Solar transpiration-powered lithium extraction and storage.

Lithium mining is energy intensive and environmentally costly. This is because lithium ions are typically present in brines as a minor component mixed with physiochemically similar cations that are difficult to separate. Inspired by nature's ability to selectively extract species in transpiration, we report a solar transpiration-powered lithium extraction and storage (STLES) device that can extract and store lithium from brines using natural sunlight. Specifically, the device uses a hierarchically structured solar transpirational evaporator to create a pressure gradient, which allows for the extraction of lithium from brines through a membrane and its storage in a vascular storage layer. Long-term experiments, various membrane tests, and different size assessments demonstrate the stability, compatibility, and scalability of STLES. This solar-powered mining technology provides an alternative developing pathway toward the sustainable extraction of critical resources.

Phytochemical and Flavor Characteristics of Mulberry Juice Fermented with Lactiplantibacillus plantarum BXM2.

Fermentation of mulberry juice not only improves its shelf life, but also effectively enhances their flavor and nutritional quality. This study elucidated the phytochemical and flavor characteristics of mulberry juice fermented with Lactiplantibacillus plantarum BXM2, originally isolated from naturally fermented fruit beverage, through widely targeted metabolomics. The fermentation produced the unique flavor of fermented juice and decreased the pH from 4.15 to 3.19. The metabolomic analysis detected 907 non-volatile metabolites, from which 359 significantly different non-volatile metabolites (up 238, down 121) were screened out. Among 731 identified volatile metabolites, 26 flavor substances were the major contributors to the flavor differences between fermented and unfermented mulberry juices. It is hypothesized that lipid metabolism and amino acid catabolism are crucial pathways for the flavor enhancement of mulberry juice fermented with L. plantarum BXM2. Meanwhile, significant increases of the contents of a variety of bioactive substances, such as indole-3-lactic acid, octadeca-9,12,15-trienoic acid, di-/tri-peptides, etc., conferred additional health potential to BXM2-fermented mulberry juice.

miR-19a-3p promotes the growth of hepatocellular carcinoma by regulating p53/SOX4.

Objective: This study aims to investigate the potential functions of miR-19a-3p in HCC. Method: We collected serum samples to analyze miR-19a-3p expression. We utilized CCK8 and Transwell assays to access miR-19a-3p's influence on HCC cells malignancy. We used dual-luciferase reporter and western blotting to validate the impact of p53/miR-19 on miR-19/SOX4. Results: The results demonstrated that miR-19a-3p was highly expressed in pre-operative serum samples and HCC cells, which can promote cell proliferation, migration and invasion in HCC under in vitro conditions. Additionally, there was a p53 binding site on the upstream of miR-19a-3p, which was inhibited by p53. SOX4 was the direct gene targeted by miR-19a-3p. The imbalance of p53-miR-19-SOX4 loop was one reason for the progress of HCC. Conclusion: Our findings validate the mechanisms of miR-19a-3p and highlight its potential as a therapeutic target in HCC.

In Vitro Characterization and Identification of Potential Probiotic Yeasts Isolated from Zaopocu, a Traditional Fermented Dregs Vinegar from Hainan Island.

Recently, there has been an increasing interest in researching fermented food-derived yeasts as probiotics because they offer a natural and diverse source of potential strains with unique functional properties and health benefits. In this study, 13 yeast strains isolated from Zaopocu (ZPC), a traditional fermented dregs vinegar on Hainan Island, China, were evaluated for their probiotic characteristics in vitro. Yeast identification was conducted through 5.8S-ITS region sequencing, revealing Kodamaea ohmeri as the predominantly isolated species (ZPC_Y3, Y5, Y6, Y11), followed by Pichia kudriavzevii (ZPC_Y2, Y13, Y14), Rhodotorula mucilaginosa (ZPC_Y9, Y10), Pichia fermentans (ZPC_Y8, Y12), Pichia kluyveri (ZPC_Y4), and Pichia occidentalis (ZPC_Y1). Except for ZPC_Y4, ZPC_Y8, and ZPC_Y12, all isolated yeasts exhibited stable growth at 37 °C. The survival rates of all test strains exceeded 60% under challenging conditions at pH = 2 and 0.3% bile salt, along with strong antioxidant activity (> 5 6%), notable autoaggregation (> 70%), and varying levels of cell hydrophobicity with xylene (ranging from 35.32 ± 8.57% to 89.73 ± 4.84%). In addition, all isolates showed resistance to multiple antibiotics, along with antagonistic activity, and were deemed safe as none exhibited hemolytic, gelatinase, or DNase activities. Significantly, two P. kudriavzevii strains (ZPC_Y2, Y14) exhibited the production of catalase, lipase, and ß-galactosidase, along with the capacity to synthesize gamma-aminobutyric acid (GABA). In summary, this preliminary study represents the first attempt to identify and characterize potential probiotic yeast strains isolated from Zaopocu, providing a theoretical basis for exploring their application in developing novel therapeutic probiotics.

Electroacupuncture improves cognitive impairment after ischemic stroke based on regulation of mitochondrial dynamics through SIRT1/PGC-1α pathway.

In recent years, the mechanism of acupuncture in the treatment of post-stroke cognitive impairment (PSCI) has not been fully elucidated. The balance between mitochondrial fission and fusion is important for PSCI. Our previous research demonstrated that electroacupuncture can improve learning and memory in middle cerebral artery ischemia reperfusion (MCAO/R) rats. However, the specific mechanism by which electroacupuncture improves learning and memory in MCAO/R rats by regulating mitochondrial fission and fusion needs to be further investigated. The MCAO/R rats was developed using the line-bolt method. The rats were randomly divided into sham-operated (Sham), model (MCAO/R), electroacupuncture (MCAO/R + EA) and sham-electroacupuncture (MCAO/R + sham EA) groups. Investigating the effects of EA on the expression of Sirtuin1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), Optic atrophy 1R + (OPA1) and Dynamin-related protein 1 (DRP1) in hippocampal neurons and on the morphology and function of hippocampal neurons and mitochondria. EA was able to reduce neurologic deficit scores and cerebral infarct volume and improve new object discrimination in MCAO/R rats, but there were no significant changes in these indices in the sham-electroacupuncture group. Moreover, EA increased the expression of SIRT1, PGC-1α, and OPA1 in hippocampal tissues, inhibited the expression of DRP1, attenuated neuronal and mitochondrial damage, and reduced mitochondrial fragmentation. The mechanism by which EA improves learning memory deficits in MCAO/R rats may be related to the inhibition of SIRT1/PGC-1α expression, the enhancement of mitochondrial fusion and the obstruction of its fission, and the reduction of hippocampal neuronal damage.

Approaches to scarless burn wound healing: application of 3D printed skin substitutes with dual properties of anti-infection and balancing wound hydration levels.

BACKGROUND: Severe burn wounds face two primary challenges: dysregulated cellular impairment functions following infection and an unbalanced wound hydration microenvironment leading to excessive inflammation and collagen deposition. These results in hypertrophic scar contraction, causing significant deformity and disability in survivors. METHODS: A three-dimensional (3D) printed double-layer hydrogel (DLH) was designed and fabricated to address the problem of scar formation after burn injury. DLH was developed using methacrylated silk fibroin (SFMA) and gelatin methacryloyl (GelMA) for the upper layer, and GelMA and hyaluronic acid methacryloyl (HAMA) for the lower layer. To combat infection, copper-epigallocatechin gallate (Cu-EGCG) was incorporated into the lower layer bioink, collectively referred to as DLS. To balance wound hydration levels, HaCaT cells were additionally encapsulated in the upper layer, designed as DLS/c. FINDINGS: DLH demonstrated suitable porosity, appropriate mechanical properties, and excellent biocompatibility. DLS exhibited potent antimicrobial properties, exerted anti-inflammatory effects by regulating macrophage polarisation, and may enhance angiogenesis through the HIF-1α/VEGF pathway. In the DLS/c group, animal studies showed significant improvements in epidermal formation, barrier function, and epidermal hydration, accompanied by reduced inflammation. In addition, Masson's trichrome and Sirius red staining revealed that the structure and ratio of dermal collagen in DLS/c resembled that of normal skin, indicating considerable potential for scarless wound healing. INTERPRETATION: This biomimetic matrix shows promise in addressing the challenges of burn wounds and aiming for scarless repair, with benefits such as anti-infection, epidermal hydration, biological induction, and optimised topological properties. FUNDING: Shown in Acknowledgements.

Targeting S100A12 to Improve Angiogenesis and Accelerate Diabetic Wound Healing.

Long-term inflammation and impaired angiogenesis are thought to be the causes of delayed healing or nonhealing of diabetic wounds. S100A12 is an essential pro-inflammatory factor involved in inflammatory reactions and serves as a biomarker for various inflammatory diseases. However, whether high level of S100A12 exists in and affects the healing of diabetic wounds, as well as the underlying molecular mechanisms, remain unclear. In this study, we found that the serum concentration of S100A12 is significantly elevated in patients with type 2 diabetes. Exposure of stratified epidermal cells to high glucose environment led to increased expression and secretion of S100A12, resulting in impaired endothelial function by binding to the advanced glycation endproducts (RAGE) or Toll-like receptor 4 (TLR4) on endothelial cell. The transcription factor Krüpple-like Factor 5 (KLF5) is highly expressed in the epidermis under high glucose conditions, activating the transcriptional activity of the S100A12 and boost its expression. By establishing diabetic wounds model in alloxan-induced diabetic rabbit, we found that local inhibition of S100A12 significantly accelerated diabetic wound healing by promoting angiogenesis. Our results illustrated the novel endothelial-specific injury function of S100A12 in diabetic wounds and suggest that S100A12 is a potential target for the treatment of diabetic wounds.

Analytic ellipsometric measurement for materials under bulk encapsulation.

Accurate measurement of the dielectric functions of emerging optical materials is of great importance for advancements in solid-state physics. However, it is rather challenging since most materials are highly active in ambient conditions, which makes in-situ measurements tough. Here, we report an analytical ellipsometry method (AEM) accessible in ambient conditions for measuring the dielectric functions of chemically reactive materials under bulk encapsulation. Taking the highly pursued low-loss plasmonic materials, such as sodium films, as an example, the effectiveness and measuring errors of the proposed AEM have been systematically demonstrated. This verifies AEM's superiority in overcoming the limitations of traditional spectroscopic ellipsometry methodologies, which include complex multi-parameter fitting procedures and the issue of potentially unphysical results, especially in newly developed low-loss materials. Our results will provide a generalized and convenient ellipsometric measurement strategy for sensitive materials under bulk encapsulation.

Association of the systemic immune-inflammation index with anemia: a population-based study.

Background: Inflammation has been reported to be related to anemia. As a novel inflammatory marker, Systemic immune-inflammation index (SII) has not been studied with Anemia. The aim of this study was to investigate the possible relationship between SII and anemia. Methods: This retrospective cross-sectional survey was conducted using data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES) population. In total, 19851 American adults aged ≥18 years were included. SII was calculated as the platelet count×neutrophil count/lymphocyte count. Anemia was defined as hemoglobin (Hgb) levels of < 13 g/dL in males and < 12 g/dL in females. Logistic regression analyses, subgroup analyses and sensitivity analyses were performed to investigate the relationship between SII and anemia. Results: Our study included a total of 19851 patients, of which 1501 (7.6%) had anemia. After adjusting for all covariates, the multivariate logistic regression analysis showed that a higher SII (In-transform) level was associated with increased likelihood of anemia (OR=1.51, 95% CI: 1.36-1.68, P<0.001). The association between SII and anemia exhibited a nonlinear manner. The positive correlation between SII and anemia was related to the severity of anemia. Subgroup analysis showed that there was no significant dependence on age, family income, body mass index, hypertension, kidney disease and cancer except gender on this positive association. Furthermore, sensitivity analyses confirmed the robustness of our results. Conclusion: Our study demonstrated that SII was positively associated with anemia especially among female participants. And this positive correlation was related to the severity of anemia. Further large-scale prospective studies are still needed to analyze the role of SII in anemia.

Alpha-Lipoic Acid Induces Adipose Tissue Browning through AMP-Activated Protein Kinase Signaling in Vivo and in Vitro.

Background: AMP-activated protein kinase (AMPK) is a key enzyme for cellular energy homeostasis and improves metabolic disorders. Brown and beige adipose tissues exert thermogenesis capacities to dissipate energy in the form of heat. Here, we investigated the beneficial effects of the antioxidant alpha-lipoic acid (ALA) in menopausal obesity and the underlying mechanisms. Methods: Female Wistar rats (8 weeks old) were subjected to bilateral ovariectomy (Ovx) and divided into four groups: Sham (n=8), Ovx (n=11), Ovx+ALA2 (n=10), and Ovx+ALA3 (n=6) (ALA 200 and 300 mg/kg/day, respectively; gavage) for 8 weeks. 3T3-L1 cells were used for in vitro study. Results: Rats receiving ALA2 and ALA3 treatment showed significantly lower levels of body weight and white adipose tissue (WAT) mass than those of the Ovx group. ALA improved plasma lipid profiles including triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Hematoxylin & eosin staining of inguinal WAT showed that ALA treatment reduced Ovx-induced adipocyte size and enhanced uncoupling protein 1 (UCP1) expression. Moreover, plasma levels of irisin were markedly increased in ALA-treated Ovx rats. Protein expression of brown fat-specific markers including UCP1, PRDM16, and CIDEA was downregulated by Ovx but markedly increased by ALA. Phosphorylation of AMPK, its downstream acetyl-CoA carboxylase, and its upstream LKB1 were all significantly increased by ALA treatment. In 3T3-L1 cells, administration of ALA (100 and 250 µM) reduced lipid accumulation and enhanced oxygen consumption and UCP1 protein expression, while inhibition of AMPK by dorsomorphin (5 µM) significantly reversed these effects. Conclusion: ALA improves estrogen deficiency-induced obesity via browning of WAT through AMPK signaling.

Novel Near-Infrared Fluorescent Probe for Hepatocyte Growth Factor in Vivo Imaging in Surgical Navigation of Colorectal Cancer.

Despite recent advancements in colorectal cancer (CRC) treatment, the prognosis remains unfavorable primarily due to high recurrence and liver metastasis rates. Fluorescence molecular imaging technologies, combined with specific probes, have gained prominence in facilitating real-time tumor resection guided by fluorescence. Hepatocyte growth factor (HGF) is overexpressed in CRC, but the advancement of HGF fluorescent probes has been impeded by the absence of effective HGF-targeting small-molecular ligands. Herein, we present the targeted capabilities of the novel V-1-GGGK-MPA probe labeled with a near-infrared fluorescent dye, which targets HGF in CRC. The V-1-GGGK peptide exhibits high specificity and selectivity for HGF-positive in vitro tumor cells and in vivo tumors. Biodistribution analysis of V-1-GGGK-MPA revealed tumor-specific accumulation with low background uptake, yielding signal-to-noise ratio (SNR) values of tumor-to-colorectal >6 in multiple subcutaneous CRC models 12 h postinjection. Quantitative analysis confirmed the probe's high uptake in SW480 and HT29 orthotopic and liver metastatic models, with SNR values of tumor-to-colorectal and -liver being 5.6 ± 0.4, 4.6 ± 0.5, and 2.1 ± 0.3, 2.0 ± 0.5, respectively, enabling precise tumor visualization for surgical navigation. Pathological analysis demonstrated the excellent tumor boundaries discrimination capacity of the V-1-GGGK-MPA probe at the molecular level. With its rapid tumor targeting, sustained tumor retention, and precise tumor boundary delineation, V-1-GGGK-MPA merges as a promising HGF imaging agent, enriching the toolbox of intraoperative navigational fluorescent probes for CRC.

Characterization of mechanical stress in the occurrence of cortical opacification in age-related cataracts using three-dimensional finite element model of the human lens and RNA-seq.

Cataract is the leading cause of blindness across the world. Age-related cataract (ARC) is the most common type of cataract, but its pathogenesis is not fully understood. Using three-dimensional finite element modeling combining experimental biotechnology, our study demonstrates that external forces during accommodation cause mechanical stress predominantly in lens cortex, basically matching the localization of opacities in cortical ARCs. We identified the cellular senescence and upregulation of PIEZO1 mRNA in HLECs under mechanical stretch. This mechano-induced senescence in HLECs might be mediated by PIEZO1-related pathways, portraying a potential biomechanical cause of cortical ARCs. Our study updates the fundamental insight towards cataractogenesis, paving the way for further exploration of ARCs pathogenesis and nonsurgical treatment.

Selection and Validation of qRT-PCR Internal Reference Genes to Study Flower Color Formation in Camellia impressinervis.

Real-time quantitative PCR (qRT-PCR) is a pivotal technique for gene expression analysis. To ensure reliable and accurate results, the internal reference genes must exhibit stable expression across varied experimental conditions. Currently, no internal reference genes for Camellia impressinervis have been established. This study aimed to identify stable internal reference genes from eight candidates derived from different developmental stages of C. impressinervis flowers. We employed geNorm, NormFinder, and BestKeeper to evaluate the expression stability of these candidates, which was followed by a comprehensive stability analysis. The results indicated that CiTUB, a tubulin gene, exhibited the most stable expression among the eight reference gene candidates in the petals. Subsequently, CiTUB was utilized as an internal reference for the qRT-PCR analysis of six genes implicated in the petal pigment synthesis pathway of C. impressinervis. The qRT-PCR results were corroborated by transcriptome sequencing data, affirming the stability and suitability of CiTUB as a reference gene. This study marks the first identification of stable internal reference genes within the entire genome of C. impressinervis, establishing a foundation for future gene expression and functional studies. Identifying such stable reference genes is crucial for advancing molecular research on C. impressinervis.

The Efficacy of Tiaoshen Acupuncture in Traditional Chinese Medicine for Insomnia Treatment: A Systematic Review and Meta-analysis.

Background: In recent years, Tiaoshen acupuncture in Traditional Chinese Medicine (TCM) has been employed for treating patients with insomnia, but the clinical efficacy remains to be substantiated. Objective: To assess the efficacy and safety of acupuncture in treating insomnia using the Tiaoshen method in TCM. Design: A systematic review and meta-analysis was conducted. Setting: The research was conducted in Shenzhen. Methods: Electronic databases, including Chinese National Knowledge Infrastructure (CNKI), Wanfang, SinoMed, Weipu, PubMed, Web of Science, EMBASE, and Cochrane databases, were retrieved up to September 15, 2023. Randomized controlled trials (RCTs) meeting inclusion criteria were screened. Quality assessment of included articles was performed using the Cochrane Risk of Bias tool. Valid data were then extracted and analyzed via meta-analysis using Review Manager 5.3. The study was registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 2023100051. Results: A total of 13 articles were included, comprising 849 patients with insomnia (diagnosed as chronic insomnia or primary insomnia). Meta-analysis results indicated that acupuncture with the Tiaoshen method could decrease the Pittsburgh Sleep Quality Index (PSQI) score [RR=-3.03, 95% CI (-3.73, -2.33), P < .00001], hyperarousal (HAS) scale score [RR=-7.75, 95% CI (-12.29, -3.22), P < .0008], and fatigue scale-14 (FS-14) score [RR=-2.11, 95% CI (-2.83, -1.38), P < .00001] compared with superficial acupuncture on non-effective acupoints or conventional acupuncture manipulation. Additionally, acupuncture with the Tiaoshen method demonstrated safety. However, the funnel plot suggested the presence of publication bias. Conclusions: Acupuncture with the Tiaoshen method could enhance sleep quality and efficiency. Due to the low quality of some literature, further high-quality RCTs are needed to improve the level of evidence.

Acute and continuous exposure of airborne fine particulate matter (PM2.5): diverse outer blood-retinal barrier damages and disease susceptibilities.

BACKGROUND: The association between air pollution and retinal diseases such as age-related macular degeneration (AMD) has been demonstrated, but the pathogenic correlation is unknown. Damage to the outer blood-retinal barrier (oBRB), which consists of the retinal pigment epithelium (RPE) and choriocapillaris, is crucial in the development of fundus diseases. OBJECTIVES: To describe the effects of airborne fine particulate matter (PM2.5) on the oBRB and disease susceptibilities. METHODS: A PM2.5-exposed mice model was established through the administration of eye drops containing PM2.5. Optical coherence tomography angiography, transmission electron microscope, RPE immunofluorescence staining and Western blotting were applied to study the oBRB changes. A co-culture model of ARPE-19 cells with stretching vascular endothelial cells was established to identify the role of choroidal vasodilatation in PM2.5-associated RPE damage. RESULTS: Acute exposure to PM2.5 resulted in choroidal vasodilatation, RPE tight junctions impairment, and ultimately an increased risk of retinal edema in mice. These manifestations are very similar to the pachychoroid disease represented by central serous chorioretinopathy (CSC). After continuous PM2.5 exposure, the damage to the RPE was gradually repaired, but AMD-related early retinal degenerative changes appeared under continuous choroidal inflammation. CONCLUSION: This study reveals oBRB pathological changes under different exposure durations, providing a valuable reference for the prevention of PM2.5-related fundus diseases and public health policy formulation.

Nanosensitizer-mediated augmentation of sonodynamic therapy efficacy and antitumor immunity.

The dense stroma of desmoplastic tumor limits nanotherapeutic penetration and hampers the antitumor immune response. Here, we report a denaturation-and-penetration strategy and the use of tin monosulfide nanoparticles (SnSNPs) as nano-sonosensitizers that can overcome the stromal barrier for the management of desmoplastic triple-negative breast cancer (TNBC). SnSNPs possess a narrow bandgap (1.18 eV), allowing for efficient electron (e-)-hole (h+) pair separation to generate reactive oxygen species under US activation. More importantly, SnSNPs display mild photothermal properties that can in situ denature tumor collagen and facilitate deep penetration into the tumor mass upon near-infrared irradiation. This approach significantly enhances sonodynamic therapy (SDT) by SnSNPs and boosts antitumor immunity. In mouse models of malignant TNBC and hepatocellular carcinoma (HCC), the combination of robust SDT and enhanced cytotoxic T lymphocyte infiltration achieves remarkable anti-tumor efficacy. This study presents an innovative approach to enhance SDT and antitumor immunity using the denaturation-and-penetration strategy, offering a potential combined sono-immunotherapy approach for the cancer nanomedicine field.

Perceived HIV risk and factors associated with condom use among women aged 40 and older: A cross-sectional survey.

Objectives: A noticeable increase in HIV-positive cases among women, particularly those of middle and old age, has been observed worldwide. This study aimed to describe women's perceived HIV risk, HIV/Acquired Immunodeficiency Syndrome (AIDS) knowledge, attitude, and sexual behaviors to determine factors associated with condom use among these women in Hunan, China. Methods: A cross-sectional study was conducted from July 2019 to August 2020 among 958 women aged 40 and older in four regions of Hunan, China. We collected data on sociodemographic characteristics, perceived HIV risk, HIV/AIDS knowledge and attitude, condom use, and sexual behaviors. Univariate and multivariate logistic regression were performed to identify factors related to condom use. Results: Out of 958 participants, 60.6% perceived no risk of HIV infection, and 46.8% reported they had never used a condom during their past sexual life. Those who were older, had lower monthly household income for family, had not received HIV education in the past year, were unwilling to use condoms, could not determine condom use during sexual activity, and had more negative attitudes towards HIV/AIDS and HIV-positive people were less likely to use condoms in their past sexual behaviors. Conclusions: In Hunan Province, most women aged 40 and older perceived themselves as having a low or no risk of HIV infection; their rate of condom use was low, and six factors were associated with condom use. It is imperative to strengthen HIV prevention and control programs among women aged 40 and above, particularly focusing on those who may use condoms infrequently or not at all.

Polymyxin B and fusidic acid, a novel potent synergistic combination against Klebsiella pneumoniae and Escherichia coli isolates with polymyxin B resistance.

The increasing prevalence of multidrug-resistant (MDR) Gram-negative bacteria and comparatively limited options of antibiotics pose a major threat to public health worldwide. Polymyxin B is the last resort against extensively resistant Gram-negative bacterial infections. However, a large number of Gram-negative bacteria exhibited high-level resistance to Polymyxin B, bringing challenges for antimicrobial chemotherapy. Combination therapies using polymyxins and other antibiotics are recommended to treat multidrug-resistant pathogens. In this study, we selected Gram-negative bacterial strains, including Klebsiella pneumoniae and Escherichia coli, to explore whether fusidic acid and polymyxin B have a synergistic killing effect. Through broth microdilution, we observed that minimum inhibitory concentrations (MICs) against polymyxin B in the isolates tested were significantly reduced by the addition of fusidic acid. Notably, chequerboard analysis indicated a synergistic effect between polymyxin B and fusidic acid. In addition, subsequent time-kill experiments showed that the combination of polymyxin B and fusidic acid was more effective than a single drug in killing bacteria. Finally, our investigation utilizing the murine model revealed a higher survival rate in the combination therapy group compared to the monotherapy group. Our research findings provide evidence of the synergistic effect between polymyxin B and fusidic acid. Fusidic acid was shown to increase the sensitivity of multi-drug resistant E. coli and K. pneumoniae to polymyxin B, thereby enhancing its bactericidal activity. This study provides new insights into a potential strategy for overcoming polymyxin B resistance, however, further investigations are required to evaluate their feasibility in real clinical settings.

A novel small-molecule compound S-342-3 effectively inhibits the biofilm formation of Staphylococcus aureus.

IMPORTANCE: Biofilms are an important virulence factor in Staphylococcus aureus and are characterized by a structured microbial community consisting of bacterial cells and a secreted extracellular polymeric matrix. Inhibition of biofilm formation is an effective measure to control S. aureus infection. Here, we have synthesized a small molecule compound S-342-3, which exhibits potent inhibition of biofilm formation in both MRSA and MSSA. Further investigations revealed that S-342-3 exerts inhibitory effects on biofilm formation by reducing the production of polysaccharide intercellular adhesin and preventing bacterial adhesion. Our study has confirmed that the inhibitory effect of S-342-3 on biofilm is achieved by downregulating the expression of genes responsible for biofilm formation. In addition, S-342-3 is non-toxic to Galleria mellonella larvae and A549 cells. Consequently, this study demonstrates the efficacy of a biologically safe compound S-342-3 in inhibiting biofilm formation in S. aureus, thereby providing a promising antibiofilm agent for further research.

Nano-bio interactions in mRNA nanomedicine: Challenges and opportunities for targeted mRNA delivery.

Upon entering the biological milieu, nanomedicines swiftly interact with the surrounding tissue fluid, subsequently being enveloped by a dynamic interplay of biomacromolecules, such as carbohydrates, nucleic acids, and cellular metabolites, but with predominant serum proteins within the biological corona. A notable consequence of the protein corona phenomenon is the unintentional loss of targeting ligands initially designed to direct nanomedicines toward particular cells or organs within the in vivo environment. mRNA nanomedicine displays high demand for specific cell and tissue-targeted delivery to effectively transport mRNA molecules into target cells, where they can exert their therapeutic effects with utmost efficacy. In this review, focusing on the delivery systems and tissue-specific applications, we aim to update the nanomedicine population with the prevailing and still enigmatic paradigm of nano-bio interactions, a formidable hurdle in the pursuit of targeted mRNA delivery. We also elucidate the current impediments faced in mRNA therapeutics and, by contemplating prospective avenues-either to modulate the corona or to adopt an 'ally from adversary' approach-aim to chart a course for advancing mRNA nanomedicine.