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Abstract Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults and is associated with high rates of end-stage renal disease. Early detection and precise interventions are crucial for improving patient prognosis and quality of life. However, the current diagnosis primarily relies on renal biopsies and traditional biomarkers, which have limitations. Additionally, targeted therapeutic strategies are lacking. Exosomes, small vesicles that facilitate intercellular communication, have emerged as potential noninvasive diagnostic markers due to their stability, diverse cargo, and rapid detectability. They also hold promise as carriers for gene and drug delivery, presenting innovative opportunities in renal disease prognosis and treatment. However, research on exosomes in the context of idiopathic membranous nephropathy (IMN) remains limited, with a focus on exploring urinary exosomes as IMN markers. In this review, we summarize the current status of MN diagnosis and treatment, highlight the fundamental characteristics of exosomes, and discuss recent advancements in their application to IMN diagnosis and therapy. We provide insights into the clinical prospects of exosomes in IMN and acknowledge potential challenges. This article aims to offer forward-looking insights into the future of exosome-mediated IMN diagnosis and treatment, indicating a revolutionary transformation in this field. Graphical Abstract

Abstract Background Numerous studies have been conducted to investigate the relationship between ABO and Rhesus (Rh) blood groups and various health outcomes. However, a comprehensive evaluation of the robustness of these associations is still lacking. Methods We searched PubMed, Web of Science, Embase, Scopus, Cochrane, and several regional databases from their inception until Feb 16, 2024, with the aim of identifying systematic reviews with meta-analyses of observational studies exploring associations between ABO and Rh blood groups and diverse health outcomes. For each association, we calculated the summary effect sizes, corresponding 95% confidence intervals, 95% prediction interval, heterogeneity, small-study effect, and evaluation of excess significance bias. The evidence was evaluated on a grading scale that ranged from convincing (Class I) to weak (Class IV). We assessed the certainty of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation criteria (GRADE). We also evaluated the methodological quality of included studies using the A Measurement Tool to Assess Systematic Reviews (AMSTAR). AMSTAR contains 11 items, which were scored as high (8–11), moderate (4–7), and low (0–3) quality. We have gotten the registration for protocol on the PROSPERO database (CRD42023409547). Results The current umbrella review included 51 systematic reviews with meta-analysis articles with 270 associations. We re-calculated each association and found only one convincing evidence (Class I) for an association between blood group B and type 2 diabetes mellitus risk compared with the non-B blood group. It had a summary odds ratio of 1.28 (95% confidence interval: 1.17, 1.40), was supported by 6870 cases with small heterogeneity (I 2 = 13%) and 95% prediction intervals excluding the null value, and without hints of small-study effects (P for Egger’s test > 0.10, but the largest study effect was not more conservative than the summary effect size) or excess of significance (P

Introduction: The available approved anticancer drugs for Chinese patients are relatively limited because of China's low participation rate in international clinical trials. Therefore, a focus on approved anti–programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) drugs in China is needed. This study aims to assess the heterogeneity of anti–PD-1/PD-L1 antibodies manufactured in China (domestic PD-1/PD-L1) and overseas (imported PD-1/PD-L1) when combined with chemotherapy as the first-line treatment of NSCLC. Methods: A systematic search was performed using PubMed, EMBASE, and Cochrane Library of publications up to July 13, 2023. Meta-analysis was applied to compare the efficacy and safety profile between anti–PD-1/PD-L1 antibodies plus chemotherapy (PD-1/PD-L1+Chemo) and chemotherapy alone using STATA software. Pooled hazard ratios for progression-free survival and overall survival, odds ratios for objective response rate, and incidence rate of grade greater than or equal to three treatment-related adverse events with 95% confidence intervals were calculated in the domestic group and imported group by a random-effects model, and the heterogeneity between the two estimates was assessed. Results: There were 14 eligible clinical studies with a total of 3951 patients involved in this analysis, including eight studies of domestic PD-1/PD-L1+Chemo and six studies of imported PD-1/PD-L1+Chemo. The study revealed that there was no significant difference between domestic and imported PD-1/PD-L1+Chemo in overall survival (p = 0.80), progression-free survival (p = 0.53), and incidence rate of grade greater than or equal to three treatment-related adverse events (p = 0.10). Nevertheless, the objective response rate of imported PD-1/PD-L1+Chemo was significantly higher than that of domestic PD-1/PD-L1+Chemo (p = 0.03). Conclusions: Domestic anti–PD-1/PD-L1 antibodies plus chemotherapy were found to have comparable efficacy and safety to those combined with imported anti–PD-1/PD-L1 antibodies based on current evidence.

Background: Elderly patients undergoing surgery are prone to cognitive decline known as perioperative neurocognitive disorders (PND). Several studies have shown that the microglial activation and the decrease of short-chain fatty acids (SCFAs) in gut induced by surgery may be related to the pathogenesis of PND. The purpose of this study was to determine whether microglia and short-chain fatty acids were involved in cognitive dysfunction in aged rats. Methods: Male wild-type Wistar rats aged 11–12 months were randomly divided into control group (Ctrl: Veh group), propionic acid group (Ctrl: PA group), exploratory laparotomy group (LP: Veh group) and propionic acid + exploratory laparotomy group (LP: PA group) according to whether exploratory laparotomy (LP) or PA pretreatment for 21 days was performed. The motor ability of the rats was evaluated by open field test on postoperative day 3 (POD3), and then the cognitive function was evaluated by Y-maze test and fear conditioning test. The expression of IL-1β, IL-6, RORγt and IL-17A mRNA in hippocampus was detected by RT-qPCR, the expression of IL-17A and IL-17RA in hippocampus was detected by Western blot, and the activation of microglia was detected by immunofluorescence. Results: The PND rat model was successfully established by laparotomy. Compared with Ctrl: Veh group, the body weight of LP: Veh group decreased, the percentage of spontaneous alternations in Y maze decreased (P

Abstract We here tested the potential activity and the underlying mechanisms of neuroligin-3 (NLGN3) against ischemia-reperfusion-induced neuronal cell injury. In SH-SY5Y neuronal cells and primary murine cortical neurons, NLGN3 activated Akt-mTOR and Erk signalings, and inhibited oxygen and glucose deprivation (OGD)/re-oxygenation (OGD/R)-induced cytotoxicity. Akt activation was required for NLGN3-induced neuroprotection. Gαi1/3 mediated NLGN3-induced downstream signaling activation. NLGN3-induced Akt-S6K1 activation was largely inhibited by Gαi1/3 silencing or knockout. Significantly, NLGN3-induced neuroprotection against OGD/R was almost abolished by Gαi1/3 silencing or knockout. In vivo, the middle cerebral artery occlusion (MCAO) procedure induced NLGN3 cleavage and secretion, and increased its expression and Akt activation in mouse brain tissues. ADAM10 (A Disintegrin and Metalloproteinase 10) inhibition blocked MCAO-induced NLGN3 cleavage and secretion, exacerbating ischemic brain injury in mice. Neuronal silencing of NLGN3 or Gαi1/3 in mice also inhibited Akt activation and intensified MCAO-induced ischemic brain injury. Conversely, neuronal overexpression of NLGN3 increased Akt activation and alleviated MCAO-induced ischemic brain injury. Together, NLGN3 activates Gαi1/3-Akt signaling to protect neuronal cells from ischemia-reperfusion injury.

Chronic heart failure (CHF) is a common complication and cause of death in dialysis patients. Although several clinical guidelines and expert consensus on heart failure (HF) in the general population have been issued in China and abroad, due to abnormal renal function or even no residual renal function (RRF) in dialysis patients, the high number of chronic complications, as well as the specificity, variability, and limitations of hemodialysis (HD) and peritoneal dialysis (PD) treatments, there are significant differences between dialysis patients and the general population in terms of the treatment and management of HF. The current studies are not relevant to all dialysis-combined HF populations, and there is an urgent need for high-quality studies on managing HF in dialysis patients to guide and standardize treatment. After reviewing the existing guidelines and literature, we focused on the staging and diagnosis of HF, management of risk factors, pharmacotherapy, and dialysis treatment in patients on dialysis. Based on evidence-based medicine and clinical trial data, this report reflects new perspectives and future trends in the diagnosis and treatment of HF in dialysis patients, which will further enhance the clinicians’ understanding of HF in dialysis patients.

Oomycete, particularly Phytophthora species, causes the most devastating crop diseases, such as potato late blight, and threatens the sustainable crop production worldwide. Our previous studies identified Resistance to Phytophthora parasitica 1 (RTP1) as a negative regulator of Arabidopsis resistance to multiple biotrophic pathogens and RTP1 loss-of-function plants displayed rapid cell death and reactive oxygen species (ROS) production during early colonization of P. parasitica. In this study, we aim to decipher the mechanism of RTP1-mediated cell death, and identify a member of vaculoar processing enzymes (VPEs), γVPE, playing a role in rtp1-mediated resistance to P. parasitica and cell death occurrence. Our results showed up-regulation of the expression of γVPE as well as increased VPE/caspase 1-like protease activity in P. parasitica-infected rtp1 mutant plants. Besides, we found that the VPE/caspase 1-like protease activity was required for the cell death occurrence in Arabidopsis plants during the infection of P. parasitica as well as rtp1-mediated resistance to P. parasitica. Further pathogenicity assays on either Arabidopsis γvpe mutant plants or leaves of Nicotiana benthamiana with transient overexpression of γVPE demonstrated γVPE could positively affect plant resistance to P. parasitica. Together, our studies suggest that γVPE might function as an important regulator of plant defense and cell death occurrence in response to P. parasitica infection, and VPE/caspase 1-like protease activity is required for rtp1-mediated resistance to P. parasitica.

IntroductionThere is limited evidence regarding particulate matter (PM)’s short-term effects on pulmonary tuberculosis (PTB) hospital admission. Our study aimed to determine the short-term associations of the exposure to ambient PM with aerodynamic diameters

IntroductionEfficiently recognizing emotions is a critical pursuit in brain–computer interface (BCI), as it has many applications for intelligent healthcare services. In this work, an innovative approach inspired by the genetic code in bioinformatics, which utilizes brain rhythm code features consisting of δ, θ, α, β, or γ, is proposed for electroencephalography (EEG)-based emotion recognition.MethodsThese features are first extracted from the sequencing technique. After evaluating them using four conventional machine learning classifiers, an optimal channel-specific feature that produces the highest accuracy in each emotional case is identified, so emotion recognition through minimal data is realized. By doing so, the complexity of emotion recognition can be significantly reduced, making it more achievable for practical hardware setups.ResultsThe best classification accuracies achieved for the DEAP and MAHNOB datasets range from 83–92%, and for the SEED dataset, it is 78%. The experimental results are impressive, considering the minimal data employed. Further investigation of the optimal features shows that their representative channels are primarily on the frontal region, and associated rhythmic characteristics are typical of multiple kinds. Additionally, individual differences are found, as the optimal feature varies with subjects.DiscussionCompared to previous studies, this work provides insights into designing portable devices, as only one electrode is appropriate to generate satisfactory performances. Consequently, it would advance the understanding of brain rhythms, which offers an innovative solution for classifying EEG signals in diverse BCI applications, including emotion recognition.

Abstract Background Elucidation of the post‐transcriptional modification has led to novel strategies to treat intractable tumors, especially glioblastoma (GBM). The ubiquitin‐proteasome system (UPS) mediates a reversible, stringent and stepwise post‐translational modification which is closely associated with malignant processes of GBM. To this end, developing novel therapeutic approaches to target the UPS may contribute to the treatment of this disease. This study aimed to screen the vital and aberrantly regulated component of the UPS in GBM. Based on the molecular identification, functional characterization, and mechanism investigation, we sought to elaborate a novel therapeutic strategy to target this vital factor to combat GBM. Methods We combined glioma datasets and human patient samples to screen and identify aberrantly regulated E3 ubiquitin ligase. Multidimensional database analysis and molecular and functional experiments in vivo and in vitro were used to evaluate the roles of HECT, UBA and WWE domain‐containing E3 ubiquitin ligase 1 (HUWE1) in GBM. dCas9 synergistic activation mediator system and recombinant adeno‐associated virus (rAAV) were used to endogenously overexpress full‐length HUWE1 in vitro and in glioma orthotopic xenografts. Results Low expression of HUWE1 was closely associated with worse prognosis of GBM patients. The ubiquitination and subsequent degradation of N‐Myc mediated by HUWE1, leading to the inactivation of downstream Delta‐like 1 (DLL1)‐NOTCH1 signaling pathways, inhibited the proliferation, invasion, and migration of GBM cells in vitro and in vivo. A rAAV dual‐vector system for packaging and delivery of dCas9‐VP64 was used to augment endogenous HUWE1 expression in vivo and showed an antitumor activity in glioma orthotopic xenografts. Conclusions The E3 ubiquitin ligase HUWE1 acts through the N‐Myc‐DLL1‐NOTCH1 signaling axis to suppress GBM progression. Antitumor activity of rAAV dual‐vector delivering dCas9‐HUWE1 system uncovers a promising therapeutic strategy for GBM.

Exposure of human to parabens (commonly used preservatives) is inevitable due to their extensively applied in numerous consumer products. Thus, a reliable noninvasive matrix reflecting long-term exposure to parabens is essential for human biomonitoring study. Human nails are potentially a valuable alternative for measuring intergrated exposure to parabens. In this work, we collected 100 paired nail and urine samples from university students in Nanjing, China, and measured simultaneously for six parent parabens and four metabolites. Methylparaben (MeP), ethylparaben (EtP), and propylparaben (PrP) were three predominant paraben analogue in both matrices, with the median concentrations being 12.9, 0.753, and 3.42 ng/mL in urine, and 1540, 154, and 961 ng/g in nail, respectively, while 4-hydroxybenzoic acid (4-HB) and 3,4-dihydroxybenzoic acid (3,4-DHB) were the most abundant metabolites (median values of 143 and 35.9 ng/mL, respectively) in urine. Gender-related analysis suggested that females exposed to more higher parabens than males. Significantly positive correlations were found between levels of MeP, PrP, EtP, and OH-MeP (r = 0.54–0.62, p

AimsDevice related thrombus (DRT) is a known complication of left atrial appendage closure (LAAC). However, the relation between DRT and elevated risk of ischemic events remains controversial. This study is sought to reassessed the incidence of DRT following LAAC and the relation between DRT and elevated risk of ischemic stroke and systemic embolism (SE) with latest clinical trials included.MethodsThe PubMed, Embase, and Cochrane Library databases were systematically searched from their inception until April 2022 for studies that reported the incidence of DRT and compared the incidence of both stroke and SE between DRT patients and non-DRT patients.ResultsIn 59 eligible studies, the incidence of DRT was 366/12,845 (2.8%, ranging from 0 to 11%, I2 = 64%). The incidence of DRT was not statistically different between single-seal device (SS) and dual-seal device (DS) in subgroup analysis [171/6,190 (2.8%) vs. 78/3,023 (3.6%); p = 0.93]. The pooled incidence of stroke (26 studies, 7,827 patients) in patients with and without DRT was 11.5% in DRT patients and 2.9% among non-DRT patients (OR: 5.08; 95% CI = 3.47–7.44). In the sensitivity analysis, DRT was associated with higher rate of stroke (12.1 vs. 3.2%; OR: 4.14; 95% CI = 2.69–6.38) and SE (16.0 vs. 3.8%; OR: 4.48; 95% CI = 3.04–6.62).ConclusionThe incidence of DRT was low and similar between SS and DS devices. DRT was associated with increased rates of ischemic events. The occurrence rate of ischemic events associated DRT was comparable between two occlusion mechanism devices.Systematic review registration[https://www.crd.york.ac.uk/], identifier [CRD42022326179].

Two-dimensional (2D) coordination polymers have attracted great attention for catalysis because of their abundant exposed active sites. Here, we show that bending the local structure of 2D coordination polymers can inverse the electrocatalytic selectivity. A series of ultrathin nanosheets based on isoreticular/isostructural/isomeric 2D Cu(I) triazolate coordination polymers were successfully prepared. By introducing an amino group on the triazolate ligand, the shape of the 2D layer transforms from planar into wavy, which inverses the electrocatalytic selectivity from the HER (selectivity ∼ 80%) to the CO2RR (selectivity ∼ 76%, C2H4 up to 52%). Computational simulations showed that the wavy structure allows the amino groups to form attractive hydrogen-bonding interactions with the key reaction intermediates of the CO2RR for C2H4 and steric hindrance with the key reaction intermediates of the HER, giving lower and higher reaction energy barriers, respectively. [ABSTRACT FROM AUTHOR]

Cations and anions are indispensable resources for the development of nature and modern industry and agriculture, and exploring more efficient technology to monitor them is urgently needed. A multifunctional fluorescent probe based on 1,8-naphthalimide, N-(2-thiophenhydrazide)acetyl-4-morpholine-1,8-naphthalimide (TMN), was successfully designed and synthesized for the detection of Co2+, F−, and CN−, with N-carboxymethyl-4-morpholine-1,8-naphthalimide and thiophene-2-carbohydrazide as starting materials. TMN displayed superior stability in MeCN with an “on–off” mode towards Co2+, F−, and CN− by the naked eye. The linear response ranges of TMN were 0–3 and 4–19 μM with a detection limit of 0.21 μM for detecting Co2+, 0–5 and 5–22 μM with a detection limit of 0.36 μM for F−, and 0–10 and 10–25 μM with a detection limit of 0.49 μM for CN−. TMN could also recognize Co2+, F−, and CN− in real samples. Finally, the possible sensing mechanisms of TMN for detecting Co2+, F−, and CN− were deeply investigated. These results implied that TMN could be a potential chemosensor for monitoring metal cations and anions sensitively and selectively and could be used in real sample detection.

Peripheral blood mononuclear cells (PBMCs) of a 38-year-old healthy female were isolated and reprogrammed into the induced pluripotent stem cells (iPSCs). The established iPSC line expressed various pluripotency stem cell markers and potential of differentiating into three germ layers, meanwhile maintained normal karyotype.

Peripheral blood mononuclear cells derived from a 35-year-old healthy male were reprogrammed into induced pluripotent stem cells (iPSCs). The iPSCs maintained a normal karyotype, expressed various pluripotency stem cell markers, and showed potential of differentiating into three germ layers. This iPSCs could be differentiated into multiple cell subtypes for drug discovery and investigation of mechanisms.