Immune surveillance of brain metastatic cancer cells is mediated by IFITM1.

Brain metastasis, most commonly originating from lung cancer, increases cancer morbidity and mortality. Although metastatic colonization is the rate-limiting and most complex step of the metastatic cascade, the underlying mechanisms are poorly understood. Here, in vivo genome-wide CRISPR-Cas9 screening revealed that loss of interferon-induced transmembrane protein 1 (IFITM1) promotes brain colonization of human lung cancer cells. Incipient brain metastatic cancer cells with high expression of IFITM1 secrete microglia-activating complement component 3 and enhance the cytolytic activity of CD8+ T cells by increasing the expression and membrane localization of major histocompatibility complex class I. After activation, microglia (of the innate immune system) and cytotoxic CD8+ T lymphocytes (of the adaptive immune system) were found to jointly eliminate cancer cells by releasing interferon-gamma and inducing phagocytosis and T-cell-mediated killing. In human cancer clinical trials, immune checkpoint blockade therapy response was significantly correlated with IFITM1 expression, and IFITM1 enhanced the brain metastasis suppression efficacy of PD-1 blockade in mice. Our results exemplify a novel mechanism through which metastatic cancer cells overcome the innate and adaptive immune responses to colonize the brain, and suggest that a combination therapy increasing IFITM1 expression in metastatic cells with PD-1 blockade may be a promising strategy to reduce metastasis.

Endoscopic submucosal dissection for early cancers or precancerous lesions of the upper GI tract in cirrhotic patients with esophagogastric varices: 10-year experience from a large tertiary center in China.

BACKGROUND AND AIMS: Treatment strategies for early cancers or precancerous lesions of the upper GI tract in patients with cirrhosis and esophagogastric varices (EGVs) are complicated and risky. The aim of this study was to assess the efficacy and safety of endoscopic submucosal dissection (ESD) in the treatment of such patients and explore optimal treatment strategies. METHODS: We retrospectively enrolled 15 patients with cirrhosis and EGV who underwent ESD for early cancers or precancerous lesions of the upper GI tract from January 2012 to December 2021 at our center. Clinical features, endoscopic findings, treatment methods, adverse events, and follow-up data were analyzed. RESULTS: Of the 15 patients, 1 had a platelet count <30 × 1000/mm3. Five were untreated for EGV, 1 was treated after ESD, 6 were treated before ESD, 1 was treated before and during ESD, and 2 were treated during ESD. The R0 resection rate was 100%. Of the 16 mucosal lesions, 15 were endoscopic resection bleeding (ERB)-0 or ERB-c1, and 1 was ERB-c2. No patient experienced deterioration in liver function. The only adverse events were fever in 2 patients and postoperative bleeding in 2 patients. During a median follow-up of 27 months, 1 patient's esophageal high-grade dysplasia recurred at 19 months. No death resulted from the ESD procedure, liver function injury, or GI tumor itself. CONCLUSIONS: ESD is an effective and safe treatment for early cancers or precancerous lesions of the upper GI tract in patients with cirrhosis and EGV. The incidence of severe adverse events is very low due to the development of individualized clinical treatment strategies.

Developmental eye movement strategies for decoding facial expressions of emotion.

In our daily lives, we routinely look at the faces of others to try to understand how they are feeling. Few studies have examined the perceptual strategies that are used to recognize facial expressions of emotion, and none have attempted to isolate visual information use with eye movements throughout development. Therefore, we recorded the eye movements of children from 5 years of age up to adulthood during recognition of the six "basic emotions" to investigate when perceptual strategies for emotion recognition become mature (i.e., most adult-like). Using iMap4, we identified the eye movement fixation patterns for recognition of the six emotions across age groups in natural viewing and gaze-contingent (i.e., expanding spotlight) conditions. While univariate analyses failed to reveal significant differences in fixation patterns, more sensitive multivariate distance analyses revealed a U-shaped developmental trajectory with the eye movement strategies of the 17- to 18-year-old group most similar to adults for all expressions. A developmental dip in strategy similarity was found for each emotional expression revealing which age group had the most distinct eye movement strategy from the adult group: the 13- to 14-year-olds for sadness recognition; the 11- to 12-year-olds for fear, anger, surprise, and disgust; and the 7- to 8-year-olds for happiness. Recognition performance for happy, angry, and sad expressions did not differ significantly across age groups, but the eye movement strategies for these expressions diverged for each group. Therefore, a unique strategy was not a prerequisite for optimal recognition performance for these expressions. Our data provide novel insights into the developmental trajectories underlying facial expression recognition, a critical ability for adaptive social relations.

Genome sequencing demonstrates high diagnostic yield in children with undiagnosed global developmental delay/intellectual disability: A prospective study.

Genome sequencing (GS) has been used in the diagnosis of global developmental delay (GDD)/intellectual disability (ID). However, the performance of GS in patients with inconclusive results from chromosomal microarray analysis (CMA) and exome sequencing (ES) is unknown. We recruited 100 pediatric GDD/ID patients from multiple sites in China from February 2018 to August 2020 for GS. Patients have received at least one genomic diagnostic test before enrollment. Reanalysis of their CMA/ES data was performed. The yield of GS was calculated and explanations for missed diagnoses by CMA/ES were investigated. Clinical utility was assessed by interviewing the parents by phone. The overall diagnostic yield of GS was 21%. Seven cases could have been solved with reanalysis of ES data. Thirteen families were missed by previous CMA/ES due to improper methodology. Two remained unsolved after ES reanalysis due to complex variants missed by ES, and a CNV in untranslated regions. Follow-up of the diagnosed families revealed that nine families experienced changes in clinical management, including identification of targeted treatments, cessation of unnecessary treatment, and considerations for family planning. GS demonstrated high diagnostic yield and clinical utility in this undiagnosed GDD/ID cohort, detecting a wide range of variant types of different sizes in a single workflow.

Comprehensive Analysis of Congenital Adrenal Hyperplasia Using Long-Read Sequencing.

BACKGROUND: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder that has been included in newborn screening programs. Current approaches to gene testing for CAH are facing challenges because of the complexity of the CYP21A2 locus and genetic heterogeneity of the disease. METHODS: A comprehensive analysis of CAH (CACAH) combining long-range locus-specific PCR and long-read sequencing (LRS) was developed to perform full sequence analysis of 5 common CAH candidate genes, including CYP21A2, CYP11B1, CYP17A1, HSD3B2, and StAR. In a blind retrospective study, the clinical utility of CACAH was evaluated in 37 samples by comparing to standard CAH testing using multiplex ligation-dependent probe amplification (MLPA) plus Sanger sequencing. RESULTS: Of the 37 clinical samples, a total of 69 pathogenic variants were identified, comprising 65 CYP21A2 variants, 2 HSD3B2 variants, and 2 CYP17A1 variants. For CYP21A2, the most frequent variant was c.518T > A (29.2%), followed by c.293-13C/A > G (21.5%). Compared with the current CAH testing using MLPA plus Sanger sequencing, the CACAH assay showed 100% specificity and 100% sensitivity, and precisely determined the junction sites of deletions/insertions and cis-trans configuration of multiple variants without analyzing family samples. Moreover, CACAH identified a case carrying 2 copies of CYP21A1 with the c.1451_1452delinsC variant on the same chromosome, which was not confirmed by MLPA plus Sanger sequencing. CONCLUSION: LRS-based CACAH can determine all genotypes of CAH accurately and reliably in one assay, presenting a comprehensive approach for CAH genetic diagnosis and carrier screening.

Comprehensive Analysis of Fragile X Syndrome: Full Characterization of the FMR1 Locus by Long-Read Sequencing.

BACKGROUND: Fragile X syndrome (FXS) is the most frequent cause of inherited X-linked intellectual disability. Conventional FXS genetic testing methods mainly focus on FMR1 CGG expansions and fail to identify AGG interruptions, rare intragenic variants, and large gene deletions. METHODS: A long-range PCR and long-read sequencing-based assay termed comprehensive analysis of FXS (CAFXS) was developed and evaluated in Coriell and clinical samples by comparing to Southern blot analysis and triplet repeat-primed PCR (TP-PCR). RESULTS: CAFXS accurately detected the number of CGG repeats in the range of 93 to at least 940 with mass fraction of 0.5% to 1% in the background of normal alleles, which was 2-4-fold analytically more sensitive than TP-PCR. All categories of mutations detected by control methods, including full mutations in 30 samples, were identified by CAFXS for all 62 clinical samples. CAFXS accurately determined AGG interruptions in all 133 alleles identified, even in mosaic alleles. CAFXS successfully identified 2 rare intragenic variants including the c.879A > C variant in exon 9 and a 697-bp microdeletion flanking upstream of CGG repeats, which disrupted primer annealing in TP-PCR assay. In addition, CAFXS directly determined the breakpoints of a 237.1-kb deletion and a 774.0-kb deletion encompassing the entire FMR1 gene in 2 samples. CONCLUSIONS: Long-read sequencing-based CAFXS represents a comprehensive assay for identifying FMR1 CGG expansions, AGG interruptions, rare intragenic variants, and large gene deletions, which greatly improves the genetic screening and diagnosis for FXS.

Influence of the type of carrier on ferromagnetism in a Si semiconductor implanted with Cu ions.

Silicon semiconductor samples implanted with Cu ions and samples co-implanted with Cu- and N-ions were prepared by MEVVA and the Kaufman technique. None of the samples showed evidence of secondary phases. The initially n-type Si matrix, when implanted with Cu ions, changed to a p-type semiconductor, and the Cu ions existed as local Cu2+ cations in the p-type environment. As a result, none of the Cu-implanted samples were ferromagnetic at room temperature. The co-implanted samples, on the other hand, showed room-temperature ferromagnetism because the introduction of N ions made the carrier type change from p-type to n-type which is favorable for the appearance of Cu2+. First principles calculations were applied to understand the experimental phenomena. The formation energy was reduced by implanting N ions, and was decreased effectively with the increase in ratio of N to Cu ions. The density of states and spin density of states indicated that the hybridization of s, p and d electrons induced ferromagnetism at 0 K. Particularly, we proposed possible exchange interactions between the Cu2+-N-(N4+)-Cu2+ ions to explain the ferromagnetism mechanism.

Pressure and Temperature Dependencies of Rate Coefficients for the Reaction OH + NO2 + M → Products.

The OH + NO2 reaction is a critically important process for radical chain termination in the atmosphere with a major impact on the ozone budgets of the troposphere and stratosphere. Rate constants for the reaction of OH + NO2 + M → products have been measured under conditions relevant to the upper troposphere/lower stratosphere with a laser photolysis-laser-induced fluorescence (LP-LIF) technique augmented by in situ optical spectroscopy for quantification of [NO2]. The experiments are carried out over the temperature range of 230-293 K and the pressure range 50-750 Torr of N2 and air and as a function of [O2]. The observed rate coefficients in N2 agree with the newest experimental literature data sets and are within experimental uncertainty of current recommended literature values at 293 K but are systematically higher by up to 22% at 700 Torr and 230 K. The efficacy of different falloff parametrizations has been examined and compared to those in literature sources. The collisional quenching efficiency of O2 was found to be in excellent agreement with current literature sources, and rate coefficients determined in air at 293 and 245 K were observed to be within uncertainty of the rate coefficients measured in N2 bath gas. This work has improved confidence in the literature rate coefficients under conditions of the lower troposphere (∼760 Torr, 280-310 K) toward the stratosphere (10-100 Torr, 220-250 K).

Clinical utility of noninvasive prenatal screening for expanded chromosome disease syndromes.

PURPOSE: To assess the clinical performance of an expanded noninvasive prenatal screening (NIPS) test ("NIPS-Plus") for detection of both aneuploidy and genome-wide microdeletion/microduplication syndromes (MMS). METHODS: A total of 94,085 women with a singleton pregnancy were prospectively enrolled in the study. The cell-free plasma DNA was directly sequenced without intermediate amplification and fetal abnormalities identified using an improved copy-number variation (CNV) calling algorithm. RESULTS: A total of 1128 pregnancies (1.2%) were scored positive for clinically significant fetal chromosome abnormalities. This comprised 965 aneuploidies (1.026%) and 163 (0.174%) MMS. From follow-up tests, the positive predictive values (PPVs) for T21, T18, T13, rare trisomies, and sex chromosome aneuploidies were calculated as 95%, 82%, 46%, 29%, and 47%, respectively. For known MMS (n = 32), PPVs were 93% (DiGeorge), 68% (22q11.22 microduplication), 75% (Prader-Willi/Angleman), and 50% (Cri du Chat). For the remaining genome-wide MMS (n = 88), combined PPVs were 32% (CNVs ≥10 Mb) and 19% (CNVs <10 Mb). CONCLUSION: NIPS-Plus yielded high PPVs for common aneuploidies and DiGeorge syndrome, and moderate PPVs for other MMS. Our results present compelling evidence that NIPS-Plus can be used as a first-tier pregnancy screening method to improve detection rates of clinically significant fetal chromosome abnormalities.

Reaction kinetics of OH + HNO3 under conditions relevant to the upper troposphere/lower stratosphere.

The OH initiated oxidation of HNO3 in the UT/LS plays an important role in controlling the O3 budget, removing HOx radicals whilst driving NOx/y partitioning chemistry by yielding NO3 radicals: OH + HNO3 → H2O + NO3. In this paper, k1(T, P) was measured using OH (A ← X) Laser Induced Fluorescence (LIF) and the data was modelled over the 223-298 K temperature and 25-750 Torr pressure ranges, using the modified Lindemann-Hinshelwood expression , where k0 = 5.2 × 10-14 exp(200/T) cm3 s-1, k2 = 8.4 × 10-17 exp(1900/T) cm3 s-1 and k3 = 1.6 × 10-34 exp(1745/T) cm3 s-1. A significant source of experimental uncertainty derives from accurate determination of HNO3 concentration, which is impacted by heterogeneous uptake of the low volatility HNO3 onto cold surfaces of the reactors. Our results represent the determination of k1(T, P) using two different in situ [HNO3] measurements: VUV absorption and a new two photon Photolysis Induced Fluoresence (PIF). Experimental results are discussed along with a computational master equation calculation (MESMER), which highlight the need for further theoretical study into the OH + HNO3 mechanism and potential energy surface. The atmospheric impact of these new rate constants were modelled using the STOCHEM-CRI chemistry transport global model, which have shown a small reduction in global budgets of key atmospheric species, with more significant changes in the NOx/HNO3 ratio, peaking in the tropical upper troposphere regions.

Compositional phase diagram and microscopic mechanism of Ba1-xCaxZryTi1-yO3 relaxor ferroelectrics.

With extensive first-principles density-functional calculations, we construct a three-dimensional compositional phase diagram of Ba1-xCaxZryTi1-yO3 (BCZT) with the Ca and Zr content in the ranges of 0 ≤ xCa ≤ 0.2 and 0 ≤ yZr ≤ 1. Our calculations show that, when the Zr content increases, the difference in energy and difference in the structural parameters of the cubic, tetragonal, orthorhombic, and rhombohedral phases of BCZT are reduced. Eventually, all four phases merge into a multiphase with coexisting cubic structures (MPCCS) under Zr-rich conditions, indicating that BCZT undergoes phase transition from a normal ferroelectric (NFE) to a relaxor ferroelectric (RFE), consistent with experimental observations. The 3D diagram shows that the regions of merged and separated energy surfaces correspond to the regions of the RFE and NFE, respectively, which suggests that a MPCCS corresponds to a RFE. In addition, with the MPCCS model and Landau-Devonshire theory, we provide an interpretation of the high electromechanical properties of the BCZT relaxor ferroelectric and apply it to the classical local random field and micro-macro domain transition models.

Identification of a fish specific chemokine CXCL_F2 in large yellow croaker (Larimichthys crocea) reveals its primitive chemotactic function.

Chemokines are a superfamily of cytokines regulating immune cell migration under both inflammatory and normal physiological conditions. Currently, a number of fish specific CXC chemokines, named as CXCL_F1-5, have been identified in several species. However, understanding of their functional characteristics is still limited. In this study, we identified a fish specific chemokine CXCL_F2 (LycCXCL_F2) from large yellow croaker (Larimichthys crocea). The open reading frame (ORF) of LycCXCL_F2 is 348 nucleotides long, encoding a protein of 115 amino acids (aa). The deduced LycCXCL_F2 protein contains a 20-aa signal peptide and a 95-aa mature polypeptide. Phylogenetic analysis showed that LycCXCL_F2 fell into a major clade formed by CXCL_F2 sequences and was separated from CXCL_F1 and CXCL_F3-5 subgroups. LycCXCL_F2 mRNA transcript was constitutively expressed in various tissues, with the highest levels in spleen and head kidney. After stimulation with inactivated trivalent bacterial vaccines, LycCXCL_F2 mRNA transcription was significantly increased in both spleen and head kidney. Moreover, recombinant LycCXCL_F2 protein exhibited obvious chemotaxis to monocytes, lymphocytes and eosnophils of PBLs isolated from large yellow croaker, but could not induce the respiratory burst of macrophages. These results indicate that this fish specific CXC chemokine LycCXCL_F2 possesses primitive chemotactic activity and may play a role in immune response in large yellow croaker.

Laser Measurements of the H Atom + Ozone Rate Constant at Mesospheric Temperatures.

The exothermic H + O3 reaction produces OH(v) Meinel band emissions, used to derive mesospheric H concentrations and chemical heating rates. We remeasured its rate constant to reduce its uncertainty and extended the measurements to lower mesospheric temperatures using modern laser-induced fluorescence (LIF) techniques. H atoms were produced by pulsed ultraviolet laser trace photolysis of O3, followed by reaction of O((1)D) with added H2. A second, delayed, frequency-mixed dye laser measured the reaction decay rate with the remaining ozone using LIF. We monitored either the H atom decay by two photon excitation at 205 nm and detection of red fluorescence, or the OH (v = 9) product time evolution with excitation of the B(2)Σ(+)-X(2)Π (0,9) band at 237 nm and emission in the blue B(2)Σ(+)-A(2)Σ(+) (0,7) band. By cooling the enclosed low pressure flow cell we obtained measurements from 140 to 305 K at 20 to 200 Torr in Ar. Small kinetic modeling corrections were made for secondary regeneration of H atoms. The results are consistent with the current NASA JPL recommendation for this rate constant and establish its extrapolation down to the lower temperatures of the mesosphere.

Rate Constant for the OH + CO Reaction at Low Temperatures.

Rate constants for the reaction of OH + CO → products (1) have been measured using laser photolysis/laser-induced fluorescence (LP/LIF) over the temperature range 193­296 K and at pressures of 50­700 Torr of Ar and N2. The reaction was studied under pseudo-first-order conditions, monitoring the decay of OH in the presence of a large excess of CO. The rate constants can be expressed as a combination of bimolecular and termolecular components. The bimolecular component was found to be temperature-independent with an expression given by kbi(T) = (1.54 ± 0.14) × 10(­13)[e(­(13±17)/T)] cm(3) molecule(­1) s(­1), with an error of one standard deviation. The termolecular component was fitted to the expression, kter = k0(T)[M]/[1 + (k0(T)[M]/k∞(T)] × 0.6({1+[log10(k0(T)[M]/k∞(T))]2}−1) where k0(T) = k0(300)(T/300)(−n) and k∞(T) = k∞(300)(T/300)(−m). The parameters for k0(T) were determined to be k0(300) = (6.0±0.5) × 10(−33) cm(6) molecule(­2) s(­1) in N2 and k0(300) = (3.4 ± 0.3) × 10(­33) cm(6) molecule(­2) s(­1) in Ar, with n = 1.9±0.5 and 2.0±0.4 in N2 and Ar, respectively. These parameters were determined using k0(T) and m from the NASA kinetics data evaluation (JPL Publication No. 10-6) since the experimental pressure range was far from the high-pressure limit. Addition of low concentrations of O2 had no discernible effect on the mechanism of the OH + CO reaction but resulted in secondary reactions which regenerated OH.

Atmospheric peroxy radical measurements using dual-channel chemical amplification cavity ringdown spectroscopy.

Peroxy (HO2 and RO2) radicals are important intermediates in tropospheric oxidation of hydrocarbons, and their accurate atmospheric measurements remain challenging. In this work, the peroxy radical chemical amplification (PERCA) method was combined with cavity ringdown spectroscopy (CRDS) to develop a dual-channel instrument for measurements of atmospheric peroxy radicals. In the amplification channel, the peroxy radicals were converted in an excess amount of NO and CO into a higher level of NO2 and measured along with the background NO2, while in the reference channel, only the background NO2 (ambient NO2 and NO2 converted from O3 reaction with NO) was monitored. The NO2 levels from both channels were measured simultaneously at a high time resolution (~1 s) using two identical CRDS systems with one 408.5-nm diode laser, and their difference gave the amplified NO2 from PERCA. The peroxy radical concentration was obtained from the amplified NO2 and the calibrated amplification factor or chain length (CL). The optimized CL was 190 ± 20 (1σ) using laboratory-generated HO2 and CH3O2 radical sources. The detection sensitivity was 4 ppt/10 s (3σ). Ambient measurements in Riverside, CA were carried out. This dual-channel diode-laser PERCA-CRDS instrument was compact and capable of providing real-time, in situ, and sensitive measurements of atmospheric peroxy radicals with fast time response.

Increased FAT10 expression is related to poor prognosis in pancreatic ductal adenocarcinoma.

It has been reported that FAT10 plays an important role in cell proliferation. Their activity is increased in malignant cells compared to benign cells. However, the clinical and functional significance of FAT10 expression has not been characterized previously in pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to assess FAT10 expression and to explore its contribution to PDAC. Real-time quantitative PCR was performed to examine FAT10 expression in 38 pairs of fresh frozen PDAC tissues and corresponding noncancerous tissues. Using immunohistochemistry, we performed a retrospective study of the FAT10 expression levels on 134 archival PDAC paraffin-embedded samples. The relationship between FAT10 mRNA expression and clinicopathological features was analyzed by appropriate statistics. Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the correlation between FAT10 expression and prognosis of PDAC patients. The relative mRNA expression of FAT10 was significantly higher in PDAC tissues than in adjacent noncancerous tissues (P<0.001). By immunohistochemistry, the data revealed that high FAT10 expression was significantly correlated with clinical stage (P<0.001), histological differentiation (P=0.004), and lymph node metastasis (P=0.013). Consistent with these results, we found that high expression of FAT10 was significantly correlated with poor survival in PDAC patients (P<0.001). Furthermore, Cox regression analyses showed that FAT10 expression was an independent predictor of overall survival. In conclusion, this study confirmed the overexpression of FAT10 and its association with tumor progression in PDAC. It also provided the first evidence that FAT10 expression in PDAC was an independent prognostic factor of patients, which might be a potential diagnostic and therapeutic target of PDAC.

Measuring rate constants for reactions of the simplest Criegee intermediate (CH2OO) by monitoring the OH radical.

While generating the CH2OO molecule by reacting CH2I with O2, significant amounts of the OH radical were observed by laser-induced fluorescence. At least two different processes formed OH. A fast process was probably initiated by a reaction of vibrationally hot CH2I radicals. The second process appeared to be associated with the decay of the CH2OO molecule. The addition of molecules known to react with CH2OO increased the observed decay rates of the OH signal. Using the OH signals as a proxy for the CH2OO concentration, the rate constant for the reaction of hexafluoroacetone with CH2OO was determined to be (3.33 ± 0.27) × 10(-11) cm(3) molecule(-1) s(-1), in good agreement with the value measured by Taatjes et al.1 The rate constant for the reaction of SO2 with CH2OO, (3.53 ± 0.29) × 10(-11) cm(3) molecule(-1) s(-1), showed no pressure dependence over the range of 50-200 Torr and was in agreement with the value at 4 Torr reported by Welz et al.

Resonant exchange of chiral Majorana Fermions modulated by two parallel quantum dots.

Resonant exchange of the chiral Majorana fermions (MFs) that is coupled to two parallel Majorana zero modes (MZMs) or two parallel quantum dots (QDs) is investigated. We find that, in the two QDs coupling case, the resonant exchange for the chiral MFs is analogous to that in the MZM coupling case. We further propose a circuit based on topological superconductor, which is formed by the proximity coupling of a quantum anomalous Hall insulator and a s-wave superconductor, to observe the resonant exchange of chiral MFs pairs. The numerical calculations show that the resonant transmission of the chiral MFs can be adjusted by varying the coupling parameters at superconductor phase differenceΔφ=π. It is particularly noteworthy that, by only modulating the coupling strength between the two QDs, the resonant exchange may be switched on or off. By adding another MZM, the non-Abelian braiding like operation can be realized. Therefore, our design scheme may provide another way for non-Abelian braiding operation of MFs and the findings may have potential application value in the realization of topological quantum computers.

The functions and mechanisms of RNA modification in prostate: Current status and future perspectives.

The increasing incidence and mortality of prostate cancer worldwide significantly impact the life span of male patients, emphasizing the urgency of understanding its pathogenic mechanism and associated molecular changes that regulate tumor progression for effective prevention and treatment. RNA modification, an important post-transcriptional regulatory process, profoundly influences tumor cell growth and metabolism, shaping cell fate. Over 170 RNA modification methods are known, with prominent research focusing on N6-methyladenosine, N7-methylguanosine, N1-methyladenosine, 5-methylcytidine, pseudouridine, and N4-acetylcytidine modifications. These alterations intricately regulate coding and non-coding RNA post-transcriptionally, affecting the stability of RNA and protein expression levels. This article delves into the latest advancements and challenges associated with various RNA modifications in prostate cancer tumor cells, tumor microenvironment, and core signaling molecule androgen receptors. It aims to provide new research targets and avenues for molecular diagnosis, treatment strategies, and improvement of the prognosis in prostate cancer.

Oxidation of the two-phase Nb/Nb5Si3 composite: the role of energetics, thermodynamics, segregation, and interfaces.

Oxidation behavior of the two-phase Nb/Nb(5)Si(3) composite is of significant importance for the potential applications of the composite at high-temperature conditions. We investigate the atomic-scale oxidation mechanism of the Nb/Nb(5)Si(3) composite with first-principles density-functional theory and thermodynamics analysis. In particular, the effects of energetics, thermodynamics, segregation, and interfaces are identified. The clean composite surface is found to be composed of both Nb(110) and Si-terminated Nb(5)Si(3)(001). Energetics and thermodynamics calculations show that, during the oxidation process, the Nb(110) surface is oxidized first, followed by the segregation of niobium of the Nb(5)Si(3)(001) surface and subsequent oxidation of the Nb element of Nb(5)Si(3). High coverage of oxygen results in dissolved oxygen in bulk Nb through the diffusion of oxygen in the surface and at the interface. The theoretical investigation also provides an explanation, at the atomic-scale, for the experimental observation that the oxidation layer is essentially composed of niobium oxide and almost free of silicon. Furthermore, the methodology of this work can be applied to investigations of the oxidation behavior of other two-phase and multi-phase composites.