Monitoring Gene Sequences of Staphylococcus aureus Using a Love-Mode Surface Acoustic Wave Biosensor Coated with Cellulose Acetate/Polyethylenimine Nanofibers and Au Nanoparticles.

Love-mode surface acoustic wave (SAW) sensors show great promise for biodetection applications owing to their low cost, digital output, and wireless passive capability, but their performance is often restricted by the availability of suitable sensitive membrane layers. Herein, a composite layer of electrospun fibers made from cellulose acetate and polyethylenimine, coated with gold nanoparticles, is proposed as a porous and sensitive membrane coated onto a love-mode SAW biosensor for monitoring gene sequences of Staphylococcus aureus. The results showed that the developed sensor exhibited an impressive sensitivity of 122.56 Hz/(nmol/L) for detecting gene sequences of S. aureus, surpassing the sensitivity of conventional SAW sensors employing a bare Au film as the sensitive layer by 5-fold. The analysis revealed a remarkably linear detection (R2 of 0.97827) of S. aureus gene sequences within the range of 0 to 100 nmol/L. The limit of detection was impressively low at 0.9116 nmol/L. The good stability and specificity of the biosensor in liquid environments were demonstrated for clinical diagnostics.

Bulky Phosphazenium Salt Controlling Chemoselective Terpolymerization of Epoxide, Anhydride and CO2: From Well-Defined Block to Truly Random Copolymers.

Copolymers with precise compositions and controlled sequences are great appealing for high-performance polymeric materials, but their synthesis is very challenging. In this study, tetrakis[tris(dimethylamino)phosphoranylidenamino] phosphonium chloride (P5Cl) and triethylboron (TEB) were chosen as the binary catalyst to synthesize both well-defined block and truly random poly(ester-carbonate) copolymers via the one-pot/one-step terpolymerization of epoxide/anhydride/CO2 under metal-free conditions. The bulky nature of phosphazenium cation not only led to loose cation-anion pairs and enhanced the reactivity, but also provided the chain-end an appropriate protection and improved the controllability. In particular, P5Cl/TEB with a molar ratio of 1/0.5 showed an extraordinary chemoselectivity for ring-opening alternating copolymerization (ROAC) of cyclohexene oxide (CHO) and phthalic anhydride (PA) first and then ROAC of CHO/CO2. Thus, well-defined block polyester-polycarbonate copolymers were synthesized by CHO/PA/CO2 terpolymerization. The chemoselectivity was easily tuned and the ROAC of CHO/PA and ROAC of CHO/CO2 occurred simultaneously with P5Cl/TEB = 1/2, producing truly random poly(ester-carbonate) copolymers from CHO/PA/CO2. In addition, this P5Cl/TEB catalyst and the strategy to regulate its chemoselectivity are versatile for various anhydrides, epoxides and initiators. Thus, poly(ester-carbonate) copolymers with varying sequences, compositions, and topologies are successfully synthesized, making it possible to compare their properties and to expand their applications.

Bifunctional and recyclable polyesters by chemoselective ring-opening polymerization of a δ-lactone derived from CO2 and butadiene.

When aiming at the direct use of CO2 for the preparation of advanced/value-added materials, the synthesis of CO2/olefin copolymers is very appealing but challenging. The δ-lactone 3-ethylidene-6-vinyltetrahydro-2H-pyran-2-one (EVP), synthesized by telomerization of CO2 with 1,3-butadiene, is a promising monomer. However, its chemoselective ring-opening polymerization (ROP) is hampered by unfavorable thermodynamics and the competitive polymerization of highly reactive C=C double bonds under usual conditions. Herein, we report the chemoselective ROP of EVP using a phosphazene/urea binary catalyst, affording exclusively a linear unsaturated polyester poly(EVP)ROP, with a molar mass (Mn) up to 16.1 kg·mol-1 and a narrow distribution (Ð < 1.6), which can be fully recycled back to the pristine monomer, thus establishing a monomer-polymer-monomer closed-loop life cycle. In these polyesters, the CO2 content reaches 33 mol% (29 wt%). The reasons for the unexpected chemoselectivity were investigated by Density-functional theory (DFT) calculations. The poly(EVP)ROP features two pendent C=C double bonds per repeating unit, which show distinct reactivity and thus can be properly engaged in sequential functionalizations towards the synthesis of bifunctional polyesters. We disclose here a methodology providing a facile access to bifunctional and recyclable polyesters from readily available feedstocks.

Surface acoustic wave platform integrated with ultraviolet activated rGO-SnS2 nanocomposites to achieve ppb-level dimethyl methylphosphonate detection at room-temperature.

Dimethyl methylphosphonate (DMMP) is commonly used as an alternative for demonstrating to detect sarin, which is one of the most toxic but odorless chemical nerve agents. Among various types of DMMP sensors, those utilizing surface acoustic wave (SAW) technology provide notable advantages such as wireless/passive monitoring, digital output, and a compact, portable design. However, key challenges for SAW-based DMMP sensors operated at room temperature lies in simultaneous enhancement of sensitivities and reduction of detection limits. In this study, we developed a binary material strategy by combining reduced graphene oxide (rGO) and tin disulfide (SnS2) with (100)-facets orientation as sensing layers of SAW device for DMMP detection utilized at room temperature. Ultraviolet (UV) light was applied to activate the sensitive film and reduce the sensor's response time. The developed SAW DMMP sensor demonstrated a superior sensitivity (-1298.82 Hz/ppm), a low detection limit of 50 ppb, and a hysteresis below 1.5%, along with fast response/recovery time (39.2 s/28.4 s), excellent selectivity, long-term stability and repeatability. The formation of shrub-like rGO-SnS2 heterojunctions with abundant surface defects and large specific surface areas, high-energy (100) crystalline surfaces of SnS2, and photogenerated carriers generated by UV irradiation were pinpointed as the crucial sensing mechanisms. These factors collectively enhanced adsorption and reaction dynamics of DMMP molecules.

A Novel Approach for Real-Time Determination of 15N-Enriched Hydroxylamine.

Hydroxylamine (NH2OH) is a critical precursor of nitrous oxide (N2O) and key intermediate in the nitrogen cycle. However, the conversion of NH2OH is very fast, and the lack of real-time 15N analytical methods for NH2OH hinders the on-time capture of its biochemical signals in the N cycle. To bridge this gap, we developed a novel approach for real-time determination of 15N-enriched NH2OH. In this approach, an automated sample inlet unit was coupled to a membrane-inlet mass spectrometer, and NH2OH was converted to N2O by sodium hypochlorite for analysis. The interference of carbon dioxide was successfully removed by an ascarite trap, and the N2O signal showed good linearity over the targeted NH2OH concentrations. The limit of detection and limit of quantification of this approach were 0.38 and 1.28 µM, respectively, and 15N enrichment can be accurately detected when the 15N enrichment is higher than 5 atom %. This approach provides a first online analytical tool to capture real-time NH2OH transforming signals using the 15N tracing technique, which will advance mechanism studies of the N cycle.

Sodium octanoate mediates GPR84-dependent and independent protection against sepsis-induced myocardial dysfunction.

INTRODUCTION: This study aims to evaluate the therapeutic effects of sodium octanoate (SO), a medium-chain fatty acid salt, on SIMD in a murine model and to explore its underlying mechanisms. METHODS: Male mice were subjected to sepsis models through two methods: intraperitoneal injection of lipopolysaccharide (LPS) and cecal ligation and punction (CLP). Mice received interval doses of SO every 2 hours or 4 hours for a total of six times or three times after LPS treatment. The relationship between SO and G protein-coupled receptor 84 (GPR84) was evaluated through GEO data analysis and molecular docking studies. DBA/2 mice were used to study the role of the GPR84 protein in the SO-mediated protection. Energy metabolomics was utilized to comprehensively assess the impact of SO on the levels of cardiac energy metabolic products in septic mice. histone modification identification techniques were used to further identify the specific sites of histone modification in the hearts of SO-treated septic mice. RESULTS: SO treatment significantly improved myocardial contractile function, restored the oxidative stress imbalance and enhanced the myocardium's resistance to oxidative injury. SO significantly promotes the expression of GPR84. The loss of GPR84 function markedly attenuates the protective effects of SO. SO enhanced myocardial energy metabolism by promoting the synthesis of acetyl-CoA and upregulating genes involved in fatty acid ß-oxidation which were abolished by medium-chain acyl-CoA dehydrogenase (MCAD) knockdown. SO induced histone acetylation, particularly at H3K123 and H3K80. CONCLUSION: Our study demonstrates that SO exerts protective effects against SIMD through both GPR84-mediated anti-inflammatory and antioxidant actions and GPR84-independent enhancement of myocardial energy metabolism, possibly mediated by MCAD.

A global dataset of gross nitrogen transformation rates across terrestrial ecosystems.

Rates of nitrogen transformations support quantitative descriptions and predictive understanding of the complex nitrogen cycle, but measuring these rates is expensive and not readily available to researchers. Here, we compiled a dataset of gross nitrogen transformation rates (GNTR) of mineralization, nitrification, ammonium immobilization, nitrate immobilization, and dissimilatory nitrate reduction to ammonium in terrestrial ecosystems. Data were extracted from 331 studies published from 1984-2022, covering 581 sites. Globally, 1552 observations were appended with standardized soil, vegetation, and climate data (49 variables in total) potentially contributing to the observed variations of GNTR. We used machine learning-based data imputation to fill in partially missing GNTR, which improved statistical relationships between theoretically correlated processes. The dataset is currently the most comprehensive overview of terrestrial ecosystem GNTR and serves as a global synthesis of the extent and variability of GNTR across a wide range of environmental conditions. Future research can utilize the dataset to identify measurement gaps with respect to climate, soil, and ecosystem types, delineate GNTR for certain ecoregions, and help validate process-based models.

Bioactive sphingolipids as emerging targets for signal transduction in cancer development.

Sphingolipids, crucial components of cellular membranes, play a vital role in maintaining cellular structure and signaling integrity. Disruptions in sphingolipid metabolism are increasingly implicated in cancer development. Key bioactive sphingolipids, such as ceramides, sphingosine-1-phosphate (S1P), ceramide-1-phosphate (C1P), and glycosphingolipids, profoundly impact tumor biology. They influence the behavior of tumor cells, stromal cells, and immune cells, affecting tumor aggressiveness, angiogenesis, immune modulation, and extracellular matrix remodeling. Furthermore, abnormal expression of sphingolipids and their metabolizing enzymes modulates the secretion of tumor-derived extracellular vesicles (TDEs), which are key players in creating an immunosuppressive tumor microenvironment, remodeling the extracellular matrix, and facilitating oncogenic signaling within in situ tumors and distant pre-metastatic niches (PMNs). Understanding the role of sphingolipids in the biogenesis of tumor-derived extracellular vesicles (TDEs) and their bioactive contents can pave the way for new biomarkers in cancer diagnosis and prognosis, ultimately enhancing comprehensive tumor treatment strategies.

Selective increase of antibiotic-resistant denitrifiers drives N2O production in ciprofloxacin-contaminated soils.

Agricultural systems significantly contribute to global N2O emissions, which is intensified by excessive fertilization and antibiotic residues, attracting global concerns. However, the dynamics and pathways of antibiotics-induced soil N2O production coupled with microbial metabolism remain controversial. Here, we explored the pathways of N2O production in agricultural soils exposed to ciprofloxacin (CIP), and revealed the underlying mechanisms of CIP degradation and the associated microbial metabolisms using 15N-isotope labeling and molecular techniques. CIP exposure significantly increases the total soil N2O production rate. This is attributed to an unexpected shift from heterotrophic and autotrophic nitrification to denitrification and an increased abundance of denitrifiers Methylobacillus members under CIP exposure. The most striking strain M. flagellatus KT is further discovered to harbor N2O-producing genes but lacks a N2O-reducing gene, thereby stimulating denitrification-based N2O production. Moreover, this denitrifying strain is probably capable of utilizing the byproducts of CIP as carbon sources, evidenced by genes associated with CIP resistance and degradation. Molecular docking further shows that CIP is well ordered in the catalytic active site of CotA laccase, thus affirming the potential for this strain to degrade CIP. These findings advance the mechanistic insights into N2O production within terrestrial ecosystems coupled with the organic contaminants degradation.

Signature Search Polestar: a comprehensive drug repurposing method evaluation assistant for customized oncogenic signature.

SUMMARY: The burgeoning high-throughput technologies have led to a significant surge in the scale of pharmacotranscriptomic datasets, especially for oncology. Signature search methods (SSMs), utilizing oncogenic signatures formed by differentially expressed genes through sequencing, have been instrumental in anti-cancer drug screening and identifying mechanisms of action without relying on prior knowledge. However, various studies have found that different SSMs exhibit varying performance across pharmacotranscriptomic datasets. In addition, the size of the oncogenic signature can also significantly impact the result of drug repurposing. Therefore, finding the optimal SSMs and customized oncogenic signature for a specific disease remains a challenge. To address this, we introduce Signature Search Polestar (SSP), a webserver integrating the largest pharmacotranscriptomic datasets of anti-cancer drugs from LINCS L1000 with five state-of-the-art SSMs (XSum, CMap, GSEA, ZhangScore, XCos). SSP provides three main modules: Benchmark, Robustness, and Application. Benchmark uses two indices, Area Under the Curve and Enrichment Score, based on drug annotations to evaluate SSMs at different oncogenic signature sizes. Robustness, applicable when drug annotations are insufficient, uses a performance score based on drug self-retrieval for evaluation. Application provides three screening strategies, single method, SS_all, and SS_cross, allowing users to freely utilize optimal SSMs with tailored oncogenic signature for drug repurposing. AVAILABILITY AND IMPLEMENTATION: SSP is free at https://web.biotcm.net/SSP/. The current version of SSP is archived in https://doi.org/10.6084/m9.figshare.26524741.v1, allowing users to directly use or customize their own SSP webserver.

Association between frailty and hypoproteinaemia in older patients: meta-analysis and systematic review.

OBJECTIVE: Frailty and hypoproteinaemia are common in older individuals. Although there is evidence of a correlation between frailty and hypoproteinaemia, the relationship between frailty and hypoproteinaemia in hospitalized/critically ill and older community residents has not been clarified. Therefore, the aim of our meta-analysis was to evaluate the associations between frailty and hypoproteinaemia in different types of patients. METHODS: A systematic retrieval of articles published in the PubMed, Embase, Medline, Web of Science, Cochrane, Wanfang, and CNKI databases from their establishment to April 2024 was performed to search for studies on the associations between severity of frailty or prefrailty and hypoproteinaemia in older adults. The Newcastle‒Ottawa Scale and the Agency for Healthcare Research and Quality Scale were used to assess study quality. RESULTS: Twenty-two studies were included including 90,351 frail older people were included. Meta-analysis revealed an association between frailty or prefrailty and hypoproteinaemia (OR = 2.37, 95% CI: 1.47, 3.83; OR = 1.62, 95% CI: 1.23, 2.15), there was no significant difference in the risk of hypoproteinaemia between patients with severe frailty and those with low or moderate frailty (OR = 0.62, 95% CI:0.44, 0.87). The effect of frailty on the occurrence of hypoproteinaemia was more obvious in hospitalized patients/critically ill patients than in surgical patients (OR = 3.75, 95% CI: 2.36, 5.96), followed by older community residents (OR = 2.30, 95% CI: 1.18, 4.49). CONCLUSION: Frailty is associated with hypoproteinaemia in surgical patients, hospitalized older patients and older community residents. Future studies should focus on the benefits of albumin supplementation in preventing or alleviating frailty and related outcomes in the future.

Enhancing soil gross nitrogen transformation through regulation of microbial nitrogen-cycling genes by biodegradable microplastics.

Microplastics (MPs) in agricultural plastic film mulching system changes microbial functions and nutrient dynamics in soils. However, how biodegradable MPs impact the soil gross nitrogen (N) transformations and crop N uptake remain significantly unknown. In this study, we conducted a paired labeling 15N tracer experiment and microbial N-cycling gene analysis to investigate the dynamics and mechanisms of soil gross N transformation processes in soils amended with conventional (polyethylene, PE) and biodegradable (polybutylene adipate co-terephthalate, PBAT) MPs at concentrations of 0 %, 0.5 %, and 2 % (w/w). The biodegradable MPs-amended soils showed higher gross N mineralization rates (0.5-16 times) and plant N uptake rates (16-32 %) than soils without MPs (CK) and with conventional MPs. The MPs (both PE and PBAT) with high concentration (2 %) increased gross N mineralization rates compared to low concentration (0.5 %). Compare to CK, MPs decreased the soil gross nitrification rates, except for PBAT with 2 % concentration; while PE with 0.5 % concentration and PBAT with 2 % concentration increased but PBAT with 0.5 % concentration decreased the gross N immobilization rates significantly. The results indicated that there were both a concentration effect and a material effect of MPs on soil gross N transformations. Biodegradable MPs increased N-cycling gene abundance by 60-103 %; while there was no difference in the abundance of total N-cycling genes between soils without MPs and with conventional MPs. In summary, biodegradable MPs increased N cycling gene abundance by providing enriched nutrient substrates and enhancing microbial biomass, thereby promoting gross N transformation processes and maize N uptake in short-term. These findings provide insights into the potential consequences associated with the exposure of biodegradable MPs, particularly their impact on soil N cycling processes.

Nutrient responses of vascular plants to N2-fixing tree Alnus hirsuta encroachment in a boreal peatland.

The N2-fixing trees Alnus spp. have been widely encroaching into boreal peatlands, but the nutrient responses of native vascular plants remain unclear. Here, we compared nutrient concentrations and isotope signal of six common plants (Betula fruticosa, Salix rosmarinifolia, Vaccinium uliginosum, Rhododendron tomentosum, Chamaedaphne calyculata, and Eriophorum vaginatum) between Alnus hirsuta island and open peatland and assessed plant nutrient responses to A. hirsuta encroachment in boreal peatlands. Alnus hirsuta encroachment increased nitrogen (N) concentration of leaf, branch, and stem. Despite no significant interspecific difference in branch and stem, the increment magnitude of leaf N concentration varied among species, with greatest magnitude for R. tomentosum (55.1% ± 40.7%) and lowest for E. vaginatum (9.80% ± 4.40%) and B. fruticosa (18.4% ± 10.7%). Except for E. vaginatum, the significant increase in δ15N occurred for all organs of shrubs, with interspecific differences in change of leaf δ15N. According to the mass balance equation involving leaf δ15N, R. tomentosum and E. vaginatum, respectively, obtained highest (40.5% ± 19.8%) and lowest proportions (-14.0% ± 30.5%) of N from A. hirsuta. Moreover, the increment magnitudes of leaf N concentration showed a positive linear relationship with the proportion of N from A. hirsuta. In addition, A. hirsuta encroachment reduced leaf phosphorus (P) concentration of deciduous shrubs (i.e., B. fruticosa, S. rosmarinifolia, and V. uliginosum), thus increasing N:P ratio. These findings indicate that Alnus encroachment improves native plant N status and selectively intensifies P limitation of native deciduous shrubs, and highlight that the N acquisition from the symbiotic N2-fixing system regulates plant N responses in boreal peatlands.

Prodrug-inspired adenosine triphosphate-activatable celastrol-Fe(III) chelate for cancer therapy.

Celastrol (CEL), an active compound isolated from the root of Tripterygium wilfordii, exhibits broad anticancer activities. However, its poor stability, narrow therapeutic window and numerous adverse effects limit its applications in vivo. In this study, an adenosine triphosphate (ATP) activatable CEL-Fe(III) chelate was designed, synthesized, and then encapsulated with a reactive oxygen species (ROS)-responsive polymer to obtain CEL-Fe nanoparticles (CEL-Fe NPs). In normal tissues, CEL-Fe NPs maintain structural stability and exhibit reduced systemic toxicity, while at the tumor site, an ATP-ROS-rich tumor microenvironment, drug release is triggered by ROS, and antitumor potency is restored by competitive binding of ATP. This intelligent CEL delivery system improves the biosafety and bioavailability of CEL for cancer therapy. Such a CEL-metal chelate strategy not only mitigates the challenges associated with CEL but also opens avenues for the generation of CEL derivatives, thereby expanding the therapeutic potential of CEL in clinical settings.

Nitrifying niche in estuaries is expanded by the plastisphere.

The estuarine plastisphere, a novel ecological habitat in the Anthropocene, has garnered global concerns. Recent geochemical evidence has pointed out its potential role in influencing nitrogen biogeochemistry. However, the biogeochemical significance of the plastisphere and its mechanisms regulating nitrogen cycling remain elusive. Using 15N- and 13C-labelling coupled with metagenomics and metatranscriptomics, here we unveil that the plastisphere likely acts as an underappreciated nitrifying niche in estuarine ecosystems, exhibiting a 0.9 ~ 12-fold higher activity of bacteria-mediated nitrification compared to surrounding seawater and other biofilms (stone, wood and glass biofilms). The shift of active nitrifiers from O2-sensitive nitrifiers in the seawater to nitrifiers with versatile metabolisms in the plastisphere, combined with the potential interspecific cooperation of nitrifying substrate exchange observed among the plastisphere nitrifiers, collectively results in the unique nitrifying niche. Our findings highlight the plastisphere as an emerging nitrifying niche in estuarine environment, and deepen the mechanistic understanding of its contribution to marine biogeochemistry.

High-Strength, Thin, and Lightweight Solid Polymer Electrolyte for Superior All-Solid-State Sodium Metal Batteries.

The utilization of solid polymer electrolytes (SPEs) in all-solid-state sodium metal batteries has been extensively explored due to their excellent flexibility, processability adaptability to match roll-to-roll manufacturing processes, and good interfacial contact with a high-capacity Na anode; however, SPEs are still impeded by their inadequate mechanical strength, excessive thickness, and poor stability with Na anodes. Herein, a robust, thin, and cost-effective polyethylene (PE) film is employed as a skeleton for infiltrating poly(ethylene oxide)-sodium bis(trifluoromethanesulfonyl)imide (PEO/NaTFSI) to fabricate PE-PEO/NaTFSI SPE. The resulting SPE features a remarkable thickness of 25 µm, lightweight property (2.1 mg cm-2), superior mechanical strength (tensile strength = 100.3 MPa), and good flexibility. The SPE also shows an ionic conductivity of 9.4 × 10-5 S cm-1 at 60 °C and enhanced interfacial stability with a sodium metal anode. Benefiting from these advantages, the assembled Na-Na symmetric cells with PE-PEO/NaTFSI show a high critical current density (1 mA cm-2) and excellent long-term cycling stability (3000 h at 0.3 mA cm-2). The all-solid-state Na||PE-PEO/NaTFSI||Na3V2(PO4)3 coin cells exhibit a superior cycling performance, retaining 93% of the initial capacity for 190 cycles when matched with a 6 mg cm-2 cathode loading. Meanwhile, the pouch cell can work stably after abuse testing, proving its flexibility and safety. This work offers a promising strategy to simultaneously achieve thin, high-strength, and safe solid-state electrolytes for all-solid-state sodium metal batteries.

Effects of straw management and N levels on gross nitrogen transformations in fluvo-aquic soil of the North China Plain.

Straw incorporation with nitrogen (N) fertilization is crucial for enhancing soil fertility and minimizing negative environmental impacts by altering the magnitude and direction of soil N transformation processes. However, the response of soil N transformations to long-term carbon (C) and N inputs, and their primary driving factors, remain poorly understood. Thus, a 15N tracing study was conducted to investigate the effects of straw incorporation (AS) and straw removal (NS) with N levels of 0, 150 and 250 kg N ha-1 per season (N0, N150 and N250) on gross N transformation rates in the North China Plain after 6-year trial. Results indicated that at N0, AS significantly increased soil microbial immobilization of nitrate (NO3--N, INO3) and autotrophic nitrification rates (ONH4) compared to NS. With N fertilization, AS increased gross N immobilization (Itotal), ammonium-N immobilization (NH4+-N, INH4), net NH4+-N immobilization (InetNH4) and net NH4+-N absorption rates (AnetNH4). Specifically, at N150, AS significantly increased recalcitrant organic N mineralization rate (MNrec), while significantly reducing ONH4, labile organic N mineralization (MNlab), and gross N mineralization rates (Mtotal). At N250, AnetNH4, MNlab, MNrec and ONH4 under AS were significantly higher than under NS. Nitrogen application significantly increased ONH4, Itotal and INO3 under two straw management practices, and enhanced INH4 and InetNH4 under AS. Compared to N250, N150 significantly increased INH4 and InetNH4 under AS, while decreasing Mtotal. Opposite results were observed under NS. Meanwhile, NO3--N and dissolved organic carbon (DOC) were master factors controlling immobilization, total nitrogen (TN), hydrolysable NH4+-N (HNN) and stable organic N significantly affected AnetNH4, while labile organic N were the key environmental factors affecting MNrec, all of which positively influenced the rates of assimilation, mineralization and clay mineral adsorption. Overall, this study provides new insights into reducing N fertilization under straw incorporation by quantifying soil N transformation processes.

Integrated immunogenomic analysis of single-cell and bulk profiling reveals novel tumor antigens and subtype-specific therapeutic agents in lung adenocarcinoma.

Background: In recent years, mRNA-based vaccines with promising safety and functional characteristics have gained significant momentum in cancer immunotherapy. However, stable immunological molecular subtypes of lung adenocarcinoma (LUAD) and novel tumor antigens for LUAD mRNA vaccine development remain elusive. Therefore, a novel approach is urgently needed to identify suitable LUAD subtypes and potential tumor antigens. Methods: The Cancer Genome Atlas (TCGA), the Genotype Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases were utilized to retrieve gene expression data. The LUAD Immunological Multi-Omics Classification (LIMOC) system was developed using seven machine learning (ML) algorithms by performing integrative immunogenomic analysis of single-cell and bulk tissue transcriptome profiling. Subsequently, a panel of approaches was applied to identify novel tumor antigens. Results: First, the LIMOC system was construct to identify three subtypes: LIMOC1, LIMOC2, and LIMOC3. Second, we identified CHIT1, LILRA4, and MEP1A as novel tumor antigens in LUAD; these genes were up-regulated, amplified, and mutated, and showed a positive association with APC infiltration, making them promising candidates for designing mRNA vaccines. Notably, the LIMOC2 subtype had the worst prognosis and could benefit most from mRNA immunization. Furthermore, we performed a comprehensive in silico screening of approximately 2000 compounds and identified Sorafenib and Azacitidine as potential subtype-specific therapeutic agents. Conclusions: Overall, our study established a robust LIMOC system and identified CHIT1, LILRA4, and MEP1A as promising tumor antigen candidates for development of anti-LUAD mRNA vaccines, particularly for the LIMOC2 subtype.

Ventilator-Associated Pneumonia Prediction Models Based on AI: Scoping Review.

Background: Ventilator-associated pneumonia (VAP) is a serious complication of mechanical ventilation therapy that affects patients' treatments and prognoses. Owing to its excellent data mining capabilities, artificial intelligence (AI) has been increasingly used to predict VAP. Objective: This paper reviews VAP prediction models that are based on AI, providing a reference for the early identification of high-risk groups in future clinical practice. Methods: A scoping review was conducted in accordance with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. The Wanfang database, the Chinese Biomedical Literature Database, Cochrane Library, Web of Science, PubMed, MEDLINE, and Embase were searched to identify relevant articles. Study selection and data extraction were independently conducted by 2 reviewers. The data extracted from the included studies were synthesized narratively. Results: Of the 137 publications retrieved, 11 were included in this scoping review. The included studies reported the use of AI for predicting VAP. All 11 studies predicted VAP occurrence, and studies on VAP prognosis were excluded. Further, these studies used text data, and none of them involved imaging data. Public databases were the primary sources of data for model building (studies: 6/11, 55%), and 5 studies had sample sizes of <1000. Machine learning was the primary algorithm for studying the VAP prediction models. However, deep learning and large language models were not used to construct VAP prediction models. The random forest model was the most commonly used model (studies: 5/11, 45%). All studies only performed internal validations, and none of them addressed how to implement and apply the final model in real-life clinical settings. Conclusions: This review presents an overview of studies that used AI to predict and diagnose VAP. AI models have better predictive performance than traditional methods and are expected to provide indispensable tools for VAP risk prediction in the future. However, the current research is in the model construction and validation stage, and the implementation of and guidance for clinical VAP prediction require further research.

Direct transmission of severe fever with thrombocytopenia syndrome virus from farm-raised fur animals to workers in Weihai, China.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease. SFTS virus (SFTSV) is transmitted by tick bites and contact with the blood or body fluids of SFTS patients. Animal-to-human transmission of SFTS has been reported in Japan, but not in China. In this study, the possible transmission route of two patients who fed and cared for farm-raised fur animals in a mink farm was explored. METHOD: An epidemiological investigation and a genetic analysis of patients, animals and working environment were carried out. RESULTS: It was found that two patients had not been bitten by ticks and had no contact with patients infected with SFTS virus, but both of them had skinned the dying animals. 54.55% (12/22) of the farm workers were positive for SFTS virus antibody. By analyzing the large, medium and small segments sequences, the viral sequences from the two patients, animals and environments showed 99.9% homology. CONCLUSION: It is suspected that the two patients may be directly infected by farm-raised animals, and that the virus may have been transmitted by aerosols when skinning dying animals. Transmission by direct blood contacts or animal bites cannot be ignored.