for LUSC, which were used to identify and optimize a 12-OS-related-IRG-DEAS signature prognostic model for LUAD and an 11-OS-related-IRG-DEAS signature prognostic model for LUSC. These two prognostic models effectively divided LUAD or LUSC samples into low- and high-risk score groups that were closely associated with OS, clinical characteristics, and tumor immune microenvironment, with significant gene sets and pathways enriched in the two groups. Moreover, weighted gene co-expression network (WGCNA) and nonnegative matrix factorization method (NMF) analyses identified four OS-relevant subtypes of LUAD and six OS-relevant subtypes of LUSC, and ssGSEA identified five immunity-relevant subtypes of LUAD and five immunity-relevant subtypes of LUSC. Interestingly, splicing factors-OS-related-AS network revealed hub molecule CELF6 was significantly related to the malignant phenotype in lung cancer cells. Conclusions: This study established two reliable IRG-DEAS signature prognostic models and constructed interesting splicing factor-splicing event networks in LUAD and LUSC, which can be used to construct clinically relevant immune subtypes, patient stratification, prognostic prediction, and personalized medical services in the PPPM practice. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00366-4.

Transcription directionality is licensed by Integrator at active human promoters.

A universal characteristic of eukaryotic transcription is that the promoter recruits RNA polymerase II (RNAPII) to produce both precursor mRNAs (pre-mRNAs) and short unstable promoter upstream transcripts (PROMPTs) toward the opposite direction. However, how the transcription machinery selects the correct direction to produce pre-mRNAs is largely unknown. Here, through multiple acute auxin-inducible degradation systems, we show that rapid depletion of an RNAPII-binding protein complex, Integrator, results in robust PROMPT accumulation throughout the genome. Interestingly, the accumulation of PROMPTs is compensated by the reduction of pre-mRNA transcripts in actively transcribed genes. Consistently, Integrator depletion alters the distribution of polymerase between the sense and antisense directions, which is marked by increased RNAPII-carboxy-terminal domain Tyr1 phosphorylation at PROMPT regions and a reduced Ser2 phosphorylation level at transcription start sites. Mechanistically, the endonuclease activity of Integrator is critical to suppress PROMPT production. Furthermore, our data indicate that the presence of U1 binding sites on nascent transcripts could counteract the cleavage activity of Integrator. In this process, the absence of robust U1 signal at most PROMPTs allows Integrator to suppress the antisense transcription and shift the transcriptional balance in favor of the sense direction.

Nitrogen-Rich Molybdenum Nitride Synthesized in a Crucible under Air.

The triple bond in N2 is significantly stronger than the double bond in O2, meaning that synthesizing nitrogen-rich nitrides typically requires activated nitrogen precursors, such as ammonia, plasma-cracked atomic nitrogen, or high-pressure N2. Here, we report a synthesis of nitrogen-rich nitrides under ambient pressure and atmosphere. Using Na2MoO4 and dicyandiamide precursors, we synthesized nitrogen-rich γ-Mo2N3 in an alumina crucible under an ambient atmosphere, heated in a box furnace between 500 and 600 °C. Byproducts of this metathesis reaction include volatile gases and solid Na(OCN), which can be washed away with water. X-ray diffraction and neutron diffraction showed Mo2N3 with a rock salt structure having cation vacancies, with no oxygen incorporation, in contrast to the more common nitrogen-poor rock salt Mo2N with anion vacancies. Moreover, an increase in temperature to 700 °C resulted in molybdenum oxynitride, Mo0.84N0.72O0.27. This work illustrates the potential for dicyandiamide as an ambient-temperature metathesis precursor for an increased effective nitrogen chemical potential under ambient conditions. The classical experimental setting often used for solid-state oxide synthesis, therefore, has the potential to expand the nitride chemistry.

First description of the females of Qinorapalaqinlingana Chou & Wang, 1995 (Lepidoptera, Lycaenidae) from Shaanxi and Sichuan Provinces, western China.

Background: The family Lycaenidae is a widely distributed and species-rich group with approximately 5300 described species. The rare genus Qinorapala Chou & Wang, with Q.qinlingana Chou & Wang as its type species was established as monotypic. In the original description, Q.qinlingana was described from a male holotype; the female remained unknown. To date, the genus is only recorded from the Qinling Mountains (Shaanxi and Gansu Provinces). In this study, two female specimens, from Shaanxi Province and western Sichuan Province (bordering Yunnan Province) are described and illustrated for the first time. New information: Female specimens of Q.qinlingana from Shaanxi and Sichuan are described for the first time. The species' distribution is updated and a distribution map is provided.

Gas-Phase Characterization of Adipic Acid, 6-Hydroxycaproic Acid, and Their Thermal Decomposition Products by Rotational Spectroscopy.

We report the spectroscopic investigation of two bifunctional aliphatic carboxylic acids, namely, adipic acid and 6-hydroxycaproic acid, in the gas phase by combining high-resolution rotational spectroscopy and supersonic expansions. Their pure rotational spectra were successfully identified and characterized. However, due to the low thermal stability of these two chemicals, the measured rotational spectra were significantly congested with transitions corresponding to their decomposition products upon heating. We observed cyclopentanone and adipic anhydride in the spectrum of adipic acid and ε-caprolactone and its monohydrate in the spectrum of 6-hydroxycaproic acid. On the basis of the distinct fingerprints of both carboxylic acids and a series of their decomposition products, the spectra were analyzed in a time-segmented manner. This provides valuable insights into the thermal decomposition mechanisms of these two samples over time, which highlights the robustness of microwave spectroscopy as a potent tool for analyzing complex chemical mixtures in a species-, isomer-, and conformer-selective way.

Unravelling the interplay of local structure and valence transitions in Ce-doped CaYAlO4 luminescent materials.

Cerium has been widely used as a dopant in luminescent materials due to its unique electronic configurations. It is generally anticipated that the luminescence properties of rare-earth-doped materials are closely related to the local environment of activators, especially for Ce3+ . In addition, it is convenient to modulate its emission wavelength by adjusting the composition and structure. In this study, we systematically analyzed the microstructure of the Ce-doped CaYAlO4 system at atomic resolution. The quantitive results indicated that the structure distortion greatly influenced the valence state of the Ce dopant, which is critical to its luminescence efficiency. In addition, valence variations also exist from surface to inner structure due to the big distortion area around the surface. Our results unravel the interplay of local structure and valence transitions in Ce-doped aluminate phosphors, which has the potential to be applied in other luminescent materials.

Out-of-set association analysis of lung cancer drugs and symptoms based on clinical case data mining.

BACKGROUND: There are 1.8 million lung cancer deaths worldwide, accounting for 18% of global cancer deaths, including 710,000 in China, accounting for 23.8% of all cancer deaths in China. OBJECTIVE: To explore the out-of-set association rules of lung cancer symptoms and drugs through text mining of traditional Chinese medicine (TCM) treatment of lung cancer, and form medical case analysis to analyze the experience of TCM syndrome differentiation in its treatment. METHODS: The medical records of all patients diagnosed with lung cancer in Nanjing Chest Hospital from January to December 2018 were collected, and the out-of-set association analysis was performed using the MedCase v5.2 TCM clinical scientific research auxiliary platform based on the frequent pattern growth enhanced association analysis algorithm. RESULTS: In terms of TCM treatment of lung cancer, the clinical symptoms with high correlation included cough, expectoration, chest distress, and white phlegm; and the drugs with high correlation included Pinellia ternata, licorice root, white Atractylodes rhizome, and Radix Ophiopogonis; with the prescriptions based on Erchen and Maimendong decoctions. CONCLUSION: This analytical study of the medical cases of TCM treatment for lung cancer was performed using data mining techniques, and the out-of-set association rules between clinical symptoms and drugs were analyzed, including the understanding of lung cancer in TCM. Moreover, the essence of experience in drug use was gathered, providing significant scientific guidance for the clinical treatment of lung cancer.

ZmELF6-ZmPRR37 module regulates maize flowering and salt response.

The control of flowering time in maize is crucial for reproductive success and yield, and it can be influenced by environmental stresses. Using the approaches of Ac/Ds transposon and transposable element amplicon sequencing techniques, we identified a Ds insertion mutant in the ZmPRR37 gene. The Ds insertion showed a significant correlation with days to anthesis. Further research indicated that ZmPRR37-CR knockout mutants exhibited early flowering, whereas ZmPRR37-overexpression lines displayed delayed flowering compared to WT under long-day (LD) conditions. We demonstrated that ZmPRR37 repressed the expression of ZmNF-YC2 and ZmNF-YA3 to delay flowering. Association analysis revealed a significant correlation between flowering time and a SNP2071-C/T located upstream of ZmPRR37. The SNP2071-C/T impacted the binding capacity of ZmELF6 to the promoter of ZmPRR37. ZmELF6 also acted as a flowering suppressor in maize under LD conditions. Notably, our study unveiled that ZmPRR37 can enhance salt stress tolerance in maize by directly regulating the expression of ABA-responsive gene ZmDhn1. ZmDhn1 negatively regulated maize salt stress resistance. In summary, our findings proposed a novel pathway for regulating photoperiodic flowering and responding to salt stress based on ZmPRR37 in maize, providing novel insights into the integration of abiotic stress signals into floral pathways.

Dissolution enables dolomite crystal growth near ambient conditions.

Crystals grow in supersaturated solutions. A mysterious counterexample is dolomite CaMg(CO3)2, a geologically abundant sedimentary mineral that does not readily grow at ambient conditions, not even under highly supersaturated solutions. Using atomistic simulations, we show that dolomite initially precipitates a cation-disordered surface, where high surface strains inhibit further crystal growth. However, mild undersaturation will preferentially dissolve these disordered regions, enabling increased order upon reprecipitation. Our simulations predict that frequent cycling of a solution between supersaturation and undersaturation can accelerate dolomite growth by up to seven orders of magnitude. We validated our theory with in situ liquid cell transmission electron microscopy, directly observing bulk dolomite growth after pulses of dissolution. This mechanism explains why modern dolomite is primarily found in natural environments with pH or salinity fluctuations. More generally, it reveals that the growth and ripening of defect-free crystals can be facilitated by deliberate periods of mild dissolution.

A Naïve Phage Display Library-Derived Nanobody Neutralizes SARS-CoV-2 and Three Variants of Concern.

Background: The emergence of the coronavirus disease 2019 (COVID-19) pandemic and the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VOCs) requires the continuous development of safe, effective, and affordable prevention and therapeutics. Nanobodies have demonstrated antiviral activity against a variety of viruses, providing a new candidate for the prevention and treatment of SARS-CoV-2 and its variants. Methods: SARS-CoV-2 glycoprotein spike 1 subunit (S1) was selected as the target antigen for nanobody screening of a naïve phage display library. We obtained a nanobody, named Nb-H6, and then determined its affinity, inhibition, and stability by ELISA, Competitive ELISA, and Biolayer Interferometry (BLI). Infection assays of authentic and pseudotyped SARS-CoV-2 were performed to evaluate the neutralization of Nb-H6. The structure and mechanism of action were investigated by AlphaFold, docking, and residue mutation assays. Results: We isolated and characterized a nanobody, Nb-H6, which exhibits a broad affinity for S1 and the receptor binding domain (RBD) of SARS-CoV-2, or Alpha (B.1.1.7), Delta (B.1.617.2), Lambda (C.37), and Omicron (BA.2 and BA.5), and blocks receptor angiotensin-converting enzyme 2 (ACE2) binding. Moreover, Nb-H6 can retain its binding capability after pH or thermal treatment and effectively neutralize both pseudotyped and authentic SARS-CoV-2, as well as VOC Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (BA.2 and BA.5) pseudoviruses. We also confirmed that Nb-H6 binds two distinct amino acid residues of the RBD, preventing SARS-CoV-2 from interacting with the host receptor. Conclusion: Our study highlights a novel nanobody, Nb-H6, that may be useful therapeutically in SARS-CoV-2 and VOC outbreaks and pandemics. These findings also provide a molecular foundation for further studies into how nanobodies neutralize SARS-CoV-2 and variants and imply potential therapeutic targets for the treatment of COVID-19.

LINC00955 suppresses colorectal cancer growth by acting as a molecular scaffold of TRIM25 and Sp1 to Inhibit DNMT3B-mediated methylation of the PHIP promoter.

BACKGROUND: Long non-coding RNAs play an important role in the development of colorectal cancer (CRC), while many CRC-related lncRNAs have not yet been identified. METHODS: The relationship between the expression of LINC00955 (Long Intergenic Non-protein Coding RNA 955) and the prognosis of colorectal cancer patients was analyzed using the sequencing results of the TCGA database. LINC00955 expression levels were measured using qRT-PCR. The anti-proliferative activity of LINC00955 was evaluated using CRC cell lines in vitro and xenograft models in nude mice in vivo. The interaction of TRIM25-Sp1-DNMT3B-PHIP-CDK2 was analyzed by western blotting, protein degradation experiment, luciferase, RNA-IP, RNA pull-down assays and immunohistochemically analysis. The biological roles of LINC00955, tripartite motif containing 25 (TRIM25), Sp1 transcription factor (Sp1), DNA methyltransferase 3 beta (DNMT3B), pleckstrin homology domain interacting protein (PHIP), cyclin dependent kinase 2 (CDK2) in colorectal cancer cells were analyzed using ATP assays, Soft agar experiments and EdU assays. RESULTS: The present study showed that LINC00955 is downregulated in CRC tissues, and such downregulation is associated with poor prognosis of CRC patients. We found that LINC00955 can inhibit CRC cell growth both in vitro and in vivo. Evaluation of its mechanism of action showed that LINC00955 acts as a scaffold molecule that directly promotes the binding of TRIM25 to Sp1, and promotes ubiquitination and degradation of Sp1, thereby attenuating transcription and expression of DNMT3B. DNMT3B inhibition results in hypomethylation of the PHIP promoter, in turn increasing PHIP transcription and promoting ubiquitination and degradation of CDK2, ultimately leading to G0/G1 growth arrest and inhibition of CRC cell growth. CONCLUSIONS: These findings indicate that downregulation of LINC00955 in CRC cells promotes tumor growth through the TRIM25/Sp1/DNMT3B/PHIP/CDK2 regulatory axis, suggesting that LINC00955 may be a potential target for the therapy of CRC.

Microwave Three-Wave Mixing Spectroscopy of Chiral Molecules in Weakly Bound Complexes.

Since the first experimental implementation in 2013, microwave three-wave mixing has emerged as a robust spectroscopic approach for analyzing and controlling chiral molecules in the gas phase. This resonant, coherent, and nonlinear technique is based on the three-dimensional light-matter interaction in the electric dipole approximation, allowing for isomer- and conformer-selective chiral analysis with high resolution. Here we demonstrate the utility of microwave three-wave mixing for analyzing a molecular complex, limonene-H2O, which serves as a compelling example of addressing its potential to improve the chiral sensitivity for only weakly polar chiral molecules. The use of molecular complexes can also extend the applicability of microwave three-wave mixing to chiral systems that are not in the C1 point group.