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Intracerebral hemorrhage (ICH) is a prevalent hemorrhagic cerebrovascular emergency. Alleviating neurological damage in the early stages of ICH is critical for enhancing patient prognosis and survival rate. A novel form of cell death called ferroptosis is intimately linked to hemorrhage-induced brain tissue injury. Although studies have demonstrated the significant preventive impact of bovine serum albumin-stabilized selenium nanoparticles (BSA-SeNPs) against disorders connected to the neurological system, the neuroprotective effect on the hemorrhage stroke and the mechanism remain unknown. Therefore, based on the favorable biocompatibility of BSA-SeNPs, h-ICH (hippocampus-intracerebral hemorrhage) model was constructed to perform BSA-SeNPs therapy. As expected, these BSA-SeNPs could effectively improve the cognitive deficits and ameliorate the damage of hippocampal neuron. Furthermore, BSA-SeNPs reverse the morphology of mitochondria and enhanced the mitochondrial function, evidenced by mitochondrial respiration function (OCR) and mitochondrial membrane potential (MMP). Mechanistically, BSA-SeNPs could efficiently activate the Nrf2 to enhance the expression of antioxidant GPX4 at mRNA and protein levels, and further inhibit lipid peroxidation production in erastin-induced ferroptotic damages. Taken together, this study not only sheds light on the clinical application of BSA-SeNPs, but also provides its newly theoretical support for the strategy of the intervention and treatment of neurological impairment following ICH., Competing Interests: Declaration of competing interest All authors declare that there are no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Previous research has found that an adaptive response to ferroptosis involving glutathione peroxidase 4 (GPX4) is triggered after intracerebral hemorrhage. However, little is known about the mechanisms underlying adaptive responses to ferroptosis. To explore the mechanisms underlying adaptive responses to ferroptosis after intracerebral hemorrhage, we used hemin-treated HT22 cells to mimic brain injury after hemorrhagic stroke in vitro to evaluate the antioxidant enzymes and performed bioinformatics analysis based on the mRNA sequencing data. Further, we determined the expression of GSTO2 in hemin-treated hippocampal neurons and in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH) by using Western blot. After hemin treatment, the antioxidant enzymes GPX4, Nrf2, and glutathione (GSH) were upregulated, suggesting that an adaptive response to ferroptosis was triggered. Furthermore, we performed mRNA sequencing to explore the underlying mechanism, and the results showed that 2234 genes were differentially expressed. Among these, ten genes related to ferroptosis (Acsl1, Ftl1, Gclc, Gclm, Hmox1, Map1lc3b, Slc7a11, Slc40a1, Tfrc, and Slc39a14) were altered after hemin treatment. In addition, analysis of the data retrieved from the GO database for the ten targeted genes showed that 20 items on biological processes, 17 items on cellular components, and 19 items on molecular functions were significantly enriched. Based on the GO data, we performed GSEA and found that the glutathione metabolic process was significantly enriched in the hemin phenotype. Notably, the expression of glutathione S-transferase omega (GSTO2), which is involved in glutathione metabolism, was decreased after hemin treatment, and overexpression of Gsto2 decreased lipid reactive oxygen species level in hemin-exposed HT22 cells. In addition, the expression of GSTO2 was also decreased in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH). The decreased expression of GSTO2 in the glutathione metabolic process may be involved in ferroptotic neuronal injury following hemorrhagic stroke., (© 2024. The Author(s).)

Objective: To analyze the epidemiological characteristics of the cases firstly reported as "asymptomatic infection of COVID-19" in Guangdong province. Methods: The follow-up observation method was used to continuously track and observe the cases firstly reported as "asymptomatic patients with COVID-19" in Guangdong province from January 14 to March 31, 2020. The epidemiological data of the cases were collected to analyze their epidemiological characteristics, outcome and influencing factors. Results: From January 14 to March 31, 2020, a total of 325 cases were firstly reported as "asymptomatic infections of COVID-19" in Guangdong province. The epidemic curve of asymptomatic infection cases was similar to that of confirmed cases, and it had two peaks. The first peak was from January 27 to February 5, and the second peak was from March 17 to March 26. Of the 325 cases, 184 (56.6%) were subsequently converted to confirmed cases. These cases were defined as incubation period asymptomatic infection cases. The age median of the cases was 40 years, and 93.5% (172/184) of the cases showed symptoms within 3 days after the first positive nucleic acid tests were conducted, and 141 (43.4%) of the 325 cases remained asymptomatic status until they were cured and discharged. They were inapparent infection cases, accounting for 8.6% (141/1 642) of those diagnosed with COVID-19 in Guangdong province during the same period. The age median of inapparent infection cases was 27 years. The median of the interval between the first positive nucleic acid test and discharge was 14 days. Up to 90.8% (138/141) of the inapparent infection cases were discharged for centralized medical observation within 28 days. The longest interval between the first positive nucleic acid test and the last positive nucleic acid test was 73 days. The positive rate of nucleic acid test was 0.3% in close contacts of inapparent infection cases and 2.2% in close contacts of incubation period asymptomatic infection cases. There were significant differences in age distribution and source of infection between incubation period asymptomatic infection cases and inapparent infection cases ( P <0.05). Old age was the risk factor for the conversion of firstly reported asymptomatic infection cases to confirmed cases. Compared with the 0-19-year-old group, The patients aged 40-59 years and 60 years and above were more likely to become confirmed cases. The OR (95 %CI ) values were 2.730 (1.380-5.402) and 5.302 (2.199-12.783), and P values were 0.004 and 0.000, respectively. People being infected in China were more likely to become confirmed cases ( OR =7.121, P =0.000). Conclusions: There were asymptomatic infection cases among patients diagnosed with COVID-19. The infectiousness of incubation period asymptomatic infection cases might be stronger than that of inapparent infection cases. The proportion of younger cases among asymptomatic infection cases was higher than that of the confirmed cases. Old age and domestic infection were the risk factors for the conversion of asymptomatic infection cases to confirmed cases, to which more attention should be paid. Further serological investigations are needed to provide a basis for the development of COVID-19 prevention and control strategies.

Ralstonia solanacearum is an extremely destructive and rebellious phytopathogen that can cause bacterial wilt diseases in more than 200 plant species. To explore and discover the potential targets in R. solanacearum for the purpose of developing new agrochemicals targeting this infection, here, we exploited a typical activity-based protein profiling technique for target discovery in R. solanacearum based on an activity-based probe 1 derived from bioactive oxadiazole sulfones. A total of 65 specific targets were identified with high confidence through a quantitative chemical proteomic approach. Three representative proteins (glycine cleavage system H protein, thiol peroxidase, and dihydrolipoamide S -succinyltransferase) were validated as the targets by using the immunoblotting analysis with their respective antibodies. Additionally, the in vitro interaction between the recombinant thiol peroxidase and probe 1 further confirmed that this protein was a target of oxadiazole sulfones. We anticipated that these discovered protein targets in R. solanacearum can stimulate the discovery and development of novel agrochemicals targeting bacterial infections caused by R. solanacearum .

Legionella pneumophila , an environmental bacterium that parasitizes protozoa, is the causative pathogen of Legionnaires' disease. L. pneumophila adopts a distinct biphasic life cycle that allows it to adapt to environmental conditions for survival, replication, and transmission. This cycle consists of a non-virulent replicative phase (RP) and a virulent transmissive phase (TP). Timely and fine-tuned expression of growth and virulence factors in a life cycle-dependent manner is crucial. Herein, we report evidence that CsrA, a key regulator of the switch between the RP and the TP, is dually regulated in a ClpP-dependent manner during the biphasic life cycle of L. pneumophila . First, we show that the protein level of CsrA is temporal during the life cycle and is degraded by ClpP during the TP. The ectopic expression of CsrA in a Δ clpP mutant, but not in the wild type, inhibits both the initiation of the RP in vitro and the invasiveness to Acanthamoeba castellanii , indicating that the ClpP-mediated proteolytic pathway regulates the CsrA protein level. We further show that the temporally expressed IHFB is the transcriptional inhibitor of csrA and is degraded via a ClpP-dependent manner during the RP. During the RP, the level of CsrA is increased by promoting the degradation of IHFB and reducing the degradation of the accumulated CsrA via a ClpP-dependent manner. During the TP, the level of CsrA is decreased by inhibiting the degradation of IHFB and promoting the degradation of the accumulated CsrA via a ClpP-dependent manner as well. In conclusion, our results show that the growth-stage-specific expression level of CsrA is dually regulated by ClpP-dependent proteolysis at both the transcription and protein levels during the biphasic life cycle of L. pneumophila ., (Copyright © 2019 Ge, Long, Yuan, Pan, Shen and Lu.)

The limited number of agrochemicals targeting plant bacterial diseases has driven us to develop highly efficient, low-cost, and versatile antibacterial alternatives. Herein, a novel type of simple furan-functionalized quinazolin-4-amines was systematically fabricated and screened for their antibacterial activity. Bioassay results revealed that compounds C 1 and E 4 could substantially block the growth of two frequently mentioned pathogens Xanthomonas oryzae pv oryzae and X. axonopodis pv citri in vitro, displaying appreciable EC 50 values of 7.13 and 10.3 mg/L, respectively. This effect was prominently improved by comparing those of mainly used agrochemicals. An in vivo experiment against bacterial blight further illustrated their viable applications as antimicrobial ingredients. Quantitative proteomics demonstrated that C 1 possessed a remarkable ability to manipulate the upregulation and downregulation of expressed proteins, which probably involved d-glucose and biotin metabolic pathways. This finding was substantially verified by parallel reaction monitoring analysis. Scanning electron microscopy images and fluorescence spectra also indicated that the designed compounds had versatile capacities for destroying the integrity of bacteria. Given these remarkable characteristics, furan-functionalized quinazoline hybrids can serve as a viable platform for developing innovative antibiotic alternatives against bacterial infections.

The influence of reward on behavior is one of the hottest research subjects in psychological research. Reward-induced motivation promotes the performance of the participants. In the field of emotional processing, the reward can influence the individual's processing of emotional information, but previous studies have not directly discussed the effect of reward on emotional regulation. The present study focused on whether emotional regulation ability would be improved under the reward condition. Experiment 1 and 2 investigated the effect of reward on negative emotional down-regulation and positive emotional up-regulation respectively. In experiment 1, monetary reward stimulation was introduced on the basis of the classic emotion regulation paradigm, and the subjects were asked to regulate their negative emotion under the condition of reward or non-reward, and evaluate their current affective state subsequently. Similar to experiment 1, experiment 2 required subjects to up-regulate positive emotions under the condition of reward or non-reward. The results of experiment 1 showed that under the reward condition, the negative emotional regulation effect was significantly higher than that under the non-reward condition (P < 0.05). Experiment 2 also showed that compared to non-reward condition, the positive emotion regulation effect was significantly increased under the reward condition (P < 0.05). These results suggested that compared to non-reward condition, participants can regulate their emotion better under the condition of the reward. It is worth noting that the results of Experiment 1 and 2 may be caused by the incentive motivation induced by monetary stimulus, or the positive emotion caused by positive value of money information. Therefore, we carried out experiment 3 and 4 to explore whether the positive emotions induced by money itself can influence the emotional regulation of individuals. In experiment 3, the money pictures were used to induce the positive emotions of subjects, and the subjects were asked to regulate their negative emotion after the presence of money pictures or non-monetary picture, and evaluate their current affective state subsequently. Similarly, experiment 4 required subjects to regulate their positive emotion after the presence of money pictures. The results of experiment 3 and 4 showed that there was no significant difference in the subjects' scores of emotional pleasantness after the presence of money pictures or non-monetary picture (P < 0.05). The results of experiment 3 and 4 excluded the possibility that the positive emotions induced by simple money stimulus pictures could improve individual's emotional regulation ability. To sum up, the improvement of individual's emotional regulation ability was indeed driven by reward motivation in this study, that is, the motivation induced by reward can effectively promote individual's emotional regulation ability.

A novel series of simple 1,3,4-oxadiazoles that bear flexible heterocyclic patterns was prepared, and their biological activities in plant pathogenic bacteria, fungi, oomycetes, and Meloidogyne incognita in vitro and in vivo were screened to explore low-cost and versatile antimicrobial agents. Screening results showed that compounds, such as A 0 , B 0 , and C 4 , were bioactive against Xanthomonas oryzae pv oryzae in vitro and in vivo , and such bioactivities were superior to those of commercial agents bismerthiazol and thiodiazole copper. Their antibacterial mechanisms were further investigated by quantitative proteomics and concentration-dependent scanning electron microscopy images. Antifungal results indicated that compound A 0 displayed a selective and better antifungal effect on Botrytis cinerea with inhibition rate of 96.8% at 50 μg/mL. Nematocidal bioassays suggested that compound D 1 had good in vitro nematocidal activity toward M. incognita at 24, 48, and 72 h, with the corresponding insecticidal efficiency of 48.7%, 64.1%, and 87.2% at 40 μg/mL. In vivo study further confirmed that compounds D 1 and F 2 showed nematocidal actions at 80 μg/mL with a disease index of 1.5. Given these advantages, this kind of molecular frameworks could be a suitable platform for exploring highly efficient agrochemicals.

Recent observations on the emergence of drug-resistant plant pathogenic bacteria have highlighted and elicited an acute campaign to develop novel, highly efficient antibiotic surrogates for managing bacterial diseases in agriculture. Thus, a type of racemic and chiral carbazole derivative containing an isopropanolamine pattern was systematically synthesized to discover low-cost and efficient antibacterial candidates. Screening results showed that compounds 2f, 6c, and 2j could significantly suppress the growth of tested plant pathogens, namely Xanthomonas oryzae pv oryzae, X. axonopodis pv citri, and Pseudomonas syringae pv actinidiae, and provided the corresponding EC 50 values of 1.27, 0.993, and 0.603 μg/mL, which were significantly better than those of existing commercial drugs. In vivo studies confirmed their prospective applications for controlling plant bacterial diseases. Label-free quantitative proteomics analysis indicated that compound 2f could dramatically induce the up- and down-regulation of a total of 247 differentially expressed proteins, which was further validated by the parallel reaction monitoring technique. Moreover, fluorescence spectra and SEM images were obtained to further explore the antibacterial mechanism.

Photoaffinity labeling (PAL) in combination with a chemical probe to covalently bind its target upon UV irradiation has demonstrated considerable promise in drug discovery for identifying new drug targets and binding sites. In particular, carbene-mediated photoaffinity labeling (cmPAL) has been widely used in drug target identification owing to its excellent photolabeling efficiency, minimal steric interference and longer excitation wavelength. Specifically, diazirines, which are among the precursors of carbenes and have higher carbene yields and greater chemical stability than diazo compounds, have proved to be valuable photolabile reagents in a diverse range of biological systems. This review highlights current advances of cmPAL in medicinal chemistry, with a focus on structures and applications for identifying small molecule-protein and macromolecule-protein interactions and ligand-gated ion channels, coupled with advances in the discovery of targets and inhibitors using carbene precursor-based biological probes developed in recent decades., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Peptide aptamers are molecules which can specifically bind to a given target protein and have the potential to selectively block the function of the target protein. It has been reported that a peptide aptamer (C1-1) identified from a randomized expression library specifically bound to the core protein of hepatitis B virus and inhibited viral capsid formation and DNA replication in vitro. Adenoviral systems are popular platforms for reliable gene delivery and high-level transient expression in any mammalian cell type in vitro, and have a natural tropism for the liver after systemic administration. In the present study, we explored the feasibility of gene therapy against HBV infection with adenoviral system, and found that systematic administration of recombinant adenovirus encoding the peptide aptamer (C1-1) significantly inhibited viral capsid formation, HBV DNA replication and virion production in vivo. These results suggest an efficient antiviral treatment against HBV infection by delivery of anti-HBV peptide aptamer with recombinant adenovirus.