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In recent decades, global aquaculture has expanded rapidly, raising concerns about coastal environmental degradation due to unregulated or poorly regulated discharge of aquaculture tailwater. Despite the crucial role of dissolved organic matter (DOM) in biogeochemical processes and aquatic biodiversity, the influence of aquaculture type on the molecular characteristics of DOM remains largely unexplored. Herein, this study investigated the variations in chemical and spectroscopic properties as well as molecular characteristics and composition of DOM across different aquaculture types including crustacean, fish and shellfish. Our findings revealed notable differences in DOM quantities among different aquaculture types, with crustacean and fish aquaculture water containing higher DOM amount compared to shellfish aquaculture water. This disparity can be attributed to the more frequent formulated feeds of crustacean and fish in contrast to shellfish aquaculture. Furthermore, distinct differences were also observed in the characteristics and composition of DOM among the different aquaculture waters. Specifically, DOM in shellfish aquaculture water exhibited a higher abundance of unsaturated and reduced molecules as well as increased aromaticity compared to the other two aquaculture waters. Conversely, DOM from fish aquaculture water showed a greater contribution from terrestrial origin characterized by elevated levels of plant-based components such as lignin-like and tannin-like compounds. Interestingly, DOM from shellfish aquaculture water contained lower levels of microbial-derived components such as lipid-like and protein-like compounds, likely due to reduced microorganism populations resulting from lower nutrients availability and higher salinity. Overall, these significant variations in characteristics and composition of DOM underscore the potential impacts of aquaculture type on the DOM biogeochemical cycle and the environmental quality in aquatic 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 Elsevier Ltd. All rights reserved.)

Background: Pea protein isolate (PPI) is gaining increasing popularity in the food industry. It provides a diverse range of health benefits, such as hypoallergenic and gluten-free characteristics. However, the functional performance of PPI is hindered by its low solubility and poor stability. Therefore, in this article, PPI and dextran (DX) of different molecular weights were grafted to investigate the effects of grafting DX with different molecular weights on the interface properties and antioxidant properties of PPI. Additionally, the stability and digestive properties of the glycated PPI nanoemulsion system were explored., Results: The result showed that the grafting degree of PPI-DX conjugates (PPI-DC) decreased with an increase in the molecular weight of DX. Surface hydrophobicity, antioxidant activity and solubility of PPI-DC were significantly improved after grafting compared with PPI and PPI-DX mixtures (PPI-DM). Astaxanthin-loaded emulsions stabilized by grafted conjugates had smaller droplets and higher astaxanthin encapsulation rate compared to PPI emulsions. In vitro digestion demonstrated that the bioavailability of PPI-DC emulsions was higher than of PPI emulsion. Furthermore, after 24 days of storage, retention rate of astaxanthin-loaded emulsions prepared by conjugates remained above 70%, surpassing that of PPI emulsion., Conclusion: These results indicated that DX grafting can improve the emulsion properties of PPI. In addition, the DX with a molecular weight of 5 kDa showed the most significant improvement. This study contributes to the advancement of natural emulsifiers by modifying PPI through glycation, and furnishes a valuable reference for its utilization in functional foods. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Palbociclib, a selective CDK4/6 inhibitor with potent anti-tumor effects, was investigated for its interaction with human α1-acid glycoprotein (HAG). Spectral analysis revealed that palbociclib forms a ground state complex with HAG, exhibiting binding constant (K b ) of 10 4  M -1 at the used temperature range. The interaction between the two was determined to be driven mainly by hydrogen bonding and hydrophobic forces. Multispectral studies indicated that the bound palbociclib altered the secondary structure of HAG and reduced polarity around Trp and Tyr amino acids. And, molecular docking and dynamics simulations verified the experimental findings. Finally, most of the metal ions present in plasma, such as K + , Cu 2+ , Ca 2+ , Mg 2+ , Ni 2+ , Fe 3+ , and Co 2+ , are detrimental to the binding of palbociclib to HAG, with the exception of Zn 2+ , which is favorable., 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.)

Ternary copper indium sulfide (CIS) quantum dots (QDs) have been emerging as attractive alternatives to Cd- and Pb-based QDs in various applications owing to their favorable optical properties and low toxicity. However, methods allowing continuous production of CIS QDs in an easy-to-perform and/or organic-solvent-free way are yet to be realized. Here, we report a facile, rapid, continuous, and aqueous synthetic approach for CIS QDs based on a microwave-assisted microfluidic (MAM) technique with easy scale-up of production. Typically, CIS QDs and CIS@ZnS QDs are continuously produced with a flow rate of 30 mL h -1 at a moderate temperature (∼95 °C) in an open-air system with a continuous flow of water as the reaction medium. This continuous synthesis process circumvents the requirements of batch operation, a degassed/inert atmosphere, high temperatures, organic solvents, and complex/expensive equipment. The resulting water-soluble CIS@ZnS QDs show a photoluminescence quantum yield of 44%. This work provides an efficient and green synthetic route for the scalable production of fluorescent nanomaterials.

The study aimed to describe the prevalence of lymph node metastases per lymph node station for esophageal squamous cell carcinoma (ESCC) after neoadjuvant treatment. Clinicopathological variables of ESCC patients were retrieved from the prospective database of the Surgical Esophageal Cancer Patient Registry in West China Hospital, Sichuan University. A two-field lymphadenectomy was routinely performed, and an extensive three-field lymphadenectomy was performed if cervical lymph node metastasis was suspected. According to AJCC/UICC 8, lymph node stations were investigated separately. The number of patients with metastatic lymph nodes divided by those who underwent lymph node dissection at that station was used to define the percentage of patients with lymph node metastases. Data are also separately analyzed according to the pathological response of the primary tumor, neoadjuvant treatment regimens, pretreatment tumor length, and tumor location. Between January 2019 and March 2023, 623 patients who underwent neoadjuvant therapy followed by transthoracic esophagectomy were enrolled. Lymph node metastases were found in 212 patients (34.0%) and most frequently seen in lymph nodes along the right recurrent nerve (10.1%, 58/575), paracardial station (11.4%, 67/587), and lymph nodes along the left gastric artery (10.9%, 65/597). For patients with pretreatment tumor length of >4 cm and non-pathological complete response of the primary tumor, the metastatic rate of the right lower cervical paratracheal lymph nodes is 10.9% (10/92) and 10.6% (11/104), respectively. For patients with an upper thoracic tumor, metastatic lymph nodes were most frequently seen along the right recurrent nerve (14.2%, 8/56). For patients with a middle thoracic tumor, metastatic lymph nodes were most commonly seen in the right lower cervical paratracheal lymph nodes (10.3%, 8/78), paracardial lymph nodes (10.2%, 29/285), and lymph nodes along the left gastric artery (10.4%, 30/289). For patients with a lower thoracic tumor, metastatic lymph nodes were most frequently seen in the paracardial station (14.2%, 35/247) and lymph nodes along the left gastric artery (13.1%, 33/252). The study precisely determined the distribution of lymph node metastases in ESCC after neoadjuvant treatment, which may help to optimize the extent of lymphadenectomy in the surgical management of ESCC patients after neoadjuvant therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Spinal cord injury (SCI) is a serious neurological injury that is currently extremely difficult to cure clinically. SCI involves numerous pathophysiological processes, and microRNAs (miRNAs) play an important role in these processes. Meanwhile, miRNAs have received a lot of attention for their role in other diseases as well. Therefore, the detection of disease-related miRNAs is important for the study of disease development, treatment, and prognosis. With the rapid development of molecular biology, the traditional detection methods of miRNA can no longer meet the needs of experiments. Electrochemical detection methods are widely used because of their excellent detection performance. Here, we designed an electrochemical sensor prepared using borosilicate glass microneedle electrodes for real-time monitoring of miR-21-5p expression in vivo after SCI. The sensor showed a good linear relationship between the oxidation peak current value and the concentration of miR-21-5p in the concentration range 0-2 fM ( Y = 12.025 X + 90.396, R 2 = 0.98). The limit of detection (LOD) of the sensor was 0.3667 fM. The experimental results showed that the borosilicate glass microneedle electrochemical sensor achieved fast, accurate, highly sensitive, highly specific, highly stable, and reproducible monitoring of miR-21-5p. More importantly, the electrochemical sensor has a better clinical translation prospect, which is important for the research of clinical diseases.

Small-scale systems based on periodic boundary conditions often cannot accurately describe real-world situations, especially when conducting molecular dynamics simulations to study phase transitions, where it is very necessary to use large-scale systems. However, studying phase transitions in large-scale systems is an important and difficult task. Though ab initio molecular dynamics (AIMD), based on density functional theory (DFT), provides advantages in terms of accuracy, it is very difficult to study phase transitions in large-scale systems due to the considerable computational time required. In addition, although traditional empirical potentials are faster, their lower calculation accuracy makes it difficult to use them for phase transition studies. It is crucial to devise a method that has enabled a promising fusion of computational efficiency and precision to effectively investigate phase transitions in large-scale systems. In this work, the obtained machine learning potential function of carbon through deep neural networks not only demonstrates strong scalability but also effectively enables the study of the formation mechanisms of amorphous diamond and polycrystalline diamond using C 60 crystals and graphene as precursors under high-pressure high-temperature conditions (HPHT). Furthermore, the structure search software (AIRSS) was used to generate numerous initial structures which were optimized using the machine learning potential, a process which led to finding new structural clusters of carbon. Interestingly, the predictive capabilities of the machine learning potential for symmetric and asymmetric carbon clusters aligned well with the Gaussian approximation potential (GAP), yet the former demonstrated higher computational efficiency, making it more suitable for carbon material research. The results of this work signify significant progress in the field of carbon transition study, opening up new possibilities for exploring and understanding carbon materials with improved computational efficacy.

The red imported fire ant Solenopsis invicta Buren (Hymenoptera: Formicidae) is native to South America; however, its introduction to other countries has caused serious biodiversity, agricultural, and public health problems. As toxic bait is an effective method to control fire ant populations, the aim of this study was to determine the most effective concentration of sulfoxaflor, flupyradifurone, and triflumezopyrim as ingredients for baits against S. invicta under laboratory and field conditions. Sulfoxaflor, flupyradifurone, and triflumezopyrim had no effect on the feeding behavior of the fire ants. However, they significantly reduced the climbing, walking, and arrest abilities of the fire ant workers after 10 days of treatment, and insecticides were horizontally transferred from workers to alates or larvae. Specifically, sulfoxaflor and triflumezopyrim at 0.05% concentration were the most effective in exterminating fire ants. Sulfoxaflor and triflumezopyrim are nonrepellent and effective insecticides against S. invicta .

Soybean domestication has significantly changed key agronomic traits, yet its impact on leaf photosynthetic phosphorus-use efficiency (PPUE) and its underlying traits remain poorly known. Further information on this would be important to increase soybean P-use efficiency. To address this gap, 48 soybean accessions (16 wild relatives, 16 landraces and 16 cultivars) were used to compare leaf anatomical traits, foliar chemical P fractions, P allocation and PPUE under two P levels. The results showed that the cultivars had higher area-based and mass-based photosynthesis rates, PPUE, metabolite P concentration, and its percentage of leaf total P, as well as a greater percentage of lipid P, nucleic acid P and residual P. Conversely, wild relatives tended to have higher leaf P concentration, palisade:spongy thickness ratio, and concentrations of inorganic P, nucleic acid P, lipid P and residual P. PPUE was negatively correlated with leaf inorganic P concentration and its percentage relative to leaf total P, while it was positively correlated with the concentration and percentage of metabolite P. We concluded that soybean domestication increased PPUE, as a result of both increased photosynthesis rate and decreased leaf P concentration; domestication reduced the palisade:spongy thickness ratio coupled with increased allocation of P to P-containing metabolites, thereby contributing to faster photosynthesis and higher PPUE. This study shed light on the significance of leaf P allocation and anatomical traits affecting PPUE during soybean domestication, offering a mechanistic understanding to further enhance soybean P-use efficiency., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Sex pheromones, which consist of multiple components in specific ratios promote intraspecific sexual communications of insects. Plutella xylostella (L.) is a worldwide pest of cruciferous vegetables, the mating behavior of which is highly dependent on its olfactory system. Long trichoid sensilla on male antennae are the main olfactory sensilla that can sense sex pheromones. However, the underlying mechanisms remain unclear. In this study, 3 sex pheromone components from sex pheromone gland secretions of P. xylostella female adults were identified as Z11-16:Ald, Z11-16:Ac, and Z11-16:OH in a ratio of 9.4 : 100 : 17 using gas chromatography - mass spectrometry and gas chromatography with electroantennographic detection. Electrophysiological responses of 581 and 385 long trichoid sensilla of male adults and female adults, respectively, to the 3 components were measured by single sensillum recording. Hierarchical clustering analysis showed that the long trichoid sensilla were of 6 different types. In the male antennae, 52.32%, 5.51%, and 1.89% of the sensilla responded to Z11-16:Ald, Z11-16:Ac, and Z11-16:OH, which are named as A type, B type, and C type sensilla, respectively; 2.93% named as D type sensilla responded to both Z11-16:Ald and Z11-16:Ac, and 0.34% named as E type sensilla were sensitive to both Z11-16:Ald and Z11-16:OH. In the female antennae, only 7.53% of long trichoid sensilla responded to the sex pheromone components, A type sensilla were 3.64%, B type and C type sensilla were both 0.52%, D type sensilla were 1.30%, and 1.56% of the sensilla responded to all 3 components, which were named as F type sensilla. The responding long trichoid sensilla were located from the base to the terminal of the male antennae and from the base to the middle of the female antennae. The pheromone mixture (Z11-16:Ald : Z11-16:Ac : Z11-16:OH = 9.4 : 100 : 17) had a weakly repellent effect on female adults of P. xylostella. Our results lay the foundation for further studies on sex pheromone communications in P. xylostella., (© 2024 Institute of Zoology, Chinese Academy of Sciences.)

The gregarious lifestyle of lepidopteran larvae is diverse and shaped by a complex interplay of ecological and evolutionary factors. Our review showed that the larval-aggregation behavior has been reported in 23 lepidopteran families, indicating multiple evolution of this behavior. Some larvae live in sibling groups throughout all larval instars and even pupation stages, which may result from the kin-selection. In contrast, group fusion may occur among different sibling or foraging groups of larvae and form larger aggregates, and the gregariousness of these species might be driven by the group-selection. While group size and foraging patterns vary greatly across species, it is generally associated with improved larval survivorship and accelerated development. However, the advantages of group living, such as facilitating feeding activities, adjusting the temperature, and defending natural enemies, may diminish along with development, with strong intraspecific competition occurring at later instars, even when food is abundant. Therefore, the group sizes and fission-fusion dynamics of certain gregarious lepidopteran larvae may be a consequence of their cost-benefit balance depending on various biotic and abiotic factors. Trail and aggregation pheromones, silk trails, or body contact contribute to collective movement and group cohesion of gregarious lepidopteran larvae. However, frequent contact among group members may cause the horizontal transmission of pathogens and pesticides, which may bring an integrated pest management strategy controlling gregarious lepidopteran pests., (© 2024 Institute of Zoology, Chinese Academy of Sciences.)

Nanozymes are a new kind of material which has been applied since the beginning of this century, and its birth has promoted the development of chemistry, materials science, and biology. Nanozymes can be used as a substitute for natural enzyme and has a wide range of applications; therefore, it has attracted extensive attention from all sectors of the community, and the number of studies has constantly increasing. In this paper, we introduced the outstanding achievements in the field of nanozymes in recent years from the main function, the construction of nanozyme-based biosensors, and the treatment of ischemic stroke, and we also illustrated the internal mechanism and the catalytic principle. In the end, the obstacles and challenges in the future development of nanozymes were proposed., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Heortia vitessoides (Lepidoptera: Crambidae) is a severe pest of Aquilaria plants, which produce high-priced agarwood. The larval stage of this pest is gregarious, usually forming large aggregates during young instars and becoming solitary during the fifth instar. We hypothesize that the cuticle chemicals of young-instar H. vitessoides larvae could promote larval aggregating, whereas the cuticle chemicals of late-instar larvae would no longer attract young-instar larvae. In this study, two-choice tests were conducted to evaluate the effect of cuticle extracts of second- and fifth-instar H. vitessoides larvae on the aggregation preference of second-instar larvae. Results show that significantly more larvae aggregated on the leaves treated with the hexane extract of second-instar H. vitessoides larvae than on untreated leaves. However, the hexane extract of fifth-instar larvae had no significant effect on the aggregation preference of the second-instar conspecific larvae. Interestingly, acetone extracts of both second- and fifth-instar H. vitessoides larvae repelled the second-instar conspecific larvae throughout the 8 h experiment. Our study shows that cuticle chemicals of H. vitessoides larvae may play a role in the group dynamics of this pest, which may contribute to screening novel attractants and repellents for H. vitessoides . Detailed chemical analyses of the extracts and identification of the compounds involved in larval attracting and repelling would be valuable in future studies.

Bumblebees ( Bombus terrestris ) have been shown to engage in string-pulling behavior to access rewards. The objective of this study was to elucidate whether bumblebees display means-end comprehension in a string-pulling task. We presented bumblebees with two options: one where a string was connected to an artificial flower containing a reward and the other presenting an interrupted string. Bumblebees displayed a consistent preference for pulling connected strings over interrupted ones after training with a stepwise pulling technique. When exposed to novel string colors, bees continued to exhibit a bias towards pulling the connected string. This suggests that bumblebees engage in featural generalization of the visual display of the string connected to the flower in this task. If the view of the string connected to the flower was restricted during the training phase, the proportion of bumblebees choosing the connected strings significantly decreased. Similarly, when the bumblebees were confronted with coiled connected strings during the testing phase, they failed to identify and reject the interrupted strings. This finding underscores the significance of visual consistency in enabling the bumblebees to perform the task successfully. Our results suggest that bumblebees' ability to distinguish between continuous strings and interrupted strings relies on a combination of image matching and associative learning, rather than means-end understanding. These insights contribute to a deeper understanding of the cognitive processes employed by bumblebees when tackling complex spatial tasks., Competing Interests: CW, YL, CS, SD, CW, XW, HX, SD, JW, FP, LC No competing interests declared, (© 2024, Wen, Lu et al.)

Background: Osteoarthritis (OA) is a degenerative osteoarticular disease, involving genetic predisposition. How the risk variants confer the risk of OA through their effects on proteins remains largely unknown. Therefore, we aimed to discover new and effective drug targets for OA and its subtypes., Methods: A proteome-wide association study (PWAS) was performed based on OA and its subtypes genome-wide association studies (GWAS) summary datasets and the protein quantitative trait loci (pQTL) data. Subsequently, Mendelian randomization (MR) and colocalization analysis was conducted to estimate the associations between protein and OA risk. The replication analysis was performed in an independent dataset of human plasma pQTL data., Results: The abundance of seven proteins was causally related to OA, two proteins to knee OA and six proteins to hip OA, respectively. We replicated 2 of these proteins using an independent pQTL dataset. With the further support of colocalization, and higher ECM1 level was causally associated with a higher risk of OA and hip OA. Higher PCSK1 level was causally associated with a lower risk of OA. And higher levels of ITIH1, EFEMP1, and ERLEC1 were associated with decreased risk of hip OA., Conclusion: Our study provides new insights into the genetic component of protein abundance in OA and a promising therapeutic target for future drug development., (© 2024. The Author(s).)

Background: Nivolumab is an effective treatment option for advanced gastric cancer (GC). This study aimed to conduct a systematic review of existing literature to investigate the relationship between immune-related adverse events (irAEs) and the prognosis of patients with GC treated with nivolumab., Methods: We comprehensively searched four online literature databases: the Cochrane Central Register of Controlled Trials, PubMed, Embase, Web of Science, until 27 March 2024. The outcome measures of interest included: overall survival (OS), progression-free survival (PFS), hazard ratio (HR), median survival ratio (MSR), objective response rate (ORR), and disease control rate (DCR)., Results: A total of six studies, including 393 patients, met the eligibility criteria. The OS (pooled hazard ratio [HR] = 0.4, 95% confidence interval [CI]: 0.3-0.6, p < 0.05) and PFS (pooled HR = 0.5, 95% CI: 0.4-0.6, p < 0.05) of patients with irAEs were significantly superior to individuals without irAEs. The MSR for OS and PFS were 2.5 (95% CI: 1.5-4.1, p < 0.05) and 2.8 (95% CI: 1.9-4.1, p < 0.05), respectively. Regarding the ORR and DCR, we found that the development of irAEs was significantly associated with higher rates: patients with irAEs had an ORR of 24.7% compared to 6.4% in those without irAEs (risk ratio [RR] = 2.6, p < 0.05), and a DCR of 86.0% compared to 30.3% in those without irAEs (RR = 3.2, p < 0.05)., Conclusion: There appears to be a significant correlation between the development of irAEs and the better survival benefits with nivolumab in patients with GC., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022341396., Competing Interests: 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 Zhang, Tian and Wang.)

Ribociclib (RIB), a tyrosine kinase inhibitor, exhibits promising antitumor efficacy and controlled toxicity in HR+/HER2- breast cancer patients, which is closely related to the binding with plasma proteins. This study utilized a combination of spectroscopic techniques including UV spectroscopy, fluorescence spectroscopy, and circular dichroism (CD) as well as molecular docking and molecular dynamic simulation to clarify the binding mechanism between bovine serum albumin (BSA) and RIB. The findings demonstrated that RIB produced a 1:1 stoichiometric complex with BSA, which quenched BSA's fluorescence in the manner of the static quenching mechanism. Site labelling experiments pinpointed Site III on BSA as the primary binding site for RIB, a finding validated by molecular docking. Van der Waals forces and hydrogen bonding interactions as key drivers in the formation of RIB-BSA complexes, a conclusion supported by molecular docking. Molecular simulation studies suggested that the insertion of RIB into the hydrophobic cavity (Site III) of BSA induced subtle conformational changes in the BSA protein, and CD measurements confirmed alterations in BSA secondary structure content. Synchronous and three-dimensional fluorescence spectroscopy further demonstrated that RIB decreased the hydrophobicity of the microenvironment surrounding tyrosine and tryptophan residues. These findings offer valuable insights into the pharmacokinetics and structural modifications of RIB., 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.)

Rationale: Methamphetamine addiction is a persistent and intractable pathological learning and memory, whereas no approved therapeutics is available. However, few attentions have been paid to how associative learning participates in the formation of intractable memory related to drug addiction OBJECTIVES AND METHODS: To investigate the role of associative learning in methamphetamine addiction and the underlying neurobiological mechanism, methamphetamine self-administration, oral sucrose self-administration, chemogenetic neuromanipulation, and fiber photometry in mice were performed in this study., Results: We reported that associative learning increased methamphetamine-induced self-administration, but not oral sucrose self-administration. In addition, the enhancement of methamphetamine-induced self-administration was independent of more methamphetamine consumption, and remained with higher drug-taking and motivation in the absence of visual cues, suggesting the direct effects of the associative learning that enhanced methamphetamine-induced self-administration. Moreover, chemogenetic inactivation of the secondary visual cortex (V2) reduced the enhancement of the drug-taking induced by associative learning but did not alter sucrose-taking. Further fiber photometry of V2 neurons demonstrated that methamphetamine-associative learning elicits V2 neuron excitation, and sucrose-associative learning elicits V2 neuron inhibition., Conclusions: Therefore, this study reveals the neurobiological mechanism of V2 excitability underlying how associative learning participates in the formation of intractable memory related to drug addiction, and gives evidence to support V2 as a promising target for stimulation therapy for methamphetamine addiction., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The deep-sea remains the biggest challenge to biodiversity exploration, and anthropogenic disturbances extend well into this realm, calling for urgent management strategies. One of the most diverse, productive, and vulnerable ecosystems in the deep sea are sponge grounds. Currently, environmental DNA (eDNA) metabarcoding is revolutionising the field of biodiversity monitoring, yet complex deep-sea benthic ecosystems remain challenging to assess even with these novel technologies. Here, we evaluate the effectiveness of whole-community metabarcoding to characterise metazoan diversity in sponge grounds across the North Atlantic by leveraging the natural eDNA sampling properties of deep-sea sponges themselves. We sampled 97 sponge tissues from four species across four North-Atlantic biogeographic regions in the deep sea and screened them using the universal COI barcode region. We recovered unprecedented levels of taxonomic diversity per unit effort, especially across the phyla Chordata, Cnidaria, Echinodermata and Porifera, with at least 406 metazoan species found in our study area. These assemblages identify strong spatial patterns in relation to both latitude and depth, and detect emblematic species currently employed as indicators for these vulnerable habitats. The remarkable performance of this approach in different species of sponges, in different biogeographic regions and across the whole animal kingdom, illustrates the vast potential of natural samplers as high-resolution biomonitoring solutions for highly diverse and vulnerable deep-sea ecosystems., (© 2024. The Author(s).)

Background: Many scholars have performed several clinical studies have investigated the association between chronic periodontitis (CP) and chronic kidney disease (CKD). However, there are still differences between these research results, and there is no unified conclusion. Therefore, a systematic review is required to understand this issue fully., Aim: To explore the correlation between CP and CKD., Methods: Literature on the correlation between CP and CKD, as well as the clinical attachment level (CAL) and pocket probing depth (PPD) of CKD and non-CKD, were retrieved from PubMed, Embase, the Cochrane Library, and Web of Science repositories until January 2024. After the effective data were extracted, data processing and statistics were performed using Stata 12.0., Results: Of the 22 studies, 13 were related to CP and CKD, and 9 reported CAL and PPD in patients with CKD and healthy controls. Meta-analysis of the correlation between CP and CKD revealed that CKD probability in people with CP was 1. 54 times that of healthy individuals [relative risk = 1.54, 95% confidence interval (CI): 1.40-1.70], and CP incidence in patients with CKD was 1. 98 times that of healthy individuals [overall risk (OR) = 1.98, 95%CI: 1.53-2.57]. Meta-analysis of CAL and PPD evaluations between CKD patients and healthy individuals showed that CAL and PPD levels were higher in CKD patients [standard mean difference (SMD) of CAL = 0.65, 95%CI: 0.29-1.01; SMD of PPD = 0.33, 95%CI: 0.02-0.63]., Conclusion: A bidirectional association exists between CP and CKD. CKD risk is increased in CP patients and vice versa. Periodontal tissue or tooth loss risks increase over time in CKD patients., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: It is debatable whether the area of substantia nigra hyperechogenicity (SN+) in transcranial sonography (TCS) is related to Parkinson's disease (PD) severity. Iron deposition, which is associated with the formation of SN+, may have different effects on dopamine nerve function as PD progresses. However, little research has explored the association between the SN + area and disease severity of PD in stages., Methods: 612 PD patients with sufficient bone window were retrospectively included from a PD database, and disease severity was assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) scores. Based on the Hoehn and Yahr (H-Y) scale, we classified the patients into seven groups (H-Y stage 1, 1.5, 2, 2.5, 3, 4, and 5) and then analyzed the correlations between the SN + area and the UPDRS scores separately., Results: Our results indicated a U-shaped relationship between the initial-SN + area and disease severity in PD: In the H-Y stage 1 group, the initial-SN + area was negatively correlated with the UPDRS total score (r = - 0.456, p < 0.001) and UPDRS-III score (r = - 0.497, p < 0.001). No correlation was observed in the groups of H-Y stages 1.5, 2, and 2.5. In the groups of H-Y stage ≥ 3, the initial-SN + area was positively correlated with the UPDRS total score and UPDRS-III score, with strongest correlation in the H-Y stage 5 group (all p values < 0.05). Moreover, the larger SN + area and average SN + area showed a similar evolutionary trend of correlation with UPDRS total score and UPDRS-III score., Conclusions: Our study indicated a U-shaped correlation between the SN + area with the UPDRS total score and UPDRS-III score as H-Y stage progressed. The evolution of the correlation may reflect the evolution of underlying pathological mechanisms related to iron deposition in the substantia nigra., (© 2024. Fondazione Società Italiana di Neurologia.)

Fractures occur commonly with multiple injuries, and their incidence has increased in recent years. Trace amounts of cobalt are necessary for many living organisms as it stimulates hematopoiesis and improves bone health. However, cobalt is also toxic, as it might cause allergic reactions and tissue destruction. These factors limit the application of cobalt in some medical fields. We studied the tea polysaccode-cobalt complex (TPS-Co) prepared from Qingzhuan Dark Tea polysaccharides. We used 6-week-old Sprague-Dawley rats to establish a femoral fracture model and evaluated the effects of CoCl 2 and TPS-Co on the healing of femoral fractures. In this study, treatment with TPS-Co for the same content of cobalt intake decreased the side effects associated with CoCl 2 treatment and accelerated the healing of femoral fractures in rats. This treatment method promoted angiogenesis by upregulating the expression of vascular endothelial growth factor and hypoxia-inducible factor. Bone formation was promoted via the upregulation of the expression of bone morphogenetic protein 2 and serum bone alkaline phosphatase. TPS-Co was found to actively regulate bone and vascular systems, resulting in significant bone regeneration effects. Therefore, the Qingzhuan Dark Tea polysaccharide cobalt complex might be used as an additive or drug to promote fracture healing, and thus, it might have a huge market value.

Insects are the most diverse group of organisms in the animal kingdom, and some species exhibit complex social behaviors. Although research on insect object use is still in its early stages, insects have already been shown to display rich object-use behaviors. This review focuses on patterns and behavioral flexibility in insect object-use behavior, and the role of cultural evolution in the development of object-use behaviors. Object use in insects is not widespread but has been documented in a diverse set of taxa. Some insects can use objects flexibly and display various object-use patterns. Like mammals and birds, insects use objects in diverse activities, including foraging, predator defense, courtship, and play. Intelligence, pre-existing manipulative behaviors, and anatomical structure affect innovations in object use. In addition, learning and imitation are the main mechanisms underlying the spread of object-use behaviors within populations. Given that insects are one of the major animal groups engaging in object use, studies of insect object use could provide general insights into object use in the animal kingdom., (© 2023 The Authors. Insect Science published by John Wiley & Sons Australia, Ltd on behalf of Institute of Zoology, Chinese Academy of Sciences.)

Objectives: Pseudomonas aeruginosa and Acinetobacter baumannii are ranked as top-priority organisms by WHO. Antimicrobial peptides (AMPs) are promising antimicrobial agents that are highly effective against serious bacterial infections., Methods: In our previous study, a series of α-helical AMPs were screened using a novel multiple-descriptor strategy. The current research suggested that S24 exhibited strong antimicrobial activity against major pathogenic bacteria, and displayed minimal haemolysis, good serum stability and maintained salt resistance., Results: We found that S24 exerted an antimicrobial effect by destroying outer membrane permeability and producing a strong binding effect on bacterial genomic DNA that inhibits genomic DNA migration. Furthermore, S24 exerted a strong ability to promote healing in wound infected by P. aeruginosa, A. baumannii and mixed strains in a mouse model., Conclusions: Overall, S24 showed good stability under physiological conditions and excellent antimicrobial activity, suggesting it may be a potential candidate for the development of serious bacterial infection treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The purpose of this research was to characterize the microbiota of patients with psoriatic arthritis (PsA) and to compare the relationship between the microbiota and peripheral lymphocyte subsets and cytokines. We collected stool samples from 13 PsA patients and 26 sex- and age-matched healthy controls (HCs) and researched the gut microbiota by sequencing the V3-V4 variable region of the bacterial 16S rRNA gene with the Illumina Miseq PE300 system. Flow cytometry was used to assess the peripheral lymphocyte subsets in these participants. Record measures of disease activity such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Alpha and beta diversity were assessed using results from QIIME2. Panel demonstrated the average relative abundance of the different genera in PsA and HCs. Correlation between clinical parameters and the relative abundance of the genus in samples was assessed by the Pearson correlation analysis using R (version 4.0.1). Compared with HC, the abundance of gut microbiota (Chao 1 and ACE) decreased in patients with PsA, and the diversity of bacteria (Shannon and Simpson indices) also decreased in PsA (Fig. 1a). β Diversity analysis indicated differences in microbial communities between PsA and HC (Fig. 1b, r = 0.039, p = 0.264, ANOSIM). Furthermore, 18 bacterial groups were significantly different at the genus level in PsA compared to HCs (p < 0.05) (Fig. 2).In the phylum and genus, lymphocyte subsets and cytokines are associated with the microbiota. The gut microbiota of patients with PsA differs from HC, which was closely related to lymphocyte subsets., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Human pharyngeal squamous cell carcinoma (HPSCC) is the most common malignancy in the head and neck region, characterized by high mortality and a propensity for metastasis. Fucoxanthin, a carotenoid isolated from brown algae, exhibits pharmacological properties associated with the suppression of tumor proliferation and metastasis. Nevertheless, its potential to inhibit HPSCC proliferation and metastasis has not been fully elucidated. This study represents the first exploration of the inhibitory effects of fucoxanthin on two human pharyngeal squamous carcinoma cell lines (FaDu and Detroit 562), as well as the mechanisms underlying those effects. The results showed dose-dependent decreases in the proliferation, migration, and invasion of HPSCC cells after fucoxanthin treatment. Further studies indicated that fucoxanthin caused a significant reduction in the expression levels of proteins in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway, as well as the downstream proteins matrix metalloproteinase (MMP)-2 and MMP-9. Specific activators of PI3K/AKT reversed the effects of fucoxanthin on these proteins, as well as on cell proliferation and metastasis, in FaDu and Detroit 562 cells. Molecular docking assays confirmed that fucoxanthin strongly interacted with PI3K, AKT, mTOR, MMP-2, and MMP-9. Overall, fucoxanthin, a functional food component, is a potential therapeutic agent for HPSCC.

Purpose: Our team identified a new cardiac glycoside, Toxicarioside H (ToxH), in a tropical plant. Previous research has indicated the potential of cardenolides in mitigating inflammation, particularly in the context of NETosis. Therefore, this study sought to examine the potential of ToxH in attenuating allergic airway inflammation by influencing the immune microenvironment., Methods: An OVA-induced airway inflammation model was established in BALB/c mice. After the experiment was completed, serum, bronchoalveolar lavage fluid (BALF), and lung tissue samples were collected and further examined using H&E and PAS staining, flow cytometry, immunofluorescence observation, and Western blot analysis., Results: Treatment with ToxH was found to be effective in reducing airway inflammation and mucus production. This was accompanied by an increase in Th1 cytokines (IFN-γ, IL-2, and TNF-β), and the Th17 cytokine IL-17, while levels of Th2 cytokines (IL-4, IL-5, and IL-13) and Treg cytokines (IL-10 and TGF-β1) were decreased in both the bronchoalveolar lavage fluid (BALF) and the CD45 + immune cells in the lungs. Additionally, ToxH inhibited the infiltration of inflammatory cells and decreased the number of pulmonary CD44 + memory T cells, while augmenting the numbers of Th17 and Treg cells. Furthermore, the neutrophil elastase inhibitor GW311616A was observed to suppress airway inflammation and mucus production, as well as alter the secretion of immune Th1, Th2, Th17, and Treg cytokines in the lung CD45 + immune cells. Moreover, our study also demonstrated that treatment with ToxH efficiently inhibited ROS generation, thereby rectifying the dysregulation of immune cells in the immune microenvironment in OVA-induced allergic asthma., Conclusions: Our findings indicate that ToxH could serve as a promising therapeutic intervention for allergic airway inflammation and various other inflammatory disorders. Modulating the balance of Th1/Th2 and Treg/Th17 cells within the pulmonary immune microenvironment may offer an effective strategy for controlling allergic airway inflammation., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Studies have demonstrated that prior to puberty, girls have a lower incidence and severity of asthma symptoms compared to boys. This study aimed to explore the role of progesterone (P4), a sex hormone, in reducing inflammation and altering the immune microenvironment in a mouse model of allergic asthma induced by OVA. Female BALB/c mice with or without ovariectomy to remove the influence of sex hormones were used for the investigations. Serum, bronchoalveolar lavage fluid (BALF), and lung tissue samples were collected for analysis. The results indicated that P4 treatment was effective in decreasing inflammation and mucus secretion in the lungs of OVA-induced allergic asthma mice. P4 treatment also reduced the influx of inflammatory cells into the BALF and increased the levels of Th1 and Th17 cytokines while decreasing the levels of Th2 and Treg cytokines in both BALF and lung microenvironment CD45 + T cells. Furthermore, P4 inhibited the infiltration of inflammatory cells into the lungs, suppressed NETosis, and reduced the number of pulmonary CD4 + T cells while increasing the number of regulatory T cells. The neutrophil elastase inhibitor GW311616A also suppressed airway inflammation and mucus production and modified the secretion of immune Th1, Th2, Th17, and Treg cytokines in lung CD45 + immune cells. These changes led to an alteration of the immunological milieu with increased Th1 and Th17 cells, accompanied by decreased Th2, Treg, and CD44 + T cells, similar to the effects of P4 treatment. Treatment with P4 inhibited NETosis by suppressing the p38 pathway activation, leading to reduced reactive oxygen species production. Moreover, P4 treatment hindered the release of double-stranded DNA during NETosis, thereby influencing the immune microenvironment in the lungs. These findings suggest that P4 treatment may be beneficial in reducing inflammation associated with allergic asthma by modulating the immune microenvironment. In conclusion, this research indicates the potential of P4 as a therapeutic agent for ameliorating inflammation in OVA-induced allergic asthma mice., (© 2024. The Author(s).)

Monosialoganglioside GM1 (GM1) has long been used as a therapeutic agent for neurological diseases in the clinical treatment of ischemic stroke. However, the mechanism underlying the neuroprotective function of GM1 is still obscure until now. In this study, we investigated the effects of GM1 in ischemia and reperfusion (I/R) brain injury models. Middle cerebral artery occlusion and reperfusion (MCAO/R) rats were treated with GM1 (60 mg·kg -1 ·d -1 , tail vein injection) for 2 weeks. The results showed that GM1 substantially attenuated the MCAO/R-induced neurological dysfunction and inhibited the inflammatory responses and cell apoptosis in ischemic parietal cortex. We further revealed that GM1 inhibited the activation of NFκB/MAPK signaling pathway induced by MCAO/R injury. To explore its underlying mechanism of the neuroprotective effect, transcriptome sequencing was introduced to screen the differentially expressed genes (DEGs). By function enrichment and PPI network analyses, Sptbn1 was identified as a node gene in the network regulated by GM1 treatment. In the MCAO/R model of rats and oxygen-glucose deprivation and reperfusion (OGD/R) model of primary culture of rat cortical neurons, we first found that SPTBN1 was involved in the attenuation of I/R induced neuronal injury after GM1 administration. In SPTBN1-knockdown SH-SY5Y cells, the treatment with GM1 (20 μM) significantly increased SPTBN1 level. Moreover, OGD/R decreased SPTBN1 level in SPTBN1-overexpressed SH-SY5Y cells. These results indicated that GM1 might achieve its potent neuroprotective effects by regulating inflammatory response, cell apoptosis, and cytomembrane and cytoskeleton signals through SPTBN1. Therefore, SPTBN1 may be a potential target for the treatment of ischemic stroke., (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)

Objectives: This study explored the characteristics of muscle stiffness of lower gastrocnemius in resting and exercise states in patients with postural instability gait difficulty (PIGD) and tremor dominant (TD) Parkinson's disease patients using shear wave elastography (SWE)., Data and Methods: 75 PD patients from the Department of Parkinson's Disease Center in the Hospital from September 2021 to December 2022 were prospectively included, including 44 patients with PIGD and 31 with TD. In the same period, 40 healthy subjects matching gender and age were included as the control group. SWE was used to detect Young's modulus of both sides (right and left, R- and L-) of the lateral head of the gastrocnemius in resting (YM1) and exerciser states (YM2) in all participants and the absolute difference Young's modulus between resting and exercise state (ΔYM) was calculated., Results: R-YM2 and R-ΔYM were the highest in the normal controls, followed by the TD group, and lowest in the PIGD group. There were no differences in L-YM2 and L-ΔYM between the PIGD group and the TD group (all p > 0.05), but they were lower than those in the normal control group (all p < 0.05). In addition, R-YM2 and R-ΔYM were negatively correlated with disease duration and UPDRS III scores in the PIGD group (all p < 0.05). R-ΔYM has the highest value in the differential diagnosis of PIGD and TD patients. The area under the receiver operating characteristic curve (ROC) curve is 0.812 (95%CI, 0.730-0.893), and the diagnostic threshold is 120.5 Kpa with a sensitivity of 63.6%, a specificity of 90.1%, a positive predictive of 80%, and a negative predictive value of 80%., Conclusion: Shear wave elastography is a sensitive ultrasound method for evaluating muscle strength in patients with PIGD and TD. It also provides a new biological indicator to distinguish between different phenotypes of patients with PD., (© 2024. The Author(s) under exclusive licence to Belgian Neurological Society.)

Angiogenesis plays a critical role in many pathological processes, including irreversible blindness in eye diseases such as retinopathy of prematurity. Endothelial mitochondria are dynamic organelles that undergo constant fusion and fission and are critical signalling hubs that modulate angiogenesis by coordinating reactive oxygen species (ROS) production and calcium signalling and metabolism. In this study, we investigated the role of mitochondrial dynamics in pathological retinal angiogenesis. We showed that treatment with vascular endothelial growth factor (VEGF; 20 ng/ml) induced mitochondrial fission in HUVECs by promoting the phosphorylation of dynamin-related protein 1 (DRP1). DRP1 knockdown or pretreatment with the DRP1 inhibitor Mdivi-1 (5 μM) blocked VEGF-induced cell migration, proliferation, and tube formation in HUVECs. We demonstrated that VEGF treatment increased mitochondrial ROS production in HUVECs, which was necessary for HIF-1α-dependent glycolysis, as well as proliferation, migration, and tube formation, and the inhibition of mitochondrial fission prevented VEGF-induced mitochondrial ROS production. In an oxygen-induced retinopathy (OIR) mouse model, we found that active DRP1 was highly expressed in endothelial cells in neovascular tufts. The administration of Mdivi-1 (10 mg·kg -1 ·d -1 , i.p.) for three days from postnatal day (P) 13 until P15 significantly alleviated pathological angiogenesis in the retina. Our results suggest that targeting mitochondrial fission may be a therapeutic strategy for proliferative retinopathies and other diseases that are dependent on pathological angiogenesis., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Cell fate determination is an intricate process which is orchestrated by multiple regulatory layers including signal pathways, transcriptional factors, epigenetic modifications, and metabolic rewiring. Among the sophisticated epigenetic modulations, the repressive mark H3K27me3, deposited by PRC2 (polycomb repressive complex 2) and removed by demethylase KDM6, plays a pivotal role in mediating the cellular identity transition through its dynamic and precise alterations. Herein, we overview and discuss how H3K27me3 and its modifiers regulate pluripotency maintenance and early lineage differentiation. We primarily highlight the following four aspects: 1) the two subcomplexes PRC2.1 and PRC2.2 and the distribution of genomic H3K27 methylation; 2) PRC2 as a critical regulator in pluripotency maintenance and exit; 3) the emerging role of the eraser KDM6 in early differentiation; 4) newly identified additional factors influencing H3K27me3. We present a comprehensive insight into the molecular principles of the dynamic regulation of H3K27me3, as well as how this epigenetic mark participates in pluripotent stem cell-centered cell fate determination., Competing Interests: 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., (© 2024 The Authors.)

Background: For Rheumatoid Arthritis (RA), a long-term chronic illness, it is essential to identify and describe patient subtypes with comparable goal status and molecular biomarkers. This study aims to develop and validate a new subtyping scheme that integrates genome-scale transcriptomic profiles of RA peripheral blood genes, providing a fresh perspective for stratified treatments., Methods: We utilized independent microarray datasets of RA peripheral blood mononuclear cells (PBMCs). Up-regulated differentially expressed genes (DEGs) were subjected to functional enrichment analysis. Unsupervised cluster analysis was then employed to identify RA peripheral blood gene expression-driven subtypes. We defined three distinct clustering subtypes based on the identified 404 up-regulated DEGs., Results: Subtype A, named NE-driving, was enriched in pathways related to neutrophil activation and responses to bacteria. Subtype B, termed interferon-driving (IFN-driving), exhibited abundant B cells and showed increased expression of transcripts involved in IFN signaling and defense responses to viruses. In Subtype C, an enrichment of CD8+ T-cells was found, ultimately defining it as CD8+ T-cells-driving. The RA subtyping scheme was validated using the XGBoost machine learning algorithm. We also evaluated the therapeutic outcomes of biological disease-modifying anti-rheumatic drugs., Conclusions: The findings provide valuable insights for deep stratification, enabling the design of molecular diagnosis and serving as a reference for stratified therapy in RA patients in the future., Competing Interests: 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 Chang, Feng, Hao, Zhang, Zhao, Li, Zhao, Han, He and Wang.)

The efficacy of rosuvastatin in reducing allergic inflammation has been established. However, its potential to reduce airway remodeling has yet to be explored. This study aimed to evaluate the efficacy of rosuvastatin in reducing airway inflammation and remodeling in a mouse model of chronic allergic asthma induced by sensitization and challenge with OVA. Histology of the lung tissue and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) showed a marked decrease in airway inflammation and remodeling in mice treated with rosuvastatin, as evidenced by a decrease in goblet cell hyperplasia, collagen deposition, and smooth muscle hypertrophy. Furthermore, levels of inflammatory cytokines, angiogenesis-related factors, and OVA-specific IgE in BALF, plasma, and serum were all reduced upon treatment with rosuvastatin. Western blotting was employed to detect AMPK expression, while immunohistochemistry staining was used to observe the expression of remodeling signaling proteins such as α-SMA, TGF-β, MMP-9, and p-AMPKα in the lungs. It was found that the activity of 5'-adenosine monophosphate-activated protein kinase alpha (AMPKα) was significantly lower in the lungs of OVA-induced asthmatic mice compared to Control mice. However, the administration of rosuvastatin increased the ratio of phosphorylated AMPK to total AMPKα, thus inhibiting the formation of new blood vessels, as indicated by CD31-positive staining mainly in the sub-epithelial region. These results indicate that rosuvastatin can effectively reduce airway inflammation and remodeling in mice with chronic allergic asthma caused by OVA, likely due to the reactivation of AMPKα and a decrease in angiogenesis., Competing Interests: The authors declare that there is no conflict of interest to declare., (Copyright: © 2024 Zhang 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.)

This study investigated the mechanism by which fucoxanthin acts as a novel ferroptosis inducer to inhibit tongue cancer. The MTT assay was used to detect the inhibitory effects of fucoxanthin on SCC-25 human tongue squamous carcinoma cells. The levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and total iron were measured. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to assess glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2-related factor 2 (Nrf2), Keap1, solute carrier family 7 member 11 (SLC7A11), transferrin receptor protein 1 (TFR1), p53, and heme oxygenase 1 (HO-1) expression. Molecular docking was performed to validate interactions. Compared with the control group, the activity of fucoxanthin-treated SCC-25 cells significantly decreased in a dose- and time-dependent manner. The levels of MMP, GSH, and SOD significantly decreased in fucoxanthin-treated SCC-25 cells; the levels of ROS, MDA, and total iron significantly increased. mRNA and protein expression levels of Keap1, GPX4, Nrf2, and HO-1 in fucoxanthin-treated cells were significantly decreased, whereas levels of TFR1 and p53 were significantly increased, in a concentration-dependent manner. Molecular docking analysis revealed that binding free energies of fucoxanthin with p53, SLC7A11, GPX4, Nrf2, Keap1, HO-1, and TFR1 were below -5 kcal/mol, primarily based on active site hydrogen bonding. Our findings suggest that fucoxanthin can induce ferroptosis in SCC-25 cells, highlighting its potential as a treatment for tongue cancer.

High cadmium (Cd) concentrations widely occured in selenium (Se)-rich soils, which has been an important obstacle in the usage of Se-rich soils. There is still no special information detailing the enrichment process and mechanism of Cd in Se-rich soils. 4474 soils and 21 rocks in Lanshan District were sampled to detect its enrichment process. The surface soils have Cd concentrations of 0.01-9.41 mg·kg -1 (an average of 0.16 mg·kg -1 ). The soil Cd concentrations were significantly correlated with soil Se concentrations. The relatively higher-Cd surface soils are distributed in Lower-middle Ordovician carbonate areas with Se-rich soils and Quaternary areas with typical anthropic activities. Surface soils in Ordovician carbonate area have the highest Cd concentrations. Soil Cd concentrations are significantly correlated with sulfophil elements (Zinc (Zn), Copper (Cu), Molybdenum (Mo), Lead (Pb) and Arsenic (As) etc.), Ca (Calcium) concentrations and soil organic carbon (SOC). The soil and rock samples from different geological units also confirmed soil Cd concentrations developing from Ordovician carbonates were higher than those from other rocks. The results indicate the soil Cd concentrations were the complex consequences of bedrock, soil-forming processes and anthropogenic activities. Higher Ca concentrations and more reduction environments result in high-Cd bedrock. CaCO 3 leaching and alkaline pH, which are the special soil-forming process of carbonates, enrich Cd in soils. Agricultural and industrial activities also affect soil Cd concentrations. An enrichment model of Cd in Se-rich soils is forwarded., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

We develop a new type of heterostructure nanocomposite made of reduced graphene oxide-boron carbon nitride nanosheets (rGO-BCN) by B-C covalent bonds. The rGO-BCN nanocomposite delivers a large specific surface and excellent electrochemical properties, and is then constructed into flexible fabric-based high-performance supercapacitor electrodes based on the microfluidic electrospinning technology.

Ursolic acid has gradually attracted much attention due to its unique pharmacological activities and valuable market value in recent years. Currently, ursolic acid is mostly extracted from loquat leaves, but the plant extraction method has low yield and high cost, and chemical synthesis is not readily available, so the biosynthesis method provides a new source for ursolic acid. α-amyrin acts as the main precursor for the synthesis of ursolic acid, and its yield is positively correlated with ursolic acid yield. Oxidosqualene cyclase(OSC) belongs to a multigene family which can catalyze the common precursor 2,3-oxidosqualene to generate different types of triterpene backbones, and plays a decisive role in the synthesis of triterpenoids. However, there are fewer reported key genes catalyzing the synthesis of α-amyrin in medicinal plants, and the yield and proportion of α-amyrin in the catalyzed products have always been a focus of research. In this study, ItOSC2, MdOSC1, AaOSC2 and CrAS, four enzymes capable of catalyzing the production of α-amyrin from 2,3-oxidosqualene, were cloned from Iris tectorum, Malus domestica, Artemisia annua and Catharanthus roseus, subject to sequence alignment and phylogenetic tree analyses, and transformed into Saccharomyces cerevisiae as plasmids. After 7 days of fermentation, the yield and proportions of α-amyrin, β-amyrin and ergosterol were measured. Finally, AaOSC2 with the best ability to catalyze the generation of α-amyrin was filtered out, providing a key gene element for the later construction of engineered yeast strains with high production of α-amyrin and ursolic acid.

Background: The pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) with comorbid asthma remains unclear., Objective: To assess upper and lower airway unity and identify a possible common pathogenesis in CRSwNP with asthma., Methods: This study analyzed the expression of proteins and metabolites in nasal lavage fluid cells (NLFCs) and induced sputum cells (ISCs). Differentially expressed proteins and their function-related metabolites in the upper and lower airways of patients having CRSwNP with or without asthma were identified; relevant signaling pathways were analyzed, and key pathway-related proteins were identified. Parallel reaction monitoring was used to verify these target proteins., Results: Protein or metabolite expression between NLFCs and ISCs was highly correlated and conservative on the basis of expression profiles and weighted gene coexpression network analysis. There were 17 differentially coexpressed proteins and their function-related 13 metabolites that were identified in the NLFCs and ISCs of CRSwNP, whereas 11 proteins and 11 metabolites were identified in CRSwNP with asthma. An asthma pathway was involved in the copathogenesis of upper and lower airways in whether CRSwNP or CRSwNP with asthma. The asthma pathway-related proteins proteoglycan 2 and eosinophil peroxidase, as the core of the protein-metabolism interaction networks between the upper and lower airways, were both highly coexpressed in NLFCs and ISCs in patients having either CRSwNP or CRSwNP with asthma by parallel reaction monitoring validation., Conclusion: Proteomics and metabolomics reveal upper and lower airway unity. Asthma pathway-related proteins proteoglycan 2 and eosinophil peroxidase from the upper airway could be used to assess the potential risk of lower airway dysfunction in CRSwNP., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Aims: Penicilazaphilone C (PAC) is hypothesized to potentially serve as a therapeutic treatment for allergic airway inflammation by inhibiting the NLRP3 inflammasome and reducing oxidative stress., Methods: An allergic asthma model was induced in female BALB/c mice of the OVA, OVA+PAC, OVA+PAC+LPS, and OVA+Dex groups by sensitizing and subsequently challenging them with OVA. The OVA+PAC and Normal+PAC groups were treated with PAC, while the OVA+PAC+LPS group also received LPS. The OVA+Dex group was given dexamethasone (Dex). Samples of serum, bronchoalveolar lavage fluid (BALF), and lung tissue were collected for histological and cytological analysis., Results: Allergic mice treated with PAC or Dex showed inhibited inflammation and mucus production in the lungs. There was a decrease in the number of inflammatory cells in the BALF, lower levels of inflammatory cytokines in the serum and BALF, and a reduction in the protein expression of NLRP3, ASC, cleaved caspase-1, IL-1β, activated gasdermin D, MPO, Ly6G, and ICAM-1. Additionally, oxidative stress was reduced, as shown by a decrease in MDA and DCF, but an increase in SOD and GSH. Treatment with PAC also resulted in a decrease in pulmonary memory CD4+ T cells and an increase in regulatory T cells. However, the positive effects seen in the PAC-treated mice were reversed when the NLRP3 inflammasome was activated by LPS, almost returning to the levels of the Sham-treated mice., Significance: PAC acts in a similar way to anti-allergic inflammation as Dex, suggesting it may be a viable therapeutic option for managing allergic asthma inflammation., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: Transcranial sonography has been used as a valid neuroimaging tool to diagnose Parkinson's disease (PD). This study aimed to develop a modified transcranial sonography (TCS) technique based on a deep convolutional neural network (DCNN) model to predict Parkinson's disease., Methods: This retrospective diagnostic study was conducted using 1529 transcranial sonography images collected from 854 patients with PD and 775 normal controls admitted to the Second Affiliated Hospital of Soochow University (Suzhou, Jiangsu, China) between September 2019 and May 2022. The data set was divided into training cohorts (570 PD patients and 541 normal controls), and the validation set (184 PD patients and 234 normal controls). Using these datasets, we developed four different DCNN models (ResNet18, ResNet50, ResNet152, and DenseNet121). We then assessed their diagnostic performance, including the area under the receiver operating characteristic (AUROC) curve, specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), and F1 score and compared with traditional diagnostic criteria., Results: Among the 1529 TCS images, 570 PD patients and 541 normal controls from 4 of 6 sonographers of the TCS team were selected as the training cohort, and 184 PD patients and 234 normal controls from the other 2 sonographers were chosen as the validation cohort. There were no sex and age differences between PD patients and normal control subjects in the training and validation cohorts (P values > 0.05). All DCNN models achieved good performance in distinguishing PD patients from normal control subjects on the validation datasets, with diagnostic AUROCs and accuracy of 0.949 (95% CI 0.925, 0.965) and 86.60 for the RestNet18 model, 0.949 (95% CI 0.929, 0.971) and 87.56 for ResNet50, 0.945 (95% CI 0.931, 0.969) and 88.04 for ResNet152, 0.953 (95% CI 0.935, 0.971) and 87.80 for DenseNet121, respectively. On the other hand, the diagnostic accuracy of the traditional diagnostic method was 82.30. The accuracy of all DCNN models was higher than that of traditional diagnostic method. Moreover, the 5k-fold cross-validation results in train datasets showed that these DCNN models are robust., Conclusion: The developed transcranial sonography-based DCNN models performed better than traditional diagnostic criteria, thus improving the sonographer's accuracy in diagnosing PD., (© 2023. Fondazione Società Italiana di Neurologia.)

Snake venoms, comprising a complex array of protein-rich components, an important part of which are snake venom metalloproteinases (SVMPs). These SVMPs, which are predominantly isolated from viperid venoms, are integral to the pathology of snakebites. However, SVMPs derived from elapid venoms have not been extensively explored, and only a handful of SVMPs have been characterized to date. Atrase A, a nonhemorrhagic P-III class metalloproteinase from Naja atra venom, exhibits weak proteolytic activity against fibrinogen in vitro but has pronounced anticoagulant effects in vivo. This contrast spurred investigations into its anticoagulant mechanisms. Research findings indicate that atrase A notably extends the activated partial thromboplastin time, diminishes fibrinogen levels, and impedes platelet aggregation. The anticoagulant action of atrase A primarily involves inhibiting coagulation factor VIII and activating the endogenous fibrinolytic system, which in turn lowers fibrinogen levels. Additionally, its effect on platelet aggregation further contributes to its anticoagulant profile. This study unveils a novel anticoagulant mechanism of atrase A, significantly enriching the understanding of the roles of cobra venom metalloproteinases in snake venom. Furthermore, these findings underscore the potential of atrase A as a novel anticoagulant drug, offering insights into the functional evolutions of cobra venom metalloproteinases., Competing Interests: 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., (© 2024 The Author(s).)

Previous studies have demonstrated that associative learning and experience play important roles in the string-pulling of bumblebees (Bombus terrestris). However, the features of the target (artificial flower with sugar reward) and the string that bees learn in such tasks remain unknown. This study aimed to explore the specific aspects of the string-flower arrangement that bumblebees learn and how they prioritize these features. We show that bumblebees trained with string-pulling are sensitive to the flower stimuli; they exhibit a preference for pulling strings connected to flowers over strings that are not attached to a target. Additionally, they chose to pull strings attached to flowers of the same color and shape as experienced during training. The string feature also plays a crucial role for bumblebees when the flower features are identical. Furthermore, bees prioritized the features of the strings rather than the flowers when both cues were in conflict. Our results show that bumblebees solve string-pulling tasks by acquiring knowledge about the characteristics of both targets and strings, and contribute to a deeper understanding of the cognitive processes employed by bees when tackling non-natural skills., (© 2024 Institute of Zoology, Chinese Academy of Sciences.)

The aim of this study was to investigate whether the therapeutic effect of theabrownin extracted from Qingzhuan tea (QTB) on metabolic dysfunction-associated steatosis liver disease (MASLD) is related to the regulation of intestinal microbiota and its metabolite short-chain fatty acids (SCFAs). Mice were divided into four groups and received normal diet (ND), high-fat diet (HFD) and HFD+QTB (180, 360 mg/kg) for 8 weeks. The results showed that QTB significantly reduced the body weight of HFD mice, ameliorated liver lipid and dyslipidemia, and increased the level of intestinal SCFAs in HFD mice. The results of 16 S rRNA showed that the relative abundance of Bacteroides, Blautia and Lachnoclostridium and their main metabolites acetate and propionate were significantly increased after QTB intervention. The relative abundance of Colidextribacter, Faecalibaculum and Lactobacillus was significantly reduced. QTB can also significantly up-regulate the expression of ATGL, PPARα, FFAR2 and FFAR3, and inhibit the expression of LXRα, SREBP-1c, FAS and HMGCR genes. This makes it possible to act as a prebiotic to prevent MASLD., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Rationale and Objectives: This study aims to develop and validate a computed tomography (CT)-based radiomics nomogram for pre-operatively predicting central lymph node metastasis (CLNM) in patients with papillary thyroid microcarcinoma (PTMC) and explore the underlying biological basis by using RNA sequencing data., Methods: This study trained 452 PTMC patients across two hospitals from January 2012 to December 2020. The sets were randomly divided into the training (n = 339), internal test (n = 86), external test (n = 27) sets. Radiomics features were extracted from primary lesion's pre-operative CT images for each patient. After screening for features, five algorithms such as K-nearest neighbor, logistics regression, linear-support vector machine (SVM), Gaussian SVM, and polynomial SVM were used to establish the radiomics models. The performance of these five algorithms was evaluated and compared directly to radiologist's interpretation (CT-reported lymph node status). The radiomics signature score (Rad-score) was generated using a linear combination of the selected features. By combining the clinical risk factors and Rad score, a radiomics nomogram was established and compared with Rad-score and clinical model. The performance of the nomogram was evaluated based on the receiver operating characteristic (ROC) curve, calibration curve, and the decision curve analysis (DCA). The potential biological basis of nomogram was revealed by performing genetic analysis based on the RNA sequencing data., Results: A total of 25 radiomic features were ultimately selected to train the machine learning models, and the five machine learning models outperformed the radiologists' interpretation by achieving area under the ROC curves (AUCs) ranging from 0.606 to 0.730 in the internal test set. By incorporating the Rad score and clinical risk factors (sex, age, tumor-diameter, and CT-reported lymph node status), this nomogram achieved AUCs of 0.800 and 0.803 in the internal and external test set, which were higher than that of the Rad-score and clinical model, respectively. Calibration curves and DCA also showed that the nomogram had good performance. As for the biological basis exploration, in patients predicted by nomogram to be PTC patients with CLMN, 109 genes were dysregulated, and some of them were associated with pathways and biological processes such as tumor angiogenesis., Conclusion: This radiomics nomogram successfully identified CLNM on pretreatment imaging across multiple institutions, exceeding the diagnostic ability of radiologists and had the potential to be integrated into clinical decision making as a non-invasive pre-operative tool., 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.)

Zanthoxylum nitidum is frequently used as a traditional Chinese medicine and food supplement. Our previous study revealed that its constituent compounds were able to inhibit cancer cell proliferation. In our continuous exploration of bioactive compounds in Z. nitidum , we isolated ten alkaloids ( 1 - 10 ), including one new natural compound ( 1 ), and nine known alkaloids ( 2-10 ), from an ethanolic extract of the whole plant. The chemical structures were elucidated based on a combination of comprehensive NMR and HRESIMS analyses. Compounds 5, 8 and 10 exhibited significant antiproliferative effects against A549 cancer cell lines. We further elucidated the underlying molecular mechanisms of the antiproliferative activity of compound 8 in A549 human lung cancer cells. Compound 8 was found to induce cell cycle arrest in the G0/G1 phase via p53 activation and CDK4/6 suppression. Compound 8 also effectively inhibited cell migration through the modulation of the epithelial-mesenchymal transition (EMT), as indicated by the expression of biomarkers, such as N-cadherin downregulation and E-cadherin upregulation. Compound 8 significantly suppressed the activation of the EGFR/AKT/mTOR signalling pathway in A549 cells. These results indicate that alkaloid 8 from Z. nitidum has potential to be a lead antiproliferative compound in cancer cells.

Although the synthesis of mechanically interlocked molecules has been extensively researched, selectively constructing homogeneous linear [4]catenanes remains a formidable challenge. Here, we selectively constructed a homogeneous linear metalla[4]catenane in a one-step process through the coordination-driven self-assembly of a bidentate benzothiadiazole derivative ligand and a binuclear half-sandwich rhodium precursor. The formation of metalla[4]catenanes was facilitated by cooperative interactions between strong sandwich-type π-π stacking and non-classical hydrogen bonds between the components. Moreover, by modulating the aromatic substituents on the binuclear precursor, two homogeneous metalla[2]catenanes were obtained. The molecular structures of these metallacatenanes were unambiguously characterized by single-crystal X-ray diffraction analysis. Additionally, reversible structural transformation between metal-catenanes and the corresponding metallarectangles could be achieved by altering their concentration, as confirmed by mass spectrometry and NMR spectroscopy studies., (© 2024 Wiley‐VCH GmbH.)

We designed a common garden design to collect data on female reproductive traits from three populations of the southern grass lizard Takydromus sexlineatus , testing the hypothesis that a species-specific pattern of seasonal shifts in reproductive allocation should be shared by geographically separated populations. Of the seven examined traits, six differed among populations, with four of the six also differing among successive clutches. Females grew longer during the breeding season and produced more eggs in the first clutch than in the subsequent clutches; egg size was unchanged throughout the breeding season. After removing the influence of female size or postpartum body mass we found the following. First, postpartum body mass, clutch mass, and relative clutch mass were greater in the Wuzhishan population than in the Shaoguan and Zhaoqing populations. Second, egg size was greatest in the Wuzhishan population and smallest in the Zhaoqing population. Third, clutch size was greatest in the Wuzhishan population and smallest in the Shaoguan population. Females did not trade-off egg size against number within each population × clutch combination. Our study validates the hypothesis tested, supports the conventional view that reproductive output is highly linked to maternal body size in lizards, and follows the classic prediction that females with different amounts of resources to invest in reproduction should give priority to adjusting the total number rather than size of their offspring.

A series of designed stilbenoid-flavanone hybrids featuring sp 3 -hybridized C2 and C3 atoms of C-ring was evaluated against colorectal cancers presented compounds 4, 17, and 20 as the most potential compounds among explored compounds. Evaluation of the anticancer activity spectrum of compounds 4, 17, and 20 against diverse solid tumors presented compounds 17 and 20 with interesting anticancer spectrum. The potencies of compounds 17 and 20 were assessed in comparison with FDA-approved anticancer drugs. Compound 17 was the, in general, the most potent showing low micromolar GI 50 values that were more potent than the standard FDA-approved drugs against several solid tumors including colon, brain, skin, renal, prostate and breast tumors. Compound 17 was subjected for evaluation against normal cell lines and was subjected to a mechanism study in HCT116 colon cancer cells which presented it as an inhibitor of Wnt signaling pathway triggering G 2 /M cell cycle arrest though activation of p53-p21 pathway as well as intrinsic and extrinsic apoptotic death of colon cancer cells. Compound 17 might be a candidate for further development against diverse solid tumors including colon 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.)