The Value of Neutrophil-to-Lymphocyte Ratio in Predicting Mortality After Transjugular Intrahepatic Portosystemic Shunt Placement.

Background and Aims: The objective of this study was to investigate the effect of neutrophil-to-lymphocyte ratio (NLR) on the survival of cirrhotic patients with esophagogastric variceal bleeding (EGVB) treated with transjugular intrahepatic portosystemic shunt (TIPS). Methods: A total of 293 patients treated with TIPS were included. The receiver operator characteristic curve (ROC) was used to calculate the optimal cut-off values of parameters such as NLR. The Kaplan-Meier curve and Cox proportional risk model were used to evaluate the effects of NLR and other variables on 2-year all-cause mortality. Results: The area under the ROC for NLR was 0.634, with an optimal cutoff value of 4.9. Two-year mortality rates for patients with high (≥4.9) and low (<4.9) NLR were 22.1% and 9.3%, respectively (Log rank test: P = 0.002). After correcting for confounders, multivariate analysis demonstrated that NLR ≥ 4.9 (HR = 2.741, 95% CI 1.467-5.121, P = 0.002), age ≥ 63 (HR = 3.403, 95% CI 1.835-6.310, P < 0.001), and gender (male) (HR = 2.842, 95% CI 1.366-5.912, P = 0.001) were independent risk factors for the mortality outcome. Considering the stratification of early and selective TIPS treatment, high NLR still significantly increased the risk of mortality for patients (Log rank test: P = 0.007, HR = 2.317, 95% CI 1.232-4.356). Conclusion: NLR can help to predict survival in EGVB patients after TIPS, and the type of TIPS should also be considered in practical applications.

[Comparison of the efficacy of phlebotomy under touch pain point and ultrasound-guided puncture decompression in the treatment of acute calcific supraspinatus tendinitis].

OBJECTIVE: To compare the efficacy of blood letting under pain point touch and ultrasound-guided puncture decompression in the treatment of acute supraspinatus muscle calcifying tendinitis. METHODS: From January 2020 to January 2023, 45 patients with acute supraspinatus muscle calcifying tendinitis were selected and divided into treatment group and control group. In the treatment group, a total of 22 patients were treated with ultrasound-guided puncture decompression, including 16 females and 6 males, aged from 20 to 64 years old(39.31±5.80) years old, 11 on the left shoulder and 11 on the right shoulder. In the control group, there were 23 cases, including 15 females and 8 males, aged from 19 to 66 years old (40.67±6.13) years old, 12 on the left shoulder and 13 on the right shoulder. The treatment was treated with pain point touch bloodletting therapy. The visual analog scale (VAS) pain score, University of California, Los Angeles(UCLA) shoulder system score and shoulder Constant-Murley score were used to evaluate the therapeutic effect before treatment, 1 weeks, 1 month and 3 months after treatment, respectively. RESULTS: One patient in the control group gave up follow-up for personal reasons after 1 week of treatment, and the other 44 patients completed all follow-up. Six months after treatment, there were no recurrence cases in both groups. After statistical analysis, VAS pain score, UCLA score and Constant-Murley score of the treatment group and the control group were significantly different from those before treatment (P<0.05), and the improvement was more obvious in the treatment group. There was no statistical significance between the two groups (P>0.05). CONCLUSION: Bloodletting under pain point touch and ultrasound-guided puncture decompression are effective in the treatment of acute calcific supraspinatus tendinitis, with simple operation and low cost, which can effectively reduce local pain and effectively improve shoulder joint function. Primary hospitals can selectively operate treatment according to their own conditions.

The mediating role of family functioning between childhood trauma and depression severity in major depressive disorder and bipolar disorder.

BACKGROUND: Childhood trauma (CT) and family functioning exert significant influences on the course and long-term outcome of major depressive disorder (MDD) and bipolar disorder (BD) patients. Hence, we examined the intricate relationship between CT, family function, and the severity of depressive episodes in MDD and BD patients. METHODS: 562 patients with depressive episodes (336 MDD and 226 BD) and 204 healthy controls (HCs) were included in this retrospective study. The 17-item Hamilton Depression Rating Scale (HAMD-17), Childhood Trauma Questionnaire (CTQ), and Family Adaptability and Cohesion Evaluation Scale (FACES II-CV) were assessed. Pearson correlation analysis and mediation analysis were performed. RESULTS: CT had both a direct and indirect impact on depression severity in MDD and BD groups. In MDD, family adaptability mediated the impact of all CT subtypes on depression severity (Effect = 0.113, [0.030, 0.208]). In BD, family cohesion played a mediating role between emotional neglect (EN) and HAMD scores (Effect = 0.169, [0.008, 0.344]). Notable differences were observed in onset age, illness duration, episode frequency, family history, and CT subtypes between MDD and BD (P < 0.05). LIMITATIONS: This study has several limitations including recall bias, lack of objective family functioning measures, small sample size, and cross-sectional design. CONCLUSIONS: Family functioning mediated the impact of CT on depressive symptoms severity in MDD and BD patients. MDD patients with a history of CT exhibited reduced family adaptability, while BD patients with a history of EN had weaker familial emotional bonds. Our findings highlighted the importance of family-focused preventive interventions in mitigating the long-term effects of CT.

Electrophysiological predictors of early response to antidepressants in major depressive disorder.

BACKGROUND: Psychomotor retardation (PMR) is a core feature of major depressive disorder (MDD), which is characterized by abnormalities in motor control and cognitive processes. PMR in MDD can predict a poor antidepressant response, suggesting that PMR may serve as a marker of the antidepressant response. However, the neuropathological relationship between treatment outcomes and PMR remains uncertain. Thus, this study examined electrophysiological biomarkers associated with poor antidepressant response in MDD. METHODS: A total of 142 subjects were enrolled in this study, including 49 healthy controls (HCs) and 93 MDD patients. All participants performed a simple right-hand visuomotor task during magnetoencephalography (MEG) scanning. Patients who exhibited at least a 50 % reduction in disorder severity at the endpoint (>2 weeks) were considered to be responders. Motor-related beta desynchronization (MRBD) and inter- and intra-hemispheric functional connectivity were measured in the bilateral motor network. RESULTS: An increased MRBD and decreased inter- and intra-hemispheric functional connectivity in the motor network during movement were observed in non-responders, relative to responders and HCs. This dysregulation predicted the potential antidepressant response. CONCLUSION: Abnormal local activity and functional connectivity in the motor network indicate poor psychomotor function, which might cause insensitivity to antidepressant treatment. This could be regarded as a potential neural mechanism for the prediction of a patient's treatment response.

The immunological landscape and silico analysis of key paraptosis regulator LPAR1 in gastric cancer patients.

This study aims to identify key regulators of paraptosis in gastric cancer (GC) and explore their potential in guiding therapeutic strategies, especially in stomach adenocarcinoma (STAD). Genes associated with paraptosis were identified from the references and subjected to Cox regression analysis in the TCGA-STAD cohort. Using machine learning models, LPAR1 consistently ranked highest in feature importance. Multiple sequencing data showed that LPAR1 was significantly overexpressed in cancer-associated fibroblasts (CAFs). LPAR1 expression was significantly higher in normal tissues, and ROC analysis demonstrated its discriminative ability. Copy number alterations and microsatellite instability were significantly associated with LPAR1 expression. High LPAR1 expression correlated with advanced tumor grades and specific cancer immune subtypes, and multivariate analysis confirmed LPAR1 as an independent predictor of poor prognosis. LPAR1 expression was associated with different immune response metrics, including immune effector activation and upregulated chemokine secretion. High LPAR1 expression also correlated with increased sensitivity to compounds, such as BET bromodomain inhibitors I-BET151 and RITA, suggesting LPAR1 as a biomarker for predicting drug activity. FOXP2 showed a strong positive correlation with LPAR1 transcriptional regulation, while increased methylation of LPAR1 promoter regions was negatively correlated with gene expression. Knockdown of LPAR1 affected cell growth in most tumor cell lines, and in vitro experiments demonstrated that LPAR1 influenced extracellular matrix (ECM) contraction and cell viability in the paraptosis of CAFs. These findings suggest that LPAR1 is a critical regulator of paraptosis in GC and a potential biomarker for drug sensitivity and immunotherapy response. This underscores the role of CAFs in mediating tumorigenic effects and suggests that targeting LPAR1 could be a promising strategy for precision medicine in GC.

Evaluating coronary arteries and predicting MACEs using CCTA in lung cancer patients receiving chemotherapy or chemoradiotherapy.

BACKGROUND: Whether coronary computed-tomography angiography (CCTA) can detect cancer treatment-related impairments of coronary artery and predict major adverse cardiovascular events (MACEs) in lung cancer patients receiving chemotherapy (CHT) or chemoradiotherapy (CRT) is unclear. OBJECTIVES: This study aimed to evaluate coronary arteries using CCTA parameters and explore the association of these parameters with MACEs in patients with lung cancer receiving CHT or CRT. MATERIALS AND METHODS: This study retrospectively collected data from 697 lung cancer patients who received CHT or CRT and underwent CCTA examination within 2 weeks before or after treatment from June 2013 to May 2019. The patients were divided into CHT and CRT group, and for the control group, the propensity score matching (PSM) was used and 125 participants without carcinoma with a single CCTA examination were included. CCTA parameters, assessed using artificial intelligence software, were compared across different groups (control vs. CHT & CRT; CHT vs. CRT). We analyzed associations between CCTA parameters and MACEs using a Cox-regression model and Kaplan-Meier curves to compare MACE-free survival rates. RESULTS: Before CHT or CRT, compared with the control group, in CHT&CRT group we observed higher fat attenuation index (FAI), coronary-artery calcium (CAC) score, CAD-RADS classification, stenosis severity and lower computed-tomography fractional flow reserve (CT-FFR; all P<0.05). After treatment, the CT-FFR decreased and the FAI increased; simultaneously, we observed a lower CT-FFR and higher FAI (all P<0.05) in the CRT than in the CHT group. Among the 146 cases developed MACEs, lower CT-FFR and higher FAI values were found compared with the non-MACE group (all P<0.05), and CT-FFR and FAI before treatment were associated with MACEs. CONCLUSION: Cancer treatment-related impairments of coronary arteries could be identified using CT-FFR and FAI. Before treatment, these parameters were associated with MACEs in lung cancer patients receiving CHT or CRT.

Identification of prognostic biomarkers for hepatocellular carcinoma with vascular invasion.

OBJECTIVE: Vascular invasion (VI) profoundly impacts the prognosis of hepatocellular carcinoma (HCC), yet the underlying biomarkers and mechanisms remain elusive. This study aimed to identify prognostic biomarkers for HCC patients with VI. METHODS: Transcriptome data from primary HCC tissues and HCC tissues with VI were obtained through the Genome Expression Omnibus database. Differentially expressed genes (DEGs) in the two types of tissues were analyzed using functional enrichment analysis to evaluate their biological functions. We examined the correlation between DEGs and prognosis by combining HCC transcriptome data and clinical information from The Cancer Genome Atlas database. Univariate and multivariate Cox regression analyses, along with the least absolute shrinkage and selection operator (LASSO) method were utilized to develop a prognostic model. The effectiveness of the model was assessed through time-dependent receiver operating characteristic (ROC) curve, calibration diagram, and decision curve analysis. RESULTS: In the GSE20017 and GSE5093 datasets, a total of 83 DEGs were identified. Gene Ontology analysis indicated that these DEGs were predominantly associated with xenobiotic stimulus, collagen-containing extracellular matrix, and oxygen binding. Additionally, Kyoto Encyclopedia of Genes and Genomes analysis revealed that the DEGs were primarily involved in immune defense and cellular signal transduction. Cox and LASSO regression further identified 7 genes (HSPA8, ABCF2, EAF1, MARCO, EPS8L3, PLA3G1B, C6), which were used to construct a predictive model in the training cohort. We used X-tile software to calculate the optimal cut-off value to stratify HCC patients into low-risk and high-risk groups. Notably, the high-risk group exhibited poorer prognosis than the low-risk group (P < 0.001). The model demonstrated area under the ROC curve (AUC) values of 0.815, 0.730, and 0.710 at 1-year, 3-year, and 5-year intervals in the training cohort, respectively. In the validation cohort, the corresponding AUC values were 0.701, 0.571, and 0.575, respectively. The C-index of the calibration curve for the training and validation cohorts were 0.716 and 0.665. Decision curve analysis revealed the model's efficacy in guiding clinical decision-making. CONCLUSIONS: The study indicates that 7 genes may be potential prognostic biomarkers and treatment targets for HCC patients with VI.

Targeting OGF/OGFR signal to mitigate doxorubicin-induced cardiotoxicity.

Enkephalins are reportedly correlated with heart function. However, their regulation in the heart remains unexplored. This study revealed a substantial increase in circulating levels of opioid growth factor (OGF) (also known as methionine enkephalin) and myocardial expression levels of both OGF and its receptor (OGFR) in subjects treated with doxorubicin (Dox). Silencing OGFR through gene knockout or using adeno-associated virus serotype 9 carrying small hairpin RNA effectively alleviated Dox-induced cardiotoxicity (DIC) in mice. Conversely, OGF supplementation exacerbated DIC manifestations, which could be abolished by administration of the OGFR antagonist naltrexone (NTX). Mechanistically, the previously characterized OGF/OGFR/P21 axis was identified to facilitate DIC-related cardiomyocyte apoptosis. Additionally, OGFR was observed to dissociate STAT1 from the promoters of ferritin genes (FTH and FTL), thereby repressing their transcription and exacerbating DIC-related cardiomyocyte ferroptosis. To circumvent the compromised therapeutic effects of Dox on tumors owing to OGFR blockade, SiO2-based modifiable lipid nanoparticles were developed for heart-targeted delivery of NTX. The pretreatment of tumor-bearing mice with the assembled NTX nanodrug successfully provided cardioprotection against Dox toxicity without affecting Dox therapy in tumors. Taken together, this study provides a novel understanding of Dox cardiotoxicity and sheds light on the development of cardioprotectants for patients with tumors receiving Dox treatment.

Effects of degreasing pretreatment on immunohistochemistry and molecular analysis of gastrointestinal and breast cancer samples.

Lymph node status is a key factor in determining stage, treatment, and prognosis in cancers. Small lymph nodes in the fat-rich gastrointestinal and breast cancer specimens are easily missed in conventional sampling methods. This study examined the effectiveness of degreasing pretreatment with dimethyl sulfoxide (DMSO) in lymph node detection and its impact on the analysis of clinical treatment-related proteins and molecules. Thirty-three cases of gastrointestinal cancer specimens from radical gastrectomy and 63 cases of breast cancer specimens from modified radical mastectomy were included. After routine sampling of lymph nodes, the specimens were immersed in DMSO for 30 minutes for defatting. We assessed changes in the number of detected lymph nodes and pN staging in 33 gastrointestinal cancer specimens and 37 breast cancer specimens. Additionally, we analyzed histological characteristics, Masson's trichrome special staining, and immunohistochemistry (gastrointestinal cancer: MMR, HER2, PD-L1; breast cancer: ER, PR, AR, HER2, Ki-67, PD-L1). Molecular status was evaluated for colorectal cancer (KRAS, NRAS, BRAF, MSI) and breast cancer (HER2) in gastrointestinal cancer specimens and the remaining 26 breast cancer specimens. Compared to conventional sampling, DMSO pretreatment increased the detection rate of small lymph nodes (gastrointestinal cancer: p<0.001; breast cancer: p<0.001) and improved pN staging in one case each of gastric cancer, colon cancer, and rectal cancer (3/33, 9.1%). No significant difference in the morphology, special staining, protein, and molecular status of cancer tissue after DMSO treatment were found. Based on these results and our institutional experience, we recommend incorporating DMSO degreasing pretreatment into clinical pathological sampling practices.

Roxarsone reduces earthworm-mediated nutrient cycling by suppressing aggregate formation and enzymic activity in soil with manure application.

The application of manure and earthworms are frequently used in fertilization practices to improve C, N, and P cycling in soil, which may be adversely affected by roxarsone (ROX), as an organoarsenical pollutant. To effectively address this issue, in this work, the interactive impacts of ROX and earthworm Eisenia foetida on the aggregate formation, input of organic carbon (OC), and changes in the available N and P following 56-day cultivation were systematically investigated. Compared to the control, earthworms increased the mean weight diameter (MWD) of the soil aggregates from 0.6 to 1.1 mm. Thereby, they activated soil enzymes including catalase (CAT), sucrase (SC), urease (UE), and neutral phosphatase (NP), with the soil's pH decreased to 7.1. Consequently, the values of OC, soluble nitrite (NO3-N), and Olsen-P content were respectively increased by 0.78-, 1.69-, and 0.87- folds in the E treatment (14.3 vs. 25.5 g/kg, 12.8 vs. 33.3 mg/kg, and 7.8 vs. 14.6 mg/kg). Although the changes in the R treatment were slight, ROX reduced the earthworm-mediated improvements of soil fertility during the application of the RE treatment compared to the E treatment, i.e., the values of MWD, OC, NO3-N, and Olsen-P were reduced to 0.9 mm, 20.4 g/kg, 25.4 mg/kg, and 11.6 mg/kg, respectively. From the well-fitted structural equation models, it was demonstrated that earthworms enhanced the aggregate formation and nutrient cycling of OC, NO3-N, and Olsen-P, which were inhibited by ROX. Overall, these adverse effects can be offset by earthworm addition, which can play the dual role of monitor and driver for the soil properties. Our work provides insightful strategies for ROX-bearing manure management.

Heterologous activation and metabolites identification of the pks7 gene cluster from Saccharopolyspora erythraea.

The microbial genome remains a huge treasure trove for the discovery of diverse natural products. Saccharopolyspora erythraea NRRL23338, the industry producer of erythromycin, has a dozen of biosynthetic gene clusters whose encoding products are unidentified. Heterologous expression of one of the polyketide clusters pks7 in Streptomyces albus B4 chassis resulted in the characterization of its function responsible for synthesizing both 6-methylsalicyclic acid and 6-ethylsalicyclic acid. Meanwhile, two new 6-ethylsalicyclic acid ester derivatives were isolated as shunt metabolites. Their structures were identified by comprehensive analysis of MS and NMR experiments. Putative functions of genes within the pks7 BGC were also discussed.

Phytotoxic responses of acrocarpous moss Campylopus schmidii as bioindicators in copper and cadmium contaminated environments: A comprehensive assessment.

Mosses play a vital role in environmental research as reliable biomonitoring tools. This study aims to understand the accumulation and distribution patterns of Cu and Cd in the acrocarpous moss [Campylopus schmidii (Müll. Hal.) A. Jaeger] (C.schmidii). In controlled in vitro experiments, C.schmidii cultures were exposed to varying concentrations of copper (Cu) and cadmium (Cd) stress (0, 10, 25, 50 µmol/L) in aquatic media. The study systematically evaluated the moss's response, including observing appearance features, oxidative traits, and accumulation characteristics. Scanning electron microscopy with energy-dispersive X-ray spectroscopy analyses were employed. They aimed to characterize and determine the distribution of metal particles in different parts of the mosses under high concentration treatments (50 µmol/L Cd, 50 µmol/L Cu, 50 µmol/L Cu and Cd). Results indicated that C.schmidii exhibited greater tolerance to Cu compared to Cd, as evidenced by significantly higher soluble protein content and lipid peroxidation with increasing concentrations. However, Cd stress induced severe damage, including widespread chlorosis, reduced chlorophyll content, and surface fragmentation. Both Cu and Cd were found to stimulate antioxidant levels by increasing the activity of hydrogen peroxide and peroxidase, thus reducing the accumulation of free radicals in C.schmidii. Additionally, the results revealed differential metal distribution. Higher Cu (2.23%) and lower Cd (0.54%) accumulation were observed at the bottom of gametophores, with Cd content 180.46% higher than Cu at the top. This study provides valuable insights into the potential application of acrocarpous mosses for biomonitoring and phytoremediation. It suggests specific strategies for metal deposition and absorption, such as utilizing upper, younger parts for Cd absorption and lower parts for Cu remediation in soil.

Targeting HTR2B suppresses non-functioning pituitary adenoma growth and sensitizes cabergoline treatment via inhibiting Gαq/PLC/PKCγ/STAT3 axis.

BACKGROUND: Managing non-functioning pituitary adenomas (NFPAs) is difficult due to limited drug treatments. Cabergoline's (CAB) effectiveness for NFPAs is debated. This study explores the role of HTR2B in NFPAs and its therapeutic potential. METHODS: We conducted screening of bulk RNA-sequencing data to analyze HTR2B expression levels in NFPA samples. In vitro and in vivo experiments were performed to evaluate the effects of HTR2B modulation on tumor growth and cell cycle regulation. Mechanistic insights into the HTR2B-mediated signaling pathway were elucidated using pharmacological inhibitors and molecular interaction assays. RESULTS: Elevated HTR2B expression was detected in NFPA samples, which was associated with increased tumor survival. Inhibition of HTR2B activity resulted in the suppression of tumor growth through modulation of the G2M cell cycle. The inhibition of HTR2B with PRX-08066 was found to block STAT3 phosphorylation and nuclear translocation by interfering with the Gαq/PLC/PKC pathway. A direct interaction between PKC-γ and STAT3 was critical for STAT3 activation. CAB was shown to activate pSTAT3 via HTR2B, reducing its therapeutic potential. However, the combination of an HTR2B antagonist with CAB significantly inhibited tumor cell proliferation in HTR2B-expressing pituitary tumor cell lines, a xenografted pituitary tumor model, and patient-derived samples. Analysis of patient-derived data indicated that a distinct molecular pattern characterized by upregulated HTR2B/PKC-γ and downregulated BTG2/GADD45A may benefit from combination treatment with CAB and PRX-08066. CONCLUSIONS: HTR2B is a potential therapeutic target for NFPAs, and its inhibition could improve CAB efficacy. A dual therapy approach may be beneficial for NFPA patients with high HTR2B expression.

Physical Adversarial Attack Meets Computer Vision: A Decade Survey.

Despite the impressive achievements of Deep Neural Networks (DNNs) in computer vision, their vulnerability to adversarial attacks remains a critical concern. Extensive research has demonstrated that incorporating sophisticated perturbations into input images can lead to a catastrophic degradation in DNNs' performance. This perplexing phenomenon not only exists in the digital space but also in the physical world. Consequently, it becomes imperative to evaluate the security of DNNs-based systems to ensure their safe deployment in real-world scenarios, particularly in security-sensitive applications. To facilitate a profound understanding of this topic, this paper presents a comprehensive overview of physical adversarial attacks. Firstly, we distill four general steps for launching physical adversarial attacks. Building upon this foundation, we uncover the pervasive role of artifacts carrying adversarial perturbations in the physical world. These artifacts influence each step. To denote them, we introduce a new term: adversarial medium. Then, we take the first step to systematically evaluate the performance of physical adversarial attacks, taking the adversarial medium as a first attempt. Our proposed evaluation metric, hiPAA, comprises six perspectives: Effectiveness, Stealthiness, Robustness, Practicability, Aesthetics, and Economics. We also provide comparative results across task categories, together with insightful observations and suggestions for future research directions.

EBV-positive small cell neuroendocrine carcinoma of nasopharynx as a probably unique subtype of neuroendocrine carcinoma: a clinicopathologic study of three cases and literature review.

BACKGROUND: There is currently scarcity of information on small cell neuroendocrine carcinoma of the nasopharynx (SCNEC-nasopharynx). It is believed that this type of cancer is not associated with Epstein-Barr virus (EBV) infection and is indistinguishable from classic SCNEC occurring in other organs. MATERIALS AND METHODS: Herein we provided 3 cases of nasopharyngeal mass in our hospital, two males and one female. On admission, these patients were considered nasopharyngeal carcinoma with lymph node metastasis, and one of them had liver metastasis. The nasopharyngeal mucosal tissues were biopsied for pathological examination including immunohistochemistry and in situ hybridization. PubMed database was searched for articles about SCNEC-nasopharynx published up to April 2024 in any language. RESULT: The 3 cases had similar histological features of SCNEC in other organs but differed in rich- tumor-infiltrating lymphocytes (TILs). All of them stained for pancytokeratin (panCK) and epidermal growth factor receptor (EGFR). Case 1 and Case 2 diffusely expressed insulinoma-associated protein 1(INSM-1) and synaptophysin (Syn), Case 3 strongly stained for CD56 and Syn. Immunostaining of all 3 cases for p40, p63, TTF-1, CK20, S-100 and NUT showed negative. BRG-1, INI-1 and Rb were retained. And p53 all showed wild-type expression. The Ki-67 labeling indiced of case 1, 2, and 3 were 80%, 90%, and 80%, respectively. In situ hybridization showed strong and uniform nuclear positivity of EBV-encoded small RNAs (EBER) in the neoplastic cells of 3 cases. CONCLUSION: EBV-positive SCNEC-nasopharynx was exactly rare. The origin of this tumor is still controversial. It may originate from EBV-infected mucosal epithelium like nasopharyngeal carcinoma. Based on our cases and relevant literature, we found EBV-positive SCNEC-nasopharynx as a probably site-specific subtype of SCNEC with differing pathogenetic mechanism. The subtype not only virus positivity but also that it was associated with TILs and did not show p53 or Rb alterations by immunohistochemistry. It may be more responsive to treatment and have a better prognosis than classic SCNEC. We will continue to follow-up these patients and collect additional cases to further understand the unique biology of this rare solid tumor.

Baicalin promotes the sensitivity of NSCLC to cisplatin by regulating ferritinophagy and macrophage immunity through the KEAP1-NRF2/HO-1 pathway.

BACKGROUND: Cisplatin (DDP) chemotherapy is commonly used in therapy for non-small cell lung cancer (NSCLC), but increased drug resistance has become a huge obstacle. Baicalin (BA) contributed to the sensitivity of NSCLC to DDP. Here, we aimed to further probe the pathophysiological mechanisms of BA in NSCLC. METHODS: A549 and A549/DDP cells and xenograft mice were treated with BA and DDP. Xenograft mice were treated additionally with the NRF2 inducer (Bardoxolone methyl, BM) and KEAP1 knockdown. The levels of ferritinophagy-related proteins and biomarkers were determined. The autophagosomes were observed. M1 macrophage polarization and the contents of related indicators were analyzed. The involvement of KEAP1/NRF2/HO-1 was determined. RESULTS: BA inhibited cell development, and the effect of BA and DDP on cell development was additive. The abundance of ferritinophagy-related proteins and the number of autophagosomes were induced by BA. BA also promoted the transition of GSH to GSSH. BA favored M1 macrophage polarization and affected the expression of related proteins. When BA and DDP combined, these molecular phenomena were further exacerbated. BA induced accumulation of KEAP1 and reduction of NRF2 and HO-1. However, BM and KEAP1 knockdown disrupted the synergistic effects of BA and DDP on inhibiting NSCLC growth. BM and KEAP1 knockdown reversed DDP and BA-promoted protein expression activity and M1 macrophage polarization. CONCLUSION: Our findings suggest that BA is involved in ferritinophagy and macrophage immunity through the KEAP1-NRF2/HO-1 axis, thereby improving the DDP sensitivity in NSCLC, which could provide new candidates for treatment strategies.

A Frequency Up-Conversion Piezoelectric Energy Harvester Shunted to a Synchronous Electric Charge Extraction Circuit.

A frequency up-conversion piezoelectric energy harvester (FUC-PEH) consists of a force amplifier, a piezoelectric stack, a low-frequency oscillator (LFO), and a stop limiter. The force amplifier generates the amplification of stress on the piezoelectric stack. The LFO, comprising a spring and a mass block, impacts the stop limiter during vibration to induce high-frequency oscillations within the piezoelectric stack. In this paper, we represent and simplify the FUC-PEH as a lumped-parameter model based on piezoelectric material constitutive equations and structural dynamic theories. Using the electromechanical analogy, we developed an equivalent circuit model (ECM) of the FUC-PEH. A parametric study was performed to investigate the impact of system parameters, such as spring stiffness and concentrated mass, on the FUC-PEH performance. The collision-induced amplitude truncation (AT) effect enlarges the operation bandwidth. ECM simulations show that low-frequency input excitation is converted into a high-frequency output response, enhancing the energy conversion efficiency. Furthermore, we aimed to improve the FUC-PEH's performance using a synchronous electric charge extraction (SECE) circuit. Using the ECM approach, we established a system-level model that considers the electromechanical coupling behavior. The simulation results provide insights into the performance of FUC harvesters with SECE circuits and offer valuable design guidance.

Green investor behavior and corporate green innovation: Evidence from Chinese listed companies.

Businesses embracing green innovation can encourage high-quality green economic development in addition to reducing emissions. In this paper, we use the Difference-in-Differences (DID) to investigate the influence of green investor behavior on the green innovation of companies, using the first-ever green investor investment in a company as a quasi-natural experiment. According to research, green investors have the power to accelerate corporate green innovation greatly. Three key strategies that green investors can use to do this include raising institutional investment levels, enhancing the green perception of executives, and bringing in top talent. Heterogeneity analysis shows that non-high-polluting, big, and state-owned enterprises (SOEs) are more likely to benefit from green investors' green innovation effects. Further analysis reveals that (ⅰ) green investors' influence on an enterprise's level of green innovation can help it improve its ESG ratings; (ii) green investors can encourage green innovation in source control but have little effect on green innovation in end-of-pipe treatment; (ⅲ) green investors can support both non-green and green innovation in enterprises, but have a greater influence on green innovation. This study strengthens the micro relationship between green investors and corporate green innovation. It also supports the theoretical underpinnings of corporate green innovation, which is significant for advancing green innovation, environmental protection, and high-quality economic development in emerging economies.

3D matrix stiffness modulation unveils cardiac fibroblast phenotypic switching.

This study investigates how dynamic fluctuations in matrix stiffness affect the behavior of cardiac fibroblasts (CFs) within a three-dimensional (3D) hydrogel environment. Using hybrid hydrogels with tunable stiffness, we created an in vitro model to mimic the varying stiffness of the cardiac microenvironment. By manipulating hydrogel stiffness, we examined CF responses, particularly the expression of α-smooth muscle actin (α-SMA), a marker of myofibroblast differentiation. Our findings reveal that increased matrix stiffness promotes the differentiation of CFs into myofibroblasts, while matrix softening reverses this process. Additionally, we identified the role of focal adhesions and integrin ß1 in mediating stiffness-induced phenotypic switching. This study provides significant insights into the mechanobiology of cardiac fibrosis and suggests that modulating matrix stiffness could be a potential therapeutic strategy for treating cardiovascular diseases.