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Immovable cultural heritages are nonrenewable and irreplaceable excellent cultural resources. With the help of the GIS spatial analysis method, Geodetector and location entropy, this paper explores the spatial and temporal distribution characteristics and influencing factors of 1070 nationally and provincially designated immovable cultural heritage sites in Hubei, China. The physical geographical factors, historical and humanistic factors, and their explanatory power indexes are constructed, which provide a scientific quantitative analysis of influencing factors for the spatial distribution of cultural heritages. The results show that the kernel density distribution of immovable cultural heritages in Hubei Province is agglomeration, and Wuhan is the dominant nuclear. The number of cultural heritages in different historical periods is unevenly distributed. The average center of cultural heritages in each period was located in Jingshan. The spatial differentiation of these cultural heritages is affected by multiple factors. Among natural factors, topographic and geomorphic factors such as elevation and slope have a more significant effect, whereas among social and economic factors, the cultural atmosphere and the number of permanent residents have the most significant explanatory power. These findings may help local governments formulate more effective measures for the protection of immovable cultural heritages.

The marine diatom Phaeodactylum tricornutum is a polymorphological, ecologically significant, and well-studied model of unicellular microalga. This diatom can accumulate diverse important metabolites. Herein, we cultured P. tricornutum in an internally installed tie-piece flat-plate photobioreactor under 14.5 m mol L^-1（high nitrogen, HN） and 2.9 m mol L^-1（low nitrogen, LN） of KNO_3 and assessed its time-resolved changes in biochemical compositions. The results showed that HN was inductive to accumulate high biomass（4.1 g L^-1）. However, the LN condition could accelerate lipid accumulation in P. tricornutum. The maximum total lipid（TL） content under LN was up to 42.5% of biomass on day 12. Finally, neutral lipids（NLs） were 63.8% and 75.7% of TLs under HN and LN, respectively. The content of EPA ranged from 2.3% to 1.5% of dry weight during the growth period under the two culture conditions. Peak volumetric lipid productivity of 128.4 mg L^-1d^-1 was achieved in the HN group（on day 9）. The highest volumetric productivity values of EPA, chrysolaminarin, and fucoxanthin were obtained in the exponential phase（on day 6） under HN, which were 9.6, 93.6, and 4.7 mg L^-1d^-1, respectively. In conclusion, extractable amounts of lipids, EPA, fucoxanthin, and chrysolaminarin could be obtained from P. tricornutum by regulating the culture conditions.

Parental care in birds consists of elaborate forms across stages, including nest building, incubation, and offspring provision. Despite their evolutionary importance, knowledge gaps exist in the extent to which parents contribute disproportionately to these forms and factors that are associated with variations in care patterns between sexes. Here, we analyzed 1533 bird species and discovered remarkable variability in care patterns. We show that parental care should not be viewed as a unitary trait but rather as a set of integrated features that exhibit considerable temporal and sex-specific variation. Our analyses also reveal moderate consistency in care patterns between breeding stages, pointing towards shared intrinsic factors driving sex-specific care. Notably, we found that species experiencing strong sexual selection on males or species facing paternity uncertainty display a tendency towards female-biased care. This work advances our understanding of the temporal variations in sex-specific contributions to avian parental care and their potential evolutionary drivers. Parental care in birds includes diverse behaviours but the variation in care from each parent across the breeding cycle and between species is unclear. Here, the authors study 1533 bird species, finding different patterns across breeding stages, and that species with strong sexual selection or paternity uncertainty tend to show female-biased care.

The uplift of the Qinghai-Tibet Plateau is one of the greatest geological events on Earth, pivotally shaping biogeographic patterns across continents, especially for migratory species that need to overcome topographical barriers to fulfil their annual circle. However, how the uplift influences animal migration strategies remains largely unclear. We compare the current flyways of 50 avian species migrating across the plateau with those reconstructed before the uplift as a counterfactual. We find that the major effect of the plateau uplift is changing avian migratory directions from the latitudinal to the longitudinal. The monsoon system generated by the uplift rather than the high elevation per se shapes those changes. These findings unveil how an important global geological event has influenced biogeographic patterns of migratory birds, yielding testable hypotheses for how observed avian distributions emerge.

Objective This study aimed to build and validate a nomogram model to predict the risk of incomplete immune reconstitution in people living with HIV (PLWH). Methods Totally 3783 individuals with a confirmed diagnosis of HIV/AIDS were included. A predictive model was developed based on a retrospective set ( N  = 2678) and was validated using the remaining cases ( N  = 1105). Univariate and multivariate logistic regression analyses were performed to determine valuable predictors among the collected clinical and laboratory variables. The predictive model is presented in the form of a nomogram, which is internally and externally validated with two independent datasets. The discrimination of nomograms was assessed by calculating the area under the curve (AUC). Besides, calibration curve and decision curve (DCA) analyses were performed in the training and validation sets. Results The final model comprised 5 predictors, including baseline CD4, age at ART initiation, BMI, HZ and TBIL. The AUC of the nomogram model was 0.902, 0.926, 0.851 in the training cohort, internal validation and external cohorts. The calibration accuracy and diagnostic performance were satisfactory in both the training and validation sets. Conclusions This predictive model based on a retrospective study was externally validated using 5 readily available clinical indicators. It showed high performance in predicting the risk of incomplete immune reconstitution in people living with HIV.

BackgroundGlioblastoma (GBM) treatment is undermined by the suppressive tumor immune microenvironment (TIME). Seek for effective methods for brain TIME modulation is a pressing need. However, there are two major challenges against achieving the goal: first, to screen the effective drugs with TIME-remodeling functions and, second, to develop a brain targeting system for delivering the drugs.MethodsIn this study, an α7 nicotinic acetylcholine receptors (nAChRs)-binding peptide DCDX was used to modify the codelivery liposomes to achieve a ‘three-birds-one-stone’ delivery strategy, that is, multi-targeting the glioma vessel endothelium, glioma cells, and tumor-associated macrophages that all overexpressed α7 nAChRs. A brain-targeted liposomal honokiol and disulfiram/copper codelivery system (CDX-LIPO) was developed for combination therapy via regulating mTOR (mammalian target of rapamycin) pathway for remodeling tumor metabolism and TIME. Honokiol can yield a synergistic effect with disulfiram/copper for anti-GBM.ResultsIt was demonstrated that CDX-LIPO remarkably triggered tumor cell autophagy and induced immunogenic cell death, and meanwhile, activated the tumor-infiltrating macrophage and dendritic cells, and primed T and NK (natural killer) cells, resulting in antitumor immunity and tumor regression. Moreover, CDX-LIPO promoted M1-macrophage polarization and facilitated mTOR-mediated reprogramming of glucose metabolism in glioma.ConclusionThis study developed a potential combinatory therapeutic strategy by regulation of TIME and a ‘three-birds-one-stone’-like glioma-targeting drug delivery system.

Global Navigation Satellite System (GNSS) tomography has developed into an efficient tool for sensing the high spatiotemporal variability of atmospheric water vapor. The integration of GNSS top signals and side rays for tropospheric tomography systems using a novel height factor model (HFM) is proposed and discussed in this paper. Within the HFM, the sectional slant wet delay (SWD) of inside signals (the part of the side signal inside the tomography area), which is considered a key factor for modeling side rays, is separated into isotropic and anisotropic components. Correspondingly, two height factors are defined to calculate the isotropic and anisotropic part of tropospheric delays in the HFM. In addition, the dynamic tomography top boundary is first analyzed and determined based on 30-year radiosonde data to reasonably divide signals into top and side rays. Four special experimental schemes based on different tomography regions of Hong Kong are performed to assess the proposed HFM method, the results of which show increases of 33.42% in the mean utilization of rays, as well as decreases of 0.46 g/m3 in the average root mean square error (RMSE), compared to the traditional approach, revealing the improvement of tomography solutions when the side signals are included in the modeling. Furthermore, compared with the existing correction model for modeling side rays, the water vapor profiles retrieved from the proposed improved model are closer to the radiosonde data, which highlights the advantages of the proposed HFM for optimizing the GNSS tomography model.

Background Mesenchymal stem cells (MSCs) are the most promising cell types for bone regeneration and repair due to their osteogenic potential. MSC differentiation is precisely regulated and orchestrated by the mechanical and molecular signals from the extracellular environment, involving complex pathways regulated at both the transcriptional and post-transcriptional levels. However, the potential role of long noncoding RNA (lncRNA) in the osteogenic differentiation of human MSCs remains largely unclear. Methods Here, we undertook the survey of differential coding and noncoding transcript expression profiling and functional network analysis during osteogenic differentiation of human bone marrow mesenchymal stem cells (BMSCs) using human whole transcriptome microarray. The key pathways, mRNAs, and lncRNAs controlling osteogenic differentiation of BMSCs were identified by further bioinformatic analysis. The role of lncRNA in the osteogenic differentiation of MSCs was verified by lncRNA overexpression or knockdown methods. Results A total of 1269 coding transcripts with 648 genes significantly upregulated and 621 genes downregulated, and 1408 lncRNAs with 785 lncRNAs significantly upregulated and 623 lncRNAs downregulated were detected along with osteogenic differentiation. Bioinformatic analysis identified that several pathways may be associated with osteogenic differentiation potentials of BMSCs, such as the MAPK signaling pathway, the Jak-STAT signaling pathway, the Toll-like receptor signaling pathway, and the TGF-beta signaling pathway, etc. Bioinformatic analysis also revealed 13 core regulatory genes including seven mRNAs (GPX3, TLR2, BDKRB1, FBXO5, BRCA1, MAP3K8, and SCARB1), and six lncRNAs (XR_111050, NR_024031, FR374455, FR401275, FR406817, and FR148647). Based on the analysis, we identified one lncRNA, XR_111050, that could enhance the osteogenic differentiation potentials of MSCs. Conclusions The potential regulatory mechanisms were identified using bioinformatic analyses. We further predicted the interactions of differentially expressed coding and noncoding genes, and identified core regulatory factors by co-expression networks during osteogenic differentiation of BMSCs. Our results could lead to a better understanding of the molecular mechanisms of genes and lncRNAs, and their cooperation underlying MSC osteogenic differentiation and bone formation. We identified that one lncRNA, XR_111050, could be a potential target for bone tissue engineering.

White matter hyperintensities (WMHs) are key neuroimaging markers of cerebral small vessel diseases. This study aimed to investigate whether intracranial and extracranial atherosclerotic stenosis is associated with WMHs. Following a previously registered protocol (PROSPERO protocol: CRD42023407465), PubMed, Web of Science, and Embase were systematically searched for relevant literature published until March 2023. Cross-sectional studies examining the association between intracranial and extracranial atherosclerotic stenosis and WMHs were included. Random effects models were used to calculate the pooled estimates. Twenty-one eligible studies, including 10,841 participants, were identified. Intracranial and extracranial atherosclerotic stenosis was associated with an increased risk of WMHs (OR 1.80, 95% CI 1.25-2.57,  = 75%) and increased WMH volumes (SMD 0.40, 95% CI 0.18-0.63,  = 63%). Heterogeneity resulted from the WMHs rating method and the location. Extracranial atherosclerotic stenosis (ECAS) was significantly associated with WMHs (OR 2.10, 95% CI 1.22-3.62,  = 71%), but intracranial atherosclerotic stenosis (ICAS) was insignificantly associated with WMHs (OR 1.75, 95% CI 0.97-3.15,  = 84%). The association was stable in the subgroup analysis based on WMHs location, which included deep WMHs and periventricular WMHs. Intracranial and extracranial atherosclerotic stenosis is associated with WMHs. This association is significant in ECAS, but attenuated in ICAS.

Background: There have been contradictory findings regarding the relationship between serum uric acid levels and prognosis in acute ischemic stroke. Whether this association is nonlinear due to uric acid's paradoxical properties (antioxidant and prooxidant) is unclear. Methods: We searched PubMed, Web of Science, and Embase databases until December 2022. Cohort studies reporting serum uric acid levels and functional outcome, mortality, or neurological complications in patients with acute ischemic stroke were included. Summary effect estimates were calculated using a random-effect model. Moreover, dose-response relationships were assessed by the generalized least squares trend estimation. Results: Altogether, 13 cohort studies were identified in this study. Compared to the lowest baseline serum uric acid levels, the highest levels were associated with decreased risk of poor functional outcome (OR = 0.70, 95% CI 0.54–0.91, I2 = 29%), hemorrhagic transformation (OR = 0.15, 95% CI 0.05–0.42, I2 = 79%), and post-stroke depression (OR = 0.04, 95% CI 0.00–0.95, I2 = 89%), but not associated with mortality and symptomatic intracerebral hemorrhage. A nonlinear relationship was observed in poor functional outcome (U-shaped, P for nonlinearity = 0.042), hemorrhagic transformation (inverse, P for nonlinearity = 0.001), and post-stroke depression (inverse, P for nonlinearity = 0.002). In addition, there was a single study reporting a U-shaped association in post-stroke epilepsy (P for nonlinearity < 0.001). Furthermore, another study reported a positive curvilinear association in stroke recurrence (P for nonlinearity < 0.05). The insufficient number of original articles for some prognostic indicators should be considered when interpreting the results of this meta-analysis. Conclusions: In patients with acute ischemic stroke, serum uric acid levels are nonlinearly associated with the risk of poor functional outcome (U-shaped). More evidence is needed to confirm the association between serum uric acid levels and neurological complications following acute ischemic stroke.