Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants.

The BQ and XBB subvariants of SARS-CoV-2 Omicron are now rapidly expanding, possibly due to altered antibody evasion properties deriving from their additional spike mutations. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly impaired, including sera from individuals boosted with a WA1/BA.5 bivalent mRNA vaccine. Titers against BQ and XBB subvariants were lower by 13- to 81-fold and 66- to 155-fold, respectively, far beyond what had been observed to date. Monoclonal antibodies capable of neutralizing the original Omicron variant were largely inactive against these new subvariants, and the responsible individual spike mutations were identified. These subvariants were found to have similar ACE2-binding affinities as their predecessors. Together, our findings indicate that BQ and XBB subvariants present serious threats to current COVID-19 vaccines, render inactive all authorized antibodies, and may have gained dominance in the population because of their advantage in evading antibodies.

Antigenicity and receptor affinity of SARS-CoV-2 BA.2.86 spike.

A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant, BA.2.86, has emerged and spread to numerous countries worldwide, raising alarm because its spike protein contains 34 additional mutations compared with its BA.2 predecessor1. We examined its antigenicity using human sera and monoclonal antibodies (mAbs). Reassuringly, BA.2.86 was no more resistant to human sera than the currently dominant XBB.1.5 and EG.5.1, indicating that the new subvariant would not have a growth advantage in this regard. Importantly, sera from people who had XBB breakthrough infection exhibited robust neutralizing activity against all viruses tested, suggesting that upcoming XBB.1.5 monovalent vaccines could confer added protection. Although BA.2.86 showed greater resistance to mAbs to subdomain 1 (SD1) and receptor-binding domain (RBD) class 2 and 3 epitopes, it was more sensitive to mAbs to class 1 and 4/1 epitopes in the 'inner face' of the RBD that is exposed only when this domain is in the 'up' position. We also identified six new spike mutations that mediate antibody resistance, including E554K that threatens SD1 mAbs in clinical development. The BA.2.86 spike also had a remarkably high receptor affinity. The ultimate trajectory of this new SARS-CoV-2 variant will soon be revealed by continuing surveillance, but its worldwide spread is worrisome.

Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2.

The B.1.1.529/Omicron variant of SARS-CoV-2 was only recently detected in southern Africa, but its subsequent spread has been extensive, both regionally and globally1. It is expected to become dominant in the coming weeks2, probably due to enhanced transmissibility. A striking feature of this variant is the large number of spike mutations3 that pose a threat to the efficacy of current COVID-19 vaccines and antibody therapies4. This concern is amplified by the findings of our study. Here we found that B.1.1.529 is markedly resistant to neutralization by serum not only from patients who recovered from COVID-19, but also from individuals who were vaccinated with one of the four widely used COVID-19 vaccines. Even serum from individuals who were vaccinated and received a booster dose of mRNA-based vaccines exhibited substantially diminished neutralizing activity against B.1.1.529. By evaluating a panel of monoclonal antibodies against all known epitope clusters on the spike protein, we noted that the activity of 17 out of the 19 antibodies tested were either abolished or impaired, including ones that are currently authorized or approved for use in patients. Moreover, we also identified four new spike mutations (S371L, N440K, G446S and Q493R) that confer greater antibody resistance on B.1.1.529. The Omicron variant presents a serious threat to many existing COVID-19 vaccines and therapies, compelling the development of new interventions that anticipate the evolutionary trajectory of SARS-CoV-2.

Antibody evasion properties of SARS-CoV-2 Omicron sublineages.

The identification of the Omicron (B.1.1.529.1 or BA.1) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Botswana in November 20211 immediately caused concern owing to the number of alterations in the spike glycoprotein that could lead to antibody evasion. We2 and others3-6 recently reported results confirming such a concern. Continuing surveillance of the evolution of Omicron has since revealed the rise in prevalence of two sublineages, BA.1 with an R346K alteration (BA.1+R346K, also known as BA.1.1) and B.1.1.529.2 (BA.2), with the latter containing 8 unique spike alterations and lacking 13 spike alterations found in BA.1. Here we extended our studies to include antigenic characterization of these new sublineages. Polyclonal sera from patients infected by wild-type SARS-CoV-2 or recipients of current mRNA vaccines showed a substantial loss in neutralizing activity against both BA.1+R346K and BA.2, with drops comparable to that already reported for BA.1 (refs. 2,3,5,6). These findings indicate that these three sublineages of Omicron are antigenically equidistant from the wild-type SARS-CoV-2 and thus similarly threaten the efficacies of current vaccines. BA.2 also exhibited marked resistance to 17 of 19 neutralizing monoclonal antibodies tested, including S309 (sotrovimab)7, which had retained appreciable activity against BA.1 and BA.1+R346K (refs. 2-4,6). This finding shows that no authorized monoclonal antibody therapy could adequately cover all sublineages of the Omicron variant, except for the recently authorized LY-CoV1404 (bebtelovimab).

Fast and efficient template-mediated synthesis of genetic variants.

Efficient methods for the generation of specific mutations enable the study of functional variations in natural populations and lead to advances in genetic engineering applications. Here, we present a new approach, mutagenesis by template-guided amplicon assembly (MEGAA), for the rapid construction of kilobase-sized DNA variants. With this method, many mutations can be generated at a time to a DNA template at more than 90% efficiency per target in a predictable manner. We devised a robust and iterative protocol for an open-source laboratory automation robot that enables desktop production and long-read sequencing validation of variants. Using this system, we demonstrated the construction of 31 natural SARS-CoV2 spike gene variants and 10 recoded Escherichia coli genome fragments, with each 4 kb region containing up to 150 mutations. Furthermore, 125 defined combinatorial adeno-associated virus-2 cap gene variants were easily built using the system, which exhibited viral packaging enhancements of up to 10-fold compared with wild type. Thus, the MEGAA platform enables generation of multi-site sequence variants quickly, cheaply, and in a scalable manner for diverse applications in biotechnology.

SMYD2-Methylated PPARγ Facilitates Hypoxia-Induced Pulmonary Hypertension by Activating Mitophagy.

BACKGROUND: Hyperproliferation of pulmonary arterial smooth muscle cells (PASMCs) and consequent pulmonary vascular remodeling are the crucial pathological features of pulmonary hypertension (PH). Protein methylation has been shown to be critically involved in PASMC proliferation and PH, but the underlying mechanism remains largely unknown. METHODS: PH animal models were generated by treating mice/rats with chronic hypoxia for 4 weeks. SMYD2-vTg mice (vascular smooth muscle cell-specific suppressor of variegation, enhancer of zeste, trithorax and myeloid Nervy DEAF-1 (deformed epidural auto-regulatory factor-1) domain-containing protein 2 transgenic) or wild-type rats and mice treated with LLY-507 (3-cyano-5-{2-[4-[2-(3-methylindol-1-yl)ethyl]piperazin-1-yl]-phenyl}-N-[(3-pyrrolidin-1-yl)propyl]benzamide) were used to investigate the function of SMYD2 (suppressor of variegation, enhancer of zeste, trithorax and myeloid Nervy DEAF-1 domain-containing protein 2) on PH development in vivo. Primary cultured rat PASMCs with SMYD2 knockdown or overexpression were used to explore the effects of SMYD2 on proliferation and to decipher the underlying mechanism. RESULTS: We demonstrated that the expression of the lysine methyltransferase SMYD2 was upregulated in the smooth muscle cells of pulmonary arteries from patients with PH and hypoxia-exposed rats/mice and in the cytoplasm of hypoxia-induced rat PASMCs. More importantly, targeted inhibition of SMYD2 by LLY-507 significantly attenuated hypoxia-induced pulmonary vascular remodeling and PH development in both male and female rats in vivo and reduced rat PASMC hyperproliferation in vitro. In contrast, SMYD2-vTg mice exhibited more severe PH phenotypes and related pathological changes than nontransgenic mice after 4 weeks of chronic hypoxia treatment. Furthermore, SMYD2 overexpression promoted, while SMYD2 knockdown suppressed, the proliferation of rat PASMCs by affecting the cell cycle checkpoint between S and G2 phases. Mechanistically, we revealed that SMYD2 directly interacted with and monomethylated PPARγ (peroxisome proliferator-activated receptor gamma) to inhibit the nuclear translocation and transcriptional activity of PPARγ, which further promoted mitophagy to facilitate PASMC proliferation and PH development. Furthermore, rosiglitazone, a PPARγ agonist, largely abolished the detrimental effects of SMYD2 overexpression on PASMC proliferation and PH. CONCLUSIONS: Our results demonstrated that SMYD2 monomethylates nonhistone PPARγ and inhibits its nuclear translocation and activation to accelerate PASMC proliferation and PH by triggering mitophagy, indicating that targeting SMYD2 or activating PPARγ are potential strategies for the prevention of PH.

DDX5 inhibits inflammation by modulating m6A levels of TLR2/4 transcripts during bacterial infection.

DExD/H-box helicases are crucial regulators of RNA metabolism and antiviral innate immune responses; however, their role in bacteria-induced inflammation remains unclear. Here, we report that DDX5 interacts with METTL3 and METTL14 to form an m6A writing complex, which adds N6-methyladenosine to transcripts of toll-like receptor (TLR) 2 and TLR4, promoting their decay via YTHDF2-mediated RNA degradation, resulting in reduced expression of TLR2/4. Upon bacterial infection, DDX5 is recruited to Hrd1 at the endoplasmic reticulum in an MyD88-dependent manner and is degraded by the ubiquitin-proteasome pathway. This process disrupts the DDX5 m6A writing complex and halts m6A modification as well as degradation of TLR2/4 mRNAs, thereby promoting the expression of TLR2 and TLR4 and downstream NF-κB activation. The role of DDX5 in regulating inflammation is also validated in vivo, as DDX5- and METTL3-KO mice exhibit enhanced expression of inflammatory cytokines. Our findings show that DDX5 acts as a molecular switch to regulate inflammation during bacterial infection and shed light on mechanisms of quiescent inflammation during homeostasis.

PDCD4 interacting with PIK3CB and CTSZ promotes the apoptosis of multiple myeloma cells.

The role of programmed cell death 4 (PDCD4) in multiple myeloma (MM) development remains unknown. Here, we investigated its role and action mechanism in MM. Bioinformatic analysis indicated that patients with MM and high PDCD4 expression had higher overall survival than those with low PDCD4 expression. PDCD4 expression promoted MM cell apoptosis and inhibited their viability in vitro and tumor growth in vivo. RNA-binding protein immunoprecipitation sequencing analysis showed that PDCD4 is bound to the 5' UTR of the apoptosis-related genes PIK3CB, Cathepsin Z (CTSZ), and X-chromosome-linked apoptosis inhibitor (XIAP). PDCD4 knockdown reduced the cell apoptosis rate, which was rescued by adding PIK3CB, CTSZ, or XIAP inhibitors. Dual luciferase reporter assays confirmed the internal ribosome entry site (IRES) activity of the 5' UTRs of PIK3CB and CTSZ. An RNA pull-down assay confirmed binding of the 5' UTR of PIK3CB and CTSZ to PDCD4, identifying the specific binding fragments. PDCD4 is expected to promote MM cell apoptosis by binding to the IRES domain in the 5' UTR of PIK3CB and CTSZ and inhibiting their translation. Our findings suggest that PDCD4 plays an important role in MM development by regulating the expression of PIK3CB, CTSZ, and XIAP, and highlight new potential molecular targets for MM treatment.

The mechanism by which cannabidiol (CBD) suppresses TNF-α secretion involves inappropriate localization of TNF-α converting enzyme (TACE).

Cannabidiol (CBD) is a phytocannabinoid derived from Cannabis sativa that exerts anti-inflammatory mechanisms. CBD is being examined for its putative effects on the neuroinflammatory disease, multiple sclerosis (MS). One of the major immune mediators that propagates MS and its mouse model experimental autoimmune encephalomyelitis (EAE) are macrophages. Macrophages can polarize into an inflammatory phenotype (M1) or an anti-inflammatory phenotype (M2a). Therefore, elucidating the impact on macrophage polarization with CBD pre-treatment is necessary to understand its anti-inflammatory mechanisms. To study this effect, murine macrophages (RAW 264.7) were pre-treated with CBD (10 µM) or vehicle (ethanol 0.1 %) and were either left untreated (naive; cell media only), or stimulated under M1 (IFN-γ + lipopolysaccharide, LPS) or M2a (IL-4) conditions for 24 hr. Cells were analyzed for macrophage polarization markers, and supernatants were analyzed for cytokines and chemokines. Immunofluorescence staining was performed on M1-polarized cells for the metalloprotease, tumor necrosis factor-α-converting enzyme (TACE), as this enzyme is responsible for the secretion of TNF-α. Overall results showed that CBD decreased several markers associated with the M1 phenotype while exhibiting less effects on the M2a phenotype. Significantly, under M1 conditions, CBD increased the percentage of intracellular and surface TNF-α but decreased secreted TNF-α. This phenomenon might be mediated by TACE as staining showed that CBD sequestered TACE intracellularly. CBD also prevented RelA nuclear translocation. These results suggest that CBD may exert its anti-inflammatory effects by reducing M1 polarization and decreasing TNF-α secretion via inappropriate localization of TACE and RelA.

Temperature-Dependent Electrochemical Performance of Ta-Substituted SrCoO3 Perovskite for Supercapacitors.

Developing new electrode materials with good temperature-dependent electrochemical performance has become a great issue for the deployment of hybrid supercapacitors with wide temperature tolerance. In this work, a series of Ta-substituted SrCo1-x Tax O3-δ (x=0.05, 0.10, 0.15, 0.20) perovskites have been studied as positive electrodes for hybrid supercapacitors in terms of their structures, elemental valence states and electrochemical performances. Incorporating Ta into SrCoO3-δ perovskite not only stabilizes the crystallite structure but also notably improves electrochemical activities. The SrCo0.95 Ta0.05 O3-δ @CC delivers the highest specific capacity (Qsp ) of 227.91 C g-1 at 1 A g-1 , which is attributed to the highest oxygen vacancy content and the fastest oxygen diffusion kinetics. The hybrid supercapacitor SrCo0.95 Ta0.05 O3-δ @CC//AC@CC exhibits a high energy density of 22.82 Wh kg-1 @775.09 W kg-1 and a stable long-term cycle life (5000 cycles) with 90.7 % capacity retention. As temperature increases from 25 to 85 °C, the capacitance properties are improved at elevated temperatures for both electrode and device due to the increased electrolyte conductivity. The outstanding electrochemical results present that SrCo1-x Tax O3-δ perovskite holds good prospects for hybrid supercapacitors with wide temperature tolerance.

Repetitive transcranial magnetic stimulation ameliorates cognitive deficits in mice with radiation-induced brain injury by attenuating microglial pyroptosis and promoting neurogenesis via BDNF pathway.

BACKGROUND: Radiation-induced brain injury (RIBI) is a common and severe complication during radiotherapy for head and neck tumor. Repetitive transcranial magnetic stimulation (rTMS) is a novel and non-invasive method of brain stimulation, which has been applied in various neurological diseases. rTMS has been proved to be effective for treatment of RIBI, while its mechanisms have not been well understood. METHODS: RIBI mouse model was established by cranial irradiation, K252a was daily injected intraperitoneally to block BDNF pathway. Immunofluorescence staining, immunohistochemistry and western blotting were performed to examine the microglial pyroptosis and hippocampal neurogenesis. Behavioral tests were used to assess the cognitive function and emotionality of mice. Golgi staining was applied to observe the structure of dendritic spine in hippocampus. RESULTS: rTMS significantly promoted hippocampal neurogenesis and mitigated neuroinflammation, with ameliorating pyroptosis in microglia, as well as downregulation of the protein expression level of NLRP3 inflammasome and key pyroptosis factor Gasdermin D (GSDMD). BDNF signaling pathway might be involved in it. After blocking BDNF pathway by K252a, a specific BDNF pathway inhibitor, the neuroprotective effect of rTMS was markedly reversed. Evaluated by behavioral tests, the cognitive dysfunction and anxiety-like behavior were found aggravated with the comparison of mice in rTMS intervention group. Moreover, the level of hippocampal neurogenesis was found to be attenuated, the pyroptosis of microglia as well as the levels of GSDMD, NLRP3 inflammasome and IL-1ß were upregulated. CONCLUSION: Our study indicated that rTMS notably ameliorated RIBI-induced cognitive disorders, by mitigating pyroptosis in microglia and promoting hippocampal neurogenesis via mediating BDNF pathway.

From Gatekeeper to Facilitator: Balancing Between Sexual Rights and Protection From Harm in Dementia Adults.

OBJECTIVE: The assessment of sexual consent capacity has been a challenge due to its dynamic nature, influenced by factors such as time, environment, individuals involved, and the nature of activities. Particularly in people living with dementia, the complexity is intensified with the interplay of the disease's impact, residential care setting, and legal constraints. This amplifies the dilemma faced by practitioners-whether to prioritize protection or encourage and support sexual expression. This article aims to provide a sensible approach to uphold the sexual autonomy of people living with dementia while mitigating the potential risks of them being involved as either perpetrators or victims. METHODS: In this narrative review, a literature search spanning from 1990 to 2023 was carried out on PubMed. Relevant articles on people living with dementia and topics related to sexuality were scrutinized. RESULTS: 41 relevant articles identified themes related to the impact of cognitive impairment on sexuality, challenges in residential care facilities, sexual consent capacity assessment models, and ethical frameworks regarding sexual rights and law. CONCLUSION: Discussions highlight the often neglected influence of prolonged suppression of sexual expression and the benefits of actualization of sexual autonomy, especially in people living with dementia, whose sense of identity is fading. It scrutinizes the limitations of existing sexual consent capacity evaluation models, emphasizing ethical concerns, practical challenges, and the need for a more balanced approach. Proposed strategies advocate for a shift from a gatekeeper to a facilitator role, offering principles for setting educational programs and policies to mitigate obstacles, supporting sexual rights, and safeguarding vulnerable groups.

Fungi play a crucial role in sustaining microbial networks and accelerating organic matter mineralization and humification during thermophilic phase of composting.

Fungi play an important role in the mineralization and humification of refractory organic matter such as lignocellulose during composting. However, limited research on the ecological role of fungi in composting system hindered the development of efficient microbial agents. In this study, six groups of lab-scale composting experiments were conducted to reveal the role of fungal community in composting ecosystems by comparing them with bacterial community. The findings showed that the thermophilic phase was crucial for organic matter degradation and humic acid formation. The Richness index of the fungal community peaked at 1165 during this phase. PCoA analysis revealed a robust thermal stability in the fungal community. Despite temperature fluctuations, the community structure, predominantly governed by Pichia and Candida, remained largely unaltered. The stability of fungal community and the complexity of ecological networks were 1.26 times and 5.15 times higher than those observed in bacterial community, respectively. Fungi-bacteria interdomain interaction markedly enhanced network complexity, contributing to maintain microbial ecological functions. The core fungal species belonging to the family Saccharomycetaceae drove interdomain interaction during thermophilic phase. This study demonstrated the key role of fungi in the composting system, which would provide theoretical guidance for the development of high efficiency composting agents to strengthen the mineralization and humification of organic matter.

Heavy metal pollution near an abandoned mercury-bearing waste recovery enterprise in southwestern China: Spatial distribution and its sources in soil and plants.

The contribution of smelting of nonferrous metals to heavy metals in surface soil have become increasingly important over the past decade. In this study, the distribution of heavy metals around an abandoned mercury-bearing waste recovery enterprise were investigated. Soil (14) and plant (18) samples were collected in the surrounding area. The total concentration of heavy metals and methyl mercury content were measured by ICP-MS and HPLC-ICP-MS. The results show that the average contents of Cd, Cr, Pb, Hg and As in all soil samples are higher than the second-level values of Soil environmental quality-Risk control standard for soil contamination of development land (GB 36600-2018). Hg in the leaves ranged from 0.003 to 0.174 mg kg-1. Besides, the Pearson correlation analysis results indicate that Hg has a different environmental behavior compared to the other heavy metal under certain environmental or geographical conditions. But the mantel test statistical analysis results show that the Cr (P < 0.01), Cu, Pb, and Fe (P < 0.05) in the soil may have similar pollution sources with carbonate-bound mercury and iron-manganese oxide-bound mercury. The Hg concentrations show no correlation among plant leaves and soil, but significantly influenced by the distance and wind direction. These findings suggest that Hg in plant leaves may be derived from the deposition of atmospheric mercury from secondary mercury plant. The results will supplement those for relevant policy making for mercury-bearing waste recovery enterprises to improve urban environmental quality and human health.

Rural revival: Navigating environmental engineering and technology.

The necessity for global engineering and technological solutions to address rural environmental challenges is paramount, particularly in improving rural waste treatment and infrastructure. This study presents a comprehensive quantitative analysis of 3901 SCI/SSCI and 3818 Chinese CSCD papers, spanning from 1989 to 2021, using tools like Derwent Data Analyzer and VOSviewer. Our key findings reveal a significant evolution in research focus, including a 716.67% increase in global publications from 1995 to 2008 and a 154.76% surge from 2015 to 2021, highlighting a growing research interest with technological hotspots in rural revitalization engineering and agricultural waste recycling. China and the USA are pivotal, contributing 784 and 714 publications respectively. Prominent institutions such as the Chinese Academy of Sciences play a crucial role, particularly in fecal waste treatment technology. These insights advocate for enhanced policy development and practical implementations to foster inclusive and sustainable rural environments globally.

Terahertz fingerprint reveals the effect of alcohols on sodium ions hydration shell.

Ion hydration plays a crucial role in numerous fundamental processes. Various spectroscopic methods are employed to investigate the slowing down of hydration bond dynamics in the proximity of both anions and cations. To date, most of these studies have primarily focused on the properties of binary systems. However, in comparison to ion-water binary systems, ternary systems that involve ions, water, and organic matter are more prevalent in nature and provide more realistic insights into biological processes. This study focuses on ion hydration in water and alcohol mixture using terahertz spectroscopy and x-ray diffraction (XRD). The results reveal a distinct behavior depending on the type of alcohol used. Specifically, the presence of both methanol and ethanol results in the disappearance of absorption peaks associated with NaCl hydrate at low temperatures. In contrast, tert-butanol does not exhibit such an effect, and isopropanol demonstrates a more complex response. By combining these terahertz spectroscopic findings with low-temperature XRD data, we gain insights into the formation, or lack thereof, of NaCl · 2H2O hydrate crystals. Crucially, our observations suggest a dominant correlation between the polarity of the alcohol molecules and its impact on the Na+ hydration. Strongly polar alcohols preferentially solvating the Na+ ion lead to the failure of hydrate formation, while weakly polar alcohols do not have this effect.

Metabolomic differences between exanthematous drug eruption and infectious mononucleosis.

BACKGROUND: Exanthematous drug eruption and infectious mononucleosis (IM) are both exanthematous diseases. Current research on exanthematous drug eruption and IM mainly targets identifying these disorders, the resulting differences at the metabolism level have not yet been systematically analyzed. MATERIALS AND METHODS: A total of 30 cases of exanthematous drug eruption and IM, 10 patients without exanthema and 10 healthy volunteers were enrolled, 3 mL of fasting venous blood was collected, the serum metabolite content was detected by gas chromatography-mass spectrometry metabolomics. RESULTS: A total of 165 metabolites were identified, exhibiting significant differences in plasma metabolic trends between exanthematous drug eruption and IM, and pinpointed 28 potential biomarkers. Notable changes were seen in the metabolic activities of the pentose phosphate pathway (PPP), tricarboxylic acid cycle (TCA-cycle), and galactose metabolism, characterized by increased levels of gluconate, gluconolactone, glucose, galactaric acid, and mannose, along with decreased amounts of pyruvic acid, succinic acid, malic acid, and glycerol, indicating an impairment in the exanthematous drug eruption group's capacity to endure oxidative stress and regulate energy metabolism. In contrast to its medication without rash counterpart, the exanthematous drug eruption group's plasma displayed distinct metabolic routes, predominantly in the processing of arginine and proline, along with the TCA. This resulted in a marked reduction in urea levels and a rise in pyruvate, citrate, and ornithine, indicating hypoxic stress as the primary cause of these rashes. In contrast to the healthy control group, the IM group showed 26 potential biomarkers, marked by increased levels of ketoglutaric acid, malic acid, pyruvic acid, and oxoglutaric acid, and reduced amounts of glutamine, galacturonic acid, arachidonic acid, trimethylphosphonic acid ester, gluconolactone, and indole acetic acid. Mainly, the metabolic pathways included the TCA, breaking down alanine, aspartate and glutamate metabolism, and the processing of D-glutamine and D-glutamate metabolism, underscoring the body's crucial role in generating energy and inflammatory agents through the citric acid cycle. CONCLUSIONS: The comparison of serum metabolomic features of exanthematous drug eruptions and IM outlines a unique pattern closely related to the differences in the pathogenesis of these two exanthematous diseases.

SCF/C-kit drives spermatogenesis disorder induced by abscopal effects of cranial irradiation in mice.

Cranial radiotherapy is a major treatment for leukemia and brain tumors. Our previous study found abscopal effects of cranial irradiation could cause spermatogenesis disorder in mice. However, the exact mechanisms are not yet fully understood. In the study, adult male C57BL/6 mice were administrated with 20 Gy X-ray cranial irradiation (5 Gy per day for 4 days consecutively) and sacrificed at 1, 2 and 4 weeks. Tandem Mass Tag (TMT) quantitative proteomics of testis was combined with bioinformatics analysis to identify key molecules and signal pathways related to spermatogenesis at 4 weeks after cranial irradiation. GO analysis showed that spermatogenesis was closely related to oxidative stress and inflammation. Severe oxidative stress occurred in testis, serum and brain, while serious inflammation also occurred in testis and serum. Additionally, the sex hormones related to hypothalamic-pituitary-gonadal (HPG) axis were disrupted. PI3K/Akt pathway was activated in testis, which upstream molecule SCF/C-Kit was significantly elevated. Furthermore, the proliferation and differentiation ability of spermatogonial stem cells (SSCs) were altered. These findings suggest that cranial irradiation can cause spermatogenesis disorder through brain-blood-testicular cascade oxidative stress, inflammation and the secretory dysfunction of HPG axis, and SCF/C-kit drive this process through activating PI3K/Akt pathway.

A 64 × 128 3D-Stacked SPAD Image Sensor for Low-Light Imaging.

Low-light imaging capabilities are in urgent demand in many fields, such as security surveillance, night-time autonomous driving, wilderness rescue, and environmental monitoring. The excellent performance of SPAD devices gives them significant potential for applications in low-light imaging. This article presents a 64 (rows) × 128 (columns) SPAD image sensor designed for low-light imaging. The chip utilizes a three-dimensional stacking architecture and microlens technology, combined with compact gated pixel circuits designed with thick-gate MOS transistors, which further enhance the SPAD's photosensitivity. The configurable digital control circuit allows for the adjustment of exposure time, enabling the sensor to adapt to different lighting conditions. The chip exhibits very low dark noise levels, with an average DCR of 41.5 cps at 2.4 V excess bias voltage. Additionally, it employs a denoising algorithm specifically developed for the SPAD image sensor, achieving two-dimensional grayscale imaging under 6 × 10-4 lux illumination conditions, demonstrating excellent low-light imaging capabilities. The chip designed in this paper fully leverages the performance advantages of SPAD image sensors and holds promise for applications in various fields requiring low-light imaging capabilities.

The effects of different interruption conditions on mental workload: an experimental study based on multimodal measurements.

Interruptions in the working environment cause extra mental workload for the operators, and this phenomenon has garnered significant research attention. This study designed four interruption conditions based on the perceptual and cognitive perspectives of human information processing, using a 2(perceptual primary task and cognitive primary task)*2(perceptual interruption task and cognitive interruption task) factorial design. Multimodal measurement methods were used to evaluate mental workload in different interruption conditions. The results show that when the primary task and the interruption task are different load types, they generate a higher mental workload than the same load type. It can be attributed to the fact that perceptual tasks and cognitive tasks increase mental workload during switching. In addition, based on the multimodal index data, the prediction model of interruption recovery delay time and the classification model of interruption conditions are established, which provides a basis for rational scheduling of work and preventing mental overload.

This study's results enhance our understanding of interruptions from the perspectives of perception and cognition, providing a more accurate theoretical basis for managing mental workload in interruption conditions. The proposed interruption recovery delay time prediction model and the interruption condition classification model have certain reference values for improving interruption management capabilities.