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Figainin 2 is a cationic, hydrophobic, α-helical host-defense peptide with 28 residues, which was isolated from the skin secretions of the Chaco tree frog. It shows potent inhibitory activity against both Gram-negative and Gram-positive pathogens and has garnered considerable interest in developing novel classes of natural antibacterial agents. However, as a linear peptide, conformational flexibility and poor proteolytic stability hindered its development as antibacterial agent. To alleviate its susceptibility to proteolytic degradation and improve its antibacterial activity, a series of hydrocarbon-stable analogs of Figainin 2 were synthesized and evaluated for their secondary structure, protease stability, antimicrobial, and hemolytic activities. Among them, F2-12 showed significant improvement in protease resistance and antimicrobial activity compared to that of the template peptide. This study provides a promising strategy for the development of antimicrobial drugs., (© 2024 European Peptide Society and John Wiley & Sons Ltd.)

Evodiamine is a biologically active alkaloid extracted from the fruit of the traditional Chinese medicine Evodia rutaecarpa (Juss.) Benth. (Fructus Evodiae, Wuzhuyu). However, due to its lipophilic chemical structure, low water solubility results in poor bio-availability, which limits its broader application. 3-Amino-10-hydroxyl-evodiamine (E2) was a water-soluble derivative of evodiamine with good anti-tumour bioactivity previously developed by our team; however, its anti-osteoporosis activity remains unclear. This study demonstrates that E2 inhibits the maturation of osteoclasts and bone resorption promoted by receptor activator of nuclear factor-κB ligand (RANKL). Mechanistically, E2 reduced RANKL-induced activation of nuclear factor kappa B (NF-κB) as well as mitogen-activated protein kinase (MAPK) pathways, causing the suppression of the expression of genes associated with osteoclasts in vitro. These genes included nuclear factor of activated T cells c1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), cathepsin k (CTSK) and dendritic cell-specific transmembrane protein (DC-STAMP). Treatment with E2 in vitro resulted in the attenuation of p-ERK, p-JNK, p-p38 and NFATc1 levels. Furthermore, ovariectomized (OVX) mice treated with E2 showed a decrease in osteoclast formation as well as preservation of bone mass. This study concludes with evidence that E2 decreases osteoclast maturation and bone resorption through the regulation of multiple signalling pathways, thereby exhibiting an osteoprotective role in OVX mice. Consequently, E2 exhibits significant potential as a prospective drug candidate for treating osteoporosis., (© 2024 John Wiley & Sons Australia, Ltd.)

Meng Kong,1 Changtong Gao,2 Wenbin Cong,3 Guanghui Li,1 Chuanli Zhou,1 Xuexiao Ma1 1Department of Spine Surgery, Affiliated Hospital of Qingdao University, Qing’dao, Shandong Province, 266000, People’s Republic of China; 2Minimally Invasive Interventional Therapy Center, Qingdao Municipal Hospital, Qing’dao, Shandong Province, 266000, People’s Republic of China; 3Department of Radiology, Affiliated Hospital of Qingdao University, Qing’dao, Shandong Province, 266000, People’s Republic of ChinaCorrespondence: Xuexiao Ma; Chuanli ZhouDepartment of Spine Surgery, Affiliated Hospital of Qingdao University, No. 59, Hai Er Road, Qing’dao, Shandong Province, 266000, People’s Republic of ChinaTel +86 186 61807895Email maxuexiaospinal@163.com; Justin_5257@hotmail.comPurpose: To compare the clinical effects of local anesthesia (LA), general anesthesia (GA) and modified sensation-motion separation anesthesia (MA) in percutaneous endoscopic interlaminar discectomy (PEID) in the treatment of L5/S1 lumbar disc herniation (LDH) for the purpose of guiding junior surgeons.Methods: Eighty-four patients with L5/S1 LDH underwent PEID using three anesthesia methods. Patients in the LA (26), GA (29) and MA (29) groups received a follow-up examination retrospectively. The general parameters, preparation and anesthesia duration, operative duration, recovery time, incidence of complications, ambulation time, length of hospital stay, incidence of severe complications, and reoperation rate were compared, and clinical outcomes were analyzed using a visual analog scale (VAS), the Oswestry Disability Index (ODI), and the Short-Form Health Survey 36 (SF-36).Results: MA demonstrated obvious advantages over the other two methods with respect to operative duration and resulted in a better intraoperative experience than LA. The patients in the MA group required less time in bed postoperatively and shorter hospital stays than those in the GA group. The mean postoperative VAS, ODI and SF-36 scores were significantly better than the preoperative scores in all groups (P< 0.05), but no significant differences in these scores were found among the three groups (P> 0.05). Three cases (3/29) of nervous disorder occurred in the GA group. Two patients (one in the GA group (1/29) and one in the LA (1/26) group) underwent revision surgery, with a total recurrence rate of 2.4% (2/84).Conclusion: Due to its high safety and good tolerance by patients, MA is a suitable method for spinal surgeons who are inexperienced with PEID in the treatment of L5/S1 disc herniation.Keywords: anesthesia, LDH, sensation-motion separation, PEID

Fusarium head blight (FHB), caused by Fusarium graminearum , severely impacts global wheat production, reducing both the yield and quality. In China, fludioxonil, a phenylpyrrole fungicide, is used for managing FHB. This study assessed fludioxonil activity against 120 F. graminearum strains collected from Hubei, Zhejiang, and Jiangsu in 2024, revealing an average EC 50 value of 0.0273 ± 0.0062 μg/mL. We obtained two resistant mutants through chemical taming and discovered a novel point mutation of FgOs1-M460I. Site-directed mutagenesis confirmed that the FgOs1-M460I mutation greatly reduced fludioxonil sensitivity, with an EC 50 value greater than 100 μg/mL. These mutants also displayed reduced sexual and asexual reproduction and lower virulence and accumulated less glycerol under fludioxonil and osmotic stress compared to sensitive strain. The resistant mutants showed no cross-resistance with carbendazim, tebuconazole, phenamacril, pyraclostrobin, or pydiflumetofen. Thus, we conclude that the FgOs1-M460I substitution regulates fludioxonil resistance and plays a role in asexual reproduction, sexual reproduction, and pathogenicity.

Background: Excessive use of antibiotics is a widespread problem. We aim to evaluate the efficacy of a multifaceted intervention for reducing antibiotic use in patients with respiratory tract infections (RTIs)., Methods: In this two-arm cluster randomized controlled trial, we enrolled patients aged 18+ with symptomatic RTIs at 40 township health centers (THCs) selected from 10 counties in Anhui, China. The THCs were randomized using an online tool ('Sealed Envelope') to intervention or usual care (1:1 ratio), stratified by baseline antibiotic prescribing and with random block sizes (4 or 6). The intervention had five components: a half-day clinician training, a WeChat-based peer support group, a decision aid, a poster commitment letter and a patient leaflet. The primary outcome was whether antibiotics were prescribed at the index consultation. Secondary measures included defined daily dose (DDD), illness recovery rate, re-visits to other care-givers or retail pharmacies and incremental cost-effectiveness ratio (ICER). These measures were analyzed using generalized linear mixed modeling controlling for clustering. The study was registered as ISRCTN30652037., Findings: Between December 2021 and September 2022, 1053 patients were recruited (intervention, 21 THCs, n = 552; control, 19 THCs, n = 501), using consecutive sampling. Antibiotic prescribing rate was 55.25% and 66.67% in the intervention and control arms (Odds ratio 0.52, 95% confidence interval [CI]: 0.27, 0.98; p = 0.044). The intervention group also had lower, significant or non-significant, differences for other markers of antibiotic use: DDD (1.57 vs 2.75); prescriptions of two or more types of antibiotics (9.78% vs 11.58%); obtaining antibiotics from retail pharmacies (3.68% vs 5.78) or from other clinics (2.70% vs 4.05%). The intervention resulted in a cost reduction of 9.265 RMB (1.471 USD) per consultation episode and an ICER of -7769.98 RMB or -1233.33 USD/QALYs. The intervention did not encounter any major adverse event., Interpretation: The intervention package was effective and cost-effective in reducing antibiotics prescribing without adverse effects., Funding: The trial was supported by National Natural Science Foundation of China (No. 81861138049) and United Kingdom Research Innovation (No. MR/S013717/1)., Competing Interests: None declared., (© 2024 The Authors.)

Vibrio alfacsensis is traditionally seen as an environmental symbiont within its genus, with no detailedly documented pathogenicity in marine aquaculture to date. This study delves into the largely unexplored pathogenic potential and emerging antibiotic resistance of V. alfacsensis. The VA-1 strain, isolated from recirculating aquaculture system (RAS) effluent of cultured turbot (Scophthalmus maximus), underwent comprehensive analysis including biochemical identification, antibiotic susceptibility testing and reinfection trials. The results confirmed VA-1's pathogenicity and significant multiple antibiotic resistance. VA-1 could induce systemic infection in turbot, with symptoms like kidney enlargement, exhibiting virulence comparable to known Vibrio pathogens, with an LD 50 around 2.36 × 10 6 CFU/fish. VA-1's remarkable resistance phenotype (14/22) suggested potential for genetic exchange and resistance factor acquisition in aquaculture environments. Phylogenetic analysis based on 16S rDNA sequences and whole-genome sequencing has firmly placed VA-1 within the V. alfacsensis clade, while genome-wide analysis highlights its similarity and diversity in relation to strains from across the globe. VA-1 contained numerous replicons, indicating the possibility for the spread of resistance and virulence genes. This study suggests V. alfacsensis may acquire and transfer pathogenic and resistant traits through horizontal gene transfer, a likelihood intensified by changing environmental and aquaculture conditions, highlighting the need for vigilant pathogen monitoring and new non-antibiotic treatments., 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.)

Polyurethane (PU) plays a critical role in elastomers, adhesives, and self-healing materials. We selected the most commonly used aromatic isocyanates, 4,4'-methylene diphenyl diisocyanate (MDI) and tolylene-2,4-diisocyanate (TDI), and the most commonly used aliphatic isocyanates, hexamethylene diisocyanate (HDI), isophorone diisocyanate (IPDI), and dicyclohexylmethane-4,4'-diisocyanate (HMDI), as raw materials, combined with polytetramethylene ether glycol (PTMG) and 1,4-butanediol (BDO) to successfully synthesize five PU materials. The effects of isocyanate structure on polymerization rate, hydrogen bonding, thermal properties, phase separation, wettability, self-healing performance, adhesion, and mechanical properties were systematically investigated. The results show that isocyanates with higher symmetry facilitate hydrogen bonding, but excessive flexibility and crystallinity may inhibit its formation. MDI-based PU exhibits the highest hydrogen bonding index (HBI) of 4.10, along with the most distinct phase separation and the highest tensile strength of 23.4 MPa. HMDI-based PU demonstrates the best adhesion properties, with the highest lap shear strength of 7.9 MPa, and also exhibits excellent scratch healing ability. IPDI-based PU shows good self-healing performance, recovering 88.7% of its original tensile strength and 90.6% of its original lap shear strength after heating at 80 °C for 24 h. Furthermore, all the samples can be reprocessed by melt or solution methods, showing excellent recyclability.

Objective: To culture and expand primary rat aortic vascular stem cells in vitro and evaluate their characteristics as mesenchymal stem cells., Methods: The thoracic and abdominal aortas isolated from 2- to 3-week-old Sprague-Dawley rats were cut into vascular segments 2.0 mm in length and cultured in culture flasks till adhesion and solidification of the outer membranes. The primary cells were further cultured to 80%-90% confluence before passaging. The morphology and growth characteristics of the cells were observed under a microscope, and the expressions of surface marker CD molecules on the cells was analyzed using flow cytometry. Adipogenic and osteogenic differentiation assays were performed to assess the capacity of the cells for multilineage differentiation., Results: After 3 days of culture, a small number of spindle, star-shaped or polygonal cells migrated out from the peripheral of the vascular segments. At 5-6 days, island-like cell clusters occurred and the cells began to proliferate rapidly. The cell clusters expanded radially and showed signs of cell cloning. At 7-8 days, the cells fused into sheets and displayed a vortex-like distribution. The cells in the third passage presented with a uniform morphology, showing a typical fibroblast-like arrangement. Flow cytometry showed that the cells expressed predominantly CD44 (80.3%), CD73 (62.2%) and CD90 (46.8%) with low expressions of CD34 (1.1%), CD45 (0.2%) and CD11b/c (0.2%). Adipogenic and osteogenic differentiation experiments demonstrated that the cells were capable of lipogenic and osteogenic differentiation in vitro ., Conclusion: Rat aortic vascular stem cells with mesenchymal stem cell characteristics can be successfully isolated and cultured by adherent culture of the segmented outer membrane.

Coronary microvascular dysfunction (CMD) represents a principal etiological factor in ischemic heart disease. Nonetheless, a considerable subset of CMD patients experiences diagnostic delays attributable to the inadequacy of current diagnostic methodologies; which in turn results in deferred therapeutic interventions and elevated mortality rates. This study seeks to elucidate the distinct metabolic profile associated with CMD in rat models and to identify specific diagnostic markers that could enhance the diagnostic accuracy for CMD. In this study, 18 Wistar rats were randomly allocated into two groups: the sham group and the CMD group. The CMD group received injections of embolic microspheres into the left ventricle to establish a CMD model. Subsequently, non-targeted metabolomics and acetylated proteomics analyses were conducted. Machine-learning techniques were employed to identify the co-diagnostic markers of the disease. This study identified 53 key proteins through differential expression proteins (DEPs) and modular proteins analysis. Subsequently, four core proteins (Emc1; Ank1; Fbln2; and Hp) were determined as diagnostic markers for CMD using lasso regression, support vector machine, and random forest methodologies. Receiver operating characteristic curve analysis further demonstrated robust diagnostic performance. Gene ontology and kyoto encyclopedia of genes and genome enrichment analyses indicated that the DEPs were predominantly associated with metabolic pathways. Ultimately, the integrative analysis of proteomics and metabolomics suggested that the central metabolic mechanism underlying CMD pathogenesis may be linked to the tricarboxylic acid cycle. This study revealed specific changes in the proteomic and metabolic profiles of CMD rats and identified four diagnostic markers, which are proteins and metabolites that could be potential diagnostic biomarkers for CMD.

THCA (Thyroid carcinoma) is the most common endocrine malignancy in the world. The PLOD1 is highly expressed in THCA, but the mechanism is still unclear. It is found that the cell proliferation and migration were inhibited in si-PLOD1 group, and promoted with PLOD1 overexpression. MAZ is the transcription factor of PLOD1. The cell activities induced MAZ were reversed by si-PLOD1. The Glucose uptake, lactate production and ATP/ADP ratio were decreased with si-PLOD1. The glycolysis related proteins GLUT1, HK2, PFKP, PKM2, LDHA and Wnt/β-catenin pathway proteins WNT5A, cyclin D1, β-catenin were inhibited, GSK-3β is increased in si-PLOD1 group. BML-284 could reversed the si-PLOD1 effects on cell activities and Wnt/β-catenin pathway. The tumor xenografts were inhibited in si-PLOD1 group. As a potential therapeutic target, PLOD1 is regulated by MAZ in THCA. PLOD1 depletion could inhibit THCA cell proliferation and metastasis by glycolysis, which is inhibited by Wnt/β-catenin pathway in THCA., Competing Interests: Declaration of competing interest Mr. Cong declares that he has no conflict of interest. Prof. Liu declares that he has no conflict of interest. Mr. Sun declares that he has no conflict of interest. Mr. Hao declares that he has no conflict of interest. Mr. Gong declares that he has no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Psoriasis is a chronic skin disease characterized by abnormal proliferation and inflammation of epidermal keratinocytes. Fibroblast growth factor 12 (FGF12) is implicated in the regulation of diverse cellular signals; however, its precise mechanism in psoriasis requires further investigation. In this study, high expression of FGF12 is observed in the epidermis of skin lesion in psoriasis patients and imiquimod (IMQ)-induced psoriasis like-dermatitis. Moreover, specific loss of FGF12 in keratinocytes in IMQ-induced psoriasis model alleviates psoriasis-like symptoms and reduces proliferation. In vitro RNA sequencing demonstrates that knockdown of FGF12 effectively arrests the cell cycle, inhibits cell proliferation, and predominantly regulates the p53 signaling pathway. Mechanistically, FGF12 is selectively bound to the RING domain of MDM2, thus partially inhibiting the binding of β-Trcp to MDM2. This interaction inhibits β-Trcp-induced-K48 ubiquitination degradation of MDM2, thereby suppressing the activity of the p53 signaling pathway, which results in excessive cell proliferation. Last, the alleviatory effect of FGF12 deficiency on psoriasis progression is reversed by p53 knockdown. In summary, these findings provide valuable insights into the mechanisms by which FGF12 suppresses p53 signaling in keratinocytes, exacerbating the development of psoriasis. This positive regulatory loop highlights the potential of FGF12 as a therapeutic target to manage psoriasis., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

To improve the durability of the photobioreactor antibiofouling surface for microalgal cultivation, a series of photoreactive poly(2,2,2-trifluoroethyl methacrylate) (PTFEMA) were successfully synthesized and used to modify ethylene-vinyl acetate (EVA) films by a surface coating and UV light grafting method. Fourier transform infrared (FT-IR) spectra, X-ray photoelectron spectroscopy analysis (XPS) and fluorescence microscopy results indicated that PTFEMA were fixed successfully onto the EVA film surface through a covalent bond. During the microalgal adhesion assay, the number of EVA-PTFEMA film-adhered microalgae was 41.4% lower than that of the EVA film. Moreover, the number of microalgae attached to the EVA-PTFEMA film decreased by 61.7% after cleaning, while that of EVA film decreased by only 49.1%. It was found that the contact angle of EVA-PTFEMA film surface increased, and remained stable when immersed in acid and alkali solution for up to 90 days.HIGHLIGHTSDurable photobioreactor antibiofouling surfaces for microalgal cultivation were prepared successfully.The contact angle of antibiofouling coating surface remained stable in acid and base environment for 90 days.The attached microalgae on antibiofouling surface decreased 41.4% than those of unmodified surface.The attached microalgae on antibiofouling surface could be cleaned by 61.7% through changing the flow velocity of microalgal suspension.

Migratory birds play an important role in the cross-regional transmission of zoonotic pathogens. Assessing the presence of zoonotic pathogens carried by migratory birds is critical for disease control. However, information about Blastocystis infection in the migratory birds is very limited. Thus, we conducted this study with the aim to explore the occurrence, prevalence and subtyping of Blastocystis in four breeds of migratory birds in northeastern China. From October 2022 to April 2023, a total of 427 fresh fecal samples were obtained from four breeds of migratory birds in five nature reserves in northeastern China, and screened for Blastocystis by PCR amplification. Twenty-one (4.92 %) of the studied samples were confirmed Blastocystis-positive, and two known zoonotic subtypes ST6 and ST7 were founded, with ST7 being the major subtype. Until now, we firstly reported the infection status and subtyping of Blastocystis in the migratory Greater White-Fronted Goose, White Stork, Oriental White Stork and Bean Goose in China. More importantly, these findings present further data on the genetic diversity and transmission routes of Blastocystis and further arouse public health concerns about this organism., 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.)

Carnivores play key roles in maintaining ecosystem structure and function as well as ecological processes. Understanding how sympatric species coexist in natural ecosystems is a central research topic in community ecology and biodiversity conservation. In this study, we explored intra- and interspecific niche partitioning along spatial, temporal, and dietary niche partitioning between apex carnivores (wolf Canis lupus , snow leopard Panthera uncia , Eurasian lynx Lynx lynx ) and mesocarnivores (Pallas's cat Otocolobus manul , red fox Vulpes vulpes , Tibetan fox Vulpes ferrilata ) in Qilian Mountain National Park, China, using camera trapping data and DNA metabarcoding sequencing data. Our study showed that apex carnivore species had more overlap temporally (coefficients of interspecific overlap ranging from 0.661 to 0.900) or trophically (Pianka's index ranging from 0.458 to 0.892), mesocarnivore species had high dietary overlap with each other (Pianka's index ranging from 0.945 to 0.997), and apex carnivore and mesocarnivore species had high temporal overlap (coefficients of interspecific overlap ranging from 0.497 to 0.855). Large dietary overlap was observed between wolf and snow leopard (Pianka's index = 0.892) and Pallas's cat and Tibetan fox (Pianka's index = 0.997), suggesting the potential for increased resource competition for these species pairs. We concluded that spatial niche partitioning is likely to key driver in facilitating the coexistence of apex carnivore species, while spatial and temporal niche partitioning likely facilitate the coexistence of mesocarnivore species, and spatial and dietary niche partitioning facilitate the coexistence between apex and mesocarnivore species. Our findings consider partitioning across temporal, spatial, and dietary dimensions while examining diverse coexistence patterns of carnivore species in Qilian Mountain National Park, China. These findings will contribute substantially to current understanding of carnivore guilds and effective conservation management in fragile alpine ecosystems., Competing Interests: WC, JL, CH, YL, YZ, LJ, YZ, DL, YX, YZ No competing interests declared, (© 2024, Cong et al.)

Systemic sclerosis is a typical fibrotic disease of unknown etiology that is characterized by abnormal fibroblast activation and excessive deposition of extracellular matrix. Unfortunately, effective therapeutic approaches are lacking. FGF21 plays a key role in mediating a variety of biological activities. However, its specific function in systemic sclerosis is unclear. In this study, we found that the expression of FGF21 was significantly downregulated in fibrotic skin tissue and in TGF-β-stimulated fibroblasts. Furthermore, our studies demonstrated that treatment with recombinant FGF21 in the skin significantly alleviated bleomycin-induced and TBRI-activated fibrosis and inhibited the activation of fibroblasts, whereas skin fibrosis was exacerbated by deletion of FGF21. Mechanistically, FGF21 inhibits the activity of CK2α and promotes the degradation of GLI2. In conclusion, these results indicate that FGF21 attenuates skin fibrosis through the CK2α/GLI2 signaling pathway and therefore may be a potential therapeutic target for systemic sclerosis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

High levels of tumor necrosis factor receptor type II (TNFR2) are preferentially expressed by immunosuppressive CD4 + Foxp3 + regulatory T cells (T regs ), especially those present in the tumor microenvironment, as initially reported by us. There is compelling evidence that targeting TNFR2 markedly enhances antitumor immune responses. Furthermore, a broad spectrum of human cancers also expresses TNFR2, while its expression by normal tissue is very limited. We thus hypothesized that TNFR2 may be harnessed for tumor-targeted delivery of chemotherapeutic agents. In this study, we performed a proof-of-concept study by constructing a TNFR2-targeted PEGylated poly(dl-lactic-co-glycolic acid) (PLGA-PEG) nanodrug delivery system [designated as TNFR2-PLGA-ADR (Adriamycin)]. The results of in vitro study showed that this TNFR2-targeted delivery system had the properties in cellular binding and cytotoxicity toward mouse colon cancer cells. Further, upon intravenous injection, TNFR2-PLGA-ADR could efficiently accumulate in MC38 and CT26 mouse colon tumor tissues and preferentially bind with tumor-infiltrating T regs . Compared with ADR and ISO-PLGA-ADR, the in vivo antitumor effect of TNFR2-PLGA-ADR was markedly enhanced, which was associated with a decrease of TNFR2 + T regs and an increase of IFNγ + CD8 + cytotoxic T lymphocytes in the tumor tissue. Therefore, our results clearly show that targeting TNFR2 is a promising strategy for designing tumor-specific chemoimmunotherapeutic agent delivery system., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Ping Li et al.)

Aims: A myokine secreted by skeletal muscles during exercise called irisin mitigates ischemia-reperfusion (I/R) injury in epithelial cells of various organs by limiting damage to mitochondria. We test whether irisin may preserve the mitochondrial integrity and function in renal tubular epithelial cells and protect against ischemia-reperfusion-induced acute kidney injury (AKI)., Methods: We correlated serum irisin levels with serum creatinine and BUN levels from both AKI patients and healthy individuals. In mice with irisin administration, various renal injury markers such as serum creatinine, BUN, kidney injury molecule-1 (Kim-1), and neutrophil gelatinase-associated lipocalin (NGAL), and renal histopathology were assessed after I/R. To identify the potential mechanisms of the protective of irisin's protective effect, we perfused proximal tubules under confocal microscopy and analyzed kidney tissues by qPCR, western blot, and immunohistochemistry., Results: Serum irisin correlated inversely with serum creatinine and BUN levels were significantly lower in AKI patients than in healthy subjects. Administering irisin to mice after I/R decreased biomarker levels for AKI including serum creatinine, BUN, Kim-1, NAGL and lessened histological changes. In kidney tissues of mice, irisin upregulated the mitochondrial autophagy marker protein microtubule-associated protein 1 light chain 3 (LC3), the mitochondrial autophagy pathway-related proteins PTEN-induced putative kinase 1 (PINK1) and Parkinson's disease 2 parkin (PARK2) and downregulated the reactive substrate protein sequestosome 1 (P62) and mitochondrial membrane proteins translocase of outer mitochondrial membrane 20 (TOM20) and translocase of inner mitochondrial membrane 23 (TIM23)., Conclusion: Irisin protects against renal I/R injury, which may involve the preservation of mitochondrial integrity and function., (© 2024 The Author(s). Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

Terrestrial runoff is a key pathway for the transmission of the terrestrial pathogen Toxoplasma gondii from land to sea, posing a significant threat to marine ecosystems. Understanding the mechanisms by which T. gondii is transported from terrestrial to marine environment is crucial for developing effective prevention and control strategies for toxoplasmosis in marine organisms. This study investigates the transport of T. gondii through terrestrial runoff in the Sow River, a representative watershed in Weihai, China. Surface water, bottom water and sediment samples were collected and analyzed for T. gondii DNA using PCR methods. Out of 5328 samples, the prevalence of T. gondii was found to be 8.61 % in surface water, 9.80 % in bottom water and 16.61 % in sediment, with sediment identified as a significant reservoir. Additionally, estuarine zones showed a higher prevalence of T. gondii (16.80 %) compared to riverine areas (9.00 %). The study further revealed that seasonal climate variations, such as temperature and precipitation, had no significant impact on the distribution of T. gondii. However, there was significant spatial variability, with estuarine conditions facilitating increased pathogen transmission. These findings highlight the importance of estuaries and sediments as key conduits for T. gondii entry in marine food webs. The results provide a theoretical basis for designing infection prevention and control strategies aimed at protecting marine 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 B.V. All rights reserved.)

Objectives: The aim of this study was to investigate the efficacy of three-dimensional (3D) printing-assisted treatment for acetabular fractures (AFs) and to compare with conventional surgical methods., Patients and Methods: Between May 2019 and May 2022, a total of 44 patients (33 males, 11 females; mean age: 40.6±11.8 years; range, 20 to 68 years) who were diagnosed with AFs based on clinical symptoms, X-ray and computed tomography (CT) and underwent open reduction and internal fixation in Hospital of Xinjiang Production and Construction Corps were retrospectively analyzed. The patients were divided into two groups based on whether 3D printing was applied as the experimental group (n=24) and control group (n=20). In the experimental group, pelvic and acetabular data were imported into a 3D printer, and an equal-scale highly simulated model was printed using photosensitive resin as the 3D printing material. The model was used to develop more specific personalized surgical plans, to determine the optimal sequence of surgical procedures for fracture reduction, and simulate surgery in vitro., Results: In the experimental group, the mean surgical duration was shorter (123.57±22.05 vs. 163.57±26.20 min, p<0.001), the mean intraoperative bleeding loss was lower (557.14±174.15 vs. 885.71±203.27 mL, p<0.001), and the frequency of intraoperative fluoroscopy was lower (8.64±1.65 vs. 12.07±2.76, p<0.001) than in the control group. No statistically significant differences were found between the two groups in the Visual Analog Scale scores after surgery or the hip function score after treatment (p>0.05). No major postoperative complications were observed in any of the patients., Conclusion: Compared to conventional surgical treatment, preoperative 3D printing-assisted treatment for adult patients with AFs can significantly reduce surgical duration, intraoperative bleeding loss and frequency of intraoperative C-arm fluoroscopy, reducing surgical difficulty and improving surgical safety.

Gram-positive S. aureus is one of the leading pathogens for death associated with antimicrobial resistance. The β-lactamase (Bla) secreted by methicillin-resistant S. aureus (MRSA) hydrolyzes nearly all β-lactam antibiotics, leaving only a few antibiotics available for the clinical treatment of MRSA infections. Thereby, a Bla-responsive peptide (BLAP) is designed here with the capacity of inhibiting MRSA infection through mimicking the host defense mechanism of human defensin-6. The BLAP comprising a self-assembling peptide sequence can respond specifically to the secreted Bla and assemble in situ surrounding MRSA. The assembled nanofibrous network is able to trap MRSA, preventing its invasion into the host cells effectively. As a consequence, the intramuscular injection of BLAP significantly restricted bacterial infection and abscess formation in mice. The biomimetic BLAP holds great potential for the efficient treatment of drug-resistant gram-positive bacterial infections., (© 2024 Wiley‐VCH GmbH.)

Lenvatinib is a commonly used first-line drug for the treatment of advanced hepatocellular carcinoma (HCC). However, its clinical efficacy is limited due to the drug resistance. EVA1A was a newly identified tumor suppressor, nevertheless, the impact of EVA1A on resistance to lenvatinib treatment in HCC and the potential molecular mechanisms remain unknown. In this study, the expression of EVA1A in HCC lenvatinib-resistant cells is decreased and its low expression was associated with a poor prognosis of HCC. Overexpression of EVA1A reversed lenvatinib resistance in vitro and in vivo, as demonstrated by its ability to promote cell apoptosis and inhibit cell proliferation, invasion, migration, EMT, and tumor growth. Silencing EVA1A in lenvatinib-sensitive parental HCC cells exerted the opposite effect and induced resistance to lenvatinib. Mechanistically, upregulated EVA1A inhibited the PI3K/AKT/MDM2 signaling pathway, resulting in a reduced interaction between MDM2 and p53, thereby stabilizing p53 and enhancing its antitumor activity. In addition, upregulated EVA1A suppressed the PI3K/AKT/mTOR signaling pathway and promoted autophagy, leading to the degradation of mutant p53 and attenuating its oncogenic impact. On the contrary, loss of EVA1A activated the PI3K/AKT/MDM2 signaling pathway and inhibited autophagy, promoting p53 proteasomal degradation and mutant p53 accumulation respectively. These findings establish a crucial role of EVA1A loss in driving lenvatinib resistance involving a mechanism of modulating PI3K/AKT/p53 signaling axis and suggest that upregulating EVA1A is a promising therapeutic strategy for alleviating resistance to lenvatinib, thereby improving the efficacy of HCC treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alzheimer's disease (AD) poses a significant burden on the economy and healthcare systems worldwide. Although the pathophysiology of AD remains debatable, its progression is strongly correlated with the accumulation of tau aggregates. Therefore, tau clearance from brain lesions can be a promising strategy for AD therapy. To achieve this, the present study combined proteolysis-targeting chimera (PROTAC), a novel protein-degradation technique that mediates degradation of target proteins via the ubiquitin-proteasome system, and a neurotransmitter-derived lipidoid (NT-lipidoid) nanoparticle delivery system with high blood-brain barrier-penetration activity, to generate a novel nanomedicine named NPD. Peptide 1, a cationic tau-targeting PROTAC is loaded onto the positively charged nanoparticles using DNA-intercalation technology. The resulting nanomedicine displayed good encapsulation efficiency, serum stability, drug release profile, and blood-brain barrier-penetration capability. Furthermore, NPD potently induced tau clearance in both cultured neuronal cells and the brains of AD mice. Moreover, intravenous injection of NPD led to a significant improvement in the cognitive function of the AD mice, without any remarkable abnormalities, thereby supporting its clinical development. Collectively, the novel nanomedicine developed in this study may serve as an innovative strategy for AD therapy, since it effectively and specifically induces tau protein clearance in brain lesions, which in turn enhances cognition., (© 2024 Wiley‐VCH GmbH.)

Osteoporosis, a global bone disease, results in decreased bone density, mass, and microarchitecture deterioration, increasing fracture risk. In previous research, FRATtide, a peptide derived from a glycogen synthase kinase-3 binding protein, effectively hindered osteoclast differentiation to yield therapeutically potent derivatives via single and double stapling. However, FRATtide's structure-activity relationship remains unclear. This study synthesized 25 FRATtide-derived peptides through systematic alanine scanning and evaluated their activities. Substitutions in Pro 2 , Leu 5 , Leu 9 , Val 10 , Leu 11 , Ser 12, Asn 14 , Leu 15 , Ile 16 , Glu 18 , Arg 22 , Ser 25 , and Arg 26 showed reduced activity, while FRT13 and FRT20 with Gly 13 and Arg 21 substitutions, respectively, displayed enhanced activities. F-actin binding and bone resorption assays on FRT13 and FRT20 showed better inhibition of osteoclast differentiation and bone resorption compared with FRATtide. This study elucidated FRATtide's structure-activity relationship, thereby facilitating future structural optimization for osteoporosis treatment., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Bile acid homeostasis is critical to human health. Low-level exposure to antibiotics has been suggested to potentially disrupt bile acid homeostasis by affecting gut microbiota, but relevant data are still lacking in humans, especially for the level below human safety threshold. We conducted a cross-sectional study in 4247 Chinese adults by measuring 34 parent antibiotics and their metabolites from six common categories (i.e., tetracyclines, qinolones, macrolides, sulfonamides, phenicols, and lincosamides) and ten representative bile acids in fasting morning urine using liquid chromatography coupled to mass spectrometry. Daily exposure dose of antibiotics was estimated from urinary concentrations of parent antibiotics and their metabolites. Urinary bile acids and their ratios were used to reflect bile acid homeostasis. The estimated daily exposure doses (EDED) of five antibiotic categories with a high detection frequency (i.e., tetracyclines, qinolones, macrolides, sulfonamides, and phenicols) were significantly associated with urinary concentrations of bile acids and decreased bile acid ratios in all adults and the subset of 3898 adults with a cumulative ratio of antibiotic EDED to human safety threshold of less than one. Compared to a negative detection of antibiotics, the lowest EDED quartiles of five antibiotic categories and four individual antibiotics with a high detection frequency (i.e., ciprofloxacin, ofloxacin, trimethoprim, and florfenicol) in the adults with a positive detection of antibiotics had a decrease of bile acid ratio between 6.6% and 76.6%. Except for macrolides (1.2×10 2 ng/kg/day), the medians of the lowest EDED quartile of antibiotic categories and individual antibiotics ranged from 0.32 ng/kg/day to 10 ng/kg/day, which were well below human safety thresholds. These results suggested that low-level antibiotic exposure could disrupt bile acid homeostasis in adults and existing human safety thresholds may be inadequate in safeguarding against the potential adverse health effects of low-level exposure to antibiotics., 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: The prescribing of antibiotics to treat COVID-19 patients has been observed to occur frequently, often without clear justification. This trend raises concerns that it may have exacerbated antimicrobial resistance (AMR). Despite longstanding concerns over AMR in Southeast Asian countries, data on this issue are notably lacking., Objectives: To explore the impact of COVID-19 on antibiotic prescribing, bacterial infection prevalence and common resistant pathogens in COVID-19 inpatients., Methods: We searched PubMed, EMBASE, Web of Science and ThaiJO (a Thai academic database) to identify studies conducted in ASEAN member countries and published between December 2019 and March 2023. Screening and data extraction were done by two independent reviewers, with results synthesized using random-effects meta-analyses and descriptive statistical analyses. This review was registered with PROSPERO (CRD42023454337)., Results: Of the 29 studies (19 750 confirmed COVID-19 cases) included for final analysis, the antibiotic prescribing rate was 62.0% (95%CI: 46.0%-76.0%) with a prescribing rate of 58.0% (21.0%-91.0%) in mild/moderate cases versus 91.0% (82.0%-98.0%) in severe/critical cases. Notably, 80.5% of antibiotics prescribed fall under the WHO AWaRe 'Watch' list, followed by 'Access' at 18.4% and 'Reserve' at 1.0%. The reported bacterial infection prevalence was 16.0% (7.0%-29.0%), with Acinetobacter baumannii being the most common resistant bacterium at 7.7%. Singapore was notable for its lower antibiotic prescribing rate of 17.0% and a lower bacterial infection rate of 10.0%., Conclusions: High antibiotic prescribing rates, disproportionate to bacterial infections and varying practices for COVID-19 inpatients across countries highlight the urgent need for this region to collaborate to tackle and mitigate AMR., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Endoscopic surgery is an effective and common clinical practice for chronic sinusitis. Nasal packing materials are applied in nasal surgery to prevent hemorrhage and promote wound healing. In this study, a degradable polyurethane foam dressing is successfully developed as a promising nasal packing material with good biocompatibility and antibacterial capability. Specifically, quaternized chitosan (QCS) serves as the crosslinker instead of polyols to offer polyurethane foam (PUF-QCS) antibacterial capability. The PUF-QCS2.0 % (with 2.0 wt% QCS) exhibits satisfactory liquid absorption capacity (19.4 g/g), high compressive strengths at both wet (14.5 kPa) and dry states (7.7 kPa), and a good degradation rate (8.3 %) within 7 days. Meanwhile, PUF-QCS2.0 % retains long-term antibacterial activity for 7 days and kills 97.3 % of S. aureus and 91.8 % of E. coli within 6 hours in antibacterial testing. Furthermore, PUF-QCS2.0 % demonstrates a positive hemostatic response in the rabbit nasal septum mucosa trauma model by reducing hemostatic time over 50.0 % and decreasing blood loss up to 76.1 % compared to the commercial PVA nasal packing sponge. Importantly, PUF-QCS also exhibits a significant antibacterial activity in nasal cavity. This nasal packing material has advantages in post-surgery bleeding control and infection prevention. STATEMENT OF SIGNIFICANCE: The performance of a nasal packing sponge requires good mechanical properties, fast and high liquid absorption rate, effective degradability and strong antibacterial activity. These features are helpful for improving the postoperative recovery and patient healing. However, integrating these into a single polyurethane foam is a challenge. In this study, quaternized chitosan (QCS) is synthesized and used as a chain extender and antibacterial agent in preparing a degradable polyurethane foam (PUF-QCS) dressing. PUF-QCS undergoes partial degradation and exhibits effective broad-spectrum antibacterial activity in 7 days. The reduction of postoperative bleeding and infection observed in the animal experiment further demonstrates that the PUF-QCS developed here outperforms the existing commercial nasal packing materials., 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 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Schizophrenia (SCZ) is a type of psychiatric disorder characterized by multiple symptoms. Our aim is to decipher the relevant mechanisms of immune-related gene signatures in SCZ., Methods: The SCZ dataset and its associated immunoregulatory genes were retrieved using Gene Expression Omnibus (GEO) and single-sample gene set enrichment analysis (ssGSEA). Co-expressed gene modules were determined through weighted gene correlation network analysis (WGCNA). To elucidate the functional characteristics of these clusters, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used. Additionally, gene set enrichment analysis (GSEA) and Gene Set Variation Analysis (GSVA) were conducted to identify enriched pathways for the immune subgroups. A protein-protein interaction (PPI) network analysis was performed to identify core genes relevant to SCZ., Results: A significantly higher immune score was observed in SCZ compared to control samples. Seven distinct gene modules were identified, with genes highlighted in green selected for further analysis. Using the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) method, degrees of immune cell adhesion and accumulation related to 22 different immune cell types were calculated. Significantly enriched bioprocesses concerning the immunoregulatory genes with differential expressions included interferon-beta, IgG binding, and response to interferon-gamma, according to GO and KEGG analyses. Eleven hub genes related to immune infiltration emerged as key players among the three top-ranked GO terms., Conclusions: This study underscores the involvement of immunoregulatory reactions in SCZ development. Eleven immune-related genes (IFITM1 (interferon induced transmembrane protein 1), GBP1 (guanylate binding protein 1), BST2 (bone marrow stromal cell antigen 2), IFITM3 (interferon induced transmembrane protein 3), GBP2 (guanylate binding protein 2), CD44 (CD44 molecule), FCER1G (Fc epsilon receptor Ig), HLA-DRA (major histocompatibility complex, class II, DR alpha), FCGR2A (Fc gamma receptor IIa), IFI16 (interferon gamma inducible protein 16), and FCGR3B (Fc gamma receptor IIIb)) were identified as hub genes, representing potential biomarkers and therapeutic targets associated with the immune response in SCZ patients.

Ameson portunus is an intracellular pathogen that infects marine crabs Portunus trituberculatus and Scylla paramamosain, causing significant economic losses. However, research into this important parasite has been limited due to the absence of an in vitro culture system. To address this challenge, we developed an in vitro cultivation model of A. portunus using RK13 cell line in this study. The fluorescent labeling assay indicated a high infection rate (∼60 %) on the first day post-infection and quantitative PCR (qPCR) detection demonstrated successful infection as early as six hours post-inoculation. Fluorescence in situ hybridization (FISH) and qPCR were used for the detection of A. portunus infected cells. The FISH probe we designed allowed detection of A. portunus in infected cells and qPCR assay provided accurate quantification of A. portunus in the samples. Transmission electron microscopy (TEM) images revealed that A. portunus could complete its entire life cycle and produce mature spores in RK13 cells. Additionally, we have identified novel life cycle characteristics during the development of A. portunus in RK 13 cells using TEM. These findings contribute to our understanding of new life cycle pathways of A. portunus. The establishment of an in vitro culture model for A. portunus is critical as it provides a valuable tool for understanding the molecular and immunological events that occur during infection. Furthermore, it will facilitate the development of effective treatment strategies for this intracellular pathogen., 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.)

Yuan Q, Han J, Cong W, et al. Int J Nanomed. 2014;9(1):4829– 4846.The authors of this article have advised that there is an error in Figure 2A of this published paper. The representative photo of flow cytometry profile of 10 nM DSN treated cells is the same as 1 nM DSN treated cells. This is incorrect and this error was introduced during the editing process by Dovepress.Read the original article

Alzheimer's disease (AD) becomes one of the main global burden diseases with the aging population. This study was to investigate the potential molecular mechanisms of rapidly accelerated fibrosarcoma-1 (RAF-1) in AD through bioinformatics analysis. Differential gene expression analysis was performed in GSE132903 dataset. We used weight gene correlation network analysis (WGCNA) to evaluate the relations among co-expression modules and construct global regulatory network. Cross-talking pathways of RAF-1 in AD were identified by functional enrichment analysis. Totally, 2700 differentially expressed genes (DEGs) were selected between AD versus non-dementia control and RAF-1-high versus low group. Among them, DEGs in turquoise module strongly associated with AD and high expression of RAF-1 were enriched in vascular endothelial growth factor (VEGF), neurotrophin, mitogen-activated protein kinase (MAPK) signaling pathway, oxidative phosphorylation, GABAergic synapse, and axon guidance. Moreover, cross-talking pathways of RAF-1, including MAPK, VEGF, neurotrophin signaling pathways, and axon guidance, were identified by global regulatory network. The performance evaluation of AUC was 84.2%. The gene set enrichment analysis (GSEA) indicated that oxidative phosphorylation and synapse-related biological processes were enriched in RAF-1-high and AD group. Our findings strengthened the potential roles of high RAF-1 level in AD pathogenesis, which were mediated by MAPK, VEGF, neurotrophin signaling pathways, and axon guidance., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Sepsis, a systemic immune syndrome caused by severe trauma or infection, poses a substantial threat to the health of patients worldwide. The progression of sepsis is heavily influenced by septic liver injury, which is triggered by infection and cytokine storms, and has a significant impact on the tolerance and prognosis of septic patients. The objective of our study is to elucidate the biological role and molecular mechanism of fibroblast growth factor 21 (FGF21) in the process of sepsis., Objectives: This study was undertaken in an attempt to elucidate the function and molecular mechanism of FGF21 in therapy of sepsis., Methods: Serum concentrations of FGF21 were measured in sepsis patients and septic mice. Liver injury was compared between mice FGF21 knockout (KO) mice and wildtype (WT) mice. To assess the therapeutic potential, recombinant human FGF21 was administered to septic mice. Furthermore, the molecular mechanism of FGF21 was investigated in mice with myeloid-cell specific HIF-1α overexpression mice (LyzM-Cre DIO-HIF-1α ) and myeloid-cell specific Atg7 knockout mice (Atg7 △mye )., Results: Serum level of FGF21 was significantly increased in sepsis patients and septic mice. Through the use of recombinant human FGF21 (rhFGF21) and FGF21 KO mice, we found that FGF21 mitigated septic liver injury by inhibiting the initiation and propagation of inflammation. Treatment with rhFGF21 effectively suppressed the activation of proinflammatory macrophages by promoting macroautophagy/autophagy degradation of hypoxia-inducible factor-1α (HIF-1α). Importantly, the therapeutic effect of rhFGF21 against septic liver injury was nullified in LyzM-Cre DIO-HIF-1α mice and Atg7 △mye mice., Conclusions: Our findings demonstrate that FGF21 considerably suppresses inflammation upon septic liver injury through the autophagy/ HIF-1α axis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Production and hosting by Elsevier B.V.)

Vascular aging (VA) is recognized as a pivotal factor in the development and progression of atherosclerosis (AS). Although various epidemiological and clinical research has demonstrated an intimate connection between aging and AS, the candidate mechanisms still require thorough examination. This review adopts an aging-centric perspective to deepen the comprehension of the intricate relationship between biological aging, vascular cell senescence, and AS. Various aging-related physiological factors influence the physical system's reactions, including oxygen radicals, inflammation, lipids, angiotensin II, mechanical forces, glucose levels, and insulin resistance. These factors cause endothelial dysfunction, barrier damage, sclerosis, and inflammation for VA and promote AS via distinct or shared pathways. Furthermore, the increase of senescent cells inside the vascular tissues, caused by genetic damage, dysregulation, secretome changes, and epigenetic modifications, might be the primary cause of VA.

Toxoplasma gondii infection in wild marine mammals is a growing problem and is associated with adverse impacts on marine animal and public health. This systematic review, meta-analysis and meta-regression estimates the global prevalence of T. gondii infection in wild marine mammals and analyses the association between T. gondii infection and epidemiological variables. PubMed, Web of Science, Science Direct, China National Knowledge Infrastructure, and Wanfang Data databases were searched until 30 May 2021. Eighty-four studies (n = 14,931 wild marine mammals from 15 families) were identified from literature. The overall pooled prevalence of T. gondii infection was 22.44% [3848/14,931; 95% confidence interval (CI): 17.29-28.04]. The prevalence in adult animals 21.88% (798/3119; 95% CI: 13.40-31.59) was higher than in the younger age groups. North America had a higher prevalence 29.92% (2756/9243; 95% CI: 21.77-38.77) compared with other continents. At the country level, the highest prevalence was found in Spain 44.26% (19/88; 95%CI: 5.21-88.54). Regarding climatic variables, the highest prevalence was found in areas with a mean annual temperature >20°C 36.28% (171/562; 95% CI: 6.36-73.61) and areas with an annual precipitation > 800 mm 26.92% (1341/5042; 95% CI: 18.20-36.59). The subgroup and meta-regression analyses showed that study-level covariates, including age, country, continent, and mean temperature, partly explained the between-study heterogeneity. Further studies are needed to investigate the source of terrestrial to aquatic dissemination of T. gondii oocysts, the fate of this parasite in marine habitat and its effects on wild marine mammals., (© 2022 Wiley-VCH GmbH.)

The application of probiotics, in aquaculture, is becoming increasingly widespread and have had positive application effects. However, reports of loach-derived probiotics are quite limited. In this study, two representative strains of lactic acid bacteria with excellent traits, namely, Weissella confusa N17 and Lactobacillus saniviri N19, were screened from the intestine of healthy loaches. W. confusa N17 and L. saniviri N19 could inhibit different common various pathogenic bacteria, especially Aeromonas spp., and were sensitive to the most common antibiotics. The survival rate of the two strains exceeded 50% after 4 h of incubation in 10% loach bile. Moreover, the two strains showed significant tolerance to trypsin. Their autoaggregation capacity and hydrophobicity were greater than 30%. In addition, the aggregation ability of both strains was higher than 30% for both A. veronii TH0426 and A. hydrophila TPS. The two strains had a high biofilm-forming ability and strong adhesion to epithelioma papulosum cyprini (EPC) cells. Scanning electron microscopy results showed that the culture supernatants of the two strains had a significantly destructive effect on A. veronii TH0426 and A. hydrophila TPS. Overall, the traits of W. confusa N17 were better than those of L. saniviri N19. Genome sequencing and analysis demonstrated a lack of virulence factor-related or drug resistance-related genes in genome N17. The diet supplemented with the W. confusa N17 strain significantly improved the resistance of loaches to A. veronii infection, and the protection rate reached 57.1%. Therefore, W. confusa N17 exhibits promising for further applications in loach aquaculture., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Heterosis is widely used in crop production, but phenotypic dominance and its underlying causes in soybeans, a significant grain and oil crop, remain a crucial yet unexplored issue. Here, the phenotypes and transcriptome profiles of three inbred lines and their resulting F 1 seedlings were analyzed. The results suggest that F 1 seedlings with superior heterosis in leaf size and biomass exhibited a more extensive recompilation in their transcriptional network and activated a greater number of genes compared to the parental lines. Furthermore, the transcriptional reprogramming observed in the four hybrid combinations was primarily non-additive, with dominant effects being more prevalent. Enrichment analysis of sets of differentially expressed genes, coupled with a weighted gene co-expression network analysis, has shown that the emergence of heterosis in seedlings can be attributed to genes related to circadian rhythms, photosynthesis, and starch synthesis. In addition, we combined DNA methylation data from previous immature seeds and observed similar recompilation patterns between DNA methylation and gene expression. We also found significant correlations between methylation levels of gene region and gene expression levels, as well as the discovery of 12 hub genes that shared or conflicted with their remodeling patterns. This suggests that DNA methylation in contemporary hybrid seeds have an impact on both the F 1 seedling phenotype and gene expression to some extent. In conclusion, our study provides valuable insights into the molecular mechanisms of heterosis in soybean seedlings and its practical implications for selecting superior soybean varieties., 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, Chen, Deng, Zhao, Yao, Li, Cong, Zang, Zhao, Zhang, Yang and Zhang.)

Skin wound healing is a complex and organized biological process, and the dermal fibroblasts play a crucial role. α-Catenin is known to be involved in regulating various cellular signals, and its role in wound healing remains unclear. Here, we have identified the pivotal role of the α-catenin/FAK/YAP signaling axis in the proliferation and migration of dermal fibroblasts, which contributes to the process of skin wound healing. Briefly, when α-catenin was knocked down specifically in dermal fibroblasts, the wound healing rate is significantly delayed. Moreover, interfering with α-catenin can impede the proliferation and migration of dermal fibroblasts both in vitro and in vivo. Mechanistically, the overexpression of α-catenin upregulates the nuclear accumulation of YAP and transcription of downstream target genes, resulting in enhanced the proliferation and migration of dermal fibroblasts. Furthermore, the FAK Tyr397 phosphorylation inhibitor blocked the promoting effects of α-catenin on YAP activation. Importantly, the continuous phosphorylation mutation of FAK Tyr397 reversed the retardatory effects of α-catenin knockdown on wound healing, by increasing the vitality of fibroblasts. Likewise, α-catenin/FAK was validated as a therapeutic target for wound healing in the db/db chronic trauma model. In summary, our findings have revealed a novel mechanism by which α-catenin facilitates the function of fibroblasts through the activity of the FAK/YAP signaling axis. These findings define a promising therapeutic strategy for accelerating the wound healing process., (© 2024 Federation of American Societies for Experimental Biology.)

The co-pelletization of microalgae with filamentous fungi was a promising approach for microalgae harvest. However, the real conditions of microalgae growth limited the arbitrary optimization of co-pellets formation with filamentous fungi. Therefore, it is urgent to develop an approach to manipulate the co-pelletization through treatment of A. niger spores. In this study, Aspergillus niger and Chlorella vulgaris were used as the model species of filamentous fungi and microalgae to investigate co-pellets formation using A. niger spores after by different pH solutions treatment, swelling, snailase treatment. The importance of spore treatments on C. vulgaris harvest in sequence was claimed based on response surface methodology analysis. The pH solutions treatment, swelling, snailase treatment of A. niger spore contributed 21.0%, 10.5%, 40.7% of harvest ratio of C. vulgaris respectively, which guided the application of spore treatment into co-pelletization. Treatment of spore was showed as an efficient approach to manipulate co-pelletization for microalgae harvest in diverse microalgae condition. This results promoted the application of co-pelletization technology in microalgae harvest of various conditions., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Ethnopharmacological Relevance: Cardiovascular disease (CVD) and fatigue are two common diseases endangering human life and health that may interact and reinforce one another. Myocardial infarction survivors frequently experience fatigue, and acute myocardial infarction (AMI) is one of the most common cardiovascular diseases that cause fatigue-induced sudden death. Sheng Mai Yin (SMY), a Chinese medicine prescription, is traditionally used for the treatment of diabetes and cardiovascular disease, and has been demonstrated to reduce fatigue and safeguard cardiac function., Aim of the Study: This study aims to investigate the effects and underlying mechanisms of SMY in treating fatigue and AMI., Materials and Methods: The pharmacological mechanisms of SMY in treating fatigue and AMI were predicted by bioinformatics and network pharmacology methods. After administering SMY at high, medium and low doses, the swimming time to exhaustion, hemoglobin level, serological parameters and hypoxia tolerance time were detected in C57BL/6N mice, and the left ventricular ejection fractions (LVEF), left ventricular fractional shortening (LVFS), grasp strength, cardiac histopathology, serological parameters and the expression of PINK1 and Parkin proteins were examined in Wistar rats., Results: 371 core targets for SMY and 282 disease targets for fatigue and AMI were obtained using bioinformatics and network pharmacology methods. Enrichment analysis of target genes revealed that SMY might interfere with fatigue and AMI through biological processes such as mitochondrial autophagy, apoptosis, and oxidative stress. For in vivo experiments, SMY showed significant anti-fatigue and hypoxia tolerance effects in mice; It also improved the cardiac function and grasp strength, decreased their cardiac index, myocardial injury and fibrosis degree, and induced serological parameters levels and the expression of PTEN-induced putative kinase 1 (PINK1) and Parkin proteins in myocardium, suggesting that SMY may exert cardioprotective effects in a joint rat model of fatigue and AMI by inhibiting excessive mitochondrial autophagy., Conclusion: This study revealed the anti-fatigue, anti-hypoxia and cardioprotective effects of SMY in a joint model of fatigue-AMI, and the pharmacological mechanism may be related to the inhibition of mitochondrial autophagy in cardiomyocytes through the PINK1/Parkin pathway. The discoveries may provide new ideas for the mechanism study of traditional Chinese medicine, especially complex prescriptions, in treating fatigue and AMI., 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 © 2023. Published by Elsevier B.V.)

In spite of effective antiosteoporosis potency, teriparatide, a bone-building agent approved by the FDA (Food and Drug Administration), was proven to exhibit various side effects. In our previous work, we developed a universal strategy for synthesizing arginine N -glycosylated peptides termed silver-promoted solid-phase glycosylation (SSG) strategy. However, it is unknown whether the SSG strategy can be applied in the peptide drug design. Herein, we first reported the optimization of teriparatide via SSG strategy. Using Arg20 and/or Arg25 as the modifying positions, three series of arginine N -glycosylated teriparatide analogs were successfully synthesized, of which the introduced sugar groups included glucose, galactose, mannose, rhamnose, ribose, 2-acetamino-2-deoxy-glucose, xylose, lactose, and maltose. Among the 27 arginine N -glycosylated derivatives, Arg20-xylose and Arg25-maltose teriparatide analogs, termed PTH-1g and PTH-2i , respectively, indicated enhanced serum stability and significantly improved antiosteoporotic activities in vitro and in vivo compared with the native counterpart. They may serve as effective therapeutic candidates for treating osteoporosis.

Ammonium dinitramide (NH 4 N(NO 3 ) 2 , ADN) is regarded as a promising oxidizer due to its low signature and high specific impulse. Generally, ADN undergoes exothermic decomposition above 140 °C accompanied by the byproduct of ammonium nitrate (AN). The inevitable endothermic decomposition of AN decreases the overall heat release, and so there is a need to develop efficient catalysts to guide ADN decomposition along desired pathways with a lower decomposition temperature and higher heat release. A suitable catalyst should be able to withstand the harsh conditions in a thruster to achieve a stable thrust force, which poses a huge obstacle for manufacturing a stable and active catalyst. This review gives a comprehensive summary of the thermal and catalytic decomposition pathways of ADN for the first time, which is expected to deepen the understanding of its reaction mechanism and provide useful guidance for designing prospective catalysts toward efficient ADN decomposition., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Mercury (Hg) is an important hazardous pollutant that can cause phytotoxicity and harm human health through the food chain. Recently, rice (Oryza sativa L.) has been confirmed as a potential Hg bioaccumulator. Although the genetic and molecular mechanisms involved in heavy metal absorption and translocation in rice have been investigated for several heavy metals, Hg is largely neglected. Here, we analyzed one Hg-resistant line in rice (RHg) derived from a DNA methyltransferase-coding gene, OsMET1-2 heterozygous mutant. Compared with its isogenic wild-type (WT), RHg exhibited a significantly higher survival rate after Hg treatment, ameliorated oxidative damage, and lower Hg uptake and translocation. RNAseq-based comparative transcriptomic analysis identified 34 potential Hg resistance-related genes involved in phytohormone signaling, abiotic stress response, and zinc (Zn) transport. Importantly, the elevated expression of Hg resistance-related genes in RHg was highly correlated with DNA hypomethylation in their putative promoter regions. An ionomic analysis unraveled a negative correlation between Zn and Hg in roots. Moreover, Hg concentration was effectively decreased by exogenous application of Zn in Hg-stressed rice plants. Our findings indicate an epigenetic basis of Hg resistance and reveal an antagonistic relationship between Hg and Zn, providing new hints towards Hg detoxification in plants. ENVIRONMENTAL IMPLICATION: Mercury (Hg) as an important hazardous pollutant adversely impacts the environment and jeopardizes human health, due to its chronicity, transferability, persistence, bioaccumulation and toxicity. In this paper, we identified 34 potential genes that may significantly contribute to Hg resistance in rice. We find the expression of Hg resistance-related genes was highly correlated with DNA hypomethylation in their putative promoter regions. Our results also revealed an antagonistic relationship between Hg and Zinc (Zn), providing new hints towards Hg detoxification in plants. Together, findings of this study extend our current understanding of Hg tolerance in rice and are informative to breed seed non-accumulating rice cultivars., 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 © 2023 Elsevier B.V. All rights reserved.)

Background: The lack of effective biomarkers for the treatment of postoperative recurrence in hepatocellular carcinoma (HCC) persists despite lenvatinib therapy. This study aims to identify beta-actin ( ACTB ) as a predictive biomarker for lenvatinib that can facilitate individualized treatment for HCC., Methods: This retrospective study included a subset of patients with HCC who underwent partial hepatectomy, with some receiving postoperative lenvatinib treatment and others not receiving lenvatinib treatment. A propensity score matching (PSM) analysis of patients who underwent treatment with or without lenvatinib following HCC partial hepatectomy was performed. Immunohistochemistry was employed to determine the levels of ACTB expression in HCC samples obtained from matched patients (n=225) enrolled in this study. The X-Tile was employed to determine the optimal cut-off point of ACTB levels for predicting time to recurrence (TTR). To assess the correlation between ACTB levels and lenvatinib efficacy, a subgroup analysis of TTR was conducted. A Cox regression model with an interaction term was utilized to assess the predictive significance of the model. Subsequently, a nomogram was developed and its discriminative ability and predictive accuracy were assessed using the concordance index (C-index) and calibration curve. For the investigation of the ACTB expression, HCC and para-tumoral normal tissues were employed. The patient-derived xenograft (PDX) model was utilized to validate the correlation between ACTB levels and lenvatinib responsiveness., Results: After PSM, a total of 76 patients who underwent postoperative lenvatinib treatment were included in the analysis, with a median TTR of 24.35 months. Early-stage HCC patients with lower levels of ACTB exhibited a more favorable response to lenvatinib therapy compared to those with higher levels. The reduced expression of ACTB was indicative of the benefits of lenvatinib, as opposed to higher levels {hazard ratio (HR) =0.243 [95% confidence interval (CI): 0.096-0.619], P<0.001, P value for interaction =0.014}. In approximately 81.8% of cases involving HCC patients, there was an observed increase in the expression of ACTB . Multivariate analysis of the lenvatinib cohort revealed Child-Pugh [HR =5.416 (95% CI: 1.390-21.104), P=0.015], Barcelona Clinic Liver Cancer (BCLC) stage [HR =2.508 (95% CI: 1.116-5.639), P=0.026], and ACTB [HR =5.879 (95% CI: 2.424-14.259), P<0.001] score as independent factors for TTR, and all were included in the nomogram. The survival probability based on the calibration curve showed that the prediction of the nomogram was in good agreement with the actual observation. The C-index of the nomogram for predicting survival was 0.76 (95% CI: 0.71-0.84). Moreover, the PDXs derived from tumors exhibiting low levels of ACTB expression demonstrated a heightened sensitivity to lenvatinib treatment., Conclusions: In patients with tumors treated with lenvatinib, low ACTB expression can predict a lower risk of recurrence. The validation of this potential biomarker in independent cohorts is necessary prior to its implementation for precision treatment stratification in patients undergoing partial hepatectomy for early-stage HCC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-942/coif). The authors have no conflicts of interest to declare., (2023 Journal of Gastrointestinal Oncology. All rights reserved.)

Objective: Physical activity (PA) is beneficial in reductions of all-cause mortality and dementia. However, whether Alzheimer's disease (AD) risk is modified by PA remains disputable. This meta-analysis aims to disclose the underlying relationship between PA and incident AD., Methods: Pubmed, Embase, Cochrane Library, and Web of Science were retrieved from inception to June 2023. Random-effects models were employed to derive the effect size, represented by hazard ratio (HR) and 95% confidence interval (CI)., Results: Twenty-nine prospective cohort studies involving 2068,519 participants were included. The pooled estimate showed a favorable effect of PA on AD risk decline (HR 0.72, 95% CI 0.65-0.80). This association remained robust after adjusting for maximum confounders (HR 0.85, 95% CI 0.79-0.91). Subgroup analysis of PA intensity demonstrated an inverse dose-response relationship between PA and AD, effect sizes of which were significant in moderate (HR 0.85, 95% CI 0.80-0.93) and high PA (HR 0.56, 95% CI 0.45-0.68), but not in low PA (HR 0.94, 95% CI 0.77-1.15). Regardless of all participants or the mid-life cohort, the protection of PA against AD appeared to be valid in shorter follow-up (<15 years) rather than longer follow-up (≥15 years). In addition to follow-up, the robustness of the estimates persisted in supplementary meta-analyses, meta-regression analyses, and sensitivity analyses., Conclusion: PA intervention reduces the incidence of AD, but merely in moderate to vigorous PA with follow-up of less than 15 years, thus conditionally recommending the popularization of PA as a modifiable lifestyle factor to prevent AD., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Low- and middle-income countries (LMICs) are particularly vulnerable to the threat of antimicrobial resistance (AMR). Use of antibiotics to treat COVID-19 patients during the pandemic may have contributed to increasing the AMR burden, but systematic evidence is lacking., Methods: We searched Web of Science, EMBASE, PubMed, China National Knowledge Infrastructure (CNKI) and VIP databases from 1 December 2019 to 31 March 2021. Interventional and observation studies across all settings that reported antibiotic use in at least 10 COVID-19 patients were included. We restricted publications to English and Chinese languages. Screening and data extraction were undertaken by at least two independent reviewers. Results were synthesized using random-effects meta-analyses. Subgroup analyses and meta-regression were used to explore heterogeneities. This review was registered with PROSPERO (CRD42021288291)., Results: We included 284 studies involving 210 611 participants in 19 countries. The antibiotic prescribing rates (APRs) in COVID-19 inpatients were 71.7% (95% CI 66.7%-76.5%) in China and 86.5% (77.1%-93.9%) in other LMICs, respectively. APR was lower in mild/moderate cases in China [66.9% (57.9%-75.4%) compared with 91.8% (71.4%-100%) in other LMICs]. High APRs were found among pregnant women and the elderly in China. Disparities in APRs of other patient groups were identified. In studies reporting bacterial infections, the prevalence was 17.3% (10.0%-25.9%) in China and 24.9% (0.1%-68.8%) in other LMICs. Several antibiotics on the WHO 'Watch' and 'Reserve' lists were prescribed frequently in LMICs., Conclusions: Inappropriate antibiotic use and high prevalence of antibiotic prescribing were found in COVID-19 inpatients in many LMICs., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)