Meibomian glands segmentation in infrared images with limited annotation.

AIM: To investigate a pioneering framework for the segmentation of meibomian glands (MGs), using limited annotations to reduce the workload on ophthalmologists and enhance the efficiency of clinical diagnosis. METHODS: Totally 203 infrared meibomian images from 138 patients with dry eye disease, accompanied by corresponding annotations, were gathered for the study. A rectified scribble-supervised gland segmentation (RSSGS) model, incorporating temporal ensemble prediction, uncertainty estimation, and a transformation equivariance constraint, was introduced to address constraints imposed by limited supervision information inherent in scribble annotations. The viability and efficacy of the proposed model were assessed based on accuracy, intersection over union (IoU), and dice coefficient. RESULTS: Using manual labels as the gold standard, RSSGS demonstrated outcomes with an accuracy of 93.54%, a dice coefficient of 78.02%, and an IoU of 64.18%. Notably, these performance metrics exceed the current weakly supervised state-of-the-art methods by 0.76%, 2.06%, and 2.69%, respectively. Furthermore, despite achieving a substantial 80% reduction in annotation costs, it only lags behind fully annotated methods by 0.72%, 1.51%, and 2.04%. CONCLUSION: An innovative automatic segmentation model is developed for MGs in infrared eyelid images, using scribble annotation for training. This model maintains an exceptionally high level of segmentation accuracy while substantially reducing training costs. It holds substantial utility for calculating clinical parameters, thereby greatly enhancing the diagnostic efficiency of ophthalmologists in evaluating meibomian gland dysfunction.

Cell-Penetrating Drug Carrier by Molecular Recognition of Sphingomyelin on Plasma Membranes.

Plasma membranes not only maintain the intracellular microenvironment through their phospholipid bilayer but also eliminate exogenous compounds outside the cell membranes. Most drugs especially with high polarity are prevented from entering into cells to exert their effects. Therefore, it is of great significance to design effective drug carriers with a penetrating ability toward plasma membranes. In this study, a dual-templated MIP (dt-MIPs) carrier with controllable microstructure and high drug loading capacity was prepared using highly expressed sphingomyelin on the plasma membrane and tenofovir (TFV), a first-line drug for HIV and chronic hepatitis B, as template molecules. The drug release experiments performed in vitro under simulated physiological conditions demonstrated that sustained and stable adsorption of TFV on dt-MIPs was more than 80% over 50 h. By a combination of flow cytometry and confocal microscopy, dt-MIPs were found to have efficient cell permeability. Furthermore, mass-spectrometry-based intracellular pharmacokinetic studies demonstrated that TFV was delivered completely into cells within 30 min with the delivery of dt-MIPs. The study presented above suggested that dt-MIPs are expected to be alternative nanoscale drug carriers for enhanced drug permeability and controlled release.

Global climate change: Effects of future temperatures on emergency department visits for mental disorders in Beijing, China.

Rising temperatures can increase the risk of mental disorders. As climate change intensifies, the future disease burden due to mental disorders may be underestimated. Using data on the number of daily emergency department visits for mental disorders at 30 hospitals in Beijing, China during 2016-2018, the relationship between daily mean temperature and such visits was assessed using a quasi-Poisson model integrated with a distributed lag nonlinear model. Emergency department visits for mental disorders attributed to temperature changes were projected using 26 general circulation models under four climate change scenarios. Stratification analyses were then conducted by disease subtype, sex, and age. The results indicate that the temperature-related health burden from mental disorders was projected to increase consistently throughout the 21st century, mainly driven by high temperatures. The future temperature-related health burden was higher for patients with mental disorders due to the use of psychoactive substances and schizophrenia as well as for women and those aged <65 years. These findings enhance our knowledge of how climate change could affect mental well-being and can be used to advance and refine targeted approaches to mitigating and adapting to climate change with a view on addressing mental disorders.

Migrasomes from adipose derived stem cells enrich CXCL12 to recruit stem cells via CXCR4/RhoA for a positive feedback loop mediating soft tissue regeneration.

BACKGROUND: Adipose-derived stem cells (ASCs) represent the most advantageous choice for soft tissue regeneration. Studies proved the recruitment of ASCs post tissue injury was mediated by chemokine CXCL12, but the mechanism by which CXCL12 is generated after tissue injury remains unclear. Migrasomes are newly discovered membrane-bound organelles that could deliver CXCL12 spatially and temporally in vivo. In this study, we sought to investigate whether migrasomes participate ASC-mediated tissue regeneration. METHODS: Discrepant and asymmetrical soft tissue regeneration mice model were established, in which HE staining, immunofluorescent staining, western blot and qPCR were conducted to confirm the role of CXCL12 and migrasomes in ASC-mediated tissue regeneration. Characterization of ASC-derived migrasomes were carried out by confocal microscopy, scanning electron microscopy, transmission electron microscopy as well as western blot analysis. The function and mechanism of migrasomes were further testified by assisting tissue regeneration with isolated migrasomes in vivo and by in vitro transwell combined with co-culture system. RESULTS: Here, we show for the first time that migrasomes participate in soft tissue regeneration. ASCs generate migrasomes enriched with CXCL12 to mediate tissue regeneration. Migrasomes from ASCs could promote stem cells migration by activating CXCR4/RhoA signaling in vivo and in vitro. Chemoattracted ASCs facilitate regeneration, as demonstrated by the upregulation of an adipogenesis-associated protein. This positive feed-back-loop creates a favorable microenvironment for soft tissue regeneration. Thus, migrasomes represent a new therapeutic target for ASC-mediated tissue regeneration. CONCLUSIONS: Our findings reveal a previously unknown function of ASCs in mediating tissue regeneration by generating migrasomes. The ASC-derived migrasomes can restore tissue regeneration by recruiting stem cells, which highlighting the potential application of ASC-derived migrasomes in regenerative medicine.

Rising Incidence of Acute Epiglottitis in Eastern China: An Eight-Year Retrospective Study and Its Association with the 24 Solar Terms.

Purpose: This study aimed to investigate the clinical characteristics of acute epiglottitis (AE) patients in East China and examine the correlation between the incidence of AE and the 24 solar terms (24 STs). Methods: A retrospective, observational study was conducted on patients diagnosed with AE between January 2014 and December 2021 at a single-center medical institution in East China. The clinical characteristics of patients with AE and their correlation with the 24 STs were investigated. Results: A total of 287 patients with AE were included in this study, among which there were 179 males (62.37%) and 108 females (37.63%), with a mean age of 47.79 ± 13.83 years (range 16-87 years). Of these patients, 100 (34.84%) had at least one comorbidity and the most common comorbidities were hypertension, smoking and type 2 diabetes. The duration of hospitalization was 3 days (IQR, 1-16 days). All patients, except for one who required tracheal intubation, were cured with intravenous antibiotic administration and the combined use of corticosteroids. The incidence of AE showed significant fluctuations between the 24 STs and the highest number of cases occurred during the Summer solstice (24 cases, 8.36%). Conclusion: The incidence of AE was seen to increase annually in this study. The main features of AE are sore throat, dysphagia, odynophagia and fever, which may be accompanied by inflammation in surrounding areas. A clear correlation exists between the incidence of AE and the fluctuations within the 24 STs, notably with the peak incidence observed during the Summer solstice, which approximately corresponds to June 21 to July 7 in the Gregorian calendar.

Ant-eating spiders from Xizang, China (Araneae, Zodariidae).

Six species of the ant-eating spider of the family Zodariidae are described from Xizang, China, including five new species: Asceuachayusp. nov. (♀), A.dawaisp. nov. (♂♀), Mallinellamigusp. nov. (♂), M.mеdogsp. nov. (♂♀), and M.yadongsp. nov. (♂♀). The female of Cydrelalinzhiensis (Hu, 2001) is described here for the first time. Descriptions and photographs of all the species are provided.

Vascular smooth muscle-specific LRRC8A knockout ameliorates angiotensin II-induced cerebrovascular remodeling by inhibiting the WNK1/FOXO3a/MMP signaling pathway.

Hypertensive cerebrovascular remodeling involves the enlargement of vascular smooth muscle cells (VSMCs), which activates volume-regulated Cl- channels (VRCCs). The leucine-rich repeat-containing family 8 A (LRRC8A) has been shown to be the molecular identity of VRCCs. However, its role in vascular remodeling during hypertension is unclear. In this study, we used vascular smooth muscle-specific LRRC8A knockout (CKO) mice and an angiotensin II (Ang II)-induced hypertension model. The results showed that cerebrovascular remodeling during hypertension was ameliorated in CKO mice, and extracellular matrix (ECM) deposition was reduced. Based on the RNA-sequencing analysis of aortic tissues, the level of matrix metalloproteinases (MMPs), such as MMP-9 and MMP-14, were reduced in CKO mice with hypertension, which was further verified in vivo by qPCR and immunofluorescence analysis. Knockdown of LRRC8A in VSMCs inhibited the Ang II-induced upregulation of collagen I, fibronectin, and matrix metalloproteinases (MMPs), and overexpression of LRRC8A had the opposite effect. Further experiments revealed an interaction between with-no-lysine (K)-1 (WNK1), which is a "Cl--sensitive kinase", and Forkhead transcription factor O3a (FOXO3a), which is a transcription factor that regulates MMP expression. Ang II induced the phosphorylation of WNK1 and downstream FOXO3a, which then increased the expression of MMP-2 and MMP-9. This process was inhibited or potentiated when LRRC8A was knocked down or overexpressed, respectively. Overall, these results demonstrate that LRRC8A knockout in vascular smooth muscle protects against cerebrovascular remodeling during hypertension by reducing ECM deposition and inhibiting the WNK1/FOXO3a/MMP signaling pathway, demonstrating that LRRC8A is a potential therapeutic target for vascular remodeling-associated diseases such as stroke.

Exploration of a somatosensory interactive assessment tool for children with intellectual disabilities.

Based on the functional assessment concept and embodied assessment requirements, the present study aimed to design and develop an assessment tool for children with intellectual disabilities with the help of somatosensory interactive (SI) technology. The sample in this study consisted of 73 children with intellectual disabilities and 70 children with typical development. Data were collected through three SI tasks, four traditional executive function tasks, and user experience interviews to analyse the effectiveness of the SI assessment tool. The results showed that the SI assessment tool had good scale validity, discriminant validity, and the ability to identify intellectual disabilities. Children preferred SI tasks and showed higher involvement and more positive emotions. The SI tool with three SI tasks is a more scientific, effective, and advanced tool for assessing children with intellectual disabilities.

An NIR-II-emitting type-I photosensitizer for efficient hypoxic tumor phototheranostics.

A small molecule-based NIR-II type-I photosensitizer (IT-IC) with a strong push-pull effect and good planar π-conjugated structure was synthesized. The IT-IC NPs exhibited strong light absorption, outstanding NIR-II fluorescence emission, excellent photothermal conversion and efficient type-I/II ROS generation, showing encouraging therapeutic outcomes for hypoxic tumors.

Laboratory blood parameters and machine learning for the prognosis of esophageal squamous cell carcinoma.

Background: In contemporary study, the death of esophageal squamous cell carcinoma (ESCC) patients need precise and expedient prognostic methodologies. Objective: To develop and validate a prognostic model tailored to ESCC patients, leveraging the power of machine learning (ML) techniques and drawing insights from comprehensive datasets of laboratory-derived blood parameters. Methods: Three ML approaches, including Gradient Boosting Machine (GBM), Random Survival Forest (RSF), and the classical Cox method, were employed to develop models on a dataset of 2521 ESCC patients with 27 features. The models were evaluated by concordance index (C-index) and time receiver operating characteristics (Time ROC) curves. We used the optimal model to evaluate the correlation between features and prognosis and divide patients into low- and high-risk groups by risk stratification. Its performance was analyzed by Kaplan-Meier curve and the comparison with AJCC8 stage. We further evaluate the comprehensive effectiveness of the model in ESCC subgroup by risk score and KDE (kernel density estimation) plotting. Results: RSF's C-index (0.746) and AUC (three-year AUC 0.761, five-year AUC 0.771) had slight advantage over GBM and the classical Cox method. Subsequently, 14 features such as N stage, T stage, surgical margin, tumor length, age, Dissected LN number, MCH, Na, FIB, DBIL, CL, treatment, vascular invasion, and tumor grade were selected to build the model. Based on these, we found significant difference for survival rate between low-(3-year OS 81.8%, 5-year OS 69.8%) and high-risk (3-year OS 25.1%, 5-year OS 11.5%) patients in training set, which was also verified in test set (all P < 0.0001). Compared with the AJCC8th stage system, it showed a greater discriminative ability which is also in good agreement with its staging ability. Conclusion: We developed an ESCC prognostic model with good performance by clinical features and laboratory blood parameters.

Appearance-based Gaze Estimation with Deep Learning: A Review and Benchmark.

Human gaze provides valuable information on human focus and intentions, making it a crucial area of research. Recently, deep learning has revolutionized appearance-based gaze estimation. However, due to the unique features of gaze estimation research, such as the unfair comparison between 2D gaze positions and 3D gaze vectors and the different pre-processing and post-processing methods, there is a lack of a definitive guideline for developing deep learning-based gaze estimation algorithms. In this paper, we present a systematic review of the appearance-based gaze estimation methods using deep learning. Firstly, we survey the existing gaze estimation algorithms along the typical gaze estimation pipeline: deep feature extraction, deep learning model design, personal calibration and platforms. Secondly, to fairly compare the performance of different approaches, we summarize the data pre-processing and post-processing methods, including face/eye detection, data rectification, 2D/3D gaze conversion and gaze origin conversion. Finally, we set up a comprehensive benchmark for deep learning-based gaze estimation. We characterize all the public datasets and provide the source code of typical gaze estimation algorithms. This paper serves not only as a reference to develop deep learning-based gaze estimation methods, but also a guideline for future gaze estimation research. The project web page can be found at https://phi-ai.buaa.edu.cn/Gazehub/.

Association between visceral adiposity index and risk of diabetes and prediabetes: Results from the NHANES (1999-2018).

OBJECTIVE: To investigate the association between the visceral adiposity index and the prevalence of diabetes and prediabetes in the US adult population. METHOD: We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 for ten consecutive years, including 18745 eligible participants. The weighted multivariate logistic model and fitting curve were used to explore the correlation and dose-response relationship between visceral adiposity index (VAI) and diabetes (DM) and prediabetes in the general population and the prevalence of different subgroups. RESULTS: In the fully adjusted continuous model, the risk of diabetes and prediabetes in the general population increased 0.15 times [1.15 (1.10,1.20), p<0.0001] with every increase of 1 unit of VAI. In the fully adjusted classification model, with the lowest quartile array Q1 of VAI as the reference group, Q2 of the second Quantile group, Q3 of the third Quantile group, and Q4 of the Quartile group increased 0.26 times [1.26 (1.10,1.44), p<0.001], 0.65 times [1.65 (1.43,1.89), p<0.0001], 1.60 times [2.60 (2.28,2.97), p<0.0001] respectively with the risk of diabetes and prediabetes. The above results showed that VAI was positively associated with the prevalence of diabetes and prediabetes, and the fitted curves showed a non-linear trend. (P for non-linear = 0<0.05). The results of the subgroup population were consistent with the total population and a significant interaction was found in gender (P for interaction<0.0001). CONCLUSION: In conclusion, we found a non-linear positive association between VAI and the risk of diabetes and prediabetes in the US adult population and found that women have a higher risk of diabetes and prediabetes than men; therefore, we should focus on the female population, and we call for the use of VAI to manage the development of diabetes and prediabetes in the clinical setting.

Spurious High Platelet Count without PLT Flag(S) in a Patient with Severe Aplastic Anaemia.

BACKGROUND: Platelet (PLT) count is one of the most important parameters of automated hematology, as spurious PLT reports could affect medical judgement and bring significant risks. In most cases, spurious PLT will not be reported for review criteria, which will be triggered by abnormal PLT histograms and PLT flag(s). Here, we present a case of severe aplastic anemia after hematopoietic stem cell transplantation with spurious high platelet count with normal histogram and no PLT flag(s). METHODS: The electrical impedance channel (PLT-I) and the fluorescence channel (PLT-F) of Sysmex XN-series hematology analyzer was used to obtain PLT results. Then, the sample was retested by another hematology analyzer MINDRAY BC-7500 [NR] CRP, and incubation was performed to rule out cryoglobulin interference. Furthermore, a microscope was used to estimate the PLT count by the ratio of platelets to red blood cells and observe the morphology of cells. RESULTS: Both PLT-I and PLT-F test results were spuriously high, and microscopically assessed platelet counts were relatively reliable. The observed spiny cells and ghost cells caused by hemolysis may have contributed to the inaccuracy of instrumental counting in this case. CONCLUSIONS: For special hematologic patients, PLT-I with flags may not be sufficient for screening purposes and PLT-F is not always accurate. Multiple testing methods including manual microscopy are needed.

Challenges and opportunities in obesity: the role of adipocytes during tissue fibrosis.

Obesity is a chronic disease that affects the energy balance of the whole body. In addition to increasing fat mass, tissue fibrosis occurred in white adipose tissue in obese condition. Fibrosis is the over-activation of fibroblasts leading to excessive accumulation of extracellular matrix, which could be caused by various factors, including the status of adipocytes. The morphology of adipocytes responds rapidly and dynamically to nutrient fluctuations. Adaptive hypertrophy of normal adipocytes protects peripheral organs from damage from lipotoxicity. However, the biological behavior of hypertrophic adipocytes in chronic obesity is abnormally altered. Adipocytes lead to fibrotic remodeling of the extracellular matrix by inducing unresolved chronic inflammation, persistent hypoxia, and increasing myofibroblast numbers. Moreover, adipocyte-induced fibrosis not only restricts the flexible expansion and contraction of adipose tissue but also initiates the development of various diseases through cellular autonomic and paracrine effects. Regarding anti-fibrotic therapy, dysregulated intracellular signaling and epigenetic changes represent potential candidate targets. Thus, modulation of adipocytes may provide potential therapeutic avenues for reversing pathological fibrosis in adipose tissue and achieving the anti-obesity purpose.

Combining High-Density Fat and Condensed Low-Density Fat Injections for Precise Facial Rejuvenation.

BACKGROUND: Facial aging involves ptosis, adipose atrophy, and skeletal resorption. Depletion of adipose tissue primarily affects the deep facial fat compartment, leading to facial depression or ptosis, accompanied by atrophy of the superficial compartment. Restoring volume in the deep fat compartment is crucial for facial rejuvenation, while enhancing its supportive properties is also important. The superficial fat compartment contains small-sized adipocytes, and autologous fat grafting is a popular approach. However, variability in fat retention, homogeneity, and processing methods can impact outcomes, necessitating careful selection of a suitable fat processing material for precise facial fat grafting. METHOD: A retrospective study was conducted on 50 patients who underwent facial augmentation using combined transplantation of high-density fat (HDF) and condensed low-density fat (CLDF) and 25 patients who underwent conventional Coleman fat grafting. Coleman fat was harvested by standard technique and the adipose tissue was divided into HDF and CLDF fractions through centrifugation. Subsequently, the low-density fat fraction was subjected to a process involving physical disruption followed by additional centrifugation to obtain CLDF. The CLDF fraction was consequently injected into the pre-SMAS subcutaneous layer of the superficial fat compartments. Patient satisfaction was evaluated using a typical Likert scale. Photographs were taken and imageological examinations were performed before and after treatment. RESULT: The CLDF+HDF grafting group demonstrated a significantly shorter duration of swelling (6.0 ± 1.2 to 12.6 ± 3.3 days) and higher level of patient satisfaction when compared to the Coleman fat group. No serious complications were observed among all the patients who received the injections. CONCLUSION: The use of this new treatment approach allows for precise fat transplantation in facial regions. The use of high-concentration fat filling for deep facial layers and CLDF filling for superficial layers is a safe and effective treatment plan for facial rejuvenation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

CPhaMAS: An online platform for pharmacokinetic data analysis based on optimized parameter fitting algorithm.

BACKGROUND AND OBJECTIVE: Clinical pharmacological modeling and statistical analysis software is an essential basic tool for drug development and personalized drug therapy. The learning curve of current basic tools is steep and unfriendly to beginners. The curve is even more challenging in cases of significant individual differences or measurement errors in data, resulting in difficulties in accurately estimating pharmacokinetic parameters by existing fitting algorithms. Hence, this study aims to explore a new optimized parameter fitting algorithm that reduces the sensitivity of the model to initial values and integrate it into the CPhaMAS platform, a user-friendly online application for pharmacokinetic data analysis. METHODS: In this study, we proposed an optimized Nelder-Mead method that reinitializes simplex vertices when trapped in local solutions and integrated it into the CPhaMAS platform. The CPhaMAS, an online platform for pharmacokinetic data analysis, includes three modules: compartment model analysis, non-compartment analysis (NCA) and bioequivalence/bioavailability (BE/BA) analysis. Our proposed CPhaMAS platform was evaluated and compared with existing WinNonlin. RESULTS: The platform was easy to learn and did not require code programming. The accuracy investigation found that the optimized Nelder-Mead method of the CPhaMAS platform showed better accuracy (smaller mean relative error and higher R2) in two-compartment and extravascular administration models when the initial value was set to true and abnormal values (10 times larger or smaller than the true value) compared with the WinNonlin. The mean relative error of the NCA calculation parameters of CPhaMAS and WinNonlin was <0.0001 %. When calculating BE for conventional, high-variability and narrow-therapeutic drugs. The main statistical parameters of the parameters Cmax, AUCt, and AUCinf in CPhaMAS have a mean relative error of <0.01% compared to WinNonLin. CONCLUSIONS: In summary, CPhaMAS is a user-friendly platform with relatively accurate algorithms. It is a powerful tool for analysing pharmacokinetic data for new drug development and precision medicine.

Robust Dual-Modal Speech Keyword Spotting for XR Headsets.

While speech interaction finds widespread utility within the Extended Reality (XR) domain, conventional vocal speech keyword spotting systems continue to grapple with formidable challenges, including suboptimal performance in noisy environments, impracticality in situations requiring silence, and susceptibility to inadvertent activations when others speak nearby. These challenges, however, can potentially be surmounted through the cost-effective fusion of voice and lip movement information. Consequently, we propose a novel vocal-echoic dual-modal keyword spotting system designed for XR headsets. We devise two different modal fusion approches and conduct experiments to test the system's performance across diverse scenarios. The results show that our dual-modal system not only consistently outperforms its single-modal counterparts, demonstrating higher precision in both typical and noisy environments, but also excels in accurately identifying silent utterances. Furthermore, we have successfully applied the system in real-time demonstrations, achieving promising results. The code is available at https://github.com/caizhuojiang/VE-KWS.

Lipolysis inhibition improves the survival of fat grafts through ameliorating lipotoxicity and inflammation.

Fat grafting is a promising technique for correcting soft tissue abnormalities, but oil cyst formation and graft fibrosis frequently impede the therapeutic benefit of fat grafting. The lipolysis of released oil droplets after grafting may make the inflammation and fibrosis in the grafts worse; therefore, by regulating adipose triglyceride lipase (ATGL) via Atglistatin (ATG) and Forskolin (FSK), we investigated the impact of lipolysis on fat grafts in this study. After being removed from the mice and chopped into small pieces, the subcutaneous fat from wild-type C57BL/6J mice was placed in three different solutions for two hours: serum-free cell culture medium, culture medium+FSK (50 µM), and culture medium+ATG (100 µM). Following centrifugation to remove water and free oil droplets, 0.3 mL of the fat particles per mouse was subcutaneously injected into the back of mice. Additionally, the subcutaneous fat grafting area was immediately injected with PBS (control group), ATG (30 mg/kg), and FSK (15 mg/kg) following fat transplantation. Detailed cellular events after grafting were investigated by histological staining, real-time polymerase chain reaction, immunohistochemistry/immunofluorescent staining, and quantification. Two weeks after grafting, grafts treated with ATG showed lower expression of ATGL and decreased mRNA levels of TNFα and IL-6. In contrast, grafts treated with ATG showed elevated expression levels of IL-4 and IL-13 compared to the control grafts. In addition, fewer apoptotic cells and oil cysts were observed in ATG grafts. Meanwhile, a higher CD206+/CD68+ ratio of macrophages and more CD31+ vascular endothelial cells existed in the 2-month ATG grafts. In comparison to the control, ATG treatment improved the volume retention of grafts, and decreased graft fibrosis and oil cyst formation. By preventing oil droplet lipolysis, pharmacological suppression of ATGL shielded adipocytes from lipotoxicity following grafting. Additionally, ATG ameliorated the apoptosis and inflammation brought on by adipocyte death and oil droplet lipolysis in grafted fat. These all indicate that lipolysis inhibition improved transplanted fat survival and decreased the development of oil cysts and graft fibrosis, offering a potential postoperative pharmacological intervention for bettering fat grafting.

Characterization of merozoite-specific thrombospondin-related anonymous protein (MTRAP) in Plasmodium vivax and P. knowlesi parasites.

Plasmodium vivax, the most widespread human malaria parasite, and P. knowlesi, an emerging Plasmodium that infects humans, are the phylogenetically closest malarial species that infect humans, which may induce cross-species reactivity across most co-endemic areas in Southeast Asia. The thrombospondin-related anonymous protein (TRAP) family is indispensable for motility and host cell invasion in the growth and development of Plasmodium parasites. The merozoite-specific TRAP (MTRAP), expressed in blood-stage merozoites, is supposed to be essential for human erythrocyte invasion. We aimed to characterize MTRAPs in blood-stage P. vivax and P. knowlesi parasites and ascertain their cross-species immunoreactivity. Recombinant P. vivax and P. knowlesi MTRAPs of full-length ectodomains were expressed in a mammalian expression system. The MTRAP-specific immunoglobulin G, obtained from immune animals, was used in an immunofluorescence assay for subcellular localization and invasion inhibitory activity in blood-stage parasites was determined. The cross-species humoral immune responses were analyzed in the sera of patients with P. vivax or P. knowlesi infections. The MTRAPs of P. vivax (PvMTRAP) and P. knowlesi (PkMTRAP) were localized on the rhoptry body of merozoites in blood-stage parasites. Both anti-PvMTRAP and anti-PkMTRAP antibodies inhibited erythrocyte invasion of blood-stage P. knowlesi parasites. The humoral immune response to PvMTRAP showed high immunogenicity, longevity, and cross-species immunoreactivity with P. knowlesi. MTRAPs are promising candidates for development of vaccines and therapeutics against vivax and knowlesi malaria.