Search

Postoperative cognitive dysfunction (POCD) is a prevalent neurological complication that can impair learning and memory for days, months, or even years after anesthesia/surgery. POCD is strongly associated with an altered composition of the gut microbiota (dysbiosis), but the accompanying metabolic changes and their role in gut-brain communication and POCD pathogenesis remain unclear. Here, the present study reports that anesthesia/surgery in aged mice induces elevated intestinal indoleamine 2,3-dioxygenase (IDO) expression and activity, which shifts intestinal tryptophan (TRP) metabolism toward more IDO-catalyzed kynurenine (KYN) and less gut bacteria-catabolized indoleacetic acid (IAA). Both anesthesia/surgery and intraperitoneal KYN administration induce increased KYN levels that correlate with impaired spatial learning and memory, whereas dietary IAA supplementation attenuates the anesthesia/surgery-induced cognitive impairment. Mechanistically, anesthesia/surgery increases interferon-γ (IFN-γ)-producing group 1 innate lymphoid cells (ILC1) in the small intestine lamina propria and elevates intestinal IDO expression and activity, as indicated by the higher ratio of KYN to TRP. The IDO inhibitor 1-MT and antibodies targeting IFN-γ or ILCs mitigate anesthesia/surgery-induced cognitive dysfunction, suggesting that intestinal ILC1 expansion and the ensuing IFN-γ-induced IDO upregulation may be the primary pathway mediating the shift to the KYN pathway in POCD. The ILC1-KYN pathway in the intestine could be a promising therapeutic target for POCD., 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.)

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, often accompanied by impaired vascular endothelial function in the lower limbs. This dysfunction is characterized by a reduced vasodilatory response, leading to decreased blood flow in the lower limbs and ultimately contributing to the development of diabetic peripheral neuropathy. To delve deeper into this pathological process, the study employed bioinformatics to identify and analyze genes highly active in DPN. The investigation revealed that Membrane metallo-endopeptidase (MME) was effectively mitigated by its antagonist. Male Sprague-Dawley (SD) rats served as the model to systematically explore the intrinsic connection among the nociceptible/orphanin FQ-N/OFQ receptor (N/OFQ-NOP) system, femoral artery blood flow in the lower extremities, MME, and DPN. The rats were randomized into two groups: a control group and a DPN group induced by a single intraperitoneal injection of 55 mg/kg streptozotocin (STZ), with 6 rats in each group. The findings indicated that compared to the control group, the DPN group exhibited a significant reduction in femoral artery blood flow. This was accompanied by a notable increase in serum N/OFQ concentration, heightened expression of opioid-related nociceptive protein receptor 1 (OPRL1) and MME in femoral artery tissues of the lower limbs, and an elevated sciatic nerve stimulation threshold. These results suggest that the serum N/OFQ level in DPN rats is increased, which may promote the occurrence of peripheral neuropathy by up regulating MME and reducing peripheral flow distribution., 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.)

Dimethylsulfoniopropionate (DMSP) is an important organosulfur compound, with key roles in global carbon and sulfur cycling, stress tolerance, chemotaxis, and, potentially, climate regulation. The strain Vibrio sp. D3 was isolated from the surface seawater samples in Qingdao coastal area, which could grow on DMSP as sole carbon source. Here, we report the complete genome sequence of strain D3 and analyzed its genomic characteristics related to the sulfur metabolism, especially DMSP. The genome of strain D3 contains two circular chromosomes of total 5,104,020 bp with a mean GC content of 44.87 %. DMSP transporter gene bccT and acryloy-CoA reductase gene acuI, which is essential in DMSP cleavage, are identified in the genome of Vibrio sp. D3. Potential DMSP demethylase gene dmdA (26.07 %, amino acid sequence identity) and DMSP lyase gene dddX (26.32 %, amino acid sequence identity) are predicted in the genome of strain D3, whose functions need further experimental verification. Vibrio sp. D3 also contains L -Met gamma-lyase (MegL) to generate MeSH from L -Met and complete assimilatory sulfate reduction pathway. Together, the genome of strain D3 reveals the possible DMSP catabolic pathways and supports its role in sulfur cycling., 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.)

Annealing is an ideal approach to synchronizing soluble proteins into their minimum-energy states via tandem heating and cooling treatments. Like soluble proteins, many membrane proteins also suffer intrinsic structural flexibility, the major obstacle to high-resolution structural determination. How to apply annealing onto membrane proteins remains unexplored. Here, we utilized the translocase of the outer mitochondrial membrane (TOM) as the model and investigated the ideal annealing conditions for membrane proteins. After structural determination via cryo-electron microscopy, we indicated that fast cooling the heated TOM complex to 0 °C can significantly improve the local resolution compared with the unannealed one. Structural analyses showed that annealing renders the TOM complex into a new conformation with its Tom7 α1 helix from a reclining position on the membrane surface to a lying orientation, accompanied by the loop between β6 and β7 in Tom40, flipping outward from the Tom40 β-barrel, ideal for preprotein translocation. In all, our results demonstrate the role of annealing in synchronizing membrane proteins and unveil unidentified conformations of the TOM complex., 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 © 2025 Elsevier Inc. All rights reserved.)

Fucoidan, the main polysaccharide in various species of brown seaweed, has a high annual production. It is an important source of marine organic carbon and exhibits diverse biological activities and significant application potential. Rhodopirellula sp. P2, a novel marine bacterium of the phylum Planctomycetota, was isolated from intertidal algae samples collected from the Weihai coast, the Yellow Sea, China. The strain P2 is a Gram-negative, aerobic, and pear-shaped bacterium. Here, we report the complete genome sequence of Rhodopirellula sp. P2. The genome of strain P2 consists of a single circular chromosome with 7,291,416 bp and a GC content of 57.38 %, including 5462 protein-coding genes, 2 rRNA genes, and 48 tRNA genes. Genomic analysis revealed that strain P2 possessed 173 CAZymes and 106 sulfatases, indicating that strain P2 has the potential ability to utilize multiple polysaccharides, especially hydrolyze fucoidan to fucose. The genome of strain P2 also encodes a gene cluster related to bacterial microcompartment, suggesting the ability of strain P2 to metabolize fucose. These results enhance the understanding of the diversity and ecological functions of Planctomycetota, and also facilitate the exploitation of Planctomycetota and enzyme resources to utilize fucoidan. This study provides genetic insights into fucoidan catabolism by Planctomycetota, expanding our understanding of fucoidan-degrading microbial groups., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The deep marine sediments represent a major repository of organic matter whilst hosting a great number of uncultivated microbes. Microbial metabolism plays a key role in the recycling of organic matter in the deep marine sediments. D-amino acids (DAAs) and DAA-containing muropeptides, an important group of organic matter in the deep marine sediments, are primarily derived from bacterial peptidoglycan decomposition. Archaea are abundant in the deep ocean microbiome, yet their role in DAA metabolism remains poorly studied. Here, we report bioinformatic investigation and enzymatic characterization of deep marine sedimentary archaea involved in DAA metabolism. Our analyses suggest that a variety of archaea, particularly the Candidatus Bathyarchaeota and the Candidatus Lokiarchaeaota, can metabolize DAAs. DAAs are converted into L-amino acids via amino acid racemases (Ala racemase, Asp racemase and broad substrate specificity amino acid racemase), and converted into α-keto acid via d-serine ammonia-lyase, whereas DAA-containing di-/tri-muropeptides can be hydrolyzed by peptidases (dipeptidase and D-aminopeptidase). Overall, this study reveals the identity and activity of deep marine sedimentary archaea involved in DAA metabolism, shedding light on the mineralization and biogeochemical cycling of DAAs in the deep marine sediments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Cadmium (Cd) is a common environmental metal. Previous studies indicated that long-term respiratory Cd exposure caused lung injury and airway inflammation. The purpose of this study was to evaluate whether short-term respiratory Cd exposure induces pulmonary ferroptosis and NLRP3 inflammasome activation. Adult C57BL/6J mice were exposed to Cd by inhaling CdCl 2 aerosol (0, 10, or 100 ppm) for 5 days. Serum and lung Fe 2+ contents were elevated in Cd-exposed mice. Oxidized AA metabolites, the major oxidized lipids during ferroptosis, were upregulated in Cd-exposed mouse lungs. Pulmonary MDA content and 4-HNE-positive cells were increased in Cd-exposed mice. ACSL4 and COX-2, two lipoxygenases, were upregulated in Cd-exposed mouse lungs. Further analyses found that phosphorylated NF-kB p65 was elevated in Cd-exposed mouse lungs. Innate immune receptor protein NLRP3 and adapter protein ASC were upregulated in Cd-exposed mouse lungs. Caspase-1 was activated and IL-1β and IL-18 were upregulated in Cd-exposed mouse lungs. Fer-1, a specific inhibitor of ferroptosis, attenuated Cd-induced elevation of pulmonary NLRP3 and ASC, caspase-1 activation, and IL-1β and IL-18 upregulation. Finally, mitoquinone (MitoQ), a mitochondria-target antioxidant, suppressed Cd-caused ferroptosis and NLRP3 inflammasome activation. Our results demonstrate that ferroptosis might partially mediate Cd-evoked activation of NLRP3 inflammasome in the lungs., 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.)

In this study, an active film composed of gallic acid (GA), chitosan (CS), and cellulose nanocrystals (CNC) was prepared using a solution casting method and synergistic photodynamic inactivation (PDI) technology. Characterization of the film showed that the CS-CNC-GA composite film had high transparency and UV-blocking ability. The addition of GA (0.2 %-1.0 %) significantly enhanced the mechanical properties, water resistance, and thermal stability of the film. The tensile strength increased up to 46.30 MPa, and the lowest water vapor permeability was 1.16 × e -12 g/(cm·s·Pa). The PDI-treated CS-CNC-GA1.0 composite film exhibited significantly enhanced antibacterial activity, with inhibition zone diameters of 31.83 mm against Staphylococcus aureus and 21.82 mm against Escherichia coli. The CS-CNC-GA composite film also showed good antioxidant activity. Additionally, the CS-CNC-GA 1.0 composite film generated a large amount of singlet oxygen under UV-C light irradiation. It was found that using the CS-CNC-GA 1.0 composite film for packaging and storage of oysters at 4 °C effectively delayed the increase in pH, total colony count, and lipid oxidation in oysters. In conclusion, the CS-CNC-GA composite film based on PDI technology has great potential for applications in the preservation of aquatic products., 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.)

Arsenic is a toxic element widely distributed in the Earth's crust and ranked as a class I human carcinogen. Microbial metabolism makes significant contributions to arsenic detoxification, migration and transformation. Nowadays, research on arsenic is primarily in areas affected by arsenic pollution associated with human health activities. However, the biogeochemical traits of arsenic in the global marine ecosystem remain to be explicated. In this study, we revealed that seawater environments were primarily governed by the process of arsenate reduction to arsenite, while arsenite methylation was predominant in marine sediments which may serve as significant sources of arsenic emission into the atmosphere. Significant disparities existed in the distribution patterns of the arsenic cycle between surface and deep seawaters at middle and low latitudes, whereas these situations tend to be similar in the Arctic and Antarctic oceans. Significant variations were also observed in the taxonomic diversity and core microbial community of arsenic cycling across different marine environments. Specifically, γ-proteobacteria played a pivotal role in the arsenic cycle in the whole marine environment. Temperature, dissolved oxygen and phosphate were the crucial factors that related to these differentiations in seawater environments. Overall, our study contributes to a deeper understanding of the marine arsenic cycle., 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.)

Phthalate esters (PAEs) are emerging hazardous and toxic chemicals that are extensively used as plasticizers or additives. Diethyl phthalate (DEP) and dimethyl phthalate (DMP), two kinds of PAEs, have been listed as the priority pollutants by many countries. PAE hydrolases are the most effective enzymes in PAE degradation, among which family IV esterases are predominate. However, only a few PAE hydrolases have been characterized, and as far as we know, no crystal structure of any PAE hydrolases of the family IV esterases is available to date. HylD1 is a PAE hydrolase of the family IV esterases, which can degrade DMP and DEP. Here, the recombinant HylD1 was characterized. HylD1 maintained a dimer in solution, and functioned under a relatively wide pH range. The crystal structures of HylD1 and its complex with monoethyl phthalate were solved. Residues involved in substrate binding were identified. The catalytic mechanism of HylD1 mediated by the catalytic triad Ser140-Asp231-His261 was further proposed. The hylD1 gene is widely distributed in different environments, suggesting its important role in PAEs degradation. This study provides a better understanding of PAEs hydrolysis, and lays out favorable bases for the rational design of highly-efficient PAEs degradation enzymes for industrial applications in future., 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 gut microbiota and neurological development of neonatal mice are susceptible to environmental factors that may lead to altered behavior into adulthood. However, the role that changed gut microbiota and neurodevelopment early in life play in this needs to be clarified. In this study, by modeling early-life environmental changes by cross-fostering BALB/c mice, we revealed the effects of the environment during the critical period of postnatal development on adult social behavior and their relationship with the gut microbiota and the nervous system. The neural projections exist between the ascending colon and oxytocin neurons in the paraventricular nuclei (PVN), peripheral oxytocin levels and PVN neuron numbers decreased after cross-fostering, and sex-specific alteration in gut microbiota and its metabolites may be involved in social impairments and immune imbalances brought by cross-fostering via the gut-brain axis. Our findings also suggest that social cognitive impairment may result from a combination of PVN oxytocinergic neurons, gut microbiota, and metabolites., 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.)

Background: The low-fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet (LFD) has been associated with reduced symptomology in pediatric functional gastrointestinal disorders (FGIDs). The LFD is a complex dietary intervention that may be difficult to follow; thus, there is great interest in determining factors that contribute to adherence., Objective: To examine whether baseline abdominal pain, emotional/behavioral problems, or quality of life predict adherence to the LFD in children with FGIDs., Design: This was a single-group pre-post intervention design within a larger randomized controlled trial., Participants/setting: Thirty 7- to 12-year-old children with FGIDs were recruited from pediatric gastrointestinal and primary care settings throughout Texas from 2019 to 2021. Evaluated participants were randomized to an LFD intervention as part of a larger randomized controlled trial., Intervention: Participants received dietary counseling and followed the LFD for 3 weeks., Measures: Emotional or behavioral problems and quality of life were obtained via parent report, and abdominal pain was measured via child report. Adherence was assessed by using diet records and computed by a decrease in consumption of overall FODMAP intake., Statistical Analyses Performed: A hierarchical generalized linear mixed regression model examined factors associated with adherence., Results: Greater baseline quality of life was associated with better adherence to the LFD (beta coefficient β = -.02, P = 0.03), and baseline emotional/behavioral problems and abdominal pain complaints were not significantly associated with adherence (all Ps > 0.28)., Conclusions: Higher child quality of life as reported by parents was related to increased adherence to this complex dietary intervention., (Copyright © 2024 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Six previously undescribed diterpenoid glucosides, along with four known compounds, were isolated from the aerial parts of Sigesbeckia glabrescens. The structures and absolute configurations of undescribed compounds were elucidated using extensive spectroscopic techniques, ECD calculations and chemical methods. Compounds 1 and 8 exhibited anti-inflammatory activity against LPS-induced NO production in RAW 264.7 macrophages, with compound 8 demonstrating significant inhibitory activity compared to positive control minocycline, boasting an IC 50 value at 14.20 μM., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

The occurrence of cardiovascular events in diabetic patients during the perioperative period is related to the activation of sympathetic nerves. Basic research shows that serum nociceptin/orphanin FQ (N/OFQ) levels in diabetic neuropathy rats increased, and N/OFQ reduces the release of norepinephrine (NE). We hypothesize that N/OFQ will affect the sympathetic nervous system during perioperative myocardium of diabetic patients. 66 patients with unilateral knee arthroplasty were divided into diabetes group (D group) and non-diabetes group (N group). Measured blood glucose, serum NE, N/OFQ concentrations at the 30 min before anesthesia (T0), 1 h after surgery (T1), 24 h after surgery (T2) and the cardiac troponinI (cTnI) concentration at T0 and T2. Compared with N group, the concentration of blood glucose, N/OFQ and cTnI in D group was higher and the NE was lower at T0 (P < 0.05). At T1, the blood glucose, N/OFQ, NE concentrations of D group increased, only the blood glucose increased in N group (P < 0.05). Serum N/OFQ of D group from T0 to T1 was correlated with the change trend of blood glucose, NE concentration from T0 to T1 and cTnI from T0 to T2(r = 0.386, P = 0.027; r = 0.350, P = 0.046; r = 0.363, P = 0.038). The outcomes demonstrated that the preoperative serum N/OFQ concentration in diabetic patients was increased, and the increase in N/OFQ concentration during the operation was related to the increase in NE and cTnI concentrations, perioperative N/OFQ may mediate myocardial injury through sympathetic nervous system., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Pathological cardiac hypertrophy (CH) is driven by maladaptive changes in myocardial cells in response to pressure overload or other stimuli. CH has been identified as a significant risk factor for the development of various cardiovascular diseases, ultimately resulting in heart failure. Melanoma differentiation-associated protein 5 (MDA5), encoded by interferon-induced with helicase C domain 1 (IFIH1), is a cytoplasmic sensor that primarily functions as a detector of double-stranded ribonucleic acid (dsRNA) viruses in innate immune responses; however, its role in CH pathogenesis remains unclear. Thus, the aim of this study was to examine the relationship between MDA5 and CH using cellular and animal models generated by stimulating neonatal rat cardiomyocytes with phenylephrine and by performing transverse aortic constriction on mice, respectively. MDA5 expression was upregulated in all models. MDA5 deficiency exacerbated myocardial pachynsis, fibrosis, and inflammation in vivo, whereas its overexpression hindered CH development in vitro. In terms of the underlying molecular mechanism, MDA5 inhibited CH development by promoting apoptosis signal-regulating kinase 1 (ASK1) phosphorylation, thereby suppressing c-Jun N-terminal kinase/p38 signaling pathway activation. Rescue experiments using an ASK1 activation inhibitor confirmed that ASK1 phosphorylation was essential for MDA5-mediated cell death. Thus, MDA5 protects against CH and is a potential therapeutic target., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Cigarette smoking is commonly reported among chronic pain patients in the clinic. Although chronic nicotine exposure is directly linked to nociceptive hypersensitivity in rodents, underlying neurobiological mechanisms remain unknown., Methods: Multi-tetrode recordings in freely moving mice were used to test the activity of dopaminergic projections from the ventral tegmental area (VTA) to pyramidal neurones in the anterior cingulate cortex (ACC) in chronic nicotine-treated mice. The VTA→ACC dopaminergic pathway was inhibited by optogenetic manipulation to detect chronic nicotine-induced allodynia (pain attributable to a stimulus that does not normally provoke pain) assessed by von Frey monofilaments (force units in g)., Results: Allodynia developed concurrently with chronic (28-day) nicotine exposure in mice (0.36 g [0.0141] vs 0.05 g [0.0018], P<0.0001). Chronic nicotine activated dopaminergic projections from the VTA to pyramidal neurones in the ACC, and optogenetic inhibition of VTA dopaminergic terminals in the ACC alleviated chronic nicotine-induced allodynia in mice (0.06 g [0.0064] vs 0.28 g [0.0428], P<0.0001). Moreover, optogenetic inhibition of Drd2 dopamine receptor signalling in the ACC attenuated nicotine-induced allodynia (0.07 g [0.0082] vs 0.27 g [0.0211], P<0.0001)., Conclusions: These findings implicate a role of Drd2-mediated dopaminergic VTA→ACC pathway signalling in chronic nicotine-elicited allodynia., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

In this work, we reported a fluorescent probe Fur-SH, a derivative of benzofuranone, which was used to detect H 2 S in living cells and zebrafish. Based on the three structural characteristics of the probe, the effects of different structural modifications on the optical properties of the fluorophore were compared. Then, the fluorophore Fur-OH was synthesized by modifying diethylamino group with benzofuranone as the main skeleton. With 2,4-dinitrofluorobenzene as the recognition group and diethylamino as the electron donor, the push-pull electron effect occurred with nitro group, which led to fluorescence quenching, and an openable fluorescent probe Fur-SH was formed. The probe Fur-SH (λ ex  = 510 nm; λ em  = 570 nm) had the advantages of smaller full width at half maxima, rapid response (5 min) and wide pH window. The quantitative properties of the probe were excellent, reaching saturation at 50 equivalents of substrate. The probe Fur-SH showed high sensitivity to H 2 S, with LOD of 48.9 nM and LOQ of 50 nM. At present, the probe Fur-SH had been applied to fluorescence imaging of MCF-7 cells and zebrafish. By comparing the effects of different structures on the optical properties of fluorophores, this work was expected to be helpful to the development of fluorescent probes in the future., 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.)

It has recently been found that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) m6A modifications can affect viral replication and function. However, no studies to date have shown a correlation between SARS-CoV-2 m6A modifications and viral pathogenicity. In this study, we analyzed m6A modification in 2,190,667 SARS-CoV-2 genomic RNAs. m6A modifications of SARS-CoV-2 from different lineages, causing mild or severe COVID-19 and showing breakthrough for different vaccines were analyzed to explore correlations with viral pathogenicity. The results suggested that the presence of more m6A modifications in the SARS-CoV-2 N region (positive strand) correlates with weaker pathogenicity. In addition, we identified three m6A modification sites correlating with weak pathogenicity (924 in ORF1ab, 15,659 in ORF1ab, 28,288 in N, 28,633 in N and 29,385 in N, 29,707 in 3'UTR) and one with strong pathogenicity (74 in 5'UTR). These results provide new information for understanding the prevalence of SARS-CoV-2 and controlling the virus., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

A polysaccharide CY-2 from C. yunnanensis was obtained through a process of consecutive water extraction, alcohol precipitation, and DEAE-52 fast-flow chromatography. CY-2, with an average molecular weight of 2.69 × 10 4  Da mainly consisted of glucose and mannose with a molar ratio of 33.5: 56.9. Infrared spectrum (IR), methylation analysis, and nuclear magnetic resonance (NMR) results revealed that CY-2 may have a backbone consisting of →6)-α-D-Manp-(1 → 3)-β-D-Glcp-(1→, and branch chain β-D-Glcp-(1→. Meanwhile, CY-2 had a higher inhibition rate on α-glucosidase activity compared with other fractions (CY-0, CY-1, and CY-4) and was a mixed competitive inhibitor. In addition, CY-2 at the concentration of 10 μg/mL presented a superior power to improve glucose consumption and metabolism in HepG2 cells compared with metformin. Overall, these findings highlight the potential value of CY-2 as a hypoglycemic agent., Competing Interests: Declaration of competing interest The authors confirm that there are no known conflicts of interest associated with this publication., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Genetic Creutzfeldt-Jakob disease with T188K mutation (T188K gCJD) is the most frequent genetic prion disease in China. To explore the penetration of T188K mutation and the pathogenesis of T188K gCJD, we constructed 2 lines of transgenic mouse models: homozygous Tg188K +/+ mice containing T188K mutation in 2 alleles of human PRNP background and heterozygous Tg188K +/- mice containing 1 allele of T188K human PRNP and 1 allele of the wild-type mouse PRNP. Spontaneous neurological illnesses were identified in all Tg188K mice at their old ages (750-800 days old). About half of the Tg188K mice died prior to the final observation (930 days old). Extensive spongiosis, PrP Sc deposit, and reactive gliosis of astrocytes and microglia are neuropathologically identified, showing time-dependent exacerbation. Proteinase K-resistant PrP was detected in the brain, muscle, and intestine tissues, and positive real-time quaking-induced conversion reactions were elicited by the brain and muscle tissues of Tg188K mice. Those data verify that the constructed Tg188K mice highly mimic the clinicopathology of human T188K gCJD, strongly indicating the pathogenicity of T188K mutated PrP., Competing Interests: Declaration of Competing Interest Neither the entire study nor any part of it has been published, accepted for publication, or under consideration for publication elsewhere. All authors declare no conflict of interest. All authors have read the paper and approved its submission., (Copyright © 2023. Published by Elsevier Inc.)

The canine mammary tumor is the most common tumor type in female dogs and seriously threatens their life. Currently, no effective treatments are available for this condition. Hence, it is essential to identify biomarkers that positively influence the early diagnosis and treatment and prognosis of this disease. To provide a basis for early diagnosis of canine breast tumors, in this study, 23 dogs with mammary tumors were identified via histopathological examination combined with ancillary diagnoses via blood examinations and diagnostic imaging. The canine mammary tumor and tumor-adjacent healthy tissues were collected, and their metabolites were identified utilizing a UHPLC-qTOF-MS-based untargeted metabolomics approach. The metabolic results revealed a total of 979 ion features in the positive polarity mode and 371 ion features in the negative polarity mode in the tissues of two groups; among them, 536 differential metabolites (385 in the positive and 151 in the negative polarity mode) were analyzed by PCA and PLS-DA. Subsequently, the enrichment pathways purine metabolism, alpha-linolenic acid metabolism, vitamin B6 metabolism, and fatty acid biosynthesis were analyzed using Metaboanalyst 4.0, which suggested that these pathways were valuable diagnostic and therapeutic targets. Moreover, the receiver operating characteristic curves further confirmed 13Z,16Z-docosadienoic acid, 23-nordeoxycholic acid, and (±)12(13)-DiHOME as expected candidate biomarkers of canine mammary tumors. In conclusion, the discovery of tumor biomarkers based on untargeted metabolomics is informative for pathological mechanism studies and facilitates the early diagnosis of canine mammary tumors., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The anterior clinoid process (ACP) is surrounded by nerves and vessels that, together, constitute an intricate anatomical structure with variations that challenges the performance of individualized anterior clinoidectomy in treating lesions with different extents of invasion. In the present study, we established a 6-surface system for the ACP based on anatomical landmarks and analyzed its value in guiding ACP drilling and resection of paraclinoid meningiomas., Methods: Using the anatomical characteristics of 10 dry skull specimens, we set 9 anatomical landmarks to delineate the ACP into 6 surfaces. Guided by our 6-surface system and eggshell technique, 5 colored silicone-injected anatomical specimens were dissected via a frontotemporal craniotomy to perform anterior clinoidectomy. Next, 3 typical cases of paraclinoid meningioma were selected to determine the value of using our 6-surface system in tumor resection., Results: Nine points (A-H and T) were proposed to delineate the ACP surface into frontal, temporal, optic nerve, internal carotid artery, cranial nerve III, and optic strut surfaces according to the adjacent tissues. Either intradurally or extradurally, the frontal and temporal surfaces could be identified and drilled into depth, followed by skeletonization of the optic nerve, cranial nerve III, internal carotid artery, and optic strut surfaces. After the residual bone was removed, the ACP was drilled off. In surgery of paraclinoid meningiomas, our 6-surface system provided great benefit in locating the dura, nerves, and vessels, thus, increasing the safety of opening the optic canal and relaxing the oculomotor or optic nerves and allowing for individualized ACP drilling for meningioma removal., Conclusions: Our 6-surface system adds much anatomical information to the classic Dolenc triangle and can help neurosurgeons, especially junior ones, to increase their understanding of the paraclinoid spatial structure and accomplish individualized surgical procedures with high safety and minimal invasiveness., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Misdiagnosis of central facial palsy (CFP) as peripheral facial palsy (PFP) can lead to serious consequences clinically. It is unknown whether the leukocyte counts (leukocyte), neutrophil counts (neutrophil), and neutrophil to lymphocyte ratio (NLR) can be used to distinguish CFP from PFP., Methods: Of the total 152 patients admitted for acute facial paralysis, 76 CFP patients (CFP group) caused by acute ischemic stroke (AIS) and 76 PFP cases (PFP group) without AIS were enrolled in this retrospective study. The levels of blood leukocyte, neutrophil, lymphocyte, platelet counts (platelet), NLR, and platelet to lymphocyte ratio (PLR) before or upon admission were recorded and compared between the two groups. The student t-test was adopted for comparison of the mean. Model discrimination was evaluated using the area under the receiver operating characteristic curve (AUC). Comparison of AUC was performed using the Z-test., Results: Compared with PFP group, the levels of leukocyte, neutrophil, and NLR were significantly increased in CFP group (all p < 0.01), and there were still significantly statistical differences (all p < 0.01), even after adjusting for age, gender, and past medical history, while no significantly statistical differences of lymphocyte, platelet, and PLR were found between CFP and PFP (all p > 0.05); furthermore, the AUC in distinguishing CFP from PFP were 0.629, 0.671, and 0.657 for leukocyte, neutrophil, and NLR, respectively, and no significant difference of AUC was observed among leukocyte, neutrophil, and NLR (p > 0.05); finally, the cutoff values (specificity, sensitivity, and Youden index) in distinguishing CFP from PFP were 7.08 × 10 9 /L (65.79%, 57.89%, 0.237) for leukocyte, 4.90 × 10 9 /L (73.68%, 60.53%, 0.342) for neutrophil, and 2.88 (72.37%, 55.26%, 0.276) for NLR, respectively., Conclusions: As easy-to-obtain and inexpensive inflammatory biomarkers, leukocyte, neutrophil, and NLR could demonstrate diagnostic values in distinguishing between CFP and PFP., Competing Interests: Declaration of Competing Interest The authors report no competing financial interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Talaromyces marneffei is an emerging pathogen, and the number of infections in HIV-negative individuals is rapidly increasing. Nevertheless, there is no sufficient comprehensive report on this issue, and awareness needs to be raised among clinicians., Methods: We analyzed the differences in the clinical data of patients who are HIV-negative and HIV-positive with Talaromyces marneffei infection (TMI) from 2018 to 2022., Results: A total of 848 patients were included, among whom 104 were HIV-negative. The obvious differences between the HIV-positive and HIV-negative groups were as follows: (i) the patients who are HIV-negative were older and more likely to exhibit cough and rash, (ii) the time in days from symptom onset to diagnosis among patients who are HIV-negative was longer, (iii) the laboratory findings and radiological presentations seemed more severe in patients who are HIV-negative, (iv) differences were observed regarding the underlying conditions and co-infection pathogens, and correlation analysis showed that correlations existed for many indicators, (v) and persistent infection was more likely to occur in patients who are HIV-negative., Conclusion: TMI in patients who are HIV-negative differs from that in patients who are HIV-positive in many aspects, and more investigations are needed. Clinicians should be more aware of TMI in patients who are HIV-negative., Competing Interests: Declaration of competing interests The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Nearly half of all Asian non-small cell lung cancer (NSCLC) patients harbour epidermal growth factor receptor (EGFR) mutations, and first-generation EGFR tyrosine kinase inhibitors (TKIs) are one of the first-line treatments that have improved the outcomes of these patients. Unfortunately, 20% of these patients can not benefit from the treatment. The basis of this primary resistance is poorly understood. Therefore, overcoming EGFR-TKI primary resistance and maintaining the efficacy of TKIs has become a key issue. β-Elemene, a sesquiterpene compound extracted from Curcuma aromatica Salisb. (wenyujing), has shown potent antitumor effects. In this research, we found that β-elemene combined with erlotinib enhanced the cytotoxicity of erlotinib to primary EGFR-TKI-resistant NSCLC cells with EGFR mutations and that ferroptosis was involved in the antitumor effect of the combination treatment. We found that lncRNA H19 was significantly downregulated in primary EGFR-TKI-resistant NSCLC cell lines and was upregulated by the combination treatment. Overexpression or knockdown of H19 conferred sensitivity or resistance to erlotinib, respectively, in both in vitro and in vivo studies. The high level of H19 enhanced the cytotoxicity of erlotinib by inducing ferroptosis. In conclusion, our data showed that β-elemene combined with erlotinib could enhance sensitivity to EGFR-TKIs through induction of ferroptosis via H19 in primary EGFR-TKI-resistant lung cancer, providing a promising strategy to overcome EGFR-TKI resistance in NSCLC patients., Competing Interests: Declarations of 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Changes in lake area (water surface area) are often considered accurate and sensitive representations of climate change. However, the role that elevation plays in this dynamic is somewhat unclear; studies remain inconclusive as to whether lake responses are consistent across elevation gradients. Here, we used Landsat and keyhole satellite images to quantify lake area changes from the 1960s to 2020 at different elevations in Central Asia's Tianshan Mountains and relate them to both climatic and anthropogenic factors. The results revealed that all low-elevation lakes showed a decreasing trend, and the total area of all monitored low-elevation lakes was reduced by 18.50 %. The total area of the mid-elevation lakes decreased by 0.16 %, while the total area of the high-elevation glacial lakes increased by 4.35 %. Lakes are recharged by a variety of influxes including glacial meltwater and precipitation. Notably, human activities (urban and agricultural water consumption) were the dominant factors in the shrinkage of low-elevation lakes. Climatic factors were the main driving factors of mid-elevation lake changes, and these lakes appeared to be more sensitive to temperature changes than lakes at other elevations. In addition, significant warming dominated area changes in high-elevation proglacial and unconnected glacial lakes. Overall, those results emphasized that when using lakes to reconstruct paleoclimates or predict lake evolution, it is necessary to consider how elevation gradients and recharge types may affect lake sensitivity to variations in climatic and anthropogenic activity., 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.)

With the soaring number of multidrug-resistant bacteria, it is imperative to develop novel efficient antibacterial agents and discovery new antibacterial pathways. Herein, we designed and synthesized a series of structurally novel glycyrrhetinic acid (GA) derivatives against multidrug-resistant Staphylococcus aureus (MRSA). The in vitro antibacterial activity of these compounds was evaluated using the microbroth dilution method, agar plate coating experiments and real-time growth curves, respectively. Most of the target derivatives showed moderate antibacterial activity against Staphylococcus aureus (S. aureus) and MRSA (MIC = 3.125-25 μM), but inactivity against Escherichia coli (E. Coli) and Pseudomonas aeruginosa (P. aeruginosa) (MIC > 200 μM). Among them, compound 11 had the strongest antibacterial activity against MRSA, with an MIC value of 3.125 μM, which was 32 times and 64 times than the first-line antibiotics penicillin and norfloxacin, respectively. Additionally, transcriptomic (RNA-seq) and quantitative polymerase chain reaction (qPCR) analysis revealed that the antibacterial mechanism of compound 11 was through blocking the arginine biosynthesis and metabolic and the H 2 S biogenesis. Importantly, compound 11 was confirmed to have good biocompatibility through the in vitro hemolysis tests, cytotoxicity assays and the in vivo quail chicken chorioallantoic membrane (qCAM) experiments. Current study provided new potential antibacterial candidates from glycyrrhetinic acid derivatives for clinical treatment of MRSA infections., 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 © 2022 Elsevier Inc. All rights reserved.)

Pyometra is a common and high-incidence reproductive system disease in female dogs, and its development involves both hormonal and bacterial factors. Characterization of the endometrial microbiome in healthy dogs and diseased dogs with pyometra remains unclear at present, however. In this study, dogs with pyometra were identified based on the clinical examinations, hematology examinations, vaginal smears and uterine histopathology. The endometrial samples of healthy dogs (n = 30) and diseased dogs (n = 41) were then collected and sequenced by 16S rRNA high-throughput sequencing technology. Dogs with pyometra suffered from inflammation, and their endometrial microbial diversity (ACE and Chao 1 indices) was significantly lower than that of healthy dogs (P < 0.05). The endometrial samples of both groups were enriched in four phyla (Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria), with a greater abundance of Firmicutes in diseased dogs (P < 0.05). At the genus level, the most prevalent microbes in diseased dogs belonged to Pseudomonas, Escherichia-Shigella, Mycoplasma, Enterococcus, Haemophilus, Vibrio and Ralstonia, with lower levels of Mycoplasma, Enterococcus and Haemophilus in the healthy control. Principal co-ordinates analysis and non-metric multi-dimensional scaling showed that the endometrial microbiome of diseased dogs clustered separately from that of the healthy controls (P < 0.05). In the LDA effect size analysis, 18 members of the endometrial microbiome were screened. Of these, the bacterial species Pseudomonas&#95;aeruginosa and microbes within the genera Mycoplasma, Enterococcus and Haemophilus were found to be enriched in the uteruses of diseased dogs. Furthermore, the Random Forests model further confirmed that Mycoplasma and Haemophilus could be considered as biomarkers of diseased endometrium. In conclusion, this study provided a theoretical basis for the development of probiotic preparation in the future., (Copyright © 2022 Elsevier Inc. All rights reserved.)

According to many in the field，the prevalence of Alzheimer's disease (AD) in type II diabetes (T2DM) populations is considerably higher than that in the normal population. Human islet amyloid polypeptide (hIAPP) is considered to be a common risk factor for T2DM and AD. Preliminary observations around T2DM animal model show that the decrease of adult neural stem cells (NSCs) in the subventricular zone (SVZ) is accompanied by olfactory dysfunction. Furthermore, impaired olfactory function could serve as to an early predictor of neurodegeneration，which is associated with cognitive impairment. However, the synergistic effects between hIAPP and amyloid-beta (Aβ) 1 - 42 in the brain and the neurodegeneration remains to be further clarified. In this study, olfactory capacity, synaptic density, status of NSC in SVZ, and status of newborn neurons in olfactory bulb (OB) were assessed 6 months after stereotactic injection of oligomer Aβ 1 - 42 into the dens gyrus (DG) of hIAPP-/+ mice or wild-type homogenous mice. Our results set out that Aβ 42 and amylin co-localized into OB and raised Aβ 42 deposition in hIAPP -/+ mice compared with wild-type brood mice. In addition, 6 months after injection of Aβ 1 - 42 in hIAPP -/+ mice, these mice showed increased olfactory dysfunction, significant loss of synapses, depletion of NSC in SVZ, and impaired cell renewal in OB. Our present study suggested that the synergistic effects between hIAPP and Aβ 1 - 42 impairs olfactory function and was associated with decreased neurogenesis in adults with SVZ., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Postoperative groin complication is a common cause of morbidity in vascular surgery. Prophylactic wound adjuncts addressing this issue have been shown to reduce complications in high-risk patients, but their widespread implementation is limited by their high cost. This study introduces a risk prediction model for patients at a high risk for groin complication which can be accessed through the iPhone application, Vasculink., Methods: A literature search identified risk prediction models for groin complication in vascular surgery. Odds ratios of risk factors that were present in at least 2 published models were calculated with a pooled effect size. The weighted risk for each factor was used to create our model and a cutoff point defining high risk patients was chosen. The initial model was assessed and validated using a split-sample methodology on a cohort identified via a retrospective chart review of all patients undergoing open vascular surgery at our institution between 2017 and 2020. Model performance was assessed using the C-statistic., Results: Risk factors included in our model were female gender, body mass index ≥28 kg/m 2 , ever-smoker, reoperation, use of prosthetic, emergency, and end-stage renal disease. Of 216 patients, 131 were at a high risk. The overall groin complication rate was 43%, and specific complication rates were 27% infection, 14.8% seroma, and 6.9% hematoma. Our model's sensitivity and specificity were 92.47% and 60.98%, respectively. The C-statistic is 0.768., Conclusions: By using risk factors identified in the literature we have been able to establish a highly sensitive risk prediction model for groin complication following open vascular surgery. By incorporating our model into an iPhone application, Vasculink, we hope to facilitate preoperative decision making regarding the use of prophylactic wound adjuncts., (Copyright © 2022 Elsevier Inc. All rights reserved.)

There are an increasing number of clinical studies evaluating different adeno-associated virus (AAV) serotypes as vectors for gene therapy. Long-term frozen storage can maximize the stability of AAV. Freeze-thaw (F/T) cycles and exposures to room temperature (RT) and refrigerated conditions occur during manufacturing, labeling, and clinical use. In this work we exposed AAV8 and AAV9 at low and high concentrations to five F/T cycles compounded with RT and refrigerated holds in a 'daisy chain' time out of intended storage (TOIS) stability study, which may be a best practice in early development. We also evaluated the impact of 5 F/T cycles for multiple permutations of fast and slow cooling and rewarming rates. The quality attributes of AAV8 and AAV9 remained within acceptable ranges after the daisy chain TOIS and F/T rate studies. Potency and concentration were unchanged within method variability. There was a minor increase in non-encapsidated ('free') DNA released from AAV8 after F/T in a phosphate-buffered saline formulation. DNA release during F/T was minimized in a formulation with a low buffer concentration and was not detected in a formulation containing sucrose. We conclude that AAV8 and AAV9 have stability profiles that are suitable for manufacturing and clinical development., Competing Interests: Declaration of Competing Interest All authors are employees of REGENXBIO Inc., which is a clinical-stage AAV gene therapy company. The authors declare no other conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Despite recent advances in diagnosis and therapeutic strategies, treatment of non-small-cell lung cancer (NSCLC) remains unsatisfactory in terms of prognosis. Andrographolide (AD), a principal active component of Andrographis paniculata (Burm.f.) Nees, exerts anti-cancer therapeutic properties. AD has been used for centuries in China for clinical treatment of viral infections. However, the pharmacological biology of AD in NSCLC remains unknown. In this study, AD regulated autophagy and PD-L1 expression in NSCLC. Molecular dynamics simulations indicated that AD bound directly to signal transducer and activator of transcription-3 (STAT3) with high affinity. Proteomics analysis indicated that AD reduced the expression of tumour PD-L1 in NSCLC by suppressing JAK2/STAT3 signalling. AD modulated the P62-dependent selective autophagic degradation of PD-L1 by inhibiting STAT3 phosphorylation. In vivo study revealed that AD suppressed tumour growth in H1975 xenograft mice and Lewis lung carcinoma cell models, and better efficacy was obtained at higher concentrations. AD prolonged the survival time of the mice and enhanced the treatment efficacy of anti-PD-1 mAb immunotherapy by stimulating CD8 + T cell infiltration and function. This work elucidated the specific mechanism by which AD inhibited NSCLC. Treatment with the combination of AD and anti-PD-1 mAb immunotherapy could be a potential strategy for patients with NSCLC., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Pathogen and biofilm contamination in aqueous systems leave millions of people at risk of waterborne diseases. Herein, to address this issue, a green and highly efficient strategy is developed to concurrently trap and kill bacteria, eliminate the debris and the existing biofilm matrix in water environment via magnetic microparticles. The particles (TPFPs) were prepared from the in-situ deposition of Fe 3 O 4 nanoparticles onto the surface of antibacterial functionalized microcrystalline cellulose (MCC). Noticeably, TPFPs can completely inactivate both S. aureus and E. coli once contacting for 30 min by disrupting the bacterial membrane. Meanwhile, the MCC-based magnetic particles retained 100% biocidal efficiency against E. coli (5 * 10 4 E. coli/mg particles) during ten recycling procedures without any treatment. More importantly, according to the results of trapping behavior and antibiofilm assays, not only bacteria could be captured by the particles (trapping rate was over 85%), but also the residual debris from dead bacteria and fragmented biofilm was together removed based on the special structure and functions of the antibacterial particles (~ 80%), including extremely rough surfaces, surficial positive charge and magneto-responsive property. This study presents an efficient approach for microorganism management in water system which can be expectantly applied to improve the water safety., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Halomonas sp. MT13, a moderately psychrotolerant, piezotolerant and exopolysaccharide-producing bacterium, was isolated from deep-sea sediment of the Mariana Trench at the depth of 8300 m. Here, we report the complete genome sequence of strain MT13 and its genomic characteristics related to deep-sea environmental adaptation by comparing with its three closely related Halomonas species. The genome of strain MT13 contains one circular chromosome of 3,643,760 bp without any plasmid. Gene annotation, Cluster of Orthologous Groups (COG) and KEGG analysis showed that strain MT13 possesses a serial of genes involved in deep-sea environmental adaptation, including ectoine biosynthesis, osmolyte transport, and cold-shock response. Compared with type strains of three closely related Halomonas species, strain MT13 has higher proportions of genes assigned to translation, ribosomal structure and biogenesis, and coenzyme, lipid and inorganic ion transport and metabolism, but lacks genes involved in flagellar assembly. The genome of strain MT13 would deepen our knowledge on the adaptation strategies of microorganisms dwelling in deep-sea environment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Postoperative fatigue (POF) is the most common and long-lasting complication after surgery, which brings heavy burden to individuals and society. Recently, hastening postoperative recovery receives increasing attention, but unfortunately, the mechanisms underlying POF remain unclear. Propofol is a wildly used general anesthetic in clinic, and inspired by the rapid antidepressant effects induced by ketamine at non-anesthetic dose, the present study was undertaken to investigate the anti-fatigue effects and underlying mechanisms of propofol at a non-anesthetic dose in 70% hepatectomy induced POF model in rats. We first showed here that single administration of propofol at 0.1 mg/kg ameliorated acute POF in hepatectomy induced POF rats. Based on metabonomics analysis, we hypothesized that propofol exerted anti-fatigue activity in POF rats by facilitating free fatty acid (FFA) oxidation and gluconeogenesis. We further confirmed that propofol restored the deficit in FFA oxidation and gluconeogenesis in POF rats, as evidenced by the elevated FFA utilization, acetyl coenzyme A content, pyruvic acid content, phosphoenolpyruvic acid content, hepatic glucose output and glycogen storage. Moreover, propofol stimulated glucagon secretion and up-regulated expression of cAMP-response element binding protein (CREB), phosphorylated CREB, peroxlsome prolifeator-activated receptor-γ coactivator-1α (PGC-1α), phosphoenolpyruvate carboxykinade1 and carnitine palmitoltransferase 1A. In summary, our study suggests for the first time that propofol ameliorates acute POF by promoting glucagon-regulated gluconeogenesis via CREB/PGC-1α signaling and accelerating FFA beta-oxidation., Competing Interests: Declaration of competing interest The author have declared that no competing interest exists., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Pelagovum pacificum SM1903 T , belonging to a novel genus of the family Rhodobacteraceae, was isolated from the surface seawater of the Mariana Trench. Here, we report the first complete genome sequence of the novel genus Pelagovum. The genome of strain SM1903 T consists of a circular chromosome of 4,040,866 bp and two plasmids of 41,363 bp and 9705 bp, respectively. Gene annotation and metabolic pathway analyses showed that strain SM1903 T possesses a series of genes related to adaptation to marine oligotrophic environments, which are involved in utilization of aromatic compounds, allantoin, and alkylphosphonate, and second messenger signaling in response to the oligotrophic stress. This strain also contains a variety of genes involved in coping with other stresses including osmotic stress, oxidative stress, cold shock, and heat shock. These features would assist this strain to survive under the natural nutrient limitation and other stresses from the environment. The genome of strain SM1903 T of the novel genus Pelagovum would deepen our knowledge on marine bacterioplankton and their adaption strategies to marine oligotrophic environments., (Copyright © 2021. Published by Elsevier B.V.)

Atherosclerosis, as a chronic inflammatory disease within the arterial wall, is a leading cause of morbidity and mortality worldwide due to its role in myocardial infarction, stroke and peripheral artery disease. Additional evidence is emerging that the angiopoietin-like (ANGPTL) family of proteins participate in the pathology of this disease process via endothelial dysfunction, inflammation, dyslipidemia, calcification, foam cell formation and platelet activation. This review summarizes current knowledge on the ANGPTL family of proteins in atherosclerosis related pathological processes. Moreover, the potential value of ANGPTL family proteins as predictive biomarkers in atherosclerosis is discussed. Given the attractive role of ANGPTL3, ANGPTL4, ANGPTL8 in atherosclerotic dyslipidemia via regulation of lipoprotein lipase (LPL), antisense oligonucleotide or/and monoclonal antibody-based inactivation of these proteins represent potential atherosclerotic therapies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Cysteiniphilum litorale is a Gram-negative coccobacillus first isolated from the seawater of Wailingding Island near the estuary of Pearl River in southern China. This organism was previously not considered to cause disease in animals or humans. We report a case of a 19-year-old female patient infected with abscess caused by C. litorale in the middle digit of her right hand after minor trauma during the handling of estuarine shrimps at home. C. litorale was cultured from the wound exudate of the patient and identified by 16S rRNA gene sequencing. Whether C. litorale may be transmitted to humans via other channels requires further exploration., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2021 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Atherosclerosis (AS), a chronic arterial disease, is characterized by endothelial dysfunction, inflammatory reactions and lipid accumulation in parallel with aberrant angiogenesis and vascular smooth muscle cell (VSMC) proliferation. Adipose tissue has been suggested to have an integral influence on metabolism and endocrine secretion, while there have been increasing concerns about the possible involvement of adipokines in cardiovascular diseases, including AS. Here, we focused on chemerin, an adipokine highly expressed in adipose tissue, with strong evidence of an association with inflammation, endothelial dysfunction, metabolic disorder, aberrant angiogenesis, VSMC proliferation and calcification. In this review, we discuss chemerin and its receptors in the pathogenesis of AS. However, the existing data assign various, even contradictory, roles to chemerin in atherosclerosis, such as inhibiting vascular calcification and impairing endothelial function. Current studies focusing on its anti- and pro-atherogenic effects have pinpointed its distinct role in specific cell types and contexts in the pathogenesis of atherosclerosis. Therefore, the gaps in current knowledge regarding the specific role played by chemerin in the etiology of AS require additional future studies. It seems reasonable to suggest that targeted chemerin therapy can be developed as an innovative approach for treating AS., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Adeno-associated virus (AAV) vectors for gene therapy have potential to provide a durable treatment response for a number of diseases with unmet need. DNA is released from AAV capsids at high temperatures. Less is known about DNA release that may occur under conditions relevant to clinical and commercial manufacturing, storage, and distribution. In this work we developed and applied a sensitive fluorescent dye-based method to quantitate trace levels of DNA released from AAV capsids. The method was used to characterize the impact of manufacturing process steps on the increase (up to 1.5%) and removal (down to 0.2%) of free DNA. Free DNA increased by 0.3% per day at 37 °C and by 0.4% per freeze/thaw cycle in a phosphate-buffered saline formulation. When stored for 2 years at different temperatures, free DNA remained low (<0.6%) at both ≤ -60 °C and at 2-8 °C but was higher (2.6%) when the same sample was stored at -20 °C. The dye-based method may be used to further characterize release of free DNA for different processes, formulations, and stress conditions. Overall, release of free DNA was a relatively minor degradation pathway under the conditions studied in this work., Competing Interests: Declaration of Competing Interest All authors are, or were, employees of REGENXBIO Inc. which is a clinical-stage AAV gene therapy company. The authors declare no other conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Currently, conventional methods of treating non-small cell lung cancer (NSCLC) have many disadvantages. An alternative effective therapy with minimal adverse reactions is urgently needed. Weijing decoction (WJD), which is a classic ancient Chinese herbal prescription, has been used successfully to treat pulmonary system diseases containing lung cancer in the clinic. However, the key active component and target of Weijing decoction are still unexplored. Therefore, for the first time, our study aims to investigate the pharmacological treatment mechanism of Weijing decoction in treating NSCLC via an integrated model of network pharmacology, metabolomics and biological methods. Network pharmacology results conjectured that Tricin is a main bioactive component in this formula which targets PRKCA to suppress cancer cell growth. Metabolomics analysis demonstrated that sphingosine-1-phosphate, which is regulated by sphingosine kinase 1 and sphingosine kinase 2, is a differential metabolite in plasma between the WJD-treated group and the control group, participating in the sphingolipid signaling. In vitro experiments demonstrated that Tricin had vital effects on the proliferation, pro-apoptosis, migration and colony formation of Lewis lung carcinoma cells. Through a series of validation assays, Tricin inhibited the tumor growth mainly by suppressing PRKCA/SPHK/S1P signaling and antiapoptotic signaling. On the other hand, Weijing formula could inhibit the tumor growth and prolong the survival time. A high dosage of Tricin was much more potent in animal experiments. In conclusion, we confirmed that Weijing formula and its primary active compound Tricin are promising alternative treatments for NSCLC patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Vascular calcification (VC), which is closely associated with significant mortality in cardiovascular disease, chronic kidney disease (CKD), and/or diabetes mellitus, is characterized by abnormal deposits of hydroxyapatite minerals in the arterial wall. The impact of oxidative stress (OS) on the onset and progression of VC has not been well described. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, xanthine oxidases, myeloperoxidase (MPO), nitric oxide synthases (NOSs), superoxide dismutase (SOD) and paraoxonases (PONs) are relevant factors that influence the production of reactive oxygen species (ROS). Furthermore, excess ROS-induced OS has emerged as a critical mediator promoting VC through several mechanisms, including phosphate balance, differentiation of vascular smooth muscle cells (VSMCs), inflammation, DNA damage, and extracellular matrix remodeling. Because OS is a significant regulator of VC, antioxidants may be considered as novel treatment options., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Non-small cell lung cancer (NSCLC) is one of the most frequently diagnosed cancers and the leading causes of cancer death worldwide. Therefore, new therapeutic agents are urgently needed to improve patient outcomes. Plumbagin (PLB), a natural sesquiterpene present in many Chinese herbal medicines, has been reported for its anti-cancer activity in various cancer cells. In this study, the effects and underlying mechanisms of PLB on the tumorigenesis of NSCLC were investigated. PLB dose-dependently inhibited the growth of NSCLC cell lines. PLB promoted ROS production, activated the endoplasmic reticulum (ER) stress pathway, and induced cell apoptosis, accompanied by the decreased expression level of ADP-ribosylation factor 1 (ARF1) in NSCLC cancer cells, and those effects of PLB could be reversed by the pretreatment with N-acetyl-L-cysteine (NAC). More importantly, the calcium chelator (BM) significantly reversed PLB-induced cell apoptosis. Furthermore, PLB significantly inhibited the growth of both H1975 xenograft and LLC1 tumors and exhibited antitumor activity by enhancing the number and the effector function of CD8 + T cells in KRASLA2 mice model and the LLC1 xenograft. Our findings suggest that PLB exerts potent antitumor activity against NSCLC in vitro and in vivo through ARF1 downregulation and induction of antitumor immune response, indicating that PLB is a new novel therapeutic candidate for the treatment of patients with NSCLC., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Alkaline phosphatase (ALP), as an immunological label, is widely used in biochemical assays. Here, a simple yet effective strategy for ALP activity detection was proposed on the basis of in situ formation of Prussian blue nanoparticles and polychromatic superposition effect. Firstly, ascorbic acid, a product from ALP-catalyzed hydrolysis of 2-phospho-l-ascorbic acid (AAP), converted yellow ferricyanide into ferrocyanide. Then, the specific reaction between ferrocyanide and ferric ions (Fe 3+ ) initiated the generation of Prussian blue nanoparticles in situ. Meanwhile, the residual AAP chelated with Fe 3+ , and a stable Fe 3+ -AAP complex was quickly formed. When Prussian blue nanoparticles mixed with brown Fe 3+ -AAP complex and yellow ferricyanide at different ratios, a distinct color variation was presented. Therefore, a sensitive multicolor assay of ALP activity with a detection limit of 1.0 U/L was realized by simply blending commercially available reagents. Furthermore, magnetic sandwich and competitive sensing platforms for multiple biomarkers detection were constructed by combining the ALP-regulated multicolor system with the well-developed aptasensor. The feasibility of the sensors was convincingly demonstrated by using thrombin and prostate specific antigen as model targets. In addition, the proposed multicolor strategy was employed for evaluating inhibition efficiency, and shows potential in visual screening of enzyme inhibitors. Such a facile, sensitive and low-cost sensing strategy provides a new perspective to develop universal platforms of point-of-care testing., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Autophagy and apoptosis, as major modes of cell death, play critical roles in cellular homeostasis. Our previous study demonstrated that the cross-talk between autophagy and apoptosis regulated cadmium-induced testicular injury and self-recovery, influencing male fertility. However, the underlying mechanism remains blurry. Herein, our subfertility rat model indicated that cadmium-induced autophagy and apoptosis were ameliorated by the activation of SIRT3 and blunted by the inhibition of SIRT3 in rat testis. Further, generating SIRT3 overexpression and knockdown models in TM3 mouse Leydig cells, we found that melatonin (SIRT3 activator) and overexpression of SIRT3 rescued cadmium-induced autophagy and apoptosis in TM3 cells. Knockdown of SIRT3 induced autophagy and apoptosis, which failed to be reversed by melatonin in TM3 cells. Taken together, SIRT3 functions as a pivotal protective factor in testicular Leydig cells injury, and melatonin regulates the cross-talk between autophagy and apoptosis by SIRT3, ameliorating cadmium-induced testicular injury., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Adipose tissue (AT), a critical endocrine gland, is capable of producing and secreting abundant adipokines. Adipokines act on distant or adjacent organ tissues via paracrine, autocrine, and endocrine mechanism, which play attractive roles in the regulation of glycolipid metabolism and inflammatory response. Increasing evidence shows that adipokines can connect obesity with cardiovascular diseases by serving as promoters or inhibitors in vascular calcification. The chronic hypoxia in AT, caused by the adipocyte hypertrophy, is able to trigger imbalanced adipokine generation, which leads to apoptosis, osteogenic differentiation of vascular smooth muscle cells (VSMCs), vascular inflammation, and abnormal deposition of calcium and phosphorus in the vessel wall. The objectives of this review aim at providing a brief summary of the crucial influence of major adipokines on the formation and development of vascular calcification, which may contribute to better understanding these adipokines for establishing the appropriate therapeutic strategies to counteract obesity-associated vascular calcification., (Copyright © 2021 Elsevier B.V. All rights reserved.)