New insights into KLFs and SOXs in cancer pathogenesis, stemness, and therapy.

Despite the development of cancer therapies, the success of most treatments has been impeded by drug resistance. The crucial role of tumor cell plasticity has emerged recently in cancer progression, cancer stemness and eventually drug resistance. Cell plasticity drives tumor cells to reversibly convert their cell identity, analogous to differentiation and dedifferentiation, to adapt to drug treatment. This phenotypical switch is driven by alteration of the transcriptome. Several pluripotent factors from the KLF and SOX families are closely associated with cancer pathogenesis and have been revealed to regulate tumor cell plasticity. In this review, we particularly summarize recent studies about KLF4, KLF5 and SOX factors in cancer development and evolution, focusing on their roles in cancer initiation, invasion, tumor hierarchy and heterogeneity, and lineage plasticity. In addition, we discuss the various regulation of these transcription factors and related cutting-edge drug development approaches that could be used to drug "undruggable" transcription factors, such as PROTAC and PPI targeting, for targeted cancer therapy. Advanced knowledge could pave the way for the development of novel drugs that target transcriptional regulation and could improve the outcome of cancer therapy.

Role of caspase-11 non-canonical inflammasomes in retinal ischemia/reperfusion injury.

BACKGROUND: Retinal ischemia/reperfusion (IR) injury is a common pathological process in many ophthalmic diseases. Interleukin-1ß (IL-1ß) is an important inflammatory factor involved in the pathology of retinal IR injury, but the mechanism by which IL-1ß is regulated in such injury remains unclear. Caspase-11 non-canonical inflammasomes can regulate the synthesis and secretion of IL-1ß, but its role in retinal IR injury has not been elucidated. This study aimed to evaluate the role of caspase-11 non-canonical inflammasomes in retinal IR injury. METHODS: Retinal IR injury was induced in C57BL/6J mice by increasing the intraocular pressure to 110 mmHg for 60 min. The post-injury changes in retinal morphology and function and in IL-1ß expression were compared between caspase-11 gene knockout (caspase-11-/-) mice and wild-type (WT) mice. Morphological and functional changes were evaluated using hematoxylin-eosin staining and retinal whole mount staining and using electroretinography (ERG), respectively. IL-1ß expression in the retina was measured using enzyme-linked immunosorbent assay (ELISA). The levels of caspase-11-related protein were measured using western blot analysis. The location of caspase-11 in the retina was determined via immunofluorescence staining. Mouse type I astrocytes C8-D1A cells were used to validate the effects of caspase-11 simulation via hypoxia in vitro. Small-interfering RNA targeting caspase-11 was constructed. Cell viability was evaluated using the MTT assay. IL-1ß expression in supernatant and cell lysate was measured using ELISA. The levels of caspase-11-related protein were measured using western blot analysis. RESULTS: Retinal ganglion cell death and retinal edema were more ameliorated, and the ERG b-wave amplitude was better after retinal IR injury in caspase-11-/- mice than in WT mice. Further, caspase-11-/- mice showed lower protein expressions of IL-1ß, cleaved caspase-1, and gasdermin D (GSDMD) in the retina after retinal IR injury. Caspase-11 protein was expressed in retinal glial cells, and caspase-11 knockdown played a protective role against hypoxia in C8-D1A cells. The expression levels of IL-1ß, cleaved caspase-1, and GSDMD were inhibited after hypoxia in the si-caspase-11 constructed cells. CONCLUSIONS: Retinal IR injury activates caspase-11 non-canonical inflammasomes in glial cells of the retina. This results in increased protein levels of GSDMD and IL-1ß and leads to damage in the inner layer of the retina.

Visualization of Diabetes Progression by an Activatable NIR-IIb Luminescent Probe.

Developing NIR-IIb luminescence probes with rapid visualization and a high penetration depth is essential for diabetes research. Combining a sensitizing switch with lanthanide-doped nanoparticles (LnNPs) has been employed to fabricate the NIR-IIb probes. However, these probes mainly adopt heptamethine cyanine dye as the antenna, and the NIR-IIb signal is activated by inhibiting the photoinduced electron transfer (PET) of the dye. Due to limited recognition units, this strategy makes many biomolecules undetectable, such as cysteine (Cys), which is closely related to diabetes. Herein, in this article, hemicyanine dye, NFL-OH, was verified as a new antenna to sensitize NIR-IIb emission from LnNPs. Unlike traditional cyanine dyes, hemicyanine's fluorescence intensity can also be modulated by intramolecular charge transfer (ICT), thereby expanding the range of detectable targets for NIR-IIb probes based on sensitization mechanism. Through switching the hemicyanine-sensitized NIR-IIb emission, we successfully fabricated an NFL-Cys-LnNPs' nanoprobe, which can effectively monitor Cys concentration in the liver of diabetic mice during diabetes progression and evaluate the efficacy of diabetic drugs. Our work not only presents an excellent tool for Cys imaging but also introduces new concepts for designing NIR-IIb probes.

Magnetic Nanoparticle-Based Microfluidic Platform for Automated Enrichment of High-Purity Extracellular Vesicles.

Extracellular vesicles (EVs) are available in various biological fluids and have highly heterogeneous sizes, origins, contents, and functions. Rapid enrichment of high-purity EVs remains crucial for enhancing research on EVs in tumors. In this work, we present a magnetic nanoparticle-based microfluidic platform (ExoCPR) for on-chip isolation, purification, and mild recovery of EVs from cell culture supernatant and plasma within 29 min. The ExoCPR chip integrates bubble-driven micromixers and immiscible filtration assisted by surface tension (IFAST) technology. The bubble-driven micromixer enhances the mixing between immunomagnetic beads and EVs, eliminating the need for manual pipetting or off-chip oscillatory incubation. The high-purity EVs were obtained after passing through the immiscible phase interface where hydrophilic or hydrophobic impurities nonspecifically bound to SIMI were removed. The ExoCPR chip had a capture efficiency of 75.8% and a release efficiency of 62.7% for model EVs. We also demonstrated the powerful performance of the ExoCPR in isolating EVs from biological samples (>90% purity). This chip was further employed in clinical plasma samples and showed that the number of GPC3-positive EVs isolated from hepatocellular carcinoma patients was significantly higher than that of healthy individuals. This ExoCPR chip may provide a promising tool for EV-based liquid biopsy and other fundamental research.

Effect of Cerium on Inclusion Evolution and Pitting Corrosion of Nb-Microalloyed Steel.

Nb-microalloyed steels are widely used in construction engineering fields due to their excellent mechanical properties, but they face serious corrosion problems in service environments. Pitting corrosion is the severest form of corrosion, and the types of inclusions are the leading cause to induce pitting corrosion. A new strategy is proposed to enhance the corrosion resistance of steels by achieving a beneficial transformation of inclusions with Ce treatment. In this paper, two types of Nb-microalloyed steels (0% Ce and 0.0058% Ce steel) were prepared to study the modification effect on inclusions in industrial production. The spherical CaS•C12A7 inclusions were modified to smaller ellipsoidal Ce2O2S inclusions, and the proportion of inclusions (0-2 µm) increased significantly from 27 to 66%, while large inclusions (>6 µm) disappeared. A kinetic model of inclusion evolution was established. The results of electrochemical tests indicated that the corrosion potential was positively shifted, and the corrosion current was reduced after Ce treatment. Additionally, the number of defects in the passivation film was decreased, and the corrosion resistance of the steel was significantly improved. The addition of Ce changed the types of inclusions and reduced the number of pitting nucleation points, which led to a remarkable reduction in the number and size of pitting pits. The mechanism of pitting corrosion induced by different types of inclusions was further investigated, and a pitting corrosion model was modeled based on the immersion experiments. Research results provide theoretical support for enhancing the corrosion resistance of steel.

HFM-Tracker: a cell tracking algorithm based on hybrid feature matching.

Cell migration is known to be a fundamental biological process, playing an essential role in development, homeostasis, and diseases. This paper introduces a cell tracking algorithm named HFM-Tracker (Hybrid Feature Matching Tracker) that automatically identifies cell migration behaviours in consecutive images. It combines Contour Attention (CA) and Adaptive Confusion Matrix (ACM) modules to accurately capture cell contours in each image and track the dynamic behaviors of migrating cells in the field of view. Cells are firstly located and identified via the CA module-based cell detection network, and then associated and tracked via a cell tracking algorithm employing a hybrid feature-matching strategy. This proposed HFM-Tracker exhibits superiorities in cell detection and tracking, achieving 75% in MOTA (Multiple Object Tracking Accuracy) and 65% in IDF1 (ID F1 score). It provides quantitative analysis of the cell morphology and migration features, which could further help in understanding the complicated and diverse cell migration processes.

The Role of Angiotensin II Receptor Blockers in the Management of Hypertrophic Cardiomyopathy: An Updated Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: The use of angiotensin II receptor blockers (ARBs) in the treatment of hypertrophic cardiomyopathy (HCM) remains a subject of controversy. METHODS: We conducted a comprehensive search of the Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov, and Web of Science databases until October 2023 to identify articles investigating the effects of ARBs in patients diagnosed with HCM. Predefined criteria were utilized for selecting data on study characteristics and results. RESULTS: The study included a total of 387 patients from 6 randomized controlled trials, which were reported in 7 articles. The results of the meta-analysis revealed that the utilization of ARBs did not yield a reduction in left ventricular (LV) mass (p = 0.07) and maximum LV wall thickness (p = 0.25), nor did it demonstrate any improvement in LV fibrosis (p = 0.39). Furthermore, there was no significant impact observed on early diastolic mitral annular velocity (p = 0.19) and LV ejection fraction (p = 0.44). CONCLUSIONS: The administration of ARBs does not appear to yield improvements in cardiac structure, function, and myocardial fibrosis in patients with HCM.

Self-amplifying loop of NF-κB and periostin initiated by PIEZO1 accelerates mechano-induced senescence of nucleus pulposus cells and intervertebral disc degeneration.

Abnormal mechanical load is a main risk factor of intervertebral disc degeneration (IDD), and cellular senescence is a pathological change in IDD. In addition, extracellular matrix (ECM) stiffness promotes human nucleus pulposus cells (hNPCs) senescence. However, the molecular mechanism underlying mechano-induced cellular senescence and IDD progression is not yet fully elucidated. First, we demonstrated that mechano-stress promoted hNPCs senescence via NF-κB signaling. Subsequently, we identified periostin as the main mechano-responsive molecule in hNPCs through unbiased sequencing, which was transcriptionally upregulated by NF-κB p65; moreover, secreted periostin by senescent hNPCs further promoted senescence and upregulated the catabolic process in hNPCs through activating NF-κB, forming a positive loop. Both Postn (encoding periostin) knockdown via siRNA and periostin inactivation via neutralizing antibodies alleviated IDD and NPCs senescence. Furthermore, we found that mechano-stress initiated the positive feedback of NF-κB and periostin via PIEZO1. PIEZO1 activation by Yoda1 induced severe IDD in rat tails without compression, and Postn knockdown alleviated the Yoda1-induced IDD in vivo. Here, we reported for the first time that self-amplifying loop of NF-κB and periostin initiated via PIEZO1 under mechano-stress accelerated NPCs senescence, leading to IDD. Furthermore, periostin neutralizing antibodies, which may serve as potential therapeutic agents for IDD, interrupted this loop.

Enhancing the clinical diagnosis of the acute and subacute phases of autoimmune encephalitis and predicting the risk factors: the potential advantages of 18F-FDG PET/CT.

BACKGROUND: 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (18F-FDG PET) could help evaluate metabolic abnormalities by semi-quantitative measurement to identify autoimmune encephalitis (AE). Few studies have been conducted to analyze the prognostic factors of AE. The study aimed to explore the values of diagnosis and treatment evaluation by 18F-FDG PET and preliminarily discussed the potential value in predicting the prognosis of AE patients. METHODS: AE patients underwent 18F-FDG PET/CT and magnetic resonance imaging (MRI). There were two steps to analyse 18F-FDG PET imaging data. The first step was visual assessment. The second step was to analyse 18F-FDG PET parameters using Scenium software (Siemens Molecular Imaging Ltd). The mean standardized uptake value (SUVmean) and maximum standardized uptake value (SUVmax) of brain relative regional metabolism (BRRM) were quantified in the case and control groups according to the anatomical automatic labeling (AAL) partition. The main statistical method was the Kruskal-Wallis test. Finally, the simple linear regression method was used to analyse the relationships between 18F-FDG PET parameters and the modified Rankin Scale (mRS) scores before and after treatment. RESULTS: The results on 18F-FDG PET showed that visual assessment abnormalities were in the mesial temporal lobe (MTL) (70.8%), (mainly infringing on the hippocampus and amygdala), basal ganglia (62.5%), frontal lobes (37.5%), occipital lobes (29.2%), and parietal lobes (12.5%). The positive rate of abnormalities on 18F-FDG PET was more sensitive than that on MRI (95.5% vs 32.2%, p = 0.001). The number of lesions on PET was positively correlated with the mRS scores before and after treatment, and the correlation before treatment was more significant. Before treatment, the SUVmean of the left occipital lobe was the most remarkable (SUVmean, R2 = 0.082, p > 0.05) factor associated with the mRS score, and the correlation was negative. With regard to prognosis, the SUVmax of the MTL was the most notable (R2 = 0.1471, p > 0.05) factor associated with the mRS score after treatment, and the correlation was positive. CONCLUSIONS: 18F-FDG PET could be more sensitive and informative than MRI in the early phases of AE. The common pattern of AE was high MTL metabolism on 18F-FDG PET, which was associated with hypometabolism of the occipital lobe, and the number of lesions on PET before treatment may be significant factors in assessing disease severity. The SUVmax of MTL hypermetabolism may serve as a prognostic biomarker in AE.

Can a Nomogram Predict Survival After Treatment for an Ankylosing Spondylitis Cervical Fracture in a Patient With Neurologic Impairment? A National, Multicenter Study.

BACKGROUND: Ankylosing spondylitis-related cervical spine fracture with neurologic impairment (ASCF-NI) is a rare but often lethal injury. Factors independently associated with survival after treatment remain poorly defined, and identifying patients who are likely to survive the injury remains challenging. QUESTIONS/PURPOSES: (1) What factors are independently associated with survival after treatment among patients with ASCF-NI? (2) Can a nomogram be developed that is sufficiently simple for clinicians to use that can identify patients who are the most likely to survive after injury? METHODS: This retrospective study was conducted based on a multi-institutional group of patients admitted and treated at one of 29 tertiary hospitals in China between March 1, 2003, and July 31, 2019. A total of 363 patients with a mean age of 53 ± 12 years were eventually included, 343 of whom were male. According to the National Household Registration Management System, 17% (61 of 363) died within 5 years of injury. Patients were treated using nonsurgical treatment or surgery, including procedures using the anterior approach, posterior approach, or combined anterior and posterior approaches. Indications for surgery included three-column injury, unstable fracture displacement, neurologic impairment or continuous progress, and intervertebral disc incarceration. By contrast, patients generally received nonsurgical treatment when they had a relatively stable fracture or medical conditions that did not tolerate surgery. Demographic, clinical, and treatment data were collected. The primary study goal was to identify which factors are independently associated with death within 5 years of injury, and the secondary goal was the development of a clinically applicable nomogram. We developed a multivariable Cox hazards regression model, and independent risk factors were defined by backward stepwise selection with the Akaike information criterion. We used these factors to create a nomogram using a multivariate Cox proportional hazards regression analysis. RESULTS: After controlling for potentially confounding variables, we found the following factors were independently associated with a lower likelihood of survival after injury: lower fracture site, more-severe peri-injury complications, poorer American Spinal Injury Association (ASIA) Impairment Scale, and treatment methods. We found that a C5 to C7 or T1 fracture (ref: C1 to C4 and 5; hazard ratio 1.7 [95% confidence interval 0.9 to 3.5]; p = 0.12), moderate peri-injury complications (ref: absence of or mild complications; HR 6.0 [95% CI 2.3 to 16.0]; p < 0.001), severe peri-injury complications (ref: absence of or mild complications; HR 30.0 [95% CI 11.5 to 78.3]; p < 0.001), ASIA Grade A (ref: ASIA Grade D; HR 2.8 [95% CI 1.1 to 7.0]; p = 0.03), anterior approach (ref: nonsurgical treatment; HR 0.5 [95% CI 0.2 to 1.0]; p = 0.04), posterior approach (ref: nonsurgical treatment; HR 0.4 [95% CI 0.2 to 0.8]; p = 0.006), and combined anterior and posterior approach (ref: nonsurgical treatment; HR 0.4 [95% CI 0.2 to 0.9]; p = 0.02) were associated with survival. Based on these factors, a nomogram was developed to predict the survival of patients with ASCF-NI after treatment. Tests revealed that the developed nomogram had good performance (C statistic of 0.91). CONCLUSION: The nomogram developed in this study will allow us to classify patients with different mortality risk levels into groups. This, coupled with the factors we identified, was independently associated with survival, and can be used to guide more appropriate treatment and care strategies for patients with ASCF-NI. LEVEL OF EVIDENCE: Level III, therapeutic study.

Sleep bruxism events: an epiphenomenon of severe obstructive sleep apnea?

OBJECTIVES: This study investigated the temporal relationships between apnea-hypopnea (AH) and sleep bruxism (SB) events and correlated SB to various respiratory/sleep indexes in adult patients with concomitant obstructive sleep apnea (OSA) and SB. MATERIALS AND METHODS: Nocturnal PSG data of 147 consecutive OSA patients were examined for comorbid SB. Among the 49 subjects with coexisting OSA and SB, 26 were randomly selected for in-depth appraisal of temporal patterns which were classified as T1 (unrelated activities), T2 (AH events occur before SB events), T3 (SB events occur before AH events), and T4 (AH and SB events occur simultaneously). Data were analyzed using Mann-Whitney U tests and Spearman's correlation (α = 0.05). RESULTS: The majority (84.5%) of AH events were unrelated to SB events. Of the 15.5% of related activities, T2 and T3 patterns occurred in 14.1% and 1.4%, respectively. SB events/index, the percentage of unrelated/related AH-SB events, and T2-T3 episodes were not associated with gender, age, body mass (BMI), and apnea-hypopnea (AHI) index. SB events were related to total sleep time (rs = 0.44), but no significant associations were discerned between SB and AH index. CONCLUSIONS: As most AH events were unrelated to SB events, OSA and SB are probably epiphenomena in adult patients with concomitant conditions. Where AH-SB events were related, the T2 temporal pattern, where SB events were subsequent to AH events, featured predominantly alluding to a specific form of secondary SB triggered by sleep micro-arousals. CLINICAL RELEVANCE: AH and SB events are probably epiphenomena in adult patients with coexisting OSA and SB. Even so, OSA patients should be routinely screened for SB and vice versa considering their frequent comorbidity.

WLiT: Windows and Linear Transformer for Video Action Recognition.

The emergence of Transformer has led to the rapid development of video understanding, but it also brings the problem of high computational complexity. Previously, there were methods to divide the feature maps into windows along the spatiotemporal dimensions and then calculate the attention. There are also methods to perform down-sampling during attention computation to reduce the spatiotemporal resolution of features. Although the complexity is effectively reduced, there is still room for further optimization. Thus, we present the Windows and Linear Transformer (WLiT) for efficient video action recognition, by combining Spatial-Windows attention with Linear attention. We first divide the feature maps into multiple windows along the spatial dimensions and calculate the attention separately inside the windows. Therefore, our model further reduces the computational complexity compared with previous methods. However, the perceptual field of Spatial-Windows attention is small, and global spatiotemporal information cannot be obtained. To address this problem, we then calculate Linear attention along the channel dimension so that the model can capture complete spatiotemporal information. Our method achieves better recognition accuracy with less computational complexity through this mechanism. We conduct extensive experiments on four public datasets, namely Something-Something V2 (SSV2), Kinetics400 (K400), UCF101, and HMDB51. On the SSV2 dataset, our method reduces the computational complexity by 28% and improves the recognition accuracy by 1.6% compared to the State-Of-The-Art (SOTA) method. On the K400 and two other datasets, our method achieves SOTA-level accuracy while reducing the complexity by about 49%.

MSFFAL: Few-Shot Object Detection via Multi-Scale Feature Fusion and Attentive Learning.

Few-shot object detection (FSOD) is proposed to solve the application problem of traditional detectors in scenarios lacking training samples. The meta-learning methods have attracted the researchers' attention for their excellent generalization performance. They usually select the same class of support features according to the query labels to weight the query features. However, the model cannot possess the ability of active identification only by using the same category support features, and feature selection causes difficulties in the testing process without labels. The single-scale feature of the model also leads to poor performance in small object detection. In addition, the hard samples in the support branch impact the backbone's representation of the support features, thus impacting the feature weighting process. To overcome these problems, we propose a multi-scale feature fusion and attentive learning (MSFFAL) framework for few-shot object detection. We first design the backbone with multi-scale feature fusion and channel attention mechanism to improve the model's detection accuracy on small objects and the representation of hard support samples. Based on this, we propose an attention loss to replace the feature weighting module. The loss allows the model to consistently represent the objects of the same category in the two branches and realizes the active recognition of the model. The model no longer depends on query labels to select features when testing, optimizing the model testing process. The experiments show that MSFFAL outperforms the state-of-the-art (SOTA) by 0.7-7.8% on the Pascal VOC and exhibits 1.61 times the result of the baseline model in MS COCO's small objects detection.

Precise evaluation of blood flow patterns in human carotid bifurcation based on high-frame-rate vector flow imaging.

PURPOSE: To investigate the feasibility of high-frame-rate vector flow imaging (HiFR-VFI) compared to ultrasound color Doppler flow imaging (CDFI) for precisely evaluating flow characteristics in the carotid bifurcation (CB) of presumed healthy adults. METHODS: Forty-three volunteers were assessed for flow characteristics and their extensions using HiFR-VFI and CDFI in CBs. The flow patterns were classified according to the streamlines in HiFR-VFI and quantitatively measured using an innovative turbulence index (Tur-value). Interobserver agreement was also assessed. RESULTS: HiFR-VFI was consistent with CDFI in detecting laminar and nonlaminar flow in 81.4% of the cases; however, in 18.6% of the cases, only HiFR-VFI identified the nonlaminar flow. HiFR-VFI showed a larger extension of complex flow (0.37 ± 0.26 cm2 ) compared to CDFI (0.22 ± 0.21 cm2 ; p < 0.05). The flow patterns were classified into four types: 3 type-I (laminar flow), 35 type-II (rotational flow), 27 type-III (reversed flow), and 5 type-IV (complex flow). The Tur-value of type-IV (50.03 ± 14.97)% is larger than type-III (44.57 ± 8.89)%, type-II (16.30 ± 8.16)%, and type-I (1.48 ± 1.43)% (p < 0.05). Two radiologists demonstrated almost perfect interobserver agreement on recognizing the change of streamlines (κ = 0.81, p < 0.001). The intraclass correlation coefficient of the Tur-value was 0.98. CONCLUSION: HiFR-VFI can reliably characterize complex hemodynamics with quantitative turbulence measurement and may be an auxiliary diagnostic tool for assessing atherosclerotic arterial disease.

Stem Cells for Cancer Therapy: Translating the Uncertainties and Possibilities of Stem Cell Properties into Opportunities for Effective Cancer Therapy.

Cancer recurrence and drug resistance following treatment, as well as metastatic forms of cancer, are trends that are commonly encountered in cancer management. Amidst the growing popularity of personalized medicine and targeted therapy as effective cancer treatment, studies involving the use of stem cells in cancer therapy are gaining ground as promising translational treatment options that are actively pursued by researchers due to their unique tumor-homing activities and anti-cancer properties. Therefore, this review will highlight cancer interactions with commonly studied stem cell types, namely, mesenchymal stroma/stem cells (MSC), induced pluripotent stem cells (iPSC), iPSC-derived MSC (iMSC), and cancer stem cells (CSC). A particular focus will be on the effects of paracrine signaling activities and exosomal miRNA interaction released by MSC and iMSCs within the tumor microenvironment (TME) along with their therapeutic potential as anti-cancer delivery agents. Similarly, the role of exosomal miRNA released by CSCs will be further discussed in the context of its role in cancer recurrence and metastatic spread, which leads to a better understanding of how such exosomal miRNA could be used as potential forms of non-cell-based cancer therapy.

Synthesis, Crystal Structure, Antibacterial and In Vitro Anticancer Activity of Novel Macroacyclic Schiff Bases and Their Cu (II) Complexes Derived from S-Methyl and S-Benzyl Dithiocarbazate.

A series of novel macroacyclic Schiff base ligands and their Cu (II) complexes were synthesised via reacting dicarbonyls of varying chain lengths with S-methyl dithiocarbazate (SMDTC) and S-benzyl dithiocarbazate (SBDTC) followed by coordination with Cu (II) ions. X-ray crystal structures were obtained for compound 4, an SBDTC-diacetyl analogue, and Cu7, an SMDTC-hexanedione Cu (II) complex. Anticancer evaluation of the compounds showed that Cu1, an SMDTC-glyoxal complex, demonstrated the highest cytotoxic activity against MCF-7 and MDA-MB-231 breast cancer cells with IC50 values of 1.7 µM and 1.4 µM, respectively. There was no clear pattern observed between the effect of chain length and cytotoxic activity; however, SMDTC-derived analogues were more active than SBDTC-derived analogues against MDA-MB-231 cells. The antibacterial assay showed that K. rhizophila was the most susceptible bacteria to the compounds, followed by S. aureus. Compound 4 and the SMDTC-derived analogues 3, 5, Cu7 and Cu9 possessed the highest antibacterial activity. These active analogues were further assessed, whereby 3 possessed the highest antibacterial activity with an MIC of <24.4 µg/mL against K. rhizophila and S. aureus. Further antibacterial studies showed that at least compounds 4 and 5 were bactericidal. Thus, Cu1 and 3 were the most promising anticancer and antibacterial agents, respectively.

Alternate thermal stimulation ameliorates thermal sensitivity and modulates calbindin-D 28K expression in lamina I and II and dorsal root ganglia in a mouse spinal cord contusion injury model.

Neuropathic pain (NP) is a common complication that negatively affects the lives of patients with spinal cord injury (SCI). The disruption in the balance of excitatory and inhibitory neurons in the spinal cord dorsal horn contributes to the development of SCI and induces NP. The calcium-binding protein (CaBP) calbindin-D 28K (CaBP-28K) is highly expressed in excitatory interneurons, and the CaBP parvalbumin (PV) is present in inhibitory neurons in the dorsal horn. To better define the changes in the CaBPs contributing to the development of SCI-induced NP, we examined the changes in CaBP-28K and PV staining density in the lumbar (L4-6) lamina I and II, and their relationship with NP after mild spinal cord contusion injury in mice. We additionally examined the effects of alternate thermal stimulation (ATS). Compared with sham mice, injured animals developed mechanical allodynia in response to light mechanical stimuli and exhibited mechanical hyporesponsiveness to noxious mechanical stimuli. The decreased response latency to heat stimuli and increased response latency to cold stimuli at 7 days post injury suggested that the injured mice developed heat hyperalgesia and cold hypoalgesia, respectively. Temperature preference tests showed significant warm allodynia after injury. Animals that underwent ATS (15-18 and 35-40°C; +5 minutes/stimulation/day; 5 days/week) displayed significant amelioration of heat hyperalgesia, cold hypoalgesia, and warm allodynia after 2 weeks of ATS. In contrast, mechanical sensitivity was not influenced by ATS. Analysis of the CaBP-28K positive signal in L4-6 lamina I and II indicated an increase in staining density after SCI, which was associated with an increase in the number of CaBP-28K-stained L4-6 dorsal root ganglion (DRG) neurons. ATS decreased the CaBP-28K staining density in L4-6 spinal cord and DRG in injured animals, and was significantly and strongly correlated with ATS alleviation of pain behavior. The expression of PV showed no changes in lamina I and II after ATS in SCI animals. Thus, ATS partially decreases the pain behavior after SCI by modulating the changes in CaBP-associated excitatory-inhibitory neurons.

An ultra-low noise amplifier array system for high throughput single entity analysis.

Electrochemical measurements at the single entity level provide ultra-sensitive tools for the precise diagnosis and understanding of basic biological and chemical processes. By decoding current signatures, single-entity electrochemistry provides abundant information on charges, sizes, shapes, catalytic performances and compositions. The accuracy of single-entity electrochemistry highly relies on advanced instrumentation to achieve the amperometric resolution at the sub-picoampere level and the temporal resolution at the sub-microsecond level. Currently, it is still a challenge for paralleling amplifiers to allow low-noise and high bandwidth single-entity electrochemical measurements. Herein, we developed a low-noise four-channel electrochemical instrumentation that integrates an Au electrode array with amplifiers in the circuit board. With this amplifier array, we achieved a high bandwidth (>100 kHz) electrochemical measurement. The further practical experiments proved the capability of this amplifier array system in acquiring transient signals from both single-molecule detection with an aerolysin nanopore and single Pt nanoparticle catalysis during the dynamic collision process. Paired with appropriate microfluidic array systems, our instrumentation will enable an extraordinarily high-throughput feature for single-entity sensing.

Elevated serum triglyceride levels may be a key independent predicting factor for gallbladder cancer risk in gallbladder stone disease patients: a case-control study.

BACKGROUND: Gallbladder stone diseases (GSD) is a main risk factor of gallbladder cancer (GBC). This study aimed to reveal their bridge to metabolic syndrome. MATERIAL/METHOD: The clinical and experimental data of 2210 GBC patients, from 3524 Chinese patients, in our hospital from Jan. 2009 to Dec. 2020 were summarized. The metabolic syndrome indexes, influencing factors for both GBC and GSD, were analyzed by unconditional logistic regression in this case-control study. RESULT: There were significantly higher morbidity of GBC in the overall, GSD and non-GSD with hypertriglyceridemia patients versus non-hypertriglyceridemia ones (P < 0.001, all). In GSD patients, univariate regression showed a significantly positive correlation between serum triglyceride (TG), low density lipoprotein cholesterol (LDL-c), fasting insulin (FINS) levels, Homeostasis model assessment-insulin resistance (HOMA-IR), female being, body mass index, hypertriglyceridemia and hazard of GBC with GSD (P < 0.001, all), and a significantly negative correlation to systolic pressure (SBP), diastolic pressure (DBP), hypertension and high-density lipoprotein cholesterol (HDL-c), fasting blood glucose (FBG) (P < 0.05, all); multivariate regression showed that serum triglyceride was the most significantly positive factor associated to GBC (P < 0.001, all) among the hazard factors including serum TG, LDL-c levels, HOMA-IR. In non-GSD ones, multivariate regression showed that HOMA-IR was the most significantly positive factor associated to GBC among the hazard factors including serum TG, LDL-c levels, HOMA-IR, female being, while DM had a significantly inversion negative association (P < 0.001). CONCLUSION: We found initially that elevated serum TG levels could be the most remarkable independent predicting factor for GBC risk with GSD, while insulin resistance might act as the first one in non-GSD. More importantly, we advocated initially the sharp rise of serum TG levels as the potential of a candidate diagnostic or prognostic biomarker of GBC with GSD. TRIAL REGISTRATION: The study may be performed in accordance with the ethical standards provided by the responsible committee of our institution (First Affiliated Hospital of Xi'an Jiaotong University. XJTU1AF2020LSK-160) at which the work was carried out an in accordance with the Declaration of Helsinki. The ethics committee of our institution strictly comply with the requirements of ICH-GCP、GCP and relevant regulations to construct, operate and implement operating procedures.

Non-destructive state detection for quantum logic spectroscopy of molecular ions.

Precision laser spectroscopy of cold and trapped molecular ions is a powerful tool in fundamental physics--used, for example, in determining fundamental constants, testing for their possible variation in the laboratory, and searching for a possible electric dipole moment of the electron. However, the absence of cycling transitions in molecules poses a challenge for direct laser cooling of the ions, and for controlling and detecting their quantum states. Previously used state-detection techniques based on photodissociation or chemical reactions are destructive and therefore inefficient, restricting the achievable resolution in laser spectroscopy. Here, we experimentally demonstrate non-destructive detection of the quantum state of a single trapped molecular ion through its strong Coulomb coupling to a well controlled, co-trapped atomic ion. An algorithm based on a state-dependent optical dipole force changes the internal state of the atom according to the internal state of the molecule. We show that individual quantum states in the molecular ion can be distinguished by the strength of their coupling to the optical dipole force. We also observe quantum jumps (induced by black-body radiation) between rotational states of a single molecular ion. Using the detuning dependence of the state-detection signal, we implement a variant of quantum logic spectroscopy of a molecular resonance. Our state-detection technique is relevant to a wide range of molecular ions, and could be applied to state-controlled quantum chemistry and to spectroscopic investigations of molecules that serve as probes for interstellar clouds.