Persistent enrichment of multidrug-resistant Klebsiella in oral and nasal communities during long-term starvation.

BACKGROUND: The human oral and nasal cavities can act as reservoirs for opportunistic pathogens capable of causing acute infection. These microbes asymptomatically colonize the human oral and nasal cavities which facilitates transmission within human populations via the environment, and they routinely possess clinically significant antibiotic resistance genes. Among these opportunistic pathogens, the Klebsiella genus stands out as a notable example, with its members frequently linked to nosocomial infections and multidrug resistance. As with many colonizing opportunistic pathogens, the essential transmission factors influencing the spread of Klebsiella species among both healthy and diseased individuals remain unclear. RESULTS: Here, we explored a possible explanation by investigating the ability of oral and nasal Klebsiella species to outcompete their native microbial community members under in vitro starvation conditions, which could be analogous to external hospital environments or the microenvironment of mechanical ventilators. When K. pneumoniae and K. aerogenes were present within a healthy human oral or nasal sample, the bacterial community composition shifted dramatically under starvation conditions and typically became enriched in Klebsiella species. Furthermore, introducing K. pneumoniae exogenously into a native microbial community lacking K. pneumoniae, even at low inoculum, led to repeated enrichment under starvation. Precise monitoring of K. pneumoniae within these communities undergoing starvation indicated rapid initial growth and prolonged viability compared to other members of the microbiome. K. pneumoniae strains isolated from healthy individuals' oral and nasal cavities also exhibited resistance to multiple classes of antibiotics and were genetically similar to clinical and gut isolates. In addition, we found that in the absence of Klebsiella species, other understudied opportunistic pathogens, such as Peptostreptococcus, increased in relative abundance under starvation conditions. CONCLUSIONS: Our findings establish an environmental and microbiome community circumstance that allows for the enrichment of Klebsiella species and other opportunistic pathogens. Klebsiella's enrichment may hinge on its ability to quickly outgrow other members of the microbiome. The ability to outcompete other commensal bacteria and to persist under harsh environmental conditions could be an important factor that contributes to enhanced transmission in both commensal and pathogenic contexts. Video Abstract.

A convenient broad-host counterselectable system endowing rapid genetic manipulations of Kluyveromyces lactis and other yeast species.

Being generally regarded as safe, Kluyveromyces lactis has been widely taken for food, feed, and pharmaceutical applications, owing to its ability to achieve high levels of protein secretion and hence being suitable for industrial production of heterologous proteins. Production platform strains can be created through genetic engineering; while prototrophic cells without chromosomally accumulated antibiotics resistance genes have been generally preferred, arising the need for dominant counterselection. We report here the establishment of a convenient counterselection system based on a Frs2 variant, Frs2v, which is a mutant of the alpha-subunit of phenylalanyl-tRNA synthase capable of preferentially incorporating a toxic analog of phenylalanine, r-chloro-phenylalanine (4-CP), into proteins to bring about cell growth inhibition. We demonstrated that expression of Frs2v from an episomal plasmid in K. lactis could make the host cells sensitive to 2 mM 4-CP, and a Frs2v-expressing plasmid could be efficiently removed from the cells immediately after a single round of cell culturing in a 4-CP-contianing YPD medium. This Frs2v-based counterselection helped us attain scarless gene replacement in K. lactis without any prior engineering of the host cells. More importantly, counterselection with this system was proven to be functionally efficient also in Saccharomyces cerevisiae and Komagataella phaffii, suggestive of a broader application scope of the system in various yeast hosts. Collectively, this work has developed a strategy to enable rapid, convenient, and high-efficiency construction of prototrophic strains of K. lactis and possibly many other yeast species, and provided an important reference for establishing similar methods in other industrially important eukaryotic microbes.

Effects of nasal allergens and environmental particulate matter on brainstem metabolites and the consequence of brain-spleen axis in allergic rhinitis.

BACKGROUND: The growing consensus links exposure to fine particulate matter (PM2.5) with an increased risk of respiratory diseases. However, little is known about the additional effects of particulate matter on brainstem function in allergic rhinitis (AR). Furthermore, it is unknown to what extent the PM2.5-induced effects in the brainstem affect the inflammatory response in AR. This study aimed to determine the effects, mechanisms and consequences of brainstem neural activity altered by allergenic stimulation and PM2.5 exposure. METHODS: Using an AR model of ovalbumin (OVA) elicitation and whole-body PM2.5 exposure, the metabolic profile of the brainstem post-allergen stimulation was characterized through in vivo proton magnetic resonance imaging (1H-MRS). Then, the transient receptor potential vanilloid-1 (TRPV1) neuronal expression and sensitivity in the trigeminal nerve in AR were investigated. The link between TRPV1 expression and brainstem differential metabolites was also determined. Finally, we evaluated the mediating effects of brainstem metabolites and the consequences in the brain-spleen axis in the inflammatory response of AR. RESULTS: Exposure to allergens and PM2.5 led to changes in the metabolic profiles of the brainstem, particularly affecting levels of glutamine (Gln) and glutamate (Glu). This exposure also increased the expression and sensitivity of TRPV1+ neurons in the trigeminal nerve, with the levels of TRPV1 expression closely linked to the brainstem metabolism of Glu and Gln. Moreover, allergens increased the activity of p38, while PM2.5 led to the phosphorylation of p38 and ERK, resulting in the upregulation of TRPV1 expression. The brainstem metabolites Glu and Gln were found to partially mediate the impact of TRPV1 on AR inflammation, which was supported by the presence of pro-inflammatory changes in the brain-spleen axis. CONCLUSION: Brainstem metabolites are altered under allergen stimulation and additional PM2.5 exposure in AR via sensitization of the trigeminal nerve, which exacerbates the inflammatory response via the brain-splenic axis.

[Retracted] Association between vascular endothelial growth factor gene polymorphisms and the risk of osteonecrosis of the femoral head: Systematic review.

[This retracts the article DOI: 10.3892/br.2015.527.].

Exploring the potential mechanism of WuFuYin against hypertrophic scar using network pharmacology and molecular docking.

BACKGROUND: Hypertrophic scar (HTS) is dermal fibroproliferative disorder, which may cause physiological and psychological problems. Currently, the potential mechanism of WuFuYin (WFY) in the treatment of HTS remained to be elucidated. AIM: To explore the potential mechanism of WFY in treating HTS. METHODS: Active components and corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. HTS-related genes were obtained from the GeneCards, DisGeNET, and National Center for Biotechnology Information. The function of targets was analyzed by performing Gene Ontology and Kyoto Encyclopaedia of Genes and Genome (KEGG) enrichment analysis. A protein + IBM-protein interaction (PPI) network was developed using STRING database and Cytoscape. To confirm the high affinity between compounds and targets, molecular docking was performed. RESULTS: A total of 65 core genes, which were both related to compounds and HTS, were selected from multiple databases. PPI analysis showed that CKD2, ABCC1, MMP2, MMP9, glycogen synthase kinase 3 beta (GSK3B), PRARG, MMP3, and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG) were the hub targets and MOL004941, MOL004935, MOL004866, MOL004993, and MOL004989 were the key compounds of WFY against HTS. The results of KEGG enrichment analysis demonstrated that the function of most genes were enriched in the PI3K-Akt pathway. Moreover, by performing molecular docking, we confirmed that GSK3B and 8-prenylated eriodictyol shared the highest affinity. CONCLUSION: The current findings showed that the GSK3B and cyclin dependent kinase 2 were the potential targets and MOL004941, MOL004989, and MOL004993 were the main compounds of WFY in HTS treatment.

Effects of thinning and understory removal on soil phosphorus fractions in subtropical pine plantations.

Forest management changes the physical environments and nutrient dynamics and then regulates the forest productivity. Soil phosphorus (P) availability is critical for productivity in tropical and subtropical forests. However, it was still poorly understood how soil P content and fraction respond to various forest management practices in these regions. Here, we measured the soil total P, available P, and Hedley's P fractions, including inorganic and organic P (Pi and Po), in subtropical pine plantations treated with understory removal (UR), non-dominant species thinning (NDST) and dominant species thinning (DST) after nine years. Compared to plantations without management (CK), treatments such as UR, NDST, and DST decreased soil total P at 0-10 cm and soil available P at 0-10 cm and 10-20 cm. Increases in resin-Pi, NaOH-Pi, and C.HCl-Pi resulted in a higher total Pi in 0-10 cm (p < 0.05) in treated plots (UR, NDST, and DST) than in CK plots. UR, NDST, and DST treatments increased NaHCO3-Po and NaOH-Po (p < 0.05) but decreased C.HCl-Po at a depth of 0-10 cm. Regardless of management treatments, soil total P, available P, and P fractions in 0-10 cm showed higher contents than those in 10-20 cm. There were positive relationships between total P and total Po (p < 0.01) and between available P and total Pi. There were also positive relationships between total P, available P, NaHCO3-Pi, and NaOH-Pi (p < 0.05). In conclusion, forest management such as UR, NDST, and DST decreased soil total P and available P, and transforming soil P fractions to available P will meet the P demand following management in the pine plantations of subtropical China.

Lactate modulates zygotic genome activation through H3K18 lactylation rather than H3K27 acetylation.

In spite of its essential role in culture media, the precise influence of lactate on early mouse embryonic development remains elusive. Previous studies have implicated lactate accumulation in medium affecting histone acetylation. Recent research has underscored lactate-derived histone lactylation as a novel epigenetic modification in diverse cellular processes and diseases. Our investigation demonstrated that the absence of sodium lactate in the medium resulted in a pronounced 2-cell arrest at the late G2 phase in embryos. RNA-seq analysis revealed that the absence of sodium lactate significantly impaired the maternal-to-zygotic transition (MZT), particularly in zygotic gene activation (ZGA). Investigations were conducted employing Cut&Tag assays targeting the well-studied histone acetylation and lactylation sites, H3K18la and H3K27ac, respectively. The findings revealed a noticeable reduction in H3K18la modification under lactate deficiency, and this alteration showed a significant correlation with changes in gene expression. In contrast, H3K27ac exhibited minimal correlation. These results suggest that lactate may preferentially influence early embryonic development through H3K18la rather than H3K27ac modifications.

Discrimination of relatedness drives rice flowering and reproduction in cultivar mixtures.

The improvement of performance and yield in both cultivar and species mixtures has been well established. Despite the clear benefits of crop mixtures to agriculture, identifying the critical mechanisms behind performance increases are largely lacking. We experimentally demonstrated that the benefits of rice cultivar mixtures were linked to relatedness-mediated intraspecific neighbour recognition and discrimination under both field and controlled conditions. We then tested biochemical mechanisms of responses in incubation experiments involving the addition of root exudates and a root-secreted signal, (-)-loliolide, followed by transcriptome analysis. We found that closely related cultivar mixtures increased grain yields by modifying root behaviour and accelerating flowering over distantly related mixtures. Importantly, these responses were accompanied by altered concentration of signalling (-)-loliolide that affected rice transcriptome profiling, directly regulating root growth and flowering gene expression. These findings suggest that beneficial crop combinations may be generated a-priori by manipulating neighbour genetic relatedness in rice cultivar mixtures and that root-secreted (-)-loliolide functions as a key mediator of genetic relatedness interactions. The ability of relatedness discrimination to regulate rice flowering and yield raises an intriguing possibility to increase crop production.

Identification and functional analysis of a deduced geraniol synthase from Camphora officinarum.

The market demand for essential oil containing citral is increasing. Our research group identified a rare chemotype of Camphora officinarum whose leaves are high in citral content by examining over 1000 wild trees across the entire native distribution area of C. officinarum in China. Because C. officinarum is suitable for large-scale cultivation, it is therefore seen as a promising source of natural citral. However, the molecular mechanism of citral biosynthesis in C. officinarum is poorly understood. In this study, transcriptomic analyses of C. officinarum with different citral contents revealed a strong positive correlation between the expression of a putative geraniol synthase gene (CoGES) and citral content. The CoGES cDNA was cloned, and the CoGES protein shared high similarity with other monoterpene synthases. Enzymatic assays of CoGES with geranyl diphosphate (GPP) as substrate yielded geraniol as the single product, which is the precursor of citral. Further transient expression of CoGES in Nicotiana benthamiana resulted in a higher relative content of geranial and the appearance of a new substance, neral. These findings indicate that CoGES is a geraniol synthase-encoding gene, and the encoded protein can catalyze the transformation of GPP into geraniol, which is further converted into geranial and neral through an unknown mechanism in vivo. These findings expand our understanding of citral biosynthesis in Lauraceae plants. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01463-4.

Modified five times simulated body fluid for efficient biomimetic mineralization.

Simulated body fluid (SBF) is widely utilized in preclinical research for estimating the mineralization efficacy of biomaterials. Therefore, it is of great significance to construct an efficient and stable SBF mineralization system. The conventional SBF solutions cannot maintain a stable pH value and are prone to precipitate homogeneous calcium salts at the early stages of the biomimetic process because of the release of gaseous CO2. In this study, a simple but efficient five times SBF buffered by 5 % CO2 was developed and demonstrated to achieve excellent mineralized microstructure on a type of polymer-aligned nanofibrous scaffolds, which is strikingly similar to the natural human bone tissue. Scanning electron microscopy and energy-dispersive X-ray examinations indicated the growth of heterogeneous apatite with a high-calcium-to-phosphate ratio on the aligned nanofibers under 5 times SBF buffered by 5 % CO2. Moreover, X-ray diffraction spectroscopy and Fourier transform infrared analyses yielded peaks associated with carbonated hydroxyapatite with less prominent crystallization. In addition, the biomineralized aligned polycaprolactone nanofibers demonstrated excellent cell attachment, alignment, and proliferation characteristics in vitro. Overall, the results of this study showed that 5 × SBFs buffered by 5 % CO2 partial pressure are attractive alternatives for the efficient biomineralization of scaffolds in bone tissue engineering, and could be used as a model for the prediction of the bone-bonding bioactivity of biomaterials.

Systematic optimization of prime editing for the efficient functional correction of CFTR F508del in human airway epithelial cells.

Prime editing (PE) enables precise and versatile genome editing without requiring double-stranded DNA breaks. Here we describe the systematic optimization of PE systems to efficiently correct human cystic fibrosis (CF) transmembrane conductance regulator (CFTR) F508del, a three-nucleotide deletion that is the predominant cause of CF. By combining six efficiency optimizations for PE-engineered PE guide RNAs, the PEmax architecture, the transient expression of a dominant-negative mismatch repair protein, strategic silent edits, PE6 variants and proximal 'dead' single-guide RNAs-we increased correction efficiencies for CFTR F508del from less than 0.5% in HEK293T cells to 58% in immortalized bronchial epithelial cells (a 140-fold improvement) and to 25% in patient-derived airway epithelial cells. The optimizations also resulted in minimal off-target editing, in edit-to-indel ratios 3.5-fold greater than those achieved by nuclease-mediated homology-directed repair, and in the functional restoration of CFTR ion channels to over 50% of wild-type levels (similar to those achieved via combination treatment with elexacaftor, tezacaftor and ivacaftor) in primary airway cells. Our findings support the feasibility of a durable one-time treatment for CF.

VlMYB4 and VlCDF3 co-targeted the VlLOG11 promoter to regulate fruit setting in grape (Vitis vinifera L).

KEY MESSAGE: The VlLOG11 mediates the cytokinin signaling pathway to regulate grape fruit setting. Fruit set, as an accepted agronomic trait, is inextricably linked with fruit quality and yield. Previous studies have demonstrated that exogenous treatment with the synthetic cytokinin analog, forchlorfenuron (CPPU), significantly enhances fruit set. In this study, a significant reduction in endogenous cytokinins was found by measuring the content of cytokinins in young grape berries after CPPU treatment. LONELY GUYs (VlLOGs), a key cytokinin-activating enzyme working in the biosynthesis pathway of cytokinins, exhibited differential expression. Some differentially expressed VlLOGs genes were presented by RNA seq data and their functions and regulation patterns were further investigated. The results showed that VlLOG11 was differentially expressed in young grape berries after CPPU treatment. Overexpression of VlLOG11 in tomato increases the amount of fruit set, and upregulated the expression of genes associated with cytokinin signaling including SlHK4, SlHK5, SlHP3, SlHP4, SlPHP1, SlPHP2. VlMYB4 and VlCDF3 could regulate the expression of VlLOG11 by directly binding to its promoter in young grape berries during fruit set. These results strongly demonstrated that VlMYB4/VlCDF3-VlLOG11 regulatory module plays a key role in the process of fruit setting in grape. This provided a basis for the molecular mechanism of VlLOG11-mediated cytokinin biosynthesis in young grape fruit set.

Safety evaluation of outpatient vs inpatient unicompartmental knee arthroplasty: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the safety of outpatient and inpatient Unicompartmental Knee Arthroplasty (UKA) based on the incidence of adverse events. METHOD: A systematic search of the literature was performed in October 2022 on PubMed, Web of Science, Cochrane library, and Embase. The Meta package for R was used to perform the meta-analysis. RESULT: Five studies with a total of 26,301 patients were included. 5813 patients (22.1%) were treated with outpatient UKA, and 20,488 patients (77.9%) were treated with inpatient UKA. There were no statistically significant differences in the incidence of total complications (RR = 1.36, 95% CI = 0.64-2.89, Z = 0.79, P = 0.43), readmission (RR = 1.02, 95% CI = 0.40-2.60, Z = 0.05, P = 0.96), and venous thrombosis (RR = 1.43, 95% CI = 0.96-2.11, Z = 1.78, P = 0.08). Incidence rates were lower in outpatient UKA regarding urinary tract infection (RR = 1.48, 95% CI = 1.07-2.04, Z = 2.40, P = 0.02), pulmonary embolus (RR = 7.48, 95% CI = 1.80-31.17, Z = 2.76, P < 0.01), and transfusion (RR = 2.77, 95% CI = 1.63-4.71, Z = 3.78, P < 0.01). CONCLUSION: In summary, outpatient UKA shows lower incidences of hospital-acquired complications such urinary tract infection, pulmonary embolus, and transfusion. It's worth noting that the incidences of total complications, readmission, and venous thrombosis in outpatient UKA were not higher than the incidences of inpatient UKA, suggestting that outpatient UKA can be considered a safe alternative to inpatient UKA.

The emerging role of Piezo1 in the musculoskeletal system and disease.

Piezo1, a mechanosensitive ion channel, has emerged as a key player in translating mechanical stimuli into biological signaling. Its involvement extends beyond physiological and pathological processes such as lymphatic vessel development, axon growth, vascular development, immunoregulation, and blood pressure regulation. The musculoskeletal system, responsible for structural support, movement, and homeostasis, has recently attracted attention regarding the significance of Piezo1. This review aims to provide a comprehensive summary of the current research on Piezo1 in the musculoskeletal system, highlighting its impact on bone formation, myogenesis, chondrogenesis, intervertebral disc homeostasis, tendon matrix cross-linking, and physical activity. Additionally, we explore the potential of targeting Piezo1 as a therapeutic approach for musculoskeletal disorders, including osteoporosis, muscle atrophy, intervertebral disc degeneration, and osteoarthritis.

Conjugated microporous polymer for solid-phase extraction of neonicotinoid insecticides from environmental water samples.

Conjugated microporous polymers (CMPs) have unique characteristics and have been used in a range of fascinating applications in separation sciences. In this study, a CMP, designated as CMP-1, was synthesized via the Sonogashira-Hagihara coupling reaction using 1,3,5-triphenylbenzene and 1,4-dibromobenzene as building blocks. CMP-1 features a large surface area, abundant micropore structures, and excellent stability, making it a promising solid-phase extraction adsorbent for the efficient enrichment of neonicotinoid insecticides (NEOs). Under the optimized conditions, CMP-1 was combined with high-performance liquid chromatography and diode array detection to enable the detection of NEOs with a wide linear range (0.5-200 µg·L-1), a low detection limit (0.26-0.58 µg·L-1), and acceptable precision. The developed method was applied to determine spiked NEOs in three types of environmental water samples, with recoveries of 73.7%-112.0% and relative standard deviations of 0.6%-9.4%.

Validation of the Chinese version of the autism spectrum knowledge scale general population version (ASKSG) with a parent sample.

BACKGROUND: The early detection and diagnosis of autism spectrum disorder (ASD) in children are a first step in determining follow-up assessments and personalized treatment plans. Parents play an extremely crucial role in children's development; therefore, it is essential to identify a valid and reliable instrument to evaluate the knowledge of parents about ASD. The aim of this study was to translate and determine the psychometric properties of the Autism Spectrum Knowledge Scale General Population Version (ASKSG) with a parent sample. DESIGN AND METHODS: A cross-sectional study was conducted with 858 parents of children aged 0-14 years in China. The demographic characteristics form and ASKSG were used for data collection. The psychometric properties of the ASKSG were evaluated by examining reliability, exploratory factor analysis (EFA), categorical confirmatory factor analysis (CCFA), unidimensionality, person and item reliability, item fit and item difficulty, and item-person mapping. RESULTS: The Cronbach's alpha coefficient of the ASKSG was 0.865. In terms of EFA, principal component analysis revealed a fixed number of five factors, explaining 41.642% of the total variance. For the CCFA, the structure of the thematically derived five-factor model was observed to be a marginal fit to the data. The eigenvalue was 31.00, with a variance of 62.7%. The person reliability was 0.85, and the person separation was 2.38. The item reliability was 1.00, and the item separation was 15.02. The infit and outfit statistical analysis fell within acceptable ranges from 0.75 to 1.35, and the item difficulty ranged from -2.43 to 2.44. An item-person map with excellent targeting would be symmetric along the vertical axis from more difficult endorsement at the top (question 1 and question 20) to easier endorsement at the bottom (question 1). Some items do appear to function differently across sexes, and they assess the latent trait unequally across both sexes. CONCLUSIONS: The Chinese version of the ASKSG is a reliable and valid tool for assessing knowledge of parents about ASD. PRACTICE IMPLICATIONS: Chinese ASKSG now offers medical professionals and teachers a robust means of assessing parental knowledge about ASD. Therefore, professionals may use the scale to help them screen or identify parents who are in need of additional support or advice.

Distinct oral-associated gastric microbiota and Helicobacter pylori communities for spatial microbial heterogeneity in gastric cancer.

The gastric microbial community plays a fundamental role in gastric cancer (GC), and the two main anatomical subtypes of GC, non-cardia and cardia GC, are associated with different risk factors (Helicobacter pylori for non-cardia GC). To decipher the different microbial spatial communities of GC, we performed a multicenter retrospective analysis to characterize the gastric microbiota in 223 GC patients, including H. pylori-positive or -negative patients, with tumors and paired adjacent normal tissues, using third-generation sequencing. In the independent validation cohort, both dental plaque and GC tumoral tissue samples were collected and sequenced. The prevalence of H. pylori and oral-associated bacteria was verified using fluorescence in situ hybridization (FISH) assays in GC tumoral tissues and matched nontumoral tissues. We found that the vertical distribution of the gastric microbiota, at the upper, middle, and lower third sites of GC, was likely an important factor causing microbial diversity in GC tumor tissues. The oral-associated microbiota cluster, which included Veillonella parvula, Streptococcus oralis, and Prevotella intermedia, was more abundant in the upper third of the GC. However, H. pylori was more abundant in the lower third of the GC and exhibited a significantly high degree of microbial correlation. The oral-associated microbiota module was co-exclusive with H. pylori in the lower third site of the GC tumoral tissue. Importantly, H. pylori-negative GC patients with oral-associated gastric microbiota showed worse overall survival, while the increase in microbial abundance in H. pylori-positive GC patients showed no difference in overall survival. The prevalence of V. parvula in both the dental plaque and GC tissue samples was concordant in the independent validation phase. We showed that the oral-associated species V. parvula and S. oralis were correlated with overall survival. Our study highlights the roles of the oral-associated microbiota in the upper third of the GC. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for H. pylori-negative GCs. IMPORTANCE: Our study highlights the roles of the oral-associated microbiota in the upper third of gastric cancer (GC).We showed that the oral-associated species Veillonella parvula and Streptococcus oralis were correlated with overall survival. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for Helicobacter pylori-negative GCs.

Binary Host-induced Exciplex Enabled High Color-Rendering Index of 94 for Carbon Quantum Dot-Based White Light-Emitting Diodes.

White light-emitting diodes (WLEDs) with high color-rendering index (CRI, >90) are important for backlight displays and solid-state lighting applications. Although the well-developed colloidal quantum dots (QDs) based on heavy metals such as cadmium and lead are promising candidates for WLEDs, the low CRI still remains a significant limitation. In addition, the severe toxicity of heavy metals greatly limits their widespread use. Herein, the study demonstrates low-cost and environmentally friendly carbon quantum dots (CQDs)-based WLEDs that exhibit a high CRI of 94.33, surpassing that of conventional cadmium/lead-containing QD-based WLEDs. This achievement is attained through the employment of a binary host-induced exciplex strategy. The high hole/electron mobility and suitable energy levels of the donor and acceptor give rise to a broadband orange-yellow emission stemming from the exciplex. As the host, the binary exciplex is capable of contributing blue and orange-yellow emission components while efficiently mitigating the aggregation-induced quenching of CQDs. Meanwhile, CQDs effectively address the deep-red emission gap, enabling the realization of CQDs-based WLEDs with high CRI. These WLEDs also exhibit a remarkably low turn-on voltage of 2.8 V, a maximum luminance exceeding 2000 cd m- 2, a correlated color temperature of 4976 K, and Commission Internationale de l'Eclairage coordinates of (0.34, 0.32).

Pathological changes in the spleen of mice subjected to different time courses of restraint stress.

The objective of this study was to investigate spleen pathology and immune cell subset alterations in mice exposed to acute and chronic restraint stress over various timeframes. A deeper understanding of stress-induced spleen injuries can provide new insights into the mechanisms underlying stress-induced disorders. C57BL/6N mice were restrained for different durations (1, 3, 7, 14 and 21 days) for 6-8 h daily. The control mice were observed at the same time points. Post restraint, behavioural experiments were conducted to assess spleen weight, gross morphology and microscopic histological changes. Immunohistochemical staining was used to detect changes in glucocorticoid receptor (GR) expression, immune cell subsets and cell proliferation in response to stress. Our analysis revealed significant behavioural abnormalities in the stressed mice. In particular, there was an increase in the nuclear expression of GR beginning on Day 3, and it peaked on Day 14. The spleens of stressed mice displayed a reduction in size, disordered internal tissue structure and reduced cell proliferation. NK cells and M2-type macrophages exhibited immune cell subset alterations under stress, whereas T or B cells remained unaltered. Restraint stress can lead to pathomorphological alterations in spleen morphology, cell proliferation and immune cell counts in mice. These findings suggest that stress-induced pathological changes can disrupt immune regulation during stress.

Surgical resection due to poor outcome of the immunotherapy of a relapsed mediastinal liposarcoma: a case report.

The feasibility of surgery after immunotherapy for mediastinal liposarcoma remains uncertain. Besides, the case of immunotherapy for liposarcoma is still lacking. We report a case of recurrence after resection of a left mediastinal liposarcoma. After recurrence, one course of pembrolizumab plus anlotinib hydrochloride showed no tumor shrinkage, and genetic testing showed CDK4 amplification and PD-L1 TPS <1%; therefore, the plan was changed to one course of pembrolizumab plus palbociclib, but the tumor still did not shrink. Thus, second tumor resection was performed. In addition, the postoperative pathology was still well-differentiated liposarcoma. The significance of immunotherapy in liposarcoma still needs to be further explored. In the absence of surgical contraindications, secondary surgery might be feasible.