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Abstract Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.

Abstract This study explores the hot deformation behavior of Al–Zn–Mg–Cu alloy through uniaxial hot compression (200 °C–450°C) using the Gleeble-1500. True stress–strain curves were corrected, and three models were established: the Arrhenius model, strain compensated (SC) Arrhenius model, and strain compensated recrystallization temperature (RT) segmentation-based (TS-SC) Arrhenius model. Comparative analysis revealed the limited predictive accuracy of the SC Arrhenius model, with a 25.12% average absolute relative error (AARE), while the TS-SC Arrhenius model exhibited a significantly improved to 9.901% AARE. Material parameter calculations displayed variations across the temperature range. The SC Arrhenius model, utilizing an average slope method for parameter computation, failed to consider temperature-induced disparities, limiting its predictive capability. Hot processing map, utilizing the Murty improved Dynamic Materials Model (DMM), indicated optimal conditions for stable forming of the Al–Zn–Mg–Cu alloy. Microstructural analysis revealed MgZn2 precipitation induced by hot deformation, with crystallographic defects enhancing nucleation rates and precipitate refinement.

Abstract Methylation-based liquid biopsies show promises in detecting cancer using circulating cell-free DNA; however, current limitations impede clinical application. Most assays necessitate substantial DNA inputs, posing challenges. Additionally, underrepresented tumor DNA fragments may go undetected during exponential amplification steps of traditional sequencing methods. Here, we report linear amplification-based bisulfite sequencing (LABS), enabling linear amplification of bisulfite-treated DNA fragments in a genome-wide, unbiased fashion, detecting cancer abnormalities with sub-nanogram inputs. Applying LABS to 100 patient samples revealed cancer-specific patterns, copy number alterations, and enhanced cancer detection accuracy by identifying tissue-of-origin and immune cell composition.

The role of processing bodies (P-bodies) in tumorigenesis and tumor progression is not well understood. Here, we showed that the oncogenes YAP/TAZ promote P-body formation in a series of cancer cell lines. Mechanistically, both transcriptional activation of the P-body-related genes SAMD4A, AJUBA, and WTIP and transcriptional suppression of the tumor suppressor gene PNRC1 are involved in enhancing the effects of YAP/TAZ on P-body formation in colorectal cancer (CRC) cells. By reexpression of PNRC1 or knockdown of P-body core genes (DDX6, DCP1A, and LSM14A), we determined that disruption of P-bodies attenuates cell proliferation, cell migration, and tumor growth induced by overexpression of YAP5SA in CRC. Analysis of a pancancer CRISPR screen database (DepMap) revealed co-dependencies between YAP/TEAD and the P-body core genes and correlations between the mRNA levels of SAMD4A, AJUBA, WTIP, PNRC1, and YAP target genes. Our study suggests that the P-body is a new downstream effector of YAP/TAZ, which implies that reexpression of PNRC1 or disruption of P-bodies is a potential therapeutic strategy for tumors with active YAP.

Background/Aims: Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is widely accepted as a radical surgery for refractory ulcerative colitis (UC). Definite results on the appropriate pouch length for an evaluation of the risk-to-benefit ratio regarding technical complications and long-term quality of life (QOL) are still scarce. Methods: Data on UC patients who underwent IPAA from 2008 to 2022 in four well-established pouch centers affiliated to China UC Pouch Center Union were collected. Results: A total of 208 patients with a median follow-up time of 6.0 years (interquartile range, 2.3 to 9.0 years) were enrolled. The median lengths of the patients’ short and long pouches were 14.0 cm (interquartile range, 14.0 to 15.0 cm) and 22.0 cm (interquartile range, 20.0 to 24.0 cm), respectively. Patients with a short J pouch configuration were less likely to achieve significantly improved long-term QOL (p=0.015) and were prone to develop late postoperative complications (p=0.042), such as increased defecation frequency (p=0.003) and pouchitis (p=0.035). A short ileal pouch was an independent risk factor for the development of late postoperative complications (odds ratio, 3.100; 95% confidence interval, 1.519 to 6.329; p=0.002) and impaired longterm QOL improvement (odds ratio, 2.221; 95% confidence interval, 1.218 to 4.050, p=0.009). Conclusions: The length of the J pouch was associated with the improvement in long-term QOL and the development of late post-IPAA complications. A long J pouch configuration could be a considerable surgical option for pouch construction.

Abstract The occurrence of systemic inflammatory response after percutaneous transhepatic gallbladder drainage brings great risks to patients and is one of the challenges faced by clinicians. Therefore, it is of great significance to find a suitable prediction method for clinicians to intervene early and reduce the transformation of serious complications. Easy-to-obtain and objectively measured clinical features were screened, and logistic regression was used to construct a prediction model. The predictive ability of the model was evaluated by using the receiver operating characteristic curve and the decision curve in the validation set and the training set, respectively. Nine clinical features (CRP, Fever, DBIL, Obstruction, Bile properties, PCT, Length, Width, and Volume factor) were used to construct the prediction model, and the validation results showed that the prediction model had good performance in the training set (AUC = 0.83) and the validation set (AUC = 0.81). The decision curve also showed that the predictive ability of the model incorporating nine clinical features is better than that of a single clinical feature. The model we constructed can accurately predict the occurrence of SIRS, which can guide clinicians to take treatment measures and avoid the deterioration of complications.

Abstract N 6 -methyladenosine (m6A) maintains maternal RNA stability in oocytes. One regulator of m6A, ALKBH5, reverses m6A deposition and is essential in RNA metabolism. However, the specific role of ALKBH5 in oocyte maturation remains elusive. Here, we show that Alkbh5 depletion causes a wide range of defects in oocyte meiosis and results in female infertility. Temporal profiling of the maternal transcriptomes revealed striking RNA accumulation in Alkbh5 −/− oocytes during meiotic maturation. Analysis of m6A dynamics demonstrated that ALKBH5-mediated m6A demethylation ensures the timely degradation of maternal RNAs, which is severely disrupted following Alkbh5 −/− depletion. A distinct subset of transcripts with persistent m6A peaks are recognized by the m6A reader IGF2BP2 and thus remain stabilized, resulting in impaired RNA clearance. Additionally, reducing IGF2BP2 in Alkbh5-depleted oocytes partially rescued these defects. Overall, this work identifies ALKBH5 as a key determinant of oocyte quality and unveil the facilitating role of ALKBH5-mediated m6A removal in maternal RNA decay.

Accurate estimation of the distribution of POC in the sea surface is an important issue in understanding the carbon cycle at the basin scale in the ocean. This study explores the best machine learning approach to determine the distribution of POC in the ocean surface layer based on data obtained using satellite remote sensing. In order to estimate and verify the accuracy of this method, it is necessary to obtain a large amount of POC data from field observations, so this study was conducted in the Mediterranean Sea, where such data have been obtained and published. The research initially utilizes the Geographic Detector (GD) method to identify spatial correlations between POC and 47 environmental factors in the region. Four machine learning models of a Bayesian optimized random forest (BRF), a backpropagation neural network, adaptive boosting, and extreme gradient boosting were utilized to construct POC assessment models. Model validation yielded that the BRF exhibited superior performance in estimating sea-surface POC. To build a more accurate tuneRanger random forest (TRRF) model, we introduced the tuneRanger R package for further optimization, resulting in an R2 of 0.868, a mean squared error of 1.119 (mg/m3)2, and a mean absolute error of 1.041 mg/m3. It was employed to estimate the surface POC concentrations in the Mediterranean for May and June 2017. Spatial analysis revealed higher concentrations in the west and north and lower concentrations in the east and south, with higher levels near the coast and lower levels far from the coast. Additionally, we deliberated on the impact of human activities on the surface POC in the Mediterranean. This research contributes a high-precision method for satellite retrieval of surface POC concentrations in the Mediterranean, thereby enriching the understanding of POC dynamics in this area.

AIM:To observe the effect of implantable collamer lens V4c(ICL V4c)implantation on high myopia, and the changes in anterior segment morphology.METHODS:A prospective study was conducted on 100 patients(200 eyes)with high myopia who were treated with ICL V4c implantation in the hospital from February 2018 to March 2021. The best corrected visual acuity(BCVA), uncorrected visual acuity(UCVA), intraocular pressure, higher-order aberration, anterior segment morphology [iridocorneal angle(ICA), central anterior chamber depth(ACD), anterior chamber volume(ACV), central corneal thickness(CCT)and K-value(K)], photopic and scotopic contrast sensitivity before operation and 6 and 12mo after operation were comparatively analyzed.RESULTS:All patients were followed-up. UCVA and BCVA were significantly improved at 6 and 12mo after operation(P0.05). Spherical aberration, ICA, ACD and ACV at 6 and 12mo after operation were significantly smaller than those before operation(P0.05).CONCLUSION:Although ICA, ACD and ACV in patients with high myopia are reduced after ICL V4c implantation, the operation can effectively improve visual acuity and visual quality.

Abstract Background Studies have shown that sperm-borne microRNAs (miRNAs) are involved in mammalian preimplantation embryonic development. In humans, spermatozoan miR-34c levels are correlated with in vitro fertilization outcomes, such as embryo quality and the clinical pregnancy and live birth rates. In rabbits and cows, miR-34c improves the developmental competence of embryos generated by somatic cell nuclear transfer. However, the mechanisms underlying the regulation of embryonic development by miR-34c remain unknown. Methods Female C57BL/6 mice (6–8 weeks old) were superovulated, and pronucleated zygotes were collected and microinjected with an miR-34c inhibitor or a negative-control RNA. The embryonic development of the microinjected zygotes was evaluated, and the messenger RNA (mRNA) expression profiles of the embryos at the two-cell, four-cell and blastocyst stages (five embryos per group) were determined by RNA sequencing analysis. Gene expression levels were verified by reverse transcription–quantitative polymerase chain reaction. Cluster analysis and heat map visualization were performed to detect differentially expressed mRNAs. Pathway and process enrichment analyses were performed using ontology resources. Differentially expressed mRNAs were systematically analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins database to determine their biological functions. Results Embryonic developmental potential was significantly reduced in zygotes microinjected with the miR-34c inhibitor compared with those microinjected with a negative-control RNA. Two-cell stage embryos microinjected with an miR-34c inhibitor presented altered transcriptomic profiles, with upregulated expression of maternal miR-34c target mRNAs and classical maternal mRNAs. Differentially expressed transcripts were mainly of genes associated with lipid metabolism and cellular membrane function at the two-cell stage, with cell-cycle phase transition and energy metabolism at the four-cell stage; and with vesicle organization, lipid biosynthetic process and endomembrane system organization at the blastocyst stage. We also showed that genes related to preimplantation embryonic development, including Alkbh4, Sp1, Mapk14, Sin3a, Sdc1 and Laptm4b, were significantly downregulated after microinjection of an miR-34c inhibitor. Conclusions Sperm-borne miR-34c may regulate preimplantation embryonic development by affecting multiple biological processes, such as maternal mRNA degradation, cellular metabolism, cell proliferation and blastocyst implantation. Our data demonstrate the importance of sperm-derived miRNAs in the development of preimplantation embryos.

Particulate organic carbon (POC) is an essential component of the carbon pump within marine organisms. Exploring estimation methods for POC holds substantial significance for understanding the marine carbon cycle. In this study, we investigated the spatial heterogeneity of 30 factors and POC concentrations using geodetector to account for nonlinearity, diversity, and complexity. Ultimately, 20 factors including sea surface temperature, sea surface salinity, and chlorophyll-a were selected as modeling variables. Six machine learning models—backpropagation neural network, convolutional neural network, attention-based neural network, random forest (RF), adaptive boosting, and extreme gradient boosting were used to compare their performance. The results indicate that among the six machine learning algorithms, RF exhibits the strongest performance, with a root mean square error of 0.11 [log(mg/m3)] and an average percentage deviation of 2.73%. Global annual average sea surface POC concentrations were estimated for 2007 and compared to NASA’s POC product. The outcomes indicate that the RF model-based estimation method displays enhanced accuracy in estimating POC concentrations within intricate coastal environments, while the backpropagation neural network performed better in estimating POC concentrations in open ocean areas. Leveraging the RF model, global sea surface POC concentrations were estimated for the years 2007 through 2016, enabling a spatiotemporal analysis. The analysis unveils heightened POC concentrations in coastal regions and lower levels in open ocean areas. Furthermore, POC concentrations were greater in high-latitude regions compared to mid and low latitude counterparts. In conclusion, the global sea surface POC product in this study exhibits heightened spatial resolution and improved data completeness in contrast to other products. It enhances the accuracy of conventional POC estimation methods, particularly within coastal regions.

ABSTRACTBackground: Elucidating epigenetic mechanisms could provide new biomarkers for disease diagnosis and prognosis. Technological advances allow genome-wide profiling of 5-hydroxymethylcytosines (5hmC) in liquid biopsies. 5hmC-Seal followed by NGS is a highly sensitive technique for 5hmC biomarker discovery in cfDNA. Currently, 5hmC Seal is optimized for EDTA blood collection. We asked whether heparin was compatible with 5hmC Seal as many clinical and biobanked samples are stored in heparin.Methods: We obtained 60 samples in EDTA matched to 60 samples in heparin from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Samples were comprised of 30 controls and 30 individuals who were later diagnosed with colon cancer. We profiled genome-wide 5hmC in cfDNA using 5hmC-Seal assay followed by NGS. The 5hmC profiling data from samples collected in EDTA were systematically compared to those in heparin across various genomic features.Results: cfDNA isolation and library construction appeared comparable in heparin vs. EDTA. Typical genomic distribution patterns of 5hmC, including gene bodies and enhancer markers, were comparable in heparin vs. EDTA. 5hmC analysis of cases and controls yielded highly correlated differential features suggesting that both anticoagulants were compatible with 5hmC Seal assay.Conclusions: While not currently recommended for the 5hmC-Seal protocol, blood samples stored in heparin were successfully used to generate analysable and biologically relevant genome-wide 5hmC profiling. Our findings are the first to support opportunities to expand the biospecimen resource to heparin samples for 5hmC Seal and perhaps other PCR-based technologies in epigenetic research.

Abstract Although the MAPK/MEK/ERK pathway is prevalently activated in colorectal cancer (CRC), MEK/ERK inhibitors show limited efficiency in clinic. As a downstream target of MAPK, ELK4 is thought to work primarily by forming a complex with SRF. Whether ELK4 can serve as a potential therapeutic target is unclear and the transcriptional regulatory mechanism has not been systemically analyzed. Here, it is shown that ELK4 promotes CRC tumorigenesis. Integrated genomics‐ and proteomics‐based approaches identified SP1 and SP3, instead of SRF, as cooperative functional partners of ELK4 at genome‐wide level in CRC. Serum‐induced phosphorylation of ELK4 by MAPKs facilitated its interaction with SP1/SP3. The pathological neoangiogenic factor LRG1 is identified as a direct target of the ELK4‐SP1/SP3 complex. Furthermore, targeting the ELK4‐SP1/SP3 complex by combination treatment with MEK/ERK inhibitor and the relatively specific SP1 inhibitor mithramycin A (MMA) elicited a synergistic antitumor effect on CRC. Clinically, ELK4 is a marker of poor prognosis in CRC. A 9‐gene prognostic model based on the ELK4‐SP1/3 complex‐regulated gene set showed robust prognostic accuracy. The results demonstrate that ELK4 cooperates with SP1 and SP3 to transcriptionally regulate LRG1 to promote CRC tumorigenesis in an SRF‐independent manner, identifying the ELK4‐SP1/SP3 complex as a potential target for rational combination therapy.

Rydberg electromagnetically-induced transparency has been widely studied as a medium supporting light propagation under the action of nonlocal nonlinearities. Recently, optical potentials based on moiré lattices (MLs) were introduced for exploring unconventional physical states. Here, we predict a possibility of creating fully three-dimensional (3D) light bullets (LBs) in cold Rydberg gases under the action of ML potentials. The nonlinearity includes local self-defocusing and long-range focusing terms, the latter one induced by the Rydberg-Rydberg interaction. We produce zero-vorticity LB families of the fundamental, dipole, and quadrupole types, as well as vortex LBs. They all are gap solitons populating finite bandgaps of the underlying ML spectrum. Stable subfamilies are identified utilizing the combination of the anti-Vakhitov-Kolokolov criterion, computation of eigenvalues for small perturbations, and direct simulations.

Abstract Background A prognostic assessment method with good sensitivity and specificity plays an important role in the treatment of pancreatic cancer patients. Finding a way to evaluate the prognosis of pancreatic cancer is of great significance for the treatment of pancreatic cancer. Methods In this study, GTEx dataset and TCGA dataset were merged together for differential gene expression analysis. Univariate Cox regression and Lasso regression were used to screen variables in the TCGA dataset. Screening the optimal prognostic assessment model is then performed by gaussian finite mixture model. Receiver operating characteristic (ROC) curves were used as an indicator to assess the predictive ability of the prognostic model, the validation process was performed on the GEO datasets. Results Gaussian finite mixture model was then used to build 5-gene signature (ANKRD22, ARNTL2, DSG3, KRT7, PRSS3). Receiver operating characteristic (ROC) curves suggested the 5-gene signature performed well on both the training and validation datasets. Conclusions This 5-gene signature performed well on both our chosen training dataset and validation dataset and provided a new way to predict the prognosis of pancreatic cancer patients.

Fractional vortex beams have attracted increasing attention due to their complex yet intriguing physical properties, such as radial notch intensity distribution and higher degrees of modulation in orbital angular momentum. In this study, we experimentally investigated and compared the beam spread and beam wander characteristics of fractional-order vortex beams with those of integer-order vortex beams after passing through a turbulent atmosphere simulator with varying turbulence intensities. Our results revealed that the beam spread of both fractional-order and integer-order vortex beams increased in a stepwise manner with the topological charge number, indicating that a larger topological charge number resulted in more severe beam spread. Interestingly, we observed that the beam radius of fractional-order vortex beams between two adjacent integer orders initially grew slowly and then rapidly before finally stabilizing into a curvilinear growth trend. This is in contrast to the linear growth trend exhibited by the beam radius of integer-order vortex beams. Furthermore, we found that the growth of the beam radius of half-integer-order vortex beams followed the linear growth trend of the beam radius of integer-order vortex beams. When the integer part of the topological charge was fixed, we observed that stronger turbulence resulted in more severe beam wander for both integer-order and fractional-order vortex beams, with the variance of the center-of-mass drift following the same growth curve. However, when the turbulence intensity is constant, both integer-order and fractional-order vortex beams exhibit a weaker beam wander effect with increasing topological charge. Our findings may provide valuable insights for applications such as optical communication and optical measurement using fractional-order vortex beams.

Abstract Background DNA N6-methyldeoxyadenosine (6mA) is rarely present in mammalian cells and its nuclear role remains elusive. Results Here we show that hypoxia induces nuclear 6mA modification through a DNA methyltransferase, METTL4, in hypoxia-induced epithelial-mesenchymal transition (EMT) and tumor metastasis. Co-expression of METTL4 and 6mA represents a prognosis marker for upper tract urothelial cancer patients. By RNA sequencing and 6mA chromatin immunoprecipitation-exonuclease digestion followed by sequencing, we identify lncRNA RP11-390F4.3 and one novel HIF-1α co-activator, ZMIZ1, that are co-regulated by hypoxia and METTL4. Other genes involved in hypoxia-mediated phenotypes are also regulated by 6mA modification. Quantitative chromatin isolation by RNA purification assay shows the occupancy of lncRNA RP11-390F4.3 on the promoters of multiple EMT regulators, indicating lncRNA-chromatin interaction. Knockdown of lncRNA RP11-390F4.3 abolishes METTL4-mediated tumor metastasis. We demonstrate that ZMIZ1 is an essential co-activator of HIF-1α. Conclusions We show that hypoxia results in enriched 6mA levels in mammalian tumor cells through METTL4. This METTL4-mediated nuclear 6mA deposition induces tumor metastasis through activating multiple metastasis-inducing genes. METTL4 is characterized as a potential therapeutic target in hypoxic tumors.

Abstract Background A high recurrence rate has always been a serious problem for treatment of hepatocellular carcinoma (HCC). Exploring predictors of postoperative and posttransplantation recurrence in patients with HCC can guide treatment strategies for clinicians. Results In this study, logistic regression and multivariate Cox regression models were constructed with microRNA expression profile data from The Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO). The accuracy of predictions was assessed using receiver operating characteristic curve (ROC) and Kaplan‒Meier survival curve analyses. The results showed that the combination of 10 miRNAs (including hsa-miR-509-3p, hsa-miR-769-3p, hsa-miR-671-3p, hsa-miR-296-5p, hsa-miR-767-5p, hsa-miR-421, hsa-miR-193a-3p, hsa-miR-139-3p, hsa-miR-342-3p, and hsa-miR-193a-5p) accurately predicted postoperative and posttransplantation malignancy recurrence in HCC patients and was also valuable for prognostic evaluation of HCC patients. The 10-miRNA prediction model might assist doctors in making prognoses for HCC patients who have a high probability of relapse following surgery and in offering additional, individualized treatment to lessen that risk.

Abstract Background CONSTANS (CO) and CONSTANS-LIKE (COL) transcription factors have been known to regulate a series of cellular processes including the transition from the vegetative growth to flower development in plants. However, their role in regulating fruit yield in tomato is poorly understood. Result In this study, the tomato ortholog of Arabidopsis CONSTANS, SlCOL1, was shown to play key roles in the control of flower development and fruit yield. Suppression of SlCOL1 expression in tomato was found to lead to promotion of flower and fruit development, resulting in increased tomato fruit yield. On the contrary, overexpression of SlCOL1 disturbed flower and fruit development, and significantly reduced tomato fruit yield. Genetic and biochemical evidence indicated that SlCOL1 controls inflorescence development by directly binding to the promoter region of tomato inflorescence-associated gene SINGLE-FLOWER TRUSS (SFT) and negatively regulating its expression. Additionally, we found that SlCOL1 can also negatively regulate fruit size in tomato. Conclusions Tomato SlCOL1 binds to the promoter of the SFT gene, down-regulates its expression, and plays a key role in reducing the fruit size.

AIM: To compare the differences in choroidal structure between hyperopic amblyopia and normal children of the same age by the enhanced depth imaging optical coherence tomography(EDI-OCT)technique.METHODS: There were 35 cases in 50 eyes of children with hyperopic amblyopia visiting our hospital in January 2021 to December 2021 selected in the amblyopic group, and 30 cases in 51 eyes of healthy children who matched general data in the same period were selected in the control group. EDI-OCT examination was performed to measure the choroidal thickness(CT). After image processing, the total choroidal area(TCA), luminal area(LA), stromal area(SA)and choroidal vascularity index(CVI)were obtained.RESULTS: TCA(except inferior quadrant), SA(except inferior quadrant of the outer ring), LA and CT(except inferior and temporal quadrant )in the amblyopic group of each area were significantly larger than that in the control group(P0.05). There was no significant difference in CT for all degrees of hyperopic amblyopia, with the exception of the nasal quadrant(P>0.05).CONCLUSION: Hyperopic amblyopia is accompanied with abnormal choroidal structure. As the degree of hyperopia increases, TCA, LA and SA exhibit increasing trends. The changes in choroidal structure are presumed to be related to hyperopic amblyopia.

Hippo signalling is often deregulated in cancers. Here the authors show that CK2 enhances the cooperation of HHEX with YAP-TEAD complex to promote colorectal tumorigenesis.

Summary: Ruptured ectopic pregnancy (REP), a pregnancy complication caused by aberrant implantation, deep invasion, and overgrowth of embryos in fallopian tubes, could lead to rupture of fallopian tubes and accounts for 4%–10% of pregnancy-related deaths. The lack of ectopic pregnancy phenotypes in rodents hampers our understanding of its pathological mechanisms. Here, we employed cell culture and organoid models to investigate the crosstalk between human trophoblast development and intravillous vascularization in the REP condition. Compared with abortive ectopic pregnancy (AEP), the size of REP placental villi and the depth of trophoblast invasion are correlated with the extent of intravillous vascularization. We identified a key pro-angiogenic factor secreted by trophoblasts, WNT2B, that promotes villous vasculogenesis, angiogenesis, and vascular network expansion in the REP condition. Our results reveal the important role of WNT-mediated angiogenesis and an organoid co-culture model for investigating intricate communications between trophoblasts and endothelial/endothelial progenitor cells.

Polybutylene succinate (PBS) and a series of multi-block hydroxyl-terminated diol copolymers were synthesized by a "one-step"method with succinic anhydride (SAA) and 1,4-butanediol (BDO) as monomers, and terminal hydroxy diols as copolymer monomer. The condensation product of phenolphthalein and SAA was used to participate in the copolymerization of SAA and BDO, and biodegradable triblock polyester thermoplastic elastomers with rigid and flexible chain segments, poly(butylene succinate-co-phenolphthalein butylene succinate) (SAA-PHE-PBS), were prepared by the chain modulation synthesis method. The molecular weight, chemical structure composition, thermal properties and crystallization property of PBS and its copolymers were investigated, and their biodegradability was tested with Candida antarctica lipase B. The results showed that the glass transition temperature of multi-block hydroxyl-terminated diol copolymer did not change much, the melting tempe-rature did not change significantly, the crystallinity decreased, the hydrophilicity was improved, and the biodegradability was greatly improved. The glass transition temperature of the triblock thermoplastic elastomer SAA-PHE-PBS was elevated, the crystallinity was not much different from that of PBS, the hydrophobicity was stronger than that of PBS, resi-dual mass fraction of SAA-PHE-PBS increased, and the biodegradability showed different degrees of decline.

Abstract The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls.

Motion artifacts deteriorate the quality of magnetic resonance (MR) images. This study proposes a new method to detect phase-encoding (PE) lines corrupted by motion and remove motion artifacts in MR images. 67 cases containing 8710 slices of axial T2-weighted images from the IXI public dataset were split into three datasets, i.e., training (50 cases/6500 slices), validation (5/650), and test (12/1560) sets. First, motion-corrupted k-spaces and images were simulated using a pseudo-random sampling order and random motion tracks. A convolutional neural network (CNN) model was trained to filter the motion-corrupted images. Then, the k-space of the filtered image was compared with the motion-corrupted k-space line-by-line, to detect the PE lines affected by motion. Finally, the unaffected PE lines were used to reconstruct the final image using compressed sensing (CS). For the simulated images with 35%, 40%, 45%, and 50% unaffected PE lines, the mean peak signal-to-noise ratio (PSNRs) of resulting images (mean±standard deviation) were 36.129±3.678, 38.646±3.526, 40.426±3.223, and 41.510±3.167, respectively, and the mean structural similarity (SSIMs) were 0.950±0.046, 0.964±0.035, 0.975±0.025, and 0.979±0.023, respectively. For images with more than 35% PE lines unaffected by motion, images reconstructed with proposed algorithm exhibited better quality than those images reconstructed with CS using 35% under-sampled data (PSNR 37.678±3.261, SSIM 0.964±0.028). It was proved that deep learning and k-space analysis can detect the k-space PE lines affected by motion and CS can be used to reconstruct images from unaffected data, effectively alleviating the motion artifacts.

A light source with extended spectral bandwidth applied in optical coherence tomography (OCT) systems produces highly accurate micro-scale imaging structures owing to the attainable high-axial resolution. This study presents a wide tuning range of a wavelength-swept laser to improve the axial resolution. Linear cavity configuration was performed for bidirectional photonic resonance using two semiconductor optical amplifiers placed parallelly. A polygon scanner-based tunable filter produced a broad scanning range of 155 nm from 917 nm to 1072 nm and an axial resolution of 3.4 μm in air. Bench-top imaging of a phantom made of food wraps was performed with 22.6 μm transverse resolution to evaluate the performance of the swept laser for high-resolution OCT.

Unexplained recurrent spontaneous abortion (URSA) is one of the most intractable clinical challenges in reproduction. As a specific type of endogenous non-coding RNA, circular RNAs (circRNAs) have great pre-clinical diagnostic and therapeutic values in diseases. Recently, thousands of circRNAs were detected in human pre-implantation embryos, indicating that circRNAs potentially have important regulatory functions. However, the roles of circRNAs in URSA remain largely unknown. In this study, we elucidated deregulated circRNA expression and distinct competing endogenous RNA (ceRNA) networks by comparing URSA placental villus with that of patients with normal pregnancy using microarrays. We characterized a distinct circRNA, circRNA-0050703, which is downregulated in URSA placental villus (thus we named it circRNA-DURSA). Silencing of circRNA-DURSA results in trophoblast cell apoptosis in vitro. Furthermore, mechanistic dissection revealed that circRNA-DURSA exerts its effects by competitively binding to miR-760, which post-transcriptionally targets HIST1H2BE. Additionally, after circRNA-DURSA silencing in vivo, the numbers of implanted embryos decreased significantly. These results reveal the regulatory roles of circRNA-DURSA in trophoblasts and identified a distinct circRNA-DURSA/miR-760/HIST1H2BE axis as potentially important diagnostic and therapeutic targets for URSA treatment.

Plum (Prunus salicina Lindl.) is one of the most widely cultivated and important fruit trees in temperate and cold regions. Fruit color is a significant trait relating to fruit quality in plum. However, its development mechanism has not been studied from the aspects of transcriptional regulation and metabolomic progress. To reveal the mechanism of fruit color developments in plums, we selected the fruits of two plum cultivars, ‘Changli84’ (Ch84, red fruit) and ‘Dahuangganhe’ (D, yellow fruit) as plant materials for transcriptome sequencing and metabolomic analysis were performed. Based on the data of transcriptome and metabolome at three fruit developmental stages, young fruit stage, color-change stage, and maturation stage, we identified 2,492 differentially expressed genes (DEGs) and 54 differential metabolites (DMs). The KEGG analysis indicated that “Flavonoid biosynthesis” was significantly enriched during three fruit development stages. Some DEGs in the “Flavonoid biosynthesis” pathway, had opposite trends between Ch84 and D, including chalcone synthase (CHS), dihydroflavonol 4-reductase (DFR) and flavonol synthase (FLS). Also, the genes encoding MYB–bHLH–WD (MBW) protein complexes, especially MYBs and bHLHs, showed a close relationship with plum fruit color. In the current study, DMs like procyanidin B1, cyanidin 3-glucoside, and cyanidin-3-O-alpha-arabinopyranoside were key pigments (or precursors), while the carotene and carotenoids did not show key relationships with fruit color. In conclusion, the anthocyanins dominate the color change of plum fruit. Carotenes and carotenoids might be related to the color of plum fruit, but do not play a dominate role.

Abstract Anthocyanins are the largest group of water-soluble pigments and beneficial for human health. Although most plants roots have the potential to express natural biosynthesis pathways required to produce specialized metabolites such as anthocyanins, the anthocyanin synthesis is specifically silenced in roots. To explore the molecular mechanism of absence and production ability of anthocyanin in the roots, investigated the effect of a bHLH gene AmDelila, and an R2R3-MYB gene AmRosea1, which are the master regulators of anthocyanin biosynthesis in Antirrhinum majus flowers, by expressing these genes in transformed hairy roots of A. majus. Co-ectopic expression of both AmDelila and AmRosea1 significantly upregulated the expression of the key target structural genes in the anthocyanin biosynthesis pathway. Furthermore, this resulted in strongly enhanced anthocyanin accumulation in transformed hairy roots. Ectopic expression of AmDelila alone did not gives rise to any significant anthocyanin accumulation, however, ectopic expression of AmRosea1 alone clearly upregulated expression of the main structural genes as well as greatly promoted anthocyanin accumulation in transformed hairy roots, where the contents reached 0.773–2.064 mg/g fresh weight. These results suggest that AmRosea1 plays a key role in the regulatory network in controlling the initiation of anthocyanin biosynthesis in roots, and the combination of AmRosea1 and hairy root culture is a powerful tool to study and production of anthocyanins in the roots of A. majus.

BackgroundThe simple endoscopic score for Crohn's disease (SES-CD) is a widely used index to evaluate clinical and endoscopic activity. However, the association and predictive value of SES-CD for intestinal obstruction in Crohn's disease (CD) remains unclear. We aimed to establish the best cut-off indicators of SES-CD for early clinical intervention and subsequent prevention of intestinal obstruction in CD.MethodsData on patients with CD evaluated at our institute from January 2016 to January 2022 were retrospectively collected. The SES-CD and Crohn's Disease Activity Index scores used in the analysis indicated the results of the first clinical and colonoscopy evaluations after hospitalization. The primary outcome was the occurrence of intestinal obstruction during admission and follow-up.ResultsA total of 248 patients with a median follow-up time of 2 years [interquartile range: 1.0–4.0] were enrolled, of which 28.2% developed intestinal obstruction. An SES-CD score of 8 was the most significant threshold evaluation, and SES-CD ≥8 had the largest area under the receiver operating characteristic curve (0.705), with a sensitivity of 52.9% and specificity of 88.2% in predicting intestinal obstruction. Furthermore, SES-CD ≥8 had the greatest risk factor for intestinal obstruction (odds ratio: 7.731; 95% confidence interval: 3.901–15.322; p

Abstract Background This study examines the socioeconomic differentials in trends in the prevalence of hypertension and pre-hypertension and hypertension awareness, treatment, and control in rural Southwestern China. Methods Two cross-sectional interviews and health examination surveys were administered in rural Yunnan Province, including 6,350 consenting participants in 2009 and 6,359 consenting participants in 2016 (aged ≥ 35 years). Participant demographics, socioeconomic status (SES), and ethnicity, along with information about hypertension awareness, treatment, and control, were collected using similar questionnaires in the two surveys. The participants’ blood pressure levels were also measured. Results From 2009 to 2016, the prevalence of hypertension substantially increased from 28.4% to 39.5% (P

Abstract Background This study examines the association between socioeconomic and lifestyle factors and the prevalence of hypertension among elderly individuals in rural Southwest China. Methods A cross-sectional survey of 4833 consenting adults aged ≥ 60 years in rural regions of Yunnan Province, China, was conducted in 2017. Data on individual socioeconomic status, sleep quality, physical activity level, and family history of hypertension were collected with a standardized questionnaire. Blood pressure, fasting blood glucose, height, weight, and waist circumference were also measured. An individual socioeconomic position (SEP) index was constructed using principal component analysis. Structural equation modelling (SEM) was applied to analyse the association between socioeconomic and lifestyle factors and the prevalence of hypertension. Results The overall prevalence of hypertension was 50.6% in the study population. Body fat distribution, including measures of obesity and central obesity, had the greatest total effect on hypertension (0.21), followed by family history of hypertension (0.14), biological sex (0.08), sleep quality (− 0.07), SEP (− 0.06), physical inactivity (0.06), and diabetes (0.06). Body fat distribution, SEP, and family history of hypertension had both direct and indirect effects on hypertension, whereas physical inactivity, diabetes, and sleep quality were directly associated with the prevalence of hypertension. Biological sex was indirectly associated with the prevalence of hypertension. Conclusions SEP, body fat distribution, physical inactivity, diabetes, and sleep quality critically influence the prevalence of hypertension. Future interventions to prevent and control hypertension should give increased attention to individuals with low SEP and should focus on controlling diabetes and obesity, increasing physical activity levels, and improving quality of sleep among older adults aged ≥ 60 years in rural Southwest China.

Background We aimed to analyze the success rates and the access patency rates at 12 months between patients on chronic hemodialysis with symptomatic central venous stenosis (CVS) or occlusion (CVO), receiving high or low balloon inflation pressure for treatment. Methods We performed a retrospective study in which angioplasty balloons were inflated using a low-pressure or a high-pressure for the management of hemodialysis patients with CVS/CVO. The outcomes of this study were the success rate and the access patency rates at 12 months after balloon angioplasty, and the differences between groups were compared. Results We included a total of 74 patients on hemodialysis and assigned them to the low-pressure or the high-pressure groups. Success rates in patients of the high-pressure group (94.12%) were higher than those in patients of the low-pressure group (67.50%) (p = 0.005). With a total of 59 patients with technical success, at 6 and 12 months after angioplasty, the rates of access patency in the low-pressure group were 68 and 48%, respectively; on the other hand, the primary patency rates in the high-pressure group were 86.67% (6-months) and 76.67% (12-months). The 6 and 12 months post-interventional patency rates were higher in patients of the high-pressure group than those in patients of the low-pressure group (p = 0.10 at 6 months and p = 0.03 at 12 months). Conclusions Compared to balloon angioplasty using a low inflation pressure, hemodialysis patients with CVS/CVO receiving angioplasty using a high inflation pressure have significantly higher technical success and 12-month patency rates.

Betaine is a new surfactant with good application prospects in high-temperature and high-salinity reservoirs. The interfacial properties of two kinds of betaine mixtures with a good synergistic effect were evaluated in this paper. On this basis, the effects of temperature-resistant, salt-resistant polymers with different contents of 2-acrylamide-2-methylpropanesulfonic acid (AMPS) on dynamic interfacial tensions (IFTs) against n-alkanes and crude oil were studied. The experimental results show that the IFTs between betaine ASB and n-alkanes can be reduced to ultra-low values by compounding with anionic surfactant petroleum sulfonate (PS) and extended anionic surfactant alkoxyethylene carboxylate (AEC), respectively. ASB@AEC is very oil-soluble with nmin value ≥14, and ASB@PS is relatively water-soluble with nmin value of 10. The water solubility of both ASB@PS and ASB@AEC is enhanced by the addition of water-soluble polymers. The HLB of the ASB@AEC solution becomes better against crude oil after the addition of polymers, and the IFT decreases to an ultra-low value as a result. On the contrary, the antagonistic effect in reducing the IFT can be observed for ASB@PS in the same case. In a word, polymers affect the IFTs of surfactant solutions by regulating the HLB.

Freeze–thaw damage is one of the primary causes deteriorating the seismic resistance of reinforced concrete (RC) structures. This paper proposed a freeze–thaw damage deterioration model for C30 concrete, and it can be employed to study the time-varying seismic performance of aging RC columns. Next, this study developed a seismic fragility analysis framework for deteriorating RC columns considering the effect of freeze–thaw damage. Considering the geometric parameters of the case-study bridge, the deterioration characteristics of material, and the uncertainties involved in structural modeling and ground motions, a probabilistic seismic fragility analysis on aging RC columns was conducted. The results indicate that the influence of freeze–thaw damage cannot be ignored in studying the seismic performance of aging RC structures. The seismic fragilities of deteriorating RC columns shown a nonlinear increase trend as the increased of freeze–thaw cycles and severity of the damage state. In the early stage of freeze–thaw cycles, the seismic fragilities of RC columns increased slowly. However, the closer to the later stage of freeze–thaw cycles, the more significant of the increase in the seismic fragilities of the columns.