Furazolidone reduces the pathogenesis of Trueperella pyogenes and Pseudomonas aeruginosa co-infection in a mouse model.

The prevalence of abscess disease significantly limits the population expansion of captive forest musk deer, which is an endangered species protected by the legislation of China. Our prior work had demonstrated that Trueperella pyogenes and Pseudomonas aeruginosa are two important microorganisms in causing the abscess disease of forest musk deer, and furazolidone could inhibit the growth and virulence of the pathogens in vitro. In this study, the in vivo protection activity of furazolidone was evaluated by using mouse models chronically infected with T. pyogenes and P. aeruginosa. The results showed that furazolidone treatment significantly increased the survival rates of mice in the co-infection group, all the mice survived at 14 days post-infection. The damage degree of the lung tissues caused by bacterial infection was ameliorated by the treatment of furazolidone from 7 to 14 days post-infection, which also reduced the residual bacterial burden in the lungs. Compared to the untreated control group, the expression levels of genes activated by the quorum-sensing system of P. aeruginosa and the core virulence regulatory genes of T. pyogenes were significantly suppressed by furazolidone. In addition, the results of transcriptomic analyses showed that 270 DEGs were identified in the co-infection group. This finding further revealed that the immune responses of mice could be enhanced by the treatment of furazolidone, and this might also contribute to the clearance of bacteria from the lungs. Therefore, this study clearly reveals the protection activity of furazolidone against P. aeruginosa and T. pyogenes infection, and thus provides a promising candidate in the treatment of abscess disease.

Clinical, myopathological, and genetic features of two Chinese families with Andersen-Tawil syndrome.

Purpose: To explore the clinical, muscle pathological, and pathogenic gene mutation characteristics of Andersen-Tawil Syndrome (ATS) and enhance the understanding of ATS among clinical practitioners. Methods: Retrospective analysis of clinical data and muscle pathology of two ATS families, along with genetic testing for probands and some family members. Results: In Family 1, spanning four generations, four individuals were affected, while Family 2 had two affected individuals across four generations. All six patients in both families experienced onset in childhood, presenting with periodic paralysis, arrhythmias, and craniofacial skeletal abnormalities. In Family 1, the proband's periodic paralysis was more triggered by low temperature and exercise, occurring several times a year, lasting 4-7 days. All three adult patients in Family 1 had a history of hypokalemia, and the frequency and severity of attacks were reduced after regular oral potassium supplement therapy. Two adult females in Family 1 experienced limb weakness triggered by stress, exertion, and premenstrual period, with milder symptoms than the proband. In Family 2, the proband's periodic paralysis typically occurred the day after excessive exertion, with a frequency of approximately 2-3 months. Two years prior, the proband developed arrhythmias without palpitations or chest tightness. The proband's brother experienced intermittent limb weakness during adolescence, remained untreated, and had sudden death at age 40. Physical examination revealed characteristic features in Family 1 and both probands: small mandible, wide eye spacing, and fifth-digit clinodactyly. Four adult patients were shorter in stature, while the growth status of a pediatric patient was indeterminate. Supplementary tests showed a history of hypokalemia during muscle weakness episodes in Family 1, while Family 2 patients had normal potassium levels during episodes. The long exercise tests were positive in both probands. Muscle MRI showed no significant abnormalities, but muscle pathology revealed rimmed vacuoles and tubular aggregates. Genetic testing identified KCNJ2 gene mutations in two probands and some of their family members, with c.407C > T (p.S136F) heterozygous mutation in Family 1 and c.652C > T (p.R218W) heterozygous mutation in Family 2. Conclusion: Among the clinical symptoms of the patients with Andersen-Tawil Syndrome in this study, not everyone exhibits the full triad of signs: periodic paralysis is the most common initial symptom, craniofacial and digit skeletal abnormalities are characteristic signs, and ventricular arrhythmias pose the most serious potential risk. Given that these typical symptoms were observed in 5 out of 6 patients, clinicians should pay special attention to these typical symptoms, and patients with these symptoms should be followed up over time. Muscle biopsy May reveal pathological changes such as tubular aggregates, but genetic testing for KCNJ gene mutations remains a crucial diagnostic criterion for this syndrome.

Surface Property Regulation of a Magnetron-Sputtered NiOx Hole Transport Layer for High-Performance Inverted Perovskite Solar Cells.

The inverted perovskite solar cells (PSCs) are gaining increasing attention recently for their unprecedented advantages, such as better integration with tandem and flexible designs, negligible hysteresis, good operational stability, and compatibility with commercially scalable fabrication approaches. Nickel oxide (NiOx) films prepared by magnetron sputtering technology exhibit excellent scalability and reproducibility, which could well meet the requirements of the large-scale production of inverted PSCs. However, NiOx prepared by vacuum methods generally has fewer surface hydroxyl groups, deteriorating the wettability and damaging the interface contact with the perovskite. Particularly, the Ni3+ defects on the NiOx surface could lead to unfavorable redox reactions with organic cations in the perovskite under high temperatures, promoting the rapid degradation of the perovskite. Thus, surface regulation of sputtered NiOx is imperative for high-performance PSCs. Herein, 4-(trifluoromethyl) phenylcarbamate hydrochloride (TFFA) was used to regulate the surface properties of sputtered NiOx. The strongly electronegative F ions in TFFA passivated the Ni3+ defects on the NiOx surface, suppressed unfavorable interface reactions, and improved charge recombination. The polar ammonium functional group was used to adjust the surface energy of NiOx, thereby improving the wettability and optimizing the crystallization kinetics of the perovskite. As a result, the power conversion efficiency (PCE) of PSCs reached 22.76%, which was among the highest PCEs reported for sputtered NiOx-based inverted PSCs to date. Moreover, the unencapsulated target devices exhibited better stability, maintaining over 85% of the initial PCE after aging for approximately 1200 h in a N2 environment. Our achievements pointed out a practical strategy for enhancing the performance of sputtered NiOx-based inverted PSCs, which could potentially accelerate the development and application of large-area PSCs.

cRGD-platelet@MnO/MSN@PPARα/LXRα Nanoparticles Improve Atherosclerosis in Rats by Inhibiting Inflammation and Reducing Blood Lipid.

OBJECTIVE: Atherosclerosis (AS) is an inflammatory disease of arterial intima driven by lipids. Liver X receptor alpha (LXRα) and peroxisome proliferator-activated receptor alpha (PPARα) agonists are limited in the treatment of AS due to their off-target effects and serious side effects. Therefore, this study was designed to construct a novel nanoparticle (NP) and evaluate its mechanism of action on inflammation inhibition and lipid reduction in AS. METHODS: We synthesized cRGD-platelet@MnO/MSN@PPARα/LXRα NPs (cRGD-platelet- NPs) and confirmed their size, safety, and targeting ability through various tests, including dynamic light scattering and immunofluorescence. In vivo and in vitro experiments assessed cell proliferation, apoptosis, inflammation, and plaque formation. Finally, the NF-κB signaling pathway expression in rat aorta was determined using a western blot. RESULTS: The synthesis of cRGD-platelet-NPs was successful; the particle size was approximately 150 nm, and the PDI was below 0.3. They could be successfully absorbed by cells, exhibiting high safety in vivo and in vitro. The cRGD-platelet-NPs successfully reduced plaque formation, improved lipid profiles by lowering LDL-cholesterol, total cholesterol, and triglycerides, and raised HDL-cholesterol levels. Additionally, they decreased inflammatory markers in the serum and aortic tissue, suggesting reduced inflammation. Immunohistochemistry and western blot analyses indicated that these NPs could not only promote M2 macrophage polarization but also suppress the NF-κB signaling pathway. CONCLUSION: The newly developed cRGD-platelet-NPs with high safety are a promising approach to AS treatment, which can regulate ABCA1, reduce the formation of AS plaques, and enhance cholesterol efflux. The mechanism may involve the suppression of the NF-κB signaling pathway.

Identification and molecular mechanism of novel hypoglycemic peptide in ripened pu-erh tea: Molecular docking, dynamic simulation, and cell experiments.

Ripened pu-erh tea is known to have beneficial hypoglycemic properties. However, it remains unclear whether the bioactive peptides produced during fermentation are also related to hypoglycemic potential. This study aimed to identify hypoglycemic peptides in ripened pu-erh tea and to elucidate their bioactive mechanisms using physicochemical property prediction, molecular docking, molecular dynamics simulations, and cell experiments. Thirteen peptides were identified by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Among them, AADTDYRFS (AS-9) and AGDGTPYVR (AR-9) exhibited high α-glucosidase inhibitory activity, with half-maximal inhibitory concentration (IC50) values of 0.820 and 3.942 mg/mL, respectively. Molecular docking and dynamics simulations revealed that hydrogen bonding, hydrophobic interactions, and van der Waals forces assist peptides AS-9 and AR-9 in forming stable and tight complexes with α-glucosidase. An insulin-resistance (IR)-HepG2 cell model was established. AS-9 was non-toxic to IR-HepG2 cells and significantly increased the glucose consumption capacity, hexokinase, and pyruvate kinase activities of IR-HepG2 cells (p < 0.05). AS-9 alleviated glucose metabolism disorders and ameliorated IR by activating the IRS-1/PI3K/Akt signaling pathway and increasing the expression levels of MDM2, IRS-1, Akt, PI3K, GLUT4, and GSK3ß genes. In addition, no hemolysis of mice red blood cells red blood cells occurred at concentrations below 1 mg/mL. This work first explored hypoglycemic peptides in ripened pu-erh tea, providing novel insights for enhancing its functional value.

PARN Maintains RNA Stability to Regulate Insulin Maturation and GSIS in Pancreatic ß Cells.

Diabetes, a metabolic disorder characterized by hyperglycemia, underscores the importance of normal pancreatic ß-cell development and function in maintaining glucose homeostasis. Poly(A)-specific ribonuclease (PARN) serves as the principal regulator of messenger RNA (mRNA) stability, yet its specific role in pancreatic ß cells remains unclear. This study utilizes mice with targeted PARN deficiency in ß cells to elucidate this role. Notably, Parn conditional knockout mice present unaltered ß-cell development and insulin sensitivity but reduced glucose-stimulated insulin secretion (GSIS). The observed outcomes are corroborated in NIT-1 cells. Furthermore, transcriptomic analyses reveal aberrant mRNA expression of genes crucial for insulin secretion in PARN-deficient ß cells. Insights from linear amplification of complementary DNA ends and sequencing and coimmunoprecipitation experiments reveal an interaction between PARN and polypyrimidine tract-binding protein 1 (PTBP1), regulating the RNA stability of solute carrier family 30, member 8 (Slc30a8) and carbohydrate sulfotransferase 3 (Chst3). Interference with either PARN or PTBP1 disrupts this stability. These data indicate that PARN deficiency hampers GSIS and insulin maturation by destabilizing Slc30a8 and Chst3 RNAs. These findings provide compelling evidence indicating that PARN is a potential therapeutic target for enhancing insulin maturation and secretion.

Dysregulation of mitochondrial dynamics and mitophagy are involved in high-fat diet-induced steroidogenesis inhibition.

Male obesity is a pandemic health issue and can disrupt testicular steroidogenesis. Here, we explored the mechanism by which a high-fat diet (HFD) induced steroidogenic inhibition. As expected, HFD induced lipid droplet accumulation and reduced the expression of StAR, P450scc, and 3ß-HSD, three steroidogenic enzymes, in mouse testes. Palmitic acid (PA), a saturated fatty acid usually used to trigger lipotoxicity in vitro, induced greater accumulation of lipid droplets and the downregulation of steroidogenic enzymes in TM3 cells. Mechanistically, both HFD and PA disturbed mitochondrial fusion/fission dynamics and then induced mitochondrial dysfunction and mitophagy inhibition in mouse Leydig cells. Additionally, mitochondrial fusion promoter M1 attenuated PA-induced imbalance of mitochondrial dynamics, mitophagy inhibition, mitochondrial reactive oxygen species (ROS) production, and mitochondrial dysfunction in TM3 cells. Mitofusin 2 (Mfn2) knock-down further aggravated the PA-induced imbalance of mitochondrial dynamics, mitochondrial ROS production, and mitochondrial dysfunction in TM3 cells. Importantly, M1 rescued PA-induced downregulation of steroidogenic enzymes, whereas Mfn2 knock-down further aggravated PA-induced downregulation of steroidogenic enzymes in TM3 cells. Overall, our results provide laboratory evidence that mitochondrial dysfunction and mitophagy inhibition caused by dysregulation of mitochondrial fusion may be involved in HFD-induced steroidogenesis inhibition in mouse Leydig cells.

Optimization of saponin extraction from the leaves of Panax notoginseng and Panax quinquefolium and evaluation of their antioxidant, antihypertensive, hypoglycemic and anti-inflammatory activities.

Panax notoginseng and Panax quinquefolium are important economic plants that utilize dried roots for medicinal and food dual purposes; there is still insufficient research of their stems and leaves, which also contain triterpenoid saponins. The extraction process was developed with a total saponin content of 12.30 ± 0.34% and 12.19 ± 0.64% for P. notoginseng leaves (PNL) and P. quinquefolium leaves (PQL) extracts, respectively. PNL and PQL saponin extracts showed good antioxidant, antihypertensive, hypoglycemic, and anti-inflammatory properties in vitro and RAW264.7 cells. A total of 699 metabolites were identified in PNL and PQL saponin extracts, with the majority being triterpenoid saponins, flavonoids and amino acids. Fourteen ginsenosides, 18 flavonoids or alkaloids, and 16 amino acids were enriched in both saponin extracts. Overall, the utilization of saponins from medicinal plants PNL and PQL has been developed to facilitate systematic research in the functional food and natural product industries.

Effects of acetylcysteine on micro-inflammation and pulmonary ventilation in chronic obstructive pulmonary disease exacerbation.

BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a serious complication of chronic obstructive pulmonary disease, often characterized by increased morbidity and mortality. In traditional Chinese medicine, AECOPD is linked to phlegm-heat and blood-stasis, presenting symptoms like thick sputum, fever, and chest pain. It has been shown that acetylcysteine inhalation in conjunction with conventional therapy significantly reduced inflammatory markers and improved lung function parameters in patients with AECOPD, suggesting that acetylcysteine may be an important adjunctive therapy for patients with phlegm-heat-blood stasis type AECOPD. AIM: To investigate the effect of acetylcysteine on microinflammation and lung ventilation in patients with phlegm-heat and blood-stasis-type AECOPD. METHODS: One hundred patients with phlegm-heat and blood-stasis-type AECOPD were randomly assigned to two groups. The treatment group received acetylcysteine inhalation (10% solution, 5 mL, twice daily) along with conventional therapy, whereas the control group received only conventional therapy. The treatment duration was 14 d. Inflammatory markers (C-reactive protein, interleukin-6, and tumor necrosis factor-alpha) in the serum and sputum as well as lung function parameters (forced expiratory volume in one second, forced vital capacity, and peak expiratory flow) were assessed pre- and post-treatment. Acetylcysteine inhalation led to significant reductions in inflammatory markers and improvements in lung function parameters compared to those in the control group (P < 0.05). This suggests that acetylcysteine could serve as an effective adjunct therapy for patients with phlegm-heat and blood-stasis-type AECOPD. RESULTS: Acetylcysteine inhalation significantly reduced inflammatory markers in the serum and sputum and improved lung ventilation function parameters in patients with phlegm-heat and blood-stasis type AECOPD compared with the control group. These differences were statistically significant (P < 0.05). The study concluded that acetylcysteine inhalation had a positive effect on microinflammation and lung ventilation function in patients with this type of AECOPD, suggesting its potential as an adjuvant therapy for such cases. CONCLUSION: Acetylcysteine inhalation demonstrated significant improvements in reducing inflammatory markers in the serum and sputum, as well as enhancing lung ventilation function parameters in patients with phlegm-heat and blood-stasis type AECOPD. These findings suggest that acetylcysteine could serve as a valuable adjuvant therapy for individuals with this specific type of AECOPD, offering benefits for managing microinflammation and optimizing lung function.

Acceleration of bone repairation by BMSCs overexpressing NGF combined with NSA and allograft bone scaffolds.

BACKGROUND: Repairation of bone defects remains a major clinical problem. Constructing bone tissue engineering containing growth factors, stem cells, and material scaffolds to repair bone defects has recently become a hot research topic. Nerve growth factor (NGF) can promote osteogenesis of bone marrow mesenchymal stem cells (BMSCs), but the low survival rate of the BMSCs during transplantation remains an unresolved issue. In this study, we investigated the therapeutic effect of BMSCs overexpression of NGF on bone defect by inhibiting pyroptosis. METHODS: The relationship between the low survival rate and pyroptosis of BMSCs overexpressing NGF in localized inflammation of fractures was explored by detecting pyroptosis protein levels. Then, the NGF+/BMSCs-NSA-Sca bone tissue engineering was constructed by seeding BMSCs overexpressing NGF on the allograft bone scaffold and adding the pyroptosis inhibitor necrosulfonamide(NSA). The femoral condylar defect model in the Sprague-Dawley (SD) rat was studied by micro-CT, histological, WB and PCR analyses in vitro and in vivo to evaluate the regenerative effect of bone repair. RESULTS: The pyroptosis that occurs in BMSCs overexpressing NGF is associated with the nerve growth factor receptor (P75NTR) during osteogenic differentiation. Furthermore, NSA can block pyroptosis in BMSCs overexpression NGF. Notably, the analyses using the critical-size femoral condylar defect model indicated that the NGF+/BMSCs-NSA-Sca group inhibited pyroptosis significantly and had higher osteogenesis in defects. CONCLUSION: NGF+/BMSCs-NSA had strong osteogenic properties in repairing bone defects. Moreover, NGF+/BMSCs-NSA-Sca mixture developed in this study opens new horizons for developing novel tissue engineering constructs.

Structure-optimized and microenvironment-inspired nanocomposite biomaterials in bone tissue engineering.

Critical-sized bone defects represent a significant clinical challenge due to their inability to undergo spontaneous regeneration, necessitating graft interventions for effective treatment. The development of tissue-engineered scaffolds and regenerative medicine has made bone tissue engineering a highly viable treatment for bone defects. The physical and biological properties of nanocomposite biomaterials, which have optimized structures and the ability to simulate the regenerative microenvironment of bone, are promising for application in the field of tissue engineering. These biomaterials offer distinct advantages over traditional materials by facilitating cellular adhesion and proliferation, maintaining excellent osteoconductivity and biocompatibility, enabling precise control of degradation rates, and enhancing mechanical properties. Importantly, they can simulate the natural structure of bone tissue, including the specific microenvironment, which is crucial for promoting the repair and regeneration of bone defects. This manuscript provides a comprehensive review of the recent research developments and applications of structure-optimized and microenvironment-inspired nanocomposite biomaterials in bone tissue engineering. This review focuses on the properties and advantages these materials offer for bone repair and tissue regeneration, summarizing the latest progress in the application of nanocomposite biomaterials for bone tissue engineering and highlighting the challenges and future perspectives in the field. Through this analysis, the paper aims to underscore the promising potential of nanocomposite biomaterials in bone tissue engineering, contributing to the informed design and strategic planning of next-generation biomaterials for regenerative medicine.

Unveiling the impact of cryptic plasmids curing on Escherichia coli Nissle 1917: massive increase in Ag43c expression.

Escherichia coli Nissle 1917 (EcN) is an important chassis strain widely used for the development of live biotherapeutic products (LBPs). EcN strain naturally harbors two cryptic plasmids with unknown function. During the development of LBPs using EcN strain, the cryptic plasmids were cured usually to avoid plasmid incompatibility or alleviate metabolic burdens associated with these cryptic plasmids. While the cryptic plasmids curing in EcN may appear to be a routine procedure, the comprehensive impact of cryptic plasmids curing on the EcN strain remains incompletely understood. In the present study, the effects of cryptic plasmids curing on EcN were investigated using transcriptome sequencing. The results revealed that only a small number of genes showed significant changes in mRNA levels after cryptic plasmid curing (4 upregulated and 6 downregulated genes), primarily involved in amino acid metabolism. Furthermore, the flu gene showed the most significant different expression, encoding Antigen 43 (Ag43) protein, a Cah family adhesin. Mass spectrometry analysis further confirmed the significant increase in Ag43 expression. Ag43 is commonly present in Escherichia coli and mediates the bacterial autoaggregation. However, despite the upregulation of Ag43 expression, no Ag43-mediated cell self-sedimentation was observed in the cured EcN strain. These findings contribute to making informed decisions regarding the curing of the cryptic plasmids when Escherichia coli Nissle 1917 is used as the chassis strain.

LncRNA-SERB promotes vasculogenic mimicry (VM) formation and tumor metastasis in renal cell carcinoma.

A growing body of evidence shows that vasculogenic mimicry (VM) is closely related to the invasion and metastasis of many tumor cells. Although the estrogen receptor (ER) can promote initiation and progression of renal cell carcinoma (RCC), how the downstream biomolecules are involved, and the detailed mechanisms of how ER expression is elevated in RCC remain to be further elucidated. Here, we discovered that long noncoding RNA (LncRNA)-SERB is highly expressed in tumor cells of RCC patients. We used multiple RCC cells and an in vivo mouse model for our study, and results indicated that LncRNA-SERB could boost RCC VM formation and cell invasion in vitro and in vivo. Although a previous report showed that ERß can affect the VM formation in RCC, it is unclear which factor could upregulate ERß. This is the first study to show LncRNA-SERB can be the upstream regulator of ERß to control RCC progression. Mechanistically, LncRNA-SERB may increase ERß via binding to the promoter area, and ERß functions through transcriptional regulation of zinc finger E-box binding homeobox 1 (ZEB1) to regulate VM formation. These results suggest that LncRNA-SERB promotes RCC cell VM formation and invasion by upregulating the ERß/ZEB1 axis and that therapeutic targeting of this newly identified pathway may better inhibit RCC progression.

Co-immunization with DNA vaccines encoding yidR and IL-17 augments host immune response against Klebsiella pneumoniae infection in mouse model.

Klebsiella pneumoniae is an important gram-negative bacterium that causes severe respiratory and healthcare-associated infections. Although antibiotic therapy is applied to treat severe infections caused by K. pneumoniae, drug-resistant isolates pose a huge challenge to clinical practices owing to adverse reactions and the mismanagement of antibiotics. Several studies have attempted to develop vaccines against K. pneumoniae, but there are no licensed vaccines available for the control of K. pneumoniae infection. In the current study, we constructed a novel DNA vaccine, pVAX1-YidR, which encodes a highly conserved virulence factor YidR and a recombinant expression plasmid pVAX1-IL-17 encoding Interleukin-17 (IL-17) as a molecular adjuvant. Adaptive immune responses were assessed in immunized mice to compare the immunogenicity of the different vaccine schemes. The results showed that the targeted antigen gene was expressed in HEK293T cells using an immunofluorescence assay. Mice immunized with pVAX1-YidR elicited a high level of antibodies, induced strong cellular immune responses, and protected mice from K. pneumoniae challenge. Notably, co-immunization with pVAX1-YidR and pVAX1-IL-17 significantly augmented host adaptive immune responses and provided better protection against K. pneumoniae infections in vaccinated mice. Our study demonstrates that combined DNA vaccines and molecular adjuvants is a promising strategy to develop efficacious antibacterial vaccines against K. pneumoniae infections.

Tricholoma matsutake polysaccharides suppress excessive melanogenesis via JNK-mediated pathway: Investigation in 8- methoxypsoralen induced B16-F10 melanoma cells and clinical study.

Skin hyperpigmentation is a worldwide condition associated with augmented melanogenesis. However, conventional therapies often entail various adverse effects. Here, we explore the safety range and depigmentary effects of polysaccharides extract of Tricholoma matsutake (PETM) in an in vitro model and further evaluated its efficacy at the clinical level. An induced-melanogenesis model was established by treating B16-F10 melanoma cells with 8-methoxypsoralen (8-MOP). Effects of PETM on cell viability and melanin content were examined and compared to a commonly used depigmentary agent, α-arbutin. Expressions of key melanogenic factors and upstream signaling pathway were analysed by quantitative PCR and western blot. Moreover, a placebo-controlled clinical study involving Chinese females with skin hyperpigmentation was conducted to measure the efficacy of PETM on improving facial pigmented spots, melanin index, and individual typology angle (ITA°). Results demonstrated that PETM (up to 0.5 mg/mL) had little effect on the viability and motility of B16-F10 cells. Notably, it significantly suppressed the melanin content and expressions of key melanogenic factors induced by 8-MOP in B16-F10 melanoma cells. Western blotting results revealed that PETM inhibited melanogenesis by inactivating c-Jun N-terminal kinase (JNK), and this inhibitory role could be rescued by JNK agonist treatment. Clinical findings showed that PETM treatment resulted in a significant reduction of facial hyperpigmented spot, decreased melanin index, and improved ITA° value compared to the placebo-control group. In conclusion, these in vitro and clinical evidence demonstrated the safety and depigmentary efficacy of PETM, a novel polysaccharide agent. The distinct mechanism of action of PETM on melanogenic signaling pathway positions it as a promising agent for developing alternative therapies.

Metal-Organic Frameworks Marry Sponge: New Opportunities for Advanced Water Treatment.

Metal-organic frameworks (MOFs) have garnered attention across various fields due to their noteworthy features like high specific surface area, substantial porosity, and adjustable performance. In the realm of water treatment, MOFs exhibit great potential for eliminating pollutants such as organics, heavy metals, and oils. Nonetheless, the inherent powder characteristics of MOFs pose challenges in terms of recycling, pipeline blockage, and even secondary pollution in practical applications. Addressing these issues, the incorporation of MOFs into sponges proves to be an effective solution. Strategies like one-pot synthesis, in situ growth, and impregnation are commonly employed for loading MOFs onto sponges. This review comprehensively explores the synthesis strategies of MOFs and sponges, along with their applications in water treatment, aiming to contribute to the ongoing advancement of MOF materials.

Rhizoma Paridis saponins attenuate Gram-negative bacteria-induced inflammatory acne by binding to KEAP1 and modulating Nrf2 and MAPK pathways.

Acne vulgaris represents a chronic inflammatory condition, the pathogenesis of which is closely associated with the altered skin microbiome. Recent studies have implicated a profound role of Gram-negative bacteria in acne development, but there is a lack of antiacne agents targeting these bacteria. Polyphyllins are major components of Rhizoma Paridis with great anti-inflammatory potential. In this study, we aimed to evaluate the antiacne effects and the underlying mechanisms of PPH and a PPH-enriched Rhizoma Paridis extract (RPE) in treating the Gram-negative bacteria-induced acne. PPH and RPE treatments significantly suppressed the mRNA and protein expressions of interleukin (IL)-1ß and IL-6 in lipopolysaccharide (LPS)-induced RAW 264.7 and HaCaT cells, along with the intracellular reactive oxygen species (ROS) generation. Furthermore, PPH and RPE inhibited the nuclear translocation of nuclear factor kappa-B (NF-κB) P65 in LPS-induced RAW 264.7 cells. Based on molecular docking, PPH could bind to kelch-like ECH-associated protein 1 (KEAP1) protein. PPH and RPE treatments could activate nuclear factor erythroid 2-related factor 2 (NRF2) and upregulate haem oxygenase-1 (HO-1). Moreover, RPE suppressed the mitogen-activated protein kinase (MAPK) pathway. Therefore, PPH-enriched RPE showed anti-inflammatory and antioxidative effects in vitro, which is promising for alternative antiacne therapeutic.

Value of multiplanar reconstruction in multi-slice computed tomography for the detection of foreign body in the pulmonary artery: a case report.

Multi-slice computed tomography (MSCT) is the primary method for the detection and visualization of foreign bodies in the pulmonary artery because it provides high sensitivity and accuracy. It is very difficult to diagnose a patient with a non-iatrogenic pulmonary artery foreign body who does not have a history of a penetrating trauma. This case report describes a 36-year-old male that presented with coughing and haemoptysis. Based on conventional coronal and cross-sectional CT, the foreign body was misdiagnosed as pulmonary tuberculosis and pulmonary artery thrombosis. During treatment of the bronchial artery embolization and anti-tuberculosis therapy, the patient continued to experience haemoptysis. After further analysis of the pulmonary artery CT angiography images and curved multiplane reconstruction, an approximately 6-cm long toothpick was identified in the pulmonary artery with an unclear entry route. After surgery to remove the toothpick, symptoms of coughing and haemoptysis were resolved. This current case demonstrated that multiplane reconstruction in MSCT can improve the detection and visualization of pulmonary artery foreign bodies, which can aid in the diagnosis of pulmonary artery diseases of unknown cause.

Hypo-osmolality activates Wnt/ß-catenin mediated by AQP1 in nucleus pulposus cells degeneration.

The goals of this study were to investigate whether Wnt/ß-catenin signaling plays a role in hypo-osmolality-related degeneration of nucleus pulposus (NP) cells, and if so, to define the mechanism underlying AQP1 in this effect. Human NP cells were cultured under hypo-osmotic (300/350/400 mOsm) and iso-osmotic (450 mOsm) conditions. The cell viability, AQP1, the expression of Wnt/ß-catenin signaling, collagen II/I, and MMP3/9 were evaluated. To determine the effects of the Wnt/ß-catenin signaling, we used the inhibitor and the activator of Wnt during the hypo-osmotic culture of NP cells. We also examined whether the silencing and overexpressing of the AQP1 gene would affect the Wnt/ß-catenin expression in NP cells. Hypo-osmolality caused NP cell degeneration and activated the Wnt/ß-catenin signaling but suppressed the AQP1 level. Inhibiting the Wnt/ß-catenin signaling alleviated the hypo-osmolality-induced NP cell degeneration. On the contrary, activating Wnt/ß-catenin aggravated the NP cell degeneration under hypo-osmotic conditions, which did not affect AQP1 expression. AQP1-overexpressed NP cells exhibited decreased Wnt/ß-catenin signaling and alleviated cell degeneration under the hypo-osmotic condition. Besides, AQP1 silencing accelerated NP cell degeneration and activated Wnt/ß-catenin expression compared with untreated control. Hypo-osmolality promotes NP cell degeneration via activating Wnt/ß-catenin signaling, which is suppressed by AQP1 expression. The upregulation of AQP1 suppressed the Wnt/ß-catenin signaling and alleviated the hypo-osmolality induced by the NP cell degeneration.