The changing of α5-GABAA receptors expression and distribution participate in sevoflurane-induced learning and memory impairment in young mice.

BACKGROUND: Sevoflurane is a superior agent for maintaining anesthesia during surgical procedures. However, the neurotoxic mechanisms of clinical concentration remain poorly understood. Sevoflurane can interfere with the normal function of neurons and synapses and impair cognitive function by acting on α5-GABAAR. METHODS: Using MWM test, we evaluated cognitive abilities in mice following 1 h of anesthesia with 2.7%-3% sevoflurane. Based on hippocampal transcriptome analysis, we analyzed the differential genes and IL-6 24 h post-anesthesia. Western blot and RT-PCR were performed to measure the levels of α5-GABAAR, Radixin, P-ERM, P-Radixin, Gephyrin, IL-6, and ROCK. The spatial distribution and expression of α5-GABAAR on neuronal somata were analyzed using histological and three-dimensional imaging techniques. RESULTS: MWM test indicated that partial long-term learning and memory impairment. Combining molecular biology and histological analysis, our studies have demonstrated that sevoflurane induces immunosuppression, characterized by reduced IL-6 expression levels, and that enhanced Radixin dephosphorylation undermines the microstructural stability of α5-GABAAR, leading to its dissociation from synaptic exterior and resulting in a disordered distribution in α5-GABAAR expression within neuronal cell bodies. On the synaptic cleft, the expression level of α5-GABAAR remained unchanged, the spatial distribution became more compact, with an increased fluorescence intensity per voxel. On the extra-synaptic space, the expression level of α5-GABAAR decreased within unchanged spatial distribution, accompanied by an increased fluorescence intensity per voxel. CONCLUSION: Dysregulated α5-GABAAR expression and distribution contributes to sevoflurane-induced partial long-term learning and memory impairment, which lays the foundation for elucidating the underlying mechanisms in future studies.

Potential Common Mechanisms of Cytotoxicity Induced by Organophosphorus Pesticides via NLRP3 Inflammasome Activation.

The Multi-Threat Medical Countermeasure (MTMC) technique is crucial for developing common biochemical signaling pathways, molecular mediators, and cellular processes. This study revealed that the Nod-like receptor 3 (NLRP3) inflammasome pathway may be a significant contributor to the cytotoxicity induced by various organophosphorus pesticides (OPPs). The study demonstrated that exposure to six different types of OPPs (paraoxon, dichlorvos, fenthion, dipterex, dibrom, and dimethoate) led to significant cytotoxicity in BV2 cells, which was accompanied by increased expression of NLRP3 inflammasome complexes (NLRP3, ASC, Caspase-1) and downstream inflammatory cytokines (IL-1ß, IL-18), in which the order of cytotoxicity was dichlorvos > dipterex > dibrom > paraoxon > fenthion > dimethoate, based on the IC50 values of 274, 410, 551, 585, 2,158, and 1,527,566 µM, respectively. The findings suggest that targeting the NLRP3 inflammasome pathway could be a potential approach for developing broad-spectrum antitoxic drugs to combat multi-OPPs-induced toxicity. Moreover, inhibition of NLRP3 efficiently protected the cells against cytotoxicity induced by these six OPPs, and the expression of NLRP3, ASC, Caspase-1, IL-1ß, and IL-18 decreased accordingly. The order of NLRP3 affinity for OPPs was dimethoate > paraoxon > dichlorvos > dibrom > (fenthion and dipterex) based on K D values of 89.8, 325, 1,460, and 2,690 µM, respectively. Furthermore, the common molecular mechanism of NLRP3-OPPs was clarified by the presence of toxicity effector groups (benzene ring, nitrogen/oxygen-containing functional group); =O, -O-, or =S (active) groups; and combination residues (Gly271, Asp272). This finding provided valuable insights into exploring the common mechanisms of multiple threats and developing effective therapeutic strategies to prevent OPPs poisoning.

A mix & act liposomes of phospholipase A2-phosphatidylserine for acute brain detoxification by blood‒brain barrier selective-opening.

In the treatment of central nervous system disease, the blood-brain barrier (BBB) is a major obstruction to drug delivery that must be overcome. In this study, we propose a brain-targeted delivery strategy based on selective opening of the BBB. This strategy allows some simple bare nanoparticles to enter the brain when mixed with special opening material; however, the BBB still maintains the ability to completely block molecules from passing through. Based on the screening of BBB opening and matrix delivery materials, we determined that phospholipase A2-catalyzed 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine liposomes can efficiently carry drugs into the brain immediately. At an effective dose, this delivery system is safe, especially with its effect on the BBB being reversible. This mix & act delivery system has a simple structure and rapid preparation, making it a strong potential candidate for drug delivery across the BBB.

Role of transient receptor potential ankyrin 1 in idiopathic pulmonary fibrosis: modulation of M2 macrophage polarization.

Idiopathic pulmonary fibrosis (IPF) poses significant challenges due to limited treatment options despite its complex pathogenesis involving cellular and molecular mechanisms. This study investigated the role of transient receptor potential ankyrin 1 (TRPA1) channels in regulating M2 macrophage polarization in IPF progression, potentially offering novel therapeutic targets. Using a bleomycin-induced pulmonary fibrosis model in C57BL/6J mice, we assessed the therapeutic potential of the TRPA1 inhibitor HC-030031. TRPA1 upregulation was observed in fibrotic lungs, correlating with worsened lung function and reduced survival. TRPA1 inhibition mitigated fibrosis severity, evidenced by decreased collagen deposition and restored lung tissue stiffness. Furthermore, TRPA1 blockade reversed aberrant M2 macrophage polarization induced by bleomycin, associated with reduced Smad2 phosphorylation in the TGF-ß1-Smad2 pathway. In vitro studies with THP-1 cells treated with bleomycin and HC-030031 corroborated these findings, highlighting TRPA1's involvement in fibrotic modulation and macrophage polarization control. Overall, targeting TRPA1 channels presents promising therapeutic potential in managing pulmonary fibrosis by reducing pro-fibrotic marker expression, inhibiting M2 macrophage polarization, and diminishing collagen deposition. This study sheds light on a novel avenue for therapeutic intervention in IPF, addressing a critical need in the management of this challenging disease.

FTIR microspectroscopic study of gastric cancer AGS cells apoptosis induced by As2O3.

As2O3 has shown significant anti-gastric cancer effects, but the mechanism is still unclear. Thus, biomacromolecular changes induced by As2O3 were investigated by using human gastric cancer AGS cells as the model. Flow cytometry results confirmed that As2O3 induced AGS cells apoptosis. Fourier transform infrared (FTIR) microspectroscopy detected biomacromolecular changes during As2O3-induced AGS cells apoptosis sensitively: IR spectra showed significant changes in the lipids content and the proteins and DNA structure. Peak-area ratios indicated obvious changes in the lipids and DNA content and the proteins structure, while also showing a relatively good linear relationship between A1733/A969 and the apoptosis rate. PCA exhibited significant alteration in nucleic acids while curve fitting further revealed the changes in nucleic acids and proteins. On the whole, our study explored As2O3-induced gastric cancer cells apoptosis in depth on the basis of analyzing biomacromolecular changes, in addition, it also suggested FTIR microspectroscopy to be possibly useful in the research of apoptosis.

Predictive role of glycocalyx components and MMP-9 in cardiopulmonary bypass patients for ICU stay.

Background: Shedding of glycocalyx is relevant to worse prognosis in surgical patients, and elevated levels of serum matrix metalloproteinase-9 (MMP-9) are associated with this phenomenon. This study aimed to investigate the dynamic alterations of serum glycocalyx components and MMP-9 during cardiopulmonary bypass (CPB), and evaluate their predictive capacities for prolonged intensive care unit (ICU) stay, as well as their correlation with coagulation dysfunction. Methods: This retrospective study analyzed serum levels of syndecan-1, heparan sulfate (HS), and MMP-9 at different time points during CPB, and assessed their association with prolonged ICU stay and coagulation dysfunction. Results: Syndecan-1, HS, and MMP-9 exhibited divergent changes during CPB. Serum levels of syndecan-1 (AUC = 78.0 %) and MMP-9 (AUC = 78.4 %) were validated as reliable predictors for prolonged ICU stay, surpassing the predictive value of creatinine (AUC = 70.0 %). Syndecan-1 (rho = 0.566, P < 0.01 at T1 and rho = 0.526, P < 0.01 at T2) and HS (rho = 0.403, P < 0.05 at T4) exhibited correlations with activated partial thromboplastin time (APTT) ratio beyond the normal range. Conclusions: Our findings advocate the potential efficacy of serum glycocalyx components and MMP-9 as early predictive indicators for extended ICU stay following cardiac surgery with CPB. Additionally, we observed a correlation between glycocalyx disruption during CPB and coagulation dysfunction. Further studies with expansive cohorts are warranted to consolidate our findings and explore the predictive potential of other glycocalyx components.

Bioengineering Approaches for the Pancreatic Tumor Organoids Research and Application.

Pancreatic cancer is a highly lethal form of digestive malignancy that poses significant health risks to individuals worldwide. Chemotherapy-based comprehensive treatment is the primary therapeutic approach for midlife and late-life patients. Nevertheless, the heterogeneity of the tumor and individual genetic backgrounds result in substantial variations in drug sensitivity among patients, rendering a single treatment regimen unsuitable for all patients. Conventional pancreatic cancer tumor organoid models are capable of emulating the biological traits of pancreatic cancer and are utilized in drug development and screening. However, these tumor organoids can still not mimic the tumor microenvironment (TME) in vivo, and the poor controllability in the preparation process hinders translation from essential drug screening to clinical pharmacological therapy. In recent years, many engineering methods with remarkable results have been used to develop pancreatic cancer organoid models, including bio-hydrogel, co-culture, microfluidic, and gene editing. Here, this work summarizes and analyzes the recent developments in engineering pancreatic tumor organoid models. In addition, the future direction of improving engineered pancreatic cancer organoids is discussed for their application prospects in clinical treatment.

A Sirtuin-Dependent T7 RNA Polymerase Variant.

Transcriptional regulation is of great significance for cells to maintain homeostasis and, meanwhile, represents an innovative but less explored means to control biological processes in synthetic biology and bioengineering. Herein we devised a T7 RNA polymerase (T7RNAP) variant through replacing an essential lysine located in the catalytic core (K631) with Nε-acetyl-l-lysine (AcK) via genetic code expansion. This T7RNAP variant requires the deacetylase activity of NAD-dependent sirtuins to recover its enzymatic activities and thereby sustains sirtuin-dependent transcription of the gene of interest in live cells including bacteria and mammalian cells as well as in in vitro systems. This T7RNAP variant could link gene transcription to sirtuin expression and NAD availability, thus holding promise to support some relevant research.

Liposome-Based Silibinin for Mitigating Nonalcoholic Fatty Liver Disease: Dual Effects via Parenteral and Intestinal Routes.

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological entity that is typically characterized by intrahepatic ectopic steatosis. Nowadays, NAFLD has surpassed viral hepatitis and become the most common chronic liver disease worldwide, which poses a great threat to human health. Silibinin (Sil), a well-known natural product, has been widely used in clinical treatment for liver disorders and exhibited therapeutic potential for NAFLD. However, the suitability of Sil for NAFLD treatment still requires further investigation due to its limited absorption and low bioavailability. This study aimed to construct a Sil-loaded liposome (Sil-Lip) to overcome the limitations of Sil, thereby enhancing its beneficial effects on NAFLD and then investigate the underlying mechanisms of action of Sil-Lip. Herein, Sil-Lip was fabricated by a well-established thin-film dispersion method and carefully characterized, followed by evaluating their therapeutic efficacy using high-fat diet-induced NAFLD mice and free fatty acid -stimulated HepG2 cells. Then, liver transcriptome analysis and 16S ribosomal RNA (16S rRNA) sequencing were utilized to elucidate the potential mechanisms of action of Sil-Lip. Our data indicated that Sil-Lip harbored good gastrointestinal tract stability, mucus layer permeation, and excellent oral absorption and bioavailability. In vivo and in vitro NAFLD models demonstrated that Sil-Lip had better effects in alleviating lipid metabolism disorders, insulin resistance, and inflammation than did Sil alone. Further investigations revealed that the beneficial effects of Sil-Lip were mediated by modulating intrahepatic insulin resistance-related and nuclear factor-kappa B (NF-κB) signaling pathways and extrahepatic gut microbiota. Our study confirmed that Sil-Lip can effectively improve the absorption and bioavailability of Sil, resultantly potentiating its ameliorative effects on NAFLD through modulating intrahepatic insulin resistance-related and NF-κB signaling pathways and extrahepatic gut microbiota.

Animal Use Strategies in the Longshan Mountain Region of Northern China during the First Millennium BC: A Zooarchaeological Analysis of Yucun.

The first millennium BC saw the expansion of the Western Zhou dynasty in its northwestern frontier, alongside the rise and development of the Qin State in the Longshan Mountain region of northern China. Exploring the subsistence practices of these communities is crucial to gaining a better understanding of the social, cultural, and political landscape in this region at the time. While much of the research to date has focused on the Qin people, the subsistence practices of the Zhou people remain poorly understood. In this study, we analyzed animal remains from Yucun, a large settlement site associated with the Zhou people, located to the east of the Longshan Mountain. These animal remains were recovered in the excavation seasons of 2018-2020. Our results show that pigs, dogs, cattle, caprines, and horses, which were the major domestic animals at Yucun, accounted for over 90.8% of the animal remains examined in terms of the number of identified specimens (NISP) and 72.8% in terms of the minimum number of individuals (MNI), with cattle and caprines playing dominant roles. In terms of the taxonomic composition and the mortality profiles of pigs, caprines, and cattle, Yucun shared similarities with Maojiaping and Xishan, two contemporaneous Qin cultural sites located to the west of the Longshan Mountain, and differ from other farming societies in the middle and lower reaches of the Yellow River valley. Considering the cultural attributes and topographic conditions of these various sites, these findings imply that environmental conditions may have played a more significant role than cultural factors in shaping the animal-related subsistence practices in northern China during the first millennium BC.

Noninvasive prenatal screening with conventional sequencing depth to screen fetal copy number variants: A retrospective study of 19 144 pregnant women.

AIM: To investigate the detectability of noninvasive prenatal screening (NIPS) with conventional sequencing depth to detect fetal copy number variants. METHODS: We performed a retrospective study in a total of 19 144 pregnant women. Their cell-free plasma DNA were assessed for trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidies, and genome-wide copy number variants by NIPS at conventional sequencing depth. RESULTS: Three hundred seventy-four cases (2.0%, 374/19 144) with abnormal results were detected, which including 84 cases (0.4%, 84/19 144) with high risk of trisomy 21, 18, and 13, 90 cases (0.5%, 90/19 144) with high risk of sex chromosome abnormalities (SCA), and 44 cases (0.2%, 44/19 144) with high risk of other chromosome aneuploidies. One hundred fifty-six cases (0.8%, 156/19 144) with high risk of copy number variations (CNVs) were also detected. In following prenatal diagnosis, composite positive predictive value (PPV) of trisomy 21, 18, and 13 was 69.6% (48/69). The PPV of SCAs was 37.3% (19/51). And the PPVs for CNVs was detected as 51.0% (<5 Mb), 71.4% (5 Mb ≤ CNV ≤10 Mb), 56.5% (>10 Mb). Finally, a follow-up about the pregnancy outcomes were conducted for all available cases. CONCLUSIONS: NIPS yielded high PPVs for trisomy 21, 18, and 13 aneuploidies and moderate PPVs for SCAs and CNVs. The screening effectiveness was closely related to the size of CNV fragments. Larger CNVs, especially larger than 5 Mb, could be detected more accurately by NIPS in our analytic technique. Meanwhile, diagnostic confirmation by microarray analysis was highly recommended.

Tailoring biomaterials for biomimetic organs-on-chips.

Organs-on-chips are microengineered microfluidic living cell culture devices with continuously perfused chambers penetrating to cells. By mimicking the biological features of the multicellular constructions, interactions among organs, vascular perfusion, physicochemical microenvironments, and so on, these devices are imparted with some key pathophysiological function levels of living organs that are difficult to be achieved in conventional 2D or 3D culture systems. In this technology, biomaterials are extremely important because they affect the microstructures and functionalities of the organ cells and the development of the organs-on-chip functions. Thus, herein, we provide an overview on the advances of biomaterials for the construction of organs-on-chips. After introducing the general components, structures, and fabrication techniques of the biomaterials, we focus on the studies of the functions and applications of these biomaterials in the organs-on-chips systems. Applications of the biomaterial-based organs-on-chips as alternative animal models for pharmaceutical, chemical, and environmental tests are described and highlighted. The prospects for exciting future directions and the challenges of biomaterials for realizing the further functionalization of organs-on-chips are also presented.

Phosphoproteome reveals long-term potentiation deficit following treatment of ultra-low dose soman exposure in mice.

Soman, a warfare nerve agent, poses a significant threat by inducing severe brain damage that often results in death. Nonetheless, our understanding of the biological changes underlying persistent neurocognitive dysfunction caused by low dosage of soman remains limited. This study used mice to examine the effects of different doses of soman over time. Phosphoproteomic analysis of the mouse brain is the first time to be used to detect toxic effects of soman at such low or ultra-low doses, which were undetectable based on measuring the activity of acetylcholinesterase at the whole-animal level. We also found that phosphoproteome alterations could accurately track the soman dose, irrespective of the sampling time. Moreover, phosphoproteome revealed a rapid and adaptive cellular response to soman exposure, with the points of departure 8-38 times lower than that of acetylcholinesterase activity. Impaired long-term potentiation was identified in phosphoproteomic studies, which was further validated by targeted quantitative proteomics, immunohistochemistry, and immunofluorescence analyses, with significantly increased levels of phosphorylation of protein phosphatase 1 in the hippocampus following soman exposure. This increase in phosphorylation inhibits long-term potentiation, ultimately leading to long-term memory dysfunction in mice.

Prenatal diagnosis of a case with complete and uniform tetrasomy 12p by the utility of noninvasive prenatal testing.

PURPOSE: To report a rare type of Pallister-Killian syndrome (PKS) diagnosed prenatally by the utility of non-invasive prenatal testing (NIPT). METHODS: NIPT was performed in the first trimester. Conventional karyotyping and chromosomal microarray analysis (CMA) were performed on the amniotic samples in the second trimester. Copy number variation sequencing (CNV-seq) was used for the validation of fetal skin and the placental tissue after pregnancy termination. RESULTS: NIPT results showed increased signal from chromosome 12p. Subsequent prenatal diagnostic testing by karyotype revealed 47, XY, +i (12p), and CMA displayed four copies of 12p: 12p13.33-12p11.1(173786_34835641) × 4. The CNV-seq results of the fetal skin and the fetal side of placenta showed four copies of 12p13.33-p11 and an estimated chimeric duplication of 34.08 Mb (chimerism ratio: 10%) in 12 p13.33-p11, respectively. However, no abnormality was detected by CNV-seq at the maternal side of placenta. CONCLUSIONS: Our findings suggest that a positive signal from chromosome 12p on NIPT should raise suspicion for PKS. With the wide application of NIPT, the true positive of incidental finding is expected to increase.

Living Anisotropic Structural Color Hydrogels for Cardiotoxicity Screening.

Environmental toxins can result in serious and fatal damage in the human heart, while the development of a viable stratagem for assessing the effects of environmental toxins on human cardiac tissue is still a challenge. Herein, we present a heart-on-a-chip based on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) cultured living anisotropic structural color hydrogels for cardiotoxicity screening. Such anisotropic structural color hydrogels with a conductive parallel carbon nanotube (CNT) upper layer, gelatin methacryloyl (GelMA) interlayer, and inverse opal bottom layer were fabricated by a sandwich replicating approach. The inverse opal structure endowed the anisotropic hydrogels with stable structural color property, while the parallel and conductive CNTs could induce the hiPSC-CMs to grow in a directional manner with consistent autonomous beating. Notably, the resultant hiPSC-CM-cultured hydrogel exhibited synchronous shifts in structural color, responding to contraction and relaxation of hiPSC-CMs, offering a visual platform for monitoring cell activity. Given these features, the hiPSC-CM-cultured living anisotropic structural color hydrogels were integrated into a heart-on-a-chip, which provided a superior cardiotoxicity screening platform for environmental toxins.

Biomimetic Alveoli System with Vivid Mechanical Response and Cell-Cell Interface.

Alveolar microenvironmental models are important for studying the basic biology of the alveolus, therapeutic trials, and drug testing. However, a few systems can fully reproduce the in vivo alveolar microenvironment including dynamic stretching and the cell-cell interface. Here, a novel biomimetic alveolus-on-a-chip microsystem is presented suitable for visualizing physiological breathing for simulating the 3D architecture and function of human pulmonary alveoli. This biomimetic microsystem contains an inverse opal structured polyurethane membrane that achieves real-time observation of mechanical stretching. In this microsystem, the alveolar-capillary barrier is created by alveolar type 2 (ATII) cells cocultured with vascular endothelial cells (ECs) on this membrane. Based on this microsystem, the phenomena of flattening and the tendency of differentiation in ATII cells are observed. The synergistic effects of mechanical stretching and ECs on the proliferation of ATII cells are also observed during the repair process following lung injury. These features indicate the potential of this novel biomimetic microsystem for exploring the mechanisms of lung diseases, which can provide future guidance concerning drug targets for clinical therapies.

Negatively charged phospholipids doped liposome delivery system for mRNA with high transfection efficiency and low cytotoxicity.

Messenger RNA (mRNA) has become one of the most potential drugs in recent years. However, efficient and safe delivery of fragile and easily degradable mRNA is a major challenge. Appropriate delivery system (DS) determines the final effect of mRNA. Cationic lipids play a crucial and decisive role in the entire DS, but also cause huge biosafety problems due to the high toxicity. In this study, a new DS for mRNA delivery that combines negatively charged phospholipids was developed in order to neutralize the positive charge and thus increase the safety. Further, the factors affecting mRNA transfection from cell to animal were investigated. The mRNA DS with optimum condition of lipid composition, proportions, structure, and transfection time was synthesized. Adding an appropriate amount of the anionic lipid to liposomes could increase the safety while maintaining the original transfection efficiency. For transporting mRNA in vivo, requirements regarding the mRNA encapsulation and releasing rate should be further considered to optimize DS design and preparation.

Activated Carbon nanoparticles Loaded with Metformin for Effective Against Hepatocellular Cancer Stem Cells.

Introduction: Hepatocellular cancer stem cells (CSCs) play crucial roles in hepatocellular cancer initiation, development, relapse, and metastasis. Therefore, eradication of this cell population is a primary objective in hepatocellular cancer therapy. We prepared a nanodrug delivery system with activated carbon nanoparticles (ACNP) as carriers and metformin (MET) as drug (ACNP-MET), which was able to selectively eliminate hepatocellular CSCs and thereby increase the effects of MET on hepatocellular cancers. Methods: ACNP were prepared by ball milling and deposition in distilled water. Suspension of ACNP and MET was mixed and the best ratio of ACNP and MET was determined based on the isothermal adsorption formula. Hepatocellular CSCs were identified as CD133+ cells and cultured in serum-free medium. We investigated the effects of ACNP-MET on hepatocellular CSCs, including the inhibitory effects, the targeting efficiency, self-renewal capacity, and the sphere-forming capacity of hepatocellular CSCs. Next, we evaluated the therapeutic efficacy of ACNP-MET by using in vivo relapsed tumor models of hepatocellular CSCs. Results: The ACNP have a similar size, a regular spherical shape and a smooth surface. The optimal ratio for adsorption was MET: ACNP=1:4. ACNP-MET could target and inhibit the proliferation of CD133+ population and decrease mammosphere formation and renewal of CD133+ population in vitro and in vivo. Conclusion: These results not only suggest that nanodrug delivery system increased the effects of MET, but also shed light on the mechanisms of the therapeutic effects of MET and ACNP-MET on hepatocellular cancers. ACNP, as a good nano-carrier, could strengthen the effect of MET by carrying drugs to the micro-environment of hepatocellular CSCs.

In situ gelling hydrogel loaded with berberine liposome for the treatment of biofilm-infected wounds.

Background: In recent years, the impact of bacterial biofilms on traumatic wounds and the means to combat them have become a major research topic in the field of medicine. The eradication of biofilms formed by bacterial infections in wounds has always been a huge challenge. Herein, we developed a hydrogel with the active ingredient berberine hydrochloride liposomes to disrupt the biofilm and thereby accelerate the healing of infected wounds in mice. Methods: We determined the ability of berberine hydrochloride liposomes to eradicate the biofilm by means of studies such as crystalline violet staining, measuring the inhibition circle, and dilution coating plate method. Encouraged by the in vitro efficacy, we chose to coat the berberine hydrochloride liposomes on the Poloxamer range of in-situ thermosensitive hydrogels to allow fuller contact with the wound surface and sustained efficacy. Eventually, relevant pathological and immunological analyses were carried out on wound tissue from mice treated for 14 days. Results: The final results show that the number of wound tissue biofilms decreases abruptly after treatment and that the various inflammatory factors in them are significantly reduced within a short period. In the meantime, the number of collagen fibers in the treated wound tissue, as well as the proteins involved in healing in the wound tissue, showed significant differences compared to the model group. Conclusion: From the results, we found that berberine liposome gel can accelerate wound healing in Staphylococcus aureus infections by inhibiting the inflammatory response and promoting re-epithelialization as well as vascular regeneration. Our work exemplifies the efficacy of liposomal isolation of toxins. This innovative antimicrobial strategy opens up new perspectives for tackling drug resistance and fighting wound infections.

Treatment of Idiopathic Pulmonary Fibrosis by Inhaled Silybin Dry Powder Prepared via the Nanosuspension Spray Drying Technology.

Idiopathic pulmonary fibrosis (IPF) is a kind of life-threatening interstitial lung disease characterized by progressive dyspnea with accurate pathogenesis unknown. At present, heat shock protein inhibitors are gradually used to treat IPF. Silybin, a heat shock protein C-terminal inhibitor, has high safety and good application prospects. In this work, we have developed a silybin powder able to be used for inhalation administration for the treatment of IPF. Silybin powder was prepared by the spray drying method and identified using cascade impactometry, particle size, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR) spectroscopy. A rat model of bleomycin-induced IPF was used to assess the effect of inhaled silybin spray-dried powder. Lung hydroxyproline content, wet weight, histology, inflammatory factor expression, and gene expression were examined. The results showed that inhaled silybin spray-dried powder alleviated inflammation and fibrosis, limited hydroxyproline accumulation in the lungs, modulated gene expression in the development of IPF, and improved postoperative survival. The results of this study suggest that silybin spray-dried powder is an attractive candidate for the treatment of IPF.