Interfacial Micro-Environment of Electrocatalysis and Its Applications for Organic Electro-Oxidation Reaction.

Conventional designing principal of electrocatalyst is focused on the electronic structure tuning, on which effectively promotes the electrocatalysis. However, as a typical kind of electrode-electrolyte interface reaction, the electrocatalysis performance is also closely dependent on the electrocatalyst interfacial micro-environment (IME), including pH, reactant concentration, electric field, surface geometry structure, hydrophilicity/hydrophobicity, etc. Recently, organic electro-oxidation reaction (OEOR), which simultaneously reduces the anodic polarization potential and produces value-added chemicals, has emerged as a competitive alternative to oxygen evolution reaction, and the role IME played in OEOR is receiving great interest. Thus, this article provides a timely review on IME and its applications toward OEOR. In this review, the IME for conventional gas-involving reactions, as a contrast, is first presented, and then the recent progresses of IME toward diverse typical OEOR are summarized; especially, some representative works are thoroughly discussed. Additionally, cutting-edge analytical methods and characterization techniques are introduced to comprehensively understand the role IME played in OEOR. In the last section, perspectives and challenges of IME regulation for OEOR are shared.

Alantolactone enhances the sensitivity of melanoma to MAPK pathway inhibitors by targeting inhibition of STAT3 activation and down-regulating stem cell markers.

Mitogen-activated protein kinase inhibitors (MAPKi) were the first line drugs for advanced melanoma patients with BRAF mutation. Targeted therapies have significant therapeutic effects; however, drug resistance hinders their long-term efficacy. Therefore, the development of new therapeutic strategies against MAPKi resistance is critical. Our previous results showed that MAPKi promote feedback activation of STAT3 signaling in BRAF-mutated cancer cells. Studies have shown that alantolactone inhibited the activation of STAT3 in a variety of tumor cells. Our results confirmed that alantolactone suppressed cell proliferation and promoted apoptosis by inhibiting STAT3 feedback activation induced by MAPKi and downregulating the expression of downstream Oct4 and Sox2. The inhibitory effect of alantolactone combined with a MAPKi on melanoma cells was significantly stronger than that on normal cells. In vivo and in vitro experiments showed that combination treatment was effective against drug-resistant melanomas. Our research indicates a potential novel combination therapy (alantolactone and MAPKi) for patients with BRAF-mutated melanoma.

Identification of symptom clusters and sentinel symptoms during the first cycle of chemotherapy in patients with lung cancer.

PURPOSE: To identify symptom clusters (SCs) in patients with lung cancer who are undergoing initial chemotherapy and to identify the sentinel symptoms of each SC. METHODS: A convenience sampling method was used to recruit patients with lung cancer who were undergoing their initial chemotherapy treatment. Patient information was collected using the General Demographic Questionnaire, MD Anderson Symptom Inventory (including the lung cancer module) and a schedule documenting the initial occurrence of symptoms. The Walktrap algorithm was employed to identify SCs, while sentinel symptoms within each SC were identified using the Apriori algorithm in conjunction with the initial occurrence time of symptoms. RESULTS: A total of 169 patients with lung cancer participated in this study, and four SCs were identified: the psychological SC (difficulty remembering, sadness, dry mouth, numbness or tingling, and distress), somatic SC (pain, fatigue, sleep disturbance, and drowsiness), respiratory SC (coughing, expectoration, chest tightness, and shortness of breath), and digestive SC (nausea, poor appetite, constipation, vomiting, and weight loss). Sadness, fatigue, and coughing were identified as sentinel symptoms of the psychological, somatic, and respiratory SCs, respectively. However, no sentinel symptom was identified for the digestive SC. CONCLUSION: Patients with lung cancer who are undergoing chemotherapy encounter a spectrum of symptoms, often presenting as SCs. The sentinel symptom of each SC emerges earlier than the other symptoms and is characterized by its sensitivity, significance, and driving force. It serves as a vital indicator of the SC and assumes a sentry role. Targeting sentinel symptoms might be a promising strategy for determining the optimal timing of interventions and for mitigating or decelerating the progression of the other symptoms within the SC.

eIF6 Promotes Gastric Cancer Proliferation and Invasion by Regulating Cell Cycle.

OBJECTIVE: To investigate the role and function of eIF6 in gastric cancer (GC). METHODS: The expression level of eIF6 in GC tissues and normal tissues was detected in different high-throughput sequencing cohorts. Survival analysis, gene differential analysis, and enrichment analysis were performed in the TCGA cohort. Biological networks centered on eIF6 were constructed through two different databases. Immunohistochemistry (IHC) and Western blot were used to detect protein expression of eIF6, and qRT-PCR was used to detect eIF6 mRNA expression. The correlation between the expression of eIF6 in GC tissues and clinicopathological parameters of GC was analyzed. siRNA knockout of eIF6 was used to study the proliferation, migration, and invasion. The effects of eIF6 on cell cycle and Cyclin B1 were detected by flow cytometry and Western blot. RESULTS: eIF6 was significantly overexpressed in GC tissues and predicted poor prognosis. In addition, 113 differentially expressed genes were detected in cancer-related biological pathways and functions by differential analysis. Biological networks revealed interactions of genes and proteins with eIF6. The expression intensity of eIF6 in cancer tissues was higher than that in adjacent tissues (P = 0.0001), confirming the up-regulation of eIF6 expression in GC tissues. The expression level of eIF6 was statistically significant with pTNM stage (P = 0.006). siRNA knockout of eIF6 significantly reduced the proliferation, colony formation, migration, and invasion ability of GC cells. Silencing of eIF6 also inhibited the cell cycle of GC cells in G2/M phase and decreased the expression level of CyclinB1. CONCLUSION: Our study suggests that eIF6 is up-regulated in GC and may promote the proliferation, migration, and invasion of GC by regulating cell cycle.

Expression of Caudal-Type Homologous Transcription Factor-2 (CDX2) in Duodenal Carcinoma and its Relationship with Prognosis.

Objective: Caudal-type homologous transcription factor 2 (CDX2) has been shown to be associated with prognosis in colorectal cancer, with those with high expression having a good prognosis and those with low expression having a poor prognosis. As duodenal and colorectal cancers are similar in histological origin, we suspect that CDX2 expression in duodenal cancer may also be related to prognosis. Therefore, the aim of this study was to investigate the expression of CDX2 in duodenal cancer and its relationship with prognosis. Methods: We collected the clinical data and pathological sections of 61 patients diagnosed with duodenal cancer by histopathology or cytology at Shanghai Changhai Hospital, Naval Medical University, from November 2011 to December 2022. CDX2 expressionin in duodenal cancer was detected by immunohistochemical analysis (streptavidin-peroxidasemethod, SP). Survival analysis was conducted using the Kaplan-Meier method and the Log-rank test. Multivariate analysis was performed using the Cox regression analysis. Results: The positive rate of CDX2 in duodenal carcinoma was 78.7% (48/61). The positive rate of CDX2 expression in patients with stage I/II was higher than that in patients with stage III/IV (P < .05), and there was no correlation between CDX2 expression and gender, age, degree of differentiation, CEA and anemia (P > .05). Univariate analysis by Kaplan-Meier and Log-rank test showed that the expression of CDX2, degree of differentiation, TNM staging and CEA were associated with the prognosis of CDX2 in the negative and positive for the OS 21.6 months and 49.8 months, respectively (P = .015). The median OS of poorly differentiated patients and moderately/well-differentiated patients were 13 months and 82.5 months, respectively (P < .001). The median OS for Stage I/II and Stage III/IV patients was 72.3 and 13 months, respectively (P < .001). The median OS of CEA < 5 ug/L and ≥5 ug/L were 49.8 months and 9.4 months, respectively (P = .002). Age, gender and whether anemia were not associated with prognosis (P > .05). Multivariate analysis by Cox regression analysis showed that the expression of CDX2 (RR=2.697, 95%CI: 1.191-6.106, P = .017) was an independent prognostic factor of duodenal carcinoma. The results suggest that the expression of CDX2 in duodenal cancer is closely related to the prognosis. Those with positive expression have a better prognosis and those with negative expression have a worse prognosis. Conclusion: CDX2 serves as an autonomous prognostic determinant in individuals diagnosed with duodenal cancer. Notably, patients exhibiting positive CDX2 expression demonstrate a considerably improved prognosis compared to those with negative CDX2 expression. CDX2 may play an important role as an tumor suppressor gene in the development of duodenal cancer. CDX2 can be used as an important factor for evaluating the prognosis of patients with duodenal cancer, and it has the potential to be a target for duodenal cancer therapy.

Passive green space exposure leading to lower aggression: The mediating role of sense of control.

Green spaces, integral to natural environments, have been extensively studied for their positive impact on mental health, yet their influence on social behavior, particularly aggression, is less explored. While prior research has predominantly emphasized the effects of actively engaging with nature, the significant role of passive nature exposure-a more common daily occurrence-has often been overlooked. We conducted two studies to explore the influence of passive green space exposure on aggression and the mediating effect of the sense of control. Study 1 (N = 240) utilized a cross-sectional survey to assess the relationship between passive green space exposure, sense of control, and aggression. Study 2 (N = 260) employed a single-factor between-subjects experimental design to further explore these relationships in a controlled environment. The results from both studies indicated that passive green space exposure is negatively related to aggression, and that this relationship is partially mediated by an increased sense of control. Specifically, passive green space exposure was found to negatively predict aggression by bolstering individuals' sense of control. These findings underscore the potential of enhancing the sense of control through environmental factors like green spaces as an effective strategy to reduce aggression. This study enriches our understanding of the broader impacts of green spaces, extending beyond mental health to include social behaviors. We discussed both the theoretical and practical implications of our findings, highlighting how urban planning and environmental design can incorporate green spaces to foster community well-being and mitigate aggressive behaviors.

Unraveling the longitudinal relationships between connectedness to nature, depressive symptoms, and learning burnout in adolescents.

INTRODUCTION: Following the conservation of resource theory and natural stress reduction theory, the current study investigated mediated pathways, reverse mediated pathways, and reciprocal pathways between connectedness to nature, depressive symptoms, and adolescent learning burnout via a half-longitudinal analysis, and discussed gender differences in the three models. METHODS: Two waves of data were collected in December 2022 (T1) and June 2023 (T2) for this study. The sample consisted of 1092 Chinese adolescents (52.20% girls, Mage = 13.03, SD = 1.43). Semi-longitudinal analyses were conducted to examine the relationship between connectedness to nature, depressive symptoms, and adolescent academic burnout. RESULTS: The results indicated that connectedness to nature can serve as a positive resource to alleviate the levels of depressive symptoms among adolescents and thereby decrease learning burnout. However, the protective effect of connectedness to nature was smaller, and the decreasing effect of learning burnout on connectedness to nature was stronger than the alleviating effect of connectedness to nature on learning burnout. Additionally, the study found that depressive symptoms and academic burnout have a mutually reinforcing effect over time and that the effects of this interaction are more pronounced in females. CONCLUSIONS: The present study emphasizes the protective role of nature connectedness and the detrimental effects of learning burnout in adolescents.

Synthesis and Insecticidal Activity of Novel Anthranilic Diamide Insecticides Containing Indane and Its Analogs.

Diamide insecticides have always been a hot research topic in the field of pesticides. To further discover new compounds with high activity and safety, indane and its analogs were introduced into chlorantraniliprole, and a battery of chlorfenil derivatives, including indane and its analogs, were designed and prepared for biological testing. Their characterization and verification were carried out through nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). Biological detection showed that all the compounds exhibited good insecticidal activity against Mythimna separata. At 0.8 mg/L, the insecticidal activity of compound 8q against Mythimna separata was 80%, which was slightly better than that of chlorantraniliprole. The results of the structure-activity relationship (SAR) analysis indicated that the indane moiety had a significant effect on insecticidal activity, especially in the R-configuration. The results indicated that chlorantraniliprole derivatives containing indane groups could serve as pilot compounds for the further development of new insecticides.

Developing a psychological care competences framework for nurses in China: a mixed methods study.

BACKGROUND: With social transformation, rapid economic development and deepening awareness of psychological health in China, people's demand for psychological health services is becoming increasingly urgent. A key challenge for Chinese medical organizations is to train enough qualified psychological care nurses. A greater understanding of psychological care competences (PCC) can help in clinical nurse selection, training, and assessment. OBJECTIVE: To develop a PCC framework for Chinese nurses and obtain a consensus on the framework among experts. METHODS: A descriptive mixed methods study was designed consisting of a literature review and semi-structured interviews followed by three Delphi rounds. The experts (n = 16) involved were nurses, nursing managers and educators from nine Chinese provinces with a specific interest in psychological care. Descriptive statistics assisted in data analysis. RESULTS: Using the Iceberg Model as a theoretical foundation, five main dimensions and associated subdomains were integrated from 39 chosen articles. The semi-structured interviews with 24 nursing managers and nurses confirmed all of the themes from the literature review while generating new themes, both of which were incorporated into the initial PCC framework. After three Delphi rounds, the experts reached consensus on the PCC framework, including five domains (knowledge, skills, professional ethics, personal traits, internal motivations) and 22 subdomains with connotations. The response rate (RR) values for the three rounds of consultation were 80.00%, 87.50% and 92.86%, the composite reliability (Cr) values were 0.89-0.90, and the Kendall coordination coefficients were 0.155-0.200 (P < 0.05). CONCLUSIONS: On the basis of the Iceberg Model, literature review and qualitative research methods along with Delphi technique were used to develop a scientific and systematic PCC framework. The research methods were feasible and the results were reliable, thereby providing a basis for adopting this framework into nursing education. A formal assessment tool should be developed to test the PCC of nurses in clinical practice.

Adsorption behavior of lead, cadmium, and arsenic on manganese-modified biochar: competition and promotion.

Biochar adsorption of heavy metals has been a research hotspot, yet there has been limited reports on the effect of heavy metal interactions on adsorption efficiency in complex systems. In this study, the adsorbent was prepared by pyrolysis of rice straw loaded with manganese (BC-Mn). The interactions of Pb, Cd and As adsorption on BC-Mn were systematically studied. The results of the adsorption isotherms for the binary metal system revealed a competitive adsorption between Pb and Cd, resulting in decreased Pb (from 214.38 mg/g to 148.20 mg/g) and Cd (from 165.73 mg/g to 92.11 mg/g). A notable promotion occurred between As and Cd, showing an increase from 234.93 mg/g to 305.00 mg/g for As and 165.73 mg/g to 313.94 mg/g for Cd. In the ternary metal system, Pb inhibition did not counteract the promotion of Cd and As. Furthermore, the Langmuir isotherm effectively described BC-Mn's adsorption process in monometallic, binary, and ternary metal systems (R2 > 0.9294). Zeta and FTIR analyses revealed simultaneous competition between Pb and Cd for adsorption on BC-Mn's -OH sites. XPS analysis revealed that As adsorption by BC-Mn facilitated the conversion of MnO2 and MnO to MnOOH, resulting in increased hydroxyl radical production on BC-Mn's surface. Simultaneously, Cd combined with the adsorbed As to form ternary Cd-As-Mn complexes, which expedited the removal of Cd. These results help to provide theoretical support as well as technical support for the treatment of Pb-Cd-As contaminated wastewater.

Ferrihydrite transformation impacted by coprecipitation of lignin: Inhibition or facilitation?

Lignin is a common soil organic matter that is present in soils, but its effect on the transformation of ferrihydrite (Fh) remains unclear. Organic matter is generally assumed to inhibit Fh transformation. However, lignin can reduce Fh to Fe(II), in which Fe(II)-catalyzed Fh transformation occurs. Herein, the effects of lignin on Fh transformation were investigated at 75°C as a function of the lignin/Fh mass ratio (0-0.2), pH (4-8) and aging time (0-96 hr). The results of Fh-lignin samples (mass ratios = 0.1) aged at different pH values showed that for Fh-lignin the time of Fh transformation into secondary crystalline minerals was significantly shortened at pH 6 when compared with pure Fh, and the Fe(II)-accelerated transformation of Fh was strongly dependent on pH. Under pH 6, at low lignin/Fh mass ratios (0.05-0.1), the time of secondary mineral formation decreased with increasing lignin content. For high lignosulfonate-content material (lignin:Fh = 0.2), Fh did not transform into secondary minerals, indicating that lignin content plays a major role in Fh transformation. In addition, lignin affected the pathway of Fh transformation by inhibiting goethite formation and facilitating hematite formation. The effect of coprecipitation of lignin on Fh transformation should be useful in understanding the complex iron and carbon cycles in a soil environment.

A review on the transformation of birnessite in the environment: Implication for the stabilization of heavy metals.

Birnessite is ubiquitous in the natural environment where heavy metals are retained and easily transformed. The surface properties and structure of birnessite change with the changes in external environmental conditions, which also affects the fate of heavy metals. Clarifying the effect and mechanism of the birnessite phase transition process on heavy metals is the key to taking effective measures to prevent and control heavy metal pollution. Therefore, the four transformation pathways of birnessite are summarized first in this review. Second, the relationship between transformation pathways and environmental conditions is proposed. These relevant environmental conditions include abiotic (e.g., co-existing ions, pH, oxygen pressure, temperature, electric field, light, aging, pressure) and biotic factors (e.g., microorganisms, biomolecules). The phase transformation is achieved by the key intermediate of Mn(III) through interlayer-condensation, folding, neutralization-disproportionation, and dissolution-recrystallization mechanisms. The AOS (average oxidation state) of Mn and interlayer spacing are closely correlated with the phase transformation of birnessite. Last but not least, the mechanisms of heavy metals immobilization in the transformation process of birnessite are summed up. They involve isomorphous substitution, redox, complexation, hydration/dehydration, etc. The transformation of birnessite and its implication on heavy metals will be helpful for understanding and predicting the behavior of heavy metals and the crucial phase of manganese oxides/hydroxides in natural and engineered environments.

Transcriptome sequencing leads to an improved understanding of the infection mechanism of Alternaria solani in potato.

BACKGROUND: Alternaria solani (A. solani), the main pathogen of potato early blight, causes serious yield reductions every year. The application of fungicides is the most common and effective method of controlling Alternaria-caused diseases. The differentially expressed transcripts of A. solani infecting potato were identified, revealing a group of valuable candidate genes for a systematic analysis to increase the understanding of the molecular pathogenesis of A. solani, and providing scientific data for formulating additional measures to prevent and control potato early blight. In this study, a deep RNA-sequencing approach was applied to gain insights into A. solani pathogenesis. At 3, 4, and 5 days post inoculation (dpi), RNA samples from the susceptible potato cultivar Favorita infected with A. solani strain HWC-168, were sequenced and utilized for transcriptome analysis, and compared to the transcriptome obtained 0 dpi. RESULTS: A total of 4430 (2167 upregulated, 2263 downregulated), 4736 (2312 upregulated, 2424 downregulated), and 5043 (2411 upregulated, 2632 downregulated) genes were differentially expressed 3, 4 and 5 dpi, respectively, compared with genes analysed at 0 dpi. KEGG enrichment analysis showed that genes involved in the pathways of amino acid metabolism, glucose metabolism, and enzyme activity were significantly differentially expressed at the late infection stage. Correspondingly, symptoms developed rapidly during the late stage of A. solani infection. In addition, a short time-series expression miner (STEM) assay was performed to analyse the gene expression patterns of A. solani and Profile 17 and 19 showed significant change trends 3, 4 and 5 dpi. Both profiles, but especially Profile 17, included enzymes, including transferases, oxidoreductases, hydrolases and carbohydrate-active enzymes (CAZYmes), which may play important roles in late fungal infection. Furthermore, possible candidate effectors were identified through the adopted pipelines, with 137 differentially expressed small secreted proteins identified, including some enzymes and proteins with unknown functions. CONCLUSIONS: Collectively, the data presented in this study show that amino acid metabolism, and glucose metabolism pathways, and specific pathway-related enzymes may be key putative pathogenic factors, and play important roles in late stage A. solani infection. These results contribute to a broader base of knowledge of A. solani pathogenesis in potato, as indicated by the transcriptional level analysis, and provide clues for determining the effectors of A. solani infection.

Identification of a psychiatric risk gene NISCH at 3p21.1 GWAS locus mediating dendritic spine morphogenesis and cognitive function.

BACKGROUND: Schizophrenia and bipolar disorder (BD) are believed to share clinical symptoms, genetic risk, etiological factors, and pathogenic mechanisms. We previously reported that single nucleotide polymorphisms spanning chromosome 3p21.1 showed significant associations with both schizophrenia and BD, and a risk SNP rs2251219 was in linkage disequilibrium with a human specific Alu polymorphism rs71052682, which showed enhancer effects on transcriptional activities using luciferase reporter assays in U251 and U87MG cells. METHODS: CRISPR/Cas9-directed genome editing, real-time quantitative PCR, and public Hi-C data were utilized to investigate the correlation between the Alu polymorphism rs71052682 and NISCH. Primary neuronal culture, immunofluorescence staining, co-immunoprecipitation, lentiviral vector production, intracranial stereotaxic injection, behavioral assessment, and drug treatment were used to examine the physiological impacts of Nischarin (encoded by NISCH). RESULTS: Deleting the Alu sequence in U251 and U87MG cells reduced mRNA expression of NISCH, the gene locates 180 kb from rs71052682, and Hi-C data in brain tissues confirmed the extensive chromatin contacts. These data suggested that the genetic risk of schizophrenia and BD predicted elevated NISCH expression, which was also consistent with the observed higher NISCH mRNA levels in the brain tissues from psychiatric patients compared with controls. We then found that overexpression of NISCH resulted in a significantly decreased density of mushroom dendritic spines with a simultaneously increased density of thin dendritic spines in primary cultured neurons. Intriguingly, elevated expression of this gene in mice also led to impaired spatial working memory in the Y-maze. Given that Nischarin is the target of anti-hypertensive agents clonidine and tizanidine, which have shown therapeutic effects in patients with schizophrenia and patients with BD in preliminary clinical trials, we demonstrated that treatment with those antihypertensive drugs could reduce NISCH mRNA expression and rescue the impaired working memory in mice. CONCLUSIONS: We identify a psychiatric risk gene NISCH at 3p21.1 GWAS locus influencing dendritic spine morphogenesis and cognitive function, and Nischarin may have potentials for future therapeutic development.

Projected feature assisted coarse to fine point cloud registration method for large-size 3D measurement.

Fringe projection profilometry has gained significant interest due to its high precision, enhanced resolution, and simplified design. Typically, the spatial and perspective measurement capability is restricted by the lenses of the camera and projector in accordance with the principles of geometric optics. Therefore, large-size object measurement requires data acquisition from multiple perspectives, followed by point cloud splicing. Current point cloud registration methods usually rely on 2D feature textures, 3D structural elements, or supplementary tools, which will increase costs or limit the scope of the application. To address large-size 3D measurement more efficiently, we propose a low-cost and feasible method that combines active projection textures, color channel multiplexing, image feature matching and coarse-to-fine point registration strategies. Using a composite structured light with red speckle patterns for larger areas and blue sinusoidal fringe patterns for smaller ones, projected onto the surface, which allows us to accomplish simultaneous 3D reconstruction and point cloud registration. Experimental results demonstrate that the proposed method is effective for the 3D measurement of large-size and weak-textured objects.

Multispectral transparent electromagnetic-wave-absorbing optical window technology based on a random grid.

A multimode detection system has stringent requirements in terms of electromagnetic characteristic control and electromagnetic compatibility. To meet these requirements, we designed and manufactured a type of transparent electromagnetic-wave-absorbing optical window based on a random grid (EAOWRG) in this study. Owing to the design and regulation of the materials of the random grid and the structures of the metasurface, the optical window has excellent multispectral transparency, electromagnetic wave absorption, and electromagnetic shielding performance. The experimental results showed that the transmissivity of the EAOWRG in the optical spectral ranges of 460-800 nm and 8-12 µm is above 89.77%, the electromagnetic reflectivity in the frequency ranges of 3.6-7.2 GHz and 14.3-17.7 GHz is not more than - 5 dB, the bandwidth at which the electromagnetic reflectivity is not more than -10 dB is 4.4 GHz, the electromagnetic shielding effectiveness in the frequency range of 2-18 GHz is above 31 dB. The average radar cross section of the detection system using the EAOWRG in the ± 60° angle domain at 6 GHz is 8.79 dB lower than that before processing. The detection system has a good imaging effect in the visible and infrared bands, meeting the requirements of the electromagnetic characteristic control and electromagnetic compatibility, and has good application prospects.

Combined GFAP, NFL, Tau, and UCH-L1 panel increases prediction of outcomes in neonatal encephalopathy.

BACKGROUND: Neuroprognostication in neonates with neonatal encephalopathy (NE) may be enhanced by early serial measurement of a panel of four brain-specific biomarkers. METHODS: To evaluate serum biomarkers, 40 NE samples and 37 healthy neonates from a biorepository were analyzed. Blood samples were collected at 0-6, 12, 24, 48, and 96 h of life. MRI provided a short-term measure of injury. Long-term outcomes included death or a Bayley III score at 17-24 months of age. RESULTS: Glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase-L1 (UCH-L1), and Tau peaked at 0-6 h of life, while neurofilament light chain (NFL) peaked at 96 h of life. These four marker concentrations at 96 h of life differentiated moderate/severe from none/mild brain injury by MRI, while GFAP and Tau showed early discrimination. For long-term outcomes, GFAP, NFL, Tau, and UCH-L1 could differentiate a poor outcome vs good outcome as early as 0-6 h of life, depending on the Bayley domain, and a combination of the four markers enhanced the sensitivity and specificity. Machine learning trajectory analyses identified upward trajectory patients with a high concordance to poor outcomes. CONCLUSION: GFAP, NFL, Tau, and UCH-L1 may be of neuroprognostic significance after NE. IMPACT: Serial measurements of GFAP, NFL, Tau, and UCH-L1 show promise in aiding the bedside clinician in making treatment decisions in neonatal encephalopathy. The panel of four neuroproteins increased the ability to predict neurodevelopmental outcomes. The study utilized a trajectory analysis that enabled predictive modeling. A panel approach provides the bedside clinician with objective data to individualize care. This study provides the foundation to develop a point of care device in the future.

Analysis of Cytological Misdiagnosis and Oversight of Adenoid Cystic Carcinoma of Salivary Gland.

OBJECTIVE: In this article on adenoid cystic carcinoma (ACC) of salivary gland, we intend to summarize the causes of misdiagnosis and oversight of ACC hoping to improve cytological diagnostic accuracy, clinical management and patient treatment. METHODS: The study retrospectively reviewed 32 patients with ACC of salivary gland, registered at the Affiliated Hospital of Southwest Medical University from July 2014 to June 2021. These cases were diagnosed by FNA and surgical excision biopsy. All cytopathological results were retrospectively categorized according to Milan system for reporting salivary gland cytopathology (MSRSGC). The accuracy of FNA was verified by surgical excision biopsy. RESULTS: Of these 32 patients, 16 (50.0%) cases were male, and 16 (50.0%) were female. Their age ranged from 21 to 79 years, with an average age of 50.32 years. The highest incidence (15/32, 46.9%) of ACC was observed in patients between 41 and 50 years of age. 10 cases (31.3%) occurred in the parotid gland, 9 cases (28.1%) in the submandibular gland, 9 cases (28.1%) in the sublingual gland, 3 cases (9.4%) in the palate, and 1 case (3.1%) in the lip. Among the 32 cases of ACC, 23 cases (71.9%) were classified to VI, 4 cases (12.5%) to IVa, and 5 cases (15.6%) to II by MSRSGC. A comparison of the FNA results with biopsy showed that the accuracy of FNA in ACC of salivary gland is 71.9%. Being able to identify the cytomorphological features is the key factor for accurate diagnosis of ACC of the salivary gland. CONCLUSION: Our results confirm that FNA is an important initial screening in the diagnosis of ACC of salivary gland. Increased study of the cytomorphology of ACC is beneficial for more accurate diagnosis of ACC, to reduce misdiagnosis and oversight.

Complex Autoantibody Responses Occur following Moderate to Severe Traumatic Brain Injury.

Most of the variation in outcome following severe traumatic brain injury (TBI) remains unexplained by currently recognized prognostic factors. Neuroinflammation may account for some of this difference. We hypothesized that TBI generated variable autoantibody responses between individuals that would contribute to outcome. We developed a custom protein microarray to detect autoantibodies to both CNS and systemic Ags in serum from the acute-phase (the first 7 d), late (6-12 mo), and long-term (6-13 y) intervals after TBI in human patients. We identified two distinct patterns of immune response to TBI. The first was a broad response to the majority of Ags tested, predominantly IgM mediated in the acute phase, then IgG dominant at late and long-term time points. The second was responses to specific Ags, most frequently myelin-associated glycopeptide (MAG), which persisted for several months post-TBI but then subsequently resolved. Exploratory analyses suggested that patients with a greater acute IgM response experienced worse outcomes than predicted from current known risk factors, suggesting a direct or indirect role in worsening outcome. Furthermore, late persistence of anti-MAG IgM autoantibodies correlated with raised serum neurofilament light concentrations at these time points, suggesting an association with ongoing neurodegeneration over the first year postinjury. Our results show that autoantibody production occurs in some individuals following TBI, can persist for many years, and is associated with worse patient outcome. The complexity of responses means that conventional approaches based on measuring responses to single antigenic targets may be misleading.

Intervention of Tanshinone IIA on the PGK1-PDHK1 Pathway to Reprogram Macrophage Phenotype After Myocardial Infarction.

BACKGROUND: Myocardial infarction remains a disease with high morbidity and death rate among cardiovascular diseases. Macrophages are abundant immune cells in the heart. Under different stimulatory factors, macrophages can differentiate into different phenotypes and play a dual pro-inflammatory and anti-inflammatory role. Therefore, a potential strategy for the treatment of myocardial infarction is to regulate the energy metabolism of macrophages and thereby regulate the polarization of macrophages. Tan IIA is an effective liposolubility component extracted from the root of Salvia miltiorrhiza and plays an important role in the treatment of cardiovascular diseases. On this basis, this study proposed whether Tan IIA could affect phenotype changes by regulating energy metabolism of macrophages, and thus exert its potential in the treatment of MI. METHODS: Establishing a myocardial infarction model, Tan IIA was given for 3 days and 7 days for intervention. Cardiac function was detected by echocardiography, and cardiac pathological sections of each group were stained with HE and Masson to observe the inflammatory cell infiltration and fibrosis area after administration. The expression and secretion of inflammatory factors in heart tissue and serum of each group, as well as the proportion of macrophages at the myocardial infarction site, were detected using RT-PCR, ELISA, and immunofluorescence. The mitochondrial function of macrophages was evaluated using JC-1, calcium ion concentration detection, reactive oxygen species detection, and mitochondrial electron microscopic analysis. Mechanically, single-cell transcriptome data mining, cell transcriptome sequencing, and molecular docking technology were used to anchor the target of Tan IIA and enrich the pathways to explore the mechanism of Tan IIA regulating macrophage energy metabolism and phenotype. The target of Tan IIA was further determined by gene knockdown and overexpression assay. RESULTS: The intervention of Tan IIA can improve the cardiac function, inflammatory cell infiltration and fibrosis after MI, reduce the expression of inflammatory factors in the heart, enhance the secretion of anti-inflammatory factors, increase the proportion of M2-type macrophages, reduce the proportion of M1-type macrophages, and promote tissue repair, suggesting that Tan IIA has pharmacological effects in the treatment of MI. In terms of mechanism, RNA-seq results suggest that the phenotype of macrophages is strongly correlated with energy metabolism, and Tan IIA can regulate the PGK1-PDHK1 signaling pathway, change the energy metabolism mode of macrophages, and then affect its phenotype. CONCLUSION: Tan IIA regulates the energy metabolism of macrophages and changes its phenotype through the PGK1-PDHK1 signaling pathway, thus playing a role in improving MI.