Lead ions (Pb2+), a highly hazardous and non-biodegradable heavy metal with severe biotoxic effects, pose significant risks to ecological systems and public health, necessitating the development of advanced monitoring strategies capable of specific and ultrasensitive recognition. Herein, a Z-scheme Bi2CrO6/In2S3 heterojunction was constructed as a photoelectrochemical (PEC) probe for the selective recognition and ultrasensitive quantification of trace Pb2+ in aquatic environments. Primarily, the Z-scheme Bi2CrO6/In2S3 heterojunction was fabricated through the in-situ growth of In2S3 onto hydrothermally synthesized Bi2CrO6, establishing an efficient charge-transfer bridge between the two semiconductors. This unique Z-scheme architecture between Bi2CrO6 and In2S3 significantly facilitates the separation and migration of photogenerated charge carriers, yielding an eruptible and stable photocurrent response. Leveraging this enhanced PEC behavior, the sensor enables ultrasensitive detection of Pb2+. By simply tuning the coating concentration, two distinct linear ranges are achieved: a low-concentration range (10 nM-10 mu M) complying with the World Health Organization guideline for drinking water with a detection limit of 6.12 nM (S/N = 3), and a broad range (500 nM-1000 mu M) for high-concentration scenarios. The sensor also exhibited excellent selectivity, reproducibility, and operational stability. Importantly, the practical applicability of the PEC sensor for Pb2+ assay was successfully validated in real water samples, achieving satisfactory recovery rates with high repeatability (RSD < 5%), which not only provides new insights into the interfacial charge-transfer dynamics involving hazardous metal ions but also establishes a reliable and sensitive paradigm for the on-site monitoring of heavy metal contaminants in environmental waters.
IntroductionAcinetobacter baumannii is a formidable pathogen renowned for its role in hospital-acquired infections. In recent years, largely due to antibiotic abuse and other reasons, bacteria are frequently exposed to sub-minimum inhibitory concentration (sub-MIC) levels of antibiotics. Accumulating evidence suggests that sub-MIC antibiotic pressure serves as a critical driver of bacterial resistance evolution and virulence adaptation. However, the regulatory mechanisms underlying antibiotic stress adaptation in A. baumannii remains poorly understood. The quorum sensing (QS) system is a key bacterial signaling network that senses population density and coordinates vital physiological functions and environmental adaptations. Targeting QS system to attenuate virulence and resistance represents a promising strategy for combating multi-drug-resistant infections. Nevertheless, the role of systems in regulating antibiotic stress response in A. baumannii has not been elucidated.MethodsIn this study, we used the wild-type (WT) strain of A. baumannii and an isogenic abaI deletion mutant strain (ΔabaI) to investigate the involvement of QS in adaptive responses under meropenem sub-MIC pressure. The analysis was performed by phenotypic experiments such as bacterial biofilm formation and motility detection, transcriptome sequencing (RNA-seq) and qRT-PCR verification.ResultsWe found that under antibiotic pressure, the WT strain developed significantly enhanced resistance, accompanied by increased biofilm formation, surface motility, adherence to and invasion of A549 cells, and pathogenicity in Galleria mellonella. In contrast, the ΔabaI strain showed no significant changes in resistance, motility, host cell adhesion and invasion, or virulence, with all these parameters remaining substantially lower than those of the antibiotic-treated WT. Interestingly, biofilm formation was still significantly enhanced in the ΔabaI strain, suggesting compensatory activation of alternative regulatory mechanisms. Transcriptomic analysis revealed that sub-MIC meropenem triggered extensive gene expression changes in both the WT and ΔabaI strains. In the WT, differentially expressed genes were enriched in pathways including quorum sensing, biofilm formation, ABC transporters, and two-component systems. In contrast, the ΔabaI mutant exhibited distinct transcriptional profiles, with enrichment in Δ-lactam resistance, aromatic amino acid biosynthesis, and metabolite transport. The expression trends of key virulence- and resistance-associated genes were further validated by qRT-PCR, confirming the reliability of the RNA-seq data.DiscussionOur study underscores the potential of targeting the QS system to mitigate antibiotic-driven adaptation and provides a strategic basis for controlling multidrug-resistant A. baumannii infections.
The interaction between B40M (M = K similar to Zn) nanocages and 5-fluorouracil (5-Fu) anticancer drug has been systematically investigated using density functional theory (DFT) in this study. The different doping modes and spin multiplicity have been explored to screen out the most stable B40M. Among these considered boron-based nanocages, B40M (M = K, Ti, V, and Fe) exhibit remarkable adsorption energies (E-ad = -18.91 similar to -20.41 kcal/mol) toward 5-Fu. It is found that the KO2 bond formed between B40K and 5-Fu shows typical ionic characteristics, while the M-O bonds between B40M (M = Ti, V, and Fe) and 5-Fu exhibit both of ionic and covalent bonding characteristics. Interestingly, the E-ad value of 5-Fu@B40V decreases from -20.34 to -9.61 kcal/mol in a weakly acidic environment. Based on these findings, the B40M (M = K, Ti, V, and Fe) nanocages are identified as promising drug carriers for 5-Fu and even other drugs.
Over the past few years, substantial progress with promising outcomes were achieved for the use of antibodies against programmed cell death protein 1 (PD-1) and its ligand (PD-L1) in immunotherapy. However, several issues still limit their effectiveness for anti-cancer therapy. Therefore, we designed a bispecific antibody (referred to as Ba-PL) against PD-L1 and T cell immune checkpoint lymphocyte activation gene-3 (LAG-3), in an attempt to block both targets to further improve immune efficacy against solid tumors. A bispecific T cell engager structure was used to connect the variable regions of the PD-L1 and LAG-3 antibodies in series. The antibody was prepared using a prokaryotic expression system, and its molecular and cellular-level affinity was assessed in vitro. Furthermore, we preliminarily evaluated its anti-tumor effects in mice. Collectively, the antibody prepared using the prokaryotic expression system had preferable tumor cell-targeting ability and blocked the interaction of PD-1 and LAG-3 with their ligands. Further, the results of the animal experiments demonstrated that the Ba-PL exerted a better anti-tumor effect in 4T1 and H22 tumor-bearing mice. Overall, our study suggests that this strategy has therapeutic potential for liver hepatocellular and breast invasive carcinoma.
Recently, the research on developing lead-free double-B-cation halide perovskites has attracted attention. However, Cs2InBiCl6, the most promising one, was shown to be thermodynamically unstable. To improve the stability, organic dication DiMA2+ (i. e., (CH2NH3)+(CH2)3(CH2NH3)+) is introduced to design the new double perovskite DiMAInBiX6 (X=Cl, Br, and I) based on Cs2InBiX6 by replacing two Cs+ with a DiMA2+. Density functional theory calculations were performed to study the geometric and photoelectric properties of the newly designed materials. Unlike Cs2InBiX6, both DiMAInBiCl6 and DiMAInBiBr6 can exist stably against decompositions, indicating that the replacement of Cs+ by DiMA2+ will improve stability of double perovskites due to the staple effect. In addition, the replacement causes an increase in the band gaps of DiMAInBiX6. Particularly, the calculated band gap of DiMAInBiBr6 (1.31 eV) is close to the optimal value of single junction perovskite solar cell (PSC). Under ideal conditions, the PSC model constructed with DiMAInBiBr6 performs the best in theoretical simulation. This work proposes DiMAInBiBr6 as a promising light absorber of PSC, which has high stability and photoelectric performance. It also suggests that the replacement of Cs+ by DiMA2+ may serve as a rational and practical way to design new organic-inorganic hybrid double perovskites.
PurposeThe purpose of our meta-analysis and systematic review was to evaluate and compare the diagnostic effectiveness of [18F]FET PET and [18F]FDOPA PET in detecting glioma recurrence.MethodsSensitivities and specificities were assessed using the DerSimonian and Laird methodology, and subsequently transformed using the Freeman-Tukey double inverse sine transformation. Confidence intervals were computed employing the Jackson method, while heterogeneity within and between groups was evaluated through the Cochrane Q and I² statistics. If substantial heterogeneity among the studies was observed (P < 0.10 or I² > 50%), we conducted meta-regression and sensitivity analyses. Publication bias was assessed through the test of a funnel plot and the application of Egger’s test. For all statistical tests, except for assessing heterogeneity (P < 0.10), statistical significance was determined when the two-tailed P value fell below 0.05.ResultsInitially, 579 publications were identified, and ultimately, 22 studies, involving 1514 patients(1226 patients for [18F]FET PET and 288 patients for [18F]FDOPA PET), were included in the analysis. The sensitivity and specificity of [18F]FET PET were 0.84 (95% CI, 0.75-0.90) and 0.86 (95% CI, 0.80-0.91), respectively, while for [18F]FDOPA PET, the values were 0.95 (95% CI, 0.86-1.00) for sensitivity and 0.90 (95% CI, 0.77-0.98) for specificity. A statistically significant difference in sensitivity existed between these two radiotracers (P=0.04), while no significant difference was observed in specificity (P=0.58).ConclusionIt seems that [18F]FDOPA PET demonstrates superior sensitivity and similar specificity to [18F] FET PET. Nevertheless, it’s crucial to emphasize that [18F]FDOPA PET results were obtained from studies with limited sample sizes. Further larger prospective studies, especially head-to-head comparisons, are needed in this issue.Systematic Review Registrationidentifier CRD42023463476
Acinetobacter baumannii is currently one of the most important opportunistic pathogens causing severe nosocomial infections worldwide. Quorum Sensing (QS) system is a widespread mechanism in bacteria to coordinate group behavior by sensing the density of bacterial populations and affect eukaryotic host cell. In Acinetobacter baumannii, AbaI protein is used as QS molecule synthetase to synthesize N- acyl homoserine lactones (AHLs). Currently, QS has made great progress in the study of drug resistance, but there is still a lack of complete understanding of its damage to host cells after adhesion and invasion. Thus, in this study, we examined the effects of abaI mutant (ΔabaI) on the functions of adhesion and invasion, cell viability, inflammation, apoptosis in A. baumannii infected A549 cells, to evaluate the effects of ΔabaI in a zebrafish model. We found the group infected with ΔabaI increased cell viability, reduced adhesion and invasion, cell injury, inflammatory cytokine production and apoptosis. By RNA-Seq, we explored the possibility that abaI stimulated A549 cells inflammation by A. baumannii infection via TLR4/MAPK signaling pathway. In addition, the ΔabaI significantly reduced pathogenicity and recruitment to neutrophils in zebrafish. These observations suggest that abaI plays a major role in A. baumannii infection.
Intermittent urethral catheter clamping is widely used to reduce secondary catheterization in patients after proctectomy; however, its effectiveness is unclear. This study investigated the effects of intermittent catheter clamping combined with active urination training (ICCAUT) on postoperative urinary dysfunction in patients after proctectomy. This retrospective cohort study analyzed data on patients who underwent laparoscopic/robotic-assisted proctectomy at a single medical center in China between July 2023 and January 2024. Patients received ICCAUT or free urinary drainage during the indwelling urethral catheter period after surgery. Data from the ICCAUT and free-drainage groups were compared. The primary outcome measure was urinary dysfunction. The secondary outcomes were urinary tract infections, time to first void after catheter removal, and urine volume during first voiding. Propensity-score matching (PSM), inverse probability-of-treatment weighting (IPTW), and multivariable logistic regression analyses were used to identify factors associated with urinary dysfunction. Among 360 eligible patients, 173 received a free-drainage strategy and 187 received ICCAUT. The incidence of urinary dysfunction was 52.5
Fly ash was used as raw material to prepare zeolites through silicate gels, assisted by the hydrothermal method. The silicate gels could be effectively formed in a few minutes in a molten alkali environment. The zeolites could be prepared by using these silicate gels through the hydrothermal method, which realizes the transformation from useless materials to highly valuable materials. The obtained zeolites were applied to the removal of ammonium in water, achieving the highvalue utilization of fly ash. The synthesized zeolites were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectrum (EDS), thermogravimetric (TG), and Fourier transform infrared (FTIR) spectroscopy. The study on the adsorption and removal of ammonium in water shows that the adsorption of ammonium is more in line with pseudo first-order kinetics, and the adsorption mainly occurs in the first 20 min. The adsorption can reach equilibrium in 30 min, and the maximum adsorption capacity can reach 49.1 mg/g. The adsorption capacity of ammonium has the best performance at pH = 5. Furthermore, within a certain range, an increase in temperature is beneficial for the removal of ammonium.
Bone defects and tumor cell residues after bone tumor resection have always been a challenge. We tried to investigate a kind of bioglass with both bone repair and tumor killing capability to achieve two birds with one stone. We used a Sol-Gel method to prepare the high porous magnetic bioglass (MBG) and then compounded the MBG with calcium sulfate (CS) bone cement to form the composite scaffold (CS-MBG). We found that the CS-MBG could reach about 43 °C under the condition of magnetic field in vitro. Under this condition, CS-MBG would release Ca2+ resulting in the cell death of calcium overload. Meanwhile, the suitable pH and osteogenic activity of CS-MBG can promote the postoperative bone repair and inhibit the growth of bone tumors. Our work has innovatively designed a magnetic bioglass and verified its mechanism of synergistic hyperthermia against tumor, providing a new idea for the treatment of tumor bone defects with magnetic bioglass.
Background:Gliomas are the most common primary tumors of the central nervous system and portend a poor prognosis. The efficacy of emerging and promising immunotherapies varies significantly among individuals. Distinction and transformation of cold and hot tumors may improve the antitumor efficacy of immunotherapy.Methods and Results:In this study, we constructed a necroptosis-related lncRNA module based on public databases. The association of this module with survival was assessed using the Cox regression, Kaplan-Meier survival analysis, and nomogram, external validation was also conducted in another public database. Furthermore, we performed gene set enrichment analysis (GSEA), immune checkpoint and tumor microenvironment analysis, and in vitro qRT-PCR validation. Finally, we clustered all samples into 2 clusters based on the expression of model lncRNAs and identified cluster 1 as cold tumors with fewer infiltrating T cells.Conclusions:Identifying cold and hot tumors by necroptosis-related lncRNAs can help available immunotherapeutic strategies to achieve efficacy in the precise treatment of individuals. Prior treatment failure can be overcome by targeting necroptosis-related lncRNAs.
The in situ anchoring of metal elements on the surface of nanomaterials is a state-of-the-art technology that can significantly enhance the performance of materials. We have successfully fabricated noble metal-ion modified rutile TiO2 nanobars, which exhibit exceptional catalytic activity in both H2 generation and CO oxidation. Firstly, we synthesized Ti3+ self-doped rutile TiO2-x nanobars by a simple solvothermal method using Zn as a reductant, resulting in highly crystalline structures with a significant proportion of (110) surfaces. The reduced nanobars chemically absorb the noble metal cations with the addition of a solution of a noble metal salt in the absence of light to form in situ noble metal-ion modified catalysts. TiO2 nanobars with 1 wt% Pt2+ and Pd2+ exhibited excellent performance in photocatalytic H2 generation from water and low temperature CO oxidation. Moreover, the samples modified with low noble metal ions (0.1 wt%) also show effective activity in H2 generation.
A new synthesis of propiolonitrile via Zn-participated electrophilic cyanation of alkynyl bromides with N-cyano-N-phenyl-p-methylbenzenesulfonamide (NCTS) has been developed here. The Zinc dust was used to activate the Csp-Br bond firstly by forming organozinc reagent that can react with electrophilic NCTS in the presence of tetrabutylammonium iodide (TBAI). Different phenylpropiolonitriles could be produced in moderate to excellent yields (51-95%) via this new simple protocol. The inactive alkynyl chlorides has also performed smoothly in this Zn-participated preparation of propiolonitrile as reactants cooperated with tetrabutylammonium bromide (TBAB) but desired products have been given in unsatisfactory yields (20-70%).
Background Glioblastoma (GBM) is the most common primary brain malignant tumor, and patients with GBM have a poor prognosis. The tumor microenvironment (TME) is connected to tumorigenesis and prognosis. However, the TME-related genes and therapeutic targets in GBM are yet to be identified. Thus, the presented study aimed to identify TME-related biomarkers in GBM and develop a novel target for the treatment of the disease. Methods ESTIMATE computational methods were utilized to estimate the amounts of stromal and immune components in 697 patients with glioma from the Cancer Genome Atlas database. Then, the protein–protein interaction network and univariate Cox regression analyzed the differentially expressed genes. Serum amyloid A1 (SAA1) was determined to be a predictive factor. SAA1 expression was statistically significant in GBM compared to the normal samples and other glioma subtypes and negatively associated with survival. Independent prognostic analysis identified SAA1 as a TME-related prognostic factor. Furthermore, Western blot analysis showed that SAA1 is upregulated in GBM, which was confirmed by the external validation in the Chinese Glioma Genome Atlas. The gene set enrichment analysis in GBM revealed enrichment of immune-related activities in the SAA1 high-expression group, while mitosis and cell cycle were enriched in the low-expression group. CIBERSORT analysis of the tumor-infiltrating immune cell proportion revealed that M2 macrophages, neutrophils, activated mast cells, resting mast cells, and regulatory T cells were correlated with SAA1 expression. Finally, immune checkpoint genes, tumor mutation burden, and drug sensitivity were also analyzed between the high- and low-expression groups. Conclusion SAA1 could be a distinctive gene between GBM and other subtype gliomas, and thus a novel biomarker for estimating the survival and TME status. The altered expression level shifts the primary function of SAA1 from cell cycle and mitosis to immune activity. High expression of SAA1 is associated with poor survival and upregulates the expression of LAIR1 and TNFSF14, thereby deeming it as the drug sensitivity indicator for XAV939, TGX-221, and lapatinib in GBM immune therapy.
C 11 H 11 NO 9 P 3 Zn, monoclinic, P 2 1 / n (no. 14), a = 12.619(2) Å, b = 8.4948(12) Å, c = 13.954(2) Å, β = 90.588(3)°, V = 1495.7(4) Å 3 , Z = 4, R gt ( F ) = 0.0413, wR ref ( F 2 ) = 0.0965, T = 120(2) K.
Arctigenin is the main active ingredient of the Chinese traditional medicine burdock, which can inhibit tumour growth and induce tumour cell apoptosis, but have almost no toxicity to normal cells. However, studies have shown that the bioavailability of arctigenin is low, which limits its medicinal efficacy and clinical application. Novel drug carriers have become a focus of anti-tumour research. Mesoporous silica has attracted widespread study as it has the advantages of good biocompatibility, large specific surface area, high drug loading capacity, adjustable pore size and easy surface modification. In this paper, mesoporous silica nanoparticles were used as a carrier and targeted with folic acid-ZnO to sustained-release and controlled-release dual modification, we constructed a novel self-responsive drug release system for the cell microenvironment. Drug loading and releasing ability were determined. The human ovarian cancer SK-OV-3 cell line was tested through cytotoxicity and cell uptake behaviour compared with the clinical anticancer drug paclitaxel. The double-modified arctigenin drug release system had similar killing effect on ovarian cancer cells as paclitaxel. The active ingredients of traditional Chinese medicine such as arctigenin can be easily adsorbed by mesoporous silica and become Nano-Chinese medicines, demonstrating potential applications in drug delivery systems.
C 42 H 52 N 18 O 10 Co, monoclinic, P 2 1 / c (no. 14), a = 11.3692(7) Å, b = 17.5938(10) Å, c = 12.1825(7) Å, β = 108.6360(10)°, V = 2309.1(2) Å 3 , Z = 2, R gt ( F ) = 0.0308, wR ref ( F 2 ) = 0.0765, T = 120(2) K.
C42H52N18O10Co, monoclinic, P21/c (no. 14), a = 11.3692(7) Å, b = 17.5938(10) Å, c = 12.1825(7) Å, β = 108.6360(10)°, V = 2309.1(2) Å3, Z = 2, Rgt(F) = 0.0308, wRref(F2) = 0.0765, T = 120(2) K.
C11H11NO9P3Zn, monoclinic, P21/n (no. 14), a = 12.619(2) Å, b = 8.4948(12) Å, c = 13.954(2) Å, β = 90.588(3)°, V = 1495.7(4) Å3, Z = 4, Rgt(F) = 0.0413, wRref(F2) = 0.0965, T = 120(2) K.
BACKGROUND:Acinetobacter baumannii (A. baumannii) is one of the most important pathogens that cause serious nosocomial infections worldwide. However, there are few reports on the virulence of A. baumannii clinical isolates, and little is known about the mechanism regulating virulence and drug resistance. The aim of this study was to determine the prevalence of drug resistance and virulence profiles and explore features related to quorum sensing (QS).METHODS:A total of 80 clinical A. baumannii isolates were collected from Jilin province of China from 2012 to 2017. We investigated these clinical isolates with respect to biofilm formation, surface motility, adherence, invasion into A549 human alveolar epithelial cells, and virulence to Galleria mellonella. We also explored the prevalence of the AbaI/AbaR QS system and its correlation with bacterial virulence and drug resistance.RESULTS:The resistance rates of the isolates to 17 commonly used antibiotics were higher than 50%, and 75% of the isolates were multi-drug resistant. Approximately 95% (76/80) of the isolates showed the ability to form biofilms, of which 38 showed strong biofilm formation ability (+++). Only 5 strains showed strong surface-related motility. A high level of variability was found in adherence and invasion into A549 epithelial cells, and 16 isolates showed strong virulence to Galleria mellonella (none survived after 6 days of infection). Of the 61 isolates carrying abaI and abaR genes, 24 were found to produce N-acyl homoserine lactones (AHLs) detectable by biosensor bacteria. Correlation analysis revealed that abaI and abaR genes positively correlated with bacterial resistance rates. All strains showing obvious surface-related motility carried abaI and abaR genes and produced AHLs. The isolates with detectable QS systems also showed stronger invasiveness into A549 cells and pathogenicity toward G. mellonella than the QS-deficient isolates.CONCLUSION:Our study demonstrates that the AbaI/AbaR QS system was widely distributed among the A. baumannii clinical isolates, was necessary for surface-related motility, and significantly correlated with drug resistance, invasion into epithelial cells, and virulence to G. mellonella.