Selective degradation of PL2L60 by metabolic stresses­induced autophagy suppresses multi­cancer growth.

It has been reported that PL2L60 proteins, a product of PIWIL2 gene which might be activated by an intragenic promoter, could mediate a common pathway specifically for tumorigenesis. In the present study, it was further identified by using western blot assay that the PL2L60 proteins could be degraded in cancer cells through a mechanism of selective autophagy in response to oxidative stress. The PL2L60 was downregulated in various types of cancer cells under the hypoxic condition independently of HIF­1α, resulting in apoptosis of cancer cells. Inhibition of autophagy by small interfering RNA targeting of either Beclin­1 (BECN1) or Atg5 resulted in restoration of PL2L60 expression in hypoxic cancer cell. The hypoxic degradation of PL2L60 was also blocked by the attenuation of the autophagosome membrane protein Atg8/microtubule­associated protein 1 light chain 3 (LC3) or autophagy cargo protein p62 expression. Surprisingly, Immunofluorescence analysis demonstrated that LC3 could be directly bound to PL2L60 and was required for the transport of PL2L60 from the nucleus to the cytoplasm for lysosomal flux under basal or activated autophagy in cancer cells. Moreover, flow cytometric analysis displayed that knocking down of PL2L60 mRNA but not PIWIL2 mRNA effectively inhibited cancer cell proliferation and promoted apoptosis of cancer cells. The similar results were obtained from in vivo tumorigenic experiment, in which PL2L60 downregulation in necroptosis areas was confirmed by immunohistochemistry. These results suggested that various cancer could be suppressed by promoting autophagy. The present study revealed a key role of autophagic degradation of PL2L60 in hypoxia­induced cancer cell death, which could be used as a novel therapeutic target of cancer.

LncRNA CALML3-AS1 modulated by m6A modification induces BTNL9 methylation to drive non-small-cell lung cancer progression.

Non-small cell lung cancer (NSCLC) is a common and lethal malignancy. The carcinogenic roles of lncRNA CALML3 antisense RNA 1 (CALML3-AS1) have been documented. However, the function and potential mechanisms of CALML3-AS1 in the progression of NSCLC need to be further explored. The molecule expression was assessed by qRT-PCR and Western blot. The subcellular localization of CALML3-AS1 was observed by fluorescence in situ hybridization (FISH). The malignant behaviors of NSCLC cells were evaluated by CCK-8, colony formation, EdU, wound healing and transwell assays. In vivo xenograft tumor and liver metastatic models were established. The molecular mechanisms were investigated by RIP, RNA pull-down and ChIP assays. The methylation level was detected by MSP. Herein, we found that CALML3-AS1 was upregulated, while butyrophilin-like 9 (BTNL9) was downregulated in NSCLC. Functionally, CALML3-AS1 depletion repressed NSCLC cell malignant phenotypes, in vivo tumor growth, and liver metastasis. Mechanistically, AlkB homolog 5 (ALKBH5) enhanced CALML3-AS1 stability via N6-methyladenosine (m6A) demethylation, whereas m6A reader YTH domain-containing 2 (YTHDC2) destabilized CALML3-AS1. Moreover, CALML3-AS1 inhibited BTNL9 transcription and expression through the recruitment of Zeste homolog 2 (EZH2). Rescue experiments demonstrated that BTNL9 downregulation counteracted sh-CALML3-AS1-mediated antitumor effects on NSCLC. Taken together, CALML3-AS1 modulated by ALKBH5 and YTHDC2 in an m6A modification dependent manner drives NSCLC progression via epigenetically repressing BTNL9.

Evolutionary roles of polyploidization-derived structural variations in the phenotypic diversification of Panax species.

Genomic structural variations (SVs) are widespread in plant and animal genomes and play important roles in phenotypic novelty and species adaptation. Frequent whole genome duplications followed by (re)diploidizations have resulted in high diversity of genome architecture among extant species. In this study, we identified abundant genomic SVs in the Panax genus that are hypothesized to have occurred through during the repeated polyploidizations/(re)diploidizations. Our genome-wide comparisons demonstrated that although these polyploidization-derived SVs have evolved at distinct evolutionary stages, a large number of SV-intersecting genes showed enrichment in functionally important pathways related to secondary metabolites, photosynthesis and basic cellular activities. In line with these observations, our metabolic analyses of these Panax species revealed high diversity of primary and secondary metabolites both at the tissue and interspecific levels. In particular, genomic SVs identified at ginsenoside biosynthesis genes, including copy number variation and large fragment deletion, appear to have played important roles in the evolution and diversification of ginsenosides. A further herbivore deterrence experiment demonstrated that, as major triterpenoidal saponins found exclusively in Panax, ginsenosides provide protection against insect herbivores. Our study provides new insights on how polyploidization-derived SVs have contributed to phenotypic novelty and plant adaptation.

[Effects of Silicon Application on Arsenic Sequestration in Iron Plaque and Arsenic Translocation in Rice].

The As sequestration by iron plaque and the As translocation in rice significantly affect the As accumulation in brown rice, and silicon (Si) application inhibits the As accumulation in rice plants. However, little information is available concerning the effect of Si application on As sequestration by iron plaque and translocation in rice. In this study, a pot experiment using As-contaminated paddy soil with different Si supply levels was conducted to investigate the effects of Si application on the As sequestration by iron plaque on the root surface and the As translocation from different tissues to brown rice. The results showed that the Si2 (0.66 g·kg-1) treatment significantly increased the activities of CAT (1.81 times), SOD (7.98 times), and POD (1.25 times) in the roots, increased the DCB-extractable Fe concentration (44.35%), and promoted the roughness of iron plaque (108.91%), resulting in a significant increase in the DCB-extractable As concentration of iron plaque (88.32%). Moreover, the Si2 treatment significantly promoted the As accumulation in the roots and inhibited the As translocation from the roots and leaves to the brown rice, leading to a significant decrease in the brown rice As concentration (53.12%). The increase in As sequestration by iron plaque with Si application was attributed to the enhancement of iron plaque formation and the promotion of surface roughness of iron plaque, whereas the inhibition of As translocation from the roots and leaves to the brown rice in the Si application treatment was closely related to the competition between Si with As for transporters and the promotion of As-thiol complex formation and As compartmentalization in vacuolar. These findings provide more insight into the mechanisms of As translocation in rice and will be helpful for exploring strategies to reduce rice grain As through Si supply in As-contaminated paddy fields in South China.

m6A methyltransferase METTL3-induced lncRNA SNHG17 promotes lung adenocarcinoma gefitinib resistance by epigenetically repressing LATS2 expression.

Gefitinib has been widely applied for the treatment of lung adenocarcinoma (LUAD). However, the long-term application of gefitinib usually leads to acquired drug resistance in tumour patients, resulting in clinical treatment failure. Small nucleolar host gene 17 (SNHG17) has been shown to play a regulatory role in LUAD progression. Nevertheless, the role of SNHG17 in LUAD gefitinib resistance remains elusive. The expression pattern of SNHG17 was examined in tissues and cell lines of gefitinib-sensitive and gefitinib-resistant LUAD, respectively. Gain- and loss-of-function experiments were employed to assess the biological functions of SNHG17 in cell proliferation and apoptosis, as well as aggressive phenotypes of LUAD cells. MeRIP-qPCR and colorimetric quantificational analysis were performed to detect m6A modifications and contents. Fluorescence in situ hybridisation (FISH) and subcellular fractionation analysis were used to reveal the distribution of SNHG17. RIP and ChIP assays were performed to further validate the SNHG17/EZH2/LATS2 regulatory axis. A xenograft tumour growth assay was conducted to evaluate the role of SNHG17 in LUAD gefitinib resistance in vivo. SNHG17 was upregulated in gefitinib-resistant LUAD tissues and cell lines. Functional assays showed that SNHG17 aggravated the malignant phenotypes of gefitinib-resistant LUAD cells. In addition, METTL3-mediated N6-methyladenosine modification could induce the upregulation of SNHG17by stabilising its RNA transcript. Mechanistically, SNHG17 epigenetically repressed the expression of LATS2 by recruiting EZH2 to the promoter region of LATS2. The regulatory role of the SNHG17/EZH2/LATS2 axis in LUAD gefitinib resistance was further supported in vivo. Collectively, our findings suggested that SNHG17 induced by METTL3 could promote LUAD gefitinib resistance by epigenetically repressing LATS2 expression.

Reshuffling of the ancestral core-eudicot genome shaped chromatin topology and epigenetic modification in Panax.

All extant core-eudicot plants share a common ancestral genome that has experienced cyclic polyploidizations and (re)diploidizations. Reshuffling of the ancestral core-eudicot genome generates abundant genomic diversity, but the role of this diversity in shaping the hierarchical genome architecture, such as chromatin topology and gene expression, remains poorly understood. Here, we assemble chromosome-level genomes of one diploid and three tetraploid Panax species and conduct in-depth comparative genomic and epigenomic analyses. We show that chromosomal interactions within each duplicated ancestral chromosome largely maintain in extant Panax species, albeit experiencing ca. 100-150 million years of evolution from a shared ancestor. Biased genetic fractionation and epigenetic regulation divergence during polyploidization/(re)diploidization processes generate remarkable biochemical diversity of secondary metabolites in the Panax genus. Our study provides a paleo-polyploidization perspective of how reshuffling of the ancestral core-eudicot genome leads to a highly dynamic genome and to the metabolic diversification of extant eudicot plants.

A novel tumor-specific broad-spectral monoclonal antibody to PL2L60 is highly effective for the treatment of various types of cancers from human and mouse.

There are numerous antibodies used for cancer therapy in clinic, but they are essentially less efficacy than expected. None of them has tumor-specific and broad-spectral properties. PIWIL2-like (PL2L) protein 60 (PL2L60) is a product of alienated activation of PIWIL2 gene, and has been found to be specifically and widely expressed in various types of cancers, including hematopoietic and solid ones. Current study aims to investigate whether a monoclonal antibody (mAb) to PL2L60 has both tumor-specific and broad-spectral properties, which can be used universally to treat various types of cancers. The expression of PL2L60 protein in the cell surface and cytoplasm were determined in a panel of human and mouse tumor cell lines by flow cytometry, immunofluorescent microscopy and Western Blotting. The apoptosis and the cell cycle arrest of the tumor cells treated with mAb KAO3 were evaluated by flow cytometry. The tumorigenesis of the mAb KAO3-pretreated tumor cells was determined by tumor incidence and tumor size, and the efficacy of mAb KAO3 treatment on tumor growth in tumors-bearing mice were kinetically evaluated. Complement-dependent cytotoxicity (CDC) assay was used to determine the capacity of mAb KAO3 to kill tumor cells. Treatment of human or mouse tumor cells from hematopoietic or solid tumors with mAb KAO3 at the time of inoculation efficiently inhibited tumorigenesis in the severe combined immunodeficient (SCID) mice. Moreover, injection of mAb KAO3 into established tumors significantly inhibited their growth, and prolonged survival of the tumor-bearing mice, including lymphoma, breast cancer, lung cancer and cervical cancer. The efficacy of mAb KAO3 treatment is likely associated with its binding to PL2L60 expressed on tumor cell surface, which may lead to cancer cell death through blocking cell cycling and/or activation of complement. In conclusion, we have identified a tumor-specific mAb to PL2L60 (KAO3), which may be used potentially to treat all the types of human cancers including from both hematopoietic and solid ones.

Genome sequences of five Sitopsis species of Aegilops and the origin of polyploid wheat B subgenome.

Common wheat (Triticum aestivum, BBAADD) is a major staple food crop worldwide. The diploid progenitors of the A and D subgenomes have been unequivocally identified; that of B, however, remains ambiguous and controversial but is suspected to be related to species of Aegilops, section Sitopsis. Here, we report the assembly of chromosome-level genome sequences of all five Sitopsis species, namely Aegilops bicornis, Ae. longissima, Ae. searsii, Ae. sharonensis, and Ae. speltoides, as well as the partial assembly of the Amblyopyrum muticum (synonym Aegilops mutica) genome for phylogenetic analysis. Our results reveal that the donor of the common wheat B subgenome is a distinct, and most probably extinct, diploid species that diverged from an ancestral progenitor of the B lineage to which the still extant Ae. speltoides and Am. muticum belong. In addition, we identified interspecific genetic introgressions throughout the evolution of the Triticum/Aegilops species complex. The five Sitopsis species have various assembled genome sizes (4.11-5.89 Gb) with high proportions of repetitive sequences (85.99%-89.81%); nonetheless, they retain high collinearity with other genomes or subgenomes of species in the Triticum/Aegilops complex. Differences in genome size were primarily due to independent post-speciation amplification of transposons. We also identified a set of Sitopsis genes pertinent to important agronomic traits that can be harnessed for wheat breeding. These newly assembled genome resources provide a new roadmap for evolutionary and genetic studies of the Triticum/Aegilops complex, as well as for wheat improvement.

New Biologics for the Treatment of Atopic Dermatitis: Analysis of Efficacy, Safety, and Paradoxical Atopic Dermatitis Acceleration.

Atopic dermatitis (AD) is a chronic, inflammatory skin disease with an eczematous rash and itching. Due to undesired adverse effects of traditional systemic treatment, there is still an unmet need for safe and effective long-term therapy for refractory AD. As our understanding of the pathogenesis underlying AD grows, novel treatments targeting specific molecules have been developed. Here, we discuss the efficacy and safety profiles of these drugs in recent clinical trials. Among their adverse effects, of particular note is AD acceleration. Although there is still debate about whether certain adverse reactions can be said to be paradoxical adverse events (PAEs), a wide range of PAEs have been reported during biological treatment for chronic immune-mediated diseases. Close surveillance of novel biologics is crucial to detect new undescribed paradoxical reactions and to shed light on the convoluted pathogenesis of AD.

Efficacy and Safety of Giant Condyloma Acuminatum with Monotherapy of Topical Traditional Chinese Medicine: Report of Eight Cases.

BACKGROUND: Giant condyloma acuminatum (GCA), also called Buschke-Löwenstein tumor, presents as a verrucous infiltrating lesion and is caused by sexual transmission of human papilloma virus. The optimal treatment is controversial and there are no standard guidelines because of its rarity and frequent recurrence. It has a relatively high local recurrence rate. OBJECTIVE: We here report eight patients (six men and two women) with GCA whose lesions were successfully treated topically with traditional Chinese medicine (TCM) preparations, paiteling. METHODS AND MATERIALS: We administered topical TCM preparations to eight patients diagnosed with GCA who had refused surgery. The treatment process included three stages, their durations depending on the speed of resolution of the lesions and the results of visual inspection with acetic acid. RESULTS: No significant complications occurred in any patient. The functional and esthetic outcomes were satisfactory. No recurrences were detected during follow-up. CONCLUSION: Topical treatment with TCM preparations may be a good alternative to surgery or other traditional methods for the treatment of GCA. This treatment has the advantages of being non-invasive, painless, and having a low risk of recurrence, and may be a useful adjunct to mainstream medical treatments.

A drought-responsive rice amidohydrolase is the elusive plant guanine deaminase with the potential to modulate the epigenome.

Drought stress in plants causes differential expression of numerous genes. One of these differentially expressed genes in rice is a specific amidohydrolase. We characterized this amidohydrolase gene on the rice chromosome 12 as the first plant guanine deaminase (OsGDA1). The biochemical activity of GDA is known from tea and coffee plants where its catalytic product, xanthine, is the precursor for theine and caffeine. However, no plant gene that is coding for GDA is known so far. Recombinant OsGDA1 converted guanine to xanthine in vitro. Measurement of guanine and xanthine contents in the OsGDA1 knockout (KO) line and in the wild type Tainung 67 rice plants also suggested GDA activity in vivo. The content of cellular xanthine is important because of its catabolic products allantoin, ureides, and urea which play roles in water and nitrogen stress tolerance among others. The identification of OsGDA1 fills a critical gap in the S-adenosyl-methionine (SAM) to xanthine pathway. SAM is converted to S-adenosyl-homocysteine (SAH) and finally to xanthine. SAH is a potent inhibitor of DNA methyltransferases, the reduction of which leads to increased DNA methylation and gene silencing in Arabidopsis. We report that the OsGDA1 KO line exhibited a decrease in SAM, SAH and adenosine and an increase in rice genome methylation. The OsGDA1 protein phylogeny combined with mutational protein destabilization analysis suggested artificial selection for null mutants, which could affect genome methylation as in the KO line. Limited information on genes that may affect epigenetics indirectly requires deeper insights into such a role and effect of purine catabolism and related genetic networks.

Evolutionary Contribution of Duplicated Genes to Genome Evolution in the Ginseng Species Complex.

Genes duplicated by whole genome duplication (WGD) and small-scale duplication (SSD) have played important roles in adaptive evolution of all flowering plants. However, it still remains underinvestigated how the distinct models of duplication events and their contending evolutionary patterns have shaped the genome and epigenomes of extant plant species. In this study, we investigated the contribution of the WGD- and SSD-derived duplicate genes to the genome evolution of one diploid and three closely related allotetraploid Panax species based on genome, methylome, and proteome data sets. Our genome-wide comparative analyses revealed that although the ginseng species complex was recently diverged, they have evolved distinct overall patterns of nucleotide variation, cytosine methylation, and protein-level expression. In particular, genetic and epigenetic asymmetries observed in the recent WGD-derived genes are largely consistent across the ginseng species complex. In addition, our results revealed that gene duplicates generated by ancient WGD and SSD mechanisms exhibited distinct evolutionary patterns. We found the ancient WGD-derived genes (i.e., ancient collinear gene) are genetically more conserved and hypomethylated at the cytosine sites. In contrast, some of the SSD-derived genes (i.e., dispersal duplicated gene) showed hypermethylation and high variance in nucleotide variation pattern. Functional enrichment analyses of the duplicated genes indicated that adaptation-related traits (i.e., photosynthesis) created during the distant ancient WGDs are further strengthened by both the more recent WGD and SSD. Together, our findings suggest that different types of duplicated genes may have played distinct but relaying evolutionary roles in the polyploidization and speciation processes in the ginseng species complex.

[Effects of Ferrous Sulfate and Ferric Nitrate on Cadmium Transportation in the Rhizosphere Soil-Rice System].

Cadmium (Cd) contamination in the agricultural soils of China is a serious and growing environmental problem that urgently needs to be controlled and completely remediated. The biogeochemical cycles of nitrogen (N), sulfur (S), and iron (Fe), and the coupled cycles of Fe-N and Fe-S have been reported to control Cd transportation in the soil-rice system. Exploring practical remediation strategies for Cd from the perspective of the application of nutrients such as N, S, and Fe for rice growth is expected to obtain farm-specific and state-of-the-art technologies and products to reduce the accumulation of Cd in rice grains. Using our earlier study as a basis, the rhizosphere bag-pot experiment with ferrous sulfate (FeSO4) and ferric nitrate[Fe(NO3)3] treatments was conducted to investigate Cd bioavailability in rhizosphere soil and Cd translocation in rice plants, and to highlight some possible factors and mechanisms controlling Cd accumulation in rice grains. The results showed that both FeSO4 and Fe(NO3)3 treatments reduced the bioavailable Cd (NH4Ac-Cd) content in rhizosphere soil, with the decreasing extent being significantly lower in the former (55.6%) than in the latter (76.0%). Both FeSO4 and Fe(NO3)3 treatments changed the distribution characteristics of Cd in rice tissues, and the FeSO4 treatment increased the Cd content in brown rice (0.6 mg·kg-1), but the Fe(NO3)3 treatment decreased the Cd content in brown rice (0.1 mg·kg-1). Adsorption or co-precipitation of Cd by iron plaque, increased accumulations of Cd in root, stem, and leaf, and enhanced translocations of Cd from root, stem, and nodule to brown rice occurred with the increased Cd content in brown rice of the FeSO4 treatment. However, the decreased Cd content in brown rice with the Fe(NO3)3 treatment was ascribed to adsorption or co-precipitation of Cd by poorly crystalline Fe oxides and solid Fe sulfides, decreased accumulations of Cd in stem and nodule, and weakened translocations of Cd from root, leaf, and nodule to brown rice. These findings provide a scientific basis for the exploration and application of nutritive soil amendment, and will have significance in regards to the remediation of Cd-contaminated agricultural soils in China.

Morphological and Transcriptome Analyses Provide Insights into Growth Inhibition of Trichophyton rubrum Caused by Laser Irradiation.

Trichophyton rubrum is one of the most common types of dermatophyte, causing superficial skin mycosis in human populations. Although laser treatment of onychomycosis has been proven to be effective in the clinic, the underlying mechanism of the effect of the laser on fungal growth is not clear. The objective of the present study was to observe the ultrastructural changes of Trichophyton rubrum following laser irradiation and compare the transcriptome differences between the laser irradiation group and control group. In the present study, scanning electron microscopy and transmission electron microscopy were used to observe the ultrastructural changes following the laser irradiation of Trichophyton rubrum. We also performed RNA-seq to investigate the effects of laser irradiation on Trichophyton rubrum by comparing the transcriptome pattern with the control. Morphological observation with electron microscopy indicated that laser irradiation resulted in the destruction of the cell membrane system. A significant induction of apoptosis was noted compared with the control group, which was confirmed by the formation of the myeloid body and protein aggregates in the cytoplasm. RNA-seq demonstrated that the expression levels of Acyl-CoA N-acyltransferase and S-adenosyl-L-methionine-dependent methyltransferase were increased in the laser irradiation group. This result indicated that laser irradiation triggered the initiation of the damage repair pathway. In conclusion, the present study suggested that laser irradiation caused physiological injury and therefore inhibited the growth of Trichophyton rubrum.

Different Numbers of Long-Pulse 1064-nm Nd-YAG Laser Treatments for Onychomycosis: A Pilot Study.

PURPOSE: To examine the benefits of different numbers of 1064-nm Nd-YAG laser treatments in patients with onychomycosis. METHODS: This was a pilot study of patients with onychomycosis who were divided into three groups: four treatment sessions (group A), eight sessions (group B), and 12 sessions (group C). Only infected nails of degrees II-III (Scoring Clinical Index for Onychomycosis) were included. Treatment was given once a week using a long-pulse Nd-YAG 1064-nm laser. Patients were followed at 8, 16, and 24 weeks after the first treatment. Side effects were recorded. RESULTS: Treatments were completed for 442 nails in 102 patients. The efficacy rates at 8, 16, and 24 weeks were 35.5%, 38.7%, and 37.4% for group A; 31.4%, 41.7%, and 44.0% for group B; and 27.7%, 50.0%, and 55.4% for group C, respectively. There was a significant difference in the efficacy rate at 24 weeks (P = 0.016) between groups A and C, but not for groups A vs. B, or for groups B vs. C. No difference in the efficacy rate at 8 or 16 weeks was observed among the three groups. In all three groups, the efficacy was better for degree II nails than for degree III nails (all P = 0.016) between groups A and C, but not for groups A vs. B, or for groups B vs. C. No difference in the efficacy rate at 8 or 16 weeks was observed among the three groups. In all three groups, the efficacy was better for degree II nails than for degree III nails (all. CONCLUSIONS: The 1064-nm Nd-YAG laser had clinical benefits against onychomycosis. Higher numbers of treatments provided better long-term (24-week) benefits, but had no impact on the short-term outcomes. The efficacy of laser treatment on degree II onychomycosis was better than for degree III.

Pentamidine inhibits prostate cancer progression via selectively inducing mitochondrial DNA depletion and dysfunction.

OBJECTIVES: We investigated the anti-cancer activity of pentamidine, an anti-protozoal cationic aromatic diamidine drug, in prostate cancer cells and aimed to provide valuable insights for improving the efficacy of prostate cancer treatment. MATERIALS AND METHODS: Prostate cancer cell lines and epithelial RWPE-1 cells were used in the study. Cell viability, wound-healing, transwell and apoptosis assays were examined to evaluate the influences of pentamidine in vitro. RNA-seq and qPCR were performed to analyse changes in gene transcription levels upon pentamidine treatment. Mitochondrial changes were assessed by measuring mitochondrial DNA content, morphology, membrane potential, cellular glucose uptake, ATP production and ROS generation. Nude mouse xenograft models were used to test anti-tumour effects of pentamidine in vivo. RESULTS: Pentamidine exerted profound inhibitory effects on proliferation, colony formation, migration and invasion of prostate cancer cells. In addition, the drug suppressed growth of xenograft tumours without exhibiting any obvious toxicity in nude mice. Mechanistically, pentamidine caused mitochondrial DNA content reduction and induced mitochondrial morphological changes, mitochondrial membrane potential dissipation, ATP level reduction, ROS production elevation and apoptosis in prostate cancer cells. CONCLUSIONS: Pentamidine can efficiently suppress prostate cancer progression and may serve as a novel mitochondria-targeted therapeutic agent for prostate cancer.

[Effects of an Amendment on Cadmium Transportation in the Rhizosphere Soil-Rice System].

The remediation of cadmium (Cd) contaminated paddy soils has become an important issue in the field of remediation of agricultural soils contaminated by heavy metals. The iron (Fe) redox cycle (referring to the fluctuation of iron between the ferrous (Ⅱ) and ferric (Ⅲ) oxidation states) exhibits a unique role in the transportation of Cd in the soil-rice system. The exploration of practical remediation strategies for Cd from the perspective of the Fe redox cycle is expected to obtain some state-of-the-art technologies and products to reduce Cd accumulation in rice grains. In this study, an amendment was selected and a field experiment was carried out to investigate the effects of this amendment on Cd transportation from the rhizosphere soil to the Fe plaque, and further to different rice tissues at four different growth stages, and to highlight some possible mechanisms by which the Fe redox cycle controls Cd availability in rice paddy fields. The results showed that the amendment induced the formation of Fe sulfides, which co-precipitated with Cd, reducing the NH4Ac-extractable Cd content in rhizosphere soils at the tillering, jointing, and filling stages; the oxidation of Fe sulfides increased the NH4Ac-extractable Cd content in the rhizosphere soil at the maturing stage; the formation of Fe sulfides in rhizosphere soils impeded the migration of Fe(Ⅱ) from the rhizosphere soil to the root surface, decreasing the content of DCB-extractable Fe and Cd in Fe plaques at the tillering and filling stages; the amendment inhibited Cd transportation from the roots to other tissues, increasing the proportion of Cd in the roots at the jointing, filling, and maturing stages, but decreasing the proportion in the straws at the jointing, filling, and maturing stages, and in the rice grain at the maturing stage. These findings provide a theoretical basis for the exploration and application of the amendment, and have significance in the field of remediation of Cd-contaminated paddy soils.

Splenic irradiation combined with tumor irradiation promotes T cell infiltration in the tumor microenvironment and helps in tumor control.

Locally applied radiation to the tumor is reported to stimulate systemic immune response. During radiotherapy to the abdominal cancer, spleen often receives certain dose, though as an important immune organ, little is known about the impact of splenic irradiation (SI) on systemic immune and local tumor control. Through a mice model, we found that the combination of SI with tumor irradiation (TI) helped in local control. The analysis of the tumor infiltrating leucocytes demonstrated that SI plus TI brought more T cell aggregation in the tumor microenvironment (TME), which helped in tumor control. Increased T cell infiltration may be partly due to higher expression of T cell chemokine in the TME and more expression of CXCR3 on the T cells in the spleen after SI. SI produced more IL-1ß in the spleen, IL-1ß stimulated the expression of CXCR3 on the T cells, and enhanced their migration ability. Taken together, radiation to the spleen combined with TI helped in local control through promoting T cell infiltration, and may be a considerable means to enhance the immunomodulatory of radiotherapy.

Mesenteric lymph drainage alleviates hemorrhagic shock-induced spleen injury and inflammation

Abstract Purpose: To investigate the effect of mesenteric lymph drainage on the spleen injury and the expressions of inflammatory cytokines in splenic tissue in mice following hemorrhagic shock. Methods: Male C57 mice were randomly divided into the sham shock, shock and shock+drainage groups. The mice in both shock and shock+drainage groups suffered femoral artery bleeding, maintained mean arterial pressure (MAP) of 40±2 mmHg for 90 min, and were resuscitated. And mesenteric lymph drainage was performed in the shock+drainage group at the time of resuscitation. After three hours of resuscitation, the splenic tissues were harvested for the histological observation and protein and mRNA expression analysis of cytokines. Results: The spleen in the shock group revealed a significantly structural damage and increased mRNA expressions of MyD88 and TRAF6 and protein expressions of TIPE2, MyD88, TRIF and TRAF3 compared to the sham group. By contrast, the splenic pathological injury in the shock+drainage group was alleviated significantly, and the mRNA and protein expressions of TIPE2, MyD88, TRIF, TRAF3 and TRAF6 were significantly lower than those in the shock group. Conclusion: These results indicate that post-hemorrhagic shock mesenteric lymph drainage alleviates hemorrhagic shock-induced spleen injury and the expressions of inflammatory cytokines.