To explore the role of epigenetic signal molecule bromodomain protein 4 (BRD4) in mediating the therapeutic effect of
(LWDH) Pills on postmenopausal osteoporosis (PMOP) and fatigue.
Thirty rat models ...of PMOP induced by bilateral ovariectomy were randomized equally into two groups for treatment with normal saline (model group) or LWDH Pills (385.7 mg/kg), with another 15 sham-operated rats as the sham operation group. After 12 weeks of treatment, femoral samples were taken to determine the bone density and BRD4 protein expression. The weight-bearing exhaustive swimming time of the rat models was recorded, and serum levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were measured using enzyme-linked immunosorbent assay. In cultured primary osteoblasts the changes in the expressions of BRD4, MAPK and NF-κB proteins were detected by immunofluorescence staining following treatment with LWDH Pills.
The rat models of PMOP showed significantly up-regulated expression of BRD4 pro
Occult peritoneal metastasis (PM) in advanced gastric cancer (AGC) patients is highly possible to be missed on computed tomography (CT) images. Patients with occult PMs are subject to late detection ...or even improper surgical treatment. We therefore aimed to develop a radiomic nomogram to preoperatively identify occult PMs in AGC patients.
A total of 554 AGC patients from 4 centers were divided into 1 training, 1 internal validation, and 2 external validation cohorts. All patients’ PM status was firstly diagnosed as negative by CT, but later confirmed by laparoscopy (PM-positive n = 122, PM-negative n = 432). Radiomic signatures reflecting phenotypes of the primary tumor (RS1) and peritoneum region (RS2) were built as predictors of PM from 266 quantitative image features. Individualized nomograms of PM status incorporating RS1, RS2, or clinical factors were developed and evaluated regarding prediction ability.
RS1, RS2, and Lauren type were significant predictors of occult PM (all P < 0.05). A nomogram of these three factors demonstrated better diagnostic accuracy than the model with RS1, RS2, or clinical factors alone (all net reclassification improvement P < 0.05). The area under curve yielded was 0.958 95% confidence interval (CI) 0.923–0.993, 0.941 (95% CI 0.904–0.977), 0.928 (95% CI 0.886–0.971), and 0.920 (95% CI 0.862–0.978) for the training, internal, and two external validation cohorts, respectively. Stratification analysis showed that this nomogram had potential generalization ability.
CT phenotypes of both primary tumor and nearby peritoneum are significantly associated with occult PM status. A nomogram of these CT phenotypes and Lauren type has an excellent prediction ability of occult PM, and may have significant clinical implications on early detection of occult PM for AGC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This paper proposes a logit-based multi-class ridesharing user equilibrium assignment framework that can incorporate different policy measures such as car restrictions, cordon tolling, and ...subsidization. The framework is formulated as a mixed complementarity problem (MCP). Numerical studies are conducted to illustrate model properties and compare the effects of these measures under different circumstances. The results show that the effectiveness of different policy measures can be greatly influenced by the performance of the transit mode compared with that of the driving mode and the users’ preference for traveling by car. The “cordon toll” policy can be better than the “car restriction” policy in terms of the improvement in social surplus when the performance of the competing transit system is poor. Subsidizing ridesharing (transit fares) using the toll income is the most effective when the performance of the competing transit system is poor (good). It is also found that the implementation of the cordon toll policy cannot effectively promote ridesharing when the performance of the transit system is good.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Over the past decade, the safety of anesthetic agents in children has been questioned after the discovery that immature animals exposed to anesthesia display apoptotic neurodegeneration and long-term ...cognitive deficiencies. We examined the association between exposure to anesthesia in children under age 3 and outcomes in language, cognitive function, motor skills, and behavior at age 10.
We performed an analysis of the Western Australian Pregnancy Cohort (Raine) Study, which includes 2868 children born from 1989 to 1992. Of 2608 children assessed, 321 were exposed to anesthesia before age 3, and 2287 were unexposed.
On average, exposed children had lower scores than their unexposed peers in receptive and expressive language (Clinical Evaluation of Language Fundamentals: Receptive CELF-R and Expressive CELF-E) and cognition (Colored Progressive Matrices CPM). After adjustment for demographic characteristics, exposure to anesthesia was associated with increased risk of disability in language (CELF-R: adjusted risk ratio aRR, 1.87; 95% confidence interval CI, 1.20-2.93, CELF-E: aRR, 1.72; 95% CI, 1.12-2.64), and cognition (CPM: aRR, 1.69; 95% CI, 1.13-2.53). An increased aRR for disability in language and cognition persisted even with a single exposure to anesthesia (CELF-R aRR, 2.41; 95% CI, 1.40-4.17, and CPM aRR, 1.73; 95% CI, 1.04-2.88).
Our results indicate that the association between anesthesia and neuropsychological outcome may be confined to specific domains. Children in our cohort exposed to anesthesia before age 3 had a higher relative risk of language and abstract reasoning deficits at age 10 than unexposed children.
Abstract
Cachexia occurrence and development are associated with loss of white adipose tissues, which may be involved with cancer-derived exosomes. This study attempted to characterize the functional ...mechanisms of breast cancer (BC) cell-derived exosome-loaded microRNA (miR)-155 in cancer cachexia-related fat loss. Exosomes were incubated with preadipocytes and cellular lipid droplet accumulation was observed using Oil Red O staining. Western blotting evaluated the cellular levels of lipogenesis marker peroxisome proliferator activated receptor gamma (PPARγ) and adiponectin, C1Q and collagen domain containing (AdipoQ). Differentiated adipocytes were incubated with exosomes, and phosphate hormone sensitive lipase (P-HSL), adipose triglyceride lipase (ATGL) and glycerol were detected in adipocytes, in addition to uncoupling protein 1 (UCP1) and leptin levels. A mouse model of cancer cachexia was established where cancer exosomes were injected intravenously. The changes in body weight and tumor-free body weights were recorded and serum glycerol levels and lipid accumulation in adipose tissues were determined. Also, the relationship between miR-155 and UBQLN1 was predicted and verified. BC exosome treatment reduced PPARγ and AdipoQ protein levels, promoted the levels of P-HSL and ATGL proteins, facilitated glycerol release, increased UCP1 expression and lowered leptin expression in adipocytes. Exosomal miR-155 inhibited lipogenesis in preadipocytes and boosted the browning of white adipose tissues. miR-155 downregulation alleviated cancer exosome-induced browning of white adipose tissues and fat loss. Mechanistically, miR-155 targeted UBQLN1, and UBQLN1 upregulation reversed the impacts of cancer exosomes. miR-155 loaded by BC cell-derived exosomes significantly affects white adipose browning and inhibition of cancer-derived exosomes.
ABSTRACT
We report the emission variations in PSR J1047−6709 observed at 1369 MHz using the Parkes 64-m radio telescope. This pulsar shows two distinct emission states: a weak state and a bright ...emission state. We detected giant pulses (GPs) in the bright state for the first time. We found 75 GPs with pulse width ranging from 0.6 to 2.6 ms. The energy of GPs follows a power-law distribution with the index α = −3.26 ± 0.22. The peak flux density of the brightest GP is 19 Jy which is 110 times stronger than the mean pulse profile. The polarization properties of the average profile of GPs are similar to that of the pulses with energy less than 10 times average pulse energy in the bright state. This indicates that the emission mechanism is basically the same for them. Our results provide a new insight into the origin of the GPs in pulsars.
The use of cryogenic coolant in metal cutting has received renewed recent attention because liquid nitrogen is a safe, clean, non-toxic coolant that requires no expensive disposal and can ...substantially improve tool life. This work investigates the effectiveness of cryogenic coolant during turning of Ti-6Al-4V at a constant speed and material removal rate (125
m/min, 48.5
cm
3/min) with different combinations of feed rate and depth of cut. It is found that the greatest improvement in tool life using cryogenic coolant occurs for conditions of high feed rate and low depth of cut combinations. However, this combination of machining parameters produces much shorter tool life compared to low feed rate and high depth of cut combinations. It is found that preventing heat generation during cutting is far more advantageous towards extending tool life rather than attempting to remove the heat with cryogenic coolant. Although cryogenic coolant is effective in extracting heat from the cutting zone, it is proposed that cryogenic coolant may limit the frictional heat generated during cutting and limit heat transfer to the tool by reducing the tool–chip contact length. The effect of cryogenic coolant on cutting forces and chip morphology is also examined.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Social development and technological advancement have led to land use changes, influencing the structure of ecosystem services and severely impacting ecological balance. This study spatially and ...quantitatively assesses the effects of land‐use changes on ecosystem services based on the fourth assessment report of the Intergovernmental Panel on Climate Change (IPCC) and using the Integrated Valuation of Ecosystem Services and Tradeoff (InVEST) model. This model, applied on a global scale, was used to quantify the changes in three ecosystem services, namely, carbon storage, water yield, and sediment retention, 2010 and 2100 under four land use scenarios (A1B, A2, B1, and B2) and to evaluate the impact of land use changes to these services. The results indicate that (1) sediment retention and carbon storage under scenario B1 increase more than under other scenarios, with average global increases of 175.74 t/km2 and 913.60 Mg/km2, respectively; water yield increase only under scenario A2 between 2010 and 2100, with average global increase of 3.51 mm; (2) forest and grassland are the principal land types providing three ecosystem services globally, and decreasing the area of barren contributes to increases in three ecosystem services; and (3) when barren is converted to forest, grassland, cropland, and urban, ecosystem services all increase, strengthening the utilization of barren land can increase ecosystem services greatly. This study provides a reference for further research and the sustainable development of ecosystem services.
Plain Language Summary
Analyzing the effects of land use changes on ecosystem services on a global scale is vital for the promotion of the sustainable development of ecosystems, especially in little‐studied areas. Many studies have mapped and analyzed ecosystem services, but most have considered only local regions. There is no global research on this subject using IPCC SRES scenarios. This study aims to predict how different development scenarios (A1B, A2, B1, and B2) affect land use changes and to analyze the impact of corresponding land use changes on the ecosystem services of carbon storage, water yield, and sediment retention from a global perspective. We found that sediment retention and carbon storage under scenario B1 increased more than under other scenarios, with average global increases of 175.74 t/km2 and 913.60 Mg/km2, respectively; water yield increased only under scenario A2 between 2010 and 2100, with average global increase of 3.51 mm, when forest, grassland, cropland, and urban were converted to barren, all three ecosystem services increased, strengthening the utilization of barren land increased ecosystem services greatly.
Key Points
This research assesses the impact of future global land‐use changes on carbon storage, water yield, and sediment retention
Forest and grassland are the principal land types providing three ecosystem services globally
Strengthening the utilization of barren land can increase ecosystem services greatly
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A novel temporal contrast filter (TCF)-based method was developed to detect supersonic small infrared targets. The proposed hysteresis threshold-based detection followed by the TCF can enhance the ...accuracy of the target position, the robustness to background clutter and the velocity range of moving targets compared with the conventional temporal variance filter-based method.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The Achilles’ heel of additively manufactured Ti-6Al-4V by selective laser melting (SLM) is its inferior mechanical properties compared with its wrought (forged) counterparts. Acicular
α
′ martensite ...resulted from rapid cooling by SLM is primarily responsible for high strength but inadequate tensile ductility achieved in the as-fabricated state. This study presents a solution to eliminating the adverse effect of the nonequilibrium
α
′ martensite. This is achieved by enabling in situ martensite decomposition into a novel ultrafine (200–300 nm) lamellar (
α
+
β
) microstructure via the selection of an array of processing variables including the layer thickness, energy density, and focal offset distance. The resulting tensile elongation reached 11.4% while the yield strength was kept above 1100 MPa. These properties compare favorably with those of mill-annealed Ti-6Al-4V consisting of globular
α
and
β
. The fatigue life of SLM-fabricated Ti-6Al-4V with an ultrafine lamellar (
α
+
β
) structure has approached that of the mill-annealed counterparts and is much superior to that of SLM-fabricated Ti-6Al-4V with
α
′ martensite.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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