Ultrasensitive In2O3-Based Nanoflakes for Lung Cancer Diagnosis and the Sensing Mechanism Investigated by Operando Spectroscopy.

Rapid gas sensing with high sensitivity and selectivity is pivotal in advanced production, in smart living, and increasingly in medical health applications. This study presents a novel Pt@InNiOx nanoflake isoprene sensor that achieves an exceptionally low limit of detection (LOD) at 2 ppb, the lowest reported for isoprene sensors to date. Notably, it exhibits high selectivity and remarkable antihumidity capacity, thus meeting the stringent requirements for lung cancer screening. To unravel the sensing mechanism, we fabricate an operando DRIFTS-Raman cell coupled to online electrical measurements. It reveals that the ultrasensitive performance of Pt@InNiOx nanoflakes stems from the activated conjugated structure of isoprene by Pt nanoclusters and from the enhanced isoprene adsorption and electron interaction due to the nanoflake morphology. The p-n junction constructed by doping Ni maintains Fermi level equilibrium, shielding it from humidity interference. Practically, we integrate these ultrasensitive Pt@InNiOx nanoflakes into a miniaturized portable electronic device that successfully distinguishes lung cancer patients with expiratory isoprene below 40 ppb, from the healthy population with isoprene above 60 ppb, enabling an accurate diagnosis in clinics. Our work not only provides a breakthrough in low-cost, noninvasive cancer screening through breath analysis but also advances the rational design of cutting-edge gas sensing materials.

Glioma-associated oncogene homolog 1 in breast invasive carcinoma: a comprehensive bioinformatic analysis and experimental validation.

Background: Breast cancer, despite significant advancements in treatment, remains a major cause of cancer-related deaths among women. Immunotherapy, an emerging therapeutic strategy, offers promise for better outcomes, particularly through the modulation of immune functions. Glioma-Associated Oncogene Homolog 1 (GLI1), a transcription factor implicated in cancer biology, has shown varying roles in different cancers. However, its immunoregulatory functions in breast invasive carcinoma (BRCA) remain elusive. The current study aimed to unravel the expression patterns and immune-regulatory roles of GLI1 in BRCA. Methods: Utilizing multiple bioinformatic platforms (TIMER2.0, GEPIA2, and R packages) based on The Cancer Genome Atlas (TCGA) and/or Genotype-Tissue Expression (GTEx) databases, we analyzed the expression of GLI1 in BRCA and its pan-cancer expression profiles. We further validated these findings by conducting qPCR and immunohistochemical staining on clinical BRCA samples. Kaplan-Meier analysis and Cox proportional hazards regression were performed to assess the prognostic value of GLI1. Additionally, the association between GLI1 expression and immune infiltration within the tumor immune microenvironment (TMIE) was examined. Results: The findings reveal dysregulated expression of GLI1 in numerous cancers, with a significant decrease observed in BRCA. High GLI1 expression indicated better survival outcomes and was correlated with the age and stage of BRCA patients. GLI1 was involved in immune status, as evidenced by its strong correlations with immune and stromal scores and the infiltration levels of multiple immune cells. Meanwhile, GLI1 was co-expressed with multiple immune-related genes, and high GLI1 expression was associated with the activation of immune-related pathways, such as binding to proteasome and mismatch repair and retinol metabolism signaling pathways. Additionally, the differential expression of GLI1 may be related to the effect of immunotherapy on CTLA-4, PD-1, and other signals, and can effectively predict the immune efficacy. Conclusion: Our study underscores the critical role of GLI1 in BRCA, both as a potential tumor suppressor and an immune regulator. The association between GLI1 expression and favorable prognosis suggests its potential as a prognostic biomarker and immunotherapeutic target in BRCA.

Mendelian randomization analysis of causal relationship between cheese intake and diabetic retinopathy.

AIM: To assess whether there is a possible causal link between the intake of cheese and the risk of diabetic retinopathy (DR) utilizing a two-sample Mendelian randomization (MR) analysis. METHODS: The research data were obtained from summary statistics of genome-wide association studies (GWAS). Genetic loci closely related to cheese intake were extracted as instrumental variables (IVs), and DR was the outcome variable. The data were extracted from individuals of European ethnicity. The data of cheese intake consisted of 451 486 samples with 9 851 867 single nucleotide polymorphisms (SNPs), while the DR data consisted of 206 234 samples with 16 380 446 SNPs. Sixty-one genetic loci closely related to cheese intake were selected as IVs. MR analysis was performed by inverse-variance weighted (IVW) method and MR-Egger regression respectively. The causal relationship between cheese intake and DR was evaluated using odds ratios (ORs) and 95% confidence intervals (CIs). Egger-intercept test was used to test horizontal pleiotropy and sensitivity analysis was performed by leave-one-out test. RESULTS: The P value of the IVW method was less than 0.05, indicating a significant negative correlation between cheese intake and DR. MR-Egger regression showed that the intercept was 0.01 with a standard error of 0.022, and a P-value of 0.634, indicating no evidence of horizontal pleiotropy affecting the IVs related to the exposure factors. Besides, heterogeneity tests confirmed the absence of heterogeneity, and the "leave-one-out" sensitivity analysis demonstrated that the results were stable. CONCLUSION: Cheese intake is causally negatively correlated with the occurrence of DR, and cheese intake could reduce the risk of DR.

Comprehensive detection and dissection of interlineage recombination events in the SARS-CoV-2 pandemic.

The global prevalence of the XBB lineage presents a formidable challenge posed by the recombinant SARS-CoV-2 virus. The understanding of SARS-CoV-2's recombination preference assumes utmost significance in predicting future recombinant variants and adequately preparing for subsequent pandemics. Thus, an urgent need arises to establish a comprehensive landscape concerning SARS-CoV-2 recombinants worldwide and elucidate their evolutionary mechanisms. However, the initial step, involving the detection of potential recombinants from a vast pool of over 10 million sequences, presents a significant obstacle. In this study, we present CovRecomb, a lightweight methodology specifically designed to effectively identify and dissect interlineage SARS-CoV-2 recombinants. Leveraging CovRecomb, we successfully detected 135,567 putative recombinants across the entirety of 14.5 million accessed SARS-CoV-2 genomes. These putative recombinants could be classified into 1451 distinct recombination events, of which 206 demonstrated transmission spanning multiple countries, continents, or globally. Hotspot regions were identified in six specific areas, with prominence observed in the latter halves of the N-terminal domain and receptor-binding domain within the spike (S) gene. Epidemiological investigations revealed extensive recombination events occurring among different SARS-CoV-2 (sub)lineages, independent of lineage prevalence frequencies.

Long-term transcranial ultrasound stimulation regulates neuroinflammation to ameliorate post-myocardial infarction cardiac arrhythmia and remodeling.

BACKGROUND: Sympathetic overactivation and neuroinflammation in the paraventricular nucleus (PVN) are crucial factors in post-myocardial infarction (MI) cardiac remodeling and ventricular arrhythmias (VAs). Prior study has indicated that low-intensity focused ultrasound stimulation could attenuate sympathetic neuroinflammation within the PVN to prevent the occurrence of VAs in an acute MI model. Meanwhile, the cGAS-STING pathway has shown potential to ameliorate the neuroinflammatory response. However, the effect and mechanisms of long-term transcranial ultrasound stimulation (LTUS) for modulating neuroinflammation in the chronic stage of MI remain unclear. OBJECTIVE: This study aimed to ascertain whether LTUS could mitigate post-MI neuroinflammation and improve cardiac arrhythmia and remodeling through the cGAS-STING pathway. METHODS: Thirty-six SD rats were equally randomized to the sham group (pseudo-MI modeling), chronic MI group (MI modeling), and LTUS group (MI modeling and long-term ultrasound stimulation). Transcranial ultrasound stimulation (15 min/d) was conducted on the PVN for 4 consecutive weeks. After 4-week intervention, echocardiography, electrophysiologic experiments, and histopathologic staining were performed to assess the role of LTUS on post-MI neuroinflammation and cardiac remodeling. RESULTS: The results indicated that LTUS significantly facilitated microglial M1 to M2 polarization through the cGAS-STING signaling pathway within the PVN. Furthermore, LTUS inhibited MI-induced sympathetic neuroinflammation, thereby improving cardiac dysfunction, ameliorating cardiac remodeling, and reducing VA inducibility. CONCLUSION: Long-term ultrasound stimulation of the PVN was found to alleviate post-MI neuroinflammation and to improve cardiac remodeling, which might inspire novel insights and clinical strategies for noninvasive neuromodulation and the treatment of post-MI VAs.

Comparative Transcriptome Analysis of Salt-Tolerant and -Sensitive Soybean Cultivars under Salt Stress.

Soil salinity is a major limiting factor in soybean (Glycine max (L.) Merr.) yield in Xinjiang, China. Therefore, breeding soybean to tolerate highly saline soils is crucial to improve its yield. To explore the molecular mechanisms underlying the response of soybean to salt stress, we performed a comparative transcriptome analysis of root and leaf samples collected from two local soybean cultivars. The salt-tolerant cultivar 'Xin No. 9' (X9) showed higher photosynthetic activity than the salt-sensitive cultivar 'Xinzhen No. 9' (Z9) under salt stress. In total, we identified 13,180 and 13,758 differential expression genes (DEGs) in X9 and Z9, respectively, of which the number of DEGs identified in roots was much higher than that in leaves. We constructed the co-expression gene modules and conducted Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The results suggested there were distinct differences in the mechanisms of response to salt stress between the two soybean cultivars; i.e., the salt-tolerant cultivar X9 exhibited alterations in fundamental metabolism, whereas the salt-sensitive cultivar Z9 responded to salt stress mainly through the cell cycle. The possible crosstalk among phytohormone signaling, MAPK signaling, phenylpropanoid biosynthesis, starch and sucrose metabolism, and ribosome metabolism may play crucial roles in the response to salt stress in soybean. Our results offered a comprehensive understanding of the genes and pathways involved in the response to salt stress in soybean and provided valuable molecular resources for future functional studies and the breeding of soybean varieties with enhanced tolerance to salinity.

Determination of indole-3-acetic acid using disposable molecularly imprinted electrochemical sensors based on bifunctional monomers.

Stainless steel sheets were coated with carbon ink to obtain disposable carbon electrodes, which were used as supports for moleculary imprinted polymer (MIP) electrochemical sensors by electropolymerizing o-phenylenediamine and o-aminophenol along with indole-3-acetic acid (IAA) as the template. After optimization, the MIP biosensors could be used for sensitive and selective detection of IAA with the limit of quantification of 0.1 µM. Our experimental results showed that stable and reproducible electrochemical responses could be achieved for the disposable MIP biosensors. This approach was successfully used for detection of IAA in different tissues of pea sprouts. This study reveals the potential of MIP electrochemical sensors in practical applications and shrinks the trench between the research and the real world.

Dissection of the cell communication interactions in lung adenocarcinoma identified a prognostic model with immunotherapy efficacy assessment and a potential therapeutic candidate gene ITGB1.

Background: The tumor microenvironment (TME) in lung adenocarcinoma (LUAD) influences tumor progression and immunosuppressive phenotypes through cell communication. We aimed to decipher cellular communication and molecular patterns in LUAD. Methods: We analyzed scRNA-seq data from LUAD patients in multiple cohorts, revealing complex cell communication networks within the TME. Using cell chat analysis and COSmap technology, we inferred LUAD's spatial organization. Employing the NMF algorithm and survival screening, we identified a cell communication interactions (CCIs) model and validated it across various datasets. Results: We uncovered intricate cell communication interactions within the TME, identifying three LUAD patient subtypes with distinct prognosis, clinical characteristics, mutation status, expression patterns, and immune infiltration. Our CCI model exhibited robust performance in prognosis and immunotherapy response prediction. Several potential therapeutic targets and agents for high CCI score patients with immunosuppressive profiles were identified. Machine learning algorithms pinpointed the novel candidate gene ITGB1 and validated its role in LUAD tumor phenotype in vitro. Conclusion: Our study elucidates molecular patterns and cell communication interactions in LUAD as effective biomarkers and predictors of immunotherapy response. Targeting cell communication interactions offers novel avenues for LUAD immunotherapy and prognostic evaluations, with ITGB1 emerging as a promising therapeutic target.

Relationship between weight-adjusted-waist index and all-cause and cardiovascular mortality in individuals with type 2 diabetes.

AIM: To investigate the relationship between the weight-adjusted-waist index (WWI) and all-cause mortality as well as cardiovascular mortality in individuals with type 2 diabetes. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 and the UK Biobank database. Restricted cubic spline curves and Cox proportional hazards models were employed to assess hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. RESULTS: In the UK Biobank database, compared with the lowest WWI quartile, the HR for all-cause and cardiovascular death in the highest quartile was 1.846 (95% CI 1.687-2.019) and 2.118 (95% CI 1.783-2.517), respectively, in the fully adjusted model. In the NHANES database, compared with the lowest WWI quartile, the highest quartile had an HR of 1.727 (95% CI 1.378-2.163) for all-cause death and 1.719 (95% CI 1.139-2.595) for cardiovascular death in the fully adjusted model. CONCLUSIONS: Our study indicates that WWI has a long-term synergistic negative impact on all-cause mortality and cardiovascular mortality in individuals with type 2 diabetes. The WWI is an independent predictor of mortality in individuals with type 2 diabetes.

HDAC2 promotes autophagy-associated HCC malignant progression by transcriptionally activating LAPTM4B.

Hepatocellular carcinoma (HCC) is a significant global health challenge. The activation of autophagy plays an essential role in promoting the proliferation and survival of cancer cells. However, the upstream regulatory network and mechanisms governing autophagy in HCC remain unclear. This study demonstrated that histone deacetylase 2 (HDAC2) regulates autophagy in HCC. Its expression was elevated in HCC tissues, and high HDAC2 expression was strongly associated with poor prognosis in individuals with HCC. Integrated in vitro and in vivo investigations confirmed that HDAC2 promotes autophagy and autophagy-related malignant progression in HCC. Mechanistically, HDAC2 bound specifically to the lysosome-associated protein transmembrane 4-ß (LAPTM4B) promoter at four distinct binding sites, enhancing its transcriptional activation and driving autophagy-related malignant progression in HCC. These findings establish LAPTM4B as a direct target gene of HDAC2. Furthermore, the selective inhibitor of HDAC2 effectively alleviated the malignant development of HCC. In addition, multivariate Cox regression analysis of 105 human HCC samples revealed that HDAC2 expression is an independent predictor of HCC prognosis. This study underscores the crucial role of the HDAC2-LAPTM4B axis in regulating autophagy in the malignant evolution of HCC and highlights the potential of targeting HDAC2 to prevent and halt the malignant progression of HCC.

YAP O-GlcNAcylation contributes to corneal epithelial cell ferroptosis under cigarette smoke exposure.

Cigarette smoke (CS) is an important indoor air pollutant associated with an increased risk of ocular surface disease. As the eye's outermost layer, the cornea is highly sensitive to air pollutants like CS. However, the specific mechanisms linking CS exposure to corneal dysfunction have not been fully elucidated. In the present study, we found that CS exposure damages corneal epithelial cells, accompanied by increased iron (Fe2+) levels and lipid peroxidation, both hallmarks of ferroptosis. Ferroptosis inhibitors, including Ferrostatin-1 (Fer-1) and Deferoxamine mesylate (DFO), protect against CS-induced cell damage. To understand the underlying mechanisms, we investigated how CS affects iron and lipid metabolism. Our results showed that CS could upregulate intracellular iron levels by increasing TFRC expression and promote lipid peroxidation by increasing ACSL4 expression. Silencing ACSL4 or TFRC expression prevented CS-induced ferroptosis. Furthermore, we found that the upregulation of TFRC and ACSL4 was driven by increased YAP transcription. Pharmacological or genetic inhibition of YAP effectively prevented corneal epithelial cell ferroptosis under CS stimulation. Additionally, our results suggest that CS exposure could increase O-GlcNAc transferase activity, leading to YAP O-GlcNAcylation. This glycosylation of YAP interfered with its K48-linked ubiquitination, resulting in YAP stabilization. Collectively, we found that CS exposure induces corneal epithelial cell ferroptosis via the YAP O-GlcNAcylation, and provide evidence that CS exposure is a strong risk factor for ocular surface disease.

Mitochondria-targeted sonodynamic modulation of neuroinflammation to protect against myocardial ischemia‒reperfusion injury.

Sympathetic hyperactivation and inflammatory responses are the main causes of myocardial ischemia‒reperfusion (I/R) injury and myocardial I/R-related ventricular arrhythmias (VAs). Previous studies have demonstrated that light-emitting diodes (LEDs) could modulate post-I/R neuroinflammation, thus providing protection against myocardial I/R injury. Nevertheless, further applications of LEDs are constrained due to the low penetration depth (<1 cm) and potential phototoxicity. Low-intensity focused ultrasound (LIFU), an emerging noninvasive neuromodulation strategy with deeper penetration depth (∼10 cm), has been confirmed to modulate sympathetic nerve activity and inflammatory responses. Sonodynamic therapy (SDT), which combines LIFU with sonosensitizers, confers additional advantages, including superior therapeutic efficacy, precise localization of neuronal modulation and negligible side effects. Herein, LIFU and SDT were introduced to modulate post-myocardial I/R neuroinflammation to protect against myocardial I/R injury. The results indicated that LIFU and SDT inhibited sympathetic neural activity, suppressed the activation of astrocytes and microglia, and promoted microglial polarization towards the M2 phenotype, thereby attenuating myocardial I/R injury and preventing I/R-related malignant VAs. These insights suggest that LIFU and SDT inspire a noninvasive and efficient neuroinflammatory modulation strategy with great clinical translation potential thus benefiting more patients with myocardial I/R in the future. STATEMENT OF SIGNIFICANCE: Myocardial ischemia-reperfusion (I/R) may cause I/R injury and I/R-induced ventricular arrhythmias. Sympathetic hyperactivation and inflammatory response play an adverse effect in myocardial I/R injury. Previous studies have shown that light emitting diode (LED) can regulate I/R-induced neuroinflammation, thus playing a myocardial protective role. However, due to the low penetration depth and potential phototoxicity of LED, it is difficult to achieve clinical translation. Herein, we introduced sonodynamic modulation of neuroinflammation to protect against myocardial I/R injury, based on mitochondria-targeted nanosonosensitizers (CCNU980 NPs). We demonstrated that sonodynamic modulation could promote microglial autophagy, thereby preventing myocardial I/R injury and I/R-induced ventricular arrhythmias. This is the first example of sonodynamic modulation of myocardial I/R-induced neuroinflammation, providing a novel strategy for clinical translation.

Association between all-cause mortality and vascular complications in U.S. adults with newly diagnosed type 2 diabetes (NHANES 1999-2018).

AIMS: The impact of macrovascular and microvascular complications, the common vascular complications of type 2 diabetes, on long-term mortality has been well evaluated, but the impact of different complications of newly diagnosed type 2 diabetes (diagnosed within the past 2 years) on long-term mortality has not been reported. We aimed to investigate the relationship between all-cause mortality and vascular complications in U.S. adults (aged ≥ 20 years) with newly diagnosed type 2 diabetes. METHODS: We used data from the 1999-2018 National Health and Nutritional Examination Surveys (NHANES). Cox proportional hazard models was used to assess hazard ratios (HR) and 95% confidence intervals for all-cause mortality. RESULTS: A total of 928 participants were enrolled in this study. At a mean follow-up of 10.8 years, 181 individuals died. In the fully adjusted model, the hazard ratio (HR) (95% confidence interval [CI]) of all-cause mortality for individuals with any single complication compared with those with newly diagnosed type 2 diabetes without complications was 2.24 (1.37, 3.69), and for individuals with two or more complications was 5.34 (3.01, 9.46).Co-existing Chronic kidney disease (CKD) and diabetic retinopathy (DR) at baseline were associated with the highest risk of death (HR 6.07[2.92-12.62]), followed by CKD and cardiovascular disease (CVD) (HR 4.98[2.79-8.89]) and CVD and DR (HR 4.58 [1.98-10.57]). CONCLUSION: The presence of single and combined diabetes complications exerts a long-term synergistic adverse impact on overall mortality in newly diagnosed U.S. adults with type 2 diabetes, underscoring the importance of comprehensive complication screening to enhance risk stratification and treatment.

Tailoring Polyamide Nanofiltration Membranes by Switching Charge of Nanocellulose Interlayers.

The interlayer strategy has emerged as an effective approach for modulating the interfacial polymerization process and improving the permeability and selectivity of polyamide membranes. However, the underlying mechanisms by which charged interlayers influence the interfacial polymerization process remain inadequately understood. In this study, we utilized two distinct charged cellulose nanofibers, namely, carboxylated cellulose (⊖-CNF) and quaternized cellulose ([Formula: see text]-CNF), as interlayers to regulate the interfacial polymerization process. Through simulation results, isothermal titration calorimetry (ITC) and UV tests, we demonstrated that the [Formula: see text]-CNF interlayer, which possesses stronger hydration capability and better piperazine affinity, enhanced the diffusion of piperazine across the reaction interface compared with the ⊖-CNF interlayer. This led to an acceleration of the interfacial polymerization process and the formation of a denser membrane structure. Further investigation revealed that the charged interlayers significantly influenced the surface charging properties of the resulting nanofiltration membranes within a 30 nm range of electrostatic effects. Specifically, the ⊖-CNF interlayer conferred a higher negative charge to the membrane surface, while the [Formula: see text]-CNF interlayer endowed the membranes with a lower surface negative charge. Leveraging these differences, the ⊖-i-TFC membranes exhibited exceptional separation performance for divalent anions, achieving a SO42-/Cl- selectivity of 136. Conversely, the [Formula: see text]-i-TFC membrane demonstrated an enhanced separation of divalent cations, displaying a Mg2+/Na+ selectivity of 3.5. This study lays the groundwork for regulating the surface charging properties of polyamide membranes, offering potential advancements in nanofiltration applications.

Relationship between the Cell Death-Inducing DNA Fragmentation Factor 45-Like Effector Protein Family and the Risk of Dyslipidemia.

According to the research, obesity is associated with hyperlipidemia, hypertension, and type 2 diabetes mellitus, which are grouped as metabolic syndrome. Notably, under the obese status, the adipocyte could accumulate excessive lipid as lipid droplets (LDs), leading the dysfunctional fat mass. Recently, emerging evidence has shown that the cell death-inducing DNA fragmentation factor 45-like effector protein (CIDE) family played an important role in regulating lipid metabolism. In addition, diverse CIDE proteins were also confirmed to influence the intracellular lipid metabolism, such as within adipocyte, hepatocyte, and macrophage. Nevertheless, the results which showed the regulatory influence of CIDE proteins are significantly contradictory from in vitro experiments and in vivo clinical studies. Similarly, recent studies have changed the perception of these proteins, redefining them as regulators of lipid droplet dynamics and fat metabolism, which contribute to a healthy metabolic phenotype in humans. However, the underlying mechanisms by which the diverse CIDE proteins alter lipid metabolism are not elucidated. In the current review, the understandings of CIDE proteins in lipid catabolism were well-summarized. On the other hand, the relatively mechanisms were also proposed for the further understandings of the CIDE protein family.

HDL regulates the risk of cardiometabolic and inflammatory-related diseases: Focusing on cholesterol efflux capacity.

Dyslipidemia, characterized by higher serum concentrations of low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglyceride (TG), and lower serum concentrations of high-density lipoprotein cholesterol (HDL-C), is confirmed as a hallmark of cardiovascular diseases (CVD), posing serious risks to the future health of humans. Aside from the role of HDL-C concentrations, the capacity of cholesterol efflux to HDL is being identified as an enssential messurement for the dyslipidemic morbidity. Through inducing the progression of reverse cholesterol transport (RCT), the HDL-related cholesterol efflux plays a vital role in atherosclerotic plaque formation. In addition, increasing results demonstrated that the relationships between cholesterol efflux and cardiovascular events might be influenced by multiple factors, such as atherosclerosis, diabetes, and, inflammatory diseases. These risk factors could affect the intracellular composition of HDL, which might subsqently influence the cholesterol efflux process induced by HDL particle. In the present comprehensive article, we summarize the latest findings which described the modulatory roles of HDL in cardiometabolic disorders and inflammatory related diseases, focusing on its capacity in mediating cholesterol efflux. Moreover, the potential mechanisms whereby HDL regulate the risk of cardiometabolic disorders or inflammatory related diseases, at least partly, via cholesterol efflux pathway, are also well-listed.

PFKFB3 Regulates the Growth and Migration of Ovarian Cancer Cells through Pyroptosis and Warburg Effect Progression.

Ovarian cancer is one of the most common malignant tumors in female reproductive organs. Its incidence rate is second only to uterine body cancer and cervical cancer, posing a serious threat to women's health. Herein, we explored that PFKFB3 in cancer progression of ovarian cancer and its underlying mechanism. All the serum samples from ovarian cancer were collected by our hospital. PFKFB3 mRNA expressions in patients with ovarian cancer and ovarian cancer cell lines were up-regulated. PFKFB3 protein expressions in ovarian cancer cells were induced. ovarian cancer patients with high PFKFB3expression had lower survival rate. The PFKFB3gene promoted cell proliferation and EDU cells, and increased cell metastasis of ovarian cancer. Si-PFKFB3 reduced cell proliferation and EDU cells, and decreased cell metastasis of ovarian cancer. PFKFB3 gene up-regulation reduced caspase-3/9 activity levels of ovarian cancer. Si-PFKFB3 also promoted caspase-3/9 activity levels of ovarian cancer. PFKFB3 gene promoted Warburg effect progression of ovarian cancer. PFKFB3 gene reduced NLRP3-induced pyroptosis of ovarian cancer. PFKFB3 suppressed NLRP3 expression. NLRP3 was one target spot for PFKFB3 on pyroptosis of ovarian cancer. Taken together, we conclude that PFKFB3 suppressed NLRP3 axis to reduce pyroptosis and increase Warburg effect progression of ovarian cancer, and provide molecular insight into the mechanisms by which the PFKFB3 regulates pyroptosis of ovarian cancer.

Gut microbiota diversity in a dung beetle (Catharsius molossus) across geographical variations and brood ball-mediated microbial transmission.

The dung beetle primarily feeds on the feces of herbivorous animals and play a crucial role in ecological processes like material cycles and soil improvement. This study aims to explore the diversity and composition of the gut microbiota of Catharsius molossus (a renowned dung beetle originating from China and introduced to multiple countries for its ecological value) and exploring whether these gut microbes are transmitted vertically across generations. Using 16S rRNA and ITS rRNA gene sequencing techniques, we described the diversity and composition of gut microbes in C. molossus from different localities and different developmental stages (Egg, young larvae and old larvae). We discovered that the diversity of gut microbiota of dung beetles varied obviously among different geographical localities and different developmental stages, and we also discussed the potential influencing factors. Interestingly, the microbial community structure within the brood balls is more similar to male dung beetle than to that of females, which is consistent with the observation that the brood ball is constructed by the male dung beetle, with the female laying egg in it at the final step. This unique breeding method facilitates offspring in inheriting microbial communities from both the mother and the father. Initially, the larvae's gut microbiota closely mirrors that of the parental gift in these brood balls. As larvae grow, significant changes occur in their gut microbiota, including an increase in symbiotic bacteria like Lactococcus and Enterococcus. Analysis of the gut bacteria of adult dung beetles across various localities and different developmental stages identified nine core genera in adults, contributing to 67.80% of the total microbial abundance, and 11 core genera in beetles at different developmental stages, accounting for 49.13% of the total. Notably, seven genera were common between these two core groups. Our results suggest that Parental gifts can play a role in the vertical transmission of microbes, and the abundance of probiotics increases with larval development, supporting the hypothesis that "larval feeding behavior occurs in two stages: larvae first feed on parental gifts to acquire necessary microbes, then enrich symbiotic microbiota through consuming their own feces."

Surgical management of a foramen magnum tumor via a far-lateral approach using an oblique straight incision: a case series report and technique note.

Objective: To review our single-institution experience in the surgical management of foramen magnum tumors via a far-lateral approach using an oblique straight incision. Methods: From October 2023 to January 2024, four cases of tumors in the foramen magnum area treated at the Capital Medical University-affiliated XuanWu hospital neurosurgery department were involved in this study. All cases were managed with a far-lateral approach using an oblique straight incision. We retrospectively reviewed the clinical and imaging data, as well as the surgical strategies employed. Results: Three cases of foramen magnum meningiomas and one case of glioma of the ventral medulla. All cases underwent a far-lateral approach using an oblique straight incision; all cases had a gross total resection, and the wounds healed well without cerebral fluid leakage or scalp hydrops. Except for one case of right foramen magnum meningioma, which had dysphagia and pneumothorax, the other cases were without any postoperative complications. Conclusion: A far-lateral approach using an oblique straight incision can preserve muscle integrity and minimize subcutaneous exposure, allowing for complete anatomical reduction of muscles. This craniectomy method is simple and replicable, making it worthy of further clinical practice.

The association between HLA-B variants and amoxicillin-induced severe cutaneous adverse reactions in Chinese han population.

Background: Amoxicillin (AMX) is among the most prescribed and the best tolerated antimicrobials worldwide. However, it can occasionally trigger severe cutaneous adverse reactions (SCAR) with a significant morbidity and mortality. The genetic factors that may be relevant to AMX-induced SCAR (AMX-SCAR) remain unclear. Identification of the genetic risk factor may prevent patients from the risk of AMX exposure and resume therapy with other falsely implicated drugs. Methodology: Four patients with AMX-SCAR, 1,000 population control and 100 AMX-tolerant individuals were enrolled in this study. Both exome-wide and HLA-based association studies were conducted. Molecular docking analysis was employed to simulate the interactions between AMX and risk HLA proteins. Results: Compared with AMX-tolerant controls, a significant association of HLA-B*15:01 with AMX-SCAR was validated [odds ratio (OR) = 22.9, 95% confidence interval (CI): 1.68-1275.67; p = 7.34 × 10-3]. Moreover, 75% carriers of HLA-B*15:01 in four patients with AMX-SCAR, and the carrier frequency of 10.7% in 1,000 control individuals and 11.0% in 100 AMX-tolerant controls, respectively. Within HLA-B protein, the S140 present in all cases and demonstrated the strongest association with AMX-SCAR [OR = 53.5, p = 5.18 × 10-4]. Molecular docking results also confirmed the interaction between AMX and S140 of the HLA-B protein, thus eliminating the false-positive results during in association analysis. Conclusion: Our findings suggest that genetic susceptibility may be involved in the development of AMX-SCAR in Han Chinese. However, whether the HLA-B variants observed in this study can be used as an effective genetic marker of AMX-induced SCAR still needs to be further explored in larger cohort studies and other ethnic populations.