Structure-Guided Discovery and Preclinical Assessment of Novel (Thiophen-3-yl)aminopyrimidine Derivatives as Potent ERK1/2 Inhibitors.

The RAS-RAF-MEK-ERK signaling cascade is abnormally activated in various tumors, playing a crucial role in mediating tumor progression. As the key component at the terminal stage of this cascade, ERK1/2 emerges as a potential antitumor target and offers a promising therapeutic strategy for tumors harboring BRAF or RAS mutations. Here, we identified 36c with a (thiophen-3-yl)aminopyrimidine scaffold as a potent ERK1/2 inhibitor through structure-guided optimization for hit 18. In preclinical studies, 36c showed powerful ERK1/2 inhibitory activities (ERK1/2 IC50 = 0.11/0.08 nM) and potent antitumor efficacy both in vitro and in vivo against triple-negative breast cancer and colorectal cancer models harboring BRAF and RAS mutations. 36c could directly inhibit ERK1/2, significantly block the phosphorylation expression of their downstream substrates p90RSK and c-Myc, and induce cell apoptosis and incomplete autophagy-related cell death. Taken together, this work provides a promising ERK1/2 lead compound for multiple tumor-treatment drug discovery.

SEB-YOLO: An Improved YOLOv5 Model for Remote Sensing Small Target Detection.

Due to the limited semantic information extraction with small objects and difficulty in distinguishing similar targets, it brings great challenges to target detection in remote sensing scenarios, which results in poor detection performance. This paper proposes an improved YOLOv5 remote sensing image target detection algorithm, SEB-YOLO (SPD-Conv + ECSPP + Bi-FPN + YOLOv5). Firstly, the space-to-depth (SPD) layer followed by a non-strided convolution (Conv) layer module (SPD-Conv) was used to reconstruct the backbone network, which retained the global features and reduced the feature loss. Meanwhile, the pooling module with the attention mechanism of the final layer of the backbone network was designed to help the network better identify and locate the target. Furthermore, a bidirectional feature pyramid network (Bi-FPN) with bilinear interpolation upsampling was added to improve bidirectional cross-scale connection and weighted feature fusion. Finally, the decoupled head is introduced to enhance the model convergence and solve the contradiction between the classification task and the regression task. Experimental results on NWPU VHR-10 and RSOD datasets show that the mAP of the proposed algorithm reaches 93.5% and 93.9%respectively, which is 4.0% and 5.3% higher than that of the original YOLOv5l algorithm. The proposed algorithm achieves better detection results for complex remote sensing images.

Direct and Indirect Longitudinal Associations of Mother and Father Engagement in Middle Childhood on Adolescent Externalizing and Internalizing Behaviors.

Parent engagement is an important aspect of parenting during childhood. However, little is known about the unique longitudinal associations of mother and father engagement with adolescents' externalizing and internalizing problem behaviors. This study uses Future of Families and Child Wellbeing Study data to examine the potential direct and indirect associations of parent engagement at age 9 on adolescent externalizing and internalizing behaviors at age 15. The analytic sample size is 1349, and at age 9, the mean age of children was 9.40 years (SD = 0.37). Forty-eight percent of children were female and 68% of them were from the married families. The results show that while controlling for mother engagement, higher father engagement at age 9 was directly associated with fewer adolescent internalizing behaviors, only among adolescent boys and in married families. In addition, among adolescent boys, father engagement had an indirect association with externalizing behaviors through father-child closeness. Mother engagement, however, is only found to have an indirect association with adolescents' externalizing and internalizing behaviors through maternal hostility (while controlling for father engagement). The results for mother engagement held for boys and in married families only. The findings indicate that both mother and father engagement during childhood is important and helpful to prevent adolescent problem behaviors directly or indirectly via parent-child relationship.

Genomic characterization and pathogenicity of a novel fowl adenovirus serotype 11 isolated from chickens with inclusion body hepatitis in China.

Fowl adenovirus serotype 11 (FAdV-11) is one of the primary causative agents of inclusion body hepatitis (IBH), which causes substantial economic losses in the world poultry industry. In this study, we characterized the genome of the fowl adenovirus serotype 11 (FAdV-11) isolate FJSW/2021. The full genome of FJSW/2021 was 44, 154 base pairs (bp) in length and had a similar organization to that of previously reported FAdV-11 isolates. Notably, compared with those of other reported FAdV-11 strains, the preterminal protein (pTP) of FAdV-11 FJSW/2021 has six amino acid (aa) insertions (S-L-R-I-I-C) between 470 and 475 and one aa mutation of L476F; moreover, the tandem repeat (TR) regions of TR1 and TR2 were 33 bp (1 repeat) and 1,080 bp (8 repeats) shorter than those of the Canadian nonpathogenic isolate ON NP2, respectively. The pathogenicity of FJSW/2021 was studied in 10-day-old specific pathogen-free chicken embryos following allantoic cavity inoculation and in 1-day-old, 1-wk-old and 2-wk-old SPF chickens following intramuscular inoculation with 107 TCID50 of the virus. The results showed that FJSW/2021 can induce typical severe IBH in chicks less than 2 wk old. These findings highlighted the genetic differences between the pathogenic and non-pathogenic FAdV-11 isolates. The data will provide guidance for identifying the virulence factors of FAdV-11 strains. The animal challenge model developed in our study will allow precise evaluation of the efficacy of potential FAdV-11 vaccine candidates.

Mechanism of salidroside regulating autophagy based on network pharmacology and molecular docking.

Salidroside is a natural product of phenols with a wide range of pharmacological functions, but whether it plays a role in regulating autophagy is unclear. We systematically investigated the regulatory effect and molecular mechanism of salidroside on autophagy through network pharmacology, which provided a theoretical basis for subsequent experimental research. First, the target genes of salidroside were obtained using the Chinese Medicine System Pharmacology Database and Analysis Platform, and the target genes were converted into standardized gene names using the Uniprot website. At the same time, autophagy-related genes were collected from GeneCards, and preliminary handling of data to obtain intersecting genes. Then, the String website was used to construct a protein-protein interaction network, and to perform the Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis. To observe the specific molecular mechanism by which salidroside regulates autophagy, we constructed a drug component-target genes-autophagy network. Finally, we performed molecular docking to verify the possible binding conformation between salidroside and the candidate target. By searching the database and analyzing the data, we found that 113 target genes in salidroside interact with autophagy. Salidroside regulate autophagy in relation to a number of important oncogenes and signaling pathways. Molecular docking confirmed that salidroside has high affinity with mTOR, SIRT1, and AKT1. Through network pharmacology combined with molecular docking-validated research methods, we revealed the underlying mechanism of salidroside regulation of autophagy. This study not only provides new systematic insights into the underlying mechanism of salidroside in autophagy, but also provides new ideas for network approaches for autophagy-related research.

Analysis of physical activity and prescription opioid use among US adults: a cross-sectional study.

BACKGROUND: Opioid crisis has become a global concern, but whether physical activity (PA) can effectively reduce prescription opioid use remains unclear. The study aimed to examine the relationship of different domains of PA (e.g., occupation-related PA [OPA], transportation-related PA [TPA], leisure-time PA [LTPA]) with prescription opioid use and duration of prescription opioid use. METHODS: This cross-sectional study was conducted on 27,943 participants aged ≥ 18 years from National Health and Nutrition Examination Survey (NHANES, 2007- March 2020). We examined the relationship of different domains of PA with prescription opioid use and duration of prescription opioid use using multivariable logistic regression. Stratified analysis and a series of sensitivity analysis were used to elevate robustness. All analyses were conducted using appropriate sampling weights. RESULTS: Of the 27,943 participants, the mean age was 45.10 years, with 14,018 [weighted, 50.0%] females and 11,045 [weighted, 66.0%] non-Hispanic White. After multivariable adjustment, inverse associations between PA and prescription opioid use were observed for sufficient (≥ 150 min/week) total PA (OR,0.68 95%CI [0.56-0.81]), TPA (OR,0.73 95%CI [0.58-0.92]), and LTPA (OR,0.60 95%CI [0.48-0.75]) compared with insufficient PA(< 150 min/week), but not for sufficient OPA (OR,0.93 95%CI [0.79-1.10]). In addition, the associations were dose-responsive, participants had 22-40%, 27-36%, and 26-47% lower odds of using prescription opioids depending on the duration of total PA, TPA, and LTPA, respectively. Nevertheless, the impact of PA on prescription opioid use varied by duration of opioid use. Sufficient total PA was associated with elevated odds of short-term use of prescription opioids (< 90 days). Comparatively, sufficient total PA, TPA, and LTPA had different beneficial effects on reducing long-term use of prescription opioids (≥ 90 days) depending on the strength of opioids. CONCLUSIONS: This study demonstrated sufficient total PA, TPA, and LTPA were inversely associated with prescription opioid use and varied depending on the duration and strength of prescription opioid use. These findings highlight PA can provide policy guidance to address opioid crisis.

Selective removal of thallium from water by MnO2-doped magnetic beads: Performance and mechanism study.

Aqueous thallium has posed an increasing threat to environment as human's intensified activities in mining, refining, process and discharge. Remediation on thallium pollution has been of up-most importance to water treatment. In present work, MnO2 and magnetic Fe3O4 have been implanted to sodium alginate (SA) in presence of carboxyl methyl cellulose (CMC), and the resultant beads consisted of SA/CMC/MnO2/Fe3O4 were characterized. The materials were applied to treatment of Tl-contaminated water as adsorbent in lab. The removal results revealed that the adsorption capacity reached 38.8 mg (Tl)·g (beads)-1 and almost 100 % removal efficiency was achieved. The residual Tl was below 0.1 µg·L-1, meeting the discharge standard regulated in China. The kinetic adsorption was better described as a pseudo-second-order and three-step intra-particle diffusion model. Freundlich isotherm was well fitted the experimental data. The absorbent shown an excellent competitive specificity (KTl/M: ∼104!) over common hazardous ions Cu2+, Cd2+, Co2+, Pb2+ and Cr3+, as well as naturally abundant K+ and Na+ (KTl/M: 10-102) in mimic environmental conditions. Regeneration and reusability of the absorbent was also verified by five absorption-desorpotion cycles. XPS results revealed that a redox reaction between Mn4+ with Tl+, and an ion exchange of H+ (-O-Fe) and Tl+ were assumed to be main process for the specific capturing. This study provided an efficient SA/CMC/MnO2/Fe3O4 composite beads that could be a promising adsorbent for Tl-polluted water treatment.

Lily (Lilium spp.) LhERF4 negatively affects anthocyanin biosynthesis by suppressing LhMYBSPLATTER transcription.

Anthocyanins are among the main pigments involved in the colouration of Asiatic hybrid lily (Lilium spp.). Ethylene, a plant ripening hormone, plays an important role in promoting plant maturation and anthocyanin biosynthesis. However, whether and how ethylene regulates anthocyanin biosynthesis in lily tepals have not been characterized. Using yeast one-hybrid screening, we previously identified an APETALA2 (AP2)/ETHYLENE RESPONSE FACTOR (ERF) named LhERF4 as a potential inhibitor of LhMYBSPLATTER-mediated negative regulation of anthocyanin biosynthesis in lily. Here, transcript and protein analysis of LhERF4, a transcriptional repressor, revealed that LhERF4 directly binds to the promoter of LhMYBSPLATTER. In addition, overexpression of LhERF4 in lily tepals negatively regulates the expression of key structural genes and the total anthocyanin content by suppressing the LhMYBSPLATTER gene. Moreover, the LhERF4 gene inhibits anthocyanin biosynthesis in response to ethylene, affecting anthocyanin accumulation and pigmentation in lily tepals. Collectively, our findings will advance and elucidate a novel regulatory network of anthocyanin biosynthesis in lily, and this research provides new insight into colouration regulation.

Design, Synthesis, and Biological Evaluation of Dual Inhibitors of EGFRL858R/T790M/ACK1 to Overcome Osimertinib Resistance in Nonsmall Cell Lung Cancers.

Activation of the alternative pathways and abnormal signaling transduction are frequently observed in third-generation EGFR-TKIs (epidermal growth factor receptor tyrosine kinase inhibitors)-resistant patients. Wherein, hyperphosphorylation of ACK1 contributes to EGFR-TKIs acquired resistance. Dual inhibition of EGFRL858R/T790M and ACK1 might improve therapeutic efficacy and overcome resistance in lung cancers treatment. Here, we identified a EGFRL858R/T790M/ACK1 dual-targeting compound 21a with aminoquinazoline scaffold, which showed excellent inhibitory activities against EGFRL858R/T790M (IC50 = 23 nM) and ACK1 (IC50 = 263 nM). The cocrystal and docking analysis showed that 21a occupied the ATP binding pockets of EGFRL858R/T790M and ACK1. Moreover, 21a showed potent antiproliferative activities against the H1975 cells, MCF-7 cells and osimertinib-resistant cells AZDR. Further, 21a showed significant antitumor effects and good safety in ADZR xenograft-bearing mice. Taken together, 21a was a potent dual inhibitor of EGFRL858R/T790M/ACK1, which is deserved as a potential lead for overcoming acquired resistance to osimertinib during the EGFR-targeted therapy.

First Report of Fusarium proliferatum Causing Bulb Rot on Lilium davidii var. willmottiae in China.

Lilium davidii var. willmottiae, known as Lanzhou lily, is widely cultivated in China for its edible bulbs. In July 2023, symptoms of bulb rot were observed on Lanzhou lilies harvested from Lanzhou, Gansu Province, during storage at the Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences (Beijing, China), at an incidence of nearly 70%. The surface of the lily scales had dark water-stained spots, after the development of which the color gradually darkened, the bulbs became soft, accompanied by a pungent smell. Finally, the whole bulb became ruined and rotten, and there were thick mycelium layers on the bulbs. The infected bulbs were washed with clean water, sterilized with 75% ethanol for 30 s and 2% sodium hypochlorite for 5 min, and then rinsed three times with sterile distilled water. The 5 mm×5 mm tissue pieces from the junction of the diseased part and the healthy part were clipped, placed on potato dextrose agar (PDA) medium and subsequently incubated at 25 °C. Pure cultures were obtained by transferring hyphal tips to new PDA plates. A total of 10 fungal isolates were obtained, all of which exhibited typical Fusarium characteristics. The colonies were white to pink with white to cream-colored aerial mycelia. After 10 to 15 days of incubation, the macroconidia (n = 50) were hyaline, relatively slender with a curve, three to five septate, and 8.73 to 33.24 × 2.16 to 4.19 µm in length. The microconidia (n = 50) were hyaline and pyriform, without septa, and measured 4.04 to 8.48 × 1.24 to 2.65 µm. These morphological characteristics were similar to those described for Fusarium proliferatum (Leslie and Summerell 2006). For molecular identification, a cetyltrimethylammonium bromide (CTAB) protocol was used to extract total genomic DNA (O'Donnell et al., 1998), after which the internal transcribed spacer (ITS), translation elongation factor subunit 1-alpha (TEF1-α) and RNA polymerase Ⅱ subunit 2 (RPB2) genes were amplified using the universal primers ITS1/ITS4, EF1/EF2 and RPB2-5f2/fRPB2-7cr, respectively, and subsequently sequenced (White et al., 1990; O'Donnell et al., 1998; Liu et al., 1999; Reeb et al., 2004; O'Donnell et al., 2007; Jiang et al., 2018). The sequences of a representative isolate (CAAS01) were analyzed and submitted to GenBank under accession numbers OR554007 (ITS), OR594233 (TEF1-α) and OR603932 (RPB2). A BLAST analysis revealed that the sequences of the ITS, TEF1-α, and RPB2 genes shared 100%, 100%, and 100% identity, respectively, with those of Fusarium proliferatum (MT466521.1, MK952792.1, and LT841266.1) in GenBank. In addition, the ITS, TEF1-α and RPB2 sequences shared 100%, 100%, and 100% identity with those of Fusarium annulatum (LC13675, the Fusarium fujikuroi species complex; previously known as the Gibberella fujikuroi species complex) in the Fusarium-ID database. Fusarium proliferatum, whose common synonyms are Gibberella fujikuroi mating population D and Gibberella fujikuroi var. intermedia, is the anamorphic form of the Gibberella fujikuroi complex that belongs to the Nectriaceae family. A phylogenetic tree was constructed based on the combined TEF1-α and RPB2 sequences of CAAS01 and other Fusarium isolates, revealing that CAAS01 was grouped with Fusarium proliferatum. Based on sequence alignment and phylogenetic analysis, the isolate was identified as Fusarium proliferatum. To determine the pathogenicity of the isolated fungi, healthy bulbs were punctured with disposable sterilized needles and soaked in equal amounts of sterile water and conidial suspension (1×107 conidia/mL) for 30 min respectively. The pathogenicity experiment was repeated three times. After 7 days of inoculation at 25 °C and 80% relative humidity, the surface of the inoculated bulbs produced water-stained spots and mycelium layers consistent with the symptoms exhibited by Lilium davidii var. willmottiae bulbs during storage, while the uninoculated lily bulbs remained symptomless. Fusarium proliferatum was reisolated from the infected bulbs and identified based on morphological and molecular characteristics, fulfilling Koch's postulates. To our knowledge, this is the first report of bulb rot on Lilium davidii var. willmottiae caused by Fusarium proliferatum in China. This study will contribute to the development of management strategies for this postharvest disease in Lilium davidii var. willmottiae.

Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis.

OBJECTIVE: This study aimed to investigate the clinicopathological features and prognostic indicators of alveolar soft part sarcoma (ASPS). METHODS: The characteristics of 26 ASPS patients diagnosed at our hospital between January 2011 and January 2019 were retrospectively analysed. RESULTS: The data for 12 male and 14 female patients, with a median age of 27.5 years, were assessed. The clinical symptoms mainly included painless enlarged masses in deep soft tissues. ASPS had a characteristic pathological morphology. Twenty-four patients were positive for TFE3, and TFE3 gene rearrangement was detected in 12 patients. Among the 26 patients who completed follow-up, 14 had metastasis, 1 had local recurrence, and 7 died. Kaplan-Meier survival analysis revealed that prognosis was significantly correlated with sex, tumour size and metastasis (P < 0.05). Multivariate Cox regression analysis revealed that sex and metastasis were independent prognostic risk factors for patients with ASPS (P < 0.05). CONCLUSION: ASPS is a rare soft tissue sarcoma of unknown origin that occurs in young people, has a slow but metastatic course, and is associated with a poor 5-year survival rate among patients with metastasis. ASPS has character TFE3 protein and gene expression, and the diagnosis is relatively specific. The diagnosis requires comprehensive analysis of clinical history, histological morphology, and immunohistochemistry.

Automated pancreatic segmentation and fat fraction evaluation based on a self-supervised transfer learning network.

Accurate segmentation of the pancreas from abdominal computed tomography (CT) images is challenging but essential for the diagnosis and treatment of pancreatic disorders such as tumours and diabetes. In this study, a dataset with 229 sets of high-resolution CT images was generated and annotated. We proposed a novel 3D segmentation model named nnTransfer (nonisomorphic transfer learning) net, which employs generative model structure for self-supervision to facilitate the network's learning of image attributes from unlabelled data. The effectiveness for pancreas segmentation of nnTransfer was assessed using the Hausdorff distance (HD) and Dice similarity coefficient (DSC) on the dataset. Additionally, a histogram analysis with local thresholding was used to achieve automated whole-volume measurement of pancreatic fat (fat volume fraction, FVF). The proposed technique performed admirably on the dataset, with DSC: 0.937 ± 0.019 and HD: 2.655 ± 1.479. The mean pancreas volume and FVF of the pancreas were 91.95 ± 23.90 cm3 and 12.67 % ± 9.84 %, respectively. The nnTransfer functioned flawlessly and autonomously, facilitating the use of the FVF to evaluate pancreatic disease, particularly in patients with diabetes.

Changes in the structure and functional properties of soybean isolate protein: Effects of different modification methods.

Soybean protein isolate (SPI) is an important plant protein in food processing; however, its spherical structure prevents the exposure of its hydrophobic residues and affects its functional properties. In this study, we elucidate the effects of deamidation, phosphorylation, and glycosylation on the structure (Fourier-transform infrared spectroscopy, circular dichroism, fluorescence, and scanning electron microscopy) and functional properties (solubility, emulsifying activity index (EAI), and emulsifying stability index (ESI)) of SPI. The zeta potentials of the deamidated, phosphorylated, and glycosylated (DSPI, PSPI, and MSPI, respectively) samples decreased significantly (p < 0.05) relative to those of SPI. The functional properties of the modified SPI samples were improved, with MSPI-2 showing the best solubility (86.73 ± 0.34%), EAI (118.89 ± 0.73 m2/g), and ESI (273.33 ± 0.59 min). Moreover, the effects of the three modifications on the SPI functional properties increase in the order MSPI > PSPI > DSPI. These results provide a theoretical understanding the relationship between the modifications and SPI structure.

Efficient Tin-Based Perovskite Solar Cells Enabled by Precisely Synthesized Single-Isomer Fullerene Bisadducts with Regulated Molecular Packing.

Designing and synthesizing fullerene bisadducts with a higher-lying conduction band minimum is promising to further improve the device performance of tin-based perovskite solar cells (TPSCs). However, the commonly obtained fullerene bisadduct products are isomeric mixtures and require complicated separation. Moreover, the isomeric mixtures are prone to resulting in energy alignment disorders, interfacial charge loss, and limited device performance improvement. Herein, we synthesized single-isomer C60- and C70-based diethylmalonate functionalized bisadducts (C60BB and C70BB) by utilizing the steric-hindrance-assisted strategy and determined all molecular structures involved by single crystal diffraction. Meanwhile, we found that the different solvents used for processing the fullerene bisadducts can effectively regulate the molecular packing in their films. The dense and amorphous fullerene bisadduct films prepared by using anisole exhibited the highest electron mobility. Finally, C60BB- and C70BB-based TPSCs showed impressive efficiencies up to 14.51 and 14.28%, respectively. These devices also exhibited excellent long-term stability. This work highlights the importance of developing strategies to synthesize single-isomer fullerene bisadducts and regulate their molecular packing to improve TPSCs' performance.

Adult localized Langerhans cell histiocytosis: A case report.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare clonal proliferative disease of Langerhans cells with unknown pathogenesis. An increasing number of clinicians recognize that LCH has a wide clinical spectrum and a highly varied course. Adults rarely develop LCH. Here, we report a case of adult localized LCH. CASE SUMMARY: A 32-year-old woman presented with plaques and ulcers on the vulva and crissum, accompanied by pain that persisted for more than one year. Physical examination revealed a red-infiltrating plaque with ulcerations and exudates in the vulva and crissum. Pathological examination revealed a diffuse infiltration of lymphocytes, eosinophilic granulocytes, and histiocytoid cells in the superficial dermis. Proliferative histiocytoid cells showed mild atypia, partly with kidney-shaped nuclei. Immunohistochemical examination showed that the histiocytoid cells were positive for S100 protein and CD1 and weakly positive for CD68 (20% +), with a Ki-67 index of 30%. Laboratory tests did not reveal any other systemic damage. The patient was diagnosed with adult localized LCH and was prescribed oral prednisone (20 mg) once daily. The skin lesions gradually improved and are still being followed-up. CONCLUSION: Adult localized LCH is rare and must be differentiated from other common conditions.

Association between secondhand smoke exposure and severe headaches or migraine in never-smoking adults.

OBJECTIVE: The study aimed to examine the relationship between secondhand smoke (SHS) exposure and severe headaches or migraine in never-smoking adults verified by serum cotinine. BACKGROUND: Current evidence about the association between self-reported SHS exposure and headaches or migraine is limited and contradictory. An important issue lies in the lack of actual SHS exposure assessment through biomarkers. METHODS: We conducted a cross-sectional study on 4560 never-smoking adults from the National Health and Nutrition Examination Survey (NHANES), 1999-2004. The SHS exposure was evaluated by measuring serum cotinine concentrations. The information regarding severe headaches or migraine was based on self-reporting. RESULTS: The overall prevalence rate of severe headaches or migraine was 20% (919/4560). After adjusting for relevant covariates, we found that heavy SHS exposure (serum cotinine at 1 to 10 ng/mL) was positively associated with severe headaches or migraine (OR: 2.02, 95% CI [1.19, 3.43]); however, no significant association was found between low SHS exposure (serum cotinine at 0.05 to 0.99 ng/mL) and severe headaches or migraine (OR: 1.15, 95% CI [0.91, 1.47]). Restricted cubic spline analysis showed that the natural logarithm of serum cotinine had a linear relationship with severe headaches or migraine (p = 0.335 for nonlinearity). Stratified analysis indicated that individuals with a BMI of <25 (p < 0.001 for interaction) and sedentary activity (p = 0.016 for interaction) modified the relationship between SHS exposure and severe headaches and migraine. Even after altering the definition of SHS exposure, excluding drugs that might affect the metabolism of serum cotinine, and multiple imputation, our sensitivity analysis results remained stable. CONCLUSIONS: The study demonstrated that heavy SHS exposure (serum cotinine at 1 to 10 ng/mL) had a significant positive association with severe headaches or migraine in never-smoking adults. Prospective studies are necessary to verify this relationship in the future.

Single-case design meta-analyses in education and psychology: a systematic review of methodology.

Meta-analysis is of increasing importance as this quantitative synthesis technique has the potential to summarize a tremendous amount of research evidence, which can help making evidence-based decisions in policy, practice, and theory. This paper examines the single-case meta-analyses within the Education and Psychology fields. The amount of methodological studies related to the meta-analysis of Single-Case Experimental Designs (SCEDs) is increasing rapidly, especially in these fields. This underscores the necessity of a succinct summary to help methodologists identify areas for further development in Education and Psychology research. It also aids applied researchers and research synthesists in discerning when to use meta-analytic techniques for SCED studies based on criteria such as bias, mean squared error, 95% confidence intervals, Type I error rates, and statistical power. Based on the summary of empirical evidence from 18 reports identified through a systematic search procedure, information related to meta-analytic techniques, data generation and analysis models, design conditions, statistical properties, conditions under which the meta-analytic technique is appropriate, and the study purpose(s) were extracted. The results indicate that three-level hierarchical linear modeling is the most empirically validated SCED meta-analytic technique, and parameter bias is the most prominent statistical property investigated. A large number of primary studies (more than 30) and at least 20 measurement occasions per participant are recommended for usage of SCED meta-analysis in Education and Psychology fields.

Multifaceted roles of LhWRKY44 in promoting anthocyanin accumulation in Asiatic hybrid lilies (Lilium spp.).

The Asiatic hybrid lily (Lilium spp.) is a horticultural crop with high commercial value and diverse anthocyanin pigmentation patterns. However, the regulatory mechanism underlying lily flower color has been largely unexplored. Here, we identified a WRKY transcription factor from lily tepals, LhWRKY44, whose expression was closely associated with anthocyanin accumulation. Functional verification indicated that LhWRKY44 positively regulated anthocyanin accumulation. LhWRKY44 physically interacted with LhMYBSPLATTER and directly bound to the LhMYBSPLATTER promoter, which enhanced the effect of the LhMYBSPLATTER-LhbHLH2 MBW complex activator on anthocyanin accumulation. Moreover, EMSA and dual-luciferase assays revealed that LhWRKY44 activated and bound to the promoters of gene LhF3H and the intracellular anthocyanin-related glutathione S-transferase gene LhGST. Interestingly, our further results showed that LhWRKY44 participated in light and drought-induced anthocyanin accumulation, and improved the drought tolerance in lily via activating stress-related genes. These results generated a multifaceted regulatory mechanism for the LhWRKY44-meditaed enhancement by the environmental signal pathway of anthocyanin accumulation and expanded our understanding of the WRKY-mediated transcriptional regulatory hierarchy modulating anthocyanin accumulation in Asiatic hybrid lilies.

Assessing the needs of informal caregivers of patients with chronic non-communicable diseases: A systematic review of self-assessment tools.

AIM: To synthesize self-administrated needs assessment tools of informal caregivers for patients with chronic non-communicable diseases (CNCDs), evaluate the quality of psychometric properties and identify main needs assessment themes. DESIGN: Systematic review. METHODS: Eight electronic databases both in English and Chinese were searched for. The psychometric properties of tools were evaluated according to the quality criteria for good psychometric properties developed by Terwee et al. Both the content analysis and thematic extraction methods were used. Needs assessment themes were categorized based on the 7-level Maslow's Hierarchy of Needs Theory. RESULTS: A total of 17 tools were synthesized. Thirteen of them targeted informal caregivers of patients with cancer. The psychometric properties evaluated for most of these tools were content validity, internal consistency and construct validity. A total of 27 needs themes were identified and matched to six levels based on the 7-level Maslow's Hierarchy of Needs theory, besides the aesthetic needs level. NO PATIENT OR PUBLIC CONTRIBUTION: No primary data are being collected.

MYL3 protects chondrocytes from senescence by inhibiting clathrin-mediated endocytosis and activating of Notch signaling.

As the unique cell type in articular cartilage, chondrocyte senescence is a crucial cellular event contributing to osteoarthritis development. Here we show that clathrin-mediated endocytosis and activation of Notch signaling promotes chondrocyte senescence and osteoarthritis development, which is negatively regulated by myosin light chain 3. Myosin light chain 3 (MYL3) protein levels decline sharply in senescent chondrocytes of cartilages from model mice and osteoarthritis (OA) patients. Conditional deletion of Myl3 in chondrocytes significantly promoted, whereas intra-articular injection of adeno-associated virus overexpressing MYL3 delayed, OA progression in male mice. MYL3 deficiency led to enhanced clathrin-mediated endocytosis by promoting the interaction between myosin VI and clathrin, further inducing the internalization of Notch and resulting in activation of Notch signaling in chondrocytes. Pharmacologic blockade of clathrin-mediated endocytosis-Notch signaling prevented MYL3 loss-induced chondrocyte senescence and alleviated OA progression in male mice. Our results establish a previously unknown mechanism essential for cellular senescence and provide a potential therapeutic direction for OA.