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Abstract The exploration of traumatic spinal fractures (TSFs) within the senior demographic has not been thoroughly scrutinized, particularly with respect to variations across genders, age groups, seasonal periods, and causative factors. This retrospective analysis aimed to dissect differences in the prevalence and characteristics of TSFs among the elderly, factoring in gender, age, seasonal timing, and causation. A retrospective analysis was conducted on the medical and imaging records of 1,415 patients, all aged 60 years or older, who were diagnosed with TSFs from 2013 to 2019. This study categorized the data by gender, age groups (60–70, 70–80, and 80 years or older), seasons, and the cause of injuries, including road traffic crashes (RTCs), falls from low heights (LHF), falls from high heights (HHF), and injuries incurred during everyday activities and agricultural labor (DFI). Male patients exhibited notably higher incidences of RTCs, high-height falls (HHFs), outdoor incidents, comas post-injury, fractures of the lower limbs (LLFs), pelvic fractures (PFs), rib fractures (RFs), intra-thoracic injuries (ITIs), intra-abdominal injuries (IAIs), cervical fractures, and spinal cord injuries (SCIs). With advancing age, there was a marked decline in occurrences of RTCs, HHFs, outdoor incidents, RFs, craniocerebral injuries (CCIs), ITIs, cervical fractures, and SCIs, while the incidences of DFIs, indoor incidents, and thoracic and lumbar (T + L) fractures notably increased. During autumn, LLF occurrences were significantly reduced, whereas the winter season saw an increase in thoracic fractures. Spring time was associated with a higher frequency of lumbar fractures and noncontiguous spinal fractures (NSFs). Significant distinctions were observed in the age distribution, injury circumstances, associated injuries, and SCIs between high-energy impacts (RTCs and HHFs) and low-energy traumas (LHFs and DFIs). In the elderly demographic, TSFs exhibited discernible distinctions based on gender, age, seasonal variations, and etiological factors, impacting the nature and circumstances of injuries, associated traumas, complications, fracture sites, and the occurrence of SCIs.

Abstract Gastric cancer is one of the most common malignant tumors, and chemotherapy is the main treatment for advanced gastric cancer. However, chemotherapy resistance leads to treatment failure and poor prognosis in patients with gastric cancer. Multidrug resistance (MDR) is a major challenge that needs to be overcome in chemotherapy. According to recent research, ferroptosis activation is crucial for tumor therapeutic strategies. In this work, we explored the solution to chemoresistance in gastric cancer by investigating the effects of the Chinese medicine monomer baicalin on ferroptosis. Baicalin with different concentrations was used to treat the parent HGC27 and drug-resistant HGC27/L cells of gastric cancer. Cell viability was measured by CCK8, and synergistic effects of baicalin combined with oxaliplatin were evaluated using Synergy Finder software. The effects of baicalin on organelles and cell morphology were investigated using projective electron microscopy. Iron concentration, MDA production and GSH inhibition rate were measured by colorimetry. ROS accumulation was detected by flow cytometry. The ferroptosis-related genes (IREB2, TfR, GPX4, FTH1), P53, and SLC7A11 were analysed by Western blot, and the expression differences of the above proteins between pretreatment and pretreatment of different concentrations of baicalin, were assayed in both parental HGC27 cells and Oxaliplatin-resistant HGC27/L cells. Mechanically, Baicalin disrupted iron homeostasis and inhibits antioxidant defense, resulting in iron accumulation, lipid peroxide aggregation, and specifically targeted and activated ferroptosis by upregulating the expression of tumor suppressor gene p53, thereby activating the SLC7A11/GPX4/ROS pathway mediated by it. Baicalin activates ferroptosis through multiple pathways and targets, thereby inhibiting the viability of oxaliplatin-resistant gastric cancer HGC27/L cells and enhancing the sensitivity to oxaliplatin chemotherapy.

Abstract Despite that surgical resection is widely regarded as the most effective approach to the treatment of liver cancer, its safety and efficacy upon centrally located hepatocellular carcinoma (HCC) remain unsatisfactory. In consequence, seeking an integrated treatment, like combined with adjuvant radiotherapy, to enhance the prognosis of patients is of critical importance. By recruiting patients undergoing surgical resection for centrally located HCC ranging from June 2015 to 2020, they were divided into liver resection combined with adjuvant radiotherapy (LR + RT) and mere liver resection (LR) groups. The calculation of propensity score and model of Cox proportional hazards regression were utilized. 193 patients were recruited in aggregation, containing 88 ones undergoing LR + RT, while 105 handled with LR. RT was verified to be an independent factor of prognosis for relapse (HR 0.60). In propensity-score analyses, significant association existed between adjuvant radiotherapy and better disease-free survival (DFS) (Matched, HR 0.60; Adjustment of propensity score, HR 0.60; Inverse probability weighting, HR 0.63). The difference of DFS was apparent within two groups (p value = 0.022), and RT significantly down-regulated early relapse (p value

Platelet-derived growth factor receptor β (PDGFRβ) plays a crucial role in murine haematopoiesis. Baicalein (BAI), a naturally occurring flavonoid, can alleviate disease damage through anti-oxidative, anti-apoptotic, and anti-inflammatory mechanisms. However, whether BAI attenuates oxidative damage in murine haematopoietic cells by PDGFRβ remains unexplored. In this study, we utilized a tert-butyl hydroperoxide (TBHP)-induced BaF3 cell injury model and an ionising radiation (IR)-induced mice injury model to investigate the impact of the presence or absence of PDGFRβ on the pharmacological effects of BAI. In addition, the BAI-PDGFRβ interaction was characterized by molecular docking and dynamics simulations. The results show that a specific concentration of BAI led to increased cell viability, reduced reactive oxygen species (ROS) content, upregulated nuclear factor erythroid 2-related factor 2 (NRF2) expression, and its downstream target genes heme oxygenase 1 (HO-1) and NAD(P)H Quinone Dehydrogenase 1 (NQO1), and activated protein kinase B (AKT) pathway in cells expressing PDGFRβ plasmid and experiencing damage. Similarly, BAI elevated lineage−Sca1+cKIT+ (LSK) cell proportion, promoted haematopoietic restoration, enhanced NRF2-mediated antioxidant response in PDGFRβ+/+ mice. However, despite BAI usage, PDGFRβ knockout mice (PDGFRβ−/−) showed lower LSK proportion and less antioxidant capacity than the total body irradiation (TBI) group. Furthermore, we demonstrated an interaction between BAI and PDGFRβ at the molecular level. Collectively, our results indicate that BAI attenuates oxidative stress injury and helps promote haematopoietic cell recovery through regulation of PDGFRβ.

Abstract Isorhamnetin is a natural flavonoid compound, rich in brass, alkaloids, and sterols with a high medicinal value. This study investigated the effects of isorhamnetin on liver injury and oxidative and inflammatory responses in heat-stroke-affected rats in a dry-heat environment. Fifty Sprague Dawley rats were randomly divided into five groups: normal temperature control (NC, saline), dry-heat control (DHC, saline), low-dose isorhamnetin-pretreated (L-AS, 25 mg/Kg), medium-dose isorhamnetin-pretreated (M-AS, 50 mg/Kg), and high-dose isorhamnetin-pretreated (H-AS, 100 mg/Kg) group. Saline was administered to the NC and DHC groups and corresponding concentrations of isorhamnetin were administered to the remaining three groups for 1 week. Blood and liver tissue were analyzed for oxidative stress and inflammation. The liver histopathological injury score, serum liver enzyme (alanine transaminase, aspartate transaminase, and lactate dehydrogenase), liver oxidative stress index (superoxide dismutase [SOD], catalase [CAT], and malondialdehyde), and inflammation index (tumor necrosis factor α [TNF-α], interleukin [IL]-1β, IL-6, and lipopolysaccharides) were significantly higher in the DHC group than in the NC group (P

Abstract To solve the problem that the macroscopic deformation and failure of coal–rock medium under external loads are easy to be observed while the internal stress transfer mode and path are unclear. Based on the discrete element idea, the numerical models for pure coal or rock samples and coal–rock combination samples with different lithologies and combination methods under concentrated force are established by PFC2D software. Then the influence of coal or rock strength and combination methods on the internal stress transfer law and distribution evolution characteristics of coal–rock medium are discussed from the perspectives of macroscopic stress and mesoscopic force chain, respectively. The results showed that under concentrated load, the macroscopic stress transfer paths within pure coal or rock samples and coal–rock combination samples are primarily in the form of ‘point source radiation’. However, when transferring between coal–rock interfaces, there is a certain interface effect. For pure coal or rock samples, differences in lithology does not change the transfer rules and macro distribution patterns of internal stress, but it can cause changes in internal unit transfer stress value and local area transfer direction. For coal–rock combination samples, the greater the difference in lithology between the two sides of the interface, the more likely the interface effect will occur. In addition, the internal stress transfer is also influenced by the relative stratigraphic relationships of coal and rock. When the stress is transferred from a higher-strength rock to a lower-strength coal mass, the interface effect will be more significant. However, regardless of the combination pattern, the locations where significant stress surges occur are always within the higher strength rock mass near the interface. The findings are helpful to understand the mechanical properties and failure mechanism of mining coal and rock mass, and provide a theoretical basis for the study of the mining-induced mechanical behavior of the floor under the action of the coal pillar.

Study Design Retrospective clinical trial. Purpose To establish a morphological classification of the cervical spinal canal using its parameters. Overview of Literature Cervical spine computed tomography (CT) data of 200 healthy volunteers in 2 years were analyzed. The morphology of the spinal cord was also analyzed. Methods The median sagittal diameter and transverse diameter of the spinal canal from C2 to C7 were measured on CT images. The ratio of the median sagittal diameter to the transverse diameter was calculated. Accordingly, the spinal canal shape of each segment was classified into four, and the specific criteria of lunar phase classification were determined through linear discriminant analysis based on the ratio of the median sagittal diameter to the transverse diameter. The inter-rater reliability of the classification was explored using Kappa coefficients. Finally, the morphology of the different segments of the cervical spinal canal in healthy volunteers was revised and compared. Results According to the ratio of the median sagittal diameter and the transverse diameter of the cervical spinal canal, the lunar phase classification of the cervical bony spinal canal was determined as follows: full-moon >0.65, 0.55< convex-moon ≤0.65, 0.46≤ quarter-moon ≤0.55, and residual-moon 0.05). The frequency of the spinal canal of the residual-moon type was the highest, and the full-moon (6.5%) and residual-moon (7.5%) types of C7 were rare. Conclusions The morphological classification of the cervical spinal canal was established to present anatomical variations. The classification showed good inter-rater reliability.

Epigallocatechin gallate (EGCG), an active constituent of tea, is recognized for its anticancer and anti-inflammatory properties. However, the specific mechanism by which EGCG protects osteoblasts from cadmium-induced damage remains incompletely understood. Here, the action of EGCG was investigated by exposing MC3T3-E1 osteoblasts to EGCG and CdCl2 and examining their growth, apoptosis, and differentiation. It was found that EGCG promoted the viability of cadmium-exposed MC3T3-E1 cells, mitigated apoptosis, and promoted both maturation and mineralization. Additionally, CdCl2 has been reported to inhibit both the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and nuclear factor erythroid 2-related factor 2/heme oxygenase-1(Nrf2/HO-1) signaling pathways. EGCG treatment attenuated cadmium-induced apoptosis in osteoblasts and restored their function by upregulating both signaling pathways. The findings provide compelling evidence for EGCG’s role in attenuating cadmium-induced osteoblast apoptosis and dysfunction through activating the PI3K/AKT/mTOR and Nrf2/HO-1 pathways. This suggests the potential of using EGCG for treating cadmium-induced osteoblast dysfunction.

Promoting the social integration of rural migrants is key to improving the mechanism of rural-urban integration and development. This study utilizes the 2017 China Migrants Dynamic Survey and matched urban macro data to systematically explore the impact of homesteads on the social integration of rural migrants. Research has shown that social integration of rural migrants will be inhibited if they own homesteads. Simultaneously, the degree of inhibition varies according to the individual characteristics of rural migrants, the region to which they belong, and other factors. Specifically, when rural migrants aged 18 to 50 own homesteads, their degree of social integration into the cities they move into will be low. At the same time, for rural migrants in the central region, homestead ownership will not affect their degree of social integration. In addition, the mechanism analysis shows that increased housing expenditure inhibits rural migrants' willingness to integrate. Meanwhile, owning contracted land and owning a house in the city also affect the degree of social integration of rural migrants to a certain extent. The findings of this study can broaden research on the effects of land on the free movement of population factors. In the meantime, it provides theoretical references for improving the level of social integration of migrants, enhancing people's well-being, and improving the mechanism of urban-rural integration and development.

Abstract The neutron capture cross section of $$ ^{181} $$ 181 Ta is relevant to s-process of nuclear astrophysics, extraterrestrial samples analysis in planetary geology and new generation nuclear energy system design. The $$^{181}$$ 181 Ta( $$n,\gamma $$ n , γ ) cross section had been measured between 1 eV and 800 keV at the back-streaming white neutron facility (Back-n) of China spallation neutron source(CSNS) using the time-of-flight (TOF) technique and $$\hbox {C}_{6}\,\hbox {D}_{6}$$ C 6 D 6 liquid scintillator detectors. The experimental results are compared with the data of several evaluated libraries and previous experiments in the resolved and unresolved resonance region. Resonance parameters are extracted using the R-Matrix code SAMMY in the 1–700 eV region. The astrophysical Maxwell average cross section(MACS) from kT = 5 to 100 keV is calculated over a sufficiently wide range of neutron energies. For the characteristic thermal energy of an astrophysical site, at kT = 30keV the MACS value of $$^{181}$$ 181 Ta is 834 ± 75 mb, which shows an obvious discrepancy with the Karlsruhe Astrophysical Database of Nucleosynthesis in Stars (KADoNiS) recommended value 766 ± 15 mb. The new measurements strongly constrain the MACS of $$^{181}$$ 181 Ta( $$n,\gamma $$ n , γ ) reaction in the stellar s-process temperatures.

Abstract VEGF inhibitors are one of the most successful antiangiogenic drugs in the treatment of many solid tumors. Nevertheless, pancreatic adenocarcinoma (PAAD) cells can reinstate tumor angiogenesis via activation of VEGF-independent pathways, thereby conferring resistance to VEGF inhibitors. Bioinformatic analysis showed that BICC1 was one of the top genes involved in the specific angiogenesis process of PAAD. The analysis of our own cohort confirmed that BICC1 was overexpressed in human PAAD tissues and was correlated to increased microvessel density and tumor growth, and worse prognosis. In cells and mice with xenograft tumors, BICC1 facilitated angiogenesis in pancreatic cancer in a VEGF-independent manner. Mechanistically, as an RNA binding protein, BICC1 bounds to the 3’UTR of Lipocalin-2 (LCN2) mRNA and post-transcriptionally up-regulated LCN2 expression in PAAD cells. When its level is elevated, LCN2 binds to its receptor 24p3R, which directly phosphorylates JAK2 and activates JAK2/STAT3 signal, leading to increased production of an angiogenic factor CXCL1. Blocking of the BICC1/LCN2 signalling reduced the microvessel density and tumor volume of PAAD cell grafts in mice, and increased the tumor suppressive effect of gemcitabine. In conclusion, BICC1 plays a pivotal role in the process of VEGF-independent angiogenesis in pancreatic cancer, leading to resistance to VEGF inhibitors. BICC1/LCN2 signaling may serve as a promising anti-angiogenic therapeutic target for pancreatic cancer patients.

Background Extended oral anticoagulant (OA) use is recommended in patients with acute pulmonary embolism (PE) who require secondary thromboprophylaxis. Nevertheless, the optimal length of OA use for the maximum long-term benefit in this patient population has been undefined to date.Methods A retrospective study was performed to explore the role of different length of overall OA use (group 1 (≥1 year of OA use and

Background Glioma is one of the most malignant tumors, which leads to high mortality in cancer patients. At present, there is no effective therapy for glioma. Therefore, it is urgent and necessary to find new molecular targets for anti-glioma therapy. Objective The present study aimed to investigate the role of signal transducer and activator of transcription 1 (STAT1) in the development and progression of human glioma and related mechanisms. Methods According to the instructions of Lipofectamine TM 2000 transfection reagent, we transiently transfected the plasmid pcDNA3.1-STAT1 into glioma U251 cells. Then STAT1 expression in glioma U251 and LN382 cells was detected by Western blot. MTT was performed to assay the proliferative activity of U251 cells after STAT1 transduction, flow cytometry was used to detect cell cycle and apoptosis indicators, cell migration indicator was determined by Wound healing, and Western blot was used for detecting the expression level and change trend of p53, p21, bcl-2, Caspase-8, Cyclin A and Cyclin E in transfected cells. Results Overexpressed STAT1 significantly inhibited U251 cell proliferation and promoted U251 cell apoptosis. Meanwhile, high expression of STAT1 can increase the expression of p53, p21, and Caspase-8 while inhibiting the expression of bcl-2, Cyclin A, and Cyclin E. Conclusion Highly expressed STAT1 inhibits the proliferative activity of human glioma U251 cells and can promote tumor cell apoptosis and block cell cycle progression while regulating the expression of various signal transduction molecules. Thus, STAT1 has a critical function in the development and progression of glioma and is a novel target for glioma therapy.

Abstract To investigate the sex, age, role and geographic differences in traumatic spinal fractures (TSFs) caused by motor vehicle collisions (MVCs) in adults (≥ 18 years old). This was a multicentre retrospective observational study. In total, 798 patients with TSFs caused by MVCs admitted to our hospitals from January 2013 to December 2019 were enrolled. The patterns were summarized with respect to different sexes (male and female), age group (18–60 and ≥ 60), role (driver, passenger and pedestrian) and geographic location (Chongqing and Shenyang). Significant differences in distribution related to district (p = 0.018), role (p

Abstract The morbidity of skin tumors (ST) in China is a great concern as the population ages. No epidemiological survey on ST in elderly communities in China has been reported. A questionnaire survey was conducted among the residents over 60 years old in a community in Shanghai, China from May 1, 2011 to November 30, 2011. The prevalence of cutaneous tumors and associated factors were analyzed. Among 2038 valid cases, a total of 78 (3.8%, 95% CI 3.0–4.7) skin cancers (SC) were confirmed. According to the final multivariate regression analysis, age, gender and previous occupation were the significantly influential factors for SC. Actinic keratosis (AK) accounted for the largest proportion (63, 3.1%) in SC. The head and neck was the physiological site with the highest incidence of SC (64, 82.1%), and AK was the most common (55, 87.3%) in head and neck SC. The common concomitant diseases of SC were hypertension (26, 33.3%) and diabetes mellitus (9, 11.5%). Seborrheic keratosis (SK) was the most common benign skin tumor with a prevalence of 100%. Men and women developed SK in significantly different parts of the body (P

Abstract With the continuous enhancement of human activities, the contradiction between regional development and ecological protection is prominent in the ecologically fragile arid areas. It is of great significance for regional sustainable development to understand the ecological supply and demand problems caused by transformation of land using and formulate ecological compensation scheme scientifically. This study takes Xinjiang in China as the research area. It explores the land use transition characteristics and the changes in carbon supply and demand of Xinjiang using methods such as GIS spatial analysis and modified comparative ecological radiation forcing. Finally, the ecological compensation scheme is studied based on the theory of ecological radiation. The research shows that (I) in the study chronology, most of the areas produced only one change in land use. Land use is gradually developing towards the direction of ecological protection. After 2000, grassland recovered well, and 14,298 km2 of other ecological land was transformed into grassland. (II) The change in the carbon sink of the Xinjiang ecosystem first decreased and then increased, and the ecological deficit area started to appear after 2010. The growth of grassland and cropland areas is essential to enhance the carbon sink capacity of arid zones. (III) The amount of ecological compensation in Xinjiang is 31.47 * 108 yuan, and the proportion of the amount received by ecological compensation areas is related to the distance between the supply and demand areas, the amount of carbon sequestration, and the area of the region. This study provides a reference for achieving the healthy development of sustainable land use ecosystems in arid zones.

Abstract ANO5 encodes transmembrane protein 16E (TMEM16E), an intracellular calcium-activated chloride channel in the endoplasmic reticulum. Mutations in ANO5 are associated with gnathodiaphyseal dysplasia (GDD), a skeletal disorder causing the jaw deformity and long bone fractures. However, the coordinated mechanism by which ANO5 mediates bone homeostasis in GDD remains poorly defined. Here, we show that ablation of Ano5 reduced intracellular calcium transients, leading to defects in osteogenesis and osteoclastogenesis and thus bone dysplasia. We found a causative de novo ANO5 frameshift insertion mutation (p.L370_A371insDYWRLNSTCL) in a GDD family with osteopenia, accompanied by a decrease in TMEM16E expression and impaired RANKL-induced intracellular calcium ([Ca2+]i) oscillations in osteoclasts. Moreover, using Ano5 knockout (KO) mice, we found that they exhibited low bone volume, abnormal calcium deposits, and defective osteoblast and osteoclast differentiation. We also showed that Ano5 deletion in mice significantly diminished [Ca2+]i oscillations in both osteoblasts and osteoclasts, which resulted in reduced WNT/β-Catenin and RANKL-NFATc1 signaling, respectively. Osteoanabolic treatment of parathyroid hormone was effective in enhancing bone strength in Ano5 KO mice. Consequently, these data demonstrate that Ano5 positively modulates bone homeostasis via calcium signaling in GDD.

It is common for elderly patients to develop postoperative cognitive dysfunction (POCD), but the pathophysiological mechanisms have not yet been fully explored. NLRP3 inflammasome activation and mitophagy impairment was involved in neurodegenerative disease. This study investigated the interaction of NLRP3 inflammasome and mitophagy in sevoflurane-induced cognitive dysfunction. We found that sevoflurane induced cleaved caspase-1 level, IL-1β and IL-18 maturation, and activated NLRP3 inflammasome in aged mice and the primary hippocampus neuron. The cleaved caspase-1 was demonstrated in microglia of hippocampus. Ac-YVAD-cmk, a selected caspase-1 inhibitor, reduced the expression of cleaved caspase-1, IL-1β, IL-18 and NLRP3 inflammasome activation induced by sevoflurane. Ac-YVAD-cmk ameliorated learning ability impairment in aged mice induced by sevoflurane using Morris water maze. Moreover, Ac-YVAD-cmk reversed the mitophagy flux dysfunction induced by sevoflurane in aged mice by western blotting, immunostaining and mt-Keima reporters. For the first time, we found caspase-1 inhibitor mitigated mitochondria dysfunction and revised mitophagy impairment induced by sevoflurane.

Abstract When studying the human settlement process, it is of great significance to understand the prehistoric environment, economy and society by exploring the human–land relationship and the evolution of civilization reflected by the settlement environment. This paper explores the natural and social environmental preferences of early human settlements in Xinjiang, China, from the Palaeolithic to the Bronze Age (45 ka BP–2250 a BP). Through the characteristics of settlement preferences, the distribution of settlements is accurately predicted, and the relationship between settlement preferences and the evolution of the environment and civilization is verified and discussed. We summarize the needs and conditions of early human settlement from the perspectives of the social environment and natural environment and explain the stages, consistency and differentiation of the spatial and temporal evolution of settlement preferences with the interaction of adaptation and transformation. On this basis, we discuss the logical focuses and content of early human settlement preference research. This research provides a reference for the process, representation, driving mode, and research ideas of early human settlement preferences.

Exogenous melatonin (MT) is widely used in fruit preservation, and can increase the storage time and delay the quality deterioration. Firstly, it was found that 150 μM MT was the optimal concentration to treat ‘Xinli No.7’ under storage at 4 °C for 60 days. MT could significantly improve oxidase activity and inhibit the reduction of physiological indexes, including pulp hardness, weight loss, titratable acid and soluble solid content. MT could also reduce ethylene release and limit the reduction of fruit aroma. The average content of fruit aroma substance increased by 43.53%. A relevant RNA-Seq database was built to further explore the regulation mechanism of MT. A total of 2,761 differentially expressed genes (DEGs) were identified. DEGs were enriched in 64 functional groups and 191 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. DEGs were mainly enriched in alpha-linolenic acid metabolism, fatty acid metabolism and plant hormone signal transduction pathway. The gene pycom09g05270 belonging to long chain acyl-CoA synthetase family and participating in fatty acid metabolism pathway was identified, and its expression level was consistent with fragments per kilobase per million mapped reads (FPKM) values, implying that pycom09g05270 might play a vital role in maintaining quality during the storage process.

Abstract Wnt/β-catenin signaling is activated in the heart after myocardial infarction (MI). This study aims to investigate if β-catenin deletion affects post-MI ion channel gene alterations and ventricular tachycardias (VT). MI was induced by permanent ligation of left anterior descending artery in wild-type (WT) and cardiomyocyte-specific β-catenin knockout (KO) mice. KO mice showed reduced susceptibility to VT (18% vs. 77% in WT) at 8 weeks after MI, associated with reduced scar size and attenuated chamber dilation. qPCR analyses of both myocardial tissues and purified cardiomyocytes demonstrated upregulation of Wnt pathway genes in border and infarct regions after MI, including Wnt ligands (such as Wnt4) and receptors (such as Fzd1 and Fzd2). At 1 week after MI, cardiac sodium channel gene (Scn5a) transcript was reduced in WT but not in KO hearts, consistent with previous studies showing Scn5a inhibition by Wnt/β-catenin signaling. At 8 weeks after MI when Wnt genes have declined, Scn5a returned to near sham levels and K+ channel gene downregulations were not different between WT and KO mice. This study demonstrated that VT susceptibility in the chronic phase after MI is reduced in mice with cardiomyocyte-specific β-catenin deletion primarily through attenuated structural remodeling, but not ion channel gene alterations.

With the ageing of the global population, the incidence of osteoporotic vertebral compression fractures (OVCFs) is increasing. To assess the safety and efficacy of O-arm- and guide-device-assisted personalized percutaneous kyphoplasty (PKP) for treating thoracolumbar OVCFs, a total of 38 consecutive thoracolumbar OVCF patients who underwent bilateral PKP assisted with an O-arm and a guide device (O-GD group, n = 16) or traditional fluoroscopy (TF group, n = 22) from January 2020 to December 2021 were retrospectively reviewed, and their epidemiologic, clinical and radiological outcomes were analysed. The operation time was significantly decreased (p < 0.001) in the O-GD group (38.3 ± 12.2 min) compared with the TF group (57.2 ± 9.7 min). The number of intraoperative fluoroscopy exposures was significantly decreased (p < 0.001) in the O-GD group (31.9 ± 4.5) compared with the TF group (46.7 ± 7.2). Intraoperative blood loss was significantly decreased (p = 0.031) in the O-GD group (6.9 ± 2.5 mL) compared with the TF group (9.1 ± 3.3 mL). No significant difference (p = 0.854) in the volume of injected cement was observed between the O-GD group (6.8 ± 1.3 mL) and the TF group (6.7 ± 1.7 mL). Both the clinical and radiological outcomes, including the visual analogue scale score for pain, Oswestry Disability Index and anterior height and local kyphotic angle of the fractured vertebrae, were significantly improved at the postoperative and final follow-up but did not differ between the two groups. The incidence of cement leakage and refracture of the vertebral body was similar in the two groups (p = 0.272; p = 0.871). Our preliminary study demonstrated that O-GD-assisted PKP is a safe and effective procedure that presents a significantly shorter operation time, fewer intraoperative fluoroscopy exposures and less intraoperative blood loss than the TF technique.

Rural settlements in oasis are primary habitations, and their changes are related to natural environment and anthropogenic activities. The spatiotemporal variations of rural settlements in an oasis are significant in arid regions. In this study, Qipan Township (QPT) and Yamansu Township (YMST) were chosen as a case study and validation case, respectively. Datasets, including Landsat images in 2002, 2010, and 2018, were collected. The cellular automata (CA)-agent-based model (ABM) and patch-generating land use simulation (PLUS) model were used to simulate the spatiotemporal dynamic variations of rural settlement and other land use types in the oasis in this study. Natural environmental, socioeconomic conditions, and human decision-making are the three driving factors that were used in the model. Human decision-making involves the actions of two types of agents: authority agent and resident agent. On the basis of land use data of 2002 and 2010, the rural settlement and other land use in 2018 were predicted using the CA-MAS and PLUS models. The following results were obtained: First, human decision-making behaviors were the leading factor in the changes of rural settlements in the CA-ABM model. Second, CA based on multiple random seed (CARS) of PLUS could better simulate the spatiotemporal variations of QPT rural settlements than CA-ABM and linear regression of PLUS. Similarly, CARS of PLUS also simulated the spatiotemporal evolution of rural settlements in YMST with high accuracy. Third, the areas of croplands, roads, and residential lands in QPT will expand to 20.7, 5.7, and 4.6 km2, respectively, in 2026, but the unused land will shrink, as predicted by CARS of PLUS. This study provides a scientific basis for the environmental protection of rural settlements in the oasis and sustainable settlement planning in arid regions.

Abstract Background The present study aimed to verify whether long noncoding RNA (lncRNA) MALAT1 is involved in brain tissue damage induced by ischemia-reperfusion injury, and to explore the mechanism by which MALAT1 regulates aquaporin 4 (AQP4). Methods In this study, we established glucose deprivation (OGD)/reoxygenation (RX) astrocyte cell model and middle cerebral artery occlusion (MCAO)/reperfusion mouse model in vitro and in vivo. Then cell counting kit-8 assay, flow cytometry analysis, Triphenyltetrazolium chloride (TTC) staining, and western blotting were used to determine cell viability, cell apoptosis, cerebral infarction volume, and the abundance of AQP4, respectively. Results We found that the level of MALAT1 was significantly upregulated in both the MCAO/reperfusion model and OGD/RX model. Knockdown of MALAT1 increased cell viability and reduced cell apoptosis in MA-C cells, while an AQP4 siRNA combined with a siRNA targeting MALAT1 could not enhance this effect. Further experiments showed that MALAT1 positively regulated AQP4 expression via miR-145. The MALAT1 siRNA did not alleviate the exacerbation of damage after miR-145 inhibitor action. However, an miR-145 inhibitor reversed the protection effects of MALAT1, indicating that MALAT1 silencing protects against cerebral ischemia-reperfusion injury through miR-145. TTC staining showed that the infracted area of whole brain was significantly attenuated in treated with sh-MALAT1 group in vivo. Conclusion Taken together, our study confirmed that MALAT1 promotes cerebral ischemia-reperfusion injury by affecting AQP4 expression through competitively binding miR-145, indicating that MALAT1 might be a new therapeutic target for treatment cerebral ischemic stroke.

Abstract Background Rats with hyperandrogen-induced polycystic ovary syndrome (PCOS) have been shown to develop ovarian oxidative stress (OS) and fibrosis. The Sirt1 agonist, resveratrol, can reduce OS through inhibiting p66Shc in other models of OS. Methods We created a rat PCOS model with increased OS levels following treatment with one of the two androgens, dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT). The PCOS related features were determined by measurement of malondialdehyde (MDA) and superoxide dismutase (SOD) levels or by examining the reactive oxygen species (ROS) levels using the DCF-DA probe. The potential mechanisms by which p66Shc/Sirt1 mediates ovarian fibrosis were explored by western blotting, quantitative reverse transcription-PCR, immunofluorescence staining, and immunohistochemistry. Results Hyperandrogen dramatically augmented OS and activation of fibrotic factors in the ovary. Our data demonstrated that treatment with resveratrol enhanced Sirt1 and decreased ovarian OS as well as inhibited phosphorylation of p66Shc both in vivo and in vitro. The treatment suppressed fibrotic factor activation and improved ovarian morphology. Lentivirus- or siRNA-mediated p66Shc knockdown resulted in a dramatic enhancement of Sirt1 expression, down-regulation of ROS and suppression of fibrotic factors in granulosa cells. Moreover, p66Shc overexpression markedly increased the expression of fibrotic factors. Additionally, silencing Sirt1 induced a dramatic increase in p66Shc and enhanced activation of fibrotic factors. Conclusions p66Shc may be a direct target of Sirt1 for inducing ROS and thus promoting fibrosis. Further exploration of the mechanisms of p66Shc in both fibrosis and OS may provide novel therapeutic strategies that will facilitate the improvement in PCOS symptoms and reproductive functions.

Abstract Background Aging is believed to have a close association with cardiovascular diseases, resulting in various pathological alterations in blood vessels, including vascular cell phenotypic shifts. In aging vessels, the microRNA(miRNA)-mediated mechanism regulating the vascular smooth muscle cell (VSMC) phenotype remains unclarified. MiRNA microarray was used to compare the expressions of miRNAs in VSMCs from old rats (oVSMCs) and young rats (yVSMCs). Quantitative reverse transcription real-time PCR (qRT-PCR) and small RNA transfection were used to explore the miR-542-3p expression in oVSMCs and yVSMCs in vitro. Calcification induction of yVSMCs was conducted by the treatment of β-glycerophosphate (β-GP). Alizarin red staining was used to detect calcium deposition. Western blot and qRT-PCR were used to investigate the expression of the smooth muscle markers, smooth muscle 22α (SM22α) and calponin, and the osteogenic markers, osteopontin (OPN), and runt-related transcription factor 2 (Runx2). Lentivirus was used to overexpress miR-542-3p and bone morphogenetic protein 7 (BMP7) in yVMSCs. Luciferase reporter assay was conducted to identify the target of miR-542-3p. Results Compared with yVSMCs, 28 downregulated and 34 upregulated miRNAs were identified in oVSMCs. It was confirmed by qRT-PCR that oVSMC expressed four times lower miR-542-3p than yVSMCs. Overexpressing miR-542-3p in yVSMCs suppressed the osteogenic differentiation induced by β-GP. Moreover, miR-542-3p targets BMP7 and overexpressing BMP7 in miR-542-3p–expressing yVSMCs reverses miR-542-3p’s inhibition of osteogenic differentiation. Conclusions miR-542-3p regulates osteogenic differentiation of VSMCs through targeting BMP7, suggesting that the downregulation of miR-542-3p in oVSMCs plays a crucial role in osteogenic transition in the aging rat.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women. Moderate aerobic exercise intervention is considered an initial treatment strategy for managing PCOS. Brain-derived neurotrophic factor (BDNF) is an important molecular mediator and a beneficial response to exercise. We aimed to investigate the expression pattern and underlying molecular mechanisms of this neurotrophic factor during follicle development in ovarian tissues. The PCOS model was established by subcutaneous injection of 60 mg/kg dehydroepiandrosterone (DHEA) into the neck of Sprague Dawley rats for 35 consecutive days. PCOS rats then received aerobic exercise for 8 weeks. Body/ovarian weight and peripheral serum hormone levels were observed. Immunohistochemistry combined with Western blot analysis and fluorescence quantitative polymerase chain reaction were used to detect the changes in BDNF-TrkB/p75NTR pathway, apoptosis, and inflammatory factors. We show that moderate aerobic exercise not only reverses the PCOS phenotype but also activates the BDNF-TrkB pathway and initiates downstream targets. p-TrkB upregulates and phosphorylates phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) to inhibit apoptosis. In addition, aerobic exercise therapy reduces the high expression of p75NTR in the ovarian tissue of PCOS rats and initiates the anti-apoptotic effect from the downstream pathway of NF-κB/JNK. Our in vitro results state that treatment with BDNF ameliorated dihydrotestosterone (DHT)-induced granulosa cells (GCs) apoptosis by provoking p-TrkB activation and upregulating the PI3K/AKT pathway. The present study suggests that moderate aerobic exercise regulates follicular dysfunction in PCOS-like rats. One possible mechanism is to initiate the BDNF-mediated anti-apoptotic signaling pathway.

Background: S1PR1-STAT3 inter-regulatory loop was initially suggested to be oncogenic in several cancer cells. However, the clinical relevance of this mechanism in tumor progression, disease prognosis and drug response was not established. Methods: The correlations between S1PR1 transcription, overall survival and chemotherapy response of GC patients were tested using a large clinical database. The relevance of S1PR1 expression and STAT3 activation in both tumor tissues and cancer cell lines was also tested. The effect of S1PR1 high expression achieved by persistent STAT3 activation on tumor cell drug resistance was investigated in vitro and in vivo. Findings: An enhanced S1PR1 expression was highly related with a reduced overall survival time and a worse response to chemotherapy drug and closer correlation to STAT3 in gastric cancer patients. The issue chip analysis showed that the expressions of S1PR1 and STAT3 activation were increased in higher graded gastric cancer (GC) tissues. Cellular studies supported the notion that the high S1PR1 expression was responsible for drug resistance in GC cells through a molecular pattern derived by constitutive activation of STAT3. The disruption of S1PR1-STAT3 signaling significantly re-sensitized drug resistance in GC cells in vitro and in vivo. Interpretation: S1PR1-STAT3 signaling may participate drug resistance in GC, thus could serve as a drug target to increase the efficacy of GC treatment. Fund: This work was supported by the National Natural Science Foundation of China (No. 81570775, 81471095), the grant from the research projects in traditional Chinese medicine industry of China (No. 201507004-2).

The study aims to depict the temporal and spatial distributions of hand-foot-and-mouth disease (HFMD) in Xinjiang, China and reveal the relationships between the incidence of HFMD and meteorological factors in Xinjiang. With the national surveillance data of HFMD in Xinjiang and meteorological parameters in the study area from 2008 to 2016, in GeoDetector Model, we examined the effects of meteorological factors on the incidence of HFMD in Xinjiang, China, tested the spatial-temporal heterogeneity of HFMD risk, and explored the temporal-spatial patterns of HFMD through the spatial autocorrelation analysis. From 2008 to 2016, the HFMD distribution showed a distinct seasonal pattern and HFMD cases typically occurred from May to July and peaked in June in Xinjiang. Relative humidity, precipitation, barometric pressure and temperature had the more significant influences on the incidence of HFMD than other meteorological factors with the explanatory power of 0.30, 0.29, 0.29 and 0.21 (P

[This corrects the article DOI: 10.1371/journal.pone.0188029.].

Climate change has a global impact on the water cycle and its spatial patterns, and these impacts are more pronounced in eco-fragile regions. Arid regions are significantly affected by human activities like farming, and climate change, which influences lake water volumes, especially in different latitudes. This study integrates radar altimetry data from 2002 to 2018 with optical remote sensing images to analyze changes in the lake areas, levels, and volumes at different altitudes in Xinjiang, China. We analyzed changes in lake volumes in March, June, and October and studied their causes. The results showed large changes in the surface areas, levels, and volumes of lakes at different altitudes. During 2002–2010, the lakes in low- and medium-altitude areas were shrinking but lakes in high altitude areas were expanding. Monthly analysis revealed more diversified results: the lake water levels and volumes tended to decrease in March (−0.10 m/year, 37.55×108 m3) and increase in June (0.03 m/year, 3.48×108 m3) and October (0.04 m/year, 26.90×108 m3). The time series lake water volume data was reconstructed for 2011 to 2018 based on the empirical model and the total lake water volume showed a slightly increasing trend during this period (71.35×108 m3). We hypothesized that changes in lake water at high altitudes were influenced by temperature-induced glacial snow melt and lake water in low- to medium-altitude areas was most influenced by human activities like agricultural irrigation practices.

Estimating water requirements and water balance for irrigated agricultural areas are important and will facilitate the efficient allocation of water resources for agriculture while minimizing the impact on natural ecosystems in arid regions. Based on the Penman-Monteith formula and GIS technology, the irrigation water requirements (IWR) of three main crops (cotton, corn and wheat) during the growing season were estimated and their spatio-temporal changes over the past 23 years (1995–2017) were analyzed in Xinjiang province, China. Our results indicated a dramatic increase in IWR from 14.12 billion m3 in 1995 to 38.99 billion m3 in 2017 due to the rapid cropland expansion of approximately 2.58 × 104 km2 in this period. Monthly IWR usually peaked in summer from May to July and varied in different basins. From the perspective of crops, cotton was identified to have consumed the largest amount of water, reaching 26.39 billion m3 in 2017, accounting for 67.68% of total water consumption. Spatially, the fastest increasing rate of IWR was Tarim Basin, which was attributable to the increase in water requirement of cotton. By comparing IWR and actual irrigation of Xinjiang in 2014, the amount of water scarcity had reached −15.01 billion m3 (−9.80 billion m3 in Tarim Basin and −6.58 billion m3 in Junggar Basin). The planting areas of three main crops (wheat, corn and cotton) were more sensitive to IWR than rising temperature indicated by our model. This study is of great significance for the scientific allocation of water resources in the irrigated areas of the different prefectures of Xinjiang.

Abstract The resolution of electron-potential maps in single-particle cryo-electron microscopy (cryoEM) is approaching atomic or near- atomic resolution. However, no program currently exists for de novo cryoEM model building at resolutions exceeding beyond 3.5 Å. Here, we present a program, EMBuilder, based on template matching, to generate cryoEM models at high resolution. The program identifies features in both secondary-structure and Cα stages. In the secondary structure stage, helices and strands are identified with pre-computed templates, and the voxel size of the entire map is then refined to account for microscopic magnification errors. The identified secondary structures are then extended from both ends in the Cα stage via a log-likelihood (LLK) target function, and if possible, the side chains are also assigned. This program can build models of large proteins (~1 MDa) in a reasonable amount of time (~1 day) and thus has the potential to greatly decrease the manual workload required for model building of high-resolution cryoEM maps.

Background Worldwide cultivation of maize is often impacted negatively by drought stress. Hyperosmolality-gated calcium-permeable channels (OSCA) have been characterized as osmosensors in Arabidopsis. However, the involvement of members of the maize OSCA (ZmOSCA) gene family in response to drought stress is unknown. It is furthermore unclear which ZmOSCA gene plays a major role in genetic improvement of drought tolerance in Maize. Methods We predicted the protein domain structure and transmembrane regions by using the NCBI Conserved Domain Database database and TMHMM server separately. The phylogeny tree was built by Mega7. We used the mixed linear model in TASSEL to perform the family-based association analysis. Results In this report, 12 ZmOSCA genes were uncovered in the maize genome by a genome-wide survey and analyzed systematically to reveal their synteny and phylogenetic relationship with the genomes of rice, maize, and sorghum. These analyses indicated a relatively conserved evolutionary history of the ZmOSCA gene family. Protein domain and transmembrane analysis indicated that most of the 12 ZmOSCAs shared similar structures with their homologs. The result of differential expression analysis under drought at various stages, as well as the expression profiles in 15 tissues, revealed a functional divergence of ZmOSCA genes. Notably, the expression level of ZmOSCA4.1 being up-regulated in both seedlings and adult leaves. Notably, the association analysis between genetic variations in these genes and drought tolerance was detected. Significant associations between genetic variation in ZmOSCA4.1 and drought tolerance were found at the seedling stage. Our report provides a detailed analysis of the ZmOSCAs in the maize genome. These findings will contribute to future studies on the functional characterization of ZmOSCA proteins in response to water deficit stress, as well as understanding the mechanism of genetic variation in drought tolerance in maize.

The ovary is the main regulator of female fertility. Granulosa cell dysfunction may be involved in various reproductive endocrine disorders. Here we investigated the effect of insulin resistance on the metabolism and function of ovarian granulosa cells, and dissected the functional status of the mitogen-activated protein kinase signaling pathway in these cells. Our data showed that dexamethasone-induced insulin resistance in mouse granulosa cells reduced insulin sensitivity, accompanied with an increase in phosphorylation of p44/42 mitogen-activated protein kinase. Furthermore, up-regulation of cytochrome P450 subfamily 17 and testosterone and down-regulation of progesterone were observed in insulin-resistant mouse granulosa cells. Inhibition of p44/42 mitogen-activated protein kinase after induction of insulin resistance in mouse granulosa cells decreased phosphorylation of p44/42 mitogen-activated protein kinase, downregulated cytochrome P450 subfamily 17 and lowered progesterone production. This insulin resistance cell model can successfully demonstrate certain mechanisms such as hyperandrogenism, which may inspire a new strategy for treating reproductive endocrine disorders by regulating cell signaling pathways.

SOX2OT has been demonstrated to be aberrantly expressed in several types of cancer and maybe serve as a prognostic marker for cancer patients. However, most individual studies have been limited by small sample sizes and controversial results. Therefore, the present meta-analysis was conducted to analyze available data to reveal the potential clinical application of SOX2OT on cancer prognosis, tumor progression, distance metastasis and lymph node metastasis. Up to February 20, 2017, literature collections were conducted by comprehensive searching electronic databases, including Cochrane Library, PubMed, Embase, BioMed Central, Springer, ScienceDirect, ISI Web of Knowledge, together with three Chinese databases: China National Knowledge Internet (CNKI), Weipu and Wanfang. The hazard ratios (HR) with 95% confidence interval (95% CI) were calculated to assess the strength of the association. Five studies with a total of 481 cancer patients were included in the present meta-analysis. The results indicated that elevated SOX2OT significantly predicted unfavorable overall survival (OS) (HR = 2.44, 95% CI: 1.75-3.39, P

BACKGROUND:Graves' disease is the most common form of autoimmune thyroid disorder, characterized by hyperthyroidism due to circulating autoantibodies. To address the pathological features and establish a therapeutic approach of this disease, an animal model carrying the phenotype of Graves' disease (GD) in concert with Graves' Ophthalmopathy (GO) will be very important. However, there are no ideal animal models that are currently available. The aim of the present study is to establish an animal model of GD and GO disease, and its pathological features were further characterized. METHODS:A recombinant plasmid pcDNA3.1- T289 was constructed by inserting the TSHR A-subunit gene into the expression vector pcDNA3.1, and genetic immunization was successfully performed by intramuscular injection of the plasmid pcDNA3.1-T289 on female 8-week-old BALB/c mice. Each injection was immediately followed by in vivo electroporation using ECM830 square wave electroporator. Morphological changes of the eyes were examined using 7.0T MRI scanner. Levels of serum T4 and TSHR antibodies (TRAb) were assessed by ELISA. The pathological changes of the thyroid and orbital tissues were examined by histological staining such as H&E staining and Alcian blue staining. RESULTS:More than 90% of the immunized mice spontaneously developed goiter, and about 80% of the immunized mice manifested increased serum T4 and TRAb levels, combined with hypertrophy and hyperplasia of thyroid follicles. A significantly increased synthesis of hyaluronic acid was detected in in the immunized mice compared with the control groups. CONCLUSION:We have successfully established an animal model manifesting Graves' hyperthyroidism and ophthalmopathy, which provides a useful tool for future study of the pathological features and the development of novel therapies of the diseases.

BACKGROUND:"Evolution Canyon" (ECI) at Lower Nahal Oren, Mount Carmel, Israel, is an optimal natural microscale model for unraveling evolution in action highlighting the basic evolutionary processes of adaptation and speciation. A major model organism in ECI is wild emmer, Triticum dicoccoides, the progenitor of cultivated wheat, which displays dramatic interslope adaptive and speciational divergence on the tropical-xeric "African" slope (AS) and the temperate-mesic "European" slope (ES), separated on average by 250 m. METHODS:We examined 278 single sequence repeats (SSRs) and the phenotype diversity of the resistance to powdery mildew between the opposite slopes. Furthermore, 18 phenotypes on the AS and 20 phenotypes on the ES, were inoculated by both Bgt E09 and a mixture of powdery mildew races. RESULTS:In the experiment of genetic diversity, very little polymorphism was identified intra-slope in the accessions from both the AS or ES. By contrast, 148 pairs of SSR primers (53.23%) amplified polymorphic products between the phenotypes of AS and ES. There are some differences between the two wild emmer wheat genomes and the inter-slope SSR polymorphic products between genome A and B. Interestingly, all wild emmer types growing on the south-facing slope (SFS=AS) were susceptible to a composite of Blumeria graminis, while the ones growing on the north-facing slope (NFS=ES) were highly resistant to Blumeria graminis at both seedling and adult stages. CONCLUSION/SIGNIFICANCE:Remarkable inter-slope evolutionary divergent processes occur in wild emmer wheat, T. dicoccoides at EC I, despite the shot average distance of 250 meters. The AS, a dry and hot slope, did not develop resistance to powdery mildew, whereas the ES, a cool and humid slope, did develop resistance since the disease stress was strong there. This is a remarkable demonstration in host-pathogen interaction on how resistance develops when stress causes an adaptive result at a micro-scale distance.

Somatic mutations in the CALR gene have been recently identified as acquired alterations in myeloproliferative neoplasms (MPNs). In this study, we evaluated mutation frequencies, laboratory features, and granulocyte activation in Chinese patients with MPNs. A combination of qualitative allele-specific polymerase chain reaction and Sanger sequencing was used to detect three driver mutations (i.e., CALR, JAK2V617F, and MPL). CALR mutations were identified in 8.4% of cases with essential thrombocythemia (ET) and 5.3% of cases with primary myelofibrosis (PMF). Moreover, 25% of polycythemia vera, 29.5% of ET, and 48.1% of PMF were negative for all three mutations (JAK2V617F, MPL, and CALR). Compared with those patients with JAK2V617F mutation, CALR-mutated ET patients displayed unique hematological phenotypes, including higher platelet counts, and lower leukocyte counts and hemoglobin levels. Significant differences were not found between Chinese PMF patients with mutants CALR and JAK2V617F in terms of laboratory features. Interestingly, patients with CALR mutations showed markedly decreased levels of leukocyte alkaline phosphatase (LAP) expression, whereas those with JAK2V617F mutation presented with elevated levels. Overall, a lower mutant rate of CALR gene and a higher triple-negative rate were identified in the cohort of Chinese patients with MPNs. This result indicates that an undiscovered mutant gene may have a significant role in these patients. Moreover, these pathological features further imply that the disease biology varies considerably between mutants CALR and JAK2V617F.

Sexual size dimorphism (SSD) is widespread within the animal kingdom. Rensch's rule describes a relationship between SSD and body size: SSD increases with body size when males are the larger sex, and decreases with body size when females are the larger sex. Rensch's rule is well supported for taxa that exhibit male-biased SSD but patterns of allometry among taxa with female-biased size dimorphism are mixed, there is evidence both for and against the rule. Furthermore, most studies have investigated Rensch's rule across a variety of taxa; but among-population studies supporting Rensch's rule are lacking, especially in taxa that display only slight SSD. Here, we tested whether patterns of intraspecific variation in SSD in greater horseshoe bats conform to Rensch's rule, and evaluated the contribution of latitude to Rensch's rule. Our results showed SSD was consistently female-biased in greater horseshoe bats, although female body size was only slightly larger than male body size. The slope of major axis regression of log10 (male) on log10 (female) was significantly different from 1. Forearm length for both sexes of greater horseshoe bats was significantly negatively correlated with latitude, and males displayed a slightly but nonsignificant steeper latitudinal cline in body size than females. We suggest that variation in patterns of SSD among greater horseshoe bat populations is consistent with Rensch's rule indicating that males were the more variable sex. Males did not have a steeper body size-latitude relationship than females suggesting that sex-specific latitudinal variation in body size may not be an important contributing factor to Rensch's rule. Future research on greater horseshoe bats might best focus on more comprehensive mechanisms driving the pattern of female-biased SSD variation.

Acute myeloid leukemia patients with complex karyotype (CK-AML) account for approximately 10-15% of adult AML cases, and are often associated with a poor prognosis. Except for about 70% of CK-AML patients with biallelic inactivation of TP53, the leukemogenic mechanism in the nearly 30% of CK-AML patients with wild-type TP53 has remained elusive. In this study, 15 cases with complex karyotype and wild-type TP53 were screened out of 140 de novo AML patients and the expression levels of MDM4, a main negative regulator of p53-signaling pathway, were detected. We ruled out mutations in genes associated with a poor prognosis of CK-AML, including RUNX1 or FLT3-ITD. The mRNA expression levels of the full-length of MDM4 (MDM4FL) and short isoform MDM4 (MDM4S) were elevated in CK-AML relative to normal karyotype AML (NK-AML) patients. We also explored the impact of MDM4 overexpression on the cell cycle, cell proliferation and the spindle checkpoint of HepG2 cells, which is a human cancer cell line with normal MDM4 and TP53 expression. The mitotic index and the expression of p21, BubR1 and Securin were all reduced following Nocodazole treatment. Moreover, karyotype analysis showed that MDM4 overexpression might lead to aneuploidy or polyploidy. These results suggest that MDM4 overexpression is related to CK-AML with wild-type TP53 and might play a pathogenic role by inhibiting p53-signal pathway.

OBJECTIVE: To compare the von Mises stresses of the internal fixation devices among different short segment pedicle screw fixation techniques to treat thoracic 12 vertebral fractures, especially the mono-segment pedicle screw fixation and intermediate unilateral pedicle screw fixation techniques. METHODS: Finite element methods were utilised to investigate the biomechanical comparison of the four posterior short segment pedicle screw fixation techniques (S4+2: traditional short-segment 4 pedicle screw fixation [SPSF]; M4+2: mono-segment pedicle screw fixation; I6+2: intermediate bilateral pedicle screw fixation; and I5+2: intermediate unilateral pedicle screw fixation). RESULTS: The range of motion (ROM) in flexion, axial rotation, and lateral bending was the smallest in the I6+2 fixation model, followed by the I5+2 and S4+2 fixation models, but lateral bending was the largest in the M4+2 fixation model. The maximal stress of the upper pedicle screw is larger than the lower pedicle screw in S4+2 and M4+2. The largest maximal von Mises stress was observed in the upper pedicle screw in the S4+2 and M4+2 fixation models and in the lower pedicle screw in the I6+2 and I5+2 fixation models. The values of the largest maximal von Mises stress of the pedicle screws and rods during all states of motion were 263.1 MPa and 304.5 MPa in the S4+2 fixation model, 291.6 MPa and 340.5 MPa in the M4+2 fixation model, 182.9 MPa and 263.2 MPa in the I6+2 fixation model, and 269.3 MPa and 383.7 MPa in the I5+2 fixation model, respectively. Comparing the stress between different spinal loadings, the maximal von Mises stress of the implants were observed in flexion in all implanted models. CONCLUSION: Additional bilateral pedicle screws at the level of the fracture to SPSF may result in a stiffer construct and less von Mises stress for pedicle screws and rods. The largest maximal von Mises stress of the pedicle screws during all states of motion were observed in the mono-segment pedicle screw fixation technique.

The altered composition of immune cells in peripheral blood has been reported to be associated with cancer patient survival. However, analysis of the composition of peripheral immune cells are often limited in retrospective survival studies employing banked blood specimens with long-term follow-up because the application of flow cytometry to such specimens is problematic. The aim of this study was to demonstrate the feasibility of deconvolving blood-based gene expression profiles (GEPs) to estimate the proportions of immune cells and determine their prognostic values for cancer patients.Here, using GEPs from peripheral blood mononuclear cells (PBMC) of 108 non-small cell lung cancer (NSCLC) patients, we deconvolved the immune cell proportions and analyzed their association with patient survival. Univariate Kaplan-Meier analysis showed that a low proportion of T cells was significantly associated with poor patient survival, as was the proportion of T helper cells; however, only the proportion of T cells was independently prognostic for patients by a multivariate Cox regression analysis (hazard ratio = 2.23; 95% CI, 1.01-4.92; p = .048). Considering that altered peripheral blood compositions can reflect altered immune responses within the tumor microenvironment, based on a tissue-based GEPs of NSCLC patients, we demonstrated a significant association between poor patient survival and the low level of antigen presentation, which play a critical role in T cell proliferation.These results demonstrate that it is feasible to deconvolve GEPs from banked blood specimens for retrospective survival analysis of alterations of immune cell composition, and suggest the proportion of T cells in PBMC which might reflect the antigen presentation level within the tumor microenvironment can be a prognostic marker for NSCLC patients.

Cervical lesion grading is critical for effective patient management. A three-tier classification (cervical intraepithelial neoplasia [CIN] grade 1, 2 or 3) based on H&E slide review is widely used. However, for reasons of considerable inter-observer variation in CIN grade assignment and for want of a biomarker validating a three-fold stratification, CAP-ASCCP LAST consensus guidelines recommend a two-tier system: low- or high-grade squamous intraepithelial lesions (LSIL or HSIL). In this study, high-risk HPV E6/E7 and p16 mRNA expression patterns in eighty-six CIN lesions were investigated by RNAscope chromogenic in situ hybridization (CISH). Specimens were also screened by immunohistochemistry for p16INK4a (clone E6H4), and by tyramide-based CISH for HPV DNA. HPV genotyping was performed by GP5+/6+ PCR combined with cycle-sequencing. Abundant high-risk HPV RNA CISH signals were detected in 26/32 (81.3%) CIN 1, 22/22 (100%) CIN 2 and in 32/32 (100%) CIN 3 lesions. CIN 1 staining patterns were typified (67.7% specimens) by abundant diffusely staining nuclei in the upper epithelial layers; CIN 2 lesions mostly (66.7%) showed a combination of superficial diffuse-stained nuclei and multiple dot-like nuclear and cytoplasmic signals throughout the epithelium; CIN 3 lesions were characterized (87.5%) by multiple dot-like nuclear and cytoplasmic signals throughout the epithelial thickness and absence/scarcity of diffusely staining nuclei (trend across CIN grades: P

BACKGROUND: Several studies have reported that the GT dinucleotide repeat length polymorphism and the G2964A polymorphism in signal transducer and activator of transcriptional factor 6 gene are associated with asthma susceptibility, but others have conflicting results. Our meta-analysis aimed to elucidate the emerging paradigms. METHODS: We searched PUBMED, EMBASE, ISI web of knowledge, Chinese National Knowledge Infrastructure, and Wanfang databases. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to evaluate the strength of association. We applied Bonferroni step-down and Benjamini-Hochberg step-up methods to adjust the values for multiple comparisons. RESULTS: A total of 12 individual studies in 11 articles were included in the meta-analysis. For GT repeat polymorphism, the S allele had approximately 45% increased risk of asthma (S vs. L: OR = 1.45, 95% CI = 1.22-1.71, P(UNCORRECTED) < 0.001, P(Bon) < 0.001, P(FDR) < 0.001). Further analysis indicated that GT13 and GT14 contributed to asthma risk, whereas GT15 and GT16 were protective (GT13 vs. GT15: OR = 1.38, 95% CI = 1.16-1.65, P(UNCORRECTED ) = 0.001, P(Bon) = 0.005, P(FDR) = 0.002). Similar results were obtained in the subgroup analysis of Asian population. G2964A polymorphism analysis showed that the AA genotype moderately increased the risk of asthma by 47% compared with the GG genotype (OR = 1.47, p = 0.068) in Chinese population, whereas the 2964A allele moderately increased the risk of asthma in Chinese population by 18% (2964A vs. 2964G: OR = 1.18, p = 0.08). However, none of the associations reached statistically significant levels particularly after correction for multiple testing. CONCLUSIONS: This meta-analysis suggests that S allele (GT13 and GT14) of the GT repeat polymorphism confers significant risks to asthma. However, the G2964A polymorphism does not have an association with the susceptibility to asthma.