PIII/PV-Catalyzed Beckmann Reaction and Sequential [2,3]-Sigmatropic Rearrangement to Construct 2-Amidopyridines.

An organophosphorus catalytic method for the synthesis of substituted 2-amidopyridines is reported. The method employs a small-ring organophosphorus-based catalyst and a hydrosilane reductant to drive the conversion of ketoximes and pyridine-N-oxides into 2-amidopyridines through sequential Beckmann rearrangement followed by [2,3]-sigmatropic rearrangement. The readily available ketoximes could be activated to nitrilium ions in PIII/PV redox catalysis and could efficiently participate in the domino reaction of pyridine-N-oxides, thus providing various substituted 2-amidopyridines in moderate to excellent yields. This presented strategy features excellent functional group tolerance and a broad substrate scope.

Enrofloxacin exposure undermines gut health and disrupts neurotransmitters along the microbiota-gut-brain axis in zebrafish.

The environmental prevalence of antibiotic residues poses a potential threat to gut health and may thereby disrupt brain function through the microbiota-gut-brain axis. However, little is currently known about the impacts of antibiotics on gut health and neurotransmitters along the microbiota-gut-brain axis in fish species. Taking enrofloxacin (ENR) as a representative, the impacts of antibiotic exposure on the gut structural integrity, intestinal microenvironment, and neurotransmitters along the microbiota-gut-brain axis were evaluated in zebrafish in this study. Data obtained demonstrated that exposure of zebrafish to 28-day environmentally realistic levels of ENR (6 and 60 µg/L) generally resulted in marked elevation of two intestinal integrity biomarkers (diamine oxidase (DAO) and malondialdehyde (MDA), upregulation of genes that encode inter-epithelial tight junction proteins, and histological alterations in gut as well as increase of lipopolysaccharide (LPS) in plasma, indicating an evident impairment of the structural integrity of gut. Moreover, in addition to significantly altered neurotransmitters, markedly higher levels of LPS while less amount of two short-chain fatty acids (SCFAs), namely acetic acid and valeric acid, were detected in the gut of ENR-exposed zebrafish, suggesting a disruption of gut microenvironment upon ENR exposure. Along with corresponding changes detected in gut, significant disruption of neurotransmitters in brain indicated by marked alterations in the contents of neurotransmitters, the activity of acetylcholin esterase (AChE), and the expression of neurotransmitter-related genes were also observed. These findings suggest exposure to environmental antibiotic residues may impair gut health and disrupt neurotransmitters along the microbiota-gut-brain axis in zebrafish. Considering the prevalence of antibiotic residues in environments and the high homology of zebrafish to other vertebrates including human, the risk of antibiotic exposure to the health of wild animals as well as human deserves more attention.

Microplastics weaken the exoskeletal mechanical properties of Pacific whiteleg shrimp Litopenaeus vannamei.

The ubiquitous presence of microplastics (MPs) in aquatic environments poses a significant threat to crustaceans. Although exoskeleton quality is critical for crustacean survival, the impact of MPs on crustacean exoskeletons remains elusive. Our study represents a pioneering effort to characterize the effects of MPs exposure on crustacean exoskeletons. In this study, the mechanical properties of whiteleg shrimp Litopenaeus vannamei exoskeletons were analyzed after exposure to environmentally realistic levels of MPs. Nanoindentation data demonstrated that MPs exposure significantly increased the hardness and modulus of both the carapace and abdominal segments of L. vannamei. Moreover, fractures and embedded MPs were detected on the exoskeleton surface using SEM-EDS analysis. Further analysis demonstrated that the degree of chitin acetylation (DA) in the shrimp exoskeleton, as indicated by FTIR peaks, was reduced by MPs exposure. In addition, exposure to MPs significantly inhibited the muscle Ca2+-ATPase activity and hemolymph calcium levels. Transcriptome and metabolome analyses revealed that the expression levels of genes encoding key enzymes and metabolites in the chitin biosynthetic pathway were significantly affected by MPs exposure. In conclusion, MPs at environmentally relevant concentrations may affect the exoskeletal mechanical properties of L. vannamei through a comprehensive mechanism involving the disruption of the crystalline structure of chitin, assimilation into the exoskeleton, and dysregulation of exoskeleton biosynthesis-related pathways.

A C-type lectin with a single carbohydrate-recognition domain (CRD) containing unique QPN/WDD motifs from Tegillarca granosa is involved in the innate immune defense.

C-type lectins (CTLs), a superfamily of Ca2+-dependent carbohydrate-recognition proteins, serve as pattern recognition receptors (PRRs) in the immune response of many species. However, little is currently known about the CTLs of the commercially and ecologically important bivalve species, blood clam (Tegillarca granosa). In this study, a CTL (designated as TgCTL-1) with a single carbohydrate-recognition domain (CRD) containing unique QPN/WDD motifs was identified in the blood clam through transcriptome and whole-genome searching. Multiple alignment and phylogenetic analysis strongly suggested that TgCTL-1 was a new member of the CTL superfamily. Expression analysis demonstrated that TgCTL-1 was highly expressed in the hemocytes and visceral mass of the clam under normal condition. In addition, the expression of TgCTL-1 was shown to be significantly up-regulated upon pathogen challenge. Moreover, the recombinant TgCTL-1 (rTgCTL-1) displayed agglutinating and binding activities against both the gram-positive and gram-negative bacteria tested in a Ca2+-dependent manner. Furthermore, it was found that the in vitro phagocytic activity of hemocytes was significantly enhanced by rTgCTL-1. In general, our results showed that TgCTL-1 was an inducible acute-phase secretory protein, playing crucial roles in recognizing, agglutinating, and binding to pathogenic bacteria as well as modulating phagocytic activity of hemocytes in the innate immune defense of blood clam.

Exposure to Polystyrene Nanoplastics Led to Learning and Memory Deficits in Zebrafish by Inducing Oxidative Damage and Aggravating Brain Aging.

Nanoplastics (NPs) may pass through the blood-brain barrier, giving rise to serious concerns about their potential toxicity to the brain. In this study, the effects of NPs exposure on learning and memory, the primary cognitive functions of the brain, are assessed in zebrafish with classic T-maze exploration tasks. Additionally, to reveal potential affecting mechanisms, the impacts of NPs exposure on brain aging, oxidative damage, energy provision, and the cell cycle are evaluated. The results demonstrate that NP-exposed zebrafish takes significantly longer for their first entry and spends markedly less time in the reward zone in the T-maze task, indicating the occurrence of learning and memory deficits. Moreover, higher levels of aging markers (ß-galactosidase and lipofuscin) are detected in the brains of NP-exposed fish. Along with the accumulation of reactive free radicals, NP-exposed zebrafish suffer significant levels of brain oxidative damage. Furthermore, lower levels of Adenosine triphosphate (ATP) and cyclin-dependent kinase 2 and higher levels of p53 are observed in the brains of NP-exposed zebrafish, suggesting that NPs exposure also results in a shortage of energy supply and an arrestment of the cell cycle. These findings suggest that NPs exposure may pose a severe threat to brain health, which deserves closer attention.

Toxic effects of four emerging pollutants on cardiac performance and associated physiological parameters of the thick-shell mussel (Mytilus coruscus).

Robust cardiac performance is critical for the health and even survival of an animal; however, it is sensitive to environmental stressors. At present, little is known about the cardiotoxicity of emerging pollutants to bivalve mollusks. Thus, in this study, the cardiotoxic effects of four emergent pollutants, carbamazepine (CBZ), bisphenol A (BPA), tetrabromobisphenol A (TBBPA), and tris(2-chloroethyl) phosphate (TCEP), on the thick-shell mussel, Mytilus coruscus, were evaluated by heartbeat monitoring and histological examinations. In addition, the impacts of these pollutants on parameters that closely related to cardiac function including neurotransmitters, calcium homeostasis, energy supply, and oxidative status were assessed. Our results demonstrated that 28-day exposure of the thick-shell mussel to these pollutants resulted in evident heart tissue lesions (indicated by hemocyte infiltration and myocardial fibrosis) and disruptions of cardiac performance (characterized by bradyrhythmia and arrhythmia). In addition to obstructing neurotransmitters and calcium homeostasis, exposure to pollutants also led to constrained energy supply and induced oxidative stress in mussel hearts. These findings indicate that although do differ somehow in their effects, these four pollutants may exert cardiotoxic impacts on mussels, which could pose severe threats to this important species and therefore deserves more attention.

Tris(2-chloroethyl) Phosphate Exerts Hepatotoxic Impacts on Zebrafish by Disrupting Hypothalamic-Pituitary-Thyroid and Gut-Liver Axes.

The ubiquitous environmental presence of tris(2-chloroethyl) phosphate (TCEP) poses a potential threat to animals; however, little is known about its hepatotoxicity. In this study, the effects of TCEP exposure (0.5 and 5.0 µg/L for 28 days) on liver health and the potential underlying toxification mechanisms were investigated in zebrafish. Our results demonstrated that TCEP exposure led to hepatic tissue lesions and resulted in significant alterations in liver-injury-specific markers. Moreover, TCEP-exposed fish had significantly lower levels of thyrotropin-releasing hormone and thyroid-stimulating hormone in the brain, evidently less triiodothyronine whereas more thyroxine in plasma, and markedly altered expressions of genes from the hypothalamic-pituitary-thyroid (HPT) axis in the brain or liver. In addition, a significantly higher proportion of Bacteroidetes in the gut microbiota, an elevated bacterial source endotoxin lipopolysaccharide (LPS) in the plasma, upregulated expression of LPS-binding protein and Toll-like receptor 4 in the liver, and higher levels of proinflammatory cytokines in the liver were detected in TCEP-exposed zebrafish. Furthermore, TCEP-exposed fish also suffered severe oxidative damage, possibly due to disruption of the antioxidant system. These findings suggest that TCEP may exert hepatotoxic effects on zebrafish by disrupting the HPT and gut-liver axes and thereafter inducing hepatic inflammation and oxidative stress.

Toxicity of microplastics and triclosan, alone and in combination, to the fertilisation success of a broadcast spawning bivalve Tegillarca granosa.

Since most marine invertebrates adopted external fertilisation, their fertilisation process is particularly vulnerable to aquatic pollutants. Both antimicrobial ingredients and microplastics (MPs) are ubiquitous in aquatic environments; however, their synergistic effects on the fertilisation of marine invertebrates remain unclear. Therefore, in this study, the fertilisation toxicity of MPs and triclosan (TCS), alone and in combination, was investigated in the broadcast spawning bivalve Tegillarca granosa. Results showed that MPs and TCS significantly suppressed the fertilisation success of T. granosa. As the fertilisation success of broadcast spawning invertebrates depends on successful gamete collisions, gamete fusion, and egg activation, sperm swimming velocity, viability, gamete collision probability, ATP status, and ion-transport enzyme activities were also analysed to further ascertain the underlying toxicity mechanisms. In summary, our findings indicate that the presence of MPs may enhance the fertilisation toxicity of TCS by hampering sperm-egg collision probability, reducing gamete fusion efficiency, and restricting Ca2+ oscillation formation.

Nobiletin attenuates monocrotaline-induced pulmonary arterial hypertension through PI3K/Akt/STAT3 pathway.

OBJECTIVES: Nobiletin is a flavonoid found in the peel of Citrus sinensis (oranges). The purpose of this study is to investigate whether Nobiletin can alleviate the monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and explore the underlying mechanisms. METHODS: The PAH rat model was replicated by subcutaneous injection of MCT. Nobiletin (1, 5 and 10 mg/kg) was administered by gavage from day 1 to day 21. After 21 days of MCT injection, the mean pulmonary artery pressure, pulmonary vascular resistance, Fulton Index, pulmonary artery remodelling, blood routine parameters, liver and kidney functions was measured. The level of inflammatory cytokines and PI3K/Akt/STAT3 were detected by qPCR, ELISA and western blot, the proliferation of pulmonary artery smooth muscle cells (PASMCs) was evaluated by CCK-8. KEY FINDINGS: Nobiletin (10 mg/kg) inhibited the MCT-induced increase in mean pulmonary artery pressure and pulmonary vascular resistance, right ventricular hypertrophy and pulmonary artery remodelling in rats. Nobiletin decreased the levels of inflammatory cytokines and phosphorylation level of PI3K/Akt/STAT3 in lungs of MCT-treated rats. Nobiletin inhibited the proliferation and lowered the inflammatory cytokines level induced by PDGF-BB in PASMCs. CONCLUSION: Nobiletin attenuates MCT-induced PAH, and the potential mechanism is to inhibit inflammation through PI3K/Akt/STAT3 pathway.

Research and Application of Medical Polyetheretherketone as Bone Repair Material.

Polyetheretherketone (PEEK) can potentially be used for bone repair because its elastic modulus is similar to that of human natural bone and good biocompatibility and chemical stability. However, its hydrophobicity and biological inertness limit its application in the biomedical field. Inspired by the composition, structure, and function of bone tissue, many strategies are proposed to change the structure and functionality of the PEEK surface. In this review, the applications of PEEK in bone repair and the optimization strategy for PEEK's biological activity are reviewed, which provides a direction for the development of multifunctional bone repair materials in the future.

Animal models of cancer metastasis to the bone.

Cancer metastasis is a major cause of mortality from several tumors, including those of the breast, prostate, and the thyroid gland. Since bone tissue is one of the most common sites of metastasis, the treatment of bone metastases is crucial for the cure of cancer. Hence, disease models must be developed to understand the process of bone metastasis in order to devise therapies for it. Several translational models of different bone metastatic tumors have been developed, including animal models, cell line injection models, bone implant models, and patient-derived xenograft models. However, a compendium on different bone metastatic cancers is currently not available. Here, we have compiled several animal models derived from current experiments on bone metastasis, mostly involving breast and prostate cancer, to improve the development of preclinical models and promote the treatment of bone metastasis.

Clinical efficacy of customized modular prosthesis in the treatment of femoral shaft metastases.

Purpose: To examine clinical outcomes of a specialized modular prosthesis used to fill a bone deficiency following removal of femoral shaft metastases. Methods: Eighteen patients with femoral shaft metastases who underwent en bloc resection and implantation of a personalized modular prosthesis between December 2014 and December 2019 were retrospectively analyzed. Pain, limb function, and quality of life were evaluated using the visual analog scale (VAS), Musculoskeletal Tumor Society (MSTS) scale, International Society of Limb Salvage (ISOLS) scoring system, Karnofsky Performance Status (KPS) scale, and Nottingham Health Profile (NHP) scale. The Kaplan-Meier technique was used to analyze patient survival. Results: The operation duration was 90-150 min (mean, 115 min), and the osteotomy length was 9-16 cm (mean, 11.72 cm). The patients were followed for 12-62 months (mean, 25.28 months). The VAS and NHP ratings were lower at 3, 6, and 12 months after surgery than before surgery, while the MSTS, ISOLS, and KPS scores were higher after surgery than they had been before. These differences were statistically significant (P<0.05). The survival period was between 7 and 62 months (mean, 20.89 months), and the rates of survival at 1-year and 2-year were 72.22% and 27.78%, respectively. Except for two patients with aseptic prosthesis loosening during the follow-up period, there were no problems. Conclusion: En bloc excision and implantation of a personalized modular prosthesis can reduce pain and improve the ability of patients with femoral shaft metastases to perform daily activities, thereby improving their quality of life.

Toxicities of polystyrene microplastics (MPs) and hexabromocyclododecane (HBCD), alone or in combination, to the hepatopancreas of the whiteleg shrimp, Litopenaeus vannamei.

The hepatopancreas is one of the largest organs playing crucial roles in metabolism and detoxification in crustacean invertebrates. Although toxicities have been increasingly documented for the two ubiquitous pollutants, hexabromocyclododecane (HBCD) and microplastics (MPs), in model animals, little is known about their impacts on the hepatopancreas of crustaceans. To fill this knowledge gap, the effects of MPs and HBCD, alone or in combination, on the hepatopancreas were evaluated in a commercially important crustacean species (the whiteleg shrimp) by histological observation as well as quantification of hepatic lesion-, metabolism-, and detoxification-related parameters. In addition, to reveal potential mechanisms underlying the hepatoxicity observed, the accumulation of HBCD in the shrimp and the status of oxidative stress were also investigated. Our results demonstrated that exposure of the whiteleg shrimp to MPs and HBCD for 4 weeks resulted in evident histological injury in the hepatopancreas and marked elevation in hepatic lesion markers (alanine aminotransferase and aspartate aminotransferase) in the hemolymph. Moreover, both metabolism (activity of phosphofructokinase, contents of lactic acid and adenosine triphosphate, and expression of metabolism-related genes) and detoxification (contents of cytochrome P450, UDP-glucuronosyltransferase, and glutathione, activity of glutathione S-transferase, and expression of detoxification-related genes) were found to be disrupted by the pollutants tested. In addition, exposure to MPs and HBCD also led to alterations in the contents and/or activities of antioxidant enzymes and resulted in oxidative damage to the hepatopancreas (indicated by marked elevation in malondialdehyde content). Furthermore, a significant amount of HBCD accumulated in shrimp treated with HBCD-containing seawater. The data also illustrated that HBCD-MP coexposure was more toxic than single exposure to these pollutants. These findings suggest that MPs and HBCD may exert hepatotoxic impacts on whiteleg shrimp by accumulating in vivo and inducing oxidative stress, which could pose a severe threat to the health of this important crustacean species.

Assessment of Nonalcoholic Fatty Liver Disease Symptoms and Gut-Liver Axis Status in Zebrafish after Exposure to Polystyrene Microplastics and Oxytetracycline, Alone and in Combination.

BACKGROUND: Environmental pollution may give rise to the incidence and progression of nonalcoholic fatty liver disease (NAFLD), the most common cause for chronic severe liver lesions. Although knowledge of NAFLD pathogenesis is particularly important for the development of effective prevention, the relationship between NAFLD occurrence and exposure to emerging pollutants, such as microplastics (MPs) and antibiotic residues, awaits assessment. OBJECTIVES: This study aimed to evaluate the toxicity of MPs and antibiotic residues related to NAFLD occurrence using the zebrafish model species. METHODS: Taking common polystyrene MPs and oxytetracycline (OTC) as representatives, typical NAFLD symptoms, including lipid accumulation, liver inflammation, and hepatic oxidative stress, were screened after 28-d exposure to environmentally realistic concentrations of MPs (0.69mg/L) and antibiotic residue (3.00µg/L). The impacts of MPs and OTC on gut health, the gut-liver axis, and hepatic lipid metabolism were also investigated to reveal potential affecting mechanisms underpinning the NAFLD symptoms observed. RESULTS: Compared with the control fish, zebrafish exposed to MPs and OTC exhibited significantly higher levels of lipid accumulation, triglycerides, and cholesterol contents, as well as inflammation, in conjunction with oxidative stress in their livers. In addition, a markedly smaller proportion of Proteobacteria and higher ratios of Firmicutes/Bacteroidetes were detected by microbiome analysis of gut contents in treated samples. After the exposures, the zebrafish also experienced intestinal oxidative injury and yielded significantly fewer numbers of goblet cells. Markedly higher levels of the intestinal bacteria-sourced endotoxin lipopolysaccharide (LPS) were also detected in serum. Animals treated with MPs and OTC exhibited higher expression levels of LPS binding receptor (LBP) and downstream inflammation-related genes while also exhibiting lower activity and gene expression of lipase. Furthermore, MP-OTC coexposure generally exerted more severe effects compared with single MP or OTC exposure. DISCUSSION: Our results suggested that exposure to MPs and OTC may disrupt the gut-liver axis and be associated with NAFLD occurrence. https://doi.org/10.1289/EHP11600.

Clinical effect of surgical resection on primary malignant and invasive bone tumours of the proximal fibula.

There is no unified surgical plan for fibular proximal malignant tumours; therefore, the present study retrospectively analysed the medical records of 19 patients with primary malignant and invasive tumours in the proximal fibula and discussed the postoperative oncological results, complications and postoperative functions of limb salvage surgery. According to pathological classification, there were 10 osteosarcoma cases, 3 chondrosarcoma cases, 2 invasive giant cell osteosarcoma tumour cases, 1 epithelioid sarcoma case, 1 leiomyosarcoma case, 1 fibrosarcoma case and 1 lymphoma case. According to the Enneking instalment, IB stage was found in 2 cases, IIA in 2 cases and IIB in 15 cases. A total of 3 patients underwent Malawer I resection, and 16 patients underwent Malawer II resection. The follow-up period was 11-174 months, with an average of 76.58 months. Local recurrence occurred in three patients and distant metastasis in seven patients; 4 patients succumbed and 15 survived. After biceps femoris tendon reconstruction and lateral collateral ligament insertion, 18 patients had good knee stability. The Musculoskeletal Tumour Society scale ranged between 23 and 29 points, with an average of 27.26 points; the Lysholm Knee Score was 65-84 points, with an average of 83 points. After the resection of proximal fibula primary and invasive tumours, the biceps femoris tendon and lateral collateral ligament insertion point was reconstructed. The data show that this technique can effectively reconstruct stability and restore knee function.

Gamma-aminobutyric acid (GABA) suppresses hemocyte phagocytosis by binding to GABA receptors and modulating corresponding downstream pathways in blood clam, Tegillarca granosa.

Although accumulating data demonstrated that gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, plays an important regulatory role in immunity of vertebrates, its immunomodulatory function and mechanisms of action remain poorly understood in invertebrates such as bivalve mollusks. In this study, the effect of GABA on phagocytic activity of hemocytes was evaluated in a commercial bivalve species, Tegillarca granosa. Furthermore, the potential regulatory mechanism underpinning was investigated by assessing potential downstream targets. Data obtained demonstrated that in vitro GABA incubation significantly constrained the phagocytic activity of hemocytes. In addition, the GABA-induced suppression of phagocytosis was markedly relieved by blocking of GABAA and GABAB receptors using corresponding antagonists. Hemocytes incubated with lipopolysaccharides (LPS) and GABA had significant higher K+-Cl- cotransporter 2 (KCC2) content compared to the control. In addition, GABA treatment led to an elevation in intracellular Cl-, which was shown to be leveled down to normal by blocking the ionotropic GABAA receptor. Treatment with GABAA receptor antagonist also rescued the suppression of GABAA receptor-associated protein (GABARAP), KCC, TNF receptor associated factor 6 (TRAF6), inhibitor of nuclear factor kappa-B kinase subunit alpha (IKKα), and nuclear factor kappa B subunit 1 (NFκB) caused by GABA incubation. Furthermore, incubation of hemocytes with GABA resulted in a decrease in cAMP content, an increase in intracellular Ca2+, and downregulation of cAMP-dependent protein kinase (PKA), calmodulin kinase II (CAMK2), calmodulin (CaM), calcineurin (CaN), TRAF6, IKKα, and NFκB. All these above-mentioned changes were found to be evidently relieved by blocking the metabotropic G-protein-coupled GABAB receptor. Our results suggest GABA may play an inhibitory role on phagocytosis through binding to both GABAA and GABAB receptors, and subsequently regulating corresponding downstream pathways in bivalve invertebrates.

Enrofloxacin exposure induces anxiety-like behavioral responses in zebrafish by affecting the microbiota-gut-brain axis.

The ubiquitous presence of antibiotic residues in aqueous environments poses a great potential threat to aquatic organisms. Nevertheless, the behavioral effects of environmentally realistic levels of antibiotics remain poorly understood in fish species. In this study, the behavioral impacts of enrofloxacin, one of typical fluoroquinolone antibiotics that is frequently detected in aquatic environments, were evaluated by the classic light-dark test (LDT) and novel tank task (NTT) in zebrafish. Furthermore, the effects of enrofloxacin exposure on the microbiota-gut-brain axis were also assessed to reveal potential affecting mechanisms underlying the behavioral abnormality observed. Our results demonstrated that zebrafish exposed to 60 µg/L enrofloxacin for 28 days took significantly longer to enter the stressful area of the testing tank and spent significantly less time there in both the LDT and NTT, indicating abnormal anxiety-like behaviors induced by the exposure. In addition, exposure to enrofloxacin at 6 and 60 µg/L resulted in a significant elevation in Bacteroidetes and a marked decline in the Firmicutes/Bacteroidetes ratio of the gut microbiota. Moreover, the intestinal contents of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), glucagon-like peptide 1 (GLP-1), and 5-hydroxytryptamine (5-HT) in zebrafish were significantly upregulated, whereas those of plasma adrenocorticotropic hormone (ACTH) and cortisol (COR) were markedly downregulated upon enrofloxacin exposure. Incubation of zebrafish with a high dose of enrofloxacin (60 µg/L) also resulted in evident increases in the contents of corticotropin-releasing hormone (CRH), brain-derived neurotrophic factor (BDNF), and neuropeptide Y (NPY) in the brain. Fortunately, no significant alteration in the expression of glial fibrillary acidic protein (GFAP) was detected in the brain after enrofloxacin exposure. Our findings suggest that the disruption of the microbiota-gut-brain axis may account for enrofloxacin-induced anxiety-like behaviors in zebrafish. Since the disruption of microbiota-gut-brain axis may give rise to various clinical symptoms, the health risk of antibiotic exposure deserves more attention.

Size-Selective Suzuki-Miyaura Coupling Reaction over Ultrafine Pd Nanocatalysts in a Water-Stable Indium-Organic Framework.

Metal nanoparticles stabilized by crystalline metal-organic frameworks (MOFs) are highly promising for green heterogeneous catalysis. In this work, in situ formed ultrafine Pd nanocatalysts with an average size of 3.14 nm have been successfully immobilized into the mesopores or defects of a water-stable indium-based MOF by the double-solvent method and subsequent reduction. Significantly, the obtained Pd@InOF-1 displays an obvious and satisfactory size-selective effect in the Suzuki-Miyaura coupling reaction between arylboronic acids and aryl bromides. On the basis of the synergistic effect, microporous InOF-1 nanorods afford a confined space for improving the selectivity of target products while Pd nanoparticles endow abundant active sites for catalysis. Herein, choosing the smallest size reactant with only one benzene ring gives the highest isolated yield of 90%, and if the size is larger, the yield is obviously reduced or even the target product could not be collected. Looking forward, this demonstrated study not only assembles a well-designed Pd@MOF composite with unique micro-nanostructures but also delivers an impressive option for cross-coupling reaction, which has implications for the further development of MOF hybrids for sustainable applications.

Three-dimensional-printed titanium prostheses with bone trabeculae enable mechanical-biological reconstruction after resection of bone tumours.

Reconstruction after resection has always been an urgent problem in the treatment of bone tumours. There are many methods that can be used to reconstruct bone defects; however, there are also many complications, and it is difficult to develop a safe and effective reconstruction plan for the treatment of bone tumours. With the rapid development of digital orthopaedics, three-dimensional printing technology can solve this problem. The three-dimensional printing of personalised prostheses has many advantages. It can be used to print complex structures that are difficult to fabricate using traditional processes and overcome the problems of stress shielding and low biological activity of conventional prostheses. In this study, 12 patients with bone tumours were selected as research subjects, and based on individualised reverse-engineering design technology, a three-dimensional model of each prosthesis was designed and installed using medical image data. Ti6Al4V was used as the raw material to prepare the prostheses, which were used to repair bone defects after surgical resection. The operation time was 266.43 ± 21.08 minutes (range 180-390 minutes), and intraoperative blood loss was 857.26 ± 84.28 mL (range 800-2500 mL). One patient had delayed wound healing after surgery, but all patients survived without local tumour recurrence, and no tumour metastasis was found. No aseptic loosening or structural fracture of the prosthesis, and no non-mechanical prosthesis failure caused by infection, tumour recurrence, or progression was observed. The Musculo-Skeletal Tumour Society (MSTS) score of limb function was 22.53 ± 2.09 (range 16-26), and ten of the 12 patients scored ≥ 20 and were able to function normally. The results showed that three-dimensional printed prostheses with an individualised design can achieve satisfactory short-term clinical efficacy in the reconstruction of large bone defects after bone tumour resection.

Impacts of microplastics and carbamazepine on the shell formation of thick-shell mussels and the underlying mechanisms of action.

Forming calcareous exoskeletons is crucial for the health and survival of calcifiers such as bivalves. However, the impacts of waterborne emergent pollutants on this important process remain largely unknown. In this study, the effects of two types of emergent pollutants, microplastics (MPs) and carbamazepine (CBZ), which are ubiquitously present in ocean environments, on shell formation were assessed in the thick-shell mussel (Mytilus coruscus) with a shell regeneration experiment. In addition, their impacts on the in vivo contents of ATP, Ca2+, carbonic anhydrase (CA), and bone morphogenetic protein receptor type-2 (BMPR2), the activity of phosphofructokinase (PFK) and Ca2+-ATPase, and the expression of shell-formation related genes were analyzed. The data collected demonstrated that shell regeneration after mechanical injury was significantly arrested by CBZ and/or MPs. Besides, all the physiological and molecular parameters investigated were markedly suppressed by these two pollutants. Furthermore, synergistic impacts on most of the parameters examined were observed between CBZ and MPs. Our results indicate that these two pollutants may disrupt shell formation by constraining the availability of raw materials and energy, inhibiting the formation of the organic shell matrix, and interfering with the regulation of crystallization, which may have far-reaching impacts on the health of marine calcifiers.