Cell wall invertase 3 plays critical roles in providing sugars during pollination and fertilization in cucumber.

In plants, pollen-pistil interactions during pollination and fertilization mediate pollen hydration and germination, pollen tube growth, and seed set and development. Cell wall invertases (CWINs) help provide the carbohydrates for pollen development; however, their roles in pollination and fertilization have not been well established. In cucumber (Cucumis sativus), CsCWIN3 showed the highest expression in flowers, and we further examined CsCWIN3 for functions during pollination to seed set. Both CsCWIN3 transcript and CsCWIN3 protein exhibited similar expression patterns in the sepals, petals, stamen filaments, anther tapetum, and pollen of male flowers, as well as in the stigma, style, transmitting tract, and ovule funiculus of female flowers. Notably, repression of CsCWIN3 in cucumber did not affect the formation of parthenocarpic fruit but resulted in an arrested growth of stigma integuments in female flowers and a partially delayed dehiscence of anthers with decreased pollen viability in male flowers. Consequently, the pollen tube grew poorly in the gynoecia after pollination. In addition, CsCWIN3-RNA interference plants also showed affected seed development. Considering that sugar transporters could function in cucumber fecundity, we highlight the role of CsCWIN3 and a potential close collaboration between CWIN and sugar transporters in these processes. Overall, we used molecular and physiological analyses to determine the CsCWIN3-mediated metabolism during pollen formation, pollen tube growth, and plant fecundity. CsCWIN3 has essential roles from pollination and fertilization to seed set but not parthenocarpic fruit development in cucumber.

Recombinant Human Adenovirus Type 5 (H101) Intra-Tumor Therapy in Patients with Persistent, Recurrent, or Metastatic Cervical Cancer: Genomic Profiling Relating to Clinical Efficacy.

Objective: Genomic profiles relating to H101 treatment-induced alterations are yet to be achieved. Here, we evaluated the impact of H101 via exome-sequencing approaches aiming to probe for potential biomarkers that are actionable in the treatment of persistent/recurrent/metastatic (P/R/M) cervical cancer. Methods: Whole exome sequencing (WES) was performd on paired pre- and post-H101 samples from 17 P/R/M cervical cancer patients who received serial intra-tumor injections of H101. Somatic mutations, including high-frequency mutations, microsatellite instability (MSI) status, tumor mutation burden (TMB), clonal evolution, and mutational signature were analyzed. Results: The median follow-up time after the H101 treatment was 14 months. Complete response was achieved in 9 patients, 3 patients achieved partial response, and 2 patients had stable disease, resulting in an objective response rate (ORR) of 70.6% (95% CI: 46.4%-96.7%). WES analysis showed no difference in treatment-related mutation characteristics, including non-synonymous-SNVs and TMB status. Patients with lower TMB were correlated with improved H101 response rates (P=0.044), whereas the same was not evident in high MSI (MSI-H) versus non-MSI-H patients (P=0.528). We observed a few high-frequency mutation genes (TTN, KMT2D, ALDOA, DNAH7, ADAP1, PTPN23, and THEMIS2) that probably carry functional importance in response to H101 treatment, among which KMT2D and ADAP1 mutations were associated with inferior progression-free survival (PFS) and/or overall survival (OS) (P<0.05). Notably, H101 treatment-induced accumulating subclones or clusters in primary tumors and some (Signature 2) were associated with shorter PFS. Conclusion: We conducted an unprecedented work via a WES-based approach and provided preliminary insights into H101 treatment-induced genetic aberrations in which some genes (TTN, KMT2D, ALDOA, DNAH7, ADAP1, PTPN23, and THEMIS2) could be considered potential therapeutic targets of H101-containing treatment in cervical carcinoma. Moreover, the therapy-associated characteristics such as clonal evolution and a mutational signature may warrant further evaluation of H101 in clinical settings for treating cervical carcinoma.

Advances in the clinical development of oncolytic viruses.

OBJECTIVES: Oncolytic viruses (OVs) are natural or recombinant viruses that selectively infect and kill cancer cells without harming normal cells. This review aimed to explore some ongoing and completed clinical studies on OVs, in China and worldwide, to depict a comprehensive landscape of OV clinical trials, and summarize the existing evidence on safety and effectiveness of oncolytic therapy against tumors. METHODS: Used the Center for Drug Evaluation of China National Medical Products Administration (NMPA), Chinese Clinical Trial Registry (ChiCTR), International Clinical Trials Registry Platform, ClinicalTrials.gov website, China National Knowledge Infrastructure (CNKI), and PubMed. RESULTS: As of October 1, 2021, 408 clinical trials on 31 OV products have been conducted, with oncolytic DNA viruses being the most investigated ones; phase I and phase II clinical studies accounted for approximately 80% of all studies. Published clinical studies have shown that OVs, such as H101, T-VEC, G47Δ, OH2, T3011, and Pelareorep, have significant anti-tumor effects on various tumors, with only mild adverse events. When OVs are used together with antiviral drugs in the clinic, drug interactions should be considered based on the sensitivity of OVs to antiviral drugs. CONCLUSIONS: OVs exhibit accurate oncolysis and favorable safety, and have positive effects on a variety of tumor treatments. It is worth noting that most of the OVs under development are still in their early stages, which is both a challenge and a promising prospect.

Oncolytic Virotherapy in Peritoneal Metastasis Gastric Cancer: The Challenges and Achievements.

Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer death globally. Although the mortality rate in some parts of the world, such as East Asia, is still high, new treatments and lifestyle changes have effectively reduced deaths from this type of cancer. One of the main challenges of this type of cancer is its late diagnosis and poor prognosis. GC patients are usually diagnosed in the advanced stages of the disease, which is often associated with peritoneal metastasis (PM) and significantly reduces survival. This type of metastasis in patients with GC poses a serious challenge due to limitations in common therapies such as surgery and tumor resection, as well as failure to respond to systemic chemotherapy. To solve this problem, researchers have used virotherapy such as reovirus-based anticancer therapy in patients with GC along with PM who are resistant to current chemotherapies because this therapeutic approach is able to overcome immune suppression by activating dendritic cells (DCs) and eventually lead to the intrinsic activity of antitumor effector T cells. This review summarizes the immunopathogenesis of peritoneal metastasis of gastric cancer (PMGC) and the details for using virotherapy as an effective anticancer treatment approach, as well as its challenges and opportunities.

Alkaline α-galactosidase 2 (CsAGA2) plays a pivotal role in mediating source-sink communication in cucumber.

Sugars are necessary for plant growth and fruit development. Cucumber (Cucumis sativus L.) transports sugars, mainly raffinose family oligosaccharides (RFOs), in the vascular bundle. As the dominant sugars in cucumber fruit, glucose and fructose are derived from sucrose, which is the product of RFO hydrolysis by α-galactosidase (α-Gal). Here, we characterized the cucumber alkaline α-galactosidase 2 (CsAGA2) gene and found that CsAGA2 has undergone human selection during cucumber domestication. Further experiments showed that the expression of CsAGA2 increases gradually during fruit development, especially in fruit vasculature. In CsAGA2-RNA interference (RNAi) lines, fruit growth was delayed because of lower hexose production in the peduncle and fruit main vascular bundle (MVB). In contrast, CsAGA2-overexpressing (OE) plants displayed bigger fruits. Functional enrichment analysis of transcriptional data indicated that genes related to sugar metabolism, cell wall metabolism, and hormone signaling were significantly downregulated in the peduncle and fruit MVBs of CsAGA2-RNAi plants. Moreover, downregulation of CsAGA2 also caused negative feedback regulation on source leaves, which was shown by reduced photosynthetic efficiency, fewer plasmodesmata at the surface between mesophyll cell and intermediary cell (IC) or between IC and sieve element, and downregulated gene expression and enzyme activities related to phloem loading, as well as decreased sugar production and exportation from leaves and petioles. The opposite trend was observed in CsAGA2-OE lines. Overall, we conclude that CsAGA2 is essential for cucumber fruit set and development through mediation of sugar communication between sink strength and source activity.

Single-Wedge Lift-Out for Atom Probe Tomography Al/Ni Multilayers Specimen Preparation Based on Dual-Beam-FIB.

Atomic probe tomography (APT) samples with Al/Ni multilayer structure were successfully prepared by using a focused ion beam (FIB), combining with a field emission scanning electron microscope, with a new single-wedge lift-out method and a reduced amorphous damage layer of Ga ions implantation. The optimum vertex angle and preparation parameters of APT sample were discussed. The double interdiffusion relationship of the multilayer films was successfully observed by the local electrode APT, which laid a foundation for further study of the interface composition and crystal structure of the two-phase composites.

Efficient electrochemical degradation of tetrabromobisphenol A using MnO2/MWCNT composites modified Ni foam as cathode: Kinetic analysis, mechanism and degradation pathway.

In this study, MnO2/MWCNT hybrids, prepared using a solvothermal method, were coated onto Ni foam and then used as a cathode for tetrabromobisphenol A (TBBPA) degradation. The reaction was confirmed to exhibit the pseudo first-order kinetics. Compared with the original Ni foam cathode, the fabricated electrode exhibited higher catalytic activity, attributed to its strong cross-linking and ability to produce catalytic free radicals. Radical scavenger experiments revealed that O2- and OH were involved in the decomposition of TBBPA. The effects of current density, pH, catalyst dosage, and initial TBBPA concentration on removal efficiency were further studied. An optimal removal rate of 98.3% was achieved while the rate constant reached values up to 0.07293 min-1 and the debromination rate was more than 75.4% within 60 min. The electrode showed high catalytic performance and low catalyst loss after 10 cycles, indicating its excellent stability and reusability. The probable mechanism and pathway of TBBPA degradation were suggested based on the analysis of intermediate products. It could be inferred that the decomposition of TBBPA involved CC bond breaks (oxidation) and debromination (reduction). The MnO2/MWCNT-Ni foam could be a promising cathode material for electrochemical degradation of halogenated organic compounds.

Heterogeneous Fenton degradation of bisphenol A using Fe3O4@ß-CD/rGO composite: Synergistic effect, principle and way of degradation.

In this study, a multi-component catalyst, ß-cyclodextrin (ß-CD) and reduced graphene oxide (rGO) co-modified Fe3O4, was fabricated via one-pot solvothermal method and used as a synergistic catalyzer for Bisphenol A (BPA) removal. The study found that catalytic reactions of BPA followed the pseudo-first-order kinetics model, and the correlation rate constants (kobs) were calculated. Compared with Fe3O4@ß-CD (0.02173 min-1), Fe3O4/rGO (0.09735 min-1) and Fe3O4 (0.01666 min-1), the composite (0.15733 min-1) exhibited stronger catalytic ability to remove BPA from aqueous solution under the same conditions, which were attributed to the synergistic enhancement effect among the components. The introduction of rGO in the composites was beneficial to the generation of •OH, and the role of ß-CD might enhance the utilization of •OH. A possible three-element catalytic schematic diagram was described. The effects of pH, dosage of the catalyst, initial H2O2 and NH2OH concentrations on the removal efficiency were further investigated. The removal of BPA and TOC retained 78.2 ±â€¯2.4% and 52.9 ±â€¯2.5% after five cycles, indicating its excellent stability and reusability. Furthermore, a probable reaction pathway of BPA removal was suggested by analyzing the intermediate products. All results indicated that the composite had high and stable catalytic performance, which made it have potential application on the industrial treatment of wastewater.

Establishing a health risk assessment for metal speciation in soil-A case study in an industrial area in China.

An improved method was proposed which integrates the distribution of metal speciation simulated by chemical equilibrium model, different exposure models and average daily intake dose modified by analytic hierarchy process for human health risk assessment of metal species (MS). With the rapid development of economic and urbanization, the metals pollution had become more serious in industrial areas. Adverse effects of soil contaminants on human health in typical industrial area should be assessed to evaluate the risks of soils in these areas. The method was applied to study nickel (Ni) species health risks in soil of industrial areas. The pH possessed significant impact to determine distribution/existence and solubility of Ni species, followed by DOC. The non-carcinogenic risk (HQ) of Ni species were less than 1 in each sampling points, except Ni2+. In addition, the carcinogenic risk (CR) of different Ni species were less than 10-6, except for FANi and Ni2+.

High efficiency and rapid degradation of bisphenol A by the synergy between adsorption and oxidization on the MnO2@nano hollow carbon sphere.

In this research, a novel efficiency MnO2@Nano hollow carbon sphere (MnO2@NHCS) nanocomposite was prepared by one-pot hydrothermal reaction with KMnO4 solution. The adsorption and oxidization performance of MnO2@NHCS were assessed by degradation of bisphenol A (BPA) at different conditions. The effect of dosage of MnO2@NHCS, pH, initial concentration of BPA, temperature and humic acid were investigated systematically. Moreover, the characterizations of MnO2@NHCS were measured by a series of techniques, such as XRD, FESEM, HRTEM, TGA and XPS. Notably, hollow structure of nano carbon sphere was still retained with uniform MnO2 nanosheets covered. The results show that the removal rate of BPA was 95.3% within 10 min and BPA can be almost decomposed in 30 min under the optimal conditions. Additionally, the MnO2@NHCS remained stable and had a high regeneration efficiency (more than 85%) after 3 cycles (360 min). The reaction intermediates/products of oxidation of BPA were analyzed and the possible degradation pathways of BPA were proposed. These research results demonstrate that the MnO2@NHCS is a fleet and efficient material for BPA degradation in aqueous environment.

Establishing a method to assess comprehensive effect of gradient variation human health risk to metal speciation in groundwater.

A method was proposed to evaluate comprehensive effects of pHs and total metal concentration (TMC) variation for metal speciation human health risk in groundwater. The method used for the health assessment considered comprehensive and mutative effects caused by oral ingestion of groundwater based on human health risk assessment model and MINTEQ simulation. The results demonstrated that the dissolution rate of Ni2+ was affected by pH and Ni total concentration (total-Ni). With the increase of pH, the Ni2+ dissolved rate was smaller in the higher total-Ni at same pH. Ni2+ was dominant components contributed to health risk in groundwater. With the increase of pH in various total-Ni, HINi keep constant at first, and then decreased gradually. The HINi values of Ni speciation above acceptable level only in high total-Ni with alkaline conditions. The obtained results to verify that metals speciation were determined in health risk, and variation factors (pH and metal total concentration) played important role in risk estimation. These results provide basic information of heavy metal pollution control as well as remediation management.

Methodology of spatial risk assessment for arsenic species associated with sampling and analysis results optimization.

The conventional risk assessment methods may be defective for more effective health risk assessment due to ignoring heavy metal species and the accuracy and integrity of sampling and analysis results. Using the accurate and integral data to quantify the human health effects of metal species can provide great support for more effective health risk assessment. This study presents a new methodology to optimize sampling and analysis results for implementing the spatial human health risk of heavy metal species in contaminated sites. The method integrated Entropy method and Inverse Distance to a Power (IDW) for obtaining the effective risk, and mapping the visual risk distribution of metal species. The results of its application with ingesting arsenic via oral route on adults showed that carcinogenic and non-carcinogenic risks of As were influenced by its species. The risk of HAsO4-2, H3AsO3, H2AsO4-, H2AsO3- and AsS(OH)HS- exceeded threshold that was significantly harmful to human health in study area. This method broadened the scope of human health risk assessment and provided a basis for government policy-making and site remediation.