Steady-State Delivery and Chemical Modification of Food Nutrients to Improve Cancer Intervention Ability.

Cancer is a crucial global health problem, and prevention is an important strategy to reduce the burden of the disease. Daily diet is the key modifiable risk factor for cancer, and an increasing body of evidence suggests that specific nutrients in foods may have a preventive effect against cancer. This review summarizes the current evidence on the role of nutrients from foods in cancer intervention. It discusses the potential mechanisms of action of various dietary components, including phytochemicals, vitamins, minerals, and fiber. The findings of epidemiological and clinical studies on their association with cancer risk are highlighted. The foods are rich in bioactive compounds such as carotenoids, flavonoids, and ω-3 fatty acids, which have been proven to have anticancer properties. The effects of steady-state delivery and chemical modification of these food's bioactive components on anticancer and intervention are summarized. Future research should focus on identifying the specific bioactive compounds in foods responsible for their intervention effects and exploring the potential synergistic effects of combining different nutrients in foods. Dietary interventions that incorporate multiple nutrients and whole foods may hold promise for reducing the risk of cancer and improving overall health.

Chimeric Antigen Cytotoxic Receptors for In Vivo Engineering of Tumor-Targeting NK Cells.

Chimeric Ag receptor (CAR) NK cells are challenging to manufacture and fail to achieve consistent tumor infiltration and sustained cytolytic function in the tumor microenvironment. In vivo engineering of NK cells using mRNA-based CAR delivery may overcome these issues. In this study, we developed an in vivo programming method by designing CARs that leverage the biology of NK cell receptors for cell type-specific expression and function. These CARs were engineered by fusion of a tumor recognition domain with the natural cytotoxic receptor family including NKp30, NKp44, and NKp46. Our results demonstrated that these natural cytotoxic receptor-based CARs can engage endogenous signaling adaptors to effectively activate human NK cells for tumor lysis and cytokine production. Specifically, we discovered that stable expression of an NKp44-based CAR was contingent on the presence of the immune cell-specific signaling adaptor DAP12. This innovative strategy facilitates direct in situ programming of NK cells, enhancing safety and minimizing off-target effects in nontargeted, healthy tissues.

Organic acid and aromatic compounds create distinctive flavor in the blackening process of jujube.

Previous studies demonstrated jujube blackening effectively increased cyclic adenosine phosphate and triterpene acid levels, improving its nutritional value. However, compositional changes during this process require further elucidation. The objective aimed to analyze compositional transformations during this process with SEM, TPA, UPLC-MS, E-nose. Results showed decreased hardness, springiness, and chewiness coupled with increased gumminess over blackening durations. Untargeted omics analysis revealed increases of 2-aminooctadec-8-ene-1,3,4-trioland carbendazim. Targeted organic acid analysis showed initial citric acid accumulation (1481.62 to 1645.78 mg/kg) in the first 24 h, then declines to 1072.96 mg/kg. Meanwhile, oxalic and lactic acids steadily rose, peaking at 96-120 h before slightly decreasing. E-nose analysis implied alterations in organic sulfide aromatics engendered the characteristic flavors. Organic acid fluctuations likely resulted from sugar biotransformation and thermal degradation. These comprehensive analyses demonstrate jujube blackening imparts a rich and unique flavor, providing theoretical support for investigating the mechanisms and products underlying this process.

Unsupervised clustering analysis of comprehensive health status and its influencing factors on women of childbearing age: a cross-sectional study from a province in central China.

BACKGROUND: Most previous studies on women of childbearing age have focused on reproductive health and fertility intentions, and evidence regarding the comprehensive health status of women of childbearing age is limited. This study aimed to comprehensively examine the health status of women of childbearing age through a multi-method and multi-indicator evaluation, analyze the factors that influence their overall health, and provide sound recommendations for the improvement and promotion of healthy behaviors. METHODS: Data on women of childbearing age living in Shanxi Province were collected between September 2021 and January 2022 through online and offline surveys. The k-means algorithm was used to assess health-related patterns in women, and multivariate nonconditional logistic regression was used to assess the influencing factors of women's overall health. RESULTS: In total, 1,258 of 2,925 (43%) participants were classified as having a good health status in all five domains of the three health dimensions: quality of life, mental health, and illness. Multivariate logistic regression showed that education level, gynecological examination status, health status of family members, access to medical treatment, age, cooking preferences, diet, social support, hand washing habits, attitude toward breast cancer prevention, and awareness of reproductive health were significantly associated with different health patterns. CONCLUSIONS: The comprehensive health status of women of childbearing age in Shanxi Province is generally good; however, a large proportion of women with deficiencies in some dimensions remains. Since lifestyle greatly impacts women's health, health education on lifestyle and health-related issues should be strengthened.

Discovery of Selective and Potent Macrocyclic CDK9 Inhibitors for the Treatment of Osimertinib-Resistant Non-Small-Cell Lung Cancer.

Effectiveness of epidermal growth factor receptor (EGFR) inhibitors, including Osimertinib, for treating non-small-cell lung cancer (NSCLC) is limited due to the continuous emergence of drug resistance. Hence, it is urgent to develop new therapeutic approaches. CDK9, a key regulator of RNA transcription, has emerged as a promising target for the development of antitumor drugs due to its crucial role in modulating the levels of antiapoptotic protein Mcl-1. Herein, we present the synthesis, optimization, and evaluation of selective CDK9 inhibitors with a macrocyclic scaffold that effectively suppresses the growth of NSCLC cells. Notably, compound Z11, a potent CDK9 inhibitor (IC50 = 3.20 nM) with good kinase selectivity, significantly inhibits cell proliferation and colony formation and induces apoptosis in Osimertinib-resistant H1975 cells. Furthermore, Z11 demonstrates a significant suppression of tumor growth in six patient-derived organoids, including three organoids resistant to Osimertinib. Overall, Z11 served as a promising macrocycle-based CDK9 inhibitor for treating Osimertinib-resistant NSCLC.

Discovery of novel flavonoid-based CDK9 degraders for prostate cancer treatment via a PROTAC strategy.

CDK9 plays a vital role in regulating RNA transcription and significantly impacts the expression of short-lived proteins such as Mcl-1 and c-Myc. Thus, targeting CDK9 holds great promise for the development of antitumor drugs. Natural flavonoid derivatives have recently gained considerable attention in the field of antitumor drug research due to their broad bioactivity and low toxicity. In this study, the PROTAC strategy was used to perform structural modifications of the flavonoid derivative LWT-111 to design a series of flavonoid-based CDK9 degraders. Notably, compound CP-07 emerged as a potent CDK9 degrader, effectively suppressing the proliferation and colony formation of 22RV1 cells by downregulating Mcl-1 and c-Myc. Moreover, CP-07 exhibited significant tumor growth inhibition with a TGI of 75.1% when administered at a dose of 20 mg/kg in the 22RV1 xenograft tumor model. These findings demonstrated the potential of CP-07 as a powerful flavonoid-based CDK9 degrader for prostate cancer therapy.

Selection of regioselective DNA aptamer for detection of homocysteine in nondeproteinized human plasma.

Small molecule-binding aptamers often suffer from high cross reactivity to structure analogues in biological samples, limiting their value for clinical diagnosis. Herein, we present a method to overcome this issue, by performing binding-inhibited organic reaction-based regioselective selection of aptamers against homocysteine (Hcy), which is a marker for diagnosing many disorders including stroke and Alzheimer's. This approach has led to isolation of a DNA aptamer that binds to the alkane thiol chain of Hcy with exceptional specificity against cysteine. It also binds with oxidized Hcy at weaker affinity. Using this new aptamer, we produced a reusable fluorescent optical fiber aptasensor for direct and validated detection of both free and total Hcy in nondeproteinized patient plasma in the diagnostic concentration range. The binding site-specific aptamer selection and optical-fiber-sensing strategy can expand the practical utility of aptamers in clinical diagnosis.

Bacterial outer membrane vesicles in cancer: Biogenesis, pathogenesis, and clinical application.

Outer membrane vesicles (OMVs) are spherical, nano-sized particles of bilayer lipid structure secreted by Gram-negative bacteria. They contain a series of cargos from bacteria and are important messengers for communication between bacteria and their environment. OMVs play multiple roles in bacterial survival and adaptation and can affect host physiological functions and disease development by acting on host cell membranes and altering host cell signaling pathways. This paper summarizes the mechanisms of OMV genesis and the multiple roles of OMVs in the tumor microenvironment. Also, this paper discusses the prospects of OMVs for a wide range of applications in drug delivery, tumor diagnosis, and therapy.

Concerns related to the interactions between COVID-19 vaccination and cancer/cancer treatment were barriers to complete primary vaccination series among Chinese cancer patients: A multicentre cross-sectional survey.

COVID-19 vaccination is effective for cancer patients without safety concerns. However, COVID-19 vaccination hesitancy is common among cancer patients. This study investigated factors affecting primary COVID-19 vaccination series completion rate among cancer patients in China. A multicentre cross-sectional study was conducted in four Chinese cities in different geographic regions between May and June 2022. A total of 893 cancer inpatients provided written informed consent and completed the study. Logistic regression models were fitted. Among the participants, 58.8% completed the primary COVID-19 vaccination series. After adjusting for background characteristics, concerns about interactions between COVID-19 vaccination and cancers/cancer treatment (adjusted odds ratios [AOR]: 0.97, 95%CI: 0.94, 0.99) were associated with lower completion of primary vaccination series. In addition, perceived higher risk of COVID-19 infection comparing to people without cancers (AOR: 0.46, 95%CI: 0.24, 0.88), perceived a high chance of having severe consequences of COVID-19 infection (AOR: 0.68, 95%CI: 0.51, 0.91) were also associated with lower completion rate. Being suggested by significant others (AOR: 1.32, 95%CI: 1.23, 1.41) and perceived higher self-efficacy to receive COVID-19 vaccination (AOR: 1.48, 95%CI: 1.31, 1.67) were positively associated with the dependent variable. Completion rate of primary COVID-19 vaccination series was low among Chinese cancer patients. Given the large population size and their vulnerability, this group urgently needs to increase COVID-19 vaccination coverage. Removing concerns about interactions between COVID-19 vaccination and cancers, using fear appeal approach, involving significant others, and facilitating patients to make a plan to receive COVID-19 vaccination might be useful strategies.

Hesitancy to Receive the Booster Doses of COVID-19 Vaccine Among Cancer Patients in China: A Multicenter Cross-Sectional Survey - Four PLADs, China, 2022.

What is already known about this topic?: Cancer patients are more vulnerable and have higher mortality rates from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population; however, coverage for booster doses of the coronavirus disease 2019 (COVID-19) vaccine was low among cancer patients in China. What is added by this report?: Overall, 32.0% and 56.4% of cancer patients from four Provincial Level Administrative Divisions (PLADs) expressed hesitancy toward the first and second booster doses, respectively. Factors negatively associated with hesitancy to receive booster doses included positive attitudes, perceived support, and higher exposure to COVID-19 vaccination information. Conversely, postvaccination fatigue was positively associated with vaccine hesitancy. What are the implications for public health practice?: Improved COVID-19 vaccination coverage is needed to promote health for cancer patients.

The prevalence and burden of four major chronic diseases in the Shanxi Province of Northern China.

Background: Chronic non-communicable diseases constitute an important public health problem that is closely related to behavioral risk factors. The study examined the prevalence, burden, and behavioral risk factors relevant to four major chronic diseases in Shanxi Province, China. The results obtained could provide a basis for the formulation of chronic disease prevention and control strategies in north China. Methods: A multi-stage random sampling method was used to select 14,137 residents aged ≥15 years who completed a questionnaire survey and physical examination. The disease burden was evaluated using the disability-adjusted life years (DALY) index. The extent of disease burden attributable to smoking and drinking behavior was analyzed using counterfactual analysis. Results: The total DALYs due to the four major chronic diseases was 938,100. The years of life lost due to stroke accounted for 74.86%; the years of life lived with disabilities accounted for 54.0 and 68.1% of the total disease burden of coronary heart disease and diabetes. Coronary heart disease attributed to smoking (105,600) was the highest, followed by stroke (77,200), hypertension (6,000), and diabetes mellitus (5,900). Stroke attributed to drinking (30,700) was the highest followed by coronary heart disease (16,700) and diabetes (1,100). The disease burden caused by smoking and drinking was higher in men (164,000 and 40,700, respectively) than in women (30,700 and 7,300, respectively). Conclusion: There is a high prevalence and significant burden associated with major chronic diseases in Shanxi Province. Therefore, the need for the application of various interventions to control smoking and drinking (the major predisposing factors) should be applied to reduce this burden.

Identifying Excessive Intake of Oil and Salt to Prevent and Control Hypertension: A Latent Class Analysis.

Introduction: To identify health hazard behaviors and provide a basis for targeted management and intervention for patients with hypertension, we classified their health-related behaviors. Methods: A multi-stage random sampling method was used to conduct an on-site questionnaire survey among residents aged ≥15 years in a certain urban area of Taiyuan City, Shanxi Province, China. A latent class analysis was used to classify the lifestyle behaviors of patients with hypertension. The lifestyle behavior characteristics of different types of patients with hypertension and their awareness of hypertension were assessed. Results: The prevalence of hypertension in Taiyuan City was 19.5%. Patients with hypertension were classified into three clusters according to their lifestyle patterns: smoking and drinking (13.35%), excessive edible oil and salt intake (68.27%), and healthy behavior (18.38%). Comparing the three latent classes of lifestyle, the distribution of age, sex, marital status, and education level was different (P < 0.05). The awareness of hypertension and the rate of control among the three classes were also different (P < 0.05). Conclusion: The lifestyle behaviors of patients with hypertension have evident classification characteristics. Approximately two-thirds of the patients with hypertension have an excessive intake of oil and salt. Therefore, targeted and precise intervention measures should be taken to control the intake of oil and salt in this cohort.

Gastroprotective activity of polysaccharide from the fruiting body of Hericium erinaceus against acetic acid-induced gastric ulcer in rats and structure of one bioactive fraction.

This study aimed at investigating gastroprotective activity of Hericium erinaceus polysaccharide (HEP) and characterizing one of its bioactive fractions. Acetic acid-induced gastric ulcer (GU) rat model was used to evaluate the gastroprotective activity of HEP, while H2O2-induced injury GES-1 cell model was conducted to screen the bioactive fractions from HEP. Moreover, one of the bioactive fractions was characterized using methylation and 1D/2D NMR analysis. Results indicated HEP treatment could ameliorate acetic acid-induced GU in rats. HEP supplement decreased levels of interleukin-6, tumor necrosis factor-α and malondialdehyde and myeloperoxidase activity, and increased releases of nitric oxide, prostaglandin E2, epidermal growth factor, vascular endothelial growth factor and basic fibroblast growth factor and superoxide dismutase activity in gastric tissues of ulcerated rats. Five purified polysaccharides from HEP were screened to be bioactive fractions with cytoprotection on H2O2-induced injury in GES-1 cells. Among them, RP-S was characterized to be a (1 â†’ 6)-ß-D-glucan, whose backbone was composed of →6)-ß-D-Glcp-(1 â†’ residue and branched with T-ß-D-Glcp-(1 â†’ residue at O-3 position. In conclusion, HEP possessed gastroprotection against acetic acid-induced GU in rats and one of its bioactive fractions was a ß-D-glucan. This study supports the utilization of HEP in anti-GU and provides evidences for the structure of gastroprotective HEP.

Assembly and comparative analysis of the first complete mitochondrial genome of Acer truncatum Bunge: a woody oil-tree species producing nervonic acid.

BACKGROUND: Acer truncatum (purpleblow maple) is a woody tree species that produces seeds with high levels of valuable fatty acids (especially nervonic acid). The species is admired as a landscape plant with high developmental prospects and scientific research value. The A. truncatum chloroplast genome has recently been reported; however, the mitochondrial genome (mitogenome) is still unexplored. RESULTS: We characterized the A. truncatum mitogenome, which was assembled using reads from PacBio and Illumina sequencing platforms, performed a comparative analysis against different species of Acer. The circular mitogenome of A. truncatum has a length of 791,052 bp, with a base composition of 27.11% A, 27.21% T, 22.79% G, and 22.89% C. The A. truncatum mitogenome contains 62 genes, including 35 protein-coding genes, 23 tRNA genes and 4 rRNA genes. We also examined codon usage, sequence repeats, RNA editing and selective pressure in the A. truncatum mitogenome. To determine the evolutionary and taxonomic status of A. truncatum, we conducted a phylogenetic analysis based on the mitogenomes of A. truncatum and 25 other taxa. In addition, the gene migration from chloroplast and nuclear genomes to the mitogenome were analyzed. Finally, we developed a novel NAD1 intron indel marker for distinguishing several Acer species. CONCLUSIONS: In this study, we assembled and annotated the mitogenome of A. truncatum, a woody oil-tree species producing nervonic acid. The results of our analyses provide comprehensive information on the A. truncatum mitogenome, which would facilitate evolutionary research and molecular barcoding in Acer.

Effect of Very Advanced Maternal Age on Pregnant Women and Fetuses.

OBJECTIVE: To compare the difference in the effect on pregnant women and fetuses between very advanced maternal age (age of or over 45 years) and other ages (age below 45 years). STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Changyi People's Hospital, China, from June 2017 and September 2020. METHODOLOGY: Four-hundred singleton pregnancies were selected. One hundred and three pregnant women at age of or over 45 years (Group A) and 297 pregnant women at age below 45 years (Group B) were grouped by age. Serum total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C), incidence of pregnancy complications and fetal outcomes were compared. RESULT: Group A had higher TC and HDL-C than Group B at 12-week, 32-week pregnancy and 3 days after delivery (all p <0.001); Group A had higher TG than Group B at 12-week, 32-week pregnancy and 3 days after delivery (p=0.003, p <0.001 and p <0.001), respectively. Group A had higher incidence of gestational diabetes mellitus (GDM), pregnancy complicated with leiomyoma, gestational hypertension, placenta previa, placental abruption, anemia and postpartum hemorrhage than Group B (all p <0.001). Group A had higher incidence of fetal distress and preterm birth than Group B (both p <0.001). The difference in fetal weight and Apgar score of 5-min infants compared between the two groups was significant (both p<0.001). CONCLUSION: The incidence of gestational complications and adverse perinatal outcomes may be increased in very advanced maternal age singleton pregnant women aged over 45 years. Key Words: Very advanced maternal age, Pregnant women, Pregnancy, Fetus, Complications.

Multi-Layered, Corona Charged Melt Blown Nonwovens as High Performance PM0.3 Air Filters.

Particulate matter (PM) and airborne viruses bring adverse influence on human health. As the most feasible way to prevent inhalation of these pollutants, face masks with excellent filtration efficiency and low press drop are in urgent demand. In this study, we report a novel methodology for producing high performance air filter by combining melt blown technique with corona charging treatment. Changing the crystal structure of polypropylene by adding magnesium stearate can avoid charge escape and ensure the stability of filtration performances. Particularly, the influence of fiber diameter, pore size, porosity, and charge storage on the filtration performances of the filter are thoroughly investigated. The filtration performances of the materials, including the loading test performance are also studied. The melt blown materials formed by four layers presented a significant filtration efficiency of 97.96%, a low pressure drop of 84.28 Pa, and a high quality factor (QF) of 0.046 Pa-1 for paraffin oil aerosol particles. Meanwhile, a robust filtration efficiency of 99.03%, a low pressure drop of 82.32 Pa, and an excellent QF of 0.056 Pa-1 for NaCl aerosol particles could be easily achieved. The multi-layered melt blown filtration material developed here would be potentially applied in the field of protective masks.

A randomized, double-blind, placebo-controlled study of B-cell lymphoma 2 homology 3 mimetic gossypol combined with docetaxel and cisplatin for advanced non-small cell lung cancer with high expression of apurinic/apyrimidinic endonuclease 1.

Background Overexpression of apurinic/apyrimidinic endonuclease 1 (APE1) is an important cause of poor chemotherapeutic efficacy in advanced non-small cell lung cancer (NSCLC) patients. Gossypol, a new inhibitor of APE1, in combination with docetaxel and cisplatin is believed to improve the efficacy of chemotherapy for advanced NSCLC with high APE1 expression. Methods Sixty-two patients were randomly assigned to two groups. Thirty-one patients in the experimental group received 75 mg/m2 docetaxel and 75 mg/m2 cisplatin on day 1 with gossypol administered at 20 mg once daily on days 1 to 14 every 21 days. The control group received placebo with the same docetaxel and cisplatin regimen. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), response rate, and toxicity. Results There were no significant differences in PFS and OS between the experimental group and the control group. The median PFS (mPFS) in the experimental and control groups was 7.43 and 4.9 months, respectively (HR = 0.54; p = 0.06), and the median OS (mOS) was 18.37 and 14.7 months, respectively (HR = 0.68; p = 0.27). No significant differences in response rate and serious adverse events were found between the groups. Conclusion The experimental group had a better mPFS and mOS than did the control group, though no significant difference was observed. Because the regimen of gossypol combined with docetaxel and cisplatin was well tolerated, future studies with larger sample sizes should be performed.