Depletion of SLC7A11 Sensitizes Nasopharyngeal Carcinoma Cells to Ionizing Radiation.

BACKGROUND: Radiotherapy is the primary treatment choice for Nasopharyngeal Carcinoma (NPC). However, its efficacy is compromised due to radioresistance. Ferroptosis, a novel iron-dependent regulated cell death induced by Ionizing Radiation (IR), plays a role in promoting cancer cell death. Yet, the relationship between enhanced ferroptosis and increased sensitivity of NPC cells to IR remains poorly understood. OBJECTIVE: This study aimed to explore the association between IR and ferroptosis in NPC, as well as the role of the ferroptosis repressor SLC7A11 in IR-treated NPC cells. METHODS: CNE1 and HNE-2 NPC cells were subjected to IR treatment. We performed qPCR and western blotting to evaluate the expression of ferroptosis-related genes in both control and IR-treated NPC cells. Additionally, we used the MTT assay to measure the viability of these NPC cells. JC-1 and DCFH-DA staining were employed to assess mitochondrial membrane potential and Reactive Oxygen Species (ROS) levels in both control and IR-treated NPC cells. Furthermore, we examined the levels of Fe2+, Malondialdehyde (MDA), reduced Glutathione (GSH), and oxidized glutathione (GSSG) in these cells. Moreover, we depleted SLC7A11 in IR-treated NPC cells to investigate its impact on the ferroptosis of these cells. RESULTS: IR upregulated the expression of ferroptosis-related genes, including SLC7A11, ACSL4, COX2, FTH1, and GPX4, in CNE1 and HNE-2 cells. IR treatment also resulted in decreased cell viability, disrupted mitochondrial membrane potential, increased ROS levels, altered glutathione levels, and elevated Fe2+ levels. Knockdown of SLC7A11 enhanced the sensitivity of NPC cells to IR. CONCLUSION: IR may induce ferroptosis in NPC cells, and stimulating ferroptosis could potentially serve as a therapeutic strategy to enhance the efficacy of IR in treating NPC patients.

A 700 nm LED Light Activated Ru(II) Complex Destroys Tumor Cytoskeleton via Photosensitization and Photocatalysis.

Photoactivable chemotherapy (PACT) using metallic complexes provides spatiotemporal selectivity over drug activation for targeted anticancer therapy. However, the poor absorption in near-infrared (NIR) light region of most metallic complexes renders tissue penetration challenging. Herein, an NIR light triggered dinuclear photoactivable Ru(II) complex (Ru2) is presented and the antitumor mechanism is comprehensively investigated. The introduction of a donor-acceptor-donor (D-A-D) linker greatly enhances the intramolecular charge transition, resulting in a high molar extinction coefficient in the NIR region with an extended triplet excited state lifetime. Most importantly, when activated by 700 nm NIR light, Ru2 exhibits unique slow photodissociation kinetics that facilitates synergistic photosensitization and photocatalytic activity to destroy diverse intracellular biomolecules. In vitro and in vivo experiments show that when activated by 700 nm NIR light, Ru2 exhibits nanomolar photocytotoxicity toward 4T1 cancer cells via the induction of calcium overload and endoplasmic reticulum (ER) stress. These findings provide a robust foundation for the development of NIR-activated Ru(II) PACT complexes for phototherapeutic application.

The Globodera rostochiensis Gr29D09 Effector with a Role in Defense Suppression Targets the Potato Hexokinase 1 Protein.

The potato cyst nematode (Globodera rostochiensis) is an obligate root pathogen of potatoes. G. rostochiensis encodes several highly expanded effector gene families, including the Gr4D06 family; however, little is known about the function of this effector family. We cloned four 29D09 genes from G. rostochiensis (named Gr29D09v1/v2/v3/v4) that share high sequence similarity and are homologous to the Hg29D09 and Hg4D06 effector genes from the soybean cyst nematode (Heterodera glycines). Phylogenetic analysis revealed that Gr29D09 genes belong to a subgroup of the Gr4D06 family. We showed that Gr29D09 genes are expressed exclusively within the nematode's dorsal gland cell and are dramatically upregulated in parasitic stages, indicating involvement of Gr29D09 effectors in nematode parasitism. Transgenic potato lines overexpressing Gr29D09 variants showed increased susceptibility to G. rostochiensis. Transient expression assays in Nicotiana benthamiana demonstrated that Gr29D09v3 could suppress reactive oxygen species (ROS) production and defense gene expression induced by flg22 and cell death mediated by immune receptors. These results suggest a critical role of Gr29D09 effectors in defense suppression. The use of affinity purification coupled with nanoliquid chromatography-tandem mass spectrometry identified potato hexokinase 1 (StHXK1) as a candidate target of Gr29D09. The Gr29D09-StHXK1 interaction was further confirmed using in planta protein-protein interaction assays. Plant HXKs have been implicated in defense regulation against pathogen infection. Interestingly, we found that StHXK1 could enhance flg22-induced ROS production, consistent with a positive role of plant HXKs in defense. Altogether, our results suggest that targeting StHXK1 by Gr29D09 effectors may impair the positive function of StHXK1 in plant immunity, thereby aiding nematode parasitism. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Horizontal middle partial laryngectomy with cricothyroidopexy: an effective treatment for stage T1b glottic carcinoma.

BACKGROUND: The current treatment options for T1b glottic carcinoma often lead to poor treatment outcomes or voice quality. OBJECTIVES: This study evaluates the therapeutic efficacy of horizontal middle partial laryngectomy with cricothyroidopexy (HMPL-CTP) for stage T1b glottic carcinoma. MATERIAL AND METHODS: A retrospective analysis was conducted on 73 patients with T1b glottic carcinoma. The patients were categorized into three groups: Group A (n = 22) underwent transoral laser microsurgery (TLMS), Group B (n = 21) received frontolateral vertical partial laryngectomy (FVPL), and Group C (n = 30) underwent HMPL-CTP. The study analyzed the 5-year overall survival rate (OS), recurrence rate, phonatory status, and incidence of laryngeal stenosis. RESULTS: Voice quality scores varied significantly in the three groups, while the 5-year OS were similar. The local recurrence rate is higher in Group A than in the other two groups. The laryngeal stenosis rate in Group B is higher than in Groups A and C. Adhesions in the anterior commissure were observed in 18 cases in Group A and nine cases in Group C. CONCLUSIONS AND SIGNIFICANCE: HMPL-CTP demonstrates efficacy as a treatment for stage T1b glottic carcinoma, offering favorable preservation of laryngeal function and minimal complications.

Three-dimensional ultrasound-based radiomics nomogram for the prediction of extrathyroidal extension features in papillary thyroid cancer.

Purpose: To develop and validate a three-dimensional ultrasound (3D US) radiomics nomogram for the preoperative prediction of extrathyroidal extension (ETE) in papillary thyroid cancer (PTC). Methods: This retrospective study included 168 patients with surgically proven PTC (non-ETE, n = 90; ETE, n = 78) who were divided into training (n = 117) and validation (n = 51) cohorts by a random stratified sampling strategy. The regions of interest (ROIs) were obtained manually from 3D US images. A larger number of radiomic features were automatically extracted. Finally, a nomogram was built, incorporating the radiomics scores and selected clinical predictors. Receiver operating characteristic (ROC) curves were performed to validate the capability of the nomogram on both the training and validation sets. The nomogram models were compared with conventional US models. The DeLong test was adopted to compare different ROC curves. Results: The area under the receiver operating characteristic curve (AUC) of the radiologist was 0.67 [95% confidence interval (CI), 0.580-0.757] in the training cohort and 0.62 (95% CI, 0.467-0.746) in the validation cohort. Sixteen features from 3D US images were used to build the radiomics signature. The radiomics nomogram, which incorporated the radiomics signature, tumor location, and tumor size showed good calibration and discrimination in the training cohort (AUC, 0.810; 95% CI, 0.727-0.876) and the validation cohort (AUC, 0.798; 95% CI, 0.662-0.897). The result suggested that the diagnostic efficiency of the 3D US-based radiomics nomogram was better than that of the radiologist and it had a favorable discriminate performance with a higher AUC (DeLong test: p < 0.05). Conclusions: The 3D US-based radiomics signature nomogram, a noninvasive preoperative prediction method that incorporates tumor location and tumor size, presented more advantages over radiologist-reported ETE statuses for PTC.

Polydopamine-cloaked Fe-based metal organic frameworks enable synergistic multidimensional treatment of osteosarcoma.

One of the major challenges in effective cancer therapy arises because of the hypoxic microenvironment in the tumor. This compromises the efficacy of both chemo- and radiotherapy, and thus hinders patient outcomes. To solve this problem, we constructed polydopamine (PDA)-cloaked Fe-based metal organic frameworks (MOFs) loaded with d-arginine (d-Arg), glucose oxidase (GOX), and the chemotherapeutic drug tirapazamine (TPZ). These offer simultaneous multifaceted therapy combining chemodynamic therapy (CDT)/radiotherapy (RT)/starvation therapy (ST)/gas therapy (GT) and chemotherapy. The particles further can act as contrast agents in magnetic resonance imaging. GOX catalyses the conversion of endogenous glucose and O2 to hydrogen peroxide and gluconic acid, blocking the cells' energy supply and providing ST. With the resultant acidification of the local environment, the breakdown of the MOF releases TPZ (for chemotherapy) and Fe3+, which reacts with H2O2 to produce reactive oxygen species and thus stimulates the conversion of d-Arg to NO for GT and RT sensitization. The PDA coating not only seals the pores and chelates Fe3+ to enhance the T1-weighted magnetic resonance imaging (MRI) properties, but also is used to graft folate bovine serum albumin (FA-BSA) and thereby target the tumor site. The combined administration of low doses of X-ray irradiation and nanoparticles reduces the side effects on healthy tissue and can prevent lung metastases in mice. This work highlights the synergistic treatment of osteosarcoma via ST/GT/CDT/RT/MRI/ chemotherapy using a PDA-cloaked MOF system.

A key virulence effector from cyst nematodes targets host autophagy to promote nematode parasitism.

Autophagy, an intracellular degradation system conserved in eukaryotes, has been increasingly recognized as a key battlefield in plant-pathogen interactions. However, the role of plant autophagy in nematode parasitism is mostly unknown. We report here the identification of a novel and conserved effector, Nematode Manipulator of Autophagy System 1 (NMAS1), from plant-parasitic cyst nematodes (Heterodera and Globodera spp.). We used molecular and genetic analyses to demonstrate that NMAS1 is required for nematode parasitism. The NMAS1 effectors are potent suppressors of reactive oxygen species (ROS) induced by flg22 and cell death mediated by immune receptors in Nicotiana benthamiana, suggesting a key role of NMAS1 effectors in nematode virulence. Arabidopsis atg mutants defective in autophagy showed reduced susceptibility to nematode infection. The NMAS1 effectors contain predicted AuTophaGy-related protein 8 (ATG8)-interacting motif (AIM) sequences. In planta protein-protein interaction assays further demonstrated that NMAS1 effectors specifically interact with host plant ATG8 proteins. Interestingly, mutation in AIM2 of GrNMAS1 from the potato cyst nematode Globodera rostochiensis abolishes its interaction with potato StATG8 proteins and its activity in ROS suppression. Collectively, our results reveal for the first time that cyst nematodes employ a conserved AIM-containing virulence effector capable of targeting a key component of host autophagy to promote disease.

[Clinical application of a self-developed mouth opener with a tongue base retractor in the operation of deep part of tongue base].

Objective:To test the application effect of a self-developed mouth opener with a tongue base retractor in the operation of the deep part of tongue base. Methods:The tongue base surgical field was exposed by using a self-developed mouth opener with a tongue base retractor in 8 patients who underwent deep tongue base operation via oral approach, the difficulty of operation, the effect of exposure of operation field, the tear of mucous membrane of the pharynx arch and the risk of tongue paralysis were observed. Results:The self-made mouth opener can expose the deep operative field of the tongue root by using the self-provided tongue root retractor during the operation, and the operation is conducted under the guidance of angle endoscope. The operative field of 8 patients was well exposed during the whole operation, there was no pharyngeal mucosa tearing and postoperative tongue paralysis. Conclusion:The self-made mouth opener has the advantages of simple operation, good exposure effect and less complications, but it needs rigid bending instruments in some operations.

Characterization and response of two potato receptor-like kinases to cyst nematode infection.

Plant-parasitic cyst nematodes (Heterodera and Globodera spp.) secrete CLAVATA3/EMBRYO SURROUNDING REGION-RELATED (CLE) effector proteins, which act as ligand mimics of plant CLE peptides to promote successful nematode infection. Previous studies of the Arabidopsis-beet cyst nematode (BCN; H. schachtii) pathosystem showed that Arabidopsis CLE receptors including CLAVATA1 (CLV1), CLV2, and RECEPTOR-LIKE PROTEIN KINASE 2 (RPK2) are required for BCN CLE signaling. Studies further revealed that nematode CLE signaling through GmCLV2 and StCLV2, an Arabidopsis CLV2 orthologue from soybean (Glycines max) and potato (Solanum tuberosum), respectively, is required for the soybean cyst nematode (SCN; H. glycines) and the potato cyst nematode (PCN; G. rostochiensis) to induce disease in their respective host plant. In this study, we identified and characterized two additional potato receptors, StRPK2 and StCLV1, homologues of Arabidopsis RPK2 and CLV1, for a role in PCN parasitism. Using promoter-reporter lines we showed that both StRPK2 and StCLV1 are expressed in the potato root but vary in their spatial expression patterns. Interestingly, StRPK2 but not StCLV1 was found to be expressed and upregulated at PCN infection sites. Nematode infection assays on StRPK2-knockdown lines revealed a decrease in nematode infection. Collectively, our results suggest that parallel CLE signaling pathways involving StCLV2 and StRPK2 are important for PCN parasitism and that manipulation of nematode CLE signaling may represent a viable means to engineer nematode resistance in crop plants including potato.

Effects of Risperidone and Prenatal Poly I:C Exposure on GABAA Receptors and AKT-GSK3ß Pathway in the Ventral Tegmental Area of Female Juvenile Rats.

The ventral tegmental area (VTA) in the ventral midbrain is the origin of the dopaminergic neurotransmission pathways. Although GABAA receptors and AKT-GSK3ß signaling are involved in the pathophysiology of mental disorders and are modulated by antipsychotics, an unmet task is to reveal the pathological changes in these biomarkers and antipsychotic modulations in the VTA. Using a juvenile polyriboinosinic-polyribocytidylic acid (Poly I:C) psychiatric rat model, this study investigated the effects of adolescent risperidone treatment on GABAA receptors and AKT/GSK3ß in the VTA. Pregnant female Sprague-Dawley rats were administered Poly I:C (5mg/kg; i.p) or saline at gestational day 15. Juvenile female offspring received risperidone (0.9 mg/kg, twice per day) or a vehicle from postnatal day 35 for 25 days. Poly I:C offspring had significantly decreased mRNA expression of GABAA receptor ß3 subunits and glutamic acid decarboxylase (GAD2) in the VTA, while risperidone partially reversed the decreased GAD2 expression. Prenatal Poly I:C exposure led to increased expression of AKT2 and GSK3ß. Risperidone decreased GABAA receptor ß2/3, but increased AKT2 mRNA expression in the VTA of healthy rats. This study suggests that Poly I:C-elicited maternal immune activation and risperidone differentially modulate GABAergic neurotransmission and AKT-GSK3ß signaling in the VTA of adolescent rats.

Map, but not EspF, induces breast epithelial cell apoptosis through ERK/DRP-1 pathway.

The incidence of bovine mastitis induced by enteropathogenic Escherichia coli (EPEC) in the environment has increased, but the mechanism of effector-Map and -EspF secreted by EPEC in breast epithelial cells is not clear. Therefore, this study focused on Map and EspF to explore the role of these two virulence factors in EPEC-induced bovine mastitis. We established Δmap and/or ΔEspF mutant strains to explore their role in EPEC-induced bovine mastitis. It was found that both Map and EspF could affect the mitochondrial membrane potential, apoptosis, and tight junctions in MAC-T cells. In addition, we also found that Map could affect the ERK signaling pathway. In order to further verify the effect of Map on the ERK signaling pathway, we introduced an ERK inhibitor (PD98059) and pc DNA3.1 plasmid with the map gene. It was found that DRP-1 and apoptosis were no longer affected by Map. In summary, the study implies that E. coli can promote breast epithelial cell apoptosis and destroy tight junctions through Map and EspF. However, Map, but not EspF, induces breast epithelial cell apoptosis through the ERK-DRP-1 pathway.

A plant cell wall-associated kinase encoding gene is dramatically downregulated during nematode infection of potato.

Plant cell wall associated kinases (WAKs) and WAK-like kinases (WAKLs) have been increasingly recognized as important regulators of plant immunity against various plant pathogens. However, the role of the WAK/WAKL family in plant-nematode interactions remains to be determined. Here, we analyzed a WAK-encoding gene (Soltu.DM.02G029720.1) from potato (Solanum tuberosum). The Soltu.DM.02G029720.1 encoded protein contains domains characteristic of WAK/WAKL proteins and shows the highest similarity to SlWAKL2 from tomato (S. lycopersicum). We thus named the gene as StWAKL2. Phylogenetic analysis of a wide range of plant WAKs/WAKLs further revealed close similarity of StWAKL2 to three WAK/WAKL proteins demonstrated to play a role in disease resistance. To gain insights into the potential regulation and function of StWAKL2, transgenic potato lines containing the StWAKL2 promoter fused to the ß-glucuronidase (GUS) reporter gene were generated and used to investigate StWAKL2 expression during plant development and upon nematode infection. Histochemical analyses revealed that StWAKL2 has specific expression patterns in potato leaf and root tissues. During nematode infection, GUS activity was mostly undetected at nematode infection sites over the course of nematode parasitism, although strong GUS activity was observed in root tissues adjacent to the infection region. Furthermore, mining of the transcriptomic data derived from cyst nematode infection of Arabidopsis roots identified a few WAK/WAKL genes, including a StWAKL2 homologue, found to be significantly down-regulated in nematode-induced feeding sites. These results indicated that specific suppression of WAK/WAKL genes in nematode-induced feeding sites might be crucial for cyst nematodes to achieve successful infection of host plants. Further studies are needed to uncover the role of WAK/WAKL genes in plant defenses against nematode infection.

Clinicopathological factors affecting the prognosis of massive hemorrhage after radiotherapy for patients having nasopharyngeal carcinoma.

AIMS: The aim of the study is to investigate the clinicopathological factors that determine prognosis of nasopharyngeal hemorrhage after radiotherapy in patients with nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: The clinicopathological data of 539 patients with NPC, who received radiotherapy, were analyzed retrospectively. Parameters included gender; age; T-stage; N-stage; pathological type; type of radiotherapy; synchronous chemotherapy; secondary-course radiotherapy; radiation-induced skull base osteonecrosis; diabetes, hypertension, or other systemic diseases; results of nasopharyngeal bacterial culture; and nasopharyngeal tumor recurrence. Univariate and multivariate analyses were performed using the Chi-square test and logistic regression. Afterward, the Kaplan-Meier's method was applied to analyze the survival of patients with nasopharyngeal hemorrhage. RESULTS: Among all patients examined, 64 (11.9%) had nasopharyngeal hemorrhage after radiotherapy. The univariate analysis showed that T-stage (P < 0.01), secondary-course radiotherapy (P < 0.01), radiation-induced skull base osteonecrosis (P < 0.01), nasopharyngeal bacterial culture results (P < 0.01), and nasopharyngeal tumor recurrence (P < 0.01) were associated with nasopharyngeal hemorrhage. Multivariate analysis showed that only radiation-induced skull base osteonecrosis was significantly associated with nasopharyngeal hemorrhage after radiotherapy (odds ratio = 41.83, P = 0.0001). Nevertheless, in patients with internal carotid artery hemorrhage, the survival rate was much lower than that in patients with external carotid artery bleeding. The main cause of death during follow-up was rebleeding. CONCLUSION: The rate of mortality in patients with nasopharyngeal hemorrhage after radiotherapy was high. The presence of radiation-induced skull base osteonecrosis was a decisive factor in these patients. However, after successful rescue, arterial embolization or stent implantation is proposed to prolong survival.

Salmonella Infantis Delays the Death of Infected Epithelial Cells to Aggravate Bacterial Load by Intermittent Phosphorylation of Akt With SopB.

Salmonella Infantis has emerged as a major clinical pathogen causing gastroenteritis worldwide in recent years. As an intracellular pathogen, Salmonella has evolved to manipulate and benefit from the cell death signaling pathway. In this study, we discovered that S. Infantis inhibited apoptosis of infected Caco-2 cells by phosphorylating Akt. Notably, Akt phosphorylation was observed in a discontinuous manner: immediately 0.5 h after the invasion, then before peak cytosolic replication. Single-cell analysis revealed that the second phase was only induced by cytosolic hyper-replicating bacteria at 3-4 hpi. Next, Akt-mediated apoptosis inhibition was found to be initiated by Salmonella SopB. Furthermore, Akt phosphorylation increased mitochondrial localization of Bcl-2 to prevent Bax oligomerization on the mitochondrial membrane, maintaining the mitochondrial network homeostasis to resist apoptosis. In addition, S. Infantis induced pyroptosis, as evidenced by increased caspase-1 (p10) and GSDMS-N levels. In contrast, cells infected with the ΔSopB strain displayed faster but less severe pyroptosis and had less bacterial load. The results indicated that S. Infantis SopB-mediated Akt phosphorylation delayed pyroptosis, but aggravated its severity. The wild-type strain also caused more severe diarrhea and intestinal inflammatory damage than the ΔSopB strain in mice. These findings revealed that S. Infantis delayed the cells' death by intermittent activation of Akt, allowing sufficient time for replication, thereby causing more severe inflammation.

Lactobacillus rhamnosus GR-1 Prevents Escherichia coli-Induced Apoptosis Through PINK1/Parkin-Mediated Mitophagy in Bovine Mastitis.

Escherichia coli is one of the most important pathogens that cause clinical mastitis in dairy cattle worldwide and lead to severe economic losses. Antibiotics are often used to treat this inflammatory disease; however, antimicrobial resistance and environmental pollution cannot be ignored. Probiotic is the best alternative; however, its mechanisms of action to prevent mastitis remain unclear. Moreover, the role of probiotics in regulating mitophagy, a selective autophagy that maintains mitochondrial quality, needs to be explored. E. coli infection induced NOD-like receptor family member pyrin domain-containing protein 3 (NLRP3) inflammasome assembly, Caspase-1 activation, and apoptosis in MAC-T cells. Infection also resulted in mitochondrial damage and subsequent increase in reactive oxygen species (ROS) production. Moreover, inhibition of ROS release by scavenger N-acetyl-L-cysteine (NAC) abrogated the importance of ROS in NLRP3 assembly and apoptosis in MAC-T cells. Pretreatment with Lactobacillus rhamnosus GR-1 (LGR-1), a probiotic, alleviated E. coli-induced NLRP3 inflammasome activation and apoptosis via ROS inhibition. Besides, E. coli infection inhibited mitophagy while LGR-1 pretreatment augmented PINK1/Parkin-mediated mitophagy activation, which further blocked ROS generation. To explore the effect of LGR-1 in vivo, a mouse mastitis model was established. The results showed that LGR-1 pretreatment had preventive and protective effects on E. coli induced mastitis, and could reduce cytokines levels such as IL-1ß and TNF-α. In accordance with the results in vitro, E. coli can inhibit mitophagy and activate NLRP3 inflammasome and apoptosis, while LGR-1 can weaken the effect of E. coli. Taken together, our data indicated that LGR-1 pretreatment induced PINK1/Parkin-mediated mitophagy that eliminated damaged mitochondria and reduced ROS production and NLRP3 inflammasome activation, which subsequently decreased E. coli-induced apoptosis. To conclude, our study suggests that therapeutic strategies aiming at the upregulation of mitophagy under E. coli-induced mastitis may preserve mitochondrial function and provide theoretical support for the application of probiotics in bovine mastitis.

Light-responsive and corrosion-resistant gas valve with non-thermal effective liquid-gating positional flow control.

Safe and precise control of gas flow is one of the key factors to many physical and chemical processes, such as degassing, natural gas transportation, and gas sensor. In practical application, it is essential for the gas-involved physicochemical process to keep everything under control and safe, which significantly relies on the controllability, safety, and stability of their valves. Here we show a light-responsive and corrosion-resistant gas valve with non-thermal effective liquid-gating positional flow control under a constant pressure by incorporating dynamic gating liquid with light responsiveness of solid porous substrate. Our experimental and theoretical analysis reveal that the photoisomerization of azobenzene-based molecular photoswitches on the porous substrate enabled the gas valve to possess a light-responsive and reversible variation of substantial critical pressure of non-thermal effective gas flow switch. Moreover, the chemically inert gating liquid prevented the solid substrate from corrosion and, by combining with the high spatiotemporal resolution of light, the gas valve realizes a precisely positional open and close under a steady-state pressure. The application demonstrations in our results show the potentials of the new gas valve for bringing opportunities to many applications, such as gas-involved reaction control in microfluidics, soft actuators, and beyond.

Reduced levels of actin gamma 1 predict poor prognosis in ovarian cancer patients.

AIM: To investigate the expression and function of actin gamma 1 (ACTG1) in ovarian cancer. METHODS: We performed immunohistochemical staining of 176 ovarian cancer tissue samples in a human tissue microarray to detect expression of ACTG1. Staining intensity was examined in relation to clinicopathological parameters. To investigate the prognostic value of ACTG1, ACTG1 mRNA data from 300 ovarian cancer patients in The Cancer Genome Atlas database were examined. RESULTS: The immunohistochemical results demonstrated that levels of ACTG1 were reduced in the samples of human ovarian cancer tissue that were examined, and the levels negatively correlated with various clinicopathological parameters. Levels of ACTG1 mRNA also negatively correlated with clinical stage. In Kaplan-Meier survival analysis, higher levels of ACTG1 mRNA were associated with improved overall survival. In multivariate analysis by Cox regression, ACTG1 expression was identified as an independent prognostic marker of favorable overall survival. CONCLUSION: ACTG1 may represent a valuable marker for the prognosis of ovarian cancer, and further studies of ACTG1 are warranted.

Soybean Resistance Locus Rhg1 Confers Resistance to Multiple Cyst Nematodes in Diverse Plant Species.

Cyst nematodes consistently threaten agricultural production, causing billions of dollars in losses globally. The Rhg1 (resistance to Heterodera glycines 1) locus of soybean (Glycine max) is the most popular resistance source used against soybean cyst nematodes (H. glycines). Rhg1 is a complex locus that has multiple repeats of an ≈30-kilobase segment carrying three genes that contribute to resistance. We investigated whether soybean Rhg1 could function in different plant families, conferring resistance to their respective cyst nematode parasites. Transgenic Arabidopsis thaliana and potato (Solanum tuberosum) plants expressing the three soybean Rhg1 genes were generated. The recipient Brassicaceae and Solanaceae plant species exhibited elevated resistance to H. schachtii and Globodera rostochiensis and to G. pallida, respectively. However, some negative consequences including reduced root growth and tuber biomass were observed upon Rhg1 expression in heterologous species. One of the genes at Rhg1 encodes a toxic version of an alpha-SNAP protein that has been demonstrated to interfere with vesicle trafficking. Using a transient expression assay for Nicotiana benthamiana, native Arabidopsis and potato alpha-SNAPs (soluble NSF [N-ethylamine sensitive factor] attachment protein) were found to compensate for the toxicity of soybean Rhg1 alpha-SNAP proteins. Hence, future manipulation of the balance between Rhg1 alpha-SNAP and the endogenous wild-type alpha-SNAPs (as well as the recently discovered soybean NSF-RAN07) may mitigate impacts of Rhg1 on plant productivity. The multispecies efficacy of soybean Rhg1 demonstrates that the encoded mechanisms can function across plant and cyst nematode species and offers a possible avenue for engineered resistance in diverse crop species.

In Vitro and In Silico Analyses of the Inhibition of Human Aldehyde Oxidase by Bazedoxifene, Lasofoxifene, and Structural Analogues.

Tamoxifen, raloxifene, and nafoxidine are selective estrogen receptor modulators (SERMs) reported to inhibit the catalytic activity of human aldehyde oxidase 1 (AOX1). How these drugs interact with AOX1 and whether other SERMs inhibit this drug-metabolizing enzyme are not known. Therefore, a detailed in vitro and in silico study involving parent drugs and their analogs was conducted to investigate the effect of specific SERMs, particularly acolbifene, bazedoxifene, and lasofoxifene on AOX1 catalytic activity, as assessed by carbazeran 4-oxidation, an AOX1-selective catalytic marker. The rank order in the potency (based on IC50 values) of AOX1 inhibition by SERMs was raloxifene > bazedoxifene ∼ lasofoxifene > tamoxifen > acolbifene. Inhibition of liver cytosolic AOX1 by bazedoxifene, lasofoxifene, and tamoxifen was competitive, whereas that by raloxifene was noncompetitive. Loss of 1-azepanylethyl group increased the inhibitory potency of bazedoxifene, whereas the N-oxide group decreased it. The 7-hydroxy group and the substituted pyrrolidine ring attached to the tetrahydronaphthalene structure contributed to AOX1 inhibition by lasofoxifene. These results are supported by molecular-docking simulations in terms of predicted binding modes, encompassing binding orientation and efficiency, and analysis of key interactions, particularly hydrogen bonds. The extent of AOX1 inhibition by bazedoxifene was increased by estrone sulfate and estrone. In summary, SERMs differentially inhibited human AOX1 catalytic activity. Structural features of bazedoxifene and lasofoxifene contributed to AOX1 inhibition, whereas those of acolbifene rendered it considerably less susceptible to AOX1 inhibition. Overall, our novel biochemical findings and molecular-docking analyses provide new insights into the interaction between SERMs and AOX1. SIGNIFICANCE STATEMENT: Aldehyde oxidase (AOX1) is a molybdo-flavoprotein and has emerged as a drug-metabolizing enzyme of potential therapeutic importance because drugs have been identified as AOX1 substrates. Selective estrogen receptor modulators (SERM), which are drugs used to treat and prevent various conditions, differentially inhibit AOX1 catalytic activity. Structural features of bazedoxifene and lasofoxifene contribute to AOX1 inhibition, whereas those of acolbifene render it considerably less susceptible to AOX1 inhibition. Our novel biochemical findings, together with molecular- docking analyses, provide new insights into the differential inhibitory effect of SERMs on the catalytic activity of human AOX1, how SERMs bind to AOX1, and increase our understanding of the AOX1 pharmacophore in the inhibition of AOX1 by drugs and other chemicals.