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The riffle beetle genus Sinonychus Jäch & Boukal, 1995 (Elminae, Macronychini) includes only three species from East Asia. In this paper, two new species, S. lipinae sp. nov. and S. luodianensis sp. nov., are described from Guizhou Province, China. Illustrations of the new species and a key to all five Sinonychus species are also provided.

Abstract Background The practical application of infectious disease emergency plans in mental health institutions during the ongoing pandemic has revealed significant shortcomings. These manifest as chaotic management of mental health care, a lack of hospital infection prevention and control (IPC) knowledge among medical staff, and unskilled practical operation. These factors result in suboptimal decision-making and emergency response execution. Consequently, we have developed a digital-based emergency prevention and control system to reinforce IPC management in psychiatric hospitals and enhance the hospital IPC capabilities of medical staff. Methods The system incorporates modern technologies such as cloud computing, big data, streaming media, and knowledge graphs. A cloud service platform was established at the PaaS layer using Docker container technology to manage infectious disease emergency-related services. The system provides application services to various users through a Browser/Server Architecture. The system was implemented in a class A tertiary mental health center from March 1st, 2022, to February 28th, 2023. Twelve months of emergency IPC training and education were conducted based on the system. The system’s functions and the users’ IPC capabilities were evaluated. Results A total of 116 employees participated in using the system. The system performance evaluation indicated that functionality (3.78 ± 0.68), practicality (4.02 ± 0.74), reliability (3.45 ± 0.50), efficiency (4.14 ± 0.69), accuracy (3.36 ± 0.58), and assessability (3.05 ± 0.47) met basic levels (> 3), with efficiency improvement and practicality achieving a good level (> 4). After 12 months of training and study based on the system, the participants demonstrated improved emergency knowledge (χ2 = 37.69, p

Abstract Background The intracellular bacterium Listeria monocytogenes is an attractive vector for cancer immunotherapy as it can effectively deliver tumor antigens to antigen-presenting cells, leading to a robust antitumor response. Results In this study, we developed a novel vaccine platform called Listeria-based Live Attenuated Double Substitution (LADS), which involves introducing two amino acid substitutions (N478AV479A) into the virulence factor listeriolysin O (LLO). LADS is a safe vaccine platform, with an attenuation of nearly 7000-fold, while retaining complete immunogenicity due to the absence of deletion of any virulence factors. We developed two LADS-based vaccines, LADS-E7 and LADS-AH1, which deliver the human papillomavirus (HPV) type 16 E7 oncoprotein and murine colon carcinoma immunodominant antigen AH1, respectively. Treatment with LADS-E7 or LADS-AH1 significantly inhibited and regressed established tumors, while also dramatically increasing the populations of tumor-infiltrated antigen-specific CD8+ T cells. RNA-sequencing analysis of tumor tissue samples revealed that LADS-E7 altered the expression of genes related to the immune response. Moreover, intratumoral injection of LADS-based vaccines induced strong antitumor responses, generating systemic antitumor responses to control distant tumor growth. Encouragingly, LADS-E7 or LADS-AH1 immunization effectively prevented tumor formation and growth. Conclusions Our findings demonstrate that LADS-based vaccines represent a more powerful platform for the development of immunotherapeutic and preventive vaccines against cancers and infectious diseases.

Abstract Gastric cancer (GC) remains a significant global health challenge due to its high morbidity and mortality rates. The development of GC is a multi-hit process and the exploration of precancerous lesions is crucial. To elucidate the molecular and cellular dynamics underlying gastric carcinogenesis, we conducted an integrative single-cell RNA sequencing analysis of 26,028 high-quality cells from gastric antral mucosa biopsies across various stages, including non-atrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, and early gastric cancer. By constructing a detailed single-cell atlas, we identified distinct epithelial cell subpopulations and their corresponding molecular signatures. We focused on the biological link between gastric epithelial cells and cancer cells. Notably, we observed that gland mucous cells acquired an intestinal-like stem cell phenotype during metaplasia, with MUC6, MUC2 and OLFM4 emerging as the specific markers for unique endocrine cells in early malignant lesions. Additionally, our analysis highlighted UPP1 as a key oncogene, with its expression progressively increasing from normal epithelial cells to malignant cells. UPP1 upregulation was shown to promote GC cell proliferation and migration, implicating it in the oncogenic process. Further, we explored the impact of Helicobacter pylori infection on gene expression, revealing that Helicobacter pylori infection upregulates UPP1 via the NF-κB pathway. Our cell-cell communication analysis underscored the significant role of the Macrophage migration inhibitory factor pathway in the tumor microenvironment, contributing to GC progression. Various key molecules involved in intestinal metaplasia, along with UPP1 and the Macrophage migration inhibitory factor pathway, collectively illustrate the multifaceted nature and complexity of gastric cancer evolution, highlighting the cumulative impacts that drive tumorigenesis.

There is an urgent demand for the development of new resource-saving and high-efficiency cryogenic refrigeration technologies against the historical backdrop of increasing scarcity of resources and energy. Magnetic refrigeration technology based on the magnetocaloric effect (MCE) of magnetic materials is a promising approach to address helium resource constraints and improve energy efficiency. Here, a brilliant cryogenic magnetic refrigerant with a large low-field MCE and excellent refrigeration performance is presented. Benefiting from the enhanced ferromagnetism and low saturation magnetic field, the peaks of magnetic entropy change, refrigeration capacity, and adiabatic temperature change of Eu(Ti,Nb,Zr)O3 compounds reach 19.6 J·kg−1·K−1, 87.6 J·kg−1, and 5.5 K, respectively, for a field change of 0−1 T. Magnetic refrigeration experiments on a Gifford‒McMahon (GM)/magnetic hybrid refrigerator further demonstrated that EuTi0.8375Nb0.0625Zr0.1O3 is an excellent magnetic refrigerant operating near the liquid helium temperature. An appropriate amount of this magnetic refrigerant can significantly improve the refrigeration performance of the hybrid refrigerator. The cooling power in hybrid refrigeration mode is improved by a maximum of 52% over that in pure GM/HoCu2 mode at 4.2 K and 0.5 Hz. In addition, the cooling efficiency at 4.2 K is more than 40% greater than that of the pure GM/HoCu2 refrigerator.

Abstract Multiple sclerosis (MS) is a severe brain disease that permanently destroys brain cells, impacting vision, balance, muscle control, and daily activity. This research employs a weighted combination of deep neural networks and optimization techniques for MS disease diagnosis. This method uses slices of magnetic resonance imaging (MRI) images as input. Then, after the pre-processing operation, the process of segmentation and identification of the region of interest (ROI) is performed using a combination of the fuzzy c-means (FCM) algorithm and the capuchin search algorithm (CapSA) algorithm. When the target view is detected, the features of each ROI are extracted through three techniques: local binary pattern (LBP), multi-linear principal component analysis (MPCA), and gray level co-occurrence matrix (GLCM). Each of these features is then processed by a deep neural network. In each deep neural network, the CapSA algorithm is used to determine the optimal topology structure and adjust the weight vector of the neural network. This means that in this process, the vector and topology of the deep neural network are adjusted using the CapSA algorithm in such a way that the training error is minimized. Finally, after creating the trained models, the weighted combination of the outputs of these three models is used for the final diagnosis. The implementation results showed that our method was successful in achieving 100% precision compared to other comparative methods. Also, in the average accuracy criterion, it showed a performance of 99.51%, which shows the high performance of our method in diagnosing patients.

Dynamic analysis of the tethered satellite system (TSS) can provide a fundamental guideline to the evaluation of performance and robust design of the system examined. Uncertainties inherited with the parameters would induce unexpected variation of the response and deteriorate the reliability of the system. In this work, the effect of uncertain mass of the satellites on the deployment and retrieval dynamics of the TSS is investigated. First the interval mode is employed to take the variation of mass of satellite into account in the processes of deployment and retrieval. Then, the Chebyshev interval method is used to obtain the lower and upper response bounds of the TSS. To achieve a smooth and reliable implementation of deployment and retrieval, the nonlinear programming based on the Gauss pseudo-spectral method is adopted to obtain optimal trajectory of tether velocity. Numerical results show that the uncertainties of mass of the satellites have a distinct influence on the response of tether tension in the processes of deployment and retrieval.

The application of machine learning techniques in biological research, especially when dealing with limited data availability, poses significant challenges. In this study, we leveraged advancements in method development for predicting protein-protein binding strength to conduct a systematic investigation into the application of machine learning on limited data. The binding strength, quantitatively measured as binding affinity, is vital for understanding the processes of recognition, association, and dysfunction that occur within protein complexes. By incorporating transfer learning, integrating domain knowledge, and employing both deep learning and traditional machine learning algorithms, we mitigated the impact of data limitations and made significant advancements in predicting protein-protein binding affinity. In particular, we developed over 20 models, ultimately selecting three representative best-performing ones that belong to distinct categories. The first model is structure-based, consisting of a random forest regression and thirteen handcrafted features. The second model is sequence-based, employing an architecture that combines transferred embedding features with a multilayer perceptron. Finally, we created an ensemble model by averaging the predictions of the two aforementioned models. The comparison with other predictors on three independent datasets confirms the significant improvements achieved by our models in predicting protein-protein binding affinity. The programs for running these three models are available at https://github.com/minghuilab/BindPPI.

The genus Grouvellinus Champion, 1923 comprises 60 described species distributed across the Oriental and Palearctic regions. Species diversity is very high in mainland China, with 28 recorded species. Here, the results of the aquatic beetle survey in Guizhou Province are presented; they began in 2021, when we collected more than 5000 specimens of riffle beetle. All specimens come from small ravine streams where inhabited submerged stones. Using morphological characters of adults such as body form and size, coloration, elytral, pronotal and ventral surface structures, and forms of male and female genitalia, five new species were discovered and are described: Grouvellinus loong sp. nov., G. buyi sp. nov., G. wangmoensis sp. nov., G. lihaitaoi sp. nov., G. muyinlini sp. nov. The species descriptions contain illustrations of diagnostic characters and measurements of metric characters such as body length, pronotal length, pronotal width, elytral length and width, and head length and width. The females are, on average, larger and have only slight differences in external morphology compared to the males. The comparative diagnoses discuss characters of the new and already known species. The results show that the existing species diversity requires more detailed research focusing on larger areas of South China in the future.

Heterostructured design and microcrack management mitigate the strength-ductility dilemma in metallic materials. Here, we demonstrate a simultaneous enhancement of strength and ductility in graphene-decorated bimodal pure nickel, achieving a strength increase to 1 GPa and an 18% improvement in elongation by designing heterostructure with graphene, metal powders, and metal foams. The results show that grain refinement, hetero-deformation-induced hardening, and activated stacking faults mainly cause the strength-ductility synergy. Additionally, while dispersed microcracks nucleate within the fine grain zones, their propagation is constrained by the coarse grain zones. This study provides new insights into improving the strength-ductility combination in metallic materials.

Abstract Background In the context of deeper integration of the internet and healthcare services, eHealth literacy levels have become an important predictor of public health outcomes and health-promoting behaviors. However, there is a lack of comprehensive understanding of eHealth literacy levels among older adults. Objective To systematically assess the level of eHealth literacy among older adults. Methods We conducted searches in MEDLINE, Embase, Web of Science, CINAHL, PsycINFO, China National Knowledge Infrastructure Database (CNKI), Wanfang Database, Weipu Database (VIP), and Chinese Biomedical Database (Sinomed) to collect survey studies on the eHealth literacy levels of the older adults, with a search timeframe from the establishment of the database to May 2024. The quality of the included literature was assessed using the Agency for Healthcare Research and Quality (AHRQ) and the Newcastle-Ottawa Scale (NOS). Additionally, subgroup analysis and meta-regression were conducted to detect sources of heterogeneity. Funnel plots and Egger’s test were used to assess publication bias. Results A total of 48 relevant studies were included, including 45 cross-sectional, 2 cohort studies and 1 longitudinal study, comprising 33,919 older adults. The quality of the studies was all above moderate, with 10 high-quality publications. Meta-integration results showed that the eHealth literacy score of older adults was 21.45 (95% CI:19.81–23.08). Subgroup analysis showed that among the elderly population, females had lower eHealth literacy at 19.13 (95% CI:15.83–22.42), those aged 80 years and older had lower eHealth literacy at 16.55 (95% CI:11.73–21.38), and elderly individuals without a spouse and living alone had even lower eHealth literacy at 18.88 (95% CI:15.71–22.04) and 16.03 (95% CI:16.51–21.79). Based on region, eHealth literacy was lower among older adults in developing countries at 20.71 (95% CI:18.95–22.48). Meta-regression results indicate that sample size and region can significantly impact heterogeneity. Conclusion Our results found that the average eHealth literacy score of the elderly was 21.45, which was much lower than the passing level (≥ 32), suggesting that more attention should be paid to the eHealth literacy aspect of the elderly. Meanwhile, due to the limitation of the literature sources, the global representativeness of the results of this study still needs to be supported by more research data from other countries.

Abstract Background Phosphorus (P) plays a vital role in plant growth. The pqqC and phoD genes serve as molecular markers for inorganic and organic P breakdown, respectively. However, the understanding of how P-mobilizing bacteria in soil respond to long-term fertilization and rhizobium application is limited. Herein, soil that had been treated with fertilizer and rhizobium for 10 years was collected to investigate the characteristics of P-mobilizing bacterial communities. Five treatments were included: no fertilization (CK), phosphorus fertilizer (P), urea + potassium fertilizer (NK), NPK, and PK + Bradyrhizobium japonicum 5821 (PK + R). Results The soybean nodule dry weight was highest in the P treatment (1.93 g), while the soybean yield peaked in the PK + R treatment (3025.33 kg ha− 1). The abundance of the pqqC gene increased in the rhizosphere soil at the flowering-podding stage and in the bulk soil at the maturity stage under the P treatment, while its abundance increased in the bulk soil at the flowering-podding stage and in the rhizosphere soil at the maturity stage under the PK + R treatment. The abundance of the phoD gene was enhanced in the bulk soil at the flowering-podding stage under the PK + R treatment. The Shannon and Ace indexes of pqqC- and phoD-harboring bacteria were higher in the rhizosphere soil at maturity under the PK + R treatment compared to other treatments. Furthermore, a comprehensive analysis of the neutral community model and co-occurrence pattern demonstrated that the application of P fertilizer alone led to an increase in the distribution and dynamic movement of pqqC-harboring bacteria, but resulted in a decrease in complexity of network structure. On the other hand, rhizobium inoculation enhanced the distribution and dynamic movement of phoD-harboring bacteria, as well as the stability and complexity of the network structure. Pseudomonas and Nitrobacter, as well as Steptomyces, Stella, and Nonomuraea, may be crucial genera regulating the composition and function of pqqC- and phoD-harboring communities, respectively. Conclusions These findings affirm the crucial role of fertilization and rhizobium inoculation in regulating pqqC- and phoD-harboring bacterial communities, and highlight the significance of long-term phosphate-only fertilization and rhizobium inoculation in enhancing dissolved inorganic phosphorus and mineralized organophosphorus, respectively.

The rapid development of informatization and digitalization in public security business has generated a large amount of law enforcement case data in public security work. However, due to various types of text and large amount of information, front-line police officers often face problems such as low reading efficiency and difficulty in aggregating information in the process of reading case files. In order to further utilize the law enforcement case text, it is necessary to conduct intelligent analysis and knowledge extraction. However, due to the professionalism, data sensitivity, confidentiality of public security professional law enforcement case text, as well as the requirements of public security data going out of the network, only a small number of learning training samples can be obtained, and the traditional deep learning model has unsatisfactory extraction effect. Therefore, this paper proposes to build a large language model in vertical fields with fewer resources and data, and realize the adaptation of the model to the public security profession. The model uses knowledge editing technology MEMIT (mess-editing memory in a transformer), low-resource fine-tuning technology LoRA (low-rank adaptation), and prompt templates to improve the model??s understanding of public security knowledge such as police terminology and common sense. Moreover, in order to further improve the knowledge extraction effect of the model, a small sample law enforcement case text data extraction process is designed to better integrate the professional knowledge related to the case in the model. Experimental results show that the accuracy of the public security professional vertical field large language model integrated with the extraction process in various knowledge extraction tasks is significantly improved compared with the traditional methods, which helps front-line police officers quickly, objectively and accurately analyze law enforcement case text, dig out potential case information, and support the intelligent development of public security work.

Abstract Inflammation plays a crucial role in cancer development. The neutrophil-to-lymphocyte ratio (NLR), a measure of inflammation, is obtained from a complete blood count. However, little is known about the association between NLR and cancer in the general adult population in the United States. This study aimed to evaluate whether NLR is associated with cancer in American adults. This retrospective cross-sectional study included 28,016 adult participants from the National Health and Nutrition Examination Survey (NHANES) dataset spanning 2005 to 2018. Data on demographics (age, sex, race, marital status, Poverty-Income Ratio, education level), lifestyle factors (smoking, alcohol consumption, body mass index), medical conditions (hypertension, diabetes, cardiovascular disease), and laboratory parameters (hemoglobin, platelet count, alanine aminotransferase, creatinine, albumin, and lactate dehydrogenase), were collected. Logistic regression analysis was used to investigate the research objectives. Of the total 28,016 participants, 2639 had cancer. The mean age was 49.6 ± 17.6 years, and 50% were male. A positive association between NLR and cancer risk was observed after multivariate adjustment (OR = 1.20, 95% confidence interval (CI) = 1.05–1.36, p = 0.006). Similar patterns were observed in subgroup analyses (all p-values for interaction > 0.05). A higher NLR was directly correlated with an increased risk of developing cancer in adults.

Abstract Coherent dispersive wave emission, as an important phenomenon of soliton dynamics, manifests itself in multiple platforms of nonlinear optics from fibre waveguides to integrated photonics. Limited by its resonance nature, efficient generation of coherent dispersive wave with ultra-broad bandwidth has, however, proved difficult to realize. Here, we unveil a new regime of soliton dynamics in which the dispersive wave emission process strongly couples with the splitting dynamics of the driving pulse. High-order dispersion and self-steepening effects, accumulated over soliton self-compression, break the system symmetry, giving rise to high-efficiency generation of coherent dispersive wave in the ultraviolet region. Simultaneously, asymmetric soliton splitting results in the appearance of a temporally-delayed ultrashort pulse with high intensity, overlapping and copropagating with the dispersive wave pulse. Intense cross-phase modulations lead to octave-wide broadening of the dispersive wave spectrum, covering 200–400 nm wavelengths. The highly-coherent, octave-wide ultraviolet spectrum, generated from the simple capillary fibre set-up, is in great demand for time-resolved spectroscopy, ultrafast electron microscopy and frequency metrology applications, and the critical role of the secondary pulse in this process reveals some new opportunities for all-optical control of versatile soliton dynamics.

Abstract Prostate cancer is one of the most common cancers in men and poses a significant threat to global male health. Traditional prostate cancer assessment methods have certain limitations, necessitating the identification of new prognostic factors and treatment targets. Our study revealed that low expression of the cornichon family AMPA receptor auxiliary protein 2 (CNIH2) gene was associated with a better progression-free survival rate in prostate cancer patients. The area under the receiver operating characteristic (ROC) curve (AUC) showed that the prognostic ability of the CNIH2 gene was high at 1, 3, and 5 years. The gene was an independent prognostic factor according to multivariate analysis. Functional verification experiments showed that knocking down the CNIH2 gene could inhibit the proliferation, migration and invasion of prostate cancer cells and could also inhibit tumor growth in nude mice. Our study is the first to reveal the important role of the CNIH2 gene in prostate cancer. This discovery provides a new research direction for individualized treatment and prognostic evaluation of prostate cancer.

Abstract Low-cost and green preparation of efficient sorbents is critical to the removal of organic contaminants during water treatment. In this study, the co-pyrolysis of macroalgae and oyster shell was designed to synthesize nitrogen-doped porous biochars for sorption removal of atrazine from water. Oyster shell played a significant role in opening pores in macroalgae-derived biochars, resulting in the surface area of the macroalgae (Enteromorpha prolifera and Ulva lactuca) and oyster shell co-pyrolyzed carbonaceous as high as 1501.80 m2 g−1 and 1067.18 m2 g−1, the pore volume reached 1.04 cm3 g−1 and 0.93 cm3 g−1, and O/C decreased to 0.09 and 0.08, respectively. The sorption capacity of atrazine to nitrogen-doped porous biochars (the Enteromorpha prolifera, Ulva lactuca and oyster shell co-pyrolyzed carbonaceous) reached 312.06 mg g−1 and 340.52 mg g−1. Pore-filling, hydrogen bonding, π-π or p-π stacking and electrostatic interaction dominated the multilayer sorption process. Moreover, the nitrogen-doped porous biochars showed great performance in cyclic reusability, and the Enteromorpha prolifera, Ulva lactuca and oyster shell co-pyrolyzed carbonaceous sorption capacity still reached 246.13 mg g−1 and 255.97 mg g−1, respectively. Thus, this study suggested that it is feasible and efficient to remove organic contaminants with the nitrogen-doped porous biochars co-pyrolyzed from macroalgae and oyster shell, providing a potential green resource utilization of aquatic wastes for environmental remediation. Graphical Abstract

Abstract This study aimed to design a VEGFR-targeting peptide–drug conjugate with the ability to decrease tumor burden and suppress tumor angiogenesis, and to further evaluate the therapeutic effect of anti-PD-1 antibody in HCC therapy. A VEGFR-targeting peptide VEGF125 − 136 (QR) was conjugated with a lytic peptide (KLU) to form a peptide–drug conjugate QR-KLU. And the efficacy of QR-KLU in combination with anti-PD-1 antibody for HCC therapy in vivo and in vitro were evaluated. QR-KLU inhibited the proliferation and migration of mouse HCC cell line (Hepa1–6) cells under normoxic and hypoxic conditions in a dose-dependent manner. In the subcutaneous Hepa1–6 tumor model, QR-KLU combined with the anti-PD-1 antibody substantially inhibited tumor growth, promoted tumor necrosis, and prolonged the survival time of tumor-bearing mice. QR-KLU substantially inhibited hypoxia-induced expression of VEGF, promoted tumor vascular normalization, and increased cluster of differentiation 8+ (CD8+) T cell infiltration in the tumor. In addition, QR-KLU and anti-PD-1 antibody demonstrated a strong synergistic effect in promoting the activation of intratumoral CD8+ T cells, reducing the expression of immune-inhibitory factors, and increasing the expression of immune-stimulatory factors. This study proposed a novel approach for enhancing the efficacy of anti-PD-1 antibody using a VEGFR-targeting peptide–drug conjugate in HCC therapy.

Abstract The effects of stochastic volatility, jump clustering, and regime switching are considered when pricing variance swaps. This study established a two-stage procedure that simplifies the derivation by first isolating the regime switching from other stochastic sources. Based on this, a novel probabilistic approach was employed, leading to pricing formulas with time-dependent and regime-switching parameters. The formulated solutions were easy to implement and differed from most existing results of variance swap pricing, where Fourier inversion or fast Fourier transform must be performed to obtain the final results, since they are completely analytical without involving integrations. The numerical results indicate that jump clustering and regime switching have a significant influence on variance swap prices.

Abstract Background Helicobacter pylori (H. pylori) infection is critical in the development and occurrence of gastric cancer. H. pylori secretes gamma-glutamyl transferase (GGT), which affects energy metabolism and histone methylation in mesenchymal stem cells. However, its effect on human gastric epithelial cells remains unclear. This study aimed to investigate the effects of GGT on energy metabolism and histone methylation in gastric epithelial cells and determine its role in the development and progression of H. pylori-induced gastric cancer. Methods A GGT knockout H. pylori strain and mouse gastric cancer model were constructed, and alpha-ketoglutarate (α-KG) was added. The underlying mechanism was investigated using proteomics, immunohistochemistry, Western blotting, and other experimental assays. Results H. pylori can colonize the host’s stomach and destroy the gastric epithelium. GGT secreted by H. pylori decreased the concentration of glutamine in the stomach and increased H3K9me3 and H3K27me3 expression, which promoted the proliferation and migration of gastric epithelial cells. Additionally, α-KG reversed this effect. GGT increased the tumorigenic ability of nude mice. GGT, secreted by H. pylori, promoted the expression of ribosomal protein L15 (RPL15), while GGT knockout and supplementation with α-KG and trimethylation inhibitors reduced RPL15 expression and Wnt signaling pathway expression. Conclusions H. pylori secreted GGT decreased the expression of glutamine and α-KG in gastric epithelial cells, increased the expression of histones H3K9me3 and H3K27me3, and activated the Wnt signaling pathway through RPL15 expression, ultimately changing the biological characteristics of the gastric epithelium and promoting the occurrence of gastric cancer. Altered energy metabolism and histone hypermethylation are important factors involved in this process. Graphical abstract

ObjectiveTo understand the pneumococcal vaccination status and its influencing factors among young and middle-aged populations, and provide reference for promoting pneumococcal vaccination. MethodsFrom May to August 2023, a multi-stage random cluster sampling method was used to select 5 928 residents aged 19 – 59 years old from Nanchang city in Jiangxi province, Changsha city in Hunan province, and Kunming city in Yunnan province for an online questionnaire survey on pneumococcal vaccination status. ResultsAmong the 4 895 young and middle-aged people finally included in the analysis, only 833 had received pneumococcal vaccine in the past 5 years, with a pneumococcal vaccine uptake rate of 17.02%; multivariate unconditional logistic regression analysis showed that the pneumococcal vaccine uptake rates were higher among those aged 45 – 59 years old, agriculture, forestry, animal husbandry and fishery production personnel, professional and technical personnel, smokers, those with general knowledge of pneumococcal diseases and vaccines, and those with general and good trust in pneumococcal vaccines, while the uptake rates were lower among those with high school/technical secondary school education or above and office clerks and related personnel; the top three reasons for pneumococcal vaccination among young and middle-aged people were disease prevention (75.87%), protecting family and colleagues (57.38%), and government and health administration recommending vaccination (43.22%), while the top three reasons for not receiving pneumococcal vaccine were worrying about adverse reactions after vaccination (42.22%), no time for vaccination (28.19%), and believing that the vaccine had limited effectiveness (25.11%), and the top three factors most likely to change vaccination willingness were free/discounted vaccines (46.63%), worrying about the impact of pneumonia infection on family and colleagues (46.53%), and government and health administration recommending vaccination (45.89%). ConclusionThe pneumococcal vaccine uptake rate among young and middle-aged populations was low, and age, education level, occupation, smoking status, knowledge of pneumococcal diseases and vaccines, and trust in vaccines was the main influencing factors for pneumococcal vaccination in this population. Comprehensive policy measures, especially the introduction of preferential policies related to pneumococcal vaccines, should be adopted to promote vaccination.

Purpose: The purpose of this study is to reveal the influence mechanism of social innovation education (SIE) on sustainability learning outcomes and analyze the roles of intrinsic learning motivation and prosocial motivation. Design/methodology/approach: A sample of 322 undergraduates from one higher education institution in Tianjin was used to test the hypotheses. Findings: This study found that SIE positively affected sustainability learning outcomes, and intrinsic learning motivation mediated the relationship between them. The results showed that prosocial motivation positively moderates the positive effect of SIE on intrinsic learning motivation and the overall mediation model. Practical implications: The findings have important practical implications for higher education institutions to carry out SIE. Higher education institutions should focus on integrating social innovation and sustainability into top-level design. Furthermore, higher education institutions should focus on stimulating students' intrinsic learning motivation and cultivating their prosocial motivation. Originality/value: This study identified the relationship between SIE and sustainability learning outcomes and clarified the influence mechanism of SIE on sustainability learning outcomes. Moreover, this study emphasized the importance of prosocial motivation as a key boundary condition of SIE.

The age at which people acquire a word influences word recognition, known as the age of acquisition (AoA) effect. In the first language (L1), AoA effects are widely found in various languages and experimental tasks. Arbitrary Mapping Hypothesis proposes that AoA effects reflect the loss of network plasticity during the learning of mappings between input and output representations. It predicts that the AoA effect appears (or is larger) when the input-output mapping is arbitrary/inconsistent, relative to consistent input-output mapping. The present study examined how these predictions generalised to the second language (L2). We explored whether the L2 AoA effect was modulated by spelling-sound consistency in Chinese-English bilinguals, adopting a delayed word naming task. The results showed that the mapping consistency modulated the L2 AoA effect on the N170, P200 and N400 components. L2 AoA effect was insignificant in the consistent condition but was significant in the inconsistent condition: late-acquired words elicited larger N170, smaller P200, and larger N400 compared to early-acquired words. These findings suggest that L2 AoA effects occur in the spelling-sound connections, providing direct evidence for the Arbitrary Mapping Hypothesis.

Achieving the dual carbon goals requires profound systemic transformations across the economy and society. Accurately characterizing the spatial correlation network features and mechanisms of carbon emission efficiency (CEE) is critical for promoting regionally coordinated development. This study analyzes 16 prefecture-level cities in Shandong Province, China, from 2006 to 2021, using the Super-SBM model to measure urban CEE. A modified gravity model and social network analysis were combined to explore the spatial network structure, while the Logarithmic Mean Divisia Index and Quadratic Assignment Procedure models investigated its formation mechanisms. The results show that Shandong’s overall CEE has improved but remains spatially imbalanced, characterized by a persistent “higher in the east, lower in the west” pattern. Key cities, such as Jinan and Qingdao, emerge as central nodes in an evolving multi-polarized spatial network, exerting strong influence. Network density has increased over time, enhancing inter-city collaboration in emission reduction. Among driving factors, technological innovation significantly reduces emissions, though economic growth plays a stronger role in shaping network connections. Geographic adjacency further reinforces spatial correlations. While Shandong’s CEE has shown steady progress, targeted efforts in carbon management and technological advancements for less efficient cities are crucial for achieving collaborative emission reduction across the province.

Prostate cancer (PCa) is a common and serious health issue among older men globally. Metabolic reprogramming, particularly involving lactate and mitochondria, plays a key role in PCa progression, but studies linking these factors to prognosis are limited. To identify novel prognostic markers of PCa based on lactate-mitochondria-related genes (LMRGs), RNA sequencing data and clinical information of PCa from The Cancer Genome Atlas (TCGA) and the cBioPortal database were used to construct a lactate-mitochondria-related risk signature. Here, we established a novel nine-LMRG risk signature for PCa, and Kaplan-Meier curves confirmed a worse prognosis for high-risk subgroups in the TCGA dataset. Meanwhile, a nomogram that effectively predicts the prognosis of PCa patients was also constructed. Next, close associations between the lactate-mitochondria-related signature and the immune microenvironment were examined to clarify the role of LMRGs in shaping the immune landscape. Furthermore, as the only lactate-related gene among the nine key prognostic risk genes, myeloperoxidase (MPO) was identified as a key factor that mediates lactate production in vitro and in vivo through attenuation of the glycolytic pathway. More importantly, MPO significantly inhibited PCa cell migration, invasion, and epithelial–mesenchymal transition (EMT), indicating its potential as an anticancer gene. Additionally, PCa with high MPO expression is highly sensitive to chemotherapeutic agents and mitochondrial inhibitors, highlighting its potential as an improved therapeutic strategy for PCa management.

Abstract The major histocompatibility complex class I (MHCI) trafficking signal (MITD) plays a pivotal role in enhancing the efficacy of mRNA vaccines. However, there was a lack of research investigating its efficacy in enhancing immune responses to RNA virus infections. Here, we have developed an innovative strategy for the formulation of mRNA vaccines. This approach involved the integration of MITD into the mRNA sequence encoding the virus antigen. Mechanistically, MITD‐based mRNA vaccines can strengthen immune protection by mimicking the dynamic trafficking properties of MHCI molecule and thus expand the memory specific B and T cells. The model MITD‐based mRNA vaccines encoding binding receptor‐binding domain (RBD) of SARS‐CoV‐2 were indeed found to achieve protective duration, optimal storage stability, broad efficacy, and high safety.

Growing evidence suggests that the use of manure containing residual antibiotics universally leads to an increase in soil antibiotic resistance genes (ARGs). However, there is limited understanding of the influence of long-term antibiotic-free fertilization and the differences between antibiotic-free manure and chemical fertilizer on soil ARGs. This study aimed to quantify the assembly patterns of the antibiotic resistome by in situ probing bacterial community and environmental variations in field soils that have been subjected to long-term exposure to chemical fertilizer and/or manure from animals without antibiotic amendments. Long-term fertilization slightly impacts the diversity of antibiotic resistomes, with 85.5 % of total ARGs and mobile genetic elements (MGEs) being common across all treatment types, while significantly increasing their abundances from 0.68 to a maximum of 0.90 copies/16S rRNA. The rise in ARG abundances was less pronounced when using antibiotic-free manure compared to chemical fertilizer, particularly for Rank Ⅱ ARGs. However, when antibiotic-free manure and chemical fertilizer were combined, a significant increase in nutrients (such as available nitrogen and organic matter) and MGEs occurred, leading to the enrichment of soil microbial populations, especially in certain resistant species, and Rank Ⅰ and Ⅱ ARGs. Despite the influence of various factors like bacterial communities, soil properties, heavy metals, and MGEs, the MGEs had the most significant standardized effects on shaping ARGs through both direct and indirect pathways. Our findings indicates that while of antibiotic-free manure can lower the risk of antibiotic residues and promote sustainable farming practices, it may not fully eliminate the prevalence of ARGs, highlighting the need for more comprehensive strategies to address antibiotic resistance in agriculture rather than simply prohibiting the use of antibiotics.

Objective To assess the effect of sodium-glucose cotransporter 2 inhibitors (SGLT2-I) on cardiac remodeling and prognosis in type 2 diabetes mellitus (T2DM) patients presenting with acute myocardial infarction (AMI). Methods In this single-center retrospective active-comparator study, consecutive diabetic AMI patients undergoing percutaneous coronary intervention (PCI) between 2021 and 2023 were enrolled. Patients were divided into SGLT2-I users and non-SGLT2-I users based on discharge medications. The primary endpoint was the left ventricular remodeling index (LVRI), defined as the relative change in LV end-diastolic volume after six months. The secondary outcomes included major adverse cardiovascular events (MACE), comprising all-cause mortality, hospitalization for heart failure, nonfatal MI, and nonfatal stroke. Results The study comprised 423 T2DM AMI patients(with or without ST-segment elevation), with 239 SGLT2-I users and 184 non-SGLT2-I users. At six months, LVRI was significantly lower in the SGLT2-I users compared to the non-SGLT2-I users (3.49 ± 19.71 vs 7.06 ± 15.15, P = .042). The non-SGLT2-I users exhibited a higher prevalence of positive LVR (LVRI > 0%) (64.67% vs 50.63%, P = .004) and pathological LVR (LVRI > 20%) (19.57% vs 12.13%, P = .036). Multivariate logistic regression indicated that SGLT2-I was associated with a reduced risk of LVR (OR 0.6; 95%CI 0.38-0.97; P = .035). During a mean follow-up of 25 ± 8 months, Kaplan-Meier analysis demonstrated a lower rate of MACE-free survival in the non-SGLT2-I users ( P = .005). Conclusions SGLT2-I protects against LVR and lowers the risk of adverse cardiovascular outcomes in T2DM AMI patients.

RAS-selective lethal small molecule 3 (RSL3) is a small-molecule compound that triggers ferroptosis by inactivating glutathione peroxidase 4. However, its effect on the radioresistance of glioma cells and the underlying mechanisms remains unclear. In this study, we found that RSL3 sensitized glioma cells to ionizing radiation (IR) and enhanced IR-induced DNA double-strand breaks (DSBs). Inhibition of ferroptosis pathways partly prevented the clonogenic death caused by the IR/RSL3 combination but did not alleviate the DNA DSBs, indicating that RSL3 promotes IR-induced DNA DSBs via a non-ferroptotic mechanism. We demonstrated that transglutaminase 2 (TGM2) plays a vital role in the radiosensitization effect of RSL3 on glioma cells. Treatment with RSL3 downregulated TGM2 in a dose-dependent manner. Overexpression of TGM2 not only alleviated DNA DSBs but also inhibited clonogenic death caused by the IR/RSL3 combination. Mechanistically, RSL3 triggered oxidative stress in glioma cells, which promoted the S-gluthathionylation of TGM2 via upregulation of glutathione S-transferase P1(GSTP1), culminating in the proteasomal degradation of TGM2. This process resulted in the suppression of DNA repair mechanisms by impeding the nuclear accumulation of TGM2 and disrupting the interaction between TGM2 and topoisomerase IIα after irradiation. We also found that RSL3 inhibited glioma cell epithelial-mesenchymal transition (EMT) in both IR-treated and non-IR-treated cells. Overexpression of TGM2 prevented, while knockdown of TGM2 aggravated the EMT inhibition caused by RSL3, indicating that RSL3 also sensitized glioma cells to IR by inhibiting EMT via a TGM2-dependent mechanism. Furthermore, in mice bearing human U87 tumor xenografts, RSL3 administration synergized with IR to inhibit tumor growth, accompanied by TGM2 inhibition, DNA DSBs, and EMT inhibition in tumor tissues. Taken together, we demonstrated that RSL3 sensitizes glioma cells to IR by suppressing TGM2-mediated DNA repair and EMT.

Starch has been recognized as a vital ingredient in surimi products due to its ability to absorb water, which reduces the deterioration of gels and water loss during freezing and thawing. However, it is essential to ascertain the role of starch in the formation of ice crystals and the texture of surimi gels. The impact of freeze-thaw cycles on the morphology and distribution of ice crystals, as well as the textural characteristics of gelatinized and ungelatinized starch-surimi gels was investigated. The results of light microscopy revealed that the presence of starch, irrespective of whether it was gelatinized, resulted in a reduction in the size of ice crystals within the surimi gel network during the freeze-thaw process. In addition, starch in surimi gels was subjected to freeze-thaw cycles, resulting in the emergence of two distinct states of bound water (0.1–1 ms and 1–10 ms). The higher relative content of immobile water indicated that the gelatinized starch had improved water holding properties. Furthermore, the incorporation of gelatinized starch into surimi enhanced its freeze-thaw stability and retarded the loss of gel strength, hardness, and whiteness. The addition of starch had a synergistic impact, enhancing the gel properties by affecting the formation of ice crystals and water absorption.

The selection of structural strength indicators is of utmost importance for slope engineering safety. This paper, with the backdrop of the destruction of high liquid limit clay layers in the Huai River slope, aims to investigate the influence of dry-wet (D-W) cycles on the structural and mechanical properties of undisturbed high liquid limit clay. Through unconfined compression tests, scanning electron microscopy (SEM) tests, and triaxial shear tests, the structural behavior, stress-strain curves, porewater pressure-strain curves, and effective stress paths of undisturbed samples taken at three different angles and reconstituted samples were analyzed under the condition of maximum drying stress with 0 and 1 D-W cycle. Based on the impact of D-W cycles on the effective stress path, the shear failure mode of structurally high liquid limit clay under the influence of D-W cycles was identified. A method for evaluating the anisotropic level of structural clay after experiencing D-W cycles was proposed. The test results show that compared with reconstructed soil, the undisturbed high liquid limit clay with structure is more significantly affected by the D-W cycle. After D-W cycles, the CU shear strength of high liquid limit clay increased significantly. The failure mode transitioned from a hardening-shear dilation mode to a softening-partial shear contraction-partial shear dilation mode. The appearance of the phase transition state (PTS) point may be attributed to the partial action of effective stress on cracks inside the sample, resulting in shear contraction. D-W cycles weakened the structural properties (anisotropy) of high liquid limit clay.

IntroductionTraditional Chinese Medicine (TCM), specifically Gui-Shen-Wan, has shown promise in restoring ovarian function among reproductive-age women who had impaired ovarian functions, yet the underlying mechanisms remain elusive. Recent studies highlight the pivotal role of the gut microbiome (GM) in mediating the therapeutic effects of TCM. However, it is unclear whether the GM contributes to Gui-Shen-Wan’s therapeutic restoration of ovarian functions.MethodsThis study employed a mouse model with cyclophosphamide-induced decreased ovarian function (P_T and P_AT groups) and a control group without modeling. The P_AT group received a 7-day course of oral antibiotics to deplete the GM prior to a 20-day Gui-Shen-Wan treatment regimen.ResultsBoth P_T and P_AT mice exhibited prolonged metestrus/diestrus phases compared to controls (p

BackgroundCurrent lines of evidence indicate that cysteine-rich secretory protein 3 (CRISP3) is an immunoregulatory factor. Nevertheless, no study has explored the relationships between the values of CRISP3 and sepsis.MethodsWe conducted a comprehensive literature search and meta-analysis from the Gene Expression Omnibus (GEO) and ArrayExpress to determine the expression of CRISP3 in sepsis patients. Then, we explored whether plasma CRISP3 could serve as a potential biomarker to predict the risk of sepsis via two retrospective trauma cohorts. We evaluated the prediction power using the area under the curve (AUC).ResultsA total of 23 datasets were recruited for the comprehensive meta-analysis, and the combined standardized mean difference (SMD) of CRISP3 was 0.90 (0.50–1.30) (p < 0.001), suggesting that CRISP3 was overexpressed in sepsis patients. Meanwhile, sepsis patients had higher CRISP3 concentrations than non-sepsis patients in 54 trauma patients (p < 0.001). Plasma CRISP3 on admission was significantly associated with the incidence of sepsis [OR = 1.004 (1.002–1.006), p < 0.001]. As a predictive biomarker, CRISP3 obtained a better AUC [0.811 (0.681–0.905)] than C-reactive protein (CRP) [0.605 (0.463–0.735)], procalcitonin (PCT) [0.554 (0.412–0.689)], and Sequential Organ Failure Assessment (SOFA) [0.754 (0.618–0.861)]. Additionally, the clinical relationships between plasma CRISP3 and sepsis were verified in another trauma cohort with 166 patients [OR = 1.002 (1.001–1.003), p < 0.001]. The AUC of CRISP3 was 0.772 (0.701–0.834), which was better than that of CRP [0.521 (0.442–0.599)] and PCT [0.531 (0.452–0.609)], but not SOFA [0.791 (0.717–0.853)].ConclusionOur study indicated and validated that CRISP3 was highly expressed in sepsis. More importantly, CRISP3 may serve as a latent biomarker to predict the risk of sepsis.

ObjectivesLiterature data are scarce on concurrent chemoradiotherapy (CCRT) with S-1 for locally advanced nasopharyngeal carcinoma (LANPC) treatment. This study compared the efficacy and safety of the S-1 versus platinum-based CCRT in LANPC treatment. Methods: This study enrolled 547 patients newly diagnosed with LANPC who underwent CCRT with S-1 or platinum at three institutions. Propensity score matching in a 1:1 ratio balancing baseline features was performed. Survival and adverse effects were compared between groups.ResultsOf 160 patients in the cohort, 100 eligible were propensity score matched. Matched dataset analyses showed a higher 5-year overall survival rate (87.1% vs. 84.7%, P = 0.833), progression-free survival (79.6% vs. 75.5%, P = 0.669), locoregional recurrence-free survival (87.0% vs. 84.7%, P = 0.518), and distant metastasis-free survival (84.8% vs. 83.0%, P = 0.780) in the S-1 group than in the platinum-based CCRT group, although not statistically significant. Objective response rate (98.0% vs. 88.0%, P = 0.117) was significantly higher in the S-1 than in the platinum-based regimen, although it was not statistically reflected. Compared with platinum-based, those undergoing S-1-based chemotherapy demonstrated a higher incidence of grade 3 mucositis (20.0% vs. 2.0%, P = 0.016) in the S-1 group and a lower incidence of leukopenia (44.0% vs. 68.0%, P = 0.033), neutropenia (28.0% vs. 52.0%, P = 0.032), anemia (22.0% vs. 44.0%, P = 0.040), nephrotoxicity (4.0% vs. 20.0%, P = 0.028), and nausea/vomiting (30.0% vs. 56.0%, P = 0.019).ConclusionThe results suggest that S-1 can be used as a concurrent chemotherapy regimen during radiotherapy for patients with LANPC, since it presents a noninferior survival benefit compared with platinum and shows tolerable adverse effects.

Abstract The harmonic compensation of SAPF (shunt active power filter) may trigger harmonic oscillation due to the interaction with grid impedance and non‐linear loads, which distorts the power quality. In previous research, the relevant mechanism has been studied. However, the SAPF generally employs complex harmonic detection algorithm, which significantly increases the computational demands. The SAPF in full compensation mode can effectively solve this problem. But the modification of harmonic detection link may change the oscillation mechanism and previous stabilization methods need to be re‐evaluated. Therefore, this paper establishes the small signal model of the SAPF system in full compensation mode and investigates its oscillation mechanism. It is revealed that harmonic compensation and passive resonance collectively induce the harmonic oscillation. Based on the model, the working mechanism and application performance of the main stabilization methods proposed in the past (harmonic virtual admittance and harmonic compensation canceling) are analyzed and compared. However, neither of them can achieve effective stabilization without sacrificing the performance of compensation. Consequently, the harmonic phase compensation method is proposed to achieve the stabilization of the SAPF system in full compensation mode without affecting normal compensation. Finally, simulations and experiments are performed to verify the mechanism analysis and proposed methods.

Abstract Western criminological literature continues to focus on the binary control system (formal vs. informal), while China has long employed the trinary system (formal, semiformal, and informal) in its construction of social control. China scholars have investigated the prevalence and importance of the trinary control system as a key to understanding social control. However, there is a lack of research on their predictors. The current study aims at investigating the correlates of the prevalence and importance of the observed trinary control system in rural China. Using the sample data of 2343 respondents collected from 164 villages in rural China, the study found that both individual and village factors were the predictors of the prevalence of the observed controls exerted by village committees, a measure of semiformal control, and police, a measure of formal control, in maintaining community social order. Findings included the reported prevalence of four control mechanisms as significant predictors of their importance in community order maintenance. The implications of these findings are discussed.

During the process of electric arc remelting， the content of gas components （such as H， O， N， etc.） in the steel is significantly influenced by the gas permeability of the slag system used. In order to explore a slag system with low hydrogen permeability suitable for nuclear-grade 316H stainless steel in electric arc remelting， the hydrogen permeability of five slag systems used in electric arc remelting was determined. The results showed that the newly developed 63%CaF2-30%Al2O3-7%MgO slag system had the lowest hydrogen permeability.meanwhile the hydrogen permeability of slag system， 65%CaF2-30%Al2O3-5%MgO， was similar to that of the 63%CaF2-30%Al2O3-7%MgO slag system， and hydrogen permeability of both slag systems exhibited a significant reduction compared to the original slag system used in the steel plant's electric arc production，declined from 6.58×10-6 mol/（cm·min） to 1.89×10-6 mol/（cm·min） and 2.18×10-6 mol/（cm·min） respectively.The higher the optical basicity of the slag was， the higher the hydrogen permeability was. CaO in the slag had a high affinity for water and can easily increase the hydrogen content in the steel ingot during electric arc remelting， while the addition of MgO in the slag system can significantly reduce hydrogen permeability. Under the research conditions， the influence of the slag system's constituents on its hydrogen permeability was more significant than the optical basicity.

Abstract. Triggering receptor expressed on myeloid cells-1 (TREM-1) is a member of the immunoglobulin superfamily. As an amplifier of the inflammatory response, TREM-1 is mainly involved in the production of inflammatory mediators and the regulation of cell survival. TREM-1 has been studied in infectious diseases and more recently in non-infectious disorders. More and more studies have shown that TREM-1 plays an important pathogenic role in kidney diseases. There is evidence that TREM-1 can not only be used as a biomarker for diagnosis of disease but also as a potential therapeutic target to guide the development of novel therapeutic agents for kidney disease. This review summarized molecular biology of TREM-1 and its signaling pathways as well as immune response in the progress of acute kidney injury, renal fibrosis, diabetic nephropathy, immune nephropathy, and renal cell carcinoma.

Abstract Background Mobility limitations (e.g., using wheelchair) have been closely linked to diminished functional independence and quality of life in older adults. The regulation of mobility is pertaining to multiple neurophysiologic and sociodemographic factors. We here aimed to characterize the relationships of these factors to the risk of restricted mobility in older adults. Methods In this longitudinal study, 668 older adults with intact mobility at baseline completed the baseline assessments of clinical characteristics, cognitive function, sleep quality, activities of daily living (ADL), walking performance, beat-to-beat blood pressure, and structural MRI of the brain. Then 506 of them (mean age = 70.7 ± 7.5 years) responded to the follow-up interview on the mobility limitation (as defined by if using wheelchair, cane, or walkers, or being disabled and lying on the bed) after 18 ± 3.5 months. Logistic regression analyses were performed to examine the relationships between the baseline characteristics and the follow-up mobility restriction. Results At baseline, compared to intact-mobility group (n = 475), restricted-mobility group (n = 31) were older, with lower score of ADL and the Montreal Cognitive Assessment (MoCA), greater score of Pittsburgh Sleep Quality Index (PSQI), poorer cardio- and cerebral vascular function, and slower walking speeds (ps

The CIR stochastic volatility model is modified to introduce nonlinear mean reversion, with the long-run volatility average as a random variable controlled by two parts being modeled through a Brownian motion and a Markov chain, respectively. This model still possesses an analytical formulation of the forward characteristic function, from which we establish variance swap prices as well as volatility swap ones with a nonlinear payoff in closed form. The numerical implementation of the two formulae demonstrates the significant impact of regime switching.

Abstract Background Cystic Fibrosis causing mutations in the gene CFTR, reduce the activity of the CFTR channel protein, and leads to mucus aggregation, airway obstruction and poor lung function. A role for CFTR in the pathogenesis of other muco-obstructive airway diseases such as Chronic Obstructive Pulmonary Disease (COPD) has been well established. The CFTR modulatory compound, Ivacaftor (VX-770), potentiates channel activity of CFTR and certain CF-causing mutations and has been shown to ameliorate mucus obstruction and improve lung function in people harbouring these CF-causing mutations. A pilot trial of Ivacaftor supported its potential efficacy for the treatment of mucus obstruction in COPD. These findings prompted the search for CFTR potentiators that are more effective in ameliorating cigarette-smoke (CS) induced mucostasis. Methods Small molecule potentiators, previously identified in CFTR binding studies, were tested for activity in augmenting CFTR channel activity using patch clamp electrophysiology in HEK-293 cells, a fluorescence-based assay of membrane potential in Calu-3 cells and in Ussing chamber studies of primary bronchial epithelial cultures. Addition of cigarette smoke extract (CSE) to the solutions bathing the apical surface of Calu-3 cells and primary bronchial airway cultures was used to model COPD. Confocal studies of the velocity of fluorescent microsphere movement on the apical surface of CSE exposed airway epithelial cultures, were used to assess the effect of potentiators on CFTR-mediated mucociliary movement. Results We showed that SK-POT1, like VX-770, was effective in augmenting the cyclic AMP-dependent channel activity of CFTR. SK-POT-1 enhanced CFTR channel activity in airway epithelial cells previously exposed to CSE and ameliorated mucostasis on the surface of primary airway cultures. Conclusion Together, this evidence supports the further development of SK-POT1 as an intervention in the treatment of COPD.

Abstract The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune receptor that affects cellular phenotypes by modulating phagocytosis and metabolism, promoting cell survival, and counteracting inflammation. Its role in renal injury, in particular, unilateral ureteral obstruction (UUO) or ischemia-reperfusion injury (IRI)-induced renal injury remains unclear. In our study, WT and Trem2 −/− mice were employed to evaluate the role of TREM2 in renal macrophage infiltration and tissue injury after UUO. Bone marrow-derived macrophages (BMDM) from both mouse genotypes were cultured and polarized for in vitro experiments. Next, the effects of TREM2 on renal injury and macrophage polarization in IRI mice were also explored. We found that TREM2 expression was upregulated in the obstructed kidneys. TREM2 deficiency exacerbated renal inflammation and fibrosis 3 and 7 days after UUO, in association with reduced macrophage infiltration. Trem2 −/− BMDM exhibited increased apoptosis and poorer survival compared with WT BMDM. Meanwhile, TREM2 deficiency augmented M1 and M2 polarization after UUO. Consistent with the in vivo observations, TREM2 deficiency led to increased polarization of BMDM towards the M1 proinflammatory phenotype. Mechanistically, TREM2 deficiency promoted M1 and M2 polarization via the JAK-STAT pathway in the presence of TGF-β1, thereby affecting cell survival by regulating mTOR signaling. Furthermore, cyclocreatine supplementation alleviated cell death caused by TREM2 deficiency. Additionally, we found that TREM2 deficiency promoted renal injury, fibrosis, and macrophage polarization in IRI mice. The current data suggest that TREM2 deficiency aggravates renal injury by promoting macrophage apoptosis and polarization via the JAK-STAT pathway. These findings have implications for the role of TREM2 in the regulation of renal injury that justify further evaluation.

Soil metabolomics is an emerging approach for profiling diverse small molecule metabolites, i.e., metabolomes, in the soil. Soil metabolites, including fatty acids, amino acids, lipids, organic acids, sugars, and volatile organic compounds, often contain essential nutrients such as nitrogen, phosphorus, and sulfur and are directly linked to soil biogeochemical cycles driven by soil microorganisms. This paper presents an overview of methods for analyzing soil metabolites and the state-of-the-art of soil metabolomics in relation to soil nutrient cycling. We describe important applications of metabolomics in studying soil carbon cycling and sequestration, and the response of soil organic pools to changing environmental conditions. This includes using metabolomics to provide new insights into the close relationships between soil microbiome and metabolome, as well as responses of soil metabolome to plant and environmental stresses such as soil contamination. We also highlight the advantage of using soil metabolomics to study the biogeochemical cycles of elements and suggest that future research needs to better understand factors driving soil function and health.