Engineered Bacteria for Visualization and Localization of Gastrointestinal Bleeding: A Promising Application.

Gastrointestinal bleeding, especially obscure gastrointestinal bleeding (OGIB), is a common and serious clinical emergency with a notable incidence rate. However, the current diagnostic method, gastroscopy, is invasive and often struggles to efficiently detect microhemorrhagic lesions, leading to diagnostic challenges and potential misdiagnoses. Here, we developed an intelligently engineered bacterium utilizing synthetic biology techniques for in vivo localization detection of gastrointestinal bleeding. By constructing three gene circuit modules within E. coli Nissle 1917 for heme recognition, response, and output generation, we have successfully enabled specific heme sensing and real-time optical signal production in vivo. This innovative strategy overcomes the limitations of the existing diagnostic methods, offering a noninvasive and precise means of detecting gastrointestinal bleeding. These advancements hold promise for enhancing diagnostic accuracy and treatment efficacy in future clinical settings within the realm of gastroenterology.

Quantifying carboxymethyl lysine and carboxyethyl lysine in human plasma: clinical insights into aging research using liquid chromatography-tandem mass spectrometry.

OBJECTIVE: The objective of this study was to establish a methodology for determining carboxymethyl lysine (CML) and carboxyethyl lysine (CEL) concentrations in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The test results were also used for clinical aging research. METHODS: Human plasma samples were incubated with aqueous perfluorovaleric acid (NFPA), succeeded by precipitation utilizing trichloroacetic acid, hydrolysis facilitated by hydrochloric acid, nitrogen drying, and ultimate re-dissolution utilizing NFPA, followed by filtration. Cotinine-D3 was added as an internal standard. The separation was performed on an Agela Venusil ASB C18 column (50 mm × 4.6 mm, 5 µm) with a 5 mmol/L NFPA and acetonitrile/water of 60:40 (v/v) containing 0.15% formic acid. The multiple reaction monitoring mode was used for detecting CML, CEL, and cotinine-D3, with ion pairs m/z 205.2 > 84.1 (for quantitative) and m/z 205.2 > m/z 130.0 for CML, m/z 219.1 > 84.1 (for quantitative) and m/z 219.1 > m/z 130.1 for CEL, and m/z 180.1 > 80.1 for cotinine-D3, respectively. RESULTS: The separation of CML and CEL was accomplished within a total analysis time of 6 minutes. The retention times of CML, CEL, and cotinine-D3 were 3.43 minutes, 3.46 minutes, and 4.50 minutes, respectively. The assay exhibited linearity in the concentration range of 0.025-1.500 µmol/L, with a lower limit of quantification of 0.025 µmol/L for both compounds. The relative standard deviations of intra-day and inter-day were both below 9%, and the relative errors were both within the range of ±4%. The average recoveries were 94.24% for CML and 97.89% for CEL. CONCLUSION: The results indicate that the developed methodology is fast, highly sensitive, highly specific, reproducible, and suitable for the rapid detection of CML and CEL in clinical human plasma samples. The outcomes of the clinical research project on aging underscored the important indicative significance of these two indicators for research on human aging.

The value of the wireless stethoscope in patients with COVID-19 infection in a makeshift hospital.

OBJECTIVE: When COVID-19 sweeps the world, traditional stethoscopes are seen as infectious agents and then the use of stethoscopes is limited especially when health providers were in their personal protective equipment. These reasons led to the ignoring of the values of stethoscopes during pandemics. This study aims to explore the value of wireless stethoscopes in patients of a makeshift hospital. MATERIAL AND METHODS: 200 consecutive hospitalized patients with confirmed SARS-CoV-2 at Lingang Makeshift Hospital in Shanghai, China, were enrolled from April 10 to May 10, 2022 (Trial Registration Number: ChiCTR2000038272,2020/9/15). They were randomly divided into two groups. In group A (n = 100), patients were examined without a stethoscope. In group B (n = 100), lung breath sounds and heart sounds were examined with a wireless stethoscope, and positive signs were recorded. The duration of cough and tachycardia symptoms, as well as emergency cases, were compared between the two groups. In addition, the pressure, anxiety, and depression of patients in the two groups were investigated using the DAS-21 questionnaire scale, to observe the psychological impact of the stethoscope-based doctor-patient communication on patients in the makeshift hospital. RESULTS: There was no significant difference in baseline characteristics between the two groups. In group B, some significant positive signs were detected by wireless stethoscopes, including pulmonary rales and tachycardia, etc. Moreover, the therapeutic measures based on these positive signs effectively alleviated the symptoms of cough and tachycardia, which showed that the duration of symptoms was significantly shorter than that of group A (cough: 2.8 ± 0.9 vs. 3.6 ± 0.9; palpitation: 1.4 ± 0.7 vs. 2.6 ± 0.7). In particular, the number of emergency cases in group B is less than that in group A (1% vs. 3%), and the severity is lower. Notably, stethoscope-based doctor-patient communication was found to be effective in alleviating psychological measures of group B patients. CONCLUSION: Wireless stethoscopes in makeshift hospitals can avoid cross-infections and detect more valuable positive signs, which can help health providers make accurate decisions and relieve patients' symptoms more quickly. Moreover, stethoscope-based doctor-patient communication can diminish the psychological impacts of the epidemic on isolated patients in makeshift hospitals. Trial registration This study was registered in the Chinese Clinical Trial (ChiCTR2000038272) at http://www.chictr.org.cn . http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml .

Identification of regionalmarkers based on the flavor molecular matrix analysis of sauce-aroma style baijiu.

BACKGROUND: Baijiu is a very complex system and its flavor substances are endogenous, influenced by raw materials, starter, production process, production region and other factors. The production region directly affects the composition of flavor substances and quality of baijiu. However, identification of baijiu region is challenging because the corresponding relationship between the production region and baijiu quality is not clear, and the identification of regionalmarkers is indeterminate. In this study, the differences in volatile components of sauce-aroma style baijiu from four representative regions were investigated. RESULTS: A total of 94 volatile compounds were identified in samples tested. Additionally, it was verified that 35 potential flavor substances had important contributions to the aroma of sauce-aroma style baijiu. Meanwhile, nine potential regionalmarkers were screened through multivariate analysis. Further, based on distribution of volatile compounds and the results of sensory evaluation combined with multivariate analysis, a molecular matrix and correlation network were established according to the results of addition experiments, which showed that six substances had a significant impact on the flavor of the tested samples. CONCLUSION: Six key flavor substances (ethyl octanoate, ethyl 2-methylpropanoate, propyl acetate, ethyl heptanoate, 2-nonanone and butyl hexanoate) were considered as important regionalmarkers to effectively identify the production region of sauce-aroma style baijiu. © 2023 Society of Chemical Industry.

Combination therapy of bezafibrate and ursodeoxycholic acid for primary biliary cirrhosis: A meta-analysis.

The aim of this study was to assess the efficiency and safety of combination therapy of ursodeoxycholic acid (UDCA) and bezafibrate for primary biliary cirrhosis. A meta-analysis of all long-term randomized controlled trials comparing the combination of UDCA and bezafibrate with UDCA monotherapy was performed via electronic searches. Seven trials, which included 177 patients, were assessed. Combination therapy with UDCA and bezafibrate was more effective than UDCA monotherapy in improving liver biochemistry, alkaline phosphatase (mean difference [MD], -146.15 IU/L; 95% confidence interval [CI], -193.58 to -98.72; P < 0.00001), γ-glutamyltransferase (MD, -20.64 IU/L; 95% CI, -30.86 to -10.43; P < 0.0001), immunoglobulin M (MD, -90.96 mg/dL; 95% CI, -137.36 to -44.56; P = 0.0001) and triglycerides (MD, -15.49 mg/dL; 95% CI, -30.25 to -0.74; P = 0.04). However, their effects on pruritus (odds ratio [OR], 0.82; 95% CI, 0.30-2.24; P = 0.70) and alanine aminotransferase (MD, -8.41 IU/L; 95% CI, -22.57 to 5.75; P = 0.24) did not differ significantly. This meta-analysis revealed no significant differences in the incidence of all-cause mortality (OR, 0.72; 95% CI, 0.10-5.49; P = 0.75) and adverse events (OR, 0.35; 95% CI, 0.07-1.84; P = 0.22) between patients treated with combination therapy and those treated with monotherapy. In this meta-analysis, combination therapy with UDCA and bezafibrate was more effective than UDCA monotherapy. Combination therapy improved liver biochemistry, but did not improve clinical symptoms, incidence of death or adverse events more effectively than monotherapy.

Protective effects of N-acetylcysteine in concanavalin A-induced hepatitis in mice.

This study was designed to study the protective effects and mechanisms of N-acetylcysteine (NAC) in concanavalin A-induced hepatitis in mice. In this study, pretreatment with NAC ameliorated the histopathological changes and suppressed inflammatory cytokines in ConA-induced hepatitis. The expression of IL-2, IL-6, TNF-α, and IFN-γ was significantly reduced in the NAC-treated groups. NAC activated PI3K/Akt pathway and inhibited the activation of NF-κB. Additionally, NAC reduced autophagosome formation, as assessed by detecting the expression of LC3 and Beclin 1. Our results demonstrate that NAC can alleviate ConA-induced hepatitis by regulating the PI3K/Akt pathway and reducing the late stages of autophagy. Our results described a new pharmaceutical to provide more effective therapies for immune hepatitis.

Identifying Mixed Dementia With Lewy Bodies and Alzheimer Disease Using Multitracer PET Imaging: A Case Study.

ABSTRACT: We reported imaging findings with complex signs that were corresponded with both dementia with Lewy bodies (DLB) and Alzheimer disease (AD) in the case of a 78-year-old woman. Initially suspected as DLB due to cognitive and movement issues, diagnostic support included the cingulate island sign on 18 F-FDG PET, positive 131 I-MIBG cardiac scintigraphy, and DAT PET. However, MRI indicated hippocampal atrophy, and 18 F-FDG PET showed hypometabolism in the medial temporal lobe, suggesting the possibility of concomitant AD. Subsequent detection of ß-amyloid pathology and tau accumulation in the brain further supported the concurrent presence of AD pathology.

The role of KNTC1 in the regulation of proliferation, migration and tumorigenesis in colorectal cancer.

BACKGROUND: Current findings have revealed that kinetochore-associated protein 1 (KNTC1) plays a pivotal role in the carcinogenesis of numerous types of cancer. This study was undertaken to inspect the role and probable underlying mechanisms of KNTC1 during the genesis and progression of colorectal cancer. METHODS: Immunohistochemistry was implemented to determine KNTC1 expression levels in colorectal cancer tissues and para-carcinoma tissues. The association between KNTC1 expression profiles and several clinicopathological traits of colorectal cancer cases was examined employing Mann-Whitney U, Spearman, and Kaplan-Meier analyses. To track the proliferation, apoptosis, cell cycle, migration and in vivo carcinogenesis of colorectal cancer cells, KNTC1 was knocked down in colorectal cell line via RNA interference. To investigate the potential mechanism, the expression profile alterations of associated proteins were detected using human apoptosis antibody arrays, and verified by Western blot analysis. RESULTS: In colorectal cancer tissues, KNTC1 was substantially expressed, and it was associated with the pathological grade as well as overall survival rate of the disease. The knockdown of KNTC1 was able to inhibit proliferation, cell cycle, migration and in vivo tumorigenesis of colorectal cancer cells, but promote apoptosis. CONCLUSIONS: KNTC1 is a key player in the emergence of colorectal cancer and may serve as an early diagnostic indicator of precancerous lesions.

Canine model of electrical conduction recurrence after radiofrequency catheter ablation constructed by CARTO3 and preliminary application evaluation of DOX-L.

BACKGROUND: Radiofrequency catheter ablation (RFCA) is widely used to treat arrhythmias. However, for atrial fibrillation, the recurrence rate after RFCA is still high. The development of an animal model that mimics the recurrence of electrical conduction after ablation is essential before we can explore the mechanisms involved or develop new therapeutic strategies. METHODS: Eighteen beagles aged 12 to 24 months were randomly assigned to this study. RFCA ablation of the right atrial free wall was performed. Then, electrical block and conduction recovery in the ablation area were evaluated using voltage mapping and pacing tests assisted by CARTO3 system. Finally, liposome doxorubicin (DOX-L) was intravenously injected after ablation to investigate the effect of DOX-L on this animal model. RESULTS: The conduction block (CB) rates at 5 min after ablation were 16.7%, 83.3%, and 100%, corresponding to 30w, 35w, and 40w power, respectively. However, after 20 min, the rate of CB was 0%, 33.3%, and 75%; thus, the combined success rate of CB and conduction recurrence was 16.7%, 50%, and 25%, respectively. The optimal ablation parameter is 35 W for 20 s, based on the CB rate, REC rate. After 10 days of ablation, the residual conduction recurrence rate was as high as 83.3% in the RFCA alone group, whereas there was no recurrence with RFCA combined with DOX-L treatment. CONCLUSIONS: The novel model accurately simulated the electrical conduction recurrence after cardiac radiofrequency ablation. RFCA combined with DOX-L treatment dramatically reduces the recurrence rate of electrical conduction after ablation.

pH-Sensitive Nanoparticles for Colonic Delivery Anti-miR-301a in Mouse Models of Inflammatory Bowel Diseases.

Though the anti-miR-301a (anti-miR) is a promising treatment strategy for inflammatory bowel disease (IBD), the degradability and the poor targeting of the intestine are a familiar issue. This study aimed to develop a multifunctional oral nanoparticle delivery system loaded with anti-miR for improving the targeting ability and the therapeutic efficacy. The HA-CS/ES100/PLGA nanoparticles (HCeP NPs) were prepared using poly (lactic-co-glycolic acid) copolymer (PLGA), enteric material Eudragit®S100 (ES100), chitosan (CS), and hyaluronic acid (HA). The toxicity of nanoparticles was investigated via the Cell Counting Kit-8, and the cellular uptake and inflammatory factors of nanoparticles were further studied. Moreover, we documented the colon targeting and pharmacodynamic properties of nanoparticles. The nanoparticles with uniform particle size exhibited pH-sensitive release, favorable gene protection, and storage stability. Cytology experiments showed that anti-miR@HCeP NPs improved the cellular uptake through HA and reduced pro-inflammatory factors. Administering anti-miR@HCeP NPs orally to IBD mice markedly reduced their pro-inflammatory factors levels and disease activity indices. We also confirmed that anti-miR@HCeP NPs mostly accumulated in the colon site, and effectively repaired the intestinal barrier, as well as relieved intestinal inflammation. The above nanoparticle is a candidate of the treatment for IBD due to its anti-inflammatory properties.

Coupling split-lux cassette with a toggle switch in bacteria for ultrasensitive blood markers detection in feces and urine.

Cell-based biosensors have powerful abilities to sense a variety of signal chemical molecules. However, compared with commercialized methods, whole-cell biosensors cannot meet the requirements for the lower sensitivity and faster response. Here, we reprogrammed a gene circuit by coupling split-lux cassette with a toggle switch for detecting heme ultra-sensitively. The resultant biosensor (named YES601) exhibited improved detection limit (0.12 ppm) and satisfied maximum induction ratio (more than 4000 folds) for lysed blood detection. Furthermore, we harnessed YES601 to detect the blood signal in the human urine and feces from the mice with DSS-induced colitis, and the results indicated that YES601 showed more satisfied sensitivity and maximum induction ratio compared with chemical method. This ultrasensitive blood biosensor will be applied to detect trace blood in vitro for early-stage diagnosis of serious diseases, and aiding the rapid development for application in diagnosis in vivo in the future.

"Key Factor" for Baijiu Quality: Research Progress on Acid Substances in Baijiu.

Baijiu is the national liquor of China, which has lasted in China for more than 2000 years. Abundant raw materials, multi-strain co-fermentation, and complex processes make the secrets of baijiu flavor and taste still not fully explored. Acid substances not only have a great influence on the flavor and taste of baijiu, but also have certain functions. Therefore, this paper provides a systematic review for the reported acid substances, especially for their contribution to the flavor and functional quality of baijiu. Based on previous studies, this paper puts forward a conjecture, a suggestion, and a point of view, namely: the conjecture of "whether acid substances can be used as 'key factor' for baijiu quality "; the suggestion of "the focus of research on acid substances in baijiu should be transferred to evaluating their contribution to the taste of baijiu"; and the view of "acid substances are 'regulators' in the fermentation process of baijiu". It is worth thinking about whether acid substances can be used as the key factors of baijiu to be studied and confirmed by practice in the future. It is hoped that the systematic review of acid substances in baijiu in this paper can contribute to further in-depth and systematic research on baijiu by researchers in the future.

Uncover the Flavor Code of Roasted Sesame for Sesame Flavor Baijiu: Advance on the Revelation of Aroma Compounds in Sesame Flavor Baijiu by Means of Modern Separation Technology and Molecular Sensory Evaluation.

Baijiu occupies an important position in the food industry of China and is deeply recognized as the national liquor of China. According to the flavor characteristics, Baijiu is artificially divided into 12 categories. The sesame flavor of Baijiu was accidentally discovered after the founding of the People's Republic of China. Sesame flavor Baijiu is known for its special aroma of roasted sesame, which attracts people's attention. Modern flavor extraction, separation technology, and flavor analysis technology, greatly promote the identification and evaluation of trace components and aroma compounds in Baijiu. Of note, it has successfully identified which aroma compounds are responsible for the special roasted sesame aroma in sesame flavor Baijiu. On this basis, this paper summarizes the extraction methods, detection techniques, analysis methods, aroma expression, and sensory evaluation methods that have been applied for the verification and evaluation of trace components and aroma compounds in Baijiu. More specifically, the research progress on the revelation of aroma compounds in sesame flavor Baijiu is systematically summarized. Next, people will focus on the changing mechanisms of aroma compounds and the metabolic regulation in Baijiu during brewing, which will be helpful for industrialization and the modern production of Baijiu.

A Direct-Writing Approach for Fabrication of CNT/Paper-Based Piezoresistive Pressure Sensors for Airflow Sensing.

Airflow sensor is a crucial component for monitoring environmental airflow conditions in many engineering fields, especially in the field of aerospace engineering. However, conventional airflow sensors have been suffering from issues such as complexity and bulk in structures, high cost in fabrication and maintenance, and low stability and durability. In this work, we developed a facile direct-writing method for fabricating a low-cost piezoresistive element aiming at high-performance airflow sensing, in which a commercial pen was utilized to drop solutions of single-walled carbon nanotubes onto tissue paper to form a piezoresistive sensing element. The encapsulated piezoresistive element was tested for electromechanical properties under two loading modes: one loading mode is the so-called pressure mode in which the piezoresistive element is pressed by a normal pressure, and another mode is the so-called bending mode in which the piezoresistive element is bended as a cantilever beam. Unlike many other developed airflow sensors among which the sensing elements are normally employed as cantilever beams for facing winds, we designed a fin structure to be incorporated with the piezoresistive element for airflow sensing; the main function of the fin is to face winds instead of the piezoresistive element, and subsequently transfer and enlarge the airflow pressure to the piezoresistive element for the normal pressure loading mode. With this design, the piezoresistive element can also be protected by avoiding experiencing large strains and direct contact with external airflows so that the stability and durability of the sensor can be maintained. Moreover, we experimentally found that the performance parameters of the airflow sensor could be effectively tuned by varying the size of the fin structure. When the fin sizes of the airflow sensors were 20 mm, 30 mm, and 40 mm, the detection limits and sensitivities of the fabricated airflow sensors were measured as 8.2 m/s, 6.2 m/s, 3.2 m/s, 0.0121 (m/s)-2, 0.01657 (m/s)-2, and 0.02264 (m/s)-2, respectively. Therefore, the design of the fin structure could pave an easy way for adjusting the sensor performance without changing the sensor itself toward different application scenarios.

Analysis of wireless power transmission system with negative impedance converter.

In this study, we analyze a resonant coupled wireless power transmission system with a negative impedance converter (NIC). The expressions for the output power of this system are obtained. The constraints of system parameter selection are determined according to the practical limitations of the NIC. The energy efficiency ratio (EER) is introduced to represent the relationship between the increase in system output power and the additional loss caused by the introduction of the NIC. The influence of the NIC on the EER was tested by changing the negative resistance. The experimental results show that the NIC reduces the loop impedance, increases the loop current, and improves the output power of the system. In addition, setting the appropriate parameters of the NIC can effectively increase the EER of resonant coupled radio power transmission by more than 4%.

Unraveling variation on the profile aroma compounds of strong aroma type of Baijiu in different regions by molecular matrix analysis and olfactory analysis.

Among 12 aroma types of Baijiu, the strong aroma type of Baijiu (Nongxiangxing Baijiu) is well received by customers for its rich and full aroma profile. According to the aroma characteristics of different geographical locations, Nongxiangxing Baijiu can be divided into Jianghuai, Sichuan and North categories. However, the reasons for the differences in Nongxiangxing Baijiu flavor in different regions are still unclear. Hence, representative brands (i.e., Gujinggong, Luzhou Laojiao and Banchengshaoguo) of Nongxiangxing Baijiu from three representative regions were chosen to explore their differences in profile aroma compounds. In this study, a total of 50, 41, 35 potential aroma compounds in Banchengshaoguo, Gujinggong, and Luzhou Laojiao samples were respectively identified by direct injection combined with gas chromatography-olfactometry/mass spectrometry (GC-O/MS). Among them, 18 aroma compounds were further recognized as important aroma compounds owing to their high flavor dilution (FD) value, Osme value, and odor activity value (OAV) ≥ 1. Moreover, the relationship between the above potential aroma compounds and the aroma profile of the three representative samples was analyzed by molecular matrix analysis. The results showed that various aroma compounds contributed differently to the flavor characteristics of Nongxiangxing Baijiu. In particular, 13 aroma compounds were tentatively defined as crucial profile aroma compounds due to their high aroma expression intensity and remarkable contribution to the flavor characteristics of Nongxiangxing Baijiu in different regions, and these crucial profile aroma compounds may be the reason for the difference in aroma profile of Nongxiangxing Baijiu from distinct regions.

Correction: Unraveling variation on the profile aroma compounds of strong aroma type of Baijiu in different regions by molecular matrix analysis and olfactory analysis.

[This corrects the article DOI: 10.1039/D1RA06073B.].

Dynamic modeling and characteristic analysis of piezoelectric rudder actuator.

In this note, dynamic equations of the piezoelectric rudder actuator are established using a numerical method, and the dynamic characteristics are analyzed. A simulation is performed using finite element software to verify the validity of the theory. The results show that an increase in axial force has significant amplification effects on the static displacement output of the bimorph and its rudder actuator, and the axial stiffness of the piezoelectric bimorph is evidently nonlinear against larger axial force. The response time of the rudder actuator is less affected by the axial force and remains in the order of milliseconds under the axial force of 0.85 times the buckling critical load.

Combination of doxorubicin liposomes with left atrial appendage radiofrequency catheter ablation to reduce post-ablation recovery of electrical conduction.

AIMS: To determine whether use of radiofrequency catheter ablation (RFCA) combined with intravenously administered liposomal doxorubicin (L-DOX) facilitates a reduction in the recovery of post-ablation electrical conduction. METHODS: Circumferential ablation was performed on the epicardial surface of the left atrial appendage (LAA) in New Zealand White rabbits, and L-DOX was then administered intravenously. Fluorescence spectrophotometry was used to assess reagent bio-distribution, while Western blots and immunohistochemistry were used to assess the localization of the apoptotic markers Bcl-2, Bax, and cleaved CASP3 in the LAA. Liver, kidney, and cardiac functions were also measured to evaluate the safety of this approach. RESULTS: At 1 week and 1 month after RFCA, a pacing electrocardiogram could not be detected in most of the rabbits that had received the combined RFCA and L-DOX therapy. L-DOX began to target the LAA on the second day after RFCA. L-DOX treatment increased the apoptosis of cardiomyocytes in the regions peripheral to the necrotic area induced by RFCA. Doxorubicin had some effect on liver and kidney function, but these effects were reversible and did not affect survival. CONCLUSION: The present results provide evidence that L-DOX treatment can reduce the recovery of electrical conduction after RFCA therapy owing to L-DOX-induced apoptosis of cardiomyocytes in the ablated area and the proximal transition zone of the LAA.