Inhibition of HMOX1 by MAFG potentiates the development of depression­like behavior in mice associated with astrocyte-mediated neuroinflammation.

MAF bZIP transcription factor G (MAFG)-driven astrocytes have been reported to promote inflammation in the CNS. However, its function in depression, the primary cause of disability worldwide, has not been well characterized. This study investigated the possible perturbation of heme oxygenase 1 (HMOX1, also known as HO1) by the transcription factor MAFG as an underlying mechanism of the development of depression. The GSE98793 dataset was included for gene expression analysis of whole blood from donors with major depressive disorder and controls, and the target of MAFG was predicted by multiple database mining. Mouse and cellular models of depression were established by chronic unpredictable mild stress (CUMS) and lipopolysaccharide (LPS) treatment of astrocytes, which were treated with lentivirus-encapsulated MAFG and HMOX1 knockdown plasmids. MAFG was highly expressed in the hippocampal tissues of CUMS-challenged mice and LPS-induced astrocytes. MAFG knockdown alleviated depression-like behaviors in mice. MAFG bound to the HMOX1 promoter and repressed its transcription. Knockdown of HMOX1 exacerbated neuroinflammation in astrocytes and accelerated depression-like behavior in mice. In conclusion, MAFG knockdown attenuated CUMS-stimulated depression-like behaviors in mice by astrocyte-mediated neuroinflammation via restoration of HMOX1.

Spectrally engineered textile for radiative cooling against urban heat islands.

Radiative cooling textiles hold promise for achieving personal thermal comfort under increasing global temperature. However, urban areas have heat island effects that largely diminish the effectiveness of cooling textiles as wearable fabrics because they absorb emitted radiation from the ground and nearby buildings. We developed a mid-infrared spectrally selective hierarchical fabric (SSHF) with emissivity greatly dominant in the atmospheric transmission window through molecular design, minimizing the net heat gain from the surroundings. The SSHF features a high solar spectrum reflectivity of 0.97 owing to strong Mie scattering from the nano-micro hybrid fibrous structure. The SSHF is 2.3°C cooler than a solar-reflecting broadband emitter when placed vertically in simulated outdoor urban scenarios during the day and also has excellent wearable properties.

Frontiers and hotspots in hand, foot, and mouth disease research during 2006 to 2023: A bibliometric and visual analysis.

BACKGROUND: Enteroviruses-infected hand, foot, and mouth disease (HFMD) seriously threatens human health. This study aimed to analyze the research status, hotspots, and frontiers of HFMD. METHODS: Publications on HFMD between January 1, 2006, and January 31, 2023, were retrieved from the Web of Science Core database. Bibliometric tools, including CiteSpace, VOSviewer, R package "Bibiometrix," SCImago Graphica, and Charticulator, were utilized to analyze and visualize the data. RESULTS: A total of 1860 articles from 424 journals, involving 8815 authors from 64 countries and 1797 institutions were analyzed. The number of studies on HFMD has shown an increasing trend over the past 18 years, with an annual increase observed since 2006, which is particularly prominent after 2010. Research in this field has centered on the Asian region. Notably, the research hotspots were mainly focused on vaccines, epidemiology, and pathogenesis of HFMD. Among the researchers in this field, Zhang Yong emerged as the most prolific author, while Xu Wenbo had the most significant influence. The Chinese Academy of Sciences was the most productive institution, and China was the most productive country for HFMD research. CONCLUSION: By bibliometric analysis, researchers in the HMFD field can efficiently identify and visually represent their research focus and limitations. In the future, it is crucial to maintain ongoing surveillance of HFMD outbreaks and their pathogenic changes. Additionally, future research should extensively explore the molecular mechanisms underlying Enteroviruses-induced HFMD with a focus on developing vaccines and therapies.

Manuka honey as a non-antibiotic alternative against Staphylococcus spp. and their small colony variant (SCVs) phenotypes.

The antibiotic resistance (ABR) crisis is an urgent global health priority. Staphylococci are among the problematic bacteria contributing to this emergency owing to their recalcitrance to many clinically important antibiotics. Staphylococcal pathogenesis is further complicated by the presence of small colony variants (SCVs), a bacterial subpopulation displaying atypical characteristics including retarded growth, prolific biofilm formation, heightened antibiotic tolerance, and enhanced intracellular persistence. These capabilities severely impede current chemotherapeutics, resulting in chronic infections, poor patient outcomes, and significant economic burden. Tackling ABR requires alternative measures beyond the conventional options that have dominated treatment regimens over the past 8 decades. Non-antibiotic therapies are gaining interest in this arena, including the use of honey, which despite having ancient therapeutic roots has now been reimagined as an alternative treatment beyond just traditional topical use, to include the treatment of an array of difficult-to-treat staphylococcal infections. This literature review focused on Manuka honey (MH) and its efficacy as an anti-staphylococcal treatment. We summarized the studies that have used this product and the technologies employed to study the antibacterial mechanisms that render MH a suitable agent for the management of problematic staphylococcal infections, including those involving staphylococcal SCVs. We also discussed the status of staphylococcal resistance development to MH and other factors that may impact its efficacy as an alternative therapy to help combat ABR.

Association of triglyceride glucose index with stroke: from two large cohort studies and mendelian randomization analysis.

INTRODUCTION: The triglyceride glucose index (TyG) is associated with cardiovascular diseases; however, its association with stroke remains unclear. This study aimed to elucidate this relationship by examining two extensive cohort studies using two-sample Mendelian randomization (MR). METHODS: Using data from the 1999-2018 National Health and Nutrition Examination Survey (NHANES) and the Medical Information Mart for Intensive Care (MIMIC)-IV, the correlation between TyG (continuous and quartile) and stroke was examined using multivariate Cox regression models and sensitivity analyses. Two-sample MR was employed to establish causality between TyG and stroke using the inverse variance weighting method. Genome-wide association study catalog queries were performed for single nucleotide polymorphism-mapped genes, and the STRING platform used to assess protein interactions. Functional annotation and enrichment analyses were also conducted. RESULTS: From the NHANES and MIMIC-IV cohorts, we included 740 and 589 participants with stroke, respectively. After adjusting for covariates, TyG was linearly associated with the risk of stroke death (NHANES: hazard ratio [HR] 0.64, 95% confidence interval [CI]: 0.41-0.99, P=0.047; Q3 vs. Q1, HR 0.62, 95%CI: 0.40-0.96, P=0.033; MIMIC-IV: HR 0.46, 95%CI: 0.27-0.80, P=0.006; Q3 vs. Q1, HR 0.32, 95%CI: 0.12-0.86; Q4 vs. Q1, HR 0.30, 95%CI: 0.10-0.89, P=0.030, P for trend=0.017). Two-sample MR analysis showed genetic prediction supported a causal association between a higher TyG and a reduced risk of stroke (odds ratio 0.711, 95%CI: 0.641-0.788, P=7.64e-11). CONCLUSIONS: TyG was causally associated with a reduced risk of stroke. TyG is a critical factor for stroke risk management.

Development and clinical validation of a dual ddPCR assay for detecting carbapenem-resistant Acinetobacter baumannii in bloodstream infections.

Objective: Acinetobacter baumannii (A. baumannii, AB) represents a major species of Gram-negative bacteria involved in bloodstream infections (BSIs) and shows a high capability of developing antibiotic resistance. Especially, carbapenem-resistant Acinetobacter baumannii (CRAB) becomes more and more prevalent in BSIs. Hence, a rapid and sensitive CRAB detection method is of urgent need to reduce the morbidity and mortality due to CRAB-associated BSIs. Methods: A dual droplet digital PCR (ddPCR) reaction system was designed for detecting the antibiotic resistance gene OXA-23 and AB-specific gene gltA. Then, the specificity of the primers and probes, limit of detection (LOD), linear range, and accuracy of the assay were evaluated. Furthermore, the established assay approach was validated on 37 clinical isolates and compared with blood culture and drug sensitivity tests. Results: The dual ddPCR method established in this study demonstrated strong primer and probe specificity, distinguishing CRAB among 21 common clinical pathogens. The method showed excellent precision (3 × 10-4 ng/µL, CV < 25%) and linearity (OXA-23: y = 1.4558x + 4.0981, R2 = 0.9976; gltA: y = 1.2716x + 3.6092, R2 = 0.9949). While the dual qPCR LOD is 3 × 10-3 ng/µL, the dual ddPCR's LOD stands at 3 × 10-4 ng/µL, indicating a higher sensitivity in the latter. When applied to detect 35 patients with BSIs of AB, the results were consistent with clinical blood culture identification and drug sensitivity tests. Conclusion: The dual ddPCR detection method for OXA-23 and gltA developed in this study exhibits good specificity, excellent linearity, and a higher LOD than qPCR. It demonstrates reproducibility even for minute samples, making it suitable for rapid diagnosis and precision treatment of CRAB in BSIs.

Automated detection of MRI-negative temporal lobe epilepsy with ROI-based morphometric features and machine learning.

Objective: Temporal lobe epilepsy (TLE) predominantly originates from the anteromedial basal region of the temporal lobe, and its prognosis is generally favorable following surgical intervention. However, TLE often appears negative in magnetic resonance imaging (MRI), making it difficult to quantitatively diagnose the condition solely based on clinical symptoms. There is a pressing need for a quantitative, automated method for detecting TLE. Methods: This study employed MRI scans and clinical data from 51 retrospective epilepsy cases, dividing them into two groups: 34 patients in TLE group and 17 patients in non-TLE group. The criteria for defining the TLE group were successful surgical removal of the epileptogenic zone in the temporal lobe and a favorable postoperative prognosis. A standard procedure was used for normalization, brain extraction, tissue segmentation, regional brain partitioning, and cortical reconstruction of T1 structural MRI images. Morphometric features such as gray matter volume, cortical thickness, and surface area were extracted from a total of 20 temporal lobe regions in both hemispheres. Support vector machine (SVM), extreme learning machine (ELM), and cmcRVFL+ classifiers were employed for model training and validated using 10-fold cross-validation. Results: The results demonstrated that employing ELM classifiers in conjunction with specific temporal lobe gray matter volume features led to a better identification of TLE. The classification accuracy was 92.79%, with an area under the curve (AUC) value of 0.8019. Conclusion: The method proposed in this study can significantly assist in the preoperative identification of TLE patients. By employing this method, TLE can be included in surgical criteria, which could alleviate patient symptoms and improve prognosis, thereby bearing substantial clinical significance.

Association between triglyceride glucose index and all-cause mortality in patients with cerebrovascular disease: a retrospective study.

BACKGROUND: Triglyceride glucose (TyG) is associated with stroke, atherosclerosis, and adverse clinical outcomes. However, its correlation with cerebrovascular disease (CVD) mortality remains unclear. This study aimed to investigate the relationship between TyG index and mortality in patients with CVD. METHODS: Patient data sourced from the Medical Information Mart for Intensive Care -IV database were categorized based on TyG quartiles. Kaplan-Meier survival analysis was used to estimate survival disparities among the TyG subgroups. Cox proportional risk modeling was used to examine the association between the TyG index and mortality. Generalized summation models were applied to fit the smoothed curves. log-likelihood ratio test were used to analyze the non-linear relationship. RESULTS: The study comprised 1,965 patients (50.18% were male). The 28-day and 90-day mortality rates were 20.10% and 24.48%, respectively. The TyG index exhibited a linear relationship with the 28-day mortality (Hazards ratio (HR), 1.16; 95% confidence interval (CI), 0.99-1.36) and the 90-day mortality (HR, 1.18; 95% CI, 1.02-1.37). In the TyG Q4 group, each 1 mg/dl increase was linked to a 35% rise in the risk of 28-day mortality and a 38% increase in the risk of 90-day mortality. Subgroup analyses highlighted a more substantial association between TyG index and 90-day mortality in the diabetic group. CONCLUSION: Our findings underscore the positive association between TyG and the 28- and 90-day mortality rates in patients with CVD. This insight may prove pivotal for identifying at-risk populations and enhancing risk prediction in the clinical management of CVD.

TBC1D1 represses glioma progression by altering the integrity of the cytoskeleton.

BACKGROUND: Glioma is one of the most aggressive malignant brain tumors and is characterized by invasive growth and poor prognosis. TBC1D1, a member of the TBC family, is associated with the development of various malignancies. However, the role of TBC1D1 in glioma-genesis remains unclear. METHODS: The effect of TBC1D1 on the prognosis of glioma patients and related influencing factors were analyzed in the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. Expression of TBC1D1 in glioma cell lines was detected by western blotting. Cell viability and proliferation were measured by EdU and Colony formation assays, respectively. Transwell and wound healing assays were performed to determine the cell migration and invasion capacities. Immunofluorescence was used to observe actin morphology in the cytoskeleton. RESULTS: We discovered that high TBC1D1 expression in gliomas led to poor prognosis. Downregulation of TBC1D1 in glioma cells significantly inhibited multiple important functions, such as proliferation, migration, and invasion. We further demonstrated that the tumor-inhibitory effect of TBC1D1 might occur through the P-LIMK/cofilin pathway, destroying the cytoskeletal structure and affecting the depolymerization of F-actin, thereby inhibiting glioma migration. CONCLUSION: TBC1D1 affects the balance and integrity of the actin cytoskeleton via cofilin, thereby altering the morphology and aggressiveness of glioma cells. This study provides a new perspective on its role in tumorigenesis, thereby identifying a potential therapeutic target for the treatment of gliomas.

MSWIFA and cement cooperate in the disposal of soft soil - experimental study on silty sand and silty clay.

Municipal solid waste incineration fly ash (MSWIFA) can be reused as a positive additive to strengthen soft soil. In this study, MSWIFA was initially used as a supplementary solidification material in combination with ordinary Portland cement to prepare fly ash cement-stabilized soil (FACS) with silty sand and silty clay, respectively. The ratio of MWSIFA to total mass was 5%, 10%, and 15%, and the cement content was set as 10% and 15%. The mechanical properties of FACS were evaluated by unconfined compressive strength test. The heavy metal-leaching test was conducted to estimate the environmental risk of FACS. The scanning electron microscope was used to test the micro-structure of FACS. The X-ray diffraction was performed to analyze material composition of FACS. The result indicates that the collaborative solidification of soft soil with MSWIFA and cement is feasible. Regarding the silty clay, the FA had positive effects on the silty clay in the service age (between 50 and 100% with 15% MSWIFA), as the MSWIFA reformulated the initial silty clay structure, resulting in interconnection and pore fill between particles. It can be founded that C-S-H and ettringite are the main products of MSWIFA and cement hydration, which are formed by the hydration of C3S and C2S. Regarding the silty sand, the MSWIFA decreased the peak strength (between 35 and 48% with 15% MSWIFA) but increased the ductility of the stabilized cement. Under the same mix proportions, the leaching toxicities of Zn and Pb in FACS of silty clay were obviously lower than were those of silty sand. Generally, the leaching concentrations of tested metals under all the mix proportions were well below the limit value set by GB 18598-2019 for hazardous waste landfill. Thus, the reuse of MSWIFA in cement-stabilized soil would be one of the effective methods in soft soil treatment and solid waste reduction.

CAFs Homologous Biomimetic Liposome Bearing BET Inhibitor and Pirfenidone Synergistically Promoting Antitumor Efficacy in Pancreatic Ductal Adenocarcinoma.

BRD4 is a member of the BET protein family involved in chromatin remodeling and transcriptional regulation. Several BET inhibitors (BETi) have entered clinical trials, demonstrating potential in inducing cancer cell apoptosis and tumor regression. However, resistance to BETi is common in solid tumors. In pancreatic cancer, it is found that cancer-associated fibroblasts (CAFs) in the tumor microenvironment reduce the BET inhibitor JQ1 sensitivity by inducing BRD4 expression. Moreover, CAFs play a crucial role in the formation of a dense stromal barrier. Therefore, targeting CAFs in the tumor microenvironment of pancreatic cancer not only enhances cancer cells sensitivity to JQ1 but also increases drug perfusion and improves oxygen supply, thus reducing glycolysis and limiting energy supply. To address this challenge, a homologous targeting mechanism utilizing activated fibroblast membrane-coated liposomes is proposed for specific drug precise target to CAFs-rich pancreatic cancer. Additionally, TAT peptides enable liposomes penetration, delivering PFD for targeted anti-fibrotic therapy, reducing extracellular matrix generation and glycolysis, and enhancing JQ1 delivery and sensitivity. In conclusion, the findings indicate the tremendous potential of this CAFs-targeting liposomal delivery system in pancreatic cancer.

Preparation and efficacy verification of three-dimensional printed partitioned multi-effect precision-care gel facial mask.

OBJECTIVE: A partition multi-effect precision-care gel facial mask conforming to facial skin characteristics was prepared using three-dimensional (3D) printing technology. METHODS: First, the hydrogel matrix and humectant of a 3D-printed gel for facial masks were screened, and three 3D-printed gels of arbutin, hexapeptide, and salicylic acid were prepared with whitening, wrinkle removal, and oil control functions, respectively. Skin irritation tests were performed on the gels. Physicochemical properties such as pH, heat and cold tolerance were evaluated. The efficacy of three 3D-printed gels was assessed by measuring melanin value, wrinkle depression score, and oil secretion. Finally, the facial mask model design and printing parameters were studied, and a partition multi-effect precision-care gel facial mask was printed in line with facial skin characteristics. RESULTS: For the 3D-printed facial mask, the gel prescription with 2% hydroxyethyl cellulose gel as matrix and 7% glycerol as humectant was the best. The prepared 3D-printed gel did not irritate the human skin, and its physicochemical properties met the Chinese facial mask industry standard (QB/T2872-2017). We showed that three types of 3D-printed gels containing arbutin, hexapeptide, and salicylic acid could be applied to the corresponding parts of the face to solve different problems, such as facial skin dullness, wrinkles, and oil secretion. Therefore, according to facial physiological characteristics, the facial mask model was designed for the forehead and nasolabial fold, which needs to be anti-wrinkled; the cheek, which needs to be whitened; and the nose and chin, which need oil control. The optimal printing parameters were 0.26 mm nozzle diameter, 90 mm/s printing speed, 30% filling density, 140% wire extrusion ratio, and 0.25 mm layer height. Different skin care effects can be achieved using a three-nozzle printer to print arbutin, hexapeptide, or salicylic acid gel on the mask's forehead and nasolabial fold, cheek, and nose and chin, respectively. CONCLUSION: The 3D-printed partition multi-effect care gel facial mask prepared according to the skin features of different parts of the face can overcome the problem of the single skincare effect of the mass-produced facial masks.

OBJECTIF: Un masque facial de soin de précision en gel à effets multiples, adapté aux caractéristiques de la peau du visage, a été préparé à l'aide de la technologie d'impression tridimensionnelle (3D). MÉTHODES: Tout d'abord, la matrice d'hydrogel et l'humectant d'un gel imprimé en 3D pour les masques faciaux ont été sélectionnés, et trois gels imprimés en 3D d'arbutine, d'hexapeptide et d'acide salicylique ont été préparés avec des fonctions de blanchiment, d'élimination des rides et de contrôle du sébum, respectivement. Des tests d'irritation cutanée ont été réalisés sur les gels. Les propriétés physicochimiques telles que le pH et la tolérance à la chaleur et au froid ont été évaluées. L'efficacité des trois gels imprimés en 3D a été évaluée en mesurant la valeur de la mélanine, le score de dépression des rides et la sécrétion de sébum. Enfin, la conception du modèle de masque facial et les paramètres d'impression ont été étudiés, et un masque facial de gel de soin de précision à effets multiples a été imprimé en fonction des caractéristiques de la peau du visage. RÉSULTATS: Pour le masque facial imprimé en 3D, la prescription de gel avec 2 % de gel d'hydroxyéthylcellulose comme matrice et 7 % de glycérol comme humectant était la meilleure. Le gel imprimé en 3D n'a pas irrité la peau humaine et ses propriétés physicochimiques sont conformes à la norme industrielle chinoise relative aux masques faciaux (QB/T2872­2017). Nous avons montré que trois types de gels imprimés en 3D contenant de l'arbutine, de l'hexapeptide et de l'acide salicylique pouvaient être appliqués aux parties correspondantes du visage pour résoudre différents problèmes, tels que l'aspect terne de la peau du visage, les rides et la sécrétion de sébum. Par conséquent, en fonction des caractéristiques physiologiques du visage, le modèle de masque facial a été conçu pour le front et le sillon nasogénien, qui doivent être antirides, la joue, qui doit être blanchie, et le nez et le menton, qui ont besoin d'un contrôle du sébum. Les paramètres d'impression optimaux étaient les suivants : diamètre de buse de 0,26 mm, vitesse d'impression de 90 mm/s, densité de remplissage de 30 %, rapport d'extrusion du fil de 140 % et hauteur de couche de 0,25 mm. Différents effets de soin de la peau peuvent être obtenus en utilisant une imprimante à trois buses pour imprimer de l'arbutine, de l'hexapeptide ou du gel d'acide salicylique sur le front et le sillon nasogénien, la joue, le nez et le menton du masque, respectivement. CONCLUSION: Le masque facial en gel de soin à effets multiples imprimé en 3D et préparé en fonction des caractéristiques de la peau des différentes parties du visage peut résoudre le problème de l'effet de soin unique des masques faciaux produits en masse.

Cold atmospheric plasma-enabled platelet vesicle incorporated iron oxide nano-propellers for thrombolysis.

A new approach to treating vascular blockages has been developed to overcome the limitations of current thrombolytic therapies. This approach involves biosafety and multimodal plasma-derived theranostic platelet vesicle incorporating iron oxide constructed nano-propellers platformed technology that possesses fluorescent and magnetic features and manifold thrombus targeting modes. The platform is capable of being guided and visualized remotely to specifically target thrombi, and it can be activated using near-infrared phototherapy along with an actuated magnet for magnetotherapy. In a murine model of thrombus lesion, this proposed multimodal approach showed an approximately 80 % reduction in thrombus residues. Moreover, the new strategy not only improves thrombolysis but also boosts the rate of lysis, making it a promising candidate for time-sensitive thrombolytic therapy.

PFKP confers chemoresistance by upregulating ABCC2 transporter in non-small cell lung cancer.

Background: Chemoresistance is a significant factor contributing to tumor recurrence and treatment failure in non-small cell lung cancer (NSCLC). The phosphofructokinase, platelet (PFKP) is highly expressed in NSCLC and is associated with a poor prognosis. Exploring the molecular mechanism and identifying effective strategies to overcome chemoresistance will have important clinical significance in improving the diagnosis and treatment of NSCLC. Methods: The correlation between PFKP and cisplatin resistance in NSCLC patients was assessed by organoids and immunohistochemistry. The impact of PFKP on the prognosis of NSCLC patients was analyzed using The Cancer Genome Atlas (TCGA) database. In NSCLC cell lines, the expression of PFKP was modulated using lentivirus, and cisplatin sensitivity was assessed by flow cytometry. Subsequently, the therapeutic effect of cisplatin was tested in BALB/c nude mice implanted subcutaneously with tumor cells. We performed luciferase assay and immunohistochemistry (IHC) to investigate the correlation between PFKP and ABCC2 (ATP-binding cassette sub-family C member 2). Results: Overexpression of PFKP was correlated with poorer survival rates in NSCLC patients who received platinum-based chemotherapy. Using NSCLC organoid, we found that the expression of PFKP was elevated in cisplatin (CDDP)-resistant patients with NSCLC. Overexpression of PFKP decreased the sensitivity of NSCLC cells to CDDP, while genetic inhibition of PFKP enhanced CDDP sensitivity both in vitro and in vivo. Furthermore, we found that PFKP upregulated ABCC2 by increasing the levels of phosphorylation of IκBα and nuclear p65 NF-κB subunit protein. Conclusions: PFKP can regulate the expression of ABCC2 through the activation of NF-κB, which in turn promotes chemoresistance in NSCLC. PFKP has the potential to be a personalized therapeutic target for NSCLC patients with chemoresistance.

Combinatorial efficacy of Manuka honey and antibiotics in the in vitro control of staphylococci and their small colony variants.

Introduction: Staphylococci are among the list of problematic bacteria contributing to the global antibiotic resistance (ABR) crisis. Their ability to adopt the small colony variant (SCV) phenotype, induced by prolonged antibiotic chemotherapy, complicates staphylococcal infection control options. Novel and alternative approaches are needed to tackle staphylococcal infections and curb ABR. Manuka honey (MH), a non-antibiotic alternative is recognized for its unique antibacterial activity based on its methylglyoxal (MGO) component. Methods: In this study, MH (MGO 830+) was tested in combination with gentamicin (GEN), rifampicin (RIF), or vancomycin (VA) against staphylococcal wildtype (WT) and SCVs. To our knowledge, there are no current studies in the literature documenting the effects of MH on staphylococcal SCVs. While Staphylococcus aureus is well-studied for its international ABR burden, limited data exists demonstrating the effects of MH on S. epidermidis and S. lugdunensis whose pathogenic relevance and contribution to ABR is also rising. Results & discussion: The three staphylococci were most susceptible to RIF (0.06-0.24 µg/ml), then GEN (0.12-0.49 µg/ml), and lastly VA (0.49-0.96 µg/ml). The MICs of MH were 7%, 7-8%, and 6-7% (w/v), respectively. Fractional inhibitory concentration (FIC) evaluations showed that the combined MH + antibiotic effect was either additive (FICI 1-2), or partially synergistic (FICI >0.5-1). While all three antibiotics induced SCVs in vitro, stable SCVs were observed in GEN treatments only. The addition of MH to these GEN-SCV-induction analyses resulted in complete suppression of SCVs (p<0.001) in all three staphylococci, suggesting that MH's antibacterial properties interfered with GEN's SCV induction mechanisms. Moreover, the addition of MH to growth cultures of recovered stable SCVs resulted in the inhibition of SCV growth by at least 99%, indicating MH's ability to prevent subsequent SCV growth. These in vitro analyses demonstrated MH's broad-spectrum capabilities not only in improving WT staphylococci susceptibility to the three antibiotics, but also mitigated the development and subsequent growth of their SCV phenotypes. MH in combination with antibiotics has the potential to not only resensitize staphylococci to antibiotics and consequently require less antibiotic usage, but in instances where prolonged chemotherapy is employed, the development and growth of SCVs would be hampered, providing a better clinical outcome, all of which mitigate ABR.

Lithium chloride induces apoptosis by activating endoplasmic reticulum stress in pancreatic cancer.

Lithium compounds, a classic class of metal complex medicine that target GSK 3ß and are widely known as mood-stabilizer, have recently been reported as potential anti-tumor drugs. The objective of this investigation was to explore the anticancer potential of lithium chloride (LiCl) and elucidate its mode of action in pancreatic cancer cells. The MTT, colony formation, and Edu assay were used to evaluate the impact of LiCl on pancreatic cancer cell proliferation. Various methods were employed to investigate the anti-tumor activity of LiCl and its underlying mechanisms. Cell cycle analysis and apoptosis detection assays were utilized for in vitro experiments, while the orthotopic pancreatic cancer mouse model was employed to evaluate the effectiveness of LiCl treatment in vivo. Furthermore, the impact of LiCl on the proliferation of patient-derived organoids was also studied. The results demonstrated that LiCl inhibited the proliferation of pancreatic cancer (PC) cells, induced G2/M phase arrest, and activated apoptosis. Notably, the triggering of endoplasmic reticulum (ER) stress by LiCl was observed, leading to the activation of the PERK/CHOP/GADD34 pathway, which subsequently promoted apoptosis in PC cells. In the future, Lithium compounds could become an essential adjunct in the treatment of human pancreatic cancer.

A Novel 1000 MPa Grade Ultrafine-Grained Dual-Phase Press Hardening Steel with Superior Oxidation Resistance and High Ductility.

1000 MPa grade low-carbon martensite press hardening steels (PHS) are widely used in energy-absorbing domains of automotive parts, such as the bottom of a B-pillar. To prevent oxide scale formation during hot forming, this PHS is often required to be protected by an additional Al-Si coating. In addition, although the low carbon martensitic microstructure grants it excellent bending toughness, the ductility tends to be limited. In this study, a novel 1000 MPa grade ultrafine-grained (UFG) martensite-ferrite (F-M) dual-phase (DP) PHS with superior oxidation resistance was designed using tailored additions of Cr, Mn, and Si, and refining the initial microstructure. Only 0.55 ± 0.18 µm thick oxide film is formed in the designed steel during austenitizing heating and stamping, which is significantly lower than the 24.6 ± 3.1 µm thick oxide film formed in conventional 1000 MPa grade low-carbon martensite PHS under the identical condition. The superior oxidation resistance of designed steel can be attributed to the rapid formation of the protective Si-rich, Cr-rich, and Mn-rich oxide layers during annealing. Moreover, due to the presence of ferrite and ultrafine microstructure, the designed steel also shows a significant improvement in ductility from 8.5% to 16.8% without sacrificing strength and bending toughness compared with conventional 1000 MPa grade low-carbon martensite PHS.

SLC1A5 is a novel biomarker associated with ferroptosis and the tumor microenvironment: a pancancer analysis.

Solute carrier family 1 member 5 (SLC1A5) is a member of the solute carrier (SLC) superfamily of transporters and plays an important role in tumors as a key transporter of glutamine into cells. However, the relationship between SLC1A5, which is involved in immune regulation, and immune cell infiltration in the tumor microenvironment has not been elucidated, and the relationship between SLC1A5 and ferroptosis is rarely reported. Therefore, we comprehensively analyzed the expression level of SLC1A5 across cancers and compared it with that in normal tissues. Then, the relationship between SLC1A5 expression and the tumor immune microenvironment was analyzed by single-cell analysis, gene set enrichment analysis (GSEA), and Tumor Immune Estimation Resource (TIMER). Next, the correlations of the SLC1A5 expression level with immunotherapy response, immunomodulator expression, tumor mutation burden (TMB) and microsatellite instability (MSI) were evaluated. Finally, in vitro experiments verified that SLC1A5 participates in ferroptosis of glioma cells to regulate tumor progression. Our results indicated that SLC1A5 is aberrantly expressed in most cancer types and closely associated with prognosis. The GSEA results showed that SLC1A5 is involved in immune activation processes and closely related to the infiltration levels of different immune cells in different cancer types. Upon further investigation, we found that SLC1A5 is a suppressor of ferroptosis in glioma, and SLC1A5 knockdown inhibited the proliferation and migration of glioma cells in vitro. In conclusion, we conducted a pancancer analysis of SLC1A5, demonstrated its role as a prognostic biomarker in cancer patients and explored its potential biological functions.

Artificial intelligence and bioinformatics analyze markers of children's transcriptional genome to predict autism spectrum disorder.

Introduction: Autism spectrum disorder (ASD), characterized by difficulties in social interaction and communication as well as restricted interests and repetitive behaviors, is extremely challenging to diagnose in toddlers. Early diagnosis and intervention are crucial however. Methods: In this study, we developed a machine learning classification model based on mRNA expression data from the peripheral blood of 128 toddlers with ASD and 126 controls. Differentially expressed genes (DEGs) between ASD and controls were identified. Results: We identified genes such as UBE4B, SPATA2 and RBM3 as DEGs, mainly involved in immune-related pathways. 21 genes were screened as key biomarkers using LASSO regression, yielding an accuracy of 86%. A neural network model based on these 21 genes achieved an AUC of 0.88. Discussion: Our findings suggest that the identified neurotransmitters and 21 immune-related biomarkers may facilitate the early diagnosis of ASD. The mRNA expression profile sheds light on the biological underpinnings of ASD in toddlers and potential biomarkers for early identification. Nevertheless, larger samples are needed to validate these biomarkers.

Plasma-Derived Nanoclusters for Site-Specific Multimodality Photo/Magnetic Thrombus Theranostics.

Traditional thrombolytic therapeutics for vascular blockage are affected by their limited penetration into thrombi, associated off-target side effects, and low bioavailability, leading to insufficient thrombolytic efficacy. It is hypothesized that these limitations can be overcome by the precisely controlled and targeted delivery of thrombolytic therapeutics. A theranostic platform is developed that is biocompatible, fluorescent, magnetic, and well-characterized, with multiple targeting modes. This multimodal theranostic system can be remotely visualized and magnetically guided toward thrombi, noninvasively irradiated by near-infrared (NIR) phototherapies, and remotely activated by actuated magnets for additional mechanical therapy. Magnetic guidance can also improve the penetration of nanomedicines into thrombi. In a mouse model of thrombosis, the thrombosis residues are reduced by ≈80% and with no risk of side effects or of secondary embolization. This strategy not only enables the progression of thrombolysis but also accelerates the lysis rate, thereby facilitating its prospective use in time-critical thrombolytic treatment.