Westlake University

Background Cytopathology cannot be used to reliably distinguish follicular thyroid adenoma (FTA) from follicular thyroid carcinoma (FTC), the second most common form of thyroid cancer, because they exhibit nearly identical cellular morphology. Given the challenges in diagnosis and treatment, this study aims to identify the mechanisms underlying FTC is essential. Methods Using parallel reaction monitoring-mass spectrometry (PRM-MS) assays, we identified and quantified 94 differentially expressed protein candidates from a retrospective cohort of 1085 FTC and FTA tissue samples from 18 clinical centers. Of these targeted proteins, those with the potential for distinguishing FTC from FTA were prioritized using machine learning. Co-immunoprecipitation (co-IP) and immunofluorescence co-localization assays, as well as gene interference, overexpression, and immunohistochemistry (IHC) experiments, were used to investigate the interactions and cellular functions of selected proteins. Results Using machine learning models and feature selection methods, 30 of the 94 candidates were prioritized as key proteins. Co-IP and immunofluorescence co-localization assays using FTC cell lines revealed interactions among insulin-like growth factor 2 receptor (IGF2R), major vault protei (MVP), histone deacetylase 1 (HDAC1), and histone H1.5 (H1-5). Gene interference and overexpression experiments in FTC-133 cells confirmed the promotional role of these proteins in cell proliferation. IHC assays of patient samples further confirmed elevated expression of these four proteins in FTC compared with that in FTA. Conclusions Our findings underscore the utility of advanced proteomic techniques in elucidating the molecular underpinnings of FTC, highlighting the potential significance of IGF2R, MVP, HDAC1, and H1-5 in FTC progression, and providing a foundation for the exploration of targeted therapies.

Ultrasonic spray pyrolysis enables scalable, multidimensional control of BiOI films, enhancing photoelectrochemical performance and facilitating bismuth-based material applications.

Background Antimicrobial resistance poses a substantial and growing threat to global health. While antibiotic resistance genes (ARGs) are tracked most closely in clinical settings, their spread remains poorly understood in non-clinical environments. Mitigating the spread of ARGs in non-clinical contexts such as soil could limit their enrichment in food webs. Results Multi-omics (involving metagenomics, metatranscriptomics, viromics, and metabolomics) and direct experimentation show that targeting keystone bacterial taxa by phages can limit ARG maintenance and dissemination in natural soil environments. Based on the metagenomic analysis, we first show that phages from activated sludge can regulate soil microbiome composition and function in terms of reducing ARG abundances and changing the bacterial community composition. This effect was mainly driven by a reduction in the abundance and activity of Streptomyces genus, which is well known for encoding both antibiotic resistance and synthesis genes. To validate the significance of this keystone species for the loss of ARGs, we enriched phage consortia specific to Streptomyces and tested their effect on ARG abundances on 48 soil samples collected across China. We observed a consistent reduction in ARG abundances across all soils, confirming that Streptomyces-enriched phages could predictably change the soil microbiome resistome and mitigate the prevalence of ARGs. This study highlights that phages can be used as ecosystem engineers to control the spread of antibiotic resistance in the environment. Conclusion Our study demonstrates that some bacterial keystone taxa are critical for ARG maintenance and dissemination in soil microbiomes, and opens new ecological avenues for microbiome modification and resistome control. This study advances our understanding of how metagenomics-informed phage consortia can be used to predictably regulate soil microbiome composition and functioning by targeting keystone bacterial taxa. 3cmU8RStwhfZ94ahX7b_G7Video Abstract

Background Gliomas represent the most prevalent primary neoplasm in the adult central nervous system. Despite advancements in therapeutic modalities, such as surgical intervention, radiotherapy, chemotherapy, and tumor treatment, the 5-year survival rate of glioma patients remains low. Therefore, there is an urgent need to develop additional treatment methods. Recent studies have suggested that FAM111B is involved in DNA repair, cell cycle regulation, and apoptosis. FAM111B mutations and overexpression are related to cancer. Methods We found that FAM111B was significantly overexpressed in glioma tissues compared to the adjacent tissues by analyzing data from the TCGA_GBM&LGG and CGGA databases. Moreover, overexpression of FAM111B was associated with shorter overall survival, and disease-specific survival and tended to increase with disease stage progression. Cellular experiments confirmed these results. These results suggest that overexpression of FAM111B promotes the proliferation, migration, and invasion of glioma cells, whereas the knockdown of FAM111B inhibits these activities. We also found that FAM111B regulated glioma cell proliferation, migration, and invasion via the PI3K/AKT pathway. Results FAM111B is capable of enhancing the proliferation, invasion, and migration capabilities of glioma cells and promotes the malignant progression of glioma via the PI3K/Akt signaling pathway. Conclusions This is the first study to demonstrate that FAM111B plays a crucial role in the proliferation, migration, and invasion of glioma cells. The malignant phenotype of FAM111B has also been shown to be closely associated with the PI3K/AKT pathway. FAM111B may be a predictive biomarker and a potential therapeutic target for gliomas.

We study the global solvability of the following chemotaxis system in an open bounded domain with smooth boundary $\Omega \subset \mathbb {R}^n$ with $n \ge 2$$\begin{aligned} {\left\{ \begin{array}{ll} u_t = \Delta (uv^{-\alpha })+ ru -\mu u^{\frac{n+2}{2}}\ln ^\gamma (u+e),\\ v_t = \Delta v -uv, \end{array}\right. } \end{aligned}$where $\alpha >0$, $r \in \mathbb {R}$, $\mu >0$, and $\gamma \ge 0$. In a recent paper [19], it was proven that $\gamma =0$, $\alpha \in (0,1)$ and n=2 can ensure the existence of global solutions with an additional smallness assumption for initial data $v_0$. In this paper, we show that the smallness assumption can be removed when n=2 and $\alpha \in (0,1]$. Moreover, we also demonstrate that solutions exist globally for any $\alpha > 0$ when $\gamma >\frac{(n-1)(n+2)}{2n}$ for any $n \ge 2$.

The hydrogen bonds (H‐bonds) between backbone amide and carbonyl groups are fundamental to the stability, structure, and dynamics of proteins. A key feature of such hydrogen bonding interactions is that multiple H‐bonds can enhance each other when aligned, as such in the ‐helix or ‐sheet secondary structures. To better understand this cooperative effect, we propose a new physical quantity to evaluate the cooperativity of intermolecular interactions. Using H‐bond aligned N‐methylacetamide molecules as the model system, we assess the cooperativity of protein backbone hydrogen bonds using quantum chemistry (QM) calculations at the MP2/aug‐cc‐pVTZ level, revealing cooperative energies ranging from 2 to 4.3 kcal/mol. A set of protein force fields was benchmarked against QM results. While the additive force field failed to reproduce cooperativity, polarizable force fields, including the Drude and AMOEBA protein force fields, have been found to reproduce the trend of QM results, albeit with smaller magnitude. This work demonstrates the theoretical utility of the proposed formula for quantifying cooperativity and its relevance in force field parameterization. Incorporating cooperative energy into polarizable models presents a pathway to achieving more accurate simulations of biomolecular systems.

Noble metal‐free electrodes for anion exchange membrane water electrolysis (AEM‐WE) operating at high current densities are critical for sustainable hydrogen production. However, the massive amount of bubbles resulted in insufficient mass transfer and unevenly distributed local stress, which poses a major challenge in designing an efficient and robust hydrogen evolution catalyst. Herein, a facile chemical corrosion method is developed to synthesize an interlayer‐anchored NiMo/MoO2 catalyst on a nickel foam (NF) substrate (NiMo/Int/NF) with high hydrogen evolution activity (overpotential of 80.2 ± 3.53 mV) and durability (stable for 5000 h) at 1000 mA cm⁻² in 1 m KOH. The interlayer tightly anchors the catalytic layer to the substrate, providing high compressive strength and strong adhesion to mitigate the bubble shock at a high current density. In situ Raman and X‐ray diffraction analyses reveal that the heterostructural catalytic layer can accelerate the hydrogen evolution reaction with increased local pH and high component utilization. Using NiMo/Int/NF as the cathode, the assembled noble metal‐free AEM‐WE device exhibits a low cell voltage of 1.78 V at 1000 mA cm⁻² (significantly lower than that of a Pt/C‐catalyzed cell (1.94 V)) while also showing excellent stability for 3000 h.

The preferred orientation phenomenon is a common issue in cryo-EM, posing a persistent challenge to conventional reconstruction methods. In this study, we introduce cryoPROS, a computational framework designed to correct misalignment caused by preferred orientation through co-refining the raw and auxiliary particles. These auxiliary particles, generated using a self-supervised deep generative model, enhance the alignment accuracy of particles in datasets affected by preferred orientation. CryoPROS achieved near-atomic resolution with the untilted HA-trimer dataset and successfully resolved high-resolution structures from three experimental datasets, including P001-Y, NaX, and hormone-sensitive lipase dimer, all affected by preferred orientation issues. Extensive experiments validate the robustness of cryoPROS and its minimal risk of introducing model bias. These findings suggest that in many cases thought to suffer from preferred orientation, addressing misalignment issues can lead to significant improvements in the density map.

Helminth infections, particularly in developing countries, remain a notable health burden worldwide. Group 3 innate lymphoid cells (ILC3s) are enriched in the intestine and play a critical role in immunity against extracellular bacteria and fungi. However, whether ILC3s are involved in intestinal helminth infection is still unclear. Here, we report that helminth infection reprograms ILC3s, which, in turn, promote anthelmintic immunity. ILC3-derived RANKL [receptor activator of NF-κB (nuclear factor κB) ligand] synergizes with interleukin-13 (IL-13) to facilitate intestinal tuft cell expansion after helminth infection, which further activates the tuft cell–group 2 innate lymphoid cell (ILC2) circuit to control helminth infection. Deletion of RANKL in ILC3s or deletion of RANK or its downstream adaptor RelB in intestinal epithelial cells substantially diminishes tuft cell hyperplasia and dampens anthelmintic immunity. Thus, ILC3s play an indispensable role in protecting against helminth infection through the regulation of intestinal tuft cell hyperplasia and type 2 immunity.

The development of new approaches to synthesize complex structures from readily available compounds is a topic of significant interest in synthetic chemistry. Herein, we present a straightforward strategy to access structurally intriguing arene-fused bicyclo[2.1.1]hexanes by a Lewis acid catalyzed annulation of phenol and their derivatives with bicyclo[1.1.0]butanes (BCBs). This reaction presumably proceeded through a cascade initiated by a dearomative (3+2) cycloaddition followed by rearomatization through alcohol or water elimination. The employment of hexafluoroisopropanol (HFIP) as solvent proved essential for facilitating this transformation. This methodology could accommodate a broad array of commercially available phenol derivatives including phenols and anisoles, thus allowing rapid generation of molecular complexity, which expands synthetic access to chemical space of bridged polycycles.

Allylic substitution reactions are essential in organic synthesis, enabling the transformation of allylic reagents into diverse alkenes. Traditional methods, which typically operate through ionic pathways, often require substrate preactivation to address high C─O bond dissociation energies, leading to challenges in regioselectivity and limited substrate compatibility. Here, we introduce an iron‐catalyzed radical pathway for allylic substitution that directly activates unprotected allylic alcohols, leveraging the redox and oxophilic properties of low‐valent iron to promote selective C─O bond cleavage and allylic transposition. This radical approach achieves high regio‐ and stereoselectivity, providing access to a broad array of di‐, tri‐, and tetra‐substituted alkenes with moderate to excellent yields and exceptional E/Z selectivity. Mechanistic studies confirm that the iron catalyst generates radical intermediates and mediates efficient dehydroxylation, enabling this direct transformation without protective groups or Lewis acid activators. The method's versatility is demonstrated through a broad substrate scope, including complex natural derivatives and functionalized alkyl halides, along with successful gram‐scale synthesis and downstream derivatization. This iron‐catalyzed radical pathway offers a sustainable and efficient alternative to conventional ionic methods, expanding the scope of allylic substitutions and advancing radical‐based methodologies in synthetic chemistry.

Renal ischemia‐reperfusion injury (RIRI) is a condition characterized by inflammation and cell damage in the kidneys following a period of ischemia and subsequent reperfusion, which lacks effective treating method in the clinic. Exploring molecular mechanisms holds profound significance in guiding the clinical prevention and treatment of RIRI. Herein, the potential function of Forkhead box C1 (FOXC1), a protein belongs to FOX family, in I/R‐induced injury in renal tubular epithelial cells (RTECs) was studied to explore potential targets for RIRI. FOXC1 was upregulated in RIRI rats, expressions of which were elevated as time prolonged. FOXC1‐overexpressed or knockdown HK‐2 cells were constructed, followed by I/R stimulation. FOXC1 was found markedly upregulated in I/R‐stimulated HK‐2 cells. Notably repressed cell viability, enhanced apoptosis, increased release of inflammatory cytokines, boosted reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and inactivated superoxide dismutase (SOD) enzyme were observed in I/R‐stimulated HK‐2 cells, which were sharply reversed by silencing FOXC1 and aggravated by overexpression FOXC1. Furthermore, largely increased levels of NLRP3, caspase‐1, GSDMD‐N, IL‐18, IL‐1β, and p‐p65/p65 were observed in I/R‐stimulated HK‐2 cells, which were notably suppressed by silencing FOXC1 and further elevated by overexpression FOXC1. Additionally, FOXC1‐overexpressed HK‐2 cells were stimulated by I/R with or without 10 μM MCC950, an inhibitor of NLRP3. The enhanced apoptosis, triggered inflammation, and facilitated ROS by FOXC1 overexpression in I/R‐stimulated HK‐2 cells were remarkably abolished by the coculture of MCC950, accompanied by an inhibition on the NF‐κB/NLRP3 signaling. Collectively, FOXC1 aggravated the I/R induced injury in RTECs by activating NF‐κB/NLRP3 signaling.

The oncogenic role and underlying mechanism of PRMT5 in pancreatic ductal adenocarcinoma (PAAD) remained to be elucidated. In this study, we aimed to investigate the oncogenic role, underlying molecular mechanisms, and potential therapeutic value of PRMT5 in PAAD. PRMT5 was significantly upregulated in pancreatic cancer than adjacent nontumor pancreas, which was positively correlated with poor prognosis. Genetic and pharmacological inhibition of PRMT5 suppressed PAAD proliferation in vitro and in vivo, exhibiting promising therapeutic effect in vivo. Mechanistically, PRMT5 directly bound to the promoter region of c‐Myc and activated its transcription. Transcriptionally activated c‐Myc in turn inhibited proteasome‐mediated degradation of PRMT5 and enhanced its protein stability, resulting in increased PRMT5 expression. The maintained PRMT5 further enhanced the transcription of c‐Myc. In conclusion, PRMT5 forms a positive feedback loop with c‐Myc to promote the proliferation of pancreatic cancer. Targeting this oncogenic communication may represent a novel and potential therapeutic approach for pancreatic cancer.

Organic molecules that serve as hole-selective contacts, known as self-assembled monolayers (SAMs), play a pivotal role in ensuring high-performance perovskite photovoltaics. Optimal energy alignment between the SAM and the perovskite is essential for desired photovoltaic performance. However, many SAMs are studied in optimal-bandgap perovskites, with limited energy level modification specifically catering to wide-bandgap perovskites. Herein, we demonstrate that the energy level of SAMs can be systematically tuned in a stepwise manner via inductive effects in the conjugated moieties, enabling rational design tailored for specific perovskite bandgaps. The resulting WBG perovskite device based on our tuned SAM achieved a power conversion efficiency (PCE) of 22.8%. Integration with crystalline silicon TOPCon subcells further enabled the construction of a perovskite/TOPCon tandem device with a PCE of 31.1% (certified 30.9%).

Octa-penta graphene (OPG), a novel carbon allotrope characterized by its distinctive arrangement of pentagonal and octagonal rings, has garnered considerable attention due to its exceptional structure and functional properties. This...

Most lung cancer (LC) patients are diagnosed at advanced stages due to the lack of effective screening tools. This multicenter study analyzes 1043 saliva samples (334 LC cases and 709 non‐LC cases) using a novel high‐throughput platform for metabolic fingerprint acquisition. Machine learning identifies 35 metabolic features distinguishing LC from non‐LC subjects, enabling the development of a classification model named SalivaMLD. In the validation set and test set, SalivaMLD demonstrates strong diagnostic performance, achieving an area under the curve of 0.849‐0.850, a sensitivity of 81.69–83.33%, and a specificity of 74.23–74.39%, outperforming conventional tumor biomarkers. Notably, SalivaMLD exhibits superior accuracy in distinguishing early stage LC patients. Hence, this rapid and noninvasive screening method may be widely applied in clinical practice for LC detection.