Novel Electrolytic Regeneration Method for Cyclic Regeneration of Ozone Decomposition MnOx Catalysts.

The deactivation of ozone decomposition catalysts has been a bottleneck in their industrial application. As an efficient catalyst regeneration method, the liquid-phase method has attracted wide attention due to its operability and universality. However, the amount of waste liquid generated by the used regeneration liquid is a major drawback of its application. Therefore, we propose an electrolytic regeneration method for cyclic regeneration of MnOx ozone decomposition catalysts by combining the advantages of the electrolytic process. In this method, NaNO2 solution is used to react with O22- to efficiently regenerate the inactivated MnOx catalysts, while NO2- is oxidized to NO3-, and then the oxidized NO3- can be efficiently reduced to NO2- through the electrolysis process at the cathode with an 88% Faraday efficiency, ultimately realizing the recycling of the NO2-/NO3- regeneration solution. By this method, the regeneration of inactivated MnOx ozone catalysts can be realized only using electricity.

Exosomal miR-486 derived from bone marrow mesenchymal stem cells promotes angiogenesis following cerebral ischemic injury by regulating the PTEN/Akt pathway.

Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) have been shown to promote angiogenesis after ischemic stroke, in which microRNAs (miRs) are believed to play an important role in exosome-mediated therapeutic effects, though the mechanism is still not clear. In this study, a series of molecular biological and cellular assays, both in vitro and in vivo, were performed to elucidate the role of exosomal miR-486 in angiogenesis following cerebral ischemic and its molecular mechanisms. Our results revealed that BMSC-Exos significantly improved neurological function and increased microvessel density in ischemic stroke rats. In vitro assays showed that BMSC-Exos promoted the proliferation, migration, and tube formation ability of oxygen-glucose deprivation/reoxygenation (OGD/R) injured rat brain microvascular endothelial cells (RBMECs). Importantly, BMSC-Exos increased the expression of miR-486 and phosphorylated protein kinase B (p-Akt) and down-regulated the protein level of phosphatase and tensin homolog (PTEN) in vivo and in vitro. Mechanistic studies demonstrated that transfection with miR-486 mimic enhanced RBMECs angiogenesis and increased p-Akt expression, while inhibited PTEN expression. On the other hand, the miR-486 inhibitor induced an opposite effect, which could be blocked by PTEN siRNA. It was thus concluded that exosomal miR-486 from BMSCs may enhance the functional recovery by promoting angiogenesis following cerebral ischemic injury, which might be related to its regulation of the PTEN/Akt pathway.

Ubiquitination plays an important role during the formation of chicken primordial germ cells.

As an important post-translational modification, ubiquitination plays an important role in regulating protein homeostasis in eukaryotic cells. In our previous studies, both the transcriptome and proteome suggested that ubiquitination is involved in the formation of chicken primordial germ cells (PGCs). Here, affinity enrichment combined with liquid chromatography (LC)-tandem mass spectrometry (MS/MS) was used to analyze the ubiquitome during the differentiation from embryonic stem cells (ESCs) to PGCs, and we identify that 724 lysine ubiquitinated sites were up-regulated in 558 proteins and 138 lysine ubiquitinated sites were down-regulated in 109 proteins. Furthermore, GO and KEGG enrichment analysis showed that ubiquitination regulates key proteins to participate in the progression of key events related to PGC formation and the transduction of key signals such as Wnt, MAPK and Insulin signals, followed by the detailed explanation of the specific regulatory mechanism of ubiquitination through the combined proteome and ubiquitome analysis. Moreover, both the activation and inhibition of neddylation were detrimental to the maintenance of the biological characteristics of PGCs, which also verified the importance of ubiquitination. In conclusion, this study provides a global view of the ubiquitome during the formation of PGCs by label-free quantitative ubiquitomics, which lays a theoretical foundation for the formation mechanism and specific application of chicken PGCs.

Analysis of the Molecular Mechanism of Energy Metabolism in the Sex Differentiation of Chickens Based on Transcriptome Sequencing.

The determination of sex in mammals is established and controlled by various complex mechanisms. In contrast, sex control in poultry remains an unresolved issue. In this study, RNA-sequencing was conducted for male gonads and ovarian tissues in chicken embryos of up to 18.5 days to identify metabolic factors influencing male and female sex differentiation, as well as gonadal development. Our results reveal that PKM2, a critical glycolysis-related protein, plays a significant role in chicken sex differentiation via PPARG, a crucial hormone gene. We propose that our discoveries bolster the notion that glycolysis and oxidative phosphorylation function as antecedent contributors to sexual phenotypic development and preservation.

Outcome Comparison in Hospitalized COVID-19 Patients With and Without AKI.

Aim: Patients hospitalized with COVID-19 have a higher incidence of Acute Kidney Injury (AKI) compared with non-COVID patients. Previous observational studies showed AKI in hospitalized patients with COVID-19 was associated with significant increased mortality rate. We conducted a retrospective cohort study in a large mid-Atlantic health system to investigate whether COVID-19 associated AKI during hospitalization would lead to worse outcomes in a predominant Black patient population, compared to COVID-19 without AKI. Methods: We reviewed health records of patients (aged≥18 years) admitted with symptomatic COVID-19 between March 5, 2020, and Jun 3, 2020, in 9 acute care facilities within the MedStar Health system. Patients were followed up until 3 months after discharge. Primary outcome was inpatient mortality. Secondary outcomes were need for ICU level of care, need for intubation, length of ICU stay, length of hospital stay, need for renal replacement therapy, recovery of renal function. Results: Among 1107 patients admitted with symptomatic COVID-19, the AKI incidence rate was 35 %. African American patients made up 63 % of the total patient population and 74 % of the total AKI population. Inpatient mortality in the AKI group and the non-AKI group was 163 (41.9 %) and 71 (9.9 %), respectively. COVID-19 patients with AKI had significant higher risk of in-patient mortality (OR, 4.71 [95 % CI, 3.38-6.62], P < 0.001), ICU admission (OR, 4.27 [95 % CI, 3.21-5.72], P < 0.001) and need of intubation (OR, 6.18 [95 % CI, 4.45-8.68], P < 0.001). Conclusions: AKI in hospitalized patients with COVID-19 was associated with higher mortality rate, need for intubation and ICU admission compared to COVID-19 patients without AKI group.

Postoperative EEG abnormalities in relation to neurodevelopmental outcomes after pediatric cardiac surgery.

BACKGROUND: We had reported that postoperative EEG background including sleep-wake cycle (SWC) and discharge (seizures, spikes/sharp waves) abnormalities were significantly correlated with adverse early outcomes in children after cardiac surgery. We aimed to analyze the relations between these EEG abnormalities and neurodevelopmental outcomes at about 2 years after cardiac surgery. METHODS: We enrolled 121 patients undergoing cardiac surgery at 3.3 months (0.03 ~ 28 months). EEG abnormalities described above during the first postoperative 48 h were evaluated. Griffiths Mental Development Scales-Chinese was used to evaluate the quotients of overall development and 5 subscales of the child's locomotor, language, personal-social, eye-hand coordination and performance skills at 16 ~ 31 months of age. RESULTS: EEG background abnormalities occurred in 59/121 (48.8%) patients and 33 (55.9%) unrecovered to normal by 48 h. Abnormal SWC occurred in 15 (12.4%) patients and 7 (5.8%) unrecovered to normal by 48 h. EEG seizures occurred in 11 (9.1%) patients with frontal lobe seizures in 4. Spikes/sharp waves occurred in 100 (82.6%). EEG background abnormalities, number of spikes/sharp waves and frontal lobe seizures were significantly associated with neurodevelopmental impairment at about 1 ~ 2 year after surgery (Ps ≤ 0.05). CONCLUSIONS: Most parameters of EEG abnormalities were significantly associated with neurodevelopmental impairment after cardiac surgery. IMPACT: Neurodevelopmental impairment in children with congenital heart disease remain poorly understood. Previous studies had reported that either EEG seizures or background abnormalities were associated with worse neurodevelopmental outcomes. Our present study showed that all the EEG background and discharge abnormalities including EEG background, seizures and spikes/sharp waves in the early postoperative period were significantly associated with neurodevelopmental impairment at about 1 ~ 2 years after cardiac surgery. Comprehensive evaluation of early postoperative EEG may provide further insights about postoperative brain injury, its relation with neurodevelopmental impairment, and guide to improve clinical management.

Therapeutic Strategies for Ischemic Stroke: Modulating the Adult Neural Stem Cell Niche through the Wnt/ß-catenin Pathway.

Stroke is a prominent contributor to mortality and impairment on a global scale. Ischemic stroke accounts for approximately 80% of stroke cases and is caused by occlusion of cerebral blood vessels. Enhancing neurogenesis through the modulation of the neural stem cell niche in the adult brain is a promising therapeutic strategy for individuals afflicted with ischemic stroke. Neurogenesis results in the generation of newborn neurons that serve as replacements for deceased neural cells within the ischemic core, thereby playing a significant role in the process of neural restoration subsequent to cerebral ischemia. Research has shown that activation of the Wnt/ß-catenin pathway can augment neurogenesis following cerebral ischemia, suggesting that this pathway is a potentially beneficial therapeutic target for managing ischemic stroke. This review provides an extensive analysis of the current knowledge regarding the involvement of the Wnt/ß-catenin pathway in promoting neurogenesis, thereby offering a promising avenue for therapeutic intervention in the context of ischemic stroke or other neurological impairments.

DDX5 Can Act as a Transcription Factor Participating in the Formation of Chicken PGCs by Targeting BMP4.

As an RNA binding protein (RBP), DDX5 is widely involved in the regulation of various biological activities. While recent studies have confirmed that DDX5 can act as a transcriptional cofactor that is involved in the formation of gametes, few studies have investigated whether DDX5 can be used as a transcription factor to regulate the formation of primordial germ cells (PGCs). In this study, we found that DDX5 was significantly up-regulated during chicken PGC formation. Under different PGC induction models, the overexpression of DDX5 not only up-regulates PGC markers but also significantly improves the formation efficiency of primordial germ cell-like cells (PGCLC). Conversely, the inhibition of DDX5 expression can significantly inhibit both the expression of PGC markers and PGCLC formation efficiency. The effect of DDX5 on PGC formation in vivo was consistent with that seen in vitro. Interestingly, DDX5 not only participates in the formation of PGCs but also positively regulates their migration and proliferation. In the process of studying the mechanism by which DDX5 regulates PGC formation, we found that DDX5 acts as a transcription factor to bind to the promoter region of BMP4-a key gene for PGC formation-and activates the expression of BMP4. In summary, we confirm that DDX5 can act as a positive transcription factor to regulate the formation of PGCs in chickens. The obtained results not only enhance our understanding of the way in which DDX5 regulates the development of germ cells but also provide a new target for systematically optimizing the culture and induction system of PGCs in chickens in vitro.

Effect of cooking methods on volatile compounds and texture properties in maize porridge.

To investigate the optimal processing of maize porridge, the volatile compounds and texture under different cooking methods and time have been studied. A total of 51 volatile compounds were identified in maize porridge. Notably, the major volatiles, aldehydes and esters exhibited a relatively high content in electric pressure cooker (EPC), and esters tend to significantly increase after cooking. Among aldehydes, nonanal and hexanal played a great role in flavor due to their relatively high content. Volatile compounds of maize porridge in different cooking methods could be clearly distinguished by multiple chemometrics. Furthermore, texture analysis revealed that almost all the indicators in the EPC can reach the lowest value at 60 min. To summarize, different cooking methods had a more significant influence on the volatile compounds and texture compared to time. This study helps to improve the sensory attributes of maize porridge, and thus contributes to healthier and more sustainable production.

CD3, CD8, IFN-γ, tumor and stroma inflammatory cells as prognostic indicators for surgically resected SCLC: evidences from a 10-year retrospective study and immunohistochemical analysis.

Current clinical guidelines limit surgical intervention to patients with cT1-2N0M0 small cell lung cancer (SCLC). Our objective was to reassess the role of surgery in SCLC management, and explore novel prognostic indicators for surgically resected SCLC. We reviewed all patients diagnosed with SCLC from January 2011 to April 2021 in our institution. Survival analysis was conducted using the Kaplan-Meier method, and independent prognostic factors were assessed through the Cox proportional hazard model. In addition, immunohistochemistry (IHC) staining was performed to evaluate the predictive value of selected indicators in the prognosis of surgically resected SCLC patients. In the study, 177 SCLC patients undergoing surgical resection were ultimately included. Both univariate and multivariate Cox analysis revealed that incomplete postoperative adjuvant therapy emerged as an independent risk factor for adverse prognosis (p < 0.001, HR 2.96). Survival analysis revealed significantly superior survival among pN0-1 patients compared to pN2 patients (p < 0.0001). No significant difference in postoperative survival was observed between pN1 and pN0 patients (p = 0.062). Patients with postoperative stable disease (SD) exhibited lower levels of tumor inflammatory cells (TIC) (p = 0.0047) and IFN-γ expression in both area and intensity (p < 0.0001 and 0.0091, respectively) compared to those with postoperative progressive disease (PD). Conversely, patients with postoperative SD showed elevated levels of stromal inflammatory cells (SIC) (p = 0.0453) and increased counts of CD3+ and CD8+ cells (p = 0.0262 and 0.0330, respectively). Survival analysis indicated that high levels of SIC, along with low levels of IFN-γ+ cell area within tumor tissue, may correlate positively with improved prognosis in surgically resected SCLC (p = 0.017 and 0.012, respectively). In conclusion, the present study revealed that the patients with pT1-2N1M0 staging were a potential subgroup of SCLC patients who may benefit from surgery. Complete postoperative adjuvant therapy remains an independent factor promoting a better prognosis for SCLC patients undergoing surgical resection. Moreover, CD3, CD8, IFN-γ, TIC, and SIC may serve as potential indicators for predicting the prognosis of surgically resected SCLC.

The Effect of Inhibiting the Wingless/Integrated (WNT) Signaling Pathway on the Early Embryonic Disc Cell Culture in Chickens.

The utilization of chicken embryonic-derived pluripotent stem cell (PSC) lines is crucial in various fields, including growth and development, vaccine and protein production, and germplasm resource protection. However, the research foundation for chicken PSCs is relatively weak, and there are still challenges in establishing a stable and efficient PSC culture system. Therefore, this study aims to investigate the effects of the FGF2/ERK and WNT/ß-catenin signaling pathways, as well as different feeder layers, on the derivation and maintenance of chicken embryonic-derived PSCs. The results of this study demonstrate that the use of STO cells as feeder layers, along with the addition of FGF2, IWR-1, and XAV-939 (FIX), allows for the efficient derivation of chicken PSC-like cells. Under the FIX culture conditions, chicken PSCs express key pluripotency genes, such as POUV, SOX2, and NANOG, as well as specific proteins SSEA-1, C-KIT, and SOX2, indicating their pluripotent nature. Additionally, the embryoid body experiment confirms that these PSC-like cells can differentiate into cells of three germ layers in vitro, highlighting their potential for multilineage differentiation. Furthermore, this study reveals that chicken Eyal-Giladi and Kochav stage X blastodermal cells express genes related to the primed state of PSCs, and the FIX culture system established in this research maintains the expression of these genes in vitro. These findings contribute significantly to the understanding and optimization of chicken PSC culture conditions and provide a foundation for further exploration of the biomedical research and biotechnological applications of chicken PSCs.

Visual analysis of the research frontiers, hotspots and trends of exercise therapy intervention in tumor-related sleep-wake disorders.

Objective: To systematically understand the research frontiers, hotspots and development trends of exercise therapy in the intervention of tumor-related sleep-wake disorders, and to provide scientific basis for follow-up research. Methods: Downloaded the original research papers on February 26, 2024, from the Web of Science core collection database, on tumor-associated sleep-wake disorders. The data that met the inclusion criteria were imported into the Bibliometric Analysis Platform (http://biblimetric.com), CiteSpace 6.3.R1 and VOSviwer1.6.20 software for visual analysis, and imported into Excel2021. Scientometric analysis was performed with Oringin2021 and PyCharm Community Edition 2022.1.3. Results: A total of 512 original research papers on tumor-related sleep-wake disorders were obtained. The most influential countries in the subject area are the United States, Spain and German, the institutions are the University of California System, Sun Yat Sen University and Northwestern University, et al., the authors are Berger AM, Aaronson NK, Bower JE, et al., and the journals are Cancer, Brit J Cancer and Cancer Nurs. The co-cited references suggest that the current research frontier in the field mainly involves the level, place and program of exercise therapy, including the relationship between physical activity, sedentary behavior and cancer prevention and control. The results of co-occurrence keyword network analysis showed that quality of life, physical activity, breast cancer, exercise, fatigue, and survivors may be the research hotspots in this field, with breast cancer, health, aerobic exercise, adults, and chemotherapy being the most popular. Conclusions: The number of papers published and the research enthusiasm in this field show a steady upward trend. However, there is a lack of influential institutions and scholars, and there is relatively little research collaboration across countries/regions/institutions. The scientific research influence of institutions and scholars in most European and American countries/regions is significantly ahead of that of institutions and scholars in Asian and African countries/regions. But Sun Yat Sen University in China is a relatively active and influential scientific research institution in recent years, which is worthy of attention. In addition, the research frontier of this discipline is the level, place and program of exercise therapy auxiliary intervention, and the research hotspots involve breast cancer, health, aerobic exercise, adults, chemotherapy, et al. Their clinical efficacy needs to be further demonstrated in multi-center, large-sample and high-quality prospective studies.

[Correlation between clinical phenotypes and genotypes among 46 children with SCN1A-related developmental epileptic encephalopathy].

OBJECTIVE: To explore the correlation between clinical phenotypes and genotypes among 46 children with SCN1A-related developmental epileptic encephalopathy (DEE). METHODS: Clinical data of 46 children with DEE and SCN1A variants identified at the Guangzhou Women and Children's Medical Center between January 2018 and June 2022 were collected. The children were grouped based on their age of onset, clinical manifestations, neurodevelopmental status, and results of genetic testing. The correlation between SCN1A genotypes and clinical phenotypes was analyzed. RESULTS: Among the 46 patients, 2 children (4.35%) had developed the symptoms before 3 months of age, 42 (91.30%) were between 3 to 9 months, and 2 cases (4.35%) were after 10 months. Two cases (4.35%) presented with epilepsy of infancy with migrating focal seizures (EIMFS), while 44 (95.7%) had presented with Dravet syndrome (DS), including 28 cases (63.6%) with focal onset (DS-F), 13 cases (29.5%) with myoclonic type (DS-M), 1 case (2.27%) with generalized type (DS-G), and 2 cases (4.55%) with status epilepticus type (DS-SE). Both of the two EIMFS children had severe developmental delay, and among the DS patients, 7 cases had normal development, while the remaining had developmental delay. A total of 44 variants were identified through genetic sequencing, which included 16 missense variants and 28 truncating variants. All EIMFS children had carried the c.677C>T (p.Thr226Met) missense variant. In the DS group, there was a significant difference in the age of onset between the missense variants group and the truncating variants group (P < 0.05). Missense variants were more common in D1 (7/15, 46.7%) and pore regions (8/15, 53.3%), while truncating variants were more common in D1 (12/28, 42.9%). Children with variants outside the pore region were more likely to develop myoclonic seizures. CONCLUSION: The clinical phenotypes of DEE are diverse. There is a difference in the age of onset between individuals with truncating and missense variants in the SCN1A gene. Missense variants outside the pore region are associated with a higher incidence of myoclonic seizures.

Autophagy plays a pro-apoptotic role in arsenic trioxide-induced cell death of liver cancer.

OBJECTIVE: The effects of arsenic trioxide (As2O3) on hepatocellular carcinoma have been documented widely. Autophagy plays dual roles in the survival and death of cancer cells. Therefore, we investigated the exact role of autophagy in As2O3-induced apoptosis in liver cancer cells. METHODS: The viability of hepatoma cells was determined using the MTT assay with or without fetal bovine serum. The rate of apoptosis in liver cancer cells treated with As2O3 was evaluated using flow cytometry, Hoechst 33258 staining, and TUNEL assays. The rate of autophagy among liver cancer cells treated with As2O3 was detected using immunofluorescence, Western blot assay and transmission electron microscopy. RESULTS: Upon treatment with As2O3, the viability of HepG2 and SMMC-7721 cells was decreased in a time- and dose-dependent manner. The apoptosis rates of both liver cancer cell lines increased with the concentration of As2O3, as shown by flow cytometry. Apoptosis in liver cancer cells treated with As2O3 was also shown by the activation of the caspase cascade and the regulation of Bcl-2/Bax expression. Furthermore, As2O3 treatment induced autophagy in liver cancer cells; this finding was supported by Western blot, immunofluorescence of LC3-II and beclin 1, and transmission electron microscopy. In liver cancer cells, As2O3 inhibited the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signal pathway that plays a vital role in both apoptosis and autophagy. The PI3K activator SC-79 partially reversed As2O3-induced autophagy and apoptosis. Furthermore, inhibiting autophagy with 3-methyladenine partially reversed the negative effects of As2O3 on cell viability. Serum starvation increased autophagy and amplified the effect of As2O3 on cell death. CONCLUSION: As2O3 induces apoptosis and autophagy in liver cancer cells. Autophagy induced by As2O3 may have a proapoptotic effect that helps to reduce the viability of liver cancer cells. This study provides novel insights into the effects of As2O3 against liver cancer. Please cite this article as: Deng ZT, Liang SF, Huang GK, Wang YQ, Tu XY, Zhang YN, Li S, Liu T, Cheng BB. Autophagy plays a pro-apoptotic role in arsenic trioxide-induced cell death of liver cancer. J Integr Med. 2024; 22(3): 295-302.

Discovery of a botanical compound as a broad-spectrum inhibitor against gut microbial ß-glucuronidases from the Tibetan medicine Rhodiola crenulata.

Gut microbial ß-glucuronidases (gmß-GUS) played crucial roles in regulating a variety of endogenous substances and xenobiotics on the circulating level, thus had been recognized as key modulators of drug toxicity and human diseases. Inhibition or inactivation of gmß-GUS enzymes has become a promising therapeutic strategy to alleviate drug-induced intestinal toxicity. Herein, the Rhodiola crenulata extract (RCE) was found with potent and broad-spectrum inhibition on multiple gmß-GUS enzymes. Subsequently, the anti-gmß-GUS activities of the major constituents in RCE were tested and the results showed that 1,2,3,4,6-penta-O-galloyl-ß-d-glucopyranose (PGG) acted as a strong and broad-spectrum inhibitor on multiple gmß-GUS (including EcGUS, CpGUS, SaGUS, and EeGUS). Inhibition kinetic assays demonstrated that PGG effectively inhibited four gmß-GUS in a non-competitive manner, with the Ki values ranging from 0.12 µM to 1.29 µM. Docking simulations showed that PGG could tightly bound to the non-catalytic sites of various gmß-GUS, mainly via hydrogen bonding and aromatic interactions. It was also found that PGG could strongly inhibit the total gmß-GUS activity in mice feces, with the IC50 value of 1.24 µM. Collectively, our findings revealed that RCE and its constituent PGG could strongly inhibit multiple gmß-GUS enzymes, suggesting that RCE and PGG could be used for alleviating gmß-GUS associated enterotoxicity.

Enhanced photosynthetic efficiency by nitrogen-doped carbon dots via plastoquinone-involved electron transfer in apple.

Artificially enhancing photosynthesis is critical for improving crop yields and fruit qualities. Nanomaterials have demonstrated great potential to enhance photosynthetic efficiency; however, the mechanisms underlying their effects are poorly understood. This study revealed that the electron transfer pathway participated in nitrogen-doped carbon dots (N-CDs)-induced photosynthetic efficiency enhancement (24.29%), resulting in the improvements of apple fruit qualities (soluble sugar content: 11.43%) in the orchard. We also found that N-CDs alleviated mterf5 mutant-modulated photosystem II (PSII) defects, but not psa3 mutant-modulated photosystem I (PSI) defects, suggesting that the N-CDs-targeting sites were located between PSII and PSI. Measurements of chlorophyll fluorescence parameters suggested that plastoquinone (PQ), the mobile electron carrier in the photosynthesis electron transfer chain (PETC), was the photosynthesis component that N-CDs targeted. In vitro experiments demonstrated that plastoquinone-9 (PQ-9) could accept electrons from light-excited N-CDs to produce the reduced plastoquinone 9 (PQH2-9). These findings suggested that N-CDs, as electron donors, offer a PQ-9-involved complement of PETC to improve photosynthesis and thereby fruit quality. Our study uncovered a mechanism by which nanomaterials enhanced plant photosynthesis and provided some insights that will be useful in the design of efficient nanomaterials for agricultural/horticultural applications.

Hyperactivation of ß-catenin signal in hepatocellular carcinoma recruits myeloid-derived suppressor cells through PF4-CXCR3 axis.

The high mutation rate of CTNNB1 (37 %) and Wnt-ß-catenin signal-associated genes (54 %) has been notified in hepatocellular carcinoma (HCC). The activation of Wnt-ß-catenin signal pathway was reported to be associated with an immune "desert" phenotype, but the underlying mechanism remains unclear. Here we mainly employed orthotopic HCC models to explore on it. Mass cytometry depicted the immune contexture of orthotopic HCC syngeneic grafts, unveiling that the exogenous expression of ß-catenin significantly increased the percentage of myeloid-derived suppressor cells (MDSCs) and decreased the percentage of CD8+ T-cells. Flow cytometry and immunohistochemistry further confirmed the findings. The protein microarray analysis, Western blot and PCR identified PF4 as its downstream regulating cytokine. Intratumorally injection of cytokine PF4 enhanced the accumulation of MDSCs. Knockout of PF4 abolished the effect of ß-catenin on recruiting MDSCs. Chromatin immunoprecipitation and luciferase reporter assay demonstrated that ß-catenin increases the mRNA level of PF4 via binding to PF4's promoter region. In vitro chemotaxis assay and in vivo administration of specific inhibitors identified CXCR3 on MDSCs as receptor for recruiting PF4. Lastly, the significant correlations across ß-catenin, PF4 and MDSCs and CD8+ T-cells infiltration were verified in HCC clinical samples. Our results unveiled HCC tumor cell intrinsic hyperactivation of ß-catenin can recruit MDSC through PF4-CXCR3, which contributes to the formation of immune "desert" phenotype. Our study provided new insights into the development of immunotherapeutic strategy of HCC with CTNNB1 mutation. SIGNIFICANCE: This study identifies PF4-CXCR3-MDSCs as a downstream mechanism underlying CTNNB1 mutation associated immune "desert" phenotype.

The Establishment and Optimization of a Chicken Primordial Germ Cell Induction Model Using Small-Molecule Compounds.

In recent years, inducing pluripotent stem cells to differentiate into functional primordial germ cells (PGCs) in vitro has become an important method of obtaining a large number of PGCs. However, the instability and low induction efficiency of the in vitro PGC induction system restrict the application of PGCs in transgenic animal production, germplasm resource conservation and other fields. In this study, we successfully established a two-step induction model of chicken PGCs in vitro, which significantly improved the formation efficiency of PGC-like cells (PGCLCs). To further improve the PGC formation efficiency in vitro, 5025 differentially expressed genes (DEGs) were obtained between embryonic stem cells (ESCs) and PGCs through RNA-seq. GO and KEGG enrichment analysis revealed that signaling pathways such as BMP4, Wnt and Notch were significantly activated during PGC formation, similar to other species. In addition, we noted that cAMP was activated during PGC formation, while MAPK was suppressed. Based on the results of our analysis, we found that the PGC formation efficiency was significantly improved after activating Wnt and inhibiting MAPK, and was lower than after activating cAMP. To sum up, in this study, we successfully established a two-step induction model of chicken PGCs in vitro with high PGC formation efficiency, which lays a theoretical foundation for further demonstrating the regulatory mechanism of PGCs and realizing their specific applications.

Risk and prognosis of second cutaneous melanoma after radiotherapy for breast cancer: A population-based analysis.

Radiation therapy (RT), a primary treatment for breast cancer (BC), may be associated with increased non-BC tumor risk. We aimed to examine second cutaneous melanoma (SCM) risk in BC patients who underwent RT and to assess their survival outcomes. Data from 520,977 BC patients diagnosed between 1973-2018 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Cumulative SCM incidence was estimated using the Fine-Gray competing risk model. Poisson regression analysis was conducted to calculate the standardized incidence ratio (SIR) and estimate the SCM relative risk in patients who underwent RT compared to those who did not. Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan‒Meier method. Among the 520,977 BC patients, 243,676 (46.8%) underwent surgery and RT, while 277,301 (53.2%) only underwent surgery. Our results suggest that BC patients receiving RT had a higher SCM risk than those who did not (hazard ratio [HR] 1.40; 95% confidence interval [CI] 1.30-1.51; P < 0.001). SCM incidence was also higher in BC patients treated with RT than in the general US population (SIR 1.12; 95% CI 1.05-1.19; P < 0.05). However, SCM patients who received RT had a significantly higher 10-year survival rate than those who did not receive RT (14.90% vs 5.94%; P < 0.001). No significant difference was found in 10-year OS or 5-year CSS between SCM following RT and only primary cutaneous melanoma (OPCM), but SCM patients who did not receive RT had a significantly lower 10-year OS, with no significant difference in CSS. This study suggests an increased SCM likelihood in BC patients due to RT, although the overall risk is minimal.

Comparative study of the vascular structures of the retina and choroid in Chinese Han and Uygur populations with proliferative diabetic retinopathy: An OCTA study.

BACKGROUND: To compare the vascular structures of the retina and choroid in Chinese Han and Uygur populations with proliferative diabetic retinopathy (PDR) using swept-source OCTA (SS-OCTA). METHODS: Fifty-three eyes of 53 healthy volunteers (25 from Hans and 28 from Uygurs) and 40 eyes of 40 PDR patients (20 from Hans and 20 from Uygurs) were included. Retinal and choroidal parameters, including thickness, vessel flow density (VFD), foveal avascular zone (FAZ) area, choroidal vascularity volume and index (CVV and CVI) were evaluated. RESULTS: Compared with the respective controls, superficial capillary plexus (SCP)-VFD and deep capillary plexus (DCP)-VFD, the areas of FAZ in SCP and DCP were significantly decreased in both Han and Uygur PDR patients. choroidal parameters analysis found that Uygur controls had substantially higher choroidal thickness (CT) than Han controls (p = 0.020) and PDR eyes showed significantly decreased CT. Both races with PDR exhibited significantly reduced choriocapillaris layer-VFD, large and medium choroidal vessel (LMCV) layer-VFD, CVV and CVI, however, Uygur PDR patients had significant lower LMCV layer-VFD, CVV and CVI compared to Han PDR patients. Diabetes duration was the most significant factor affecting CVV and CVI. CONCLUSION: Both Han and Uygur PDR patients had significantly lower CT and decreased vessel densities compared to controls, but the Uygur PDR patients had more severe choroidal damage than Han PDR patients, which is most likely related to worse visual prognosis. These findings indicate that more frequent screenings and prompt therapy are urgent for Uygur PDR patients.