Integrated transcriptomics and proteomics analyses reveal the ameliorative effect of hepatic damage in tilapia caused by polystyrene microplastics with chlorella addition.

Fish exhibit varying responses to polystyrene microplastics (MPs) depending on particle size. Previous studies suggested that microorganisms adhering to the surface of MPs can induce toxic effects. In this study, Tilapia were exposed to MPs of control (group A), 75 nm (B), 7.5 µm (C), 750 µm (D), as well as combinations of all sizes (E) and 75 nm MPs with Chlorella vulgaris addition (F) for 7, 10 and 14 days. Histopathological changes in liver of tilapia were assessed using enzyme activities, transcriptomics and proteomics. The results showed that in groups combined MPs of different particle sizes and those supplemented with chlorella, MPs were localized on the surface of goblet cells, leading to vacuoles, constricted hepatic sinuses and nuclei displacement. Exposure to 7.5 and 750 µm MPs significantly increased the contents of fatty acid synthase (FAS), adenosine triphosphate (ATP), acetyl-CoA carboxylase (ACC), lipoprotein lipase (LPL), total cholesterol (TC), total triglyceride (TG) contents at 7 and 10 days. In particular, cytochrome p450 1a1 (EROD), reactive oxygen species (ROS) and superoxide dismutase (SOD) were markedly elevated following exposure to MPs. Apoptotic markers caspase-3, and inflammatory markers, including tumor necrosis factor α (TNF-α) and interleukin-1ß (IL-1ß), had a similar upward trend in comparisons of group C vs A at 7 d, group D vs A at 14 d. The peroxisome proliferator activated receptor (PPAR) signaling pathway, spliceosome, was highly enriched during the 7-day exposure of medium sized MPs, while largest MPs in the comparison of group D vs A at 14 d activated pathways such as phagosome, apoptosis, salmonella infection. Transcriptomic analysis revealed that after 14 days, the kyoto encyclopedia of genes and genomes (KEGG) pathways associated with protein processing in endoplasmic reticulum and the PPAR signaling has been significantly enriched in the Chlorella-supplemented group, which was further confirmed via the proteomic analysis. Overall, the findings highlight the size-dependent effects of MPs on histopathological changes, gene and protein expression in the liver of tilapia, and C. vulgaris effectively attenuated liver damages, likely through modulation of endoplasmic reticulum protein processing and PPAR signaling pathways.

Nickel-Catalyzed Cyanation of Allylic Alcohols: High Degree of Chiral Inversion in Aqueous Reaction Media.

Nickel-catalyzed aqueous cyanation of allylic alcohols is herein described. This catalytic protocol provided environmentally friendly and operationally simple access to a variety of allylic nitriles in good yields. For chiral allylic alcohols, the reaction gave chiral allylic nitriles with a high degree of chiral inversion. The accelerated release of cyanide in H2O was crucial for the success of this reaction.

Salt-Assisted, In Situ Current Nanowelding of an Interfacial Au Nanoparticle Film for a High-Performance Electrocatalyst.

Interfacial self-assembly is a well-established method for the preparation of a two-dimensional (2D) metal nanofilm from nanoscale building blocks. However, the as-prepared nanofilm exhibits limited conductivity because of the large contact resistance at the junctions among its building blocks. Here, we report a salt-assisted, in situ current nanowelding strategy to weld an interfacial Au nanoparticle (NP) film for downstream applications, such as high-performance electrocatalysts. Particularly, we found that salt-assisted interfacial assembly can reduce the size of the nanogaps among neighboring Au NPs and, in turn, greatly improve the conductivity of the resultant Au NP film. Consequently, the Au NP film can be readily welded using current, and the welding extent can be monitored in real-time by looking at the passing current. The welding finally produces a nanoporous Au film (NPGF) with a network nanostructure, high conductivity, and abundant active sites so that it delivers a large current density of 86.96 µA·cm-2 (1.81 times higher than that from the pristine Au NP film) and shows improved cycling stability for methanol electrooxidation. Thus, these results offer a low-cost, solution-processable approach for the fabrication of a large-area, interconnected nanofilm from nanoscale building blocks beyond Au NPs, which may find diverse downstream applications.

Assessing and Optimizing Large Language Models on Spondyloarthritis Multi-Choice Question Answering: Protocol for Enhancement and Assessment.

BACKGROUND: Spondyloarthritis (SpA), a chronic inflammatory disorder, predominantly impacts the sacroiliac joints and spine, significantly escalating the risk of disability. SpA's complexity, as evidenced by its diverse clinical presentations and symptoms that often mimic other diseases, presents substantial challenges in its accurate diagnosis and differentiation. This complexity becomes even more pronounced in nonspecialist health care environments due to limited resources, resulting in delayed referrals, increased misdiagnosis rates, and exacerbated disability outcomes for patients with SpA. The emergence of large language models (LLMs) in medical diagnostics introduces a revolutionary potential to overcome these diagnostic hurdles. Despite recent advancements in artificial intelligence and LLMs demonstrating effectiveness in diagnosing and treating various diseases, their application in SpA remains underdeveloped. Currently, there is a notable absence of SpA-specific LLMs and an established benchmark for assessing the performance of such models in this particular field. OBJECTIVE: Our objective is to develop a foundational medical model, creating a comprehensive evaluation benchmark tailored to the essential medical knowledge of SpA and its unique diagnostic and treatment protocols. The model, post-pretraining, will be subject to further enhancement through supervised fine-tuning. It is projected to significantly aid physicians in SpA diagnosis and treatment, especially in settings with limited access to specialized care. Furthermore, this initiative is poised to promote early and accurate SpA detection at the primary care level, thereby diminishing the risks associated with delayed or incorrect diagnoses. METHODS: A rigorous benchmark, comprising 222 meticulously formulated multiple-choice questions on SpA, will be established and developed. These questions will be extensively revised to ensure their suitability for accurately evaluating LLMs' performance in real-world diagnostic and therapeutic scenarios. Our methodology involves selecting and refining top foundational models using public data sets. The best-performing model in our benchmark will undergo further training. Subsequently, more than 80,000 real-world inpatient and outpatient cases from hospitals will enhance LLM training, incorporating techniques such as supervised fine-tuning and low-rank adaptation. We will rigorously assess the models' generated responses for accuracy and evaluate their reasoning processes using the metrics of fluency, relevance, completeness, and medical proficiency. RESULTS: Development of the model is progressing, with significant enhancements anticipated by early 2024. The benchmark, along with the results of evaluations, is expected to be released in the second quarter of 2024. CONCLUSIONS: Our trained model aims to capitalize on the capabilities of LLMs in analyzing complex clinical data, thereby enabling precise detection, diagnosis, and treatment of SpA. This innovation is anticipated to play a vital role in diminishing the disabilities arising from delayed or incorrect SpA diagnoses. By promoting this model across diverse health care settings, we anticipate a significant improvement in SpA management, culminating in enhanced patient outcomes and a reduced overall burden of the disease. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57001.

"Turn-on" and pinhole-free ultrathin core-shell Au@SiO2 nanoparticle-based metal-enhanced fluorescent (MEF) chemodosimeter for Hg2.

This study reports a metal-enhanced fluorescence chemodosimeter for highly sensitive detection of Hg2+ ions. Silica-coated Au nanoparticles (Au@SiO2 NPs) with a pinhole-free 4-5 nm shell were synthesized and functionalized with a monolayer of turn-on fluorescent probes. Compared to other organic fluorescent probes suffering from poor biocompatibility and detection limits, this design of a monolayer of turn-on fluorescent probes immobilized on the Au@SiO2 NPs with a pinhole-free 4-5 nm shell avoids fluorescence quenching and allows the fluorescent probe within the field of the inner Au NPs to experience metal-enhanced fluorescence. With this design, the chemodosimeter permits fluorescence emission in the presence of Hg2+ ions, because they trigger the ring-opening reaction of the fluorescent probe immobilized on the Au@SiO2 NPs. Additionally, the fluorescent probe is distanced by the thin SiO2 shell from directly attaching to the metallic Au NPs, which not only avoids fluorescence quenching but allows the fluorescent probe within the long-ranged field of the inner Au NPs to experience metal-enhanced fluorescence. As a result, the detection limit for the chemodosimeter can reach up to 5.0 × 10-11 M, nearly two orders of magnitude higher than that achieved for the free fluorescent probe. We also demonstrate the acquisition of images of Hg2+ in HTC116 cells and zebrafish using a simple fluorescence confocal imaging technique. The fluorescence response results for HTC116 cells and zebrafish show that the probes can permeate into cells and organisms. Considering the availability of the many organic fluorescent probes that have been designed, the current designed metal-enhanced fluorescence chemodosimeter holds great potential for fluorescence detection of diverse species and fluorescence imaging.

Non-Pharmacological Strategies for Managing Sarcopenia in Chronic Diseases.

This article focuses on a range of non-pharmacological strategies for managing sarcopenia in chronic diseases, including exercise, dietary supplements, traditional Chinese exercise, intestinal microecology, and rehabilitation therapies for individuals with limited limb movement. By analyzing multiple studies, the article aims to summarize the available evidence to manage sarcopenia in individuals with chronic diseases. The results strongly emphasize the role of resistance training in addressing chronic diseases and secondary sarcopenia. Maintaining the appropriate frequency and intensity of resistance training can help prevent muscle atrophy and effectively reduce inflammation. Although aerobic exercise has limited ability to improve skeletal muscle mass, it does have some positive effects on physical function. Building upon this, the article explores the potential benefits of combined training approaches, highlighting their helpfulness for overall quality of life. Additionally, the article also highlights the importance of dietary supplements in combating muscle atrophy in chronic diseases. It focuses on the importance of protein intake, supplements rich in essential amino acids and omega-3, as well as sufficient vitamin D to prevent muscle atrophy. Combining exercise with dietary supplements appears to be an effective strategy for preventing sarcopenia, although the optimal dosage and type of supplement remain unclear. Furthermore, the article explores the potential benefits of intestinal microecology in sarcopenia. Probiotics, prebiotics, and bacterial products are suggested as new treatment options for sarcopenia. Additionally, emerging therapies such as whole body vibration training, blood flow restriction, and electrical stimulation show promise in treating sarcopenia with limited limb movement. Overall, this article provides valuable insights into non-pharmacological strategies for managing sarcopenia in individuals with chronic diseases. It emphasizes the importance of a holistic and integrated approach that incorporates exercise, nutrition, and multidisciplinary interventions, which have the potential to promote health in the elderly population. Future research should prioritize high-quality randomized controlled trials and utilize wearable devices, smartphone applications, and other advanced surveillance methods to investigate the most effective intervention strategies for sarcopenia associated with different chronic diseases.

Geographical traceability of flavor compounds in Chinese mitten crab (Eriocheir sinensis): Implications for quality differentiation, authenticity assessment, and mechanism research.

Geographical traceability plays a crucial role in ensuring quality assurance, brand establishment, and the sustainable development of the crab industry. In this study, we examined the possibility of using gas chromatography-ion mobility spectrometry with multivariate statistical authenticity analysis to identify the origin of crabs from five sites downstream of the Yangtze River. Significant variations were observed in the levels of alcoholic flavor compounds in the hepatopancreas and muscles of crabs from different geographical locations, and a support vector machine exhibited discriminant ability with 100% accuracy. These flavor variations exhibited significant correlations with the types and concentrations of elements within the crabs, as well as with free amino acids. This study offers a practical approach for determining the geographical traceability of Chinese mitten crabs and elucidates the role of elements in flavor modulation, thereby providing innovative strategies to enhance the efficiency of crab farming.

The prevalence of sarcopenia in spondyloarthritis patients: a meta-analysis.

BACKGROUND: Spondyloarthritis (SpA) is a chronic inflammatory disorder that affects sacroiliac joints and spine, resulting in substantial disability. Sarcopenia, characterized by the loss of muscle mass and function, is a prevalent comorbidity in various chronic diseases. However, the exact prevalence of sarcopenia in SpA patients remains uncertain. The objective of this study is to conduct a systematic review and meta-analysis of the available literature to determine the prevalence of sarcopenia in SpA. METHODS: A comprehensive search was conducted in EMBASE, MEDLINE, WEB OF SCIENCE, and COCHRANE databases to identify relevant studies published up to 2023. Studies investigating the prevalence of sarcopenia in SpA patients were included. Data on study characteristics, participant demographics, diagnostic criteria for sarcopenia, and prevalence rates were extracted. Meta-analysis was performed using a random-effects model to estimate the overall prevalence of sarcopenia in SpA patients. RESULTS: A total of 16 studies that met the inclusion criteria were included in the systematic review. These studies encompassed a combined sample size of 999 patients with SpA. The meta-analysis findings revealed that the overall prevalence of sarcopenia in SpA patients was 25.0% (95% confidence interval: 0.127 to 0.352). Furthermore, the prevalence of presarcopenia and severe sarcopenia was found to be 21.0% and 8.7%, respectively. Subgroup analysis was conducted to examine different diagnostic criteria, subtypes, and sex of SpA in relation to sarcopenia. CONCLUSION: This systematic review and meta-analysis provide a comprehensive overview of the prevalence of sarcopenia in SpA patients. The findings suggest a high prevalence of sarcopenia in SpA patients, emphasizing the need for targeted interventions to prevent and manage sarcopenia. And further research is needed to explore the underlying mechanisms and potential therapeutic strategies for sarcopenia in SpA.

Postoperative Prognostic Nutritional Index and Fibrinogen Could Well Predict Poor Prognosis of Acute Type A Aortic Dissection Patients After Surgery.

INTRODUCTION: Inflammatory and immunological factors play pivotal roles in the prognosis of acute type A aortic dissection. We aimed to evaluate the prognostic values of immune-inflammatory parameters in acute type A aortic dissection patients after surgery. METHODS: A total of 127 acute type A aortic dissection patients were included. Perioperative clinical data were collected through the hospital's information system. The outcomes studied were delayed extubation, reintubation, and 30-day mortality. Multivariate logistic regression analysis and receiver operating characteristic analysis were used to screen the risk factors of poor prognosis. RESULTS: Of all participants, 94 were male, and mean age was 51.95±11.89 years. The postoperative prognostic nutritional indexes were lower in delayed extubation patients, reintubation patients, and patients who died within 30 days. After multivariate regression analysis, the postoperative prognostic nutritional index was a protective parameter of poor prognosis. The odds ratios (95% confidence interval) of postoperative prognostic nutritional index were 0.898 (0.815, 0.989) for delayed extubation and 0.792 (0.696, 0.901) for 30-day mortality. Low postoperative fibrinogen could also well predict poor clinical outcomes. The odds ratios (95% confidence interval) of postoperative fibrinogen were 0.487 (0.291, 0.813) for delayed extubation, 0.292 (0.124, 0.687) for reintubation, and 0.249 (0.093, 0.669) for 30-day mortality. CONCLUSION: Postoperative prognostic nutritional index and postoperative fibrinogen could be two promising markers to identify poor prognosis of acute type A aortic dissection patients after surgery.

Chlorella alleviates the intestinal damage of tilapia caused by microplastics.

Polyethylene microplastics (MPs) of the different sizes may result in different response in fish. Studies showed microorganisms adhered to the surface of MPs have toxicological effect. Juveniles tilapia (Oreochromis niloticus, n = 600, 26.5 ± 0.6 g) were dispersed into six groups: the control group (A), 75 nm MP exposed group (B), 7.5 µm group (C) and 750 (D) µm group, 75 nm + 7.5 µm+750 µm group (E) and 75 nm + Chlorella vulgaris group (F), and exposed for 10 and 14 days. The intestinal histopathological change, enzymic activities, and the integrated "omics" workflows containing transcriptomics, proteomics, microbiota and metabolomes, have been performed in tilapia. Results showed that MPs were distributed on the surface of goblet cells, Chlorella group had severe villi fusion without something like intestinal damage, as in other MPs groups. The intestinal Total Cholesterol (TC, together with group E) and Tumor Necrosis Factor α (TNFα, except for group B) contents in group F were significantly increased, cytochrome p450 1a1 (EROD, group B and E) significantly increased, adenosine triphosphate (ATP), lipoprotein lipase (LPL) and caspase 3 (except group B) also significantly increased at 14 d. At 14 days, group E saw considerably higher regulation of the actin cytoskeleton, focal adhesion, insulin signaling pathway, and AGE-RAGE signaling pathway in diabetes complications. Whereas, chlorella enhanced the focal adhesion, cytokine-cytokine receptor interaction, and MAPK signaling pathways. PPAR signaling pathway has been extremely significantly enriched via the proteomics method. Candidatus latescibacteria, C. uhrbacteria, C. abyssubacteria, C. cryosericota significantly decreased caused by MPs of different particle sizes. Carboxylic acids and derivatives, indoles and derivatives, organooxygen compounds, fatty acyls and organooxygen compounds significantly increased with long-term duration, especially PPAR signaling pathway. MPs had a size-dependent long-term effect on histopathological change, gene and protein expression, and gut microbial metabolites, while chlorella alleviates the intestinal histopathological damage via the integrated "omics" workflows.

Involvement of reactive oxygen species (ROS) in the hepatopancreatic cytotoxicity, oxidative stress, and apoptosis induced by microcystin-LR in Eriocheir sinensis.

There is limited knowledge about the toxicity of Microcystin-LR (MC-LR) in crustaceans, despite its high toxicity to aquatic organisms. This research aimed to explore the effects of MC-LR on cytotoxicity, oxidative stress, and apoptosis in the hepatopancreas of Eriocheir sinensis, as well as elucidate the involvement of reactive oxygen species (ROS) and potential mechanisms of toxicity. In vivo and in vitro exposures of crabs to MC-LR and N-acetylcysteine (NAC) were performed, followed by assessments of cell morphology, viability, tissue pathology, biochemical indicators, gene expression, and hepatopancreatic transcriptome. Results revealed that MC-LR facilitated the entry of the MC-LR transporter oatp3a into hepatopancreatic cells, leading to upregulated expression of phase I detoxification enzyme genes (cyp4c, cyp2e1, and cyp3) and downregulated the phase II enzyme genes (gst1, gpx, gsr2, gclc, and nqo1), resulting in increased ROS levels and cytotoxic effects. MC-LR exhibited cytotoxicity, reducing cell viability and inducing abnormal nuclear morphology with a 48 h-IC50 value of approximately 120 µm. MC-LR exposure caused biochemical changes indicative of oxidative stress damage and evident hepatopancreatic lesions. Additionally, MC-LR exposure regulated the levels of bax and bcl-2 expression, activating caspase 3 and 6 to induce cell apoptosis. Intervention with NAC attenuated MC-LR-induced ROS production and associated toxic effects. Transcriptome analysis revealed enrichment of differentially expressed genes in pathways related to cytochrome P450-mediated xenobiotic metabolism and the FoxO signaling pathway. These findings shed light on the potential mechanisms underlying MC-LR toxicity and provide valuable references for further research and conservation efforts regarding the health of aquatic animals.

Postoperative Prognostic Nutritional Index and Fibrinogen Could Well Predict Poor Prognosis of Acute Type A Aortic Dissection Patients After Surgery

ABSTRACT Introduction: Inflammatory and immunological factors play pivotal roles in the prognosis of acute type A aortic dissection. We aimed to evaluate the prognostic values of immune-inflammatory parameters in acute type A aortic dissection patients after surgery. Methods: A total of 127 acute type A aortic dissection patients were included. Perioperative clinical data were collected through the hospital's information system. The outcomes studied were delayed extubation, reintubation, and 30-day mortality. Multivariate logistic regression analysis and receiver operating characteristic analysis were used to screen the risk factors of poor prognosis. Results: Of all participants, 94 were male, and mean age was 51.95±11.89 years. The postoperative prognostic nutritional indexes were lower in delayed extubation patients, reintubation patients, and patients who died within 30 days. After multivariate regression analysis, the postoperative prognostic nutritional index was a protective parameter of poor prognosis. The odds ratios (95% confidence interval) of postoperative prognostic nutritional index were 0.898 (0.815, 0.989) for delayed extubation and 0.792 (0.696, 0.901) for 30-day mortality. Low postoperative fibrinogen could also well predict poor clinical outcomes. The odds ratios (95% confidence interval) of postoperative fibrinogen were 0.487 (0.291, 0.813) for delayed extubation, 0.292 (0.124, 0.687) for reintubation, and 0.249 (0.093, 0.669) for 30-day mortality. Conclusion: Postoperative prognostic nutritional index and postoperative fibrinogen could be two promising markers to identify poor prognosis of acute type A aortic dissection patients after surgery.

Efficient and Homogeneous Carbonitriding of High-Entropy Alloys by a Mechanochemical Process for Obtaining Coordinated Electromagnetic Matching.

Optimizing the impedance matching via electromagnetic adjustment is considered an effective strategy to accomplish exceptional electromagnetic wave absorption (EMA) performance. Here, we report an efficient and green process to obtain the carbonitriding FeCoNiCr high-entropy alloys (HEAs) with flake-shaped morphology by using organic cyanide (Dicyandiamide, C2H4N4) as nitrogen and carbon sources. The carbonitriding effects on the phase structure, magnetic properties, mechanical hardness, corrosion resistance, high-temperature oxidation resistance, and EMA performances were investigated systematically. The carbonitriding process optimized the impedance match by decreasing the dielectric constant via introducing the nonmetallic C and N. The #CN10 sample exhibited outstanding EMA performances with a minimum reflection loss of -32.3 dB at 7.89 GHz and a broad effective bandwidth of 4.46 GHz, which covered the majority of X-band. In addition, the carbonitriding FeCoNiCr HEAs had great mechanical properties, excellent corrosion resistance, and high-temperature oxidation resistance, indicating excellent adaptability to harsh environments as well as good EMA performances. This work provides a new idea for the preparation and design of carbonitriding EMA materials.

Systematic review and meta-analysis of segmentectomy vs. lobectomy for stage IA non-small cell lung cancer.

Background: Whether segmentectomy is appropriate for stage IA non-small cell lung cancer (NSCLC), especially for stage IA NSCLC with a tumor size of 2-3 cm, remains controversial. Thus, we conducted this meta-analysis to compare segmentectomy and lobectomy for stage IA NSCLC with a tumor size of 2-3 cm and IA ≤2 cm NSCLC. Methods: A systematic screening of online databases (PubMed, Embase, Web of Science, and Cochrane Library) was conducted regarding the terms of perioperative outcomes, overall survival (OS), recurrence-free survival (RFS), and disease-free survival (DFS). The inverse-variance and Mantel-Haenszel approaches were used to pool effect sizes for survival outcomes and perioperative outcomes. Results: A total of 10 articles were included in the analysis. The perioperative morbidity [risk ratio (RR): 0.90, P=0.10], mortality (RR: 0.94, P=0.84), intraoperative blood loss [mean difference (MD): 3.07, P=0.86] and operative time (MD: 18.99, P=0.13) were comparable between the segmentectomy and lobectomy groups. The number of lymph nodes harvested was statistically less in segmentectomy than in lobectomy (MD: -5.71, P=0.02). In stage IA patients with a tumor size of 2-3 cm, lobectomy showed superior survival outcomes compared to segmentectomy, with a pooled hazard ratio (HR) of 1.39 (P=0.01) for OS and 1.38 (P=0.06) for RFS or DFS. In stage IA ≤2 cm, lobectomy and segmentectomy had comparable survival outcomes with pooled HRs of 1.18 (P=0.29) for OS and 1.18 (P=0.12) for RFS or DFS. Conclusions: When a patient is in stage IA and the tumor size is less than 2 cm, segmentectomy should be performed. If the tumor size is between 2 and 3 cm, lobectomy is recommended.

Copper Catalyzed Defluoroarylation of gem-Difluoroallenes to Allenyl Monofluorides with Aryl Boronic Esters.

Few studies have been performed on allenyl monofluorides, especially on aryl-substituted frames, due to concerns about their stability. Here we report a copper-catalyzed regioselective synthesis of such structures with inexpensive and accessible aryl boronic esters under mild conditions. Arylated allenyl monofluorides were stable enough to be isolated and easily converted to various other fluorine-containing blueprints. Preliminary asymmetric attempts demonstrate that the reaction could proceed via a selective ß-fluorine elimination process.

A practical "preTACs-cytoblot" platform accelerates the streamlined development of PROTAC-based protein degraders.

With the growing importance of PROTAC-mediated protein degradation in drug discovery, robust synthetic methodologies and rapid screening assays are urgently needed. By harnessing the improved alkene hydroazidation reaction, we developed a novel strategy to introduce azido groups into the linker-E3 ligand conjugates and effectively created a range of prepacked terminal azide-labeled "preTACs" as PROTAC toolkit building blocks. Moreover, we demonstrated that preTACs are ready to conjugate to ligands targeting a protein of interest to generate libraries of chimeric degraders, which are subsequently screened for effective protein degradation directly from cultured cells with a cytoblot assay. Our study exemplifies that this practical "preTACs-cytoblot" platform allows efficient PROTAC assembly and rapid activity assessments. It may help industrial and academic investigators to accelerate their streamlined development of PROTAC-based protein degraders.

Transient high salt intake causes epigenetic changes and leads to persistent inflammatory activation to produce "salt memory".

Transient high salt intake causes a sustained increase in blood pressure (BP) even after returning to a normal-salt diet, a phenomenon known as "salt memory." However, the molecular mechanisms of this phenomenon remain to be elucidated. Dahl salt-sensitive (SS) rats were fed a high-salt (8% NaCl) or high-salt diet and treated with drugs for 8 to 16 weeks and then returned to a normal-salt diet for 3 months. This study investigated the molecular mechanisms of salt memory and its mediation of SS hypertension and renal damage. We show that transient high salt intake caused persistent elevation of BP and exacerbation of kidney damage in Dahl SS rats even after returning to a normal-salt diet. Both epigenetic changes and inflammatory activation also persisted after resumption of a normal diet. Arterial BP, renal injury and the inflammatory response returned to normal levels in rats administered mycophenolate mofetil (MMF) during the 8-week period of high salt intake, resulting in the disappearance of salt memory. However, the vasodilator hydralazine did not ameliorate kidney damage or inflammatory activation, although it decreased BP to control levels. Transient high salt intake increased histone 3 lysine 4 monomethylation (H3K4me1) levels at the nuclear factor κB (NF-κB) subunit p65 promoter in SS rats, promoting p65 gene transcription and NF-κB activation and further leading to a series of inflammatory responses. Our findings demonstrate that transient high salt-induced epigenetic changes and persistent inflammatory activation play important roles in salt memory and its mediation of SS hypertension and renal damage.

Delayed Polarization Saturation Induced Superior Energy Storage Capability of BiFeO3 -Based Ceramics Via Introduction of Non-Isovalent Ions.

Electrostatic capacitors are emerging as a highly promising technology for large-scale energy storage applications. However, it remains a significant challenge to improve their energy densities. Here, an effective strategy of introducing non-isovalent ions into the BiFeO3 -based (BFO) ceramic to improve energy storage capability via delaying polarization saturation is demonstrated. Accordingly, an ultra-high energy density of up to 7.4 J cm-3 and high efficiency ≈ 81% at 680 kV m-1 are realized, which is one of the best energy storage performances recorded for BFO-based ceramics. The outstanding comprehensive energy storage performance is attributed to inhibiting the polarization hysteresis resulting from generation ergodic relaxor zone and random field, and generating highly-delayed polarization saturation with continuously-increased polarization magnitudes with the electric field of supercritical evolution. The contributions demonstrate that delaying the polarization saturation is a consideration for designing the next generation of lead-free dielectric materials with ultra-high energy storage performance.