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Abstract In recent years, illegal felling of and damage to the incense tree Aquilaria sinensis (Lour.) Spreng. have been reported in Hong Kong. Their native populations are under increasingly severe threat. Therefore, the development of a standard and efficient method to classify and document wounds on vulnerable trees is urgently needed for conservation purposes. In this study, photogrammetry was used to document wounds in A. sinensis through 3D modeling. A total of 752 wound records from 484 individual A. sinensis trees from Hong Kong were included to establish a new wound classification system. Our major findings include a novel standardized procedure for photogrammetric documentation and a wound classification system. The results of this study will facilitate A. sinensis conservation, by enhancing wound documentation and information transfer to law enforcement and education.

Abstract Basal-like breast cancers (BLBCs) are among the most aggressive cancers, partly due to their enrichment of cancer stem cells (CSCs). Breast CSCs can be generated from luminal-type cancer cells via epithelial-mesenchymal transition (EMT). GATA3 maintains luminal cell fate, and its expression is lost or reduced in BLBCs. However, deletion of Gata3 in mice or cells results in early lethality or proliferative defects. It is unknown how loss-of-function of GATA3 regulates EMT and CSCs in breast cancer. We report here that haploid loss of Gata3 in mice lacking p18Ink4c, a cell cycle inhibitor, up-regulates Fra1, an AP-1 family protein that promotes mesenchymal traits, and downregulates c-Fos, another AP-1 family protein that maintains epithelial fate, leading to activation of EMT and promotion of mammary tumor initiation and metastasis. Depletion of Gata3 in luminal tumor cells similarly regulates Fra1 and c-Fos in activation of EMT. GATA3 binds to FOSL1 (encoding FRA1) and FOS (encoding c-FOS) loci to repress FOSL1 and activate FOS transcription. Deletion of Fra1 or reconstitution of Gata3, but not reconstitution of c-Fos, in Gata3 deficient tumor cells inhibits EMT, preventing tumorigenesis and/or metastasis. In human breast cancers, GATA3 expression is negatively correlated with FRA1 and positively correlated with c-FOS. Low GATA3 and FOS, but high FOSL1, are characteristics of BLBCs. Together, these data provide the first genetic evidence indicating that loss of function of GATA3 in mammary tumor cells activates FOSL1 to promote mesenchymal traits and CSC function, while concurrently repressing FOS to lose epithelial features. We demonstrate that FRA1 is required for the activation of EMT in GATA3 deficient tumorigenesis and metastasis.

According to the World Health Organization, corneal blindness constitutes 5.1% of global blindness population. Surgical outcomes have been improved significantly in the treatment of corneal blindness. However, corneal transplantation is limited by global shortage of donor tissue, prompting researchers to explore alternative therapies such as novel ocular pharmaceutics to delay corneal disease progression. Animal models are commonly adopted for investigating pharmacokinetics of ocular drugs. However, this approach is limited by physiological differences in the eye between animals and human, ethical issues and poor bench-to-bedside translatability. Cornea-on-a-chip (CoC) microfluidic platforms have gained great attention as one of the advanced in vitro strategies for constructing physiologically representative corneal models. With significant improvements in tissue engineering technology, CoC integrates corneal cells with microfluidics to recapitulate human corneal microenvironment for the study of corneal pathophysiological changes and evaluation of ocular drugs. Such model, in complement to animal studies, can potentially accelerate translational research, in particular the pre-clinical screening of ophthalmic medication, driving clinical treatment advancement for corneal diseases. This review provides an overview of engineered CoC platforms with respect to their merits, applications, and technical challenges. Emerging directions in CoC technology are also proposed for further investigations, to accentuate preclinical obstacles in corneal research.

Measurement(s) Microarray Analysis Technology Type(s) Microarray Analysis Sample Characteristic - Organism Mus musculus

PurposeWe aim to investigate the effect of sustained hyperglycemia on corneal epithelial wound healing, ocular surface and systemic immune response, and microbiome indices in diabetic mice compared to controls after alkaline chemical injury of the eye.MethodsCorneal alkaline injury was induced in the right eye of Ins2Akita (Akita) mice and wild-type mice. The groups were observed at baseline and subsequently days 0, 3, and 7 after injury. Corneal re-epithelialization was observed under slit lamp with fluorescein staining using a cobalt blue light filter. Enucleated cornea specimens were compared at baseline and after injury for changes in cornea thickness under hematoxylin and eosin staining. Tear cytokine and growth factor levels were measured using protein microarray assay and compared between groups and time points. Flow cytometry was conducted on peripheral blood and ocular surface samples to determine CD3+CD4+ cell count. Fecal samples were collected, and gut microbiota composition and diversity pattern were measured using shotgun sequencing.ResultsAkita mice had significantly delayed corneal wound healing compared to controls. This was associated with a reduction in tear levels of vascular endothelial growth factor A, angiopoietin 2, and insulin growth factor 1 on days 0, 3, and 7 after injury. Furthermore, there was a distinct lack of upregulation of peripheral blood and ocular surface CD3+CD4+ cell counts in response to injury in Akita mice compared to controls. This was associated with a reduction in intestinal microbiome diversity indices in Akita mice compared to controls after injury. Specifically, there was a lower abundance of Firmicutes bacterium M10-2 in Akita mice compared to controls after injury.ConclusionIn diabetic mice, impaired cornea wound healing was associated with an inability to mount systemic and local immune response to ocular chemical injury. Baseline and post-injury differences in intestinal microbial diversity and abundance patterns between diabetic mice and controls may potentially play a role in this altered response.

Background/Aims Although international guidelines for bronchiectasis management have been published in Western countries, there is a lack of data about their application in Asian populations including patients with different phenotypes. We aimed to investigate the current status of bronchiectasis management in Asian populations. Methods A nationwide questionnaire survey was performed of Asian respiratory specialists from South Korea, Japan, Taiwan, Singapore, Vietnam, and Sri Lanka. Participants were invited by e-mail to answer a questionnaire comprising 25 questions based on international guidelines for the management of bronchiectasis. Results A total of 221 physicians participated in the survey. About half of them were Korean (50.2%), with the next most common nationalities being Japanese (23.1%), Taiwanese (13.6%), and Singaporean (7.7%). Only 18 (8.1%) responders had local guidelines for bronchiectasis. While 85 (38.5%) responders checked sputum acid-fast bacillus smear/culture about 1 to 3 times per year, only a small proportion of responders routinely performed a serum immunoglobulin test (36/221, 16.3%) or evaluated for allergic bronchopulmonary aspergillosis (41/221, 18.6%). Less than half (43.4%) of responders performed eradication treatment in patients with drug-sensitive Pseudomonas aeruginosa infection, mainly due to the limited availability of inhaled antibiotics (34.8%). In addition, 58.6% of responders considered physiotherapy such as airway clearance and pulmonary rehabilitation. Conclusions Discrepancies might exist between guideline recommendations and practice for bronchiectasis management in Asian populations, partly due to the limited availability of treatment in each country. The development of local guidelines that consider the phenotypes and situation will help to standardize and improve the management of bronchiectasis.

Remanufacturing has been gaining increasing attention in the last few years as a part of green engineering. It is the process of restoring the original specifications of a given product utilizing a combination of new, repaired, and old parts. The present study investigates non-destructive disassembly of an interference fit pin-hub joint to enable the reuse of worn parts with the same loading capacity. The aim is to reduce the disassembly force while preventing plastic deformation and frictional damage on the contact surface to avoid fretting failure and enable further coating. A finite element model of a shaft/hub interference fit was developed, taking into account two cases of damage to the mating parts: deformation and corrosion. The results indicate that thermal disassembly is effective in reducing breaking force by 50% in deformed joints, whereas vibration waves are more suitable for corroded parts with increased friction. In addition, applying a low-frequency oscillation force to the axis of disassembly reduces the pulling out force by 5% and plastic deformation by 99% due to acoustic softening effects. Furthermore, using a heat flux simultaneously with vibration decreases the breaking force by 85%, indicating the higher effectiveness of thermal-aided disassembly and vibration-assisted disassembly in reducing the breaking force of corroded parts with increased friction. This study provides remanufacturing designers with efficient tools to weaken the interference fit and decrease the disconnecting force, ultimately reducing the cost and time required for the disassembly process.

Endocrine therapy has been the mainstay for hormone responsive breast cancer treatment. Here, Garcia-Martinez and colleagues discuss epigenetic mechanisms regulating ER + breast cancer and endocrine therapy resistance, and highlight approaches to rewire the cancer epigenome to improve targeted therapies for this cancer.

This study provides an accurate and efficient method to reconstruct detailed and high-resolution digital 3D models of carpological materials by photogrammetric method, in which only about 100 to 150 images are required for each model reconstruction. The 3D models reflect the realistic morphology and genuine color of the carpological materials. The 3D models are scaled to represent the true size of the materials even as small as 3 mm in diameter. The interfaces are interactive, in which the 3D models can be rotated in 360° to observe the structures and be zoomed to inspect the macroscopic details. This new platform is beneficial for developing a virtual herbarium of carpological collection which is thus the most important to botanical authentication and education.

BackgroundBladder cancer is the tenth most common cancer in the United Kingdom. Currently, open radical cystectomy (ORC) is the gold standard. Due to the risk of complications and a 2.3-8% mortality rate1, there is growing interest in the use of robot-assisted radical cystectomy (RARC). The aim of this study is to perform a cost-utility analysis, comparing RARC to ORC for bladder cancer patients from the perspective of the National Health Service England.MethodsA three-stage decision tree: surgery, post-surgery transfusions and complications, in a 90-day time horizon, was produced to simulate possible pathways of patients. The incremental cost-effectiveness ratio (ICER) was calculated based on data derived from current literature. Multiple univariate sensitivity analysis was carried out to evaluate influences of varying costs of RARC and ORC on the ICER.ResultsThe ICER for RARC compared to ORC resulted in £25,536/QALY. At the lower threshold of £20,000/QALY, RARC resulted in a negative NMB (£-4,843.32) and at the upper threshold of £30,000/QALY, a positive NMB (£624.61) compared to ORC. Threshold analysis showed that the intervention costs of £13,497 and £14,403 are met at the lower and upper threshold respectively. The univariate sensitivity analysis showed that the intervention costs of RARC or ORC, and the probabilities of complications, had the greatest impact on the ICER.ConclusionAs the resultant ICER did not fall below the £20,000/QALY threshold, our study did not provide a definitive recommendation for RARC for bladder cancer. Negative values for the NMB at the lower threshold indicated the intervention was not feasible from a cost perspective. At the upper threshold of £30,000/QALY, this situation was reversed. The intervention became cost-effective. Therefore, further research is needed to justify the intervention.

Deforestation of native tropical forests has occurred extensively over several decades. The plantation of fast-growing trees, such as Acacia spp., is expanding rapidly in tropical regions, which can contribute to conserve the remaining native tropical forests. To better understand belowground biogeochemical cycles and the sustainable productivity of acacia plantations, we assessed the effects of vegetation (acacia plantations vs. native forests) and soil types (Oxisols vs. Ultisols) on soil properties, including the diversity and community structures of bacteria- and fungi-colonizing surface and subsurface roots and soil in the Central Highlands of Vietnam. The results in surface soil showed that pH was significantly higher in acacia than in native for Oxisols but not for Ultisols, while exchangeable Al was significantly lower in acacia than in native for Ultisols but not for Oxisols. Bacterial alpha diversity (especially within phylum Chloroflexi) was higher in acacia than in native only for Oxisols but not for Ultisols, which was the same statistical result as soil pH but not exchangeable Al. These results suggest that soil pH, but not exchangeable Al, can be the critical factor to determine bacterial diversity. Acacia tree roots supported greater proportions of copiotrophic bacteria, which may support lower contents of soil inorganic N, compared with native tree roots for both Oxisols and Ultisols. Acacia tree roots also supported greater proportions of plant pathogenic Mycoleptodiscus sp. but appeared to reduce the abundances and diversity of beneficial ECM fungi compared with native tree roots regardless of soil types. Such changes in fungal community structures may threaten the sustainable productivity of acacia plantations in the future.

Stroke has been the leading cause of disability due to the induced spasticity in the upper extremity. The constant flexion of spastic fingers following stroke has not been well described. Accurate measurements for joint stiffness help clinicians have a better access to the level of impairment after stroke. Previously, we conducted a method for quantifying the passive finger joint stiffness based on the pressure-angle relationship between the spastic fingers and the soft-elastic composite actuator (SECA). However, it lacks a ground-truth to demonstrate the compatibility between the SECA-facilitated stiffness estimation and standard joint stiffness quantification procedure. In this study, we compare the passive metacarpophalangeal (MCP) joint stiffness measured using the SECA with the results from our designed standalone mechatronics device, which measures the passive metacarpophalangeal joint torque and angle during passive finger rotation. Results obtained from the fitting model that concludes the stiffness characteristic are further compared with the results obtained from SECA-Finger model, as well as the clinical score of Modified Ashworth Scale (MAS) for grading spasticity. These findings suggest the possibility of passive MCP joint stiffness quantification using the soft robotic actuator during the performance of different tasks in hand rehabilitation.

Strokes cause severe impairment of hand function because of the spasticity in the affected upper extremities. Proper spasticity evaluation is critical to facilitate neural plasticity for rehabilitation after stroke. However, existing methods for measuring spasticity, e.g. Modified Ashworth Scale (MAS), highly depends on clinicians’ experiences, which are subjective and lacks quantitative details. Here, we introduce the first rehabilitation actuator that objectively reflects the condition of post-stroke finger spasticity. The actuator is 3D printed with soft materials. By considering the finger and the actuator together, the spasticity, i.e. stiffness, in finger is obtained from the pressure–angle relationship. The method is validated by simulations using finite element analysis (FEA) and experiments on mannequin fingers. Furthermore, it is examined on four stroke subjects and four healthy subjects. Results show the finger stiffness increases significantly from healthy subjects to stroke subjects, particularly those with high MAS score. For patients with the same MAS score, stiffness variation can be a few times. With this soft actuator, a hand rehabilitation robot that may tell the therapeutic progress during the rehabilitation training is readily available.

Kaposi's sarcoma (KS) is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV). Unanswered questions regarding KS are its cellular ontology and the conditions conducive to viral oncogenesis. We identify PDGFRA(+)/SCA-1(+) bone marrow-derived mesenchymal stem cells (Pα(+)S MSCs) as KS spindle-cell progenitors and found that pro-angiogenic environmental conditions typical of KS are critical for KSHV sarcomagenesis. This is because growth in KS-like conditions generates a de-repressed KSHV epigenome allowing oncogenic KSHV gene expression in infected Pα(+)S MSCs. Furthermore, these growth conditions allow KSHV-infected Pα(+)S MSCs to overcome KSHV-driven oncogene-induced senescence and cell cycle arrest via a PDGFRA-signaling mechanism; thus identifying PDGFRA not only as a phenotypic determinant for KS-progenitors but also as a critical enabler for viral oncogenesis.

The role of Polycomb Repressive Complex 1 (PRC1) is well described in development. Here, the authors investigate canonical PRC1’s regulation of transcriptional programs in breast cancer where, in addition to its repressive function, it is also recruited to oncogenic active enhancers to regulate enhancer activity and chromatin accessibility.

Globally, approximately 11% of all infants are born preterm, prior to 37 weeks’ gestation. In these high-risk neonates, encephalopathy of prematurity (EoP) is a major cause of both morbidity and mortality, especially for neonates who are born very preterm (

Abstract Background Gastric cancer (GC) is one of the frequent causes of cancer-related death in eastern Asian population. IGF2BP2 lists in the top rank up-regulated genes in GC, but its functional role is unclear. Method The expression of IGF2BP3 in GC cell lines and primary samples was examined by qRT-PCR and Western blot. The biological role of IGF2BP3 was revealed by a series of functional in vitro studies. Its regulation by microRNAs (miRNAs) was predicted by TargetScan and confirmed by luciferase assays and rescue experiments. Results IGF2BP3 ranked the No.1 of the up-regulated genes by expression microarray analysis in GC cell lines. The expression level of IGF2BP3 was observed in GC tissues comparing with non-tumorous gastric epitheliums. The up-regulated IGF2BP3 expression was associated with poor disease specific survival. IGF2BP3 knockdown significantly inhibited cell proliferation and invasion. Apart from copy number gain, IGF2BP3 has been confirmed to be negatively regulated by tumor-suppressive miRNA, namely miR-34a. The expression of miR-34a showed negative correlation with IGF2BP3 mRNA expression in primary GC samples and more importantly, re-overexpression of IGF2BP3 rescued the inhibitory effect of miR-34a. Conclusion We compressively revealed the oncogenic role of IGF2BP3 in gastric tumorigenesis and confirmed its activation is partly due to the silence of miR-34a. Our findings identified useful prognostic biomarker and provided clinical translational potential.

The classical view of cell death has long assumed that, once initiated, the dying process is irreversible. However, recent studies reveal that recovery of dying cells can actually occur, even after initiation of a cell suicide process called apoptosis. This discovery raised fundamental key questions about which forms of the cell death process could be reversible and how reversal is mediated. Here, we uncover an unanticipated reversibility of ferroptotic cell death process. Unlike apoptosis reversal, removal of ferroptosis inducers, such as erastin and glutamate, is insufficient to allow ferroptotic dying cells to escape the cell death process. However, by removing the cell death inducer and providing the reduced form of glutathione or the radical-trapping antioxidant ferrostatin-1, ferroptotic dying cells can be rescued and promoted to recover. Interestingly, although ferroptotic inhibitors such as aminooxyacetic acid, deferoxamine, dopamine and vitamin C can prevent initiation of ferroptosis, added alone they are unable to reverse the initiated ferroptosis, suggesting regulatory distinctions between preventing and reversing ferroptosis. Together, these results reveal the first evidence that ferroptosis is reversible and suggest strategies to enhance its reversibility, thereby providing a useful model for studying the physiological, pathological and therapeutic potentials of this cell recovery process.

Most associative learning tests in rodents use negative stimuli, such as electric shocks. We investigated if young rats can learn to associate the presence of an odour with the experience of being tickled (i.e. using an experimenter's hand to mimic rough-and-tumble play), shown to elicit 50 kHz ultrasonic vocalisations (USVs), which are indicative of positive affect. Male, pair-housed Wistar rats (N = 24) were all exposed to two neutral odours (A and B) presented in a perforated container on alternate days in a test arena. Following 60s of exposure, the rats were either tickled on days when odour A (n = 8) or odour B (n = 8) was present, or never tickled (n = 8). When tickled, rats produced significantly more 50 kHz USVs compared to the days when not being tickled, and compared to control rats. The level of anticipatory 50 kHz USVs in the 60s prior to tickling did not differ significantly between the tickled and control rats. As a retrieval test following the odour conditioning, rats were exposed successively in the same arena to three odours: an unknown neutral odour, extract of fox faeces, and either odours A or B. Compared to controls, 50 kHz USVs of tickled rats increased when exposed to the odour they had previously experienced when tickled, indicating that these rats had learned to associate the odour with the positive experience of being tickled. In a test with free access for 5 min to both arms of a T-maze, each containing one of the odours, rats tickled with odour A spent more time in the arm with this odour. This work is the first to test in a fully balanced design whether rats can learn to associate an odour with tickling, and indicates that positive odour conditioning has potential to be used as an alternative to negative conditioning tests.

Necrotizing pneumonia induced by Mycobacterium tuberculosis is a rare but severe condition. It is difficult to distinguish between M. tuberculosis-associated and bacterial necrotizing pneumonia. The optimal treatment for this condition is controversial. Here, we report a case of M. tuberculosis-associated necrotizing pneumonia treated with the adjunctive corticosteroid and the antituberculosis drugs.

In this paper, we propose an RFID-based location-positioning platform for managing cart operations at vast and fast-moving distribution facilities. Our work was motivated by a real-world problem in a large airmail center. Our system requires that each cart is affixed with an active RFID tag, and RFID readers are installed at multiple locations of the facility. The locations of the tagged carts are determined by the estimated angles of arrival communication signals between the readers and the tags and the signal strengths, and the information about their positions are stored in the platform continuously. This platform enables the users to locate tagged objects in real time, thereby saving staff members a significant amount of time from searching for the right carts in the highly dynamic environment. Consequently, the mail facility can benefit from the increased efficiency. Furthermore, the system is also able to reduce the chance of having a delay in delivering mail bags to unit load device (ULD) area and misplacements of mail bags to ULDs. We further analyze the the huge amount of historical data collected from the RFID infrastructure of the airmail center for the cart movements within the facility and observed previously unrecognized operational issues. We also discuss some of the challenges and problems faced in this project. We believe that this application can bring huge benefits to businesses and organizations along supply chains by effectively anticipating the increasing demand for logistics services in the age of electronic retailing.

Current guideline-recommended screening for pulmonary hypertension in patients with systemic sclerosis has not been evaluated in systemic lupus erythematosus (SLE), which is disproportionately prevalent in Asians. This multicentre, cross-sectional screening study aims to study the prevalence of pulmonary hypertension among SLE patients using these guidelines, and identify independent predictors and develop a prediction model for pulmonary hypertension in SLE patients. SLE patients from participating centres will undergo an echocardiography- and biomarker-based pulmonary hypertension screening procedure as in the DETECT study. Standard right heart catheterisation will be provided to patients with intermediate or high echocardiographic probability of pulmonary hypertension. Those with low echocardiographic probability will rescreen within 1 year. The primary measure will be the diagnosis and types of pulmonary hypertension and prevalence of pulmonary hypertension in SLE patients. The secondary measures will be the predictors and prediction models for pulmonary hypertension in SLE patients. The estimated sample size is approximately 895 participants. The results of the SOPHIE study will be an important contribution to the literature of SLE-related pulmonary hypertension and may be immediately translatable to real clinical practice. Ultimately, this study will provide the necessary evidence for establishing universal guidelines for screening of pulmonary hypertension in SLE patients.

Anastasis is a natural cell recovery phenomenon that rescues cells from the brink of death. Programmed cell death such as apoptosis has been traditionally assumed to be an intrinsically irreversible cascade that commits cells to a rapid and massive demolition. Interestingly, recent studies have demonstrated recovery of dying cells even at the late stages generally considered immutable. Here, we examine the evidence for anastasis in cultured cells and in animals, review findings illuminating the potential mechanisms of action, discuss the challenges of studying anastasis and explore new strategies to uncover the function and regulation of anastasis, the identification of which has wide-ranging physiological, pathological and therapeutic implications.

Anastasis (Greek for "rising to life") is a cell recovery phenomenon that rescues dying cells from the brink of cell death. We recently discovered anastasis to occur after the execution-stage of apoptosis in vitro and in vivo. Promoting anastasis could in principle preserve injured cells that are difficult to replace, such as cardiomyocytes and neurons. Conversely, arresting anastasis in dying cancer cells after cancer therapies could improve treatment efficacy. To develop new therapies that promote or inhibit anastasis, it is essential to identify the key regulators and mediators of anastasis – the therapeutic targets. Therefore, we performed time-course microarray analysis to explore the molecular mechanisms of anastasis during reversal of ethanol-induced apoptosis in mouse primary liver cells. We found striking changes in transcription of genes involved in multiple pathways, including early activation of pro-cell survival, anti-oxidation, cell cycle arrest, histone modification, DNA-damage and stress-inducible responses, and at delayed times, angiogenesis and cell migration. Validation with RT-PCR confirmed similar changes in the human liver cancer cell line, HepG2, during anastasis. Here, we present the time-course whole-genome gene expression dataset revealing gene expression profiles during the reversal of apoptosis. This dataset provides important insights into the physiological, pathological, and therapeutic implications of anastasis.