A novel and low-cost cross-priming amplification assay for rapid detection of Babesia duncani infection.

Babesia duncani, responsible for human babesiosis, is one of the most important tick-borne intraerythrocytic pathogens. Traditionally, babesiosis is definitively diagnosed by detecting parasite DNA in blood samples and examining Babesia parasites in Giemsa-stained peripheral blood smears. Although these techniques are valuable for determining Babesia duncani, they are often time-consuming and laborious. Therefore, developing rapid and reliable B. duncani identification assays is essential for subsequent epidemiological investigations and prevention and control. In this study, a cross-priming amplification (CPA) assay was developed, combined with a vertical flow visualization strip, to rapidly and accurately detect B. duncani infection. The detection limit of this method was as low as 0.98 pg/µl of genomic DNA from B. duncani merozoites per reaction at 59 °C for 60 min. There were no cross-reactions between B. duncani and other piroplasms infective to humans and mammals. A total of 592 blood samples from patients bitten by ticks and experimental infected hamsters were accurately assessed using CPA assay. The average cost of the CPA assay is as low as approximately $ 0.2 per person. These findings indicate that the CPA assay may therefore be a rapid screening tool for detection B. duncani infection, based on its accuracy, speed, and cost-effectiveness, particularly in resource-limited regions with a high prevalence of human babesiosis.

Clinical predictive value of pre-pregnancy tests for unexplained recurrent spontaneous abortion: a retrospective study.

Introduction: Early prediction and intervention are crucial for the prognosis of unexplained recurrent spontaneous abortion (uRSA). The main purpose of this study is to establish a risk prediction model for uRSA based on routine pre-pregnancy tests, in order to provide clinical physicians with indications of whether the patients are at high risk. Methods: This was a retrospective study conducted at the Prenatal Diagnosis Center of Henan Provincial People's Hospital between January 2019 and December 2022. Twelve routine pre-pregnancy tests and four basic personal information characteristics were collected. Pre-pregnancy tests include thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine thyroid (FT4), thyroxine (TT4), total triiodothyronine (TT3), peroxidase antibody (TPO-Ab), thyroid globulin antibody (TG-Ab), 25-hydroxyvitamin D [25-(OH) D], ferritin (Ferr), Homocysteine (Hcy), vitamin B12 (VitB12), folic acid (FA). Basic personal information characteristics include age, body mass index (BMI), smoking history and drinking history. Logistic regression analysis was used to establish a risk prediction model, and receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were employed to evaluate the performance of prediction model. Results: A total of 140 patients in uRSA group and 152 women in the control group were randomly split into a training set (n = 186) and a testing set (n = 106). Chi-square test results for each single characteristic indicated that, FT3 (p = 0.018), FT4 (p = 0.048), 25-(OH) D (p = 0.013) and FA (p = 0.044) were closely related to RSA. TG-Ab and TPO-Ab were also important characteristics according to clinical experience, so we established a risk prediction model for RSA based on the above six characteristics using logistic regression analysis. The prediction accuracy of the model on the testing set was 74.53%, and the area under ROC curve was 0.710. DCA curve indicated that the model had good clinical value. Conclusion: Pre-pregnancy tests such as FT3, FT4, TG-Ab, 25-(OH)D and FA were closely related to uRSA. This study successfully established a risk prediction model for RSA based on routine pre-pregnancy tests.

Selenomethionine supplementation mitigates fluoride-induced liver apoptosis and inflammatory reactions by blocking Parkin-mediated mitophagy in mice.

As an environmental pollutant, fluoride-induced liver damage is directly linked to mitochondrial alteration and oxidative stress. Selenium's antioxidant capacity has been shown to alleviate liver damage. Emerging research proves that E3 ubiquitin ligase Park2 (Parkin)-mediated mitophagy may be a therapeutic target for fluorosis. The current study explored the effect of diverse selenium sources on fluoride-caused liver injury and the role of Parkin-mediated mitophagy in this intervention process. Therefore, this study established a fluoride-different selenium sources co-intervention wild-type (WT) mouse model and a fluoride-optimum selenium sources co-intervention Parkin gene knockout (Parkin-/-) mouse model. Our results show that selenomethionine (SeMet) is the optimum selenium supplementation form for mice suffering from fluorosis when compared to sodium selenite and chitosan nano­selenium because mice from the F-SeMet group showed more closely normal growth and development levels of liver function, antioxidant capacity, and anti-inflammatory ability. Explicitly, SeMet ameliorated liver inflammation and cell apoptosis in fluoride-toxic mice, accomplished through downregulating the mRNA and protein expression levels associated with mitochondrial fusion and fission, mitophagy, apoptosis, inflammatory signalling pathway of nuclear factor-kappa B (NF-κB), reducing the protein expression levels of PARKIN, PTEN-induced putative kinase1 (PINK1), SQSTM1/p62 (P62), microtubule-associated protein light chain 3 (LC3), cysteinyl aspartate specific proteinase 3 (CASPAS3), as well as restraining the content of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and interferon-γ (IFN-γ). The Parkin-/- showed comparable positive effects to the SeMet in the liver of fluorosis mice. The structure of the mitochondria, mRNA, protein expression levels, and the content of proinflammatory factors in mice from the FParkin-/- and F + SeMetParkin-/- groups closely resembled those in the F + SeMetWT group. Overall, the above results indicated that SeMet could alleviate fluoride-triggered inflammation and apoptosis in mice liver via blocking Parkin-mediated mitophagy.

A novel CAF-cancer cell crosstalk-related gene prognostic index based on machine learning: prognostic significance and prediction of therapeutic response in head and neck squamous cell carcinoma.

BACKGROUND: Cancer-associated fibroblast (CAF)-cancer cell crosstalk (CCCT) plays an important role in tumor microenvironment shaping and immunotherapy response. Current prognostic indexes are insufficient to accurately assess immunotherapy response in patients with head and neck squamous cell carcinoma (HNSCC). This study aimed to develop a CCCT-related gene prognostic index (CCRGPI) for assessing the prognosis and response to immune checkpoint inhibitor (ICI) therapy of HNSCC patients. METHODS: Two cellular models, the fibroblast-cancer cell indirect coculture (FCICC) model, and the fibroblast-cancer cell organoid (FC-organoid) model, were constructed to visualize the crosstalk between fibroblasts and cancer cells. Based on a HNSCC scRNA-seq dataset, the R package CellChat was used to perform cell communication analysis to identify gene pairs involved in CCCT. Least absolute shrinkage and selection operator (LASSO) regression was then applied to further refine the selection of these gene pairs. The selected gene pairs were subsequently subjected to stepwise regression to develop CCRGPI. We further performed a comprehensive analysis to determine the molecular and immune characteristics, and prognosis associated with ICI therapy in different CCRGPI subgroups. Finally, the connectivity map (CMap) analysis and molecular docking were used to screen potential therapeutic drugs. RESULTS: FCICC and FC-organoid models showed that cancer cells promoted the activation of fibroblasts into CAFs, that CAFs enhanced the invasion of cancer cells, and that CCCT was somewhat heterogeneous. The CCRGPI was developed based on 4 gene pairs: IGF1-IGF1R, LGALS9-CD44, SEMA5A-PLXNA1, and TNXB-SDC1. Furthermore, a high CCRGPI score was identified as an adverse prognostic factor for overall survival (OS). Additionally, a high CCRGPI was positively correlated with the activation of the P53 pathway, a high TP53 mutation rate, and decreased benefit from ICI therapy but was inversely associated with the abundance of various immune cells, such as CD4+ T cells, CD8+ T cells, and B cells. Moreover, Ganetespib was identified as a potential drug for HNSCC combination therapy. CONCLUSIONS: The CCRGPI is reliable for predicting the prognosis and immunotherapy response of HSNCC patients and may be useful for guiding the individualized treatment of HNSCC patients.

Deep reinforcement learning task scheduling method based on server real-time performance.

Server load levels affect the performance of cloud task execution, which is rooted in the impact of server performance on cloud task execution. Traditional cloud task scheduling methods usually only consider server load without fully considering the server's real-time load-performance mapping relationship, resulting in the inability to evaluate the server's real-time processing capability accurately. This deficiency directly affects the efficiency, performance, and user experience of cloud task scheduling. Firstly, we construct a performance platform model to monitor server real-time load and performance status information in response to the above problems. In addition, we propose a new deep reinforcement learning task scheduling method based on server real-time performance (SRP-DRL). This method introduces a real-time performance-aware strategy and adds status information about the real-time impact of task load on server performance on top of considering server load. It enhances the perception capability of the deep reinforcement learning (DRL) model in cloud scheduling environments and improves the server's load-balancing ability under latency constraints. Experimental results indicate that the SRP-DRL method has better overall performance regarding task average response time, success rate, and server average load variance compared to Random, Round-Robin, Earliest Idle Time First (EITF), and Best Fit (BEST-FIT) task scheduling methods. In particular, the SRP-DRL is highly effective in reducing server average load variance when numerous tasks arrive within a unit of time, ultimately optimizing the performance of the cloud system.

Parametric analysis of craniocerebral injury mechanism in pedestrian traffic accidents based on finite element methods.

PURPOSE: The toughest challenge in pedestrian traffic accident identification lies in ascertaining injury manners. This study aimed to systematically simulate and parameterize 3 types of craniocerebral injury including impact injury, fall injury, and run-over injury, to compare the injury response outcomes of different injury manners. METHODS: Based on the total human model for safety (THUMS) and its enhanced human model THUMS-hollow structures, a total of 84 simulations with 3 injury manners, different loading directions, and loading velocities were conducted. Von Mises stress, intracranial pressure, maximum principal strain, cumulative strain damage measure, shear stress, and cranial strain were employed to analyze the injury response of all areas of the brain. To examine the association between injury conditions and injury consequences, correlation analysis, principal component analysis, linear regression, and stepwise linear regression were utilized. RESULTS: There is a significant correlation observed between each criterion of skull and brain injury (p < 0.01 in all Pearson correlation analysis results). A 2-phase increase of cranio-cerebral stress and strain as impact speed increases. In high-speed impact (> 40 km/h), the Von Mises stress on the skull was with a high possibility exceed the threshold for skull fracture (100 MPa). When falling and making temporal and occipital contact with the ground, the opposite side of the impacted area experiences higher frequency stress concentration than contact at other conditions. Run-over injuries tend to have a more comprehensive craniocerebral injury, with greater overall deformation due to more adequate kinetic energy conduction. The mean value of maximum principal strain of brain and Von Mises stress of cranium at run-over condition are 1.39 and 403.8 MPa, while they were 1.31, 94.11 MPa and 0.64, 120.5 MPa for the impact and fall conditions, respectively. The impact velocity also plays a significant role in craniocerebral injury in impact and fall loading conditions (the p of all F-test < 0.05). A regression equation of the craniocerebral injury manners in pedestrian accidents was established. CONCLUSION: The study distinguished the craniocerebral injuries caused in different manners, elucidated the biomechanical mechanisms of craniocerebral injury, and provided a biomechanical foundation for the identification of craniocerebral injury in legal contexts.

Zeb1-controlled metabolic plasticity enables remodeling of chromatin accessibility in the development of neuroendocrine prostate cancer.

Cell plasticity has been found to play a critical role in tumor progression and therapy resistance. However, our understanding of the characteristics and markers of plastic cellular states during cancer cell lineage transition remains limited. In this study, multi-omics analyses show that prostate cancer cells undergo an intermediate state marked by Zeb1 expression with epithelial-mesenchymal transition (EMT), stemness, and neuroendocrine features during the development of neuroendocrine prostate cancer (NEPC). Organoid-formation assays and in vivo lineage tracing experiments demonstrate that Zeb1+ epithelioid cells are putative cells of origin for NEPC. Mechanistically, Zeb1 transcriptionally regulates the expression of several key glycolytic enzymes, thereby predisposing tumor cells to utilize glycolysis for energy metabolism. During this process, lactate accumulation-mediated histone lactylation enhances chromatin accessibility and cellular plasticity including induction of neuro-gene expression, which promotes NEPC development. Collectively, Zeb1-driven metabolic rewiring enables the epigenetic reprogramming of prostate cancer cells to license the adeno-to-neuroendocrine lineage transition.

Hydrogen-Bonded Organic Framework Supporting Atomic Bi-N2O2 Sites for High-Efficiency Electrocatalytic CO2 Reduction.

Single atomic catalysts (SACs) offer a superior platform for studying the structure-activity relationships during electrocatalytic CO2 reduction reaction (CO2RR). Yet challenges still exist to obtain well-defined and novel site configuration owing to the uncertainty of functional framework-derived SACs through calcination. Herein, a novel Bi-N2O2 site supported on the (1 1 0) plane of hydrogen-bonded organic framework (HOF) is reported directly for CO2RR. In flow cell, the target catalyst Bi1-HOF maintains a faradaic efficiency (FE) HCOOH of over 90 % at a wide potential window of 1.4 V. The corresponding partial current density ranges from 113.3 to 747.0 mA cm-2. And, Bi1-HOF exhibits a long-term stability of over 30 h under a successive potential-step test with a current density of 100-400 mA cm-2. Density function theory (DFT) calculations illustrate that the novel Bi-N2O2 site supported on the (1 1 0) plane of HOF effectively induces the oriented electron transfer from Bi center to CO2 molecule, reaching an enhanced CO2 activation and reduction. Besides, this study offers a versatile method to reach series of M-N2O2 sites with regulable metal centers via the same intercalation mechanism, broadening the platform for studying the structure-activity relationships during CO2RR.

A review of "plant gold" Eucommia ulmoides Oliv.: A medicinal and food homologous plant with economic value and prospect.

Eucommia ulmoides Oliv. is an ancient and precious plant that has been used as medicine in China for more than 2000 years. Because its bark, leaves, seeds, and male flowers can be used in medicine, it plays an important role in medicine, food, chemical industry, and other fields, so it is also called "plant gold". 246 compounds have been isolated from E. ulmoides, which endow E. ulmoides with many unique pharmacological effects and make it wide to study in the fields of osteoporosis, hypertension, liver protection, and so on. Besides, E. ulmoides also has significant medicinal effects on anti-inflammatory, antioxidant, immunomodulation, and neuroprotection, and is often used in clinical compound medicines of traditional Chinese medicine. In addition to updating its ethnobotany, phytochemistry, pharmacology, and toxicology information, the economic botany of leaves, seeds, and male flowers was also introduced. It hopes hoping to fully understand this economically important Chinese medicine and provide a scientific basis for further development and utilization of E. ulmoides.

Regulating d-Orbital Hybridization of Subgroup-IVB Single Atoms for Efficient Oxygen Reduction Reaction.

Highly active single-atom electrocatalysts for the oxygen reduction reaction are crucial for improving the energy conversion efficiency, but they suffer from a limited choice of metal centers and unsatisfactory stabilities. Here, this work reports that optimization of the binding energies for reaction intermediates by tuning the d-orbital hybridization with axial groups converts inactive subgroup-IVB (Ti, Zr, Hf) moieties (MN4) into active motifs (MN4O), as confirmed with theoretical calculations. The competition between metal-ligand covalency and metal-intermediate covalency affects the d-p orbital hybridization between the metal site and the intermediates, converting the metal centers into active sites. Subsequently, dispersed single-atom M sites coordinated by nitrogen/oxygen groups have been prepared on graphene (s-M-N/O-C) catalysts on a large-scale with high-energy milling and pyrolysis. Impressively, the s-Hf-N/O-C catalyst with 5.08 wt% Hf exhibits a half-wave potential of 0.920 V and encouraging performance in a zinc-air battery with an extraordinary cycling life of over 1600 h and a large peak power-density of 256.9 mW cm-2. This work provides promising single-atom electrocatalysts and principles for preparing other catalysts for the oxygen reduction reaction.

Probiotic Bacillus licheniformis ZW3 Alleviates DSS-Induced Colitis and Enhances Gut Homeostasis.

Despite Bacillus species having been extensively utilized in the food industry and biocontrol as part of probiotic preparations, limited knowledge exists regarding their impact on intestinal disorders. In this study, we investigated the effect of Bacillus licheniformis ZW3 (ZW3), a potential probiotic isolated from camel feces, on dextran sulfate sodium (DSS)-induced colitis. The results showed ZW3 partially mitigated body weight loss, disease activity index (DAI), colon shortening, and suppressed immune response in colitis mice, as evidenced by the reduction in the levels of the inflammatory markers IL-1ß, TNF-α, and IL-6 (p < 0.05). ZW3 was found to ameliorate DSS-induced dysfunction of the colonic barrier by enhancing mucin 2 (MUC2), zonula occluden-1 (ZO-1), and occludin. Furthermore, enriched beneficial bacteria Lachnospiraceae_NK4A136_group and decreased harmful bacteria Escherichia-Shigella revealed that ZW3 improved the imbalanced gut microbiota. Abnormally elevated uric acid levels in colitis were further normalized upon ZW3 supplementation. Overall, this study emphasized the protective effects of ZW3 in colitis mice as well as some potential applications in the management of inflammation-related diseases.

Calcium supplementation attenuates fluoride-induced bone injury via PINK1/Parkin-mediated mitophagy and mitochondrial apoptosis in mice.

Excessive consumption of fluoride can cause skeletal fluorosis. Mitophagy has been identified as a novel target for bone disorders. Meanwhile, calcium supplementation has shown great potential for mitigating fluoride-related bone damage. Hence, this study aimed to elucidate the association between mitophagy and skeletal fluorosis and the precise mechanisms through which calcium alleviates these injuries. A 100 mg/L sodium fluoride (NaF) exposure model in Parkin knockout (Parkin-/-) mice and a 100 mg/L NaF exposure mouse model with 1% calcium carbonate (CaCO3) intervention were established in the current study. Fluoride exposure caused the impairment of mitochondria and activation of PTEN-induced putative kinase1 (PINK1)/E3 ubiquitin ligase Park2 (Parkin)-mediated mitophagy and mitochondrial apoptosis in the bones, which were restored after blocking Parkin. Additionally, the intervention model showed fluoride-exposed mice exhibited abnormal bone trabecula and mechanical properties. Still, these bone injuries could be effectively attenuated by adding 1% calcium to their diet, which reversed fluoride-activated mitophagy and apoptosis. To summarize, fluoride can activate bone mitophagy through the PINK1/Parkin pathway and mitochondrial apoptosis. Parkin-/- and 1% calcium provide protection against fluoride-induced bone damage. Notably, this study provides theoretical bases for the prevention and therapy of animal and human health and safety caused by environmental fluoride contamination.

Insight into Hyalomma anatolicum biology by comparative genomics analyses.

Hyalomma anatolicum is an obligatory blood-sucking ectoparasite and contributes to the transmission of Crimean-Congo haemorrhagic fever (CCHF) virus, Theileria spp. and Babesia spp. Progress in exploring the adaptive strategy of this ectoparasite and developing tools to fight it has been hindered by the lack of a complete genome. Herein, we assembled the genome using diverse sources of data from multiple sequencing platforms and annotated the 1.96 Gb genome of Hy. anatolicum. Comparative genome analyses and the predicted protein encoding genes reveal unique facets of this genome, including gene family expansion associated with blood feeding and digestion, multi-gene families involved in detoxification, a great number of neuropeptides and corresponding receptors regulating tick growth, development, and reproduction, and glutathione S-transferase genes playing roles in insecticide resistance and detoxification of multiple xenobiotic factors. This high quality reference genome provides fundamental data for obtaining insights into a variety of aspects of tick biology and developing novel strategies to fight notorious tick vectors of human and animal pathogens.

The Microbial Tryptophan Metabolite Contributes to the Remission of Salmonella typhimurium Infection in Mice.

Salmonella enterica serovar Typhimurium (S. Tm) causes severe foodborne diseases. Interestingly, gut microbial tryptophan (Trp) metabolism plays a pivotal role in such infections by a yet unknown mechanism. This study aimed to explore the impact of Trp metabolism on S. Tm infection and the possible mechanisms involved. S. Tm-infected C57BL6/J mice were used to demonstrate the therapeutic benefits of the Bacillus velezensis JT3-1 (B. velezensis/JT3-1) strain or its cell-free supernatant in enhancing Trp metabolism. Targeted Trp metabolomic analyses indicated the predominance of indole-3-lactic acid (ILA), an indole derivative and ligand for aryl hydrocarbon receptor (AHR). Based on the 16S amplicon sequencing and correlation analysis of metabolites, we found that B. velezensis supported the relative abundance of Lactobacillus and Ligilactobacillus in mouse gut and showed positive correlations with ILA levels. Moreover, AHR and its downstream genes (especially IL-22) significantly increased in mouse colons after B. velezensis or cell-free supernatant treatment, suggesting the importance of AHR pathway activation. In addition, ILA was found to stimulate primary mouse macrophages to secrete IL-22, which was antagonized by CH-223191. Furthermore, ILA could protect mice from S. Tm infection by increasing IL-22 in Ahr+/- mice, but not in Ahr-/- mice. Finally, Trp-rich feeding showed amelioration of S. Tm infection in mice, and the effect depended on gut microbiota. Taken together, these results suggest that B. velezensis-associated ILA contributes to protecting mice against S. Tm infection by activating the AHR/IL-22 pathway. This study provides insights into the involvement of microbiota-derived Trp catabolites in protecting against Salmonella infection.

A Sodiophilic Amyloid Fibril Modified Separator for Dendrite-Free Sodium-Metal Batteries.

Sodium (Na) batteries are being considered as prospective candidates for the next generation of secondary batteries in contrast to lithium-based batteries, due to their high raw-material abundance, low cost, and sustainability. However, the unfavorable growth of Na-metal deposition and severe interfacial reactions have prevented their large-scale applications. Here, a vacuum filtration strategy, through amyloid-fibril-modified glass-fiber separators, is proposed to address these issues. The modified symmetric cell can be cycled for 1800 h, surpassing the performance of previously reported Na-based electrodes under an ester-based electrolyte. Moreover, the Na/Na3 V2 (PO4 )3 full cell with a sodiophilic amyloid-fibril-modified separator exhibits a capacity retention of 87.13% even after 1000 cycles. Both the experimental and the theoretical results show that the sodiophilic amyloid fibril homogenizes the electric field and Na-ion concentration, fundamentally inhibiting dendrite formation. Simultaneously, the glutamine amino acids in the amyloid fibril have the highest adsorption energy for Na, resulting in the formation of a stable Na3 N- and NaNx Oy -rich solid-electrolyte-interface film on the anode during cycling. This work provides not only a possible pathway to solve the dendrite problem in metal batteries using environmentally friendly biomacromolecular materials, but also a new direction for expanding biomaterial applications.

Accuracy of digital guided implant surgery: expert consensus on nonsurgical factors and their treatments / 口腔疾病防治

@#The standardized workflow of computer-aided static guided implant surgery includes preoperative examination, data acquisition, guide design, guide fabrication and surgery. Errors may occur at each step, leading to irreversible cumulative effects and thus impacting the accuracy of implant placement. However, clinicians tend to focus on factors causing errors in surgical operations, ignoring the possibility of irreversible errors in nonstandard guided surgery. Based on the clinical practice of domestic experts and research progress at home and abroad, this paper summarizes the sources of errors in guided implant surgery from the perspectives of preoperative inspection, data collection, guide designing and manufacturing and describes strategies to resolve errors so as to gain expert consensus. Consensus recommendation: 1. Preoperative considerations: the appropriate implant guide type should be selected according to the patient's oral condition before surgery, and a retaining screw-assisted support guide should be selected if necessary. 2. Data acquisition should be standardized as much as possible, including beam CT and extraoral scanning. CBCT performed with the patient’s head fixed and with a small field of view is recommended. For patients with metal prostheses inside the mouth, a registration marker guide should be used, and the ambient temperature and light of the external oral scanner should be reasonably controlled. 3. Optimization of computer-aided design: it is recommended to select a handle-guided planting system and a closed metal sleeve and to register images by overlapping markers. Properly designing the retaining screws, extending the support structure of the guide plate and increasing the length of the guide section are methods to feasibly reduce the incidence of surgical errors. 4. Improving computer-aided production: it is also crucial to set the best printing parameters according to different printing technologies and to choose the most appropriate postprocessing procedures.

ADORA2A-driven proline synthesis triggers epigenetic reprogramming in neuroendocrine prostate and lung cancers.

Cell lineage plasticity is one of the major causes for the failure of targeted therapies in various cancers. However, the driver and actionable drug targets in promoting cancer cell lineage plasticity are scarcely identified. Here, we found that a G protein-coupled receptor, ADORA2A, is specifically upregulated during neuroendocrine differentiation, a common form of lineage plasticity in prostate cancer and lung cancer following targeted therapies. Activation of the ADORA2A signaling rewires the proline metabolism via an ERK/MYC/PYCR cascade. Increased proline synthesis promotes deacetylases SIRT6/7-mediated deacetylation of histone H3 at lysine 27 (H3K27), and thereby biases a global transcriptional output toward a neuroendocrine lineage profile. Ablation of Adora2a in genetically engineered mouse models inhibits the development and progression of neuroendocrine prostate and lung cancers, and, intriguingly, prevents the adenocarcinoma-to-neuroendocrine phenotypic transition. Importantly, pharmacological blockade of ADORA2A profoundly represses neuroendocrine prostate and lung cancer growth in vivo. Therefore, we believe that ADORA2A can be used as a promising therapeutic target to govern the epigenetic reprogramming in neuroendocrine malignancies.

Importance of optimizing duration of adjuvant immune checkpoint inhibitor therapy to treat postoperative hepatocellular carcinoma after conversion therapy: a case report.

Patients with hepatocellular carcinoma at high risk of recurrence after hepatic resection or local ablation often undergo adjuvant immunotherapy with immune checkpoint inhibitors for 1 year in randomized controlled trials, but the appropriateness of this duration is controversial, especially given the risk of adverse events. Here we report the case of a 52-year-old Chinese man with initially unresectable multinodular recurrent hepatocellular carcinoma who underwent two cycles of transarterial chemoembolization, followed by hepatic resection and 24 months of adjuvant therapy with the PD-1 inhibitor tislelizumab. The patient achieved a recurrence-free survival time of 24 months, but he experienced elevated alpha fetoprotein, Grade 2 hypothyroidism and pruritus while on adjuvant therapy. This case highlights the need to optimize the duration of adjuvant immunotherapy after curative treatment for hepatocellular carcinoma in order to minimize risk of not only recurrence but also adverse events.

OpiCa1-PEG-PLGA nanomicelles antagonize acute heart failure induced by the cocktail of epinephrine and caffeine.

Background: Reducing Ca2+ content in the sarcoplasmic reticulum (SR) through ryanodine receptors (RyRs) by calcin is a potential intervention strategy for the SR Ca2+ overload triggered by ß-adrenergic stress in acute heart diseases. Methods: OpiCal-PEG-PLGA nanomicelles were prepared by thin film dispersion, of which the antagonistic effects were observed using an acute heart failure model induced by epinephrine and caffeine in mice. In addition, cardiac targeting, self-stability as well as biotoxicity were determined. Results: The synthesized OpiCa1-PEG-PLGA nanomicelles were elliptical with a particle size of 72.26 nm, a PDI value of 0.3, and a molecular weight of 10.39 kDa. The nanomicelles showed a significant antagonistic effect with 100 % survival rate to the death induced by epinephrine and caffeine, which was supported by echocardiography with significantly recovered heart rate, ejection fraction and left ventricular fractional shortening rate. The FITC labeled nanomicelles had a strong membrance penetrating capacity within 2 h and cardiac targeting within 12 h that was further confirmed by immunohistochemistry with a self-prepared OpiCa1 polyclonal antibody. Meanwhile, the nanomicelles can keep better stability and dispersibility in vitro at 4 °C rather than 20 °C or 37 °C, while maintain a low but stable plasma OpiCa1 concentration in vivo within 72 h. Finally, no obvious biotoxicities were observed by CCK-8, flow cytometry, H&E staining and blood biochemical examinations. Conclusion: Our study also provide a novel nanodelivery pathway for targeting RyRs and antagonizing the SR Ca2+ disordered heart diseases by actively releasing SR Ca2+ through RyRs with calcin.

Assessment of soil quality in an arid and barren mountainous of Shandong province, China.

Forest soils are important components of forest ecosystems, and soil quality assessment as a decision-making tool to understand forest soil quality and maintain soil productivity is essential. Various methods of soil quality assessment have been developed, which have occasionally generated inconsistent assessment results between soil types. We assessed the soil quality of five communities (herb, shrub, Quercus acutissima, Pinus thunbergii, and Q. acutissima-P. thunbergii mixed plantation) using two common methods of dry and barren mountains in the Yimeng Mountain area, China. Sixteen soil physical, chemical and biological properties were analysed. The soil quality index was determined using the established minimum data set based on the selection results of principal component analysis and Pearson analysis. Silt, soil total phosphorus (P), soil total nitrogen (N), L-leucine aminopeptidase, acid phosphatase and vector length were identified as the most representative indicators for the minimum data set. Linear regression analysis showed that the minimum data set can adequately represent the total data set to quantify the impact of different communities on soil quality (P < 0.001). The results of linear and non-linear methods of soil quality assessment showed that the higher soil quality index was Pinus forest (0.59 and 0.54), and the soil quality index of mixed plantation (0.41 and 0.45) was lower, which was similar to the herb community (0.37 and 0.44). Soil quality was mostly affected by soil chemical properties and extracellular enzyme activities of different communities, and the different reasons for the low soil quality of mixed plantations were affected by soil organic carbon (C) and total C. Overall, we demonstrate that the soil quality index based on the minimum data set method could be a useful tool to indicate the soil quality of forest systems. Mixed plantations can improve soil quality by increasing soil C, which is crucial in ecosystem balance.