Efficacy of Polyethylene Glycol Electrolyte Powder Combined with Linaclotide for Colon Cleansing in Patients with Chronic Constipation undergoing colonoscopy: a Multi-centre, single-blinded, Randomized-Controlled Trial.

BACKGROUND AND AIMS: Constipation is an independent risk factor for poor bowel preparation. This study aimed to evaluate the bowel-cleansing efficacy and safety of polyethylene glycol (PEG) combined with linaclotide (lin) for colonoscopy in patients with chronic constipation. METHODS: This single-blinded, randomized, controlled and multicenter study was conducted from July 2021 to December 2022 at seven hospitals. Patients with chronic constipation who underwent colonoscopies were enrolled and randomly assigned to 4 groups with split -PEG regimens: 4L-PEG group, 4L-PEG+1d-Lin group, 3L-PEG+1d-Lin group, and 3L-PEG+3d-Lin group. The primary outcome was rates of adequate bowel preparation, defined as a total BBPS score ≥6 and a score ≥2 for each segment. Secondary outcomes were adverse effects, sleep quality, willingness to repeat the colonoscopy, adenoma detection rate, and polyp detection rate. RESULTS: 502 patients were enrolled. The rates of adequate bowel preparation (80.0% vs. 60.3%, P<0.001; 84.4% vs. 60.3%, P<0.001) and the total BBPS scores (6.90±1.28 vs. 6.00±1.61, P<0.001; 7.03±1.24 vs. 6.00±1.61, P<0.01) in 4L-PEG+1d-Lin group and 3L-PEG+3d-Lin group were superior to that in 4L-PEG group. Compared with 4L-PEG group, 4L-PEG+1d-Lin group (66.7% vs. 81.7%, P=0.008) and 3L-PEG+3d-Lin group (75.0% vs. 81.7%, P=0.224) had a lower percentage of mild adverse events. No statistically significant difference in willingness to repeat the colonoscopy, sleep quality, polyp detection rate, or adenoma detection rate was observed among groups. CONCLUSIONS: PEG combined with linaclotide might be an effective method for bowel preparation before colonoscopy in patients with chronic constipation.

Machine learning approaches reveal highly heterogeneous air quality co-benefits of the energy transition.

Estimating health benefits of reducing fossil fuel use from improved air quality provides important rationales for carbon emissions abatement. Simulating pollution concentration is a crucial step of the estimation, but traditional approaches often rely on complicated chemical transport models that require extensive expertise and computational resources. In this study, we develop a machine learning framework that is able to provide precise and robust annual average fine particle (PM2.5) concentration estimations directly from a high-resolution fossil energy use dataset. Applications of the framework with Chinese data reveal highly heterogeneous health benefits of avoiding premature mortality by reducing fossil fuel use in different sectors and regions in China with a mean of $19/tCO2 and a standard deviation of $38/tCO2. Reducing rural and residential coal use offers the highest co-benefits with a mean of $151/tCO2. Our findings prompt careful policy designs to maximize cost-effectiveness in the transition toward a carbon-neutral energy system.

Simultaneous removal of norfloxacin and chloramphenicol using cold atmospheric plasma jet (CAPJ): Enhanced performance, synergistic effect, plasma-activated water (PAW) contribution, mechanism and toxicity evaluation.

The extensive abuse and inadvertent discharge of various antibiotics into the environment has become a serious problem for posing a big threat to human health. In order to deal with this problem, we utilized cold atmospheric plasma jet (CAPJ) to treat two different antibiotics, namely, norfloxacin and chloramphenicol, and investigated the efficiencies and corresponding mechanisms for removing the mixed antibiotics. In the application of the CAPJ technique, we made use of not only the direct plasma processing, but also the indirect plasma-activated water (PAW) treatment. The efficiency for mixed antibiotics treatment was considerably enhanced as compared to the efficiency for treatment of single antibiotics. The contributions from the CAPJ-induced reactive oxygen/nitrogen species (RONS) were examined, showing that ·OH and 1O2 played a major role in the degradation of norfloxacin and chloramphenicol in the direct plasma treatment, while 1O2 played a major role in the PAW treatment. The bio-toxicity evaluation was also provided to verify the ecological safety of the CAPJ treatment. As such, this work has not only showed the effectiveness of CAPJ treatment of mixed antibiotics, but also elucidated the mechanisms for the enhanced treatment efficiency, which may provide a new solution for treatment of antibiotics in the environment.

Comparing modelling approaches for the estimation of government intervention effects in COVID-19: Impact of voluntary behavior changes.

The efficacy of government interventions in epidemic has become a hot subject since the onset of COVID-19. There is however much variation in the results quantifying the effects of interventions, which is partly related to the varying modelling approaches employed by existing studies. Among the many factors affecting the modelling results, people's voluntary behavior change is less examined yet likely to be widespread. This paper therefore aims to analyze how the choice of modelling approach, in particular how voluntary behavior change is accounted for, would affect the intervention effect estimation. We conduct the analysis by experimenting different modelling methods on a same data set composed of the 500 most infected U.S. counties. We compare the most frequently used methods from the two classes of modelling approaches, which are Bayesian hierarchical model from the class of computational approach and difference-in-difference from the class of natural experimental approach. We find that computational methods that do not account for voluntary behavior changes are likely to produce larger estimates of intervention effects as assumed. In contrast, natural experimental methods are more likely to extract the true effect of interventions by ruling out simultaneous behavior change. Among different difference-in-difference estimators, the two-way fixed effect estimator seems to be an efficient one. Our work can inform the methodological choice of future research on this topic, as well as more robust re-interpretation of existing works, to facilitate both future epidemic response plans and the science of public health.

Architecture design of cucurbit crops for enhanced productivity by a natural allele.

Increasing production efficiency is a top priority in agriculture. Optimal plant architecture is the biological basis of dense planting, high crop yield and labour cost savings, and is thus critical for improving agricultural productivity. In cucurbit crops, most species have elongated internodes, but the path to architecture improvement is still not clear. Here we identified a pumpkin accession with a dominant bushy trait, and found that the associated Bush locus harbours a cucurbit-conserved cis-regulatory element in the 5' untranslated region of a transcription factor gene YABBY1. In cucurbit crops, various B-region deletions enhance the translation of YABBY1, with consequent proportional suppression of stem length in a dose-dependent manner. Depending on different cultivation patterns, the precise deployment of these alleles has significant effects on yield improvement or labour cost saving. Our findings demonstrate that the engineering of the YABBY1 B-region is an efficient strategy to customize plant architecture in cucurbit crops.

Detecting aerosol backscattering coefficient across the whole troposphere by the sidescattering lidar system with three CCD cameras.

Due to geometric overlap factor, the backscattering lidar is not suitable to detect atmospheric characteristics near the ground. A new sidescattering lidar system consisting of three CCD cameras and one CW laser is developed for the first time to measure the profiles of the backscattering coefficient of atmospheric aerosols across the whole troposphere, which has no detection blind zone near the ground. The aerosol relative phase function was detected by its horizontal CCD channel. The vertical distribution of aerosol backscattering coefficient across the whole troposphere was observed by the other two CCD cameras of vertical channel. The reasons for choosing three CCD cameras and their respective functions are analyzed in detail. Comparative experiments and continuous observations indicate that the new sidescattering lidar system including three CCD cameras is simple in structure and reliable in performance with low cost as well.

Distinctions Between Fecal and Intestinal Mucosal Microbiota in Subgroups of Irritable Bowel Syndrome.

BACKGROUND AND AIMS: Recent studies have shown that changes in the intestinal microbiota contribute to the pathogenesis of irritable bowel syndrome (IBS). This study aimed to investigate the characteristics of the fecal and intestinal mucosal microbiota in IBS patients, and the correlation between microbiota and clinical manifestations. METHODS: Fecal and intestinal mucosal samples were collected from 14 constipation-predominant IBS (IBS-C) patients, 20 diarrhea-predominant IBS (IBS-D) patients, and 20 healthy controls (HCs). 16S rRNA gene sequencing and fluorescence in situ hybridization were used for the analysis of samples. RESULTS: Community richness and diversity of the fecal microbiota in IBS patients were significantly reduced compared with the HCs. The mucosal samples in IBS patients showed decreased Bifidobacterium and increased Bacteroides caccae compared with HCs; Eubacterium and Roseburia were decreased in IBS-C patients and increased in IBS-D patients. A comparison of the fecal and mucosal microbiota in IBS patients showed significantly increased Bifidobacterium in fecal samples and a decrease in mucosal samples in IBS-C patients; Bacteroides caccae and Roseburia were significantly reduced in fecal samples and increased in mucosal samples of IBS patients. A correlation between microbiota and clinical manifestations in IBS patients showed that Bacteroides caccae and Roseburia in fecal samples and Bifidobacterium and Eubacterium in mucosal samples were associated with abdominal pain and distention. CONCLUSIONS: Distinct differences exist between the fecal and intestinal mucosal microbiota in IBS patients, with the changes in the latter appearing more consistent with the pathophysiology of IBS. Changes in intestinal microbiota were associated with the clinical manifestations in IBS.

Study of detoxification of methyl parathion by dielectric barrier discharge (DBD) non-thermal plasma at gas-liquid interface：mechanism and bio-toxicity evaluation.

Methyl parathion (MP) as an organophosphorus pesticide has been used in the control of agricultural pests and diseases. Due to its high toxicity and persistence in the environment, MP may pose threat to human health when it is released into environmental water. For MP treatment, people have found that oxidative degradation of MP may generate some intermediates which are more toxic than MP itself, such as methyl paraoxon. Herein, we proposed a new method of applying dielectric barrier discharge (DBD) non-thermal plasma technology to treat MP in aqueous solution, and investigated the influences of different gases, pH value, discharge voltage/power, and main active species on the MP removal efficiency. In particular, the safety of DBD treatment was concerned with analysis of the biological toxicity of the byproducts from the DBD oxidation, and the DBD-induced degradation together with the involved mechanism was explored therein. The results showed that the production of toxic intermediates could be effectively suppressed or avoided under certain treatment conditions. As such, this work demonstrates that the proper application of DBD plasma technology with necessary caution can detoxify methyl parathion effectively, and also provides a practical guide for low-temperature plasma application in treatment of various organophosphorus pesticides in agricultural wastewater.

Introduction of a Novel, Continuous, Noninvasive Estimation of Intracranial Pressure and Cerebral Perfusion Pressure Based on Tympanic Membrane Temperature.

OBJECTIVE: Hydrocephalus is a common but potentially life-threatening condition. However, valve malfunction makes further diagnosis difficult. Thus, we tried to develop a noninvasive method to detect the hydrocephalus intracranial pressure (ICP) during routine follow-up. METHODS: In group I, the patient was recruited because a spinal tap test was necessary for either disease diagnosis or treatment. In group II, patients were diagnosed with high ICP hydrocephalus and received shunt surgery. The tympanic membrane temperatures (TMTs) were recorded and plotted against the spinal tap pressure (STP) and shunt valve pressures. RESULTS: All patients in group I showed an above-normal STP (from 180 to 400 mm H2O). The STP presents with an inverted U-shaped curve when it is plotted against TMT (R2 = 0.9). When the STP was 286.1 mm H2O, the TMT approached its peak value, which was 38.61°C (101.5°F). However, when ICP was in the normal range (50-200 mm H2O), the TMT correlated with ICP in a linear regression model (R2 = 0.69; P < 0.001). In addition, the cerebral perfusion pressure (CPP) was calculated and plotted against TMT. The TMT-CPP was also shown as a parabola (R2 = 0.74). Based on the TMT-ICP algorithm, we invented a noninvasive ICP monitor system, which performs in a manner comparable to the Codman ICP Transducer (R2 = 0.9; P < 0.01). CONCLUSIONS: Both Y-Jiang TMT-ICP and TMT-CPP algorithms are useful to monitor the shunt outcomes and identify potential shunt failure. More importantly, these algorithms open the possibility for the rational acquisition of ICP and CPP noninvasively.

Graph-based pan-genome reveals structural and sequence variations related to agronomic traits and domestication in cucumber.

Structural variants (SVs) represent a major source of genetic diversity and are related to numerous agronomic traits and evolutionary events; however, their comprehensive identification and characterization in cucumber (Cucumis sativus L.) have been hindered by the lack of a high-quality pan-genome. Here, we report a graph-based cucumber pan-genome by analyzing twelve chromosome-scale genome assemblies. Genotyping of seven large chromosomal rearrangements based on the pan-genome provides useful information for use of wild accessions in breeding and genetic studies. A total of ~4.3 million genetic variants including 56,214 SVs are identified leveraging the chromosome-level assemblies. The pan-genome graph integrating both variant information and reference genome sequences aids the identification of SVs associated with agronomic traits, including warty fruits, flowering times and root growth, and enhances the understanding of cucumber trait evolution. The graph-based cucumber pan-genome and the identified genetic variants provide rich resources for future biological research and genomics-assisted breeding.

Targeted creating new mutants with compact plant architecture using CRISPR/Cas9 genome editing by an optimized genetic transformation procedure in cucurbit plants.

Fruits and vegetables in the Cucurbitaceae family contribute greatly to the human diet, for example, cucumber, melon, watermelon and squash. The widespread use of genome editing technologies has greatly accelerated the functional characterization of genes as well as crop improvement. However, most economically important cucurbit plants, including melon and squash, remain recalcitrant to standard Agrobacterium tumefaciens-mediated transformation, which limits the effective use of genome editing technology. In this study, we describe the "optimal infiltration intensity" strategy to establish an efficient genetic transformation system for melon and squash. We harnessed the power of this method to target homologs of the ERECTA family of receptor kinase genes and created alleles resulting in a compact plant architecture with shorter internodes in melon, squash and cucumber. The optimized transformation method presented here allows stable CRISPR/Cas9-mediated mutagenesis and will lay a solid foundation for functional gene manipulation in cucurbit crops.

Infectiousness of places - Impact of multiscale human activity places in the transmission of COVID-19.

COVID-19 raises attention to epidemic transmission in various places. This study analyzes the transmission risks associated with human activity places at multiple scales, including different types of settlements and eleven types of specific establishments (restaurants, bars, etc.), using COVID-19 data in 906 urban areas across four continents. Through a difference-in-difference approach, we identify the causal effects of activities at various places on epidemic transmission. We find that at the micro-scale, though the transmission risks at different establishments differ across countries, sports, entertainment, and catering establishments are generally more infectious. At the macro-scale, contradicting common beliefs, it is consistent across countries that transmission does not increase with settlement size and density. It is also consistent that specific establishments play a lesser role in transmission in larger settlements, suggesting more transmission happening elsewhere. These findings contribute to building a system of knowledge on the linkage between places, human activities, and disease transmission.

Degradation of tetracycline by atmospheric-pressure non-thermal plasma: Enhanced performance, degradation mechanism, and toxicity evaluation.

Tetracycline is a common antibiotic and is often carelessly released into the natural environment, thus constantly posing potential threats to the environment. Currently, due to lack of effective methods to remove it from the environmental water system, researchers are still exploring new ways to deal with tetracycline. In this work, we employed atmospheric-pressure non-thermal plasma (NTP) to treat tetracycline in water and investigated the involved degradation mechanism. The enhanced degradation efficiency was acquired and investigated, and the degradation mechanism by the plasma-generated active species were explored. The tetracycline degradation pathways via especially the interactions with plasma-generated hydroxyl radical and ozone were examined by virtue of UV spectroscopy, three-dimensional fluorescence spectroscopy, high performance liquid chromatography-mass spectrometry (HPLC-MS), together with the assistance of theoretical simulations. Moreover, the toxicological evaluation of NTP treatment of tetracycline was also provided, which confirmed that the biological toxicity of tetracycline degradation products was negligible. Therefore, this work provides not only the effective way of treating antibiotics by engineered plasma technology, but also the insights into the mechanisms of degradation of antibiotics by NTP.

The Prevalence, Popular Trends, and Associated and Predictive Factors of Non-Obese Fatty Liver Disease.

Background and Aims: There are few studies on non-obese fatty liver disease, the aims of this study was to analyze its prevalence, popular trends, and associated and predictive factors, so as to provide reference for its prevention and treatment. Methods: Individuals with complete data of body mass index, sex, age, and abdominal ultrasound in Karamay Central Hospital from 2009 to 2016 were selected to analyze the prevalence and popular trends of non-obese fatty liver disease (body mass index <24 kg/m2), and associated and predictive factors. Results: Between 2009 and 2016, a total of 191,555 medical check-ups were included. The prevalence of non-obese fatty liver disease increased from 1.9% to 5.1% among general medical examinants (P<0.001), increased from 4.6% to 11.7% in non-obese individuals (P<0.001). Compared with the non-obese control group, the levels of age, body mass index, blood pressure, fasting blood glucose, triglycerides, total cholesterol and uric acid in the non-obese fatty liver group were higher (P<0. 05). Even among non-obese subjects, elevated body mass index was associated with a 0.63-fold increased risk for non-obese fatty liver disease (P<0.001, odds ratio=1.63, 95% confidence interval 1.54-1.72) for every one-unit increase in body mass index. The most common abnormal indicator of non-obese fatty liver disease was elevated triglycerides (44.2%), which was also the best predictor of non-obese fatty liver disease (area under the curve =0.795) in non-obese physical examinators. Conclusions: The prevalence of non-obese fatty liver disease was high and increasing rapidly in Karamay. Triglycerides is the best predictor of non-obese fatty liver in non-obese physical examinators.

Calcifying pseudoneoplasms of the neuraxis (CAPNON). A case report.

Calcifying pseudoneoplasms of the neuraxis (CAPNON) are rare, slow-growing, benign lesions occurring throughout the neuroaxis that are frequently misdiagnosed and overlooked by clinicians. Here, we report a case of a 56-year-old woman who presented with a history of recurrent headache for the previous six years. Magnetic resonance imaging (MRI) revealed a 2.3-cm-sized solid mass in the right frontal lobe that was surrounded by marked edematous areas. The lesion demonstrated dense calcification and avid enhancement. The lesion was initially diagnosed as oligodendroglioma, and then found to be CAPNON based on histopathology of a surgically resected tissue. Genetic analysis revealed a nonsense mutation in the CUL4B gene. The patient's condition appeared to reflect a reactive, rather than neoplastic, process. Clinicians should be prepared to detect such pseudotumors histopathologically in order to avoid unnecessary differential tests of neoplastic or infectious diseases, as well as potentially harmful therapies.

The association of traumatic brain injury, gut microbiota and the corresponding metabolites in mice.

BACKGROUND: Traumatic Brain Injury (TBI) present a significant burden to global health. Close association and mutual regulation exist between the brain and gut microbiota. In addition, metabolites may play an important role as intermediary mediators of the brain and gut microbiota. Consequently, the study sought to investigate the alterations in gut microbiota and metabolites after TBI and conducted a comprehensive analysis of the correlation between gut microbiota and metabolites after TBI in mice. METHODS: Changes in intestinal microbiota and metabolites in mice after moderate or severe traumatic brain injury were detected through 16S rDNA sequencing and the non-target LC-MS technology. Additionally, Pearson correlation analysis was used to explore the association between the microbiota and metabolites. RESULTS: TBI was able to change the composition of intestinal microbiota, resulting to a decrease in microbial diversity in the intestinal tract (sham vs sTBI: 8.35 ± 0.12 vs 7.71 ± 0.5, p < 0.01; sTBI vs mTBI: 7.71 ± 0.5 vs 8.25 ± 0.34, p < 0.05). The results also showed that TBI could change the types and abundance of metabolites (723 in mTBI and sham groups; 1221 in sTBI and sham groups; 324 in mTBI and sTBI groups). Moreover, some of the altered gut metabolites were significantly correlated with part of the altered gut microbes after TBI. CONCLUSIONS: TBI significantly changed intestinal microbiota as well as metabolites. Some of the altered microbiota and metabolites had a significant association. The results from this study provide information that paves way for future studies utilizing the brain gut axis theory in the diagnosis and treatment of TBI.

Knockdown of TRIM15 inhibits the proliferation, migration and invasion of esophageal squamous cell carcinoma cells through inactivation of the Wnt/ß-catenin signaling pathway.

TRIM15 is a member of tripartite motif-containing protein (TRIM) protein family, which plays important roles in several cancers. The aim of the present study was to evaluate the role of TRIM15 in esophageal squamous cell carcinoma (ESCC). Our results showed that TRIM15 was upregulated in human ESCC tissues and cell lines. In vitro studies showed that knockdown of TRIM15 significantly inhibited the proliferation, migration, and invasion of ESCC cells. Knockdown of TRIM15 caused a significant increase in E-cadherin expression, as well as decreases in expression of N-cadherin and Vimentin proteins. Moreover, in vivo assay proved that tumor growth was suppressed by knockdown of TRIM15. Furthermore, the protein expression levels of ß-catenin, C-myc, and CyclinD1 were markedly decreased in sh-TRIM15-infected ESCC cells. Additionally, treatment with LiCl reversed the inhibitory effects of TRIM15 knockdown on ESCC cells. In conclusion, these findings indicated that knockdown of TRIM15 blocked the growth and metastasis of ESCC in part through inhibiting the Wnt/ß-catenin signaling pathway. Thus, TRIM15 might serve as a promising therapeutic target for ESCC.

Regulation of plant architecture by a new histone acetyltransferase targeting gene bodies.

Axillary meristem development determines both plant architecture and crop yield; this critical process is regulated by the PROLIFERATING CELL FACTORS (TCP) family of transcription factors. Although TCP proteins bind primarily to promoter regions, some also target gene bodies for expression activation. However, the underlying regulatory mechanism remains unknown. Here we show that TEN, a TCP from cucumber (Cucumis sativus L.), controls the identity and mobility of tendrils. Through its C terminus, TEN binds at intragenic enhancers of target genes; its N-terminal domain functions as a non-canonical histone acetyltransferase (HAT) to preferentially act on lysine 56 and 122 of the histone H3 globular domain. This HAT activity is responsible for chromatin loosening and host-gene activation. The N termini of all tested CYCLOIDEA and TEOSINTE BRANCHED 1-like TCP proteins contain an intrinsically disordered region; despite their sequence divergence, they have conserved HAT activity. This study identifies a non-canonical class of HATs and provides a mechanism by which modification at the H3 globular domain is integrated with the transcription process.

RP11-81H3.2 promotes gastric cancer progression through miR-339-HNRNPA1 interaction network.

Recent studies have demonstrated that various long non-coding RNAs (lncRNAs) participate in the gastric cancer (GC) development and metastasis. Some lncRNAs exert their regulatory function by interacting with microRNAs. Here we identified a novel lncRNA RP11-81H3.2 that was highly expressed in the GC tissue and cell lines. RP11-81H3.2 knockdown significantly inhibited the proliferation, migration, and invasion of GC cells. Mechanistically, we demonstrated that RP11-81H3.2 directly interacted with miR-339 while miR-339 regulated the HNRNPA1 expression by targeting HRRNPA1 3'-UTR. RP11-81H3.2-miR-339-HNRNPA1 interaction network regulated the GC cell proliferation, migration, and invasion. Moreover, our results confirmed that RP11-81H3.2 knockdown suppressed the tumor growth of GC in a xenograft model in vivo. In summary, the results suggest that RP11-81H3.2 functions as an oncogene in GC and could be utilized as a promising diagnosis and therapeutic marker for GC treatment.

Genome-wide Target Mapping Shows Histone Deacetylase Complex1 Regulates Cell Proliferation in Cucumber Fruit.

Histone deacetylase (HDAC) proteins participate in diverse and tissue-specific developmental processes by forming various corepressor complexes with different regulatory subunits. An important HDAC machinery hub, the Histone Deacetylase Complex1 (HDC1) protein, participates in multiple protein-protein interactions and regulates organ size in plants. However, the mechanistic basis for this regulation remains unclear. Here, we identified a cucumber (Cucumis sativus) short-fruit mutant (sf2) with a phenotype that includes repressed cell proliferation. SF2 encodes an HDC1 homolog, and its expression is enriched in meristematic tissues, consistent with a role in regulating cell proliferation through the HDAC complex. A weak sf2 allele impairs HDAC targeting to chromatin, resulting in elevated levels of histone acetylation. Genome-wide mapping revealed that SF2 directly targets and promotes histone deacetylation associated with key genes involved in multiple phytohormone pathways and cell cycle regulation, by either directly repressing or activating their expression. We further show that SF2 controls fruit cell proliferation through targeting the biosynthesis and metabolism of cytokinin and polyamines. Our findings reveal a complex regulatory network of fruit cell proliferation mediated by HDC1 and elucidate patterns of HDC1-mediated regulation of gene expression.