Outcomes, responses, and prognostic analyses of intrathecal combined treatment for leptomeningeal metastasis from lung adenocarcinoma.

BACKGROUND: Leptomeningeal metastasis (LM) is a severe lung cancer complication, with potentially fatal consequences. The use of intrathecal therapy (IT) combined with systemic therapy has shown promise as a treatment approach for LM. Thus, this study aimed to evaluate the features and responses to IT combined therapy and identify determinants affecting patients with leptomeningeal metastasis resulting from lung adenocarcinoma (LM-LA). METHODS: A retrospective analysis of medical records from our hospital database was performed, covering from April 2018 to August 2022, for 37 patients diagnosed with LM-LA and treated with IT combined therapy. Patients who received IT combined therapy for LM-LA were evaluated for demographic characteristics, treatment efficacy, survival, and variables that impacted them. RESULTS: The median overall survival (mOS) of 37 patients was 16.0 months, and the survival rates at 6 and 12 months were 75.7% and 35.1%, respectively. Among the 21 patients with LM-LA who received IT combined with tyrosine kinase inhibitors (TKIs), the mOS was 17.0 months, which was significantly longer than that of patients treated with IT combined with chemotherapy (7.0 months, P = 0.010) and the best supportive care (6.0 months, P = 0.001). However, no significant survival benefit was observed in patients treated with IT combined with TKIs when compared with those treated with IT combined with PD-1 (5.0 months, P = 0.249). Multivariate analysis indicated that the combination of TKIs was an independent favorable prognostic factor for patients with LM-LA. CONCLUSION: Combination treatment is regarded as an additional option for patients with LM-LA. Compared with other combination therapies in our study, IT combined with TKI therapy provided a better survival outcome for patients with LM-LA.

Preoperative supine time for adrenal venous sampling: a prospective randomized controlled trial.

BACKGROUND: Primary aldosteronism (P.A.) is the most common form of secondary hypertension, accounting for 5% of hypertensive patients and 17-23% of patients with resistant hypertension. Compared to primary hypertension, P.A. is more prone to cause severe organ damage and even early death. Adrenal venous sampling (AVS) is a practical confirmatory test for subtyping aldosterone-producing adenoma and bilateral adrenal hyperplasia, helping physicians to make an accurate decision between surgery or medication. According to guidelines, supine in bed before AVS is recommended for a desirable result of AVS. However, investigations about the most optimal preoperative supine time before AVS are lacking. METHODS/DESIGN: This is a multi-center prospective randomized controlled study. One hundred twenty patients diagnosed as P.A. and willing for AVS examination will be included. Participants will be randomly allocated to a 15-min supine time group or 2-h supine time group. The primary outcome is the degree of biochemical remission (serum potassium and orthostatic ARR). The secondary outcomes are degrees of clinical remission (blood pressure, type and dose of antihypertensive drugs), the technical success rate, and the adverse event of AVS (selective index ≥ 2 is considered successful surgery without corticotropin stimulation). DISCUSSION: P.A. is an intractable public health problem, and many techniques including AVS have been developed to identify this disease correctly. This study will help to understand whether the length of preoperative supine time would affect the diagnostic efficacy of AVS and thus help to formulate a more reasonable AVS procedure. TRIAL REGISTRATION: ClinicalTrials.gov NCT05658705. Registered on 10 September 2022.

Double-edged effect of frequent freeze-thaw on the stability of zero-valent iron after heavy metal remediation.

Freeze-thaw cycles (FTCs) cause dynamic microscale changes in ions and solvents. During freezing, heavy metals adsorbed on zero-valent iron (M-ZVI) and protons are excluded by ice crystals and concentrated in the liquid-like grain boundary region. The high proton concentration in this region leads to the dissolution of the passivation layer of ZVI. To assess the environmental risks of M-ZVI during FTCs, this study evaluated the stability of M-ZVI in this scenario from both microscale and macroscale perspectives. The results showed that the dissolution of the passivation layer had a dual effect on the stability of M-ZVI, which depends on the by-products of M-ZVI. The dissolution of the passivation layer was accompanied by the leaching of heavy metals, such as Ni-ZVI, but it also enhanced the reactivity of ZVI, causing it to re-react with desorbed heavy metals. The stability of Cr-ZVI and Cd-ZVI was improved due to frequent FTCs. Furthermore, changes in the surrounding environment (water dipole moment, ion concentration, etc.) of ZVI affected the crystallization of Fe oxides, increasing the content of amorphous Fe oxide. As low-crystallinity Fe oxides could facilitate ion doping, Ni2+ was doped into Fe3O4 lattice during FTCs, which reduced the mobility of heavy metals. Contrary to traditional views that freezing temperatures slow chemical reactions, this study provides new insights into the application of iron-based materials in cold environments.

Target-Site and Metabolic Resistance Mechanisms to Penoxsulam in Late Watergrass (Echinochloa phyllopogon) in China.

Echinochloa phyllopogon, a malignant weed in Northeast China's paddy fields, is currently presenting escalating resistance concerns. Our study centered on the HJHL-715 E. phyllopogon population, which showed heightened resistance to penoxsulam, through a whole-plant bioassay. Pretreatment with a P450 inhibitor malathion significantly increased penoxsulam sensitivity in resistant plants. In order to determine the resistance mechanism of the resistant population, we purified the resistant population from individual plants and isolated target-site resistance (TSR) and nontarget-site resistance (NTSR) materials. Pro-197-Thr and Trp-574-Leu mutations in acetolactate synthase (ALS) 1 and ALS2 of the resistant population drove reduced sensitivity of penoxsulam to the target-site ALS, the primary resistance mechanisms. To fully understand the NTSR mechanism, NTSR materials were investigated by using RNA-sequencing (RNA-seq) combined with a reference genome. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis further supported the enhanced penoxsulam metabolism in NTSR materials. Gene expression data and quantitative reverse transcription polymerase chain reaction (qRT-PCR) validation confirmed 29 overexpressed genes under penoxsulam treatment, with 16 genes concurrently upregulated with quinclorac and metamifop treatment. Overall, our study confirmed coexisting TSR and NTSR mechanisms in E. phyllopogon's resistance to ALS inhibitors.

Comprehensive bioinformatics analysis revealed potential key genes and pathways underlying abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a permanent, asymptomatic segmental dilatation of the abdominal aorta, with a high mortality risk upon rupture. Identification of potential key genes and pathways may help to develop curative drugs for AAA. We conducted RNA-seq on abdominal aortic tissues from both AAA patients and normal individuals as a control group. Integrated bioinformatic analysis was subsequently performed to comprehensively reveal potential key genes and pathways. A total of 1148 differential expressed genes (DEGs) (631 up-regulated and 517 down-regulated) were identified in our study. Gene Ontology (GO) analysis revealed enrichment in terms related to extracellular matrix organization, while KEGG analysis indicated enrichment in hematopoietic cell lineage and ECM-receptor interaction. Protein-protein interaction (PPI) network analysis revealed several candidate key genes, and differential expression of 6 key genes (CXCL8, CCL2, PTGS2, SELL, CCR7, and CXCL1) was validated by Gene Expression Omnibus (GEO) datasets. Receiver operating characteristic curve (ROC) analysis demonstrated these genes' high discriminatory ability between AAA and normal tissues. Immunohistochemistry indicated that several key genes were highly expressed in AAA tissues. Single-cell RNA sequencing revealed differential distribution patterns of these identified key genes among various cell types. 26 potential drugs linked to our key genes were found through DGIdb. Overall, our study provides a comprehensive evaluation of potential key genes and pathways in AAA, which could pave the way for the development of curative pharmacological therapies.

Warburg effect-related risk scoring model to assess clinical significance and immunity characteristics of glioblastoma.

BACKGROUND: Glioblastoma (GBM), the most common primary malignant brain tumor, has a poor prognosis, with a median survival of only 14.6 months. The Warburg effect is an abnormal energy metabolism, which is the main cause of the acidic tumor microenvironment. This study explored the role of the Warburg effect in the prognosis and immune microenvironment of GBM. METHODS: A prognostic risk score model of Warburg effect-related genes (Warburg effect signature) was constructed using GBM cohort data from The Cancer Genome Atlas. Cox analysis was performed to identify independent prognostic factors. Next, the nomogram was built to predict the prognosis for GBM patients. Finally, the drug sensitivity analysis was utilized to find the drugs that specifically target Warburg effect-related genes. RESULTS: Age, radiotherapy, chemotherapy, and WRGs score were confirmed as independent prognostic factors for GBM by Cox analyses. The C-index (0.633 for the training set and 0.696 for the validation set) and area under curve (>0.7) indicated that the nomogram exhibited excellent performance. The calibration curve also indicates excellent consistency of the nomogram between predictions and actual observations. In addition, immune microenvironment analysis revealed that patients with high WRGs scores had high immunosuppressive scores, a high abundance of immunosuppressive cells, and a low response to immunotherapy. The Cell Counting Kit-8 assays showed that the drugs targeting Warburg effect-related genes could inhibit the GBM cells growth in vitro. CONCLUSION: Our research showed that the Warburg effect is connected with the prognosis and immune microenvironment of GBM. Therefore, targeting Warburg effect-related genes may provide novel therapeutic options.

Current status and prospects of MOFs in controlled delivery of Pt anticancer drugs.

Cancer has become the second leading reason for death in the world. Still, cancer therapy development is exceptionally challenging because the tumor microenvironment is very complex, and individual tumors are very different. In recent years, researchers have found that platinum-based drugs in the form of metal complexes can effectively solve tumor resistance. In this regard, metal-organic frameworks (MOFs) as suitable carriers with high porosity are also exceptional in the biomedical field. Therefore, this article reviews the application of platinum as an anticancer drug and the composite anticancer properties of platinum and MOF materials and prospects for its future development, which provides a new direction for further research in the biomedical field.

The influence of various microplastics on PBDEs contaminated soil remediation by nZVI and sulfide-nZVI: Impedance, electron-accepting/-donating capacity and aging.

The microplastics (MPs) existed in the environment widely has resulted in novel thinking about in-situ remediation techniques, such as nano-zero-valent iron (nZVI) and sulfided nZVI (S-nZVI), which were often compromised by various environmental factors. In this study, three common MPs such as polyvinyl chloride (PVC), polystyrene (PS), and polypropylene (PP) in soil were found to inhibit the degradation rate of decabromodiphenyl ether (BDE209) by nZVI and S-nZVI to different degrees due to MPs inhibiting of electron transfer which is the main way to degrade BDE209. The inhibition strength was related to its impedance (Z) and electron-accepting (EAC)/-donating capacity (EDC). Based on the explanation of the inhibition mechanism, the reason for different aging degrees of nZVI and S-nZVI in different MPs was illustrated, especially in PVC systems. Furthermore, the aging of reacted MPs, functionalization and fragmentation in particular, indicated that they were involved in the degradation process. Moreover, this work provided new insights into the field application of nZVI-based materials for removing persistent organic pollutants (POPs).

Signaling pathways in brain tumors and therapeutic interventions.

Brain tumors, although rare, contribute to distinct mortality and morbidity at all ages. Although there are few therapeutic options for brain tumors, enhanced biological understanding and unexampled innovations in targeted therapies and immunotherapies have considerably improved patients' prognoses. Nonetheless, the reduced response rates and unavoidable drug resistance of currently available treatment approaches have become a barrier to further improvement in brain tumor (glioma, meningioma, CNS germ cell tumors, and CNS lymphoma) treatment. Previous literature data revealed that several different signaling pathways are dysregulated in brain tumor. Importantly, a better understanding of targeting signaling pathways that influences malignant behavior of brain tumor cells might open the way for the development of novel targeted therapies. Thus, there is an urgent need for a more comprehensive understanding of the pathogenesis of these brain tumors, which might result in greater progress in therapeutic approaches. This paper began with a brief description of the epidemiology, incidence, risk factors, as well as survival of brain tumors. Next, the major signaling pathways underlying these brain tumors' pathogenesis and current progress in therapies, including clinical trials, targeted therapies, immunotherapies, and system therapies, have been systemically reviewed and discussed. Finally, future perspective and challenges of development of novel therapeutic strategies in brain tumor were emphasized.

Decellularized brain extracellular matrix slice glioblastoma culture model recapitulates the interaction between cells and the extracellular matrix without a nutrient-oxygen gradient interference.

Decellularized extracellular matrix (dECM) is a valuable tool for generating three-dimensional in vitro tumor models that effectively recapitulate tumor-extracellular matrix (ECM) interactions. However, in current culture models, the components and structures of dECM are enzymatically disrupted to form hydrogels, making it difficult to recapitulate the native ECM. Additionally, when studying ECM-cell interactions, large-volume tumor culture models are incompatible with traditional experimental techniques and the nutrient-oxygen concentration gradient, which is a significant confounding factor. To address these issues, we developed a decellularized brain extracellular matrix slice (dBECMS) glioblastoma (GBM) culture model. This model possesses good light transmittance and substance diffusivity, making it compatible with traditional experimental techniques without forming nutrient-oxygen concentration gradients. Through transcriptomic analysis, we found that native brain ECM has a broad impact on glioma cells; the impact involves the ECM-ECM receptor interactions and the ECM and metabolic reprogramming. Further experiments demonstrated that dBECMS promoted glucose consumption and lactate production in GBM cells. Silver staining experiments revealed abundant proteins in the media of dBECMS, suggesting the degradation of the brain ECM by GBM cells. Transcriptome analysis also showed that the dBECMS-GBM culture model more accurately recapitulated the transcriptional profile of GBM than the two-dimensional culture. We experimentally demonstrated that the dBECMS-GBM model enhanced the resistance of GBM cells to temozolomide and increased the stemness of GBM cells. Additionally, we demonstrated the feasibility of the dBECMS-GBM model as a platform for drug response modeling. STATEMENT OF SIGNIFICANCE: The decellularized brain extracellular matrix (ECM) slice glioblastoma culture model mimics the interaction between native brain ECM and glioblastoma when glioblastoma infiltrates the brain and reveals the effects of native brain ECM on glioblastoma metabolism, ECM reprogramming, drug responsiveness, and stemness.

Effect of calcination temperatures on the performance of rectorite for cadmium immobilization in soil: Freeze-thaw, plant growth, and microbial diversity.

The immobilization of cadmium (Cd(II)) in soil using calcined rectorite (REC) was investigated in this research. The results of immobilization show that a small amount of REC calcined at 700 °C (REC-700 °C) could effectively immobilize 90% of Cd(II) in soil, while the immobilization efficiency of REC only reached 42%. Moreover, the immobilization efficiency of REC calcined at 300 °C and 500 °C (REC-300 °C and REC-500 °C) were lower than REC. To investigate the mechanism, the materials before and after immobilization were fully analyzed by Fourier transform infrared spectroscopy (FT-IR), powdery X-ray diffraction analysis (XRD), and scanning electron microscopy (SEM). The results indicate that the structure of REC has been changed after calcination at different temperatures and Cd(II) was successfully immobilized on materials. Losing free water, structural water and OH groups respectively, the layer spacing of REC-300 °C and REC-500 °C was shrunk. However, the crystal structure of REC was destroyed after calcination at 700 °C, resulting in the generation of new phases. According to the XRD result, more cadmium hydroxide (Cd(OH)2) were produced on REC-700 °C, indicating that more OH groups were formed during immobilization. Furthermore, Tessier test demonstrates that Cd(II) in soil changed from exchangeable state and water soluble state to carbonate bound state and iron manganese oxide bound state during immobilization. The result of microbial community indicates that REC-700 °C can restore the microbial composition of Cd(II)-contaminated soil. The effects of pH, freeze-thaw, REC dosage, and initial heavy metal concentration were also evaluated to provide a theoretical basis for the subsequent application of the material in the remediation of contaminated soil.

Recent advances in Ti-based MOFs in biomedical applications.

Currently, metal-organic frameworks (MOFs), basically inorganic-organic hybrid materials, have gained tremendous attention due to their vast applications. MOFs have shown enormous applications in almost every research field. However, the area of designing MOF materials for their biological applications is still an emerging field that needs attention. Titanium-based metal-organic framework (Ti-MOF) materials are used in many research areas due to their structural advantages, such as small particle size and large effective surface area. On the other hand, they have also shown unique advantages such as good biocompatibility, excellent catalytic oxidation and photocatalytic properties and ease of functionalization. This study reviews the recent research progress on Ti-MOFs in therapeutic areas such as antibacterial, oncology, anti-inflammation, and bone injury, which will provide new directions for further research in this biomedical field. Therefore, this article will help scientists working in the particular field to enhance their understanding of Ti-based MOFs for functional biomedical applications.

Molecular profile reveals immune-associated markers of medulloblastoma for different subtypes.

Medulloblastoma, a common pediatric malignant tumor, has been recognized to have four molecular subgroups [wingless (WNT), sonic hedgehog (SHH), group 3, group 4], which are defined by the characteristic gene transcriptomic and DNA methylomic profiles, and has distinct clinical features within each subgroup. The tumor immune microenvironment is integral in tumor initiation and progression and might be associated with therapeutic responses. However, to date, the immune infiltrative landscape of medulloblastoma has not yet been elucidated. Thus, we proposed MethylCIBERSORT to estimate the degree of immune cell infiltration and weighted correlation network analysis (WGCNA) to find modules of highly correlated genes. Synthesizing the hub genes in the protein-protein interaction (PPI) network and modules of the co-expression network, we identify three candidate biomarkers [GRB2-associated-binding protein 1 (GAB1), Abelson 1 (ABL1), and CXC motif chemokine receptor type 4 (CXCR4)] via the molecular profiles of medulloblastoma. Given this, we investigated the correlation between these three immune hub genes and immune checkpoint blockade response and the potential of drug prediction further. In addition, this study demonstrated a higher presence of endothelial cells and infiltrating immune cells in Group 3 tumor bulk. The above results will be conducive to better comprehending the immune-related pathogenesis and treatment of medulloblastoma.

Liposomal honokiol promotes hair growth via activating Wnt3a/ß-catenin signaling pathway and down regulating TGF-ß1 in C57BL/6N mice.

Liposomal honokiol isolated from the genus Magnolia has been found to have antiangiogenic, anti-inflammatory and antitumor properties. However, there has no report on its role in hair growth. Hair follicles are life-long cycled organelles that go through from anagen, catagen and telogen stages and are regulated by diverse signaling pathways, including Wnt/ß-catenin, Notch, Epidermal growth factor (EGF) and Sonic hegehog (SHH). Wnt signals are essential for the initiation of hair follicle placode development and a new potential target of hair loss treatment. This study was designed to investigate the effect of liposomal honokiol (Lip-honokiol) on inducing hair anagen. We identified the hair grew out in advance in the shaving area of C57BL/6N mice after the treatment of liposomal honokiol (Lip-honokiol) by daily abdominal injection. We first demonstrated that Lip-Honokiol activated the Wnt3a/ß-catenin pathway and downregulated the transforming growth factor-ß1 (TGF-ß1) to promote hair growth in mice via immunohistochemistry and immunofluorescence staining. These findings suggest that Lip-honokiol activated the Wnt/ß-catenin pathway and accelerated the transfer from the telogen to anagen stage and finally promoted the hair growth.

Liposomal honokiol inhibits glioblastoma growth through regulating macrophage polarization.

BACKGROUND: Glioblastoma is a type of aggressive brain tumor-related to infiltrating microglia/macrophages. Various studies have identified antitumor properties of a bioactive plant compound named honokiol, originating from the Magnolia species. This beneficial characteristic of honokiol has been discovered in many malignant tumors. METHODS: We investigated the molecular mechanisms behind the anti-glioma effects of liposomal honokiol (Lip-HNK) using qRT-PCR, Western blot, co-culture, and in vivo animal experiments. RESULTS: It was discovered that the expression of M1 markers such as CD11c, inducible nitric oxide synthase (iNOS), and major histocompatibility complex (MHC) II (IA/IE subregions) induced by lipopolysaccharide (LPS)/IFN-γ was increased by Lip-HNK, and M2 markers Arg1 and CD206 induced by interleukin (IL)-4 had reduced expression, thus inhibiting tumor cell growth through co-culture experiments. After Lip-HNK treatment, a considerable increase in signal transducer and activator of transcription 1 (STAT1) activation was observed, and in contrast, STAT6 activation was suppressed. STAT1 and STAT6 are the key signaling molecules mediating M1 and M2 polarization, respectively. Furthermore, the percentage of CD11c-positive M1 macrophages was increased by Lip-HNK in G422 xenograft mice, while Lip-HNK treatment reduced the CD206-positive M2 macrophage distribution in tumor tissues. These findings are consistent with the decline in tumor volume seen in mice treated with Lip-HNK. CONCLUSIONS: Lip-HNK inhibits the growth of glioblastoma by upregulating M1 macrophages and limiting M2 phenotypic macrophages.

5-aminolevulinic acid-based photodynamic therapy associated with Itraconazole successfully treated a case of chromoblastomycosis.

Chromoblastomycosis (CBM) is a prevalent implantation fungal infection. Patients with CBM show chronic granulomatous hyperplasia with ulcers and exudation. It may cause incapacity for labor in some severe clinical forms and it is often refractory to antifungal therapies. There is no optimal treatment. Here we report a case of a 71-year-old male farmer with refractory CBM who was successfully treated with 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) and Itraconazole in 2 months. Clinical cure was achieved with no obvious side effects.

Low-level PDT treatment modulated photoaging mediated by UVA irradiation through regulating Bach2.

OBJECTIVE: To investigate low-level ALA-PDT (Aminolevulinic acid photodynamic therapy) effects on photorejuvenation in vitro and in vivo, exploring the basic mechanism of Bach2 involved in PDT treatment in photoaging. METHOD: Photoaging model was established by UVA chronic irradiation in human fibroblasts and mice skins. Cell viability was determined by MTS assay and cell senescence was detected by SA-ß-gal activity. PDT treatment and Bach2 knockdown with adenovirus in fibroblasts were confirmed by Western blot. RESULTS: UVA chronic irradiation induced photoaging in vitro and in vivo. Treatment of low-level PDT reduced photoaging by decreasing SA-ß-gal activity and cell senescence-related proteins levels of p16 and p21 in fibroblasts. Moreover, low-level PDT treatment accompany with Bach2 accumulation increased in fibroblasts and in mice skin tissues. Bach2 knockdown with adenovirus induced cell senescence and Bach2 depletion with PDT treatment some extent decreased SA-ß-gal activity, but was with no significant change of Bach2 itself and p16 protein levels in fibroblasts. CONCLUSION: Low-level PDT treatment decreased skin photoaging which might be through up-regulating Bach2.

Adsorption and reduction of chromium(VI) from aqueous solution using polypyrrole/calcium rectorite composite adsorbent.

Chromate is considered to be a toxic contaminant because of its potential to harm animal and human health. In this study, polypyrrole/calcium rectorite clay composites (PPy/Ca-REC composites) were prepared as a potential adsorbent, via in situ polymerization of pyrrole monomer for adsorption of Cr(VI) from aqueous solution. The XRD results indicated that the clay sheets were exfoliated in the prepared composites. SEM results showed good dispersion of the PPy on the clay sheets. The adsorption of Cr(VI) onto the PPy/Ca-REC adsorbent was highly pH-dependent, and the removal efficiency by PPy/Ca-REC composites was much higher than the PPy homopolymer. Adsorption kinetics followed a pseudo-second-order kinetic model with an equilibrium reached within 30-180 min. The adsorption isotherm data were fitted well by the Langmuir isotherm model with the maximum adsorption capacity of 714.29-833.33 mg/g at 25-45 °C. The PPy/Ca-REC composites could be regenerated and reused for three consecutive adsorption-desorption cycles without loss of the original removal efficiency for Cr(VI) removal. Furthermore, the selective adsorption of Cr(VI) was demonstrated in binary adsorption systems with coexisting ions. The mechanisms of Cr(VI) removal containing electrostatic interactions, ionic interaction as well as reduction of Cr(VI) to Cr(III), which could be observed by the XPS results.