A Flexible Wearable Sensor Based on Laser-Induced Graphene for High-Precision Fine Motion Capture for Pilots.

There has been a significant shift in research focus in recent years toward laser-induced graphene (LIG), which is a high-performance material with immense potential for use in energy storage, ultrahydrophobic water applications, and electronic devices. In particular, LIG has demonstrated considerable potential in the field of high-precision human motion posture capture using flexible sensing materials. In this study, we investigated the surface morphology evolution and performance of LIG formed by varying the laser energy accumulation times. Further, to capture human motion posture, we evaluated the performance of highly accurate flexible wearable sensors based on LIG. The experimental results showed that the sensors prepared using LIG exhibited exceptional flexibility and mechanical performance when the laser energy accumulation was optimized three times. They exhibited remarkable attributes, such as high sensitivity (~41.4), a low detection limit (0.05%), a rapid time response (response time of ~150 ms; relaxation time of ~100 ms), and excellent response stability even after 2000 s at a strain of 1.0% or 8.0%. These findings unequivocally show that flexible wearable sensors based on LIG have significant potential for capturing human motion posture, wrist pulse rates, and eye blinking patterns. Moreover, the sensors can capture various physiological signals for pilots to provide real-time capturing.

Flexible Wearable Strain Sensors Based on Laser-Induced Graphene for Monitoring Human Physiological Signals.

Flexible wearable strain sensors based on laser-induced graphene (LIG) have attracted significant interest due to their simple preparation process, three-dimensional porous structure, excellent electromechanical characteristics, and remarkable mechanical robustness. In this study, we demonstrated that LIG with various defects could be prepared on the surface of polyimide (PI) film, patterned in a single step by adjusting the scanning speed while maintaining a constant laser power of 12.4 W, and subjected to two repeated scans under ambient air conditions. The results indicated that LIG produced at a scanning speed of 70 mm/s exhibited an obvious stacked honeycomb micropore structure, and the flexible strain sensor fabricated with this material demonstrated stable resistance. The sensor exhibited high sensitivity within a low strain range of 0.4-8.0%, with the gauge factor (GF) reaching 107.8. The sensor demonstrated excellent stability and repeatable response at a strain of 2% after approximately 1000 repetitions. The flexible wearable LIG-based sensor with a serpentine bending structure could be used to detect various physiological signals, including pulse, finger bending, back of the hand relaxation and gripping, blinking eyes, smiling, drinking water, and speaking. The results of this study may serve as a reference for future applications in health monitoring, medical rehabilitation, and human-computer interactions.

Plasmonic metasurface enhanced by nanobumps for label-free biosensing of lung tumor markers in serum.

Plasmonic metasurface biosensing has excellent potential in label-free detection of tumor biomarkers. In general, a variety of plasmonic metasurface nanofabrication leads to various degree of metallic surface roughness. However, the metasurface roughness effects on plasmonic sensing of tumor markers have been barely reported. Here we fabricate high-roughness (HR) gold nanohole metasurfaces with nanobumps and investigate their biosensing in comparison with the low-roughness (LR) counterparts. The HR metasurfaces demonstrate the surface sensitivity of multilayer polyelectrolyte molecules, which is 57.0% higher than the LR ones. The HR metasurfaces also illuminate higher immunoassay sensitivity to multiple lung cancer biomarkers, including carcinoembryonic antigen, neuron-specific enolase and cytokeratin fragment 21-1. The highest increasement of tumor marker sensitivity is up to 71.4%. The biosensing enhancement is attributed to the introduction of gold nanobumps on metasurfaces, which provides more hot-spot regions, higher localized near-field intensity and better optical impedance matching. Furthermore, the biosensing of HR metasurfaces effectively covers the threshold values of tumor markers for early lung cancer diagnosis, and is used for the detection of clinical serum samples. The testing deviation is less than 4% compared with commercial immunoassay, which implies promising applications on medical examinations. Our research provides a scientific guide to surface roughness engineering for plasmonic metasensing in the future point-of-care testing.

Label-free plasmonic metasensing of PSA and exosomes in serum for rapid high-sensitivity diagnosis of early prostate cancer.

Prostate-specific antigen (PSA) test is widely used to diagnose early prostate cancer (PCa). Its low sensitivity, especially in the gray zone, usually incurs overtreatment or missed diagnosis. As an emerging tumor marker, exosomes have attracted great interest in non-invasive diagnosis of PCa. However, the quick direct detection of exosomes in serum is still a big challenge for convenient screening of early PCa due to their high-degree heterogeneity and complexity. Here we develop the label-free biosensors based on wafer-scale plasmonic metasurfaces, and establish a flexible spectral methodology of exosomes profiling, which facilitates their identification and quantification in serum. We combine the metasurfaces functionalized by anti-PSA and anti-CD63, respectively, and build a portable immunoassay system to detect serum PSA and exosomes simultaneously within 20 min. Our scheme can discriminate early PCa from benign prostatic hyperplasia with a diagnostic sensitivity of 92.3%, which is much higher that of 58.3% for conventional PSA tests. The receiver operating characteristic analysis in clinical trials demonstrates significant PCa distinguishing capability with an area under the curve up to 99.4%. Our work provides a rapid and powerful approach for precise diagnosis of early PCa, and will inspire more exosomes metasensing studies for other early cancer screening.

Affinity Exploration of SARS-CoV-2 RBD Variants to mAb-Functionalized Plasmonic Metasurfaces for Label-Free Immunoassay Boosting.

Plasmonic metasurfaces (PMs) functionalized with the monoclonal antibody (mAb) are promising biophotonic sensors for biomolecular interaction analysis and convenient immunoassay of various biomarkers, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Previous PM biosensing suffers from the slow affinity detection rate and lack of sufficient immunoassay studies on various SARS-CoV-2 variants. Here, we develop a high-efficiency affinity testing method based on label-free PM sensors with mAbs and demonstrate their binding characteristics to 12 spike receptor binding domain (RBD) variants of SARS-CoV-2. In addition to the research of plasmonic near-field influence on surface biomolecule sensing, we provide a comprehensive report about the Langmuir binding equilibrium of molecular kinetics between 12 SARS-CoV-2 RBD variants and mAb-functionalized PMs, which plays a crucial role in label-free immunosensing. A high-affinity mAb can be combined with the highly sensitive propagating plasmonic mode to boost the detection of SARS-CoV-2 variants. Owing to a better understanding of molecular dynamics on PMs, we develop an ultrasensitive biosensor of the SARS-CoV-2 Omicron variant. The experiments show great distinguishment of P < 0.0001 from respiratory diseases induced by other viruses, and the limit of detection is 2 orders smaller than the commercial colloidal gold immunoassay. Our study shows the label-free biosensing by low-cost wafer-scale PMs, which will provide essential information on biomolecular interaction and facilitate high-precision point-of-care testing for emerging SARS-CoV-2 variants in the future.

Clinical Efficacy and Mechanism of Transcutaneous Neuromodulation on Functional Dyspepsia.

BACKGROUND AND AIMS: Prokinetics and proton pump inhibitors are first-line drugs for functional dyspepsia (FD) patients. However, no available treatment is effective for most FD patients, and the pathogenesis is still unclear. The purpose of this study was to investigate the therapeutic effect of transcutaneous neuromodulation (TN) on FD and its potential mechanisms. MATERIALS AND METHODS: Fifty-seven FD patients were enrolled in the study and randomly divided into 3 groups (TN Neiguan (PC6) group, TN Zusanli (ST36) group, and sham TN group) that received corresponding treatment respectively for 4 weeks. Then, all the patients enrolled received TN PC6 combined with ST36 treatment for another 4 weeks. Dyspepsia symptom questionnaire, Medical outcomes study item short form health survey (SF-36), Hospital Anxiety and Depression Scale were used to assess the severity of symptoms. Gastric accommodation, gastric emptying rate, and related parameters of electrogastrogram were used to assess the pathophysiological mechanism of FD. The possible gastrointestinal hormonal mechanism involved was assessed by detecting serum ghrelin, neuropeptide Y, and vasoactive intestinal peptide. The possible duodenal inflammation mechanism involved was assessed by detecting duodenal mucosa. RESULTS: TN treatment reduced the dyspepsia symptom score ( P <0.05) and improved the quality of life. After TN treatment, the gastric accommodation ( P <0.01), the gastric emptying rate ( P <0.01), and the percentages of preprandial ( P <0.05) and postprandial ( P <0.05) gastric slow waves (GSW) were increased. The proportions of preprandial ( P <0.05) and postprandial ( P <0.05) gastric electrical rhythm disorder were reduced. The double acupoint combination therapy further enhanced the therapeutic effect of single acupoint. In addition, the levels of ghrelin ( P <0.001) and neuropeptide Y ( P <0.001) were significantly increased, the level of vasoactive intestinal peptide ( P <0.001) was significantly decreased, and the total number of mast cells ( P <0.001) in the duodenal bulb was significantly decreased after double acupoints combination therapy. CONCLUSIONS: TN treatment significantly improves the dyspepsia symptoms of FD patients and their quality of life. TN treatment increases the percentage of normal GSW, reduces the proportion of gastric electrical rhythm disorder, and improves the gastric accommodation and gastric emptying rate. The therapeutic effect of TN may be caused by regulating gastrointestinal hormone secretion and alleviating local inflammatory responses in duodenum. In addition, the improvement of TN on GSW was closely related to the decrease of bradygastria.

Real-world evidence of biological agents in dermatology: A review of its applications, advantages, and limitations.

Randomized controlled trials (RCTs) are regarded as the gold standard of evidence-based medicine. However, the disadvantages of RCTs have been well-documented for a lengthy period of time. Due to the carefully controlled conditions, a small group of patients is studied, resulting in a lack of external validity and generalizability. To address this issue, real-world evidence (RWE) has grown in importance as a complement to randomized controlled trials (RCTs). We introduce and describe the databases used by RWE in this post. Applications of RWE are described in following aspects with examples of patients in the use of biological agents with skin diseases: (1) support the safety and efficacy outcomes of RCTs; (2) reveal real-world situations of adverse event management; (3) optimal treatment plans; (4) treatment's real-world cost burden. We also focus on its superiority of generalizability, external validity, and time and economic efficiencies as well as its deficiencies in data resources, study design, and statistical methodologies.

Exploring near-field sensing efficiency of complementary plasmonic metasurfaces for immunodetection of tumor markers.

Plasmonic metasurface biosensors have great potential on label-free high-throughput clinical detection of human tumor markers. In the past decades, nanopillar and nanohole metasurfaces have become the common choices for plasmonic biosensing, because they typically enable universal simple large-area nanopatterns via a low-cost reproducible fabrication manner. The two kinds of metasurfaces have the complementary shapes and are used to be assumed as the same type of two-dimensional plasmonic nanograting for biosensing. Up to date, there is still a lack of comparison study on their biosensing performance, which is critical to guide their better applications on tumor marker detection. In this study, we compare the bulk/surface refractive index and sensitivity of plasmonic nanopillar (PNP) and plasmonic nanohole (PNH) metasurfaces in order to evaluate their biosensing capabilities. The sensing physics about their space near-field utilization is systematically revealed. The PNH metasurface demonstrates a higher biomolecule sensitivity versus the complementary PNP metasurface, and its limit of detection for bovine serum albumin reaches ∼0.078 ng/mL, which implies a greater potential of detecting cancer biomarkers. We further adopt the PNH metasurfaces for immunoassay of three typical tumor markers by testing clinical human serum samples. The results imply that the immunodetection of alpha-fetoprotein has the most optimal sensing efficiency with the lowest detection concentration (<5 IU/mL), which is much lower than its clinical diagnosis threshold of ∼16.5 IU/mL for medical examination. Our work has not only illuminated the distinct biosensing properties of complementary metasurfaces, but also provided a promising way to boost plasmonic biosensing for point-of-care testing.

Decreased albumin-to-alkaline phosphatase ratio predicted poor survival of resectable gastric cancer patients.

BACKGROUND: The albumin-to-alkaline phosphatase ratio (AAPR) is an innovative prognostic index for various cancer patients, the clinical significance of the AAPR in patients with GC is unknown. METHODS: We retrospectively reviewed 227 resectable GC patients in our center. The Kaplan-Meier method and the Cox proportional hazards model were used to analyze the disease-free survival (DFS) and overall survival (OS). The Likelihood Ratio Test (LRT) and Akaike information criterion (AIC) were used to compare the prognostic abilities of the TNM and AAPR-TNM staging systems in DFS and OS prediction. RESULTS: The AAPR was significantly decreased in GC patients, and the optimal cut-off value for resectable and benign gastric disease was 0.437 as determined by the receiver operating characteristic (ROC) curve. The correlation analysis revealed that decreased AAPR in GC was associated with T stage (P=0.004) and TNM stage (P=0.013). Decreased preoperative AAPR correlated with both unfavorable disease-free survival (DFS) and overall survival (OS). Cox regression analysis showed that the TNM stage (DFS: P=0.001, OS: P=0.002) and differential levels of AAPR (DFS: P<0.001, OS: P<0.001) were independent risk factors of DFS and OS. ROC analysis showed that the AAPR-TNM system was more superior than the TNM staging system for DFS (z=1.91, P=0.028) and OS (z=1.937, P=0.026) prediction. The likelihood ratio test (LRT) analysis indicated that the AAPR-TNM system had a significantly larger χ2 for both DFS (35.58 vs. 34.51, P<0.001) and OS (32.92 vs. 30.07, P<0.001), and a lower Akaike information criterion (AIC) value both for DFS (1,032 vs. 1,065, P<0.001) and OS (869 vs. 898, P<0.001) compared to the TNM system. CONCLUSIONS: The AAPR level significantly decreased in patients with GC, and impacted the prognosis of patients.

Limonin ameliorates acute pancreatitis by suppressing JAK2/STAT3 signaling pathway.

Acute pancreatitis (AP) is one of the most common acute abdomen of digestive system and has the characteristics of dangerous condition and rapid development. Limonin has been confirmed to hold anti-inflammatory and antioxidant effects in various diseases. However, its potential beneficial effect on AP and the concrete mechanisms have never been revealed. Here, two mouse models were used to investigate the protective effects of limonin on AP, the caerulein-induced mild acute pancreatitis (MAP) model and L-arginine-induced severe AP (SAP) model. Firstly, it was found that limonin administration attenuated lipase and serum amylase levels and ameliorated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. Additionally, the amelioration of AP by limonin was associated with reduced levels of inflammation initiators (IL-6, IL-1ß, CCL2, and TNF-α). Mechanistically, we found that limonin suppressed the Janus Activating Kinase 2 (JAK2)/Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway, as evident by the decreased levels of JAK2 and p-STAT3. And activation of JAK2 using JAK2 activator rescued the protective effects of limonin on AP. Thus, our results demonstrate that limonin can ameliorate AP in two mice models via suppressing JAK2/STAT3 signaling pathway.

Ink stained gastric lesions: a rare cause of gastrointestinal bleeding.

A 61-year-old male was hospitalized in our department due to Intermittent melena for 4 days. Laboratory tests showed a reduced hemoglobin level (10.7 g/L). Abdominal computed tomography (CT) showed gastric wall thickening in the gastric body.

Plasmonic Metasurfaces for Medical Diagnosis Applications: A Review.

Plasmonic metasurfaces have been widely used in biosensing to improve the interaction between light and biomolecules through the effects of near-field confinement. When paired with biofunctionalization, plasmonic metasurface sensing is considered as a viable strategy for improving biomarker detection technologies. In this review, we enumerate the fundamental mechanism of plasmonic metasurfaces sensing and present their detection in human tumors and COVID-19. The advantages of rapid sampling, streamlined processes, high sensitivity, and easy accessibility are highlighted compared with traditional detection techniques. This review is looking forward to assisting scientists in advancing research and developing a new generation of multifunctional biosensors.

Combined administration of SHP2 inhibitor SHP099 and the α7nAChR agonist PNU282987 protect mice against DSS­induced colitis.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition with complex pathogenesis that currently has no cure. α7 nicotinic acetylcholine receptor (α7nAChR) is known to regulate multiple aspects of immune function. The present study aimed to evaluate the protective effects of PNU282987 and SHP099, which are a selective agonist of α7nAChR and an SHP2 inhibitor, respectively, in dextran sulfate sodium (DSS)­induced colitis in mice. Acute colitis was induced in mice using 3% DSS, and weight loss, colonic histology and cytokine production from colonic lamina propria were analyzed to evaluate disease severity. Bone marrow­derived macrophages were treated with lipopolysaccharide (LPS) to induce an inflammatory response. Cytokine expression and reactive oxygen species (ROS) levels were quantified. The α7nAChR agonist, PNU282987, and the SHP2 inhibitor, SHP099, were administered alone or in combination to LPS­induced macrophages or to colitic model mice to evaluate the inflammatory response and protective efficacy in colitis. α7nAChR protein levels were found to be markedly increased in the colon of DSS­induced colitic mice, and were found to co­localize with macrophages. Consistently, α7nAChR mRNA and protein levels were upregulated with colitis progression in DSS­induced colitic mice. Colonic inflammation was attenuated by PNU282987 treatment in DSS­induced mice, as evidenced by reduced weight loss and alleviated colonic epithelial cell disruption. These effects of PNU282987 on colitis were enhanced when it was combined with SHP099. Cytokine production and ROS levels induced by LPS in macrophages were decreased by a combination treatment of PNU282987 and SHP099. These findings identified α7nAChR as an essential element in the role of intestinal macrophages in colonic repair and demonstrated a synergistic effect of PNU282987 and SHP099, suggesting a new potential therapy for IBD.

The Value of Low-dose Prospective Dual-energy Computed Tomography with Iodine Mapping in the Diagnosis of Gastric Cancer.

OBJECTIVES: This study investigated the radiation dose and value of prospective dualenergy computed tomography (DECT) in the diagnosis of gastric cancer. METHODS: Sixty patients scheduled for computed tomography (CT) for preoperative staging were divided into two groups. Thirty patients (Group A) underwent a single contrast-enhanced abdominal CT acquisition using a dual-source mode (100 kV/140 kV). Weighted average images of the two-kilovolt acquisitions and iodine maps were created. The remaining 30 patients underwent a standard CT scan (Group B). Two observers performed a blinded read of the images for gastric lesions, evaluating the image quality and recording effective dose. RESULTS: During the blinded read, observers found 90% (27/30) of the cancers in both groups. The mean imaging quality scores were 2.1±0.9 for Group A, and 2.3±1.1 for Group B. The effective mean doses were 6.59±0.59 mSv and 25.86±0.44 mSv for Groups A and B, respectively. Compared with the control group (B), the imaging quality in the low-dose group decreased a little, but the radiation dose substantially decreased by 74.6%. CONCLUSION: The new DECT technique is valuable for examining gastric cancer patients. The dualkV scan mode can substantially reduce radiation dose while preserving good diagnostic image quality.

The early predictive role of complement C3 and C4 in patients with acute pancreatitis.

OBJECTIVE: The prognostic role of complement C3 and C4 in peripheral blood in early stage of acute pancreatitis (AP) is unknown. In this study, we aimed to evaluate the prognostic value of C3 and C4 in early stage of AP. METHODS: A total of 164 patients were enrolled in this study. The blood samples were collected within 24 hours after AP onset. We compared C3 and C4 levels in patients with different AP severity. The optimal cutoff value for them to predict severe AP (SAP) was determined by receiver operating characteristic (ROC) curve analysis. RESULTS: The reduction of C3 and C4 levels was observed. For prediction of MSAP and SAP, the AUC of C3 and C4 levels was 0.695 (95% CI: 0.612-0.779) and 0.739 (95% CI: 0.657-0.821). The cutoff value of C3 and C4 levels was 0.705 and 0.145 g/L, with the sensitivity of 0.612 and 0.735, and the specificity of 0.735 and 0.710. For prediction of SAP, the AUC of C3 and C4 levels was 0.749 (95% CI: 0.607-0.891) and 0.766 (95% CI: 0.596-0.936). The cutoff value of C3 and C4 levels was 0.400 and 0.125 g/L, with the sensitivity of 0.859 and 0.767, and the specificity of 0.600 and 0.786. CONCLUSIONS: A marked change of complement C3 and C4 was observed in peripheral blood of patients with AP, suggesting the participation of complement system in the early phase of AP. C3 and C4 levels were sensitive and accurate in judging the severity of AP.

High-throughput sequencing of circRNAs reveals novel insights into mechanisms of nigericin in pancreatic cancer.

BACKGROUND: Our previous study had proved that nigericin could reduce colorectal cancer cell proliferation in dose- and time-dependent manners by targeting Wnt/ß-catenin signaling. To better elucidate its potential anti-cancer mechanism, two pancreatic cancer (PC) cell lines were exposed to increasing concentrations of nigericin for different time periods, and the high-throughput sequencing was performed to explore the circRNA expression profiles after nigericin exposure on pancreatic cancer (PC) cells. RESULTS: In this study, a total of 183 common differentially expressed circRNAs were identified, and the reliability and validity of the sequencing data were verified by the PCR analysis. According to the parental genes of circRNAs, the GO analysis was performed to predict the most enriched terms in the biological process, cellular components and molecular functions. The KEGG analysis and pathway-pathway network exhibited the potential signal pathways and their regulatory relationships. Meanwhile, a potential competing endogenous RNA (ceRNA) mechanism through a circRNA-miRNA-mRNA network was applied to annotate potential functions of these common differentially expressed circRNAs, and these predicted miRNAs or mRNAs might be involved in nigericin damage. CONCLUSIONS: By the bioinformatics method, our data will facilitate the understanding of nigericin in PC cells, and provide new insight into the molecular mechanism of nigericin toward cancer cells. This is the first report that discusses the potential functions of nigericin in cancers through the bioinformatics method. Our data will facilitate the understanding of nigericin-mediated anti-cancer mechanisms in PC.

Hsa_circ_101555 functions as a competing endogenous RNA of miR-597-5p to promote colorectal cancer progression.

CircRNAs have been reported to exert momentous roles in regulating pathophysiological process and guiding clinical diagnosis and treatment in colorectal cancer (CRC). However, there are still a lot of circRNAs that need to be unearthed. In this study, we evaluated the expression profile of circRNAs in 10 CRC tissues and their corresponding normal-appearing tissues (NATs) by microarray, and identified that hsa_circ_101555 (circ101555) was significantly up-regulated in tumor tissues and closely related to the prognosis of CRC patients. A specific close loop structure of circ101555 was described, which was generated by back-splicing of the host gene CSNK1G1 and showed greater stability than the linear RNA. The results in vitro and in vivo showed that silencing circ101555 expression significantly suppressed cell proliferation, induced apoptosis and impaired the DNA repair capacity of CRC cells, while rescue experiments suggested that down-expression of miR-597-5p could significantly attenuate the biological effects of circ101555 knockdown on CRC cells. Subsequent experiments in vitro, including double fluorescence in situ hybridization (D-FISH) analysis, RIP analysis and biotin-coupled probe pull down assay, confirmed that miR-597-5p was effectively enriched by circ101555, and circ101555 might serve as a sponge of miR-597-5p. Moreover, two putative oncogenes (CDK6 and RPA3) were identified as the miR-597-5p potential targets. Taken together, our results proved that circ101555 might function as a competing endogenous RNA of miR-597-5p to up-regulate CDK6 and RPA3 expression in CRC. Circ101555 could be a useful prognostic indicator in patients with CRC, and silence of circ101555 provided a new attractive therapeutic measure for CRC.