Taurocholic acid represents an earlier and more sensitive biomarker and promotes cholestatic hepatotoxicity in ANIT-treated rats.

Bile acid homeostasis is crucial for the normal physiological functioning of the liver. Disruptions in bile acid profiles are closely linked to the occurrence of cholestatic liver injury. As part of our diagnostic and therapeutic approach, we aimed to investigate the disturbance in bile acid profiles during cholestasis and its correlation with cholestatic liver injury. Before the occurrence of liver injury, alterations in bile acid profiles were detected in both plasma and liver between 8 and 16 h, persisting up to 96 h. TCA, TCDCA, and TUDCA in the plasma, as well as TCA, TUDCA, TCDCA, TDCA, TLCA, and THDCA in the liver, emerged as early sensitive and potential markers for diagnosing ANIT-induced cholestasis at 8-16 h. The distinguishing features of ANIT-induced liver injury were as follows: T-BAs exceeding G-BAs and serum biochemical indicators surpassing free bile acids. Notably, plasma T-BAs, particularly TCA, exhibited higher sensitivity to cholestatic hepatotoxicity compared with serum enzyme activity and liver histopathology. Further investigation revealed that TCA exacerbated ANIT-induced liver injury by elevating liver function enzyme activity, inflammation, and bile duct proliferation and promoting the migration of bile duct epithelial cell. Nevertheless, no morphological changes or alterations in transaminase activity indicative of liver damage were observed in the rats treated with TCA alone. Additionally, there were no changes in bile acid profiles or inflammatory responses under physiological conditions with maintained bile acid homeostasis. In summary, our findings suggest that taurine-conjugated bile acids in both plasma and liver, particularly TCA, can serve as early and sensitive markers for predicting intrahepatic cholestatic drugs and can act as potent exacerbators of cholestatic liver injury progression. However, exogenous TCA does not induce liver injury under physiological conditions where bile acid homeostasis is maintained.

Characterization of dental dust particles and their pathogenicity to respiratory system: a narrative review.

OBJECTIVES: Dental professionals are exposed to large amounts of dust particles during routine treatment and denture processing. This article provides a narrative review to investigate the most prevalent dust-related respiratory diseases among dental professionals and to discuss the effects of dental dust on human respiratory health. MATERIALS AND METHODS: A literature search was performed in PubMed/Medline, Web of Science, and Embase for articles published between 1990 and 2022. Any articles on the occupational respiratory health effects of dental dust were included. RESULTS: The characterization and toxicity evaluation of dental dust show a correlation between dust exposure and respiratory system injury, and the possible pathogenic mechanism of dust is to cause lung injury and abnormal repair processes. The combination use of personal protective equipment and particle removal devices can effectively reduce the adverse health effects of dust exposure. CONCLUSIONS: Dental dust should be considered an additional occupational hazard in dental practice. However, clinical data and scientific evidence on this topic are still scarce. Further research is required to quantify dust in the dental work environment and clarify its pathogenicity and potential toxicological pathways. Nonetheless, the prevention of dust exposure should become a consensus among dental practitioners. CLINICAL RELEVANCE: This review provides dental practitioners with a comprehensive understanding and preventive advice on respiratory health problems associated with dust exposure.

Grain Boundary Engineering with Self-Assembled Porphyrin Supramolecules for Highly Efficient Large-Area Perovskite Photovoltaics.

Grain boundary management is critical to the performance and stability of polycrystalline perovskite solar cells (PSCs), especially large-area devices. However, typical passivators are insulating in nature and limit carrier transport. Here, we design a supramolecular binder for grain boundaries to simultaneously passivate defects and promote hole transport across perovskite grain boundaries. By doping the monoamine porphyrins (MPs, M = Co, Ni, Cu, Zn, or H) into perovskite films, MPs self-assemble into supramolecules at grain boundaries. Organic cations in perovskites protonate MPs in supramolecules to form ammonium porphyrins bound on the perovskite grain surface, to passivate defects and extract holes from the perovskite lattice. Periodic polarons in supramolecules (especially NiP-supramolecule) promote the transport of extracted holes across boundaries, reducing nonradiative carrier recombination. The NiP-doped PSCs reveal a certified efficiency of 22.1% for an active area of 1.0 cm2 with the remarkably improved open-circuit voltage and fill factor. The unencapsulated device retained over 80% initial performance under AM 1.5G solar light continuous illumination or heating at 85 °C over 3000 h.

Evaluation of the safety and protection efficacy of an attenuated genotype vii newcastle disease virus strain as a candidate vaccine.

Newcastle disease (ND) is a serious avian infectious disease, causing severe economic loss worldwide. Its prevention depends on comprehensive vaccination scheme against Newcastle disease virus (NDV). However, current vaccine strains are of different genotypes with prevalent circulating strains (genotype VII), with significant genetic distance. Our team previously generated a genotype matched attenuated NDV strain (rmNA-1). In this study, its safety and immunization efficacy were evaluated. Its lentogenic characteristic was stable for 25 generations in embryonated chicken eggs and for six generations in SPF chickens. Overdosed administration did not cause any clinical signs or pathogenic changes in chickens. As to its immunization effect, rmNA-1 stimulated a comparable serum NDV specific antibody level to a LaSota (genotype II) strain based commercial vaccine, and provided full protection against virulent genotype VII strain challenge, with significantly reduced virus shedding period.

Scutellarein inhibits RANKL-induced osteoclast formation in vitro and prevents LPS-induced bone loss in vivo.

Osteoporosis, arthritis, Peget's disease, bone tumor, periprosthetic joint infection, and periprosthetic loosening have a common characteristic of osteolysis, which is characterized by the enhanced osteoclastic bone resorptive function. At present, the treatment target of these diseases is to interfere with osteoclastic formation and function. Scutellarein (Scu), a flavonoids compound, can inhibit the progress of tumor and inflammation. However, the role of Scu in inflammatory osteolysis isn't elucidated clearly. Our study showed that Scu inhibited bone destruction induced by LPS in vivo and OC morphology and function induced by RANKL in vitro. Mechanistic studies revealed that Scu suppressed osteoclastic marker gene expression by RANKL-induced, such as Ctsk9, Mmp9, Acp5, and Atp6v0d2. In addition, we found that the inhibition effects of osteoclastogenesis and bone resorption function of Scu were mediated via attenuating NF-κB and NFAT signaling pathways. In conclusion, the results showed that Scu may become a potential new drug for the treatment of inflammatory osteolysis.

Daphnetin attenuates LPS-induced osteolysis and RANKL mediated osteoclastogenesis through suppression of ERK and NFATc1 pathways.

Aseptic prosthetic loosening and periprosthetic infection resulting in inflammatory osteolysis is a leading complication of total joint arthroplasty (TJA). Excessive bone destruction around the bone and prosthesis interface plays a key role in the loosening prostheses leading to revision surgery. The bacterial endotoxins or implant-derived wear particles-induced inflammatory response is the major cause of the elevated osteoclast formation and activity. Thus, agents or compounds that can attenuate the inflammatory response and/or inhibit the elevated osteoclastogenesis and excessive bone resorption would provide a promising therapeutic avenue to prevent aseptic prosthetic loosening in TJA. Daphnetin (DAP), a natural coumarin derivative, is clinically used in Traditional Chinese Medicine for the treatment of rheumatoid arthritis due to its anti-inflammatory properties. In this study, we report for the first time that DAP could protect against lipopolysaccharide-induced inflammatory bone destruction in a murine calvarial osteolysis model in vivo. This protective effect of DAP can in part be attributed to its direct inhibitory effect on RANKL-induced osteoclast differentiation, fusion, and bone resorption in vitro. Biochemical analysis found that DAP inhibited the activation of the ERK and NFATc1 signaling cascades. Collectively, our findings suggest that DAP as a natural compound has potential for the treatment of inflammatory osteolysis.

Vx-11e protects against titanium-particle-induced osteolysis and osteoclastogenesis by supressing ERK activity.

Wear particle-induced osteolysis around the prosthesis is the most common long-term complication after total joint replacement surgery which often leads to aseptic loosening of the prosthesis. Osteoclasts play key roles in the osteolytic process. Currently there is a lack of clinically effective measures to prevent or treat peri-prosthetic osteolysis and thus identification of new agents that can inhibit the enhanced osteoclastic bone resorption is warranted. Through this study, we discovered that the specific and potent ERK1/2 inhibitor, Vx-11e, can protect against calvarial osteolysis caused by titanium (Ti) particles in vivo. Low doses of Vx-11e mildly reduced osteoclast resorption whilst no calvarial osteolysis was observed with high dose Vx-11e treatment. Histological examination showed fewer osteoclasts and reduced bone erosion in the Vx-11e treated groups. In vitro cellular analyses showed that Vx-11e inhibited osteoclast formation from BMM precursors in response to RANKL, as well as bone resorption by mature osteoclasts. Mechanistically, Vx-11e impaired RANKL-induced ERK1/2 signaling by inhibiting its kinase activity thereby blocking the phosphorylation of downstream substrates. Moreover, Vx-11e significantly reduced the expression of RANKL-mediated genes such as ACP5/TRAcP, CTR, MMP-9, CTSK. Collectively, our data provides evidence for the potential therapeutic use of Vx-11e for the treatment of osteolysis diseases caused by extremely actived osteoclastogenesis.

Detection of viral components in exosomes derived from NDV-infected DF-1 cells and their promoting ability in virus replication.

Exosomes are micro messengers encapsulating RNA, DNA, and proteins for intercellular communication associated with various physiological and pathological reactions. Several viral infection processes have been reported to pertain to exosomal pathways. However, because of the difficulty in obtaining avian-sourced exosomes, avian virus-related exosomes are scarcely investigated. In this study, we developed a protein A/G-correlated method and successfully obtained the Newcastle disease virus-related exosome (NDV Ex). These exosomes promoted NDV propagation, proven by both GW4869-mediated deprivation and exosomal supplementation. Viral structural proteins NP and F were detected in the NDV Ex and further investigation indicated that the NP protein can be transferred to DF-1 cells through exosomes. The intracellular NP protein exhibited viral replication-promoting and cytokine-suppressing abilities. Therefore, NDV infection produces exosomes, which transfer viral NP protein and promote NDV infection, emphasizing the importance of exosomes in an NDV infection.

Monocrotaline Suppresses RANKL-Induced Osteoclastogenesis In Vitro and Prevents LPS-Induced Bone Loss In Vivo.

BACKGROUND/AIMS: Extensive osteoclast formation plays a critical role in bone diseases, including rheumatoid arthritis, periodontitis and the aseptic loosening of orthopedic implants. Thus, identification of agents that can suppress osteoclast formation and bone resorption is important for the treatment of these diseases. Monocrotaline (Mon), the major bioactive component of crotalaria sessiliflora has been investigated for its anti-cancer activities. However, the effect of Mon on osteoclast formation and osteolysis is not known. METHODS: The bone marrow macrophages (BMMs) were cultured with M-CSF and RANKL followed by Mon treatment. Then the effects of Mon on osteoclast differentiation were evaluated by counting TRAP (+) multinucleated cells. Moreover, effects of Mon on hydroxyapatite resorption activity of mature osteoclast were studied through resorption areas measurement. The involved potential signaling pathways were analyzed by performed Western blotting and quantitative real-time PCR examination. Further, we established a mouse calvarial osteolysis model to measure the osteolysis suppressing effect of Mon in vivo. RESULTS: In this study, we show that Mon can inhibit RANKL-induced osteoclast formation and function in a dose-dependent manner. Mon inhibits the expression of osteoclast marker genes such as tartrate-resistant acid phosphatase (TRAP) and cathepsin K. Furthermore, Mon inhibits RANKL-induced the activation of p38 and JNK. Consistent with in vitro results, Mon exhibits protective effects in an in vivo mouse model of LPS-induced calvarial osteolysis. CONCLUSION: Taken together our data demonstrate that Mon may be a potential prophylactic anti-osteoclastic agent for the treatment of osteolytic diseases caused by excessive osteoclast formation and function.

Newcastle disease virus-like particles induce dendritic cell maturation and enhance viral-specific immune response.

Circulating of genotype VII Newcastle disease virus (NDV) is a great threat to the poultry industry worldwide. Virus-like particles (VLPs) are increasingly being considered as potential viral vaccines due to their safety and efficacy. In this study, we analyzed in vitro the stimulatory effects of VLPs containing the matrix and hemagglutinin-neuraminidase of genotype VII NDV on dendritic cells (DCs) and evaluated their immunogenicity in mice. The results showed that immature bone marrow-derived dendritic cells (BMDCs) responded to stimulation with VLPs by up-regulating expressions of MHC II, CD40, CD80, and CD86 molecules and by increasing the cytokine secretions of TNF-α, IFN-γ, IL-6, and IL-12p70. Besides, VLPs enhanced the immunostimulatory capacity of DCs to stimulate autologous T cell proliferation. Furthermore, VLPs can induce efficient humoral and cellular immune responses, and recruit mature DCs to the spleen in C57BL/6 mice, as shown by an obvious increase in double-positive proliferation of splenic CD11c+CD86+ cells. These data indicate that NDV VLPs can be a valuable candidate for NDV vaccine development.

The relationship between depression severity and heart rate variability in children and adolescents: A meta-analysis.

OBJECTIVE: Depression in children and adolescents has gradually attracted social attention. Heart rate variability (HRV) has been found to be influenced by depression severity, but results have not been uniformed in children and adolescents. This study investigated the relationship between depression severity and heart rate variability in children and adolescents, aiming to provide additional evidence for an objective, effective, and convenient depression screening tool in this population. METHODS: Literature searching was conducted in China National Knowledge Infrastructure (CNKI), Wanfang Data, Web of Science, PubMed, ScienceDirect, and EBSCO. Relevant studies investigating the relationship between depression severity and HRV in children and adolescents were selected for meta-analysis. RESULTS: 31 articles were included in this meta-analysis, involving 4534 participants. Depression severity in children and adolescents was significantly negatively correlated with high frequency (HF) and root mean square of successive differences (RMSSD) in HRV (HF: r = -0.10, 95% CI: -0.17 to -0.04, p = 0.001; RMSSD: r = -0.18, 95% CI: -0.30 to -0.05, p = 0.01). The relationship between HF and depression severity was moderated by age, higher among those aged >12 than among those aged <12 (r = -0.17, -0.02, Q = 7.32, p = 0.007). CONCLUSION: Heart rate variability is associated with depression severity in children and adolescents.

NDV inhibited IFN-ß secretion through impeding CHCHD10-mediated mitochondrial fusion to promote viral proliferation.

Newcastle disease virus (NDV) is an RNA virus that can promote its own replication through the inhibition of cellular mitochondrial fusion. The proteins involved in mitochondrial fusion, namely mitofusin 1 (Mfn1) and optic atrophy 1 (OPA1) are associated with interferon-beta (IFN-ß) secretion during NDV infection. However, the precise mechanism by which NDV modulates the Mfn1-mediated or OPA1-mediated fusion of mitochondria, thereby impacting IFN-ß, remains elusive. This study revealed that the downregulation of the mitochondrial protein known as coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) exerts a negative regulatory effect on OPA1 and Mfn1 in human lung adenocarcinoma (A549) cells during the late stage of NDV infection. This reduction in CHCHD10 expression impeded cellular mitochondrial fusion, subsequently leading to a decline in the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-κB), ultimately resulting in diminished secretion of IFN-ß. In contrast, the overexpression of CHCHD10 alleviated infection-induced detrimental effect in mitochondrial fusion, thereby impeding viral proliferation. In summary, NDV enhances its replication by inhibiting the CHCHD10 protein, which impedes mitochondrial fusion and suppresses IFN-ß production through the activation of IRF3 and NF-κB.

Mitochondrial protein CHCHD10 inhibits NDV replication and reduces pathological changes.

Newcastle disease (ND) is a disease that threatens the world's poultry industry, which is caused by virulent Newcastle disease virus (NDV). As its pathogenic mechanism remains not fully clear, the proteomics of NDV-infected cells were analyzed. The results revealed that coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) protein displayed a significant decrease at the late stage of NDV infection. To investigate the function of CHCHD10 in NDV infection, its expression after NDV infection was detected both in vivo and in vitro. Besides, the tissue viral loads and pathological damage of C57BL/6 mice with CHCHD10 differently expressed were also investigated. The results showed that the CHCHD10 expression was significantly decreased both in vivo and in vitro at the late stage of NDV infection. The viral loads were significantly higher in CHCHD10 silenced C57BL/6 mice, along with more severe pathological damage and vice versa.

Effect of co-infection with Newcastle disease virus on Mycoplasma gallisepticum pathogenesis in vivo and in vitro.

The co-infection of Newcastle disease virus (NDV) and Mycoplasma gallisepticum (MG) has a detrimental effect on chicken production performance, exerts a deleterious impact on poultry production performance, resulting in substantial economic losses. However, the exact impact and underlying mechanisms remain ambiguous. In this study, co-infection models were established both in vivo and in vitro. Through these models, it was found that the co-infection facilitated the replication of MG and NDV, as well as MG induced pathogenesis. The administration of lentogenic NDV resulted in the suppression of the innate immune response in vivo. At cellular level, co-infection promoted MG induced apoptosis through caspase-dependent mitochondrial endogenous pathway and suppressed the inflammatory secretion. This research contributes novel insights in co-infection.

Mineralogical transformation of arsenic at different copper smelting workshops: The impact on arsenic bioaccessibility.

Soil arsenic (As) contamination associated with the demolition of smelting plants has received increasing attention. Soil As can source from different industrial processes, and also participate in soil weathering, making its speciation rather complex. This study combined the usage of chemical sequential extraction and advanced spectroscopic techniques, e.g., time of flight secondary ion mass spectrometry (ToF-SIMS), to investigate the mineralogical transformation of soil As at different processing sites from a typical copper smelting plant in China. Results showed that the stability of arsenic species decreased following the processes of storage, smelting, and flue gas treatment. Arsenic in the warehouse area was incorporated into pyrite (FeS2) as well as its secondary minerals such as jarosite (KFe3(SO4)2(OH)6). At the smelting area, a large proportion of As was adsorbed by iron oxides from smelting slags, while some As existed in stable forms like orpiment (As2S3). At the acid-making area, more than half of As was adsorbed on amorphous iron oxides, and some were adsorbed on the flue gas desulfurization gypsum. More importantly, over 86% of the As belonged to non-specifically and specifically adsorbed fractions was found to be bioaccessible, highlighting the gypsum-adsorbed As one of the most hazardous species in smelting plant soils. Our findings indicated the importance of iron oxides in As retention and suggested the potential health risk of gypsum-adsorbed As. Such detailed knowledge of As speciation and bioaccessibility is vital for the management and remediation of As-contaminated soils in smelting plants.

Protective effects of a novel chimeric virus-like particle vaccine against virulent NDV and IBDV challenge.

Newcastle disease (ND) and infectious bursal disease (IBD) pose significant threats to the chicken industry, causing substantial economic losses. Currently, immunization through vaccination is the most effective strategy to prevent ND and IBD but currently used traditional vaccines, including inactivated or attenuated vaccines, face challenges in achieving a balance between immunogenicity and safety. To develop a green and efficient novel vaccine for ND and IBD, we developed a bivalent chimeric virus-like particle vaccine (ND-IBD cVLPs) displaying the ND virus (NDV) HN protein and the IBD virus (IBDV) VP2 protein based on the ND VLPs carrier platform and insect baculovirus expression system. This study aimed to evaluate the immunogenicity and protective efficacy of ND-IBD cVLPs in specific pathogen-free chickens. Chickens were immunized with 50 µg of purified ND-IBD cVLPs at 7 days old, boosted at 21 days old, and challenged at 42 days old. The results demonstrated that ND-IBD cVLPs stimulated highly effective hemagglutination inhibition antibody levels against NDV HN protein and enzyme-linked immunosorbent assay antibody levels against the IBDV VP2 protein. Furthermore, ND-IBD cVLPs provided complete protection against virulent NDV and IBDV challenges and mitigated pathological damage to the lung caused by NDV infection and the bursa of Fabricius caused by IBDV infection. These findings suggest that ND-IBD cVLPs hold promise as a safe and efficient novel vaccine candidate for the effective prevention of ND and IBD, extending the development of a foreign protein delivery platform of ND VLPs.

3D printing processes in precise drug delivery for personalized medicine.

With the advent of personalized medicine, the drug delivery system will be changed significantly. The development of personalized medicine needs the support of many technologies, among which three-dimensional printing (3DP) technology is a novel formulation-preparing process that creates 3D objects by depositing printing materials layer-by-layer based on the computer-aided design method. Compared with traditional pharmaceutical processes, 3DP produces complex drug combinations, personalized dosage, and flexible shape and structure of dosage forms (DFs) on demand. In the future, personalized 3DP drugs may supplement and even replace their traditional counterpart. We systematically introduce the applications of 3DP technologies in the pharmaceutical industry and summarize the virtues and shortcomings of each technique. The release behaviors and control mechanisms of the pharmaceutical DFs with desired structures are also analyzed. Finally, the benefits, challenges, and prospects of 3DP technology to the pharmaceutical industry are discussed.

Preparation of photothermal responsive, antibacterial hydrogel by using PVA-Alg and silver nanofibers as building blocks.

Introduction: Photothermal responsive, antimicrobial hydrogels are very attractive and have great potential in the field of tissue engineering. The defective wound environment and metabolic abnormalities in diabetic skin would lead to bacterial infections. Therefore, multifunctional composites with antimicrobial properties are urgently needed to improve the current therapeutic outcomes of diabetic wounds. We prepared an injectable hydrogel loaded with silver nanofibers for efficient and sustained bactericidal activity. Methods: To construct this hydrogel with good antimicrobial activity, homogeneous silver nanofibers were first prepared by solvothermal method and then dispersed in PVA-lg solution. After homogeneous mixing and gelation, injectable hydrogels (Ag@H) wrapped with silver nanofibers were obtained. Results: By virtue of Ag nanofibers, Ag@H exhibited good photothermal conversion efficiency and good antibacterial activity against drug-resistant bacteria, while the in vivo antibacterial also showed excellent performance. The results of antibacterial experiments showed that Ag@H had significant bactericidal effects on MRSA and E. coli with 88.4% and 90.3% inhibition rates, respectively. Discussion: The above results indicate that Ag@H with photothermal reactivity and antibacterial activity is very promising for biomedical applications, such as wound healing and tissue engineering.

Quantifying knowledge from the perspective of information structurization.

Scientific literature, as the major medium that carries knowledge between scientists, exhibits explosive growth in the last century. Despite the frequent use of many tangible measures, to quantify the influence of literature from different perspectives, it remains unclear how knowledge is embodied and measured among tremendous scientific productivity, as knowledge underlying scientific literature is abstract and difficult to concretize. In this regard, there has laid a vacancy in the theoretical embodiment of knowledge for their evaluation and excavation. Here, for the first time, we quantify the knowledge from the perspective of information structurization and define a new measure of knowledge quantification index (KQI) that leverages the extent of disorder difference caused by hierarchical structure in the citation network to represent knowledge production in the literature. Built upon 214 million articles, published from 1800 to 2021, KQI is demonstrated for mining influential classics and laureates that are omitted by traditional metrics, thanks to in-depth utilization of structure. Due to the additivity of entropy and the interconnectivity of the network, KQI assembles numerous scientific impact metrics into one and gains interpretability and resistance to manipulation. In addition, KQI explores a new perspective regarding knowledge measurement through entropy and structure, utilizing structure rather than semantics to avoid ambiguity and attain applicability.

Transcriptome-wide N6-methyladenosine modification profiling of mRNAs during infection of Newcastle disease virus in chicken macrophages.

N6-methyladenosine (m6A) modification, the most prevalent post-transcriptional modification of eukaryotic mRNAs, is reported to play a crucial role in viral infection. However, the role of m6A modification during Newcastle disease virus (NDV) infection has remained unclear. In this study, we performed MeRIP-seq to investigate the transcriptome-wide m6A methylome and m6A-modified genes in NDV-infected chicken macrophages. A total of 9496 altered peaks were identified, of which 7015 peaks were significantly upregulated across 3320 genes, and 2481 peaks were significantly down-regulated across 1264 genes. Combined analysis of m6A peaks and mRNA expression showed that 1234 mRNAs had significantly altered levels of methylation and expression after NDV infection, and m6A modification tended to have a negative relationship with mRNA expression, suggesting that m6A modification may regulate the process of NDV infection by regulating gene expression, particularly of the genes important in the innate immune response. To the best of our knowledge, this is the first comprehensive characterization of m6A patterns in chicken macrophage mRNA after NDV infection, providing a valuable basis for further exploring the role of m6A modification mechanisms during the course of NDV infection.