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Hong-Jin Wang,1,* Yan-Ping Feng,1,* Xiao-Xia Tian,2 Xiao-Han Wu,1 Li-Zhuang Hao,2 Yi Li,1 Shi-Juan Mei3 1Department of Burns and Plastic Surgery, Affiliated Hospital of Qinghai University, Xining, Qinghai, 810012, People’s Republic of China; 2Qinghai University, Academy of Animal Science and Veterinary Medicine, Key Laboratory of Plateau Grazing Animal Nutrition and Feed Science of Qinghai Province, Xining, Qinghai, 810016, People’s Republic of China; 3Department of Oncology, affiliated Hospital of Qinghai University, Xining, Qinghai, 810010, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi Li, Department of Burns and Plastic Surgery, Affiliated Hospital of Qinghai University, No. 29 Tongren Road, Xining, Qinghai province, 810010, People’s Republic of China, Tel +86-13709760887, Email liyily5t@126.com Shi-Juan Mei, Department of Oncology, Affiliated Hospital of Qinghai University, No. 29 Tongren Road, Xining, Qinghai province, 810010, People’s Republic of China, Tel +86-15009715352, Email meishijuanmsj8g@126.comObjective: Treatment of burn wound healing involves infection, nutrition, psychology and rehabilitation, and proper nutritional support can promote wound healing, enhance immune function and reduce the incidence of complications. This study aimed to investigate the effects of feed containing yak meat on scalded rats’ body condition and wound healing.Methods: Adopting a two-factor factorial design, the growth performance, food intake, body weight, and Lee’s index of rats were measured. The wound conditions of scalded rats with different feeds (basic, basic + yak meat, and basic + yellow beef) were observed at different periods, and their wounds’ hematoxylin and eosin (H&E) staining states were detected. The proliferating cell nuclear antigen (PCNA)-positive cells and apoptosis were analyzed to evaluate the effects of feed on the wound healing of scalded rats.Results: The feed intake was the highest in the yellow beef feed group and the lowest in the yak meat feed group. The body weight was the highest in the yak meat feed group and the lowest in the yellow beef feed group. Furthermore, 45 days after scalding, the obesity index in the yak beef feed group was the closest to that of the rats before scalding. The wound recovery of the rats in the yak meat feed group was the best at 30 days, and the H&E staining results also proved that the recovery effect of the scalded rats in the yak meat feed group was better than other two groups. According to the results of PCNA and apoptosis, the yak meat feed group had lower positive cell rate and faster wound healing.Conclusion: The rats in the yak meat feed group recovered better than those in the other groups, and the yak beef feed had the best effect on the wound healing of the scalded rats.Keywords: scalded rats, yak meat feed, yellow beef feed, basic feed, wound healing

Ying Yang,1 Ning Wang,2 XinXin Tian,1 XiaoLi Wang,1 Jing Yang,1 XiGang Leng,1 HaiLing Zhang1 1Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomaterials, Tianjin, People’s Republic of China; 2Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: HaiLing Zhang, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomaterials, Tianjin, People’s Republic of China, Tel +86 22 8789 1191, Fax +86 22 8789 0153, Email zhanghl@bme.pumc.edu.cnBackground: Tumor immunotherapy, a novel type of therapeutic treatment, has a wide range of applications with potentially prolonged benefits. However, current immunotherapy has a low overall response rate in treating a variety of tumors. Combination of immunotherapy with other therapies can improve the therapeutic response rates. The purpose of this work was to explore the potential of anti-angiogenic treatment in combination with tumor cell lysate loaded polydopamine nanoparticle vaccine as a therapeutic strategy for colon tumor.Methods: We grafted tumor cell lysate onto polydopamine nanoparticles as nano-vaccine (TCLN) and fabricated alginate hydrogel loaded with Endostar (EH), then detected characteristics of EH and TCLN. We also estimated the cytotoxicity of EH/TCLN in vitro. In the tumor-bearing mouse model, we evaluated the antitumor effect of EH/TCLN treatment, and developed the animal survival study. After performing the EH/TCLN treatment, we also analyzed T cells and DCs using flow cytometry, and determined T cell responses and tumor microenvironmental cytokines. At last, we assessed the effect of the EH/TCLN treatment on anti-angiogenesis further.Results: When applied in combination with TCLN in MC-38 tumor-bearing mice, EH/TCLN significantly suppressed tumor growth with more than half of the mice showing tumor regression. In addition, EH/TCLN treatment resulted in noticeable changes in the tumor microenvironment. As compared with the control group, EH/TCLN treatment led to significantly reduced tumor angiogenesis and expression of tumor microenvironment-related cytokines (TMCs), increased proportion of CD8+ T cells in the spleen, lymph node and tumor, elevated activity of cytotoxic T lymphocytes (CTLs) and tumor cell apoptosis.Conclusion: The present study demonstrated that the EH/TCLN treatment effectively created a favorable immune microenvironment for the induction of antitumor immunity and improved antitumor immune responses.Graphical Abstract: Keywords: alginate, polydopamine, Endostar, colon tumor, angiogenesis, immunotherapy

Introduction: Heparin-binding protein is an inflammatory factor with predictive value for sepsis and participates in the inflammatory response through antibacterial effects, chemotaxis, and increased vascular permeability. The role of heparin-binding protein in sepsis has been progressively demonstrated, but few studies have been conducted in the context of polytrauma combined with bacterial infections. This study aims to investigate the predictive value of heparin-binding protein for bacterial infections in patients with severe polytrauma., Materials and Methods: This is a prospective single-center study. Patients with polytrauma in the emergency intensive care unit were selected for the study, and plasma heparin-binding protein concentrations and other laboratory parameters were measured within 48 hours of admission to the hospital. A two-sample comparison and univariate logistic regression analysis investigated the relationship between heparin-binding protein and bacterial infection in polytrauma patients. A multifactor logistic regression model was constructed, and the ROC curve was plotted., Results: Ninety-seven patients with polytrauma were included in the study, 43 with bacterial infection and 54 without infection. Heparin-binding protein was higher in the infected group than in the control group [(32.00±3.20) ng/mL vs. (18.52±1.33) ng/mL, P = 0.001]. Univariate logistic regression analysis shows that heparin-binding protein is related to bacterial infection (OR = 1.10, Z = 3.91, 95%CI:1.05~1.15, P = 0.001). Multivariate logistic regression equations showed that patients were 1.12 times more likely to have bacterial infections for each value of heparin-binding protein increase, holding neutrophils and Procalcitonin (PCT) constant. ROC analysis shows that heparin-binding protein combined with neutrophils and PCT has better predictive value for bacterial infection [AUC = 0.935, 95%CI:0.870~0.977]., Conclusions: Heparin-binding protein may predict bacterial infection in patients with severe polytrauma. Combining heparin-binding protein, PCT, and neutrophils may improve bacterial infection prediction., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Artemisiae Scoporiae Herba is derived from Artemisia scoparia or A. capillaris. The accurate identification of the herbs, particularly when dealing with bulk samples, is critical for ensuring the quality and efficacy of the medicinal product. This study aimed to establish a comprehensive molecular approach by combining multiple markers for the precise identification of Artemisiae Scoporiae Herba. The ITS2 from A. scoparia, A. capillaris, and other common Artemisia species were retrieved from GenBank. MEGA was used to build a phylogenetic tree with these sequences, and the effectiveness of ITS2 in species identification was assessed. The analysis revealed that while ITS2 could distinguish Artemisiae Scoporiae Herba from other closely related species of Artemisia, it was insufficient to differentiate between A. scoparia and A. capillaris. To address this limitation, the chloroplast genome of A. capillaris was assembled and compared with the published chloroplast genomes of A. scoparia and A. capillaris, on the basis of which a DNA mini-barcode was developed. The rpoA-rps11 region was selected as the target for the development of mini-barcode due to its potential for distinguishing between these two species. Specific primers were designed to differentiate A. scoparia from A. capillaris. The ITS2 sequences and the newly developed mini-barcode were used together for Sanger sequencing to identify individual samples of Artemisiae Scoporiae Herba, while DNA metabarcoding was employed for the identification of bulk samples. The identification results of representative individual samples and bulk samples from different regions consistently confirmed A. capillaris. This study established a method that combined ITS2 and mini-barcode to identify bulk samples of Artemisiae Scoporiae Herba from different regions. This approach overcomes the limitations of morphological and chemical methods, enhancing species identification accuracy and supporting a stable supply of medicinal materials.

Myopia, a prevalent refractive error, primarily affects children and adolescents, characterized by excessive axial elongation causing distant objects to focus in front of the retina. This review explores the intricate mechanisms beyond intraocular factors, emphasizing the significant role of central factors in myopia development and progression. Intraocular mechanisms involving the retina, RPE/choroid, and sclera are well documented, with these structures playing crucial roles in eye growth regulation. Central factors, including brain structure and function alterations, are increasingly recognized, supported by advanced imaging techniques such as fMRI and rs-fMRI. Clinical findings highlight changes in brain activity and connectivity in high myopia (HM), suggesting neural plasticity or compensatory mechanisms. Animal studies further elucidate central mechanisms, indicating the involvement of specific brain nuclei like the visual cortex and suprachiasmatic nucleus. Understanding these complex interactions between intraocular and central mechanisms is crucial for developing novel therapeutic strategies to inhibit myopia progression and prevent associated complications. This review aims to provide a comprehensive analysis of current research, contributing to a deeper understanding of central factors of myopia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tian, Tian, Yang and Wu.)

Interferon-induced transmembrane 3 (IFITM3) is a membrane-associated protein that exhibits antiviral activities against a wide range of viruses through interactions with other cellular and viral proteins. However, knowledge of the mechanisms of IFITM3 in Porcine deltacoronavirus (PDCoV) infection has been lacking. In this study, we demonstrate that IFN-α treatment induces the upregulation of IFITM3 activity and thus attenuates PDCoV infection. PDCoV replication is inhibited in a dose-dependent manner by IFITM3 overexpression. To clarify the novel roles of IFITM3 during PDCoV infection, proteins that interact with IFITM3 were screened by TAP/MS in an ST cell line stably expressing IFITM3 via a lentivirus. We identified known and novel candidate IFITM3-binding proteins and analyzed the protein complexes using GO annotation, KEGG pathway analysis, and protein interaction network analysis. A total of 362 cellular proteins associate with IFITM3 during the first 24 h post-infection. Of these proteins, the relationship between IFITM3 and Rab9a was evaluated by immunofluorescence colocalization analysis using confocal microscopy. IFITM3 partially colocalized with Rab9a and Rab9a exhibited enhanced colocalization following PDCoV infection. We also demonstrated that IFITM3 interacts specifically with Rab9a. Our results considerably expand the protein networks of IFITM3, suggesting that IFITM3 participates in multiple cellular processes during PDCoV infection., 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: The expression patterns and prognostic value of Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) family genes in breast cancer remain to be elucidated., Methods: The expression levels, prognostic value, and biological function of PLODs were determined using Oncomine, cBioPortal, GEPIA, Timer, UALCAN, PrognoScan, GeneMANIA, Metascape, and breast cancer tissue microarrays., Results: The expressions of PLOD1 and PLOD3 were upregulated in breast cancer tissues, indicating worse clinical stages. High expression levels of PLOD family genes were associated with worse disease-free survival and distant metastasis-free survival, while high expression levels of PLOD1 and PLOD3 were related to worse overall survival in all breast cancer patients. The levels of PLOD family genes were all significantly higher in the age ≤51 y group, HR-negative patients, and triple negative breast cancer (TNBC) patients. They are associated with tumor-infiltrating immune cells (TIICs), including CD4+ T cells, CD8+ T cells, B cells, macrophages, neutrophils, and dendritic cells. According to co-expression gene analysis and functional enrichment, they are associated with protein hydroxylation, collagen biosynthesis and modifying enzymes, collagen metabolism, RNA splicing, extracellular matrix organization, VEGFA-VEGFR2 signaling pathway, and skeletal system development. Immunohistochemistry showed that the expressions of all PLOD family genes were significantly elevated in breast cancer tissues. PLOD1 expression was positively correlated with ER, TNBC status, and tumor grade. PLOD2 expression was positively connected with Ki-67 status. PLOD3 expression was positively related with age and tumor grade., Conclusions: PLOD family genes are novel potential prognostic biomarkers for breast cancer, and targeting PLOD inhibitors might be an effective strategy for breast cancer therapy.

To evaluate the effects of varying proportions of yak meat in feed on the growth of rats and provide a theoretical basis for selecting the optimal feed proportion suitable for rats. This study was designed as a one-variable experiment. Fifty male rats were divided into five groups. The ratios of yak meat to basal feed of rats in four dietary treatment groups were 2:8, 4:6, 6:4, and 8:2, respectively, while those in the control group were only provided a basal diet. In the feeding experiment, the body weights of the rats were recorded on Day 0 and subsequently in the first, second, third, and fourth weeks, along with quantities of feed intake. The body and tail lengths, as well as the waist circumference of the rats, were measured, and blood samples were collected in the fourth week for routine blood and biochemistry investigations. The rats in the 4:6 feed group had the best body condition. They had normal body and tail lengths, smaller waist circumferences, good posture, and were in better overall health than rats in the other groups. The results indicate that the 4:6 diet was optimal for enhancing rats' growth performance compared to the other diets., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2024 the author(s), published by De Gruyter.)

Objective: To investigate the clinicopathological characteristics of acidophil stem cell pituitary neuroendocrine tumors (PitNET)/adenoma. Methods: Five cases of acidophil stem cell PitNET/adenoma were diagnosed between May 2022 and July 2023 at the Second Hospital of Hebei Medical University, Shijiazhuang, China. The clinicopathological features of the tumor were analyzed by using histology, immunohistochemistry, and electron microscopy. The relevant literature was reviewed. Results: There were 1 male and 4 females, aged from 23 to 69 years. Patient 3 was 55 years old at the time of diagnosis and first surgery, and relapsed 5 years later. The patients' median age was 32 years. Patients 1 and 5 showed elevated blood prolactin, with various degrees of hormonal symptoms except Patient 3, who showed only tumor compression symptoms. Imaging studies showed that all cases involved the sellar floor. The tumors of Patients 1, 2 and 5 were closely related to the cavernous sinus segment of the internal carotid artery. The tumors exhibited a diffuse growth pattern with chromophobic to slightly acidophilic cytoplasm. A few of tumor cells showed chromophobic cytoplasm. The nucleoli were conspicuous. Intranuclear inclusion bodies and variably-sized clear vacuoles were observed occasionally. Under electron microscope, marked mitochondrial abnormalities were observed, including increased mitochondria number, expanded hypertrophy, and absence of mitochondrial ridge fracture. Some mitochondrial matrices were dense, while some were vacuolated. Conclusions: Acidophil stem cell PitNET/adenoma is a rare type of pituitary adenomas/PitNETs. It often has a more clinically aggressive manner with immature cells, diffuse expression of PIT1, prolactin, and varying degrees of growth hormone expression. Because of the obvious diversity of their clinical hormone status and hormone immune expression, the diagnosis of this type tumor is still a challenge.

Porcine reproductive and respiratory syndrome virus (PRRSV) is an important pathogen that causes huge economic losses to the global pig industry. Nonstructural protein 7α (NSP7α) of PRRSV is highly conserved among different lineages of PRRSV and could be a potential target for the development of detection methods. In this study, NSP7α was expressed in prokaryote (Escherichia coli) and purified. An NSP7α-ab-ELISA detection method was established, the NSP7α-ab-ELISA has 93.1 % coincidence rate with IDEXX PRRS X3 ab test kit. NSP7α antibody was detected in pig serum by ELISA 14 days following PRRSV infection. Three monoclonal antibodies (4H9, 3F2, and C10) against NSP7α prepared by a hybridoma technique were used for epitope mapping by indirect immunofluorescence. The 4H9, 3F2, and C10 antibodies all recognized the C-terminal 72-149 amino acid region of NSP7α. 4H9 reacted with amino acids 135-143, but 3F2 and C10 did not react with any truncated polypeptide. In addition, by using the monoclonal antibodies, NSP7α was localized solely in the cytoplasm, while the N protein was distributed in the cytoplasm and nucleus. The collective findings of the antigenicity and epitope of NSP7α will be helpful for understanding the antigenicity of NSP7α and developing PRRSV diagnostic methods., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tongqing An reports financial support was provided by the Heilongjiang Provincial Natural Science Foundation of China. Tongqing An reports financial support was provided by Heilongjiang Key Research and Development Program. Tongqing An reports financial support was provided by the National Natural Science Foundation of China., (Copyright © 2024 Elsevier B.V. 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.)

Spontaneous subarachnoid hemorrhage (SAH) is an acute neurologic emergency with poor outcomes, and mitochondrial dysfunction is known as one of the key pathological mechanisms underlying the SAH-induced early brain injury (EBI). 1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl} azetidin-3-ol maleate (T817MA) is a newly synthesized neurotrophic compound that has been demonstrated to exert protective effects against brain injury. Here, we investigated the effect of T817MA in neuronal injury following experimental SAH both in vitro and in vivo. Primary cultured cortical neurons were treated with oxyhemoglobin (OxyHb) to mimic SAH in vitro, and T817MA at concentrations higher than 0.1 μM reduced OxyHb-induced neuronal injury. T817MA treatment significantly inhibited lipid peroxidation, reduced neuronal apoptosis and attenuated mitochondrial fragmentation. The results of western blot showed that T817MA markedly reduced the expression of mitochondrial fission proteins, fission protein 1 (Fis-1) and dynamin-related GTPase-1 (Drp-1), but prolonged the expression of the postsynaptic protein activity-regulated cytoskeleton-associated protein (Arc). In addition, T817MA significantly increased the expression of sirtuin 1 (Sirt1), which was accompanied by preserved enzymatic of isocitrate dehydrogenase (IDH2) and superoxide dismutase (SOD). Knockdown of Sirt1 and Arc via small interfere RNA (siRNA) transfection partially prevented the T817MA-induced protection in cortical neurons. Furthermore, treatment with T817MA in vivo significantly reduced brain damage and preserved neurological function in rats. The decreased expression of Fis-1 and Drp-1, as well as the increased expression of Arc and Sirt1 were also observed in vivo. Taken together, these data indicate that the neuroprotective agent T817MA protects against SAH-induced brain injury via Sirt1- and Arc-mediated regulation of mitochondrial dynamics., (Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.)

This study explores new applications of black phosphorus quantum dots (BPQDs) by adding them to self-healing material systems for the first time. Self-healing polyurethane with an ultra-small amount of BPQDs has biomimetic intelligent responsiveness and achieves balance between its mechanical and self-healing properties. By adding 0.0001 wt% BPQDs to self-healing polyurethane, the fracture strength of the material increases from 3.0 to 12.3 MPa, and the elongation at break also increases from 750% to 860%. Meanwhile, the self-healing efficiency remains at 98%. The addition of BPQDs significantly improves the deformation recovery ability of the composite materials and transforms the surface of self-healing polyurethane from hydrophilic to hydrophobic, making it suitable for applications in fields such as electronic skin and flexible wearable devices. This study provides a simple and feasible strategy for endowing self-healing materials with biomimetic intelligent responsiveness using a small amount of BPQDs., (© 2023 Wiley-VCH GmbH.)

Background: The prognostic value of coronary artery calcium (CAC) combined with risk factor burdens in middle-aged and elderly patients with symptoms is unclear., Methods: A cohort study comprising 7432 middle-aged and elderly symptomatic patients (aged above 55 years) was conducted between December 2013 and September 2020. All patients had undergone coronary computed tomography angiography, and the Agatston score were used to measure CAC scores. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), which was defined as a composite outcome of nonfatal myocardial infarction, revascularization (percutaneous coronary intervention or coronary artery bypass graft), stroke, and cardiovascular death. Congestive heart failure, cardiogenic shock, malignant arrhythmia, and all-cause mortality were defined as the secondary outcomes., Results: There are 970 (13%) patients with CAC 0-10, 2331 (31%) patients with CAC 11-100, and 4131 (56%) patients with CAC ≥ 101. The proportion of patients aged 55-65 years, 65-75 years and ≥ 75 years was 40.7%, 38.1% and 21.2%, respectively. The total number of MACCEs over the 3.4 years follow-up period was 478. The percentage of CAC ≥ 101 was higher among the 75-year-old group than the 55-65-year-old group, increasing from 46.5% to 68.2%. With the increase in the CAC score, the proportion of patients aged ≥ 75 years increased from 12.9% to 25.8%, compared to those aged 55-65 years. The number of risk factors gradually increased as the CAC scores increased in the symptomatic patients aged over 55 years and the similar tendencies were observed among the different age subgroups. The proportion of non-obstructive coronary artery disease (CAD) was comparable between the three age groups (53.5% vs 51.9% vs 49.1%), but obstruction CAD increased with age. The incidence of MACCE in the group with CAC ≥ 101 and ≥ 4 risk factors was 1.71 times higher (95% confidence interval (CI) 1.01-2.92; p = 0.044) than the rate in the group with CAC ≥ 101 and 1 risk factor. In the CAC 0-10 group, the incidence of MACCE in patients aged ≥ 75 years was 12.65 times higher (95% CI: 6.74-23.75; p < 0.0001) than that in patients aged 55-65 years. By taking into account the combination of CAC score, age, and risk factor burden, the predictive power of MACCE can be increased (area under the curve (AUC) = 0.614)., Conclusions: In symptomatic patients aged 55 or above, a rise in age, CAC scores, and risk factor burden was linked to a considerable risk of future MACCE. In addition, combining CAC scores, age and risk factors can more accurately predict outcomes for middle-aged and elderly patients with symptoms., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 The Author(s). Published by IMR Press.)

Objective: The aim of this work was to evaluate the predictive value of FAR combined with CACS for MACCEs., Background: The fibrinogen-albumin-ratio (FAR), a novel biomarker of inflammation, is associated with the severity of coronary artery disease (CAD). Coronary calcification score (CACS) is associated with the severity of coronary stenosis and is closely related to the prognosis of CAD patients. What is the prognostic value of FAR in patients with chest pain, which has not been reported. This study aims to evaluate the relationship between CACS and FAR and their impact on prognosis in patients with suspected CAD., Methods: We used information from 12,904 individuals who had coronary computed tomography angiography (CTA) for chest pain and tracked down any significant adverse cardiac and cerebrovascular events (MACCEs). The following formula was used to calculate FAR: fibrinogen (g/L)/albumin (g/L). Patients were separated into groups with greater levels of FAR (FAR-H) and lower levels of FAR (FAR-L) in accordance with the ideal cut-off value of FAR for MACCEs prediction. In addition, patients were divided into three groups based on their CACS scores (CACS ≤ 100, 100 < CACS ≤ 400, and CACS > 400)., Results: 4946 patients [62(55-71) years, 64.4% male] were ultimately enrolled in the present study. During follow-up, a total of 234 cases (4.7%) of MACCEs were documented. Linear regression analysis results showed that CACS (R2 = 0.004, Standard β = 0.066, P < 0.001) was positively associated with FAR in patients with chest pain.Compared to ones with FAR-L, FAR-H had an increased risk for MACCEs (adjusted HR 1.371(1.053-1.786) P = 0.019). Multivariate Cox regression showed that age (adjusted HR 1.015 95% CI 1.001-1.028;p = 0.03), FAR (adjusted HR 1.355 95% CI 1.042-1.763;p = 0.023),FBG (adjusted HR 1.043 95% CI 1.006-1.083;p = 0.024) and CACS (adjusted HR 1.470 95% CI 1.250-1.727;p < 0.001) were the independent risk factors for MACCEs. The FAR and CACS significantly improved MACCEs risk stratification, contributing to substantial net reclassification improvement ( NRI 0.122, 95% CI 0.054-0.198, P < 0.001) and integrated discrimination improvement(IDI 0.011, 95% CI 0.006-0.017, P < 0.001)., Conclusion: FAR was an independent risk factor for MACCEs. The results showed that CACS was positively associated with FAR in patients with suspected CAD. A higher level of FAR and heavier coronary calcification burden was associated with worse outcomes among patients with suspected CAD. FAR and CACS improved the risk identification of patients with suspected CAD, leading to a significant reclassification of MACCEs., (© 2023. The Author(s).)

Objectives: The aim of this study was to examine the independent and joint associations of baseline coronary artery calcium score (CACS) and cystatin C (Cys-C) with the risk of major adverse cardiac and cerebrovascular events (MACCEs) and all-cause death in symptomatic populations., Methods: The study included 7140 patients with symptom of chest pain who underwent cardiac computerized tomography examinations to measure CACS. All of them had serum Cys-C results. Endpoints were set for MACCEs and all-cause death events., Results: A total of 7140 participants were followed for a median of 1106 days. A total of 305 patients had experienced MACCEs and 191 patients had experienced all-cause death. CACS ≥ 100 and Cys-C ≥ 0.995 mg/L were independently associated with an increased risk of MACCEs (adjusted hazard ratio [HR]: 1.46; 95% confidence interval [CI]: 1.15-1.85; p = .002 and adjusted HR: 1.57; 95% CI: 1.24-2.00; p < .001, respectively). Compared with CACS < 100 and Cys-C < 0.995 mg/L patients, CACS ≥ 100 and Cys-C ≥ 0.995 mg/L patients had the highest risk of MACCEs and all-cause death (adjusted HR: 2.33; 95% CI: 1.64-3.29; p < .001 and adjusted HR: 2.85; 95% CI: 1.79-4.55; p < .001, respectively). Even in patients with CACS < 100, Cys-C ≥ 0.995 mg/L was also associated with a higher risk of MACCEs and all-cause death than Cys-C < 0.995 mg/L (adjusted HR: 1.76; p = .003 and adjusted HR: 2.02; p = .007, respectively)., Conclusions: The combined stratification of CACS and Cys-C showed an incremental risk of MACCEs and all-cause death, reflecting complementary prognostic value. Our results support the combination of the two indicators for risk stratification and event prediction., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Consuming fish oils (FO) is linked to reduced risk of cardiovascular disease in certain populations. However, FO failed to exhibit therapeutic effects in some patients with cardiovascular disease. This study aimed to determine the possible reasons for the inconsistent effects of FO. AMP-activated protein kinase (AMPK) α2 is an important energy metabolic sensor, which was reported to involve in FO mediated regulation of lipid and glucose metabolism. In an in vivo study, FO administration significantly reduced the aortic lesions and inflammation in the Ldlr -/- mouse model of atherosclerosis, but not in Ldlr -/- /Prkaa2 -/- and Ldlr -/- /Prkaa2 -/-Sm22Cre mice. Mechanistically, inactivation of AMPKα2 increased the SUMOylation of the fatty acid receptor GPR120 to block FO-induced internalization and binding to β-arrestin. In contrast, activation of AMPKα2 can phosphorylate the C-MYC at Serine 67 to inhibit its trans-localization into the nuclei and transcription of SUMO-conjugating E2 enzyme UBC9 and SUMO2/3 in vascular smooth muscle cells (VSMCs), which result in GPR120 SUMOylation. In human arteries, AMPKα2 levels were inversely correlated with UBC9 expression. In a cohort of patients with atherosclerosis, FO concentrations did not correlate with atherosclerotic severity, however, in a subgroup analysis a negative correlation between FO concentrations and atherosclerotic severity was found in patients with higher AMPKα2 levels. These data indicate that AMPKα2 is required for the anti-inflammatory and anti-atherosclerotic effects of FO., (© 2022. The Author(s).)

A 2D Co-MOF, {[Co 2 (L 2- ) 2 (bipy)](DMA)·2H 2 O} n (Co-1, H 2 L = 2,5-thienedioic acid; bipy = 2,2'-bipyridine; DMA = N , N '-dimethyl acetamide), was synthesized by hydrothermal method. Co-1 has excellent air stability. When modifying the surface of a glassy carbon electrode (GCE) with Co-1, the obtained electrochemical senor Co-1/GCE shows excellent sensitivity towards 1,3-dinitrobenzene ( m -DNB) and 2,4-dinitroaniline (2,4-DNA), although the electrochemical conductivity of Co-1 is not that good. The detection limits were as low as 0.0286 μM and 0.161 μM, respectively. DFT studies showed that the main interaction between Co-1 and the guest molecules is via hydrogen bonding, formed by the -NO 2 group and the coordinated H 2 O molecule from the Co-1 skeleton. Furthermore, the characteristic signals of both m -DNB and 2,3-DNA can still be observed in a mimicked industrial waste-water system containing 17 kinds of organic interferents, indicating high selectivity of the Co-1/GCE sensor.

Background Restenosis is one of the main bottlenecks in restricting the further development of cardiovascular interventional therapy. New signaling molecules involved in the progress have continuously been discovered; however, the specific molecular mechanisms remain unclear. MTMR14 (myotubularin-related protein 14) is a novel phosphoinositide phosphatase that has a variety of biological functions and is involved in diverse biological processes. However, the role of MTMR14 in vascular biology remains unclear. Herein, we addressed the role of MTMR14 in neointima formation and vascular smooth muscle cell (VSMC) proliferation after vessel injury. Methods and Results Vessel injury models were established using SMC-specific conditional MTMR14-knockout and -transgenic mice. Neointima formation was assessed by histopathological methods, and VSMC proliferation and migration were assessed using fluorescence ubiquitination-based cell cycle indicator, transwell, and scratch wound assay. Neointima formation and the expression of MTMR14 was increased after injury. MTMR14 deficiency accelerated neointima formation and promoted VSMC proliferation after injury, whereas MTMR14 overexpression remarkably attenuated this process. Mechanistically, we demonstrated that MTMR14 suppressed the activation of PLK1 (polo-like kinase 1) by interacting with it, which further leads to the inhibition of the activation of MEK/ERK/AKT (mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase/protein kinase B), thereby inhibiting the proliferation of VSMC from the medial to the intima and thus preventing neointima formation. Conclusions MTMR14 prevents neointima formation and VSMC proliferation by inhibiting PLK1. Our findings reveal that MTMR14 serves as an inhibitor of VSMC proliferation and establish a link between MTMR14 and PLK1 in regulating VSMC proliferation. MTMR14 may become a novel potential therapeutic target in the treatment of restenosis.

Porcine reproductive and respiratory syndrome (PRRS), caused by the PRRS virus (PRRSV), is a significant threat to the global pig industry. In this study, a novel recombinant PRRSV, SD043, was isolated from a pig farm experiencing disease in 2019. Phylogenetic analysis revealed that SD043 belonged to lineage 1 of PRRSV-2 while recombination analyses revealed that it is a recombinant virus from lineage 1 and lineage 8 strains. Based on further analysis, SD043 underwent recombination twice. Pathogenicity studies revealed that SD043 causes mild clinical symptoms, thymus atrophy, and severe histopathological lesions in the lungs. Notably, virus shedding in SD043-infected piglets was detectable at 10 days post-inoculation with a high viral load in the respiratory or digestive tract, indicating that the recombinant PRRSV appears to shed higher numbers of virus. Furthermore, genomic surveillance based on all available PRRSVs circulating in Shandong province revealed an increasing increase in recombinant PRRSV since 2015, with the recombinant pattern (between lineages 1 and 8) being the same as that of SD043. These findings enable a better understanding of the process of twice recombination and virus shedding of recombinant PRRSV and can strengthen the prevention and control of the PRRSV epidemic., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Platelet-related parameters and HDL-C have been regarded as reliable and alternative markers of coronary heart disease (CHD) and the independent predictors of cardiovascular outcomes. PDW is a simple platelet index, which increases during platelet activation. Whether the PDW/HDL-C ratio predicts major adverse cardiovascular and cerebrovascular events (MACCEs) in patients who complained of chest pain and confirmed coronary artery calcification remains to be investigated. This study aimed to investigate the prognostic value of the PDW/HDL-C ratio in patients with chest pain symptoms and coronary artery calcification., Methods: A total of 5,647 patients with chest pain who underwent coronary computer tomography angiography (CTA) were enrolled in this study. Patients were divided into two groups according to their PDW/HDL-C ratio or whether the MACCE occurs. The primary outcomes were new-onset MACCEs, defined as the composite of all-cause death, non-fatal MI, non-fatal stroke, revascularization, malignant arrhythmia, and severe heart failure., Results: All patients had varying degrees of coronary calcification, with a mean CACS of 97.60 (22.60, 942.75), and the level of CACS in the MACCEs group was significantly higher than that in non-MACCE (P<0.001). During the 89-month follow-up, 304 (5.38%) MACCEs were recorded. The incidence of MACCEs was significantly higher in patients with the PDW/HDL-C ratio > 13.33. The K-M survival curves showed that patients in the high PDW/HDL-C ratio group had significantly lower survival rates than patients in the low PDW/HDL-C ratio group (log-rank test: P < 0.001). Multivariate Cox hazard regression analysis reveals that the PDW/HDL ratio was an independent predictor of MACCEs (HR: 1.604, 95% CI: 1.263-2.035; P < 0.001). Cox regression analysis showed that participants with a lower PDW/HDL-C ratio had a higher risk of MACCEs than those in the higher ratio group. The incidence of MACCEs was also more common in the PDW/HDL-C ratio > 13.33 group among different severities of coronary artery calcification. Furthermore, adding the PDW/HDL-C ratio to the traditional prognostic model for MACCEs improved C-statistic ( P < 0.001), the NRI value (11.3% improvement, 95% CI: 0.018-0.196, P = 0.01), and the IDI value (0.7% improvement, 95% CI: 0.003-0.010, P < 0.001)., Conclusion: The higher PDW/HDL-C ratio was independently associated with the increasing risk of MACCEs in patients with chest pain symptoms and coronary artery calcification. In patients with moderate calcification, mild coronary artery stenosis, and CAD verified by CTA, the incidence of MACCEs increased significantly in the PDW/HDL-C ratio > 13.33 group. Adding the PDW/HDL-C ratio to the traditional model provided had an incremental prognostic value for MACCEs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qiu, Luo, Luo, Tian, Zeng, Zhang, Li and Yang.)

Our previous works have indicated that extracellular ATP is an important prometastasis factor. However, the molecular mechanism involved needs to be further studied. We demonstrated that extracellular ATP treatment could upregulate the expression of connective tissue growth factor (CTGF) in both triple-negative breast cancer (TNBC) cells and endothelial cells (ECs). Extracellular ATP stimulated the migration of TNBC cells and ECs, and angiogenesis of ECs via the P2Y2--YAP-CTGF axis. Furthermore, we demonstrated that adenosine triphosphate (ATP) stimulated TNBC cell adhesion to ECs and transmigration through the EC layer via CTGF by upregulation of integrin β1 on TNBC cells and VCAM-1 on ECs. Both apyrase (ATP-diphosphohydrolase) and CTGF shRNA treatments could inhibit the metastasis of inoculated tumors to lung and liver in a mouse model, and these treated tumors had fewer blood vessels. Collectively, our data indicated that extracellular ATP promotes tumor angiogenesis and the interactions between TNBC cells and ECs through upregulation of CTGF, thereby stimulating TNBC metastasis. The pleiotropic effects of ATP in angiogenesis and cell adhesion suggest that extracellular ATP or CTGF could be an effective target for TNBC therapy., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

A safe, biocompatible, and stimuli-responsive cucurbit[7]uril-mediated supramolecular bactericidal nanoparticle was fabricated by encapsulating a highly bioactive carbazole-decorated imidazolium salt ( A 1 , EC 50 = 0.647 μg/mL against phytopathogen Xanthomonas oryzae pv oryzae ) into the host cucurbit[7]uril (CB[7]), thereby leading to self-assembled topographies from microsheets ( A 1 ) to nanospheroidal architectures ( A 1 @CB[7]). The assembly behaviors were elucidated by acquired single-crystal structures, 1 H NMR, ITC, and X-ray powder diffraction experiments. Complex A 1 @CB[7] displayed lower phytotoxicity and could efficiently switch on its potent antibacterial ability via introducing a simple competitor 1-adamantanamine hydrochloride (AD). In vivo antibacterial trials against rice bacterial blight revealed that A 1 @CB[7] could relieve the disease symptoms after being triggered by AD and provide a workable control efficiency of 42.6% at 100 μg/mL, which was superior to bismerthiazol (33.4%). These materials can provide a viable platform for fabricating diverse stimuli-responsive supramolecular bactericides for managing bacterial infections with improved safety.

Introducing 2,3-dimethyl-1 H -imidazol-3-ium iodide (Dmim) as a monodentate ligand during the preparation of ZIF-8 yields ZIF-8 + (50) and ZIF-8 + (38) with cationic 'missing linker' defects. ZIF-8 + (38) adsorbs 125 I 2 and the resulting radioactive host-guest complex exhibits in vitro cytotoxicity comparable to that of Na 125 I against colon cancer cell line CT26.

Most genome-wide association study (GWAS)-identified breast cancer-associated causal variants remain uncharacterized. To provide a framework of understanding GWAS-identified variants to function, we performed a comprehensive study of noncoding regulatory variants at the NTN4 locus (12q22) and NTN4 gene in breast cancer etiology. We find that rs11836367 is the more likely causal variant, disrupting enhancer activity in both enhancer reporter assays and endogenous genome editing experiments. The protective T allele of rs11837367 increases the binding of GATA3 to the distal enhancer and up-regulates NTN4 expression. In addition, we demonstrate that loss of NTN4 gene in mice leads to tumor earlier onset, progression, and metastasis. We discover that NTN4 , as a tumor suppressor, can attenuate the Wnt signaling pathway by directly binding to Wnt ligands. Our findings bridge the gaps among breast cancer-associated single-nucleotide polymorphisms, transcriptional regulation of NTN4 , and breast cancer biology, which provides previously unidentified insights into breast cancer prediction and prevention.

Porcine reproductive and respiratory syndrome (PRRS) is a widespread disease with great economic importance in the pig industry. Although vaccines against the PRRS virus (PRRSV) have been employed for more than 20 years, differentiating infected from vaccinated animals remains challenging. In this study, all 907 non-structural protein 2 (NSP2) full-length sequences of PRRSV-2 available from GenBank were aligned. Two peptides, at positions 562-627 (m1B) and 749-813 (m2B) of NSP2, were selected, and their potential for use in differential diagnosis was assessed. Both m1B and m2B were recognized by PRRSV-positive pig serum in peptide-coated enzyme-linked immunosorbent assays. Further epitope identification yielded five overlapping short peptides for the immunodominant regions of m1B and m2B. Using the infectious clone of PRRSV HuN4-F112 as a template, the deletion mutants, rHuN4-F112-m1B, rHuN4-F112-m2B, and rHuN4-F112-C5-m1B-m2B, were generated and successfully rescued in Marc-145 cells. Growth kinetics revealed that the deletion of m1B and m2B did not significantly affect virus replication. Hence, m1B and m2B show potential as molecular markers for developing a PRRSV vaccine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Cui, Huang, Hu, Tian, Wang, Yang, Wang, Tian, Cai and An.)

Objective: To explore the clinical characterist ics and risk factors of hemorrhage complicated by hemoperfusion therapy in patients with acute poisoning. Methods: In January 2021, the clinical data of 196 patients with acute poisoning who received hemoperfusion therapy in the Second Affiliated Hospital of Air Force Military Medical University from January 2018 to December 2020 were analyzed, and the patients were divided into bleeding group and non-bleeding group according to whether the patients were complicated with bleeding. Multivariate logistic regression was used to analyze the independent risk factors for hemorrhage in patients treated with hemoperfusion. Results: A total of 21 patients in the bleeding group and 175 patients in the non-bleeding group were included. There was no significant difference in general data such as gender, age, and body mass index between the two groups ( P >0.05) . Organophosphorus pesticides (χ(2)= 4.56, P =0.030) , HA230 perfusion device (χ(2)=4.12, P =0.042) , platelet count ( t =-2.33, P =0.009) and activated partial thromboplastin time ( t =14.53, P <0.001) at 2 h of perfusion were the influencing factors of hemorrhage in patients with acute poisoning treated with hemoperfusion. Among them, organophosphorus pesticides, 2 h perfusion activated partial thromboplastin time ≥35 s and other factors were independent risk factors forcomplicated bleeding ( P <0.05) . Conclusion: Patients with acute poisoning, especially organophosphorus pesticide poisoning, are at greater risk of bleeding during hemoperfusion therapy. Monitoring of changes in activated partial thromboplastin time should be strengthened and the dose of anticoagulants should be adjusted in time to reduce the risk of bleeding.

We have previously demonstrated that extracellular adenosine 5'-triphosphate (ATP) promotes breast cancer cell chemoresistance. However, the underlying mechanism remains unclear. Using a cDNA microarray, we demonstrated that extracellular ATP can stimulate hypoxia-inducible factor (HIF) signaling. In this study, we report that hypoxia-inducible factor 1α (HIF-1α) was upregulated after ATP treatment and mediated the ATP-driven chemoresistance process. We aimed to investigate the mechanisms and identify potential clinically relevant targets that are involved. Using mass spectrometry, we found that aldolase A (ALDOA) interacts with HIF-1α and increases HIF-1α expression. We then demonstrated that STAT3-ALDOA mediates ATP-HIF-1α signaling and upregulates the HIF-1 target genes adrenomedullin (ADM) and phosphoinositide-dependent kinase-1 (PDK1). Moreover, we show that PI3K/AKT acts upstream of HIF-1α in ATP signaling and contributes to chemoresistance in breast cancer cells. In addition, HIF-1α-knockdown or treatment with direct HIF inhibitors combined with the ATP hydrolase apyrase in MDA-MB-231 cells induced enhanced drug sensitivity in nude BALB/c mice. We then used in vitro spheroid formation assays to demonstrate the significance of ATP-HIF-1α in mediating chemoresistance. Furthermore, considering that indirect HIF inhibitors are effective in clinical cancer therapy, we treated tumor-bearing BALB/c mice with STAT3 and PI3K/AKT inhibitors and found that the dual-targeting strategy sensitized breast cancer to cisplatin. Finally, using breast cancer tissue microarrays, we found that ATP-HIF-1α signaling is associated with cancer progression, poor prognosis, and resistance to chemotherapy. Taken together, we suggest that HIF-1α signaling is vital in ATP-driven chemoresistance and may serve as a potential target for breast cancer therapies., (© 2022. The Author(s).)

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating infectious diseases in the global swine industry. A rapid and sensitive on-site detection method for PRRS virus (PRRSV) is critically important for diagnosing PRRS. In this study, we established a method that combines reverse transcription recombinase polymerase amplification (RT-RPA) with a lateral flow dipstick (LFD) for detecting North American PRRSV (PRRSV-2). The primers and probe were designed based on the conserved region of all complete PRRSV-2 genomic sequences available in China (n = 512) from 1996 to 2020. The detection limit of the assay was 5.6 × 10 -1 median tissue culture infection dose (TCID 50 ) per reaction within 30 min at 42 °C, which was more sensitive than that of reverse transcription polymerase chain reaction (RT-PCR) (5.6 TCID 50 per reaction). The assay was highly specific for the epidemic lineages of PRRSV-2 in China and did not cross-react with pseudorabies virus, porcine circovirus 2, classical swine fever virus, or porcine epidemic diarrhea virus. The assay performance was evaluated by testing 179 samples and comparing the results with those of quantitative RT-PCR (RT-qPCR). The results showed that the detection coincidence rate of RT-RPA and RT-qPCR was 100% when the cycle threshold values of RT-qPCR were < 32. The assay provides a new alternative for simple and reliable detection of PRRSV-2 and has great potential for application in the field., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Methylphenidate (MPH) is the first-line drug for the treatment of children with attention-deficit hyperactivity disorder (ADHD); however, individual curative effects of MPH vary. Many studies have demonstrated that synaptosomal-associated protein 25 ( SNAP-25 ) gene Mnl I polymorphisms may be related to the efficacy of MPH. However, the association between SNAP-25Mnl I polymorphisms and changes in brain hemodynamic responses after MPH treatment is still unclear. This study used functional near-infrared spectroscopy (fNIRS) to preliminarily investigate the interaction of MPH treatment-related prefrontal inhibitory functional changes with the genotype status of the SNAP-25 gene in children with ADHD. In total, 38 children with ADHD aged 6.76-12.08 years were enrolled in this study and divided into the following two groups based on SNAP-25 gene Mnl I polymorphisms: T/T genotype group (wild-type group, 27 children) and G allele carrier group (mutation group, 11 children). The averaged oxygenated hemoglobin concentration changes [Δavg oxy-Hb] and deoxyhemoglobin concentration changes [Δavg deoxy-Hb] in the frontal cortex before MPH treatment and after 1.5 h (post-MPH 1.5h ) and 4 weeks (post-MPH 4w ) of MPH treatments were monitored using fNIRS during the go/no-go task. SNAP-IV scores were evaluated both pre-MPH and post-MPH 4w treatments. In the T/T genotype group, [Δavg oxy-Hb] in the dorsolateral prefrontal cortex was significantly higher after 4 weeks of MPH (post-MPH 4W ) treatment than pre-treatment; however, in the G allele group, no significant differences in [Δavg oxy-Hb] were observed between pre- and post-treatments. In the go/no-go task, the accuracy was significantly increased post-MPH 4w treatment in the T/T genotype group, while no significant differences were observed in response time and accuracy of the "go" sand no-go task in the G allele group for pre-MPH, post-MPH 1.5h , and post-MPH 4w treatments. The T/T genotype group exhibited a significant decrease in SNAP-IV scores after MPH treatment, while the G allele group showed no significant difference. In conclusion, fNIRS data combined with SNAP-25 Mnl I polymorphism analysis may be a useful biomarker for evaluating the effects of MPH in children with ADHD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Yan, Wu, Tian and Zhang.)

Neutral three-dimensional Eu 3+ - and Tb 3+ -based metal-organic frameworks (MOFs) with 4-fold interpenetration can be produced by seeding with anionic Cd 2+ -based MOF crystallites of identical connectivity. In the absence of these crystallites, two-dimensional networks are formed.

SARS-CoV-2, the causative agent of COVID-19 1 , features a receptor-binding domain (RBD) for binding to the host cell ACE2 protein 1-6 . Neutralizing antibodies that block RBD-ACE2 interaction are candidates for the development of targeted therapeutics 7-17 . Llama-derived single-domain antibodies (nanobodies, ~15 kDa) offer advantages in bioavailability, amenability, and production and storage owing to their small sizes and high stability. Here, we report the rapid selection of 99 synthetic nanobodies (sybodies) against RBD by in vitro selection using three libraries. The best sybody, MR3 binds to RBD with high affinity (K D  = 1.0 nM) and displays high neutralization activity against SARS-CoV-2 pseudoviruses (IC 50  = 0.42 μg mL -1 ). Structural, biochemical, and biological characterization suggests a common neutralizing mechanism, in which the RBD-ACE2 interaction is competitively inhibited by sybodies. Various forms of sybodies with improved potency have been generated by structure-based design, biparatopic construction, and divalent engineering. Two divalent forms of MR3 protect hamsters from clinical signs after live virus challenge and a single dose of the Fc-fusion construct of MR3 reduces viral RNA load by 6 Log 10 . Our results pave the way for the development of therapeutic nanobodies against COVID-19 and present a strategy for rapid development of targeted medical interventions during an outbreak., (© 2021. The Author(s).)

This study aims to evaluate the association between free triiodothyronine (FT3) and outcomes of coronary artery disease (CAD) patients, as well as to assess the predictive power of FT3 and related functional markers from the perspective of potential mechanism. A total of 5104 CAD patients with an average follow-up of three years were enrolled into our study. Multivariate Cox regression was used to evaluate the associations between FT3, FT4 (free thyroxin), FT3/FT4 and death, MACE. We developed and validated an age, biomarker, and clinical history (ABC) model based on FT3 indicators to predict the prognosis of patients with CAD. In the multivariable Cox proportional hazards model, FT3 and FT3/FT4 were independent predictors of mortality (Adjusted HR = 0.624, 95% CI = 0.486-0.801; adjusted HR = 0.011, 95% CI = 0.002-0.07, respectively). Meanwhile, emerging markers pre-brain natriuretic peptide, fibrinogen, and albumin levels are significantly associated with low FT3 ( p < 0.001). The new risk death score based on biomarkers can be used to well predict the outcomes of CAD patients (C index of 0.764, 95% CI = 0.731-0.797). Overall, our findings suggest that low levels of FT3 and FT3/FT4 are independent predictors of death and MACE risk in CAD patients. Besides, the prognostic model based on FT3 provides a useful tool for the death risk stratification of CAD patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tian, Zheng, Liu, Wu, Lin, Chen, Li, Qin, Wang, Zhu, Lai and Zhong.)

Thousands of proteins undergo arginine methylation, a widespread post-translational modification catalyzed by several protein arginine methyltransferases (PRMTs). However, global understanding of their biological functions is limited due to the lack of a complete picture of the catalytic network for each PRMT. Here, we systematically identified interacting proteins for all human PRMTs and demonstrated their functional importance in mRNA splicing and translation. We demonstrated significant overlapping of interactomes of human PRMTs with the known methylarginine-containing proteins. Different PRMTs are functionally redundant with a high degree of overlap in their substrates and high similarities between their putative methylation motifs. Importantly, RNA-binding proteins involved in regulating RNA splicing and translation contain highly enriched arginine methylation regions. Moreover, inhibition of PRMTs globally alternates alternative splicing (AS) and suppresses translation. In particular, ribosomal proteins are extensively modified with methylarginine, and mutations in their methylation sites suppress ribosome assembly, translation, and eventually cell growth. Collectively, our study provides a global view of different PRMT networks and uncovers critical functions of arginine methylation in regulating mRNA splicing and translation., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2021 Science China Press. Published by Elsevier B.V. All rights reserved.)

Aim: To explore the presence and function of NLRP6-caspase 4 inflammasome in human pulp tissue and human dental pulp cells (HDPCs)., Methodology: Pulp tissue was collected from freshly extracted human caries-free third molars and third molars with irreversible pulpitis. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were performed to assess the expression of NLRP6-caspase 4 inflammasome. HDPCs were prepared from normal human pulp tissues and challenged with Porphyromonas gingivalis LPS. Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR were performed to assess if LPS can upregulate NLRP6 and caspase-4. HDPCs were further challenged with LPS followed with cytosolic Streptococcus mutans lipoteichoic acid (LTA). SiRNA targeting NLRP6 and Casp4 and pharmacology inhibitor Ac-FLTD-CMK and MCC950 were used to assess if Streptococcus mutans LTA can activate the NLRP6 but not the NLRP3 inflammasome. Western blot and ELISA were performed to evaluate inflammasome activation. The Student's t-test and one-way anova were used for statistical analysis., Results: NLRP6-caspase 4 inflammasome was upregulated and activated in inflamed human dental pulp tissue. In HDPCs, Porphyromonas gingivalis LPS upregulated the expression of NLRP6, CASP1 and CASP4 in a type I interferon dependent manner. After LPS priming, cytosolic Streptococcus mutans LTA triggered NLRP6-caspase 4 inflammasome activation. Knockdown of NLRP6 or CASP4 using siRNA or using pharmacology inhibitor Ac-FLTD-CMK but not MCC950 efficiently suppressed inflammasome activation by cytosolic LTA., Conclusions: NLRP6-caspase 4 inflammasome may play an important role in pulp inflammation and immune defence. Inflammatory caspases represent a pharmacological target to restrain pulpal inflammation., (© 2020 International Endodontic Journal. Published by John Wiley & Sons Ltd.)