Magnaporthe oryzae Effector AvrPik-D Targets Rice Rubisco Small Subunit OsRBCS4 to Suppress Immunity.

Rice blast, caused by the fungal pathogen Magnaporthe oryzae (M. oryzae), is a highly destructive disease that significantly impacts rice yield and quality. During the infection, M. oryzae secretes effector proteins to subvert the host immune response. However, the interaction between the effector protein AvrPik-D and its target proteins in rice, and the mechanism by which AvrPik-D exacerbates disease severity to facilitate infection, remains poorly understood. In this study, we found that the M. oryzae effector AvrPik-D interacts with the Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase) small subunit OsRBCS4. The overexpression of the OsRBCS4 gene in transgenic rice not only enhances resistance to M. oryzae but also induces more reactive oxygen species following chitin treatment. OsRBCS4 localizes to chloroplasts and co-localizes with AvrPik-D within these organelles. AvrPik-D suppresses the transcriptional expression of OsRBCS4 and inhibits Rubisco activity in rice. In conclusion, our results demonstrate that the M. oryzae effector AvrPik-D targets the Rubisco small subunit OsRBCS4 and inhibits its carboxylase and oxygenase activity, thereby suppressing rice innate immunity to facilitate infection. This provides a novel mechanism for the M. oryzae effector to subvert the host immunity to promote infection.

One-Dimensional Covalent Organic Framework with Improved Charge Transfer for Enhanced Electrochemiluminescence.

We present a dimensional regulating charge transfer strategy to achieve an enhanced electrochemiluminescence (ECL) by constructing a one-dimensional pyrene-based covalent organic framework (1D-COF). The dual-chain-like edge architecture in 1D-COF facilitates the stabilization of aromatic backbones, the enhancement of electronic conjugations, and the decrease of energy loss. The 1D-COF generates enhanced anodic (92.5-fold) and cathodic (3.2-fold) signals with tripropylamine (TPrA) and K2S2O8 as the anodic and cathodic coreactants, respectively, compared with 2D-COF. The anodic and cathodic ECL efficiencies of 1D-COF are 2.08- and 3.08-fold higher than those of 2D-COF, respectively. According to density functional theory (DFT), the rotational barrier energy (ΔE) of 1D-COF enhances sharply with the increase of dihedral angle, suggesting that the architecture in 1D-COF restrains the intramolecular spin of aromatic chains, which facilitates the decrease of nonradiative transitions and the enhancement of ECL. Furthermore, 1D-COF can be used to construct an ECL biosensor for sensitive detection of dopamine.

Response of photosynthetic characteristics and antioxidant system in the leaves of safflower to NaCl and NaHCO3.

KEY MESSAGE: Compared with NaCl, NaHCO3 caused more serious oxidative damage and photosynthesis inhibition in safflower by down-regulating the expression of related genes. Salt-alkali stress is one of the important factors that limit plant growth. NaCl and sodium bicarbonate (NaHCO3) are neutral and alkaline salts, respectively. This study investigated the physiological characteristics and molecular responses of safflower (Carthamus tinctorius L.) leaves treated with 200 mmol L-1 of NaCl or NaHCO3. The plants treated with NaCl treatment were less effective at inhibiting the growth of safflower, but increased the content of malondialdehyde (MDA) in leaves. Meanwhile, safflower alleviated stress damage by increasing proline (Pro), soluble protein (SP), and soluble sugar (SS). Both fresh weight and dry weight of safflower was severely decreased when it was subjected to NaHCO3 stress, and there was a significant increase in the permeability of cell membranes and the contents of osmotic regulatory substances. An enrichment analysis of the differentially expressed genes (DEGs) using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes identified significant enrichment of photosynthesis and pathways related to oxidative stress. Furthermore, a weighted gene co-expression network analysis (WGCNA) showed that the darkgreen module had the highest correlation with photosynthesis and oxidative stress traits. Large numbers of transcription factors, primarily from the MYB, GRAS, WRKY, and C2H2 families, were predicted from the genes within the darkgreen module. An analysis of physiological indicators and DEGs, it was found that under saline-alkali stress, genes related to chlorophyll synthesis enzymes were downregulated, while those related to degradation were upregulated, resulting in inhibited chlorophyll biosynthesis and decreased chlorophyll content. Additionally, NaCl and NaHCO3 stress downregulated the expression of genes related to the Calvin cycle, photosynthetic antenna proteins, and the activity of photosynthetic reaction centers to varying degrees, hindering the photosynthetic electron transfer process, suppressing photosynthesis, with NaHCO3 stress causing more pronounced adverse effects. In terms of oxidative stress, the level of reactive oxygen species (ROS) did not change significantly under the NaCl treatment, but the contents of hydrogen peroxide and the rate of production of superoxide anions increased significantly under NaHCO3 stress. In addition, treatment with NaCl upregulated the levels of expression of the key genes for superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), the ascorbate-glutathione cycle, and the thioredoxin-peroxiredoxin pathway, and increased the activity of these enzymes, thus, reducing oxidative damage. Similarly, NaHCO3 stress increased the activities of SOD, CAT, and POD and the content of ascorbic acid and initiated the glutathione-S-transferase pathway to remove excess ROS but suppressed the regeneration of glutathione and the activity of peroxiredoxin. Overall, both neutral and alkaline salts inhibited the photosynthetic process of safflower, although alkaline salt caused a higher level of stress than neutral salt. Safflower alleviated the oxidative damage induced by stress by regulating its antioxidant system.

Evidence and causes of recent decreases in nitrogen deposition in temperate forests in Northeast China.

High reactive nitrogen (N) emissions due to anthropogenic activities in China have led to an increase in N deposition and ecosystem degradation. The Chinese government has strictly regulated reactive N emissions since 2010, however, determining whether N deposition has reduced requires long-term monitoring. Here, we report the patterns of N deposition at a rural forest site (Qingyuan) in northeastern China over the last decade. We collected 456 daily precipitation samples from 2014 to 2022 and analysed the temporal dynamics of N deposition. NH4+-N, NO3--N, and total inorganic N (TIN) deposition ranged from 10.5 ± 3.5 (mean ± SD), 6.1 ± 1.6, and 16.6 ± 4.7 kg N ha-1 year-1, respectively. Over the measurement period, TIN deposition at Qingyuan decreased by 55 %, whereas that in comparable sites in East Asia declined by 14-34 %. We used a random forest model to determine factors influencing the deposition of NH4+-N, NO3--N, and TIN during the study period. NH4+-N deposition decreased by 60 % because of decreased agricultural NH3 emissions. Furthermore, NO3--N deposition decreased by 42 %, due to reduced NOx emissions from agricultural soil and fossil fuel combustion. The steep decline in N deposition in northeastern China was attributed to reduced coal consumption, improved emission controls on automobiles, and shifts in agricultural practices. Long-term monitoring is needed to assess regional air quality and the impact of N emission control regulations.

Longitudinal Changes in Refractive Development in Highly Hyperopic Children: A 2.6-11.2 Year Follow-up of Preschoolers Diagnosed with High Hyperopia.

PURPOSE: This study aims to elucidate the longitudinal refractive and ocular biometric alterations in preschool children with high hyperopia who underwent early interventions. METHODS: We conducted a retrospective analysis of preschool children diagnosed with high hyperopia at Tianjin Medical University Eye Hospital between 2011 and 2023. Inclusion criteria required an initial examination with cycloplegic refraction, bilateral spherical equivalent power (SE) ≥ +5.00D with a difference <1.00D, a minimum two-year follow-up, and at least three ocular biometric measurements. The annual axial growth rate evaluated emmetropization in highly hyperopic children. We applied Restricted Cubic Spline (RCS) models to explore potential nonlinear relationships between age and spherical equivalent, axial length, corneal curvature, and axial length-to-corneal curvature ratio. Additionally, Mixed-effects models were employed to investigate factors associated with changes in refractive error and axial length. RESULTS: The study enrolled 60 eligible subjects, with a median initial diagnosis age of 3.5 years (IQR, 2.8-4.9 years) and a median last visit age of 9.3 years (IQR, 8.1-10.8 years). The average follow-up duration was 5.7 years. RCS analysis revealed notable nonlinear changes in spherical equivalent power, axial length, and axial length-to-corneal curvature ratio, although corneal curvature displayed no statistically significant nonlinear trend. Factors affecting SE changes included the presence of strabismus, the use of cycloplegia, baseline SE, and age. Conversely, changes in axial length solely correlated with baseline axial length and age. CONCLUSION: Highly hyperopic preschool children undergoing early intervention display a marked emmetropization tendency, though most still remain moderately to highly hyperopic, with the progression of refractive changes showing non-uniform patterns with respect to age.

Computer-aided design to enhance the stability of aldo-keto reductase KdAKR.

The aldo-keto reductase (AKR) KdAKR from Kluyvermyces dobzhanskii can reduce t-butyl 6-chloro-(5S)-hydroxy-3-oxohexanoate ((5S)-CHOH) to t-butyl 6-chloro-(3R,5S)-dihydroxyhexanoate ((3R,5S)-CDHH), which is the key chiral intermediate of rosuvastatin. Herein, a computer-aided design that combined the use of PROSS platform and consensus design was employed to improve the stability of a previously constructed mutant KdAKRM6 . Experimental verification revealed that S196C, T232A, V264I and V45L produced improved thermostability and activity. The "best" mutant KdAKRM10 (KdAKRM6 -S196C/T232A/V264I/V45L) was constructed by combining the four beneficial mutations, which displayed enhanced thermostability. Its T50 15 and Tm values were increased by 10.2 and 10.0°C, respectively, and half-life (t1/2 ) at 40°C was increased by 17.6 h. Additionally, KdAKRM10 demonstrated improved resistance to organic solvents compared to that of KdAKRM6 . Structural analysis revealed that the increased number of hydrogen bonds and stabilized hydrophobic core contributed to the rigidity of KdAKRM10 , thus improving its stability. The results validated the feasibility of the computer-aided design strategy in improving the stability of AKRs.

Nitrogen isotopic characteristics of aerosol ammonium in a Chinese megacity indicate the reduction from vehicle emissions during the lockdown period.

The role of agricultural versus vehicle emissions in urban atmospheric ammonia (NH3) remains unclear. The lockdown due to the outbreak of COVID-19 provided an opportunity to assess the role of source emissions on urban NH3. Concentrations and δ15N of aerosol ammonium (NH4+) were measured before (autumn in 2017) and during the lockdown (summer, autumn, and winter in 2020), and source contributions were quantified using SIAR. Despite the insignificant decrease in NH4+ concentrations, significantly lower δ15N-NH4+ was found in 2020 (0.6 ± 1.0‰ in PM2.5 and 1.4 ± 2.1‰ in PM10) than in 2017 (15.2 ± 6.7‰ in PM2.5), which indicates the NH3 from vehicle emissions has decreased by∼50% during the lockdown while other source emissions are less affected. Moreover, a reversed seasonal pattern of δ15N-NH4+ during the lockdown in Changsha has been revealed compared to previous urban studies, which can be explained by the dominant effect of non-fossil fuel emissions due to the reductions of vehicle emissions during the lockdown period. Our results highlight the effects of lockdown on aerosol δ15N-NH4+ and the importance of vehicle emissions to urban atmospheric NH3, providing conclusive evidence that reducing vehicle NH3 emissions could be an effective strategy to reduce PM2.5 in Chinese megacities.

Magnaporthe oryzae effector AvrPik-D targets a transcription factor WG7 to suppress rice immunity.

Rice blast, caused by the fungal pathogen Magnaporthe oryzae, is one of the most devastating diseases for rice crops, significantly affecting crop yield and quality. During the infection process, M. oryzae secretes effector proteins that help in hijacking the host's immune responses to establish infection. However, little is known about the interaction between the effector protein AvrPik-D and the host protein Pikh, and how AvrPik-D increases disease severity to promote infection. In this study, we show that the M. oryzae effector AvrPik-D interacts with the zinc finger-type transcription factor WG7 in the nucleus and promotes its transcriptional activity. Genetic removal (knockout) of the gene WG7 in transgenic rice enhances resistance to M. oryzae and also results in an increased burst of reactive oxygen species after treatments with chitin. In addition, the hormone level of SA and JA, is increased and decreased respectively in WG7 KO plants, indicating that WG7 may negatively mediate resistance through salicylic acid pathway. Conversely, WG7 overexpression lines reduce resistance to M. oryzae. However, WG7 is not required for the Pikh-mediated resistance against rice blast. In conclusion, our results revealed that the M. oryzae effector AvrPik-D targets and promotes transcriptional activity of WG7 to suppress rice innate immunity to facilitate infection.

Identification and Biological Characteristics of Mortierella alpina Associated with Chinese Flowering Cherry (Cerasus serrulata) Leaf Blight in China.

The Chinese flowering cherry (Cerasus serrulata), an ornamental tree with established medicinal values, is observed to suffer from leaf blight within Xi'an's greenbelts. This disease threatens both the plant's growth and its ornamental appeal. In this study, 26 isolates were obtained from plants with typical leaf blight, and only 3 isolates (XA-10, XA-15, and XA-18) were found to be pathogenic, causing similar symptoms on the leaves of the host plant. Based on sequence alignment, the ITS and LSU sequences of the three selected isolates were consistent, respectively. Following morphological and molecular analyses, the three selected isolates were further identified as Mortierella alpina. The three selected isolates exhibited similar morphological characteristics, including wavy colonies with dense, milky-white aerial mycelia on PDA medium. Therefore, isolate XA-10 was used as a representative strain for subsequent experiments. The representative strain XA-10 was found to exhibit optimal growth at a temperature of 30 °C and a pH of 7.0. Host range infection tests further revealed that the representative strain XA-10 could also inflict comparable disease symptoms on both the leaves and fruits of three different Rosaceae species (Prunus persica, Pyrus bretschneideri, and Prunus salicina). This study reveals, for the first time, the causative agent of leaf blight disease affecting the Chinese flowering cherry. This provides a deeper understanding of the biology and etiology of M. alpina. This study lays a solid foundation for the sustainable control and management of leaf blight disease in the Chinese flowering cherry.

Dominant contribution of combustion-related ammonium during haze pollution in Beijing.

Aerosol ammonium (NH4+), mainly produced from the reactions of ammonia (NH3) with acids in the atmosphere, has significant impacts on air pollution, radiative forcing, and human health. Understanding the source and formation mechanism of NH4+ can provide scientific insights into air quality improvements. However, the sources of NH3 in urban areas are not well understood, and few studies focus on NH3/NH4+ at different heights within the atmospheric boundary layer, which hinders a comprehensive understanding of aerosol NH4+. In this study, we perform both field observation and modeling studies (the Community Multiscale Air Quality, CMAQ) to investigate regional NH3 emission sources and vertically resolved NH4+ formation mechanisms during the winter in Beijing. Both stable nitrogen isotope analyses and CMAQ model suggest that combustion-related NH3 emissions, including fossil fuel sources, NH3 slip, and biomass burning, are important sources of aerosol NH4+ with more than 60% contribution occurring on heavily polluted days. In contrast, volatilization-related NH3 sources (livestock breeding, N-fertilizer application, and human waste) are dominant on clean days. Combustion-related NH3 is mostly local from Beijing, and biomass burning is likely an important NH3 source (∼15%-20%) that was previously overlooked. More effective control strategies such as the two-product (e.g., reducing both SO2 and NH3) control policy should be considered to improve air quality.

Large Seasonal Variation in Nitrogen Isotopic Abundances of Ammonia Volatilized from a Cropland Ecosystem and Implications for Regional NH3 Source Partitioning.

Ammonia (NH3) volatilization from agricultural lands is a main source of atmospheric reduced nitrogen species (NHx). Accurately quantifying its contribution to regional atmospheric NHx deposition is critical for controlling regional air nitrogen pollution. The stable nitrogen isotope composition (expressed by δ15N) is a promising indicator to trace atmospheric NHx sources, presupposing a reliable nitrogen isotopic signature of NH3 emission sources. To obtain more specific seasonal δ15N values of soil NH3 volatilization for reliable regional seasonal NH3 source partitioning, we utilized an active dynamic sampling technique to measure the δ15N-NH3 values volatilized from maize cropping land in northeast China. These values varied from -38.0 to -0.2‰, with a significantly lower rate-weighted value observed in the early period (May-June, -30.5 ± 6.7‰) as compared with the late period (July-October, -8.5 ± 4.3‰). Seasonal δ15N-NH3 variations were related to the main NH3 production pathway, degree of soil ammonium consumption, and soil environment. Bayesian isotope mixing model analysis revealed that without considering the seasonal δ15N variation in soil-volatilized NH3 could result in an overestimate by up to absolute 38% for agricultural volatile NH3 to regional atmospheric bulk ammonium deposition during July-October, further demonstrating that it is essential to distinguish seasonal δ15N profile of agricultural volatile NH3 in regional source apportionment.

Hemophagocytic lymphohistiocytosis with jaundice as first manifestation: A case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening condition. It is an immune-mediated disease that has a wide range of causes, elicits a hyperinflammatory response, and results in multiple organ damage. Clinical presentations vary, and in some cases, jaundice occurs as the first symptom. CASE SUMMARY: We report the case of a 71-year-old female patient who presented with jaundice. She was admitted to our hospital because of the occurrence of "jaundice for half a month", and upon examination, obstructive jaundice with choledocholithiasis and gallstones was suggested. Cholecystectomy and choledocholithotomy were performed. However, the jaundice did not improve after surgery. We found splenomegaly, cytopenia, hypertriglyceridemia, hypofibrinogenemia, and elevated ferritin. Bone marrow biopsy revealed hemophagocytosis. Later, cardiac arrest occurred when she returned 3 wk after the surgery. We considered that HLH was triggered by septic shock. The patient's condition deteriorated rapidly, with multiple organ dysfunction and severe gastrointestinal bleeding. Corticosteroid therapy and symptomatic treatment failed to save her life. CONCLUSION: Jaundice rarely presents as the first symptom in HLH patients. The HLH in this case was triggered by septic shock with jaundice as the first symptom. Clinicians should try hard to reduce missed diagnoses and misdiagnoses.

A first-in-human phase 1 study of simnotrelvir, a 3CL-like protease inhibitor for treatment of COVID-19, in healthy adult subjects.

Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that can effectively inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the safety, tolerability, and pharmacokinetics of dose escalations of simnotrelvir alone or with ritonavir (simnotrelvir or simnotrelvir/ritonavir) in healthy subjects, as well as the food effect (ClinicalTrials.gov Identifier: NCT05339646). The overall incidence of adverse events (AEs) was 22.2% (17/72) and 6.3% (1/16) in intervention and placebo groups, respectively. The simnotrelvir apparent clearance was 135-369 L/h with simnotrelvir alone, and decreased significantly to 19.5-29.8 L/h with simnotrelvir/ritonavir. The simnotrelvir exposure increased in an approximately dose-proportional manner between 250 and 750 mg when co-administered with ritonavir. After consecutive twice daily dosing of simnotrelvir/ritonavir, simnotrelvir had a low accumulation index ranging from 1.39 to 1.51. The area under the curve of simnotrelvir increased 44.0 % and 47.3 % respectively, after high fat and normal diet compared with fasted status. In conclusion, simnotrelvir has adequate safety and tolerability. Its pharmacokinetics indicated a trough concentration above the level required for 90 % inhibition of SARS-CoV-2 in vitro at 750 mg/100 mg simnotrelvir/ritonavir twice daily under fasted condition, supporting further development using this dosage as the clinically recommended dose regimen.

Characterization of Wei Safflower Seed Oil Using Cold-Pressing and Solvent Extraction.

Wei safflower seed oil (WSO) prepared by the cold pressing method and organic solvent extraction method was characterized in this study. The yield of cold-pressed WSO (CP-WSO) was inferior to that of n-hexane-extracted WSO (HE-WSO). The physicochemical properties (refractive index, density, iodine value, insoluble impurities) and fatty acid compositions were similar, and both were rich in linoleic acid. However, CP-WSO had better color and less solvent residue. The type and content of vitamin E in CP-WSO was also superior to that in HE-WSO, which explained the high oxidative stability of CP-WSO in the Rancimat test. Our results provide a reference for the development of Wei safflower seed oil.

A first-in-human phase I study of SHR-1906, a humanized monoclonal antibody against connective tissue growth factor, in healthy participants.

New therapeutic targets and drugs are urgently needed to halt the fibrosing process in idiopathic pulmonary fibrosis (IPF). SHR-1906 is a novel fully humanized monoclonal antibody against the connective tissue growth factor, which plays an essential role in the genesis of IPF. We assessed the safety, tolerability, pharmacokinetics (PKs), and immunogenicity of single dose SHR-1906 in healthy participants. This was a randomized, double-blind, placebo-controlled, dose-escalation, phase I study. Twelve healthy participants for each dose level were enrolled to receive single ascending doses of SHR-1906 intravenously (1.5, 6, 12, 20, 30, and 45 mg/kg) or placebo and followed for 71 days. The primary end points were safety and tolerability. Treatment-related treatment-emergent adverse events occurred in 25 participants (46.3%) in the SHR-1906 group and 11 (61.1%) in the placebo group. No serious adverse events occurred. Over the dose range investigated, the geometric mean clearance was 0.14-0.63 mL/h/kg, the geometric mean volume of distribution at steady-state was 47.4-75.5 mL/kg, and the terminal elimination half-life was 51.9-349 h. SHR-1906 showed nonlinear PKs. The peak concentration increased in a dose-proportional manner, whereas the area under the concentration-time curve showed a greater than dose-proportional increase. Anti-drug antibodies of SHR-1906 were detected in nine of 54 participants (16.7%). A single dose of SHR-1906 up to 45 mg/kg demonstrated a favorable tolerability profile in healthy participants. The PKs and immunogenicity of SHR-1906 were evaluated, supporting further clinical development.

Supreme laryngeal mask airway for cesarean section under general anesthesia: a 10-year retrospective cohort study.

Background: Previous research showed the use of supraglottic airways in obstetric anesthesia. The relevant evidence of laryngeal mask airway (LMA) on maternal and neonatal outcomes is still limited. We aimed to assess the maternal and neonatal outcomes when the LMA Supreme was used for cesarean section under general anesthesia. Methods: We included all patients who underwent general anesthesia for cesarean section between January 2010 and December 2019. Propensity score matching was used to reduce potential bias from non-random selection of airway intervention. The primary outcome was adverse maternal and neonatal outcomes defined as maternal regurgitation, aspiration, hypoxemia, and low neonatal Apgar scores. Secondary outcomes included patient admission to the intensive care unit, neonate required tracheal intubation, external cardiac massage, and admission to the neonatal intensive care unit. Results: A total of 723 patients were included in the analysis; of whom, 221 received Supreme laryngeal mask airway (LMA group) and 502 were intubated with an endotracheal tube (ETT group). After propensity score matching, 189 patients remained in each group. No episode of regurgitation and aspiration occurred in both groups. There was no difference in the rates of Apgar score below 7 at 1 min (14.3% LMA group vs. 15.3% ETT group, OR 0.931, 95% CI 0.574 to 1.510, P = 0.772) and 5 min (3.7% vs. 4.2%, OR 0.875, 95% CI 0.324 to 2.365, P = 0.792). No difference was observed in the secondary outcomes between the two groups. Conclusion: The LMA Supreme was not associated with higher adverse maternal and neonatal outcomes when compared to an endotracheal tube for cesarean section under general anesthesia. It might be considered an alternative to tracheal intubation in obstetric practice.

Age-related self-DNA accumulation may accelerate arthritis in rats and in human rheumatoid arthritis.

The incidence of rheumatoid arthritis (RA) is increasing with age. DNA fragments is known to accumulate in certain autoimmune diseases, but the mechanistic relationship among ageing, DNA fragments and RA pathogenesis remain unexplored. Here we show that the accumulation of DNA fragments, increasing with age and regulated by the exonuclease TREX1, promotes abnormal activation of the immune system in an adjuvant-induced arthritis (AIA) rat model. Local overexpression of TREX1 suppresses synovial inflammation in rats, while conditional genomic deletion of TREX1 in AIA rats result in higher levels of circulating free (cf) DNA and hence abnormal immune activation, leading to more severe symptoms. The dysregulation of the heterodimeric transcription factor AP-1, formed by c-Jun and c-Fos, appear to regulate both TREX1 expression and SASP induction. Thus, our results confirm that DNA fragments are inflammatory mediators, and TREX1, downstream of AP-1, may serve as regulator of cellular immunity in health and in RA.

Alleviation of Shade Stress in Chinese Yew (Taxus chinensis) Seedlings with 5-Aminolevulinic Acid (ALA).

5-aminolevulinic acid (ALA) is a novel regulator that can promote plant growth, nitrogen uptake, and abiotic stress tolerance. Its underlying mechanisms, however, have not been fully investigated. In this study, the effects of ALA on morphology, photosynthesis, antioxidant systems, and secondary metabolites in two cultivars of 5-year-old Chinese yew (Taxus chinensis) seedlings, 'Taihang' and 'Fujian', were examined under shade stress (30% light for 30 days) using different doses of ALA (0, 30, and 60 mg/L). The findings from our study show that shade stress significantly reduced plant height, stem thickness, and crown width and increased malondialdehyde (MDA) levels. However, the application of 30 mg/L ALA effectively mitigated these effects, which further induced the activity of antioxidant enzymes under shade stress, resulting in the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) being increased by 10%, 16.4%, and 42.1%, and 19.8%, 20.1%, and 42% in 'Taihang' and 'Fujian', respectively. It also promoted their role in the absorption, conversion, and efficient use of light energy. Additionally, the use of 30 mg/L ALA caused a significant increase in the concentration of secondary metabolites, including polysaccharide (PC), carotenoid (CR), and flavonoids (FA), with increases of up to 46.1%, 13.4%, and 35.6% and 33.5%, 7.5%, and 57.5% in both yew cultivars, respectively, contributing to nutrient uptake. With ALA treatment, the yew seedlings showed higher chlorophyll (total chlorophyll, chlorophyll a and b) levels and photosynthesis rates than the seedlings that received the shade treatment alone. To conclude, the application of 30 mg/L ALA alleviated shade stress in yew seedlings by maintaining redox balance, protecting the photorespiratory system, and increasing organic metabolites, thus increasing the number of new branches and shoots and significantly promoting the growth of the seedlings. Spraying with ALA may be a sustainable strategy to improve the shade-resistant defense system of yew. As these findings increase our understanding of this shade stress response, they may have considerable implications for the domestication and cultivation of yew.

CCR2-overexpressing biomimetic carrier-free nanoplatform for enhanced cascade ferroptosis tumor therapy.

Ferroptosis-based nanoplatforms have shown great potential in cancer therapy. However, they also face issues such as degradation and metabolism. Carrier-free nanoplatforms consisting of active drugs can effectively avoid the security issues associated with additional carrier ingredients. Herein, a biomimetic carrier-free nanoplatform (HESN@CM) was designed to treat cancer by modulating cascade metabolic pathways of ferroptosis. CCR2-overexpressing macrophage membrane-modified HESN can target cancer cells via the CCR2-CCL2 axis. The acidic tumor microenvironment (TME) can disrupt the supramolecular interaction of HESN, releasing hemin and erastin. Then, erastin could induce cancer cells ferroptosis by inhibiting system XC- pathways, while hemin, a vital component of blood to transport oxygen, could be broken down by heme oxygenase-1 (HO-1), increasing the intracellular Fe2+ concentration to induce cancer cells' ferroptosis further. Meanwhile, erastin could enhance the activity of HO-1, further promoting the release of Fe2+ from hemin. As a result, HESN@CM demonstrated superior therapeutic efficacy in both primary and metastatic tumors in vitro and in vivo. The carrier-free HESN@CM provided cascade ferroptosis tumor therapy strategies for potential clinical application. STATEMENT OF SIGNIFICANCE: CCR2-overexpressing biomimetic carrier-free nanoplatform (HESN@CM) was designed for cancer treatment by modulating metabolic pathways of ferroptosis. HESN modified with CCR2-overexpressing macrophage membrane can target tumor cells via the CCR2-CCL2 axis. HESN was composed of hemin and erastin without additional vectors. Erastin could directly induce ferroptosis, while hemin could be broken down by heme oxygenase-1 (HO-1), increasing the intracellular Fe2+ concentration to enhance ferroptosis further. Meanwhile, erastin could improve the activity of HO-1, promoting the release of Fe2+ from hemin. Therefore, HESN@CM with good bioavailability, stability, and simple preparation can realize cascade ferroptosis tumor therapy and have the potential prospect of clinical translation.

Low-Power Red Laser Treatment for Anisometropic Myopia Control in Children: A Contralateral Comparison Study.

BACKGROUND: There are some uncertainties about the effect of low-power red laser treatment on myopia control for anisometropic myopia in children. To evaluate the effect and safety of low-power red laser treatment on refractive development for anisometropic myopia in children, a contralateral comparison study was conducted. METHODS: The more myopic eye of child with anisometropic myopia was treated with low-power red laser treatment (LRL group), the other eye received no treatment other than the wearing of single-focus spectacles (SFS) (SFS Group). The LRL treatment was given at home under parental guidance for 3 minutes each time, twice daily with a minimal interval of 4 hours, 7 days per week, using an equipment that produces red laser of 650 nm wavelength at an illuminance range of roughly 1200-1800 lux and an energy of 0.60 mw for a 4-mm pupil (class I classification). RESULTS: Among 51 included children, 44 (86.27%) completed the 3-months study, consisting of 15 girls (34.1%) and 29 boys (65.9%). After 3-months axial length (AL) and spherical equivalent refraction (SER) progression were -0.08 mm [95% CI (confidence interval), 0.11 to 0.06 mm] and +0.23 diopter (D) (95% CI, 0.13-0.33 D) for LRL group and +0.08 mm (95% CI, 0.05-0.11 mm) and -0.07 D (95% CI, -0.16-0.03 D) for SFS group. AL and SER progression between the groups varied by 0.17 mm (95% CI, 0.13-0.20 mm) and -0.30 D (95% CI, -0.42 to -0.18 D). There was no visible structural damage on optical coherence tomography (OCT) scans. CONCLUSIONS: AL growth, myopia progression, and anisometropia of the binoculars can all be slowed down by LRL treatment. Compared to SER progression, axial elongation is more accurate and simpler to monitor. LRL treatment unrecorded functional and structural damage of binoculus.