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Abstract Background L-theanine is a unique non-protein amino acid in tea that is widely used as a safe food additive. We investigated the cardioprotective effects and mechanisms of L-theanine in myocardial ischemia-reperfusion injury (MIRI). Methods The cardioprotective effects and mechanisms of L-theanine and the role of Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling were investigated in MIRI mice using measures of cardiac function, oxidative stress, and apoptosis. Results Administration of L-theanine (10 mg/kg, once daily) suppressed the MIRI-induced increase in infarct size and serum creatine kinase and lactate dehydrogenase levels, as well as MIRI-induced cardiac apoptosis, as evidenced by an increase in Bcl-2 expression and a decrease in Bax/caspase-3 expression. Administration of L-theanine also decreased the levels of parameters reflecting oxidative stress, such as dihydroethidium, malondialdehyde, and nitric oxide, and increased the levels of parameters reflecting anti-oxidation, such as total antioxidant capacity (T-AOC), glutathione (GSH), and superoxide dismutase (SOD) in ischemic heart tissue. Further analysis showed that L-theanine administration suppressed the MIRI-induced decrease of phospho-JAK2 and phospho-STAT3 in ischemic heart tissue. Inhibition of JAK2 by AG490 (5 mg/kg, once daily) abolished the cardioprotective effect of L-theanine, suggesting that the JAK2/STAT3 signaling pathway may play an essential role in mediating the anti-I/R effect of L-theanine. Conclusions L-theanine administration suppresses cellular apoptosis and oxidative stress in part via the JAK2/STAT3 signaling pathway, thereby attenuating MIRI-induced cardiac injury. L-theanine could be developed as a potential drug to alleviate cardiac damage in MIRI.

Abstract Sweet potato stem nematode disease is a devastating disease, which seriously affects the yield and quality of sweet potato (Ipomoea batatas (L.) Lam.). At present, soil treatment with pesticides is mainly used to prevent sweet potato stem nematode disease. In this study, Illumina MiSeq high‐throughput sequencing technology was used to analyze the diversity of soil bacterial and fungal communities treated with different pesticides. At the same time, high performance liquid chromatography was used to determine the pesticide residues in soil and sweet potato, and the impact on sweet potato yield was investigated. Kruskal–Wallis test was used to analyze the four α‐diversity indexes of soil under different pesticide treatments, and the differences were not significant (p > 0.05), indicating that there was no significant difference in the diversity and abundance of bacterial and fungal communities in soil under different pesticide treatments. The results of principal coordinate analysis showed that there was no significant difference in bacterial and fungal community structure among different pesticide treatments (p > 0.05). Pesticide residue analysis and yield statistics of sweet potato showed that the residual amount of three kinds of pesticides in sweet potato did not exceed the maximum limit stipulated by the current National Standards for Food safety (GB2763‐2021). When 5% chlorpyrifos phoxim particles were applied at 15.18 kg/acre, sweet potato was unaffected by pests and diseases basically, and the yield was the highest.

Sinomenine (SIN), an alkaloid extracted from the root of S. acutum. sinomenine, has been shown to have antiarrhythmic, antioxidant, and anti-inflammatory effects in myocardial ischemia-reperfusion injury (MIRI) ex vivo. In this study, we investigated the cardioprotective effects of SIN in an in vivo mouse model of MIRI. Adult male C57BL/6J mice received SIN (80 mg/kg) for 5 days and underwent 30 min of percutaneous occlusion of the left anterior descending artery (LAD) followed by 24 h of reperfusion. Results showed that pretreatment with SIN significantly reduced myocardial infarct size and concentrations of markers of cardiac injury and improved left ventricular ejection fraction (EF) and shortening fraction (FS) in MIRI mice. The SIN pretreatment prevented the MIRI-induced decrease in the expression levels of Bcl-2, increase in the expression levels of caspase-3, caspase-9, and Bax, and increase in the number of TUNEL-positive cells in ischemic heart tissue. It was also found that pretreatment with SIN prevented the MIRI-induced oxidative stress imbalance in ischemic heart tissue, as shown by the increase in total antioxidant capacity (T-AOC) and glutathione (GSH) and the decrease in malondialdehyde (MDA), reactive oxygen species (ROS), and dihydroethidium (DHE) density. Further studies showed that the stimulus of cardiac ischemia/reperfusion caused a remarkable increase in the expression levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) mRNA in ischemic heart tissue, which was effectively prevented by pretreatment with SIN. These results demonstrate that SIN can attenuate MIRI-induced cardiac injury in vivo by preventing oxidative stress, inflammation, and apoptosis.

Strategies for treating myocardial ischemia in the clinic usually include re-canalization of the coronary arteries to restore blood supply to the myocardium. However, myocardial reperfusion insult often leads to oxidative stress and inflammation, which in turn leads to apoptosis and necrosis of myocardial cells, for which there are no standard treatment methods. The aim of this study was to determine the pharmacological effect of indole-3-carbinol (I3C), a phytochemical found in most cruciferous vegetables, in a mouse model of myocardial ischemia/reperfusion injury (MIRI). Our results showed that I3C pretreatment (100 mg/kg, once daily, i. p.) prevented the MIRI-induced increase in infarct size and serum creatine kinase (CK) and lactate dehydrogenase (LDH) in mice. I3C pretreatment also suppressed cardiac apoptosis in MIRI mice by increasing the expression levels of the anti-apoptotic protein Bcl-2 and decreasing the expression levels of several apoptotic proteins, including Bax, caspase-3, and caspase-9. In addition, I3C pretreatment was found to reduce the levels of parameters reflecting oxidative stress, such as dihydroethidium (DHE), malondialdehyde (MDA), reactive oxygen species (ROS), and nitric oxide (NO), while increasing the levels of parameters reflecting anti-oxidation, such as total antioxidant capacity (T-AOC) and glutathione (GSH), in MIRI-induced ischemic heart tissue. I3C pretreatment was also able to remarkably decrease the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) mRNA in ischemic heart tissue. These results demonstrate that administration of I3C protects the heart from MIRI through its anti-apoptotic, antioxidant, and anti-inflammatory effects.

Abstract Objective The primary objective of this clinical trial is to investigate the effect of low-intensity pulsed ultrasound (LIPUS) on patients suffering from comorbid erectile dysfunction (ED) and chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS). Methods The clinical trial was conducted in the andrology outpatient treatment room of the Department of Urology, Xiangya Hospital, Central South University from August to November 2022 A total of 60 patients who met the research criteria for comorbid ED combined with CP/CPPS were recruited and randomly assigned to three treatment groups. They were treated with LIPUS (Group A), drug therapy(Group B), and LIPUS combined with drug therapy (Group C), respectively. Each group comprised 20 patients. Statistical analysis was performed on the five-item version of International Index of Erectile Function (IIEF-5), Erection Hardness Score (EHS), National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), the nine-item Patient Health Questionnaire (PHQ-9), the seven-item Generalized Anxiety Disorder Scale (GAD-7), and the incidence of adverse events to comprehensively evaluate the efficacy and safety of LIPUS. Results The positive response rate of ED and CP/CPPS treatment in Group A is 40%(8/20) and 45%(9/20), while those in Group B is 55%(11/20) and 60%(12/20), and those in Group C is 85%(17/20) and 85%(17/20). A notable increase in IIEF-5 scores was observed across the three groups post-treatment (10.45 ± 2.50 vs. 13.65 ± 3.03, P = 0.008; 11.80 ± 3.21 vs. 16.40 ± 3.20, P = 0.011; 12.90 ± 3.92 vs. 19.40 ± 2.35, P = 0.042) with a concomitant significant decrease in NIH-CPSI scores (16.75 ± 4.53 vs. 14.65 ± 4.51, P = 0.016; 16.35 ± 4.32 vs. 12.20 ± 4.74, P = 0.007; 16.00 ± 4.40 vs. 8.15 ± 4.28, P = 0.021). Notably, the most pronounced changes were seen in the group receiving LIPUS combined with tadalafil and doxazosin. Additionally, all groups exhibited marked improvements in anxiety and depression symptoms post-treatment. No adverse events were observed during treatment. Conclusion LIPUS can improve erectile function and CP/CPPS symptoms with good safety, and LIPUS combined with tadalafil and doxazosin is more effective during the treatment. However, its long-term efficacy remains to be seen. Trial Registration Chinese Clinical Trial Registry; approval number: ChiCTR2200063038 ( https://www.chictr.org.cn/ ) on August 29, 2022.

Abstract Background Starch is a very abundant and renewable carbohydrate and an important feedstock for industrial applications. However, most starch-based products are not cost-efficient due to the high energy input needed in traditional enzymatic starch conversion processes. Raw-starch-digesting enzymes (RSDEs) from filamentous fungi have great commercial value in starch processing. However, the regulatory mechanisms associated with their production in filamentous fungi remain unknown. Results In this study, we reported the novel finding that cellulolytic fungus Penicillium oxalicum 114-2 has broad RSDE activity. Four regulators, including the amylase transcription activator AmyR, the catabolite repression repressor CreA, the group III G protein α subunit PGA3, and the nonhistone chromosomal protein HepA, have been found to play a crucial regulatory role in RSDE expression. Enzymatic assays revealed that RSDE production significantly increased after the overexpression of AmyR and HepA, the deletion of CreA and the dominant activation of PGA3. RT-qPCR analysis demonstrated that there is a mutual regulation mode between the four regulators, and then formed a cascade regulation mechanism that is involved in RSDE expression. Comparative transcriptomic analysis between the wild-type strain and genetically engineered strains revealed differentially expressed genes that may mediate the RSDE expression. Conclusions The four different types of regulators were systematically investigated and found to form a regulatory network controlling RSDE gene expression. Our results provide a new insight into the regulatory mechanism of fungal amylolytic enzyme expression and offer a theoretical basis to rationally improve the RSDE yield in the future.

Abstract Background Filamentous fungi have long been used as hosts for the production of proteins, enzymes and valuable products in various biotechnological applications. However, recombinant proteins are expressed with highly secreted host proteins when stronger promoters are used under inducing conditions. In addition, the efficiency of target protein expression can be limited by the application of constitutive promoters in recently developed filamentous fungal expression systems. Results In this study, a novel expression system was constructed by using a Penicillium oxalium strain that has powerful protein secretion capability. The secretory background of the host was reduced by knocking out the Amy13A protein and utilizing the starch as a carbon source. The strong promoter amy15A(p) was further improved by overexpressing the transcription activator AmyR and deleting of putative repressor CreA. By using the native amylase Amy15A as a reporter, the efficiency of expression from the amy15A promoter was dramatically and specifically enhanced after redesigning the regulatory network of amylase expression. Conclusions Our researches clearly indicated that the triple-gene recombinant strain Δ13A-OamyR-ΔCreA, with the amy15A(p) promoter could be used as a suitable expression system especially for high-level and high-purity protein production.