Contaminant Biomagnification in Polar Bears: Interindividual Differences, Dietary Intake Rate, and the Gut Microbiome.

Some persistent hydrophobic pollutants biomagnify, i.e., achieve higher contaminant levels in a predator than in its prey (Cpredator/Cprey > 1). This ratio is called the biomagnification factor (BMF) and is traditionally determined using tissues from carcasses or biopsies. Using a noninvasive method that relies on equilibrium sampling in silicone-film-coated vessels and chemical analysis of paired diet and feces, we determined on three occasions the thermodynamic biomagnification limit (BMFlim) and feces-based biomagnification factor (BMFF) for three zoo-housed polar bears who experience seasonal periods of hyperphagia and hypophagia. All bears had high biomagnification capabilities (BMFlim was up to 200) owing to very efficient lipid assimilation (up to 99.5%). The bears differed up to a factor of 3 in their BMFlim. BMFlim and BMFF of a bear increased by up to a factor of 4 during the hypophagic period, when the ingestion rate was greatly reduced. Much of that variability can be explained by differences in the lipid assimilation efficiency, even though this efficiency ranged only from 98.1 to 99.5%. A high BMFlim was associated with a high abundance of Bacteroidales and Lachnospirales in the gut microbiome. Biomagnification varies to a surprisingly large extent between individuals and within the same individual over time. Future work should investigate whether this can be attributed to the influence of the gut microbiome on lipid assimilation by studying more individual bears at different key physiological stages.

Mechanisms of Neuronal Reactivation in Memory Consolidation: A Perspective from Pathological Conditions.

Memory consolidation refers to a process by which labile newly formed memory traces are progressively strengthened into long term memories and become more resistant to interference. Recent work has revealed that spontaneous hippocampal activity during rest, commonly referred to as "offline" activity, plays a critical role in the process of memory consolidation. Hippocampal reactivation occurs during sharp-wave ripples (SWRs), which are events associated with highly synchronous neural firing in the hippocampus and modulation of neural activity in distributed brain regions. Memory consolidation occurs primarily through a coordinated communication between hippocampus and neocortex. Cortical slow oscillations drive the repeated reactivation of hippocampal memory representations together with SWRs and thalamo-cortical spindles, inducing long-lasting cellular and network modifications responsible for memory stabilization.In this review, we aim to comprehensively cover the field of "reactivation and memory consolidation" research by detailing the physiological mechanisms of neuronal reactivation and firing patterns during SWRs and providing a discussion of more recent key findings. Several mechanistic explanations of neuropsychiatric diseases propose that impaired neural replay may underlie some of the symptoms of the disorders. Abnormalities in neuronal reactivation are common phenomenon and cause pathology impairment in several diseases, such as Alzheimer's disease (AD), temporal lobe epilepsy (TLE), and schizophrenia. However, the specific physiological mechanisms and pathological changes of reactivation in each disease are different. Recent work has also enlightened some of the underlying pathological mechanisms of neuronal reactivation in these diseases. In this review, we further describe how SWRs, ripples, and slow oscillations are affected in Alzheimer's disease, epilepsy, and schizophrenia. We then compare the differences of neuronal reactivation and discuss how different reactivation abnormalities cause pathological changes in these diseases. Aberrant neural reactivation provides insights into disease pathogenesis and may even serve as biomarkers for early disease progression and treatment response.

High dimensional proteomic mapping of bone marrow immune characteristics in immune thrombocytopenia.

To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia (ITP), this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight (CyTOF). Thirty-six patients with ITP and nine healthy volunteers were enrolled in the study. As soluble immunomodulatory molecules, more sCD25 and sGalectin-9 were detected in ITP patients. On the cell surface, co-stimulatory molecules like ICOS and HVEM were observed to be upregulated in mainly central memory and effector T cells. In contrast, co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th17 cell subsets. Taking a platelet count of 30×109 L-1 as the cutoff value, ITP patients with high and low platelet counts showed different T cell immune profiles. Antigen-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions, respectively, and participate in the pathogenesis of ITP. In conclusion, the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of ITP. They may offer novel targets to develop personalized immunotherapies.

Cerastecins inhibit membrane lipooligosaccharide transport in drug-resistant Acinetobacter baumannii.

Carbapenem-resistant Acinetobacter baumannii infections have limited treatment options. Synthesis, transport and placement of lipopolysaccharide or lipooligosaccharide (LOS) in the outer membrane of Gram-negative bacteria are important for bacterial virulence and survival. Here we describe the cerastecins, inhibitors of the A. baumannii transporter MsbA, an LOS flippase. These molecules are potent and bactericidal against A. baumannii, including clinical carbapenem-resistant Acinetobacter baumannii isolates. Using cryo-electron microscopy and biochemical analysis, we show that the cerastecins adopt a serpentine configuration in the central vault of the MsbA dimer, stalling the enzyme and uncoupling ATP hydrolysis from substrate flipping. A derivative with optimized potency and pharmacokinetic properties showed efficacy in murine models of bloodstream or pulmonary A. baumannii infection. While resistance development is inevitable, targeting a clinically unexploited mechanism avoids existing antibiotic resistance mechanisms. Although clinical validation of LOS transport remains undetermined, the cerastecins may open a path to narrow-spectrum treatment modalities for important nosocomial infections.

The feasibility and clinical significance of lateral approach thyroidectomy.

BACKGROUND: By comparing the three lateral approaches to thyroidectomy, the feasibility and clinical effects were analyzed, and the advantages of the lateral approach were summarized. METHODS: From January 2022 to January 2023, 52 patients with thyroid cancer admitted to our department were selected and subjected to Lateral approach for thyroidectomy. Among them, 31 patients underwent thyroidectomy via the supraclavicular approach, 13 patients underwent endoscopic thyroidectomy via the subclavicular approach, and 8 patients underwent endoscopic thyroidectomy via the axillary approach. The basic conditions, surgical conditions, complications, postoperative pain scores and postoperative satisfaction of patients in the three approach surgery groups were recorded and analyzed. RESULTS: There were no significant differences among the three approach groups in terms of patient characteristics, number of central lymph node dissections, intraoperative blood loss, postoperative drainage volume, duration of drainage tube placement, length of hospital stay, postoperative pain, satisfaction, and complications. However, the operation time was longest in the subclavicular approach group, followed by the axillary approach group, and shortest in the supraclavicular approach group. The total hospitalization cost was highest in the axillary approach group, followed by the subclavicular approach group, and lowest in the supraclavicular approach group. CONCLUSION: The lateral approach for thyroidectomy is deemed a safe and effective method. The three different approach paths gradually increase in length, allowing for the accumulation of anatomical experience. This approach has a shorter learning curve for clinical doctors and is a favorable choice for patients seeking aesthetic benefits.

Mendelian randomization study shows no causal relationship between psychiatric disorders and glaucoma in European and East Asian populations.

Background: Glaucoma is a leading cause of blindness strongly associated with psychiatric disorders, but the causal association between glaucoma and psychiatric disorders remains uncertain because of the susceptibility of observational studies to confounding and reverse causation. This study aims to explore the potential causal association between glaucoma and three highly related psychiatric disorders (Depression, Insomnia, and Schizophrenia) in the European and East Asian populations using a two-sample Mendelian randomization analysis. Methods: Instrumental variables (IVs) of depression, insomnia, and schizophrenia in the European population were obtained after strict filtering. Summary-level data for glaucoma and glaucoma subtypes (primary open-angle glaucoma and primary closed-angle glaucoma) were obtained as outcomes. The inverse variance weighting (IVW) method was used as the primary method. Additionally, the causal effect was evaluated in the East Asian population using the same methods to validate analysis results. The robustness of these results was confirmed using heterogeneity, pleiotropy, and Steiger directionality test. Results: The primary MR results indicated that genetically driven psychiatric disorders were not causally associated with glaucoma (Depression: odds ratio (OR): 1.15, 95% confidence interval (CI): 0.93-1.42, p = 0.20; Insomnia: OR: 1.14, 95% CI: 0.63-2.05, p = 0.66; Schizophrenia: OR: 1.00, 95% CI: 0.93-1.08, p = 0.95), either with the risk of glaucoma subtypes in the European population. Meanwhile, results in the East Asian population were consistent with the results among the European population (Depression: OR = 1.38, CI 0.75-2.53, p = 0.30; Insomnia: OR = 0.99, CI 0.83-1.18, p = 0.93; Schizophrenia: OR = 1.06, CI 0.94-1.20, p = 0.34) with similar causal estimates in direction. Consistency was obtained by corroborating with other supporting methods. Besides, the robustness of the results was proved and the directionality test confirmed our estimation of potential causal direction (p < 0.001). Conclusion: This study found a non-causal association between psychiatric disorders and the risk of glaucoma in the European and East Asian populations, which contradicts many existing observational reports, indicating that increased psychiatric disorders in glaucoma patients were more likely modifiable rather not inheritable.

Suppression of NSCLC progression via the co-administration of Danusertib, an AURK inhibitor, and KRIBB11, an HSF1 inhibitor.

Aurora kinase (AURK) and heat shock factor 1 (HSF1) are commonly overexpressed in non-small cell lung cancer (NSCLC), correlating with poor prognosis. This study aims to assess the therapeutic potential of combining the Danusertib (Danu, AURK inhibitor) and KRIBB11 (HSF1 inhibitor) for NSCLC treatment. The effects of this combination were investigated in A549 cells and a tumor xenograft mouse model. The findings demonstrate that concurrent administration of Danu and KRIBB11 effectively impedes cell proliferation, induces apoptosis, and triggers G2/M cell cycle arrest. Moreover, the combination treatment upregulates pro-apoptotic proteins (Cleaved-caspase3, Cleaved-PARP, and Bax) while downregulating anti-apoptotic proteins (Bcl-2), as well as G2/M-related proteins (CDC2 and cyclin B1). Additionally, the combination treatment elevates reactive oxygen species (ROS) levels, decreases mitochondrial membrane potential, and activates the DNA damage pathway. Interestingly, we discovered that the PI3K/AKT pathway is involved in mediating the effects of both Danu and KRIBB11. Furthermore, the combination treatment inhibits tumor growth and AKT signaling in the xenograft mouse model, increases levels of the tumor tissue oxidation product malondialdehyde (MDA), and induces DNA damage. To summarize, a potential therapeutic approach for NSCLC may involve dual inhibition of AURK and HSF1, resulting in the downregulation of the PI3K/AKT signaling pathway, and the activation of ROS-mediated mitochondrial and DNA damage pathways.

SET domain containing 2 promotes megakaryocyte polyploidization and platelet generation through methylation of α-tubulin.

BACKGROUND: Megakaryocytes (MKs) are polyploid cells responsible for producing ∼1011 platelets daily in humans. Unraveling the mechanisms regulating megakaryopoiesis holds the promise for the production of clinical-grade platelets from stem cells, overcoming significant current limitations in platelet transfusion medicine. Previous work identified that loss of the epigenetic regulator SET domain containing 2 (SETD2) was associated with an increased platelet count in mice. However, the role of SETD2 in megakaryopoiesis remains unknown. OBJECTIVES: Here, we examined how SETD2 regulated MK development and platelet production using complementary murine and human systems. METHODS: We manipulated the expression of SETD2 in multiple in vitro and ex vivo models to assess the ploidy of MKs and the function of platelets. RESULTS: The genetic ablation of Setd2 increased the number of high-ploidy bone marrow MKs. Peripheral platelet counts in Setd2 knockout mice were significantly increased ∼2-fold, and platelets exhibited normal size, morphology, and function. By knocking down and overexpressing SETD2 in ex vivo human cell systems, we demonstrated that SETD2 negatively regulated MK polyploidization by controlling methylation of α-tubulin, microtubule polymerization, and MK nuclear division. Small-molecule inactivation of SETD2 significantly increased the production of high-ploidy MKs and platelets from human-induced pluripotent stem cells and cord blood CD34+ cells. CONCLUSION: These findings identify a previously unrecognized role for SETD2 in regulating megakaryopoiesis and highlight the potential of targeting SETD2 to increase platelet production from human cells for transfusion practices.

Region-specific transcriptomic responses to obesity and diabetes in macaque hypothalamus.

The hypothalamus plays a crucial role in the progression of obesity and diabetes; however, its structural complexity and cellular heterogeneity impede targeted treatments. Here, we profiled the single-cell and spatial transcriptome of the hypothalamus in obese and sporadic type 2 diabetic macaques, revealing primate-specific distributions of clusters and genes as well as spatial region, cell-type-, and gene-feature-specific changes. The infundibular (INF) and paraventricular nuclei (PVN) are most susceptible to metabolic disruption, with the PVN being more sensitive to diabetes. In the INF, obesity results in reduced synaptic plasticity and energy sensing capability, whereas diabetes involves molecular reprogramming associated with impaired tanycytic barriers, activated microglia, and neuronal inflammatory response. In the PVN, cellular metabolism and neural activity are suppressed in diabetic macaques. Spatial transcriptomic data reveal microglia's preference for the parenchyma over the third ventricle in diabetes. Our findings provide a comprehensive view of molecular changes associated with obesity and diabetes.

Composite of carbon dots and TiNiSn thermoelectric materials: Initial investigation on the electrical and thermal transport properties.

TiNiCu0.025Sn0.99Sb0.01 is prepared using microwaves. However, an ultra-high electrical conductivity and electronic thermal conductivity are obtained by interstitial Cu and Sb doping, which could not effectively improve the ZT value. We introduce carbon dots (CDs) as a nano-second phase by ball milling to simultaneously optimize the thermoelectric properties. To our best knowledge, this is the first report on half-Heusler/CDs composites. Experimental results show that the introduction of nano-CDs optimizes the carrier concentration and mobility and dramatically improves the Seebeck coefficient through the energy filtering effect. The nano-CDs introduce more point defects, inhibit the grains growth, and form a specific carbon solid solution second phase in the matrix. The lattice thermal conductivity is reduced to the same level as TiNiSn at 1.96 W m-1 K-1 through the synergistic effect of point defects and phase and grain boundaries scattering, and the ZT value reaches a maximum of 0.63 at 873 K.

Promoting threshold voltage of P2-Na0.67Ni0.33Mn0.67O2 with Cu2+ cation doping toward high-stability cathode for sodium-ion battery.

P2-type Na0.67Ni0.33Mn0.67O2 has attracted considerable attraction as a cathode material for sodium-ion batteries owing to its high operating voltage and theoretical specific capacity. However, when the charging voltage is higher than 4.2 V, the Na0.67Ni0.33Mn0.67O2 cathode undergoes a detrimental irreversible phase transition of P2-O2, leading to a drastic decrease in specific capacity. To address this challenge, we implemented a Cu-doping strategy (Na0.67Ni0.23Cu0.1Mn0.67O2) in this work to stabilize the structure of the transition metal layer. The stabilization strategy involved reinforcing the transition metal-oxygen (TMO) bonds, particularly the MnO bond and inhibiting interlayer slip during deep desodiation. As a result, the irreversible phase transition voltage is delayed, with the threshold voltage increasing from 4.2 to 4.4 V. Ex-situ X-ray diffraction measurements revealed that the Na0.67Ni0.23Cu0.1Mn0.67O2 cathode maintains the P2 phase within the voltage window of 2.5-4.3 V, whereas the P2-Na0.67Ni0.33Mn0.67O2 cathode transforms entirely into O2-type Na0.67Ni0.33Mn0.67O2 when the voltage exceeds 4.3 V. Furthermore, absolute P2-O2 phase transition of the Na0.67Ni0.23Cu0.1Mn0.67O2 cathode occurred at 4.6 V, indicating that Cu2+ doping enhances the stability of the layer structure and increases the threshold voltage. The resulting Na0.67Ni0.23Cu0.1Mn0.67O2 cathode exhibited superior electrochemical properties, demonstrating an initial reversible specific capacity of 89.1 mAh/g at a rate of 2C (360 mA g-1) and retaining more than 78 % of its capacity after 500 cycles.

MRI-Based Radiomics and Deep Learning in Biological Characteristics and Prognosis of Hepatocellular Carcinoma: Opportunities and Challenges.

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third leading cause of cancer-related death worldwide. HCC exhibits strong inter-tumor heterogeneity, with different biological characteristics closely associated with prognosis. In addition, patients with HCC often distribute at different stages and require diverse treatment options at each stage. Due to the variability in tumor sensitivity to different therapies, determining the optimal treatment approach can be challenging for clinicians prior to treatment. Artificial intelligence (AI) technology, including radiomics and deep learning approaches, has emerged as a unique opportunity to improve the spectrum of HCC clinical care by predicting biological characteristics and prognosis in the medical imaging field. The radiomics approach utilizes handcrafted features derived from specific mathematical formulas to construct various machine-learning models for medical applications. In terms of the deep learning approach, convolutional neural network models are developed to achieve high classification performance based on automatic feature extraction from images. Magnetic resonance imaging offers the advantage of superior tissue resolution and functional information. This comprehensive evaluation plays a vital role in the accurate assessment and effective treatment planning for HCC patients. Recent studies have applied radiomics and deep learning approaches to develop AI-enabled models to improve accuracy in predicting biological characteristics and prognosis, such as microvascular invasion and tumor recurrence. Although AI-enabled models have demonstrated promising potential in HCC with biological characteristics and prognosis prediction with high performance, one of the biggest challenges, interpretability, has hindered their implementation in clinical practice. In the future, continued research is needed to improve the interpretability of AI-enabled models, including aspects such as domain knowledge, novel algorithms, and multi-dimension data sources. Overcoming these challenges would allow AI-enabled models to significantly impact the care provided to HCC patients, ultimately leading to their deployment for clinical use. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

MdMYB44-like positively regulates salt and drought tolerance via the MdPYL8-MdPP2CA module in apple.

Abscisic acid (ABA) is involved in salt and drought stress responses, but the underlying molecular mechanism remains unclear. Here, we demonstrated that the overexpression of MdMYB44-like, an R2R3-MYB transcription factor, significantly increases the salt and drought tolerance of transgenic apples and Arabidopsis. MdMYB44-like inhibits the transcription of MdPP2CA, which encodes a type 2C protein phosphatase that acts as a negative regulator in the ABA response, thereby enhancing ABA signaling-mediated salt and drought tolerance. Furthermore, we found that MdMYB44-like and MdPYL8, an ABA receptor, form a protein complex that further enhances the transcriptional inhibition of the MdPP2CA promoter by MdMYB44-like. Significantly, we discovered that MdPP2CA can interfere with the physical association between MdMYB44-like and MdPYL8 in the presence of ABA, partially blocking the inhibitory effect of the MdMYB44-like-MdPYL8 complex on the MdPP2CA promoter. Thus, MdMYB44-like, MdPYL8, and MdPP2CA form a regulatory loop that tightly modulates ABA signaling homeostasis under salt and drought stress. Our data reveal that MdMYB44-like precisely modulates ABA-mediated salt and drought tolerance in apples through the MdPYL8-MdPP2CA module.

Unveiling the nitrogen and phosphorus removal potential: Comparative analysis of three coastal wetland plant species in lab-scale constructed wetlands.

It is well accepted that tidal wetland vegetation performs a significant amount of water filtration for wetlands. However, there is currently little information on how various wetland plants remove nitrogen (N) and phosphorus (P) and how they differ in their denitrification processes. This study compared and investigated the denitrification and phosphorus removal effects of three typical wetland plants in the Yangtze River estuary wetland (Phragmites australis, Spartina alterniflora, and Scirpus mariqueter), as well as their relevant mechanisms, using an experimental laboratory-scale horizontal subsurface flow constructed wetland (CW). The results showed that all treatment groups with plants significantly reduced N pollutants as compared to the control group without plants. In comparison to S. mariqueter (77.2-83.2%), S. alterniflora and P. australis had a similar total nitrogen (TN)removal effectiveness of nearly 95%. With a removal effectiveness of over 99% for ammonium nitrogen (NH4+-N), P. australis outperformed S. alterniflora (95.6-96.8%) and S. mariqueter (94.6-96.5%). The removal of nitrite nitrogen (NO2--N)and nitrate nitrogen (NO3--N)from wastewater was significantly enhanced by S. alterniflora compared to the other treatment groups. Across all treatment groups, the removal rate of PO43--P was greater than 95%. P. australis and S. alterniflora considerably enriched more 15N than S. mariqueter, according to the results of the 15N isotope labeling experiment. While the rhizosphere and bulk sediments of S. alterniflora were enriched with more simultaneous desulfurization-denitrification bacterial genera (such as Paracoccus, Sulfurovum, and Sulfurimonas), which have denitrification functions, the rhizosphere and bulk sediments of P. australis were enriched with more ammonia-oxidizing archaea and ammonia-oxidizing bacteria. As a result, compared to the other plants, P. australis and S. alterniflora demonstrate substantially more significant ability to remove NH4+-N and NO2--N/NO3--N from simulated domestic wastewater.

Habitat Radiomics Based on MRI for Predicting Platinum Resistance in Patients with High-Grade Serous Ovarian Carcinoma: A Multicenter Study.

RATIONALE AND OBJECTIVES: This study aims to explore the feasibility of MRI-based habitat radiomics for predicting response of platinum-based chemotherapy in patients with high-grade serous ovarian carcinoma (HGSOC), and compared to conventional radiomics and deep learning models. MATERIALS AND METHODS: A retrospective study was conducted on HGSOC patients from three hospitals. K-means algorithm was used to perform clustering on T2-weighted images (T2WI), contrast-enhanced T1-weighted images (CE-T1WI), and apparent diffusion coefficient (ADC) maps. After feature extraction and selection, the radiomics model, habitat model, and deep learning model were constructed respectively to identify platinum-resistant and platinum-sensitive patients. A nomogram was developed by integrating the optimal model and clinical independent predictors. The model performance and benefit was assessed using the area under the receiver operating characteristic curve (AUC), net reclassification index (NRI), and integrated discrimination improvement (IDI). RESULTS: A total of 394 eligible patients were incorporated. Three habitats were clustered, a significant difference in habitat 2 (weak enhancement, high ADC values, and moderate T2WI signal) was found between the platinum-resistant and platinum-sensitive groups (P < 0.05). Compared to the radiomics model (0.640) and deep learning model (0.603), the habitat model had a higher AUC (0.710). The nomogram, combining habitat signatures with a clinical independent predictor (neoadjuvant chemotherapy), yielded a highest AUC (0.721) among four models, with positive NRI and IDI. CONCLUSION: MRI-based habitat radiomics had the potential to predict response of platinum-based chemotherapy in patients with HGSOC. The nomogram combining with habitat signature had a best performance and good model gains for identifying platinum-resistant patients.

Highly porous BiOBr@NU-1000 Z-scheme heterojunctions for synergistic efficient adsorption and photocatalytic degradation of tetracycline.

Designing an effective photoactive heterojunction having dual benefits towards photoenergy conversion and pollutant adsorption is regarded as an affordable, green method for eliminating tetracycline (TC) from wastewater. In this regard, a series of BiOBr@NU-1000 (BNU-X, X = 1, 2 and 3) heterojunction photocatalysts are constructed. BNU-X preserves the original skeleton structure of the parent NU-1000, and its high porosity and specific surface area enable superior TC adsorption. At the same time, BNU-X is an effective Z-scheme photocatalyst that improves light trapping, promotes photoelectron-hole separation, and shows excellent photocatalytic degradation efficiency towards TC with the value of the photodegradation kinetic rate constant k being 2.2 and 24.8 times those of NU-1000 and BiOBr, respectively. The significant increase in the photocatalytic activity is ascribed to the construction of an efficient Z-scheme photocatalyst, which promotes the formation of superoxide radicals (˙O2-) and singlet oxygen (1O2) as the main oxidative species in the oxidation system. This research has the advantage of possibilities for the development of porous Z-scheme photocatalysts based on photoactive MOF materials and inorganic semiconductors for the self-purification and photodegradation of organic contaminants.

Ultrasonography - a novel auxiliary interpretive approach for tuberculin-purified pure protein derivative skin test: a comparative study.

BACKGROUND: The tuberculin-purified protein derivative (PPD) test is commonly used as a screening tool for tuberculosis (TB). However, the traditional judgment standard of the PPD test is influenced by subjective factors, which can lead to less accurate and intuitive test results. OBJECTIVES: To evaluate the accuracy of ultrasonography as a novel auxiliary judgment method for the tuberculin-PPD test and its clinical application. DESIGN: This study was designed as a comparative study following the STROBE guidance. METHODS: From February to May 2022, 208 patients with active tuberculosis infection were enrolled. Manual judgment and ultrasonography were employed in a double-blind-utilized manner, and the PPD examination results were recorded. Kappa statistic was performed to measure the concordance between the two diagnostic methods. Fisher's exact test was used for the analyses of the PPD test results of all 208 active tuberculosis infection patients' PPD results. RESULTS: There was a significant difference between the two methods in the PPD result judgment (p < 0.001), particularly in the positive ratio of the PPD test results, (p < 0.05). Overall, 50 patients were determined as PPD positive based on manual judgment. However, only 24 patients' PPD test results were determined as positive via ultrasonography. The remaining 26 patients should have been classified as strong positive but were misclassified as positive. The misdiagnosis ratio was 52% (26/50). CONCLUSION: Ultrasonography has superior accuracy to traditional manual judgment. Moreover, it does not rely on sophisticated clinical experience or training and can reveal subtle changes of the skin corresponding to each PPD test result providing intuitive results. In conclusion, ultrasonography can be used as an auxiliary interpretive approach for PPD test and has a promising future for clinical application.