Clinical features and multiomics profiles indicate coagulation and platelet dysfunction in COVID-19 viral sepsis.

Increased cases of sepsis during COVID-19 in the absence of known bacterial pathogens highlighted role of viruses as causative agents of sepsis. In this study, we investigated clinical, laboratory, proteomic, and metabolomic characteristics of viral sepsis patients (n = 45) and compared them to non-sepsis patients with COVID-19 (n = 186) to identify molecular mechanisms underlying the pathology of viral sepsis in COVID-19. We identified unique metabolomic and proteomic signatures that suggest a substantial perturbation in the coagulation, complement, and platelet activation pathways in viral sepsis. Our proteomic data indicated elevated coagulation pathway protein (fibrinogen), whereas a decrease in many of the complement proteins was observed. These alterations were associated with the functional consequences such as susceptibility to secondary bacterial infections and potentially contributing to both local and systemic disease phenotypes. Our data provide novel aspect of COVID-19 pathology that is centered around presence of sepsis phenotype in COVID-19.

Nanofluidic Membrane-Assisted Organic Electrochemical Transistors for Bioinspired Gustatory Sensation Based on Selective Cation Transport.

Natural organisms have evolved precise sensing systems relying on unique ion channels, which can efficiently perceive various physical/chemical stimuli based on ionic signal transmission in biological fluid environments. However, it is still a huge challenge to achieve extensive applications of the artificial counterparts as an efficient wet sensing platform due to the fluidity of the working medium. Herein, nanofluidic membranes with selective cation transport properties and solid-state organic electrochemical transistors (OECTs) with amplified signals are integrated together to mimic human gustatory sensation, achieving ionic gustatory reagent recognition and a portable configuration. Cu-HHTP nanofluidic membranes with selective cation transport through their uniform micropores are constructed first, followed by assembly with OECTs to form the designed nanofluidic membrane-assisted OECTs (nanofluidic OECTs). As a result, they can distinguish typically ionic gustatory reagents, and even ionic liquids (ILs), demonstrating enhanced gustatory perception performance under a wide concentration range (10-7-10-1 m) compared with those of conventional OECTs. The linear correlations between the response and the reagent concentration further indicate the promising potential for practical application as a next-generation sensing platform. It is suggested that nanofluidic membranes mediated intramembrane cation transport based on the steric hindrance effect, resulting in distinguishable and improved response to multiple ions.

Design and Development of Metasurface Materials for Enhancing Photodetector Properties.

Recently, metasurface-based photodetectors (metaphotodetectors) have been developed and applied in various fields. Metasurfaces are artificial materials with unique properties that have emerged over the past decade, and photodetectors are powerful tools used to quantify incident electromagnetic wave information by measuring changes in the conductivity of irradiated materials. Through an efficient microstructural design, metasurfaces can effectively regulate numerous characteristics of electromagnetic waves and have demonstrated unique advantages in various fields, including holographic projection, stealth, biological image enhancement, biological sensing, and energy absorption applications. Photodetectors play a crucial role in military and civilian applications; therefore, efficient photodetectors are essential for optical communications, imaging technology, and spectral analysis. Metaphotodetectors have considerably improved sensitivity and noise-equivalent power and miniaturization over conventional photodetectors. This review summarizes the advantages of metaphotodetectors based on five aspects. Furthermore, the applications of metaphotodetectors in various fields including military and civil applications, are systematically discussed. It highlights the potential future applications and developmental trends of metasurfaces in metaphotodetectors, provides systematic guidance for their development, and establishes metasurfaces as a promising technology.

A novel bispecific peptide targeting PD-1 and PD-L1 with combined antitumor activity of T-cells derived from the patients with TSCC.

Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) are key immune checkpoints (ICs) that critically influence immunotherapy. Tumor resistance to single IC-targeting drugs has increased interest in dual-target drugs, which have shown feasibility for cancer treatment. In this study, we aimed to develop dual-target peptide drugs targeting the PD-1/PD-L1 pathway and to evaluate their efficacy compared to functional antibodies in enhancing the cytotoxicity of human T cells against tongue squamous carcinoma cell lines. Through sequence analysis and peptide truncation, we modified a pre-existing peptide named nABPD-1 targeting PD-1. Subsequently, we obtained two novel peptides named nABPD-2 and nABPD-3, with nABPD-2 showing an enhanced affinity for human PD-1 protein compared to nABPD-1. Importantly, nABPD-2 exhibited dual-targeting capability, possessing a high affinity for both PD-L1 and PD-1. Furthermore, nABPD-2 effectively promoted the cytotoxicity of human T cells against tongue squamous carcinoma cell lines, surpassing the efficacy of anti-PD-1 or anti-PD-L1 functional antibodies alone. Considering that nABPD-2 has lower production costs and dose requirements, it can potentially be used in therapeutic applications.

Spatial distribution of metabolites in processing Ziziphi Spinosae Semen as revealed by matrix-assisted laser desorption/ionization mass spectrometry imaging.

Ziziphi Spinosae Semen (ZSS) is the first choice for the treatment of insomnia. This research aimed to reveal the spatial distribution of identifying quality markers of ZSS and to illustrate the metabolite quality characteristics of this herbal medicine. Here, we performed a matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) in situ to detect and image 33 metabolites in ZSS, including three saponins, six flavonoids, four alkaloids, eight fatty acids, and 12 amino acids. The MALDI images of the metabolites clearly showed the heterogeneous spatial distribution in different regions of ZSS tissues, such as the cotyledon, endosperm, and radicle. The distribution area of two saponins, six flavonoids, and three alkaloids increased significantly after the fried processing of ZSS. Based on the ion images, samples with different processing technologies were distinguished unambiguously by the pattern recognition method of orthogonal partial least squares discrimination analysis (OPLS-DA). Simultaneously, 23 major influencing components exerting higher ion intensities were identified as the potential quality markers of ZSS. Results obtained in the current research demonstrate that the processing of ZSS changes its content and distribution of the medicinal components. The analysis of MALDI-MSI provides a novel MS-based molecular imaging approach to investigate and monitor traditional medicinal plants.

Improved efficacy of cisplatin delivery by peanut agglutinin­modified liposomes in non­small cell lung cancer.

Globally, non­small cell lung cancer (NSCLC) is a significant threat to human health, and constitutes >80% of lung cancer cases. Cisplatin (CDDP), a commonly used drug in clinical treatment, has been the focus of research aiming to mitigate its potent toxicity through encapsulation within liposomes. However, challenges, such as a reduced drug loading efficiency and nonspecific release, have emerged as obstacles. The present study aimed to improve the encapsulation efficiency of CDDP within liposomes by pre­preparation of CDDP and modifying the liposome surface through the incorporation of peanut agglutinin (PNA) as a ligand [CDDP­loaded PNA­modified liposomes (CDDP­PNA­Lip)]. This strategy was designed to enhance the delivery of CDDP to tumour tissues, thereby reducing associated side effects. The effect of CDDP­PNA­Lip on the proliferation and migration of NSCLC cell lines with high MUC1 expression was elucidated through in vitro studies. Additionally, the capacity of PNA modification to augment the targeted anti­tumour efficacy of liposomes was assessed through xenograft tumour experiments. The results indicated that in an in vitro uptake assay Rhodamine B (RhB)­loaded PNA­modified liposomes were taken up by cells with ~50% higher efficiency compared with free RhB. In addition, CDDP­PNA­Lip resulted in a 2.65­fold enhancement of tumour suppression in vivo compared with free CDDP. These findings suggested that the encapsulation of CDDP within ligand­modified liposomes may significantly improve its tumour­targeting capabilities, providing valuable insights for clinical drug development.

High-Temperature Anomalous Metal States in Iron-Based Interface Superconductors.

The nature of the anomalous metal state has been a major puzzle in condensed matter physics for more than three decades. Here, we report systematic investigation and modulation of the anomalous metal states in high-temperature interface superconductor FeSe films on SrTiO_{3} substrate. Remarkably, under zero magnetic field, the anomalous metal state persists up to 20 K in pristine FeSe films, an exceptionally high temperature standing out from previous observations. In stark contrast, for the FeSe films with nanohole arrays, the characteristic temperature of the anomalous metal state is considerably reduced. We demonstrate that the observed anomalous metal states originate from the quantum tunneling of vortices adjusted by the Ohmic dissipation. Our work offers a perspective for understanding the origin and modulation of the anomalous metal states in two-dimensional bosonic systems.

Promoter hypermethylation-induced downregulation of ITGA7 promotes colorectal cancer proliferation and migration by activating the PI3K/AKT/NF-κB pathway.

We previously reported that integrin alpha 7 (ITGA7) was downregulated in colorectal cancer (CRC) tissues and CRC cell lines and that the lower expression of ITGA7 in CRC tissues was correlated with distant metastasis, suggesting that ITGA7 may function as a suppressor in CRC. The present research was conducted to further investigate the role and mechanisms of ITGA7 in CRC progression. First, bisulfite modification and genomic sequencing (BSP) results showed that the methylation rate of ITGA7 promoter was higher in 10 CRC tissues than in the matched normal tissues. Additionally, 5-Aza-CdR treatment increased ITGA7 expression in CRC cells. Gain-of-function assays revealed the inhibitory role of ITGA7 in CRC cell proliferation and migration. Mechanistically, RNA sequencing, RT-qPCR, and cytoplasm and nuclear separation and rescue assays indicated that knockdown of ITGA7 activated the transcription of MMP9, SETD7, and ADAM15 by enhancing the nuclear translocation of NF-κB. Moreover, CoIP and Western blot suggested a mechanistic model in which ITGA7 binds to CKAP4 to block the interaction of CKAP4 and PI3K p85α and thereby suppress the PI3K/AKT/NF-κB pathway. Accordingly, the current study suggests that ITGA7 functions as a suppressor in CRC progression and that its expression is controlled by promoter methylation.

Characterization of two virulent Salmonella phages and transient application in egg, meat and lettuce safety.

Salmonella, a prominent foodborne pathogen, has posed enduring challenges to the advancement of food safety and global public health. The escalating concern over antibiotic misuse, resulting in the excessive presence of drug residues in animal-derived food products, necessitates urgent exploration of alternative strategies for Salmonella control. Bacteriophages emerge as promising green biocontrol agents against pathogenic bacteria. This study delineates the identification of two novel virulent Salmonella phages, namely phage vB_SalS_ABTNLsp11241 (referred to as sp11241) and phage 8-19 (referred to as 8-19). Both phages exhibited efficient infectivity against Salmonella enterica serotype Enteritidis (SE). Furthermore, this study evaluated the effectiveness of two phages to control SE in three different foods (whole chicken eggs, raw chicken meat, and lettuce) at different MOIs (1, 100, and 10000) at 4°C. It's worth noting that sp11241 and 8-19 achieved complete elimination of SE on eggs after 3 h and 6 h at MOI = 100, and after 2 h and 5 h at MOI = 10000, respectively. After 12 h of treatment with sp11241, a maximum reduction of 3.17 log10 CFU/mL in SE was achieved on raw chicken meat, and a maximum reduction of 3.00 log10 CFU/mL was achieved on lettuce. Phage 8-19 has the same effect on lettuce as sp11241, but is slightly less effective than sp11241 on chicken meat (a maximum 2.69 log10 CFU/mL reduction). In conclusion, sp11241 and 8-19 exhibit considerable potential for controlling Salmonella contamination in food at a low temperature and represent viable candidates as green antibacterial agents for food applications.

Efficient preparation of anisotropic cellulose sponge from cotton stalks: An excellent material for separation applications.

Water pollution and solid waste resource reuse demand immediate attention and research. Here, we present a method to create anisotropic cellulose sponges from cotton stalk waste. Using the inherent structure of cotton stalks, we selectively remove lignin and hemicellulose via acid and alkali pretreatment. This process yields cellulose sponges with a natural pore structure. Our findings demonstrate that these sponges retain the original pore configuration of cotton stalks, providing excellent connectivity and compressibility due to their unique anisotropic three-dimensional structure. Moreover, these sponges exhibit exceptional super-hydrophilic and underwater super-oleophobic properties, with underwater oil contact angles exceeding 150° for all tested oils. External pressure can reduce the pore size of the cellulose sponge, facilitating the gravity-driven separation and removal of dyes and emulsions. Remarkably, removal efficiencies for Methylene Blue (MB), Congo Red (CR), water-in-oil (w/o) emulsions, and oil-in-water (o/w) emulsions exceed 99 %, 97 %, 99 %, and 99 %, respectively, highlighting superior removal and recyclability. Further investigation into the mechanisms of dye and emulsion removal employs X-ray photoelectron spectroscopy (XPS) characterization and molecular dynamics (MD) simulation. These insights lay the groundwork for the efficient recycling and resource utilization of waste cotton stalks, offering promising applications in water purification.

A bibliometric analysis of the knowledge related to mental health during and post COVID-19 pandemic.

Objective: COVID-19 led to a horrific global pandemic, with strict lockdowns and prolonged indoor stays increasing the risk of mental health problems, affecting people of different ages, genders, regions, and types of work to varying degrees. This study provides a bibliometric summary of the knowledge map related to mental health during and post COVID-19 pandemic. Methods: Publications related to mental health during and post COVID-19 pandemic were searched in the Web of Science Core Collection (WoSCC) database through March 19, 2024. After screening the search results, the literature included in the final was first quantitatively analyzed using GraphPad Prism software and then visualized using VOSviewer, CiteSpace, and R (the bibliometrix package). Results: The 7,047 publications from 110 countries were included, with the highest number of publications from China and the United States, and the number of publications related to mental health during and post the COVID-19 pandemic increased annually until 2023, after which it began to decline. The major institutions were University of Toronto, University of London, Harvard University, King's College London, University College London, University of California System, University of Melbourne, Institut National De La Sante Et De La Recherche Medicale (Inserm), Mcgill University, and University of Ottawa; Frontiers in Psychiatry had the highest number of publications, and the Journal of Affective Disorders had the highest number of co-citations; 36,486 authors included, with Xiang, Yu-Tao, Cheung, Teris, Chung, Seockhoon published the most papers, and World Health Organization, Kroenke K, and Wang CY were the most co-cited; epidemiologically relevant studies on mental health related to COVID-19, and the importance of mental health during normalized epidemic prevention and control are the main directions of this research area, especially focusing on children's mental health; "pandemic," "sars-cov-2," "epidemic," "depression," "coronavirus anxiety," "anxiety," "longitudinal," "child," "coronavirus anxiety," "longitudinal," "child," and "coronavirus" are the top keywords in recent years. Conclusion: This comprehensive bibliometric study summarizes research trends and advances in mental health during and after the COVID-19 Pandemic. It serves as a reference for mental health research scholars during and after the COVID-19 pandemic, clarifying recent research preoccupations and topical directions.

In situ growth of HKUST-1 on electrospun polyacrylonitrile nanofibers/regenerated cellulose aerogel for efficient methylene blue adsorption.

Dyes, as organic pollutants, are causing increasingly severe environmental problems. Metal-organic frameworks (MOFs) are considered promising dye adsorbents; however, their application is limited due to their powder or solid particle forms and limited reusability. Therefore, this study proposes an innovative approach to develop a novel MOF-based composite aerogel, specifically a HKUST-1/polyacrylonitrile nanofibers/regenerated cellulose (HKUST-1/PANNs/RC) composite aerogel adsorbent, for the adsorption of pollutants in water. This adsorbent was successfully prepared using a simple method combining covalent crosslinking, quick freezing, freeze-drying, in-situ growth synthesis, and solvothermal techniques. The HKUST-1/PANNs/RC composite aerogel exhibits a significantly large specific surface area, which is approximately 64 times greater than that of PANNs/RC (10.45 m2·g-1), with a specific surface area of 669.9 m2·g-1. The PANNs serve as a support framework, imparting excellent mechanical properties to the composite aerogel, enhancing its overall stability and recoverability. Additionally, the composite aerogel contains numerous -COOH and -OH groups on its surface, providing strong acid resistance and facilitating interactions with pollutant molecules through electrostatic interactions, π-π conjugation, n-π* interactions, and hydrogen bonding, thereby promoting the adsorption process. Using methylene blue (MB) as a probe molecule, the study results demonstrate that the HKUST-1/PANNs/RC composite aerogel has an adsorption capacity of 522.01 mg·g-1 for MB (25 h), exhibiting excellent adsorption performance. This composite aerogel shows great potential for application in water pollution control.

Characterizing Retinal Sensitivity and Structure in Congenital Stationary Night Blindness: A Combined Microperimetry and OCT Study.

Purpose: To investigate the characteristics of microperimetry and optical coherence tomography (OCT) in congenital stationary night blindness (CSNB), as well as their structure-function association. Methods: This cross-sectional study included 32 eyes from 32 participants with CSNB, comprising 18 with complete CSNB and 14 with incomplete CSNB, along with 36 eyes from 36 CSNB-unaffected controls matched for age, sex, and spherical equivalent. Using MP-3 microperimetry, central retinal sensitivity was assessed within a 20° field, distributed across six concentric rings (0°, 2°, 4°, 6°, 8°, and 10°). OCT was used to analyze retinal and choroidal thickness. The study aimed to assess the overall and ring-wise retinal sensitivity, as well as choroidal and retinal thickness in CSNB and CSNB-unaffected controls, with a secondary focus on the relationship between retinal sensitivity and microstructural features on OCT. Results: In comparison with CSNB-unaffected subjects, the overall and ring-wise retinal sensitivity as well as choroidal thickness were reduced in patients with CSNB (P < 0.001). Moreover, the central sensitivity in incomplete CSNB group was lower than in complete CSNB group (25.72 ± 3.93 dB vs. 21.92 ± 4.10 dB; P < 0.001). The retinal thickness in the CSNB group was thinner outside the fovea compared with the CSNB-unaffected group. Multiple mixed regression analyses revealed that point-to-point retinal sensitivity was significantly correlated with BCVA (P = 0.002) and the corresponding retinal thickness (P = 0.004). Conclusions: Examination of retinal sensitivity and OCT revealed different spatial distribution profiles in CSNB and its subtypes. In CSNB eyes, retinal sensitivity on microperimetry was associated with retinal thickness on OCT.

Sensitive Detection and Differentiation of Biologically Active Ricin and Abrin in Complex Matrices via Specific Neutralizing Antibody-Based Cytotoxicity Assay.

Ricin and abrin are highly potent plant-derived toxins, categorized as type II ribosome-inactivating proteins. High toxicity, accessibility, and the lack of effective countermeasures make them potential agents in bioterrorism and biowarfare, posing significant threats to public safety. Despite the existence of many effective analytical strategies for detecting these two lethal toxins, current methods are often hindered by limitations such as insufficient sensitivity, complex sample preparation, and most importantly, the inability to distinguish between biologically active and inactive toxin. In this study, a cytotoxicity assay was developed to detect active ricin and abrin based on their potent cell-killing capability. Among nine human cell lines derived from various organs, HeLa cells exhibited exceptional sensitivity, with limits of detection reaching 0.3 ng/mL and 0.03 ng/mL for ricin and abrin, respectively. Subsequently, toxin-specific neutralizing monoclonal antibodies MIL50 and 10D8 were used to facilitate the precise identification and differentiation of ricin and abrin. The method provides straightforward and sensitive detection in complex matrices including milk, plasma, coffee, orange juice, and tea via a simple serial-dilution procedure without any complex purification and enrichment steps. Furthermore, this assay was successfully applied in the unambiguous identification of active ricin and abrin in samples from OPCW biotoxin exercises.

Hydrogel Wound Dressings Accelerating Healing Process of Wounds in Movable Parts.

Skin is the largest organ in the human body and requires proper dressing to facilitate healing after an injury. Wounds on movable parts, such as the elbow, knee, wrist, and neck, usually undergo delayed and inefficient healing due to frequent movements. To better accommodate movable wounds, a variety of functional hydrogels have been successfully developed and used as flexible wound dressings. On the one hand, the mechanical properties, such as adhesion, stretchability, and self-healing, make these hydrogels suitable for mobile wounds and promote the healing process; on the other hand, the bioactivities, such as antibacterial and antioxidant performance, could further accelerate the wound healing process. In this review, we focus on the recent advances in hydrogel-based movable wound dressings and propose the challenges and perspectives of such dressings.

Mechanism Analysis of OsZF8-Mediated Regulation of Rice Resistance to Sheath Blight.

Transcription factors are key molecules involved in transcriptional and post-transcriptional regulation in plants and play an important regulatory role in resisting biological stress. In this study, we identified a regulatory factor, OsZF8, mediating rice response to Rhizoctonia solani (R. solani) AG1-IA infection. The expression of OsZF8 affects R. solani rice infection. OsZF8 knockout and overexpressed rice plants were constructed, and the phenotypes of mutant and wild-type (WT) plants showed that OsZF8 negatively regulated rice resistance to rice sheath blight. However, it was speculated that OsZF8 plays a regulatory role at the protein level. The interacting protein PRB1 of OsZF8 was screened using the yeast two-hybrid and bimolecular fluorescence complementation test. The results showed that OsZF8 effectively inhibited PRB1-induced cell death in tobacco cells, and molecular docking results showed that PRB1 had a strong binding effect with OsZF8. Further, the binding ability of OsZF8-PRB1 to ergosterol was significantly reduced when compared with the PRB1 protein. These findings provide new insights into elucidating the mechanism of rice resistance to rice sheath blight.

A Novel Ubiquitin Ligase Adaptor PTPRN Suppresses Seizure Susceptibility through Endocytosis of NaV1.2 Sodium Channels.

Intrinsic plasticity, a fundamental process enabling neurons to modify their intrinsic properties, plays a crucial role in shaping neuronal input-output function and is implicated in various neurological and psychiatric disorders. Despite its importance, the underlying molecular mechanisms of intrinsic plasticity remain poorly understood. In this study, a new ubiquitin ligase adaptor, protein tyrosine phosphatase receptor type N (PTPRN), is identified as a regulator of intrinsic neuronal excitability in the context of temporal lobe epilepsy. PTPRN recruits the NEDD4 Like E3 Ubiquitin Protein Ligase (NEDD4L) to NaV1.2 sodium channels, facilitating NEDD4L-mediated ubiquitination, and endocytosis of NaV1.2. Knockout of PTPRN in hippocampal granule cells leads to augmented NaV1.2-mediated sodium currents and higher intrinsic excitability, resulting in increased seizure susceptibility in transgenic mice. Conversely, adeno-associated virus-mediated delivery of PTPRN in the dentate gyrus region decreases intrinsic excitability and reduces seizure susceptibility. Moreover, the present findings indicate that PTPRN exerts a selective modulation effect on voltage-gated sodium channels. Collectively, PTPRN plays a significant role in regulating intrinsic excitability and seizure susceptibility, suggesting a potential strategy for precise modulation of NaV1.2 channels' function.

Developing high resistant starch content rice noodles with superior quality: A method using modified rice flour and psyllium fiber.

The effects of high-resistant starch (RS) content rice flour, psyllium husk powder (PHP), and psyllium powder (PP) on the edible quality and starch digestibility of rice noodles were investigated in this study. High-RS rice noodles showed lower digestibility but poor edible quality. With the addition of PHP and PP, high-RS rice noodles' cooking and texture quality were improved significantly, especially the breakage rates, cooking losses, and chewiness (P < 0.05). Compared to traditional white rice noodle's estimated glycemic index (eGI) of 86.69, the eGI values for 5PHP-RN and 5PHP-2PP-RN were significantly decreased to 66.74 and 65.77, achieving a medium GI status (P < 0.05). This resulted from the high amylose and lipid content in the modified rice flour and psyllium, leading to increase of starch crystallinity. Besides, based on the analysis of Pearson's correlation, it can be found that PHP rich in insoluble dietary fiber (IDF) could improve high-RS noodle cooking and texture quality better, while PP rich in soluble dietary fiber (SDF) can further reduce the RDS content and its starch digestibility. Therefore, utilizing modified rice flour with an appropriate addition of PHP and PP can be considered an effective strategy for producing superior-quality lower glycemic index rice noodles.

Impact of babyface schema on time perception: Insights from neutral and crying facial expressions.

Facial expressions in infants have been noted to create a spatial attention bias when compared with adult faces. Yet, there is limited understanding of how adults perceive the timing of infant facial expressions. To investigate this, we used both infant and adult facial expressions in a temporal bisection task. In Experiment 1, we compared duration judgments of neutral infant and adult faces. The results revealed that participants felt that neutral infant faces lasted for a shorter time than neutral adult faces, independent of participant sex. Experiment 2 employed sad (crying) facial expressions. Here, the female participants perceived that the infants' faces were displayed for a longer duration than the adults' faces, whereas this distinction was not evident among the male participants. These findings highlight the influence of the babyface schema on time perception, nuanced by emotional context and sex-based individual variances.