Targeting cathepsin S promotes activation of OLF1-BDNF/TrkB axis to enhance cognitive function.

BACKGROUND: Cathepsin S (CTSS) is a cysteine protease that played diverse roles in immunity, tumor metastasis, aging and other pathological alterations. At the cellular level, increased CTSS levels have been associated with the secretion of pro-inflammatory cytokines and disrupted the homeostasis of Ca2+ flux. Once CTSS was suppressed, elevated levels of anti-inflammatory cytokines and changes of Ca2+ influx were observed. These findings have inspired us to explore the potential role of CTSS on cognitive functions. METHODS: We conducted classic Y-maze and Barnes Maze tests to assess the spatial and working memory of Ctss-/- mice, Ctss+/+ mice and Ctss+/+ mice injected with the CTSS inhibitor (RJW-58). Ex vivo analyses including long-term potentiation (LTP), Golgi staining, immunofluorescence staining of sectioned whole brain tissues obtained from experimental animals were conducted. Furthermore, molecular studies were carried out using cultured HT-22 cell line and primary cortical neurons that treated with RJW-58 to comprehensively assess the gene and protein expressions. RESULTS: Our findings reported that targeting cathepsin S (CTSS) yields improvements in cognitive function, enhancing both working and spatial memory in behavior models. Ex vivo studies showed elevated levels of long-term potentiation levels and increased synaptic complexity. Microarray analysis demonstrated that brain-derived neurotrophic factor (BDNF) was upregulated when CTSS was knocked down by using siRNA. Moreover, the pharmacological blockade of the CTSS enzymatic activity promoted BDNF expression in a dose- and time-dependent manner. Notably, the inhibition of CTSS was associated with increased neurogenesis in the murine dentate gyrus. These results suggested a promising role of CTSS modulation in cognitive enhancement and neurogenesis. CONCLUSION: Our findings suggest a critical role of CTSS in the regulation of cognitive function by modulating the Ca2+ influx, leading to enhanced activation of the BDNF/TrkB axis. Our study may provide a novel strategy for improving cognitive function by targeting CTSS.

Low-cost dual-energy CBCT by spectral filtration of a dual focal spot X-ray source.

Dual-energy cone beam computed tomography (DE-CBCT) has been shown to provide more information and improve performance compared to a conventional single energy spectrum CBCT. Here we report a low-cost DE-CBCT by spectral filtration of a carbon nanotube x-ray source array. The x-ray photons from two focal spots were filtered respectively by a low and a high energy filter. Projection images were collected by alternatively activating the two beams while the source array and detector rotated around the object, and were processed by a one-step materials decomposition and reconstruction method. The performance of the DE-CBCT scanner was evaluated by imaging a water-equivalent plastic phantom with inserts containing known densities of calcium or iodine and an anthropomorphic head phantom with dental implants. A mean energy separation of 15.5 keV was achieved at acceptable dose rates and imaging time. Accurate materials quantification was obtained by materials decomposition. Metal artifacts were reduced in the virtual monoenergetic images synthesized at high energies. The results demonstrated the feasibility of high quality DE-CBCT imaging by spectral filtration without using either an energy sensitive detector or rapid high voltage switching.

A carbon nanotube x-ray source array designed for a new multisource cone beam computed tomography scanner.

Cone beam computed tomography (CBCT) is known to suffer from strong scatter and cone beam artifacts. The purpose of this study is to develop and characterize a rapidly scanning carbon nanotube (CNT) field emission x-ray source array to enable a multisource CBCT (ms-CBCT) image acquisition scheme which has been demonstrated to overcome these limitations. A CNT x-ray source array with eight evenly spaced focal spots was designed and fabricated for a medium field of view ms-CBCT for maxillofacial imaging. An external multisource collimator was used to confine the radiation from each focal spot to a narrow cone angle. For ms-CBCT imaging, the array was placed in the axial direction and rapidly scanned while rotating continuously around the object with a flat panel detector. The x-ray beam profile, temporal and spatial resolutions, energy and dose rate were characterized and evaluated for maxillofacial imaging. The CNT x-ray source array achieved a consistent focal spot size of 1.10 ± 0.04 mm × 0.84 ± 0.03 mm and individual beam cone angle of 2.4°±0.08 after collimation. The x-ray beams were rapidly switched with a rising and damping times of 0.21 ms and 0.19 ms, respectively. Under the designed operating condition of 110 kVp and 15 mA, a dose rate of 8245µGy s-1was obtained at the detector surface with the inherent Al filtration and 2312µGy s-1with an additional 0.3 mm Cu filter. There was negligible change of the x-ray dose rate over many operating cycles. A ms-CBCT scan of an adult head phantom was completed in 14.4 s total exposure time for the imaging dose in the range of that of a clinical CBCT scanner. A spatially distributed CNT x-ray source array was designed and fabricated. It has enabled a new multisource CBCT to overcome some of the main inherent limitations of the conventional CBCT.

Improving the accuracy of bone mineral density using a multisource CBCT.

Multisource cone beam computed tomography CBCT (ms-CBCT) has been shown to overcome some of the inherent limitations of a conventional CBCT. The purpose of this study was to evaluate the accuracy of ms-CBCT for measuring the bone mineral density (BMD) of mandible and maxilla compared to the conventional CBCT. The values measured from a multi-detector CT (MDCT) were used as substitutes for the ground truth. An anthropomorphic adult skull and tissue equivalent head phantom and a homemade calibration phantom containing inserts with varying densities of calcium hydroxyapatite were imaged using the ms-CBCT, the ms-CBCT operating in the conventional single source CBCT mode, and two clinical CBCT scanners at similar imaging doses; and a clinical MDCT. The images of the anthropomorphic head phantom were reconstructed and registered, and the cortical and cancellous bones of the mandible and the maxilla were segmented. The measured CT Hounsfield Unit (HU) and Greyscale Value (GV) at multiple region-of-interests were converted to the BMD using scanner-specific calibration functions. The results from the various CBCT scanners were compared to that from the MDCT. Statistical analysis showed a significant improvement in the agreement between the ms-CBCT and MDCT compared to that between the CBCT and MDCT.

Synthetic interpolated DSA for radiation exposure reduction via gamma variate contrast flow modeling: a retrospective cohort study.

BACKGROUND: Digital subtraction angiography (DSA) yields high cumulative radiation dosages (RD) delivered to patients. We present a temporal interpolation of low frame rate angiograms as a method to reduce cumulative RDs. METHODS: Patients undergoing interventional evaluation and treatment of cerebrovascular vasospasm following subarachnoid hemorrhage were retrospectively identified. DSAs containing pre- and post-intervention runs capturing the full arterial, capillary, and venous phases with at least 16 frames each were selected. Frame rate reduction (FRR) of the original DSAs was performed to 50%, 66%, and 75% of the original frame rate. Missing frames were regenerated by sampling a gamma variate model (GVM) fit to the contrast response curves to the reduced data. A formal reader study was performed to assess the diagnostic accuracy of the "synthetic" studies (sDSA) compared to the original DSA. RESULTS: Thirty-eight studies met inclusion criteria (average RD 1,361.9 mGy). Seven were excluded for differing views, magnifications, or motion. GVMs fit to 50%, 66%, and 75% FRR studies demonstrated average voxel errors of 2.0 ± 2.5% (mean ± standard deviation), 6.5 ± 1.5%, and 27 ± 2%, respectively for anteroposterior projections, 2.0 ± 2.2%, 15.0 ± 3.1%, and 14.8 ± 13.0% for lateral projections, respectively. Reconstructions took 0.51 s/study. Reader studies demonstrated an average rating of 12.8 (95% CI 12.3-13.3) for 75% FRR, 12.7 (12.2-13.2) for 66% FRR and 12.0 (11.5-12.5) for 50% FRR using Subjective Image Grading Scale. Kendall's coefficient of concordance resulted in W = 0.506. CONCLUSION: FRR by 75% combined with GVM reconstruction does not compromise diagnostic quality for the assessment of cerebral vasculature. RELEVANCE STATEMENT: Using this novel algorithm, it is possible to reduce the frame rate of DSA by as much as 75%, with a proportional reduction in radiation exposure, without degrading imaging quality. KEY POINTS: • DSA delivers some of the highest doses of radiation to patients. • Frame rate reduction (FRR) was combined with bolus tracking to interpolate intermediate frames. • This technique provided a 75% FRR with preservation of diagnostic utility as graded by a formal reader study for cerebral angiography performed for the evaluation of cerebral vasospasm. • This approach can be applied to other types of angiography studies.

CSMed® wound dressing for prophylaxis and management of radiation dermatitis in breast and head-neck cancer patients: a single hospital prospective clinical trial.

PURPOSE: CSMed® wound dressing, a dressing with various herb extracts, was tested for its therapeutic effect in radiation dermatitis of breast and head-and-neck cancer patients. METHODS: This study included 20 breast cancer patients and 10 head-and-neck cancer patients. Half of the irradiated area was covered with CSMed® and the other half was under routine treatment. The severity of radiation dermatitis was evaluated with radiation therapy oncology group (RTOG) grade throughout the treatment and the follow-up period. The RTOG grade between the dressed and undressed area were compared to illustrate the therapeutic effect of CSMed® dressing. RESULTS: The results showed that CSMed® dressed area had significant lower RTOG score at 3-7 weeks and final record during the treatment, and 1-3 weeks during follow-up than undressed area. CONCLUSIONS: This indicated that CSMed® can delay the onset, reduce the severity, and enhance healing of radiation dermatitis. CSMed® can be used for prophylaxis and management of radiation dermatitis.

ANCA-associated vasculitis presenting with isolated neurological manifestations in a patient with cocaine abuse: a case report and literature review.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of rare conditions predominantly affecting small vessels of skin, musculoskeletal, pulmonary, renal, and rarely central and peripheral nervous systems. Isolated neurological manifestations of AAV are uncommon and challenging to diagnose. Cocaine has been reported as a potential trigger for the development of AAV. There are only a few case reports of isolated neurological involvement in cocaine-induced AAV with poorly characterized histopathological features. We present a unique case of AAV with isolated neurological manifestations presenting with multiple cranial neuropathies, leptomeningeal enhancement on imaging and histopathologic evidence of small-vessel vasculitis in the leptomeninges and brain and extensive dural fibrosis in a patient with cocaine abuse. The patient's progressive neurological deficits were controlled after starting immunosuppression with rituximab and prednisone. We also reviewed the literature to provide the diagnostic overview of AAV and evaluate intervention options. To our knowledge, this is the first case of AAV with isolated neurological manifestations and histopathologic evidence of small-vessel vasculitis in a patient with cocaine abuse. Patients with multiple cranial neuropathies and meningeal involvement should be screened for AAV, especially if they have a history of cocaine abuse.

A phase I trial of caffeine to evaluate safety in infants with hypoxic-ischemic encephalopathy.

OBJECTIVE: Caffeine provides neuroprotection following hypoxic-ischemic injury in animals. We characterized the safety of escalating doses of caffeine in infants with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia. STUDY DESIGN: Phase I trial of infants undergoing therapeutic hypothermia for HIE receiving IV caffeine 20 mg/kg followed by up to two daily doses of 5 mg/kg (n = 9) or 10 mg/kg (n = 8). Safety was evaluated based on adverse events and frequency of pre-specified outcomes compared to data from the Whole-Body Hypothermia for HIE trial (Shankaran, 2005). RESULTS: Twelve of 17 (71%) infants had ≥1 adverse event during the study period. The frequency of clinical outcomes related to HIE were not statistically different from outcomes in infants receiving hypothermia in the Whole-Body Hypothermia for HIE trial. CONCLUSION: Caffeine administration was well tolerated. A larger study is required to determine the optimal dose and evaluate drug safety and efficacy. CLINICAL TRIAL: ClinicalTrials.gov Identifier: NCT03913221.

Polycythemia Secondary to Renal Hemangioblastoma: A Case Report and Literature Review.

Secondary polycythemia is a paraneoplastic syndrome observed in tumors with excessive erythropoietin (EPO) production. Renal cell carcinoma (RCC) and cerebellar hemangioblastoma are the 2 most well-known tumors to induce secondary polycythemia. Hemangioblastomas occurring in the kidney are rare. In this work we present a case of renal hemangioblastoma that caused erythrocytosis in a 19-year-old man. We demonstrated intratumoural EPO production by immunohistochemistry, and conducted whole-exome sequencing to evaluate possible genetic alterations that reported to induce tumor-related polycythemia. In spite of an indolent clinical behavior, renal hemangioblastoma is difficult to differentiate from RCC not only clinically, but also histopathologically. Given that RCC is the most well-known renal tumor to induce erythrocytosis, the uncommon manifestation of polycythemia in renal hemangioblastoma, as shown in our case, can cause further diagnostic challenges. Renal hemangioblastoma should be listed in the differential diagnoses of renal tumors presenting with erythrocytosis, apart from the most common RCC.

Uterine Uptake of Estrogen and Progestogen-Based Radiotracers in Rhesus Macaques with Endometriosis.

PURPOSE: Endometriosis is an estrogen-dependent disorder of menstruating primates where tissues similar to the inner lining of the uterus exist "ectopically" outside of the uterus. The ectopic endometrium, like the endometrium within the uterus, expresses estrogen receptors (ER) and progesterone receptors (PR) and undergoes hormone-dependent cell proliferation and bleeding each menstrual cycle. The goal of this study was to conduct abdominopelvic positron emission tomography (PET) scans with computed tomography (CT) imaging of rhesus macaques (Macaca mulatta) using radiotracers that target ER and PR [16α-[18F]fluoroestradiol (FES) and 12-[18F]fluoro-furanyl-nor-progesterone (FFNP)] in individuals with and without endometriosis. We also aimed to determine if menstrual cycle phase and/or the presence of endometriosis affected the uptake of these radiotracers. PROCEDURES: Rhesus macaques with either clinically diagnosed endometriosis (n = 6) or no endometriosis (n = 4) underwent PET/CT scans with FES. A subset of the animals also underwent PET/CT scans with FFNP. Standard uptake values corrected for body weight (SUVs) were obtained for each radiotracer in target and background tissues (e.g., intestinal). We performed repeated measure analysis of variance tests to determine how uterine and background uptake differed with scan time, phase of the menstrual cycle, and disease state. RESULTS: Abdominopelvic PET/CT could not resolve small, individual endometriotic lesions. However, macaques with endometriosis displayed higher uterine uptake compared to those without the disorder. Radiotracer uptake differed by menstrual cycle phase with increased uterine uptake of both radiotracers in the proliferative phase of the menstrual cycle. Background intestinal uptake of FFNP increased over time after infusion, but only during the proliferative phase. CONCLUSIONS: PET/CT with FES and FFNP support the concept that ER and PR levels are altered in individuals with endometriosis. This highlights the impact of the disease on typical reproductive tract function and may provide a novel pathway for the identification of individuals with endometriosis.

Internet use time and subjective well-being during the COVID-19 outbreak: serial mediation of problematic internet use and self-esteem.

The coronavirus disease (COVID-19) outbreak is a threat to adolescents' mental health and livelihoods, and lowers their subjective well-being (SWB). Expanding on previous literatures, this study examined whether internet use time was related to SWB and whether this relationship was mediated by problematic internet use (PIU) and self-esteem during the COVID-19 outbreak. In Taiwan, the COVID-19 epidemic broke out in February, 2020. During March 2 to 27, this study recruited a total of 1,060 adolescents from junior high schools by both stratified and cluster sampling, and administered a comprehensive investigation. The results displayed that SWB was significantly and negatively predicted by internet use time. PIU fully mediated the relationship. Moreover, PIU predicted a decrease of self-esteem, which played a full mediation role between PIU and SWB. The results provide evidence in explaining how increased internet use time is associated with a greater level of PIU, which relates to lower self-esteem, correlating with lower SWB in adolescents. This study can provide reference to mental health organizations and educational agencies to design appropriate SWB promotion programs for the junior high school population in terms of epidemic prevention.

Role of DCLK1/Hippo pathway in type II alveolar epithelial cells differentiation in acute respiratory distress syndrome.

BACKGROUND: Delay in type II alveolar epithelial cell (AECII) regeneration has been linked to higher mortality in patients with acute respiratory distress syndrome (ARDS). However, the interaction between Doublecortin-like kinase 1 (DCLK1) and the Hippo signaling pathway in ARDS-associated AECII differentiation remains unclear. Therefore, the objective of this study was to understand the role of the DCLK1/Hippo pathway in mediating AECII differentiation in ARDS. MATERIALS AND METHODS: AECII MLE-12 cells were exposed to 0, 0.1, or 1 µg/mL of lipopolysaccharide (LPS) for 6 and 12 h. In the mouse model, C57BL/6JNarl mice were intratracheally (i.t.) injected with 0 (control) or 5 mg/kg LPS and were euthanized for lung collection on days 3 and 7. RESULTS: We found that LPS induced AECII markers of differentiation by reducing surfactant protein C (SPC) and p53 while increasing T1α (podoplanin) and E-cadherin at 12 h. Concurrently, nuclear YAP dynamic regulation and increased TAZ levels were observed in LPS-exposed AECII within 12 h. Inhibition of YAP consistently decreased cell levels of SPC, claudin 4 (CLDN-4), galectin 3 (LGALS-3), and p53 while increasing transepithelial electrical resistance (TEER) at 6 h. Furthermore, DCLK1 expression was reduced in isolated human AECII of ARDS, consistent with the results in LPS-exposed AECII at 6 h and mouse SPC-positive (SPC+) cells after 3-day LPS exposure. We observed that downregulated DCLK1 increased p-YAP/YAP, while DCLK1 overexpression slightly reduced p-YAP/YAP, indicating an association between DCLK1 and Hippo-YAP pathway. CONCLUSIONS: We conclude that DCLK1-mediated Hippo signaling components of YAP/TAZ regulated markers of AECII-to-AECI differentiation in an LPS-induced ARDS model.

Climate change, air quality, and respiratory health: a focus on particle deposition in the lungs.

This review article delves into the multifaceted relationship between climate change, air quality, and respiratory health, placing a special focus on the process of particle deposition in the lungs. We discuss the capability of climate change to intensify air pollution and alter particulate matter physicochemical properties such as size, dispersion, and chemical composition. These alterations play a significant role in influencing the deposition of particles in the lungs, leading to consequential respiratory health effects. The review paper provides a broad exploration of climate change's direct and indirect role in modifying particulate air pollution features and its interaction with other air pollutants, which may change the ability of particle deposition in the lungs. In conclusion, climate change may play an important role in regulating particle deposition in the lungs by changing physicochemistry of particulate air pollution, therefore, increasing the risk of respiratory disease development.

Climate change influences particle deposition in the lungs by modifying the physicochemical properties of particulate air pollution, thereby escalating the risk of respiratory disease development.It is crucial for healthcare providers to educate patients about the relationship between climate change and respiratory health.People with conditions such as asthma, COPD, and allergies must understand how changes in weather, air pollution, and allergens can exacerbate their symptoms.Instruction on understanding air quality indices and pollen predictions, along with recommendations on adapting everyday activities and medication regimens in response, is essential.

The fermented product of high-yield surfactin strain Bacillus subtilis LYS1 improves the growth performance and intestinal villi morphology in broilers.

This study aimed to select Bacillus spp. for surfactin production by solid-state fermentation and to investigate the physiochemical characterizations of the fermented product (FP) and its effect on growth performance, carcass trait, intestinal morphology, and clinical blood biochemistry of broilers. Accordingly, the correlations between the functional components of FP and the growth performance of broilers are elucidated. Four hundred eighty 1-day-old Ross 308 broiler chicks were randomly assigned to dietary supplementation of 2.5% fish meal, 2.5% unfermented product, or 2.5% FP produced by Bacillus subtilis LYS1 (LYS1), Bacillus amyloliquefaciens Da16, B. subtilis Lo6 (Lo6), B. subtilis NSN7, B. subtilis subsp. natto N21, or B. subtilis N12. Each treatment had 6 replicates. The experimental period was 5 wk. Results showed that the Lo6 showed the highest protease activity among all fermented groups. The LYS1 showed the highest surfactin yields (10.69 mg/g) among all fermented groups (P < 0.05). The weight gain (WG), feed conversion ratio (FCR), and production efficiency factor (PEF) of LYS1 group were significantly better than unfermented group at 0 to 3 and 0 to 5-wk-old (P < 0.05). The Bacillus-like counts and surfactin content of FP were moderately correlated to WG (0.7 > r > 0.3), FCR (-0.3 > r > -0.7), and PEF (0.7 > r > 0.3) at 0 to 3 and 0 to 5-wk-old (P < 0.05). The protease activity of FP was moderately correlated to WG (0.7 > r > 0.3), FCR (-0.3 > r > -0.7), and PEF (0.7 > r > 0.3) at 0 to 3-wk-old (P < 0.05). The villus height to crypt depth ratio in duodenum and jejunum of fish meal group and LYS1 group were higher than unfermented group (P < 0.05). In conclusion, LYS1 shows the highest surfactin yields. Diets supplemented with 2.5% LYS1 FP can improve the growth performance and the development of intestinal villi in broilers. Moreover, this study proves that the surfactin content, Bacillus-like counts, and protease activity of FP show a correlation to the growth performance of broilers.

Autonomous medical needle steering in vivo.

The use of needles to access sites within organs is fundamental to many interventional medical procedures both for diagnosis and treatment. Safely and accurately navigating a needle through living tissue to a target is currently often challenging or infeasible because of the presence of anatomical obstacles, high levels of uncertainty, and natural tissue motion. Medical robots capable of automating needle-based procedures have the potential to overcome these challenges and enable enhanced patient care and safety. However, autonomous navigation of a needle around obstacles to a predefined target in vivo has not been shown. Here, we introduce a medical robot that autonomously navigates a needle through living tissue around anatomical obstacles to a target in vivo. Our system leverages a laser-patterned highly flexible steerable needle capable of maneuvering along curvilinear trajectories. The autonomous robot accounts for anatomical obstacles, uncertainty in tissue/needle interaction, and respiratory motion using replanning, control, and safe insertion time windows. We applied the system to lung biopsy, which is critical for diagnosing lung cancer, the leading cause of cancer-related deaths in the United States. We demonstrated successful performance of our system in multiple in vivo porcine studies achieving targeting errors less than the radius of clinically relevant lung nodules. We also demonstrated that our approach offers greater accuracy compared with a standard manual bronchoscopy technique. Our results show the feasibility and advantage of deploying autonomous steerable needle robots in living tissue and how these systems can extend the current capabilities of physicians to further improve patient care.

Uterine uptake of estrogen and progestogen-based radiotracers in rhesus macaques with endometriosis.

Purpose: Few investigations have examined the uptake of radiotracers that target the prominent sex-steroid receptors in the uterus across the menstrual cycle and with disease state. We aimed to determine if uptake of the radiotracers that target estrogen and progesterone receptors (ER and PR) differ with the presence of endometriosis and/or across the menstrual cycle. We performed PET and computed tomography (CT) imaging procedures on rhesus macaques (Macaca mulatta) using 16α-[18F]fluoroestradiol (FES) and 21-[18F]fluoro-furanyl-nor-progesterone (FFNP) in individuals with and without endometriosis in the proliferative and secretory phases of the menstrual cycle. Procedures: Macaques with either clinically diagnosed endometriosis (n = 6) or no endometriosis (n = 4) underwent abdominopelvic PET/CT scans with FES. A subset of these animals also underwent PET/CT scans with FFNP. Standard uptake values corrected for body weight (SUVbw) were obtained for each radiotracer in target and background tissues (i.e., intestinal and muscle). We performed repeated measure analysis of variance tests to determine how uterine and background uptake differed with scan time, phase of the menstrual cycle, and disease state. Results: PET/CT could not resolve small, individual endometriotic lesions. However, uterine uptake of both radiotracers was elevated in the proliferative phase compared to the secretory phase of the menstrual cycle. Intestinal uptake exhibited greater variation during the proliferative phase compared to the secretory phase. Further, intestinal uptake of FFNP increases as the scan progresses, but only during the proliferative phase. Muscle uptake did not differ with menstrual phase or radiotracer type. Lastly, macaques with endometriosis displayed higher uterine uptake of FES compared to those without endometriosis. Conclusions: PET/CT with FES and FFNP support the concept that ER and PR levels are altered in individuals with endometriosis. This highlights the impact of the disease on typical reproductive tract function and may provide a novel pathway for the identification of individuals with endometriosis.

Exon Junction Complex Mediates the Cap-Independent Translation of Circular RNA.

Evidence that circular RNAs (circRNA) serve as protein template is accumulating. However, how the cap-independent translation is controlled remains largely uncharacterized. Here, we show that the presence of intron and thus splicing promote cap-independent translation. By acquiring the exon junction complex (EJC) after splicing, the interaction between circRNA and ribosomes was promoted, thereby facilitating translation. Prevention of splicing by treatment with spliceosome inhibitor or mutating splicing signal hindered cap-independent translation of circRNA. Moreover, EJC-tethering using Cas13 technology reconstituted EJC-dependent circRNA translation. Finally, the level of a coding circRNA from succinate dehydrogenase assembly factor 2 (circSDHAF2) was found to be elevated in the tumorous tissues from patients with colorectal cancer, and shown to be critical in tumorigenesis of colorectal cancer in both cell and murine models. These findings reveal that EJC-dependent control of circSDHAF2 translation is involved in the regulation of oncogenic pathways. IMPLICATIONS: EJC-mediated cap-independent translation of circRNA is implicated in the tumorigenesis of colorectal cancer.

Determinants of residential greenness and its association with prostate cancer risk: A case-control study in Singapore.

BACKGROUND: Exposure to greenness has been shown to be beneficial to health, but few studies have examined the association between residential greenness and prostate cancer (PCa) risk. Our main objectives were to identify the determinants of residential greenness, and to investigate if residential greenness was associated with PCa risk in Singapore. METHODS: The hospital-based case-control study was conducted between April 2007 and May 2009. The Singapore Prostate Cancer Study (SPCS) comprised 240 prostate cancer cases and 268 controls, whose demographics and residential address were collected using questionnaires. Residential greenness was measured by normalized difference vegetation index (NDVI) around the participants' homes using a buffer size of 1 km. Determinants of NDVI were identified using a multivariable linear regression model. Logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of associations between NDVI and PCa risk, adjusting for potential confounders. RESULTS: Having a BMI within the second quartile, as compared to the lowest quartile, was associated with higher levels of NDVI (ß-coefficient = 0.263; 95% CI = 0.040-0.485) after adjusting for covariates. Additionally, being widowed or separated, as compared to being married, was associated with lower levels of NDVI (ß-coefficient = -0.393; 95% CI = -0.723, -0.063). An interquartile range (IQR) increase in NDVI was positively associated with prostate cancer risk OR = 1.45; 95% CI = 1.02-2.07). Stratified analysis by tumour grade and stage showed that higher NDVI was associated with higher risk of low grade PCa. CONCLUSION: Our findings suggested that residential greenness was associated with higher risk of PCa in Singapore. Future studies on the quality and type of green spaces, as well as other factors of residential greenness, in association with PCa risk should be conducted to better understand this relationship.

The impact of air pollution on respiratory diseases in an era of climate change: A review of the current evidence.

The impacts of climate change and air pollution on respiratory diseases present significant global health challenges. This review aims to investigate the effects of the interactions between these challenges focusing on respiratory diseases. Climate change is predicted to increase the frequency and intensity of extreme weather events amplifying air pollution levels and exacerbating respiratory diseases. Air pollution levels are projected to rise due to ongoing economic growth and population expansion in many areas worldwide, resulting in a greater burden of respiratory diseases. This is especially true among vulnerable populations like children, older adults, and those with pre-existing respiratory disorders. These challenges induce inflammation, create oxidative stress, and impair the immune system function of the lungs. Consequently, public health measures are required to mitigate the effects of climate change and air pollution on respiratory health. The review proposes that reducing greenhouse gas emissions contribute to slowing down climate change and lessening the severity of extreme weather events. Enhancing air quality through regulatory and technological innovations also helps reduce the morbidity of respiratory diseases. Moreover, policies and interventions aimed at improving healthcare access and social support can assist in decreasing the vulnerability of populations to the adverse health effects of air pollution and climate change. In conclusion, there is an urgent need for continuous research, establishment of policies, and public health efforts to tackle the complex and multi-dimensional challenges of climate change, air pollution, and respiratory health. Practical and comprehensive interventions can protect respiratory health and enhance public health outcomes for all.