Mobilizable antibiotic resistance genes are present in dust microbial communities.

The decades-long global trend of urbanization has led to a population that spends increasing amounts of time indoors. Exposure to microbes in buildings, and specifically in dust, is thus also increasing, and has been linked to various health outcomes and to antibiotic resistance genes (ARGs). These are most efficiently screened using DNA sequencing, but this method does not determine which microbes are viable, nor does it reveal whether their ARGs can actually disseminate to other microbes. We have thus performed the first study to: 1) examine the potential for ARG dissemination in indoor dust microbial communities, and 2) validate the presence of detected mobile ARGs in viable dust bacteria. Specifically, we integrated 166 dust metagenomes from 43 different buildings. Sequences were assembled, annotated, and screened for potential integrons, transposons, plasmids, and associated ARGs. The same dust samples were further investigated using cultivation and isolate genome and plasmid sequencing. Potential ARGs were detected in dust isolate genomes, and we confirmed their placement on mobile genetic elements using long-read sequencing. We found 183 ARGs, of which 52 were potentially mobile (associated with a putative plasmid, transposon or integron). One dust isolate related to Staphylococcus equorum proved to contain a plasmid carrying an ARG that was detected metagenomically and confirmed through whole genome and plasmid sequencing. This study thus highlights the power of combining cultivation with metagenomics to assess the risk of potentially mobile ARGs for public health.

Metal-Free Transformation of Sulfonyl Oxime Ethers with Amines to Oxime Ethers.

Sulfonyl oxime ethers undergo facile radical substitutions with various amines to yield the corresponding oxime ethers. An efficient arylation of sulfonyl oxime ethers was accomplished under ambient temperature and metal-free conditions, with a wide range of functional group tolerance. Mechanistic investigations indicate that a phenyl radical is involved in the catalytic cycle.

Impacts of indoor surface finishes on bacterial viability.

Microbes in indoor environments are constantly being exposed to antimicrobial surface finishes. Many are rendered non-viable after spending extended periods of time under low-moisture, low-nutrient surface conditions, regardless of whether those surfaces have been amended with antimicrobial chemicals. However, some microorganisms remain viable even after prolonged exposure to these hostile conditions. Work with specific model pathogens makes it difficult to draw general conclusions about how chemical and physical properties of surfaces affect microbes. Here, we explore the survival of a synthetic community of non-model microorganisms isolated from built environments following exposure to three chemically and physically distinct surface finishes. Our findings demonstrated the differences in bacterial survival associated with three chemically and physically distinct materials. Alkaline clay surfaces select for an alkaliphilic bacterium, Kocuria rosea, whereas acidic mold-resistant paint favors Bacillus timonensis, a Gram-negative spore-forming bacterium that also survives on antimicrobial surfaces after 24 hours of exposure. Additionally, antibiotic-resistant Pantoea allii did not exhibit prolonged retention on antimicrobial surfaces. Our controlled microcosm experiment integrates measurement of indoor chemistry and microbiology to elucidate the complex biochemical interactions that influence the indoor microbiome.

From one species to another: A review on the interaction between chemistry and microbiology in relation to cleaning in the built environment.

Since the advent of soap, personal hygiene practices have revolved around removal, sterilization, and disinfection-both of visible soil and microscopic organisms-for a myriad of cultural, aesthetic, or health-related reasons. Cleaning methods and products vary widely in their recommended use, effectiveness, risk to users or building occupants, environmental sustainability, and ecological impact. Advancements in science and technology have facilitated in-depth analyses of the indoor microbiome, and studies in this field suggest that the traditional "scorched-earth cleaning" mentality-that surfaces must be completely sterilized and prevent microbial establishment-may contribute to long-term human health consequences. Moreover, the materials, products, activities, and microbial communities indoors all contribute to, or remove, chemical species to the indoor environment. This review examines the effects of cleaning with respect to the interaction of chemistry, indoor microbiology, and human health.

Design, synthesis and cytotoxic activities of scopoletin-isoxazole and scopoletin-pyrazole hybrids.

12 novel scopoletin-isoxazole and scopoletin-pyrazole hybrids were designed, synthesized and their chemical structures were confirmed by HR-MS, IR, 1H NMR and 13C NMR spectra. The anticancer activities of the newly synthesized compounds were evaluated in vitro against three human cancer cell lines including HCT-116, Hun7 and SW620 by MTT assay. The screening results showed that six compounds (9a, 9c, 9d, 12a, 18b and 18d) exhibited potent cytotoxic activities with IC50 values below 20µM. Besides, we have further evaluated the growth inhibitory activities of six compounds against the human normal tissue cell lines HFL-1. Especially, compound 9d displayed significant anti-proliferative activity with IC50 values ranging from 8.76µM to 9.83µM and weak cytotoxicity with IC50 value of 90.9µM on normal cells HFL-1, which suggested that isoxazole-based hybrids of scopoletin were an effective chemical modification to improve the anticancer activity of scopoletin.

Acupuncture and related therapies for tension-type headache: a systematic review and network meta-analysis.

Background: Tension-type headache (TTH) is one of the most common primary headaches. Several studies have confirmed the efficacy of acupuncture therapies for TTH, but it is uncertain which treatment is most effective. Objective: This study aimed to compare the effectiveness and safety of different acupuncture therapies for TTH using Bayesian Network Meta-analysis to provide new ideas for treating TTH. Methods: Nine databases were searched for randomized controlled trials (RCTs) about different acupuncture therapies for TTH up to December 1, 2022. The outcome indicators analyzed in our study were total effective rate, visual analog scale (VAS), headache frequency, and safety. Pairwise meta-analysis and risk of bias assessment were performed using Review Manager 5.4. Stata 15.0 generated a network evidence plot and detected publication bias. Finally, a Bayesian network meta-analysis of the data was used by RStudio. Results: The screening process resulted in 30 RCTs that met the inclusion criteria, including 2,722 patients. Most studies failed to report details of trials and were therefore assessed as unclear risks. Two studies were considered high risk because they did not report on all pre-specified outcome indicators or had incomplete data on outcome indicators. The NMA results showed that for total effective rate, bloodletting therapy had the most considerable SUCRA value (0.93156136), for VAS, head acupuncture combined with Western medicine ranked first (SUCRA = 0.89523571), and acupuncture combined with herbal medicine was the most effective in improving headache frequency (p > 0.05). Conclusion: Acupuncture can be used as one of the complementary or alternative therapies for TTH; bloodletting therapy better improves the overall symptoms of TTH, head acupuncture combined with Western medicine is more effective in reducing VAS scores, and acupuncture combined with herbal medicine seems to reduce headache frequency, but the difference is not statistically significant. Overall, acupuncture for TTH is effective with mild side effects, but future high-quality studies are still necessary. Systematic review registration: https://www.crd.york.ac.uk/prospero/, PROSPERO [CRD42022368749].

Clinical efficacy of different shoulder joint drug injections for rotator cuff injuries: A network meta-analysis.

BACKGROUND: Rotator cuff injury is a common clinical disorder of the musculoskeletal system. It is one of the most common causes of shoulder pain and shoulder joint dysfunction. Intra-articular injection therapy is one of the common conservative treatments for rotator cuff injury in clinical practice, but scholars have been controversial about the different drugs used for injection therapy and their clinical effectiveness, and there is no complete agreement on the choice of different injectables, and the existing original studies are mostly direct comparisons in 1 arm, lacking indirect comparisons, making it difficult to have a clear and comprehensive understanding. OBJECTIVE: A network Meta-analysis was used to comprehensively compare the effectiveness of drug injection therapies for rotator cuff injuries. METHODS: The PubMed, The Cochrane Library, EMbase, Chinese national knowledge infrastructure, Chinese BioMedical Literature on disc, China Science and Technology Journal Database, and Wan-Fang databases were searched for randomized controlled trials on the effectiveness of steroid injections for the comparative treatment of rotator cuff injury for the period April 19, 2013 to April 19, 2022 (the last decade). Two investigators independently screened the literature, extracted data according to inclusion and exclusion criteria, and evaluated the quality of the literature in parallel. Statistical analysis was performed using Stata 16.0 software to compare the differences in efficacy of each treatment measure and rank the efficacy using the ratio and 95% confidence interval (CI) as the effect indicator. RESULTS: 10 RCTs with a total of 861 patients with rotator cuff injury were included, involving 4 therapeutic measures: corticosteroid injection therapy (COR), platelet-rich plasma injection therapy (PRP), Hyaluronic acid injection therapy (HA), and prolotherapy therapy (PRO).Meta-analysis results showed that the ranking results of the 4 therapeutic measures were: corticosteroid injection + hyaluronic acid injection > platelet-rich plasma injection + corticosteroid injection > corticosteroid injection > platelet-rich plasma injection > PRO > platelet-rich plasma injection + hyaluronic acid injection > hyaluronic acid injection. CONCLUSION: we recommend that corticosteroid injections combined with hyaluronic acid injections can be used for the non-surgical conservative clinical management of rotator cuff injuries.

Clinically relevant pathogens on surfaces display differences in survival and transcriptomic response in relation to probiotic and traditional cleaning strategies.

Indoor surfaces are paradoxically presumed to be both colonized by pathogens, necessitating disinfection, and "microbial wastelands." In these resource-poor, dry environments, competition and decay are thought to be important drivers of microbial community composition. However, the relative contributions of these two processes have not been specifically evaluated. To bridge this knowledge gap, we used microcosms to evaluate whether interspecies interactions occur on surfaces. We combined transcriptomics and traditional microbiology techniques to investigate whether competition occurred between two clinically important pathogens, Acinetobacter baumannii and Klebsiella pneumoniae, and a probiotic cleaner containing a consortium of Bacillus species. Probiotic cleaning seeks to take advantage of ecological principles such as competitive exclusion, thus using benign microorganisms to inhibit viable pathogens, but there is limited evidence that competitive exclusion in fact occurs in environments of interest (i.e., indoor surfaces). Our results indicate that competition in this setting has a negligible impact on community composition but may influence the functions expressed by active organisms. Although Bacillus spp. remained viable on surfaces for an extended period of time after application, viable colony forming units (CFUs) of A. baumannii recovered following exposure to a chemical-based detergent with and without Bacillus spp. showed no statistical difference. Similarly, for K. pneumoniae, there were small statistical differences in CFUs between cleaning scenarios with or without Bacillus spp. in the chemical-based detergent. The transcriptome of A. baumannii with and without Bacillus spp. exposure shared a high degree of similarity in overall gene expression, but the transcriptome of K. pneumoniae differed in overall gene expression, including reduced response in genes related to antimicrobial resistance. Together, these results highlight the need to fully understand the underlying biological and ecological mechanisms for community assembly and function on indoor surfaces, as well as having practical implications for cleaning and disinfection strategies for infection prevention.

Towards understanding microbial degradation of chloroquine in large saltwater systems.

Circulating saltwater aquariums hosting marine animals contain a wide range of microorganisms, which have strong implications on promoting animal health. In this study, we investigated the degradation of chloroquine phosphate, an anti-parasitic bath pharmaceutical used in saltwater quarantine and exhibition systems, and attributed the reduction in drug concentration to microbial degradation of chloroquine associated with pipeline microbial communities. To advance our knowledge on chloroquine degradation in aquatic systems, we conducted microbial and chemical analyses on three tropical saltwater systems. Our findings show that aquarium microbiome composition is shaped by sampling location (i.e., tank water and pipeline; PERMANOVA R2 = 0.09992, p = 0.0134), chloroquine dosing (PERMANOVA R2 = 0.05700, p = 0.0030), and whether the aquarium is occupied by marine animals (PERMANOVA R2 = 0.07019, p = 0.0009). Several microbial taxa belonging to the phyla Actinobacteria, Bacteroidetes, Chloroflexi, and Proteobacteria, along with functional genes related to pathways such as phenylethylamine degradation and denitrification, appeared to have differential (relative) abundance between samples where chloroquine degradation was observed and those without degradation (Benjamini-Hochberg adjusted p-value <0.05). Together, these results provide practical mitigation options to prevent or delay the development of chloroquine-degrading microbial communities in saltwater aquariums. Our results further demonstrate the need to improve our understanding of the interactions between nitrogen availability and microbial activity in saltwater systems.

Anthropogenic chemicals and their impacts on microbes living in buildings.

Humans spend the vast majority of their time indoors where complex interactions occur among indoor anthropogenic chemicals, indoor microbiomes and human occupants. This paper summarizes previous work addressing interactions between anthropogenic chemicals associated with indoor household products and building materials, and microorganisms found within the built environment. Water availability seems to determine the extent to which microbes are impacted by anthropogenic chemicals, since desiccation remains one of the primary stressors regulating microbial viability indoors. Several lines of evidence suggest that both fungi and bacteria are capable of transforming biodegradable ingredients originating from various products used indoors when water is present. Previous research also establishes positive and significant correlations between anthropogenic chemicals that are antimicrobial and antibiotic resistance gene abundance. As researchers move towards understanding complex indoor environments as well as the role of anthropogenic chemicals in shaping microbiomes, in situ activities associated with the viable indoor microbial population merit more attention.

Implications of indoor microbial ecology and evolution on antibiotic resistance.

The indoor environment is an important source of microbial exposures for its human occupants. While we naturally want to favor positive health outcomes, built environment design and operation may counter-intuitively favor negative health outcomes, particularly with regard to antibiotic resistance. Indoor environments contain microbes from both human and non-human origins, providing a unique venue for microbial interactions, including horizontal gene transfer. Furthermore, stressors present in the built environment could favor the exchange of genetic material in general and the retention of antibiotic resistance genes in particular. Intrinsic and acquired antibiotic resistance both pose a potential threat to human health; these phenomena need to be considered and controlled separately. The presence of both environmental and human-associated microbes, along with their associated antibiotic resistance genes, in the face of stressors, including antimicrobial chemicals, creates a unique opportunity for the undesirable spread of antibiotic resistance. In this review, we summarize studies and findings related to various interactions between human-associated bacteria, environmental bacteria, and built environment conditions, and particularly their relation to antibiotic resistance, aiming to guide "healthy" building design.

Nano-enabled, antimicrobial toothbrushes - How physical and chemical properties relate to antibacterial capabilities.

Over the past two decades, Ag and Zn nanoparticles have been integrated into various consumer products as a biocide. While some nano-enabled consumer products have been shown to have antibacterial properties, their antibacterial efficacy as well as the human and environmental health outcomes are not fully known. In this study, we examine a nanoparticle-enabled product that also serves as a conduit for human exposure to bacteria: toothbrushes. We utilize a combination of chemical analyses, laboratory experiments, and microscopy to characterize the nano-enabled toothbrush bristles. Our analysis showed the majority of measured Ag and Zn particles ranged from approximately 50 to 100 nm in size and were located on the surface and within bristles. During simulated brushing, antimicrobial bristles released both Ag and Zn, the majority of which was released in particulate form. While our results demonstrate that antimicrobial bristles have enhanced bactericidal properties compared to control samples, we also show that the surface topography influences nanoparticle retention, microbial adhesion, and bactericidal activity. We thus conclude that Ag or Zn content alone is insufficient to predict antimicrobial properties, which are further governed by the bioavailability of Ag or Zn at the bristle surface.

Efficacy of compatible acupoints and single acupoint versus sham acupuncture for functional dyspepsia: study protocol for a randomized controlled trial.

BACKGROUND: Acupoint selection is a key factor in the treatment of diseases and has not been well studied. The aim of this trial is to explore the differences in efficacy between compatible acupoints and a single acupoint for patients with functional dyspepsia (FD). METHODS: This randomized controlled trial will be conducted in the First Affiliated Hospital of Changchun University of Chinese Medicine in China. Two hundred and sixteen FD patients will be randomly assigned to the compatible acupoints group, single acupoint group, or sham acupuncture group. This trial will include a 1-week baseline period, a 4-week treatment period, and a 4-week follow-up period. During the 4-week treatment period, patients will receive 20 sessions of acupuncture (weekly cycles of one session per day for 5 consecutive days followed by a 2-day break). The primary outcome will be a change in the Nepean Dyspepsia Life Quality Index from baseline to after the 4-week treatment period. Secondary outcome measures will include the dyspeptic symptom sum score, Overall Treatment Effect questionnaire, and 36-item Short Form survey. Adverse events also will be recorded. Ultraweak photon emission and metabolomics tests will be performed at baseline and at the end of treatment to explore the mechanisms of the differences between compatible acupoints and a single acupoint. DISCUSSION: The results of this trial will allow us to compare the difference in efficacy between compatible acupoints and a single acupoint. The findings from this trial will be published in peer-reviewed journals. TRIAL REGISTRATION: Acupuncture-Moxibustion Clinical Trial Registry, AMCTR-IPC-18000176, registered on 4 March 2019; Chinese Clinical Trial Registry, ChiCTR1900023983, registered on 23 June 2019.

Synthesis, in vitro and in vivo antitumor activity of scopoletin-cinnamic acid hybrids.

A series of hybrids of scopoletin and substituted cinnamic acid were designed, synthesized and evaluated in vitro and in vivo against five human tumor cell lines [MCF-7, MDA-MB-231, A549, HCT-116, and HeLa] with doxorubicin as the positive control. Compounds 17a, 17b, 17c and 17g exhibited potent cytotoxic activity. Especially, compound 17b displayed broad spectrum activity with IC50 values ranging from 0.249 µM to 0.684 µM. Moreover, in a preliminary pharmacological study, 17b not only remarkably induced cellular apoptosis, but also clearly induced A549 cells cycle arrest at S phase. In vivo study showed that 17b significantly suppressed tumor growth in a dose-dependent manner without causing the loss of the mean body weight of mice, which was superior to doxorubicin. These preliminary results indicate that 17b is an optimal anti-cancer leading compound and merit further structural modification.