Escherichia coli O157:H7 senses microbiota-produced riboflavin to increase its virulence in the gut.

Riboflavin is produced by most commensal bacteria in the human colon, where enterohemorrhagic Escherichia coli (EHEC) colonizes and causes diseases. Sensing environmental signals to site-specifically express the type-III secretion system (T3SS), which injects effectors into host cells leading to intestinal colonization and disease, is key to the pathogenesis of EHEC. Here, we reveal that EHEC O157:H7, a dominant EHEC serotype frequently associated with severe diseases, acquired a previously uncharacterized two-component regulatory system rbfSR, which senses microbiota-produced riboflavin to directly activate the expression of LEE genes encoding the T3SS in the colon. rbfSR is present in O157:H7 and O145:H28 but absent from other EHEC serotypes. The binding site of RbfR through which it regulates LEE gene expression was identified and is conserved in all EHEC serotypes and Citrobacter rodentium, a surrogate for EHEC in mice. Introducing rbfSR into C. rodentium enabled bacteria to sense microbiota-produced riboflavin in the mouse colon to increase the expression of LEE genes, causing increased disease severity in mice. Phylogenic analysis showed that the O55:H7 ancestor of O157:H7 obtained rbfSR which has been kept in O157:H7 since then. Thus, acquiring rbfSR represents an essential step in the evolution of the highly pathogenic O157:H7. The expression of LEE genes and cell attachment ability of other EHEC serotypes in the presence of riboflavin significantly increased when rbfSR was introduced into them, indicating that those serotypes are ready to use RbfSR to increase their pathogenicity. This may present a potential public health issue as horizontal gene transfer is frequent in enteric bacteria.

Prevalence and risk factors of colorectal neoplasia in individuals aged 40-49 years: Findings from screening program in China.

BACKGROUND AND AIM: The incidence of colorectal cancer (CRC) in individuals under 50 is increasing worldwide. We conducted an analysis of colonoscopy findings in high-risk individuals under 50 in the CRC screening program in Tianjin, China, to determine the detection rate and risk factors of advanced adenomas (AA), advanced colorectal neoplasia (ACN), colorectal neoplasia (CN). METHODS: Our study investigated individuals aged 40-49 who underwent CRC screening and completed colonoscopy, 2012-2020, while the 50-54 age group served as a control. We compared the detection rates of AA, ACN, and CN among three age groups using univariate and multivariable logistic regression analyses, and investigated the risk factors associated with AA, ACN, and CN among individuals aged 40-49. RESULTS: We found a gradual increase in the detection rate of AA, ACN, and CN among individuals aged 40-54. The detection rates for AA (OR 0.58; 95% CI 0.41-0.81), ACN (OR 0.58; 95% CI 0.43-0.77), and CN (OR 0.64; 95% CI 0.56-0.74) were lower in individuals aged 40-44 compared to 45-49. The detection rates of AA (OR 1.08; 95% CI 0.87-1.34) and ACN (OR 1.12; 95% CI 0.93-1.35) in individuals aged 45-49 were comparable with 50-54. Besides, lifestyle factors, BMI, and FIT are not associated with the detection rates of AA, ACN, and CN among individuals aged 40-49. CONCLUSIONS: Our study reveals screening data in individuals under 50, indicating comparable detection rates of AA and ACN in individuals aged 45-49 and 50-54. These findings provide valuable data support for optimizing the optimal age to initiate screening.

The Long-Term Outcome of Laparoscopic Resection for Perihilar Cholangiocarcinoma Compared with the Open Approach: A Real-World Multicentric Analysis.

OBJECTIVE: The aim of this study was to compare the short- and long-term outcomes of laparoscopic surgery (LS) and open surgery (OP) for perihilar cholangiocarcinoma (PHC) using a large real-world dataset in China. METHODS: Data of patients with PHC who underwent LS and OP from January 2013 to October 2018, across 10 centers in China, were extracted from medical records. A comparative analysis was performed before and after propensity score matching (PSM) in the LS and OP groups and within the study subgroups. The Cox proportional hazards mixed-effects model was applied to estimate the risk factors for mortality, with center and year of operation as random effects. RESULTS: A total of 467 patients with PHC were included, of whom 161 underwent LS and 306 underwent OP. Postoperative morbidity, such as hemorrhage, biliary fistula, abdominal abscess, and hepatic insufficiency, was similar between the LS and OP groups. The median overall survival (OS) was longer in the LS group than in the OP group (NA vs. 22 months; hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.02-1.39, p = 0.024). Among the matched datasets, OS was comparable between the LS and OP groups (NA vs. 35 months; HR 0.99, 95% CI 0.77-1.26, p = 0.915). The mixed-effect model identified that the surgical method was not associated with long-term outcomes and that LS and OP provided similar oncological outcomes. CONCLUSIONS: Considering the comparable long-term prognosis and short-term outcomes of LS and OP, LS could be a technically feasible surgical method for PHC patients with all Bismuth-Corlett types of PHC.

Laparoscopic versus open surgery for perihilar cholangiocarcinoma: a multicenter propensity score analysis of short- term outcomes.

BACKGROUND: Laparoscopic surgery (LS) has been increasingly applied in perihilar cholangiocarcinoma (pCCA). In this study, we intend to compare the short-term outcomes of LS versus open operation (OP) for pCCA in a multicentric practice in China. METHODS: This real-world analysis included 645 pCCA patients receiving LS and OP at 11 participating centers in China between January 2013 and January 2019. A comparative analysis was performed before and after propensity score matching (PSM) in LS and OP groups, and within Bismuth subgroups. Univariate and multivariate models were performed to identify significant prognostic factors of adverse surgical outcomes and postoperative length of stay (LOS). RESULTS: Among 645 pCCAs, 256 received LS and 389 received OP. Reduced hepaticojejunostomy (30.89% vs 51.40%, P = 0.006), biliary plasty requirement (19.51% vs 40.16%, P = 0.001), shorter LOS (mean 14.32 vs 17.95 d, P < 0.001), and lower severe complication (CD ≥ III) (12.11% vs. 22.88%, P = 0.006) were observed in the LS group compared with the OP group. Major postoperative complications such as hemorrhage, biliary fistula, abdominal abscess, and hepatic insufficiency were similar between LS and OP (P > 0.05 for all). After PSM, the short-term outcomes of two surgical methods were similar, except for shorter LOS in LS compared with OP (mean 15.19 vs 18.48 d, P = 0.0007). A series subgroup analysis demonstrated that LS was safe and had advantages in shorting LOS. CONCLUSION: Although the complex surgical procedures, LS generally seems to be safe and feasible for experienced surgeons. TRIAL REGISTRATION: NCT05402618 (date of first registration: 02/06/2022).

Resveratrol attenuates radiation enteritis through the SIRT1/FOXO3a and PI3K/AKT signaling pathways.

Radiation enteritis (RE) is the most common radiotherapy complication, and effective RE treatments are lacking. Resveratrol exerts beneficial effects on radiation injury. However, the effect of resveratrol in radiation-induced intestinal injury and the underlying mechanism remain unclear. Here, a C57BL/6 mouse model of RE was established and an intestinal epithelial cell line was used to evaluate the protective effects of resveratrol against radiation-induced intestinal injury and the underlying mechanisms. Resveratrol improved radiation-induced oxidative stress and cell apoptosis via upregulating antioxidant enzymes and downregulating p53 acetylation. In vivo, resveratrol-treated mice exhibited longer survival; longer villi; more intestinal crypt cells; upregulated expression of Ki67, catalase, and superoxide dismutase 2; and fewer inflammatory proteins and apoptotic cells. These protective effects were suppressed by inhibition of SIRT1. These results demonstrate that resveratrol can reduce radiation-induced intestinal injury by inhibiting oxidative stress and apoptosis via the SIRT1/FOXO3a and PI3K/AKT pathways.

Habitually skipping breakfast is associated with chronic inflammation: a cross-sectional study.

OBJECTIVE: We examined whether breakfast frequency was associated with chronic inflammatory, as assessed by high-sensitivity C-reactive protein (CRP) concentration. DESIGN: Cross-sectional study. SETTING: Kailuan community, China. PARTICIPANTS: Included were 70 092 Chinese adults without CVD and cancer in 2014 with CRP concentrations <10 mg/l, when breakfast frequency was assessed via a questionnaire, and plasma CRP concentration was measured. RESULTS: Breakfast frequency was associated with CRP concentration (P-trend < 0·001). The adjusted mean CRP was 1·33 mg/l (95 % CI 1·23, 1·44) for the 'no breakfast' group and 1·07 mg/l (95 % CI 1·0, 1·14) for the 'breakfast everyday' group (P-difference < 0·001), adjusting for age, sex, diet quality, total energy, obesity, education, occupation, marital status, smoking, alcohol consumption, blood pressure, sleep parameters, fasting blood glucose and lipid profiles. Consistently, the adjusted OR for CRP ≥ 1·0 mg/l and CRP ≥ 3·0 mg/l were 1·86 (95 % CI 1·73, 2·00) and 1·27 (95 % CI 1·15, 1·40), respectively, when comparing these two breakfast consumption groups (P-trend < 0·001 for both). The associations were more pronounced among older adults, relative to those who were younger (P-interaction < 0·001). Significant association between breakfast skipping and elevated CRP concentration was observed in those with poor diet quality, but not those with good diet quality. CONCLUSIONS: Habitually skipping breakfast is associated with elevated concentrations of CRP. Future prospective studies including repeated assessment of inflammatory biomarkers and a collection of detailed information on type and amount of breakfast foods are warranted.

Study on anti-scaling of landfill leachate treated by evaporation method.

In the mechanical vapor recompression (MVR) treatment of landfill leachate, scaling in the evaporator and heat exchanger poses a serious problem. This study explored the reasons for such scaling and proposed acid or ion-exchange pre-treatments to reduce the alkalinity of the landfill leachate nanofiltration concentrate (LLNC) to prevent scaling. The feasibility of these two methods was evaluated and the technical and economic parameters for application were obtained via experiments. A large amount of HCO3- in the LLNC was the main cause of scaling. The acid addition experiment and field application demonstrated that this method could prevent fouling problems. The cost of acid addition was USD 0.18/t. LLNC pre-treatment by ion-exchange showed that a weakly acidic cation-exchange resin performed better than a strongly acidic cation-exchange resin did. The amount of solid residue under an alkalinity of 0 mg/L could be decreased by 92.9% compared with that of raw LLNC during evaporation. Both methods could alleviate scaling and enable the wide application of the MVR evaporation process in landfill leachate treatment.

microRNA-329 suppresses epithelial-to-mesenchymal transition and lymph node metastasis in bile duct cancer by inhibiting laminin subunit beta 3.

Bile duct cancer (BDC), also known as cholangiocarcinoma, is a highly desmoplastic cancer with a growth pattern characterized by periductal extension and infiltration. Studies have suggested that microRNAs (miRNAs) play an important role in BDC progression. Here we aim at investigating the effects of miR-329 on BDC development, focusing especially on epithelial-to-mesenchymal transition (EMT) in vitro and lymph node metastasis in vivo. Expression microarrays associated with BDC tissues were collected and differentially expressed genes were analyzed, followed by miRNA target prediction and verification. The role miR-329 played in BDC was examined using gain-of-function and loss-of-function methods. The expressions of miR-329, laminin subunit beta 3 (LAMB3), and EMT markers, in addition to cell proliferation, migration, and invasion were evaluated. Furthermore, nude mice models of BDC were established to observe tumor growth and metastatic lymph nodes. The LAMB3 was identified as an upregulated gene based on the GSE77984 and GSE45001 microarray analysis. LAMB3 was also predicted and confirmed to be a target gene of miR-329 by dual-luciferase reporter assay. Through further cell experiments, the EMT process was reversed, cell proliferation, invasion, and migration were suppressed, when miR-329 was upregulated. Furthermore, in vivo experiments exhibited that the overexpression of miR-329 inhibited tumor growth and the number of metastatic lymph nodes. This study provides in vivo and in vitro evidence that miR-329 inhibits BDC progression through translational repression of LAMB3. Therefore, the obtained results may aid as an experimental basis for improving prognosis of BDC.

Refractive index sensing and imaging based on polarization-sensitive graphene.

Graphene exhibits extraordinary opto-electronic properties due to its unique dynamic conductivity, bringing great value in optical sensing, surface plasmon modulation and photonic devices. Based on the polarization-sensitive absorption of graphene working at near infrared to ultraviolet wavelengths, we theoretically investigate the refractive index sensing and imaging mechanism under oblique and tight focusing incidences of light respectively. We demonstrate that such graphene-based methods can provide ultrahigh refractive index resolution (∼2.09×10-8 RIU) for label-free sensing, and high transverse spatial resolution (∼200 nm) and large longitudinal detecting length (∼750 nm) for imaging under 532 nm incident wavelength. The proposed methods could potentially guide future researches in graphene optical detection, non-invasive biological sensing and imaging, and other applications.

The role of mSEPT9 in screening, diagnosis, and recurrence monitoring of colorectal cancer.

BACKGROUND: The application of circulating, cell-free, methylated Septin9 (mSEPT9) DNA in screening and recurrence monitoring is highly promising. CpG island methylator phenotype (CIMP) is associated with microsatellite instability (MSI). The present study was performed to determine the diagnostic accuracy of mSEPT9 for colorectal cancer (CRC) and to evaluate its utility in CRC screening and recurrence monitoring. METHODS: For screening and diagnosis of CRC, peripheral mSEPT9 detection and fecal occult blood test (FOBT) were performed in 650 subjects, then the level of CEA, CA19-9 and CA724 was quantified in 173 subjects. Clinicopathological parameters and mismatch repair protein were detected among subjects with CRC. For recurrence monitoring of CRC, the sensitivity of mSEPT9 of 70 subjects was compared with tumor markers and contrast enhanced computed tomography (CECT). RESULTS: Seventy-three percent of CRC patients were mSEPT9-positive at 94.5% specificity, and 17.1% of patients with intestinal polyps and adenoma were mSEPT9-positive at 94.5% specificity, which were higher than FOBT for the screening of CRC. The sensitivity and specificity of mSEPT9 for diagnosis and recurrence monitoring were higher than that of CEA, CA19-9 and CA724. The combined detection of mSEPT9 and CECT enhanced the sensitivity for recurrence monitoring. Pre-therapeutic levels of mSEPT9 were strongly associated with TNM stage, Dukes stages and mismatch repair deficiency (dMMR). CONCLUSIONS: mSEPT9 analysis might be popularized as a routine biomarker for CRC screening. The combined detection of mSEPT9 and CECT can play an important role for recurrence monitoring. CIMP was highly associated with the pathological stage of CRC and dMMR.

Nonlinearity-Induced Multiplexed Optical Trapping and Manipulation with Femtosecond Vector Beams.

Optical trapping and manipulation of atoms, nanoparticles, and biological entities are widely employed in quantum technology, biophysics, and sensing. Single traps are typically achieved with linearly polarized light, while vortex beams form rotationally unstable symmetric traps. Here we demonstrate multiplexed optical traps reconfigurable with intensity and polarization of the trapping beam using intensity-dependent polarizability of nanoparticles. Nonlinearity combined with a longitudinal field of focused femtosecond vortex beams results in a stable optical force potential with multiple traps, in striking contrast to a linear trapping regime. The number of traps and their orientation can be controlled by the cylindrical vector beam order, polarization, and intensity. The nonlinear trapping demonstrated here on the example of plasmonic nanoparticles opens up opportunities for deterministic trapping and polarization-controlled manipulation of multiple dielectric and semiconductor particles, atoms, and biological objects since most of them exhibit a required intensity-dependent refractive index.

Application of multiplex immunoassay technology to investigations of ocular disease.

Eye-derived fluids, including tears, aqueous humour and vitreous humour often contain molecular signatures of ocular disease states. These signatures can be composed of cytokines, chemokines, growth factors, proteases and soluble receptors. However, the small quantities (<10 µl) of these fluids severely limit the detection of these proteins by traditional enzyme-linked immunosorbent assay or Western blot. To maximise the amount of information generated from the analysis of these specimens, many researchers have employed multiplex immunoassay technologies for profiling the expression or modification of multiple proteins from minute sample volumes.

Sub-wavelength sized transversely polarized optical needle with exceptionally suppressed side-lobes.

It is well known that radially polarized beam could produce an ultra-long longitudinally polarized focus, referred to as "optical needle". In this work, we reveal that the counterpart transversely polarized optical needle (~5.83λ) with exceptionally suppressed sidelobes (9.9% of the maximum of the principal lobe) can be generated by tightly focusing a hybridly polarized beam through a multibelt binary phase filter. A universal analytical model is built up for investigating the depth, uniformity and polarization properties of the needle. We find that there is a trade-off between needle length and intensity uniformity, and the main lobe keeps almost transverse polarization at each observation plane. Such a nondiffraction transversely polarized optical needle has potential applications in ultrahigh density magnetic storage as well as atomic trap and switches.

Chemically modified graphene films for high-performance optical NO2 sensors.

Various graphene-based gas sensors that operate based on the electrical properties of graphene have been developed for accurate detection of gas components. However, electronic graphene-based gas sensors are unsafe under explosive atmospheres and sensitive to electromagnetic interference. Here, a novel optical graphene-based gas sensor for NO2 detection is established based on surface chemical modification of high-temperature-reduced graphene oxide (h-rGO) films with sulfo groups. Sulfo group-modified h-rGO (S-h-rGO) films with a thickness of several nanometers exhibit excellent performance in NO2 detection at room temperature and atmospheric pressure based on the polarization absorption effect of graphene. Initial slope analysis of the S-h-rGO sensor indicates that it has a limit of detection of 0.28 ppm and a response time of 300 s for NO2 gas sensing. Furthermore, the S-h-rGO sensor also possesses the advantages of good linearity, reversibility, selectivity, non-contact operation, low cost and safety. This novel optical gas sensor has the potential to serve as a general platform for the selective detection of a variety of gases with high performance.

Plasmonic hybridization induced trapping and manipulation of a single Au nanowire on a metallic surface.

Hybridization in the narrow gaps between the surface plasmon polaritons (SPPs) along a metal surface and the localized surface plasmons on metallic nano-objects strongly enhance the electromagnetic field. Here, we employ plasmonic hybridization to achieve dynamic trapping and manipulation of a single metallic nanowire on a flat metal surface. We reveal that the plasmonic hybridization achieved by exciting plasmonic tweezers with a linearly polarized laser beam could induce strong trapping forces and large rotational torques on a single metallic nanowire. The position and orientation of the nanowire could dynamically be controlled by the hybridization-enhanced nonisotropic electric field in the gap. Experimental results further verify that a single Au nanowire could robustly be trapped at the center of an excited SPP field by the induced forces and then rotated by the torques. Finally, a plasmonic swallow tail structure is built to demonstrate its potential in the fabrication of lab-on-a-chip plasmonic devices.

Tight focusing of quasi-cylindrically polarized beams.

Based on vectorial diffraction theory, tight focusing properties of quasi-cylindrical polarized beams (QCPBs) composed of equal fan-shaped sectors with linear polarization are investigated. We find that, for quasi-radially polarized illumination, a weak azimuthal component emerges and the circular symmetry of focus is traded in when the total number of sector N is small, but when N≥8 it is approaching that of a perfect radially polarized beam with a deviation smaller than 5.3% and a ratio of maximum total intensity larger than 95.5%. Meanwhile, for quasi-azimuthal polarized illumination, although weak radial and longitudinal components emerge, it is also close to that of the perfect azimuthally polarized beam when N≥8 with deviation smaller than 5.3% and a ratio larger than 95.0%. These results not only reveal a deep understanding of the focusing properties of QCPBs, but also provide an important contribution toward optimization of the monolithic methods for generating vector beams.

Phase-stepping technique for highly sensitive microscopic surface plasmon resonance biosensor.

In this paper, the phase-stepping technique is applied to improve a phase-sensitive surface plasmon resonance biosensor based on differential interferometry between focused radially polarized and azimuthally polarized cylindrical vector beams. Detailed analysis is presented for the phase-stepping method, and the least squares unwrapping algorithm is employed to detect the phase distribution in correspondence to the refractive index of sample. Benefiting from the phase-stepping technique, both the measurement speed and sensitivity are improved significantly. The proposed sensor maintains high sensitivity of 9.4×10-7 RIU/1° and a wide dynamic range of 0.35 RIU simultaneously. Furthermore, the real-time binding reaction process of bovine serum albumin with antibody is monitored to verify the system for potential biological applications.

Measurement of the microscopic viscosities of microfluids with a dynamic optical tweezers system.

Viscosity coefficients of microfluids-Newtonian and non-Newtonian-were explored through the rotational motion of a particle trapped by optical tweezers in a microflute. Unlike conventional methods based on viscometers, our microfluidic system employs samples of less than 30 µl to complete a measurement. Viscosity coefficients of ethanol and fetal bovine serum, as typical examples of Newtonian and non-Newtonian fluids, were obtained experimentally, and found to be in excellent agreement with theoretical predictions. Additionally, a practical application to a DNA solution with incremental ethidium bromide content was employed and the results are consistent with clinical data, indicating that our system provides a potentially important complementary tool for use in such biological and medical applications.

Tumor-draining lymph nodes: opportunities, challenges, and future directions in colorectal cancer immunotherapy.

Tumor-draining lymph nodes (TDLNs) are potential immunotherapy targets that could expand the population of patients with colorectal cancer (CRC) who may benefit from immunotherapy. Currently, pathological detection of tumor cell infiltration limits the acquisition of immune information related to the resected lymph nodes. Understanding the immune function and metastatic risk of specific stages of lymph nodes can facilitate better discussions on the removal or preservation of lymph nodes, as well as the timing of immunotherapy. This review summarized the contribution of TDLNs to CRC responses to immune checkpoint blockade therapy, local immunotherapy, adoptive cell therapy, and cancer vaccines, and discussed the significance of these findings for the development of diagnostics based on TDLNs and the potential implications for guiding immunotherapy after a definitive diagnosis. Molecular pathology and immune spectrum diagnosis of TDLNs will promote significant advances in the selection of immunotherapy options and predicting treatment efficacy.