Effect of ultrasound-guided stellate ganglion block on inflammatory cytokines and postoperative recovery after partial hepatectomy: a randomised clinical trial.

BACKGROUND: Stellate ganglion block (SGB) has been shown to reduce perioperative complications in various surgeries. Because laparoscopic techniques and instruments have advanced during the past two decades, laparoscopic liver resection is being increasingly adopted worldwide. Lesser blood loss, fewer postoperative complications, and shorter postoperative hospital stays are the advantages of laparoscopic liver resection, as compared to conventional open surgery. There is an urgent need for an effective intervention to reduce perioperative complications and accelerate postoperative recovery. This study investigated the effect of ultrasound-guided SGB on enhanced recovery after laparoscopic partial hepatectomy. METHODS: We compared patients who received SGB with 0.5% ropivacaine (group S) with those who received SGB with 0.9% saline (group N). A total of 58 patients with partial hepatectomy were enrolled (30 S) and (28 N). Before induction of anesthesia, SGB was performed with 0.5% ropivacaine in group S and 0.9% saline in group N. MAIN OUTCOME: Comparison of serum inflammatory cytokines concentration at each time point. RESULTS: Main outcome: When comparing IL-6 and IL-10 concentrations among groups, group S showed less variation over time compared to group N. For comparison between groups, the serum IL-6 concentration in group S was lower than that in group N at 6 and 24 h after operation (P < 0.01), and there was a significant linear relationship between serum IL-6 concentration at 24 h after operation and hospitalization situation. CONCLUSIONS: Ultrasound-guided SGB can stabilize perioperative inflammatory cytokines plays a positive role in the enhanced recovery of patients after laparoscopic partial hepatectomy. The serum IL-6 level within 24 h after surgery may be used as a predictor of hospitalization. TRIAL REGISTRATION: The study was registered at the ClinicalTrials.gov (Registration date: 13/09/2021; Trial ID: NCT05042583).

Molecular evolution and interaction of 14-3-3 proteins with H+-ATPases in plant abiotic stresses.

Environmental stresses severely affect plant growth and crop productivity. Regulated by 14-3-3 proteins (14-3-3s), H+-ATPases (AHAs) are important proton pumps that can induce diverse secondary transport via channels and co-transporters for the abiotic stress response of plants. Many studies demonstrated the roles of 14-3-3s and AHAs in coordinating the processes of plant growth, phytohormone signaling, and stress responses. However, the molecular evolution of 14-3-3s and AHAs has not been summarized in parallel with evolutionary insights across multiple plant species. Here, we comprehensively review the roles of 14-3-3s and AHAs in cell signaling to enhance plant responses to diverse environmental stresses. We analyzed the molecular evolution of key proteins and functional domains that are associated with 14-3-3s and AHAs in plant growth and hormone signaling. The results revealed evolution, duplication, contraction, and expansion of 14-3-3s and AHAs in green plants. We also discussed the stress-specific expression of those 14-3-3and AHA genes in a eudicotyledon (Arabidopsis thaliana), a monocotyledon (Hordeum vulgare), and a moss (Physcomitrium patens) under abiotic stresses. We propose that 14-3-3s and AHAs respond to abiotic stresses through many important targets and signaling components of phytohormones, which could be promising to improve plant tolerance to single or multiple environmental stresses.

Allene oxide synthase 1 contributes to limiting grain arsenic accumulation and seedling detoxification in rice.

Arsenic (As) is a cancerogenic metalloid ubiquitously distributed in the environment, which can be easily accumulated in food crops like rice. Jasmonic acid (JA) and its derivatives play critical roles in plant growth and stress response. However, the role of endogenous JA in As accumulation and detoxification is still poorly understood. In this study, we found that JA biosynthesis enzymes Allene Oxide Synthases, OsAOS1 and OsAOS2, regulate As accumulation and As tolerance in rice. Evolutionary bioinformatic analysis indicated that AOS1 and AOS2 have evolved from streptophyte algae (e.g. the basal lineage Klebsormidium flaccidum) - sister clade of land plants. Compared to other two AOSs, OsAOS1 and OsAOS2 were highly expressed in all examined rice tissues and their transcripts were highly induced by As in root and shoot. Loss-of-function of OsAOS1 (osaos1-1) showed elevated As concentration in grains, which was likely attributed to the increased As translocation from root to shoot when the plants were subjected to arsenate [As(V)] but not arsenite [As (III)]. However, the mutation of OsAOS2 (osaos2-1) showed no such effect. Moreover, osaos1-1 and osaos2-1 increased the sensitivity of rice plants to both As(V) and As(III). Disrupted expression of genes involved in As accumulation and detoxification, such as OsPT4, OsNIP3;2, and OsOASTL-A1, was observed in both osaos1-1 and osaos2-1 mutant lines. In addition, a As(V)-induced significant decrease in Reactive Oxygen Species (ROS) production was observed in the root of osaos1-1 but not in osaos2-1. Taken together, our results indicate OsAOS1 modulates both As allocation and detoxification, which could be partially attributed to the altered gene expression profiling and ROS homeostasis in rice while OsAOS2 is important for As tolerance.

Integrated physiological and omics analyses reveal the mechanism of beneficial fungal Trichoderma sp. alleviating cadmium toxicity in tobacco (Nicotiana tabacum L.).

Cadmium (Cd) is a highly toxic heavy metal and readily accumulates in tobacco, which imperils public health via Cd exposure from smoking. Beneficial microbes have a pivotal role in promoting plant growth, especially under environmental stresses such as heavy metal stresses. In this study, we introduced a novel fungal strain Trichoderma nigricans T32781, and investigated its capacity to alleviate Cd-induced stress in tobacco plants through comprehensive physiological and omics analyses. Our findings revealed that T32781 inoculation in soil leads to a substantial reduction in Cd-induced growth inhibition. This was evidenced by increased plant height, enhanced biomass accumulation, and improved photosynthesis, as indicated by higher values of key photosynthetic parameters, including the maximum quantum yield of photosystem Ⅱ (Fv/Fm), stomatal conductance (Gs), photosynthetic rate (Pn) and transpiration rate (Tr). Furthermore, element analysis demonstrated that T. nigricans T32781 inoculation resulted in a remarkable reduction of Cd uptake by 62.2% and a 37.8% decrease in available soil Cd compared to Cd-stressed plants without inoculation. The protective role of T32781 extended to mitigating Cd-induced oxidative stress by improving antioxidant enzyme activities of superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX). Metabolic profiling of tobacco roots identified 43 key metabolites, with notable contributions from compounds like nicotinic acid, succinic acid, and fumaric acid in reducing Cd toxicity in T32781-inoculated plants. Additionally, rhizosphere microbiome analysis highlighted the promotion of beneficial microbes, including Gemmatimonas and Sphingomonas, by T32781 inoculation, which potentially contributed to the restoration of plant growth under Cd exposure. In summary, our study demonstrated that T. nigricans T32781 effectively alleviated Cd stress in tobacco plants by reducing Cd uptake, alleviating Cd-induced oxidative stress, influencing plant metabolite and modulating the microbial composition in the rhizosphere. These findings offer a novel perspective and a promising candidate strain for enhancing Cd tolerance and prohibiting its accumulation in plants to reduce health risks associated with exposure to Cd-contaminated plants.

Cilengitide inhibits osteoclast adhesion through blocking the αvß3-mediated FAK/Src signaling pathway.

The remodeling of actin cytoskeleton of osteoclasts on the bone matrix is essential for osteoclastic resorption activity. A specific regulator of the osteoclast cytoskeleton, integrin αvß3, is known to provide a key role in the degradation of mineralized bone matrixes. Cilengitide is a potent inhibitor of integrins and is capable of affecting αvß3 receptors, and has anti-tumor and anti-angiogenic and apoptosis-inducing effects. However, its function on osteoclasts is not fully understood. Here, the cilengitide role on nuclear factor κB ligand-receptor activator (RANKL)-induced osteoclasts was explored. Cells were cultured with varying concentrations of cilengitide (0,0.002,0.2 and 20 µM) for 7 days, followed by detected via Cell Counting Kit-8, staining for tartrate resistant acid phosphatase (TRAP), F-actin ring formation, bone resorption assays, adhesion assays, immunoblotting assays, and real-time fluorescent quantitative PCR. Results demonstrated that cilengitide effectively restrained the functionality and formation of osteoclasts in a concentration-dependent manner, without causing any cytotoxic effects. Mechanistically, cilengitide inhibited osteoclast-relevant genes expression; meanwhile, cilengitide downregulated the expression of key signaling molecules associated with the osteoclast cytoskeleton, including focal adhesion kinase (FAK), integrin αvß3 and c-Src. Therefore, this results have confirmed that cilengitide regulates osteoclast activity by blocking the integrin αvß3 signal pathway resulting in diminished adhesion and bone resorption of osteoclasts.

Hydrogen peroxide reduces root cadmium uptake but facilitates root-to-shoot cadmium translocation in rice through modulating cadmium transporters.

Cadmium (Cd) contamination in agricultural soils has become a serious worldwide environmental problem threatening crop production and human health. Hydrogen peroxide (H2O2) is a critical second messenger in plant response to Cd exposure. However, its role in Cd accumulation in various organs of plants and the mechanistic basis of this regulation remains to be elucidated. In this study, we used electrophysiological and molecular approaches to understand how H2O2 regulates Cd uptake and translocation in rice plants. Our results showed that the pretreatment of H2O2 significantly reduced Cd uptake by rice roots, which was associated with the downregulation of OsNRAMP1 and OsNRAMP5. On the other hand, H2O2 promoted the root-to-shoot translocation of Cd, which might be attributed to the upregulation of OsHMA2 critical for Cd2+ phloem loading and the downregulation of OsHMA3 involved in the vacuolar compartmentalization of Cd2+, leading to the increased Cd accumulation in rice shoots. Furthermore, such regulatory effects of H2O2 on Cd uptake and translocation were notably amplified by the elevated level of exogenous calcium (Ca). Collectively, our results suggest that H2O2 can inhibit Cd uptake but increase root to shoot translocation through modulating the transcriptional levels of genes encoding Cd transporters, furthermore, application of Ca can amplify this effect. These findings will broaden our understanding of the regulatory mechanisms of Cd transport in rice plants and provide theoretical foundation for breeding rice for low Cd accumulation.

Analysis and validation of diagnostic biomarkers and immune cell infiltration characteristics in pediatric sepsis by integrating bioinformatics and machine learning.

BACKGROUND: Pediatric sepsis is a complicated condition characterized by life-threatening organ failure resulting from a dysregulated host response to infection in children. It is associated with high rates of morbidity and mortality, and rapid detection and administration of antimicrobials have been emphasized. The objective of this study was to evaluate the diagnostic biomarkers of pediatric sepsis and the function of immune cell infiltration in the development of this illness. METHODS: Three gene expression datasets were available from the Gene Expression Omnibus collection. First, the differentially expressed genes (DEGs) were found with the use of the R program, and then gene set enrichment analysis was carried out. Subsequently, the DEGs were combined with the major module genes chosen using the weighted gene co-expression network. The hub genes were identified by the use of three machine-learning algorithms: random forest, support vector machine-recursive feature elimination, and least absolute shrinkage and selection operator. The receiver operating characteristic curve and nomogram model were used to verify the discrimination and efficacy of the hub genes. In addition, the inflammatory and immune status of pediatric sepsis was assessed using cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT). The relationship between the diagnostic markers and infiltrating immune cells was further studied. RESULTS: Overall, after overlapping key module genes and DEGs, we detected 402 overlapping genes. As pediatric sepsis diagnostic indicators, CYSTM1 (AUC = 0.988), MMP8 (AUC = 0.973), and CD177 (AUC = 0.986) were investigated and demonstrated statistically significant differences (P < 0.05) and diagnostic efficacy in the validation set. As indicated by the immune cell infiltration analysis, multiple immune cells may be involved in the development of pediatric sepsis. Additionally, all diagnostic characteristics may correlate with immune cells to varying degrees. CONCLUSIONS: The candidate hub genes (CD177, CYSTM1, and MMP8) were identified, and the nomogram was constructed for pediatric sepsis diagnosis. Our study could provide potential peripheral blood diagnostic candidate genes for pediatric sepsis patients.

Capsicum Waste as a Sustainable Source of Capsaicinoids for Metabolic Diseases.

Capsaicinoids are pungent alkaloid compounds enriched with antioxidants, anti-microbial, anti-inflammatory, analgesics, anti-carcinogenic, anti-obesity and anti-diabetic properties. These compounds are primarily synthesised in the placenta of the fruit and then transported to other vegetative parts. Different varieties of capsicum and chillies contain different capsaicinoid concentrations. As capsicums and chillies are grown extensively throughout the world, their agricultural and horticultural production leads to significant amount of waste generation, in the form of fruits and plant biomass. Fruit wastes (placenta, seeds and unused fruits) and plant biowaste (stems and leaves) can serve as sources of capsaicinoids which can provide opportunities to extract these compounds for development of nutraceutical products using conventional or advanced extraction techniques. Capsaicin and dihydrocapsaicin are two most abundantly found pungent compounds. Considering the health benefits of capsaicinoids, these compounds can help in reducing metabolic disease complications. The development of an advanced encapsulation therapy of safe and clinically effective oral capsaicinoid/capsaicin formulation seem to require evaluation of strategies to address challenges related to the dosage, limited half-life and bioavailability, adverse effects and pungency, and the impacts of other ligands antagonising the major capsaicinoid receptor.

An miR156-regulated nucleobase-ascorbate transporter 2 confers cadmium tolerance via enhanced anti-oxidative capacity in barley.

INTRODUCTION: Cadmium (Cd) is one of the most detrimental heavy metal pollutants, seriously affecting crop production and human health. Nucleobase-ascorbic acid transporters (NAT) are widely present in many living organisms including plants, animals and microbes; however, the role of NAT in plant Cd tolerance remains unknown. OBJECTIVES: To identify Cd-induced miRNAs that target HvNAT2 and to determine the role of this gene and its product in Cd tolerance. METHODS: High-throughput-sequencing was used to identify the miRNA expression profile of barley roots in response to Cd stress. Overexpression (OX) and RNAi lines were then constructed for HvNAT2 and comparative transcriptomic analysis was performed to determine the function of this transporter examining its effects on traits such as Cd uptake/flux and translocation, morphology and antioxidant capacity in relation to Cd tolerance. In addition, phylogenetic analysis was performed to obtain insights into the evolution of HvNAT2. RESULTS: Cd stress-induced genome-wide expression profiles of miRNAs identified a Cd-induced miRNA, miR156g-3p_3, that had HvNAT2 as its target. HvNAT2 was negatively regulated in the high-Cd-accumulating and Cd-tolerant genotype Zhenong8. Evolutionary analysis indicated that orthologues of the plasma membrane localized, HvNAT2, can be traced back to the sister group of land plants, the streptophyte algae. Overexpression of HvNAT2 increases Cd tolerance with higher tissue Cd accumulation but less oxidative damage in transgenic barley plants. RNAi of HvNAT2 leads to a significant reduction of Cd tolerance. The higher Cd accumulation in roots of the OX3 line was also demonstrated by confocal microscopy and electrophysiology. Transcriptome analysis showed that the enhancement of antioxidant capacity by HvNAT2 was related to stress signaling pathways. Furthermore, oxidative stress tolerance in HvNAT2-OX plants was regulated by the synthesis of phytochelatins and the glutathione metabolism cycle. CONCLUSION: Our study reveals a key molecular mechanism of NAT in Cd tolerance in plants that is useful for sustainable agricultural production and management of hazardous this heavy metal for better environment management and ecosystem function.

Effects of different depth of anesthesia on perioperative inflammatory reaction and hospital outcomes in elderly patients undergoing laparoscopic radical gastrectomy.

BACKGROUND: To investigate the effect of different depth of anesthesia on inflammatory factors and hospital outcomes in elderly patients undergoing laparoscopic radical gastrectomy for gastric cancer, in order to select an appropriate depth of anesthesia to improve the prognosis of patients undergoing surgery and improve the quality of life of patients. METHODS: A total of 80 elderly patients aged 65 and above who underwent laparoscopic radical gastrectomy in our hospital were by convenience sampling and randomly divided into two groups : 55 groups ( group H ) and 45 groups ( group L ), 40 cases in each group. The depth of anesthesia was maintained using a closed-loop target-controlled infusion system: the EEG bispectral index was set to 55 in the H group and 45 in the L group. Venous blood samples were collected 2 h (T2), 24 h (T3) and 72 h (T4) after the start of surgery. The intraoperative dosage of propofol and remifentanil, operation duration, postoperative PACU stay time, intraoperative consciousness occurrence, postoperative hospital stay and postoperative pulmonary inflammatory events were recorded. RESULTS: The patient characteristic of the two groups had no statistical difference and were comparable (P > 0.05). The intraoperative dosage of propofol in group H was lower than that in group L (P < 0.05). Compared with the L group, the plasma IL-6 and IL-10 concentrations in the H group were significantly increased at T2 (P < 0.05), and the plasma IL-10 concentration was significantly increased at T4 (P < 0.05). The plasma concentrations of IL-6 and IL-10 were higher in both groups at T2, T3 and T4 than at T1, while at T4, the concentration of TNF-α in group H was higher than at T1 (P < 0.05). CONCLUSION: When the BIS value of the depth of anesthesia is 45, the perioperative release of inflammatory factors in elderly patients with laparoscopic radical gastrectomy for gastric cancer is less than BIS 55, and does not affect the prognosis.

Insight into the role of DPP-4 in fibrotic wound healing.

Wound healing is a complex and long-term process consisting of hemostasis, inflammation, proliferation, and maturation/remodeling. These four stages overlap and influence each other; they affect wound healing in different ways, and if they do not function perfectly, they may cause scarring, proliferative scarring and keloid formation. A therapeutic target affecting wound healing in multiple ways will help the healing process proceed more effectively. DPP-4/CD26 is a multifunctional dimorphic glycoprotein widely distributed on the surface of a variety of cells, including fibroblasts and keratin-forming cells. It has been found to affect periwound inflammation, re-epithelialization, extracellular matrix secretion and skin fibrosis and is a potential target for promoting wound healing and inhibiting scar formation. After presenting a brief introduction of the wound healing process and DPP-4/CD26, this paper summarizes the effects of DPP-4/CD26 on cells involved in different stages of wound healing and discusses the feasibility of DPP-4/CD26 as a multifunctional target for the treatment of wound healing and inhibition of scar formation.

The ASIC3-M-CSF-M2 macrophage-positive feedback loop modulates fibroblast-to-myofibroblast differentiation in skin fibrosis pathogenesis.

Inflammation is one of the main pathological features leading to skin fibrosis and a key factor leading to the progression of skin fibrosis. Acidosis caused by a decrease in extracellular pH is a sign of the inflammatory process. Acid-sensing ion channels (ASICs) are ligand-gated ion channels on the cell membrane that sense the drop in extracellular pH. The molecular mechanisms by which skin fibroblasts are regulated by acid-sensing ion channel 3 (ASIC3) remain unknown. This study investigated whether ASIC3 is related to inflammation and skin fibrosis and explored the underlying mechanisms. We demonstrate that macrophage colony-stimulating factor (M-CSF) is a direct target of ASIC3, and ASIC3 activation promotes M-CSF transcriptional regulation of macrophages for M2 polarization. The polarization of M2 macrophages transduced by the ASIC3-M-CSF signal promotes the differentiation of fibroblasts into myofibroblasts through transforming growth factor ß1 (TGF-ß1), thereby producing an ASIC3-M-CSF-TGF-ß1 positive feedback loop. Targeting ASIC3 may be a new treatment strategy for skin fibrosis.

Stress signaling convergence and nutrient crosstalk determine zinc-mediated amelioration against cadmium toxicity in rice.

Consumption of rice (Oryza sativa L.) is one of the major pathways for heavy metal bioaccumulation in humans over time. Understanding the molecular responses of rice to heavy metal contamination in agriculture is useful for eco-toxicological assessment of cadmium (Cd) and its interaction with zinc (Zn). In certain crops, the impacts of Cd stress or Zn nutrition on the biophysical chemistry and gene expression have been widely investigated, but their molecular interactions at transcriptomic level, particularly in rice roots, are still elusive. Here, hydroponic investigations were carried out with two rice genotypes (Yinni-801 and Heizhan-43), varying in Cd contents in plant tissues to determine their transcriptomic responses upon Cd15 (15 µM) and Cd15+Zn50 (50 µM) treatments. High throughput RNA-sequencing analysis confirmed that 496 and 2407 DEGs were significantly affected by Cd15 and Cd15+Zn50, respectively, among which 1016 DEGs were commonly induced in both genotypes. Multitude of DEGs fell under the category of protein kinases, such as calmodulin (CaM) and calcineurin B-like protein-interacting protein kinases (CBL), indicating a dynamic shift in hormonal signal transduction and Ca2+ involvement with the onset of treatments. Both genotypes expressed a mutual regulation of transcription factors (TFs) such as WRKY, MYB, NAM, AP2, bHLH and ZFP families under both treatments, whereas genes econding ABC transporters (ABCs), high affinity K+ transporters (HAKs) and Glutathione-S-transferases (GSTs), were highly up-regulated under Cd15+Zn50 in both genotypes. Zinc addition triggered more signaling cascades and detoxification related genes in regulation of immunity along with the suppression of Cd-induced DEGs and restriction of Cd uptake. Conclusively, the effective integration of breeding techniques with candidate genes identified in this study as well as economically and technologically viable methods, such as Zn nutrient management, could pave the way for selecting cultivars with promising agronomic qualities and reduced Cd for sustainable rice production.

The Effect of Oxycodone on Post-operative Pain and Inflammatory Cytokine Release in Elderly Patients Undergoing Laparoscopic Gastrectomy.

Background: To evaluate the effect of oxycodone on post-operative pain and inflammation in elderly patients undergoing laparoscopic gastrectomy. Methods: Sixty patients who were of both sexes, American Society of Anesthesiologists Physical Status (ASA-PS) Class I or II, over 65 years of age and undergoing an elective laparoscopic radical gastrectomy were randomly divided into two groups: an oxycodone group (Group O) including 20 males and 10 females and a sufentanil group (Group S) including 21 males and 9 females. The post-operative analgesia regimen was as follows: 40 mg of parecoxib sodium and 0.1 mg/kg of oxycodone was intravenously injected into Group O before the abdomen closure, while 40 mg of parecoxib sodium and 0.1 µg/kg of sufentanil was injected intravenously into Group S. Both groups were infiltrated with 20 ml of 1% ropivacaine at the end of the operation. The level of serum IL-6 and IL-10 were assayed immediately at the following timepoints: at the conclusion of surgery (T1), 1 h (T2), 6 h (T3), and 24 h (T4) after the completion of the surgery. The numerical rating scale (NRS), the Ramsay sedation score, analgesic-related adverse events, post-operative pulmonary inflammation events and the post-operative stay were recorded. Results: Compared with Group S, the serum IL-6 concentrations of Group O decreased at T3 and T4, while the serum IL-10 concentrations increased (P < 0.05). In Group O, the serum IL-6 concentrations at T3 and T4 were lower than those at T1 (P < 0.05). The incidence of post-operative nausea and vomiting (PONV) and pulmonary inflammation in Group O was lower than that in Group S (P < 0.05). At each time point, the NRS of visceral pain in Group O was lower than that in Group S. At 6 and 24 h after extubation, the NRS of incision pain in Group O was lower than that in Group S (P < 0.05). Conclusion: Oxycodone can regulate the level of inflammatory cytokines and reduce post-operative inflammatory response.

YAP/STAT3 promotes the immune escape of larynx carcinoma by activating VEGFR1-TGFß signaling to facilitate PD-L1 expression in M2-like TAMs.

Larynx carcinoma (LC) is the most prevalent head and neck cancer among adults. LC xenograft mouse model was generated to verify the effect of VEGF on macrophage polarization and tumor growth in vivo. EdU assay was performed to measure the cell proliferation. Transwell assay was applied to assess cell migration. The expression of YAP and STAT3 was also significantly increased in LC tumor tissues. Moreover, both YAP and STAT3 overexpression in LC cells promoted the proliferation, migration, as well as the secretion of PD-L1 in M2-like TAMs. Mechanistically, the interaction between YAP and STAT3 facilitated the transcription of VEGF. Moreover, with a co-culture system, VEGF secretion in LC cells enhanced PD-L1 expression in M2-like TAMs via activating VEGFR1-TGFß signaling pathway. Furthermore, VEGF secreted from LC cells also promoted the tumor growth of LC in vivo. We revealed that dysregulated YAP/STAT3 activity in LC cells could enhance the secretion of VEGF, which then functioned on M2-like TAMs via activating VEGFR1-TGFßß pathway to promote the expression of PD-L1 and immunosuppressive function of M2-like TAMs. Therefore, VEGF and PD-L1 might have a pivotal crosstalk between M2-like TAMs and LC cells, which provided a novel therapeutic target in regulating the metastasis of LC in future.

Highly Conserved Evolution of Aquaporin PIPs and TIPs Confers Their Crucial Contribution to Flowering Process in Plants.

Flowering is the key process for the sexual reproduction in seed plants. In gramineous crops, the process of flowering, which includes the actions of both glume opening and glume closing, is directly driven by the swelling and withering of lodicules due to the water flow into and out of lodicule cells. All these processes are considered to be controlled by aquaporins, which are the essential transmembrane proteins that facilitate the transport of water and other small molecules across the biological membranes. In the present study, the evolution of aquaporins and their contribution to flowering process in plants were investigated via an integration of genome-wide analysis and gene expression profiling. Across the barley genome, we found that HvTIP1;1, HvTIP1;2, HvTIP2;3, and HvPIP2;1 were the predominant aquaporin genes in lodicules and significantly upregulated in responding to glume opening and closing, suggesting the importance of them in the flowering process of barley. Likewise, the putative homologs of the above four aquaporin genes were also abundantly expressed in lodicules of the other monocots like rice and maize and in petals of eudicots like cotton, tobacco, and tomato. Furthermore, all of them were mostly upregulated in responding to the process of floret opening, indicating a conserved function of these aquaporin proteins in plant flowering. The phylogenetic analysis based on the OneKP database revealed that the homologs of TIP1;1, TIP1;2, TIP2;3, and PIP2;1 were highly conserved during the evolution, especially in the angiosperm species, in line with their conserved function in controlling the flowering process. Taken together, it could be concluded that the highly evolutionary conservation of TIP1;1, TIP1;2, TIP2;3 and PIP2;1 plays important roles in the flowering process for both monocots and eudicots.

Evolution of rapid blue-light response linked to explosive diversification of ferns in angiosperm forests.

Ferns appear in the fossil record some 200 Myr before angiosperms. However, as angiosperm-dominated forest canopies emerged in the Cretaceous period there was an explosive diversification of modern (leptosporangiate) ferns, which thrived in low, blue-enhanced light beneath angiosperm canopies. A mechanistic explanation for this transformative event in the diversification of ferns has remained elusive. We used physiological assays, transcriptome analysis and evolutionary bioinformatics to investigate a potential connection between the evolution of enhanced stomatal sensitivity to blue light in modern ferns and the rise of angiosperm-dominated forests in the geological record. We demonstrate that members of the largest subclade of leptosporangiate ferns, Polypodiales, have significantly faster stomatal response to blue light than more ancient fern lineages and a representative angiosperm. We link this higher sensitivity to levels of differentially expressed genes in blue-light signaling, particularly in the cryptochrome (CRY) signaling pathway. Moreover, CRYs of the Polypodiales examined show gene duplication events between 212.9-196.9 and 164.4-151.8 Ma, when angiosperms were emerging, which are lacking in other major clades of extant land plants. These findings suggest that evolution of stomatal blue-light sensitivity helped modern ferns exploit the shady habitat beneath angiosperm forest canopies, fueling their Cretaceous hyperdiversification.

An ATP binding cassette transporter HvABCB25 confers aluminum detoxification in wild barley.

Aluminum (Al) stress in acid soils is one of the major factors limiting crop productivity. ATP binding cassette (ABC) transporters have numerous roles in plants, but the link between ABCB protein subfamily and plant Al tolerance is still elusive. Here, we identified and characterized a novel tonoplast HvABCB25 in barley root cells. HvABCB25 was up-regulated in the transcriptome of Al-tolerant wild barley XZ16 under Al treatment and was highly Al-inducible in root tips. ABCB25 is originated from Streptophyte algae and evolutionarily conserved in land plants. Moreover, silencing HvABCB25 in Al-tolerant XZ16 led to significant suppression of Al tolerance as indicated by significantly reduced root growth and enhanced Al accumulation in root cells. Conversely, HvABCB25-overexpressed plants and Golden Promise showed similar Al content in whole roots and in cell sap, but the overexpression lines exhibited significantly higher Al-induced relative root growth and dry weight. Al florescence in cytosol of root cells were significantly less in overexpression lines than that in GP. These results indicated that overexpressing HvABCB25 may be responsible for Al detoxification via vacuolar Al sequestration in barley roots, providing useful insight into the genetic basis for a new Al detoxification mechanism towards plant Al tolerance in acid soils.

Treating the primary in low burden metastatic prostate cancer: Where do we stand?

ABSTRACT: On the basis of endocrine therapy for patients with low burden metastatic prostate cancer (LBMP), the clinical efficacy and quality of life were compared between prostate-only directed radiotherapy (PODT) and prostate and metastasis radiotherapy (PMRT).From November 2009 to November 2015, total 91 patients newly diagnosed with LBMP were retrospectively analyzed, of which 52 patients received PODT and 39 patients received PMRT. The biochemical failure free interval (IBF), prostate specific survival (PCSS), and overall survival (OS) time were compared between the 2 groups, and expanded prostate cancer index composite (EPIC) scale was used to evaluate the difference in quality of life between the 2 groups.The median IBF of the PODT group was 31 months, which was significantly lower than the 39 months of the PMRT group (P < .05); the 5-year OS and PCSS were 58.9%, 65.3% in PODT group, and 58.9%, 71.79% in PMRT group, respectively. There was no significant between the 2 groups (P > .05); the side effects of acute radiotherapy in PMRT group were significantly higher than PODT group (P < .05), especially in bone marrow suppression and gastrointestinal reactions; The scores of urinary system function and intestinal system function in PMRT group were significantly higher than PODT group at the end of radiotherapy, 3 months after radiotherapy, and 6 months after radiotherapy (P < .05). The score of sexual function in PMRT group was significantly lower than that in PODT group after radiotherapy (P < .05), and higher than that in PORT group at other follow-up time points (P < .05). The hormone function was decreased at each follow-up time point in 2 groups, and there was no significant difference between the 2 groups (P > .05).Patients with LBMP receiving PMRT can improve IBF, but cannot increase PCSS and OS, and increase the incidence of acute radiation injury.