Combined analysis of the metabolome and transcriptome reveals the metabolic characteristics and candidate genes involved in alkaloid metabolism in Heuchera micrantha Douglas ex Lindl.

BACKGROUND: Alkaloids, important secondary metabolites produced by plants, play a crucial role in responding to environmental stress. Heuchera micrantha, a well-known plant used in landscaping, has the ability to purify air, and absorb toxic and radioactive substances, showing strong environmental adaptability. However, there is still limited understanding of the accumulation characteristics and metabolic mechanism of alkaloids in H. micrantha. RESULTS: In this study, four distinct varieties of H. micrantha were used to investigate the accumulation and metabolic traits of alkaloids in its leaves. We conducted a combined analysis of the plant's metabolome and transcriptome. Our analysis identified 44 alkaloids metabolites in the leaves of the four H. micrantha varieties, with 26 showing different levels of accumulation among the groups. The HT and JQ varieties exhibited higher accumulation of differential alkaloid metabolites compared to YH and HY. We annotated the differential alkaloid metabolites to 22 metabolic pathways, including several alkaloid metabolism. Transcriptome data revealed 5064 differentially expressed genes involved in these metabolic pathways. Multivariate analysis showed that four key metabolites (N-hydroxytryptamine, L-tyramine, tryptamine, and 2-phenylethylamine) and three candidate genes (Cluster-15488.116815, Cluster-15488.146268, and Cluster-15488.173297) that merit further investigation. CONCLUSIONS: This study provided preliminarily insight into the molecular mechanism of the biosynthesis of alkaloids in H. micrantha. However, further analysis is required to elucidate the specific regulatory mechanisms of the candidate gene involved in the synthesis of key alkaloid metabolites. In summary, our findings provide important information about how alkaloid metabolites build up and the metabolic pathways involved in H. micrantha varieties. This gives us a good starting point for future research on the regulation mechanism, and development, and utilization of alkaloids in H. micrantha.

Widely targeted volatilomics and transcriptome analyses reveal the differences in volatile organic components in differently shaped Amomum tsao-ko fruits.

BACKGROUND: Amomum tsao-ko is an important aromatic crop used in medicines and food. It can be categorized into three main types based on the fruit shape: long (L), oval (O), and round (R). However, limited information is available on the volatile substances present in differently shaped A. tsao-ko fruits. This study investigated the characteristics and biosynthesis of volatile organic compounds (VOCs) in fresh and dried A. tsao-ko fruits of different shapes using widely targeted volatilomics and transcriptome analyses. RESULTS: In total, 978 VOCs, primarily terpenoids, esters, and heterocyclic compounds, were detected. The number of differentially accumulated volatile organic compounds (DAVOCs) in dried fruits of various shapes was significantly higher than that in fresh fruits, with terpenoids, esters, and heterocyclic compounds accounting for approximately 50% of the total DAVOCs. Notably, α-phellandrene, identified as a shared differential accumulated terpenoid across various fruit shapes, was detected in both fresh and dried fruits. Through transcriptome analysis, 40 candidate genes implicated in the terpenoid biosynthesis pathway were screened. An integrated analysis of the metabolome and transcriptome revealed that the structural genes HMGR-2, TPS7, TPS5-10, TPS21-3, TPS21-5, TPS21-6, TPS21-7, and TPS21-9, along with 81 transcription factors (including 17 NACs, 16 MYBs, 16 AP2/ERFs, 13 WRKYs, 13 bHLHs, and 6 bZIPs), co-regulate the biosynthesis of volatile terpenoids. CONCLUSIONS: This study expands our understanding of the volatile metabolism profile of A. tsao-ko and provides a solid foundation for future investigations of the mechanisms governing fruit quality.

Pathogen Profile of Klebsiella variicola, the Causative Agent of Banana Sheath Rot.

Banana (Musa spp.) is an important fruit and food crop worldwide. In recent years, banana sheath rot has become a major problem in banana cultivation, causing plant death and substantial economic losses. Nevertheless, the pathogen profile of this disease has not been fully characterized. Klebsiella variicola is a versatile bacterium capable of colonizing different hosts, such as plants, humans, insects, and animals, and is recognized as an emerging pathogen in various hosts. In this study, we obtained 12 bacterial isolates from 12 different banana samples showing banana sheath rot in Guangdong and Guangxi Provinces, China. Phylogenetic analysis based on 16S rRNA sequences confirmed that all 12 isolates were K. variicola strains. We sequenced the genomes of these strains, performed comparative genomic analysis with other sequenced K. variicola strains, and found a lack of consistency in accessory gene content among these K. variicola strains. However, prediction based on the pan-genome of K. variicola revealed 22 unique virulence factors carried by the 12 pathogenic K. variicola isolates. Microbiome and microbial interaction network analysis of endophytes between the healthy tissues of diseased plants and healthy plants of two cultivars showed that Methanobacterium negatively interacts with Klebsiella in banana plants and that Herbaspirillum might indirectly inhibit Methanobacterium to promote Klebsiella growth. These results suggest that banana sheath rot is caused by the imbalance of plant endophytes and opportunistic pathogenic bacteria, providing an important basis for research and control of this disease.[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Complete genome sequence of the kiwifruit bacterial canker pathogen Pseudomonas savastanoi strain MHT1.

BACKGROUND: Pseudomonas savastanoi is an important plant pathogen that infects and causes symptoms in a variety of economically important crops, causing considerable loss of yield and quality. Because there has been no research reported to date on bacterial canker of kiwifruit (Actinidia chinensis) plants caused by P. savastanoi and, in particular, no in-depth studies of the complete genome sequence or pathogenic mechanism, long-lasting and environmentally friendly control measures against this pathogen in kiwifruit are lacking. This study therefore has both theoretical value and practical significance. RESULTS: We report the complete genome sequence of P. savastanoi strain MHT1, which was first reported as the pathogen causing bacterial canker in kiwifruit plants. The genome consists of a 6.00-Mb chromosome with 58.5% GC content and 5008 predicted genes. Comparative genome analysis of four sequenced genomes of representative P. savastanoi strains revealed that 230 genes are unique to the MHT1 strain and that these genes are enriched in antibiotic metabolic processes and metabolic pathways, which may be associated with the drug resistance and host range observed in this strain. MHT1 showed high syntenic relationships with different P. savastanoi strains. Furthermore, MHT1 has eight conserved effectors that are highly homologous to effectors from P. syringae, Pseudomonas amygdali, and Ralstonia solanacearum strains. The MHT1 genome contains six genomic islands and two prophage sequences. In addition, 380 genes were annotated as antibiotic resistance genes and another 734 as encoding carbohydrate-active enzymes. CONCLUSION: The whole-genome sequence of this kiwifruit bacterial canker pathogen extends our knowledge of the P. savastanoi genome, sets the stage for further studies of the interaction between kiwifruit and P. savastanoi, and provides an important theoretical foundation for the prevention and control of bacterial canker.

DNA aptamers specific for Legionella pneumophila: systematic evolution of ligands by exponential enrichment in whole bacterial cells.

Legionella pneumophila is the major causative agent of Legionnaires' disease and Pontiac fever, which pose major public health problems. Rapid detection of L. pneumophila is important for global control of these diseases. Aptamers, short oligonucleotides that bind to targets with high affinity and specificity, have great potential for use in pathogenic bacterium detection, diagnostics, and therapy. Here, we used a whole-cell SELEX (systematic evolution of ligands by exponential enrichment) method to isolate and characterize single-stranded DNA (ssDNA) aptamers against L. pneumophila. A total of 60 ssDNA sequences were identified after 17 rounds of selection. Other bacterial species (Escherichia coli, Bacillus subtilis, Pseudomonas syringae, Staphylococcus aureus, Legionella quateirensis, and Legionella adelaidensis) were used for counterselection to enhance the specificity of ssDNA aptamers against L. pneumophila. Four ssDNA aptamers showed strong affinity and high selectivity for L. pneumophila, with Kd values in the nanomolar range. Bioinformatic analysis of the most specific aptamers revealed predicted conserved secondary structures that might bind to L. pneumophila cell walls. In addition, the binding of these four fluorescently labeled aptamers to the surface of L. pneumophila was observed directly by fluorescence microscopy. These aptamers identified in this study could be used in the future to develop medical diagnostic tools and public environmental detection assays for L. pneumophila.

Diagnostic methods and drug therapies in patients with ischemic colitis.

PURPOSE: Ischemic colitis (IC) is the most prevalent ischemic injury of thegastrointestinal tract. Clinical features of IC such as acute abdominal pain, hematochezia,and diarrhea are similar to those of acute mesenteric ischemia, inflammatorybowel disease, or infectious bowel disease, and their relative ambiguity candelay diagnosis and treatment. To comprehensively detail the current state ofdiagnostic methods and available drug therapies for detecting and treating IC,this review aims to provide a concise and practical summary of thecorresponding literature. METHODS: PubMed and Cochrane Library were searched toretrieve all published studies reporting the diagnostic methods and drugtherapies in patients with ischemic colitis. The search strategy of drugtherapy includes human and animal data. RESULTS: Colonoscopy combined with histopathologicalbiopsy is the standard of diagnosis for the IC. Most patients respond well tothe conservative treatment, and surgical consultation is needed when conservativetreatment is ineffective. Studies of potential drug therapy have beendeveloped, including phosphodiesterase type 5 inhibitors, pentoxifylline,rebamipide, prostaglandin E1, and polydeoxyribonucleotide. CONCLUSION: Accurate diagnoses and effective treatmentshave helped reduce the mortality rate and improve prognoses for patientsafflicted with IC, and corresponding drug therapies have been constantlyupdated as new research has emerged.

Co-Circulation of 4 Dengue Virus Serotypes among Travelers Entering China from Myanmar, 2017.

We report 301 dengue virus infections among cross-border travelers entering Yunnan Province, China, from Myanmar during 2017. Phylogenetic analysis of 99 strains found all 4 serotypes co-circulating; genetic characteristics have also changed. This finding highlights the urgent need for monitoring dengue virus cross-border transmission as early warning of severe dengue fever.

Intracellular Growth and Morphological Characteristics of Legionella pneumophila during Invasion and Proliferation in Different Cells.

Various studies have been made to attempt to study the interaction between Legionella pneumophila and the host cells. In this research, we successfully constructed a L. pneumophila mutant strain that stably expressed high levels of green fluorescent protein and used this strain to evaluate the adherence, invasion and proliferation of L. pneumophila in association with several cell lines, including seven cell lines [human macrophage-like cell lines (U937, THP-1), murine macrophage-like cell lines (J774.1A, Raw264.7), human bronchial epithelial cell lines (16HBE, Beas-2B) and human cerrical cancer cell line (HeLa)] which have been used as the host models of L. pneumophila, and two breast carcinoma cell lines (MCF-7 and MDA-MB-231). Our results showed that the two newly tested cell lines are able to support the intracellular proliferation of L. pneumophila, and there were some morphological variations during the invasion and intracellular replication of L. pneumophila in different cell lines. These results can help us find out the common and special patterns of invasion and proliferation of L. pneumophila within different hosts. This is conducive to our knowledge on the relationship and interaction between bacteria and host.

Antibiotic susceptibility of Legionella strains isolated from public water sources in Macau and Guangzhou.

The purpose of this study was to investigate the susceptibility of waterborne strains of Legionella to eight antimicrobials commonly used in legionellosis therapy. The minimum inhibitory concentrations (MICs) of 66 environmental Legionella strains, isolated from fountains and cooling towers of public facilities (hotels, schools, and shopping malls) in Macau and Guangzhou, were tested using the microdilution method in buffered yeast extract broth. The MIC50/MIC90 values for erythromycin, cefotaxime (CTX), doxycycline (DOC), minocycline (MIN), azithromycin, ciprofloxacin, levofloxacin (LEV), and moxifloxacin were 0.125/0.5 mg/L, 4/8 mg/L, 8/16 mg/L, 4/8 mg/L, 0.125/0.5 mg/L, 0.031/0.031 mg/L, 0.031/0.031 mg/L, and 0.031/0.062 mg/L, respectively. Legionella isolates were inhibited by either low concentrations of macrolides and fluoroquinolones, or high concentrations of CTX and tetracycline drugs. LEV was the most effective drug against different Legionella species and serogroups of L. pneumophila isolates. The latter were inhibited in decreasing order by MIN > CTX >DOC, while non-L. pneumophila isolates were inhibited by CTX> MIN >DOC. In this study, we evaluated drug resistance of pathogenic bacteria from the environment. This may help predict the emergence of drug resistance, improve patient outcomes, and reduce hospitalization costs.

KIF3C: an emerging biomarker with prognostic and immune implications across pan-cancer types and its experiment validation in gastric cancer.

Kinesin Family Member 3C (KIF3C) assumes a crucial role in various biological processes of specific human cancers. Nevertheless, there exists a paucity of systematic assessments pertaining to the contribution of KIF3C in human malignancies. We conducted an extensive analysis of KIF3C, covering its expression profile, prognostic relevance, molecular function, tumor immunity, and drug sensitivity. Functional enrichment analysis was also carried out. In addition, we conducted in vitro experiments to substantiate the role of KIF3C in gastric cancer (GC). KIF3C expression demonstrated consistent elevation in various tumors compared to their corresponding normal tissues. We further unveiled that heightened KIF3C expression served as a prognostic indicator, and its elevated levels correlated with unfavorable clinical outcomes, encompassing reduced OS, DSS, and PFS in several cancer types. Notably, KIF3C expression exhibited positive associations with the pathological stages of several cancers. Moreover, KIF3C demonstrated varying relationships with the infiltration of various distinct immune cell types in gastric cancer. Functional analysis outcomes indicated that KIF3C played a role in the PI3K-AKT signaling pathway. Drug sensitivity unveiled a positive relationship between KIF3C in gastric cancer and the IC50 values of the majority of identified anti-cancer drugs. Additionally, KIF3C knockdown reduced the proliferation, migration, and invasion capabilities, increased apoptosis, and led to alterations in the cell cycle of gastric cancer cells. Our research has revealed the significant and functional role of KIF3C as a tumorigenic gene in diverse cancer types. These findings indicate that KIF3C may serve as a promising target for the treatment of gastric cancer.

Dyadic effects of perceived stress, relationship satisfaction and distress disclosure on emotional distress in colorectal cancer patients and their family caregivers: An actor-partner interdependence mediation model.

Objective: This study adopted a dyadic analysis method to examine the effect of perceived stress on emotional distress and determine whether relationship satisfaction and distress disclosure act as mediators in colorectal cancer (CRC) enterostomy patient-caregiver dyads. Methods: A total of 312 patient-caregiver dyads completed measures assessing perceived stress, relationship satisfaction, distress disclosure, and emotional distress. The data were analyzed using the actor-partner interdependence mediation model. Results: This study found that the perceived stress of patients and caregivers both had direct and indirect actor effects on emotional distress (through relationship satisfaction). Another important finding is that perceived stress had indirect actor-partner effects (through distress disclosure) on emotional distress. Conclusions: This study highlights that perceived stress, relationship satisfaction, and distress disclosure of patients and their caregivers are key factors that can be considered for improving emotional distress. It also partially confirmed the interdependence of patients with CRC and their caregivers.

Distribution and safety evaluation of deoxynivalenol and its derivatives throughout the wheat product processing chain.

The distribution of deoxynivalenol (DON) and its derivatives 3-acetyldeoxynivalenol (3-Ac-DON) and 15-acetyldeoxynivalenol (15-Ac-DON) throughout the wheat processing chain were systemically evaluated by one-to-one corresponding studies of the whole processing chain. DON and its derivatives were determined by liquid chromatography-mass spectrometry (LC-MS/MS) in wheat grains and corresponding wheat bran, wheat flour, and semi-finished and finished wheat flour-based products. This investigation showed that wheat grain processing to wheat flour significantly decreased the levels of DON by approximately 52.7%-68.2%. Wheat flour processing of wheat flour-based products decreased the DON concentration by approximately 7.0%-70.6%. Among the processing methods, biscuit making showed the largest reduction (70.6%). The co-occurrence frequency of DON with low levels of 3-Ac-DON and 15-Ac-DON was significantly greater in wheat grains and wheat bran than in wheat flour. For wheat flour-based products, only the distribution pattern of 3-Ac-DON was observable in processed wheat flour products prepared using grains heavily contaminated with DON. In China, to the best of our knowledge, the processing factors (PFs) of DON in wheat flour and wheat flour-based products were systematically evaluated for the first time. The average PF of DON was 0.35 for wheat flour and the average PFs were 0.37-0.84 for wheat flour-based products, with biscuits having the smallest PF (0.37), indicating DON significantly decreasing in biscuit making. Furthermore, dietary exposure assessment of DON indicated an acceptable overall health risk in Chinese consumers, with the highest exposure being observed in infants and young children. This study provides important references for classified management of DON limits in wheat and its various products in China.

Comprehensive analysis of the tumor-promoting effect and immune infiltration correlation MAZ from pan-cancer to hepatocellular carcinoma.

BACKGROUND: Myc-associated zinc-finger protein (MAZ) is a transcription factor, which has been confirmed to be abnormally expressed in many tumors and involved in regulating the proliferation, migration, apoptosis, and autophagy of tumor cells. Currently, there is a lack of comprehensive analysis of MAZ in pan-cancer, and the mechanism of MAZ in hepatocellular carcinoma (HCC) and its association with immunotherapy remains unclear. METHODS: The expression, prognostic mutation, sCNA, and tumor immunity characteristics of MAZ in 33 types of tumors were analyzed by The Cancer Genome Atlas (TCGA), GEPIA, and TIMER databases. The association of MAZ expression levels with drug sensitivity, immunotherapy, immune checkpoints, and HLA-associated genes was further analyzed. Transwell, CCK-8, wound healing, and flow cytometry verified that MAZ affected the malignant cell behavior of HCC. The signaling pathways and cellular functions affected by MAZ in HCC were revealed by GSEA enrichment analysis. RESULTS: The expression level of MAZ was up-regulated, and the high expression of MAZ indicated a high-risk prognostic factor in most tumors, including ACC, BLCA, KIRP, LIHC, PRAD, SKCM, and THCA (p < 0.05). MAZ expression was positively correlated with the sensitivity of most chemotherapy drugs (p < 0.05). HLA-DQB2, HLA-H, and most immune checkpoint genes were remarkably up-regulated in the high MAZ expression group (p < 0.05). GSEA analysis revealed that MAZ expression was highly correlated with the intracellular immune-related functions and cancer-related signaling pathway, including the B cell receptor signaling pathway, complement activation, humoral immune response, TGF-ß signaling pathway, and Wnt signaling pathway. The overexpression of MAZ in HCC cells could promote the abilities of cell proliferation and migration and inhibit tumor cell apoptosis. CONCLUSION: Our study revealed that MAZ might play a role in promoting the progression of HCC. It was closely related to the tumor microenvironment, immune cell infiltration, and immune escape in pan-cancer. Moreover, this study provides new insights into MAZ as a prognostic marker and potential therapeutic target in HCC.

Comprehensive analysis of basement membrane and immune checkpoint related lncRNA and its prognostic value in hepatocellular carcinoma via machine learning.

Background: Hepatocellular carcinoma (HCC), which is characterized by its high malignancy, generally exhibits poor response to immunotherapy. As part of the tumor microenvironment, basement membranes (BMs) are involved in tumor development and immune activities. Presently, there is no integrated analysis linking the basement membrane with immune checkpoints, especially from the perspective of lncRNA. Methods: Based on transcriptome data from The Cancer Genome Atlas, BMs-related and immune checkpoint-related lncRNAs were identified. By applying univariable Cox regression and Machine learning (LASSO and SVM-RFE algorithm), a 10-lncRNA prognosis signature was constructed. The prognostic significance of this signature was assessed by survival analysis. GSEA, ssGSEA, and drug sensitivity analysis were conducted to investigate potential functional pathways, immune status, and clinical implications of guiding individual treatments in HCC. Finally, the promoting migration effect of LINC01224 was validated via in vitro experiments. Results: The multiple Cox regression, receiver operating characteristic curves, and stratified survival analysis of clinical subgroups exhibited the robust prognostic ability of the lncRNA signature. Results of the GSEA and drug sensitivity analysis revealed significant differences in potential functional pathways and response to drugs between the two risk groups. In addition, the risk level of HCC patients was distinctly correlated with immune cell infiltration status. More importantly, LINC01224 was independently associated with the OS of HCC patients (P < 0.05), suppressing the expression of LINC01224 inhibited the migration of HCC cells. Conclusion: This study developed a reliable signature for the prognosis of HCC based on BM and immune checkpoint related lncRNA, revealing that LINC01224 might be a prognostic biomarker for HCC associated with the progression of HCC.

Complete genome sequence of the Pogostemon cablin bacterial wilt pathogen Ralstonia solanacearum strain SY1.

BACKGROUND: Ralstonia solanacearum causes bacterial wilt of Pogostemon cablin which is an important aromatic herb and also the main materials of COVID-19 therapeutic traditional drugs. However, we are lacking the information on the genomic sequences of R. solanacearum isolated from P. cablin. OBJECTIVE: The acquisition and analysis of this whole-genome sequence of the P. cablin bacterial wilt pathogen. METHODS: An R. solanacearum strain, named SY1, was isolated from infected P. cablin plants, and the complete genome sequence was sequenced and analyzed. RESULTS: The SY1 strain contains a 3.70-Mb chromosome and a 2.18-Mb megaplasmid, with GC contents of 67.57% and 67.41%, respectively. A total of 3308 predicted genes were located on the chromosome and 1657 genes were located in the megaplasmid. SY1 strain has 273 unique genes compared with five representative R. solanacearum strains, and these genes were enriched in the plant-pathogen interaction pathway. SY1 possessed a higher syntenic relationship with phylotype I strains, and the arsenal of type III effectors predicted in SY1 were also more closely related to those of phylotype I strains. SY1 contained 14 and 5 genomic islands in its chromosome and megaplasmid, respectively, and two prophage sequences in its chromosome. In addition, 215 and 130 genes were annotated as carbohydrate-active enzymes and antibiotic resistance genes, respectively. CONCLUSION: This is the first genome-scale assembly and annotation for R. solanacearum which isolated from infected P. cablin plants. The arsenal of virulence and antibiotic resistance may as the determinants in SY1 for infection of P. cablin plants.

The plant protection preparation GZM improves crop immunity, yield, and quality.

Lauryl alcohol, a natural compound found in plants and other organisms, is widely used to make surfactants, food, and pharmaceuticals. GZM, a plant protection preparation with lauryl alcohol as its major component is thought to establish a physical barrier on the plant surface, but its physiological functions are unknown. Here, we show that GZM improves the performance of peanut (Arachis hypogaea) plants in both the laboratory and the field. We demonstrate that the treatment with GZM or lauryl alcohol raises the contents of several specific lysophospholipids and induces the biosynthesis of phenylpropanoids, flavonoids, and wax in various plant species. In the field, GZM improves crop immunity, yield, and quality. In addition, GZM and lauryl alcohol can inhibit the growth of some pathogenic fungi. Our findings provide insights into the physiological and biological effects of GZM treatment on plants and show that GZM and lauryl alcohol are promising preparations in agricultural production.

Biocontrol of bacterial wilt disease in tomato using Bacillus subtilis strain R31.

Bacterial wilt disease caused by Ralstonia solanacearum is a widespread, severe plant disease. Tomato (Solanum lycopersicum), one of the most important vegetable crops worldwide, is particularly susceptible to this disease. Biological control offers numerous advantages, making it a highly favorable approach for managing bacterial wilt. In this study, the results demonstrate that treatment with the biological control strain Bacillus subtilis R31 significantly reduced the incidence of tomato bacterial wilt. In addition, R31 directly inhibits the growth of R. solanacearum, and lipopeptides play an important role in this effect. The results also show that R31 can stably colonize the rhizosphere soil and root tissues of tomato plants for a long time, reduce the R. solanacearum population in the rhizosphere soil, and alter the microbial community that interacts with R. solanacearum. This study provides an important theoretical basis for elucidating the mechanism of B. subtilis as a biological control agent against bacterial wilt and lays the foundation for the optimization and promotion of other agents such as R31.

Assessing the Impact of Air Pollution on Inbound Tourism along the Yangtze River across Space and Time.

The prevalent air pollution along the Yangtze River Economic Belt (YREB) possesses a significant threat to the natural environment, which further affects nearby tourism destination development. The paper seeks to assess the impact of air pollution on tourism in this region through a 2002-2012 panel data of 31 prefecture-level cities, along with geographic information system (GIS) and cluster analyses. The results reveal that air pollution is negatively associated with the number of inbound tourists along the YREB. In general, when air pollution intensifies by 1%, the number of inbound tourists decreases by 1.171%. This impact is more evident when air pollution is more severe, in the long term, and in areas that are larger, more central, and with more tourism resources. The paper contributes to the literature by addressing common limitations in previous studies and providing a more comprehensive evaluation of air pollution's impact on inbound tourism in the YREB. Practical implications regarding public policies and development directions based on air pollution periods, regions, and tourism resource allocations are provided.

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.

Macronutrient content and fatty acid composition and their positional distribution in human breast milk from Zhejiang Province, China in different lactation periods.

Lactational changes in macronutrient content, lipid profile, fatty acid composition, and positional distribution of human breast milk were investigated in this study. A total of 378 milk samples of six different lactation periods, including 0‒5, 6‒14, 15‒30, 31‒90, 91‒180, and 181‒360 days, were collected cross-sectionally from healthy lactating women in Zhejiang, China. As lactation progressed from 0‒5 to 15‒30 days, the lipid content and the percentages of C10:0, C12:0, C14:0, C18:2n-6, and C18:3n-3 increased significantly, while the protein concentration and the proportions of phospholipids, cholesterols, C16:0, C18:1n-9, C24:1n-9, C20:4n-6, C22:4n-6, C22:5n-3, and C22:6n-3 decreased notably. When lactation was further extended to 181‒360 days, the protein content continued to decrease, and the percentages of C12:0 and C14:0 continued to increase, whereas the levels of other tested nutrients remained stable. Although the triacylglycerol positional distributions of some fatty acids underwent significant lactational variations, C14:0, C16:0, C24:1n-9, C22:4n-6, C22:5n-3, and C22:6n-3 were located mainly at the sn-2 position, while C18:1n-9, C18:2n-6, and C18:3n-3 were primarily distributed at the sn-1,3 positions. Compared with human breast milk reported in Western countries, samples in our study demonstrated higher percentages of C18:2n-6, C18:3n-3, C20:4n-6, and C22:6n-3, but lower proportions of C12:0, C14:0, and C18:1n-9. The results from this study indicated a nutritional composition different from that of the Western countries and may provide useful data for the development of infant formulas closer to Chinese breast milk in terms of the fatty acid composition and its specified positional distribution on triglyceride structure.