Acid-Promoted Multicomponent Reaction To Synthesize 4-Phosphorylated 4H-Chromenes.

An effective multicomponent reaction for the synthesis of 4-phosphorylated 4H-chromenes via a tandem phosphorylation/alkylation/cyclization/dehydration sequence with water as the only byproduct was developed. Extensive mechanistic investigations involving in situ NMR experiments, time control experiments, and in situ HRMS experiment allowed us to elucidate the order of each subreaction to arrive at a complete understanding of the underlying mechanism of this multicomponent reaction. Mechanistic data confirm that the reaction begins with a phospha-aldol-elimination, followed by addition of a ketone enolate, intermolecular alkylation, intramolecular cyclization, and dehydration under acidic conditions.

MISD-IR: material-image subspace decomposition-based iterative reconstruction with spectrum estimation for dual-energy computed tomography.

Background: Dual-energy computed tomography (DECT) is a promising technique, which can provide unique capability for material quantification. The iterative reconstruction of material maps requires spectral information and its accuracy is affected by spectral mismatch. Simultaneously estimating the spectra and reconstructing material maps avoids extra workload on spectrum estimation and the negative impact of spectral mismatch. However, existing methods are not satisfactory in image detail preservation, edge retention, and convergence rate. The purpose of this paper was to mine the similarity between the reconstructed images and the material images to improve the imaging quality, and to design an effective iteration strategy to improve the convergence efficiency. Methods: The material-image subspace decomposition-based iterative reconstruction (MISD-IR) with spectrum estimation was proposed for DECT. MISD-IR is an optimized model combining spectral estimation and material reconstruction with fast convergence speed and promising noise suppression capability. We proposed to reconstruct the material maps based on extended simultaneous algebraic reconstruction techniques and estimation of the spectrum with model spectral. To stabilize the iteration and alleviate the influence of errors, we introduced a weighted proximal operator based on the block coordinate descending algorithm (WP-BCD). Furthermore, the reconstructed computed tomography (CT) images were introduced to suppress the noise based on subspace decomposition, which relies on non-local regularization to prevent noise accumulation. Results: In numerical experiments, the results of MISD-IR were closer to the ground truth compared with other methods. In real scanning data experiments, the results of MISD-IR showed sharper edges and details. Compared with other one-step iterative methods in the experiment, the running time of MISD-IR was reduced by 75%. Conclusions: The proposed MISD-IR can achieve accurate material decomposition (MD) without known energy spectrum in advance, and has good retention of image edges and details. Compared with other one-step iterative methods, it has high convergence efficiency.

Reprogrammed IDO-Induced Immunosuppressive Microenvironment Synergizes with Immunogenic Magnetothermodynamics for Improved Cancer Therapy.

Indoleamine 2,3-dioxygenase (IDO), highly expressed in hepatocellular carcinoma (HCC), plays a pivotal role in creating an immune-suppressive tumor microenvironment. Inhibiting IDO activity has emerged as a promising immunotherapeutic strategy; however, the delivery of IDO inhibitors to the tumor site is constrained, limiting their therapeutic efficacy. In this study, we developed a magnetic vortex nanodelivery system for the targeted delivery of the IDO inhibitor NLG919, integrated with magnetic hyperthermia therapy to reverse the immune-suppressive microenvironment of liver cancer and inhibit tumor growth. This system comprises thermoresponsive polyethylenimine-coated ferrimagnetic vortex-domain iron oxide nanorings (PI-FVIOs) loaded with NLG919 (NLG919/PI-FVIOs). Under thermal effects, NLG919 can be precisely released from the delivery system, counteracting IDO-mediated immune suppression and synergizing with NLG919/PI-FVIOs-mediated magnetothermodynamic (MTD) therapy-induced immunogenic cell death (ICD), resulting in effective HCC suppression. In vivo studies demonstrate that this combination therapy significantly inhibits tumor growth and metastasis by enhancing the accumulation of cytotoxic T lymphocytes and suppressing regulatory T cells within the tumor. Overall, our findings reveal that NLG919/PI-FVIOs can induce a potent antitumor immune response by disrupting the IDO pathway and activating the ICD, offering a promising therapeutic avenue for HCC treatment.

Clinical characteristics and risk factors in patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases.

Objective: To investigate the clinical characteristics and risk factors of patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases. Methods: A retrospective analysis of general clinical data was conducted on patients with SARS-CoV-2 omicron infection complicated with hypertension, coronary heart disease, and heart failure admitted to one hospital in Guangdong Province from December 1, 2022, to February 28, 2023. Clinical symptoms, laboratory tests, imaging examinations, treatment, and clinical outcomes were collected. Multivariate logistic regression analysis was used to analyze the risk factors for mortality in patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases. ROC curves were drawn to evaluate the predictive value of CRP, D-dimer, and CK-MB in predicting the risk of death. Results: A total of 364 confirmed cases were included, divided into the asymptomatic group, mild to moderate group, and severe to critically ill group based on the symptoms of COVID-19. There were 216 males (59.34%) and 148 females (40.66%), with a median age of 75 years. The differences between the three groups in terms of sex and age were statistically significant (p < 0.05). The top three underlying diseases were hypertension (288 cases, 79.12%), coronary heart disease (100 cases, 27.47%), and diabetes (84 cases, 23.08%). The differences in unvaccinated and triple-vaccinated patients among the three groups were statistically significant (p < 0.05). The common respiratory symptoms were cough in 237 cases (65.11%) and sputum production in 199 cases (54.67%). In terms of laboratory tests, there were statistically significant differences in neutrophils, lymphocytes, red blood cells, C-reactive protein, D-dimer, aspartate aminotransferase, and creatinine among the three groups (p < 0.05). In imaging examinations, there were statistically significant differences among the three groups in terms of unilateral pulmonary inflammation, bilateral pulmonary inflammation, and bilateral pleural effusion (p < 0.05). There were statistically significant differences among the three groups in terms of antibiotic treatment, steroid treatment, oxygen therapy, nasal cannula oxygen inhalation therapy, non-invasive ventilation, and tracheal intubation ventilation (p < 0.05). Regarding clinical outcomes, there were statistically significant differences among the three groups in terms of mortality (p < 0.05). Multivariate logistic regression analysis showed that CRP (OR = 1.012, 95% CI = 1.004-1.019) and D-dimer (OR = 1.117, 95% CI = 1.021-1.224) were independent risk factors for patient mortality. The predictive value of CRP, D-dimer, and CK-MB for the risk of death was assessed. D-dimer had the highest sensitivity (95.8%) in predicting patient mortality risk, while CRP had the highest specificity (84.4%). Conclusion: For patients with COVID-19 and concomitant cardiovascular diseases without contraindications, early administration of COVID-19 vaccines and booster shots can effectively reduce the mortality rate of severe cases. Monitoring biomarkers such as CRP, D-dimer, and CK-MB and promptly providing appropriate care can help mitigate the risk of mortality in patients.

Causal association between type 2 diabetes mellitus and acute suppurative otitis media: insights from a univariate and multivariate Mendelian randomization study.

Background: Type 2 diabetes mellitus (T2DM) and hearing loss (HL) constitute significant public health challenges worldwide. Recently, the association between T2DM and HL has aroused attention. However, possible residual confounding factors and other biases inherent to observational study designs make this association undetermined. In this study, we performed univariate and multivariable Mendelian Randomization (MR) analysis to elucidate the causal association between T2DM and common hearing disorders that lead to HL. Methods: Our study employed univariate and multivariable MR analyses, with the Inverse Variance Weighted method as the primary approach to assessing the potential causal association between T2DM and hearing disorders. We selected 164 and 9 genetic variants representing T2DM from the NHGRI-EBI and DIAGRAM consortium, respectively. Summary-level data for 10 hearing disorders were obtained from over 500,000 participants in the FinnGen consortium and MRC-IEU. Sensitivity analysis revealed no significant heterogeneity of instrumental variables or pleiotropy was detected. Results: In univariate MR analysis, genetically predicted T2DM from both sources was associated with an increased risk of acute suppurative otitis media (ASOM) (In NHGRI-EBI: OR = 1.07, 95% CI: 1.02-1.13, P = 0.012; In DIAGRAM: OR = 1.14, 95% CI: 1.02-1.26, P = 0.016). Multivariable MR analysis, adjusting for genetically predicted sleep duration, alcohol consumption, body mass index, and smoking, either individually or collectively, maintained these associations. Sensitivity analyses confirmed the robustness of the results. Conclusion: T2DM was associated with an increased risk of ASOM. Strict glycemic control is essential for the minimization of the effects of T2DM on ASOM.

Augmented-reality-based surgical navigation for endoscope retrograde cholangiopancreatography: A phantom study.

BACKGROUND: Endoscope retrograde cholangiopancreatography is a standard surgical treatment for gallbladder and pancreatic diseases. However, surgeons is at high risk and require sufficient surgical experience and skills. METHODS: (1) The simultaneous localisation and mapping technique to reconstruct the surgical environment. (2) The preoperative 3D model is transformed into the intraoperative video environment to implement the multi-modal fusion. (3) A framework for virtual-to-real projection based on hand-eye alignment. For the purpose of projecting the 3D model onto the imaging plane of the camera, it uses position data from electromagnetic sensors. RESULTS: Our AR-assisted navigation system can accurately guide physicians, which means a distance of registration error to be restricted to under 5 mm and a projection error of 5.76 ± 2.13, and the intubation procedure is done at 30 frames per second. CONCLUSIONS: Coupled with clinical validation and user studies, both the quantitative and qualitative results indicate that our navigation system has the potential to be highly useful in clinical practice.

A hyaluronic acid hydrogel as a mild photothermal antibacterial, antioxidant, and nitric oxide release platform for diabetic wound healing.

Hyaluronic acid (HA)-based biopolymer hydrogels are promising therapeutic dressings for various wounds but still underperform in treating diabetic wounds. These wounds are extremely difficult to heal and undergo a prolonged and severe inflammatory process due to bacterial infection, overexpression of reactive oxygen species (ROS), and insufficient synthesis of NO. In this study, a dynamic crosslinked hyaluronic acid (HA) hydrogel dressing (Gel-HAB) loaded with allomelanin (AMNP)-N, N'-dis-sec-butyl-N, N'-dinitroso-1, 4-phenylenediamine (BNN6) nanoparticles (AMNP-BNN6) was developed for healing diabetic wounds. The dynamic acylhydrazone bond formed between hydrazide-modified HA (HA-ADH) and oxidized HA (OHA) makes the hydrogel injectable, self-healing, and biocompatible. The hydrogel, loaded with AMNP-BNN6 nanoparticles, exhibits promising ROS scavenging ability and on-demand release of nitric oxide (NO) under near-infrared (NIR) laser irradiation to achieve mild photothermal antibacterial therapy (PTAT) (∼ 48 °C). Notably, the Gel-HAB hydrogel effectively reduced the oxidative stress level, controlled infections, accelerated vascular regeneration, and promoted angiogenesis, thereby achieving rapid healing of diabetic wounds. The injectable self-healing nanocomposite hydrogel could serve as a mild photothermal-enhanced antibacterial, antioxidant, and nitric oxide release platform for the treatment of diabetic wounds.

External Guide Sequence Effectively Suppresses the Gene Expression and Replication of Herpes Simplex Virus 2.

Ribonuclease P (RNase P) complexed with an external guide sequence (EGS) represents a promising nucleic acid-based gene targeting approach for gene expression knock-down and modulation. The RNase P-EGS strategy is unique as an EGS can be designed to basepair any mRNA sequence and recruit intracellular RNase P for hydrolysis of the target mRNA. In this study, we provide the first direct evidence that the RNase P-based approach effectively blocks the gene expression and replication of herpes simplex virus 2 (HSV-2), the causative agent of genital herpes. We constructed EGSs to target the mRNA encoding HSV-2 single-stranded DNA binding protein ICP8, which is essential for viral DNA genome replication and growth. In HSV-2 infected cells expressing a functional EGS, ICP8 levels were reduced by 85%, and viral growth decreased by 3000 folds. On the contrary, ICP8 expression and viral growth exhibited no substantial differences between cells expressing no EGS and those expressing a disabled EGS with mutations precluding RNase P recognition. The anti-ICP8 EGS is specific in targeting ICP8 because it only affects ICP8 expression but does not affect the expression of the other viral immediate-early and early genes examined. This study shows the effective and specific anti-HSV-2 activity of the RNase P-EGS approach and demonstrates the potential of EGS RNAs for anti-HSV-2 applications.

Association between incorrect postures and curve magnitude of adolescent idiopathic scoliosis in china.

BACKGROUND: Despite advancements in school scoliosis screening (SSS), there are still no effective indicators to estimate the severity of spinal curvature. We aim to investigate the association between incorrect postures and curve magnitude of adolescent idiopathic scoliosis (AIS) among Chinese adolescents. METHODS: In this SSS program, we examined the incorrect posture, Adam's forward bending test (FBT) results, and angle of trunk rotation (ATR) in adolescents. Those with suspected scoliosis were referred for a standing anteroposterior whole-spine radiography as outpatients. The radiographic data of 426 students with lateral Cobb angles were collected from 2016 to 2022 and the associations were studied using logistic regression (LR) models and receiver operating characteristic (ROC) curves. RESULTS: Univariate LR revealed that female gender [odds ratio (OR) = 2.92, 95% confidence interval (CI) 1.67-5.09, P < 0.001], age 16-19y (OR = 2.83, 95%CI 1.10-7.28, P = 0.031), right shoulder height (OR = 2.15, 95%CI 1.23-3.75, P = 0.007), right scapula tilt (OR = 2.03, 95%CI 1.18-3.50, P = 0.010), right rib hump (OR = 1.88, 95%CI 1.23-2.85, P = 0.003), right thoracic rotation ≥ 5° (OR = 2.14, 95%CI 1.43-3.20, P < 0.001), and left thoracolumbar kyphosis (OR = 3.79, 95%CI 1.06-13.56, P = 0.041) were all significantly associated with the severity of the curve magnitude. Multivariate LR showed that female gender [adjusted OR (AOR) = 3.23, 95%CI 1.81-5.73, P < 0.001], those aged 16-19y (AOR = 5.08, 95%CI 1.86-13.91, P = 0.002), and with a right rib hump (AOR = 1.72, 95%CI 1.11-2.64, P = 0.015) presented with a higher risk of severe curve magnitude than men, those aged 7-12y, and without a rib hump, respectively. ROC curves further proved that sex, age, shoulder-height difference, scapula tilt, flat back, rib hump, angle of thoracic rotation were the risk predictors for curve magnitude. CONCLUSION: Incorrect posture and ATR, especially the right rib hump, were significantly associated with the curve magnitude of AIS. Early screening for incorrect postures and ATR could be an effective and economical strategy to predict the severity of AIS through SSS in Chinese adolescents.

Association of dietary habits with body mass index and waist circumference, and their interaction effect on hypertension.

Dietary modifications play a crucial role in blood pressure management, and although body mass index (BMI) and waist circumference (WC) are significant predictors of hypertension, limited studies have explored their relationship with dietary habits. This cross-sectional study conducted in Ganzhou, China, focused on middle-aged and elderly residents to investigate the correlation between dietary habits and BMI, WC, and their interaction impact on hypertension. The study found that salty and sweet intake correlated positively with BMI and WC, whereas bean and coarse grain intake were negatively correlated. A significant interaction effect was showed between dietary habits, and BMI and WC on hypertension. Specifically, individuals with obesity or central obesity combined with poor dietary habits had higher odds of hypertension. This study aims to provide a theoretical basis for nutritional interventions for middle-aged and elderly residents with varying obesity levels for the prevention and treatment of hypertension at the community level. The study concluded that dietary habits are significantly associated with BMI and WC, and poor dietary habits coexistence with obesity or central obesity can increase the prevalence rate of hypertension. Understanding these relationships can help develop strategies to address hypertension through dietary and lifestyle changes, providing valuable insights for healthcare professionals and policymakers to develop effective interventions addressing this growing global health concern.

[Preparation and characterization of co-loaded indocyanine green and elemene nano-emulsion in situ gel and its effect on proliferation of breast cancer MCF-7 cells].

This study aims to prepare co-loaded indocyanine green(ICG) and elemene(ELE) nano-emulsion(NE) in situ gel(ICG-ELE-NE-gel) and evaluate its physicochemical properties and antitumor activity in vitro. ICG-ELE-NE-gel was prepared by aqueous phase titration and cold solution methods, followed by characterization of the morphology, particle size, corrosion, and photothermal conversion characteristics. The human breast cancer MCF-7 cells were taken as the model, combined with 808 nm laser irradia-tion. Cell inhibition rate test and cell uptake test were performed. ICG-ELE-NE was spherical and uniform in size. The average particle size and Zeta potential were(85.61±0.35) nm and(-21.4±0.6) mV, respectively. The encapsulation efficiency and drug loading rate were 98.51%±0.39% and 10.96%±0.24%, respectively. ICG-ELE-NE-gel had a good photothermal conversion effect and good photothermal stability. The dissolution of ICG-ELE-NE-gel had both temperature and pH-responsive characteristics. Compared with free ELE, ICG-ELE-NE-gel combined with near-infrared light irradiation significantly enhanced the inhibitory effect on MCF-7 cells and could be uptaken in large amounts by MCF-7 cells. ICG-ELE-NE-gel was successfully prepared, and its antitumor activity was enhanced after 808 nm laser irradiation.

[Correlations between tanshinones and soil factors of Salviae Miltiorrhizae Radix et Rhizoma from different producing areas].

Soil nutrients and inorganic elements affect not only the growth and development of medicinal plants but also the formation and accumulation of active ingredients in traditional Chinese medicines. The content of tanshinones and 28 inorganic elements in Salviae Miltiorrhizae Radix et Rhizoma samples from 18 producing areas in 6 provinces was determined, and 35 physical and chemical properties of the corresponding soil samples were determined. The enrichment characteristics of inorganic elements in Salviae Miltiorrhizae Radix et Rhizoma were analyzed. The correlation analysis and stepwise regression analysis were performed to screen out the main soil factors affecting the content of tanshinones in Salviae Miltiorrhizae Radix et Rhizoma. The results showed that the content of tanshinones in the samples from different areas varied significantly, being the highest in the samples from Shandong, the second in the samples from Henan, and low in the samples from Shanxi and Sichuan. K, Mg, Ca, and Na were rich in Salviae Miltiorrhizae Radix et Rhizoma samples, among which Na and K had the highest enrichment coefficients. The results of correlation and regression analyses showed that soil K, Na, Ti, and total nitrogen were the main soil factors affecting the tanshinones in Salviae Miltiorrhizae Radix et Rhizoma. Specifically, the content of tanshinones was positively correlated with Ti and negatively correlated with Na, K, and total nitrogen in the soil. Therefore, during the planting of Salvia miltiorrhiza, the land should be selected with full consideration to the salinity and saline land should be avoided. Secondly, the application of nitrogen and potassium fertilizers can be appropriately reduced, and water-soluble elemental fertilizers for S. miltiorrhiza should be developed.

Investigating oral microbiome profiles in patients with cleft lip and palate compared with the healthy control.

BACKGROUND: Patients with cleft lip and palate (CLP) have an oronasal communication differed from the closed state in healthy individuals, leading to a unique oral microbiome. This study aimed to determine if variances in the oral microbiota persist among CLP patients who have received treatments for the closure of these fistulas compared to the microbiota of healthy individuals. METHODS: Saliva samples were collected from a cohort comprising 28 CLP patients (CLP group) and 30 healthy controls (HC group). Utilizing 16S rRNA sequencing on the Illumina NovaSeq platform, we conducted a comprehensive analysis of the diversity and composition of the oral microbiota. RESULTS: The analysis of the microbiota in the saliva samples revealed a total of 23 microbial phyla, 38 classes, 111 orders, 184 families, 327 genera and 612 species. The alpha diversity with microbial abundance and evenness indicated the significant difference between the CLP and HC groups. Principal coordinate analysis (PCoA) and the ADONIS test further supported the presence of distinct microorganisms between the two groups. The CLP group displayed elevated abundances of Neisseria, Haemophilus, Porphyromonas, and Granulicatella, as indicated by LefSe analysis. Conversely, Rothia, Veillonella, and Pauljensenia exhibited significant reductions in abundance in the CLP group. The results of the PICRUSt analysis indicated significant differences in the relative abundance of 25 KEGG pathways within the CLP group. Through Spearman correlation analysis, strong associations between Rothia, Veillonella, and Pauljensenia and 25 functional pathways linked to CLP were identified. CONCLUSION: Findings of this study offer a thorough comprehension of the microbiome profiles of CLP patients after the restoration of oronasal structure and are anticipated to present innovative concepts for the treatment of CLP.

Social media use and its impact on adult's mental health and well-being: A scoping review.

BACKGROUND: Social media use has grown in importance and prevalence, with its estimated number of users at 4.9 billion worldwide. Social media use research has revealed positive and negative impacts on users' mental health and well-being. However, such impacts among adults have not been examined in any reviews. METHODS: A scoping review was conducted based on the framework by Arksey and O'Malley and reported based on the PRISMA-ScR guidelines. Eight databases were searched from 2005 to December 2021. Articles were included after being reviewed by three independent teams, with discrepancies resolved through consensus with the senior author. Publication-related information (i.e., authors, year of publication, aims, study population, methodology, interventions, comparisons, outcome measures and key findings) were extracted from each study. Thematic analysis was conducted to answer the research questions. RESULTS: Among the 114 eligible articles, young adults (69.6%) represented the main age group. Most studies (78.6%) focused on the negative impacts of social media use on mental health and well-being, with nearly a third (32.1%) assessing such impacts on depression. Notably, this scoping review found that more than three-quarters (78.6%) of the included studies revealed that excessive and passive social media use would increase depression, anxiety, mood, and loneliness. Nevertheless, a third (33.0%) also reported positive impacts, where positive and purposeful use of social media would contribute to improvements in mental health and well-being, such as increased perceived social support and enjoyment. LINKING EVIDENCE TO ACTION: This review has provided an overview of the existing knowledge on how social media use would affect adults and identified areas of research that merit investigations in future studies. More attention should be given to maximizing the positive impacts of social media use on mental health and well-being among adults.

Educational interventions to reduce depression and anxiety in older adults with cancer in the community: a systematic review, meta-analysis and meta-regression of randomised controlled trials.

BACKGROUND: Older adults make up half of those with cancer and are prone to mood disorders, such as depression and severe anxiety, resulting in negative repercussions on their health-related quality-of-life (HRQOL). Educational interventions have been shown to reduce adverse psychological outcomes. We examined the effect of educational interventions on the severity of psychological outcomes in older adults with cancer (OAC) in the community. METHOD: This PRISMA-adherent systematic review involved a search of PubMed, MedLine, Embase and PsycINFO for randomised controlled trials (RCTs) that evaluated educational interventions impacting the severity of depression, anxiety and HRQOL in OAC. Random effects meta-analyses and meta-regressions were used for the primary analysis. RESULTS: Fifteen RCTs were included. Meta-analyses showed a statistically insignificant decrease in the severity of depression (SMD = -0.30, 95%CI: -0.69; 0.09), anxiety (SMD = -0.30, 95%CI: -0.73; 0.13) and improvement in overall HRQOL scores (SMD = 0.44, 95%CI: -0.16; 1.04). However, subgroup analyses revealed that these interventions were particularly effective in reducing the severity of depression and anxiety in specific groups, such as OAC aged 60-65, those with early-stage cancer, those with lung cancer and those treated with chemotherapy. A systematic review found that having attained a higher education and income level increased the efficacy of interventions in decreasing the severity of adverse psychological outcomes. CONCLUSION: Although overall meta-analyses were statistically insignificant, subgroup meta-analyses highlighted a few specific subgroups that the educational interventions were effective for. Future interventions can be implemented to target these vulnerable groups.

Recombinant fibroblast growth factor 4 ameliorates axonal regeneration and functional recovery in acute spinal cord injury through altering microglia/macrophage phenotype.

Neuroinflammation is one of the extensive secondary injury processes that aggravate metabolic and cellular dysfunction and tissue loss following spinal cord injury (SCI). Thus, an anti-inflammatory strategy is crucial for modulating structural and functional restoration during the stage of acute and chronic SCI. Recombinant fibroblast growth factor 4 (rFGF4) has eliminated its mitogenic activity and demonstrated a metabolic regulator for alleviating hyperglycemia in type 2 diabetes and liver injury in non-alcoholic steatohepatitis. However, it remains to be explored whether or not rFGF4 has a neuroprotective effect for restoring neurological disorders, such as SCI. Here, we identified that rFGF4 could polarize microglia/macrophages into the restorative M2 subtype, thus exerting an anti-inflammatory effect to promote neurological functional recovery and nerve fiber regeneration after SCI. Importantly, these effects by rFGF4 were related to triggering PI3K/AKT/GSK3ß and attenuating TLR4/NF-κB signaling axes. Conversely, gene silencing of the PI3K/AKT/GSK3ß signaling or pharmacological reactivation of the TLR4/NF-κB axis aggravated inflammatory reaction. Thus, our findings highlight rFGF4 as a potentially therapeutic regulator for repairing SCI, and its outstanding effect is associated with regulating macrophage/microglial polarization.

Targeting SAT1 prevents osteoporosis through promoting osteoclast apoptosis.

Osteoporosis is a systemic bone disease characterized by decreased bone mass that is tightly regulated by the coordinated actions of osteoclasts and osteoblasts. Apoptosis as a precise programmed cell death involves a cascade of gene expression events which are mechanistically linked to the regulation of bone metabolism. Nevertheless, the critical biomolecules involved in regulating cell apoptosis in osteoporosis remain unknown. To gain a deeper insight into the relationship between apoptosis and osteoporosis, this study integrated the sequencing results of human samples and using a machine learning workflow to overcome the limitations of a single study. Among all immune cell populations, we assessed the apoptotic level and portrayed the distinct subtypes and lineage differentiation of monocytic cells in osteoporotic tissues. Osteoclasts expressed a higher level of Spermidine/spermine-N1-Acetyltransferase1 (SAT1) during osteoclastogenesis which prevented osteoclasts apoptosis and facilitate osteoporosis progression. In addition, Berenil, one potent SAT1 inhibitor, increased osteoclast apoptosis and reversed the bone loss in the femurs of a murine ovariectomy model. In summary, Berenil promotes osteoclast apoptosis, inhibits the bone resorption and improves the abnormal bone structure in vitro and in vivo models by targeting SAT1, demonstrating its potential as a precise therapeutic strategy for clinical osteoporosis treatment.

Hyaluronic acid-based multifunctional bio-active coating integrated with cinnamaldehyde/hydroxypropyl-ß-cyclodextrin inclusion complex for fruit preservation.

Natural preservatives such as cinnamaldehyde (CIN) are garnering increasing interest to replace their synthetic counterparts in maintaining fruit freshness and safety. However, their long-term effectiveness and widespread application have been greatly limited due to high volatility and potent aroma. To address these challenges, we developed a viable and simple strategy to prepare a multifunctional active coating for fruit preservation by incorporating host-guest inclusion complex of CIN and 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) CIN@HP-ß-CD into hyaluronic acid (HA), a natural polysaccharide with exceptional film-forming properties. The as-prepared HA/CIN@HP-ß-CD coatings exhibited universal surface affinity, excellent antimicrobial performance, and satisfactory antioxidant properties with no potential toxicity. Release kinetic studies have demonstrated that CIN in the coating is continuously and slowly released. Furthermore, freshness preservation experiments on bananas and fresh-cut apples demonstrated that the developed coating is effective in preserving the color of fruit, decreasing the weight loss rate, preventing the microorganism's growth, and significantly extending the period of freshness, exhibiting the potential for application in fruit preservation.

The preparation of gallic acid-grafted cationic chitosan as effective salt-tolerant flocculants.

In this work, gallic acid was successfully grafted onto quaternary aminated chitosan to prepare a high efficiency cationic flocculant. The mechanism of flocculation and different influencing factors were studied in detail. The prepared flocculant only needs 60 mg L-1 to achieve a 98.7% and 94.5% removal rate on methyl blue (MB) and Congo red (CR), respectively. The high removal rate (93.2%) of a CR-MB mixed dye also confirms the universality of flocculation. In addition, kaolin as a simulated suspended solid was removed at a rate of 97% in the experiment at a dosage of 3 mg L-1. A zeta potential test showed that it worked best when the potential of the flocculation system was zero; this was because an electrostatic balance was reached between the flocculant and pollutant. Importantly, the three-functional molecules can provide more possibilities to form hydrogen bonds with water molecules, which is conducive to the stretching of flocculant molecular chains in salt water. The flocculant maintained a high stability in four different salt environments and has a positive industrial application significance. Furthermore, the flocculation experiment of the actual wastewater of the printing and dyeing plant found that the dye wastewater changed obviously from turbidity to clarification, which proved the practical application potential of the flocculant. This work provides a feasible idea for the preparation of bio-based flocculants.