Distributed Privacy-Preserving Optimization With Accumulated Noise in ADMM.

Privacy preservation for distributed optimization in multiagent systems has been widely concerned in recent years. In this article, the accumulated noise privacy-preserving alternating direction method of multipliers (ANPPM) algorithm is proposed to preserve the private information of each agent. The masked states of each agent are sent to its neighbors with a designed noise-adding mechanism, and an accumulated term is introduced to confuse the gradients at each iteration. With ANPPM, all the agents can achieve privacy preservation for the information of real states and subgradients. Moreover, the states of all the agents can be guaranteed to converge to the optimal solution. The convergence rate of O(1/k) is consistent with standard ADMM, hence no adverse effect is induced by the privacy-preserving mechanism. Numerical results are provided to validate the effectiveness of the proposed ANPPM algorithm.

Mechanism and complex roles of HSC70/HSPA8 in viral entry.

The process of viruses entering host cells is complex, involving multiple aspects of the molecular organization of the cell membrane, viral proteins, the interaction of receptor molecules, and cellular signaling. Most viruses depend on endocytosis for uptake, when viruses reach the appropriate location, they are released from the vesicles, undergo uncoating, and release their genomes. Heat shock cognate protein 70(HSC70): also known as HSPA8, a protein involved in mediating clathrin-mediated endocytosis (CME), is involved in various viral entry processes. In this mini-review, our goal is to provide a summary of the function of HSC70 in viral entry. Understanding the interaction networks of HSC70 with viral proteins helps to provide new directions for targeted therapeutic strategies against viral infections.

Life's essential 8, genetic susceptibility, and incident cardiac arrhythmias: a population-based prospective cohort study.

BACKGROUND: Ideal cardiovascular health (CVH) has been associated with reduced cardiovascular disease risk and mortality, but its association with cardiac arrhythmias were still unsettled. In this prospective cohort study, we investigated the relationship between CVH and subsequent arrhythmias risk, including atrial fibrillation/flutter (AF), ventricular arrhythmias, and bradyarrhythmias. METHODS: Data from 287,264 participants initially free of arrhythmias in the UK Biobank were included in the analysis. Cox regression models were used to examine the relationship between CVH levels calculated by the American Heart Association's Life's Essential 8 (LE8) metrics, with cardiac arrhythmias risk. RESULTS: During a median follow-up period of 12.8 years, 16,802 incident AF, 2186 incident ventricular arrhythmias, and 4128 incident bradyarrhythmias were identified. After adjustment for confounding factors, participants with high initial CVH levels had a significantly lower risk for AF (HR 0.63, 95% CI 0.59-0.68), ventricular arrhythmias (HR 0.48, 95% CI 0.40-0.59), and bradyarrhythmias (HR 0.64, 95% CI 0.55-0.74) compared to those with low CVH levels. Furthermore, each SD increase in LE8 scores was associated with a 15% lower risk of AF, 21% for ventricular arrhythmias, and 13% for bradyarrhythmias, respectively. Additionally, a significant interaction was observed between CVH levels and the genetic risk of AF (P for interaction, 0.021). The reverse correlation seemed to be more noticeable in individuals with a lower genetic susceptibility to AF. CONCLUSIONS: We concluded that higher levels of CVH, estimated by the LE8 metrics, were associated with significantly reduced risks of AF, ventricular arrhythmias, and bradyarrhythmias.

Modulating Visible-Light Driven NIR Lanthanide Polymer Photocatalysis for Amplification Detection of Exosomal Proteins and Cancer Diagnosis.

Near-infrared (NIR) luminescent lanthanide materials hold great promise for bioanalysis, as they have anti-interference properties. The approach of efficient luminescence is sensitization through a reasonable chromophore to overcome the obstacle of the aqueous phase. The involvement of the surfactant motif is an innovative strategy to arrange the amphiphilic groups to be regularly distributed near the polymer to form a closed sensitized space. Herein, a lanthanide polymer (TCPP-PEI70K-FITC@Yb/SDBS) is designed in which the meso-tetra(4-carboxyphenyl)porphine (TCPP) ligand serves as both a sensitizer and photocatalytic switch. The surfactant sodium dodecyl benzenesulfonate (SDBS) wraps the photosensitive polymers to form a hydrophobic layer, which augments the light-harvesting ability and expedites its photocatalysis. TCPP-PEI70K-FITC@Yb/SDBS is subsequently applied as an amplified photocatalysis toolbox for universally regulating the generation of reactive oxygen species (ROS). Boosting 3,3',5,5'-tetramethylbenzidine (TMB) oxidation to produce blue products, a dual-mode biosensor is fabricated for improving the diagnosis of programmed death ligand-1-positive (PDL1) cancer exosomes. Exosomes were captured by Fe3O4 modified by the PDL1 aptamer, enabling replacement of alkaline phosphatase (ALP)-labeled multiple hybridized chains; then, the isolated ALP triggered a hydrolysis reaction to block the generation of oxTMB. Detection sensitivity improves by 1 order of magnitude through SDBS modulation, down to 104 particles/mL. The sensor performed well clinically in distinguishing cancer patients from healthy individuals, expanding physiological applications of near-infrared lanthanide luminescence.

TGF-ß1 mediates hypoxia-preconditioned olfactory mucosa mesenchymal stem cells improved neural functional recovery in Parkinson's disease models and patients.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN). Activation of the neuroinflammatory response has a pivotal role in PD. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for various nerve injuries, but there are limited reports on their use in PD and the underlying mechanisms remain unclear. METHODS: We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa (hOM)-MSCs on neural functional recovery in both PD models and patients, as well as the preventive effects on mouse models of PD. To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure, we employed single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) combined with full-length transcriptome isoform-sequencing (ISO-seq), and functional assay. Furthermore, we present the findings from an initial cohort of patients enrolled in a phase I first-in-human clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients. RESULTS: A functional assay identified that transforming growth factor-ß1 (TGF-ß1), secreted from hOM-MSCs, played a critical role in modulating mitochondrial function recovery in dopaminergic neurons. This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN, which are closely associated with neuroinflammatory responses. Mechanistically, exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-ß1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B (ALK/PI3K/Akt) signaling pathway in microglia located in the SN of PD patients. Furthermore, intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD. CONCLUSIONS: These findings provide compelling evidence for the involvement of TGF-ß1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD. Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD. Additionally, TGF-ß1 may be used alone or combined with hOM-MSCs therapy for treating PD.

Extended Left Hemihapatectomy with Right Hepatic Artery Reconstruction for Primary Hepatic Neuroendocrine Neoplasm: A Brief Report.

BACKGROUND rimary hepatic neuroendocrine neoplasms (PHNEN) are exceedingly rare tumors with atypical clinical manifestations, accounting for less than 0.5% of all neuroendocrine tumors. Currently, there is a lack of consensus on their management, and guidelines do not recommend postoperative chemotherapy for patients with stage G1/G2 disease after curative resection. We present a case report of PHNEN, outlining its diagnostic challenges, treatment strategy, and clinical outcomes. CASE REPORT A 31-year-old man presented with jaundice and was initially diagnosed with suspected IgG4-related disease, which initially appeared to respond to steroid therapy, but manifested worsening jaundice 4 months after initial treatment. Subsequent evaluation revealed a PHNEN NET G2 with lymph node metastasis and invasion of the right hepatic artery; and involvement of the hepatic duct at the hepatic hilum, primarily the left hepatic duct. The patient underwent extended left hemi-hepatectomy with caudate lobe resection, bile duct resection, and lymphadenectomy, followed by reconstruction of the right hepatic artery. Postoperatively, the patient received adjuvant chemotherapy consisting of capecitabine (1000 mg bid D1-14) and temozolomide (200 mg qn D10-14) for 6 cycles. Currently, the patient remains disease free 43 months after treatment. CONCLUSIONS PHNEN presents diagnostic challenges due to its rarity and lack of specific markers. Surgical resection remains the cornerstone of treatment, with chemotherapy being considered in select cases with high-risk features. Further research is needed to refine treatment approaches and improve outcomes for patients with PHNEN.

Organic Passivation-Enhanced Ferroelectricity in Perovskite Oxide Films.

Perovskite oxides and organic-inorganic halide perovskite materials, with numerous fascinating features, have been subjected to extensive studies. Most of the properties of perovskite materials are dependence on their ferroelectricity that denoted by remanent polarization (Pr). Thus, the increase of Pr in perovskite films is mainly an effort in material physics. At present, commonplace improvement schemes, i.e., controlling material crystallinity, and post-annealing by using a high-temperature process, are normally used. However, a simpler and temporal strategy for Pr improvement is always unavailable to perovskite material researchers. In this study, an organic coating layer, low-temperature, and vacuum-free strategy is proposed to improve the Pr, directly increasing the Pr from 36 to 56 µC cm-2. Further study finds that the increased Pr originates from the suppression of the oxygen defects and Ti defects. This organic coating layer strategy for passivating the defects may open a new way for the preparation of higher-performance and cost-effective perovskite products, further improving its prospective for application in the electron devices field.

Individualized Structural Perturbations on Normative Brain Connectome Restrict Deep Brain Stimulation Outcomes in Parkinson's Disease.

BACKGROUND: Patients with Parkinson's disease (PD) respond to deep brain stimulation (DBS) variably. However, how brain substrates restrict DBS outcomes remains unclear. OBJECTIVE: In this article, we aim to identify prognostic brain signatures for explaining the response variability. METHODS: We retrospectively investigated a cohort of patients with PD (n = 141) between 2017 and 2022, and defined DBS outcomes as the improvement ratio of clinical motor scores. We used a deviation index to quantify individual perturbations on a reference structural covariance network acquired with preoperative T1-weighted magnetic resonance imaging. The neurobiological perturbations of patients were represented as z scored indices based on the chronological perturbations measured on a group of normal aging adults. RESULTS: After applying stringent statistical tests (z > 2.5) and correcting for false discoveries (P < 0.01), we found that accelerated deviations mainly affected the prefrontal cortex, motor strip, limbic system, and cerebellum in PD. Particularly, a negative network within the accelerated deviations, expressed as "more preoperative deviations, less postoperative improvements," could predict DBS outcomes (mean absolute error = 0.09, R2 = 0.15). Moreover, a fusion of personal brain predictors and medical responses significantly improved traditional evaluations of DBS outcomes. Notably, the most important brain predictor, a pathway connecting the cognitive unit (prefrontal cortex) and motor control unit (cerebellum and motor strip), partially mediates DBS outcomes with the age at surgery. CONCLUSIONS: Our findings suggest that individual structural perturbations on the cognitive motor control circuit are critical for modulating DBS outcomes. Interventions toward the circuit have the potential for additional clinical improvements. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.

The DNA-dependent protein kinase (DNA-PK), catalytic subunit, also known as DNA-PKcs, is complexed with the heterodimer Ku70/Ku80 to form DNA-PK holoenzyme, which is well recognized as initiator in the nonhomologous end joining (NHEJ) repair after double strand break (DSB). During NHEJ, DNA-PKcs is essential for both DNA end processing and end joining. Besides its classical function in DSB repair, DNA-PKcs also shows multifaceted functions in various biological activities such as class switch recombination (CSR) and variable (V) diversity (D) joining (J) recombination in B/T lymphocytes development, innate immunity through cGAS-STING pathway, transcription, alternative splicing, and so on, which are dependent on its function in NHEJ or not. Moreover, DNA-PKcs deficiency has been proven to be related with human diseases such as neurological pathogenesis, cancer, immunological disorder, and so on through different mechanisms. Therefore, it is imperative to summarize the latest findings about DNA-PKcs and diseases for better targeting DNA-PKcs, which have shown efficacy in cancer treatment in preclinical models. Here, we discuss the multifaceted roles of DNA-PKcs in human diseases, meanwhile, we discuss the progresses of DNA-PKcs inhibitors and their potential in clinical trials. The most updated review about DNA-PKcs will hopefully provide insights and ideas to understand DNA-PKcs associated diseases.

Dynamic causal modeling analysis reveals the modulation of motor cortex and integration in superior temporal gyrus during multisensory speech perception.

The processing of speech information from various sensory modalities is crucial for human communication. Both left posterior superior temporal gyrus (pSTG) and motor cortex importantly involve in the multisensory speech perception. However, the dynamic integration of primary sensory regions to pSTG and the motor cortex remain unclear. Here, we implemented a behavioral experiment of classical McGurk effect paradigm and acquired the task functional magnetic resonance imaging (fMRI) data during synchronized audiovisual syllabic perception from 63 normal adults. We conducted dynamic causal modeling (DCM) analysis to explore the cross-modal interactions among the left pSTG, left precentral gyrus (PrG), left middle superior temporal gyrus (mSTG), and left fusiform gyrus (FuG). Bayesian model selection favored a winning model that included modulations of connections to PrG (mSTG → PrG, FuG → PrG), from PrG (PrG → mSTG, PrG → FuG), and to pSTG (mSTG → pSTG, FuG → pSTG). Moreover, the coupling strength of the above connections correlated with behavioral McGurk susceptibility. In addition, significant differences were found in the coupling strength of these connections between strong and weak McGurk perceivers. Strong perceivers modulated less inhibitory visual influence, allowed less excitatory auditory information flowing into PrG, but integrated more audiovisual information in pSTG. Taken together, our findings show that the PrG and pSTG interact dynamically with primary cortices during audiovisual speech, and support the motor cortex plays a specifically functional role in modulating the gain and salience between auditory and visual modalities. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09945-z.

Recent advances in circularly polarized luminescence of planar chiral organic compounds.

Circularly polarized luminescence (CPL), as an important chiroptical phenomenon, can not only directly characterize excited-state structural information about chiroptical materials but also has great application prospects in 3D optical displays, information storage, biological probes, CPL lasers and so forth. Recently, chiral organic small molecules with CPL have attracted a lot of research interest because of their excellent luminescence efficiency, clear molecular structures, unique flexibility and easy functionalization. Planar chiral organic compounds make up an important class of chiral organic small molecular materials and often have rigid macrocyclic skeletons, which have important research value in the field of chiral supramolecular chemistry (e.g., chiral self-assembly and chiral host-guest chemistry). Therefore, research into planar chiral organic compounds has become a hotspot for CPL. It is time to summarize the recent developments in CPL-active compounds based on planar chirality. In this feature article, we summarize various types of CPL-active compounds based on planar chirality. Meanwhile, we overview recent research in the field of planar chiral CPL-active compounds in terms of optoelectronic devices, asymmetric catalysis, and chiroptical sensing. Finally, we discuss their future research prospects in the field of CPL-active materials. We hope that this review will be helpful to research work related to planar chiral luminescent materials and promote the development of chiral macrocyclic chemistry.

The first-principles study of interfacial bonding strength and segregation behavior of alloyed elements at the η(MgZn2)/Al interface.

For precipitation-strengthened Al alloys, the interfacial segregation behavior of alloying elements plays an important role in controlling the effectiveness of precipitation strengthening. In this work, the adhesion work (Wad) and interfacial energy (γ) of the η(0001)/Al(111) interface were studied to gain an insight into the interface properties between the precipitate η and the Al matrix. Additionally, we examined the impact of the segregation behavior of alloyed elements on the bonding strength of the interface. The computed values for Wad and interfacial energies indicated that the T6S3 terminated configuration represents the interfacial structure with the highest stability across all models analyzed. Focusing on the T6S3 interface, the assessed segregated energies (Eseg) disclose that the segregation ability of elements from strong to weak exhibits the order of Ti > Sc > Zr > Y > Ta > Nb > Lu > Hf > Mo > V > W, while Cr and Mn elements are not easy to segregate at the interface. Sc, Ti, V, Cr, Mn, Zr, Nb, Mo, Hf, and Ta preferentially occupy Al atoms, whereas Y and Lu predominantly inhabit Mg atoms. Relative to the clean interface, the electron cloud enrichment at the interface after alloying element X (Zr, Sc, Ti, W, Hf, Mn, Y, Lu and V) doping is weakened, and the ion interaction among interface atoms is enhanced. After doping alloying element X (Nb, Mo, Ta, and Cr), the degree of electron cloud enrichment at the interface is obviously enhanced, and the covalent interaction among interface atoms is enhanced. This suggests that the introduction of alloyed elements through doping can augment the bond strength at the interface between the precipitated phase and matrix, thereby reinforcing the strength and toughness of 7xxx series alloys.

Effects of melatonin on sperm quality, enzyme activity, antioxidant gene expression and fertility of cryopreserved bovine semen.

Melatonin (MLT) has strong antioxidant capacity and can reduce the damage caused by oxidative stress in sperm, but there is still little content in the field we have studied. In this study, we are committed to scientific research on adding melatonin to Belgian blue bull semen diluent for cryopreservation. Different concentrations (0, 0.1, 0.3, 0.5 or 0.7 mg/mL) of MLT were added diluent. Sperm kinetic parameters, enzyme activity, antioxidant gene expression and fertility were analyzed after thawing. The results showed that MLT concentration of 0.3 mg/mL exerted positive effects on post-thaw kinetic parameters. Compared with other groups, 0.3 mg/mL MLT treated sperm acrosome and plasma membrane integrity, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels significantly increased. Meanwhile, the mRNA expression of antioxidant genes SOD2, CAT and GPx increased in the 0.3 mg/mL MLT treatment group, and the mRNA expression of apoptosis genes Caspase-3 and Bax were significantly reduced. In addition, in vitro fertilization (IVF) embryo cleavage, blastocyst rate and artificial insemination (AI) pregnancy rate were higher in 0.3 mg/mL MLT. Therefore, MLT showed cryoprotective capacity to the freezing diluent used for Belgian blue bull sperm during the process of freezing-thawing, and the optimal concentration of MLT for the frozen diluent was 0.3 mg/mL.

Cryptic diversity and rampant hybridization in annual gentians on the Qinghai-Tibet Plateau revealed by population genomic analysis.

Understanding the evolutionary and ecological processes involved in population differentiation and speciation provides critical insights into biodiversity formation. In this study, we employed 29,865 single nucleotide polymorphisms (SNPs) and complete plastomes to examine genomic divergence and hybridization in Gentiana aristata, which is endemic to the Qinghai-Tibet Plateau (QTP) region. Genetic clustering revealed that G. aristata is characterized by geographic genetic structures with five clusters (West, East, Central, South and North). The West cluster has a specific morphological character (i.e., blue corolla) and higher values of FST compared to the remaining clusters, likely the result of the geological barrier formed by the Yangtze River. The West cluster diverged from the other clusters in the Early Pliocene; these remaining clusters diverged from one another in the Early Quaternary. Phylogenetic reconstructions based on SNPs and plastid data revealed substantial cyto-nuclear conflicts. Genetic clustering and D-statistics demonstrated rampant hybridization between the Central and North clusters, along the Bayankala Mountains, which form the geological barrier between the Central and North clusters. Species distribution modeling demonstrated the range of G. aristata expanded since the Last Interglacial period. Our findings provide genetic and morphological evidence of cryptic diversity in G. aristata, and identified rampant hybridization between genetic clusters along a geological barrier. These findings suggest that geological barriers and climatic fluctuations have an important role in triggering diversification as well as hybridization, indicating that cryptic diversity and hybridization are essential factors in biodiversity formation within the QTP region.

In Situ Synthesis of Liquid Metal Conductive Fibers toward Smart Cloth.

To meet the diverse needs of humans, smart cloth has become a potential research hotspot to replace traditional cloth. However, it is challenging to manufacture a flexible fabric with multiple functions. Here, we introduce a smart cloth based on liquid metal (LM) conductive fibers. Ga2O3 nanoparticles are obtained through ultrasonic pretreatment. Furthermore, a coordination bond is formed between thiol groups on the surface of protein fibers and Ga2O3 through a scraping method, allowing Ga2O3 particles to be grafted onto the surface of protein fibers in situ. Finally, LM conductive fibers are encapsulated using a photocuring adhesive. In addition, a wearable smart cloth integrated with multiple sensors has been developed based on LM conductive fibers. Users can not only monitor their movement trajectory and the surrounding environment in real time but also have their data supervised by family members through a client, achieving remote and continuous monitoring. The development of this wearable smart cloth provides strong support for future wearable, flexible electronic devices.

Astragaloside IV ameliorates indomethacin-induced intestinal inflammation in rats through inhibiting the activation of NLRP3 inflammasome.

The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) may cause significant intestinal alteration and inflammation and lead to the occurrence of inflammatory diseases resembling duodenal ulcers. Astragaloside IV (AS-IV) is a glycoside of cycloartane-type triterpene isolated from the dried root of Astragalus membranaceus (Fisch.) Bge. (family Fabaceae), and has been used for ameliorating the NSAID-induced inflammation in the small intestine. The present study aimed to investigate the effects of AS-IV on indomethacin (IND)-induced inflammation in the small intestine of rats and its underlying mechanisms. Hematoxylin-eosin (H&E) staining, transmission and scanning electron microscopy were carried out to observe the surface morphology and ultrastructure of the small intestinal mucosa. Immunofluorescence and ELISA tests were employed to detect the expressions of NLRP3, ASC, caspase-1, and NF-κB proteins, as well as inflammatory factors IL-1ß and IL-18, to uncover potential molecular mechanisms responsible for mitigating small intestinal inflammation. The results demonstrated that AS-IV significantly decreased the ulcer index, improved the surface morphology and microstructure of the small intestinal mucosa, and increased mucosal blood flow. Molecular docking revealed a strong and stable binding capacity of AS-IV to NLRP3, ASC, caspase-1, and NF-κB proteins. Further experimental validation exhibited that AS-IV markedly decreased levels of IL-1ß and IL-18, and inhibited the protein expression of NLRP3, ASC, caspase-1, and NF-κB. Our data demonstrate that AS-IV ameliorates IND-induced intestinal inflammation in rats by inhibiting the activation of NLRP3 inflammasome and reducing the release of IL-1ß and IL-18, thereby representing a promising therapy for IND-induced intestinal inflammation.

Hypoxia inhibits ferritinophagy-mediated ferroptosis in esophageal squamous cell carcinoma via the USP2-NCOA4 axis.

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy of the digestive system. Hypoxia is a crucial player in tumor ferroptosis resistance. However, the molecular mechanism of hypoxia-mediated ferroptosis resistance in ESCC remains unclear. Here, USP2 expression was decreased in ESCC cell lines subjected to hypoxia treatment and was lowly expressed in clinical ESCC specimens. Ubiquitin-specific protease 2 (USP2) depletion facilitated cell growth, which was blocked in USP2-overexpressing cells. Moreover, USP2 silencing enhanced the iron ion concentration and lipid peroxidation accumulation as well as suppressed ferroptosis, while upregulating USP2 promoted ferroptotic cell death in ESCC cells. Furthermore, knockout of USP2 in ESCC models discloses the essential role of USP2 in promoting ESCC tumorigenesis and inhibiting ferroptosis. In contrast, overexpression of USP2 contributes to antitumor effect and ferroptosis events in vivo. Specifically, USP2 stably bound to and suppressed the degradation of nuclear receptor coactivator 4 (NCOA4) by eliminating the Lys48-linked chain, which in turn triggered ferritinophagy and ferroptosis in ESCC cells. Our findings suggest that USP2 plays a crucial role in iron metabolism and ferroptosis and that the USP2/NCOA4 axis is a promising therapeutic target for the management of ESCC.

Analysis of Body Mass Index and Clinicopathological Factors in Patients with Papillary Thyroid Carcinoma.

Objective: To analyze the correlation between body mass index (BMI) and clinicopathological factors of papillary thyroid cancer (PTC). Methods: The clinical data of patients with PCT who were hospitalized in the Department of Thyroid Surgery of the Affiliated Hospital of Guizhou Medical University from March 2023 to September 2023 were retrospectively collected, including age, gender, height, weight, BMI, v-raf murine sarcoma viral oncogene homolog B (BRAF) gene mutation, tumor size, multifocus, Hashimoto's thyroiditis, lymph node metastasis and other clinicopathological factors. According to the World Health Organization (WHO) definition for Asian population, BMI≥25kg/m2 was obese group, 23≤BMI≤24.9kg/m2 was overweight group, 18.5≤BMI≤22.9kg/m2 was normal weight group, and BMI≤18.5kg/m2 was low weight group. The clinicopathological factors of overweight and obese patients with PTC were analyzed. Results: A total of 164 PTC patients were included, with an average BMI of (24.44±3.57) kg/m2. Age of overweight and obese PTC patients (Z=1.978, p=0.083); Gender of overweight and obese PTC patients (χ2 value: 11.570, p=0.004); Tumor size in overweight and obese PTC patients (Z=0.894, p=0.411); BRAF gene mutation in overweight and obese PTC patients (χ2 value: 1.452, p =0.623); Multifocal lesions were found in overweight and obese patients (χ2 value: 1.653, p =0.201). Hashimoto's thyroiditis was found in overweight and obese PTC patients (χ2 value: 1.147, p=0.298). Overweight and obese patients with PTC had lymph node metastasis (χ2 value: 1.690, p =0.251). Conclusion: Overweight and obesity in PTC patients are correlated with male, but not with age, tumor size, BRAF mutation, multifocality, Hashimoto's thyroiditis and lymph node metastasis.

ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironment.

BACKGROUND: The hypoxic tumor microenvironment is a key factor that promotes metabolic reprogramming and vascular mimicry (VM) in ovarian cancer (OC) patients. ESM1, a secreted protein, plays an important role in promoting proliferation and angiogenesis in OC. However, the role of ESM1 in metabolic reprogramming and VM in the hypoxic microenvironment in OC patients has not been determined. METHODS: Liquid chromatography coupled with tandem MS was used to analyze CAOV3 and OV90 cells. Interactions between ESM1, PKM2, UBA2, and SUMO1 were detected by GST pull-down, Co-IP, and molecular docking. The effects of the ESM1-PKM2 axis on cell glucose metabolism were analyzed based on an ECAR experiment. The biological effects of the signaling axis on OC cells were detected by tubule formation, transwell assay, RT‒PCR, Western blot, immunofluorescence, and in vivo xenograft tumor experiments. RESULTS: Our findings demonstrated that hypoxia induces the upregulation of ESM1 expression through the transcription of HIF-1α. ESM1 serves as a crucial mediator of the interaction between PKM2 and UBA2, facilitating the SUMOylation of PKM2 and the subsequent formation of PKM2 dimers. This process promotes the Warburg effect and facilitates the nuclear translocation of PKM2, ultimately leading to the phosphorylation of STAT3. These molecular events contribute to the promotion of ovarian cancer glycolysis and vasculogenic mimicry. Furthermore, our study revealed that Shikonin effectively inhibits the molecular interaction between ESM1 and PKM2, consequently preventing the formation of PKM2 dimers and thereby inhibiting ovarian cancer glycolysis, fatty acid synthesis and vasculogenic mimicry. CONCLUSION: Our findings demonstrated that hypoxia increases ESM1 expression through the transcriptional regulation of HIF-1α to induce dimerization via PKM2 SUMOylation, which promotes the OC Warburg effect and VM.