搜索结果：Nature microbiology

Nature builds functional materials through simple yet powerful processes that generate structured architecture across scales-from the lamellar patterns in seashells to the zonal organization of living tissues. Emulating such complexity in engineered systems remains challenging and often requires microfabricated components, external fields, or specialized hardware. Previously, we introduced chaotic printing as a deterministic and flow- and geometry-driven strategy for fabricating structured filaments, using static mixers embedded within extrusion printheads-primarily in the context of biofabrication. We broaden the architectural and functional scope of chaotic printing by exploring diverse static mixer designs and demonstrating its compatibility with three distinct deposition modes: wet-printing, dripping, and direct ink writing. These modalities enable the generation of material constructs with chemically and biologically relevant internal organization. We showcase examples ranging from zonally arranged mammalian cells that prefigure microtissue compartments to spatially patterned bacterial consortia composed of strict and facultative anaerobes and localized mineral precipitation within hydrogel filaments. These proof-of-concept-demonstrations underscore the potential of chaotic printing for fabricating structured soft matter where internal microarchitecture enables biologically and chemically relevant processes. This study positions chaotic printing as a modular, scalable, accessible platform for generating architected materials across fields ranging from cell culture and microbiology to functional soft materials.

Phospholipases D (PLDs) are lipolytic enzymes that catalyze hydrolysis of the distal phosphodiester bond of various membrane phospholipids (PLs). These enzymes generate invariant phosphatidic acid (PA) and a polar head group whose nature depends on the PL substrate. PA is both a key metabolic intermediate in the synthesis of lipids and a second messenger involved in diverse processes, including cellular signaling, development of cancer in mammals, bacterial pathogenesis, and defense responses in plants. Regarding the diversity of PL nature and composition, all PLDs described so far can act on several PLs. Furthermore, the molecular determinants of PL recognition by PLDs and the preference of one PL over another remain poorly understood. We previously described the biochemical characterization of a PLD, called DaPLD1, from the bacterium Dechloromonas aromatica RCB. This PLD did indeed have a strong preference for phosphatidylethanolamine (PE) over all other PLs but was also able to hydrolyze phosphatidylcholine (PC). Here, we identified a second PLD called DaPLD2, which shares only 38% peptide identity with DaPLD1. We have recombinantly expressed this PLD in Escherichia coli and characterized it biochemically. Unlike DaPLD1, DaPLD2 exhibits an exclusive specificity for PE and is inactive toward other PLs, including PC. DaPLD2 is distant phylogenetically from DaPLD1 but shares common features and key residues found in bacterial PLDs. Altogether, this unique property of DaPLD2 towards PE provides valuable insights into PL metabolism in bacteria and holds potential for development as a tool enzyme to selectively transform PE among other PLs.

Actinomyces europaeus is an emerging Gram-positive bacterium associated with skin and soft tissue infections. It exhibits intrinsic resistance to multiple antibiotics, and its fastidious growth and the polymicrobial nature of infections often delay diagnosis and treatment. This report highlights a rare case of A. europaeus infection following elective surgery. A 78-year-old woman presented with asthenia and purulent umbilical discharge two months after abdominoplasty. A CT scan revealed a large supra-fascial fluid collection. She underwent surgical debridement and lavage. Cultures identified Actinomyces europaeus, alongside Staphylococcus hominis and Staphylococcus haemolyticus. Susceptibility testing for A. europaeus was not performed. Following infectious disease consultation, therapy was switched from piperacillin/tazobactam to intravenous penicillin G, transitioning to oral amoxicillin/clavulanic acid for 12 weeks. The patient recovered fully with no recurrence. A review of the literature, highlights that A. europaeus infections are often polymicrobial, require advanced diagnostics such as MALDI-TOF (matrix-assisted laser desorption/ionization time of flight), and respond favourably to penicillin-based therapy when combined with complete surgical debridement. This case and literature review underscore challenges in managing A. europaeus and emphasize the need for increased awareness and standardized therapeutic guidelines.

Dominant anti-infective strategies equate therapeutic success with pathogen eradication, yet in the gut most clinically relevant "pathogens" are pathobionts that cause disease only under specific ecological conditions. Antibiotics resolve infection but decimate commensal communities and select for resistance. We review antibody-based interventions, native mucosal antibodies (IgA, IgM), monoclonal antibodies, and immunoglobulin Y (IgY), as mechanistic test cases for a functional silencing paradigm, in which pathobiont virulence is attenuated through non-bactericidal mechanisms while preserving community architecture. Drawing on randomized trial data (bezlotoxumab in Clostridioides difficile recurrence prevention, MODIFY I/II, n = 2,655), preclinical and early clinical IgY studies in enteric infections, and long-term IgY deployment in aquaculture, we find that functional silencing delivers durable benefit when disease is driven by discrete virulence factors. However, evolutionary risks, including phase variation, conformational switching, and the theoretical framework of "imperfect immunity", identify conditions under which retained pathobionts may re-emerge as threats. Eradication and functional silencing are best understood as complementary strategies whose optimal deployment depends on host immune status, barrier integrity, and the nature of pathobiont virulence. Defining the boundary between safe coexistence and evolutionary rebound constitutes the field's central unresolved challenge.

Enteric methane emissions from ruminant livestock contribute to global warming, creating an urgent need for effective mitigation strategies that do not compromise animal productivity and welfare. Methanogenic archaea within the rumen microbiome drive enteric methane emissions. However, large-scale rumen-fluid sampling in commercial production systems is impractical, due to its invasive nature and the associated logistical challenges. This study hypothesized that rumination facilitates the capture of rumen microbial signals within the oral cavity, therefore oral microbiome profiles can be a practical alternative for explaining variation in methane emissions commercial production systems. To test the hypothesis, we estimated the oral microbiability, defined as the proportion of phenotypic variance in methane emissions explained by oral microbiome variation. Samples were collected from 209 tropical composite beef cattle across two trials in Queensland, Australia. Oral microbiome samples were obtained from all animals, with paired rumen samples in one trial, and methane emissions were measured using either the sulfur hexafluoride tracer technique or the GreenFeed system. Microbial features were characterized using taxonomic and functional annotations, and microbiability was estimated using mixed linear models incorporating microbiome-based relationship matrices. The oral microbiability reported in this study ranged from 0.27 to 0.63 with standard errors 0.12 to 0.25. Functional microbial profiles explained a numerically greater proportion of methane emission variation than taxonomic profiles in some comparisons, however, the differences were not statistically significant due to large standard errors. These findings demonstrated that oral microbiome sampling provides a practical and scalable proxy method for capturing variation in methane emissions among the individual cattle in grazing systems, where direct methane gas measurements are labor-intensive and difficult to implement. Therefore, further validation of oral microbiability against methane emissions measured in larger animal cohorts is required. Such validation would enable a more robust assessment of the predictive accuracy of oral microbiome-based models while accounting for additional sources of variation, including host genetic, environmental, and management factors, which could not be fully addressed in the present study. Cattle produce methane as part of their normal digestion and this contributes to climate change. Reducing methane emission in grazing livestock systems is therefore important. However, measuring methane from individual grazing animals is difficult, costly, and often impractical under commercial conditions. The rumen microbiome has been used as a proxy for estimating methane emissions, but collecting rumen samples is invasive and impractical for large-scale use. Because rumination transfers material from the rumen to the mouth, we investigated whether microbes found in cattle mouths could also be used to explain variations in methane production among individual animals. We suggest that mouth-swab sampling method can be an alternative to rumen fluid sampling because it was less invasive, relatively quick and practically applicable in commercial conditions. Importantly, the microbiome explained a meaningful proportion of the between-animal variation for methane emission. This suggests that collection of mouth swabs is a potentially scalable alternative proxy method that can be further tested in a larger cohort for its predictive accuracy in informing methane production by accounting for additional factors that could influence methane emissions, such as feed intake and host genetic. Overall, our findings support the potential use of oral ruminant microbial information to estimate methane production in extensive and commercial-scale farming systems.

The rapid rise in inflammatory bowel disease (IBD) worldwide parallels urbanization and Westernization, including a shift towards the Western diet. This evolving epidemiological landscape shines a spotlight on the contributions of the environment to IBD pathogenesis and has generated particular interest in the role of diet as both a therapeutic and preventative strategy. Although epidemiologic studies have identified dietary risk associations and dietary intervention studies have demonstrated symptomatic benefit, the specific dietary components that influence disease course and the complex mechanistic pathways through which they act are incompletely understood. In this narrative review, we examine the clinical efficacy of dietary therapies studied in IBD and discuss their effects on gut microbial composition and function, recognizing the heterogeneity of evidence across dietary approaches and the evolving nature of this field. We also discuss emerging evidence linking diet, microbial metabolism and immune response, and consider how a better understanding of these interactions may inform future therapeutic strategies, optimize dietary interventions, and support the development of precision nutrition approaches in IBD. Overall, current evidence suggests that dietary therapies may benefit selected patients with IBD and are associated with changes in the gut microbiome, although their mechanisms and optimal clinical application require further study.

Introductory biology instructors contend with the tension between the inherent complexity of the discipline and cognitively overloading their students. While oversimplification may promote misconceptions, without sufficient simplification, students may fail to grasp a basic understanding of disciplinary concepts. In genetics education, evidence is mounting that the risks associated with oversimplifying far outweigh the benefits, as emphasizing Mendelian principles while neglecting the role of environment not only fails to reflect our current understanding of genes and genomes but can also inadvertently reinforce the misinformed belief that genes alone determine people's physical, cognitive, and behavioral characteristics. Examples and activities featuring human pedigrees can be particularly insidious. While excellent tools for helping students apply fundamental genetics concepts and practice analytical skills, they reduce phenotypic variation to a dichotomous "affected" vs. "unaffected" model with perfectly Mendelian inheritance and the underlying, unspoken assumption that phenotype is entirely determined by genotype. There is a need for instructional resources that present genetics in a way that better reflects present-day knowledge, make light of the complexities hidden behind pedigree charts, and allow students to appreciate the multifactorial nature of phenotypic variation, and the challenges of classifying individuals into discrete categories. To help fill this gap, we offer an engaging lesson that promotes critical pedigree analysis skills and honors the complexities of phenotypic variation.

In this exploratory pilot study, quantitative analyses were performed on seven leather wheelchairs and the protective barrier was evaluated on three leather wheelchairs, while shotgun metagenomic sequencing (Illumina and Oxford Nanopore) was conducted on pooled samples obtained from seven leather and three fabric wheelchairs to characterize microbial DNA recovered from wheelchair surfaces under routine clinical conditions. Microbial DNA and biomass were detected on all sampled surfaces, with median DNA concentrations of approximately 0.015 ng/µL, median cell counts of approximately 4.8 × 105 cells/mL, and median OD600 values of approximately 0.038, although variability among wheelchairs was observed. NGS analysis revealed heterogeneous microbial communities composed mainly of taxa associated with human skin microbiota and environmental sources. Opportunistic taxa including Escherichia coli, Staphylococcus haemolyticus, Achromobacter xylosoxidans, and Clostridioides difficile DNA were detected. Differences in microbial composition were observed between the pooled fabric and leather samples, with fabric samples characterized by the dominance of specific taxa and leather samples exhibiting a more heterogeneous microbial profile. In addition, median DNA concentration, cell counts, and OD600 values were reduced by approximately 98-100% on the protective barrier compared with uncovered wheelchair surfaces, with statistically significant differences between conditions. Overall, these findings suggest that hospital wheelchairs may harbor measurable levels of microbial biomass and microbial DNA despite routine sanitation procedures. Lower contamination levels were observed on the protective barrier under the conditions tested. Due to the exploratory nature of the study, the small sample size, and the use of pooled samples for metagenomic analyses, these observations should be interpreted with caution and require confirmation in larger studies.

Intratumoral microbiota, an important component of the tumor microenvironment (TME), have attracted increasing attention in cancer immunotherapy. Emerging evidence links intratumoral microbiota to tumor immune microenvironment (TIME) remodeling, immune cell infiltration, and heterogeneous responses to immune checkpoint inhibitors (ICIs). However, the overall research landscape, knowledge base, and hotspot evolution in this field remain insufficiently characterized. This study aimed to systematically map this field through bibliometric and visualization analyses. Publications up to November 8, 2025, were retrieved from the Web of Science Core Collection, Scopus, and PubMed. After screening, deduplication, and data standardization, bibliometric analyses were performed using R, VOSviewer, CiteSpace, and Scimago Graphica to examine publication trends, collaboration networks, knowledge bases, and keyword evolution. A total of 245 publications were included, comprising 141 original articles and 104 reviews. Since the first publication appeared in 2017, the field has grown exponentially, with a compound annual growth rate (CAGR) of 63.1% from 2017 to 2024. China ranked first in publication output, followed by the United States, while the United States occupied a more central position in total citations and international collaboration. Frontiers in Immunology was the most productive journal, whereas Science, Cell, and Nature constituted the major co-cited knowledge base, with 1,172, 729, and 670 co-citations, respectively. Keyword analysis showed that "intratumoral microbiota" was the most frequent term (90 occurrences), with excellent clustering quality (modularity Q = 0.6963; silhouette S = 0.9351). Research hotspots have gradually shifted from early explorations of gut microbiota, CD8+ T cells, and immune mechanisms toward immunotherapy resistance, microbial biomarkers, and microbiota-targeted interventions, including engineered bacteria, extracellular vesicles, and fecal microbiota transplantation. Research on intratumoral microbiota in cancer immunotherapy has rapidly developed into a distinct interdisciplinary field. Current hotspots are moving from mechanistic exploration toward response prediction and translational intervention. Future studies should prioritize standardized detection, spatial and multi-omics validation, and multicenter prospective evaluation to support the clinical translation of microbiota-based biomarkers and therapeutic strategies.

Due to widespread availability and familiarity, unfractionated heparin (UFH) is the most used intravenous anticoagulant for many indications in hospitalised patients. UFH, however, is a high-risk medication with complex pharmacokinetics and pharmacodynamics that are highly variable between different patients and within the same patients over time. The traditional titration and monitoring approach uses a clot-based assay, the activated partial thromboplastin time (aPTT), titrated to one and a half to two and a half times the upper limit of the normal range. Alternate assays indirectly measuring the anti-Xa level have not been compared with the aPTT for the monitoring of heparin in a prospective study. The optimal laboratory test for monitoring and adjusting heparin is not known. Our pragmatic study developed within the learning healthcare infrastructure is designed to answer this clinical question by comparing two established protocols for monitoring heparin in our hospital through a pragmatic randomised clinical trial. The Comparison of Heparin Assay Monitoring Protocols (CHAMP) Trial is a single-centre, pragmatic, randomised trial conducted at Vanderbilt University Medical Centre (VUMC) beginning 26 June 2024. The CHAMP trial compares the aPTT protocol to the anti-Xa protocol for monitoring and titration of intravenous UFH for systemic anticoagulation in hospitalised adult patients. Admitted patients initiated on UFH protocols are assigned to either the aPTT or anti-Xa protocol in a randomised fashion. The primary outcome is time to reach the therapeutic anticoagulation range by coagulation assay. Secondary outcomes include the percent of measurements in the therapeutic range, the number of coagulation laboratory measurements over time, frequency of heparin rate changes while on the protocol and the incidence of thrombotic and clinically relevant bleeding events. The CHAMP trial is an ongoing pragmatic trial embedded into the current existing clinical workflow for heparin administration. The two protocols are considered clinically equivalent and already used in clinical practice, allowing for a waiver of consent approval (VUMC Institutional Review Board #232192). This waiver is critical to the implementation of the study due to the nature of scenarios and time constraints in which UFH is typically initiated. Partnering with nursing, pharmacy and clinical providers has been key to launching this study, which provides the first prospective, randomised, direct comparison of the two heparin laboratory protocols available for the monitoring and titration of intravenous UFH in hospitalised patients. After trial completion and data analysis, the findings of the CHAMP trial will be submitted to a peer-reviewed journal for consideration of publication for distribution to a broad clinical audience. The CHAMP study was registered on ClinicalTrials.gov (NCT identifier: NCT06329921) on 19 March 2024. The first patient was enrolled in the study on 26 June 2024, with enrolment of the planned 700 participants expected to occur over two years.

Neonatal bacterial infections, specifically bacteremia, have been attributed to microorganisms acquired in the perinatal period. Earlyonset neonatal sepsis is commonly caused by organisms, predominantly bacteria, acquired during delivery or immediately after birth. Bacterial etiological agents of early and lateonset neonatal bacteremia are: Escherichia coli, Group B Streptococci, Listeria monocytogenes, Staphylococcus aureus, enterococci, coagulasenegative Staphylococcus, and other Enterobacterales. Organisms causing neonatal bacteremia reported across the world are scarce, often associated with deviceassociated infection and environmental contamination. We present a case of lateonset neonatal sepsis in a 6dayold baby caused by Vibrio cholerae, which is a very rare and not reported from most parts of the world. The unusual nature of this infection linked to source identification makes this report exclusively the first from Oman.

Methane (CH4) from ruminants is a major source of agricultural greenhouse gas and represents a loss of dietary energy. 3-nitrooxypropanol (3-NOP) is a known methanogenesis inhibitor, but its hydrophilic nature may limit the cellular accessibility to methanogens. Here, we systematically evaluated 1,3-propanediol dinitrate (1,3-PDN), a more hydrophobic derivative of 3-NOP, for its anti-methanogenic potential and underlying mode of action using ruminal fermentation, pure-culture assays, multi-omics analyses, and molecular docking. Intracellular accumulation assays indicated greater cellular accumulation of 1,3-PDN than 3-NOP in rumen-derived methanogen Methanobrevibacter olleyae. Ruminal fermentation assays showed that 1,3-PDN reduced CH4 production by ~55%, and altered hydrogen (H2) metabolism, leading to 11-fold increase in H2 accumulation. Metatranscriptomic profiling revealed that 1,3-PDN significantly altered the active archaeal community, with a notable reduction in Methanobrevibacter_A and suppression of hydrogenotrophic methanogenesis. Molecular docking suggested that 1,3-PDN may bind to the conserved active site of methyl-coenzyme M reductase (MCR), potentially contributing to MCR-associated inhibition. Proteomic analysis further indicated that 1,3-PDN supplementation downregulated key MCR subunits and simultaneously affected other redox-sensitive methanogenesis-related processes, including tetrahydromethanopterin S-methyltransferase (MTR) subunits and proteins involved in the biosynthesis of cofactors F430 and cobalamin. Nitrogen-equivalent assay suggested partial contribution of nitrite to the methanogenesis inhibition and oxidative effects induced by 1,3-PDN. Together, these findings identify 1,3-PDN as an effective inhibitor of ruminal methanogenesis with enhanced cellular enrichment, providing mechanistic insights for the rational development of new CH4 inhibitors.

Methicillin-resistant Staphylococcus aureus (MRSA) pose a formidable health threat owing to their multidrug resistance (MDR) nature, robust biofilms and persistence. Natural product-based medications are a highly viable strategy for challenging MDR and biofilm persistence with diverse therapeutic benefits. In this study, the triterpenoid Astrakurkurone, previously purified from a wild edible mushroom Astraeus hygrometricus, showed antibacterial efficacy against MRSA BAA1717 and a clinical isolate (MRSA CI-1) with MICs ranging from 150 to 300 μg/mL. 1/2 MIC concentration of Astrakurkurone also inhibited 93.95% and 88.31% of MRSA BAA1717 and MRSA CI-1 biofilms through downregulating quorum sensing and virulence factors such as agrA, sarA, bap, sasG, icaA, and hla. The inhibition of staphyloxanthin production by Astrakurkurone was another interesting insight, sensitizing bacterial cells to reactive oxygen species (ROS). The accumulation of ROS was observed as one of the primary mechanisms of Astrakurkurone that affected potential and integrity of cell membrane. Intriguingly, Astrakurkurone acted as a β-lactamase inhibitor by downregulating blaZ expression by ∼11.11 fold. Moreover, a synergistic and additive interaction of Astrakurkurone with β-lactam antibiotic cefoxitin was evinced, supporting its β-lactamase inhibitory nature. Furthermore, the antibiotic-induced and biofilm-induced persister cells were eliminated by Astrakurkurone, providing another important insight for recurrent and chronic disease management. Astrakurkurone eradicated matured biofilms from urinary catheter, goat skin wound, skin burn wound and lung sections, strengthening applicability potential. In summary, the antibiofilm, antivirulence and antipersister nature of Astrakurkurone could emerge as a promising therapeutic alternative for the cure of medicinal implant-associated maladies, severe skin and lung infections with enhanced efficacy.

Nature-based wastewater treatment systems are increasingly implemented to support water reuse in arid regions, yet their effectiveness in removing viable culturable opportunistic pathogens remains insufficiently characterized. In this exploratory, culture-based study, we assessed bacterial population dynamics across a five-stage natural wastewater treatment system (Wadi Hanifa, Riyadh, Saudi Arabia), tracking culturable bacteria from secondary-treated influent to sand-filtered effluent. Water samples were collected at five sequential treatment stages and analyzed for physicochemical parameters, total culturable bacterial abundance, bacterial diversity, taxonomic composition, and antimicrobial susceptibility of persistent isolates. Total culturable bacterial counts decreased by approximately 1.1 log10 CFU mL‒1 across the system, accompanied by an approximately 50% reduction in observed isolate richness. The fecal indicator Escherichia coli was detected only in upstream and intermediate stages (sampling locations L3.1-L3.3) and was absent from downstream samples. In contrast, the opportunistic pathogen Klebsiella pneumoniae was recovered across all five treatment stages and accounted for 44.4% (8/18) of all morphologically distinct isolates grown on the selected culture media. Turbidity declined by 71% along the treatment train and showed a strong positive correlation with bacterial richness (Kendall's τ = 0.84, p = 0.038), although this exploratory correlation should be interpreted with caution given the small sample size (n = 5 stages). Phenotypic antimicrobial susceptibility testing revealed multidrug resistance (MDR) in 62.5% (5/8) of K. pneumoniae isolates, although all remained susceptible to amikacin and meropenem. Under the conditions examined, multi-stage natural wastewater treatment substantially reduced overall bacterial abundance and diversity but did not eliminate viable, multidrug-resistant Klebsiella pneumoniae. The discordance between fecal-indicator removal and opportunistic pathogen recovery highlights system-specific limitations of indicator-based monitoring for assessing microbial safety in wastewater reuse systems. Given the limited isolate number (n = 8 K. pneumoniae) and the absence of molecular resistance-gene characterization, broader claims about wastewater as a dissemination pathway for antimicrobial resistance cannot be drawn from these data. These findings are based on a single cross-sectional sampling event and should be considered hypothesis-generating rather than confirmatory.

Hookworm infection remains a major public health concern, particularly in tropical regions such as Southeast Asia (SEA), where environmental and socio-economic conditions favour transmission. Despite the substantial burden, current knowledge of hookworm epidemiology in SEA remains fragmented as limited efforts have been made to synthesis findings across human and small animal populations. This systematic review aimed to summarize existing literature from January 1, 2015 through March 7, 2025 on the prevalence and risk factors of hookworm infection in both human and small animal populations across SEA. Pooled hookworm prevalence was 9.1% (95% CI: 6.6%-12.3%) among 10 2064 humans and 34.3% (95% CI: 21.6%-49.8%) among 4 219 small animals. In humans, the most prevalent combination was hookworm, Trichuris spp., and Ascaris spp. (15.6%, 95% CI:14.7%-16.5%), followed by hookworm and Strongyloides spp. (14.0%, 95% CI: 13.2%-14.8%). Animal hookworm coinfection was frequently associated with Toxocara spp. (57.7%, 95% CI: 52.4%-62.9%). These findings highlight the complex nature of hookworm transmission in SEA, imply the need for integrated One Health based control strategies. Future research is recommended to focus on urban settings and investigate host-parasites interactions underlying coinfections to support the development of more effective and context specific intervention strategies.

Severe Plasmodium falciparum malaria is a potentially fatal illness associated with diverse systemic and neurological manifestations. While cerebral malaria is a wellrecognized complication, hemorrhagic stroke remains an exceptionally uncommon presentation. We report a rare case of severe malaria complicated by an acute left intracerebral hematoma, resulting in right-sided hemiparesis with facial nerve palsy. This report adds to the limited existing literature on malaria-associated hemorrhagic stroke and underscores its neurovascular implications. A 16-year-old female presented with a 6-day history of high-grade fever with chills, jaundice, and a 2-day history of altered sensorium. On admission, her Glasgow Coma Scale (GCS) score was E2V3M4, with splenomegaly and bilateral lung crepitations. Investigations revealed severe thrombocytopenia, hepatic dysfunction, hemolysis on peripheral smear, and Plasmodium falciparum parasitemia. Chest radiography showed bilateral perihilar opacities. She was treated with artemisinin-based combination therapy, doxycycline, and supportive care, with her GCS improving to 14. On day 10, she developed seizures and right-sided hemiparesis with right upper motor neuron (UMN) facial nerve palsy. Computed tomography of the brain demonstrated a left acute intracerebral hematoma. A diagnosis of severe P. falciparum malaria with multiorgan involvement and post-malaria neurological syndrome complicated by hemorrhagic stroke was made. The clinical course was notable for severe thrombocytopenia and a delayed onset of intracerebral hemorrhage during the recovery phase, underscoring the evolving and dynamic nature of neurological complications in severe malaria. With rehabilitation, she achieved complete neurological recovery at 3 months. This case highlights a possible association between severe malaria and hemorrhagic stroke, with proposed mechanisms including microvascular sequestration, coagulopathy, thrombocytopenia, and endothelial dysfunction. Prompt recognition, early neuroimaging, and a multidisciplinary management approach are essential to improve outcomes in these complex neurovascular presentations.

Currently, respiratory drug-resistant bacterial infections are a major global public health challenge due to their protracted course of disease and suboptimal treatment outcomes. In the face of slow progress in the development of new antibiotics, TCM offers novel perspectives for preventing and treating such infections by leveraging its unique advantages in holistic regulation and syndrome differentiation. This paper, for the first time, systematically constructed a TCM composite pathogenesis model centered on the core concept of bacteria-toxin-stasis-deficiency. It elucidated the dynamic evolution pattern characterized by deficiency in nature and excess in superficiality and proposed a stage-specific and syndrome-specific diagnostic and therapeutic framework, along with a prevention and treatment strategy of advancing intervention to intercept and reverse disease progression. From a TCM perspective, these infections can be categorized under conditions such as wind-warmth, lung abscess, cough, or latent pathogen. The key pathogenesis involves "internal deficiency of lung Qi leading to lingering pathogenic factors", resulting in the mutual binding of phlegm, stasis, and toxins in the lungs. Based on the dynamic interplay between healthy Qi and pathogenic factors, the clinical presentation can be divided into two phases: pathogen excess with healthy Qi impairment and healthy Qi deficiency with lingering pathogen. These phases encompass core syndrome types including healthy Qi deficiency with lingering pathogen, latent pathogen in pleurodiaphragmatic interspace, phlegm-stasis-toxin binding, and dual deficiency of Qi and Yin. Therapeutically, modified classical formulas such as Maxing Shigan Decoction, Zhuye Shigao Decoction, Dayuanyin, Qianjin Weijing Decoction, and Shashen Maidong Decoction are employed to embody the principle of reinforcing healthy Qi and eliminating pathogen. Clinical practice demonstrates that adhering to an integrated traditional Chinese and western medicine model guided by the principles of integrating pathogenesis with pathology and medicinal properties with pharmacology can effectively improve patient prognosis, reduce recurrence rates, and enhance quality of life. This approach provides a new paradigm of integrated traditional Chinese and western medicine for addressing the global crisis of antimicrobial resistance.

Forest litter, formed from the metabolic by-products of plant growth, plays a key role in nutrient cycling and microbial community dynamics within forest ecosystems. This study investigated the characteristics of organic acid production during leaf litter decomposition and its influence on bacterial diversity over a 90-day decomposition period at room temperature (25&#x2009;&#xb1;&#x2009;2 &#x2103;). Samples of leaf litter derived from the fallen leaves of Myrica ruba, Bambusa cerosissima, and Pinus sylvestris in Daluo Mountain (Wenzhou) and Machilus thunbergii, Cunninghamia lanceolata, and Quercus acutissima in Wuyanling National Nature Reserve (Zhejiang) were collected and subjected to decomposition, and the resulting organic acid profiles and bacterial diversity were analyzed. The results showed that organic acid levels increased significantly during the early stages of decomposition, peaking before gradually declining over a 90-day period. Bacterial diversity was consistently higher on the leaf interior compared to the surface. Among the species studied, Bambusa cerosissima and Cunninghamia lanceolata supported greater bacterial diversity than Machilus thunbergii and Quercus acutissima. Bacterial abundance increased during early decomposition, reaching its highest point at day 50, before decreasing. Proteobacteria and Sphingomonas were identified as the dominant bacterial groups throughout decomposition. The heatmap of inter&#x2011;group correlation analysis revealed that there were highly significant relationships (p&#x2009;<&#x2009;0.01) between fumaric acid and Proteobacteria at the phylum level, both on leaf surfaces and internally. At the genus level, oxalic, lactic, fumaric, malic, and citric acids showed significant differences with dominant bacteria. These findings highlight the important role of organic acid production and microbial diversity in leaf litter during decomposition, offering new insights into their combined impact on forest ecosystem function and nutrient cycling.

Helicobacter pylori remains a primary driver of chronic gastritis, peptic ulcers, and stomach cancer. However, surging antimicrobial resistance now causes treatment to fail in a significant number of patients. Because of their multi-target bactericidal processes, silver nanoparticles (AgNPs) have become a viable alternative antimicrobial therapy. In the current research, AgNPs were greenly synthesized employing Aspergillus niger AH1 (A. niger AH1) through an ecofriendly method. The biosynthesized AgNPs showed a characteristic surface plasmon resonance (SPR) peak at 420&#xa0;nm, validating successful nanoparticles (NPs) development. Transmission electron microscope (TEM) analysis discovered primarily spherical and well-dispersed NPs with a size range of 8-38&#xa0;nm, while dynamic light scattering (DLS) analysis exhibited an average hydrodynamic diameter of approximately 40&#xa0;nm and a low polydispersity index (PDI&#x2009;=&#x2009;0.122), indicating high colloidal stability. Furthermore, the X-ray diffraction (XRD) analysis illustrated the crystalline nature of the obtained AgNPs with characteristic face-centered cubic (FCC) diffraction peaks and 38.3&#xa0;nm average crystallite size. The biosafety of the biosynthesized AgNPs was assessed toward normal cell lines; results revealed that the biosynthesized AgNPs are safe in use, where the IC50 was 306.4 and 336.9&#xa0;&#xb5;g/ml toward Wi-38 and Vero cell lines, respectively. The destructive ability of AgNPs against 17 clinical H. pylori isolates was thoroughly assessed using different microbiological assays. The minimum inhibitory concentration (MIC) values varied from 64 to 256&#xa0;&#xb5;g/mL, while minimum bactericidal concentration (MBC) values ranged from 64 to 1024&#xa0;&#xb5;g/mL. All isolates had MIC/MBC ratios of &#x2264;&#x2009;4, indicating the bactericidal mode of action of AgNPs. In addition, AgNPs exhibited dose-dependent biofilm inhibition at sub-MIC concentrations, ranging from 1.31 to 60.42%. Mechanistic studies were subsequently performed using Hp13, the most susceptible isolate. In this representative isolate, AgNPs combined with amoxicillin and clarithromycin showed synergistic interactions in the checkerboard assay. AgNPs also suppressed urease activity in a concentration-dependent manner (IC&#x2085;&#x2080; = 7.05&#xa0;&#xb5;g/mL), a concentration well below the isolate's MIC. Time-kill kinetics confirmed rapid bactericidal activity, while increased protein leakage indicated membrane disruption. These findings demonstrate that AgNPs possess potent antibacterial activity against clinical H. pylori isolates, whereas the mechanistic evidence was obtained using the representative isolate Hp13.