Early diagnosis and staging of paraquat-induced pulmonary fibrosis using [18F]F-FAPI-42 PET/CT imaging.

BACKGROUND: Paraquat (PQ) -induced pulmonary fibrosis poses a significant medical challenge due to limited treatment options and high mortality rates. Consequently, there is an urgent need for early diagnosis and accurate staging to facilitate appropriate treatment strategies. In this study, we assessed the diagnostic potential of [18F]F-FAPI-42 PET/CT imaging for early detection and disease staging in a rat model of PQ-induced lung fibrosis. METHODS: After administering 80 mg/kg of PQ orally to Sprague-Dawley rats, we intravenously injected 3-3.5 MBq of [18F]F-FAPI-42 on day 7, 14, and 21 post-dosing. Dynamic PET/CT imaging was carried out for one hour immediately after the administration of [18F]F-FAPI-42. Subsequently, the lung tissues were collected for Hematoxylin and Eosin (HE) staining, Masson's trichrome staining, and NOTA-FAPI-04-MB fluorescent probe staining. Data analysis was performed using the Imalytics preclinical software, and the mean standardized uptake value (SUVmean) was calculated. RESULTS: PET signals revealed that in areas with evident lesions on CT, the SUVmean on day 14 was significantly higher than on day 7 and 21, indicating that changes in fibrosis activity levels contribute to the staging of pulmonary fibrosis. Additionally, the NOTA-FAPI-04-MB fluorescent probe staining also demonstrated the most pronounced probe uptake on day 14. In regions without apparent lesions on CT, the SUVmean gradually increased from day 7 to day 21, reflecting ongoing fibrotic activity. Moreover, HE staining and Masson's trichrome staining did not reveal pulmonary fibrosis, while PET imaging was able to detect it, serving the purpose of early diagnosis. At 30 min and 60 min, the target-to-background ratio (TBR) of the PQ groups on day 7, 14, and 21 was significantly higher than the control group, suggesting a high specificity of [18F]F-FAPI-42 binding to activated fibroblasts. CONCLUSION: [18F]F-FAPI-42 PET/CT imaging enables early diagnosis and staging of PQ-induced pulmonary fibrosis, demonstrating its feasibility and potential for characterizing early disease stages.

Therapeutic effects of vitamin D supplementation on COVID-19 aggravation: a systematic review and meta-analysis of randomized controlled trials.

Background: The therapeutic effects of vitamin D supplementation on Coronavirus disease 2019 (COVID-19) aggravation remain controversial and inconclusive. To probe into this contentious issue, we performed the present meta-analysis of randomized controlled trials (RCTs). Methods: Literature published up to June 2023 was retrieved from Cochrane Library, PubMed, Web of Science and Embase. RCTs assessing mortality, intensive care unit (ICU) admission, mechanical ventilation (MV), length of hospitalization (LOH), and inflammatory markers containing C-reactive protein (CRP), D-dimer, interleukin-6 (IL-6), lactate dehydrogenase (LDH) were included. 19 RCTs were involved in the analysis and were conducted subgroup analyses on the baseline COVID-19 severity and vitamin D administration. Results: In the severity subgroup, statistically significant effects in moderate to severe group were observed in ICU admission (OR 0.43, 95% CI 0.23, 0.80; p = 0.008), MV (OR 0.44, 95% CI 0.27, 0.72; p = 0.001) and LOH (SMD -0.49, 95% CI -0.92, -0.06; p = 0.027). In the administration subgroup, effects of ICU admission (OR 0.39, 95% CI 0.16, 0.97; p = 0.044), MV (OR 0.18, 95% CI 0.07, 0.46; p = 0.000) and LOH (SMD -0.50, 95% CI -0.96, -0.04; p = 0.034) were more pronounced in patients supplied with multiple-dose vitamin D than single-dose. Although the result of mortality showed no statistically significant effect, it indicated a reduced trend (OR 0.87, 95% CI 0.63, 1.12; p > 0.05). The results of inflammatory markers reached no statistical differences. Conclusion: This meta-analysis revealed that moderate to severe COVID-19 patients supplied with multiple doses of vitamin D were less apt to need ICU admission, mechanical ventilation and have shorter hospital stays.

Brassinosteroid-dependent phosphorylation of PHOSPHATE STARVATION RESPONSE2 reduces its DNA-binding ability in rice.

Brassinosteroids (BRs) are widely used as plant growth regulators in modern agriculture. Understanding how BRs regulate nutrient signaling is crucial for reducing fertilizer usage. Here we elucidate that the central BR signaling inhibitor GSK3/SHAGGY-LIKE KINASE2 (GSK2) interacts directly with and phosphorylates PHOSPHATE STARVATION RESPONSE2 (OsPHR2), the key regulator of phosphate (Pi) signaling, to suppress its transcription factor activity in rice (Oryza sativa). We identify a critical phosphorylation site at serine residue S269 of OsPHR2 and demonstrate that phosphorylation by GSK2 or phosphor-mimic mutation of S269 substantially impairs the DNA-binding activity of OsPHR2, and thus diminishes expression of OsPHR2-induced genes and reduces Pi levels. Like BRs, Pi starvation noticeably induces GSK2 instability. We further show that this site-specific phosphorylation event is conserved in Arabidopsis (Arabidopsis thaliana), but varies among the PHR-family members, being present only in most land plants. These results unveil a distinctive post-transcriptional regulatory mechanism in Pi signaling by which BRs promote Pi acquisition, with a potential contribution to the environmental adaptability of plants during their evolution.

Overall and individual associations between per- and polyfluoroalkyl substances and liver function indices and the metabolic mechanism.

Per- and polyfluoroalkyl substances (PFAS) can disrupt liver homeostasis. Studies have shown that a single exposure to PFAS may provoke abnormal liver function; however, few studies have investigated the overall effect of PFAS mixtures. We aimed to investigate associations between exposure to PFAS mixtures and liver function indices and explore the relevant mechanisms. This study included 278 adult males from Guangzhou, China. Serum metabolite profiles were analyzed using untargeted metabolomics. We applied weighted quantile sum (WQS) regression as well as Bayesian kernel machine regression (BKMR) to analyze the association of nine PFAS mixtures with 14 liver function indices. PFAS mixtures were positively associated with apolipoprotein B (APOB) and gamma-glutamyltransferase (GGT) and negatively associated with direct bilirubin (DBIL) and total bilirubin (TBIL) in both the WQS and BKMR analyses. In addition, Spearman's correlation test showed individual PFAS correlated with APOB, GGT, TBIL, and DBIL, while there's little correlation between individual PFAS and other liver function indices. In linear regression analysis, PFHxS, PFOS, PFHpS, PFNA, PFDA, and PFUdA were associated with APOB; PFOA, PFDA, PFOS, PFNA, and PFUdA were associated with GGT. Subsequently, a metabolome-wide association study and mediation analysis were combined to explore metabolites that mediate these associations. The mechanisms linking PFAS to APOB and GGT are mainly related with amino acid and glycerophospholipid metabolism. High-dimensional mediation analysis showed that glycerophospholipids are the main markers of the association between PFAS and APOB, and that (R)-dihydromaleimide, Ile Leu, (R)-(+)-2-pyrrolidone-5-carboxylic acid, and L-glutamate are the main markers of the association between PFAS and GGT. In summary, overall associations between PFAS and specific indices of liver function were found using two statistical methods; the metabolic pathways and markers identified here may serve to prompt more detailed study in animal-based systems, as well as a similar detailed analysis in other populations.

Seasonal variations of airborne microbial diversity in waste transfer stations and preventive effect on Streptococcus pneumoniae induced pulmonary inflammation.

Environment, location, and season are important factors that influence the microbiological community, yet, little research on airborne microorganisms in waste transfer stations (WTSs). Here, the airborne bacterial and fungal communities at four WTSs during different seasons were analyzed by high-throughput sequencing. The bacteria were isolated by cultural method and screened bacterium alleviate inflammation induced by Streptococcus pneumoniae (Spn) by regulating gut microbiome. The results revealed that collected bioaerosols from the WTSs varied significantly by location and season. Proteobacteria and Pseudomonadota are prevalent in summer and winter, respectively. Ascomycota was predominant in two seasons. Hazard quotients for adults from four WTSs were below one. Three selected potential probiotics were formulated into a microbial preparation with a carrier that effectively prevented inflammation in bacterial and animal experiments. The expression levels of interleukin-1ß, interleukin-6, and tumor necrosis factor-α in Pre group (0.11, 0.17, and 0.48-fold) were significantly lower than Spn group (2.75, 1.71, and 5.01-fold). These mechanisms are associated with changes in gut microbiota composition and short-chain fatty acids (SCFAs) levels, such as affecting Lachnospiraceae lachnospira abundance and acetic acid content. This study provides insights into the potential application of probiotics derived from WTSs as an alternative approach to preventing respiratory infections.

Effects of tris (2-chloroethyl) phosphate exposure on gut microbiome using the simulator of the human intestinal microbial ecosystem (SHIME).

Tris (2-chloroethyl) phosphate (TCEP) has been widely used, and its health risk has received increasing attention. However, the rare research has been conducted on the effects of TCEP exposure on changes in the structure of the human gut microbiome and metabolic functions. In this experiment, Simulator of the human intestinal microbial ecosystem (SHIME) was applied to explore the influences of TCEP on the human gut bacteria community and structure. The results obtained from high-throughput sequencing of 16S rRNA gene have clearly revealed differences among control and exposure groups. High-dose TCEP exposure increased the Shannon and Simpson indexes in the results of α-diversity of the gut microbiome. At phylum level, Firmicutes occupied a higher proportion of gut microbiota, while the proportion of Bacteroidetes decreased. In the genus-level analysis, the relative abundance of Bacteroides descended with the TCEP exposure dose increased in the ascending colon, while the abundances of Roseburia, Lachnospira, Coprococcus and Lachnoclostridium were obviously correlated with exposure dose in each colon. The results of short chain fatty acids (SCFAs) showed a remarkable effect on the distribution after TCEP exposure. In the ascending colon, the control group had the highest acetate concentration (1.666 ± 0.085 mg⋅mL-1), while acetate concentrations in lose-dose medium-dose and high-doseTCEP exposure groups were 1.119 ± 0.084 mg⋅mL-1, 0.437 ± 0.053 mg⋅mL-1 and 0.548 ± 0.106 mg⋅mL-1, respectively. TCEP exposure resulted in a decrease in acetate and propionate concentrations, while increasing butyrate concentrations in each colon. Dorea, Fusicatenibacter, Kineothrix, Lachnospira, and Roseburia showed an increasing tendency in abundance under TCEP exposure, while they had a negatively correlation with acetate and propionate concentrations and positively related with butyrate concentrations. Overall, this study confirms that TCEP exposure alters both the composition and metabolic function of intestinal microbial communities, to arouse public concern about its negative health effects.

Roseicella aerolata GB24T from bioaerosol attenuates Streptococcus pneumoniae-introduced inflammation through regulation of gut microbiota and acetic acid.

Streptococcus pneumoniae (Spn) is the most common respiratory pathogen causing community-acquired pneumonia. Probiotics represent a new intervention target for Spn infection. Hence, the discovery and development of new potential probiotic strains are urgently needed. This study was designed to investigate the beneficial effect and mechanism of a new bacterium named Roseicella aerolata GB24T that antagonizes Spn at cellular and animal levels. The results revealed that GB24T strain inhibited the growth of Spn on sheep blood agar plates, forming inhibition circles with a diameter of 20 mm. In cultured bronchial epithelium transformed with Ad 12-SV40 2B (BEAS-2B) cells, Spn infection induced an elevation in the expression levels of interleukin-1ß, interleukin-6, and tumor necrosis factor-α to 4.289 ± 0.709, 5.587 ± 2.670, and 5.212 ± 0.772 folds compared to healthy controls, respectively. Moreover, pre-infection with GB24T for 1.5 h almost eliminated the cellular inflammation caused by Spn infection. Additionally, male Sprague-Dawley rats infected with Spn were randomly allocated into two groups: GB24T pre-infection and Spn infection groups, with healthy rats as control. GB24T significantly alleviated inflammatory lung injury caused by Spn infection, which was associated with obvious changes in the abundance of gut microbiota and a trend toward enhanced secretion of short-chain fatty acids, especially acetic acid. Acetic acid was validated to be effective in alleviating inflammation due to Spn infection in cellular assays. Together, these findings highlight that GB24T strain is an important protective feature in the respiratory tract.

Maternal transfer of resorcinol-bis(diphenyl)-phosphate perturbs gut microbiota development and gut metabolism of offspring in rats.

Resorcinol-bis(diphenyl)-phosphate (RDP), an emerging organophosphate flame retardant, is increasingly used as a primary alternative for decabromodiphenyl ether and is frequently detected in global environmental matrices. However, the long-term effects of its exposure to humans remain largely unknown. To investigate its intergenerational transfer capacity and health risks, female Sprague Dawley rats were orally exposed to RDP from the beginning of pregnancy to the end of the lactation period. The RDP content, gut microbiota homeostasis, and metabolic levels were determined. RDP accumulation occurred in the livers of maternal rats and offspring and increased with exposure time. 16S rRNA gene sequencing showed that exposure to RDP during pregnancy and/or lactation significantly disrupted gut microbiota homeostasis, as evidenced by decreased abundance and diversity. In particular, the abundance of Turicibacter, Adlercreutzia, and YRC22 decreased, correlating significantly with glycollipic metabolism. This finding was consistent with the reduced levels of short-chain fatty acids, the crucial gut microbial metabolites. Meanwhile, RDP exposure resulted in changes in gut microbiome-related metabolism. Nine critical overlapping KEGG metabolic pathways were identified, and the levels of related differential metabolites decreased. Our results suggest that the significant adverse impacts of RDP on gut microbiota homeostasis and metabolic function may increase the long-term risks related to inflammation, obesity, and metabolic diseases.

Crosstalk between brassinosteroid signaling and variable nutrient environments.

Brassinosteroid (BR) represents a group of steroid hormones that regulate plant growth and development as well as environmental adaptation. The fluctuation of external nutrient elements is a situation that plants frequently face in the natural environment, in which nitrogen (N) and phosphorus (P) are two of the most critical nutrients restraint of the early growth of plants. As the macronutrients, N and P are highly required by plants, but their availability or solubility in the soil is relatively low. Since iron (Fe) and P always modulate each other's content and function in plants mutually antagonistically, the regulatory mechanisms of Fe and P are inextricably linked. Recently, BR has emerged as a critical regulator in nutrient acquisition and phenotypic plasticity in response to the variable nutrient levels in Arabidopsis and rice. Here, we review the current understanding of the crosstalk between BR and the three major nutrients (N, P, and Fe), highlighting how nutrient signaling regulates BR synthesis and signaling to accommodate plant growth and development in Arabidopsis and rice.

Polybrominated diphenyl ethers and bromophenols in paired serum, hair, and urine samples of e-waste dismantlers: Insights into hair as an indicator of endogenous exposure.

Polybrominated diphenyl ethers (PBDEs) are important pollutants during dismantling activities of electronic waste (e-waste) in China due to its large production and usage. Bromophenols (BPs), which are a kind of flame retardants and diphenyl ether bond cleavage metabolites of PBDEs, are often neglected in the assessment of human exposure to e-waste. Herein, 22 PBDEs and 19 BPs were determined in paired serum, hair, and urine samples collected from workers and residents of a typical e-waste dismantling site in southern China. Both PBDE and BP congeners were more frequently detected in hair than serum and urine samples. The medians of ΣPBDEs and ΣBPs were 350 and 547 ng/g dw in hair internal (hair-In) of occupational population, respectively, which were significantly higher than non-occupational population. However, a non-significant difference was found in levels of ΣPBDEs and ΣBPs in serum and urine between occupational and non-occupational populations, suggesting that hair analysis could easily differentiate between the exposure intensities of PBDEs and BPs to populations than serum and urine analyses. Moreover, levels of BPs in hair-In were 1-2 orders of magnitude higher than those in hair external (hair-Ex), while a non-significant difference was found in the levels of PBDEs. This result indicated that BPs might have originated from endogenous contribution. Notably, as the predominant congeners, the level of 2,4,6-tribromophenol (2,4,6-TBP) in hair-In was 3-8 times higher than that of BDE-209, while level of 2,4,6-TBP in hair-Ex was 1-3 times lower than that of BDE-209. Furthermore, in vivo experiments performed on Sprague-Dawley rats following a 28-day oral treatment with BDE-209 and 2,4,6-TBP verified that endogenous accumulation of 2,4,6-TBP in hair could be attributed to the metabolism of BDE-209 and exposure to 2,4,6-TBP. In conclusion, compared with PBDEs, biomonitoring phenolic compounds or metabolites with hair could better reflect human endogenous exposure.

Associated long-term effects of decabromodiphenyl ethane on the gut microbial profiles and metabolic homeostasis in Sprague-Dawley rat offspring.

Decabromodiphenyl ethane (DBDPE) as a widely used brominated flame retardant is harmful to human health due to its toxicity, including cardiovascular toxicity, reproductive toxicity, and hepatotoxicity. However, the knowledge of the long-term effects and structural and metabolic function influence on gut microbiota from DBDPE exposure remains limited. This study was mainly aimed at the gut microbiome and fecal metabolome of female rats and their offspring exposed to DBDPE in early life. 16S rRNA gene sequencing demonstrated that maternal DBDPE exposure could increase the α-diversity of gut microbiota in immature offspring while decreasing the abundance of Bifidobacterium, Clostridium, Muribaculum, Escherichia, and Lactobacillus in adult offspring. The nonmetric multidimensional scaling showed a consistency in the alternation of ß-diversity between pregnant rats and their adult offspring. Furthermore, the short-chain fatty acids produced by gut microbiota dramatically increased in adult offspring after maternal DBDPE exposure, revealing that DBDPE treatment disrupted the gut microbial compositions and altered the gut community's metabolic functions. Untargeted metabolomics identified 41 differential metabolites and seven metabolic pathways between adult offspring from various groups. Targeted metabolomic showed that maternal high dose DBDPE exposure obviously decreased the level of glutathione, taurine, and l-carnitine in their adult offspring, which verified the correlation between weight loss and amino acid metabolites. An interesting link between some gut bacteria (especially the Firmicutes) and fecal metabolites demonstrated the shifts in gut microbiota may drive the metabolic process of fecal metabolites. The current findings provide new insight into long-term effects on human health.

The U-box ubiquitin ligase TUD1 promotes brassinosteroid-induced GSK2 degradation in rice.

Brassinosteroids (BRs) are a class of steroid hormones with great potential for use in crop improvement. De-repression is usually one of the key events in hormone signaling. However, how the stability of GSK2, the central negative regulator of BR signaling in rice (Oryza sativa), is regulated by BRs remains elusive. Here, we identify the U-box ubiquitin ligase TUD1 as a GSK2-interacting protein by yeast two-hybrid screening. We show that TUD1 is able to directly interact with GSK2 and ubiquitinate the protein. Phenotypes of the tud1 mutant are highly similar to those of plants with constitutively activated GSK2. Consistent with this finding, GSK2 protein accumulates in the tud1 mutant compared with the wild type. In addition, inhibition of BR synthesis promotes GSK2 accumulation and suppresses TUD1 stability. By contrast, BRs can induce GSK2 degradation but promote TUD1 accumulation. Furthermore, the GSK2 degradation process is largely impaired in tud1 in response to BR. In conclusion, our study demonstrates the role of TUD1 in BR-induced GSK2 degradation, thereby advancing our understanding of a critical step in the BR signaling pathway of rice.

RNA modifications in aging-associated cardiovascular diseases.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide that bears an enormous healthcare burden and aging is a major contributing factor to CVDs. Functional gene expression network during aging is regulated by mRNAs transcriptionally and by non-coding RNAs epi-transcriptionally. RNA modifications alter the stability and function of both mRNAs and non-coding RNAs and are involved in differentiation, development, and diseases. Here we review major chemical RNA modifications on mRNAs and non-coding RNAs, including N6-adenosine methylation, N1-adenosine methylation, 5-methylcytidine, pseudouridylation, 2' -O-ribose-methylation, and N7-methylguanosine, in the aging process with an emphasis on cardiovascular aging. We also summarize the currently available methods to detect RNA modifications and the bioinformatic tools to study RNA modifications. More importantly, we discussed the specific implication of the RNA modifications on mRNAs and non-coding RNAs in the pathogenesis of aging-associated CVDs, including atherosclerosis, hypertension, coronary heart diseases, congestive heart failure, atrial fibrillation, peripheral artery disease, venous insufficiency, and stroke.

Understanding the Protective Role of Exosomes in Doxorubicin-Induced Cardiotoxicity.

Doxorubicin (DOX) is a class of effective chemotherapeutic agents widely used in clinical practice. However, its use has been limited by cardiotoxicity. The mechanism of DOX-induced cardiotoxicity (DIC) is complex, involving oxidative stress, Ca2+ overload, inflammation, pyroptosis, ferroptosis, apoptosis, senescence, etc. Exosomes (EXOs), as extracellular vesicles (EVs), play an important role in the material exchange and signal transmission between cells by carrying components such as proteins and RNAs. More recently, there has been a growing number of publications focusing on the protective effect of EXOs on DIC. Here, this review summarized the main mechanisms of DIC, discussed the mechanism of EXOs in the treatment of DIC, and further explored the value of EXOs as diagnostic biomarkers and therapeutic strategies for DIC.

Microcella aerolata sp. nov., isolated from electronic waste-associated bioaerosols.

A Gram-positive, non-motile, non-spore-forming and short rod-shaped actinomycete strain, designated GA224T, was isolated from electronic waste-associated bioaerosols. The optimal growth conditions for this isolate, a facultatively anaerobic bacterium, were 37 °C and pH 8.0. The cell-wall peptidoglycan type was B2γ, with 2,4-diaminobutyric acid (DAB) as the diamino acids, while the major menaquinone was MK-12. The polar lipid profile was composed of diphosphatidylglycerol, phosphatidylglycerol, unidentified phospholipids, unidentified glycolipids and an unidentified lipid. The major cellular fatty acids were anteiso-C15:0 and iso-C16:0. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain GA224T fell within the genus Microcella. The draft genome of strain GA224T comprised 2,495,189 bp with a G + C content of 72.2 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain GA224T and the type strain of the type species of Microcella species were lower than 95% and 70%, respectively. Based on the phenotypic, chemotaxonomic and genomic data, strain GA224T represents a novel species, for which the name Microcella aerolata sp. nov. is proposed, with GA224T as the type strain (= GDMCC 1.2165 T = JCM 34462 T).

The disruption on gut microbiome of Decabromodiphenyl ethane exposure in the simulator of the human intestinal microbial ecosystem (SHIME).

The health risks of Decabromodiphenyl ethane (DBDPE) with its cardiovascular toxicity, liver toxicity and cytotoxicity had been generally acknowledged. However, the influence on gut microbiome and short-chain fatty acids (SCFAs) metabolism caused by DBDPE exposure remained unknown. In this study, three exposure groups (5, 50, 500 mg/L) and control group were used to investigate the effect of DBDPE by using simulator of the human intestinal microbial ecosystem (SHIME). 16S rRNA gene high-throughput sequencing illustrated that high dose DBDPE exposure increased the α-diversity of gut microbiota, while reduced the abundance of Firmicutes and Proteobacteria. In addition, the low dose (5 mg/L) DBDPE inhibited the increasing of SCFAs, but the medium and high dose (50 and 500 mg/L) DBDPE promoted the advancement, especially in ascending colon. Notably, DBDPE exposure lead a similar changing of acetic acid and butyric acid contents in different sections of the colon. This study confirmed the alternation of composition and metabolic function in gut microbial community due to DBDPE exposure, indicating an intestinal damage and appealing for more attention concentrated on the health effects of DBDPE exposure.

The divergence of brassinosteroid sensitivity between rice subspecies involves natural variation conferring altered internal auto-binding of OsBSK2.

Japonica/geng and indica/xian are two major rice (Oryza sativa) subspecies with multiple divergent traits, but how these traits are related and interact within each subspecies remains elusive. Brassinosteroids (BRs) are a class of steroid phytohormones that modulate many important agronomic traits in rice. Here, using different physiological assays, we revealed that japonica rice exhibits an overall lower BR sensitivity than indica. Extensive screening of BR signaling genes led to the identification of a set of genes distributed throughout the primary BR signaling pathway with divergent polymorphisms. Among these, we demonstrate that the C38/T variant in BR Signaling Kinase2 (OsBSK2), causing the amino acid change P13L, plays a central role in mediating differential BR signaling in japonica and indica rice. OsBSK2L13 in indica plays a greater role in BR signaling than OsBSK2P13 in japonica by affecting the auto-binding and protein accumulation of OsBSK2. Finally, we determined that OsBSK2 is involved in a number of divergent traits in japonica relative to indica rice, including grain shape, tiller number, cold adaptation, and nitrogen-use efficiency. Our study suggests that the natural variation in OsBSK2 plays a key role in the divergence of BR signaling, which underlies multiple divergent traits between japonica and indica.

Relevance of Ferroptosis to Cardiotoxicity Caused by Anthracyclines: Mechanisms to Target Treatments.

Anthracyclines (ANTs) are a class of anticancer drugs widely used in oncology. However, the clinical application of ANTs is limited by their cardiotoxicity. The mechanisms underlying ANTs-induced cardiotoxicity (AIC) are complicated and involve oxidative stress, inflammation, topoisomerase 2ß inhibition, pyroptosis, immunometabolism, autophagy, apoptosis, ferroptosis, etc. Ferroptosis is a new form of regulated cell death (RCD) proposed in 2012, characterized by iron-dependent accumulation of reactive oxygen species (ROS) and lipid peroxidation. An increasing number of studies have found that ferroptosis plays a vital role in the development of AIC. Therefore, we aimed to elaborate on ferroptosis in AIC, especially by doxorubicin (DOX). We first summarize the mechanisms of ferroptosis in terms of oxidation and anti-oxidation systems. Then, we discuss the mechanisms related to ferroptosis caused by DOX, particularly from the perspective of iron metabolism of cardiomyocytes. We also present our research on the prevention and treatment of AIC based on ferroptosis. Finally, we enumerate our views on the development of drugs targeting ferroptosis in this emerging field.

Mitochondrial Damage in Myocardial Ischemia/Reperfusion Injury and Application of Natural Plant Products.

Ischemic heart disease (IHD) is currently one of the leading causes of death among cardiovascular diseases worldwide. In addition, blood reflow and reperfusion paradoxically also lead to further death of cardiomyocytes and increase the infarct size. Multiple evidences indicated that mitochondrial function and structural disorders were the basic driving force of IHD. We summed up the latest evidence of the basic associations and underlying mechanisms of mitochondrial damage in the event of ischemia/reperfusion (I/R) injury. This review then reviewed natural plant products (NPPs) which have been demonstrated to mitochondria-targeted therapeutic effects during I/R injury and the potential pathways involved. We realized that NPPs mainly maintained the integrality of mitochondria membrane and ameliorated dysfunction, such as improving abnormal mitochondrial calcium handling and inhibiting oxidative stress, so as to protect cardiomyocytes during I/R injury. This information will improve our knowledge of mitochondrial biology and I/R-induced injury's pathogenesis and exhibit that NPPs hold promise for translation into potential therapies that target mitochondria.

The Airway Microbiota Signatures of Infection and Rejection in Lung Transplant Recipients.

Infection and rejection are the two most common complications after lung transplantation (LT) and are associated with increased morbidity and mortality. We aimed to examine the association between the airway microbiota and infection and rejection in lung transplant recipients (LTRs). Here, we collected 181 sputum samples (event-free, n = 47; infection, n = 103; rejection, n = 31) from 59 LTRs, and performed 16S rRNA gene sequencing to analyze the airway microbiota. A significantly different airway microbiota was observed among event-free, infection and rejection recipients, including microbial diversity and community composition. Nineteen differential taxa were identified by linear discriminant analysis (LDA) effect size (LEfSe), with 6 bacterial genera, Actinomyces, Rothia, Abiotrophia, Neisseria, Prevotella, and Leptotrichia enriched in LTRs with rejection. Random forest analyses indicated that the combination of the 6 genera and procalcitonin (PCT) and T-lymphocyte levels showed area under the curve (AUC) values of 0.898, 0.919 and 0.895 to differentiate between event-free and infection recipients, event-free and rejection recipients, and infection and rejection recipients, respectively. In conclusion, our study compared the airway microbiota between LTRs with infection and acute rejection. The airway microbiota, especially combined with PCT and T-lymphocyte levels, showed satisfactory predictive efficiency in discriminating among clinically stable recipients and those with infection and acute rejection, suggesting that the airway microbiota can be a potential indicator to differentiate between infection and acute rejection after LT. IMPORTANCE Survival after LT is limited compared with other solid organ transplantations mainly due to infection- and rejection-related complications. Differentiating infection from rejection is one of the most important challenges to face after LT. Recently, the airway microbiota has been reported to be associated with either infection or rejection of LTRs. However, fewer studies have investigated the relationship between airway microbiota together with infection and rejection of LTRs. Here, we conducted an airway microbial study of LTRs and analyzed the airway microbiota together with infection, acute rejection, and clinically stable recipients. We found different airway microbiota between infection and acute rejection and identify several genera associated with each outcome and constructed a model that incorporates airway microbiota and clinical parameters to predict outcome. This study highlighted that the airway microbiota was a potential indicator to differentiate between infection and acute rejection after LT.