Association between oral microbiome and seven types of cancers in East Asian population: a two-sample Mendelian randomization analysis

Background: The oral microbiome has been intricately linked to various pathological conditions, notably cancer, though clear causal links remain elusive. This study aimed to investigate the potential causal relationships between the oral microbiome and seven major cancers: breast, lung, pancreatic, colorectal, gastric, ovarian, and prostate cancers, leveraging Mendelian randomization (MR).Methods: A two-sample MR analysis was conducted using genome-wide association study (GWAS) data specific to oral microbiota in individuals of East Asian descent. Single nucleotide polymorphisms (SNPs) independent of confounders served as instrumental variables (IVs) to deduce causality. MR methodologies such as the inverse variance weighted (IVW) method, weighted median (WM) method, and Mendelian randomization-Egger (MR-Egger) method were employed. The study utilized datasets encapsulating a multitude of cancer cases and controls, focusing on Asian populations.Results: Our analysis revealed intricate associations between specific bacterial genera of the oral microbiome and diverse cancers. Notably, Fusobacterium showed mixed associations with various cancers, while genera like Prevotella and Streptococcus exhibited nuanced roles across malignancies. The genus Aggregatibacter demonstrated a multifaceted influence, positively correlating with some cancers while inhibiting others.Conclusion: Our findings underscore the profound implications of the oral microbiome in systemic malignancies, suggesting potential modulatory roles in cancer etiology. These insights, though preliminary, accentuate the need for deeper exploration and could pave the way for novel therapeutic strategies

Fault Separation Based on An Excitation Operator with Application to a Quadrotor UAV

This paper presents an excitation operator based fault separation architecture for a quadrotor unmanned aerial vehicle (UAV) subject to loss of effectiveness (LoE) faults, actuator aging, and load uncertainty. The actuator fault dynamics is deeply excavated, containing the deep coupling information among the actuator faults, the system states, and control inputs. By explicitly considering the physical constraints and tracking performance, an excitation operator and corresponding integrated state observer are designed to estimate separately actuator fault and load uncertainty. Moreover, a fault separation maneuver and a safety controller are proposed to ensure the tracking performance when the excitation operator is injected. Both comparative simulation and flight experiments have demonstrated the effectiveness of the proposed scheme while maintaining high levels of tracking performance

Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells

To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (P<0.01). Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells

Individualist–Collectivist Differences in Climate Change Inaction: The Role of Perceived Intractability

The willingness to take action against climate change may be shaped by cultural orientations. The present study investigated individualist–collectivist differences in climate change inaction as well as the mediating role of perceived intractability. In Study 1, a survey of 182 undergraduates showed that greater perceived intractability of climate change was significantly related to a lower frequency of climate-friendly actions in the preceding 6 months. In Study 2, participants who were exposed to information concerning the intractability of climate change (experimental group, n = 98) reported a significantly greater perceived intractability of climate change and lower intention to assume a low-carbon lifestyle than those presented with neutral information (control group, n = 83). Based on Studies 1 and 2, participants with collectivist or individualist orientations were recruited from a pool of Chinese undergraduate students in Study 3. We found that participants with a more individualist orientation (n = 62) are more subject to perceived intractability, and less likely to take climate-friendly action than those with a more collectivist orientation (n = 94), and individualist/collectivist status affects climate change inaction through perceived intractability as mediator. The implications of these findings are discussed in relation to the promotion of public engagement with climate change by mitigating perceived intractability

Acoustic Three-dimensional Chern Insulators with Arbitrary Chern Vectors

The Chern vector is a vectorial generalization of the scalar Chern number, being able to characterize the topological phase of three-dimensional (3D) Chern insulators. Such a vectorial generalization extends the applicability of Chern-type bulk-boundary correspondence from one-dimensional (1D) edge states to two-dimensional (2D) surface states, whose unique features, such as forming nontrivial torus knots or links in the surface Brillouin zone, have been demonstrated recently in 3D photonic crystals. However, since it is still unclear how to achieve an arbitrary Chern vector, so far the surface-state torus knots or links can emerge, not on the surface of a single crystal as in other 3D topological phases, but only along an internal domain wall between two crystals with perpendicular Chern vectors. Here, we extend the 3D Chern insulator phase to acoustic crystals for sound waves, and propose a scheme to construct an arbitrary Chern vector that allows the emergence of surface-state torus knots or links on the surface of a single crystal. These results provide a complete picture of bulk-boundary correspondence for Chern vectors, and may find use in novel applications in topological acoustics

Effect of transanal drainage tube on prevention of anastomotic leakage after anterior rectal cancer surgery taking indwelling time into consideration: a systematic review and meta-analysis

BackgroundPlacement of an indwelling transanal drainage tube (TDT) to prevent anastomotic leakage (AL) after anterior rectal cancer surgery has become a routine choice for surgeons in the recent years. However, the specific indwelling time of the TDT has not been explored. We performed this meta-analysis and considered the indwelling time a critical factor in re-analyzing the effectiveness of TDT placement in prevention of AL after anterior rectal cancer surgery.MethodsRandomized controlled trials (RCTs) and cohort studies which evaluated the effectiveness of TDT in prevention of AL after rectal cancer surgery and considered the indwelling time of TDT were identified using a predesigned search strategy in databases up to November 2022. This meta-analysis was performed to estimate the pooled AL rates (Overall and different AL grades) and reoperation rates at different TDT indwelling times and stoma statuses.ResultsThree RCTs and 15 cohort studies including 2381 cases with TDT and 2494 cases without TDT were considered eligible for inclusion. Our meta-analysis showed that the indwelling time of TDT for ≥5-days was associated with a significant reduction (TDT vs. Non-TDT) in overall AL (OR=0.46,95% CI 0.34-0.60, p&lt;0.01), grade A+B AL (OR=0.64, 95% CI 0.42-0.97, p=0.03), grade C AL (OR=0.35, 95% CI 0.24-0.53, p&lt;0.01), overall reoperation rate (OR=0.36, 95%CI 0.24-0.53, p&lt;0.01) and that in patients without a prophylactic diverting stoma (DS) (OR=0.24, 95%CI 0.14-0.41, p&lt;0.01). There were no statistically significant differences in any of the abovementioned indicators (p&gt;0.05) when the indwelling time of TDT was less than 5 days.ConclusionExtending the postoperative indwelling time of TDT to 5 days may reduce the overall AL and the need for reoperation in patients without a prophylactic DS.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023407451, identifier CRD42023407451

Clinical characteristics and prognosis of 196 Chinese patients with colon cancer

AimsTo analyze the clinical characteristics and prognostic factors of Chinese patients with colon cancer.MethodsA retrospective analysis of the records of patients with colon cancer underwent surgery between 2014 and 2017 was performed. Univariate analysis in combination with Cox proportional hazard regression model was used to analyze the survival data, so as to reveal the prognostic factors of colon cancer. Data record was based on a standard data form. SPSS version 26.0 was used for data analysis (SPSS, Chicago, IL, United States).ResultsThe 3-year survival rate and the 5-year survival rate was 79.3% and 68.2%, respectively. Univariate analysis showed that radical surgery, laparoscopic surgery, ascites, swollen lymph nodes at the root of the mesentery, liver metastases, nerve invasion, vascular invasion, tumor node metastasis (TNM) staging, positive level of carbohydrate antigen (CA) 19-9, CA125, CA72-4 and combined detection were positive factors in the prognosis of colon cancer (P &lt; 0.05). Multivariate analysis showed that radical surgery and TNM staging were independent factors affecting the prognosis of patients with colon cancer (P &lt; 0.05).ConclusionRadical surgery and TNM staging have a significant impact on the prognosis of patients with colon cancer

An exploration of the correlations between seven psychiatric disorders and the risks of breast cancer, breast benign tumors and breast inflammatory diseases: Mendelian randomization analyses

BackgroundPrevious observational studies have showed that certain psychiatric disorders may be linked to breast cancer risk, there is, however, little understanding of relationships between mental disorders and a variety of breast diseases. This study aims to investigate if mental disorders influence the risks of overall breast cancer, the two subtypes of breast cancer (ER+ and ER-), breast benign tumors and breast inflammatory diseases.MethodsDuring our research, genome-wide association study (GWAS) data for seven psychiatric disorders (schizophrenia, major depressive disorder, bipolar disorder, post-traumatic stress disorder, panic disorder, obsessive-compulsive disorder and anorexia nervosa) from the Psychiatric Genomics Consortium (PGC) and the UK Biobank were selected, and single-nucleotide polymorphisms (SNPs) significantly linked to these mental disorders were identified as instrumental variables. GWAS data for breast diseases came from the Breast Cancer Association Consortium (BCAC) as well as the FinnGen consortium. We performed two-sample Mendelian randomization (MR) analyses and multivariable MR analyses to assess these SNPs’ effects on various breast diseases. Both heterogeneity and pleiotropy were evaluated by sensitivity analyses.ResultsWhen the GWAS data of psychiatric disorders were derived from the PGC, our research found that schizophrenia significantly increased the risks of overall breast cancer (two-sample MR: OR 1.05, 95%CI [1.03-1.07], p = 3.84 × 10−6; multivariable MR: OR 1.06, 95%CI [1.04-1.09], p = 2.34 × 10−6), ER+ (OR 1.05, 95%CI [1.02-1.07], p = 5.94 × 10−5) and ER- (two-sample MR: OR 1.04, 95%CI [1.01-1.07], p = 0.006; multivariable MR: OR 1.06, 95%CI [1.02-1.10], p = 0.001) breast cancer. Nevertheless, major depressive disorder only showed significant positive association with overall breast cancer (OR 1.12, 95%CI [1.04-1.20], p = 0.003) according to the two-sample MR analysis, but not in the multivariable MR analysis. In regards to the remainder of the mental illnesses and breast diseases, there were no significant correlations. While as for the data from the UK Biobank, schizophrenia did not significantly increase the risk of breast cancer.ConclusionsThe correlation between schizophrenia and breast cancer found in this study may be false positive results caused by underlying horizontal pleiotropy, rather than a true cause-and-effect relationship. More prospective studies are still needed to be carried out to determine the definitive links between mental illnesses and breast diseases

Synthesis and Biological Evaluation of Novel Allobetulon/Allobetulin–Nucleoside Conjugates as AntitumorAgents

Allobetulin is structurally similar tobetulinic acid, inducing the apoptosis of cancer cells with low toxicity. However, both of them exhibited weak antiproliferation against several tumor cell lines. Therefore, the new series of allobetulon/allobetulin–nucleoside conjugates 9a–10i were designed and synthesized for potency improvement. Compounds 9b, 9e, 10a, and 10d showed promising antiproliferative activity toward six tested cell lines, compared to zidovudine, cisplatin, and oxaliplatin based on their antitumor activity results. Among them, compound 10d exhibited much more potent antiproliferative activity against SMMC-7721, HepG2, MNK-45, SW620, and A549 human cancer cell lines than cisplatin and oxaliplatin. In the preliminary study for the mechanism of action, compound 10d induced cell apoptosis and autophagy in SMMC cells, resulting in antiproliferation and G0/G1 cell cycle arrest by regulating protein expression levels of Bax, Bcl-2, and LC3. Consequently, the nucleoside-conjugated allobetulin (10d) evidenced that nucleoside substitution was a viable strategy to improve allobetulin/allobetulon’s antitumor activity based on our present study

Towards interpreting recurrent neural networks through probabilistic abstraction

National Research Foundation (NRF) Singapore under its AI Singapore Programm