Profibrotic monocyte-derived alveolar macrophages are expanded in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19.

Monocyte-derived alveolar macrophages drive lung injury and fibrosis in murine models and are associated with pulmonary fibrosis in humans. Monocyte-derived alveolar macrophages have been suggested to develop a phenotype that promotes lung repair as injury resolves. We compared single-cell and cytokine profiling of the alveolar space in a cohort of 35 patients with post-acute sequelae of COVID-19 who had persistent respiratory symptoms and abnormalities on a computed tomography scan of the chest that subsequently improved or progressed. The abundance of monocyte-derived alveolar macrophages, their gene expression programs, and the level of the monocyte chemokine CCL2 in bronchoalveolar lavage fluid positively associated with the severity of radiographic fibrosis. Monocyte-derived alveolar macrophages from patients with resolving or progressive fibrosis expressed the same set of profibrotic genes. Our findings argue against a distinct reparative phenotype in monocyte-derived alveolar macrophages, highlighting their utility as a biomarker of failed lung repair and a potential target for therapy.

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.

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.

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.

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).

Discovery of piperine derivatives as inhibitors of human dihydroorotate dehydrogenase to induce ferroptosis in cancer cells.

Inhibition of human dihydroorotate dehydrogenase (hDHODH) represents a promising strategy for suppressing the proliferation of cancer cells. To identify novel and potent hDHODH inhibitors, a total of 28 piperine derivatives were designed and synthesized. Their cytotoxicities against three human cancer cell lines (NCI-H226, HCT-116, and MDA-MB-231) and hDHODH inhibitory activities were also evaluated. Among them, compound H19, exhibited the strongest inhibitory activities (NCI-H226 IC50 = 0.95 µM, hDHODH IC50 = 0.21 µM). Further pharmacological investigations revealed that H19 exerted anticancer effects by inducing ferroptosis in NCI-H226 cells, with its cytotoxicity being reversed by ferroptosis inhibitors. This was supported by the intracellular growth or decline of ferroptosis markers, including lipid peroxidation, Fe2+, GSH, and 4-HNE. Overall, H19 emerges as a promising hDHODH inhibitor with potential anticancer properties warranting development.

Prognostic value of the postoperative carcinoembryonic antigen level in colorectal cancer: A meta-analysis.

BACKGROUND: Carcinoembryonic antigen (CEA) is one of the commonly used preoperative biomarkers for colorectal cancer (CRC), but no meta-analysis has evaluated the findings of all recently published studies to determine whether its postoperative level can serve as a prognostic indicator. METHODS: We conducted a systematic search for eligible literature from the PubMed, EMBASE, and Web of Science databases in October 2023. Studies that investigated the relationship between postoperative serum CEA levels and prognosis in CRC patients were included. Outcome indicators, including overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS)/recurrence-free survival (RFS), were analyzed using a fixed-effects or random-effects model. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used as effective values. RESULTS: This meta-analysis included 20 eligible studies involving 10,114 CRC patients from the East Asian and Western countries. A comprehensive analysis revealed that elevated postoperative CEA levels were associated with low OS (HR: 2.92, 95% CI: 2.36-3.62, and p < 0.000), DFS (HR: 2.81, 95% CI: 2.01-3.94, and p < 0.000), and RFS/PFS (HR: 2.52, 95% CI: 1.75-3.62, p < 0.000). A subgroup analysis by region, analysis type, distant metastasis, HR obtain method, sample size, postoperative measurement date, and study design demonstrated that the negative correlation observed between high serum CEA levels after surgery and poor prognosis was not significantly different between the subgroups. CONCLUSION: When CEA levels are found to be elevated during postoperative follow-up, more active intervention measures should be implemented to further improve the patient's survival outcomes.

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.

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.

Carbon ion radiotherapy with pencil beam scanning for hepatocellular carcinoma: Long-term outcomes from a phase I trial.

This study evaluates the feasibility of the pencil beam scanning technique of carbon ion radiotherapy (CIRT) in the setting of hepatocellular carcinoma (HCC) and establishes the maximum tolerated dose (MTD) calculated by the Local Effect Model version I (LEM-I) with a dose escalation plan. The escalated relative biological effectiveness-weighted dose levels included 55, 60, 65, and 70 Gy in 10 fractions. Active motion management techniques were employed, and several measures were applied to mitigate the interplay effect induced by a moving target. CIRT was planned with the LEM-I-based treatment planning system and delivered by raster scanning. Offline PET/CT imaging was used to verify the beam range. Offline adaptive replanning was performed whenever required. Twenty-three patients with a median tumor size of 4.3 cm (range, 1.7-8.5 cm) were enrolled in the present study. The median follow-up time was 56.1 months (range, 5.7-74.4 months). No dose limiting toxicity was observed until 70 Gy, and MTD had not been reached. No patients experienced radiation-induced liver disease within 6 months after the completion of CIRT. The overall survival rates at 1, 3, and 5 years were 91.3%, 81.9%, and 67.1% after CIRT, respectively. The local progression-free survival and progression-free survival rates at 1, 3 and 5 years were 100%, 94.4%, and 94.4% and 73.6%, 59.2%, and 37.0%, respectively. The raster scanning technique could be used to treat HCC. However, caution should be exercised to mitigate the interplay effect. CIRT up to 70 Gy in 10 fractions over 2 weeks was safe and effective for HCC.

Bipolar compressive ghost imaging method to improve imaging quality.

Compressive ghost imaging (CGI) can effectively reduce the number of measurements required for ghost imaging reconstruction. In most cases, however, when using illumination patterns as measurement matrices, CGI has not demonstrated the ability to reconstruct high-quality images at an ultra-low sampling rate as perfect as claimed by compressive sensing theory. According to our analysis, the reason is that the non-negative nature of light intensity causes measurement matrix in compressive ghost imaging to be inconsistent with the essential requirements of good measurement matrix in compressive sensing theory, leading to low reconstruction quality. Aiming at this point, we propose a bipolar compressive ghost imaging method to improve the reconstruction quality of ghost imaging. The validity of the proposed method is proven by simulations and experiments.

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.

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.

Novel NQO1 substrates bearing two nitrogen redox centers: Design, synthesis, molecular dynamics simulations, and antitumor evaluation.

By analyzing the crystal structure of NQO1, an additional binding region for the ligand was discovered. In this study, a series of derivatives with a novel skeleton bearing two nitrogen redox centers were designed by introducing amines or hydrazines to fit with the novel binding region of NQO1. Compound 24 with a (4-fluorophenyl)hydrazine substituent was identified as the most efficient substrate for NQO1 with the reduction rate and catalytic efficiency of 1972 ± 82 µmol NADPH/min/µmol NQO1 and 6.4 ± 0.4 × 106 M-1s-1, respectively. Molecular dynamics (MD) simulation revealed that the distances between the nitrogen atom of the redox centers and the key Tyr128 and Tyr126 residues were 3.5 Å (N1-Tyr128) and 3.4 Å (N2-Tyr126), respectively. Compound 24 (IC50/A549 = 0.69 ± 0.09 µM) showed potent antitumor activity against A549 cells both in vitro and in vivo through ROS generation via NQO1-mediated redox cycling, leading to a promising NQO1-targeting antitumor candidate.

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.

Efficacy of Levosimendan in the Treatment of Patients With Severe Septic Cardiomyopathy.

OBJECTIVE: This study was designed to compare the effects of levosimendan and dobutamine on hemodynamics and clinical efficacy in patients with severe septic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤35%). DESIGN: A prospective, single-blind, randomized controlled study. SETTING: In Baoding, China. PARTICIPANTS: Thirty patients with severe septic cardiomyopathy treated in the authors' hospital's Department of Critical Medicine from September 2018 to September 2021 were enrolled in this study. INTERVENTIONS: These patients were divided randomly into the levosimendan group and dobutamine group. The LVEF, cardiac index (CI), stroke volume index (SVI), systemic vascular resistance index, heart rate, norepinephrine dose, and lactate at the time of enrollment and the 24th hour were compared, along with myocardial injury markers on the third day, C-reactive protein, mechanical ventilation time, length of intensive care unit (ICU) stay, cost, and 28-day mortality. The primary outcome was 28-day mortality. MEASUREMENTS AND MAIN RESULTS: At the 24th hour after treatment, CI, LVEF, SVI, and fluid volume were found to be higher in the levosimendan group than in the dobutamine group, whereas the dose of norepinephrine was lower in the former rather than the latter group. On the third day of treatment, cardiac troponin I in the levosimendan group was lower than that in the dobutamine group. Although the differences in 28-day mortality, ICU stay, and ICU treatment cost between the groups were not statistically significant, the ventilator application time of the levosimendan group was significantly shorter than that of the dobutamine group. CONCLUSIONS: Compared with dobutamine, levosimendan was more effective at improving cardiac function, reducing myocardial injury, and reducing mechanical ventilation time in patients with severe septic cardiomyopathy.

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.

Withanolides from Physalin angulata and Their Inhibitory Effects on Nitric Oxide Production.

Six new withanolides, angulasteroidins A-F (1-6), along with twelve known analogs (7-18) were isolated from the whole plants of Physalis angulata. Their structures were elucidated by analysis of 1D and 2D NMR, ECD and IR spectra, HR-ESI-MS data, and ECD calculation. Compounds 1 and 6 were rare 1-10 seco withanolides. Compounds 2-4, 7-9, and 15 exhibited significant inhibitory activity on the production of nitric oxide in the LPS-activated RAW 264.7 mouse macrophage cell lines with IC50 values ranging from 0.23 to 9.06 µM.

A Study on the Interactions of Proteinase K with Myricetin and Myricitrin by Multi-Spectroscopy and Molecular Modeling.

Myricetin (MYR) and myricitrin (MYT) are well recognized for their nutraceutical value, such as antioxidant, hypoglycemic, and hypotensive effects. In this work, fluorescence spectroscopy and molecular modeling were adopted to investigate the conformational and stability changes of proteinase K (PK) in the presence of MYR and MYT. The experimental results showed that both MYR and MYT could quench fluorescence emission via a static quenching mechanism. Further investigation demonstrated that both hydrogen bonding and van der Waals forces play significant roles in the binding of complexes, which is consistent with the conclusions of molecular modeling. Synchronous fluorescence spectroscopy, Förster resonance energy transfer, and site-tagged competition experiments were performed to prove that the binding of MYR or MYT to PK could alter its micro-environment and conformation. Molecular docking results revealed that either MYR or MYT spontaneously interacted with PK at a single binding site via hydrogen bonding and hydrophobic interactions, which is consistent with the results of spectroscopic measurements. A 30 ns molecular dynamics simulation was conducted for both PK-MYR and PK-MYT complexes. The calculation results showed that no large structural distortions or interaction changes occurred during the entire simulation time span. The average RMSD changes of PK in PK-MYR and PK-MYT were 2.06 and 2.15 Å, respectively, indicating excellent stability of both complexes. The molecular simulation results suggested that both MYR and MYT could interact with PK spontaneously, which is in agreement with spectroscopic results. This agreement between experimental and theoretical results indicates that the method herein could be feasible and worthwhile for protein-ligand complex studies.

[Application of artificial intelligence in the diagnosis of prostate cancer].

With the rise of precision medicine, the continuous expansionWith the rise of precision medicine, the continuous expansion the collective push from many other the application of Artificial Intelligence (AI) in prostate cancer diagnosis is increasingly becoming a focal point. AI technology can effectively utilize diverse detection methods such as Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), and whole pathology slide imaging to efficiently identify and differentiate between benign and malignant lesions. The encouraging results from numerous studies herald the enormous potential of this field. This article aims to provide a comprehensive summary and analysis of the research progress made in AI for prostate cancer diagnosis, in order to better grasp the trends in this area of development.