Type 3 resistant starch from Canna edulis reduce lipid levels in patients with mild hyperlipidemia through altering gut microbiome: A double- blind randomized controlled trial.

Type 3 resistant starch from Canna edulis (Ce-RS3) is an insoluble dietary fiber which could improve blood lipids in animals, but clinically robust evidence is still lacking. We performed a double-blind randomized controlled trial to assess the effects of Ce-RS3 on lipids in mild hyperlipidemia. One hundred and fifteen patients were included followed the recruitment criteria, and were randomly allocated to receive Ce-RS3 or placebo (native starch from Canna edulis) for 12 weeks (20 g/day). In addition to serum lipids, complete blood counts, serum inflammatory factors, antioxidant indexes, and dietary survey, 16 S rRNA sequencing technique was utilized to analyze the gut microbiota alterations. Targeted quantitative metabolomics (TQM) was used to detect metabolite changes. Compared with the placebo, Ce- RS3 significantly decreased levels of total cholesterol, lowdensity lipoprotein cholesterol, and non-high-density lipoprotein cholesterol, and increased the glutathione peroxidase. Based on the 16 S rRNA sequencing, TQM, the correlation analysis, as well as the Kyoto Encyclopedia of Genes (KEGG) and Genomes and Human Metabolome Database (HMDB) analysis, we found that Ce-RS3 could increase the abundances of genera Faecalibacterium and Agathobacter, while reduce the abundances of genera norank_f_Ruminococcaceae and Christensenellaceae_R-7_ group to regulate phenylalanine metabolism, which could reduce the fatty acid biosynthesis and fatty acid elongation in the mitochondria to lower blood lipids. Conclusively, we firstly confirmed the feasibility of Ce-RS3 for clinical application, which presents a novel, effective therapy for the mild hyperlipidemia. (Chictr. org. cn. Clinical study on anti-mild hyperlipidemia of Canna edulis RS3 resistant starch, ID Number: ChiCTR2200062871).

Multiplex Asymmetric PCR by Combining the Amplification Refractory Mutation System with the Homo-Tag-Assisted Nondimer System.

Asymmetric PCR is widely used to produce single-stranded amplicons (ss-amplicons) for various downstream applications. However, conventional asymmetric PCR schemes are susceptible to events that affect primer availability, which can be exacerbated by multiplex amplification. In this study, a new multiplex asymmetric PCR approach that combines the amplification refractory mutation system (ARMS) with the homo-Tag-assisted nondimer system (HANDS) is described. ARMS-HANDS (A-H) PCR utilizes equimolar-tailed forward and reverse primers and an excess Tag primer. The tailed primer pairs initiate exponential symmetric amplification, whereas the Tag primer drives linear asymmetric amplification along fully matched strands but not one-nucleotide mismatched strands, thereby generating excess ss-amplicons. The production of ss-amplicons is validated using agarose gel electrophoresis, sequencing, and melting curve analysis. Primer dimer alleviation is confirmed by both the reduced Loss function value and a 20-fold higher sensitivity in an 11-plex A-H PCR assay than in an 11-plex conventional asymmetric PCR assay. Moreover, A-H PCR demonstrates unbiased amplification by its allele quantitative ability in correct identification of all 31 trisomy 21 samples among 342 clinical samples. A-H PCR is a new generation of multiplex asymmetric amplification approach with various applications, especially when sensitive and quantitative detection is required.

Solobacterium moorei promotes the progression of adenomatous polyps by causing inflammation and disrupting the intestinal barrier.

BACKGROUND: Adenomatous polyps (APs) with inflammation are risk factors for colorectal cancer. However, the role of inflammation-related gut microbiota in promoting the progression of APs is unknown. METHODS: Sequencing of the 16S rRNA gene was conducted to identify characteristic bacteria in AP tissues and normal mucosa. Then, the roles of inflammation-related bacteria were clarified by Spearman correlation analysis. Furthermore, colorectal HT-29 cells, normal colon NCM460 cells, and azoxymethane-treated mice were used to investigate the effects of the characteristic bacteria on progression of APs. RESULTS: The expression levels of inflammation-related markers (diamine oxidase, D-lactate, C-reactive protein, tumor necrosis factor-α, interleukin-6 and interleukin-1ß) were increased, whereas the expression levels of anti-inflammatory factors (interleukin-4 and interleukin-10) were significantly decreased in AP patients as compared to healthy controls. Solobacterium moorei (S. moorei) was enriched in AP tissues and fecal samples, and significantly positively correlated with serum inflammation-related markers. In vitro, S. moorei preferentially attached to HT-29 cells and stimulated cell proliferation and production of pro-inflammatory factors. In vivo, the incidence of intestinal dysplasia was significantly increased in the S. moorei group. Gavage of mice with S. moorei upregulated production of pro-inflammatory factors, suppressed proliferation of CD4+ and CD8+cells, and disrupted the integrity of the intestinal barrier, thereby accelerating progression of APs. CONCLUSIONS: S. moorei accelerated the progression of AP in mice via activation of the NF-κB signaling pathway, chronic low-grade inflammation, and intestinal barrier disruption. Targeted reduction of S. moorei presents a potential strategy to prevent the progression of APs.

Efficacy of Bifidobacterium animalis subsp. lactis BL-99 in the treatment of functional dyspepsia: a randomized placebo-controlled clinical trial.

Current treatment for functional dyspepsia (FD) has limited and unsustainable efficacy. Probiotics have the sustainable potential to alleviate FD. This randomized controlled clinical trial (Chinese Clinical Trial Registry, ChiCTR2000041430) assigned 200 FD patients to receive placebo, positive-drug (rabeprazole), or Bifidobacterium animalis subsp. lactis BL-99 (BL-99; low, high doses) for 8-week. The primary outcome was the clinical response rate (CRR) of FD score after 8-week treatment. The secondary outcomes were CRR of FD score at other periods, and PDS, EPS, serum indicators, fecal microbiota and metabolites. The CRR in FD score for the BL-99_high group [45 (90.0%)] was significantly higher than that for placebo [29 (58.0%), p = 0.001], BL-99_low [37 (74.0%), p = 0.044] and positive_control [35 (70.0%), p = 0.017] groups after 8-week treatment. This effect was sustained until 2-week after treatment but disappeared 8-week after treatment. Further metagenomic and metabolomics revealed that BL-99 promoted the accumulation of SCFA-producing microbiota and the increase of SCFA levels in stool and serum, which may account for the increase of serum gastrin level. This study supports the potential use of BL-99 for the treatment of FD.

Zonisamide attenuates pressure overload-induced myocardial hypertrophy in mice through proteasome inhibition.

Myocardial hypertrophy is a pathological thickening of the myocardium which ultimately results in heart failure. We previously reported that zonisamide, an antiepileptic drug, attenuated pressure overload-caused myocardial hypertrophy and diabetic cardiomyopathy in murine models. In addition, we have found that the inhibition of proteasome activates glycogen synthesis kinase 3 (GSK-3) thus alleviates myocardial hypertrophy, which is an important anti-hypertrophic strategy. In this study, we investigated whether zonisamide prevented pressure overload-caused myocardial hypertrophy through suppressing proteasome. Pressure overload-caused myocardial hypertrophy was induced in mice by trans-aortic constriction (TAC) surgery. Two days after the surgery, the mice were administered zonisamide (10, 20, 40 mg·kg-1·d-1, i.g.) for four weeks. We showed that zonisamide administration significantly mitigated impaired cardiac function. Furthermore, zonisamide administration significantly inhibited proteasome activity as well as the expression levels of proteasome subunit beta types (PSMB) of the 20 S proteasome (PSMB1, PSMB2 and PSMB5) and proteasome-regulated particles (RPT) of the 19 S proteasome (RPT1, RPT4) in heart tissues of TAC mice. In primary neonatal rat cardiomyocytes (NRCMs), zonisamide (0.3 µM) prevented myocardial hypertrophy triggered by angiotensin II (Ang II), and significantly inhibited proteasome activity, proteasome subunits and proteasome-regulated particles. In Ang II-treated NRCMs, we found that 18α-glycyrrhetinic acid (18α-GA, 2 mg/ml), a proteasome inducer, eliminated the protective effects of zonisamide against myocardial hypertrophy and proteasome. Moreover, zonisamide treatment activated GSK-3 through inhibiting the phosphorylated AKT (protein kinase B, PKB) and phosphorylated liver kinase B1/AMP-activated protein kinase (LKB1/AMPKα), the upstream of GSK-3. Zonisamide treatment also inhibited GSK-3's downstream signaling proteins, including extracellular signal-regulated kinase (ERK) and GATA binding protein 4 (GATA4), both being the hypertrophic factors. Collectively, this study highlights the potential of zonisamide as a new therapeutic agent for myocardial hypertrophy, as it shows potent anti-hypertrophic potential through the suppression of proteasome.

Improving the Laser-Induced Breakdown Spectroscopy for Highly Efficient Trace Measurement of Hazardous Components in Waste Oils.

Improper disposal of waste oils containing hazardous components damages the environment and the ecosystem, posing a significant threat to human life and health. Here, we present a method of discharge-assisted laser-induced breakdown spectroscopy combined with filter paper sampling (DA-LIBS-FPS) to detect hazardous components and trace the source of polluting elements. DA-LIBS-FPS significantly enhances spectral intensity by 1-2 orders of magnitude due to the discharge energy deposition into the laser-induced plasma and the highly efficient laser-sample interaction on the filter paper, when compared to single-pulse LIBS with silica wafer sampling (SP-LIBS-SWS). Additionally, the signal-to-noise ratio and the signal-to-background ratio are both significantly increased. Resultantly, indiscernible lines, such as CN and Cr I, are well distinguished. In contrast with DA-LIBS combined with silica wafer sampling (DA-LIBS-SWS), the spectral signal fluctuations in DA-LIBS-FPS are reduced by up to 33%, because of the homogeneous distribution of the oil layer on the filter paper in FPS. Further examination indicates that the limit of detection for Ba is reduced from a several parts per million level in SP-LIBS-SWS to a dozens of parts per billion level in DA-LIBS-FPS, i.e., nearly 2 orders of magnitude enhancement in analysis sensitivity. This improvement is attributed to the extended plasma lifespan in DA-LIBS and the increasing electron density and plasma temperature in FPS. DA-LIBS-FPS provides a low-cost, handy, rapid, and highly sensitive avenue to analyze the hazardous components in waste oils with great potential in environmental and ecological monitoring.

Analysis of Airway Thickening and Serum Cytokines in COPD Patients with Frequent Exacerbations: A Heart of the Matter.

Background: Differences in lung function for Chronic Obstructive Pulmonary Disease (COPD) cause bias in the findings when identifying frequent exacerbator phenotype-related causes. The aim of this study was to determine whether computed tomographic (CT) biomarkers and circulating inflammatory biomarkers were associated with the COPD frequent exacerbator phenotype after eliminating the differences in lung function between a frequent exacerbator (FE) group and a non-frequent exacerbator (NFE) group. Methods: A total of 212 patients with stable COPD were divided into a FE group (n=106) and a NFE group (n=106) according to their exacerbation history. These patients were assessed by spirometry, quantitative CT measurements and blood sample measurements during their stable phase. Univariate and multivariate logistic regression were used to assess the association between airway thickening or serum cytokines and the COPD frequent exacerbator phenotype. Receiver operating characteristic (ROC) curves were calculated for Pi10, WA%, IL-1ß and IL-4 to identify frequent exacerbators. Results: Compared with NFE group, FE group had a greater inner perimeter wall thickness of a 10 mm diameter bronchiole (Pi10), a greater airway wall area percentage (WA%) and higher concentrations of IL-1ß and IL-4 (p<0.001). After adjusting for sex, age, BMI, FEV1%pred and smoking pack-years, Pi10, WA%, IL-ß and IL-4 were independently associated with a frequent exacerbator phenotype (p<0.001). Additionally, there was an increase in the odds ratio of the frequent exacerbator phenotype with increasing Pi10, WA%, IL-4, and IL-1ß (p for trend <0.001). The ROC curve demonstrated that IL-1ß had a significantly larger calculated area under the curve (p < 0.05) than Pi10, WA% and IL-4. Conclusion: Pi10, WA%, IL-4, and IL-1ß were independently associated with the frequent exacerbator phenotype among patients with stable COPD, suggesting that chronic airway and systemic inflammation contribute to the frequent exacerbator phenotype. Trial Registration: This trial was registered in Chinese Clinical Trial Registry (https://www.chictr.org.cn). Its registration number is ChiCTR2000038700, and date of registration is September 29, 2020.

Red Emission Carbon Nanoparticles Which Can Simultaneously Responding to Hypochlorite and pH.

Multi-targets detection has obtained much attention because this sensing mode can realize the detection of multi-targets simultaneously, which is helpful for biomedical analysis. Carbon nanoparticles have attracted extensive attention due to their superior optical and chemical properties, but there are few reports about red emission carbon nanoparticles for simultaneous detection of multi-targets. In this paper, a red emission fluorescent carbon nanoparticles were prepared by 1, 2, 4-triaminobenzene dihydrochloride at room temperature. The as-prepared red emission fluorescent carbon nanoparticles exhibited strong emission peak located at 635 nm with an absolute quantum yield up to 24%. They showed excellent solubility, high photostability and good biocompatibility. Furthermore, it could sensitively and selectively response to hypochlorite and pH, thus simultaneous detection of hypochlorite and pH was achieved by combining the red emission fluorescent carbon nanoparticles with computational chemistry. The formation mechanisms of red emission fluorescent carbon nanoparticles and their response to hypochlorite and pH were investigated, respectively.

Subchronic feeding study of glyphosate-tolerant maize GG2 with the gr79-epsps and gat genes in Wistar Han RCC rats.

The genetically modified (GM) maize GG2 contains gr79-epsps and gat genes, conferring glyphosate tolerance. The present study aimed to investigate potential effects of maize GG2 in a 90-day subchronic feeding study on Wistar Han RCC rats. Maize grains from GG2 or non-GM maize were incorporated into diets at concentrations of 25% and 50% and administered to Wistar Han RCC rats (n = 10/sex/group) for 90 days. The basal-diet group of rats (n = 10/sex/group) were fed with common commercialized rodent diet. Compared with rats fed with the corresponding non-GM maize and the basal-diet, no biologically relevant differences were observed in rats fed with the maize GG2, according to the results of body weight/gain, feed consumption/utilization, clinical signs, mortality, ophthalmology, clinical pathology (hematology, prothrombin time, urinalysis, serum chemistry), organ weights, and gross and microscopic pathology. Under the conditions of this study, these results indicated that maize GG2 is as safe as the non-GM maize in this 90-day feeding study.

Alteration of the large-scale white-matter functional networks in autism spectrum disorder.

Autism spectrum disorder is a neurodevelopmental disorder whose core deficit is social dysfunction. Previous studies have indicated that structural changes in white matter are associated with autism spectrum disorder. However, few studies have explored the alteration of the large-scale white-matter functional networks in autism spectrum disorder. Here, we identified ten white-matter functional networks on resting-state functional magnetic resonance imaging data using the K-means clustering algorithm. Compared with the white matter and white-matter functional network connectivity of the healthy controls group, we found significantly decreased white matter and white-matter functional network connectivity mainly located within the Occipital network, Middle temporo-frontal network, and Deep network in autism spectrum disorder. Compared with healthy controls, findings from white-matter gray-matter functional network connectivity showed the decreased white-matter gray-matter functional network connectivity mainly distributing in the Occipital network and Deep network. Moreover, we compared the spontaneous activity of white-matter functional networks between the two groups. We found that the spontaneous activity of Middle temporo-frontal and Deep network was significantly decreased in autism spectrum disorder. Finally, the correlation analysis showed that the white matter and white-matter functional network connectivity between the Middle temporo-frontal network and others networks and the spontaneous activity of the Deep network were significantly correlated with the Social Responsiveness Scale scores of autism spectrum disorder. Together, our findings indicate that changes in the white-matter functional networks are associated behavioral deficits in autism spectrum disorder.

A 90-day feeding study of genetically modified maize LP007-1 in wistar han RCC rats.

LP007-1 is a variety of insect-resistant and herbicide-tolerant maize containing the modified cry1Ab, cry2Ab, vip3Aa and cp4-epsps genes. The food safety assessment of the maize LP007-1 was conducted in Wistar Han RCC rats by a 90-days feeding study. Maize grains from both LP007-1 or its corresponding non-genetically modified control maize AX808 were incorporated into rodent diets at 25% and 50% concentrations by mass and administered to rats (n = 10/sex/group) for 90 days. A commercialized rodent diet was fed to an additional group as the basal-diet group. The diets of all groups were nutritionally balanced. No biologically relevant differences were observed in rats fed with maize LP007-1 compared to rats fed with AX808 and the basal-diet with respect to body weight/gain, food consumption/utilization, clinical signs, mortality, ophthalmology, clinical pathology (hematology, prothrombin time, activation of partial thrombin time, serum chemistry, urinalysis), organ weights, and gross and microscopic pathology. Considering the circumstances of this study, the results provided evidence that LP007-1 maize did not exhibit toxicity in the 90-day feeding study.

Early-life risk factors for food allergy: Dietary and environmental factors revisited.

There appears a steep increase in the prevalence of food allergy worldwide in the past few decades. It is believed that, rather than genetic factors, the recently altered dietary and environmental factors are the driving forces behind the rapid increase of this disease. Accumulating evidence has implied that external exposures that occurred in prenatal and postnatal periods could affect the development of oral tolerance in later life. Understanding the potential risk factors for food allergy would greatly benefit the progress of intervention and therapy. In this review, we present updated knowledge on the dietary and environmental risk factors in early life that have been shown to impact the development of food allergy. These predominantly include dietary habits, microbial exposures, allergen exposure routes, environmental pollutants, and so on. The key evidence, conflicts, and potential research topics of each theory are discussed, and associated interventional strategies to prevent the disease development and ameliorate treatment burden are included. Accumulating evidence has supported the causative role of certain dietary and environmental factors in the establishment of oral tolerance in early life, especially the time of introducing allergenic foods, skin barrier function, and microbial exposures. In addition to certain immunomodulatory factors, increasing interest is raised toward modern dietary patterns, where adequately powered studies are required to identify contributions of those modifiable risk factors. This review broadens our understanding of the connections between diet, environment, and early-life immunity, thus benefiting the progress of intervention and therapy of food allergy.

Association of eating habits with health perception and diseases among Chinese physicians: a cross-sectional study.

Background: Some eating habits may be related to the development of gastrointestinal diseases, obesity, and related metabolic dysfunctions. Because of long working hours, and shift schedules, physicians are more likely to form such eating habits and have a high risk of developing these diseases. Objectives: We aimed to investigate the association between physicians' eating habits and their health perception and diseases. Methods: Between 24 June and 5 August 2020, we performed convenience sampling of in-service physicians in hospitals in mainland China. A questionnaire was administered to collect data pertaining to basic sociodemographic characteristics, eating habits, health-related information such as body mass index classification, and prevalence of common diseases. The associations among eating habits and perceived suboptimal health status, micronutrient deficiency-related diseases, obesity, and related metabolic diseases were analysed. Results: The prevalence of unhealthy eating habits was high: more eating out-of-home (53.4% in hospital canteens, 23.0% in restaurants and takeaways), fewer meals at home, irregular meals (30.5%), and eating too fast (the duration <10 min, 34.6%). Among those with the above eating habits, the prevalence rates of sub-optimal health and disease were higher than among those without the above eating habits. Conclusion: Eating habits such as frequent eating out-of-home, irregular meals, and eating too fast were common among physicians, and were significantly related to perceived sub-optimal health status and disease occurrence.

Protective effects and molecular mechanisms of tea polyphenols on cardiovascular diseases.

Aging is the most important factor contributing to cardiovascular diseases (CVDs), and the incidence and severity of cardiovascular events tend to increase with age. Currently, CVD is the leading cause of death in the global population. In-depth analysis of the mechanisms and interventions of cardiovascular aging and related diseases is an important basis for achieving healthy aging. Tea polyphenols (TPs) are the general term for the polyhydroxy compounds contained in tea leaves, whose main components are catechins, flavonoids, flavonols, anthocyanins, phenolic acids, condensed phenolic acids and polymeric phenols. Among them, catechins are the main components of TPs. In this article, we provide a detailed review of the classification and composition of teas, as well as an overview of the causes of aging-related CVDs. Then, we focus on ten aspects of the effects of TPs, including anti-hypertension, lipid-lowering effects, anti-oxidation, anti-inflammation, anti-proliferation, anti-angiogenesis, anti-atherosclerosis, recovery of endothelial function, anti-thrombosis, myocardial protective effect, to improve CVDs and the detailed molecular mechanisms.

The contradictory role of branched-chain amino acids in lifespan and insulin resistance.

Branched-chain amino acids (BCAAs; a mixture of leucine, valine and isoleucine) have important regulatory effects on glucose and lipid metabolism, protein synthesis and longevity. Many studies have reported that circulating BCAA levels or dietary intake of BCAAs is associated with longevity, sarcopenia, obesity, and diabetes. Among them, the influence of BCAAs on aging and insulin resistance often present different benefits or harmful effects in the elderly and in animals. Considering the nonobvious correlation between circulating BCAA levels and BCAA uptake, as well as the influence of diseases, diet and aging on the body, some of the contradictory conclusions have been drawn. The regulatory mechanism of the remaining contradictory role may be related to endogenous branched-chain amino acid levels, branched-chain amino acid metabolism and mTOR-related autophagy. Furthermore, the recent discovery that insulin resistance may be independent of longevity has expanded the research thinking related to the regulatory mechanism among the three. However, the negative effects of BCAAs on longevity and insulin resistance were mostly observed in high-fat diet-fed subjects or obese individuals, while the effects in other diseases still need to be studied further. In conclusion, there is still no definite conclusion on the specific conditions under which BCAAs and insulin resistance extend life, shorten life, or do not change lifespan, and there is still no credible and comprehensive explanation for the different effects of BCAAs and insulin resistance on lifespan.

A novel onco-cardiological mouse model of lung cancer-induced cardiac dysfunction and its application in identifying potential roles of tRNA-derived small RNAs.

An increasing body of research suggests cancer-induced cardiovascular diseases, leading to the appearance of an interdisciplinary study known as onco-cardiology. Lung cancer has the highest incidence and mortality. Cardiac dysfunction constitutes a major cause of death in lung cancer patients. However, its mechanism has not been elucidated because suitable animal models that adequately mimic clinical features are lacking. Here, we established a novel chemically induced lung cancer mouse model using benzo[a]pyrene and urethane to recapitulate the general characteristics of cardiac dysfunction caused by lung cancer, the cardiac disorders in the context of the progression of lung cancer were evaluated using echocardiographic and histological approaches. The pathological changes included myocardial ischaemia, pericarditis, cardiac pre-cachexia, and pulmonary artery hypertension. We performed sequencing to detect the tRNA-derived fragments and tRNA-derived stress-induced RNAs (tRFs/tiRNAs) expressions in mouse heart tissue. 22 upregulated and 16 downregulated tRFs/tiRNAs were identified. Subsequently, the top 10 significant results of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were presented. The in vitro model was established by exposing neonatal rat cardiomyocytes and myocardial fibroblasts to lung tumour cell-conditioned medium, respectively. Western blotting revealed significant changes in cardiac failure markers (atrial natriuretic peptide and α-myosin heavy chain) and cardiac fibrosis markers (Collagen-1 and Collagen-3). Our model adequately reflects the pathological features of lung cancer-induced cardiac dysfunction. Furthermore, the altered tRF/tiRNA profiles showed great promise as novel targets for therapies. These results might pave the way for research on therapeutic targets in onco-cardiology.

Cathepsin K-Activated Probe for Fluoro-Photoacoustic Imaging of Early Osteolytic Metastasis.

Precise detection of early osteolytic metastases is crucial for their treatment but remains challenging in the clinic because of the limited sensitivity and specificity of traditional imaging techniques. Although fluorescence imaging offers attractive features for the diagnosis of osteolytic metastases, it is hampered by limited penetration depth. To address this issue, a fluoro-photoacoustic dual-modality imaging probe comprising a near-infrared dye caged by a cathepsin K (CTSK)-cleavable peptide sequence on one side and functionalized with osteophilic alendronate through a polyethylene glycol linker on the other side is reported. Through systematic in vitro and in vivo experiments, it is demonstrated that in response to CTSK, the probe generated both near-infrared fluorescent and photoacoustic signals from bone metastatic regions, thus offering a potential strategy for detecting deep-seated early osteolytic metastases.

Positive Association of Serum Vitamin B6 Levels with Intrapulmonary Lymph Node and/or Localized Pleural Metastases in Non-Small Cell Lung Cancer: A Retrospective Study.

The relationship between vitamin B levels and the development and progression of lung cancer remains inconclusive. We aimed to investigate the relationship between B vitamins and intrapulmonary lymph nodes as well as localized pleural metastases in patients with non-small cell lung cancer (NSCLC). This was a retrospective study including patients who underwent lung surgery for suspected NSCLC at our institution from January 2016 to December 2018. Logistic regression models were used to evaluate the associations between serum B vitamin levels and intrapulmonary lymph node and/or localized pleural metastases. Stratified analysis was performed according to different clinical characteristics and tumor types. A total of 1498 patients were included in the analyses. Serum vitamin B6 levels showed a positive association with intrapulmonary metastasis in a multivariate logistic regression (odds ratio (OR) of 1.016, 95% confidence interval (CI) of 1.002-1.031, p = 0.021). After multivariable adjustment, we found a high risk of intrapulmonary metastasis in patients with high serum vitamin B6 levels (fourth quartile (Q4) vs. Q1, OR of 1.676, 95%CI of 1.092 to 2.574, p = 0.018, p for trend of 0.030). Stratified analyses showed that the positive association between serum vitamin B6 and lymph node metastasis appeared to be stronger in females, current smokers, current drinkers, and those with a family history of cancer, squamous cell carcinoma, a tumor of 1-3 cm in diameter, or a solitary tumor. Even though serum vitamin B6 levels were associated with preoperative NSCLC upstaging, B6 did not qualify as a useful biomarker due to weak association and wide confidence intervals. Thus, it would be appropriate to prospectively investigate the relationship between serum vitamin B6 levels and lung cancer further.

A Tumor-Microenvironment-Activatable Molecular Pro-Theranostic Agent for Photodynamic and Immunotherapy of Cancer.

Cancer-associated fibroblasts (CAFs) are the major components of the tumor-associated matrix and play an important role in tumor progression and immunosuppression. Therefore, precise theranostics of CAFs are beneficial for CAFs-targeted therapies. However, imaging agents enabling precise theranostics of CAFs have been rarely exploited. To tackle this issue, a molecular pro-theranostic probe (FMP) with activatable fluorescence, photoacoustic (PA) imaging, and photodynamic therapy (PDT) is developed in response to fibroblast activation protein α (FAPα) overexpressed in >90% types of CAFs and some tumor cells. Attributed to efficient activatable phototoxicity toward CAFs and tumor cells, together with activated immunogenic cell death (ICD), complete tumor regression of primary tumors and abscopal effect of distant tumors are observed in a 4T1-tumor-bearing mice model. By integration with PD-L1 checkpoint blockade immunotherapy, enhanced systemic immune responses are evoked to obtain long-lasting tumor suppression of both primary and distant tumors as well as arrest systemic cancer metastasis in living mice.