High-contrast handheld FFOCT system for tissue imaging.

A low contrast is a limiting factor for imaging a microstructure beneath the biological sample surface. In this work, we describe a novel, to our knowledge, full-field optical coherence tomography (FFOCT) system with a probe connected by a fiber bundle and a multimode optical fiber. The device is based on the tandem structure of the Michelson interferometer and the Fizeau interferometer. One advantage of our device is that light propagates through the fiber bundle only once, greatly improving detection sensitivity. In addition, by spatial filtering in the Fourier domain and inverse filtering, the effects of pixelation artifacts and multiple scattering in the en face images obtained by our system are suppressed. The depth-resolved en face images of the human finger skin ex vivo and the porcine esophagus ex vivo are presented to demonstrate the capability of our system.

The significance and prognostic value of multifocal papillary thyroid carcinoma in children and adolescents.

INTRODUCTION: The prognostic value of multifocality in paediatric papillary thyroid carcinoma (PTC) patients remains a subject of debate. This study aimed to explore the clinical significance and prognostic value of multifocality in children and adolescents with PTC. METHODS: This study retrospectively analysed the clinicopathological characteristics and postoperative follow-up data of 338 PTC patients aged ≤ 20 years from May 2012 to July 2022. The clinical and pathological characteristics of 205 patients with unifocal lesions and 133 patients with multifocal lesions were compared. A logistic regression model evaluated the relationship between multifocal lesions and disease recurrence/persistence in children and adolescents with PTC. Based on the median follow-up time of children with multifocal PTC, 114 patients with multifocal PTC older than 20 years were added, and the clinicopathological characteristics were compared between the 133. paediatric/adolescent patients and 114 adult patients with multifocal PTC. RESULTS: Among the paediatric and adolescent patients, over a median follow-up time of 49 months, 133 had multifocal disease and 205 had unifocal disease. Multifocal PTC patients exhibited stronger invasiveness in the form of extrathyroidal extension, tumour diameter, lymph node metastasis, and distant metastasis. Multifocality (OR 2.68; p = 0.017), lateral lymph node metastasis (OR 2.85; p = 0.036), and distant metastasis (OR 4.28; p = 0.010) were identified as independent predictive factors for the recurrence/persistence of disease. Comparing the paediatric/adolescent vs. adult multifocal patients, the former demonstrated greater tumour invasiveness. Lateral lymph node metastasis (OR 6.36; P = 0.012) and distant metastasis (OR 3.70; P = 0.027) were independent predictive factors for recurrence/persistence of disease in multifocal patients, while age was not (OR 0.95; P = 0.455). CONCLUSION: Tumour multifocality independently predicts persistent/recurrent disease in paediatric and adolescent PTC patients.

Clinical Value of Bioresorbable Scaffolds in Patients with Non-left Main Bifurcation Lesions Undergoing Percutaneous Coronary Intervention.

Aim: To compare the operation-related indexes, complication rates, and cardiac function indexes of bioresorbable scaffolds with drug-eluting scaffolds in coronary non-left main stem lesions and to clarify the clinical value of bioresorbable scaffolds in percutaneous coronary intervention for non-left main stem lesions. Methods: The retrospective study sample consisted of 60 non-left main stem lesions treated using bioresorbable stent or drug-eluting stents between June 2022 and June 2023. Comparison of surgical operation-related indexes, intraoperative and postoperative complications, cardiac function indexes, adverse cardiovascular events, and surgical success rate between the two groups. Results: The surgical operation time and X-ray exposure time of the experimental group were shorter than those of the control group, and contrast agent dosage was lower than that of the control group (P < .05). Left ventricular ejection fraction (LVEF) was higher than that in the control group at one month after surgery, and left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) in the experimental group was lower than that in the control group, and the difference was statistically significant (P < .05). The total incidence of major adverse cardiovascular events was lower in the experimental group than in the control group (15.6% VS. 71.4%)(P < .05). Conclusion: Bioresorbable scaffolds are more effective than drug-eluting scaffolds in treating non-left main stem lesions by percutaneous coronary intervention. Furthermore, bioresorbable scaffolds could be considered a preferable option for certain patients undergoing percutaneous coronary intervention for non-left main stem lesions.

Antibody responses to SARS-CoV-2 Omicron infection in patients with hematological malignancies: A multicenter, prospective cohort study.

Little is known about antibody responses to natural Omicron infection and the risk factors for poor responders in patients with hematological malignancies (HM). We conducted a multicenter, prospective cohort study during the latest Omicron wave in Chongqing, China, aiming to compare the antibody responses, as assessed by IgG levels of anti-receptor binding domain of spike protein (anti-S-RBD), to Omicron infection in the HM cohort (HMC) with healthy control cohort (HCC), and solid cancer cohort (SCC). In addition, we intend to explore the risk factors for poor responders in the HMC. Among the 466 HM patients in this cohort, the seroconversion rate was 92.7%, no statistically difference compared with HCC (98.2%, p = 0.0513) or SCC (100%, p = 0.1363). The median anti-S-RBD IgG titer was 29.9 ng/mL, significantly lower than that of HCC (46.9 ng/mL, p < 0.0001) or SCC (46.2 ng/mL, p < 0.0001). Risk factors associated with nonseroconversion included no COVID-19 vaccination history (odds ratio [OR] = 4.58, 95% confidence interval [CI]: 1.75-12.00, p = 0.002), clinical course of COVID-19 ≤ 7 days (OR = 2.86, 95% CI: 1.31-6.25, p = 0.008) and severe B-cell reduction (0-10/µL) (OR = 3.22, 95% CI: 1.32-7.88, p = 0.010). Risk factors associated with low anti-S-RBD IgG titer were clinical course of COVID-19 ≤ 7 days (OR = 2.58, 95% CI: 1.59-4.18, p < 0.001) and severe B-cell reduction (0-10/µL) (OR = 2.87, 95% CI: 1.57-5.24, p < 0.001). This study reveals a poor antibody responses to Omicron (BA.5.2.48) infection in HM patients and identified risk factors for poor responders. Highlights that HM patients, especially those with these risk factors, may be susceptible to SARS-CoV-2 reinfection, and the postinfection vaccination strategies for these patients should be tailored. Clinical trial: ChiCTR2300071830.

A novel pharmacological mechanism of anti-cancer drugs that induce pyroptosis.

Pyroptosis is an inflammasome-induced lytic form of programmed cell death, and its main effect involves the release of inflammatory mediators when a cell dies, resulting in an inflammatory response in the body. The key to pyroptosis is the cleavage of GSDMD or other gasdermin families. Some drugs can cause cleavage GSDMD or other gasdermin members cause pyroptosis and suppress cancer growth and development. This review explores several drugs that may induce pyroptosis, thereby contributing to tumor treatment. Pyroptosis-inducing drugs, such as arsenic, platinum, and doxorubicin, were used originally in cancer treatment. Other pyroptosis-inducing drugs, such as metformin, dihydroartemisinin, and famotidine, were used to control blood glucose, treat malaria, and regulate blood lipid levels and are effective tumor treatments. By summarizing drug mechanisms, we provide a valuable basis for treating cancers by inducing pyroptosis. In future, the use of these drugs may contribute to new clinical treatments.

Effects of orientation deviation of a beam splitter and a reference mirror on the stability of a two-interferometer-based handheld FFOCT imaging probe.

In this work, we present a handheld full-field optical coherence tomography (FFOCT) system based on a series connection of two interferometers: the Michelson interferometer is used as a compensation part and the Fizeau interferometer is used as a detection part. Owing to the common-path arrangement of the Fizeau interferometer, this handheld FFOCT system has a compact detection arm and is insensitive to the external disturbance. A high-output halogen lamp and high NA microscope objective contribute to achieving the spatial resolution of 0.7µm×0.5µm (transverse × axial). Low imaging stability is caused by an extremely short coherence length. We found that to generate en face images with high quality and high stability using a probe with an extremely short coherence length, the range of deviation of the orientation of the beam splitter must be less than 1°, and the range of orientation deviation of the mirror in the Michelson interferometer corresponds to the displacement between the two field stop images at a distance not to exceed 10 µm.

Feature Channel Expansion and Background Suppression as the Enhancement for Infrared Pedestrian Detection.

Pedestrian detection is an important task in many intelligent systems, particularly driver assistance systems. Recent studies on pedestrian detection in infrared (IR) imagery have employed data-driven approaches. However, two problems in deep learning-based detection are the implicit performance and time-consuming training. In this paper, a novel channel expansion technique based on feature fusion is proposed to enhance the IR imagery and accelerate the training process. Besides, a novel background suppression method is proposed to stimulate the attention principle of human vision and shrink the region of detection. A precise fusion algorithm is designed to combine the information from different visual saliency maps in order to reduce the effect of truncation and miss detection. Four different experiments are performed from various perspectives in order to gauge the efficiency of our approach. The experimental results show that the Mean Average Precisions (mAPs) of four different datasets have been increased by 5.22% on average. The results prove that background suppression and suitable feature expansion will accelerate the training process and enhance the performance of IR image-based deep learning models.

Multi-omics analysis-based macrophage differentiation-associated papillary thyroid cancer patient classifier.

BACKGROUND: The reclassification of Papillary Thyroid Carcinoma (PTC) is an area of research that warrants attention. The connection between thyroid cancer, inflammation, and immune responses necessitates considering the mechanisms of differential prognosis of thyroid tumors from an immunological perspective. Given the high adaptability of macrophages to environmental stimuli, focusing on the differentiation characteristics of macrophages might offer a novel approach to address the issues related to PTC subtyping. METHODS: Single-cell RNA sequencing data of medullary cells infiltrated by papillary thyroid carcinoma obtained from public databases was subjected to dimensionality reduction clustering analysis. The RunUMAP and FindAllMarkers functions were utilized to identify the gene expression matrix of different clusters. Cell differentiation trajectory analysis was conducted using the Monocle R package. A complex regulatory network for the classification of Immune status and Macrophage differentiation-associated Papillary Thyroid Cancer Classification (IMPTCC) was constructed through quantitative multi-omics analysis. Immunohistochemistry (IHC) staining was utilized for pathological histology validation. RESULTS: Through the integration of single-cell RNA and bulk sequencing data combined with multi-omics analysis, we identified crucial transcription factors, immune cells/immune functions, and signaling pathways. Based on this, regulatory networks for three IMPTCC clusters were established. CONCLUSION: Based on the co-expression network analysis results, we identified three subtypes of IMPTCC: Immune-Suppressive Macrophage differentiation-associated Papillary Thyroid Carcinoma Classification (ISMPTCC), Immune-Neutral Macrophage differentiation-associated Papillary Thyroid Carcinoma Classification (INMPTCC), and Immune-Activated Macrophage differentiation-associated Papillary Thyroid Carcinoma Classification (IAMPTCC). Each subtype exhibits distinct metabolic, immune, and regulatory characteristics corresponding to different states of macrophage differentiation.

How can we establish animal models of HIV-associated lymphoma?

Human immunodeficiency virus (HIV) infection is strongly associated with a heightened incidence of lymphomas. To mirror the natural course of human HIV infection, animal models have been developed. These models serve as valuable tools to investigate disease pathobiology, assess antiretroviral and immunomodulatory drugs, explore viral reservoirs, and develop eradication strategies. However, there are currently no validated in vivo models of HIV-associated lymphoma (HAL), hampering progress in this crucial domain, and scant attention has been given to developing animal models dedicated to studying HAL, despite their pivotal role in advancing knowledge. This review provides a comprehensive overview of the existing animal models of HAL, which may enhance our understanding of the underlying pathogenesis and approaches for malignancies linked to HIV infection.

Data-driven discovery of innate immunomodulators via machine learning-guided high throughput screening.

The innate immune response is vital for the success of prophylactic vaccines and immunotherapies. Control of signaling in innate immune pathways can improve prophylactic vaccines by inhibiting unfavorable systemic inflammation and immunotherapies by enhancing immune stimulation. In this work, we developed a machine learning-enabled active learning pipeline to guide in vitro experimental screening and discovery of small molecule immunomodulators that improve immune responses by altering the signaling activity of innate immune responses stimulated by traditional pattern recognition receptor agonists. Molecules were tested by in vitro high throughput screening (HTS) where we measured modulation of the nuclear factor κ-light-chain-enhancer of activated B-cells (NF-κB) and the interferon regulatory factors (IRF) pathways. These data were used to train data-driven predictive models linking molecular structure to modulation of the NF-κB and IRF responses using deep representational learning, Gaussian process regression, and Bayesian optimization. By interleaving successive rounds of model training and in vitro HTS, we performed an active learning-guided traversal of a 139 998 molecule library. After sampling only ∼2% of the library, we discovered viable molecules with unprecedented immunomodulatory capacity, including those capable of suppressing NF-κB activity by up to 15-fold, elevating NF-κB activity by up to 5-fold, and elevating IRF activity by up to 6-fold. We extracted chemical design rules identifying particular chemical fragments as principal drivers of specific immunomodulation behaviors. We validated the immunomodulatory effect of a subset of our top candidates by measuring cytokine release profiles. Of these, one molecule induced a 3-fold enhancement in IFN-ß production when delivered with a cyclic di-nucleotide stimulator of interferon genes (STING) agonist. In sum, our machine learning-enabled screening approach presents an efficient immunomodulator discovery pipeline that has furnished a library of novel small molecules with a strong capacity to enhance or suppress innate immune signaling pathways to shape and improve prophylactic vaccination and immunotherapies.

Discovery of New States of Immunomodulation for Vaccine Adjuvants via High Throughput Screening: Expanding Innate Responses to PRRs.

Stimulation of the innate immune system is crucial in both effective vaccinations and immunotherapies. This is often achieved through adjuvants, molecules that usually activate pattern recognition receptors (PRRs) and stimulate two innate immune signaling pathways: the nuclear factor kappa-light-chain-enhancer of activated B-cells pathway (NF-κB) and the interferon regulatory factors pathway (IRF). Here, we demonstrate the ability to alter and improve adjuvant activity via the addition of small molecule "immunomodulators". By modulating signaling activity instead of receptor binding, these molecules allow the customization of select innate responses. We demonstrate both inhibition and enhancement of the products of the NF-κB and IRF pathways by several orders of magnitude. Some modulators apply generally across many receptors, while others focus specifically on individual receptors. Modulators boost correlates of a protective immune responses in a commercial flu vaccine model and reduced correlates of reactogenicity in a typhoid vaccine model. These modulators have a range of applications: from adjuvanticity in prophylactics to enhancement of immunotherapy.

Assessing the threshold effects of road infrastructure construction on farmland use transition: an empirical study in China.

China's rapid road infrastructure construction (RIC) occupies farmland and promotes the flow of rural development factors, which causes farmland use transition (FUT). Although prior research on RIC and their impact on FUT has attracted considerable attention, few studies have investigated the threshold effect of RIC on FUT. Threshold effect is the phenomenon that when the level of RIC reaches a certain critical value, the level of FUT changes abruptly. This paper uses China's provincial panel data from 2004 to 2018 to evaluate FUT. We also consider the spatial spillover effect of RIC and construct a panel threshold regression model to assess the impact of RIC on FUT. The results demonstrate that, considering the spatial spillover effect, RIC significantly promotes FUT, and the threshold effect first rises and then falls. Also, the threshold effect of RIC on FUT also has significant regional heterogeneity. There is a significant single threshold effect for RIC in central and western China, with threshold values of 0.90 and 0.84, respectively, while the spatial lag of RIC in eastern China has a single threshold with a value of 1.10. Our research indicates that the Chinese central government should promote the synergistic increase in RIC and sustainable farmland use by improving the accessibility of road infrastructure and basing RIC planning on the actual development needs of the region.

Functionalized Spiral-Rolling Millirobot for Upstream Swimming in Blood Vessel.

Untethered small robots with multiple functions show considerable potential as next-generation catheter-free systems for biomedical applications. However, owing to dynamic blood flow, even effective upstream swimming in blood vessels remains a challenge for the robot, let alone performing medical tasks. This paper presents an untethered millirobot with a streamlined shape that integrates the engine, delivery, and biopsy modules. Based on the proposed spiral-rolling strategy, this robot can move upstream at a record-breaking speed of ≈14 mm s-1 against a blood phantom flow of 136 mm s-1 . Moreover, benefiting from the bioinspired self-sealing orifice and easy-open auto-closed biopsy needle sheath, this robot facilitates several biomedical tasks in blood vessels, such as in vivo drug delivery, tissue and liquid biopsy, and cell transportation in rabbit arteries. This study will benefit the development of wireless millirobots for controllable, minimally invasive, highly integrated, and multifunctional endovascular interventions and will inspire new designs of miniature devices for biomedical applications.

Circular RNA circEIF3I promotes papillary thyroid carcinoma progression through competitively binding to miR-149 and upregulating KIF2A expression.

Circular RNAs (circRNAs) have been shown to regulate the development and progression of various cancers. However, the expression and function of circRNAs in papillary thyroid cancer (PTC) remain largely unknown. This study is aimed to investigate the potential roles of circEIF3I in PTC and elucidate the functional mechanism. We found that the expression of circEIF3I was significantly upregulated in PTC tissues compared to adjacent normal tissues. CircEIF3I expression was positively associated with tumor size, TNM stage and metastasis. CircEIF3I knockdown remarkably suppressed the proliferation, migration and invasion of PTC cells. Mechanistically, circEIF3I promoted KIF2A expression through competitively interacting with miR-149. In conclusion, circEIF3I upregulation in PTC tissues facilitates KIF2A expression by inhibiting miR-149, leading to malignant progression of PTC. This study suggested circEIF3I/miR-149/KIF2A axis might be a potential therapeutic target.

The Role of Exosomes in Thyroid Cancer and Their Potential Clinical Application.

The incidence of thyroid cancer (TC) is rapidly increasing worldwide. The diagnostic accuracy and dynamics of TC need to be improved, and traditional treatments are not effective enough for patients with poorly differentiated thyroid cancer. Exosomes are membrane vesicles secreted specifically by various cells and are involved in intercellular communication. Recent studies have shown that exosomes secreted by TC cells contribute to tumor progression, angiogenesis and metastasis. Exosomes in liquid biopsies can reflect the overall molecular information of tumors, and have natural advantages in diagnosing TC. Exosomes also play an important role in tumor therapy due to their special physicochemical properties. TC patients will benefit as more exosome patterns are discovered. In this review, we discuss the role of TC-derived exosomes in tumorigenesis and development, and describe the application of exosomes in the diagnosis and treatment of TC.

Liquid chromatography/quadrupole time-of-flight mass spectrometry for determination of saxitoxin and decarbamoylsaxitoxin in shellfish.

Saxitoxin (STX) and decarbamoylsaxitoxin (dcSTX) were determined by liquid chromatography with quadrupole time-of-flight mass spectrometry (Q-TOF MS). A shellfish tissue was extracted with 0.1 mol/l HCl under ultrasonication, and cleanup of extract was accomplished by solid-phase extraction with a C18 cartridge. Chromatographic separation was carried out on a C18 column (150 mm x 2.1 mm, 3.5 microm) with gradient elution of MeOH-H2O (20:80) containing 0.05% heptafluorobutyric acid and MeOH-H2O (15:85) containing 0.05% acetic acid. The protonated molecule [M + H]+ ions at m/z 257 for dcSTX and 300 for STX were selected in precursor ion scanning for Q-TOF MS in the positive electrospray ionizaion mode. Average recoveries and relative standard deviations, by analyzing samples spiked at a level of 0.1, 0.8 or 1.6 microg/g, were 84-92 and 8-14%, respectively. Identification of the presence of the toxins in shellfish tissues was based on the structural information offered by Q-TOF MS.

DKK3 is a potential tumor suppressor gene in papillary thyroid carcinoma.

The expression of the Dickkopf homolog 3 (DKK3) gene is downregulated in some human cancers, suggesting a possible tumor suppressor role of this gene. The role and regulation of DKK3 in thyroid cancer have not been examined. In this study, we explored the relationship of promoter methylation with the inactivation of DKK3 and tumor behaviors in papillary thyroid carcinoma (PTC). We used methylation-specific PCR and RT-PCR to examine the promoter methylation and expression of DKK3 and tumor characteristics. We found mRNA expression of DKK3 in 44.9% of the PTC tissue samples vs 100% of the matched normal thyroid tissue samples (P<0.01). In contrast, an opposite distribution pattern of DKK3 gene methylation was observed; specifically, 38.8% of the PTC tissue samples vs 0% of the matched normal thyroid tissue samples harbored DKK3 methylation. An inverse correlation between the promoter methylation and mRNA expression of DKK3 in PTC tissue samples was also observed. Moreover, we also found an inverse correlation between DKK3 expression and some aggressive pathological characteristics of PTC, including high TNM stages and lymph node metastasis, but a positive correlation between DKK3 promoter hypermethylation and pathological aggressiveness of the tumor. Treatment of the PTC cell line TPC-1 with the demethylating agent 5-azaC reduced DKK3 promoter methylation and enhanced its expression, establishing functionally the impact of DKK3 methylation on its expression. Our data thus for the first time demonstrate that the DKK3 gene is a potential tumor suppressor gene in thyroid cancer and that aberrant promoter methylation is an important mechanism for its downregulation, which may play a role in the tumorigenesis and aggressiveness of PTC.

[High performance liquid chromatography/quadrupole time-of-flight mass spectrometry for the determination of Brevetoxin PbTx-2 in shellfish].

Brevetoxin PbTx-2 was determined by high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (Q-TOFMS). Extraction from shellfish tissue was achieved with acetone, and purified by solid-phase extraction on a C18 cartridge column. Chromatographic separation was performed on a Zorbax XDB-C18 column(150 mm x 2.1 mm i.d., 3.5 microm) combined with a safeguard column (Symmetry C18, 20 mm i.d. x 3.9 mm, 5 microm) with methanol-water(85: 15, v/v) containing 0.5 mmol/L ammonium acetate as eluent at a flow rate of 0.20 mL/min. The protonated PbTx-2 molecule was selected as a precursor ion scanning for Q-TOFMS in the positive electrospray ionization mode. Average recoveries of PbTx-2 spiked to tissue homogenates through the complete cleanup procedure ranged from 91% to 94%, and relative standard deviations (RSD) ranged from 11% to 12%. The limit of quantification in shellfish tissue was 0.1 microg/g, and the limit of detection based on signal-to-noise ratio of 3 was 0.5 ng. The proposed method was used to confirm PbTx-2 in toxic shellfish. It offers a high degree of specificity because Q-TOFMS with high resolution permits accurate relative molecular mass and fragment ion measurement at no expense of sensitivity.