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The aim of this study was to find new protein biomarkers that could be used to detect hepatocellular carcinoma (HCC) in the serum. We identified 11 proteins in the tissue that could be used to classify samples from HCC and control subjects. The 11 identified tissue biomarkers were combined with 10 commonly used serum HCC biomarkers for further verification in a large number of serum samples from HCC patients and healthy controls. 17 of the 21 prospective serum biomarkers were determined to be differentially expressed through collinearity and significance analysis. Through the method of supervised learning, a random forest model was constructed to reduce the dimensionality of the number of differentially expressed proteins, and finally, 4 differentially expressed proteins were identified: AFP, GDF15, CEACAM-1, and MMP-9, and suggested to have potential application in clinical diagnosis of HCC.

Palladium(0) as one of the vital transition metals, is employed in numerous industries, such as drug synthesis, aerospace high-tech field and automobile industry. When the Pd(0) enter into the body, it will bind with thiol-containing amino acids, DNA, RNA, and other biomolecules damaging to human health. Thus, developing a novel tool for monitoring and imaging of Pd(0) in vivo is very urgent. In the work, based on a intramolecular charge transfer (ICT) mechanism a two-photon fluorescent probe NIPd had been designed and synthesized for the recognition Pd(0). In vitro experiments data displayed that probe NIPd exhibited a 13-fold fluorescent increase for Pd(0) in 30 min in the aqueous solution with a detection limit of 16 nmol/L. It also showed the outstanding selectivity and antijamming performance. More importantly, NIPd could be served as a two-photon fluorescent probe for real-time monitoring Pd(0) in living cells and mice.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has become a worldwide pandemic, and there is a pressing need for the rapid development of novel therapeutic strategies. SARS-CoV-2 viral entry is mediated by interaction between the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein and host cellular receptor, human angiotensin converting enzyme 2 (ACE2). The lack of a high throughput screening (HTS) platform for candidate drug screening means that no targeted COVID-19 treatments have been developed to date. To overcome this limitation, we developed a novel, rapid, simple, and HTS binding assay platform to screen potential inhibitors of the RBD-ACE2 complex. Three "neutralizing" mouse monoclonal antibodies capable of blocking the RBD-ACE2 interaction were identified using our binding assay and pseudovirus neutralization assay followed by further validation with the Focus Reduction Neutralization Test (FRNT), which analyzes the neutralization capacity of samples in the presence of live SARS-CoV-2. Furthermore, the consistency of our binding assay and FRNT results (R

The Wnt pathway is dysregulated and activated in many human malignancies. More than 90% of colon cancers have variations in the Wnt pathway. Sulindac, a drug that targets protein Dvl of the Wnt/Dvl/β-catenin pathway, which regulates cancer gene expression, has been reported to significantly reduce the incidence and the risk of death from colorectal cancer and other types of cancer. Herein, a dual functional compound (SLN) containing Sulindac and a linked fluorophore is first reported, combining the functions of lighting up colon cancer cells as a flare and inhibiting colon tumors as a drug. SLN can not only mark the Dvl protein in the Wnt pathway to recognize tumors layer by layer but also achieve effective inhibition of colon cancer, providing a promising reagent for chemotherapy and a fluorescent indicator for surgery during the removal the colon tumors in situ.

The piezoelectric polymer poly(vinylidene fluoride) (PVDF) has been widely employed for energy harvesting or sensors. Its piezoelectricity originates from the unique crystal structure and the oriented electric dipoles. Generally, electrospinning (ES) is able to improve the crystallinity and piezoelectricity of PVDF. In this investigation, three types of ES, including far-field ES with random (R-PVDF-FFES) or aligned distribution (A-PVDF-FFES) and near-field ES (PVDF-NFES), are applied to fabricate a one-step polarized PVDF membrane. To compare the piezoelectricity of separated PVDF-NFES fibers, the array of PVDF-NFES fibers is encapsulated in polylactic acid (PLA). The result shows that the piezoelectricity of PVDF is dramatically enhanced by NFES and FFES. In d31 mode, the current density of PVDF-NFES-PLA is 75.63 pA cm-2 with a 2 Hz shear force, which is four times larger than A-PVDF-FFES (17.62 pA cm-2) or seven times larger than R-PVDF-FFES (10.63 pA cm-2). Due to its outstanding property, the PVDF-NFES-PLA membrane is designed to be applied as a self-powered device. The unimorph cantilevers are prepared to harvest the vibration energy and their output power density reaches 95.3 μW m-2 at a resonance frequency of 31 Hz. Meanwhile, the flexible bending sensor and pressure sensor are fabricated with a PVDF-NFES-PLA membrane, which shows the stable response for pressure with sensitivity values of 864.68 and 22.6 mV kPa-1, respectively.

Sensors capable of monitoring dynamic mechanics of tendons throughout a body in real time could bring systematic information about a human body’s physical condition, which is beneficial for avoiding muscle injury, checking hereditary muscle atrophy, and so on. However, the development of such sensors has been hindered by the requirement of superior portability, high resolution, and superb conformability. Here, we present a wearable and stretchable bioelectronic patch for detecting tendon activities. It is made up of a piezoelectric material, systematically optimized from architectures and mechanics, and exhibits a high resolution of 5.8 × 10 − 5 N with a linearity parameter of R 2 = 0.999 . Additionally, a tendon real-time monitoring and healthcare system is established by integrating the patch with a micro controller unit (MCU), which is able to process collected data and deliver feedback for exercise evaluation. Specifically, through the patch on the ankle, we measured the maximum force on the Achilles tendon during jumping which is about 16312 N, which is much higher than that during normal walking (3208 N) and running (5909 N). This work not only provides a strategy for facile monitoring of the variation of the tendon throughout the body but also throws light on the profound comprehension of human activities.

Cyclooxygenase-2 (COX-2) is an enzyme overexpressed in most types of cancers and has been used for an excellent targetable biomarker. Celecoxib is an effective inhibitor of COX-2, used in anti-inflammation. Herein we report a one and two-photon fluorescence probe (NP-C6-CXB) for COX-2, based on the conjugation of naphthalamide with Celecoxib, by using flexible hexylene linker. NP-C6-CXB is nonfluorescent in buffer solution and normal cells, while it shows bright fluorescence in solutions and cancer cells in the presence of COX-2 with an excellent selectivity. Interestingly, NP-C6-CXB can discriminate cancer cells (MCF-7) from normal cells (COS-7) in the single culture medium under confocal microscopy. Due to the selective binding affinity of NP-C6-CXB with a COX-2 enzyme, the intensity is proportional to the level of COX-2 enzyme in cancer cells. In vivo and in vitro experiments proved that NP-C6-CXB is a potential tool for identification of tumor and might be used in surgical resection of COX-2 expressed tumors.

Hepatocellular carcinoma (HCC) is the major subtype of primary liver cancer. Although the standard treatment method based on surgery has generally extended life, it still causes the second and sixth most prevalent cancer-related death in men and women, respectively. The recurrence of cancer caused by unclear resection margins and any remaining undiscovered metastatic nodules should take a large proportion of responsibility for the poor prognosis after resective surgery. Therefore, a practical and effective method that can be used during hepatectomy to specifically identify HCC is a potentially significant area deserving attention. Tests involving fluorescence have been used in many biological systems. In this study, we use a probe that can combine with cyclooxygenase-2 (COX-2) and subsequently emit fluorescence to identify HCC cells and heteroplastic tumors in a mouse model. The results show that this specific probe can clearly differentiate HCC, with differences that could be observed with the naked eye in human samples. The biotechnology of knocking down COX-2 and its inhibitor were used on human HCC cell line SMMC7721, and the outcomes confirmed the above results. The toxic effect also showed that the probe had no harmful effect on normal liver cells. Taken together, our study demonstrates that a COX-2-specific fluorescence probe may be a new and effective method to identify HCC, especially during surgery.

The integration of precise detection, long-term prevention and effective treatment are beneficial to monitor cancer bioactivity and prevent malignant metastasis for breast cancer patients. Herein, a novel fluorescence probe (IBLN) is designed and synthesized which contains a fluorophore (naphthalimide), a linker and a non-steroidal anti-inflammatory drug (ibuprofen). The specific optical imaging, prevention and treatment effects of breast cancer are relied on the introduction of a powerful cyclooxygenase-2-specific inhibitor, ibuprofen, which makes IBLN possible to successfully differentiate breast cancer cells from normal cells. In addition, fluorescent cellular imaging agent naphthalimide also has anticancer effects via inducing lysosomal membrane permeabilization (LMP). The multi-functional ibuprofen-derived fluorescence inhibitor IBLN realizes the imaging, prevention and treatment for breast cancer, which the selectivity and anticancer effects would be strengthened compared to the single naphthalimide or ibuprofen. Therefore, we envisage that the multi-function strategy in IBLN would be attractive way to explore potential reagent for fluorescence-visible breast cancer therapy in situ.

Combining imaging and treatment of cancer into one molecule has become an efficient strategy for studies on pathology and cancer therapeutics. Herein, a novel highly selective and sensitive green-emitting probe (APLN), which contained a fluorophore (Naphthalimide), a linker, and a COX-2 kinase inhibitor (aspirin) has been designed and evaluated. Cyclooxygenase-2 (COX-2), as one of the typical rate-limiting enzymes, has been utilized as imaging and therapeutic target since this enzyme is overexpressed in various cancer cell lines. Aspirin, a non-steroidal anti-inflammatory drug (NSAID), has been reported to reduce the incidence and risk of cancers by down-regulating the expression of COX-2 in cancer cells. The APLN probe has been proved to successfully label the COX-2 enzyme to identify tumors and significantly inhibit tumor growth in a xenotransplantation model of nude mice. Therefore, this enzyme-targeted fluorescence probe (APLN) is a potential reagent for in situ imaging and fluorescent-visible cancer therapy.

We report a highly selective and sensitive fluorescent probe (FP) for detecting fluoride ions, for the first time, lighting up the fluoride ions in mitochondria with a strong green fluorescence. FP could be easily prepared as fluoride paper test strips to detect fluoride ions in aqueous solutions with a detection limit as low as 19 ppb.

Topotecan (TPT), a semisynthetic derivative of camptothecin, has been used in cancer chemotherapy, but side effects and drug resistance limit its clinical application. Daidzein (DAI), a natural isoflavone and bioactive food component widely existing in fruits, nuts, soybeans and soy-based products, is a type of phytoestrogen. Combination treatment with DAI and TPT showed a strong synergistic effect on tumor cells, with a 0.10˜0.66 combined index, by increasing TPT inhibition on Topo Ⅰ, resulting in more cells arresting at the G2/M phase and inducing more cells to undergo apoptosis. In addition, the resistance of MCF7/ADR cells to TPT was reversed (the resistance index decreased from 7.17 to 0.77) by inhibiting the expression of ERα and BCRP to increase TPT accumulation intracellularly. Moreover, the combination of DAI and TPT showed a stronger inhibitory effect (P 0.01) on tumor growth in both MCF7 and MCF7/ADR xenograft models than the 9 mg/kg TPT monotherapy group. Our results may provide a reasonable, new approach to develop safe and efficient nutrition components from foods for breast cancer combination treatment.

Identifying cancer cells and quantifying cancer-related events in particular organelles in a rapid and sensitive fashion are important for early diagnosis and for studies on pathology and therapeutics of cancers. Herein a smart "off-on" cyclooxygenase-2-specific fluorescence probe (ANQ-IMC-6), able to report the presence of cancer cells and to image Golgi-related events, has been designed and evaluated. Cyclooxygenase-2 (COX-2) has been used as imaging target in the probe design, since this enzyme is a biomarker of virtually all cancer cell lines. In the free state in aqueous solution, ANQ-IMC-6 mainly exists in a folded conformation where probe fluorescence is quenched through photoinduced electron transfer between the fluorophore acenaphtho[1,2-b]quinoxaline (ANQ) and the recognition group, indomethacin (IMC). Fluorescence is turned on, by restraining the photoinduced electron transfer, when ANQ-IMC-6 is forced to adopt the unfolded state following binding to COX-2 in the Golgi apparatus of cancer cells. ANQ-IMC-6 provides high signal-to-background staining and has been successfully used to rapidly differentiate cancer cells from normal cells when using flow cytometry and one- and two-photon fluorescence microscopic imaging. Furthermore, ANQ-IMC-6 may be able to visualize dynamic changes of the Golgi apparatus during cancer cell apoptosis, with possible application to early diagnosis.

In this work, a rapid model is established to study the effects of flexoelectricity and surface elasticity on the piezoelectric potential of a bent ZnO nanowire. Based on the piezoelectric theory and core-surface model, the distribution of piezoelectric potential of the ZnO nanowire is investigated. The analytical solution shows that the flexoelectricity and surface elasticity both significantly influence the piezoelectric potential. However, the effect of flexoelectricity is longitudinal dependent, which vanishes on the top side of nanowire, but only left surface elasticity effect on the potential. Simulation results show that the maximum value of potential on the top side of nanowire is about ± 220.5mV, of which result is lower compared to other theoretical models, but it should be more reasonable.

Two novel fluorene-derived two-photon fluorescent probes (TPFL) targeting the endoplasmic reticulum (TPFL-ER) and lysosomes (TPFL-Lyso) were synthesized by introducing a chlorine group and a morpholine group, respectively. They were shown to be suitable for specific and simultaneous imaging of the endoplasmic reticulum and lysosomes without affecting protein movements owing to their similar molecular structures. TPFL-ER and TPFL-Lyso were successfully used to visualize the changes of the endoplasmic reticulum and lysosomes during cancer cell apoptosis and they demonstrated high specificity and sensitivity, excellent photostability, and low phototoxicity.