Unveiling heterogeneity and prognostic markers in ductal breast cancer through single-cell RNA-seq.

BACKGROUND: Breast cancer (BC) is a heterogeneous disease, with the ductal subtype exhibiting significant cellular diversity that influences prognosis and response to treatment. Single-cell RNA sequencing data from the GEO database were utilized in this study to investigate the underlying mechanisms of cellular heterogeneity and to identify potential prognostic markers and therapeutic targets. METHODS: Bioinformatics analysis was conducted using R packages to analyze the single-cell sequencing data. The presence of highly variable genes and differences in malignant potency within the same BC samples were examined. Differential gene expression and biological function between Type 1 and Type 2 ductal epithelial cells were identified. Lasso regression and Cox proportional hazards regression analyses were employed to identify genes associated with patient prognosis. Experimental validation was performed in vitro and in vivo to confirm the functional relevance of the identified genes. RESULTS: The analysis revealed notable heterogeneity among BC cells, with the presence of highly variable genes and differences in malignant behavior within the same samples. Significant disparities in gene expression and biological function were identified between Type 1 and Type 2 ductal epithelial cells. Through regression analyses, CYP24A1 and TFPI2 were identified as pivotal genes associated with patient prognosis. Kaplan-Meier curves demonstrated their prognostic significance, and experimental validation confirmed their inhibitory effects on malignant behaviors of ductal BC cells. CONCLUSION: This study highlights the cellular heterogeneity in ductal subtype breast cancer and delineates the differential gene expressions and biological functions between Type 1 and Type 2 ductal epithelial cells. The genes CYP24A1 and TFPI2 emerged as promising prognostic markers and therapeutic targets, exhibiting inhibitory effects on BC cell malignancy in vitro and in vivo. These findings offer the potential for improved BC management and the development of targeted treatment strategies.

Prediction of cerebral infarction after bypass surgery in adult moyamoya disease: using pulsatility index on TCD.

BACKGROUND: At present, the most effective treatment for symptomatic moyamoya disease (MMD) is surgery. However, the high incidence of postoperative complications is a serious problem plaguing the surgical treatment of MMD, especially the acute cerebral infarction. Decreased cerebrovascular reserve is an independent risk factor for ischemic infarction, and the pulsatility index (PI) of transcranial Doppler (TCD) is a common intuitive index for evaluating intracranial vascular compliance. However, the relationship between PI and the occurrence of ischemic stroke after operation is unclear. OBJECTIVE: To explore whether the PI in the middle cerebral artery (MCA) could serve as a potential predictor for the occurrence of ischemic infarction after bypass surgery in MMD. METHODS: We performed a retrospective analysis of data from 71 patients who underwent combined revascularization surgery, including superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis and encephalo-duro-myo-synangiosis (EDMS). The patients were divided into two groups according to the median of ipsilateral MCA-PI before operation, low PI group (MCA-PI < 0.614) and high PI group (MCA-PI ≥ 0.614). Univariate and multivariate regression analysis were used to explore risk factors affecting the occurrence of postoperative cerebral infarction. RESULTS: Among the 71 patients with moyamoya disease, 11 patients had cerebral infarction within one week after revascularization. Among them, 10 patients' ipsilateral MCA-PI were less than 0.614, and another one's MCA- PI is higher than 0.614. Univariate analysis showed that the lower ipsilateral MCA-PI (0.448 ± 0.109 vs. 0.637 ± 0.124; P = 0.001) and higher Suzuki stage (P = 0.025) were linked to postoperative cerebral infarction. Multivariate analysis revealed that lower ipsilateral MCA-PI was an independent risk factor for predicting postoperative cerebral infarction (adjusted OR = 14.063; 95% CI = 6.265 ~ 37.308; P = 0.009). CONCLUSIONS: A lower PI in the ipsilateral MCA may predict the cerebral infarction after combined revascularization surgery with high specificity. And combined revascularization appears to be safer for the moyamoya patients in early stages.

Mechanism of scutellarin inhibition of astrocyte activation to type A1 after ischemic stroke.

OBJECTIVE: The aim of this study was to investigate the effects of scutellarin on the activation of astrocytes into the A1 type following cerebral ischemia and to explore the underlying mechanism. METHODS: In vivo, a mouse middle cerebral artery wire embolism model was established to observe the regulation of astrocyte activation to A1 type by scutellarin, and the effects on neurological function and brain infarct volume. In vitro, primary astrocytes were cultured to establish an oxygen-glucose deprivation model, and the mRNA and protein expression of C3, a specific marker of A1-type astrocytes pretreated with scutellarin, were examined. The neurons were cultured in vitro to detect the toxic effects of ischemia-hypoxia-activated A1 astrocyte secretion products on neurons, and to observe whether scutellarin could reduce the neurotoxicity of A1 astrocytes. To validate the signaling pathway-related proteins regulated by scutellarin on C3 expression in astrocytes. RESULTS: The results showed that scutellarin treatment reduced the volume of cerebral infarcts and attenuated neurological deficits in mice caused by middle cerebral artery embolism. Immunofluorescence and Western blot showed that treatment with scutellarin down-regulated middle cerebral artery embolism and OGD/R up-regulated A1-type astrocyte marker C3. The secretory products of ischemia-hypoxia-activated A1-type astrocytes were toxic to neurons and induced an increase in neuronal apoptosis, and astrocytes treated with scutellarin reduced the toxic effects on neurons. Further study revealed that scutellarin inhibited the activation of NF-κB signaling pathway and thus inhibited the activation of astrocytes to A1 type.

FN1 mediated activation of aspartate metabolism promotes the progression of triple-negative and luminal a breast cancer.

BACKGROUND: Breast cancer (BC) is regarded as one of the most common cancers diagnosed among the female population and has an extremely high mortality rate. It is known that Fibronectin 1 (FN1) drives the occurrence and development of a variety of cancers through metabolic reprogramming. Aspartic acid is considered to be an important substrate for nucleotide synthesis. However, the regulatory mechanism between FN1 and aspartate metabolism is currently unclear. METHODS: We used RNA sequencing (RNA seq) and liquid chromatography-mass spectrometry to analyze the tumor tissues and paracancerous tissues of patients. MCF7 and MDA-MB-231 cells were used to explore the effects of FN1-regulated aspartic acid metabolism on cell survival, invasion, migration and tumor growth. We used PCR, Western blot, immunocytochemistry and immunofluorescence techniques to study it. RESULTS: We found that FN1 was highly expressed in tumor tissues, especially in Lumina A and TNBC subtypes, and was associated with poor prognosis. In vivo and in vitro experiments showed that silencing FN1 inhibits the activation of the YAP1/Hippo pathway by enhancing YAP1 phosphorylation, down-regulates SLC1A3-mediated aspartate uptake and utilization by tumor cells, inhibits BC cell proliferation, invasion and migration, and promotes apoptosis. In addition, inhibition of FN1 combined with the YAP1 inhibitor or SLC1A3 inhibitor can effectively inhibit tumor growth, of which inhibition of FN1 combined with the YAP1 inhibitor is more effective. CONCLUSION: Targeting the "FN1/YAP1/SLC1A3/Aspartate metabolism" regulatory axis provides a new target for BC diagnosis and treatment. This study also revealed that intratumoral metabolic heterogeneity plays an important role in the progression of different subtypes of breast cancer.

Risk factors for target vessel endoleaks after physician-modified fenestrated or branched endovascular aortic repair for postdissection thoracoabdominal aortic aneurysms.

OBJECTIVE: Patients with postdissection thoracoabdominal aortic aneurysms (TAAAs) have been more likely to develop endoleaks than those with degenerative TAAAs after fenestrated or branched endovascular aortic repair (F/BEVAR). In the present study, we aimed to determine the risk factors for target vessel (TV)-related endoleaks after visceral segment F/BEVAR for postdissection TAAAs. METHODS: We performed a retrospective analysis of all patients with degenerative and postdissection TAAAs treated with F/BEVAR between 2017 and 2021. All the patients had undergone computed tomography angiography before and 3 months, 6 months, and annually after discharge. Two experienced vascular surgeons had used data from computed tomography angiography and vascular angiography to judge the presence of endoleaks. The study end points were mortality, aneurysm rupture, and the emergence of and reintervention for TV-related endoleaks. RESULTS: A total of 195 patients (mean age, 66 ± 10 years; 69% men) had undergone F/BEVAR for 99 postdissection TAAAs and 96 degenerative TAAAs. During a mean follow-up of 16 ± 12 months, we found that the patients with postdissection TAAAs were younger (age, 64 ± 10 years vs 69 ± 9 years; P = .001), had required more prior aortic repairs (58% vs 40%; P = .012), and had had a higher body mass index (26.1 ± 3.4 kg/m2 vs 24.8 ± 3 kg/m2; P = .008), a larger visceral segment aortic diameter (47.1 ± 7.5 mm vs 44.5 ± 7.5 mm; P = .016), and more TV-related endoleaks (18% vs 7%; P = .023) compared with those with degenerative TAAAs. Of the 99 patients with postdissection TAAAs, 327 renal-mesenteric arteries were revascularized using 12 scallops, 141 fenestrations, and 174 inner or outer branch stents. A total of 25 TV-related endoleaks were identified among 18 patients during follow-up, including 6 type Ic (retrograde from the distal end of the branch), 3 type IIIb (bridging stent fabric tear), and 16 type IIIc endoleaks (detachment or loose connection of the bridging stent). The patients with an endoleak had had a larger visceral aortic diameter (52.7 ± 6.4 mm vs 45.8 ± 7.2 mm; P < .001) and had undergone revascularization of more TVs (3.7 ± 0.7 vs 3.2 ± 0.9; P = .032). In contrast, true lumen compression did not seem to affect the occurrence of TV endoleaks (39% vs 27%; P = .323). The use of presewn branch stents in the fenestration position was associated with a lower risk of TV-related endoleaks (5% vs 11%; P = .025). In addition, TVs derived entirely or partially from the false lumen were more prone to the development of endoleaks after reconstruction (19% vs 4% [P < .001]; and 15% vs 4% [P = .047], respectively). CONCLUSIONS: We found that patients with postdissection TAAAs were more likely to have TV-related endoleaks after F/BEVAR in the visceral region than those with degenerative TAAAs. Additionally, patients with a larger aortic diameter and a greater number of fenestrations in the visceral region were more likely to have experienced TV-related endoleaks. Branch vessels deriving from the false lumen were also more likely to develop endoleaks after reconstruction, and prefabricated branch stents were related to a lower possibility of TV-related endoleaks.

Narrower-band multiplet resonances of surface plasmons on periodically phase-shifted metal gratings.

In this Letter, we report properties of surface plasmon resonances (SPRs) on metal gratings with periodic phase shifts, in which high-order SPR modes corresponding to the long-pitch (a few to tens of wavelengths, λ) phase shifts are excited, instead of those corresponding to the short-pitch (∼λ) gratings. In particular, it is shown that, for quarter-phase shifts, spectral features of doublet SPR modes with narrower bandwidths are notably present when the underlying first-order short-pitch SPR mode is designed to be located between an arbitrarily chosen pair of neighboring high-order long-pitch SPR modes. Also, the positions and interspacing of the doublet SPR modes can be arbitrarily tuned by adjusting the pitch values. Resonance characteristics of this phenomenon are numerically investigated, and an analytical formulation based on coupled-wave theory is developed to elucidate the resonance conditions. Characteristics of the narrower-band doublet SPR modes may find application in the resonant control of light-matter interactions involving photons of multiple frequencies, and in high-precision SPR sensing with multi-probing channels.

Identification of Genes Associated with Prognosis and Immunotherapy Prediction in Triple-Negative Breast Cancer via M1/M2 Macrophage Ratio.

Background and Objectives: Triple-negative breast cancer (TNBC), a highly aggressive and heterogeneous subtype of breast cancer, accounts for ap-proximately 10-15% of all breast cancer cases. Currently, there is no effective therapeutic target for TNBC. Tu-mor-associated macrophages (TAMs), which can be phenotypically classified into M1 and M2 subtypes, have been shown to influence the prognosis of various cancers, including ovarian cancer. This study aimed to investigate the role of M1/M2 macrophages in the TNBC tumor microenvironment (TME), with a focus on identifying prognostic genes and predicting immunotherapy response. Materials and Methods: The study employed the CIBERSORT algorithm to analyze immune cell expression in the TME. Genes associated with the M1/M2 macrophage ratio were identified using Pearson correlation analysis and used to classify patients into dis-tinct clusters. Dimensionality reduction techniques, including univariate Cox regression and Lasso, were applied to these genes. The expression of prognostic genes was validated through immunohistochemistry. Results: The study found a high prevalence of TAMs in the TME. Among the patient clusters, 109 differentially expressed genes (DEGs) were identified. Three significant DEGs (LAMP3, GZMB, and CXCL13) were used to construct the riskScores. The riskScore model effectively stratified patients based on mortality risk. Gene Set Enrichment Analysis (GSEA) associated the riskScore with several significant pathways, including mismatch repair, JAK/STAT3 signaling, VEGF signaling, antigen processing presentation, ERBB signaling, and P53 signaling. The study also predicted patient sensitivity to im-munotherapy using the riskScores. The expression of the three significant DEGs was validated through immunohisto-chemistry. Conclusions: The study concluded that the riskScore model, based on the M1/M2 macrophage ratio, is a valid prognostic tool for TNBC. The findings underscore the importance of the TME in TNBC progression and prognosis and highlight the po-tential of the riskScore model in predicting immunotherapy response in TNBC patients.

Downregulated PEG3 ameliorates cardiac fibrosis and myocardial injury in mice with ischemia/reperfusion through the NF-κB signaling pathway.

Expression of paternally-expressed gene 3 (PEG3) has been identified in new cardiac adult stem cell population, which is involved in post-myocardial infarction remodeling. The cardiac fibroblasts function in the repair and remodeling events after myocardial ischemia, while the role of PEG3 in these events has not been investigated yet. In this study, artificial knockdown of PEG3 through p-LV-GFP-sh-PEG3 injection was performed in a ischemia/reperfusion (I/R) mouse model to explore the role of PEG3 in cardiac fibrosis, myocardial injury and cardiomyocyte apoptosis. Besides, the involvement of nuclear factor kappa B (NF-κB) pathway was illuminated by transduction of inhibitor pyrrolidine dithiocarbamate (PDTC). Both shRNA-mediated silencing of PEG3 and inhibition of the NF-κB signaling pathway were shown to significantly reduce myocardial injury, infarction size, alleviated myocardium remodeling and cardiac fibrosis, along with repressed cardiomyocyte apoptosis. Additionally, we also found that the NF-κB signaling pathway activation was blocked by PEG3 silencing, which could further enhance the protective effects of PEG3 inhibition against I/R induced injury. This study highlights the importance of PEG3 silencing in preventing cardiac fibrosis and myocardial injury after I/R by inactivating the NF-κB signaling pathway.

Over-expression of CDX2 alleviates breast cancer by up-regulating microRNA let-7b and inhibiting COL11A1 expression.

BACKGROUND: microRNA Let-7 serves as a tumor suppressor by targeting various oncogenic pathways in cancer cells. However, the underlying mechanism of its involvement in breast cancer remains largely unknown. With our research, our endeavor is to explore the role of the CDX2/let-7b/COL11A1 axis in breast cancer cell activities. METHODS: Tumor tissues and adjacent normal tissues were collected from 86 patients with breast cancer. Human breast cancer epithelial cell line MCF-7 was treated with over-expressed CDX2, let-7b mimic, shRNA against COL11A1 and their negative controls. The expression of CDX2, let-7b, and COL11A1 in the tissues and cells was determined by RT-qPCR. Interactions among CDX2, let-7b, and COL11A1 were detected by ChIP and dual-luciferase reporter assay, respectively. After different transfections, cell invasion, migration, and proliferation abilities were determined by Transwell and EdU assays. Lastly, tumor xenografts in nude mice were established and hematoxylin and eosin staining was performed to assess the tumor growth and lymph node metastasis. RESULTS: CDX2 and let-7b were poorly expressed in breast cancer cells and tissues. CDX2 bound to let-7b and promoted the expression of let-7b, which contrarily inhibited the expression of COL11A1. Cancer cell proliferation, invasion, migration, and metastasis were stimulated when CDX2 and let-7b were depleted or COL11A1 was over-expressed. Xenograft tumors growth and metastasis were in accordance with the results of cellular experiments. CONCLUSION: In agreement with these observations, we could reach a conclusion that CDX2 could promote let-7b expression, which may exert an inhibitory effect on the proliferation, migration, and metastasis of breast cancer cells via repressing the expression of COL11A1, providing a novel therapeutic strategy for the treatment of metastatic breast cancer.

A translational bioinformatic approach in identifying and validating an interaction between Vitamin A and CYP19A1.

INTRODUCTION: One major challenge in personalized medicine research is to identify the environmental factors that can alter drug response, and to investigate their molecular mechanisms. These environmental factors include co-medications, food, and nutrition or dietary supplements. The increasing use of dietary supplements and their potential interactions with cytochrome P450 (CYP450) enzymes is a highly significant personalized medicine research domain, because most of the drugs on the market are metabolized through CYP450 enzymes. METHODS: Initial bioinformatics analysis revealed a number of regulators of CYP450 enzymes from a human liver bank gene expression quantitative loci data set. Then, a compound-gene network was constructed from the curated literature data. This network consisted of compounds that interact with either CYPs and/or their regulators that influence either their gene expression or activity. We further evaluated this finding in three different cell lines: JEG3, HeLa, and LNCaP cells. RESULTS: From a total of 868 interactions we were able to identify an interesting interaction between retinoic acid (i.e. Vitamin A) and the aromatase gene (i.e. CYP19A1). Our experimental results showed that retinoic acid at physiological concentration significantly influenced CYP19A1 gene expressions. CONCLUSIONS: These results suggest that the presence of retinoic acid may alter the efficacy of agents used to suppress aromatase expression.

Nasal inhalation of butorphanol in combination with ketamine quickly elevates the mechanical pain threshold in the model of chronic constriction injury to the sciatic nerve of rat.

BACKGROUND: The aim of the present study is to explore the impact of butorphanol in combination with ketamine via nasal inhalation (NI) on neuropathic pain induced by chronic constriction injury (CCI) to the sciatic nerve in a rat model. METHODS: CCI rats (n = 12) were equally randomized to four groups based on the treatments received as follows: 100 µL of 0.9% normal saline via NI (NS/NI group); 100 µg of butorphanol plus 1 mg of ketamine via NI (B + K/NI group); 100 µg of butorphanol alone via NI (B/NI group); and 100 µg of butorphanol plus 1 mg of ketamine via subcutaneous injection (B + K/SC group). Mechanical pain threshold was measured at 10 min, 30 min, 2 h, 4 h, and 6 h after drug administration. RESULTS: The mechanical pain threshold in the B + K/NI group was improved significantly 4 h after drug administration as compared with that in the B/NI or B + K/SC group (P < 0.05). The onset and intensity of drug action in the B + K/NI group were better than those of the other two groups, but the duration of drug action was not prolonged. CONCLUSIONS: NI of butorphanol in combination with ketamine quickly elevates the mechanical pain threshold in a rat neuropathic pain model induced by CCI to the sciatic nerve.

[Effectiveness of sequential method pure single-port lumpectomy-breast conserving surgery for early-stage breast cancer in different quadrants].

Objective: To compare the effectiveness of sequential method pure single-port lumpectomy-breast conserving surgery (SMPSL-BCS) in treating early-stage breast cancer patients with tumors in different quadrants. Methods: A retrospective analysis was conducted on 200 early-stage breast cancer female patients admitted between January 2023 and December 2023. According to the quadrant where the tumor was located, the patients were allocated into the upper outer quadrant group (UO group), lower outer quadrant group (LO group), upper inner quadrant group (UI group), and lower inner quadrant group (LI group), with 50 cases in each group. There was no significant difference ( P>0.05) in the baseline data, including age, body mass index, smoking history, marital status, comorbidities, affected breast side, maximum tumor diameter on ultrasound, maximum pathological tumor diameter, clinical tumor stage, molecular subtype, and disease duration. The operation time, intraoperative blood loss, postoperative drainage volume, and extubation time were recorded and compared between groups. Additionally, the occurrence of early-stage complications (1-3 months after operation; including subcutaneous fluid accumulation, incision infection, superficial skin burns) and late-stage complications (>3 months after operation; including pectoralis major muscle adhesion, changes in breast appearance and shape, sensory discomfort) were assessed. At 6 months after operation, the cosmetic outcome of breast-conserving surgery was rated for all groups. Results: The UO group had the shortest operation time, followed by the UI group, LO group, and LI group, showing significant differences between groups ( P<0.05). The UO group had the least intraoperative blood loss, followed by the LO group, UI group, and LI group; except for the difference between UO group and LO group, which was not significant ( P>0.05), the differences between the other groups were significant ( P<0.05). The UO group had the least postoperative drainage volume, followed by the LO group, UI group, and LI group; except for the difference between LO group and UI group, which was not significant ( P>0.05), the differences between the other groups were significant ( P<0.05). The extubation time of the LI group was significantly longer than that of the other groups ( P<0.05). All patients were followed up 4-12 months, with an average of 8 months. And 193 patients were followed up more than 6 months, including 48 patients in UO group, 47 in LO group, 49 in UI group, and 49 in LI group. In the early-stage period, the LI group had a higher incidence of subcutaneous fluid accumulation after tube removal compared to the UO group and LO group ( P<0.05), while there was no significant difference in the incidences of other early complications between groups ( P>0.05). In the late-stage period, the LI group had significantly higher incidences of pectoralis major muscle adhesion and changes in breast appearance and shape than UO group and LO group ( P<0.05), and a significantly higher incidence of sensory discomfort than UO group ( P<0.05). There was no significant difference in the incidences of other late-stage complications between groups ( P>0.05). At 6 months after operation, the cosmetic outcomes of breast-conserving surgery were significantly better in UO group, LO group, and UI group than in LI group ( P<0.05); there was no significant difference between the other groups ( P>0.05). Conclusion: In the treatment of early-stage breast cancer using SMPSL-BCS, patients with tumors located in the upper outer quadrant show the best effectiveness. The effectivenesses are similar for patients with tumors in the lower outer and upper inner quadrants. However, patients with tumors in the lower inner quadrant do not experience significant advantages. Therefore, it is recommended that SMPSL-BCS should not be the first-choice surgical method for patients with tumors in the lower inner quadrant.

CX3CR1 mediates motor dysfunction in mice through 5-HTR2a.

CX3CR1 knockout could induce motor dysfunction in several neurological disease models mainly through regulating microglia's function. While CX3CR1 was expressed on neurons in a few reports, whether neuronal CX3CR1 could affect the function of neurons and mediate motor dysfunction under physiological conditions is unknown. To elucidate the roles of neuronal CX3CR1 on motor dysfunction, CX3CR1 knockout mice were created. Rotarod test and Open field test found that the CX3CR1-/- mice's motor capacity was reduced. Immunofluorescence staining detected the expression of CX3CR1 in neurons both in vivo and in vitro. Immunohistochemistry and West blot found that knockout of CX3CR1 did not affect the neurons' number in both spinal cord and brain of mice. While inhibiting the function of CX3CR1 by AZD8797 could decrease the expression of 5-Hydroxytryptamine receptor(5-HTR2a), which involved in the regulation of motor function. Further investigation revealed that CX3CR1 regulated the expression of HTR2a through the NF-κB pathway. For the first time, we reported that neuronal CXCR1 mediates motor dysfunction. Our results suggest that modulating CXCR1 activity offers a novel therapeutic strategy for motor dysfunction.

Analysis of Fungal Diversity, Physicochemical Properties and Volatile Organic Compounds of Strong-Flavor Daqu from Seven Different Areas.

Strong-flavor Daqu, as a fermentation agent, plays a significant role in shaping the quality of strong-flavor baijius, and fungal species in Daqu are important factors affecting the quality of Daqu. Therefore, we selected strong-flavor Daqu from seven different origins to study the fungal composition and the effects of the fungal composition on the physicochemical properties and volatile organic compounds (VOCs). It was found that the fungal composition influences the physicochemical properties of Daqu. Specifically, there was a positive link between Rhizomucor, Rhizopus, Thermomyces, and liquefying activity and a positive correlation between Aspergillus and fermenting activity. Furthermore, the relationships between esterifying activity and Thermomyces, Rhizomucor, Aspergillus, Pichia, and Saccharomycopsis were found to be positive. The VOCs in Daqu were affected by Aspergillus, Issatchenkia, Pichia, and Thermoascus. Issatchenkia was significantly positively correlated with benzeneethanol as well as Aspergillus and pentadecanoic acid ethyl ester, ethyl myristate. Pichia and Thermoascus were significantly negatively correlated with benzaldehyde and 2-furaldehyde. This study deepens our understanding of the relationship between VOCs, the physicochemical properties with microbial communities, and reference significance for the production of better-quality strong-flavor Daqu.

Mechanisms of Postischemic Stroke Angiogenesis: A Multifaceted Approach.

Ischemic stroke constitutes a significant global health care challenge, and a comprehensive understanding of its recovery mechanisms is imperative for the development of innovative therapeutic strategies. Angiogenesis, a pivotal element of ischemic tissue repair, facilitates the restoration of blood flow to damaged regions, thereby promoting neuronal regeneration and functional recovery. Nevertheless, the mechanisms underlying postischemic stroke angiogenesis remain incompletely elucidated. This review meticulously examines the constituents of the neurovascular unit, ion channels, molecular mediators, and signaling pathways implicated in angiogenesis following stroke. Furthermore, it delves into prospective therapeutic strategies informed by these factors. Our objective is to provide detailed and exhaustive information on the intricate mechanisms governing postischemic stroke angiogenesis, thus providing a robust scientific foundation for the advancement of novel neurorepair therapies.

Toremifene, an Alternative Adjuvant Endocrine Therapy, Is Better Than Tamoxifen in Breast Cancer Patients with CYP2D6*10 Mutant Genotypes.

PURPOSE: Tamoxifen showed individual differences in efficacy under different CYP2D6*10 genotypes. Our study evaluated the prognosis of tamoxifen or toremifene in hormone receptor (HR)-positive breast cancer patients under different genotypes. MATERIALS AND METHODS: CYP2D6*10 genotypes of HR-positive breast cancer patients were determined by Sanger sequencing, and all the patients were divided into tamoxifen group or toremifene group. RESULTS: A total of 268 patients with HR-positive breast cancer were studied. The median follow-up time was 72.0 months (range, 5.0 to 88.0 months). Of these, 88 (32.9%), 114 (42.5%), and 66 (24.6%) patients had C/C, C/T, and T/T genotypes, respectively. Among patients who received tamoxifen (n=176), the 5-year disease-free survival (DFS) rate in patients with C/C and C/T genotype was better than that in patients with T/T genotype, and the difference was statistically significant (p < 0.001 and p=0.030, respectively). In patients receiving toremifene, CYP2D6*10 genotype was not significantly associated with DFS (p=0.325). Regardless of genotypes, the 5-year DFS rate was higher in patients treated with toremifene than in patients with tamoxifen (91.3% vs. 80.0%, p=0.011). Compared with tamoxifen, toremifene remained an independent prognostic marker of DFS in multivariate analysis (hazard ratio, 0.422; p=0.021). For all the 180 patients with CYP2D6*10 C/T and T/T genotypes, the 5-year DFS rate was significantly higher in the toremifene group than in the tamoxifen group (90.8% vs. 70.1%, p=0.003). CONCLUSION: Toremifene may be an alternative adjuvant endocrine therapy for patients with CYP2D6*10 mutant genotypes.

Lactiplantibacillus plantarum A72, a Strain with Antioxidant Properties, Obtained through ARTP Mutagenesis, Affects Caenorhabditis elegans Anti-Aging.

This research endeavored to elucidate the antioxidant attributes of lactic acid bacteria, specifically their impact on anti-aging and lifespan augmentation in Caenorhabditis elegans. The study focused on Lactiplantibacillus plantarum A72, identified through ARTP mutagenesis for its potent antioxidant properties. In vitro analysis affirmed its free radical neutralizing capacity. In C. elegans, the strain not only extended the lifespan by 25.13% and amplified motility 2.52-fold, but also maintained reproductive capabilities. Remarkably, Lpb. plantarum A72 diminished reactive oxygen species (ROS) and malondialdehyde (MDA) levels in C. elegans by 34.86% and 69.52%, respectively, while concurrently enhancing its antioxidant enzyme activities. The strain also bolstered C. elegans survival rates by 46.33% and 57.78% under high temperature and H2O2 conditions, respectively. Transcriptomic scrutiny revealed that Lpb. plantarum A72 could retard C. elegans aging and extend lifespan by upregulating the sod-5 and hsp-16.1 genes and downregulating the fat-6 and lips-17 genes. These findings propose Lpb. plantarum A72 as a potential antioxidant and anti-aging lactic acid bacteria.

Expression of MAC30 protein is related to survival and clinicopathological variables in breast cancer.

BACKGROUND AND OBJECTIVES: MAC30 is a protein with unknown function that is differentially expressed in certain malignancies. The aims of this study were to evaluate the relationship between MAC30 expression and clinicopathologic features while investigate the prognostic value of MAC30 expression in breast cancer. METHODS: Immunohistochemistry was used to examine MAC30 expression in 243 breast cancer tissues, meanwhile in 59 matched adjacent noncancerous tissues and 46 benign breast tumor tissues as controls. The correlation of MAC30 expression with clinicopathological parameters was assessed using χ(2) analysis. The Kaplan-Meier method and Cox proportional hazards model were used to predict factors with a significant independent prognostic value. RESULTS: MAC30 was overexpressed in breast cancer compared with matched adjacent noncancerous tissues and benign breast tumor (both P < 0.001). Moreover, MAC30 expression was correlated with tumor size, TNM stage, lymph node metastasis, and recurrence. Furthermore, it was shown that patients with high MAC30 expression had significantly poorer overall survival (OS) and disease-free survival (DFS; P = 0.002 and P = 0.007, respectively). Multivariate Cox regression analysis revealed that high MAC30 expression was an independent prognostic factor for both OS and DFS (P = 0.018 and P = 0.044, respectively). CONCLUSIONS: Overexpression of MAC30 was associated with tumor progression, recurrence, and poor survival in breast cancer. Testing expression of MAC30 will be helpful for predicting prognosis in breast cancer.

Chemical Composition and Flavor Characteristics of Cider Fermented with Saccharomyces cerevisiae and Non-Saccharomyces cerevisiae.

Cider flavor has a very important impact on the quality. Solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) combined with gas chromatography-ion mobility spectrometry (GC-IMS) tested different kinds of non-Saccharomyces yeasts and Saccharomyces cerevisiae (S. cerevisiae) co-inoculated for the fermentation of cider to determine differences in aroma material, and the determination of odor activity value (OAV) is applied less frequently in research. Through Rhodotorula mucilaginosa, Debaryomyces hansenii, Zygosaccharomyces bailii, and Kluyveromyces Marxianus, four different strains of non-Saccharomyces yeast fermented cider, and it was found that, in both the chemical composition and flavor of material things, compared with monoculture-fermented cider using S. cerevisiae, all differences were significant. Co-inoculated fermentation significantly improved the flavor and taste of cider. As in the volatile compounds of OVA > 1, octanoic acid (Sc 633.88 µg/L, co-inoculation fermented group 955.49 µg/L) provides vegetable cheese fragrance and decanoic acid, ethyl ester (Sc 683.19 µg/L, co-inoculation fermented group 694.98 µg/L) a creamy fruity fragrance, etc., and the average content increased after co-inoculated fermentation. Phenylethyl alcohol, which can produce a rose scent, was relatively abundant in cider samples and varied greatly among the groups. Moreover, the contents of ethyl lactate and 1-butanol in the Sc+Rm (ciders fermented by S. cerevisiae and R. mucilaginosa) were the highest of all of the cider samples. Different types of non-Saccharomyces yeast produced cider with different flavor characteristics. This study demonstrates that different species of non-Saccharomyces yeast do have an important impact on the characteristics of cider and that co-inoculation with non-Saccharomyces yeast and S. cerevisiae for cider fermentation may be a strategy to improve the flavor of cider.