Whether probiotics are beneficial at all stages of treatment in inflammatory bowel disease or superior to placebo remains controversial.
Two reviewers independently selected randomized controlled ...trials comparing probiotics with controls in inflammatory bowel disease and extracted data related to remission/response rates, relapse rates, and adverse events. Subanalyses were also performed.
Twenty-three randomized controlled trials with a total of 1763 participants met the inclusion criteria. From the meta-analysis, probiotics significantly increase the remission rates in patients with active ulcerative colitis (UC) (P = 0.01, risk ratio RR = 1.51). The remission rates were significantly higher in patients with active UC treated with probiotics than placebo (P < 0.0001, RR = 1.80). Unfortunately, subgroup analysis found that only VSL#3 significantly increased the remission rates compared with controls in patients with active UC (P = 0.004, RR = 1.74). Interestingly, VSL#3 (P < 0.00001, RR = 0.18) also significantly reduced the clinical relapse rates for maintaining remission in patients with pouchitis. No significantly different adverse events were detected between probiotics and controls in the treatment of UC (P = 0.94, RR = 0.99) or CD (P = 0.33, RR = 0.87).
Administration of probiotics results in additional benefit in inducing remission of patients with UC. VSL#3 are beneficial for maintaining remission in patients with pouchitis. And, probiotics can provide the similar effect as 5-aminosalicylic acid on maintaining remission of UC, although no additional adverse events presented.
The Caco-2 cell monolayer model is a popular surrogate in predicting the in vitro human intestinal permeability of a drug due to its morphological and functional similarity with human enterocytes. A ...quantitative structure-property relationship (QSPR) study was carried out to predict Caco-2 cell permeability of a large data set consisting of 1272 compounds. Four different methods including multivariate linear regression (MLR), partial least-squares (PLS), support vector machine (SVM) regression and Boosting were employed to build prediction models with 30 molecular descriptors selected by nondominated sorting genetic algorithm-II (NSGA-II). The best Boosting model was obtained finally with R(2) = 0.97, RMSEF = 0.12, Q(2) = 0.83, RMSECV = 0.31 for the training set and RT(2) = 0.81, RMSET = 0.31 for the test set. A series of validation methods were used to assess the robustness and predictive ability of our model according to the OECD principles and then define its applicability domain. Compared with the reported QSAR/QSPR models about Caco-2 cell permeability, our model exhibits certain advantage in database size and prediction accuracy to some extent. Finally, we found that the polar volume, the hydrogen bond donor, the surface area and some other descriptors can influence the Caco-2 permeability to some extent. These results suggest that the proposed model is a good tool for predicting the permeability of drug candidates and to perform virtual screening in the early stage of drug development.
The ureolytic bacterium Sporosarcina pasteurii is well-known for its capability of microbially induced calcite precipitation (MICP), representing a great potential in constructional engineering and ...material applications. However, the molecular mechanism for its biomineralization remains unresolved, as few studies were carried out.
The addition of urea into the culture medium provided an alkaline environment that is suitable for S. pasteurii. As compared to S. pasteurii cultivated without urea, S. pasteurii grown with urea showed faster growth and urease production, better shape, more negative surface charge and higher biomineralization ability. To survive the unfavorable growth environment due to the absence of urea, S. pasteurii up-regulated the expression of genes involved in urease production, ATPase synthesis and flagella, possibly occupying resources that can be deployed for MICP. As compared to non-mineralizing bacteria, S. pasteurii exhibited more negative cell surface charge for binding calcium ions and more robust cell structure as nucleation sites. During MICP process, the genes for ATPase synthesis in S. pasteurii was up-regulated while genes for urease production were unchanged. Interestingly, genes involved in flagella were down-regulated during MICP, which might lead to poor mobility of S. pasteurii. Meanwhile, genes in fatty acid degradation pathway were inhibited to maintain the intact cell structure found in calcite precipitation. Both weak mobility and intact cell structure are advantageous for S. pasteurii to serve as nucleation sites during MICP.
Four factors are demonstrated to benefit the super performance of S. pasteurii in MICP. First, the good correlation of biomass growth and urease production of S. pasteurii provides sufficient biomass and urease simultaneously for improved biomineralization. Second, the highly negative cell surface charge of S. pasteurii is good for binding calcium ions. Third, the robust cell structure and fourth, the weak mobility, are key for S. pasteurii to be nucleation sites during MICP.
Few-layer black phosphorus (BP), as the most alluring graphene analogue owing to its similar structure as graphene and thickness dependent direct band-gap, has now triggered a new wave of research on ...two-dimensional (2D) materials based photonics and optoelectronics. However, a major obstacle of practical applications for few-layer BPs comes from their instabilities of laser-induced optical damage. Herein, we demonstrate that, few-layer BPs, which was fabricated through the liquid exfoliation approach, can be developed as a new and practical saturable absorber (SA) by depositing few-layer BPs with microfiber. The saturable absorption property of few-layer BPs had been verified through an open-aperture z-scan measurement at the telecommunication band. The microfiber-based BP device had been found to show a saturable average power of ~4.5 mW and a modulation depth of 10.9%, which is further confirmed through a balanced twin detection measurement. By integrating this optical SA device into an erbium-doped fiber laser, it was found that it can deliver the mode-locked pulse with duration down to 940 fs with central wavelength tunable from 1532 nm to 1570 nm. The prevention of BP from oxidation through the "lateral interaction scheme" owing to this microfiber-based few-layer BP SA device might partially mitigate the optical damage problem of BP. Our results not only demonstrate that black phosphorus might be another promising SA material for ultrafast photonics, but also provide a practical solution to solve the optical damage problem of black phosphorus by assembling with waveguide structures such as microfiber.
Visual impairment (VI) seriously affects the quality of life of the older adults. It is important to formulate appropriate health management strategies for the older adults with VI to help delay the ...disease development and progression, and improve life quality. The aim of this study was to understand the demand preference for health management services of the older adults with VI, and to provide a reference for the development of future health management strategies in this population.
The conjoint analysis method was used to analyze demand preferences for health management services of the older adults with VI. 11 keywords were extracted after literature analyzed, 6 keywords were selected as the attributes of health management strategy after expert discussion and the level of each attribute was determined. Then 18 representative virtual health management strategies were formed by combination of different attribute levels through orthogonal design, and older adults with VI were asked to score. A total of 334 older adults with VI who attended the ophthalmology department of the First Affiliated Hospital of China Medical University and the Fourth People's Hospital of Shenyang from February 27, 2021 to June 30, 2021were enrolled in this study by stratified sampling. Of the 334 included people, 80 had grade 1 VI, 80 had grade 2 VI, 84 had grade 3 VI, and 90 had grade 4 VI.
The relative importance of health management services ranked by older adults with VI was continuing care (24.033%), visual aid application (19.61%), health education (16.241%), preventive healthcare (15.667%), safety management (12.757%), and rehabilitation training (11.392%). The utility values of each level of continuing care, safety management and preventive healthcare were positive, whereas the utility values of each level of visual aid application, health education and rehabilitation training were negative. The relative importance and utility values of health management services were different for the older adults with different grades of VI.
From the whole group, the older adults with VI have a higher preference for continuing care and a lower preference for rehabilitation training. The preference of the older adults with different grades of VI is different, so medical workers can formulate corresponding health management strategies according to their different demand preferences, and carry out hierarchical health management. Services that they preferred should be satisfied as much as possible in the health management strategy, while the reasons for the services with lower preference can be explored and make targeted improvement to meet the demand preferences of them.
Background Monoclonal antibodies targeting programmed death ligand 1 (PD-L1) signaling currently approved for defective mismatch repair (dMMR)/microsatellite instability high (MSI-H) tumors must be ...delivered by intravenous infusion. Envafolimab, a humanized single-domain anti-PD-L1 antibody fused to an Fc fragment, represents a potential advance because it can be conveniently administered subcutaneously. Methods This open-label, single-arm, phase 2 study evaluated the efficacy and safety of envafolimab in patients with previously treated advanced dMMR/MSI-H tumors from 25 clinical sites across China. Adults with histologically confirmed locally advanced or metastatic malignant dMMR/MSI-H solid tumors received weekly 150 mg subcutaneous envafolimab injections in a 28-day treatment cycle. The primary efficacy endpoint was the objective response rate (assessed by a blinded independent review committee). Secondary efficacy outcomes were disease control rate, duration of response, progression-free survival, and overall survival. Results One hundred and three patients (65 with colorectal cancer, 18 with gastric cancer, and 20 with other solid tumors) were enrolled. Median follow-up was 11.5 months. The objective response rate was 42.7% (95% confidence interval CI 33.0-52.8), and the disease control rate was 66.0% (95% CI 56.0-75.1). Median duration of response was not reached; the duration of response rate at 12 months was 92.2% (95% CI 77.5-97.4). Median progression-free survival was 11.1 months (95% CI 5.5 to not evaluable). Overall survival at 12 months was 74.6% (95% CI 64.7-82.1). Sixteen patients (16%) had at least one grade 3 or 4 related treatment-emergent adverse event. No grade 5 treatment-emergent adverse events related to envafolimab were reported. Injection site reactions, all grade 1-2, were reported in nine patients (9%), but there were no infusion reactions. Eight patients (8%) had grade 3 or 4 immune-related adverse events. Conclusions This is the first pivotal phase 2 study to examine the efficacy and safety of a single-domain immune checkpoint antibody in the treatment of cancer. Envafolimab was effective and had acceptable safety in the treatment of previously treated advanced dMMR/MSI-H solid tumors. As the first single-domain PD-L1-targeting antibody administered by rapid subcutaneous injection, envafolimab has the potential to be a significant advance in the treatment of cancer. Trial registration ClinicalTrials.gov, NCT03667170. Registered 10 September 2018--Retrospectively registered, Keywords: Envafolimab, PD-L1, dMMR/MSI-H, Subcutaneous injection
Microglia-associated neuroinflammation plays an important role in the pathophysiology of ischemic stroke. Microglial activation and polarization, and the inflammatory response mediated by these cells ...play important roles in the development, progression and outcome of brain injury after ischemic stroke. Currently, there is no effective strategy for treating ischemic stroke in clinical practice. Therefore, it is clinically important to study the role and regulation of microglia in stroke. In this review, we discuss the involvement of microglia in the neuroinflammatory process in ischemic stroke, with the aim of providing a better understanding of the relationship between ischemic stroke and microglia.
Three new species of Philagra Stål, P. bimaculata sp. nov., P. fuscofasciata sp. nov. and P. straminea sp. nov. are described and illustrated from China with P. bimaculata sp. nov. also recorded from ...Bangladesh. Morphological descriptions and structural illustrations of the new species are provided with distributional data given. Scanning electron micrographs of antennal sensilla of P. bimaculata sp. nov. and P. straminea sp. nov. and sensilla on rostral apex of P. bimaculata sp. nov. are provided for the first time.
Background
With the increasing development of biotechnology and informatics technology, publicly available data in chemistry and biology are undergoing explosive growth. Such wealthy information in ...these data needs to be extracted and transformed to useful knowledge by various data mining methods. Considering the amazing rate at which data are accumulated in chemistry and biology fields, new tools that process and interpret large and complex interaction data are increasingly important. So far, there are no suitable toolkits that can effectively link the chemical and biological space in view of molecular representation. To further explore these complex data, an integrated toolkit for various molecular representation is urgently needed which could be easily integrated with data mining algorithms to start a full data analysis pipeline.
Results
Herein, the python library
PyBioMed
is presented, which comprises functionalities for online download for various molecular objects by providing different IDs, the pretreatment of molecular structures, the computation of various molecular descriptors for chemicals, proteins, DNAs and their interactions.
PyBioMed
is a feature-rich and highly customized python library used for the characterization of various complex chemical and biological molecules and interaction samples. The current version of
PyBioMed
could calculate 775 chemical descriptors and 19 kinds of chemical fingerprints, 9920 protein descriptors based on protein sequences, more than 6000 DNA descriptors from nucleotide sequences, and interaction descriptors from pairwise samples using three different combining strategies. Several examples and five real-life applications were provided to clearly guide the users how to use
PyBioMed
as an integral part of data analysis projects. By using
PyBioMed
, users are able to start a full pipelining from getting molecular data, pretreating molecules, molecular representation to constructing machine learning models conveniently.
Conclusion
PyBioMed
provides various user-friendly and highly customized APIs to calculate various features of biological molecules and complex interaction samples conveniently, which aims at building integrated analysis pipelines from data acquisition, data checking, and descriptor calculation to modeling.
PyBioMed
is freely available at
http://projects.scbdd.com/pybiomed.html
.
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