MAPK20-mediated ATG6 phosphorylation is critical for pollen development in Solanum lycopersicum L.

In flowering plants, male gametogenesis is tightly regulated by numerous genes. Mitogen-activated protein kinase (MAPK) plays a critical role in plant development and stress response, while its role in plant reproductive development is largely unclear. The present study demonstrated MAPK20 phosphorylation of ATG6 to mediate pollen development and germination in tomato (Solanum lycopersicum L.). MAPK20 was preferentially expressed in the stamen of tomato, and mutation of MAPK20 resulted in abnormal pollen grains and inhibited pollen viability and germination. MAPK20 interaction with ATG6 mediated the formation of autophagosomes. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis showed that ATG6 was phosphorylated by MAPK20 at Ser-265. Mutation of ATG6 in wild-type (WT) or in MAPK20 overexpression plants resulted in malformed and inviable pollens. Meanwhile, the number of autophagosomes in mapk20 and atg6 mutants was significantly lower than that of WT plants. Our results suggest that MAPK20-mediated ATG6 phosphorylation and autophagosome formation are critical for pollen development and germination.

Efficacy and safety of high-dose ilaprazole-amoxicillin dual therapy for Helicobacter pylori eradication: a prospective, single-center, randomized trial.

Background: Until now, there have been no randomized controlled trials directly evaluating the efficacy of high-dose ilaprazole-amoxicillin dual therapy (HT) in comparison to other standard treatments for H. pylori (Helicobacter pylori) infection. This study aimed to compare the effectiveness and safety of HT with bismuth quadruple therapy (BQT) as an initial treatment for H. pylori. Methods: This single-center, prospective, randomized clinical controlled trial recruited 225 consecutive patients. They were assigned to either HT group (ilaprazole, 10 mg, twice daily; amoxicillin 1,000 mg, three times daily) or BQT group (compound bismuth aluminate granules, 2.6 g, three times daily; ilaprazole, 5 mg, twice daily; amoxicillin, 1,000 mg, twice daily; clarithromycin, 500 mg, twice daily) for 14 days. The 13C-urea breath test assessed eradication success 4 weeks after treatment. The primary outcome focused on the eradication rate, with secondary outcomes including safety and compliance. Results: From February 2023 to March 2023, 228 subjects were screened, and 225 were randomized. The HT and BQT groups showed eradication rates of 76.3% and 61.3% (p = 0.015) both by intention-to-treat (ITT) analysis and per-protocol (PP) analysis. HT was associated with fewer adverse events than BQT (27.2% vs. 81.8%, p = 0.002). The most commonly reported adverse events was bitter taste of mouth (3.5% vs. 60.4%, p < 0.001). There was no significant difference in compliance between the two groups (89.5% vs. 92.8%, p = 0.264). Conclusion: The 14-day HT treatment demonstrates better efficacy in H. pylori eradication treatment and improved safety and compliance compared to BQT. The results provide supporting evidence for 14-day HT can be potentially considered as a first-line regimen for empirical treatment. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=186562, identifier ChiCTR2200066284.

One-pot synthesis of NiFe nanoarrays under an external magnetic field as an efficient oxygen evolution reaction catalyst.

Designing and developing earth-abundant electrocatalysts for the oxygen evolution reaction (OER) in alkaline media is a critical element in the societal development of sustainable energy. MIL-53(Fe-Ni)/NF-2200Gs was synthesized under an external magnetic field. Such MIL-53(Fe-Ni)/NF-2200Gs show exceptionally high catalytic activity and require an overpotential of only 174 mV to drive a geometrical catalytic current density of 10 mA cm-2 in 1.0 M KOH, superior to RuO2 and most Fe, Ni-based electrocatalysts. Our work emphasizes the optimization of catalytic activity originating from the improvement of the magnetic properties of the catalyst, which enhances the spin polarization and tailors the d-electron structure of cations, leading to outstanding OER activity. This work would open new opportunities to design and develop transition-metal-based nanometer arrays toward efficient and stable water oxidation in alkaline media for applications.

HsfA1a confers pollen thermotolerance through upregulating antioxidant capacity, protein repair, and degradation in Solanum lycopersicum L.

The heat shock transcription factors (Hsfs) play critical roles in plant responses to abiotic stresses. However, the mechanism of Hsfs in the regulation of pollen thermotolerance and their specific biological functions and signaling remain unclear. Herein, we demonstrate that HsfA1a played a key role in tomato pollen thermotolerance. Pollen thermotolerance was reduced in hsfA1a mutants but was increased by hsfA1a overexpression, based on pollen viability and germination. Analyzing the whole transcriptome by RNA-seq data, we found that HsfA1a mainly regulated the genes involved in oxidative stress protection, protein homeostasis regulation and protein modification, as well as the response to biological stress in anthers under heat stress. The accumulation of reactive oxygen species in anthers was enhanced in hsfA1a mutants but decreased in HsfA1a-overexpressing lines. Furthermore, HsfA1a bound to the promoter region of genes involved in redox regulation (Cu/Zn-SOD, GST8, and MDAR1), protein repair (HSP17.6A, HSP70-2, HSP90-2, and HSP101) and degradation (UBP5, UBP18, RPN10a, and ATG10) and regulated the expression of these genes in tomato anthers under heat stress. Our findings suggest that HsfA1a maintains pollen thermotolerance and cellular homeostasis by enhancing antioxidant capacity and protein repair and degradation, ultimately improving pollen viability and fertility.

Peripheral Repetitive Transcranial Magnetic Stimulation(rTMS) for Idiopathic Facial Nerve Palsy: A Prospective, Randomized Controlled Trial.

Purpose: The purpose of this study was to evaluate the clinical efficacy of peripheral repetitive transcranial magnetic stimulation (rTMS) in the treatment of idiopathic facial paralysis, to explore an ideal treatment scheme for idiopathic facial paralysis, and to provide evidence for clinical rehabilitation. Methods: 65 patients with idiopathic facial nerve palsy with the first onset were recruited and randomly divided into rTMS group and control group. Both groups received conventional treatment, rTMS group received additional repetitive transcranial magnetic stimulation to the affected side once a day, 5 times a week for 2 weeks. House-Brackmann (HB) grading scale, Sunnybrook facial grading system (SFGS), and modified Portmann scale (MPS) were used to assess facial nerve function before and after treatment, and the time for patients to return to normal facial nerve function and adverse reaction (AR) was also the main observation index. Results: After a 2-week intervention, HB, SFGS, and MPS increased in both groups (P < 0.01); the improvement of HB, SFGS, and MPS in rTMS group was significantly higher than that in control group (P < 0.01). The effective improvement rate of the TMS group after 2 weeks was 90.0%, and that of the control group was 53.3%, and the difference was statistically significant (P < 0.01). Conclusions: Repetitive transcranial magnetic stimulation is a safe and effective noninvasive method for the treatment of idiopathic facial paralysis, which can significantly accelerate the recovery of facial nerve function and provide a new treatment idea for further improving the prognosis of patients with idiopathic facial paralysis.

Autophagic pathway contributes to low-nitrogen tolerance by optimizing nitrogen uptake and utilization in tomato.

Autophagy is a primary process involved in the degradation and reuse of redundant or damaged cytoplasmic components in eukaryotes. Autophagy has been demonstrated to facilitate nutrient recycling and remobilization by delivering intracellular materials to the vacuole for degradation in plants under nutrient starvation. However, the role of autophagy in nitrogen (N) uptake and utilization remains unknown. Here, we report that the ATG6-dependent autophagic pathway regulates N utilization in tomato (Solanum lycopersicum) under low-nitrogen (LN) conditions. Autophagy-disrupted mutants exhibited weakened biomass production and N accumulation compared with wild-type (WT), while ATG6 overexpression promoted autophagy and biomass production under LN stress. The N content in atg6 mutants decreased while that in ATG6-overexpressing lines increased due to the control of N transporter gene expression in roots under LN conditions. Furthermore, ATG6-dependent autophagy enhanced N assimilation efficiency and protein production in leaves. Nitrate reductase and nitrite reductase activities and expression were compromised in atg6 mutants but were enhanced in ATG6-overexpressing plants under LN stress. Moreover, ATG6-dependent autophagy increased plant carbon fixation and photosynthetic capacity. The quantum yield of photosystem II, photosynthetic N use efficiency and photosynthetic protein accumulation were compromised in atg6 mutants but were restored in ATG6-overexpressing plants. A WT scion grafted onto atg6 mutant rootstock and an atg6 scion grafted onto WT rootstock both exhibited inhibited LN-induced autophagy and N uptake and utilization. Thus, ATG6-dependent autophagy regulates not only N uptake and utilization as well as carbon assimilation but also nutrient recycling and remobilization in tomato plants experiencing LN stress.

Functions of Redox Signaling in Pollen Development and Stress Response.

Cellular redox homeostasis is crucial for normal plant growth and development. Each developmental stage of plants has a specific redox mode and is maintained by various environmental cues, oxidants, and antioxidants. Reactive oxygen species (ROS) and reactive nitrogen species are the chief oxidants in plant cells and participate in cell signal transduction and redox balance. The production and removal of oxidants are in a dynamic balance, which is necessary for plant growth. Especially during reproductive development, pollen development depends on ROS-mediated tapetal programmed cell death to provide nutrients and other essential substances. The deviation of the redox state in any period will lead to microspore abortion and pollen sterility. Meanwhile, pollens are highly sensitive to environmental stress, in particular to cell oxidative burst due to its peculiar structure and function. In this regard, plants have evolved a series of complex mechanisms to deal with redox imbalance and oxidative stress damage. This review summarizes the functions of the main redox components in different stages of pollen development, and highlights various redox protection mechanisms of pollen in response to environmental stimuli. In continuation, we also discuss the potential applications of plant growth regulators and antioxidants for improving pollen vigor and fertility in sustaining better agriculture practices.

Brassinosteroid-mediated reactive oxygen species are essential for tapetum degradation and pollen fertility in tomato.

Phytohormone brassinosteroids (BRs) are essential for plant growth and development, but the mechanisms of BR-mediated pollen development remain largely unknown. In this study, we show that pollen viability, pollen germination and seed number decreased in the BR-deficient mutant d^im , which has a lesion in the BR biosynthetic gene DWARF (DWF), and in the bzr1 mutant, which is deficient in BR signaling regulator BRASSINAZOLE RESISTANT 1 (BZR1), compared with those in wild-type plants, whereas plants overexpressing DWF or BZR1 exhibited the opposite effects. Loss or gain of function in the DWF or BZR1 genes altered the timing of reactive oxygen species (ROS) production and programmed cell death (PCD) in tapetal cells, resulting in delayed or premature tapetal degeneration, respectively. Further analysis revealed that BZR1 could directly bind to the promoter of RESPIRATORY BURST OXIDASE HOMOLOG 1 (RBOH1), and that RBOH1-mediated ROS promote pollen and seed development by triggering PCD and tapetal cell degradation. In contrast, the suppression of RBOH1 compromised BR signaling-mediated ROS production and pollen development. These findings provide strong evidence that BZR1-dependent ROS production plays a critical role in the BR-mediated regulation of tapetal cell degeneration and pollen development in Solanum lycopersicum (tomato) plants.

Melatonin promotes metabolism of bisphenol A by enhancing glutathione-dependent detoxification in Solanum lycopersicum L.

Bisphenol A (BPA), a widely distributed organic compound, is toxic to animals and plants. Here we show the mechanism of BPA detoxification by melatonin (MEL) in tomato, which is otherwise poorly understood in plants. BPA treatment decreased the quantum yield of photosystem II (Fv/Fm) and increased the membrane lipid peroxidation and reactive oxygen species (ROS) accumulation dose-dependently, whereas exogenous MEL alleviated the BPA effects on Fv/Fm, lipid peroxidation, ROS accumulation and BPA uptake. Furthermore, BPA elevated the glutathione (GSH) content, activities of glutathione S-transferase (GST), and glutathione reductase (GR), and the transcript levels of GSH1, GR1, GST1 and MEL biosynthesis genes (COMT, T5H, and SNAT), whereas BPA + MEL showed even a more profound induction. Silencing GSH1, GR1 and GST1 genes compromised the BPA detoxification potential of tomato plants as revealed by an increased level of ROS, lipid peroxidation and BPA uptake, and a decreased Fv/Fm and GST activity; these changes were alleviated by MEL application. Under in vitro conditions, BPA was glutathionylated by GSH, which was further catalyzed by GST to cysteine and N-acetylcysteine conjugates. These findings suggest a crucial role for MEL in BPA detoxification via GSH and GST, and can be useful to reduce BPA residue for food safety.

Efficacy of biological response modifier lentinan with chemotherapy for advanced cancer: a meta-analysis.

Lentinan is a common biological response modifier. This study was sought to evaluate the efficacy of adjuvant lentinan combined with chemotherapy for advanced cancer. A meta-analysis of published prospective controlled trials investigating the effects of lentinan for kinds of advanced cancer was performed. Sensitivity analysis, inverted funnel plots, and trial sequence analysis were conducted to explore the reliability and stability of results. Seventeen clinical studies were identified containing 1423 patients. Twelve trials included gastrointestinal cancer (GIC), three trials included lung cancer (LC), and two trials included the two cancers. There was a increase in survival rate in 1 year (risk ratios [RR], 1.46, P = 0.001) and overall response rate including both complete and partial response (RR, 1.28, P = 0.005). There was also a reduction in progressive disease (RR, 0.57, P = 0.0005), nonsevere adverse events (RR, 0.88, P = 0.004), and severe adverse events (RR, 0.73, P = 0.007). Similar results were shown in the two subgroups of GIC and LC. Limited trials reported the data of median overall survival and time to treatment failure, and the data were insufficient for quantitative analysis, and no significant difference were found in 2-year survival rate. Adjuvant lentinan used with chemotherapy achieved improvements in 1-year survival rate, response rate, and adverse events in advanced cancer. The effect seemed to be similar irrespective of cancer type. However, its sustained efficacy on survival was still unclear.

Histochemical studies on intestinal metaplasia adjacent to gastric cardia adenocarcinoma in subjects at high-incidence area in Henan, north China.

AIM: To characterize the histochemical type and pattern of intestinal metaplasia (IM) adjacent to gastric cardia adenocarcinoma (GCA) and distal gastric cancer (GC) in Linzhou, Henan Province, China. METHODS: Alcian-blue-periodic acid Schiff and high iron diamine-Alcian blue histochemical methods were performed on 142 cases of IM, including 49 cases of GCA and 93 cases of GC. All the patients were from Linzhou, Henan Province, China, the highest incidence area for both GCA and squamous cell carcinoma. Radio- or chemotherapy was not applied to these patients before surgery. RESULTS: The detection rate of IM in tissues adjacent to GCA tissues was 44.9%, which was significantly lower than that in GC tissues (80.64%, P<0.01). The rates of both incomplete small intestinal and colonic IM types identified by histochemistry in GCA tissues (31.82% and 63.64%, respectively) were significantly higher than those in GC (5.33% and 21.33%, respectively, P<0.01). CONCLUSION: IM in GCA and GC should be considered as a separate entity. Further research is needed to evaluate whether neoplastic progression of IM is related to its mucin profile in GCA.