Abstract
Background
N6-methyladenosine (m6A) related long noncoding RNAs (lncRNAs) may have prognostic value in bladder cancer for their key role in tumorigenesis and innate immunity.
Methods
Bladder ...cancer transcriptome data and the corresponding clinical data were acquired from the Cancer Genome Atlas (TCGA) database. The m6A-immune-related lncRNAs were identified using univariate Cox regression analysis and Pearson correlation analysis. A risk model was established using least absolute shrinkage and selection operator (LASSO) Cox regression analyses, and analyzed using nomogram, time-dependent receiver operating characteristics (ROC) and Kaplan–Meier survival analysis. The differences in infiltration scores, clinical features, and sensitivity to Talazoparib of various immune cells between low- and high-risk groups were investigated.
Results
Totally 618 m6A-immune-related lncRNAs and 490 immune-related lncRNAs were identified from TCGA, and 47 lncRNAs of their intersection demonstrated prognostic values. A risk model with 11 lncRNAs was established by Lasso Cox regression, and can predict the prognosis of bladder cancer patients as demonstrated by time-dependent ROC and Kaplan–Meier analysis. Significant correlations were determined between risk score and tumor malignancy or immune cell infiltration. Meanwhile, significant differences were observed in tumor mutation burden and stemness-score between the low-risk group and high-risk group. Moreover, high-risk group patients were more responsive to Talazoparib.
Conclusions
An m6A-immune-related lncRNA risk model was established in this study, which can be applied to predict prognosis, immune landscape and chemotherapeutic response in bladder cancer.
The material choice, layer thickness, and twist angle widely enrich the family of van der Waals heterostructures (vdWHs), providing multiple degrees of freedom to engineer their optical and ...electronic properties. The moiré patterns in vdWHs create a periodic potential for electrons and excitons to yield many interesting phenomena, such as Hofstadter butterfly spectrum and moiré excitons. Here, in the as-grown/transferred twisted bilayer MoS2 (tBLMs), one of the simplest prototypes of vdWHs, we show that the periodic potentials of moiré patterns also modify the properties of phonons of its monolayer MoS2 constituent to generate Raman modes related to moiré phonons. These Raman modes correspond to zone-center phonons in tBLMs, which are folded from the off-center phonons in monolayer MoS2. However, the folded phonons related to crystallographic superlattices are not observed in the Raman spectra. By varying the twist angle, the moiré phonons of tBLM can be exploited to map the phonon dispersions of the monolayer constituent. The lattice dynamics of the moiré phonons are modulated by the patterned interlayer coupling resulting from periodic potential of moiré patterns, as confirmed by density functional theory calculations. The Raman intensity related to moiré phonons in all tBLMs are strongly enhanced when the excitation energy approaches the C exciton energy. This study can be extended to various vdWHs to deeply understand their Raman spectra, moiré phonons, lattice dynamics, excitonic effects, and interlayer coupling.
There is increasing evidence that deep sequencing-based T cell repertoire can sever as a biomarker of immune response in cancer patients; however, the characteristics of T cell repertoire including ...diversity and similarity, as well as its prognostic significance in patients with cervical cancer (CC) remain unknown. In this study, we applied a high throughput T cell receptor (TCR) sequencing method to characterize the T cell repertoires of peripheral blood samples from 25 CC patients, 30 cervical intraepithelial neoplasia (CIN) patients and 20 healthy women for understanding the immune alterations during the cervix carcinogenesis. In addition, we also explored the signatures of TCR repertoires in the cervical tumor tissues and paired sentinel lymph nodes from 16 CC patients and their potential value in predicting the prognosis of patients. Our results revealed that the diversity of circulating TCR repertoire gradually decreased during the cervix carcinogenesis and progression, but the circulating TCR repertoires in CC patients were more similar to CIN patients than healthy women. Interestingly, several clonotypes uniquely detected in CC patients tended to share similar CDR3 motifs, which differed from those observed in CIN patients. In addition, the TCR repertoire diversity in sentinel lymphatic nodes from CC patients was higher than in tumor tissues. More importantly, less clonotypes in TCR repertoire of sentinel lymphatic node was associated with the poor prognosis of the patients. Overall, our findings suggested that TCR repertoire might be a potential indicator of immune monitoring and a biomarker for predicting the prognosis of CC patients. Although functional studies of T cell populations are clearly required, this study have expanded our understanding of T cell immunity during the development of CC and provided an experimental basis for further studies on its pathogenesis and immunotherapy.
In the human genome, most 5′ splice sites (~99%) employ the canonical GT dinucleotide whereas a small minority (~1%) use the noncanonical GC dinucleotide. The functionality and pathogenicity of 5′ ...splice site GT>GC (+2T>C) variants have been extensively studied but we know very little about 5′ splice site GC>GT (+2C>T) variants. Herein, we have addressed this deficiency by performing a meta‐analysis of reported +2C>T “pathogenic” variants together with a functional analysis of engineered +2C>T substitutions using a cell culture‐based full‐length gene splicing assay. Our results establish proof of concept that +2C>T variants are qualitatively different from +2T>C variants in terms of their functionality and suggest that, in sharp contrast to +2T>C variants, most if not all +2C>T variants have no pathological relevance. Our findings have important implications for interpreting the clinical relevance of +2C>T variants and understanding the evolutionary switching between GT and GC 5′ splice sites in mammalian genomes.
To date, we know well the functionality and pathogenicity of 5' splice site GT>GC (+2T>C) variants but very little about those of 5' splice site GC>GT (+2C>T) variants. Herein, we performed a meta‐analysis of reported +2C>T “pathogenic” variants together with a functional analysis of engineered +2C>T substitutions. Our analyses establish proof of concept that +2C>T variants are qualitatively different from +2T>C variants in terms of their functionality and pathogenicity.
Chronic pancreatitis (CP) is a chronic inflammatory disease of the pancreas. This study aimed to compare the natural course of alcoholic chronic pancreatitis (ACP) and idiopathic chronic pancreatitis ...(ICP).
CP patients admitted to our center from January 2000 to December 2013 were enrolled. Characteristics were compared between ACP and ICP patients. Cumulative rates of diabetes mellitus (DM), steatorrhea, pancreatic stone, pancreatic pseudocyst, biliary stricture, and pancreatic cancer after the onset and the diagnosis of CP were calculated, respectively. The cumulative rates of DM and steatorrhea after diagnosis of pancreatic stone were also calculated.
A total of 2,037 patients were enrolled. Among them, 19.8% (404/2,037) were ACP and 80.2% (1,633/2,037) were ICP patients. ACP and ICP differs in many aspects, especially in gender, age, smoking, complications, morphology of pancreatic duct, and type of pain. The development of DM, steatorrhea, PPC, pancreatic stone, and biliary stricture were significantly earlier and more common in ACP patients. No significant difference was observed for pancreatic cancer development. There was a rather close correlation between exocrine/endocrine insufficiency and pancreatic stone in ACP patients, which was much less correlated in ICP patients.
The long-term profile of ACP and ICP differs in some important aspects. ACP patients usually have a more severe course of CP. These differences should be recognized in the diagnosis and treatment of CP.
As a global phenomenon, mobile phone addiction has become an increasingly common issue among Chinese university students. Although previous research explored the link between mobile phone addiction ...and mental health, the possible mechanism underlying the above association is unclear. We administered a cross-sectional survey to 585 participants from two universities in Kunming, southwest China, from October 2021 to January 2022. Our results suggested that mobile phone addiction was negatively associated with mental health, and sleep quality partially mediated the relationship between mobile phone addiction and mental health. Furthermore, perceived social support positively moderated the direct effect of sleep quality on mental health, as well as the indirect effect of mobile phone addiction on mental health. These findings provide a new insight into the underlying mechanism by which mobile phone addiction affects university students’ mental health. The results emphasize a necessary task for administrators, health workers, and family members to attach importance to the overuse of mobile phones among university students.
It has long been known that canonical 5′ splice site (5′SS) GT>GC variants may be compatible with normal splicing. However, to date, the actual scale of canonical 5′SSs capable of generating ...wild‐type transcripts in the case of GT>GC substitutions remains unknown. Herein, combining data derived from a meta‐analysis of 45 human disease‐causing 5′SS GT>GC variants and a cell culture‐based full‐length gene splicing assay of 103 5′SS GT>GC substitutions, we estimate that ~15–18% of canonical GT 5′SSs retain their capacity to generate between 1% and 84% normal transcripts when GT is substituted by GC. We further demonstrate that the canonical 5′SSs in which substitution of GT by GC‐generated normal transcripts exhibit stronger complementarity to the 5′ end of U1 snRNA than those sites whose substitutions of GT by GC did not lead to the generation of normal transcripts. We also observed a correlation between the generation of wild‐type transcripts and a milder than expected clinical phenotype but found that none of the available splicing prediction tools were capable of reliably distinguishing 5′SS GT>GC variants that generated wild‐type transcripts from those that did not. Our findings imply that 5′SS GT>GC variants in human disease genes may not invariably be pathogenic.
Based upon complementary data from the meta‐analysis of 45 disease‐causing 5′SS GT>GC variants and the cell culture‐based full‐length gene splicing analysis of 103 5′SS GT>GC substitutions, we have provided a first estimate of ~15–18% for the proportion of canonical GT 5′SSs that are capable of generating between 1% and 84% normal transcripts in case of the substitution of GT by GC. Given that even the retention of 5% normal transcripts can significantly ameliorate a patient's clinical phenotype, our findings imply the potential existence of hundreds or even thousands of disease‐causing 5′SS GT>GC variants that may underlie relatively mild clinical phenotypes. As 5′SS GT>GC variants can also give rise to relatively high levels of wild‐type transcripts, our findings imply that 5′SS GT>GC variants may not invariably be pathogenic in disease‐causative or disease‐associated genes.
Rare pathogenic variants in the SPINK1, PRSS1, CTRC, and CFTR genes have been strongly associated with a risk of developing chronic pancreatitis (CP). However, their potential impact on the age of ...disease onset and clinical outcomes, as well as their potential interactions with environmental risk factors, remain unclear. These issues are addressed here in a large Chinese CP cohort.
We performed targeted next-generation sequencing of the four CP-associated genes in 1061 Han Chinese CP patients and 1196 controls. To evaluate gene-environment interactions, the patients were divided into three subgroups, idiopathic CP (ICP; n = 715), alcoholic CP (ACP; n = 206), and smoking-associated CP (SCP; n = 140). The potential impact of rare pathogenic variants on the age of onset of CP and clinical outcomes was evaluated using the Kaplan-Meier model.
We identified rare pathogenic genotypes involving the SPINK1, PRSS1, CTRC, and/or CFTR genes in 535 (50.42%) CP patients but in only 71 (5.94%) controls (odds ratio = 16.12; P < 0.001). Mutation-positive patients had significantly earlier median ages at disease onset and at diagnosis of pancreatic stones, diabetes mellitus and steatorrhea than mutation-negative ICP patients. Pathogenic genotypes were present in 57.1, 39.8, and 32.1% of the ICP, ACP, and SCP patients, respectively, and influenced age at disease onset and clinical outcomes in all subgroups.
We provide evidence that rare pathogenic variants in the SPINK1, PRSS1, CTRC, and CFTR genes significantly influence the age of onset and clinical outcomes of CP. Extensive gene-environment interactions were also identified.
DMD based lithography system provides the feasibility to achieve multi-point parallel direct writing exposure. However, the distortion of the projection lens in a scanning lithography system not only ...deviates the vertical size (vertical to the scanning direction), but also deviates the center position of an accumulated exposure point from the ideal one. In this work, we report a simple and realizable imaging compensation method, demonstrate as a combination of changing the magnification of the projection lens with loading an appropriately designed mask on DMD to eliminate the effects induced by distortion. With this method, the maximum center deviation of the accumulated exposure point is reduced from 4.3μm to 1.45μm, and the maximum size error is reduced from 0.4μm to 0.1μm with a 0.03% distortion projection lens in simulation. Moreover, we demonstrated the feasibility and effectiveness of the method experimentally by fabricating gratings with high geometry quality in large areas. Therefore, such simple method may have practical significance for improving the lithography quality of DMD-based system.
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