Synergetic-effect-enhanced electrochemiluminescence of zein-protected Au-Ag bimetallic nanoclusters for CA15-3 detection.

In this work, a sandwich-type electrochemiluminescence (ECL) system was constructed for the detection of CA15-3. Gold-silver bimetallic nanoclusters (Au-Ag BNCs) with zein as a protective ligand were synthesized, and the excellent ECL performance of this material was demonstrated for the first time. Zein carrying a variety of groups that ligated with Au-Ag BNCs, forming a protective shell of zein, effectively prevented clusters from aggregating or growing into larger nanoparticles. The synergistic effect of the bimetal promotes the ECL emission, making this nanoscale material an ideal ECL probe. GO-PANI, which effectively promoting the production of sulfate radicals of the co-reactant and significantly increasing the ECL strength, was a good sensing platform for antibody immobilization. Consequently, we constructed an ECL sensor with GO-PANI as the sensing platform and Au-Ag BNCs@zein as the ECL probe, with a detection range of 0.001-100 U mL-1 and a detection limit of 0.0003 U mL-1, provided a strong support for the sensor for future CA15-3 detection applications.

Pharmacological effect and mechanism of orlistat in anti-tumor therapy: A review.

Research has demonstrated that obesity is an important risk factor for cancer progression. Orlistat is a lipase inhibitor with promising therapeutic effects on obesity. In addition to being regarded as a slimming drug, a growing number of studies in recent years have suggested that orlistat has anti-tumor activities, while the underlying mechanism is still not well elucidated. This paper reviewed recent pharmacological effects and mechanisms of orlistat against tumors and found that orlistat can target cancer cells through activation or suppression of multiple signaling pathways. It can induce tumor cells apoptosis or death, interfere with tumor cells' cycles controlling, suppress fatty acid synthase activity, increase ferroptosis, inhibit tumor angiogenesis, and improve tumor cells glycolytic. Thus, this review may shed new light on anti-tumor mechanism and drug repurposing of orlistat, and anti-tumor drug development.

Expression Profile and Gene Regulation Network of NUSAP1 in Pan Cancers Based on Integrated Bioinformatics Analysis.

Background: Nucleolar and spindle-associated protein 1 (NUSAP1) plays key roles in microtubules and chromosomes in normal cells both structurally and functionally. In malignancies, NUSAP1 is frequently dysregulated and mutated. However, the expression profiles and biological functions of NUSAP1 in tumors remain unclear. Methods: NUSAP1 expression in BALB/c mice and human normal or tumor tissues was examined using immunohistochemistry. Kaplan-Meier survival analysis was utilized to assess the prognostic significance of NUSAP1 in tumors, and principal component analysis and co-expression analysis were performed to explore the unique roles of NUSAP1. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed with DAVID. The relevance between NUSAP1 and tumor-infiltrating immune cells was investigated using TIMER. A transcriptional regulation network was constructed using data from The Cancer Genome Atlas. Results: NUSAP1 expression levels in various mice tissues were different. Compared with normal tissues, NUSAP1 was strongly expressed in several human tumor tissues. We believe that NUSAP1 distinctly impacts the prognosis of several cancers and plays various roles in thymoma and testicular germ cell tumors. Further, NUSAP1 expression levels were significantly positively associated with diverse infiltrating levels of immune cells, including B cells, CD4+ and CD8+ T cells, dendritic cells, and macrophages, in thymoma. The expression level of NUSAP1 demonstrated strong relevance with various immune markers in thymoma. Finally, the miR-1236-5p-NUSAP1 and TCF3-NUSAP1 network revealed the tumor-promoting role of NUSAP1 and pertinent underlying mechanisms in human liver hepatocellular carcinoma. Conclusion: NUSAP1 may be regarded as a therapeutic target or potential prognostic biomarker for various cancer types.

Edge-Sharing Octahedrally Coordinated NiFe Dual Active Sites on ZnFe2 O4 for Photoelectrochemical Water Oxidation.

The structural properties of octahedral sites (BOh ) in spinel oxides (AB2 O4 ) play vital roles in the electrochemical performance of oxygen-related reactions. However, the precise manipulation of AB2 O4 remains challenging due to the complexity of their crystal structure. Here, a simple and versatile molten-salt-mediated strategy is reported to introduce Ni2+ in Boh sites intentionally on the surface of zinc ferrite (ZnFe2 O4 , ZFO) to promote the active sites for photoelectrochemical (PEC) water splitting. The as-created photoanode (ZFO-MSNi) shows a remarkable cathodic shift of ≈ 450 mV (turn-on voltage of ≈ 0.6 VRHE ) as well as three times the 1-sun photocurrent density at 1.23 VRHE for PEC water oxidation in comparison with bare ZFO. A comprehensive structural characterization clearly reveals the local structure of the introduced Ni2+ in ZFO-MSNi. Fewer surface trapping states are observed while the precisely introduced Ni2+ and associated neighboring Fe(3-σ)+ (0<σ<1) sites unite in an edge-sharing octahedral configuration to function as NiFe dual active sites for PEC water oxidation. Moreover, open circuit potential measurements and rapid-scan voltammetry investigation give further insight into the enhanced PEC performance. Overall, this work displays a versatile strategy to regulate the surface active sites of photoelectrodes for increasing performance in PEC solar energy conversion systems.

Efficient Exciton Dissociation through the Edge Interfacial State in Metal Halide Perovskite-Based Photocatalysts.

Metal halide perovskites (MHPs) with superior optoelectronic properties have recently been actively pursued as catalysts in heterogeneous photocatalysis. Dissociating excitons into charge carriers holds the key to enhancing the photocatalytic performance of MHP-based photocatalysts, especially for those with strong quantum-confinement effects. However, attaining efficient exciton dissociation has been rather challenging. Herein, we propose a novel concept that the edge interfacial state can trigger anisotropic electron transfer to promote exciton dissociation. By taking Cs4PbBr6/TiO2 mesocrystal heterojunction as a proof-of-concept, we demonstrate that the unique interfacial state at the edge of the system is generated by the defect-mediated chemical interaction and acts as a trap state, which brings on a directionally favored electron transfer from the center to edge regions, thereby significantly enhancing the desired exciton dissociation. Consequently, such a system achieves an excellent performance in photocatalytic CO2 reduction. This paradigmatic work sheds light on the excitonic aspects for rational design of advanced photocatalysts toward high performance.

Afterglow Electrochemiluminescence from Nitrogen-Deficient Graphitic Carbon Nitride.

Almost all current electrochemiluminescent reagents require real-time electrochemical stimulation to emit light. Here, we report a novel electrochemiluminescent reagent, nitrogen-deficient graphitic carbon nitride (CNx), that can emit afterglow electrochemiluminescence (ECL) after cessation of electric excitation. CNx obtained by post-thermal treatment of graphitic carbon nitride (CN) with KSCN has a cyanamide group and a nitrogen vacancy, which created defects to trap electrically injected electrons. The trapped electrons can slowly release and react with coreactants to emit light with longevity. The cathodic afterglow ECL lasts for 70 s after pulsing the CNx nanosheet (CNxNS-1.6)-modified glassy carbon electrode at -1.0 V for 20 s in 2.0 M PBS containing 1 mM K2S2O8. The afterglow ECL mechanism is revealed by investigation of its influencing factors and ECL wavelength. The discovery of afterglow ECL may open a new doorway for new significant applications of the ECL technique and provide a deeper understanding of the structure-property relationships of CN.

Research Progress in the Relationship Between P2X7R and Cervical Cancer.

Cervical cancer is one of the most common and serious tumors in women. Finding new biomarkers and therapeutic targets plays an important role in the diagnosis, prognosis, and treatment of cervical cancer. Purinergic ligand-gated ion channel 7 receptor (P2X7R) is a purine ligand cation channel, activated by adenosine triphosphate (ATP). Studies have shown that P2X7R plays an important role in a variety of diseases and cancers. More and more studies have shown that P2X7R is also closely related to cervical cancer; therefore, the role of P2X7R in the development of cervical cancer deserves further discussion. The expression level of P2X7R in uterine epithelial cancer tissues was lower than that of the corresponding normal tissues. P2X7R plays an important role in the apoptotic process of cervical cancer through various mechanisms of action, and both antagonists and agonists of P2X7R can inhibit the proliferation of cervical cancer cells, while P2X7R is involved in the antitumor effect of Atr-I on cervical cancer cells. This review evaluates the current role of P2X7R in cervical cancer in order to develop more specific therapies for cervical cancer. In conclusion, P2X7R may become a biomarker for cervical cancer screening, and even a new target for clinical treatment of cervical cancer.

PB@PDA nanocomposites as nanolabels and signal reporters for separate-type cathodic photoelectrochemical immunosensors in the detection of carcinoembryonic antigens.

Photoelectrochemical (PEC) immunoassays exhibiting high sensitivity and decent operability have considerable potential in areas such as cancer diagnostics. In particular, cathodic PEC configurations can prevent interference from reductive substances, which can occur in biological samples; however, challenges remain in terms of sensitivity and operability. In this study, separate-type PEC immunoassays were developed for carcinoembryonic antigen (CEA) by combining microplate-based immune recognition and off-on cathodic PEC detection. Polydopamine (PDA)-coated Prussian blue (PB) nanoparticles (PB@PDA NPs) were used as signal tags to label the detection antibody. The PB NPs and PDA captured on the microplates both disassembled under strongly alkaline conditions to generate redox-active electron acceptors. The disassembled products were quantitatively transferred to PEC detection cells and synergistically enhanced the PEC current with microstructured BiOI, which operated as a cathodic semiconductor electrode. As proof of principle, carcinoembryonic antigen (CEA) was applied to elucidate the potential application of PEC immunoassay in clinical diagnosis, and the obtained linear range of the sensor was 0.001-100 ng mL-1 with the detection limit of 54.9 fg mL-1 (S/N = 3). The proposed separate-type off-on PEC strategy showed high sensitivity and decent operability for CEA detection, indicating its potential for the identification of other tumor markers.

LATPS, a novel prognostic signature based on tumor microenvironment of lung adenocarcinoma to better predict survival and immunotherapy response.

Background: Clinically, only a minority of patients benefit from immunotherapy and few efficient biomarkers have been identified to distinguish patients who would respond to immunotherapy. The tumor microenvironment (TME) is reported to contribute to immunotherapy response, but details remain unknown. We aimed to construct a prognostic model based on the TME of lung adenocarcinoma (LUAD) to predict the prognosis and immunotherapy efficacy. Methods: We integrated computational algorithms to describe the immune infiltrative landscape of LUAD patients. With the least absolute shrinkage and selection operator (LASSO) and Cox regression analyses, we developed a LUAD tumor microenvironment prognostic signature (LATPS). Subsequently, the immune characteristics and the benefit of immunotherapy in LATPS-defined subgroups were analyzed. RNA sequencing of tumor samples from 28 lung cancer patients treated with anti-PD-1 therapy was conducted to verify the predictive value of the LATPS. Results: We constructed the LATPS grounded on four genes, including UBE2T, KRT6A, IRX2, and CD3D. The LATPS-low subgroup had a better overall survival (OS) and tended to have a hot immune phenotype, which was characterized by an elevated abundance of immune cell infiltration and increased activity of immune-related pathways. Additionally, tumor immune dysfunction and exclusion (TIDE) score was markedly decreased in the LATPS-low subgroup, indicating an enhanced opportunity to benefit from immunotherapy. Survival analysis in 28 advanced lung cancer patients treated with an anti-PD-1 regimen at Nanfang hospital revealed that the LATPS-low subgroup had better immunotherapy benefit. Conclusion: LATPS is an effective predictor to distinguish survival, immune characteristics, and immunotherapy benefit in LUAD patients.

Unpaired Electron Engineering Enables Efficient and Selective Photocatalytic CO2 Reduction to CH4.

The photocatalytic CO2 reduction to CH4 reaction is a long process of proton-coupled charge transfer accompanied by various reaction intermediates. Achieving high CH4 selectivity with satisfactory conversion efficiency therefore remains rather challenging. Herein, we propose a novel strategy of unpaired electron engineering to break through such a demanding bottleneck. By taking TiO2 as a photocatalyst prototype, we prove that unpaired electrons stabilize the key intermediate of CH4 production, i.e., CHO*, via chemical bonding, which converts the endothermic step of CHO* formation to an exothermic process, thereby altering the reaction pathway to selectively produce CH4. Meanwhile, these unpaired electrons generate midgap states to restrict charge recombination by trapping free electrons. As an outcome, such an unpaired electron-engineered TiO2 achieves an electron-consumption rate as high as 28.3 µmol·g-1·h-1 (15.7-fold with respect to normal TiO2) with a 97% CH4 selectivity. This work demonstrates that electron regulation holds great promise in attaining efficient and selective heterogeneous photocatalytic conversion.

Velvet antler polypeptide combined with calcium phosphate coating to protect peripheral nerve cells from oxidative stress.

Functionalizing biomaterial substrates with biological signals shows promise in regulating cell behaviors through mimicking cellular microenvironment. Calcium phosphate (CaP) coating is an excellent carrier for immobilizing biological molecules due to its non-toxicity, good biocompatibility, biodegradability, and favorable affinity to plenty of molecules. In this study, we reported the adhesion, the viability and proliferation behaviors after oxidative stress injury of Schwann cells RSC96 on CaP immobilized with the Velvet Antler Peptide (VAP) isolated from velvet antler through coprecipitation process in modified Dulbecco's phosphate-buffered saline (DPBS) containing VAP. This approach provided well retention of functional molecules up to 28 days, and supported the adhesion and proliferation of RSC96 after oxidative stress injury without cytotoxicity. The simple and reproducible method of coprecipitation suggests that CaP is an ideal carrier to functionalize materials with biological molecules for peripheral nerve repair-related applications.

ATP-gated P2X7 receptor as a potential target for prostate cancer.

Prostate cancer is the most common malignancy of the male genitourinary system and is one of the leading causes of male cancer death. The P2X7 receptor is an important member of purine receptor family. It is a gated ion channel with adenosine triphosphate (ATP) as the ligand, which exists in a variety of immune tissues and cells and can be involved in tumorigenesis and tumor progression. Studies have shown that the P2X7 receptor is abnormally expressed in prostate cancer, and is related to the level of prostate-specific antigen, P2X7 receptor may be an early biomarker of prostate cancer. The P2X7 receptor is essential in the occurrence and development of prostate cancer. The P2X7 receptor mainly affects the invasion and metastasis of prostate cancer cells through epithelial mesenchymal transition/invasion-related genes and the PI3K/AKT and ERK1/2 signaling pathways. The P2X7 receptor could be a promising therapeutic target for prostate cancer.

Development of Lipo-γ-AA Peptides as Potent Antifungal Agents.

The emergence of drug-resistant fungal pathogens poses great threats to an increasing number of vulnerable populations worldwide, and the need for novel antifungal agents is imperative. In this work, a series of lipo-γ-AA peptides were synthesized and evaluated for their biological activities. One lead, MW5, exhibited potent and broad-spectrum antifungal activity. In addition, MW5 potently boosted the efficacy of fluconazole against clinical azole-resistant Candida isolates. Mechanistic investigation showed that the lead compound disrupted the cell membrane, significantly boosted the production of reactive oxygen species, and undermined the function of the efflux pump, thus resensitizing drug-resistant Candida albicans to fluconazole. Notably, coadministration of MW5 and fluconazole exhibited potent in vivo antifungal activity in a murine model of mucocutaneous candidiasis. Our results demonstrated that lipo-γ-AA peptides have great promise for use alone or in combination to combat drug-resistant Candida infections.

SFTPA1 is a potential prognostic biomarker correlated with immune cell infiltration and response to immunotherapy in lung adenocarcinoma.

Pulmonary surfactant protein A1 (SFTPA1) is a member of the C-type lectin subfamily that plays a critical role in maintaining lung tissue homeostasis and the innate immune response. SFTPA1 disruption can cause several acute or chronic lung diseases, including lung cancer. However, little research has been performed to associate SFTPA1 with immune cell infiltration and the response to immunotherapy in lung cancer. The findings of our study describe the SFTPA1 expression profile in multiple databases and was validated in BALB/c mice, human tumor tissues, and paired normal tissues using an immunohistochemistry assay. High SFTPA1 mRNA expression was associated with a favorable prognosis through a survival analysis in lung adenocarcinoma (LUAD) samples from TCGA. Further GeneOntology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that SFTPA1 was involved in the toll-like receptor signaling pathway. An immune infiltration analysis clarified that high SFTPA1 expression was associated with an increased number of M1 macrophages, CD8+ T cells, memory activated CD4+ T cells, regulatory T cells, as well as a reduced number of M2 macrophages. Our clinical data suggest that SFTPA1 may serve as a biomarker for predicting a favorable response to immunotherapy for patients with LUAD. Collectively, our study extends the expression profile and potential regulatory pathways of SFTPA1 and may provide a potential biomarker for establishing novel preventive and therapeutic strategies for lung adenocarcinoma.

Analysis of Influencing Factors of Repair Effect after Peripheral Nerve Injury.

In order to improve the repair effect after peripheral nerve injury, this paper analyzes the related influencing factors. The regeneration of peripheral nerve includes two continuous and overlapping processes: the acute wound healing period and the axon seeking target tissue period. The complete and effective process of peripheral nerve regeneration includes the sprouting, growth and extension of regenerated axons, and the reconstruction of synaptic connections (neuromuscular junctions) with target organs to realize the reinnervation of nerves and restore function. This process includes three indicators of success in regeneration: structural reconstruction, metabolic regeneration, and functional recovery. In order to improve the repair effect of peripheral nerve injury, relevant influencing factors can be analyzed, and effective improvement of these influencing factors can improve the recovery effect of peripheral nerve injury. Finally, this paper analyzes multiple factors to provide theoretical references for follow-up clinical diagnosis and treatment.

Using the Newcomb-Benford law to study the association between a country's COVID-19 reporting accuracy and its development.

The COVID-19 pandemic has spurred controversies related to whether countries manipulate reported data for political gains. We study the association between accuracy of reported COVID-19 data and developmental indicators. We use the Newcomb-Benford law (NBL) to gauge data accuracy. We run an OLS regression of an index constructed from developmental indicators (democracy level, gross domestic product per capita, healthcare expenditures, and universal healthcare coverage) on goodness-of-fit measures to the NBL. We find that countries with higher values of the developmental index are less likely to deviate from the Newcomb-Benford law. The relationship holds for the cumulative number of reported deaths and total cases but is more pronounced for the death toll. The findings are robust for second-digit tests and for a sub-sample of countries with regional data. The NBL provides a first screening for potential data manipulation during pandemics. Our study indicates that data from autocratic regimes and less developed countries should be treated with more caution. The paper further highlights the importance of independent surveillance data verification projects.

Photodepositing CdS on the Active Cyano Groups Decorated g-C3 N4 in Z-Scheme Manner Promotes Visible-Light-Driven Hydrogen Evolution.

g-C3 N4 /CdS heterojunctions are potential photocatalysts for hydrogen production but their traditional type-II configuration generally leads to weak oxidative and reductive activity. How to construct the novel Z-scheme g-C3 N4 /CdS counterparts to address this issue remains a great challenge in this field. In this work, a new direct Z-scheme heterojunction of defective g-C3 N4 /CdS is designed by introducing cyano groups (NC-) as the active bridge sites. Experimental observations in combination with density functional theory (DFT) calculations reveal that the unique electron-withdrawing feature of cyano groups in the defective g-C3 N4 /CdS heterostructure can endow this photocatalyst with numerous advantageous properties including high light absorption ability, strong redox performance, satisfactory charge separation efficiency, and long lifetime of charge carriers. Consequently, the resultant photocatalytic system exhibits more active performance than CdS and g-C3 N4 under visible light and reaches an excellent hydrogen evolution rate of 1809.07 µmol h-1 g-1 , which is 6.09 times higher than pristine g-C3 N4 . Moreover, the defective g-C3 N4 /CdS photocatalyst maintains good stability after 40 h continuous test. This work provides new insights into design and construction of Z-scheme heterojunctions for regulating the visible-light-induced photocatalytic activity for H2 evolution.

Anatomy-based application of finger fascia pedicled skin artery branches flap.

OBJECTIVES: To study the anatomy of the dorsal metacarpal arteries and their branches, to understand the positions and shapes of the arteries and their branches, and to observe the capillary network formed on the lateral and the dorsal sides of the finger under a microscope. Based on this anatomy, a finger fascia pedicled skin artery branch flap was designed to repair fingertip wounds. METHODS: A total of 5 fresh adult cadaveric hand specimens were infused with red latex. The anatomy of the dorsal finger intrinsic arteries of the 40 fingers (excluding the thumbs) were observed under a microscope, and a capillary network was formed on the lateral and the dorsal sides of the fingers. Then, 10 cases of finger soft tissue defects were repaired using an anatomy-based design finger fascia pedicled skin artery branch flap. RESULTS: The anatomical observations indicated that the intrinsic artery on each side of the finger sends four thicker cutaneous branches toward to the dorsal side, wherein the descending branch of the upper cutaneous branch coincides with the ascending branch of the next cutaneous branch to form a lateral vascular chain. A fascia flap pedicled (>0.5 cm) skin artery branch flap was used to repair the patients' finger injuries (8 males and 2 females, aged 21 to 52 years). The wound surface ranges were about 2.8 cm × 1.9, and the flap ranges were about 3 cm × 2.1 cm. During the 5-12 months of follow-up, all the flaps survived well. CONCLUSION: The bilateral finger arteries emit a number of macroscopically identifiable capillary branches and form a capillary network using anastomosis between the cutaneous branches. The finger fascia pedicled skin artery branches flap, not <0.5 cm wide, contains the capillary branch of the dorsal finger artery as the flap for the blood supply. The flap can cover various types of distal finger wounds.

P2X7 receptor: a critical regulator and potential target for breast cancer.

Breast cancer is currently the most common cancer and the leading cause of cancer death among women worldwide. Advanced breast cancer is prone to metastasis, and there is currently no drug to cure metastatic breast cancer. The purinergic ligand-gated ion channel 7 receptor is an ATP-gated nonselective cation channel receptor and is involved in signal transduction, growth regulation, cytokine secretion, and tumor cell development. Recent studies have shown that upregulation of the P2X7 receptor in breast cancer can mediate AKT signaling pathways, Ca2 þ-activated SK3 potassium channels, and EMT and regulate the secretion of small extracellular vesicles to promote breast cancer invasion and migration, which are affected by factors such as hypoxia and ATP. In addition, studies have shown that microRNAs can bind to the 3' untranslated region of the P2X7 receptor, which affects the occurrence and development of breast cancer by upregulating and downregulating P2X7 receptor expression. Studies have shown that new P2X7 receptor inhibitors, such as emodin and Uncaria tomentosa, can inhibit P2X7 receptor-mediated breast cancer invasion and are expected to be used clinically. This article reviews the research progress on the relationship between the P2X7 receptor and breast cancer to provide new ideas and a basis for clinical diagnosis and treatment.

The P2X7 purinergic receptor: a potential therapeutic target for lung cancer.

PURPOSE: Purinergic P2X7 receptor (P2X7R) is a gated ion channel for which adenosine triphosphate (ATP) is a ligand. Activated P2X7R is widely expressed in a variety of immune cells and tissues and is involved in a variety of physiological and pathological processes. Studies have confirmed that P2X7R is involved in the regulation of tumor cell growth, stimulating cell proliferation or inducing apoptosis. Recent studies have found that P2X7R is abnormally expressed in lung cancer and is closely related to the carcinogenesis and development of lung cancer. In this paper, we comprehensively describe the structure, function, and genetic polymorphisms of P2X7R. In particular, the role and therapeutic potential of P2X7R in lung cancer are discussed to provide new targets and new strategies for the treatment and prognosis of clinical lung cancer. METHODS: The relevant literature on P2X7R and lung cancer from PubMed databases is reviewed in this article. RESULTS: P2X7R regulates the function of lung cancer cells by activating multiple intracellular signaling pathways (such as the JNK, Rho, HMGB1 and EMT pathways), thereby affecting cell survival, growth, invasion, and metastasis and patient prognosis. Targeting P2X7R with inhibitors effectively suppresses the growth and metastasis of lung cancer cells. CONCLUSION: In summary, P2X7R is expected to become a potential target for the treatment of lung cancer, and more clinical research is needed in the future to explore the effectiveness of P2X7R antagonists as treatments.