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Build-up of free cholesterol (FC) substantially contributes to the development and severity of non-alcoholic fatty liver disease (NAFLD). Here, we investigate the specific mechanism by which FC induces liver injury in NAFLD and propose a novel therapeutic approach using dihydrotanshinone I (DhT). Rather than cholesterol ester (CE), we observed elevated levels of total cholesterol, FC, and alanine transaminase (ALT) in NAFLD patients and high-cholesterol diet-induced NAFLD mice compared to those in healthy controls. The FC level demonstrated a positive correlation with the ALT level in both patients and mice. Mechanistic studies revealed that FC elevated reactive oxygen species level, impaired the function of lysosomes, and disrupted lipophagy process, consequently inducing cell apoptosis. We then found that DhT protected mice on an HCD diet, independent of gut microbiota. DhT functioned as a potent ligand for peroxisome proliferator-activated receptor α (PPARα), stimulating its transcriptional function and enhancing catalase expression to lower reactive oxygen species (ROS) level. Notably, the protective effect of DhT was nullified in mice with hepatic PPARα knockdown. Thus, these findings are the first to report the detrimental role of FC in NAFLD, which could lead to the development of new treatment strategies for NAFLD by leveraging the therapeutic potential of DhT and PPARα pathway., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

This study evaluated the effects of postharvest ripening (0-6 days, D0-6) on cell wall pectin profile, infrared-assisted hot air-drying characteristics, and sugar content. Results showed that during postharvest ripening progress, the content of water-soluble pectin (WSP) and chelate-soluble pectin (CSP) increased while the content of Na 2 CO 3 -soluble pectin (NSP) and hemicellulose (HC) decreased. In addition, the average molecular weight of WSP increased while the average molecular weight of NSP decreased. Secondly, the drying time of plums with different postharvest ripening periods was in the order: D3 < D4 < D2 < D1 < D0 < D5 < D6. Furthermore, the sugar content of dried plums was mainly influenced by drying time, with three stages of sugar changes observed, tied to moisture content: (1) Sucrose hydrolyzes (50-85%); (2) Fructose and glucose degrade (15-50%); (3) Sorbitol degrades (15-42%). These findings indicate that the transformation of cell wall pectin profile during the postharvest ripening process alters drying behavior and regulates the sugar content of dried plums. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Galacturonic acid (PubChem CID: 439215); Acetone (PubChem CID: 180); Distilled water (PubChem CID: 962); Trans-1,2-Diaminocyclohexane-N, N, N, N'-tetraacetic acid (PubChem CID: 2723845); Na 2 CO 3 (PubChem CID: 10340); Glucose (PubChem CID: 5793); fructose (PubChem CID: 2723872) sucrose (PubChem CID: 5988) sorbitol (PubChem CID: 5780) and Sodium borohydride (PubChem CID: 4311764)., 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.)

Hydrothermal cracking involves the conversion of organic waste into efficient fertilizer through hydrolysis at temperatures ranging from 180 to 220 °C and pressures of 1.5 to 2.45 MPa, which offers significant advantages in shortening the production cycle, enhancing efficiency, and decomposing antibiotics. As a result, it holds immense practical value for promoting organic fertilizer manufacturing processes globally. The products derived from hydrothermal cracking can be categorized into solid and liquid components. Extensive research has focused on the composition and use of solids, while studies on liquids have mainly examined basic characteristics. The study aimed to comprehensively analyze the components in liquid products prepared through hydrothermal cracking and evaluate their suitability as liquid fertilizers. Specifically, we employed rigorous analytical techniques to accurately identify and quantify medium and trace elements, organic acids, amino acids, and plant growth regulators. Furthermore, we carried out a planting experiment to assess the yield and soil changes following the application of liquid products in maize cultivation. The experimental data revealed that the liquid product contained abundant medium and trace elements, along with 6.22 g/L free amino acids and 9.22 g/L organic acids. It is noteworthy that this liquid product contained 1.22 × 10 5  pg/mL ABA, 6.26 × 10 3  pg/mL IAA, 1.07 × 10 2  pg/mL IBA, and 3.60 × 10 -2  pg/mL GA3. The utilization of this liquid product has the potential to enhance the disease resistance of maize crops and promote the accumulation of nitrate nitrogen in the soil. By understanding the composition of liquid products via hydrothermal cracking, valuable insights can be gained into their potential benefits for agricultural and ecological applications., 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 dual inhibition of histone lysine-specific demethylase 1 (LSD1) and histone deacetylase (HDAC) has emerged as a promising strategy for cancer therapy. In this study, we report the discovery of novel 5-cyano-3-phenylindole-based LSD1/HDAC dual inhibitors, evaluated through both in vitro and in vivo assays. Among these inhibitors, compound 20c was identified as particularly potent, exhibiting high inhibitory activity against LSD1 (IC 50 = 39.0 nM) and HDAC1/2/3/6/8 (IC 50 = 1.4, 1.0, 1.3, 2.9, and 16.0 nM, respectively). Compound 20c effectively modulated the expression of biomarkers associated with LSD1 and HDAC inhibition and demonstrated superior antiproliferative activity compared to SAHA and 4SC-202 across multiple colorectal cancer cell lines. Following pharmacokinetic studies, 20c was further assessed in HCT-116 and HT-29 xenograft mouse models. It demonstrated significantly enhanced antitumor efficacy compared to SAHA, without causing observable toxicity. These findings highlight the potential of LSD1/HDAC dual inhibitors for the treatment of malignant cancers.

Background: Cognitive impairment induced by a high-fat diet (HFD) is common, but its mechanism is largely unknown. Huang-Lian-Jie-Du (HLJD) decoction is a classical and powerful prescription in China. It consists of four medicinal plants and is widely used in traditional Chinese medicines (TCM). Studies have shown that HLJD decoction is effective in treating obesity, depression, and so on. However, the therapeutic mechanism of HLJD is still poorly understood., Purpose: Our study aimed to explore whether inflammatory factors and Trem2/Dap12/Syk pathway are involved in this process and whether HLJD treatment can repair cognitive impairment in HFD-induced obesity., Methods: To obtain the obese mice, male mice were treated with HFD (60 Kcal% fat) for 16 weeks. After an additional eight weeks, HLJD decoction was administered orally at doses of 4 and 8 g/kg daily for eight weeks. The mice were then subjected to four behavior tests. Aβ42, total Tau, inflammatory-related, and microglial dysregulation-related markers expression were measured. Molecular docking analysis was also conducted to predict the interaction of the chemical constituents of HLJD with human TREM2, DAP12, and SYK. HLJD at doses of 12.5, 25, and 50 µg/mL or limonin at concentrations of 12.5, 25, and 50 µM were used to treat BV2 cells for 24 h. CCK8 assay and Trem2, Dap12, Syk, and p-Syk expression were measured., Results: Our study revealed that cognitive impairment was evident in mice treated with HFD, indicating the impact of obesity on cognitive function. The expression of Aβ42 and total Tau in the hippocampus (HIP) was significantly higher in obese (HFD-V) mice compared to normal control (NC-V) mice. The Il6, Il1b, and Il10 mRNA expression levels were also markedly increased in the HIP of obese mice. Furthermore, Trem2, Dap12, p-Syk, and Iba1 expression were elevated in the HIP of obese mice. Importantly, HLJD treatment was found to repair cognitive impairment and lower the protein expression of Aβ42, Tau, Trem2, Dap12, p-Syk, and the expression of Il6, Il1b, and Il10 mRNA in HIP of HFD-V mice. The increased expression of Trem2, Dap12, p-Syk, and Iba1 in HIP after HFD consumption could be reduced after receiving HLJD decoction. The compound Limonin showed a well-predicted binding energy with TREM2, DAP12, and SYK. BV2 cells with HLJD or limonin detected the mRNA expressions of Trem2/Dap12. HLJD at 25 and 50 µg/mL decreased Trem2, Dap12, and p-Syk protein levels in BV2 cells., Conclusion: These results reveal that HLJD treatment could alleviate cognitive impairment in HFD-induced obese mice by controlling the activation of the Trem2/Dap12 pathway and reducing Syk phosphorylation in HIP microglia. HLJD and limonin suppressed Trem2/Dap12/Syk signaling pathway in BV2 cells. HLJD therapy might represent a novel treatment for patients with cognitive impairment induced by obesity., Competing Interests: Declaration of competing interest All the authors declare that this research involves no potential commercial or financial relationships and no conflict of interest., (Copyright © 2024. Published by Elsevier GmbH.)

Amid growing concerns regarding gout and hyperuricemia associated with high-protein and purine-rich diets, the need for effective prevention and management strategies with minimal side effects has become increasingly critical. This study evaluates the potential of three commonly consumed plant-based functional foods, Chrysanthemum morifolium , Perilla frutescens , and Sophora japonica , inhibiting xanthine oxidase (XO) and adenosine deaminase (ADA), key enzymes in uric acid metabolism. Results from hyperuricemia model mice indicate that this blend significantly reduces serum uric acid levels, mirroring the efficacy of conventional prevention and management strategies such as allopurinol but with fewer adverse effects. Liquid chromatography-mass spectrometry (LC-MS) analysis confirms that flavonoids are the primary bioactive agents, exhibiting a strong affinity for XO. These findings highlight the viability of integrating plant-based functional foods into comprehensive gout management strategies, underscoring their role in enhancing patient health through dietary innovation.

Fibroblast activation plays an important role in the occurrence and development of idiopathic pulmonary fibrosis (IPF), which is a progressive, incurable, and fibrotic lung disease. However, the underlying mechanism of fibroblast activation in IPF remains elusive. Here, we showed that the expression levels of STX11 and SNAP25 were downregulated in the lung tissues from patients with IPF and mice with bleomycin (BLM)-induced lung fibrosis as well as in the activated fibroblasts. Upregulation of STX11 or SNAP25 suppressed TGF-β1-induced activation of human lung fibroblasts (HLFs) via promoting autophagy. However, they failed to suppress fibroblast actviation when autophagy was blocked with the use of chloroquine (CQ). In addition, STX11 or SNAP25 could inhibit TGF-β1-induced fibroblast proliferation and migration. In vivo, overexpression of STX11 exerted its protective role in the mice with BLM-induced lung fibrosis. STX11 and SNAP25 mutually promoted expression of each other. Co-IP assay indicated that STX11 has an interaction with SNAP25. Mechanistically, STX11-SNAP25 interaction activated fibroblast autophagy and further inhibited fibroblast activation via blocking the PI3K/AKT/mTOR pathway. Overall, the results suggested that STX11-SNAP25 interaction significantly inhibited lung fibrosis by promoting fibroblast autophagy and suppressing fibroblast activation via blocking the PI3K/ATK/mTOR signaling pathway. Therefore, STX11 serves as a promising therapeutic target in IPF., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Asparagales, the largest monocot order, is renowned for its ecological, economic, and medicinal significance. Here, we leverage transcriptome data from 455 Asparagales species to explore the phylogeny of Asparagales. Moreover, we investigate the evolutionary patterns of the genes involved in allium flavor formation. We not only establish a robust bifurcating phylogeny of Asparagales but also explore their reticulate relationships. Notably, we find that eight genes involved in the biosynthesis of allium flavor compounds underwent expansion in Allium species. Furthermore, we observe Allium-specific mutations in one amino acid within alliinase and three within lachrymatory factor synthase. Overall, our findings highlight the role of gene expansion, increased expression, and amino acid mutations in driving the evolution of Allium-specific compounds. These insights not only deepen our understanding of the phylogeny of Asparagales but also illuminate the genetic mechanisms underpinning specialized compounds., (© 2024. The Author(s).)

Metal-organic frameworks (MOFs) have been widely used for separation, but amplifying subtle differences between similar molecules to achieve effective separation remains a great challenge. In this study, we utilize the fluorescent molecule uranine (Ura) to modulate the pores of zeolitic-imidazolate framework 8 (ZIF8), creating an unusual throttle effect. By monitoring fluorescence intensity changes in Ura, the transport diffusion process could be quantified to reveal the diffusion constant of solvents. When we pushed the Ura occupancy to its limit (from 59% to 76% and 98%), the diffusion rate decreases by 2 orders of magnitude. Most importantly, there is a significant dissymmetry between the two-way exchange rates of solvents, and the rates of H 2 O and D 2 O became distinguishable. Such unusual throttle effects disappear at low Ura occupancy of 59% and 76%. We believe that the throttle effect with small-molecule loading could provide a universal design principle for MOF-based applications, especially for isotope separation.

The practical application of rechargeable zinc-air batteries faces challenges stemming from inadequate bifunctional catalysts, contradictory gas-liquid-solid three-phase interfaces, and an ambiguous fundamental understanding. Herein, we propose a chameleon-like bifunctional catalyst comprising ruthenium single-atoms grafted onto nickel-iron layer double hydroxide (Ru SA -NiFe LDH). The adaptive oxidation of Ru SA -NiFe LDH to oxyhydroxide species (Ru SA -NiFeOOH) during charging exposes active sites for the oxygen evolution reaction, while reversible reduction to NiFe LDH during discharge exposes active sites for the oxygen reduction reaction. Additionally, a hierarchical air cathode featuring hydrophilic and hydrophobic layers facilitates the reversible conversion between Ru SA -NiFe LDH and Ru SA -NiFeOOH, expedites oxygen bubble desorption, and suppresses carbon corrosion. Consequently, our zinc-air batteries demonstrate a high charge/discharge capacity of 100 mAh cm -2 per cycle, a voltage gap of 0.67 V, and an extended cycle life of 2400 h at 10 mA cm -2 . We comprehensively elucidate the catalytic reaction thermodynamics and kinetics for the air cathode through electrode potential decoupling monitoring, oxygen bubble desorption tracking, and carbon content quantification., (© 2024. The Author(s).)

Increasing evidence indicated that purinergic signalling involved in electroacupuncture (EA)-induced analgesia. Whether purinergic P2Y 14 receptor contributes to EA-mediated analgesia remains unclear. Here, we report that the expression of P2Y 14 receptor in the hindlimb region of the primary somatosensory cortex (S1HL) was significantly upregulated on Complete Freund's Adjuvant (CFA)-induced pain model mice, while was downregulated after EA treatment (2 Hz frequency, 1 mA intensity, and 30 min duration) at "Zusanli" (also named ST36 acupoint). EA-mediated analgesia could be reversed by injection of P2RY 14 agonist uridine diphosphate glucose (UDPG) into the bilateral S1HL, while prolonged by injection of P2RY 14 antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPTN). It suggested that EA may alleviate inflammatory pain by downregulating the expression of P2RY 14 in the S1HL., (© 2024. The Author(s).)

Increasing evidence supports the crucial role of Epithelial-Mesenchymal Transition (EMT) in cancer invasion and metastasis. N-acetylglucosaminyltransferase V (MGAT5), which is associated with multiantenna glycosylation, can contribute to tumorigenesis, yet its specific role in promoting colorectal cancer (CRC) metastasis remains unclear. Bioinformatics analysis of CRC datasets revealed that elevated MGAT5 expression was associated with EMT and a poor prognosis. In vitro experiments confirmed the pivotal role of MGAT5 as an EMT regulator in CRC cells. MGAT5 overexpression stimulated cell proliferation and migration, while MGAT5 knockdown had the opposite effect. Mechanistically, MGAT5 promoted EMT through multiantenna glycosylation of ZO-1, promoting its ubiquitination and reducing its expression. Clinically, MGAT5 upregulation in the CRC TMA correlated negatively with ZO-1 expression, which is indicative of malignancy and a poor prognosis. This study revealed that MGAT5 promotes EMT in CRC via interactions between multiple antenna glycosylation products and ZO-1 ubiquitination/degradation, indicating that MGAT5 could serve as a promising therapeutic target for CRC., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Artemisia capillaris Thunb. (ACT) is a plant in the Asteraceae family. Its traditional effects are to clear away dampness and heat, promote gallbladder and reduce jaundice. Traditional Chinese medicine believes that MASLD is a damp-heat syndrome. The group's previous study showed that Artemisia capillaris Thunb. Water Extract (ACTE) has an improved effect on MASLD., Aim of the Study and Methods: In order to further understand its mechanism of action, this study established a mouse MASLD model and a HepG2 cell lipid droplet model, combined small RNA sequencing and miRNA transfection experiments, to explore the mechanism of ACTE to improve MASLD by modulating miRNA-targeted mRNA. Non-targeted metabolomics method was used to detect and analyze ACTE., Results: This study screened miR-34a-5p and confirmed its target mRNA-Sirtuin 1 (Sirt1). MASLD induced high expression of miR-34a-5p and low expression of Sirt1, and ACE reversed these changes. When overexpressing miR-34a-5p or knocking down Sirt1, the effect of ACE in reducing PO (palmitic acid and oleic acid complex)-induced lipid accumulation in HepG2 cells was attenuated. ACTE reduces the expression of FASN, SCD1, ACC, and SREBP-1c, promotes the expression of CPT-1 and HSL, thereby reducing lipid accumulation., Conclusions: ACTE activates Sirt1 by inhibiting the expression of miR-34a-5p, thereby reducing liver lipid accumulation and improving HFD-induced MASLD. These findings highlight the potential of ACTE in reducing weight, controlling obesity, and improving lipid metabolism 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. Published by Elsevier B.V.)

The incidence of atrial fibrillation (AF) increases with age; however, the precise mechanisms by which aging elevates AF risk and the effective biomarkers for managing AF in elderly patients remain unclear. We analyzed plasma samples from 100 elderly AF patients, 100 young and 100 elderly patients without atrial fibrillation (NAF), along with left atrial tissues obtained from both AF and NAF patients following valve replacement. Our findings indicate reduced levels of β-OHB and citrate synthase (CS) activity in elderly AF patients compared to their NAF counterparts. Statistical analysis revealed a protective association between β-OHB and CS activity concerning the occurrence of elderly AF. Furthermore, atrial tissues from elderly AF patients exhibited mitochondrial dysfunction, structural remodeling, and low-voltage areas. These results suggest that dysregulation of β-OHB levels and CS activity may contribute to aging-related AF by affecting mitochondrial function and atrial remodeling, highlighting their potential as diagnostic biomarkers for this condition., (© 2024. The Author(s).)

Training a neural network-based biomedical named entity recognition (BioNER) model usually requires extensive and costly human annotations. While several studies have employed multi-task learning with multiple BioNER datasets to reduce human effort, this approach does not consistently yield performance improvements and may introduce label ambiguity in different biomedical corpora. We aim to tackle those challenges through transfer learning from easily accessible resources with fewer concept overlaps with biomedical datasets. In this paper, we proposed GERBERA, a simple-yet-effective method that utilized a general-domain NER dataset for training. Specifically, we performed multi-task learning to train a pre-trained biomedical language model with both the target BioNER dataset and the general-domain dataset. Subsequently, we fine-tuned the models specifically for the BioNER dataset. We systematically evaluated GERBERA on five datasets of eight entity types, collectively consisting of 81,410 instances. Despite using fewer biomedical resources, our models demonstrated superior performance compared to baseline models trained with multiple additional BioNER datasets. Specifically, our models consistently outperformed the baselines in six out of eight entity types, achieving an average improvement of 0.9% over the best baseline performance across eight biomedical entity types sourced from five different corpora. Our method was especially effective in amplifying performance on BioNER datasets characterized by limited data, with a 4.7% improvement in F1 scores on the JNLPBA-RNA dataset.

Traumatic brain injury (TBI) exhibits high prevalence and mortality, but current treatments remain suboptimal. Traditional Chinese medicine (TCM) has long been effectively used for TBI intervention. Moreover, the recently discovered iron-dependent cell death pathway, known as ferroptosis, characterized by lipid peroxidation, as a key target in TCM-based treatments for TBI. This review provides a comprehensive overview of the latest advancements in TCM strategies targeting ferroptosis in TBI therapy, covering natural product monomers, classic formulas, and acupuncture/moxibustion. The review also addresses current challenges and outlines future research directions to further advance the development and application of TBI management strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: The popularity of caffeinated foods and beverages poses risks of high caffeine exposure among Chinese children and adolescents. Nevertheless, there is a lack of national assessments on their caffeine consumption., Objective: To estimate daily caffeine intake and analyze time trends among Chinese children and adolescents., Methods: The study subjects were participants of the China Health and Nutrition Survey in 2004, 2006, 2009 and 2011, and the National Food and Beverage Consumption Survey in 2014 and 2018. Caffeine content was determined using chromatographic instrument. The Monte Carlo simulation was utilized to estimate daily caffeine intake and the Kruskal-Wallis test was used to analyze differences between population characteristics. To examine yearly trends in caffeine intake from 2004 to 2018, the partial Mann-Kendall test was applied., Results: The median daily caffeine intake of Chinese children and adolescents was 0.17 (95%CI: 0.15-0.20) mg/kg BW/day. Main contributors were tea (55.52%), sodas (19.52%) and tea beverages (10.37%). Approximately 4.68% of individuals consumed caffeine exceeding 2.5 mg/kg BW/day. Higher caffeine intake was observed in adolescents aged 12-17 years, males, and consumers residing in northeastern China. While no significant overall yearly trends in caffeine intake were detected from 2004 to 2018, there was an increase in intake driven by beverage consumption between 2006 and 2014., Conclusion: This study provided a national assessment of caffeine consumption among Chinese children and adolescents. Caffeinated beverages like tea, soda, and tea beverages emerged as major contributors to caffeine intake. These findings could contribute to the regulation of caffeine consumption and the promotion of healthy habits among children and adolescents., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ling Yong reports financial support was provided by China National Center of Technology Innovation for Dairy and Chinese Institute of Food Science and Technology., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The accumulation and systemic propagation of senescent cells contributes to physiological aging and age-related pathology. However, which cell types are most susceptible to the aged milieu and could be responsible for the propagation of senescence has remained unclear. Here we found that physiologically aged bone marrow monocytes/macrophages (BMMs) propagate senescence to multiple tissues, through extracellular vesicles (EVs), and drive age-associated dysfunction in mice. We identified peroxisome proliferator-activated receptor α (PPARα) as a target of microRNAs within aged BMM-EVs that regulates downstream effects on senescence and age-related dysfunction. Demonstrating therapeutic potential, we report that treatment with the PPARα agonist fenofibrate effectively restores tissue homeostasis in aged mice. Suggesting conservation to humans, in a cohort study of 7,986 participants, we found that fenofibrate use is associated with a reduced risk of age-related chronic disease and higher life expectancy. Together, our findings establish that BMMs can propagate senescence to distant tissues and cause age-related dysfunction, and they provide supportive evidence for fenofibrate to extend healthy lifespan., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The majority of natural fungal β-glucans exhibit diverse biological functionalities, such as immunomodulation and anti-inflammatory effects, attributed to their distinctive helix or highly branched conformation This study utilized β-glucan with helix conformation and high-viscosity extracted from Hericium erinaceus, employing freeze-thaw and solvent exchange strategies to induce multiple hydrogen bonding between molecules, thereby initiating the self-assembly process of β-glucan from random coil to stable helix conformation without chemical modifications. Subsequently, the natural bioactive compound tannic acid was introduced through physical entanglement, imparting exceptional antioxidant properties to the hydrogel. The HEBG/TA hydrogel exhibited injectable properties, appropriate mechanical characteristics, degradability, temperature-responsive tannic acid release, antioxidant activity, and hemostatic potential. In vivo experiments using skin full-thickness defect and deep second-degree burn wound models demonstrated significant therapeutic efficacy, including neovascularization, and tissue regeneration. Moreover, the HEBG/TA hydrogel demonstrated its ability to regulate cytokines by effectively inhibiting the production of inflammatory mediators (TNF-α, IL-6), while simultaneously enhancing the expression of cell proliferation factor KI-67 and markers associated with angiogenesis such as CD31 and α-SMA. This study highlights the potential of combining natural β-glucan with bioactive molecules for skin repair., Competing Interests: Declaration of competing interest The authors declared that there were no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Pathogenic bacteria infection, especially Clostridium perfringens (C. perfringens), markedly threatened the health of animals, and further caused huge economic loss. In this study, Bacillus licheniformis HJ0135 (BL) was used. Oxford cup bacteriostatic test and inhibitory rate test were conducted to evaluate the antibacterial ability of BL. Results showed the strongest inhibitory role of BL on C. perfringens (P < 0.05). Afterwards, 540 one-day-old yellow-feather broilers (32.7 ± 0.2 g) were randomly allocated into 3 groups, including CON group (basal diet), CP group (basal diet + 1 × 10 9 CFU C. perfringens in gavage), and BL + CP group (basal diet containing 7.5 × 10 6 CFU/g BL + 1 × 10 9 CFU C. perfringens in gavage). At d 70, broilers in the CP and BL + CP groups were treated with C. perfringens by continuously oral administration for 5 d. The experiment lasted for 75 d. The serum, immune organs, jejunal mucosa, and cecal contents were collected for analysis. In vivo experiment showed that BL supplementation markedly improved (P < 0.05) BW, ADG, thymus index, serum immunoglobins and antioxidases, reduced feed conversion ratio (FCR) and serum pro-inflammatory cytokines of C. perfringens-infected broilers. Furthermore, the increased jejunal injury and levels of pro-inflammatory cytokines, decreased gene expressions of tight junction proteins in the jejunal mucosa were significantly alleviated (P < 0.05) by BL. More importantly, the activation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome was inhibited (P < 0.05) by BL to further attenuate jejunal damage. Besides, BL supplementation markedly increased (P < 0.05) the cecal isobutyric acid and isovaleric acid. Microbial analysis showed that BL changed the composition and relative abundances of microbiota in the cecal contents (P < 0.05), especially the short chain fatty acids (SCFAs)-producing bacteria including Eubacterium&#95;coprostanoligenes&#95;group, Megamonas, Faecalibacterium, and Lactobacillus, which further protected against C. perfringens-induced jejunal inflammation in broilers. Our study laid a theoretical basis for the application of probiotics in lessening C. perfringens-related diseases in poultry farming., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Objective: The aim of this study is to systematically examine and compare the characteristics distinguishing colorectal adenomatous polyps from normal mucosal intestinal microbiota., Methods: A total of 30 specimens were obtained from patients diagnosed with colorectal adenomatous polyps (adenoma group) who underwent endoscopic removal at Wenzhou People's Hospital between September 2021 and November 2021. Concurrently, 30 normal mucosal specimens were collected from patients without adenomatous polyps (control group). Subsequently, microbiome total DNA extraction was carried out, followed by PCR amplification targeting the V3-V4 region of the 16S rDNA. High-throughput sequencing was conducted using the Illumina MiSeq platform. Subsequent to sequencing, bioinformatics analysis was used to assess the diversity, composition, and functional aspects of the intestinal microbiota in both study groups., Results: A notable dissimilarity in the microbiota structure was identified, specifically within the transverse colon, between these two groups ( P  < 0.05). Species composition analysis revealed that Escherichia , Fusobacterium , and Bacteroides were predominant bacteria in both groups, with Escherichia and Enterobacter displaying significant differences at the genera level between the control group and the adenoma group ( P  < 0.05). Correlation analysis and functional prediction demonstrated substantial disparities in interactions among dominant intestinal microbial genera within patients from both groups. Additionally, it was discovered that the intestinal microbiomes in patients in the adenoma group exhibited a significantly higher pathogenic potential., Conclusion: Upon conducting a comprehensive analysis, it was discerned that the microbiota present in the transverse colon of the control group exhibited distinctive characteristics that may contribute to the maintenance of intestinal health., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder affecting millions of people worldwide, with no effective treatment currently available. In recent decades, various traditional Chinese medicines (TCMs) and their active ingredients have shown the potential to attenuate the pathogenesis of AD in cellular and animal models. However, the effects of TCM formulas, which are typically administered in practice, have been less studied. This study aims to investigate the therapeutic effects of several formulas consisting of 4 components herbal components: catalpol, puerarin, gastrodin, and borneol, on streptozotocin (STZ)-induced AD models in cells and rats. The new object recognition (NOR), elevated plus maze (EMP), and Morris water maze (MWM) tests were used to evaluate the cognitive functions of rats. Golgi staining, Haematoxylin and Eosin (HE) staining, and Nissl staining analyses were employed assess the physiology of hippocampal tissues. Gene expression profiles were analyzed used transcriptomics and reverse transcription quantitative polymerase chain reaction analysis, while protein expression levels were determined using immunoblotting, immunohistochemical, and immunofluorescence. The production of cytokines was evaluated with enzyme-linked immunosorbent assay. The results demonstrated that the combined administration of these 4 components (CPGB) had superior mitigating effects on AD cell model, as evidenced by the reduced pro-inflammatory cytokine production and decreased deposition of Aβ protein. Further in vivo and in vitro experiments confirmed that varying doses of CPGB formula effectively ameliorated STZ-induced cognitive deficits, as shown by NOR, MWM, and EMP tests, as well as pathological changes in hippocampal tissues and a 3-dimensional brain neurovascular unit (3D-NVU) model, including decreased deposition of Aβ protein and formation of plaques. Transcriptome sequencing and analysis identified 35 genes with significantly altered expression levels due to STZ and CPGB treatment in hippocampal tissues, which were enriched in the Tlr4/Myd88/NF-κB signaling pathway. Interference with this pathway significantly influenced the therapeutic effects of CPGB in the 3D-NVU model. Collectively, these findings suggest that the combined administration of catalpol, puerarin, gastrodin, and borneol offers superior therapeutic effects on AD by modulating the Tlr4/Myd88/NF-κB signaling pathway. This study strengthens the theoretical foundation for using TCMs to treat AD, proving new insights and references for alleviating and treating AD., 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 Ren, Tang, Yuan, Liu, Zhou, Xiao, Wu, Chen, Chen, Wang, Xue and Xu.)

The slow rate of anaerobic microbial dechlorination in natural environments limits the application of polychlorinated biphenyl (PCB) bioremediation. Anaerobic digested sludge (ADS), abundant in nutrients and microorganisms, could be an effective additive to improve microbial dechlorination. This research investigates the influence of ADS on Aroclor 1260 dechlorination performance, microbial community composition, and the abundance of functional genes. Moreover, further enrichment of organohalide-respiring bacteria (OHRB) was examined using tetrachloroethene (PCE) as the electron acceptor, followed by the serial dilution-to-extinction method in conjunction with resuscitation promoting factor (Rpf) supplementation. The results demonstrated that the addition of 5 g/L ADS achieved more extensive and efficient dechlorination of PCBs. ADS enhanced the removal of meta- and para-chlorine without significantly changing the dechlorination pathways. The abundances of dechlorinators, including Dehalobium and Dehalobacter within the Chloroflexi and Firmicutes phyla, as well as non-dechlorinators from the Desulfobacterota, Euryarchaeota, and Bacteroidetes phyla, were significantly increased with ADS amendment. Similarly, an increased abundance of bacteria, OHRB, reductive dehalogenase (RDase) genes, and archaeal 16S rRNA genes was observed. Additionally, obligate OHRB, such as Dehalobacter and Dehalobium, were further enriched. These findings indicate that ADS effectively enhances microbial reductive dechlorination and highlight the potential for enriching and isolating OHRB with Rpf., 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.)

While a hippocampal-cortical dialogue is generally thought to mediate memory consolidation, which is crucial for engram function, how it works remains largely unknown. Here, we examined the interplay of neural signals from the retrosplenial cortex (RSC), a neocortical region, and from the hippocampus in memory consolidation by simultaneously recording sharp-wave ripples (SWRs) of dorsal hippocampal CA1 and neural signals of RSC in free-moving mice during the delayed spatial alternation task (DSAT) and subsequent sleep. Hippocampal-RSC coordination during SWRs was identified in nonrapid eye movement (NREM) sleep, reflecting neural reactivation of decision-making in the task, as shown by a peak reactivation strength within SWRs. Using modified generalized linear models (GLMs), we traced information flow through the RSC-CA1-RSC circuit around SWRs during sleep following DSAT. Our findings show that after spatial training, RSC excitatory neurons typically increase CA1 activity prior to hippocampal SWRs, potentially initiating hippocampal memory replay, while inhibitory neurons are activated by hippocampal outputs in post-SWRs. We further identified certain excitatory neurons in the RSC that encoded spatial information related to the DSAT. These neurons, classified as splitters and location-related cells, showed varied responses to hippocampal SWRs. Overall, our study highlights the complex dynamics between the RSC and hippocampal CA1 region during SWRs in NREM sleep, underscoring their critical interplay in spatial memory consolidation., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Ruiqing Hou et al.)

Urban road traffic environmental stress impacts outdoor population health, with oxidative damage serving as an early indicator of xenobiotic exposure. Polycyclic aromatic hydrocarbons (PAHs) as priority carcinogens pose significant public health burden, yet knowledge remains limited regarding the endogenous metabolic alternations associated with oxidative DNA injury. This cross-sectional study focused on the cohort consisting of 109 sanitation workers ("traffic exposure group") and 112 demographics-matched common residents ("controls") in South China. The goal was to elucidate the occurrence of internal exposure to nine hydroxyl PAHs, and the interrelations with oxidative DNA damage (indicated by 8-hydroxy-2'-deoxyguanosine, 8-OHdG) by linear mixed-effect regression model. T-test and orthogonal partial least squares discriminant analysis were used to determine differential metabolites in non-targeted metabolomics. Results revealed outdoor workers suffered from the heavier PAH exposure burden and exhibited a stronger dose-dependent correlation with 8-OHdG, evidenced by the higher regression coefficient (0.244, 95% CI: 0.154-0.334) than controls (0.203, 95% CI: 0.079-0.328). In total 42 differential endogenous metabolites witnessed significant expression under traffic emission scenario, mainly implicated in phenylalanine, tyrosine and tryptophan biosynthesis. The down-expressed uric acid was the unique metabolite that inversely correlated with the increased intake of ∑ 8 PAH especially in cases. Partially attributed to the traffic-derived PAHs, the dysregulated amino acid, nicotinamide, purine, and steroid hormones metabolic pathways encompassing 11 metabolites were determined as underlying biomarkers in mediating DNA damage. Notably, our findings proposed uric acid may act as a potential antioxidant, as evidenced by the negative correlation with 8-OHdG. The study illustrates outcomes of metabolomics can collaboratively indicate DNA oxidative damage caused by PAHs linked to urban traffic exposure, which holds significant implications for future toxicological research., 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 Ltd.)

Objectives: This study aimed to examine patient delay, diagnosis delay and treatment performance among patients with tuberculosis (TB) in Shanghai, China in 2018-2020 focusing on disparities between migrant and local patients with TB., Design: Mixed-method study., Setting and Participants: Quantitative data were collected from the TB information management system in Shanghai; 17 533 bacteriologically confirmed and clinically diagnosed patients with pulmonary TB registered in 2018-2020 were included. Qualitative interviews were conducted with TB administrators (n=3) and community healthcare providers (two groups, n=10 in total) from Shanghai., Main Outcome Measures: Patient delay, diagnosis delay and treatment completion were examined by resident type using descriptive analysis and logistic regressions. Qualitative interviews were conducted to understand factors associated with the disparities., Results: From 2018 to 2020, migrant patients with TB accounted for 44.40% of total cases. There was no significant difference in patient delay between migrant and local patients (18.47 days on average). 22.12% of migrants and 16.52% of locals experienced diagnosis delays exceeding 14 days, respectively. After adjusting for all variables, migrant patients (OR 1.30, 95% CI 1.18 to 1.44) and initial care seeking at general hospitals (OR 3.76, 95% CI 3.45 to 4.09) were associated with a higher probability of diagnosis delay. 93.9% of migrant patients and 89.4% of the local patients had a successful TB treatment without statistically significant difference after adjusting for all variables. Qualitative interviews revealed a standard approach to managing patients with TB in Shanghai no matter their resident type. Young migrant patients who were able to maintain their jobs in Shanghai often had better treatment adherence. Despite patients' COVID-19 fear and limited care access in 2020, TB treatment minimally affected for both due to community-based case management., Conclusions: Migrant patients were more likely to experience diagnosis delay. It should improve awareness and knowledge of TB among healthcare professionals at general hospitals to mitigate the risk of diagnosis delay., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

GWASs have linked the 3p21.1 locus, which is associated with the expression levels of NEK4, to bipolar disorder. Here, we use integrative analyses of GWAS statistics and eQTL annotations to establish that elevated NEK4 expression in the hippocampus is associated with an increased risk of bipolar disorder. To further study this association, we generate transgenic male mice that conditionally overexpress NEK4 in the pyramidal neurons of the adult forebrain, or use AAV to overexpress NEK4 in the dorsal hippocampus. Compared to the control mice, male mice of both strains exhibit a shift from a diurnal anxiety state to a nocturnal normal or anxiolytic-like state. Overexpression of NEK4 also affects the circadian fluctuations in dendritic spine morphology and synaptic structure. Furthermore, we show that treatment with lithium ameliorates the effects of NEK4 overexpression in male mice. We then perform phosphoproteomic analyses to demonstrate that the diurnal and nocturnal phosphoproteomic profiles of male control and NEK4 overexpressing mice are different. These results suggest that male mice with different NEK4 expression levels may recapitulate some of the core features observed in patients with bipolar disorder, indicating that interruption of the homeostatic dynamics of synapses may underlie the emotional swings in bipolar disorder., (© 2024. The Author(s).)

Bedaquiline (BDQ) has shown efficacy in shortening treatment duration and enhancing treatment success rates for multidrug-resistant tuberculosis (MDR-TB), thereby prompting widespread adoption. However, resistance to BDQ has emerged. This study aimed to identify genetic characteristics associated with decreased susceptibility to BDQ, using a public database to aid in the detection of resistant strains. Seventy-one BDQ-resistant and 929 BDQ-susceptible isolates from the open-source CRyPTIC database were selected for analysis. Variant calling was conducted via the clockwork pipeline. Univariate logistic regression was performed for each gene mutation, followed by LASSO regression for further variant selection. Ultimately, a multiple linear regression model was developed using log 2 -transformed Minimum Inhibitory Concentration values as the dependent variable, with variant selection refined through stepwise regression based on the Akaike Information Criterion. Ten gene mutations were significantly associated with reduced BDQ susceptibility, including two key gene mutations: Rv0678&#95;141&#95;ins&#95;1 and Rv1979c&#95;D249E, with effect estimates of 1.76 (95 % CI: 0.67-2.84) and 1.69 (95 % CI: 0.22-3.17), respectively. Other implicated genes included Rv2699c&#95;-84&#95;del&#95;1, hsaB&#95;I179T, mmpL9&#95;T241A, pncA&#95;C14R, Rv0373c&#95;G621S, Rv0893c&#95;L27F, Rv1770&#95;A4D, and Rv3428c&#95;S327C. This study identified ten gene mutations linked to decreased susceptibility to BDQ, providing a reference for developing a comprehensive catalog of BDQ-resistant genes., Competing Interests: Declaration of competing interest The authors declare that no competing interests exist., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: This study aimed to investigate the clinical safety and efficacy of laparoscopic lateral suspension (LLS) with mesh in the treatment of severe anterior and apical pelvic organ prolapse (POP) Chinese women with a 2-year follow-up., Methods: We conducted an observational cohort study. Sixty patients who presented apical (uterovaginal or vault) and anterior prolapse at stage 3 or higher were enrolled. The LLS surgical procedure was performed in accordance with Dubuisson standard operation. The objective and subjective cures as well as the surgery-related complications were evaluated. The POP-related questionnaires were used to evaluate the quality of life before operation and at 24 months after operation follow-up., Results: Objective cure rates at 2 years of follow-up were 88.3% for the anterior compartment, 100% for the apical compartment and 93.3% for the posterior compartment. The subjective cure rate reached to 93.3%. There were statistically significant lower scores of the pelvic floor impact questionnaire-7 (PFIQ-7) and the pelvic floor distress inventory-short form-20 (PFDI-20) for all women after surgery and they exhibited similar scores of the pelvic organ prolapsed-urinary incontinence sexual questionnaire-12 (PISQ-12) (P = 0.317). And no significant difference was demonstrated in international consultation on the incontinent questionnaire short form (ICI-Q-SF) (P = 0.551). No major complications associated with LLS were observed in our study., Conclusion: We consider that LLS with mesh operation is safe, feasible and effective to correct severe apical and anterior POP after 2-year follow-up., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purposes: Osimertinib, one of the third-generation EGFR -tyrosine kinase inhibitors (TKIs) designed to target EGFR T790M mutation, significantly improves the prognosis of lung cancer. However, drug resistance still happens and MET amplification is responsible for one of the main causes. Fluorescence in situ hybridization (FISH) is the gold standard for MET amplification detection, but fundamentally limited by observer subjectivity. Herein, we assessed the value of next-generation sequencing (NGS) method in MET amplification detection in non-small cell lung cancer (NSCLC), as well as revealed the mutation profiling of NSCLC patients with osimertinib resistance to provide some valuable clues to the mechanisms of resistance., Methods: A total of 317 cancer tissue samples from 317 NSCLC patients at time of progression following osimertinib were submitted to NGS and only 96 tissues were tested by FISH simultaneously. With FISH results as gold standard, enumeration algorithm was applied to establish the optimal model for identifying MET amplification using gene copy number (GCN) data., Results: The optimal model for identifying MET amplification was constructed based on the GCN of MET , BRAF , CDK6 and CYP3A4 , which achieved a 74.0% overall agreement with FISH and performed well in identifying MET amplification except polysomy with a sensitivity of 85.7% and a specificity of 93.9%. The inconsistency between NGS and FISH occurred mainly in polysomy subtype, while MET GCN ≥ 5 could be reliably recognized by NGS. Moreover, the most frequently mutated genes in NSCLC patients with osimertinib resistance were EGFR (59.94%), followed by TP53 (43.85%), NRG1 (9.46%), PIK3CA (6.31%), and ATM (5.36%). The known resistance mechanisms, including MET amplification, EGFR (C797S, L718Q/R), TP53 , CDK4 , CDK6 , CDKN2A , BRAF , KRAS , NRAS and PIK3CA mutations were also disclosed in our cohort., Conclusions: NGS assay can achieve a high concordance with FISH in MET amplification detection and has advantages in portraying various genetic alterations, which is of worthy in clinical promotion., Competing Interests: Author XX, RX, BX, CW, and KZ were employed by the company Shanghai Rightongene Biotechnology Co., Ltd. The remaining 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 Xiao, Xu, Lu, Xin, Wang, Zhu, Zhang and Chen.)

Granulomatous lobular mastitis (GLM) is a chronic idiopathic granulomatous mastitis of the mammary gland characterized by significant pain and a high propensity for recurrence, the incidence rate has gradually increased, and has become a serious breast disease that should not be ignored. GLM is highly suspected relative to microbial infections, especially those of Corynebacterium species; however, the mechanisms involved are unclear, and prevention and treatment are difficult. In this study, we demonstrated the pathogenicity of Corynebacterium parakroppenstedtii in GLM using Koch's postulates. Based on the drug sensitization results of C. parakroppenstedtii, and utilizing a retrospective study in conjunction with a comprehensive literature review, we suggested an efficacious, targeted antibiotic treatment strategy for GLM. Subsequently, we identified the pathogenic factor as a new type of glycolipid (named corynekropbactins) secreted by C. parakroppenstedtii. Corynekropbactins may chelate iron, cause the death of mammary cells and other mammary -gland-colonizing bacteria, and increase the levels of inflammatory cytokines. We further analyzed the prevalence of C. parakroppenstedtii infection in patients with GLM. Finally, we suggested that the lipophilicity of C. parakroppenstedtii may be associated with its infection route and proposed a possible model for the development of GLM. This research holds significant implications for the clinical diagnosis and therapeutic management of GLM, offering new insights into targeted treatment approaches., (© 2024. The Author(s).)

Owing to the extensive use of antibiotics for treating infectious diseases in livestock and humans, the resulting residual antibiotics are a burden to the ecosystem and human health. Hence, for human health and ecological safety, it is critical to determine the residual antibiotics with accuracy and convenience. Graphene-based electrochemical sensors are an effective tool to detect residual antibiotics owing to their advantages, such as, high sensitivity, simplicity, and time efficiency. In this work, we comprehensively summarize the recent advances in graphene-based electrochemical sensors used for detecting antibiotics, including modifiers for electrode fabrication, theoretical elaboration of electrochemical sensing mechanisms, and practical applications of portable electrochemical platforms for the on-site monitoring of antibiotics. It is anticipated that the current review will be a valuable reference for comprehensively comprehending graphene-based electrochemical sensors and further promoting their applications in the fields of healthcare, environmental protection, and food safety.

The Hall effect of topological quantum materials often reveals essential new physics and possesses potential for application. The magnetic Weyl semimetal is one especially interesting example that hosts an interplay between the spontaneous time-reversal symmetry-breaking topology and the external magnetic field. However, it is less known beyond the anomalous Hall effect thereof, which is unable to account for plenty of magnetotransport measurements. We propose a new Hall effect characteristically nonmonotonic with respect to the external field, intrinsic to the three-dimensional Weyl topology, and free from chemical potential fine-tuning. Two related mechanisms from the Landau level bending and chiral Landau level shifting are found, together with their relation to the Shubnikov-de Hass effect. This field-dependent Hall response, universal to thin films and bulk samples, provides a concrete physical picture for existing measurements and is promising to guide future experiments.

The activation of N₂ under mild conditions remains a significant challenge in chemistry. Understanding how the composition of ligands modulates the reactivity of metal centers is pivotal for the rational design of efficient catalysts for nitrogen fixation. Herein, the reactions between polynuclear niobium oxynitride anions Nb 4 N 5-x O x - (x=0-5) and N 2 were investigated by employing mass spectrometry, photoelectron imaging spectroscopy, and theoretical calculations. The rate constants of Nb 4 N 5-x O x - /N 2 gradually decrease for x=0 to x=4, and then increase again for x=5. The sharp increase of the rate constants of Nb 4 O 5 - /N 2 corresponds to a decrease in the electron detachment energy of the Nb 4 O 5 - cluster in the photoelectron spectroscopic experiments. Theoretical calculations suggest that the low-coordinated Nb-Nb sites in Nb 4 N 5-x O x - (x=0-5) behaves as the active centers to bind N 2 in the side-on/end-on manner. Mechanistic analysis reveals that reducing the N/O ratio leads to higher electron densities on the active Nb-Nb centers and decreased positive charge on the metal atoms, which hinders the approach of N 2 to the clusters. This finding discloses fundamental insights into the impact of N/O ratio in fine-tuning the reactivity of metal centers toward N 2 adsorption in related catalytic processes., (© 2024 Wiley-VCH GmbH.)

Animal coloration offers a unique opportunity to explore the evolutionary mechanisms underlying phenotypic diversity. Conspicuous coloration caused by pigments plays a crucial role in social signaling across multiple species by conveying information about individual quality, social ranks, or reproductive condition. Nevertheless, most previous studies have focused predominantly on colors produced by the exogenous pigments-carotenoids. Pterins are another prevalent group of conspicuous pigments, which can be produced endogenously and have received comparatively little attention. Whether pterin-based colors represent reliable signals remains elusive. The remarkable red ventrolateral coloration exhibited by males of the Guinan toad-headed lizard ( Phrynocephalus guinanensis ) in the Mugetan Desert presents an ideal model for investigating pterin-based coloration. Through electron microscopy and metabolomic identification, we discovered three types of pterin pigments within xanthophores. Integrating a series of morphological measurements and behavioral experiments, we found that this red coloration was not correlated with body size, bite force, and testosterone level, nor did females show a preference bias toward it. However, the red intensity predicted male-male competition outcomes, with deeper red males being more likely to emerge as winners. Our results indicated that the pterin-based coloration could convey information about male quality, suggesting its potential role in honest signaling, given the vital importance of pterin metabolism in physiological processes. This study provides a novel case into the understanding of pterin-based colors in animals.

Resistance to gemcitabine in pancreatic ductal adenocarcinoma (PDAC) leads to ineffective chemotherapy and, consequently, delayed treatment, thereby contributing to poor prognosis. Glycolysis is an important intrinsic reason for gemcitabine resistance as it competitively inhibits gemcitabine activity by promoting deoxycytidine triphosphate accumulation in PDAC. However, biomarkers are lacking to determine which patients can benefit significantly from glycolysis inhibition under the treatment of gemcitabine activity, and a comprehensive understanding of the molecular mechanisms that promote glycolysis in PDAC will contribute to the development of a strategy to sensitize gemcitabine chemotherapy. In this study, we aimed to identify a biomarker that can robustly indicate the intrinsic resistance of PDAC to gemcitabine and guide chemotherapy sensitization strategies. After establishing gemcitabine-resistant cell lines in our laboratory and collecting pancreatic cancer and adjacent normal tissues from gemcitabine-treated patients, we observed that circRNA hsa&#95;circ&#95;0008383 (namely cNEK6) was highly expressed in the peripheral blood and tumor tissues of patients and xenografts with gemcitabine-resistant PDAC. cNEK6 enhanced resistance to gemcitabine by promoting glycolysis in PDAC. Specifically, cNEK6 prevented K48 ubiquitination of small ribonucleoprotein peptide A from the BTRC, a ubiquitin E3 ligase; thus, the accumulated SNRPA stopped PP2Ac translation by binding to its G-quadruplexes in 5' UTR of mRNA. mTORC1 pathway was aberrantly phosphorylated and activated owing to the absence of PP2Ac. The expression level of cNEK6 in the peripheral blood and tumor tissues correlated significantly and positively with the activation of the mTORC1 pathway and degree of glycolysis. Hence, the therapeutic effect of gemcitabine is limited in patients with high cNEK6 levels, and in combination with the mTORC1 inhibitor, rapamycin, can enhance sensitivity to gemcitabine chemotherapy., (© 2024. The Author(s).)

We report here a step-economic and cost-effective cross-electrophile coupling of aryl thianthrenium salts with widely available aryl bromides, which proceeded effectively via C-S bond activation at ambient temperature in THF in the presence of a palladium catalyst, magnesium turnings, and lithium chloride to enable the facile assembly of a wide array of structurally diverse biaryls in modest to good yields with good functional group compatibility. In addition, the gram-scale reaction could also be realized.

The role of insects in the agriculture of plants that can rely on wind for successful pollination has been a mystery. We studied the contributions of wind-, insect-, and self-pollination in Castanea henryi (which can receive fruits relying on the wind). The fruit set under open pollination was significantly higher than other treatments. Insects contributed 40% of fruit by their indirect or direct pollination and did not decrease fruit quality. When the stigma was receptive, floral fragrance attracted numerous insects to visit male flowers and carry pollen; however, insects rarely visit female flowers and hardly transport pollen by contacting the stigma. The flower-visiting insects density was positively correlated with air pollen density. Therefore, insects, as facilitators of wind pollination, enhance orchard fruit production. Not emphasizing the importance of wind pollination to chestnut but reminding us that insect management is also extremely important for the agriculture of plants that can be harvested by the wind., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s).)

Direct recycling is considered to be the next-generation recycling technology for spent lithium-ion batteries due to its potential economic benefits and environmental friendliness. For the spent layered oxide cathode materials, an irreversible phase transition to a rock-salt structure near the particle surface impedes the reintercalation of lithium ions, thereby hindering the lithium compensation process from fully restoring composition defects and repairing failed structures. We introduced a transition-metal hydroxide precursor, utilizing its surface catalytic activity produced during annealing to convert the rock-salt structure into a layered structure that provides fast migration pathways for lithium ions. The material repair and synthesis processes share the same heating program, enabling the spent cathode and added precursor to undergo a topological transformation to form the targeted layered oxide. This regenerated material exhibits a performance superior to that of commercial cathodes and maintains 88.4% of its initial capacity after 1000 cycles in a 1.3 Ah pouch cell. Techno-economic analysis highlights the environmental and economic advantages of surface catalytic repair over pyrometallurgical and hydrometallurgical methods, indicating its potential for practical application.

Objective: Training a neural network-based biomedical named entity recognition (BioNER) model usually requires extensive and costly human annotations. While several studies have employed multi-task learning with multiple BioNER datasets to reduce human effort, this approach does not consistently yield performance improvements and may introduce label ambiguity in different biomedical corpora. We aim to tackle those challenges through transfer learning from easily accessible resources with fewer concept overlaps with biomedical datasets., Methods: We proposed GERBERA, a simple-yet-effective method that utilized general-domain NER datasets for training. We performed multi-task learning to train a pre-trained biomedical language model with both the target BioNER dataset and the general-domain dataset. Subsequently, we fine-tuned the models specifically for the BioNER dataset., Results: We systematically evaluated GERBERA on five datasets of eight entity types, collectively consisting of 81,410 instances. Despite using fewer biomedical resources, our models demonstrated superior performance compared to baseline models trained with additional BioNER datasets. Specifically, our models consistently outperformed the baseline models in six out of eight entity types, achieving an average improvement of 0.9% over the best baseline performance across eight entities. Our method was especially effective in amplifying performance on BioNER datasets characterized by limited data, with a 4.7% improvement in F1 scores on the JNLPBA-RNA dataset., Conclusion: This study introduces a new training method that leverages cost-effective general-domain NER datasets to augment BioNER models. This approach significantly improves BioNER model performance, making it a valuable asset for scenarios with scarce or costly biomedical datasets. We make data, codes, and models publicly available via https://github.com/qingyu-qc/bioner&#95;gerbera., 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 Author(s). Published by Elsevier Inc. All rights reserved.)

This study aimed to investigate how aquaporin 1 (AQP1) modulates hypoxia-inducible factor-1α (HIF1α) to promote glycolysis and drive the M1 polarization of macrophages. Within 12 h post-treatment with LPS to induce acute kidney injury in rats, a significant upregulation of AQP1 and HIF1α protein levels was noted in serum and kidney tissues. This elevation corresponded with a decrease in blood glucose concentrations and an enhancement of glycolytic activity relative to the control group. Furthermore, there was a pronounced reduction in the circulating levels of the anti-inflammatory cytokine IL-10, accompanied by an upregulation in the levels of the pro-inflammatory cytokines IL-6 and TNF-α. The administration of an HIF1α inhibitor reversed these effects, which did not affect the production of AQP1 protein. In cellular assays, AQP1 knockdown mitigated the increase in HIF1α expression induced by LPS. Furthermore, the suppression of HIF1α with PX-478 led to decreased expression levels of Hexokinase 2 (HK2) and Lactate Dehydrogenase A (LDHA), indicating that AQP1 regulates glycolysis through HIF1α. M1 polarization of macrophages was reduced by AQP1 knockdown and was further diminished by the addition of an HIF1α inhibitor. Inhibition of the glycolytic process not only weakened M1 polarization but also promoted M2 polarization, thereby reducing the release of inflammatory cytokines. These findings provide a novel perspective for developing therapeutic strategies that target AQP1 and HIF1α, potentially improving the treatment of sepsis-associated AKI., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Non-alcoholic fatty liver disease (NAFLD) is a nutritional and metabolic disease with a high prevalence today. Artemisia capillaris has anti-inflammatory, antioxidant, and other effects. However, the mechanism of A. capillaris in treating NAFLD is still poorly understood., Methods: This study explored the mechanism of A. capillaris in the treatment of NAFLD through network pharmacology and molecular docking, and verified the results through in vivo experiments using a high-fat diet-induced mouse model and in vitro experiments using an oleic acid-induced HepG2 cell model., Key Findings: Aqueous extract of A. capillaris (AEAC) can reduce blood lipids, reduce liver lipid accumulation and liver inflammation in NAFLD mice, and improve NAFLD. Network pharmacology analysis revealed that 51 drug ingredients in A. capillaris correspond to 370 targets that act on NAFLD. GEO data mining obtained 93 liver differentially expressed genes related to NAFLD. In the UHPLC-MS detection results, 36 components were characterized and molecular docked with JNK. Verified in vitro and in vivo, the results show that JNK and the phosphorylation levels of IL-6, IL-1β, c-Jun, c-Fos, and CCL2 are key targets and pathways., Conclusions: This study confirmed that AEAC reduces lipid accumulation and inflammation in the liver of NAFLD mice by inhibiting the JNK/AP-1 pathway., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. 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.)

Purpose: To quantitatively characterize the posterior morphology of high myopia eyes with posterior staphyloma., Methods: Surface points of the eyeball were automatically extracted from magnetic resonance imaging scans using deep learning. Subsequently, the topography of posterior staphylomas was constructed to facilitate accurate visualization and quantification of their location and severity. In the three-dimensional Cartesian coordinate system established with surface points, measurements of distances (D) from each point to the hypothetical pre-elongation eye center within the eyeball and local curvatures (C) at each point on the posterior sclera were computed. Using this data, specific parameters were formulated. The concordance of these parameters with traditional staphyloma classification methods and their association with myopic traction maculopathy (MTM) grades based on the ATN classifications were investigated., Results: The study included 102 eyes from 52 participants. The measured parameters, particularly the variance of distance (Dvar) and the maximum value of the curvature and distance product (C · Dmax), demonstrated efficacy in differentiating various types of posterior staphyloma and exhibited strong correlations with the grades of MTM., Conclusions: The automated generation of the posterior scleral topography facilitated visualization and quantification of staphyloma location and severity. Simple geometric parameters can quantify staphyloma shape and correlate well with retinal complications. Future works on expanding these measures to more imaging modalities could improve their clinical use and deepen insights into the link between posterior staphyloma and related retinal diseases., Translational Relevance: This work has the potential to be translated into clinical practice, allowing for the accurate assessment of staphyloma severity and ultimately improving disease management.

Anterior cruciate ligament (ACL) injury is a common orthopedic disease with a high incidence, long recovery time, and often requiring surgical treatment. However, the susceptibility factors for ACL injury are currently unclear, and there is a lack of analysis on the differences in the ligament itself. Previous studies have focused on germline mutations, with less research on somatic mutations. To determine the role of somatic mutations in ACL injuries, we recruited seven patients between the ages of 20 and 39 years diagnosed with ACL injuries, collected their peripheral blood, injured ligament ends, and healthy ligament ends tissues, and performed exome sequencing with gene function enrichment analysis. We detected multiple gene mutations and gene deletions, which were only present in some of the samples. Unfortunately, it was not possible to determine whether these somatic mutations are related to ligament structure or function, or are involved in ACL injury. However, this study provides valuable clues for future in-depth research., (© 2024. The Author(s).)

Behavioral and clinical studies have revealed a critical role of substance P (SP) in aggression; however, the neural circuit mechanisms underlying SP and aggression remain elusive. Here, we show that tachykinin-expressing neurons in the medial amygdala (MeA Tac1 neurons) are activated during aggressive behaviors in male mice. We identified MeA Tac1 neurons as a key mediator of aggression and found that MeA Tac1 →ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl) projections are critical to the regulation of aggression. Moreover, SP/neurokinin-1 receptor (NK-1R) signaling in the VMHvl modulates aggressive behaviors in male mice. SP/NK-1R signaling regulates aggression by influencing glutamate transmission in neurons in the VMHvl. In summary, these findings place SP as a key node in aggression circuits., (© 2024. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Background: Metabolic-associated fatty liver disease (MAFLD) is a leading cause of chronic liver disease worldwide. Autophagy plays a pivotal role in lipid metabolism; however, the mechanism underlying the reduced autophagic activity in MAFLD remains elusive., Methods: Autophagy was monitored by TUNEL assay and immunofluorescence staining of LC3. The expression of autophagy-related proteins, PPARα, HDAC2, and HRD1 was detected by Western blot. The association between HDAC2 and PPARα promoter was assessed by chromatin immunoprecipitation (ChIP) and dual-luciferase assays, and the HRD1-mediated ubiquitin-proteasomal degradation of HDAC2 was detected by co-immunoprecipitation (co-IP). The in vitro findings were validated in a hypoxia-induced MAFLD mouse model. Histological changes, fibrosis, and apoptosis in liver tissues were detected by hematoxylin and eosin staining, Masson's trichrome staining, and TUNEL assay. The immunoreactivities of key molecules were examined by IHC analysis., Results: Hypoxia-suppressed autophagy in hepatocytes. Hypoxic exposure downregulated HRD1 and PPARα, while upregulating HDAC2 in hepatocytes. Overexpression of PPARα promoted hepatic autophagy, while knocking down HDAC2 or overexpressing HRD1 reduced hypoxia-suppressed autophagy in hepatocytes. Mechanistically, HDAC2 acted as a transcriptional repressor of PPARα, and HRD1 mediated the degradation of HDAC2 through the ubiquitin-proteasome pathway. Functional studies further showed that hypoxia-suppressed hepatic autophagy via the HRD1/HDAC2/PPARα axis in vitro and in vivo., Conclusion: HRD1-mediated ubiquitination of HDAC2 regulates PPARα-mediated autophagy and ameliorates hypoxia-induced MAFLD., 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: Renal sympathetic denervation (RDN) reduces blood pressure (BP)., Methods: This single-arm open-label study enrolled patients with resistant hypertension (RH) and treat them by CT-guided ozone mediated lumbar-renal sympathetic denervation (L-RDN). The primary endpoint was to assess the changes of BP over 24-h ambulatory BP monitoring (ABPM) and to evaluate the anti-hypertensive medication burden (AHMB) at 3-month follow-up. This study was registered in Chictr.org.cn (ChiCTR2300071375)., Results: 17 patients (mean age 65.12 ± 10.77 years) with AHMB of 4.12 ± 1.11 were enrolled. After the procedure, 7 patients (46.7 %) matched the criteria for antihypertensive medication reduction. The AHMB decreased to 3.87 ± 0.96 for the whole objectives and from 3.87 ± 0.96 to 3.55 ± 0.78 for patients with normal baseline renal function. On top of the lessened AHMB, L-RDN further reduced morning systolic BP (SBP) by -8.6 ± 4.0 mmHg (p = 0.034) and diastolic BP (DBP) by -4.6 ± 2.1 mmHg (p = 0.032) for all participants and morning SBP by -13.2 ± 3.6 mmHg (p < 0.001), morning DBP by -6.2 ± 2.4 mmHg (p = 0.011) and daytime SBP by -4.1 ± 1.6 mmHg (p = 0.009) for those with normal baseline renal function at 3-month of follow-up. No adverse events were reported intra- and post operation., Conclusions: CT-guided ozone-mediated L-RDN might be an innovative approach of RDN for treating RH. Confirmatory studies are warranted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aim: The compliance and timeliness of oral laxatives have always been the key factors restricting bowel preparation (BP). We have constructed a novel enhanced-educational content and process based on social software (SS) for BP to optimize these issues., Methods: A multicenter, prospective, randomized controlled study was conducted at 13 hospitals in China from December 2019 to December 2020. A total of 1774 enrollees received standard instructions for BP and were randomly assigned (1:1) to the SS group (SSG) that received a smartphone-based enhanced-education strategy starting 4 h before colonoscopy or the control group (CG)., Results: A total of 3034 consecutive outpatient colonoscopy patients were assessed for eligibility, and 1774 were enrolled and randomly assigned. Ultimately, data from 1747 (SSG vs CG: 875 vs 872) enrollees were collected. The BP adequacy rate was 92.22% (95% CI: 90.46-93.98) in the SSG vs 88.05% (95% CI: 85.91-90.18) in the CG (P = 0.005), and the total Boston Bowel Preparation Scale scores (6.89 ± 1.15 vs 6.67 ± 1.15, P < 0.001) of those in the SSG were significantly higher than those in the CG. The average number of polyps detected in the SSG was considerably higher than that in the CG (0.84 ± 2.00 vs 0.53 ± 1.19, P = 0.037), and the average diameter of the polyps was significantly lower than that of the control group (4.0 ± 2.5 vs 4.9 ± 3.7, P < 0.001)., Conclusions: This SS-enhanced education strategy can improve the BP adequacy rate and increase the average number of polyps detected, especially those of small diameter., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: As the Omicron variant became the dominant coronavirus disease 2019 (COVID-19) strain and the threat to human health decreased, the impact of COVID-19 on male reproductive health and semen quality may have changed. In this prospective observational study, we aimed to investigate the changes in semen quality and sexual function before and after the Omicron variant infection by self-controlled study and to explore the influence of Omicron variant infection on male reproductive health., Methods: We recruited 373 participants who provided semen samples before their first COVID-19 infection. During the subsequent follow-up, only 154 participants provided the second semen samples, 11 of whom were not infected with COVID-19. Sperm quality was assessed approximately 45 and 90 days after COVID-19, as well as before infection., Results: Semen parameters, including total sperm count, total forward sperm, progressive motility, and sperm concentration, significantly declined 45 days after COVID-19 infection. At 90 days after infection, the total sperm count, total forward sperm, and sperm concentration gradually increased to pre-infection levels. Participants who experienced fever showed worse semen quality in terms of total forward sperm, sperm concentration, and sperm progressive rate. However, this phenomenon was not observed in the other group infected with COVID-19 without fever or not infected. In addition, 49 (34.3%) of 143 persons confirmed that the COVID-19 infection resulted in changes in sexual function, with an increase in premature ejaculation diagnostic tool (PEDT) scores., Conclusions: The results of our self-controlled study indicate that COVID-19 is associated with impaired semen quality early after disease onset. After 1-2 spermatogenesis cycles, the semen quality gradually recovers from the infection. These findings are beneficial for better understanding the COVID-19-associated sequelae, which are fundamental for semen collection during assisted reproduction., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-173/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)