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Beta-lactoglobulin is considered to be the major allergenic protein in milk. Lactic acid bacteria (LAB) possess a protein hydrolysis system that holds great promise for hydrolyzing β-LG and reducing its allergenicity. Therefore, this study aimed to screen LAB with β-LG hydrolysis activity from Yunnan traditional fermented foods. The results showed that Pediococcus pentosaceus C1001, Pediococcus acidilactici E1601–1, and Lactobacillus paracasei E1601–2 could effectively hydrolyze β-LG and further reduce its sensitization (more than 40%). All 3 LAB hydrolyzed β-LG allergenic fragments V41–K60 and L149–I162. Moreover, they encode a variety of genes related to proteolysis, such as aminopeptidase pepC and pepN , proline peptidase pepIP and endopeptidase pepO ; L. paracasei also E1601–2 contains extracellular protease coding gene prtP. They also encode a variety of genes associated with hydrolyzed proteins. The 3 strains screened in this study can be used to develop hypoallergenic dairy products. The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. [ABSTRACT FROM AUTHOR]

Melon is an important cash crop grown worldwide, with China leading the world in melon acreage. Melon wilt is becoming more common as the area under melon cultivation gradually increases. Therefore, it is crucial to understand the resistance pattern of Fusarium wilt in melons. In this work, among the four test melon cultivars, YG was highly resistant to Fusarium wilt and 1455 was disease‐resistant. However, 5657 was susceptible, while 5455 was highly susceptible to the disease. We detected 71,852 differentially expressed genes in 16 combinations, including 37,382 with up‐regulation and 3470 with down‐regulation, and we investigated 11 genes associated with resistance to Fusarium wilt through bioinformatics and transcriptome analysis. We identified two differentially expressed cinnamyl alcohol dehydrogenases (CAD) that were down‐regulated in the susceptible melon material in contrast to the resistant variety. Nine chitinase (CHT) genes were differentially expressed, with four showing up‐regulation and four showing down‐regulation in the susceptible compared to the resistant melon material. The MeloCHT genes were located on chromosomes 2, 6, 8, 11 and 12, with four of them on chromosome 8. MeloCAD1 was located on chromosome 1 and MeloCAD2 on chromosome 8. The physicochemical properties of the encoded proteins were predicted by bioinformatics, including theoretical isoelectric point, instability coefficient, relative molecular mass, lipid solubility index and hydrophilicity index. The genes encode proteins with α‐helix, extended strand, random coils and β‐turns. This study provides fundamental knowledge on the transcriptome of melons and establishes a foundation for future research on the detection and application of Fusarium wilt‐resistant genes in melons. [ABSTRACT FROM AUTHOR]

Background: Spontaneous remission of cancer is a rare and poorly understood phenomenon characterized by complete or partial remission of a malignancy in the absence of or with inadequate treatment. The underlying mechanism for such occurrences is poorly understood, however, immune mechanisms seem to play an important role in such cases. In recent years increasingly more data have become available in favor of the clinical benefit of low levels of chimerism in hematologic malignancies. One such instance of naturally occurring low-level chimerism is feto-maternal microchimerism which has been shown to influence cancer progression and, in some instances, to be a protective factor against malignancy. Case report: We report a case of a young female patient with aggressive primary mediastinal large B cell lymphoma refractory to two lines of chemo-immunotherapy achieving sustained complete metabolic remission of tumor while pregnant with twins. Results: A focus on feto-maternal microchimerism during and after pregnancy revealed transient levels of feto-maternal microchimerism in the peripheral blood of the patient as measured by quantifying the Y-chromosome-linked SRY gene. Conclusions: Microchimerism presents significant potential for enhancing our comprehension of disease mechanisms, uncovering novel therapeutic targets, and refining diagnostic and treatment approaches, especially concerning cancer. [ABSTRACT FROM AUTHOR]

Background: Oral tissue morphogenesis is innately determined and genetically controlled by underlying connective tissue. The connective tissue graft (CTG) harvested from palatal donor sites originally retains "regional specificity" and is considered to be responsible for epithelial keratinization. Methods: This case study presents histological and genomic outcomes of coronally advanced flap (CAF) with CTG for the management of marginal tissue recession (MTR). The tissue samples harvested at 12‐month postoperative period, during the debulking procedure of the treated site were subjected to Masson's trichrome staining (MTS) and whole‐genome sequencing (WGS). Results: Clinically, the mean root coverage as compared to baseline at 6 months (90%), 12 months (95%), and 24 months (95%) postoperatively was achieved. Overbulking of treated site was evident even after 12 months. Nevertheless, clinically discernible alterations in epithelial keratinization were not present. Although MTS revealed areas of non‐keratinization and para‐keratinization, WGS revealed a significant expression of keratinization genes, neural crest, and positional marker genes. Conclusions: CAF with CTG is still considered the "gold standard" in treatment of MTR. The keratinization of overlying epithelium at sites hitherto where non‐keratinized mucosa is advanced over CTG may not be complete even after 12 months. It is evident from the analysis of the reported case that clinically such sites may appear non‐keratinized despite the expression of genes for keratinization. The complex interplay between genomic and phenotypic expressions serves as a foundation of biological concepts. Nevertheless, it is imperative to acknowledge that the phenotype of an organism is not solely determined by genetic expression and is often influenced by a complex interaction between genetic background and environmental factors. Key Summary: The connective tissue serves as a medium for transmitting the genetic code and exerting an influence on the properties of the overlying epithelial tissue. Concrete evidence implies connective tissue plays a significant role in influencing the keratinization process of the overlying epithelium.Epithelial keratinization following a coronally advanced flap with connective tissue graft is also governed by environmental factors in addition to inherent potential within the graft.Differences in gene expression profiles may vary from individuals, teeth and among sites. [ABSTRACT FROM AUTHOR]

Pear black spot, caused by A. gaisen during fruit growth, is a disease that significantly reduces pear yield. Biological control using antagonistic microorganisms is regarded as a viable alternative to chemical agents. The discovery of TRM76147, a novel species of Streptomyces isolated from the Taklamakan Desert, has demonstrated promising potential in addressing this issue. This study was conducted to determine the potential of crude extract of Streptomyces sp. nov., strain TRM76147, for control of A. gaisen. TRM76147 is closely related to Streptomyces griseoviridis NBRC 12874T, exhibiting an average nucleotide identity (ANI) value of 82.13%. Combined with the polyphasic taxonomic identification, this suggests that TRM76147 is a potentially new species. Through analyses using BigSCAPE and antiSMASH, it was determined that the TRM76147 genome contains 19 gene clusters. The ethyl acetate extract of this strain demonstrates antifungal activity, with the active substance remaining stable at temperatures up to 70 °C, achieving an activity level of 16.23 ± 0.22 mm. Furthermore, the crude extract maintains its antifungal efficacy across a pH range of 2 to 12. Notably, the antifungal diameter was recorded at 16.53 ± 0.12 mm following 80 min of UV irradiation. Under different treatment conditions, TRM76147 fermentation crude extract caused A. gaisen spore crumpling and spore number reduction. In addition, this study also found that the TRM76147 fermentation broth could control the production of pear black spot disease, which initially revealed the inhibition mechanism. The abundant actinomycete resources in this study have good application and development value in the discovery of new species and the study of bioactive substances and biological control. [ABSTRACT FROM AUTHOR]

This work provides insights into the effect of fire on soil processes in Mediterranean-type ecosystems in Cyprus. Soil samples from mountainous sites that were subjected to a summer wildfire and adjacent control samples were collected. Incubations were used to estimate basal respiration and isolate soil CO2 release of heterotrophic microorganisms from autotrophic root respiration and heterotrophic respiration from litter decomposition. Physicochemical property changes, bacteria community changes using DNA extraction and 16S rRNA gene analysis, and the effects of ash and fresh litter addition were studied to reveal the microbial composition and the post-fire soil function. Laboratory incubation showed that burned soils constantly showed higher microbial respiration rates compared with control unburned areas, even six months after a fire. Adding ash to unburned samples increased microbial respiration, suggesting that increased nutrient availability positively corelates with the increased release of CO2 from fire-affected soil. Elevated temperatures due to the wildfire exerted significant effects on the composition of soil bacterial microbiota. Nevertheless, the wildfire did not affect the alpha-diversity of soil bacteria. New communities of microorganisms are still able to decompose fresh plant material after a fire, but at a slower rate than natural pre-fire populations. [ABSTRACT FROM AUTHOR]

Background: Cellular senescence is pivotal in the occurrence and progression of atrial fibrillation (AF). This study aimed to identify senescence-related genes that could be potential therapeutic biomarkers for AF. Methods: AF-related differentially expressed genes (DEGs) were identified using the Gene Expression Omnibus dataset. Weighted gene co-expression network analysis (WGCNA) was used to analyze important modules and potential hub genes. Integrating senescence-related genes, potential biomarkers were identified. Their differential expression levels were then validated in human atrial tissue, HL-1 cells, and Angiotensin II-infused mice. Finally, molecular docking analysis was conducted to predict potential interactions between potential biomarkers and the senolytic drug Navitoclax. Results: We identified seven genes common to AF-related DEGs and senescence-related genes. Three significant modules were selected from WGCNA analysis. Taken together, three senescence-related genes (ETS1, SP1, and WT1) were found to be significantly associated with AF. Protein-protein interaction network analysis revealed biological connections among the predicted target genes of ETS1, SP1, and WT1. Notably, ETS1, SP1, and WT1 exhibited significant differential expression in clinical samples as well as in vitro and in vivo models. Molecular docking revealed favorable binding affinity between senolytic Navitoclax and these potential biomarkers. Conclusions: This study highlights ETS1, SP1, and WT1 as crucial senescence-related genes associated with AF, offering potential therapeutic targets, with supportive evidence of binding affinity with senolytic Navitoclax. These findings provide novel insights into AF pathogenesis from a senescence perspective.

Abstract Background Cancer is a fatal disease that severely affects humans. Designing new anticancer strategies and understanding the mechanism of action of anticancer agents is imperative. Hypothesis/Purpose In this study, we evaluated the utility of metformin and D-limonene, alone or in combination, as potential anticancer therapeutics using the human liver and breast cancer cell lines HepG2 and MCF-7. Study design An integrated systems pharmacology approach is presented for illustrating the molecular interactions between metformin and D-limonene. Methods We applied a systems-based analysis to introduce a drug–target–pathway network that clarifies different mechanisms of treatment. The combination treatment of metformin and D-limonene induced apoptosis in both cell lines compared with single drug treatments, as indicated by flow cytometric and gene expression analysis. Results The mRNA expression of Bax and P53 genes were significantly upregulated while Bcl-2, iNOS, and Cox-2 were significantly downregulated in all treatment groups compared with normal cells. The percentages of late apoptotic HepG2 and MCF-7 cells were higher in all treatment groups, particularly in the combination treatment group. Calculations for the combination index (CI) revealed a synergistic effect between both drugs for HepG2 cells (CI = 0.14) and MCF-7 cells (CI = 0.22). Conclusion Our data show that metformin, D-limonene, and their combinations exerted significant antitumor effects on the cancer cell lines by inducing apoptosis and modulating the expression of apoptotic genes.

Background: Cancer is a fatal disease that severely affects humans. Designing new anticancer strategies and understanding the mechanism of action of anticancer agents is imperative. Hypothesis/Purpose: In this study, we evaluated the utility of metformin and D-limonene, alone or in combination, as potential anticancer therapeutics using the human liver and breast cancer cell lines HepG2 and MCF-7. Study design: An integrated systems pharmacology approach is presented for illustrating the molecular interactions between metformin and D-limonene. Methods: We applied a systems-based analysis to introduce a drug–target–pathway network that clarifies different mechanisms of treatment. The combination treatment of metformin and D-limonene induced apoptosis in both cell lines compared with single drug treatments, as indicated by flow cytometric and gene expression analysis. Results: The mRNA expression of Bax and P53 genes were significantly upregulated while Bcl-2, iNOS, and Cox-2 were significantly downregulated in all treatment groups compared with normal cells. The percentages of late apoptotic HepG2 and MCF-7 cells were higher in all treatment groups, particularly in the combination treatment group. Calculations for the combination index (CI) revealed a synergistic effect between both drugs for HepG2 cells (CI = 0.14) and MCF-7 cells (CI = 0.22). Conclusion: Our data show that metformin, D-limonene, and their combinations exerted significant antitumor effects on the cancer cell lines by inducing apoptosis and modulating the expression of apoptotic genes. [ABSTRACT FROM AUTHOR]

Boce Liu,1 Wenjing Wang,1 Jianhai Bi,2,* Ran Huo1,2,* 1Department of Plastic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianhai Bi, Department of Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China, Tel +86-15110080702, Fax +86 531-68778160, Email bijianhai@126.com Ran Huo, Department of Plastic Surgery, Shandong Provincial Hospital of Shandong University, Jinan, Shandong, People’s Republic of China, Tel +86-15168889001, Fax +86 531-68778153, Email huoran@medmail.com.cnAbstract: Follicular occlusion tetrad (FOT) is a chronic inflammatory skin disease that seriously affects patients’ quality of life. At present, there is no standard treatment plan for FOT. We report the case of a 50-year-old male patient diagnosed as having FOT with Fordyce granules and type 2 diabetes mellitus. During hospitalization, the patient received comprehensive and systematic treatment. The patient healed well after surgery and the 10-month follow-up revealed no recurrence. We found eight gene mutations by whole-exome sequencing (WES) of the patient’s peripheral blood.Keywords: follicular occlusion tetrad, Fordyce granules, gene analysis, comprehensive treatment

Polycystic ovarian syndrome (PCOS) is a commonly occurring reproductive disorder among the reproductive-aged women. Its global occurrence varies based on diagnostic guidelines, ethnicities, and locations of concern. Insulin resistance (IR) is commonly observed around 65–70% of women diagnosed with PCOS, representing a prevalent association. Consequently, the study was designed with an objective of illustrating the effect of insulin on mural and cumulus granulosa cells (GCs) of PCOS patients in comparison to normal ovulating women. This study is a case–control design, wherein a total of 80 participants were recruited meeting criterion of inclusion and exclusion, divided into 8 groups with each group consisting of 10 samples. The process involves the isolation and culturing of mural granulosa cells (MGC) and cumulus granulosa cells (CGC) with and without exposure to insulin. The proteins released by untreated GCs and insulin-treated GCs were extracted, and complex protein mixtures were digested with trypsin, followed by tandem mass spectrometry analysis and data processing using bioinformatics. We found 595 proteins in both control and PCOS samples, of which 310 were contributed by MGCs and 285 by CGCs. The PCOS MGCs expressed 20%, both the normal MGCs and CGCs have equal representation of 16% by each, whereas the PCOS CGCs proteins contributed 15% of the total of the proteomic expression. However, the poor expression observed with the Insulin exposure, the Insulin treated PCOS CGCs contributes 13%, PCOS MGCs contributes 8%. The normal MGCs upon the Insulin treatment give 8% then and there only 4% of proteins expressed by normal CGCs after Insulin treatment. The Venn analysis widened on their precise expression topographies. The examination of strings exhibited important protein–protein interaction pathways. This is a pioneering investigation aimed to establish the link between hyperinsulinemia in localized follicular GCs and PCOS mechanisms by comparing them to control group. The examination of various attributes, mechanisms, and traits shown by genes and proteins in individuals with PCOS compared to control populations, alongside the investigation of the dynamics of these genes and proteins following exposure to insulin, holds promise for the formulation of novel hypotheses and strategies in the identification of new biomarkers. [ABSTRACT FROM AUTHOR]

Abstract Background Juvenile polyposis syndrome (JPS), a rare autosomal dominant syndrome, affects one per 100 000 births, increasing lifetime cancer risk by 9 – 50%. Around 40–60% of JPS cases are caused by disease-causing variants (DCV) in SMAD4 or BMPR1A genes, of which SMAD4 accounts for 20–30%. Objectives To characterise genotype–phenotype correlations between sites and types of variants within SMAD4 to JPS phenotypes, to inform diagnosis, screening, and management of JPS. Search methods Online search databases utilised included Ovid MEDLINE, Embase Classic + Embase and PubMed, using search terms classified by MeSH on Demand. Adjacency operators, word truncation and Boolean operators were employed. 110 articles were included in the review, collating 291 variants from the literature. Results In SMAD4 + JPS patients, most variants are located around SMAD4’s MH2 domain (3’ end). Extracolonic involvement, massive gastric polyposis and a more aggressive phenotype have been associated with SMAD4 + JPS, predisposing to gastric cancer. This has contributed to an overall higher incidence of GI cancers compared to other genes causing JPS, with DCVs mostly all within the MH2 domain. Genetically related allelic disorders of SMAD4 also have variants in this region, including hereditary haemorrhagic telangiectasia (HHT) alongside SMAD4 + JPS, and Myhre syndrome, independent of JPS. Similarly, with DCVs in the MH2 domain, Ménétrier’s disease, hypertrophic osteoarthropathy and juvenile idiopathic arthritis have been seen in this population, whereas cardiac pathologies have occurred both alongside and independently of SMAD4 + JPS with DCVs in the MH1 domain. Conclusion Truncating and missense variants around the MH2 region of SMAD4 are most prevalent and pathogenic, thus should undergo careful surveillance. Given association with extracolonic polyposis and higher GI cancer risk, endoscopic screening should occur more frequently and at an earlier age in SMAD4 + JPS patients than in patients with other causative genes, with consideration of Ménétrier’s disease on upper GI endoscopy. In addition, HHT should be evaluated within 6 months of diagnosis, alongside targeted clinical examination for extraintestinal manifestations associated with SMAD4 + JPS. This review may help modify clinical diagnosis and management of SMAD4 + JPS patients, and aid pathogenicity classification for SMAD4 DCVs through a better understanding of the phenotypes.

Background: Spontaneous remission of cancer is a rare and poorly understood phenomenon characterized by complete or partial remission of a malignancy in the absence of or with inadequate treatment. The underlying mechanism for such occurrences is poorly understood, however, immune mechanisms seem to play an important role in such cases. In recent years increasingly more data have become available in favor of the clinical benefit of low levels of chimerism in hematologic malignancies. One such instance of naturally occurring low-level chimerism is feto-maternal microchimerism which has been shown to influence cancer progression and, in some instances, to be a protective factor against malignancy. Case report: We report a case of a young female patient with aggressive primary mediastinal large B cell lymphoma refractory to two lines of chemo-immunotherapy achieving sustained complete metabolic remission of tumor while pregnant with twins. Results: A focus on feto-maternal microchimerism during and after pregnancy revealed transient levels of feto-maternal microchimerism in the peripheral blood of the patient as measured by quantifying the Y-chromosome-linked SRY gene. Conclusions: Microchimerism presents significant potential for enhancing our comprehension of disease mechanisms, uncovering novel therapeutic targets, and refining diagnostic and treatment approaches, especially concerning cancer.

Background: Juvenile polyposis syndrome (JPS), a rare autosomal dominant syndrome, affects one per 100 000 births, increasing lifetime cancer risk by 9 – 50%. Around 40–60% of JPS cases are caused by disease-causing variants (DCV) in SMAD4 or BMPR1A genes, of which SMAD4 accounts for 20–30%. Objectives: To characterise genotype–phenotype correlations between sites and types of variants within SMAD4 to JPS phenotypes, to inform diagnosis, screening, and management of JPS. Search methods: Online search databases utilised included Ovid MEDLINE, Embase Classic + Embase and PubMed, using search terms classified by MeSH on Demand. Adjacency operators, word truncation and Boolean operators were employed. 110 articles were included in the review, collating 291 variants from the literature. Results: In SMAD4 + JPS patients, most variants are located around SMAD4's MH2 domain (3' end). Extracolonic involvement, massive gastric polyposis and a more aggressive phenotype have been associated with SMAD4 + JPS, predisposing to gastric cancer. This has contributed to an overall higher incidence of GI cancers compared to other genes causing JPS, with DCVs mostly all within the MH2 domain. Genetically related allelic disorders of SMAD4 also have variants in this region, including hereditary haemorrhagic telangiectasia (HHT) alongside SMAD4 + JPS, and Myhre syndrome, independent of JPS. Similarly, with DCVs in the MH2 domain, Ménétrier's disease, hypertrophic osteoarthropathy and juvenile idiopathic arthritis have been seen in this population, whereas cardiac pathologies have occurred both alongside and independently of SMAD4 + JPS with DCVs in the MH1 domain. Conclusion: Truncating and missense variants around the MH2 region of SMAD4 are most prevalent and pathogenic, thus should undergo careful surveillance. Given association with extracolonic polyposis and higher GI cancer risk, endoscopic screening should occur more frequently and at an earlier age in SMAD4 + JPS patients than in patients with other causative genes, with consideration of Ménétrier's disease on upper GI endoscopy. In addition, HHT should be evaluated within 6 months of diagnosis, alongside targeted clinical examination for extraintestinal manifestations associated with SMAD4 + JPS. This review may help modify clinical diagnosis and management of SMAD4 + JPS patients, and aid pathogenicity classification for SMAD4 DCVs through a better understanding of the phenotypes. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Bioprocess Engineering is the property of Chinese Journal of Bioprocess Engineering Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This work provides insights into the effect of fire on soil processes in Mediterranean-type ecosystems in Cyprus. Soil samples from mountainous sites that were subjected to a summer wildfire and adjacent control samples were collected. Incubations were used to estimate basal respiration and isolate soil CO2 release of heterotrophic microorganisms from autotrophic root respiration and heterotrophic respiration from litter decomposition. Physicochemical property changes, bacteria community changes using DNA extraction and 16S rRNA gene analysis, and the effects of ash and fresh litter addition were studied to reveal the microbial composition and the post-fire soil function. Laboratory incubation showed that burned soils constantly showed higher microbial respiration rates compared with control unburned areas, even six months after a fire. Adding ash to unburned samples increased microbial respiration, suggesting that increased nutrient availability positively corelates with the increased release of CO2 from fire-affected soil. Elevated temperatures due to the wildfire exerted significant effects on the composition of soil bacterial microbiota. Nevertheless, the wildfire did not affect the alpha-diversity of soil bacteria. New communities of microorganisms are still able to decompose fresh plant material after a fire, but at a slower rate than natural pre-fire populations.

Biomarker-based cancer identification and classification tools are widely used in bioinformatics and machine learning fields. However, the high dimensionality of microarray gene expression data poses a challenge for identifying important genes in cancer diagnosis. Many feature selection algorithms optimize cancer diagnosis by selecting optimal features. This article proposes an ensemble rank-based feature selection method (EFSM) and an ensemble weighted average voting classifier (VT) to overcome this challenge. The EFSM uses a ranking method that aggregates features from individual selection methods to efficiently discover the most relevant and useful features. The VT combines support vector machine, k-nearest neighbor, and decision tree algorithms to create an ensemble model. The proposed method was tested on three benchmark datasets and compared to existing built-in ensemble models. The results show that our model achieved higher accuracy, with 100% for leukaemia, 94.74% for colon cancer, and 94.34% for the 11-tumor dataset. This study concludes by identifying a subset of the most important cancer-causing genes and demonstrating their significance compared to the original data. The proposed approach surpasses existing strategies in accuracy and stability, significantly impacting the development of ML-based gene analysis. It detects vital genes with higher precision and stability than other existing methods. [ABSTRACT FROM AUTHOR]

The prediction of gene structure within the genome sequence is the starting point of genome analysis, and its accuracy has a significant impact on the quality of subsequent analyses. Gene structure prediction is roughly divided into RNA-Seq-based methods, ab initio -based methods, homology-based methods, and the integration of individual prediction methods. Integrated methods are mainstream in recent genome projects because they improve prediction accuracy by combining or taking the best individual prediction findings; however, adequate prediction accuracy for eukaryotic species has not yet been achieved. Therefore, we developed an integrated tool, GINGER, that solves various issues related to gene structure prediction in higher eukaryotes. By handling artefacts in alignments of RNA and protein sequences, reconstructing gene structures via dynamic programming with appropriately weighted and scored exon/intron/intergenic regions, and applying different prediction processes and filtering criteria to multi-exon and single-exon genes, we achieved a significant improvement in accuracy compared to the existing integration methods. The feature of GINGER is its high prediction accuracy at the gene and exon levels, which is pronounced for species with more complex gene architectures. GINGER is implemented using Nextflow, which allows for the efficient and effective use of computing resources. [ABSTRACT FROM AUTHOR]

Background: Congenital nephrotic syndrome (CNS) of the Finnish type (CNF) is an autosomal recessively disorder. NPHS1 gene mutation is the main gene responsible for CNF. This study aimed to explore the clinical manifestations and the characteristics of genetic variation in Chinese patients with CNS. Methods: A 15-minute-old boy and a 34-day-old girl with CNS were included. NPHS1 gene was detected by nextgeneration high-throughput sequencing. Results: Patient 1 carried two novel heterozygous mutations of NPHS1 gene, one was c.204delG, p. (Leu69fs) in exon 2 of NPHS1 gene, a heterozygote frameshift mutation; the other was c.3558delT, p. (Gly1187fs) in exon 28, a heterozygote frameshift mutation. Patient 2 carried three heterozygous mutations of NPHS1, among them, c.1561-G>A. p.Asp521Asn in exon 12 is a heterozygous missense mutation. It was identified as possible de novo pathogenicity gene. Conclusions: Three novel heterozygous mutations of NPHS1 gene were responsible for the patients with CNS and can enlarge the spectrum of NPHS1 gene mutation. [ABSTRACT FROM AUTHOR]

The Gene Ontology (GO) knowledge base provides a standardized vocabulary of GO terms for describing gene functions and attributes. It consists of three directed acyclic graphs which represent the hierarchical structure of relationships between GO terms. GO terms enable the organization of genes based on their functional attributes by annotating genes to specific GO terms. We propose an information-retrieval derived distance between genes by using their annotations. Four gene sets with causal associations were examined by employing our proposed methodology. As a result, the discovered homogeneous subsets of these gene sets are semantically related, in contrast to comparable works. The relevance of the found clusters can be described with the help of ChatGPT by asking for their biological meaning. The R package BIDistances, readily available on CRAN, empowers researchers to effortlessly calculate the distance for any given gene set. [ABSTRACT FROM AUTHOR]

Abstract Background The authors recently performed plastic surgeries for a small number of patients with hemophilia, HIV infection, and morphologic evidence of lipodystrophy. Because the pathophysiological mechanism of HIV-associated lipodystrophy remains to be elucidated, we analyzed subcutaneous adipose tissues from the patients. Methods All six patients had previously been treated with older nucleoside analogue reverse-transcriptase inhibitors (NRTIs; stavudine, didanosine or zidovudine). Abdominal and inguinal subcutaneous fat samples were obtained from the HIV+ patients with hemophilia and HIV− healthy volunteers (n = 6 per group), and analyzed via DNA microarray, real-time PCR, flow cytometry and immunohistochemistry. Results The time from initial NRTI treatment to collecting samples were 21.7 years in average. Cytometric analysis revealed infiltration of inflammatory M1 macrophages into HIV-infected adipose tissue and depletion of adipose-derived stem cells, possibly due to exhaustion following sustained adipocyte death. Genetic analysis revealed that adipose tissue from HIV+ group had increased immune activation, mitochondrial toxicity, chronic inflammation, progressive fibrosis and adipocyte dysfunction (e.g. insulin resistance, inhibited adipocyte differentiation and accelerated apoptosis). Of note, both triglyceride synthesis and lipolysis were inhibited in adipose tissue from patients with HIV. Conclusions Our findings provide important insights into the pathogenesis of HIV-associated lipodystrophy, suggesting that fat redistribution may critically depend on adipocytes’ sensitivity to drug-induced mitochondrial toxicity, which may lead either to atrophy or metabolic complications.

BackgroundShwachman-Diamond syndrome (SDS) is a rare autosomal recessive genetic disease that has complex and various clinical presentations. With the increase in application and clinical sensitivity of genome sequencing, the diagnoses of SDS in children and adults using genome sequencing have increased significantly, but most Chinese SDS patients have not received systematic and standardized treatment after diagnosis.ObjectiveTo analyze the clinical characteristics, diagnosis and treatment of three children with SDS, expecting to improve clinicians' recognition of this disease, reduce the possibilities of missed diagnosis and misdiagnosis, and standardize the treatment of diagnosed children.MethodsData of three children with SDS were collected from Department of Pediatrics, Peking University First Hospital from October 2018 to October 2020, including clinical manifestations, laboratory examination, gene analysis, treatment and follow-up, and were analyzed. In combination with the review of other relevant literature, the diagnosis and treatment of pediatric cases of SDS were summarized.ResultsAmong the three cases encountered and treated by us, two were female and one was male. All of them had recurrent infection, fatty diarrhea, short stature and malnutrition. Case 2 also had syndactyly. Auxiliary tests suggested that all these cases had neutropenia and abnormal liver function. Besides that, case 1 also had severe anemia, and case 2 had thrombocytopenia. Two compound heterozygous mutations of SBDS gene, that is, c.258 + 2T>C and c.184A>T, were found in all three cases. For treatment, all three patients were given pancreatic enzyme replacement therapy, nutritional support, and hepatoprotective treatment. The anemia of case 1, which was dependent on suspended red blood cell transfusion, was obviously improved after low-dose prednisone treatment.ConclusionSDS is a disease with multiple systems involved. Gene detection is helpful to the early diagnosis of SDS. Comprehensive, multidisciplinary treatment is needed. Hematopoietic stem cell transplantation with reduced dose pretreatment can improve some clinical manifestations, but the transplantation indications should be strictly controlled. Low dose and short course of glucocorticoid could be used to reduce the dependence on blood products for those with low erythropoiesis and no hematopoietic stem cell transplantation conditions.

Copyright of China Journal of Oral & Maxillofacial Surgery is the property of Shanghai Jiao Tong University, College of Stomatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Otosclerosis is one of the most common causes of hearing loss in young adults. It has a prevalence of 0.3–0.4% in the European population. Clinical symptoms usually occur between the second and fifth decade of life. Different studies have been performed to unravel the genetic architecture of the disease. Recently, a genome-wide association study (GWAS) identified 15 novel risk loci and replicated the regions of three previously reported candidate genes. In this study, seven candidate genes from the GWAS were resequenced using single molecule molecular inversion probes (smMIPs). smMIPs were used to capture the exonic regions and the 3′ and 5′ untranslated regions (UTR). Discovered variants were tested for association with the disease using single variant and gene-based association analysis. The single variant results showed that 13 significant variants were associated with otosclerosis. Associated variants were found in five of the seven genes studied here, including AHSG, LINC01482, MARK3, SUPT3H and RELN. Conversely, burden testing did not show a major role of rare variants in the disease. In conclusion, this study was able to replicate five out of seven candidate genes reported in the previous GWAS. This association is likely mainly driven by common variants. [ABSTRACT FROM AUTHOR]

Islet transplantation from organ donors can considerably improve glucose homeostasis and well‐being in individuals with type 1 diabetes, where the beta cells are destroyed by the autoimmune attack, but there are insufficient donor islets to make this a widespread therapy. Strategies are therefore being developed to generate unlimited amounts of insulin‐producing beta cells from pluripotent stem cells, with the aim that they will be transplanted to treat diabetes. Whilst much progress has been made in recent years in the directed differentiation of pluripotent stem cells to beta‐like cells, essential gaps still exist in generating stem cell‐derived beta cells that are fully functional in vitro. This short review provides details of recent multi‐'omics' studies of the human fetal pancreas, which are revealing granular information on the various cell types in the developing pancreas. It is anticipated that this fine mapping of the pancreatic cells at single‐cell resolution will provide additional insights that can be utilised to reproducibly produce human beta cells in vitro that have the functional characteristics of beta cells within native human islets. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound‐guided tissue acquisition (EUS‐TA) currently plays a central role in the diagnosis of pancreatic ductal adenocarcinoma (PDAC). Although fine‐needle aspiration has been the gold standard, novel biopsy needles for fine‐needle biopsy (FNB) were developed to overcome its limitations, which include low tumor cellularity and the inability to retain cellular architecture. Following recent improvements in FNB needles, the pathological diagnosis has shifted from cytology to histology and now to genetic diagnosis. Genetic analysis using EUS‐TA samples began with a search for the presence of K‐ras mutations. However, the introduction of next‐generation sequencers has dramatically changed genetic analysis and led to the gradual elucidation of the mechanism of PDAC, enabling personalized medicine by performing multiple gene analyses simultaneously. Comprehensive genomic profiling is currently applied in the clinical setting and there is an increasing need for gene analysis using EUS‐TA samples. Although target genome sequencing is feasible even with cytological specimens, it can be difficult to proceed with full genetic analysis including whole‐exome sequence or whole‐genome sequence if the samples are too small. Genetic analysis will become highly important in determining indications for personalized medicine such as poly (ADP‐ribose) polymerase inhibitors or immune checkpoint inhibitors. Therefore, the endosonographer must always take gene analysis into consideration when collecting samples for diagnosis and further improvement of the puncture technique and needle development are anticipated in the future. [ABSTRACT FROM AUTHOR]

The timber species Eucalyptus camaldulensis is one of the most important in southern China. Therefore, it is essential to understand the photosynthetic pattern in eucalyptus leaves. In the present study, eighteen photosynthesis-related genes were analyzed using bioinformatics methods. The results indicated that there were ten differentially expressed ribose-5-phosphate isomerase genes (RPI), and six of them were up-regulated in the mature leaves compared to the young leaves, while others were down-regulated. The differential expression of four rubisco methyltransferase genes (RBCMT) were observed. Two of them were up-regulated, while two were down-regulated in mature leaves compared to young leaves. Furthermore, two ribulose-phosphate-3-epimerase genes (RPE) were up-regulated in the mature leaves compared to the young leaves. In contrast, two genes involved in triosephosphate isomerase (TIM) were down-regulated in mature leaves compared with young leaves. The current study provides basic information about the transcriptome of E. camaldulensis and lays a foundation for further research in developing and utilizing important photosynthetic genes. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune progressive disease, associated with many pathophysiological consequences. Owing to the adverse effects and higher costs of pharmaceuticals, people are now looking for complementary and alternative remedies. In this milieu, the present study was designed to explore the therapeutic potential of walnuts against FCA‐induced arthritis in rat models. Purposely, 50 Sprague Dawley rats were housed in a well‐ventilated animal room and separated into 5 groups of 10 rats each. The rats were categorized as G0 (negative control), G1 (positive control, i.e., FCA induced untreated arthritic rats), G2 (arthritic rats treated with MTX), G3 (arthritic rats treated with walnut feed), and G4 (arthritic rats treated with walnut extract), with an efficacy trial lasting for 42 days. The physical analysis explicated that paw swelling was significantly improved by 10%–12.8% in treatment groups after the intervention when compared with positive control. Moreover, biochemical analyses revealed significantly lower levels of ESR, CRP, and RF in rats treated with walnut‐based interventions when compared to positive control. ESR values were decreased by 62.4% and 69.92% in G3 and G4, whereas CRP levels were improved by 56.20% and 77.78% in G3 and G4 when compared with G1. Likewise, RF values decreased in G2, G3, and G4 by 64.71%, 55.88%, and 69.24%, respectively when compared to G1. The histological examination demonstrated the potential role of walnut‐based interventions in reducing the severity of disease by decreasing cell infiltration, bone erosion, and paw inflammation. Meanwhile, the gene expression analysis revealed that walnut‐based interventions protected the paw joints from damage by downregulating the RANKL‐OPG pathway. Conclusively, walnut feed and extract may serve as potent anti‐arthritic interventions with no side effects. Practical applications: Plant‐based therapeutics are effective in the prevention and management of various chronic diseases. The current research explored the anti‐arthritic potential of walnuts. Walnut feed and extract effectively reduced the serum arthritic biomarkers as well as downregulated the genes involved in bone destruction. Thus, the inclusion of dietary ingredients having therapeutic potential such as walnuts may be synchronized in clinical practices to ameliorate arthritis. [ABSTRACT FROM AUTHOR]

Abstract Background Myelodysplastic syndromes (MDS) are clonal disorders of hematopoietic stem cells exhibiting ineffective hematopoiesis and tendency for transformation into acute myeloid leukemia (AML). The available karyotyping and fluorescent in situ hybridization provide limited information on molecular abnormalities for diagnosis/prognosis of MDS. Next generation DNA sequencing (NGS), providing deep insights into molecular mechanisms being involved in pathophysiology, was employed to study MDS in Pakistani cohort. Patients and methods It was a descriptive cross-sectional study carried out at National institute of blood diseases and bone marrow transplant from 2016 to 2019. Total of 22 cases of MDS were included. Complete blood counts, bone marrow assessment and cytogenetic analysis was done. Patients were classified according to revised WHO classification 2016 and IPSS score was applied for risk stratification. Baseline blood samples were subjected to analysis by NGS using a panel of 54 genes associated with myeloid malignancies. Results The median age of patients was 48.5 ± 9.19 years. The most common presenting complaint was weakness 10(45.45%). Cytogenetics analysis revealed abnormal karyotype in 10 (45.45%) patients. On NGS, 54 non-silent rare frequency somatic mutational events in 29 genes were observed (average of 3.82 (SD ± 2.08) mutations per patient), including mutations previously not observed in MDS or AML. Notably, two genes of cohesin complex, RAD21 and STAG2, and two tumor suppressor genes, CDKN2A and TP53, contained highest number of recurrent non-silent somatic mutations in the MDS. Strikingly, a missense somatic mutation p.M272Rof Rad21 was observed in 13 cases. Overall, non-silent somatic mutations in these four genes were observed in 21 of the 22 cases. The filtration with PharmGKB database highlighted a non-synonymous genetic variant rs1042522 [G > C] located in the TP53. Genotype GG and GC of this variant are associated with decreased response to cisplatin and paclitaxel chemotherapy. These two genotypes were found in 13 cases. Conclusion Sequencing studies suggest that numerous genetic variants are involved in the initiation of MDS and in the development of AML. In countries like Pakistan where financial reservation of patients makes the use of such analysis even more difficult when the availability of advanced techniques is already a prevailing issue, our study could be an initiating effort in adding important information to the local data. Further studies and large sample size are needed in future to enlighten molecular profiling and ultimately would be helpful to compare and contrast the molecular characteristics of Asian versus global population.

Melon (Cucumis melo L.) seed germination significantly affects its economic value. Cultivation of melon varieties with high germination ability and seedling vigor is beneficial in large-scale melon propagation. In this study, two melon genotypes differing in their germination ability, P5 with low and P10 with high germination ability, were used to identify the optimal seed germination conditions by evaluating different water immersion times and germination temperatures. The germination rate of the P5 and P10 parental genotypes and their segregating population, consisting of 358 F2: 3 families, were evaluated for 2 years to identify their genetic basis. QTL analysis was performed on a high-density geneticmap constructed using specific-locus amplified fragment sequencing (SLAF-seq). The germination rate of F1 and F2 populations treated with water immersion for 8 h at 28 °C and measured at 48 h showed a normal distribution Genetic mapping carried out using the high-density genetic map revealed eight QTLs in chromosomes 2, 4, 5, 6, and 8 that controlmelon seed germination, of which 2020/2021-qsg5.1 was consistently significant in both years of experimentation. qsg5.1 explained 15.13% of the phenotypic variance with a LOD of 4.1. To fine map the candidate region of qsg5.1, eight cleaved amplified polymorphism sequence (CAPS) markers were used to construct a genetic map with another 421 F2 individual fruits. The major QTL qsg5.1 was located between SNP53 and SNP54 within a 55.96 Kb interval containing four genes. qRT-PCR gene expression analysis of the candidate genes showed that MELO3C031219.2 (Phosphorus transporter PHO-5) exhibited a significant difference in gene expression between the parental lines at 24, 32, and 48 h after germination, potentially being the underlying gene controlling melon seed germination. These results provide a theoretical basis for the molecular mechanisms controlling melon seed germination and can practically contribute to further improving germination to increase the propagation effciency of commercial melon cultivars. [ABSTRACT FROM AUTHOR]

Background: Acute myocardial infarction (AMI) is one of the major causes of mortality and disability worldwide, and ischemic stroke (IS) is a serious complication after AMI. In particular, patients with ST-segment-elevation myocardial infarction (STEMI) are more susceptible to IS. However, the interrelationship between the two disease mechanisms is not clear. Using bioinformatics tools, we investigated genes commonly expressed in patients with STEMI and IS to explore the relationship between these diseases, with the aim of uncovering the underlying biomarkers and therapeutic targets for STEMI-associated IS. Methods: Differentially expressed genes (DEGs) related to STEMI and IS were identified through bioinformatics analysis of the Gene Expression Omnibus (GEO) datasets GSE60993 and GSE16561, respectively. Thereafter, we assessed protein-protein interaction networks, gene ontology term annotations, and pathway enrichment for DEGs using various prediction and network analysis methods. The predicted miRNAs targeting the co-expressed STEMI- and IS- related DEGs were also evaluated. Results: We identified 210 and 29 DEGs in GSE60993 and GSE16561, respectively. CD8A, TLR2, TLR4, S100A12, and TREM1 were associated with STEMI, while the hubgenes, IL7R, CCR7, FCGR3B, CD79A, and ITK were implicated in IS. In addition, binding of the transcripts of the co-expressed DEGsMMP9, ARG1, CA4, CRISPLD2, S100A12, andGZMK to their corresponding predicted miRNAs, especially miR-654-5p, may be associated with STEMI-related IS. Conclusions: STEMI and IS are related and MMP9, ARG1, CA4, CRISPLD2, S100A12, and GZMK genes may be underlying biomarkers involved in STEMI-related IS. [ABSTRACT FROM AUTHOR]

Background: Lysosomal storage disorders (LSDs) are a heterogeneous family of genetic diseases with a broad phenotypic spectrum. There is a paucity of data on LSDs from developing countries. Objective: We aimed to study the pattern, relative frequency, and phenotypic spectrum of LSDs in children at an Egyptian medical center. Patients and Methods: This study included children < 18 years with LSDs diagnosed and followed up at an Egyptian medical center from January 2018 to December 2021. Data were collected on patients’ demographics, clinical features, characteristic metabolites, specific enzyme assay, and genetic testing. Results: Forty-two children (62% males, 74% parental consanguinity and 26% positive family history) were diagnosed with 10 different LSDs, representing 14% of all cases with inborn errors of metabolism (IEMs). The most frequent LSDs groups were mucopolysaccharidosis (MPS) (52.4%) and sphingolipidosis (40.8%). The most common individual diseases were MPS I (26.2%), Gaucher disease (23.8), MPS III (16.7%), and acid sphingomyelinase deficiency (11.9%). The median age at presentation was two years with a median diagnostic delay of 12 months. The most common clinical manifestations were delayed development, intellectual disability, visceromegaly, coarse facial features, and skeletal abnormalities. Finally, genetic data were available for only 12 patients (8 Gaucher disease, 3 MPS-III, and 1 MPS-VI). Conclusion: LSDs (most commonly MPS and Gaucher disease) represent an important part of IEMs at our medical center, and the diagnosis seems challenging and often delayed. [ABSTRACT FROM AUTHOR]

Carnitine Acylcarnitine Translocase (CACT) deficiency and Carnitine Palmitoyl Transferase (CPT I and II) deficiency comes under a group of disorders called mitochondrial fatty acid oxidation disorders, due to defects in the carnitine cycle. The CPT and CACT enzymes play a pivotal role in the transfer of Long Chain Fatty Acids (LCFA) from the cytoplasm to the mitochondrial matrix, where β-oxidation take place. In the present case, a male baby presented on day 2 of life with chief complaints of respiratory distress, apnoea, lethargy and seizures. The baby had multiple episodes of hypoglycaemia and seizures after admission. Diagnosis was made with the help of extended newborn screening using Tandem Mass Spectrometry (TMS) showing accumulation of hexadecanoyl carnitine due to CACT/CPT II deficiency. Echocardiography showed features of cardiomyopathy with cardiomegaly. Liver Function Test (LFT) and Prothrombin Time-International Normalisation Ratio (PT-INR) of the child was also deranged, with hypotonia of all muscles. Early detection along with carnitine supplementation and further prevention of fasting episodes resulted in generalised improvement of the baby. So, a high degree of suspicion of Inborn Error of Metabolism (IEM) and timely diagnosis can save the baby

Fabry disease is an X-linked disorder of α-galactosidase A (GLA) deficiency. Our previous interim analysis (1 July 2014 to 31 December 2015) revealed plasma globotriaosylsphingosine as a promising primary screening biomarker for Fabry disease probands. Herein, we report the final results, including patients enrolled from 1 January to 31 December 2016 for evaluating the potential of plasma globotriaosylsphingosine and GLA activity as a combined screening marker. We screened 5691 patients (3439 males) referred from 237 Japanese specialty clinics based on clinical findings suggestive of Fabry disease using plasma globotriaosylsphingosine and GLA activity as primary screening markers, and GLA variant status as a secondary screening marker. Of the 14 males who tested positive in the globotriaosylsphingosine screen (≥2.0 ng/mL), 11 with low GLA activity (GLA variants (four classic, seven late-onset) and one with normal GLA activity and no pathogenic variant displayed lamellar bodies in affected organs, indicating late-onset biopsy-proven Fabry disease. Of the 19 females who tested positive in the globotriaosylsphingosine screen, eight with low GLA activity displayed GLA variants (six classic, two late-onset) and five with normal GLA activity displayed a GLA variant (one classic) and no pathogenic variant (four late-onset biopsy-proven). The combination of plasma globotriaosylsphingosine and GLA activity can be a primary screening biomarker for classic, late-onset, and late-onset biopsy-proven Fabry disease probands.

Carcinosarcoma, also known as malignant Mullerian mixed tumour, is a rare and aggressive ovarian malignant tumour. The prognosis of ovarian carcinosarcoma is very poor, accounting for the vast majority of ovarian cancer deaths. Due to the rarity of ovarian carcinosarcoma, no unified treatment plan exists at present. Here, we report the case of a 69-year-old patient with stage IC ovarian carcinosarcoma. She underwent right salpingo-oophorectomy and R0 resection, inclouding extrafascial hysterectomy, left salpingo-oophorectomy, omentectomy, appendectomy, right pelvic lymph node dissection and multipoint biopsy. Full-exome sequencing was performed with normal ovarian tissue, cancer tissue, sarcoma tissue and carcinosarcoma tissue, and the results showed that the sarcoma and carcinosarcoma tissue shared more mutated genes. A TP53 mutation occurred in the cancer tissue and carcinosarcoma tissue. By analysing the lychee tree, we found that the sarcoma tissue and carcinosarcoma tissue shared more subclones and determined that they were more closely related; the cancer tissue carried fewer subclones and was the main clone. The sarcoma may have evolved from the cancer tissues. Six rounds of postoperative chemotherapy (carboplatin + paclitaxel + ifosfamide (IFO) (paclitaxel 200 mg, D1 + carboplatin 600 mg, D1 + IFO 2G, D1-D3)) were administered. The patient has been followed up for six years and is currently in good health. In conclusion, the disease was diagnosed in the early stage, and the use of a R0 resection + a three-drug combination chemotherapy may have contributed to the patient's long-term disease-free survival. The results of the gene study suggested that the sarcoma component may be differentiated from the cancer component. We thus speculated that the origin of this case may have been the fallopian tube. [ABSTRACT FROM AUTHOR]

In recent years, soil salinization has become increasingly severe, and the ecological functions of saline–alkali soils have deteriorated because of the lack of plants. Therefore, understanding the tolerance mechanisms of saline–alkali-tolerant plants has become crucial to restore the ecological functions of saline–alkali soils. In this study, we evaluated the molecular mechanism underlying the tolerance of Kosteletzkya pentacarpos L. (seashore mallow) seedlings treated with 0.05 or 0.5% saline–alkali solution (NaCl: NaHCO3 = 4:1 mass ratio) for 1 and 7 days. We identified the key genes involved in tolerance to saline–alkali stress using orthogonal partial least squares regression analysis (OPLS-RA) based on both chlorophyll fluorescence indexes and stress-responsive genes using transcriptome analysis, and, finally, validated their expression using qRT-PCR. We observed minor changes in the maximum photochemical efficiency of the stressed seedlings, whose photosynthetic performance remained stable. Moreover, compared to the control, other indicators varied more evidently on day 7 of 0.5% saline–alkali treatment, but no variations were observed in other treatments. Transcriptome analysis revealed a total of 54,601 full-length sequences, with predominantly downregulated differentially expressed gene (DEG) expression. In the high concentration treatment, the expression of 89.11 and 88.38% of DEGs was downregulated on days 1 and 7, respectively. Furthermore, nine key genes, including KpAGO4 , KpLARP1C , and KpPUB33 , were involved in negative regulatory pathways, such as siRNA-mediated DNA methylation, inhibition of 5′-terminal oligopyrimidine mRNA translation, ubiquitin/proteasome degradation, and other pathways, including programmed cell death. Finally, quantitative analysis suggested that the expression of key genes was essentially downregulated. Thus, these genes can be used in plant molecular breeding in the future to generate efficient saline–alkali–tolerant plant germplasm resources to improve the ecological functions of saline–alkali landscapes. [ABSTRACT FROM AUTHOR]

Background Context: Hypertrophy of the ligamentum flavum (LF) is a major contributor to the development of lumbar spinal canal stenosis (LSS). Although previous studies have identified some factors related to hypertrophy of the LF, the etiology remains unclear. It is well known that myofibroblasts have a key role in the pathology of fibrosis in other tissues, including the skin, liver, kidney, and lung. We hypothesized that myofibroblasts were also important players in the pathology of fibrosis in the LF.Purpose: To elucidate the distribution and role of myofibroblasts in the hypertrophic LF.Study Design: A histological, immunohistochemical, and gene expression analysis of the LF in the human lumbar spine.Patient Sample: Hypertrophic LF tissue samples were collected from patients with LSS.Outcome Measures: Histology, immunohistochemistry, microarray, reverse transcription-quantitative polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay.Methods: The degree of fibrosis in the dural and dorsal layers of the LF was evaluated by Masson's trichrome tissue staining. Collagen gene expression was evaluated by quantitative reverse transcription polymerase chain reaction. Immunostaining of αSMA was performed to evaluate localization of myofibroblasts in LF tissue. The association between gene expression of alpha-smooth muscle actin (αSMA) and that of several types of collagen was investigated. The signal activated on the dorsal side of LF was examined by gene set enrichment analysis using microarray data. Expression levels of αSMA and several types of collagen in LF fibroblasts were investigated under hypoxic conditions.Results: In the histological study using Masson's trichrome staining, the fibrosis score was significantly higher in the dorsal layer than in the dural layer. Gene expression levels for several types of collagen (COL1A1, COL1A2, COL3A1, COL5A1, COL6A1, and COL11A1) and heat shock protein 47 (a collagen-specific chaperone) were significantly higher in the dorsal layer. Furthermore, immunohistochemistry revealed a significantly greater number of αSMA-stained cells in the dorsal layer. There was a strong correlation of αSMA mRNA expression with COL1A-1 in LF fibroblasts. Gene set enrichment analysis showed that the set of fibrosis-related gene signals, including those for epithelial-mesenchymal transition, hypoxia, and inflammation, were significantly upregulated in the dorsal layer compared with the dural layer. Under hypoxic stimulation, expression of αSMA and several types of collagen was increased in LF fibroblasts.Conclusions: This study is the first to reveal that myofibroblast expression levels are higher in the dorsal layer of the LF than in the dural layer. We confirmed that hypertrophy of the LF in LSS is associated with increased expression of myofibroblasts in the dorsal layer. Hypoxia could be a cause of expression of myofibroblasts leading to fibrosis and finally to hypertrophy of the LF.Clinical Significance: The results of this study partially elucidate the molecular mechanisms of LF hypertrophy and suggest that myofibroblasts may be involved in age-related degeneration of the LF. [ABSTRACT FROM AUTHOR]

In recent years, soil salinization has become increasingly severe, and the ecological functions of saline–alkali soils have deteriorated because of the lack of plants. Therefore, understanding the tolerance mechanisms of saline–alkali-tolerant plants has become crucial to restore the ecological functions of saline–alkali soils. In this study, we evaluated the molecular mechanism underlying the tolerance of Kosteletzkya pentacarpos L. (seashore mallow) seedlings treated with 0.05 or 0.5% saline–alkali solution (NaCl: NaHCO3 = 4:1 mass ratio) for 1 and 7 days. We identified the key genes involved in tolerance to saline–alkali stress using orthogonal partial least squares regression analysis (OPLS-RA) based on both chlorophyll fluorescence indexes and stress-responsive genes using transcriptome analysis, and, finally, validated their expression using qRT-PCR. We observed minor changes in the maximum photochemical efficiency of the stressed seedlings, whose photosynthetic performance remained stable. Moreover, compared to the control, other indicators varied more evidently on day 7 of 0.5% saline–alkali treatment, but no variations were observed in other treatments. Transcriptome analysis revealed a total of 54,601 full-length sequences, with predominantly downregulated differentially expressed gene (DEG) expression. In the high concentration treatment, the expression of 89.11 and 88.38% of DEGs was downregulated on days 1 and 7, respectively. Furthermore, nine key genes, including KpAGO4, KpLARP1C, and KpPUB33, were involved in negative regulatory pathways, such as siRNA-mediated DNA methylation, inhibition of 5′-terminal oligopyrimidine mRNA translation, ubiquitin/proteasome degradation, and other pathways, including programmed cell death. Finally, quantitative analysis suggested that the expression of key genes was essentially downregulated. Thus, these genes can be used in plant molecular breeding in the future to generate efficient saline–alkali–tolerant plant germplasm resources to improve the ecological functions of saline–alkali landscapes.

Background: The authors recently performed plastic surgeries for a small number of patients with hemophilia, HIV infection, and morphologic evidence of lipodystrophy. Because the pathophysiological mechanism of HIV-associated lipodystrophy remains to be elucidated, we analyzed subcutaneous adipose tissues from the patients. Methods: All six patients had previously been treated with older nucleoside analogue reverse-transcriptase inhibitors (NRTIs; stavudine, didanosine or zidovudine). Abdominal and inguinal subcutaneous fat samples were obtained from the HIV+ patients with hemophilia and HIV− healthy volunteers (n = 6 per group), and analyzed via DNA microarray, real-time PCR, flow cytometry and immunohistochemistry. Results: The time from initial NRTI treatment to collecting samples were 21.7 years in average. Cytometric analysis revealed infiltration of inflammatory M1 macrophages into HIV-infected adipose tissue and depletion of adipose-derived stem cells, possibly due to exhaustion following sustained adipocyte death. Genetic analysis revealed that adipose tissue from HIV+ group had increased immune activation, mitochondrial toxicity, chronic inflammation, progressive fibrosis and adipocyte dysfunction (e.g. insulin resistance, inhibited adipocyte differentiation and accelerated apoptosis). Of note, both triglyceride synthesis and lipolysis were inhibited in adipose tissue from patients with HIV. Conclusions: Our findings provide important insights into the pathogenesis of HIV-associated lipodystrophy, suggesting that fat redistribution may critically depend on adipocytes' sensitivity to drug-induced mitochondrial toxicity, which may lead either to atrophy or metabolic complications. [ABSTRACT FROM AUTHOR]

Background: Peripheral blood mononuclear cells (PBMCs) play an important role in the pathogenesis of pulmonary arterial hypertension (PAH). However, the specific roles of PBMCs in the development and progression of idiopathic PAH (IPAH) have not been fully understood. Methods: Here, differentially expressed genes (DEGs) of PBMCs or lung tissues between IPAH patients and healthy controls were identified via bioinformatics analysis of Gene Expression Omnibus (GEO) datasets GSE33463 and GSE48149, respectively. Subsequently, extensive target prediction and network analysis were performed to assess protein–protein interaction (PPI) networks, Gene Ontology (GO) terms, and pathway enrichment for DEGs. Co‐expressed DEGs between PBMCs and lung tissues coupled with corresponding predicted miRNAs involved in PAH were also assessed. We identified 251 DEGs in PBMCs and 151 DEGs in lung tissue samples from IPAH. PDK4, RBPMS2, and PDE5A expression were altered in both PBMCs and lung tissues from IPAH patients compared to healthy control. Results: CXCL8, JUN, TLR8, IL1B, and TLR7 could be implicated as the hub genes in PBMCs, whereas ENO1, STAT1, CXCL10, GPI, and IRF1 in lung tissues. Finally, co‐expressed DEGs of PDK4, RBPMS2, and PDE5A coupled with corresponding predicted miRNAs, especially miR‐103a‐3p, miR‐185‐5p, and miR‐515‐5p, are significantly associated with IPAH. Conclusion: Our findings collectively suggest that the expression levels of PDK4, RBPMS2, and PDE5A in PBMCs are associated with the expression of these genes in lung tissues. Thus, these molecules may serve as potential circulating biomarkers and/or possible therapeutic targets for IPAH. [ABSTRACT FROM AUTHOR]

Cutaneous melanoma is an aggressive cancer with increasing incidence and mortality rates worldwide. Metastasis is one of the primary elements that influence the prognosis of patients with cutaneous melanoma. This study aims to clarify the potential mechanism underlying the low survival rate of metastatic melanoma and to search for novel target genes to improve the survival rate of patients with metastatic tumors.

Abstract Background Peripheral blood mononuclear cells (PBMCs) play an important role in the pathogenesis of pulmonary arterial hypertension (PAH). However, the specific roles of PBMCs in the development and progression of idiopathic PAH (IPAH) have not been fully understood. Methods Here, differentially expressed genes (DEGs) of PBMCs or lung tissues between IPAH patients and healthy controls were identified via bioinformatics analysis of Gene Expression Omnibus (GEO) datasets GSE33463 and GSE48149, respectively. Subsequently, extensive target prediction and network analysis were performed to assess protein–protein interaction (PPI) networks, Gene Ontology (GO) terms, and pathway enrichment for DEGs. Co‐expressed DEGs between PBMCs and lung tissues coupled with corresponding predicted miRNAs involved in PAH were also assessed. We identified 251 DEGs in PBMCs and 151 DEGs in lung tissue samples from IPAH. PDK4, RBPMS2, and PDE5A expression were altered in both PBMCs and lung tissues from IPAH patients compared to healthy control. Results CXCL8, JUN, TLR8, IL1B, and TLR7 could be implicated as the hub genes in PBMCs, whereas ENO1, STAT1, CXCL10, GPI, and IRF1 in lung tissues. Finally, co‐expressed DEGs of PDK4, RBPMS2, and PDE5A coupled with corresponding predicted miRNAs, especially miR‐103a‐3p, miR‐185‐5p, and miR‐515‐5p, are significantly associated with IPAH. Conclusion Our findings collectively suggest that the expression levels of PDK4, RBPMS2, and PDE5A in PBMCs are associated with the expression of these genes in lung tissues. Thus, these molecules may serve as potential circulating biomarkers and/or possible therapeutic targets for IPAH.

Background: Cellular senescence is pivotal in the occurrence and progression of atrial fibrillation (AF). This study aimed to identify senescence-related genes that could be potential therapeutic biomarkers for AF., Methods: AF-related differentially expressed genes (DEGs) were identified using the Gene Expression Omnibus dataset. Weighted gene co-expression network analysis (WGCNA) was used to analyze important modules and potential hub genes. Integrating senescence-related genes, potential biomarkers were identified. Their differential expression levels were then validated in human atrial tissue, HL-1 cells, and Angiotensin II-infused mice. Finally, molecular docking analysis was conducted to predict potential interactions between potential biomarkers and the senolytic drug Navitoclax., Results: We identified seven genes common to AF-related DEGs and senescence-related genes. Three significant modules were selected from WGCNA analysis. Taken together, three senescence-related genes (ETS1, SP1, and WT1) were found to be significantly associated with AF. Protein-protein interaction network analysis revealed biological connections among the predicted target genes of ETS1, SP1, and WT1. Notably, ETS1, SP1, and WT1 exhibited significant differential expression in clinical samples as well as in vitro and in vivo models. Molecular docking revealed favorable binding affinity between senolytic Navitoclax and these potential biomarkers., Conclusions: This study highlights ETS1, SP1, and WT1 as crucial senescence-related genes associated with AF, offering potential therapeutic targets, with supportive evidence of binding affinity with senolytic Navitoclax. These findings provide novel insights into AF pathogenesis from a senescence perspective., Competing Interests: The authors have no competing interests to declare., (© 2024 The Authors.)

Background: Myelodysplastic syndromes (MDS) are clonal disorders of hematopoietic stem cells exhibiting ineffective hematopoiesis and tendency for transformation into acute myeloid leukemia (AML). The available karyotyping and fluorescent in situ hybridization provide limited information on molecular abnormalities for diagnosis/prognosis of MDS. Next generation DNA sequencing (NGS), providing deep insights into molecular mechanisms being involved in pathophysiology, was employed to study MDS in Pakistani cohort. Patients and methods: It was a descriptive cross-sectional study carried out at National institute of blood diseases and bone marrow transplant from 2016 to 2019. Total of 22 cases of MDS were included. Complete blood counts, bone marrow assessment and cytogenetic analysis was done. Patients were classified according to revised WHO classification 2016 and IPSS score was applied for risk stratification. Baseline blood samples were subjected to analysis by NGS using a panel of 54 genes associated with myeloid malignancies. Results: The median age of patients was 48.5 ± 9.19 years. The most common presenting complaint was weakness 10(45.45%). Cytogenetics analysis revealed abnormal karyotype in 10 (45.45%) patients. On NGS, 54 non-silent rare frequency somatic mutational events in 29 genes were observed (average of 3.82 (SD ± 2.08) mutations per patient), including mutations previously not observed in MDS or AML. Notably, two genes of cohesin complex, RAD21 and STAG2, and two tumor suppressor genes, CDKN2A and TP53, contained highest number of recurrent non-silent somatic mutations in the MDS. Strikingly, a missense somatic mutation p.M272Rof Rad21 was observed in 13 cases. Overall, non-silent somatic mutations in these four genes were observed in 21 of the 22 cases. The filtration with PharmGKB database highlighted a non-synonymous genetic variant rs1042522 [G > C] located in the TP53. Genotype GG and GC of this variant are associated with decreased response to cisplatin and paclitaxel chemotherapy. These two genotypes were found in 13 cases. Conclusion: Sequencing studies suggest that numerous genetic variants are involved in the initiation of MDS and in the development of AML. In countries like Pakistan where financial reservation of patients makes the use of such analysis even more difficult when the availability of advanced techniques is already a prevailing issue, our study could be an initiating effort in adding important information to the local data. Further studies and large sample size are needed in future to enlighten molecular profiling and ultimately would be helpful to compare and contrast the molecular characteristics of Asian versus global population. [ABSTRACT FROM AUTHOR]