Monitoring Activity and Gait in Children (MAGIC) using digital health technologies.

BACKGROUND: Digital health technologies (DHTs) can collect gait and physical activity in adults, but limited studies have validated these in children. This study compared gait and physical activity metrics collected using DHTs to those collected by reference comparators during in-clinic sessions, to collect a normative accelerometry dataset, and to evaluate participants' comfort and their compliance in wearing the DHTs at-home. METHODS: The MAGIC (Monitoring Activity and Gait in Children) study was an analytical validation study which enrolled 40, generally healthy participants aged 3-17 years. Gait and physical activity were collected using DHTs in a clinical setting and continuously at-home. RESULTS: Overall good to excellent agreement was observed between gait metrics extracted with a gait algorithm from a lumbar-worn DHT compared to ground truth reference systems. Majority of participants either "agreed" or "strongly agreed" that wrist and lumbar DHTs were comfortable to wear at home, respectively, with 86% (wrist-worn DHT) and 68% (lumbar-worn DHT) wear-time compliance. Significant differences across age groups were observed in multiple gait and activity metrics obtained at home. CONCLUSIONS: Our findings suggest that gait and physical activity data can be collected from DHTs in pediatric populations with high reliability and wear compliance, in-clinic and in home environments. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04823650 IMPACT: Digital health technologies (DHTs) have been used to collect gait and physical activity in adult populations, but limited studies have validated these metrics in children. The MAGIC study comprehensively validates the performance and feasibility of DHT-measured gait and physical activity in the pediatric population. Our findings suggest that reliable gait and physical activity data can be collected from DHTs in pediatric populations, with both high accuracy and wear compliance both in-clinic and in home environments. The identified across-age-group differences in gait and activity measurements highlighted their potential clinical value.

Towards understanding the lower CH4 selectivity of HCP-Co than FCC-Co in Fischer-Tropsch synthesis.

In Fischer-Tropsch synthesis (FTS), the cobalt catalyst has higher C5+ and lower CH4 selectivity in the hcp phase than in the fcc phase. However, a detailed explanation of the intrinsic mechanism is still missing. The underlying reason was explored combining density functional theory, Wulff construction, and a particle-level descriptor based on the slab model of surfaces that are prevalent in the Wulff shape to provide single-particle level understanding. Using a particle-level indicator of the reaction rates, we have shown that it is more difficult to form CH4 on hcp-Co than on fcc-Co, due to the larger effective barrier difference of CH4 formation and C-C coupling on hcp-Co particles, which leads to the lower CH4 selectivity of hcp-Co in FTS. Among the exposed facets of fcc-Co, the (311) surface plays a pivotal role in promoting CH4 formation. The reduction of CH4 selectivity in cobalt-based FTS is achievable through phase engineering of Co from fcc to hcp or by tuning the temperature and size of the particles.

The diagnostic performance of V' and U' variables as an objective index of pink-color sign for diagnosing esophageal cancerous lesions.

BACKGROUND: The pink-color sign (PCS) has been widely used for diagnosing esophageal squamous cell carcinoma (ESCC) during Lugol's iodine chromoendoscopy. However, the identification of the PCS only relies on the subjective assessments made by the endoscopist, which could lead to bias and disagreement. Previous research has indicated that the V' variable can, as an objective index, define the PCS in the LU'V' color space. We aimed to validate the diagnostic performance of the PCS defined by the V' variable alone and attempt to improve the diagnostic performance by combining the V' and U' variables. METHODS: We re-examined 231 subjects with Lugol's unstained lesions (LULs) from a previously reported prospective trial. The diagnostic performance of the method using V' variable alone (V' alone method), the combination method using V' and U' variables (V' + U' method), and the endoscopists were calculated and compared. RESULTS: A total of 236 LULs were included, among which 46 were histologically confirmed to be cancerous lesions. The sensitivity, specificity, and accuracy of the V' alone method were 73.91% (95% CI 58.87-85.73%), 79.47% (95% CI 73.03-84.98%), and 78.39% (95% CI 72.59-83.47%) in the external validation cohort, respectively. It is inferior to endoscopists in terms of specificity and accuracy. The V' + U' method demonstrated a diagnostic performance comparable to the experienced endoscopists, with sensitivity, specificity, and accuracy of 76.74% (95% CI 61.37-88.25%), 88.64% (95% CI 83.00-92.92%), and 86.30% (95% CI 81.03-90.56%), respectively. CONCLUSION: The V' alone method exhibited lower specificity and accuracy than the experienced endoscopist and the V' + U' method. However, the modified V' + U' method demonstrated a diagnostic performance comparable to experienced endoscopists. Utilizing the objective index of the PCS could provide valuable support in clinical decision-making.

Function analysis of choline binding domains (CBDs) of LytA, LytC and CbpD in biofilm formation of Streptococcus pneumoniae.

Biofilm formation is an important strategy for the colonization of Streptococcus pneumoniae, which can increase the capacity to evade antibiotic and host immune stress. Extracellular choline-binding proteins (CBPs) are required for successful biofilm formation, but the function of extracellular CBPs in the process of biofilm formation is not fully understood. In this study, we tend to analyze the functions of LytA, LytC and CbpD in biofilm formation by in vitro studies with their choline-binding domains (CBDs). Biofilm formation of S. pneumoniae was enhanced when cultured in medium supplemented with CBD-C and CBD-D. Parallel assays with ChBp-Is (choline binding repeats with different C-terminal tails) and character analysis of CBDs reveal a higher isoelectric point (pI) is related to promotion of biofilm formation. Phenotype characterization of biofilms revel CBD-C and CBD-D function differently, CBD-C promoting the formation of membrane-like structures and CBD-D promoting the formation of regular reticular structures. Gene expression analysis reveals membrane transport pathways are influenced with the binding of CBDs, among which the phosphate uptake and PTS of galactose pathways are both up-regulated under conditions with CBDs. Further, extracellular substances detection revealed that extracellular proteins increased with CBD-A and CBD-D, exhibiting as increase in extracellular high molecular weight proteins. Extracellular DNA increased under CBD-A but decreased under CBD-C and CBD-D; Extracellular phosphate increased under CBD-C. These support the alterations in membrane transport pathways, and reveal diverse reactions to extracellular protein, DNA and phosphate of these three CBDs. Overall, our results indicated extracellular CBP participate in biofilm formation by affecting surface charge and membrane transport pathways of pneumococcal cells, as well as promoting reactions to extracellular substances.

Fetal heart rate responses to maternal sleep-disordered breathing.

BACKGROUND: Maternal sleep-disordered breathing is associated with adverse pregnancy outcomes and is considered to be deleterious to the developing fetus. Maternal obesity potentiates sleep-disordered breathing, which, in turn, may contribute to the effect of maternal obesity on adverse fetal outcomes. However, only a few empirical studies have evaluated the contemporaneous effects of maternal sleep-disordered breathing events on fetal well-being. These events include apnea and hypopnea with accompanying desaturations in oxyhemoglobin. OBJECTIVE: This study aimed to reconcile contradictory findings on the associations between maternal apnea or hypopnea events and clinical indicators of fetal compromise. It also sought to broaden the knowledge base by examining the fetal heart rate and heart rate variability before, during, and after episodes of maternal apnea or hypopnea. To accomplish this, we employed overnight polysomnography, the gold standard for ascertaining maternal sleep-disordered breathing, and synchronized it with continuous fetal electrocardiography. STUDY DESIGN: A total of 84 pregnant women with obesity (body mass index >30 kg/m2) participated in laboratory-based polysomnography with digitized fetal electrocardiography recordings during or near 36 weeks of gestation. Sleep was recorded, on average, for 7 hours. Decelerations in fetal heart rate were identified. Fetal heart rate and heart rate variability were quantified before, during, and after each apnea or hypopnea event. Event-level intensity (desaturation magnitude, duration, and nadir O2 saturation level) and person-level characteristics based on the full overnight recording (apnea-hypopnea index, mean O2 saturation, and O2 saturation variability) were analyzed as potential moderators using linear mixed effects models. RESULTS: A total of 2936 sleep-disordered breathing events were identified, distributed among all but 2 participants. On average, participants exhibited 8.7 episodes of apnea or hypopnea per hour (mean desaturation duration, 19.1 seconds; mean O2 saturation nadir, 86.6% per episode); nearly half (n=39) of the participants met the criteria for obstructive sleep apnea. Only 45 of 2936 apnea or hypopnea events were followed by decelerations (1.5%). Conversely, most (n=333, 88%) of the 378 observed decelerations, including the prolonged ones, did not follow an apnea or a hypopnea event. Maternal sleep-disordered breathing burden, body mass index, and fetal sex were unrelated to the number of decelerations. Fetal heart rate variability increased during events of maternal apnea or hypopnea but returned to initial levels soon thereafter. There was a dose-response association between the size of the increase in fetal heart rate variability and the maternal apnea-hypopnea index, event duration, and desaturation depth. Longer desaturations were associated with a decreased likelihood of the variability returning to baseline levels after the event. The mean fetal heart rate did not change during episodes of maternal apnea or hypopnea. CONCLUSION: Episodes of maternal sleep apnea and hypopnea did not evoke decelerations in the fetal heart rate despite the predisposing risk factors that accompany maternal obesity. The significance of the modest transitory increase in fetal heart rate variability in response to apnea and hypopnea episodes is not clear but may reflect compensatory, delimited autonomic responses to momentarily adverse conditions. This study found no evidence that episodes of maternal sleep-disordered breathing pose an immediate threat, as reflected in fetal heart rate responses, to the near-term fetus.

An Efficient Way to Model Complex Iron Carbides: A Benchmark Study of DFTB2 against DFT.

Iron carbides have attracted increasing attention in recent years due to their enormous potential in catalytic fields, such as Fischer-Tropsch synthesis and the growth of carbon nanotubes. Theoretical calculations can provide a more thorough understanding of these reactions at the atomic scale. However, due to the extreme complexity of the active phases and surface structures of iron carbides at the operando conditions, calculations based on density functional theory (DFT) are too costly for realistically large models of iron carbide particles. Therefore, a cheap and efficient quantum mechanical simulation method with accuracy comparable to DFT is desired. In this work, we adopt the spin-polarized self-consistent charge density functional tight-binding (DFTB2) method for iron carbides by reparametrization of the repulsive part of the Fe-C interactions. To assess the performance of the improved parameters, the structural and electronic properties of iron carbide bulks and clusters obtained with DFTB2 method are compared with the previous experimental values and the results obtained with DFT approach. Calculated lattice parameters and density of states are close to DFT predictions. The benchmark results show that the proposed parametrization of Fe-C interactions provides transferable and balanced description of iron carbide systems. Therefore, spin-polarized DFTB2 is valued as an efficient and reliable method for the description of iron carbide systems.

Computer-aided diagnosis in predicting the invasion depth of early colorectal cancer: a systematic review and meta-analysis of diagnostic test accuracy.

BACKGROUND: Endoscopic resection (ER) is widely applied to treat early colorectal cancer (CRC). Predicting the invasion depth of early CRC is critical in determining treatment strategies. The use of computer-aided diagnosis (CAD) algorithms could theoretically make accurate and objective predictions regarding the suitability of lesions for ER indication based on invasion depth. This study aimed to assess diagnostic test accuracy of CAD algorithms in predicting the invasion depth of early CRC and to compare the performance between the CAD algorithms and endoscopists. METHODS: Multiple databases were searched until June 30, 2022 for studies that evaluated the diagnostic performance of CAD algorithms for invasion depth of CRC. Meta-analysis of diagnostic test accuracy using a bivariate mixed-effects model was performed. RESULTS: Ten studies consisting of 13 arms (13,918 images from 1472 lesions) were included. Due to significant heterogeneity, studies were stratified into Japan/Korea-based or China-based studies. For the former, the area under the curve (AUC), sensitivity, and specificity of the CAD algorithms were 0.89 (95% CI 0.86-0.91), 62% (95% CI 50-72%), and 96% (95% CI 93-98%), respectively. For the latter, AUC, sensitivity, and specificity were 0.94 (95% CI 0.92-0.96), 88% (95% CI 78-94%), and 88% (95% CI 80-93%), respectively. The performance of the CAD algorithms in Japan/Korea-based studies was not significantly different from that of all endoscopists (0.88 vs. 0.91, P = 0.10) but was inferior to that of expert endoscopists (0.88 vs. 0.92, P = 0.03). The performance of the CAD algorithms in China-based studies was better than that of all endoscopists (0.94 vs. 0.90, P = 0.01). CONCLUSION: The CAD algorithms showed comparable accuracy for prediction of invasion depth of early CRC compared to all endoscopists, which was still lower than expert endoscopists in diagnostic accuracy; more improvements should be achieved before it can be extensively applied to clinical practice.

Dynamic changes of gut bacterial communities present in larvae of Anoplophora glabripennies collected at different developmental stages.

The Asian long-horned beetle, Anoplophora glabripennies (Motschulsky), is a destructive wood-boring pest that is capable of killing healthy trees. Gut bacteria in the larvae of the wood-boring pest is essential for the fitness of hosts. However, little is known about the structure of the intestinal microbiome of A. glabripennies during larval development. Here, we used Illumina MiSeq high-throughput sequencing technology to analyze the larval intestinal bacterial communities of A. glabripennies at the stages of newly hatched larvae, 1st instar larvae and 4th instar larvae. Significant differences were found in larval gut microbial community structure at different larvae developmental stages. Different dominant genus was detected during larval development. Acinetobacter were dominant in the newly hatched larvae, Enterobacter and Raoultella in the 1st instar larvae, and Enterococcus and Gibbsiella in the 4th instar larvae. The microbial richness in the newly hatched larvae was higher than those in the 1st and 4th instar larvae. Many important functions of the intestinal microbiome were predicted, for example, fermentation and chemoheterotrophy functions that may play an important role in insect growth and development was detected in the bacteria at all tested stages. However, some specific functions are found to be associated with different development stages. Our study provides a theoretical basis for investigating the function of the intestinal symbiosis bacteria of A. glabripennies.

Hypertonic solution as an optimal submucosal injection solution for endoscopic resection of gastrointestinal mucosal lesions: Systematic review and network meta-analysis.

OBJECTIVES: Based on different physicochemical properties, common submucosal injection solutions could be classified into three categories: normal saline solution (NS), hypertonic solution (HS), and viscous solution (VS). We compared the efficacy and safety of various categories of solutions in this network meta-analysis of randomized controlled trials (RCTs) to identify the optimal submucosal injection fluid. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for RCTs that compared the efficacy and safety of NS, HS, and VS during endoscopic resection for gastrointestinal (GI) mucosal lesions. Pairwise and network analyses were conducted to determine the ranking of different fluids. RESULTS: Thirteen RCTs were included in the final analysis with 1637 patients (1639 lesions). HS outperformed NS in rates of en bloc (pooled relative risk [RR] 1.50; 95% confidence interval [CI] 1.10-1.90), overall bleeding (pooled odds ratio [OR] 0.33; 95% CI 0.10-0.88; lesions >10 mm OR 4.65 × 10-2 ; 95% CI 1.10 × 10-3 -0.46), and intraoperative bleeding (lesions >10 mm OR 7.10 × 10-6 ; 95% CI 4.30 × 10-18 -0.26). HS showed the highest probability of ranking first in each outcome except for the volume of injection. Although VS was superior to NS in rates of en bloc, overall, and intraoperative bleeding in the lesions >10 mm subgroup, and required less fluid in pooled analysis, it ranked last in cost of submucosal injection solution. CONCLUSIONS: Both HS and VS were superior to NS in comparisons of efficacy and safety. Considering the better performance and potentially low cost, HS might be an optimal choice during gastrointestinal endoscopic resection, especially for colorectal endoscopic mucosal resection.

Similar gut bacteria composition in Apriona germari on two preferred host plants.

Apriona germari is one of the most serious wood-boring pests that cause damage to economic and landscaping trees and has adapted to a wide range of plants as diet. Gut bacteria play an important role in biology and ecology of herbivores, especially in growth and adaptation. To investigate how plant hosts shape A. germari gut microbiota, A. germari larvae were collected from Populus tomentosa and Malus pumilal, and gut microbiomes were sequenced based on 16S rDNA high-throughput sequencing technology. A total of 853,424 high-quality reads were obtained and clustered into 196 operational taxonomic units under a 97% similarity cutoff, which were annotated into 8 phyla, 10 classes, 21 orders, 34 families, 59 genera, and 39 species. Gibbsiella was the most dominant genus of intestinal bacteria, followed by Enterobacter and Acinetobacter. No significant difference was observed in larvae gut bacterial richness and diversity of A. germari collected from two hosts, though alpha diversity showed that the richness of gut bacteria in A. germari larvae collected on P. tomentosa was slightly higher than that in A. germari on M. pumilal, and beta diversity showed little difference between two host plants. The functional abundance analysis of the detected bacteria revealed fermentation, chemoheterotrophy, symbionts, and nitrate relative functions that highly possibly support wood-boring beetles to feed on woody tissues. Our study provided a theoretical basis for investigating the function of intestinal symbiosis bacteria of A. germari.

Carbapenem-resistant K. pneumoniae exhibiting clinically undetected amikacin and meropenem heteroresistance leads to treatment failure in a murine model of infection.

Heteroresistance is a poorly understood mechanism of resistance which refers to a phenomenon where there are different subpopulations of seemingly isogenic bacteria which exhibit a range of susceptibilities to a particular antibiotic. In the current study, we identified a multidrug-resistant, carbapenemase-positive K. pneumoniae strain SWMUF35 which was classified as susceptible to amikacin and resistant to meropenem by clinical diagnostics yet harbored different subpopulations of phenotypically resistant cells, and has the ability to form biofilm. Population analysis profile (PAP) indicated that SWMUF35 showed heteroresistance towards amikacin and meropenem which was considered as co-heteroresistant K. pneumoniae strain. In vitro experiments such as dual PAP, dual Times-killing assays and checkerboard assay showed that antibiotic combination therapy (amikacin combined with meropenem) can effectively combat SWMUF35. Importantly, using an in vivo mouse model of peritonitis, we found that amikacin or meropenem monotherapy was unable to rescue mice infected with SWMUF35. Antibiotic combination therapy could be a rational strategy to use clinically approved antibiotics when monotherapy would fail. Furthermore, our data warn that antibiotic susceptibility testing results may be unreliable due to undetected heteroresistance which can lead to treatment failure and the detection of this phenotype is a prerequisite for a proper choice of antibiotic to support a successful treatment outcome.

Fetal heart rate during maternal sleep.

Despite prolonged and cumulative exposure during gestation, little is known about the fetal response to maternal sleep. Eighty-four pregnant women with obesity (based on pre-pregnancy BMI) participated in laboratory-based polysomnography (PSG) with continuous fetal electrocardiogram monitoring at 36 weeks gestation. Multilevel modeling revealed both correspondence and lack of it in maternal and fetal heart rate patterns. Fetal heart rate (fHR) and variability (fHRV), and maternal heart rate (mHR) and variability (mHRV), all declined during the night, with steeper rates of decline prior to 01:00. fHR declined upon maternal sleep onset but was not otherwise associated with maternal sleep stage; fHRV differed during maternal REM and NREM. There was frequent maternal waking after sleep onset (WASO) and fHRV and mHRV were elevated during these episodes. Cross-correlation analyses revealed little temporal coupling between maternal and fetal heart rate, except during WASO, suggesting that any observed associations in maternal and fetal heart rates during sleep are the result of other physiological processes. Implications of the maternal sleep context for the developing fetus are discussed, including the potential consequences of the typical sleep fragmentation that accompanies pregnancy.

Data mining-based model and risk prediction of colorectal cancer by using secondary health data: A systematic review.

OBJECTIVE: Prevention and early detection of colorectal cancer (CRC) can increase the chances of successful treatment and reduce burden. Various data mining technologies have been utilized to strengthen the early detection of CRC in primary care. Evidence synthesis on the model's effectiveness is scant. This systematic review synthesizes studies that examine the effect of data mining on improving risk prediction of CRC. METHODS: The PRISMA framework guided the conduct of this study. We obtained papers via PubMed, Cochrane Library, EMBASE and Google Scholar. Quality appraisal was performed using Downs and Black's quality checklist. To evaluate the performance of included models, the values of specificity and sensitivity were comparted, the values of area under the curve (AUC) were plotted, and the median of overall AUC of included studies was computed. RESULTS: A total of 316 studies were reviewed for full text. Seven articles were included. Included studies implement techniques including artificial neural networks, Bayesian networks and decision trees. Six articles reported the overall model accuracy. Overall, the median AUC is 0.8243 [interquartile range (IQR): 0.8050-0.8886]. In the two articles that reported comparison results with traditional models, the data mining method performed better than the traditional models, with the best AUC improvement of 10.7%. CONCLUSIONS: The adoption of data mining technologies for CRC detection is at an early stage. Limited numbers of included articles and heterogeneity of those studies implied that more rigorous research is expected to further investigate the techniques' effects.

A two-stage model for wearable device data.

Recent advances of wearable computing technology have allowed continuous health monitoring in large observational studies and clinical trials. Examples of data collected by wearable devices include minute-by-minute physical activity proxies measured by accelerometers or heart rate. The analysis of data generated by wearable devices has so far been quite limited to crude summaries, for example, the mean activity count over the day. To better utilize the full data and account for the dynamics of activity level in the time domain, we introduce a two-stage regression model for the minute-by-minute physical activity proxy data. The model allows for both time-varying parameters and time-invariant parameters, which helps capture both the transition dynamics between active/inactive periods (Stage 1) and the activity intensity dynamics during active periods (Stage 2). The approach extends methods developed for zero-inflated Poisson data to account for the high-dimensionality and time-dependence of the high density data generated by wearable devices. Methods are motivated by and applied to the Baltimore Longitudinal Study of Aging.

A practical guide to big data.

Big Data is increasingly prevalent in science and data analysis. We provide a short tutorial for adapting to these changes and making the necessary adjustments to the academic culture to keep Biostatistics truly impactful in scientific research.

Normalization and extraction of interpretable metrics from raw accelerometry data.

We introduce an explicit set of metrics for human activity based on high-density acceleration recordings from a hip-worn tri-axial accelerometer. These metrics are based on two concepts: (i) Time Active, a measure of the length of time when activity is distinguishable from rest and (ii) AI, a measure of the relative amplitude of activity relative to rest. All measurements are normalized (have the same interpretation across subjects and days), easy to explain and implement, and reproducible across platforms and software implementations. Metrics were validated by visual inspection of results and quantitative in-lab replication studies, and by an association study with health outcomes.

Transmembrane serine protease 6, a novel target for inhibition of neuronal tumor growth.

Transmembrane serine protease 6 (Tmprss6) has been correlated with the occurrence and progression of tumors, but any specific molecular mechanism linking the enzyme to oncogenesis has remained elusive thus far. In the present study, we found that Tmprss6 markedly inhibited mouse neuroblastoma N2a (neuro-2a) cell proliferation and tumor growth in nude mice. Tmprss6 inhibits Smad1/5/8 phosphorylation by cleaving the bone morphogenetic protein (BMP) co-receptor, hemojuvelin (HJV). Ordinarily, phosphorylated Smad1/5/8 binds to Smad4 for nuclear translocation, which stimulates the expression of hepcidin, ultimately decreasing the export of iron through ferroportin 1 (FPN1). The decrease in cellular iron levels in neuro-2a cells with elevated Tmprss6 expression limited the availability of the metal forribo nucleotide reductase activity, thereby arresting the cell cycle prior to S phase. Interestingly, Smad4 promoted nuclear translocation of activating transcription factor 3 (ATF3) to activate the p38 mitogen-activated protein kinases signaling pathway by binding to ATF3, inducing apoptosis of neuro-2a cells and inhibiting tumor growth. Disruption of ATF3 expression significantly decreased apoptosis in Tmprss6 overexpressed neuro-2a cells. Our study describes a mechanism whereby Tmprss6 regulates the cell cycle and apoptosis. Thus, we propose Tmprss6 as a candidate target for inhibiting neuronal tumor growth.

Stabilized ε-Fe2C catalyst with Mn tuning to suppress C1 byproduct selectivity for high-temperature olefin synthesis.

Accurately controlling the product selectivity in syngas conversion, especially increasing the olefin selectivity while minimizing C1 byproducts, remains a significant challenge. Epsilon Fe2C is deemed a promising candidate catalyst due to its inherently low CO2 selectivity, but its use is hindered by its poor high-temperature stability. Herein, we report the successful synthesis of highly stable ε-Fe2C through a N-induced strategy utilizing pyrolysis of Prussian blue analogs (PBAs). This catalyst, with precisely controlled Mn promoter, not only achieved an olefin selectivity of up to 70.2% but also minimized the selectivity of C1 byproducts to 19.0%, including 11.9% CO2 and 7.1% CH4. The superior performance of our ε-Fe2C-xMn catalysts, particularly in minimizing CO2 formation, is largely attributed to the interface of dispersed MnO cluster and ε-Fe2C, which crucially limits CO to CO2 conversion. Here, we enhance the carbon efficiency and economic viability of the olefin production process while maintaining high catalytic activity.

Bacteriophage-resistant carbapenem-resistant Klebsiella pneumoniae shows reduced antibiotic resistance and virulence.

Phage therapy has shown great promise in the treatment of bacterial infections. However, the effectiveness of phage therapy is compromised by the inevitable emergence of phage-resistant strains. In this study, a phage-resistant carbapenem-resistant Klebsiella pneumoniae strain SWKP1711R, derived from parental carbapenem-resistant K. pneumoniae strain SWKP1711 was identified. The mechanism of bacteriophage resistance in SWKP1711R was investigated and the molecular determinants causing altered growth characteristics, antibiotic resistance, and virulence of SWKP1711R were tested. Compared to SWKP1711, SWKP1711R showed slower growth, smaller colonies, filamentous cells visible under the microscope, reduced production of capsular polysaccharide (CPS) and lipopolysaccharide, and reduced resistance to various antibiotics accompanied by reduced virulence. Adsorption experiments showed that phage vB_kpnM_17-11 lost the ability to adsorb onto SWKP1711R, and the adsorption receptor was identified to be bacterial surface polysaccharides. Genetic variation analysis revealed that, compared to the parental strain, SWKP1711R had only one thymine deletion at position 78 of the open reading frame of the lpcA gene, resulting in a frameshift mutation that caused alteration of the bacterial surface polysaccharide and inhibition of phage adsorption, ultimately leading to phage resistance. Transcriptome analysis and quantitative reverse transcriptase PCR revealed that genes encoding lipopolysaccharide synthesis, ompK35, blaTEM-1, and type II and Hha-TomB toxin-antitoxin systems, were all downregulated in SWKP1711R. Taken together, the evidence presented here indicates that the phenotypic alterations and phage resistance displayed by the mutant may be related to the frameshift mutation of lpcA and altered gene expression. While evolution of phage resistance remains an issue, our study suggests that the reduced antibiotic resistance and virulence of phage-resistant strain derivatives might be beneficial in alleviating the burden caused by multidrug-resistant bacteria.