Recent advances in host-focused molecular tools for investigating host-gut microbiome interactions.

Microbial communities in the human gut play a significant role in regulating host gene expression, influencing a variety of biological processes. To understand the molecular mechanisms underlying host-microbe interactions, tools that can dissect signaling networks are required. In this review, we discuss recent advances in molecular tools used to study this interplay, with a focus on those that explore how the microbiome regulates host gene expression. These tools include CRISPR-based whole-body genetic tools for deciphering host-specific genes involved in the interaction process, Cre-loxP based tissue/cell-specific gene editing approaches, and in vitro models of host-derived organoids. Overall, the application of these molecular tools is revolutionizing our understanding of how host-microbiome interactions contribute to health and disease, paving the way for improved therapies and interventions that target microbial influences on the host.

Clinical features of non-syndromic late developing supernumerary teeth: a sign of the third dentition?

OBJECTIVES: This study aimed to summarize the clinical features of non-syndromic late developing supernumerary teeth (LDST) and comparisons with common supernumerary teeth (ST) and explore the association between LDST and the third dentition. MATERIALS AND METHODS: This study retrospected cone-beam computed tomography (CBCT) and medical history of 41,903 consecutive patients from January to December 2021. Comparisons between ST and LDST were evaluated by Chi-square test or Fisher exact test. Correlation between chronological age and dental stage age was evaluated by Spearman's rank correlation coefficient. Binary logistic regression analysis was used to explore the features of LDST originating from the third dentition. RESULTS: Sixty patients with 126 non-syndromic LDST and 1602 patients with 1988 non-syndromic ST were identified. The prevalence of ST and LDST was 3.82% and 0.14%, respectively, with a male-female ratio of 1.78:1 and 1.31:1. LDST patients mainly had LDST in multiple (58.33%) and bilaterally (41.67%), with an average of 2.1/patient. Most LDST were normal-shaped (84.13%), vertically oriented (71.43%), located in the mandible (80.16%), and distributed in the premolar region (82.54%). The study also indicated that the development of LDST was correlated with permanent teeth, with LDST developing 6.48 to 10.45 years later. In this study, 72.22% of LDST met the clinical criteria for the third dentition. CONCLUSIONS: LDST manifested different clinical features from common ST. LDST might be closely related to the third dentition. CLINICAL RELEVANCE: This work would help to comprehend LDST from a clinical perspective, and may be complementary to the criteria of the third dentition.

Spatial and temporal distribution characteristics and influencing factors of tourism eco-efficiency in the Yellow River Basin based on the geographical and temporal weighted regression model.

With economic progression in China, Yellow River Basin serves as a critical economic belt, which has also been recognized as a cradle of Chinese culture. A watershed is a complex structure of social, economic, and natural factors, and the diversity of its components determines its complexity. Studies on the spatiotemporal distribution characteristics and factors influencing the tourism eco-efficiency at the watershed scale are crucial for the sustainable regional socio-economic development, maintaining a virtuous cycle of various ecosystems, and comprehensively considering the utilization and coordinated development of various elements. Based on tourism eco-efficiency, the coordination degree of regional human-land system and the sustainable development levels can be accurately measured. With the tourism eco-efficiency in the Yellow River Basin from 2009 to 2019, the present study considers 63 cities in the Yellow River Basin as the research area by adopting the super-efficiency slacks-based measure (Super-SBM) model. Methods such as trend surface analysis, spatial autocorrelation analysis, elliptic standard deviation analysis, and hot spot analysis were used to explore their spatiotemporal distribution and evolution characteristics. The geographical and temporal weighted regression (GTWR) model was used to determine the factors influencing the tourism eco-efficiency value. The findings are as follows: ①The level of tourism eco-efficiency in the Yellow River Basin is not high, exhibiting a fluctuating upward trend. ②The tourism eco-efficiency in the Yellow River Basin shows significant spatial interdependence and agglomeration. Furthermore, the track of the center of gravity moves from northeast to southwest. ③ The tourism eco-efficiency in the Yellow River Basin is affected by various factors, with the economic development level having the greatest influence.

Relationship Between Sleep Duration and Cognitive Function in Older Adults: Analysis of NHANES and UK Biobank GWAS Data.

OBJECTIVES: To explore the relationship between sleep duration and cognitive functions in older adults using NHANES, a national US population study dataset, and to explore the causal association with Mendelian randomization (MR) using the UK Biobank. METHODS: First, an observational study was conducted with the NHANES database with participants ≥60 years. Sleep duration was measured with accelerometers for 7 consecutive days. Participants were divided into habitual short sleep (<7 h) and long sleep (>9 h) groups. Cognitive functions were measured with the CERAD Word Learning sub-set, Animal Fluency, and Digit Symbol Substitution test (DSST). Multivariate regression models were used to explore relationships between sleep duration and cognitive functions. Second, bidirectional MR was conducted with data for self-reported sleep duration, which came from a genome-wide association study (GWAS) comprising 446,118 adults from the UK Biobank, and general cognitive performance, which was obtained from a recent GWAS study (N = 257,841). Inverse-variance weighted (IVW) was used as the primary estimation of the outcome. RESULTS: In the observational study, 2687 participants were included. Sleep duration was associated with cognitive functions in a non-linear way. Habitual long sleep (>9°h) was associated with lower scores on DSST (OR = 0.01, p = .003) in the fully-adjusted model. The association between habitual short sleep and cognitive functions was insignificant. For the MR, genetically predicted lower general cognitive performance was causally associated with a higher prevalence of habitual short sleep (OR = 0.97, p = 5.1 × 10-7) and long sleep (OR = 0.97, p = 8.87 × 10-16). DISCUSSION: Short and long sleep duration might be both causally associated with worse outcomes of cognitive functions in older adults, highlighting the importance of maintaining sleep health.

Isolation, structure modification, and anti-rheumatoid arthritis activity of isopimarane-type diterpenoids from Orthosiphon aristatus.

Orthosiphon aristatus is a well-known folkloric medicine and herb for Guangdong soup for the treatment of rheumatism in China. Eight isopimarane-type and migrated pimarane-type diterpenoids (1-8), including a new one with a rarely occurring α,ß-unsaturated diketone C-ring, were isolated from O. aristatus. Their structures were determined by spectroscopic methods and quantum chemical calculations. Furthermore, the most abundant compound, orthosiphol K, was structurally modified by modern synthetic techniques to give seven new derivatives (9-15). The anti-rheumatoid arthritis activity of these diterpenoids were evaluated on a TNF-α induced MH7A human rheumatoid fibroblast-like synoviocyte model. Compound 10 showed the most potent activity among these compounds. Based on their inhibitory effects on the release levels of IL-1ß, the preliminary structure-activity relationships were concluded. Furthermore, western blot analysis revealed that 10 could increase the expression of IκBα and decrease the expression of NF-κB p65, and the expression levels of COX-2 and NLRP3 proteins were consequently down-regulated.

Pediatric Hepatoblastoma After Neoadjuvant Chemotherapy: Diagnostic Performance of MR in Staging POSTTEXT and Vascular Involvement.

BACKGROUND: The assessment of resectability after neoadjuvant chemotherapy of hepatoblastoma is dependent on Post-Treatment EXTENT of Disease (POSTTEXT) staging and its annotation factors P (portal venous involvement) and V (hepatic venous/inferior vena cava [IVC] involvement), but MR performance in assessing them remains unclear. PURPOSE: To assess the diagnostic performance of contrast-enhanced MR imaging for preoperative POSTTEXT staging and diagnosing vascular involvement in terms of annotation factors P and V in pediatric hepatoblastoma following neoadjuvant chemotherapy. STUDY TYPE: Retrospective. SUBJECTS: Thirty-five consecutive patients (17 males, median age, 24 months; age range, 6-98 months) with proven hepatoblastoma underwent preoperative MR imaging following neoadjuvant chemotherapy. FIELD STRENGTH/SEQUENCE: 3.0 T; T2-weighted imaging (T2WI), T2WI with fat suppression, diffusion weighted imaging, radial stack-of-the-star/Cartesian 3D Dixon T1-weighted gradient echo imaging. ASSESSMENT: Three radiologists independently assessed the POSTTEXT stages and annotation factors P and V based on the 2017 PRE/POSTTEXT system. The sensitivities and specificities were calculated for 1) diagnosing each POSTTEXT stage; 2) discrimination of stages III and IV (advanced) from those stages I and II (non-advanced) hepatoblastomas; and 3) annotation factors P and V. The combination of pathologic findings and surgical records served as the reference standard. STATISTICAL TESTS: Sensitivity, specificity, Fleiss kappa test. RESULTS: The sensitivity and specificity ranges for discriminating advanced from non-advanced hepatoblastomas were 73.3%-80.0% and 80.0%-90.0%, respectively. For annotation factor P, they were 66.7%-100.0% and 90.6%, respectively. For factor V, they were 75.0% and 67.7%-83.9%, respectively. There was excellent, substantial, and moderate agreement on POSTTEXT staging (Fleiss kappa = 0.82), factors P (Fleiss kappa = 0.64), and factors V (Fleiss kappa = 0.60), respectively. DATA CONCLUSION: MR POSTTEXT provides reliable discrimination between advanced and non-advanced tumors, and MR has moderate to excellent specificity at identifying portal venous and hepatic venous/IVC involvement. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Metabolic engineering of commensal bacteria for gut butyrate delivery and dissection of host-microbe interaction.

An overwhelming number of studies have reported the correlation of decreased abundance of butyrate-producing commensals with a wide range of diseases. However, the molecular-level mechanisms whereby gut butyrate causally affects the host mucosal immunity and pathogenesis were poorly understood, hindered by the lack of efficient tools to control intestinal butyrate. Here we engineered a facultative anaerobic commensal bacterium to delivery butyrate at the intestinal mucosal surface, and implemented it to dissect the causal role of gut butyrate in regulating host intestinal homeostasis in a model of murine chronic colitis. Mechanistically, we show that gut butyrate protected against colitis and preserved intestinal mucosal homeostasis through its inhibiting effect on the key pyroptosis executioner gasdermin D (GSDMD) of colonic epithelium, via functioning as an HDAC3 inhibitor. Overall, our work presents a new avenue to build synthetic living delivery bacteria to decode causal molecules at the host-microbe interface with molecular-level insights.

Rare diphenylheptanoid-phenylheptanoid hybrids with α-glucosidase inhibitory effects from the pollen of Typha angustifolia.

Two rarely occurring diphenylheptanoid-phenylheptanoid hybrid dimers (1 and 2) and one new oxygenated fatty acid (3), as well as two known fatty acid analogues (4 and 5), were isolated from the 70% EtOH extract of the pollen of Typha angustifolia. Their planar structures were established by interpretation of MS and NMR spectroscopic data, and the absolute configurations of 1 and 2 were determined by Mosher's method and quantum chemical TD-DFT calculations of ECD spectra. An in vitro anti-diabetic evaluation of these isolates revealed that compounds 1 and 2 exhibited promising inhibitory activity against α-glucosidase with IC50 values of 11.85 ± 0.69 and 17.06 ± 3.08 µM, respectively. It is the first report on both diphenylheptanoid constituents and α-glucosidase inhibitors from the title plant, which represents a significant phytochemical progress of this herbal species and may serve as a reference for its future medicinal applications.

Semantic Retrieval of Remote Sensing Images Based on the Bag-of-Words Association Mapping Method.

With the increasing demand for remote sensing image applications, extracting the required images from a huge set of remote sensing images has become a hot topic. The previous retrieval methods cannot guarantee the efficiency, accuracy, and interpretability in the retrieval process. Therefore, we propose a bag-of-words association mapping method that can explain the semantic derivation process of remote sensing images. The method constructs associations between low-level features and high-level semantics through visual feature word packets. An improved FP-Growth method is proposed to achieve the construction of strong association rules to semantics. A feedback mechanism is established to improve the accuracy of subsequent retrievals by reducing the semantic probability of incorrect retrieval results. The public datasets AID and NWPU-RESISC45 were used to validate these experiments. The experimental results show that the average accuracies of the two datasets reach 87.5% and 90.8%, which are 22.5% and 20.3% higher than VGG16, and 17.6% and 15.6% higher than ResNet18, respectively. The experimental results were able to validate the effectiveness of our proposed method.

Total Synthesis of Illisimonin†A and Merrilactone†A.

Illicium sesquiterpenes are a large family of biologically active secondary metabolites isolated from Illicium species of plants and are well-known for their activity of neurite outgrowth in cultured neurons. Herein, we propose a comprehensive biosynthetic pathway for illicium sesquiterpenes and report a synthetic route to illisimonin A and merrilactone A based on it. We think that the carbon scaffolds of most of the illicium sesquiterpenes could be synthesized from a dicarbonyl derivative of allo-cedrane through retro-Dieckmann condensation, oxidative cleavage and aldol reaction at suitable oxidation states in Nature. The common intermediate for illisimonin A and merrilactone A similar to the dicarbonyl derivative of allo-cedrane was assembled with up to 82 % ee by an asymmetric intramolecular desymmetrizing reductive Heck reaction by the use of a new type of chiral phosphine ligand. The syntheses of illisimonin A and merrilactone A supported the key transformations of the proposed biosynthetic pathway.

Nerve trunk healing and neuroma formation after nerve transection injury.

The nerve trunk healing process of a transected peripheral nerve trunk is composed of angiogenesis, nerve fiber regeneration, and scarring. Nerve trunk healing and neuroma formation probably share identical molecular mediators and similar regulations. At the nerve transection site, angiogenesis is sufficient and necessary for nerve fiber regeneration. Angiogenesis and nerve fiber regeneration reveal a positive correlation in the early time. Scarring and nerve fiber regeneration show a negative correlation in the late phase. We hypothesize that anti-angiogenesis suppresses neuromas. Subsequently, we provide potential protocols to test our hypothesis. Finally, we recommend employing anti-angiogenic small-molecule protein kinase inhibitors to investigate nerve transection injuries.

Photothermal Treatment of Polydopamine Nanoparticles@Hyaluronic Acid Methacryloyl Hydrogel Against Peripheral Nerve Adhesion in a Rat Model of Sciatic Nerve.

Purpose: Peripheral nerve adhesion occurs following injury and surgery. Functional impairment leading by peripheral nerve adhesion remains challenging for surgeons. Local tissue overexpression of heat shock protein (HSP) 72 can reduce the occurrence of adhesion. This study aims to develop a photothermal material polydopamine nanoparticles@Hyaluronic acid methacryloyl hydrogel (PDA NPs@HAMA) and evaluate their efficacy for preventing peripheral nerve adhesion in a rat sciatic nerve adhesion model. Materials and Methods: PDA NPs@HAMA was prepared and characterized. The safety of PDA NPs@HAMA was evaluated. Seventy-two rats were randomly assigned to one of the following four groups: the control group; the hyaluronic acid (HA) group; the polydopamine nanoparticles (PDA) group and the PDA NPs@HAMA group (n = 18 per group). Six weeks after surgery, the scar formation was evaluated by adhesion scores and biomechanical and histological examinations. Nerve function was assessed with electrophysiological examination, sensorimotor analysis and gastrocnemius muscle weight measurements. Results: There were significant differences in the score on nerve adhesion between the groups (p < 0.001). Multiple comparisons indicated that the score was significantly lower in the PDA NPs@HAMA group (95% CI: 0.83, 1.42) compared with the control group (95% CI: 1.86, 2.64; p = 0.001). Motor nerve conduction velocity and muscle compound potential of the PDA NPs@HAMA group were higher than the control group's. According to immunohistochemical analysis, the PDA NPs@HAMA group expressed more HSP72, less α-smooth muscle actin (α-SMA), and had fewer inflammatory reactions than the control group. Conclusion: In this study, a new type of photo-cured material with a photothermic effect was designed and synthesized-PDA NPs@HAMA. The photothermic effect of PDA NPs@HAMA protected the nerve from adhesion to preserve the nerve function in the rat sciatic nerve adhesion model. This effectively prevented adhesion-related damage.

Deuteration Degree-Controllable Methylation via a Cascade Assembly Strategy using Methylamine-Water as Methyl Source.

We present a novel and effective photocatalytic method for the methylation of ß-diketones with controllable degrees of deuterium incorporation via development of new methyl sources. By utilizing a methylamine-water system as the methyl precursor and a cascade assembly strategy for deuteration degree control, we synthesized methylated compounds with varying degrees of deuterium incorporation, showcasing the versatility of this approach. We examined a range of ß-diketone substrates and synthesized key intermediates for drug and bioactive compounds with varying degrees of deuterium incorporation, ranging from 0 to 3. We also investigated and discussed the postulated reaction pathway. This work demonstrates the utility of readily available reagents, methylamines and water, as a new methyl source, and provides a simple and efficient strategy for the synthesis of degree-controllable deuterium-labelled compounds.

Polydopamine Nanoparticles-Based Photothermal Effect Against Adhesion Formation in a Rat Model of Achilles Tendon Laceration Repair.

Background: Adhesion formation after tendon surgery is a major obstacle to repair of tendon ruptures, and there is still no effective clinical anti-adhesion method. Myofibroblasts expressing α-smooth muscle actin (α-SMA) play a crucial role in adhered fibrous tissue. Heat shock protein (Hsp) 72 can selectively prevent the activation of c-Jun N-terminal kinase (JNK), which mediates the conversion from fibroblasts to myofibroblasts. The purpose of this study was to investigate for the first time whether polydopamine nanoparticles (PDA NPs)-based photothermal effect would attenuate adhesion formation in a rat model of Achilles tendon laceration repair. Materials and Methods: Forty-five adult male Sprague-Dawley rats were randomly assigned to the photothermal group, the control group and the PDA NPs group (n = 15 per group). The primary outcome measure was the adhesion scores at two weeks after surgery according to the grading of Tang et al. The secondary outcomes included the expressions of Hsp 72, JNK, phosphorylated JNK and α-SMA, which were measured by immunohistochemistry or Western blot. Results: The average adhesion score was significantly lower in the photothermal group (4.25 ± 0.21) than that in the control group (5.29 ± 0.12) (p = 0.005) and the PDA NPs group (5.29 ± 0.20) (p = 0.005). Relative to the control group and PDA NPs group, Hsp 72 in the photothermal group was significantly increased whereas α-SMA and p-JNK was significantly decreased, but JNK was not found to be different across the three groups. Conclusion: The photothermal effect produced by PDA NPs could reduce tendon adhesion formation in rats by inhibiting myocyte fibrosis, which may have potential in developing endogenous heating for postsurgical tissue adhesions.

Age-related hypertrophy of adenoid and tonsil with its relationship with craniofacial morphology.

BACKGROUND: When analyzing the relationship between adenotonsillar hypertrophy and craniofacial morphology, researchers generally regarded hypertrophied adenoids and tonsils as a whole. It remains unclear whether different enlarged sites of pharyngeal lymphoid tissue would correlate with multiple craniofacial subtypes. We hypothesized there would be craniofacial subtypes correlated with different locations of hypertrophied adenoid and tonsil. METHODS: Lateral cephalometric radiographs were obtained from 466 children (171 boys and 295 girls, aged 12.27 ± 2.69 years). They were divided into four groups according to different sites of enlarged pharyngeal lymphoid tissue: adenoid hypertrophy group (AG, n = 126), tonsillar hypertrophy group (TG, n = 59), adenotonsillar hypertrophy group (ATG, n = 69) and control group (CG, n = 212). Five commonly used angles for cephalometric measurements were investigated: SNA (Sella-Nasion-Point A), SNB (Sella-Nasion-Point B), ANB (Point A-Nasion-Point B), mandibular plane angle (MP/SN) and Y-axis angle (SGn/FH). RESULTS: Children with isolated tonsillar hypertrophy correlated with increased SNA (unstandardized regression coefficient B = 1.38, p = 0.009) and SNB (B = 1.99, p = 0.001) compared with controls. However, children with isolated adenoid hypertrophy correlated with decreased SNB (B=-0.94, p = 0.036), increased ANB (B = 0.74, p = 0.014) and increased MP/SN (B = 2.22, p < 0.001). Similarly, children with adenotonsillar hypertrophy correlated with decreased SNB (B=-1.36, p = 0.015), increased ANB (B = 1.35, p < 0.001) and increased MP/SN (B = 2.64, p = 0.001). CONCLUSIONS: Isolated adenoid hypertrophy correlated with a retrognathic mandible, an increased maxillo-mandibular sagittal discrepancy, and an increased mandibular plane angle. Isolated tonsillar hypertrophy correlated with maxillary and mandibular protrusion. Adenotonsillar hypertrophy did not show a superimposed craniofacial pattern of the above two but showed the same craniofacial pattern as isolated adenoid hypertrophy.

Social incentives foster cooperation through guilt aversion: An effect that diminishes with primary psychopathic traits.

The association between primary psychopathic traits and non-cooperative behaviors is well-identified. There is a lack of studies on how to motivate cooperative behaviors in individuals with primary psychopathic traits. This study investigated the effects of monetary incentives and social incentives on promoting cooperation in healthy adults with varying primary psychopathic traits. Participants played a one-shot public goods game (PGG) with other anonymous players in three different contexts: a social incentives context where participants' decisions would be judged by others, a monetary incentives context where participants' decisions would result in winning or losing money depending on their contributions, and a control condition where no additional incentives were implemented. We found that, compared to the control condition, both monetary and social incentives significantly improved participants' contributions to the public project-an indicator of cooperative behavior. However, the association between higher primary psychopathic traits and less cooperation was only observed in the context of social incentives. Computational modeling further revealed that this effect can be explained by the diminishing guilt aversion when participants deliberately violated their inferred expectations of themselves from others' perspectives. This study found that social incentives can encourage cooperative behaviors in non-clinical psychopathy, and identified the mental processes navigating this effect.

Anatomical phenotype of obstructive sleep apnea patients based on cluster analysis.

OBJECTIVES: To generate a novel subtype of obstructive sleep apnea (OSA) based on anatomical features and verify the differences in the response of different subtypes to orthodontic treatment, thus providing a theoretical reference for clinical decision-making. MATERIALS AND METHODS: A K-means cluster analysis was performed for this retrospective serial study, which includes 722 OSA patients, aged 44.0 (36.0, 54.0) years, 80.2% male, with apnea-hypopnea index (AHI) of 23.2 (13.4, 39.6) events·h-1 , and body mass index (BMI) of 25.47 ± 3.00 kg·m-2 . All samples were divided into three subtypes based on AHI, BMI, and five variables of craniofacial measurements. Sixty-seven cases with mandibular advancement devices (MAD) therapeutic results were further applied to validate the efficacy and side effects of this treatment in different subtypes. RESULTS: Two hundred and thirty patients (31.9%) were characterized as cluster 1: AHI of 17.65 (11.80, 30.42) events·h-1 , BMI of 23.65 ± 2.62 kg·m-2 , with skeletal Class II high-angle shape. Cluster 2 included 278 patients (38.5%): AHI of 17.00 (11.00, 26.48) events·h-1 , BMI of 25.36 ± 2.53 kg·m-2 , soft palate length (SPL) of 39.25 mm (36.12, 42.20), with basically normal skeleton and normal airway size. Cluster 3, consisting of 214 patients (29.6%), exhibited a combination of anatomical deformity and obesity, with the highest AHI and BMI of 45.35 (30.42, 62.53) events·h-1 and 27.57 ± 2.59 kg·m-2 respectively, but less deformity degree than cluster 1. Cluster 2 had the highest response rate and relatively mild side effects with MAD. CONCLUSIONS: Orthodontic treatment based on anatomical morphology could exert a better effect on mild-moderate OSA patients with mild skeletal deformity.

Tricrilactones A-H, Potent Antiosteoporosis Macrolides with Distinctive Ring Skeletons from Trichocladium crispatum, an Alpine Moss-Associated Fungus.

Tricrilactones A-H (1-8), a new family of oligomeric 10-membered macrolides featuring collectively five unique ring skeletons, were isolated from a hitherto unexplored fungus, Trichocladium crispatum. Compounds 1 and 7 contain two unconventional bridged (aza)tricyclic core skeletons, 2, 3, 5, and 6 share an undescribed tetracyclic 9/5/6/6 ring system, 4 bears an uncommon 9/5/6/10/3-fused pentacyclic architecture, and 8 is a dimer bridged by an unexpected C-C linkage. Their structures, including absolute configurations, were elucidated by spectroscopic analysis, quantum chemical calculations, and X-ray diffraction analysis. Importantly, the absolute configuration of the highly flexible side chain of 1 was resolved by the asymmetric synthesis of its four stereoisomers. The intermediate-trapping and isotope labeling experiments facilitated the proposal of the biosynthetic pathway for these macrolides. In addition, their antiosteoporosis effects were evaluated in vivo (zebrafish).

Acute liver injury induced by carbon tetrachloride reversal by Gandankang aqueous extracts through nuclear factor erythroid 2-related factor 2 signaling pathway.

The aims of this study were to evaluated the effect and underlying mechanism of Gandankang (GDK) aqueous extract in alleviating the acute liver injury induced by carbon tetrachloride (CCl4) in vivo and in vitro. Mice were divided into 5 groups (n = 8) for acute (Groups: control, 0.3 % CCl4, BD (Bifendate), 1.17, 2.34 and 4.68 mg/kg GDK) liver injury study. 10 µL/g CCl4 with corn oil were injected interperitoneally (i.p) expect the control group. HepG2 cells were used in vitro study. The results showed GDK can effectively inhibit liver damage and restore the structure and function of the liver. In mechanism, GDK inhibited CCl4-induced liver fibrosis and blocked the NF-κB pathway to effectively inhibit the hepatic inflammatory response; and inhibited CCl4-induced oxidative stress by upregulating the Keap1/Nrf2 pathway-related proteins and promoting the synthesis of several antioxidants. Additionally, it inhibited ferroptosis in the liver by regulating the expression of ACSl4 and GPX4. GDK reduced lipid peroxide generation in vitro by downregulating the production of reactive oxygen species and Fe2+ aggregation, thereby inhibiting ferroptosis and alleviating CCl4-induced hepatocyte injury. In conclusion, we describe the potential complex mechanism underlying the effect of GDK against acute liver injury.

Combined Verapamil-Polydopamine Nanoformulation Inhibits Adhesion Formation in Achilles Tendon Injury Using Rat Model.

Introduction: Topical verapamil has been demonstrated to reduce the fibroproliferative scar. Therefore, it was hypothesized that topical verapamil could reduce adhesion formation after tendon repair. The current study aimed to examine the effects of verapamil-loaded polydopamine nanoparticles (VP-PDA NPs) on the adhesion formation of Achilles tendon laceration and repair in a rat model. Methods: We randomly assigned 72 male Sprague-Dawley rats to the control, the PDA NPs, and the VP-PDA NPs groups (n = 24 per group). The quality of tendon healing was evaluated by the maximal tensile strength four and six weeks after surgery. The degree of tendon adhesion was scored on days 4, 15, 29, and 43 after surgery. The expressions of transforming growth factor-beta 1 (TGF-ß1), vimentin, α-smooth muscle actin (α-SMA), and collagens type I and III were detected through Western blotting or immunohistochemistry at four weeks after surgery. Results: In vitro release tests revealed that 61.3% of verapamil was released from VP-PDA NPs in four weeks. There was a significant increase in average failure to load in the VP-PDA NPs group (89.27 ± 5.09 N) compared with the PDA NPs group (65.52 ± 2.04 N) (p = 0.003) and the control group (74.52 ± 4.24 N) (p = 0.029). Adhesion scores were significantly reduced in the VP-PDA NPs group at six weeks (3.175 ± 0.08) and four weeks (3.35 ± 0.25) compared with the other groups. Moreover, VP-PDA NPs significantly reduced the expression of vimentin, α-SMA, TGF-ß1, and collagens type I and III. Conclusion: These data suggest that VP-PDA NPs reduced adhesion formation and enhanced tendon healing during rat tendon injury. Since topical verapamil has been used in clinics without side effects, VP-PDA NPs would have direct translation implications. However, its anti-adhesive effects on intrasynovial tendon injury must be examined.