YTHDC1 as a tumor progression suppressor through modulating FSP1-dependent ferroptosis suppression in lung cancer.

Ferroptosis is a regulated cell death process initiated by iron-dependent phospholipid peroxidation and is mainly suppressed by GPX4-dependent and FSP1-dependent surveillance mechanisms. However, how the ferroptosis surveillance system is regulated during cancer development remains largely unknown. Here, we report that the YTHDC1-mediated m6A epigenetic regulation of FSP1 alleviates the FSP1-dependent ferroptosis suppression that partially contributes to the tumor suppressive role of YTHDC1 in lung cancer progression. YTHDC1 knockdown promoted the lung tumor progression and upregulated FSP1 protein level that resulted in ferroptosis resistance of lung cancer cells. Silencing FSP1 abrogated YTHDC1 knockdown-induced proliferation increase and ferroptosis resistance. Mechanistically, YTHDC1 binding to the m6A sites in the FSP1 3'-UTR recruited the alternative polyadenylation regulator CSTF3 to generate a less stable shorter 3'-UTR contained FSP1 mRNA, whereas YTHDC1 downregulation generated the longer 3'-UTR contained FSP1 mRNA that is stabilized by RNA binding protein HuR and thus led to the enhanced FSP1 protein level. Therefore, our findings identify YTHDC1 as a tumor progression suppressor in lung cancer and a ferroptosis regulator through modulating the FSP1 mRNA stability and thus suggest a ferroptosis-related therapeutic option for YTHDC1high lung cancer.

Downregulation of N6-methyladenosine-modified LINC00641 promotes EMT, but provides a ferroptotic vulnerability in lung cancer.

The prognosis of lung cancer is poor with few effective therapies. Targeting ferroptosis is a new promising strategy for cancer therapy. LINC00641 has been involved in several cancers, however, its specific roles in lung cancer treatment remain largely unknown. Here, we reported that LINC00641 was down-regulated in tumor tissues and its downregulation was associated with poor outcomes in lung adenocarcinoma. LINC00641 was localized primarily in the nucleus and was modified by m6A. The nuclear m6A reader YTHDC1 regulated LINC00641 expression by affecting its stability. We demonstrated that LINC00641 suppressed lung cancer by inhibiting migration and invasion in vitro and metastasis in vivo. Knockdown of LINC00641 upregulated HuR protein level (especially in the cytoplasm), which subsequently increased N-cadherin levels by stabilizing its mRNA, then ultimately promoted EMT. Interestingly, LINC00641 knockdown in lung cancer cells increased the arachidonic acid metabolism and promoted ferroptosis sensitivity. Our findings identified LINC00641 as a tumor suppressor through inhibiting EMT. In another aspect, low expression of LINC00641 caused a ferroptotic vulnerability in lung cancer cells, which may serve as a potential ferroptosis-related therapeutic target for lung cancer.

Study of an Ultrasensitive Label-Free Electrochemiluminescent Immunosensor Fabricated with a Composite Electrode for Detecting the Glutamate Decarboxylase Antibody.

Antibody testing for the glutamic acid decarboxylase 65 antibody (GADA) is widely used as a golden standard for autoimmune diabetes diagnosis, while current methods for antibody testing are not sensitive enough for clinical usage. Here, a label-free electrochemiluminescent (ECL) immunosensor for detecting GADA in autoimmune diabetes is fabricated and investigated. In the designed immunosensor, a composite film including the multiwalled carbon nanotubes (MWCNTs), zinc oxide (ZnO), and Au nanoparticles (AuNPs) was prepared through nanofabrication processes to improve the performance of sensor. The MWCNTs, which can provide a larger specific surface area, ZnO as a good photocatalytic material, and AuNPs that can enhance the ECL signal of luminol and immobilize the GAD65 antigen were applied to prefunctionalize indium tin oxide (ITO) glass based on a nanofabrication process. The GADA concentration was detected using the ECL immunosensor after incubating with GAD65 antigen-coated prefunctionalized ITO glass. After a direct immunoreaction, it is found that the degree of decreased ECL intensity has a good linear regression toward the logarithm of the GADA concentration in the range of 0.01 to 50 ng mL-1 with a detection limit down to 10 pg mL-1. Human serum samples positive or negative for GADA all nicely fell in the expected area. The fabricated immunosensor with excellent sensitivity, specificity, and stability has potential capability for clinical usage in GADA detection.

A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m6A reader YTHDC1.

SLC12A5, a neuron-specific potassium-chloride co-transporter, has been reported to promote tumor progression, however, the underlying mechanism remains unclear. Here we report that SLC12A5 functions as an oncogene to promote tumor progression and castration resistance of prostate cancer through the N6-methyladenosine (m6A) reader YTHDC1 and the transcription factor HOXB13. We have shown that the level of SLC12A5 was increased in prostate cancer, in comparison to its normal counterparts, and further elevated in castration-resistant prostate cancer (CRPC). The enhanced expression of SLC12A5 mRNA was associated with neuroendocrine prostate cancer (NEPC) progression and poor survival in prostate cancer. Furthermore, we demonstrated that SLC12A5 promoted the castration resistance development of prostate cancer in addition to the cell proliferation and migration. Interestingly, SLC12A5 was detected in the cell nucleus and formed a complex with nuclear m6A reader YTHDC1, which in turn upregulated HOXB13 to promote the prostate cancer progression. Therefore, our findings reveal a mechanism that how the potassium-chloride cotransporter SLC12A5 promotes the tumor progression and provide a therapeutic opportunity for prostate cancer to apply the neurological disorder drug SLC12A5 inhibitors.

The imported infections among foreign travelers in China: an observational study.

BACKGROUND: In the past few decades, globalization has rendered more frequent and intensive population movement between countries, which has changed the original disease spectrum and brought a huge health impact on the global population including China. This study aims to describe the spectrum and epidemiological characteristics of imported infections among foreign travelers travelling to China. METHODS: The data on imported infections among foreign travelers were obtained from Custom Inbound Screening System (CISS) and the National Notifiable Infectious Disease Reporting System (NNIDRS). All the infections were classified into respiratory, gastrointestinal, vector-borne, blood/sex-transmitted and mucocutaneous diseases, of which case numbers and incidences were calculated and the proportions were compared among subgroups. RESULTS: In total, 17,189 travelers diagnosed with 58 imported infectious diseases were reported from 2014 to 2018, with an overall incidence of 122.59 per million. Respiratory infection (7,351 cases, mainly influenza) and blood/sex-transmitted diseases (6,114 cases mainly Hepatitis B and HIV infection) were the most frequently diagnosed diseases, followed by vector-borne infections (3,128 cases, mainly dengue fever and malaria). The highest case number was from Asia and Europe, while the highest incidence rate was from Africa (296.00 per million). When specific diagnosis was compared, both the highest absolute case number and incidence were observed for influenza. An obvious seasonal pattern was observed for vector-borne diseases, with the annual epidemic spanning from July to November. The origin-destination matrices disclosed the movement of imported infection followed specific routes. CONCLUSIONS: Our study provided a profile of infectious diseases among foreign travelers travelling to China and pinpointed the target regions, seasons and populations for prevention and control, to attain an informed control of imported infections in China.

Recent Progress on Flexible Room-Temperature Gas Sensors Based on Metal Oxide Semiconductor.

With the rapid development of the Internet of Things, there is a great demand for portable gas sensors. Metal oxide semiconductors (MOS) are one of the most traditional and well-studied gas sensing materials and have been widely used to prepare various commercial gas sensors. However, it is limited by high operating temperature. The current research works are directed towards fabricating high-performance flexible room-temperature (FRT) gas sensors, which are effective in simplifying the structure of MOS-based sensors, reducing power consumption, and expanding the application of portable devices. This article presents the recent research progress of MOS-based FRT gas sensors in terms of sensing mechanism, performance, flexibility characteristics, and applications. This review comprehensively summarizes and discusses five types of MOS-based FRT gas sensors, including pristine MOS, noble metal nanoparticles modified MOS, organic polymers modified MOS, carbon-based materials (carbon nanotubes and graphene derivatives) modified MOS, and two-dimensional transition metal dichalcogenides materials modified MOS. The effect of light-illuminated to improve gas sensing performance is further discussed. Furthermore, the applications and future perspectives of FRT gas sensors are also discussed.

The Selective CO2 Adsorption and Photothermal Conversion Study of an Azo-Based Cobalt-MOF Material.

A new metal-organic framework (MOF), [Co2(L)2(azpy)]n (compound 1, H2L = 5-(pyridin-4-ylmethoxy)-isophthalic acid, azpy = 4,4'-azopyridine), was synthesized by a solvothermal method and further characterized by elemental analysis, IR spectra, thermogravimetric analysis, single-crystal and powder X-ray diffraction. The X-ray single-crystal diffraction analysis for compound 1 indicated that two cis L22- ligands connected to two cobalt atoms resulted in a macrocycle structure. Through a series of adsorption tests, we found that compound 1 exhibited a high capacity of CO2, and the adsorption capacity could reach 30.04 cm3/g. More interestingly, under 273 K conditions, the adsorption of CO2 was 41.33 cm3/g. In addition, when the Co-MOF was irradiated by a 730 nm laser, rapid temperature increases for compound 1 were observed (temperature variation in 169 s: 26.6 °C), showing an obvious photothermal conversion performance. The photothermal conversion efficiency reached 20.3%, which might be due to the fact that the parallel arrangement of azo units inhibited non-radiative transition and promoted photothermal conversion. The study provides an efficient strategy for designing MOFs for the adsorption of CO2 and with good photothermal conversion performance.

Decline of onset-to-diagnosis interval and its impacts on clinical outcome of COVID-19 in China: a nation-wide observational study.

BACKGROUND: To quantitatively assess the impact of the onset-to-diagnosis interval (ODI) on severity and death for coronavirus disease 2019 (COVID-19) patients. METHODS: This retrospective study was conducted based on the data on COVID-19 cases of China over the age of 40 years reported through China's National Notifiable Infectious Disease Surveillance System from February 5, 2020 to October 8, 2020. The impacts of ODI on severe rate (SR) and case fatality rate (CFR) were evaluated at individual and population levels, which was further disaggregated by sex, age and geographic origin. RESULTS: As the rapid decline of ODI from around 40 days in early January to < 3 days in early March, both CFR and SR of COVID-19 largely dropped below 5% in China. After adjusting for age, sex, and region, an effect of ODI on SR was observed with the highest OR of 2.95 (95% CI 2.37‒3.66) at Day 10-11 and attributable fraction (AF) of 29.1% (95% CI 22.2‒36.1%) at Day 8-9. However, little effect of ODI on CFR was observed. Moreover, discrepancy of effect magnitude was found, showing a greater effect from ODI on SR among patients of male sex, younger age, and those cases in Wuhan. CONCLUSION: The ODI was significantly associated with the severity of COVID-19, highlighting the importance of timely diagnosis, especially for patients who were confirmed to gain increased benefit from early diagnosis to some extent.

Investigation of stretchable strain sensor based on CNT/AgNW applied in smart wearable devices.

Stretchable strain sensor, an important paradigm of wearable sensor which can be attached onto clothing or even human skin, is widely used in healthcare, human motion monitoring and human-machine interaction. Pattern-available and facile manufacturing process for strain sensor is pursued all the time. A carbon nanotube (CNT)/silver nanowire (AgNW)-based stretchable strain sensor fabricated by a facile process is reported here. The strain sensor exhibits a considerable Gauge factor of 6.7, long-term durability (>1000 stretching cycles), fast response and recovery (420 ms and 600 ms, respectively), hence the sensor can fulfill the measurement of finger movement. Accordingly, a smart glove comprising a sensor array and a flexible printed circuit board is assembled to detect the bending movement of five fingers simultaneously. Moreover, the glove is wireless and basically fully flexible, it can detect the finger bending of wearer and display the responses distinctly on an APP of a smart phone or a host computer. Our strain senor and smart glove will broaden the materials and applications of wearable sensors.

Etiological and epidemiological features of acute meningitis or encephalitis in China: a nationwide active surveillance study.

BACKGROUND: Acute meningitis or encephalitis (AME) results from a neurological infection causing high case fatality and severe sequelae. AME lacked comprehensive surveillance in China. METHODS: Nation-wide surveillance of all-age patients with AME syndromes was conducted in 144 sentinel hospitals of 29 provinces in China. Eleven AME-causative viral and bacterial pathogens were tested with multiple diagnostic methods. FINDINGS: Between 2009 and 2018, 20,454 AME patients were recruited for tests. Based on 9,079 patients with all-four-virus tested, 28.43% (95% CI: 27.50%‒29.36%) of them had at least one virus-positive detection. Enterovirus was the most frequently determined virus in children <18 years, herpes simplex virus and Japanese encephalitis virus were the most frequently determined in 18-59 and ≥60 years age groups, respectively. Based on 6,802 patients with all-seven-bacteria tested, 4.43% (95% CI: 3.94%‒4.91%) had at least one bacteria-positive detection, Streptococcus pneumoniae and Neisseria meningitidis were the leading bacterium in children aged <5 years and 5-17 years, respectively. Staphylococcus aureus was the most frequently detected in adults aged 18-59 and ≥60 years. The pathogen spectrum also differed statistically significantly between northern and southern China. Joinpoint analysis revealed age-specific positive rates, with enterovirus, herpes simplex virus and mumps virus peaking at 3-6 years old, while Japanese encephalitis virus peaked in the ≥60 years old. As age increased, the positive rate for Streptococcus pneumoniae and Escherichia coli statistically significantly decreased, while for Staphylococcus aureus and Streptococcus suis it increased. INTERPRETATION: The current findings allow enhanced identification of the predominant AME-related pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures in China, and a possible reassessment of vaccination strategy. FUNDING: China Mega-Project on Infectious Disease Prevention and the National Natural Science Funds.

Hollow MXene Sphere-Based Flexible E-Skin for Multiplex Tactile Detection.

Skin-like electronics that can provide comprehensively tactile sensing is required for applications such as soft robotics, health monitoring, medical treatment, and human-machine interfaces. In particular, the capacity to monitor the contact parameters such as the magnitude, direction, and contact location of external forces is crucial for skin-like tactile sensing devices. Herein, a flexible electronic skin which can measure and discriminate the contact parameters in real time is designed. It is fabricated by integrating the three-dimensional (3D) hollow MXene spheres/Ag NW hybrid nanocomposite-based embedded stretchable electrodes and T-ZnOw/PDMS film-based capacitive pressure sensors. To the best of our knowledge, it is the first stretchable electrode to utilize the 3D hollow MXene spheres with the essential characteristic, which can effectively avoid the drawbacks of stress concentration and shedding of the conductive layer. The strain-resistance module and the pressure-capacitance module show the excellent sensing performance in stability and response time, respectively. Moreover, a 6 × 6 sensor array is used as a demonstration to prove that it can realize the multiplex detection of random external force stimuli without mutual interference, illustrating its potential applications in biomimetic soft wearable devices, object recognition, and robotic manipulation.

Characteristics of diarrheagenic Escherichia coli among patients with acute diarrhea in China, 2009‒2018.

Objectives To investigate the epidemiological features of diarrheagenic Escherichia coli (DEC) in patients with acute diarrhea in China. Methods An active sentinel surveillance was performed in all-age patients with acute diarrhea in China, 2009‒2018. DEC was isolated and identified by serological assay and PCR from stool samples. Results DEC was determined in 6.68% (6,119/91,651) of the patients, with higher positive rates among females than among males (6.97% vs. 6.46%) and among 18‒59 years patients (7.88%) than among other age groups. Five pathotypes were identified, the most prevalent was enteroaggregative E. coli (EAEC), followed by enteropathogenic E. coli (EPEC), and enterotoxigenic E. coli (ETEC). Pediatric patients <5 years had higher positive rate of EAEC (2.07%), followed by EPEC (1.81%), and enterohemorrhagic E. coli (EHEC) (0.31%), while the 18‒59 years patients had higher infection of ETEC (2.36%). ETEC and EPEC were more frequently identified in urban than rural areas, with age and gender adjusted positive rate of 1.68% vs. 1.14% respectively, and 1.77% vs. 1.55%, while EIEC and EHEC were more frequently identified in rural areas. Conclusions These findings highlight the epidemiology features of DEC and underscores the need for conducting DEC surveillance.

Etiological and epidemiological features of acute respiratory infections in China.

Nationwide prospective surveillance of all-age patients with acute respiratory infections was conducted in China between 2009‒2019. Here we report the etiological and epidemiological features of the 231,107 eligible patients enrolled in this analysis. Children <5 years old and school-age children have the highest viral positivity rate (46.9%) and bacterial positivity rate (30.9%). Influenza virus, respiratory syncytial virus and human rhinovirus are the three leading viral pathogens with proportions of 28.5%, 16.8% and 16.7%, and Streptococcus pneumoniae, Mycoplasma pneumoniae and Klebsiella pneumoniae are the three leading bacterial pathogens (29.9%, 18.6% and 15.8%). Negative interactions between viruses and positive interactions between viral and bacterial pathogens are common. A Join-Point analysis reveals the age-specific positivity rate and how this varied for individual pathogens. These data indicate that differential priorities for diagnosis, prevention and control should be highlighted in terms of acute respiratory tract infection patients' demography, geographic locations and season of illness in China.

Etiological, epidemiological, and clinical features of acute diarrhea in China.

National-based prospective surveillance of all-age patients with acute diarrhea was conducted in China between 2009‒2018. Here we report the etiological, epidemiological, and clinical features of the 152,792 eligible patients enrolled in this analysis. Rotavirus A and norovirus are the two leading viral pathogens detected in the patients, followed by adenovirus and astrovirus. Diarrheagenic Escherichia coli and nontyphoidal Salmonella are the two leading bacterial pathogens, followed by Shigella and Vibrio parahaemolyticus. Patients aged <5 years had higher overall positive rate of viral pathogens, while bacterial pathogens were more common in patients aged 18‒45 years. A joinpoint analysis revealed the age-specific positivity rate and how this varied for individual pathogens. Our findings fill crucial gaps of how the distributions of enteropathogens change across China in patients with diarrhea. This allows enhanced identification of the predominant diarrheal pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures.

Spider Web-like Flexible Tactile Sensor for Pressure-Strain Simultaneous Detection.

Multiparameter integrated sensors are required for the next generation of flexible wearable electronics. However, mutual interference between detected signals is a technical bottleneck for a flexible tactile sensor to realize pressure-strain monitoring simultaneously and sensitively. Herein, a flexible dual-parameter pressure-strain sensor based on the three-dimensional (3D) tubular graphene sponge (TGS) and spider web-like stretchable electrodes is designed and fabricated. As the pressure-sensitive module, the unique 3D-TGS with an uninterrupted network of tubular graphene and high graphitic degree demonstrates great robust compressibility, supporting compression to ∼20% without shape collapse. The spider web-like stretchable electrodes as the strain-sensitive module are fabricated by a spray-embedded process based on the hierarchical multiscale hybrid nanocomposite of Ag nanowires (NWs) and carbon nanotubes (CNTs) with an optimal mass ratio. By comparing the output signals of spider web-like flexible electrodes, the magnitude and direction of the applied force can be effectively monitored simultaneously. Moreover, the potential applications of the flexible dual-parameter pressure-strain device in human-machine interaction are also explored, showing great promise in artificial intelligence and wearable systems.

Epidemiology of imported infectious diseases, China, 2014-18.

BACKGROUND: The frequent movement of population between countries brings an increasing number of travel-related infections. This study aims to define the spectrum and dynamics of imported infections observed from international travel in the Chinese mainland. METHODS: Sick travellers were screened by inbound sentinel surveillance and post-travel clinic visits from 2014 to 18. The infections were classified as respiratory, gastrointestinal, vector-borne, blood/sexually transmitted and mucocutaneous. The analysed variables included the place of origin of the travellers (Chinese or foreign) and the time when travel-related infection was present (at the time of return, during travel and post-travel visits to the clinic). RESULTS: In total, 58 677 cases were identified amongst 1 409 265 253 travellers, with an incidence of 41.64/million, comprising during-travel incidence of 27.44/million and a post-travel incidence of 14.20/million. Respiratory infections constituted the highest proportion of illnesses during travel (81.19%, 31 393 of 38 667), which mainly came from Asian countries and tourists; with influenza virus and rhinovirus infections being mainly diagnosed. Vector-borne diseases constituted the highest proportion of post-travel illnesses (98.14%, 19 638 of 20 010), which were mainly diagnosed from African countries and labourers; with malaria and dengue fever being mainly diagnosed. The differential infection spectrum varied in terms of the traveller's demography, travel destination and travel purpose. As such, a higher proportion of foreign travellers had blood/sexually transmitted diseases (89.85%, 2832 of 3152), while Chinese citizens had a higher prevalence of vector-borne diseases (85.98%, 19 247 of 22 387) and gastrointestinal diseases (79.36%, 1115 of 1405). The highest incidence rate was observed amongst travellers arriving from Africa, while the lowest was observed amongst travellers arriving from Europe. CONCLUSIONS: The findings might help in preparing recommendations for travellers and also aid in primary care or other clinics that prepare travellers before trips abroad. The findings will also help to identify locations and the associated types of infections that might require attention.

Ultrahigh-Sensitive Finlike Double-Sided E-Skin for Force Direction Detection.

Flexible pressure sensing is required for the excellent sensing performance and dexterous manipulation of the measured objects in their potential applications. Particularly, the ability to measure and discriminate the direction of force, contact surface, and contact location in real time is crucial for robotics with tactile feedback. Herein, a three-dimensional elastic porous carbon nanotube (CNT) sponge is synthesized by chemical vapor deposition, which is successfully applied in the piezoresistive sensor. In situ scanning electron microscopy study intuitively illustrates the characteristics that the microfibers of the CNT sponge distort and contact with each other under an external force. As a result, new conductive paths are created at the contact points between the CNT microfibers, which provides a basic sensing principle for a piezoresistive sensor. The CNT sponge-based sensor has an ultrahigh sensitivity in a wide pressure range (0-4 kPa for 4015.8 kPa-1), a rapid response time of 120 ms, and excellent durability over 5000 cycles. Moreover, a finlike flexible double-sided electronic skin (e-skin) is fabricated by a simple method to achieve force direction detection, which has potential applications in intelligent wearable devices and human-machine interaction.

Adefovir Dipivoxil plus Chinese Medicine in HBeAg-Positive Chronic Hepatitis B Patients: A Randomized Controlled 48-Week Trial.

OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION: Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).

Endophthalmitis associated with fungal keratitis and penetrating injuries in North China.

PURPOSE: To report the laboratory findings, management strategies, and visual outcomes of culture-proven exogenous fungal endophthalmitis in North China. METHODS: The microbiological and treatment records of patients with culture-positive exogenous fungal endophthalmitis who visited the Affiliated Hospital of Qingdao University from January 2012 to December 2016 were reviewed. RESULTS: A total of 39 eyes (39 patients) were identified over a 5-year period. Exogenous fungal endophthalmitis was associated with penetrating trauma in 22 eyes (56.4%), fungal keratitis in 15 eyes (38.5%), and intraocular surgery in 2 eyes (5.1%). Hyphae were found in 29 of 37 smear samples (78.4%) by direct microscopic examination. Fungal pathogens cultured from 39 samples were identified as 10 genera and 15 species. Filamentous fungi (molds) accounted for 94.9% (37 samples), including Fusarium (19, 48.7%) and Aspergillus (11, 28.2%). Most keratitis cases were caused by Fusarium (11 of 15; 73.3 %). Aspergillus was isolated from nine penetrating ocular trauma cases (9 of 22; 40.9%). Three eyes receiving evisceration had fungal and bacteria coinfection (3 of 39, 7.7%) with Aspergillus and Bacillus. At least, one surgical intervention was performed in all 39 eyes and 28 (71.8%) eyes underwent two or more procedures, including surgeries and intraocular injections. Twenty-nine patients received intraocular antifungal therapy with amphotericin B and/or voriconazole. Visual acuity at discharge from the hospital was significantly better than the initial visual acuity (p < 0.001). Final vision of 20/400 or better was achieved in 22 (56.4%) eyes. CONCLUSIONS: This study highlighted the differences between clinical categories of exogenous fungal endophthalmitis. Trauma was the major etiological factor. Molds were the most common pathogens, with Fusarium ranking first, followed by Aspergillus. Fungal and bacterial coinfection mostly occurred after metal penetrating trauma, and Bacillus was the primary bacterial pathogen. Coinfection may be one reason of evisceration. Immediate intravitreal antifungal therapy combined with vitrectomy was effective for exogenous fungal endophthalmitis. Amphotericin B and voriconazole were commonly used antifungal agents.

lncRNA PCAT-1 interacting with FZD6 contributes to the malignancy of acute myeloid leukemia cells through activating Wnt/ß-catenin signaling pathway.

Accumulating evidence has suggested the involvement of long noncoding RNAs (lncRNAs) on the acute myeloid leukemia (AML). Therefore, this study aimed to investigate the unknown function of lncRNA Prostate cancer-associated transcript-1 (PCAT-1) in AML cells. Our data found that PCAT-1 was highly expressed in AML-M1/2 and AML-M3 patients than normal controls and its expression was significantly up-regulated in AML cell lines Kasumi-6 and HL-60. The functional experiments demonstrated that knockdown of PCAT-1 remarkably inhibited proliferation, arrested cell cycle progression and triggered apoptosis of AML cells. Mechanistically, we revealed that PCAT-1 could directly interact with FZD6 protein to regulate its stability. Overexpression of FZD6 partly abolished the effects of PCAT-1 silencing on AML cells. Our integrated experiments then suggested that PCAT-1 could activate the Wnt/ß-catenin signaling pathway in an FZD6-dependent manner. Taken together, the present study indicated that PCAT-1 interacting with FZD6 to activate Wnt/ß-catenin signaling, which may play an important role in the pathogenesis of AML.