Developing long bones respond to surrounding tissues by trans-pairing of periosteal osteoclasts and endocortical osteoblasts.

Developing long bones alter their shape while maintaining uniform cortical thickness via coordinated activity of bone-forming osteoblasts and bone-resorbing osteoclasts at periosteal and endosteal surfaces, a process we designate trans-pairing. Two types of trans-pairing shift cortical bone in opposite orientations: peri-forming trans-pairing (peri-t-p) increases bone marrow space and endo-forming trans-pairing (endo-t-p) decreases it, via paired activity of bone resorption and formation across the cortex. Here, we focused on endo-t-p in growing bones. Analysis of endo-t-p activity in the cortex of mouse fibulae revealed osteoclasts under the periosteum compressed by muscles, and expression of RANKL in periosteal cells of the cambium layer. Furthermore, mature osteoblasts were localized on the endosteum, while preosteoblasts were at the periosteum and within cortical canals. X-ray tomographic microscopy revealed the presence of cortical canals more closely associated with endo- than with peri-t-p. Sciatic nerve transection followed by muscle atrophy and unloading induced circumferential endo-t-p with concomitant spread of cortical canals. Such canals likely supply the endosteum with preosteoblasts from the periosteum under endo-t-p, allowing bone shape to change in response to mechanical stress or nerve injury.

Sitting knee-flexion angle does not influence endothelial-dependent vasodilation in laboratory or free-living conditions.

INTRODUCTION: Single bouts of prolonged bent-legged sitting attenuate popliteal endothelial-dependent vasodilation (as assessed via flow-mediated dilation [FMD]), which is partially attributed to arterial 'kinking'. However, the impact of knee-flexion angle on sitting-induced popliteal FMD is unknown. The objective of this study was to perform separate laboratory and free-living studies to test the hypotheses that: (1) popliteal FMD impairments would be graded between knee flexions at 90° (bent-legged sitting) > 45° > 0° (straight-legged sitting) following a 3-hour bout of sitting; and (2) more habitual time spent bent-legged sitting (< 45°) would be associated with lower FMD. METHODS: The laboratory study included eight young, healthy adults (24 ± 2 years; four women) who underwent two sitting bouts over 2 days with one leg positioned at a knee-flexion angle of 0° or 90° and the opposite leg at 45° knee flexion. Popliteal FMD was assessed at pre- and postsitting timepoints. RESULTS: Sitting-induced reductions in FMD were similar between all knee-flexion angles (all, p > 0.674). The free-living study included 35 young, healthy adults (23 ± 3 years; 16 women) who wore three activPAL monitors (torso, thigh, shin) to determine detailed sedentary postures. Time spent sedentary (624 ± 127 min/day), straight-legged sitting (112 ± 98 min/day), and bent-legged sitting (442 ± 106 min/day) were not related to relative FMD (5.3 ± 1.8%; all, p > 0.240). CONCLUSION: These findings suggest that knee-flexion angle-mediated arterial 'kinking' during sitting is not a major contributor toward sitting-induced popliteal endothelial-dependent vasodilatory dysfunction.

Assessment of relationships between frailty and chronic pain: a bidirectional two-sample Mendelian randomisation study.

BACKGROUND: Previous observational studies have indicated a complex association between chronic pain and frailty. This study aimed to examine the bidirectional causal relationship between frailty and chronic pain and to quantify mediating effects of known modifiable risk factors. METHODS: A bidirectional two-sample Mendelian randomisation (MR) analysis was applied in this study. Summary genome-wide association statistics for frailty, as defined by both frailty index (FI) and Fried Frailty Score (FFS), pain at seven site-specific chronic pain (SSCP) (headache, facial, neck/shoulder, stomach/abdominal, back, hip and knee) and multisite chronic pain (MCP) were extracted from populations of European ancestry. Genetic instrumental variables strongly correlated with each exposure were selected. The inverse-variance-weighted method was the primary method used in the MR, supplemented by a range of sensitivity and validation analyses. Two-step MR analysis was undertaken to evaluate the mediating effects of several proposed confounders. RESULTS: Genetically predicted higher FI and FFS were associated with an increased risk of MCP and specific types of SSCP, including neck/shoulder pain, stomach/abdominal pain, back pain, hip pain and knee pain. In the reverse direction analysis, genetic liability to MCP was found to be associated with increased FI and FFS. These results remained consistent across sensitivity and validation assessments. Two-step MR suggested a mediating role for body mass index, smoking initiation, physical inactivity, educational attainment and depression. CONCLUSIONS: Our research provided genetic evidence that the association between frailty and chronic pain was bidirectional where the coexistence of both conditions will exacerbate each other.

Two-lung ventilation with artificial pneumothorax on cerebral desaturation and early postoperative cognitive outcome: a randomized controlled trial.

BACKGROUND: The effect of two lung ventilation (TLV) with carbon dioxide artificial pneumothorax on cerebral desaturation and postoperative neurocognitive changes in elderly patients undergoing elective minimally invasive esophagectomy (MIE) is unclear. OBJECTIVES: The first aim of this study was to compare the effect of TLV and one lung ventilation (OLV) on cerebral desaturation. The second aim was to assess changes in early postoperative cognitive outcomes of two ventilation methods. METHODS: This prospective, randomized, controlled trial enrolled patients 65 and older scheduled for MIE. Patients were randomly assigned (1:1) to TLV group or OLV group. The primary outcome was the incidence of cerebral desaturation events (CDE). Secondary outcomes were the cumulative area under the curve of desaturation for decreases in regional cerebral oxygen saturation (rSO2) values below 20% relative to the baseline value (AUC.20) and the incidence of delayed neurocognitive recovery. RESULTS: Fifty-six patients were recruited between November 2019 and August 2020. TLV group had a lower incidence of CDE than OLV group [3 (10.71%) vs. 13 (48.14%), P = 0.002]. TLV group had a lower AUC.20 [0 (0-35.86) % min vs. 0 (0-0) % min, P = 0.007], and the incidence of delayed neurocognitive recovery [2 (7.4%) vs. 11 (40.7%), P = 0.009] than OLV group. Predictors of delayed neurocognitive recovery on postoperative day 7 were age (OR 1.676, 95% CI 1.122 to 2.505, P = 0.006) and AUC.20 (OR 1.059, 95% CI 1.025 to 1.094, P < 0.001). CONCLUSION: Compared to OLV, TLV had a lower incidence of CDE and delayed neurocognitive recovery in elderly patients undergoing MIE. The method of TLV combined with carbon dioxide artificial pneumothorax may be an option for these elderly patients. Chinese Clinical Trial Registry (identifier: ChiCTR1900027454).

Cold exposure-induced plasma exosomes impair bone mass by inhibiting autophagy.

Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.

Effects of transcranial direct current stimulation on pain and physical function in patients with knee osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Keen Osteoarthritis (KOA) is a common chronic disabling disease characterized by joint pain and dysfunction, which seriously affects patients' quality of life. Recent studies have shown that transcranial direct current stimulation (tDCS) was a promising treatment for KOA. PURPOSE: Investigate the effects of tDCS on pain and physical function in patients with KOA. METHODS: Randomized controlled trials related to tDCS and KOA were systematically searched in the PubMed, Embase, Medline, Cochrane Library, CINHL, and Web of Science databases from inception to July 23, 2024. The pain intensity was evaluated using the visual analog scale or the numeric rating scale, and the pain sensitivity was assessed using conditioned pain modulation, pressure pain threshold, heat pain threshold, or heat pain tolerance. The physical function outcome was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index or the Knee injury and Osteoarthritis Outcome Score. Statistical analysis was performed using Review Manager 5.4. RESULTS: Seven studies with a total of 503 participants were included. Compared to sham tDCS, tDCS was effective in reducing the short-term pain intensity (SMD: -0.58; 95% CI: -1.02, -0.14; p = 0.01) and pain sensitivity (SMD: -0.43; 95% CI: -0.70, -0.16; p = 0.002) but failed to significantly improve the long-term pain intensity (SMD: -0.26; 95% CI: -0.59, 0.08; p = 0.13) in KOA patients. In addition, tDCS did not significantly improve the short-term (SMD: -0.13; 95% CI: -0.35, 0.08; p = 0.22) and long-term (SMD: 0.02; 95% CI: -0.22, 0.25; p = 0.90) physical function in patients with KOA. CONCLUSIONS: The tDCS can reduce short-term pain intensity and sensitivity but fails to significantly relieve long-term pain intensity and improve the physical function in patients with KOA. Thus, tDCS may be a potential therapeutic tool to reduce short-term pain intensity and pain sensitivity in patients with KOA.

Risk/benefit trade-off of habitual physical activity and air pollution on mortality: A large-scale prospective analysis in the UK Biobank.

BACKGROUND: Previous observational studies have indicated associations of physical activity (PA) and air pollution with mortality. A few studies have evaluated air pollution and PA interactions for health. Still, the trade-off between the harmful effects of air pollution exposure and the protective effects of PA remains controversial and unclear. OBJECTIVE: This study aimed to investigate the joint association of air pollution and PA with mortality risks. METHODS: This prospective cohort study included 322,092 participants from 2006 to 2010 and followed up to 2021 in the UK Biobank study. The concentrations of air pollutants (2006-2010), including particulate matter (PM) with diameters <=2.5 mm (PM2.5), <=10 mm (PM10), and between 2.5 and 10 mm (PM2.5-10), and nitrogen oxides (NO2 and NOx) were obtained. Information on PA measured by the International Physical Activity Questionnaire short form (2006-2010) and wrist-worn accelerometer (2013-2015) were collected. All-cause and cause-specific mortalities were recorded. Cox proportional hazard models were used to investigate the associations of air pollution exposure and PA with mortality risks. The additive and multiplicative interactions were also examined. RESULTS: During a mean follow-up of 11.83 years, 16629 deaths were recorded. Compared with participants reporting low PA, higher PA was negatively associated with all-cause [hazard ratio (HR), 0.74; 95% CI, 0.71-0.78], cancer (HR, 0.85; 95% CI, 0.80-0.90), CVD (HR, 0.79; 95% CI, 0.71-0.87), and respiratory disease-specific mortality (HR, 0.51; 95% CI, 0.44-0.60). Exposure to PM2.5 (HR, 1.05; 95% CI, 1.00-1.09) and NOx (HR, 1.06; 95% CI, 1.02-1.10) was connected with increased all-cause mortality risk, and significant PM2.5-associated elevated risks for CVD mortality and NOx-associated elevated risks for respiratory disease mortality were observed. No obvious interaction between PA and PM2.5 or NOx exposure was detected. CONCLUSIONS: Our study provides additional evidence that higher PA and lower air pollutant levels are independently connected with reduced mortality risk. The benefits of PA are not significantly affected by long-term air pollution exposure, indicating PA can be recommended to prevent mortality regardless of air pollution levels. Our findings highlight the importance of public health policies and interventions facilitating PA and reducing air pollution in reducing mortality risks and maximizing health benefits. Future investigation is urgently needed to identify these findings in areas with severe air pollution conditions.

Relationships between bilateral auditory brainstem activity and inter-implant interval in children with cochlear implants.

PURPOSE: To investigate the effect of the interval between bilateral cochlear implantation on the development of bilateral peripheral auditory pathways as revealed by the electrically evoked auditory brainstem response (EABR). METHODS: Fifty-eight children with profound bilateral sensorineural hearing loss were recruited. Among them, 33 children received sequential bilateral cochlear implants (CIs), and 25 children received simultaneous bilateral CIs. The bilateral EABRs evoked by electrical stimulation from the CI electrode were recorded on the day of second-side CI activation. RESULTS: The latencies of wave III (eIII) and wave V (eV) were significantly shorter on the first CI side than on the second CI side in children with sequential bilateral CIs but were similar between the two sides in children with simultaneous bilateral CIs. Furthermore, the latencies were prolonged from apical to basal channels along the cochlea in the two groups. In children with sequential CIs, the inter-implant interval was negatively correlated with the eV latency on the first CI side and was positively correlated with bilateral differences in the eIII and eV latencies. CONCLUSIONS: Unilateral CI use promotes the maturation of ipsilateral auditory conduction function. However, a longer inter-implant interval results in more unbalanced development of bilateral auditory brainstem pathways. Bilateral cochlear implantation with no or a short interval is recommended.

Cold exposure protects against medial arterial calcification development via autophagy.

Medial arterial calcification (MAC), a systemic vascular disease different from atherosclerosis, is associated with an increased incidence of cardiovascular events. Several studies have demonstrated that ambient temperature is one of the most important factors affecting cardiovascular events. However, there has been limited research on the effect of different ambient temperatures on MAC. In the present study, we showed that cold temperature exposure (CT) in mice slowed down the formation of vitamin D (VD)-induced vascular calcification compared with room temperature exposure (RT). To investigate the mechanism involved, we isolated plasma-derived exosomes from mice subjected to CT or RT for 30 days (CT-Exo or RT-Exo, respectively). Compared with RT-Exo, CT-Exo remarkably alleviated the calcification/senescence formation of vascular smooth muscle cells (VSMCs) and promoted autophagy by activating the phosphorylation of AMP-activated protein kinase (p-AMPK) and inhibiting phosphorylation of mammalian target of rapamycin (p-mTOR). At the same time, CT-Exo promoted autophagy in ß-glycerophosphate (ß-GP)-induced VSMCs. The number of autophagosomes and the expression of autophagy-related proteins ATG5 and LC3B increased, while the expression of p62 decreased. Based on a microRNA chip microarray assay and real-time polymerase chain reaction, miR-320a-3p was highly enriched in CT-Exo as well as thoracic aortic vessels in CT mice. miR-320a-3p downregulation in CT-Exo using AntagomiR-320a-3p inhibited autophagy and blunted its anti-calcification protective effect on VSMCs. Moreover, we identified that programmed cell death 4 (PDCD4) is a target of miR-320a-3p, and silencing PDCD4 increased autophagy and decreased calcification in VSMCs. Treatment with CT-Exo alleviated the formation of MAC in VD-treated mice, while these effects were partially reversed by GW4869. Furthermore, the anti-arterial calcification protective effects of CT-Exo were largely abolished by AntagomiR-320a-3p in VD-induced mice. In summary, we have highlighted that prolonged cold may be a good way to reduce the incidence of MAC. Specifically, miR-320a-3p from CT-Exo could protect against the initiation and progression of MAC via the AMPK/mTOR autophagy pathway.

Characterization of Detailed Sedentary Postures Using a Tri-Monitor ActivPAL Configuration in Free-Living Conditions.

Objective monitors such as the activPAL characterize time when the thigh is horizontal as sedentary time. However, there are physiological differences between lying, bent-legged sitting, and straight-legged sitting. We introduce a three-monitor configuration to assess detailed sedentary postures and demonstrate its use in characterizing such positions in free-living conditions. We explored time spent in each sedentary posture between prolonged (>1 h) versus non-prolonged (<1 h) sedentary bouts. In total, 35 healthy adults (16♀, 24 ± 3 years; 24 h/day for 6.8 ± 1.0 days) wore an activPAL accelerometer on their thigh, torso, and shin. Hip and knee joint flexion angle estimates were determined during sedentary bouts using the dot-product method between the torso−thigh and thigh−shin, respectively. Compared to lying (69 ± 60 min/day) or straight-legged sitting (113 ± 100 min/day), most time was spent in bent-legged sitting (439 ± 101 min/day, p < 0.001). Most of the bent-legged sitting time was accumulated in non-prolonged bouts (328 ± 83 vs. 112 ± 63 min/day, p < 0.001). In contrast, similar time was spent in straight-legged sitting and lying between prolonged/non-prolonged bouts (both, p > 0.26). We document that a considerable amount of waking time is accumulated in lying or straight-legged sitting. This methodological approach equips researchers with a means of characterizing detailed sedentary postures in uncontrolled conditions and may help answer novel research questions on sedentariness.

Mesenchymal stem cell-derived exosomes in cancer therapy resistance: recent advances and therapeutic potential.

Mesenchymal stem cells (MSCs) are multipotent stromal cells that can be obtained from various human tissues and organs. They can differentiate into a wide range of cell types, including osteoblasts, adipocytes and chondrocytes, thus exhibiting great potential in regenerative medicine. Numerous studies have indicated that MSCs play critical roles in cancer biology. The crosstalk between tumour cells and MSCs has been found to regulate many tumour behaviours, such as proliferation, metastasis and epithelial-mesenchymal transition (EMT). Multiple lines of evidence have demonstrated that MSCs can secrete exosomes that can modulate the tumour microenvironment and play important roles in tumour development. Notably, very recent works have shown that mesenchymal stem cell-derived exosomes (MSC-derived exosomes) are critically involved in cancer resistance to chemotherapy agents, targeted-therapy drugs, radiotherapy and immunotherapy. In this review, we systematically summarized the emerging roles and detailed molecular mechanisms of MSC-derived exosomes in mediating cancer therapy resistance, thus providing novel insights into the clinical applications of MSC-derived exosomes in cancer management.

What is the impact of aerobic fitness and movement interventions on low-flow-mediated vasoconstriction? A systematic review of observational and intervention studies.

The cardiovascular benefits of physical exercise are well established. The vasoreactivity that occurs during reductions in local arterial blood flow, termed low-flow-mediated constriction (L-FMC), is a measure of endothelial-dependent vasoconstrictor function. It is unclear whether aerobic fitness and movement (or lack thereof) influences L-FMC. We systematically reviewed studies examining the impact of physical behaviours on L-FMC. To be included, cross-sectional and interventional studies had to examine the impact of a physical behaviour on L-FMC in adults. There were no language or date of publication restrictions. Sources were searched in May, 2021 and included Scopus, Embase, MEDLINE, CINAHL, and Academic Search Premier. National Institutes of Health quality assessment tools were used. Fourteen studies (15 arms; 313 participants; 398 total observations from four arteries) met the inclusion criteria. The study quality varied from four out of 14 (controlled intervention scoring) to nine out of 12 (longitudinal intervention with no control group scoring) with the total points dependent upon the study design. Conflicting results were reported for acute prolonged sitting studies (attenuated L-FMC: n = 1; no change: n = 1) and resistance exercise (increased L-FMC: n = 2; no change: n = 2). Most observational studies examining aerobic fitness (3/4 studies) and aerobic exercise interventions (4/5 studies) observed a favourable effect on L-FMC. Overall, the included studies support that higher aerobic fitness and engaging in aerobic exercise training may augment L-FMC responses. Our systematic review highlights the heterogeneity between studies and identifies current gaps and future directions to better our understanding of (in)activity, exercise, and posture on endothelial vasoconstrictor function. PROSPERO Registration No.: CRD42021248241.

Impact of habitual sedentary patterns on popliteal artery endothelial-dependent vasodilation in healthy adults.

INTRODUCTION: Acute, laboratory-based bouts of prolonged sitting attenuate lower-limb arterial endothelial-dependent vasodilation. However, the impact of habitual sedentary patterns on popliteal artery endothelial health is unclear. We tested the hypothesis that greater habitual total sedentary time, more time spent in prolonged sedentary bouts, and fewer sedentary breaks would be associated with worse popliteal flow-mediated dilation (FMD) responses. METHODS: This cross-sectional study used 98 healthy participants (19-77 years, 53 females) that wore an activPAL monitor on the thigh for 6.4 ± 0.8 days to objectively measure sedentary activity and completed a popliteal ultrasound assessment to determine FMD. Both relative (%baseline diameter) and absolute (mm) FMD were calculated. Using bivariate correlation and multiple regression analyses, we examined if there were relationships between sedentary outcomes and FMD while statistically controlling for any potential confounders. RESULTS: In the multiple regression model, age (p = 0.006, ß = -0.030, 95% CI = -0.051, -0.009) and total time in sedentary bouts > 1 hour (p = 0.031, ß = -0.005, 95% CI = -0.009, -0.001) were independent predictors of relative FMD. Age (ß = -0.002, 95% CI = -0.003, -0.001), mean blood flow (ß = 0.013, 95% CI = 0.002, 0.024), moderate-intensity physical activity (ß = 155.9E-5, 95% CI = 22.4E-5, 289.4E-5), sedentary breaks (ß = 0.036, 95% CI = 0.007, 0.066), and total time spent in sedentary bouts > 1 hour (ß = -25.02E-5, 95% CI = -47.67E-5, -2.378E-5) were predictors of absolute FMD (all, p < 0.047). All independent outcomes remained significant after partially controlling for all other predictor variables (all, p < 0.031). CONCLUSIONS: Habitual prolonged sedentary bouts and sedentary breaks, but not total sedentary time, were predictors of popliteal endothelial-dependent vasodilatory function. The patterns by which sedentary time is accumulated may be more important than the total sedentary time on lower-limb arterial health.

[Lung parenchyma segmentation based on double scale parallel attention network].

[Abstract]Automatic and accurate segmentation of lung parenchyma is essential for assisted diagnosis of lung cancer. In recent years, researchers in the field of deep learning have proposed a number of improved lung parenchyma segmentation methods based on U-Net. However, the existing segmentation methods ignore the complementary fusion of semantic information in the feature map between different layers and fail to distinguish the importance of different spaces and channels in the feature map. To solve this problem, this paper proposes the double scale parallel attention (DSPA) network (DSPA-Net) architecture, and introduces the DSPA module and the atrous spatial pyramid pooling (ASPP) module in the "encoder-decoder" structure. Among them, the DSPA module aggregates the semantic information of feature maps of different levels while obtaining accurate space and channel information of feature map with the help of cooperative attention (CA). The ASPP module uses multiple parallel convolution kernels with different void rates to obtain feature maps containing multi-scale information under different receptive fields. The two modules address multi-scale information processing in feature maps of different levels and in feature maps of the same level, respectively. We conducted experimental verification on the Kaggle competition dataset. The experimental results prove that the network architecture has obvious advantages compared with the current mainstream segmentation network. The values of dice similarity coefficient (DSC) and intersection on union (IoU) reached 0.972 ± 0.002 and 0.945 ± 0.004, respectively. This paper achieves automatic and accurate segmentation of lung parenchyma and provides a reference for the application of attentional mechanisms and multi-scale information in the field of lung parenchyma segmentation.

Staircase array of inclined refractive multi-lenses for large field of view pixel super-resolution scanning transmission hard X-ray microscopy.

Owing to the development of X-ray focusing optics during the past decades, synchrotron-based X-ray microscopy techniques allow the study of specimens with unprecedented spatial resolution, down to 10 nm, using soft and medium X-ray photon energies, though at the expense of the field of view (FOV). One of the approaches to increase the FOV to square millimetres is raster-scanning of the specimen using a single nanoprobe; however, this results in a long data acquisition time. This work employs an array of inclined biconcave parabolic refractive multi-lenses (RMLs), fabricated by deep X-ray lithography and electroplating to generate a large number of long X-ray foci. Since the FOV is limited by the pattern height if a single RML is used by impinging X-rays parallel to the substrate, many RMLs at regular intervals in the orthogonal direction were fabricated by tilted exposure. By inclining the substrate correspondingly to the tilted exposure, 378000 X-ray line foci were generated with a length in the centimetre range and constant intervals in the sub-micrometre range. The capability of this new X-ray focusing device was first confirmed using ray-tracing simulations and then using synchrotron radiation at BL20B2 of SPring-8, Japan. Taking account of the fact that the refractive lens is effective for focusing high-energy X-rays, the experiment was performed with 35 keV X-rays. Next, by scanning a specimen through the line foci, this device was used to perform large FOV pixel super-resolution scanning transmission hard X-ray microscopy (PSR-STHXM) with a 780 ± 40 nm spatial resolution within an FOV of 1.64 cm × 1.64 cm (limited by the detector area) and a total scanning time of 4 min. Biomedical implant abutments fabricated via selective laser melting using Ti-6Al-4V medical alloy were measured by PSR-STHXM, suggesting its unique potential for studying extended and thick specimens. Although the super-resolution function was realized in one dimension in this study, it can be expanded to two dimensions by aligning a pair of presented devices orthogonally.

miR-21 inhibition reverses doxorubicin-resistance and inhibits PC3 human prostate cancer cells proliferation.

Many approaches have been examined to reversing multidrug resistance (MDR), but sub-optimal target-based strategies have limited their efficacy. Herein, we investigate microRNA (miR-21) suppression on the doxorubicin (DOX)-sensitisation of the DOX-resistant (PC3/DOX) cell line in prostate cancer (PCa). Expression levels of miR-21, P-glycoprotein (P-gp), MDR-1 and PTEN evaluated in PC3/DOX cancer cells by qRT-PCR and western blot analyses. The cytotoxic effects of transfected of miR-21 were assessed by MTT assay for 72 hr. Rhodamine123 (Rh123) assay was employed to define the activity of P-gp. Apoptosis was detected by Flow cytometry. As expected, miR-21 was expressed highly in PC3/DOX cells (p < 0.05). It was shown that miRNA-21 suppression considerably hindered PC3/DOX cell viability. miR-21 suppression dramatically downregulated P-gp expression and activity in DOX-resistance cells and abolished MDR by an increment of intracellular accumulation of DOX in PC3/DOX cells (p < 0.05). PTEN is a key modulator of the PI3K/Akt/P-gp cascade, which miR-21 suppression led to the upregulation of PTEN and sequentially lower-expression of P-gp that reversed MDR. Also, miR-21 repression enhanced the apoptosis rate of PC3/DOX cells. The findings of this paper contribute to the current understanding of the functions of miR-21 in MDR-reversing in PCa.

Improving the criterion validity of the activPAL in determining physical activity intensity during laboratory and free-living conditions.

The activPAL is a valid measure of step counts and posture, but its ability to determine physical activity intensity is unclear. This study tested the criterion validity of the activPAL using its built-in linear cadence-metabolic equivalents (METs) equation (activPAL-linear) versus an individualized height-adjusted curvilinear cadence-METs equation (activPAL-curvilinear) to estimate intensity-related physical activity. Forty adults (25±6 years, 23.3±4.1 kg/m2) wore an activPAL during a 7-stage progressive treadmill walking protocol (criterion: indirect calorimetry). A sub-sample (n=32) wore the device during free-living conditions for 7-days (criterion: PiezoRxD monitor). In the laboratory, the activPAL-linear overestimated METs during slow walking (1.5-3.0 miles•hour-1) but underestimated METs during fast walking (3.5-4.5 miles•hour-1) (all, p<0.001). In the free-living condition, the activPAL-linear overestimated time in light-intensity activity and underestimated moderate-intensity activity (both, p<0.001), but did not register any vigorous-intensity activity. In contrast, the activPAL-curvilinear estimated values statistically equivalent to indirect calorimetry for treadmill stages 1-6 (1.5-4.0 miles•hour-1) and to the PiezoRxD determined light- and moderate-intensity activity during free-living. We present a simple, data processing technique that uses an alternative curvilinear cadence-MET equation that improves the ability of the activPAL to measure intensity-related physical activity in both laboratory and free-living settings.

Intravitreal ranibizumab or conbercept for retinal arterial macroaneurysm: a case series.

BACKGROUND: There is no consensus for the standard treatment of retinal arterial macroaneurysm (RAM). Intravitreal anti-vascular endothelium growth factor (anti-VEGF) is an alternative treatment option for RAM. The purpose of this study is to describe the clinical efficacy of intravitreal ranibizumab or intravitreal conbercept for retinal arterial macroaneurysm. CASE PRESENTATION: Three cases that presented with symptomatic RAM were treated with intravitreal anti-VEGF agents. Two eyes received two intravitreal ranibizumab injections with a time interval of one month and completed a one-year follow-up, while one eye only received one intravitreal conbercept injection and was followed up for six months. Both the retinal thickness and the visual acuity were significantly improved at the final clinic visit. The macular hemorrhage and edema were resolved. There were no ocular or systemic side effects. CONCLUSIONS: Intravitreal ranibizumab or conbercept might be used as a therapeutic option for symptomatic retinal arterial macroaneurysm patients. Anti-VEGF therapy should be further investigated in a larger series with longer follow-up for this disease profile.

MiR-539 inhibits proliferation and migration of triple-negative breast cancer cells by down-regulating LAMA4 expression.

BACKGROUND: Recent studies have shown that laminin subunit alpha 4 (LAMA4) plays an important role in carcinogenesis. However, its molecular biological function in triple-negative breast cancer (TNBC) has not been entirely clarified. This study investigated the expression of LAMA4 in TNBC and its effect on cell proliferation, migration and invasion. Furthermore, we also identified the potential miRNA directly targeting LAMA4. METHODS: Western blot, Real-time quantitative PCR (qPCR) and immunohistochemical staining (IHC) were used to detect the expression of LAMA4 in TNBC. The effects of LAMA4 on TNBC cell proliferation, migration and invasion were also explored in vitro. The potential miRNA that targets LAMA4 was determined by dual luciferase reporter assay and verified by qPCR and western blot analysis. RESULTS: Our study showed LAMA4 mRNA (p = 0.001) and protein (p = 0.005) expression in TNBC tissue samples were elevated compared with adjacent normal tissue samples, and LAMA4 was mainly expressed in the cytoplasm of breast carcinoma cells. Knockdown of LAMA4 inhibited TNBC cell proliferation, migration and invasion in vitro. Moreover, further study revealed that LAMA4 was a putative target of miR-539, and miR-539 negatively regulated LAMA4 expression by directly targeting its 3'-UTR. CONCLUSIONS: Our study suggested that miR-539 suppressed the expression of LAMA4. LAMA4 plays an important role in tumor progression and may be an important target in treatment of TNBC.