N6-methyladenosine reader protein IGF2BP1 suppresses CD8 + T cells-mediated tumor cytotoxicity and apoptosis in colon cancer.

Tumor immune escape is an important manner for colon cancer to escape effective killing by immune system. Currently, the immune checkpoint PD-1/PD-L1-targeted immunotherapy has emerged as a promising therapeutic strategy in colon cancer. Here, present work aims to investigate the biological function of N6-methyladenosine (m6A) reader insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) in regulating colon cancer's immune escape and CD8 + T cells-mediated tumor cytotoxicity and apoptosis. Results illustrated that IGF2BP1 was closely correlated to the colon cancer patients' poor clinical outcome. Functionally, upregulation of IGF2BP1 suppressed the CD8+ T-cells mediated antitumor immunity through reducing their tumor cytotoxicity. Mechanistically, MeRIP-Seq revealed that programmed death ligand 1 (PD-L1) mRNA had a remarkable m6A modified site on 3'-UTR genomic. Moreover, PD-L1 acted as the target of IGF2BP1, which enhanced the stability of PD-L1 mRNA. Overall, these results indicated that IGF2BP1 targeted PD-L1 to accelerate the immune escape in colon cancer by reducing CD8 + T cells-mediated tumor cytotoxicity in m6A-dependent manner. The findings demonstrate the potential of m6A-targeted immune checkpoint blockade in colon cancer, providing a novel insight for colon cancer immune escape and antitumor immunity in further precise treatment.

Single-double-band switchable optical circular polarizers based on surface plasmon resonance.

A single-double-band switchable circular polarization filter based on surface plasmon resonance exhibits significant potential for applications in fields such as communication and sensing due to its adjustable, low-cost, and easy integration features. In this study, we propose a bi-layer rod nanostructure and use FEM simulation to study the transmission spectra of the structure. The results demonstrate that the structure exhibits both single- and double-band circular polarization filtering effects, which can be switched by varying geometric parameters such as the distance between the two layers and the width of nanorods. Furthermore, the filtering effects of both single- and double-band are highly dependent on the length of the nanorods, with average extinction rates reaching 486 and 2020/129, respectively; the operating bandwidths (defined as extinction ratio >10) can reach 170 nm and 35 nm/70 nm, respectively. The underlying physical mechanisms are clarified by analyzing the electric dipole, magnetic dipole resonance modes, and induced chiral fields on nanostructures.

Single-double-band switchable optical circular polarizers based on surface plasmon resonance: publisher's note.

This publisher's note reports a correction in Appl. Opt.63, 1153 (2024)APOPAI0003-693510.1364/AO.513837.

Development and validation of a risk prediction model for community-acquired pressure injury in a cancer population: A case-control study.

BACKGROUND: Patients with cancer are susceptible to pressure injuries, which accelerate deterioration and death. In patients with post-acute cancer, the risk of pressure injury is ignored in home or community settings. OBJECTIVE: To develop and validate a community-acquired pressure injury risk prediction model for cancer patients. METHODS: All research data were extracted from the hospital's electronic medical record system. The identification of optimal predictors is based on least absolute shrinkage and selection operator regression analysis combined with clinical judgment. The performance of the model was evaluated by drawing a receiver operating characteristic curve and calculating the area under the curve (AUC), calibration analysis and decision curve analysis. The model was used for internal and external validation, and was presented as a nomogram. RESULTS: In total, 6257 participants were recruited for this study. Age, malnutrition, chronic respiratory failure, body mass index, and activities of daily living scores were identified as the final predictors. The AUC of the model in the training and validation set was 0.87 (95 % confidence interval [CI], 0.85-0.89), 0.88 (95 % CI, 0.85-0.91), respectively. The model demonstrated acceptable calibration and clinical benefits. CONCLUSIONS: Comorbidities in patients with cancer are closely related to the etiology of pressure injury, and can be used to predict the risk of pressure injury. IMPLICATIONS FOR PRACTICE: This study provides a tool to predict the risk of pressure injury for cancer patients. This suggests that improving the respiratory function and nutritional status of cancer patients may reduce the risk of community-acquired pressure injury.

Structural and functional characterization of novel F7 mutations identified in Chinese factor VII-deficient patients.

Hereditary factor VII (FVII) deficiency is a rare recessive bleeding disorder with an estimated prevalence of 1/500 000. We had investigated 50 unrelated Chinese patients with FVII deficiency and identified, in total, 25 mutations, including 18 missense mutations and 5 splicing mutations, on the F7 gene. The nucleotide transition c.1224T>G (p.His408Gln) in exon 9 constitutes a hotspot of mutation, with 19 patients harbouring this genetic variance. Few patients were homozygous or compound heterozygous for deleterious mutations, such as non-sense mutations, large insertion or deletions, indicating that complete deficiency of FVII may not be compatible with life. The eight novel mutations identified in the study, including one small deletion (p.Glu49GlyfsTer101), three type I missense mutations, p.Cys238Phe, p.Gly420Asp, p.Ala252Val and four type II missense mutations, p.Val336Met, p.Ser342Gly, p.Gly432Ser and p.Ile213Asn, were further analysed by in vitro expression and functional studies. The laboratory phenotype and structural analysis confirmed the functional consequence of p.Ile213Asn mutation involving cleavage and activation site. The molecular dynamic simulations and binding energy calculations along with functional probing of p.Gly432Ser mutation revealed the critical role of residue Gly432 in the binding between activated factor VII (factor VIIa) and tissue factor.

Differential susceptibility to SARS-CoV-2 in the normal nasal mucosa and in chronic sinusitis.

Human nasal mucosa is susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and serves as a reservoir for viral replication before spreading to other organs (e.g. the lung and brain) and transmission to other individuals. Chronic rhinosinusitis (CRS) is a common respiratory tract disease and there is evidence suggesting that susceptibility to SARS-CoV-2 infection differs between the two known subtypes, eosinophilic CRS and non-ECRS (NECRS). However, the mechanism of SARS-CoV-2 infection in the human nasal mucosa and its association with CRS has not been experimentally validated. In this study, we investigated whether the human nasal mucosa is susceptible to SARS-CoV-2 infection and how different endotypes of CRS impact on viral infection and progression. Primary human nasal mucosa tissue culture revealed highly efficient SARS-CoV-2 viral infection and production, with particularly high susceptibility in the NECRS group. The gene expression differences suggested that human nasal mucosa is highly susceptible to SARS-CoV-2 infection, presumably due to an increase in ACE2-expressing cells and a deficiency in antiviral immune response, especially for NECRS. Importantly, patients with NECRS may be at a particularly high risk of viral infection and transmission, and therefore, close monitoring should be considered.

Programmable focused laser differential interferometer with a spatial light modulator as a dynamic diffractive optical element.

A spatial light modulator (SLM) is incorporated into a focused laser differential interferometer (FLDI) to generate a nonlinear array of beams, and this setup is used to measure the power spectral density of a Mach-1.5, underexpanded jet of air. The results are compared with measurements from a 1-point FLDI to assess the feasibility of using SLMs in FLDI to serve as dynamic diffractive elements for generating beam arrays of any shape. The spectra comparison illustrates that spatial light modulated-FLDI (SLM-FLDI) detects similar spectral profiles to that of 1-point FLDI, especially dominant frequencies in the jet. SLM-FLDI could provide a useful expansion of FLDI capabilities.

Association between polymorphisms in connexin 40 gene (Cx40) and risk of atrial fibrillation: a meta-analysis based on 3,452 subjects.

INTRODUCTION: Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with heart failure and stroke, leading sometimes to death. But the pathogenesis of AF remains unclear. Numerous studies have investigated whether the connexin 40 (Cx40) polymorphisms influences the risk of AF, but the results are controversial. METHODS: We searched English and Chinese databases and calculated the odds ratio (OR) and 95% confidence interval (CI) to examine the existence of genetic associations between the Cx40 polymorphisms and the risk of AF. All relevant studies were screened and meta-analyzed using Review Manager 5.0. RESULTS: A total of 12 studies, including 10 studies for -44 polymorphism (rs35594137) and 4 studies for -26 polymorphism (rs10465885), were identified for the meta-analysis. For -44 polymorphism, the results showed a significantly increased risk of AF in the five genetic models in the overall analysis. Furthermore, in subgroup analysis, increased AF risks were also observed in Asian and non-Asian populations. For -26 polymorphism, the overall OR revealed an increased risk of AF in dominant model. In subgroup analysis, increased AF risk was only found in recessive genetic model of the Asian population. CONCLUSIONS: The Cx40 polymorphisms were positively associated with AF in both populations, especially on -44 polymorphism.

Clinical characteristics of adult inpatients with Measles in Beijing from 2010 to 2021: a retrospective analysis.

BACKGROUND: With the measles vaccine coverage rate gradually increasing, adult patients' epidemiological and clinical characteristics have changed. AIMS: To analyze the clinical characteristics of adult measles patients in Beijing Youan Hospital. METHODS: We retrospectively reviewed the electronic medical records of 818 patients diagnosed with measles at Beijing Youan Hospital between June 2010 and October 2021. We divided all hospitalized patients into two demographics groups, using 14 years of age as the cut-off. RESULTS: Of the adult inpatients, 110 (74.83%) were aged 20-40. There was an overall peak incidence in 2014, and yearly peaks came in April. Fever, cough, erythema, and Koplik's spots were present in 79.59%, 82.1%, 99.3%, and 59.8% of the adult group, respectively, compared to 75.26%, 92.0%, 99.9%, and 39.0% of the pediatric group. Decreased lymphocytes and hepatic impairment were common in adults. The adult group's median level of C-reactive protein was higher than that of the pediatric group (p < 0.05). The positive rate of measles antibody (IgM) detection was 64.6% in the adults and 78.8% in the pediatric group (p < 0.05). Of the adults, 46.9%, 8.8%, and 66% had pneumonia, gastroenteritis, and antibiotic use, compared to 89.6%, 2.7%, and 83.2% of the pediatric patients. The duration of symptoms before admission and the average length of hospital stay was approximately six days in both groups. CONCLUSIONS: Koplik's spots are more likely to be detected by clinicians in adult patients admitted to the hospital. Active surveillance is helpful for adults who are negative for IgM on admission. Although the proportion of adult measles patients with liver injury is high, the disease is generally mild. Measles significantly impacts peripheral blood lymphocytes in adults, but adults are at lower risk of concurrent pneumonia than the pediatric group. Clinicians need to pay attention to the appropriate use of antibiotics. Expanding the coverage of the measles vaccination in high-risk areas is beneficial for preventing measles in adults.

Discovery of endosomalytic cell-penetrating peptides based on bacterial membrane-targeting sequences.

Cell-penetrating peptides (CPPs) are prominent scaffolds for drug developments and related research, particularly the endocytic delivery of biomacromolecules. Effective cargo release from endosomes prior to lysosomal degradation is a crucial step, where the rational design and selection of CPPs remains a challenge and calls for deeper mechanistic understandings. Here, we have investigated a strategy of designing CPPs that selectively disrupt endosomal membranes based on bacterial membrane targeting sequences (MTSs). Six synthesized MTS peptides all exhibit cell-penetrating abilities, among which two d-peptides (d-EcMTS and d-TpMTS) are able to escape from endosomes and localize at ER after entering the cell. The utility of this strategy has been demonstrated by the intracellular delivery of green fluorescent protein (GFP). Together, these results suggest that the large pool of bacterial MTSs may be a rich source for the development of novel CPPs.

Peripheral immune phenotypes and T cell receptor repertoire in pneumocystis pneumonia in HIV-1 infected patients.

BACKGROUND: The host immune response to pneumocystis pneumonia (PCP) involves interactions among immune cell subsets and cytokines. However, the definite pathogenesis and immunological influences of P. jirovecii have not been fully elucidated. METHODS: Mass cytometry and high-throughput sequencing of the T cell receptor (TCR) were used to profile the host immune response to human immunodeficiency virus-1 (HIV-1) and P. jirovecii infection. RESULTS: Our findings demonstrated that patients with PCP showed different immune cell proportions when compared to healthy controls. Changes in cytokines were found after anti-PCP treatment, suggested that cytokines may play an important role in controlling the pathogen. Furthermore, PCP patients showed marked reduction of TCR repertoire diversity. The diversity of TCR repertoire was restored by the anti-PCP treatment. CONCLUSION: In summary, we profiled the composition and characteristics of immune environment in response to HIV-1 and P. jirovecii infection, which may contribute to elucidating host immunity.

One-dimensional air temperature measurements by air resonance enhanced multiphoton Ionization thermometry (ART).

In this work, a detailed calibration study is performed to establish non-intrusive one-dimensional (1D) rovibrational temperature measurements in unseeded air, based on air resonance enhanced multiphoton ionization thermometry (ART). ART is generated by REMPI (resonance enhanced multi-photon ionization) of molecular oxygen and subsequent avalanche ionization of molecular nitrogen in a single laser pulse. ART signal, the fluorescence from the first negative band of molecular nitrogen, is directly proportional to the 2-photon transition of molecular oxygen C3Π (v = 2) ← X3Σ (v'=0), which is used to determine temperature. Experimentally, hyperfine structures of the O2 rotational branches with high temperature sensitivity are selectively excited through a frequency-doubled dye laser. Electron-avalanche ionization of N2 results in the fluorescence emissions from the first negative bands of N2 + near 390, 425, and 430nm, which are captured as a 1D line by a gated intensified camera. Post processing of the N2 + fluorescence yields a 1D thermometry line that is representative of the air temperature. It is demonstrated that the technique provides ART fluorescence of ∼5cm in length in the unseeded air, presenting an attractive thermometry solution for high-speed wind tunnels and other ground test facilities.

O2 based resonantly ionized photoemission thermometry analysis of supersonic flows.

Characterization of the thermal gradients within supersonic and hypersonic flows is essential for understanding transition, turbulence, and aerodynamic heating. Developments in novel, impactful non-intrusive techniques are key for enabling flow characterizations of sufficient detail that provide experimental validation datasets for computational simulations. In this work, Resonantly Ionized Photoemission Thermometry (RIPT) signals are directly imaged using an ICCD camera to realize the techniques 1D measurement capability for the first time. The direct imaging scheme presented for oxygen-based RIPT (O2 RIPT) uses the previously established calibration data to direct excite various resonant rotational peaks within the S-branch of the C3Π, (v = 2) ← X3Σ(v' = 0) absorption band of O2. The efficient ionization of O2 liberates electrons that induce electron avalanche ionization of local N2 molecules generating N2 +, which primarily deexcites via photoemissions of the first negative band of N2+(B 2 Σ u+-X 2 Σ g+). When sufficient lasing energy is used, the ionization region and subsequent photoemission signal is achieved along a 1D line thus, if directly imaged can allow for gas temperature assignments along said line; demonstrated here of up to five centimeters in length. The temperature gradients present within the ensuing shock train of a supersonic under expanded free jet serves as a basis of characterization for this new RIPT imaging scheme. The O2 RIPT results are extensively compared and validated against well-known and established techniques (i.e., CARS and CFD). The direct imaging capability fully realizes the technique's fundamental potential and is expected to be the standard of implementation going forward. The direct imaging capability can play instrumental roles in future scientific studies that rely upon acute characterization of thermal gradients within a medium that cannot be easily resolved by a point. Furthermore, the removal of the spectrometer greatly reduces the cost, complexity, and optical alignment associated with prior RIPT measurements.

Estimation for a complex index of refraction based on the Stokes vector of the reflected light under active polarized detection.

An estimation method for a complex index of refraction based on the Stokes vector of the reflected light under active polarized detection is presented. In this method, the difference of the Stokes vector of the reflected light is used to introduce the three new estimation indices for the L-M nonlinear least squares algorithm to estimate the complex index of refraction n and k of the target, which does not require either interpretation of the diffuse reflection part or calculation of every polarized bidirectional reflection distribution function (pBRDF) matrix element. Aluminum is chosen to be the sample to prove the principle of this method, and the result shows that this method can estimate the complex index of refraction more precisely compared with the Hyde method. The result further shows that the estimation index containing elements related to circular polarization has better performance than the index only containing elements related to linear polarization.

Air resonance enhanced multiphoton ionization tagging velocimetry.

Air resonance enhanced multiphoton ionization (REMPI) tagging velocimetry (ART) was demonstrated in quiescent and supersonic flows. The ART velocimetry method utilizes a wavelength tunable laser beam to resonantly ionize molecular oxygen in air and generate additional avalanche-type ionization of molecular nitrogen. The fluorescence emissions from the first negative and first positive bands of molecular nitrogen are, thus, produced and used for flow tagging. Detailed characterization of ART was conducted, including the effects of oxygen resonance to fluoresce nitrogen, nitrogen fluorescence spectrum, laser energy deposition into quiescent flow showing minimal perturbations in flow, fluorescence lifetime study at various pressures, and line tagging without breakdown. Pointwise velocity measurements within a supersonic flow from a nominal Mach 1.5 nozzle have been conducted and characterized.

Modified Reconstruction of Brown II Defects With Anterolateral Thigh Flaps Following Tumor Resection.

OBJECTIVE: Maxillary defects reconstructed with flaps usually cause nasalomaxillary fistula, discomfort oral lining, and poor function of denture. To resolve these problems, this study introduces a modified method of anterolateral thigh flap (ALTF) with skin and myofascial paddles to reconstruct nasal and oral lining of maxillary defects. METHODS: This study retrospectively reviewed 66 consecutive patients of Brown II maxillary defects following tumor resection reconstructed with ALTFs of modified or conventional methods. In modified group, oral lining was reconstructed with myofascial paddle and nasal lining was reconstructed with skin paddle. The functional and aesthetic outcomes, and the scores based on the University of Washington quality of life questionnaire were assessed. RESULTS: All flaps were successful in reconstruction of Brown II maxillary defects. No nasalomaxillary fistula and obstruction of the nasal cavity were found in modified ALTFs group. The functions of removable denture were better in modified ALTFs group. There was no significant difference about tumor recurrence, range of mouth opening, and aesthetic outcomes between the 2 groups. CONCLUSIONS: The modified method of ALTF with skin and myofascial piddle to reconstruct Brown IIa and IIb defects following tumor resection is simple and reliable, which improves the oral comfortability and function of denture, and avoids obstruction of the nasal cavity.

A Synergistic DNA-polydopamine-MnO2 Nanocomplex for Near-Infrared-Light-Powered DNAzyme-Mediated Gene Therapy.

DNAzyme is emerging for gene therapy. The administration of the in vivo catalytic activity of DNAzyme has proven important but challenging for clinical applications. Herein, we report a synergistic DNA-polydopamine-MnO2 nanocomplex, which enables near-infrared (NIR)-light-powered catalytic activity of DNAzyme in vivo. The nanocomplex has a hierarchical structure: a DNA nanoframework as the scaffold and polydopamine-MnO2 (PM) as the coating layer. The DNA nanoframework contains repeated DNAzyme sequences. PM assembles on the surface of the DNA nanoframework. When the nanocomplex accumulates at tumor sites, upon NIR-light radiation, polydopamine induces a temperature elevation at tumor sites via photothermal conversion; meanwhile, glutathione triggers decomposition of PM to release Mn2+ to activate DNAzyme in the cytoplasm for gene regulation. In vitro and in vivo experiments show that the PM-induced temperature elevation enhances the Egr-1 mRNA cleavage activity of DNAzyme, promoting downregulation of the Egr-1 protein in tumor cells. In addition, the temperature elevation induces heat stress, achieving a synergistic tumor ablation effect.

MAGNet: A Camouflaged Object Detection Network Simulating the Observation Effect of a Magnifier.

In recent years, protecting important objects by simulating animal camouflage has been widely employed in many fields. Therefore, camouflaged object detection (COD) technology has emerged. COD is more difficult to achieve than traditional object detection techniques due to the high degree of fusion of objects camouflaged with the background. In this paper, we strive to more accurately and efficiently identify camouflaged objects. Inspired by the use of magnifiers to search for hidden objects in pictures, we propose a COD network that simulates the observation effect of a magnifier called the MAGnifier Network (MAGNet). Specifically, our MAGNet contains two parallel modules: the ergodic magnification module (EMM) and the attention focus module (AFM). The EMM is designed to mimic the process of a magnifier enlarging an image, and AFM is used to simulate the observation process in which human attention is highly focused on a particular region. The two sets of output camouflaged object maps were merged to simulate the observation of an object by a magnifier. In addition, a weighted key point area perception loss function, which is more applicable to COD, was designed based on two modules to give greater attention to the camouflaged object. Extensive experiments demonstrate that compared with 19 cutting-edge detection models, MAGNet can achieve the best comprehensive effect on eight evaluation metrics in the public COD dataset. Additionally, compared to other COD methods, MAGNet has lower computational complexity and faster segmentation. We also validated the model's generalization ability on a military camouflaged object dataset constructed in-house. Finally, we experimentally explored some extended applications of COD.

Linear array focused-laser differential interferometry for single-shot multi-point flow disturbance measurements.

In this Letter, a modification of the well-known focused-laser differential interferometer (FLDI) is demonstrated, with the primary focus being increasing the number of probed locations efficiently. To generate multiple beams in the FLDI system, a diffractive optical element is used. This approach is significantly more cost-effective and easier to implement than the current approach of generating multiple FLDI beam pairs using a series of Wollaston prisms. The measurements shown here utilize a 1D linear array of points, and the ability to generate a 2D array is demonstrated using two linear diffractive optical elements in tandem. Therefore, this technique, referred to as linear array FLDI (LA-FLDI), is able to provide measurements of fluid disturbances at multiple discrete locations while allowing for high data acquisition rates (>1MHz). This technique provides a much simpler approach to multipoint FLDI measurements and can increase the throughput of FLDI measurements in impulse aerospace testing facilities.

Picosecond laser electronic excitation tagging velocimetry using a picosecond burst-mode laser.

Detailed characterizations of picosecond laser electronic excitation tagging (PLEET) in pure nitrogen (N2) and air with a 24 ps burst-mode laser system have been conducted. The burst-mode laser system is seeded with a 200 fs broadband seeding laser to achieve short pulse duration. As a non-intrusive molecular tagging velocimetry (MTV) technique, PLEET achieves "writing" via photo-dissociating nitrogen molecules and "tracking" by imaging the molecular nitrogen emissions. Key characteristics and performance of utilization of a 24 ps pulse-burst laser for MTV were obtained, including lifetime of the nitrogen emissions, power dependence, pressure dependence, and local flow heating by the laser pulses. Based on the experimental results and physical mechanisms of PLEET, 24 ps PLEET can produce similar 100 kHz molecular nitrogen emissions by photodissociation, while generating less flow disturbance by reducing laser joule heating than 100 ps PLEET.