Ecological barriers mediate spatiotemporal shifts of bird communities at a continental scale.

Species' range shifts and local extinctions caused by climate change lead to community composition changes. At large spatial scales, ecological barriers, such as biome boundaries, coastlines, and elevation, can influence a community's ability to shift in response to climate change. Yet, ecological barriers are rarely considered in climate change studies, potentially hindering predictions of biodiversity shifts. We used data from two consecutive European breeding bird atlases to calculate the geographic distance and direction between communities in the 1980s and their compositional best match in the 2010s and modeled their response to barriers. The ecological barriers affected both the distance and direction of bird community composition shifts, with coastlines and elevation having the strongest influence. Our results underscore the relevance of combining ecological barriers and community shift projections for identifying the forces hindering community adjustments under global change. Notably, due to (macro)ecological barriers, communities are not able to track their climatic niches, which may lead to drastic changes, and potential losses, in community compositions in the future.

PHOTOLYASE/BLUE LIGHT RECEPTOR2 regulates chrysanthemum flowering by compensating for gibberellin perception.

The gibberellins (GAs) receptor GA INSENSITIVE DWARF1 (GID1) plays a central role in GA signal perception and transduction. The typical photoperiodic plant chrysanthemum (Chrysanthemum morifolium) only flowers when grown in short-day photoperiods. In addition, chrysanthemum flowering is also controlled by the aging pathway, but whether and how GAs participate in photoperiod- and age-dependent regulation of flowering remain unknown. Here, we demonstrate that photoperiod affects CmGID1B expression in response to GAs and developmental age. Moreover, we identified PHOTOLYASE/BLUE LIGHT RECEPTOR2, an atypical photocleavage synthase, as a CRYPTOCHROME-INTERACTING bHLH1 interactor with which it forms a complex in response to short days to activate CmGID1B transcription. Knocking down CmGID1B raised endogenous bioactive GA contents and GA signal perception, in turn modulating the expression of the aging-related genes MicroRNA156 and SQUAMOSA PROMOTER BINDING PROTEIN-LIKE3. We propose that exposure to short days accelerates the juvenile-to-adult transition by increasing endogenous GA contents and response to GAs, leading to entry into floral transformation.

Fabrication and Enzymatic Disorganization of Multiresponse Worm-Like Micelles.

How to fabricate multiresponse worm-like micelles (WLMs) and the corresponding green disposal is still challenging. A strategy of fabricating the surfactant-based WLMs that can respond simultaneously to light, heat, and pH was developed by using triple-response sodium (E)-2-(4-(phenyldiazenyl)phenoxy) acetate (AzoNa) and butyrylcholinesterase (BChE)-hydrolyzable palmitoylcholine bromide (PCB). Under the optimal molar ratio of AzoNa to PCB (∼0.5), the PCB-AzoNa WLMs formed with a maximum zero-shear viscosity (η0) value of about 2.1 × 105 mPa·s and an average diameter (D) of 4.1 ± 0.6 nm under conditions of 37 °C and pH 7.4. After irradiated with 365 nm UV light for 80 min, AzoNa underwent the trans-to-cis transition, by which the PCB-AzoNa WLMs was destroyed; however, the PCB-AzoNa WLMs could be reformed upon the irradiation of 455 nm blue light for 18 h or heating at 70 °C for 45 min due to the cis-to-trans isomerization of AzoNa. When pH changed from 7.4 to 2.0, the PCB-AzoNa WLMs was destroyed rapidly because of the conversion of AzoNa to the acid form of AzoH, whereas the PCB-AzoNa WLMs could be reformed after pH was restored to 7.4. The multiple responsiveness of the PCB-AzoNa WLMs was reversible due to the reversible trans-cis isomerization or protonation of AzoNa. Besides, the average D values of light, heat, and pH-regenerated PCB-AzoNa WLMs were 4.2 ± 0.7, 4.0 ± 0.7, and 4.0 ± 0.6 nm, respectively. Finally, the PCB-AzoNa WLMs could be enzymatically disorganized under conditions of 37 °C and pH 7.4 due to the BChE-catalyzed hydrolysis of PCB. We hope that the fabrication and enzymatic disorganization strategies for PCB-based multiresponse WLMs presented here will find potential applications in the formulation of antimicrobial household and personal care products containing PCB and in the green disposal of viscous waste containing PCB.

CircCOX6A1 suppresses osteogenic differentiation and aggravates osteoporosis via miR-512-3p/DYRK2 axis.

BACKGROUND: Osteoporosis (OP), characterized by compromised bone integrity and increased fracture risk, poses a significant health challenge. Circular RNAs (circRNAs) have emerged as crucial regulators in various pathophysiological processes, prompting investigation into their role in osteoporosis. This study aimed to elucidate the involvement of circCOX6A1 in OP progression and understand its underlying molecular mechanisms. The primary objective was to explore the impact of circCOX6A1 on bone marrow-derived mesenchymal stem cells (BMSCs) and its potential interactions with miR-512-3p and DYRK2. METHODS: GSE161361 microarray analysis was employed to assess circCOX6A1 expression in OP patients. We utilized in vitro and in vivo models, including BMSC cultures, osteogenic differentiation assays, and an OVX-induced mouse model of OP. Molecular techniques such as quantitative RT-PCR, western blotting, and functional assays like alizarin red staining (ARS) were employed to evaluate circCOX6A1 effects on BMSC proliferation, apoptosis, and osteogenic differentiation. The interaction between circCOX6A1, miR-512-3p, and DYRK2 was investigated through dual luciferase reporter assays, RNA immunoprecipitation, and RNA pull-down assays. RESULTS: CircCOX6A1 was found to be upregulated in osteoporosis patients, and its expression inversely correlated with osteogenic differentiation of BMSCs. CircCOX6A1 knockdown enhanced osteogenic differentiation, as evidenced by increased mineralized nodule formation and upregulation of osteogenic markers. In vivo, circCOX6A1 knockdown ameliorated osteoporosis progression in OVX mice. Mechanistically, circCOX6A1 acted as a sponge for miR-512-3p, subsequently regulating DYRK2 expression. CONCLUSION: This study provides compelling evidence for the role of circCOX6A1 in osteoporosis pathogenesis. CircCOX6A1 negatively regulates BMSC osteogenic differentiation through the miR-512-3p/DYRK2 axis, suggesting its potential as a therapeutic target for mitigating OP progression.

Homocysteine modulates CXCL10/CXCR3 axis activity to induce endothelial dysfunction.

Elevated homocysteine (Hcy) levels have been linked to the development of cardiovascular diseases, notably endothelial dysfunction, a critical precursor to atherosclerosis. In this extensive investigation, we explore the intricate pathways through which Hcy influences endothelial dysfunction, with particular attention to the CXCL10/CXCR3 axis. Employing a dual approach encompassing both in vitro and in vivo models, we scrutinize the repercussions of Hcy exposure on endothelial functionality. Our results reveal that Hcy significantly impairs crucial endothelial processes, including cell migration, proliferation, and tube formation. Concomitantly, Hcy upregulates the expression of adhesion molecules, exacerbating endothelial dysfunction. In a murine hyperhomocysteinemia (HHcy) model, we observed a parallel increase in plasma Hcy levels and adverse vascular effects. Moreover, our study unraveled a pivotal role of the CXCL10/CXCR3 axis in Hcy-induced endothelial dysfunction. Hcy exposure led to the upregulation of CXCL10 and CXCR3, both in vitro and in HHcy mice. Importantly, the blockade of this axis, achieved through specific antibodies or NBI-74330, mitigated the detrimental effects of Hcy on endothelial function. In conclusion, our findings illuminated the central role of the CXCL10/CXCR3 axis in mediating Hcy-induced endothelial dysfunction, providing valuable insights for potential therapeutic strategies in managing HHcy-related cardiovascular diseases.

Dietary carotenoids intake and sex differences in relation to chronic kidney disease a cross-sectional assessment in the NHANES study.

BACKGROUND AND AIMS: Current evidence on the relationship between dietary carotenoids intake (DCI) and chronic kidney disease (CKD) are limited. Moreover, whether there is an association between DCI and prevalence of CKD and how this association might be impacted by sex is not clear. METHODS AND RESULTS: Overall, 4507 women and 4396 men were included for analysis. The study used data from the National Health and Nutrition Examination Survey (NHANES), a cross-sectional survey carried out in the USA. The exposure factor for this analysis was DCI. The outcome was CKD, defined as eGFR < 60mL/min/1.73 m2. Multivariate logistic regression was used to analyzed the associations of DCI and prevalence of CKD both in men and women. There was a significant inverse association between higher DCI and prevalence of CKD only among females. Per LgDCI unit increment, the multivariable adjusted odd ratio (OR) (95% confidence interval) for prevalence of CKD was 0.72 (0.58, 0.90) in females and 0.95 (0.77, 1.18) in males. When compared with the lowest quartile, the ORs of the highest quartile of DCI for prevalence of CKD were 0.59 (0.40, 0.87) in females and 0.87 (0.60, 1.26) in males. The associations remained similar in the subgroup analyses. CONCLUSIONS: The findings suggest that a higher intake of dietary carotenoids is associated with a lower prevalence of CKD in women, but not in men.

Preoperative supine pelvic incidence predicts standing pelvic incidence following S2AI fixation in patients with adult spinal deformity: a prospective study.

STUDY DESIGN: A prospective study. OBJECTIVE: The aim of this study was to investigate the PI change in different postures and before and after S2­alar­iliac (S2AI) screw fixation, and to investigate whether pre-op supine PI could predict post-op standing PI. Previous studies have reported PI may change with various positions. Some authors postulated that the unexpected PI change in ASD patients could be due to sacroiliac joint laxity, S2-alar-iliac (S2AI) screw placement, or aggressive sagittal cantilever technique. However, there was a lack of investigation on how to predict post-op standing PI when making surgical strategy. METHODS: A prospective case series of ASD patients undergoing surgical correction with S2AI screw placement was conducted. Full-spine X-ray films were obtained at pre-op standing, pre-op supine, pre-op prone, as well as post-op standing postures. Pelvic parameters were measured. Spearman correlation analysis was used to determine relationships between each parameter. RESULTS: A total of 83 patients (22 males, 61females) with a mean age of 58.4 ± 9.5 years were included in this study. Pre-op standing PI was significantly lower than post-op standing PI (p = 0.004). Pre-op prone PI was significantly lower than post-op standing PI (p = 0.001). By contrast, no significant difference was observed between pre-op supine and post-op standing PI (p = 0.359) with a mean absolute difference of 2.2° ± 1.9°. Correlation analysis showed supine PI was significantly correlated with post-op standing PI (r = 0.951, p < 0.001). CONCLUSION: This study revealed the PI changed after S2AI screw fixation. The pre-op supine PI can predict post-op standing PI precisely, which facilitates to provide correction surgery strategy with a good reference for ideal sagittal alignment postoperatively.

Potential impairment of spinal cord around the apical vertebral level in hyperkyphotic patients: findings from diffusion tensor imaging.

PURPOSE: To evaluate the neuronal metrics/microstructure of the spinal cord around apical region in patients with hyperkyphosis using diffusion tensor imaging (DTI). METHODS: Thirty-seven patients with hyperkyphosis aged 45.5 ± 19.6 years old who underwent 3.0 T magnetic resonance imaging (MRI) examination with DTI sequence were prospectively enrolled from July 2022 to July 2023. Patients were divided into three groups according to spinal cord/ cerebrospinal fluid (CSF) architecture on sagittal-T2 MRI of the thoracic apex (the axial spinal cord classification): Group A-circular cord with visible CSF, Group B-circular cord without visible CSF at apical dorsal, and Group C-spinal cord deformed without intervening CSF. The fractional anisotropy (FA) values acquired from DTI were compared among different groups. Correlations between DTI parameters and global kyphosis (GK)/sagittal deformity angular ratio (sagittal DAR) were evaluated using Pearson correlation coefficients. RESULTS: In all patients, FA values were significantly lower at apical level as compared with those at one level above or below the apex (0.548 ± 0.070 vs. 0.627 ± 0.056 versus 0.624 ± 0.039, P < 0.001). At the apical level, FA values were significantly lower in Group C than those in Group B (0.501 ± 0.052 vs. 0.598 ± 0.061, P < 0.001) and Group A (0.501 ± 0.052 vs. 0.597 ± 0.019, P < 0.001). Moreover, FA values were significantly lower in symptomatic group than those in non-symptomatic group (0.498 ± 0.049 v. 0.578 ± 0.065, P < 0.001). Pearson correlation analysis showed that GK (r2 = 0.3945, P < 0.001) and sagittal DAR (r2 = 0.3079, P < 0.001) were significantly correlation with FA values at apical level. CONCLUSION: In patients with hyperkyphosis, the FA of spinal cord at apical level was associated with the neuronal metrics/microstructure of the spinal cord. Furthermore, the DTI parameter of FA at apical level was associated with GK and sagittal DAR.

Chrysanthemum MAF2 regulates flowering by repressing gibberellin biosynthesis in response to low temperature.

Chrysanthemum (Chrysanthemum morifolium) is well known as a photoperiod-sensitive flowering plant. However, it has also evolved into a temperature-sensitive ecotype. Low temperature can promote the floral transition of the temperature-sensitive ecotype, but little is known about the underlying molecular mechanisms. Here, we identified MADS AFFECTING FLOWERING 2 (CmMAF2), a putative MADS-box gene, which induces floral transition in response to low temperatures independent of day length conditions in this ecotype. CmMAF2 was shown to bind to the promoter of the GA biosynthesis gene CmGA20ox1 and to directly regulate the biosynthesis of bioactive GA1 and GA4 . The elevated bioactive GA levels activated LEAFY (CmLFY) expression, ultimately initiating floral transition. In addition, CmMAF2 expression in response to low temperatures was directly activated by CmC3H1, a CCCH-type zinc-finger protein upstream. In summary, our results reveal that the CmC3H1-CmMAF2 module regulates flowering time in response to low temperatures by regulating GA biosynthesis in the temperature-sensitive chrysanthemum ecotype.

The exploration of B cell maturation antigen expression in plasma cell dyscrasias beyond multiple myeloma.

BACKGROUND: B cell maturation antigen (BCMA) targeted immunotherapies have demonstrated remarkable clinical efficacy in multiple myeloma (MM). Here, we evaluated the BCMA expression in MM and other plasma cell dyscrasias (PCDs), hoping to provide a potential treatment strategy for the relapsed/refractory PCDs besides MM. METHODS: From January 2018 to August 2021, 377 patients with PCDs were enrolled in this study, including 334 MM, 21 systemic light chain amyloidosis (AL), 5 POEMS syndrome, 14 monoclonal gammopathy of undetermined significance (MGUS), and three monoclonal gammopathy of renal significance (MGRS). The membrane-bound BCMA expression measured by multiparameter flow cytometry was defined by BCMA positivity rate and the mean fluorescence intensity (MFI). RESULTS: The patients with MM had a median BCMA positive rate of 88.55% (range, 0.2% - 99.9%) and median BCMA MFI of 1281 (range, 109 - 48586). While the median BCMA positive rate in other PCDs was 55.8% (6.2% -98.9%), and the median BCMA MFI was 553 (182- 5930). BCMA expression level was negatively associated with hemoglobin concentration in multivariate analysis in terms of BCMA positive rate and MFI. CONCLUSIONS: In conclusion, BCMA has the potential to be a therapeutic target for other PCDs besides MM.

Habitat loss exacerbates pathogen spread: An Agent-based model of avian influenza infection in migratory waterfowl.

Habitat availability determines the distribution of migratory waterfowl along their flyway, which further influences the transmission and spatial spread of avian influenza viruses (AIVs). The extensive habitat loss in the East Asian-Australasian Flyway (EAAF) may have potentially altered the virus spread and transmission, but those consequences are rarely studied. We constructed 6 fall migration networks that differed in their level of habitat loss, wherein an increase in habitat loss resulted in smaller networks with fewer sites and links. We integrated an agent-based model and a susceptible-infected-recovered model to simulate waterfowl migration and AIV transmission. We found that extensive habitat loss in the EAAF can 1) relocate the outbreaks northwards, responding to the distribution changes of wintering waterfowl geese, 2) increase the outbreak risk in remaining sites due to larger goose congregations, and 3) facilitate AIV transmission in the migratory population. In addition, our modeling output was in line with the predictions from the concept of "migratory escape", i.e., the migration allows the geese to "escape" from the location where infection risk is high, affecting the pattern of infection prevalence in the waterfowl population. Our modeling shed light on the potential consequences of habitat loss in spreading and transmitting AIV at the flyway scale and suggested the driving mechanisms behind these effects, indicating the importance of conservation in changing spatial and temporal patterns of AIV outbreaks.

Mutations in immunodeficiency-related genes may increase the risk of infection after CAR-T-cell therapy: a report of two cases.

BACKGROUND: Chimeric antigen receptor T-cell therapy (CAR-T) has yielded unprecedented efficacy in B-cell malignancies. With the increasing use of CAR-T-cell therapy, infection has become one of the major concerns after CAR-T-cell infusion. Some patients even develop refractory or recurrent infections, posing challenges in treatment, prophylactic, and monitoring strategies. However, the mechanisms underlying the development of these infections were not clear. CASE PRESENTATION: We report two cases of infection after CAR-T-cell therapy. Patient 1, diagnosed with multiple myeloma, received anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T)-cell therapy. He developed a refractory urinary infection lasting for over 5 weeks, which was caused by Candida albicans. Whole-exome sequencing revealed that he had an IL-17RA gene mutation. Patient 2, diagnosed with acute lymphoblastic B-cell leukaemia, received anti-CD19 and anti-CD22 CAR-T-cell cocktail therapy and remained in complete remission for over 4 years. The patient had pneumonia five times during the 4 years. Whole-exon sequencing revealed that he had a CX3CR1 gene mutation. CONCLUSION: For patients who develop persistent or recurrent infections after CAR-T-cell therapy, it is recommended to screen for immunodeficiency-related gene mutations, and the results may contribute to the management of infections post-CAR-T treatment.

Nonlinear Frequency Offset Beam Design for FDA-MIMO Radar.

The beam pattern of frequency diversity array (FDA) radar has a range-angle two-dimensional degree of freedom, which makes it possible to distinguish different targets from the same angle and brings a new approach to anti-jamming of radars. However, the beam pattern of conventional linearly frequency-biased FDA radar is range-angle-coupled and time-varying. The method of adding nonlinear frequency bias among the array elements of the FDA array has been shown to eliminate this coupling property while still allowing for better beam performance of the emitted beam. In this paper, we obtain a decoupled and time-invariant beam direction map using the FDA-multi-input-multi-output (FDA-MIMO) radar scheme and then obtain a sharp pencil-shaped main sphere beam pattern with range-angle dependence using a linear frequency offset scheme weighted by a Chebyshev window. Finally, the anti-interference performance of the proposed method is verified in an anti-interference experiment.

[Relationship of Cognitive Function With Menarche Age,Menopause Age, and Reproductive Period in Female Patients With Hypertension].

Objective To explore the relationship of menarche age,menopause age,and reproductive period with cognitive function in the female patients with hypertension.Methods Hypertension screening was carried out in Wuyuan county of Jiangxi province from July to August in 2018.Data were collected through a face-to-face questionnaire survey,physical measurement,and biochemical tests.The cognitive function was scored according to the mini-mental state examination(MMSE)scale.Multiple linear regression and Logistic regression were employed to analyze the effects of menarche age,menopause age,and reproductive period on cognitive function,and the penalized spline regression to fit the curves.Results A total of 4595 postmenopausal women with hypertension were included in the analysis,with the mean age of(65.1±8.4)years,mean menarche age of(16.6±2.2)years,mean menopause age of(48.2±5.0)years,mean reproductive period of(31.7±5.5)years,mean MMSE score of(19.0±6.3)points,and total cognitive impairment detection rate of 40.4%(1859/4595).The detection rates of cognitive impairment were 28.4%,39.1%,and 45.8% in the females with the menarche ages of <15,15-16,and ≥17 years,47.9%,39.7%,and 38.3% in the females with the menopausal ages of <45,45-49,and ≥50 years,and 56.0%,44.4%,40.6%,and 32.6% in the females with the reproductive periods of <25,25-29,30-34,and ≥35 years,respectively.Moreover,the detection rates of cognitive impairment among different age groups were statistically significant(all P<0.05).Compared with the group with the menarche age <15 years,the groups with the menarche ages of 15-16 years and ≥17 years showed increased detection rates of cognitive impairment(OR=1.45,95%CI=1.19-1.75,P<0.001;OR=1.65,95%CI=1.37-1.98,P<0.001).Compared with the group with the menopausal age <45 years,the groups with the menopausal ages of 45-49 years and ≥50 years showed decreased detection rates of cognitive impairment(OR=0.80,95%CI=0.66-0.95,P=0.013;OR=0.78,95%CI=0.65-0.93,P<0.001).Compared with the group with the reproductive period <25 years,the groups with the reproductive periods of 25-29,30-34,and ≥35 years showed decreased detection rates of cognitive impairment(OR=0.66,95%CI=0.52-0.84,P<0.001;OR=0.62,95%CI=0.50-0.76,P<0.001;OR=0.51,95%CI=0.41-0.63,P<0.001).Conclusion The detection rate of cognitive impairment had a positive correlation with menarche age and negative correlations with menopause age and reproductive period in the female patients with hypertension.

CmHY5 functions in apigenin biosynthesis by regulating flavone synthase II expression in chrysanthemum flowers.

MAIN CONCLUSION: The predominant flavones in the ray florets of chrysanthemum flowers are apigenin and its derivatives. CmHY5 participates in apigenin biosynthesis by directly regulating the expression of FNSII-1 in chrysanthemum. Chrysanthemum (Chrysanthemum morifolium) flowers have been used for centuries as functional food and in herbal tea and traditional medicine. The chrysanthemum flower contains significant amounts of the biologically active compound flavones, which has medicinal properties. However, the mechanism regulating flavones biosynthesis in chrysanthemum flowers organs is still unclear. Here, we compared the transcriptomes and metabolomes of different floral organs between two cultivars with contrasting flavone levels in their flowers. We identified 186 flavonoids by metabolome analysis. The predominant flavones in the ray florets of chrysanthemum flowers are apigenin and its derivatives, of which the contents are highly correlated with the expression of flavones synthase II gene CmFNSII-1. We also determined that CmHY5 is a direct upstream regulator of CmFNSII-1 transcription. We showed that CmHY5 RNAi interference lines in chrysanthemum have lower contents of apigenin compared to wild-type chrysanthemum. Our results demonstrated that CmHY5 participates in flavone biosynthesis by directly regulating the expression of FNSII-1 in chrysanthemum.

The chrysanthemum DEAD-box RNA helicase CmRH56 regulates rhizome outgrowth in response to drought stress.

Plants have evolved complex mechanisms to reprogram growth in response to drought stress. In herbaceous perennial plant species, the rhizome, which is normally an organ for propagation and food storage, can also support plant growth in stressful environments, and allows the plant to perennate and survive stress damage. However, the mechanisms that regulate rhizome growth in perennial herbs during abiotic stresses are unknown. Here, we identified a chrysanthemum (Chrysanthemum morifolium) DEAD-box RNA helicase gene, CmRH56, that is specifically expressed in the rhizome shoot apex. Knock down of CmRH56 transcript levels decreased the number of rhizomes and enhanced drought stress tolerance. We determined that CmRH56 represses the expression of a putative gibberellin (GA) catabolic gene, GA2 oxidase6 (CmGA2ox6). Exogenous GA treatment and silencing of CmGA2ox6 resulted in more rhizomes. These results demonstrate that CmRH56 suppresses rhizome outgrowth under drought stress conditions by blocking GA biosynthesis.

CircRNA VIM silence synergizes with sevoflurane to inhibit immune escape and multiple oncogenic activities of esophageal cancer by simultaneously regulating miR-124/PD-L1 axis.

BACKGROUND: Circular RNA of vimentin (circ-VIM) is a predictor for poor prognosis of acute myeloid leukemia, but we had little information on its function in esophageal cancer (EC). Here we examined the effects of circ-VIM together with sevoflurane on immune escape and multiple oncogenic activities of EC. METHODS: Bioinformatic tools, luciferase assay, and RNA immunoprecipitation were used to examine regulations between circ-VIM, miR-124-3p (miR-124), and PD-L1. CCK-8, wound healing, and Transwell assays were used to measure cell proliferation, migration, and invasion, respectively. The impacts of EC cells on cytotoxicity, proliferation, and apoptosis of CD8+ T cells were examined using LDH assay, CFSE staining, and Annexin V/PI staining, respectively. The in vivo tumorigenesis and lung metastases were assessed using xenograft model and tail vein injection of EC cells. RESULTS: Significant upregulation of circ-VIM and PD-L1 and downregulation of miR-124 were detected in EC tissues or cells. Circ-VIM sponged miR-124 and released its suppression on the downstream target PD-L1. Sevoflurane, independent of circ-VIM, also upregulated miR-124 to lower PD-L1 expression. By modulating miR-124/PD-L1 axis, silencing circ-VIM and applying sevoflurane both inhibited immune escape and multiple oncogenic activities of EC in vitro, and suppressed xenograft growth and lung metastases in vivo. The inactivation of Ras/ERK signaling pathway was involved in suppression of malignant phenotypes by silencing circ-VIM and sevoflurane treatment. CONCLUSIONS: Silencing circ-VIM and applying sevoflurane, by separately regulating miR-124/PD-L1 axis, presented synergistic effects in inhibiting immune escape and multiple malignant phenotypes of EC cells.

Range shifts of overwintering birds depend on habitat type, snow conditions and habitat specialization.

Climatic warming is forcing species to shift their ranges poleward, which has been demonstrated for many taxa globally. Yet, the influence of habitat types on within- and among-species variations of distribution shifts has rarely been studied, especially during the non-breeding season. Here, we investigated habitat-specific shift distances of northern range margins and directions of the distribution center based on long-term data of overwintering birds in Finland. Specifically, we explored influences of habitat type, species' snow depth tolerance, species' climatic niche and habitat specialization on range shifts during the past 40 years in 81 bird species. Birds overwintering in arable land shifted more clearly toward north compared to birds of the same species in rural and forest habitats, while the northern range margin shift distances did not significantly differ among the habitat types. Range shifts were more linked with the species' snow depth tolerance rather than species' climatic niche. Snow depth tolerance of species was negatively associated with the eastward shift direction across all habitats, while we found habitat-specific patterns with snow depth for northward shift directions and northern margin shift distances. Species with stronger habitat specializations shifted more strongly toward north as compared to generalist species, whereas the climatic niche of bird species only marginally correlated with range shifts, so that cold-dwelling species shifted longer distances and more clearly eastward. Our study reveals habitat-specific patterns linked to snow conditions for overwintering boreal birds and highlights the importance of habitat availability and preference in climate driven range shifts.

Selection of the optimal distal fusion level for Scheuermann kyphosis with different curve patterns: when can we stop above the sagittal stable vertebra?

PURPOSE: To investigate the optimal lowest instrumented vertebra (LIV) in the treatment of Scheuermann kyphosis (SK) with different curve patterns. METHODS: Fifty-two SK patients who underwent posterior surgery between January 2010 and December 2017 with a minimum follow-up of 2 years were retrospectively reviewed. Patients were divided into two groups based on the curve pattern: the Scheuermann thoracic kyphosis (STK group) or Scheuermann thoracolumbar kyphosis (STLK group). Based on the relationship between the sagittal stable vertebra (SSV) and LIV, both groups were further divided into the SSV group and SSV-1 group. Radiographic parameters, distal junctional kyphosis (DJK) incidence and SRS-22 questionnaire scores were evaluated. RESULTS: In STK and STLK groups, there were no significant differences in most pre- and postoperative radiographic assessments between SSV and SSV-1 subgroups. DJK incidence showed no significant differences between groups during follow-up (P > 0.05). LIV-PSVL was significantly more negative in the SSV-1 group than that in the SSV group (P < 0.001). Within the SSV-1 group, patients with DJK showed a more negative LIV-PSVL (P = 0.039). Moderate correlation was observed between preoperative LIV-PSVL and DJK with a Spearman coefficient of - 0.474 (P = 0.035). Receiver operative characteristic curve analysis showed that the threshold value of preoperative LIV-PSVL to predict DJK was - 37.35 mm (area under the curve 0.882). CONCLUSION: Shorter fusion stopping at SSV-1 achieved comparable clinical outcomes and did not increase the risk of DJK for both STK and STLK patients. For patients whose preoperative LIV-PSVL < - 37.35 mm, extending fusion to SSV is an acceptable solution to prevent DJK.

Dynamic change of pelvic incidence after long fusion to pelvis with S2-alar-iliac screw: a 2-year follow-up study.

INTRODUCTION: Pelvic incidence (PI) is a key morphological parameter that reflects the relation between the sacrum and iliac wings. It is well accepted that PI remains constant after reaching maturity. However, recent studies indicated that PI might be altered after lumbosacral fusion. Additionally, it remains uncertain on the long-term influence of long fusion to pelvis with S2-alar-iliac screw on PI in patients with adult spinal deformity (ASD). STUDY DESIGN: A retrospective study. OBJECTIVE: To investigate whether and how PI would change during the follow-up in ASD patients who underwent S2AI fixation and to identify factors associated with the change in PI. METHODS: We retrospectively reviewed all ASD patients who underwent spinal surgery using S2AI screws between November 2014 and January 2017 at our institution. Patients with minimum follow-up of two years were included. The following sagittal radiographic parameters were measured: PI, Lumbar lordosis (LL), pelvic tilt (PT), PI-LL, sagittal vertical axis (SVA) at pre-op, post-op and 2-year follow-up. According to the changes in PI at immediate post-operation, patients were classified into two groups; Group A: Changes of PI less than or equal 5° and Group B: Changes of PI greater than 5°. RESULTS: A total of 82 ASD patients (Group A: 32, Group B: 50; mean age of 53.5 ± 12.6 years) with a mean follow-up period of 30.2 ± 9.2 months were included in this study. At immediate post-operation, Group A showed no significant change in PI (45.7° ± 11.4° to 45.3° ± 11.2°, p = 0.749); while Group B had a significant decrease in PI (51.6° ± 14.5° to 40.9° ± 14.0°, p < 0.001). At the last follow-up, 48% patients (24/50) in Group B had a significant increase in PI (32.8° ± 6.4° to 45.8° ± 11.2°, p < 0.001). Intergroup analysis showed that ΔPI, post-op PI, post-op PT and age were significantly different between both groups. In addition, pre-op PI, post-op PI, post-op PT, post-op PI-LL were significantly correlated with ΔPI at last follow-up. Also, logistic regression analysis showed that post-op PI was the associated risk factor (OR = 0.865, p = 0.024) for PI-LL mismatch. CONCLUSION: Our study showed that PI decreased in more than half of ASD patients immediately after spinal surgery using S2AI screws. Approximately 48% of them were able to recover during the 2-year follow-up. Lower pre-op PI, post-op PI and PT were found to be strongly associated with the return of PI. Thus, these current findings indicated that patients with a high PI at pre-operation should not be over-corrected to avoid PI-LL mismatch postoperatively.