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Tuberculosis (TB) stands as the second most fatal infectious disease after COVID‐19, the effective treatment of which depends on accurate diagnosis and phenotyping. Metabolomics provides valuable insights into the identification of differential metabolites for disease diagnosis and phenotyping. However, TB diagnosis and phenotyping remain great challenges due to the lack of a satisfactory metabolic approach. Here, a metabolomics‐based diagnostic method for rapid TB detection is reported. Serum metabolic fingerprints are examined via an automated nanoparticle‐enhanced laser desorption/ionization mass spectrometry platform outstanding by its rapid detection speed (measured in seconds), minimal sample consumption (in nanoliters), and cost‐effectiveness (approximately $3). A panel of 14 m z−1 features is identified as biomarkers for TB diagnosis and a panel of 4 m z−1 features for TB phenotyping. Based on the acquired biomarkers, TB metabolic models are constructed through advanced machine learning algorithms. The robust metabolic model yields a 97.8% (95% confidence interval (CI), 0.964‐0.986) area under the curve (AUC) in TB diagnosis and an 85.7% (95% CI, 0.806‐0.891) AUC in phenotyping. In this study, serum metabolic biomarker panels are revealed and develop an accurate metabolic tool with desirable diagnostic performance for TB diagnosis and phenotyping, which may expedite the effective implementation of the end‐TB strategy. [ABSTRACT FROM AUTHOR]

The transcription factor TFEB is a major regulator of lysosomal biogenesis and autophagy. There is growing evidence that posttranslational modifications play a crucial role in regulating TFEB activity. Here, we show that lactate molecules can covalently modify TFEB, leading to its lactylation and stabilization. Mechanically, lactylation at K91 prevents TFEB from interacting with E3 ubiquitin ligase WWP2, thereby inhibiting TFEB ubiquitination and proteasome degradation, resulting in increased TFEB activity and autophagy flux. Using a specific antibody against lactylated K91, enhanced TFEB lactylation was observed in clinical human pancreatic cancer samples. Our results suggest that lactylation is a novel mode of TFEB regulation and that lactylation of TFEB may be associated with high levels of autophagy in rapidly proliferating cells, such as cancer cells., (© 2024 Huang et al.)

Biofilm-associated surgical site infection (BSSI) is a common and grievous postoperative complication lacking effective remedies, mainly due to the poor drug accumulation and penetration in the biofilms featured by dense extracellular polymeric substances (EPSs). Here, it is found that the vascular cell adhesion molecule-1 (VCAM1) is highly overexpressed in the vascular cells of BSSI. It is proposed that the combination of VCAM1-mediated transcytosis and ultrasonic cavitation can consecutively overcome the biological barriers of vascular endothelial cells and EPS for biofilm eradication. To demonstrate the feasibility, a VCAM1-targeted and ultrasound (US)-activated liposome (LPCOTML) loaded with a reactive-oxygen-species (ROS)-responsive lipoid prodrug of oleoyl meropenem, sonosensitizer of lipoid Ce6, and perfluoropentane is developed. LPCOTML can recognize the receptors on vascular cells, and initiate receptor-mediated transcytosis for transendothelial transport into the BSSI periphery. LPCOTML subsequently transforms from nanoparticle into microbubble via liquid-gas phase transition under US irradiation, triggering strong ultrasonic cavitation to blow up the EPS and deeply penetrate the biofilms. The sonosensitizer Ce6 induces ROS production under US irradiation and triggers the release of meropenem to induce potent antibacterial effect in a BSSI model. This study presents an effective strategy to tackle the biological barriers in BSSI via combining receptor-mediated transcytosis and ultrasonic cavitation., (© 2024 Wiley‐VCH GmbH.)

Aims: Performing prophylactic central lymph node dissection for papillary thyroid microcarcinoma (PTMC) patients with clinically negative lymph node metastasis remains controversial - not all patients with PTMC are suitable for active surveillance. Therefore, we aimed to establish a nomogram based on ultrasound features for predicting CLNM in PTMC., Material and Methods: This retrospective study included 636 patients with PTMC, in which the CLNM status was pathologically confirmed. Univariate and multivariate regression analyses were conducted to screen for risk factors associated with CLNM. Then, a CLNM prediction model was established, receiver operating characteristic, calibration, and decision curve analyses were used to assess the model's performance., Results: Five variables, including age, sex, combined CLNM status, tumor size, and capsule invasion, were included in the nomogram. The values of the area under the receiver operating characteristic curve in the training and validation datasets were 0.720 (95% confidence interval [CI], 0.649-0.791) and 0.704 (95% CI, 0.622-0.786), respectively., Conclusions: An ultrasound-based nomogram was successfully established, of which the predictive model shows excellent predictive performance and can be used to evaluate the status of CLNM in PTMC. Thus, patients with high nomogram scores should be considered for prophylactic central neck dissection.

Introduction: Epidermoid cyst in an intra-pancreatic accessory spleen (ECIPAS) is an exceedingly rare pancreatic lesion that is always mistakenly suspected of malignancy preoperatively., Case Summary: A 25-year-old male incidentally found a giant mass in the left upper abdomen neighboring the hilum of the spleen. The patient denied any obvious discomfort. Except for a slightly elevated carbohydrate antigen 19-9 (CA19-9, 43.5 U/ml), no abnormal laboratory test results were found. Contrast-enhanced computed tomography (CT), conventional ultrasound (US), and magnetic resonance imaging (MRI) were performed. The patient received a laparoscopic distal pancreatectomy. The final pathology showed ECIPAS. The postoperative course was uneventful and no signs of recurrence during 2 years of follow-up., Discussion: For an incidental pancreatic cystic lesion (PCL), ECIPAS should be considered in the differential diagnosis. ECIPAS may mimic pancreatic cystadenoma. Imaging follow-up or surgical removal may be useful for the exclusion of malignant risks in ECIPAS., Competing Interests: Conflict of interest: The authors declare that there is no conflict of interest. Authorship: R.Y. and P.H. designed this study. J.L. and F.H. acquired the data. Y.S. wrote the main manuscript text. All authors reviewed the manuscript. The authors confirm no conflict of interests related to this study., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The aim of this study was to evaluate the safety and efficacy of ultrasound-guided radiofrequency ablation (RFA) for the management of papillary thyroid microcarcinoma (PTMC) close to the thyroid capsule., Material and Methods: This was a retrospective study of 202 patients with PTMC who underwent RFA close to the thyroid capsule and 80 patients with PTMC who underwent RFA far from the thyroid capsule between June 2015 and December 2022. The follow-up time after RFA, change in size of tumour, location, thyroid function, the rates of PTMC disappearance, and complications were evaluated., Results: A total of 202 patients with PTMC close to the thyroid capsule and 80 patients with PTMC far from the thyroid capsule successfully treated with RFA were studied. The thyroid function including free triiodothyronine (fT3), free thyroxine (fT4), triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) showed no changes after RFA for one months in both groups. The tumour size was increased at 1, 3, and 6 months after RFA compared with pre-operative RFA in both groups. The tumour size was decreased at 12 and 24 months after RFA compared with pre-operative RFA both in both group. Seventy-nine PTMC close to the thyroid capsule and 30 PTMC far from the thyroid capsule completely disappeared as assessed by ultrasound examination. Eighty-four PTMC patients close to the thyroid capsule and 34 PTMC patients far from the thyroid capsule had minor complications after RFA treatment. The complication rates between the 2 groups were similar., Conclusion: Ultrasound-guided RFA seems to be an effective and safe method for patients with PTMC close to the thyroid capsule.