Assessing the quality and eco-beneficial microbes in the use of silkworm excrement compost.

Sericulture has become widespread globally, and the utilization of artificial diets produces a substantial quantity of silkworm excrement. Although silkworm excrement can be composted for environmentally friendly disposal, the potential utility of the resulting compost remains underexplored. The aim of this study was to assess the quality of this unique compost and screen for eco-beneficial microbes, providing a new perspective on microbial research in waste management, especially in sustainable agriculture. The low-concentration compost application exhibited a greater plant growth-promoting effect, which was attributed to an appropriate nutritional value (N, P, K, and dissolved organic matter) and the presence of plant growth-promoting bacteria (PGPB) within the compost. Encouraged by the "One Health" concept, the eco-benefits of potent PGPB, namely, Klebsiella pneumoniae and Bacillus licheniformis, in sericulture were further evaluated. For plants, K. pneumoniae and B. licheniformis increased plant weight by 152.44 % and 130.91 %, respectively. We also found that even a simple synthetic community composed of the two bacteria performed better than any single bacterium. For animals, K. pneumoniae significantly increased the silkworm (Qiufeng × Baiyu strain) cocoon shell weight by 111.94 %, which could increase sericulture profitability. We also elucidated the mechanism by which K. pneumoniae assisted silkworms in degrading tannic acid, a common plant-derived antifeedant, thereby increasing silkworm feed efficiency. Overall, these findings provide the first data revealing multiple beneficial interactions among silkworm excrement-derived microbes, plants, and animals, highlighting the importance of focusing on microbes in sustainable agriculture.

Dissemination of Ceftriaxone-Resistant Salmonella Enteritidis Harboring Plasmids Encoding blaCTX-M-55 or blaCTX-M-14 Gene in China.

Salmonella Enteritidis was the primary foodborne pathogen responsible for acute gastroenteritis. The growing ceftriaxone resistance poses a significant threat to public health. Infection with S. Enteritidis has emerged as a major public health concern, particularly in developing countries. However, research on ceftriaxone-resistant S. Enteritidis (CRO-RSE) remains limited, particularly concerning its resistance mechanism, plasmid structure, and transmission characteristics. This study aims to address these gaps comprehensively. We collected 235 S. Enteritidis isolates from Hangzhou First People's Hospital between 2010 and 2020. Among these, 8.51% (20/235) exhibited resistance to ceftriaxone. Whole-genome analysis revealed that 20 CRO-RSE isolates harbored blaCTX-M-55 or blaCTX-M-14 on the plasmid. Moreover, the dissemination of the blaCTX-M-type gene was associated with IS26 and ISEcp1. Plasmid fusion entailing the integration of the p1 plasmid with antibiotic resistance genes and the p2 (pSEV) virulence plasmid was observed in certain CRO-RSE. Additionally, the structural analysis of the plasmids unveiled two types carrying the blaCTX-M-type gene: type A with multiple replicons and type B with IncI1 (Alpha) replicon. Type B plasmids exhibited superior adaptability and stability compared to type A plasmids within Enterobacteriaceae. Interestingly, although the type B (S808-p1) plasmid displayed the potential to spread to Acinetobacter baumannii, it failed to maintain stability in this species.

Genetic Characterization of Plasmid-Borne blaOXA-58 and blaOXA-72 in Acinetobacter pittii in Shaanxi, China.

BACKGROUND: Acinetobacter pittii has emerged as an opportunistic nosocomial pathogen associated with hospital-acquired infections. The purpose of this study was to investigate the genetic structures of plasmids carrying carbapenemase genes blaOXA-58 and blaOXA-72 in A. pittii strains AR3676 and AR3651 isolated from patients. METHODS: Antimicrobial susceptibility testing was performed using broth microdilution. Whole-genome sequencing and bioinformatics analysis were performed to characterize the genome of A. pittii AR3676 and AR3651. Conjugation experiments were conducted to evaluate plasmids transferability. Phylogenetic and comparative genomic analysis were performed to explore the characteristics of carbapenem-resistant A. pittii isolates worldwide. RESULTS: The AR3676 strain exhibited resistance to imipenem. The 19,700-bp plasmid pAR3676-OXA-58 harbored blaOXA-58 with genetic contexts consisting of a truncated ISAba3-like-blaOXA58-ISAba3. Additionally, the AR3651 strain exhibited resistance to imipenem and meropenem. The genome of AR3651 comprised one 9,837-bp RepA_AB plasmid pAR3651-OXA-72 harboring blaOXA-72. The blaOXA-72 was flanked by XerC/XerD recombination sites. The conjugation of plasmids pAR3676-OXA-58 and pAR3651-OXA-72 from A. pittii to A. baumannii ATCC 17978RIFR failed three independent times. Phylogenetic analysis of A. pittii strains AR3676, AR3651 and other 504 A. pittii strains collected between 1966 and 2022 from various geographic localities, revealed genetic diversity with a heterogeneous distribution of carbapenemase genes. CONCLUSION: A. pittii strains with plasmid carrying blaOXA-58 or blaOXA-72 may serve as an important reservoir of carbepenemase genes. The carbepenemase genes on a single plasmid may facilitate their dissemination and persistence. Additionally, the pdif sites and mobile elements play an important role in the mobilization of resistance genes and plasmid evolution.

Current trends and possibilities of typical microbial protein production approaches: a review.

Global population growth and demographic restructuring are driving the food and agriculture sectors to provide greater quantities and varieties of food, of which protein resources are particularly important. Traditional animal-source proteins are becoming increasingly difficult to meet the demand of the current consumer market, and the search for alternative protein sources is urgent. Microbial proteins are biomass obtained from nonpathogenic single-celled organisms, such as bacteria, fungi, and microalgae. They contain large amounts of proteins and essential amino acids as well as a variety of other nutritive substances, which are considered to be promising sustainable alternatives to traditional proteins. In this review, typical approaches to microbial protein synthesis processes were highlighted and the characteristics and applications of different types of microbial proteins were described. Bacteria, fungi, and microalgae can be individually or co-cultured to obtain protein-rich biomass using starch-based raw materials, organic wastes, and one-carbon compounds as fermentation substrates. Microbial proteins have been gradually used in practical applications as foods, nutritional supplements, flavor modifiers, and animal feeds. However, further development and application of microbial proteins require more advanced biotechnological support, screening of good strains, and safety considerations. This review contributes to accelerating the practical application of microbial proteins as a promising alternative protein resource and provides a sustainable solution to the food crisis facing the world.

Formation mechanism of a novel core-shell with tetradecyl dimethyl benzyl ammonium-modified montmorillonite interlayer nanofibrous membrane and its antimicrobial properties.

A novel core-shell with a tetradecyl dimethyl benzyl ammonium chloride-modified montmorillonite (TDMBA/MMT) interlayer silk fibroin (SF)/poly(lactic acid) (PLLA) nanofibrous membrane was fabricated using a simple conventional electrospinning method. Scanning electron microscopy and pore size analyses revealed that this core-shell with TDMBA/MMT interlayer maintained its nanofibrous morphology and larger pore structure more successfully than SF/PLLA nanofibrous membranes after treatment with 75% ethanol vapor. Transmission electron microscopy and energy-dispersive X-ray spectroscopy analyses testified that the SF/PLLA-TDMBA/MMT nanofibers exhibited a core-shell with an interlayer structure, with SF/PLLA in the core-shell layer and TDMBA/MMT in the interlayer. The formation of a core-shell with interlayer nanofibers was primarily attributed to the uniform dispersion of TDMBA/MMT nanosheets in a solution owing to its exfoliation using hexafluoroisopropanol and then preparing a stable spinning solution similar to an emulsion. Compared to SF/PLLA nanofibrous membranes, the core-shell structure with TDMBA/MMT interlayers of SF/PLLA nanofibrous membranes exhibited enhanced hydrophilicity, thermal stability, mechanical properties as well as improved and long-lasting antimicrobial performance against Escherichia coli and Staphylococcus aureus without cytotoxicity.

Multifunctional Interface Modification Enables Efficient and Stable HTL-Free Carbon-Electroded CsPbI2Br Perovskite Solar Cells.

In recent years, hole transport layer-free all-inorganic CsPbI2Br carbon-electroded perovskite solar cells (C-PSCs) have garnered significant attention due to a trade-off between stability and photovoltaic performance. However, there are inevitably many defects generated at the surfaces or grain boundaries of CsPbI2Br perovskite films, which will serve as carrier non-radiative recombination centers, and CsPbI2Br perovskite films are sensitive to water molecules to degrade, together with energy level mismatch between CsPbI2Br perovskite and carbon electrodes. Herein, 1-benzyl-3-methylimidazolium hexafluorophosphate (1-B-3-MIMPF6), an imidazolium-based ionic liquid simultaneously containing benzene ring and fluorine atoms, was introduced for the modification of the perovskite/carbon interface. The results showed that it could effectively reduce defects, enhance carrier transfer, mitigate carrier non-radiative recombination, facilitate energy alignment, and block moisture intrusion. Therefore, the photovoltaic performance of the modified PSCs with ITO/SnO2/CsPbI2Br/1-B-3-MIMPF6/carbon architecture has been boosted with a champion power conversion efficiency (PCE) of 13.47 %, open circuit voltage of 1.20 V, short circuit current density of 14.69 mA/cm2, and fill factor of 76 %. Moreover, the unencapsulated modified devices exhibited an improved stability and the PCE maintained 78 % of their initial PCE after 24 h storage at room temperature in a 30 %-35 % humidity environment, whereas that of the pristine devices dropped to almost zero.

Genomic epidemiology and ceftazidime-avibactam high-level resistance mechanisms of Pseudomonas aeruginosa in China from 2010 to 2022.

Ceftazidime-avibactam (CZA) resistance is a huge threat in the clinic; however, the underlying mechanism responsible for high-level CZA resistance in Pseudomonas aeruginosa (PA) isolates remains unknown. In this study, a total of 5,763 P. aeruginosa isolates were collected from 2010 to 2022 to investigate the ceftazidime-avibactam (CZA) high-level resistance mechanisms of Pseudomonas aeruginosa (PA) isolates in China. Fifty-six PER-producing isolates were identified, including 50 isolates carrying blaPER-1 in PA, and 6 isolates carrying blaPER-4. Of these, 82.1% (46/56) were classified as DTR-PA isolates, and 76.79% (43/56) were resistant to CZA. Importantly, blaPER-1 and blaPER-4 overexpression led to 16-fold and >1024-fold increases in the MICs of CZA, respectively. WGS revealed that the blaPER-1 gene was located in two different transferable IncP-2-type plasmids and chromosomes, whereas blaPER-4 was found only on chromosomes and was carried by a class 1 integron embedded in a Tn6485-like transposon. Overexpression of efflux pumps may be associated with high-level CZA resistance in blaPER-1-positive strains. Kinetic parameter analysis revealed that PER-4 exhibited a similar kcat/Km with ceftazidime and a high (∼3359-fold) IC50 value with avibactam compared to PER-1. Our study found that overexpression of PER-1 combined with enhanced efflux pump expression and the low affinity of PER-4 for avibactam contributes to high-level resistance to CZA. Additionally, the Tn6485-like transposon plays a significant role in disseminating blaPER. Urgent active surveillance is required to prevent the further spread of high-level CZA resistance in DTR-PA isolates.

Neoadjuvant savolitinib targeted therapy for stage IIIB-N3 lung adenocarcinoma harboring mesenchymal-epithelial transition exon 14 skipping mutation: a case report and literature review.

Savolitinib is a selective inhibitor that specifically targets the phosphorylation of mesenchymal-epithelial transition (MET) kinase. It has demonstrated significant inhibitory effects on the proliferation of tumor cells with METex14 skipping mutation, making it a promising treatment option. While it is the first approved small-molecule inhibitor specifically targeting MET kinase in China, there is limited information about its efficacy as neoadjuvant therapy for patients with supraclavicular lymph node metastasis (N3). In this case report, we presented the successful outcome of a 48-year-old male patient who was diagnosed with stage IIIB (T2bN3M0) lung adenocarcinoma originating from the left upper lobe. The patient exhibited the METex14 skipping alteration. Following two months of neoadjuvant savolitinib treatment, the patient achieved partial remission, with a significant reduction in the size of the primary tumor and metastatic lymph nodes. Postoperative pathological confirmation revealed a pathological complete response, and subsequent imaging examinations, including computed tomography scan and circulating tumor DNA-based molecular residual disease detection, showed no sign of recurrence at 7 months after surgery. Based on this case, neoadjuvant and adjuvant savolitinib therapy may be considered as a favorable alternative to chemotherapy for marginally resectable nonsmall cell lung cancer patients with METex14 skipping mutation.

Boron-Doped Engineering for Carbon Quantum Dots-Based Memristors with Controllable Memristance Stability.

Carbon quantum dots-based memristors (CQDMs) have emerged as a rising star in data storage and computing. The key constraint to their commercialization is memristance variability, which mainly arises from the disordered conductive paths. Doping methodology can optimize electron and ion transport to help construct a stable conductive mode. Herein, based on boron (B)-doped engineering strategy, three kinds of comparable quantum dots are synthesized, including carbon quantum dots (CQDs), a series of boron-doped CQDs (BCQDs) with different B contents, and boron quantum dots. The corresponding device performances highlight the superiority of BCQDs-based memristors, exhibiting a ternary flash-type memory behavior with longer retention time and more controllable memristance stability. The comprehensive analysis results, including device performance, functional layer morphology, and material simulated calculation, illustrate that the doped B elements can directionally guide the migration of aluminum ions by enhancing the capture of free electrons, resulting in ordered conductive filaments and stable ternary memory behavior. Finally, the conceptual applications of logic display and logic gate are discussed, indicating a bright prospect for BCQDs-based memristors. This work proves that modest B doping can optimize memristance property, establishing a theoretical foundation and template scheme for developing effective and stable CQDMs.

Multiomics analysis reveals the molecular basis for increased body weight in silkworms (Bombyx mori) exposed to environmental concentrations of polystyrene micro- and nanoplastics.

INTRODUCTION: Micro- and nanoplastics (MNPs) are emerging environmental pollutants that have raised serious concerns about their potential impact on ecosystem and organism health. Despite increasing efforts to investigate the impacts of micro- and nanoplastics (MNPs) on biota little is known about their potential impacts on terrestrial organisms, especially insects, at environmental concentrations. OBJECTIVES: To address this gap, we used an insect model, silkworm Bombyx mori to examine the potential long-term impacts of different sizes of polystyrene (PS) MNPs at environmentally realistic concentrations (0.25 to 1.0 µg/mL). METHODS: After exposure to PS-MNPs over most of the larval lifetime (from second to last instar), the endpoints were examined by an integrated physiological (growth and survival) and multiomics approach (metabolomics, 16S rRNA, and transcriptomics). RESULTS: Our results indicated that dietary exposures to PS-MNPs had no lethal effect on survivorship, but interestingly, increased host body weight. Multiomics analysis revealed that PS-MNPs exposure significantly altered multiple pathways, particularly lipid metabolism, leading to enriched energy reserves. Furthermore, the exposure changed the structure and composition of the gut microbiome and increased the abundance of gut bacteria Acinetobacter and Enterococcus. Notably, the predicted functional profiles and metabolite expressions were significantly correlated with bacterial abundance. Importantly, these observed effects were particle size-dependent and were ranked as PS-S (91.92 nm) > PS-M (5.69 µm) > PS-L (9.7 µm). CONCLUSION: Overall, PS-MNPs at environmentally realistic concentrations exerted stimulatory effects on energy metabolism that subsequently enhanced body weight in silkworms, suggesting that chronic PS-MNPs exposure might trigger weight gain in animals and humans by influencing host energy and microbiota homeostasis.

Emergence and plasmid cointegration-based evolution of NDM-1-producing ST107 Citrobacter freundii high-risk resistant clone in China.

Carbapenem-resistant Citrobacter freundii (CRCF) poses an enormous challenge in the health care setting. However, the epidemiology and plasmid dynamic evolution of this species have not been well studied, especially for the novel high-risk resistant clones in the intensive care units (ICUs). Here, we characterised the cointegration-based plasmid dynamic evolution of the emerging ST107 CRCF clone in China. Twenty CRCF strains were identified, including ST22 (30%), ST107 (25%), ST396 (10%) and ST116 (10%). Interestingly, the tigecycline (TGC) resistance gene cluster tmexCD2-toprJ2 and blaNDM-1 and blaKPC-2 were simultaneously found in one ST107 strain. Epidemiological analysis showed that ST107 clone contained human- and environment-derived strains from five countries. Notably, 93.75% (15/16) of the isolates harboured blaNDM-1 or blaKPC-2. Plasmid fusion among various ST107 strains of two patients occurred in the same ICU, mediated by Tn5403 and IS26-based insertion and deletion events. pCF1807-2 carried blaNDM-1 while pCF1807-3 carried both tmexCD2-toprJ2 and blaKPC-2 in the CF1807 strain. Importantly, the cointegrate plasmid pCF1807-2 exhibited higher transfer efficiency and could remain stable after serial passage. Notably, no fitness cost was observed for the host. In conclusion, ST107 CRCF is a high-risk resistant clone due to its ability to integrate resistant plasmids. Our findings elucidated the potential threat and global transmission of the ST107 lineage, and reasonable monitoring should be performed to prevent its further spread in hospitals.

Involvement of plasminogen activator inhibitor-1 in p300/p53-mediated age-related atrial fibrosis.

Plasminogen activator inhibitor-1 (PAI-1), a key regulator of the fibrinolytic system, is also intimately involved in the fibrosis. Although PAI-1 may be involved in the occurrence of atrial fibrillation (AF) and thrombosis in the elderly, but whether it participated in aging-related atrial fibrosis and the detailed mechanism is still unclear. We compared the transcriptomics data of young (passage 4) versus senescent (passage 14) human atrial fibroblasts and found that PAI-1 was closely related to aging-related fibrosis. Aged mice and senescent human and mouse atrial fibroblasts underwent electrophysiological and biochemical studies. We found that p300, p53, and PAI-1 protein expressions were increased in the atrial tissue of aged mice and senescent human and mouse atrial fibroblasts. Curcumin or C646 (p300 inhibitor), or p300 knockdown inhibited the expression of PAI-1 contributing to reduced atrial fibroblasts senescence, atrial fibrosis, and the AF inducibility. Furthermore, p53 knockdown decreased the protein expression of PAI-1 and p21 in senescent human and mouse atrial fibroblasts. Our results suggest that p300/p53/PAI-1 signaling pathway participates in the mechanism of atrial fibrosis induced by aging, which provides new sights into the treatment of elderly AF.

IS26 mediated blaCTX-M-65 amplification in Escherichia coli increase the antibiotic resistance to cephalosporin in vivo.

OBJECTIVES: To characterize two Escherichia coli strains isolated from a patient pre- and post-treatment, using ß-lactams and ß-lactam/ß-lactamase inhibitor combinations (BLBLIs). METHODS: A combination of antibiotic susceptibility testing (AST) with whole genome sequencing using Illumina and Oxford Nanopore platforms. Long-read sequencing and reverse transcription-quantitative PCR were performed to determine the copy numbers and expression levels of antibiotic resistance genes (ARGs), respectively. Effect on fitness costs were assessed by growth rate determination. RESULTS: The strain obtained from the patient after the antibiotic treatment (XH989) exhibited higher resistance to cefepime, BLBLIs and quinolones compared with the pre-treatment strain (XH987). Sequencing revealed IS26-mediated duplications of a IS26-fosA3-blaCTX-M-65 plasmid-embedded element in strain XH989. Long-read sequencing (7.4 G data volume) indicated a variation in copy numbers of blaCTX-M-65 within one single culture of strain XH989. Increased copy numbers of the IS26-fosA3-blaCTX-M-65 element were correlated with higher CTX-M-65 expression level and did not impose fitness costs, while facilitating faster growth under high antibiotic concentrations. CONCLUSION: Our study is an example from the clinic how BLBLIs and ß-lactams exposure in vivo possibly promoted the amplification of an IS26-multiple drug resistance (MDR) region. The observation of a copy number variation seen with the blaCTX-M-65 gene in the plasmid of the post-treatment strain expands our knowledge of insertion sequence dynamics and evolution during treatment.

Resource recovery and valorization of food wastewater for sustainable development: An overview of current approaches.

The food processing industry is one of the world's largest consumers of potable water. Agri-food wastewater systems consume about 70% of the world's fresh water and cause at least 80% of deforestation. Food wastewater is characterized by complex composition, a wide range of pollutants, and fluctuating water quality, which can cause huge environmental pollution problems if discharged directly. In recent years, food wastewater has attracted considerable attention as it is considered to have great prospects for resource recovery and reuse due to its rich residues of nutrients and low levels of harmful substances. This review explored and compared the sources and characteristics of different types of food wastewater and methods of wastewater treatment. Particular attention was paid to the different methods of resource recovery and reuse of food wastewater. The diversity of raw materials in the food industry leads to different compositional characteristics of wastewater, which determine the choice and efficiency of wastewater treatment methods. Physicochemical methods, and biological methods alone or in combination have been used for the efficient treatment of food wastewater. Current approaches for recycling and reuse of food wastewater include culture substrates, agricultural irrigation, and bio-organic fertilizers, recovery of high-value products such as proteins, lipids, biopolymers, and bioenergy to alleviate the energy crisis. Food wastewater is a promising substrate for resource recovery and reuse, and its valorization meets the current international policy requirements regarding food waste and environment protection, follows the development trend of the food industry, and is also conducive to energy conservation, emission reduction, and economic development. However, more innovative biotechnologies are necessary to advance the effectiveness of food wastewater treatment and the extent of resource recovery and valorization.

A review on takeaway packaging waste: Types, ecological impact, and disposal route.

Rapid economic growth and urbanization have led to significant changes in the world's consumption patterns. Accelerated urbanization, the spread of the mobile Internet, and the increasing pace of work globally have all contributed to the demand for the food takeaway industry. The rapid development of the takeaway industry inevitably brings convenience to life, and with it comes great environmental pressure from waste packaging materials. While maintaining the convenience of people's lives, further reducing the environmental pollution caused by takeaway packaging materials and promoting the recycling and reuse of takeaway packaging waste need to attract the attention and concern of the whole society. This review systematically and comprehensively introduces common takeaway food types and commonly used packaging materials, analyzes the impacts of discarded takeaway packaging materials on human health and the ecological environment, summarizes the formulation and implementation of relevant policies and regulations, proposes treatment methods and resourceful reuse pathways for discarded takeaway packaging, and also provides an outlook on the development of green takeaway packaging. Currently, only 20% of waste packaging materials are recycled worldwide, and there is still a need to develop more green takeaway packaging materials and continuously improve relevant policies and regulations to promote the sustainable development of the takeaway industry. The review is conducive to further optimizing the takeaway packaging management system, alleviating the environmental pollution problem, and providing feasible solutions and technical guidance for further optimizing takeaway food packaging materials and comprehensive utilization of resources.

Genotypic characterization of a Proteus mirabilis strain harboring blaKPC-2 on the IncN plasmid isolated from a patient with bloodstream infection in China.

BACKGROUND: Carbapenemase is the predominant enzyme in the mechanism leading to Enterobacterales resistance to carbapenems, and the rapid spread of the blaKPC gene is a major public health concern. Here, we describe a carbapenem-resistant Proteus mirabilis strain XH983, which harbored a blaKPC-2-producing IncN plasmid, isolated from a bloodstream infection. METHODS: Whole-genome sequencing and bioinformatics analysis were performed to assess the genetic environment of P. mirabilis XH983. Conjugation and transfer experiments were performed and the corresponding strains were confirmed by antimicrobial susceptibility testing. Phylogenetic and comparative genomic analysis were performed to explore the characteristics of carbapenem-resistant P. mirabilis isolates worldwide. RESULTS: P. mirabilis XH983 was isolated from the blood of a patient in Hangzhou, China. The genome of XH983 contained one 4128,916 bp circular chromosome and one 24,225 bp IncN plasmid harboring blaKPC-2. P. mirabilis XH983 had multiple resistance genes, conferring resistance to aminoglycosides [aph(3')-Ia, aph(3'')-Ib, aph(6)-Id, aac(3)-IId, aadA5, aadA1], ß-lactams (blaKPC-2, blaTEM-1B), phenicol (cat, catA1), sulphonamide/trimethoprim (drfA1, drfA17, sul1, sul2) and tetracycline [tet(J)]. The phylogenetic tree showed that XH983 was present in a cluster of 30 isolates, all of which carried blaKPC-2 and most of them came from the same hospital as XH983, indicating the clonal spread of the cluster. CONCLUSION: We characterized carbapenem-resistant P. mirabilis clinical isolate XH983. The genome sequence of P. mirabilis XH983 provides information about resistance mechanisms of P. mirabilis carrying the blaKPC-2 plasmid and the potential spread of blaKPC-2.

Alteration of adeS Contributes to Tigecycline Resistance and Collateral Sensitivity to Sulbactam in Acinetobacter baumannii.

The treatment of extensively drug-resistant (XDR) A. baumannii has emerged as a major problem. Tigecycline (TGC) and sulbactam (SUL) are both effective antibiotics against XDR A. baumannii. Here, we investigated the in-host evolution and mechanism of collateral sensitivity (CS) phenomenon in development of tigecycline resistance accompanied by a concomitant increase of sulbactam susceptibility. A total of four XDR A. baumannii strains were sequentially isolated from the same patient suffering from bacteremia. Core-genome multilocus sequence typing separated all the strains into two clusters. Comparative analysis of isolate pair 1 revealed that multiplication of blaOXA-23 within Tn2006 on the chromosome contributed to the change in the antimicrobial susceptibility phenotype of isolate pair 1. Additionally, we observed the emergence of CS to sulbactam in isolate pair 2, as demonstrated by an 8-fold increase in the TGC MIC with a simultaneous 4-fold decrease in the SUL MIC. Compared to the parental strain Ab-3557, YZM-0406 showed partial deletion in the two-component system sensor adeS. Reconstruction of the adeS mutant in Ab-3557 in situ suggested that TGC resistance and CS to SUL were mainly caused by the mutation of adeS. Overall, our study reported a novel CS combination of TGC and SUL in A. baumannii and further revealed a mechanism of CS attributed to the mutation of adeS. This study provides a valuable foundation for developing effective regimens and sequential combinations of tigecycline and sulbactam against XDR A. baumannii. IMPORTANCE Collateral sensitivity (CS) has become an increasingly common evolutionary trade-off during adaptive bacterial evolution. Here, we report a novel combination of tigecycline (TGC) resistance and CS to sulbactam (SUL) in A. baumannii. TGC and SUL are both effective antibiotics against XDR A. baumannii, and it is essential to reveal the mechanism of CS between TGC and SUL. In our study, the partial deletion of adeS, a two-component system sensor, was confirmed to be the key factor contributing to this CS phenomenon. This study provides a valuable foundation for developing effective regimens and sequential combinations of tigecycline and sulbactam against XDR A. baumannii.

Noah: Reinforcement-Learning-Based Rate Limiter for Microservices in Large-Scale E-Commerce Services.

Modern large-scale online service providers typically deploy microservices into containers to achieve flexible service management. One critical problem in such container-based microservice architectures is to control the arrival rate of requests in the containers to avoid containers from being overloaded. In this article, we present our experience of rate limit for the containers in Alibaba, one of the largest e-commerce services in the world. Given the highly diverse characteristics of containers in Alibaba, we point out that the existing rate limit mechanisms cannot meet our demand. Thus, we design Noah, a dynamic rate limiter that can automatically adapt to the specific characteristic of each container without human efforts. The key idea of Noah is to use deep reinforcement learning (DRL) that automatically infers the most suitable configuration for each container. To fully embrace the advantages of DRL in our context, Noah addresses two technical challenges. First, Noah uses a lightweight system monitoring mechanism to collect container status. In this way, it minimizes the monitoring overhead while ensuring a timely reaction to system load changes. Second, Noah injects synthetic extreme data when training its models. Thus, its model gains knowledge on unseen special events and hence remains highly available in extreme scenarios. To guarantee model convergence with the injected training data, Noah adopts task-specific curriculum learning to train the model from normal data to extreme data gradually. Noah has been deployed in the production of Alibaba for two years, serving more than 50000 containers and around 300 types of microservice applications. Experimental results show that Noah can well adapt to three common scenarios in the production environment. It effectively achieves better system availability and shorter request response time compared with four state-of-the-art rate limiters.

Solar-Powered Interfacial Evaporation and Deicing Based on a 3D-Printed Multiscale Hierarchical Design.

Solar-powered interfacial heating has emerged as a sustainable technology for hybrid applications with minimal carbon footprints. Aerogels, hydrogels, and sponges/foams are the main building blocks for state-of-the-art photothermal materials. However, these conventional three-dimensional (3D) structures and related fabrication technologies intrinsically fail to maximize important performance-enhancing strategies and this technology still faces several performance roadblocks. Herein, monolithic, self-standing, and durable aerogel matrices are developed based on composite photothermal inks and ink-extrusion 3D printing, delivering all-in-one interfacial steam generators (SGs). Rapid prototyping of multiscale hierarchical structures synergistically reduce the energy demand for evaporation, expand actual evaporation areas, generate massive environmental energy input, and improve mass flows. Under 1 sun, high water evaporation rates of 3.74 kg m-2 h-1 in calm air and 25.3 kg m-2 h-1 at a gentle breeze of 2 m s-1 are achieved, ranking among the best-performing solar-powered interfacial SGs. 3D-printed microchannels and hydrophobic modification deliver an icephobic surface of the aerogels, leading to self-propelled and rapid removal of ice droplets. This work shines light on rational fabrication of hierarchical photothermal materials, not merely breaking through the constraints of solar-powered interfacial evaporation and clean water production, but also discovering new functions for photothermal interfacial deicing.

Identification of Antibiotic Resistance in ESKAPE Pathogens through Plasmonic Nanosensors and Machine Learning.

Antibiotic-resistant ESKAPE pathogens cause nosocomial infections that lead to huge morbidity and mortality worldwide. Rapid identification of antibiotic resistance is vital for the prevention and control of nosocomial infections. However, current techniques like genotype identification and antibiotic susceptibility testing are generally time-consuming and require large-scale equipment. Herein, we develop a rapid, facile, and sensitive technique to determine the antibiotic resistance phenotype among ESKAPE pathogens through plasmonic nanosensors and machine learning. Key to this technique is the plasmonic sensor array that contains gold nanoparticles functionalized with peptides differing in hydrophobicity and surface charge. The plasmonic nanosensors can interact with pathogens to generate bacterial fingerprints that alter the surface plasmon resonance (SPR) spectra of nanoparticles. In combination with machine learning, it enables the identification of antibiotic resistance among 12 ESKAPE pathogens in less than 20 min with an overall accuracy of 89.74%. This machine-learning-based approach allows for the identification of antibiotic-resistant pathogens from patients and holds great promise as a clinical tool for biomedical diagnosis.