Intelligent tunable CAR-T cell therapy leads the new trend.

Adoptive transfer of T cells engineered with chimeric antigen receptor (CAR) has been proved to have robust anti-tumor effects against hematological malignancies. However, problems about safety and efficacy, such as cytokine release syndrome (CRS), T cell exhaustion and antigen escape are still raised when patients are treated with CAR-T cells. Moreover, CAR-T therapy has limited applications in treating solid tumors, owing to inefficient infiltration and poor functional persistence of CAR-T cells and diverse immunosuppression in tumor microenvironment. In order to overcome these limitations and broad its applications, multiple controllable CAR-T technologies were exploited. In this article, we review the designs of intelligent controlled CAR-T technologies and the innovations that they bring about in recent years.

A Multiphase Coupled Hydrodynamic Model for Fate and Transport Simulation of Polycyclic Aromatic Hydrocarbons in a Semi-Closed Narrow Bay.

With their unique geographical characteristics, semi-closed narrow bays are important places for human survival but vulnerable to pollution. Because pollutants (polycyclic aromatic hydrocarbons, PAHs) migrate and undergo transformation through a dynamic mechanism in bays of this type, environmental authorities have formulated a series of effective measures for pollution prevention and control, but these are difficult to realize. Based on monitoring and historical data, a multiphase-coupled hydrodynamic model combined with a carcinogenic risk-assessment model was able to solve the challenging environmental problem. Results showed that the hydrodynamic condition in the semi-closed narrow bay was very complex. A weaker hydrodynamic force had an adverse influence on the diffusion of pollutants, further amplified in part by the head of the semi-closed narrow bay, resulting in a higher ecological risk. The prediction results indicated that the total amount of PAHs transported from seawater to sediments was about 4.7 × 1013 ng/year, which might cause serious threats to aquaculture or human health.

Distribution and characteristics of microplastics in sediment at representative dredged material ocean dumping sites, China.

Dredged material ocean dumping activities are likely an important source of microplastics (MPs) in coastal areas but have received little attention globally. In this study, we investigated the spatiotemporal distribution and characteristics of MPs in sediments at eight dredged material dumping sites of China. MPs were separated from sediment through density flotation, and polymer types were identified using µ-FTIR. The results showed that the average MP abundance was 112.82 ± 109.68 items/kg d.w. The MPs were more abundant at nearshore dumping sites than at distant dumping sites. Dumping activities may be the main contributor of MPs to Site BD1, the farthest dumping site from shore, but only a minor source of MPs at the other dumping sites. The characteristics of MPs were dominated by transparent PET fibers <1 mm. Overall, sediments at the dumping sites exhibited relatively low to moderate concentrations of MPs in comparison to most other coastal sediments.

Mitophagy alleviates cisplatin-induced renal tubular epithelial cell ferroptosis through ROS/HO-1/GPX4 axis.

Cisplatin is widely recommended in combination for the treatment of tumors, thus inevitably increasing the incidence of cisplatin-induced acute kidney injury. Mitophagy is a type of mitochondrial quality control mechanism that degrades damaged mitochondria and maintains cellular homeostasis. Ferroptosis, a new modality of programmed cell death, is characterized by iron-dependent phospholipid peroxidation and oxidative membrane damage. However, the role of mitophagy in ferroptosis in kidney disease is unclear. Here, we investigated the mechanism underlying both BNIP3-mediated and PINK1-PARK2-mediated mitophagy-induced attenuation of ferroptosis in cisplatin-induced acute kidney injury. The results showed that cisplatin induced mitochondrial injury, ROS release, intracellular iron accumulation, lipid peroxidation and ferroptosis in the kidney, which were aggravated in Bnip3 knockout, Pink1 knockout or Park2 knockout cisplatin-treated mice. Ferrstatin-1, a synthetic antioxidative ferroptosis inhibitor, rescued iron accumulation, lipid peroxidation and ferroptosis caused by inhibition of mitophagy. Thus, the present study elucidated a novel mechanism by which both BNIP3-mediated and PINK1-PARK2-mediated mitophagy protects against cisplatin-induced renal tubular epithelial cell ferroptosis through the ROS/HO1/GPX4 axis.

CRISPR Cas12a-Powered Silicon Surface-Enhanced Raman Spectroscopy Ratiometric Chip for Sensitive and Reliable Quantification.

Sensitive and reliable clustered regularly interspaced short palindromic repeats (CRISPR) quantification without preamplification of the sample remains a challenge. Herein, we report a CRISPR Cas12a-powered silicon surface-enhanced Raman spectroscopy (SERS) ratiometric chip for sensitive and reliable quantification. As a proof-of-concept application, we select the platelet-derived growth factor-BB (PDGF-BB) as the target. We first develop a microfluidic synthetic strategy to prepare homogeneous silicon SERS substrates, in which uniform silver nanoparticles (AgNPs) are in situ grown on a silicon wafer (AgNPs@Si) by microfluidic galvanic deposition reactions. Next, one 5'-SH-3'-ROX-labeled single-stranded DNA (ssDNA) is modified on AgNPs via Ag-S bonds. In our design, such ssDNA has two fragments: one fragment hybridizes to its complementary DNA (5'-Cy3-labeled ssDNA) to form double-stranded DNA (dsDNA) and the other fragment labeled with 6'-carboxy-X-rhodmine (ROX) extends out as a substrate for Cas12a. The cleavage of the ROX-tagged fragment by Cas12a is controlled by the presence or not of PDGF-BB. Meanwhile, Cy3 molecules serving as internal standard molecules still stay at the end of the rigid dsDNA, and their signals remain constant. Thereby, the ratio of ROX signal intensity to Cy3 intensity can be employed for the reliable quantification of PDGF-BB concentration. The developed chip features an ultrahigh sensitivity (e.g., the limit of detection is as low as 3.2 pM, approximately 50 times more sensitive than the fluorescence counterpart) and good reproducibility (e.g., the relative standard deviation is less than 5%) in the detection of PDGF-BB.

Longitudinal associations of serum survivin with the severity and prognosis of community-acquired pneumonia patients.

BACKGROUND: Survivin is a member of apoptosis inhibitor proteins that evokes cellular proliferation and inhibits apoptosis. However, the role of survivin in community-acquired pneumonia (CAP) patients remains to be firmly established. The aim of this cohort study was to evaluate the correlations of serum survivin with the severity and prognosis of CAP patients. METHODS: This research included 470 eligible CAP patients. Serum fasting samples were drawn from patients, and serum survivin was measured by enzyme-linked immunosorbent assay (ELISA). Meanwhile, demographic characteristics and clinical information were collected. The prognosis of CAP patients was tracked. RESULTS: Serum survivin gradually decreased with elevated CAP severity scores. Additionally, the correlative analysis suggested that serum survivin was associated with many clinical characteristics. Furthermore, mixed linear and logistic regression models indicated that serum survivin was negatively associated with severity. After adjusting for confounding factors, logistic regression analyses found that lower serum survivin on admission elevated the risks of mechanical ventilation, vasoactive agent usage, longer hospital stays, ICU admission, and even death during hospitalization. Serum survivin in combination with CAP severity scores elevated the predictive capacities for severity and death in CAP patients compared with a single indicator. CONCLUSION: On admission, there are inverse dose-response associations of serum survivin with severity and poor prognosis in CAP patients, demonstrating that serum survivin may be involved in the pathophysiology process of CAP. Serum survivin may serve as a potential biomarker for disease evaluation and prognosis in CAP patients.

Serum TRAIL predicts severity and prognosis in patients with community-acquired pneumonia: a prospective cohort study.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) can trigger the apoptosis pathways through binding to relative death receptors. However, the relationship of TRAIL with community-acquired pneumonia (CAP) was unclear. This study aims at exploring the relationships between circulatory TRAIL with severity and prognosis in CAP patients through a prospective cohort study. The whole of 239 CAP patients was enrolled. Demographic characteristics and clinical information were analyzed. TRAIL and inflammatory cytokines were measured using enzyme-linked immunosorbent assay (ELISA). Circulatory TRAIL was gradually increased in accord with CAP severity scores. Spearman or Pearson correlative analysis indicated that circulatory TRAIL was strongly associated with physiologic indicators among CAP patients. Mixed logistic and linear regression models revealed that circulatory TRAIL was positively correlated with the severity scores in CAP patients. After adjusting for confounders, higher levels of circulatory TRAIL on admission significantly elevated the risks of ICU admission, mechanical ventilation, longer hospital stays, or even death during hospitalization. The predictive capacities of serum TRAIL for death were higher compared with CAP severity scores, inflammatory and infectious indicators. There are obviously positive dose-response relationships between circulatory TRAIL on admission with the severity and poor prognostic outcomes in CAP patients. Circulatory TRAIL on admission may be used as a potential biomarker in predicting the severity and poor prognosis for CAP patients.

Rethinking the Selection of Pathological T-Classification for Non-Small-Cell Lung Cancer in Varying Degrees of Visceral Pleural Invasion: A SEER-Based Study.

Background: The T classification of non-small-cell lung cancer (NSCLC) was upgraded from T1 to T2 when accompanied by visceral pleural invasion (VPI). However, the association between VPI and prognostic outcomes was obscure in NSCLC patients with ≤3 cm tumor size (TS), which leaded the controversy of selection of T classification. The goal was to evaluate the effect of VPI on the prognosis of NSCLC with ≤ 3cm TS and present a modified T classification. Methods: A total of 14,934 NSCLC patients without distant metastasis were recruited through a retrospective study in the SEER database. The effect of VPI on lung cancer specific survival (LCSS) was evaluated using survival curve and COX regression analysis in NSCLC patients with ≤3 cm TS. Results: Although there was no difference of the LCSS of PL0 and PL1 patients with ≤2 cm TS in patients without lymph node (LN) metastasis, the LCSS was lower in PL2 patients than those in PL0 (T1a: p < 0.001; T1b: p = 0.001). Moreover, the LCSS was decreased in PL1 and PL2 patients with 2-3 cm TS compared with PL0 (T1c: PL1, p < 0.001; PL2, p = 0.009) of patients without LN metastasis. No difference of LCSS was observed in patients with LN metastasis between PL0 with PL1 and PL2. Conclusion: In NSCLC patients without LN metastasis and TS ≤ 2 cm, tumor with PL1 should remain defined as T1, tumor with PL2 should be defined as T2. However, 2-3 cm TS patients with PL1 or PL2 should both defined as T2. Meanwhile, ≤3 cm TS patients with LN metastasis can be regarded as T1, whether NSCLC patients accompanied with PL1 or PL2.

Cross-sectional and longitudinal associations of serum Cysteine-rich 61 with severity and prognosis among community-acquired pneumonia patients in China.

Background: Cysteine-rich 61 (CYR61) is implicated in many pulmonary diseases. However, the relationship between CYR61 and community-acquired pneumonia (CAP) patients was unknown. This research aimed to estimate the correlations of serum CYR61 with severity and prognosis in CAP patients through a prospective cohort study. Methods: All 541 CAP patients were enrolled in this study. Fasting venous blood was collected. Clinical characteristics and demographic information were obtained. CYR61 and inflammatory cytokines were detected in serum using ELISA. Results: Serum CYR61 was gradually increased in parallel with severity scores in CAP patients. Correlative analysis indicated that serum CYR61 was strongly associated with many clinical parameters in CAP patients. Moreover, mixed logistic and linear regression models found that there were positive correlations between serum CYR61 and CAP severity scores after adjusted for age, BMI, and respiratory rate. Stratified analyses suggested that age affected the associations between serum CYR61 and severity scores. On admission, higher serum CYR61 levels elevated the risks of mechanical ventilation, vasoactive agent, ICU admission, death, and longer hospital stays during hospitalization. Moreover, serum CYR61 in combination with severity scores upregulated the predictive capacities for severity and death than single serum CYR61 or severity scores in CAP patients. Conclusion: There are significantly positive dose-response associations of serum CYR61 on admission with the severity and adverse prognostic outcomes, demonstrating that CYR61 is involved in the pathophysiology of CAP. Serum CYR61 may be used as a potential biomarker for the diagnosis and prognosis in CAP patients.

Serum Level of 4-Hydroxynonenal in Community-Acquired Pneumonia: A Potential Biomarker for Severity and Prognosis.

Background: Four-hydroxynonenal (4-HNE) exerts a central role in the pathophysiological process of pulmonary diseases. The aim of this project was to evaluate the correlations between serum 4-HNE with severity and prognosis in patients with community-acquired pneumonia (CAP) by a prospective cohort study. Materials and Methods: A total of 239 patients with CAP and healthy volunteers were recruited. Fasting blood was collected. Serum 4-HNE was measured with ELISA. Clinical characteristics and demographic information were obtained. The relationships between serum 4-HNE and clinical characteristics were evaluated through the Spearman or Pearson correlation coefficient. The associations of serum 4-HNE with severity and prognosis were estimated through logistic regression analysis. Results: On admission, serum 4-HNE was upregulated in patients with CAP compared with healthy volunteers. Serum 4-HNE was gradually increased in line with CAP scores. Additionally, elderly patients with CAP were more prone to suffer from 4-HNE elevation. Moreover, serum 4-HNE was positively correlated with CAP severity scores. Meanwhile, the poor prognostic outcomes were tracked among patients with CAP. Higher serum 4-HNE on admission increased the risks of mechanical ventilation, vasoactive agent usage, and death in patients with CAP during hospitalization. The predictive powers for severity and death were increased in serum 4-HNE compared with CAP severity scores and inflammatory cytokines. Conclusion: Serum 4-HNE on admission is positively correlated with the severity and poor prognosis among patients with CAP, indicating that 4-HNE participates in the pathophysiology of CAP. Serum 4-HNE may be used as an earlier biomarker for diagnosis and prognosis in patients with CAP.

Captive Rearing of Longfin Smelt Spirinchus thaleichthys: First Attempt of Weaning Cultured Juveniles to Dry Feed.

The rapid decline of longfin smelt Spirinchus thaleichthys, a threatened euryhaline forage fish in California, is a serious concern for scientists and resource managers. To recover and conserve this species, a captive culture program was initiated, focusing on the collection, captive rearing and breeding of wild broodstock, and the rearing of their offspring. Although progress has been made in the collection of broodstock and the production and culturing of larvae, no studies have evaluated the rearing of juvenile life stages in captivity. The present study examines methodological considerations for culturing F1 juvenile longfin smelt, specifically, the first efforts toward weaning juveniles to a dry commercial pellet feed. Cultured juvenile longfin smelt were fed live Artemia only or co-fed Artemia and dry feed for 62 days, and the effects of feed type on juvenile survival, growth, body condition, and fatty acid profiles were examined. No significant differences were observed between feeding treatments, despite an 80% reduction in Artemia in the co-feeding treatment. Furthermore, examination of fish stomach contents at the end of the trial confirmed the transition to dry feed. This is the first study to indicate successful feeding by longfin smelt on dry commercial pellets, and suggests that juvenile longfin smelt can be fully weaned onto dry feeds. Results of this study are critical for closing the lifecycle of longfin smelt in captivity and developing a successful conservation culture program for this imperiled species.

In Situ Monitoring of Dynamic Photocatalysis of Metal-Organic Frameworks by Three-Dimensional Shell-Isolated Nanoparticle-Enhanced Raman Spectroscopy.

Metal-organic frameworks (MOFs) are promising as novel disinfectants due to the reactive oxygen species (ROS) produced in their photocatalytic processes. The optimal MOF is screened as the best disinfectant, representing high-efficacy production of ROS under photocatalytic conditions. However, current methods to screen abundant MOFs for disinfectant application are generally semiquantitative or ex situ methods [such as electron paramagnetic resonance (EPR) measurements], so achieving a strategy that can quantitatively screen an optimal MOF in situ and is reliable is demanded. Herein, we developed a three-dimensional (3D) shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) platform to study the dynamic photocatalytic processes of various MOFs (e.g., ZIF-67, ZIF-8, and UIO-66) in situ. This platform comprises silica shell-isolated gold nanoparticles (AuNPs) modified on silicon nanowire arrays (SiNWArs). The MOF is then self-assembled on the 3D-SHINERS substrate. Using this platform, we recorded dynamic spectroscopic evidence of ROS formation by various MOFs under sunlight irradiation. By dynamic comparison, ZIF-67 has the most robust photocatalytic efficiency, ∼1.7-fold stronger than that of ZIF-8 and ∼42.6-fold stronger than that of UIO-66. As expected, ZIF-67 displays the best antibacterial ability, up to 99% in the agar plate assay. This work provides a versatile platform for dynamically monitoring photocatalytic performance and screening antibacterial MOFs.

Bacteria eat nanoprobes for aggregation-enhanced imaging and killing diverse microorganisms.

Currently optical-based techniques for in vivo microbial population imaging are limited by low imaging depth and highly light-scattering tissue; and moreover, are generally effective against only one specific group of bacteria. Here, we introduce an imaging and therapy strategy, in which different bacteria actively eat the glucose polymer (GP)-modified gold nanoparticles through ATP-binding cassette (ABC) transporter pathway, followed by laser irradiation-mediated aggregation in the bacterial cells. As a result, the aggregates display ~15.2-fold enhancement in photoacoustic signals and ~3.0-fold enhancement in antibacterial rate compared with non-aggregated counterparts. Significantly, the developed strategy allows ultrasensitive imaging of bacteria in vivo as low ~105 colony-forming unit (CFU), which is around two orders of magnitude lower than most optical contrast agents. We further demonstrate the developed strategy enables the detection of ~107 CFU bacteria residing within tumour or gut. This technique enables visualization and treatment of diverse bacteria, setting the crucial step forward the study of microbial ecosystem.

Autophagy-dependent ferroptosis in kidney disease.

Ferroptosis is a new type of cell death caused by the lack of glutathione peroxidase 4 (GPX4) and the imbalance of cellular redox. It is characterized by the accumulation of lipid peroxides on cell membranes. Multiple regulatory pathways of ferroptosis include the GPX4, glutamate-cystine antiporter (System Xc-), lipid metabolism, and iron metabolism pathways. Recent studies have reported that autophagy-dependent ferroptosis (ferroptosis meditated by ferritinophagy, lipophagy, and clockophagy) plays a significant role in the occurrence of several diseases, including diseases affecting the nerves, liver, lungs, and kidneys. This review provides an overview of research progress made on autophagy-dependent ferroptosis in kidney diseases.

Serum 8-Hydroxydeoxyguanosine Is a Potential Indicator for the Severity and Prognosis in Patients with Community-Acquired Pneumonia: A Prospective Cohort Study.

Previous studies have demonstrated that 8-hydroxydeoxyguanosine (8-OHdG) exerted key roles in various pulmonary diseases, but the evidence for its role in community-acquired pneumonia (CAP) was lacking. The goal of this research was to evaluate the correlations of serum 8-OHdG with the severity and prognosis among patients with CAP through a prospective cohort study. A total of 239 patients with CAP and 239 healthy participants were enrolled. Fasting blood samples were collected. 8-OHdG and inflammatory cytokines were measured by ELISA. On admission, serum 8-OHdG was significantly increased in patients with CAP compared with control subjects. Besides, serum 8-OHdG was incrementally increased in line with CAP severity scores. Pearson correlative analysis found that serum 8-OHdG was correlated with clinical characteristics and inflammatory cytokines in patients with CAP. Linear and logistic regression analysis showed that serum 8-OHdG was positively associated with CAP severity scores. Furthermore, the prognostic outcomes were tracked. Higher serum 8-OHdG on admission increased the risks for intensive care unit admission, mechanical ventilation, vasoactive agent usage, death, and longer hospital stay among patients with CAP. Serum 8-OHdG combination with confusion, respiratory rate, blood pressure, and age ≥65 y or pneumonia severity index had stronger predictive powers for death than single 8-OHdG, CAP severity scores, or several inflammatory cytokines in patients with CAP. These results indicated that serum 8-OHdG is positively associated with the severity and poor prognosis in patients with CAP, demonstrating that 8-OHdG may be involved in the pathophysiology process of CAP.

Serum cadmium positively correlates with inflammatory cytokines in patients with chronic obstructive pulmonary disease.

BACKGROUND: Cadmium is a ubiquitous toxic heavy metal and environmental toxicant. Inflammation exerts central roles in the process of chronic obstructive pulmonary disease (COPD). However, few epidemiological studies on the correlation between cadmium exposure and COPD are available. The aim of this study was to evaluate the correlations among serum cadmium, inflammatory cytokines and pulmonary function in COPD patients. METHODS: All 940 COPD patients were finally recruited in this study. Demographic characteristics and clinical information were extracted. Fasting serum was collected. Serum cadmium was detected through graphite furnace atomic absorption spectrophotometry. Serum inflammatory cytokines were measured using enzyme-linked immunosorbent assay. RESULTS: All patients were classified into three groups according to the tertile division of serum cadmium concentration: low (<0.77 µg/L, L), medium (0.77-1.01 µg/L, M), and high (1.01 µg/L, H). Logistic regression analysis found that serum cadmium was inversely correlated with pulmonary function before and after adjusted confounding variables. When stratified by gender, serum cadmium was still negatively correlated with pulmonary function in COPD patients. Moreover, higher serum cadmium elevated CAT (COPD Assessment Test) score before and after adjusted confounding variables. Though a non-linear association between serum cadmium and inflammatory cytokines, serum cadmium was positively associated with inflammatory cytokines (TNF-α and MCP-1). TNF-α and MCP-1 exerted a partial mediator in the association between cadmium exposure and pulmonary function decline in COPD patients. CONCLUSIONS: Serum cadmium concentration is inversely correlated with pulmonary function among COPD patients. Inflammatory cytokines may be important mediators for cadmium-induced pulmonary function decline in COPD patients.

Serum interleukin-17 predicts severity and prognosis in patients with community acquired pneumonia: a prospective cohort study.

BACKGROUND: Some studies previously demonstrated that interleukin-17 (IL-17) involves in pulmonary diseases progression. Nevertheless, the role of IL-17 in community-acquired pneumonia (CAP) remains unknown. This study aims to examine the correlations between serum IL-17 with the severity and prognosis in CAP patients through a prospective cohort study. METHODS: All 239 CAP patients were recruited. Serum IL-17 was detected by enzyme-linked immunosorbent assay (ELISA). The CAP severity was evaluated through CAP severity scores, including CURB-65, CRB-65, PSI, SMART-COP, CURXO and APACHE II. RESULTS: Serum IL-17 was gradually increased consistent with the severity of CAP. Correlative analysis suggested that serum IL-17 was associated with clinical physiologic indicators among CAP patients. Logistic regression indicated that serum IL-17 was positively related to CAP severity scores. Additionally, the prognostic outcomes were tracked among CAP patients. The levels of IL-17 on admission were significantly increased in CAP patients with ICU admission, mechanical ventilation, vasoactive agent, death and longer hospitalization days. Logistic regression analyses revealed serum higher IL-17 on admission elevated the risks of vasoactive agent usage and longer hospital stays in CAP patients. The cut-off concentrations of serum IL-17 for death, ICU admission, mechanical ventilation and ≥ 14 hospital stays were 86.80 ng/mL, 84.92 ng/mL, 84.92 ng/mL and 60.29 ng/mL respectively. CONCLUSIONS: Serum IL-17 on admission is positively associated with the severity and poor prognosis among CAP patients, revealing that IL-17 may implicate in the pathological process of CAP. Therefore, serum IL-17 may become an effective biomarker for diagnosis, prognosis and therapy for CAP patients.

Associations of Serum Resistin With the Severity and Prognosis in Patients With Community-Acquired Pneumonia.

Background: Resistin is an endogenous ligand of Toll-like receptor 4 that activates several inflammatory signals. But the physiological function of resistin in community-acquired pneumonia (CAP) remains unknown. The goal of this research was to explore the associations between serum resistin and the severity and prognosis in CAP patients through a retrospective cohort study. Methods: All 212 CAP patients and 106 healthy cases were enrolled. Demographic characteristics were extracted. Serum resistin was determined via enzyme-linked immunosorbent assay. The prognosis was tracked in CAP patients. Results: Serum resistin on admission was raised in CAP patients compared with control cases. The level of resistin was gradually increased in parallel with CAP severity scores in CAP patients. Pearson and Spearman analyses revealed that serum resistin was positively correlated with CAP severity scores, white blood cells, urea nitrogen, creatinine, and inflammatory cytokines among CAP patients. There were negative relationships between resistin and hematocrit and albumin in CAP patients. Besides, linear and logistic regression analyses further indicated that serum resistin on admission was positively associated with CAP severity scores among CAP patients. Follow-up research revealed that serum resistin elevation on admission prolonged hospital stay in CAP patients. Conclusion: Serum resistin on admission is positively correlated with the severity and hospital stay in CAP patients, indicating that resistin may be involved in the physiological process of CAP. Serum resistin may be a potential biomarker in the diagnosis and prognosis for CAP.

Investigation of photoacoustic tomography reconstruction with a limited view from linear array.

SIGNIFICANCE: As linear array transducers are widely used in clinical ultrasound imaging, photoacoustic tomography (PAT) with linear arrays is similarly suitable for clinical applications. However, due to the limited-view problem, a linear array has limited performance and leads to artifacts and blurring, which has hindered its broader application. There is a need to address the limited-view problem in PAT imaging with linear arrays. AIM: We investigate potential approaches for improving PAT reconstruction from linear array, by optimizing the detection geometry and implementing iterative reconstruction. APPROACH: PAT imaging with a single-array, dual-probe configurations in parallel-shape and L-shape, and square-shape configuration are compared in simulations and phantom experiments. An iterative model-based algorithm based on the variance-reduced stochastic gradient descent (VR-SGD) method is implemented. The optimum configuration found in simulation is validated on phantom experiments. RESULTS: PAT imaging with dual-probe detection and VR-SGD algorithm is found to improve the limited-view problem compared to a single probe and provide comparable performance as full-view geometry in simulation. This configuration is validated in experiments where more complete structure is obtained with reduced artifacts compared with a single array. CONCLUSIONS: PAT with dual-probe detection and iterative reconstruction is a promising solution to the limited-view problem of linear arrays.

Surface-enhanced Raman scattering holography chip for rapid, sensitive and multiplexed detection of human breast cancer-associated MicroRNAs in clinical samples.

MicroRNAs (miRNAs) are promising biomarkers for the early diagnosis of breast cancer. Yet, simultaneous achievement of rapid, sensitive and accurate detection of diverse miRNAs in clinical samples is still challenging due to the low abundance of miRNAs and the complex procedures of RNA extraction and separation. Herein, we develop an innovative three-dimensional (3D) surface-enhanced Raman scattering (SERS) holography sensing strategy for rapid, sensitive and multiplexed detection of human breast cancer-associated miRNAs. To establish a proof of concept, nine kinds of human breast cancer-associated miRNAs are isothermally amplified by Exonuclease (Exo) III enzyme, and the products could be spatially separated to corresponding sensing region on silicon SERS substrates. Each region has been modified with corresponding hairpin DNA probes, which are used to identify and quantify the miRNAs. Different DNA probes are labeled with different Raman reporters, which serve as "SERS tags" to incorporate spectroscopic information into computer-generated 3D SERS hologram within ~9 min. We demonstrate that 3D SERS holography chip not only achieves an ultrahigh sensitivity down to ~1 aM but also feature a high correlation with RT-qPCR in the detection of nine miRNAs in 30 clinical serum samples. This work provides a feasible tool to improve the diagnosis of breast cancer.