Comparison of the performance of NIPT and NIPT-plus for fetal chromosomal aneuploidy and high Z-score increases the positive predictive value.

OBJECTIVE: To evaluate non-invasive prenatal testing (NIPT) and expanded non-invasive prenatal testing (NIPT-plus) for detecting aneuploidies at different sequencing depths and assess Z-score accuracy in predicting trisomies 21, 18, 13, 45X, and 47XXX. METHODS: Pregnancies with positive NIPT or NIPT-plus results detected at the prenatal diagnosis center of Nanfang Hospital were included in this retrospective study, between January 2017 and December 2022. Invasive prenatal diagnostic results were collected. Logistic regression analyses were used to study the relationship between Z-score and positive predictive value (PPV). Optimal cut-off values were obtained based on receiver operating characteristic analysis, and PPVs were calculated in different groups. RESULTS: We evaluated 1348 pregnant women with positive results, including 930 reported by NIPT and 418 reported by NIPT-plus. NIPT reported significantly more rare chromosomal aneuploidies (RCAs), and NIPT-plus had a significantly higher PPV for trisomy 21 (T21). Logistic regression analyses showed a significant association (P < 0.001) between Z-score and PPVs for T21 and trisomy 18 (T18). A linear relationship was observed between fetal fraction (FF) and Z-values in the true positive cases of T21 and T18.The high Z-score group had significantly higher PPVs than the low Z-score group for T21, T18, trisomy 13, and 47XXX, but not for 45X. CONCLUSION: The Z-score is helpful in assessing NIPT or NIPT-plus results. Therefore, we suggest including the Z-score and FF in the results. By combining the Z-score, FF, and maternal age, clinicians can interpret NIPT results more accurately and improve personal counsel to reduce patients' anxiety.

Clinical experience sharing on gastric microneuroendocrine tumors: A case report.

BACKGROUND: The majority of gastric neuroendocrine tumors (G-NENs) are present in various lesions under endoscopy, and they can be polypoid uplifts, submucosal tumors or papules, erosions, and ulcers. The lesions are mostly confined to the mucosal or submucosal layer, usually less than 2 cm, and exclusively localized to the gastric body or fundus. In type 1 G-NENs, about 22% of cases have no visible lesions under an endoscope, and such lesions can only be detected via biopsies (microcarcinoids). CASE SUMMARY: A 67-year-old female patient with appetite loss for more than half a year and personal history of hyperthyroidism was admitted to our hospital. After admission, a random multi-point biopsy was performed on the gastric body, fundus, angle, and antrum through gastroscopy. Pathological examination showed chronic severe atrophic gastritis in the fundus and body of the stomach. The small curvature of the gastric body, the anterior wall of the gastric body, and the posterior wall of the gastric body displayed proliferation of intestinal chromaffin cells. The curvature of the gastric body showed neuroendocrine tumor G1 (carcinoid), while the antrum and angle of the stomach showed mild atrophic gastritis with mild intestinal metaplasia. Immunohistochemical examination showed that the greater curvature of the gastric body was Syn (+), CgA (+), and Ki-67 (+, approximately 1%), which is consistent with neuroendocrine tumors (grade 1). Regular gastroscopy and biopsy should be performed every one to two years to monitor G-NENs. CONCLUSION: In the case under study, the patient did not have any visible raised lesions under a gastroscope, and the lesions were found only after a random biopsy. This article combines the endoscopic manifestations and clinical features of the lesions in this case to improve the diagnosis of G-NENs.

Effect of Gut Microbiota-Mediated Tryptophan Metabolism on Inflammaging in Frailty and Sarcopenia.

Frailty syndrome refers to the nonspecific state of increased body vulnerability and decreased antistress and recovery abilities after stress during aging. Sarcopenia is the major component of frailty and is characterized by the gradual loss of muscle mass, strength, and function with age. Inflammaging is the gradual increase in inflammatory status during aging, and it disrupts immune tolerance, causes physiological changes in tissues, organs, and normal cells, and is related to frailty and sarcopenia. The gut microbiota is an extremely complex and diverse microbial community that coevolves with the host. The composition and structure of the gut microbiota and the metabolism of tryptophan (Trp) significantly change in older adults with frailty and sarcopenia. The gut microbiota participates in regulating the Trp metabolic pathways of kynurenine (Kyn), 5-hydroxytryptamine (5-HT), and indole in the gastrointestinal tract. The Trp metabolites derived from the gut microbiota may synergistically promote the occurrence of age-related frailty and sarcopenia by promoting inflammation in the intestines, nervous system, and muscles. The role and mechanisms of the gut microbiota, Trp metabolism, and inflammaging in age-related frailty and sarcopenia may be a worthwhile research direction to help promote healthy aging.

Engineering Interfacial Fast Ion Channels toward Highly Stable Zn Metal Batteries.

The development of aqueous zinc-ion batteries (AZIBs) is hindered by dendrites and side reactions, such as interfacial byproducts, corrosion, and hydrogen evolution. The construction of an artificial interface protective layer on the surface of the zinc anode has been extensively researched due to its strong operability and potential for large-scale application. In this study, we have designed an organic hydrophobic hybrid inorganic intercalation composite coating to achieve stable Zn2+ plating/stripping. The hydrophobic poly(vinylidene fluoride) (PVDF) effectively prevents direct contact between free water and the zinc anode, thereby mitigating the risk of dendrite formation. Simultaneously, the inorganic layer of vanadium phosphate (VOPO4·2H2O) after the insertion of polyaniline (PA) establishes a robust ion channel for facilitating rapid transport of Zn2+, thus promoting uniform electric field distribution and reducing concentration polarization. As a result, the performance of the modified composite PVDF/PA-VOP@Zn anode exhibited significant enhancement compared with that of the bare zinc anode. The assembled symmetric cell exhibits an exceptionally prolonged lifespan of 3070 h at a current density of 1 mA cm-2, while the full battery employing KVO as the cathode demonstrates a remarkable capability to undergo 2000 cycles at 5 A g-1 with a capacity retention rate of 78.2%. This study offers valuable insights into the anodic modification strategy for AZIBs.

Regulating Interlayer-Spacing of Vanadium Phosphates for High-Capacity and Long-Life Aqueous Iron-Ion Batteries.

Although the research on aqueous batteries employing metal as the anode is still mainly focused on the aqueous zinc-ion battery, aqueous iron-ion batteries are considered as promising aqueous batteries owing to the lower cost, higher specific capacity, and better stability. However, the sluggish Fe2+ (de)intercalation leads to unsatisfactory specific capacity and poor electrochemical stability, which makes it difficult to find cathode materials with excellent electrochemical properties. Herein, phenylamine (PA)-intercalated VOPO4 materials with expanded interlayer spacing are synthesized and applied successfully in aqueous iron-ion batteries. Owing to enough diffusion space from the expanded interlayer, which can boost fast Fe2+ diffusion, the aqueous iron-ion battery shows a high specific capacity of 170 mAh g-1 at 0.2 A g-1 , excellent rate performance, and cycle stability (96.2% capacity retention after 2200 cycles). This work provides a new direction for cathode material design in the development of aqueous iron-ion batteries.

Understanding the Super-Theoretical Capacity Behavior of VO2 in Aqueous Zn Batteries.

VO2 material, as a promising intercalation host, is widely investigated not only in aqueous lithium-ion batteries, but also in aqueous zinc-ion batteries (AZIBs) owing to its stable tunnel-like framework and multivalence of vanadium. Different from lithium-ion storage, VO2 can provide higher capacity when storing zinc ions, even exceeding its theoretical capacity (323 mAh g-1 ), but the specific reason for this unconventional performance in AZIBs is still unclear. The present study proposes a catalytic oxygen evolution reaction (OER) coupled with an interface oxidation mechanism of VO2 during the initial charging to a high voltage. This coupling induces a phase transformation of VO2 into a high oxidation state of V5 O12 ∙6H2 O, enabling a nearly two-electron reaction and providing additional zinc storage sites to achieve super-theoretical capacity. Furthermore, it is demonstrated that these vanadium oxide cathodes (V2 O3 , VO2 , and V2 O5 ) will all undergo phase change after the first charge or short cycle. Notably, water molecules participate in the final formation of layered vanadium-based hydrate, highlighting their crucial role as "pillars" for stabilizing the structure. This work significantly enhances the understanding of vanadium-based oxide cathodes.

Fecal microbial biomarkers in older adults with autoimmune diseases.

Aim: To analyze the alterations in the fecal microbiota of older adults with autoimmune disease and determine the diagnostic capabilities of microbial biomarkers. Methods: The raw data of fecal samples from 444 older adults from the publicly available American Gut Project database was analyzed. Results: It was found that there were no significant differences in the microbiota richness and evenness between older adults with autoimmune disease and healthy controls. However, significant differences were observed in the microbiota composition and structure. The subject operating characteristic curve of the eight key microbiota was obtained, and the area under curve value was 70.0%. Conclusion: Older adults with autoimmune disease showed changes in intestinal microbiota composition, which can be used as microbial biomarkers.

Lower haemoglobin-to-red blood cell distribution width ratio is independently associated with frailty in community-dwelling older adults: a cross-sectional study.

OBJECTIVES: The importance of blood cell markers in frailty has been studied. However, research on haemoglobin-to-red blood cell distribution width ratio (HRR) and frailty in older persons is still limited. We investigated the association between HRR and frailty in older adults. DESIGN: Cross-sectional population-based study. SETTING: Community-dwelling older adults older than 65 years were recruited from September 2021 to December 2021. PARTICIPANTS: A total of 1296 community-dwelling older adults (age ≥65 years) in Wuhan were included in the study. MAIN OUTCOME MEASURES: The main outcome was the presence of frailty. The Fried Frailty Phenotype Scale was used to evaluate the frailty status of the participants. Multivariable logistic regression analysis was performed to determine the relationship between HRR and frailty. RESULTS: A total of 1296 (564 men) older adults were included in this cross-sectional study. Their mean age was 70.89±4.85 years. Receiver operating characteristic curve analysis showed that HRR is a good predictor of frailty in older people, the area under the curve (AUC) was 0.802 (95% CI: 0.755 to 0.849), and the highest sensitivity was 84.5% and the specificity was 61.9% with the optimal critical values 9.97 (p<0.001). Multiple logistic regression analysis indicated that lower HRR (<9.97) (OR: 3.419, 1.679 to 6.964, p=0.001) is independently associated with frailty in older people, even after adjusting confounding factors. CONCLUSION: Lower HRR is closely associated with an increased risk of frailty in older people. Lower HRR may be an independent risk factor for frailty in community-dwelling older adults.

Achieving high performance in aqueous iron-ion batteries using tunnel-like VO2 as a cathode material.

The research on aqueous iron-ion batteries (AIIBs) is still in its early stages and highly limited by the lack of suitable cathode materials. In this study, we propose using tunnel-like VO2 as a cathode material, which delivers a high capacity of 198 mA h g-1 at 0.2 A g-1. Besides, the AIIB exhibits appreciable cycling performance, retaining 78.9% of its initial capacity after 200 cycles. The unique structure of VO2 and the multiple valence states of vanadium in VO2 enable the reversible storage of Fe2+ during cycling. This work presents a new choice for the cathode and considerable development prospects in AIIBs.

Non-invasive prenatal test findings in 41,819 pregnant women: results from a clinical laboratory in southern China.

BACKGROUND: This paper evaluated the clinical utility of massively parallel sequencing-based non-invasive prenatal testing (NIPT) for detecting trisomy 21 (T21), T18, T13, sex chromosome aneuploidies (SCA), and rare chromosome aneuploidies (RCA) among the data collected by a clinical laboratory in southern China. METHODS: In a 3-year period between January 2017 and December 2019, over 40,000 pregnant women underwent NIPT clinical screening test for fetal T21, T18, T13, SCA, and RCA in our laboratory. NIPT samples were processed using the NextSeq CN500 platform. The positive results were confirmed by karyotyping, and chromosomal microarray analysis (CMA) or copy number variants (CNV) sequencing. Details of the pregnancy outcomes were collected via telephone interview. RESULTS: NIPT results were available for 41,819 cases; 691 positive cases were reported. The overall sensitivity for detection of T21, T18, T13, SCA, and RCA was 99.21, 100.00, 100.00, 98.55, and 100.00%, and the specificity was 99.95, 99.94, 99.98, 99.69, and 99.92%, respectively. The positive predictive values (PPVs) for detection of T21, T18, T13, SCA, and RCA were 85.62, 45.24, 40.00, 34.17, and 13.51%, respectively, and those for detection of 45,X, 47,XXY, 47,XXX, 47,XYY, and 46,XY(delX) 20.00, 59.18, 28.95, 61.54, and 25.00%, respectively. Regarding pregnancy outcomes, 92.38% of the pregnancies with confirmed aneuploidies were terminated, and 91.20% of those identified as having a false-positive result were carried to term. Among 252 unconfirmed cases, 24.60% of the pregnancies were terminated and 38.10% carried to term, while 37.30% declined interview. CONCLUSIONS: NIPT is widely used to screen fetal aneuploidies based on its high sensitivity and specificity. However, in this study, the PPVs of NIPT in terms of detecting T18, T13, XO, XXX and RCA were < 50%. In addition, more than one-third of NIPT-positive women did not accept invasive prenatal diagnosis. Confirmatory diagnosis is strongly recommended for women with positive NIPT outcomes before any further decision is made.

Prognostic and clinicopathological values of LINC00665 in cancers: a systematic review and China population-based meta-analysis.

BACKGROUND: Recent studies have uncovered that the aberrant expression of LINC00665 contributes to the malignant pathological process of various cancers and is closely related to the unfavorable prognosis of patients with cancer. However, a systematic analysis of the prognostic and clinicopathologic values of LINC00665 in cancers has not been conducted. OBJECTIVE: We aim to clarify the association of LINC00665 expression with patient survival and clinicopathologic phenotypes in cancers. METHODS: An electronic search of PubMed, Embase and Web of Science was performed to select eligible literature. Pooled hazard ratio (HR) and odds ratio (OR) were calculated to assess the clinical importance of LINC00665. The fixed-effects model was used to analyze the combined HR values and 95% CI when the studies had no significant heterogeneity (P > 0.1 for the Chi-square test or I2 < 50%). Begg's test and sensitivity analysis were also conducted. This study was registered in The International Prospective Register of Systematic Reviews (PROSPERO registration number: CRD42021290123). RESULTS: A total of 710 patients from 10 eligible studies were enrolled in this meta-analysis, which was based on China population. The pooled results of this analysis revealed that high-level expression of LINC00665 was notably correlated with poor overall survival (HR = 2.08, 95% CI = 1.57-2.75) and recurrence-free survival (HR = 2.49, 95% CI = 1.63-3.80) in human cancers. Elevated LINC00665 expression was also correlated with more advanced clinical stage, earlier lymph node metastasis, lower tumor differentiation, earlier distant metastasis and larger tumor size. CONCLUSION: LINC00665 expression was critically related to the cancer prognosis, which has important prognostic implications for clinical prediction.

Prognostic Implication of a Cuproptosis-Related miRNA Signature in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most frequently diagnosed malignancies globally, accounting for the third cause of cancer mortality. Cuproptosis, a copper-induced cell death, was recently reported in Science. The purpose of this study was to evaluate the prognostic implication of cuproptosis-related miRNAs (CRMs) in HCC. Methods: Transcriptomic data and clinicopathological features of patients with HCC were extracted from the Cancer Genome Atlas (TCGA) database. Prognostic CRM signature was established by utilizing univariate Cox regression and LASSO analyses. To validate the accuracy of prediction, the Kaplan-Meier (K-M) and time-dependent receiver operating characteristic (ROC) analyses were adopted. A nomogram comprising clinical characteristics and the miRNA signature was developed to improve the prediction of patient outcomes. Finally, functional enrichment analysis and immune infiltration analysis were carried out. Results: Of CRMs, 14 were obtained to construct a prognostic miRNA signature. This CRM signature was an independent factor for predicting overall survival (OS). Kaplan-Meier curves demonstrated a noteworthy difference in survival rates between different risk subgroups (p < 0.001). The robust prognostic capacity of this signature was exhibited by sampling verification and stratified survival analysis. Functional analysis indicated that the high-risk group was mainly enriched in signaling pathways and different levels of immune infiltration were revealed between the two risk groups. The potential interaction of the model with the immune checkpoint activities was also detected. Conclusion: The CRM signature could act as an independent predictor to guide individual treatment strategies, which could provide fundamental insights for further studies.

Positive predictive value estimates for noninvasive prenatal testing from data of a prenatal diagnosis laboratory and literature review.

OBJECTIVE: Since 2011, noninvasive prenatal testing (NIPT) has undergone rapid expansion, with both utilization and coverage. However, conclusive data regarding the clinical validity and utility of this testing tool are lacking. Thus, there is a continued need to educate clinicians and patients about the current benefits and limitations in order to inform pre- and post-test counseling, pre/perinatal decision making, and medical risk assessment/management. METHODS: This retrospective study included women referred for invasive prenatal diagnosis to confirm positive NIPT results between January 2017 and December 2020. Prenatal diagnosis testing, including karyotyping, chromosomal microarray analysis (CMA) were performed. Positive predictive values (PPVs) were calculated. RESULTS: In total, 468 women were recruited. The PPVs for trisomies 21, 18, and 13 were 86.1%, 57.8%, and 25.0%, respectively. The PPVs for rare chromosomal abnormalities (RCAs) and copy number variants (CNVs) were 17.0% and 40.4%, respectively. The detection of sex chromosomal aneuploidies (SCAs) had a PPV of 20% for monosomy X, 23.5% for 47,XXX, 68.8% for 47,XXY, and 62.5% for 47,XYY. The high-risk groups had a significant increase in the number of true positive cases compared to the low- and moderate-risk groups. CONCLUSIONS: T13, monosomy X, and RCA were associated with lower PPVs. The improvement of cell-free fetal DNA screening technology and continued monitoring of its performance are important.

Leveraging Existing 16SrRNA Microbial Data to Define a Composite Biomarker for Autism Spectrum Disorder.

Cumulative studies have utilized high-throughput sequencing of the 16SrRNA gene to characterize the composition and structure of the microbiota in autism spectrum disorder (ASD). However, they do not always obtain consistent results; thus, conducting cross-study comparisons is necessary. This study sought to analyze the alteration of fecal microbiota and the diagnostic capabilities of gut microbiota biomarkers in individuals with ASD using the existing 16SrRNA microbial data and explore heterogeneity among studies. The raw sequence and metadata from 10 studies, including 1,019 samples, were reanalyzed. Results showed no significant difference in alpha diversity of fecal microbiota between ASD and the control group. However, a significant difference in the composition structure of fecal microbiota was observed. Given the large differences in sample selection and technical differences, the separation of fecal microbiota between ASD and controls was not observed. Subgroup analysis was performed on the basis of different country of origin, hypervariable regions, and sequencing platforms, and the dominant genera in ASD and healthy control groups were determined by linear discriminant analysis (LDA) of the effect size (LEfSe) algorithm and Wilcoxon rank-sum test. Machine learning analyses were carried out to determine the diagnostic capabilities of potential microbial biomarkers. A total of 12 genera were identified to distinguish ASD from control, and the AUC of the training set and verification set was 0.757 and 0.761, respectively. Despite cohort heterogeneity, gut microbial dysbiosis of ASD has been proven to be a widespread phenomenon. Therefore, fecal microbial markers are of great significance in diagnosing ASD diseases and possible candidates for further mechanistic study of the role of intestinal microbiota in ASD. IMPORTANCE This study provides an updated analysis to characterize the gut microbiota in ASD using 16SrRNA gene high-throughput sequencing data from 10 publicly available studies. Our analysis suggests an association between the fecal microbiota and ASD. Sample selection and technical differences between studies may interfere with the species composition analysis of the ASD group and control group. By summarizing the results of 16SrRNA gene sequencing from multiple fecal samples, we can provide evidence to support the use of microbial biomarkers to diagnose the occurrence of ASD. Our study provides a new perspective for further revealing the correlation between gut microbiota and ASD from the perspective of 16SrRNA sequencing in larger samples.

A Novel Angiogenesis-Related Prognostic Signature Associated with the Hepatocellular Carcinoma Immune Microenvironment and Survival Outcome.

PURPOSE: Hepatocellular carcinoma (HCC) is a highly vascularized solid tumor characterized by neovascularization and vascular invasion. Angiogenesis plays an essential role in the occurrence and development of liver cancer. Our study aimed to investigate the prognostic value of angiogenesis-related genes in liver cancer. PATIENTS AND METHODS: The transcriptome data and corresponding clinical information of patients with liver cancer were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. In the TCGA cohort, differential expression and prognostic analyses were used to screen angiogenesis-related candidate prognostic genes. We then used least absolute shrinkage and selection operator regression analysis to construct a prognostic signature using 10 angiogenesis-related prognostic genes. The reliability of the prognostic signature was assessed in the TCGA and ICGC cohorts. In addition, we comprehensively analyzed the correlation of the prognostic signature with the tumor microenvironment, chemotherapy drugs, and specific genes. RESULTS: We identified 37 angiogenesis-related differentially expressed genes that were remarkably associated with prognosis. Ten of these genes were used to establish a survival and prognostic signature. This signature can distinguish between high-risk and low-risk groups and performs well in overall survival prediction, as demonstrated by internal and external validations. In addition, we observed that the high-risk group was remarkably associated with immune infiltration in the tumor microenvironment and had a different sensitivity to chemotherapeutic agents compared with the low-risk group. Moreover, the high-risk population was positively correlated with the expression of several special genes, such as immune checkpoint-related genes. CONCLUSION: Our results demonstrated that prognostic signatures based on angiogenesis-related genes are involved in the development of HCC and may provide new insights into accurate clinical decision-making and therapeutic evaluation of patients with HCC.

Inflammatory biomarkers in older adults with frailty: a systematic review and meta-analysis of cross-sectional studies.

BACKGROUND: Systemic chronic inflammation has been proposed as an essential mediating factor in frailty, and several studies tested its relationship with frailty. However, the issue is still controversial. OBJECTIVES: We identified observational studies and pooled their results to assess whether abnormal expression of inflammatory biomarkers is present in the blood of older adults with frailty. METHODS: We conducted a systematic search on the Medline, Embase, and Web of Science database from inception to 1st September 2021. The quality of included studies was assessed using the JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies (JBI-MAStARI). Study heterogeneity was assessed with the Cochran Q test and I2 statistic. Pooled estimates were obtained through random-effect models. Sensitivity analyses were conducted by excluding one of the studies. Egger's regression test and observation of funnel plots were used to detect small-study effects and publication bias. PROSPERO registration: CRD42020172853. RESULT: A total of 53 cross-sectional studies corresponding to 56 independent study populations were included in this analysis. There were 31 study populations with three frailty categories (3144 frailty, 14,023 pre-frailty, 10,989 robust) and 25 study populations with two frailty categories (2576 frailty, 8368 non-frailty). This meta-analysis performed pooled analyses for the inflammatory biomarker leukocyte, lymphocytes, CRP, IL-6, IL-10, and TNF-α. Older adults with frailty had lower lymphocytes and higher interleukin-6 (IL-6), C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) levels compared with the control group. However, there was no significant difference in leukocyte and IL-10 levels in the two groups. CONCLUSIONS: These findings suggest that peripheral inflammatory biomarkers lymphocytes, IL-6, CRP, and TNF-α are related to frailty status. Our findings are not conclusive regarding the causal relationship between chronic inflammation and frailty, so the development of further longitudinal and well-designed studies focused on this is necessary.

Identification and Validation of the lncRNA BACE1-AS as Immune-Related Influencing Factor in Tumorigenesis following Pan-Carcinoma Analysis.

BACKGROUND: The lncRNA BACE1-AS was identified as a plasma molecular marker in the early diagnosis of Alzheimer's disease, but its role in tumors remains poorly defined. METHODS: The expression patterns, genomic mutation, and prognostic significance of BACE1-AS in pan-cancers were compared by analyzing 32 types of tumors from The Cancer Genome Atlas and cBioPortal databases. The relationships between BACE1-AS expression levels and the degree of immune cell infiltration, immune components, and immune-related genes were explored. The possible molecular mechanisms of BACE1-AS in tumors were explored using gene set enrichment analysis (GSEA). Finally, the role of BACE1-AS in hepatocellular carcinoma was confirmed via quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: BACE1-AS expression levels were significantly upregulated in LIHC, GBM, KIRC, CHOL, STAD, KICH, COAD, and PRAD. Higher expression levels of BACE1-AS were associated with worse overall survival in patients with HNSC and LIHC, while the opposite was found in PCPG and THCA. The overall mutation rate of BACE1-AS in pan-cancer was only approximately 0.9%, and it occurred mainly in uveal melanoma and uterine carcinoma. Generally, BACE1-AS expression was negatively correlated with the immune microenvironment. BACE1-AS expression was mainly related to naïve B cells, activated memory CD4 T cells, monocytes, M1 macrophages, M2 macrophages, and resting mast cells. The potential mechanisms of BACE1-AS in tumors were mainly via regulating the activities of B cell-mediated immunity, immune response regulating cell surface receptor signaling, RNA binding in posttranscriptional gene silencing, B cell receptor signaling pathways, and immune receptor activity. Finally, the qRT-PCR results confirmed that the expression levels of BACE1-AS in hepatocellular carcinoma cell lines were upregulated. CONCLUSIONS: Overall, our results suggest that BACE1-AS is associated with the expression, prognosis, and rate of immune cell infiltration of most tumors. Thus, BACE1-AS may be a potential target for immunotherapies aimed at improving cancer patient outcomes.

Non-Coding RNAs in Gastric Cancer: From Malignant Hallmarks to Clinical Applications.

Gastric cancer (GC) is one of the most lethal malignancies worldwide. However, the molecular mechanisms underlying gastric carcinogenesis remain largely unknown. Over the past decades, advances in RNA-sequencing techniques have greatly facilitated the identification of various non-coding RNAs (ncRNAs) in cancer cells, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Accumulating evidence has revealed that ncRNAs are essential regulators in GC occurrence and development. However, ncRNAs represent an emerging field of cancer research, and their complex functionality remains to be clarified. Considering the lack of viable biomarkers and therapeutic targets in GC, further studies should focus on elucidating the intricate relationships between ncRNAs and GC, which can be translated into clinical practice. In this review, we summarize recent research progress on how ncRNAs modulate the malignant hallmarks of GC, especially in tumor immune escape, drug resistance, and stemness. We also discuss the promising applications of ncRNAs as diagnostic biomarkers and therapeutic targets in GC, aiming to validate their practical value for clinical treatment.

A Novel Autophagy-Related lncRNA Prognostic Signature Associated with Immune Microenvironment and Survival Outcomes of Gastric Cancer Patients.

PURPOSE: Autophagy plays a crucial role in the initiation and progression of gastric cancer (GC). However, the role of autophagy-related lncRNAs in GC remains unknown. This study aimed to investigate the prognostic value of the autophagy-related lncRNA signature and its role in the tumor immune microenvironment (TIME) of GC. METHODS: RNA-sequencing (RNA-seq) and clinical data of GC patients were extracted from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analyses were performed to identify the autophagy-related lncRNA prognostic signature which was validated in the test set and entire set. The survival and predictive performance were analyzed based on the Kaplan-Meier and ROC curves. Furthermore, the CIBERSORT algorithm was applied to explore the relationship between this signature and the immune cell infiltration. To elucidate the potential functions of autophagy-related lncRNAs in GC, we constructed the lncRNA-mRNA co-expression network and performed enrichment analysis. Principal component analysis (PCA) and Gene Set Enrichment Analysis (GSEA) were further performed to compare the different statuses between the high-risk and low-risk groups. RESULTS: We identified 5 autophagy-related lncRNAs (AL355574.1, AC010768.2, AP000695.2, AC087286.2, and HAGLR) to construct a prognostic signature. This signature could be an independent prognostic indicator for GC patients and had a higher prediction efficiency than other clinicopathological parameters. Furthermore, patients in the high-risk score group had a stronger immunosuppressive microenvironment than the low-risk group. The enrichment analysis for mRNAs co-expressed with these lncRNAs indicated that autophagy-related signaling pathways were remarkably enriched. PCA and GSEA further revealed different autophagy and immune statuses in the high- and low-risk groups. CONCLUSION: The 5 autophagy-related lncRNA signature has significant clinical implications in prognosis prediction of GC. Meanwhile, our study elucidates the critical role of the autophagy-related lncRNA signature in the TIME of GC.

Altered Fecal Microbiota Composition in Older Adults With Frailty.

Objective: Frailty is a common geriatric syndrome that is diagnosed and staged based mainly on symptoms. We aimed to evaluate frailty-related alterations of the intestinal permeability and profile fecal microbiota of healthy and frail older adults to identify microbial biomarkers of this syndrome. Methods: We collected serum and fecal samples from 94 community-dwelling older adults, along with anthropometric, medical, mental health, and lifestyle data. Serum inflammatory cytokines IL-6 and HGMB1 and the intestinal permeability biomarker zonulin were measured using enzyme-linked immunosorbent assays. The 16S rRNA amplicon sequencing method was performed to determine the fecal composition of fecal microbiota. We analyzed the diversity and composition differences of the gut microbiota in the two groups and assessed the relationship between the changes in microbiota structure and clinical biomarkers. Results: Older adults with frailty showed higher concentrations of IL-6, HGMB1, and zonulin. Although there were no statistically significant differences in the diversity index and evenness indices or species richness of fecal microbiota between the two groups, we found significant microbiota structure differences. Compared with the control group, fecal samples from the frail group had higher levels of Akkermansia, Parabacteroides, and Klebsiella and lower levels of the commensal genera Faecalibacterium, Prevotella, Roseburia, Megamonas, and Blautia. Spearman's correlation analysis showed that the intergenus interactions were more common in healthy controls than older adults with frailty. Escherichia/Shigella, Pyramidobacter, Alistipes, and Akkermansia were positively correlated with IL-6, while Faecalibacterium, Prevotella, and Roseburia were negatively correlated with IL-6. Alistipes were found to be positively correlated with HGMB1. Akkermansia and Alistipes were linked to the increased serum level of inflammatory factors and intestinal permeability. Conclusions: Frailty is associated with differences in the composition of fecal microbiota. These findings might aid in the development of probiotics or microbial-based therapies for frailty.