Prognostic role of dynamic changes in inflammatory indicators in patients with non-small cell lung cancer treated with immune checkpoint inhibitors-a retrospective cohort study.

Background: Immune checkpoint inhibitors (ICIs) have become one of the standard treatments for non-small cell lung cancer (NSCLC) patients without driver mutations. However, a considerable proportion of patients suffer from severe immune side effects and fail to respond to ICIs. As effective biomarkers, programmed cell death ligand 1 (PD-L1) expression, microsatellite instability (MSI), the tumor mutation burden (TMB) and tumor-infiltrating lymphocytes (TILs) require invasive procedures that place heavy physical and psychological burdens on patients. This study aims to identify simple and effective markers to optimize patient selection through therapeutic decisions and outcome prediction. Methods: This retrospective study comprised 95 patients with metastatic NSCLC who were treated with ICIs either as the standard of care or in a clinical trial. The following data were extracted from the medical records. The baseline and dynamic neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated in the present study. Responses were assessed by computed tomography (CT) imaging and classified according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 every 6-12 weeks during treatment. Results: In total, 95 patients were included in the present study. The median age of patients was 61 years, 83.2% (79/95) patients were male, 62.1% (59/95) were former or current smokers, 66.3% (63/95) had adenocarcinoma, 93.7% (89/95) had stage IV disease, and 87.4% were without molecular alterations. A higher overall response rate (ORR) and prolonged median progression-free survival (PFS) was observed in patients with a lower cycle 3 (C3) NLR [7.7 vs. 5.5 months, hazard ratio (HR): 1.70, 95% confidence interval (CI): 0.90-3.22; P=0.12] and derived NLR (dNLR) (8.2 vs. 5.6 months, HR: 1.67, 95% CI: 0.94-2.97; P=0.08). After two cycles of ICI treatment, patients who had an increased NLR, dNLR, and PLR had a lower ORR and an inferior median PFS than those with a decreased NLR (5.5 vs. 8.5 months, HR: 1.87, 95% CI: 1.09-3.21; P=0.02), dNLR (5.6 vs. 8.4 months, HR: 1.49, 95% CI: 0.87-2.57; P=0.15), and PLR (11.8 vs. 5.5 months, HR: 2.28, 95% CI: 1.32-3.94; P=0.003). Moreover, patients with both an increased NLR and PLR had a worse ORR and median PFS than those with either an increased NLR or PLR, or both an increased NLR and PLR (11.8 vs. 5.5 vs. 5.6 months, P=0.003). In addition, the dynamic changes in the PLR could serve as an independent predictive factor of PFS in NSCLC patients treated with ICIs. Conclusions: Elevated dynamic changes in the NLR and PLR were associated with lower response rates and shorter PFS in the patients with NSCLC treated with ICIs. Our results also highlight the role of dynamic changes in the PLR in identifying patients with NSCLC who could benefit from ICIs.

Enhancing long-segmental tracheal restoration: A self-repairing hydrogel loaded with chondrocytokines for sutureless anastomosis and cartilage regeneration.

Artificial tracheal substitutes encounter significant challenges during long-segmental tracheal defects (LSTD) reconstruction, notably early postoperative anastomotic stenosis and tracheal chondromalacia. Mitigating early anastomotic stenosis by creating a compliant sutureless substitute is pivotal. Enhancing its chondrogenic capacity is equally critical for sustained healthy tracheal cartilage regeneration. This study proposes a self-healing hydrogel for sutureless tracheal anastomosis to mitigate anastomotic stenosis, enriched with kartogenin (KGN) and transforming growth factor-ß1 (TGFß1) to bolster chondrogenic properties. Initially, two precursor solutions were prepared: 1) aldehyde-modified hyaluronic acid with sulfonation and ß-cyclodextrin-CHO loaded with KGN; 2) hydrazide-grafted gelatin loaded with TGFß1. Coextrusion of these solutions resulted in a gelated G + TGFß1/sH-CD + KGN hydrogel, characterized by a robust covalent bonding network of acylhydrazones between hydrazide and aldehyde groups, imparting excellent self-healing properties. The G + TGFß1/sH-CD + KGN hydrogels, showcasing favorable cytocompatibility, excellent injectability, and rapid gelation, were loaded with bone marrow stem cells. These were customized into O-shaped rings and assembled into a malleable tracheal substitute using our established ring-to-tube method. This resultant compliant substitute facilitated sutureless anastomosis of LSTD in a rabbit model, attributed to the Schiff base reaction between the hydrogel's carbonyl group and the tissue's amino group. Notably, the tracheal substitute reduced early postoperative anastomotic stenosis, maintained tracheal patency, alleviated sputum blockage, promoted reepithelization, and increased the survival rate of the experimental rabbits. The sustained release of chondrocytokines resulted in excellent tracheal cartilage regeneration. Employing chondrocytokines-loaded hydrogels with self-healing properties represents a significant advancement in sutureless tracheal anastomosis and tracheal cartilage regeneration, holding promising potential in inhibiting early postoperative anastomotic stenosis and tracheal chondromalacia when treating LSTD.

Electroacupuncture versus solifenacin succinate for female overactive bladder: study protocol for a multicentre, randomised, controlled, double-dummy, non-inferiority trial.

INTRODUCTION: Overactive bladder (OAB) affects approximately 500 million people worldwide, with a higher prevalence in women than in men, significantly impacting the quality of life of female patients. Treatment options for OAB are currently limited. Previous research has proposed that electroacupuncture could be a viable treatment for OAB in women, but there is a lack of high-quality clinical evidence. This study aims to evaluate the effectiveness of electroacupuncture as a safe and efficient non-pharmacological treatment for female OAB by comparing it with solifenacin succinate. METHODS AND ANALYSIS: This study is a multicentre, single-blind, double-dummy randomised controlled non-inferiority clinical trial involving 204 eligible female participants with OAB. Participants will be randomly assigned in a 1:1 ratio to either the electroacupuncture group (receiving electroacupuncture and placebo) or the solifenacin succinate group (receiving sham electroacupuncture and solifenacin succinate). Each participant will undergo 12 sessions of electroacupuncture (or sham electroacupuncture) treatment and solifenacin succinate (or placebo) treatment over a 4-week period. The primary outcome measure will be the percentage change in the number of micturition episodes every 24 hours at week 4 compared with baseline. Secondary outcomes will include a percentage reduction in the number of micturition episodes every 24 hours at 2th, 8th and 16th weeks of the trial, Overactive Bladder Symptom Score, number of urinary incontinence and urgency episodes every 24 hours based on a 3-day voiding diary, OAB Questionnaire, Generalised Anxiety Disorder Scale-7, King's Health Questionnaire and Participant Self-evaluation of Therapeutic Effects. Adverse events will be monitored throughout the study. Efficacy analyses will be conducted on both the intention-to-treat population and the per-protocol set population. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Medical Ethics Committee of Longhua Hospital Shanghai University of Traditional Chinese Medicine (approval number: 2022LCSY097). Each participant will sign a written informed consent before randomisation. The results of this study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER : NCT05798403.

Alginate-based injectable probiotic/squid ink composite hydrogels for accelerated wound healing of MRSA infected abscess through photothermally synergized probiotic therapy.

Methicillin-resistant Staphylococcus aureus (MRSA) infections pose great challenges to skin wound care due to the severe drug resistance developed in the clinic. There is an urgent need to exploit next-generation bactericidal therapeutics that are both antibiotic-free and multifunctional for enhanced wound healing. Herein, we designed a Ca2+-crosslinked alginate hydrogel (EcNSIN@Alg) containing two naturally derived bioactive components, probiotics Escherichia coli Nissle1917 (EcN) and Squid ink nanoparticles (SIN), to treat MRSA-infected wounds. The injectable composite hydrogel displayed excellent biocompatibility, photothermal antibacterial activity, and reactive oxygen species (ROS) scavenging property. Importantly, the probiotic EcN can enhance the photothermal SIN to promote immune regulatory activities, shifting pro-inflammatory macrophages (M1) to anti-inflammatory macrophages (M2). In an MRSA-infected abscess model, EcNSIN@Alg can reduce the expression level of wound inflammatory factors and ROS, increase the number of anti-inflammatory macrophages, accelerate collagen deposition and promote wound healing. This work offers a new perspective on developing safe, antibiotic-free, multifunctional bactericides using fully bioderived materials, with potential applications in clinical practice.

Diagnosis of rare Loffler endocarditis by cardiac ultrasound: a case report and literature review.

Loffler endocarditis is a rare disease associated with high mortality rates, therefore early diagnosis and prompt treatment are crucial factors in managing this condition effectively. The clinical manifestations are nonspecific which can lead to misdiagnosis easily. Here we report a case of rare idiopathic hypereosinophilic syndrome with Loffler endocarditis as the first presentation, first suspected acute coronary syndrome, diagnosed correctly by cardiac ultrasound. The purpose is to improve our understanding of the ultrasound manifestations of this disease.

Caveolin-1 protects retinal ganglion cells in glaucoma by reducing TLR4 and activating the Akt/PTEN signaling pathway.

Glaucoma is a degenerative disease characterized by retinal ganglion cell (RGC) death and visual impairment caused by elevated intraocular pressure (IOP). Elevated IOP can activate microglia, which participate in ganglion cell injury. Based on the study of caveolin-1 (Cav-1) in glaucoma, we aimed to explore the effect and mechanism of Cav-1 on RGC apoptosis in mice with acute ocular hypertension (AOH). AOH mice were established, and Cav-1 was intravitreally injected. Retinal microglia and RGCs were isolated from neonatal mice. TUNEL staining, hematoxylin-eosin staining, immunohistochemistry, flow cytometry, PCR and western blotting were used to observe the effect of Cav-1 on RGCs and mouse retinas. The thickness of the whole retina and the inner retinal sublayer decreased significantly, retinal cell apoptosis increased after AOH injury, and Cav-1 treatment reversed the effect of AOH injury. In addition, Cav-1 treatment promoted the conversion of proinflammatory M1 microglia to anti-inflammatory M2 microglia. Microglia and RGCs were isolated from neonatal mice. Cav-1 protects RGCs from OGD/R-induced injury by changing the polarization status of retinal microglia in vitro. Further studies revealed that Cav-1 activated the Akt/PTEN signaling pathway and inhibited TLR4. Our study provides evidence that Cav-1 may be a promising therapeutic target for glaucoma.

Improving the cycling stability of lithium metal anodes through separator modification with nano-molybdenum powder.

The deposition of lithium ions in an uneven manner can lead to the formation of lithium dendrites, which can puncture the battery separator and cause a short circuit. Additionally, intermediate polysulfides can shuttle between the separator, resulting in damage to the capacity of lithium-sulfur batteries and corrosion of the negative electrode. It is crucial to address these issues promptly. Hence, we developed a modified separator using nano-molybdenum powder, which effectively inhibits the growth of lithium dendrites and suppresses the shuttle effect of polysulfides. The modified separator extends the lifetime of the lithium metal anode, and the uniform pore distribution of the molybdenum powder facilitates the uniform diffusion of Li+ ions, thereby slowing down the detrimental effects. As a result, Li-S cells equipped with the nano-molybdenum powder modified separator achieve a remarkable capacity of 802 mA h g-1 at a current density of 0.5C and maintain a capacity of up to 614 mA h g-1 after 200 cycles.

Engineered bacterial membrane vesicle as safe and efficient nano-heaters to reprogram tumor microenvironment for enhanced immunotherapy.

The immunosuppressive tumor microenvironment (TME) in solid tumors often impedes the efficacy of immunotherapy. Bacterial outer membrane vesicles (OMVs), as a promising cancer vaccine that can potently stimulate immune responses, have garnered interest as a potential platform for cancer therapy. However, the low yield of OMVs limits their utilization. To address this limitation, we developed a novel approach to synthesize OMV-like multifunctional synthetic bacterial vesicles (SBVs) by pretreating bacteria with ampicillin and lysing them through sonication. Compared to OMVs, the yield of SBVs increased by 40 times. Additionally, the unique synthesis process of SBVs allows for the encapsulation of bacterial intracellular contents, endowing SBVs with the capability of delivering catalase (CAT) for tumor hypoxia relief and activating the host cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. To overcome the toxicity of lipopolysaccharide (LPS) on the SBVs surface, we decorated SBVs with a biocompatible polydopamine (PDA) shell, which allowed TME reprogramming using SBVs to be conducted without adverse side effects. Additionally, the photosensitizer indocyanine green (ICG) was loaded into the PDA shell to induce immunogenic cell death and further improve the efficacy of immunotherapy. In summary, the SBVs-based therapeutic platform SBV@PDA/ICG (SBV@P/I) can synergistically elicit safe and potent tumor-specific antitumor responses through combined immunotherapy and phototherapy.

A jasmonate-mediated regulatory network modulates diurnal floret opening time in rice.

Diurnal floret opening time (DFOT) is a pivotal trait for successful fertilization and hybrid breeding in rice. However, the molecular mechanism underlying this trait is poorly understood in rice. In this study, we combined the cytological, genetic and molecular studies to demonstrate that jasmonic acid (JA) regulates DFOT in rice through modulating the turgor and osmotic pressure of the lodicules. We show that lodicules undergo dramatic morphologic changes, accompanied by changes in water and sugar contents during the process of floret opening. Consistently, a large set of genes associated with cell osmolality and cell wall remodeling exhibits distinct expression profiles at different time points in our time-course transcriptomes of lodicules. Notably, a group of JA biosynthesis and signaling genes is continuously upregulated, accompanied by a gradual increase in JA accumulation as floret opening approaching. Furthermore, we demonstrate that the JA biosynthesis gene OsAOS1 is required for endogenous JA biosynthesis in lodicules and promoting rice DFOT. Moreover, OsMYC2, a master regulator of JA signaling, regulates rice DFOT by directly activating OsAOS1, OsSWEET4, OsPIP2;2 and OsXTH9. Collectively, our findings establish a core regulatory network mediated by JA for modulating rice DFOT and provide effective gene targets for the genetic improvement of DFOT in rice.

Zinc oxide nanoparticles intercalated with porous carbon as a separator coating for improving the stability of lithium metal anodes.

Metal lithium negative electrodes are considered the "holy grail" of lithium battery negative electrodes due to their ultra-high energy density and low overpotential. However, the arbitrary growth of lithium dendrites during the cycling process hindered its industrialization process. We prepared porous carbon doped with zinc oxide nanoparticles (ZNC-MOF-5) by high-temperature carbonization of MOF-5, and coated ZNC-MOF-5 on the surface of commercial membranes (ZNC-MOF-5@PP). Used to improve the cycling stability of metal lithium negative electrodes. Zinc oxide nanoparticles in ZNC-MOF-5 have good lithium affinity and can promote Li+ deposition. The porous structure with a high specific surface area endows the electrode with high lithium loading capacity, reduces local current density, and obtains a dendrite-free metal lithium negative electrode. The electrochemical cycling performance of Li/Cu batteries indicates that, ZNC-MOF-5@PP. The separator can prevent the growth of dendrites and improve cycling stability, proving that ZNC-MOF-5 can effectively guide the deposition of Li and solve dendrite problems.

Monitoring of parasite Orobanche cumana using Vis-NIR hyperspectral imaging combining with physio-biochemical parameters on host crop Helianthus annuus.

KEY MESSAGE: This study provided a non-destructive detection method with Vis-NIR hyperspectral imaging combining with physio-biochemical parameters in Helianthus annuus in response to Orobanche cumana infection that took insights into the monitoring of sunflower weed. Sunflower broomrape (Orobanche cumana Wallr.) is an obligate weed that attaches to the host roots of sunflower (Helianthus annuus L.) leading to a significant reduction in yield worldwide. The emergence of O. cumana shoots after its underground life-cycle causes irreversible damage to the crop. In this study, a fast visual, non-invasive and precise method for monitoring changes in spectral characteristics using visible and near-infrared (Vis-NIR) hyperspectral imaging (HSI) was developed. By combining the bands sensitive to antioxidant enzymes (SOD, GR), non-antioxidant enzymes (GSH, GSH + GSSG), MDA, ROS (O2-, OH-), PAL, and PPO activities obtained from the host leaves, we sought to establish an accurate means of assessing these changes and conducted imaging acquisition using hyperspectral cameras from both infested and non-infested sunflower cultivars, followed by physio-biochemical parameters measurement as well as analyzed the expression of defense related genes. Extreme learning machine (ELM) and convolutional neural network (CNN) models using 3-band images were built to classify infected or non-infected plants in three sunflower cultivars, achieving accuracies of 95.83% and 95.83% for the discrimination of infestation as well as 97.92% and 95.83% of varieties, respectively, indicating the potential of multi-spectral imaging systems for early detection of O. cumana in weed management.

Prevalence of childhood hypertension and associated factors in Zhejiang Province: a cross-sectional analysis based on random forest model and logistic regression.

With childhood hypertension emerging as a global public health concern, understanding its associated factors is crucial. This study investigated the prevalence and associated factors of hypertension among Chinese children. This cross-sectional investigation was conducted in Pinghu, Zhejiang province, involving 2,373 children aged 8-14 years from 12 schools. Anthropometric measurements were taken by trained staff. Blood pressure (BP) was measured in three separate occasions, with an interval of at least two weeks. Childhood hypertension was defined as systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) ≥ age-, sex-, and height-specific 95th percentile, across all three visits. A self-administered questionnaire was utilized to collect demographic, socioeconomic, health behavioral, and parental information at the first visit of BP measurement. Random forest (RF) and multivariable logistic regression model were used collectively to identify associated factors. Additionally, population attributable fractions (PAFs) were calculated. The prevalence of childhood hypertension was 5.0% (95% confidence interval [CI]: 4.1-5.9%). Children with body mass index (BMI) ≥ 85th percentile were grouped into abnormal weight, and those with waist circumference (WC) > 90th percentile were sorted into central obesity. Normal weight with central obesity (NWCO, adjusted odds ratio [aOR] = 5.04, 95% CI: 1.96-12.98), abnormal weight with no central obesity (AWNCO, aOR = 4.60, 95% CI: 2.57-8.21), and abnormal weight with central obesity (AWCO, aOR = 9.94, 95% CI: 6.06-16.32) were associated with an increased risk of childhood hypertension. Childhood hypertension was attributable to AWCO mostly (PAF: 0.64, 95% CI: 0.50-0.75), followed by AWNCO (PAF: 0.34, 95% CI: 0.19-0.51), and NWCO (PAF: 0.13, 95% CI: 0.03-0.30). Our results indicated that obesity phenotype is associated with childhood hypertension, and the role of weight management could serve as potential target for intervention.

Fluoroquinolones-related psychiatric adverse events: a real­world retrospective and pharmacovigilance database analysis.

OBJECTIVE: The purpose of this study was to evaluate the pharmacovigilance and clinical characteristics of psychiatric adverse events(AEs) related to Fluoroquinolones(FQs), and to determine the risk factors for timely management. METHODS: Data about AE reporting comes from the FDA Adverse Event Reporting System (FAERS) database, which was used for pharmacovigilance assessments. In addition, we also analyzed the cases of psychiatric AEs related to FQs retrospectively. RESULTS: Both of the FAERS database analysis and literature reports show that the proportion of FQs-related psychiatric AEs reported in females were higher (51.11% VS 33.44% and 53.23% VS 46.77%). Both of them show that the proportion of psychiatric AEs caused by FQs was higher in the age groups of 19-44 (28.08% and 40.32%) and 45-64 (28.17% and 25.81%). Most psychiatric AEs occurred within 10 days after FQs administration. Literature shows that 67.74% of the psychiatric AEs disappeared within 3 days after drug withdrawal (some cases were accompanied by other drug). CONCLUSION: Psychiatric AEs caused by FQs are serious, and there are many important safety signals that have not been mentioned in the label or previous studies. It is very important to identify and manage psychiatric AEs in time for the safe use of FQs.

PGD 2 /DP1 axis promotes liver regeneration by secreting Wnt2 in KCs in mice.

BACKGROUND AND AIMS: The liver possesses a remarkable regenerative capacity in response to injuries or viral infections. Various growth factors and cytokines are involved in regulating liver regeneration. Prostaglandin D 2 , a pro-resolution lipid mediator, is the most abundant hepatic prostanoid. However, the role of prostaglandin D 2 in the injury-induced liver regeneration remains unclear. APPROACH AND RESULTS: Two-thirds partial hepatectomy (70% PH), massive hepatectomy (85% resection), and carbon tetrachloride-induced chronic injury were performed in mice to study the mechanisms of live regeneration. Hepatic prostaglandin D 2 production was elevated in mice after PH. Global deletion of D prostanoid receptor (DP) 1, but not DP2, slowed PH-induced liver regeneration in mice, as evidenced by lower liver weight to body weight ratio, less Ki67 + hepatocyte proliferation, and G2/M phase hepatocytes. In addition, DP1 deficiency, specifically in resident KCs, and not in endothelial cells or HSCs, retarded liver regeneration in mice after PH. Conversely, the overexpression of exogenous DP1 in KCs accelerated liver regeneration in mice. Mechanistically, DP1 activation promoted Wnt2 transcription in a PKA/CREB-dependent manner in resident KCs and mediated hepatocyte proliferation through Frizzled8/ß-catenin signaling. Adeno-associated virus vector serotype 8-mediated Frizzled8 knockdown in hepatocytes attenuated accelerated liver regeneration in KC-DP1 transgenic mice after PH. Treatment with the DP1 receptor agonist BW245C promotes PH-induced liver regeneration in mice. CONCLUSIONS: DP1 activation mediates crosstalk between KCs and hepatocytes through Wnt2 and facilitates liver regeneration. Hence, DP1 may serve as a novel therapeutic target in acute and chronic liver diseases.

Weiwei Decoction alleviates gastric intestinal metaplasia through the olfactomedin 4/nucleotide-binding oligomerization domain 1/caudal-type homeobox gene 2 signaling pathway.

BACKGROUND: Gastric intestinal metaplasia (IM) is a precancerous lesion that is associated with an elevated risk of gastric carcinogenesis. Weiwei Decoction (WWD) is a promising traditional Chinese herbal formula widely employed in clinical for treating IM. Previous studies suggested the potential involvement of the olfactomedin 4 (OLFM4)/nucleotide-binding oligomerization domain 1 (NOD1)/caudal-type homeobox gene 2 (CDX2) signaling pathway in IM regulation. AIM: To verify the regulation of the OLFM4/NOD1/CDX2 pathway in IM, specifically investigating WWD's effectiveness on IM through this pathway. METHODS: Immunohistochemistry for OLFM4, NOD1, and CDX2 was conducted on tissue microarray. GES-1 cells treated with chenodeoxycholic acid were utilized as IM cell models. OLFM4 short hairpin RNA (shRNA), NOD1 shRNA, and OLFM4 pcDNA were transfected to clarify the pathway regulatory relationships. Protein interactions were validated by co-immunoprecipitation. To explore WWD's pharmacological actions, IM rat models were induced using N-methyl-N'-nitro-N-nitrosoguanidine followed by WWD gavage. Gastric cells were treated with WWD-medicated serum. Cytokines and chemokines content were assessed by enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction. RESULTS: The OLFM4/NOD1/CDX2 axis was a characteristic of IM. OLFM4 exhibited direct binding and subsequent down-regulation of NOD1, thereby sustaining the activation of CDX2 and promoting the progression of IM. WWD improved gastric mucosal histological lesions while suppressing intestinal markers KLF transcription factor 4, villin 1, and MUCIN 2 expression in IM rats. Regarding pharmacological actions, WWD suppressed OLFM4 and restored NOD1 expression, consequently reducing CDX2 at the mRNA and protein levels in IM rats. Parallel regulatory mechanisms were observed at the protein level in IM cells treated with WWD-medicated serum. Furthermore, WWD-medicated serum treatment strengthened OLFM4 and NOD1 interaction. In case of anti-inflammatory, WWD restrained interleukin (IL)-6, interferon-gamma, IL-17, macrophage chemoattractant protein-1, macrophage inflammatory protein 1 alpha content in IM rat serum. WWD-medicated serum inhibited tumor necrosis factor alpha, IL-6, IL-8 transcriptions in IM cells. CONCLUSION: The OLFM4/NOD1/CDX2 pathway is involved in the regulation of IM. WWD exerts its therapeutic efficacy on IM through the pathway, additionally attenuating the inflammatory response.

Reactive astrogliosis induced by TNF-α is associated with upregulated AEG-1 together with activated NF-κB pathway in vitro.

Astrocyte-elevated gene-1 (AEG-1/MTDH/LYRIC) has garnered signficant attention in cancer research, yet, its role in inflammation-associated astrogliosis remains underexplored. This study aims to elucidate the effects of AEG-1 on reactive astrogliosis, including proliferation, migration, and glutamate uptake in primary astrocytes derived from rats. We first confirmed the effect of AEG-1 on these parameters. Subsequently, we investigated whether AEG-1 plays a role in the process of pro-inflammation factors such as tumor necrosis factor-alpha (TNF-α) induced astrogliosis. Our findings revealed that AEG-1-lentivirus infection led to hypertrophic cell bodies and enhanced expression of astrogliosis markers, including glial fibrillary acidic protein (GFAP) and vimentin. Additionally, AEG-1 was found to upregulate the mRNA and protein expression levels of EAAT2, a major glutamate transporter in the brain predominantly expressed by astrocytes and responsible for 90% of glutamate clearance. Furthermore, TNF-α was shown to promote astrogliosis, as well as astrocyte proliferation and migration, by upregulating AEG-1 expression through the NF-κB pathway. Collectively, these results suggest a potential role for AEG-1 in inflammation-related astrogliosis.

Partial response to trastuzumab deruxtecan (DS8201) following progression in HER2-amplified breast cancer with pulmonary metastases managed with disitamab vedotin (RC48): a comprehensive case report and literature review.

Breast cancer remains one of the predominant malignancies worldwide. In the context of inoperable advanced or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer, systemic management primarily relies on HER2-targeting monoclonal antibodies. With the successful development of anti-HER2 antibody-drug conjugates (ADCs), these agents have been increasingly integrated into therapeutic regimens for metastatic breast cancer. Here, we present the case of a 42-year-old female patient with HER2-positive pulmonary metastatic breast cancer who underwent an extensive treatment protocol. This protocol included chemotherapy, radiation therapy, hormonal therapy, surgical intervention on the breast, and anti-HER2 therapies. The anti-HER2 therapies involved both singular and dual targeting strategies using trastuzumab and the ADC disitamab vedotin (RC48) over an 8-year period. After experiencing disease progression following HER2-targeted therapy with RC48, the patient achieved noticeable partial remission through a therapeutic regimen that combined trastuzumab deruxtecan (DS8201) and tislelizumab. The data suggest a promising role for DS8201 in managing advanced stages of HER2-amplified metastatic breast cancer, especially in cases that demonstrate progression after initial HER2-directed therapies using ADCs. Furthermore, its combination with anti-PD-1 agents enhances therapeutic efficacy by augmenting the anti-tumoral immune response.

Exploring the prognostic analysis of autophagy and tumor microenvironment based on monocyte cells in lung cancer.

A deep understanding of the biological mechanisms of lung cancer offers more precise treatment options for patients. In our study, we integrated data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) to investigate lung adenocarcinoma. Analyzing 538 lung cancer samples and 31 normal samples, we focused on 3076 autophagy-related genes. Using Seurat, dplyr, tidyverse, and ggplot2, we conducted single-cell data analysis, assessing the quality and performing Principal Component Analysis (PCA) and t-SNE analyses. Differential analysis of TCGA data using the "Limma" package, followed by immune infiltration analysis using the CIBERSORT algorithm, led us to identify seven key genes. These genes underwent further scrutiny through consensus clustering and gene set variation analysis (GSVA). We developed a prognostic model using Lasso Cox regression and multivariable Cox analysis, which was then validated with a nomogram, predicting survival rates for lung adenocarcinoma. The model's accuracy and universality were corroborated by ROC curves. Additionally, we explored the relationship between immune checkpoint genes and immune cell infiltration and identified two key genes, HLA-DQB1 and OLR1. This highlighted their potential as therapeutic targets. Our comprehensive approach sheds light on the molecular landscape of lung adenocarcinoma and offers insights into potential treatment strategies, emphasizing the importance of integrating single-cell and genomic data in cancer research.

Comparative Transcriptome Analysis of T. rubrum, T. mentagrophytes, and M. gypseum Dermatophyte Biofilms in Response to Photodynamic Therapy.

Dermatophyte biofilms frequently count for inadequate responses and resistance to standard antifungal treatments, resulting in refractory chronic onychomycosis infection. Although antimicrobial photodynamic therapy (aPDT) has clinically proven to exert significant antifungal effects or even capable of eradicating dermatophyte biofilms, considerably less is known about the molecular mechanisms underlying aPDT and the potential dysregulation of signaling networks that could antagonize its action. The aim of this study is to elucidate the molecular mechanisms underlining aPDT combat against dermatophyte biofilm in recalcitrant onychomycosis and to decipher the potential detoxification processes elicited by aPDT, facilitating the development of more effective photodynamic interventions. We applied genome-wide comparative transcriptome analysis to investigate how aPDT disrupting onychomycosis biofilm formed by three distinct dermatophytes, including Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum gypseum, the most frequently occurring pathogenic species. In total, 352.13 Gb of clean data were obtained for the transcriptomes of dermatophyte biofilms with or without aPDT treatment, resulting in 2,422.42 million reads with GC content of 51.84%, covering 99.9%, 98.5% and 99.4% of annotated genes of T. rubrum, T. mentagrophytes, and M. gypseum, respectively. The genome-wide orthologous analysis identified 6624 transcribed single-copy orthologous genes in all three species, and 36.5%, 6.8% and 17.9% of which were differentially expressed following aPDT treatment. Integrative orthology analysis demonstrated the upregulation of oxidoreductase activities is a highly conserved detoxification signaling alteration in response to aPDT across all investigated dermatophyte biofilms. This study provided new insights into the molecular mechanisms underneath anti-dermatophyte biofilm effects of aPDT and successfully identified a conserved detoxification regulation upon the aPDT application.