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Hepatocellular carcinoma is the most common form of primary liver cancer and poses a significant challenge to the medical community because of its high mortality rate. In recent years, ferroptosis, a unique form of cell death, has garnered widespread attention. Ferroptosis, which is characterized by iron-dependent lipid peroxidation and mitochondrial alterations, is closely associated with the pathological processes of various diseases, including hepatocellular carcinoma. Long non-coding RNAs (lncRNAs), are a type of functional RNA, and play crucial regulatory roles in a variety of biological processes. In this manuscript, we review the regulatory roles of lncRNAs in the key aspects of ferroptosis, and summarize the research progress on ferroptosis-related lncRNAs in hepatocellular carcinoma.

PurposeTOPBP1 interacting checkpoint and replication regulator (TICRR), a hub gene of the Cdk2-mediated initiation step of DNA replication, has been shown an essential role in tumorigenesis by accelerating the DNA replication of tumor cells.MethodsRT-qPCR was used to detect the mRNA expression of TICRR in LUAD tumors and adjacent normal tissues. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database of LUAD were acquired to analyze the critical role of TICRR expression in survival prognosis and clinicopathology characters in LUAD. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were performed using the R package. The correlation of TICRR expression with immune cell infiltration, RNA epigenetic modification, DNA damage repair (DDR) pathway, and cell metabolism of LUAD was further explored to verify significant conclusions.ResultsTICRR was significantly upregulated in most cancer types, including LUAD, lung squamous cell carcinoma (LUSC), and others. Cox regression analysis indicated the overexpression of TICRR was associated with poor survival in several cancers. In LUAD, TICRR expression was positively correlated with tumor stage and was increased in smoking, male, and high tumor mutational burden (TMB) patients. Enrichment analysis revealed that TICRR could influence tumor proliferation and prognosis via activating pathways involving cell cycle, DNA repair, DNA replication, cysteine metabolism, oxidative phosphorylation, and ubiquitin-mediated proteolysis pathways. Interestingly, high TICRR expression correlated with DDR pathway signature (34 genes), 37 m6A/m5C regulated genes, and some metabolism-regulated genes. Silencing the TICRR gene affects cysteine metabolism and modifies cancer-related pathways, with decreased cell cycle and increased B/T cell receptor signaling. Our TICRR risk model accurately predicts LUAD patient prognosis, validated across GEO datasets, and is integrated with clinical characteristics via a nomogram, facilitating personalized treatment strategies and enhancing patient management.ConclusionsTaken together, TICRR has emerged as a promising prognostic biomarker in lung adenocarcinoma (LUAD), with implications in immune activation, cell cycle regulation, RNA modification, and tumor energy metabolism. These findings suggest that TICRR could serve as a viable therapeutic target and a reliable prognostic indicator for LUAD.

BackgroundColorectal cancer (CRC) is a prevalent malignancy with diverse molecular characteristics. The NGS-based approach enhances our comprehension of genomic landscape of CRC and may guide future advancements in precision oncology for CRC patients.MethodIn this research, we conducted an analysis using Next-Generation Sequencing (NGS) on samples collected from 111 individuals who had been diagnosed with CRC. We identified somatic and germline mutations and structural variants across the tumor genomes through comprehensive genomic profiling. Furthermore, we investigated the landscape of driver mutations and their potential clinical implications.ResultsOur findings underscore the intricate heterogeneity of genetic alterations within CRC. Notably, BRAF, ARID2, KMT2C, and GNAQ were associated with CRC prognosis. Patients harboring BRAF, ARID2, or KMT2C mutations exhibited shorter progression-free survival (PFS), whereas those with BRAF, ARID2, or GNAQ mutations experienced worse overall survival (OS). We unveiled 80 co-occurring and three mutually exclusive significant gene pairs, enriched primarily in pathways such as TP53, HIPPO, RTK/RAS, NOTCH, WNT, TGF-Beta, MYC, and PI3K. Notably, co-mutations of BRAF/ALK, BRAF/NOTCH2, BRAF/CREBBP, and BRAF/FAT1 correlated with worse PFS. Furthermore, germline AR mutations were identified in 37 (33.33%) CRC patients, and carriers of these variants displayed diminished PFS and OS. Decreased AR protein expression was observed in cases with AR germline mutations. A four-gene mutation signature was established, incorporating the aforementioned prognostic genes, which emerged as an independent prognostic determinant in CRC via univariate and multivariate Cox regression analyses. Noteworthy BRAF and ARID2 protein expression decreases detected in patients with their respective mutations.ConclusionThe integration of our analyses furnishes crucial insights into CRC’s molecular characteristics, drug responsiveness, and the construction of a four-gene mutation signature for predicting CRC prognosis.

Background: Pediatric gliomas (PGs) are highly aggressive and predominantly occur in young children. In pediatric gliomas, abnormal expression of Homeobox (HOX) family genes (HFGs) has been observed and is associated with the development and progression of the disease. Studies have found that overexpression or underexpression of certain HOX genes is linked to the occurrence and prognosis of gliomas. This aberrant expression may contribute to the dysregulation of important pathological processes such as cell proliferation, differentiation, and metastasis. This study aimed to propose a novel HOX-related signature to predict patients’ prognosis and immune infiltrate characteristics in PGs.Methods: The data of PGs obtained from publicly available databases were utilized to reveal the relationship among abnormal expression of HOX family genes (HFGs), prognosis, tumor immune infiltration, clinical features, and genomic features in PGs. The HFGs were utilized to identify heterogeneous subtypes using consensus clustering. Then random forest-supervised classification algorithm and nearest shrunken centroid algorithm were performed to develop a prognostic signature in the training set. Finally, the signature was validated in an internal testing set and an external independent cohort.Results: Firstly, we identified HFGs significantly differentially expressed in PGs compared to normal tissues. The individuals with PGs were then divided into two heterogeneous subtypes (HOX-SI and HOX-SII) based on HFGs expression profiles. HOX-SII showed higher total mutation counts, lower immune infiltration, and worse prognosis than HOX-SI. Then, we constructed a HOX-related gene signature (including HOXA6, HOXC4, HOXC5, HOXC6, and HOXA-AS3) based on the cluster for subtype prediction utilizing random forest supervised classification and nearest shrunken centroid algorithm. The signature was revealed to be an independent prognostic factor for patients with PGs by multivariable Cox regression analysis.Conclusion: Our study provides a novel method for the prognosis classification of PGs. The findings also suggest that the HOX-related signature is a new biomarker for the diagnosis and prognosis of patients with PGs, allowing for more accurate survival prediction.

This paper explores dust acoustic waves (DAWs)’ instability in two dimensional nonuniform complex plasmas. For this purpose, the dispersion relation is obtained using the method of separation of variables. In the process of linearizing the hydrodynamic equations describing the characteristics of two dimensional nonuniform complex plasma equations, the temporal and spatial dependence of all perturbations is assumed to be proportional to A1(x, y)exp[−iωt]. It is shown that the inhomogeneities in indifferent directions have different influences on the linear dispersion characteristics of DAWs. The numerical results show that the present research results are very important in the phenomenon of space astrophysical and experimental plasmas.

BackgroundColorectal cancer (CRC) is the third most prevalent malignancy and the one of most lethal cancer. Metastatic CRC (mCRC) is the third most common cause of cancer deaths worldwide. DNA damage response (DDR) genes are closely associated with the tumorigenesis and development of CRC. In this study, we aimed to construct a DDR-related gene signature for predicting the prognosis of mCRC patients.MethodsThe gene expression and corresponding clinical information data of CRC/mCRC patients were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. A prognostic model was obtained and termed DDRScore by the multivariate Cox proportional hazards regression in the patients with mCRC. The Kaplan-Meier (K-M) and Receiver Operating Characteristic (ROC) curves were employed to validate the predictive ability of the prognostic model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed for patients between the high-DDRscore and low-DDRscore groups.ResultsWe constructed a prognostic model consisting of four DDR-related genes (EME2, MSH4, MLH3, and SPO11). Survival analysis showed that patients in the high-DDRscore group had a significantly worse OS than those in the low-DDRscore group. The area under the curve (AUC) value of the ROC curve of the predictive model is 0.763 in the training cohort GSE72970, 0.659 in the stage III/IV colorectal cancer (CRC) patients from The Cancer Genome Atlas (TCGA) data portal, and 0.639 in another validation cohort GSE39582, respectively. GSEA functional analysis revealed that the most significantly enriched pathways focused on nucleotide excision repair, base excision repair, homologous recombination, cytokine receptor interaction, chemokine signal pathway, cell adhesion molecules cams, ECM-receptor interaction, and focal adhesion.ConclusionThe DDRscore was identified as an independent prognostic and therapy response predictor, and the DDR-related genes may be potential diagnosis or prognosis biomarkers for mCRC patients.

Background: Prostate cancer (PCa) is the second most common cancer among men worldwide. Perineural invasion (PNI) was a prominent characteristic of PCa, which was recognized as a key factor in promoting PCa progression. As a complex and heterogeneous disease, its true condition is difficult to explain thoroughly with conventional bulk RNA sequencing. Thus, an improved understanding of PNI-PCa progression at the single-cell level is needed.Methods: In this study, we performed scRNAseq on tumor tissues of three PNI-PCa patients. Principal component analysis (PCA) and Uniform manifold approximation and projection (UMAP) were used to reduce dimensionality and visualize the cellular composition of tumor tissues. The differently expressed genes among each cluster were identified by EdgeR. GO enrichment analysis was used to understand the roles of genes within the clusters. Pseudotime cell trajectory was used to reveal the molecular pathways underlying cell fate decisions and identify genes whose expression changed as the cells underwent transition. We applied CellPhoneDB to identify cell-cell interactions among the epithelial and neural cells in PNI-PCa.Results: Analysis of the ∼17,000 single-cell transcriptomes in three PNI prostate cancer tissues, we identified 12 major cell clusters, including neural cells and two epithelial subtypes with different expression profiles. We found that basal/intermediate epithelial cell subtypes highly expressed PCa progression-related genes, including PIGR, MMP7, and AGR2. Pseudotime trajectory analysis showed that luminal epithelial cells could be the initiating cells and transition to based/intermediate cells. Gene ontology (GO) enrichment analysis showed that pathways related to cancer progressions, such as lipid catabolic and fatty acid metabolic processes, were significantly enriched in basal/intermediate cells. Our analysis also suggested that basal/intermediate cells communicate closely with neural cells played a potential role in PNI-PCa progression.Conclusion: These results provide our understanding of PNI-PCa cellular heterogeneity and characterize the potential role of basal/intermediate cells in the PNI-PCa progression.

IntroductionColorectal cancer (CRC) is one of the most prevalent cancers globally with a high mortality rate. Predicting prognosis using disease progression and cancer pathologic stage is insufficient, and a prognostic factor that can accurately evaluate patient prognosis needs to be developed. In this study, we aimed to infer a prognostic gene signature to identify a functional signature associated with the prognosis of CRC patients.MethodsFirst, we used univariate Cox regression, least absolute shrinkage and selection operator (lasso) regression, and multivariate Cox regression analyses to screen genes significantly associated with CRC patient prognosis, from colorectal cancer RNA sequencing data in The Cancer Genome Atlas (TCGA) database. We then calculated the risk score (RS) for each patient based on the expression of the nine candidate genes and developed a prognostic signature.ResultsBased on the optimal cut-off on the receiver operating characteristic (ROC) curve, patients were separated into high- and low-risk groups, and the difference in overall survival between the two groups was examined. Patients in the low-risk group had a better overall survival rate than those in the high-risk group. The results were validated using the GSE72970, GSE39582, and GSE17536 Gene Expression Omnibus (GEO) datasets, and the same conclusions were reached. ROC curve test of the RS signature also indicated that it had excellent accuracy. The RS signature was then compared with traditional clinical factors as a prognostic indicator, and we discovered that the RS signature had superior predictive ability.ConclusionThe RS signature developed in this study has excellent predictive power for the prognosis of patients with CRC and broad applicability as a prognostic indicator for patients.

Lymphatic metastasis influences clinical treatment and prognosis of patients with non-small-cell lung cancer (NSCLC). There is an urgency to understand the molecular features and mechanisms of lymph node metastasis. We analyzed the molecular features on pairs of the primary tumor and lymphatic metastasis tissue samples from 15 NSCLC patients using targeted next-generation sequencing. The potential metastasis-related genes were screened from our cohort based on cancer cell fraction. After filtering with gene functions, candidate metastasis-related events were validated in the MSK cohort with Fisher’s exact test. The molecular signature and tumor mutational burden were similar in paired samples, and the average mutational concordance was 42.0% ± 28.9%. Its metastatic mechanism is potentially a linear progression based on the metastatic seeding theory. Furthermore, mutated ataxia telangiectasia mutated and Rad3-related (ATR) and tet methylcytosine dioxygenase 2 (TET2) genes were significantly enriched in lymphatic metastases (p ≤ 0.05). Alterations in these two genes could be considered metastasis-related driving events. Mutated ATR and TET2 might play an active role in the metastasis of lymph nodes with NSCLC. More case enrollment and long-term follow-up will further verify the clinical significance of these two genes.

BackgroundHigh grade serous ovarian cancer (HGSOC) is the most common subtype of ovarian cancer. Although platinum-based chemotherapy has been the cornerstone for HGSOC treatment, nearly 25% of patients would have less than 6 months of interval since the last platinum chemotherapy, referred to as platinum-resistance. Currently, no precise tools to predict platinum resistance have been developed yet.MethodsNinety-nine HGSOC patients, who have finished cytoreductive surgery and platinum-based chemotherapy in Peking University Third Hospital from 2018 to 2019, were enrolled. Whole-genome sequencing (WGS) and whole-exome sequencing (WES) were performed on the collected tumor tissue samples to establish a platinum-resistance predictor in a discovery cohort of 57 patients, and further validated in another 42 HGSOC patients.ResultsA high prevalence of alterations in DNA damage repair (DDR) pathway, including BRCA1/2, was identified both in the platinum-sensitive and resistant HGSOC patients. Compared with the resistant subgroup, there was a trend of higher prevalence of homologous recombination deficiency (HRD) in the platinum-sensitive subgroup (78.95% vs. 47.37%, p=0.0646). Based on the HRD score, microhomology insertions and deletions (MHID), copy number changes load, duplication load of 1–100 kb, single nucleotide variants load, and eight other mutational signatures, a combined predictor of platinum-resistance, named as DRDscore, was established. DRDscore outperformed in predicting the platinum-sensitivity than the previously reported biomarkers with a predictive accuracy of 0.860 at a threshold of 0.7584. The predictive performance of DRDscore was validated in an independent cohort of 42 HGSOC patients with a sensitivity of 90.9%.ConclusionsA multi-genomic signature-based analysis enabled the prediction of initial platinum resistance in advanced HGSOC patients, which may serve as a novel assessment of platinum resistance, provide therapeutic guidance, and merit further validation.

Plasma waves may become unstable in the channel of field effect transistors (FETs) with asymmetric boundary conditions on source and drain, which is known as Dyakonov-Shur instability. In this letter, we extend the Dyakonov-Shur instability to the quantum gated cylindrical FET and obtain the dispersion equations describing unstable terahertz (THz) plasma waves using quantum cylindrical hydrodynamic equations. Research results show that the length of the channel and the wave vector of the circumferential direction inhibit the instability increment; however, the quantum effect, the radius of the channel, and the electron temperature enhance the instability increment. The oscillation frequency increases with the increase in the quantum effect, the wave vector of the circumferential direction, and the electron temperature, but the oscillation frequency increases with the decrease in the length and radius of the channel. Compared with the one-dimensional rectangular FET, THz plasma waves in the two-dimensional cylindrical FET have a higher oscillation frequency.

There remain some difficulties in delimitation of related genera or sibling species for cantharid beetles, because the traditionally taxonomic method and morphological characters have not been updated or introduced. In the present study, we firstly use the landmark-based geometric morphometrics to analyze and compare the hind wings of nine species belonging to three genera of Cantharinae to ascertain whether this approach may be used as a reliable method in the study of the taxonomy of this group. The results show that the shape differences of the hind wings among genera seem more variable than that within each genus, and the variations for each species are different from one another, as shown in the principal component analyses. And the canonical variates analyses show that there are significant differences among the genera and the species of each genus, which demonstrates that the hind wing shape can be diagnostic for both generic and specific identification of the cantharid beetles. This study sheds new light into clarifying the taxonomic uncertainties of Cantharidae, and lays a foundation for further studies on the evolution of the cantharid hind wing shape.

Six new species of Lycocerus Gorham are described, L. gracilicornis sp. n. (China: Sichuan), L. longihirtus sp. n. (China: Yunnan), L. sichuanus sp. n. (China: Sichuan), L. hubeiensis sp. n. (China: Hubei), L. napolovi sp. n. (Vietnam: Sa Pa) and L. quadrilineatus sp. n. (Vietnam: Sa Pa), and provided with illustrations of habitus, antennae and aedeagi of male or and antennae, abdominal sternites VIII and genitalia of female. L. rubroniger Švihla, 2011 is synonymized with L. obscurus Pic, 1916. L. hickeri Pic, 1934 and L. obscurus are provided with illustrations of abdominal sternites VIII of female. Nine species are recorded from China for the first time, L. bicoloripennis (Pic, 1924), L. caliginostus Gorham, 1889, L. jendeki Švihla, 2005, L. malaisei (Wittmer, 1995), L. obscurus, L. olivaceus (Wittmer, 1995), L. purpureus Kazantsev, 2007, L. ruficornis (Wittmer, 1995) and L. semiextensus (Wittmer, 1995), and L. ruficornis is also recorded for Myanmar for the first time.

Two new species of Fissocantharis Pic are described, F. bifoveatus sp. n. (CHINA: Yunnan) and F. acuticollis sp. n. (CHINA: Zhejiang, Fujian, Guangdong, Hunan). F. pieli (Pic, 1937) is redescribed and F. kontumensis Wittmer, 1989 is provided with a supplementary description. F. shanensis (Wittmer, 1997) is synonymized with F. kontumensis. For the above four species, illustrations of male genitalia are provided, for the latter three also photos of female genitalia and abdominal sternites VIII, and for the new species photos of male habitus and antennae are presented. Additionally, the specific name of F. wittmeri (Y. Yang et X. Yang, 2009), preoccupied by F. wittmeri (Kazantsev, 2007), is replaced by F. walteri Y. Yang et X. Yang, nom. n. And F. wittmeri (Kazantsev, 2007) is found to be a junior objective synonym of F. denominata (Wittmer, 1997).

Abstract Asymptomatic Leucine-Rich Repeat Kinase 2 Gene (LRRK2) carriers are at risk for developing Parkinson's disease (PD). We studied presymptomatic substantia nigra pars compacta (SNc) regional neurodegeneration in asymptomatic LRRK2 carriers compared to idiopathic PD patients using neuromelanin-sensitive MRI technique (NM-MRI). Fifteen asymptomatic LRRK2 carriers, 22 idiopathic PD patients, and 30 healthy controls (HCs) were scanned using NM-MRI. We computed volume and contrast-to-noise ratio (CNR) derived from the whole SNc and the sensorimotor, associative, and limbic SNc regions. An analysis of covariance was performed to explore the differences of whole and regional NM-MRI values among the groups while controlling the effect of age and sex. In whole SNc, LRRK2 had significantly lower CNR than HCs but non-significantly higher volume and CNR than PD patients, and PD patients significantly lower volume and CNR compared to HCs. Inside SNc regions, there were significant group effects for CNR in all regions and for volumes in the associative region, with a trend in the sensorimotor region but no significant changes in the limbic region. PD had reduced volume and CNR in all regions compared to HCs. Asymptomatic LRRK2 carriers showed globally decreased SNc volume and CNR suggesting early nigral neurodegeneration in these subjects at risk of developing PD.

Summary: Background: Premature ovarian failure (POF) is a prevalent and severe condition that impairs female health but there is currently no effective treatment available to restore ovarian function. Human amniotic epithelial cells (hAECs) exhibit ovarian protection in pre-clinical models. Thus, we conducted a single-arm, phase 1 clinical trial to assess the safety and efficacy of allogenic hAECs in treating POF. Methods: A total of 35 patients received 6 × 107 hAECs via ovarian artery and completed a five-month follow-up from December 30, 2020 to January 31, 2022. The follow-up assessments were conducted at various intervals after hAECs treatment, including one month (Visit-1, V-1), three months (Visit-2, V-2), and five months (Visit-3, V-3) post-treatment. The primary endpoints were incidence of adverse events (AEs), and clinically significant laboratory abnormalities. Secondary endpoints included evaluation of transvaginal ultrasound results, sex hormone levels, Menopausal Quality of Life (MENQOL) questionnaire, as well as reproductive indicators. This trial was registered at www.clinicaltrials.gov as NCT02912104. Findings: No serious AEs were observed throughout the five-month follow-up period. The most common AE was hematoma (7/35, 20.00%), and other AEs include pelvic pain (4/35, 11.43%), fever (2/35, 5.71%), anaphylaxis (2/35, 5.71%), and hepatotoxicity (1/35, 2.86%). After hAECs transplantation (hAECT), significant improvements were observed in the levels of endometrial thickness, left ovarian volume, sex hormones (follicle-stimulating hormone (FSH) and estradiol (E2)), and MENQOL scores in all patients during the five-month follow-up period. Among them, 13 participants (37.14%) experienced spontaneous menstrual bleeding, and 20.00% (7/35) reported more than one regular menstrual bleeding post-hAECT. In this response group, significant improvements were observed in endometrial thickness, left ovarian volume, levels of FSH, E2, anti-Müllerian hormone (AMH), and MENQOL scores one month after hAECT in comparison to pre-hAECT. Interpretation: hAECT via ovarian artery is safe, well-tolerated and temporarily ameliorates endometrial thickness, ovarian size, hormone levels, and menopausal symptoms in POF patients. Further randomized controlled trial of hAECs with longer follow-up period and a larger sample size is warranted. Funding: National Natural Science Foundation of China (No. 82271664), the Interdisciplinary Program of Shanghai Jiao Tong University (YG2022ZD028), the Shanghai Municipal Health Committee (202240345), Shanghai Key Laboratory of Embryo Original Diseases (No. Shelab2022ZD01), Shanghai Municipal Education Commission (No. 20152236), and National Key Research and Development Program of China (No. 2018YFC1004802), Shanghai Clinical Research Center for Cell Therapy, China (No. 23J41900100).

PurposeTo determine the 90 percent effective dose (ED90) of intrathecal sufentanil combined with ropivacaine 2.5 mg for labor analgesia and observe its safety for parturients and neonates.MethodsWe conducted a prospective, double-blind, biased coin up-and-down study. We injected a fixed 2.5 mg ropivacaine combined with a designated dose of sufentanil intrathecally to observe the labor analgesic effect. The initial dose of sufentanil was assigned 1.0 μg, and the remaining doses were assigned as per the biased coin up-and-down method. The criterion of successful response was defined as VAS ≤ 30 mm after intrathecal injection at 10 min. Safety was evaluated in terms of maternal and neonatal outcomes.ResultsThe ED90 dose of intrathecal sufentanil combined with ropivacaine 2.5 mg (0.1%, 2.5 mL) was 2.61 μg (95% CI, 2.44 to 2.70 μg) by isotonic regression. No respiratory depression, hypotension, or motor block was observed. Thirty-one (77.5%) parturients complained of pruritus, and 14 (35.0%) suffered nausea and vomiting. Three neonates reported a 1 min Apgar score of ≤7, and none reported a 5 min Apgar score of ≤7.ConclusionThe ED90 of intrathecal sufentanil combined with ropivacaine 2.5 mg for labor analgesia was 2.61 μg. The dose is safe for parturients and neonates.

Abstract Locus coeruleus (LC) is severely affected in Parkinson’s Disease (PD). However, alterations in LC-related resting-state networks (RSNs) in PD remain unclear. We used resting-state functional MRI to investigate the alterations in functional connectivity (FC) of LC-related RSNs and the associations between RSNs changes and clinical features in idiopathic rapid eye movement sleep behavior disorder (iRBD) and PD patients with (PDRBD+) and without RBD (PDRBD−). There was a similarly disrupted FC pattern of LC-related RSNs in iRBD and PDRBD+ patients, whereas LC-related RSNs were less damaged in PDRBD− patients than that in patients with iRBD and PDRBD+. The FC of LC-related RSNs correlated with cognition and duration in iRBD, depression in PDRBD−, and cognition and severity of RBD in patients with PDRBD+. Our findings demonstrate that LC-related RSNs are significantly disrupted in the prodromal stage of α-synucleinopathies and proposed body-first PD (PDRBD+), but are less affected in brain-first PD (PDRBD−).

Background: Recent animal model studies have suggested that the parafascicular nucleus has the potential to be an effective deep brain stimulation target for Parkinson's disease. However, our knowledge on the role of the parafascicular nucleus in Parkinson's disease patients remains limited. Objective: We aimed to investigate the functional alterations of the parafascicular nucleus projections in Parkinson's disease patients. Methods: We enrolled 72 Parkinson's disease patients and 60 healthy controls, then utilized resting-state functional MRI and spectral dynamic causal modeling to explore the effective connectivity of the bilateral parafascicular nucleus to the dorsal putamen, nucleus accumbens, and subthalamic nucleus. The associations between the effective connectivity of the parafascicular nucleus projections and clinical features were measured with Pearson partial correlations. Results: Compared with controls, the effective connectivity from the parafascicular nucleus to dorsal putamen was significantly increased, while the connectivity to the nucleus accumbens and subthalamic nucleus was significantly reduced in Parkinson's disease patients. There was a significantly positive correlation between the connectivity of parafascicular nucleus-dorsal putamen projection and motor deficits. The connectivity from the parafascicular nucleus to the subthalamic nucleus was negatively correlated with motor deficits and apathy, while the connectivity from the parafascicular nucleus to the nucleus accumbens was negatively associated with depression. Conclusion: The present study demonstrates that the parafascicular nucleus-related projections are damaged and associated with clinical symptoms of Parkinson's disease. Our findings provide new insights into the impaired basal ganglia-thalamocortical circuits and give support for the parafascicular nucleus as a potential effective neuromodulating target of the disease.

Abstract Neuroimaging studies suggest a pivotal role of amygdala dysfunction in non-motor symptoms (NMS) of Parkinson’s disease (PD). However, the relationship between amygdala subregions (the centromedial (CMA), basolateral (BLA) and superficial amygdala (SFA)) and NMS has not been delineated. We used resting-state functional MRI to examine the PD-related alterations in functional connectivity for amygdala subregions. The left three subregions and right BLA exhibited between-group differences, and were commonly hypo-connected with the frontal, temporal, insular cortex, and putamen in PD. Each subregion displayed distinct hypoconnectivity with the limbic systems. Partial least-squares analysis revealed distinct amygdala subregional involvement in diverse NMS. Hypo-connectivity of all four subregions was associated with emotion, pain, olfaction, and cognition. Hypo-connectivity of the left SFA was associated with sleepiness. Our findings highlight the hypofunction of the amygdala subregions in PD and their preliminary associations with NMS, providing new insights into the pathogenesis of NMS.

Abstract Background The triglyceride–glucose index (TyG index), an alternative indicator of peripheral insulin resistance (IR), is associated with cardiovascular disease (CVD) in the general population. The aim of this research was to determine the correlation between early-onset stroke and the TyG index among young Chinese adults. Methods Participants (age ≤ 40 years) who attended their first physical examination in Kailuan General Hospital or its 11 subsidiary hospitals between 2006 and 2012 were enrolled. The subjects were divided into four equal points according to the quartile of the TyG index, with the lowest quartile (Q1) as the reference group. A Cox proportional hazard model was employed to assess the correlation between early-onset stroke incidence and the TyG index. Restricted cubic spline analysis was further conducted to examine nonlinear associations. The TyG index was calculated as Ln [Triglyceride (TG, mg/dL) × Fasting Blood Glucose (FBG, mg/dL)/2]. Results Overall, 35,999 subjects met the inclusion criteria. Their mean age was 30.8 ± 5.7 years, and 77.1% of subjects were males. During a median observation period of 11 years, 281 stroke events occurred (62 hemorrhagic strokes and 219 ischemic strokes). Compared to the Q1 group (as the lowest group), subjects in groups Q2-Q4 had significantly higher risks of early-onset stroke (P