B cells in head and neck squamous cell carcinoma: current opinion and novel therapy.

Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumour. Despite advancements in surgery, radiotherapy and chemotherapy, which have improved the prognosis of most patients, a subset of patients with poor prognoses still exist due to loss of surgical opportunities, postoperative recurrence, and metastasis, among other reasons. The tumour microenvironment (TME) is a complex organization composed of tumour, stromal, and endothelial cells. Communication and interaction between tumours and immune cells within the TME are increasingly being recognized as pivotal in inhibiting or promoting tumour development. Previous studies on T cells in the TME of HNSCC have yielded novel therapeutic possibilities. However, the function of B cells, another adaptive immune cell type, in the TME of HNSCC patients has yet to be determined. Recent studies have revealed various distinct subtypes of B cells and tertiary lymphoid structures (TLSs) in the TME of HNSCC patients, which are believed to impact the efficacy of immune checkpoint inhibitors (ICIs). Therefore, this paper focuses on B cells in the TME to explore potential directions for future immunotherapy for HNSCC.

A novel tyrosine tRNA-derived fragment, tRFTyr, induces oncogenesis and lactate accumulation in LSCC by interacting with LDHA.

BACKGROUND: Transfer (t)RNA-derived small RNA (tsRNA), generated from precursor or mature tRNA, is a new type of small non-coding RNA (sncRNA) that has recently been shown to play a vital role in human cancers. However, its role in laryngeal squamous cell carcinoma (LSCC) remains unclear. METHODS: We elucidated the expression profiles of tsRNAs in four paired LSCC and non-neoplastic tissues by sequencing and verified the sequencing data by quantitative real-time PCR (qRT-PCR) of 60 paired samples. The tyrosine-tRNA derivative tRFTyr was identified as a novel oncogene in LSCC for further study. Loss-of-function experiments were performed to evaluate the roles of tRFTyr in tumorigenesis of LSCC. Mechanistic experiments including RNA pull-down, parallel reaction monitoring (PRM) and RNA immunoprecipitation (RIP) were employed to uncover the regulatory mechanism of tRFTyr in LSCC. RESULTS: tRFTyr was significantly upregulated in LSCC samples. Functional assays showed that knockdown of tRFTyr significantly suppressed the progression of LSCC. A series of mechanistic studies revealed that tRFTyr could enhance the phosphorylated level of lactate dehydrogenase A (LDHA) by interacting with it. The activity of LDHA was also activated, which induced lactate accumulation in LSCC cells. CONCLUSIONS: Our data delineated the landscape of tsRNAs in LSCC and identified the oncogenic role of tRFTyr in LSCC. tRFTyr could promote lactate accumulation and tumour progression in LSCC by binding to LDHA. These findings may aid in the development of new diagnostic biomarkers and provide new insights into therapeutic strategies for LSCC.

Spatial and temporal variations of vegetation cover and its influencing factors in Shandong Province based on GEE.

Economic development has rapidly progressed since the implementation of reform and opening up policies, posing significant challenges to sustainable development, especially to vegetation, which plays a crucial role in maintaining ecosystem service functions and promoting green low-carbon transformations. In this study, we estimated the fractional vegetation cover (FVC) in Shandong Province from 2000 to 2020 using the Google Earth Engine (GEE) platform. The spatial and temporal changes in FVC were analyzed using gravity center migration analysis, trend analysis, and geographic detector, and the vegetation changes of different land use types were analyzed to reveal the internal driving mechanism of FVC changes. Our results indicate that vegetation cover in Shandong Province was in good condition during the period 2000 to 2020. The high vegetation cover classes dominated, and overall changes were relatively small, with the center of gravity of vegetation cover generally shifting towards the southwest. Land use type, soil type, population density, and GDP factors had the most significant impact on vegetation cover change in Shandong Province. The interaction of these factors enhanced the effect on vegetation cover change, with land use type and soil type having the highest degree of influence. The observational results of this study can provide data support for the policy makers to formulate new ecological restoration strategies, and the findings would help facilitate the sustainability management of regional ecosystem and natural resource planning.

AGs-Unet: Building Extraction Model for High Resolution Remote Sensing Images Based on Attention Gates U Network.

Building contour extraction from high-resolution remote sensing images is a basic task for the reasonable planning of regional construction. Recently, building segmentation methods based on the U-Net network have become popular as they largely improve the segmentation accuracy by applying 'skip connection' to combine high-level and low-level feature information more effectively. Meanwhile, researchers have demonstrated that introducing an attention mechanism into U-Net can enhance local feature expression and improve the performance of building extraction in remote sensing images. In this paper, we intend to explore the effectiveness of the primeval attention gate module and propose the novel Attention Gate Module (AG) based on adjusting the position of 'Resampler' in an attention gate to Sigmoid function for a building extraction task, and a novel Attention Gates U network (AGs-Unet) is further proposed based on AG, which can automatically learn different forms of building structures in high-resolution remote sensing images and realize efficient extraction of building contour. AGs-Unet integrates attention gates with a single U-Net network, in which a series of attention gate modules are added into the 'skip connection' for suppressing the irrelevant and noisy feature responses in the input image to highlight the dominant features of the buildings in the image. AGs-Unet improves the feature selection of the attention map to enhance the ability of feature learning, as well as paying attention to the feature information of small-scale buildings. We conducted the experiments on the WHU building dataset and the INRIA Aerial Image Labeling dataset, in which the proposed AGs-Unet model is compared with several classic models (such as FCN8s, SegNet, U-Net, and DANet) and two state-of-the-art models (such as PISANet, and ARC-Net). The extraction accuracy of each model is evaluated by using three evaluation indexes, namely, overall accuracy, precision, and intersection over union. Experimental results show that the proposed AGs-Unet model can improve the quality of building extraction from high-resolution remote sensing images effectively in terms of prediction performance and result accuracy.

Effects of food matrix and probiotics on the bioavailability of curcumin in different nanoformulations.

BACKGROUND: Nanoparticles can improve the bioavailability of bioactive compounds. Concomitant intake of food can affect pharmacokinetic profiles by altering dissolution, absorption, metabolism, and elimination behavior. Studies on the effects of food and its supplements on the bioavailability of bioactives in nanoformulations are few. In this study, the effects of typical food (milk, sugar, high-fat diet, and regular kibble) and a widely consumed probiotic [Bifidobacterium lactis Bb-12® (Bb-12)] on the bioavailability of curcumin in four formulations [simply suspended curcumin (Cur-SS) and curcumin in nanoemulsions (Cur-NEs), in single-walled carbon nanotubes (Cur-SWNTs), and in nanostructured lipid carriers (Cur-NLCs)] were investigated. RESULTS: Fasting treatment and sugar co-ingestion can significantly enhance the bioavailability of curcumin in Cur-NEs and Cur-SWNTs, respectively. Compared with the fasting treatment, co-ingestion with regular kibble reduced the absorption of curcumin in Cur-NEs and Cur-SWNTs. Ingesting milk along with Cur-NE is also not recommended. The mechanisms behind these phenomena were briefly discussed. This study revealed for the first time that the intestinal colonization of Bb-12 reduces the bioavailability of curcumin and this reduction can be attenuated by nanoformulations SWNTs and NLCs, but not NEs. The reason for this difference was the protective effects of the former two nanoformulations against curcumin degradation by Bb-12 according to in vitro experiments. CONCLUSION: Dietary status (including supplementary probiotics) can dramatically influence the bioavailability of curcumin in nanoformulations. © 2021 Society of Chemical Industry.

Coupling Paternò-Büchi Reaction with Surface-Coated Probe Nanoelectrospray Ionization Mass Spectrometry for In Vivo and Microscale Profiling of Lipid C═C Location Isomers in Complex Biological Tissues.

Lipids are important structural components of biological systems, and lipid C═C locations play important roles in their biophysical and biochemical properties. Rapid, in vivo, in situ, and microscale lipidomics investigation (including precise identification of lipid C═C locations and isomers) of biological specimen has great potential for clinical diagnosis, biological studies, and biomarker discovery. Here we report a novel lipidomics methodology by coupling Paternò-Büchi (PB) reaction with surface-coated probe nanoelectrospray ionization mass spectrometry (SCP-nanoESI-MS) for in vivo, in situ, and microscale analysis of lipid species and C═C location isomers in complex biological tissues. The proposed SCP-PB-nanoESI-MS method was performed by application of a biocompatible solid-phase microextraction (SPME) probe for in vivo, in situ, and microscale sampling and extraction of lipids from biological tissues, and then some spray solvent containing PB reagent was applied to desorb lipid species enriched on SPME probe within a nanospray tip. Subsequently, ultraviolet irradiation was employed to initiate PB reaction for unsaturated lipids within the nanospray tip. After that, a high voltage was applied on the SPME probe to induce nanoESI for MS analysis under ambient and open-air conditions, and collision-induced dissociation was performed to the PB reaction product ions for determination of lipid C═C locations and isomers. By using our proposed SCP-BP-nanoESI-MS method, microscale investigation of lipid compositions and C═C location isomers for lipid droplet of Perilla seed and human intestinal tissue were successfully achieved, and in vivo analysis of lipid species and C═C locations for zebrafish was accomplished.

The interaction between Vav1 and EBNA1 promotes survival of Burkitt's lymphoma cells by down-regulating the expression of Bim.

Vav1 is a guanine nucleotide exchange factor (GEF) predominantly expressed in hematopoietic cells, and functions in the development and antigen-stimulated response of lymphocytes. Burkitt's lymphoma (BL) is characterized as transformed B cell lymphoma, and is highly associated with Epstein-Barr virus (EBV). EBV nuclear antigen 1 (EBNA1) is the only viral protein expressed across all three types of latency and essential for the persistence of EBV genome. It is not clear yet how EBNA1 contributes to the growth advantage of latently infected cells such as in EBV+ lymphoma B cells. Here, we reported that Vav1 interacts with EBNA1 via its C-terminal SH3 domain. This interaction suppresses the expression of a pro-apoptotic Bcl-2 family member, Bim, resulting in the resistance of the BL cells to apoptotic inductions. Our data uncovered Vav1 as a novel target for EBNA1, and suggested a pro-survival role of Vav1 in the pathogenesis of EBV associated BLs.

Identification of novel Kv1.3 targeting venom peptides by a single round of autocrine-based selection.

Venom peptides are an excellent source of pharmacologically active molecules for ion channels that have been considered as promising drug targets. However, mining venoms that interact with ion channel remains challenging. Previously an autocrine based high throughput selection system was developed to screen venom peptide library but the method includes repetitious selection rounds that may cause loss of valuable hits. To simplify the selection process, next generation sequencing was employed to directly identify the positive hits after a single round of selection. The advantage of the improved system was demonstrated by the discovery of 3 novel Kv1.3 targeting venom peptides among which Kappa-thalatoxin-Tas2a is a potent Kv1.3 antagonist. Therefore, this simplified method is efficient to identify novel venom peptides that target ion channels.

A microscale solid-phase microextraction probe for the in situ analysis of perfluoroalkyl substances and lipids in biological tissues using mass spectrometry.

The simultaneous analysis of perfluoroalkyl substances (PFASs) and lipids in biological tissues is of importance, especially for in situ and microscale analysis, because it provides significant information to understand the relevance of content, composition, and distribution of lipids to the bioaccumulation of PFASs as well as lipid metabolism affected by the biotoxicity of PFASs. In this study, we report the development of a novel ambient mass spectrometry method for the rapid, in situ, and microscale analysis of PFASs and lipids simultaneously in biological tissues for the investigation of their biological correlation. A microscale solid-phase microextraction (SPME) probe with a probe-end diameter of several-µm was employed for in situ and microscale sampling of biological tissues after PFAS exposure. The SPME probe showed a desirable capacity for the enrichment of PFASs and lipid species simultaneously. After sampling and extraction, the loaded SPME probe was directly applied for nanoESI-MS analysis under ambient and open-air conditions. A high-resolution Fourier transform ion cyclotron resonance (FTICR) mass spectrometer operated in the field-induced mode was introduced to record mass spectra using fast polarity switching between positive and negative ion detection. Most of the lipid species were recorded in the positive ion mass spectrum, and PFASs were recorded in the negative ion mass spectrum. By using the developed method, the in situ analysis of PFASs and lipids in the muscle, brain, heart, kidney, liver, and intestine of zebrafish was realized. In addition, simultaneously imaging PFASs and lipids in individual Daphnia magna was successfully achieved for the investigation of their biological correlation.

Biocompatible Surface-Coated Probe for in Vivo, in Situ, and Microscale Lipidomics of Small Biological Organisms and Cells Using Mass Spectrometry.

Lipidomics is a significant way to understand the structural and functional roles that lipids play in biological systems. Although many mass spectrometry (MS)-based lipidomics strategies have recently achieve remarkable results, in vivo, in situ, and microscale lipidomics for small biological organisms and cells have not yet been obtained. In this article, we report a novel lipidomics methodology for in vivo, in situ, and microscale investigation of small biological organisms and cells using biocompatible surface-coated probe nanoelectrospray ionization mass spectrometry (BSCP-nanoESI-MS). A novel biocompatible surface-coated solid-phase microextration (SPME) probe is prepared, which possesses a probe-end diameter of less than 5 µm and shows excellent enrichment capacity toward lipid species. In vivo extraction of living biological organisms (e.g., zebrafishes), in situ sampling a precise position of small organisms (e.g., Daphnia magna), and even microscale analysis of single eukaryotic cells (e.g., HepG2) are easily achieved by the SPME probe. After extraction, the loaded SPME probe is directly applied for nanoESI-MS analysis, and a high-resolution mass spectrometer is employed for recording spectra and identifying lipid species. Compared with the conventional direct infusion shotgun MS lipidomics, our proposed methodology shows a similar result of lipid profiles but with simpler sample pretreatment, less sample consumption, and shorter analytical times. Lipidomics of zebrafish, Daphnia magna, and HepG2 cell populations were investigated by our proposed BSCP-nanoESI-MS methodology, and abundant lipid compositions were detected and identified and biomarkers were obtained via multivariate statistical analysis.

Herpes Simplex Virus 1 Induces Phosphorylation and Reorganization of Lamin A/C through the γ134.5 Protein That Facilitates Nuclear Egress.

Herpes simplex virus 1 (HSV-1) remodels nuclear membranes during virus egress. Although the UL31 and UL34 proteins control nucleocapsid transit in infected cells, the molecular interactions required for their function are unclear. Here we report that the γ134.5 gene product of HSV-1 facilitates nucleocapsid release to the cytoplasm through bridging the UL31/UL34 complex, cellular p32, and protein kinase C. Unlike wild-type virus, an HSV mutant devoid of γ134.5 or its amino terminus is crippled for viral growth and release. This is attributable to a defect in virus nuclear egress. In infected cells, wild-type virus recruits protein kinase C to the nuclear membrane and triggers its activation, whereas the γ134.5 mutants fail to exert such an effect. Accordingly, the γ134.5 mutants are unable to induce phosphorylation and reorganization of lamin A/C. When expressed in host cells γ134.5 targets p32 and protein kinase C. Meanwhile, it communicates with the UL31/UL34 complex through UL31. Deletion of the amino terminus from γ134.5 disrupts its activity. These results suggest that disintegration of the nuclear lamina mediated by γ134.5 promotes HSV replication. IMPORTANCE: HSV nuclear egress is a key step that determines the outcome of viral infection. While the nuclear egress complex mediates capsid transit across the nuclear membrane, the regulatory components are not clearly defined in virus-infected cells. We report that the γ134.5 gene product, a virulence factor of HSV-1, facilitates nuclear egress cooperatively with cellular p32, protein kinase C, and the nuclear egress complex. This work highlights a viral mechanism that may contribute to the pathogenesis of HSV infection.

The Us3 Protein of Herpes Simplex Virus 1 Inhibits T Cell Signaling by Confining Linker for Activation of T Cells (LAT) Activation via TRAF6 Protein.

Herpes simplex virus 1 (HSV-1) is the most prevalent human virus and causes global morbidity because the virus is able to infect multiple cell types. Remarkably, HSV infection switches between lytic and latent cycles, where T cells play a critical role. However, the precise way of virus-host interactions is incompletely understood. Here we report that HSV-1 productively infected Jurkat T-cells and inhibited antigen-induced T cell receptor activation. We discovered that HSV-1-encoded Us3 protein interrupted TCR signaling and interleukin-2 production by inactivation of the linker for activation of T cells. This study unveils a mechanism by which HSV-1 intrudes into early events of TCR-mediated cell signaling and may provide novel insights into HSV infection, during which the virus escapes from host immune surveillance.

Parthenolide induces autophagy via the depletion of 4E-BP1.

Parthenolide (PTL) is a sesquiterpene lactone isolated from feverfew and exhibits potent antitumor activity against various cancers. Many studies indicate that PTL treatment leads to apoptosis, however, the mechanism has not been defined. Here, we observed that cells underwent autophagy shortly after PTL treatment. Inhibition of autophagy by knocking out autophagy associated gene atg5 blocked PTL-induced apoptosis. Surprisingly, PTL decreased the level of translation initiation factor eIF4E binding protein 1 (4E-BP1) in correlation with autophagy. Ectopic expression or shRNA knockdown of 4E-BP1 further verified the effect of 4E-BP1 on PTL-induced autophagy. Meanwhile, PTL elevated the cellular reactive oxygen species (ROS) which located upstream of the depletion of 4E-BP1, and contributed to the consequent autophagy. This study revealed 4E-BP1 as a trigger for PTL-induced autophagy and may lead to therapeutic strategy to enhance the efficacy of anticancer drugs.

The N-terminal 20-amino acid region of guanine nucleotide exchange factor Vav1 plays a distinguished role in T cell receptor-mediated calcium signaling.

Vav1 is a guanine nucleotide exchange factor (GEF) specifically expressed in hematopoietic cells. It consists of multiple structural domains and plays important roles in T cell activation. The other highly conserved isoforms of Vav family, Vav2 and Vav3, are ubiquitously expressed in human tissues including lymphocytes. All three Vav proteins activate Rho family small GTPases, which are involved in a variety of biological processes during T cell activation. Intensive studies have demonstrated that Vav1 is indispensable for T cell receptor (TCR)-mediated signal transduction, whereas Vav2 and Vav3 function as GEFs that overlap with Vav1 on TCR-induced cytoskeleton reorganization. T cells lacking Vav1 exhibited severe defect in TCR-mediated calcium elevation, indicating that the co-existing Vav2 and Vav3 did not compensate Vav1 in calcium signaling. What is the functional particularity of Vav1 in lymphocytes? In this study, we identified the N-terminal 20 amino acids of Vav1 in the calponin homology (CH) domain to be essential for its interaction with calmodulin (CaM) that leads to TCR-induced calcium mobilization. Substitution of the 1-20 amino acids of Vav1 with those of Vav2 or Vav3 abolished the association with CaM, and the N-terminal mutations of Vav1 failed to potentiate normal TCR-induced calcium mobilization, that in turn, suspended nuclear factor of activated T cells (NFAT) activation and IL-2 production. This study highlights the importance of the N-terminal 20 aa of Vav1 for CaM binding, and provides new insights into the distinguished and irreplaceable role of Vav1 in T cell activation and signal transduction.

Effects of Temperature, Ionic Strength and Humic Acid on the Transport of Graphene Oxide Nanoparticles in Geosynthetic Clay Liner.

With the wide application of graphene oxide nanoparticles (GONPs), a great amount of GONP waste is discarded and concentrated in landfills. It has been proven that GONPs have strong toxicity and could gather toxic substances due to their high adsorption capacity. GONPs will seriously pollute the surrounding environment if they leak through the geosynthetic clay liner (GCL) in landfills. To investigate various factors (temperature, ionic strength (IS) and humic acid (HA)) on the transport and retention of GONPs in the GCL, a self-designed apparatus was created and column tests were carried out. The experimental results show that GONPs could be transported through the GCL. The mobility and sorption ratio of GONPs in GCL decreased with an increase in temperature and IS, and increased with an increase in HA. The temperature had little effect on the deposition ratio of GONPs in the GCL. The deposition ratio of GONPs in the GCL increased with IS, and decreased with an increase in HA. The transport of GONPs in GCL, glass beads and quartz sand was compared, and the results show that the retention ability of the GCL is much better than other porous materials. The experimental results could provide significant references for the pollution treatment in landfills.

Influence of Electrospinning Parameters on the Morphology of Electrospun Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Fibrous Membranes and Their Application as Potential Air Filtration Materials.

A large number of non-degradable materials have severely damaged the ecological environment. Now, people are increasingly pursuing the use of environmentally friendly materials to replace traditional chemical materials. Polyhydroxyalkonates (PHAs) are receiving increasing attention because of the unique biodegradability and biocompatibility they offer. However, the applications of PHAs are still limited due to high production costs and insufficient study. This project examines the optimal electrospinning parameters for the production of PHA-based fibrous membranes for air filtration. A common biodegradable polyester, Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), was electrospun into a nanofibrous membrane with a well-controlled surface microstructure. In order to produce smooth, bead-free fibers with micron-scale diameters, the effect of the process parameters (applied electric field, solution flow rate, inner diameter of hollow needle, and polymer concentration) on the electrospun fiber microstructure was optimized. The well-defined fibrous structure was optimized at an applied electric field of 20 kV, flow rate of 0.5 mL/h, solution concentration of 12 wt.%, and needle inner diameter of 0.21 mm. The morphology of the electrospun PHBV fibrous membrane was observed by scanning electron microscopy (SEM). Fourier transform infrared (FTIR) and Raman spectroscopy were used to explore the chemical signatures and phases of the electrospun PHBV nanofiber. The ball burst strength (BBS) was measured to assess the mechanical strength of the membrane. The small pore size of the nanofiber membranes ensured they had good application prospects in the field of air filtration. The particle filtration efficiency (PFE) of the optimized electrospun PHBV fibrous membrane was above 98% at standard atmospheric pressure.

Non-targeted effects of nitrification inhibitors on soil free-living nitrogen fixation modified with weed management.

Biological nitrogen fixation and nitrification inhibitor applications contribute to improving soil nitrogen (N) availability, however, free-living N fixation affected by nitrification inhibitors has not been effectively evaluated in soils under different weed management methods. In this study, the effects of the nitrification inhibitors dicyandiamide (DCD) and 3, 4-dimethylpyrazole phosphate (DMPP) on the nitrogenase, nifH gene，and diazotrophic communities in soils under different weed management methods (AMB, weeds growth without mowing or glyphosate spraying; GS, glyphosate spraying; MSG, mowing and removing weeds and glyphosate spraying; and WM, mowing aboveground weeds) were investigated. Compared to the control counterparts, the DCD application decreased soil nitrogenase activity and nifH gene abundance by 4.5 % and 37.9 %, respectively, under the GS management method, and the DMPP application reduced soil nitrogenase activity by 20.4 % and reduced the nifH gene abundance by 83.4 % under the MSG management method. The application of nitrification inhibitors significantly elevated soil NH4+-N contents but decreased NO3--N contents, which had adverse impacts on soil nifH gene abundance and nitrogenase activity. The nifH gene abundances were also negatively impacted by dissolved organic N and Geobacter but were positively affected by available phosphorus and diazotrophic community structures. Nitrification inhibitors significantly inhibited Methylocella but stimulated Rhizobiales and affected soil diazotrophic communities. The nitrification inhibitors DCD and DMPP significantly altered soil diazotrophic community structures, but weed management outweighed nitrification inhibitors in reshaping soil diazotrophic community structures. The non-targeted effects of the nitrification inhibitors DMPP and DCD on soil free-living N fixation were substantially influenced by the weed management methods.

Semivortex solitons and their excited states in spin-orbit-coupled binary bosonic condensates.

It is known that two-dimensional two-component fundamental solitons of the semivortex (SV) type, with vorticities (s_{+},s_{-})=(0,1) in their components, are stable ground states (GSs) in the spin-orbit-coupled (SOC) binary Bose-Einstein condensate with the contact self-attraction acting in both components, in spite of the possibility of the critical collapse in the system. However, excited states (ESs) of the SV solitons, with the vorticity set (s_{+},s_{-})=(S_{+},S_{+}+1) and S_{+}=1,2,3,..., are unstable in the same system. We construct ESs of SV solitons in the SOC system with opposite signs of the self-interaction in the two components. The main finding is stability of the ES-SV solitons, with the extra vorticity (at least) up to S_{+}=6. The threshold value of the norm for the onset of the critical collapse, N_{thr}, in these excited states is higher than the commonly known critical value, N_{c}≈5.85, associated with the single-component Townes solitons, N_{thr} increasing with the growth of S_{+}. A velocity interval for stable motion of the GS-SV solitons is found too. The results suggest a solution for the challenging problem of the creation of stable vortex solitons with high topological charges.

High serum magnesium level is associated with increased mortality in patients with sepsis: an international, multicenter retrospective study.

Magnesium imbalances commonly exist in septic patients. However, the association of serum magnesium levels with mortality in septic patients remains uncertain. Herein, we elucidated the association between serum magnesium and all-cause mortality in septic patients from American and Chinese cohorts by analyzing data from 9099 patients in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and 1727 patients from a university-affiliated hospital' intensive care unit in China. Patients in both cohorts were categorized into five groups based on serum magnesium quintiles from the MIMIC-IV dataset. Patients with higher serum magnesium levels exhibited an increased risk of 28-day mortality in both cohorts. The restricted cubic spline (RCS) curves revealed a progressively elevated risk of 28-day mortality with increasing serum magnesium in MIMIC-IV cohort, while a J-shaped correlation was observed in institutional cohort. Our findings have validated the association between high serum magnesium and high mortality in sepsis across different races and medical conditions. Serum magnesium levels might be useful in identifying septic patients at higher mortality risk.

Astrocyte-mediated regulation of BLAWFS1 neurons alleviates risk-assessment deficits in DISC1-N mice.

Assessing and responding to threats is vital in everyday life. Unfortunately, many mental illnesses involve impaired risk assessment, affecting patients, families, and society. The brain processes behind these behaviors are not well understood. We developed a transgenic mouse model (disrupted-in-schizophrenia 1 [DISC1]-N) with a disrupted avoidance response in risky settings. Our study utilized single-nucleus RNA sequencing and path-clamp coupling with real-time RT-PCR to uncover a previously undescribed group of glutamatergic neurons in the basolateral amygdala (BLA) marked by Wolfram syndrome 1 (WFS1) expression, whose activity is modulated by adjacent astrocytes. These neurons in DISC1-N mice exhibited diminished firing ability and impaired communication with the astrocytes. Remarkably, optogenetic activation of these astrocytes reinstated neuronal excitability via D-serine acting on BLAWFS1 neurons' NMDA receptors, leading to improved risk-assessment behavior in the DISC1-N mice. Our findings point to BLA astrocytes as a promising target for treating risk-assessment dysfunctions in mental disorders.