DDAH1 promotes neurogenesis and neural repair in cerebral ischemia.

Choline acetyltransferase (ChAT)-positive neurons in neural stem cell (NSC) niches can evoke adult neurogenesis (AN) and restore impaired brain function after injury, such as acute ischemic stroke (AIS). However, the relevant mechanism by which ChAT+ neurons develop in NSC niches is poorly understood. Our RNA-seq analysis revealed that dimethylarginine dimethylaminohydrolase 1 (DDAH1), a hydrolase for asymmetric NG,NG-dimethylarginine (ADMA), regulated genes responsible for the synthesis and transportation of acetylcholine (ACh) (Chat, Slc5a7 and Slc18a3) after stroke insult. The dual-luciferase reporter assay further suggested that DDAH1 controlled the activity of ChAT, possibly through hypoxia-inducible factor 1α (HIF-1α). KC7F2, an inhibitor of HIF-1α, abolished DDAH1-induced ChAT expression and suppressed neurogenesis. As expected, DDAH1 was clinically elevated in the blood of AIS patients and was positively correlated with AIS severity. By comparing the results among Ddah1 general knockout (KO) mice, transgenic (TG) mice and wild-type (WT) mice, we discovered that DDAH1 upregulated the proliferation and neural differentiation of NSCs in the subgranular zone (SGZ) under ischemic insult. As a result, DDAH1 may promote cognitive and motor function recovery against stroke impairment, while these neuroprotective effects are dramatically suppressed by NSC conditional knockout of Ddah1 in mice.

A novel approach to wound healing: Green synthetic nano-zinc oxide embedded with sodium alginate and polyvinyl alcohol hydrogels for dressings.

Wound healing constitutes a formidable challenge within the healthcare system, attributable to infection risks and protracted recovery periods. The pressing need for innovative wound healing methods has spurred the urgency to develop novel approaches. This study sought to advance wound healing by introducing a novel approach employing a composite sponge dressing. The composite sponge dressing, derived from LFL-ZnO (synthesized through the green methodology utilizing Lactobacillus plantarum ZDY2013 fermentation liquid), polyvinyl alcohol (PVA), and sodium alginate (SA) via a freeze-thaw cycle and freeze-drying molding process, demonstrated notable properties. The findings elucidate the commendable swelling, moisturizing, and mechanical attributes of the SA/LFL-ZnO/PVA composite sponge dressing, characterized by a porous structure. Remarkably, the dressing incorporating LFL-ZnO exhibited substantial inhibition against both methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus (S. aureus). Hemolysis and cytotoxicity tests corroborated the excellent biocompatibility of the sponge dressing. In vivo evaluation of the therapeutic efficacy of the 1 mg/mL LFL-ZnO composite dressing on scald wounds and S. aureus-infected wounds revealed its capacity to accelerate wound healing and exert pronounced antibacterial effects. Consequently, the composite sponge dressings synthesized in this study hold significant potential for application in wound treatment.

Mindfulness in ward nurses: A concept analysis.

AIM: Mindfulness has been widely used with all kinds of people, such as students, educators or patients. However, there have been no studies explicitly targeting ward nurses. The aim of this study is to explore the concept analysis of mindfulness in ward nurses. DESIGN: A concept analysis. METHODS: An electronic literature search of MEDLINE, Google Scholar, PubMed, Cambridge Online Dictionary and EBSCO on mindfulness was conducted over a ten-year period of Peer-reviewed scholarly articles published in English. The Walker and Avant's framework was used for this paper. RESULTS: Eleven articles in total were included in this study. Three attributes of mindfulness in ward nurses were identified as in the present moment, paying attention and being receptive. The consequence of mindfulness in ward nurses lead to positive changes, which included improving well-being, decreased burnout, anxiety and depression. An exploration of mindfulness in ward nurses was developed. The findings of this paper can be used in ward nurses, research and administration.

Maternal F-53B exposure during pregnancy and lactation induced glucolipid metabolism disorders and adverse pregnancy outcomes by disturbing gut microbiota in mice.

In the metal plating industry, F-53B has been widely used for almost half a century as a replacement for perfluorooctane sulfonate. However, F-53B can reach the food chain and affect human health. Pregnant women have distinct physiological characteristics and may thus be more sensitive to the toxicity of F-53B. In the present study, F-53B was added to the drinking water of pregnant mice during gestation and lactation at doses of 0 mg/L (Ctrl), 0.57 mg/L (L-F), and 5.7 mg/L (H-F). The aim was to explore the potential effects of F-53B on glucolipid metabolism and pregnancy outcomes in dams. Results showed that F-53B induced disordered glucolipid metabolism, adverse pregnancy outcomes, hepatic inflammation, oxidative stress and substantially altered related biochemical parameters in maternal mice. Moreover, F-53B induced remarkable gut barrier damage and gut microbiota perturbation. Correlation analysis revealed that gut microbiota is associated with glucolipid metabolism disorders and hepatic inflammation. The fecal microbiota transplant experiment demonstrated that altered gut microbiota induced by F-53B caused metabolic disorders, adverse pregnancy outcomes, and gut barrier damage. These results suggested that maternal mice exposed to F-53B during gestation and lactation had an increased risk of developing metabolic disorders and adverse pregnancy outcomes and highlighted the crucial role of the gut microbiota in this process, offering novel insights into the risk of F-53B to health.

Co-exposure with cadmium elevates the toxicity of microplastics: Trojan horse effect from the perspective of intestinal barrier.

Microplastics (MPs) have been shown to adsorb heavy metals and serve as vehicles for their environmental transport. To date, insufficient studies have focused on enterohepatic injury in mice co-exposed to both MPs and cadmium (Cd). Here, we report that Cd adsorption increased the surface roughness and decreased the monodispersity of PS-MPs. Furthermore, exposure to both PS-MPs and Cd resulted in a more severe toxic effect compared to single exposure, with decreased body weight gain, shortened colon length, and increased colonic and hepatic inflammatory response observed. This can be attributed to an elevated accumulation of Cd resulting from increased gut permeability, coupled with the superimposed effects of oxidative stress. In addition, using 16 S sequencing and fecal microbiota transplantation, it was demonstrated that gut microbiota dysbiosis plays an essential role in the synergistic toxicity induced by PS-MPs and Cd in mice. This study showed that combined exposure to MPs and Cd induced more severe intestinal and liver damage in mice compared to individual exposure, and provided a new perspective for a more systematic risk assessment process related to MPs exposure.

Prognostic significance of serum monoclonal proteins based on immunofixation electrophoresis in B-cell non-Hodgkin lymphoma.

The presence of serum monoclonal components has been associated with poor outcomes in various hematological malignancies. The current study focused on exploring its prognostic role in B-cell non-Hodgkin lymphoma. Our study represented 314 patients with information on serum immunofixation electrophoresis at diagnosis that were available with B-cell non-Hodgkin lymphoma. IFE was positive in 61 patients (19%). Baseline features were comparable between pairs of groups, poor ECOG PS, B symptoms, advanced stage, and high-risk IPI score were significantly more frequent in the + IFE group. Shorter PFS and OS of B-NHL patients were observed in patients who presented at diagnosis with a + IFE, and IFE was the independent predictor of PFS and OS in multivariate analysis. Moreover, integrating IFE into the IPI-M1, IPI-M2, and IPI-M3 models improved the area under the curve for more accurate survival prediction and prognosis. Serum monoclonal proteins are significant prognostic indicators for newly diagnosed B-cell non-Hodgkin lymphoma that can early identify patients with poor prognosis and guide clinical treatment decisions.

Enhancing cranial defect repair in rats: investigating the effect of combining Total Flavonoids from Rhizoma Drynariae with calcium phosphate/collagen scaffolds.

OBJECTIVE: To investigate the therapeutic efficacy of total flavonoids of Rhizoma Drynariae (TFRD) in conjunction with a calcium phosphate/collagen scaffold for the repair of cranial defects in rats. METHODS: The subjects, rats, were segregated into four groups: Control, TFRD, Scaffold, and TFRD + Scaffold. Cranial critical bone defects, 5 mm in diameter, were artificially induced through precise drilling. Post-surgery, at intervals of 2, 4, and 8 weeks, micro-CT scans were conducted to evaluate the progress of skull repair. Hematoxylin-eosin and Masson staining techniques were applied to discern morphological disparities, and immunohistochemical staining was utilized to ascertain the expression levels of local osteogenic active factors, such as bone morphogenetic protein 2 (BMP-2) and osteocalcin (OCN). RESULTS: Upon examination at the 8-week mark, cranial defects in the Scaffold and TFRD + Scaffold cohorts manifested significant repair, with the latter group displaying only negligible foramina. Micro-CT examination unveiled relative to its counterparts, and the TFRD + Scaffold groups exhibited marked bone regeneration at the 4- and 8-week intervals. Notably, the TFRD + Scaffold group exhibited substantial bone defect repair compared to the TFRD and Scaffold groups throughout the entire observation period, while histomorphological assessment demonstrated a significantly higher collagen fiber content than the other groups after 2 weeks. Immunohistochemical analysis further substantiated that the TFRD + Scaffold had augmented expression of BMP-2 at 2, 4 weeks and OCN at 2 weeks relative to other groups. CONCLUSIONS: The synergistic application of TFRD and calcium phosphate/collagen scaffold has been shown to enhance bone mineralization, bone plasticity, and bone histomorphology especially during initial osteogenesis phases.

Indole-3-acetamide from gut microbiota activated hepatic AhR and mediated the remission effect of Lactiplantibacillus plantarum P101 on alcoholic liver injury in mice.

Alcoholic liver disease is a prevalent condition resulting from excessive alcohol consumption, characterized by hepatic lipid accumulation and inflammation. This study delved into the protective effects and mechanisms of L. plantarum P101 on alcoholic liver injury in mice. As a result, L. plantarum P101 intervention reduced ALT and AST release, indicative of hepatocyte injury alleviation, while enhancing the activity of the antioxidant enzymes SOD and CAT. A reduction in pro-inflammatory cytokine TNF-α and an increase in anti-inflammatory cytokine IL-10 levels were observed in the L. plantarum P101-intervened mouse liver, signifying reduced inflammation within the mice. Furthermore, L. plantarum P101 intervention altered the gut microbial composition, primarily marked by an increase in Bacteroidota abundance, along with significant enrichment of beneficial bacteria, including Coprostanoligenes, Blautia and Lactiplantibacillus. Correlation analysis unveiled connections between serum tryptophan metabolites and the altered gut microbiota genera, suggesting that gut microbiota-driven effects may extend to extraintestinal organs through their metabolites. Intriguingly, serum indole-3-acetamide (IAM) was elevated by L. plantarum P101-regulated gut microbiota. Subsequently, the role of IAM in ameliorating alcoholic injury was explored using HepG2 cells, where it bolstered cell viability and attenuated EtOH-induced oxidative damage. Concomitantly, IAM activated the gene and protein expression of AhR in cells. Likewise, hepatic AhR expression in mice subjected to L. plantarum P101 significantly up-regulated, possibly instigated by gut microbiota-mediated IAM. Collectively, L. plantarum P101 orchestrates a modulation of gut microbiota and its metabolites, particularly IAM, to activate AhR, thereby alleviating alcoholic liver injury.

The experience of diagnosis and treatment for TAFRO syndrome.

Early identification, diagnosis and treatment of TAFRO syndrome are very importants. We retrospectively analysed 6 patients with TAFRO syndrome. Their clinical manifestations, treatment methods, survival and other aspects were summarized. All patients were pathologically diagnosed with Castleman's disease, with fever, an inflammatory storm state and varying degrees of anasarca. All patients received steroid therapy; four of them also received chemotherapy, and 1 received rituximab. Of the 3 patients with severe disease, only 1 patient who received the recommended dose of glucocorticoids survived. Early administration of glucocorticoids can improve the prognosis, especially in patients with severe disease, and adequate glucocorticoids are important.

Fabrication of cationic cellulose nanofibrils/sodium alginate beads for Congo red removal.

Congo red is hard to remove from dye wastewater due to its structure stability and high chemical oxygen demand. In this study, cationic cellulose nanofibrils (CCNF) prepared from herb residues was physically crosslinked with sodium alginate (SA) in the presence of calcium ions, and the obtained CCNF/SA beads were used to adsorb Congo red. Results showed that CCNF/SA beads with porous internal structure were beneficial to adsorption. The maximum adsorption capacity of Congo red could reach to 518.4 mg/g, which was superior to most cellulose-based adsorption materials. Furthermore, the equilibrium adsorption isotherms and XPS analysis indicated the adsorption for Congo red was a physical process, and hydrogen bond and electrostatic adsorption were proposed as dominant adsorption mechanism. In addition, the Congo red removal efficiency of the beads was still higher than 70% after three cycles. Therefore, this high efficiency and green beads have great potential as adsorbents for anionic dyes removal.

Differences in the effects of orthodontic treatment on airway-craniocervical functional environment in adult and adolescent patients with skeletal class II high-angle: a retrospective pilot study.

INTRODUCTION: This retrospective cohort study aimed to compare the change in upper airway and craniocervical posture after orthodontic treatment between adolescent and adult patients with Class II high-angle malocclusion. METHODS: A total of 12 adolescent (mean ± standard deviation age = 13.0 ± 2.0 years) and 12 adult patients with Class II high-angle malocclusion (mean ± standard deviation age = 23.7 ± 6.4 years) were selected in this study. The lateral cephalograms and cone beam computed tomography images of adolescent and adult patients were taken before and after treatment, which can be employed to evaluate the variables of craniofacial morphology, upper airway, and craniocervical posture through paired t tests, respectively. An independent sample t test was performed to observe the differences between two groups after orthodontic intervention. For adults and adolescents, the correlation between craniofacial morphology, upper airway, and craniocervical posture was determined through Pearson correlation analysis. RESULTS: In all subjects, the improvements in vertical and sagittal facial morphology after treatment were observed. Anterior and inferior movements of the hyoid bone, an increase of upper airway dimension, posterior tipping of the head and a reduction of cervical inclination in the lower and middle segments post-treatment were identified in adolescence (P < 0.05). Adults displayed anterior movements of the hyoid bone, whereas no significant difference was observed in upper airway dimension and craniocervical posture (P < 0.05). Notable differences were identified in the change of hyoid position and airway volume between two groups (P > 0.05). Mandibular plane inclination, growth pattern, occlusal plane inclination, and chin position were all significantly correlated with craniocervical posture in adolescent patients. Besides, the mandibular growth pattern and chin position in adult patients were significantly correlated with craniocervical posture (P < 0.05). CONCLUSIONS: Orthodontic treatment is capable of enhancing the facial profile of patients with skeletal class II high-angle while improving their upper airway morphology and craniocervical posture, where adolescents and adults differ substantially in that the former exhibit a more favorable alteration in the airway-craniocervical functional environment.

MYC overexpression but not MYC/BCL2 double expression predicts survival in bulky mass diffuse large B-cell lymphoma patients.

PURPOSE: The prognostic factors for diffuse large B-cell lymphoma (DLBCL) have been fully explored, but prognostic information for bulky mass DLBCL patients is limited. This study aimed to analyze the prognostic value of MYC protein expression and other biological parameters in bulky mass DLBCL patients. METHODS: We defined a bulky mass as a maximum tumor diameter ≥7.5 cm and studied 227 patients with de novo bulky mass DLBCL. RESULTS: In all patients with bulky mass DLBCL, the 1-year and 3-year OS rates were 72.7% and 57.1%, respectively, and the 1-year and 3-year PFS rates were 52.0% and 42.5%, respectively. The MYC overexpression group (n = 140) showed significantly worse overall survival (OS; p = 0.019) and progression-free survival (PFS; p = 0.001) than the non-MYC overexpression group (n = 87). Subgroup analyses demonstrated that the MYC overexpression group was associated with inferior OS and PFS in the subgroups with the International Prognostic Index score of 3-5 (OS: p = 0.011; PFS: p < 0.001), Ann Arbor stage 3-4 (OS: p = 0.014; PFS: p < 0.001) and GCB subtype (OS: p = 0.014; PFS: p = 0.010). Consolidation radiotherapy improved OS and PFS in patients with bulky mass DLBCL (OS: p = 0.008; PFS: p = 0.004) as well as in those with MYC overexpression (OS: p = 0.001; PFS: p = 0.001). The prognostic value of MYC overexpression was maintained in a multivariate model adjusted for the International Prognostic Index. CONCLUSION: MYC overexpression is a poor predictor for bulky mass DLBCL patients. Consolidation radiotherapy for residual disease after induction therapy may improve outcomes for patients with bulky mass DLBCL.

T-cell dysfunction in natural killer/T-cell lymphoma.

Natural killer/T-cell lymphoma (NKTCL) is an incurable aggressive T-cell lymphoma closely correlated with Epstein‒Barr virus (EBV) infection. Chronic and consistent viral infection induces T-cell exhaustion. Herein, we describe T-cell dysfunction in NKTCL patients for the first time. Peripheral blood mononuclear cells (PBMCs) from age-matched healthy donors (HDs) and NKTCL patients were collected, and lymphocyte distributions, multiple surface inhibitory receptors (IRs), effector cytokine production and cell proliferation were determined by flow cytometry. PBMCs from HDs were cocultured with NKTCL cell lines to verify the clinical findings. IR expression was further assessed in NKTCL tumor biopsies using multiplex immunohistochemistry (mIHC). NKTCL patients have higher frequencies than HDs of inhibitory T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs). T-cell distribution also varies between NKTCL patients and HDs. T cells from NKTCL patients demonstrated higher expression levels of multiple IRs than HDs. Meanwhile, T-cell proliferation and interferon-γ production was significantly reduced in NKTCL patients. More importantly, the number of EBV-specific cytotoxic cells was lower in NTKCL patients, and these cells demonstrated upregulation of multiple IRs and secreted fewer effector cytokines. Interestingly, NKTCL cells caused normal PBMCs to acquire T-cell exhaustion phenotypes and induced generation of Tregs and MDSCs. In line with ex vivo finding, mIHC results showed that CD8+ T cells from NKTCL tumor biopsies expressed much higher level of IRs compared with reactive lymphoid hyperplasia individuals. The immune microenvironment of NKTCL patients exhibited T-cell dysfunction and accumulation of inhibitory cell components, which may contribute to impaired antitumor immunity.

Correlation analysis of anthropometric indices and type 2 diabetes mellitus in residents aged 60 years and older.

Background and purpose: In recent years, the incidence of obesity in people aged 60 and over has increased significantly, and abdominal obesity has been recognized as an independent risk factor for diabetes. Aging causes physiologic decline in multiple body systems, leading to changes in obesity indicators such as BMI. At present, the relationship between abdominal obesity markers and Diabetes mellitus (DM) in people aged 60 years and older remains unclear. Therefore, it is necessary to study the correlation between anthropometric indices and diabetes and explore potential predictors. Methods: The basic demographic information of participants aged 60 and above in Zhongshan City in 2020 was collected. Physical parameters, blood glucose and other biochemical indices were measured comprehensively. Binary logistic regression analysis was used to explore the relationship between abdominal obesity indicators [Waist circumference, Neck Circumference, Waist-to-hip ratio, Chinese Visceral Obesity Index (CVAI), and visceral obesity index] and diabetes mellitus. ROC characteristic curve was used to analyze the predictive ability of abdominal obesity indicators to DM, and the non-restrictive cubic spline graph was used to visualize the screened obesity indicators and diabetes risk. Results: Among 9,519 participants, the prevalence of diabetes was 15.5%. Compared with low CVAI, High CVAI level was significantly associated with increased prevalence of DM in males and females (all p < 0.05), in males (OR, 2.226; 95%CI: 1.128-4.395), females (OR, 1.645; 95%CI: 1.013-2.669). After adjusting for potential confounding factors, there were gender differences between neck circumference and the prevalence of DM, and above-normal neck circumference in males was significantly associated with increased prevalence of DM (OR, 1.381; 95% CI: 1.091-1.747) (p < 0.05). Conclusion: Among these anthropometric indices, CVAI is consistent with the features of fat distribution in older individuals and shows superior discriminative power as a potential predictor of DM, compared to traditional anthropometric parameters.

Omega-3 polyunsaturated fatty acids alleviate early brain injury after traumatic brain injury by inhibiting neuroinflammation and necroptosis.

Presently, traumatic brain injury (TBI) is a leading contributor to disability and mortality that places a considerable financial burden on countries all over the world. Docosahexaenoic acid and eicosapentaenoic acid are two kinds of omega-3 polyunsaturated fatty acids (ω-3 PUFA), both of which have been shown to have beneficial biologically active anti-inflammatory and antioxidant effects. However, the neuroprotective effect of ω-3 PUFA in TBI has not been proven, and its probable mechanism remains obscure. We suppose that ω-3 PUFA can alleviate early brain injury (EBI) via regulating necroptosis and neuroinflammation after TBI. This research intended to examine the neuroprotective effect of ω-3 and its possible molecular pathways in a C57BL/6 mice model of EBI caused by TBI. Cognitive function was assessed by measuring the neuronal necroptosis, neuroinflammatory cytokine levels, brain water content, and neurological score. The findings demonstrate that administration of ω-3 remarkably elevated neurological scores, alleviated cerebral edema, and reduced inflammatory cytokine levels of NF-κB, interleukin-1ß (IL-1ß), IL-6, and TNF-α, illustrating that ω-3 PUFA attenuated neuroinflammation, necroptosis, and neuronal cell death following TBI. The PPARγ/NF-κB signaling pathway is partially responsible for the neuroprotective activity of ω-3. Collectively, our findings illustrate that ω-3 can alleviate EBI after TBI against neuroinflammation and necroptosis.

Digital orthodontic extrusion system for complex crown-root fracture of anterior teeth: A technique report.

Patients with traumatic dental injuries commonly present in clinical practice with complex crown-root fractures. Prosthodontic treatment of such patients may be unsuccessful because of the violation of the supracrestal tissue attachment, making their management challenging. Minor tooth movement is an effective solution to extruding the residual root but may require referral to an orthodontist. The purpose of this technique was to present a digital orthodontic system including a 3-dimensional virtual patient technique, a computer-aided design and computer-aided manufacture (CAD-CAM) resin facial veneer-retained pontic, and a zirconia post as an orthodontic appliance for tooth extrusion in the esthetic zone. This veneered pontic may also serve as an interim prothesis. The appliance provides a precise design for the direction and extent of orthodontic extrusion.

Determination of purines in prepackaged food using optimum acid hydrolysis followed by high performance liquid chromatography.

A high performance liquid chromatography was established to determine purine content of prepackaged food. Chromatographic separation was performed on Agilent5 TC-C18 column. Ammonium formate (10 mmol/L, pH = 3.385) and methanol (99:1) were used as mobile phase. Purine concentration and peak area showed good linear relationships in the range from 1 to 40 mg/L (guanine, hypoxanthine, adenine) and xanthine exhibited a good linear relationship ranged from 0.1 to 4.0 mg/L. Recoveries of four purines ranged from 93.03% to 107.42%. Purine content in prepackaged food was following: animal derived prepackaged food: 16.13-90.18 mg/100 g; beans and bean products: 66.36-157.11 mg/100 g; fruits and fruit products: 5.64-21.79 mg/100 g; instant rice and flour products: 5.68-30.83 mg/100 g; fungi, algae, fungi and algae products: 32.57-70.59 mg/100 g. This proposed method had good precision and accuracy with a wide linear range for detection of purine. Animal derived prepackaged food was purine-rich food, purine content of plant derived prepackaged food varied greatly.

Analysis of the potential biological mechanisms of Danyu Gukang Pill against osteonecrosis of the femoral head based on network pharmacology.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is still a challenge for orthopedists worldwide and can lead to disability if patients are not treated effectively. Danyu Gukang Pill (DGP), a traditional Chinese medicine (TCM) formulation, is recognized to be effective against ONFH. Nevertheless, its molecular mechanisms remain to be clarified. METHODS: The active ingredients of DGP were collected from the online databases according to oral bioavailability (OB) and drug-likeness (DL). The potential targets of DGP were retrieved from the TCMSP database, while the potential targets of ONFH were obtained from the GeneCards and NCBI databases. The functions and signaling pathways of the common targets of DGP and ONFH were enriched by GO and KEGG analyses. Subsequently, molecular docking and in vitro cell experiments were performed to further validate our findings. RESULTS: In total, 244 active ingredients of DGP and their corresponding 317 targets were obtained, and 40 ONFH-related targets were predicted. Afterwards, 19 common targets of DGP and ONFH were obtained and used as potential targets for the treatment of ONFH. Finally, combined with network pharmacology analysis, molecular docking and in vitro cell experiments, our study first demonstrated that the treatment effect of DGP on ONFH might be closely related to the two targets, HIF1A (HIF-1α) and VEGFA, and the HIF-1 signaling pathway. CONCLUSIONS: This study is the first to investigate the molecular mechanisms of DGP in the treatment of ONFH based on network pharmacology. The results showed that DGP might up-regulate the expression of HIF-1α and VEGFA by participating in the HIF-1 signaling pathway, thus playing an anti-ONFH role.

Residues E53, L55, H59, and G70 of the cellular receptor protein Tva mediate cell binding and entry of the novel subgroup K avian leukosis virus.

Subgroup K avian leukosis virus (ALV-K) is a novel subgroup of ALV isolated from Chinese native chickens. As for a retrovirus, the interaction between its envelope protein and cellular receptor is a crucial step in ALV-K infection. Tva, a protein previously determined to be associated with vitamin B12/cobalamin uptake, has been identified as the receptor of ALV-K. However, the molecular mechanism underlying the interaction between Tva and the envelope protein of ALV-K remains unclear. In this study, we identified the C-terminal loop of the LDL-A module of Tva as the minimal functional domain that directly interacts with gp85, the surface component of the ALV-K envelope protein. Further point-mutation analysis revealed that E53, L55, H59, and G70, which are exposed on the surface of Tva and are spatially adjacent, are key residues for the binding of Tva and gp85 and facilitate the entry of ALV-K. Homology modeling analysis indicated that the substitution of these four residues did not significantly impact the Tva structure but impaired the interaction between Tva and gp85 of ALV-K. Importantly, the gene-edited DF-1 cell line with precisely substituted E53, L55, H59, and G70 was completely resistant to ALV-K infection and did not affect vitamin B12/cobalamin uptake. Collectively, these findings not only contribute to a better understanding of the mechanism of ALV-K entry into host cells but also provide an ideal gene-editing target for antiviral study.

Decitabine combined with RDHAP regimen in relapsed/refractory diffuse large B cell lymphoma.

BACKGROUND: There is an urgent need for effective treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (R/R-DLBCL). This trial investigated the efficacy of decitabine in combination with rituximab, cisplatin, cytarabine, dexamethasone (RDHAP) in R/R-DLBCL. METHODS: 56 patients were divided into two groups (decitabine-RDHAP group. n = 35; RDHAP group, n = 21). The primary endpoints were the overall response rate (ORR) and duration of remission (DOR). Secondary objectives were toxicity, progression-free survival (PFS), and overall survival (OS). RESULTS: The ORR was 40% and 33% for decitabine-RDHAP and RDHAP groups, respectively, with no difference between the groups. The DOR for the decitabine-RDHAP regimen was higher than that for the RDHAP regimen (p = 0.044). After a median follow-up of 12.0 months, the median PFS and OS were 7.0 and 17.0 months for in the decitabine-RDHAP group and 5.0 and 9.0 months in the RDHAP group with no significant differences between the two groups (p = 0.47, 0.17). The incidence of adverse events was not significantly different between groups. CONCLUSION: The decitabine-RDHAP regimen is effective and well tolerated, and is a promising salvage regimen for R/R-DLBCL.