Naked mesoporous rhodium nanospheres with glutathione depletion and photothermal capabilities for tumor therapy.

Pancreatic and colon cancer are malignant tumors of the digestive system that currently lack effective treatments. In cancer cells, a high level of glutathione (GSH) is indispensable to scavenge excessive reactive oxygen species (ROS) and detoxify xenobiotics, which make it a potential target for cancer therapy. GSH depletion has been proved to improve the therapeutic efficacy of photodynamic therapy. Here, we reported that naked mesoporous rhodium nanospheres (Rh MNs), prepared by soft template redox method, can act as GSH depletion agent and photothermal conversion agent to achieve synergistic therapy respectively. Different from conventional nanoagents, Rh MNs with the characteristics of easy synthesis, simple structure and multiple functions can decrease the GSH level in tumor and depict excellent photothermal ability with a high photothermal conversion efficiency (PTCE) up to 39%. Notably, multiple anti-tumor mechanisms in CT26 and BxPC-3 tumor models, include inhibited anti-apoptosis, DNA replication repair, and GSH synthesis are revealed, and the pancreatic tumor cure rate of the cooperative treatment group is 80%. Collectively, we developed Rh MNs to combine GSH depletion with photothermal therapy for cancer treatment.

Identification of true active sites in N-doped carbon-supported Fe2P nanoparticles toward oxygen reduction reaction.

Transition metal-based nanoparticles (NPs) are emerging as potential alternatives to platinum for catalyzing the oxygen reduction reaction (ORR) in zinc-air batteries (ZAB). However, the simultaneous coexistence of single-atom moieties in the preparation of NPs is inevitable, and the structural complexity of catalysts poses a great challenge to identifying the true active site. Herein, by employing in situ and ex situ XAS analysis, we demonstrate the coexistence of single-atom moieties and iron phosphide NPs in the N, P co-doped porous carbon (in short, Fe-N4-Fe2P NPs/NPC), and identify that ORR predominantly proceeds via the atomic-dispersed Fe-N4 sites, while the presence of Fe2P NPs exerts an inhibitory effect by decreasing the site utilization and impeding mass transfer of reactants. The single-atom catalyst Fe-N4/NPC displays a half-wave potential of 0.873 V, surpassing both Fe-N4-Fe2P NPs/NPC (0.858 V) and commercial Pt/C (0.842 V) in alkaline condition. In addition, the ZAB based on Fe-N4/NPC achieves a peak power density of 140.3 mW cm-2, outperforming that of Pt/C-based ZAB (91.8 mW cm-2) and exhibits excellent long-term stability. This study provides insight into the identification of true active sites of supported ORR catalysts and offers an approach for developing highly efficient, nonprecious metal-based catalysts for high-energy-density metal-air batteries.

Role of molybdenum in ameliorating busulfan-induced infertility in female mice.

BACKGROUND: Molybdenum (Mo) plays a crucial role in regulating normal physiological function. However, its potential effect on female infertility has received little attention. METHODS: In this study, we explored the potential molecular mechanisms of Mo's action on mouse ovaries and oocytes by establishing a busulfan-induced infertility model. Adult female Kunming mice were randomly divided into three groups: control, +busulfan, and +busulfan+Mo. After 30 days of busulfan treatment [Myleran, 20 mg/kg body weight ip], mice in the busulfan+Mo group were provided with 7.5 mg/L Mo per day in drinking water for an additional 42 days. On day 72, we examined the morphology of the oocytes and ovarian tissue after H&E staining, measured the concentrations of serum hormones by ELISA, and detected Bax, Bcl-2, caspase-3 and caspase-9 by immunohistochemical staining and western immunoblotting. We also assessed the oxidative stress in cells by measuring the activity of the antioxidant enzyme, SOD, the concentrations of MDA and LDH, and the percentage of apoptotic cells using kits. The number of litters born was counted after mating with male mice, and the organ coefficients were calculated after weighing on an analytic balance. RESULTS: Results showed that Mo treatment restored female reproductive hormone levels to near normal. Mo also significantly inhibited the mitochondrial stress-induced expression of apoptotic proteins. CONCLUSION: Our findings demonstrate that Mo treatment at a dose of 7.5 mg/L can ameliorate busulfan-induced infertility in female mice. These data may provide a reference for the development of treatments for female infertility.

Predicting the Compressive Strength of Sustainable Portland Cement-Fly Ash Mortar Using Explainable Boosting Machine Learning Techniques.

Unconfined compressive strength (UCS) is a critical property for assessing the engineering performances of sustainable materials, such as cement-fly ash mortar (CFAM), in the design of construction engineering projects. The experimental determination of UCS is time-consuming and expensive. Therefore, the present study aims to model the UCS of CFAM with boosting machine learning methods. First, an extensive database consisting of 395 experimental data points derived from the literature was developed. Then, three typical boosting machine learning models were employed to model the UCS based on the database, including gradient boosting regressor (GBR), light gradient boosting machine (LGBM), and Ada-Boost regressor (ABR). Additionally, the importance of different input parameters was quantitatively analyzed using the SHapley Additive exPlanations (SHAP) approach. Finally, the best boosting machine learning model's prediction accuracy was compared to ten other commonly used machine learning models. The results indicate that the GBR model outperformed the LGBM and ABR models in predicting the UCS of the CFAM. The GBR model demonstrated significant accuracy, with no significant difference between the measured and predicted UCS values. The SHAP interpretations revealed that the curing time (T) was the most critical feature influencing the UCS values. At the same time, the chemical composition of the fly ash, particularly Al2O3, was more influential than the fly-ash dosage (FAD) or water-to-binder ratio (W/B) in determining the UCS values. Overall, this study demonstrates that SHAP boosting machine learning technology can be a useful tool for modeling and predicting UCS values of CFAM with good accuracy. It could also be helpful for CFAM design by saving time and costs on experimental tests.

Stress-Strain Behavior and Strength Development of High-Amount Phosphogypsum-Based Sustainable Cementitious Materials.

Phosphogypsum is a common industrial solid waste that faces the challenges of high stockpiling and low utilization rates. This study focuses on the mechanical properties and internal characteristics of cementitious materials with a high phosphogypsum content. Specifically, we examined the effects of varying amounts of ground granulated blast furnace slag (5-28%), fly ash (5-20%), and hydrated lime (0.5-2%) on the stress-strain curve, unconfined uniaxial compressive strength, and elastic modulus (E50) of these materials. The test results indicate that increasing the ground granulated blast furnace slag content can significantly enhance the mechanical properties of phosphogypsum-based cementitious materials. Additionally, increasing the fly ash content can have a similar beneficial effect with an appropriate amount of hydrated lime. Furthermore, microscopic analysis of the cementitious materials using a scanning electron microscope revealed that the high sulfate content in phosphogypsum leads to the formation of calcium aluminate as the main product. Concurrently, a continuous reaction of the raw materials contributes to the strength development of the cementitious materials over time. The results could provide a novel method for improving the reusing phosphogypsum amount in civil engineering materials.

Mechanisms of Berberine in anti-pancreatic ductal adenocarcinoma revealed by integrated multi-omics profiling.

This study integrates pharmacology databases with bulk RNA-seq and scRNA-seq to reveal the latent anti-PDAC capacities of BBR. Target genes of BBR were sifted through TargetNet, CTD, SwissTargetPrediction, and Binding Database. Based on the GSE183795 dataset, DEG analysis, GSEA, and WGCNA were sequentially run to build a disease network. Through sub-network filtration acquired PDAC-related hub genes. A PPI network was established using the shared genes. Degree algorithm from cytoHubba screened the key cluster in the network. Analysis of differential mRNA expression and ROC curves gauged the diagnostic performance of clustered genes. CYBERSORT uncovered the potential role of the key cluster on PDAC immunomodulation. ScRNA-seq analysis evaluated the distribution and expression profile of the key cluster at the single-cell level, assessing enrichment within annotated cell subpopulations to delineate the target distribution of BBR in PDAC. We identified 425 drug target genes and 771 disease target genes, using 57 intersecting genes to construct the PPI network. CytoHubba anchored the top 10 highest contributing genes to be the key cluster. mRNA expression levels and ROC curves confirmed that these genes showed good robustness for PDAC. CYBERSORT revealed that the key cluster influenced immune pathways predominantly associated with Macrophages M0, CD8 T cells, and naïve B cells. ScRNA-seq analysis clarified that BBR mainly acted on epithelial cells and macrophages in PDAC tissues. BBR potentially targets CDK1, CCNB1, CTNNB1, CDK2, TOP2A, MCM2, RUNX2, MYC, PLK1, and AURKA to exert therapeutic effects on PDAC. The mechanisms of action appear to significantly involve macrophage polarization-related immunological responses.

Laccase: A Green Biocatalyst Offers Immense Potential for Food Industrial and Biotechnological Applications.

Laccase, a multipurpose biocatalyst, is widely distributed across all kingdoms of life and plays a key role in essential biological processes such as lignin synthesis, degradation, and pigment formation. These functions are critical for fungal growth, plant-pathogen interactions, and maintenance of soil health. Due to its broad substrate specificity, multifunctional nature, and environmentally friendly characteristics, laccase is widely employed as a catalyst in various green chemistry initiatives. With its ability to oxidize a diverse range of phenolic and nonphenolic compounds, laccase has also been found to be useful as a food additive and for assessing food quality parameters. Ongoing advancements in research and technology are continually expanding the recognition of laccase's potential to address global environmental, health, and energy challenges. This review aims to provide critical insights into the applications of laccases in the biotechnology and food industry.

Spatiotemporal dynamics of dinoflagellate communities in the Taiwan Strait and their correlations with micro-eukaryotic and bacterial communities.

Dinoflagellate blooms have negative adverse effects on marine ecosystems. However, our knowledge about the spatiotemporal distribution of dinoflagellate communities and their correlations with micro-eukaryotic and bacterial communities is still rare. Here, the sediment micro-eukaryotic and bacterial communities were explored in the Taiwan Strait (TWS) by 16S and 18S rRNA gene high-throughput sequencing. We found that the dinoflagellates were the most abundant algal group in TWS, and their relative abundance was higher in spring and autumn than in summer. Moreover, the species richness and community composition of dinoflagellates showed strong seasonal patterns. NO3-N and NH4-N had the strongest correlations with the spatiotemporal dynamics of community composition of dinoflagellates. The dinoflagellates had a significantly wider niche breadth than other algal groups for NH4-N, NO3-N and NO2-N, and therefore potentially contributed to a wider distribution range and high abundance in TWS. In addition, the dinoflagellates had stronger impacts on microeukaryotes than on bacteria for both community composition and species richness. However, the dinoflagellates showed close coexistence with bacteria but loose coexistence with microeukaryotes in spring co-occurrence networks. This close coexistence suggests the potentially strong synergy effects between dinoflagellates and bacteria in spring dinoflagellate blooms in TWS. Overall, this study revealed the distribution mechanisms of dinoflagellates in TWS based on niche breadth and also unveiled the different effects of dinoflagellates on micro-eukaryotic and bacterial communities.

Decolonization strategies for ESBL-producing or carbapenem-resistant Enterobacterales carriage: a systematic review and meta-analysis.

The prevalence of extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) and carbapenem-resistant Enterobacterales (CRE) has become a global public health problem. ESBL-E/CRE colonization can increase the risk of infection in patients and lead to poor disease prognosis. We conducted a systematic review and meta-analysis to evaluate current decolonization strategies regarding ESBL-E/CRE and their efficacy. A literature search was conducted until August 2023 on the five databases to review decolonization strategies associated with ESBL-E/CRE. A meta-analysis was conducted using RevMan 5.4 to compare differences in the decolonization strategy with placebo controls. The primary outcome was decolonization rates, with secondary outcomes of attributable death and adverse events. Quality of identified studies was determined using the Newcastle-Ottawa scale and cochrane risk assessment tool. Random and fixed effects meta-analyses were performed to calculate pooled value. A total of 25 studies were included. In five randomized controlled trial (RCT) studies, the decolonization effect of selective digestive decontamination(SDD) on ESBL-E/CRE at the end of treatment was significantly better in the experimental group than the controls [risk radio (RR): 3.30; 95% CI 1.78-6.14]. In three n-RCT studies, the decolonization effect in the experimental group was still better than the controls one month after SDD therapy [odds ratio (OR): 4.01; 95% CI 1.88-8.56]. The combined decolonization rates reported by six single-arm trial studies of SDD therapy ranged from 53.8 to 68.0%. Additionally, TSA analysis confirmed the effectiveness of SDD therapy. In studies on Faecal microbiota transplantation (FMT) therapy, the decolonization effect of the experimental group was significantly better than the controls 1 month after treatment (OR: 2.57; 95% CI 1.07-6.16). In studies without a control group and with varying follow-up times, the decolonization rates varied widely but indicated the effectiveness trend of FMT therapy (61.3-81.2%). Currently, research on the decolonization effect of probiotic therapy on ESBL-E/CRE is insufficient, and only a systematic review was conducted. SDD and FMT strategies have short-term benefits for ESBL-E/CRE decolonization, but long-term effects are unclear. The effect of probiotic therapy on ESBL-E/CRE decolonization is an interesting topic that still requires further investigation.

Biofunctionalized dissolvable hydrogel microbeads enable efficient characterization of native protein complexes.

The characterization of protein complex is vital for unraveling biological mechanisms in various life processes. Despite advancements in biophysical tools, the capture of non-covalent complexes and deciphering of their biochemical composition continue to present challenges for low-input samples. Here we introduce SNAP-MS, a Stationary-phase-dissolvable Native Affinity Purification and Mass Spectrometric characterization strategy. It allows for highly efficient purification and characterization from inputs at the pico-mole level. SNAP-MS replaces traditional elution with matrix dissolving during the recovery of captured targets, enabling the use of high-affinity bait-target pairs and eliminates interstitial voids. The purified intact protein complexes are compatible with native MS, which provides structural information including stoichiometry, topology, and distribution of proteoforms, size variants and interaction states. An algorithm utilizes the bait as a charge remover and mass corrector significantly enhances the accuracy of analyzing heterogeneously glycosylated complexes. With a sample-to-data time as brief as 2 hours, SNAP-MS demonstrates considerable versatility in characterizing native complexes from biological samples, including blood samples.

The impact of internet-based cognitive behavioral therapy on mental health outcomes and life in breast cancer patients: a systematic review and meta-analysis.

Background: Internet-based cognitive behavioral therapy(ICBT) improves the impact of breast cancer through online platforms, modular learning, goal setting, relaxation exercises, and other techniques. Compared to traditional cognitive behavioral therapy (CBT), ICBT offers advantages such as the convenience of flexible time and location choices and reduced manpower requirements. In recent years, research exploring the impact of ICBT on breast cancer patients has been increasing, with conflicting results across different studies. Therefore, the purpose of this study was to comprehensively examine the impact of ICBT on the psychological health and quality of life of breast cancer patients through a systematic review and meta-analysis. Methods: We searched ten databases in both English and Chinese, with the search period extending from the inception of the databases to December 30, 2023. Literature screening, bias risk assessment, data extraction, and evidence level evaluation were independently conducted by two researchers. All the data were analyzed using RevMan 5.4 and Stata 17.0 software. Results: A total of 2079 breast cancer patients were included in this study, of which 1171 patients received ICBT treatment. The results show that ICBT can reduce anxiety [SMD=-0.19, 95%CI (-0.37, -0.01), P=0.0008] and depression [SMD=-0.20, 95%CI (-0.37, -0.02), P=0.001], alleviate fatigue [SMD=-0.34, 95%CI (-0.67, -0.01), P=0.04], and improve quality of life [SMD=0.20, 95% CI (0.03, 0.38), P=0.02] in breast cancer patients. However, the intervention effects of ICBT on insomnia [SMD=-0.44, 95%CI (-0.93, 0.06), P=0.08] and sleep quality [SMD=-0.14, 95%CI (-0.30, 0.01), P=0.06] in breast cancer patients are not significant. The subgroup analysis showed that when the intervention period is longer than 8 weeks, the number of intervention modules exceeds 6, and a waitlist control group is included, there is a significant effect on reducing patients' anxiety and depression. However, the method of guidance and whether the intervention period exceeds 12 weeks are not related. Conclusion: ICBT can alleviate anxiety and depression in breast cancer patients, with the intervention effects being independent of the guidance method. Significant results were obtained when the intervention period was >8 weeks and the number of modules was >6. ICBT can reduce fatigue and improve quality of life in breast cancer patients, but its impact on sleep quality was not significant. More high-quality research is needed in the future. Systematic review registration: PROSPERO, identifier CRD42024494744.

Ecological protection makes the ecological Kuznets curve turning point come earlier.

Exploring the relationship between land use cover/change (LUCC) and ecosystem service value (ESV) under different future scenarios can provide guidance for selecting future development patterns and for the scientific utilization of land resources in the region. In this study, LUCC under different scenarios in the North Slope of Tianshan Mountain (NSTM) was simulated using the PLUS model. The ESV coefficients were adjusted for regional differences and social development factors to better reflect the actual situation in the study area. The interactions between LUCC, landscape pattern (LSP), and ESV were systematically analyzed, while at the same time, ESV and the level of economic development were fitted to the Ecological Kuznets Curve, which was then used to determine its trend and inflection point. The following conclusions were drawn: (1) Cropland and unused land are the main types of land use change in the NSTM, both historically and in the future. Cropland shows an increase in the natural development scenario and a decrease in the ecological protection scenario. Unused land shows an increase in the different development scenarios, indicating that unused land has higher development potential in the NSTM. NSTM shows a continuous decrease in ESV in the natural development scenario and a continuous increase in ESV in the ecological protection scenario. (2) LSP in both historical and future NSTM have evolved to show fragmentation, heterogeneity, and complexity in patch forms. However, this trend is slower in the ecological protection scenario than in the natural development scenario. LUCC, LSP, and ESV form an integrated framework of interactions, where LUCC influences ESV through LSP, and changes in ESV feedback to LUCC through LSP, which acts as a bridging mediator. (3) The Ecological Kuznets Curve of NSTM exhibits an N-shape, showing a clear overall rightward trend across different development scenarios at the annual level. At the interannual level, the curves for the natural development scenario are situated in the middle of the declining phase of the N-shape, with no ecological inflection point occurring during the study period. In contrast, the curves for the ecological protection scenario display a declining-ascending trend, with the ecological inflection point occurring when per capita GDP reaches 2.5 × 10^6 CNY.

Review of polysaccharides from Citrus medica L. var. sarcodactylis. (Fingered citron): Their extraction, purification, structural characteristics, bioactivity and potential applications.

Citrus medica L. var. sarcodactylis. (Fingered citron), commonly known as Buddha's hand, is a revered member of the Citrus genus belonging to the Rutaceae family with a long history in China. Fingered citron is known for its multifaceted utility as traditional herbal medicine, functional food and ornamental plant. Fingered citron polysaccharides (FCPs) are the key bioactive components of Citrus medica L. var. sarcodactylis, garnering global attention for their potential medicinal and culinary benefits. Various extraction methods like solvent extraction, ultrasound or microwave-assisted extraction have been used to obtain FCPs. Nonetheless, the structural characteristics of FCPs remain incompletely understood, necessitating further research and elucidation of the potential structure-activity relationship via the combined use of various advanced analytical techniques. Furthermore, FCPs exhibit diverse bioactivities, such as antioxidant activity, immunomodulatory effect, anti-inflammatory effect and gut microbiota regulatory activity, among others, positioning them as viable candidates for the therapeutic and health-promoting applications. Consequently, this review seeks to offer a comprehensive overview of FCPs, covering their extraction, purification, structural features, biological activities, and potential applications, underscoring the significant promise of FCPs as valuable natural compounds with multiple bioactive properties, advocating for their expanded utilization and integration into industry and therapeutics.

Effect of General Anesthesia vs Regional Anesthesia on Sleep Disturbance in Elderly Patients After Discharge from the Hospital for 3 Months.

Purpose: This study aims to investigate the impact of anesthetic methods on the occurrence of postoperative sleep disorders in elderly patients following their discharge from the hospital for 3 months. Patients and Methods: This retrospective observational cohort study included elderly patients aged >60 years who had undergone general and regional anesthesia from 1 June 2023 to 31 December 2023. These patients were then assessed for sleep by telephone callback using the Athens Insomnia Scale after discharge from the hospital three months later. The duration of pain and sleep disturbance experienced by patients following discharge was also recorded. Results: Following propensity score matching, 308 individuals were included in the study (154 in the GA group and 154 in the RA group). Compared with general anesthesia (11.7%), regional anesthesia (5.2%) reduced the prevalence of sleep disorders in elderly patients after discharge from the hospital. However, the duration of sleep disturbance and pain exhibited no statistically significant difference between the two groups (p=0.818; p=0.211). Conclusion: Regional anesthesia was associated with a reduction in the incidence of sleep disorders in elderly patients after discharge from the hospital for 3 months.

Inhibition of KPNA2 by ivermectin reduces E2F1 nuclear translocation to attenuate keratinocyte proliferation and ameliorate psoriasis-like lesions.

Psoriasis is a chronic, immune-mediated skin disease with a significant global prevalence. Karyopherin subunit alpha 2 (KPNA2), a nuclear transport protein involved in cellular activities such as differentiation, proliferation, apoptosis, and immune response, has emerged as a potential biomarker in several diseases. Our study found that KPNA2 was significantly upregulated in psoriasis patients and in imiquimod (IMQ)-induced psoriasis mouse models by bioinformatics and molecular biotechnology. In vivo, treatment with ivermectin, a KPNA2 inhibitor, significantly improved psoriasis symptoms in mice as evidenced by reduced erythema, desquamation, and skin thickness. Histopathological staining revealed decreased expression of KPNA2, K17, and Ki67 in ivermectin-treated mice, suggesting reduced abnormal differentiation and proliferation of keratinocytes. Transcriptome data and immunoblotting analysis showed that KPNA2 inhibition reduced inflammation and keratinocyte proliferation and differentiation in IMQ-induced mice. In vitro, EdU (5-ethynyl-2'-deoxyuridine) and flow cytometry experiments demonstrated that the downregulation of KPNA2 expression in HaCaT cells was capable of inhibiting the EGF (Epidermal Growth Factor)-induced activation of AKT/STAT3 signaling and keratinocytes proliferation. In addition, nuclear-cytoplasmic protein separation and immunofluorescence localization experiments showed that KPNA2 inhibition affected the nuclear translocation of E2F transcription factor 1 (E2F1), a process critical for keratinocyte proliferation. This study elucidated the role of KPNA2 in the pathogenesis of psoriasis and highlighted its potential as a target for future psoriasis therapies. These findings provide new insights into targeted therapy for psoriasis and have significant implications for future clinical treatment.

A separable double-layer self-pumping dressing containing astragaloside for promoting wound healing.

Some skin wounds often have many exudate. Ordinary single layer electrospunning nanofiber wound dressings often don't have enough capacity to absorb them. Therefore, a separable double layer electrospunning nanofiber dressing was developed in this work. The dressing had a separable feature that allowed the upper layer to be separated and removed after it had absorbed a significant amount of wound exudate. This dressing consisted of an upper layer of super hydrophilic sodium polyacrylate nanofibers and a bottom layer of 3D-structure coaxial nanofibers with encapsulated Astragaloside (AS). The results showed that nanofibers had better morphology. The water absorption rate, water vapor transmission rate and free radical scavenging rate of the double-layer dressings were 1461.71 ± 39.72 %, 1193.63 ± 134 g·m-2·day-1, and 63.35 ± 3.65 %, respectively. The double-layer nanofiber dressing achieved 65.69 ± 2.62 % and 75.10 ± 6.26 % inhibition against Staphylococcus aureus and Escherichia coli, respectively. The double-layer dressing had proliferative, migratory, and adhesive effects on L929 fibroblasts. And the double-layer dressing resulted in a 96.78 ± 1.0 % wound healing rate in rats after giving a 14 days treatment. Therefore, the 3D-structure separable double-layer wound dressing designed and prepared in this study was effective in promoting wound healing.

Molecular mechanism of proteolytic cleavage-dependent activation of CadC-mediated response to acid in E. coli.

Colonizing in the gastrointestinal tract, Escherichia coli confronts diverse acidic challenges and evolves intricate acid resistance strategies for its survival. The lysine-mediated decarboxylation (Cad) system, featuring lysine decarboxylase CadA, lysine/cadaverine antiporter CadB, and transcriptional activator CadC, plays a crucial role in E. coli's adaptation to moderate acidic stress. While the activation of the one-component system CadC and subsequent upregulation of cadBA operon in response to acid and lysine presence have been proposed, the molecular mechanisms governing the transition of CadC from an inactive to an active state remain elusive. Under neutral conditions, CadC is inhibited by forming a complex with lysine-specific permease LysP, stabilized in this inactive state by a disulfide bond. Our study unveils that, in an acidic environment, the disulfide bond in CadC is reduced by the disulfide bond isomerase DsbC, exposing R184 to periplasmic proteases, namely DegQ and DegP. Cleavage at R184 by DegQ and DegP generates an active N-terminal DNA-binding domain of CadC, which binds to the cadBA promoter, resulting in the upregulated transcription of the cadA and cadB genes. Upon activation, CadA decarboxylates lysine, producing cadaverine, subsequently transported extracellularly by CadB. We propose that accumulating cadaverine gradually binds to the CadC pH-sensing domain, preventing cleavage and activation of CadC as a feedback mechanism. The identification of DegP, DegQ, and DsbC completes a comprehensive roadmap for the activation and regulation of the Cad system in response to moderate acidic stress in E. coli.

Assessment of Noise Exposure and Risk of Hearing Loss for Young People in Amusement Arcades.

BACKGROUND: Amusement arcades are one of the most popular entertainment venues for young people, but excessive noise levels inside them could harm young people's hearing. The aim of this study is to assess the characteristics and risk of noise exposure for young people in amusement arcades and understand their knowledge of and attitudes towards safe listening. METHODS: In this study, noise measurement was conducted in five large amusement arcades to collect 40 noise samples. At the same time, questionnaires were used in each amusement arcade to investigate young players' social information, subjective perception, and cognition of noise-induced hearing loss (NIHL). RESULTS: The level of the noise samples ranged from 83.05 to 89.4 dBA. There are significant differences in noise levels between amusement arcades (P < 0.05), but there is no significant difference in noise levels between different games (P > 0.05). The subjective questionnaire survey shows that 61.9% of young people feel that the sound of video games is noisy or very noisy, but it is worth noting that 63.5% of them do not know or think that noise will not cause hearing loss, and 39.7% of people will choose to do nothing to help them endure the noise in such an environment. For safe listening, young people are more inclined to choose measures to stay in quiet areas and reduce the volume of game devices. CONCLUSIONS: The noise levels in most amusement arcades have exceeded the exposure limits recommended by the Environment Protection Agency (EPA); subjective questionnaires also indicate that internal noise levels may cause hearing loss, and young customers did not know enough about safe listening. For young people's hearing safety, these issues need more attention.

Comparing baseline VAF in circulating tumor DNA and tumor tissues predicting prognosis of patients with colorectal cancer liver metastases after curative resection.

INTRODUCTION: The prognostic value of baseline variant allele frequency (VAF) in circulating tumor DNA (ctDNA) of colorectal cancer liver metastases (CRLM) patients after curative resection was rarely investigated. METHODS: A single-center prospective study was performed to investigate the prognostic impact of baseline VAF in ctDNA and matched tumor tissues of CRLM patients after curative resection between May 2019 and May 2021 by the Illumina NovoSeq 6000 platform. The relationship of the tumor burden score (TBS) and the VAF in ctDNA and matched tumor tissues was evaluated by the Pearson correlation method. The survival curves of recurrence-free survival (RFS) and overall survival (OS) were plotted. Factors associated with RFS were calculated using Cox regression analysis, and an integrated prognostic model using significant baseline variables was proposed. RESULTS: There were 121 patients with baseline ctDNA and matched tumor tissues enrolled in the study. A total of 417 mutations spanning 20 genes were identified in baseline tumor tissues of 119/121 (98.3 %) cases. The overall mutations in tumor tissues were completely covered by ctDNA in 52 of 121(43.0 %) patients. Baseline VAF in ctDNA but not in tumor tissues was significantly correlated to TBS of CRLM (R = 0.36, p < 0.001). Significantly longer RFS but not OS was observed in patients with lower VAF in ctDNA compared to those with higher one (p < 0.001 and p = 0.33 respectively). Multivariate Cox regression analysis showed higher VAF in baseline ctDNA was an independent risk factor for RFS. An integrated prognostic model including baseline metastasis location and VAF in ctDNA outperformed the traditional CRS model in predicting RFS. CONCLUSION: Baseline VAF in ctDNA but not in tumor tissues influenced RFS of CRLM patients after curative resection.

A Rapid Detection Method for H3 Avian Influenza Viruses Based on RT-RAA.

The continued evolution of H3 subtype avian influenza virus (AIV)-which crosses the interspecific barrier to infect humans-and the potential risk of genetic recombination with other subtypes pose serious threats to the poultry industry and human health. Therefore, rapid and accurate detection of H3 virus is highly important for preventing its spread. In this study, a method based on real-time reverse transcription recombinase-aided isothermal amplification (RT-RAA) was successfully developed for the rapid detection of H3 AIV. Specific primers and probes were designed to target the hemagglutinin (HA) gene of H3 AIV, ensuring highly specific detection of H3 AIV without cross-reactivity with other important avian respiratory viruses. The results showed that the detection limit of the RT-RAA fluorescence reading method was 224 copies/response within the 95% confidence interval, while the detection limit of the RT-RAA visualization method was 1527 copies/response within the same confidence interval. In addition, 68 clinical samples were examined and the results were compared with those of real-time quantitative PCR (RT-qPCR). The results showed that the real-time fluorescence RT-RAA and RT-qPCR results were completely consistent, and the kappa value reached 1, indicating excellent correlation. For visual detection, the sensitivity was 91.43%, the specificity was 100%, and the kappa value was 0.91, which also indicated good correlation. In addition, the amplified products of RT-RAA can be visualized with a portable blue light instrument, which enables rapid detection of H3 AIV even in resource-constrained environments. The H3 AIV RT-RAA rapid detection method established in this study can meet the requirements of basic laboratories and provide a valuable reference for the early diagnosis of H3 AIV.