Two Different Three-Dimensional Uranium-Containing Polymolybdates Based on Zn(II) for the Heterogeneous Catalytic Construction of C-N Bond.

The introduction of transition metal (TM) ions into polyoxometalates (POMs) cannot only bring about interesting structural diversities but also enable changes in properties. However, TM-containing Silverton-type polyoxomolybdates are still lacking in terms of structural diversity and application development. Herein, two Zn(II)-containing Silverton-type {UMo12O42}-based polyoxomolybdates, H1.89Na4.11(H2O)9Zn[UMo12O42]·4.5H2O (Zn-1) and H1.8Na4.2(H2O)12Zn[UMo12O42] (Zn-2) were hydrothermally synthesized, demonstrating a practical strategy to assembly of TM-containing Silverton-type POMs. Zn-1 is proven to be an excellent and recyclable heterogeneous catalyst in cross-dehydrogenation coupling of 1,4-naphthoquinones with amines reactions, and a series of 2-amino-1,4-naphthoquinones with potential medicinal value have been constructed.

Improving product quality and productivity of an antibody-based biotherapeutic using inverted frustoconical shaking bioreactors.

The Chinese hamster ovarian (CHO) cells serve as a common choice in biopharmaceutical production, traditionally cultivated in stirred tank bioreactors (STRs). Nevertheless, the pursuit of improved protein quality and production output for commercial purposes demand exploration into new bioreactor types. In this context, inverted frustoconical shaking bioreactors (IFSB) present unique physical properties distinct from STRs. This study aims to compare the production processes of an antibody-based biotherapeutic in both bioreactor types, to enhance production flexibility. The findings indicate that, when compared to STRs, IFSB demonstrates the capability to produce an antibody-based biotherapeutic with either comparable or enhanced bioprocess performance and product quality. IFSB reduces shear damage to cells, enhances viable cell density (VCD), and improves cell state at a 5-L scale. Consequently, this leads to increased protein expression (3.70 g/L vs 2.56 g/L) and improved protein quality, as evidenced by a reduction in acidic variants from 27.0% to 21.5%. Scaling up the culture utilizing the Froude constant and superficial gas velocity ensures stable operation, effective mixing, and gas transfer. The IFSB maintains a high VCD and cell viability at both 50-L and 500-L scales. Product expression levels range from 3.0 to 3.6 g/L, accompanied by an improved acidic variants attribute of 20.6%-22.7%. The IFSB exhibits superior productivity and product quality, underscoring its potential for incorporation into the manufacturing process for antibody-based biotherapeutics. These results establish the foundation for IFSB to become a viable option in producing antibody-based biotherapeutics for clinical and manufacturing applications.

KCTD5 regulates Ikaros degradation induced by chemotherapeutic drug etoposide in hematological cells.

Therapy-related leukemia carries a poor prognosis, and leukemia after chemotherapy is a growing risk in clinic, whose mechanism is still not well understood. Ikaros transcription factor is an important regulator in hematopoietic cells development and differentiation. In the absence of Ikaros, lymphoid cell differentiation is blocked at an extremely early stage, and myeloid cell differentiation is also significantly affected. In this work, we showed that chemotherapeutic drug etoposide reduced the protein levels of several isoforms of Ikaros including IK1, IK2 and IK4, but not IK6 or IK7, by accelerating protein degradation, in leukemic cells. To investigate the molecular mechanism of Ikaros degradation induced by etoposide, immunoprecipitation coupled with LC-MS/MS analysis was conducted to identify changes in protein interaction with Ikaros before and after etoposide treatment, which uncovered KCTD5 protein. Our further study demonstrates that KCTD5 is the key stabilizing factor of Ikaros and chemotherapeutic drug etoposide induces Ikaros protein degradation through decreasing the interaction of Ikaros with KCTD5. These results suggest that etoposide may induce leukemic transformation by downregulating Ikaros via KCTD5, and our work may provide insights to attenuate the negative impact of chemotherapy on hematopoiesis.

In situ self-referenced intracellular two-electrode system for enhanced accuracy in single-cell analysis.

Since the emergence of single-cell electroanalysis, the two-electrode system has become the predominant electrochemical system for real-time behavioral analysis of single-cell and multicellular populations. However, due to the transmembrane placement of the two electrodes, cellular activities can be interrupted by the transmembrane potentials, and the test results are susceptible to influences from factors such as intracellular solution, membrane, and bulk solution. These limitations impede the advancement of single-cell analysis. Here, we propose a highly miniaturized and integrated in situ self-referenced intracellular two-electrode system (IS-SRITES), wherein both the working and reference electrodes are positioned inside the cell. Additionally, we demonstrated the stability (0.28 mV/h) of the solid-contact in situ Ag/AgCl reference electrode and the ability of the system to conduct standard electrochemical testing in a wide pH range (pH 6.0-8.0). Cell experiments confirmed the non-destructive performance of the electrode system towards cells and its capacity for real-time monitoring of intra- and extracellular pH values. Moreover, through equivalent circuits, finite element simulations, and drug delivery experiments, we illustrated that the IS-SRITES can yield more accurate test results and exhibit enhanced resistance to interference from the extracellular environment. Our proposed system holds the potential to enable the precise detection of intracellular substances and optimize the existing model of the electrode system for intracellular signal detection, thereby spearheading advancements in single-cell analysis.

Do People Prefer Home Palliative Care? A Survey Study and Assessment of Associated Factors in China.

Objectives: This study examined people's preference for the location to receive palliative care services and determined the associated factors. Methods: A questionnaire with reference to the Chinese version of the Hospice Attitude Scale and the Death Correspondence Scale was designed, piloted, revised, and distributed online and in person to collect data (N = 762). Binary logistic regression was used to analyze the effects of relevant factors. Results: The average age of the participants was 38.1, with a relatively even gender distribution. Over 90% of the participants were either single/never married (44.9%) or married with children (46.0%). 58.1% of the respondents (N = 428) indicated that they would like to receive palliative care at home, compared to 41.9% who preferred receiving such care in institutions or other places (N = 309). Each time people's attitudes toward death became one point more positive, they were 10.2% more likely to choose to receive palliative care services at home. People with a neutral attitude toward palliative care, single/never married or divorced with children, and having/had an occupation in health and social work had higher odds of preferring receiving palliative care at home. Those who had poor self-rated health or with an educational background of primary school or lower or some college had lower odds of preferring receiving palliative care at home. Conclusions: The research showed that attitudes toward death and other factors were associated with people's preferences for palliative care locations. More accessible and affordable community-based and home-based palliative care services should be further explored and provided.

A novel IQ mismatch compensation method in wideband direct-conversion receivers.

Direct-conversion receivers (DCRs) have been widely used in recent years due to their small size and low power consumption. However, the mismatch between the in-phase (I) and the quadrature (Q) branches will seriously affect the performance of the DCRs. This paper proposes a novel blind compensation method to suppress the interference introduced by IQ mismatch. Based on the Hilbert transform, our proposed method can obtain the orthogonal signal of the I-channel signal by utilizing the Weaver architecture. Compared with traditional compensation methods, the main difference of the proposed method is that it ignores prior information, training sequences, and additional hardware circuits. Furthermore, the complexity of the proposed blind compensation method is low because no iterative operations are involved in the compensation process. The simulation results show that the proposed method has an excellent compensation performance, especially in wideband applications.

PRRG4 regulates mitochondrial function and promotes migratory behaviors of breast cancer cells through the Src-STAT3-POLG axis.

BACKGROUND: Breast cancer is the leading cause of cancer death for women worldwide. Most of the breast cancer death are due to disease recurrence and metastasis. Increasingly accumulating evidence indicates that mitochondria play key roles in cancer progression and metastasis. Our recent study revealed that transmembrane protein PRRG4 promotes the metastasis of breast cancer. However, it is not clear whether PRRG4 can affect the migration and invasion of breast cancer cells through regulating mitochondria function. METHODS: RNA-seq analyses were performed on breast cancer cells expressing control and PRRG4 shRNAs. Quantitative PCR analysis and measurements of mitochondrial ATP content and oxygen consumption were carried out to explore the roles of PRRG4 in regulating mitochondrial function. Luciferase reporter plasmids containing different lengths of promoter fragments were constructed. Luciferase activities in breast cancer cells transiently transfected with these reporter plasmids were analyzed to examine the effects of PRRG4 overexpression on promoter activity. Transwell assays were performed to determine the effects of PRRG4-regulated pathway on migratory behaviors of breast cancer cells. RESULTS: Analysis of the RNA-seq data revealed that PRRG4 knockdown decreased the transcript levels of all the mitochondrial protein-encoding genes. Subsequently, studies with PRRG4 knockdown and overexpression showed that PRRG4 expression increased mitochondrial DNA (mtDNA) content. Mechanistically, PRRG4 via Src activated STAT3 in breast cancer cells. Activated STAT3 in turn promoted the transcription of mtDNA polymerase POLG through a STAT3 DNA binding site present in the POLG promoter region, and increased mtDNA content as well as mitochondrial ATP production and oxygen consumption. In addition, PRRG4-mediated activation of STAT3 also enhanced filopodia formation, migration, and invasion of breast cancer cells. Moreover, PRRG4 elevated migratory behaviors and mitochondrial function of breast cancer cells through POLG. CONCLUSION: Our results indicate that PRRG4 via the Src-STAT3-POLG axis enhances mitochondrial function and promotes migratory behaviors of breast cancer cells.

Dissecting climate change risk and financial market instability: Implications for ecological risk management.

This research investigates the impact of climate challenges on financial markets by introducing an innovative approach to measure climate risk, specifically the aggregate climate change concern (ACCC) index. The study aims to assess and quantify the potential influence of climate change and risk-related factors on the performance and dynamics of financial markets. In this paper, concern is defined as the attention paid to the risk of climate change and the associated negative consequences. The findings demonstrate that the aggregate index exhibits robust predictability of market risk premiums, both within the sample and out-of-sample. By comparison, the index contains additional information beyond 14 economic predictors and 12 risk/uncertainty indexes in forecasting stock market return. In addition, the index proves valuable for mean-variance investors in asset allocation, leading to significant economic gains. The study identifies the index's ability to capture the reversal of temporary price crashes caused by overreactions to climate change risk. Furthermore, it exhibits stronger return forecasting capability for green stocks, non-state-owned enterprise (non-SOE) stocks, and stocks in regions with low air pollution. Particularly during periods of low air pollution and relaxed regulation, the index displays an enhanced ability to forecast returns. The study's findings provide valuable insights for policymakers and financial institutions as they address 21st-century environmental challenges. Moreover, these findings can inform the design of adaptive measures and interventions aimed at mitigating ecological risks and promoting sustainable economic growth.

Multifunctional IrOx Neural Probe for In Situ Dynamic Brain Hypoxia Evaluation.

Perioperative cerebral hypoxia and neonatal hypoxia-ischemic encephalopathy are the main triggers that lead to temporary or permanent brain dysfunction. The pathogenesis is intimately correlated to neural activities and the pH of the microenvironment, which calls for a high demand for in situ multitype physiological signal acquisition in the brain. However, conventional pH sensing neural interfaces cannot obtain the characteristics of multimodes, multichannels, and high spatial resolution of physiological signals simultaneously. Here, we report a multifunctional implantable iridium oxide (IrOx) neural probe (MIIONP) combined with electrophysiology recording, in situ pH sensing, and neural stimulation for real-time dynamic brain hypoxia evaluation. The neural probe modified with IrOx films exhibits outstanding electrophysiology recording and neural stimulation performance and long-term stable high spatial pH sensing resolution of about 100 µm, and the cytotoxicity of IrOx microelectrodes was investigated as well. In addition, 4 weeks' tracking of the same neuron firing and instantaneous population spike captured during electrical stimulation was achieved by MIIONP. Finally, in a mouse brain hypoxia model, the MIIONP has demonstrated the capability of synchronous in situ recording of the pH and neural firing changes in the brain, which has a valuable application in dynamic brain disease evaluation through real-time acquisition of multiple physiological signals.

Lithium Iron Phosphate and Layered Transition Metal Oxide Cathode for Power Batteries: Attenuation Mechanisms and Modification Strategies.

In the past decade, in the context of the carbon peaking and carbon neutrality era, the rapid development of new energy vehicles has led to higher requirements for the performance of strike forces such as battery cycle life, energy density, and cost. Lithium-ion batteries have gradually become mainstream in electric vehicle power batteries due to their excellent energy density, rate performance, and cycle life. At present, the most widely used cathode materials for power batteries are lithium iron phosphate (LFP) and LixNiyMnzCo1-y-zO2 cathodes (NCM). However, these materials exhibit bottlenecks that limit the improvement and promotion of power battery performance. In this review, the performance characteristics, cycle life attenuation mechanism (including structural damage, gas generation, and active lithium loss, etc.), and improvement methods (including surface coating and element-doping modification) of LFP and NCM batteries are reviewed. Finally, the development prospects of this field are proposed.

Oil palm kernel globulin antihypertensive peptides: isolation and characterization, ACE inhibition mechanisms, zinc-chelating activity, security and stability.

Introduction: The oil palm kernel (OPK) expeller is the main byproduct of palm oil, but its utilization is limited. Methods: To obtain angiotensin-I-converting enzyme (ACE) inhibition peptides with Zn-chelating capacity, defatted oil palm kernel globulin hydrolysates (DOPKGH) were subjected to Sephadex G-15 gel electrophoresis, reverse-phase high liquid performance chromatography, and UPLC-ESI-MS/MS analysis. Results and discussion: Five representative oligopeptides, including Gln-Arg-Leu-Asp-Arg-Cys-Lys (QRLERCK), Leu-Leu-Leu-Gly-Val-Ala-Asn-Tyr-Arg (LLLGVANYR), Arg-Ala-Asp-Val-Phe-Asn-Pro-Arg (RADVFNPR), Arg-Val-Ile-Lys-Tyr-Asn-Gly-Gly-Gly-Ser-Gly (RVIKYNGGGSG), and Glu-Val-Pro-Gln-Ala-Tyr-Ile-Pro (EVPQAYIP), without potential toxicity and allergenicity, were identified in DOPKGH. Of these, only EVPQAYIP showed both ACE-inhibitory activity (IC50: 102.75 µmol/L) and Zn-chelating capacity (11.69 mg/g). Molecular docking and inhibition kinetics showed that EVPQAYIP was a competitive inhibitor of ACE because it could bind to Glu384, Lys511, and Gln281 (belonging to the central S1 and S2 pockets, respectively) of ACE. Moreover, EVPQAYIP affects zinc tetrahedral coordination in ACE by binding to Glu411; the amino and carboxyl groups of EVPQAYIP chelate with zinc ions. During gastrointestinal digestion, the ACE inhibitory activity of EVPQAYIP was relatively stable. Additionally, EVPQAYIP enhanced zinc stability in the intestine and exerted antihypertensive effects in spontaneous hypertensive rats. These results suggest the potential application of OPK peptides as ingredients in antihypertensive agents or zinc fortification.

Mechanism of IRF5-regulated CXCL13/CXCR5 Signaling Axis in CCI-induced Neuropathic Pain in Rats.

BACKGROUND: Neuropathic pain is chronic and affects the patient's life. Studies have shown that IRF5 and CXCL13/CXCR5 are involved in neuropathic pain; however, their interactions are unknown. OBJECTIVE: In this study, a rat neuropathic pain model was constructed by inducing chronic compression injury (CCI). IRF5 recombinant lentiviral vector and CXCL13 neutralizing antibody were administered to investigate their action mechanisms in neuropathic pain. Consequently, the new strategies for disease treatment could be evolved. METHODS: The CCI rats were intrathecally injected with recombinant lentivirus plasmid LV-IRF5 (overexpression), LV-SH-IRF5 (silencing), and CXCL13 neutralizing antibody. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured. The tumor necrosis factor (TNF)-alpha, interleukin (IL)-1ß, and IL-6 levels were recorded via the enzyme-linked immunosorbent assay (ELISA). The spinal cord was stained using hematoxylin-eosin (HE). The binding of IRF5 to CXCL13 was analyzed by chromatin immunoprecipitation (ChIP) and dual luciferase reporter assay. The IRF5, neuronal nuclei (NeuN), CXCL13, and CXCR5 expressions were detected through quantitative real-time polymerase chain reaction and Western blot. RESULTS: The MWT and TWL values in the CCI group were lower than in the Sham group. The expressions of CXCL13, CXCR5, and IRF5 in CCI rats were gradually increased with the modeling time. IRF5 silencing suppressed the expression of NeuN and lumbar enlargement in CCI rats and promoted MWT and TWL. Moreover, IRF5 silencing inhibited the expressions of CXCR5 and CXCL13 genes and down-regulated the expression levels of inflammatory factors. IRF5 was directly and specifically bound with the endogenous CXCL13 promoter and thus regulated it. IRF5 overexpression exacerbated the disease phenotype of CCI-induced neuropathic pain in rats. Administration of CXCL13 neutralizing antibodies reversed the IRF5 overexpression effects. CONCLUSION: The IRF5 silencing alleviated neuropathic pain in CCI rats by downregulating the pain threshold, inflammatory cytokine levels, and CXCL13/CXCR5 signaling. IRF5 overexpression exacerbated the disease parameters of CCI-induced neuropathic pain in rats; however, they were reversed by neutralizing antibodies against CXCL13.

Celastrol attenuates diabetic nephropathy by upregulating SIRT1-mediated inhibition of EZH2related wnt/ß-catenin signaling.

Proteinuria is an independent risk factor for the progression of diabetic nephropathy (DN) and an imbalance in podocyte function aggravates proteinuria. Celastrol is the primary active ingredient of T. wilfordii, effective in treating DN renal injury; however, the mechanisms underlying its effect are unclear. We explored how celastrol prevents DN podocyte damage using in vivo and in vitro experiments. We randomly divided 24 male C57BLKS/J mice into three groups: db/m (n = 8), db/db (n = 8), and celastrol groups (db/db + celastrol, 1 mg/kg/d, gavage administration, n = 8). In vivo experiments lasted 12 weeks and intervention lasted ten weeks. Serum samples and kidney tissues were collected for biochemical tests, pathological staining, transmission electron microscopy, fluorescencequantitation polymerase chain reaction, and western blotting analysis. In vitro experiments to elaborate the mechanism of celastrol protection were performed on high glucose (HG)-induced podocyte injury. Celastrol reduced blood glucose levels and renal function index in db/db mice, attenuated renal histomorphological injury and glomerular podocyte foot injuries, and induced significant anti-inflammatory effects. Celastrol upregulated silent information regulator 2 related enzyme 1(SIRT1) expression and downregulated enhancer of zeste homolog (EZH2), inhibiting the wnt/ß-catenin pathway-related molecules, such as wnt1, wnt7a, and ß-catenin. SIRT1 repressed the promoter activity of EZH2, and was co-immunoprecipitated with EZH2 in mouse podocyte cells (MPC5). SIRT1 knockdown aggravated the protective effects of celastrol on MPC5 cells. Celastrol protected podocyte injury via SIRT1/EZH2, which participates in the wnt/ß-catenin pathway. Overall, celastrol-mediated SIRT1 upregulation inhibited the EZH2-related wnt/ß-catenin signaling pathway to attenuate DN and podocyte injury, providing a theoretical basis for celastrol clinical application.

UV-Activated Au Modified TiO2/In2O3 Hollow Nanospheres for Formaldehyde Detection at Room Temperature.

Au modified TiO2/In2O3 hollow nanospheres were synthesized by the hydrolysis method using the carbon nanospheres as a sacrificial template. Compared to pure In2O3, pure TiO2, and TiO2/In2O3 based sensors, the Au/TiO2/In2O3 nanosphere-based chemiresistive-type sensor exhibited excellent sensing performances to formaldehyde at room temperature under ultraviolet light (UV-LED) activation. The response of the Au/TiO2/In2O3 nanocomposite-based sensor to 1 ppm formaldehyde was about 5.6, which is higher than that of In2O3 (1.6), TiO2 (2.1), and TiO2/In2O3 (3.8). The response time and recovery time of the Au/TiO2/In2O3 nanocomposite sensor were 18 s and 42 s, respectively. The detectable formaldehyde concentration could go down as low as 60 ppb. In situ diffuse reflectance Fourier transform infrared spectroscopy (DRIFTS) was used to analyze the chemical reactions on the surface of the sensor activated by UV light. The improvement in the sensing properties of the Au/TiO2/In2O3 nanocomposites could be attributed to the nanoheterojunctions and electronic/chemical sensitization of the Au nanoparticles.

Combining phthalimide innate of a positive-charge nanofiltration membrane for high selectivity and rejection for bivalent cations.

A positively charged nanofiltration (NF) membrane is known to have exceptional separation performance for bivalent cations in aqueous solutions. In this study, a new NF activity layer was created using interfacial polymerization (IP) on a polysulfone (PSF) ultrafiltration substrate membrane. The aqueous phase combines the two monomers of polyethyleneimine (PEI) and phthalimide, while successfully producing a highly efficient and accurate NF membrane. The conditions of the NF membrane were studied and further optimized. The aqueous phase crosslinking process enhances the polymer interaction, resulting in an excellent pure water flux of 7.09 L·m-2·h-1·bar-1 under a pressure of 0.4 MPa. Additionally, the NF membrane shows excellent selectivity toward inorganic salts, with a rejection order of MgCl2 > CaCl2 > MgSO4 > Na2SO4 > NaCl. Under optimal conditions, the membrane was able to reject up to 94.33% of 1,000 mg/L of MgCl2 solution at an ambient temperature. Further to assess the antifouling properties of the membrane with bovine serum albumin (BSA), the flux recovery ratio (FRR) was calculated to be 81.64% after 6 h of filtration. This paper presents an efficient and straightforward approach to customize a positively charged NF membrane. We achieve this by introducing phthalimide, which enhances the membrane's stability and rejection performance.

Cathepsin B S-nitrosylation promotes ADAR1-mediated editing of its own mRNA transcript via an ADD1/MATR3 regulatory axis.

Genetic information is generally transferred from RNA to protein according to the classic "Central Dogma". Here, we made a striking discovery that post-translational modification of a protein specifically regulates the editing of its own mRNA. We show that S-nitrosylation of cathepsin B (CTSB) exclusively alters the adenosine-to-inosine (A-to-I) editing of its own mRNA. Mechanistically, CTSB S-nitrosylation promotes the dephosphorylation and nuclear translocation of ADD1, leading to the recruitment of MATR3 and ADAR1 to CTSB mRNA. ADAR1-mediated A-to-I RNA editing enables the binding of HuR to CTSB mRNA, resulting in increased CTSB mRNA stability and subsequently higher steady-state levels of CTSB protein. Together, we uncovered a unique feedforward mechanism of protein expression regulation mediated by the ADD1/MATR3/ADAR1 regulatory axis. Our study demonstrates a novel reverse flow of information from the post-translational modification of a protein back to the post-transcriptional regulation of its own mRNA precursor. We coined this process as "Protein-directed EDiting of its Own mRNA by ADAR1 (PEDORA)" and suggest that this constitutes an additional layer of protein expression control. "PEDORA" could represent a currently hidden mechanism in eukaryotic gene expression regulation.

Antitumor effect of a novel humanized MUC1 antibody-drug conjugate on triple-negative breast cancer.

Breast cancer is the most common malignant cancer in women. Triple-negative breast cancer (TNBC) has a poorer prognosis than other subtypes and is challenging to treat. MUC1 is a therapeutic target in breast and pancreatic cancer. We developed a novel humanized antibody that specifically binds MUC1 expressed in breast cancer cells and conjugated a humanized MUC1 (HzMUC1) antibody to monomethyl auristatin (MMAE). HzMUC1-MMAE showed an anti-proliferative effect on HER2 positive trastuzumab-resistant breast cancer. Immunoprecipitation indicated that HzMUC1 recognized native MUC1 in TNBC cells. Confocal microscopy showed that HzMUC1 bound MUC1 on the surface of TNBC cells, and the conjugates exhibited the same binding ability to HCC70 as unconjugated HzMUC1 by cell-based ELISA. Treatment of TNBC cells with HzMUC1-MMAE reduced growth of MUC1-positive cells and induced G2/M cell cycle arrest and apoptosis. In a mouse model of breast cancer, HzMUC1-MMAE significantly reduced the growth of tumors established by subcutaneous injection of HCC70 TNBC cells. Therefore, HzMUC1-ADC has therapeutic potential for TNBC.

Effect of B-Site Element on the Structure and Catalytic Performance for Toluene of the 3DOM CeBO3 Catalyst.

A series of 3DOM cerium-based perovskite catalysts with different B-site elements were prepared by the colloidal crystal template method and excess impregnation method with Cr, Ni, and Mn as the B-site elements. The physical and chemical properties of the catalysts were investigated by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), hydrogen temperature-programmed reduction (H2-TPR), and oxygen temperature-programmed desorption (O2-TPD) characterization techniques. The results showed that the catalyst with Mn as the B-site element had a high-quality macropore structure (pore size 200-250 nm), large specific surface area (45.26 m2/g), and abundant surface adsorbed oxygen content (Oads/Olatt = 0.46). The addition of manganese enhanced the low-temperature reducibility, and the main reduction peak was below 400 °C. The O2-TPD results showed that 3DOM CeMnO3 expressed the highest adsorption oxygen content. The 3DOM CeMnO3 possessed the best catalytic performance with T50% = 102 °C and T90% = 203 °C during the catalytic oxidation of toluene. Intermediate product study hinted that toluene was first converted into benzoic acid and benzaldehyde and then further degraded into small molecules. The catalyst with the best activity also exhibited good stability, and toluene degradation rate remained above 85% at 200°C for more than 20 h of continuous experiments.

Vesicle-mediated transport-related genes are prognostic predictors and are associated with tumor immunity in lung adenocarcinoma.

Background: Globally, lung adenocarcinoma (LUAD) is the leading cause of cancer-related deaths. It is a progressive disorder that arises from multiple genetic and environmental factors. Dysregulated expression of vesicle-mediated transport-related genes (VMTRGs) have been reported in several cancers. However, the prognostic significance of VMTRGs in LUAD has yet to be established. Methods: The VMTRG profiling data for 482 LUAD patients and 59 normal controls were downloaded from The Cancer Genome Altas (TCGA). Univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were performed to construct and optimize the risk model. Several GEO datasets were used to validate the risk model. The roles of these genes were investigated via the Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analyses. Differences in immune cell infiltrations between risk groups were evaluated using five algorithms. "pRRophetic" was used to investigate anti-cancer drug sensitivities in two groups. Expression of these five genes in LUAD samples and adjacent normal tissues were evaluated by qRT-PCR. Colony formation and wound healing assays were performed to assess the significance of CNIH1 and AP3S1 in LUAD cells. Results: We identified 85 prognosis-associated VMTRGs that could be constructed a risk model for LUAD patients, indicating their potential importance in LUAD development. The risk model including the five VMTRGs (CNIH1, KIF20A, GALNT2, GRIA1, and AP3S1) was associated with clinical outcomes. Tumor stage and risk score were found to be independent prognostic factors for LUAD patients. The five VMTRGs were also correlated with activation of the Notch and p53 signaling pathways. The risk model was significantly associated with immune responses and with high-level expression of immune checkpoints. High-risk group patients were more sensitive to several chemotherapeutic drugs and Lapatinib. Furthermore, CNIH1 and AP3S1 promoted LUAD cell growth and migration in vitro. Conclusion: We constructed a VMTRG-based risk model for effective prediction of prognostic outcomes for LUAD patients. The risk model was associated with immune infiltration levels. These five hub genes are potential targets for immune therapy combined with chemotherapy in LUAD.

Therapeutic effect of a MUC1-specific monoclonal antibody-drug conjugates against pancreatic cancer model.

BACKGROUND: Pancreatic cancer is one of the most aggressive malignancies without effective targeted therapies. MUC1 has emerged as a potential common target for cancer therapy because it is overexpressed in a variety of different cancers including the majority of pancreatic cancer. However, there are still no approved monoclonal antibody drugs targeting MUC1 have been reported. Recently, we generated a humanized MUC1 antibody (HzMUC1) specific to the interaction region between MUC1-N and MUC1-C. In this study, we generated the antibody drug conjugate (ADC) by conjugating HzMUC1 with monomethyl auristatin (MMAE), and examined the efficacy of HzMUC1-MMAE against the MUC1-positive pancreatic cancer in vitro and in vivo. METHODS: Western blot and immunoprecipitation were used to detect MUC1 in pancreatic cancer cells. MUC1 localization in pancreatic cancer cells was determined by confocal microscopy. HzMUC1 was conjugated with the monomethyl auristatin (MMAE), generating the HzMUC1-MMAE ADC. Colony formation assay and flow cytometry were used to assess the effects of the HzMUC1-MMAE cell viability, cell cycle progression and apoptosis. Capan-2 and CFPAC-1 xenograft model were used to test the efficacy of HzMUC1-MMAE against pancreatic cancer. RESULTS: HzMUC1 antibody binds to MUC1 on the cell surface of pancreatic cancer cells. HzMUC1-MMAE significantly inhibited cell growth by inducing G2/M cell cycle arrest and apoptosis in pancreatic cancer cells. Importantly, HzMUC1-MMAE significantly reduced the growth of pancreatic xenograft tumors by inhibiting cell proliferation and enhancing cell death. CONCLUSION: Our results indicate that HzMUC1-ADC is a promising novel targeted therapy for pancreatic cancer. HzMUC1-ADC should also be an effective drug for the treatment of different MUC1-positive cancers.