A Prospective Self-controlled Clinical Trial of Nonactivated Low Leukocyte PRP in Female Pattern Hair Loss Patients of Childbearing Age.

BACKGROUND: Alopecia significantly affects the mental health and social relationship of women since childbearing age, highlighting the need for a safe, effective, and convenient treatment. METHODS: The authors have conducted a prospective self-controlled trial involving 15 female patients at childbearing age with alopecia. These patients received a subcutaneous scalp injection of platelet-rich plasma once every 4 weeks for 3 treatments in total. Outcome measurements were included below: changes in hair density (hair/cm2), hair follicle density (hair follicle/cm2), and overall photographic assessment (improved or not) at 4, 12, and 24 weeks right after the first treatment. RESULTS: Comparing the photographs taken before and after the intervention, 67% of patients' hair density increased from 151 ± 39.82 hairs/cm2 (preintervention) to 170.96 ± 37.14 hairs/cm2 (at 24-week follow-up), representing an approximate increase of 19 hairs/cm2. Meanwhile, hair follicle density increased by approximately 15 follicles/cm2 after 24 weeks since the first treatment, rising from 151.04 ± 41.99 follicles/cm2 to 166.72 ± 37.13 follicles/cm2. The primary adverse reactions observed were local swelling and pain due to injections. CONCLUSION: Local injection of nonactivated platelet-rich plasma with low leukocytes concentration could be an effective strategy to alleviate alopecia symptoms in female patients.

Research progress on the role of p53 in pulmonary arterial hypertension.

PURPOSE OF REVIEW: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by increased pulmonary vascular resistance and pulmonary arterial pressure. At present, the definitive pathology of PAH has not been elucidated and its effective treatment remains lacking. Despite PAHs having multiple pathogeneses, the cancer-like characteristics of cells have been considered the main reason for PAH progression. RECENT FINDINGS: p53 protein, an important tumor suppressor, regulates a multitude of gene expressions to maintain normal cellular functions and suppress the progression of malignant tumors. Recently, p53 has been found to exert multiple biological effects on cardiovascular diseases. Since PAH shares similar metabolic features with cancer cells, the regulatory roles of p53 in PAH are mainly the induction of cell cycle, inhibition of cell proliferation, and promotion of apoptosis. SUMMARY: This paper summarized the advanced findings on the molecular mechanisms and regulatory functions of p53 in PAH, aiming to reveal the potential therapeutic targets for PAH.

A conjugate vaccine strategy that induces protective immunity against arecoline.

Betel-quid chewing addiction is the leading cause of oral submucous fibrosis and oral cancer, resulting in significant socio-economic burdens. Vaccination may serve as a promising potential remedy to mitigate the abuse and combat accidental overdose of betel nut. Hapten design is the crucial factor to the development of arecoline vaccine that determines the efficacy of a candidate vaccine. Herein, we reported that two kinds of novel arecoline-based haptens were synthesized and conjugated to Bovine Serum Albumin (BSA) to generate immunogens, which generated antibodies with high affinity for arecoline but reduced binding for guvacoline and no affinity for arecaidine or guvacine. Notably, vaccination with Arec-N-BSA, which via the N-position on the tetrahydropyridine ring (tertiary amine group), led to a higher antibody affinity compared to Arec-CONH-BSA, blunted analgesia and attenuated hypothermia for arecoline.

Oleic acid-PPARγ-FABP4 loop fuels cholangiocarcinoma colonization in lymph node metastases microenvironment.

BACKGROUND AND AIMS: Lymph node metastasis is a significant risk factor for patients with cholangiocarcinoma, but the mechanisms underlying cholangiocarcinoma colonization in the lymph node microenvironment remain unclear. We aimed to determine whether metabolic reprogramming fueled the adaptation and remodeling of cholangiocarcinoma cells to the lymph node microenvironment. APPROACH AND RESULTS: Here, we applied single-cell RNA sequencing of primary tumor lesions and paired lymph node metastases from patients with cholangiocarcinoma and revealed significantly reduced intertumor heterogeneity and syntropic lipid metabolic reprogramming of cholangiocarcinoma after metastasis to lymph nodes, which was verified by pan-cancer single-cell RNA sequencing analysis, highlighting the essential role of lipid metabolism in tumor colonization in lymph nodes. Metabolomics and in vivo CRISPR/Cas9 screening identified PPARγ as a crucial regulator in fueling cholangiocarcinoma colonization in lymph nodes through the oleic acid-PPARγ-fatty acid-binding protein 4 positive feedback loop by upregulating fatty acid uptake and oxidation. Patient-derived organoids and animal models have demonstrated that blocking this loop impairs cholangiocarcinoma proliferation and colonization in the lymph node microenvironment and is superior to systemic inhibition of fatty acid oxidation. PPARγ-regulated fatty acid metabolic reprogramming in cholangiocarcinoma also contributes to the immune-suppressive niche in lymph node metastases by producing kynurenine and was found to be associated with tumor relapse, immune-suppressive lymph node microenvironment, and poor immune checkpoint blockade response. CONCLUSIONS: Our results reveal the role of the oleic acid-PPARγ-fatty acid-binding protein 4 loop in fueling cholangiocarcinoma colonization in lymph nodes and demonstrate that PPARγ-regulated lipid metabolic reprogramming is a promising therapeutic target for relieving cholangiocarcinoma lymph node metastasis burden and reducing further progression.

Lizhong decoction ameliorates ulcerative colitis by inhibiting ferroptosis of enterocytes via the Nrf2/SLC7A11/GPX4 pathway.

ETHNOPHARMACOLOGY RELEVANCE: Traditional herbal medicines have been considered as a novel and effective way to treat many diseases. Lizhong decoction (LZD), a classical prescription composed of Zingiber officinale Rosc., Panax ginseng C. A. Mey., Atractylodes macrocephala Koidz., and Glycyrrhiza uralensis Fisch., has been used to treat gastrointestinal disorders in clinical practices for thousands of years. However, the mechanism of LZD in alleviating ulcerative colitis (UC) is still unclear. AIM OF THE STUDY: The purpose of this study was to clarify the potential molecular mechanism of LZD in improving UC. MATERIALS AND METHODS: The amelioration of LZD on dextran sodium sulfate (DSS)-induced UC mice was evaluated by body weight, colon length, pathology of colon tissues, pro-inflammatory cytokines, and intestinal tight junction (TJ) proteins. Moreover, the gene expression profiles of UC patients were extracted to investigate potential pathological mechanisms of UC. The influence of LZD on ferroptosis was analyzed by iron load, malondialdehyde (MDA), and the expression of ferroptosis-associated proteins. Meanwhile, the inhibition of LZD on oxidative stress (OS) was assessed by the superoxide dismutase (SOD) activity, as well as the expression levels of glutathione (GSH) and glutathione disulfide (GSSG). Furthermore, the influence of LZD on ferroptosis was assessed by inhibiting nuclear factor (erythroid-derived-2)-like 2 (Nrf2). RESULTS: LZD showed significant therapeutic effects in UC mice, including reduction of intestinal injury and inflammation. Moreover, LZD treatment notably upregulated the expression of TJ proteins. Further investigation indicated that LZD significantly inhibited the ferroptosis of enterocytes by decreasing iron load and MDA, and increasing the expression levels of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in colon tissues. Furthermore, the decreased activity of SOD, reduced level of GSH, and increased content of GSSG in UC mice were notably reversed by LZD. Consistent with in vivo results, LZD could markedly inhibit ferroptosis and OS in RSL3-induced Caco-2 cells. Mechanistically, LZD alleviated ferroptosis by suppressing OS through the activation of Nrf2 signaling. CONCLUSIONS: Collectively, LZD remarkably improved intestinal pathological injury in UC mice, and its potential mechanism was the suppression of ferroptosis in enterocytes by the Nrf2/SLC7A11/GPX4 pathway.

Platelet-to-Lymphocyte Ratio (PLR), Neutrophil-to-Lymphocyte Ratio (NLR), Monocyte-to-Lymphocyte Ratio (MLR), and Eosinophil-to-Lymphocyte Ratio (ELR) as Biomarkers in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD).

Purpose: The study comprehensively evaluated the prognostic roles of the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), basophil-to-lymphocyte ratio (BLR), and eosinophil-to-lymphocyte ratio (ELR) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Patients and Methods: Six hundred and nineteen patients with AECOPD and 300 healthy volunteers were retrospectively included into the study. The clinical characteristics of the patients with AECOPD and the complete blood counts (CBCs) of the healthy volunteers were collected. The associations of PLR, NLR, MLR, BLR, and ELR with airflow limitation, hospital length of stay (LOS), C-reactive protein (CRP), and in-hospital mortality in patients with AECOPD were analyzed. Results: Compared with the healthy volunteers, PLR, NLR, MLR, BLR, and ELR were all elevated in COPD patients under stable condition. PLR, NLR, MLR, and BLR were further elevated while ELR was lowered during exacerbation. In the patients with AECOPD, PLR, NLR, and MLR were positively correlated with hospital LOS as well as CRP. In contrast, ELR was negatively correlated with hospital LOS as well as CRP. Elevated PLR, NLR, and MLR were all associated with more severe airflow limitation in AECOPD. Elevated PLR, NLR, and MLR were all associated with increased in-hospital mortality while elevated ELR was associated with decreased in-hospital mortality. Binary logistic regression analysis showed that smoking history, FEV1% predicted, pneumonia, pulmonary heart disease (PHD), uric acid (UA), albumin, and MLR were significant independent predictors ofin-hospital mortality. These predictors along with ELR were used to construct a nomogram for predicting in-hospital mortality in AECOPD. The nomogram had a C-index of 0.850 (95% CI: 0.799-0.901), and the calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) further demonstrated its good predictive value and clinical applicability. Conclusion: In summary, PLR, NLR, MLR, and ELR served as useful biomarkers in patients with AECOPD.

Phenotypic and genotypic characterization of Marinobacterium weihaiense sp. nov. and Marinobacterium marinum sp. nov., isolated from marine sediment, and genomic properties of the genus Marinobacterium.

In this study, two novel bacterial strains were isolated from coastal sediment of Weihai, China. The two strains were Gram-stain-negative and facultatively aerobic, designated 3-1745T and A346T. Based on phenotypic, genetic and phylogenetic properties, strains 3-1745T and A346T represent two novel species of the genus Marinobacterium. The results of genome analysis revealed many central carbohydrate metabolism pathways such as gluconeogenesis, pyruvate oxidation, tricyclic acid cycle, pentose phosphate pathway and PRPP biosynthesis in the genus Marinobacterium. The ability of strains 3-1745T and A346T to utilize volatile fatty acids was experimentally confirmed. Polyhydroxyalkanoate synthases (PhaA, PhaB and PhaC) for the synthesis of polyhydroxyalkanoates were prevalent in the genus Marinobacterium. Multiple BGCs (biosynthetic gene clusters) including betalactone, ectoine, ranthipeptide, redox-cofactor, RiPPs (ribosomally synthesized post-translationally modified peptides) and T3PKS (polyketide synthases) in the genome of the genus Marinobacterium were found. Additional genome analyses suggested that the genus Marinobacterium contained diverse potential mechanisms of salt tolerance and mainly utilized oligosaccharides. This is the first report on broad genomic analyses of the genus Marinobacterium with the description of two novel species and potential ecological and biotechnological implications.

Tasquinimod enhances the sensitivity of ovarian cancer cells to cisplatin by regulating the Nur77-Bcl-2 apoptotic pathway.

BACKGROUND: Resistance to cisplatin (DDP) in ovarian cancer therapy has been a major clinical barrier. Drug-resistant cancers have been shown to downregulate the proapoptotic protein B-cell lymphoma-2 (Bcl-2) to inhibit apoptosis. Therefore, we explored whether tasquinimod could modulate resistance to DDP through apoptotic pathways. OBJECTIVES: We aimed to explore the relationship between tasquinimod, Nur77-Bcl-2 apoptosis pathway and sensitivity of the ovarian carcinoma cell line SKOV3 and the DDP-resistant strain SKOV3/DDP cells to DDP. MATERIAL AND METHODS: First, SKOV3 and SKOV3/DDP cells were treated with 2 µg/mL DDP or 40 µM tasquinimod. Western blot and quantitative real-time polymerase chain reaction (qPCR) were then used to analyze the expression of histone deacetylase 4 (HDAC4), Nur77, Bcl-2 (BH3 domain-specific), and caspase-3. Flow cytometry, scratch-wound assay and immunofluorescence were used to detect apoptosis, migration rate, and related expression of Nur77 and Bcl-2 (BH3 domain-specific). Subsequently, 5×107 SKOV3 or SKOV3/DDP cells cultured with 2 µg/mL DDP were injected into 4-week-old female BALB/c nude mice. Then, the mice were administered 4 mg/kg DDP and 50 mg/kg tasquinimod every 3 days. Finally, the changes in tumor diameter and weight were measured. RESULTS: After treatment of SKOV3 and SKOV3/DDP cells with tasquinimod, cell migration and HDAC4 expression levels were significantly reduced, while Nur77 expression was increased. Tasquinimod treatment enhanced the expression of Nur77 and caspase-3, and cells transfected with si-Nur77 showed the opposite result. Transfection of si-Nur77 reduced the expression of caspase-3 and Nur77 in the SKOV3/DDP cells that were treated with both DDP and tasquinimod. After injection of SKOV3/DDP cells into the mice, the tumor diameter, mass and in vivo HDAC4 level were significantly decreased by tasquinimod. Meanwhile, the levels of Nur77 and Bcl-2 (BH3 domain-specific) were increased. CONCLUSIONS: Tasquinimod upregulated the Nur77/Bcl-2 pathway to induce apoptosis in SKOV3/DDP cells and enhanced the anti-tumor effect of DDP in SKOV3/DDP xenografts. Therefore, tasquinimod can be expected to find clinical applications in enhancing DDP resistance.

Diverse Metabolic Effects of Cooking Oil Fume from Four Edible Oils on Human BEAS-2B Cells: Implications for Health Guidelines.

The 2021 WHO guidelines stress the importance of measuring ultrafine particles using particle number concentration (PNC) for health assessments. However, commonly used particle metrics such as aerodynamic diameter and number concentrations do not fully capture the diverse chemical makeup of complex particles. To address this issue, our study used high-throughput mass spectrometry to analyze the properties of cooking oil fumes (COFs) in real time and evaluate their impact on BEAS-2B cell metabolism. Results showed insignificant differences in COF number size distributions between soybean oil and olive oil (peak concentrations of 5.20 × 105/cm3), as well as between corn oil and peanut oil (peak concentrations of 4.35 × 105/cm3). Despite the similar major chemical components among the four COFs, variations in metabolic damage were observed, indicating that the relatively small amount of chemical components of COFs can also influence particle behavior within the respiratory system, thereby impacting biological responses. Additionally, interactions between accompanying gaseous COFs and particles may alter their chemical composition through various mechanisms, introducing additional chemicals and modifying existing proportions. Hence, the chemical composition and gaseous components of COFs hold equal importance to the particle number concentration (PNC) when assessing their impact on human health. The absence of these considerations in the current guidelines underscores a research gap. It is imperative to acknowledge that for a more comprehensive approach to safeguarding public health, guidelines must be regularly updated to reflect new scientific findings and robust epidemiological evidence.

Humidity-controlled heat treatment of fresh spinach noodles for color preservation and storage quality improvement.

The high sensitivity to color browning during room-temperature storage was a significant factor in limiting the development of fresh spinach noodles (FSN). The practice of humidity-controlled heat treatment (HCHT) at varying temperatures, relative humidity, and time was carried out to limit enzyme activity and improve the quality of FSN. Results showed that HCHT could maximize the color preservation of fresh spinach noodle quality while effectively inactivating polyphenol oxidase and the yeasts, and mold count in FSN during storage was almost undetectable after mild conditions (80 °C). The hardness and chewiness of HCHT noodles were significantly increased, but the free sulfhydryl content was reduced. At 80 °C, 90 %, 5 min, protein structural aggregation was found in the microstructure of HCHT fresh spinach noodles. HCHT also caused partial gelatinization, as evidenced by the decrease in starch gelatinization enthalpy from 5.49 to 4.77 J/g, although the gelatinization degree of FSN was comparatively low.

A Notch signaling-related lncRNA signature for predicting prognosis and therapeutic response in clear cell renal cell carcinoma.

Increasing evidence has confirmed the vital role of Notch signaling in the tumorigenesis of clear cell renal cell carcinoma (ccRCC). The underlying function of long non-coding RNA (lncRNA) related to Notch signaling in ccRCC remains unclear. In present study, the prognostic value and therapeutic strategy of Notch signaling-related lncRNA are comprehensively explored in ccRCC. In total, we acquired 1422 NSRlncRNAs, of which 41 lncRNAs were identified the key NSRlncRNAs associated with the occurrence of ccRCC. The prognostic signature containing five NSRlncRNAs (AC092611.2, NNT-AS1, AGAP2-AS1, AC147651.3, and AC007406.3) was established and validated, and the ccRCC patients were clustered into the high- and low-risk groups. The overall survival of patients in the low-risk group were much more favorable than those in the high-risk group. Multivariate Cox regression analysis indicated that the risk score was an independent prognostic biomarker. Based on the risk score and clinical variables, a nomogram for predicting prognosis of ccRCC patients was constructed, and the calibration curves and DCA curves showed the superior predictive ability of nomogram. The risk score was correlated with immune cell infiltration, targeted therapy or chemotherapy sensitivity, and multiple oncogenic pathways. Additionally, consensus clustering analysis stratified the ccRCC patients into four clusters with obvious different outcomes, immune microenvironments, and expression of immune checkpoints. The constructed NSRlncRNA-based signature might serve as a potential biomarker for predicting prognosis and response to immunotherapy or targeted therapy in patients with ccRCC.

Characterization of Biodiesel and Diesel Combustion Particles: Chemical Composition, Lipid Metabolism, and Implications for Health and Environment.

Biodiesel, derived from alkyl esters of vegetable oils or animal fats, has gained prominence as a greener alternative to diesel due to its reduced particle mass. However, it remains debatable whether biodiesel exposure has more severe health issues than diesel. This study performed high-resolution mass spectrometry to examine the detailed particle chemical compositions and lipidomics analysis of human lung epithelial cells treated with emissions from biodiesel and diesel fuels. Results show the presence of the peak substances of CHO compounds in biodiesel combustion that contain a phthalate ester (PAEs) structure (e.g., n-amyl isoamyl phthalate and diisobutyl phthalate). PAEs have emerged as persistent organic pollutants across various environmental media and are known to possess endocrine-disrupting properties in the environment. We further observed that biodiesel prevents triglyceride storage compared to diesel and inhibits triglycerides from becoming phospholipids, particularly with increased phosphatidylglycerols (PGs) and phosphatidylethanolamines (PEs), which potentially could lead to a higher probability of cancer metastasis.

Influence of Polycyclic Aromatic Compounds and Oxidation States of Soot Organics on the Metabolome of Human-Lung Cells (A549): Implications for Vehicle Fuel Selection.

Decades of research have established the toxicity of soot particles resulting from incomplete combustion. However, the unique chemical compounds responsible for adverse health effects have remained uncertain. This study utilized mass spectrometry to analyze the chemical composition of extracted soot organics at three oxidation states, aiming to establish quantitative relationships between potentially toxic chemicals and their impact on human alveolar basal epithelial cells (A549) through metabolomics-based evaluations. Targeted analysis using MS/MS indicated that particles with a medium oxidation state contained the highest total abundance of compounds, particularly oxygen-containing polycyclic aromatic hydrocarbons (OPAHs) composed of fused benzene rings and unsaturated carbonyls, which may cause oxidative stress, characterized by the upregulation of three specific metabolites. Further investigation focused on three specific OPAH standards: 1,4-naphthoquinone, 9-fluorenone, and anthranone. Pathway analysis indicated that exposure to these compounds affected transcriptional functions, the tricarboxylic acid cycle, cell proliferation, and the oxidative stress response. Biodiesel combustion emissions had higher concentrations of PAHs, OPAHs, and nitrogen-containing PAHs (NPAHs) compared with other fuels. Quinones and 9,10-anthraquinone were identified as the dominant compounds within the OPAH category. This knowledge enhances our understanding of the compounds contributing to adverse health effects observed in epidemiological studies and highlights the role of aerosol composition in toxicity.

Identification of a Novel Prognostic Signature Based on N-Linked Glycosylation and Its Correlation with Immunotherapy Response in Hepatocellular Carcinoma.

Background: The complex tumor microenvironment of hepatocellular carcinoma (HCC) has led to a low response to immune checkpoints inhibitors (ICIs) and a poor prognosis. PD-L1, as one of the indications for ICIs, is rich in glycosylation modifications, which result in untimely ICIs. Our study constructed a prognostic model based on N-linked glycosylation related genes for predicting the prognosis and the response to ICIs. Methods: The list of N-linked glycosylation related genes is from the AmiGO2 database. The patients in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts were enrolled. The Cox regression was performed to develop a prognostic model and patients were divided into a low- and high-risk subgroups. The role of signature in HCC was well investigated by prognostic analysis, gene set enrichment analysis, and immune infiltration analysis. 21 recurrent HCC patients who received postoperative adjuvant ICIs were recruited to evaluate the relationship between immunotherapy response and the signature. In vitro studies were conducted to investigate the oncogenic effects of DDOST, STT3A and TMEM165 in HCC. Results: 59 N-linked glycosylation related differentially expressed genes were screened from HCC and normal tissues in the TCGA cohort. The prognostic model was developed with DDOST, STT3A and TMEM165. The risk score could be an independent prognostic factor. Patients in the high-risk subgroup showed a worse prognosis than patients in the low-risk one. ssGSEA showed that patients in the low-risk subgroup tended to be in the immune-activated state, with higher levels of B cell and macrophage cell infiltrations and lower levels of regulatory T cell (Treg) infiltrations in both TCGC and GEO cohorts. Immunohistochemistry studies showed that DDOST, STT3A and TMEM165 are highly expressed in tumor tissues and patients with a high-risk score correlated with poor progression free survival and worse immunotherapeutic response. Furthermore, the proliferation of HCC cells was reduced after the knockdown of DDOST, as well as upon the knockdown of STT3A and TMEM165. Conclusion: In this study, we establish that the risk model based on N-linked glycosylation related genes could efficiently predict the prognosis and tumor microenvironment immune state of HCC patients, and the risk score could serve as a novel indicator of immunotherapy.

The microprotein encoded by exosomal lncAKR1C2 promotes gastric cancer lymph node metastasis by regulating fatty acid metabolism.

Lymph node metastasis (LNM) is the prominent route of gastric cancer dissemination, and usually leads to tumor progression and a dismal prognosis of gastric cancer. Although exosomal lncRNAs have been reported to be involved in tumor development, whether secreted lncRNAs can encode peptides in recipient cells remains unknown. Here, we identified an exosomal lncRNA (lncAKR1C2) that was clinically correlated with lymph node metastasis in gastric cancer in a VEGFC-independent manner. Exo-lncAKR1C2 secreted from gastric cancer cells was demonstrated to enhance tube formation and migration of lymphatic endothelial cells, and facilitate lymphangiogenesis and lymphatic metastasis in vivo. By comparing the metabolic characteristics of LN metastases and primary focuses, we found that LN metastases of gastric cancer displayed higher lipid metabolic activity. Moreover, exo-lncAKR1C2 encodes a microprotein (pep-AKR1C2) in lymphatic endothelial cells and promotes CPT1A expression by regulating YAP phosphorylation, leading to enhanced fatty acid oxidation (FAO) and ATP production. These findings highlight a novel mechanism of LNM and suggest that the microprotein encoded by exosomal lncAKR1C2 serves as a therapeutic target for advanced gastric cancer.

Cyanidin-3-O-glucoside Mitigates the Ovarian Defect Induced by Zearalenone via p53-GADD45a Signaling during Primordial Follicle Assembly.

Zearalenone (ZEN) is well known as a kind of endocrine disruptor whose exposure is capable of causing reproductive toxicity in animals. Cyanidin-3-O-glucoside (C3G) is a derivative of cyanidin and owns multiple biofunctions, and prior efforts have suggested that C3G has therapeutic actions for reproductive diseases. In this article, a ZEN exposure model during primordial follicle assembly was constructed using the in vitro culture platform of neonatal mouse ovaries. We investigated the protective effect of C3G on ZEN-induced ovarian toxicity during primordial follicle assembly in mice, as well as its potential mechanism. Interestingly, we observed that C3G could effectively protect the ovary from ZEN damage, mainly by restoring primordial follicle assembly, which upregulated the expression of LHX8 and SOHLH1 proteins and relieved ZEN-induced DNA damage. Next, to explore the mechanism by which C3G rescued ZEN-induced injury, we performed RNA sequencing (RNA-seq). The bioinformatic analysis illustrated that the rescue pathway of C3G was associated with p53-Gadd45a signaling and cell cycle. Then, western blotting and flow cytometry results revealed that C3G restored the expression levels of cyclin-dependent kinase 6 (CDK6) and cyclin D2 (CCND2) and regulated the ovarian cell cycle to normal. In conclusion, our findings manifested that C3G could alleviate ZEN-induced primordial follicle assembly impairment by restoring the cell cycle involved in p53-GADD45a signaling.

Tongue texture may contribute to the assessment of malignant risk of thyroid nodules.

In the present study, it was aimed to evaluate whether there is an objective tongue image indicator that could be used to evaluate malignant risk of thyroid nodules through a cross sectional study. From December 2018 to December 2020, the TFDA-1 digital tongue-face diagnostic instrument was used to collect the tongue images. TDAS 2.0 software was used for tongue image analysis. A standardized database was constructed by combining patient physical examination results and tongue image analysis results. The relationship between tongue image index and TI-RADS classification of thyroid nodules was tested. A total of 5,900 cases were collected and 4,615 cases were included in the present study after excluding 154 cases due to incomplete information, 1,221 cases with thyroid nodules were separated into 417 cases TI-RADS 2 group, 693 cases in TI-RADS 3 group and 111 cases in TI-RADS 4 group. Without considering confounding factors, tongue image indexes zhiCon, zhiASM, zhiENT, zhiMEAN, zhiClrB, zhiClrR, zhiClrG, zhiClrI, zhiClrL and zhiClrY were significantly different among the three groups (P<0.05). Excluding the influence of age, sex, body mass index, smoking and drinking, the results of one-way variance linear trend analysis showed that the values of zhiCon, zhiENT and zhiMEAN increased with the increasing TI-RADS category, while the values of zhiASM decreased with the increase of TI-RADS category. Tongue texture index may be helpful for differentiating the benign and malignant of thyroid nodules.

Eukaryotic translation initiation factor 2α kinase 2 in pancreatic cancer: An approach towards managing clinical prognosis and molecular immunological characterization.

Most patients with pancreatic cancer are already in the late stages of the disease when they are diagnosed, and pancreatic cancer is a deadly disease with a poor prognosis. With the advancement of research, immunotherapy has become a new focus in the treatment of tumors. To the best of our knowledge, there is currently no reliable diagnostic or prognostic marker for pancreatic cancer; therefore, the present study investigated the potential of eukaryotic translation initiation factor 2α kinase 2 (EIF2AK2) as a predictive and diagnostic marker for pancreatic cancer. Immunohistochemical staining of clinical samples independently verified that EIF2AK2 expression was significantly higher in clinically operated pancreatic cancer tissues than in adjacent pancreatic tissues., and EIF2AK2 expression and differentially expressed genes (DEGs) were identified using downloadable RNA sequencing data from The Cancer Genome Atlas and Genomic Tumor Expression Atlas. In addition, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analyses and immune cell infiltration were used for functional enrichment analysis of EIF2AK2-associated DEGs. The clinical importance of EIF2AK2 was also determined using Kaplan-Meier survival, Cox regression and time-dependent survival receiver operating characteristic curve analyses, and a predictive nomogram model was generated. Finally, the functional role of EIF2AK2 was assessed in PANC-1 cells using a short hairpin RNA-EIF2AK2 knockdown approach, including CCK-8, wound healing assay, cell cycle and apoptosis assays. The findings suggested that EIF2AK2 may have potential as a diagnostic and prognostic biomarker for patients with pancreatic cancer. Furthermore, EIF2AK2 may provide a new therapeutic target for patients with pancreatic cancer.

Small airway dysfunction associated with poor short-term outcomes in patients undergoing thoracoscopic surgery for lung cancer.

BACKGROUND: Although small airway dysfunction is a common respiratory dysfunction, its prognosis after lung cancer surgery is often neglected. This study investigated the relationship between small airway dysfunction and outcomes in patients who underwent thoracoscopic surgery for lung cancer. METHODS: A retrospective cohort study of patients who underwent thoracoscopic surgery was conducted between December 2019 and March 2021 at Ningbo First Hospital. We used univariate and multivariate analyses to assess the possible associations between postoperative outcomes and clinical variables, including small airway dysfunction. To balance the potential confounding factors, propensity score matching was performed to establish 1:1 small airway dysfunction and small airway normal function group matching. RESULTS: In this study, 1,012 patients undergoing thoracoscopic surgery for lung cancer were enrolled. Small airway dysfunction was present in 18.7% of patients (189/1,012). The incidence of postoperative pulmonary complications in the small airway dysfunction group was higher than that of the small airway normal function group (16.4% vs 6.2%, P < .001). The most significant postoperative pulmonary complications were pneumonia (7.4% vs 2.4%, P < .001) in the small airway dysfunction and normal function groups, respectively. In addition, a significantly prolonged median hospital length of stay was observed in the small airway dysfunction group compared to the small airway normal function group (median [interquartile range], 9 [7-12] vs 8 [7-9], P < .001). After 1:1 propensity score matching, 298 patients (149 pairs) were included in the comparison between small airway dysfunction and small airway normal function, and this association remained. Postoperative pulmonary complications (13.4% vs 6.0%, P = .032) were still higher, and length of stay (median [interquartile range] 9 [7-11] vs 8 [6-10] days, P = .001) was still longer in the small airway dysfunction group. Multivariate analysis indicated that small airway dysfunction was the independent risk factor associated with both postoperative pulmonary complications (odds ratio = 2.694, 95% confidence interval: 1.640-4.426, P < .001) and prolonged length of stay (beta = 1.045, standard error = 0.159, 95% confidence interval: 0.733-1.357, P < .001). CONCLUSION: Our study showed that small airway dysfunction increased the incidence of postoperative pulmonary complications and prolonged length of stay in patients undergoing thoracoscopic surgery for lung cancer.