Brain abnormalities in survivors of COVID-19 after 2-year recovery: a functional MRI study.

Background: A variety of symptoms, particularly cognitive, psychiatric and neurological symptoms, may persist for a long time among individuals recovering from COVID-19. However, the underlying mechanism of these brain abnormalities remains unclear. This study aimed to investigate the long-term neuroimaging effects of COVID-19 infection on brain functional activities using resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Fifty-two survivors 27 months after infection (mild-moderate group: 25 participants, severe-critical: 27 participants), from our previous community participants, along with 35 healthy controls, were recruited to undergo fMRI scans and comprehensive cognitive function measurements. Participants were evaluated by subjective assessment of Cognitive Failures Questionnaire-14 (CFQ-14) and Fatigue Scale-14 (FS-14), and objective assessment of Montreal Cognitive Assessment (MoCA), N-back, and Simple Reaction Time (SRT). Each had rs-fMRI at 3T. Measures such as the amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo) were calculated. Findings: Compared with healthy controls, survivors of mild-moderate acute symptoms group and severe-critical group had a significantly higher score of cognitive complains involving cognitive failure and mental fatigue. However, there was no difference of cognitive complaints between two groups of COVID-19 survivors. The performance of three groups was similar on the score of MoCA, N-back and SRT. The rs-fMRI results showed that COVID-19 survivors exhibited significantly increased ALFF values in the left putamen (PUT.L), right inferior temporal gyrus (ITG.R) and right pallidum (PAL.R), while decreased ALFF values were observed in the right superior parietal gyrus (SPG.R) and left superior temporal gyrus (STG.L). Additionally, decreased ReHo values in the right precentral gyrus (PreCG.R), left postcentral gyrus (PoCG.L), left calcarine fissure and surrounding cortex (CAL.L) and left superior temporal gyrus (STG.L). Furthermore, significant negative correlations between the ReHo values in the STG.L, and CFQ-14 and mental fatigue were found. Interpretation: This long-term study suggests that individuals recovering from COVID-19 continue to experience cognitive complaints, psychiatric and neurological symptoms, and brain functional alteration. The rs-fMRI results indicated that the changes in brain function in regions such as the putamen, temporal lobe, and superior parietal gyrus may contribute to cognitive complaints in individuals with long COVID even after 2-year infection. Funding: The National Programs for Brain Science and Brain-like Intelligence Technology of China, the National Natural Science Foundation of China, Natural Science Foundation of Beijing Municipality of China, and the National Key Research and Development Program of China.

Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer.

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

Two Different Three-Dimensional Uranium-Containing Polymolybdates Based on Zn(II) for the Heterogeneous Catalytic Construction of C-N Bond.

The introduction of transition metal (TM) ions into polyoxometalates (POMs) cannot only bring about interesting structural diversities but also enable changes in properties. However, TM-containing Silverton-type polyoxomolybdates are still lacking in terms of structural diversity and application development. Herein, two Zn(II)-containing Silverton-type {UMo12O42}-based polyoxomolybdates, H1.89Na4.11(H2O)9Zn[UMo12O42]·4.5H2O (Zn-1) and H1.8Na4.2(H2O)12Zn[UMo12O42] (Zn-2) were hydrothermally synthesized, demonstrating a practical strategy to assembly of TM-containing Silverton-type POMs. Zn-1 is proven to be an excellent and recyclable heterogeneous catalyst in cross-dehydrogenation coupling of 1,4-naphthoquinones with amines reactions, and a series of 2-amino-1,4-naphthoquinones with potential medicinal value have been constructed.

Global Burden and Trends of Primary Liver Cancer Attributable to Comorbid Type 2 Diabetes Mellitus Among People Living with Hepatitis B: An Observational Trend Study from 1990 to 2019.

BACKGROUND: Type 2 diabetes mellitus (T2DM) increases the risk of liver cancer among people living with hepatitis B virus (HBV). Our study aimed to estimate the global burden and trends of liver cancer attributable to comorbid T2DM among people living with HBV from 1990 to 2019. METHODS: We calculated the population attributable fractions (PAFs) of liver cancer attributable to comorbid T2DM among the burden of HBV-related liver cancer. We applied the PAFs to the burden of HBV-related liver cancer derived from the Global Burden of Disease (GBD) 2019 database to obtain the burden of liver cancer attributable to HBV-T2DM comorbidity. The prevalence, disability-adjusted life year (DALY), and deaths of liver cancer attributable to the comorbidity were assessed at the global, regional, and country levels and then stratified by the sociodemographic index (SDI), sex, and age group. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends. RESULTS: In 2019, the global age-standardized prevalence and DALY rates of liver cancer attributable to HBV-T2DM comorbidity were 9.9 (8.4-11.5) and 182.4 (154.9-212.7) per 10,000,000 individuals, respectively. High-income Asia Pacific and East Asia had the highest age-standardized prevalence and DALY rates of liver cancer attributable to HBV-T2DM comorbidity, respectively. From 1990 to 2019, age-standardized prevalence and DALY rates increased in 16 out of 21 GBD regions. High-income North America had the largest annual increases in both age-standardized prevalence rates (EAPC = 6.07; 95% UI, 5.59 to 6.56) and DALY rates (EAPC = 4.77; 95% UI, 4.35 to 5.20), followed by Australasia and Central Asia. Across all SDI regions, the high SDI region exhibited the most rapid increase in age-standardized prevalence and DALY rates from 1990 to 2019. Additionally, men had consistently higher disease burdens than women across all age groups. The patterns of mortality burden and trends are similar to those of DALYs. CONCLUSIONS: The burden of liver cancer attributable to comorbid T2DM among people living with HBV has exhibited an increasing trend across most regions over the last three decades. Tailored prevention strategies targeting T2DM should be implemented among individuals living with HBV.

Regulation of hepatocyte phospholipid peroxidation signaling by a Chinese patent medicine against psychological stress-induced liver injury.

BACKGROUND: Psychological stress is associated with various diseases including liver dysfunction, yet effective intervention strategies remain lacking due to the unrevealed pathogenesis mechanism. PURPOSE: This study aims to explore the relevance between BMAL1-controlled circadian rhythms and lipoxygenase 15 (ALOX15)-mediated phospholipids peroxidation in psychological stress-induced liver injury, and to investigate whether hepatocyte phospholipid peroxidation signaling is involved in the hepatoprotective effects of a Chinese patent medicine, Pien Tze Huang (PZH). METHODS: Restraint stress models were established to investigate the underlying molecular mechanisms of psychological stress-induced liver injury and the hepatoprotective effects of PZH. Redox lipidomics based on liquid chromatography-tandem mass spectrometry was applied for lipid profiling. RESULTS: The present study discovered that acute restraint stress could induce liver injury. Notably, lipidomic analysis confirmed that phospholipid peroxidation was accumulated in the livers of stressed mice. Additionally, the essential core circadian clock gene Brain and Muscle Arnt-like Protein-1 (Bmal1) was altered in stressed mice. Circadian disruption in mice, as well as BMAL1-overexpression in human HepaRG cells, also appeared to have a significant increase in phospholipid peroxidation, suggesting that stress-induced liver injury is closely related to circadian rhythm and phospholipid peroxidation. Subsequently, arachidonate 15-lipoxygenase (ALOX15), a critical enzyme that contributed to phospholipid peroxidation, was screened as a potential regulatory target of BMAL1. Mechanistically, BMAL1 promoted ALOX15 expression via direct binding to an E-box-like motif in the promoter. Finally, this study revealed that PZH treatment significantly relieved pathological symptoms of psychological stress-induced liver injury with a potential mechanism of alleviating ALOX15-mediated phospholipid peroxidation. CONCLUSION: Our findings illustrate the critical role of BMAL1-triggered phospholipid peroxidation in psychological stress-induced liver injury and provide new insight into treating psychological stress-associated liver diseases by TCM intervention.

The Potential Reversible Transition between Stem Cells and Transient-Amplifying Cells: The Limbal Epithelial Stem Cell Perspective.

Stem cells (SCs) undergo asymmetric division, producing transit-amplifying cells (TACs) with increased proliferative potential that move into tissues and ultimately differentiate into a specialized cell type. Thus, TACs represent an intermediary state between stem cells and differentiated cells. In the cornea, a population of stem cells resides in the limbal region, named the limbal epithelial stem cells (LESCs). As LESCs proliferate, they generate TACs that move centripetally into the cornea and differentiate into corneal epithelial cells. Upon limbal injury, research suggests a population of progenitor-like cells that exists within the cornea can move centrifugally into the limbus, where they dedifferentiate into LESCs. Herein, we summarize recent advances made in understanding the mechanism that governs the differentiation of LESCs into TACs, and thereafter, into corneal epithelial cells. We also outline the evidence in support of the existence of progenitor-like cells in the cornea and whether TACs could represent a population of cells with progenitor-like capabilities within the cornea. Furthermore, to gain further insights into the dynamics of TACs in the cornea, we outline the most recent findings in other organ systems that support the hypothesis that TACs can dedifferentiate into SCs.

Bright and durable scintillation from colloidal quantum shells.

Efficient, fast, and robust scintillators for ionizing radiation detection are crucial in various fields, including medical diagnostics, defense, and particle physics. However, traditional scintillator technologies face challenges in simultaneously achieving optimal performance and high-speed operation. Herein we introduce colloidal quantum shell heterostructures as X-ray and electron scintillators, combining efficiency, speed, and durability. Quantum shells exhibit light yields up to 70,000 photons MeV-1 at room temperature, enabled by their high multiexciton radiative efficiency thanks to long Auger-Meitner lifetimes (>10 ns). Radioluminescence is fast, with lifetimes of 2.5 ns and sub-100 ps rise times. Additionally, quantum shells do not exhibit afterglow and maintain stable scintillation even under high X-ray doses (>109 Gy). Furthermore, we showcase quantum shells for X-ray imaging achieving a spatial resolution as high as 28 line pairs per millimeter. Overall, efficient, fast, and durable scintillation make quantum shells appealing in applications ranging from ultrafast radiation detection to high-resolution imaging.

Diagnostic yield using electromagnetic navigation bronchoscopy for peripheral pulmonary nodules <2 cm.

BACKGROUND: Although electromagnetic navigation bronchoscopy (ENB) is highly sensitive in the diagnosis of peripheral pulmonary nodules (PPNs), its diagnostic yield for subgroups of smaller PPNs is under evaluation. OBJECTIVES: Diagnostic yield evaluation of biopsy using ENB for PPNs <2 cm. DESIGN: The diagnostic yield, sensitivity, specificity, positive predictive value, and negative predictive value of the ENB-mediated biopsy for PPNs were evaluated. METHODS: Patients who had PPNs with diameters <2 cm and underwent ENB-mediated biopsy between May 2015 and February 2020 were consecutively enrolled. The final diagnosis was made via pathological examination after surgery. RESULTS: A total of 82 lesions from 65 patients were analyzed. The median tumor size was 11 mm. All lesions were subjected to ENB-mediated biopsy, of which 29 and 53 were classified as malignant and benign, respectively. Subsequent segmentectomy, lobectomy, or wedge resection, following pathological examinations were performed on 64 nodules from 57 patients. The overall sensitivity, specificity, positive predictive value, and negative predictive value for nodules <2 cm were 53.3%, 91.7%, 92.3%, and 51.2%, respectively. The receiver operating curve showed an area under the curve of 0.721 (p < 0.001). Additionally, the sensitivity, specificity, positive predictive value, and negative predictive value were 62.5%, 100%, 100%, and 42.9%, respectively, for nodules with diameters equal to or larger than 1 cm; and 30.8%, 86.7%, 66.7%, and 59.1%, respectively, for nodules less than 1 cm. In the subgroup analysis, neither the lobar location nor the distance of the PPNs to the pleura affected the accuracy of the ENB diagnosis. However, the spiculated sign had a negative impact on the accuracy of the ENB biopsy (p = 0.010). CONCLUSION: ENB has good specificity and positive predictive value for diagnosing PPNs <2 cm; however, the spiculated sign may negatively affect ENB diagnostic accuracy. In addition, the diagnostic reliability may only be limited to PPNs equal to or larger than 1 cm.

Antibacterial activity of pimaradienoic acid from Eleutherococcus trifoliatus (L.) S. Y. Hu.

Purpose: To investigate the antibacterial activity of pimaradienoic acid, a natural product isolated from Eleutherococcus trifoliatus. Methods: Pimaradienoic acid was purified from E. trifoliatus and tested against three Gram-positive bacteria. Minimum inhibitory concentrations (MICs) were determined, and bacterial growth curves were measured. Scanning electron microscopy (SEM) was used to observe morphological changes in bacteria after drug treatment. Results: Pimaradienoic acid exhibited concentration-dependent inhibition of the growth of the three bacteria tested. The MIC and bacterial growth dynamics results indicated that pimaradienoic acid had potent antibacterial activity. SEM revealed that pimaradienoic acid disrupted the bacterial membrane, leading to cell death. Conclusions: Pimaradienoic acid has significant antibacterial activity against Gram-positive bacteria, suggesting its potential as a novel antimicrobial agent.

Superconducting diode effect and interference patterns in kagome CsV3Sb5.

The interplay among frustrated lattice geometry, non-trivial band topology and correlation yields rich quantum states of matter in kagome systems1,2. A series of recent members in this family, AV3Sb5 (A = K, Rb or Cs), exhibit a cascade of symmetry-breaking transitions3, involving the 3Q chiral charge ordering4-8, electronic nematicity9,10, roton pair density wave11 and superconductivity12. The nature of the superconducting order is yet to be resolved. Here we report an indication of dynamic superconducting domains with boundary supercurrents in intrinsic CsV3Sb5 flakes. The magnetic field-free superconducting diode effect is observed with polarity modulated by thermal histories, suggesting that there are dynamic superconducting order domains in a spontaneous time-reversal symmetry-breaking background. Strikingly, the critical current exhibits double-slit superconductivity interference patterns when subjected to an external magnetic field. The characteristics of the patterns are modulated by thermal cycling. These phenomena are proposed as a consequence of periodically modulated supercurrents flowing along certain domain boundaries constrained by fluxoid quantization. Our results imply a time-reversal symmetry-breaking superconducting order, opening a potential for exploring exotic physics, for example, Majorana zero modes, in this intriguing topological kagome system.

Identification and biological characteristics of Enterococcus casseliflavus TN-47 isolated from Monochamus alternatus.

With the widespread use of antibiotics, the incidence of antibiotic resistance in microorganisms has increased. Monochamus alternatus is a trunk borer of pine trees. This study aimed to investigate the in vitro antimicrobial and biological characteristics of Enterococcus casseliflavus TN-47 (PP411196), isolated from the gastrointestinal tract of M. alternatus in Jilin Province, PR China. Among 13 isolates obtained from the insects, five were preliminarily screened for antimicrobial activity. E. casseliflavus TN-47, which exhibited the strongest antimicrobial activity, was identified. E. casseliflavus TN-47 possessed antimicrobial activity against Staphylococcus aureus USA300 and Salmonella enterica serovar Pullorum ATCC 19945. Furthermore, E. casseliflavus TN-47 was sensitive to tetracyclines, penicillins (ampicillin, carbenicillin, and piperacillin), quinolones and nitrofuran antibiotics, and resistant to certain beta-lactam antibiotics (oxacillin, cefradine and cephalexin), macrolide antibiotics, sulfonamides and aminoglycosides. E. casseliflavus TN-47 could tolerate low pH and pepsin-rich conditions in the stomach and grow in the presence of bile acids. E. casseliflavus TN-47 retained its strong auto-aggregating ability and hydrophobicity. This strain did not exhibit any haemolytic activity. These results indicate that E. casseliflavus TN-47 has potential as a probiotic. This study provides a theoretical foundation for the future applications of E. casseliflavus TN-47 and its secondary metabolites in animal nutrition and feed.

Application of neutrophil-to-lymphocyte-to-monocyte ratio in predicting mortality risk in adult patients with septic shock: A retrospective cohort study conducted at a single center.

Background: Sepsis is a life-threatening condition characterized by an aberrant host response to infection, resulting in multi-organ dysfunction. The application of currently available prognostic indicators for sepsis in primary hospitals is challenging. In this retrospective study, we established a novel index, the neutrophil-to-lymphocyte-to-monocyte ratio (NLMR), based on routine blood examination upon admission, and assessed its prognostic value for early mortality risk in adult patients with septic shock. Methods: This study included clinical data from adult patients with septic shock who were admitted to the hospital between January 1, 2018, and December 31, 2022. Training and validation sets were constructed, and patients were categorized into "survival" and "death" groups based on their survival status within the 28-day hospitalization period. Baseline data, including demographic characteristics and comorbidities, and laboratory results, such as complete blood count parameters, were collected for analysis. The Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were documented.The NLMR was determined through the utilization of multivariate binary logistic regression analysis, leading to the development of a risk model aimed at predicting early mortality in adult patients suffering from septic shock. Results: Overall, 112 adult patients with septic shock were enrolled in this study, with 84 and 28 patients in the training and validation sets, respectively. Multivariate binary logistic analysis revealed that the neutrophil, lymphocyte, and monocyte counts independently contributed to the mortality risk (odds ratios = 1.22, 0.08, and 0.16, respectively). The NLMR demonstrated an area under the receiver operating characteristic curve (ROC-AUC) of 0.83 for internal validation in the training set and 0.97 for external validation in the validation set. Both overall model quality values were significantly high at 0.74 and 0.91, respectively (P < 0.05). NLMR exhibited a higher ROC-AUC value of 0.88 than quick SOFA (ROC-AUC = 0.71), SOFA (ROC-AUC = 0.83), and APACHE II (ROC-AUC = 0.78). Conclusion: NLMR may be a potential marker for predicting the risk of early death in adult patients with septic shock, warranting further exploration and verification.

Assessment of causal association between the socio-economic status and osteoporosis and fractures: a bidirectional Mendelian randomization study in European population.

BACKGROUND: The relationship between socio-economic status and bone-related diseases is attracting increasing attention. Therefore, a bidirectional Mendelian randomization (MR) analysis was performed in this study. METHODS: Genetic data on factors associated with socio-economic status (average total household income before tax, years of schooling completed and Townsend Deprivation Index at recruitment), femoral neck bone mineral density (FN-BMD), heel bone mineral density (eBMD), osteoporosis, and five different sites of fracture (spine, femur, lower leg-ankle, foot, and wrist-hand fractures) were derived from genome-wide association summary statistics of European ancestry. The inverse variance weighted method was employed to obtain the causal estimates, complemented by alternative MR techniques, including MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO). Furthermore, sensitivity analyses, and multivariable MR was performed to enhance the robustness of our findings. RESULTS: A higher educational attainment was associated with an increased level of eBMD (beta:0.06, 95% CI:0.01-0.10, P = 7.24 × 10-3), and decreased risk of osteoporosis (OR:0.78, 95% CI:0.65-0.94, P = 8.49 × 10-3), spine fracture (OR:0.76, 95% CI:0.66-0.88, P = 2.94 × 10-4), femur fracture (OR:0.78, 95% CI:0.67-0.91, P = 1.33 × 10-3), lower leg-ankle fracture (OR:0.79, 95% CI:0.70-0.88, P = 2.05 × 10-5), foot fracture (OR:0.78, 95% CI:0.66-0.93, P = 5.92 × 10-3) and wrist-hand fracture (OR:0.83, 95% CI:0.73-0.95, P = 7.15 × 10-3). Further, material deprivation seemed to harm the spine fracture (OR:2.63, 95% CI:1.43-4.85, P = 1.91 × 10-3). A higher level of FN-BMD positively affected increased household income (beta:0.03, 95% CI:0.01-0.04, P = 6.78 × 10-3). All these estimates were adjusted for body mass index (BMI), type 2 diabetes, smoking initiation, and frequency of alcohol intake. CONCLUSIONS: The Mendelian randomization analyses show that higher educational levels is associated with higher eBMD, reduced risk of osteoporosis and fractures, while material deprivation is positively related to spine fracture. Enhanced FN-BMD correlates with increased household income. These findings offer valuable insights into the formulation of health guidelines and policy development.

We conducted stratified analyses to explore the causal links between socio-economic status and osteoporosis and various fractures and observed that education significantly reduced risk of osteoporosis and lower eBMD. It also lowered the risks of fractures of spine, femur, lower leg-ankle, foot, and wrist-hand, while material deprivation exhibited positive associations with spine fracture risk. Bidirectional MR analysis showed that an elevated score of FN-BMD was associated with a higher income level. Our study shows the importance of conducting routine BMD estimations and osteoporosis screening, to enhance knowledge and awareness among individuals to promote bone health and prevent fractures.

Dysregulated Ca2+ signaling, fluid secretion, and mitochondrial function in a mouse model of early Sjögren's syndrome.

Saliva is essential for oral health. The molecular mechanisms leading to physiological fluid secretion are established, but factors that underlie secretory hypofunction, specifically related to the autoimmune disease Sjögren's syndrome (SS) are not fully understood. SS-like disease was induced by the treatment with 5,6-Dimethyl-9-oxo-9H-xanthene-4-acetic acid (DMXAA), an activator of the stimulator of the interferon gene (STING) pathway. This mouse model mimics exposure to foreign cytoplasmic ribonucleotides occurring following viral and bacterial infection and thought to be an initiating event in SS. Neurotransmitter-stimulated increases in cytoplasmic [Ca2+] are central to stimulating fluid secretion, primarily by increasing the activity of the Ca2+-activated Cl- channel, TMEM16a. Paradoxically, in DMXAA-treated mice in vivo imaging demonstrated that neural-stimulation resulted in greatly enhanced Ca2+ levels when a significant reduction in fluid secretion was observed. Notably, in the disease model, the spatiotemporal characteristics of the Ca2+ signals were altered to result in global rather than largely apically confined Ca2+ rises observed physiologically. Notwithstanding the augmented Ca2+ signals, muscarinic stimulation resulted in reduced activation of TMEM16a, although there were no changes in channel abundance or absolute sensitivity to Ca2+. However, super-resolution microscopy revealed a disruption in the localization of Inositol 1,4,5-trisphosphate receptor Ca2+ release channels in relation to TMEM16a. Appropriate Ca2+ signaling is also pivotal for mitochondrial morphology and bioenergetics and secretion is an energetically expensive process. Disrupted mitochondrial morphology, a depolarized mitochondrial membrane potential, and reduced oxygen consumption rate were observed in DMXAA-treated animals compared to control animals. We report that early in SS disease, dysregulated Ca2+ signals lead to decreased fluid secretion and disrupted mitochondrial function contributing to salivary gland hypofunction and likely the progression of SS disease.

Room­Temperature Antisymmetric Magnetoresistance in van der Waals Ferromagnet Fe3GaTe2 Nanosheets.

Van der Waals (vdW) ferromagnetic materials have emerged as a promising platform for the development of 2D spintronic devices. However, studies to date are restricted to vdW ferromagnetic materials with low Curie temperature (Tc) and small magnetic anisotropy. Here, a chemical vapor transport method is developed to synthesize a high-quality room-temperature ferromagnet, Fe3GaTe2 (c-Fe3GaTe2), which boasts a high Tc = 356 K and large perpendicular magnetic anisotropy. Due to the planar symmetry breaking, an unconventional room-temperature antisymmetric magnetoresistance (MR) is first observed in c-Fe3GaTe2 devices with step features, manifesting as three distinctive states of high, intermediate, and low resistance with the sweeping magnetic field. Moreover, the modulation of the antisymmetric MR is demonstrated by controlling the height of the surface steps. This work provides new routes to achieve magnetic random storage and logic devices by utilizing the room-temperature thickness-controlled antisymmetric MR and further design room-temperature 2D spintronic devices based on the vdW ferromagnet c-Fe3GaTe2.

Predictive value of positive lymph node ratio in patients with locally advanced gastric remnant cancer.

BACKGROUND: Traditional lymph node stage (N stage) has limitations in advanced gastric remnant cancer (GRC) patients; therefore, establishing a new predictive stage is necessary. AIM: To explore the predictive value of positive lymph node ratio (LNR) according to clinicopathological characteristics and prognosis of locally advanced GRC. METHODS: Seventy-four patients who underwent radical gastrectomy and lymphadenectomy for locally advanced GRC were retrospectively reviewed. The relationship between LNR and clinicopathological characteristics was analyzed. The survival analysis was performed using Kaplan-Meier survival curves and Cox regression model. RESULTS: Number of metastatic LNs, tumor diameter, depth of tumor invasion, Borrmann type, serum tumor biomarkers, and tumor-node-metastasis (TNM) stage were correlated with LNR stage and N stage. Univariate analysis revealed that the factors affecting survival included tumor diameter, anemia, serum tumor biomarkers, vascular or neural invasion, combined resection, LNR stage, N stage, and TNM stage (all P < 0.05). The median survival time for those with LNR0, LNR1, LNR2 and LNR3 stage were 61, 31, 23 and 17 mo, respectively, and the differences were significant (P = 0.000). Anemia, tumor biomarkers and LNR stage were independent prognostic factors for survival in multivariable analysis (all P < 0.05). CONCLUSION: The new LNR stage is uniquely based on number of metastatic LNs, with significant prognostic value for locally advanced GRC, and could better differentiate overall survival, compared with N stage.

Metabolomic Analysis in Saliva and Different Brain Regions of Older Mice with Postoperative Delirium Behaviors.

Objective: Postoperative delirium (POD) has become a critical challenge with severe consequences and increased incidences as the global population ages. However, the underlying mechanism is yet unknown. Our study aimed to explore the changes in metabolites in three specific brain regions and saliva of older mice with postoperative delirium behavior and to identify potential non-invasive biomarkers. Methods: Eighteen-month-old male C57/BL6 mice were randomly assigned to the anesthesia/surgery or control group. Behavioral tests were conducted 24 h before surgery and 6, 9, and 24 h after surgery. Complement C3 (C3) and S100 calcium-binding protein B protein (S100beta) levels were measured in the hippocampus, and a metabolomics analysis was performed on saliva, hippocampus, cortex, and amygdala samples. Results: In total, 43, 33, 38, and 14 differential metabolites were detected in the saliva, hippocampus, cortex, and amygdala, respectively. "Pyruvate" "alpha-linolenic acid" and "2-oleoyl-1-palmitoy-sn-glycero-3-phosphocholine" are enriched in one common pathway and may be potential non-invasive biomarkers for POD. Common changes were observed in the three brain regions, with the upregulation of 1-methylhistidine and downregulation of D-glutamine. Conclusion: Dysfunctions in energy metabolism, oxidative stress, and neurotransmitter dysregulation are implicated in the development of POD. The identification of changes in the level of salivary metabolite biomarkers could aid in the development of noninvasive diagnostic methods for POD.

Development and validation of a clinical prediction model for early ventilator weaning in post-cardiac surgery.

Background: Weaning patients from mechanical ventilation is a critical clinical challenge post cardiac surgery. The effective liberation of patients from the ventilator significantly improves their recovery and survival rates. This study aimed to develop and validate a clinical prediction model to evaluate the likelihood of successful extubation in post-cardiac surgery patients. Method: A predictive nomogram was constructed for extubation success in individual patients, and receiver operating characteristic (ROC) and calibration curves were generated to assess its predictive capability. The superior performance of the model was confirmed using Delong's test in the ROC analysis. A decision curve analysis (DCA) was conducted to evaluate the clinical utility of the nomogram. Results: Among 270 adults included in our study, 107 (28.84%) experienced delayed extubation. A predictive nomogram system was derived based on five identified risk factors, including the proportion of male patients, EuroSCORE II, operation time, pump time, bleeding during operation, and brain natriuretic peptide (BNP) level. Based on the predictive system, five independent predictors were used to construct a full nomogram. The area under the curve values of the nomogram were 0.880 and 0.753 for the training and validation cohorts, respectively. The DCA and clinical impact curves showed good clinical utility of this model. Conclusion: Delayed extubation and weaning failure, common and potentially hazardous complications following cardiac surgery, vary in timing based on factors such as sex, EuroSCORE II, pump duration, bleeding, and postoperative BNP reduction. The nomogram developed and validated in this study can accurately predict when extubation should occur in these patients. This tool is vital for assessing risks on an individual basis and making well-informed clinical decisions.

FcRn regulates antigen presentation in dendritic cells downstream of DEC205-targeted vaccines.

Dendritic cell (DC)-targeted vaccination is a new mode of antigen delivery that relies on the use of monoclonal antibodies (mAb) to target antigen to specific DC subsets. The neonatal Fc receptor (FcRn) is a non-classical Fc receptor that binds to immunoglobulin G (IgG) in acidified endosomes and controls its intracellular transport and recycling. FcRn is known to participate in the antigen presentation of immune complexes, however its contribution to DC-targeted vaccination has not previously been examined. Here we have investigated the role of FcRn in antigen presentation using antigen conjugated to IgG mAb which target specific DC receptors, including DEC205 and Clec9A expressed by the conventional DC 1 (cDC1) subset. We show that FcRn is expressed at high levels by cDC1, both at steady-state and following activation and plays a significant role in MHC I cross-presentation and MHC II presentation of antigens that are targeted to cDC1 via mAb specific for DEC205. This effect of FcRn is intrinsic to cDC1 and FcRn impacts the efficacy of anti-DEC205-mediated vaccination against B cell lymphoma. In contrast, FcRn does not impact presentation of antigens targeted to Clec9A and does not regulate presentation of cell-associated antigen. These data highlight a new and unique role of FcRn in controlling the immunogenicity of anti-DEC205-based vaccination, with consequences for exploiting this pathway to improve DC-targeted vaccine outcomes.