Epigenetic-based combination therapy and liposomal codelivery overcomes osimertinib-resistant NSCLC via repolarizing tumor-associated macrophages.

Osimertinib (Osi) is widely used as a first-line treatment for non-small cell lung cancer (NSCLC) with EGFR mutations. However, the majority of patients treated with Osi eventually relapse within a year. The mechanisms of Osi resistance remain largely unexplored, and efficient strategies to reverse the resistance are urgently needed. Here, we developed a lactoferrin-modified liposomal codelivery system for the combination therapy of Osi and panobinostat (Pan), an epigenetic regulator of histone acetylation. We demonstrated that the codelivery liposomes could efficiently repolarize tumor-associated macrophages (TAM) from the M2 to M1 phenotype and reverse the epithelial-mesenchymal transition (EMT)-associated drug resistance in the tumor cells, as well as suppress glycolysis, lactic acid production, and angiogenesis. Our results suggested that the combination therapy of Osi and Pan mediated by liposomal codelivery is a promising strategy for overcoming Osi resistance in NSCLC.

Unlocking the potential of rice bran oil body as fat replacement in cookies: single and double crosslinked binary emulsion-filled gels based on lutein-loaded rice bran oil body emulsion.

BACKGROUND: Rice bran oil body is rich in nutritional value, which is a byproduct of rice processing. The aim of this study is to develop a novel emulsion-filled gel with lutein-loaded rice bran oil body and investigate its functionality as a fat replacer in cookies. The effects of incorporating structured oil body in the form of emulsion-filled gel instead of butter in cookies with a ratio of 0, 10, 20 and 50 wt% formulation were determined by measuring appearance, texture, thermodynamic properties, moisture distribution and microstructure. RESULTS: The results demonstrated the relationship between geometry, moisture and structure. The 20 wt% emulsion-filled gel substitution ratio yielded mobility and distribution abilities of melted fat and sugar in the cookies that were closest to those of butter. The addition of emulsion-filled gel increased the L* value and decreased the a* value, while the b* value of the cookie increased due to the advanced delivery of lutein by oil body. By controlling the addition ratio, the texture of the cookies can be adjusted. Starch granules were separated due to colloidal particles, reducing saturated fat content and decreasing cookie gelatinization enthalpy. The fat coating on starch particles enhanced the binding capacity of free water, improving air entrapment and forming a constrained gluten network structure. CONCLUSION: These findings provide a theoretical basis for rice bran oil body as a novel substitute for butter in the development of healthy, high-quality cookies. © 2024 Society of Chemical Industry.

Effects of removing phytic acid on the bioaccessibility of Ca/Fe/Zn and protein digestion in soymilk.

BACKGROUND: Soymilk is a high-quality source of protein and minerals, such as calcium (Ca), iron (Fe), and zinc (Zn). However, phytic acid in soymilk restricts mineral and protein availability. We here investigated the effects of removing phytic acid on the physicochemical properties, mineral (Ca, Fe, and Zn) bioaccessibility, and protein digestibility of soymilk. RESULTS: Physicochemical property analysis revealed that the removal of phytic acid reduced protein accumulation at the gastric stage, thereby facilitating soymilk matrix digestion. The removal of phytic acid significantly increased Zn bioaccessibility by 18.19% in low-protein soymilk and Ca and Fe bioaccessibility by 31.20% and 30.03%, respectively, in high-protein soymilk. CONCLUSION: Removing phytic acid was beneficial for the hydrolysis of high-molecular-weight proteins and increased the soluble protein content in soymilk, which was conducive to protein digestion. This study offers a feasible guide for developing plant-based milk with high nutrient bioaccessibility. © 2024 Society of Chemical Industry.

Retrospective analysis of 71 patients with cutaneous sporotrichosis.

OBJECTIVE: To summarise 71 cases of cutaneous sporotrichosis in Zhejiang over the past 9 years and analyse clinical and epidemiological characteristics. METHODS: This was a retrospective review of patients with cutaneous sporotrichosis attending the Department of Dermatology of the Hangzhou Third People's Hospital between 2013 and 2022. RESULTS: The male-to-female ratio was 1.15:1 among the 71 patients, with a mean age of 55.90 years (±2.02) and an age range of 3 to 94 years. The disease duration was unknown for 17 patients. The intermediate course for the remaining 54 patients lasted 11.90 months, ranging from 1 to 120 months. Thirty-four patients were involved in mixed occupations, 28 were farmers, 4 were housewives, 3 were manufacturing workers, and 2 were carpenters; 23.95% of cases had a history of trauma. The most common clinical manifestation was fixed cutaneous (69.01%), followed by lymphocutaneous (29.58%) and disseminated cutaneous (1.41%). There were 72 affected sites; the upper limbs (69.44%) were affected the most, followed by the face (16.67%) and lower limbs (12.50%). Forty-nine patients showed open lesions (69.01%), 15 showed mixed lesions (21.13%), and seven showed closed lesions (9.86%). Seventy-one patients were confirmed by biopsied tissue or tissue fluid culture. Forty-four patients underwent direct microscopy; of these, 18 (40.91%) were positive and 26 were negative. Molecular analysis confirmed that all fungal strains were Sporothrix globosa. Fifty-nine patients underwent histopathological examination, of whom 18 (18.64%) were positive for periodic acid-Schiff (PAS) staining. Eighteen patients were lost to follow-up; the remaining patients were cured. CONCLUSIONS: Consistent with the epidemiological situation of sporotrichosis in other areas of China, S. globosa is the primary pathogen in the Zhejiang province. The primary clinical form of sporotrichosis is fixed cutaneous. Susceptible subjects are mainly middle-aged and elderly rural populations, and males are affected more than females. Patients with cutaneous sporotrichosis do not commonly have a history of obvious trauma. Direct microscopy is important for the diagnosis of sporotrichosis, and itraconazole is a safe and effective treatment option.

Trichoscopy for early diagnosis and follow-up of pet-related neonatal tinea capitis.

We report infant zigzag hairs as a distinct trichoscopic sign for follow up a case of pet-related newborn tinea capitis due to Microsporum canis. Formation of infant zigzag hairs due to ectothrix M. canis infection may be associated soft neonatal widespread thin hair, which is different from vellus hair and terminal hair. In addition, tinea capitis was further confirmed by transmission electric microscopy and fungal culture. The patient was successfully treated by weekly oral fluconazole (8 mg/kg). Therefore, the handheld dermoscopy is a simple, non-invasive and very inexpensive technique for the diagnosis and follow-up of tinea capitis, especially for infant.

Bedside Diagnosis for Disseminated Deep Dermatophytosis: a Case Series Study.

Deep cutaneous fungal infections including deep dermatophytosis are responsible for significant morbidity and mortality, especially in immunocompromised patients. Variable and longer turnaround time on tissue culture results delay diagnosis. We sought to seek the fast bedside diagnosis for disseminated deep dermatophytosis by direct microscopy using a blunt scalpel or needle aspiration before biopsy. This is a 6-year retrospective review of patients with a diagnosis of disseminated deep dermatophytosis seen at a single tertiary care institution. Trichophyton rubrum was isolated in four patients, and T. mentagrophyte complex in one patient. All the dermatophyte isolates can grow at 37 °C. Microscopy of purulence sampling from intact nodules demonstrated abundant septate hyphae, and also isolation from purulence was concordance with skin tissue culture. Ultrasound-guided sampling from non-eroded can yield purulence, and direct microscopy of purulence may facilitate rapid diagnosis of deep dermatophytosis and serve to prevent disease progression and dissemination.

Abatement of Cd in rice grain and toxic risks to human health by the split application of silicon at transplanting and jointing period.

Silicon (Si) has the potential to ameliorate the toxic effects of cadmium (Cd) on rice growth and mitigate Cd-uptake by rice under Cd-contaminated soil. However, it is not completely clear whether there are differences in the impacts of different Si management on the chemical behavior of Cd in soil-rice system under Cd-contaminated paddy field. Here, pot trials were conducted to explore the effects of three modes of Si application (T-applying Si at transplanting stage, J-applying Si at jointing stage, TJ-applying Si at transplanting stage and jointing stage with a ratio of 50% to 50%) on the accumulation of Cd in rice grain and the toxic risk of Cd on human health in rice consumption under Cd-polluted soil (4.21 mg·kg-1), and that without Si application was used as control (CK). Results showed that rice growth and Cd-retention in root were enhanced by Si application, and the retention of Cd in TJ root was the highest, reaching 82.36%∼84.06% of total Cd absorbed by rice plant. TJ also elevated soil pH and CEC value significantly during the whole growth period, diminished Cd availability and converted exchangeable-Cd into residual-Cd in soil. Moreover, Si application reduced Cd concentration in iron plaque, while TJ had the lowest concentration of DCB-Cd and the highest molar ratios of Fe/Cd and Mn/Cd. The bioaccessibility of Cd from grains and cooked rice were decreased by Si application. Compared with T and J, the hazard quotient of digestion from cooked white rice of TJ in gastric phase was reduced by 19.61% and 21.94%, respectively. In brief, TJ had more efficiency on reducing the Cd availability in soil during the rice growing period, promoting the retention of Cd in root, decreasing Cd uptake by rice plant and distribution to grains, as well as the bioaccessibility of Cd from cooked rice. These results also provide a novel strategy of Si application to decrease the risk of Cd migration in the soil-rice-humans system and simultaneously promote rice yields.

Tinea capitis in children: A single-institution retrospective review from 2011 to 2019.

Tinea capitis remains a common public health problem worldwide, especially in developing countries. OBJECTIVES: To investigate the changes of the predominant dermatophytes of tinea capitis in children in Hangzhou in recent 9 years. METHODS: The age, gender and pathogen spectrum of 650 children with tinea capitis at the Department of Dermatology, Affiliated Third People's Hospital of Hangzhou, Anhui Medical University from 2011 to 2019 were analysed, and the distribution of pathogens from 1998 to 2000 was compared. RESULTS: Among the 650 cases, 340 cases (48.2%) were males and 310 cases (51.8%) were females. The main population infected with tinea capitis was children aged 0-10 years (620 cases, 95.4%). From 2011 to 2019, the predominant dermatophyte was changed from Trichophyton violaceum (2011) to Trichophyton mentagrophytes complex (2012-2015) and later to Microsporum canis (2016-2019). In the past 9 years, M. canis (250 cases, 38.5%) was the most common dermatophyte and followed by T mentagrophytes complex (209 cases, 32.2%). The dermatophyte spectrum was statistically different between the years 2011 and 2019 (Chi square: χ2  = 69.75, P < .05), and the differences in anthropophilic and zoophilic pathogens between 1989-2000 and 2011-2019 were statistically significant (χ2  = 24.4, P < .05). CONCLUSIONS: Research showed that children diagnosed with tinea capitis were mainly 0-10 years old. With age, the percentage of anthropophilic dermatophytes gradually increased, while the percentage of zoophilic dermatophytes decreased. M. canis was the predominant dermatophyte of tinea capitis in children, followed by T. mentagrophytes complex. The dermatophytes have shifted from anthropophilic to zoophilic dermatophytes in the past two decades.

Regulatory function of praja ring finger ubiquitin ligase 2 mediated by the P2rx3/P2rx7 axis in mouse hippocampal neuronal cells.

Praja2 (Pja2), a member of the growing family of mammalian RING E3 ubiquitin ligases, is reportedly involved in not only several types of cancer but also neurological diseases and disorders, but the genetic mechanism underlying the regulation of Pja2 in the nervous system remains unclear. To study the cellular and molecular functions of Pja2 in mouse hippocampal neuronal cells (MHNCs), we used gain- and loss-of-function manipulations of Pja2 in HT-22 cells and tested their regulatory effects on three Alzheimer's disease (AD) genes and cell proliferation. The results revealed that the expression of AD markers, including amyloid beta precursor protein (App), microtubule-associated protein tau (Mapt), and gamma-secretase activating protein (Gsap), could be inhibited by Pja2 overexpression and activated by Pja2 knockdown. In addition, HT-22 cell proliferation was enhanced by Pja2 upregulation and suppressed by its downregulation. We also evaluated and quantified the targets that responded to the enforced expression of Pja2 by RNA-Seq, and the results showed that purinergic receptor P2X, ligand-gated ion channel 3 and 7 (P2rx3 and P2rx7), which show different expression patterns in the critical calcium signaling pathway, mediated the regulatory effect of Pja2 in HT-22 cells. Functional studies indicated that Pja2 regulated HT-22 cells development and AD marker genes by inhibiting P2rx3 but promoting P2rx7, a gene downstream of P2rx3. In conclusion, our results provide new insights into the regulatory function of the Pja2 gene in MHNCs and thus underscore the potential relevance of this molecule to the pathophysiology of AD.

BCCIPß facilitates p53 ubiquitination via binding with E6 protein in high-risk HPV positive head and neck squamous cell carcinoma.

BRCA2 And CDKN1A Interacting Protein (BCCIP) is initially identified as a tumor suppressor. Some recent studies confirmed its p53 binding capability. In this study, we explored the regulatory effect of BCCIPß on p53 stability in HPV-positive and HPV-negative HNSCC cells. RNA-seq data from TCGA-HNSC were extracted for transcript isoform analysis in HPV-positive and HPV-negative tumors. HPV16-positive UM-SCC-47 (SCC47) and UM-SCC-104 (SCC104) and HPV-negative SCC-9 (SCC9) and UM-SCC-1 (SCC1) cell lines were used as in vitro cell models. Results showed that BCCIPß was the dominant transcript in both HPV-positive and HPV-negative HNSCC cases. Knockdown of BCCIPß decreased p53 protein concentration in the two HPV-negative cell lines but increased p53 concentration in the two HPV-positive cell lines. BCCIPß inhibition increased proliferation and G1/S transition of SCC9 and SCC1 cells. In comparison, BCCIPß inhibition slowed proliferation and increased G1 arrest of SCC104 and SCC47 cells. BCCIPß inhibition prolonged the half-life of p53 protein and reduced p53 ubiquitination in the two HPV16-positive cell lines. Co-IP assay confirmed interactions among BCCIPß, HPV E6, and p53 in both SCC104 and SCC47 cells. In comparison, only the interaction between BCCIPα and p53 was confirmed in these two cell lines. Either E6 or BCCIPß inhibition reduced p53 ubiquitination and increased p53 concentration. However, inhibiting E6 and BCCIPß at the same did not generate synergistic effects. On the contrary, p53 ubiquitination level was even higher in the combination group, with lower p53 concentration compared to the shE6 group. BCCIPß overexpression in SCC47 cells with HPV E6 depletion significantly reduced p53 ubiquitination. In conclusion, this study found a novel interaction between HPV E6 and BCCIPß in HPV16-positive HNSCC cells. The presence of HPV E6 turned BCCIPß from a p53 stabilizer to a ubiquitination facilitator. This mechanism helps explain why BCCIPß acted as a tumor suppressor in HPV-negative HNSCC but exerted oncogenic function in HPV16-positive HNSCC.

Favus of Scrotum Due to Trichophyton rubrum in Immunocompetent Patients: A Clinical, Mycological and Ultrastructural Study.

PURPOSE: To characterize the clinical and mycological features of favus of scrotum due to Trichophyton rubrum. METHODS: A single-site prospective study was carried out in an outpatient dermatology clinic. Microscopic examination and fungal culture were done using skin scrapings. Scales on the scrotum were stained with PAS and visualized by microscopy, including in vivo reflectance confocal microscopy (RCM). Two strains were analyzed by RAPD typing. Scutular lesions were fixed for scanning electron microscopy (SEM) and transmission electron microscopy (TEM). RESULTS: Cultures of the scale from the scrotum and/or groin in all patients showed a growth of T. rubrum. T. rubrum strains from scrotum and groins in one patient were demonstrated as the same strain by RAPD typing. The average age of patients was 34.1 ± 12.78 years. The mean course was 8.2 ± 5.07 days. All the patients received only topical treatment for 2 weeks without recurrence. Direct smear, calcofluor-white staining and in vivo RCM study of the scrotal favus in patients showed a massive number of septate branching hyphae, while fewer septate hyphae in scales in the groin. Abundant hyphae were found only in the outer layer of the stratum corneum of the scrotum under SEM and TEM with intact bilateral cell walls, and normal nucleus, liposomes and reticulum. Few distorted hyphae structures, cell wall degeneration, degenerated cytoplasm and the autophagy phenomenon could be seen in scales from groin under TEM. CONCLUSIONS: Scrotal favus due to T. rubrum is still a true infection, which most often occurred in immunocompetent patients.

Effects of PKM2 on global metabolic changes and prognosis in hepatocellular carcinoma: from gene expression to drug discovery.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor that threatens global human health. High PKM2 expression is widely reported in multiple cancers, especially in HCC. This study aimed to explore the effects of PKM2 on global gene expression, metabolic damages, patient prognosis, and multiple transcriptional regulation relationships, as well as to identify several key metabolic genes and screen some small-molecule drugs. METHODS: Transcriptome and clinical HCC data were downloaded from the NIH-GDC repository. Information regarding the metabolic genes and subsystems was collected from the Recon 2 human metabolic model. Drug-protein interaction data were obtained from the DrugBank and UniProt databases. We defined patients with PKM2 expression levels ≥11.25 as the high-PKM2 group, and those with low PKM2 expression (< 11.25) were defined as the low-PKM2 group. RESULTS: The results showed that the global metabolic gene expression levels were obviously divided into the high- or low-PKM2 groups. In addition, a greater number of affected metabolic subsystems were observed in the high-PKM2 group. Furthermore, we identified 98 PKM2-correlated deregulated metabolic genes that were associated with poor overall patient survival. Together, these findings suggest more comprehensive influences of PKM2 on HCC. In addition, we screened several small-molecule drugs that target these metabolic enzymes, some of which have been used in antitumor clinical studies. CONCLUSIONS: HCC patients with high PKM2 expression showed more severe metabolic damage, transcriptional regulation imbalance and poor prognosis than low-PKM2 individuals. We believe that our study provides valuable information for pathology research and drug development for HCC.

Folate Deficiency and Gene Polymorphisms of MTHFR, MTR and MTRR Elevate the Hyperhomocysteinemia Risk.

BACKGROUND: Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular diseases (CVDs). We aimed to investigate the joint effect of homocysteine metabolism gene polymorphisms, as well as the folate deficiency on the risk of HHcy in a Chinese hypertensive population. METHODS: This study enrolled 480 hypertensive patients aged 28 - 75 from six hospitals in different Chinese regions from 9/2005 - 12/2005. Known genotypes of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, and methionine synthase reductase (MTRR) A66G were detected by PCRRFLP methods. Serum Hcy was measured by high-performance liquid chromatography and serum folate was measured by chemiluminescent immunoassay. RESULTS: MTHFR C677T and MTR A2756G can independently elevate the risk of HHcy (TT vs. CC + CT, p < 0.001 and AG + GG vs. AA, p = 0.026, respectively), whereas MTHFR A1298C decreased HHcy risk (AC + CC vs. AA, p < 0.001) and showed a protective effect against HHcy risk. Importantly, the joint effect of these risk genotypes showed significantly higher odds of HHcy than non-risk genotypes, especially the patients with four risk genotypes. It is noteworthy that this deleterious effect was aggravated by folate deficiency. These findings were verified by generalized multifactor dimensionality reduction model (p = 0.001) and a cumulative effects model (p < 0.001). CONCLUSIONS: We have first demonstrated that the joint effect of homocysteine metabolism gene polymorphisms and folate deficiency lead to dramatic elevations in the HHcy risk.

Joint associations of folate, homocysteine and MTHFR, MTR and MTRR gene polymorphisms with dyslipidemia in a Chinese hypertensive population: a cross-sectional study.

BACKGROUND: Dyslipidemia is a well-established risk factor for cardiovascular disease. Serum lipids were affected by several gene polymorphisms, folate, homocysteine and other metabolite levels. We aim to investigate the effects of homocysteine metabolism enzyme polymorphisms (MTHTR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) and their interactions with folate, homocysteine on serum lipid levels in Chinese patients with hypertension. METHODS: Participants were 480 hypertensive adults that enrolled in September to December 2005 from six different Chinese hospitals (Harbin, Shanghai, Shenyang, Beijing, Xi'an, and Nanjing). Known MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G genotypes were determined by PCR-RFLP methods. Serum folate was measured by chemiluminescent immunoassay, homocysteine was measured by high-performance liquid chromatography, serum lipids parameters were determined by an automatic biochemistry analyzer, low-density lipoprotein was calculated by Friedewald's equation. Unitary linear regression model was used to assess the associations of gene polymorphisms, folate and homocysteine on serum lipid profiles. Unconditional logistic regression model was applied to test the interactions of folate, homocysteine and gene polymorphisms on dyslipidemia. RESULTS: No correlations between gene polymorphisms and homocysteine on serum lipid profiles. Compared with normal folate patients, patients with low folate showed higher odds of hypertriglyceridemia (OR = 2.02, 95 % CI: 1.25-3.25, P = 0.004) and low levels of high-density lipoprotein cholesterol (OR = 1.88, 95 % CI: 1.07-3.28, P = 0.027). Each of four gene polymorphisms (MTHTR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) combined with low folate showed higher odds of hypertriglyceridemia (P for trend: 0.049, 0.004, 0.007 and 0.005, respectively). MTHFR C677T and A1298C with low folate showed higher odds of low levels of high-density lipoprotein cholesterol (P for trend: 0.008 and 0.031). CONCLUSIONS: Low folate status and homocysteine metabolism gene polymorphisms (MTHTR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) may have a synergistic effect increased the incidence of dyslipidemia in Chinese hypertensive population.

Depletion of histone deacetylase 3 antagonizes PI3K-mediated overgrowth of Drosophila organs through the acetylation of histone H4 at lysine 16.

Core histone modifications play an important role in chromatin remodeling and transcriptional regulation. Histone acetylation is one of the best-studied gene modifications and has been shown to be involved in numerous important biological processes. Herein, we demonstrated that the depletion of histone deacetylase 3 (Hdac3) in Drosophila melanogaster resulted in a reduction in body size. Further genetic studies showed that Hdac3 counteracted the organ overgrowth induced by overexpression of insulin receptor (InR), phosphoinositide 3-kinase (PI3K) or S6 kinase (S6K), and the growth regulation by Hdac3 was mediated through the deacetylation of histone H4 at lysine 16 (H4K16). Consistently, the alterations of H4K16 acetylation (H4K16ac) induced by the overexpression or depletion of males-absent-on-the-first (MOF), a histone acetyltransferase that specifically targets H4K16, resulted in changes in body size. Furthermore, we found that H4K16ac was modulated by PI3K signaling cascades. The activation of the PI3K pathway caused a reduction in H4K16ac, whereas the inactivation of the PI3K pathway resulted in an increase in H4K16ac. The increase in H4K16ac by the depletion of Hdac3 counteracted the PI3K-induced tissue overgrowth and PI3K-mediated alterations in the transcription profile. Overall, our studies indicated that Hdac3 served as an important regulator of the PI3K pathway and revealed a novel link between histone acetylation and growth control.

Isoindolone derivative QSN-10c induces leukemic cell apoptosis and suppresses angiogenesis via PI3K/AKT signaling pathway inhibition.

AIM: 2-(4,6-Dimethoxy-1,3-dioxoisoindolin-2-yl) ethyl 2-chloroacetate (QSN-10c) is one of isoindolone derivatives with antiproliferative activity against human umbilical vein endothelial cells (HUVECs). The aim of this study was to investigate its antitumor activity in vitro and anti-angiogenic effects in vitro and in vivo. METHODS: K562 leukemic cells and HUVECs were used for in vitro studies. Cell viability was examined using MTT assay. Cell apoptosis and mitochondrial transmembrane potential (Δψm) were detected with flow cytometry. Tube formation and migration of HUVECs were studied using two-dimensional Matrigel assay and wound-healing migration assay, respectively. VEGF levels were analyzed with RT-PCR and Western blotting. A zebrafish embryo model was used for in vivo anti-angiogenic studies. The molecular mechanisms for apoptosis in K562 cells and antiangiogenesis were measured with Western blotting. RESULTS: In antitumor activity studies, QSN-10c suppressed the viability of K562 cells and induced apoptosis in dose- and time-dependent manners. Furthermore, QSN-10c dose-dependently decreased the Δψm in K562 cells, increased the release of cytochrome c and the level of Bax, and decreased the level of Bcl-2, suggesting that QSN-10c-induced apoptosis of K562 cells was mediated via the mitochondrial apoptotic pathway. In anti-angiogenic activity studies, QSN-10c suppressed the viability of HUVECs and induced apoptosis in dose dependent manners. QSN-10c treatment did not alter the Δψm in HUVECs, but dose-dependently inhibited the expression of VEGF, inhibited the tube formation and cell migration in vitro, and significantly suppressed the number of ISVs in zebrafish embryos in vivo. Furthermore, QSN-10c dose-dependently suppressed the phosphorylation of AKT and GSK3ß in both HUVECs and K562 cells. CONCLUSION: QSN-10c is a novel antitumor compound that exerts both antitumor and anti-angiogenic effects via inhibiting the PI3K/AKT/GSK3ß signaling pathway.

Alternations of Blood Pressure Following Surgical or Drug Therapy for Prolactinomas.

Several subtypes of pituitary neuroendocrine tumors (PitNETs), such as acromegaly and Cushing's disease, can result in hypertension. However, whether prolactinoma is associated with this complication remains unknown. Moreover, the effect of treatment with surgery or drugs on blood pressure (BP) is unknown. Herein, a retrospective study reviewed 162 patients with prolactinoma who underwent transsphenoidal surgery between January 2005 and December 2022. BP measurements were performed 1 day before and 5 days after surgery. Accordingly, patients' medical characteristics were recorded. In addition, in situ rat and xenograft nude-mice prolactinoma models have been used to mimic prolactinoma. In vivo BP and serum prolactin (PRL) levels were measured after cabergoline (CAB) administration in both rats and mice. Our data suggest that surgery can effectively decrease BP in prolactinoma patients with or without hypertension. The BP-lowering effect was significantly associated with several variables, including age, sex, disease duration, tumor size, invasion, dopamine agonists (DAs)-resistance, recurrence, and preoperative PRL levels. Moreover, in situ and xenograft prolactinomas induced BP elevation, which was alleviated by CAB treatment without and with a statistical difference in rats and mice, respectively. Thus, surgery or CAB can decrease BP in prolactinoma, indicating that pre- and postoperative BP management becomes essential.

Mediating peroxymonosulfate activation path in Fenton-like reaction via doping different metal atoms into g-C3N5.

Peroxymonosulfate (PMS) could be activated by either radical path or non-radical path, how to rationally mediate these two routines was an important unresolved issue. This work has introduced a simple way to address this problem via metal atom doping. It was found that Fe-doped nitrogen-rich graphitic carbon nitride (Fe-C3N5) exhibited high activity towards PMS activation for tetracycline degradation, and the degradation rate was 3.14 times higher than that of Co-doped nitrogen-rich graphitic carbon nitride (Co-C3N5). Radical trapping experiment revealed the contributions of reactive species over two catalysts were different. Electron paramagnetic resonance analysis further uncovered the non-radical activation path played a dominated role on Fe-C3N5 surface, while the radical activation path was the main routine on Co-C3N5 surface. Density functional theory calculations, X-ray photoelectron spectroscopy analysis, and electrochemical experiments provided convincing evidence to support these views. This study supplied a novel method to mediate PMS activation path via changing the doped metal atom in g-C3N5 skeleton, and it allowed us to better optimize the PMS activation efficiency.

Harnessing TME depicted by histological images to improve cancer prognosis through a deep learning system.

Spatial transcriptomics (ST) provides insights into the tumor microenvironment (TME), which is closely associated with cancer prognosis, but ST has limited clinical availability. In this study, we provide a powerful deep learning system to augment TME information based on histological images for patients without ST data, thereby empowering precise cancer prognosis. The system provides two connections to bridge existing gaps. The first is the integrated graph and image deep learning (IGI-DL) model, which predicts ST expression based on histological images with a 0.171 increase in mean correlation across three cancer types compared with five existing methods. The second connection is the cancer prognosis prediction model, based on TME depicted by spatial gene expression. Our survival model, using graphs with predicted ST features, achieves superior accuracy with a concordance index of 0.747 and 0.725 for The Cancer Genome Atlas breast cancer and colorectal cancer cohorts, outperforming other survival models. For the external Molecular and Cellular Oncology colorectal cancer cohort, our survival model maintains a stable advantage.