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Abstract Glioblastoma multiforme (GBM) is the most therapeutically challenging primary brain tumor owing to the unique physiological structure of the blood–brain barrier. Lately, research on targeted therapy for gliomas has shifted focus toward the tumor microenvironment and local immune responses. Pyroptosis is a newly identified cellular demise characterized by the release of numerous inflammatory factors. While pyroptosis shows promise in impeding the occurrence and progression of GBM, the regulatory mechanisms governing this process in gliomas still require further investigation. The function of the Enhancer of zeste homolog 2 (EZH2) in pyroptosis remains unexplored. In this study, we discovered that 3-Deazaneplanocin A (DZNep), an inhibitor of EZH2, can induce pyroptosis in GBM in vitro experiments. Moreover, our investigation unveiled that the signal transducer and activator of transcription (STAT3) could serve as a downstream regulator influenced by EZH2, impacting pyroptosis in GBM. Following treatment with DZNep and the STAT3 inhibitor (SH-4–54), there was an elevation in the levels of pyroptosis-related factors, namely NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) and Gasdermin D (GSDMD). Moreover, simultaneous inhibition of both EZH2 and STAT3 led to the expression of inflammatory factors such as IL-1β and IL-18. In summary, we have identified that EZH2 regulates pyroptosis in GBM through STAT3, and pyroptosis could potentially be targeted for immunotherapy in GBM.

Abstract Previous research has produced inconsistent findings concerning the connection between metabolic syndrome and prostate cancer. It is challenging for observational studies to establish a conclusive causal relationship between the two. However, Mendelian randomization can provide stronger evidence of causality in this context. To examine the causal link between a metabolic composite and its components with prostate cancer, we performed a two-sample Mendelian randomization (MR) study utilizing aggregated data from genome-wide association studies, followed by meta-analyses. In our study, we employed inverse variance weighting as the primary method for MR analysis. Additionally, we assessed potential sources of heterogeneity and horizontal pleiotropy through the Cochran’s Q test and MR-Egger regression. Moreover, we used multivariate MR to determine whether smoking versus alcohol consumption had an effect on the outcomes. We found no causal relationship between metabolic syndrome and its components and prostate cancer(MetS, odds ratio [OR] = 0.95, 95% confidence interval [CI] = 0.738–1.223, p = 0.691; TG, [OR] = 1.02, 95%[CI] = 0.96–1.08, p = 0.59); HDL, [OR] = 1.02, 95% [CI] = 0.97–1.07, p = 0.47; DBP, [OR] = 1.00, 95%[CI] = 0.99–1.01, p = 0.87; SBP, [OR] = 1.00, 95%[CI] = 0.99–1.00, p = 0.26; FBG [OR] = 0.92, 95%[CI] = 0.81–1.05, p = 0.23; WC, [OR] = 0.93, 95%[CI] = 0.84–1.03, p = 0.16). Finally, the MVMR confirms that the metabolic syndrome and its components are independent of smoking and alcohol consumption in prostate cancer. We didn’t find significant evidence to determine a causal relationship between the metabolic syndrome and its components and prostate cancer through MR analysis. Further research is necessary to explore the potential pathogenesis between the two diseases.

Abstract Objective This cross‐sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID‐19 in China. Methods This study was conducted by 45 tertiary Grade‐A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID‐19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self‐reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions The incidence of dysosmia and dysgeusia following infection with the SARS‐CoV‐2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS‐CoV‐2 vaccination, history of head‐facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

Abstract Major depressive disorder (MDD) is characterized by psychomotor retardation whose underlying neural source remains unclear. Psychomotor retardation may either be related to a motor source like the motor cortex or, alternatively, to a psychomotor source with neural changes outside motor regions, like input regions such as visual cortex. These two alternative hypotheses in main (n = 41) and replication (n = 18) MDD samples using 7 Tesla MRI are investigated. Analyzing both global and local connectivity in primary motor cortex (BA4), motor network and middle temporal visual cortex complex (MT+), the main findings in MDD are: 1) Reduced local and global synchronization and increased local‐to‐global output in motor regions, which do not correlate with psychomotor retardation, though. 2) Reduced local‐to‐local BA4 – MT+ functional connectivity (FC) which correlates with psychomotor retardation. 3) Reduced global synchronization and increased local‐to‐global output in MT+ which relate to psychomotor retardation. 4) Reduced variability in the psychophysical measures of MT+ based motion perception which relates to psychomotor retardation. Together, it is shown that visual cortex MT+ and its relation to motor cortex play a key role in mediating psychomotor retardation. This supports psychomotor over motor hypothesis about the neural source of psychomotor retardation in MDD.

Abstract Chronic pancreatitis (CP) is a complex disease with genetic and environmental factors at play. Through trio exome sequencing, a de novo SEC16A frameshift variant in a Chinese teenage CP patient is identified. Subsequent targeted next‐generation sequencing of the SEC16A gene in 1,061 Chinese CP patients and 1,196 controls reveals a higher allele frequency of rare nonsynonymous SEC16A variants in patients (4.90% vs 2.93%; odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26–2.33). Similar enrichments are noted in a French cohort (OR, 2.74; 95% CI, 1.67–4.50) and in a biobank meta‐analysis (OR, 1.16; 95% CI, 1.04–1.31). Notably, Chinese CP patients with SEC16A variants exhibit a median onset age 5 years earlier than those without (40.0 vs 45.0; p = 0.012). Functional studies using three CRISPR/Cas9‐edited HEK293T cell lines show that loss‐of‐function SEC16A variants disrupt coat protein complex II (COPII) formation, impede secretory protein vesicles trafficking, and induce endoplasmic reticulum (ER) stress due to protein overload. Sec16a+/− mice, which demonstrate impaired zymogen secretion and exacerbated ER stress compared to Sec16a+/+, are further generated. In cerulein‐stimulated pancreatitis models, Sec16a+/− mice display heightened pancreatic inflammation and fibrosis compared to wild‐type mice. These findings implicate a novel pathogenic mechanism predisposing to CP.

The prevailing opinion emphasizes fronto-parietal network (FPN) is key in mediating general fluid intelligence (gF). Meanwhile, recent studies show that human MT complex (hMT+), located at the occipito-temporal border and involved in 3D perception processing, also plays a key role in gF. However, the underlying mechanism is not clear, yet. To investigate this issue, our study targets visuo-spatial intelligence, which is considered to have high loading on gF. We use ultra-high field magnetic resonance spectroscopy (MRS) to measure GABA/Glu concentrations in hMT+ combining resting-state fMRI functional connectivity (FC), behavioral examinations including hMT+ perception suppression test and gF subtest in visuo-spatial component. Our findings show that both GABA in hMT+ and frontal-hMT+ functional connectivity significantly correlate with the performance of visuo-spatial intelligence. Further, serial mediation model demonstrates that the effect of hMT+ GABA on visuo-spatial gF is fully mediated by the hMT+ frontal FC. Together our findings highlight the importance in integrating sensory and frontal cortices in mediating the visuo-spatial component of general fluid intelligence.

BackgroundHigh altitude pulmonary edema (HAPE) is an idiopathic, noncardiogenic form of pulmonary edema that occurs at high altitudes. It is characterized by a severe clinical course and carries a significant mortality risk. Despite its clinical relevance, the molecular mechanisms underlying HAPE are not well understood.MethodsWe conducted whole-transcriptome RNA sequencing on blood samples from 6 pairs of HAPE patients and healthy controls to identify differentially expressed (DE) mRNAs, miRNAs, circRNAs, lncRNAs, along with alternative splicing (AS) events, gene fusions, and novel transcripts. To explore the regulatory dynamics, we constructed ceRNA networks and analyzed immune cell infiltration patterns, further annotating the biological functions of these transcripts. For empirical validation, we selected five circRNAs from the ceRNA network and conducted RT-qPCR on 50 paired samples. Additionally, we assessed the correlations between circRNA expression levels and clinical data to evaluate their diagnostic potential.ResultsWe observed 2,023 differentially expressed mRNAs (DEmRNAs), 84 DEmiRNAs, 200 DEcircRNAs, and 3,573 DElncRNAs. A total of 139 ‘A3SS’ events, 103 ‘A5SS’ events, 545 ‘MXE’ events, 14 ‘RI’ events, and 1,482 ‘SE’ events were identified in the AS events analysis between the two groups. Two ceRNA networks were constructed. T cells, follicular helper, and Macrophages M1 cells exhibited the strongest positive correlation (R=0.82), while naive B cells and memory B cells demonstrated the strongest negative correlation (R=-0.62). In total, the expression of three circRNAs was significantly different in a larger cohort. Hsa_circ_0058497, hsa_circ_0081006, and hsa_circ_0083220 demonstrated consistent with the RNA sequencing results. These three circRNAs strongly correlate with clinical indicators and exhibit potential as diagnostic biomarkers. Finally, we verified five genes (CXCR4, HSD17B2, ANGPTL4, TIMP3, N4BP3) that were differentially expressed in endothelial cells under normoxia and hypoxia through bioinformatics and RT-qPCR analyses.ConclusionThis study elucidates the differential expression of coding and non-coding RNAs (ncRNAs) in HAPE, identifies new transcripts and genes, and enhances our understanding of the transcriptional characteristics of HAPE. Moreover, it highlights the potential role of circRNAs in advancing the diagnosis and treatment of HAPE.

In this study, we report for the first time a new gabbro diorite, forming in an intraplate extensional environment during the Early Devonian, in the Shimian of the western margin of the Yangtze Block. Zircon SIMS U–Pb dating indicates that the gabbro diorite formed at ca. 406 Ma. This gabbro diorite belongs to low-K tholeiite and has enriched in Rb, Ba, K, Pb, negative anomalies of Nb, Ta, depletion of flat LREE patterns, negative εHf(t) (−1.1 to −11.7), and high δ18O (8.83 ± 0.21‰) ratios, showing that the magma formed by partial melting of N-MROB-type mantle and indicating that the magma underwent crustal contamination during emplacement. The magma is formed in the extensional environment, which provides evidence for the extensional environment in the western margin of the Yangtze. The geochemical characteristics and emplacement time of the rocks are similar to those in the early Paleozoic post-orogenic mafic rocks in South China, suggesting that the gabbro diorite may be influenced by the early Paleozoic orogeny in South China.

The generation of cold molecules is an important topic in the field of cold atoms and molecules and has received relevant advanced research attention in ultracold chemistry, quantum computation, and quantum metrology. With a high atomic phase space density, optical dipole traps have been widely used to prepare, trap, and study cold molecules. In this work, Rb2 molecules were photoassociated in a magneto-optical trap to obtain a precise rovibrational spectrum, which provided accurate numerical references for the realization of multiple frequency photoassociation. By meeting the harsh requirements of photoassociation in optical dipole traps, the cold molecule photoassociation process was well explored, and different photoassociation resonances were simultaneously addressed in a single optical dipole trap. This method can be universally extended to simultaneously photoassociate cold molecules with different internal states or atomic species in a single optical dipole trap, thus advancing generous cold molecule studies such as cold molecule collision dynamics. [ABSTRACT FROM AUTHOR]

Approximately 20% of colorectal cancer (CRC) patients are first diagnosed with metastatic colorectal cancer (mCRC) because they develop symptoms at an advanced stage. Despite advancements in treatment, patients with metastatic disease still experience inferior survival rates. Our objective is to investigate the association between long noncoding RNAs (lncRNAs) and prognosis and to explore their role in mCRC. In this study, we find that elevated expression of PCAT6 is independently linked to unfavourable survival outcomes in The Cancer Genome Atlas (TCGA) data, and this finding is further confirmed in CRC samples obtained from Fudan University Shanghai Cancer Center. Cell lines and xenograft mouse models are used to examine the impact of PCAT6 on tumor metastasis. Knockdown of PCAT6 is observed to impede the metastatic phenotype of CRC, as evidenced by functional assays, demonstrating the suppression of epithelial-mesenchymal transition (EMT) and stemness. Our findings show the significance of PCAT6 in mCRC and its potential use as a prognostic biomarker.

Let GRS$ _k(\boldsymbol{\alpha}, \boldsymbol{\upsilon}) $ be a $ k $-dimensional generalized Reed-Solomon (GRS) code over $ \mathbb{F}_q $ associated with $ \boldsymbol{\alpha} = (\alpha_1, \ldots, \alpha_n) $ and $ \boldsymbol{\upsilon} = (\upsilon_1, \ldots, \upsilon_n) $. In this paper, we determined the dimension of the Euclidean hull GRS$ _k(\boldsymbol{\alpha}, \boldsymbol{\upsilon})\; \cap $ GRS$ _k(\boldsymbol{\alpha}, \boldsymbol{\upsilon})^\bot $, which addresses an open problem posed in [Chen et al., IEEE-TIT, 2023]. We also presentd a new approach to generating all self-dual RS codes.

Objective The turnout friction current on-site testing and adjustment involve three major unfavorable aspects of complex processes and high risks, high professional requirements for maintenance personnel, and significant subjective component in determining numerical values, calling for enhancement of the intelligent operation and maintenance level of turnout based on various intelligent algorithms and technologies. Method The characteristics of the four stages of turnout friction current testing curve are analyzed, and an intelligent analysis system for turnout friction current is proposed. The functionality and working principle of the system are elucidated, and standard values and threshold ranges for friction current are established. Based on density clustering algorithm and breadth-first search algorithm, the system can automatically retrieve the turnout friction current value. Screenshots of the system debugging interface are presented to illustrate how the system provides operational suggestions for on-site maintenance personnel in obtaining turnout frictional current values. Result & Conclusion This intelligent system demonstrates excellent usability and achieves the predefined goals of saving maintenance time, reducing maintenance costs, and increasing maintenance efficiency.