Single-Cell Spatial Transcriptomics Unveils Platelet-Fueled Cycling Macrophages for Kidney Fibrosis.

With the increasing incidence of kidney diseases, there is an urgent need to develop therapeutic strategies to combat post-injury fibrosis. Immune cells, including platelets, play a pivotal role in this repair process, primarily through their released cytokines. However, the specific role of platelets in kidney injury and subsequent repair remains underexplored. Here, the detrimental role of platelets in renal recovery following ischemia/reperfusion injury and its contribution to acute kidney injury  to chronic kidney disease transition is aimed to investigated. In this study, it is shown that depleting platelets accelerates injury resolution and significantly reduces fibrosis. Employing advanced single-cell and spatial transcriptomic techniques, macrophages as the primary mediators modulated by platelet signals is identified. A novel subset of macrophages, termed "cycling M2", which exhibit an M2 phenotype combined with enhanced proliferative activity is uncovered. This subset emerges in the injured kidney during the resolution phase and is modulated by platelet-derived thrombospondin 1 (THBS1) signaling, acquiring profibrotic characteristics. Conversely, targeted inhibition of THBS1 markedly downregulates the cycling M2 macrophage, thereby mitigating fibrotic progression. Overall, this findings highlight the adverse role of platelet THBS1-boosted cycling M2 macrophages in renal injury repair and suggest platelet THBS1 as a promising therapeutic target for alleviating inflammation and kidney fibrosis.

Application of artificial intelligence in gastrointestinal endoscopy.

Endoscopy is an important method for diagnosing gastrointestinal (GI) diseases. In this study, we provide an overview of the advances in artificial intelligence (AI) technology in the field of GI endoscopy over recent years, including esophagus, stomach, large intestine, and capsule endoscopy (small intestine). AI-assisted endoscopy shows high accuracy, sensitivity, and specificity in the detection and diagnosis of GI diseases at all levels. Hence, AI will make a breakthrough in the field of GI endoscopy in the near future. However, AI technology currently has some limitations and is still in the preclinical stages.

Case Report: Transcatheter treatment of aortic coarctation in a 58-year-old patient with LACHT syndrome and left lung agenesis.

LACHT (Lung Agenesis, Congenital Heart, and Thumb anomalies) syndrome is an extremely rare congenital anomaly and presents significant challenges in adults due to its poor survival rates. Herein, we report a case of late diagnosis and successful transcatheter treatment of aortic coarctation in a 58-year-old male patient with LACHT syndrome, medically resistant arterial hypertension, and left lung agenesis. Baseline CT angiography showed isthmic aortic coarctation and left lung agenesis, with compensatory right pulmonary artery and vein thickenings. The patient underwent balloon dilation and subsequent implantation of a covered NuMED 45 mm 8-ZIG CP stent with satisfactory outcomes. The pressure gradient decreased from 43 to 23 mmHg. The arterial pressures normalized during the follow-up with fewer medications. Genetic testing identified a heterozygous mutation (c.6583C > T) in the FBN2, supporting the diagnosis of variant Marfan syndrome.

Emerging Pharmacotherapeutic Strategies to Overcome Undruggable Proteins in Cancer.

Targeted therapies in cancer treatment can improve in vivo efficacy and reduce adverse effects by altering the tissue exposure of specific biomolecules. However, there are still large number of target proteins in cancer are still undruggable, owing to the following factors including (1) lack of ligand-binding pockets, (2) function based on protein-protein interactions (PPIs), (3) the highly specific conserved active sites among protein family members, and (4) the variability of tertiary docking structures. The current status of undruggable targets proteins such as KRAS, TP53, C-MYC, PTP, are carefully introduced in this review. Some novel techniques and drug designing strategies have been applicated for overcoming these undruggable proteins, and the most classic and well-known technology is proteolysis targeting chimeras (PROTACs). In this review, the novel drug development strategies including targeting protein degradation, targeting PPI, targeting intrinsically disordered regions, as well as targeting protein-DNA binding are described, and we also discuss the potential of these strategies for overcoming the undruggable targets. Besides, intelligence-assisted technologies like Alpha-Fold help us a lot to predict the protein structure, which is beneficial for drug development. The discovery of new targets and the development of drugs targeting them, especially those undruggable targets, remain a huge challenge. New drug development strategies, better extraction processes that do not disrupt protein-protein interactions, and more precise artificial intelligence technologies may provide significant assistance in overcoming these undruggable targets.

Calculated inflammatory markers derived from complete blood count results, along with routine laboratory and clinical data, predict treatment failure of acute peritonitis in chronic peritoneal dialysis patients.

BACKGROUND & AIMS: Complete blood count (CBC)-derived inflammatory markers are predictive biomarkers for the prognosis of many diseases. However, there was no study on patients with peritoneal dialysis-associated peritonitis (PDAP). We aimed to investigate the value of these markers in predicting treatment failure of acute peritonitis in chronic PD patients. METHODS: The records of 138 peritonitis episodes were reviewed and divided into treatment success or failure groups in a single center for 10 years. CBC-derived markers and other routine data were recorded before peritonitis treatment was initiated. Univariate and multivariate regression analyses and the receiver operating characteristic (ROC) curve about the predictors of treatment outcomes were performed. RESULTS: Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and derived NLR were significantly higher in the failure group. Univariate logistic regression results showed that NLR and PLR were risk factors of treatment outcomes. The backward stepwise multivariate logistic regression results demonstrated that NLR [adjusted odds ratio (aOR), 1.376; 95% confidence intervals (CI), 1.105-1.713; p = .004], PLR (aOR, 1.010; 95%CI, 1.004-1.017; p = .002) were risk factors, but hemoglobin-to-lymphocyte ratio (HLR) (aOR, 0.977; 95%CI, 0.963-0.991; p = .001), and SII (aOR, 0.999; 95%CI, 0.998-1.000; p = .040) were protective factors. A combination of age, PD vintage, Gram-positive peritonitis, staphylococcus aureus, culture-negative, NLR, PLR, HLR, and SII would improve prognostic performance. The area under this ROC curve was 0.85, higher than other factors. CONCLUSIONS: NLR, PLR, HLR, and SII were associated with PDAP outcomes. Age, PD vintage, NLR, and PLR were significant risk factors in PDAP patients.

Effect of national holidays on health outcomes of patients receiving peritoneal dialysis in a single center over a ten-year period.

BACKGROUND: National holidays are associated with high mortality in some diseases, but little is known about patients undergoing peritoneal dialysis (PD). The research aimed to investigate the impact of national holidays on the health outcomes of PD patients. METHODS: Over ten years, all episodes of unplanned hospitalization, death, and peritonitis in PD patients were collected in our center. Seven national holidays in China were chosen, and non-holiday days were selected as the control period. The effect of national holidays was observed by comparing the hospitalization, death, and peritonitis rates between holiday and non-holiday groups. RESULTS: There were 297 events in all holiday periods and 1247 in non-holiday periods. There is no significant difference in hospitalization rate between holiday and non-holiday groups (32.4% ± 6.4% vs. 29.2% ± 3.4%, p = 0.175). So is the death rate [6.3% (4.8-12.3%) vs.5.0% (4.2-8.9%), p = 0.324] and peritonitis rate [0.19 (0.13-0.53) vs. 0.22 (0.18-0.27), p = 0.445] between the two groups. Significant differences were observed in the distribution of peritonitis causes between the two groups (p = 0.017). The rate of secondary to other infections in the holiday group was significantly higher than in the non-holiday group (25.0 vs. 10.3%, p = 0.015). CONCLUSION: Our study suggested no national holiday effect on health outcomes of PD patients based on ten-year data in our center.

A Complete Genome of Nocardia terpenica NC_YFY_NT001 and Pan-Genomic Analysis Based on Different Sources of Nocardia spp. Isolates Reveal Possibly Host-Related Virulence Factors.

Objective: We aimed to identify the possible virulence genes associated with Nocardia NC_YFY_NT001 isolated by ourselves and other Nocardia spp. Methods: The genome of Nocardia terpenica NC_YFY_NT001 was completed by using PacBio and Illumina platforms. A pan-genomic analysis was applied to selected complete Nocardia genomes. Results: Nocardia terpenica NC_YFY_NT001 can cause healthy mice death by tail intravenous injection. The genome of NT001 has one circular chromosome 8,850,000 bp and one circular plasmid 70,000 bp with ~68% GC content. The chromosome and plasmid encode 7914 and 80 proteins, respectively. Furthermore, a pan-genomic analysis showed a total of 45,825 gene clusters, then 304 core, 21,045 shell and 24,476 cloud gene clusters were classified using specific parameters. In addition, we found that catalases were more abundant in human isolates. Furthermore, we also found no significant differences in the MCE proteins between different strains from different sources. The pan-genomic analysis also showed that 67 genes could only be found in humoral isolates. ReX3 and DUF853 domain protein were found in all eight human isolates. The composition of unique genes in humoral isolate genomes indicated that the transcriptional regulators may be important when Nocardia invades the host, which allows them to survive in the new ecological system. Conclusion: In this study, we confirmed that NT001 could cause infected animal death, and identified many possible virulence factors for our future studies. This study also provides new insight for our further study on Nocardia virulence mechanisms.