Penalized weighted smoothed quantile regression for high-dimensional longitudinal data.

Quantile regression, known as a robust alternative to linear regression, has been widely used in statistical modeling and inference. In this paper, we propose a penalized weighted convolution-type smoothed method for variable selection and robust parameter estimation of the quantile regression with high dimensional longitudinal data. The proposed method utilizes a twice-differentiable and smoothed loss function instead of the check function in quantile regression without penalty, and can select the important covariates consistently using the efficient gradient-based iterative algorithms when the dimension of covariates is larger than the sample size. Moreover, the proposed method can circumvent the influence of outliers in the response variable and/or the covariates. To incorporate the correlation within each subject and enhance the accuracy of the parameter estimation, a two-step weighted estimation method is also established. Furthermore, we prove the oracle properties of the proposed method under some regularity conditions. Finally, the performance of the proposed method is demonstrated by simulation studies and two real examples.

Triblock PolyA-Mediated Protein Biosensor Based on a Size-Matching Proximity Hybridization Analysis.

The antibodies in the natural biological world utilize bivalency/multivalency to achieve a higher affinity for antigen capture. However, mimicking this mechanism on the electrochemical sensing interface and enhancing biological affinity through precise spatial arrangement of bivalent aptamer probes still pose a challenge. In this study, we have developed a novel self-assembly layer (SAM) incorporating triblock polyA DNA to enable accurate organization of the aptamer probes on the interface, constructing a "lock-and-key-like" proximity hybridization assay (PHA) biosensor. The polyA fragment acts as an anchoring block with a strong affinity for the gold surface. Importantly, it connects the two DNA probes, facilitating one-to-one spatial proximity and enabling a controllable surface arrangement. By precisely adjusting the length of the polyA fragment, we can tailor the distance between the probes to match the molecular dimensions of the target protein. This design effectively enhances the affinity of the aptamers. Notably, our biosensor demonstrates exceptional specificity and sensitivity in detecting PDGF-BB, as confirmed through successful validation using human serum samples. Overall, our biosensor presents a novel and versatile interface for proximity assays, offering a significantly improved surface arrangement and detection performance.

Biomimetic Nano-Degrader Based CD47-SIRPα Immune Checkpoint Inhibition Promotes Macrophage Efferocytosis for Cardiac Repair.

CD47-SIRPα axis is an immunotherapeutic target in tumor therapy. However, current monoclonal antibody targeting CD47-SIRPα axis is associated with on-target off-tumor and antigen sink effects, which significantly limit its potential clinical application. Herein, a biomimetic nano-degrader is developed to inhibit CD47-SIRPα axis in a site-specific manner through SIRPα degradation, and its efficacy in acute myocardial infarction (AMI) is evaluated. The nano-degrader is constructed by hybridizing liposome with red blood cell (RBC) membrane (RLP), which mimics the CD47 density of senescent RBCs and possesses a natural high-affinity binding capability to SIRPα on macrophages without signaling capacity. RLP would bind with SIRPα and induce its lysosomal degradation through receptor-mediated endocytosis. To enhance its tissue specificity, Ly6G antibody conjugation (aRLP) is applied, enabling its attachment to neutrophils and accumulation within inflammatory sites. In the myocardial infarction model, aRLP accumulated in the infarcted myocardium blocks CD47-SIRPα axis and subsequently promoted the efferocytosis of apoptotic cardiomyocytes by macrophage, improved heart repair. This nano-degrader efficiently degraded SIRPα in lysosomes, providing a new strategy for immunotherapy with great clinical transformation potential.

Cyfluthrin exposure during pregnancy causes neurotoxicity in offspring-Ca2+ overload via IP3R-GRP75-VDAC1 pathway.

Cyfluthrin (Cy) is a widely used pyrethroid insecticide. There is growing evidence that Cy can cause damage to the nervous, reproductive, and immune systems, but there is limited evidence on the potential effects of maternal Cy exposure on offspring. A model of maternal Cy exposure was used to assess its neurobehavioral effects on young-adult offspring. We found that gestational Cy exposure affected pregnancy outcomes and fetal development, and that offspring showed impairments in anxiety as well as learning and memory, accompanied by impairments in hippocampal synaptic ultrastructure and synaptic plasticity. In addition, the IP3R-GRP75-VDAC1 apoptogenic pathway was also upregulated, and in vitro models showed that inhibition of this pathway alleviated neuronal apoptosis as well as synaptic plasticity damage. In conclusion, maternal Cy exposure during pregnancy can cause neurobehavioral abnormalities and synaptic damage in offspring, which may be related to neuronal apoptosis induced by activation of the IP3R-GRP75-VDAC1 pathway in the hippocampus of offspring. Our findings provide clues to understand the neurotoxicity mechanism of maternal Cy exposure to offspring during pregnancy.

Deep learning model to predict lupus nephritis renal flare based on dynamic multivariable time-series data.

OBJECTIVES: To develop an interpretable deep learning model of lupus nephritis (LN) relapse prediction based on dynamic multivariable time-series data. DESIGN: A single-centre, retrospective cohort study in China. SETTING: A Chinese central tertiary hospital. PARTICIPANTS: The cohort study consisted of 1694 LN patients who had been registered in the Nanjing Glomerulonephritis Registry at the National Clinical Research Center of Kidney Diseases, Jinling Hospital from January 1985 to December 2010. METHODS: We developed a deep learning algorithm to predict LN relapse that consists of 59 features, including demographic, clinical, immunological, pathological and therapeutic characteristics that were collected for baseline analysis. A total of 32 227 data points were collected by the sliding window method and randomly divided into training (80%), validation (10%) and testing sets (10%). We developed a deep learning algorithm-based interpretable multivariable long short-term memory model for LN relapse risk prediction considering censored time-series data based on a cohort of 1694 LN patients. A mixture attention mechanism was deployed to capture variable interactions at different time points for estimating the temporal importance of the variables. Model performance was assessed according to C-index (concordance index). RESULTS: The median follow-up time since remission was 4.1 (IQR, 1.7-6.7) years. The interpretable deep learning model based on dynamic multivariable time-series data achieved the best performance, with a C-index of 0.897, among models using only variables at the point of remission or time-variant variables. The importance of urinary protein, serum albumin and serum C3 showed time dependency in the model, that is, their contributions to the risk prediction increased over time. CONCLUSIONS: Deep learning algorithms can effectively learn through time-series data to develop a predictive model for LN relapse. The model provides accurate predictions of LN relapse for different renal disease stages, which could be used in clinical practice to guide physicians on the management of LN patients.

Genetically Engineered Macrophages Co-Loaded with CD47 Inhibitors Synergistically Reconstruct Efferocytosis and Improve Cardiac Remodeling Post Myocardial Ischemia Reperfusion Injury.

Efferocytosis, mediated by the macrophage receptor MerTK (myeloid-epithelial-reproductive tyrosine kinase), is a significant contributor to cardiac repair after myocardial ischemia-reperfusion (MI/R) injury. However, the death of resident cardiac macrophages (main effector cells), inactivation of MerTK （main effector receptor), and overexpression of "do not eat me" signals (brake signals, such as CD47), collectively lead to the impediment of efferocytosis in the post-MI/R heart. To date, therapeutic strategies targeting individual above obstacles are relatively lacking, let alone their effectiveness being limited due to constraints from the other concurrent two. Herein, inspired by the application research of chimeric antigen receptor macrophages (CAR-Ms) in solid tumors, a genetically modified macrophage-based synergistic drug delivery strategy that effectively challenging the three major barriers in an integrated manner is developed. This strategy involves the overexpression of exogenous macrophages with CCR2 (C-C chemokine receptor type 2) and cleavage-resistant MerTK, as well as surface clicking with liposomal PEP-20 (a CD47 antagonist). In MI/R mice model, this synergistic strategy can effectively restore cardiac efferocytosis after intravenous injection, thereby alleviating the inflammatory response, ultimately preserving cardiac function. This therapy focuses on inhibiting the initiation and promoting active resolution of inflammation, providing new insights for immune-regulatory therapy.

Preoperative prognostic nutritional index value as a predictive factor for postoperative delirium in older adult patients with hip fractures: a secondary analysis.

BACKGROUND: Malnutrition is a common geriatric syndrome and can be targeted preoperatively to decrease the risk of postoperative delirium (POD) in older adult patients. To analyze the value of the prognostic nutritional index (PNI) to predict the incidence of POD in older adult patients with hip fractures. METHODS: This was a prospective, observational, cohort study of older adult patients with hip fractures. Preoperative PNI was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/µL) using preoperative laboratory results. Patients were divided into POD and non-POD groups using the Confusion Assessment Method (CAM). The risk factors associated with POD as well as the relationship between PNI values and the incidence of POD were analyzed using univariate and multivariate logistic regression analyses. The predictive value of PNI for POD was assessed using receiver operating characteristic curve analysis. RESULTS: In this cohort of 369 patients who underwent hip fracture surgery, 67 patients (18.2%) were diagnosed with POD by the CAM results. Low PNI increased the risk of POD (odds ratio (OR) = 0.928, 95% confidence interval (CI): 0.864-0.997). General anesthesia (OR = 2.307, 95% CI: 1.279-4.162) and Mini-Mental State Examination (MMSE) score (OR = 0.956, 95% CI: 0.920-0.994) were also identified as risk factors for POD. Receiver operating characteristic curve analysis suggested that PNI combined with the anesthetic method and MMSE score may be used as a potential predictive indicator of POD after hip fracture surgery. CONCLUSION: Preoperative PNI value is related to POD in older adult patients with hip fractures. TRIAL REGISTRATION: This secondary analysis study was approved by the Peking University Third Hospital Medical Science Research Ethics Committee (approval No. M2022578) and registered in the Chinese Clinical Trial Registry (ChiCTR2300070569).

Melatonin regulates the circadian rhythm to ameliorate postoperative sleep disorder and neurobehavioral abnormalities in aged mice.

BACKGROUND: Postoperative sleep disorder (PSD) and delirium, which may be associated with surgery and inhalational anesthetics, induce adverse effects in old adults. Emerging evidence indicates that circadian rhythm contributes to various neuropathological diseases, including Alzheimer's disease. Thus, we analyzed the potential role of circadian rhythm in PSD and delirium-like behavior in aged mice and determined whether exogenous melatonin could facilitate entrainment of the circadian rhythm after laparotomy under sevoflurane anesthesia. METHODS: We selected old C57BL/6J mice which receiving laparotomy/sevoflurane anesthesia as model animals. We employed buried food, open field, and Y maze test to assess delirium-like behavior, and electroencephalography/electromyography (EEG/EMG) were used to investigate sleep changes. We analyzed the transcription rhythm of clock genes in superchiasmatic nucleus (SCN) to explore the effects of surgery and melatonin pretreatment on the circadian rhythm. Then, we measured melatonin receptor levels in SCN and ERK/CREB pathway-related proteins in hippocampus and prefrontal cortex to assess their role in PSDs and delirium-like behavior. RESULTS: Laparotomy under sevoflurane anesthesia had a greater influence than sevoflurane alone, leading to sleep disorder, a shift in sleep-wake rhythm, and delirium-like behavior. Bmal1, Clock, and Cry1 mRNA expression showed a peak shift, MT1 melatonin receptor expression level was increased in the SCN, and p-ERK/ERK and p-CREB/CREB were decreased in hippocampus and prefrontal cortex of aged mice 1 day after laparotomy. Melatonin showed significant efficacy in ameliorating PSD and delirium-like behavior and restoring the circadian rhythm, reversing melatonin receptor and ERK/CREB pathway expression abnormalities. In addition, most of the beneficial effect of melatonin was antagonized by luzindole, a melatonin receptor antagonist. CONCLUSIONS: Melatonin receptors in SCN, circadian rhythm, and ERK/CREB signaling pathway participate in the pathophysiological processes of PSD and delirium-like behavior. Melatonin intervention could be a potential preventative approach for PSD and delirium.

Hippo pathway-manipulating neutrophil-mimic hybrid nanoparticles for cardiac ischemic injury via modulation of local immunity and cardiac regeneration.

The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines. Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules. Here, we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR, fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles (MSNs) loaded with microRNA-10b. The hybrid membrane could endow nanoparticles with strong capacity to migrate into inflammatory sites and neutralize proinflammatory cytokines and increase the delivery efficiency of microRNA-10b into adult mammalian cardiomyocytes (CMs) by fusing with cell membranes and leading to the release of MSNs-miR into cytosol. Upon NM@miR administration, this nanoparticle could home to the injured myocardium, restore the local immunity, and efficiently deliver microRNA-10b to cardiomyocytes, which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-10b. This combination therapy could finally improve cardiac function and mitigate ventricular remodeling. Consequently, this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury.

Scribble deficiency mediates colon inflammation by inhibiting autophagy-dependent oxidative stress elimination.

Scribble is a master scaffold protein in apical-basal polarity. Current knowledge about the biological function of Scribble in colonic epithelial plasticity/regeneration during intestinal inflammation is limited. Here, we showed that the level of Scribble is decreased in inflammatory bowel disease (IBD) patients and mice with DSS-induced colitis. ScribΔIEC mice develops severe acute colitis with disrupted epithelial barrier integrity and impaired crypt stem cell's function. Mechanistically, Scribble suppressed the process of autophagy by modulating the stability of caspase-dependent degradation of Atg16L1 by directly interacting with Atg16L1 in a LRR domain-dependent manner in IECs and led to an accumulation of ROS both in intestinal stem cells and epithelial cells. In addition, further study indicates that dietary sphingomyelin alleviates DSS-induced colitis by increase the expression of Scribble, which suggests that Scribble may be the critical marker of IBD. Our study shows that Scribble deficiency is associated with the dysregulated autophagy and impaired maintenance of colonic stemness, and it may be a target for diagnosis and treatment of IBD.

Antitumor mechanism of Saikosaponin A in the Xiaoying Sanjie Decoction for treatment of anaplastic thyroid cancer by network pharmacology analysis and experiments in vitro and in vivo.

Effective therapies for anaplastic thyroid cancer (ATC) are still limited due to its dedifferentiated phenotype and high invasiveness. Xiaoying Sanjie Decoction (XYSJD), a clinically empirical Chinese medicine compound, has shown positive effects for ATC treatment and recovery. However, the pharmacological mechanisms of effective active compound in XYSJD remain unclear. In this study, we aimed at elucidating the antitumor mechanism of the active compound and identifying the kernel molecular mechanisms of XYSJD against ATC. Firstly, the main chemical constituents of XYSJD were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Then we used network pharmacology and ClusterONE algorithm to analyze the possible targets and pathways of the prescription and active compound Saikosaponin A (SSA). Seven core targets, including P2RY12, PDK1, PPP1CC, PPP2CA, TBK1, ITGB1 and ITGB6, which may be involved in the anti-tumor activity of XYSJD were screened. Finally, using cell biology, molecular biology and experimental zoology techniques, we investigated the mechanism of active compound SSA in the treatment of ATC. The results of qRT-PCR indicated that these seven nuclear targets might play an important role in SSA, the active compound of XYSJD. The combined data provide preliminary study of the pharmacological mechanisms of SSA in XYSJD. SSA may be a promising potential therapeutic and chemopreventive candidate for ATC.

Dual Signal-Enhanced Electrochemiluminescence Strategy Based on Functionalized Biochar for Detecting Aflatoxin B1.

Metal-organic frameworks (MOFs) are often used as carriers in the preparation of electrochemiluminescent (ECL) materials, and ECL materials stabilized in the aqueous phase can be prepared by encapsulating chromophores inside MOFs by an in situ growth method. In this study, nanocomposites MIL-88B(Fe)-NH2@Ru(py)32+ with excellent ECL response were prepared by encapsulating Tris(2,2'-bipyridine)ruthenium dichloride (Ru(py)32+) inside MIL-88B(Fe)-NH2 using the one-step hydrothermal method. MIL-88B(Fe)-NH2 possesses abundant amino groups, which can accelerate the catalytic activation process of K2S2O8, and its abundant pores are also conducive to the enhancement of the transmission rate of co-reactant agents, ions, and electrons, which effectively improves the ECL efficiency. In order to obtain more excellent ECL signals, we prepared aminated biochar (NH2-biochar) using Pu-erh tea dregs as precursor and loaded gold nanoparticles (Au NPs) on its surface as substrate material for modified electrodes. Both NH2-biochar and Au NPs can also be used as a co-reactant promoter to catalyze the activation process of co-reactant K2S2O8. Therefore, a sandwich-type ECL immunosensor was prepared based on a dual signal-enhanced strategy for the highly sensitive and selective detection of aflatoxin B1 (AFB1). Under the optimal experimental conditions, the sensitive detection of AFB1 was achieved in the range of 1 pg·mL-1~100 ng·mL-1 with a detection limit of 209 fg·mL-1. The proposed dual signal-enhanced ECL immunosensor can provide a simple, convenient, and efficient method for the sensitive detection of AFB1 in food and agricultural products.

Double Kissing Inflation Outside the Stent Versus Jailed Balloon Technique for Coronary Bifurcation Lesions.

Side branch (SB) occlusion remains challenging in bifurcation percutaneous coronary intervention. We have introduced a novel method to protect SB named double kissing inflation outside the stent (DKo), which features twice inflation of protective balloon kissing with stent and postdilation balloon. This study compared protective effects of DKo vs jailed balloon technique (JBT) for bifurcation. This retrospective, single-center study enrolled 875 consecutive bifurcation lesions receiving either DKo (n = 209) or JBT (n = 666). At the 12-month follow-up, major adverse cardiac event occurred less in DKo (6.7% vs 12.0%; P = 0.042), even in 1:2 propensity score matching analysis (6.4% vs 12.3%; P = 0.034). Rewiring and transient SB loss occurred also less in DKo (0.5% vs 13.8% [P < 0.001]; 0.5% vs 4.8% [P = 0.003]). Similar results were observed in matching analysis. This study demonstrated DKo protected SB better than JBT in bifurcation percutaneous coronary intervention.

BOston Neonatal Brain Injury Dataset for Hypoxic Ischemic Encephalopathy (BONBID-HIE): Part I. MRI and Manual Lesion Annotation.

Hypoxic ischemic encephalopathy (HIE) is a brain injury that occurs in 1 ~ 5/1000 term neonates. Accurate identification and segmentation of HIE-related lesions in neonatal brain magnetic resonance images (MRIs) is the first step toward predicting prognosis, identifying high-risk patients, and evaluating treatment effects. It will lead to a more accurate estimation of prognosis, a better understanding of neurological symptoms, and a timely prediction of response to therapy. We release the first public dataset containing neonatal brain diffusion MRI and expert annotation of lesions from 133 patients diagnosed with HIE. HIE-related lesions in brain MRI are often diffuse (i.e., multi-focal), and small (over half the patients in our data having lesions occupying <1% of brain volume). Segmentation for HIE MRI data is remarkably different from, and arguably more challenging than, other segmentation tasks such as brain tumors with focal and relatively large lesions. We hope that this dataset can help fuel the development of MRI lesion segmentation methods for HIE and small diffuse lesions in general.

Metabolomic analysis identifies the regulation of lipid metabolism pathway as potential mechanisms of Jiangzhi decoction against non-alcoholic fatty liver disease.

OBJECTIVES: To illustrate the metabolic regulatory mechanisms of Jiangzhi decoction (JZD) against non-alcoholic fatty liver disease (NAFLD). METHODS: High-fat diet (HFD)-induced NAFLD rats were treated with JZD. The pathological morphology, lipid indexes and liver function were detected. Metabolic profiles were examined by liquid chromatography-mass spectrometry (LC-MS). Multivariate and univariate statistical analysis were used to search the differential metabolites. Pathway enrichment analysis was carried out using Kyoto Encyclopedia of Genes and Genomes database. Compound-gene networks were built by Cytoscape software. RESULTS: JZD significantly alleviated the pathological conditions and improved lipid index levels. Multivariate analysis showed a good separation among different groups. Three hundred and twenty-seven metabolites in HFD versus control and 301 metabolites in JZD versus HFD were identified to be significantly different. Pathway enrichment analysis showed that lipid metabolism pathways were prominent altered pathways. Importantly, the relationships were more distant between JZD and HFD groups in all five lipid metabolism pathways, including arachidonic acid metabolism, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism and sphingolipid metabolism, while those were obviously closer between JZD and control groups. Simultaneously, JZD treatment restored the levels of disturbed differential metabolites in HFD group. CONCLUSION: JZD had an effect on alleviating NAFLD via regulating relevant lipid metabolism.

Reciprocal interaction between mitochondrial fission and mitophagy in postoperative delayed neurocognitive recovery in aged rats.

INTRODUCTION: Emerging evidence suggests that mitochondrial dysfunction plays a crucial role in the pathogenesis of postoperative delayed neurocognitive recovery (dNCR). Mitochondria exist in a dynamic equilibrium that involves fission and fusion to regulate morphology and maintains normal cell function via the removal of damaged mitochondria through mitophagy. Nonetheless, the relationship between mitochondrial morphology and mitophagy, and how they influence mitochondrial function in the development of postoperative dNCR, remains poorly understood. Here, we observed morphological alterations of mitochondria and mitophagy activity in hippocampal neurons and assessed the involvement of their interaction in dNCR following general anesthesia and surgical stress in aged rats. METHODS: Firstly, we evaluated the spatial learning and memory ability of the aged rats after anesthesia/surgery. Hippocampal mitochondrial function and mitochondrial morphology were detected. Afterwards, mitochondrial fission was inhibited by Mdivi-1 and siDrp1 in vivo and in vitro separately. We then detected mitophagy and mitochondrial function. Finally, we used rapamycin to activate mitophagy and observed mitochondrial morphology and mitochondrial function. RESULTS: Surgery impaired hippocampal-dependent spatial learning and memory ability and caused mitochondrial dysfunction. It also increased mitochondrial fission and inhibited mitophagy in hippocampal neurons. Mdivi-1 improved mitophagy and learning and memory ability of aged rats by inhibiting mitochondrial fission. Knocking down Drp1 by siDrp1 also improved mitophagy and mitochondrial function. Meanwhile, rapamycin inhibited excessive mitochondrial fission and improved mitochondrial function. CONCLUSION: Surgery simultaneously increases mitochondrial fission and inhibits mitophagy activity. Mechanistically, mitochondrial fission/fusion and mitophagy activity interact reciprocally with each other and are both involved in postoperative dNCR. These mitochondrial events after surgical stress may provide novel targets and modalities for therapeutic intervention in postoperative dNCR.

Prussian Blue Nanozyme Treatment of Ischemic Brain Injury via Reducing Oxidative Stress Inhibits Inflammation, Suppresses Apoptosis, and Promotes Neurological Recovery.

Ischemic stroke is one of the leading causes of death and severe disability. The overproduction of reactive oxygen species (ROS) after ischemic injury causes a series of inflammatory reactions, which is considered to be the key factor in aggravating brain injury. However, the current clinical drug treatment effect is not satisfactory. Therefore, ROS scavengers that can remove excess ROS production have great therapeutic potential. Nanoenzymes with potent antioxidant stress and anti-inflammatory properties have the potential to treat ischemic stroke. Herein, we used a Prussian blue nanoenzyme (PBzyme) to study the treatment of ischemic stroke. The comprehensive effects of PBzyme on ROS in vivo and in vitro were investigated. Pbzyme inhibited the activation of macrophages and the release of inflammatory factors in the brain, promoted the polarization of microglia to M2, inhibited neuronal apoptosis, and promoted the recovery of neurological function after ischemic stroke. This research may provide a promising application for nanoenzymes to treat brain diseases.

Diazabicyclic Electroactive Ionenes for Efficient and Stable Organic Solar Cells.

Electroactive ionenes combining caged-shaped diazabicyclic cations and aromatic diimides were developed as interlayers in organic solar cells (OSCs). These ionenes reduce the work-function of air-stable metal electrodes (e.g., Ag, Cu and Au) by generating strong interfacial dipoles, and their optoelectronic and morphological characters can be modulated by aromatic diimides, leading to high conductivity and good compatibility with active layers. The optimal ionene exhibits superior charge-transport, desirable crystallinity, and weak visible-absorption, boosting the efficiency of benchmark PM6 : Y6-based OSCs up to 17.44 %. The corresponding normal devices show excellent stability at maximum power point test under one sun illumination for 1000 h. Replacing Y6 with L8-BO promotes the efficiency to 18.43 %, one of the highest in binary OSCs. Notably, high efficiencies >16 % are maintained as the interlayer thickness increasing to 105 nm, the best result with interlayer-thickness over 100 nm.

Interaction of methionine sulfoxide reductase B5 with SlMYC2 stimulates the transcription of MeJA-mediated autophagy-related genes in tomato fruit.

Methyl jasmonate (MeJA) has been shown to induce autophagy in various plant stress responses and metabolic pathways. MYC2 is involved in MeJA-mediated postharvest fruit biological metabolism, but it is unclear how it affects MeJA-induced fruit autophagy. In this study, we noticed that silencing SlMYC2 significantly reduced the increase in autophagy-related genes (SlATGs) expression induced by MeJA. SlMYC2 could also bind to the promoters of several SlATGs, including SlATG13a, SlATG13b, SlATG18a, and SlATG18h, and activate their transcript levels. Moreover, SlMsrB5, a methionine sulfoxide reductase, could interact with SlMYC2. Methionine oxidation in SlMYC2 and mimicking sulfoxidation in SlMYC2 by mutation of methionine-542 to glutamine reduced the DNA-binding ability and transcriptional activity of SlMYC2, respectively. SlMsrB5 partially repaired oxidized SlMYC2 and restored its DNA-binding ability. On the other hand, silencing SlMsrB5 inhibited the transcript levels of SlMYC2-targeted genes (SlATG13a, SlATG13b, SlATG18a, and SlATG18h). Similarly, dual-luciferase reporter (DLR) analysis revealed that SlMsrB5-SlMYC2 interaction significantly increased the ability of SlMYC2-mediated transcriptional activation of SlATG13a, SlATG13b, SlATG18a, and SlATG18h. These findings demonstrate that SlMsrB5-mediated cyclic oxidation/reduction of methionine in SlMYC2 influences SlATGs expression. Collectively, these findings reveal the mechanism of SlMYC2 in SlATGs transcriptional regulation, providing insight into the mechanism of MeJA-mediated postharvest fruit quality regulation.