Revealing molecular and cellular heterogeneity in hypopharyngeal carcinogenesis through single-cell RNA and TCR/BCR sequencing.

Introduction: Hypopharyngeal squamous cell carcinoma (HSCC) is one of the malignant tumors with the worst prognosis in head and neck cancers. The transformation from normal tissue through low-grade and high-grade intraepithelial neoplasia to cancerous tissue in HSCC is typically viewed as a progressive pathological sequence typical of tumorigenesis. Nonetheless, the alterations in diverse cell clusters within the tissue microenvironment (TME) throughout tumorigenesis and their impact on the development of HSCC are yet to be fully understood. Methods: We employed single-cell RNA sequencing and TCR/BCR sequencing to sequence 60,854 cells from nine tissue samples representing different stages during the progression of HSCC. This allowed us to construct dynamic transcriptomic maps of cells in diverse TME across various disease stages, and experimentally validated the key molecules within it. Results: We delineated the heterogeneity among tumor cells, immune cells (including T cells, B cells, and myeloid cells), and stromal cells (such as fibroblasts and endothelial cells) during the tumorigenesis of HSCC. We uncovered the alterations in function and state of distinct cell clusters at different stages of tumor development and identified specific clusters closely associated with the tumorigenesis of HSCC. Consequently, we discovered molecules like MAGEA3 and MMP3, pivotal for the diagnosis and treatment of HSCC. Discussion: Our research sheds light on the dynamic alterations within the TME during the tumorigenesis of HSCC, which will help to understand its mechanism of canceration, identify early diagnostic markers, and discover new therapeutic targets.

Hadamard ghost imaging with a small amount of mask plates based on a spread spectrum.

Ghost imaging techniques using low-cost bucket detectors have unrivaled advantages for some wavebands where plane array detectors are not available or where focusing is difficult. In these bands, fine mask plates are the key to implementing high-resolution and quality ghost imaging. However, manufacturing a large number of mask plates is necessary but undoubtedly expensive in traditional Hadamard ghost imaging (HGI). Inspired by the spread spectrum technology, Hadamard ghost imaging based on spread spectrum (HGI-SS) is proposed, in which only two sets of a small number of mask plates are needed to accomplish Nyquist sampling for the object. Their numbers are equal to the lateral pixel resolution and the vertical pixel resolution of the object, respectively. Optical experiments verify the effectiveness of the scheme. For ghost imaging with a resolution requirement of 128 × 128 pixels, HGI-SS needs to prepare only 256 mask plates, while the traditional HGI needs to prepare 16,384 mask plates. HGI-SS may be helpful to expand the pixel resolution of imaging at a relatively low cost of mask plates.

Can a "Pandemic Life Adaptation" Digital Technology Curriculum Reduce the Digital Disadvantage of Older Adults During COVID-19? An Intervention Study from Shanghai.

Older adults are at a digital disadvantage because of social stereotypes and a lack of social support; however, smartphones have become a necessary technology to cope with crises and daily life in China, especially during the pandemic. This study aimed to help marginalized older adults take on new tasks by developing digital technology education that used a framework of social cognitive theory in social work. The study followed a quasi-experimental design in which 153 elderly people were recruited from three community service centers; 90 of the participants received 6-weekly intervention. Intent-to-treat analysis, effect size calculations, and sensitivity analysis were conducted. The findings show that digital education significantly enhanced two domains of digital life adaptation abilities: general digital life adaptation abilities [g = .50, 95% CI (.70, 2.69)] and pandemic digital life adaptation abilities [g = .89, 95% CI (.96, 2.07)]. The intervention also improved three domains of digital self-efficacy: sharing and communication [g = .55, 95% CI (.04, .48)], verification [g = .34, 95% CI (.01, .59)], and influencing others [g = .53, 95% CI (.13, .77)]. The study showed that the new intervention approach reduced the harm to vulnerable older adults in the digital wave, especially during the pandemic.

Rapid detection of furanyl fentanyl in complex matrices using Leidenfrost desorption-assisted low-temperature arc plasma ionization mass spectrometry.

The abuse of illicit drugs poses serious threats to the physical and mental health of users, as well as to the overall safety and welfare of society. In this work, we present a newly developed technique for drug detection based on mass spectrometry. This technique combines Leidenfrost desorption with low-temperature arc plasma ionization mass spectrometry. This method is applicable for detecting furanyl fentanyl in complex matrices. Key advantages of this technique include minimal sample fragmentation and high sensitivity for detection. The Leidenfrost desorption plays a pivotal role in this methodology, as it spontaneously concentrates analyte molecules during the gradual evaporation of the solvent. Eventually, these concentrated molecules are redistributed at their highest concentrations, resulting in exceptionally high sensitivity. In the course of our investigation, we achieved a remarkable detection limit of 10 pg mL-1 for furanyl fentanyl in pure water. Moreover, the characteristic ion peaks of furanyl fentanyl can be distinctly identified within complex matrices such as wine, beverages, urine, and lake water. This innovative drug detection technology offers several advantages, including a simple setup, cost-effectiveness, rapid detection, high sensitivity, and minimal sample pretreatment.

Effects of Levosimendan on Diaphragmatic Dysfunction in Patients with Sepsis.

OBJECTIVE: In this study, our aim was to examine the effects of levosimendan on diaphragmatic dysfunction in patients with sepsis, as well as assess its impact on respiratory muscle contractility and the outcome of weaning. METHODS: This was a single-blind, randomized, controlled trial. Patients with diaphragmatic dysfunction and failure of spontaneous breathing trials (SBT) were randomly and equally assigned to the experimental and control groups. The experimental group received levosimendan at a loading dose of 6 µg/kg for 10 minutes, followed by a continuous infusion at 0.2 µg/kg/min. The control group received an equivalent dose of a placebo. The pre- and post-administration respiratory mechanics parameters of the patients were recorded. Evaluation of the effect of levosimendan on patients with sepsis-induced diaphragm dysfunction comprised arterial blood gas analysis as well as ultrasound measurements of diaphragm excursion (DE), diaphragm thickness (DT), diaphragm thickening fraction (TFdi), and diaphragm-rapid shallow breathing index (D-RSBI). RESULTS: Forty-four patients were enrolled in the study. We found that post-administration of levosimendan, the patients' tidal volume (GCSMV) increased, while the D-RSBI decreased, and the partial pressure of carbon dioxide (PACO 2 ) decreased when compared to the pre-administration levels. Additionally, following levosimendan administration, patients showed increased DE and pressure support (PS) when compared to before administration (1.14 ± 0.177 vs. 1.22 ± 0.170 cm and 0.248 ± 0.03 vs. 0.284 ± 0.06, respectively), and decreased D-RSBI (22.76 ± 6.14 vs. 20.06 ± 6.04, respectively), all of which were statistically significant ( P < 0.05). In contrast, in the control group of patients, there were no statistically significant differences in the post-administration levels of DE, TFdi, and D-RSBI as compared to the pre-administration period ( P > 0.05). Furthermore, in terms of weaning outcomes, we did not find any statistically significant difference in the number of patients in the two groups who eventually underwent weaning ( P = 0.545). CONCLUSION: In this study, we found that levosimendan enhanced diaphragm contractile function. However, further investigations are required to explore its effect on weaning outcomes in patients undergoing mechanical ventilation.

Tensor-Free Holographic Metasurface Leaky-Wave Multi-Beam Antennas with Tailorable Gain and Polarization.

Recently, the community has seen a rise in interest and development regarding holographic antennas. The planar hologram is made of subwavelength metal patches printed on a grounded dielectric board, constituting flat metasurfaces. When a known reference wave is launched, the hologram produces a pencil beam towards a prescribed direction. Most earlier works on such antennas have considered only a single beam. For the few later ones that studied multiple beams, they were achieved either by having each beam taken care of by a distinct frequency or by partitioning the hologram, thereby depriving each beam of the directivity it could have had it not shared the holographic aperture with other beams. There have been recent studies related to the use of tensor surface impedance concepts for the synthesis of holograms which have attained control over the polarizations and intensities of the beams. However, this approach is complicated, tedious, and time-consuming. In this paper, we present a method for designing a planar holographic leaky-wave multi-beam metasurface antenna, of which each simultaneous beam radiating at the same frequency towards any designated direction has a tailorable amplitude, phase, and polarization, all without hologram partitioning. Most importantly, this antenna is exempted from the need for the cumbersome technique of tensor impedance. Such features of beam configurability are useful in selective multiple-target applications that require differential gain and polarization control among the various beams. Only a single source is needed, which is another benefit. In addition, effective methods to mitigate sidelobes are also proposed here. Designs by simulations according to the method are herein validated with measurements performed on fabricated prototypes.

New indolequinazoline alkaloids from the fruits of Tetradium ruticarpum.

In this research, five new indolequinazoline alkaloids (1-5), along with six known indolequinazoline alkaloids (6-11) were obtained from the fruits of Tetradium ruticarpum. Their structures were elucidated through comprehensive spectroscopic data of 1D and 2D NMR, HRESIMS and ECD spectra. Additionally, all isolates were assayed for their SIRT1 inhibitory activities in vitro and compounds 2, 7, 10 and 11 exhibited activities with IC50 values ranged from 43.16 to 118.35 µM.

Tissue-Resident Alveolar Macrophages Reduce Ozone-induced Inflammation via MerTK-mediated Efferocytosis.

Lung inflammation, caused by acute exposure to ozone (O3), one of the six criteria air pollutants, is a significant source of morbidity in susceptible individuals. Alveolar macrophages (AMØs) are the most abundant immune cells in the normal lung, and their number increases after O3 exposure. However, the role of AMØs in promoting or limiting O3-induced lung inflammation has not been clearly defined. In this study, we used a mouse model of acute O3 exposure, lineage tracing, genetic knockouts, and data from O3-exposed human volunteers to define the role and ontogeny of AMØs during acute O3 exposure. Lineage-tracing experiments showed that 12, 24, and 72 hours after exposure to O3 (2 ppm) for 3 hours, all AMØs were of tissue-resident origin. Similarly, in humans exposed to filtered air and O3 (200 ppb) for 135 minutes, we did not observe at ∼21 hours postexposure an increase in monocyte-derived AMØs by flow cytometry. Highlighting a role for tissue-resident AMØs, we demonstrate that depletion of tissue-resident AMØs with clodronate-loaded liposomes led to persistence of neutrophils in the alveolar space after O3 exposure, suggesting that impaired neutrophil clearance (i.e., efferocytosis) leads to prolonged lung inflammation. Moreover, depletion of tissue-resident AMØs demonstrated reduced clearance of intratracheally instilled apoptotic Jurkat cells, consistent with reduced efferocytosis. Genetic ablation of MerTK (MER proto-oncogene, tyrosine kinase), a key receptor involved in efferocytosis, also resulted in impaired clearance of apoptotic neutrophils after O3 exposure. Overall, these findings underscore the pivotal role of tissue-resident AMØs in resolving O3-induced inflammation via MerTK-mediated efferocytosis.

Withanolides from Physalis angulata var. villosa and the Relative Configurational Revision of Some Known Analogs.

Physalis angulata var. villosa is a plant possessing abundant withanolides, but in-depth research is lacking. In our ongoing study of P. angulata var. villosa, 15 previously undescribed withanolides (1-15), along with 21 known analogs (16-36), were isolated from the whole plant. The structures of the withanolides (1-15) were elucidated based on analysis of their 1D and 2D NMR, HRESIMS, and ECD data. Additionally, the application of γ-gauche effects with the help of ROESY correlations led to the formulation of empirical rules for withanolides with 14-OH/15-OAc to rapidly determine the 14-OH orientations, making it possible to propose configurational revisions of 19 previously reported analogs (1'-19'). Withanolides 1, 4-6, and 10 showed potent cytotoxic activities against three human cancer cell lines (HCT-116, MDA-MB-231, and A549).

Prediction of fluid responsiveness for patients in shock using a ventilator disconnection test combined with the pulse contour-derived cardiac index.

BACKGROUND: Finding a simple and reliable method to predict and assess fluid responsiveness has long been of clinical interest. OBJECTIVE: To investigate the predictive value of a ventilator disconnection (DV) test combined with the pulse contour-derived cardiac output (PiCCO) index on fluid responsiveness for patients in shock. METHODS: Thirty-two patients were chosen for the study. Patients who were in shock, received mechanical ventilation, and met the inclusion criteria were selected. Patients were divided into a fluid-responsive group (14 patients) and fluid-unresponsive group (18 patients) based on whether the increase in cardiac index (Δ CI) was > 10% or not, respectively, following the fluid challenge test. Changes in heart rate, pulse oximeter-measured oxygen saturation, mean arterial pressure (MAP), and CI before and after passive leg raising (PLR), DV, and fluid challenge tests were observed. We used Pearson's correlation coefficient to analyze an increase in the MAP (Δ MAP) and Δ CI before and after the PLR, DV, and fluid challenge tests; the sensitivity and specificity of the Δ MAP and Δ CI in the PLR and DV tests for predicting fluid response were also analyzed by plotting the receiver operating characteristic (ROC) curves. RESULTS: CI results in the PLR and DV tests, as well as the fluid challenge test, were significantly higher in the fluid-responsive group compared with before the test (P< 0.05). The Δ CI before and after the PLR, DV, and fluid challenge tests were positively correlated among patients in the fluid-responsive group. The area under the ROC curve for the post-PLR test CI and the post-DV CI for predicting fluid responsiveness was 0.869 (95% confidence interval (CI) [0.735-1.000, P= 0.000]) and 0.937 (95% CI [0.829-1.000, P= 0.000]), respectively, in patients in the fluid-responsive group. The sensitivity and specificity of the post-DV CI for predicting fluid responsiveness in all patients was 100.0% and 88.9%, respectively, using a 5% increase as the cut-off value. CONCLUSION: Application of DV, combined with PiCCO, has a high predictive value for fluid responsiveness among patients in shock.

Nurses' Work-Family Strategies during COVID-19 Lockdown and Their Association with Individual Health and Family Relations.

The COVID-19 lockdown forced people to stay at home and address their family duties more equally. However, since nurses themselves were involved in the closed-loop management in hospitals and unable to return home, there was also an increased likelihood of non-traditional work-family strategies emerging. To ascertain the extant and implications of this phenomenon, this cross-sectional study explores work-family management strategies among nurses during the COVID-19 lockdown and their association with nurses' individual health, family relationships, and job performance. Survey data were collected from 287 nurses who were involved in the closed-loop management in Shanghai hospitals from March to June 2022. Latent Class Analysis of seven categorical variables of nurses' work-family status (e.g., the division of childcare labor) produced a best-fit solution of five strategies (BLRT (p) < 0.001, LMR (p) = 0.79, AIC = 5611.34, BIC = 6302.39, SSA-BIC = 5703.65, Entropy = 0.938): (1) fully outsourcing to grandparents, (2) partially outsourcing to grandparents, with the husband filling in the gap, (3) the husband does it all, (4) egalitarian remote workers, and (5) a neo-traditional strategy. Nurses who applied the egalitarian strategy had less psychological distress and relationship tension and better performance than those who applied the neo-traditional strategy and performed most of the childcare. The "husband does it all" strategy and the outsourcing strategies seem to have double-edged effects, with better job performance and family relations but also more distress and fewer sleeping hours among nurses. Overall, with a view to future risk mitigation, policymakers and practitioners should be aware of the diversity of the work-family strategies among nurse families during the lockdown period, and their association with individual and family outcomes, and provide tailored support.

Optical authentication method based on correspondence ghost imaging.

Ghost imaging technology has a great application potential in optical security because of its non-local characteristics. In this paper, on the basis of computational ghost imaging, an optical authentication scheme is proposed that utilizes the correspondence imaging technique for the preliminary reconstruction of the object image, and then authenticates the image by a nonlinear correlation algorithm. Different from the previous optical authentication schemes that usually adopted random selection of measurements, this authentication method consciously selects the bucket detector measurement values with large fluctuation and can achieve authentication using ultra-low data volumes less than 1% of the Nyquist limit. In brief, this scheme is easy to implement and has a simpler algorithm and higher stability, which is a tremendous advantage in practical optical authentication systems. The simulation and physical experimental results demonstrate the feasibility of the scheme.

MSA-GCN: A Multi-information Selection Aggregation Graph Convolutional Network for Breast Tumor Grading.

Physicians typically combine multi-modal data to make a graded diagnosis of breast tumors. However, most existing breast tumor grading methods rely solely on image information, resulting in limited accuracy in grading. This paper proposes a Multi-information Selection Aggregation Graph Convolutional Networks (MSA-GCN) for breast tumor grading. Firstly, to fully utilize phenotypic data reflecting the clinical and pathological characteristics of tumors, an automatic combination screening and weight encoder is proposed for phenotypic data, which can construct a population graph with improved structural information. Then, a graph structure is designed through similarity learning to reflect the correlation between patient image features. Finally, a multi-information selection aggregation mechanism is employed in the graph convolution model to extract the effective features of multi-modal data and enhance the classification performance of the model. The proposed method is evaluated on different clinical datasets from the Digital Database for Screening Mammography (DDSM) and INbreast. The average classification accuracies are 90.74% and 85.35%, respectively, surpassing the performance of existing methods. In conclusion, our method effectively fuses image and non-image information, leading to a significant improvement in the accuracy of breast tumor grading.

Discovery and optimization of indirubin derivatives as novel ferroptosis inducers for the treatment of colon cancer.

Glutathione peroxidase 4 (GPX4) is an essential antioxidant enzyme that negatively regulates ferroptosis. To exploit novel GPX4 inhibitors, we designed and synthesized 32 indirubin derivatives. Compound 31 exhibited the strongest antitumor activity against HCT-116 cells (IC50 = 0.49 ± 0.02 µM). Further studies suggested that 31 could induce ferroptosis in colon cancer cells and its cytotoxic activity could be reversed by ferroptosis inhibitors. Mechanism research showed that 31 promoted the degradation of GPX4, causing the accumulation of lipid ROS to induce ferroptosis. Animal experiments also proved that 31 could inhibit the growth of colon cancer cells in vivo and reduce the expression of GPX4 in tumor tissues. These results indicated that compound 31 had potential as a novel ferroptosis inducer agent for colon cancer.

Estimation for running time and energy losses due to unproductive stops at bus stations in urban-rural traffic corridors.

To provide data support for developing fixed-route DRT based on FRT to reduce operating costs inside base routes in urban-rural traffic corridors, this paper estimated running time and energy losses due to unproductive stops at bus stations in urban-rural traffic corridors. Firstly, 14 urban-rural bus routes without ticket sellers in Xi'an are selected to demonstrate the universality of unproductive stops at bus stations. Secondly, a model for estimating running time and energy losses based on the VT-CPFM model is developed. Finally, running time and energy losses due to unproductive stops in two representative urban-rural traffic corridors are estimated. Estimated results show that the average running time loss ratios of different rounds in Routes 332, 333, 335, 338 and G1 range from 8.30% to 17.52% and that average fuel loss ratios range from 9.16% to 13.30%. In addition, the monetary loss in energy consumption of Route G1 in 2019 is estimated to be up to 193213 yuan. This study proves that unproductive stops at bus stations generally exist in urban-rural bus routes and can result in significant running time and energy losses and that developing fixed-route DRT based on FRT leveraging V2I with mobile APP in representative urban-rural traffic corridors is very necessary, which is expected to reduce energy consumption and running time.

A comparative study of the attentional blink of facial expression in deaf and hearing children.

The rapid serial visual presentation paradigm was used to investigate differences in the attentional blink between deaf children and hearing children in response to facial expressions of fear and disgust. The results showed that: (1) deaf and hearing children had a higher accuracy rate for T1 with disgustful facial expression than T1 with fear facial expression, (2) There was no significant difference in attentional blink between deaf and hearing children, (3) When T2 appeared at Lag6, the response accuracy of T2 in the disgust T1 condition was lower than that in fear T1 condition. However, no significant difference in T2 at Lag2 was found between the two conditions. The results showed that deaf children and those with hearing were more sensitive to facial expressions of disgust, which captured more attentional resources, and the ability of visual attention of deaf children was not weaker than hearing children.

The Effectiveness of Cognitive Behavioral Therapy for Depression Among Individuals with Diabetes: a Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: Depression is prevalent and common among individuals living with diabetes. The aim of this review is to systematically assess and meta-analyze the treatment effect of cognitive-behavioral therapy for depression (and other affective outcomes) among patients with diabetes. RECENT FINDINGS: Earlier investigations found both psychosocial and pharmacological interventions, including cognitive-behavioral therapy, were promising in managing depression in patients with diabetes, though these findings remain inclusive due to poor study designs and a small number of trials included, which calls for a comprehensive systematic review and meta-analysis. A total of 33 studies (89 effect sizes) reported a moderate and statistically significant treatment effect of cognitive-behavioral therapy for depressive symptoms among individuals with diabetes (d = 0.301, 95% CI 0.115-0.487, p < 0.001). On average, cognitive-behavioral therapy was effective for psychological stress/distress outcomes but not for anxiety or physiological outcomes. The findings of the study confirmed CBT as an effective treatment option for depression among diabetes patients and identified important areas for future research.

Theoretical study on the adsorption and oxidation of glucose on Au(111) surface.

CONTEXT: While Au-based catalysts recently have shown tremendous potential in glucose oxidation to gluconic acid, the detailed reaction mechanism is still unclear, which impedes the development of direct glucose fuel cell (DGFC). METHODS: Using density functional theory (DFT), we exhibit some new adsorption configurations and oxidation mechanisms by considering both the open chain form and the ring form of glucose on Au(111) surface in the presence of OH. The strong interactions between glucose and the OH adsorbed surface are obtained. Moreover, form the calculated energy pathways, the oxidation of glucose in the open chain involves the dissociation of the formyl C - H bond by the adsorbed OH, while the ring form glucose oxidation is initiated by O - H bond rupture rather than C - H bond scission and preferentially undergoes the ring-open process to generate the open chain form glucose. Meanwhile, the results demonstrate that the adsorbed OH assists in reducing the activation energy of reaction process.

Assessment of factors influencing the olfactory bulb volume in patients with post-viral olfactory dysfunction.

PURPOSE: To investigate the factors influencing the volume of the olfactory bulb (OB) in patients with post-viral olfactory dysfunction (PVOD). METHODS: We collected 92 olfactory bulb volumes from patients with PVOD who underwent a sinus computed tomographic and magnetic resonance imaging (MRI) scan of the head and collected clinical information including gender, age, disease course, minimal cross-sectional area, nasal airway resistance, and olfactory function. OB volume was measured in MRI and the scans were evaluated according to the Lund-Mackay (LM) scoring system. RESULTS: Male patients with PVOD had a larger OB volume (ß = 0.284, P < 0.05). OB volume was smaller in patients with a longer course of olfactory dysfunction (ß = - 0.254, P < 0.05). According to the LM scoring system, patients with a higher anterior ethmoidal sinus score had smaller OB volume (ß = - 0.476, P < 0.05). CONCLUSIONS: The study revealed that gender, disease course, and the score of anterior ethmoidal sinusitis can affect the OB volume in patients with PVOD.

Broadband Near-Infrared Luminescence in Garnet Y3Ga3MgSiO12: Cr3+ Phosphors.

Broadband near-infrared (NIR) phosphors are the critical component of phosphor converted NIR light-emitting diode (LED) light sources. However, there are still a lack of NIR phosphors with excellent external quantum efficiency (EQE) and thermal stability. Here, we report a highly efficient broadband NIR phosphor Y3Ga3MgSiO12: Cr3+. The optimized phosphor yields an internal quantum efficiency (IQE) and an EQE of 79.9 and 33.7%, respectively. The integrated emission intensity still remains at 84.4% of that at room temperature when heated to 423 K. A broadband NIR LED lamp was made by combining as-prepared phosphor and a blue InGaN LED chip, which shows an output power of 89.8 mW with a photoelectric conversion efficiency of 17.1% driven at 525 mW input power. Our research provides a promising NIR phosphor with high efficiency broadband for the NIR light source.