A single-cell chromatin accessibility dataset of human primed and naïve pluripotent stem cell-derived teratoma.

Teratoma, due to its remarkable ability to differentiate into multiple cell lineages, is a valuable model for studying human embryonic development. The similarity of the gene expression and chromatin accessibility patterns in these cells to those observed in vivo further underscores its potential as a research tool. Notably, teratomas derived from human naïve (pre-implantation epiblast-like) pluripotent stem cells (PSCs) have larger embryonic cell diversity and contain extraembryonic lineages, making them more suitable to study developmental processes. However, the cell type-specific epigenetic profiles of naïve PSC teratomas have not been yet characterized. Using single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), we analyzed 66,384 cell profiles from five teratomas derived from human naïve PSCs and their post-implantation epiblast-like (primed) counterparts. We observed 17 distinct cell types from both embryonic and extraembryonic lineages, resembling the corresponding cell types in human fetal tissues. Additionally, we identified key transcription factors specific to different cell types. Our dataset provides a resource for investigating gene regulatory programs in a relevant model of human embryonic development.

Slow rupture in a fluid-rich fault zone initiated the 2024 Mw 7.5 Noto earthquake.

The 2024 moment magnitude (Mw) 7.5 Noto Peninsula (Japan) earthquake caused devastation to communities and was generated by a complex rupture process. Using space geodetic and seismic observations, we show that the event deformed the peninsula with a peak uplift reaching 5 m at the west coast. Shallow slip exceeded 10 m on an offshore fault. Peak stress drop was greater than 10 MPa. This devastating event began with a slow rupture propagation lasting 15-20 s near its hypocenter, where seismic swarms had surged since 2020 due to lower-crust fluid supply. The slow start was accompanied by intense high-frequency seismic radiation. These observations suggest a distinct coseismic slip mode reflecting high heterogeneity in fault properties within a fluid-rich fault zone.

BMSCs promote alveolar epithelial cell autophagy to reduce pulmonary fibrosis by inhibiting core fucosylation modifications.

BACKGROUND: Idiopathic pulmonary fibrosis is a chronic progressive interstitial lung disease characterized by alveolar epithelial cell (AEC) injury and fibroblast activation. Inadequate autophagy in AECs may result from the activation of several signaling pathways following AEC injury, with glycoproteins serving as key receptor proteins. The core fucosylation (CF) modification in glycoproteins is crucial. Mesenchymal stem cells derived from bone marrow (BMSCs) have the ability to regenerate damaged tissue and treat pulmonary fibrosis (PF). This study aimed to elucidate the relationship and mechanism of interaction between BMSCs, CF modification, and autophagy in PF. METHODS: C57BL/6 male mice, alveolar epithelial cell-specific FUT8 conditional knockout (CKO) mice, and MLE12 cells were administered bleomycin (BLM), FUT8 siRNA, and mouse BMSCs, respectively. Experimental techniques including tissue staining, western blotting, immunofluorescence, autophagic flux detection, and flow cytometry were utilized in this study. RESULTS: First, we found that autophagy was inhibited while FUT8 expression was elevated in PF mice and BLM-induced AEC injury models. Subsequently, CKO mice and MLE12 cells transfected with FUT8 siRNA were employed to demonstrate that inhibition of CF modification induces autophagy in AECs and mitigates PF. Finally, mouse BMSCs were utilized to demonstrate that they alleviate the detrimental autophagy of AECs by inhibiting CF modification and decreasing PF. CONCLUSIONS: Suppression of CF modification enhanced the suppression of AEC autophagy and reduced PF in mice. Additionally, through the prevention of CF modification, BMSCs can assist AECs deficient in autophagy and partially alleviate PF.

Posterior thoracic antedisplacement and fusion surgery for a special type of ossification of the posterior longitudinal ligament in the thoracic spine: indications and preliminary clinical results of 2-year follow-up.

OBJECTIVES: To describe a novel technique, posterior thoracic antedisplacement and fusion (PTAF), for a special type of ossification of the posterior longitudinal ligament in the thoracic spine (T-OPLL), and to evaluate its safety and efficacy. METHODS: From July to December 2020, five consecutive patients with beak-type T-OPLL located at the thoracic vertebral body (VB) level underwent PTAF surgery. Their demographic data, radiological parameters, perioperative complications, and surgery-related findings were recorded and analyzed. The surgical outcomes were assessed using a modified Japanese Orthopedic Association (mJOA) scale, and the recovery rate (RR) was calculated using the Hirabayashi's method. RESULTS: All patients were followed up for at least two years. The mean thickness of OPLL was 9.4 ± 1.0 mm, and the OPLL spinal canal occupying ratio was 67.7% ± 8.5%. Postoperatively, the mean antedisplacement distance of OPLL was 8.1 ± 1.8 mm, and the average shortened distance of the spinal column was 6.0 ± 1.13 mm. The mean operation time and blood loss were 158.2 ± 26.3 min and 460 ± 89.4 mL, respectively. Perioperative complications were cerebrospinal fluid leakage and instrument failure, 2 cases each. The mean mJOA score was increased from 3.6 ± 2.9 before surgery to 9.4 ± 3.0 at the last follow-up, and the average RR was 84.2 ± 30.5%. CONCLUSION: The preliminary clinical outcomes indicate that PTAF is a safe and effective method for the treatment of beak-type T-OPLL, which has its apex located at the VB level and has a high spinal canal occupation ratio.

Association between strenuous sports or other exercises and lung cancer risk: a mendelian randomization study.

Background: Studying the relationship between strenuous sports or other exercises (SSOE) and lung cancer risk remains underexplored. Traditional observational studies face challenges like confounders and inverse causation. However, Mendelian randomization (MR) provides a promising approach in epidemiology and genetics, using genetic variants as instrumental variables to investigate causal relationships. By leveraging MR, we have scrutinized the causal link between SSOE and lung cancer development. Methods: Twelve single-nucleotide polymorphisms (SNPs) associated with SSOE, as identified in previously published genome-wide association studies, were utilized as instrumental variables in our investigation. Summary genetic data at the individual level were obtained from relevant studies and cancer consortia. The study encompassed a total of 11,348 cases and 15,861 controls. The statistical technique of inverse variance-weighting (IVW), commonly employed in meta-analyses and MR studies, was employed to assess the causal relationship between SSOE and lung cancer risk. Results: The MR risk analysis indicated a causal relationship between SSOE and the incidence of lung cancer, with evidence of a reduced risk for overall lung cancer [odds ratio (OR) =0.129; 95% confidence interval (CI): 0.021-0.779; P=0.03], lung adenocarcinoma (OR =0.161; 95% CI: 0.012-2.102; P=0.16) and squamous cell lung cancer (OR =0.045; 95% CI: 0.003-0.677; P=0.03). The combined OR for lung cancer from SSOE (controlling for waist circumference and smoking status) was 0.054 (95% CI: 0.010-0.302, P<0.001). Conclusions: Our MR analysis findings indicate a potential correlation between SSOE and a protective effect against lung cancer development. Further investigation is imperative to uncover the precise mechanistic link between them.

Corrigendum: Material basis and molecular mechanisms of Chaihuang Qingyi Huoxue Granule in the treatment of acute pancreatitis based on network pharmacology and molecular docking-based strategy.

[This corrects the article DOI: 10.3389/fimmu.2024.1353695.].

Special stent for draining the abdominal abscess respectively from colon and duodenum: A case report.

BACKGROUND: Postoperative abdominal infections are an important and heterogeneous health challenge. Many samll abdominal abscesses are resolved with antibiotics, but larger or symptomatic abscesses may require procedural management. CASE SUMMARY: A 65-year-old male patient who suffered operation for the left hepatocellular carcinoma eight months ago, came to our hospital with recurrent abdominal pain, vomit, and fever for one month. Abdominal computed tomography showed that a big low-density dumbbell-shaped mass among the liver and intestine. Colonoscopy showed a submucosal mass with a fistula at colon of liver region. Gastroscopy showed a big rupture on the submucosal mass at the descending duodenum and a fistula at the duodenal bulb. Under colonoscopy, the brown liquid and pus were drained from the mass with "special stent device". Under gastroscopy, we closed the rupture of the mass with a loop and six clips for purse stitching at the descending duodenum, and the same method as colonoscopy was used to drain the brown liquid and pus from the mass. The symptom of abdominal pain, vomit and fever were relieved after the treatment. CONCLUSION: The special stent device could be effectively for draining the abdominal abscess respectively from colon and duodenum.

[Application of ultrasonic irrigation combined with chlorhexidine in root canal treatment of pulpitis].

PURPOSE: To explore the clinical effect of ultrasonic irrigation combined with chlorhexidine in root canal treatment of pulpitis. METHODS: A total of 120 patients with pulpitis treated with root canal therapy were randomly divided into a study group (n=60, 72 affected teeth) and a control group (n=60, 70 affected teeth). During root canal preparation, the study group was treated with chlorhexidine combined with ultrasonic irrigation, while the control group was treated with chlorhexidine conventional irrigation. The bacterial count and endotoxin content in the root canal before and after root canal preparation were compared between the two groups, as well as the endodontic inter-appointment pain (EIAP), lateral branch root canal filling rate, and degree of tooth pain after root canal treatment. The success rate of treatment was statistically analyzed after one-year follow-up. Statistical analysis was performed with SPSS 19.0 software package. RESULTS: After root canal preparation, the number of colonies in experimental group and control group was significantly decreased compared with that before root canal preparation(P＜0.05), and the number of colonies in experimental group was significantly lower than that in control group(P＜0.05). After root canal preparation, endotoxin levels in experimental group and control group were significantly lower than those before root canal preparation(P＜0.05), and the level in experimental group was significantly lower than that in control group(P＜0.05). The lateral branch root canal filling rate in the study group and the control group was 29.17% and 11.43%, respectively, with significant difference between the groups(P＜0.05). The incidence of EIAP was 4.17% and 14.29%, respectively, with significant difference between the two groups(P＜0.05). At 48 hours after surgery, the visual analogue score (VAS) of the study group and the control group was (2.74±0.61) and (3.29±0.68), respectively, which were significantly lower than at before surgery(P＜0.05). There was a significant difference in VAS score between the two groups 48 hours after surgery(P＜0.05). One week after surgery, the VAS score in the study group and the control group was (1.52±0.34) and (1.81±0.42), respectively, significantly lower than that before and 48 hours after surgery(P＜0.05). There was a significant difference in VAS score between the two groups at one week after surgery (P＜0.05). The successful rate of treatment in the control group was 84.62%, and 95.71% in the study group, with a significant difference between the two groups(P＜0.05). CONCLUSIONS: The application of ultrasonic irrigation combined with chlorhexidine in the treatment of pulpitis root canals can help reduce the level of bacteria and endotoxin after root canal preparation, alleviate the degree of postoperative tooth pain, and improve the filling rate of lateral branch root canals, with superior curative effects.

Modular access to diarylmethyl sulfonamides via visible light-promoted cross-coupling reactions.

We report a novel and efficient method for the preparation of diarylmethyl sulfonamide derivatives through visible-light-induced sulfamoylation of para-quinone methides with sulfamoyl chlorides under mild, metal-free conditions. This protocol demonstrates excellent tolerance toward a wide range of functional groups, affording the corresponding products in moderate to high yields. Preliminary mechanism studies revealed that the excited photocatalyst rhodamine 6G* was mainly quenched by para-quinone methides and the generated diarylmethyl radical intermediates then underwent radical-radical cross-coupling with sulfamoyl radicals to yield the diarylmethyl sulfonamides.

Intratumoral high endothelial venules in solid tumors: a pooled study.

Objective: We performed this pooled analysis for the first time to comprehensively explore the prognostic value of tumor-associated high endothelial venules (TA-HEVs) and determine their relationships with clinicopathological features in solid tumors. Methods: Four online databases, including PubMed, Web of Science, Embase, and Cochrane Library, were comprehensively searched to identify studies assessing the effect of TA-HEVs on prognosis or clinicopathological features. Hazard ratios (HRs) with 95% confidence intervals (CIs) were applied to evaluate survival outcomes, including overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and cancer-specific survival (CSS). The association between TA-HEV status and clinicopathological characteristics was assessed by odds ratios (ORs) combined with 95% CIs. Subgroup analysis was conducted to explore sources of heterogeneity. The sensitivity analysis was performed to evaluate the stability of our findings. Meanwhile, Funnel plots were employed to visually evaluate potential publication bias, and both Begg's and Egger's tests were adopted to quantitatively determine publication bias. Results: A total of 13 retrospective cohort studies, involving 1,933 patients were finally included in this meta-analysis. Effect-size pooling analysis showed that the positivity of TA-HEVs was related to improved OS (pooled HR: 0.75, 95% CI: 0.62-0.93, P<0.01), and DFS (pooled HR = 0.54, 95% CI = 0.41-0.72, P< 0.01). However, TA-HEV positivity in solid tumors was not linked to PFS (pooled HR = 0.75, 95% CI 0.34-1.64, P = 0.47) or CSS (pooled HR: 0.58, 95% CI: 0.04-7.58, P= 0.68). Further subgroup analysis demonstrated that ethnicity and source of HR were the main factors contributing to heterogeneity. Moreover, TA-HEVs were inversely associated with lymph node metastasis and distant metastasis, but were positively related to worse tumor differentiation. However, TA-HEVs were not significantly correlated with sex, LVI, clinical stage, and depth of invasion. Sensitivity analysis suggested that the pooled results were stable and reliable, with no significant publication bias in all included articles. Conclusions: This is the first comprehensive analysis of the prognostic value of TA-HEVs in solid tumors using existing literature. Overall, our study demonstrated a significant correlation between TA-HEVs and prognosis as well as clinicopathological features. TA-HEVs may serve as novel immune-related biomarkers for clinical assessments and prognosis prediction in solid tumors. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php, identifier CRD42023394998.

Targeting MS4A4A: A novel pathway to improve immunotherapy responses in glioblastoma.

INTRODUCTION: Glioblastoma (GBM) remains a challenging brain tumor to treat, with limited response to PD-1 immunotherapy due to tumor-associated macrophages (TAMs), specifically the M2 phenotype. This study explores the potential of MS4A4A (membrane spanning four domains, subfamily A, member 4A) inhibition in driving M2 macrophage polarization toward the M1 phenotype via the ferroptosis pathway to enhance the effectiveness of immunotherapy in GBM. METHODS: Single-cell RNA sequencing and spatial transcriptomic analyses were employed to characterize M2 macrophages and MS4A4A expression in GBM. In vitro studies utilizing TAM cultures, flow cytometry, and western blot validations were conducted to assess the impact of MS4A4A on the tumor immune microenvironment and M2 macrophage polarization. In vivo models, including subcutaneous and orthotopic transplantation in mice, were utilized to evaluate the effects of MS4A4A knockout and combined immune checkpoint blockade (ICB) therapy on tumor growth and response to PD-1 immunotherapy. RESULTS: Distinct subsets of GBM-associated macrophages were identified, with spatial distribution in tumor tissue elucidated. In vivo experiments demonstrated that inhibiting MS4A4A and combining ICB therapy effectively inhibited tumor growth, reshaped the tumor immune microenvironment by reducing M2 TAM infiltration and enhancing CD8+ T-cell infiltration, ultimately leading to complete tumor eradication. CONCLUSION: MS4A4A inhibition shows promise in converting M2 macrophages to M1 phenotype via ferroptosis, decreasing M2-TAM infiltration, and enhancing GBM response to PD-1 immunotherapy. These findings offer a novel approach to developing more effective immunotherapeutic strategies for GBM.

The Identification of Kabatiella zeae as a Causal Agent of Northern Anthracnose of Sorghum in China and Estimation of Host Resistance.

Sorghum northern anthracnose is a leaf disease affecting sorghum, which results in plant death and substantial yield loss. This study aimed to effectively understand the disease, clarify its biological characteristics, and evaluate the resistance of germplasm resources. A field sample was collected to isolate and purify the pathogen. The pathogen, identified as Kabatiella zeae Narita et Hiratsuka using both morphological and molecular techniques, was further confirmed as the causative agent of northern anthracnose of sorghum following Robert Koch's principles. The results revealed the optimal culture temperature to be 25 °C, preferred dark culture conditions, and the best growth on potato glucose agar medium with sucrose and L-leucine as the optimal carbon and nitrogen sources, respectively. A total of 138 sorghum germplasm resources were inoculated and evaluated using the isolated pathogen, with 20 lines (14.49%) exhibiting high resistance, 18 lines (13.04%) showing disease resistance, 27 lines (19.57%) demonstrating medium resistance, 37 lines (26.81%) being susceptible, and 36 lines (26.09%) classified as highly susceptible. The indoor fungicide screening was conducted through pathogen medium application, and enilconazole, pyraclostrobin, methylthiophanate, and flusilazole were screened for the best fungicide inhibition with a 100% inhibition rate compared with the control. This study provides reference for field pharmaceutical control in sorghum production.

Multi-omics integration identifies ferroptosis involved in black phosphorus quantum dots-induced renal injury.

Black phosphorus quantum dots (BPQDs) have recently emerged as a highly promising contender in biomedical applications ranging from drug delivery systems to cancer therapy modalities. Nevertheless, the potential toxicity and its effects on human health need to be thoroughly investigated. In this study, we utilized multi-omics integrated approaches to explore the complex mechanisms of BPQDs-induced kidney injury. First, histological examination showed severe kidney injury in male mice after subacute exposure to 1 mg/kg BPQDs for 28 days. Subsequently, transcriptomic and metabolomic analyses of kidney tissues exposed to BPQDs identified differentially expressed genes and metabolites associated with ferroptosis, an emerging facet of regulated cell death. Our findings highlight the utility of the multi-omics integrated approach in predicting and elucidating potential toxicological outcomes of nanomaterials. Furthermore, our study provides a comprehensive understanding of the mechanisms driving BPQDs-induced kidney injury, underscoring the importance of recognizing ferroptosis as a potential toxic mechanism associated with BPQDs.

Triazine-structured covalent organic framework nanosheets with inherent hydrophilicity for the highly efficient and selective enrichment of glycosylated peptides.

Protein glycosylation plays a crucial role in various biological processes and is related to various diseases. Highly specific enrichment of glycopeptides before mass spectrometry detection is crucial for comprehensive glycoproteomic analysis. However, it still remains a great challenge due to the absence of affinity materials with excellent enrichment efficiency. In this work, a triazine structure linked by a -NH- bond of two-dimensional (2-D) covalent organic framework (COF) nanosheets was synthesized as an affinity adsorbent for the selective capture of glycopeptides. In particular, by introducing hydrophilic monomers via a bottom-up approach, the 2-D COF (denoted as NENP-1) nanosheets were provided with abundant amino groups and inherent hydrophilicity. Owing to the specific surface area and excessive accessible sites for hydrophilicity, the resulting NENP-1 nanosheets exhibited an outstanding glycopeptide enrichment efficiency from standard samples with a superior detection sensitivity (1 × 10-10 M), good enrichment selectivity (1 : 800, HRP tryptic digest to BSA protein), excellent binding capacity (100 mg g-1), great reusability, and recovery (60.2%). Furthermore, using the NENP-1 nanosheet adsorbent, twenty-four endogenous glycopeptides in the serum of patients with gastric cancer were successfully identified by LC-MS/MS technology, which illustrates a promising prospective of hydrophilic COF nanosheets in glycoproteomics research.

A NIR-II absorbing conjugated polymer based on tetra-fused isoindigo with ultrahigh photothermal conversion efficiency for cancer therapy.

A conjugated polymer, P4TTD-DPP, based on tetra-fused isoindigo-alt-diketopyrrolopyrrole, has been synthesized as a photothermal therapeutic nanotransducer within the near-infrared-II (NIR-II) window. P4TTD-DPP exhibits a notable mass extinction coefficient of 62.8 L g-1 cm-1 at 1064 nm. Additionally, P4TTD-DPP nanoparticles demonstrate remarkable photothermal conversion efficiency of 91.5% at 1064 nm and exhibit excellent anticancer efficacy under photothermal conditions.

Raspberry Ketone Attenuates Hepatic Fibrogenesis and Inflammation via Regulating the Crosstalk of FXR and PGC-1α Signaling.

Hepatic fibrosis is a compensatory response to chronic liver injury and inflammation, and dietary intervention is recommended as one of the fundamental prevention strategies. Raspberry ketone (RK) is an aromatic compound first isolated from raspberry and widely used to prepare food flavors. The current study investigated the hepatoprotection and potential mechanism of RK against hepatic fibrosis. In vitro, hepatic stellate cell (HSC) activation was stimulated with TGF-ß and cultured with RK, farnesoid X receptor (FXR), or peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) agonist or inhibitor, respectively. In vivo, C57BL/6 mice were injected intraperitoneally with thioacetamide (TAA) at 100/200 mg/kg from the first to the fifth week. Mice were intragastrically administrated with RK or Cur once a day from the second to the fifth week. In activated HSCs, RK inhibited extracellular matrix (ECM) accumulation, inflammation, and epithelial-mesenchymal transition (EMT) process. RK both activated FXR/PGC-1α and regulated their crosstalk, which were verified by their inhibitors and agonists. Deficiency of FXR or PGC-1α also attenuated the effect of RK on the reverse of activated HSCs. RK also decreased serum ALT/AST levels, liver histopathological change, ECM accumulation, inflammation, and EMT in mice caused by TAA. Double activation of FXR/PGC-1α might be the key targets for RK against hepatic fibrosis. Above all, these discoveries supported the potential of RK as a novel candidate for the dietary intervention of hepatic fibrosis.

A novel prognostic signature related to programmed cell death in osteosarcoma.

Background: Osteosarcoma primarily affects children and adolescents, with current clinical treatments often resulting in poor prognosis. There has been growing evidence linking programmed cell death (PCD) to the occurrence and progression of tumors. This study aims to enhance the accuracy of OS prognosis assessment by identifying PCD-related prognostic risk genes, constructing a PCD-based OS prognostic risk model, and characterizing the function of genes within this model. Method: We retrieved osteosarcoma patient samples from TARGET and GEO databases, and manually curated literature to summarize 15 forms of programmed cell death. We collated 1621 PCD genes from literature sources as well as databases such as KEGG and GSEA. To construct our model, we integrated ten machine learning methods including Enet, Ridge, RSF, CoxBoost, plsRcox, survivalSVM, Lasso, SuperPC, StepCox, and GBM. The optimal model was chosen based on the average C-index, and named Osteosarcoma Programmed Cell Death Score (OS-PCDS). To validate the predictive performance of our model across different datasets, we employed three independent GEO validation sets. Moreover, we assessed mRNA and protein expression levels of the genes included in our model, and investigated their impact on proliferation, migration, and apoptosis of osteosarcoma cells by gene knockdown experiments. Result: In our extensive analysis, we identified 30 prognostic risk genes associated with programmed cell death (PCD) in osteosarcoma (OS). To assess the predictive power of these genes, we computed the C-index for various combinations. The model that employed the random survival forest (RSF) algorithm demonstrated superior predictive performance, significantly outperforming traditional approaches. This optimal model included five key genes: MTM1, MLH1, CLTCL1, EDIL3, and SQLE. To validate the relevance of these genes, we analyzed their mRNA and protein expression levels, revealing significant disparities between osteosarcoma cells and normal tissue cells. Specifically, the expression levels of these genes were markedly altered in OS cells, suggesting their critical role in tumor progression. Further functional validation was performed through gene knockdown experiments in U2OS cells. Knockdown of three of these genes-CLTCL1, EDIL3, and SQLE-resulted in substantial changes in proliferation rate, migration capacity, and apoptosis rate of osteosarcoma cells. These findings underscore the pivotal roles of these genes in the pathophysiology of osteosarcoma and highlight their potential as therapeutic targets. Conclusion: The five genes constituting the OS-PCDS model-CLTCL1, MTM1, MLH1, EDIL3, and SQLE-were found to significantly impact the proliferation, migration, and apoptosis of osteosarcoma cells, highlighting their potential as key prognostic markers and therapeutic targets. OS-PCDS enables accurate evaluation of the prognosis in patients with osteosarcoma.

Sensitive and accurate monitoring of urinary albumin and point-of-care testing using a fluorescent probe with anti-interference capacity against exogenous drugs.

Fluorescent probes have been reported for monitoring urinary albumin (u-ALB) to enable early diagnosis of kidney diseases and facilitate regular point-of-care testing (POCT) for chronic kidney disease (CKD) patients. However, the albumin can bind hydrophobic drugs through host-guest interactions, which may result in decreased accuracy of probes at regular drug sites and hamper POCT of albuminuria since CKD patients often need to take medications routinely. Herein, we reported a novel fluorescent probe (NC-2) by molecular engineering of a reported AIEgen (NC-1). The introduction of a non-conjugated ring moiety to the molecular rotor granted the NC-2 enhanced sensitivity with a limit of detection in urine of 8.7 mg/L, which is below l the threshold of microalbuminuria (30 mg/L). Moreover, the NC-2 was found to preferentially bind to the FA1 site of ALB, conferring it with excellent anti-interference capacities against exogenous drug molecules and metabolites. Simulation experiments using lab-spiked urine samples containing common drugs taken by CKD patients demonstrated that the probe could provide satisfied detecting accuracy (80-90 %). Furthermore, a paper-based device was constructed and achieved on-site detection of u-ALB in qualitative and semi-quantitative manners. Findings in this work were of great significance to the development of fluorescent probes for accurate detection of ALB in complex urine samples and the further achievement of fluorescence-based POCT for CKD.

Dorsoventral heterogeneity of synaptic connectivity in hippocampal CA3 pyramidal neurons.

The hippocampal CA3 region plays an important role in learning and memory. CA3 pyramidal neurons (PNs) receive two prominent excitatory inputs - mossy fibers (MFs) from dentate gyrus (DG) and recurrent collaterals (RCs) from CA3 PNs - that play opposing roles in pattern separation and pattern completion, respectively. Although the dorsoventral heterogeneity of the hippocampal anatomy, physiology, and behavior has been well established, nothing is known about the dorsoventral heterogeneity of synaptic connectivity in CA3 PNs. In this study, we performed Timm's sulfide silver staining, dendritic and spine morphological analyses, and ex vivo electrophysiology in mice of both sexes to investigate the heterogeneity of MF and RC pathways along the CA3 dorsoventral axis. Our morphological analyses demonstrate that ventral CA3 (vCA3) PNs possess greater dendritic lengths and more complex dendritic arborization, compared to dorsal CA3 (dCA3) PNs. Moreover, using ChannelRhodopsin2 (ChR2)-assisted patch-clamp recording, we find that the ratio of the RC-to-MF excitatory drive onto CA3 PNs increases substantially from dCA3 to vCA3, with vCA3 PNs receiving significantly weaker MFs, but stronger RCs, excitation than dCA3 PNs. Given the distinct roles of MF versus RC inputs in pattern separation versus completion, our findings of the significant dorsoventral variations of MF and RC excitation in CA3 PNs may have important functional implications for the contribution of CA3 circuit to the dorsoventral difference in hippocampal function.Significance Statement The hippocampal CA3 region is essential for memory formation. CA3 pyramidal neurons receive recurrent collateral (RC) from CA3 and mossy fiber (MF) from dentate gyrus (DG), which have opposite functions in pattern completion (memory generalization) and separation (discrimination), respectively. Although hippocampal dorsoventral heterogeneity is well established, dorsoventral heterogeneity of CA3 connectivity is unknow. Here, we demonstrate that the ratio of RC-to-MF excitation increases substantially from dCA3 to vCA3, with vCA3 receiving significantly weaker MF, but stronger RC, excitation than dCA3. Thus, our study reveals a novel CA3-based synaptic mechanism that may offer the computational advantage for the ventral hippocampus to be more strongly involved in behaviors that require less precision but more generalization than the dorsal hippocampus.