Endostatin sensitizes p53-deficient non-small-cell lung cancer to genotoxic chemotherapy by targeting DNA-dependent protein kinase catalytic subunit.

Endostatin was discovered as an endogenous angiogenesis inhibitor with broad-spectrum antitumour activities. Although clinical efficacy was observed when endostatin was combined with standard chemotherapy for non-small cell lung cancer (NSCLC), as well as other cancer types, the specific mechanisms underlying the benefit of endostatin are not completely understood. Extensive investigations suggest that endostatin is a multifunctional protein possessing more than anti-angiogenic activity. Here, we found that endostatin exerts a direct chemosensitizing effect on p53-deficient tumour cells. Concomitant treatment with endostatin and genotoxic drugs resulted in therapeutic synergy in both cellular and animal models of p53-deficient NSCLC. Mechanistically, endostatin specifically interacts with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) in tumour cells and suppresses its DNA repair activity. Using isogenic NSCLC cells with different p53 statuses, we discovered that p53-deficient tumour cells show chemoresistance to genotoxic drugs, creating a synthetic dependence on DNA-PKcs-mediated DNA repair. In this setting, endostatin exerted inhibitory effects on DNA-PKcs activity, leading to accumulation of DNA lesions and promotion of the therapeutic effect of genotoxic chemotherapy. In contrast, p53-proficient tumour cells were more sensitive to genotoxic drugs so that DNA-PKcs could be cleaved by drug-activated caspase-3, making DNA-PKcs inhibition less effective during this ongoing apoptotic process. Therefore, our data demonstrate a novel mechanism for endostatin as a DNA-PKcs suppressor, and indicate that combination therapy of endostatin with genotoxic drugs could be a promising treatment strategy for cancer patients with p53-deficient tumours. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Mapping transmission foci to eliminate malaria in the People's Republic of China, 2010-2015: a retrospective analysis.

BACKGROUND: China has initiated the National Malaria Elimination Action Plan, which aims to eliminate malaria by 2020. However, the transmission of malaria occurs sporadically or in distinct foci, which greatly hampers progress toward elimination in China and other countries. The object of this study was to foci categorization and evaluates whether the response met the requirements issued by the nation or WHO. METHODS: Residual transmissions were investigated and located with fine spatial resolution mapping from parasitological confirmed malaria cases by use of routine national surveillance data. The "1-3-7" timeframes were monitored for each focus between 2012 and 2015. Each focus was identified, and the application of appropriate measures was evaluated. RESULTS: A total of 5996 indigenous cases were recorded between 2010 and 2015; during this period, the number of cases declined by 99.1% (2010, n = 4262; 2015, n = 39). Most indigenous cases (92.5%) were reported in Anhui (n = 2326), Yunnan (n = 1373), Henan (n = 930), Hubei (n = 459), and Guizhou (n = 458). The temporal distribution showed that the indigenous malaria cases were clustered during the period of May to August. A total of 320 foci were carefully investigated and analyzed: 24 were active foci; 72, residual non-active foci; and 224 cleared-up foci. For the foci response evaluation, all the active foci were investigated within 7 days, while 80.2% of the residual non-active foci were responded within 7 days. In addition, reactive case detection (RACD) was carried out with 92.9% of the active foci and vector investigation carried out with 75%. For residual non-active foci, RACD was carried out with 83.2% and vector investigation with 78.2% of the foci. CONCLUSIONS: This study used nationwide data to categorize foci in China and evaluate the response of these areas during the control and elimination phases. Our approach stratifies future control responses by identifying those locations where the elimination of endemic transmission is needed, such as in the counties at the China-Myanmar border and in Tibet. In addition, this study will help local CDC staff to reassess their needs and responses against different types of foci during the elimination and post-elimination phases.

Receptivity to malaria in the China-Myanmar border in Yingjiang County, Yunnan Province, China.

BACKGROUND: The re-establishment of malaria has become an important public health issue in and out of China, and receptivity to this disease is key to its re-emergence. Yingjiang is one of the few counties with locally acquired malaria cases in the China-Myanmar border in China. This study aimed to understand receptivity to malaria in Yingjiang County, China, from June to October 2016. METHODS: Light-traps were employed to capture the mosquitoes in 17 villages in eight towns which were categorized into four elevation levels: level 1, 0-599 m; level 2, 600-1199 m; level 3, 1200-1799 m; and level 4, > 1800 m. Species richness, diversity, dominance and evenness were used to picture the community structure. Similarity in species composition was compared between different elevation levels. Data of seasonal abundance of mosquitoes, human biting rate, density of light-trap-captured adult mosquitoes and larvae, parous rate, and height distribution (density) of Anopheles minimus and Anopheles sinensis were collected in two towns (Na Bang and Ping Yuan) each month from June to October, 2016. RESULTS: Over the study period, 10,053 Anopheles mosquitoes were collected from the eight towns, and 15 Anopheles species were identified, the most-common of which were An. sinensis (75.4%), Anopheles kunmingensis (15.6%), and An. minimus (3.5%). Anopheles minimus was the major malaria vector in low-elevation areas (< 600 m, i.e., Na Bang town), and An. sinensis in medium-elevation areas (600-1200 m, i.e., Ping Yuan town). In Na Bang, the peak human-biting rate of An. minimus at the inner and outer sites of the village occurred in June and August 2016, with 5/bait/night and 15/bait/night, respectively. In Ping Yuan, the peak human-biting rate of An. sinensis was in August, with 9/bait/night at the inner site and 21/bait/night at the outer site. The two towns exhibited seasonal abundance with high density of the two adult vectors: The peak density of An. minimus was in June and that of An. sinensis was in August. Meanwhile, the peak larval density of An. minimus was in July, but that of An. sinensis decreased during the investigation season; the slightly acidic water suited the growth of these vectors. The parous rates of An. sinensis and An. minimus were 90.46 and 93.33%, respectively. CONCLUSIONS: The Anopheles community was spread across different elevation levels. Its structure was complex and stable during the entire epidemic season in low-elevation areas at the border. The high human-biting rates, adult and larval densities, and parous rates of the two Anopheles vectors reveal an exceedingly high receptivity to malaria in the China-Myanmar border in Yingjiang County.

Through an ITIM-independent mechanism the FcγRIIB blocks B cell activation by disrupting the colocalized microclustering of the B cell receptor and CD19.

B cell activation is regulated through the interplay of the BCR with the inhibitory coreceptor FcγRIIB and the activating coreceptor CD19. Recent studies suggest that Ag-driven BCR microclusters are efficiently converted to a signaling active state on colocalization with CD19 microclusters. Using total internal reflection fluorescence microscopy-based, high-resolution, high-speed live-cell and molecule imaging approaches, we show that when co-ligated to the BCR, the FcγRIIB can inhibit B cell activation by blocking the colocalization of BCR and CD19 microclusters within the B cell immunological synapse. Remarkably, this inhibitory function of FcγRIIB is dependent not on its well-characterized ITIM-containing cytoplasmic domain, but its transmembrane domain. Indeed, human primary B cells from systemic lupus erythematosus patients homozygous for gene encoding the loss-of-function transmembrane domain mutant FcγRIIB-I232T fail to block the synaptic colocalization of the BCR with CD19, leading to dysregulated recruitment of downstream signaling molecule p-PI3K to membrane proximal signalosome. This inhibitory function of FcγRIIB in impairing the spatial-temporal colocalization of BCR and CD19 microclusters in the B cell immunological synapse may help explain the hyper-reactive features of systemic lupus erythematosus patient B cells in reported studies. These observations may also provide new targets for therapies for systemic autoimmune disease.

[Malaria Situation in the People's Republic of China in 2015].

The 2015 malaria epidemiological data reported through the annual malaria statistics reporting system were collected and analyzed. Totally 3 288 malaria cases were reported in 664 counties of 31 Provinces/Municipalities/Autonomous Regions （P/M/A） in 2015, which increased by 6.8% in comparison to that of 2014 （3 078 cases）, and the incidence in 2015 was 0.024 0/10 000. The cases were reported primarily from Provinces of Yunnan （18.4%, 606/3 288）, Jiangsu （12.3%, 405/3 288）, Sichuan （8.8%, 290/3 288）, Guangxi （7.2%, 236/3 288） and Shandong（6.4%, 212/3 288）. Of all the cases, 40（1.2%, 40/3 288） were indigenous cases, mainly distributed in the border area of Yunnan （six counties）, Tibet （one county）, Liaoning （one county） and Hainan （one county）. There was one case of whom the source of infection was unknown. The locally-infected falciparum malaria was only found in Cangyuan County of Yunnan（1 case）. The prevalence of indigenous malaria in Motuo County of the Tibet Autonomous Region was over 1/10 000. Meanwhile, there were 3 248（98.8%, 3 248/3 288） abroad-imported cases which widely distributed in the 31 P/M/As. In addition, 3 265（99.3%, 3 265/3 288） of the reported cases were confirmed in reference laboratories, comprising 878 cases of Plasmodium vivax（26.9%, 878/3 265） 1 992 cases of P. falciparum（61.0%, 1 992/3 265）, 76 cases of P. malariae（2.3%, 76/3 265）, 272 cases of P. ovale（8.3%, 272/3 265） and 47 cases of mixed infection（1.4%, 47/3 265）. Furthermore, 163 cases（5.0%, 163/3 288） with severe clinical symptoms were reported in 14 P/M/As, with 20 deaths（0.6%, 20/3 288） in 10 P/M/As. Totally 3 116 malaria cases were reported through the China Information System for Disease Control and Prevention, including 39 indigenous cases. These data reflect achievements in malaria elimination, despite that challenges remain in boarder areas of Yunnan Province and in Motuo County of the Tibet Autonomous Region. Efforts are still needed in risk assesment for malaria re-transmission.

B cell activation is regulated by the stiffness properties of the substrate presenting the antigens.

B lymphocytes are activated upon Ag sensing by BCRs. The substrate presenting the Ag can show different degrees of stiffness. It is not clear whether B cells can respond to changes in substrate stiffness. In this study we use high-resolution, high-speed live cell imaging techniques to capture the molecular events in B cell activation after the recognition of Ags tethered to polyacrylamide gel substrates with variable degrees of stiffness as quantified by Young's modulus (2.6-22.1 kPa). We show that the initiation of B cell activation is extremely sensitive to substrate stiffness. B cells exhibit much stronger activation responses when encountering Ags tethered to substrates with a high degree of stiffness as measured by the accumulation of BCR, phospho-spleen tyrosine kinase, and phosphotyrosine molecules into the B cell immunological synapse. Ags tethered to stiff substrates induce the formation of more prominent BCR and phospho-spleen tyrosine kinase microclusters with significantly enhanced colocalization as compared with Ags tethered to soft substrates. Moreover, the expression of the B cell activation marker CD69 is enhanced in B cells encountering Ags on stiffer substrates. Through time-lapse live cell imaging, we find that the different responses of B cells to substrate stiffness are only demonstrated 5 min after BCR and Ag recognition. Using a series of cytoskeleton inhibitors, we determine that the mechanosensing ability of B cells is dependent on microtubules, and only mildly linked to the actin cytoskeleton. These results suggest the importance of the mechanical properties mediated by substrate stiffness in B cell activation.

[Screening Radius of Active Case Detection and the Malaria Parasite Rate of Carriers in China-Myanmar Border].

OBJECTIVE: To explore the effective screening radii of active case detection of the 1-3-7 surveillance and response strategy, and investigate the malaria parasite rate of carriers in China-Myanmar border. METHODS: Three villages with indigenous malaria cases in Yingjiang County of Yunan Province were selected as study sites. The persons lived around the indigenous cases (index case) within the radius of 100 m, 300 m, 500 m, and 1 km were screened by microscopy and nested PCR. Parasite rate of asymptomatic carriers at different radii were calculated. RESULTS: Among 278 blood samples, the parasite rate of asymptomatic carriers was 1.1% (3/278) and 2.2% (6/278) using microscopy and nested PCR, respectively. Based on the results of nested PCR, all the asymptomatic carriers could be detected within a 300 m radius around the index case, and with the highest proportion (66.7%) in the radius of 101-300 m. CONCLUSION: The asymptomatic carriers of malaria parasites in the China-Myanmar border area can be effectively detected within a 300 m screening radius of index case by using nested PCR.

Operational research on malaria control and elimination: a review of projects published between 2008 and 2013.

A literature review for operational research on malaria control and elimination was conducted using the term 'malaria' and the definition of operational research (OR). A total of 15 886 articles related to malaria were searched between January 2008 and June 2013. Of these, 582 (3.7%) met the definition of operational research. These OR projects had been carried out in 83 different countries. Most OR studies (77%) were implemented in Africa south of the Sahara. Only 5 (1%) of the OR studies were implemented in countries in the pre-elimination or elimination phase. The vast majority of OR projects (92%) were led by international or local research institutions, while projects led by National Malaria Control Programmes (NMCP) accounted for 7.8%. With regards to the topic under investigation, the largest percentage of papers was related to vector control (25%), followed by epidemiology/transmission (16.5%) and treatment (16.3%). Only 19 (3.8%) of the OR projects were related to malaria surveillance. Strengthening the capacity of NMCPs to conduct operational research and publish its findings, and improving linkages between NMCPs and research institutes may aid progress towards malaria elimination and eventual eradication world-wide.

[Methods of detecting asymptomatic plasmodium parasites carriers].

More attention has increasingly been given to asymptomatic carriers of plasmodium parasites as a source of infection in malaria elimination settings. However, asymptomatic infections can hardly be detected by microscopy and rapid diagnostic tests (RDTs) because of no symptoms and low parasitemia. This review summarizes the evolution of methods or tests which are currently used in the field.

[Risk assessment for malaria elimination in P. R. China].

OBJECTIVE: To identify the risk area in China during the malaria elimination process, and provide the evidence for promotion of the national malaria elimination programme and implementation of elimination strategy. METHODS: Data collection was conducted in 24 endemic provinces in 2010, including data of transmission capacity, potential risk of malaria transmission and the capacity of health professional team at county level. Quantitative assessment of the malaria transmission risk as well as the capacity of health facilities were conducted based on the calculation of malaria transmission risk index (MTI) and health facilities capacity index (CI). ArcGIS 10.0 was used to develop the risk map based on the outcome of quantitative assessment. RESULTS: The data of transmission capacity, potential risk of transmission and the capacity of health professional team were collected from 2147 counties in 24 provinces. Based on MTI and CI calculated for each county, statistic results showed that about 40% of the counties were under the average level of both MTI and CI. The relationship among potential risk of transmission, the capacity of health professional team and malaria incidence were analyzed in three dimensions, and four types were categorized among 2147 counties. Type I (super-high risk area) counties (20) distributed in Yunnan (9), Guangxi (5), Henan (1), Hunan (1), Hebei (1), Sichuan (1), Chongqing (1), and Tibet (1). 17 counties were classified into type II (high risk area) area, distributed in Yunnan (3), Guangxi (2), Guizhou (2), Shaanxi (2), Guangdong (1), Jiangxi (1), Hubei (1), Sichuan (1), Gansu (1), Hebei (1), Fujian (1) and Tibet (1). A total of 170 type III (moderate risk area) counties distributed in 19 provinces including Yunnan (15), Guizhou (14), Hebei (14), Sichuan (13), Shanxi (10), Guangxi (9), Hunan (9), Anhui (9), Jiangsu (9), Shaanxi (9), Shandong (9), Chongqing (8), Gansu (8), Jiangxi (7), Henan (7), Fujian (6), Guangdong (5), Hubei (5), and Zhejiang (4). 1940 type IV (low risk area) counties distributed in 24 provinces. CONCLUSION: The distribution of four types of risk area for malaria elimination is identified in China.

Protocol to establish patient-derived xenograft and organoid for radiosensitivity of esophageal squamous cell carcinoma.

Patient-derived xenograft (PDX) and organoids derived from PDX (PDXOs) are ideal pre-clinical models, which recapitulate the tumor heterogeneity. We provide the steps to establish PDX and PDXOs from patients with esophageal squamous cell carcinoma (ESCC) and their utility in examining radiotherapy. We describe steps for generating ESCC-PDXs, four cycles of ionizing radiation treatments using X-ray on PDX, and evaluating radiosensitivity of PDXs. We then detail procedures for establishing and characterizing radioresistant organoids derived from PDX. For complete details on the use and execution of this protocol, please refer to Liu et al.,1 Yang et al.,2 and Chen et al.3.

Protocol for the generation, characterization, and functional assays of organoid cultures from normal and cancer-prone human esophageal tissues.

Multiple sampling strategies to cover different or dynamic stages of malignant continuum with organoid cultures provide a valuable platform for epithelium homeostasis, transformation, and cancer progression. Here, we present a protocol to initiate, culture, passage, and characterize organoids from normal and cancer-prone human esophageal tissues. We describe steps for multiple sampling of malignant continuum and the initiation and maintenance of multi-stage organoids. We then detail procedures for the histological characterization of organoids and co-culture systems based on organoids and stromal cells. For complete details on the use and execution of this protocol, please refer to Chen et al.1.

Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets.

Tumorigenesis is a multistep process, with oncogenic mutations in a normal cell conferring clonal advantage as the initial event. However, despite pervasive somatic mutations and clonal expansion in normal tissues, their transformation into cancer remains a rare event, indicating the presence of additional driver events for progression to an irreversible, highly heterogeneous, and invasive lesion. Recently, researchers are emphasizing the mechanisms of environmental tumor risk factors and epigenetic alterations that are profoundly influencing early clonal expansion and malignant evolution, independently of inducing mutations. Additionally, clonal evolution in tumorigenesis reflects a multifaceted interplay between cell-intrinsic identities and various cell-extrinsic factors that exert selective pressures to either restrain uncontrolled proliferation or allow specific clones to progress into tumors. However, the mechanisms by which driver events induce both intrinsic cellular competency and remodel environmental stress to facilitate malignant transformation are not fully understood. In this review, we summarize the genetic, epigenetic, and external driver events, and their effects on the co-evolution of the transformed cells and their ecosystem during tumor initiation and early malignant evolution. A deeper understanding of the earliest molecular events holds promise for translational applications, predicting individuals at high-risk of tumor and developing strategies to intercept malignant transformation.

Polymorphism in the Hsa-miR-4274 seed region influences the expression of PEX5 and enhances radiotherapy resistance in colorectal cancer.

Identifying biomarkers for predicting radiotherapy efficacy is crucial for optimizing personalized treatments. We previously reported that rs1553867776 in the miR-4274 seed region can predict survival in patients with rectal cancer receiving postoperative chemoradiation therapy. Hence, to investigate the molecular mechanism of the genetic variation and its impact on the radiosensitivity of colorectal cancer (CRC), in this study, bioinformatics analysis is combined with functional experiments to confirm peroxisomal biogenesis factor 5 (PEX5) as a direct target of miR-4274. The miR-4274 rs1553867776 variant influences the binding of miR-4274 and PEX5 mRNA, which subsequently regulates PEX5 protein expression. The interaction between PEX5 and Ku70 was verified by co-immunoprecipitation and immunofluorescence. A xenograft tumor model was established to validate the effects of miR-4274 and PEX5 on CRC progression and radiosensitivity in vivo. The overexpression of PEX5 enhances radiosensitivity by preventing Ku70 from entering the nucleus and reducing the repair of ionizing radiation (IR)-induced DNA damage by the Ku70/Ku80 complex in the nucleus. In addition, the enhanced expression of PEX5 is associated with increased IR-induced ferroptosis. Thus, targeting this mechanism might effectively increase the radiosensitivity of CRC. These findings offer novel insights into the mechanism of cancer radioresistance and have important implications for clinical radiotherapy.

Alarmin S100A8 imparts chemoresistance of esophageal cancer by reprogramming cancer-associated fibroblasts.

Chemotherapy remains the first-line treatment for advanced esophageal cancer. However, durable benefits are achieved by only a limited subset of individuals due to the elusive chemoresistance. Here, we utilize patient-derived xenografts (PDXs) from esophageal squamous-cell carcinoma to investigate chemoresistance mechanisms in preclinical settings. We observe that activated cancer-associated fibroblasts (CAFs) are enriched in the tumor microenvironment of PDXs resistant to chemotherapy. Mechanistically, we reveal that cancer-cell-derived S100A8 triggers the intracellular RhoA-ROCK-MLC2-MRTF-A pathway by binding to the CD147 receptor of CAFs, inducing CAF polarization and leading to chemoresistance. Therapeutically, we demonstrate that blocking the S100A8-CD147 pathway can improve chemotherapy efficiency. Prognostically, we found the S100A8 levels in peripheral blood can serve as an indicator of chemotherapy responsiveness. Collectively, our study offers a comprehensive understanding of the molecular mechanisms underlying chemoresistance in esophageal cancer and highlights the potential value of S100A8 in the clinical management of esophageal cancer.

Maximizing the Value of Real-World Data and Real-World Evidence to Accelerate Healthcare Transformation in China: Summary of External Advisory Committee Meetings.

Use of real-world data (RWD) is gaining wide attention. To bridge the gap between diverse healthcare stakeholders and to leverage the impact of Chinese real-world evidence (RWE) globally, a multi-stakeholder External Advisory Committee (EAC) and EAC meetings were initiated, aiming to elucidate the current and evolving RWD landscape in China, articulate the values of RWE in ensuring Chinese patients' equitable access to affordable medicines and solutions, and identify strategic opportunities and partnerships for expansion of RWE generation in China. Chinese and international experts who are clinicians and academic researchers were selected as EAC members based on their professional background and familiarity with RWD/RWE. Three EAC meetings were held quarterly in 2023. Various topics were presented and discussed for insights and suggestions. Nine experts from China, one from South Korea, and two from Europe were selected as EAC members and attended these meetings. Experts' presentations were summarized by theme, including the RWD landscape and RWE enablement in China, as well as global development of a patient-centric ecosystem. Experts' insights and suggestions on maximizing the RWD/RWE value to accelerate healthcare transformation in China were collected. We concluded that though data access, sharing, and quality are still challenging, RWD is developing to support evidence generation in the medicinal product lifecycle, inform clinical practice, and empower patient management in China. RWD/RWE creates value, accelerates healthcare transformation, and improves patient outcomes. Fostering a patient-centric ecosystem across healthcare stakeholders and maintaining global partnerships and collaboration are essential for unlocking the power of RWD/RWE.

Multiomics and blood-based biomarkers of moyamoya disease: protocol of Moyamoya Omics Atlas (MOYAOMICS).

BACKGROUND: Moyamoya disease (MMD) is a rare and complex cerebrovascular disorder characterized by the progressive narrowing of the internal carotid arteries and the formation of compensatory collateral vessels. The etiology of MMD remains enigmatic, making diagnosis and management challenging. The MOYAOMICS project was initiated to investigate the molecular underpinnings of MMD and explore potential diagnostic and therapeutic strategies. METHODS: The MOYAOMICS project employs a multidisciplinary approach, integrating various omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, to comprehensively examine the molecular signatures associated with MMD pathogenesis. Additionally, we will investigate the potential influence of gut microbiota and brain-gut peptides on MMD development, assessing their suitability as targets for therapeutic strategies and dietary interventions. Radiomics, a specialized field in medical imaging, is utilized to analyze neuroimaging data for early detection and characterization of MMD-related brain changes. Deep learning algorithms are employed to differentiate MMD from other conditions, automating the diagnostic process. We also employ single-cellomics and mass cytometry to precisely study cellular heterogeneity in peripheral blood samples from MMD patients. CONCLUSIONS: The MOYAOMICS project represents a significant step toward comprehending MMD's molecular underpinnings. This multidisciplinary approach has the potential to revolutionize early diagnosis, patient stratification, and the development of targeted therapies for MMD. The identification of blood-based biomarkers and the integration of multiple omics data are critical for improving the clinical management of MMD and enhancing patient outcomes for this complex disease.

[Analysis report of the national technique competition for diagnosis of parasitic diseases in 2012: I. Capability analysis of Plasmodium detection].

OBJECTIVE: To analyze the result of the national technique competition for diagnosis of parasitic diseases in 2012, so as to understand the capability of detection on Plasmodium parasites among professionals from institutes for disease control and prevention at different levels. METHODS: Four professionals from institution were selected as contestants (age < or = 45 and at least two contestants from county-level institution). The content of the competition included making thick and thin blood slides of Plasmodium (3 slides in 30 min, 10 scores as full marks and 6 as passing score) and identification of species and number with microscopy (5 slides, 8 min per slide, 30 scores as full marks and 18 as passing score). All contestants were grouped by gender, age, professional title, level of institution, classification according to malaria endemicity, geographical location and economic development of the province. Their scores were statistically analyzed by SPSS 16.0 software. RESULTS: The average score of blood smear making test in 120 contestants from 30 provinces was 8.7, the highest was 10 and the lowest was 5.8, 118 (98.3%) contestants passed the test. The average score of blood smear reading was 16.0, the highest was 29 and the lowest was 0, 52 (43.3%) contestants passed the test. There were no significant differences for the scores among genders, ages (< or = 30, 31-40, > 40), professional titles (junior, intermediate and senior), institution levels (provincial, municipal or county level) (P > 0.05). However, there was a significant difference among provinces with different malaria endemicity, geographical location and development status (P < 0.05). For the blood slide-making and film-reading, scores of contestants from malaria endemic provinces including Class I (9.29 +/- 0.41, 18.17 +/- 6.42), Class II (8.92 +/- 0.79, 18.31 +/- 6.94) and Class III (8.61 +/- 0.89, 15.63 +/- 7.52) were higher than those from non-endemic provinces (7.95 +/- 1.00, 10.19 +/- 7.01) (P < 0.01). Scores of contestants from southern provinces (9.16 +/- 0.61, 18.82 +/- 6.78) were significantly higher than that from northern ones (8.30 +/- 0.99, 13.23 +/- 7.45) (P < 0.01). The film-reading scores were significantly higher in those from eastern provinces (18.20 +/- 6.88) than those from western (13.39 +/- 7.60) (P < 0.05), while no significant difference was found in blood slide-making (P > 0.05). CONCLUSION: The capability of malaria parasite detection is imbalanced.

Corrigendum: Development and validation of a model for predicting the risk of brain arteriovenous malformation rupture based on three-dimensional morphological features.

[This corrects the article DOI: 10.3389/fneur.2022.979014.].

Albumosomes formed by cytoplasmic pre-folding albumin maintain mitochondrial homeostasis and inhibit nonalcoholic fatty liver disease.

Hepatic mitochondrial dysfunction contributes to the progression of nonalcoholic fatty liver disease (NAFLD). However, the factors that maintain mitochondrial homeostasis, especially in hepatocytes, are largely unknown. Hepatocytes synthesize various high-level plasma proteins, among which albumin is most abundant. In this study, we found that pre-folding albumin in the cytoplasm is completely different from folded albumin in the serum. Mechanistically, endogenous pre-folding albumin undergoes phase transition in the cytoplasm to form a shell-like spherical structure, which we call the "albumosome". Albumosomes interact with and trap pre-folding carnitine palmitoyltransferase 2 (CPT2) in the cytoplasm. Albumosomes control the excessive sorting of CPT2 to the mitochondria under high-fat-diet-induced stress conditions; in this way, albumosomes maintain mitochondrial homeostasis from exhaustion. Physiologically, albumosomes accumulate in hepatocytes during murine aging and protect the livers of aged mice from mitochondrial damage and fat deposition. Morphologically, mature albumosomes have a mean diameter of 4µm and are surrounded by heat shock protein Hsp90 and Hsp70 family proteins, forming a larger shell. The Hsp90 inhibitor 17-AAG promotes hepatic albumosomal accumulation in vitro and in vivo, through which suppressing the progression of NAFLD in mice.