Biosynthesis of fungus-based oral selenium microcarriers for radioprotection and immuno-homeostasis shaping against radiation-induced heart disease.

Radiation-induced heart disease (RIHD), characterized by severe oxidative stress and immune dysregulation, is a serious condition affecting cancer patients undergoing thoracic radiation. Unfortunately, clinical interventions for RIHD are lacking. Selenium (Se) is a trace element with excellent antioxidant and immune-modulatory properties. However, its application in heart radioprotection remains challenging. Herein, we developed a novel bioactive Cordyceps militaris-based Se oral delivery system (Se@CM), which demonstrated superior radioprotection effects in vitro against X-ray-induced damage in H9C2 cells through suppressing excessive ROS generation, compared to the radioprotectant Amifostine. Moreover, Se@CM exhibited exceptional cardioprotective effects in vivo against X-ray irradiation, reducing cardiac dysfunction and myocardial fibrosis by balancing the redox equilibrium and modulating the expression of Mn-SOD and MDA. Additionally, Se@CM maintained immuno-homeostasis, as evidenced by the upregulated population of T cells and M2 macrophages through modulation of selenoprotein expression after irradiation. Together, these results highlight the remarkable antioxidant and immunity modulation properties of Se@CM and shed light on its promising application for cardiac protection against IR-induced disease. This research provides valuable insights into developing effective strategies for preventing and managing RIHD.

In Situ Atomic Reconstruction Engineering Modulating Graphene-Like MXene-Based Multifunctional Electromagnetic Devices Covering Multi-Spectrum.

With the diversified development of big data, detection and precision guidance technologies, electromagnetic (EM) functional materials and devices serving multiple spectrums have become a hot topic. Exploring the multispectral response of materials is a challenging and meaningful scientific question. In this study, MXene/TiO2 hybrids with tunable conduction loss and polarization relaxation are fabricated by in situ atomic reconstruction engineering. More importantly, MXene/TiO2 hybrids exhibit adjustable spectral responses in the GHz, infrared and visible spectrums, and several EM devices are constructed based on this. An antenna array provides excellent EM energy harvesting in multiple microwave bands, with |S11| up to - 63.2 dB, and can be tuned by the degree of bending. An ultra-wideband bandpass filter realizes a passband of about 5.4 GHz and effectively suppresses the transmission of EM signals in the stopband. An infrared stealth device has an emissivity of less than 0.2 in the infrared spectrum at wavelengths of 6-14 µm. This work can provide new inspiration for the design and development of multifunctional, multi-spectrum EM devices.

Heterodimensional Structure Switching Multispectral Stealth and Multimedia Interaction Devices.

Lightweight and flexible electronic materials with high energy attenuation hold an unassailable position in electromagnetic stealth and intelligent devices. Among them, emerging heterodimensional structure draws intensive attention in the frontiers of materials, chemistry, and electronics, owing to the unique electronic, magnetic, thermal, and optical properties. Herein, an intrinsic heterodimensional structure consisting of alternating assembly of 0D magnetic clusters and 2D conductive layers is developed, and its macroscopic electromagnetic properties are flexibly designed by customizing the number of oxidative molecular layer deposition (oMLD) cycles. This unique heterodimensional structure features highly ordered spatial distribution, with an achievement of electron-dipole and magnetic-dielectric double synergies, which exhibits the high attenuation of electromagnetic energy (160) and substantial improvement of dielectric loss tangent (≈200%). It can respond to electromagnetic waves of different bands to achieve multispectral stealth, covering visible light, infrared radiation, and gigahertz wave. Importantly, two kinds of ingenious information interaction devices are constructed with heterodimensional structure. The hierarchical antennas allow precise targeting of operating bands (S- to Ku- bands) by oMLD cycles. The strain imaging device with high sensitivity opens a new horizon for visual interaction. This work provides a creative insight for developing advanced micro-nano materials and intelligent devices.

Two new species of the genus Norellisoma Wahlgren, 1917 (Diptera, Scathophagidae) from Yintiaoling Nature Reserve, Chongqing, China.

The known species of the genus Norellisoma from China are reviewed and two new species from Yintiaoling Nature Reserve in Chongqing City, where no other Norellisoma species are recorded, are described: Norellisomawuxiensesp. nov., Norellisomayintiaoensesp. nov. A key to the species of Norellisoma from China is provided.

Thermally Derived Hierarchical Nanoplates for Electromagnetic Protection and Waste Energy Recovery Device.

With the advent of intelligent society and the popularity of electronic equipment, the protection and treatment of electromagnetic (EM) radiation have become hot research topics all over the world. Herein, novel 2D carbon-based nanoplates with uniformly embedded Co nanoparticles are prepared, with unique hierarchical structure and integrated magnetic-dielectric components. The obtained hierarchical nanoplates exhibit a wide range of tunable EM properties (ε' for 3.38 to 34.67 and ε″ for 0.13 to 31.45) by manipulating the dispersed states inside wax system, which can achieve an effective switch from microwave absorption to EM interference shielding performance. The optimal reflection loss reaches -55.6 dB, and the shielding efficiency is 93.5%. Meanwhile, the hierarchical nanoplates also exhibit impressive capacitive performance, with a specific capacitance of 1654 F g-1 at 1 A g-1 . Based on this, a creative device is constructed with the nanoplates, which can convert harmful EM radiation to useful electric energy for recycling. This work offers a new idea for the development of EM materials and functional devices, powerfully promoting the advance of energy and environmental fields.

T cell aging and Alzheimer's disease.

The brain has long been considered an immune-privileged organ due to the presence of the blood-brain barrier (BBB). However, recent discoveries have revealed the underestimated role of T cells in the brain through the meningeal lymphatic system. Age is the primary risk factor for Alzheimer's disease (AD), resulting in marked age-dependent changes in T cells. Manipulating peripheral T cell immune response has been shown to impact AD, but the relationship between T cell aging and AD remains poorly understood. Given the limited success of targeting amyloid beta (Aß) and the growing evidence of T cells' involvement in non-lymphoid organ aging, a deeper understanding of the relationship between T cells and AD in the context of aging is crucial for advancing therapeutic progress. In this review, we comprehensively examine existing studies on T cells and AD and offer an integrated perspective on their interconnections in the context of aging. This understanding can inform the development of new interventions to prevent or treat AD.

Assessment of adaptive immune responses of dairy cows with Burkholderia contaminans-induced mastitis.

Burkholderia contaminans, an emerging pathogen related to cystic fibrosis, is known to cause potentially fatal infections in humans and ruminants, especially in immunocompromised individuals. However, the immune responses in cows following its infection have not been fully elucidated. In this study, T- and B-lymphocytes-mediated immune responses were evaluated in 15 B. contaminans-induced mastitis cows and 15 healthy cows with multi-parameter flow cytometry. The results showed that infection with B. contaminans was associated with a significant decrease in the number and percentage of B lymphocytes but with a significant increase in the proportion of IgG+CD27+ B lymphocytes. This indicated that humoral immune response may not be adequate to fight intracellular infection, which could contribute to the persistent bacterial infection. In addition, B. contaminans infection induced significant increase of γδ T cells and double positive (DP) CD4+CD8+ T cells but not CD4+ or CD8+ (single positive) T cells in blood. Phenotypic analysis showed that the percentages of activated WC1+ γδ T cells in peripheral blood were increased in the B. contaminans infected cows. Interestingly, intracellular cytokine staining showed that cattle naturally infected with B. contaminans exhibited multifunctional TNF-α+IFN-γ+IL-2+ B. contaminans-specific DP T cells. Our results, for the first time, revealed a potential role of IgG+CD27+ B cells, CD4+CD8+ T cells and WC1+ γδ T cells in the defense of B. contaminans-induced mastitis in cows.

TRIB2 safeguards naive T cell homeostasis during aging.

Naive CD4+ T cells are more resistant to age-related loss than naive CD8+ T cells, suggesting mechanisms that preferentially protect naive CD4+ T cells during aging. Here, we show that TRIB2 is more abundant in naive CD4+ than CD8+ T cells and counteracts quiescence exit by suppressing AKT activation. TRIB2 deficiency increases AKT activity and accelerates proliferation and differentiation in response to interleukin-7 (IL-7) in humans and during lymphopenia in mice. TRIB2 transcription is controlled by the lineage-determining transcription factors ThPOK and RUNX3. Ablation of Zbtb7b (encoding ThPOK) and Cbfb (obligatory RUNT cofactor) attenuates the difference in lymphopenia-induced proliferation between naive CD4+ and CD8+ cells. In older adults, ThPOK and TRIB2 expression wanes in naive CD4+ T cells, causing loss of naivety. These findings assign TRIB2 a key role in regulating T cell homeostasis and provide a model to explain the lesser resilience of CD8+ T cells to undergo changes with age.

Enhanced efficiency of calcium-derived oleoyl serine on osteoporosis via Wnt/ß-catenin pathway.

Osteoporosis is a common disease of the elderly that affects millions of patients worldwide. It is mainly characterized by low bone mineral density and increased risk of fracture due to the deterioration of the bone structure, leading to difficulties in functional recovery, reduced quality of life, increased disability risk and mortality in the population. It has already been a major public health problem. Osteoporosis is a chronic disease that is difficult to treat in the elderly population, so it is crucial to develop new drugs for the treatment of osteoporosis. Oleoyl serine, an endogenous fatty acyl amide found in bone, has been shown to have excellent anti-osteoporosis effects, but it is easily hydrolyzed by amidases in vivo. The aim of this study is to determine the anti-osteoporotic effect of calcium-derived oleoyl serine, a novel oleoyl serine derivative and the molecular mechanism underneath. In vitro experiments demonstrated that calcium-derived oleoyl serine suppressed the expression of Fabp4, and Cebpα while Alp, and Runx2 was significantly upregulated compared with the oleoyl serine group and control. With the activation of ß-catenin, calcium-derived oleoyl serine restored the abnormal osteogenesis and lipogenesis, indicating calcium-derived oleoyl serine compared with oleoyl serine has better effects on promoting osteogenesis and suppressing lipogenesis. In vivo experiment agreed with these findings that calcium-derived oleoyl serine promotes osteogenesis and suppresses its lipogenesis to ameliorate osteoporosis via a ß-catenin dependent method. It is a new candidate for treating osteoporosis.

Aging-associated HELIOS deficiency in naive CD4+ T cells alters chromatin remodeling and promotes effector cell responses.

Immune aging combines cellular defects in adaptive immunity with the activation of pathways causing a low-inflammatory state. Here we examined the influence of age on the kinetic changes in the epigenomic and transcriptional landscape induced by T cell receptor (TCR) stimulation in naive CD4+ T cells. Despite attenuated TCR signaling in older adults, TCR activation accelerated remodeling of the epigenome and induced transcription factor networks favoring effector cell differentiation. We identified increased phosphorylation of STAT5, at least in part due to aberrant IL-2 receptor and lower HELIOS expression, as upstream regulators. Human HELIOS-deficient, naive CD4+ T cells, when transferred into human-synovium-mouse chimeras, infiltrated tissues more efficiently. Inhibition of IL-2 or STAT5 activity in T cell responses of older adults restored the epigenetic response pattern to the one seen in young adults. In summary, reduced HELIOS expression in non-regulatory naive CD4+ T cells in older adults directs T cell fate decisions toward inflammatory effector cells that infiltrate tissue.

The influence of three-dimensional structure on naïve T cell homeostasis and aging.

A breakdown in cellular homeostasis is thought to drive naïve T cell aging, however the link between naïve T cell homeostasis and aging in humans is poorly understood. To better address this, we developed a lymphoid organoid system that maintains resting naïve T cells for more than 2 weeks, in conjunction with high CD45RA expression. Deep phenotypic characterization of naïve T cells across age identified reduced CD45RA density as a hallmark of aging. A conversion from CD45RAhigh naive cells to a CD45RAlow phenotype was reproduced within our organoid system by structural breakdown, but not by stromal cell aging or reduced lymphocyte density, and mediated by alternative CD45 splicing. Together, these data suggest that external influences within the lymph node microenvironment may cause phenotypic conversion of naïve T cells in older adults.

Selenium Atom-Polarization Effect Determines TrxR-Specific Recognition of Metallodrugs.

Thioredoxin reductase (TrxR) is highly overexpressed in cancer cells to promote malignant tumor survival. Designing drugs that inhibit TrxR activity is a promising approach to achieve highly effective cancer chemotherapy. However, the selectivity of TrxR inhibitors continue to be a challenge for scientists. In this work, we demonstrate a new strategy to selectively inhibit TrxR through constructing electrophilic center -N-Se(δ+)-N- by using the polarization effect of the selenium atom. The constructed electrophilic center interacts noncovalently with the active motif of TrxR to avoid the interference of other residues in human tissues, thereby selectively inhibiting intracellular TrxR activity. Computational and experimental analysis confirms that the formed electrophilic selenium center preferred to attack the SeC residues in the redox active center of TrxR at the 498 site through strong noncovalent interactions. Both in vitro and in vivo experimental results confirmed that this strategy can significantly improve the anticancer effect. This study may provide a novel route to design highly effective and selective chemotherapeutic drugs.

Verbascoside: An Efficient and Safe Natural Antibacterial Adjuvant for Preventing Bacterial Contamination of Fresh Meat.

Inappropriate and disproportionate antibiotic use contributes immensely to the development of antibiotic resistance in bacterial species associated with food contamination. Therefore, alternative strategies to treat multidrug-resistant (MDR) bacterial infections are urgently needed. In this study, verbascoside was shown to exhibit excellent antibacterial activity and synergistic effects in combination with cell wall synthesis-inhibiting antibiotics, indicating that it can be used as an adjuvant to restore or increase the activity of antibiotics against resistant pathogens. In a mechanistic study, higher concentrations of verbascoside resulted in a longer lag phase and a lower specific exponential-phase growth rate of bacteria. Furthermore, verbascoside exerted its antimicrobial activity through multiple mechanisms, including cell membrane dysfunction, biofilm eradication and changes in cell morphology. The promising antibacterial activity and in vitro safety assessment results suggested that verbascoside can be used as a food additive for fresh meat preservation. Treatment with medium and high doses of verbascoside caused significant bacterial death in meat samples, slowed the spoilage rate, and extended the shelf life. Collectively, verbascoside is expected to be useful as an antibiotic adjuvant to prevent or treat resistant bacteria-related infections and an alternative novel antimicrobial additive in the food industry.

Dairy Cows Experimentally Infected With Bovine Leukemia Virus Showed an Increased Milk Production in Lactation Numbers 3-4: A 4-Year Longitudinal Study.

Bovine leukemia virus (BLV) is widespread in global cattle populations, but the effects of its infection on milk quantity and quality have not been clearly elucidated in animal models. In this study, 30 healthy first-lactation cows were selected from ≈2,988 cows in a BLV-free farm with the same criteria of parity, age, lactation number, as well as milk yield, SCS, and composition (fat, protein, and lactose). Subsequently, these cows were randomly assigned to the intervention (n = 15) or control (n = 15) group, and reared in different cowsheds. Cows in the intervention group were inoculated with 1 × phosphate-buffered solution (PBS) resuspended in peripheral blood mononuclear cells (PBMC) from a BLV-positive cow, while the controls were inoculated with the inactivated PBMC from the same individual. From June 2016 to July 2021, milk weight (kg) was automatically recorded by milk sensors, and milk SCS and composition were originated from monthly performed dairy herd improvement (DHI) testing. Fluorescence resonance energy transfer (FRET)-qPCR and ELISA showed that cows in the intervention group were successfully infected with BLV, while cows in the control group were free of BLV for the entire period. At 45 days post-inoculation (DPI), the numbers of whole blood cells (WBCs) (P = 0.010), lymphocytes (LYMs) (P = 0.002), and monocytes (MNCs) (P = 0.001) and the expression levels of IFN-γ (P = 0.013), IL-10 (P = 0.031), and IL-12p70 (P = 0.008) increased significantly in the BLV infected cows compared to the non-infected. In lactation numbers 2-4, the intervention group had significantly higher overall milk yield (P < 0.001), fat (P = 0.031), and protein (P = 0.050) than the control group, while milk SCS (P = 0.038) and lactose (P = 0.036) decreased significantly. Further analysis indicated that BLV infection was associated with increased milk yield at each lactation stage in lactation numbers 3-4 (P = 0.021 or P < 0.001), but not with SCS and milk composition. Together, this 4-year longitudinal study revealed that artificial inoculation of BLV increased the milk yield in cows in this BLV challenge model.

Tumor-Derived Membrane Vesicles: A Promising Tool for Personalized Immunotherapy.

Tumor-derived membrane vesicles (TDMVs) are non-invasive, chemotactic, easily obtained characteristics and contain various tumor-borne substances, such as nucleic acid and proteins. The unique properties of tumor cells and membranes make them widely used in drug loading, membrane fusion and vaccines. In particular, personalized vectors prepared using the editable properties of cells can help in the design of personalized vaccines. This review focuses on recent research on TDMV technology and its application in personalized immunotherapy. We elucidate the strengths and challenges of TDMVs to promote their application from theory to clinical practice.

IL-4 prevents adenosine-mediated immunoregulation by inhibiting CD39 expression.

The ectonucleotidase CD39 functions as a checkpoint in purinergic signaling on effector T cells. By depleting eATP and initiating the generation of adenosine, it impairs memory cell development and contributes to T cell exhaustion, thereby causing defective tumor immunity and deficient T cell responses in older adults who have increased CD39 expression. Tuning enzymatic activity of CD39 and targeting the transcriptional regulation of ENTPD1 can be used to modulate purinergic signaling. Here, we describe that STAT6 phosphorylation downstream of IL-4 signaling represses CD39 expression on activated T cells by inducing a transcription factor network including GATA3, GFI1, and YY1. GATA3 suppresses ENTPD1 transcription through prevention of RUNX3 recruitment to the ENTPD1 promoter. Conversely, pharmacological STAT6 inhibition decreases T cell effector functions via increased CD39 expression, resulting in the defective signaling of P2X receptors by ATP and stimulation of A2A receptors by adenosine. Our studies suggest that inhibiting the STAT6 pathway to increase CD39 expression has the potential to treat autoimmune disease while stimulation of the pathway could improve T cell immunity.

Self-degradable poly(ß-amino ester)s promote endosomal escape of antigen and agonist.

Vaccination with subunit nanovaccines is a promising strategy to combat virus infection and tumor development. However, immunogenicity of present nanovaccines is still unsatisfied for clinical translation. Here, we developed a nanovaccine loading a STING agonist, 2'3'-cGAMP and, a model subunit antigen, OVA, by using a well-defined self-degradable poly(ß-amino ester)s to treat B16F10-OVA melanoma tumors. The polymer underwent slow hydrolysis at pH 5.5 but self-degraded induced by the amino groups along the polyester chain at pH > 6.5. It is shown that the self-degradation products facilitated the release of 2'3'-cGAMP and OVA from early endolysome to the cytosol, where the two components strongly activated CD8+ T lymphocytes (CTLs) and significantly enhanced Ifn1, TNF, Cxcl9, and Cxcl10 expression. In turn, the tumor microenvironment was remolded from cold to hot. Moreover, the nanovaccine could be quickly drained to sentinel lymph nodes after intratumoral injection. The nanovaccine with strong immunogenicity also could reduce the side effects of systemic inflammatory reaction caused by molecular 2'3'-cGAMP. The tumor progression of animals was inhibited, and their survival rates increased significantly. Thus, the multifunctional biodegradable material provided a new delivery system for a cancer vaccine to translate to clinics.

Communication-Efficient and Collision-Free Motion Planning of Underwater Vehicles via Integral Reinforcement Learning.

Motion planning of underwater vehicles is regarded as a promising technique to make up the flexibility deficiency of underwater sensor networks (USNs). Nonetheless, the unique characteristics of underwater channel and environment make it challenging to achieve the above mission. This article is concerned with a communication-efficient and collision-free motion planning issue for underwater vehicles in fading channel and obstacle environment. We first develop a model-based integral reinforcement learning (IRL) estimator to predict the stochastic signal-to-noise ratio (SNR). With the estimated SNR, an integrated optimization problem for the codesign of communication efficiency and motion planning is constructed, in which the underwater vehicle dynamics, communication capacity, collision avoidance, and position control are all considered. In order to tackle this problem, a model-free IRL algorithm is designed to drive underwater vehicles to the desired position points while maximizing the communication capacity and avoiding the collision. It is worth mentioning that, the proposed motion planning solution in this article considers a realistic underwater communication channel, as well as a realistic dynamic model for underwater vehicles. Finally, simulation and experimental results are demonstrated to verify the effectiveness of the proposed approach.

The Characterization of Electronic Noise in the Charge Transport through Single-Molecule Junctions.

With the goal of creating single-molecule devices and integrating them into circuits, the emergence of single-molecule electronics provides various techniques for the fabrication of single-molecule junctions and the investigation of charge transport through such junctions. Among the techniques for characterization of charge transport through molecular junctions, electronic noise characterization is an effective strategy with which issues from molecule-electrode interfaces, mechanisms of charge transport, and changes in junction configurations are studied. Electronic noise analysis in single-molecule junctions can be used to identify molecular conformations and even monitor reaction kinetics. This review summarizes the various types of electronic noise that have been characterized during single-molecule electrical detection, including the functions of random telegraph signal (RTS) noise, flicker noise, shot noise, and their corresponding applications, which provide some guidelines for the future application of these techniques to problems of charge transport through single-molecule junctions.

The cell-surface 5'-nucleotidase CD73 defines a functional T memory cell subset that declines with age.

Memory T cells exhibit considerable diversity that determines their ability to be protective. Here, we examine whether changes in T cell heterogeneity contribute to the age-associated failure of immune memory. By screening for age-dependent T cell-surface markers, we identify CD4 and CD8 memory T cell subsets that are unrelated to previously defined subsets of central and effector memory cells. Memory T cells expressing the ecto-5'-nucleotidase CD73 constitute a functionally distinct subset of memory T cells that declines with age. They resemble long-lived, polyfunctional memory cells but are also poised to display effector functions and to develop into cells resembling tissue-resident memory T cells (TRMs). Upstream regulators of differential chromatin accessibility and transcriptomes include transcription factors that facilitate CD73 expression and regulate TRM differentiation. CD73 is not just a surrogate marker of these regulatory networks but is directly involved in T cell survival.