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Monitoring spores is crucial for predicting and preventing fungal- or oomycete-induced diseases like grapevine downy mildew. However, manual spore or sporangium detection using microscopes is time-consuming and labor-intensive, often resulting in low accuracy and slow processing speed. Emerging deep learning models like YOLOv8 aim to rapidly detect objects accurately but struggle with efficiency and accuracy when identifying various sporangia formations amidst complex backgrounds. To address these challenges, we developed an enhanced YOLOv8s, namely, AFM-YOLOv8s, by introducing an Adaptive Cross Fusion module, a lightweight feature extraction module FasterCSP (Faster Cross-Stage Partial Module), and a novel loss function MPDIoU (Minimum Point Distance Intersection over Union). AFM-YOLOv8s replaces the C2f module with FasterCSP, a more efficient feature extraction module, to reduce model parameter size and overall depth. In addition, we developed and integrated an Adaptive Cross Fusion Feature Pyramid Network to enhance the fusion of multiscale features within the YOLOv8 architecture. Last, we utilized the MPDIoU loss function to improve AFM-YOLOv8s' ability to locate bounding boxes and learn object spatial localization. Experimental results demonstrated AFM-YOLOv8s' effectiveness, achieving 91.3% accuracy (mean average precision at 50% IoU) on our custom grapevine downy mildew sporangium dataset-a notable improvement of 2.7% over the original YOLOv8 algorithm. FasterCSP reduced model complexity and size, enhanced deployment versatility, and improved real-time detection, chosen over C2f for easier integration despite minor accuracy trade-off. Currently, the AFM-YOLOv8s model is running as a backend algorithm in an open web application, providing valuable technical support for downy mildew prevention and control efforts and fungicide resistance studies., (Copyright © 2024 Changqing Yan et al.)

Introduction: Primary cilia are hair-like solitary organelles growing on most mammalian cells that play fundamental roles in embryonic patterning and organogenesis. Defective cilia often cause a suite of inherited diseases called ciliopathies with multifaceted manifestations. Intraflagellar transport (IFT), a bidirectional protein trafficking along the cilium, actively facilitates the formation and absorption of primary cilia. IFT172 is the largest component of the IFT-B complex, and its roles in Bardet-Biedl Syndrome (BBS) have been appreciated with unclear mechanisms., Objectives: We performed a battery of behavioral tests with Ift172 haploinsufficiency (Ift172 +/- ) and WT littermates. We use RNA sequencing to identify the genes and signaling pathways that are differentially expressed and enriched in the hippocampus of Ift172 +/- mice. Using AAV-mediated sparse labeling, electron microscopic examination, patch clamp and local field potential recording, western blot, luciferase reporter assay, chromatin immunoprecipitation, and neuropharmacological approach, we investigated the underlying mechanisms for the aberrant phenotypes presented by Ift172 +/- mice., Results: Ift172 +/- mice displayed excessive self-grooming, elevated anxiety, and impaired cognition. RNA sequencing revealed enrichment of differentially expressed genes in pathways relevant to axonogenesis and synaptic plasticity, which were further confirmed by less spine density and synaptic number. Ift172 +/- mice demonstrated fewer parvalbumin-expressing neurons, decreased inhibitory synaptic transmission, augmented theta oscillation, and sharp-wave ripples in the CA1 region. Moreover, Ift172 haploinsufficiency caused less BDNF production and less activated BDNF-TrkB signaling pathway through transcription factor Gli3. Application of 7,8-Dihydroxyflavone, a potent small molecular TrkB agonist, fully restored BDNF-TrkB signaling activity and abnormal behavioral phenotypes presented by Ift172 +/- mice. With luciferase and chip assays, we provided further evidence that Gli3 may physically interact with BDNF promoter I and regulate BDNF expression., Conclusions: Our data suggest that Ift172 per se drives neurotrophic effects and, when defective, could cause neurodevelopmental disorders reminiscent of autism-like disorders., 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. Production and hosting by Elsevier B.V.)

Lenvatinib is a multiple receptor tyrosine kinases inhibitor (TKI) authorized for first-line treatment of hepatocellular carcinoma (HCC). However, Lenvatinib resistance is common in HCC clinical treatment, highlighting the urgent need to understand mechanisms of resistance. Here, we identified Golgi membrane protein 1 (GOLM1), a type II transmembrane protein originally located in the Golgi apparatus, as a novel regulator of Lenvatinib resistance. We found GOLM1 was overexpressed in Lenvatinib resistant human HCC cell lines, blood and HCC samples. Additionally, GOLM1 overexpression contributes to Lenvatinib resistance and HCC progression in vitro and in vivo. Mechanistically, GOLM1 upregulates CSN5 expression through EGFR-STAT3 pathway. Reversely, CSN5 deubiquitinates and stabilizes GOLM1 protein by inhibiting ubiquitin-proteasome pathway of GOLM1. Furthermore, clinical specimens of HCC showed a positive correlation between the activation of the GOLM1-EGFR-STAT3-CSN5 axis. Finally, GOLM1 knockdown was found to act in synergy with Lenvatinib in subcutaneous and orthotopic mouse model. Overall, these findings identify a mechanism of resistance to Lenvatinib treatment for HCC, highlight an effective predictive biomarker of Lenvatinib response in HCC and show that targeting GOLM1 may improve the clinical benefit of Lenvatinib., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

This work aimed to explore the changes of rice protein (RP) in solubility, emulsifying properties, and antioxidant activity after the enzyme hydrolysis-assisted fibrillation dual modification. Results showed that enzyme hydrolysis by papain and fibrillation treatments significantly affected the secondary and tertiary structures of RP. The modified proteins, including RP hydrolysate (RPH), RP nanofibrils (RPN), and RPH nanofibrils (RPHN), demonstrated enhanced solubility and antioxidant activity compared to RP, with RPHN exhibiting the superior performance. The emulsifying capacity of RPH, RPN, and RPHN increased by 9.55 %, 22.86 %, and 26.57 %, respectively, compared to that of RP. Furthermore, RPHN displayed the highest emulsion stability index. Nanoemulsion stabilized by RPHN showed enhanced centrifugal, storage, and oxidative stabilities. Neither RPHN nor RPN exhibited cytotoxicity to human cell lines, and could provide nutrients for cells. Overall, the functional properties and antioxidant activity of RP were significantly improved by enzyme hydrolysis-assisted fibrillation dual modification. This study may provide reference for the development and utilization of nanofibrils from plant proteins., 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.)

Background and Purpose: The emerging antidepressant effects of ketamine have inspired tremendous interest in its underlying neurobiological mechanisms, although the involvement of 5-HT in the antidepressant effects of ketamine remains unclear., Experimental Approach: The chronic restraint stress procedure was performed to induce depression-like behaviours in mice. OFT, FST, TST, and NSFT tests were used to evaluate the antidepressant-like effects of ketamine. Tph2 knockout or depletion of 5-HT by PCPA and 5,7-DHT were used to manipulate the brain 5-HT system. ELISA and fibre photometry recordings were used to measure extracellular 5-HT levels in the brain., Key Results: 60 min after injection, ketamine (10 mg·kg -1 , i.p.) produced rapid antidepressant-like effects and increased brain 5-HT levels. After 24 h, ketamine significantly reduced immobility time in TST and FST tests and increased brain 5-HT levels, as measured by ELISA and fibre photometry recordings. The sustained (24 h) but not rapid (60 min) antidepressant-like effects of ketamine were abrogated by PCPA and 5,7-DHT, or by Tph2 knockout. Importantly, NBQX (10 mg·kg -1 , i.p.), an AMPA receptor antagonist, significantly inhibited the effect of ketamine on brain 5-HT levels and abolished the sustained antidepressant-like effects of ketamine in naïve or CRS-treated mice., Conclusion and Implications: This study confirms the requirement of serotonergic neurotransmission for the sustained antidepressant-like effects of ketamine, which appears to involve AMPA receptors, and provides avenues to search for antidepressant pharmacological targets., (© 2024 British Pharmacological Society.)

The human gut microbiota significantly impacts health, including liver conditions like liver cirrhosis (LC) and spontaneous bacterial peritonitis (SBP). Immunoglobulin A (IgA) plays a central role in maintaining gut microbial balance. Understanding IgA's interplay with gut microbiota and liver health is crucial. This study explores the relationship between fecal IgA levels, gut microbiota, and liver injury severity. A total of 69 LC patients and 30 healthy controls were studied. Fecal IgA levels were measured using ELISA, and IgA-coated bacteria were quantified via flow cytometry. Microbiota diversity and composition were assessed through 16S rRNA sequencing. Liver injury severity was graded using the Child-Pugh score. Statistical analyses determined correlations. LC patients had higher fecal IgA levels than controls, correlating positively with liver injury severity. Microbiota diversity decreased with severity, accompanied by shifts in composition favoring pro-inflammatory species. Ralstonia abundance positively correlated with liver injury, whereas Faecalibacterium showed a negative correlation. Specific microbial markers for SBP were identified. Functional profiling revealed altered microbial functionalities in LC and SBP. Elevated fecal IgA levels, coupled with microbiota alterations, correlate with liver injury severity in LC patients. Modulating gut microbiota could be a promising strategy for managing liver-related conditions. Further research is needed to understand underlying mechanisms and translate findings into clinical practice, potentially improving patient outcomes., (© 2024 The Author(s). The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Nitric oxide (NO) and reactive oxygen species (ROS) embody excellent potential in cancer therapy. However, as a small molecule, their targeted delivery and precise, controllable release are urgently needed to achieve accurate cancer therapy. In this paper, a novel US-responsive bifunctional molecule (SD) and hyaluronic acid-modified MnO 2 nanocarrier was developed, and a US-responsive NO and ROS controlled released nanoplatform was constructed. US can trigger SD to release ROS and NO simultaneously at the tumor site. Thus, SD served as acoustic sensitizer for sonodynamic therapy and NO donor for gas therapy. In the tumor microenvironment, the MnO 2 nanocarrier can effectively deplete the highly expressed GSH, and the released Mn 2+ can make H 2 O 2 to produce . OH by Fenton-like reaction, which exhibited a strong chemodynamic effect. The high concentration of ROS and NO in cancer cell can induce cancer cell apoptosis ultimately. In addition, toxic ONOO - , which was generated by the reaction of NO and ROS, can effectively cause mitochondrial dysfunction, which induced the apoptosis of tumor cells. The 131 I was labeled on the nanoplatform, which exhibited internal radiation therapy for tumor therapy. In -vitro and -vivo experiments showed that the nanoplatform has enhanced biocompatibility, and efficient anti-tumor potential, and it achieves synergistic sonodynamic/NO/chemodynamic/radionuclide therapy for 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 Elsevier Inc. All rights reserved.)

Raman spectroscopy has become an important single-cell analysis tool for monitoring biochemical changes at the cellular level. However, Raman spectral data, typically presented as continuous data with high-dimensional characteristics, is distinct from discrete sequences, which limits the application of deep learning-based algorithms in data analysis due to the lack of discretization. Herein, a model called fragment-fusion transformer is proposed, which integrates the discrete fragmentation of continuous spectra based on their intrinsic characteristics with the extraction of intrafragment features and the fusion of interfragment features. The model integrates the intrinsic feature-based fragmentation of spectra with transformer, constructing the fragment transformer block for feature extraction within fragments. Interfragment information is combined through the pyramid design structure to improve the model's receptive field and fully exploit the spectral properties. During the pyramidal fusion process, the information gain of the final extracted features in the spectrum has been enhanced by a factor of 9.24 compared to the feature extraction stage within the fragment, and the information entropy has been enhanced by a factor of 13. The fragment-fusion transformer achieved a spectral recognition accuracy of 94.5%, which is 4% higher compared to the method without fragmentation and fusion processes on the test set of cell Raman spectroscopy identification experiments. In comparison to common spectral classification models such as KNN, SVM, logistic regression, and CNN, fragment-fusion transformer has achieved 4.4% higher accuracy than the best-performing CNN model. Fragment-fusion transformer method has the potential to serve as a general framework for discretization in the field of continuous spectral data analysis and as a research tool for analyzing the intrinsic information within spectra.

The development of the pancreatic head originates from the fusion of the ventral and dorsal pancreatic primordia during embryonic development. Theoretically, the origin of pancreatic head cancer also exists from the ventral pancreas and the dorsal pancreas. Among 49 patients with pancreatic head cancer, pancreatic head cancer was divided into pancreatic head cancer originating from the ventral (PHCv) or dorsal pancreas (PHCd) through imaging and pathological classification. The clinical data was collected and compared between the PHCv group and the PHCd group. The results showed that the patients from the PHCd group had worse long-term survival than those from the PHCv group (10 months vs 14.5 months). Similarly, the progression-free survival (PFS) results also indicate that patients from the PHCd group had a shorter time than those from the PHCv group (5 months vs 9.5 months). Further stratified analysis of potentially related factors showed that microvascular invasion is related to poor prognosis, and patients with pancreatic head cancer derived from the dorsal pancreas are more likely to develop microvascular invasion., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Bee products, abundant in bioactive ingredients, have been utilized in both traditional and contemporary medicine. Their antioxidant, antimicrobial, and anti-inflammatory properties make them valuable for food, preservation, and cosmetics applications. Honeybees are a vast reservoir of potentially beneficial products such as honey, bee pollen, bee bread, beeswax, bee venom, and royal jelly. These products are rich in metabolites vital to human health, including proteins, amino acids, peptides, enzymes, sugars, vitamins, polyphenols, flavonoids, and minerals. The advancement of nanotechnology has led to a continuous search for new natural sources that can facilitate the easy, low-cost, and eco-friendly synthesis of nanomaterials. Nanoparticles (NPs) are actively synthesized using honeybee products, which serve dual purposes in preventive and interceptive treatment strategies due to their richness in essential metabolites. This review aims to highlight the potential role of bee products in this line and their applications as catalysts and food preservatives and to point out their anticancer, antibacterial, antifungal, and antioxidant underlying impacts. The research used several online databases, namely Google Scholar, Science Direct, and Sci Finder. The overall findings suggest that these bee-derived substances exhibit remarkable properties, making them promising candidates for the economical and eco-friendly production of NPs.

Continuous dynamic recrystallization (CDRX) is widely acknowledged to occur during hot forming and plays a significant role in microstructure development in alloys with moderate to high stacking fault energy. In this work, the flow stress and CDRX behaviors of the TC18 alloy subjected to hot deformation across a wide range of processing conditions are studied. It is observed that deformation leads to the formation of new low-angle grain boundaries (LAGBs). Subgrains rotate by absorbing dislocations, resulting in an increase in LAGB misorientation and the transition of some LAGBs into high-angle grain boundaries (HAGBs). The HAGBs migrate within the material, assimilating the (sub)grain boundaries. Subsequently, an internal state variable (ISV)-based CDRX model is developed, incorporating parameters such as the dislocation density, adiabatic temperature rise, subgrain rotation, LAGB area, HAGB area, and LAGB misorientation angle distribution. The values of the correlation coefficient (R), relative average absolute error (RAAE), and root-mean-square error (RMSE) between the anticipated true stress and measured stress are 0.989, 6.69%, and 4.78 MPa, respectively. The predicted outcomes demonstrate good agreement with experimental findings. The evolving trends of the subgrain boundary area under various conditions are quantitatively analyzed by assessing the changes in dynamic recovery (DRV)-eliminated dislocations and misorientation angles. Moreover, the ISV-based model accurately predicts the decreases in grain and crystallite sizes with higher strain rates and lower temperatures. The projected outcomes also indicate a transition from a stable and coarse-grained microstructure to a continuously recrystallized substructure.

Porphyromonas gingivalis has been demonstrated to have the strongest association with periodontitis. Within the host, P. gingivalis relies on acquiring iron and heme through the aggregation and lysis of erythrocytes, which are important factors in the growth and virulence of P. gingivalis . Additionally, the excess obtained heme is deposited on the surface of P. gingivalis , protecting the cells from oxidative damage. Based on these biological properties of the interaction between P. gingivalis and erythrocytes, this study developed an erythrocyte membrane nanovesicle loaded with gallium porphyrins to mimic erythrocytes. The nanovesicle can target and adhere with P. gingivalis precisely, being lysed and utilized by P. gingivalis as erythrocytes. Ingested gallium porphyrin replaces iron porphyrin in P. gingivalis , causing intracellular metabolic disruption. Deposited porphyrin generates a large amount of reactive oxygen species (ROS) under blue light, causing oxidative damage, and its lethality is enhanced by bacterial metabolic disruption, synergistically killing P. gingivalis . Our results demonstrate that this strategy can target and inhibit P. gingivalis , reduce its invasion of epithelial cells, and alleviate the progression of periodontitis.

XPO1 is an attractive and promising therapeutic target frequently overexpressed in multiple hematological malignancies. The clinical use of XPO1 inhibitors in natural killer/T-cell lymphoma (NKTL) is not well documented. Here, we demonstrated that XPO1 overexpression is an indicator of poor prognosis in patients with NKTL. The compassionate use of the XPO1 inhibitor selinexor in combination with chemotherapy showed favorable clinical outcomes in three refractory/relapsed (R/R) NKTL patients. Selinexor induced complete tumor regression and prolonged survival in sensitive xenografts but not in resistant xenografts. Transcriptomic profiling analysis indicated that sensitivity to selinexor was correlated with deregulation of the cell cycle machinery, as selinexor significantly suppressed the expression of cell cycle-related genes. CDK4/6 inhibitors were identified as sensitizers that reversed selinexor resistance. Mechanistically, targeting CDK4/6 could enhance the anti-tumor efficacy of selinexor via the suppression of CDK4/6-pRb-E2F-c-Myc pathway in resistant cells, while selinexor alone could dramatically block this pathway in sensitive cells. Overall, our study provids a preclinical proof-of-concept for the use of selinexor alone or in combination with CDK4/6 inhibitors as a novel therapeutic strategy for patients with R/R NKTL., 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 B.V. All rights reserved.)

Neurological symptoms are central to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), yet its underlying neurophysiological mechanisms remain elusive. We examined a neglected aspect of task-based functional MRI, focusing on how blood oxygenation level-dependent (BOLD) signals alter during cognitive tasks in ME/CFS. This prospective observational study utilised MRI scans on ME/CFS participants and healthy controls (HCs) with sedentary lifestyles (ACTRN12622001095752). Participants completed two blocks of a Symbol Digit Modalities Test, with 30 trials per block split into two sets. The fMRI signal changes between blocks and sets were compared within and between groups. Thirty-four ME/CFS participants (38 years ± 10; 27 women) and 34 HCs (38 ± 10; 27 women), were evaluated. In the second task block, ME/CFS participants exhibited increased activation in the right postcentral gyrus, contrasting with decreased activation in multiple regions in HCs. These results were further confirmed by significantly higher bilateral dynamic changes (2nd vs 1st set) in the motor, sensory and cognitive cortex in ME/CFS compared to HCs and significant correlations between those changes in the left primary motor cortex with fatigue severities. BOLD adaptation, potentially improving energy economy, was absent in ME/CFS, which may provide an underlying neurophysiological process in ME/CFS., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aqueous Zn-ion batteries are an attractive electrochemical energy storage solution for their budget and safe properties. However, dendrites and uncontrolled side reactions in anodes detract the cycle life and energy density of the batteries. Grain boundaries in metals are generally considered as the source of the above problems but we present a diverse result. This study introduces an ultra-high proportion of grain boundaries on zinc electrodes through femtosecond laser bombardment to enhance stability of zinc metal/electrolyte interface. The ultra-high proportion of grain boundaries promotes the homogenization of zinc growth potential, to achieve uniform nucleation and growth, thereby suppressing dendrite formation. Additionally, the abundant active sites mitigate the side reactions during the electrochemical process. Consequently, the 15 μm Fs-Zn||MnO 2 pouch cell achieves an energy density of 249.4 Wh kg -1 and operates for over 60 cycles at a depth-of-discharge of 23 %. The recognition of the favorable influence exerted by UP-GBs paves a new way for other metal batteries., (© 2024 Wiley-VCH GmbH.)

Fungi are key decomposers of deadwood, but the impact of anthropogenic changes in nutrients and temperature on fungal community and its consequences for wood microbial respiration are not well understood. Here, we examined how nitrogen and phosphorus additions (field experiment) and warming (laboratory experiment) together influence fungal composition and microbial respiration from decomposing wood of angiosperms and gymnosperms in a subtropical forest. Nutrient additions significantly increased wood microbial respiration via fungal composition, but effects varied with nutrient types and taxonomic groups. Specifically, phosphorus addition significantly increased wood microbial respiration (65%) through decreased acid phosphatase activity and increased abundance of fast-decaying fungi (e.g., white rot), while nitrogen addition marginally increased it (30%). Phosphorus addition caused a greater increase in microbial respiration in gymnosperms than in angiosperms (83.3% vs. 46.9%), which was associated with an increase in Basidiomycota:Ascomycota operational taxonomic unit abundance in gymnosperms but a decrease in angiosperms. The temperature dependencies of microbial respiration were remarkably constant across nutrient levels, consistent with metabolic scaling theory hypotheses. This is because there was no significant interaction between temperature and wood phosphorus availability or fungal composition, or the interaction among the three factors. Our results highlight the key role of tree identity in regulating nutrient response of wood microbial respiration through controlling fungal composition. Given that the range of angiosperm species may expand under climate warming and forest management, our data suggest that expansion will decrease nutrient effects on forest carbon cycling in forests previously dominated by gymnosperm species., (© 2024 The Ecological Society of America.)

The impact of different forms of dietary fiber (total, insoluble or soluble) derived from the same source on health remains incompletely understood. In this study, the effects of total, insoluble, and soluble dietary fiber extracted from highland barley (HDF, HIDF, and HSDF) on combating obesity were evaluated and compared. A high-fat diet (HFD) was used to induce obesity in a murine model, followed by gavage administration of HDF, HIDF, or HSDF, and a comprehensive multi-omics approach was utilized to assess and compare the effects of these dietary fibers on obesity-related parameters. The results showed that all three dietary fibers significantly reduced body weight, modified blood lipid profiles, and ameliorated tissue damage in HFD-fed mice. Additionally, 16S rRNA sequencing analysis of mice feces showed that three types of dietary fiber exerted varying degrees of impact on the composition and abundance of gut microbiota while simultaneously promoting the biosynthesis of short-chain fatty acids. Specifically, HDF supplementation remarkably enhanced the abundance of Coprococcus, while HIDF and HSDF supplementation elevated the levels of Akkermansia and Allobaculum, respectively. Transcriptomic and proteomic results suggested the PPAR signaling pathway as a central regulatory mechanism influenced by these fibers. HDF and HIDF were particularly effective in modulating biological processes related to triglyceride and fatty acid metabolism, identifying Abcc3 and Dapk1 as potential targets. Conversely, HSDF primarily affected processes related to membrane lipids, ceramides, and phospholipids metabolism, with Pck1 identified as a potential target. Collectively, HDF, HIDF, and HSDF demonstrated distinct mechanisms in exerting exceptional anti-obesity properties. These insights may inform the development of personalized dietary interventions for obesity., 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.)

This study explored the differences in the in vitro fermentation properties of rice starch (RS) and rice starch-anthocyanins complexes (RS-A). Structural characterization suggested that RS and RS-A complexes showed a V-type crystalline structure. The degree of order (DO) and degree of double helix (DD) values of RS and RS-A complexes were enhanced after fermentation. Moreover, the RS-A complexes could improve the relative abundance of Bacteroidetes, Ruminococcaceae, and up-regulate gut microbiota diversity to maintain gut homeostasis. Relative abundance of potential metabolic pathways, such as energy metabolism, digestion system, and carbohydrate degradation overexpressed in the presence of RS-A complexes. The results demonstrated that the RS-A complexes had slower fermentation rates contributing to the transport of the formed short-chain fatty acid (SCFA) to the end of the colon and that the crystallinity might be a factor influencing the utilization of the starch matrix by the gut microbiota for SCFA formation., 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.)

Germination treatment of highland barley enhances its nutritional value while weakening the starch gel properties. This study aims to enhance the characteristics of germinated highland barley starch (GBS) by exploring the synergistic effects of two alkalis (Na 2 CO 3 and NaHCO 3 ) and guar gum (GG) on GBS gel properties. The combined action of alkalis and GG significantly improved the peak viscosity, setback viscosity, and hardness compared with GG alone. The highest G' and G" reached 998 and 204 Pa at 0.4% Na 2 CO 3 addition, which were increased by nearly 44% and 50%, respectively. Fourier-transform infrared spectral analysis revealed that the alkalis strengthened interaction forces, particularly with intensified absorption peaks at 3200-3700 cm -1 and 1550-1750 cm -1 . The Na 2 CO 3 and NaHCO 3 reduced the spin-spin relaxation time (T 2 ), resulting in a dense starch gel network. This study contributes to enhancing the market application of GBS and offers innovative insights for modifying other starches., 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.)

Pityriasis rubra pilaris (PRP) is an inflammatory papulosquamous dermatosis, characterized by hyperkeratotic follicular papules and erythematous desquamative plaques. The precise pathogenic mechanism underlying PRP remains incompletely understood. Herein, we conduct a case-control study involving a cohort of 102 patients with sporadic PRP and 800 healthy controls of Han Chinese population and identify significant associations (P = 1.73 × 10 -6 ) between PRP and heterozygous mutations in the Keratin 32 gene (KRT32). KRT32 is found to be predominantly localized in basal keratinocytes and exhibits an inhibitory effect on skin inflammation by antagonizing the NF-κB pathway. Mechanistically, KRT32 binds to NEMO, promoting excessive K48-linked polyubiquitination and NEMO degradation, which hinders IKK complex formation. Conversely, loss-of-function mutations in KRT32 among PRP patients result in NF-κB hyperactivation. Importantly, Krt32 knockout mice exhibit a PRP-like dermatitis phenotype, suggesting compromised anti-inflammatory function of keratinocytes in response to external pro-inflammatory stimuli. This study proposes a role for KRT32 in regulating inflammatory immune responses, with damaging variants in KRT32 being an important driver in PRP development. These findings offer insights into the regulation of skin immune homeostasis by keratin and open up the possibility of using KRT32 as a therapeutic target for PRP., (© 2024. The Author(s).)

Our previous studies have shown that sulfated Cyclocarya paliurus polysaccharides (SCP3) can alleviate intestinal oxidative stress (OS) damage by improving the antioxidant capacity of the intestine, but its mechanism still needs further exploration. This study aimed to reveal the possible underlying protective mechanism of SCP3 against OS damage of intestinal epithelial cells (IEC-6) based on transcriptome profiling. The results showed that SCP3 could increase the activity of superoxide dismutase and reduce the production of malondialdehyde and reactive oxygen species. In addition, the SCP3 could also alleviate the H 2 O 2 -induced high apoptosis rate and mitochondrial membrane potential decrease in IEC-6 cells. RNA-sequencing results showed that there were 2152 differentially expressed genes between the control group and the SCP3 group, and the mitogen-activated protein kinases (MAPK) and PI3K-Akt signaling pathways are the main signaling pathways that contributed to SCP3 protecting IEC-6 cells from OS damage. In summary, the SCP3 plays a role in improving intestinal cell damage by inhibiting OS, which may be closely related to the PI3K/Akt and MAPK signaling pathways. PRACTICAL APPLICATION: This study provides a theoretical basis for the practical application of Cyclocarya paliurus polysaccharides as an antioxidant ingredient in auxiliary medicines and functional foods., (© 2024 Institute of Food Technologists.)

The size or the curvature of nanoparticles (NPs) plays an important role in regulating the composition of the protein corona. However, the molecular mechanisms of how curvature affects the interaction of NPs with serum proteins still remain elusive. In this study, we employ all-atom molecular dynamics simulations to investigate the interactions between two typical serum proteins and PEGylated Au NPs with three different surface curvatures (0, 0.1, and 0.5 nm -1 , respectively). The results show that for proteins with a regular shape, the binding strength between the serum protein and Au NPs decreases with increasing curvature. For irregularly shaped proteins with noticeable grooves, the binding strength between the protein and Au NPs does not change obviously with increasing curvature in the cases of smaller curvature. However, as the curvature continues to increase, Au NPs may act as ligands firmly adsorbed in the protein grooves, significantly enhancing the binding strength. Overall, our findings suggest that the impact of NP curvature on protein adsorption may be nonmonotonic, which may provide useful guidelines for better design of functionalized NPs in biomedical applications.

Objective: To investigate the efficacy of sacubitril/valsartan in the treatment of peritoneal dialysis (PD) in patients with diabetes and heart failure with preserved ejection fraction (HFpEF)., Materials and Methods: Patients with diabetes who underwent PD and had HFpEF (n = 64) were divided into two groups: the experimental group (n = 31), which was administered sacubitril/valsartan, and the control group (n = 33), administered valsartan alone. Data were collected before and after treatment to compare the inter-group changes in cardiac function indexes, residual renal function (RRF), and PD adequacy indexes., Results: Compared with the control group, the N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were lower in the experimental group after treatment (Wilcoxon test, p < 0.05). The descent ranges of NT-proBNP, left ventricular end-systolic dimension, and left ventricular fraction shortening, as well as increases in the amplitude of left ventricular ejection fraction after treatment were better in the experimental group than in the control group (t-test, p < 0.05). The descent ranges of residual renal glomerular filtration rate, residual renal Kt/V urea , and residual renal creatinine clearance, as well as increases in the amplitude of β 2 -microglobulin, were lower in the experimental group than in the control group (Wilcoxon test, p < 0.05). However, there were no significant differences between the two groups in the descent ranges of the PD adequacy indexes (Wilcoxon test, p > 0.05). Hyperkalemia occurred in 8 cases (25.81%) in the experimental group and 13 cases (39.39%) in the control group, while hypotension occurred in 2 cases (6.45%) and 1 case (3.03%), respectively. No other adverse effects were observed in either group., Conclusion: The findings suggest that sacubitril/valsartan can safely and effectively improve RRF and cardiac function in patients with diabetes combined with HFpEF receiving PD, but it has little effect on PD adequacy.

Background: Crop diseases can lead to significant yield losses and food shortages if not promptly identified and managed by farmers. With the advancements in convolutional neural networks (CNN) and the widespread availability of smartphones, automated and accurate identification of crop diseases has become feasible. However, although previous studies have achieved high accuracy (>95%) under laboratory conditions (Lab) using mixed data sets of multiple crops, these models often falter when deployed under field conditions (Field). In this study, we aimed to evaluate disease identification accuracy under Lab, Field, and Mixed (Lab and Field) conditions using an assembled data set encompassing 14 diseases of apple (Malus × domestica Borkh.), potato (Solanum tuberosum L.), and tomato (Solanum lycopersicum L.). In addition, we investigated the impact of model architectures, parameter sizes, and crop-specific models (CSMs) on accuracy, using DenseNets, ResNets, MobileNetV3, EfficientNet, and VGG Nets., Results: Our results revealed a decrease in accuracy across all models from Lab (98.22%) to Mixed (91.76%) to Field (71.55%) conditions. Interestingly, disease classification accuracy showed minimal variation across model architectures and parameter sizes: Lab (97.61-98.76%), Mixed (90.76-92.31%), and Field (68.56-73.81%). Although CSMs were found to reduce inter-crop disease misclassifications, they also led to a slight increase in intra-crop misclassifications., Conclusion: Our findings underscore the importance of enriching data representation and volumes over employing new model architectures. Furthermore, the need for more field-specific images was highlighted. Ultimately, these insights contribute to the advancement of crop disease identification applications, facilitating their practical implementation in farmer's fields. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Water use efficiency (defined as the ratio of gross primary productivity to plant transpiration, WUE T ) describes the tradeoff between ecosystem carbon uptake and water loss. However, a comprehensive understanding of the impact of soil and atmospheric moisture deficits on WUE T across large regions remains incomplete. Solar-induced chlorophyll fluorescence (SIF) serves as an effective signal for measuring both terrestrial vegetation photosynthesis and transpiration, thereby enabling a rapid response to changes in the physiological status of plants under water stress. The objectives of this study were to: 1) mechanistically calculate WUE T using top-of-canopy SIF data and meteorological information by using the revised mechanistic light response model and the Penman-Monteith equation; 2) analyze the effects of atmospheric and soil water deficits on SIF-based WUE T by using decoupled soil water content (SWC) and vapor pressure deficit (VPD); 3) evaluate estimated SIF-based WUE T against data from 28 eddy covariance (EC) flux sites representing eight different vegetation types. Results indicated that the model performed well in ecosystems with dense canopies, explaining 56 % of the daily variability in EC tower-based WUE T . For the years 2019-2020, the global average WUE T derived from SIF was 3.49 g C/kg H 2 O. Notably, this value exceeded 4 g C/kg H 2 O in tropical rainforest regions near the equator and went beyond 5 g C/kg H 2 O in the high-latitude regions of the Northern Hemisphere. We found that SIF-based WUE T was primarily influenced by VPD rather than SWC in over 90 % of the global vegetated area. The model used in this study increased our ability to mechanistically estimate WUE T with SIF at the global scale, thereby highlighting the significance of the global response of SIF-based WUE T to water stress, and also enhancing our understanding of the water‑carbon cycle in terrestrial ecosystems., 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 AT-hook motif nuclear-localized ( AHL ) family is pivotal for the abiotic stress response in plants. However, the function of the cassava AHL genes has not been elucidated. Promoters, as important regulatory elements of gene expression, play a crucial role in stress resistance. In this study, the promoter of the cassava MeAHL31 gene was cloned. The MeAHL31 protein was localized to the cytoplasm and the nucleus. qRT-PCR analysis revealed that the MeAHL31 gene was expressed in almost all tissues tested, and the expression in tuber roots was 321.3 times higher than that in petioles. Promoter analysis showed that the MeAHL31 promoter contains drought, methyl jasmonate (MeJA), abscisic acid (ABA), and gibberellin (GA) cis -acting elements. Expression analysis indicated that the MeAHL31 gene is dramatically affected by treatments with salt, drought, MeJA, ABA, and GA3. Histochemical staining in the proMeAHL31-GUS transgenic Arabidopsis corroborated that the GUS staining was found in most tissues and organs, excluding seeds. Beta-glucuronidase (GUS) activity assays showed that the activities in the proMeAHL31-GUS transgenic Arabidopsis were enhanced by different concentrations of NaCl, mannitol (for simulating drought), and MeJA treatments. The integrated findings suggest that the MeAHL31 promoter responds to the abiotic stresses of salt and drought, and its activity is regulated by the MeJA hormone signal.

Background and Aim: Insomnia has been implicated in gastrointestinal diseases (GIs), but the causal effect between insomnia and GIs and underlying mechanisms remain unknown., Methods: By using the released summary-level data, we conducted a two-step Mendelian randomization (MR) analysis to examine the relationship between insomnia and four GIs and estimate the mediating role of candidate mediators. The first step was to investigate the causal association between insomnia and GIs using univariable MR analysis. The second step was to estimate the mediation proportion of selected mediators in these associations using multivariable MR analysis. Subsequently, results from different datasets were combined using the fixed-effect meta-analysis., Results: Univariable MR analysis provided strong evidence for the causal effects of insomnia on four GIs after Bonferroni correction for multiple comparisons, including peptic ulcer disease (PUD) (odds ratio [OR] = 1.15, 95% interval confidence [CI] = 1.10-1.20, P = 1.83 × 10 -9 ), gastroesophageal reflux (GORD) (OR = 1.19, 95% CI = 1.16-1.22, P = 5.95 × 10 -42 ), irritable bowel syndrome (IBS) (OR = 1.18, 95% CI = 1.15-1.22, P = 8.69 × 10 -25 ), and inflammatory bowel disease (IBD) (OR = 1.09, 95% CI = 1.03-1.05, P = 3.46 × 10 -3 ). In the mediation analysis, body mass index (BMI) and waist-to-hip ratio (WHR) were selected as mediators in the association between insomnia and PUD (BMI: mediation proportion [95% CI]: 13.61% [7.64%-20.70%]; WHR: 8.74% [5.50%-12.44%]) and GORD (BMI: 11.82% [5.94%-18.74%]; WHR: 7.68% [4.73%-11.12%])., Conclusions: Our findings suggest that genetically instrumented insomnia has causal effects on PUD, GORD, IBS, and IBD, respectively. Adiposity traits partially mediated the associations between insomnia and GIs. Further clinical studies are warranted to evaluate the protective effect of insomnia treatment on GIs., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Functional roles of SIGLEC15 in hepatocellular carcinoma (HCC) were not clear, which was recently found to be an immune inhibitor with similar structure of inhibitory B7 family members. SIGLEC15 expression in HCC was explored in public databases and further examined by PCR analysis. SIGLEC15 and PD-L1 expression patterns were examined in HCC samples through immunohistochemistry. SIGLEC15 expression was knocked-down or over-expressed in HCC cell lines, and CCK8 tests were used to examine cell proliferative ability in vitro. Influences of SIGLEC15 expression on tumor growth were examined in immune deficient and immunocompetent mice respectively. Co-culture system of HCC cell lines and Jurkat cells, flow cytometry analysis of tumor infiltrated immune cells and further sequencing analyses were performed to investigate how SIGLEC15 could affect T cells in vitro and in vivo. We found SIGLEC15 was increased in HCC tumor tissues and was negatively correlated with PD-L1 in HCC samples. In vitro and in vivo models demonstrated inhibition of SIGLEC15 did not directly influence tumor proliferation. However, SIGLEC15 could promoted HCC immune evasion in immune competent mouse models. Knock-out of Siglec15 could inhibit tumor growth and reinvigorate CD8+ T cell cytotoxicity. Anti-SIGLEC15 treatment could effectively inhibit tumor growth in mouse models with or without mononuclear phagocyte deletion. Bulk and single-cell RNA sequencing data of treated mouse tumors demonstrated SIGLEC15 could interfere CD8+ T cell viability and induce cell apoptosis. In all, SIGLEC15 was negatively correlated with PD-L1 in HCC and mainly promote HCC immune evasion through inhibition of CD8+ T cell viability and cytotoxicity., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Cyst excision and Roux-en-Y hepaticojejunostomy (RYHJ) is the standard treatment for choledochal cysts (CCs). In the present study, the results of totally laparoscopic surgery for CCs (TLCCs) in a pediatric population were evaluated. The clinical data of 28 children with CCs between June 2020 and June 2023 were retrospectively reviewed. All patients underwent TLCCs involving cyst excision and RYHJ. The jejunojejunal anastomosis was completed laparoscopically using manual sutures. Age at operation, operative time, postoperative recovery and complications were evaluated. The 28 patients comprised 8 boys and 20 girls who underwent TLCCs at a mean age of 4.2 years (range, 1 month-12.3 years) with a mean weight of 15.9 kg (range, 4.6-43 kg). All patients received ultrasound and magnetic resonance cholangiopancreatography examinations, which revealed a mean cyst diameter and length of 1.74±0.76 cm and 3.85±1.25 cm, respectively. The mean operative time was 214±43.8 min. The mean time until starting an oral diet after surgery was 2.89±1.23 days. Apart from bile leakage and wound infection, no other complications occurred during a median follow-up period of 18 months (range, 4-42 months). TLCCs can be performed safely by skilled surgeons in pediatric patients. TLCCs may be more physiologically compatible and accelerate recovery of intestinal function with reduced trauma and better esthetic outcomes than conventional laparoscopic surgery for CCs. Therefore, TLCCs with manual sutures may be considered as an option for minimally invasive surgery in pediatric patients with CCs., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2024, Spandidos Publications.)

Vectorial optical fields (VOFs) with extra degrees of freedom hold promise for many photonic applications. However, current methods to generate VOFs are either bulky in size or exhibit limited functionalities. Here, we demonstrate a tunable VOF generator by exciting plasmonic surface lattice resonances (SLRs) with axial symmetry. By meticulously arranging bilayer circular arrays with opposite handedness, we achieve a high Q-factor of 10 3 via just a few particles despite the general belief that too small array size suppresses the SLRs. This work presents tunable complex VOFs with distinct inhomogeneous spatial polarization distributions, which may enable various applications in integrated and polarization optics.

Household garbage rooms release abundant bioaerosols and are an important source of pathogens; however, information on the distribution and survival patterns of pathogens in different waste components is limited. In this study, a culture method and 16S rRNA high-throughput sequencing were used to determine bacterial communities, culturable pathogens, and human bacterial pathogens (HBPs). The results showed that abundant culturable bacteria were detected in all waste types, and a large number of S. aureus was detected on the surface of recyclable wastes, whereas S. aureus, total coliforms, Salmonella, Enterococcus, and hemolytic bacteria were detected in food waste and other waste. The activities of these detected pathogenic bacteria decreased after 24 h of storage but re-activated within one week. Factors affecting the emergence of pathogens varied with different waste components. Sequencing results showed that Pseudomonas, Acinetobacter, and Burkholderia were abundant in the waste samples, whereas Achromobacter, Exiguobacteriums, Bordetella, and Corynebacterium were the primary pathogens in the bioaerosol and wall attachment. The results of traceability analysis showed that bioaerosol microbes were mainly derived from raw kitchen waste (5.98%) and plastic and paper contaminated with food waste (19.93%) in garbage rooms. In addition, bioaerosols were the main source of microflora in the wall attachment, which possessed high HBP diversity and required more attention. These findings will help in understanding the microbial hazards in different waste components and provide guidance for the control and risk reduction of bioaerosols during waste management and recycling., 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.)

Both climate and impact models are essential for understanding and quantifying the impact of climate change on agricultural productivity. Multi-model ensembles have highlighted considerable uncertainties in these assessments, yet a systematic approach to quantify these uncertainties is lacking. We propose a standardized approach to attribute uncertainties in multi-model ensemble studies, based on insights from the Agricultural Model Intercomparison and Improvement Project. We find that crop model processes are the primary source of uncertainty in agricultural projections (over 50%), excluding unquantified hidden uncertainty that is not explicitly measured within the analyses. We propose multidimensional pathways to reduce uncertainty in climate change impact assessments., (© 2024. Springer Nature Limited.)

Superhydrophobic materials are attractive for industrial development but plagued by poor mechanical stability. Herein, a superdurable full-life superhydrophobic composite block is designed and fabricated by embedding near-zero contractive superhydrophobic silica aerogel into a rigid iron-nickel foam structured similarly to a regular dodecahedron. The synergistic protection afforded by these materials ensures superrobust mechanical stability for the composite block, which features a high compressive strength of up to ≈7.4 MPa, and ultralow Taber abrasion of down to ≈0.567 mm after withstanding 50 000 cycles, and highly efficient water harvesting capability of up to ≈3114.3 mg min -1 cm -2 at a supercooling degree of 40 K. This robust material system provides a novel strategy to design superhydrophobic materials capable of withstanding extreme conditions, including high temperature, humidity, pressure, and abrasion., (© 2024 Wiley‐VCH GmbH.)

In the study, a sweet wine koji (YQ-5) was successfully selected to make frozen Chinese sweet rice wine dough (F-CD) for flavor enrichment. Subsequently, the effects of single improver (SI: xanthan gum, potassium carbonate, antifreeze protein, diacetyl tartaric esters of monoglycerides and composite improver (XPADG: Four improvers mixed in proportion) on the texture, rheological properties, microstructure, water status, protein secondary structure, volatile flavor substances and sensory properties of F-CD during frozen storage were investigated. The results indicated that XPADG slowed the increase in freezable water and water mobility in the dough, giving dough the most stable rheological properties and minimizing the damage of freezing to the secondary structure and microstructure of proteins. Besides, GC-QTOF/MS analysis showed that XPADG may facilitate the retention of flavoring substances in F-CD after storage for 6 days. Finally, the sensory evaluation showed that XPADG imparted good sensory properties to the product after freezing for 6 days., 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 & Aims: The effectiveness of immune checkpoint inhibitor (ICI) therapy for hepatocellular carcinoma (HCC) is limited by treatment resistance. However, the mechanisms underlying immunotherapy resistance remain elusive. We aimed to identify the role of CT10 regulator of kinase-like (CRKL) in resistance to anti-PD-1 therapy in HCC., Methods: Gene expression in HCC specimens from 10 patients receiving anti-PD-1 therapy was identified by RNA-sequencing. A total of 404 HCC samples from tissue microarrays were analyzed by immunohistochemistry. Transgenic mice (Alb-Cre/Trp53 fl/fl ) received hydrodynamic tail vein injections of a CRKL-overexpressing vector. Mass cytometry by time of flight was used to profile the proportion and status of different immune cell lineages in the mouse tumor tissues., Results: CRKL was identified as a candidate anti-PD-1-resistance gene using a pooled genetic screen. CRKL overexpression nullifies anti-PD-1 treatment efficacy by mobilizing tumor-associated neutrophils (TANs), which block the infiltration and function of CD8 + T cells. PD-L1 + TANs were found to be an essential subset of TANs that were regulated by CRKL expression and display an immunosuppressive phenotype. Mechanistically, CRKL inhibits APC (adenomatous polyposis coli)-mediated proteasomal degradation of β-catenin by competitively decreasing Axin1 binding, and thus promotes VEGFα and CXCL1 expression. Using human HCC samples, we verified the positive correlations of CRKL/β-catenin/VEGFα and CXCL1. Targeting CRKL using CRISPR-Cas9 gene editing (CRKL knockout) or its downstream regulators effectively restored the efficacy of anti-PD-1 therapy in an orthotopic mouse model and a patient-derived organotypic tumor spheroid model., Conclusions: Activation of the CRKL/β-catenin/VEGFα and CXCL1 axis is a critical obstacle to successful anti-PD-1 therapy. Therefore, CRKL inhibitors combined with anti-PD-1 could be useful for the treatment of HCC., Impact and Implications: Here, we found that CRKL was overexpressed in anti-PD-1-resistant hepatocellular carcinoma (HCC) and that CRKL upregulation promotes anti-PD-1 resistance in HCC. We identified that upregulation of the CRKL/β-catenin/VEGFα and CXCL1 axis contributes to anti-PD-1 tolerance by promoting infiltration of tumor-associated neutrophils. These findings support the strategy of bevacizumab-based immune checkpoint inhibitor combination therapy, and CRKL inhibitors combined with anti-PD-1 therapy may be developed for the treatment of HCC., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Loss-of-function mutations in CREBBP, which encodes for a histone acetyltransferase, occur frequently in B-cell malignancies, highlighting CREBBP deficiency as an attractive therapeutic target. Using established isogenic cell models, we demonstrated that CREBBP-deficient cells are selectively vulnerable to AURKA inhibition. Mechanistically, we found that co-targeting CREBBP and AURKA suppressed MYC transcriptionally and post-translationally to induce replication stress and apoptosis. Inhibition of AURKA dramatically decreased MYC protein level in CREBBP-deficient cells, implying a dependency on AURKA to sustain MYC stability. Furthermore, in vivo studies showed that pharmacological inhibition of AURKA was efficacious in delaying tumor progression in CREBBP-deficient cells and was synergistic with CREBBP inhibitors in CREBBP-proficient cells. Our study sheds light on a novel synthetic lethal interaction between CREBBP and AURKA, indicating that targeting AURKA represents a potential therapeutic strategy for high-risk B-cell malignancies harboring CREBBP inactivating mutations., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

An antioxidant amyloid fibril was prepared as an emulsifier by fibrillating limited enzymatic hydrolysis-modified rice protein (HRP). The purpose of this study was to investigate the feasibility of using fibrillated HRP to stabilize oil-in-water emulsion. A free radical scavenging assay revealed that the antioxidant activity of fibrillated HRP was 2.09 times higher than that of native rice protein. Fibrillated HRP demonstrated a marked reduction in interfacial tension, increased surface hydrophobicity and contact angle (> 80°), and rapid adsorption to the interface, with 35.34 ± 2.43% interfacial adsorbed protein content. The fibrillated HRP barriers resisted environment stresses such as NaCl, pH variations, long-term storage, while reducing lipid oxidation degree. Additionally, fibrillated HRP-based emulsion was more effective in protecting β-carotene from degradation compared to other samples. These findings provide theoretical support for the development of rice protein-based antioxidant emulsifiers and modification of emulsifying properties of plant proteins., 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.)

Considering the high abundance of bound polyphenols (BP) in whole grain dietary fiber (DF), this study utilized multi-omics approach to evaluate the impact of BP of defatted rice bran insoluble DF (RIDF) in modulating obesity. Mice on high-fat diet were gavage-administered RIDF, BP-removed or formulated RIDF. The results indicated that DF significantly reduced serum total cholesterol, triglycerides, high-density and low-density lipoprotein cholesterol levels. Moreover, hepatic lipid accumulation and damage induced by high-fat diet were significantly ameliorated with DF intervention. The presence of BP increased the abundance of beneficial bacteria g&#95;Akkermansia and g&#95;Butyricicocus, as well as the expression of butyric acid/propionic acid. Furthermore, the expression of hepatic lipids and lipid-like molecules was significantly decreased under the combined intervention of BP and DF, and this was accompanied by alterations in genes related to lipid, sterol, and cholesterol metabolic biological processes. These findings suggest that BP contribute to the anti-obesity effects of DF., 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.)

Global warming has led to severe land desertification on the Mongolian plateau. It puts great environmental pressure on vegetation communities. This pressure leads to fragmentation of land use and landscape patterns, thus triggering changes in the spatial distribution patterns of vegetation. The spatial distribution pattern of vegetation is crucial for the performance of its ecosystem services. However, there is not enough research on the relationship between large-scale spatial distribution patterns of vegetation and ecosystem services. Therefore, this study is to construct an ecological spatial network on the Mongolian Plateau based on landscape ecology and complex network theory. Combining pattern analysis methods to analyze the network, we obtained the spatial and temporal trends of forest and grass spatial distribution patterns from 2000 to 2100, and explored the relationship between the topological properties of source patches and ecosystem services in different patterns. It was found that there are four basic patterns of spatial distribution of forest and grass in the Mongolian Plateau. The Core-Linked Ring pattern accounts for 40.74 % and exhibits the highest stability. Under the SSP5-RCP8.5 scenario, source patches are reduced by 22.76 % in 2100. Topological indicators of source patches showed significant correlations with ecosystem services. For example, the CUE of grassland patches in the Centralized Star pattern was positively correlated with betweeness centrality. The most significant improvement in WUE after optimization is 19.90 % compared to pre-optimization. The conclusion of the study shows that the spatial distribution pattern of vegetation can be used to enhance the stability of ecological spatial network and improve ecosystem services at a larger scale. It can provide a certain reference for the study of spatial patterns of vegetation distribution in arid and semi-arid areas., 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.)

The deep marine sediments represent a major repository of organic matter whilst hosting a great number of uncultivated microbes. Microbial metabolism plays a key role in the recycling of organic matter in the deep marine sediments. D-amino acids (DAAs) and DAA-containing muropeptides, an important group of organic matter in the deep marine sediments, are primarily derived from bacterial peptidoglycan decomposition. Archaea are abundant in the deep ocean microbiome, yet their role in DAA metabolism remains poorly studied. Here, we report bioinformatic investigation and enzymatic characterization of deep marine sedimentary archaea involved in DAA metabolism. Our analyses suggest that a variety of archaea, particularly the Candidatus Bathyarchaeota and the Candidatus Lokiarchaeaota, can metabolize DAAs. DAAs are converted into L-amino acids via amino acid racemases (Ala racemase, Asp racemase and broad substrate specificity amino acid racemase), and converted into α-keto acid via d-serine ammonia-lyase, whereas DAA-containing di-/tri-muropeptides can be hydrolyzed by peptidases (dipeptidase and D-aminopeptidase). Overall, this study reveals the identity and activity of deep marine sedimentary archaea involved in DAA metabolism, shedding light on the mineralization and biogeochemical cycling of DAAs in the deep marine sediments., 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 use of observation-dependent methods for crop productivity and food security assessment is challenging in data-sparse regions. This study presents a transferable framework and applies it to North Korea (NK) to assess rice productivity based on climate similarity, transferable machine-learning techniques, and extendable multi-source data. We initially divided the primary phenological stages of rice in the study region and extracted dynamic rice distributions based on Moderate Resolution Imaging Spectroradiometer products and phenological observations. We compared the performances of four representative environmentally driven models (Linear Regression, back-propagation Neural Network, Support Vector Machine, and Random Forest) in simulating rice productivity using an extensive dataset that included multi-angle vegetation monitoring, climate variables, and planting distribution information. The framework integrated an optimal environmentally driven model with agricultural management practices for transferability to predict rice productivity in NK over multiple years. Additionally, two crop growth scenarios (whole growth period (WGP) and seeding-heading period (SHP)) were compared to assess pre-harvest forecasting capabilities and identify dominant factors. Finally, independent datasets from the Food and Agriculture Organization, World Food Program, and Global Gridded Crop Models were used to validate the magnitude and spatial distribution of the predicted results. The results showed that phenological identification based on remote sensing can accurately capture rice growth characteristics and map rice distribution. Random Forest outperformed other models in simulating rice productivity variation, with r-squares of 0.87 and 0.83 in the WGP and SHP, respectively. The solar-induced chlorophyll fluorescence, maximum temperature, and evapotranspiration collectively determined approximately 40 % of the variation in yield simulated using Random Forest. Conversely, planting areas contributed over 42 % of the variation in rice production. Compared to Food and Agriculture Organization statistics, the environmentally driven framework explained 78.72 % and 76.89 % of the production variation and 69.42 % and 71.15 % of the yield variation in NK under the WGP and SHP, respectively. Moreover, the environmental management-driven framework captured over 90 % of the yield variation. The predicted spatial pattern of rice productivity exhibited significant concordance with the World Food Program and Global Gridded Crop Model reports. In summary, the proposed transferable framework for crop productivity assessment contributes to early warnings of production reduction and has the potential for scalability across various crops and data-sparse regions., 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.)

Marine bacterial proteases have rarely been used to produce bioactive peptides, although many have been reported. This study aims to evaluate the potential of the marine bacterial metalloprotease A69 from recombinant Bacillus subtilis in the preparation of peanut peptides (PPs) with antioxidant activity and angiotensin-converting enzyme (ACE)-inhibitory activity. Based on the optimization of the hydrolysis parameters of protease A69, a process for PPs preparation was set up in which the peanut protein was hydrolyzed by A69 at 3000 U g -1 and 60 °C, pH 7.0 for 4 h. The prepared PPs exhibited a high content of peptides with molecular weights lower than 1000 Da (>80%) and 3000 Da (>95%) and contained 17 kinds of amino acids. Moreover, the PPs displayed elevated scavenging of hydroxyl radical and 1,1-diphenyl-2-picryl-hydrazyl radical, with IC 50 values of 1.50 mg mL -1 and 1.66 mg mL -1 , respectively, indicating the good antioxidant activity of the PPs. The PPs also showed remarkable ACE-inhibitory activity, with an IC 50 value of 0.71 mg mL -1 . By liquid chromatography mass spectrometry analysis, the sequences of 19 ACE inhibitory peptides and 15 antioxidant peptides were identified from the PPs. These results indicate that the prepared PPs have a good nutritional value, as well as good antioxidant and antihypertensive effects, and that the marine bacterial metalloprotease A69 has promising potential in relation to the preparation of bioactive peptides from peanut protein.

Antibiotics in water will cause serious harm to human health and ecosystem. Carbon-based materials and transition metals activated peroxodisulfate (PDS) to produce active species, which can degrade residual antibiotics in water. In this paper, Cu/CNF (carbon nanofibers) composites were first prepared by introducing Cu into CNF using electrostatic spinning technology, which was used to activate PDS to degrade tetracycline (TC). The degradation efficiency of Cu/CNF/PDS was 36.23% higher than that of CNF/PDS. The reason is that introducing Cu can increase the number of surface functional groups and specific surface area of CNF, and then improve the catalytic performance. The functional groups and Cu species are the active sites for catalytic PDS. Moreover, the main ways to degrade TC in the Cu/CNF/PDS system are singlet oxygen ( 1 O 2 ) and electron transfer. Based on the above analysis, we modified CNF with transition metal salts, prepared efficient environmental functional materials, and used them for PDS activation, providing a theoretical basis and technical support for the degradation of antibiotic pollutants and creating new ideas for other research.

This study aimed to investigate the mitigation effect of epigallocatechin gallate (EGCG) on aging induced by 3-monochloropropane-1,2-diol (3-MCPD) in Caenorhabditis elegans , evaluate health indicators during the process, and reveal the underlying mechanism through transcriptomics and identification of mutants. The results showed that EGCG alleviated the declined fertility, shortened lifespan, reduced body size, weakened movement, increased reactive oxygen species and lipofuscin, and damaged antioxidative stress response and excessive heat shock proteins caused by 3-MCPD. Transcriptomics study indicated that treatment with 3-MCPD and EGCG altered gene expression, and gene mutants confirmed the involvement of insulin/IGF-1 signaling pathway in mediating the process that EGCG alleviated the aging toxicity induced by 3-MCPD. The study showed that EGCG alleviated the aging toxicity induced by 3-MCPD.

Ischemic stroke (IS) is one of the main causes inducing death and disability in adults. Because of the high recurrence rate of IS, prevention of recurrence is of great significance to this population, for which the evidence-based and effective secondary prevention strategy is an important means, and acupuncture intervention has a positive effect on its risk factors. In the present article, we reviewed the progress of researches on the mechanisms of acupuncture underlying prevention of IS relapse from the perspective of its main risk factors, namely 1) hypertension (preventing and controlling the adverse effects caused by the imbalance of blood pressure level, vascular and other tissue structures, endocrine factors and central nervous system activities in patients with hypertension after IS), 2) hypercholesterolemia (lowering serum total cholesterol, triglyceride, low-density lipoprotein-cholesterol (LDL-C) and raising high-density lipoprotein cholesterol), 3) diabetes (regulating the secretion function of adipose tissue, activating the insulin signal transduction pathway, protecting the function of pancreatic β cells, and regulating the central nervous system functions to participate in the secondary prevention of IS), 4) smoking (relieving the symptoms of smoking cessation and reducing the smoker's dependence on smoking by changing the internal environment, lowering the level of blood endorphin and regulating the excitability of central nervous system), 5) sleep apnea syndrome (regulating local muscle function and the excitability of the nervous system, but also affecting some organic changes as reducing tonsil swelling) and 6) obesity (lowering blood glucose and lipid, increasing the ratio of brown/white fat, reducing leptin resistance, and suppressing appetite to induce body weight loss, or directly regulate the changes of fat tissue, etc). Results shows that the acupuncture's regulatory mechanism for IS risk factors is closely related to the neuroendocrine system, and simultaneously involves multiple targets of multiple risk factors. Due to its good efficacy and safety, acupuncture therapy is of great value for clinical promotion as an important intervention for secondary prevention.

An ammonium ylide-based relay annulation was disclosed, which uses DABCO as the catalyst and oxindole-derived α,β-unsaturated ketimines and γ-bromo-crotonates as the starting materials. This method enables the rapid assembly of a series of structurally novel spiro-polycyclic oxindoles containing a bicyclo[4.1.0]heptane moiety through simultaneous generation of three new bonds and two rings in one step under mild reaction conditions.

Background: Innate/adaptive immunity is the key to anti-tumor therapy. However, its causal relationship to Gastrointestinal (GI) cancer remains unclear., Methods: Immunity genes were extracted from the MSigDB database. The Genome-wide association studies (GWAS) summary data of GI cancer were integrated with expression quantitative trait loci (eQTL) and DNA methylation quantitative trait loci (mQTL) associated with genes. Summary-data-based Mendelian randomization (SMR) and co-localization analysis were used to reveal causal relationships between genes and GI cancer. Two-sample MR analysis was used for sensitivity analysis. Single cell analysis clarified the enrichment of genes., Results: Three-step SMR analysis showed that a putative mechanism, cg17294865 CpG site regulating HLA-DRA expression was negatively associated with gastric cancer risk. HLA-DRA was significantly differentially expressed in monocyte/macrophage and myeloid cells in gastric cancer., Conclusion: This study provides evidence that upregulating the expression level of HLA-DRA can reduce the risk of gastric cancer., (© 2024. The Author(s).)

Non-volatile magnetic random-access memories have proposed the need for spin channel switching. However, this presents a challenge as each spin channel reacts differently to the external field. Tellurene is a semiconductor with a tunable bandgap, excellent stability, and high carrier concentration, but its lack of magnetic properties has hindered its application in spintronics. In this work, the influence of an external field on transition metal (TM)-doped β-tellurene is systematically analysed from first principles. First, the active-learning moment-tensor-potential (MTP) is used to verify the thermal stability of the V-doped system with the MTP proving to be 900 times faster than the traditional method. Subsequently, under biaxial strain ranging from -2% to 10%, the V-doped system undergoes a gradual transition from a magnetic semiconductor to a spin-gapless semiconductor, and further to a half-metal and magnetic metal. The band structure can be maintained under an electric field. By examining the magnetic anisotropy energy, the lattice changes profoundly impact the electromagnetic properties, particularly with the TMs being sensitive to strain. Moreover, the band structure is reflected in the spin resolution current of the magnetic tunnel junction. This work investigates the response of doped β-Te to external fields, revealing its potential applications in spintronics.

Loss of ferroptosis contributes to the development of human cancer, and restoration of ferroptosis has been demonstrated as a potential therapeutic strategy in cancer treatment. However, the mechanisms of how ferroptosis escape contributes to ovarian cancer (OV) development are not well elucidated. Here, we show that ferroptosis negative regulation signatures correlated with the tumorigenesis of OV and were associated with poor prognosis, suggesting that restoration of ferroptosis represents a potential therapeutic strategy in OV. High-throughput drug screening with a kinase inhibitor library identified MEK inhibitors as ferroptosis inducers in OV cells. We further demonstrated that MEK inhibitor-resistant OV cells were less vulnerable to trametinib-induced ferroptosis. Mechanistically, mTOR/eIF4E binding protein 1 (4EBP1) signaling promoted solute carrier family 7 member 11 (SLC7A11) protein synthesis, leading to ferroptosis inhibition in MEK inhibitor-resistant cells. Dual inhibition of MEK and mTOR/4EBP1 signaling restrained the protein synthesis of SLC7A11 via suppression of the mTOR/4EBP1 axis to reactivate ferroptosis in resistant cells. Together, these findings provide a promising therapeutic option for OV treatment through ferroptosis restoration by the combined inhibition of MEK and mTOR/4EBP1 pathways.

Background: Chronic total coronary occlusion (CTO) is an extremely hazardous condition that leads to various clinical phenomena and complications and results in social and economic burdens. Hyperuricemia (HU) is often associated with atherosclerosis. Few studies, however, have investigated the risk of CTO in individuals with HU and the role of traditional cardiovascular risk factors in this setting., Methods: A cohort of 1245 individuals without chronic kidney disease from southwest China who underwent coronary angiography between February 2018 and June 2021 were enrolled. CTO was defined as a total occlusion of any coronary artery or arteries for more than 3 months. HU was defined as a serum uric acid level of ≥420 µmol/L in men and ≥360 µmol/L in women. Univariate and multivariate logistic regression models and subgroup analyses were applied to assess the relationship between HU and CTO., Results: After adjustment, HU was noted to be associated with a 1.47-fold increase in the risk of CTO [odds ratio (OR), 1.47; 95% confidence interval (CI), 1.06-2.58; P = 0.026]. As a continuous variable, uric acid was an independent predictor of CTO (OR, 1.002; 95% CI, 1.001-1.004; P = 0.047). Subgroup analyses showed that the risk of CTO was higher among individuals under 65 years of age (OR, 2.77; 95% CI, 1.3-5.89), nonobese individuals (OR, 1.9; 95% CI, 1.16-3.1), and those with dyslipidemia (OR, 1.8; 95% CI, 1.04-3.11), while sex, smoking, hypertension, and diabetes did not show similar effects. Interaction analyses revealed no interaction among subgroups., Conclusion: Among individuals residing in southwest China, HU was associated with an increased risk of CTO in non-CKD individuals, especially those under 65 years of age and nonobese and dyslipidemic individuals., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)