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The Echiura worm Urechis unicinctus refers to a common benthic invertebrate found in the intertidal zone of Huanghai as well as Bohai Bay. U. unicinctus is known to contain various physiologically active substances, making it highly valuable in terms of its edibility, medicinal properties, and economic potential. Nonetheless, the limited study on the immune system of U. unicinctus poses difficulties for its aquaculture and artificial reproduction. Marine invertebrates, including shellfish and U. unicinctus, are thought to primarily depend on their innate immune system for disease protection, owing to the severalinnate immune molecules they possess. Herein, we employed PacBio single-molecule real-time (SMRT) sequencing technology to perform the full-length transcriptome analysis of U. unicinctus individuals under five different conditions (room temperature (RT), low temperature (LT), high temperature (HT), without water (DRY), ultraviolet irradiation (UV)). Concequently, we identified 59,371 unigenes that had a 2,779 bp average length, 2,613 long non-coding RNAs (lncRNAs), 59,190 coding sequences (CDSs), 35,166 simple sequence repeats (SSRs), and 1,733 transcription factors (TFs), successfully annotating 90.58 % (53,778) of the unigenes. Subsequently, key factors associated with immune-related processes, such as non-self-recognition, cellular immune defenses, and humoral immune defenses, were searched. Our study also identified pattern recognition receptors (PRRs) that included 17 peptidoglycan recognition proteins (PGRPs), 13 Gram-negative binding proteins (GNBPs), 18 scavenger receptors (SRs), 74 toll-like receptors (TLRs), and 89 C-type lectins (CLTs). Altogether, the high-quality transcriptome obtained data will offer valuable insights for further investigations into U. unicinctus innate immune response, laying the foundation for subsequent molecular biology studies and aquaculture., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Glass and crystal are inherently different material states in terms of their structural and physical features; consequently, the direct quantitative connection between crystal and glass is lacking. Herein, we first show that the liquid fragility m, which is featured by the negative departure degree of viscosity with the temperature at the glass transition temperature (Tg), has a direct exponential correlation with the ratio of the average longest metal-oxygen and the average phosphorus, silicon, or boron-oxygen bond lengths of the crystal in various oxides including phosphates, silicates, and borates. Such a result can be rationalized by the fact that the fragility m in these glass-formers is associated with the total network rigidity determined by the weakest bond due to the "bucket effect" and the bond pair inheritance of glass from that of the crystal. Our work connects direct features between glass and crystal with identical composition, providing a new viewpoint bridging glass and crystal., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

The efficacy of β-agonists in asthma is severely limited by β-adrenoceptor desensitization which results in poorly managed symptoms and refractory bronchoconstriction. Thus, there is a need to identify novel therapeutic pathways and to clarify the relationship between novel therapeutics and functional β-adrenoceptor responsiveness. We have previously demonstrated that acute antagonism of the calcium activated chloride channel, transmembrane member 16A (TMEM16A), relaxes airway smooth muscle (ASM). We sought to determine the efficacy and role of TMEM16A antagonism in the context of desensitization β - adrenoceptor responsiveness. For these studies, we exposed murine tracheal rings on wire myography and precision cut lung slices to contractile mediators in the presence or absence of TMEM16A antagonists and β-agonists with or without prior β-adrenoceptor desensitization. Contractile studies were also performed with human tracheal and bronchial ASM. Finally, the ability of TMEM16A antagonism to prevent desensitization of β 2 -adrenoceptor-induced cyclic AMP synthesis was measured in human ASM cells. From these studies we demonstrate that acute TMEM16A antagonism is effective in relaxing β-agonist desensitized ASM in central and peripheral murine ASM and human ASM. Furthermore, we demonstrate that chronic pretreatment with TMEM16A antagonists prevents functional desensitization of β-agonist responsiveness in mouse and human upper airways and prevents desensitization of β-agonist-mediated cyclic AMP production in human ASM cells. Taken together, the present study demonstrates a favorable therapeutic profile of TMEM16A antagonism for airway smooth muscle relaxation despite functional desensitization of β-agonist responsiveness which may be a novel therapeutic approach in the face of β-adrenoceptor tachyphylaxis.

Photodynamic therapy (PDT), a minimally invasive and effective local treatment, heavily depends on photosensitizer (PS) performance and oxygen availability. Despite the use of PS-based metal-organic frameworks (MOFs) to address the solubility and aggregation issues of PSs, the inherent hypoxic intolerance of mainstream Type II PDT remains challenging. Herein, we report an electron transfer strategy for the fabrication of hypoxia-tolerant Type I MOFs by encapsulating thymoquinone (TQ) into existing Type II MOFs. With TQ serving as an effective electron transfer mediator, it facilitates the electron transfer process from the MOF ligand PS to oxygen, establishing the Type I pathway and attenuating the original Type II pathway. Four representative porphyrin-based MOFs are synthesized to demonstrate the proposed strategy. Our findings reveal that TQ@MOF-1 nanoparticles (NPs) exhibit enhanced anticancer activity under hypoxic conditions and superior in vivo antitumor efficacy compared to parent MOF-1 NPs. This work offers an effective and universal strategy to modulate ROS generation in PS-based MOFs, endowing hypoxic tolerance with improved PDT performance against solid tumors., (© 2024 Wiley‐VCH GmbH.)

Nonketotic hyperglycemia-induced hemichorea is a rare condition of type 2 diabetes. It is characterized by hyperglycemia with the symptom traced to the basal ganglion like hemichorea or hemiballism, with the hyperintensity within basal ganglion presented in computed tomography (CT) or hyper signal in T1-weighted magnetic resonance image (MRI). It was also confirmed with a relatively better prognosis in that the symptoms of these patients could be relieved after the alleviation of hyperglycemia. However, the exact pathophysiology or mechanism of this condition currently was unclear. Besides, the duration of improvement in tomography as far was varied. In the present study, we reported an elderly female patient who tested with nonketotic hyperglycemia (random blood glucose of fingertips was 19 mmol/L or 342 mg/dL, blood ketone was 0.1 mmol/L) with the symptoms of dysphoria and mild chorea of left low limb, the MRI and CT showed contralateral striatopathy. Her condition achieved alleviation after the normalization of blood glucose. We subsequently rechecked her MRI in arterial spin labeling sequence which showed the hypoperfusion in the right basal ganglion rather than the opposite. Therefore, we suppose the hyperglycemia could induce temporary hypoperfusion in the basal ganglion associated with motor dysfunction which is manifested by hemichorea or hemiballism.

Circularly polarized luminescent (CPL) materials have garnered considerable interest for a variety of advanced optical applications including 3D imaging, data encryption, and asymmetric catalysis. However, the development of high-performance CPL has been hindered by the absence of simple synthetic methods for chiral luminescent emitters that exhibit both high quantum yields and dissymmetry factors. In this study, we present an innovative approach for the synthesis of macro-chiral liquid crystal quantum dots (Ch-QDs/LC) and their CPL performance enhancement through doping with 4-cyano-4'-pentylbiphenyl (5CB), thus yielding a CPL-emitting generator (CEG). The Ch-QDs/LCs were synthesized, and their surfaces functionalized with a chiral mesogenic ligand, specifically cholesteryl benzoate, anchored via a lipoic acid linker. Under the regulation of chiral 2S-Zn 2+ coordination complexes, the chiral LC encapsulation process promotes coordinated ligand substitution, resulting in an exceptional quantum yield of 56.3%. This is accompanied by high absorption dissymmetry factor ( g abs ) and luminescence dissymmetry factor ( g lum ) values ranging from 10 -3 to 10 -2 , surpassing most reported dissymmetry factors by at least an order of magnitude. The modular Ch-QDs/LCs demonstrate the ability to transfer chirality to the surrounding medium efficiently and manifest macro-chiral characteristics within a nematic LC matrix. Utilizing Ch-QDs/LC as an effective CPL emitter within achiral 5CB matrices enabled the system to achieve a maximum g lum value of 0.35. The resultant CEG device acted as a direct CPL source, initiating enantioselective photopolymerization.

Cane molasses, a sugar-rich agro-industrial byproduct, was used to enhance the production of ε-poly-l-lysine (ε-PL) in Streptomyces albulus PD-1 as a cost-effective carbon source. The sucrose metabolism pathway was engineered by heterologously expressing sucrose-6-phosphate hydrolase from Escherichia coli W. The optimization of various promoters identified the SP44 promoter, increasing the total sugar utilization rate by 2.76-fold compared with the ermEp* promoter. Additionally, adaptive laboratory evolution improved the total sugar utilization rate. The evolved strain achieved an ε-PL titer of 2.65 ± 0.15 g/L in flask experiments, increasing the ε-PL titer by 7.16-fold compared with the unevolved strain. Comparative transcriptomic analyses revealed that the enhanced tolerance of the evolved strain to high concentrations of cane molasses was primarily due to modifications in the sucrose metabolism pathways, microbial metabolism in heavy metals and phenols, and the amino acids transport and metabolic pathways. These changes enabled more efficient ε-PL production. During fed-batch fermentation in a 5-L fermentor using a concentration of 50 g/L cane molasses, the ε-PL titer reached 36.88 ± 0.62 g/L, and dry cell weight was 41.1 ± 1.0 g/L. This study illustrates that cane molasses is an economical carbon source for producing ε-PL on an industrial scale.

Background: Cervical lymph node metastasis (CLNM) is the most common form of thyroid cancer metastasis. Accurate preoperative CLNM diagnosis is of more importance in patients with papillary thyroid cancer (PTC). However, there is currently no unified methods to objectively predict CLNM risk from ultrasonography in PTC patients.This study aimed to develop a deep learning (DL) model to help clinicians more accurately determine the existence of CLNM risk in patients with PTC and then assist them with treatment decisions., Methods: Ultrasound dynamic videos of 388 patients with 717 thyroid nodules were retrospectively collected from Zhejiang Cancer Hospital between January 2020 and June 2022. Five deep learning (DL) models were investigated to examine its efficacy for predicting CLNM risks and their performances were also compared with those predicted using two-dimensional ultrasound static images., Results: In the testing dataset (n = 78), the DenseNet121 model trained on ultrasound dynamic videos outperformed the other four DL models as well as the DL model trained using the two-dimensional (2D) static images across all metrics. Specifically, using DenseNet121, the comparison between the 3D model and 2D model for all metrics are shown as below: AUROC: 0.903 versus 0.828, sensitivity: 0.877 versus 0.871, specificity: 0.865 versus 0.659., Conclusions: This study demonstrated that the DenseNet121 model has the greatest potential in distinguishing CLNM from non-CLNM in patients with PTC. Dynamic videos also offered more information about the disease states which have proven to be more efficient and robust in identifying CLNM compared to statis images., Competing Interests: Compliance with ethical standards Conflict of interest The authors declare no competing interests. Ethics approval and consent to participate This retrospective study’s protocol was approved by the Independent Ethics Committee of Zhejiang Cancer Hospital (NO: IRB-2020-287), and written informed consent from the patient was waived by the ethics committee of the Independent Ethics Committee of Zhejiang Cancer Hospital. Patient records were anonymised and deidentified before analysis. We confirm that all methods were performed in accordance with the relevant guidelines and regulations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The committed step for de novo fatty acid (FA) synthesis is the ATP-dependent carboxylation of acetyl-coenzyme A catalysed by acetyl-CoA carboxylase (ACCase). In most plants, ACCase is a multi-subunit complex orthologous to prokaryotes. However, unlike prokaryotes, the plant and algal orthologues are comprised both catalytic and additional dedicated regulatory subunits. Novel regulatory subunits, biotin lipoyl attachment domain-containing proteins (BADC) and carboxyltransferase interactors (CTI) (both three-gene families in Arabidopsis ) represent new effectors specific to plants and certain algal species. The evolutionary history of these genes in autotrophic eukaryotes remains elusive, making it an ongoing area of research. Analyses of potential protein-protein and co-occurrence interactions, informed by gene network patterns using the STRING database, in Arabidopsis thaliana and Chlamydomonas reinhardtii unveil intricate gene associations with ACCase, suggesting a complex interplay between FA synthesis and other cellular processes. Among both species, a higher number of co-expressed genes was identified in Arabidopsis , indicating a wider potential regulatory network of ACCase in plants. This review investigates the extent to which these genes arose in autotrophic eukaryotes and provides insights into their evolutionary trajectory. This article is part of the theme issue 'The evolution of plant metabolism'.

Background: Intranasal transplantation of ANGE-S003 human neural stem cells showed therapeutic effects and were safe in preclinical models of Parkinson's disease (PD). We investigated the safety and tolerability of this treatment in patients with PD and whether these effects would be apparent in a clinical trial., Methods: This was a 12-month, single-centre, open-label, dose-escalation phase 1 study of 18 patients with advanced PD assigned to four-time intranasal transplantation of 1 of 3 doses: 1.5 million, 5 million or 15 million of ANGE-S003 human neural stem cells to evaluate their safety and efficacy., Results: 7 patients experienced a total of 14 adverse events in the 12 months of follow-up after treatment. There were no serious adverse events related to ANGE-S003. Safety testing disclosed no safety concerns. Brain MRI revealed no mass formation. In 16 patients who had 12-month Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) data, significant improvement of MDS-UPDRS total score was observed at all time points (p<0.001), starting with month 3 and sustained till month 12. The most substantial improvement was seen at month 6 with a mean reduction of 19.9 points (95% CI, 9.6 to 30.3; p<0.001). There was no association between improvement in clinical outcome measures and cell dose levels., Conclusions: Treatment with ANGE-S003 is feasible, generally safe and well tolerated, associated with functional improvement in clinical outcomes with peak efficacy achieved at month 6. Intranasal transplantation of neural stem cells represents a new avenue for the treatment of PD, and a larger, longer-term, randomised, controlled phase 2 trial is warranted for further investigation., Competing Interests: Competing interests: XS and XZ are employees of Angecon Biotechnology Co, Ltd. The other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Rumen microbiotas are known to influence the fat deposition (FD) in sheep, but controversy over causality remains unresolved. Here, we performed microbiome-wide association studies (MWAS), microbiome genome-wide association analysis (mbGWAS) and bidirectional mendelian randomization (MR) analyses on 1,150 sheep with genotype data from whole-genome resequencing, 16S rRNA sequencing and multilevel FD-traits data. We quantified the proportion of individual variation in FD-traits explained by host genetics, rumen microbiota, and their interaction effects. We identified 32 rumen microbiota biomarkers including Bifidobacterium that were associated with FD-traits (P adj <0.05). Further, utilizing five MR methods, we identified eight causal associations between marker genera and FD-traits (P adj <0.05), including Butyrivibrio, Olsenella, p-2534-18B5 gut group, Prevotellaceae UCG-003, and Pseudobutyrivibrio causing forward causal effects on FD, and changes in Flexilinea and Suttonella induced by FD. To our knowledge, this is the inaugural attempt to employ MR in sheep to investigate the causal relationships between gastrointestinal microbiota and complex phenotypes, underscoring the potential for developing interventions related to adipose deposition in sheep from the perspective of the rumen microbiome., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval All animal experiments and procedures were conducted under the approval and guidance of the Animal Ethics Committee of Lanzhou University (Nos.: 2020-01 and 2021-02)., (© 2024. The Author(s).)

Objectives: Human leukocyte antigen G (HLA-G) plays a crucial role in pregnancy. Pregnancy loss (PL) is caused by a variety of causes, such as fetal chromosomal abnormalities, maternal hypertension and diabetes, immune causes, spontaneous immune diseases, infections, unknown causes, etc. This study reports on the association of fetal HLA-G 3'UTR polymorphisms and diplotypes with chromosomally abnormal fetuses (CAF) or unexplained pregnancy loss (UPL)., Methods: A total of 552 specimens were collected and grouped by next-generation sequencing technology (NGS) and fetal survival: UPL (112 cases), CAF (170 cases) and control (258 cases). The polymorphisms of HLA-G 3'UTR in all samples were detected by Sanger sequencing. The genotypes, haplotypes and diplotypes of HLA-G 3'UTR were analyzed. The classification and regression tree (CART) analysis was used to evaluate the role of HLA-G diplotypes in predicting fetal outcomes. The correlations between CAF or UPL and maternal age, paternal age, times of miscarrage, times of delivery were analyzed by logistic regression., Results: The frequencies of HLA-G + 2960del/del and + 3035CC genotypes were remarkablly increased in CAF than those in control group. The frequencies of HLA-G + 2960ins/del, + 3010CC, + 3035TC, + 3142GG, + 3187AA in CAF were significantly lower than those in normal fetuses. Through genetic models and logistic regression analysis, the dominant model of HLA-G 3'UTR genotypes [such as + 2960 (OR = 1.27, 95% CI = 1.05-1.54, p = 0.016), + 3010 (OR = 0.78, 95% CI = 0.63-0.97, p = 0.026), + 3035 (OR = 1.22, 95% CI = 1.00-1.49, p = 0.047), + 3142 (OR = 0.76, 95% CI = 0.62-0.95, p = 0.014) and + 3187 (OR = 0.80, 95% CI = 0.65-0.99, p = 0.041)] were dramatically associated with CAF. However, the frequencies of HLA-G + 3010GC, + 3142GC and + 3187AG in fetuses with UPL were memorably decreased than those in normal fetuses. No significant difference was found in the frequencies of HLA-G haplotypes in all groups. However, the frequency of UTR-1 positive specimens in CAF was significantly higher than that in UPL and control group. At the same time, the frequency of UTR-1/UTR-3 diplotypes in CAF was observably higher than that in UPL and control group, while the UTR-1/UTR-7 frequency in UPL was signally lower than that in control group. Multivariate logistic regression analysis indicated that positive HLA-G UTR-1 (OR = 1.8, 95% CI = 1.16-2.81, p = 0.009), times of abortion (OR = 1.23, 95% CI = 1.02-1.50, p = 0.035), and times of delivery (OR = 0.31, 95% CI = 0.20-0.48, p < 0.001) were correlated with CAF., Conclusions: This study suggests that HLA-G 3'UTR polymorphisms and diplotypes play an important role in the process of successful pregnancy of the embryos with abnormal chromosomes after fertilization. At the same time, Different alleles or diplotypes also affect the development of embryos with UPL., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Medical Ethics Review Committee of Taizhou Hospital (approval #K20231035), and written informed consent from all study participants was obtained before enrolment. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Urban greening (UG) affects local climate by altering surface energy balance, while long-term UG cooling potential, patterns, and contribution to curbing urban warming remain unclear. Here, we designed an novel statistical model to evaluate the cooling potential of UG (CPUG) and created the first CPUG map for China. By exploring the trends in observed and simulated urban surface temperatures (UST), we quantified the CPUG of 0.20 K over the past two decades, which slowed down the warming trend by 14.17% in Chinese cities. We found that the CPUG varied significantly between the urban core and sprawl areas. Specifically, the CPUG in the urban core was approximately 1.01 K, and it contributed to curbing urban warming by 56.08%, which was more than 7.2 times higher than in the sprawl areas, where the CPUG was only 0.14 K and contributed to curbing urban warming by 9.93%. We further revealed that urbanization and major ecological restoration projects are the key factors influencing CPUG, emphasizing the need for anthropogenic vegetation management to curb urban warming. The proposed model in this study provides a powerful tool for quantitatively assessing the impact of long-term UG trends on urban warming. The results of the study are an important reference for building climate-adaptive cities.

Hip fractures significantly affect patients' health and quality of life. Despite therapeutic treatments, many patients continue to experience poor prognoses that include recurrent fractures and mortality, especially the older ones. Therefore, understanding important factors associated with post-fracture prognoses is critical. This study focuses on patients' multimorbidity trajectories and examines how the trajectory's time span, number of coexisting chronic diseases, and sequential disease patterns relate to distinct prognostic outcomes. From the National Health Insurance Research Database in Taiwan, we obtain a sample of 128,822 patients who suffered an initial hip fracture between 1996 and 2011. We use this sample to analyze the relationships between multimorbidity trajectories and prognostic outcomes after an initial hip fracture. The results reveal that a patient's multimorbidity trajectory's time span and number of chronic diseases significantly associate with his or her post-fracture prognosis. In addition, essential sequential patterns of chronic diseases relate to post-fracture prognoses too. We then leverage the discovered relationships to develop a cross-attention neural network method for estimating patients' post-fracture prognoses and demonstrate its predictive utilities relative to several prevalent machine leaning methods. This study underscores the importance of leveraging the time span, number of chronic diseases, and sequential disease patterns in patients' multimorbidity trajectory profile to estimate their prognoses within three years of an initial hip fracture, which can support physicians' clinical decisions and patient management., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Endosulfan, recognized as an endocrine disruptor, has emerged as an important risk factor for human breast cancer. The chemokine ligand 5 (CCL5) and its receptor CCR5 constitute a biological axis, that is implicated in tumorigenesis and cancer progression. However, the role of the CCL5/CCR5 axis in breast cancer when exposure to endosulfan remains unclear. The present study aimed to determine the significance of the CCL5/CCR5 axis in the carcinogenic effects of endosulfan in human breast cancer MCF-7 cells. The results showed that endosulfan significantly promoted cell proliferation, increased the rate of colony formation, and enhanced cell migration ability in a dose-dependent manner by activating the PI3K/AKT signaling pathway, which were rescued by the specific inhibitor (LY-294002) for PI3K/AKT signaling pathway. We utilized Cytoscape software to construct protein-protein interaction (PPI) network when exposure to endosulfan, and identified 47 highly connected genes in the network diagram centered on CCL5. Endosulfan significantly increased the secretion of CCL5 and the expression levels of CCL5/CCR5, which were reversed by CCR5 inhibitor (HY-13004). HY-13004 significantly counteracted the effects of endosulfan on colony formation, cell migration and the activation of PI3K/AKT signaling pathway. Endosulfan markedly altered the expression levels of epithelial-mesenchymal transition (EMT) biomarkers and enhanced transwell migration and invasion capabilities of MCF-7 cells, which were inhibited by HY-13004, similar to the effects observed with LY-294002. Collectively, our findings suggest that endosulfan activates the PI3K/AKT signaling pathway to promote cell growth, and induces EMT, thereby enhancing cell migration and invasion via the CCL5/CCR5 axis in MCF-7 cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Arketamine, the (R)-enantiomer of ketamine, exhibits both therapeutic and sustained prophylactic effects in an inflammation-driven model of depression, although the precise mechanisms remain elusive. Given the involvement of γδ T cells in inflammatory processes, this study explored their role in the effects of arketamine. To assess therapeutic outcomes, mice received lipopolysaccharide (LPS:1.0 mg/kg), followed by either arketamine (10 mg/kg) or saline. For prophylactic assessment, arketamine or saline was administered six days prior to LPS exposure. A single dose of LPS (1.0 mg/kg) reduced the proportion of γδ T cells in the spleen but did not affect their levels in the blood, prefrontal cortex, or small intestine. Arketamine mitigated LPS-induced splenomegaly, counteracted the elevation of plasma interleukin-6 levels and the reduction in the proportion of splenic γδ T cells, and alleviated depression-like behavior as assessed by the forced swimming test. Notably, negative correlations were observed between the proportion of splenic γδ T cells and indicators of inflammation and depression. Furthermore, pretreatment with a γδ TCR antibody significantly countered the therapeutic and prophylactic effects of arketamine on LPS-induced changes. These findings highlight a novel role for splenic γδ T cells in inflammation-associated depression and suggest the potential of arketamine as a treatment option. Consequently, γδ T cells may represent a novel therapeutic target for inflammation-related depression. Further studies on the role of γδ T cells in depressed patients with inflammation are warranted., Competing Interests: Declaration of competing interest Dr. Hashimoto is one of the editorial board members of this journal. Dr. Hashimoto is the inventor of filed patent applications on “The use of R-ketamine in the treatment of psychiatric diseases”, “(S)-norketamine and salt thereof as pharmaceutical”, “R-ketamine and derivative thereof as prophylactic or therapeutic agent for neurodegeneration disease or recognition function disorder”, “Preventive or therapeutic agent and pharmaceutical composition for inflammatory diseases or bone diseases”, and “R-ketamine and its derivatives as a preventive or therapeutic agent for a neurodevelopmental disorder” by the Chiba University. Dr. Hashimoto has also received speakers' honoraria, consultant fee, or research support from Otsuka. Other authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Microcystins (MCs) pollution is a worldwide environmental issue concerning about human health. Microcystin-leucine-arginine (MC-LR), the most common type of MCs produced by cyanobacteria, could enter the brain and bring about damage to the nervous system. Up to date, it is not clear about the mechanism of MC-LR-induced neurotoxicity. Amyloid-β (Aβ) deposits are hallmark of Alzheimer's disease (AD). In this study, we revealed that MC-LR exposure at environment-related doses (1, 7.5, 15 μg/L) could promote Aβ accumulation in mouse brain. Mechanically, we firstly found that Aβ accumulation is closely associated with abnormal Aβ degradation due to autophagy flux blockade and lysosome dysfunctions in neurons after MC-LR exposure. Moreover, an adverse outcome pathway (AOP) framework oriented to neurotoxicity of MC-LR was conducted in this study. MC-LR inhibited the activity of protein phosphatase 2A (PP2A) in neurons, which is regarded as a molecular initiating event (MIE). In addition, the abnormalities in autophagy were observed after MC-LR exposure. The hindered autophagosome-lysosome fusion and disrupted lysosomal function were key events (KEs) after MC-LR exposure, which contributed to proteostasis dysregulation, ultimately leading to Aβ abnormal degradation and learning deficits as adverse outcomes (AO) of neurotoxicity. This study provided novel information about MC-LR neurotoxicity and new insights into understanding the mechanisms underlying the environmental chemicals-induced neurodegeneration diseases, which has deep implications for public health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Alzheimer's disease (AD) is a common elderly disorder characterized by cognitive decline. Endoplasmic reticulum (ER) stress has been implicated in various neurodegenerative diseases, including AD. Stem cell factor (SCF) performs its biological functions by binding to and activating receptor tyrosine kinase c-Kit. We aimed to investigate the effects of SCF/c-Kit and JAK2/STAT3 on ER stress and apoptosis in AD., Methods: The study employed L-glutamic acid (L-Glu)-treated HT22 cells as sporadic AD cell model and APP/PS1 mice as an animal model of familiar AD. SCF, c-Kit inhibitor ISCK03 or JAK2/STAT3 inhibitor WP1066 was treated to verify the effects of SCF/c-Kit and JAK2/STAT3 on ER stress and apoptosis of L-Glu-exposed HT22 cells. Cell viability was assessed by MTT. BrdU detected cell proliferation. Flow cytometry measured cell apoptosis. The expression levels of ER stress markers GRP78, PERK, CHOP, and apoptosis protein caspase3 were determined by western blot. The effect on the mRNA of ER stress markers GRP78, PERK, CHOP and apoptotic caspase3 were quantified by RT-qPCR in primary cultured hippocampal neurons from APP/PS1 transgenic mice., Results: Administration of SCF significantly augmented the activity and proliferation of hippocampal neuronal cells, protecting cells against L-Glu induced ER stress-associated apoptosis. Moreover, the addition of ISCK03 (c-Kit inhibitor) or WP1066 (JAK2/STAT3 inhibitor) reversed SCF effects on ER stress and apoptosis in vitro., Conclusion: We found that SCF inhibits L-Glu-induced ER stress-associated apoptosis via JAK2/STAT3 axis in HT22 hippocampal neuronal cells, as well as in primary hippocampal neurons from APP/PS1 mice, which provides valuable insights into the molecular mechanisms underlying the pathogenesis of AD and explores novel therapeutic targets for both sporadic and familial AD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Long-term human spaceflight can lead to cardiovascular deconditioning, but little is known about how weightlessness affects microcirculation. In this study, we examined how the retinal microvessels and cerebrovascular regulation of 19 healthy male participants responded to long-term head-down bedrest (HDBR), an earth-based analog for weightlessness. In addition, we examined whether an anti-inflammatory/antioxidant cocktail could prevent the vascular changes caused by HDBR. In all study participants, we found a decrease in retinal arteriolar diameter by HDBR day 8 and an increase in retinal venular diameter by HDBR day 16. Concurrently, blood pressure at the level of the middle cerebral artery and the cerebrovascular resistance index were higher during HDBR, while cerebral blood flow velocity was lower. None of these changes were reversed in participants receiving the anti-inflammatory/antioxidant cocktail, indicating that this cocktail was insufficient to restore the microvascular and cerebral blood flow changes induced by HDBR., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Despite widespread deployment and investigation of ultrafiltration (UF) for secondary effluent purification, the challenge of membrane fouling due to effluent organic matter (EfOM) remains formidable. This study introduced a novel pretreatment method utilizing Co nanoparticles-encapsulated carbon nanotubes activated peroxymonosulfate (Co@CNT/PMS) to degrade EfOM and mitigate membrane fouling. Characterization of Co@CNT revealed the efficient encapsulation of Co nanoparticles within nanotubes, which notably enhanced the catalytic degradation of bisphenol A and typical organics. The tube-encapsulated structure increased the concentration of reactive species within the confined nanoscopic space, thereby improving the probability of collisions with pollutants and promoting their degradation. The Co@CNT/PMS pretreatment led to substantial reductions in aromatic compounds, fluorescent components, and both high and middle molecular weight substances. These changes proved crucial in diminishing the fouling potential in subsequent UF processes, where reversible and irreversible fouling resistances decreased by 97.1 % and 72.8 %, respectively. The transition volume from pore blocking to cake filtration markedly increased, prolonging the formation of a dense fouling layer. Surface properties analysis indicated a significant reduction of pollutants on membrane surfaces after the Co@CNT/PMS pretreatment. This study underscored the efficacy of confinement-based advanced oxidization pretreatment in enhancing UF performance, presenting a viable resolution to membrane fouling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

As a foodborne pathogen capable of causing severe illnesses, early detection of Escherichia coli O157:H7 (E. coli O157:H7) is crucial for ensuring food safety. While Förster resonance energy transfer (FRET) is an efficient and precise detection technique, there remains a need for amplification strategies to detect low concentrations of E. coli O157:H7. In this study, we presented a phage (M13)-induced "one to many" FRET platform for sensitively detecting E. coli O157:H7. The aptamers, which specifically recognize E. coli O157:H7 were attached to magnetic beads as capture probes for separating E. coli O157:H7 from food samples. The peptide O157S, which specifically targets E. coli O157:H7, and streptavidin binding peptide (SBP), which binds to streptavidin (SA), were displayed on the P3 and P8 proteins of M13, respectively, to construct the O157S-M13K07-SBP phage as a detection probe for signal output. Due to the precise distance (≈3.2 nm) between two neighboring N-terminus of P8 protein, the SA-labeled FRET donor and acceptor can be fixed at the Förster distance on the surface of O157S-M13K07-SBP via the binding of SA and SBP, inducing FRET. Moreover, the P8 protein, with ≈2700 copies, enabled multiple FRET (≈605) occurrences, amplifying FRET in each E. coli O157:H7 recognition event. The O157S-M13K07-SBP-based FRET sensor can detect E. coli O157:H7 at concentration as low as 6 CFU/mL and demonstrates excellent performance in terms of selectivity, detection time (≈3 h), accuracy, precision, practical application, and storage stability. In summary, we have developed a powerful tool for detecting various targets in food safety, environmental monitoring, and medical diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD) not only could cause abnormal lipid metabolism in the liver, but also could cause liver inflammation. Previous studies have shown that Polysaccharide of Atractylodes macrocephala Koidz (PAMK) could alleviate animal liver inflammatory damage and alleviate NAFLD in mice caused by high-fat diet(HFD), but regulation of liver inflammation caused by NAFLD has rarely been reported. In this study, an animal model of non-alcoholic fatty liver inflammation in the liver of mice was established to explore the protective effect of PAMK on the liver of mice. The results showed that PAMK could alleviate the abnormal increase of body weight and liver weight of mice caused by HFD, alleviate the abnormal liver structure of mice, reduce the level of oxidative stress and cytokine secretion in the liver of mice, and downregulate the mRNA expression of TLR4, MyD88, NF-κB and protein expression of P-IκB, P-NF-κB-P65, TLR4, MyD88, NF-κB in the liver. These results indicate that PAMK could alleviate hepatocyte fatty degeneration and damage, oxidative stress and inflammatory response of the liver caused by NAFLD in mice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The allure of substantial profits has perpetuated the illicit trade of counterfeit vintage labels for baijiu. While various approaches have been employed to intelligently ascertain the vintage of baijiu, many of them are both cost-intensive and time-consuming. This work pioneered the use of Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, coupled with chemometric analysis, offering a non-destructive and economically viable method for discriminating sauce-flavor baijiu across different aging periods (1-, 2-, and 3-year). In this research, principal component analysis (PCA) was first conducted to explore clustering trends among distinct vintage groups. Subsequently, the effect of spectral pre-processing on modeling performance was explored. For wavelength selection, four wavelength selection methods (ReliefF, random forest variable importance (RFVI), variable importance in projection (VIP), and Venn) were first used to identify the subset of candidate features that potentially best mapped the vintage labels. Immediately following this, to explore the possibility of further improving the identification capabilities of the model as well as to reduce the redundant data that may still be present, sequential backward selection (SBS) was utilized for secondary feature reduction within the subset of candidates. The amalgamation of these two techniques is termed a "hybrid wavelength selection strategy." Additionally, the dimensionality reduction effects of PCA and kernel principal component analysis (KPCA) were compared to demonstrate the robustness of the proposed method. Finally, classification models such as partial least squares discriminant analysis (PLS-DA), random forest (RF), and grasshopper optimization algorithm-based support vector machine (GOA-SVM) were developed. The results show that the spectral data need not be pre-processed, and the proposed hybrid wavelength selection strategy can further improve the identification ability of the model. Among the many models developed, ReliefF-SBS-GOA-SVM emerged as the most proficient classification model, yielding accuracy, sensitivity, and specificity rates of 94.44%, 95.23%, and 94.44%, respectively. This method not only holds promise for the discrimination of baijiu class attributes such as brand, origin, flavor, and vintage but also exhibits potential applicability in other non-targeted identification studies involving spectroscopy methodologies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Osteopontin (Opn) depletion can improve septic outcomes, but the underlying mechanism remains unknown. In this study, we demonstrated that nonhematopoietic but not hematopoietic Opn depletion improved septic outcomes. When compared with wild type mice, cohoused Opn-/- mice displayed enhanced production of antibacterial peptides (AMPs), decreased bacterial loads, and a distinct bacterial composition of gut microbiota. Fecal microbiota transplantation and OPN neutralization assay showed that Opn depletion could reduce bacterial loads and improve septic inflammation. By employing an intestinal organoid culture system, we proved that OPN neutralization in wild type organoids could inactivate AKT and decrease FOXO3a phosphorylation, resulting in enhanced AMP production, whereas OPN treatment in OPN-deficient organoids could activate AKT and increase FOXO3a phosphorylation, leading to reduced AMP production. Our findings identified OPN as a novel regulatory factor of AMP production to modulate bacterial loads and composition of gut microbiota, in turn affecting sepsis outcomes., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Ethnopharmacological Relevance: Alcoholic depression, a disorder of the central nervous system, is characterized by alcohol abuse, which causes blood-brain barrier disruption and oxidative damage in the brain. The rhizome of Rhodiola crenulate, from which Dazhu Hongjingtian Injection (DZHJTI) is derived, has been traditionally employed in ethnopharmacology to treat neurological disorders due to its neuroprotective, anti-inflammatory, and antioxidant properties. However, the exact mechanism by which DZHJTI alleviates alcoholic depression remains unclear., Aim of the Study: This study aimed to investigate the antidepressant effects of DZHJTI and its underlying mechanisms in a mouse model of alcohol-induced depression., Materials and Methods: A model of alcoholic depression was established using C57BL/6J mice, and the effects of DZHJTI on depression-like behaviors induced by alcohol exposure were assessed through behavioral experiments. Histopathological examination was conducted to observe nerve cell damage and microglial activation in the hippocampal region. Oxidative stress indices in the hippocampus, inflammatory factors, and serum levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) were measured using ELISA. Expression of proteins related to the Nrf2/HO-1/NLRP3 signaling pathway was determined by Western blot analysis., Results: DZHJTI attenuated depression-like behaviors, neuronal cell damage, oxidative stress levels, inflammatory responses, and microglial activation. It also restored levels of brain-derived neurotrophic factor, brain myelin basic protein, DA, and 5-HT in mice with chronic alcohol exposure. After DZHJTI treatment, the expressions of Nuclear Respiratory Factor 2 (Nrf2) and Heme Oxygenase-1 (HO-1) increased in the hippocampus, whereas the levels of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD, cleaved caspase-1, interleukin (IL)-1β, and IL-18 decreased., Conclusions: DZHJTI ameliorates alcohol-induced depressive symptoms in mice through its antioxidant and anti-inflammatory effects, involving mechanisms associated with the Nrf2/HO-1/NLRP3 signaling pathway. This study highlights the potential of DZHJTI as a therapeutic option for alcohol-related depression and suggests the scope for future research to further elucidate its mechanisms and broader clinical applications., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Macrophages are innate immune cells connected with the development of inflammation. Retinoic acid has previously been proved to have anti-inflammatory and anti-arthritic properties. However, the exact mechanism through which retinoic acid modulates arthritis remains unclear. This study aimed to investigate whether retinoic acid ameliorates rheumatoid arthritis by modulating macrophage polarization. This study used retinoic acid to treat mice with adjuvant arthritis and evaluated anti-inflammatory effects by arthritis score, thermal nociceptive sensitization test, histopathologic examination and immunofluorescence assays. In addition, its specific anti-arthritic mechanism was investigated by flow cytometry, cell transfection and inflammatory signaling pathway assays in RAW264.7 macrophages in vitro . Retinoic acid significantly relieved joint pain and attenuated inflammatory cell infiltration in mice. Furthermore, this treatment modulated peritoneal macrophage polarization, increased levels of arginase 1, as well as decreased inducible nitric oxide synthase expression. In vitro , we verified that retinoic acid promotes macrophage transition from the M1 to M2 type by upregulating mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression and inhibiting P38, JNK and ERK phosphorylation in lipopolysaccharide-stimulated RAW264.7 cells. Notably, the therapeutic effects of retinoic acid were inhibited by MKP-1 knockdown. Retinoic acid exerts a significant therapeutic effect on adjuvant arthritis in mice by regulating macrophage polarization through the MKP-1/MAPK pathway, and play an important role in the treatment of rheumatic diseases.

Background: CircRNAs have been demonstrated to play a crucial role in regulating the growth and progression of various cancers, including hepatocellular carcinoma (HCC). Nevertheless, the circRNA's expression pattern and function in HCC need more investigation., Methods: Bioinformatics techniques were used to identify differentially expressed circRNAs in HCC. CircASH2L expression in HCC tissues was assessed through qRT-PCR and ISH analysis. To assess circASH2L's impact on HCC progression, a variety of experiments were carried out both in vitro and in vivo, such as CCK8, colony formation, EdU assay, flow cytometry, transwell assay, and xenograft mouse model. Various experimental techniques including qRT-PCR, dual luciferase reporter assay, FISH, RNA pull-down, and RIP experiments were utilized to evaluate the relationship between circASH2L, miR-525-3p, and MTUS2. Additionally, experiments were conducted to explore the impact of m 6 A modification on circASH2L expression, including RNA stability assay, m 6 A RNA immunoprecipitation assay (MeRIP), and Co-IP experiments., Results: We found that circASH2L was downregulated in HCC tissues and the downregulation of circASH2L was significantly correlated with malignant characteristics as well as poor overall survival of patients with HCC. CircASH2L was found to inhibit cells growth, migration and invasion as well as tumorigenesis and metastasis in vivo. Mechanistically, we established that circASH2L directly interacted with miR-525-3p to enhance MTUS2 expression, subsequently leading to tumor suppression. Moreover, the influence of circASH2L on tumor suppression was attenuated by increasing miR-525-3p levels, and MTUS2 was recognized as an essential intermediary in circASH2L-induced tumor suppression. Additionally, N 6- methyladenosine (m6A) modification was identified in circASH2L. Our data suggested that METTL3 was responsible for mediating m 6 A methylation of circASH2L, ultimately regulating circASH2L expression through the promotion of its degradation. These findings collectively highlight the role of circASH2L as a tumor suppressor through a unique circASH2L/miR-525-3p/MTUS2 axis, shedding light on the significance of m 6 A modification in regulating circASH2L function., Conclusion: The work emphasizes circASH2L as a promising therapeutic target for treating HCC, offering new insights into the role of circRNAs in HCC development., Competing Interests: Declarations Ethics approval and consent to participate The procedure of human sample collection was approved by the Institutional Review Board of Tongji Medical College of Huazhong University of Science and Technology on 16 November 2021 (NO. TJ-IRB20211163) and all procedures were meet the criteria of the Declaration of Helsinki. Written informed consent for specimens was obtained from all patients. All of the animal experiments met the National Institutes of Health guidelines and were approved by the Committee on the Ethics of Animal Experiments of the Tongji Medical College, HUST on 20 September 2021 (approval NO. TJH-202109032, IACUC Number: 2750). All animal experiments were performed in accordance with the Declaration of Helsinki and “Guide for The Care and Use of Laboratory Animals” (NIH publication 86-23 revised 1985). Consent for publication All authors had read and agreed to publish the paper. Competing interests All authors declare that they have no conflict of interests., (© 2024. The Author(s).)

Background: While measuring meniscal extrusion quantitatively is an early risk factor for knee osteoarthritis (KOA), the biomechanics involved in this process are not well understood. This study aimed to investigate the effects of varying degrees of medial and lateral meniscal extrusion and their material softening on knee osteoarthritis progression., Methods: Finite element analysis (FEA) was utilized to simulate varying degrees of meniscal extrusion (1-5 mm) in 72 knee joint models, representing progressive meniscal degeneration and material softening due to injury. Changes in von Mises stress of the cartilage and menisci and the load distribution on the tibial plateau's meniscus and cartilage were studied under balanced standing posture in both healthy and injured knees, and statistical analysis was performed using Spearman correlation., Results: Compared to healthy knees, peak stress in medial compartment tissues increased by over 40% with 4 mm of medial meniscus extrusion, and in lateral compartment tissues with 2 mm of lateral meniscus extrusion. Meniscus extrusion reduced the contact load between the meniscus and femoral cartilage but increased it between the tibial and femoral cartilages, with a maximum increase up to fivefold. Spearman correlation analysis indicated that meniscal extrusion significantly affected peak stress and contact loads in the respective knee compartment (p < 0.001), with a lesser impact on the opposite compartment. Notably, medial meniscal extrusion also significantly increased peak stress in the lateral tibial cartilage (p < 0.05)., Conclusions: The quantitative analysis revealed that meniscal extrusion significantly affected the biomechanics of soft tissues within the same compartment, with limited impact on the opposite side. Specifically, Medial extrusion beyond 4 mm significantly affected the biomechanics of the medial compartment, while lateral extrusion over 2 mm had a similar impact on the lateral compartment. Meniscal softening, without altering joint contact characteristics, primarily affected the biomechanics of the meniscus itself, with minimal impact on other soft tissues., Competing Interests: Declarations Ethics approval and consent to participate This study was carried out in accordance with relevant guide‑lines and regulations and was approved by the committee of The Fifth Affiliated Hospital of Guangzhou Medical University. All the participants provided written informed consent. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Pertussis resurgence has been reported worldwide in the past two decades. Pertussis is still endemic and difficult to control though with universal vaccination in children. The resurgence may be related to multiple variables, such as increased disease awareness and laboratory tests, waning of immunity following vaccination, and/or genetic mutations of Bordetella pertussis. For better pertussis prevention, diagnosis, and management, we called up an expert panel to develop this expert consensus to provide new concepts in diagnosis and treatment for clinical practice., Data Sources: The expert groups collected clinical evidence, summarized their clinical experiences, evaluated preliminary recommendations or guidelines, and then organized open-ended discussions to form the recommendations. This consensus was developed by reviewing the literature and studies in databases, including PubMed, Cochrane, EMBASE, the China Biomedical Database, and the Chinese Journal Full-text Database up to May 2024. The search terms included "pertussis" or "whooping cough", "children", "diagnosis", and "treatment"., Results: The burden of pertussis has also changed from infants to  school children and adults, and these age groups have consequently become the main source of infection for vulnerable population including infants and newborns. In China, a high prevalence of erythromycin-resistant Bordetella pertussis (ERBP) has been reported in the past decade. ERBP may lead to failed clinical empirical treatment with macrolides, which poses a great challenge for pertussis management and control. For better management of pertussis, a flow diagram for diagnosis and treatment of pertussis was presented in this consensus. This consensus also described the diagnostic criteria for pertussis, high-risk cases, and severe pertussis. Macrolides can still be used to treat confirmed erythromycin-sensitive B. pertussis (ESBP) infections, whereas oral trimethoprim-sulfamethoxazole therapy is the initial treatment option for children older than two months. For infants younger than two months, severe patients, or those exhibiting a high degree of sulfonamide allergy, intravenous administration of piperacillin or cefoperazone-sulbactam is advised., Conclusions: This expert consensus provides a comprehensive guidance and a reference for the diagnosis and treatment of pertussis in children., Competing Interests: Declarations Conflict of interest No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article. BGN is a youth editor of World Journal of Pediatrics. The paper was handled by other editor and undergone rigorous peer-review process. Author BGN was not involved in the journal’s review of, or decisions related to, this manuscript. Ethical approval Not required., (© 2024. The Author(s).)

Inherently chiral eight-membered rings embedded in tetraphenylene derivatives and hetero-analogues exhibit unique properties and allow diverse applications. A conceptually viable and straightforward approach to these frameworks is [4+4] cycloaddition, which still remains elusive. In this study, we describe the stereoselective cross-[4+4] cycloaddition of quinone methides (QMs), leading to the formation of oxa-analogues of tetraphenylene with exceptional chemo-, diastereo-, and enantioselectivity. The structures of these novel rigid eight-membered O-heterocycles were explored via single-crystal X-ray diffraction and their stereochemical stability was elaborated through both density functional theory (DFT) calculations and thermal racemization experiments. The developed methodology exhibited broad substrate scope and the resulting cross-[4+4] cycloadducts could be readily transformed into valuable chiral building blocks. Our findings expanded the inherently chiral library of medium-sized rings and also contributed to the advancement of asymmetric cross-[4+4] cycloadditions of quinone methides., (© 2024 Wiley‐VCH GmbH.)

Diabetic foot ulcers (DFUs) are a severe microvascular complication. Platelet-rich plasma (PRP) pitches in DFU treatment. This study explored the mechanism of PRP facilitating wound repair in DFU mice via vascular endothelial growth factor A (VEGFA)/VEGF receptor 2 (VEGFR2)/extracellular signal-regulated kinase (ERK) pathway. The DFU mouse model was established, with wound skin injected with PRP, followed by the detections of wound area, histopathological changes, and CD31-positive cells. IL-6/TNF-α/VEGFA/VEGFR2/p-VEGFR2/(ERK1/2)/(p-ERK1/2) levels in wound tissue homogenates were assessed. VEGFA-VEGFR2 interaction was evaluated. PRP-treated DFU mice were simultaneously treated with fruquintinib/PD98059. PRP reduced wound area, IL-6 and TNF-α levels, elevated epidermal dermal thickness, CD31-positive cell number, and aligned tissue structure, which were mitigated by fruquintinib/PD98059. PRP promoted VEGFR2 phosphorylation. PRP and fruquintinib/PD98059 abated p-VEGFR2/VEGFR2 or p-ERK1/2/ERK1/2 levels in DFU mice. PRP activated the ERK pathway through VEGFA/VEGFR2. Collectively, PRP promoted VEGFR2 phosphorylation and activated the ERK pathway, thereby facilitating wound repair in DFU mice.

Background: Left-behind children(LBC) in rural China are at increased risk for mental health problems, including depression. This study aimed to estimate the prevalence of depression and identify key associate factors among Chinese rural LBC., Methods: A cross-sectional study was conducted using data from 36,612 LBC aged 6 to 18 years old across 596 data collection sites in Nanchong, Sichuan Province, China. Participants completed questionnaires assessing individual factors, family parenting situation, living events, and health-related data. Depression was measured using the Center for Epidemiological Studies-Depression Scale (CES-D). T-tests, chi-square, and logistic regression were performed to identify factors associated with depression., Results: The overall prevalence of depression among LBC was 6.75%. Logistic regression analysis revealed that family parenting situations, such as being from blended families (OR = 1.45) or being cared for by other family members (OR = 1.64), and dissatisfaction with the parenting situation (OR = 1.57) were significantly associated with higher odds of depression. Living events, including being misunderstood (OR = 1.82) and having disputes (OR = 1.48), and health-related factors, such as chronic diseases and regular medication use (OR = 2.38), also increased the risk of depression., Conclusions: This study highlights the high prevalence of depression among Chinese rural LBC and identifies key associate factors, including family parenting situation, negative living events and health-related factors. Targeted interventions and policies addressing these factors are needed to promote the mental health of this vulnerable population., Competing Interests: Declarations Ethics approval and consent to participate The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. All procedures involving human subjects/patients were approved by IRB in Wenzhou Seventh People’s Hospital (EC-KY-2022048). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Small interfering RNA (siRNA) has revolutionised biomedical research and drug development through precise post-transcriptional gene silencing technology. Despite its immense potential, siRNA therapy still faces technical challenges, such as delivery efficiency, targeting specificity, and molecular stability. To address these challenges and facilitate siRNA drug development, we have developed siRNAEfficacyDB, a comprehensive database that integrates experimentally validated siRNA efficacy data. This database contains 3544 siRNA records, covering 42 target genes and 5 cell lines. It provides detailed information on siRNA sequences, target genes, inhibition efficiencies, experimental techniques, cell lines, siRNA concentrations, and incubation times. siRNAEfficacyDB offers a user-friendly web interface that makes it easy to query, browse and analyse data, enabling efficient access to siRNA-related information. In summary, siRNAEfficacyDB provides a useful data foundation for siRNA drug design and optimisation, serving as a valuable resource for advancing computer-aided siRNA design research and nucleic acid drug development. siRNAEfficacyDB is freely available at https://cellknowledge.com.cn/siRNAEfficacy for non-commercial use., (© 2024 The Author(s). IET Systems Biology published by John Wiley & Sons Ltd on behalf of The Institution of Engineering and Technology.)

Aryl ketones are often used as photosensitizers and photoinitiators. Free radical intermediates have been suggested, but not confirmed, to be generated after photoirradiation. Here we found, unexpectedly, that a persistent radical was produced from di-2-pyridyl ketone after UV irradiation, which was detected by the direct ESR method. Interestingly, the persistent radical was very sensitive to oxygen and the pH of the reaction medium. A similar persistent radical was also observed from phenyl-2-pyridyl ketone, but not from 3-benzoylpyridine, 4-benzoylpyridine, and benzophenone, suggesting that the presence of a carbonyl group connected to the ortho -position of the pyridine ring is critical for such radical production. By complementary applications of ESR, HPLC, and ESI-Q-TOF-MS, the possible chemical structures of the persistent radical and final product were identified, and the possible underlying reaction mechanism was proposed. This represents the first report on UV-induced persistent radical generation from 2-pyridyl ketones, which should be of great significance for future studies.

Rationale and Objectives: The early prediction of response to neoadjuvant chemotherapy (NAC) will aid in the development of personalized treatments for patients with breast cancer. This study investigated the value of longitudinal multimodal deep learning (DL) based on breast MR and ultrasound (US) in predicting pathological complete response (pCR) after NAC., Materials and Methods: We retrospectively reviewed the pre-NAC and post-2nd-NAC MR and/or US images of 448 patients enrolled from three centers and extracted DL features from the largest section of the breast tumour using ResNet50. T test, Pearson correlation analysis and least absolute shrinkage and selection operator regression were used to select the most significant DL features for the pre-NAC and post-2nd-NAC MR and US DL models. The stacking model integrates different single-modality DL models and meaningful clinical data. The diagnostic performance of the models was evaluated., Results: In all the patients, the pCR rate was 36.65%. There was no significant difference in diagnostic performance between the different single-modality DL models (DeLong test, p > 0.05). The stacking model integrating the above four DL models with HER2 status yielded areas under the curves of 0.951-0.979, accuracies of 91.55%-92.65%, sensitivities of 90.63%-93.94%, and specificities of 89.47%-94.44% in the cohorts., Conclusion: Longitudinal multimodal DL can be useful in predicting pCR. The stacking model can be used as a new tool for the early noninvasive prediction of the response to NAC, as evidenced by its excellent performance, and therefore aid the development of personalized treatment strategies for patients with breast cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

The photothermal sensitivity of tobacco refers to the degree to which tobacco responds to changes in light and temperature conditions in its growth environment, which is crucial for determining the planting area of cultivars and improving tobacco yield and quality. In order to accurately and effectively evaluate the photothermal sensitivity of tobacco cultivars, this study selected five cultivars and their hybrid combinations with significant differences planted under different ecological conditions from 2021 to 2022 as materials. The experiment was conducted in two locations with significant differences in temperature and light. We measured the agronomic traits and biomass of the experimental materials, and constructed an effective tobacco photothermal sensitivity evaluation model using principal component analysis, membership function, and regression analysis. The reliability of the model was evaluated by utilizing the photosynthetic characteristics, chlorophyll content, and antioxidant enzyme system activity of the experimental materials. The results showed that tobacco biomass is the most important principal component in agricultural traits, and the comprehensive evaluation model for tobacco photothermal sensitivity is: y = 0.4571y 1  + 0.2406y 2  + 0.1725y 3 , where the fitting coefficients R 2 of y 1 , y 2 , and y 3 are 0.945, 0.851, and 0.977, respectively; The photothermal sensitivity of the experimental materials was calculated using this model, and the comprehensive ranking of the 11 experimental materials is: G3 < G5 < G10 < G9 < G11 < G6 < G7 < G2 < G4 < G8 < G1. Conventional identification methods have found that G2, G4, G6, G7, G8, and G11 are sensitive materials, G3, G5, and G10 are insensitive materials, and G1 and G9 are intermediate materials. The consistency rate of the evaluation results of the two methods reached 90.91%. And there is a significant correlation between the agronomic traits selected in the model and the physiological indicators selected by conventional evaluation methods, providing a scientific basis for evaluating the light temperature sensitivity of tobacco cultivars using agronomic traits in this study. The results indicate that the photothermal sensitivity evaluation model established in this study provides an efficient, convenient, and reliable method for evaluating the photothermal sensitivity of tobacco., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Observational studies suggest that hypertension and epilepsy have a high co-occurrence, and antihypertensive medications may have impacts on the prevention and treatment of epilepsy. However, the directionality of causation between them is elusive., Method: By leveraging genome-wide association studies (GWAS) summary data of each trait, we firstly performed bidirectional univariate Mendelian randomization (UVMR) to assess the strength and direction of the associations between pairs of traits, then multivariate MR (MVMR) was conducted to adjust for potential confounders in causalities. Cochran's Q statistics, leave-one-out analysis, MR-Egger regression and MR-Pleiotropy Residual Sum and Outlier methods (MR-PRESSO) were employed to evaluate the robustness of the results. Drug target MR was proceeded to assess the association between five classes of first-line antihypertensive medications and epilepsy. Specifically, single nucleotide polymorphisms (SNPs) extracted from GWAS data on systolic blood pressure (SBP)/diastolic blood pressure (DBP), along with expression quantitative trait loci (eQTL) were utilized as proxies for antihypertensive medications, respectively., Results: Forward UVMR results provided evidence that genetically predicted blood pressure traits and hypertension have causal effects on epilepsy, while reverse UVMR indicated no causal impacts of epilepsy on blood pressure traits or hypertension. The sensitivity analysis results were robust. The causalities between DBP, hypertension and epilepsy remained remarkable after adjustment by MVMR. Inverse-variance-weighted MR (IVW-MR) yielded evidence of positive association only between Beta-Blockers target genes based on DBP GWAS screening and epilepsy. Summary-data-based MR (SMR) identified a positive correlation between Beta-Blockers target gene ADRA1D and epilepsy risk., Conclusions: Hypertension has a causal effect on epilepsy and managing DBP in patients with hypertension through Beta-Blockers may help prevent epilepsy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Nano-pesticides have attracted much attention in the field of agriculture, due to existing problems such as decreased bactericidal effect and poor adhesion. An environmentally friendly metal porphyrin (Cu-TCPP)-based nanocarrier pesticide release of diniconazole (DIN) was designed to enhance bactericidal efficacy and modulate its bioavailability in a multidimensional manner by constructing a metal phenolic network (MPN) encapsulation. The introduction of the MPN prevents the DIN from prematurely escaping from the Cu-TCPP@DIN@MPN in the environment and gives it strong interfacial adhesion to resist rain washing. The resulting Cu-TCPP@DIN@MPN nanoparticles (NPs) showed a lamellar stacked embedded structure, which improved the inhibition of Fusarium oxysporum (90.9%) and photostability (67.2%), while they do not affect healthy plant growth and meet the relevant food safety requirements for DIN residues. This work provides new ideas for the development of superior photostable, adhesive, rainwater erosion-resistant, and sustainable nanocarrier pesticides.

Purpose: We investigated whether homoharringtonine (HHT) added to venetoclax (VEN) plus azacitidine (VA) could improve outcomes and counteract the negative effects of genetic patterns in patients with relapsed/refractory acute myeloid leukemia (RR-AML)., Experimental Design: A multi-center, retrospective, cohort study of the response and genetic patterns of response to the VA plus HHT (VAH) versus the VA regimens as salvage treatment in patients with RR-AML was performed. The endpoints were the rates of composite complete remission (CRc), measurable residual disease (MRD), event-free survival (EFS), overall survival (OS), and relapse between VAH and VA groups., Results: A total of 321 patients (VAH, n=172; VA, n=149) were analyzed. Compared to VA, VAH significantly improved the rates of CRc (44.3% vs. 66.3%, P<0.001), MRD-negativity (34.8% vs. 59.3%, P=0.002), prolonged OS (median: 15.1 months vs. not reached, P <0.001), and EFS (median: 3.8 vs. 13.0 months, P<0.001). VAH significantly mitigated the negative impact on VA efficacy of mutated FLT3-ITD/TKD, N/KRAS, and t(8;21)/AML1-ETO, as well as the relatively unfavorable effects of the TET2 and DNMT3A mutations. VAH significantly enhanced the response of patients with non-adverse European LeukemiaNet (ELN) risk, with a trend towards improved response in those with adverse ELN risk, complex karyotype, and DNMT3A+FLT3+NPM1+. The incidence of grade 3 or higher adverse events was comparable between the two groups., Conclusions: Our findings suggest the addition of HHT to VA might enhance response and mitigate the negative impact of certain genetic patterns in RR-AML while being well tolerated.

Genipin, a precursor of dietary blue pigment, is a promising alternative for industrial applications in food and health. Due to its ability to simultaneously satisfy biosafety requirements and provide crosslinking effects, genipin has attracted considerable attention for food and biomedical applications. In this review, we attempt to shed light on the progress in genipin research using scientometrics. Based on this scientometric discovery, we reviewed the use of genipin-crosslinked films for fruit packaging in food science. Genipin-crosslinked hydrogels used for drug delivery include natural, chemical, and protein delivery systems. Genipin-crosslinked hydrogels for tissue engineering primarily include materials used for tissue regeneration and repair. Genipin-crosslinked hydrogels are used in wound dressings and wound closure. This review provides a scientometric perspective to facilitate future research and development of genipin for food science, drug delivery, tissue engineering, and wound healing., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Disialoganglioside (GD2) is one of the most popular overexpressed antigens for tumor cell targeting. However, GD2-specific antibodies often show unintended targeting to GD2-expressing health-maintaining cells due to the comparable binding affinities both at physiological pH and in a slightly acidic tumor microenvironment (TME). In this work, an affinity-switchable zwitterionic PAMAM G5 dendrimer (G5-3S) is developed for selective binding to GD2 only in a slightly acidic TME. It has 3 sulfonic groups, 128 carboxylic groups, and 125 amino groups on the surface. This affinity switch is realized by multiple hydrogen bond (H-bond) formation between protonated carboxylic groups surrounding a sulfonic group and overexpressed GD2 clusters on the tumor cell membrane in the slightly acidic TME, whereas there is no stable H-bond formation at physiological pH. Thus, G5-3S shows superior selectivity to GD2-overexpressed tumor cells over anti-GD2 antibodies by avoiding targeting GD2-expressing health-maintaining cells at physiological pH. This suggests that G5-3S is a promising candidate for GD2-overexpressed cancer treatment.

Phyllanthi Fructus, known as Yuganzi (YGZ), is a unique medicine and food homologous fruit with both medicinal and nutritional properties. Its historical use in treating hyperuricemia (HUA) and gout is well-documented. However, the precise therapeutic effects and potential molecular mechanisms remain unclear. In this study, an experimental rat modelling by a high-fat/high-sugar diet and potassium oxonate/adenine oral administration was used to evaluate the pharmacodynamic effects of YGZ. Network pharmacology, molecular docking and molecular dynamics simulation were utilized to elucidate the potential mechanisms. Supplementation with YGZ effectively ameliorated HUA by inhibiting xanthine oxidase activity, and enhancing uric acid excretion through up-regulating of OAT1 and ABCG2, while down-regulating of URAT1. Furthermore, YGZ supplementation enhanced superoxide dismutase activity, reduced malondialdehyde content, and inhibited the secretion of IL1B, IL6, TNFα, ICAM1, VCAM1, TGFβ1, and NF-κB protein expression. Network pharmacology analysis indicated that YGZ influences 138 targets, modulating the disease network via lipid and atherosclerosis, insulin resistance, HIF-1, TNF, IL-17, TLRS, and NF-κB signaling pathways. Molecular docking analysis suggested that organic acids (e.g. ellagic acid, gallic acid) and flavonoids (e.g. quercetin, delphinidin, luteolin, epigallocatechin gallate) exhibited superior binding abilities to key targets (e.g. XDH, ABCG2, URAT1, OAT1, IRS1, PTGS2, TLR4). Noteworthy, molecular dynamics simulations confirmed that epigallocatechin gallate binds to URAT1 with the greatest stability. These results provide substantial evidence for the therapeutic efficacy of YGZ and establish a theoretical foundation for the development of natural products in treating hyperuricemia., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Rationale: Etomidate is a short-acting general anesthetic for clinical use and has been used as alternative to propofol or added to the powdered drug and e-cigarette cartridges recently, leading to an increase in abuse. But there have been no studies conducted on the abuse potential of etomidate., Objectives and Methods: This study aimed to evaluate the abuse potential of etomidate via conditioned place preference (CPP) and self-administration tests, reflecting its rewarding and reinforcing effects. In addition, righting reflex and open-field tests were conducted to evaluate the anesthetic and sedative effects of etomidate., Results: In male mice, the ED 50 after intraperitoneal (i.p.) injection of anesthetic effect for etomidate was 9.156 mg/kg and the ED 50 of the sedative effect 5 min after intraperitoneal injection was 2.389 mg/kg. Etomidate induced CPP in male mice at the minimum dose of 3 mg/kg i.p. and supported stable self-administration in male rats at the dose of 0.075 mg/kg/intravenous infusion. The dose-response curve of etomidate was an inverted U-shape, which showed significant self-administrations compared with the vehicle group at doses of 0.05-0.1 mg/kg/infusion etomidate and the highest intake of 21.1 ± 0.64 infusions per 4 h-session., Conclusions: These results clearly demonstrate that etomidate has rewarding and reinforcing effects in male rodents, as well as effects on anesthesia and motor inhibition. These findings indicate the possibility of abuse potential in humans using etomidate., Competing Interests: Declarations Ethics approval and consent to participate All procedures followed the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Conflict of interest The authors declare no conflict of interest related to this work., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: While Parkinsonism plus syndrome (PPS) is one of several atypical manifestations in neurosyphilis patients, its clinical features and brain-related manifestations are inadequately documented. In this cross-sectional study, we endeavored to indicate some key clinical and imaging features of neurosyphilis patients, particularly those specific to PPS., Methods: We retrospectively included all syphilis patients enrolled in the study from January 2021 to February 2024. All in all, 54 neurosyphilis patients with PPS were recruited. Their socio-demographical features, clinical status, presentations, laboratory manifestations and neuroimaging were analyzed retrospectively., Results: The predominant phenotype was general paresis (GP). Median age at onset was 50 years, and 87.0 % of the patients were male. Bradykinesia (53.7 %) was the most common manifestation of PPS in neurosyphilis patients. The most frequent physical sign was orofacial dyskinesia (the Candy sign), which accounted for 51.9 % of cases. In nearly three quarters (71.1 %), magnetic resonance imagery revealed temporal, hippocampal lobe, or whole brain atrophy, while 13.3 % exhibited basal ganglia lacunar infarction, and 22.2 % cases had focal demyelination in the cerebral peduncle, cerebellum, frontal lobe, parietal lobe, hippocampus and/or lateral vertical., Conclusions: Neurosyphilis patients exhibited PPS in involving bradykinesia, tremor rigidity and, in most cases, GP. Brain atrophy and basal ganglia lesion were the most common imaging findings in neurosyphilis patients with PPS. Our results should help to elucidate PPS characteristics PPS and neuroimaging mechanisms in neurosyphilis patients with PPS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

BACKGROUND Anterior hip dislocation is a rare injury that often occurs following high-energy road traffic accidents and accounts for approximately 7% to 13% of all hip dislocations. This report describes the presentation, diagnosis, and treatment of a 44-year-old woman with anterior hip dislocation and multiple comminuted fractures due to a vehicular crush injury. A PubMed search showed no similar cases have been reported in the English literature. CASE REPORT A 44-year-old woman was urgently seen at a local hospital after being run over twice by the rear wheel of a reversing truck while walking. Radiographic examination revealed right obturator-type anterior hip dislocation and multiple injuries. Pelvic external fixation and right femoral supracondylar bone traction were performed. Subsequent to hemodynamic stabilization, the patient was transferred to our hospital. Five days later, open reduction internal fixation was performed. Anterior pelvic ring internal fixation was performed after 20 days. The patient was hospitalized for 33 days. At the 5-year postoperative follow-up, the CT image showed healing. There was no lumbar or hip pain, and the patient had returned to normal life and work. CONCLUSIONS Anterior hip dislocation combined with bilateral obturator fractures, sacral fractures, lumbar fractures, and thoraco-abdominal injuries are rare in clinical practice. It is crucial to correctly handle multiple injuries to achieve enhanced recovery after surgery and prevent complications. The aim of this study is to document the clinical presentation, management, and outcomes of this unique case, highlighting the challenges and potential complications associated with femoral head displacement toward the obturator foramen.

Tomato (Solanum lycopersicum L.) is an important model plant species in photomorphogenesis research. Ultraviolet B (UV-B) induces the dissociation of homodimers of the photoreceptor UV RESISTANCE LOCUS8 (UVR8) into monomers, which translocate into the nucleus. Nuclear accumulation of UVR8 is a prerequisite for its signaling function. Previous studies have reported that SUPPRESSOR OF PHYTOCHROME A-105 (SPA) family members may regulate UV-B signaling in Arabidopsis (Arabidopsis thaliana); however, the underlying mechanism is unknown. Here, we show that the tomato genome encodes four SPA (SlSPA) orthologs. Genome-edited Slspa3 mutants exhibited enhanced photomorphogenic responses in white light, suggesting that SlSPA3 inhibits general photomorphogenesis. By contrast, UVR8-mediated gene expression in response to UV-B was compromised in Slspa3 mutants, suggesting that SlSPA3 promotes UV-B signaling. UV-B-induced nuclear accumulation of UVR8, which is essential for UV-B signaling, was reduced in the Slspa3 mutants. Moreover, UV-B-induced nuclear accumulation of UVR8 was also reduced in the Arabidopsis spa1 spa2 spa3 and spa1 spa2 spa4 triple mutants, indicating a conserved mechanism in these two species. Notably, spa1 spa2 spa4 exhibited normal UV-B-induced interaction between UVR8 and the plant morphogenesis repressor CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1). This suggests that the well-established mechanisms of UVR8 nuclear retention remained unaffected in spa1 spa2 spa4. Thus, our work uncovered a potentially unrecognized mechanism by which SPA proteins regulate UV-B signaling through the promotion of UVR8 nuclear abundance in land plants., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

The increasing use of antibiotics has attracted widespread attention to their environmental risks. However, the phototoxicity of sulfonamide antibiotics to plants remain unclear. In this study, the mechanism of the effect of sulfamethoxazole on photosynthesis of pakchoi cabbage (Brassica rapa var. chinensis) was investigated. The results showed that sulfamethoxazole inhibited the growth of pakchoi cabbage and produced photosynthetic toxicity. The growth inhibition rates increased with concentration, the root and shoot weight were 76.02 % and 47.04 % of the control, respectively, with stay-greens phenomenon in 4 mg·L -1 sulfamethoxazole treatment. Chlorophyll precursors (protoporphyrin IX (Proto IX), Mg-proto IX, and protochlorophyllide (Pchlide), 5-aminolevulinic acid (ALA), and porphobilinogen (PBG)) were 1.38-, 1.26-, 1.12-, 1.71-, and 0.96-fold of the control, respectively; photosynthetic pigments (chlorophyll a, chlorophyll b, and carotenoids) were 1.26-, 1.39-, and 1.03-fold of the control, respectively. Respiration rate was 271.42 % of the control, whereas the net photosynthetic rate was 50.50 % of the control. The maximum photochemical quantum yield of PSII (F v /F m ), the actual photosynthetic efficiency (Y(II)), the quantum yield of non-regulated energy dissipation (Y(NO)), the apparent electron transfer efficiency of PSII (ETR) under actual light intensity were affected, and chloroplast swelling was observed. Proteomic analysis showed that photosynthesis-related pathways were significantly up-regulated, biological processes such as light response, carbohydrates, and reactive oxygen species were activated. Metabolomic analysis revealed that the tricarboxylic acid cycle (TCA cycle) and carbohydrate catabolism were stimulated significantly (p < 0.05), sugars and amino acids were increased to regulate and enhance the resilience of photosynthesis. While folate biosynthesis and ribosomal pathways were significantly down-regulated, the synthesis and translation processes of amino acids and nucleotides were inhibited., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Immune checkpoint inhibitor (ICI)-associated myocarditis is a rare but potentially fatal immune-related adverse event. Previously, we reported a case of ICI-associated myocarditis with elevated autoantibodies to 4E-binding protein 3 (4E-BP3). Recent studies have suggested that 4E-BP3 may play an important role in tumor development. However, its role in cardiac diseases including myocarditis is unknown. We investigated the role of 4E-BP3 in an autoimmune myocarditis mouse model. Myocarditis was induced in wild-type and 4E-BP3 knockout mice by immunization with murine α-myosin peptide. 4E-BP3 gene expression was upregulated in the heart of myocarditis mouse. We found that genetic deletion of 4E-BP3 attenuated myocardial inflammation, reduced fibrosis area, and improved cardiac function in myocarditis mice. Studies in bone marrow-chimeric mice demonstrated that immune cell-derived 4E-BP3 plays a pivotal role in the pathogenesis of myocarditis. Immune cell transfer experiments revealed that 4E-BP3 deficiency in dendritic cells and CD4 + T cells decreased disease severity in recipient mice. Furthermore, dendritic cells that were deficient in 4E-BP3 exhibited a diminished capacity to produce IL-6 and IL-1β. Naive CD4 + T cells lacking 4E-BP3 had a reduced ability to differentiate into T-helper (Th)1 and Th17 cells. These findings suggest that 4E-BP3 in dendritic cells and CD4 + T cells may be critically involved in the pathogenesis of α-myosin-specific T cell-mediated myocarditis. Thus, 4E-BP3 could be a possible therapeutic target for myocarditis., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Sun-loving plants undergo shade avoidance syndrome (SAS) to compete with their neighbors for sunlight in shade conditions. Phytochrome B (phyB) plays a dominant role in sensing the shading signals (low red to far-red ratios) and triggering SAS. Shade drives phyB conversion to inactive form, consequently leading to the accumulation of PHYTOCHROMEINTERACTING FACTOR 4 (PIF4) that promotes plant growth. Here, we show B-box PROTEIN 7 (BBX7)/BBX8 and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1)/LATE ELONGATED HYPOCOTYL (LHY) positively regulate the low R : FR-induced PIF4 expression and promote the low R : FR-triggered hypocotyl growth in Arabidopsis. Shade interferes the interactions of phyB with BBX7 or BBX8 and triggers the accumulation of BBX7 and BBX8 independent of phyB. BBX7 and BBX8 associate with CCA1 and LHY to activate their transcription, the gene produces of which subsequently upregulate the expression of PIF4 in shade. Genetically, BBX7 and BBX8 act upstream of CCA1, LHY, and PIF4 with respect to hypocotyl growth in shade conditions. Our study reveals the BBX7/8-CCA1/LHY transcription factor cascade upregulates PIF4 expression and increases its abundance to promote plant growth and development in response to shade., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation.)

Background: Neuropsychiatric manifestations, such as cognitive impairment, are relatively prevalent in systemic sclerosis (SSc) patients. This study aimed to investigate the resting state (RS) functional alternations of SSc patients and the potential influenced factors., Methods: Forty-four SSc patients (mean age, 46.3 ± 11.4 years; 40 females) and 19 age and sex comparable healthy volunteers (mean age, 42.6 ± 11.3 years; 16 females) were recruited and underwent RS functional MR imaging (fMRI) and neuropsychological assessments. Functional segregation analysis was performed to calculate the amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo). Functional integration analysis was conducted using group independent component analysis to calculate intra-network and inter-network functional connectivity (FC). The fMRI measurements were compared between SSc patients and healthy volunteers using voxel-based pairwise two-sample t-tests. The correlations between clinical characteristics and fMRI measurements were also analyzed., Results: Compared to healthy volunteers, SSc patients exhibited significantly decreased ALFF and increased ReHo (all P < 0.01, FWE corrected). SSc patients predominantly showed decreased intra-network and inter-network FC in the auditory network, visual network, default mode network, frontoparietal network and attention network (intra-network FC: P < 0.01, uncorrected, cluster size > 30; inter-network FC: P < 0.05, FDR correction). Furthermore, clinical characteristics including disease duration (r value ranged from - 0.31 to 0.36), elevated erythrocyte sedimentation rate (r = 0.35), Montreal Cognitive Assessment score (r = 0.43), and Hamilton Depression Scale score (r = -0.40) were significantly associated with fMRI measurements (all P < 0.05)., Conclusions: Spontaneous activity and functional connectivity alternations can be seen in SSc patients, which are partially associated with neuropsychiatric manifestations and tend to aggravate with disease duration., (© 2024. The Author(s).)