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Background and Purpose: Activation of the renin‐angiotensin system, as a hallmark of hypertension and chronic kidney diseases (CKD) is the key pathophysiological factor contributing to the progression of tubulointerstitial fibrosis. LIM and senescent cell antigen‐like domains protein 1 (LIMS1) plays an essential role in controlling of cell behaviour through the formation of complexes with other proteins. Here, the function and regulation of LIMS1 in angiotensin II (Ang II)‐induced hypertension and tubulointerstitial fibrosis was investigated. Experimental Approach: C57BL/6 mice were treated with Ang II to induce tubulointerstitial fibrosis. Hypoxia‐inducible factor‐1α (HIF‐1α) renal tubular‐specific knockout mice or LIMS1 knockdown AAV was used to investigate their effects on Ang II‐induced renal interstitial fibrosis. In vitro, HIF‐1α or LIMS1 was knocked down or overexpressed in HK2 cells after exposure to Ang II. Key Results: Increased expression of tubular LIMS1 was observed in human kidney with hypertensive nephropathy and in murine kidney from Ang II‐induced hypertension model. Tubular‐specific knockdown of LIMS1 ameliorated Ang II‐induced tubulointerstitial fibrosis in mice. Furthermore, we demonstrated that LIMS1 was transcriptionally regulated by HIF‐1α in tubular cells and that tubular HIF‐1α knockout ameliorates LIMS1‐mediated tubulointerstitial fibrosis. In addition, LIMS1 promotes Ang II‐induced tubulointerstitial fibrosis by interacting with vimentin. Conclusion and Implications: We conclude that HIF‐1α transcriptionally regulated LIMS1 plays a central role in Ang II‐induced tubulointerstitial fibrosis through interacting with vimentin. Our finding represents a new insight into the mechanism of Ang II‐induced tubulointerstitial fibrosis and provides a novel therapeutic target for progression of CKD. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is highly prevalent worldwide, and its global burden is substantial and growing. CKD displays a number of features of accelerated senescence. Tubular cell senescence is a common biological process that contributes to CKD progression. Tubulointerstitial inflammation is a driver of tubular cell senescence and a common characteristic of CKD. However, the mechanism by which the interstitial inflammation drives tubular cell senescence remains unclear. This paper aims to explore the role of exosomal miRNAs derived from macrophages in the development of tubular cell senescence. Methods: Among the identified inflammation-related miRNAs, miR-155 is considered to be one of the most important miRNAs involved in the inflammatory response. Macrophages, the primary immune cells that mediate inflammatory processes, contain a high abundance of miR-155 in their released exosomes. We assessed the potential role of miR-155 in tubular cell senescence and renal fibrosis. We subjected miR-155−/− mice and wild-type controls, as well as tubular epithelial cells (TECs), to angiotensin II (AngII)-induced kidney injury. We assessed kidney function and injury using standard techniques. TECs were evaluated for cell senescence and telomere dysfunction in vivo and in vitro. Telomeres were measured by the fluorescence in situ hybridization. Results: Compared with normal controls, miR-155 was up-regulated in proximal renal tubule cells in CKD patients and mouse models of CKD. Moreover, the expression of miR-155 was positively correlated with the extent of renal fibrosis, eGFR decline and p16INK4A expression. The overexpression of miR-155 exacerbated tubular senescence, evidenced by increased detection of p16INK4A/p21expression and senescence-associated β-galactosidase activity. Notably, miR-155 knockout attenuates renal fibrosis and tubule cell senescence in vivo. Interestingly, once released, macrophages-derived exosomal miR-155 was internalized by TECs, leading to telomere shortening and dysfunction through targeting TRF1. A dual-luciferase reporter assay confirmed that TRF1 was the direct target of miR-155. Thus, our study clearly demonstrates that exosomal miR-155 may mediate communication between macrophages and TECs, subsequently inducing telomere dysfunction and senescence in TECs. Conclusions: Our work suggests a new mechanism by which macrophage exosomes are involved in the development of tubule senescence and renal fibrosis, in part by delivering miR-155 to target TRF1 to promote telomere dysfunction. Our study may provide novel strategies for the treatment of AngII-induced kidney injury. [ABSTRACT FROM AUTHOR]

The article introduces a novel machine learning-based prediction model for identifying moderate to severe acute kidney injury (AKI) in heart failure patients. Topics discussed include the development and validation of the model using XGBoost, its performance compared to other models, and the importance of feature selection for prediction accuracy.

Exosomal microRNAs (miRNAs) play a pivotal role in intercellular communication, regulating gene expression in target cells, and hold significant promise as cancer biomarkers for early detection and screening. However, achieving precise and viable detection of exosomal miRNAs remains a challenge. This paper proposes an all-in-one detection strategy for breast cancer-derived exosomal miRNA-21 on a pen-based paper chip (PPC). The PPC is constructed using a modified automatic pen and lateral flow assay (LFA), which results in a cost-effective fabrication process. The user only needs to add the sample and trigger the top of the self-contained PPC after a period of time to complete the entire detection process. To enhance the sensitivity of exosomal miRNA testing, an enzyme-free catalyzed hairpin assembly (CHA) is further introduced, enabling highly sensitive detection of miRNA-21 with a limit of detection (LOD) of 25 fmol. Additionally, the detection of miRNAs in differentially-expressed cells and clinical samples has also been successfully achieved with high specificity. Overall, the proposed PPC provides an effective tool for detecting early cancer, monitoring diseases, and establishing point of care testing (POCT). [ABSTRACT FROM AUTHOR]

Numerous reported bioinspired osmotic energy conversion systems employing cation‐/anion‐selective membranes and solutions with different salinity are actually far from the biological counterpart. The iso‐osmotic power generator with the specific ionic permselective channels (e.g. K+ or Na+ channels) which just allow specific ions to get across and iso‐osmotic solutions still remain challenges. Inspired by nature, we report a bioinspired K+‐channel by employing a K+ selective ligand, 1,1,1‐tris{[(2′‐benzylaminoformyl)phenoxy]methyl}ethane (BMP) and graphene oxide membrane. Specifically, the K+ and Na+ selectivity of the prepared system could reach up to ≈17.8, and the molecular dynamics simulation revealed that the excellent permselectivity of K+ mainly stemmed from the formed suitable channel size. Thus, we assembled the K+‐selective iso‐osmotic power generator (KSIPG) with the power density up to ≈15.1 mW/m2 between equal concentration solutions, which is higher than traditional charge‐selective osmotic power generator (CSOPG). The proposed strategy has well shown the realizable approach to construct single‐ion selective channels‐based highly efficient iso‐osmotic energy conversion systems and would surely inspire new applications in other fields, including self‐powered systems and medical materials, etc. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer (OC) is one of the most common gynecological tumors with high morbidity and mortality. Altered serum N-glycome has been observed in many diseases, while the association between serum protein N-glycosylation and OC progression remains unclear, particularly for the onset of carcinogenesis from benign neoplasms to cancer. Methods: Herein, a mass spectrometry based high-throughput technique was applied to characterize serum N-glycome profile in individuals with healthy controls, benign neoplasms and different stages of OC. To elucidate the alterations of glycan features in OC progression, an orthogonal strategy with lectin-based ELISA was performed. Results: It was observed that the initiation and development of OC was associated with increased high-mannosylationand agalactosylation, concurrently with decreased total sialylation of serum, each of which gained at least moderately accurate merits. The most important individual N-glycans in each glycan group was H7N2, H3N5 and H5N4S2F1, respectively. Notably, serum N-glycome could be used to accurately discriminate OC patients from benign cohorts, with a comparable or even higher diagnostic score compared to CA125 and HE4. Furthermore, bioinformatics analysis based discriminative model verified the diagnostic performance of serum N-glycome for OC in two independent sets. Conclusions: These findings demonstrated the great potential of serum N-glycome for OC diagnosis and precancerous lesion prediction, paving a new way for OC screening and monitoring. [ABSTRACT FROM AUTHOR]

Improving energy efficiency is crucial for China's power industry to meet global energy conservation and emission reduction goals. The rapid development of photovoltaic (PV) and hydropower has greatly assisted in the construction of China's novel power system. The stochastic characteristics of PV power generation pose significant challenges to the reliable and economical scheduling of power systems. In fact, the cascade hydropower station can effectively address the issue. To fully utilize the advantages of hydropower, this paper proposes a bi-layer scheduling optimization model for the cascade hydro-PV complementary system considering power market. The upper-layer model simultaneously maximizes the benefit and minimizes the output volatility of the complementary system. The lower-layer model carries out market clearing with the objective of social cost. Besides, PV uncertainty and market price volatility are considered in the decision-making process for power market transactions. To solve the bi-layer model, a novel meta-heuristic algorithm (geometric mean optimizer) is applied, demonstrating excellent performance compared to similar methods. For the complementary system, the results show that its total power output can be improved, and its output volatility can be effectively alleviated. [ABSTRACT FROM AUTHOR]

Background The discovery of phospholipase A2 receptor (PLA2R) and its antibody (aPLA2Rab) has paved the way for diagnosing PLA2R-associated membranous nephropathy (PLA2R-MN) with a high specificity of 98%. However, the sensitivity was only 40% to 83.9%, and there is ongoing discussion around determining the optimal threshold for diagnosis. Recent advancements in the use of exosomes, a novel form of "liquid biopsy," have shown great promise in identifying markers for various medical conditions. Methods Protein mass spectrometry and western blot were applied to verify the existence of PLA2R antigen in the urine exosome. We then evaluated the efficacy of urinary exosomal PLA2R antigen alone or combined with serum aPLA2Rab level to diagnose PLA2R-MN. Results The urinary exosomes contained a high abundance of PLA2R antigen as evidenced by protein mass spectrometry and western blot in 85 PLA2R-MN patients vs the disease controls (14 secondary MN patients, 22 non-MN patients and 4 PLA2R-negative MN patients) and 20 healthy controls. Of note, urinary exosomal PLA2R antigen abundance also had a good consistency with the PLA2R antigen level in the renal specimens of PLA2R-MN patients. The sensitivity of urinary exosomal PLA2R for diagnosing PLA2R-MN reached 95.4%, whereas the specificity was 63.3%. Combining detection of the urinary exosomal PLA2R and serum aPLA2Rab could develop a more sensitive diagnostic method for PLA2R-MN, especially for patients with serum aPLA2Rab ranging from 2 to 20 RU/mL. Conclusions Measurement of urinary exosomal PLA2R could be a sensitive method for the diagnosis of PLA2R-MN. [ABSTRACT FROM AUTHOR]

Variations are present in common clinical practices regarding best practice in managing hyperkalaemia (HK), there is therefore a need to establish a multi-specialty approach to optimal rennin-angiotension-aldosterone system inhibitors (RAASi) usage and HK management in patients with chronic kidney disease (CKD) & heart failure (HF). This study aimed to establish a multi-speciality approach to the optimal use of RAASi and the management of HK in patients with CKD and HF. A steering expert group of cardiology and nephrology experts across China were convened to discuss challenges to HK management through a nominal group technique. The group then created a list of 41 statements for a consensus questionnaire, which was distributed for a further survey in extended panel group of cardiologists and nephrologists across China. Consensus was assessed using a modified Delphi technique, with agreement defined as "strong" (≥75% and <90%) and "very strong" (≥90%). The steering group, data collection, and analysis were aided by an independent facilitator. A total of 150 responses from 21 provinces across China were recruited in the survey. Respondents were comprised of an even split (n =75, 50%) between cardiologists and nephrologists. All 41 statements achieved the 75% consensus agreement threshold, of which 27 statements attained very strong consensus (≥90% agreement) and 14 attained strong consensus (agreement between 75% and 90%). Based on the agreement levels from respondents, the steering group agreed a set of recommendations intended to improve patient outcomes in the use of RAASi therapy and HK management in China. [ABSTRACT FROM AUTHOR]

In microbiological research, traditional methods for bacterial screening and antibiotic susceptibility testing are resource‐intensive. Microfluidics offers an efficient alternative with rapid results and minimal sample consumption, but the demand for cost‐effective, user‐friendly platforms persists in communities and hospitals. Inspired by the Magdeburg hemispheres, the strategy adapts to local conditions, leveraging omnipresent atmospheric pressure for self‐sealing of Rotation‐SlipChip (RSC) equipped with a 3D circular Christmas tree‐like microfluidic concentration gradient generator. This innovative approach provides an accessible and adaptable platform for microbiological research and testing in diverse settings. The RSC can avoid leakage concerns during multiple concentration gradient generation, chip‐rotating, and final long‐term incubation reaction (≥24 h). Furtherly, RSC subtypes adapted to different reactions can be fabricated in less than 15 min with cost less than $1, the result can be read through designated observational windows by naked‐eye. Moreover, the RSC demonstrates its capability for evaluating bacterial biomarker activity, enabling the rapid assessment of β‐galactosidase concentration and enzyme activity within 30 min, and the limit of detection can be reduced by 10‐fold. It also rapidly determines the minimum antibiotic inhibitory concentration and antibiotic combined medications results within 4 h. Overall, these low‐cost and user‐friendly RSC make them invaluable tools in determinations at previously impractical environment. [ABSTRACT FROM AUTHOR]

Discs and numerous other consumer products have been developed for point of care testing (POCT) to replace traditional large and expensive biochemical devices in certain scenarios. Herein, we propose a drip-dry strategy (2D strategy) assisted Blu-ray disc (BD) biosensor, termed BDB, for rapid and portable POCT within 30 min with the cost of a single test < $1. The platform utilizes the covered area formed by the deposition of the substance to be measured on the activated BD surface after the evaporation of water and realizes the quantitative detection of the target through the error readout of free disc quality diagnosis software. As a proof of concept, we first demonstrated the feasibility of direct quantitative detection of substances in solution in a single system through the detection of pure proteins avoiding colorimetric reagent used in traditional optical detection. For the complex mixed systems, we then innovatively utilize the principle that soluble targets promote/inhibit the dissolution of insoluble precipitates to achieve specific detection of targets and successfully apply BDB to the indirect quantitative detection of glutathione (GSH) with LOD of 0.447 mM in the range of 2-16 mM and organophosphorus pesticides (OPs) with LOD of 2.122 × 10 -7 M in the range of 1.289 × 10 -7 -1.289 × 10 -4 M. The BDB is widely applicable, easy to operate, and less time-consuming, which is anticipated to provide an alternative method for early, on-site detection or screening.