The value of combined detection D-dimer and NLR in judging the severity and short-term prognosis of acute cardiogenic cerebral embolism in elderly patients.

OBJECTIVE: To assess the utility of combined neutrophil-to-lymphocyte ratio (NLR) and D-dimer detection in determining the severity and short-term prognosis of acute cardiogenic cerebral embolism in older adults. METHODS: A total of 202 elderly patients with NVAF who were hospitalized in the Third Affiliated Hospital of Anhui Medical University from April 1, 2020, to April 1, 2023, were selected and divided into the observation group (69 patients with NVAF combined with ACCE) and the control group (133 patients with NVAF alone) according to whether they had acute cardiogenic cerebral embolism. According to the National Institutes of Health Stroke Scale (NIHSS), the observation group was divided into mild, moderate, and severe cerebral infarction groups: 26 cases (MICI group), 29 cases (MOCI group) and 14 cases (SCI group), respectively. According to the modified Rankin scale (mRS) after 3 months, 30 cases were divided into the good prognosis group and 39 cases were divided into the poor prognosis group. The D-dimer and NLR levels were detected in the two groups. Logistic regression was used to analyze whether the two factors were factors affecting the short-term prognosis of patients with acute cardiogenic cerebral embolism, and the ROC curve was drawn to evaluate the value of the two combined tests on the short-term prognosis of patients with acute cardiogenic cerebral embolism RESULTS: The levels of D-dimer and NLR in peripheral blood in SCI group [1.82 (0.68-6.71) mg/l, 4.55 (2.31-6.68)] were higher than those in MOCI group [1.16 (0.65-1.90) mg/l, 3.84 (3.14-6.87)] and MICI group [0.53(0.32-0.90) mg/l, 2.46(2.09-3.79)]; The difference between groups was statistically significant (P<0.05). Logistic regression analysis showed that D-dimer and NLR were independent risk factors for poor prognosis in patients with acute cardiogenic cerebral embolism (OR values were 1.772 and 1.603, and 95%CI were 1.060-2.963 and 1.100-2.338, respectively, both P<0.05). The AUC of D-dimer combined with NLR for predicting poor prognosis of acute cardiogenic cerebral embolism was 0.812, which is better than D-dimer and NLR alone. CONCLUSION: Peripheral blood D-dimer combined with NLR detection is helpful for the risk stratification and short-term prognosis assessment of patients with acute cardiogenic cerebral embolism. Clinical detection is of great significance for the prevention and monitoring of disease development.

Bafi A1 inhibits nano-copper oxide-induced mitochondrial damage by reducing the release of copper from lysosomes.

This study demonstrated that both copper oxide nanoparticles (CuO-NPs) and copper nanoparticles (Cu-NPs) can cause swelling, inflammation, and cause damage to the mitochondria of alveolar type II epithelial cells in mice. Cellular examinations indicated that both CuO-NPs and Cu-NPs can reduce cell viability and harm the mitochondria of human bronchial epithelial cells, particularly Beas-2B cells. However, it is clear that CuO-NPs exhibit a more pronounced detrimental effect compared with Cu-NPs. Using bafilomycin A1 (Bafi A1), an inhibitor of lysosomal acidification, was found to enhance cell viability and alleviate mitochondrial damage caused by CuO-NPs. Additionally, Bafi A1 also reduces the accumulation of dihydrolipoamide S-acetyltransferase (DLAT), a marker for mitochondrial protein toxicity, induced by CuO-NPs. This observation suggests that the toxicity of CuO-NPs depends on the distribution of copper particles within cells, a process facilitated by the acidic environment of lysosomes. The release of copper ions is thought to be triggered by the acidic conditions within lysosomes, which aligns with the lysosomal Trojan horse mechanism. However, this association does not seem to be evident with Cu-NPs.

Novel insights into immune-related genes associated with type 2 diabetes mellitus-related cognitive impairment.

BACKGROUND: The cognitive impairment in type 2 diabetes mellitus (T2DM) is a multifaceted and advancing state that requires further exploration to fully comprehend. Neuroinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the disease. AIM: To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment. METHODS: To identify differentially expressed genes (DEGs) between T2DM and controls, we used data from the Gene Expression Omnibus database GSE125387. To identify T2DM module genes, we used Weighted Gene Co-Expression Network Analysis. All the genes were subject to Gene Set Enrichment Analysis. Protein-protein interaction network construction and machine learning were utilized to identify three hub genes. Immune cell infiltration analysis was performed. The three hub genes were validated in GSE152539 via receiver operating characteristic curve analysis. Validation experiments including reverse transcription quantitative real-time PCR, Western blotting and immunohistochemistry were conducted both in vivo and in vitro. To identify potential drugs associated with hub genes, we used the Comparative Toxicogenomics Database (CTD). RESULTS: A total of 576 DEGs were identified using GSE125387. By taking the intersection of DEGs, T2DM module genes, and immune-related genes, a total of 59 genes associated with the immune system were identified. Afterward, machine learning was utilized to identify three hub genes (H2-T24, Rac3, and Tfrc). The hub genes were associated with a variety of immune cells. The three hub genes were validated in GSE152539. Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro, consistent with the bioinformatics analysis. Additionally, 11 potential drugs associated with RAC3 and TFRC were identified based on the CTD. CONCLUSION: Immune-related genes that differ in expression in the hippocampus are closely linked to microglia. We validated the expression of three hub genes both in vivo and in vitro, consistent with our bioinformatics results. We discovered 11 compounds associated with RAC3 and TFRC. These findings suggest that they are co-regulatory molecules of immunometabolism in diabetic cognitive impairment.

Case report: Cutaneous anthrax diagnosed using mNGS of a formalin-fixed paraffin-embedded tissue sample.

The metagenomic next-generation sequencing (mNGS) method is preferred for genotyping useful for the identification of organisms, illumination of metabolic pathways, and determination of microbiota. It can accurately obtain all the nucleic acid information in the test sample. Anthrax is one of the most important zoonotic diseases, infecting mainly herbivores and occasionally humans. The disease has four typical clinical forms, cutaneous, gastrointestinal, inhalation, and injection, all of which may result in sepsis or meningitis, with cutaneous being the most common form. Here, we report a case of cutaneous anthrax diagnosed by mNGS in a butcher. Histopathology of a skin biopsy revealed PAS-positive bacilli. Formalin-fixed paraffin-embedded (FFPE) tissue sample was confirmed the diagnosis of anthrax by mNGS. He was cured with intravenous penicillin. To our knowledge, this is the first case of cutaneous anthrax diagnosed by mNGS using FFPE tissue. mNGS is useful for identifying pathogens that are difficult to diagnose with conventional methods, and FFPE samples are simple to manage. Compared with traditional bacterial culture, which is difficult to cultivate and takes a long time, mNGS can quickly and accurately help us diagnose anthrax, so that anthrax can be controlled in a timely manner and prevent the outbreak of epidemic events.

CaMK4: Structure, physiological functions, and therapeutic potential.

Calcium/calmodulin-dependent protein kinase IV (CaMK4) is a versatile serine/threonine kinase involved in various cellular functions. It regulates T-cell differentiation, podocyte function, tumor cell proliferation/apoptosis, ß cell mass, and insulin sensitivity. However, the underlying molecular mechanisms are complex and remain incompletely understood. The aims of this review are to highlight the latest advances in the regulatory mechanisms of CaMK4 underlying T-cell imbalance and parenchymal cell mass in multiple diseases. The structural motifs and activation of CaMK4, as well as the potential role of CaMK4 as a novel therapeutic target are also discussed.

Synthesis of N-doped and P-doped silicon quantum dots and their applications for tetracycline detection in the honey samples and antibacterial properties.

The abuse of tetracycline can lead to its residue in animal derived foods, posing many potential hazards to human health. Therefore, rapid and accurate detection of tetracycline is an important means to ensure food safety. Nitrogen doped and phosphorus doped silicon quantum dots (N-SiQDs, P-SiQDs) with remarkable optical stability were fabricated via a one-pot hydrothermal procedure in this study. Upon the excitation at 346 nm, N-SiQDs and P-SiQDs emitted fluorescence at 431 nm and 505 nm, respectively. Two SiQDs had the potential to serve as a probe for detecting low concentrations of tetracycline (TC), employing a mechanism of the static quenching effect. The calibration curves of N-SiQDs and P-SiQDs were linear within the range of 0-0.8 µM and 0-0.4 µM, the limits of detection were low as 5.35 × 10-4 µmol/L and 6.90 × 10-3 µmol/L, respectively. This method could be used successfully to detect TC in honey samples. Moreover, the remarkable antibacterial efficacy of two SiQDs could be attributed to the generation of a large number of intracellular reactive oxygen species. The SEM images showed that the structure of bacterial cell was disrupted and the surface became irregular when treated with both SiQDs. These properties enabled potential usage of SiQDs as excellent antibacterial material for different biomedical applications.

Electrolyte Design with Dual -C≡N Groups Containing Additives to Enable High-Voltage Na3V2(PO4)2F3-Based Sodium-Ion Batteries.

Na3V2(PO4)2F3 is recognized as a promising cathode for high energy density sodium-ion batteries due to its high average potential of ∼3.95 V (vs Na/Na+). A high-voltage-resistant electrolyte is of high importance due to the long duration of 4.2 V (vs Na/Na+) when improving cyclability. Herein, a targeted electrolyte containing additives with two -C≡N groups like succinonitrile has been designed. In this design, one -C≡N group is accessible to the solvation sheath and enables the other -C≡N in dinitrile being exposed and subsequently squeezed into the electric double layer. Then, the squeezed -C≡N group is prone to a preferential adsorption on the electrode surface prior to the exposed -CH2/-CH3 in Na+-solvent and oxidized to construct a stable and electrically insulating interface enriched CN-/NCO-/Na3N. The Na3V2(PO4)2F3-based sodium-ion batteries within a high-voltage of 2-4.3 V (vs Na/Na+) can accordingly achieve an excellent cycling stability (e.g., 95.07% reversible capacity at 1 C for 1,5-dicyanopentane and 98.4% at 2 C and 93.0% reversible capacity at 5 C for succinonitrile after 1000 cycles). This work proposes a new way to design high-voltage electrolytes for high energy density sodium-ion batteries.

Enhancing the evaluation of acute ischemic stroke risk in individuals with non-valvular atrial fibrillation by including laboratory indicators.

To investigate the clinical significance of the CHA2DS2-VASc-60 score, lipoprotein (a) [Lp(a)], red blood cell distribution width (RDW), and their combined effect in patients with non-valvular atrial fibrillation (NVAF) who experience acute ischemic stroke (AIS). This retrospective analysis was conducted on the clinical data of hospitalized patients with NVAF at the Third Affiliated Hospital of Anhui Medical University between April 1, 2020, and April 1, 2023. Based on the diagnosis of acute ischemic stroke (AIS), the patients were divided into two groups: the AIS group (150 cases of NVAF patients with comorbid AIS) and the non-AIS group (163 cases of NVAF patients without AIS). We performed CHA2DS2-VASc-60 scoring for all patients and collected their laboratory indicators and echocardiographic indicators during hospitalization. The study comprised 313 individuals with NVAF in total. There is a statistically significant difference (P < 0.05) in the comparison of CHA2DS2-VASc-60 score (5.68 ± 1.12 vs. 3.67 ± 1.47), Lp(a) [23.98 (13.28, 42.22) vs. 14.32 (7.96, 21.91)] and RDW (13.67 ± 1.25 vs. 12.94 ± 0.76) between NVAF patients with and without concomitant AIS. The results of the Spearman correlation analysis demonstrate a positive association between Lp(a) and RDW levels and both the CHA2DS2-VASc score and the CHA2DS2-VASc-60 score in patients with NVAF. Multivariate logistic regression analysis revealed that CHA2DS2-VASc-60 score [OR = 6.549, 95% CI: 4.110-10.433, P < 0.05], Lp(a) [OR = 1.023, 95% CI: 1.005-1.041, P < 0.05], and RDW [OR = 1.644, 95% CI: 1.071-2.525, P < 0.05] were independent risk factors for AIS in patients with non-valvular atrial fibrillation (NVAF). The receiver operator characteristic (ROC) curves showed that the area under the curve of CHA2DS2-VASc-60 score, Lp(a), RDW, and CHA2DS2-VASc-60 score combined with Lp(a) and RDW predicted that NVAF patients with AIS were 0.881 [95% CI: 0.804-0.906], 0.685 [95% CI: 0.626-0.744], 0.695 [95% CI: 0.637-0.754], and 0.906 [95% CI: 0.845-0.921], respectively. The CHA2DS2-VASc-60 score, Lp(a), and RDW were significantly increased in NVAF patients with AIS, which were independent risk factors for NVAF patients with AIS. The combination of the three has a high predictive capacity for NVAF patients with AIS.

Expression and function of VISTA on myeloid cells.

V-domain containing Ig Suppressor of T cell Activation (VISTA) is predominantly expressed on myeloid cells and functions as a ligand/receptor/soluble molecule. In inflammatory responses and immune responses, VISTA regulates multiple functions of myeloid cells, such as chemotaxis, phagocytosis, T cell activation. Since inflammation and immune responses are critical in many diseases, VISTA is a promising therapeutic target. In this review, we will describe the expression and function of VISTA on different myeloid cells, including neutrophils, monocytes, macrophages, dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs). In addition, we will discuss whether the functions of VISTA on these cells impact the disease processing.

A cross-cultural examination of temporal orientation through everyday language on social media.

Past research has shown that culture can form and shape our temporal orientation-the relative emphasis on the past, present, or future. However, there are mixed findings on how temporal orientations vary between North American and East Asian cultures due to the limitations of survey methodology and sampling. In this study, we applied an inductive approach and leveraged big data and natural language processing between two popular social media platforms-Twitter and Weibo-to assess the similarities and differences in temporal orientation in the United States of America and China, respectively. We first established predictive models from annotation data and used them to classify a larger set of English Twitter sentences (NTW = 1,549,136) and a larger set of Chinese Weibo sentences (NWB = 95,181) into four temporal catetories-past, future, atemporal present, and temporal present. Results show that there is no significant difference between Twitter and Weibo on past or future orientations; the large temporal orientation difference between North Americans and Chinese derives from their different prevailing focus on atemporal (e.g., facts, ideas) present (Twitter) or temporal present (e.g., the "here" and "now") (Weibo). Our findings contribute to the debate on cultural differences in temporal orientations with new perspectives following a new methodological approach. The study's implications call for a reevaluation of how temporal orientation is measured in cross-cultural studies, emphasizing the use of large-scale language data and acknowledging the atemporal present category. Understanding temporal orientations can guide effective cross-cultural communication strategies to tailor approaches for different audience based on temporal orientations, enhancing intercultural understanding and engagement.

Metagenomic analysis of individual mosquito viromes reveals the geographical patterns and drivers of viral diversity.

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Here, using a meta-transcriptomic approach, we determined the viromes of 2,438 individual mosquitoes (81 species), spanning ~4,000 km along latitudes and longitudes in China. From these data we identified 393 viral species associated with mosquitoes, including 7 (putative) species of arthropod-borne viruses (that is, arboviruses). We identified potential mosquito species and geographic hotspots of viral diversity and arbovirus occurrence, and demonstrated that the composition of individual mosquito viromes was strongly associated with host phylogeny. Our data revealed a large number of viruses shared among mosquito species or genera, enhancing our understanding of the host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, perhaps reflecting long-distance mosquito dispersal. Together, these results greatly expand the known mosquito virome, linked viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the biogeography and diversity of viruses in insect vectors.

Association of sleep characteristics with cardiovascular disease risk in adults over 40 years of age: a cross-sectional survey.

Background: The relationship between sleep characteristics and cardiovascular disease (CVD) risk has yet to reach a consistent conclusion, and more research needs to be carried out. This study aimed to explore the relationship between snoring, daytime sleepiness, bedtime, sleep duration, and high-risk sleep patterns with CVD risk. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2015-2018 were collected and analyzed. Multivariable logistic regression was used to evaluate the relationship between snoring, daytime sleepiness, bedtime, sleep duration, high-risk sleep patterns, and CVD risk. Stratified analysis and interaction tests were carried out according to hypertension, diabetes and age. Results: The final analysis contained 6,830 participants, including 1,001 with CVD. Multivariable logistic regression suggested that the relationship between snoring [OR = 7.37,95%CI = (6.06,8.96)], daytime sleepiness [OR = 11.21,95%CI = (9.60,13.08)], sleep duration shorter than 7 h [OR = 9.50,95%CI = (7.65,11.79)] or longer than 8 h [OR = 6.61,95%CI = (5.33,8.19)], bedtime after 0:00 [OR = 13.20,95%CI = (9.78,17.80)] compared to 22:00-22:59, high-risk sleep patterns [OR = 47.73,95%CI = (36.73,62.04)] and CVD risk were statistically significant. Hypertension and diabetes interacted with high-risk sleep patterns, but age did not. Conclusions: Snoring, daytime sleepiness, excessive or short sleep duration, inappropriate bedtime, and high-risk sleep patterns composed of these factors are associated with the CVD risk. High-risk sleep patterns have a more significant impact on patients with hypertension and diabetes.

MnO2 porous carbon composite from cellulose enabling high gravimetric/volumetric performance for supercapacitor.

Preparing electrode material integrated with high gravimetric/volumetric capacitance and fast electron/ion transfer is crucial for the practical application. Owing to the structural contradiction, it is a big challenge to construct electrode material with high packing density, sufficient ion transport channels, and fast electronic transfer pathways. Herein, MnO2 porous carbon composite with abundant porous structure and 3D carbon skeleton was facilely fabricated from Linum usitatissimum. L stems via NaOH activation and MnO2 introduction. The in-situ introduced MnO2 not only increases the packing density and the electrical conductivity of the porous carbon but also provides more active sites for oxidation reactions. These unique characteristics endow the resultant MnO2 porous carbon composite with remarkable gravimetric capacitance of 549 F g-1, volumetric capacitance of 378 F cm-3, and capacitance retention of 54.9 %. Giving the simple process and low cost, this work might offer a new approach for structural design and the practical application of high-performance electrode materials.

The prognosis of haploidentical hematopoietic stem cell transplantation in infants and patients under 3 years old with acute leukemia.

BACKGROUND: The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients <3 years of age remains controversial. Data on haploidentical donor (HID) transplants in this age group is limited. PATIENTS AND METHODS: We retrospectively analyzed the prognosis of 97 patients with acute leukemia aged <3 years who underwent HID transplantation at our institute. RESULTS: With a median follow-up of 45 months, the 3-year disease-free survival (DFS), overall survival (OS), and 3-year cumulative incidence rate of treatment-related mortality were 69.3% (95% confidence interval (CI): 59.9%-78.7%), 74.2% (95% CI: 65.2%-83.2%), and 3.6% (95% CI: 0.9%-9.7%) in all 97 patients, respectively. The 3-year DFS and OS rate in patients diagnosed <1 year and patients diagnosed ≥1 year were comparable: 77.8% (95% CI: 62.2%-93.4%) versus 66.3% (95% CI: 55.0%-77.6%, p = .253) and 82.5% (95% CI: 66.3-98.7%) versus 72.8% (95% CI: 61.9%-83.7%, p = .153), respectively. At the last follow-up, 23 patients had died, and 20 had died of relapse. Multivariate analysis revealed that positive pre-HSCT flow cytometric minimal residual disease (hazard ratio 5.605, p = .000) and AML-M7 expression (hazard ratio 2.906, p = .014) were independent adverse prognostic variables for relapse. CONCLUSIONS: HID transplantation is potent and safe for infants and young patients with acute leukemia. Relapse is the primary cause of treatment failure.

Progress in Microbial Fertilizer Regulation of Crop Growth and Soil Remediation Research.

More food is needed to meet the demand of the global population, which is growing continuously. Chemical fertilizers have been used for a long time to increase crop yields, and may have negative effect on human health and the agricultural environment. In order to make ongoing agricultural development more sustainable, the use of chemical fertilizers will likely have to be reduced. Microbial fertilizer is a kind of nutrient-rich and environmentally friendly biological fertilizer made from plant growth-promoting bacteria (PGPR). Microbial fertilizers can regulate soil nutrient dynamics and promote soil nutrient cycling by improving soil microbial community changes. This process helps restore the soil ecosystem, which in turn promotes nutrient uptake, regulates crop growth, and enhances crop resistance to biotic and abiotic stresses. This paper reviews the classification of microbial fertilizers and their function in regulating crop growth, nitrogen fixation, phosphorus, potassium solubilization, and the production of phytohormones. We also summarize the role of PGPR in helping crops against biotic and abiotic stresses. Finally, we discuss the function and the mechanism of applying microbial fertilizers in soil remediation. This review helps us understand the research progress of microbial fertilizer and provides new perspectives regarding the future development of microbial agent in sustainable agriculture.

Association between different insulin resistance surrogates and all-cause mortality in patients with coronary heart disease and hypertension: NHANES longitudinal cohort study.

BACKGROUND: Studies on the relationship between insulin resistance (IR) surrogates and long-term all-cause mortality in patients with coronary heart disease (CHD) and hypertension are lacking. This study aimed to explore the relationship between different IR surrogates and all-cause mortality and identify valuable predictors of survival status in this population. METHODS: The data came from the National Health and Nutrition Examination Survey (NHANES 2001-2018) and National Death Index (NDI). Multivariate Cox regression and restricted cubic splines (RCS) were performed to evaluate the relationship between homeostatic model assessment of IR (HOMA-IR), triglyceride glucose index (TyG index), triglyceride glucose-body mass index (TyG-BMI index) and all-cause mortality. The recursive algorithm was conducted to calculate inflection points when segmenting effects were found. Then, segmented Kaplan-Meier analysis, LogRank tests, and multivariable Cox regression were carried out. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the differentiation and accuracy of IR surrogates in predicting the all-cause mortality. Stratified analysis and interaction tests were conducted according to age, gender, diabetes, cancer, hypoglycemic and lipid-lowering drug use. RESULTS: 1126 participants were included in the study. During the median follow-up of 76 months, 455 participants died. RCS showed that HOMA-IR had a segmented effect on all-cause mortality. 3.59 was a statistically significant inflection point. When the HOMA-IR was less than 3.59, it was negatively associated with all-cause mortality [HR = 0.87,95%CI (0.78, 0.97)]. Conversely, when the HOMA-IR was greater than 3.59, it was positively associated with all-cause mortality [HR = 1.03,95%CI (1.00, 1.05)]. ROC and calibration curves indicated that HOMA-IR was a reliable predictor of survival status (area under curve = 0,812). No interactions between HOMA-IR and stratified variables were found. CONCLUSION: The relationship between HOMA-IR and all-cause mortality was U-shaped in patients with CHD and hypertension. HOMA-IR was a reliable predictor of all-cause mortality in this population.

Construction of molecular subtype model of osteosarcoma based on endoplasmic reticulum stress and tumor metastasis-related genes.

Introduction: Osteosarcoma, the prevailing primary bone malignancy among children and adolescents, is frequently associated with treatment failure primarily due to its pronounced metastatic nature. Methods: This study aimed to establish potential associations between hub genes and subtypes for the treatment of metastatic osteosarcoma. Differentially expressed genes were extracted from patients diagnosed with metastatic osteosarcoma and a control group of non-metastatic patients, using the publicly available gene expression profile (GSE21257). The intersection of these gene sets was determined by focusing on endoplasmic reticulum (ER) stress-related genes sourced from the GeneCards database. We conducted various analytical techniques, including functional and pathway enrichment analysis, WGCNA analysis, protein-protein interaction (PPI) network construction, and assessment of immune cell infiltration, using the intersecting genes. Through this analysis, we identified potential hub genes. Results: Osteosarcoma subtype models were developed using molecular consensus clustering analysis, followed by an examination of the associations between each subtype and hub genes. A total of 138 potential differentially expressed genes related to endoplasmic reticulum (ER) stress were identified. These genes were further investigated using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) pathways. Additionally, the PPI interaction network revealed 38 interaction relationships among the top ten hub genes. The findings of the analysis revealed a strong correlation between the extent of immune cell infiltration and both osteosarcoma metastasis and the expression of hub genes. Notably, the differential expression of the top ten hub genes was observed in osteosarcoma clusters 1 and 4, signifying their significant association with the disease. Conclusion: The identification of ten key genes linked to osteosarcoma metastasis and endoplasmic reticulum stress bears potential clinical significance. Additionally, exploring the molecular subtype of osteosarcoma has the capacity to guide clinical treatment decisions, necessitating further investigations and subsequent clinical validations.

WEE1 Inhibitors Mediate Antitumor Effects on Endometrial Cancer through Activation of Innate Immune Responses.

Introduction: Recurrence signifies the primary mortality factor in patients suffering from endometrial cancer, with few efficacious treatments currently available for recurrent cases. This research investigates the anti-tumoral capacities of WEE1 inhibitors within the context of endometrial cancer, aiming to establish a novel therapeutic avenue for high recurrence-risk patients. Materials and methods: We evaluated WEE1 expression in endometrial cancer patients utilizing immunohistochemistry on paraffin-embedded tissue sections. The cytotoxic potential of WEE1 inhibitors on endometrial cancer cells was assessed by CCK8 assay. Assays to gauge the influence of WEE1 inhibitors on cell proliferation and migration included clonal proliferation, wound healing, and transwell assays. We determined the impacts on apoptosis and cell cycle stages by flow cytometry. Employing qRT-PCR and western blotting, we investigated the mechanistic pathways underlying the anti-tumoral activity of WEE1 inhibitors. In vivo evaluations were executed to ascertain the inhibitory effect of WEE1 inhibitors on tumor growth in mice. Results: WEE1 exhibited high-level expression in endometrial cancer tissues, particularly pronounced in recurrent compared with non-recurrent patients. WEE1 inhibitors effectively eliminated endometrial cancer cells while inhibiting their proliferation and migration. Flow cytometric analyses revealed a significant promotion of apoptosis and an increase in G2/M phase cell proportion upon WEE1 inhibitor treatment. qRT-PCR and western blotting elucidated that WEE1 inhibitors activated the innate immune signaling pathway in endometrial cancer cells. Furthermore, in vivo assessments demonstrated substantial tumor growth suppression due to WEE1 inhibitors. Conclusions: WEE1 inhibitors initiated an innate immune response in endometrial cancer, exhibiting considerable anti-tumoral effects, which was promising for postoperative treatment of endometrial cancer, especially recurrent endometrial cancer patients.

Corticotropin-releasing hormone neurons control trigeminal neuralgia-induced anxiodepression via a hippocampus-to-prefrontal circuit.

Anxiety and depression are frequently observed in patients suffering from trigeminal neuralgia (TN), but neural circuits and mechanisms underlying this association are poorly understood. Here, we identified a dedicated neural circuit from the ventral hippocampus (vHPC) to the medial prefrontal cortex (mPFC) that mediates TN-related anxiodepression. We found that TN caused an increase in excitatory synaptic transmission from vHPCCaMK2A neurons to mPFC inhibitory neurons marked by the expression of corticotropin-releasing hormone (CRH). Activation of CRH+ neurons subsequently led to feed-forward inhibition of layer V pyramidal neurons in the mPFC via activation of the CRH receptor 1 (CRHR1). Inhibition of the vHPCCaMK2A-mPFCCRH circuit ameliorated TN-induced anxiodepression, whereas activating this pathway sufficiently produced anxiodepressive-like behaviors. Thus, our studies identified a neural pathway driving pain-related anxiodepression and a molecular target for treating pain-related psychiatric disorders.

Global prevalence of Plasmodium infection in wild birds: A systematic review and meta-analysis.

Avian malaria is a vector-borne parasitic disease caused by Plasmodium infection transmitted to birds by mosquitoes. The aim of this systematic review was to analyze the global prevalence of malaria and risk factors associated with infection in wild birds. A systematic search of the databases CNKI, WanFang, VIP, PubMed, and ScienceDirect was performed from database inception to 24 February 2023. The search identified 3181 retrieved articles, of which 52 articles met predetermined inclusion criteria. Meta-analysis was performed using the random-effects model. The estimated pooled global prevalence of Plasmodium infection in wild birds was 16%. Sub-group analysis showed that the highest prevalence was associated with adult birds, migrant birds, North America, tropical rainforest climate, birds captured by mist nets, detection of infection by microscopy, medium quality studies, and studies published after 2016. Our study highlights the need for more understanding of Plasmodium prevalence in wild birds and identifying risk factors associated with infection to inform future infection control measures.