Autoantibody repertoire profiling in tissue and blood identifies colorectal cancer-specific biomarkers.

Autoantibodies (AAbs) in the blood of colorectal cancer (CRC) patients have been evaluated for tumor detection. However, it remains uncertain whether these AAbs are specific to tumor-associated antigens. In this study, we explored the IgG and IgM autoantibody repertoires in both the in situ tissue microenvironment and peripheral blood as potential tumor-specific biomarkers. We applied high-density protein arrays to profile AAbs in the tumor-infiltrating lymphocyte supernatants and corresponding serum from four patients with CRC, as well as in the serum of three noncancer controls. Our findings revealed that there were more reactive IgM AAbs than IgG in both the cell supernatant and corresponding serum, with a difference of approximately 3-5 times. Immunoglobulin G was predominant in the serum, while IgM was more abundant in the cell supernatant. We identified a range of AAbs present in both the supernatant and the corresponding serum, numbering between 432 and 780, with an average of 53.3% shared. Only 4.7% (n = 23) and 0.2% (n = 2) of reactive antigens for IgG and IgM AAbs, respectively, were specific to CRC. Ultimately, we compiled a list of 19 IgG AAb targets as potential tumor-specific AAb candidates. Autoantibodies against one of the top candidates, p15INK4b-related sequence/regulation of nuclear pre-mRNA domain-containing protein 1A (RPRD1A), were significantly elevated in 53 CRC patients compared to 119 controls (p < 0.0001). The project revealed that tissue-derived IgG AAbs, rather than IgM, are the primary source of tumor-specific AAbs in peripheral blood. It also identified potential tumor-specific AAbs that could be applied for noninvasive screening of CRC.

Plasma ofCS-modified CD44 predicts the survival of patients with lung cancer.

Plasma levels of oncofetal chondroitin sulfate (ofCS)-modified CD44 have emerged as a promising biomarker for multi-cancer detection. Here, we explored its potential to predict the survival of patients with lung cancer. A prospective observational cohort was conducted involving 274 newly diagnosed patients with lung cancer at the Sun Yat-sen University Cancer Center from 2013 to 2015. The plasma levels of ofCS-modified CD44 were measured, and Cox regression analysis was performed to assess the association between plasma-modified CD44 levels and overall survival (OS) as well as other prognostic outcomes. Prognostic nomograms were constructed based on plasma ofCS-modified CD44 levels to predict survival outcomes for patients with lung cancer. Patients with high expression ofCS-modified CD44 exhibited significantly worse outcomes in terms of OS (HR = 1.61, 95%CI = 1.13-2.29, p = 0.009) and progression-free survival (PFS). These findings were consistent across various analyses. The concordance index of the prognostic nomogram for predicting OS in both the training set and validation set were 0.723 and 0.737, respectively. Additionally, time-dependent receiver operating characteristic (ROC) curves showed that the nomogram could serve as a useful tool for predicting OS in patients with lung cancer. Plasma ofCS-modified CD44 may serve as an independent prognosis marker for patients with lung cancer. Further validation of its predictive value could enhance prognostic assessment and guide personalized treatment strategies for patients with lung cancer.

Molecular phylogenetic and estimation of evolutionary divergence and biogeography of the family Schizoparmaceae and allied families (Diaporthales, Ascomycota).

The Diaporthales includes 32 families, many of which are important plant pathogens, endophytes and saprobes, e.g., members of the families Pseudoplagiostomataceae, Pyrisporaceae and Schizoparmaceae. Nucleotide sequences derived from five genetic loci including: ITS, LSU, TEF1-α, TUB2 and RPB2 were used for Bayesian evolutionary analysis to determine divergence times and evolutionary relationships within the Schizoparmaceae. Molecular clock analyses revealed that the ancestor of Schizoparmaceae split during the Upper Cretaceous period approximately 75.7 Mya (95 % highest posterior density of 60.3-91.3 Mya). Reconstructing ancestral state in phylogenies (RASP) with using the Bayesian Binary Markov chain Monte Carlo (BBM) Method to reconstruct the historical biogeography for the family Schizoparmaceae indicated its most likely origin in Africa. Based on taxonomic and phylogenetic analyses, the Pseudoplagiostomataceae and Pyrisporaceae relationships were clarified and a total of four species described herein. For Pseudoplagiostomataceae, three new species and one known species that include, Pseudoplagiostoma fafuense sp. nov., Ps. ilicis sp. nov., Ps. sanmingense sp. nov. and Ps. bambusae are described and a key of Pseudoplagiostomataceae is provided. With respect to Pyrisporaceae, we considered Pseudoplagiostoma castaneae to be a synonym of Pyrispora castaneae. In addition, a new species of Schizoparmaceae, Coniella fujianensis sp. nov. is described and illustrated.

A hsa_circ_001726 axis regulated by E2F6 contributes to metastasis of hepatocellular carcinoma.

BACKGROUND: CircRNAs participate in the development of hepatocellular carcinoma (HCC). This work aims to explore the key tumor promoting circRNA as a gene therapy target. METHODS: The differentially expressed gene circRNAs in HCC tumor tissues was identified by mining GSE121714 dataset. EdU staining, wound healing, transwell invasion assay, TUNEL staining and western blotting examined proliferation, migration, invasion, apoptosis and epithelial mesenchymal transition (EMT). Xenograft mouse model and orthotopic transplantation tumor mouse model were constructed to verify the role of hsa_circ_001726 in growth and metastasis of HCC. The relationship among CCT2, E2F6, hsa_circ_001726, miR-671-5p and PRMT9 was identified by RNA-fluorescence in situ hybridization, luciferase reporter assay and RNA Immunoprecipitation. RESULTS: Eleven differentially expressed circRNAs were found in HCC tumors. Among them, hsa_circ_001726 was highly expressed in HCC tumors and cells, which was transcribed from CCT2. As a transcription factor of CCT2, E2F6 knockdown inactivated CCT2 promoter and reduced hsa_circ_001726 expression. Moreover, hsa_circ_001726 elevated PRMT9 expression by sponging miR-671-5p, and then activated Notch signaling pathway. Additionally, hsa_circ_001726 deficiency repressed malignant phenotypes of HCC cells, including proliferation, migration, invasion, EMT and apoptosis. In vivo, hsa_circ_001726 deficiency reduced tumor growth and lung metastasis of HCC in xenograft mouse models and orthotopic transplantation tumor mouse models. CONCLUSION: Hsa_circ_001726 functioned as an oncogene in HCC, which was derived from CCT2 and regulated by E2F6. Hsa_circ_001726 elevated PRMT9 expression by sponging miR-671-5p, and then activated Notch signaling pathway, thereby accelerating malignant phenotypes of HCC. Therefore, targeting hsa_circ_001726 may be a new avenue for HCC treatment.

Feedback regulation of the isoprenoid pathway by SsdTPS overexpression has the potential to enhance plant tolerance to drought stress.

In order to maintain the dynamic physiological balance, plants are compelled to adjust their energy metabolism and signal transduction to cope with the abiotic stresses caused by complex and changeable environments. The diterpenoid natural compound and secondary metabolites, sclareol, derived from Salvia sclarea, has gained significant attention owing to its economic value as a spice material and diverse physiological activities. Here, we focused on the roles and regulatory mechanisms of the sclareol diterpene synthase gene SsdTPS in the resistance of S. sclarea to abiotic stresses. Our results suggested that abiotic stresses could induce the response and upregulation of SsdTPS expression and isoprenoid pathway in S. sclarea. Ectopic expression of SsdTPS conferred drought tolerance in transgenic Arabidopsis, compared with wild-type. Overexpression of SsdTPS enhanced the transcription of ABA signal transduction synthetic regulators and induced the positive feedback upregulating key regulatory genes in the MEP pathway, thereby promoting the increase of ABA content and improving drought tolerance in transgenic plants. In addition, SsdTPS-overexpressed transgenic Arabidopsis improved the responses of stomatal regulatory genes and ROS scavenging enzyme activities and gene expression to drought stress. This promoted the stomatal closure and ROS reduction, thus enhancing water retention capacity and reducing oxidative stress damage. These findings unveil the potentially positive role of SsdTPS in orchestrating multiple regulatory mechanisms and maintaining homeostasis for improved abiotic stress resistance in S. sclarea, providing a novel insight into strategies for promoting drought resistance and cultivating highly tolerant plants.

Germacrone alleviates breast cancer-associated osteolysis by inhibiting osteoclastogenesis via inhibition of MAPK/NF-κB signaling pathways.

Bone is one of the most frequent sites for metastasis in breast cancer patients. Bone metastasis significantly reduces the survival time and the life quality of breast cancer patients. Germacrone (GM) can serve humans as an anti-cancer and anti-inflammation agent, but its effect on breast cancer-induced osteolysis remains unclear. This study aims to investigate the functions and mechanisms of GM in alleviating breast cancer-induced osteolysis. The effects of GM on osteoclast differentiation, bone resorption, F-actin ring formation, and gene expression were examined in vitro. RNA-sequencing and Western Blot were conducted to explore the regulatory mechanisms of GM on osteoclastogenesis. The effects of GM on breast cancer-induced osteoclastogenesis, and breast cancer cell malignant behaviors were also evaluated. The in vivo efficacy of GM in the ovariectomy model and breast cancer bone metastasis model with micro-CT and histomorphometry. GM inhibited osteoclastogenesis, bone resorption and F-actin ring formation in vitro. Meanwhile, GM inhibited the expression of osteoclast-related genes. RNA-seq analysis and Western Blot confirmed that GM inhibited osteoclastogenesis via inhibition of MAPK/NF-κB signaling pathways. The in vivo mouse osteoporosis model further confirmed that GM inhibited osteolysis. In addition, GM suppressed the capability of proliferation, migration, and invasion and promoted the apoptosis of MDA-MB-231 cells. Furthermore, GM could inhibit MDA-MB-231 cell-induced osteoclastogenesis in vitro and alleviate breast cancer-associated osteolysis in vivo human MDA-MB-231 breast cancer bone metastasis-bearing mouse models. Our findings identify that GM can be a promising therapeutic agent for patients with breast cancer osteolytic bone metastasis.

Genomic prediction and genome-wide association studies for additive and dominance effects for body composition traits using 50 K and imputed high-density SNP genotypes in Yunong-black pigs.

Body composition traits are complex traits controlled by minor genes and, in hybrid populations, are impacted by additive and nonadditive effects. We aimed to identify candidate genes and increase the accuracy of genomic prediction of body composition traits in crossbred pigs by including dominance genetic effects. Genomic selection (GS) and genome-wide association studies were performed on seven body composition traits in 807 Yunong-black pigs using additive genomic models (AM) and additive-dominance genomic models (ADM) with an imputed high-density single nucleotide polymorphism (SNP) array and the Illumina Porcine SNP50 BeadChip. The results revealed that the additive heritabilities estimated for AM and ADM using the 50 K SNP data ranged from 0.20 to 0.34 and 0.11 to 0.30, respectively. However, the ranges of additive heritability for AM and ADM in the imputed data ranged from 0.20 to 0.36 and 0.12 to 0.30, respectively. The dominance variance accounted for 23% and 27% of the total variance for the 50 K and imputed data, respectively. The accuracy of genomic prediction improved by 5% on average for 50 K and imputed data when dominance effect were considered. Without the dominance effect, the accuracies for 50 K and imputed data were 0.35 and 0.38, respectively, and 0.41 and 0.43, respectively, upon considering it. A total of 12 significant SNP and 16 genomic regions were identified in the AM, and 14 significant SNP and 21 genomic regions were identified in the ADM for both the 50 K and imputed data. There were five overlapping SNP in the 50 K and imputed data. In the AM, a significant SNP (CNC10041568) was found in both body length and backfat thickness traits, which was in the PLAG1 gene strongly and significantly associated with body length and backfat thickness in pigs. Moreover, a significant SNP (CNC10031356) with a heterozygous dominant genotype was present in the ADM. Furthermore, several functionally related genes were associated with body composition traits, including MOS, RPS20, LYN, TGS1, TMEM68, XKR4, SEMA4D and ARNT2. These findings provide insights into molecular markers and GS breeding for the Yunong-black pigs.

Comparison of Double-Stranded DNA at the 5' and 3' Ends of the G-Triplex and Its Application in the Detection of Hg(II).

Leveraging the fluorescence enhancement effect of the G-triplex (G3)/thioflavin T (ThT) catalyzed by the adjacent double-stranded DNA positioned at the 5' terminus of the G3, the G3-specific oligonucleotide (G3MB6) was utilized to facilitate the rapid detection of mercury (Hg(II)) through thymine-Hg(II)-thymine (T-Hg(II)-T) interactions. G3MB6 adopted a hairpin structure in which partially complementary strands could be disrupted with the presence of Hg(II). It prompted the formation of double-stranded DNA by T-Hg(II)-T, inducing the unbound single strand of G3MB6 to spontaneously form a parallel G3 structure, producing a solid fluorescence signal by ThT. Conversely, fluorescence was absent without Hg(II), since no double strand and formation of G3 occurred. The fluorescence intensity of G3MB6 exhibited a positive correlation with Hg(II) concentrations from 17.72 to 300 nM (R2 = 0.9954), boasting a notably low quality of limitation (LOQ) of 17.72 nM. Additionally, it demonstrated remarkable selectivity for detecting Hg(II). Upon application to detect Hg(II) in milk samples, the recovery rates went from 100.3% to 103.2%.

Genomic Landscapes of Epstein-Barr Virus in Pulmonary Lymphoepithelioma-Like Carcinoma.

Epstein-Barr virus (EBV) infection is associated with multiple malignancies, including pulmonary lymphoepithelioma-like carcinoma (pLELC), a particular subtype of primary lung cancer. However, the genomic characteristics of EBV related to pLELC remain unclear. Here, we obtained the whole-genome data set of EBV isolated from 78 pLELC patients and 37 healthy controls using EBV-captured sequencing. Compared with the reference genome (NC_007605), a total of 3,995 variations were detected across pLELC-derived EBV sequences, with the mutational hot spots located in latent genes. Combined with 180 published EBV sequences derived from healthy people in Southern China, we performed a genome-wide association study and identified 32 variations significantly related to pLELC (P < 2.56 × 10-05, Bonferroni correction), with the top signal of single nucleotide polymorphism (SNP) coordinate T7327C (OR = 1.22, P = 2.39 × 10-15) locating in the origin of plasmid replication (OriP). The results of population structure analysis of EBV isolates in East Asian showed the EBV strains derived from pLELC were more similar to those from nasopharyngeal carcinoma (NPC) than other EBV-associated diseases. In addition, typical latency type-II infection were recognized for EBV of pLELC at both transcription and methylation levels. Taken together, we defined the global view of EBV genomic profiles in pLELC patients for the first time, providing new insights to deepening our understanding of this rare EBV-associated primary lung carcinoma. IMPORTANCE Pulmonary lymphoepithelioma-like carcinoma (pLELC) is a rare, distinctive subtype of primary lung cancer closely associated with Epstein-Barr virus (EBV) infection. Here, we gave the first overview of pLELC-derived EBV at the level of genome, methylation and transcription. We obtained the EBV sequences data set from 78 primary pLELC patients, and revealed the sequences diversity across EBV genome and detected variability in known immune epitopes. Genome-wide association analysis combining 217 healthy controls identifies significant variations related to the risk of pLELC. Meanwhile, we characterized the integration landscapes of EBV at the genome-wide level. These results provided new insight for understanding EBV's role in pLELC tumorigenesis.

Association of milk consumption with all-cause mortality and cardiovascular outcomes: a UK Biobank based large population cohort study.

BACKGROUND: The association of milk consumption with mortality and cardiovascular disease (CVD) outcomes was unclear. OBJECTIVE: The present study was performed to reveal the association of full cream, semi-skimmed, skimmed, soy, and other milk with all-cause mortality and CVD outcomes. METHODS: A prospective cohort study was performed using data from the UK Biobank. This study recruited 450,507 participants without CVD at baseline between 2006 and 2010 from UK Biobank and followed them up through 2021. Cox proportional hazard models were adopted to calculate the hazard ratios (HRs) and 95% confidence interval (CI) to understand the correlation between milk consumption and clinical outcomes. Subgroup and sensitivity analyses were further conducted. RESULTS: Among the participants, 435,486 (96.7%) were milk consumers. Multivariable model indicated that the adjusted HR of association between milk consumption and all-cause mortality was 0.84 (95% CI 0.79 to 0.91; P = 0.000) for semi-skimmed milk; 0.82 (0.76 to 0.88; P = 0.000) for skimmed milk and 0.83 (0.75 to 0.93; P = 0.001) for soy milk. Semi-skimmed, skimmed, and soy milk use were significantly related to lower risks of CVD mortality, CVD event, and stroke. CONCLUSION: Compared with non-milk users, semi-skimmed milk, skimmed milk, and soy milk consumption were related to a lower risk of all-cause mortality and CVD outcomes. Among them, skim milk consumption was more beneficial for all-cause mortality, while soy milk consumption was more beneficial for CVD outcomes.

Association of oily fish and nonoily fish intakes with all-cause mortality and cause-specific mortality: a large population-based prospective study.

BACKGROUND: There are inconsistent results of cohort studies analyzing the association between fish intake and mortality. OBJECTIVE: This study was performed to explore the association of oily fish consumption and nonoily fish consumption with all-cause mortality and cause-specific mortality. METHODS: A total of 431,062 participants from the UK Biobank who were without cancer or cardiovascular disease (CVD) at baseline between 2006 and 2010 were included in this study, and they were followed up through 2021. We constructed Cox proportional hazard models to calculate the hazard ratio (HR) and 95% confidence interval (CI) to assess the correlation of oily fish and nonoily fish intakes with mortality. Then, we performed subgroup analyses, and sensitivity analyses were developed and performed to examine the robustness of this study. RESULTS: Among the participants, 383,248 (88.9%) and 410,499 (95.2%) consumed oily fish and nonoily fish, respectively. Compared with the participants who did not consume oily fish, the adjusted HRs for the association of oily fish consumption (1 serving/week) with all-cause mortality and CVD mortality were 0.93 (0.87 to 0.98; p < 0.05) and 0.85 (0.74 to 0.98; p < 0.05), respectively. The multivariable-adjusted HRs of all-cause mortality for those who reported consuming < 1 serving/week of oily fish were 0.92 (0.86 to 0.98; p < 0.05). CONCLUSION: Compared with participants who reported never consuming oily fish, the consumption of oily fish with 1 serving/week was more beneficial for all-cause and CVD mortality.

Arginine methylation of HSPA8 by PRMT9 inhibits ferroptosis to accelerate hepatitis B virus-associated hepatocellular carcinoma progression.

BACKGROUND: The hepatitis B virus X (HBx) protein is an established cause of hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC). Whether arginine methylation regulates ferroptosis involved in HBx-induced HCC progression has not been reported. This study aimed to explore whether HBx-regulated protein arginine methyltransferase 9 (PRMT9) mediates the involvement of ferroptosis in the development of HCC. METHODS AND RESULTS: HBx inhibited ferroptosis through promoting PRMT9 expression in HCC cells. PRMT9 suppressed ferroptosis to accelerate HCC progression in vivo. PRMT9 targeted HSPA8 and enhanced arginine methylation of HSPA8 at R76 and R100 to regulate ferroptosis in HCC. HSPA8 overexpression altered the transcriptome profile of HepG2 cells, in particular, ferroptosis and immune-related pathways were significantly enriched by differentially expressed genes, including CD44. HSPA8 overexpression up-regulated CD44 expression and knockdown of CD44 significantly reversed the inhibition of ferroptosis caused by PRMT9 overexpression. CONCLUSIONS: In conclusion, HBx/PRMT9/HSPA8/CD44 axis is a vital signal pathway regulating ferroptosis in HCC cells. This study provides new opportunities and targets for the treatment of HBV-induced HCC.

Prognostic value of Hematoxylin and eosin staining tumor-infiltrating lymphocytes (H&E-TILs) in patients with esophageal squamous cell carcinoma treated with chemoradiotherapy.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) by routine hematoxylin and eosin staining (H&E-TILs) are a robust prognostic biomarker in various cancers. However, the role of H&E-TILs in esophageal squamous cell carcinoma (ESCC) treated with concurrent chemoradiotherapy (CCRT) has not been reported. The purpose of this study was to assess the prognostic value of H&E-TILs in ESCC treated with CCRT. METHODS: The clinical data of 160 patients with ESCC treated with CCRT in our center between Jan. 2014 and Dec. 2021 were collected and retrospectively reviewed, and propensity score matching (PSM) analyses were performed. The H&E-TILs sections before CCRT were reassessed by two experienced pathologists independently. The H&E-TILs sections were classified into a positive group (+, > 10%) and a negative group (-, ≤ 10%) using 10% as the cutoff. The effects of H&E-TILs on overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) were explored using the Kaplan‒Meier method, and the log-rank test was used to test the differences. Multivariable analysis was performed using the Cox proportion hazards model. RESULTS: The short-term response to CCRT and the OS (P < 0.001), DMFS (P = 0.001), and LRFS (P < 0.001) rates were significantly different between the H&E-TILs (+) and H&E-TILs (-) groups. Subgroup analysis showed that H&E-TILs(+) with CR + PR group had a longer survival than H&E-TILs(-) with CR + PR, H&E-TILs(+) with SD + PD and H&E-TILs(-) with SD + PD group, respectively(P < 0.001). Furthermore, based on TCGA data, patients in the high TILs group had a better prognosis than those in the low TILs group. Multivariate analyses indicated that H&E-TILs and the short-term response to CCRT were the only two independent factors affecting OS, PFS, DMFS, and LRFS simultaneously, and H&E-TILs expression was associated with an even better prognosis for those patients with CR + PR. CONCLUSIONS: H&E-TILs may be an effective and beneficial prognostic biomarker for ESCC patients treated with CCRT. Patients with H&E-TILs (+) with PR + CR would achieve excellent survival. Further prospective studies are required to validate the conclusions.

General anaesthesia, the developing brain, and cerebral white matter alterations: a narrative review.

The potential neurotoxic impact of anaesthetic agents has been the subject of sustained debate and continuing research. White matter, which comprises more than half of the brain volume and largely consists of myelinated axonal bundles, is critical for communication between diverse brain regions and for supporting neurobehavioural function. Evidence points to a correlation between exposure to anaesthesia and white matter alterations, which might underpin the ensuing cognitive and behavioural abnormalities. This review summarises the neuropathological and neuroimaging findings related to anaesthesia-induced white matter alterations in the developing brain. Future research is required to understand the effects of anaesthesia exposure on white matter development.

Retention effect and mode of capillary zone on the migration process of LNAPL pollutants based on experimental exploration.

Two-dimensional sand tank experiments were designed to investigate the retention process of the capillary zone during the migration of light non-aqueous phase liquid (LNAPL) pollutants. The fine sand and silt media experiments simulated the LNAPL migration process given a shallow point source leakage scenario. The results indicate that the LNAPL was retained in the capillary zone. A retention factor, based on the ratio of the change in the vertical migration velocity of the LNAPL front with time, was proposed to quantitatively characterize the retention effect. The retention factor and time satisfied the function of σ=A×exp(-kt). And the retention factor increased gradually with time, indicating the enhanced retention effect of capillary zone on the vertical migration of LNAPL. The concentration change rate was then used to investigate the LANPL redistribution process, which had a relationship with time of νc=B×ln(t)+C. The capillary zone could be divided from top to bottom into a weak retention zone (B > 0, vc < 0), a strong retention zone (B < 0), and a barrier zone (B > 0, vc > 0). The retention effect of capillary zone on LNAPL migration gradually strengthened during the vertical migration of LNAPL. In addition, the coefficient B had a relationship with the environmental factors (i.e., EC, pH, and ORP) of B=a×sin(b×α×ß×γ)c and the fitting coefficient R2 of the function was above 0.913 for both media, indicating a strong correlation between the LNAPL redistribution process and the key environmental factors.

Programmed intermittent epidural bolus in maintenance of epidural labor analgesia: a literature review.

Programmed intermittent epidural bolus (PIEB), administered by the infusion pump programmed to deliver boluses of epidural solution at certain intervals, is gradually gaining more attention as a technique to maintain the labor analgesia in recent years. Many studies find that it may have some advantages when compared with other methods. However, its exact effectiveness and optimal regimen are still unclear. We conducted a literature search in PubMed, Web of Science, and Cochrane Database of Systematic Reviews for studies published between January 2010 and June 2022. Of the 263 publications identified, 27 studies were included. The purpose of this review is to discuss the effects of PIEB with continuous epidural infusion (CEI) and patient-controlled epidural analgesia (PCEA) in maintenance of epidural labor analgesia on labor outcomes and elucidate the latest research progress of implementation strategies.

Genomic landscape of Epstein-Barr virus in familial nasopharyngeal carcinoma.

To better understand the genomic characteristics of Epstein-Barr virus (EBV) in familial nasopharyngeal carcinoma (NPC), we sequenced the EBV genomes by whole-genome capture in 38 unrelated patients with NPC family history in first-degree relatives and 47 healthy controls, including 13 with family history and 34 without. Compared with type 1 reference genome, mutation hotspots were observed in the latent gene regions of EBV in familial NPC cases. Population structure analysis showed that one cluster has a higher frequency in familial cases than in controls (OR=5.33, 95 % CI 2.50-11.33, P=1.42×10-5), and similar population structure composition was observed among familial and sporadic NPC cases in high-endemic areas. By genome-wide association analysis, four variants were found to be significantly associated with familial NPC. Consistent results were observed in the meta-analysis integrating two published case-control EBV sequencing studies in NPC high-endemic areas. High-risk haplotypes of EBV composed of 34 variants were associated with familial NPC risk (OR=13.85, 95 % CI 4.13-46.44, P=2.06×10-5), and higher frequency was observed in healthy blood-relative controls with NPC family history (9/13, 69.23 %) than those without family history (16/34, 47.06%). This study suggested the potential contribution of EBV high-risk subtypes to familial aggregation of NPC.

Ferroptosis is involved in regulating perioperative neurocognitive disorders: emerging perspectives.

Since the twenty-first century, the development of technological advances in anesthesia and surgery has brought benefits to human health. However, the adverse neurological effects of perioperative-related factors (e.g., surgical trauma, anesthesia, etc.) as stressors cannot be ignored as well. The nervous system appears to be more "fragile" and vulnerable to damage in developing and aging individuals. Ferroptosis is a novel form of programmed cell death proposed in 2012. In recent years, the regulation of ferroptosis to treat cancer, immune system disorders, and neurodegenerative diseases have seen an unprecedented surge of interest. The association of ferroptosis with perioperative neurocognitive disorders has also received much attention. Cognitive impairment can not only affect the individual's quality of life, but also impose a burden on the family and society. Therefore, the search for effective preventive and therapeutic methods to alleviate cognitive impairment caused by perioperative-related factors is a challenge that needs to be urgently addressed. In our review, we first briefly describe the connection between iron accumulation in neurons and impairment of brain function during development and aging. It is followed by a review of the pathways of ferroptosis, mainly including iron metabolism, amino acid metabolism, and lipid metabolism pathway. Furthermore, we analyze the connection between ferroptosis and perioperative-related factors. The surgery itself, general anesthetic drugs, and many other relevant factors in the perioperative period may affect neuronal iron homeostasis. Finally, we summarize the experimental evidence for ameliorating developmental and degenerative neurotoxicity by modulating ferroptosis. The suppression of ferroptosis seems to provide the possibility to prevent and improve perioperative neurocognitive impairment.

Asymmetric Condensation Characteristics during Dropwise Condensation in the Presence of Non-condensable Gas: A Lattice Boltzmann Study.

In this work, the condensation characteristics of droplets considering the non-condensable gas with different interaction effects are numerically studied utilizing a multicomponent multiphase thermal lattice Boltzmann (LB) model, with a special focus on the asymmetric nature induced by the interaction effect. The results demonstrate that for isolated-like growth with negligible interactions, the condensation characteristics, that is, the concentration profile, the temperature distribution, and the flow pattern, are typically symmetric in nature. For the growth regime in a pattern, the droplet has to compete with its neighbors for catching vapor, which leads to an overlapping concentration profile (namely the interaction effect). The distribution of the condensation flux on the droplet surface is consequently modified, which contributes to the asymmetric flow pattern and temperature profile. The condensation characteristics for droplet growth in a pattern present an asymmetric nature. Significantly, the asymmetric condensation flux resulting from the interaction effect can induce droplet motion. The results further demonstrate that the interaction strongly depends on the droplet's spatial and size distribution, including two crucial parameters, namely the inter-distance and relative size of droplets. The asymmetric condensation characteristics are consequently dependent on the difference in the interaction intensities on both sides of the droplet. Finally, we demonstrate numerically and theoretically that the evolution of the droplet radius versus time can be suitably described by a power law; the corresponding exponent is kept at a constant of 0.50 for isolated-like growth and is strongly sensitive to the interaction effect for the growth in a pattern.

Overlapping promoter library designed for rational heterogenous expression in Cordyceps militaris.

BACKGROUND: Cordyceps militaris, a kind of edible and medicinal fungus widely accepted in East Asia, has attracted much attention as a potential cell factory for producing adenosine analogs. Despite the rapid development in gene editing techniques and genome modeling, the diversity of DNA elements in C. militaris was too short to achieve rational heterogeneous expression for metabolic engineering studies. RESULTS: In this study, PtrpC, a kind of promoter with a relatively appropriate expression level and small size, was selected as a monomer for promoter library construction. Through in vitro BioBricks assembly, 9 overlapping PtrpC promoters with different copy numbers as well as reporter gene gfp were connected and subsequently integrated into the genome of C. militaris. Both the mRNA transcription level and the expression level of gene gfp gradually increased along with the copy number of the overlapping promoter NPtrpC and peaked at 7. In the meantime, no significant difference was found in either the biomass or morphological characteristic of engineered and wild-type strains. CONCLUSIONS: This study firstly expanded the overlapping promoter strategy used in model microorganism in C. militaris. It was a proof-of-concept in fungi synthetic biology and provide a general method to pushed the boundary of promoter engineering in edible mushroom.