Sub-THz High Spin Precession Frequency in van der Waals Ferromagnet Fe3GaTe2.

The 2D magnet Fe3GaTe2 has received considerable attention for its high Curie temperature (TC), robust intrinsic ferromagnetism, and significant perpendicular magnetic anisotropy (PMA). In this study, the dynamic magnetic properties of Fe3GaTe2 are systematically investigated using an all-optical pump-probe technique. We find that the spin precession frequency (f) is as high as 351.2 GHz at T = 10 K under a field of H = 70 kOe. However, it decreases to 242.8 GHz at 300 K, mainly due to the reduced effective PMA field (Hkeff). The Gilbert damping factor (α) is modest, which increases from 0.039 (10 K) to 0.075 (300 K) owing to the enhanced scattering rate. Interestingly, when Fe3GaTe2 is coupled with 2 nm of Co, the Hkeff, f, and α just decrease slightly, highlighting the dominant influence of Fe3GaTe2. These findings substantially deepen our understanding of Fe3GaTe2, promoting the development of spintronic devices based on advanced 2D magnetic materials.

African swine fever virus pS273R antagonizes stress granule formation by cleaving the nucleating protein G3BP1 to facilitate viral replication.

Cytoplasmic stress granules (SGs) are generally triggered by stress-induced translation arrest for storing mRNAs. Recently, it has been shown that SGs are regulated by different stimulators including viral infection, which is involved in the antiviral activity of host cells to limit viral propagation. To survive, several viruses have been reported to execute various strategies, such as modulating SG formation, to create optimal surroundings for viral replication. African swine fever virus (ASFV) is one of the most notorious pathogens in the global pig industry. However, the interplay between ASFV infection and SG formation remains largely unknown. In this study, we found that ASFV infection inhibited SG formation. Through SG inhibitory screening, we found that several ASFV-encoded proteins are involved in inhibition of SG formation. Among them, an ASFV S273R protein (pS273R), the only cysteine protease encoded by the ASFV genome, significantly affected SG formation. ASFV pS273R interacted with G3BP1 (Ras-GTPase-activating protein [SH3 domain] binding protein 1), a vital nucleating protein of SG formation. Furthermore, we found that ASFV pS273R cleaved G3BP1 at the G140-F141 to produce two fragments (G3BP1-N1-140 and G3BP1-C141-456). Interestingly, both the pS273R-cleaved fragments of G3BP1 lost the ability to induce SG formation and antiviral activity. Taken together, our finding reveals that the proteolytic cleavage of G3BP1 by ASFV pS273R is a novel mechanism by which ASFV counteracts host stress and innate antiviral responses.

Glucose metabolism in glioma: an emerging sight with ncRNAs.

Glioma is a primary brain tumor that grows quickly, has an unfavorable prognosis, and can spread intracerebrally. Glioma cells rely on glucose as the major energy source, and glycolysis plays a critical role in tumorigenesis and progression. Substrate utilization shifts throughout glioma progression to facilitate energy generation and biomass accumulation. This metabolic reprogramming promotes glioma cell proliferation and metastasis and ultimately decreases the efficacy of conventional treatments. Non-coding RNAs (ncRNAs) are involved in several glucose metabolism pathways during tumor initiation and progression. These RNAs influence cell viability and glucose metabolism by modulating the expression of key genes of the glycolytic pathway. They can directly or indirectly affect glycolysis in glioma cells by influencing the transcription and post-transcriptional regulation of oncogenes and suppressor genes. In this review, we discussed the role of ncRNAs in the metabolic reprogramming of glioma cells and tumor microenvironments and their abnormal expression in the glucometabolic pathway in glioma. In addition, we consolidated the existing theoretical knowledge to facilitate the use of this emerging class of biomarkers as biological indicators and potential therapeutic targets for glioma.

Differential effects of sleep deprivation on behavior and microglia in a brain-region-specific manner in young and aged male mice.

Microglia, resident immune cells in the central nervous system, constantly monitor the state of the surrounding brain activity. The animal model induced by sleep deprivation (SD) is widely used to study the pathophysiological mechanisms of insomnia and bipolar disorder. However, it remains unclear whether SD affects behaviors in young and aged male mice and microglia in various brain regions. In this study, we confirmed brain region-specific changes in microglial density and morphology in the accumbens nucleus (Acb), amygdala (AMY), cerebellum (Cb), corpus callosum (cc), caudate putamen, hippocampus (HIP), hypothalamus (HYP), medial prefrontal cortex (mPFC), and thalamus (TH) of young mice. In addition, the density of microglia in old mice was higher than that in young mice. Compared with young mice, old mice showed a markedly increased microglial size, decreased total length of microglial processes, and decreased maximum length. Importantly, we found that 48-h SD decreased microglial density and morphology in old mice, whereas SD increased microglial density and morphology in most observed brain regions in young mice. SD-induced hyperactivity was observed only in young mice but not in old mice. Moreover, microglial density (HIP, AMY, mPFC, CPu) was significantly positively correlated with behaviors in SD- and vehicle-treated young mice. Contrarily, negative correlations were shown between the microglial density (cc, Cb, TH, HYP, Acb, AMY) and behaviors in vehicle-treated young and old mice. These results suggest that SD dysregulates the homeostatic state of microglia in a region- and age-dependent manner. Microglia may be involved in regulating age-related behavioral responses to SD.

From zinc homeostasis to disease progression: Unveiling the neurodegenerative puzzle.

Zinc is a crucial trace element in the human body, playing a role in various physiological processes such as oxidative stress, neurotransmission, protein synthesis, and DNA repair. The zinc transporters (ZnTs) family members are responsible for exporting intracellular zinc, while Zrt- and Irt-like proteins (ZIPs) are involved in importing extracellular zinc. These processes are essential for maintaining cellular zinc homeostasis. Imbalances in zinc metabolism have been linked to the development of neurodegenerative diseases. Disruptions in zinc levels can impact the survival and activity of neurons, thereby contributing to the progression of neurodegenerative diseases through mechanisms like cell apoptosis regulation, protein phase separation, ferroptosis, oxidative stress, and neuroinflammation. Therefore, conducting a systematic review of the regulatory network of zinc and investigating the relationship between zinc dysmetabolism and neurodegenerative diseases can enhance our understanding of the pathogenesis of these diseases. Additionally, it may offer new insights and approaches for the treatment of neurodegenerative diseases.

Astrocyte-derived lactoferrin inhibits neuronal ferroptosis by reducing iron content and GPX4 degradation in APP/PS1 transgenic mice.

Increased astrocytic lactoferrin (Lf) expression was observed in the brains of elderly individuals and Alzheimer's disease (AD) patients. Our previous study revealed that astrocytic Lf overexpression improved cognitive capacity by facilitating Lf secretion to neurons to inhibit ß-amyloid protein (Aß) production in APP/PS1 mice. Here, we further discovered that astrocytic Lf overexpression inhibited neuronal loss by decreasing iron accumulation and increasing glutathione peroxidase 4 (GPX4) expression in neurons within APP/PS1 mice. Furthermore, human Lf (hLf) treatment inhibited ammonium ferric citrate (FAC)-induced ferroptosis by chelating intracellular iron. Additionally, machine learning analysis uncovered a correlation between Lf and GPX4. hLf treatment boosted low-density lipoprotein receptor-related protein 1 (LRP1) internalization and facilitated its interaction with heat shock cognate 70 (HSC70), thereby inhibiting HSC70 binds to GPX4, and eventually attenuating GPX4 degradation and FAC-induced ferroptosis. Overall, astrocytic Lf overexpression inhibited neuronal ferroptosis through two pathways: reducing intracellular iron accumulation and promoting GPX4 expression via inhibiting chaperone-mediated autophagy (CMA)-mediated GPX4 degradation. Hence, upregulating astrocytic Lf expression is a promising strategy for combating AD.

Signal enhancement ratio of multi-phase contrast-enhanced MRI: an imaging biomarker for survival in pancreatic adenocarcinoma.

OBJECTIVES: To evaluate signal enhancement ratio (SER) for tissue characterization and prognosis stratification in pancreatic adenocarcinoma (PDAC), with quantitative histopathological analysis (QHA) as the reference standard. METHODS: This retrospective study included 277 PDAC patients who underwent multi-phase contrast-enhanced (CE) MRI and whole-slide imaging (WSI) from three centers (2015-2021). SER is defined as (SIlt - SIpre)/(SIea - SIpre), where SIpre, SIea, and SIlt represent the signal intensity of the tumor in pre-contrast, early-, and late post-contrast images, respectively. Deep-learning algorithms were implemented to quantify the stroma, epithelium, and lumen of PDAC on WSIs. Correlation, regression, and Bland-Altman analyses were utilized to investigate the associations between SER and QHA. The prognostic significance of SER on overall survival (OS) was evaluated using Cox regression analysis and Kaplan-Meier curves. RESULTS: The internal dataset comprised 159 patients, which was further divided into training, validation, and internal test datasets (n = 60, 41, and 58, respectively). Sixty-five and 53 patients were included in two external test datasets. Excluding lumen, SER demonstrated significant correlations with stroma (r = 0.29-0.74, all p < 0.001) and epithelium (r = -0.23 to -0.71, all p < 0.001) across a wide post-injection time window (range, 25-300 s). Bland-Altman analysis revealed a small bias between SER and QHA for quantifying stroma/epithelium in individual training, validation (all within ± 2%), and three test datasets (all within ± 4%). Moreover, SER-predicted low stromal proportion was independently associated with worse OS (HR = 1.84 (1.17-2.91), p = 0.009) in training and validation datasets, which remained significant across three combined test datasets (HR = 1.73 (1.25-2.41), p = 0.001). CONCLUSION: SER of multi-phase CE-MRI allows for tissue characterization and prognosis stratification in PDAC. CLINICAL RELEVANCE STATEMENT: The signal enhancement ratio of multi-phase CE-MRI can serve as a novel imaging biomarker for characterizing tissue composition and holds the potential for improving patient stratification and therapy in PDAC. KEY POINTS: Imaging biomarkers are needed to better characterize tumor tissue in pancreatic adenocarcinoma. Signal enhancement ratio (SER)-predicted stromal/epithelial proportion showed good agreement with histopathology measurements across three distinct centers. Signal enhancement ratio (SER)-predicted stromal proportion was demonstrated to be an independent prognostic factor for OS in PDAC.

Tunable Emission of Low-Dimensional Organic Metal Halides by Stoichiometric Ratio and Metal Center.

Low-dimensional (LD) organic metal halides (OMHs) have a bright future due to their excellent photoelectric characteristics and unique structure. However, the synthesis and emission control of LD-OMHs are still unclear. Herein, the different dimensional (zero-dimensional (0D), one-dimensional (1D), and three-dimensional (3D)) of OMHs were obtained by the reaction of 1,4-diazabicyclo (2.2.2) octane with PbBr2 in different stoichiometric ratios. This discovery shows that the structure and properties of OMHs can be regulated while maintaining the functional organic cations of OMHs, which broadens the path for the development of functional LD-OMHs. Among them, 0D-OMH 1 and 1D-OMH 3 have narrow-band (full width at half-maximum (fwhm) = 74 nm) and broad-band (fwhm = 201 nm) emission, respectively. We found that when organic cations have no contribution to the formation of conduction band minimum and valence band maximum, and the distances between polyhedrons are larger than the van der Waals diameter of the halogen atom, the effect of phonons on exciton transitions can be reduced to achieve a narrow-band emission. Further, Cu(I)- and Mn (II)-based 0D-OMHs were synthesized, which have high photoluminescence quantum yield (PLQY) (33.97 and 47.33%, respectively). When the emitting of 0D-OMHs produced by the interaction of the metal-center and halogens, the asymmetric planar metal-halogen structure will result in a higher PLQY.

Anthropogenic disturbance driving population decline of a dominant tree in East Asia evergreen broadleaved forests over the last 11,000 years.

Current biodiversity loss is generally considered to have been caused by anthropogenic disturbance, but it is unclear when anthropogenic activities began to affect biodiversity loss. One hypothesis suggests it began with the Industrial Revolution, whereas others propose that anthropogenic disturbance has been associated with biodiversity decline since the early Holocene. To test these hypotheses, we examined the unique vegetation of evergreen broadleaved forests (EBLFs) in East Asia, where humans have affected landscapes since the early Holocene. We adopted a genomic approach to infer the demographic history of a dominant tree (Litsea elongata) of EBLFs. We used Holocene temperature and anthropogenic disturbance factors to calculate the correlation between these variables and the historical effective population size of L. elongata with Spearman statistics and integrated the maximum-entropy niche model to determine the impact of climate change and anthropogenic disturbance on fluctuation in its effective population size. We identified 9 well-defined geographic clades for the populations of L. elongata. Based on the estimated historical population sizes of these clades, all the populations contracted, indicating persistent population decline over the last 11,000 years. Demographic history of L. elongata and human population change, change in cropland use, and change in irrigated rice area were significantly negatively correlated, whereas climate change in the Holocene was not correlated with demographic history. Our results support the early human impact hypothesis and provide comprehensive evidence that early anthropogenic disturbance may contribute to the current biodiversity crisis in East Asia.

Methane Production Is More Sensitive to Temperature Increase than Aerobic and Anaerobic Methane Oxidation in Chinese Paddy Soils.

Methane emissions from paddy fields can increase under future warming scenarios. Nevertheless, a comprehensive comparison of the temperature sensitivity of methane-related microbial processes remains elusive. Here, we revealed that the temperature sensitivity of methane production (activation energy (Ea) = 0.94 eV; 95% confidence interval (CI), 0.78-1.10 eV) and aerobic (Ea = 0.49 eV; 95% CI, 0.34-0.65 eV) and anaerobic (Ea = 0.46 eV; 95% CI, 0.30-0.62 eV) methane oxidation exhibited notable spatial heterogeneity across 12 Chinese paddy fields spanning 35° longitude and 18° latitude. In addition, the Ea values of aerobic and anaerobic methane oxidation were significantly positively and negatively correlated to the latitude, respectively, while there was no significant correlation between the Ea of methane production and the latitude. Overall, there were no soil factors that had a significant effect on the Ea of methane production. The Ea of aerobic methane oxidation was primarily influenced by the contents of ammonium and clay, whereas the Ea of anaerobic methane oxidation was mainly influenced by the conductivity. Despite the variation, the overall temperature sensitivity of methane production was significantly higher than that of oxidation at a continental scale; therefore, an increase in the emission of methane from paddy fields will be predicted under future warming. Taken together, our study revealed the characteristics of temperature sensitivity of methane production and aerobic and anaerobic methane oxidation simultaneously in Chinese paddy fields, highlighting the potential roles of soil factors in influencing temperature sensitivity.

Identification and analysis of MAPK cascade gene families of Camellia oleifera and their roles in response to cold stress.

BACKGROUND: Low-temperature severely limits the growth and development of Camellia oleifera (C. oleifera). The mitogen-activated protein kinase (MAPK) cascade plays a key role in the response to cold stress. METHODS AND RESULTS: Our study aims to identify MAPK cascade genes in C. oleifera and reveal their roles in response to cold stress. In our study, we systematically identified and analyzed the MAPK cascade gene families of C. oleifera, including their physical and chemical properties, conserved motifs, and multiple sequence alignments. In addition, we characterized the interacting networks of MAPKK kinase (MAPKKK)-MAPK kinase (MAPKK)-MAPK in C. oleifera. The molecular mechanism of cold stress resistance of MAPK cascade genes in wild C. oleifera was analyzed by differential gene expression and real-time quantitative reverse transcription-PCR (qRT-PCR). CONCLUSION: In this study, 21 MAPKs, 4 MAPKKs and 55 MAPKKKs genes were identified in the leaf transcriptome of C. oleifera. According to the phylogenetic results, MAPKs were divided into 4 groups (A, B, C and D), MAPKKs were divided into 3 groups (A, B and D), and MAPKKKs were divided into 2 groups (MEKK and Raf). Motif analysis showed that the motifs in each subfamily were conserved, and most of the motifs in the same subfamily were basically the same. The protein interaction network based on Arabidopsis thaliana (A. thaliana) homologs revealed that MAPK, MAPKK, and MAPKKK genes were widely involved in C. oleifera growth and development and in responses to biotic and abiotic stresses. Gene expression analysis revealed that the CoMAPKKK5/CoMAPKKK43/CoMAPKKK49-CoMAPKK4-CoMAPK8 module may play a key role in the cold stress resistance of wild C. oleifera at a high-elevation site in Lu Mountain (LSG). This study can facilitate the mining and utilization of genetic resources of C. oleifera with low-temperature tolerance.

Robust and orange-yellow-emitting Sr-rich polytypoid α-SiAlON (Sr3Si24Al6N40:Eu2+) phosphor for white LEDs.

Nitrides and oxynitrides isostructural to α-Si3N4 (M-α-SiAlON, M = Sr, Ca, Li) possess superb thermally stable photoluminescence (PL) properties, making them reliable phosphors for high-power solid-state lighting. However, the synthesis of phase-pure Sr-α-SiAlON still remains a great challenge and has only been reported for Sr below 1.35 at.% as the large size of Sr2+ ions tends to destabilize the α-SiAlON structure. Here, we succeeded to synthesize the single-phase powders of a unique 'Sr-rich' polytypoid α-SiAlON (Sr3Si24Al6N40:Eu2+) phosphor with three distinctive Sr/Eu luminescence sites using a solid-state remixing-reannealing process. The Sr content of this polytypoid structure exceeds those of a few previously reported structures by over 200%. The phase purity, composition, structure, and PL properties of this phosphor were investigated. A single phase can be obtained by firing the stoichiometric mixtures of all-nitride precursors at 2050°C under a 0.92 MPa N2 atmosphere. The Sr3Si24Al6N40:Eu2+ shows an intense orange-yellow emission, with the emission maximum of 590 nm and internal/external quantum efficiency of 66%/52% under 400 nm excitation. It also has a quite small thermal quenching, maintaining 93% emission intensity at 150°C. In comparison to Ca-α-SiAlON:Eu2+, this Sr counterpart shows superior quantum efficiency and thermal stability, enabling it to be an interesting orange-yellow down-conversion luminescent material for white LEDs. The experimental confirmation of the existence of such 'Sr-rich' SiAlON systems, in a single-phase powder form, paves the way for the design and synthesis of novel 'Sr-rich' SiAlON-based phosphor powders with unparalleled properties.

A distinctive orange-yellow-emitting 'Sr-rich' α-SiAlON-based phosphor with quite small thermal quenching (93% PL intensity at 150°C) that can surprisingly be synthesized in a single-phase powder form for white LEDs.

Genome-Wide Identification and Role of the bHLH Gene Family in Dendrocalamus latiflorus Flowering Regulation.

The basic helix-loop-helix (bHLH) gene family is a crucial regulator in plants, orchestrating various developmental processes, particularly flower formation, and mediating responses to hormonal signals. The molecular mechanism of bamboo flowering regulation remains unresolved, limiting bamboo breeding efforts. In this study, we identified 309 bHLH genes and divided them into 23 subfamilies. Structural analysis revealed that proteins in specific DlbHLH subfamilies are highly conserved. Collinearity analysis indicates that the amplification of the DlbHLH gene family primarily occurs through segmental duplications. The structural diversity of these duplicated genes may account for their functional variability. Many DlbHLHs are expressed during flower development, indicating the bHLH gene's significant role in this process. In the promoter region of DlbHLHs, different homeopathic elements involved in light response and hormone response co-exist, indicating that DlbHLHs are related to the regulation of the flower development of D. latiflorus.

Optimization of lyoprotectant for recombinant human acidic fibroblast growth factor by response surface methodology.

Recombinant human acidic fibroblast growth factor (rh-aFGF) is a widely used biological product, but it is unstable and its biological activity is easy to decrease. In order to maintain the long-term stability and biological activity of rh-aFGF, based on the response surface method, the freeze-drying characterization and cell proliferation rate of rh-aFGF freeze-dried powder were evaluated by scoring and Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay in this study. The optimal concentrations of trehalose, glycine and BSA were optimized, and the optimal formulation was verified by regression experiment. The results showed that trehalose, glycine and BSA had significant effects on the characterization of lyophilized rh-aFGF and cell proliferation. The optimal formulation of 5.7% trehalose, 2.04% glycine and 1.98%BSA combined with rh-aFGF could achieve the optimal freeze-dried characterization and biological activity. Using the best formulation to verify, the freeze-dried formability index of the freeze-dried powder was 23.35, and the rate of cell proliferation was 43.59%, which was close to the expected 23 and 41.69%. This study determined a freeze-dried formulation of rh-aFGF that meets the requirements of freeze-dried formalization integrity and maintains biological activity, providing reliable support for the subsequent development of related drugs.

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Objective: To study the microanatomic structure of the subtemporal transtentorial approach to the lateral side of the brainstem, and to provide anatomical information that will assist clinicians to perform surgeries on the lateral, circumferential, and petroclival regions of the brainstem. Methods: Anatomical investigations were conducted on 8 cadaveric head specimens (16 sides) using the infratemporal transtentorial approach. The heads were tilted to one side, with the zygomatic arch at its highest point. Then, a horseshoe incision was made above the auricle. The incision extended from the midpoint of the zygomatic arch to one third of the mesolateral length of the transverse sinus, with the flap turned towards the temporal part. After removing the bone, the arachnoid and the soft meninges were carefully stripped under the microscope. The exposure range of the surgical approach was observed and the positional relationships of relevant nerves and blood vessels in the approach were clarified. Important structures were photographed and the relevant parameters were measured. Results: The upper edge of the zygomatic arch root could be used to accurately locate the base of the middle cranial fossa. The average distances of the star point to the apex of mastoid, the star point to the superior ridge of external auditory canal, the anterior angle of parietomastoid suture to the superior ridge of external auditory canal, and the anterior angle of parietomastoid suture to the star point of the 10 adult skull specimens were 47.23 mm, 45.27 mm, 26.16 mm, and 23.08 mm, respectively. The subtemporal approach could fully expose the area from as high as the posterior clinoid process to as low as the petrous ridge and the arcuate protuberance after cutting through the cerebellar tentorium. The approach makes it possible to handle lesions on the ventral or lateral sides of the middle clivus, the cistern ambiens, the midbrain, midbrain, and pons. In addition, the approach can significantly expand the exposure area of the upper part of the tentorium cerebelli through cheekbone excision and expand the exposure range of the lower part of the tentorium cerebelli through rock bone grinding technology. The total length of the trochlear nerve, distance of the trochlear nerve to the tentorial edge of cerebellum, length of its shape in the tentorial mezzanine, and its lower part of entering into the tentorium cerebelli to the petrosal ridge were (16.95±4.74) mm, (1.27±0.73) mm, (5.72±1.37) mm, and (4.51±0.39) mm, respectively. The cerebellar tentorium could be safely opened through the posterior clinoid process or arcuate protrusion for localization. The oculomotor nerve could serve as an anatomical landmark to locate the posterior cerebral artery and superior cerebellar artery. Conclusion: Through microanatomic investigation, the exposure range and intraoperative difficulties of the infratemporal transtentorial approach can be clarified, which facilitates clinicians to accurately and safely plan surgical methods and reduce surgical complications.

Phylogenomic insights into the origin and evolutionary history of evergreen broadleaved forests in East Asia under Cenozoic climate change.

The evergreen versus deciduous leaf habit is an important functional trait for adaptation of forest trees and has been hypothesized to be related to the evolutionary processes of the component species under paleoclimatic change, and potentially reflected in the dynamic history of evergreen broadleaved forests (EBLFs) in East Asia. However, knowledge about the shift of evergreen versus deciduous leaf with the impact of paleoclimatic change using genomic data remains rare. Here, we focus on the Litsea complex (Lauraceae), a key lineage with dominant species of EBLFs, to gain insights into how evergreen versus deciduous trait shifted, providing insights into the origin and historical dynamics of EBLFs in East Asia under Cenozoic climate change. We reconstructed a robust phylogeny of the Litsea complex using genome-wide single-nucleotide variants (SNVs) with eight clades resolved. Fossil-calibrated analyses, diversification rate shifts, ancestral habit, ecological niche modelling and climate niche reconstruction were employed to estimate its origin and diversification pattern. Taking into account studies on other plant lineages dominating EBLFs of East Asia, it was revealed that the prototype of EBLFs in East Asia probably emerged in the Early Eocene (55-50 million years ago [Ma]), facilitated by the greenhouse warming. As a response to the cooling and drying climate in the Middle to Late Eocene (48-38 Ma), deciduous habits were evolved in the dominant lineages of the EBLFs in East Asia. Up to the Early Miocene (23 Ma), the prevailing of East Asian monsoon increased the extreme seasonal precipitation and accelerated the emergence of evergreen habits of the dominant lineages, and ultimately shaped the vegetation resembling that of today.

Dynamic changes in microglia in the mouse hippocampus during administration and withdrawal of the CSF1R inhibitor PLX3397.

Pexidartinib (PLX3397), a colony-stimulating factor-1 receptor (CSF1R) inhibitor, is currently in phase 1-3 clinical trials as a treatment for a variety of tumours. CSF1R signalling regulates the development, survival and maintenance of microglia, the resident brain innate immune cells. In this study, we examined the effects of PLX3397 in the drinking water of mice on microglia in the hippocampus using ionized calcium-binding adapter molecule 1 (Iba1, a microglial marker) immunocytochemistry. A high concentration of PLX3397 (1 mg/mL) significantly decreased the density of Iba1-immunoreactive cells after 7 days of exposure, but a low concentration of PLX3397 (0.5 mg/mL) did not. In addition, both low and high concentrations of PLX3397 significantly increased the intersection number, total length and maximum length of microglial processes in male mice. PLX3397 administered for 21 days eliminated microglia with 78% efficiency in males and 84% efficiency in females. Significant increases in microglial processes were found after both seven and 21 days of PLX3397 exposure in males, whereas decreases in microglial processes were observed after both 14 and 21 days of exposure in females. After PLX3397 withdrawal following its administration for 14 days in males, the soma size quickly returned to normal levels within a week. However, the microglial density, intersection number and total length of microglial processes after 3 days of recovery stabilized to untreated levels. In summary, these findings provide detailed insight into the dynamic changes in microglial number and morphology in the hippocampus in a dose- and time-dependent manner after PLX3397 treatment and withdrawal.

Low polarization-sensitive ultra-broadband anti-reflection coatings with improved reliability.

Broader spectra, lower reflectivity and higher reliability are the performance requirements for broadband antireflective (BBAR) films. In this work, a BBAR film structure was proposed, which maintains extremely low reflectivity, ultra-wide spectra, low polarization sensitivity and practical reliability. The BBAR film consists of a dense multilayer interference stack on the bottom and a nano-grass-like alumina (NGLA) layer with a gradient low refractive index distribution on the top. The film was deposited by atomic layer deposition, while the NGLA layer was formed by means of a hot water bath on Al2O3 layer. The top NGLA layer has extremely high porosity and ultra-low refractive index, along with extremely fragile structure. To surmount the fragility of NGLA layer, a sub-nano layer of SiO2 was grown by atomic layer deposition to solidify its structure and also to adjust the refractive index with different thicknesses of SiO2. Finally, in the wide wavelength range of 400-1100 nm, the average transmittance of the double-sided coated fused quartz reaches 99.2%. The absorption, light scattering, reliability and polarization characteristics of BBAR films were investigated. An optimized BBAR film with low polarization-sensitivity and improved reliability was realized, which should be potentially promising for application in optical systems.

Clinical applications of the mastoid emissary vein.

PURPOSE: During retrosigmoid craniotomy, the mastoid emissary vein (MEV) can be a source of considerable bleeding during the operation, especially when the larger diameter MEV or sigmoid sinus is torn. In this study, we evaluated the relevant structure of the MEV for their anatomy and applied the data in surgery to summarize their clinical significance. METHODS: The posterior craniocervical regions of 15 silicon-injected Chinese human cadaver specimens were dissected to expose the MEV and adjacent structures. Fifty-one patients who were scheduled to undergo retrosigmoid craniotomy were selected. All patients underwent preoperative routine CT of the head. The relevant data were collected on cadaveric anatomy and CT. Eventually, all patients underwent retrosigmoid craniotomy and the MEV was observed during the operation. RESULTS: In cadaver specimens, the prevalence of the MEV was 90.0%. It originated from the middle and lower parts of the posterior wall of the sigmoid sinus and extended in the posterior direction in the mastoid process, usually having 1-2 external openings (86.7%) and only 1 internal opening. The intraosseous courses of the MEV were classified as straight and curved. The straight type accounted for 57.9%, and the curved type for 42.1%. The mean diameter of the MEV was 1.84 ± 0.85 mm, and the straight length of the MEV inside the mastoid process was 11.93 ± 3.58 mm. In 16.7% and 6.7% of all cadaver specimens, the MEV diameter was greater than 2.5 and 4 mm, respectively. In 51 patients (bilateral), routine head CT scan showed the MEV in 49.0% of the patients, and the MEV diameter was greater than 2.5 and 4 mm, respectively, in 17.6% (18/102) and 3.9% (4/102) of the cases. During surgery (unilateral) in the 51 patients, 48 had the MEV and 3 had no MEV. None of the patients had sigmoid sinus tears or massive bleeding. CONCLUSION: In the process of retrosigmoid craniotomy, detailed anatomical knowledge of the MEV, well-planned CT scan, and meticulous microsurgical techniques are key for successful operation, which can reduce the occurrence of complications.

Delta Infection After Vaccination Elicits Potent Neutralizing Immunity Against Severe Acute Respiratory Syndrome Coronavirus 2 Omicron.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant extensively escape neutralizing antibodies by vaccines or infection. We assessed serum neutralizing activity in sera from Delta infection after vaccination and Delta infection only against SARS-CoV-2 Wuhan-Hu-1 (WA1), Beta, Delta, and Omicron. Sera from Delta infection only could neutralize WA1 and Delta but almost completely lost capacity to neutralize Beta and Omicron. However, Delta infection after vaccination resulted in a significant increase of serum neutralizing activity against WA1, Beta, and Omicron. This study demonstrates that breakthrough infection of Delta substantially induced high potency humoral immune response against the Omicron variant and other emerged variants.