Erratum: TUG1 promotes the expression of IFITM3 in hepatocellular carcinoma by competitively binding to miR-29a: Erratum.

[This corrects the article DOI: 10.7150/jca.57477.].

Resistance to Thyroid Hormone Beta Due to THRB Mutation in a Patient Misdiagnosed With TSH-Secreting Pituitary Adenoma.

Elevated concentrations of T3 and T4 concomitant with nonsuppressed TSH are found in both TSH-producing tumors and resistance to thyroid hormone beta (RTHß), posing a diagnostic challenge. We demonstrate here a 54-year-old female who presented with palpitations, goiter, and elevated free T4 with nonsuppressed TSH concentrations (TSH 2.2 mIU/L [normal range, NR 0.27-4.2 mIU/L] and FT4 59.08 pmol/L [NR 12.0-22.0 pmol/L]). Because magnetic resonance imaging revealed a pituitary microadenoma (4 mm), she was diagnosed with TSH-secreting pituitary adenoma and underwent transsphenoidal surgery. Pathological reports showed no tumor cells. Subsequent genetic testing revealed a pathogenic variant in the THRB gene resulting in a His435Arg amino acid substitution in the T3 receptor isoform beta 1 (TRß1), suggestive of RTHß. In vitro and ex vivo studies revealed that the His435Arg mutated TRß1 (TRß1-H435R) completely abolishes the T3-induced transcriptional activation, nuclear receptor corepressor 1 release, steroid receptor coactivator 1 recruitment, and T3-induced thyroid hormone target gene expression, confirming the pathogenicity of this variant. The identification of a pituitary microadenoma in a patient with RTHß led to a misdiagnosis of a TSH-producing tumor and unnecessary surgery. Genetic testing proved pivotal for an accurate diagnosis, suggesting earlier consideration in similar clinical scenarios.

Real-Time pH Sensor in Bacterial Microenvironments Using Liquid Crystal Core-Shell Microspheres.

It is well-known that the bacterial microenvironment imposes restrictions on the growth and behavior of bacteria. The localized monitoring of microenvironmental factors is appreciated when consulting bacterial adaptation and behavior in the presence of chemical or mechanical stimuli. Herein, we developed a novel liquid crystal (LC) biosensor in a microsphere configuration for real-time 3D monitoring of the bacteria microenvironment, which was implemented by a microfluidic chip. As a proof of concept, a LC gel (LC-Gel) microsphere biosensor was prepared and employed in the localized pH changes of bacteria by observing the configuration change of LC under polarized optical microscopy. Briefly, the microsphere biosensor was constructed in core-shell configuration, wherein the core contained LCE7 (a nematic LC) doped with 4-pentylbiphenyl-4'-carboxylic acid (PBA), and the shell encapsulated the bacteria. The protonation of carboxyl functional groups of the PBA induced a change in charge density on the surface of LCE7 and the orientation of E7 molecules, resulting in the transitions of the LC nucleus from axial to bipolar. The developed LC-Gel microspheres pH sensor exhibited its dominant performance on localized pH real-time sensing with a resolution of 0.1. An intriguing observation from the prepared pH biosensor was that the diverse bacteria impelled distinct acidifying or alkalizing effects. Overall, the facile LC-Gel microsphere biosensor not only provides a versatile tool for label-free, localized pH monitoring but also opens avenues for investigating the effects of chemical and mechanical stimuli on cellular metabolism within bacterial microenvironments.

DMSPS: Dynamically mixed soft pseudo-label supervision for scribble-supervised medical image segmentation.

High performance of deep learning on medical image segmentation rely on large-scale pixel-level dense annotations, which poses a substantial burden on medical experts due to the laborious and time-consuming annotation process, particularly for 3D images. To reduce the labeling cost as well as maintain relatively satisfactory segmentation performance, weakly-supervised learning with sparse labels has attained increasing attentions. In this work, we present a scribble-based framework for medical image segmentation, called Dynamically Mixed Soft Pseudo-label Supervision (DMSPS). Concretely, we extend a backbone with an auxiliary decoder to form a dual-branch network to enhance the feature capture capability of the shared encoder. Considering that most pixels do not have labels and hard pseudo-labels tend to be over-confident to result in poor segmentation, we propose to use soft pseudo-labels generated by dynamically mixing the decoders' predictions as auxiliary supervision. To further enhance the model's performance, we adopt a two-stage approach where the sparse scribbles are expanded based on predictions with low uncertainties from the first-stage model, leading to more annotated pixels to train the second-stage model. Experiments on ACDC dataset for cardiac structure segmentation, WORD dataset for 3D abdominal organ segmentation and BraTS2020 dataset for 3D brain tumor segmentation showed that: (1) compared with the baseline, our method improved the average DSC from 50.46% to 89.51%, from 75.46% to 87.56% and from 52.61% to 76.53% on the three datasets, respectively; (2) DMSPS achieved better performance than five state-of-the-art scribble-supervised segmentation methods, and is generalizable to different segmentation backbones. The code is available online at: https://github.com/HiLab-git/DMSPS.

Dual-Reference Source-Free Active Domain Adaptation for Nasopharyngeal Carcinoma Tumor Segmentation across Multiple Hospitals.

Nasopharyngeal carcinoma (NPC) is a prevalent and clinically significant malignancy that predominantly impacts the head and neck area. Precise delineation of the Gross Tumor Volume (GTV) plays a pivotal role in ensuring effective radiotherapy for NPC. Despite recent methods that have achieved promising results on GTV segmentation, they are still limited by lacking carefully-annotated data and hard-to-access data from multiple hospitals in clinical practice. Although some unsupervised domain adaptation (UDA) has been proposed to alleviate this problem, unconditionally mapping the distribution distorts the underlying structural information, leading to inferior performance. To address this challenge, we devise a novel Sourece-Free Active Domain Adaptation framework to facilitate domain adaptation for the GTV segmentation task. Specifically, we design a dual reference strategy to select domain-invariant and domain-specific representative samples from a specific target domain for annotation and model fine-tuning without relying on source-domain data. Our approach not only ensures data privacy but also reduces the workload for oncologists as it just requires annotating a few representative samples from the target domain and does not need to access the source data. We collect a large-scale clinical dataset comprising 1057 NPC patients from five hospitals to validate our approach. Experimental results show that our method outperforms the previous active learning (e.g., AADA and MHPL) and UDA (e.g., Tent and CPR) methods, and achieves comparable results to the fully supervised upper bound, even with few annotations, highlighting the significant medical utility of our approach. In addition, there is no public dataset about multi-center NPC segmentation, we will release code and dataset for future research (Git).

Silencing BMAL1 promotes M1/M2 polarization through the LDHA/lactate axis to promote GBM sensitivity to bevacizumab.

OBJECTIVE: Glioblastoma (GBM) has poor clinical prognosis due to limited treatment options. In addition, the current treatment regimens for GBM may only slightly prolong patient survival. The aim of this study was to assess the role of BMAL1 in the immune microenvironment and drug resistance of GBM. METHODS: GBM cell lines with stable BMAL1 knockdown or LDHA overexpression were constructed, and functionally characterized by the CCK8, EdU incorporation, and transwell assays. In vivo GBM model was established in C57BL/6J mice. Flow cytometry, ELISA, immunofluorescence, and RT-qPCR were performed to detect macrophage polarization. Lactate production, pathological changes, and the expression of glycolytic proteins were analyzed by HE staining, immunohistochemistry, biochemical assays, and Western blotting. RESULTS: BMAL1 silencing inhibited the malignant characteristics, lactate production, and expression of glycolytic proteins in GBM cells, and these changes were abrogated by overexpression of LDHA or exogenous lactate supplementation. Furthermore, BMAL1 knockdown induced M1 polarization of macrophages, and inhibited M2 polarization and angiogenesis in GBM cells in conditioned media. Overexpression of LDHA or presence of exogenous lactate inhibited BMAL1-induced M1 polarization and angiogenesis. Finally, BMAL1 silencing and bevacizumab synergistically inhibited glycolysis, angiogenesis and M2 polarization, and promoted M1 polarization in vivo, thereby suppressing GBM growth. CONCLUSION: BMAL1 silencing can sensitize GBM cells to bevacizumab by promoting M1/M2 polarization through the LDHA/lactate axis.

Cross-Domain Mutual-Assistance Learning Framework for Fully Automated Diagnosis of Primary Tumor in Nasopharyngeal Carcinoma.

Accurate T-staging of nasopharyngeal carcinoma (NPC) holds paramount importance in guiding treatment decisions and prognosticating outcomes for distinct risk groups. Regrettably, the landscape of deep learning-based techniques for T-staging in NPC remains sparse, and existing methodologies often exhibit suboptimal performance due to their neglect of crucial domain-specific knowledge pertinent to primary tumor diagnosis. To address these issues, we propose a new cross-domain mutual-assistance learning framework for fully automated diagnosis of primary tumor using H&N MR images. Specifically, we tackle primary tumor diagnosis task with the convolutional neural network consisting of a 3D cross-domain knowledge perception network (CKP net) for excavated cross-domain-invariant features emphasizing tumor intensity variations and internal tumor heterogeneity, and a multi-domain mutual-information sharing fusion network (M2SF net), comprising a dual-pathway domain-specific representation module and a mutual information fusion module, for intelligently gauging and amalgamating multi-domain, multi-scale T-stage diagnosis-oriented features. The proposed 3D cross-domain mutual-assistance learning framework not only embraces task-specific multi-domain diagnostic knowledge but also automates the entire process of primary tumor diagnosis. We evaluate our model on an internal and an external MR images dataset in a three-fold cross-validation paradigm. Exhaustive experimental results demonstrate that our method outperforms the state-of-the-art algorithms, and obtains promising performance for tumor segmentation and T-staging. These findings underscore its potential for clinical application, offering valuable assistance to clinicians in treatment decision-making and prognostication for various risk groups.

Minor hepatectomy combined with cholangioplasty and cholangiojejunostomy for Bismuth II hilar cholangiocarcinoma: A propensity score matching analysis.

BACKGROUND: The optimal surgical approach for Bismuth II hilar cholangiocarcinoma (HCCA) remains controversial. This study compared perioperative and oncological outcomes between minor and major hepatectomy. MATERIALS AND METHODS: One hundred and seventeen patients with Bismuth II HCCA who underwent hepatectomy and cholangiojejunostomy between January 2018 and December 2022 were retrospectively investigated. Propensity score matching created a cohort of 62 patients who underwent minor (n = 31) or major (n = 31) hepatectomy. Perioperative outcomes, complications, quality of life, and survival outcomes were compared between the groups. Continuous data are expressed as the mean ± standard deviation, categorical variables are presented as n (%). RESULTS: Minor hepatectomy had a significantly shorter operation time (245.42 ± 54.31 vs. 282.16 ± 66.65 min; P = 0.023), less intraoperative blood loss (194.19 ± 149.17 vs. 315.81 ± 256.80 mL; P = 0.022), a lower transfusion rate (4 vs. 11 patients; P = 0.038), more rapid bowel recovery (17.77 ± 10.00 vs. 24.94 ± 9.82 h; P = 0.005), and a lower incidence of liver failure (1 vs. 6 patients; P = 0.045). There were no significant between-group differences in wound infection, bile leak, bleeding, pulmonary infection, intra-abdominal fluid collection, and complication rates. Postoperative laboratory values, length of hospital stay, quality of life scores, 3-year overall survival (25.8 % vs. 22.6 %; P = 0.648), and 3-year disease-free survival (12.9 % vs. 16.1 %; P = 0.989) were comparable between the groups. CONCLUSION: In this propensity score-matched analysis, overall survival and disease-free survival were comparable between minor and major hepatectomy in selected patients with Bismuth II HCCA. Minor hepatectomy was associated with a shorter operation time, less intraoperative blood loss, less need for transfusion, more rapid bowel recovery, and a lower incidence of liver failure. Besides, this findings need confirmation in a large-scale, multicenter, prospective randomized controlled trial with longer-term follow-up.

Treatment of Keratosis Lichenoides Chronica With Upadacitinib.

This case report describes a 30-year-old man presenting with 1-year history of nonitchy red papules and patches who was subsequently treated with upadacitinib.

A nomogram based on clinical characteristics and nutritional indicators for relative and absolute weight loss during radiotherapy in initially inoperable patients with locally advanced esophageal squamous cell carcinoma.

OBJECTIVE: Radiation for locally advanced esophageal squamous cell carcinoma often is accompanied by radiation esophagitis, which interferes with oral intake. We aimed to develop a nomogram model to identify initially inoperable patients with relative and absolute weight loss who need prophylactic nutritional supplementation. METHODS: A total of 365 initially inoperable patients with locally advanced esophageal squamous cell carcinoma receiving radiotherapy between January 2018 and December 2022 were included in the study, which was divided into discovery and validation cohorts. Receiver operating characteristic and Kaplan-Meier curve analyses were performed to compare the areas under the curve and survival benefits. RESULTS: A total of 42.2% (154 of 365) of the patients had been diagnosed with cancer cachexia. The malnourished group had a higher interruption rate of radiotherapy and number of complication diseases (P < 0.05). Meanwhile, patients with malnutrition had lower lymphocytes and prognostic nutritional index (P < 0.05). The combined index showed a higher area under the curve value (0.67; P < 0.001) than number of complication diseases (area under the curve = 0.52) and prognostic nutritional index (area under the curve = 0.49) for relative weight loss (≥ 5%). Similarly, the combined index had a higher area under the curve value (0.79; P < 0.001) than number of complication diseases (area under the curve = 0.56), treatment regimens (area under the curve = 0.56), subcutaneous fat thickness (area under the curve = 0.60), pretreatment body weight (area under the curve = 0.61), neutrophils (area under the curve = 0.56), and prognostic nutritional index (area under the curve = 0.50) for absolute weight loss (≥ 5 kg). Absolute and relative weight loss remained independent prognostic factors, with short overall survival rates compared with the normal group (P < 0.05). Patients with high nomogram scores supported by nutritional intervention had less weight loss, better nutrition scores, and increased plasma CD8+ T cells, and interferon gamma. CONCLUSIONS: We developed a nomogram model that was intended to estimate relative and absolute weight loss in initially inoperable patients with locally advanced esophageal squamous cell carcinoma during radiotherapy, which might help facilitate an objective decision on prophylactic nutritional supplementation.

Functionalized sampling swabs array-based portable ATP bioluminescence sensor with on-site enrichment and high specificity for live Salmonella detection.

Live food-borne pathogens, featured with rapid proliferative capacity and high pathogenicity, pose an emerging food safety and public health crisis. The high-sensitivity detection of pathogens is particularly imperative yet remains challenging. This work developed a functionalized nylon swab array with enhanced affinity for Salmonella typhimurium (S.T.) for high-specificity ATP bioluminescence-based S.T. detection. In brief, the nylon swabs (NyS) were turned to N-methylation nylon (NyS-OH) by reacting with formaldehyde, and NyS-OH were further converted to NyS-CA by reacting with carboxylic groups of citric acid (CA) and EDC/NHS solution, for altering the NyS surface energy to favor biomodification. The antibody-immobilized nylon swab (MNyS-Ab) was ready for S.T.-specific adsorption. Three prepared MNyS-Ab were installed on a stirrer to form an MNyS-Ab array, allowing for on-site enrichment of S.T. through absorptive extraction. The enriched S.T. was quantified by measuring the bioluminescence of ATP released from cell lysis utilizing a portable ATP bioluminescence sensor. The bioassay demonstrated a detectable range of 102-107 CFU mL-1 with a detection limit (LOD) of 8 CFU/mL within 35 min. The signal of single MNyS-Ab swabs was 500 times stronger than the direct detection of 106 CFU/mL S.T. The MNyS-Ab array exhibited a 100-fold increase in extraction level compared to a single MNyS. This combination of a portable bioluminescent sensor and modified nylon swab array offers a novel strategy for point-of-care testing of live S.T. strains. It holds promise for high-sensitivity measurements of other pathogens and viruses.

The roles of tissue resident macrophages in health and cancer.

As integral components of the immune microenvironment, tissue resident macrophages (TRMs) represent a self-renewing and long-lived cell population that plays crucial roles in maintaining homeostasis, promoting tissue remodeling after damage, defending against inflammation and even orchestrating cancer progression. However, the exact functions and roles of TRMs in cancer are not yet well understood. TRMs exhibit either pro-tumorigenic or anti-tumorigenic effects by engaging in phagocytosis and secreting diverse cytokines, chemokines, and growth factors to modulate the adaptive immune system. The life-span, turnover kinetics and monocyte replenishment of TRMs vary among different organs, adding to the complexity and controversial findings in TRMs studies. Considering the complexity of tissue associated macrophage origin, macrophages targeting strategy of each ontogeny should be carefully evaluated. Consequently, acquiring a comprehensive understanding of TRMs' origin, function, homeostasis, characteristics, and their roles in cancer for each specific organ holds significant research value. In this review, we aim to provide an outline of homeostasis and characteristics of resident macrophages in the lung, liver, brain, skin and intestinal, as well as their roles in modulating primary and metastatic cancer, which may inform and serve the future design of targeted therapies.

Optimization of collimator angle combined island blocking with parked gap achieves superior normal tissue sparing in SBRT planning of multiple liver lesions.

PURPOSE: To propose an efficient collimator angle optimization method by combining island blocking (IB) and parked gap (PG) problem to reduce the radiotherapy dose for normal tissue. The reduction will be done with single-isocenter multi-lesion volumetric modulated arc therapy (VMAT) for the stereotactic body radiation therapy (SBRT) of liver cancer. METHODS: A novel collimator angle optimization algorithm was developed based on the two-dimensional projection of targets on a beam's eye view (BEV) plane as a function of gantry and collimator angle. This optimization algorithm minimized the sum of the combined IB and PG (IB & PG) areas from all gantry angles for each arc. For comparison, two SBRT plans were respectively generated for each of the 20 retrospective liver cancer cases with multiple lesions. One plan was optimized using the IB & PG algorithm, and the other plan was optimized with a previously reported optimization algorithm that only considered the IB area. Plans were then evaluated and compared using typical dosimetric metrics. RESULTS: With the comparable target coverage, IB & PG plans had significantly lower D500cc, D700cc, mean dose (Dmean), and V15 of normal liver tissues when compared to IB plans. The median percent reductions were 3.32% to 5.36%. The D1cc, D5cc, and Dmean for duodenum and small intestine in IB & PG plans were significantly reduced in a range from 7.60% up to 16.03%. Similarly, the median integral dose was reduced by 3.73%. Furthermore, the percentage of normal liver Dmean sparing when IB & PG plans compared to IB plans, was found to be positively correlated (ρ = 0.669, P = 0.001) with the inter-target distance. CONCLUSION: The proposed IB & PG algorithm has been demonstrated to outperform the IB algorithm in almost all normal tissue sparing, and the magnitude of liver sparing was positively correlated with inter-target distance.

Lymphocytic vasculitis in livedoid vasculopathy: A report of 137 cases.

BACKGROUND: Livedoid vasculopathy (LV) is characterized by fibrin deposition and thrombosis in the small vessels of the superficial dermis. It is widely recognized as an occlusive disease, which is primarily treated with anticoagulation therapy. METHODS: We retrospectively analyzed the clinical and histopathological characteristics of patients diagnosed with LV at a tertiary dermatology department to explore the characteristics of lymphocytic vasculitis in LV. The frequency of vasculitis and the types of vessels involved were examined based on the diameters and elastic fiber distribution of the involved vessels. In addition, the immunophenotypes of infiltrating lymphocytes were analyzed. RESULTS: In a large retrospective series including 358 LV cases, we identified 137 (38.3%) cases of lymphocytic vasculitis. Among them, 48 cases involved medium-sized vessels, including arterioles and venules, whereas 89 cases involved only small vessels. In addition, 12 cases displayed a segmental distribution of vasculitis. The infiltrating lymphocytes were mainly T cells, with dominant cells stained positive for CD4. CONCLUSIONS: Lymphocytic vasculitis forms part of the histological spectrum of LV, affecting both medium-sized and small vessels. It is possible that the occlusion of small vessels may represent a phenomenon secondary to lymphocytic vasculitis.

Long-term outcomes of metastasis-directed stereotactic body radiation therapy in metastatic nasopharyngeal carcinoma.

BACKGROUND: The study aims to evaluate the outcomes of metastasis-directed stereotactic body radiation therapy (SBRT) in metastatic nasopharyngeal carcinoma (mNPC). METHODS: We reviewed all SBRT conducted in patients with mNPC in our institution between 2013 and 2022. Systemic therapy was performed with chemotherapy with or without anti-programmed death-1 (PD-1) therapy. Local treatment delivered with ablative purpose in stereotactic setting with dose/fraction ≥5 Gy was evaluated. Kaplan-Meier analyses were used to determine the rates of local control (LC), progression-free survival (PFS), and overall survival (OS). Univariate and multivariate analyses were performed by Cox regression. RESULTS: A total of 54 patients with 76 metastatic sites receiving SBRT were analyzed. Median follow-up was 49 months. The 3-year LC, PFS, and OS rates were 89.1%, 29.4%, and 57.9%, respectively. Adding a PD-1 inhibitor to SBRT tended to prolong median OS (50.1 vs. 32.2 months, p = 0.068). Patients receiving a biological effective dose (BED, α/ß = 10) ≥ 80 Gy had a significantly longer median OS compared to those who received a lower dose (not reached vs. 29.5 months, p = 0.004). Patients with oligometastases (1-5 metastases) had a better median OS (not reached vs. 29.5 months, p < 0.001) and PFS (34.3 vs. 4.6 months, p < 0.001). Pretreatment EBV-DNA and maintenance therapy were also significant predictors for OS. CONCLUSIONS: Metastatic NPC patients could benefit from metastases-directed SBRT in combination with systemic therapy.

Dosimetric comparison in sparing normal tissue dosage by using auto-SBRT planning in oligo liver tumors.

Purpose: The study aimed to compare the dosimetric distribution of VMAT plans by increasing the number of half arcs in liver SBRT and investigate the effect by using automatic plan software in plan optimization. Method: Thirty-one patients with oligo liver tumors were randomly selected. VMAT treatment plans with different numbers of coplanar half arcs were generated. Result: Adding arcs significantly increased the PTV, D2%, D50%, and CI, but sacrificed the plan homogeneity. It also decreased the maximum dose of normal tissues such as the stomach, duodenum, and spinal cord and reduced Dmean, D500cc, and D700cc for the liver. Nevertheless, the diminishing effect gradually decayed into three arcs. Meanwhile, the addition of arcs substantially extended the beam-on time. Conclusion: In the context of SBRT for oligo liver tumors, increasing the number of coplanar half arcs will improve PTV conformity and offer better protection for OARs, albeit at the expense of increased treatment duration. Considering the trade-off between plan quality and treatment efficiency, a three-arc plan may be more suitable for clinical implementation.

Advancements of radiotherapy for recurrent head and neck cancer in modern era.

Head and neck cancer is a kind of cancer which can be eradicated from radical radiation therapy. However, with best efforts, nearly 40% patients will experience locoregional recurrence. Locoregional recurrence is the main cause of cancer-related death in head and neck cancers, so local treatments play a key role in improving progression free survival. In the last decades, radiation techniques have been tremendously developed, highly conformal radiation techniques such as intensity-modulated radiotherapy, stereotactic body radiation therapy, brachytherapy and proton or heavy ion radiation therapy have their unique radiobiological advances. Although reirradiation is widely used in clinical practice, but little is known when comparing the different techniques. In this review, we will provide a comprehensive overview of the role of reirradiation in recurrent head and neck cancers including radiation techniques, patient selection, overall clinical benefits, and toxicities.

Targeted co-delivery of curcumin and erlotinib by MoS2 nanosheets for the combination of synergetic chemotherapy and photothermal therapy of lung cancer.

BACKGROUND: Curcumin (Cur), a bioactive component of Chinese traditional medicine, has demonstrated inhibitory properties against cancer cell proliferation while synergistically enhancing the anticancer efficacy of erlotinib (Er). However, the individual limitations of both drugs, including poor aqueous solubility, lack of targeting ability, short half-life, etc., and their distinct pharmacokinetic profiles mitigate or eliminate their combined antitumor potential. RESULTS: In this study, we developed a molybdenum disulfide (MoS2)-based delivery system, functionalized with polyethylene glycol (PEG) and biotin, and co-loaded with Cur and Er, to achieve efficient cancer therapy. The MoS2-PEG-Biotin-Cur/Er system effectively converted near-infrared (NIR) light into heat, thereby inducing direct photothermal ablation of cancer cells and promoting controlled release of Cur and Er. Biotin-mediated tumor targeting facilitated the selective accumulation of MoS2-PEG-Biotin-Cur/Er at the tumor site, thus enhancing the synergistic antitumor effects of Cur and Er. Remarkably, MoS2-PEG-Biotin-Cur/Er achieved the combination of synergistic chemotherapy and photothermal therapy (PTT) upon NIR irradiation, effectively suppressing lung cancer cell proliferation and inhabiting tumor growth in vivo. CONCLUSIONS: The as-synthesized MoS2-PEG-Biotin-Cur/Er, featuring high targeting ability, NIR light-responsive drug release, and the integration of synergistic chemotherapy and PTT, may provide a promising strategy for the treatment of lung cancer in clinical practice.

CDDSA: Contrastive domain disentanglement and style augmentation for generalizable medical image segmentation.

Generalization to previously unseen images with potential domain shifts is essential for clinically applicable medical image segmentation. Disentangling domain-specific and domain-invariant features is key for Domain Generalization (DG). However, existing DG methods struggle to achieve effective disentanglement. To address this problem, we propose an efficient framework called Contrastive Domain Disentanglement and Style Augmentation (CDDSA) for generalizable medical image segmentation. First, a disentangle network decomposes the image into domain-invariant anatomical representation and domain-specific style code, where the former is sent for further segmentation that is not affected by domain shift, and the disentanglement is regularized by a decoder that combines the anatomical representation and style code to reconstruct the original image. Second, to achieve better disentanglement, a contrastive loss is proposed to encourage the style codes from the same domain and different domains to be compact and divergent, respectively. Finally, to further improve generalizability, we propose a style augmentation strategy to synthesize images with various unseen styles in real time while maintaining anatomical information. Comprehensive experiments on a public multi-site fundus image dataset and an in-house multi-site Nasopharyngeal Carcinoma Magnetic Resonance Image (NPC-MRI) dataset show that the proposed CDDSA achieved remarkable generalizability across different domains, and it outperformed several state-of-the-art methods in generalizable segmentation. Code is available at https://github.com/HiLab-git/DAG4MIA.