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1.
Sunvozertinib for patients in China with platinum-pretreated locally advanced or metastatic non-small-cell lung cancer and EGFR exon 20 insertion mutation (WU-KONG6): single-arm, open-label, multicentre, phase 2 trial.
Wang, M, Fan, Y, Sun, M, Wang, Y, Zhao, Y, Jin, B, Hu, Y, Han, Z, Song, X, Liu, A, et al
The Lancet. Respiratory medicine. 2024;(3):217-224
Abstract
BACKGROUND Sunvozertinib is an oral, irreversible, and selective tyrosine kinase inhibitor that has a favourable safety profile and encouraging antitumour activity, as shown in phase 1 studies of patients with heavily pretreated non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutation (exon20ins). We aimed to assess the antitumour efficacy of sunvozertinib in patients with platinum-pretreated locally advanced or metastatic NSCLC with EGFR exon20ins. METHODS WU-KONG6 is a single-group, open-label, multicentre phase 2 trial of sunvozertinib monotherapy, conducted across 37 medical centres in China. We enrolled adult patients with pathologically or cytologically confirmed locally advanced or metastatic NSCLC whose tumour tissue carried an EGFR exon20ins mutation. All patients had received at least one line of previous systemic therapy, with at least one line containing platinum-based chemotherapy. The primary endpoint was objective response rate (ORR), as assessed by the independent review committee. The ORR was defined as the percentage of patients who achieved complete or partial response, confirmed by two separate assessments with at least 4-week time interval, until disease progression or initiation of any new anti-cancer therapy. Enrolled patients received sunvozertinib 300 mg once daily until meeting discontinuation criteria per the protocol. Patients who received at least one dose of treatment and were evaluable for efficacy analysis were included in the primary analysis, and all patients who received at least one dose of treatment were included in the safety analysis. This study is registered with ChinaDrugTrials.org, CTR20211009, and ClinicalTrials.gov, NCT05712902, and efficacy and safety follow-up are ongoing. FINDINGS Between July 19, 2021, and May 6, 2022, 104 patients were enrolled. At data cutoff (Oct 17, 2022), the last enrolled patient had been followed up for about 6 months. Among 97 patients evaluable for efficacy analysis, 59 (61%) patients achieved tumour response, with a confirmed ORR of 61% (95% CI 50-71). All tumour responses were partial responses. Tumour responses were observed irrespective of age, sex, smoking history, EGFR exon20ins subtypes, brain metastasis at baseline, previous lines of therapy, and history of onco-immunotherapy. In total, 19 death events occurred over a median follow-up period of 7·6 months (IQR 6·1-9·4). Sunvozertinib was well tolerated at 300 mg once daily. The most common grade 3 or worse treatment-related adverse events were blood creatine phosphokinase increased (18 [17%] of 104), diarrhoea (eight [8%]), and anaemia (six [6%]). The most common serious treatment-related adverse events were interstitial lung disease (five [5%] of 104), anaemia (three [3%]), vomiting (two [2%]), nausea (two [2%]) and pneumonia (two [2%]). INTERPRETATION In this phase 2 study, sunvozertinib demonstrated antitumour efficacy in patients with platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins, with a manageable safety profile. A multinational randomised, phase 3 study of sunvozertinib versus platinum-doublet chemotherapy in EGFR exon20ins NSCLC is ongoing (NCT05668988). FUNDING Dizal Pharmaceutical.
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2.
Alendronate modulates cytokine responses in healthy young individuals after BCG vaccination.
Bulut, O, Kilic, G, Debisarun, PA, Röring, RJ, Sun, S, Kolkman, M, van Rijssen, E, Ten Oever, J, Koenen, H, Barreiro, L, et al
Immunology letters. 2024;:106851
Abstract
Bacillus Calmette-Guérin (BCG) vaccination induces memory characteristics in innate immune cells and their progenitors, a process called trained immunity mediated by epigenetic and metabolic reprogramming. Cholesterol synthesis plays an amplifying role in trained immunity through mevalonate release. Nitrogen-containing bisphosphonates (N-BPs), such as alendronate, can inhibit cholesterol synthesis. We explored their effects on trained immunity induced by BCG in a placebo-controlled clinical study (NL74082.091.20) in young, healthy individuals. Participants receiving single-dose oral alendronate on the day of BCG vaccination had more neutrophils and plasma cells one month after treatment. Alendronate led to reduced proinflammatory cytokine production by PBMCs stimulated with heterologous bacterial and viral stimuli one month later. Furthermore, the addition of alendronate transcriptionally suppressed multiple immune response pathways in PBMCs upon stimulation. Our findings indicate that N-BPs modulate the long-lasting effects of BCG vaccination on the cytokine production capacity of innate immune cells.
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3.
Structural characteristics, digestion properties, fermentation properties, and biological activities of butyrylated starch: A review.
Zhang, Y, Li, L, Sun, S, Cheng, L, Gu, Z, Hong, Y
Carbohydrate polymers. 2024;:121825
Abstract
Butyrylated starch is produced by the esterification of hydroxyl groups in starch with butyryl groups, which improves the structural diversity of starch and expands its function and biological activity. The paper summarizes the structural properties and digestive properties, fermentation properties, and biological activities of butyrylated starch and describes the conformational relationships generated by the butyryl groups to reveal the underlying mechanisms. The butyryl groups replace the hydroxyl groups in starch and break the hydrogen bonds, which consequently changes the molecular, crystal, and granular structures of starch, while the starch structure also affects the distribution of the butyryl groups. Binding to the butyryl groups gives starch efficacy in resisting digestion, lowering the glycaemic index, releasing butyric acid in the colon, and regulating intestinal flora and metabolites. Relationships between starch structural parameters and butyric acid production and intestinal flora were also concluded to provide guidance for the rational design of butyrylated starch to improve efficacy. Moreover, based on its digestive and fermentation properties, butyrylated starch has exhibited good therapeutic efficacy for intestinal diseases, diabetes, polycystic ovary syndrome, and chronic restraint stress-induced abnormalities. This review provides a valuable reference for butyrylated starch advancement and utilization.
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4.
Emerging Contaminants: An Emerging Risk Factor for Diabetes Mellitus.
Niu, H, Xu, M, Tu, P, Xu, Y, Li, X, Xing, M, Chen, Z, Wang, X, Lou, X, Wu, L, et al
Toxics. 2024;(1)
Abstract
Emerging contaminants have been increasingly recognized as critical determinants in global public health outcomes. However, the intricate relationship between these contaminants and glucose metabolism remains to be fully elucidated. The paucity of comprehensive clinical data, coupled with the need for in-depth mechanistic investigations, underscores the urgency to decipher the precise molecular and cellular pathways through which these contaminants potentially mediate the initiation and progression of diabetes mellitus. A profound understanding of the epidemiological impact of these emerging contaminants, as well as the elucidation of the underlying mechanistic pathways, is indispensable for the formulation of evidence-based policy and preventive interventions. This review systematically aggregates contemporary findings from epidemiological investigations and delves into the mechanistic correlates that tether exposure to emerging contaminants, including endocrine disruptors, perfluorinated compounds, microplastics, and antibiotics, to glycemic dysregulation. A nuanced exploration is undertaken focusing on potential dietary sources and the consequential role of the gut microbiome in their toxic effects. This review endeavors to provide a foundational reference for future investigations into the complex interplay between emerging contaminants and diabetes mellitus.
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5.
The origin of vitamin B12 levels and risk of all-cause, cardiovascular and cancer specific mortality: A systematic review and dose-response meta-analysis.
Liu, K, Yang, Z, Lu, X, Zheng, B, Wu, S, Kang, J, Sun, S, Zhao, J
Archives of gerontology and geriatrics. 2024;:105230
Abstract
BACKGROUND Vitamin B12 is essential to human but the implications of serum vitamin B12 level for mortality in clinical practice remain unclear. We conducted a systematic review and dose-response meta-analysis to quantify the relationship between vitamin B12 levels and the risk of all-cause, cardiovascular, and cancer mortality. METHODS Electronic databases of PubMed, Embase, and the Cochrane Library Central Register of Controlled Trials were searched from inception through May 2023. Two reviewers independently extracted individual study data and evaluated the risk of bias among the studies using the Newcastle‒Ottawa Scale. To examine a potential nonlinear relationship between the vitamin B12 levels and all-cause mortality, we performed a two-stage random effects dose‒response meta-analysis. RESULTS Twenty-two cohort studies (92,346 individuals with 10,704 all-cause deaths) were included. A linear trend dose-response analysis showed that each 100 pmol/L increase in serum vitamin B12 concentration was associated with a 4 % higher risk of all-cause mortality in the general population (adjusted HR 1.04, 95 % confidence interval CI 1.01 to 1.08; n = 8; P non-linearity = 0.11) and a 6 % higher risk for all-cause mortality in older adults (adjusted HR 1.06, 95 % CI 1.01 to 1.13; n = 4; P non-linearity = 0.78). Current evidence was mixed for the association between serum vitamin B12 concentration and cardiovascular mortality and was limited for cancer mortality. The meta-analysis of cohort studies showed a positive association between a high serum vitamin B12 concentration (>600 pmol/L) and all-cause mortality (adjusted HR 1.50, 95 % CI 1.29 to 1.74; n = 10; p < 0.01), CVD mortality (adjusted HR 2.04, 95 % CI 0.99 to 4.19; n = 2; p = 0.02), except cancer mortality (adjusted HR 1.56, 95 % CI 0.82 to 2.95; n = 3). Similarly, serum vitamin B12 concentrations (400-600 pmol/L) were associated with increased all-cause mortality (adjusted HR 1.34, 95 % CI 1.10 to 1.64; n = 9; p < 0.01). CONCLUSIONS Serum vitamin B12 concentration was positively associated with the risk of all-cause mortality, especially among older adults, with a linear increasing trend. These findings suggested the primary cause of elevated level of serum vitamin B12 concentration should be timely identified and effectively managed in clinical practice.
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6.
Lipid-focused dietary education intervention in pregnant women: study protocol for an open-label, parallel, randomised, intervention study addressing adverse pregnancy outcomes in China.
Zhang, Y, Gao, X, Zhu, H, Sun, S, Contento, IR, Koch, PA, Yu, H
BMJ open. 2024;(1):e076911
Abstract
INTRODUCTION The incidence of infants who are large-for-gestational-age (LGA) is on the rise in China, and its detrimental effects on health have received increasing attention. Diet-based interventions have the potential to reduce adverse birth outcomes, particularly in decreasing the occurrence of LGA infants. We aim to evaluate the effect of lipid-focused diet education based on the theories of behaviour change in pregnant women on maternal and offspring outcomes through a randomised controlled trial. METHODS AND ANALYSIS We have designed an open-label, parallel, multicentre randomised controlled trial in collaboration with three hospitals in Beijing, China.Pregnant women will be recruited before reaching 12 weeks of gestation and will be randomised in a 1:1:1 ratio into three arms: (1) online education arm, (2) pregnancy nutrition checklist and 'one-page flyer' arm and (3) routine antenatal education. The primary outcome LGA will be recorded at birth. Demographic information, physical activity, sleep and medical history will be collected through questionnaires and case cards prior to enrolment. Questionnaires will also be used to collect dietary behaviours and psychosocial factors of pregnant women at enrolment, at 24-28 weeks and 34-36 weeks of gestation. Additionally, information on breastfeeding and complementary food supplementation for infants and young children will be obtained through questionnaires. Physical development indicators of children and taste tests will be assessed 3 years after delivery. ETHICS AND DISSEMINATION The study has received ethical approval from the Capital Medical University Ethics Committee and other collaborating study centres. Informed consent will be introduced to pregnant women, and their consent will be obtained. The findings will be reported in relevant national and international academic conferences and peer-reviewed publications. TRIAL REGISTRATION NUMBER ChiCTR2300071126.
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7.
E. coli phage transport in porous media: Response to colloid types and water saturation.
Zhang, W, Li, S, Zhao, K, Chai, J, Wan, B, Qin, Y, Huan, H, Sun, S, Yang, Y, Jat Baloch, MY
The Science of the total environment. 2024;:167635
Abstract
Because of its long survival time, high migration ability and high pathogenicity, the migration of the virus in the subsurface environment deserves in-depth exploration and research. In this study we investigated the migration behavior of E. coli phage (VI) with organic colloids (HA) or inorganic colloids (SiO2) in the saturated or unsaturated bands and compared the differences in their migration mechanisms.The effects of different colloids on the surface characteristics of VI were analyzed according to particle size and zeta potential. Column experiments were conducted to simulate their migration in the subsurface environment. The results show that HA enhances the stability of VI-HA, promotes VI migration and plays a dominant role in its migration process under both saturated and unsaturated conditions. In contrast, SiO2 puts VI-SiO2 in an unstable state and is easily separated in the unsaturated state, thus promoting VI migration. Based on migration experiments, the extent of influence factors on VI migration was quantified and compared. The effect of colloids on VI migration is greater than that of moisture content, where the effect of HA is greater than that of SiO2. This study provides an experimental research idea to determine the dominant factors affecting virus migration, and provides a general direction and theoretical basis for the biological risk assessment of pathogenic microorganisms in complex underground environments, in order to enable the decision makers to make a response in time, accurately, and efficiently.
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8.
Nanosized Prussian blue and its analogs for bioimaging and cancer theranostics.
Wang, P, Sun, S, Bai, G, Zhang, R, Liang, F, Zhang, Y
Acta biomaterialia. 2024;:77-98
Abstract
Prussian blue (PB) nanoparticles (NPs) and Prussian blue analogs (PBAs) can form metal-organic frameworks through the programmable coordination of ferrous ions with cyanide. PB and PBAs represent a burgeoning class of hybrid functional nano-systems with a wide-ranging application spectrum encompassing biomedicine, cancer diagnosis, and therapy. A comprehensive overview of recent advancements is crucial for gaining insights for future research. In this context, we reviewed the synthesis techniques and surface modification strategies employed to tailor the dimensions, morphology, and attributes of PB NPs. Subsequently, we explored advanced biomedical utilities of PB NPs, encompassing photoacoustic imaging, magnetic resonance imaging, ultrasound (US) imaging, and multimodal imaging. In particular, the application of PB NPs-mediated photothermal therapy, photodynamic therapy, and chemodynamic therapy to cancer treatment was reviewed. Based on the literature, we envision an evolving trajectory wherein the future of Prussian blue-driven biological applications converge into an integrated theranostic platform, seamlessly amalgamating bioimaging and cancer therapy. STATEMENT OF SIGNIFICANCE Prussian blue, an FDA-approved coordinative pigment with a centuries-long legacy, has paved the way for Prussian blue nanoparticles (PB NPs), renowned for their remarkable biocompatibility and biosafety. These PB NPs have found their niche in biomedicine, playing crucial roles in both diagnostics and therapeutic applications. The comprehensive review goes beyond PB NP-based cancer therapy. Alongside in-depth coverage of PB NP synthesis and surface modifications, the review delves into their cutting-edge applications in the realm of biomedical imaging, encompassing techniques such as photoacoustic imaging, magnetic resonance imaging, ultrasound imaging, and multimodal imaging.
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9.
Recent insights into the physicochemical properties, bioactivities and their relationship of tea polysaccharides.
Zhang, Z, Sun, L, Chen, R, Li, Q, Lai, X, Wen, S, Cao, J, Lai, Z, Li, Z, Sun, S
Food chemistry. 2024;:137223
Abstract
Tea polysaccharides (TPS) is receiving global concern in past years due to their therapeutic effects in many diseases such as obesity and diabetes. Many publications imply that the unique physicochemical properties and bioactivities of TPS are prerequisites for its use as a biofilm, drug carrier and emulsifier. Despite numerous healthy benefits, studies on the in-deep structure-activity relationship of TPS still not well explored and explained yet. The main reasons for the research limitation are attributed mainly to the unbreakable advanced structural research technology and the formation of TPS conjugates. The present review also summarizes some similar parameters in primary structure of TPS with better bioactivities, discusses the relationships between their physicochemical properties and bioactivities, and suggests that function-specific TPS would be obtained in the future if the links between preparation methods, physicochemical properties and bioactivities of TPS could be well understood and established.
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10.
B Cells Dynamic in Aging and the Implications of Nutritional Regulation.
Yu, Y, Lu, C, Yu, W, Lei, Y, Sun, S, Liu, P, Bai, F, Chen, Y, Chen, J
Nutrients. 2024;(4)
Abstract
Aging negatively affects B cell production, resulting in a decrease in B-1 and B-2 cells and impaired antibody responses. Age-related B cell subsets contribute to inflammation. Investigating age-related alterations in the B-cell pool and developing targeted therapies are crucial for combating autoimmune diseases in the elderly. Additionally, optimal nutrition, including carbohydrates, amino acids, vitamins, and especially lipids, play a vital role in supporting immune function and mitigating the age-related decline in B cell activity. Research on the influence of lipids on B cells shows promise for improving autoimmune diseases. Understanding the aging B-cell pool and considering nutritional interventions can inform strategies for promoting healthy aging and reducing the age-related disease burden.