Episymbiotic Saccharibacteria TM7x modulates the susceptibility of its host bacteria to phage infection and promotes their coexistence.

Bacteriophages (phages) play critical roles in modulating microbial ecology. Within the human microbiome, the factors influencing the long-term coexistence of phages and bacteria remain poorly investigated. Saccharibacteria (formerly TM7) are ubiquitous members of the human oral microbiome. These ultrasmall bacteria form episymbiotic relationships with their host bacteria and impact their physiology. Here, we showed that during surface-associated growth, a human oral Saccharibacteria isolate (named TM7x) protects its host bacterium, a Schaalia odontolytica strain (named XH001) against lytic phage LC001 predation. RNA-Sequencing analysis identified in XH001 a gene cluster with predicted functions involved in the biogenesis of cell wall polysaccharides (CWP), whose expression is significantly down-regulated when forming a symbiosis with TM7x. Through genetic work, we experimentally demonstrated the impact of the expression of this CWP gene cluster on bacterial-phage interaction by affecting phage binding. In vitro coevolution experiments further showed that the heterogeneous populations of TM7x-associated and TM7x-free XH001, which display differential susceptibility to LC001 predation, promote bacteria and phage coexistence. Our study highlights the tripartite interaction between the bacterium, episymbiont, and phage. More importantly, we present a mechanism, i.e., episymbiont-mediated modulation of gene expression in host bacteria, which impacts their susceptibility to phage predation and contributes to the formation of "source-sink" dynamics between phage and bacteria in biofilm, promoting their long-term coexistence within the human microbiome.

Exploring the correlation of metabolites changes and microbial succession in solid-state fermentation of Sichuan Sun-dried vinegar.

BACKGROUND: The traditional Sichuan Sun-dried vinegar (SSV) with unique flavor and taste is believed to be generated by the solid-state fermentation craft. However, how microorganisms and their metabolites change along with fermentation has not yet been explored. RESULTS: In this study, our results demonstrated that the middle and late stages of SSV fermentation were the periods showing the largest accumulation of organic acids and amino acids. Furthermore, in the bacterial community, the highest average relative abundance was Lactobacillus (ranging from 37.55 to 92.50%) in all fermentation stages, while Acetobacters ranked second position (ranging from 20.15 to 0.55%). The number of culturable lactic acid bacteria is also increased during fermentation process (ranging from 3.93 to 8.31 CFU/g). In fungal community, Alternaria (29.42%), Issatchenkia (37.56%) and Zygosaccharomyces (69.24%) were most abundant in different fermentation stages, respectively. Interestingly, Zygosaccharomyces, Schwanniomyces and Issatchenkia were first noticed as the dominant yeast genera in vinegar fermentation process. Additionally, spearman correlation coefficients exhibited that Lactobacillus, Zygosaccharomyces and Schwanniomyces were significant correlation with most metabolites during the fermentation, implying that these microorganisms might make a significant contribution to the flavor formation of SSV. CONCLUSION: The unique flavor of SSV is mainly produced by the core microorganisms (Lactobacillus, Zygosaccharomyces and Schwanniomyces) during fermentation. This study will provide detailed information related to the structure of microorganism and correlation between changes in metabolites and microbial succession in SSV. And it will be very helpful for proposing a potential approach to monitor the traditional fermentation process.

Emergence of Polarization in Coevolving Networks.

Polarization is a ubiquitous phenomenon in social systems. Empirical studies document substantial evidence for opinion polarization across social media, showing a typical bipolarized pattern devising individuals into two groups with opposite opinions. While coevolving network models have been proposed to understand polarization, existing works cannot generate a stable bipolarized structure. Moreover, a quantitative and comprehensive theoretical framework capturing generic mechanisms governing polarization remains unaddressed. In this Letter, we discover a universal scaling law for opinion distributions, characterized by a set of scaling exponents. These exponents classify social systems into bipolarized and depolarized phases. We find two generic mechanisms governing the polarization dynamics and propose a coevolving framework that counts for opinion dynamics and network evolution simultaneously. Under a few generic assumptions on social interactions, we find a stable bipolarized community structure emerges naturally from the coevolving dynamics. Our theory analytically predicts two-phase transitions across three different polarization phases in line with the empirical observations for the Facebook and blogosphere data sets. Our theory not only accounts for the empirically observed scaling laws but also allows us to predict scaling exponents quantitatively.

Raman spectral classification algorithm of cephalosporin based on VGGNeXt.

In recent years, deep learning has been widely used in the field of Raman spectral classification. However, the majority of the training and test sets are generated by the same device (generally a portable Raman spectrometer), with little difference between them, and the trained model may not be directly applicable to other devices. In this study, we established a database of six cephalosporin Raman spectra and proposed a classification algorithm VGGNeXt for cephalosporin Raman spectra. VGGNeXt takes inspiration from ConvNeXt, borrows some tricks from Swin-T, and re-improves VGG. Training data were high-resolution spectra from a benchtop Raman spectrometer, and test data were low-resolution spectra from a portable Raman spectrometer. The impact of preprocessing and dataset size on algorithm accuracy was explored. The results show that our network outperforms other comparative algorithms in all cases. After preprocessing, the VGGNeXt model achieves 100% accuracy on both full and halved data sets, and 99.9% accuracy when there are only 10 data for each cephalosporin class. The results show that the experimental ideas and processing methods in this paper solve the problems of model transfer and instrument standardization to a certain extent, and the model has good robustness.

Enantioselective Total Synthesis of (-)-Arcutinine.

The first total synthesis of an arcutine-type C20-diterpenoid alkaloid arcutinine has been achieved in both racemic and asymmetric forms. Construction of the C4 quaternary center and the pyrrolidine E ring in an early stage proved to be important for achieving the successful synthesis of the target alkaloid. Strategically, an asymmetric conjugate addition/aldol cascade and a decarboxylative allylation reaction allowed the establishment of the vicinal all-carbon quaternary stereocenters at C4 and C5. Furthermore, a sequence consisting of an intramolecular aza-Wacker cyclization, an oxidative dearomatization/intramolecular Diels-Alder cycloaddition cascade, and a ketyl-olefin cyclization enabled the assembly of the core structure and led to the total synthesis of arcutinine.

A Desulfurative Strategy for the Generation of Alkyl Radicals Enabled by Visible-Light Photoredox Catalysis.

Herein, we present a new desulfurative method for generating primary, secondary, and tertiary alkyl radicals through visible-light photoredox catalysis. A process that involves the generation of N-centered radicals from sulfinamide intermediates, followed by subsequent fragmentation, is critical to forming the corresponding alkyl radical species. This strategy has been successfully applied to conjugate addition reactions that features mild reaction conditions, broad substrate scope (>60 examples), and good functional-group tolerance.

A novel method for quantitative determination of multiple substances using Raman spectroscopy combined with CWT.

The identification of mixed solutions is a challenging and important subject in chemical analysis. In this paper, we propose a novel workflow that enables rapid qualitative and quantitative detection of mixed solutions. We use a methanol-ethanol mixed solution as an example to demonstrate the superiority of this workflow. The workflow includes the following steps: (1) converting Raman spectra into Raman images through CWT; (2) using MobileNetV3 as the backbone network, improved multi-label and multi-channel synchronization enables simultaneous prediction of multiple mixture concentrations; and (3) using transfer learning and multi-stage training strategies for training to achieve accurate quantitative analysis. We compare six traditional machine learning algorithms and two deep learning models to evaluate the performance of our new method. The experimental results show that our model has achieved good prediction results when predicting the concentration of methanol and ethanol, and the coefficient of determination R2 is greater than 0.999. At different concentrations, both MAPE and RSD outperform other models, which demonstrates that our workflow has outstanding analytical capabilities. Importantly, we have solved the problem that current quantitative analysis algorithms for Raman spectroscopy are almost unable to accurately predict the concentration of multiple substances simultaneously. In conclusion, it is foreseeable that this non-destructive, automated, and highly accurate workflow can further advance Raman spectroscopy.

Bacteriophage protein Dap1 regulates evasion of antiphage immunity and Pseudomonas aeruginosa virulence impacting phage therapy in mice.

Bacteriophages have evolved diverse strategies to overcome host defence mechanisms and to redirect host metabolism to ensure successful propagation. Here we identify a phage protein named Dap1 from Pseudomonas aeruginosa phage PaoP5 that both modulates bacterial host behaviour and contributes to phage fitness. We show that expression of Dap1 in P. aeruginosa reduces bacterial motility and promotes biofilm formation through interference with DipA, a c-di-GMP phosphodiesterase, which causes an increase in c-di-GMP levels that trigger phenotypic changes. Results also show that deletion of dap1 in PaoP5 significantly reduces genome packaging. In this case, Dap1 directly binds to phage HNH endonuclease, prohibiting host Lon-mediated HNH degradation and promoting phage genome packaging. Moreover, PaoP5Δdap1 fails to rescue P. aeruginosa-infected mice, implying the significance of dap1 in phage therapy. Overall, these results highlight remarkable dual functionality in a phage protein, enabling the modulation of host behaviours and ensuring phage fitness.

StAP1 phage: an effective tool for treating methicillin-resistant Staphylococcus aureus infections.

Introduction: Staphylococcus aureus infection has long been a serious concern in the medical field, with methicillin-resistant Staphylococcus aureus (MRSA) posing a considerable challenge to public health. Given the escalating bacterial resistance and the favorable biosafety and environmental properties of phages, the resurgence of phage therapy offers a promising alternative to antibiotics. Methods: In this study, we isolated and characterized a MRSA phage named StAP1 from a Chinese hospital. Phenotypic and molecular analyses revealed its broad-spectrum characteristics, genomic background, and potential application in MRSA infection treatment. Results: Morphological examination classified the phage as a member of the Herelleviridae phage family, displaying a typical hexagonal head and a slender fibrous tail. Genomic analysis unveiled a size of ~144,705 bp for the StAP1 genome, encompassing 215 open reading frames (ORFs). The one-step growth curve demonstrated a 20-min incubation period for the phage, with an optimal multiplicity of infection (MOI) of 0.1. Moreover, StAP1 exhibited stability across a wide range of temperatures and pH levels. Further investigation of its broad-spectrum characteristics confirmed its ability to effectively infect all staphylococcal cassette chromosomal mec (SCCmec) types found in MRSA strains, notably displaying a remarkable lysis rate of 76.7% against the prevalent ST239 strain in China. In vivo studies show cased significant efficacy of the StAP1 phage against MRSA infection. Discussion: Overall, StAP1 phage presents a broad infection spectrum and exhibits strong lytic effects on various MRSA strains, highlighting its tremendous potential as a powerful tool for MRSA infection treatment.

Bacteriophage-Resistant Mutant of Enterococcus faecalis Is Impaired in Biofilm Formation.

Enterococcus faecalis is a common gram-positive non-spore-forming bacterium in nature and is found in the upper respiratory tract, intestine, and mouth of healthy people. E. faecalis is also one of the common pathogens causing nosocomial infections and is resistant to several antibiotics commonly used in practice. Thus, treating drug-resistant E. faecalis with antibiotics is challenging, and new approaches are needed. In this study, we isolated a bacteriophage named EFap02 that targets E. faecalis strain EFa02 from sewage at Southwest Hospital. Phage EFap02 belongs to the Siphoviridae family with a long tail of approximately 210 nm, and EFap02 can tolerate a strong acid and alkali environment and high temperature. Its receptor was identified as the capsular polysaccharide. Phage-resistant mutants had loss-of-function mutations in glycosyltransferase (gtr2), which is responsible for capsular polysaccharide biosynthesis, and this caused the loss of capsular polysaccharide and interruption of phage adsorption. Although phage-resistant mutants against EFap02 can be selected, such mutants are impaired in biofilm formation due to the loss of capsular polysaccharide, which compromises its virulence. Therefore, this study provided a detailed description of the E. faecalis EFap02 phage with the potential for treating E. faecalis infection.

Efficient wastewater treatment by membranes through constructing tunable antifouling membrane surfaces.

In the present study, a facile in situ approach for constructing tunable amphiphilic or hydrophilic antifouling membrane surfaces was demonstrated by exquisitely manipulating the microphase separation and surface segregation behavior of the tailor-made ternary amphiphilic block copolymers during the commonly utilized wet phase inversion membrane-formation process. Under dead-end filtration for oily wastewater treatment, the membrane with amphiphilic surface exhibited over 99.5% retention ratio of chemical oxygen demand (COD) without appreciable membrane fouling: the water permeation flux was slightly decreased during operation (total flux decline was 6.8%) and almost completely recovered to the initial value (flux recovery ratio was more than 99.0%) after simple hydraulic washing. While for the proteins-containing wastewater treatment, the membrane with hydrophilic surface exhibited about 52.6% COD retention ratio and superior antifouling performance: only 17.0% total flux decline and also more than 99.0% flux recovery ratio. Hopefully, the present approach can be developed as a competitive platform technology for the preparation of robust and versatile antifouling membrane, leading to the high process efficiency of wastewater treatments.

Association Between System Usage Pattern and Impact of Web-Based Telerehabilitation in Patients with Multiple Sclerosis.

Patients with multiple sclerosis (PwMS) increasingly use online services for managing their healthcare. The objective of this study was to investigate web log data (weblogs) generated by PwMS in the process of web-based telerehabilitation and correlate them with rehabilitation progress. The weblogs from 17 patients (female: 15, male 2; mean age: 60.1±11.4 years) were tracked for an average period of 153.6±38.3 days with the total number of log events and page visit records of 1,457 and 37,030, respectively. The time and frequency of patients' web visits were investigated as well as their adherence to prescribed exercise regimen. Rehabilitation progress was gauged by changes in quality of life, mobility, and sleep ascertained by measuring MSQOL, 2MWT and PSQI respectively. The changes in these metrics were correlated with system usage patterns. On average, PwMS visited 30 pages a day for 26.5 minutes, with a single login amounting for 27 pages in duration of 22.0 minutes. The average exercise program comprised 6.9 sets and 29.1 repetitions with average set and repetition completion rates of 46.5% and 72.6% respectively. A statistically significant association has been found between time spent in the online exercise mode and clinical improvements. The results of the study demonstrate that the patients had more pronounced outcome improvements when they increased the time of using the telerehabilitation system for home-based exercise. The results of this study could contribute to the development of more efficient home-based telerehabilitation systems.

Towards a Highly Usable, Mobile Electronic Platform for Patient Recruitment and Consent Management.

This study seeks to assess usability and acceptance of E-Consent on mobile devices such as tablet computers for collecting universal biobank consents. Usability inspection occurred via cognitive walkthroughs and heuristics evaluations, supplemented by surveys to capture health literacy, patient engagement, and other metrics. 17 patients of varied ages, backgrounds, and occupations participated in the study. The System Usability Scale (SUS) provided a standardized reference for usability and satisfaction, and the mean result of 84.4 placed this mobile iteration in the top 10th percentile. A semi-structured qualitative interview provided copious actionable feedback, which will inform the next iteration of this project. Overall, this implementation of the E-Consent framework on mobile devices was considered easy-to-use, satisfying, and engaging, allowing users to progress through the consent materials at their own pace. The platform has once again demonstrated high usability and high levels of user acceptance, this time in a novel setting.

Economic burden of readmission due to postoperative cerebrospinal fluid leak in Chinese patients.

Aim: This real-world data study investigated the economic burden and associated factors of readmissions for cerebrospinal fluid leakage (CSFL) post-cranial, transsphenoidal, or spinal index surgeries. Methods: Costs of CSFL readmissions and index hospitalizations during 2014-2018 were collected. Readmission cost was measured as absolute cost and as percentage of index hospitalization cost. Factors associated with readmission cost were explored using generalized linear models. Results: Readmission cost averaged US$2407-6106, 35-94% of index hospitalization cost. Pharmacy costs were the leading contributor. Generalized linear models showed transsphenoidal index surgery and surgical treatment for CSFL were associated with higher readmission costs. Conclusion: CSFL readmissions are a significant economic burden in China. Factors associated with higher readmission cost should be monitored.

Safety and efficacy of tracheotomy for critically ill patients with coronavirus disease 2019 (COVID-19) in Wuhan: a case series of 14 patients.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is a global pandemic. Critically ill patients often require prolonged intubation for mechanical ventilation to support breathing; thus, the artificial airway must be managed by tracheotomy. Therefore, studies exploring appropriate and safe methods for tracheotomy that minimize the risks of nosocomial transmission are important. METHODS: A retrospective analysis of the clinical characteristics of 14 critically ill patients with COVID-19, who underwent bedside tracheotomy from March to April 2020 was conducted to summarize the indications for tracheotomy and key points related to personal protective equipment and surgical procedures. RESULTS: All 14 patients were diagnosed with COVID-19 and were critically ill. All tracheotomies were performed in the late phase of the infection course. The interval between the infection and tracheotomy was 33 days, and the median interval between intubation and tracheotomy was 25.5 days. The reverse transcription-polymerase chain reaction results of secretions from the operative incision and inside the tracheotomy tube were negative. Twelve patients improved after tracheotomy, with SpO2 levels maintained above 96%. One patient died of progressive respiratory failure; another patient died of uncontrolled septic shock. No medical staff who participated in the tracheotomy was infected. CONCLUSIONS: Tracheotomy in critically ill patients with COVID-19 who meet the indications for tracheotomy potentially represents a safer approach to manage the airway and help improve the treatment outcomes. A tracheotomy performed in the late phase of the disease has a relatively low risk of infection. Adherence to key steps in the tracheotomy procedure and donning adequate personal protection will help medical staff avoid infection.

Influence of intermittent water releases on groundwater chemistry at the lower reaches of the Tarim River, China.

Based on the data of the depths and the chemical properties of groundwater, salinity in the soil profile, and the basic information on each delivery of water collected from the years 2000 to 2006, the varied character of groundwater chemistry and related factors were studied. The results confirmed the three stages of the variations in groundwater chemistry influenced by the intermittent water deliveries. The factors that had close relations to the variations in groundwater chemistry were the distances of monitoring wells from the water channel, the depths of the groundwater, water flux in watercourse, and the salinities in soils. The relations between chemical variation and groundwater depths indicated that the water quality was the best with the groundwater varying from 5 to 6 m. In addition, the constructive species in the study area can survive well with the depth of groundwater varying from 5 to 6 m, so the rational depth of groundwater in the lower reaches of the Tarim River should be 5 m or so. The redistribution of salts in the soil profile and its relations to the chemical properties and depths of groundwater revealed the linear water delivery at present combining with surface water supply in proper sections would promote water quality optimized and speed up the pace of ecological restoration in the study area.

Usability Inspection of Multipurpose Scalable Informed Consent Platform.

We developed a multipurpose scalable electronic informed consent platform (E-Consent) which is reusable for any informed consent in a multitude of settings. The platform allows research staff to easily upload multimedia information about a research protocol with an approved informed consent into the system, which delivers this content interactively for prospective study candidates in a user-friendly way. Consistent with user-centered design, E-Consent underwent usability inspection via cognitive walkthroughs accompanied by surveys that captured task complexity on a 5-point Likert-type scale. The System Usability Scale (SUS) provided a standardized reference for usability and satisfaction. Overall, the E-Consent framework was considered by participants to be easy-to-use, satisfying, and timely, while delivering complex information such as that on a consent form. E-Consent ranked in the top 10th percentile for usability as measured by SUS. This extensible framework successfully delivered complex information and recorded user consents, all in an easy-to-understand and highly usable fashion.

Factors Affecting Adherence with Telerehabilitation in Patients with Multiple Sclerosis.

The goal of this study was to identify predictors of telerehabilitation adherence in patients with multiple sclerosis (MS). An adherence prediction model was based on baseline patient characteristics. Such a model may be useful for identifying patients who require higher levels of engagements in the early stages of home telerehabilitation programs. The resulting set of predictive features included education, patient satisfaction with the program, and psychological domain of the MS Impact Scale. Resulting prediction of high and low adherence had overall 80.0% accuracy, 81.8% sensitivity, and 77.8% specificity. We concluded that the baseline patient information may be instrumental in personalizing levels of support and training necessary for active patient participation in telerehabilitation.

Cross-sectional survey on job satisfaction and its associated factors among doctors in tertiary public hospitals in Shanghai, China.

OBJECTIVES: Doctors in public hospitals in China face considerable pressure and excessive workloads, which are likely to predispose them to job dissatisfaction. We explored the job satisfaction of doctors and examined the influence of diverse sociodemographic characteristics. DESIGN: This was a cross-sectional study. SETTING: Eleven tertiary public hospitals in Shanghai, China. PARTICIPANTS: The questionnaire was designed based on the fifth National Health Service General Research, which was based on the Minnesota Satisfaction Questionnaire. Questionnaires were administered to 897 doctors randomly (using random number tables) and 730 were returned completed (response rate=81.4%). Doctors who volunteered and provided informed, written consent participated. PRIMARY OUTCOME MEASURES: The dependent variable was doctors' job satisfaction. RESULTS: Statistical analyses were conducted using SPSS and SAS. Overall, 64.8% of participants were dissatisfied with their jobs. Factors that were statistically significant to doctors' job satisfaction in the univariate analysis were entered into the logistic regression analysis, including doctors' professional title, department, work hours, work requirements (reflected as the number of patients they diagnosed and treated monthly), life and work stress, and the types of patients that doctors treated or expected to treat. The results of the logistic regression analysis suggested that doctors' job satisfaction was related to their professional title, types of patients that doctors treated or expected to treat, as well as their work stress. CONCLUSIONS: There is an urgent need for public hospitals in China to establish a more reasonable promotion and management system for doctors, encourage patients to accept the two-way referral, pay more attention to less-experienced staff and help doctors release their work stress.

Designing Telerehabilitation System for Multipronged Exercise in Patients with Multiple Sclerosis.

Patients with multiple sclerosis (PwMS) were shown to greatly benefit from multipronged exercise interventions comprising aerobic, resistance and corrective therapeutic components which result in endurance and strength improvement and reduction of fatigue and spasticity. However, telerehabilitation support of multipronged exercise programs in PwMS with significant mobility impairment has received limited attention. It is not clear whether severely disabled PwMS can successfully operate a telerehabilitation system at home independently. The goal of this study was to design a telerehabilitation system for individualized multipronged exercise programs and to assess the feasibility of the initial prototype in PwMS with significant mobility impairment. Usability assessment was based on the evaluation of patient ability to successfully carry out a standardized list of common tasks necessary to operate the system. For each task, time to completion, perceived difficulty and satisfaction were documented. Our results indicated a high level of acceptance of the system by these patients. On average, it took 83±41 seconds to complete all the major tasks necessary to operate the telerehabilitation system. After the initial introduction, all patients were able to successfully use the system and follow their individualized exercise prescription independently. A definitive systematic evaluation in a randomized clinical trial is warranted to demonstrate potential clinical impact of telerehabilitation in PwMS.