Adjacent Control Research Articles

Identification of DLL3-related genes affecting the prognosis of patients with colon adenocarcinoma.

Background: Delta-like ligand 3 (DLL3) is one of the NOTCH family of ligands, which plays a pro- or anti-carcinogenic role in some cancers. But the role of DLL3 in colon adenocarcinoma (COAD) has not been studied in depth. Materials and methods: First, we used Kaplan-Meier (K-M) curve to evaluate the effect of DLL3 on the prognosis of COAD in The Cancer Genome Atlas (TCGA), which was further validated in clinical samples for immunohistochemistry. Then we screened for differentially expressed genes (DEGs) of DLL3 by analyzing datasets of COAD samples from Gene Expression Omnibus (GEO) and TCGA. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and Gene Set Enrichment Analysis (GSEA) were conducted to explore the underlying mechanisms of DLL3-related in the development and prognosis of COAD. On the basis of DLL3-related signature genes, a prognostic model and a nomogram were constructed. Finally, CIBERSORT was applied to assess the proportion of immune cell types in COAD sample. Results: Survival analysis showed a significant difference in overall survival between high- and low-expression group (p = 0.0092), with COAD patients in the high-group having poorer 5-year survival rate. Gene functional enrichment analysis revealed that DLL3-related DEGs were mainly enriched in tumor- and immunity-related signaling pathways, containing AMPK pathway and mitophagy-animal. The comparison of COAD tumor and normal, DLL3 high- and low-expression groups by GSEA found that AMPK signaling pathway and mitophagy-animal were inhibited. Nomogram constructed from DLL3-related signature genes had a good predictive effect on the prognosis of COAD. We found the highest correlation between DLL3 and interstitial dendritic cell (iDC), natural killer (NK) cell and Interstitial dendritic cell (Tem). DLL3 was also revealed to be diagnostic for COAD. In clinical sample, we identified higher DLL3 expression in colon cancer tissue than in adjacent control (p < 0.0001) and in metastasis than in primary lesion (p = 0.0056). DLL3 expression was associated with stage and high DLL3 expression was observed to predict poorer overall survival (p = 0.004). Conclusion: It suggested that DLL3 may offer prognostic value and therapeutic potential for individualized treatment of COAD, and that it may has a diagnostic role in COAD.

Copper accumulation in five weed species commonly found in the understory vegetation of Mediterranean vineyards

Copper (Cu) concentration in agricultural soils often exceeds toxicological limits due to application of Cu-based fungicides. The potential of weeds for their use as functional cover plants in vineyard management and phytoremediation practices is little explored. We identified five weed species widely present in vineyards and assessed their Cu accumulation from eleven Mediterranean vineyards (soil Cu: 60–327 μg g−1) and two adjacent control sites (soil Cu: 15–30 μg g−1). Soils and plants were characterized by their physico-chemical properties and nutrient content. We applied multivariate techniques to analyze relationships between soil properties and leaf nutrient composition. Copper tolerance and accumulation traits were further tested in hydroponics using a series of CuSO4 concentrations (0.1–16 μM).Under field conditions, the highest Cu concentration in both roots and leaves were found in Lolium perenne (221 and 461 μg g−1, respectively), followed by Plantago lanceolata, Rumex obtusifolius and Taraxacum officinale (>100 μg g−1 Cu in leaves). Only one species, Trifolium repens, did not accumulate remarkable Cu concentrations. Overall, and as revealed by the multivariate analyses, leaf Cu concentration was driven by soil Cu content, soil texture, organic matter, nitrogen, and Cu uptake into roots. However, functional regression analysis and controlled experiments suggested that Cu might be additionally absorbed from the deposits on the leaf surface related to the Cu-fungicide treatments and soil dust. Our study highlights the importance of intra-specific variability in Cu accumulation among weed species in Cu-contaminated agricultural soils. Further validation of these findings under controlled conditions could provide essential insights for optimizing management and remediation strategies.

A hybrid trigger strategy based mixed impulsive control scheme on uncertain local field neural networks with leakage delay

Solved in this paper is the stabilization of uncertain local field neural networks (ULFNNs) with leakage delay by dint of a mixed impulsive control scheme. The impulsive control instants are decided by a Lyapunov functional-based event triggered scheme and a periodic impulse triggered scheme. Based on the proposed control scheme, sufficient conditions are deduced for eliminating the Zeno behavior and guaranteeing the uniform asymptotic stability (UAS) of the delayed ULFNNs in the framework of Lyapunov functional analysis method. Different from individual event triggered impulse control strategy where the triggered instants may be unexpected, the mixed impulsive control scheme can release the impulse control instants in line with the distance between any two adjacent successful control points, which improves the control performance and also achieves the goal of saving the communication resource. Furthermore, the decay behavior of impulse control signal is considered to make mathematical derivation more practical, and based on this behavior, a criterion is derived to make ensure the exponential stability of delayed ULFNNs. Finally, numerical examples are given to illustrate the effectiveness of the designed controller for the ULFNNs with leakage delay.

Spatial and temporal changes in biophysical skin parameters over a category I pressure ulcer.

In acute care facilities, the detection of pressure ulcers (PUs) relies on visual and manual examination of the patient's skin, which has been reported to be inconsistent and may lead to misdiagnosis. In skin and wound research, various biophysical parameters have been extensively employed to monitor changes in skin health. Nonetheless, the transition of these measures into care settings as part of a routine clinical assessment has been limited. This study was designed to examine the spatial and temporal changes in skin biophysical parameters over the site of a category I PU, in a cohort of hospitalised patients. Thirty patients, each presenting with a category I PU, were enrolled in the study. Skin integrity was assessed at the PU-compromised site and two adjacent areas (5 and 10 cm away). Data was collected over three sessions to examine both temporal differences and longitudinal changes. Skin integrity was assessed using two biophysical parameters, namely, transepidermal water loss (TEWL) and stratum corneum (SC) hydration. In addition, the influence of intrinsic factors, namely, incontinence and mobility status, on the parameters was evaluated. TEWL values at the sites compromised by PU were statistically significantly greater (P < .001) than corresponding values at the adjacent control sites at 5 and 10 cm, which were consistent with a normative range (<20 g/h/m2 ). By contrast, SC hydration values did not reveal clear distinctions between the three sites, with high inter-patient variation detected at the sites. Nevertheless, individual profiles were consistent across the three sessions, and the PU site was observed to be either abnormally dry or overhydrated in different individuals. No consistent temporal trend in either parameter was evident. However, intrinsic factors were shown to influence the parameters, with females, bedridden and incontinent patients presenting significantly higher TEWL and SC hydration values (P < .05). TEWL was able to identify differences in skin responses at skin sites compromised with a category I PU when compared to healthy adjacent skin sites. Accordingly, this parameter could be included in the clinical assessment for the identification of PU risk. Further studies are required to elucidate the role of hydration and skin barrier function in the development of PUs and their ability to monitor temporal changes in skin integrity.

Speed Adaptive Robot Trajectory Generation Based on Derivative Property of B-Spline Curve

In order to improve the safety of autonomous flight of quadrotor in three-dimensional complex environments, this paper proposes a speed adaptive motion planning method by limiting the distance between two adjacent control points based on the derivative property of B-Spline curve. First the initial B-Spline curve control points and the speed constraints based on derivative property are efficiently obtained by the front-end search that is divided into the shortest safe path search and reasonable step targeted expansion satisfying dynamic constraints. Then the back-end optimization assigns the corresponding safe flight corridor to the local trajectories according to the stage of the initial control points and uses MINVO basis ([1]) to limit the simplexes with minimum volume enclosing local trajectories. The trajectory generation is finally formulated as a Quadratically Constrained Quadratic Program (QCQP) which can be solved efficiently. Both simulations and real-world experiments validate the efficiency and performance of this method in generating safe, smooth, speed adaptive trajectories.

Identification of the key miRNA-mRNA regulatory network in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common type of lung cancer, has a high incidence rate and is a serious threat to human health. However, the pathogenesis of LUAD is still unclear. Further research on the pathogenesis of LUAD may provide targets for the early diagnosis and treatment of LUAD. First, a transcriptome analysis was conducted to sequence the messenger RNA (mRNA) and micro RNA (miRNA) of the LUAD and adjacent control tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were then performed for the functional annotation. Next, a differential miRNA-differential mRNA regulatory network was then constructed, and the function of the mRNAs in the network was analyzed and the key regulatory molecules (the hub molecules) were identified. Cytohubba was then used to analyze the top 20 hub molecules in the total miRNA-mRNA network, and the miRNAs regulating the top 20 hub genes (of which 2 were upregulated and 18 were downregulated). Finally, the key molecules were identified. By analyzing the function of the mRNA molecules in the regulatory network, we found that the immune response was inhibited, as were the movement and adhesion of immune-related cells; however, cell tumorigenesis, body death, and tumor cell proliferation were activated. The functions of the 20 hub molecules were mainly related to cytotoxicity, cell exosmosis, and cell adhesion mediated by immune cells. Further, we found that miR-5698, miR224-5p, and miR4709-3P regulate multiple key genes (e.g., PECAM1, CX3CR1, KLRD1, and CXCL12), and may be the key miRNAs regulating LUAD. Immune response, cell tumorigenesis, and tumor cell proliferation play central roles in the overall regulatory network. miR-5698, miR224-5p, and miR4709-3p may be important biomarkers for the occurrence and development of LUAD and have great potential in the prognosis of LUAD patients and the development of new therapeutic targets.

Long-term exclusion of invasive ungulates alters tree recruitment and functional traits but not total forest carbon.

Forests are major carbon (C) sinks, but their ability to sequester C and thus mitigate climate change, varies with the environment, disturbance regime, and biotic interactions. Herbivory by invasive, nonnative ungulates can have profound ecosystem effects, yet its consequences for forest C stocks remain poorly understood. We determined the impact of invasive ungulates on C pools, both above- and belowground (to 30 cm), and on forest structure and diversity using 26 paired long-term (>20 years) ungulate exclosures and adjacent unfenced control plots located in native temperate rainforests across New Zealand, spanning 36-41° S. Total ecosystem C was similar between ungulate exclosure (299.93 ± 25.94 Mg C ha-1 ) and unfenced control (324.60 ± 38.39 Mg C ha-1 ) plots. Most (60%) variation in total ecosystem C was explained by the biomass of the largest tree (mean diameter at breast height [dbh]: 88 cm) within each plot. Ungulate exclusion increased the abundance and diversity of saplings and small trees (dbh ≥2.5, <10 cm) compared with unfenced controls, but these accounted for ~5% of total ecosystem C, demonstrating that a few, large trees dominate the total forest ecosystem C but are unaffected by invasive ungulates at a timescale of 20-50 years. However, changes in understory C pools, species composition, and functional diversity did occur following long-term ungulate exclusion. Our findings suggest that, although the removal of invasive herbivores may not affect total forest C at the decadal scale, major shifts in the diversity and composition of regenerating species will have longer term consequences for ecosystem processes and forest C.

Climate change-related warming reduces thermal sensitivity and modifies metabolic activity of coastal benthic bacterial communities

Besides long-term average temperature increases, climate change is projected to result in a higher frequency of marine heatwaves. Coastal zones are some of the most productive and vulnerable ecosystems, with many stretches already under anthropogenic pressure. Microorganisms in coastal areas are central to marine energy and nutrient cycling and therefore, it is important to understand how climate change will alter these ecosystems. Using a long-term heated bay (warmed for 50 years) in comparison with an unaffected adjacent control bay and an experimental short-term thermal (9 days at 6–35 °C) incubation experiment, this study provides new insights into how coastal benthic water and surface sediment bacterial communities respond to temperature change. Benthic bacterial communities in the two bays reacted differently to temperature increases with productivity in the heated bay having a broader thermal tolerance compared with that in the control bay. Furthermore, the transcriptional analysis showed that the heated bay benthic bacteria had higher transcript numbers related to energy metabolism and stress compared to the control bay, while short-term elevated temperatures in the control bay incubation experiment induced a transcript response resembling that observed in the heated bay field conditions. In contrast, a reciprocal response was not observed for the heated bay community RNA transcripts exposed to lower temperatures indicating a potential tipping point in community response may have been reached. In summary, long-term warming modulates the performance, productivity, and resilience of bacterial communities in response to warming.

Optimal switching sequence control for current stress reduction of DC-link capacitors in dual-three phase PMSM drives

The safety and installation space of DC-link capacitor is crucial for dual-three phase permanent magnet synchronous machines (DTPMSM) drives in industrial applications. Reducing the capacitor current stress can contribute to decrease the designed capacitor value and install size, thus enhance safety of drives fed by two parallel inverters. Therefore, an optimal switching sequence control scheme for DTPMSM drives is proposed to reduce the DC-link capacitor current stress in this paper. For DTPMSM drives, the maximum four adjacent voltage vectors control (MFAVC) method is usually adopted due to its control flexible and stability characteristic. Based on MFAVC, the capacitor current can be derived though the current reconstruction theory to reorder the current amplitude over one switching period. Through the rearrangement of voltage vector and duration, the theoretical analysis of capacitor current reduction is presented. On this basis, the optimal switching sequence control method can be implemented based on the minimized current sum of the two inverters. The performance of proposed method has been evaluated via. comparatively experimental tests on a prototype 3 kW DTPMSM drive, which shows superior features on reducing capacitor current stress. Furthermore, it is also found that the proposed method is helpful to redesign a small capacitor value for DTPMSM drives.

Inflammatory biomarkers in sebum for identifying skin damage in patients with a Stage I pressure ulcer in the pelvic region: A single centre observational, longitudinal cohort study with elderly patients.

Pressure Ulcers (PU) are a major burden for affected patients and healthcare providers. Current detection methods involve visual assessments of the skin by healthcare professionals. This has been shown to be subjective and unreliable, with challenges associated with identifying erythema in darker colour skin. Although there exists a number of promising non-invasive biophysical techniques such as ultrasound, capacitance measurements, and thermography, the present study focuses on directly measuring the changes in the inflammatory status of the skin and underlying tissues. Therefore, in this study, we aim to analyse inflammatory cytokines collected through non-invasive sampling techniques to detect early signs of skin damage. Thirty hospitalised patients presenting with Stage I PU were recruited to evaluate the inflammatory response of skin at the site of damage and an adjacent healthy control site. Sebutapes were collected over three sessions to investigate the temporal changes in the inflammatory response. The panel of cytokines investigated included high-abundance cytokines, namely, IL-1α and IL-1RA, and low abundance cytokines; IL-6, IL-8, TNF-α, INF-γ, IL-33, IL-1β and G-CSF. Spatial and temporal differences between sites were assessed and thresholds were used to determine the sensitivity and specificity of each biomarker. Theresultssuggest significant (P < .05) spatial changes in the inflammatory response, with upregulation of IL-1α, IL-8, and G-CSF as well as down-regulation of IL-1RA over the Stage I PU compared with the adjacent control site. There were no significant temporal differences between the three sessions. Selected cytokines, namely, IL-1α, IL-1RA, IL-8, G-CSF, and the ratio IL-1α/IL-1RA offered clear delineation in the classification of healthy and Stage-I PU skin sites, with receiver operating characteristic curves demonstrating high sensitivity and specificity. There were limited influences of intrinsic and extrinsic factors on the biomarker response. Inflammatory markers provided a high level of discrimination between the sites presenting with Stage I PU and an adjacent healthy skin site, in a cohort of elderly inpatients. Indeed, the ratio of IL-1α to IL-1RA provided the highest sensitivity and specificity, indicative that inflammatory homeostasis is affected at the PU site. There was a marginal influence of intrinsic and extrinsic factors, demonstrating the localised effects of the inflammation. Further studies are required to investigate the potential of inflammatory cytokines incorporated within Point of Care technologies, to support routine clinical use.

Multimode Model Predictive Control for PMSM Drive System

In order to improve the control performance of the motor model predictive control (MPC) system, a multimode hybrid-vector MPC strategy is proposed in this article, which is developed from the conventional double-vector MPC strategy. The proposed method extends the last voltage vector of the previous control period to the present control period according to the relationship between the last voltage vector of the previous control period and the first voltage vector of the present control period. Then, two voltage vectors or three voltage vectors are included in each control period, which forms the concept of the hybrid vector. Since a voltage vector is inherited from the previous control period, the proposed method can achieve better steady-state control performance at a lower switching frequency, considering the two adjacent control periods as a whole. Finally, comparative experiments demonstrate that the proposed method has better steady-state control performance at the same switching frequency.

Dysregulated cholesterol regulatory genes as a diagnostic biomarker for cancer.

A dysregulation of cholesterol homeostasis is often seen in various cancer cell types, and elevated cholesterol content and that of its metabolites appears to be crucial for cancer progression and metastasis. Cholesterol is a precursor of various steroid hormones and a key plasma membrane component especially in lipid-rafts, also modulating many intracellular signaling pathways. To provide an insight of dysregulated cholesterol regulatory genes, their transcript levels were analyzed in different cancers and their influence was correlated with the overall survival of cancer patients using cancer database analysis. This analysis found a set of genes (e.g., ACAT1, RXRA, SOAT1 and SQLE) that were not only often dysregulated, but also had been associated with poorer overall survival in most cancer types. Quantitative reverse transcriptase-polymerase chain reaction analysis revealed elevated SQLE and SOAT1 transcript levels and downregulated expression of RXRA and ACAT1 genes in triple negative breast cancer tissues compared to adjacent control tissues, indicating that this dysregulated expression of the gene signature is a diagnostic marker for breast cancer. For the first time, the present study identified a gene signature associated with the dysregulation of cholesterol homeostasis in cancer cells that may not only be used as a diagnostic marker, but also comprise a promising drug target for the advancement of cancer therapy.

The Co-Expression of Estrogen Receptors ERα, ERβ, and GPER in Endometrial Cancer.

Estrogens have important roles in endometrial cancer (EC) and exert biological effects through the classical estrogen receptors (ERs) ERα and ERβ, and the G-protein-coupled ER, GPER. So far, the co-expression of these three types of ERs has not been studied in EC. We investigated ERα, ERβ, GPER mRNA and protein levels, and their intracellular protein distributions in EC tissue and in adjacent control endometrial tissue. Compared to control endometrial tissue, immunoreactivity for ERα in EC tissue was weaker for nuclei with minor, but unchanged, cytoplasmic staining; mRNA and protein levels showed decreased patterns for ERα in EC tissue. For ERβ, across both tissue types, the immunoreactivity was unchanged for nuclei and cytoplasm, although EC tissues again showed lower mRNA and protein levels compared to adjacent control endometrial tissue. The immunoreactivity of GPER as well as mRNA levels of GPER were unchanged across cancer and control endometrial tissues, while protein levels were lower in EC tissue. Statistically significant correlations of estrogen receptor α (ESR1) versus estrogen receptor β (ESR2) and GPER variant 3,4 versus ESR1 and ESR2 was seen at the mRNA level. At the protein level studied with Western blotting, there was significant correlation of ERα versus GPER, and ERβ versus GPER. While in clinical practice the expression of ERα is routinely tested in EC tissue, ERβ and GPER need to be further studied to examine their potential as prognostic markers, provided that specific and validated antibodies are available.

Using Fish Assemblages to Assess the Ecological Effects of Marine Protection on Rocky Habitats in a Portuguese Natural Park

Intensive and regular fishing occurs in the marine area of the natural park “Parque Natural do Sudoeste Alentejano e Costa Vicentina” (PNSACV; SW coast of continental Portugal). In 2011, this area became a marine park with different protection levels (total, partial, and complementary). We assessed in 2011 and 2012 if partial protection (PP) in Marine Protected Areas (MPAs) changed the taxa richness, abundance, size, and community composition of cryptic and non-cryptic fishes. We also determined if these effects were observed outside PP areas in adjacent control areas. Underwater visual censuses (UVC) of cryptic and non-cryptic fish species were conducted in rocky subtidal habitats (~10 m deep) with band transects (25 × 2 m and 25 × 4 m, respectively) to determine abundance and size classes. The northern half of the PNSACV was sampled at a scale of tens (site—two sites per area; 4–6 transects per site) and hundreds (area) of meters. Two PP and six control areas were sampled. The homogeneity and abundance of bottom habitat types were assessed at each site. Effects of protection were not detected in the community structure or univariate analyses (i.e., taxa richness and total abundance) of non-cryptic and cryptic fishes. The early phase of the MPAs may have driven the lack of significant protection effects. Replication in time within a monitoring program is recommended to assess these conservation measures’ ecological effects.

Chromatin-Accessible miRNA Regulons Driving Thyroid Tumorigenesis and Progression.

Although papillary thyroid cancer can remain indolent, associated lymph node metastases and recurrence rates are approximately 50% and 20%, respectively. Omics-based medicine has led to the discovery of predictive biomarkers that can be used to predict tumor progression and clinical outcomes. We aimed to develop a noninvasive omics-driven blood test to allow accurate risk stratification and help tailor individual patient treatment plans. RNA sequencing (seq) and microRNA analysis of The Cancer Genome Atlas and Gene Expression Omnibus datasets were employed to identify an epigenetic prognostic panel. Integrated bulk assay for transposase-accessible chromatin-seq and RNA-seq experiments confirmed the results. Sixty-two paired tumor and adjacent control thyroid tissues and 67 blood samples (62 papillary thyroid cancer and 5 controls) were analyzed for validation using sequencing and real-time polymerase chain reaction and correlated to clinical outcomes. A liposome-exosome fusion clustered regularly interspaced short palindromic repeats (CRISPR)-fluorescent detection system miRNA assay was developed. A predictive risk nomogram was generated and tested for performance. Our miRNA panel (miR-146b-5p and miR-221-3p) from tissue and blood was associated with aggressive features and was located within accessible chromatin regions. The miRNA risk score and prognostic nomogram showed higher accuracy in predicting lymph node metastases (miR-146b: area under the curve [AUC] 0.816, sensitivity 76.9%; miR-221: AUC 0.740, sensitivity 79.5%) and recurrence (miR-146b: AUC 0.921, sensitivity 75.0%; miR-221: AUC 0.756, sensitivity 70.0%; p < 0.001) than staging and American Thyroid Association risk stratification. CRISPR-based miRNA assays showed upregulation in the blood of cancer cohorts. CRISPR-based detection of miR-146b and miR-221 in the blood of thyroid cancer patients is a reliable and noninvasive tool for real-time assessment and prognostication that has great potential to provide a direct impact on the care of these patients.

Raccoon abundance indexing and removal: implications for Blanding’s turtle nest success

Context Elevated mesopredator populations can pose a threat to species of conservation concern. Aims We sought to evaluate the effectiveness of raccoon removal on their abundance and on Blanding’s turtle nest success. Methods We used an index of raccoon abundance generated from camera-trap data and information on the success of Blanding’s turtle nests to compare adjacent control and raccoon-removal sites. Key results Raccoon detections were more frequent and abundance index values were higher at control sites than at the removal site. However, Blanding’s turtle nest success did not differ between control and removal sites, likely because of differences in nest location and camera proximity. Conclusions The efficacy of raccoon removal for Blanding’s turtle conservation may vary with nest habitat characteristics and can benefit from a priori knowledge of nesting areas. Implications Mesopredator removal can be beneficial to species of conservation concern, provided it occurs in areas of greatest impact.

Do regenerative grazing management practices improve vegetation and soil health in grazed rangelands? Preliminary insights from a space-for-time study in the Great Barrier Reef catchments, Australia

Regenerative grazing, which generally involves some form of rotational grazing with strategic rest, is increasingly seen as a profitable management approach that will accelerate landscape recovery. However, there is limited quantitative evidence supporting the benefits of this approach in northern Australia. This space-for-time study collected vegetation and soil data from a range of properties in the Burdekin catchment in Queensland that have implemented regenerative grazing strategies for between 5 and 20 years. Data were also collected at adjacent control sites that did not undergo regenerative grazing, but where more traditional continuous set-stocking grazing approaches were applied. Coincident data were also collected from several sites where grazing had been excluded for ~30 years. Data suggested that improvements in vegetation, soil and land condition can be obtained from implementing regenerative grazing principles, although it is likely to take at least 3–5 years, and up to 15–20 years for statistically significant improvements to be measurable at a site, particularly for areas that are moving from a degraded baseline condition. Vegetation attributes such as plant biomass and basal area and litter incorporation all appeared to be better surrogates than percentage ground cover for representing improved landscape condition and soil health. Sites that maintained remotely sensed percentage ground cover at or above the minimally disturbed reference benchmark levels for &gt;10 years, as well as having statistically higher biomass, basal area and litter, had significant increases in total nitrogen (TN) and soil organic carbon (SOC) relative to the local control site. Although there are indications that regenerative grazing can lead to improvements in land condition, this study does not enable us to conclude whether regenerative grazing will accelerate improvements compared with other best-practice grazing land management (GLM) approaches, and further research on the social and economic dimensions of regenerative grazing is needed.

M6A regulators featured by tumor immune microenvironment landscapes and correlated with immunotherapy in non-small cell lung cancer (NSCLC).

Recent research has confirmed the critical role that epigenetic factors play in regulating the immune response. Nonetheless, what role m6A methylation modification might play in the immune response of non-small cell lung cancer (NSCLC) remains vague. Herein, the gene expression, copy number variations (CNVs), and somatic mutations of 31 m6A regulators in NSCLC and adjacent control samples from the GEO and TCGA databases were comprehensively explored. Using consensus clustering, m6A modification patterns were identified. Correlations between m6A modification patterns and immune cell infiltration traits in the tumor immune microenvironment (TME) were systematically analyzed. Differentially expressed genes were verified and screened by random forest and cox regression analysis by comparing different m6A modification patterns. Based on the retained gene panel, a risk model was built, and m6Ascore for each sample was calculated. The function of m6Ascore in NSCLC prognosis, tumor somatic mutations, and chemotherapy/immunotherapy response prediction were evaluated. Consensus clustering classified all NSCLC samples into two m6A clusters (m6A_clusterA and m6A_clusterB) according to the expression levels of 25 m6A regulator genes. Hierarchical clustering further divides the NSCLC samples into two m6A gene clusters: m6AgeneclusterA and m6AgeneclusterB. A panel of 83 genes was screened from the 194 differentially expressed genes between m6A gene clusters. Based on this, a risk score model was established. m6A modification clusters, m6A gene clusters, and m6Ascore calculated from the risk model were able to predict tumor stages, immune cell infiltration, clinical prognosis, and tumor somatic mutations. NSCLC patients with high m6Ascore have poor drug resistance to chemotherapy drugs (Cisplatin and Gemcitabine) and exhibit considerable therapeutic benefits and favorable clinical responses to anti-PD1 or anti-CTLA4 immunotherapy. In conclusion, methylation modification patterns mediated by the m6A regulators in individuals play a non-negligible role in prognosis prediction and immunotherapy response, which will facilitate personalized treatment and immunotherapeutic strategies for NSCLC patients in the future.

Correlated downregulation of VDR and CYP3A4 in colorectal cancer.

The evidence obtained from experimental studies suggests the tumor-suppressive effects of vitamin D by controlling the differentiation, proliferation, and apoptosis in cancerous cells. Furthermore, the deregulation of genes involved in vitamin D metabolism has been reported in several types of cancer. In the present study, we investigated the expression level of vitamin D metabolic pathway genes, including VDR, CYP3A4, RXRα, and GC, in colorectal cancer (CRC) samples compared with the adjacent tissues by using quantitative RT-PCR. The results indicated significant downregulation of CYP3A4 and VDR genes in CRC tissues compared with the adjacent control tissues (p < 0.01). RXRA and GC expression levels did not show any significant alteration among the studied samples. Moreover, a positive correlation was observed between the expression level of CYP3A4 and VDR genes (p < 0.0001). ROC curve analysis also revealed the potential diagnostic power of CYP3A4 and VDR genes in CRC samples. Reduction in the expression of both CYP3A4 and VDR plays an important role in CRC due to the possible impairment in vitamin D metabolism. Further studies concerning the relationship between the expression of these genes and colorectal cancer pathogenesis and treatment are recommended.

Research on Three Cylinder Synchronous Control Based on Tracking Differentiator and Fuzzy PID

Aiming at the problem of three-cylinder asynchronous caused by nonlinear factors in the three-cylinder synchronous control system, a fuzzy PID synchronous control method with a tracking differentiator based on an adjacent cross-coupling control strategy is proposed. Fuzzy PID control is used to adjust P, I, and D parameters online, and the tracking differentiator is used in fuzzy control to filter the input error and error differential of fuzzy control. After the controller design is completed, the combined simulation model of the three-cylinder control system is built by AMESim and Simulink. The simulation results verify that the performance of the fuzzy PID controller with tracking differentiator is smaller than the maximum synchronization and average error of the ordinary PID, which can be better applied to the three-cylinder synchronous control system.