Targeting SOX13 inhibits assembly of respiratory chain supercomplexes to overcome ferroptosis resistance in gastric cancer.

Therapeutic resistance represents a bottleneck to treatment in advanced gastric cancer (GC). Ferroptosis is an iron-dependent form of non-apoptotic cell death and is associated with anti-cancer therapeutic efficacy. Further investigations are required to clarify the underlying mechanisms. Ferroptosis-resistant GC cell lines are constructed. Dysregulated mRNAs between ferroptosis-resistant and parental cell lines are identified. The expression of SOX13/SCAF1 is manipulated in GC cell lines where relevant biological and molecular analyses are performed. Molecular docking and computational screening are performed to screen potential inhibitors of SOX13. We show that SOX13 boosts protein remodeling of electron transport chain (ETC) complexes by directly transactivating SCAF1. This leads to increased supercomplexes (SCs) assembly, mitochondrial respiration, mitochondrial energetics and chemo- and immune-resistance. Zanamivir, reverts the ferroptosis-resistant phenotype via directly targeting SOX13 and promoting TRIM25-mediated ubiquitination and degradation of SOX13. Here we show, SOX13/SCAF1 are important in ferroptosis-resistance, and targeting SOX13 with zanamivir has therapeutic potential.

Carbon nanotubes integrated photonic barcodes in Herringbone Microfluidics for Multiplex Biomarker Quantification.

Early monitoring of cardiovascular disease (CVD) is crucial for its treatment and prognosis. Hence, highly specific and sensitive detection method is urgently needed. In this study, we propose a novel herringbone microfluid chip with aptamer functionalized core-shell photonic crystal (PhC) barcode integration for high throughput multiplex CVD detection. Based on the PhC derived from co-assembled carboxylated single-wall carbon nanotubes and silicon dioxide nanoparticles, we obtain core-shell PhC barcodes by hydrogel replicating and partially etching. These core-shell PhC barcodes not only retain the original structural colors coding element, but also fully expose a large number of carboxyl elements in the ore for the probe immobilization. We further combine the functionalized barcodes with herringbone groove microfluidic chip to elucidate its acceptability in testing clinical sample. It is demonstrated that the special design of microfluidic chip can significantly enhance fluid vortex resistance and contact frequency, improving the sample capture efficiency and detection sensitivity. These features indicate that our core-shell PhC barcodes-integrated herringbone microfluidic system possesses great potential for multiplex biomarker detection in clinical application.

A new method based on melatonin-mediated seed germination to quickly remove pesticide residues and improve the nutritional quality of contaminated grains.

In the present study, we attempted to use melatonin combined with germination treatment to remove pesticide residues from contaminated grains. High levels of pesticide residues were detected in soybean seeds after soaking with chlorothalonil (10 mM) and malathion (1 mM) for 2 hours. Treatment with 50 µM melatonin for 5 days completely removed the pesticide residues, while in the control group, only 61-71% of pesticide residues were removed from soybean sprouts. Compared with the control, melatonin treatment for 7 days further increased the content of ascorbic acid (by 48-66%), total phenolics (by 52-68%), isoflavones (by 22-34%), the total antioxidant capacity (by 37-40%), and the accumulated levels of unsaturated fatty acids (C18:1, C18:2, and C18:3) (by 17-30%) in soybean sprouts. Moreover, melatonin treatment further increased the accumulation of ten components of phenols and isoflavones in soybean sprouts relative to those in the control. The ability of melatonin to accelerate the degradation of pesticide residues and promote the accumulation of antioxidant metabolites might be related to its ability to trigger the glutathione detoxification system in soybean sprouts. Melatonin promoted glutathione synthesis (by 49-139%) and elevated the activities of glutathione-S-transferase (by 24-78%) and glutathione reductase (by 38-61%). In summary, we report a new method in which combined treatment by melatonin and germination rapidly degrades pesticide residues in contaminated grains and improves the nutritional quality of food.

Characterizing the Loss and Acquisition of Tn2-like Transposon in Klebsiella pneumoniae: Implications for Carbapemase Gene Dissemination.

Over one year, two KPC-producing and two non-KPC-producing Klebsiella pneumoniae strains were isolated from a patient. Genome and DNA hybridization analyses revealed the first three strains as a clonal lineage, with carbapenem resistance changes due to a Tn2-like transposon on an IncR/IncFII plasmid. The fourth strain, carrying three plasmids, caused a lethal infection and represented a different lineage. All strains belonged to the ST11-SL47-OL101 type. This study highlights the Tn2-like transposon's role in carbapenemase gene spread and the importance of distinguishing between bacterial colonization and infection.

Gut phageome: challenges in research and impact on human microbiota.

The human gut microbiome plays a critical role in maintaining our health. Fluctuations in the diversity and structure of the gut microbiota have been implicated in the pathogenesis of several metabolic and inflammatory conditions. Dietary patterns, medication, smoking, alcohol consumption, and physical activity can all influence the abundance of different types of microbiota in the gut, which in turn can affect the health of individuals. Intestinal phages are an essential component of the gut microbiome, but most studies predominantly focus on the structure and dynamics of gut bacteria while neglecting the role of phages in shaping the gut microbiome. As bacteria-killing viruses, the distribution of bacteriophages in the intestine, their role in influencing the intestinal microbiota, and their mechanisms of action remain elusive. Herein, we present an overview of the current knowledge of gut phages, their lifestyles, identification, and potential impact on the gut microbiota.

How does the development of the digital economy influence carbon productivity? The moderating effect of environmental regulation.

Improving carbon productivity is of great significance to China's "30 · 60" carbon target, while the development of the digital economy is a driving force for green transformation. However, few studies discuss the relationship between the digital economy and carbon productivity. We investigate the influence of digital economic development on carbon productivity using panel data from 30 Chinese provinces from 2011 to 2020. Spatial econometric and moderating effects are considered. The results show that (i) digital economy has a positive direct and negative spatial spillover effect on carbon productivity, and this conclusion is still valid after the robustness test and endogeneity test; (ii) digital infrastructure has a greater impact on carbon productivity than digital industrialization and industrial digitalization; (iii) the mechanism analysis shows that environmental regulation negatively moderates the relationship between the digital economy and carbon productivity; (iv) heterogeneity analysis shows that the effect of the digital economy on carbon productivity is more obvious in the central region compared to the western region, while it is not significant in the eastern region. Overall, this paper not only provides a new analytical perspective for understanding the improvement of carbon productivity in the digital economy but also provides policy inspiration for promoting carbon peak and carbon neutrality goals.

Impact of resistance exercise on patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) has become an increasingly important public health disease with a high incidence rate and mortality. Although several studies have explored the effectiveness of resistance exercise in improving the prognosis of CKD patients, the number of studies is still limited and the results are still controversial. OBJECTIVES: We conducted this meta-analysis of randomized controlled trials (RCT) studies to evaluate the effectiveness of resistance exercise on CKD patients. METHODS: The PubMed, Embase, and Cochrane Library databases were searched from the inception date to October 2023. The meta-analysis was conducted to evaluate 12 main indicators, including glomerular filtration rate (GFR)(ml/(min•1.73m2)), C-reactive protein (CRP) (mg/L), serum creatinine (mg/dL), hemoglobin (g/dL), Glycosylated Hemoglobin, Type A1C (HBA1c) (%), high Density Lipoprotein (HDL) (mg/dL), low Density Lipoprotein (LDL) (mg/dL), 6-min walk(m), body mass index (BMI) (kg/m2), fat-free mass (kg), fat mass (kg), grip strength (kgf). RESULTS: Sixteen RCT studies were included in this meta-analysis from 875 records. GFR exhibited no significant change in CKD patients treated with resistance exercise (WMD 1.82; 95%CI -0.59 to 4.23; P = 0.139). However, 6-min walk (WMD 89.93; 95%CI 50.12 to 129.74; P = 0.000), fat-free mass (WMD 6.53; 95%CI 1.14 to 11.93; P = 0.018) and grip strength (WMD 3.97; 95%CI 1.89 to 6.05; P = 0.000) were significantly improved with resistance exercise. The level of CRP (WMD - 2.46; 95%CI -4.21 to -0.72; P = 0.006) and HBA1c (WMD - 0.46; 95%CI -0.63 to -0.29; P = 0.000) dropped significantly after resistance exercise treatment. CONCLUSIONS: Resistance exercise can improve physical function, metabolic condition, inflammatory response and cardiopulmonary function in CKD patients, specifically reflected in the increase of indicators fat-free mass, grip strength, 6-min walk, as well as the decrease of indicators HBA1c and CRP.

A Comparative Study of Two Radiomics-Based Blood Flow Modes with Thyroid Imaging Reporting and Data System in Predicting Malignancy of Thyroid Nodules and Reducing Unnecessary Fine-Needle Aspiration Rate.

RATIONALE AND OBJECTIVES: We aimed to compare superb microvascular imaging (SMI)-based radiomics methods, and contrast-enhanced ultrasound (CEUS)-based radiomics methods to the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) for classifying thyroid nodules (TNs) and reducing unnecessary fine-needle aspiration biopsy (FNAB) rate. MATERIALS AND METHODS: This retrospective study enrolled a dataset of 472 pathologically confirmed TNs. Radiomics characteristics were extracted from B-mode ultrasound (BMUS), SMI, and CEUS images, respectively. After eliminating redundant features, four radiomics scores (Rad-scores) were constructed. Using multivariable logistic regression analysis, four radiomics prediction models incorporating Rad-score and corresponding US features were constructed and validated in terms of discrimination, calibration, decision curve analysis, and unnecessary FNAB rate. RESULTS: The diagnostic performance of the BMUS + SMI radiomics method was better than ACR TI-RADS (area under the curve [AUC]: 0.875 vs. 0.689 for the training cohort, 0.879 vs. 0.728 for the validation cohort) (P < 0.05), and comparable with BMUS + CEUS radiomics method (AUC: 0.875 vs. 0.878 for the training cohort, 0.879 vs. 0.865 for the validation cohort) (P > 0.05). Decision curve analysis showed that the BMUS+SMI radiomics method could achieve higher net benefits than the BMUS radiomics method and ACR TI-RADS when the threshold probability was between 0.13 and 0.88 in the entire cohort. When applying the BMUS+SMI radiomics method, the unnecessary FNAB rate reduced from 43.4% to 13.9% in the training cohort and from 45.6% to 18.0% in the validation cohorts in comparison to ACR TI-RADS. CONCLUSION: The dual-modal SMI-based radiomics method is convenient and economical and can be an alternative to the dual-modal CEUS-based radiomics method in helping radiologists select the optimal clinical strategy for TN management.

Effects of Simulated Acid Rain on Photosynthesis in Pinus massoniana and Cunninghamia lanceolata in Terms of Prompt Fluorescence, Delayed Fluorescence, and Modulated Reflection at 820 nm.

The effects of simulated acid rain (SAR) on the photosynthetic performance of subtropical coniferous species have not been thoroughly investigated. In this study, we treated two coniferous species, Pinus massoniana (PM) and Cunninghamia lanceolata (CL), with four gradients of SAR and then analyzed their photosynthetic activities through measurements of gas exchange, prompt fluorescence (PF), delayed fluorescence (DF), and modulated reflection at 820 nm (MR820). Gas exchange analysis indicated that the decrease in the net photosynthetic rate (Pn) in PM and CL was unrelated to stomatal factors. For the PF transients, SAR induced positive K-band and L-band, a significant reduction in photosynthetic performance index (PIABS), the quantum yield of electron transfer per unit cross-section (ETO/CSm), and maximal photochemical efficiency of photosystem II (Fv/Fm). Analysis of the MR820 kinetics showed that the re-reduction kinetics of PSI reaction center (P700+) and plastocyanin (PC+) became slower and occurred at later times under SAR treatment. For the DF signals, a decrease in the amplitude of the DF induction curve reduced the maximum value of DF (I1). These results suggested that SAR obstructed photosystem II (PSII) donor-side and acceptor-side electron transfer capacity, impaired the connectivity between PSII and PSI, and destroyed the oxygen-evolving complex (OEC). However, PM was better able to withstand SAR stress than CL, likely because of the activation of a protective mechanism.

Blockade of C5aR1 resets M1 via gut microbiota-mediated PFKM stabilization in a TLR5-dependent manner.

Targeting C5aR1 modulates the function of infiltrated immune cells including tumor-associated macrophages (TAMs). The gut microbiome plays a pivotal role in colorectal cancer (CRC) tumorigenesis and development through TAM education. However, whether and how the gut flora is involved in C5aR1 inhibition-mediated TAMs remains unclear. Therefore, in this study, genetic deletion of C5ar1 or pharmacological inhibition of C5aR1 with anti-C5aR1 Ab or PMX-53 in the presence or absence of deletion Abs were utilized to verify if and how C5aR1 inhibition regulated TAMs polarization via affecting gut microbiota composition. We found that the therapeutic effects of C5aR1 inhibition on CRC benefited from programming of TAMs toward M1 polarization via driving AKT2-mediated 6-phosphofructokinase muscle type (PFKM) stabilization in a TLR5-dependent manner. Of note, in the further study, we found that C5aR1 inhibition elevated the concentration of serum IL-22 and the mRNA levels of its downstream target genes encoded antimicrobial peptides (AMPs), leading to gut microbiota modulation and flagellin releasement, which contributed to M1 polarization. Our data revealed that high levels of C5aR1 in TAMs predicted poor prognosis. In summary, our study suggested that C5aR1 inhibition reduced CRC growth via resetting M1 by AKT2 activation-mediated PFKM stabilization in a TLR5-dependent manner, which relied on IL-22-regulated gut flora.

Diphylleia Grayi-Inspired Intelligent Temperature-Responsive Transparent Nanofiber Membranes.

Nanofiber membranes (NFMs) have become attractive candidates for next-generation flexible transparent materials due to their exceptional flexibility and breathability. However, improving the transmittance of NFMs is a great challenge due to the enormous reflection and incredibly poor transmission generated by the nanofiber-air interface. In this research, we report a general strategy for the preparation of flexible temperature-responsive transparent (TRT) membranes, which achieves a rapid transformation of NFMs from opaque to highly transparent under a narrow temperature window. In this process, the phase change material eicosane is coated on the surface of the polyurethane nanofibers by electrospray technology. When the temperature rises to 37 °C, eicosane rapidly completes the phase transition and establishes the light transmission path between the nanofibers, preventing light loss from reflection at the nanofiber-air interface. The resulting TRT membrane exhibits high transmittance (> 90%), and fast response (5 s). This study achieves the first TRT transition of NFMs, offering a general strategy for building highly transparent nanofiber materials, shaping the future of next-generation intelligent temperature monitoring, anti-counterfeiting measures, and other high-performance devices.

Multitargeted Immunomodulatory Therapy for Viral Myocarditis by Engineered Extracellular Vesicles.

Immune regulation therapies are considered promising for treating classically activated macrophage (M1)-driven viral myocarditis (VM). Alternatively, activated macrophage (M2)-derived extracellular vesicles (M2 EVs) have great immunomodulatory potential owing to their ability to reprogram macrophages, but their therapeutic efficacy is hampered by insufficient targeting capacity in vivo. Therefore, we developed cardiac-targeting peptide (CTP) and platelet membrane (PM)-engineered M2 EVs enriched with viral macrophage inflammatory protein-II (vMIP-II), termed CTP/PM-M2 EVsvMIP-II-Lamp2b, to improve the delivery of EVs "cargo" to the heart tissues. In a mouse model of VM, the intravenously injected CTP/PM-M2 EVsvMIP-II-Lamp2b could be carried into the myocardium via CTP, PM, and vMIP-II. In the inflammatory microenvironment, macrophages differentiated from circulating monocytes and macrophages residing in the heart showed enhanced endocytosis rates for CTP/PM-M2 EVsvMIP-II-Lamp2b. Subsequently, CTP/PM-M2 EVsvMIP-II-Lamp2b successfully released functional M2 EVsvMIP-II-Lamp2b into the cytosol, which facilitated the reprogramming of inflammatory M1 macrophages to reparative M2 macrophages. vMIP-II not only helps to increase the targeting ability of M2 EVs but also collaborates with M2 EVs to regulate M1 macrophages in the inflammatory microenvironment and downregulate the levels of multiple chemokine receptors. Finally, the cardiac immune microenvironment was protectively regulated to achieve cardiac repair. Taken together, our findings suggest that CTP-and-PM-engineered M2 EVsvMIP-II-Lamp2b represent an effective means for treating VM and show promise for clinical applications.

Transition to healthier lifestyle associated with reduced risk of incident dementia and decreased hippocampal atrophy.

BACKGROUND: Research has estimated the associations of lifestyle at one-time point with the risk of dementia and hippocampal volume, but the impact of lifestyle transition on dementia and hippocampal volume remains unclear. This study aims to examine the associations of lifestyle transition with the risk of dementia and hippocampal volume. METHODS: Based on data from the UK Biobank, a weighted lifestyle score was constructed by incorporating six lifestyle factors. Within each baseline lifestyle group (i.e., healthy, intermediate, and unhealthy), lifestyle transition was classified into decline, maintenance, and improvement. Cox proportional hazard regression was used to estimate the association of lifestyle transition and incident dementia (N = 16,305). A multiple linear regression model was used to estimate the association between lifestyle transition and hippocampal volume (N = 5849). RESULTS: During a median follow-up period of 8.6 years, 120 (0.7 %) dementia events were documented. Among participants with healthy baseline lifestyles, the improvement group had a lower risk of incident dementia (HR: 0.18, 95 % CI: 0.04-0.81) and a larger hippocampal volume (ß = 111.69, P = 0.026) than the decline group. Similar results were observed among participants with intermediate baseline lifestyles regarding dementia risk but not hippocampal volume. No benefits were observed in the improvement group among those with unhealthy baseline lifestyles. LIMITATIONS: A lower incidence of dementia than other cohort study and this may have resulted in an underestimation of the risk of dementia. CONCLUSIONS: Earlier transitions to healthier lifestyle were associated with reduced risk of incident dementia and decreased hippocampal atrophy.

Temperature dependence of carbon metabolism in the leaves in sun and shade in a subtropical forest.

Rising temperatures pose a threat to the stability of climate regulation by carbon metabolism in subtropical forests. Although the effects of temperature on leaf carbon metabolism traits in sun-exposed leaves are well understood, there is limited knowledge about its impacts on shade leaves and the implications for ecosystem-climate feedbacks. In this study, we measured temperature response curves of photosynthesis and respiration for 62 woody species in summer (including both evergreen and deciduous species) and 20 evergreen species in winter. The aim was to uncover the temperature dependence of carbon metabolism in both sun and shade leaves in subtropical forests. Our findings reveal that shade had no significant effects on the mean optimum photosynthetic temperatures (TOpt) or temperature range (T90). However, there were decreases observed in mean stomatal conductance, mean area-based photosynthetic rates at TOpt and 25 °C, as well as mean area-based dark respiration rates at 25 °C in both evergreen and deciduous species. Moreover, the respiration-temperature sensitivity (Q10) of sun leaves was higher than that of shade leaves in winter, with the reverse being true in summer. Leaf economics spectrum traits, such as leaf mass per area, and leaf concentration of nitrogen and phosphorus across species, proved to be good predictors of TOpt, T90, mass-based photosynthetic rate at TOpt, and mass-based photosynthetic and respiration rate at 25 °C. However, Q10 was poorly predicted by these leaf economics spectrum traits except for shade leaves in winter. Our results suggest that model estimates of carbon metabolism in multilayered subtropical forest canopies do not necessitate independent parameterization of T90 and TOpt temperature responses in sun and shade leaves. Nevertheless, a deeper understanding and quantification of canopy variations in Q10 responses to temperature are necessary to confirm the generality of temperature-carbon metabolism trait responses and enhance ecosystem model estimates of carbon dynamics under future climate warming.

Respiration in light of evergreen and deciduous woody species and its links to the leaf economic spectrum.

Leaf respiration in the light (Rlight) is crucial for understanding the net CO2 exchange of individual plants and entire ecosystems. However, Rlight is poorly quantified and rarely discussed in the context of the leaf economic spectrum (LES), especially among woody species differing in plant functional types (PFTs) (e.g., evergreen vs. deciduous species). To address this gap in our knowledge, Rlight, respiration in the dark (Rdark), light-saturated photosynthetic rates (Asat), leaf dry mass per unit area (LMA), leaf nitrogen (N) and phosphorus (P) concentrations, and maximum carboxylation (Vcmax) and electron transport rates (Jmax) of 54 representative subtropical woody evergreen and deciduous species were measured. With the exception of LMA, the parameters quantified in this study were significantly higher in deciduous species than in evergreen species. The degree of light inhibition did not significantly differ between evergreen (52%) and deciduous (50%) species. Rlight was significantly correlated with LES traits such as Asat, Rdark, LMA, N and P. The Rlight vs. Rdark and N relationships shared common slopes between evergreen and deciduous species, but significantly differed in their y-intercepts, in which the rates of Rlight were slower or faster for any given Rdark or N in deciduous species, respectively. A model for Rlight based on three traits (i.e., Rdark, LMA and P) had an explanatory power of 84.9%. These results show that there is a link between Rlight and the LES, and highlight that PFTs is an important factor in affecting Rlight and the relationships of Rlight with Rdark and N. Thus, this study provides information that can improve the next generation of terrestrial biosphere models (TBMs).

Accelerated aging mediates the associations of unhealthy lifestyles with cardiovascular disease, cancer, and mortality.

BACKGROUND: With two well-validated aging measures capturing mortality and morbidity risk, this study examined whether and to what extent aging mediates the associations of unhealthy lifestyles with adverse health outcomes. METHODS: Data were from 405,944 adults (40-69 years) from UK Biobank (UKB) and 9972 adults (20-84 years) from the US National Health and Nutrition Examination Survey (NHANES). An unhealthy lifestyles score (range: 0-5) was constructed based on five factors (smoking, drinking, physical inactivity, unhealthy body mass index, and unhealthy diet). Two aging measures, Phenotypic Age Acceleration (PhenoAgeAccel) and Biological Age Acceleration (BioAgeAccel) were calculated using nine and seven blood biomarkers, respectively, with a higher value indicating the acceleration of aging. The outcomes included incident cardiovascular disease (CVD), incident cancer, and all-cause mortality in UKB; CVD mortality, cancer mortality, and all-cause mortality in NHANES. A general linear regression model, Cox proportional hazards model, and formal mediation analysis were performed. RESULTS: The unhealthy lifestyles score was positively associated with PhenoAgeAccel (UKB: ß = 0.741; NHANES: ß = 0.874, all p < 0.001). We further confirmed the respective associations of PhenoAgeAccel and unhealthy lifestyles with the outcomes in UKB and NHANES. The mediation proportion of PhenoAgeAccel in associations of unhealthy lifestyles with incident CVD, incident cancer, and all-cause mortality were 20.0%, 17.8%, and 26.6% (all p < 0.001) in UKB, respectively. Similar results were found in NHANES. The findings were robust when using another aging measure-BioAgeAccel. CONCLUSIONS: Accelerated aging partially mediated the associations of lifestyles with CVD, cancer, and mortality in UK and US populations. The findings reveal a novel pathway and the potential of geroprotective programs in mitigating health inequality in late life beyond lifestyle interventions.

Transcriptome and photosynthetic analyses provide new insight into the molecular mechanisms underlying heat stress tolerance in Rhododendron × pulchrum Sweet.

Rhododendron species provide excellent ornamental use worldwide, yet heat stress (HS) is one of the major threats to their cultivation. However, the intricate mechanisms underlying the photochemical and transcriptional regulations associated with the heat stress response in Rhododendron remain relatively unexplored. In this study, the analyses of morphological characteristics and chlorophyll fluorescence (ChlF) kinetics showed that HS (40 °C/35 °C) had a notable impact on both the donor's and acceptor's sides of photosystem II (PSII), resulting in reduced PSII activity and electron transfer capacity. The gradual recovery of plants observed following a 5-day period of culture under normal conditions indicates the reversible nature of the HS impact on Rhododendron × pulchrum. Analysis of transcriptome data unveiled noteworthy trends: four genes associated with photosynthesis-antenna protein synthesis (LHCb1, LHCb2 and LHCb3) and the antioxidant system (glutamate-cysteine ligase) experienced significant down-regulation in the leaves of R. × pulchrum during HS. Conversely, aseorbate peroxidase and glutathione S-transferase TAU 8 demonstrated an up-regulated pattern. Furthermore, six down-regulated genes (phos-phoenolpyruvate carboxylase 4, sedoheptulose-bisphosphatase, ribose-5-phosphate isomerase 2, high cyclic electron flow 1, beta glucosidase 32 and starch synthase 2) and two up-regulated genes (beta glucosidase 2 and UDP-glucose pyrophosphorylase 2) implicated in photosynthetic carbon fixation and starch/sucrose metabolism were identified during the recovery process. To augment these insights, a weighted gene co-expression network analysis yielded a co-expression network, pinpointing the hub genes correlated with ChlF dynamics' variation trends. The cumulative results showed that HS inhibited the synthesis of photosynthesis-antenna proteins in R. × pulchrum leaves. This disruption subsequently led to diminished photochemical activities in both PSII and PSI, albeit with PSI exhibiting heightened thermostability. Depending on the regulation of the reactive oxygen species scavenging system and heat dissipation, photoprotection sustained the recoverability of R. × pulchrum to HS.

Association of Childhood Adversity With Frailty and the Mediating Role of Unhealthy Lifestyle: A Lifespan Analysis.

OBJECTIVES: Childhood adversity and lifestyle have been associated with frailty in later life, but not much is known about factors that may explain these associations. Therefore, this study aims to investigate the association of childhood adversity with frailty, and the mediating role of unhealthy lifestyle in the association. METHODS: This lifespan analysis included 152,914 adults aged 40-69 years old from the UK Biobank. We measured childhood adversity with five items: physical neglect, emotional neglect, sexual abuse, physical abuse, and emotional abuse through online mental health survey. Frailty was measured by the frailty index; an unhealthy lifestyle score (range: 0-5) was calculated based on unhealthy body mass index, smoking, alcohol consumption, physical inactivity, and unhealthy diet at the baseline survey. Multiple logistic regression and mediation analysis were performed. RESULTS: A total of 10,078 participants (6.6%) were defined as having frailty. Participants with any childhood adversity had higher odds of frailty. For example, in the fully adjusted model, with a one-point increase in cumulative score of childhood adversity, the odds of frailty increased by 38% (odds ratio: 1.38; 95% Confidence Interval: 1.36, 1.40). Unhealthy lifestyle partially mediated the associations of childhood adversity with frailty (mediation proportion: 4.4%-7.0%). The mediation proportions were largest for physical (8.2%) and sexual (8.1%) abuse. CONCLUSIONS: Childhood adversity was positively associated with frailty, and unhealthy lifestyle partially mediated the association. This newly identified pathway highlights the potential of lifestyle intervention strategies among those who experienced childhood adversity (in particular, physical, and sexual abuse) to promote healthy aging.

M2 macrophage exosome-derived lncRNA AK083884 protects mice from CVB3-induced viral myocarditis through regulating PKM2/HIF-1α axis mediated metabolic reprogramming of macrophages.

Viral myocarditis (VM) is a clinically common inflammatory disease. Accumulating literature has indicated that M2 macrophages protect mice from Coxsackievirus B3 (CVB3)-induced VM. However, mechanisms that underlie M2 macrophages alleviating myocardial inflammation remain largely undefined. We found that M2 macrophage-derived exosomes (M2-Exo) can effectively attenuate VM. The long non-coding RNA (lncRNA) AK083884 in M2-Exo was found to be involved in the regulation of macrophage polarization by exosome lncRNA sequencing combined with in vitro functional assays. M2-Exo-derived AK083884 promotes macrophage M2 polarization and protects mice from CVB3-induced VM. Furthermore, we identified pyruvate kinase M2 (PKM2) as a protein target binding to AK083884 and found that PKM2 knockdown could promote macrophages to polarize to M2 phenotype. Intriguingly, functional assay revealed that downregulation of AK083884 promotes metabolic reprogramming in macrophages. In addition, co-immunoprecipitation was performed to reveal AK083884 could interact with PKM2 and inhibition of AK083884 can facilitate the binding of PKM2 and HIF-1α. Collectively, our findings uncovered an important role of M2-Exo-derived AK083884 in the regulation of macrophage polarization through metabolic reprogramming, identified a new participant in the development of VM and provided a potential clinically important therapeutic target.

First Report of Calonectria ilicicola causing Leaf spot on Camellia sinensis in Yunnan province, China.

Tea (Camellia sinensis (L.) Kuntze) is among the most significant industrial crops due to its distinctive fragrance and flavor generated (Bag et al. 2022). From October to December in 2021, a leaf spot disease affected the quality and yield of tea (C. sinensis var. assamica cv. Yunkang 10), in Pu'er (100.57°E, 22.45°N), Yunnan province, China. Based on the survey, the incidence was approximately 15% in a plantation of 4500 m2 (2050 tea trees approximately). The symptoms on leaves were regular circular, dark brown lesions with black conidiomata in gray centers. Twenty symptomatic leaves were collected from 10 trees. After rinsing and surface sterilization (75% ethanol for 30 s and 3% NaClO for 90 s, rinsed 3 times with sterile distilled water), diseased tissues (5 × 5 mm) were cut at the junction of infected and healthy site and placed on potato dextrose agar (PDA) (3 pieces per plate) and incubated in the dark at 28℃ for 5 days (Mao et al. 2023). Three single-spore isolates 6a-H-1, 6a-H-2 and 6a-H-3 were obtained, which showed identical in morphology and molecular analysis. Therefore, the targeted isolate 6a-H-2 was used for further study. Fungal colonies were white, then gradually turning into goose yellow (Fig.2. A-C). Chlamydospores were dark brown and oval (Fig.2. G). Asci produced after 30 days approximately, were orange-red, nearly spherical, rough-surface, and measured as 470 µm ± 11.68 µm (n = 50) (Fig.2. H). Ascospores were released from the asci orifice (Fig.2. I) which were hyaline, fusoid with rounded ends, straight to slightly curved, two septate, slightly constricted at the septum, and ranged from 48.77 ± 2.76 µm × 6.22 ± 0.41 µm (n = 50) (Fig.2. D-F). Macroconidia were cylindrical (Fig.2. J), rounded at both ends, straight, with an average length of 63.5 ± 0.31 µm × 2.62 ± 0.03 µm without septa (n=50) (Fig.2. M-O). Stipe extension terminated in sphaero-pedunculate vesicles (Fig.2. K-L). The morphological features were consistent with the descriptions of Calonectria ilicicola (Pei et al. 2015; Polizzi et al. 2012). The pathogen was confirmed to be C. ilicicola by amplification and sequencing of the histone (HIS3), translation elongation factor 1-alpha (TEF1) and calmodulin (CAL) genes using primers H3-3F/H3-3R, EF1-728F/EF1-986R and CAL-228F/CAL-2Rd, respectively (Crous et al. 2004). The sequences of PCR products were deposited in GenBank with accession numbers OR188222 (HIS3), OR188223 (TEF1) and OR188221 (CAL). BLAST searches of the obtained sequences revealed 99.22% (510/514 nucleotides), 98.37% (241/245 nucleotides) and 99.58% (472/474 nucleotides) homology with those of C. ilicicola (CBS 190.50) in GenBank (AY725676, AY725726 and AY725764), respectively. Phylogenetic analysis (MEGA 7.0) using the Maximum Likelihood method placed the isolate 6a-H-2 in a well-supported cluster with C. ilicicola. The pathogenicity of 6a-H-2 was tested through a pot assay. Five healthy plants had their leaves scratched with a sterilized needle, then inoculated by spraying 20 mL of spore suspension (105 spores mL-1) of 6a-H-2. Five additional tea plants sprayed with sterile distilled water served as controls. All plants were placed in a growth chamber at 28℃, with 70% relative humidity. The symptoms developed on all inoculated leaves but not on the control leaves. The lesions were first visible 72 h after inoculation, and typical lesions similar to those observed on field plants appeared after 10 days. The same fungus was reisolated and identified based on the morphology and molecular analyses (HIS3, TEF1 and CAL) from the infected leaves but not from the non-inoculated leaves. To our knowledge, this is the first report of leaf spot on tea caused by C. ilicicola in China. This study provides valuable information for the identification and control of the leaf spot on tea.