Efficient Water Reforming of Biomass to H2 via Well-Organized Redox-Neutral Cleavage of C-C, O-H and C-H Bonds.

Hydrogen (H2) is a clean and environmentally friendly energy carrier. The depletion of fossil fuels makes renewable H2 production highly desirable. Water reforming of renewable biomass to hydrogen, with a relay of natural photosynthesis to biomass, would be an indirect pathway to realize the ideal but extremely challenging photocatalytic overall water splitting to hydrogen, with favorable thermodynamics. Since the seminal work of water reforming of biomass in 1980, great endeavors have been made. Nevertheless, hitherto, the entire kinetic pathway has been elusive, which seriously limits the reforming processes. Using a designed well-organized redox-neutral cleavage of C-C, O-H and C-H bonds enabled by photoelectrocatalysis, here, we show the efficient water reforming of biomass to hydrogen at room temperature, with a yield up to 93%. The clear insights into the kinetic pathway with oxidation of carbon radicals to carbon cations as the indicated rate-determining step, would cast brightness for efficient and sustainable hydrogen production to accelerate the hydrogen economy.

Encapsulation of astaxanthin in OSA-starch based amorphous solid dispersions with HPMCAS-HF/Soluplus® as effective recrystallization inhibitor.

In this study, the interaction among multifunctional excipients, including polysaccharides, cellulose derivatives, and surfactants, was particularly investigated, together with its impact on the physicochemical properties of astaxanthin amorphous solid dispersions (ASTX ASDs). It was indicated that Span 20 could rapidly form hemimicelles or aggregates in the presence of hypromellose acetate succinate HF (HPMCAS-HF, HF) or Soluplus®, while octenyl succinic anhydride modified starch (OSA-starch) efficiently assisted in the coalescence inhibition of drug-excipients aggregates, which was jointly beneficial to the recrystallization inhibition of amorphous ASTX. ASTX ASDs were further prepared with OSA-starch, HPMCAS-HF/Soluplus®, and Span 20 as the wall materials. DSC, SEM, and XRD confirmed that crystalline ASTX had transformed to amorphous state in the ASDs, while FT-IR spectra provided evidence suggesting the existence of hydrogen bonds and hydrophobic interaction between ASTX and the excipients. The dissolution of ASTX ASDs in different media revealed significant promotion, while the pharmacokinetic results further demonstrated the oral bioavailability of ASTX ASDs enhanced remarkably, exhibiting 2.75-fold (SD1) and 1.87-fold (SD2) increase, respectively, compared to ASTX bulk powder. In summary, the cellulose derivatives-surfactant interaction had great impact on the physicochemical properties of ASTX ASDs, and their combinations exhibited great potential for delivering the hydrophobic bioactive compounds efficiently.

MME and PTPRC: key renal biomarkers in lupus nephritis.

Background: Lupus nephritis (LN) is an autoimmune-related kidney disease with a poor prognosis, however the potential pathogenic mechanism remains unclear and there is a lack of precise biomarkers. Therefore, a thorough screening and identification of renal markers in LN are immensely beneficial to the research on its pathogenic mechanisms and treatment strategies. Methods: We utilized bioinformatics to analyze the differentially expressed genes (DEGs) at the transcriptome level of three clusters: total renal, glomeruli, and renal tubulointerstitium in the GEO database to discover potential renal biomarkers of LN. We utilized NephroSeq datasets and measured mRNA and protein levels in the kidneys of MRL/lpr mice to confirm the expression of key DEGs. Results: Seven significantly differential genes (EGR1, MME, PTPRC, RORC, MX1, ZBTB16, FKBP5) were revealed from the transcriptome database of GSE200306, which were mostly enriched in the pathway of the hematopoietic cell lineage and T cell differentiation respectively by KEGG and GO analysis. The seven hot differential genes were verified to have consistent change trends using three datasets from NephroSeq database. The receiver operating characteristic (ROC) curve indicated that five DEGs (PTPRC, MX1, EGR1, MME and RORC) exhibited a higher diagnostic ROC value in both the glomerulus and tubulointerstitium group. Validation of core genes using MRL/lpr mice showed that MME and PTPRC exhibit significantly differential mRNA and protein expression patterns in mouse kidneys like the datasets. Conclusions: This study identified seven key renal biomarkers through bioinformatics analysis using the GEO and NephroSeq databases. It was identified that MME and PTPRC may have a high predictive value as renal biomarkers in the pathogenesis of LN, as confirmed by animal validation.

Targeted metabolomics study of fatty-acid metabolism in lean metabolic-associated fatty liver disease patients.

BACKGROUND: The annual incidence of metabolic-associated fatty liver disease (MAFLD) in China has been increasing and is often overlooked owing to its insidious characteristics. Approximately 50% of the patients have a normal weight or are not obese. They are said to have lean-type MAFLD, and few studies of such patients are available. Because MAFLD is associated with abnormal lipid metabolism, lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis. AIM: To investigate the serum fatty-acid metabolic characteristics in lean-type MAFLD patients using targeted serum metabolomic technology. METHODS: Between January and June 2022, serum samples were collected from MAFLD patients and healthy individuals who were treated at Shanghai Putuo District Central Hospital for serum metabolomics analysis. Principal component analysis and orthogonal partial least squares-discriminant analysis models were developed, and univariate analysis was used to screen for biomarkers of lean-type MAFLD and analyze metabolic pathways. UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid (PA), oleic acid (OA), linoleic acid (LA), and arachidonic acid (AA) levels in lean-type MAFLD patients. RESULTS: Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.05). Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.01). The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals (P < 0.05) and the expression of triglycerides and fasting blood glucose were increased (P < 0.01). A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P < 0.05 and variable importance in projection > 1". The levels of PA, OA, LA, and AA were significantly increased compared with healthy individuals. CONCLUSION: The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly, yielding 65 identified biomarkers. PA, OA, LA, and AA exhibited the most significant changes, offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.

[Zirconium-based metal-organic framework composites for solid phase extraction of brevetoxin-A from seawater].

Red tides are a type of natural marine disaster caused by harmful algae characterized by a high toxicity, wide distribution, and long duration. Since the concentration of algal toxins in seawater increases with the occurrence of red tides, algal toxins detected in seawater could be used to predict the occurrence and evolution of red tides. Brevetoxin-A (BTX-A) is a secondary metabolite produced by the harmful algae Karenia brevis, whose detection in seawater could form the basis of an accurate warning system for incoming red tides. However, due to the inherent complexity of the seawater matrix and the extremely low levels of BTX-A in seawater, the use of instruments for its direct detection is difficult. Therefore, there is an urgent need to develop a sample pretreatment method for the efficient enrichment of BTX-A in seawater. In this study, a metal-organic backbone material (UiO-66) and its composite with silica microspheres (SiO2@UiO-66) were successfully synthesized using the solvothermal method. The prepared SiO2@UiO-66 exhibited good hydrophilicity, water stability, and large specific surface area. Furthermore, it also exhibited hydrogen bonding and electrostatic interactions with BTX-A, had a strong affinity for BTX-A, and was able to efficiently adsorb BTX-A in complex matrices. Therefore, SiO2@UiO-66 showed potential as a novel packing material for the extraction of BTX-A from solid phase extraction columns. Combined with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), a highly sensitive detection method for the determination of BTX-A in marine water was established. The established analytical method had a low detection limit (3.0 pg/mL), a wide linear range (10.0 -200.0 pg/mL), and a good linear relationship (R=0.9992). Combined with the Fujian Province Red Tide Monitoring and Early Warning Information 2021 issued by the Fujian Provincial Oceanic and Fisheries Bureau, the analytical method established herein was successfully applied to analyze and monitor the content of BTX-A in actual seawater samples. This highlights the proposed system's potential for use as an early warning factor in the monitoring of red tides, representing a simple and fast pretreatment methodology for the detection of BTX-A in seawater.

S100a8/a9 regulated by LPS/TLR4 axis plays an important role in Salmonella-based tumor therapy and host defense.

Bacteria are ideal anticancer agents and carriers due to their unique capabilities that are convenient in genetic manipulation, tumor-specific targeting, and deep-tissue penetration. However, the specific molecular mechanisms of bacteria-mediated cancer therapy (BMCT) have not been clarified. In this study, we found that TLR4 signaling pathway is critical for Salmonella-mediated tumor targeting, tumor suppression, and liver and spleen protection. TLR4 knockout in mice decreased the levels of cytokines and chemokines, such as S100a8, S100a9, TNF-α, and IL-1ß, in tumor microenvironments (TMEs) after Salmonella treatment, which inhibited tumor cell death and nutrient release, led to reduced bacterial contents in tumors and attenuated antitumor efficacy in a negative feedback manner. Importantly, we found that S100a8 and S100a9 played a leading role in Salmonella-mediated cancer therapy (SMCT). The antitumor efficacy was abrogated and liver damage was prominent when blocked with a specific inhibitor. These findings elucidated the mechanism of Salmonella-mediated tumor targeting, suppression, and host antibacterial defense, providing insights into clinical cancer therapeutics.

[Mechanism of HOXC6 promoting the progression of prostate cancer by activating the SFRP1/Wnt/ß-catenin signaling pathway].

OBJECTIVE: To study the expression of the Homeobox C6 (HOXC6) gene in the homeobox family in PCa, its effect on the biological behavior of PCa cells and its action mechanism. METHODS: Based on the studies of HOXC6 retrieved from the database of Gene Expression Profiling Interactive Analysis (GEPIA), we analyzed the expression of HOXC6 in PCa and the relationship of its expression level with the survival prognosis of the patients. We detected the expression of the HOXC6 protein in PCa tissues and cells by Western blot, stably interfered with the expression of the HOXC6 gene in human PCa DU145 and PC-3 cells and normal prostatic epithelial RWPE-1 cells using the siRNA plasmid, and determined the effects of HOXC6 on the proliferation, migration and invasiveness of PCa cells by CCK8, plate cloning and scratch healing and Transwell invasion assays. Using the GEPIA database, we analyzed the correlation of the Wnt tumor inhibitory factor-secreted frizzled-related protein 1 (SFRP1) gene with HOXC6, and detected the expressions of HOXC6, SFRP1, Wnt and ß-catenin in PC-3 cells after siRNA-HOXC6 transfection by Western blot. RESULTS: The expression of HOXC6 was dramatically higher in the PCa than in the normal prostate tissue (P< 0.01), and in the PCa cells than in the normal prostatic epithelial cells (P< 0.01). Bioinformatics analysis indicated a lower survival rate of the PCa patients with a high than those with a low HOXC6 expression (P = 0.011). The relative expression of the HOXC6 protein, absorbance value, number of clones formed and number of invaded cells were significantly lower in the siRNA group than in the negative controls (P< 0.05). According to the GEPIA database, highly expressed SFRP1 was associated with a good prognosis of PCa, and the protein expressions of Wnt and ß-catenin were markedly increased while that of SFRP1 decreased in the PCa PC-3 cell line (P< 0.05). The expressions of the Wnt and ß-catenin proteins were decreased and that of SFRP1 increased significantly in the siRNA-HOXC6 transfection group compared with those in the siRNA negative control and PCa PC-3 groups (P< 0.05). CONCLUSION: HOXC6 is highly expressed in PCa tissues and related to the proliferation, migration and invasiveness of PCa cells. HOXC6 promotes the growth of DU145 and PC-3 cells in PCa by inhibiting the SFRP1/Wnt/ß-catenin signaling pathway, and may be a potential target for clinical treatment of PCa.

ACSL4 upregulates IFI44 and IFI44L expression and promotes the proliferation and invasiveness of head and neck squamous cell carcinoma cells.

Reprogramming of cellular energy metabolism, including deregulated lipid metabolism, is a hallmark of head and neck squamous cell carcinoma (HNSCC). However, the underlying molecular mechanisms remain unclear. Long-chain acyl-CoA synthetase 4 (ACSL4), which catalyzes fatty acids to form fatty acyl-CoAs, is critical for synthesizing phospholipids or triglycerides. Despite the differing roles of ACSL4 in cancers, our data showed that ACSL4 was highly expressed in HNSCC tissues, positively correlating with poor survival rates in patients. Knockdown of ACSL4 in HNSCC cells led to reduced cell proliferation and invasiveness. RNA sequencing analyses identified interferon-induced protein 44 (IFI44) and interferon-induced protein 44-like (IFI44L), encoded by two interferon-stimulated genes, as potential effectors of ACSL4. Silencing IFI44 or IFI44L expression in HNSCC cells decreased cell proliferation and invasiveness. Manipulating ACSL4 expression or activity modulated the expression levels of JAK1, tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 1 (STAT1), interferon α (IFNα), IFNß, and interferon regulatory factor 1 (IRF1), which regulate IFI44 and IFI44L expression. Knockdown of IRF1 reduced the expression of JAK1, TYK2, IFNα, IFNß, IFI44, or IFI44L and diminished cell proliferation and invasiveness. Our results suggest that ACSL4 upregulates interferon signaling, enhancing IFI44 and IFI44L expression and promoting HNSCC cell proliferation and invasiveness. Thus, ACSL4 could serve as a novel therapeutic target for HNSCC.

Qualification rate and associated factors regarding COVID-19 clinical skills training based on scenario simulation teaching to medical staffs in China: a hospital-based cross-sectional study.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has accentuated the need for effective clinical skills training in infectious diseases. This study aimed to explore the influencing factors of infectious disease clinical skills training based on scenario simulation teaching for medical staff in China. METHODS: This hospital-based, cross-sectional study was conducted at the Third People's Hospital of Shenzhen between March and December 2022. Scenario simulation teaching was applied, and factors such as gender, educational level, professional background, and previous experience were examined to determine their impact on qualification outcomes. RESULTS: The study included participants primarily between the ages of 20-40 years, with a higher proportion of women holding university degrees. Nurses and physicians were more likely to qualify, indicating the significance of professional backgrounds. Women showed a higher likelihood of qualifying than men and higher educational attainment correlated with better qualification rates. Prior experience with protective clothing in isolation wards was a significant determinant of successful qualification. Multivariate analysis underscored the influence of sex, education, and previous experience on training effectiveness. CONCLUSION: Scenario simulation is an effective strategy for training clinical skills in treating infectious diseases. This study highlights the importance of considering sex, education, professional background, and prior experience when designing training programs to enhance the efficacy and relevance of infectious disease training.

Distinct roles and molecular mechanisms of nicotine and benzo(a)pyrene in ferroptosis of lung adenocarcinoma and lung squamous cell carcinoma.

INTRODUCTION: The essence of ferroptosis is the accumulation of membrane lipid peroxides caused by increased iron, which disrupts the redox balance within cells and triggers cell death. Abnormal metabolism of iron significantly increases the risk of lung cancer and induces treatment resistance. However, the roles and mechanisms of smocking in ferroptosis in patients with lung cancer are still unclear. METHODS: Our study was a secondary bioinformatics analysis followed by an experimental cell culture analysis. In this study, we identified the different ferroptosis-related genes and established the signature in lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) patients with different smocking status, based on The Cancer Genome Atlas (TCGA) database. Fanyl diphosphate fanyl transferase 1 (FDFT1) in LUSC patients and solute carrier one family member 5 (SLC1A5) in LUAD patients were confirmed to be related to ferroptosis. Next, we checked the roles of two main components of smoke, nicotine, and benzo(a)pyrene (BaP), in ferroptosis of non-small-cell lung cancer (NSCLC) cells. RESULTS: We confirmed that nicotine inhibited reactive oxygen species (ROS) levels and induced glutathione peroxidase (GPX4) expression, while the opposite roles of BaP were observed in NSCLC cells. Mechanically, nicotine protected NSCLC cells from ferroptosis through upregulation of epidermal growth factor receptor (EGFR) and SLC1A5 expression. BaP-induced ferroptosis in NSCLC cells depends on FDFT1 expression. CONCLUSIONS: In this study, the ferroptosis-associated gene signature was identified in LUAD and LUSC patients with different smoking status. We confirmed nicotine-protected LUAD and LUSC cells from ferroptosis by upregulating EGFR and SLC1A5 expression. BaP-induced ferroptosis in these cells depends on FDFT1 expression.