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Abstract Background Premature infants requiring mechanical ventilation and supplemental oxygen for respiratory support are at increased risk for bronchopulmonary dysplasia (BPD), wherein inflammation have been proposed as a driver of hyperoxia-induced injuries, including persistent loss of endothelial progenitor cells (EPCs), impaired vascularization and eventual alveolar simplification in BPD lungs. However, the underlying mechanisms linking these phenomena remain poorly defined. Methods We used clodronate liposomes to deplete macrophages in a mouse model of neonatal hyperoxia-induced lung injury to evaluate if EPC loss in BPD lungs could be an effect of macrophage infiltration. We further generated in vitro culture systems initiated with cord blood (CB)-derived CD34+ EPCs and neonatal macrophages either polarized from CB-derived monocytes or isolated from tracheal aspirates of human preterm infants requiring mechanical ventilation and oxygen supplementation, to identify EV-transmitted molecular mechanism that is critical for inhibitory actions of hyperoxic macrophages on EPCs. Results Initial experiments using mouse model identified the crucial role of macrophage infiltration in eliciting significant reduction of c-Kit+ EPCs in BPD lungs. Further examination of this concept in human system, we found that hyperoxia-exposed neonatal macrophages hamper human CD34+ EPC maintenance and impair endothelial function in the differentiated progeny via the EV transmission of miR-23a-3p. Notably, treatment with antagomiR-23a-3p to silence miR-23a-3p in vivo enhances c-Kit+ EPC maintenance, and increases capillary density, and consequently mitigates simplified alveolarization in BPD lungs. Conclusion Our findings highlight the importance of pulmonary intercellular communication in the pathophysiology of BPD, by identifying a linkage through vesicle transfer of miR-23a-3p from hyperoxic macrophages to EPCs, and thus demonstrating potential for novel therapeutic target in BPD.

Abstract The CLDN18-ARHGAP fusion gene is an oncogenic driver newly discovered in gastric cancer. It was detected in 9% (8/87) of gastric cancer patients in our center. An immunogenic peptide specifically targeting CLDN18-ARHGAP fusion gene was generated to induce neoantigen-reactive T cells, which was proved to have specific and robust anti-tumor capacity both in in vitro coculture models and in vivo xenograft gastric cancer models. Apart from the immunogenic potential, CLDN18-ARHGAP fusion gene was also found to contribute to immune suppression by inducing a regulatory T (Treg) cell-enriched microenvironment. Mechanistically, gastric cancer cells with CLDN18-ARHGAP fusion activate PI3K/AKT-mTOR-FAS signaling, which enhances free fatty acid production of gastric cancer cells to favor the survival of Treg cells. Furthermore, PI3K inhibition could effectively reverse Treg cells upregulation to enhance anti-tumor cytotoxicity of neoantigen-reactive T cells in vitro and reduce tumor growth in the xenograft gastric cancer model. Our study identified the CLDN18-ARHGAP fusion gene as a critical source of immunogenic neoepitopes, a key regulator of the tumor immune microenvironment, and immunotherapeutic applications specific to this oncogenic fusion.

Abstract Implicit poisoning in federated learning is a significant threat, with malicious nodes subtly altering gradient parameters each round, making detection difficult. This study investigates this problem, revealing that temporal analysis alone struggles to identify such covert attacks, which can bypass online methods like cosine similarity and clustering. Common detection methods rely on offline analysis, resulting in delayed responses. However, recalculating gradient updates reveals distinct characteristics of malicious clients. Based on this finding, we designed a privacy-preserving detection algorithm using trajectory anomaly detection. Singular values of matrices are used as features, and an improved Isolation Forest algorithm processes these to detect malicious behavior. Experiments on MNIST, FashionMNIST, and CIFAR-10 datasets show our method achieves 94.3% detection accuracy and a false positive rate below 1.2%, indicating its high accuracy and effectiveness in detecting implicit model poisoning attacks.

Abstract Tertiary lymphoid structures (TLSs) are defined as lymphoid aggregates formed in non-hematopoietic organs under pathological conditions. Similar to secondary lymphoid organs (SLOs), the formation of TLSs relies on the interaction between lymphoid tissue inducer (LTi) cells and lymphoid tissue organizer (LTo) cells, involving multiple cytokines. Heterogeneity is a distinguishing feature of TLSs, which may lead to differences in their functions. Growing evidence suggests that TLSs are associated with various diseases, such as cancers, autoimmune diseases, transplant rejection, chronic inflammation, infection, and even ageing. However, the detailed mechanisms behind these clinical associations are not yet fully understood. The mechanisms by which TLS maturation and localization affect immune function are also unclear. Therefore, it is necessary to enhance the understanding of TLS development and function at the cellular and molecular level, which may allow us to utilize them to improve the immune microenvironment. In this review, we delve into the composition, formation mechanism, associations with diseases, and potential therapeutic applications of TLSs. Furthermore, we discuss the therapeutic implications of TLSs, such as their role as markers of therapeutic response and prognosis. Finally, we summarize various methods for detecting and targeting TLSs. Overall, we provide a comprehensive understanding of TLSs and aim to develop more effective therapeutic strategies.

Abstract Passive source detection is a challenging problem in the shadow zone, where the sound is contributed primarily by bottom‐bounce rays. The conventional beamforming detector (CBFD), which utilises the sound energy from a single direction, suffers potential significant performance degradation in the multipath‐signal scenario. The matched field detector (MFD) offers optimal performance by exploiting full‐wave field characteristics but is limited due to its reliance on prior ocean environmental knowledge. The authors demonstrate that the incident sound on a near‐surface vertical line array in the shadow zone can be approximated as a coherent sum of two plane waves that share a symmetric arrival angle about the horizontal. This leads to the signal subspace depending only on the arrival angle, which the authors call the bottom‐bounce ray angle subspace (BRAS). With generalised likelihood ratio test theory, the authors further derive the BRAS detector (BRASD). It can utilise the full signal energy under the premise of weak environmental knowledge requirements and is generally superior to the CBFD. Simulation results in a typical deep‐water channel under different source‐position and array configuration conditions demonstrate the effectiveness of the BRASD and suggest that it can even offer a performance comparable to that of the MFD under specific conditions.

Abstract Background The triglyceride-glucose (TyG) index is linked to both the development and progression of diabetes, while obesity remains a significant risk factor for this disease. However, the relationship between the TyG index and overweight or obese diabetes remains unclear. Methods This study was a cross-sectional analysis of data from 40,633 participants with body mass index (BMI) ≥ 24 kg/m2 who were screened from January 2018 to December 2023 at Henan Provincial People’s Hospital. Participants were divided into groups of overweight or obese individuals with diabetes and those without diabetes according to the diabetes diagnostic criteria. The TyG index, the dependent variable, was determined using the equation ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. We explored the association between TyG index and diabetes in overweight or obese individuals through multivariate logistic regression, subgroup analysis, generalized additive models, smoothed curve fitting, and analysis of threshold effects. Results Patients who were overweight or obese and had diabetes had higher TyG index levels than those without diabetes. After adjusting for confounders, our findings indicated a significant association between the TyG index and the risk of diabetes in overweight or obese individuals [odds ratio (OR) = 7.38, 95% confidence interval (CI): 6.98–7.81]. There was a J-shaped nonlinear association between TyG index and diabetes. When TyG index was > 4.46, the risk of diabetes increased sharply. Notably, a high baseline TyG index (Q4 group) correlated with a notably greater risk of diabetes than did the Q1 group, with an OR of 22.72 (95% CI: 20.52–25.16). Subgroup analysis revealed that the association between TyG and diabetes was stronger in females than in males (OR = 7.57, 95% CI: 6.76–8.48,), more significant in individuals with a BMI of 24–28 kg/m2 than in those with a BMI ≥ 28 kg/m2 (OR = 8.40, 95% CI: 7.83–9.02), and increased with age (OR = 8.15, 95% CI: 7.25–9.17) (all P for interaction 4.46. Furthermore, factors such as sex, age, and BMI significantly influence the risk of diabetes in overweight or obese individuals. Specifically, older women with a BMI of 24–28 kg/m2 are at a greater risk of diabetes under similar TyG index conditions.

Abstract Objectives Existing data regarding the risk of COVID‐19 infection and its effects on seizure control in patients with epilepsy (PWE) are inconclusive. Our research aims to investigate the PWE who are susceptible to COVID‐19 and what factors contribute to seizure exacerbation. Methods From Dec 28, 2022 to Feb 19, 2023, a cross‐sectional questionnaire survey among adult PWE was conducted. The demographics, epilepsy‐related information, COVID‐19‐related variables, and seizure outcomes after COVID‐19 infection were collected. Multivariate logistic analyses were performed to determine the risk factors associated with COVID‐19 infection and exacerbated seizures. Results Of 1557 PWE, 829 (53.2%) were infected with COVID‐19 and 136 (16.4%) developed seizure exacerbation after COVID‐19 infection. Overweight/obesity (OR 1.372, 95% CI 1.075–1.753, p = 0.011), immunocompromised (OR 3.301, 95% CI 1.093–9.974, p = 0.031), active epilepsy (OR 1.700, 95% CI 1.378–2.097, p

Abstract Documenting tangible cultural heritage using 3D modeling techniques is gradually becoming an indispensable component of archaeological practice. The 3D modeling techniques based on photogrammetry and LiDAR scanning enable high-accuracy and high-realistic reconstruction of archaeological sites, and have been proven a powerful tool for documenting archaeological excavations. However, dynamically documenting an ongoing excavation using these techniques is still considered tedious, time-consuming, expensive, and dependent on expertise. Moreover, the application of 3D modeling techniques in archaeological excavations still faces some technical challenges, such as modeling with multi-source and multi-scale data, fusing local models at different times into a whole, achieving fast modeling while GPU workstations are not available in the field, and evaluating the quality of 3D models. As a result, there are still very few archaeological teams deeply engaged in dynamic documentation with 3D modeling techniques, and traditional drawing sketches and taking photographs still dominate. In these senses, documenting the archaeological excavation at the Yunxian Man site (located in Hubei, China) is an invaluable opportunity for exploration and practice. Archaeologists determined to conduct dynamically documenting at the beginning of the 6th excavation project for the site, and established a rotation system to reconcile physical excavation with digital preservation. Through repeated practice and communication, we proposed a workflow and pursued several new methods to enhance the feasibility of dynamically documenting, and obtained 4D models of the ongoing archaeological excavations. In 2022, the Yunxian Man site unearthed the most intact fossil of hominin cranium from about one million years ago in the Eurasian continent, preserving important and scarce anatomical features of early humans in Asia. As the original taphonomic context of the fossil corroded away during physical excavations, the digital documentation consisting of 4D models serves as permanent original data source in subsequent archaeological research. Moreover, we obtained cross-scale 3D models from geographical environment to archaeological site, excavation area, and cultural remains, and all of these 3D models are in an actual, unified coordinate framework. Thus, we can contribute to multidisciplinary cross-collaborative research through data sharing. Considering that digital documentations serve a great value in archaeological research, this paper focuses on sharing the workflow and methods to facilitate digital preservation for more archaeological projects.

Abstract The grid-based precipitation dataset is an important source for studying precipitation change in the high mountains of Asia due to where precipitation stations are sparse. It is essential to evaluate the accuracy of grid-based precipitation datasets in the high mountains of Asia before selecting an appropriate grid-based dataset. Therefore, this study comprehensively evaluated the precipitation errors of four commonly utilized precipitation datasets (multi-source weighted-ensemble precipitation (MSWEP), global precipitation climatology centre (GPCC), global precipitation measurement (GPM), and soil moisture to rain-advanced scatterometer (SM2RAIN-ASCAT)) in the high mountains of Asia from temporal and spatial perspectives. It then decomposed the precipitation errors to reveal their sources. The results showed that MSWEP, GPCC, GPM, and SM2RAIN-ASCAT overestimated precipitation amount and probability compared with station observations. Meanwhile, all precipitation data sets except MSWEP data underestimated precipitation in the dry season. In terms of the average values of the error metrics, GPCC performed the best. There was an evident annual periodicity in the error assessment metrics for the four precipitation data sets. Multiple linear regression analysis revealed that four precipitation-related factors (false alarm precipitation, missed amount of precipitation, precipitation detected presented, and precipitation detected event) explained the root mean square error values for four precipitation data sets, with precipitation detected presented having the largest weight. The root mean square error of each product exhibits periodic fluctuations with changes in precipitation quantity, attributed to the occurrences of precipitation detected presented and precipitation detected events. These findings provide useful reference information for correcting biases in precipitation data sets for high mountains of Asia.

Abstract Background Epithelial ovarian carcinoma (EOC) is a prevalent gynaecological malignancy. The prognosis of patients with EOC is related to acetylation modifications and immune responses in the tumour microenvironment (TME). However, the relationships between acetylation-related genes, patient prognosis, and the tumour immune microenvironment (TIME) are not yet understood. Our research aims to investigate the link between acetylation and the tumour microenvironment, with the goal of identifying new biomarkers for estimating survival of patients with EOC. Methods Using data downloaded from the tumour genome atlas (TCGA), genotypic tissue expression (GTEx), and gene expression master table (GEO), we comprehensively evaluated acetylation-related genes in 375 ovarian cancer specimens and identified molecular subtypes using unsupervised clustering. The prognosis, TIME, stem cell index and functional concentration analysis were compared among the three groups. A risk model based on differential expression of acetylation-related genes was established through minimum absolute contraction and selection operator (LASSO) regression analysis, and the predictive validity of this feature was validated using GEO data sets. A nomogram is used to predict a patient's likelihood of survival. In addition, different EOC risk groups were evaluated for timing, tumour immune dysfunction and exclusion (TIDE) score, stemness index, somatic mutation, and drug sensitivity. Results We used the mRNA levels of the differentially expressed genes related to acetylation to classify them into three distinct clusters. Patients with increased immune cell infiltration and lower stemness scores in cluster 2 (C2) exhibited poorer prognosis. Immunity and tumourigenesis-related pathways were highly abundant in cluster 3 (C3). We developed a prognostic model for ten differentially expressed acetylation-related genes. Kaplan–Meier analysis demonstrated significantly worse overall survival (OS) in high-risk patients. Furthermore, the TIME, tumour immune dysfunction and exclusion (TIDE) score, stemness index, tumour mutation burden (TMB), immunotherapy response, and drug sensitivity all showed significant correlations with the risk scores. Conclusions Our study demonstrated a complex regulatory mechanism of acetylation in EOC. The assessment of acetylation patterns could provide new therapeutic strategies for EOC immunotherapy to improve the prognosis of patients.

Abstract Background Lumbar puncture is challenging for patients with scoliosis. Previous ultrasound-assisted techniques for lumbar puncture used the angle of the probe as the needle trajectory; however, reproducing the angle is difficult and increases the number of needle manipulations. In response, we developed a technique that eliminated both the craniocaudal and lateromedial angulation of the needle trajectory to overall improve this technique. We assessed the feasibility and safety of this method in patients with scoliosis and identify factors related to difficult lumbar puncture. Methods Patients with spinal muscular atrophy and scoliosis who were referred to the anesthesia department for intrathecal nusinersen administrations were included. With a novel approach that utilized patient position and geometry, lumbar puncture was performed under ultrasound guidance. Success rates, performance times and adverse events were recorded. Clinical-demographic and spinal radiographic data pertaining to difficult procedures were analyzed. Results Success was achieved in all 260 (100%) lumbar punctures for 44 patients, with first pass and first attempt success rates of 70% (183/260) and 87% (226/260), respectively. Adverse events were infrequent and benign. Higher BMI, greater skin dural sac depth and smaller interlaminar size might be associated with greater difficulty in lumbar puncture. Conclusions The novel ultrasound-assisted horizontal and perpendicular interlaminar needle trajectory approach is an effective and safe method for lumbar puncture in patients with spinal deformities. This method can be reliably performed at the bedside and avoids other more typical and complex imaging such as computed tomography guided procedure.

Abstract Background Rabies is a fatal zoonotic disease whose pathogenesis has not been fully elucidated, and vaccination is the only effective method for protecting against rabies virus infection. Most inactivated vaccines are produced using Vero cells, which are African green monkey kidney cells, to achieve large-scale production. However, there is a potential carcinogenic risk due to nonhuman DNA contamination. Thus, replacing Vero cells with human diploid cells may be a safer strategy. In this study, we developed a novel 2BS cell-adapted rabies virus strain and analysed its sequence, virulence and immunogenicity to determine its application potential as a human diploid cell inactivated vaccine. Methods and results The 2BS cell-adapted rabies virus strain 2aG4-B40 was established by passage for 40 generations and selection of plaques in 2BS cells. RNA sequence analysis revealed that mutations in 2BS cell-adapted strains were not located at key sites that regulate the production of neutralizing antibodies or virulence in the aG strain (GQ412744.1). The gradual increase in virulence (remaining above 7.0 logLD50/ml from the 40th to 55th generation) and antigen further indicated that these mutations may increase the affinity of the adapted strains for human diploid cells. Identification tests revealed that the 2BS cell-adapted virus strain was neutralized by anti-rabies serum, with a neutralization index of 19,952. PrEP and PEP vaccination and the NIH test further indicated that the vaccine prepared with the 2aG4-B40 strain had high neutralizing antibody levels (2.24 to 46.67 IU/ml), immunogenicity (protection index 270) and potency (average 11.6 IU/ml). Conclusions In this study, a 2BS cell-adapted strain of the 2aG4 rabies virus was obtained by passage for 40 generations. The results of sequencing analysis and titre determination of the adapted strain showed that the mutations in the adaptive process are not located at key sequence regions of the virus, and these mutations may enhance the affinity of the adapted strain for human diploid cells. Moreover, vaccines made from the adapted strain 2aG4-B40 had high potency and immunogenicity and could be an ideal candidate rabies virus strain for inactivated vaccine preparation.

Abstract Background Tracheal tube cuff pressure will increase after pneumoperitoneum when the cuff is inflated with air, high pressure can cause tracheal mucosal damage. This prospective trial aimed to assess if inflating with normal saline or lidocaine can prevent increase of tracheal tube cuff pressure and tracheal mucosal damage in laparoscopic surgeries with general anesthesia. Whether changes of tracheal tube cuff transverse diameter (CD) can predict changes of tracheal tube cuff pressure. Methods Ninety patients scheduled for laparoscopic resection of colorectal neoplasms under general anesthesia were randomly assigned to groups air (A), saline (S) or lidocaine (L). Endotracheal tube cuff was inflated with room-temperature air in group A (n = 30), normal saline in group S (n = 30), 2% lidocaine hydrochloride injection in group L (n = 30). After intubation, tracheal tube cuff pressure was monitored by a calibrated pressure transducers, cuff pressure was adjusted to 25 cmH2O (T0.5). Tracheal tube cuff pressure at 15 min after pneumoperitoneum (T1) and 15 min after exsufflation (T2) were accessed. CD were measured by ultrasound at T0.5 and T1, the ability of ΔCD (T1-0.5) to predict cuff pressure was accessed. Tracheal mucous injury at the end of surgery were also recorded. Results Tracheal tube cuff pressure had no significant difference among the three groups at T1 and T2. ΔCD had prediction value (AUC: 0.92 [95% CI: 0.81–1.02]; sensitivity: 0.99; specificity: 0.82) for cuff pressure. Tracheal mucous injury at the end of surgery were 0 (0, 1.0) in group A, 0 (0, 1.0) in group S, 0 (0, 0) in group L (p = 0.02, group L was lower than group A and S, p = 0.03 and p = 0.04). Conclusions Compared to inflation with air, normal saline and 2% lidocaine cannot ameliorate the increase of tracheal tube cuff pressure during the pneumoperitoneum period under general anesthesia, but lidocaine can decrease postoperative tracheal mucosa injury. ΔCD measured by ultrasound is a predictor for changes of tracheal tube cuff pressure. Trial registration Chinese Clinical Trial Registry, identifier: ChiCTR2100054089, Date: 08/12/2021.

Selective activation of Pt(IV) prodrugs within tumors has emerged as a promising strategy in tumor treatment. Although progress has been made with photo- and ultrasound-activated Pt(IV) prodrugs, concerns remain over the non-specific activation of photosensitizers (PS) and the potential for phototoxicity and chemical toxicity. In this study, a sequential dual-locked Pt(IV) nano-prodrug that can be activated by both the acidic tumor microenvironment and light was developed. The Pt(IV) prodrug was prepared by conjugating PS-locked Pt(IV) to a polymeric core, which was then chelated with metallo iron to lock its photoactivity and form a metallo-nano prodrug. Under acidic tumor microenvironment conditions, the metallo-nano prodrug undergoes dissociation of iron, triggering a reduction process in oxaliplatin under light irradiation, resulting in the activation of both chemotherapy and photodynamic therapy (PDT). Additionally, the prodrug could induce metallo-triggered ferroptosis and polarization of tumor-associated macrophages (TAM), thereby enhancing tumor inhibition. The dual-lock strategy employed in a nanoparticle delivery system represents an expansion in the application of platinum-based anticancer drugs, making it a promising new direction in cancer treatment.

Many studies now indicate that brain disorders are associated with functional connectivity between brain regions, but the impact of interactions among functional connections on diseases remains to be explored. Moreover, existing models for analyzing the temporal and spatial attributes of fMRI data exhibit limitations in their efficacy. Currently, there is an absence of a comprehensive model capable of simultaneously capturing disease-related interactions within functional connectivity, fully leveraging the temporal and spatial characteristics of fMRI, and achieving superior diagnostic accuracy. To address these gaps, we propose a model to classify brain disorders that employs a novel algorithm and multimodal graph convolutional networks to process the temporal and spatial features of fMRI data separately, along with the demographic information. In the proposed model, a deep feature selection algorithm is employed to discover disease-related biomarkers and evaluate their impact on brain disorders. Remarkably, this approach has led to a classification accuracy of 80.66%, which surpasses the performance of graph neural networks by approximately 10%. Notably, our investigations have uncovered novel biomarkers linked to autism, with our findings corroborated by relevant literature. These achievements underscore the model's potential in revealing critical insights pertinent to autism, thereby facilitating groundbreaking experimental research in the field.

5-formylcytidine (f5C) is a unique post-transcriptional RNA modification found in mRNA and tRNA at the wobble site, playing a crucial role in mitochondrial protein synthesis and potentially contributing to the regulation of translation. Recent studies have unveiled that the f5C modifications may drive mitochondrial mRNA translation to power cancer metastasis. Accurate identification of f5C sites is essential for further unraveling their molecular functions and regulatory mechanisms, but there are currently no computational methods available for predicting their locations. In this study, we introduce an innovative ensemble approach, successfully enabling the computational recognition of Saccharomyces cerevisiae f5C. We conducted a comprehensive model selection process that involved multiple basic machine learning and deep learning algorithms such as recurrent neural networks, convolutional neural networks and Transformer-based models. Initially trained only on sequence information, these individual models achieved an AUROC ranging from 0.7104 to 0.7492. Through the integration of 32 novel domain-derived genomic features, the performance of individual models has significantly improved to an AUROC between 0.7309 and 0.8076. To further enhance accuracy and robustness, we then constructed the ensembles of these individual models with different combinations. The best performance attained by our ensemble models reached an AUROC of 0.8391. Shapley additive explanations were conducted to explain the significant contributions of genomic features, providing insights into the putative distribution of f5C across various topological regions and potentially paving the way for revealing their functional relevance within distinct genomic contexts. A freely accessible web server that allows real-time analysis of user-uploaded sites can be accessed at: www.rnamd.org/Resf5C-Pred.

Alongside the rapid advancement of artificial intelligence technologies, the complexity of society continues to escalate, and the design of multi-agent system rules becomes increasingly crucial, optimize participant engagement and addressing the issue of fairness and equilibrium win rates. The card game Legends of the Three Kingdoms (LTK), as a complex multi-agent system, represents an important abstraction of real-world scenarios, requiring the implementation of proper incentive mechanisms. Based on the mechanism and Stackelberg, this paper optimizes player strategies and system fairness. Firstly, we constructed a multi-agent Stackelberg game model for team battles. Then, we analyzed the impact of decision-making factors on players. Subsequently, we defined three kinds of fairness and improved the incentive mechanism. The results indicate that our mechanism optimizes participants' game behaviors, enhancing fairness among team players. Win rates were improved from 56.2% VS 43.8% to 51.4% VS 48.6%. With three different fairness measures, the win percentage fairness increased by 72 %, and the first elimination fairness increased by about 79 %. Our research provides a reference for understanding and analyzing complex computational models and facilitates the resolution of various resource allocation and system design issues.

Abstract Background Psychological empowerment notably impacts nurses’ work engagement and high-quality care. A spiritual climate is a work environment that respects individuals and encourages them to express personal views. Previous studies have shown that a spiritual climate enhances psychological empowerment, however, the relationship between them among the nursing population remains unclear. This study aimed to explore the effect of a spiritual climate on nurses’ psychological empowerment and provide a scientific basis for improving psychological empowerment among nurses. Methods A cross-sectional survey of 837 nurses from five hospitals in Sichuan Province, Southwest China, was conducted using a convenience sampling method; this survey included nurses’ demographic characteristics, the Psychological Empowerment Scale (PES), and the Chinese version of the Spiritual Climate Scale (C-SCS). The data were analysed using one-way analysis of variance (ANOVA), correlation analysis, and multiple linear regression. Results The sample of 837 nurses attained a psychological empowerment score of (45.49 ± 6.42) and a spiritual climate score of (75.25 ± 16.75). The one-way ANOVA revealed that psychological empowerment scores among nurses varied based on differences in age, department, years of work experience, professional title, level of work intensity, and children (yes/no). Pearson’s correlation analyses revealed a significant positive correlation between the spiritual climate and nurses’ psychological empowerment (r = 0.564, P

Abstract The secretagogin (SCGN) was originally identified as a secreted calcium-binding protein present in the cytoplasm. Recent studies have found that SCGN has a close relationship with cancer. However, its role in the occurrence, progression, and prognosis of clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, we utilized a mutual authentication method based on public databases and clinical samples to determine the role of SCGN in the progression and prognosis of ccRCC. Firstly, we comprehensively analyzed the expression characteristics of SCGN in ccRCC in several public databases. Subsequently, we systematically evaluated SCGN expression on 252 microarrays of ccRCC tissues from different grades. It was found that SCGN was absent in all the normal kidney tissues and significantly overexpressed in ccRCC tumor tissues. In addition, the expression level of SCGN gradually decreased with an increase in tumor grade, and the percentage of SCGN staining positivity over 50% was 86.7% (13/15) and 73.4% (58/79) in Grade1 and Grade2, respectively, while it was only 8.3% (12/144) in Grade3, and the expression of SCGN was completely absent in Grade4 (0/14) and distant metastasis group (0/4). Additionally, the expression of SCGN was strongly correlated with the patient's prognosis, with the higher the expression levels of SCGN being associated with longer overall survival and disease-free survival of patients. In conclusion, our results suggest that reduced expression of SCGN in cancer cells is correlated with the progression and prognosis of ccRCC.

Tendon-bone interface injuries pose a significant challenge in tissue regeneration, necessitating innovative approaches. Hydrogels with integrated supportive features and controlled release of therapeutic agents have emerged as promising candidates for the treatment of such injuries. In this study, we aimed to develop a temperature-sensitive composite hydrogel capable of providing sustained release of magnesium ions (Mg2+). We synthesized magnesium-Procyanidin coordinated metal polyphenol nanoparticles (Mg-PC) through a self-assembly process and integrated them into a two-component hydrogel. The hydrogel was composed of dopamine-modified hyaluronic acid (Dop-HA) and F127. To ensure controlled release and mitigate the “burst release” effect of Mg2+, we covalently crosslinked the Mg-PC nanoparticles through coordination bonds with the catechol moiety within the hydrogel. This crosslinking strategy extended the release window of Mg2+ concentrations for up to 56 days. The resulting hydrogel (Mg-PC@Dop-HA/F127) exhibited favorable properties, including injectability, thermosensitivity and shape adaptability, making it suitable for injection and adaptation to irregularly shaped supraspinatus implantation sites. Furthermore, the hydrogel sustained the release of Mg2+ and Procyanidins, which attracted mesenchymal stem and progenitor cells, alleviated inflammation, and promoted macrophage polarization towards the M2 phenotype. Additionally, it enhanced collagen synthesis and mineralization, facilitating the repair of the tendon-bone interface. By incorporating multilevel metal phenolic networks (MPN) to control ion release, these hybridized hydrogels can be customized for various biomedical applications.

Abstract Introduction Immunocompromised (IC) patients mount poor immune responses to vaccination. Higher-dose coronavirus disease 2019 (COVID-19) vaccines may offer increased immunogenicity. Methods A pairwise meta-analysis of 98 studies reporting comparisons of mRNA-1273 (50 or 100 mcg/dose) and BNT162b2 (30 mcg/dose) in IC adults was performed. Outcomes were seroconversion, total and neutralizing antibody titers, and cellular immune responses. Results mRNA-1273 was associated with a significantly higher seroconversion likelihood [relative risk, 1.11 (95% CI, 1.08, 1.14); P

In this paper, the fourth power mean values of the generalized quadratic Gauss sums associated with the $ 3 $-order and $ 4 $-order Dirichlet characters are given by using the properties of the Dirichlet characters and Gauss sums.

Abstract Aims This two-wave, longitudinal study aimed to examine the potential moderating and mediating effects of resilience on the association between perceived school bullying and psychotic-like experiences among Chinese sexual minority adolescents. Methods A total of 4192 senior high students were included and 984 (23.5%) of them were identified as a sexual minority (mean age = 16.68 years, SD = 0.71). Participants completed two online surveys during April 21 to May 12, 2021 and December 17 to 26, 2021, respectively, as well as completed self-report measures of sample characteristics, perceived school bullying, resilience, and psychotic-like experiences (including two dimensions: delusional experiences and hallucinatory experiences). Results Perceived school bullying and resilience were associated with psychotic-like experiences in sexual minority adolescents. Resilience mediated the relationship between perceived school bullying and subsequent psychotic-like experiences (b = 0.03, 95% CI = 0.01 ~ 0.04)/ delusional experiences (b = 0.03, 95% CI = 0.01 ~ 0.04)/ hallucinatory experiences (b = 0.02, 95% CI = 0.01 ~ 0.03). Additionally, resilience only moderated the associations of perceived school bullying with hallucinatory experiences (b = −0.06, 95% CI = −0.12 ~ −0.01). Conclusions These findings indicated that resilience plays a crucial role in mediating or moderating the relationship between perceived school bullying and psychotic-like experiences. Assessing and reducing school bullying, as well as promoting resilience, may have important clinical implications for reducing the risk of psychotic-like experiences in sexual minority adolescents.

Abstract Estimating fire emissions prior to the satellite era is challenging because observations are limited, leading to large uncertainties in the calculated aerosol climate forcing following the preindustrial era. This challenge further limits the ability of climate models to accurately project future climate change. Here, we reconstruct a gridded dataset of global biomass burning emissions from 1750 to 2010 using inverse analysis that leveraged a global array of 31 ice core records of black carbon deposition fluxes, two different historical emission inventories as a priori estimates, and emission-deposition sensitivities simulated by the atmospheric chemical transport model GEOS-Chem. The reconstructed emissions exhibit greater temporal variabilities which are more consistent with paleoclimate proxies. Our ice core constrained emissions reduced the uncertainties in simulated cloud condensation nuclei and aerosol radiative forcing associated with the discrepancy in preindustrial biomass burning emissions. The derived emissions can also be used in studies of ocean and terrestrial biogeochemistry.

Abstract. Background:. Lymph node staging of prostate cancer (PCa) is important for planning and monitoring of treatment. 18F-prostate specific membrane antigen positron emission tomography/computerized tomography (18F-PSMA PET/CT) has several advantages over 68Ga-PSMA PET/CT, but its diagnostic value requires further investigation. This meta-analysis focused on establishing the diagnostic utility of 18F-PSMA PET/CT for lymph node staging in medium/high-risk PCa. Methods:. We searched the EMBASE, PubMed, Cochrane library, and Web of Science databases from inception to October 1, 2022. Prostate cancer, 18F, lymph node, PSMA, and PET/CT were used as search terms and the language was limited to English. We additionally performed a manual search using the reference lists of key articles. Patients and study characteristics were extracted and the QUADAS-2 tool was employed to evaluate the quality of included studies. Sensitivity, specificity, the positive and negative likelihood ratio (PLR and NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and 95% confidence interval (CI) were used to evaluate the diagnostic value of 18F-PSMA PET/CT. Stata 17 software was employed for calculation and statistical analyses. Results:. A total of eight diagnostic tests including 734 individual samples and 6346 lymph nodes were included in this meta-analysis. At the patient level, the results of each consolidated summary were as follows: sensitivity of 0.57 (95% CI 0.39–0.73), specificity of 0.95 (95% CI 0.92–0.97), PLR of 11.2 (95% CI 6.6–19.0), NLR of 0.46 (95% CI 0.31–0.68), DOR of 25 (95% CI 11–54), and AUC of 0.94 (95% CI 0.92–0.96). At the lesion level, the results of each consolidated summary were as follows: sensitivity of 0.40 (95% CI 0.21–0.62), specificity of 0.99 (95% CI 0.95–1.00), PLR of 40.0 (95% CI 9.1–176.3), NLR of 0.61 (95% CI 0.42–0.87), DOR of 66 (95% CI 14–311), and AUC of 0.86 (95% CI 0.83–0.89). Conclusions:. 18F-PSMA PET/CT showed moderate sensitivity but high specificity in lymph node staging of medium/high-risk PCa. The diagnostic efficacy was almost equivalent to that reported for 68Ga-PSMA PET/CT. Registration:. International Prospective Register of Systematic Reviews (PROSPERO), No. CRD42023391101.

Objective: To evaluate the therapeutic effects of Epimedium brevicornu Maxim. (EBM, Yin Yang Huo) on breast cancer using network pharmacology and in vitro validation. It also aimed to explore the novel targets and mechanisms of EBM in the treatment of breast cancer to facilitate the discovery of new drugs and their clinical application. Methods: Network pharmacology was used to identify and screen the components and targets of EBM for breast cancer treatment. Molecular docking was further screened the effective components and targets of EBM. Wound-healing assays and flow cytometry analysis were used to detect the ability of two compounds to intervene in the migration and apoptosis of MDA-MB-231 cells, and their mechanism of action was further explored using western blotting experiments. Results: EBM contained 19 active components. Among them were β-anhydroicaritin (Anhy) and isoliquiritigenin (Iso), which were selected for in vitro experiments. Treatment resulted in a dose-dependent suppression of MDA-MB-231 cell viability, with an IC50 of 23.73 μmol/L for Iso and 21.28 μmol/L for Anhy. In the wound healing assay, cells in Anhy and Iso groups exhibited considerable inhibition of migration at 48 h. In flow cytometry analysis, treatment with Iso (20 μmol/L) for 96 h resulted in significantly higher levels of both early and late apoptosis in the Iso group than that in the control group (P = .004 and P = .014, respectively). Additionally, both Iso (20 μmol/L) and Anhy (10 and 20 μmol/L) induced cell necrosis at 96 h. Western blotting revealed that Anhy and Iso increased the expression of Bax and TBK1/NAK. Conclusion: These findings suggested that Anhy and Iso, the two components of EBM, inhibit MDA-MB-231 cell proliferation and migration of and induce their apoptosis, providing substantial support for future studies on breast cancer.

Abstract Gouty arthritis evokes joint pain and inflammation. Mechanisms driving gout pain and inflammation remain incompletely understood. Here we show that CXCL5 activates CXCR2 expressed on nociceptive sensory neurons to drive gout pain and inflammation. CXCL5 expression was increased in ankle joints of gout arthritis model mice, whereas CXCR2 showed expression in joint-innervating sensory neurons. CXCL5 activates CXCR2 expressed on nociceptive sensory neurons to trigger TRPA1 activation, resulting in hyperexcitability and pain. Neuronal CXCR2 coordinates with neutrophilic CXCR2 to contribute to CXCL5-induced neutrophil chemotaxis via triggering CGRP- and substance P-mediated vasodilation and plasma extravasation. Neuronal Cxcr2 deletion ameliorates joint pain, neutrophil infiltration and gait impairment in model mice. We confirmed CXCR2 expression in human dorsal root ganglion neurons and CXCL5 level upregulation in serum from male patients with gouty arthritis. Our study demonstrates CXCL5-neuronal CXCR2-TRPA1 axis contributes to gouty arthritis pain, neutrophil influx and inflammation that expands our knowledge of immunomodulation capability of nociceptive sensory neurons.

Abstract Promoting environmental concern among plastic waste entrepreneurs is a crucial step towards addressing the issue of plastic pollution effectively. To comprehend the techniques for enhancing environmental responsibility within this demographic, it is essential to examine the intergenerational shifts in environmental attitudes, which can provide valuable insights. This study investigates the intergenerational differences in two types of environmental concerns (i.e., ecological worldview and local environmental issue concern) by taking two generations of plastic waste business owners in Wuzhen Town, China, as a case. The roles of post-materialistic values, environmental knowledge, environmental risk exposure via new media, and community connection in mediating the relationships between generation and environmental concern were also examined in light of the Mindsponge theory. A paired-sample survey (N = 102) was utilized to collect data. The results of path analyses showed significant intergenerational differences in ecological worldview but insignificant intergenerational differences in local environmental issue concerns. While nondaily environmental knowledge and environmental risk exposure via new media significantly and positively mediated the relationship between generation and ecological worldview, community connection significantly and negatively mediated the relationship between generation and local environmental issue concern. Although a significant difference was found in the post-materialistic values between the two generations of plastic waste business owners, this variable did not significantly predict environmental concern.

Abstract The Phenome-Wide Association Study (PheWAS) is increasingly used to broadly screen for potential treatment effects, e.g., IL6R variant as a proxy for IL6R antagonists. This approach offers an opportunity to address the limited power in clinical trials to study differential treatment effects across patient subgroups. However, limited methods exist to efficiently test for differences across subgroups in the thousands of multiple comparisons generated as part of a PheWAS. In this study, we developed an approach that maximizes the power to test for heterogeneous genotype–phenotype associations and applied this approach to an IL6R PheWAS among individuals of African (AFR) and European (EUR) ancestries. We identified 29 traits with differences in IL6R variant-phenotype associations, including a lower risk of type 2 diabetes in AFR (OR 0.96) vs EUR (OR 1.0, p-value for heterogeneity = 8.5 × 10–3), and higher white blood cell count (p-value for heterogeneity = 8.5 × 10–131). These data suggest a more salutary effect of IL6R blockade for T2D among individuals of AFR vs EUR ancestry and provide data to inform ongoing clinical trials targeting IL6 for an expanding number of conditions. Moreover, the method to test for heterogeneity of associations can be applied broadly to other large-scale genotype–phenotype screens in diverse populations.

A 13 years and 1 month old child was admitted to the hospital with fulminant myocarditis. After admission, the child's condition deteriorated rapidly, with a rapid drop in blood pressure, alternating malignant arrhythmias, such as ventricular tachycardia and ventricular fibrillation, and then developed rapid cardiac arrest, which lasted for 62 min. Moreover, the child developed multiple organ failure (heart, kidney, brain, lungs, liver, gastrointestinal tract, and inflammatory system) with internal environmental disturbances, indicating critical conditions. After emergency extracorporeal membrane oxygenation (ECMO) and an intra-aortic balloon pump (IABP), continuous renal replacement therapy (CRRT) was administered to dehydrate and maintain homeostasis of the internal environment. The treatment plan was adjusted in a timely manner by performing standardized and detailed comprehensive respiratory, circulatory, anti-infection, volume, anticoagulation, skin, and physical rehabilitation treatments. The patient was transferred to the ICU 15 days later. The patient was successfully discharged from the hospital and resumed normal studies and life without any neurological sequelae. This case is the first study of ECMO combined with IABP and CRRT for the treatment of fulminant myocarditis combined with cardiac arrest and multiple organ failure in children, which has not yet been reported in the literature. The duration of the cardiac arrest in this case was extremely long (62 min), and the patient had a good prognosis for the resumption of normal life and growth. This case suggests the need for early recognition of fulminant myocarditis and early initiation of devices for circulatory function support, such as ECMO and IABP. Additionally, early initiation of CRRT can assist in precise volume management, reduce cerebral edema, stabilize the internal environment, and reduce organ functional damage, which is a strong guarantee of treatment.

Objective Few studies have examined the relationship between systemic oxidative stress and prostate cancer (PCa) risk. This study aimed to explore potential correlations between PCa and oxidative balance score (OBS), which measures systemic oxidative stress.Design A cross-sectional study.Setting The National Health and Nutrition Examination Survey.Participants A total of 8156 individuals were included in this study.Primary and secondary outcome measures Weighted logistic regression with multivariable adjustment and restricted cubic splines (RCS) were used to assess the correlation between PCa and OBS. A sensitivity analysis was conducted specifically on patients with PCa to verify the results.Results The prevalence of PCa was 2.55%. The multivariable logistic regression model revealed no correlation between OBS, dietary OBS, lifestyle OBS and PCa. Compared with the lowest quartile of OBS, the adjusted ORs for the highest quartile of OBS, dietary OBS and lifestyle OBS were 1.852 (95% CI 1.028–3.339), 1.565 (95% CI 0.841–2.913) and 1.575 (95% CI 0.915–2.710), respectively. Additionally, all p values for trend were greater than 0.05. Subgroup analysis revealed a consistent lack of association between OBS and PCa across various population settings. Furthermore, analysis using RCS confirmed this absence of association, indicating no significant relationship in either a linear or non-linear context. A sensitivity analysis focusing exclusively on patients with PCa showed a strong association (OR=2.737, p=0.008).Conclusion This cross-sectional study reveals no significant association between systemic oxidative stress, measured by OBS, and PCa risk. Notably, a sensitivity analysis focusing solely on PCa patients suggested a potential link, warranting further investigation.

BackgroundBroad T cell phenotypic alterations and potential dysfunctions were prominent in COVID-19. There are few and inconclusive data about the role of immune checkpoints for T cell exhaustion/activation during SARS-CoV-2 infection in multiple myeloma (MM) patients.MethodsWe tested T cell subsets and immune checkpoints in 177 MM patients with COVID-19, as well as in 32 healthy infected controls and 42 uninfected MM patients. The percentage of CD4+ and CD8+ subpopulation and immune checkpoints (PD-1, TIGIT, TIM-3, LAG-3, CTLA-4, OX40, and 4-1BB) were evaluated by flow cytometry.ResultsWe have found that pronounced lymphopenia and inverted CD4/CD8 ratio in severe COVID-19 patients were especially developed within the first month after infection. And T cell subset dysregulation was persistent in severe patients recovering from SARS-CoV-2 infection. Immune checkpoints on CD4+ T cells were variable and uncorrelated with the level of adaptive immunity, while the proportion of CD4+ T cells was positively correlated with humoral immune response. PD-1 and TIGIT on CD8+ T cells were significantly elevated in severe patients and sustained for more than 2 months, which was associated with impaired cellular immune function. Moreover, exhausted molecules PD-1 and TIGIT on T cells were reduced in immunotherapy patients.ConclusionThe prolonged T cell dysregulation after severe SARS-CoV-2 infection highlights the close surveillance from reinfection in MM patients even during convalescence. PD-1 and TIGIT on CD8+ T cells could be important prognostic factors to stratify prognosis in MM patients with COVID-19. Moreover, immunotherapy may downregulate the expression of exhausted checkpoints PD-1 and TIGIT, leading to T cell overactivation and severe COVID-19.

The ecological environment of wetlands in semi-arid regions has deteriorated, and vegetation succession has accelerated due to climate warming-induced aridification and human interference. The nutrient acquisition strategies and biomass allocation patterns reflect plant growth strategies in response to environmental changes. However, the impact of nutrient acquisition strategies on biomass allocation in successional vegetation remains unclear. We investigated 87 plant communities from 13 wetland sites in the semi-arid upper Yellow River basin. These communities were divided into three successional sequences: the herbaceous community (HC), the herbaceous–shrub mixed community (HSC), and the shrub community (SC). The nutrient composition of stems and leaves, as well as the biomass distribution above and belowground, were investigated. Results revealed that aboveground biomass increased with succession while belowground biomass decreased. Specifically, SC exhibited the highest stem biomass of 1,194.53 g m−2, while HC had the highest belowground biomass of 2,054.37 g m−2. Additionally, significant positive correlations were observed between leaf and stem biomasses in both HC and SC. The nitrogen (N) and phosphorus (P) contents within aboveground parts displayed an evident upward trend along the succession sequence. The highest N and P contents were found in SC, followed by HSC, and the lowest in HC. Stem N was negatively correlated with stem, leaf, and belowground biomass but positively correlated with root–shoot ratio. Leaf P displayed positive correlations with aboveground biomass while showing negative correlations with belowground biomass and root–shoot ratio. The ratios of C:N, C:P, and N:P in stem and leaf exhibited positive correlations with belowground biomass. The random forest model further demonstrated that stem N and leaf P exerted significant effects on aboveground biomass, while leaf P, stem N and P, and leaf C:P ratio had significant effects on belowground components. Additionally, the root–shoot ratio was significantly influenced by leaf P, leaf C:P ratio, and stem N, P, and C:P ratio. Therefore, the aboveground and belowground biomasses exhibited asynchronism across successional sequences, while plant nutrient acquisition strategies, involving nutrient levels and stoichiometric ratios, determined the biomass allocation pattern. This study offers valuable insights for assessing vegetation adaptability and formulating restoration plans in the semi-arid upper Yellow River basin.

Based on the focus on the role of reservoirs as carbon sources and sinks, this article explores their impact on the global carbon cycle. Reservoirs, which are “artificial lakes” created by human activities in rivers, are reviewed in terms of the key links in carbon cycling within reservoir areas, the influencing factors, and research methods related to carbon cycling and carbon emissions. By reviewing the literature on reservoir carbon cycling, we elucidate the mechanisms of carbon inputs, decomposition and transformation, carbon emissions, and carbon burial, summarizing the biogeochemical coupling processes of dissolved organic carbon (DOC), dissolved inorganic carbon (DIC), particulate organic carbon (POC), and particulate inorganic carbon (PIC) with hydrological conditions and nutrients. The study concludes that the reservoir carbon cycling process is influenced by the characteristics of the reservoirs themselves, hydrological and hydrodynamic conditions, physicochemical and nutrient conditions, and human activities. Additionally, we further clarify the applications of field sampling and analysis, modeling, remote sensing technology, and isotope techniques in reservoir carbon cycling. In the future, it is recommended to continue monitoring and simulating the reservoir carbon cycle processes on a long-term and large-scale basis, and to deeply explore the multifactorial mechanisms of reservoir construction in the global carbon cycle.

Trucks consume a lot of energy. Hybrid technology maintains a long range while realizing energy savings. Hybrid is therefore an effective energy-saving technology for trucks. Recovery of engine waste heat through the organic Rankine cycle further enhances engine efficiency and provides effective thermal management. However, the powertrain greatly increases the complexity of energy management system. In order to design an energy management system with high efficiency and robustness, this study proposes a deep reinforcement learning embedded rule-based energy management system. This method optimises the key parameters of the rule-based energy management system by inserting deep reinforcement learning into it. Therefore, this scheme combines the good optimization effect of deep reinforcement learning and the excellent robustness of rule. In order to verify the feasibility of this scheme, this study builds the system dynamic model and carries out a simulation study. Subsequently, a hybrid powertrain semi physical experimental bench was constructed and a rapid control prototype experimental study was carried out. The simulation results show that the deep reinforcement learning embedded rule-based energy management system can reduce the energy consumption by 4.31 % compared with the rule-based energy management system under the C-WTVC driving cycle. In addition, energy saving and safe operation can also be achieved under other unfamiliar untrained driving cycles. The rapid control prototype experimental study shows that the deep reinforcement learning embedded rule-based energy management system has good agreement in experiment and simulation, which demonstrates the potential for real vehicle engineering applications and promotes the engineering application of deep reinforcement learning.

Hyperuricemia (HUA), recognized as the fourth “high” condition following hypertension, hyperlipidemia, and hyperglycemia, is a metabolic disorder that severely impairs renal function. Spike lavender essential oil (SLEO) exhibits substantial anti-inflammatory and antioxidant activities and can inhibit xanthine oxidase (XOD), suggesting its potential therapeutic potential against HUA. This of this study aimed to analyze the chemical constituents of SLEO with potential efficacy in treating HUA and to explore their mechanisms of action. Gas chromatography-mass spectrometry (GC–MS) combined with a greedy algorithm identified linalool, β-pinene, and β-caryophyllene as key active components of SLEO. Through network pharmacology “weight coefficient” method, the NOD-like signaling pathway emerged as a significant mechanism for SLEO in treating HUA. Investigating an in vitro uric acid (UA)-induced HK-2 cell model revealed that SLEO effectively inhibited the production of IL-1β and IL-18 in the supernatant of HK-2 cells compared to the NLRP3 (antagonist MCC950). Additionally, a HUA rat model demonstrated that SLEO administration significantly reduced hyperuricemia pathological indicators, such as UA, XOD, and blood urea nitrogen (BUN) levels, with renal histopathological sections showing a marked reduction in following SLEO treatment. Metabolomics and transcriptomics analyses further highlighted significant changes in differential metabolites such as arachidonic acid and glycine, as well as the regulation of differential genes such as pycard and PTGS2 in rats.Immunohistochemistry, Western blotting, molecular docking and in vitro XOD activity inhibition assays elucidated the active components mechanisms of SLEO in treating HUA and associated renal inflammation. The findings concluded that SLEO mitigates HUA and renal inflammation by modulating the arachidonic acid metabolic pathway and the NF-κB signaling pathway. Moreover, linalool, β-pinene and β-caryophyllene in SLEO were shown to reduce UA production and lower UA levels in vivo by inhibiting the TLR4/NF-κB/NLRP3 pathway, thereby alleviating HUA-induced renal injury.

Abstract Chemoselective modification of specific residues within a given protein poses a significant challenge, as the microenvironment of amino acid residues in proteins is variable. Developing a universal molecular platform with tunable chemical warheads can provide powerful tools for precisely labeling specific amino acids in proteins. Cysteine and lysine are hot targets for chemoselective modification, but current cysteine/lysine‐selective warheads face challenges due to cross‐reactivity and unstable reaction products. In this study, a versatile fluorescent platform is developed for highly selective modification of cysteine/lysine under biocompatible conditions. Chloro‐ or phenoxy‐substituted NBSe derivatives effectively labeled cysteine residues in the cellular proteome with high specificity. This finding also led to the development of phenoxy‐NBSe phototheragnostic for the diagnosis and activatable photodynamic therapy of GSH‐overexpressed cancer cells. Conversely, alkoxy‐NBSe derivatives are engineered to selectively react with lysine residues in the cellular environment, exhibiting excellent anti‐interfering ability against thiols. Leveraging a proximity‐driven approach, alkoxy‐NBSe probes are successfully designed to demonstrate their utility in bioimaging of lysine deacetylase activity. This study also achieves integrating a small photosensitizer into lysine residues of proteins in a regioselective manner, achieving photoablation of cancer cells activated by overexpressed proteins.

Noroviruses are a group of non-enveloped single-stranded positive-sense RNA virus belonging to Caliciviridae family. They can be transmitted by the fecal-oral route from contaminated food and water and cause mainly acute gastroenteritis. Outbreaks of norovirus infections could be difficult to detect and investigate. In this study, we developed a simple threshold detection approach based on variations of the P2 domain of the capsid protein. We obtained sequences from the norovirus hypervariable P2 region using Sanger sequencing, including 582 pairs of epidemiologically-related strains from 35 norovirus outbreaks and 6402 pairs of epidemiologically-unrelated strains during the four epidemic seasons. Genetic distances were calculated and a threshold was performed by adopting ROC (Receiver Operating Characteristic) curve which identified transmission clusters in all tested outbreaks with 80 % sensitivity. In average, nucleotide diversity between outbreaks was 67.5 times greater than the diversity within outbreaks. Simple and accurate thresholds for detecting norovirus transmissions of three genotypes obtained here streamlines molecular investigation of norovirus outbreaks, thus enabling rapid and efficient responses for the control of norovirus.

Purpose Research on bone metastasis in esophageal cancer (EC) is relatively limited. Once bone metastasis occurs in patients, their prognosis is poor, and it severely affects their quality of life. Currently, there is a lack of convenient tumor markers for early identification of bone metastasis in EC. Our research aims to explore whether neutrophil-lymphocyte ratio (NLR) can predict bone metastasis in patients with EC. Methods Retrospective analysis of clinical indicators was performed on 604 patients with EC. They were divided into groups based on whether or not there was bone metastasis, and the patients’ coagulation-related tests, blood routine, tumor markers and other indicators were collected. The receiver operating characteristic curve (ROC) were used to determine the predictive ability of parameters such as NLR for bone metastasis in EC, and univariate and multivariate logistic regression analyses were conducted to determine the impact of each indicator on bone metastasis. Using binary logistic regression to obtain the predictive probability of NLR combined with tumor markers. Results ROC curves analysis suggested that the area under the curve (AUC) of the NLR was 0.681, with a sensitivity of 79.2% and a specificity of 52.6%, which can be used as a predictive factor for bone metastasis in EC. Multivariate logistic regression analysis showed that high NLR (odds ratio [OR]: 2.608, 95% confidence interval [CI]: 1.395-4.874, P = 0.003) can function as an independent risk factor for bone metastasis in patients with EC. Additionally, high PT, high APTT, high FDP, high CEA, high CA724, low hemoglobin, and low platelet levels can also predict bone metastasis in EC. When NLR was combined with tumor markers, the area under the curve was 0.760 (95% CI: 0.713-0.807, P

The gut microbiota plays a crucial role in host health and metabolism. This study explores the differences in gut microbiota and metabolites between domestic pigs (DP) and wild boars (WB) in urban environments. We analyzed gut microbial composition, metabolic profiles, virome composition, antibiotic resistance genes (ARGs), and human pathogenic bacteria (HPB) in both DP and WB. Our results revealed that DP exhibited a higher Firmicutes/Bacteroidetes ratio and were enriched in bacterial genera associated with domestication and modern feeding practices. Metabolomic analysis showed distinct profiles, with WB significantly enriched in the Pantothenate and CoA biosynthesis pathway, highlighting dietary and environmental influences on host metabolism. Additionally, DP had a distinct gut virome composition, particularly enriched in lytic phages of the Chaseviridae family. ARG analysis indicated a higher abundance of tetracycline resistance genes in DP, likely due to antibiotic use in pig farms. Furthermore, variations in HPB composition underscored potential health risks associated with contact with pig feces. These findings provide valuable insights into the microbial ecology of domestic pigs and wild boars, emphasizing the importance of these comparisons in identifying zoonotic pathogen transmission pathways and managing antibiotic resistance. Continued research in this area is essential for developing effective strategies to mitigate public health risks and promote sustainable livestock management practices.

When precision materials or components are moved or transported, traditional contact transport methods inevitably lead to some trouble such as wear, scarification, pollution and stress concentration. To solve these problems, a novel contact-free transport system based on Near-field Acoustic Levitation (NFAL) effect and Negative Pressure Absorption (NPA) technology is proposed. As the core component of transport system, the structure of object stage is presented and fabricated. Its working principle is revealed and its service behavior is investigated by theoretical, simulation and experimental methods. The load-carrying process and centripetal restoring process of the contact-free transport system is analyzed by mechanical models. To verify the levitation and centripetal restoring performance of the contact-free transport system under different conditions, a testing platform was built. In addition, the influence of dynamic parameters on the levitating and restoring performance of the transport system is studied experimentally, which will contribute to the guidance on design and optimization of dynamic parameters. The investigation on this contact-free transport method can provide a technical reference for the transport of disc-shaped components with an indication of accuracy requirements.

Abstract As an efficient and environmental‐friendly strategy, electrocatalytic oxidation can realize biomass lignin valorization by cleaving its aryl ether bonds to produce value‐added chemicals. However, the complex and polymerized structure of lignin presents challenges in terms of reactant adsorption on the catalyst surface, which hinders further refinement. Herein, NiCo‐based metal‐organic frameworks (MOFs) are employed as the electrocatalyst to enhance the adsorption of reactant molecules through π‐π interaction. More importantly, lattice strain is introduced into the MOFs via curved ligand doping, which enables tuning of the d‐band center of metal active sites to align with the reaction intermediates, leading to stronger adsorption and higher electrocatalytic activity toward bond cleavage within lignin model compounds and native lignin. When 2′‐phenoxyacetophenone is utilized as the model compound, high yields of phenol (76.3%) and acetophenone (21.7%) are achieved, and the conversion rate of the reactants reaches 97%. Following pre‐oxidation of extracted poplar lignin, >10 kinds of phenolic compounds are received using the as‐designed MOFs electrocatalyst, providing ≈12.48% of the monomer, including guaiacol, vanillin, eugenol, etc., and p‐hydroxybenzoic acid dominates all the products. This work presents a promising and deliberately designed electrocatalyst for realizing lignin valorization, making significant strides for the sustainability of this biomass resource.

Myeloid sarcoma (MS) occurs in patients with acute myeloid leukemia (AML). In rare cases, MS can represent a form of blast transformation in patients with myeloproliferative neoplasms (MPN), myelodysplastic neoplasms (MDS), or MDS/MPN. The most frequent chromosomal alterations in MS are t(8;21) or inv(16), with other alterations being reported. Cases of MS in Janus kinase 2 (JAK2)-positive MDS with fibrosis are exceedingly rare. Here, we describe such a case. To the best of our knowledge, this is the first report of a JAK2 V617F mutation-positive MDS case occurring concurrently with MS involving the posterior aspect of the left seventh rib. No clear association has been previously demonstrated between the intramedullary AML cytogenetics and extramedullary disease occurrence. Interestingly, samples from the intramedullary MDS and extramedullary mass in this patient presented the same JAK2 V617F mutation. Following a treatment regimen of azacitidine and venetoclax, the patient achieved complete remission. The chest CT scan showed that the seventh posterior rib mass disappeared. This case provides valuable information for the potential future treatment of this disease.

Nutrient bioavailability in the tumor microenvironment plays a pivotal role in tumor proliferation and metastasis. Among these nutrients, glutamine is a key substance that promotes tumor growth and proliferation, and its downstream metabolite asparagine is also crucial in tumors. Studies have shown that when glutamine is exhausted, tumor cells can rely on asparagine to sustain their growth. Given the reliance of tumor cell proliferation on asparagine, restricting its bioavailability has emerged as promising strategy in cancer treatment. For instance, the use of asparaginase, an enzyme that depletes asparagine, has been one of the key chemotherapies for acute lymphoblastic leukemia (ALL). However, tumor cells can adapt to asparagine restriction, leading to reduced chemotherapy efficacy, and the mechanisms by which different genetically altered tumors are sensitized or adapted to asparagine restriction vary. We review the sources of asparagine and explore how limiting its bioavailability impacts the progression of specific genetically altered tumors. It is hoped that by targeting the signaling pathways involved in tumor adaptation to asparagine restriction and certain factors within these pathways, the issue of drug resistance can be addressed. Importantly, these strategies offer precise therapeutic approaches for genetically altered cancers.

Osteoporosis is a prevalent bone metabolic disease that poses a significant challenge to global human health. Jaw osteoporosis, characterized by microstructural damage of the jaw resulting from various factors, is one of the common manifestations of this condition. Recent studies have demonstrated that jaw osteoporosis has multifaceted effects on oral health and can negatively impact conditions such as periodontitis, oral implantation, orthodontic treatment, and wound healing. However, there are still some limitations in the conventional treatment of osteoporosis. For instance, while bisphosphonates can enhance bone quality, they may also lead to osteonecrosis of the jaw, which poses a potential safety hazard in oral diagnosis and treatment. In recent years, considerable attention has been focused on improving the pathological condition of jaw osteoporosis. Treatment strategies such as gut microbial regulation, extracellular vesicles, molecular targeted therapy, herbal medicine, mechanical stimulation are expected to enhance efficacy and minimize adverse reactions. Therefore, understanding these effects and exploring novel treatments for jaw osteoporosis may provide new insights for oral health maintenance and disease treatment. This article reviews the impact of jaw osteoporosis on oral health and describes the limitations associated with current methods. It also discusses emerging perspectives on treatment, offering a comprehensive overview of the challenges and future directions in managing jaw osteoporosis.

IntroductionExit selection is crucial in indoor emergency evacuation. Domestic and foreign scholars have found that exit choice behavior is influenced by three factors: environmental factors, social interactions, and individual internal factors. Previous studies have shown that in addition to a single environmental factor affecting exit decisions, the influence of other available exit options in the context can ultimately lead to a reversal of exit decisions -The context effect. However, the impact of context effects on exit decisions in emergency situations has not been thoroughly explored. Therefore, this article identifies three basic independent variables: context effects, crowd flows, and gender differences, to study the exit decisions of different gender groups facing different crowd flows, as well as how context effects affect existing exit decisions.MethodsIn this paper, we used virtual reality technology to construct an indoor fire scene and designed a total of 15 virtual experiments with different crowd distribution or context effects. 131 participants were divided into two groups, male and female, and their exit decisions were observed under different crowd flows and contextual effects.ResultsThe research results show that: 1) Both men and women have an innate preference to avoid crowded exits, and the proportion of following crowd evacuation significantly decreases when there are crowded crowds in the scene; 2) The exit decisions of female participants are more influenced by the crowd, while men tend to be more influenced by context effects when evacuating independently; 3) The context effects on exit decisions in emergency situations is statistically significant, and this performance is more significant in the male population. Further analysis reveals that similarity effects have a more significant impact on exit decisions than attraction effects.DiscussionsThese findings provide deeper insights into the exit choice behavior of the population and may contribute to the design of safe exits in indoor buildings. In addition, this article emphasizes the importance of context effects and provides a foundation for future research.

Purpose: This study aimed to investigated the key chemical components and the effect of the aqueous extract of Schisandra sphenanthera (SSAE) on alcoholic liver disease (ALD) and the related molecular mechanism. Methods: This study employed UPLC-Q-TOF-MS/MS to identify the chemical compositions in SSAE. ALD rat model was established through oral administration of white spirit. Transcriptome sequencing, weighted gene co-expression network construction analysis (WGCNA), and network pharmacology were used to predict key compositions and pathways targeted by SSAE for the treatment of ALD. Enzyme-linked immunosorbent assay (ELISA), biochemical kits, hematoxylin-eosin (HE) staining, Western blotting (WB) analysis, and immunohistochemical analysis were used to validate the mechanism of action of SSAE in treating ALD. Results: Active ingredients such as schisandrin A, schisandrol A, and schisandrol B were found to regulate the PI3K/AKT/IKK signaling pathway. Compared to the model group, the SSAE group demonstrated significant improvements in cellular solidification and tissue inflammation in the liver tissues of ALD model rats. Additionally, SSAE regulated the levels of a spartate aminotransferase (AST), alanine aminotransferase (ALT), alcohol dehydrogenase (ADH), and aldehyde Dehydrogenase (ALDH) in serum (P

Summary: The unfolded protein response (UPR) relieves endoplasmic reticulum (ER) stress through multiple strategies, including reducing protein synthesis, increasing protein folding capabilities, and enhancing misfolded protein degradation. After a multi-omics analysis, we find that signal recognition particle 14 (SRP14), an essential component of the SRP, is markedly reduced in cells undergoing ER stress. Further experiments indicate that SRP14 reduction requires PRKR-like ER kinase (PERK)-mediated eukaryotic translation initiation factor 2α (eIF2α) phosphorylation but is independent of ATF4 or ATF3 transcription factors. The decrease of SRP14 correlates with reduced translocation of fusion proteins and endogenous cathepsin D. Enforced expression of an SRP14 variant with elongation arrest capability prevents the reduced translocation of cathepsin D in stressed cells, whereas an SRP14 mutant without the activity does not. Finally, overexpression of SRP14 augments the UPR and aggravates ER-stress-induced cell death. These data suggest that translocational attenuation mediated by the PERK-SRP14 axis is a protective measure for the UPR to mitigate ER stress.

Abstract Introduction The mRNA vaccines mRNA-1273 and BNT162b2 demonstrated high efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in phase 3 clinical trials, including among older adults. To inform coronavirus disease 2019 (COVID-19) vaccine selection, this systematic literature review (SLR) and meta-analysis assessed the comparative effectiveness of mRNA-1273 versus BNT162b2 in older adults. Methods We systematically searched for relevant studies reporting COVID-19 outcomes with mRNA vaccines in older adults aged ≥ 50 years by first cross-checking relevant published SLRs. Based on the cutoff date from a previous similar SLR, we then searched the WHO COVID-19 Research Database for relevant articles published between April 9, 2022, and June 2, 2023. Outcomes of interest were SARS-CoV-2 infection, symptomatic SARS-CoV-2 infection, severe SARS-CoV-2 infection, COVID-19–related hospitalization, and COVID-19–related death following ≥ 2 vaccine doses. Random effects meta-analysis models were used to pool risk ratios (RRs) across studies. Heterogeneity was evaluated using chi-square testing. Evidence certainty was assessed per GRADE framework. Results Twenty-four non-randomized real-world studies reporting clinical outcomes with mRNA vaccines in individuals aged ≥ 50 years were included in the meta-analysis. Vaccination with mRNA-1273 was associated with significantly lower risk of SARS-CoV-2 infection (RR 0.72 [95% confidence interval (CI) 0.64‒0.80]), symptomatic SARS-CoV-2 infection (RR 0.72 [95% CI 0.62‒0.83]), severe SARS-CoV-2 infection (RR 0.67 [95% CI 0.57‒0.78]), and COVID-19–related hospitalization (RR 0.65 [95% CI 0.53‒0.79]) but not COVID-19–related death (RR 0.80 [95% CI 0.64‒1.00]) compared with BNT162b2. There was considerable heterogeneity between studies for all outcomes (I 2 > 75%) except death (I 2 = 0%). Multiple subgroup and sensitivity analyses excluding specific studies generally demonstrated consistent results. Certainty of evidence across outcomes was rated as low (type 3) or very low (type 4), reflecting the lack of randomized controlled trial data. Conclusion Meta-analysis of 24 observational studies demonstrated significantly lower risk of asymptomatic, symptomatic, and severe infections and hospitalizations with the mRNA-1273 versus BNT162b2 vaccine in older adults aged ≥ 50 years.