Genetic risk, adherence to healthy lifestyle behaviors, and risk of cholelithiasis: A population-based cohort study.

OBJECTIVE: Genetic and lifestyles contribute to cholelithiasis, but the impact of adhering to healthy lifestyle on cholelithiasis risk remains uncertain. We aimed to assess combined lifestyle factors and a polygenic risk score on incident cholelithiasis. METHODS: We utilized cholelithiasis genome-wide association study (GWAS) data from FinnGen study, constructing varied polygenic risk score (PRS), and applied them to 317,640 UK Biobank participants. The relative and absolute risk of incident cholelithiasis associated with six well-established lifestyle risk factors, was evaluated and stratified by PRS (low risk [quintile 1], intermediate risk [quintiles 2-4] and high risk [quintile 5]). Lifestyle score was also categorized into favorable, intermediate, and unfavorable groups. RESULTS: The PRS derived from 13 single nucleotide polymorphisms (p ≤ 5 × 10-6, r2 < 0.001) showed the best performance. A significant gradient of increase in risk of cholelithiasis was observed across the quintiles of the polygenic risk score (p < 0.001). Compared to participants with low genetic risk, those with intermediate or high genetic risk had a 10% (95% confidence interval [CI] = 1.05-1.17) and 24% (95% CI = 1.16-1.32) higher risk of cholelithiasis. An unfavorable lifestyle was associated with an approximately 50% higher risk of cholelithiasis than a favorable lifestyle. Participants with high genetic risk and an unfavorable lifestyle had 98% (Hazard ratio [HR]: 1.98; 95% CI: 1.67-2.35) higher risk of cholelithiasis than those with low genetic risk and a favorable lifestyle. CONCLUSIONS: Our study highlights the importance of lifestyle behaviors intervention on cholelithiasis risk regardless of the genetic risk in White European population.

A High-Voltage Cathode Material with Ultralong Cycle Performance for Sodium-Ion Batteries.

Vanadium-based polyanionic materials are promising electrode materials for sodium-ion batteries (SIBs) due to their outstanding advantages such as high voltage, acceptable specific capacity, excellent structural reversibility, good thermal stability, etc. Polyanionic compounds, moreover, can exhibit excellent multiplicity performance as well as good cycling stability after well-designed carbon covering and bulk-phase doping and thus have attracted the attention of multiple researchers in recent years. In this paper, after the modification of carbon capping and bulk-phase nitrogen doping, compared to pristine Na3 V2 (PO4 )3 , the well optimized Na3 V(PO3 )3 N/C possesses improved electromagnetic induction strength and structural stability, therefore exhibits exceptional cycling capability of 96.11% after 500 cycles at 2 C (1 C = 80 mA g-1 ) with an elevated voltage platform of 4 V (vs Na+ /Na). Meanwhile, the designed Na3 V(PO3 )3 N/C possesses an exceptionally low volume change of ≈0.12% during cycling, demonstrating its quasi-zero strain property, ensuring an impressive capacity retention of 70.26% after 10,000 cycles at 2 C. This work provides a facial and cost-effective synthesis method to obtain stable vanadium-based phosphate materials and highlights the enhanced electrochemical properties through the strategy of carbon rapping and bulk-phase nitrogen doping.

Circular RNAs in pancreatic cancer progression.

Pancreatic cancer (PC), typically diagnosed at relatively advanced stages with poor prognosis, is a dominant cause of cancer-related deaths worldwide. Accumulating evidence demonstrates that circular RNAs (circRNAs) are abnormally expressed in diverse tumors and affect tumorigenesis and progression. In this article, we examine the roles of circRNAs in regulation of PC progression. Additionally, circRNAs enriched in exosomes could be transferred among PC cells to modulate malignancy. Characterization of regulatory mechanisms involving circRNAs in general and PC specifically will enable earlier detection and potential development of therapeutic strategies.

Non-Coding RNA in Cholangiocarcinoma: An Update.

Cholangiocarcinoma (CCA) is one of the most common tumors with high malignancy. Its incidence is increasing year by year, and it is insidious and easily metastasized, and most patients are already in advanced stages when they are diagnosed. Surgery is an essential treatment for CCA, but the 5-year survival rate is still unsatisfactory due to the low early diagnosis rate and high malignancy of CCA. Therefore, exploring the molecular mechanisms of CCA to find reliable biomarkers and effective therapeutic targets is essential to improve the early diagnosis and survival rate of CCA. Non-coding RNA (ncRNA) is a class of RNA without protein-coding ability, mainly including microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). In recent years, numerous pieces of evidence have shown that aberrantly expressed ncRNAs can regulate the occurrence and development of CCA through various mechanisms such as mediating epigenetic, sponge miRNAs regulating the expression of target genes and participating in regulating cancer-related signaling pathways, which provides new approaches and ideas for early diagnosis, prognosis assessment and therapeutic targeting of CCA. In this paper, we review the molecular mechanisms of lncRNAs and circRNAs regulating the progression of CCA in recent years and discuss their potential clinical value in CCA.

Recent advances on low-Co and Co-free high entropy layered oxide cathodes for lithium-ion batteries.

As the price of the precious metal cobalt continues to rise, there is an urgent need for a cobalt-free or low-cobalt electrode material to reduce the cost of lithium-ion batteries, which are widely used commercially, while maintaining their performance as much as possible. With the introduction of the new concept of high entropy (HE) materials into the battery field, low cobalt and cobalt free HE novel lithium-ion batteries have attracted great attention. It possesses important research value to use HE materials to reduce the use of cobalt metal in electrode materials. In this perspective, the comparison between the new cathode materials of low cobalt and cobalt-free HE lithium-ion battery and traditional cathode materials and the latest progress in maintaining structural stability and conductivity are introduced. It is believed that low cobalt and cobalt-free and HE layered oxides can be used to replace the function of cobalt in the cathode materials of lithium-ion batteries. Finally, the future research directions and the synthesis method of HE cathode materials for lithium-ion batteries are also discussed.

Little things with significant impact: miRNAs in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has developed into one of the most lethal, aggressive, and malignant cancers worldwide. Although HCC treatment has improved in recent years, the incidence and lethality of HCC continue to increase yearly. Therefore, an in-depth study of the pathogenesis of HCC and the search for more reliable therapeutic targets are crucial to improving the survival quality of HCC patients. Currently, miRNAs have become one of the hotspots in life science research, which are widely present in living organisms and are non-coding RNAs involved in regulating gene expression. MiRNAs exert their biological roles by suppressing the expression of downstream genes and are engaged in various HCC-related processes, including proliferation, apoptosis, invasion, and metastasis. In addition, the expression status of miRNAs is related to the drug resistance mechanism of HCC, which has important implications for the systemic treatment of HCC. This paper reviews the regulatory role of miRNAs in the pathogenesis of HCC and the clinical applications of miRNAs in HCC in recent years.

Extra cup of tea intake associated with increased risk of Alzheimer's disease: Genetic insights from Mendelian randomization.

Background: Observational studies report inconclusive effects of tea consumption on the risk of Alzheimer's disease (AD), and the mechanisms are unclear. This study aims to investigate the effects of genetically predicted tea intake (cups of tea consumed per day) on AD, brain volume, and cerebral small vessel disease (CSVD) using the two-sample Mendelian randomization (MR) method. Methods: Summary statistics of tea intake were obtained from UK Biobank (N = 447,485), and AD was from the International Genomics of Alzheimer's Project (N = 54,162). Genetic instruments were retrieved from UK Biobank using brain imaging-derived phenotypes for brain volume outcomes (N > 33,224) and genome-wide association studies for CSVD (N: 17,663-48,454). Results: In the primary MR analysis, tea intake significantly increased the risk of AD using two different methods (ORIVW = 1.48, 95% CI: [1.14, 1.93]; ORWM = 2.00, 95% CI: [1.26, 3.18]) and reached a weak significant level using MR-Egger regression (p < 0.1). The result passed all the sensitivity analyses, including heterogeneity, pleiotropy, and outlier tests. In the secondary MR analysis, per extra cup of tea significantly decreased gray matter (ßWM = -1.63, 95% CI: [-2.41, -0.85]) and right hippocampus volume (ßWM = -1.78, 95% CI: [-2.76, -0.79]). We found a nonlinear association between tea intake and AD in association analysis, which suggested that over-drinking with more than 13 cups per day might be a risk factor for AD. Association analysis results were consistent with MR results. Conclusion: This study revealed a potential causal association between per extra cup of tea and an increased risk of AD. Genetically predicted tea intake was associated with a decreased brain volume of gray matter and the right hippocampus, which indicates that over-drinking tea might lead to a decline in language and memory functions. Our results shed light on a novel possible mechanism of tea intake to increase the risk of AD by reducing brain volume.

Long noncoding RNA HAND2-AS1: A crucial regulator of malignancy.

Long non-coding RNAs (LncRNAs) are single-stranded RNAs over 200 nucleotides in length that have no protein-coding function and have long been considered non-functional by-products of transcription. Recent studies have shown that dysregulation of lncRNAs may be involved in the malignant biological behavior of tumors. Targeted regulation of lncRNAs has become a research focus of anti-tumor treatment. LncRNAs heart and neural crest derivatives expressed 2 antisense RNA 1 (HAND2-AS1) was down-regulated in various tumors and can be used as a critical tumor regulator to modulate tumor cells proliferation, apoptosis, metastasis, invasion, metabolism and drug resistance. Additionally, aberrantly expressed HAND2-AS1 was closely related to the clinical pathological characteristics of cancer patients and serve as a promising tumor diagnostic and prognostic biomarker. This article aims to review the roles of HAND2-AS1 in tumorigenesis and development, as well as the underlying molecular mechanisms and clinical significance.

Maximizing energy utilization in DMD-based projection lithography.

In digital micromirror device (DMD)-based projection photolithography, the throughput largely depends on the effectiveness of the laser energy utilization, which is directly correlated to the diffraction efficiency of DMD. Here, to optimize the DMD diffraction efficiency and thus the laser energy utilization, we calculate the diffraction efficiencies Ediffraction of DMD with various pitch sizes at wavelengths ranging from 200 nm to 800 nm, using the two-dimensional blazed grating diffraction theory. Specifically, the light incident angle is optimized for 343 nm laser and 7.56 µm pitch-size DMD, and the maximum single-order diffraction efficiency Ediffraction is increased from 40% to 96%. Experimentally, we use the effective energy utilization ηeff = Ediffraction,(m,n)/Σ[Ediffraction,(m,n)] at the entrance pupil plane of the objective to verify the effectiveness of the optimized illumination angle in a lithography illumination system with parallel beams of two wavelengths (343 nm and 515 nm). The ηeff of a "blaze" order at a 34° angle of incidence can be optimized up to 88%. The experimental results are consistent with the tendency of the calculated results, indicating that this optimization model can be used to improve the energy utilization of projection lithography with the arbitrarily designable wavelengths and the DMD's pitch size.