Comparison of cement-augmented pedicle screw and conventional pedicle screw for the treatment of lumbar degenerative patients with osteoporosis.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To compare the safety and clinical efficacy between using cement-augmented pedicle screws (CAPS) and conventional pedicle screws (CPS) for the treatment of lumbar degenerative patients with osteoporosis. Management of lumbar degenerative patients with osteoporosis undergoing spine surgery is challenging. The clinical efficacy and potential complications of the mid-term performance of the CAPS technique in the treatment of lumbar degenerative patients with osteoporosis remain to be evaluated. PATIENTS AND METHODS: The data of 131 lumbar degenerative patients with osteoporosis who were treated with screw fixation from May 2016 to December 2019 were retrospectively analyzed in this study. The patients were divided into the following two groups according to the type of screw used: (I) the CAPS group (n = 85); and (II) the CPS group (n = 46). Relevant data were compared between two groups, including the demographics data, clinical results and complications. RESULTS: The difference in the VAS, ODI and JOA scores at three and 6 months after the operation between the two groups was statistically significant (P < 0.05). At 12 months after surgery and the final follow-up, a significant difference in the fusion rate was found between the two groups (P < 0.05). Four cemented screws loosening were observed in the CAPS group (loosening rate 4/384, 1.04%) and 15 screws loosening were observed in the CPS group (loosening rate 15/214, 7.01%). In the CAPS group, a total of 384 augmented screws were used, and cement leakage was observed in 25 screws (25/384, 6.51%), but no obvious clinical symptoms or serious complications were observed. Adjacent vertebral fractures occurred in six patients in the CAPS group and one in the CPS group. CONCLUSIONS: CAPS technique is an effective strategy for the treatment of lumbar degenerative patients with osteoporosis, with a higher fusion rate and lower screw loosening rate than CPS.

Single-port robot-assisted perineal radical prostatectomy with the da Vinci XI system: initial experience and learning curve using the cumulative sum method.

BACKGROUND: To evaluate the early functional and oncological outcomes of single-port robot-assisted perineal radical prostatectomy (sp-pRARP) using the da Vinci XI system and analyze its learning curve using the cumulative sum (CUSUM) method. METHODS: The clinical data of 50 patients who underwent sp-pRARP for localized prostate cancer between May 2020 and May 2022 in our center by a single surgeon were analyzed retrospectively. Demographic information, preoperative and postoperative variables, complications, early functional and oncological outcomes of patients were recorded. The CUSUM method was used to illustrate the learning curve based on operation time. RESULTS: All surgeries were completed without conversion. The median (interquartile range, IQR) operation time was 205.0 (82.5) min, whereas the median (IQR) docking time was 30.0 (15.0) min and the console time was 120.0 (80.5) min. The median (IQR) estimated blood loss (EBL) was 50.0 (137.5) mL. Positive surgical margins were detected in five patients (10.0%). The continence rate was 40.9%, 63.6%, 88.4%, and 97.7% at the 1, 3, 6, and 12 months after surgery. According to the CUSUM plot, the inflection points of the learning curve were 20 cases, splitting the case series into "early phase" and "late phase." In "late phase" cases, there was less time spent on each step of the operation and less EBL. CONCLUSIONS: Sp-pRARP using the da Vinci XI system was verified to be a feasible and reliable surgical approach. According to the CUSUM plot, 20 cases was considered the turning point for surgeons to master the novel technique.

Differential Membrane Protein Profile in Bovine X- and Y-Sperm.

The aim of this study was to understand the molecular mechanisms behind the biological differences of X- and Y-sperm and to screen the sex-specific candidate antigen proteins for sexed semen production. To this end, we investigated differential expression of total membrane proteins of the two sperm types by using high-purity X- and Y-sperm from 20 Holstein bulls and applying the label-free proteomic technique; 1521 proteins were identified. In the X-sperm group, 8 and 23 proteins were significantly up- and down-regulated, respectively. In the X- and the Y-sperm group, 151 and 88 proteins were specifically expressed, respectively. These were overexpressed in the dynamic changes of the actin cytoskeleton, and cell senescence/apoptosis induced by the immune response, and could result in differences in the state, size, and immune sensitivity of the X-/Y-sperm membranes. The prediction of transmembrane structure, subcellular localization, and Western blotting validation results showed that the CLRN3 and SCAMP1 proteins were cell surface specific antigens of X- and Y-sperm, respectively. Our findings help explain the molecular mechanism behind the biological differences of X-/Y-sperm and lay the foundation for application of immunological methods to produce sex-sorted semen and control livestock sex. Data are available via ProteomeXchange with identifier PXD019435.

Association of UDP-galactose-4-epimerase with milk protein concentration in the Chinese Holstein population.

OBJECTIVE: An initial RNA-Sequencing study revealed that UDP-galactose-4-epimerase (GALE) was one of the most promising candidates for milk protein concentration in Chinese Holstein cattle. This enzyme catalyzes the interconversion of UDP-galactose and UDP-glucose, an important step in galactose catabolism. To further validate the genetic effect of GALE on milk protein traits, genetic variations were identified, and genotypes-phenotypes associations were performed. METHODS: The entire coding region and the 5'-regulatory region (5'-UTR) of GALE were re-sequenced using pooled DNA of 17 unrelated sires. Association studies for five milk production traits were performed using a mixed linear animal model with a population encompassing 1,027 Chinese Holstein cows. RESULTS: A total of three variants in GALE were identified, including two novel variants (g.2114 A>G and g.2037 G>A) in the 5'-UTR and one previously reported variant (g.3836 G>C) in an intron. All three single nucleotide polymorphisms (SNPs) were associated with milk yield (p<0.0001), fat yield (p = 0.0006 to <0.0001), protein yield (p = 0.0232 to <0.0001) and protein percentage (p<0.0001), while no significant associations were detected between the SNPs and fat percentage. A strong linkage disequilibrium (D' = 0.96 to 1.00) was observed among all three SNPs, and a 5 Kb haplotype block involving three main haplotypes with GAG, AGC, and AGG was formed. The results of haplotype association analyses were consistent with the results of single locus association analysis (p<0.0001). The phenotypic variance ratio above 3.00% was observed for milk protein yield that was explained by SNP-g.3836G >C. CONCLUSION: Overall, our findings provided new insights into the polymorphic variations in bovine GALE gene and their associations with milk protein concentration. The data indicate their potential uses for marker-assisted breeding or genetic selection schemes.

HER4 promotes cell survival and chemoresistance in osteosarcoma via interaction with NDRG1.

Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. The abilities of chemotherapy resistance are major roadblock in the successful treatment of OS. The clarification of mechanism regarding cell survival during OS chemotherapy are important. Here, we examined HER4 expression by immunohistochemistry in a large series of OS tissues, and found HER4 expression correlated with tumor characteristics and patient survival rates. HER4 knockdown by shRNA inhibited OS cell growth and tumorigenesis, and induced cell senescence and apoptosis in vitro and in vivo. We demonstrated that HER4 expression upregulated in the adverse conditions, such as serum starvation and sphere culture. Moreover, HER4 knockdown cells became more sensitive in stressful conditions such as loss of attachment, cytotoxic agents or nutrition insufficiency. Mechanism studies revealed that HER4 interacted with NDRG1, and NDRG1 overexpression could antagonize HER4 knockdown-mediated cell growth and apoptosis in stressed conditions. There was a positive correlation between HER4 and NDRG1 immunoreactivity in OS patients. Together, our present study shows that HER4 and/or NDRG1 might play a critical role for the cell survival and chemo-resistance of OS, and could be used as potential therapeutic targets in OS.

Postoperative Adjuvant Trans-Arterial Chemoembolization for Patients with Hepatocellular Carcinoma and Portal Vein Tumor Thrombus.

BACKGROUND: It remains uncertain whether patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) benefit from postoperative adjuvant trans-arterial chemoembolization (PA-TACE). METHODS: We retrospectively identified 540 patients to form the crude cohort and adopted propensity score matching analysis to assemble another cohort of 464 patients with similar baseline characteristics. Univariate and multivariate Cox analyses were performed in exploratory subgroups to identify the independent effect of PA-TACE on overall survival (OS). RESULTS: In the overall study population, univariate analysis showed PA-TACE was associated with longer OS [odds ratio (OR) = 0.55, p = 0.001], and stratified analyses indicated an interaction between PVTT types and PA-TACE on OS (p = 0.057 for interaction). After matching, all of the characteristics were well balanced between the PA-TACE and control groups (all p > 0.05). Multivariate Cox analysis validated that the protective role of PA-TACE was significant greater with the expansion of PVTT (type I, OR 0.66; type II, OR 0.33; and type III, OR 0.33, respectively, p = 0.011 for interaction). There also was evidence of treatment effect modification by PVTT type in the crude cohort (type I, OR 0.60; type II, OR 0.32; and type III, OR 0.32, respectively, p = 0.011 for interaction). CONCLUSIONS: In patients with HCC and PVTT, PA-TACE was associated with a lower risk of death, particularly, among those with PVTT involving right/left or main portal vein, after excluding patients who were unsuitable for this procedure at 1 month after surgery.

Mid-frequency MTF compensation of optical sparse aperture system.

Optical sparse aperture (OSA) can greatly improve the spatial resolution of optical system. However, because of its aperture dispersion and sparse, its mid-frequency modulation transfer function (MTF) are significantly lower than that of a single aperture system. The main focus of this paper is on the mid-frequency MTF compensation of the optical sparse aperture system. Firstly, the principle of the mid-frequency MTF decreasing and missing of optical sparse aperture are analyzed. This paper takes the filling factor as a clue. The method of processing the mid-frequency MTF decreasing with large filling factor and method of compensation mid-frequency MTF with small filling factor are given respectively. For the MTF mid-frequency decreasing, the image spatial-variant restoration method is proposed to restore the mid-frequency information in the image; for the mid-frequency MTF missing, two images obtained by two system respectively are fused to compensate the mid-frequency information in optical sparse aperture image. The feasibility of the two method are analyzed in this paper. The numerical simulation of the system and algorithm of the two cases are presented using Zemax and Matlab. The results demonstrate that by these two methods the mid-frequency MTF of OSA system can be compensated effectively.

Danhong Huayu Koufuye Prevents Diabetic Retinopathy in Streptozotocin-Induced Diabetic Rats via Antioxidation and Anti-Inflammation.

Danhong Huayu Koufuye (DHK), a traditional Chinese prescription, is used to treat central retinal vein occlusion clinically. We previously reported that DHK prevented diabetic retinopathy (DR) in rats. Moreover, we found that it protected endothelial cells from hyperglycemia-induced apoptosis through antioxidation and anti-inflammation. Here, we investigated whether antioxidative and anti-inflammatory activities of DHK contributed to its therapeutic effect on DR in streptozotocin- (STZ-) induced diabetic rats. DHK significantly blocked the breakdown of the blood-retinal barrier (BRB) and increased the thickness of the inner nuclear layer (INL), as well as suppressed the swelling of the ganglion cell layer (GCL) in diabetic retinas. DHK remarkably increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in plasma, and decreased serum level of nitric oxide (NO). Moreover, DHK markedly reduced the serum levels of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1). Furthermore, DHK significantly downregulated protein expressions of VEGF and inducible NO synthase (iNOS) and mRNA expression of ICAM-1 in retinas. These results suggest that the antioxidative and anti-inflammatory activities of DHK may be important mechanisms involved in the protective effect of DHK on DR in STZ-induced diabetic rats.

Danhong huayu koufuye prevents deep vein thrombosis through anti-inflammation in rats.

BACKGROUND: Danhong huayu koufuye (DHK) has traditionally been used clinically for a long time in China. This study was to evaluate the effect of DHK in treating deep vein thrombosis (DVT) in rats and explore its possible mechanism. METHODS: Forty-eight Sprague-Dawley rats were divided into four groups, performed with incomplete inferior vena cava ligation to induce DVT, and orally administered with DHK (3.20 mg/kg/d), warfarin (2.00 mg/kg/d), or vehicle for 7 days. The involved inferior vena cava and thrombi were collected and measured in size. The tissue specimens were performed for routine histopathologic evaluation and immunohistochemical staining with tissue factor and matrix metalloproteinases-9. Blood samples were collected for detecting coagulation function, blood cell count, and the levels of interleukin-6 and tumor necrosis factor-α. RESULTS: The treatment of DHK markedly reduced the size of thrombi by 49.26%, and the vein wall thickness by 47.86%. The recanalization rate was significant higher in the DHK-treated group than the vehicle-treated group (26.34 ± 6.53% versus 15.91 ± 3.93%, P < 0.01). Comparing to vehicle control, DHK significantly reduced neutrophils (P < 0.05) and lymphocytes (P < 0.05), serum tumor necrosis factor-α level (4.90 ± 1.14 pg/mL versus 6.60 ± 1.62 pg/mL, P < 0.01), and the expression of matrix metalloproteinases-9 and tissue factor (P < 0.05) in thrombi. CONCLUSIONS: DHK effectively prevented DVT through anti-inflammatory action in rats.

Genetic Analysis of Egg Production Traits in Luhua Chickens: Insights from a Multi-Trait Animal Model and a Genome-Wide Association Study.

Egg production plays a pivotal role in the economic viability of hens. To analyze the genetic rules of egg production, a total of 3151 Luhua chickens were selected, the egg production traits including egg weight at first laying (Start-EW), egg weight at 43 weeks (EW-43), egg number at 43 weeks (EN-43), and total egg number (EN-All) were recorded. Then, the effects of related factors on egg production traits were explored, using a multi-trait animal model for genetic parameter estimation and a genome-wide association study (GWAS). The results showed that body weight at first egg (BWFE), body weight at 43 weeks (BW-43), age at first egg (AFE), and seasons had significant effects on the egg production traits. Start-EW and EW-43 had moderate heritability of 0.30 and 0.21, while EN-43 and EN-All had low heritability of 0.13 and 0.16, respectively. Start-EW exhibited a robust positive correlation with EW-43, while Start-EW was negatively correlated with EN-43 and EN-All. Furthermore, gene ontology (GO) results indicated that Annexin A2 (ANXA2) and Frizzled family receptor 7 (FZD7) related to EW-43, Cyclin D1 (CCND1) and A2B adenosine receptor (ADORA2B) related to EN-All, and have been found to be mainly involved in metabolism and growth processes, and deserve more attention and further study. This study contributes to accelerating genetic progress in improving low heritability egg production traits in layers, especially in Luhua chickens.

A high-density 1,024-channel probe for brain-wide recordings in non-human primates.

Large-scale neural population recordings with single-cell resolution across the primate brain remain challenging. Here we introduce the Neuroscroll probe that isolates single neuronal activities simultaneously from 1,024 densely spaced channels that are flexibly distributed across the shank of the probe. The Neuroscroll probe length is easily tunable for individual probes from 10 mm to 90 mm, covering the brain size of non-human primates and humans, and the probes remain intact and functional after repeated bending deformations. The Neuroscroll probes provided reliable recordings from large neural populations with high chronic stability up to 105 weeks in rats. Recording with each Neuroscroll probe yielded hundreds of well-isolated single units simultaneously from multiple brain regions distributed across the entire depth of the rhesus macaque brain. With the thousand simultaneously recorded channels, unprecedented probe length, excellent mechanical stability and flexible recording site distribution, the Neuroscroll probes enable a wide range of new experimental paradigms in system neuroscience studies with great versatility.

Metagenomic Sequencing Revealed Differences in the Composition of Cecal Microbes in Different Breeds of Chickens.

Intestinal microorganisms are closely related to the health, development, and production performance of animals and can also provide basic information for us to fully understand and explore the germplasm characteristics and traits of local chicken breeds. In this experiment, we used five local Chinese chicken breeds as research materials; metagenomic sequencing technology was used to explore the differences in the composition of intestinal microorganisms in different breeds, and it was found that each local chicken breed had unique unigenes, of which Silkies had the most, with a total of 12,948. GO and KEGG analyses found that the biological processes most enriched by differential functional genes include genetic coding, macromolecular transport, protein synthesis, and molecular functions such as glycoprotein binding, protein hydrolysis, etc. Each breed is enriched with specific pathways, such as Anyi tile-like gray chickens, which are enriched with pathways related to disease resistance, while Gamecocks' enrichment is related to amino acid metabolism. Random Forest and LEfSe analyses revealed specific species of intestinal microorganisms in the cecum of different breeds, such as Exiguobacterium, which is associated with melanin deposition in Silkies. Therefore, we infer that gut microorganisms are closely related to the formation of chicken breed characteristics, and the results of this experiment can provide a theoretical basis for the discovery of high-quality traits and the improvement of feeding conditions in the future.

Analysis of genome and methylation changes in Chinese indigenous chickens over time provides insight into species conservation.

Conservation of natural resources is a vital and challenging task. Numerous animal genetic resources have been effectively conserved worldwide. However, the effectiveness of conservation programmes and the variation information of species have rarely been evaluated. Here, we performed whole-genome and whole-genome bisulfite sequencing of 90 Chinese indigenous chickens, which belonged to the Tibetan, Wenchang and Bian chicken breeds, and have been conserved under different conservation programmes. We observed that low genetic diversity and high DNA methylation variation occurs during ex situ in vivo conservation, while higher genetic diversity and differentiation occurs during in situ conservation. Further analyses revealed that most DNA methylation signatures are unique within ex situ in vivo conservation. Moreover, a high proportion of differentially methylated regions is found in genomic selection regions, suggesting a link between the effects of genomic variation and DNA methylation. Altogether our findings provide valuable information about genetic and DNA methylation variations during different conservation programmes, and hold practical relevance for species conservation.

Scarcity Mindset Neuro Network Decoding With Reward: A Tree-Based Model and Functional Near-Infrared Spectroscopy Study.

Resource scarcity imposes challenging demands on the human cognitive system. Insufficient resources cause the scarcity mindset to affect cognitive performance, while reward enhances cognitive function. Here, we examined how reward and scarcity simultaneously contribute to cognitive performance. Experimental manipulation to induce a polar scarcity mindset and reward conditions within participants under functional near-infrared spectroscopy (fNIRS) recording was implemented to explore the mechanism underlying the scarcity mindset and reward in terms of behavior and neurocognition. Participants showed decreased functional connectivity from the dorsolateral prefrontal cortex (DLPFC) to the ventrolateral prefrontal cortex (VLPFC) with a scarcity mindset, a region often implicated in cognitive control. Moreover, under reward conditions, the brain activation of the maximum total Hb bold signal was mainly located in the left hemisphere [channels 1, 3, and 4, left ventrolateral prefrontal cortex (L-VLPFC) and channel 6, left dorsolateral prefrontal cortex (L-DLPFC)], and there was also significant brain activation of the right dorsolateral prefrontal cortex (R-DLPFC) in the right hemisphere (channel 17). Furthermore, these data indicate the underlying neural changes of the scarcity mentality and demonstrate that brain activities may underlie reward processing. Additionally, the base-tree machine learning model was trained to detect the mechanism of reward function in the prefrontal cortex (PFC). According to SHapley Additive exPlanations (SHAP), channel 8 contributed the most important effect, as well as demonstrating a high-level interrelationship with other channels.

How to Improve the Well-Being of Youths: An Exploratory Study of the Relationships Among Coping Style, Emotion Regulation, and Subjective Well-Being Using the Random Forest Classification and Structural Equation Modeling.

The relationship between coping styles and subjective well-being (SWB) has recently received considerable empirical and theoretical attention in the scientific literature. However, the mechanisms underlying this relationship have primarily remained unclear. The present research aimed to determine whether emotion regulation mediated the relationship between coping styles and subjective well-being (SWB). Our hypothesis is based on the integration of theoretical models among 1,247 Chinese college students. The SWB questionnaire, Ways of Coping Questionnaire, and Emotion Regulation Questionnaire were used to correlate SWB, emotion regulation strategies, and coping styles, respectively. The random forest method was applied to predict life satisfaction and estimate the average variable importance to life satisfaction. The results indicated that positive coping can indirectly influence life satisfaction via cognitive reappraisal and indirectly influence expression suppression via positive affect. Negative coping can indirectly influence negative affect via expression suppression. Besides, negative coping was positively associated with both expression suppression and negative affect. Cognitive reappraisal was found to be positively associated with positive affect. The findings indicated that coping style is essential for the SWB of college students. These findings provide insight into how coping styles impact SWB and have implications for developing and assessing emotion regulation-based interventions.

Update on Nanoparticle-Based Drug Delivery System for Anti-inflammatory Treatment.

Nanobiotechnology plays an important role in drug delivery, and various kinds of nanoparticles have demonstrated new properties, which may provide opportunities in clinical treatment. Nanoparticle-mediated drug delivery systems have been used in anti-inflammatory therapies. Diseases, such as inflammatory bowel disease, rheumatoid arthritis, and osteoarthritis have been widely impacted by the pathogenesis of inflammation. Efficient delivery of anti-inflammatory drugs can reduce medical dosage and improve therapeutic effect. In this review, we discuss nanoparticles with potential anti-inflammatory activity, and we present a future perspective regarding the application of nanomedicine in inflammatory diseases.

Identification of genes involved in inbreeding depression of reproduction in Langshan chickens.

OBJECTIVE: Inbreeding depression of reproduction is a major concern in the conservation of native chicken genetic resources. Here, based on the successful development of strongly inbred (Sinb) and weakly inbred (Winb) Langshan chickens, we aimed to evaluate inbreeding effects on reproductive traits and identify candidate genes involved in inbreeding depression of reproduction in Langshan chickens. METHODS: A two-sample t-test was performed to estimate the differences in phenotypic values of reproductive traits between Sinb and Winb chicken groups. Three healthy chickens with reproductive trait values around the group mean values were selected from each of the groups. Differences in ovarian and hypothalamus transcriptomes between the two groups of chickens were analyzed by RNA sequencing (RNA-Seq). RESULTS: The Sinb chicken group showed an obvious inbreeding depression in reproduction, especially for traits of age at the first egg and egg number at 300 days (p<0.01). Furthermore, 68 and 618 differentially expressed genes (DEGs) were obtained in the hypothalamus and ovary between the two chicken groups, respectively. In the hypothalamus, DEGs were mainly enriched in the pathways related to vitamin metabolism, signal transduction and development of the reproductive system, such as the riboflavin metabolism, Wnt signaling pathway, extracellular matrix-receptor interaction and focal adhesion pathways, including stimulated by retinoic acid 6, serpin family F member 1, secreted frizzled related protein 2, Wnt family member 6, and frizzled class receptor 4 genes. In the ovary, DEGs were significantly enriched in pathways associated with basic metabolism, including amino acid metabolism, oxidative phosphorylation, and glycosaminoglycan degradation. A series of key DEGs involved in folate biosynthesis (gamma-glutamyl hydrolase, guanosine triphosphate cyclohydrolase 1), oocyte meiosis and ovarian function (cytoplasmic polyadenylation element binding protein 1, structural maintenance of chromosomes 1B, and speedy/RINGO cell cycle regulator family member A), spermatogenesis and male fertility (prostaglandin D2 synthase 21 kDa), Mov10 RISC complex RNA helicase like 1, and deuterosome assembly protein 1) were identified, and these may play important roles in inbreeding depression in reproduction. CONCLUSION: The results improve our understanding of the regulatory mechanisms underlying inbreeding depression in chicken reproduction and provide a theoretical basis for the conservation of species resources.

Anlotinib Reverses Multidrug Resistance (MDR) in Osteosarcoma by Inhibiting P-Glycoprotein (PGP1) Function In Vitro and In Vivo.

Overexpression of the multidrug resistance (MDR)-related protein P-glycoprotein (PGP1), which actively extrudes chemotherapeutic agents from cells and significantly decreases the efficacy of chemotherapy, is viewed as a major obstacle in osteosarcoma chemotherapy. Anlotinib, a novel tyrosine kinase inhibitor (TKI), has good anti-tumor effects in a variety of solid tumors. However, there are few studies on the mechanism of anlotinib reversing chemotherapy resistance in osteosarcoma. In this study, cellular assays were performed in vitro and in vivo to evaluate the MDR reversal effects of anlotinib on multidrug-resistant osteosarcoma cell lines. Drug efflux and intracellular drug accumulation were measured by flow cytometry. The vanadate-sensitive ATPase activity of PGP1 was measured in the presence of a range of anlotinib concentrations. The protein expression level of ABCB1 was detected by Western blotting and immunofluorescence analysis. Our results showed that anlotinib significantly increased the sensitivity of KHOSR2 and U2OSR2 cells (which overexpress PGP1) to chemotherapeutic agents in vitro and in a KHOSR2 xenograft nude mouse model in vivo. Mechanistically, anlotinib increases the intracellular accumulation of PGP1 substrates by inhibiting the efflux function of PGP1 in multidrug-resistant cell lines. Furthermore, anlotinib stimulated the ATPase activity of PGP1 but affected neither the protein expression level nor the localization of PGP1. In animal studies, anlotinib in combination with doxorubicin (DOX) significantly decreased the tumor growth rate and the tumor size in the KHOSR2 xenograft nude mouse model. Overall, our findings suggest that anlotinib may be useful for circumventing MDR to other conventional antineoplastic drugs.

The regulatory roles of long noncoding RNAs in osteoporosis.

Osteoporosis is a common metabolic bone disease characterized by low bone mineral density (BMD) and microarchitectural deterioration of bone tissue, which leads to decreased bone strength and increased fracture risk. Osteoporosis mainly results from a disruption of the balance between bone formation mediated by osteoblasts and bone resorption mediated by osteoclasts. At present, the molecular mechanisms underlying osteoporosis are still not fully understood. Long noncoding RNAs (lncRNAs) are RNA molecules that exceed 200 nucleotides (nt) in length and have limited or no protein-coding capacity. Over the past decade, numerous lncRNAs have been demonstrated to participate in multiple biological processes and to play essential roles in the pathogenesis of various diseases. In this review, we summarize recent progress in research on lncRNAs in osteoporosis and mainly focus on their regulatory roles in osteogenesis and osteoclastogenesis. Moreover, we briefly discuss the potential clinical applications of lncRNAs in osteoporosis.

3D Printing of Highly Sensitive and Large-Measurement-Range Flexible Pressure Sensors with a Positive Piezoresistive Effect.

Piezoresistive composite-based flexible pressure sensors often suffer from a trade-off between the sensitivity and measurement range. Moreover, the sensitivity or measurement range is theoretically limited owing to the negative piezoresistive coefficient, resulting in resistance variation below 100%. Here, flexible pressure sensors were fabricated using the three-dimensional (3D) printing technique to improve both the sensitivity and sensing range through the positive piezoresistive effect. With the addition of carbon nanotubes (CNTs) and fumed silica nanoparticles (SiNPs) as a conductive filler and rheology modifier, respectively, the viscoelastic silicone rubber solution converted to a printable gel ink. Soft and porous composites (SPCs) were then directly printed in air at room temperature. The sensitivity and sensing range of the SPC-based pressure sensor can be simultaneously tuned by adjusting the conducting CNT and insulating SiNP contents. By optimizing the density of the CNT conductive network in the matrix, positive piezoresistive sensitivity (+0.096 kPa-1) and a large linear sensing range (0-175 kPa) were obtained. To demonstrate potential applications, the completely soft SPC-based sensor was successfully used in grasp sensing and gait monitoring systems. The 3D printed sensors were also assembled as a smart artificial sensory array to map the pressure distribution.