Hu, Wenjun

Chen Y., Yang Y., Zhou H., Yao W., Zeng S., Chen M., Hu W., Liu G.L., Huang L.

Li P., Que Y., Wong C., Lin Y., Qiu J., Gao B., Zhou H., Hu W., Shi H., Peng Y., Huang D., Gao W., Qiu X., Liang A.

Li P., Que Y., Wong C., Lin Y., Qiu J., Gao B., Zhou H., Hu W., Shi H., Peng Y., Huang D., Gao W., Qiu X., Liang A.

Extracellular matrix (ECM) metabolism disorders in the inflammatory microenvironment play a key role in the pathogenesis of intervertebral disc degeneration (IDD). Interleukin-32 (IL-32) has been reported to be involved in the progression of various inflammatory diseases; however, it remains unclear whether it participates in the matrix metabolism of nucleus pulposus (NP) cells. Therefore, this study aimed to investigate the mechanism of IL-32 on regulating the ECM metabolism in the inflammatory microenvironment. RNA-seq was used to identify aberrantly expressed genes in NP cells in the inflammatory microenvironment. Western blotting, real-time quantitative PCR, immunohistochemistry and immunofluorescence analysis were performed to measure the expression of IL-32 and metabolic markers in human NP tissues or NP cells treated with or without tumor necrosis factor-α (TNF-α). In vivo, an adeno-associated virus overexpressing IL-32 was injected into the caudal intervertebral discs of rats to assess its effect on IDD. Proteins interacting with IL-32 were identified via immunoprecipitation and mass spectrometry. Lentivirus overexpressing IL-32 or knocking down Fat atypical cadherin 4 (FAT4), yes-associated protein (YAP) inhibitor-Verteporfin (VP) were used to treat human NP cells, to explore the pathogenesis of IL-32. Hippo/YAP signaling activity was verified in human NP tissues. IL-32 expression was significantly upregulated in degenerative NP tissues, as indicated in the clinical samples. Furthermore, IL-32 was remarkably overexpressed in TNF-α-induced degenerative NP cells. IL-32 overexpression induced IDD progression in the rat model. Mechanistically, the elevation of IL-32 in the inflammatory microenvironment enhanced its interactions with FAT4 and mammalian sterile 20-like kinase1/2 (MST1/2) proteins, prompting MST1/2 phosphorylation, and activating the Hippo/YAP signaling pathway, causing matrix metabolism disorder in NP cells. Our results suggest that IL-32 mediates matrix metabolism disorders in NP cells in the inflammatory micro-environment via the FAT4/MST/YAP axis, providing a theoretical basis for the precise treatment of IDD.

Fan H., Chen M., Li R., Chen Y., Zeng S., Hu W., Liu G.L., Sun C., Huang L.

Liang J., Qin Y., Yang Y., Song Z., Li Y., Liu G.L., Hu W.

Dong Z., Zhang Q., Zhang Q., Hu W., Yan L., Peng F., Hu Z., Tangthianchaichana J., Zhao Y., Du S., Lu Y.

Chen M., Fan H., Li W., Ruan J., Yang Y., Mao C., Li R., Liu G.L., Hu W.

AbstractConsidering the improved detection of biological analytes for affinity analysis is highly desirable, a metasurface plasmon resonance (Meta‐SPR)‐based imaging system, incorporating a localized SPR sensing platform with different microfluidic systems and employing simple bright‐field imaging, is established in this study. This system enables low‐level analyte concentration analysis, ranging from 100 pm to 100 nm, with the real‐time removal of nonspecific binding signals within the same device field of view. Combined with microfluidic systems and microdroplet spotting, it is possible to automatically measure the kinetic curves of a sample at ten concentration gradients or detect the specific responses of multiple samples in a single experiment simultaneously. This system can inexpensively and conveniently achieve complex detection functions, demonstrating an innovative breakthrough in sensor detection.

Fan H., Li R., Chen Y., Zhang H., Zeng S., Ji W., Hu W., Yin S., Li Y., Liu G.L., Huang L.

The accumulation of trace amounts of certain small molecules in food poses considerable human health challenges, including the potential for carcinogenesis and mutagenesis. Here, an ultrasensitive gold-platinum nanoflower-coupled metasurface plasmon resonance (MetaSPR) (APNMSPR) biosensor, based on a competitive immunoassay, was developed for the multiplexed and rapid quantitative analysis of trace small molecules in eggs, offering timely monitoring of food safety. This one-step biosensor can be integrated into either a newly designed detachable high-throughput MetaSPR chip-strip plate device or a standard 96-well plate for multiplexed small-molecule detection within a single egg. The limits of detection were 0.81, 1.12, and 1.74 ppt for florfenicol, fipronil, and enrofloxacin, respectively, demonstrating up to 1000-fold increased sensitivity and a 15-fold reduction in analysis time compared with those of traditional methods. The results obtained using the APNMSPR biosensor showed a strong correlation with those obtained using liquid chromatography-tandem mass spectrometry. The APNMSPR biosensor holds immense promise for the multiplexed, highly sensitive, and rapid quantitative analysis of small molecules for applications in food safety control, early diagnosis, and environmental monitoring.

Wang Y., Wang G., Hu S., Yin C., Zhao P., Zhou X., Shao S., Liu R., Hu W., Liu G.L., Ke W., Song Z.

Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality. Human phenylalanine tRNA synthetase (PheRS) comprises two α catalytic subunits encoded by the FARSA gene and two β regulatory subunits encoded by the FARSB gene. FARSB is a potential oncogene, but no experimental data show the relationship between FARSB and HCC progression. We found that the high expression of FARSB in liver cancer is closely related to patients’ low survival and poor prognosis. In liver cancer cells, the mRNA and protein expression levels of FARSB are increased and promote cell proliferation and migration. Mechanistically, FARSB activates the mTOR complex 1 (mTORC1) signaling pathway by binding to the component Raptor of the mTORC1 complex to play a role in promoting cancer. In addition, we found that FARSB can inhibit erastin-induced ferroptosis by regulating the mTOR signaling pathway, which may be another mechanism by which FARSB promotes HCC progression. In summary, FARSB promotes HCC progression and is associated with the poor prognosis of patients. FARSB is expected to be a biomarker for early screening and treatment of HCC.

Liu R., Yin C., Zhao P., Guo B., Ke W., Zheng X., Xie D., Wang Y., Wang G., Jia Y., Gao Y., Hu W., Liu G.L., Song Z.

Abstract Background Nuclear respiratory factor 1 (NRF1) is a transcription factor that participates in several kinds of tumor, but its role in hepatocellular carcinoma (HCC) remains elusive. This study aims to explore the role of NRF1 in HCC progression and investigate the underlying mechanisms. Results NRF1 was overexpressed and hyperactive in HCC tissue and cell lines and high expression of NRF1 indicated unfavorable prognosis of HCC patients. NRF1 promoted proliferation, migration and invasion of HCC cells both in vitro and in vivo. Mechanistically, NRF1 activated ERK1/2-CREB signaling pathway by transactivating lysophosphatidylcholine acyltransferase 1 (LPCAT1), thus promoting cell cycle progression and epithelial mesenchymal transition (EMT) of HCC cells. Meanwhile, LPCAT1 upregulated the expression of NRF1 by activating ERK1/2-CREB signaling pathway, forming a positive feedback loop. Conclusions NRF1 is overexpressed in HCC and promotes HCC progression by activating LPCAT1-ERK1/2-CREB axis. NRF1 is a promising therapeutic target for HCC patients.

Li R., Fan H., Zhou H., Chen Y., Yu Q., Hu W., Liu G.L., Huang L.

AbstractDeveloping plasmonic biosensors that are low‐cost, portable, and relatively simple to operate remains challenging. Herein, a novel metasurface plasmon‐etch immunosensor is described, namely a nanozyme‐linked immunosorbent surface plasmon resonance biosensor, for the ultrasensitive and specific detection of cancer biomarkers. Gold‐silver composite nano cup array metasurface plasmon resonance chip and artificial nanozyme‐labeled antibody are used in two‐way sandwich analyte detection. Changes in the biosensor's absorption spectrum are measured before and after chip surface etching, which can be applied to immunoassays without requiring separation or amplification. The device achieved a limit of alpha‐fetoprotein (AFP) detection < 21.74 fM, three orders of magnitude lower than that of commercial enzyme‐linked immunosorbent assay kits. Additionally, carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125) are used for quantitative detection to verify the universality of the platform. More importantly, the accuracy of the platform is verified using 60 clinical samples; compared with the hospital results, the three biomarkers achieve high sensitivity (CEA: 95.7%; CA125: 90.9%; AFP: 86.7%) and specificity (CEA: 97.3%; CA125: 93.9%; AFP: 97.8%). Due to its rapidity, ease of use, and high throughput, the platform has the potential for high‐throughput rapid detection to facilitate cancer screening or early diagnostic testing in biosensing.

Jia Y., Yin C., Ke W., Liu J., Guo B., Wang X., Zhao P., Hu S., Zhang C., Li X., Liu R., Zheng X., Wang Y., Wang G., Pan H., et. al.

The threat to public health posed by rapidly increasing levels of cadmium (Cd) in the environment is receiving worldwide attention. Although, Cd is known to be absorbed into the body and causes non-negligible damage to the liver, the detailed mechanisms underlying its hepatoxicity are incompletely understood. In the present study, investigated the effect of TNFAIP3 and α-ketoglutarate (AKG) on Cd-induced liver inflammation and hepatocyte death. Male C57BL/6 mice were exposed to cadmium chloride (1.0 mg/kg) while being fed a diet with 2 % AKG for two weeks. We found that Cd induced hepatocyte injury and inflammatory infiltration. In addition, TNFAIP3 expression was inhibited in the liver tissues and cells of CdCl2-treated mice. Mouse hepatocyte-specific TNFAIP3 overexpression by tail vein injection of an adeno-associated virus (AAV) vector effectively alleviated Cd-induced hepatic necrosis and inflammation, which was mediated by the NF-κB signaling pathway. Notably, this inhibitory effect of TNFAIP3 on Cd-induced liver injury was dependent on AKG. Exogenous addition of AKG prevented Cd exposure-induced increases in serum ALT, AST and LDH levels, production of pro-inflammatory cytokines, activation of the NF-κB signaling pathway, and even significantly reduced Cd-induced oxidative stress and hepatocyte death. Mechanistically, AKG exerted its anti-inflammatory effect by promoting the hydroxylation and degradation of HIF1A to reduce its Cd-induced overexpression in vivo and in vitro, avoiding the inhibition of the TNFAIP3 promoter by HIF1A. Moreover, the protective effect of AKG was significantly weaker in Cd-treated primary hepatocytes transfected with HIF1A pcDNA. Overall, our results reveal a novel mechanism of Cd-induced hepatotoxicity.

Liu J., Hu X., Hu Y., Chen P., Xu H., Hu W., Zhao Y., Wu P., Liu G.L.

The microRNA21 (miR-21), a specific tumor biomarker, is crucial for the diagnosis of several cancer types, and investigation of its overexpression pattern is important for cancer diagnosis. Herein, we report a low-cost, rapid, ultrasensitive, and convenient biosensing strategy for the detection of miR-21 using a nanoplasmonic array chip coupled with gold nanoparticles (AuNPs). This sensing platform combines the surface plasmon resonance effect of nanoplasmonics (NanoSPR) and the localized surface plasmon resonance (LSPR) effect, which allows the real-time monitoring of the subtle optical density (OD) changes caused by the variations in the dielectric constant in the process of the hybridization of the target miRNA. Using this method, the miRNA achieves a broad detection range from 100 aM to 1 μM, and with a limit of detection (LoD) of 1.85 aM. Furthermore, this assay also has a single-base resolution to discriminate the highly homologous miRNAs. More importantly, this platform has high throughput characteristics (96 samples can be detected simultaneously). This strategy exhibits more than 86.5 times enhancement in terms of sensitivity compared to that of traditional biosensors.

Liu R., Yin C., Zhao P., Guo B., Ke W., Zheng X., Xie D., Wang Y., Wang G., Jia Y., Gao Y., Hu W., Liu G.L., Song Z.

Liu J., Chen P., Hu X., Huang L., Geng Z., Xu H., Hu W., Wang L., Wu P., Liu G.L.

The novel mutations attributed by the high mutagenicity of the SARS-CoV-2 makes its prevention and treatment challenging. Developing an ultra-fast, point-of-care-test (POCT) protocol is critical for responding to large-scale spread of SARS-CoV-2 in public places and in resource-poor remote areas. Here, we developed a nanoplasmonic enhanced isothermal amplification (NanoPEIA) strategy that combines a nanoplasmonic sensor with isothermal amplification. The novel strategy provides an ideal easy-to operate detection platform for obtaining accurate, ultra-fast and high-throughput (96 samples can be tested together) data. For clinical samples with viral detection at Ct value

He T., Li D., Qin Y., Xiang Y., Tang Y., Tian J., Tang Y.

Abdel-Hamied M., Guo M., Wei Y., Bansmann J., El Nashar R.M., Oswald F., Mizaikoff B., Kranz C.

Guo C., He Y., Chen K., Zhang S., Wang M., He L., Zhang Z.

Asif M., Algethami J.S., Alhamami M.A., Lie P., Shaomin S., Aziz A.

Špringer T., Bocková M., Slabý J., Sohrabi F., Čapková M., Homola J.

Yatera K., Nishida C., Mukae H.

Chu S., Yuan H., Liang Y., Yang C., Liu Q., Peng W.

Qin Z., Jiao L., Hu L., Zhang Y., Jia X., Chen C., Sun X., Zhai Y., Zhu Z., Lu X.

AbstractDeveloping efficient peroxidase‐like nanozymes to surpass natural enzymes remains a significant challenge. Herein, an amorphous RuO2 nanozyme with peroxidase‐like activity is synthesized for activating H2O2 with a specific activity of 1492.52 U mg−1, outperforming the crystalline RuO2 nanozymes by a factor of 22 and far superior to natural peroxidases. Amorphous RuO2 nanozymes with long‐range disordered atomic arrangements can effectively elongate the O─O bonds in H2O2. Abundant oxygen vacancies in amorphous RuO2 nanozymes lead to an upshift of the d‐band center, enhancing the exceptional adsorption strength of H2O2, which improve the electron transfer efficiency and ensure superior peroxidase‐like activity. Accordingly, a nanozyme‐linked immunosorbent assay is developed for the precise and sensitive detection of prostate‐specific antigens with a detection limit as low as 0.52 pg mL−1. This study introduces a simple approach for developing high‐performance peroxidase‐like nanozymes to improve the analytical performances of prostate‐specific antigens in clinical diagnostics.

Xu B., Wang J., Xin Y., Chen D., Zhang N., Xue Y., Liu X., Li X., Gao W., Hu Z., Sun T., Liu K., Tian W., Lu Y.

AbstractGold nanoparticles (Au NPs), as a class of functional nanomaterials, have attracted considerable interest for biomedical applications owing to their unique chemical and physical properties. However, colloidal solutions of Au NPs are thermodynamically unstable because of their high surface energy, resulting in poor stability and biocompatibility in physiological environments. Herein, we present a novel strategy for coating Au NPs using in situ polymerization to form a three‐dimensional (3D) network polymer shell around each particle. This approach enables the creation of an ultra‐stable core‐shell structure that effectively improves biocompatibility and stability, even in complex biological environments. The surface characteristics of the polymer shell can also be precisely tailored by carefully selecting the monomers to meet biomedical application requirements. These properties enable prolonged circulation within the bloodstream and enhanced tumor targeting in mice. This strategy offers an ultra‐stable, aqueous‐based, and biocompatible polymer shell for Au NPs, paving the way for the surface modification of gold nanomaterials in biomedical applications.

Xu B., Wang J., Xin Y., Chen D., Zhang N., Xue Y., Liu X., Li X., Gao W., Hu Z., Sun T., Liu K., Tian W., Lu Y.

AbstractGold nanoparticles (Au NPs), as a class of functional nanomaterials, have attracted considerable interest for biomedical applications owing to their unique chemical and physical properties. However, colloidal solutions of Au NPs are thermodynamically unstable because of their high surface energy, resulting in poor stability and biocompatibility in physiological environments. Herein, we present a novel strategy for coating Au NPs using in situ polymerization to form a three‐dimensional (3D) network polymer shell around each particle. This approach enables the creation of an ultra‐stable core‐shell structure that effectively improves biocompatibility and stability, even in complex biological environments. The surface characteristics of the polymer shell can also be precisely tailored by carefully selecting the monomers to meet biomedical application requirements. These properties enable prolonged circulation within the bloodstream and enhanced tumor targeting in mice. This strategy offers an ultra‐stable, aqueous‐based, and biocompatible polymer shell for Au NPs, paving the way for the surface modification of gold nanomaterials in biomedical applications.

Wei H., Wang S., Wang S., Xiao W., Ding A., Deng N., Wang H.

Kamal Eddin F.B., Fan H., Liu Z., Donati P., Amin Y., Fen Y.W., Liang J., Pompa P.P., He S.

AbstractIn today's technologically advanced era, the demand for swift and precise analyses spans scientific research and industrial applications alike. Surface plasmon resonance (SPR) technology has surged in popularity, due to its real‐time measurement capabilities with exceptional sensitivity and label‐free operation. These attributes have propelled SPR into prominence across diverse fields including medical diagnostics, pharmaceuticals, food safety, and environmental monitoring of hazardous compounds. Here the key principles behind SPR are delved, and the workings of SPR‐based sensors are elucidated. Additionally, the latest advancements in SPR biosensors tailored for detecting a variety of analytes, with a focus on dopamine (DA) and α‐synuclein, which hold particular significance in the context of neurological disorders, are examined. Here potential breakthroughs of SPR technology are discussed, thanks to the integration with nanomaterials, lab‐on‐a‐chip devices, multiplexing formats, and machine learning. Finally, new resonance modes are discussed based on subwavelength structures leveraging guided mode resonance (GMR), surface lattice resonance (SLR), and bound state in the continuum (BIC) mode resonance and their potential applications, particularly in nonplasmonic refractive index biosensors.

N K A., R L., K V., Al-Zahrani F.A.

Zhang Z., Chen Y., Zhao M., Lv Y., Wang Y., Yang L., Ye P., Fang Y., Kang X., Li X., Zhang L., Ge W., Du W.

Wang X., Li S., Chen J., Liu L., Li F.

As an endogenous metabolite, α-ketoglutarate (AKG) exhibits potent antioxidant properties, yet its molecular mechanisms remain unclear. Dermal Papilla Cells (DPCs), functioning as the regulatory hub of hair follicle morphogenesis, serve as a pivotal model system for deciphering follicular functionality and regeneration mechanisms through their orchestration of signaling networks. Using a hydrogen peroxide (H2O2)-induced oxidative stress model in DPCs, we investigated AKG’s protective effects. AKG attenuated H2O2-triggered reactive oxygen species (ROS) overproduction, restored mitochondrial membrane potential, and suppressed apoptosis-related protein dysregulation. It enhanced cellular stress resistance by increasing the Bcl-2/Bax ratio, boosting antioxidant levels, and inhibiting inflammation. Mechanistically, H2O2 activated the Nrf2 pathway, while AKG amplified Nrf2 nuclear translocation and expression. Crucially, ERK inhibition abrogated AKG-mediated Nrf2 regulation, intensifying ROS accumulation and cell death. These results identify the ERK/Nrf2 axis as central to AKG’s antioxidative cytoprotection. This study advances AKG’s therapeutic potential and deepens insights into its multifunctional roles.

Fan H., Chen M., Li R., Chen Y., Zeng S., Hu W., Liu G.L., Sun C., Huang L.

Chen Y., Fan H., Li R., Zhang H., Zhou R., Liu G.L., Sun C., Huang L.

AbstractAccurate affinity assessments play an important role in drug discovery, screening, and efficacy evaluation. Label‐free affinity biosensors are recognized as a dependable and standard technology for addressing this challenge. This study constructs a free electron density gradient‐enhanced meta‐surface plasmon resonance (FED‐MSPR) biosensor through a finite‐difference time‐domain simulation model, the biosensor demonstrates superior detection performance in accurately determining affinity and kinetic rate constants. By controlling the dielectric properties of the metal on the surface of the nanocup arrays, the plasmon resonance effects are easily tuned without changing the nanostructure design. Compared with the single‐layer gold chip, the triple‐layer FED‐MSPR chip demonstrated a four‐fold improvement in resolution at the optimal resonance peak. Additionally, the sensitivity and figure of merit (FOM) of the multi‐layer chip increased by 3.5 and 7.99 times, respectively. Following modification with high‐ and low‐staggered carboxylation, the noise‐signal ratio and baseline stability of the real‐time kinetic curves based on these chips are significantly enhanced. The developed carboxylation FED‐MSPR platform is successfully used to perform affinity assays for Adalimumab and TNF‐α protein, resulting in favorable dynamic curves. These findings validate the proposed FED‐MSPR biosensor platform as cost‐effective, rapid, sensitive, and label‐free, facilitating real‐time quality control in drug development.

Gao F., Ma Z., Luo X., Wang Y., Liu X., Tang M., Chen J., Tu L., Ouyang D., Zheng J., Li C.

Chen Y., Zhang H., Li R., Fan H., Huang J., Zhou R., Yin S., Liu G.L., Huang L.

AbstractThe utilization of surface plasmon resonance (SPR) sensors for real‐time label‐free molecular interaction analysis is already being employed in the fields of in vitro diagnostics and biomedicine. However, the widespread application of SPR technology is hindered by its limited detection throughput and high cost. To address this issue, our study introduces a novel multifunctional MetaSPR high‐throughput microplate biosensor featuring 3D nanocup microarrays, aiming to achieve high‐throughput screening at a reduced cost and with enhanced speed. Different types of MetaSPR sensors and analytical detection methods have been developed for accurate subtype identification, epitope binding, affinity determination, antibody collocation, and other applications that have greatly promoted the screening and analysis of early antibody drugs. The MetaSPR platform combined with nano‐enhanced particles amplified the detection signal and improved the detection sensitivity, making it more convenient, sensitive, and efficient than traditional ELISA. Our findings demonstrated that the MetaSPR biosensor is a new practical technology detection platform that can improve the efficiency of biomolecular interaction studies with unlimited potential for new drug development.This article is protected by copyright. All rights reserved

Jean-Ruel H., Albert J.

Tilted fiber Bragg gratings (TFBGs) have been shown to possess many unique features that allow for the development of accurate sensors, especially in the biochemical realm, without excessive investments in fabrication or interrogation costs. Cross-sensitivities (including to temperature) are particularly well addressed in TFBGs, as well as simultaneous multiparameter sensing, due to their multiresonant properties. Here, after a brief review of the main characteristics of TFBGs, including interrogation and data extraction techniques, many applications will be outlined and the most recent achievements will be described through examples from the literature. This article will close with ideas for further development, in particular for better using the vast amount of data provided by TFBGs, thanks to new opportunities in machine learning and artificial intelligence.

Chen M., Fan H., Li W., Ruan J., Yang Y., Mao C., Li R., Liu G.L., Hu W.

AbstractConsidering the improved detection of biological analytes for affinity analysis is highly desirable, a metasurface plasmon resonance (Meta‐SPR)‐based imaging system, incorporating a localized SPR sensing platform with different microfluidic systems and employing simple bright‐field imaging, is established in this study. This system enables low‐level analyte concentration analysis, ranging from 100 pm to 100 nm, with the real‐time removal of nonspecific binding signals within the same device field of view. Combined with microfluidic systems and microdroplet spotting, it is possible to automatically measure the kinetic curves of a sample at ten concentration gradients or detect the specific responses of multiple samples in a single experiment simultaneously. This system can inexpensively and conveniently achieve complex detection functions, demonstrating an innovative breakthrough in sensor detection.

Bray F., Laversanne M., Sung H., Ferlay J., Siegel R.L., Soerjomataram I., Jemal A.

AbstractThis article presents global cancer statistics by world region for the year 2022 based on updated estimates from the International Agency for Research on Cancer (IARC). There were close to 20 million new cases of cancer in the year 2022 (including nonmelanoma skin cancers [NMSCs]) alongside 9.7 million deaths from cancer (including NMSC). The estimates suggest that approximately one in five men or women develop cancer in a lifetime, whereas around one in nine men and one in 12 women die from it. Lung cancer was the most frequently diagnosed cancer in 2022, responsible for almost 2.5 million new cases, or one in eight cancers worldwide (12.4% of all cancers globally), followed by cancers of the female breast (11.6%), colorectum (9.6%), prostate (7.3%), and stomach (4.9%). Lung cancer was also the leading cause of cancer death, with an estimated 1.8 million deaths (18.7%), followed by colorectal (9.3%), liver (7.8%), female breast (6.9%), and stomach (6.8%) cancers. Breast cancer and lung cancer were the most frequent cancers in women and men, respectively (both cases and deaths). Incidence rates (including NMSC) varied from four‐fold to five‐fold across world regions, from over 500 in Australia/New Zealand (507.9 per 100,000) to under 100 in Western Africa (97.1 per 100,000) among men, and from over 400 in Australia/New Zealand (410.5 per 100,000) to close to 100 in South‐Central Asia (103.3 per 100,000) among women. The authors examine the geographic variability across 20 world regions for the 10 leading cancer types, discussing recent trends, the underlying determinants, and the prospects for global cancer prevention and control. With demographics‐based predictions indicating that the number of new cases of cancer will reach 35 million by 2050, investments in prevention, including the targeting of key risk factors for cancer (including smoking, overweight and obesity, and infection), could avert millions of future cancer diagnoses and save many lives worldwide, bringing huge economic as well as societal dividends to countries over the forthcoming decades.

Cao S., Chen R., Yang Q., He X., Chiavaioli F., Ran Y., Guan B.

Pre-eclampsia is a serious multi-organ complication that severely threatens the safety of pregnant women and infants. To accurate and timely diagnose pre-eclampsia, point-of-care (POC) biosensing of the specific biomarkers is urgently required. However, one of the key biomarkers of pre-eclampsia, placental growth factor (PlGF), has a reduced level of expression in patients, which challenges the quantification capability and Limit-of-detection (LOD) of biosensors. Herein, we reported a microfiber Bragg grating biosensor for the quantification of PlGF in clinical serum samples. The Bragg grating was inscribed in a unilateral tapered fiber to generate the segmented Fabry-Perot spectrum for improving the capability of detection. Furthermore, a temperature-calibrated Bragg grating was added to enable dual parametric detection of PlGF and temperature simultaneously for removing the crosstalk. Finally, the biosensor was envisaged to be perfectly compatible with microfluidic chips, and thus dramatically reducing the sample consumption to as small as 10 μL. The proposed biosensor can respond to PlGF with concentrations ranging from 5 to 120 pg mL-1, attaining a LOD of 5 pg mL-1 of clinical relevance. More importantly, the biosensor achieved micro volume detection of clinical serum samples from patients, and the ROC curve with an AUC of 0.977 confirmed the viability of the device. Our study paves the way to a new idea for cost-effective and high-precision screening of patients with pre-eclampsia, and hence envisages a promising prospect for point-of-care (POC) diagnosis of patients with pre-eclampsia.

Zu L., Wang X., Liu P., Xie J., Zhang X., Liu W., Li Z., Zhang S., Li K., Giannetti A., Bi W., Chiavaioli F., Shi L., Guo T.

AbstractAs the population ages, the worldwide prevalence of Alzheimer's disease (AD) as the most common dementia in the elderly is increasing dramatically. However, a long‐term challenge is to achieve rapid and accurate early diagnosis of AD by detecting hallmarks such as amyloid beta (Aβ42). Here, a multi‐channel microfluidic‐based plasmonic fiber‐optic biosensing platform is established for simultaneous detection and differentiation of multiple AD biomarkers. The platform is based on a gold‐coated, highly‐tilted fiber Bragg grating (TFBG) and a custom‐developed microfluidics. TFBG excites a high‐density, narrow‐cladding‐mode spectral comb that overlaps with the broad absorption of surface plasmons for high‐precision interrogation, enabling ultrasensitive monitoring of analytes. In situ detection and in‐parallel discrimination of different forms of Aβ42 in cerebrospinal fluid (CSF) are successfully demonstrated with a detection of limit in the range of ≈30–170 pg mL−1, which is one order of magnitude below the clinical cut‐off level in AD onset, providing high detection sensitivity for early diagnosis of AD. The integration of the TFBG sensor with multi‐channel microfluidics enables simultaneous detection of multiple biomarkers using sub‐µL sample volumes, as well as combining initial binding rate and real‐time response time to differentiate between multiple biomarkers in terms of binding kinetics. With the advantages of multi‐parameter, low consumption, and highly sensitive detection, the sensor represents an urgently needed potentials for large‐scale diagnosis of diseases at early stage.

Fan H., Li R., Chen Y., Zhang H., Zeng S., Ji W., Hu W., Yin S., Li Y., Liu G.L., Huang L.

The accumulation of trace amounts of certain small molecules in food poses considerable human health challenges, including the potential for carcinogenesis and mutagenesis. Here, an ultrasensitive gold-platinum nanoflower-coupled metasurface plasmon resonance (MetaSPR) (APNMSPR) biosensor, based on a competitive immunoassay, was developed for the multiplexed and rapid quantitative analysis of trace small molecules in eggs, offering timely monitoring of food safety. This one-step biosensor can be integrated into either a newly designed detachable high-throughput MetaSPR chip-strip plate device or a standard 96-well plate for multiplexed small-molecule detection within a single egg. The limits of detection were 0.81, 1.12, and 1.74 ppt for florfenicol, fipronil, and enrofloxacin, respectively, demonstrating up to 1000-fold increased sensitivity and a 15-fold reduction in analysis time compared with those of traditional methods. The results obtained using the APNMSPR biosensor showed a strong correlation with those obtained using liquid chromatography-tandem mass spectrometry. The APNMSPR biosensor holds immense promise for the multiplexed, highly sensitive, and rapid quantitative analysis of small molecules for applications in food safety control, early diagnosis, and environmental monitoring.

You X., Liu H., Chen Y., Zhao G.

Liposomes show promise for anti-cancer drug delivery and tumor-targeted therapy. However, complex tumor microenvironments and the performance limitations of traditional liposomes restrict clinical translation. Hyaluronic acid (HA)-modified nanoliposomes effectively target CD44-overexpressing tumor cells. Combination therapy enhances treatment efficacy and delays drug resistance. Here, we developed paclitaxel (PTX) liposomes co-modified with ginsenoside compound K (CK) and HA using film dispersion. Compared to cholesterol (Ch), CK substantially improved encapsulation efficiency and stability. In vitro release studies revealed pH-responsive behavior, with slower release at pH 7.4 versus faster release at pH 5. In vitro cytotoxicity assays demonstrated that replacing Ch with CK in modified liposomes considerably decreased HCT-116 cell viability. Furthermore, flow cytometry and fluorescence microscopy showed a higher cellular uptake of PTX-CK-Lip-HA in CD44-high cells, reflected in the lower half maximal inhibitory concentrations. Overall, CK/HA-modified liposomes represent an innovative, targeted delivery system for enhanced tumor therapy via pH-triggered drug release and CD44 binding.

Wu X., Chen X., Wang X., He H., Chen J., Wu W.

Paclitaxel (PTX) is widely applied for the treatment of unresectable and metastasis breast carcinoma as well as other cancers, whereas its efficacy is always impeded by poor solubility. Liposomes are one kind of the most successful drug carriers which are capable of solubilizing PTX and improving patients’ tolerance owing to excellent biocompatibility and biodegradability. However, poor compatibility between PTX and liposomes compromises the stability, drug loading and anti-tumor capacity of liposomal formulations. To address this issue, three lipids with various chain lengths, namely, myristic acid (MA, 14C), palmitic acid (PA, 16C) and stearic acid (SA, 18C), were conjugated to PTX via ester bonds and the synthesized prodrugs with high lipophilicity were further formulated into liposomes, respectively. All liposomes show high stability and drug loadings, as well as sustained drug release. The chain lengths of lipids are negatively correlated with drug release and enzymatic conversion rates, which further impact the pharmacokinetics, tumor accumulation, and anti-tumor efficacy of liposomal PTX. Neither rapid nor slow drug release facilitates high tumor accumulation as well as anti-tumor efficacy of PTX. Among all liposomes, PTX-PA-loaded liposomes show the longest circulation and highest tumor accumulation of PTX and exert the most potent anti-tumor capacities in vivo, owing to its moderate drug release and enzymatic conversion rate. Witnessing its superior safety, PTX-PA liposomes hold potential for further clinical translation.

Zhao Y., Li R., Liu Z., Zhou H., Yang J., Zhang S., Huang L., Liu G.L., Zhang Q., Jin M.

Public health concerns have been raised by numerous reports of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and its variations infecting a range of animals. Wildlife reservoirs may facilitate the evolution of viral types capable of causing human infection in the future. Therefore, epidemiological monitoring of animals in close contact with humans is necessary. Yet, infection symptoms are not obvious in most animals, which leads to a short nucleic acid test-detection period and limits the application of this method in animals. The use of virus- and pseudovirus-based neutralizing antibody detection techniques is restricted to establishments with elevated biosafety standards. Traditional enzyme-linked immunosorbent assays (ELISA) do not offer multispecies detection and are time-consuming and labor-intensive. This work developed a polyethyleneimine-gold nanoparticle meta-surface plasmon resonance biosensor system-based multispecies SARS-CoV-2 antibody detection platform that is fast, sensitive, has a high throughput, and is fully automated. The test can be done in 30 min and specificity is up to 100% for detection in cats, dogs, and minks. Moreover, the coincidence rate was up to 99.36% (313/315) for the detection of pseudovirus in clinical and immune sera. Additionally, this method’s detection sensitivity in cat, dog, and mink serum is 2,048, 1,024, and 4,096 times, which is much better than indirect ELISA and comparable to indirect immunofluorescence assays. An efficient method for COVID-19 epidemiology screening in animal serum will be made available by this platform.

Bansal K., Devi N., Aqdas M., Kumar M., Agrewala J.N., Katare O.P., Sharma R.K., Wangoo N.

Recent years have witnessed an upsurge in the demand of new methodologies for effective anti-cancer drug delivery using green routes. In this direction, in the present work, synthesis of highly stable gold nanoparticles using aspartic acid as capping agent (GNPs) has been reported. This system was used for the efficient delivery of potent anti-cancer drug doxorubicin (Dox). To increase the cellular internalization, GNPs were loaded with cationic cell penetrating peptide, TAT via covalent or non-covalent interactions (GNPs-TAT). A high loading of TAT peptide (81.6% ± 1.84%) on GNPs was achieved successfully and was approximately double as compared to the conventional approaches (42.3% ± 1.58%). GNPs-TAT showed enhanced cellular uptake into HeLa cells in comparison to the bare GNPs which confirmed the penetrating effect of TAT peptide. Further, Dox was conjugated with GNPs-TAT via electrostatic interactions. The developed chemotherapeutic system (GNPs-TAT-Dox) showed enhanced Dox release (>80%) at acidic pH as compared to physiological pH. The cell viability results against HeLa cells indicated that the cytotoxic efficiency of the chemotherapeutic system increased twice as compared to the free Dox. Therefore, the results established a promising application of gold nanoparticles for improved drug delivery in cancer.

Cao G., Chang P., Zhang A., Liu F., Pan H., Wang J., Lin S., Yang T.

C-reactive protein (CRP) is a vital inflammatory marker in humans and a key single marker of cardiovascular diseases. In this paper, the concentration of CRP was specifically detected by a polydopamine nanospheres (PDA-NPs) developed surface plasmon resonance (SPR) sensor with high accuracy. PDA-NPs is a self-polymerizing material that can be obtained from dopamine through the mussel adhesion effect. The PDA-NPs (diameter ≈ 100 nm) modified SPR sensor exhibits enhanced refractive index (RI) sensitivity and bio-sensitivity attributed to the large specific surface area and high surface reactivity of the PDA-NPs. The developed sensor demonstrates a RI sensitivity of 2427.68 nm/RIU, presenting a 55.7% increase compared to the raw sensor (RI sensitivity was 1559.08 nm/RIU). Moreover, the developed biosensor is used to detect CRP specifically. The bio-sensitivity reaches 0.09 nm/(µg/mL), while the limit of detection (LOD) reaches 0.22 µg/mL. These findings indicate that the developed biosensor can specifically detect CRP with a low LOD. Therefore, this PDA-NPs modified biosensor has great potential in clinical detection and other bio-detection filed.