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A 20-year-old female resident of Beijing intended to consume the eggs of the parasitic worm, Taenia saginata, for weight loss; however, she apparently inadvertently ingested Taenia solium (pork tapeworm) eggs, which resulted in disseminated cysticercosis. Cysticerci developed in the brain, tongue, muscles, liver, peritoneum, and subcutaneous tissues. She was administered oral albendazole and praziquantel. After four 10-day courses of treatment, most of the cysts disappeared and she recovered. After 3 years, the patient remains in good health.

Rice is one of the most important food crops in the world. Weeds seriously affect the rice yield and grain quality. In recent years, there are tremendous progresses in the research and application of herbicide-resistant genes in rice worldwide. This article reviews the working mechanisms of six herbicides (glyphosate, glufosinate, acetolactate synthase inhibitor herbicides, acetyl-CoA carboxylase inhibitor herbicides, hydroxyhenylpyruvate dioxygenase (HPPD) inhibitor herbicides and dinitroaniline herbicides), the resistance mutations of the corresponding herbicide-target genes, and the herbicide detoxification mechanisms by non-target genes. Examples are provided on herbicide-resistant rice materials obtained by transformation of exogenous resistance genes, by artificial mutagenesis and mutant screening, and by modifying the target genes through gene editing. This paper also introduces the current application of herbicide-resistant rice, points out problems that may be caused by utilization of herbicide resistant rice and solutions to the problems, and discusses the future prospects for the development of herbicide-resistant rice.

Graphene-based sponge is a novel hemostatic material prepared by chemical cross-link of graphene oxide. It has a fast fluid absorption capacity to quickly absorb blood from wounds, activate clotting pathways, and achieve rapid hemostasis. In addition, graphene-based sponge is also a good platform carrier. It can be prepared by organic cross-linking, compounding with inorganic clay, and adding bioactive factors to enhance coagulation stimulation. By these methods, the hemostatic performance of the sponge is further improved, which shows great potential for application in the field of trauma hemostasis. This article reviews the research progress of graphene-based sponges from three different preparation strategies (organic cross-linking, inorganic compounding and adding bioactive factor), summarizes their hemostatic mechanisms, and prospects the development of graphene-based hemostatic sponges.

Molecular self-assembly plays a very important role in various aspects of technology as well as in biological systems. Governed by covalent, hydrogen or van der Waals interactions–self-assembly of alike molecules results in a large variety of complex patterns even in two dimensions (2D). Prediction of pattern formation for 2D molecular networks is extremely important, though very challenging, and so far, relied on computationally involved approaches such as density functional theory, classical molecular dynamics, Monte Carlo, or machine learning. Such methods, however, do not guarantee that all possible patterns will be considered and often rely on intuition. Here, we introduce a much simpler, though rigorous, hierarchical geometric model founded on the mean-field theory of 2D polygonal tessellations to predict extended network patterns based on molecular-level information. Based on graph theory, this approach yields pattern classification and pattern prediction within well-defined ranges. When applied to existing experimental data, our model provides a different view of self-assembled molecular patterns, leading to interesting predictions on admissible patterns and potential additional phases. While developed for hydrogen-bonded systems, an extension to covalently bonded graphene-derived materials or 3D structures such as fullerenes is possible, significantly opening the range of potential future applications.

Obtaining a robust superconducting state in atomically precise nanographene (NG) structures by proximity to a superconductor could foster the discovery of topological superconductivity in graphene. On-surface synthesis of such NGs has been achieved on noble metals and metal oxides; however, it is still absent on superconductors. Here, we present a synthetic method to induce superconductivity of polymeric chains and NGs adsorbed on the superconducting Nb(110) substrate covered by thin Ag films. Using atomic force microscopy at low temperature, we characterize the chemical structure of each subproduct formed on the superconducting Ag layer. Scanning tunneling spectroscopy further allows us to elucidate the electronic properties of these nanostructures, which consistently show a superconducting gap.

Extracellular vesicles (EVs) are vehicles of intercellular communication that are released from various cell types under physiological and pathological conditions, with differing effects on the body. Under physiological conditions, EVs mediate cell-to-cell and intertissue communication and participate in maintaining homeostasis. Certain EV types have emerged as biological therapeutic agents in various fields, such as cell-free regenerative medicine, drug delivery and immunotherapy. However, the low yield of EVs is a bottleneck in the large-scale implementation of these therapies. Conversely, more EVs in the microenvironment in other circumstances, such as tumor metastasis, viral particle transmission, and the propagation of neurodegenerative disease, can exacerbate the situation, and the inhibition of EV secretion may delay the progression of these diseases. Therefore, the promotion and inhibition of EV release is a new and promising field because of its great research potential and wide application prospects. We first review the methods and therapeutic opportunities for the regulation of EV release based on the mechanism of EV biogenesis and consider the side effects and challenges.

TaMs1 encodes a non-specific lipid transfer protein (nsLTP) and is required for pollen development in wheat. Although MS1 is a Poaceae-specific gene, the roles of MS1 genes in other Poaceae plants are unknown, especially in rice and maize. Here, we identified one ortholog in rice (OsLTPg29) and two orthologs in maize (ZmLTPg11 and ZmLTPx2). Similar to TaMs1, both OsLTPg29 and ZmLTPg11 genes are specifically expressed in the microsporocytes, and both OsLTPg29 and ZmLTPg11 proteins showed lipid-binding ability to phosphatidic acid and several phosphoinositides. To determine their roles in pollen development, we created osltpg29 mutants and zmltpg11zmltpx2 double mutants by CRISPR/Cas9. osltpg29, not zmltpg11zmltpx2, is defective in pollen development, and only OsLTPg29, not ZmLTPg11, can rescue the male sterility of tams1 mutant. Our results demonstrate that the biological function of MS1 in pollen development differs in the evolution of Poaceae plants.

The breeding of herbicide-resistant wheat varieties has helped control weeds in wheat fields economically and effectively. Imidazolinone (IMI) herbicides are popular as they have low toxicity in mammals, are effective at small doses, and exhibit broad-spectrum herbicidal action in the field. Therefore, the isolation and genetic and molecular characterization of IMI-resistant wheat mutants will enhance weed management in wheat fields. In the present study, 352 IMI-resistant plants were isolated by genetic screening from a mutant pool prepared by EMS-based random mutagenesis. Cloning of the mutated genes from the IMI-resistant plants indicated that ten taals alleles had been isolated, and mutation in one of three TaALS homolog genes conferred IMI resistance, and such a mutation is a dominant trait. Further analysis showed that taals-d exhibited the greatest IMI resistance, whereas taals-b exhibited the weakest resistance to IMI among three homologous taals mutants. In terms of IMI resistance, the taals triple mutant was stronger than the taals double mutants, and the taals double mutants were stronger than the single mutants, indicating a dose-dependent effect of the TaALS mutation on IMI resistance in wheat. Biochemical analysis indicated that the mutation in TaALS increased the tolerance of TaALS to inhibition by IMI. Our work details the genetic and molecular characterization of als wheat mutants, provides a foundation for understanding IMI resistance and breeding wheat varieties with herbicide resistance, and indicates that genetic screening using a mutagenized pool is an effective and important means of breeding crops with additional desired agricultural traits.

Marine phycosphere hosts cross-kingdom algae-bacteria interactions playing a variety of crucial roles in aquatic ecosystems especially for the prevention and control of harmful algal blooms (HABs). During the investigation of structural composition of phycosphere microbiota (PM) of diverse marine HAB dinoflagellates, a Gram-negative, strictly aerobic, non-motile and rod-shaped bacterium designated LZ-17T was isolated from the phycosphere of highly toxic Alexandrium catenella LZT09. The 16S rRNA gene sequence analysis and the multilocus sequence analysis (MLSA) based on five protein-coding housekeeping genes (atpD, gyrB, mutL, topA and rpoD) indicated that strain LZ-17T was affiliated to the genus Maritimibacter within the family Rhodobacteraceae, and closely related to Maritimibacter alkaliphilus HTCC2654T (99.1%), ‘Maritimibacter harenae’ DP07T (97.9%) and M. lacisalsi X12M-4T (95.7%). The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain LZ-17T and the type strain of M. alkaliphilus were 96.9% and 74.7%. However, strain LZ-17T could be clearly distinguished from its closest by the phenotypical and phenotypical characteristics. Strain LZ-17T contained Q-10 as its major isoprenoid quinone, and summed feature 8 (C18:1 ω7c and/or C18:1 ω6c), C16:0 and C16:0 2-OH as the predominant fatty acids (>10%). The major polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol and phosphatidylcholine. The DNA G + C content was 64.3 mol%. Based on the polyphasic taxonomic characterization, strain LZ-17T represents a novel species of the genus Maritimibacter, for which the name Maritimibacter alexandrii sp. nov. is proposed, with the type strain LZ-17T (=CCTCC 2019005T = KCTC 72193T).

Heat stress has detrimental impacts on wheat growth and yield formation. Conferring heat tolerance through applying plant growth regulators is a feasible strategy to reduce loss. Gamma aminobutyric acid (GABA) is a four-carbon non-proteinogenic amino acid existing in organisms and accumulates in response to stress. In this study, spring wheat Liaochun17 and winter wheat Jingdu 40 were used to investigate the function of exogenous GABA on the heat tolerance of wheat seedlings. Data displayed that GABA treatment not only reduced the production of reactive active oxygen (ROS), but also improved the scavenging capacity of diphenyl picryl phenyl hydrazine active oxygen under heat stress, thus alleviating the accumulation of malondialdehyde and the damage of cell membrane. In addition, analysis of protein and amino acids revealed that GABA effectively promoted the accumulation of soluble protein and coordinated amino acid homeostasis. Summarily, our current findings revealed that GABA strengthened the resistance of wheat seedling to heat stress by maintaining the metabolism balance of ROS and amino acids.

MicroRNA-4458 (miR-4458) has been reported to be associated with several cancers including non-small-cell lung cancer (NSCLC), while its role in tumor immunity remains unclear. The purpose of the current research was to explore the anti-tumor immunity of miR-4458 in NSCLC. The results showed that the expression level of miR-4458 decreased and STAT3 increased in NSCLC tissues and cells. For in vitro experiments, miR-4458 mimics suppressed cell proliferation and decreased the expression level of PD-L1. Moreover, STAT3 was confirmed as a target gene of miR-4458. Upregulation of STAT3 level ameliorated the inhibitive effects of miR-4458 on cells proliferation and PD-L1 expression in cells. For in vivo studies, overexpression of miR-4458 hindered tumor growth, decreased the proportion of PD-1+ T cells, the expression of PD-L1 and IL-10, upregulated the proportion of CD4+ T, CD8+ T cells as well as the expression of IFN-γ and IL-2, which were all reversed by overexpression of STAT3, and the effects of STAT3 were counteracted after knockdown of PD-L1. MiR-4458 overexpression enhanced anti-tumor immunity via targeting STAT3 to block the PD-L1/PD-1 pathway.

Herbicide resistance in crop plants is valuable for integrated weed management in agriculture. Herbicide resistant rice, in particular, is important to management of weedy rice, a close relative of cultivated rice and a noxious weed prevalent in rice fields that remains challenging to farmers worldwide. Herbicide resistant plants can be obtained through transgenic approach or by mutagenesis of regular plant and screening of mutants with elevated resistance to herbicide. In this study, we conducted ethyl methyl sulfonate mutagenesis (EMS) to elite indica cultivar Huanghuazhan (HHZ) and screened for mutants resistant to imazapic, a herbicide that can inhibit the acetolactate synthase (ALS) in plants. We obtained three mutants of OsALS gene that have not been reported previously in rice. One of the mutants, with Trp548 changed to Met (W548M), was analyzed in more details in this study. This mutation had no negative effect on the plant physiology and morphology as well as rice yield. Compared with the imidazolinone-resistant mutant S627N (Ser627 changed to Asn) that has been deployed for Clearfield rice development, W548M mutant showed high levels of resistance to a broad spectrum of five families of ALS-inhibiting herbicides, in addition to a higher level of resistance to herbicides of the imidazolinone family. The herbicide-resistance was stably inherited by crossing into other rice lines. Thus, the W548M mutation provides a valuable resource for breeding of herbicide resistant rice and weed management.

Anti-lipopolysaccharide factors (ALFs) exhibit a potent antimicrobial activity against a broad range of bacteria, filamentous fungi, and viruses. In previous reports, seven groups of ALFs (groups A–G) were identified in penaeid shrimp. Among them, group D showed negative net charges and weak antimicrobial activity. Whether this group has antiviral function is not clear. In this study, the ALF sequences of penaeid shrimp were analyzed, and eight groups of ALF family (groups A–H) were identified. The four ALFs including MjALF-C2, MjALF-D1, MjALF-D2, and MjALF-E2 from kuruma shrimp Marsupenaeus japonicus were expressed recombinantly in Escherichia coli, and the antiviral activity was screened via injection of purified recombinant ALFs into shrimp following white spot syndrome virus (WSSV) infection. Results showed that the expression of Vp28 (WSSV envelope protein) decreased significantly in the MjALF-D2-injected shrimp only. Therefore, MjALF-D2 was chosen for further study. Expression pattern analysis showed that MjAlf-D2 was upregulated in shrimp challenged by WSSV. The WSSV replication was detected in RNA, genomic DNA, and protein levels using VP28 and Ie1 (immediate-early gene of WSSV) as indicators in MjALF-D2-injected shrimp following WSSV infection. Results showed that WSSV replication was significantly inhibited compared with that in the rTRX- or PBS-injected control groups. After knockdown of MjAlf-D2 in shrimp by RNA interference, the WSSV replication increased significantly in the shrimp. All these results suggested that MjALF-D2 has an antiviral function in shrimp immunity, and the recombinant ALF-D2 has a potential application for viral disease control in shrimp aquaculture.

The breeding and large-scale application of hybrid rice contribute significantly to the food supply worldwide. Currently, hybrid seed production uses cytoplasmic male sterile (CMS) lines or photoperiod/thermo-sensitive genic male sterile (PTGMS) lines as female parent. Despite huge successes, both systems have intrinsic problems. CMS systems are mainly restricted by the narrow restorer resources that make it difficult to breed superior hybrids, while PTGMS systems are limited by conditional sterility of the male sterile lines that makes the propagation of both PTGMS seeds and hybrid seeds vulnerable to unpredictable climate changes. Recessive nuclear male sterile (NMS) lines insensitive to environmental conditions are widely distributed and are ideal for hybrid rice breeding and production, but the lack of effective ways to propagate the pure NMS lines in a large scale renders it impossible to use them for hybrid rice production. The development of “the third-generation hybrid rice technology” enables efficient propagation of the pure NMS lines in commercial scale. This paper discusses the establishment of “the third-generation hybrid rice technology” and further innovations. This new technology breaks the limitations of CMS and PTGMS systems and will bring a big leap forward in hybrid rice production.

Fish contain many important nutrients and are primarily known for high n-3 polyunsaturated fatty acids (n-3 PUFA) content. Studies have shown that supplementation of fish oil-derived n-3 PUFA improves muscle mass and strength. Here, we hypothesized that fish consumption might improve muscle strength. To test this hypothesis, we performed this cross-sectional study (n = 29,084) in Tianjin, China. The frequency of fish consumption was assessed using a valid self-administered food frequency questionnaire. Handgrip strength (HGS) was used as the indicator of muscle strength, and was measured using a handheld digital dynamometer. Analysis of covariance was used to examine the relationship between fish consumption and HGS. In men, after adjusted potential confounding factors, the least square means (95% confidence intervals) of HGS across saltwater fish consumption categories were 41.5 (41.1, 43.7) kg for1 time/week, 44.6 (43.2, 45.8) kg for 1 time/week, and 44.7 (43.3, 46.1) kg for ≥2 to 3 times/week (P for trend0.001). In men, the least square means (95% confidence intervals) of HGS across the ascending quartiles of dietary n-3 PUFA intake were 43.6 (43.2, 44.4) kg, 43.7 (43.2, 44.6) kg, 44.4 (43.0, 45.8) kg, and 44.6 (43.1, 46.0) kg (P for trend0.01). The results showed that saltwater fish consumption was positively related to HGS in men, but not in women, suggesting that saltwater fish contain nutrients that may be used to improve HGS.

Aims: Acinetobacter baumannii is notorious for acquiring antibiotic resistance and causing nosocomial infections worldwide. This study aimed to investigate the prevalence and molecular characterist...

Quorum sensing gene expression in vibrios is regulated by the LuxR/HapR family of transcriptional factors, which includes Vibrio vulnificus SmcR. The consensus binding site of Vibrio LuxR/HapR/SmcR proteins is palindromic but highly degenerate with sequence variations at each promoter. To examine the mechanism by which SmcR recognizes diverse DNA sites, we generated SmcR separation-of-function mutants that either repress or activate transcription but not both. SmcR N55I is restricted in recognition of single base-pair variations in DNA binding site sequences and thus is defective at transcription activation but retains interaction with RNA polymerase (RNAP) alpha. SmcR S76A, L139R and N142D substitutions disrupt the interaction with RNAP alpha but retain functional DNA binding activity. X-ray crystallography and small angle X-ray scattering data show that the SmcR DNA binding domain exists in two conformations (wide and narrow), and the protein complex forms a mixture of dimers and tetramers in solution. The three RNAP interaction-deficient variants also have two DNA binding domain conformations, whereas SmcR N55I exhibits only the wide conformation. These data support a model in which two mechanisms drive SmcR transcriptional activation: interaction with RNAP and a multi-conformational DNA binding domain that permits recognition of variable DNA sites.

Osteoporosis is one of the most common metabolic bone diseases affecting millions of people. We previously found that harmine prevents bone loss in ovariectomized mice via increasing preosteoclast platelet‐derived growth factor‐BB (PDGF‐BB) production and type H vessel formation. However, the molecular mechanisms by which harmine promotes preosteoclast PDGF‐BB generation are still unclear. In this study, we revealed that inhibitor of DNA binding‐2 (Id2) and activator protein‐1 (AP‐1) were important factors implicated in harmine‐enhanced preosteoclast PDGF‐BB production. Exposure of RANKL‐induced Primary bone marrow macrophages (BMMs), isolated from tibiae and femora of mice, to harmine increased the protein levels of Id2 and AP‐1. Knockdown of Id2 by Id2‐siRNA reduced the number of preosteoclasts as well as secretion of PDGF‐BB in RANKL‐stimulated BMMs administrated with harmine. Inhibition of c‐Fos or c‐Jun (components of AP‐1) both reversed the stimulatory effect of harmine on preosteoclast PDGF‐BB production. Dual‐luciferase reporter assay analyses determined that PDGF‐BB was the direct target of AP‐1 which was up‐regulated by harmine treatment. In conclusion, our data demonstrated a novel mechanism involving in the production of PDGF‐BB increased by harmine, which may provide potential therapeutic targets for bone loss diseases.

Multifunctional entities have recently been attractive for the development of anticancer chemotherapeutic drugs. However, such entities with concurrent CK2 along with cancer stem cell (CSC) inhibitory activities are rare in a single small molecule. Herein, a series of 5-(3-chlorophenylamino)benzo[c][2,6]naphthyridine derivatives were synthesized using a known CK2 inhibitor, silmitasertib (CX-4945), as the lead compound. Among the resulting compounds, 1c exhibited stronger CK2 inhibitory activity with higher Clk2/CK2 selectivity than CX-4945. Significantly, 1c could modulate the Akt1(ser129)-GSK-3β(ser9)-Wnt/β-catenin signaling pathway and inhibit the expression of the stemness marker ALDH1A1, CSC surface antigens, and stem genes, showing potent CSC inhibitory activity. Moreover, 1c also displayed superior pharmacokinetics and antitumor activity compared with CX-4945 sodium salt, without obvious toxicity. The favorable antiproliferative and antitumor activity of 1c, its high inhibitory selectivity for CK2, and its potent inhibition of cancer cell stemness make this molecule a candidate for the treatment of cancer.

Bruton tyrosine kinase (BTK) inhibitor ibrutinib has been validated as an effective drug to treat B cell malignancies. Combined therapies comprising ibrutinib and anti-CD20 antibodies like rituximab were designed as a backbone in many clinical trials. However, the off-target inhibition of ibrutinib on interleukin-2 (IL-2)-inducible T cell kinase (ITK) may reduce rituximab’s antibody-dependent cellular cytotoxicity (ADCC) efficacy. Orelabrutinib (Orel), a novel BTK inhibitor, was designed with high selectivity to BTK. In our study, we demonstrated in preclinical models that orelabrutinib in combination with rituximab could preserve NK-cell-mediated ADCC induced by rituximab and enhanced the apoptosis of tumor cells in vitro. The addition of orelabrutinib to rituximab had produced promising combined anti-tumor effects in B cell lymphomas in vivo. Collectively, combination therapy of orelabrutinib with rituximab would benefit patients with B cell lymphoma, especially those with relapsed or refractory disease., Graphical abstract, The highly selective BTK inhibitor orelabrutinib has no significant effect on IL-2-inducible T cell kinase, which preserved the ADCC effects of rituximab induced by NK cells. The combination of orelabrutinib and rituximab will likely benefit patients with B cell malignant tumors, especially those with relapsed or refractory disease.

Zhong-Wei Luo,1,2 Kun Xia,1,2 Yi-Wei Liu,1,2 Jiang-Hua Liu,1,2 Shan-Shan Rao,2,3 Xiong-Ke Hu,1,2 Chun-Yuan Chen,1,2 Ran Xu,4 Zhen-Xing Wang,1,2 Hui Xie1,2,5– 8 1Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Xiangya Nursing School, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 5Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 6Hunan Key Laboratory of Organ Injury, Aging and Regenerative Medicine, Changsha, Hunan, People’s Republic of China; 7Hunan Key Laboratory of Bone Joint Degeneration and Injury, Changsha, Hunan, People’s Republic of China; 8National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Hui XieDepartment of Orthopedics, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People’s Republic of ChinaEmail huixie@csu.edu.cnRan XuDepartment of Urology, The Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan, 410011, People’s Republic of ChinaEmail xuran@csu.edu.cnPurpose: Prostate cancer (PCa) is one of the most common malignancies in males. Despite the success of immunotherapy in many malignant cancers, strategies are still needed to improve therapeutic efficacy in PCa. This study aimed to investigate the effects of Akkermansia muciniphila-derived extracellular vesicles (Akk-EVs) on PCa and elucidate the underlying immune-related mechanism.Methods: Akk-EVs were isolated by ultracentrifugation and intravenously injected to treat syngeneic PCa-bearing immune-competent mice. Immunophenotypic changes in immune cells, such as cytotoxic T lymphocytes and macrophages, were measured via flow cytometry analysis. Histological examination was used to detect morphological changes in major organs after Akk-EVs treatments. In vitro, flow cytometry was performed to confirm the effects of Akk-EVs on the activation of CD8+ T cells. Quantitative PCR and immunofluorescence staining were carried out to test the impact of Akk-EVs on macrophage polarization. Cell counting kit-8 (CCK-8) analysis, colony formation assays, and scratch wound healing assays were conducted to assess the effects of Akk-EVs-treated macrophages on the proliferation and invasion of PCa cells. CCK-8 assays also confirmed the impact of Akk-EVs on the viability of normal cells.Results: Intravenous injection of Akk-EVs in immune-competent mice reduced the tumor burden of PCa without inducing obvious toxicity in normal tissues. This treatment elevated the proportion of granzyme B-positive (GZMB+) and interferon γ-positive (IFN-γ+) lymphocytes in CD8+ T cells and caused macrophage recruitment, with increased tumor-killing M1 macrophages and decreased immunosuppressive M2 macrophages. In vitro, Akk-EVs increased the number of GZMB+CD8+ and IFN-γ+CD8+ T cells and M1-like macrophages. In addition, conditioned medium from Akk-EVs-treated macrophages suppressed the proliferation and invasion of prostate cells. Furthermore, the effective dose of Akk-EVs was well-tolerated in normal cells.Conclusion: Our study revealed the promising prospects of Akk-EVs as an efficient and biocompatible immunotherapeutic agent for PCa treatment.Keywords: Akkermansia muciniphila, extracellular vesicles, immunotherapy, prostate cancer, cytotoxic T lymphocytes, macrophages

In this work, the one-step stereochemical antimicrobial finishing of cotton textiles (CT) was achieved by the oxidative copolymerization of a dopamine-menthol derivative (DAM) and dopamine (DA). The obtained DAM-modified CT (P(DAM-co-DA)-CT) exhibited broad-spectrum microbial anti-adhesion properties against bacteria (E. coli and P. aeruginosa), including superbugs (MRSA and VREF), and fungi (A. niger, A. flavus, M. racemosus and P. chrysogenum). Because of its unique stereochemical antimicrobial mechanism, the obtained P(DAM-co-DA)-CT is a non-releasing antimicrobial material that causes no skin sensitization and exhibits good biocompatibility. The coating was also found to enhance the UV-resistant and mechanical properties of the CT. Furthermore, it displayed durable washing fastness and antimicrobial properties after the endurance of 30 laundering cycles. The observed achievements provide a broader understanding of stereochemical antimicrobial surfaces and endow this method with wider applications.

The insect cuticle is a multifunctional shield providing shape stabilization and threat protection. It has a complex composition of cuticular components. Although cuticular melanization is essential and melanin spots are common for many insects, information about the connection between melanization and other cuticular components is limited. The ladybird Harmonia axyridis adults and pupae exhibit regular and predictable melanin spots on their cuticles. Here, RNAi-mediated silencing of CYP4G79 , which functions as an oxidative decarbonylase in hydrocarbon biosynthesis, decreased the cuticular hydrocarbon contents at different levels of H. axyridis , resulted in enlarging (mild) or breaking (severe) melanin spots on cuticle. In addition, transcriptional analysis showed key genes of cuticular melanization up-regulated under CYP4G79 RNAi; Scanning electron microscope (SEM) and Oil Red O (ORO)-staining results suggested a distribution correlation among Cuticular hydrocarbons (CHCs), lipids and melanin. For severe phenotypes with broken melanin spots of treated beetle’s pupal cuticle, histological examinations showed that abnormal pigmentation in cuticular layers were physiologically caused by cuticular microstructural change. In brief, these two cuticular components of H. axyridis , may function together; and cuticular hydrocarbons are essential to the formation of melanin spots. Furthermore, the orderly formations of cuticular components are important to cuticle construction; this study furthers our understanding of insect cuticle formation and functions.

The stress‐dominance hypothesis (SDH) predicts that environmental filtering will dominate in harsh habitats, while limiting similarity is more important in favourable environments. Here, we test the generality of the SDH to disentangle the relative importance of these two ecological processes along a sand desertification gradient. Data were collected from randomly selected locations in a desert steppe community in Northwest China. In this region, intense habitat fragmentation has resulted in a series of original soil habitat patches called soil islands. These soil islands typically contain Sierozem soils historically subjected to low (L), medium (M), and high (H) levels of sand desertification. Along this sand desertification gradient, soil properties and leaf traits (LDMC, leaf dry matter content; SLA, specific leaf area; LC, leaf carbon concentration; LP, leaf phosphorus concentration; and LN, leaf nitrogen concentration) were measured. We then tested for trait and phylogenetic convergence or divergence using a null model approach. Along the sand desertification gradient, trait convergence trend decreased, while trait divergence trend increased. Similarly, the phylogenetic convergence trends decreased. Traits displaying convergence included LDMC, SLA, and LCC, while LP and LN displayed divergence. The strength of LDMC convergence was negatively correlated with community weighted mean trait values (CWM) for LDMC. In contrast, the strength of LN divergence was positively correlated with CWM for LN. Our results pertaining to LDMC and LN support the SDH. Along the sand desertification gradient, the strength of environmental filtering gradually decreased, while the intensity of limiting similarity gradually increased.

It is known that the tailings of gold mines have brought serious heavy metal pollution; however, the heavy metal pollution caused by gold tailings in specific geological environments and extraction processes still must be studied. This study investigated the distribution, speciation, bioaccumulation, and pollution of heavy metals in soils from the Yueliangbao gold tailings area in central China, where gold was extracted by cyanidation. The results show that the concentrations of Cu, Pb, Zn, Mn, Mo, and Cd in the soils of the tailings pond were higher than those in the local background. The concentrations of heavy metals related to mineralization activities, such as Cu, Pb, Zn, and Mo, varied with the distance to the tailings pond center. There was a decreasing trend of tailings pond center > tailings pond entrance > surrounding environment. This study’s gold tailings pond differed from those of other regions because of its high content of unextracted Cu remaining in the pond. The proportion of non-residual Cu in the tailing pond soil was much higher than that of residual Cu, indicating it was likely to migrate to the surrounding environment. The pollution assessment indicated that the tailings pond soils were heavily polluted by Cu, and the level of heavy metal pollution in soils was positively correlated with the distance to the tailings pond center. Consequently, this tailings pond may become a source of Cu pollution in the surrounding environment, thus endangering environmental safety and human health. The study of heavy metal concentrations in the dominant plants showed that Chinese brake (Pteris vittata L.), Ramose scouring rush (Equisetum ramosissimum), and Manyflower silvergrass (Miscanthus floridulus) had the potential to be used for the phytostabilization of Cu.

During characterization of rhizobacteria, strain DBTS2T was isolated from the rhizosphere soil samples of healthy tomato plants and characterized using a polyphasic taxonomic approach. Phylogenetic analysis using 16S rRNA gene sequences showed this strain belonged to the genus Rhizobium and was most closely related to Rhizobium subbaraonis JC85T (99.1%) and Rhizobium daejeonense CCBAU 10050T (97%). Cells of strain DBTS2T were Gram-negative, short rod, aerobic and non-motile. This novel strain was found to grow at 20–45 °C (optimum 25–37 °C), pH 5–9 (optimum 8) and in the presence of 4% NaCl. It was positive for catalase and oxidase. The predominant cellular fatty acids were Summed Feature 8 (52.7%) and C19:0 cyclo ω8c (23.3%). The polar lipids of strain DBTS2T consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, unidentified aminophospholipid, unidentified aminolipid, four unidentified phospholipids, unidentified lipid, phosphatidylcholine, unknown glycolipid and unknown aminophosphoglycolipids. Q-10 was the major quinone. The DNA–DNA hybridization similarity values between the strain DBTS2T and R. subbaraonis JC85T, R. daejeonense CCBAU 10050T and Rhizobium azooxidifex DSM100211T were 46.4%, 20.7% and 25.5%, respectively. The ANI value was 91.96% between strain DBTS2T and R. subbaraonis JC85T and 75.18% between strain DBTS2T and R. daejeonense CCBAU 10050T. The DNA G+C content of the genomic DNA was 63.1 mol%. Based on these results, it was concluded that the isolate represents a novel species of the genus Rhizobium, for which the name Rhizobium rhizolycopersici sp. nov. is proposed, with DBTS2T (= CICC 24887T = ACCC61707 = JCM 34245) as the type strain.

Drug resistance and tumor recurrence are major challenges in cancer treatment. Cancer cells often display centrosome amplification. To maintain survival, cancer cells achieve bipolar division by clustering supernumerary centrosomes. Targeting centrosome clustering is therefore considered a promising therapeutic strategy. However, the regulatory mechanisms of centrosome clustering remain unclear. Here we report that KIFC1, a centrosome clustering regulator, is positively associated with tumor recurrence. Under DNA damaging treatments, the ATM and ATR kinases phosphorylate KIFC1 at Ser26 to selectively maintain the survival of cancer cells with amplified centrosomes via centrosome clustering, leading to drug resistance and tumor recurrence. Inhibition of KIFC1 phosphorylation represses centrosome clustering and tumor recurrence. This study identified KIFC1 as a prognostic tumor recurrence marker, and revealed that tumors can acquire therapeutic resistance and recurrence via triggering centrosome clustering under DNA damage stresses, suggesting that blocking KIFC1 phosphorylation may open a new vista for cancer therapy., Centrosome clustering is a promising therapeutic target in cancer but how it is regulated remains unclear. Here, the authors show that in response to DNA damage, ATM/ATR stabilize the centrosome clustering regulator KIFC1 leading to increased clustering efficiency and tumour recurrence.

Gestational diabetes mellitus (GDM) has become a global health concern as the main result of its contribution to the high risk of adverse pregnancy outcomes for both the mother and fetus. However, there is absence of an ideal and widely acceptable therapy. Nuciferine has previously been shown to exert beneficial effects in various metabolic diseases. This study aimed to investigate the potential therapeutic efficacy of nuciferine on GDM in C57BL/6J mice induced by a high-fat diet (HFD), which has not been reported before. The results showed that nuciferine improved glucose intolerance, reduced lipid accumulation and increased the glycogen content within hepatocytes, and decreased placental lipid and glycogen deposition, thus ameliorating glycolipid disorders in GDM mice. Additionally, nuciferine protected against histological degeneration of metabolism-associated critical organs including the liver, pancreas, and abdominal adipose tissue. Most interestingly, nuciferine could correct intestinal dysbacteriosis in GDM mice, as evidenced by the elevation of probiotic abundances consisting of Akkermansia, Lactobacillus, and Bifidobacterium, which were all negatively correlated with serum and liver triglyceride (TG) and positively associated with hepatic glycogen, and the reduction of conditional pathogen abundances including Escherichia-Shigella and Staphylococcus, and the latter was positively related to serum and liver TG and negatively linked with liver glycogen. Collectively, these findings suggest that nuciferine as a food-borne strategy played important roles in the management of GDM.

Insect resistance to insecticides is an increasingly serious problem, and the resistant mechanisms are complicated. The resistance research based on the chemosensory pathway is one of the hot problems at present, but the specific binding mechanism of chemosensory genes and insecticides remains elusive. The binding mechanism of AlepGOBP2 (belong to insect chemosensory gene) with two insecticides was investigated by computational and experimental approaches. Our calculation results indicated that four key residues (Phe12, Ile52, Ile94, and Phe118) could steadily interact with these two insecticides and be assigned as hotspot sites responsible for their binding affinities. The significant alkyl-π and hydrophobic interactions involved by these four hotspot residues were found to be the driving forces for their binding affinities, especially for two residues (Phe12 and Ile94) that significantly contribute to the binding of chlorpyrifos, which were also validated by our binding assay results. Furthermore, we also found that the AlepGOBP2-chlorpyrifos/phoxim complexes can be more efficiently converged in the residue-specific force field-(RSFF2C) and its higher accuracy and repeatability in protein dynamics simulation, per-residue free energy decomposition, and computational alanine scanning calculations have also been achieved in this paper. These findings provided useful insights for efficient and reliable calculation of the binding mechanism of relevant AlepGOBPs with other insecticides, facilitating to develop new and efficient insecticides targeting the key sites of AlepGOBP2.

T‐cell exhaustion is one of the hallmarks in cancer, but the mechanisms underlying T‐cell dysregulation remains unclear. Here, we reported that down‐regulation of transcription factor EOMES contributed to increased levels of inhibitory receptors in T cell among the tumour tissues and resulted in the poor prognosis of hepatocellular carcinoma (HCC). By analysing the correlation between EOMES in tumour‐infiltrating T cells and the clinical features, we demonstrated that the EOMES was related to the advanced stage and poor prognosis of HCC. Further mechanistic studies revealed that the EOMES mainly expressed in the CD8+ T cells and were down‐regulated in tumour samples. Moreover, we demonstrated that the EOMES directly bound at the transcriptional regulatory regions of the key inhibitory factors including PD‐1, CTAL‐4 and CD39, and lower levels of EOMES contributed to overexpression of these factors in T cells. Together, our studies provide new insight into the transcriptional deregulation of the inhibitory receptors on T cells during the tumorigenesis.

Poly (ADP-ribose) polymerase (PARP) plays a significant role in DNA repair responses; therefore, this enzyme is targeted by PARP inhibitors in cancer therapy. Here we have developed a number of fused tetra- or pentacyclic dihydrodiazepinoindolone derivatives with excellent PARP enzymatic and cellular PARylation inhibition activities. These efforts led to the identification of pamiparib (BGB-290, 139), which displays excellent PARP-1 and PARP-2 inhibition with IC50 of 1.3 and 0.9 nM, respectively. In a cellular PARylation assay, this compound inhibits PARP activity with IC50 = 0.2 nM. Cocrystal of pamiparib shows similar binding sites with PARP with other PARP inhibitors, but pamiparib is not a P-gp substrate and shows excellent drug metabolism and pharmacokinetics (DMPK) properties with significant brain penetration (17-19%, mice). The compound is currently being investigated in phase III clinical trials as a maintenance therapy in platinum-sensitive ovarian cancer and gastric cancer.

Enterobacter sp. A11 and Comamonas sp. A23 were isolated and identified. Coculturing these two strains with Cd(II) led to the production of biofilm, H2S, and succinic acid (SA), and Cd(II) was adsorbed by cells and formed CdS precipitates. After centrifugation, 97% Cd(II) was removed from the coculture. Proteomic and metabolomic analyses of the cocultured bacteria revealed that H2S and SA production pathways, metal transportation, and TCA cycle were active under Cd(II) stress. In vitro addition of SA enhanced the production of H2S and biofilm formation and Cd(II) adsorption. Two-season greenhouse pot experiments with Brassica rapa L. were performed with and without the coculture bacteria. Compared with the control, the average Cd amounts of the two-season pot experiments of the aboveground plants were decreased by 71.3%, 62.8%, and 38.6%, and the nonbioavailable and immobilized Cd in the soils were increased by 211.8%, 213.4%, and 116.7%, for low-, medium-, and high- Cd-spiked soils, respectively. The two strains survived well in soil during plant growth using plate counting, quantitative real-time PCR, and metagenomics analysis. Our results indicate that the combination of Enterobacter and Comamonas strains with the production of H2S and biofilm are important effectors for the highly efficient immobilization of Cd.

Senile osteoporosis (OP) is often concomitant with decreased autophagic activity. OPTN (optineurin), a macroautophagy/autophagy (hereinafter referred to as autophagy) receptor, is found to play a pivotal role in selective autophagy, coupling autophagy with bone metabolism. However, its role in osteogenesis is still mysterious. Herein, we identified Optn as a critical molecule of cell fate decision for bone marrow mesenchymal stem cells (MSCs), whose expression decreased in aged mice. Aged mice revealed osteoporotic bone loss, elevated senescence of MSCs, decreased osteogenesis, and enhanced adipogenesis, as well as optn(–)(/ –) mice. Importantly, restoring Optn by transplanting wild-type MSCs to optn(–)(/ –) mice or infecting optn(–)(/ –) mice with Optn-containing lentivirus rescued bone loss. The introduction of a loss-of-function mutant of Optn(K193R) failed to reestablish a bone-fat balance. We further identified FABP3 (fatty acid binding protein 3, muscle and heart) as a novel selective autophagy substrate of OPTN. FABP3 promoted adipogenesis and inhibited osteogenesis of MSCs. Knockdown of FABP3 alleviated bone loss in optn(–)(/ –) mice and aged mice. Our study revealed that reduced OPTN expression during aging might lead to OP due to a lack of FABP3 degradation via selective autophagy. FABP3 accumulation impaired osteogenesis of MSCs, leading to the occurrence of OP. Thus, reactivating OPTN or inhibiting FABP3 would open a new avenue to treat senile OP. Abbreviations: ADIPOQ: adiponectin, C1Q and collagen domain containing; ALPL: alkaline phosphatase, liver/bone/kidney; BGLAP/OC/osteocalcin: bone gamma carboxyglutamate protein; BFR/BS: bone formation rate/bone surface; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CDKN1A/p21: cyclin-dependent kinase inhibitor 1A; CDKN2A/p16: cyclin dependent kinase inhibitor 2A; CDKN2B/p15: cyclin dependent kinase inhibitor 2B; CEBPA: CCAAT/enhancer binding protein (C/EBP), alpha; COL1A1: collagen, type I, alpha 1; Ct. BV/TV: cortical bone volume fraction; Ct. Th: cortical thickness; Es. Pm: endocortical perimeter; FABP4/Ap2: fatty acid binding protein 4, adipocyte; H2AX: H2A.X variant histone; HE: hematoxylin and eosin; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MAR: mineral apposition rate; MSCs: bone marrow mesenchymal stem cells; NBR1: NBR1, autophagy cargo receptor; OP: osteoporosis; OPTN: optineurin; PDB: Paget disease of bone; PPARG: peroxisome proliferator activated receptor gamma; Ps. Pm: periosteal perimeter; qRT-PCR: quantitative real-time PCR; γH2AX: Phosphorylation of the Serine residue of H2AX; ROS: reactive oxygen species; RUNX2: runt related transcription factor 2; SA-GLB1: senescence-associated (SA)-GLB1 (galactosidase, beta 1); SP7/Osx/Osterix: Sp7 transcription factor 7; SQSTM1/p62: sequestosome 1; TAX1BP1: Tax1 (human T cell leukemia virus type I) binding protein 1; Tb. BV/TV: trabecular bone volume fraction; Tb. N: trabecular number; Tb. Sp: trabecular separation; Tb. Th: trabecular thickness; μCT: micro computed tomography.

Phenotypic plasticity is observed in many animal species and it is effective for them to cope with many types of environmental threats. The multicolored Asian ladybird Harmonia axyridis shows a cuticular pigmentation plasticity that can be rapidly induced by temperature changes, and in the form of changeable melanin spot patterns to adjust heat-absorbing. Here, H. axyridis with thermal stimulation were selected for determining the molecular regulations behind it. First, we confirmed the melanin level changes of H. axyridis pupa could be induced by temperature, and then screened the efficient time window for thermal sensing of H. axyridis pre-pupa; it is suggested that the late stage of pre-pupa (late stage of 4th instar larva) is the critical period to sense thermal signals and adjust its pupal melanin spot area size to adapt to upcoming thermal conditions. The Ha-ADC (aspartate decarboxylase) and Ha-ebony (NBAD synthase) of aspartate-β-alanine-NBAD pathway were then proved in regulation of cuticular melanization for pupa through RNA interference experiments; knockdown of these two genes enlarged the melanin spot size. Finally, we designed a random injection of Ha-ADC at different pre-pupal stages, to further study the regulation window during this process. Combined with all evidence observed, we suggested the spot size determination can be regulated very close to the time point of pupation, and genes of the aspartate-β-alanine-NBAD pathway play an important role at the molecular level. In brief, H. axyridis exhibits a flexible active physiological regulation through transcriptional modification to thermal changes.

Aim Renal injury induced by diabetes is reported to be associated with inflammation. Isomangiferin (ISO), a xanthone C-glucoside from the Cyclopia subfamily, exhibits many pharmacological properties. This study aimed to evaluate the protection of ISO against renal damage in diabetic mice. Methods Serum glucose, insulin, uric acid, creatinine, total cholesterol (TC), triglyceride (TG), and inflammatory cytokines in serum and the kidney of db/db diabetes model mice were detected. The components of high mobility group protein B1 (HMGB1)/NACHT leucine-rich repeat- and PYD-containing 3 (NLRP3)/nuclear factor kappa-B (NF-κB) pathway in the kidney were detected by Western blot and immunohistochemical analysis. Results ISO improved lipid profile and glucose tolerance, and inhibited the production of inflammatory cytokines in a db/db model mice. Moreover, ISO decreased biochemical indexes in the serum and inhibited the activation of HMGB1/NLRP3/NF-κB signaling in the kidney of db/db model mice. Conclusion ISO provides protection against renal injury via inhibiting HMGB1/NLRP3/NF-κB signaling in a diabetic mouse model.

CD83, either in its membrance-bound form (mCD83) or soluble form (sCD83), is an important immunomodulatory molecule in humans and mice. While mCD83 is immunostimulatory, sCD83 exhibits striking immunosuppressive activities, suggesting that sCD83 may be used to combat inflammatory diseases, such as rheumatoid arthritis, graft-versus-host disease and habitual abortion. Although many studies had shed lights on the role of CD83 in humans and mice, little is known about CD83 in other animals. Recently, we showed that porcine CD83 had similar biochemical characteristics and immunoregulatory functions as its human counterpart. However, whether porcine sCD83 (psCD83) is involved in maintaining the immunological tolerance at the maternal-fetal interface and thereby prevents embryo loss and abortion during pregnancy is unclear. In this study, we used LPS-induced animal model to analyze the effect of porcine sCD83 on the mouse abortion. Results showed that psCD83 could significantly alleviate LPS-induced abortion in mice, indicating that the psCD83 had the function of fetal protection. Mechanically, psCD83-mediated fetal protection was related to the promotion on Th2 cytokine production, Treg cell differentiation and trophoblast invasion. This study provides a molecular basis for the fetal protection of psCD83, as well as a potential target for the regulation of maternal-fetal interfacial immune tolerance.

Touch can positively influence cognition and emotion, but the underlying mechanisms remain unclear. Here, we report that tactile experience enrichment improves memory and alleviates anxiety by remodeling neurons along the dorsoventral axis of the dentate gyrus (DG) in adult mice. Tactile enrichment induces differential activation and structural modification of neurons in the dorsal and ventral DG, and increases the presynaptic input from the lateral entorhinal cortex (LEC), which is reciprocally connected with the primary somatosensory cortex (S1), to tactile experience-activated DG neurons. Chemogenetic activation of tactile experience-tagged dorsal and ventral DG neurons enhances memory and reduces anxiety respectively, whereas inactivation of these neurons or S1-innervated LEC neurons abolishes the beneficial effects of tactile enrichment. Moreover, adulthood tactile enrichment attenuates early-life stress-induced memory deficits and anxiety-related behavior. Our findings demonstrate that enriched tactile experience retunes the pathway from S1 to DG and enhances DG neuronal plasticity to modulate cognition and emotion., Touch can positively modulate cognitive performance and emotional response. Here the authors demonstrate that enriched tactile experience improves memory and reduces anxiety in adult mice by remodelling the pathway from the primary somatosensory cortex to the dentate gyrus.

Following germination in the dark, Arabidopsis (Arabidopsis thaliana) seedlings undergo etiolation and develop apical hooks, closed cotyledons, and rapidly elongating hypocotyls. Upon light perception, the seedlings de-etiolate, which includes the opening of apical hooks and cotyledons. Here, we identify Arabidopsis Small Auxin Up RNA17 (SAUR17) as a downstream effector of etiolation, which serves to bring about apical hook formation and closed cotyledons. SAUR17 is highly expressed in apical hooks and cotyledons and is repressed by light. The apical organs also express a group of light-inducing SAURs, as represented by SAUR50, which promote hook and cotyledon opening. The development of etiolated or de-etiolated apical structures requires asymmetric differential cell growth. We present evidence that the opposing actions of SAUR17 and SAUR50 on apical development largely result from their antagonistic regulation of Protein Phosphatase 2C D-clade 1 (PP2C-D1), a phosphatase that suppresses cell expansion and promotes apical hook development in the dark. SAUR50 inhibits PP2C-D1, whereas SAUR17 has a higher affinity for PP2C-D1 without inhibiting its activity. PP2C-D1 predominantly associates with SAUR17 in etiolated seedlings, which shields it from inhibitory SAURs such as SAUR50. Light signals turn off SAUR17 and upregulate a subgroup of SAURs including SAUR50 at the inner side of the hook and cotyledon cells, leading to cell expansion and unfolding of the hook and cotyledons.

Gastric cancer is a common malignancy worldwide. The occurrence of multidrug resistance (MDR) is the major obstacle for effective gastric cancer chemotherapy. In this study, the in-depth molecular mechanism of the DJ-1-induced MDR in SGC7901 gastric cancer cells was investigated. The results showed that DJ-1 expression level was higher in MDR variant SGC7901/VCR cells than that in its parental SGC7901 cells. Moreover, DJ-1 overexpression conferred the MDR phenotype to SGC7901 cells, while DJ-1 knockdown in SGC7901/VCR cells induced re-sensitization to adriamycin, vincristine, cisplatin, and 5-fluorouracil. These results suggested that DJ-1 mediated the development of MDR in SGC7901 gastric cancer cells. Importantly, further data revealed that the activation of PI3k/Akt and Nrf2 signaling pathway were required for the DJ-1-induced MDR phenotype in SGC7901 gastric cancer cells. Meanwhile, we found that PI3k/Akt pathway was activated probably through DJ-1 directly binding to and negatively regulating PTEN, consequently resulting in Nrf2 phosphorylation and activation, and thereby inducing Nrf2-dependent P-glycoprotein (P-gp) and Bcl-2 expressions in the DJ-1-mediated MDR of SGC7901 gastric cancer cells. Overall, these results revealed that activating PTEN/PI3K/Akt/Nrf2 pathway and subsequently upregulating P-gp and Bcl-2 expression could be a critical mechanism by which DJ-1 mediates the development of MDR in SGC7901 gastric cancer cells. The new findings may be helpful for understanding the mechanisms of MDR in gastric cancer cells, prompting its further investigation as a molecular target to overcome MDR.

Glioma is diagnosed as the most common intracranial malignant tumor. Cancer stem cells determine stemness and radioresistance, and may facilitate glioma recurrence. The present study aimed to investigate whether the long non-coding RNA (lncRNA) transmembrane phosphatase with tensin homology pseudogene 1 (TPTEP1) regulated cell stemness and radioresistance of glioma, and determine the underlying molecular mechanism of TPTEP1 in the modulation of glioma progression. Cell and molecular biology techniques were applied for investigating the role of TPTEP1 in glioma cell lines, animal model, and clinical samples. The results demonstrated that TPTEP1 attenuated stemness and radioresistance of glioma both in vitro and in vivo. In addition, TPTEP1 augmented MAPK14 expression by competitively interacting with microRNA (miR)-106a-5p, thus activating the P38 MAPK signaling pathway, and suppressing glioma stemness and radioresistance. TPTEP1 functionally bound to miR-106a-5p, which formed a reciprocal regulatory loop to stimulate the P38 MAPK signaling pathway. Low TPTEP1 expression levels were detected in high-grade glioma tissues compared with low-grade glioma tissues, and were positively associated with poor prognosis of patients with glioma. Furthermore, analysis using data from The Cancer Genome Atlas database confirmed the molecular mechanism and biological significance of dysregulation of TPTEP1 in glioma progression. Taken together, the results of the present study suggest that TPTEP1 may be applied as a diagnostic and prognostic indicator for glioma, and may be an alternative target for the treatment of glioma.

We enriched a specific subpopulation of liver cancer stem cells using multiple surface markers and then cultured the cells with modified chemically defined medium to maintain the cancer stem cell properties for 2 weeks in vitro. This study may provide an effective in vitro model for the study of the biological properties of liver cancer stem cells and their use in targeted drug screening., Liver cancer stem cells (L‐CSCs) are considered to be an important therapeutic target for hepatocellular carcinoma (HCC). This study provides a new in vitro long‐term culture model for a specific subpopulation of L‐CSCs enriched by cell surface markers. We combined CD13, CD133 and EpCAM to selectively enrich L‐CSCs, which we then cultured in modified chemically defined medium. The enriched L‐CSCs exhibited enhanced proliferation, self‐renewal and long‐term clonal maintenance ability as compared with non‐CSCs. Compared with wild‐type hepatocellular carcinoma, the expression of stemness surface markers, oncogenes, drug resistance and tumorigenicity in enriched L‐CSCs was significantly increased. In summary, the subpopulation of L‐CSCs still maintains cancer stem cell‐related phenotypes after 14 days of culture.

Suppressor of Ty 16 (Spt16) is a component of the facilitates chromatin transcription (FACT) complex, which is a histone chaperone and involved in gene transcription, DNA replication, and DNA repair. Previous studies showed that FACT is highly expressed in cancer, and cancer cells are more reliant on FACT than normal cells. However, the relationship between Spt16 and lung cancer remains unclear. In this study, we explored the functions of Spt16 in lung cancer cells. The effects of Spt16 on lung cancer cell proliferation, cell cycle progression, apoptosis, migration, and invasion were examined. We found that knockdown of Spt16 led to obvious decreases of both Rb and MCM7, and further activated the DNA damage response (DDR) pathway. In addition, a novel micro‐RNA, miR‐1227‐5p, directly targeted the 3′‐UTR of Spt16 and regulated the mRNA levels of Spt16. Furthermore, we found that CBL0137, the functional inhibitor of FACT, showed similar effects as loss of Spt16. Together, our data indicated that Spt16 is likely to be an essential regulator for lung cancer malignancy and is negatively regulated by miR‐1227‐5p., In this study, we examined the functions of suppressor of Ty 16 (Spt16) in lung cancer cells. We showed that Spt16 is upregulated in lung cancers and is correlated with the poor prognosis of lung cancer patients. Knockdown of Spt16 in lung cancer cells inhibited the proliferation and metastasis of lung cancer cells both in vitro and in vivo. We also determined a novel mechanism for the regulation of Spt16 expression by miRNA‐1227‐5p.

To screen candidate marker genes implicated in vernalization, bolting-related agronomic traits and the expression of genes homologous to the bolting and flowering-related genes in Arabidopsis thaliana were investigated in KWS9147 during 16-week (w) chilling. Bolting-related agronomic traits showed that less than 10-w chilling was not sufficient for bolting. A transitional period was determined between 10 and 14 weeks when vernalization time was enough for bolting in some seedlings. After 14-w chilling, nearly all seedlings were well vernalized. At the transcriptional level, the expression of 19 candidate genes was significantly changed in response to chilling (change fold > 2 and P value

To examine the influence of epidermal growth factor (EGF) and its receptor (EGFR) on axial ocular elongation, we intraocularly injected an EGF antibody and an EGFR antibody into young guinea pigs with lens-induced axial elongation (myopization). Mean axial elongation was reduced in the eyes injected with the EGF/EGFR-antibody compared with the contralateral control eyes injected with PBS (phosphate-buffered solution) (0.43 ± 0.13 mm vs 0.53 ± 0.13 mm; P < .001). The intereye difference in axial length increased (P = .005) as the doses of the EGF antibody and EGFR antibody increased. As a corollary, the thickness of the retina at the posterior pole was dose-dependently increased in the injected eyes compared to the contralateral control eyes. Immunohistochemical staining for EGF and the relative mRNA expression of EGF and EGFR were the highest in eyes not injected with the EGF antibody or EGFR antibody and decreased (P < .05) as the dose of EGF antibody or EGFR antibody increased. In an in vitro study, EGF had a stimulating effect and the EGF antibody had an inhibitory effect on the proliferation and migration of RPE cells. The findings showed that the intravitreal application of an EGF antibody and EGFR antibody is associated with a dose-dependent reduction in lens-induced axial elongation in young guinea pigs. The EGFR family may play a role in axial elongation of the eye and in the development of myopia.

Glucose fluctuations may contribute to large conductance calcium activated potassium (BK) channel dysfunction. However, the underlying mechanisms remain elusive. The aim of this study was to investigate the molecular mechanisms involved in BK channel dysfunction as a result of glucose fluctuations. A rat diabetic model was established through the injection of streptozotocin. Glucose fluctuations in diabetic rats were induced via consumption and starvation. Rat coronary arteries were isolated and coronary vascular tensions were measured after three weeks. Rat coronary artery smooth muscle cells were isolated and whole-cell BK channel currents were recorded using a patch clamp technique. Human coronary artery smooth muscle cells in vitro were used to explore the underlying mechanisms. After incubation with iberiotoxin (IBTX), the Δ tensions (% Max) of rat coronary arteries in the controlled diabetes mellitus (C-DM), the uncontrolled DM (U-DM) and the DM with glucose fluctuation (GF-DM) groups were found to be 84.46 ± 5.75, 61.89 ± 10.20 and 14.77 ± 5.90, respectively (P .05), while the current densities of the BK channels in the three groups were 43.09 ± 4.35 pA/pF, 34.23 ± 6.07 pA/pF and 17.87 ± 4.33 pA/pF, respectively (P .05). The Δ tensions (% Max) of rat coronary arteries after applying IBTX in the GF-DM rats injected with 0.9% sodium chloride (NaCl) (GF-DM + NaCl) and the GF-DM rats injected with N-acetyl-L-cysteine (NAC) (GF-DM + NAC) groups were found to be 8.86 ± 1.09 and 48.90 ± 10.85, respectively (P .05). Excessive oxidative stress and the activation of protein kinase C (PKC) α and nuclear factor (NF)-κB induced by glucose fluctuations promoted the decrease of BK-β1 expression, while the inhibition of reactive oxygen species (ROS), PKCα, NF-κB and muscle ring finger protein 1 (MuRF1) reversed this effect. Glucose fluctuations aggravate BK channel dysfunction via the ROS overproduction and the PKCα/NF-κB/MuRF1 signaling pathway.

Hashimoto's thyroiditis (HT) is the most prevalent autoimmune thyroid disease (ATD) worldwide and is strongly associated with miscarriage and even recurrent miscarriage (RM). Moreover, with a deepening understanding, emerging evidence has shown that immune dysfunctions caused by HT conditions, including imbalanced subsets of CD4+ T-helper cells, B regulatory (Breg) cells, high expression levels of CD56dim natural killer (NK) cells, and cytokines, possibly play an important role in impairing maternal tolerance to the fetus. In recent years, unprecedented progress has been made in recognizing the specific changes in immune cells and molecules in patients with HT, which will be helpful in exploring the mechanism of HT-related miscarriage. Based on these findings, research investigating some potentially more effective treatments, such as selenium (Se), vitamin D3, and intravenous immunoglobulin (IVIG), has been well developed over the past few years. In this review, we highlight some of the latest advances in the possible immunological pathogenesis of HT-related miscarriage and focus on the efficacies of treatments that have been widely introduced to clinical trials or practice described in the most recent literature.

BackgroundExposure to zinc was suggested to be associated with pulmonary damage, but whether zinc exposure affects lung function remains unclear.ObjectivesTo quantify the association between urinary zinc and lung function and explore the potential mechanisms.MethodsUrinary zinc and lung function were measured in 3917 adults from the Wuhan-Zhuhai cohort and were repeated after 3 years of follow-up. Indicators of systemic inflammation (C reactive protein), lung epithelium integrity (club cell secretory protein-16) and oxidative damage (8-hydroxy-2′-deoxyguanosine and 8-isoprostane) were measured at baseline. Linear mixed models were used to estimate the exposure–response relationship between urinary zinc and lung function. Mediation analyses were conducted to assess mediating roles of inflammation and oxidative damage in above relationships.ResultsEach 1-unit increase in log-transformed urinary zinc values was associated with a 35.72 mL decrease in forced vital capacity (FVC) and a 24.89 mL decrease in forced expiratory volume in 1 s (FEV1) in the baseline analyses. In the follow-up analyses, there was a negative association between urinary zinc and FVC among participants with persistent high urinary zinc levels, with an estimated change of −93.31 mL (95% CI −178.47 to −8.14). Furthermore, urinary zinc was positively associated with restrictive ventilatory impairment. The mediation analyses suggested that C reactive protein mediated 8.62% and 8.71% of the associations of urinary zinc with FVC and FEV1, respectively.ConclusionUrinary zinc was negatively associated with lung function, and the systemic inflammation may be one of the underlying mechanisms.

A novel Gram-stain-negative strain, designated ZYY5T, was isolated from rice roots. Results of 16S rRNA gene analysis indicated that strain ZYY5T was a member of the genus Dickeya , with a highest similarity to Dickeya zeae DSM 18068T (98.5%). The major fatty acids were summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), C16:0 and summed feature 8 (C18:1 ω7c and/or C18:1 ω6c). Multi-locus sequence analysis using five concatenated genes (16S rRNA, atpD, infB, recA and gyrB) and phylogenomic analysis based on 2940 core gene sequences showed that strain ZYY5T formed a robust cluster with strains EC1, ZJU1202, DZ2Q, NCPPB 3531 and CSL RW192, while separated from the other strains of D. zeae . The orthologous average nucleotide identity (ANI) and digital DNA–DNAhybridization (dDDH) values among these six strains ranged from 96.8–99.9% and 73.7–99.8%, which supported that they were belonged to the same species. However, strain ZYY5T shared 58.4 of dDDH and 94.5% of ANI values with type strain D. zeae DSM 18068T, which were lower than the proposed species boundary cut-off for dDDH and ANI. The genomic analysis revealed that strain ZYY5T contained virulence-associated genes, which is same as the phylogenetic-related strains of the genus Dickeya . Based on the results of the polyphasic approaches, we propose that strain ZYY5T represents a novel species in the genus Dickeya , for which the name Dickeya oryzae sp. nov. (=JCM 33020 T=ACCC 61554 T) is proposed. Strains EC1, ZJU1202, DZ2Q, NCPPB 3531 and CSL RW192 should also be classified in the same genomospecies of D. oryzae same as ZYY5T.