Benzo[a]pyrene evokes epithelial-mesenchymal transition and pulmonary fibrosis through AhR-mediated Nrf2-p62 signaling.

Benzo[a]pyrene (BaP) and its metabolic end product benzo(a)pyren-7,8-dihydrodiol-9,10-epoxide (BPDE), are known toxic environmental pollutants. This study aimed to analyze whether sub-chronic BPDE exposure initiated pulmonary fibrosis and the potential mechanisms. In this work, male C57BL6/J mice were exposed to BPDE by dynamic inhalation exposure for 8 weeks. Our results indicated that sub-chronic BPDE exposure evoked pulmonary fibrosis and epithelial-mesenchymal transition (EMT) in mice. Both in vivo and in vitro, BPDE exposure promoted nuclear translocation of Snail. Further experiments indicated that nuclear factor erythroid 2-related factor 2 (Nrf2) and p62 were upregulated in BPDE-exposed alveolar epithelial cells. Moreover, Nrf2 siRNA transfection evidently attenuated BPDE-induced p62 upregulation. Besides, p62 shRNA inhibited BPDE-incurred Snail nuclear translocation and EMT. Mechanically, BPDE facilitated physical interaction between p62 and Snail in the nucleus, then repressed Snail protein degradation by p62-dependent autophagy-lysosome pathway, and finally upregulated transcriptional activity of Snail. Additionally, aryl hydrocarbon receptor (AhR) was activated in BPDE-treated alveolar epithelial cells. Dual-luciferase assay indicated activating AhR could bind to Nrf2 gene promoter. Moreover, pretreatment with CH223191 or α-naphthoflavone (α-NF), AhR antagonists, inhibited BPDE-activated Nrf2-p62 signaling, and alleviated BPDE-induced EMT and pulmonary fibrosis in mice. Taken together, AhR-mediated Nrf2-p62 signaling contributes to BaP-induced EMT and pulmonary fibrosis.

Down-regulation of AKT proteins slows the growth of mutant-KRAS pancreatic tumors.

Serine/threonine kinase AKT isoforms play a well-established role in cell metabolism and growth. Most pancreatic adenocarcinoma (PDAC) harbors activation mutations of KRAS, which activates the PI3K/AKT signaling pathway. However, AKT inhibitors are not effective in the treatment of pancreatic cancer. To better understand the role of AKT signaling in mutant-KRAS pancreatic tumors, this study utilizes proteolysis-targeting chimeras (PROTACs) and CRISPR-Cas9-genome editing to investigate AKT proteins. PROTAC down-regulation of AKT proteins markedly slowed the growth of three pancreatic tumor cell lines harboring mutant KRAS. In contrast, inhibition of AKT kinase activity alone had very little effect on the growth of these cell lines. Concurrent genetic deletion of all AKT isoforms (AKT1, AKT2, and AKT3) in the KPC (KrasG12D; Trp53R172H; Pdx1-Cre) pancreatic cancer cell line also dramatically slowed its growth in vitro and when orthotopically implanted in syngeneic mice. Surprisingly, insulin-like growth factor-1 (IGF-1), but not epidermal growth factor (EGF), restored KPC cell growth in serum-deprived conditions and the IGF-1 growth stimulation effect was AKT dependent. RNA-seq analysis of AKT1/2/3-deficient KPC cells suggested that reduced cholesterol synthesis may be responsible for the decreased response to IGF-1 stimulation. These results indicate that the presence of all three AKT isoforms supports pancreatic tumor cell growth and pharmacological degradation of AKT proteins may be more effective than AKT catalytic inhibitors for treating pancreatic cancer.

Highly Stretchable Double Network Ionogels for Monitoring Physiological Signals and Detecting Sign Language.

At the heart of the non-implantable electronic revolution lies ionogels, which are remarkably conductive, thermally stable, and even antimicrobial materials. Yet, their potential has been hindered by poor mechanical properties. Herein, a double network (DN) ionogel crafted from 1-Ethyl-3-methylimidazolium chloride ([Emim]Cl), acrylamide (AM), and polyvinyl alcohol (PVA) was constructed. Tensile strength, fracture elongation, and conductivity can be adjusted across a wide range, enabling researchers to fabricate the material to meet specific needs. With adjustable mechanical properties, such as tensile strength (0.06-5.30 MPa) and fracture elongation (363-1373%), this ionogel possesses both robustness and flexibility. This ionogel exhibits a bi-modal response to temperature and strain, making it an ideal candidate for strain sensor applications. It also functions as a flexible strain sensor that can detect physiological signals in real time, opening doors to personalized health monitoring and disease management. Moreover, these gels' ability to decode the intricate movements of sign language paves the way for improved communication accessibility for the deaf and hard-of-hearing community. This DN ionogel lays the foundation for a future in which e-skins and wearable sensors will seamlessly integrate into our lives, revolutionizing healthcare, human-machine interaction, and beyond.

Bridging metabolic syndrome and cognitive dysfunction: role of astrocytes.

Metabolic syndrome (MetS) and cognitive dysfunction pose significant challenges to global health and the economy. Systemic inflammation, endocrine disruption, and autoregulatory impairment drive neurodegeneration and microcirculatory damage in MetS. Due to their unique anatomy and function, astrocytes sense and integrate multiple metabolic signals, including peripheral endocrine hormones and nutrients. Astrocytes and synapses engage in a complex dialogue of energetic and immunological interactions. Astrocytes act as a bridge between MetS and cognitive dysfunction, undergoing diverse activation in response to metabolic dysfunction. This article summarizes the alterations in astrocyte phenotypic characteristics across multiple pathological factors in MetS. It also discusses the clinical value of astrocytes as a critical pathologic diagnostic marker and potential therapeutic target for MetS-associated cognitive dysfunction.

Association of two novel systemic inflammatory biomarkers and frailty based on NHANES 2007-2018.

Background: Frailty is a significant concern in the field of public health. However, currently, there is a lack of widely recognized and reliable biological markers for frailty. This study aims to investigate the association between systemic inflammatory biomarkers and frailty in the older adult population in the United States. Methods: This study employed data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2018 and conducted a rigorous cross-sectional analysis. We constructed weighted logistic regression models to explore the correlation between the Systemic Immune-Inflammation Index (SII), Systemic Inflammatory Response Index (SIRI), and frailty in the population aged 40 to 80 years. Using restricted cubic spline (RCS), we successfully visualized the relationship between SII, SIRI, and frailty. Finally, we presented stratified analyses and interaction tests of covariates in a forest plot. Results: This study involved 11,234 participants, 45.95% male and 54.05% female, with an average age of 64.75 ± 0.13 years. After adjusting for relevant covariates, the weighted logistic regression model indicated an odds ratio (OR) and 95% confidence interval(CI) for the correlation between frailty and the natural logarithm (ln) transformed lnSII and lnSIRI as 1.38 (1.24-1.54) and 1.69 (1.53-1.88), respectively. Subsequently, we assessed different levels of lnSII and lnSIRI, finding consistent results. In the lnSII group model, the likelihood of frailty significantly increased in the fourth quartile (OR = 1.82, 95% CI: 1.55-2.12) compared to the second quartile. In the lnSIRI group model, the likelihood of frailty significantly increased in the third quartile (OR = 1.30, 95% CI: 1.10-1.53) and fourth quartile (OR = 2.29, 95% CI: 1.95-2.70) compared to the second quartile. The interaction results indicate that age and income-to-poverty ratio influence the association between lnSIRI and frailty. RCS demonstrated a nonlinear relationship between lnSII, lnSIRI, and frailty. Conclusion: The results of this cross-sectional study indicate a positive correlation between systemic inflammatory biomarkers (SII, SIRI) and frailty.

The influence of hydrogen bonding on the structure of organic-inorganic hybrid catalysts and its application in the solvent-free epoxidation of α-olefins.

In this study, two types of catalysts were prepared by the combination of gemini quaternary ammonium salt with two distinct species of phosphotungstic acid. Catalysts prepared by the Wells-Dawson type of phosphotungstic acid and Keggin-type phosphotungstic acid both exhibited dual-phase catalytic behavior, demonstrating both heterogeneous and homogeneous catalytic activities. In comparison to the catalyst prepared by the Keggin-type phosphotungstic acid, due to the higher size of Wells-Dawson type of phosphotungstic acid, hydrogen bonding could not effectively affect the catalyst prepared by H6P2W18O62. Subsequently, the influential factors on the catalytic reaction were investigated. Through the utilization of techniques such as XPS, FT-IR, Raman spectra and other characterization methods, two distinct structure and reaction mechanisms for these catalysts were elucidated under the influence of hydrogen bonding.

Facile Synthesis of Dual-Network Polymer Hydrogels with Anti-Freezing, Highly Conductive, and Self-Healing Properties.

We report the synthesis of poly(acrylamide-co-acrylic acid)/sodium carboxy methyl cellulose (PAMAA/CMC-Na) hydrogels, and subsequent fabrication of dual-network polymer hydrogels (PAMAA/CMC-Na/Fe) using as-prepared via the salt solution (FeCl3) immersion method. The created dual-network polymer hydrogels exhibit anti-swelling properties, frost resistance, high conductivity, and good mechanical performance. The hydrogel swells sightly when immersed in solution (pH = 2~11). With the increase in nAA:nAM, the modulus of elasticity experiences a rise from 1.1 to 1.6 MPa, while the toughness undergoes an increase from 0.18 to 0.24 MJ/m3. Furthermore, the presence of a high concentration of CMC-Na also contributes to the enhancement of mechanical strength in the resulting hydrogels, ascribing to enhanced physical network of the hydrogels. The minimum freezing point reaches -21.8 °C when the CMC-Na concentration is 2.5%, owing to the dissipated hydrogen bonds by the coordination of Fe3+ with carboxyl (-COO-) in CMC-Na and PAMAA. It is found that the conductivity of the PAMAA/CMC-Na/Fe hydrogels gradually decreased from 2.62 to 0.6 S/m as the concentration of CMC-Na rises. The obtained results indicates that the dual-network hydrogels with high mechanical properties, anti-swelling properties, frost resistance, and electrical conductivity can be a competitive substance used in the production of bendable sensors and biosensors.

Analysis of related factors for neuropsychiatric comorbidities in children with epilepsy.

OBJECTIVE: To analyze the risk factors affecting psychiatric behavior and study the psychobehavioral conditions of children with epilepsy. METHOD: We randomly selected and enrolled 294 children with epilepsy who visited and were hospitalized in the pediatric clinic of Hebei General Hospital between January 2017 and January 2022, as the study participants. We comprehensively assessed their cognitive functions using the Gesell development schedule or Wechsler Intelligence Scales. The participants were divided into the study group (n = 123) with cognitive impairment and the control group (n = 171) with normal cognitive functions, for analysis. RESULTS: There were statistically significant differences between the two groups in disease course, frequency of epilepsy, status epilepticus, and the number of antiseizure medications (ASMs) used (P < 0.05), while there were no statistically significant differences in age, gender, age of onset, form of onset, interictal epileptiform discharge, history of febrile convulsion, and the time from onset to initial visit (P > 0.05). Based on multivariate logistic regression analysis, the course of disease, frequency of onset, status epilepticus and number of ASMs used were identified as high-risk factors for cognitive impairment in children with epilepsy. Similarly, early onset, long course of disease, known etiology, and combination of multiple drugs have a negative impact on behavioral problems, school education, and social adaptability. CONCLUSION: The course of disease, the frequency of onset, status epilepticus, and the number of ASMs used are high-risk factors for cognitive impairment in children with epilepsy, which can be prevented and controlled early. When selecting ASMs, their advantages and disadvantages should be weighed. Moreover, the availability of alternative treatment options must be considered. With the help of genomic technology, the causes of epilepsy should be identified as early as possible, and precision medicine and gene therapy for children with epilepsy should be actively developed.

Evaluation of the efficacy and safety of endoscopic band ligation in the treatment of bleeding from mild to moderate gastric varices type 1.

BACKGROUND: According to practice guidelines, endoscopic band ligation (EBL) and endoscopic tissue adhesive injection (TAI) are recommended for treating bleeding from esophagogastric varices. However, EBL and TAI are known to cause serious complications, such as hemorrhage from dislodged ligature rings caused by EBL and hemorrhage from operation-related ulcers resulting from TAI. However, the optimal therapy for mild to moderate type 1 gastric variceal hemorrhage (GOV1) has not been determined. Therefore, the aim of this study was to discover an individualized treatment for mild to moderate GOV1. AIM: To compare the efficacy, safety and costs of EBL and TAI for the treatment of mild and moderate GOV1. METHODS: A clinical analysis of the data retrieved from patients with mild or moderate GOV1 gastric varices who were treated under endoscopy was also conducted. Patients were allocated to an EBL group or an endoscopic TAI group. The differences in the incidence of varicose relief, operative time, operation success rate, mortality rate within 6 wk, rebleeding rate, 6-wk operation-related ulcer healing rate, complication rate and average operation cost were compared between the two groups of patients. RESULTS: The total effective rate of the two treatments was similar, but the efficacy of EBL (66.7%) was markedly better than that of TAI (39.2%) (P < 0.05). The operation success rate in both groups was 100%, and the 6-wk mortality rate in both groups was 0%. The average operative time (26 min) in the EBL group was significantly shorter than that in the TAI group (46 min) (P < 0.01). The rate of delayed postoperative rebleeding in the EBL group was significantly lower than that in the TAI group (11.8% vs 45.1%) (P < 0.01). At 6 wk after the operation, the healing rate of operation-related ulcers in the EBL group was 80.4%, which was significantly greater than that in the TAI group (35.3%) (P < 0.01). The incidence of postoperative complications in the two groups was similar. The average cost and other related economic factors were greater for the EBL than for the TAI (P < 0.01). CONCLUSION: For mild to moderate GOV1, patients with EBL had a greater one-time varix eradication rate, a greater 6-wk operation-related ulcer healing rate, a lower delayed rebleeding rate and a lower cost than patients with TAI.

Quantitative Analysis of the Instant and Persistent Inhibition Effects of Maternal Poliovirus Antibodies on the Immune Response in a Phase IV Trial of a Sabin Strain-Based Inactivated Poliovirus Vaccine.

BACKGROUND: An inactivated poliomyelitis vaccine made from Sabin strains (sIPVs) has widely been used in China since 2015. However, the quantitative data on the instant and persistent inhibition effects of maternal poliovirus antibodies on the immune response to sIPV priming and booster vaccination have not been available yet. OBJECTIVE: In this study, we aim to explore and quantify the instant and persistent inhibition effect of maternal poliovirus antibodies on the immune response elicited by sIPV primary and booster vaccination. METHODS: The immunogenicity data consisting of the days 0 and 30 after the prime and booster vaccination of the sIPV in a phase IV trial were pooled for a quantitative analysis of the inhibition effect of maternal poliovirus antibody. The geometric mean ratio (GMR) was calculated using linear regression models, representing that every 2-fold higher maternal poliovirus antibody titer may result in a (1-GMR) lower postimmunization antibody titer. RESULTS: The GMRs for poliovirus types 1, 2, and 3 were 0.79 (0.77-0.82), 0.85 (0.81-0.89), and 0.87 (0.83-0.91) at 30 days after the priming series, 0.86 (0.83-0.89), 0.81 (0.76-0.85), and 0.86 (0.80-0.93) at one year after the priming series, and 0.96 (0.94-0.99), 0.89 (0.86-0.93), and 0.98 (0.93-1.03) at 30 days after the booster dose. The inhibition effect continued to exist until the booster dose 1 year later, and such a persistent inhibition effect was almost attenuated for poliovirus types 1 and 3, and partly reduced for type 2 at 30 days after the booster dose. CONCLUSION: A wider interval between the four sIPV doses might be a consideration for reducing the effect of maternal antibodies and subsequently eliciting and maintaining higher antibody levels to protect against poliovirus transmission and infection at the final stage of polio eradication in the global world. This study's clinical trial registry number is NCT04224519.

[Clinical Significance of Genetic and Molecular Changes in Primary Myeloid Sarcoma].

OBJECTIVE: To investigate the clinical significance of genetic and molecular changes in primary myeloid sarcoma (MS). METHODS: Fourteen patients with primary MS were selected in Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, The First People's Hospital of Lianyungang from September 2010 to December 2021. AML1-ETO fusion, PML-RARα fusion and CBFß breakage were detected by fluorescence in situ hybridization (FISH), and the mutations of NPM1, CEBPA, FLT3, RUNX1, ASXL1, KIT and TP53 genes were detected by new generation sequencing (NGS). RESULTS: Among 14 patients, the MS occurred in bone, breast, epididymis, lung, chest wall, cervix, small intestine, ovary, lymph nodes and central nervous system. The tumor cells expressed MPO (13 cases), CD34 (7 cases), CD43 (8 cases), CD68 (7 cases), CD99 (8 cases) and CD117 (6 cases). Cytogenetic abnormalities were observed in 4 cases, including 3 cases of AML1-ETO fusion and 1 case of CBFß breakage, while no PML-RARα fusion was detected. There were no significant differences in overall survival (OS) and leukemia-free survival (LFS) between patients with and without AML1-ETO fusion/CBFß breakage (both P >0.05). Among the 14 patients, the number of NPM1, CEBPA, FLT3-ITD, RUNX1, ASXL1, KIT and TP53 gene mutations was 5, 3, 5, 3, 2, 2, 1, respectively, of which 7 cases had at least one mutation in FLT3-ITD, RUNX1, ASXL1 and TP53 gene. The OS and LFS of patients with FLT3-ITD, RUNX1, ASXL1 or TP53 mutation were shorter than those without mutations (both P <0.01). CONCLUSION: The genetic and molecular abnormalities of primary MS can be detected by FISH and NGS techniques. FLT3-ITD, RUNX1, ASXL1 or TP53 mutation indicates a worse prognosis, but further clinical studies are needed to confirm it.

Immunogenicity and lot-to-lot consistency of booster shot with Sabin inactivated poliomyelitis vaccine in Chinese children aged 18-24 Months: A phase â £ clinical trial.

BACKGROUND: There has been no data on the immunogenicity and safety of the 4th booster dose of the sIPV immunization in 18-24 months old children in post-marketing studies of large cohort providing with robust results. METHOD: In a phase Ⅳ randomized, double-blinded clinical trial, 1200 participants aged 2 months were immunized with three consecutive doses of sIPV at 2, 3, and 4 months old to complete primary immunization. Out of the 1200 participants, 1129 received the 4th dose of sIPV as booster immunization. Immunogenicity was evaluated in 1100 participants. RESULTS: Seropositive rates of the anti-poliovirus type 1, 2, and 3 neutralizing antibodies were 99.9 %, 98.0 %, 98.2 %, respectively, with GMTs of 557.0, 146.1, 362.0 one year after primary vaccination. After booster vaccination between 18 and 24 months old, the seropositive rates for 3 types all reached 100.0 %, with GMTs of 8343.6, 5039.6, 5492.0, respectively. Particularly for the anti-poliovirus type 2 antibody, the GMT was 230.4 after primary immunization, maintained to 146.1 one year after primary immunization, and increased to as high as 5039.6 after booster vaccination. The GMT ratios between each batch groups after booster immunization were between 0.67 and 1.50, meeting the immunological equivalence criteria. The incidence rate of adverse reaction was 23.0 %, which was comparable to those in the phase Ⅲ trial but had a lower incidence. Furthermore, no SUSAR was reported in this study. INTERPRETATION: In conclusion, as the anti-poliovirus antibodies gradually waned one year post sIPV primary vaccination, especially the type 2 antibody waned to a very low level, suggesting the importance of the booster immunization for children at the age of 18-24 months old. The booster shot can greatly enhance the antibody level and protect children from the potential risk of infection with WPV and VDPV by supplementing the anti-poliovirus type 2 immunity gap in the current real world. Clinic Trial Registration. NCT04224519.

Non-Noble-Metal-Doped Carbon Nitride Photocatalysts for Water Splitting Screened Out by Empty Defect States and the d-Band Center.

A rational design of water-splitting photocatalysts from the perspective of the electronic structure is highly desirable for optimizing catalytic activities. However, the structure-activity relationship is still unclear, which impedes the development of efficient catalysts. Herein, by comparing systematically the overall water-splitting capability of 20 kinds of metallic elements anchored at three sites (including cavity, carbon vacancy, and nitrogen vacancy) of graphitic carbon nitride (g-C3N4) through density functional theory calculations, we uncover that availability of in-gap empty defect states and the d-band center position are paramount parameters to determine activities of g-C3N4 on photocatalytic water splitting. In-gap empty states play a role in accommodating electrons from H2O to facilitate its splitting. A lower d-band center weakens the interaction between reaction intermediates and g-C3N4, thereby promoting O2 desorption. Metals embedded at carbon vacancies are found to be superior to those at cavities and nitrogen vacancies because the former not only provides ample in-gap empty states but also has a lower d-band center. We also discover a rule that, for a reaction in which the bond order between the metal and intermediate enlarges (reduces), its reaction difficulty increases (decreases) with the increasing atomic number for elements in the same period. After screening, we find that non-noble metals Co, Ni, and Ga anchored at carbon vacancies possess catalytic performances comparable to Pd- and Pt-doped systems, with the rate-determining barriers less than 0.55 eV. Our findings may provide useful information for designing effective photocatalysts.

Association between fecal short-chain fatty acid levels and constipation severity in subjects with slow transit constipation.

OBJECTIVE: We measured the fecal levels of short-chain fatty acids (SCFAs) in subjects with slow transit constipation (STC) and assessed the correlation between SCFA levels and disease severity as well as quality of life. METHODS: We isolated the supernatant from fecal samples of healthy and STC subjects and measured the SCFA levels. To assess the correlation between fecal SCFA levels and disease severity as well as quality of life, we used the Constipation Scoring System, Patient Assessment of Constipation Symptoms, and Patient Assessment of Constipation Quality of Life questionnaires. RESULTS: 16 STC subjects and 16 healthy controls were enrolled. STC subjects had lower SCFA levels, but the difference was not statistically significant (475.85 ±â€…251.68 vs. 639.77 ±â€…213.97 µg/ml, P = 0.056). Additionally, STC subjects had lower acetic and propionic acid levels (149.06 ±â€…88.54 vs. 261.33 ±â€…109.75 µg/ml and 100.60 ±â€…60.62 vs. 157.34 ±â€…66.37 µg/ml, respectively, P < 0.05) and higher isobutyric and isovaleric acid levels (27.21 ±â€…15.06 vs. 18.16 ±â€…8.65 µg/ml and 31.78 ±â€…18.81 vs. 16.90 ±â€…10.05 µg/ml, respectively, P < 0.05). At 252.21 µg/ml acetic acid, the specificity and sensitivity to distinguish healthy from STC subjects were 93.7% and 56.3%, respectively. In STC subjects, there were significant negative correlations between acetic and propionic acid levels and Constipation Scoring System scores. CONCLUSION: Fecal SCFA, acetic acid, and propionic acid levels decreased in STC subjects. There were significant negative correlations between the levels of the two acids and constipation severity.

High-efficiency and sustainable sodium humate aerogel evaporator for solar steam generation.

The utilization of solar interface evaporation technology (SIET) for freshwater production from seawater and sewage is a sustainable, green, viable, and promising approach. However, the absorption rate of sunlight, evaporation rates, and high costs still pose large-scale solar steam generation. In this paper, a novel aerogel (named SAS) was prepared by graft copolymerization with sodium alginate (SA), acrylic acid (AA) and sodium humate (SH) in aqueous solution, using N, N'-Methylenebisacrylamide (MBA) as crosslinker and ammonium persulfate (APS) as initiator, which has high light absorption (90 %), high porosity (87.96 %), superhydrophilicity (35 ms), low thermal conductivity (0.23 W m-1 k-1). The evaporation rate of SAS aerogel can reach up to 1.66 kg m-2h-1 under 1 kW m-2 light intensity, and the reusability and reliability of SAS aerogel are verified by 10 cycles of experiments. The utilization of this SAS aerogel holds significant implications for the design and fabrication of cost-effective, high-performance solar steam evaporation systems, thereby offering promising solutions to address global freshwater shortages and enhance wastewater treatment efficiency.

Study on the epoxidation of chain olefins using biquaternary ammonium phosphotungstic acid phase transfer catalysts under no-solvent condition.

In this study, we have developed a novel catalyst synthesized by phosphotungstic acid and a gemini quaternary ammonium cation salt. This quaternary ammonium salt not only reduces the interfacial tension between olefins and hydrogen peroxide but also forms a notably stable structure with phosphotungstic acid. Dodecene was successfully epoxidized to epoxy dodecane with a selectivity of 82.9 %. The impact of initial conditions was systematically investigated such as molar ratio, temperature, reaction time, and catalyst dosage on the catalytic performance. Characterization of the catalyst morphology was performed by SEM, TEM and SAXS. Raman spectra, FT-IR and XPS spectra were employed to perform the catalyst transformation during the epoxidation reaction. This catalytic mechanism study could provide the industrial application in the epoxidation of long-chain olefins.

The role of Ginkgo Folium on antitumor: Bioactive constituents and the potential mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. is a well-known and highly regarded resource in Chinese traditional medicine due to its effectiveness and safety. Ginkgo Folium, the leaf of Ginkgo biloba L., contains biologically active constituents with diverse pharmacological activities. Recent studies have shown promising antitumor effects of the bioactive constituents found in Ginkgo Folium against various types of cancer cells, highlighting its potential as a natural source of antitumor agents. Further research is needed to elucidate the underlying mechanisms and optimize its therapeutic potential. AIM OF THE REVIEW: To provide a detailed understanding of the pharmacological activities of Ginkgo Folium and its potential therapeutic benefits for cancer patients. MATERIALS AND METHODS: In this study, we conducted a thorough and systematic search of multiple online databases, including PubMed, Web of Science, Medline, using relevant keywords such as "Ginkgo Folium," "flavonoids," "terpenoids," "Ginkgo Folium extracts," and "antitumor" to cover a broad range of studies that could inform our review. Additionally, we followed a rigorous selection process to ensure that the studies included in our review met the predetermined inclusion criteria. RESULTS: The active constituents of Ginkgo Folium primarily consist of flavonoids and terpenoids, with quercetin, kaempferol, isorhamnetin, ginkgolides, and bilobalide being the major compounds. These active constituents exert their antitumor effects through crucial biological events such as apoptosis, cell cycle arrest, autophagy, and inhibition of invasion and metastasis via modulating diverse signaling pathways. During the process of apoptosis, active constituents primarily exert their effects by modulating the caspase-8 mediated death receptor pathway and caspase-9 mediated mitochondrial pathway via regulating specific signaling pathways. Furthermore, by modulating multiple signaling pathways, active constituents effectively induce G1, G0/G1, G2, and G2/M phase arrest. Among these, the pathways associated with G2/M phase arrest are particularly extensive, with the cyclin-dependent kinases (CDKs) being most involved. Moreover, active constituents primarily mediate autophagy by modulating certain inflammatory factors and stressors, facilitating the fusion stage between autophagosomes and lysosomes. Additionally, through the modulation of specific chemokines and matrix metalloproteinases, active constituents effectively inhibit the processes of epithelial-mesenchymal transition (EMT) and angiogenesis, exerting a significant impact on cellular invasion and migration. Synergistic effects are observed among the active constituents, particularly quercetin and kaempferol. CONCLUSION: Active components derived from Ginkgo Folium demonstrate a comprehensive antitumor effect across various levels and pathways, presenting compelling evidence for their potential in new drug development. However, in order to facilitate their broad and adaptable clinical application, further extensive experimental investigations are required to thoroughly explore their efficacy, safety, and underlying mechanisms of action.

Propionyl-CoA carboxylase subunit B regulates anti-tumor T cells in a pancreatic cancer mouse model.

Most human pancreatic ductal adenocarcinoma (PDAC) are not infiltrated with cytotoxic T cells and are highly resistant to immunotherapy. Over 90% of PDAC have oncogenic KRAS mutations, and phosphoinositide 3-kinases (PI3Ks) are direct effectors of KRAS. Our previous study demonstrated that ablation of Pik3ca in KPC (KrasG12D; Trp53R172H; Pdx1-Cre) pancreatic cancer cells induced host T cells to infiltrate and completely eliminate the tumors in a syngeneic orthotopic implantation mouse model. Now, we show that implantation of Pik3ca-/- KPC (named αKO) cancer cells induces clonal expansion of cytotoxic T cells infiltrating the pancreatic tumors. To identify potential molecules that can regulate the activity of these anti-tumor T cells, we conducted an in vivo genome-wide gene-deletion screen using αKO cells implanted in the mouse pancreas. The result shows that deletion of propionyl-CoA carboxylase subunit B gene (Pccb) in αKO cells (named p-αKO) leads to immune evasion, tumor progression and death of host mice. Surprisingly, p-αKO tumors are still infiltrated with clonally expanded CD8+ T cells but they are inactive against tumor cells. However, blockade of PD-L1/PD1 interaction reactivated these clonally expanded T cells infiltrating p-αKO tumors, leading to slower tumor progression and improve survival of host mice. These results indicate that Pccb can modulate the activity of cytotoxic T cells infiltrating some pancreatic cancers and this understanding may lead to improvement in immunotherapy for this difficult-to-treat cancer.

Botryorhodine J, a new anti-MRSA depsidone isolated from endophytic fungus Alternaria alternata Pas11.

A new depsidone derivative botryorhodine J (1), along with six known compounds (2-7) were obtained from solid rice cultures of Alternaria alternata Pas11 that was isolated from leaves of Phragmites australis. The structure of the new compound was elucidated on the basis of combination of NMR spectroscopic data and high resolution mass spectrometry (HRMS). All the isolated compounds were evaluated for their antibacterial activities against a panel of Gram-positive bacterial strains (methicillin-resistant Staphylococcus aureus [MRSA], Bacillus subtilis and S. aureus). Compounds 1 and 6 displayed antibacterial activity against the three bacterial strains with the minimum inhibitory concentration values (MICs) of 14 - 32 µg/mL, while compound 5 showed good antibacterial activity against above bacterial strains with MIC values of 5 - 8 µg/mL.

Electrochemical detection of oxytetracycline employing sugarcane carbon modified graphite electrode.

The present study used CeO2-Co3O4 quantum dots@porous carbon/multiwalled carbon nanotube (CeO2-Co3O4 QDs@PC/MWCNT/GE) composites to modify graphite electrodes to fabricate high-sensitivity electrochemical sensors to detect the presence of oxytetracycline (OTC). The quantum dots were made from waste sugarcane bagasse. The electrochemical analysis demonstrated the superior electrochemical performance of CeO2-Co3O4 QDs@PC/MWCNT/GE, with a peak current density of 1.276 mA/cm2. Electrochemical impedance spectroscopy (EIS) revealed lower impedance values for CeO2-Co3O4 QDs@PC/MWCNT/GE compared to other electrodes, indicating enhanced conductivity. The modified electrode exhibited an enlarged electrochemically active area, with values of 0.602 cm2, almost seven times that of the bare graphite electrode (0.079 cm2). The results showed that the CeO2-Co3O4 QDs@PC/MWCNT/GE had excellent performance for OTC detection, and its linear calibration range was 1.007 × 10-8 to 2.04 × 10-7 M (i.e., 0.005-0.1 ppm) and 1.007 × 10-6 to 1.209 × 10-4 M (i.e., 0.5-60 ppm). The limit of detection and limit of quantification were 1.23 nM (0.61 ppb) and 4.09 nM (2.03 ppb) (S/N = 3), respectively. The electrode demonstrated long-term stability for up to 7 weeks. This method provides a new way to prepare electrochemical sensors for OTC detection.