Knockdown of KIF23 alleviates the progression of asthma by inhibiting pyroptosis.

BACKGROUND: Asthma is a chronic disease affecting the lower respiratory tract, which can lead to death in severe cases. The cause of asthma is not fully known, so exploring its potential mechanism is necessary for the targeted therapy of asthma. METHOD: Asthma mouse model was established with ovalbumin (OVA). H&E staining, immunohistochemistry and ELISA were used to detect the inflammatory response in asthma. Transcriptome sequencing was performed to screen differentially expressed genes (DEGs). The role of KIF23 silencing in cell viability, proliferation and apoptosis was explored by cell counting kit-8, EdU assay and flow cytometry. Effects of KIF23 knockdown on inflammation, oxidative stress and pyroptosis were detected by ELISA and western blot. After screening KIF23-related signalling pathways, the effect of KIF23 on p53 signalling pathway was explored by western blot. RESULTS: In the asthma model, the levels of caspase-3, IgG in serum and inflammatory factors (interleukin (IL)-1ß, KC and tumour necrosis factor (TNF)-α) in serum and bronchoalveolar lavage fluid were increased. Transcriptome sequencing showed that there were 352 DEGs in the asthma model, and 7 hub genes including KIF23 were identified. Knockdown of KIF23 increased cell proliferation and inhibited apoptosis, inflammation and pyroptosis of BEAS-2B cells induced by IL-13 in vitro. In vivo experiments verified that knockdown of KIF23 inhibited oxidative stress, inflammation and pyroptosis to alleviate OVA-induced asthma mice. In addition, p53 signalling pathway was suppressed by KIF23 knockdown. CONCLUSION: Knockdown of KIF23 alleviated the progression of asthma by suppressing pyroptosis and inhibited p53 signalling pathway.

The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients.

This meta-analysis aimed to evaluate the diagnostic accuracy of touch imprint cytology (TIC) for sentinel lymph node (SLN) metastases of patients with clinical node-negative early breast cancer. The PubMed, Web of Science, Embase, and the Cochrane Library databases were meticulously searched to retrieve literature published from January 2005 to September 2022 by two independent reviewers. The meta-analysis was performed using STATA16.0, Meta-Disc 1.4, and RevMan 5.4.9. According to the inclusion criteria, 4,073 patients from 13 studies were included in this meta-analysis. The pooled sensitivity and specificity of TIC for detecting SLN metastases were 0.77 (95% CI 0.66-0.85) and 0.99 (95% CI 0.97-1.00), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 76.15 (95% CI 29.16-198.84) and 0.23 (95% CI 0.15-0.36), respectively. The pooled diagnostic odds ratio was 326.82 (95% CI 132.76-804.56) and the area under the sROC curve was 0.97 (95% CI 0.95-0.98), respectively. This meta-analysis revealed that TIC with high sensitivity and specificity is a feasibility and accuracy diagnosis technique for intraoperative detection of SLN metastases in breast cancer.

Integrating the Soil Microbiota and Metabolome Reveals the Mechanism through Which Controlled Release Fertilizer Affects Sugarcane Growth.

Root-soil underground interactions mediated by soil microorganisms and metabolites are crucial for fertilizer utilization efficiency and crop growth regulation. This study employed a combined approach of soil microbial community profiling and non-targeted metabolomics to investigate the patterns of root-associated microbial aggregation and the mechanisms associated with metabolites under varying controlled-release fertilizer (CRF) application rates. The experimental treatments included five field application rates of CRF (D1: 675 kg/ha; D15: 1012.5 kg/ha; D2: 1350 kg/ha; D25: 1687.5 kg/ha; and D3: 2025 kg/ha) along with traditional fertilizer as a control (CK: 1687.5 kg/ha). The results indicated that the growth of sugarcane in the field was significantly influenced by the CRF application rate (p < 0.05). Compared with CK, the optimal field application of CRF was observed at D25, resulting in a 16.3% to 53.6% increase in sugarcane yield. Under the condition of reducing fertilizer application by 20%, D2 showed a 13.3% increase in stem yield and a 6.7% increase in sugar production. The bacterial ACE index exhibited significant differences between D25 and D1, while the Chao1 index showed significance among the D25, D1, and CK treatments. The dominant bacterial phyla in sugarcane rhizosphere aggregation included Proteobacteria, Actinobacteriota, and Acidobacteriota. Fungal phyla comprised Rozellomycota, Basidiomycota, and Ascomycota. The annotated metabolic pathways encompassed biosynthesis of secondary metabolites, carbohydrate metabolism, and lipid metabolism. Differential analysis and random forest selection identified distinctive biomarkers including Leotiomycetes, Cercospora, Anaeromyxobacter, isoleucyl-proline, and methylmalonic acid. Redundancy analysis unveiled soil pH, soil organic carbon, and available nitrogen as the primary drivers of microbial communities, while the metabolic profiles were notably influenced by the available potassium and phosphorus. The correlation heatmaps illustrated potential microbial-metabolite regulatory mechanisms under CRF application conditions. These findings underscore the significant potential of CRF in sugarcane field production, laying a theoretical foundation for sustainable development in the sugarcane industry.

Rhizosphere Fungal Dynamics in Sugarcane during Different Growth Stages.

Understanding the normal variation of the sugarcane rhizosphere fungal community throughout its life cycle is essential for the development of agricultural practices for fungal and ecological health associated with the microbiota. Therefore, we performed high-throughput sequencing of 18S rDNA of soil samples using the Illumina sequencing platform for correlation analysis of rhizosphere fungal community time series, covering information from 84 samples in four growth periods. The results revealed that the sugarcane rhizosphere fungi possessed the maximum fungal richness in Tillering. Rhizosphere fungi were closely associated with sugarcane growth, including Ascomycota, Basidiomycota, and Chytridiomycota, which showed high abundance in a stage-specific manner. Through the Manhattan plots, 10 fungal genera showed a decreasing trend throughout the sugarcane growth, and two fungal genera were significantly enriched at three stages of sugarcane growth (p < 0.05) including Pseudallescheria (Microascales, Microascaceae) and Nectriaceae (Hypocreales, Nectriaceae). In addition, soil pH, soil temperature, total nitrogen, and total potassium were critical drivers of fungal community structure at different stages of sugarcane growth. We also found that sugarcane disease status showed a significant and strong negative effect on selected soil properties by using structural equation modeling (SEM), suggesting that poor soil increases the likelihood of sugarcane disease. In addition, the assembly of sugarcane rhizosphere fungal community structure was mainly influenced by stochastic factors, but after the sugarcane root system became stable (Maturity), the stochastic contribution rate decreased to the lowest value. Our work provides a more extensive and solid basis for the biological control of sugarcane potential fungal diseases.

How to accurately preoperative screen nipple-sparing mastectomy candidate-a nomogram for predicting nipple-areola complex involvement risk in breast cancer patients.

BACKGROUND: Nipple-sparing mastectomy (NSM) offers superior cosmetic outcomes and has been gaining wide acceptance. It has always been difficult to objectively quantify the risk of nipple-areola complex involvement (NACi). The goal was to develop a prediction model for clinical application. METHODS: Patients who had a total mastectomy (TM) between January 2016 and January 2020 at a single institute formed the development cohort (n = 578) and those who had NSM + immediate breast reconstruction (IBR) between January 2020 and January 2021 formed the validation cohort (n = 112). The prediction model was developed using univariate and multivariate logistic regression studies. Based on NACi risk variables identified in the development cohort, a nomogram was created and evaluated in the validation cohort. Meanwhile, stratified analysis was performed based on the model's risk levels and was combined with intraoperative frozen pathology (IFP) to optimize the model. RESULTS: Tumor central location, clinical tumor size (CTS) > 4.0 cm, tumor-nipple distance (TND) ≤ 1.0 cm, clinical nodal status positive (cN +), and KI-67 ≥ 20% were revealed to be good predictive indicators for NACi. A nomogram based on these major clinicopathologic variables was employed to quantify preoperative NACi risk. The accuracy was verified internally and externally. The diagnostic accuracy of IFP was 92.9%, sensitivity was 64.3%, and specificity was 96.9% in the validation group. Stratified analysis was then performed based on model risk. The diagnostic accuracy rates of IFP and NACiPM in low-risk, intermediate-risk, and high-risk respectively were 96.0%, 93.3%, 83.9%, 61.3%, 66.7%, and 83.3%. CONCLUSION: We created a visual nomogram to predict NACi risk in breast cancer patients. The NACiPM can be used to distinguish the low, intermediate, and high risk of NAC before surgery. Combined with IFP, we can develop a decision-making system for the implementation of NSM.

Niche differentiation modulates metabolites abundance and composition in silicon fertilizer amended soil during sugarcane growth.

BACKGROUND: As one of the vital crops globally, sugarcane (Saccharum officinarum L.) has been one of model crops for conducting metabolome research. Although many studies have focused on understanding bioactive components in specific sugarcane tissues, crucial questions have been left unanswered about the response of metabolites to niche differentiation such as different sugarcane tissues (leaf, stem and root), and soil regions (rhizosphere and bulk) under silicon (Si) amended soils. Here, nontargeted metabolite profiling method was leveraged to assess the similarities and differences in the abundance and community composition of metabolites in the different sugarcane and soil compartments. Identify the compartment-specific expression patterns of metabolites, and their association with cane agronomic traits and edaphic factors. We also investigated the response of sugarcane agronomic traits and edaphic factors to Si amended soil. RESULTS: We found that Si fertilizer exhibited the advantages of overwhelmingly promoting the height and theoretical production of cane, and profoundly increased soil Si content by 24.8 and 27.0%, while soil available potassium (AK) was enhanced by 3.07 and 2.67 folds in the bulk and rhizosphere soils, respectively. It was also noticed that available phosphorus (AP) in the rhizosphere soil tremendously increased by 105.5%. We detected 339 metabolites in 30 samples using LC-MS/MS analyses, 161 of which were classified and annotated, including organooxygen compounds (19.9%), carboxylic acids and derivatives (15.5%), fatty acyls (15.5%), flavonoids (4.4%), phenols (4.4%), and benzene and substituted derivatives (3.7%). In addition, the total percentages covered by these core metabolites in each compartment ranged from 94.0% (bulk soil) to 93.4% (rhizosphere soil), followed by 87.4% (leaf), 81.0% (root) and 80.5% (stem), suggesting that these bioactive compounds may have migrated from the belowground tissues and gradually filtered in various aboveground niches of the plant. We also observed that the variations and enrichment of metabolites abundance and community were compartment-specific. Furthermore, some key bioactive compounds were markedly associated with plant growth parameters and soil edaphic. CONCLUSION: Taken together, we hypothesized that Si utilization can exhibit the advantage of enhancing edaphic factors and cane agronomic traits, and variations in metabolites community are tissue-specific.

Silicon fertilizer mediated structural variation and niche differentiation in the rhizosphere and endosphere bacterial microbiome and metabolites of sugarcane.

The microbiomes of plant are potential determinants of plant growth, productivity, and health. They provide plants with a plethora of functional capacities, namely, phytopathogens suppression, access to low-abundance nutrients, and resistance to environmental stressors. However, a comprehensive insight into the structural compositions of the bacterial abundance, diversity, richness, and function colonizing various microenvironments of plants, and specifically their association with bioactive compounds and soil edaphic factors under silicon (Si) amendment remains largely inconclusive. Here, high-throughput sequencing technology and nontargeted metabolite profiling method were adopted to test the hypotheses regarding microbiome niche abundance, diversity, richness, function, and their association with bioactive compounds and soil edaphic factors within different ecological niches (leaf, stem, root, rhizosphere, and bulk soils) under Si amendment during cane growth were we addressed. Our results demonstrated that Si correspondingly increased sugarcane theoretical production and yield, and remarkably enhanced soil nutrient status, especially Si, AP, and AK. It was also observed that bacterial diversity demonstrated tissue-dependent distribution patterns, with the bulk soil, rhizosphere soil, and root endosphere revealing the highest amount of bacterial diversity compared with the stem and leaf tissues. Moreover, Si exhibited the advantage of considerably promoting bacterial abundance in the various plant compartments. Co-occurrence interactions demonstrated that Si application has the potential to increase bacterial diversity maintenance, coexistence, and plant-soil systems bacteria connections, thereby increasing the functional diversity in the various plant tissues, which, in turn, could trigger positive growth effects in plants. Network analysis further revealed that metabolite profiles exhibited a strong association with bacterial community structures. It was also revealed that Si content had a considerable positive association with bacterial structures. Our findings suggest that the dynamic changes in microbe's community composition in different plant and soil compartments were compartment-specific. Our study provides comprehensive empirical evidence of the significance of Si in agriculture and illuminated on differential metabolite profiles and soil microbe's relationship.

Sugarcane Rhizosphere Bacteria Community Migration Correlates with Growth Stages and Soil Nutrient.

Plants and rhizosphere bacterial microbiota have intimate relationships. As neighbors of the plant root system, rhizosphere microorganisms have a crucial impact on plant growth and health. In this study, we sampled rhizosphere soil of sugarcane in May (seedling), July (tillering), September (elongation) and November (maturity), respectively. We employ 16S rRNA amplicon sequencing to investigate seasonal variations in rhizosphere bacteria community structure and abundance, as well as their association with soil edaphic factors. The results demonstrate that soil pH, total nitrogen (TN) and available nitrogen (AN) decrease substantially with time. Rhizosphere bacteria diversity (Shannon) and the total enriched OTUs are also significantly higher in July relative to other months. Bacteria OTUs and functional composition exhibit a strong and significant correlation with soil temperature (Tem), suggesting that Tem was the potential determinant controlling rhizosphere bacteria diversity, enriched OTUs as well as functional composition. Redundancy analysis (RDA) point toward soil total potassium (TK), pH, TN, Tem and AN as principal determinant altering shifting bacteria community structure. Variation partitioning analysis (VPA) analysis further validate that a substantial proportion of variation (70.79%) detected in the rhizosphere bacteria community structure was attributed to edaphic factors. Mfuzz analysis classified the bacterial genera into four distinct clusters, with cluster two exhibiting a distinct and dramatic increase in July, predominantly occupied by Allocatelliglobosispora. The stochastic forest model found the key characteristic bacterial populations that can distinguish the four key growth periods of sugarcane. It may help us to answer some pending questions about the interaction of rhizosphere microorganisms with plants in the future.

Integrated Metabolomics and Transcriptome Analyses Unveil Pathways Involved in Sugar Content and Rind Color of Two Sugarcane Varieties.

Metabolic composition can have potential impact on several vital agronomic traits, and metabolomics, which represents the bioactive compounds in plant tissues, is widely considered as a powerful approach for linking phenotype-genotype interactions. However, metabolites related to cane traits such as sugar content, rind color, and texture differences in different sugarcane cultivars using metabolome integrated with transcriptome remain largely inconclusive. In this study, metabolome integrated with transcriptome analyses were performed to identify and quantify metabolites composition, and have better insight into the molecular mechanisms underpinning the different cane traits, namely, brix, rind color, and textures in the stems (S) and leaves (L) of sugarcane varieties FN41 and 165402. We also identified metabolites and associated genes in the phenylpropanoid and flavonoid biosynthesis pathways, starch and sucrose metabolism. A total of 512 metabolites from 11 classes, with the vast majority (122) belonging to flavonoids were identified. Moreover, the relatively high amount of D-fructose 6-p, D-glucose6-p and glucose1-p detected in FN41L may have been transported and distributed by source and sink of the cane, and a majority of them reached the stem of sugarcane FN41L, thereby promoting the high accumulation of sugar in FN41S. Observations also revealed that genes such as C4H, CHS, F3H, F3'H, DFR, and FG2 in phenylpropanoid and flavonoid biosynthesis pathways were the major factors impacting the rind color and contrasting texture of FN41 and 165204. Further analysis revealed that weighted gene co-expression network analysis (WGCNA) hub genes and six transcription factors, namely, Tify and NAC, MYB-related, C2C2-Dof, WRKY, and bHLH play a key role in phenylpropanoid biosynthesis, flavone and flavonol biosynthesis, starch and sucrose metabolism. Additionally, metabolites such as L-phenylalanine, tyrosine, sinapaldehyde, pinobanksin, kaempferin, and nictoflorin were the potential drivers of phenotypic differences. Our finding also demonstrated that genes and metabolites in the starch and sucrose metabolism had a significant effect on cane sugar content. Overall, this study provided valuable insight into the molecular mechanisms underpinning high sugar accumulation and rind color in sugarcane, which we believe is important for future sugarcane breeding programs and the selection of high biomass varieties.

Multiple dsRNases Involved in Exogenous dsRNA Degradation of Fall Armyworm Spodoptera frugiperda.

RNAi is regarded as a promising technology for pest control. However, not all insects are sensitive to RNAi. Studies have confirmed that insect dsRNases are one of key factors affecting RNAi efficiency. In the current study, we identified four genes coding for dsRNases from the Spodoptera frugiperda genome. Spatial and temporal expression analysis showed that those dsRNases were highly expressed in the midgut and old larvae. Then a delivery method was applied for inducing efficient RNAi based on dsRNA encapsulated by liposome. Furthermore, we assessed degradation efficiency by incubation with dsRNA with gut juice or hemocoel to characterize potential roles of different SfdsRNases after suppression of SfdsRNase. The result showed that interferenced with any sfdsRNase reduced the degradation of exogenous dsRNA in midgut, interfered with sfdsRNase1 and sfdsRNase3 slowed down the degradation of exogenous dsRNA in hemolymph. Our data suggest the evolutionary expansion and multiple high activity dsRNase genes would take part in the RNAi obstinate in S. frugiperda, besides we also provide an efficient RNAi method for better use of RNAi in S. frugiperda.

CDK6-PI3K signaling axis is an efficient target for attenuating ABCB1/P-gp mediated multi-drug resistance (MDR) in cancer cells.

BACKGROUND: Multidrug resistance (MDR) mediated by ATP binding cassette subfamily B member 1 (ABCB1/P-gp) is a major cause of cancer chemotherapy failure, but the regulation mechanisms are largely unknown. METHODS: Based on single gene knockout, we studied the regulation of CDK6-PI3K axis on ABCB1-mediated MDR in human cancer cells. CRISPR/Cas9 technique was performed in KB-C2 cells to knockout cdk6 or cdk4 gene. Western blot, RT-PCR and transcriptome analysis were performed to investigate target gene deletion and expression of critical signaling factors. The effect of cdk4 or cdk6 deficiency on cell apoptosis and the cell cycle was analyzed using flow cytometry. In vivo studies were performed to study the sensitivity of KB-C2 tumors to doxorubicin, tumor growth and metastasis. RESULTS: Deficiency of cdk6 led to remarkable downregulation of ABCB1 expression and reversal of ABCB1-mediated MDR. Transcriptomic analysis revealed that CDK6 knockout regulated a series of signaling factors, among them, PI3K 110α and 110ß, KRAS and MAPK10 were downregulated, and FOS-promoting cell autophagy and CXCL1-regulating multiple factors were upregulated. Notably, PI3K 110α/110ß deficiency in-return downregulated CDK6 and the CDK6-PI3K axis synergizes in regulating ABCB1 expression, which strengthened the regulation of ABCB1 over single regulation by either CDK6 or PI3K 110α/110ß. High frequency of alternative splicing (AS) of premature ABCB1 mRNA induced by CDK6, CDK4 or PI3K 110α/110ß level change was confirmed to alter the ABCB1 level, among them 10 common skipped exon (SE) events were found. In vivo experiments demonstrated that loss of cdk6 remarkably increased the sensitivity of KB-C2 tumors to doxorubicin by increasing drug accumulation of the tumors, resulting in remarkable inhibition of tumor growth and metastasis, as well as KB-C2 survival in the nude mice. CONCLUSIONS: CDK6-PI3K as a new target signaling axis to reverse ABCB1-mediated MDR is reported for the first time in cancers. Pathways leading to inhibition of cancer cell proliferation were revealed to be accompanied by CDK6 deficiency.

Bio-fertilizer Affects Structural Dynamics, Function, and Network Patterns of the Sugarcane Rhizospheric Microbiota.

Fertilizers and microbial communities that determine fertilizer efficiency are key to sustainable agricultural development. Sugarcane is an important sugar cash crop in China, and using bio-fertilizers is important for the sustainable development of China's sugar industry. However, information on the effects of bio-fertilizers on sugarcane soil microbiota has rarely been studied. In this study, the effects of bio-fertilizer application on rhizosphere soil physicochemical indicators, microbial community composition, function, and network patterns of sugarcane were discussed using a high-throughput sequencing approach. The experimental design is as follows: CK: urea application (57 kg/ha), CF: compound fertilizer (450 kg/ha), BF1: bio-fertilizer (1500 kg/ha of bio-fertilizer + 57 kg/ha of urea), and BF2: bio-fertilizer (2250 kg/ha of bio-fertilizer + 57 kg/ha of urea). The results showed that the bio-fertilizer was effective in increasing sugarcane yield by 3-12% compared to the CF treatment group, while reducing soil acidification, changing the diversity of fungi and bacteria, and greatly altering the composition and structure of the inter-root microbial community. Variance partitioning canonical correspondence (VPA) analysis showed that soil physicochemical variables explained 80.09% and 73.31% of the variation in bacteria and fungi, respectively. Redundancy analysis and correlation heatmap showed that soil pH, total nitrogen, and available potassium were the main factors influencing bacterial community composition, while total soil phosphorus, available phosphorus, pH, and available nitrogen were the main drivers of fungal communities. Volcano plots showed that using bio-fertilizers contributed to the accumulation of more beneficial bacteria in the sugarcane rhizosphere level and the decline of pathogenic bacteria (e.g., Leifsonia), which may slow down or suppress the occurrence of diseases. Linear discriminant analysis (LDA) and effect size analysis (LEfSe) searched for biomarkers under different fertilizer treatments. Meanwhile, support vector machine (SVM) assessed the importance of the microbial genera contributing to the variability between fertilizers, of interest were the bacteria Anaerolineace, Vulgatibacter, and Paenibacillus and the fungi Cochliobolus, Sordariales, and Dothideomycetes between CF and BF2, compared to the other genera contributing to the variability. Network analysis (co-occurrence network) showed that the network structure of bio-fertilizers was closer to the network characteristics of healthy soils, indicating that bio-fertilizers can improve soil health to some extent, and therefore if bio-fertilizers can be used as an alternative to chemical fertilizers in the future alternative, it is important to achieve green soil development and improve the climate.

Impact of surgery on survival in breast cancer with bone metastases only: a SEER database retrospective analysis.

BACKGROUND: It was controversial to operate on the primary site of breast cancer (BC) with bone metastasis only. We investigated the impact of surgery on BC patients with bone metastases via a SEER database retrospective analysis. METHODS: A total of 2917 BC cases with bone metastasis, first diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and Results Database (SEER) of National Cancer Institute were selected. We assessed the effect of different surgical procedures on survival and prognosis. RESULTS: Compared with the non-surgical group, the primary tumor surgical group showed longer median survival time (χ2 = 146.023, P < 0.001), and the breast-conserving subgroup showed the highest median survival time of 70 months (χ2 = 157.117, P < 0.001). Compared with the non-surgery group, the median overall survival (OS) of primary surgery group was longer (HR = 0.525, 95%CI = 0.467-0.590, P < 0.001), and the breast-conserving subgroup showed the longest median operative OS (HR = 0.394, 95%CI = 0.325-0.478, P < 0.001). CONCLUSION: This study showed that primary surgery could improve the median survival time and OS of BC patients with bone metastasis. Moreover, under the condition of low tumor burden, breast conserving surgery was a better choice.

Continuous Sugarcane Planting Negatively Impacts Soil Microbial Community Structure, Soil Fertility, and Sugarcane Agronomic Parameters.

Continuous planting has a negative impact on sugarcane plant growth and reduces global sugarcane crop production, including in China. The response of soil bacteria, fungal, and arbuscular mycorrhizae (AM) fungal communities to continuous sugarcane cultivation has not been thoroughly documented. Using MiSeq sequencing technology, we analyzed soil samples from sugarcane fields with 1, 10, and 30 years of continuous cropping to see how monoculture time affected sugarcane yield, its rhizosphere soil characteristics and microbiota. The results showed that continuous sugarcane planting reduced sugarcane quality and yield. Continuous sugarcane planting for 30 years resulted in soil acidification, as well as C/N, alkali hydrolyzable nitrogen, organic matter, and total sulfur content significantly lower than in newly planted fields. Continuous sugarcane planting affected soil bacterial, fungal, and AM fungal communities, according to PCoA and ANOSIM analysis. Redundancy analysis (RDA) results showed that bacterial, fungal, and AM fungal community composition were strongly associated with soil properties and attributes, e.g., soil AN, OM, and TS were critical environmental factors in transforming the bacterial community. The LEfSe analysis revealed bacterial families (e.g., Gaiellaceae, Pseudomonadaceae, Micromonosporaceae, Nitrosomonadaceae, and Methyloligellaceae) were more prevalent in the newly planted field than in continuously cultivated fields (10 and 30 years), whereas Sphingomonadaceae, Coleofasciculaceae, and Oxyphotobacteria were depleted. Concerning fungal families, the newly planted field was more dominated than the continuously planted field (30 years) with Mrakiaceae and Ceratocystidaceae, whereas Piskurozymaceae, Trimorphomycetaceae, Lachnocladiaceae, and Stigmatodisc were significantly enriched in the continuously planted fields (10 and 30 years). Regarding AMF families, Diversisporaceae was considerably depleted in continuously planted fields (10 and 30 years) compared to the newly planted field. These changes in microbial composition may ultimately lead to a decrease in sugarcane yield and quality in the monoculture system, which provides a theoretical basis for the obstruction mechanism of the continuous sugarcane planting system. However, continuous planting obstacles remain uncertain and further need to be coupled with root exudates, soil metabolomics, proteomics, nematodes, and other exploratory methods.

Favorable Prognostic Impact of Cathepsin H (CTSH) High Expression in Thyroid Carcinoma.

BACKGROUND: Presently, no study reported the function of cathepsin H (CTSH) in thyroid carcinoma (THCA). The aim of present study was to initially explore the factors affecting CTSH expression, and association between CTSH expression and survival rate in THCA. METHODS: We explored mRNA expression of CTSH in normal and BRCA tissues, and evaluated prognostic impact of CTSH expression on the overall survival of THCA patients. Then, related factors influencing CTSH mRNA expression in THCA were analyzed. Functional enrichment analysis was performed to reveal the potential function of CTSH involved in THCA. We also constructed PPI network among co-expressed genes of CTSH to determine hub genes, followed by association analysis on hub genes with CTSH. RESULTS: (1) CTSH mRNA was highly expressed in THCA compared with normal group (P<0.001). High expression of CTSH was conducive to the overall survival of THCA patients (P=0.0027). CTSH was then determined as an independent prognostic factor in THCA (P=0.024). (2) The mRNA expression of CTSH was statistically related to patient's histological type, N stage, T stage, tumor stage and sample type (all P<0.001). CTSH copy number variation and methylation also influenced its mRNA expression (all P<0.001). (3) Pathway analysis indicated that CTSH mainly participated in cancer-related pathways, such as hedgehog signaling pathway, cytokine-cytokine receptor interaction and JAK-STAT signaling pathway (all P<0.05). (4) The top 10 co-expressed genes in whole PPI network showed significant correlation with CTSH expression (all P<0.001). CONCLUSION: CTSH higher expression was observed in THCA, which caused a good prognosis of patients. CTSH expression might be regulated by multiple factors including clinical characteristic, methylation, copy number and other genes. This study demonstrated the clinical significance of CTSH in THCA, as well as revealed the potential pathway associated with CTSH involved in thyroid cancer.

Soil Metagenomics Reveals Effects of Continuous Sugarcane Cropping on the Structure and Functional Pathway of Rhizospheric Microbial Community.

The continuous cropping of plants can result in the disruption of the soil microbial community and caused significant declines in yields. However, there are few reports on the effects of continuous cropping of sugarcane on the microbial community structure and functional pathway. In the current study, we analyzed the structural and functional changes of microbial community structure in the rhizospheric soil of sugarcane in different continuous cropping years using Illumina Miseq high-throughput sequencing and metagenomics analysis. We collected rhizosphere soils from fields of no continuous cropping history (NCC), 10 years of continuous cropping (CC10), and 30 years of continuous cropping (CC30) periods in the Fujian province. The results demonstrated that continuous sugarcane cropping resulted in significant changes in the physicochemical properties of soil and the composition of soil bacterial and fungal communities. With the continuous cropping, the crop yield dramatically declined from NCC to CC30. Besides, the redundancy analysis (RDA) of the dominant bacterial and fungal phyla and soil physicochemical properties revealed that the structures of the bacterial and fungal communities were mainly driven by pH and TS. Analysis of potential functional pathways during the continuous cropping suggests that different KEGG pathways were enriched in different continuous cropping periods. The significant reduction of bacteria associated with rhizospheric soil nitrogen and sulfur cycling functions and enrichment of pathogenic bacteria may be responsible for the reduction of effective nitrogen and total sulfur content in rhizospheric soil of continuous sugarcane as well as the reduction of sugarcane yield and sugar content. Additionally, genes related to nitrogen and sulfur cycling were identified in our study, and the decreased abundance of nitrogen translocation genes and AprAB and DsrAB in the dissimilatory sulfate reduction pathway could be the cause of declined biomass. The findings of this study may provide a theoretical basis for uncovering the mechanism of obstacles in continuous sugarcane cropping and provide better guidance for sustainable development of the sugarcane.

Diversity of microbial communities and soil nutrients in sugarcane rhizosphere soil under water soluble fertilizer.

The dynamics of soil microbial communities are important for plant health and productivity. Soil microbial communities respond differently to fertilization. Organic water soluble fertilizer is an effective soil improver, which can effectively improve soil nutrient status and adjust soil pH value. However, little is known about the effects of water soluble fertilizers on soil microbial community, and the combined effects on soil nutrients and sugarcane productivity. Therefore, this study sought to assess the effects of water soluble fertilizer (1,050 kg/hm2 (WS1), 1,650 kg/hm2 (WS2)) and mineral fertilizer (1,500 kg/hm2 (CK)) on the soil microbial community, soil nutrients and crop yield of sugarcane. The results showed that compared with CK, the application of water soluble fertilizers (WS1 and WS2) alleviated soil acidity, increased the OM, DOC, and AK contents in the soil, and further improved agronomic parameters and sugarcane yield. Both WS1 and WS2 treatments significantly increased the species richness of microorganisms, especially the enrichment of beneficial symbiotic bacteria such as Acidobacteria and Planctomycetes, which are more conducive to the healthy growth of plants. Furthermore, we found that soil nutrient contents were associated with soil microbial enrichment. These results indicate that water soluble fertilizer affects the enrichment of microorganisms by improving the nutrient content of the soil, thereby affecting the growth and yield of sugarcane. These findings therefore suggest that the utilization of water soluble fertilizer is an effective agriculture approach to improve soil fertility.

Sugarcane-Peanut Intercropping System Enhances Bacteria Abundance, Diversity, and Sugarcane Parameters in Rhizospheric and Bulk Soils.

Sugarcane-legume intercropping systems can effectively control pests and diseases as well as improve the fertility and health of farmland soil. However, little is known about the response of bacterial abundance, diversity, and community composition in the rhizosphere and non-rhizosphere soils under the sugarcane-peanut farming system. A field experiment was conducted with two treatments: sugarcane monoculture and sugarcane-peanut intercropping to examine the response of sugarcane parameters and edaphic factors. We also deciphered bacterial abundance, diversity, and community composition in the root endosphere, rhizosphere, and bulk soil by leveraging Illumina sequencing to conduct the molecular characterization of the 16S rRNA gene and nitrogenase (nifH) gene. We observed that sugarcane-peanut intercropping exhibited the advantages of tremendously increasing cane stalk height, stalk weight, and millable stalk number/20 m, and edaphic factors, namely, pH (1.13 and 1.93), and available phosphorus exhibited a fourfold and sixfold increase (4.66 and 6.56), particularly in the rhizosphere and bulk soils, respectively. Our result also showed that the sugarcane-peanut intercropping system significantly increased the bacterial richness of the 16S rRNA gene sequencing data by 13.80 and 9.28% in the bulk soil and rhizosphere soil relative to those in the monocropping sugarcane system, respectively. At the same time, sugarcane intercropping with peanuts significantly increased the Shannon diversity of nitrogen-fixing bacteria in the sugarcane rhizosphere soil. Moreover, most edaphic factors exhibited a positive regularity effect on bacterial community composition under the intercropping system. A linear discriminant analysis with effect size analysis of the 16S rRNA sequencing data revealed that bacteria in the root endosphere of the intercropped cane proliferated profoundly, primarily occupied by Devosia, Rhizobiales, Myxococcales, Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, Bradyrhizobium, and Sphingomonas. In conclusion, our findings demonstrated that sugarcane-peanut intercropping can enhance edaphic factors, sugarcane parameters, and bacterial abundance and diversity without causing adverse impacts on crop production and soil.

Metagenomic Analysis Exploring Taxonomic and Functional Diversity of Soil Microbial Communities in Sugarcane Fields Applied with Organic Fertilizer.

Organic fertilizers are critically important to soil fertility, microbial communities, and sustainable agricultural strategies. We compared the effect of two fertilizer groups (organic+chemical fertilizer: OM, chemical fertilizer: CK) on sugarcane growth, by observing the difference in microbial communities and functions, soil nutrient status, and agronomic characters of sugarcane. The results showed that the sugar content and yield of sugarcane increased significantly under organic fertilizer treatment. We believe that the increased soil nutrient status and soil microorganisms are the reasons for this phenomenon. In addition, redundancy analysis (RDA) shows that the soil nutrient condition has a major impact on the soil microbial community. In comparison with CK, the species richness of Acidobacteria, Proteobacteria, Chloroflexi, and Gemmatimonadetes as well as the functional abundance of nucleotide metabolism and energy metabolism increased significantly in the OM field. Moreover, compared with CK, genes related to the absorption and biosynthesis of sulfate were more prominent in OM. Therefore, consecutive organic fertilizer application could be an effective method in reference to sustainable production of sugarcane.

Recent progress in antitumor functions of the intracellular antibodies.

Conventional antibodies used for cancer therapies can only target the extracellular epitopes of tumor-associated antigens (TAAs); however, they struggle to enter cancer cells to interact with intracellular TAAs. Intrabodies are the engineered single-chain antibodies that can be transferred to the living cells or expressed within the cells and target the intracellular TAAs, owing to their nanosizes, enhanced motility and specific and potent binding affinities for the TAAs. Intrabody-based technology is a supplement to the current gene silencing technologies that can regulate a variety of biochemical processes and cellular functions and could be applicable for clinical treatment of tumors. Here, we review the development and current status of the intrabodies for the targeted treatment of cancers.