Impacts of continuous cropping on the rhizospheric and endospheric microbial communities and root exudates of Astragalus mongholicus.

Astragalus mongholicus is a medicinal plant that is known to decrease in quality in response to continuous cropping. However, the differences in the root-associated microbiome and root exudates in the rhizosphere soil that may lead to these decreases are barely under studies. We investigated the plant biomass production, root-associated microbiota, and root exudates of A. mongholicus grown in two different fields: virgin soil (Field I) and in a long-term continuous cropping field (Field II). Virgin soil is soil that has never been cultivated for A. mongholicus. Plant physiological measurements showed reduced fresh and dry weight of A. mongholicus under continuous cropping conditions (i.e. Field II). High-throughput sequencing of the fungal and bacterial communities revealed differences in fungal diversity between samples from the two fields, including enrichment of potentially pathogenic fungi in the roots of A. mongholicus grown in Field II. Metabolomic analysis yielded 20 compounds in A. mongholicus root exudates that differed in relative abundance between rhizosphere samples from the two fields. Four of these metabolites (2-aminophenol, quinic acid, tartaric acid, and maleamate) inhibited the growth of A. mongholicus, the soil-borne pathogen Fusarium oxysporum, or both. This comprehensive analysis enhances our understanding of the A. mongholicus microbiome, root exudates, and interactions between the two in response to continuous cropping. These results offer new information for future design of effective, economical approaches to achieving food security.

Neuroprotective effect of ketamine and sevoflurane against TNF-α induced cognitive impairment.

In the present study, neuroprotective effect of sevoflurane in combination with ketamine was investigated on TNF-α induced necroptosis of neurons and cognitive impairment in the rat model. The results demonstrated that exposure to TNF-α/z-VAD led to a significant decrease in viability of HT-22 neuronal cells. However, incubation of HT-22 cells with ketamine plus sevoflurane inhibited decrease in viability induced by TNF-α/z-VAD exposure. The increase in production of ROS by TNF-α/z-VAD exposure in HT-22 cells was effectively suppressed on pre-treatment with ketamine plus sevoflurane. Moreover, suppression of TNF-α/z-VAD induced ROS production in HT-22 cells by ketamine plus sevoflurane pretreatment was higher in comparison to ketamine or sevoflurane treatment alone. Treatment of HT-22 cells with ketamine plus sevoflurane suppressed TNF-α/z-VAD induced increase in RIP1 and p-MLKL protein expression. Ketamine plus sevoflurane treatment effectively reversed decrease in movement speed as well as total distance traveled in TNF-α injected rats. The number of neurons in rat hippocampus injected with TNF-α showed a significant decrease more specifically in carbonic anhydrase-3 region. However, no significant change in the density of neurons was observed in the hippocampus of rats pretreated with ketamine plus sevoflurane by TNF-α injection. The increase in expression of p-MLKL and p-RIP3 by TNF-α injection was effectively reversed in rats on treatment with ketamine plus sevoflurane. In silico studies revealed that ketamine interacts with p-MLKL protein in different confirmations with the binding affinities ranging from -9.7 to -8.4 kcal/mol. It was found that ketamine binds to p-MLKL protein by interacting with alanine (ALA A:295), proline (PRO A:306), glutamine (GLN A: 307) and isoleucine (ILE A:293) amino acid residues. In summary, ketamine plus sevoflurane combination alleviates TNF-α/z-VAD induced decrease in viability of HT-22 cells in vitro and rat hippocampus neurons in vivo. Moreover, ketamine plus sevoflurane combination prevented TNF-α injection induced cognitive impairment in rats. Therefore, sevoflurane plus ketamine combination can be developed as a potential therapeutic regimen for treatment of isoflurone induced cognitive impairment.

First Report of Fusarium avenaceum Causing Root Rot of Raspberry (Rubus corchorifolius) in China.

Raspberry (Rubus corchorifolius) plants hold historical, economic, and medicinal importance in China (Yang et al. 2022). Raspberries are cultivated to generate income for local farmers in Lintao County, Dingxi City, Gansu Province. However, farmers encountered challenges due to raspberry plants exhibiting root rot disease, resulting in plant death. During a thorough field survey conducted in June 2022, symptoms ranging from leaf yellowing and wilting to necrotic lesions and root rots were observed, where approximately 30% of raspberry plants were affected. Five diseased and healthy plants were collected from the farmers' fields in Lintao (35.53oN, 103.84oE) for pathogen identification. Symptomatic and asymptomatic root tissues were surface sterilized with 75% ethanol for 30 s and 3% NaOCl for 5 min, followed by three rinses in sterile water. Small pieces (0.5 × 0.5 cm) were cut and incubated on potato dextrose agar (PDA) plates at 25°C for 7-10 days. Twenty-two pure Fusarium isolates, which displayed four distinct colony groups morphologically, were obtained. Pathogenicity tests on isolates RB10, RB1, RB30, and RB23, representing each colony group, revealed that RB10 exhibited symptoms similar to those observed in the field. The RB10 strain produced yellowish-white to greyish-white colonies on PDA and was then cultured in a carboxymethylcellulose (CMC) broth for enhanced conidia production (Zhang et al. 2020). Macroconidia were sickle-shaped or slightly curved, with three to five septa (19.2 to 38.5 x 3.1 to 5.8 µm, n =40). Microconidia were oval to ellipsoidal, non-septate or featuring 1 to 2 septa (4.8 to 10.5 x 2.1 to 5.2 µm, n=20). These morphological features indicated the isolate was similar to Fusarium avenaceum (Leslie and Summerell, 2006). For further identification of the strains, genomic regions (ITS-rDNA, TEF-1α, and RPB2) were amplified and sequenced using specific primers ITS1/ITS4, EF-1/EF-2, and 5f2/7cr, respectively (O'Donnell et al. 2010; Uwaremwe et al. 2021; Zarrin et al. 2016). PCR BLASTn queries of NCBI GenBank revealed a 99.8% (522 bp), 99.4% (355 bp) and 99.6% (985 bp) homology with F. avenaceum (MZ724839.1, MN271631.1, and MK185026.1), respectively. Sequences were deposited in GenBank (ITS, OR735571; TEF-1α, PP216660; RPB2, PP857820). One-year-old raspberry seedlings were planted in pots with a sterile soil mix (2:2:1 v/v ratio of soil, peat, and vermiculite) under controlled greenhouse conditions (23-26°C, 16h light/8h dark). A month post-planting, taproots were wounded in six pots and inoculated with 20 ml of conidia suspension (106 conidia/ml), while the other six pots were maintained as controls. After 14 days, RB10-infected plants showed symptoms similar to field observations, while controls remained healthy. The experiment was conducted twice, and re-isolation confirmed both the pathogenicity and identity of the pathogen. In the concatenated phylogenetic tree of ITS, TEF-1α and RPB2, strain RB10 was clustered with the F. avenaceum representative strains KG502, KG431 and F094. Studies revealed F. avenaceum varied pathogenicity across plants (Bugingo, 2022; Moparthi et al. 2020& 2024; Yli-Mattila et al. 2018), and it has been reported to induce raspberry fruit rot (Wang et al. 2017). However, no previous reports linked this fungus to raspberry root rot. This report is crucial for understanding the impact of root rot disease on raspberry cultivation and developing effective management strategies.

Targeted therapy using larotrectinib and venetoclax for the relapsed/refractory T-cell acute lymphoblastic leukemia harboring a cryptic ETV6-NTRK3 fusion.

Outcomes for patients with relapsed and refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are dismal, with few available treatments. Recently, identification of cancer patients harboring neurotrophic tropomyosin receptor kinase (NTRK) gene fusions is constantly increasing, especially with the advent of NTRK inhibitors. However, the role of ETV6-NTRK3 in T-ALL has not been investigated. This case represented the first detailed report of T-ALL patient harboring a cryptic ETV6-NTRK3 fusion with an unfavorable prognosis, not only because of leukemia resistant to the standard multiagent chemotherapy but also early relapse after allo-HSCT. Acquired EP300 mutation was found at relapse, which could explain the cause of recurrence and affect the follow-up treatment. Combined targeted therapy like larotrectinib allied with pan-targeted BCL-2 inhibitor venetoclax, may be a potential maintenance treatment in R/R ETV6-NTRK3 positive leukemia after allo-HSCT. The leukemic clonal evolution might be revealed through transcriptome sequencing and overcome by drugs with universal targets. Our case demonstrated that both comprehensive profiling techniques (such as transcriptome sequencing, multiparameter flow cytometry, and digital droplet polymerase chain reaction) and a multimodality treatment strategy were critical for anticipating an early relapse and personalized therapy of R/R T-cell leukemia.

Regulation of whole-transcriptome sequencing expression in COPD after personalized precise exercise training: a pilot study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the world's leading causes of death and a major chronic respiratory disease. Aerobic exercise, the cornerstone of pulmonary rehabilitation, improves prognosis of COPD patients; however, few studies have comprehensively examined the changes in RNA transcript levels and the crosstalk between various transcripts in this context. This study identified the expression of RNA transcripts in COPD patients who engaged in aerobic exercise training for 12 weeks, and further constructions of the possible RNAs networks were made. METHODS: Peripheral blood samples for all four COPD patients who benefited from 12 weeks of PR were collected pre- and post-aerobic exercises and evaluated for the expression of mRNA, miRNA, lncRNA, and circRNA with high-throughput RNA sequencing followed by GEO date validation. In addition, enrichment analyses were conducted on different expressed mRNAs. LncRNA-mRNA and circRNA-mRNA coexpression networks, as well as lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA competing expression networks (ceRNAs) in COPD were constructed. RESULTS: We identified and analyzed the differentially expressed mRNAs and noncoding RNAs in the peripheral blood of COPD patients' post-exercise. Eighty-six mRNAs, 570 lncRNAs, 8 miRNAs, and 2087 circRNAs were differentially expressed. Direct function enrichment analysis and Gene Set Variation Analysis showed that differentially expressed RNAs(DE-RNAs) correlated with several critical biological processes such as chemotaxis, DNA replication, anti-infection humoral response, oxidative phosphorylation, and immunometabolism, which might affect the progression of COPD. Some DE-RNAs were validated by Geo databases and RT-PCR, and the results were highly correlated with RNA sequencing. We constructed ceRNA networks of DE-RNAs in COPD. CONCLUSIONS: The systematic understanding of the impact of aerobic exercise on COPD was achieved using transcriptomic profiling. This research offers a number of potential candidates for clarifying the regulatory mechanisms that exercise has on COPD, which could ultimately help in understanding the pathophysiology of COPD.

A novel diagnostic approach for the classification of small B-cell lymphoid neoplasms based on the NanoString platform.

Small B-cell lymphoid neoplasms (SBCLNs) are a heterogeneous group of diseases characterized by malignant clonal proliferation of mature B-cells. However, the classification of SBCLNs remains a challenge, especially in cases where histopathological analysis is unavailable or those with atypical laboratory findings or equivocal pathologic data. In this study, gene expression profiling of 1039 samples from 27 gene expression omnibus (GEO) datasets was first investigated to select highly and differentially expressed genes among SBCLNs. Samples from 57 SBCLN cases and 102 nonmalignant control samples were used to train a classifier using the NanoString platform. The classifier was built by employing a cascade binary classification method based on the random forest algorithm with 35 refined gene signatures. Cases were successively classified as chronic lymphocytic leukemia/small lymphocytic lymphoma, conventional mantle cell lymphoma, follicular lymphoma, leukemic non-nodal mantle cell lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia, and other undetermined. The classifier algorithm was then validated using an independent cohort of 197 patients with SBCLNs. Under the distribution of our validation cohort, the overall sensitivity and specificity of proposed algorithm model were >95%, respectively, for all the cases with tumor cell content greater than 0.72. Combined with additional genetic aberrations including IGH-BCL2 translocation, MYD88 L265P mutation, and BRAF V600E mutation, the optimal sensitivity and specificity were respectively found at 0.88 and 0.98. In conclusion, the established algorithm demonstrated to be an effective and valuable ancillary diagnostic approach for the sub-classification and pathologic investigation of SBCLN in daily practice.

CircKIF4A enhances osteosarcoma proliferation and metastasis by sponging MiR-515-5p and upregulating SLC7A11.

BACKGROUND: Circular RNAs (circRNAs) are forms of non-coding RNAs that have crucial roles in regulation of various biological processes of several malignant tumors. circKIF4A is closely associated with malignant progression of a variety of cancers. However, the molecular mechanisms as well as roles of circKIF4A in osteosarcoma (OS) have not yet been clearly elucidated. METHODS: We evaluated the expression of circKIF4A in OS. Colony-formation, cell counting kit-8 (CCK-8), transwell and mice metastasis model assays were done to explore the roles of circKIF4A in vitro and in vivo. TargetScan database, double luciferase, quantitative reverse transcription polymerase chain reaction analysis (RT-qPCR), and RNA immunoprecipitation (RIP) were done to investigate the associated molecular mechanisms. RESULTS: In both OS cells and tissues, circKIF4A (hsa_circ_0007255) was found to be upregulated. In vitro and in vivo, circKIF4A knockdown markedly suppressed OS proliferation as well as metastasis. circKIF4A enhanced OS growth as well as metastasis by sponging miR-515-5p and by upregulating SLC7A11. CONCLUSIONS: We identified the biological significance of the circKIF4A-miR-515-5p-SLC7A11 axis in OS cell proliferation and metastasis, which is important in OS monitoring and treatment. More studies on circKIF4A will inform on the diagnostic markers for early OS screening.

Effects of Structural and Compositional Changes of Nanochloropsis oceania after Enzyme Treatment on EPA-Rich Lipids Extraction.

Improved methods for the extraction of eicosapentaenoic acid (EPA), an essential and economically important polyunsaturated fatty acid, are urgently required. However, lipid extraction rates using food-grade solvents such as ethanol are usually low. To improve the ethanol-based extraction rate, and to elucidate the relevant mechanisms, we used cellulase and laccase to treat powdered Nannochloropsis, one of the most promising microalgal sources of EPA. Cellulase and laccase synergistically increased lipid yields by 69.31% and lipid EPA content by 42.63%, by degrading the amorphous hemicellulose and cellulose, improving crystallinity, and promoting the release and extraction of lysodiacylglyceryltrimethylhomoserine. Scanning electron microscopy showed that cell morphology was substantially altered, with cell-wall rupture, loss of cell boundaries, and the release of intracellular substances. In conclusion, Nannochloropsis lipid yields may be directly linked to cell-wall hemicellulose structure, and enzymatic treatment to alter this may improve lipid yields.

LncRNA SNHG16 promotes pulmonary fibrosis by targeting miR-455-3p to regulate the Notch2 pathway.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung diseases with a poor prognosis. Long non-coding RNAs (lncRNAs) have been reported to be involved in IPF in several studies. However, the role of lncRNA SNHG16 in IPF is largely unknown. METHODS: Firstly, experimental pulmonary fibrosis model was established by using bleomycin (BML). Histology and Western blotting assays were used to determine the different stages of fibrosis and expression of several fibrosis biomarkers. The expression of SNHG16 was detected by quantitative real-time polymerase chain reaction (qRT-PCR). EdU staining and wound-healing assay were utilized to analyze proliferation and migration of lung fibroblast cells. Molecular mechanism of SNHG16 was explored by bioinformatics, dual-luciferase reporter assay, RNA immunoprecipitation assay (RIP), and qRT-PCR. RESULTS: The expression of SNHG16 was significantly up-regulated in bleomycin-(BLM) induced lung fibrosis and transforming growth factor-ß (TGF-ß)-induced fibroblast. Knockdown of SNHG16 could attenuate fibrogenesis. Mechanistically, SNHG16 was able to bind and regulate the expression of miR-455-3p. Moreover, SNHG16 also regulated the expression of Notch2 by targeting miR-455-3p. Finally, SNHG16 could promote fibrogenesis by regulating the expression of Notch2. CONCLUSION: Taken together, our study demonstrated that SNHG16 promoted pulmonary fibrosis by targeting miR-455-3p to regulate the Notch2 pathway. These findings might provide a novel insight into pathologic process of lung fibrosis and may provide prevention strategies in the future.

Biophysical characterization of oligomerization and fibrillization of the G131V pathogenic mutant of human prion protein.

The pathogenesis of fatal neurodegenerative prion diseases is closely associated with the conversion of α-helix-rich cellular prion protein into ß-sheet-rich scrapie form. Pathogenic point mutations of prion proteins usually promote the conformational conversion and trigger inherited prion diseases. The G131V mutation of human prion protein (HuPrP) was identified to be involved in Gerstmann-Sträussler-Scheinker syndrome. Few studies have been carried out to address the pathogenesis of the G131V mutant. Here, we addressed the effects of the G131V mutation on oligomerization and fibrillization of the full-length HuPrP(23-231) and truncated HuPrP(91-231) proteins. The G131V mutation promotes the oligomerization but alleviates the fibrillization of HuPrP, implying that the oligomerization might play a crucial role in the pathogenic mechanisms of the G131V mutant. Moreover, the flexible N-terminal fragment in either the wild-type or the G131V mutant HuPrP increases the oligomerization tendencies but decreases the fibrillization tendencies. Furthermore, this mutation significantly alters the tertiary structure of human PrPC and might distinctly change the conformational conversion tendency. Interestingly, both guanidine hydrochloride denaturation and thermal denaturation experiments showed that the G131V mutation does not significantly change the thermodynamic stabilities of the HuPrP proteins. This work may be of benefit to a mechanistic understanding of the conformational conversion of prion proteins and also provide clues for the prevention and treatment of prion diseases.

TTF1, in the Form of Nanoparticles, Inhibits Angiogenesis, Cell Migration and Cell Invasion In Vitro and In Vivo in Human Hepatoma through STAT3 Regulation.

TTF1-NP (5,2',4'-trihydroxy-6,7,5'-trimethoxyflavone nanoparticles), derived from the traditional Changbai Mountain medicinal plant Sorbaria sorbifolia (SS), has been showed its anti-cancer effect in various liver cancer cell types and tissues. The present study was designed to evaluate the antitumor mechanism of the TTF1-NP against HepG2 hepatoma cells and HepG2 cells-induced hepatocarcinoma (HCC) in nude mouse model. Here we demonstrated that TTF1-NP inhibits tube formation of HUVECs and HepG2 cell migration and invasion, and inhibits tumor growth in nude mice implanted with HepG2 cells through the downregulation of STAT3 protein and activation, along with VEGF, KDR, bFGF, MMP2 and MMP9 levels. We further revealed that TTF1-NP decreased the DNA-binding capacity of STAT3. Together our results provide a mechanism by which TTF1-NP suppresses cancer cell migration, invasion and angiogenesis through the action of STAT3 and suggests TTF1-NP as a potential therapy for hepatocellular cancer treatment.

[Apoptosis of human hepatocellular carcinoma HepG-2 cells upon inhibition of STAT3 by 5,2',4'-trihydroxy-6,7,5'-trimethoxy flavone nanoparticle].

This study was designed to investigate the mechanism of 5,2',4'-trihydroxy-6,7,5'-trimethoxy flavone nanoparticle (TTF1-NP) in the induction of apoptosis of human hepatocellular carcinoma HepG-2 cells. MTT assay, immunocytochemical staining and flow cytometry with Annexin V-FITC/PI were used to demonstrate inhibition of proliferation of HepG-2 cells and cell apoptosis. The inhibition was studied in a dose- and time-dependent manner. Western blot results showed that TTF1-NP down-regulated the signals of survivin, p-STAT3 and STAT3, but up-regulated the expression level of cleaved caspase-3. Taken together, our results showed that TTF1-NP induced HepG-2 cell apoptosis through inhibition of the STAT3 expression.

The Role of LMP1 in Epstein-Barr Virus-associated Gastric Cancer.

EBV promotes many cancers such as lymphoma, nasopharyngeal carcinoma, and gastric; Latent Membrane Protein 1 (LMP1) is considered to be a major oncogenic protein encoded by Epstein- Barr virus (EBV). LMP1 functions as a carcinogen in lymphoma and nasopharyngeal carcinoma, and LMP1 may also promote gastric cancer. The expression level of LMP1 in host cells is a key determinant in tumorigenesis and maintenance of virus specificity. By promoting cell immortalization and cell transformation, promoting cell proliferation, affecting immunity, and regulating cell apoptosis, LMP1 plays a crucial tumorigenic role in epithelial cancers. However, very little is currently known about LMP1 in Epstein-Barr virus-associated gastric cancer (EBVaGC); the main reason is that the expression level of LMP1 in EBVaGC is comparatively lower than other EBV-encoded proteins, such as The Latent Membrane Protein 2A (LMP2A), Epstein-Barr nuclear antigen 1 (EBNA1) and BamHI-A rightward frame 1 (BARF1), to date, there are few studies related to LMP1 in EBVaGC. Recent studies have demonstrated that LMP1 promotes EBVaGC by affecting The phosphatidylinositol 3-kinase- Akt (PI3K-Akt), Nuclear factor-kappa B (NF-κB), and other signaling pathways to regulate many downstream targets such as Forkhead box class O (FOXO), C-X-C-motif chemokine receptor (CXCR), COX-2 (Cyclooxygenase-2); moreover, the gene methylation induced by LMP1 in EBVaGC has become one of the characteristics that distinguish this gastric cancer (GC) from other types of gastric cancer and LMP1 also promotes the formation of the tumor microenvironment (TME) of EBVaGC in several ways. This review synthesizes previous relevant literature, aiming to highlight the latest findings on the mechanism of action of LMP1 in EBVaGC, summarize the function of LMP1 in EBVaGC, lay the theoretical foundation for subsequent new research on LMP1 in EBVaGC, and contribute to the development of novel LMP1-targeted drugs.

Energy metabolism: a new target for gastric cancer treatment.

Gastric cancer is the fifth most common malignancy worldwide having the fourth highest mortality rate. Energy metabolism is key and closely linked to tumour development. Most important in the reprogramming of cancer metabolism is the Warburg effect, which suggests that tumour cells will utilise glycolysis even with normal oxygen levels. Various molecules exert their effects by acting on enzymes in the glycolytic pathway, integral to glycolysis. Second, mitochondrial abnormalities in the reprogramming of energy metabolism, with consequences for glutamine metabolism, the tricarboxylic acid cycle and oxidative phosphorylation, abnormal fatty acid oxidation and plasma lipoprotein metabolism are important components of tumour metabolism. Third, inflammation-induced oxidative stress is a danger signal for cancer. Fourth, patterns of signalling pathways involve all aspects of metabolic transduction, and many clinical drugs exert their anticancer effects through energy metabolic signalling. This review summarises research on energy metabolism genes, enzymes and proteins and transduction pathways associated with gastric cancer, and discusses the mechanisms affecting their effects on postoperative treatment resistance and prognoses of gastric cancer. We believe that an in-depth understanding of energy metabolism reprogramming will aid the diagnosis and subsequent treatment of gastric cancer.

Salinity decreases the contribution of microbial necromass to soil organic carbon pool in arid regions.

Saline soils are widely distributed in arid areas but there is a lack of mechanistic understanding on the effect of salinity on the formation and biochemical composition of soil organic carbon (SOC). We investigated the effects of salinity on the accumulation of microbial necromass under natural vegetation and in cropland in salt-affected arid areas stretching over a 1200-km transect in northwest China. Under both natural vegetation and cropland, microbial physiological activity (indicated by microbial biomass carbon normalized enzymatic activity) decreased sharply where the electrical conductivity approached 4 ds m-1 (a threshold to distinguish between saline and non-saline soils), but microbial biomass was only slightly affected by salinity. These indicated that a larger proportion of microbes could be inactive or dormant in saline soils. The contribution of fungal necromass C to SOC decreased but the contribution of bacterial necromass C to the SOC increased with increasing soil salinity. Adding fungal and bacterial necromass C together, the contribution of microbial necromass C to SOC in saline soils was 32-39 % smaller compared with non-saline soils. Fungal necromass C took up 85-86 % of microbial necromass C in non-saline soils but this proportion dropped to 60-66 % in saline soils. We suggested that the activity, growth, and turnover rate of microbes slowed by salinity was responsible for the decreased accumulation of fungal necromass in saline compared with non-saline soils, while the increased accumulation of bacterial residue in saline soils could be induced mainly by its slower decomposition. Soil microbial biomass was a poor predictor for the accumulation of microbial necromass in saline soils. We demonstrated a reduced contribution of microbial necromass to SOC and a shift in its composition towards the increase in bacterial origin in saline relative to non-saline soils. We concluded that salinity profoundly changes the biochemistry of SOC in arid regions.

The role of circRNAs and miRNAs in drug resistance and targeted therapy responses in breast cancer.

MicroRNAs (miRNAs) are small non-coding RNAs comprising 19-24 nucleotides that indirectly control gene expression. In contrast to other non-coding RNAs (ncRNAs), circular RNAs (circRNAs) are defined by their covalently closed loops, forming covalent bonds between the 3' and 5' ends. circRNAs regulate gene expression by interacting with miRNAs at transcriptional or post-transcriptional levels. Accordingly, circRNAs and miRNAs control many biological events related to cancer, including cell proliferation, metabolism, cell cycle, and apoptosis. Both circRNAs and miRNAs are involved in the pathogenesis of diseases, such as breast cancer. This review focuses on the latest discoveries on dysregulated circRNAs and miRNAs related to breast cancer, highlighting their potential as biomarkers for clinical diagnosis, prognosis, and chemotherapy response.

Implication of Amyloid Precursor-like Protein 2 Expression in Cutaneous Squamous Cell Carcinoma Pathogenesis.

BACKGROUND/AIM: Regulatory functions of amyloid precursor-like protein 2 (APLP2) expression in intracellular trafficking of major histocompatibility complex class I (MHC-I) and biological behavior of tumor cells have been reported in various types of malignancies but not in cutaneous squamous cell carcinoma (CSCC). This study aimed to investigate the role of APLP2 expression in the pathogenesis of CSCC. PATIENTS AND METHODS: The expression of APLP2 and a key modulator of cancer immune escape, MHC-I, were determined in CSCC tissue samples obtained from 141 patients using immunohistochemistry. The regulatory effects of APLP2 expression on the biological behavior and surface expression of MHC-I in CSCC cells were investigated by trypan blue assay, Matrigel invasion assay, and in vivo xenograft analysis. RESULTS: APLP2 immunoreactivity was high in 73 (51.8%) tissue samples from patients with CSCC and was significantly related to subcutaneous fat invasion and poor prognosis in our cohort. Moreover, proliferation of and invasion by CSCC cells were significantly reduced after APLP2 knockdown in CSCC cells both in vitro and in vivo. A significant association was found between APLP2 and membrane MHC-I expression in patients with CSCC. In vivo xenograft analysis showed that APLP2 knockdown increased membrane MHC-I expression in CSCC cells. CONCLUSION: APLP2 not only acts as an oncogene in CSCC progression but also as a possible modulator of cancer immune escape by influencing MHC-I expression on the cell surface. APLP2 may serve as a novel molecular biomarker and therapeutic target for patients with CSCC.

Deep-learning radiomics based on ultrasound can objectively evaluate thyroid nodules and assist in improving the diagnostic level of ultrasound physicians.

Background: The incidence rate of thyroid nodules has reached 65%, but only 5-15% of these modules are malignant. Therefore, accurately determining the benign and malignant nature of thyroid nodules can prevent unnecessary treatment. We aimed to develop a deep-learning (DL) radiomics model based on ultrasound (US), explore its diagnostic efficacy for benign and malignant thyroid nodules, and verify whether it improved the diagnostic level of physicians. Methods: We retrospectively included 1,076 thyroid nodules from 817 patients at three institutions. The radiomics and DL features of the US images were extracted and used to construct radiomics signature (Rad_sig) and deep-learning signature (DL_sig). A Pearson correlation analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were used for feature selection. Clinical US semantic signature (C_US_sig) was constructed based on clinical information and US semantic features. Next, a combined model was constructed based on the above three signatures in the form of a nomogram. The model was constructed using a development set (institution 1: 719 nodules), and the model was evaluated using two external validation sets (institution 2: 74 nodules, and institution 3: 283 nodules). The performance of the model was assessed using decision curve analysis (DCA) and calibration curves. Furthermore, the C_US_sigs of junior physicians, senior physicians, and expers were constructed. The DL radiomics model was used to assist the physicians with different levels of experience in the interpretation of thyroid nodules. Results: In the development and validation sets, the combined model showed the highest performance, with areas under the curve (AUCs) of 0.947, 0.917, and 0.929, respectively. The DCA results showed that the comprehensive nomogram had the best clinical utility. The calibration curves indicated good calibration for all models. The AUCs for distinguishing between benign and malignant thyroid nodules by junior physicians, senior physicians, and experts were 0.714-0.752, 0.740-0.824, and 0.891-0.908, respectively; however, with the assistance of DL radiomics, the AUCs reached 0.858-0.923, 0.888-0.944, and 0.912-0.919, respectively. Conclusions: The nomogram based on DL radiomics had high diagnostic efficacy for thyroid nodules, and DL radiomics could assist physicians with different levels of experience to improve their diagnostic level.

Granular bacterial inoculant alters the rhizosphere microbiome and soil aggregate fractionation to affect phosphorus fractions and maize growth.

The constraint of phosphorus (P) fixation on crop production in alkaline calcareous soils can be alleviated by applying bioinoculants. However, the impact of bacterial inoculants on this process remains inadequately understood. Here, a field study was conducted to investigate the effect of a high-concentration, cost-effective, and slow-release granular bacterial inoculant (GBI) on maize (Zea mays L.) plant growth. Additionally, we explored the effects of GBI on rhizosphere soil aggregate physicochemical properties, rhizosphere soil P fraction, and microbial communities within aggregates. The outcomes showed a considerable improvement in plant growth and P uptake upon application of the GBI. The application of GBI significantly enhanced the AP, phoD gene abundance, alkaline phosphatase activity, inorganic P fractions, and organic P fractions in large macroaggregates. Furthermore, GBI impacted soil aggregate fractionation, leading to substantial alterations in the composition of fungal and bacterial communities. Notably, key microbial taxa involved in P-cycling, such as Saccharimonadales and Mortierella, exhibited enrichment in the rhizosphere soil of plants treated with GBI. Overall, our study provides valuable insight into the impact of GBI application on microbial distributions and P fractions within aggregates of alkaline calcareous soils, crucial for fostering healthy root development and optimal crop growth potential. Subsequent research endeavors should delve into exploring the effects of diverse GBIs and specific aggregate types on P fraction and community composition across various soil profiles.

Photoswitchable dynamic conjugate addition-elimination reactions as a tool for light-mediated click and clip chemistry.

Phototriggered click and clip reactions can endow chemical processes with high spatiotemporal resolution and sustainability, but are challenging with a limited scope. Herein we report photoswitchable reversible covalent conjugate addition-elimination reactions toward light-addressed modular covalent connection and disconnection. By coupling between photochromic dithienylethene switch and Michael acceptors, the reactivity of Michael reactions was tuned through closed-ring and open-ring forms of dithienylethene, allowing switching on and off dynamic exchange of a wide scope of thiol and amine nucleophiles. The breaking of antiaromaticity in transition states and enol intermediates of addition-elimination reactions provides the driving force for photoinduced change in kinetic barriers. To showcase the versatile application, light-mediated modification of solid surfaces, regulation of amphiphilic assemblies, and creation/degradation of covalent polymers on demand were achieved. The manipulation of dynamic click/clip reactions with light should set the stage for future endeavors, including responsive assemblies, biological delivery, and intelligent materials.