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Abstract The Challenger Deep (CD) is the deepest known hadal trench in the world. Due to challenges in data sampling at extreme ocean depths, the Lower Circumpolar Deep Water (LCDW) transport and ocean circulation structure in the CD remain unclear. By analyzing data from an extra-deep current meter mooring array, here we find a three-layer circulation in the CD, transitioning downward from westward LCDW flow (about −1.866 ± 2.953 Sv, 1 Sv = 106 m3/s) to cyclonic circulation, and then to anticyclonic circulation. The westward flow reverses its direction during summer, giving evidence for bidirectional connectivity of deep-sea basins, while the cyclonic-anticyclonic circulation is relatively steady. The LCDW intrusion, local topography and turbulent mixing are crucial for modulating the three-layer circulation. Turbulent mixing plays a key role in driving the anticyclonic circulation. Our findings provide insights for understanding the hydrodynamic environment in the ocean’s deepest areas.

Abstract Background The liver effects of concentrated vs. more evenly distributed moderate-to-vigorous physical activity (MVPA) patterns remain unclear. We aimed to examine the association of accelerometer-measured MVPA and different MVPA patterns with liver outcomes. Methods Eighty-eight thousand six hundred fifty-six participants without prior liver diseases from UK Biobank were included. MVPA was measured by a wrist-worn accelerometer. Based on the guideline-based threshold (≥ 150 min/week), MVPA patterns were defined as inactive (

BackgroundEndovascular recanalization is a feasible option for treating symptomatic non-acute middle cerebral artery occlusion (MCAO) patients. Hence, we aimed to establish a new angiographic scoring to grade the recanalization difficulty of MCAO to determine the suitable patients for endovascular treatment.MethodsWe retrospectively analyzed a total of 113 consecutive recurrent symptomatic non-acute MCAO patients who underwent endovascular recanalization from July 2015 to August 2021 in four Chinese comprehensive stroke centers. All patients were reappraised using a new angiographic scoring based on the stump morphology, the MCA occlusion length, MCA bend, and the distal vascular bed of MCAO. We used the final results to establish the patients’ outcomes.ResultsThe total successful recanalization and perioperative complication rates were 83.2% (94/113) and 15.9% (18/113), respectively. No deaths occurred within 30 days. Moreover, 96.9, 90, 87.5, 52.6, and 50% of the patients achieved recanalization with scores of 0, 1, 2, 3, and 4 (p

Background: Bone-destructive diseases including rheumatoid arthritis (RA), osteoporosis, and bone metastases, are increasingly prevalent and worrisome due to the over-activated of osteoclasts. Chongrenside D (CGD) is a furostanol saponin extracted from Smilax china L, which has been demonstrated to have anti-inflammatory properties in our previous research. However, its effect on rheumatoid arthritis, especially on osteoclast differentiation and bone destruction has not yet been investigated. Methods: We evaluated the toxicity of CGD on the cell we used, RANKL-induced osteoclast formation, bone resorption activity, and osteoclast-specific genes or protein expression using bone marrow-derived monocytes (BMMs) -derived osteoclasts. Furthermore, the protective function of CGD on the paws of osteolytic mice was carried out using micro-CT, H&E, TRAP staining, as well as real-time PCR, and western blotting. Inflammatory cytokine levels were conducted through ELISA assay. The relative signaling pathways were investigated using western blotting, immunofluorescence microscopy and real-time PCR. Results: CGD notably inhibited RANKL-induced osteoclast formation, and suppressed the expression of osteoclast markers and actin ring formation, thus attenuating its bone resorption activity. For in vivo work, CGD protected against joint bone destruction induced by LPS, increased trabecular number and thickness, and reduced trabecular separation. CGD also inhibited the levels of inflammatory cytokines IL-6and TNF-α, improved the integrity of joint bones and decreased TRAP-positive staining area. The mechanistic study indicated that CGD down-regulated MMP9 and FAK-Src signaling, which were crucial for the resorption function of osteoclasts. CGD also inhibited MAPK pathway-mediated cell differentiation and survival, finally resulting in weak osteoclastogenesis. Conclusion: CGD exerts a significant anti-osteolytic activity both in vitro and in vivo by inhibiting RANKL-induced osteoclastogenesis and function. Consequently, our study indicated that CGD may have a potential therapeutic role in the precaution of osteolytic bone disease.

Abstract Tropical Cyclones (TCs) are devastating natural disasters. Analyzing four decades of global TC data, here we find that among all global TC-active basins, the South China Sea (SCS) stands out as particularly difficult ocean for TCs to intensify, despite favorable atmosphere and ocean conditions. Over the SCS, TC intensification rate and its probability for a rapid intensification (intensification by ≥ 15.4 m s−1 day−1) are only 1/2 and 1/3, respectively, of those for the rest of the world ocean. Originating from complex interplays between astronomic tides and the SCS topography, gigantic ocean internal tides interact with TC-generated oceanic near-inertial waves and induce a strong ocean cooling effect, suppressing the TC intensification. Inclusion of this interaction between internal tides and TC in operational weather prediction systems is expected to improve forecast of TC intensity in the SCS and in other regions where strong internal tides are present.

Abstract. Background:. Whether functional gastrointestinal disorders (FGIDs) are associated with the long-term risk of chronic kidney disease (CKD) remains unclear. We aimed to investigate the prospective association of FGIDs with CKD and examine whether mental health mediated the association. Methods:. About 416,258 participants without a prior CKD diagnosis enrolled in the UK Biobank between 2006 and 2010 were included. Participants with FGIDs (including irritable bowel syndrome [IBS], dyspepsia, and other functional intestinal disorders [FIDs; mainly composed of constipation]) were the exposure group, and non-FGID participants were the non-exposure group. The primary outcome was incident CKD, ascertained from hospital admission and death registry records. A Cox proportional hazard regression model was used to investigate the association between FGIDs and CKD, and the mediation analysis was performed to investigate the mediation proportions of mental health. Results:. At baseline, 33,156 (8.0%) participants were diagnosed with FGIDs, including 21,060 (5.1%), 8262 (2.0%), and 6437 (1.6%) cases of IBS, dyspepsia, and other FIDs, respectively. During a mean follow-up period of 12.1 years, 11,001 (2.6%) participants developed CKD. FGIDs were significantly associated with a higher risk of incident CKD compared to the absence of FGIDs (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.28–1.44). Similar results were observed for IBS (HR, 1.27; 95% CI, 1.17–1.38), dyspepsia (HR, 1.30; 95% CI, 1.17–1.44), and other FIDs (HR, 1.60; 95% CI, 1.43–1.79). Mediation analyses suggested that the mental health score significantly mediated 9.05% of the association of FGIDs with incident CKD and 5.63–13.97% of the associations of FGID subtypes with CKD. Specifically, the positive associations of FGIDs and FGID subtypes with CKD were more pronounced in participants with a high genetic risk of CKD. Conclusion:. Participants with FGIDs had a higher risk of incident CKD, which was partly explained by mental health scores and was more pronounced in those with high genetic susceptibility to CKD.

Study Region: Min River Basin on the eastern Qinghai-Tibet Plateau. Study Focus: Precipitation is critical for hydrological processes, making accurate data essential for water management and flood forecasting. Satellite precipitation products offer valuable high-resolution spatiotemporal information, with the GSMaP series being widely used. However, comprehensive evaluations of different versions are limited. This study assesses the accuracy of Gauge and MVK products (versions 06, 07, and 08) across spatial and temporal scales and evaluates their performance in detecting precipitation events of varying intensities. New Hydrological Insights for the Study Region: (1) GSMaP versions 06 and 07 exhibit higher detection rates for precipitation events, with POD values exceeding 0.8, while version 08 has a lower false alarm rate, with FAR values below 0.15. (2) GSMaP products are more successful in capturing precipitation events during the rainy season than the dry season. (3) With increasing elevation, the Gauge product consistently maintains a high hit rate and reduced false alarm rate, whereas the MVK product's hit rates improve. (4) For different rainfall intensities, GSMaP products more accurately detect moderate and heavy rain events, with the Gauge product outperforming the MVK product in terms of accuracy. These insights enhance the understanding of GSMaP product performance on eastern edge of the Qinghai-Tibet Plateau, aiding in improved water management practices.

Bacterial exonuclease III (ExoIII), widely acknowledged for specifically targeting double-stranded DNA (dsDNA), has been documented as a DNA repair-associated nuclease with apurinic/apyrimidinic (AP)-endonuclease and 3′→5′ exonuclease activities. Due to these enzymatic properties, ExoIII has been broadly applied in molecular biosensors. Here, we demonstrate that ExoIII (Escherichia coli) possesses highly active enzymatic activities on ssDNA. By using a range of ssDNA fluorescence-quenching reporters and fluorophore-labeled probes coupled with mass spectrometry analysis, we found ExoIII cleaved the ssDNA at 5′-bond of phosphodiester from 3′ to 5′ end by both exonuclease and endonuclease activities. Additional point mutation analysis identified the critical residues for the ssDNase action of ExoIII and suggested the activity shared the same active center with the dsDNA-targeted activities of ExoIII. Notably, ExoIII could also digest the dsDNA structures containing 3′-end ssDNA. Considering most ExoIII-assisted molecular biosensors require the involvement of single-stranded DNA (ssDNA) or nucleic acid aptamer containing ssDNA, the activity will lead to low efficiency or false positive outcome. Our study revealed the multi-enzymatic activity and the underlying molecular mechanism of ExoIII on ssDNA, illuminating novel insights for understanding its biological roles in DNA repair and the rational design of ExoIII-ssDNA involved diagnostics.

Abstract Background We aimed to quantify the association of handgrip strength and self‐reported walking pace with incident Parkinson's disease (PD) in the general population. Methods A total of 419 572 participants (54.1% females, mean age: 56.1 years [SD, 8.2]) without prior PD were included from UK Biobank. Handgrip strength was assessed by dynamometer. Walking pace was self‐reported as slow, average or brisk. The study outcome was incident PD, determined by self‐report data, hospital admission records or death records. Results The mean handgrip strength was 23.5 (SD, 6.3) and 39.6 (SD, 8.9) kg for females and males, respectively. A total of 33 645 (8.0%), 221 682 (52.8%) and 164 245 (39.2%) participants reported slow, average and brisk walking pace, respectively. Over a median follow‐up duration of 12.5 years, 2152 participants developed incident PD. When handgrip strength was assessed as sex‐specific tertiles, compared with those in the third tertile, the adjusted hazard ratios (HRs) (95% confidence interval [CI]) of incident PD for participants in the second and first tertiles were 1.23 (1.09–1.39) and 1.60 (1.42–1.79), respectively. Compared with brisk walking pace, average (HR, 1.33; 95% CI: 1.20–1.47) or slow (HR, 1.84; 95% CI: 1.57–2.15) walking pace was associated with a higher risk of incident PD. A lower grip strength (Tertiles 1 and 2) and an average/slow walking pace accounted for 23.8% and 19.9% of PD cases, respectively. When handgrip strength and walking pace were considered together, the highest risk of incident PD was observed in participants with both lowest handgrip strength and slow walking pace (HR, 2.89; 95% CI: 2.30–3.64). Genetic risks of PD did not significantly modify the relation of handgrip strength (P for interaction = 0.371) or walking pace (P for interaction = 0.082) with new‐onset PD. Conclusions Low handgrip strength and slow walking pace were significantly associated with a higher risk of incident PD, regardless of the individuals' genetic risk profile.

Accurate segmentation of pituitary adenoma lesions is essential for effective diagnosis and treatment planning. However, traditional algorithms struggle with this task due to the variability in lesion shape, position, and the presence of extensive background areas. In response to the above challenges, we develop a segmentation framework for pituitary adenoma that integrates multi-scale residual, channel attention and spatial attention mechanisms. In the encoding stage of MSR-Net, a multi-scale residual block is introduced to enhance the ability of channel information extraction across varying scales. In the decoding phase, we construct two paths: the introduction of channel attention allows for obtaining the nuanced weighting of the response degree of each channel to key information, and the spatial attention is utilized to extract the global dependence of features to ease the interference of complex background on segmentation performance. When tested on the constructed original pituitary adenoma database, the specificity, IoU, Mcc, and Dice of MSR-Net reached 99.74%, 80.87%, 89.12%, and 89.34%, which were 0.16%, 5.96%, 3.76%, and 3.76% higher than traditional U-Net. Furthermore, we embarked extensive ablative studies on the original dataset to dissect and evaluate the efficacy of each key modules integrated into our architectural framework. Finally, we expanded upon the original dataset to create an enhanced database, and the objective evaluation index further verifies the superiority and advanced nature of MSR-Net. Compared with other most advanced segmentation approaches, MSR-Net shows superior segmentation effect and robustness, as well as great potential in clinical application, which provides an important reference for the future research and development of medical image segmentation.

An accurate model is needed to simulate the electromagnetic fields induced by short-period ocean waves to study the influence of the induced fields on the data set of marine magnetotelluric (mMT), marine controlled source electromagnetic (mCSEM), and marine airborne (low altitude) magnetic anomaly detection (MAD). By using a three-dimensional (3-D) linear wave model and directly solving linear equations derived from Maxwell’s equations and boundary conditions of a horizontal layered seabed, we obtained analytical solutions of the six components of the electromagnetic fields induced by three components of the velocity of ocean waves and three components of geomagnetic fields. In addition to horizontal currents induced by the horizontal velocity and vertical geomagnetic field, the contributions from the horizontal current induced by the vertical velocity and horizontal geomagnetic field and vertical current were considered in the governing equations. On the basis of the solutions, we studied how the geomagnetic field and wind fields affect the relationship between the two horizontal components and between the horizontal and vertical components of the electromagnetic fields at the sea surface. We simulated the influence of water depth and wind fields on the distribution of the spectrum and time series of the induced fields by using a typical wave spectrum and directional spectrum. Finally, the possibility of detecting seafloor conductivity structures by using the electromagnetic response of short ocean waves was also discussed.

Abstract Chimeric antigen receptor (CAR)-T therapy requires autologous T lymphocytes from cancer patients, a process that is both costly and complex. Universal CAR-T cell treatment from allogeneic sources can overcome this limitation but is impeded by graft-versus-host disease (GvHD) and host versus-graft rejection (HvGR). Here, we introduce a mutated calcineurin subunit A (CNA) and a CD19-specific CAR into the T cell receptor α constant (TRAC) locus to generate cells that are resistant to the widely used immunosuppressant, cyclosporine A (CsA). These immunosuppressant-resistant universal (IRU) CAR-T cells display improved effector function in vitro and anti-tumour efficacy in a leukemia xenograft mouse model in the presence of CsA, compared with CAR-T cells carrying wild-type CNA. Moreover, IRU CAR-T cells retain effector function in vitro and in vivo in the presence of both allogeneic T cells and CsA. Lastly, CsA withdrawal restores HvGR, acting as a safety switch that can eliminate IRU CAR-T cells. These findings demonstrate the efficacy of CsA-resistant CAR-T cells as a universal, ‘off-the-shelf’ treatment option.

Abstract Objective To analyze the oxidative stress status and its association with tissue neutrophilia and oral steroid response in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. Methods The levels of total oxidant status (TOS) were detected in the sinonasal tissues by using specific assay kits. Tissue neutrophil was examined by immunohistochemical staining, and oxidant status index (OSI) was evaluated in polyps tissues, and the messenger RNA (mRNA) levels of superoxide dismutase 2 (SOD2), aldehyde dehydrogenase 1 (ALDH1A1), and microsomal glutathione S‐transferase 1 (MGST1) were examined using quantitative real‐time polymerase chain reaction in the sinonasal tissues. The receiver operating characteristics (ROCs) curve of ALDH1A1, MGST1, and SOD2 mRNA levels were evaluated to determine the steroid response of CRSwNP patients. Results The levels of TOS and OSI were significantly higher in CRSwNP and CRSsNP than in normal controls, and OSI in polyps tissues was positively associated with tissue neutrophilia and poor steroid response. The ALDH1A1, MGST1, and SOD2 mRNA levels showed comparable accuracy as predictors of poor steroid response indicated by the area under the curve. Conclusion These findings provided evidence that the increased level of oxidative stress contributes to enhanced tissue neutrophilia and poor steroid response in CRSwNP patients.

Abstract The genome of an organism is inherited from its ancestor and continues to evolve over time, however, the extent to which the current version could be altered remains unknown. To probe the genome plasticity of Saccharomyces cerevisiae, here we replace the native left arm of chromosome XII (chrXIIL) with a linear artificial chromosome harboring small sets of reconstructed genes. We find that as few as 12 genes are sufficient for cell viability, whereas 25 genes are required to recover the partial fitness defects observed in the 12-gene strain. Next, we demonstrate that these genes can be reconstructed individually using synthetic regulatory sequences and recoded open-reading frames with a “one-amino-acid-one-codon” strategy to remain functional. Finally, a synthetic neochromsome with the reconstructed genes is assembled which could substitute chrXIIL for viability. Together, our work not only highlights the high plasticity of yeast genome, but also illustrates the possibility of making functional eukaryotic chromosomes from entirely artificial sequences.

Abstract Evidence regarding the association between physical activity and Parkinson’s disease (PD) risk is generally limited due to the use of self-report questionnaires. We aimed to quantify the separate and combined effects of accelerometer-measured light physical activity (LPA), moderate-to-vigorous physical activity (MVPA), sedentary time and exercise timing with incident PD. 96,422 participants without prior PD and with usable accelerometer data were included from UK Biobank. Time spent in sedentary activity, LPA, MVPA, and exercise timing were estimated using machine learning models. The study outcome was incident PD. Over a median follow-up duration of 6.8 years, 313 participants developed PD. There was a L-shaped association for LPA and MVPA, and a reversed L-shaped association for sedentary time, with the risk of incident PD (all P for nonlinearity

Abstract Background The relationship of glucosamine use with incident dementia in the older population remains uncertain. We aimed to evaluate the longitudinal association between habitual glucosamine supplement and the risk of cause-specific dementia and examine the possible effect modifiers on this association. Methods The study included 214,945 participants over the age of 60 who had available information on glucosamine use and did not have dementia at baseline in the UK Biobank. The APOE genotypes were determined by a combination variant of rs429358 and rs7412. The primary outcome was incident vascular dementia, incident Alzheimer’s disease, and incident frontotemporal dementia, respectively. Results Over a median follow-up duration of 12 years, 1039, 1774, and 122 participants developed vascular dementia, Alzheimer’s disease, and frontotemporal dementia, respectively. Overall, habitual glucosamine use was significantly associated with a lower risk of incident vascular dementia (adjusted HR, 0.82; 95%CI, 0.70–0.96), but not significantly associated with incident Alzheimer’s disease (adjusted HR, 1.02; 95%CI, 0.92–1.14) and incident frontotemporal dementia (adjusted HR, 0.95; 95%CI, 0.63–1.43). Moreover, the inverse association between habitual glucosamine use and incident vascular dementia was more pronounced in participants with concomitant supplement of calcium (P-interaction = 0.011), and those without concomitant supplement of zinc (P-interaction = 0.018). However, APOE ε4 dosage and baseline cognitive function did not significantly modify the relationships of glucosamine use with incident vascular dementia or Alzheimer’s disease (All P-interactions > 0.05). Conclusions Regardless of APOE genotypes and baseline cognitive function, habitual glucosamine use was significantly inversely associated with incident vascular dementia in the older population.

Abstract Objectives Lung adenocarcinoma (LUAD) exhibits a higher fatality rate among all cancer types worldwide, yet the precise mechanisms underlying its initiation and progression remain unknown. Mounting evidence suggests that long non-coding RNAs (lncRNAs) exert significant regulatory roles in cancer development and progression. Nevertheless, the precise involvement of lncRNA CYP4A22-AS1 in LUAD remains incompletely comprehended. Methods Bioinformatics analyses evaluated the expression level of CYP4A22-AS1 in lung adenocarcinoma and paracancer. The LUAD cell line with a high expression of CYP4A22-AS1 was constructed to evaluate the role of CYP4A22-AS1 in the proliferation and metastasis of LUAD by CCK8, scratch healing, transwell assays, and animal experiments. We applied transcriptome and microRNA sequencing to examine the mechanism of CYP4A22-AS1 enhancing the proliferation and metastasis of LUAD. Luciferase reporter gene analyses, west-blotting, and qRT-PCR were carried out to reveal the interaction between CYP4A22-AS1, miR-205-5p/EREG, and miR-34c-5p/BCL-2 axes. Results CYP4A22-AS1 expression was significantly higher in LUAD tissues than in the adjacent tissues. Furthermore, we constructed a LUAD cell line with a high expression of CYP4A22-AS1 and noted that the high expression of CYP4A22-AS1 significantly enhanced the proliferation and metastasis of LUAD. We applied transcriptome and microRNA sequencing to examine the mechanism of CYP4A22-AS1 enhancing the proliferation and metastasis of LUAD. CYP4A22-AS1 increased the expression of EREG and BCL-2 by reducing the expression of miR-205-5p and miR-34-5p and activating the downstream signaling pathway of EGFR and the anti-apoptotic signaling pathway of BCL-2, thereby triggering the proliferation and metastasis of LUAD. The transfection of miR-205-5p and miR-34-5p mimics inhibited the role of CYP4A22-AS1 in enhancing tumor progression. Conclusion This study elucidates the molecular mechanism whereby CYP4A22-AS1 overexpression promotes LUAD progression through the miR-205-5p/EREG and miR-34c-5p/BCL-2 axes.

Background: To analyze and compare the clinical efficacy of transumbilical single-incision laparoscopic surgery TAPP(SILS-TAPP) and conventional laparoscopic TAPP(CL-TAPP) in the treatment of senile inguinal hernia. Methods: From January 2019 to June 2021, a total of 221 elderly patients (≥60 years old) with inguinal hernia received SILS-TAPP and CL-TAPP in General Surgery Department of Affiliated Hospital of Nantong University. The perioperative indicators, postoperative complications and follow-up of the two groups were compared to explore the feasibility and superiority of SILS-TAPP in the treatment of inguinal hernia in the elderly. Results: There was no difference in demographic characteristics between the two groups. The mean operation time (28.6 ± 4.2 min vs 28.2 ± 5.3 min) in the SILS-TAPP group was not significantly different from that in the CL-TAPP group (Ρ = 0.623), and there was no significant increase in hospital costs(Ρ = 0.748). The intraoperative blood loss (7.4 ± 3.4 ml), VAS score on the postoperative day (2.2 ± 0.7), mean time of resuming activity (8.2 ± 1.9 h) and mean postoperative hospital stay (0.8 ± 0.2 d) in the SILS-TAPP group were better than those in the CL-TAPP group (Ρ

Runoff simulation is essential for effective water resource management and plays a pivotal role in hydrological forecasting. Improving the quality of runoff simulation and forecasting continues to be a highly relevant research area. The complexity of the terrain and the scarcity of long-term runoff observation data have significantly limited the application of Physically Based Models (PBMs) in the Qinghai–Tibet Plateau (QTP). Recently, the Long Short-Term Memory (LSTM) network has been found to be effective in learning the dynamic hydrological characteristics of watersheds and outperforming some traditional PBMs in runoff simulation. However, the extent to which the LSTM works in data-scarce alpine regions remains unclear. This study aims to evaluate the applicability of LSTM in alpine basins in QTP, as well as the simulation performance of transfer-based LSTM (T-LSTM) in data-scarce alpine regions. The Lhasa River Basin (LRB) and Nyang River Basin (NRB) were the study areas, and the performance of the LSTM model was compared to that of PBMs by relying solely on the meteorological inputs. The results show that the average values of Nash–Sutcliffe efficiency (NSE), Kling–Gupta efficiency (KGE), and Relative Bias (RBias) for B-LSTM were 0.80, 0.85, and 4.21%, respectively, while the corresponding values for G-LSTM were 0.81, 0.84, and 3.19%. In comparison to a PBM- the Block-Wise use of TOPMEDEL (BTOP), LSTM has an average enhancement of 0.23, 0.36, and −18.36%, respectively. In both basins, LSTM significantly outperforms the BTOP model. Furthermore, the transfer learning-based LSTM model (T-LSTM) at the multi-watershed scale demonstrates that, when the input data are somewhat representative, even if the amount of data are limited, T-LSTM can obtain more accurate results than hydrological models specifically calibrated for individual watersheds. This result indicates that LSTM can effectively improve the runoff simulation performance in alpine regions and can be applied to runoff simulation in data-scarce regions.

Abstract Background KDIGO and pRIFLE classifications are commonly used in pediatric acute kidney injury (AKI). As a novel AKI definition, pROCK considered the high variability of serum creatinine in children. This study aimed to compare the above three definitions for AKI in infants undergoing cardiac surgery. Methods We analyzed a clinical cohort of 413 infants undergoing cardiac surgery. AKI was defined and staged according to pRIFLE, KDIGO, and pROCK, respectively. Incidence differences and diagnostic agreement across definitions were assessed. The association between postoperative outcomes and AKI by each definition was investigated. Results Postoperative AKI was identified in 185 (44.8%), 160 (38.7%), and 77 (18.6%) patients according to pRIFLE, KDIGO, and pROCK, respectively. The agreement between pRIFLE and KDIGO was almost perfect (κ = 0.88), while there was only a slight agreement between pROCK and them. AKI by pROCK was independently associated with adverse outcomes (p = 0.003) and prolonged mechanical ventilation (p = 0.002). Conclusions There were considerable differences in AKI incidence and staging among definitions. Compared with pRIFLE and KDIGO, AKI defined by pROCK was significantly reduced and better associated with postoperative adverse outcomes.

Abstract Hyperhomocysteinemia (HHcy) is closely associated with thrombotic diseases such as myocardial infarction and stroke. Enhanced platelet activation was observed in animals and humans with HHcy. However, the influence of HHcy on thrombopoiesis remains largely unknown. Here, we reported increased platelet count (PLT) in mice and zebrafish with HHcy. In hypertensive patients (n = 11,189), higher serum level of total Hcy was observed in participants with PLT ≥ 291 × 109/L (full adjusted β, 0.59; 95% CI 0.14, 1.04). We used single-cell RNA sequencing (scRNA-seq) to characterize the impact of Hcy on transcriptome, cellular heterogeneity, and developmental trajectories of megakaryopoiesis from human umbilical cord blood (hUCB) CD34+ cells. Together with in vitro and in vivo analysis, we demonstrated that Hcy promoted megakaryocytes (MKs) differentiation via growth hormone (GH)-PI3K-Akt axis. Moreover, the effect of Hcy on thrombopoiesis is independent of thrombopoietin (TPO) because administration of Hcy also led to a significant increase of PLT in homozygous TPO receptor (Mpl) mutant mice and zebrafish. Administration of melatonin effectively reversed Hcy-induced thrombopoiesis in mice. ScRNA-seq showed that melatonin abolished Hcy-facilitated MK differentiation and maturation, inhibited the activation of GH-PI3K-Akt signaling. Our work reveals a previously unrecognized role of HHcy in thrombopoiesis and provides new insight into the mechanisms by which HHcy confers an increased thrombotic risk. Trial Registration clinicaltrials.gov Identifier: NCT00794885.

Abstract Background Prevention, screening, and early treatment are the aims of postoperative delirium management. The scoring system is an objective and effective tool to stratify potential delirium risk for patients undergoing cardiac surgery. Methods Patients who underwent cardiac surgery between January 1, 2012, and January 1, 2019, were enrolled in our retrospective study. The patients were divided into a derivation cohort (n = 45,744) and a validation cohort (n = 11,436). The AD predictive systems were formulated using multivariate logistic regression analysis at three time points: preoperation, ICU admittance, and 24 h after ICU admittance. Results The prevalence of AD after cardiac surgery in the whole cohort was 3.6% (2,085/57,180). The dynamic scoring system included preoperative LVEF ≤ 45%, serum creatinine > 100 µmol/L, emergency surgery, coronary artery disease, hemorrhage volume > 600 mL, intraoperative platelet or plasma use, and postoperative LVEF ≤ 45%. The area under the receiver operating characteristic curve (AUC) values for AD prediction were 0.68 (preoperative), 0.74 (on the day of ICU admission), and 0.75 (postoperative). The Hosmer‒Lemeshow test indicated that the calibration of the preoperative prediction model was poor (P = 0.01), whereas that of the pre- and intraoperative prediction model (P = 0.49) and the pre, intra- and postoperative prediction model (P = 0.35) was good. Conclusions Using perioperative data, we developed a dynamic scoring system for predicting the risk of AD following cardiac surgery. The dynamic scoring system may improve the early recognition of and the interventions for AD.

Background The prospective association of dietary thiamine intake with the risk of cognitive decline among the general older adults remains uncertain.Aims To investigate the association between dietary thiamine intake and cognitive decline in cognitively healthy, older Chinese individuals.Methods The study included a total of 3106 participants capable of completing repeated cognitive function tests. Dietary nutrient intake information was collected through 3-day dietary recalls and using a 3-day food-weighed method to assess cooking oil and condiment consumption. Cognitive decline was defined as the 5-year decline rate in global or composite cognitive scores based on a subset of items from the Telephone Interview for Cognitive Status–modified.Results The median follow-up duration was 5.9 years. There was a J-shaped relationship between dietary thiamine intake and the 5-year decline rate in global and composite cognitive scores, with an inflection point of 0.68 mg/day (95% confidence interval (CI): 0.56 to 0.80) and a minimal risk at 0.60–1.00 mg/day of dietary thiamine intake. Before the inflection point, thiamine intake was not significantly associated with cognitive decline. Beyond the inflection point, each unit increase in thiamine intake (mg/day) was associated with a significant decrease of 4.24 (95% CI: 2.22 to 6.27) points in the global score and 0.49 (95% CI: 0.23 to 0.76) standard units in the composite score within 5 years. A stronger positive association between thiamine intake and cognitive decline was observed in those with hypertension, obesity and those who were non-smokers (all p

Abstract Developing biomaterials with antimicrobial and wound‐healing activities for the treatment of wound infections remains challenging. Macrophages play non‐negligible roles in healing infection‐related wounds. In this study, a new sequential immunomodulatory approach is proposed to promote effective and rapid wound healing using a novel hybrid hydrogel dressing based on the immune characteristics of bacteria‐associated wounds. The hydrogel dressing substrate is derived from a porcine dermal extracellular matrix (PADM) and loaded with a new class of bioactive glass nanoparticles (BGns) doped with copper (Cu) and zinc (Zn) ions (Cu–Zn BGns). This hybrid hydrogel demonstrates a controlled release of Cu2+ and Zn2+ and sequentially regulates the phenotypic transition of macrophages from M1 to M2 by alternately activating nucleotide‐binding oligomerization domain (NOD) and inhibiting mitogen‐activated protein kinases (MAPK) signaling pathways. Additionally, its dual‐temporal bidirectional immunomodulatory function facilitates enhanced antibacterial activity and wound healing. Hence, this novel hydrogel is capable of safely and efficiently accelerating wound healing during infections. As such, the design strategy provides a new direction for exploring novel immunomodulatory biomaterials to address current clinical challenges related to the treatment of wound infections.

The current methods for detecting joints on tunnel face rely primarily on manual sketches, which are associated with issues of low detection efficiency and subjectivity. To address these concerns, this paper presents an intelligent recognition and segmentation algorithm based on Mask R-CNN (mask region-based convolutional neural network) for detecting joint targets on tunnel face images and automatically segmenting them, thereby improving detection efficiency and objectivity of the results. Additionally, to tackle the challenge of low detection accuracy in existing image processing methods, particularly for complex tunnel joint surfaces in dark environments, the paper introduces a path aggregation network (PANet) to enhance the fusion capability of feature information in Mask R-CNN, thereby improving the accuracy of the intelligent detection method. The algorithm was trained on a dataset of 800 tunnel face images, and the research findings demonstrate that it can quickly detect the position of joints on tunnel face images and assign masks to the joint pixel regions to achieve joint segmentation. The mean average precision (mAP) of the detection boxes and segmentation in the 80 test set images were 58.0% and 49.2%, respectively, which outperforms the original Mask R-CNN algorithm and other intelligent recognition and segmentation algorithms.

Abstract Central to homologous recombination (HR) is the assembly of Rad51 recombinase on single-strand DNA (ssDNA), forming the Rad51-ssDNA filament. How the Rad51 filament is efficiently established and sustained remains partially understood. Here, we find that the yeast ubiquitin ligase Bre1 and its human homolog RNF20, a tumor suppressor, function as recombination mediators, promoting Rad51 filament formation and subsequent reactions via multiple mechanisms independent of their ligase activities. We show that Bre1/RNF20 interacts with Rad51, directs Rad51 to ssDNA, and facilitates Rad51-ssDNA filament assembly and strand exchange in vitro. In parallel, Bre1/RNF20 interacts with the Srs2 or FBH1 helicase to counteract their disrupting effect on the Rad51 filament. We demonstrate that the above functions of Bre1/RNF20 contribute to HR repair in cells in a manner additive to the mediator protein Rad52 in yeast or BRCA2 in human. Thus, Bre1/RNF20 provides an additional layer of mechanism to directly control Rad51 filament dynamics.

Abstract In rice (Oryza sativa) tissue culture, callus can be induced from the scutellum in embryo or from the vasculature of non-embryonic organs such as leaves, nodes, or roots. Here we show that the auxin signaling pathway triggers cell division in the epidermis of the scutellum to form an embryo-like structure, which leads to callus formation. Our transcriptome data show that embryo-, stem cell-, and auxin-related genes are upregulated during scutellum-derived callus initiation. Among those genes, the embryo-specific gene OsLEC1 is activated by auxin and involved in scutellum-derived callus initiation. However, OsLEC1 is not required for vasculature-derived callus initiation from roots. In addition, OsIAA11 and OsCRL1, which are involved in root development, are required for vasculature-derived callus formation but not for scutellum-derived callus formation. Overall, our data indicate that scutellum-derived callus initiation is regulated by an embryo-like development program, and this is different from vasculature-derived callus initiation which borrows a root development program.

Abstract Cold and dense water from the North Pacific Ocean that spills through the Luzon Strait, the only deep conduit between the South China Sea (SCS) and the Pacific Ocean, renews deep-water mass, modulates hydrographic and biogeochemical cycles, and drives abyssal and overturning circulations in the SCS. The variability of this key oceanic process, however, has been poorly studied, mainly due to a lack of sustained observations. A comprehensive observational program that started in 2009 has provided 12 years of continuous time series of velocity and volume transport within the Luzon Strait. Here we show the observation-based assessment of decadal trends of deep-water transport through this vital passage. With the estimated 12-year mean volume transport of the deep-water overflow into the SCS of 0.84 ± 0.39 Sv (1 Sv = 106 m3 s−1), a significant linear upward trend of 9% is revealed during this period. This is consistent with long-term changes in satellite-observed ocean bottom pressure. The results of this study may have broad implications for the overturning circulations and biogeochemical processes, including carbon cycles in this region.

Abstract Background The individual and combined relations of handgrip strength and walking pace with the risk of chronic kidney disease (CKD) remain uncertain. We aimed to investigate the relationship of handgrip strength and/or walking pace with incident CKD, using data from the large‐scale, observational UK Biobank. Methods A total of 417 504 participants free of prior kidney diseases were included from UK Biobank. Handgrip strength was assessed by dynamometer. The walking pace was self‐reported as slow, average, or brisk. Cox proportional hazards models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CKD. Results The average age of the study population was 56.3 (SD, 8.1) years. 192 012 (46.0%) of the participants were male. The mean handgrip strength was 23.5 (SD, 6.2) and 40.0 (SD, 8.8) kg for females and males, respectively. Over a median follow‐up duration of 12.1 years, 11 064 (2.7%) participants developed incident CKD. Handgrip strength was significantly inversely associated with the risk of incident CKD in both males and females (both P for trend

TRIM72 oligomerization via intermolecular disulfide bonds is important for cells to repair damaged membranes. Here, authors report the crystal structure of TRIM72 dimer and show that TRIM72 B-box dimerization facilitates TRIM72 oligomerization.

Background: This study aimed to investigate the relationship of residential green and blue spaces with incident nonalcoholic fatty liver disease (NAFLD), and explore the potential mediation effects of air pollutants and modification effect of genetic susceptibility. Methods: 411,200 UK Biobank participants without prior liver diseases were included. Land use data were used to estimate residential green and blue spaces (land coverage percentage) at 300 m and 1000 m buffer. The study outcome was incident NAFLD, ascertained through linkage to hospital admissions and death registry records. Results: 5198 NAFLD cases were documented after a median follow-up of 12.5 years. Green and blue spaces were inversely associated with the hazard of NAFLD: per standard deviation (SD) increment of green space coverage at 300 m (SD: 14.5 %; HR, 0.88, 95 %CI, 0.86–0.91) and 1000 m (SD: 14.1 %; HR, 0.88, 95 %CI, 0.86–0.91) buffer, and blue space coverage at 300 m (SD: 1.0 %; HR,0.95, 95 %CI, 0.93–0.98) and 1000 m (SD: 1.2 %; HR,0.96, 95 %CI, 0.93–0.99) buffer were related with a 4–12 % reduction of NAFLD incidence. The beneficial effects of approximately 25–52 % of green space exposure and about 5–35 % of blue space exposure on NAFLD incidence were mediated by the reduction of PM2.5, NO2 and NOx (All P indirect effect

Abstract A significant portion (∼2.1 Sv, 1 Sv = 106 m3 s−1) of deep water penetrates into the Philippine Sea through the Yap‐Mariana Junction, the sole passage of the Philippine Sea below 4,000 m, and is then upwelled into shallower layers, closing regional overturning circulation. Yet, the structure and variability of this diapycnal upwelling remain poorly understood. Here, we report on a fine‐resolution hydrographic observation conducted at the most significant topographic feature in the Philippine Sea, the Kyushu‐Palau Ridge (KPR). Enhanced mixing up to O(10−2) m2 s−1 near the KPR is manifested, indicating the presence of substantial upwelling herein. Besides, the ridge‐related topography contributes more deep‐water mass transformation than abyssal basins in the Philippine Sea. This study highlights the significant role of rough bathymetry features in generating diapycnal upwelling in the North Pacific.

Abstract The cold dense water from the Pacific sinks to the deep South China Sea (SCS) through the Luzon Strait, driving the abyssal and overturning circulations in the SCS, and affecting the Indonesia Throughflow and its associated heat and freshwater fluxes. Combining the ocean bottom pressure data and the hydrographic data, we reveal the seasonal link between Luzon Strait deepwater overflow (LSDO) and deep western boundary current (DWBC) in the Philippine Sea. The seasonal variation in the DWBC dominates the pressure difference between the Pacific and the SCS by adjusting the temperature field on the east side of the Luzon Strait, which in turn contributes to the seasonal variation in the LSDO. The enhanced DWBC in summer/autumn carries more relatively cold water from the high latitudes to the east of the Luzon Strait, increasing the local density and leading to the enhancement of the LSDO in autumn.

Abstract The robust and stable expression of CD38 in T‐cell acute lymphoblastic leukemia (T‐ALL) blasts makes CD38 chimeric antigen receptor (CAR)‐T/natural killer (NK) a potential therapy for T‐ALL. However, CD38 expression in normal T/NK cells causes fratricide of CD38 CAR‐T/NK cells. Here a “2‐in‐1” gene editing strategy is developed to generate fratricide‐resistant locus‐specific CAR‐T/NK cells. CD38‐specific CAR is integrated into the disrupted CD38 locus by CRISPR/Cas9, and CAR is placed under the control of either endogenous CD38 promoter (CD38KO/KI) or exogenous EF1α promoter (CD38KO/KIEF1α). CD38 knockout reduces fratricide and allows the expansion of CAR‐T cells. Meanwhile, CD38KO/KIEF1α results in higher CAR expression than CD38KO/KI in both CAR‐T and CAR‐NK cells. In a mouse T‐ALL model, CD38KO/KIEF1α CAR‐T cells eradicate tumors better than CD38KO/KI CAR‐T cells. Surprisingly, CD38KO/KI CAR‐NK cells show superior tumor control than CD38KO/KIEF1α CAR‐NK cells. Further investigation reveals that endogenous regulatory elements in NK cells lead to higher expression of CD38 CAR than in T cells, and the expression levels of CAR affect the therapeutic outcome of CAR‐T and CAR‐NK cells differently. Therefore, these results support the efficacy of CD38 CAR‐T/NK against T‐ALL and demonstrate that the “2‐in‐1” strategy can resolve fratricide and enhance tumor eradication, paving the way for clinical translation.

Background The association of a healthy lifestyle with the prognosis of type 2 diabetes remains uncertain. We aimed to evaluate the associations of a healthy lifestyle and a higher American Heart Association's Life's Essential 8 score with incident macrovascular and microvascular diseases in type 2 diabetes. Methods and Results A total of 13 543 participants with baseline type 2 diabetes and free of macrovascular and microvascular diseases from the UK Biobank were included. A healthy lifestyle was determined based on body mass index, smoking, alcohol consumption, physical activity, sleep duration, and diet. Life's Essential 8 scores were generated from 8 metrics according to the American Heart Association's cardiovascular health advisory, ranging from 0 to 100. During a median follow‐up of 12.1 years, 3279 (24.2%) incident macrovascular diseases and 2557 (18.9%) microvascular diseases were documented. Compared with those with a poor lifestyle, participants with an ideal lifestyle had significantly lower risks of incident macrovascular disease (hazard ratio [HR], 0.46 [95% CI, 0.36–0.59]) and microvascular disease (HR, 0.60 [95% CI, 0.47–0.77]). Significantly lower risks of macrovascular disease (HR, 0.20 [95% CI, 0.05‐0.79]) and microvascular disease (HR, 0.24 [95% CI, 0.06‐0.98]) were also found in the high cardiovascular health group (Life's Essential 8 scores: 80–100), compared to the low cardiovascular health group (scores: 0–49). Adhering to an ideal lifestyle may prevent 37.0% of macrovascular disease and 24.7% of microvascular disease, and attaining a high cardiovascular health may prevent 71.9% of macrovascular disease and 67.5% of microvascular disease. Conclusions A healthy lifestyle and a higher Life's Essential 8 score were associated with lower risks of macrovascular and microvascular diseases among participants with type 2 diabetes.

The heterotrimeric Replication protein A (RPA) is the ubiquitous eukaryotic single-stranded DNA (ssDNA) binding protein and participates in nearly all aspects of DNA metabolism, especially DNA damage response. The N-terminal OB domain of the RPA70 subunit (RPA70N) is a major protein-protein interaction element for RPA and binds to more than 20 partner proteins. Previous crystallography studies of RPA70N with p53, DNA2 and PrimPol fragments revealed that RPA70N binds to amphipathic peptides that mimic ssDNA. NMR chemical-shift studies also provided valuable information on the interaction of RPA70N residues with target sequences. However, it is still unclear how RPA70N recognizes and distinguishes such a diverse group of target proteins. Here, we present high-resolution crystal structures of RPA70N in complex with peptides from eight DNA damage response proteins. The structures show that, in addition to the ssDNA mimicry mode of interaction, RPA70N employs multiple ways to bind its partners. Our results advance the mechanistic understanding of RPA70N-mediated recruitment of DNA damage response proteins.

Background: The relationship of air pollutants and residential exposure to greenspace with severe liver disease remains inconclusive. Objective: Our objective was to assess the relationship of joint exposure to air pollutants, residential exposure to greenspaces with new-onset severe liver disease. Methods: We included 427,697 participants without prior liver diseases from UK Biobank. A weighted air pollution score was calculated based on PM2.5, PM10, PM2.5–10, NO2, and NOX. The percentage of land coverage by residential greenspaces was estimated using land use data. The primary outcome was new-onset severe liver disease, defined as a composite outcome including hospitalization or death due to compensated or decompensated liver cirrhosis, liver failure, and hepatocellular carcinoma. Results: During a median follow-up of 12.0 years, 4572 participants developed severe liver disease. A higher air pollution score was significantly associated with an increased risk of new-onset severe liver disease (per SD increment; adjusted hazard ratio [HR],1.07; 95% confidence interval [CI],1.04–1.10). Moreover, residential greenspace coverage was inversely associated with new-onset severe liver disease (per SD increment; adjusted HR, 0.95; 95% CI,0.92–0.98). Genetic risks of liver cirrhosis did not significantly modify the associations (both P-interactions >0.05). However, we observed a stronger positive association between air pollution scores and new-onset severe liver disease in individuals with higher fibrosis-4 (FIB-4) scores, lower residential greenspaces, hypertension, and smokers (all P-interactions

Abstract Background The relations of the variety and quantity of different sources of dietary insoluble fibers and hypertension remain uncertain. We aimed to investigate the associations between the variety and quantity of insoluble fibers intake from six major food sources and new-onset hypertension, using data from the China Health and Nutrition Survey (CHNS). Methods Twelve thousand one hundred thirty-one participants without hypertension at baseline from CHNS were included. Dietary intake was measured by three consecutive 24-h dietary recalls combined with a household food inventory. The variety score of insoluble fiber sources was defined as the number of insoluble fiber sources consumed at the appropriate level, accounting for both types and quantities of insoluble fibers. The study outcome was new-onset hypertension, defined as blood pressure ≥ 140/90 mmHg, or physician-diagnosed hypertension or receiving antihypertensive treatments during the follow-up. Results During a median follow-up of 6.1 years, 4252 participants developed hypertension. There were L-shaped associations of dietary insoluble fibers derived from vegetables, beans, tubers, and fruits with new-onset hypertension; a reversed J-shaped association of whole grain-derived insoluble fiber with new-onset hypertension; and no obvious association of refined grain-derived insoluble fiber with new-onset hypertension. Therefore, refined grain was not included in the insoluble fiber variety score calculation. More importantly, a higher insoluble fiber variety score was significantly associated with lower risks of new-onset hypertension (per score increment, hazard ratio, 0.50; 95% CI, 0.45–0.55). Conclusions There was an inverse association between the variety of insoluble fibers with appropriate quantity from different food sources and new-onset hypertension.

Rapid and accurate inversion of soil salinity is a key scientific problem that needs to be solved urgently. Due to the accuracy of UAV multispectral remote sensing inversion of salinity based on back propagation neural network (BPNN) is low, in this study, used the UAV multispectral image and field measurements of 60 soil surface salinity as data sources, 16 salinity indexs were constructed using the extracted spectral reflectance, and performed a gray relation analysis to screen salinity index features after applying a film removal to construct the BPNN salinity inversion model. Particle swarm optimization (PSO), thinking evolutionary algorithm (MEA), and genetic algorithm (GA) were applied to optimize the BPNN inverse model, respectively, and the optimization capabilities of the four algorithms were compared and evaluated to optimize the best optimization algorithm. The results showed that the GRA variable screening can effectively remove the redundant information of spectral parameters and reduce the complexity of the salinity inversion model; the PSO, MEA, and GA can effectively improve the robusticity of BPNN inversion model, and GA algorithm has the best optimization effect in terms of inverse model optimization effect, followed by MEA and PSO algorithms; the accuracy of the PSO-BPNN, MEA-BPNN, and GA-BPNN inversion models are better than that of the BPNN model, and GA-BPNN is the best salinity inversion model, which achieves R2 of 0.6659, RMSE of 0.0751, and RPD of 2.0211. This approach can effectively solve salinity monitoring accuracy issues of UAV multispectral inversion.

Abstract Background The independent and additive associations of walking pace and grip strength on dementia risk and the potential modifying effects of age, APOE phenotypes, and other dementia risk factors on the walking pace and dementia relationships demand further clarification. We aimed to investigate the independent and additive relationships of walking pace and handgrip strength on the risk of new-onset dementia and examine the potentially modifying effects of age, APOE phenotypes, lifestyle factors, and family history of dementia in the relationships. Methods A total of 495,700 participants from the UK Biobank, who were free of dementia at baseline, were included in this study. Walking pace was self-defined as slow, average, or brisk. Handgrip strength was assessed by dynamometer and was divided into sex-specific quartiles. The APOE genotypes were determined by a combination variant of rs429358 and rs7412. Other dementia risk factors, including education, physical activity, hypertension, depression, diabetes, and family history of dementia, were also collected. The primary outcome was new-onset all-cause dementia. Results Over a median follow-up duration of 12.0 years, 3986 (0.8%) participants developed new-onset all-cause dementia. Compared with those with slow walking pace, participants with average (HR, 0.61; 95%CI: 0.55–0.68) or brisk (HR, 0.59; 95%CI: 0.52–0.67) walking pace had a significantly lower risk of new-onset all-cause dementia. Moreover, compared with those with both slow walking pace and lower handgrip strength (the first quartile), the lowest risk of new-onset all-cause dementia was observed in participants with both average or brisk walking pace and higher handgrip strength (the 2–4 quartiles) (HR, 0.45; 95%CI: 0.40–0.52). Notably, the negative relationship between walking pace and the risk of new-onset all-cause dementia was significantly reduced as APOE ε4 dosage increased (APOE ε4 dosages = 0 or 1: brisk vs. slow: HR, 0.55; 95%CI: 0.48–0.63; vs. APOE ε4 dosages = 2: brisk vs. slow: HR, 1.14; 95%CI: 0.77–1.68; P for interaction = 0.001) or age increased (

Abstract Background We aimed to investigate the joint effect of visit-to-visit variability (VVV) in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides and glycosylated hemoglobin (HbA1c) on cardiovascular mortality and total mortality in patients with diabetes. Methods Among 5194 participants with type 2 diabetes enrolled in the ACCORD lipid trial, VVVs of LDL-C, triglycerides, HDL-C, and HbA1c were assessed from baseline to 2 years of follow-up and expressed as coefficient of variation (CV). The study outcomes included cardiovascular mortality and all-cause mortality. Results Over a median follow-up of 3.0 years from the end of variability measurements at years 2, there were 305 (5.9%) cases of all-cause mortality, of which, 144 were cardiovascular causes. The positive relations between LDL-C CV and cardiovascular mortality were significantly stronger among participants with higher HDL-C CV (P for interaction = 0.023), and higher HbA1c CV (P for interaction = 0.015). However, there were no significant interactions between LDL-C CV and triglycerides CV (P for interaction = 0.591). Similar trends were found for all-cause mortality. Consistently, there were graded trends in the risk of mortality with the increasing numbers of higher CV of the three variables: LDL-C, HbA1c, and HDL-C (P for trend = 0.008 for cardiovascular mortality, and P for trend

Highlights 1. Glucosamine use was associated with lower risk of incident gout in females. 2. The inverse association between glucosamine use and gout was stronger in females with diuretics use. 3. Gout genetic risk scores did not significantly modify the association.

Accurate segmentation of the medical image is the basis and premise of intelligent diagnosis and treatment, which has a wide range of clinical application value. However, the robustness and effectiveness of medical image segmentation algorithms remains a challenging subject due to the unbalanced categories, blurred boundaries, highly variable anatomical structures and lack of training samples. For this reason, we present a parallel dilated convolutional network (PDC-Net) to address the pituitary adenoma segmentation in magnetic resonance imaging images. Firstly, the standard convolution block in U-Net is replaced by a basic convolution operation and a parallel dilated convolutional module (PDCM), to extract the multi-level feature information of different dilations. Furthermore, the channel attention mechanism (CAM) is integrated to enhance the ability of the network to distinguish between lesions and non-lesions in pituitary adenoma. Then, we introduce residual connections at each layer of the encoder-decoder, which can solve the problem of gradient disappearance and network performance degradation caused by network deepening. Finally, we employ the dice loss to deal with the class imbalance problem in samples. By testing on the self-established patient dataset from Quzhou People’s Hospital, the experiment achieves 90.92% of Sensitivity, 99.68% of Specificity, 88.45% of Dice value and 79.43% of Intersection over Union (IoU).

ObjectiveTo explore the changes in dynamic functional brain network connectivity (dFNC) in patients with early-onset bipolar disorder (BD).MethodsResting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 39 patients with early-onset BD and 22 healthy controls (HCs). Four repeated and stable dFNC states were characterised by independent component analysis (ICA), sliding time windows and k-means clustering, and three dFNC temporal metrics (fraction of time, mean dwell time and number of transitions) were obtained. The dFNC temporal metrics and the differences in dFNC between the two groups in different states were evaluated, and the correlations between the differential dFNC metrics and neuropsychological scores were analysed.ResultsThe dFNC analysis showed four connected patterns in all subjects. Compared with the HCs, the dFNC patterns of early-onset BD were significantly altered in all four states, mainly involving impaired cognitive and perceptual networks. In addition, early-onset BD patients had a decreased fraction of time and mean dwell time in state 2 and an increased mean dwell time in state 3 (p 0.05 after Bonferroni correction).ConclusionPatients with early-onset BD had abnormal dynamic properties of brain functional network connectivity, suggesting that their dFNC was unstable, mainly manifesting as impaired coordination between cognitive and perceptual networks. This study provided a new imaging basis for the neuropathological study of emotional and cognitive deficits in early-onset BD.

Abstract Birefringence, which modulates the polarization of electromagnetic wave, has been commercially developed and widely used in modern photonics. Fostered by high‐frequency signal processing and communications, feasible birefringence technologies operating in gigahertz (GHz) range are highly desired. Here, a coherent phonon‐induced GHz optical birefringence and its manipulation in SrTiO3 (STO) crystals are demonsrated. With ultrafast laser pumping, the coherent acoustic phonons with low damping are created in the transducer/STO structures. A series of transducer layers are examined and the optimized one with relatively high photon–phonon conversion efficiency, i.e., semiconducting LaRhO3 film, is obtained. The most intriguing finding here is that, by virtue of high sensitivity to strain perturbation of STO, GHz optical birefringence can be induced by the coherent acoustic phonons and the birefringent amplitudes possess crystal orientation dependence. Optical manipulation of both coherent phonons and its induced GHz birefringence by double pump technique are also realized. These findings reveal an alternative mechanism of ultrafast optical birefringence control, and offer prospects for applications in high‐frequency acoustic‐optics devices.

Abstract Background Studies on the prospective association of body composition with mortality in US general populations are limited. We aimed to examine this association by utilizing data from the National Health and Nutrition Examination Survey (NHANES), a representative sample of US adults, linked with data from the National Death Index. Methods We analysed data of NHANES 1988–1994 and 1999–2014, with 55 818 participants [50.6% female, baseline mean age: 45.0 years (SE, 0.2)]. Predicted fat mass and lean mass were calculated using the validated sex‐specific anthropometric prediction equations developed by the NHANES based on individual age, race, height, weight, and waist circumference. Body composition and other covariates were measured at only one time point. Multivariable Cox regression was used to investigate the associations of predicted fat mass and lean mass with overall and cause‐specific mortality, adjusting for potential confounders. Interactions between age and body composition on mortality were examined with likelihood ratio testing. Results Mean predicted fat mass was 24.1 kg [95% confidence interval (CI): 23.9–24.3) for male participants and 29.9 kg (95% CI: 29.6–30.1) for female participants, while mean predicted lean mass was 59.3 kg (95% CI: 59.1–59.5) for male participants and 41.7 kg (95% CI: 41.5–41.8) for female participants. During a median period of 9.7 years from the survey, 10 408 deaths occurred. When predicted fat and lean mass were both included in the model, predicted fat mass showed a U‐shaped association with all‐cause mortality, with significantly higher risk at two ends: Quintile 1 (HR, 1.17; 95% CI: 1.05–1.31), Quintile 2 (HR, 1.14; 95% CI: 1.04–1.26) and Quintile 5 (HR, 1.37; 95% CI: 1.12–1.68) compared with Quintile 3. In contrast, predicted lean mass showed a L‐shaped association with all‐cause mortality, with higher mortality in those with lower lean mass: Quintile 1 (HR, 1.64; 95% CI: 1.46–1.83) and Quintile 2 (HR, 1.29; 95% CI: 1.18–1.42) compared with Quintile 3. Similar results were found for cardiovascular, cancer, and respiratory cause‐specific mortality. Age was a significant modifier: There was a monotonic positive association of predicted fat mass with mortality in younger participants (

Abstract Background The relation of the variety and quantity of different sources of dietary proteins intake and diabetes remains uncertain. We aimed to investigate the associations between the variety and quantity of proteins intake from eight major food sources and new-onset diabetes, using data from the China Health and Nutrition Survey (CHNS). Methods 16,260 participants without diabetes at baseline from CHNS were included. Dietary intake was measured by three consecutive 24-h dietary recalls combined with a household food inventory. The variety score of protein sources was defined as the number of protein sources consumed at the appropriate level, accounting for both types and quantity of proteins. New-onset diabetes was defined as self-reported physician-diagnosed diabetes or fasting glucose ≥7.0mmol/L or glycated hemoglobin ≥6.5% during the follow-up. Results During a median follow-up of 9.0 years, 1100 (6.8%) subjects developed diabetes. Overall, there were U-shaped associations of percentages energy from total protein, whole grain-derived and poultry-derived proteins with new-onset diabetes; J-shaped associations of unprocessed or processed red meat-derived proteins with new-onset diabetes; a reverse J-shaped association of the fish-derived protein with new-onset diabetes; L-shaped associations of egg-derived and legume-derived proteins with new-onset diabetes; and a reverse L-shaped association of the refined grain-derived protein with new-onset diabetes (all P values for nonlinearity

Objective: To examine the associations of mobile phone use and its use characteristics with new-onset CKD.Methods: 408,743 participants without prior CKD in the UK Biobank were included. The primary outcome was new-onset CKD.Results: During a median follow-up of 12.1 years, 10,797 (2.6%) participants occurred CKD. Compared with mobile phone non-users, a significantly higher risk of new-onset CKD was found in mobile phone users (HR = 1.07; 95% CI: 1.02–1.13). Moreover, among mobile phone users, compared with participants with weekly usage time of mobile phone making or receiving calls

Quantum conference key agreement (QCKA) allows multiple users to distribute secret conference keys over long distances. Measurement-device-independent QCKA (MDI-QCKA) is an effective QCKA scheme, which closes all detection loopholes and greatly enhances QCKA’s security in practical application. However, an eavesdropper (Eve) may compromise the security of practical systems and acquire conference key information by taking advantage of the weak randomness from the imperfect quantum devices. In this article, we analyze the performance of the MDI-QCKA scheme based on the weak randomness model. Our simulation results show that even a small proportion of weak randomness may lead to a noticeable fluctuation in the conference key rate. For the case with finite-key size, we find that the weak randomness damages the performance of MDI-QCKA to different degrees according to the data size of total pulses transmitted. Furthermore, we infer that QCKA based on single-photon interference technology may perform better in resisting weak randomness vulnerabilities. Our work contributes to the practical security analysis of multiparty quantum communication and takes a further step in the development of quantum networks.

Background Understanding the natural history of elevated blood pressure (BP) is important to determine the window for primary prevention of hypertension. The authors aimed to investigate the natural history of elevated BP and examine whether there were inflection points in BP trajectories preceding hypertension onset in Chinese adults. Methods and Results A total of 8688 participants with an average of 5 BP measurements were included from the CHNS (China Health and Nutrition Survey). In each wave, triplicate measurements on the same arm were taken, and the mean systolic BP (SBP) and diastolic BP (DBP) were used in the analysis. Hypertension onset was defined as SBP ≥140 mm Hg or DBP ≥90 mm Hg or diagnosed by physician or currently under antihypertensive treatment. The median follow‐up time was 13.0 years. Overall, BP elevation with age prior to the onset of hypertension showed a nonlinear trajectory. The increased rates in both SBP and DBP were obviously faster after the inflection point than before. According to hypertension onset at age 30 to 39, 40 to 49, 50 to 59, 60 to 69, and 70 to 79 years, at the inflection point, patients were ≈29, 38, 48, 57, and 67 years, SBP levels were 112.6, 114.8, 116.8, 117.4, and 118.0 mm Hg, and DBP levels were 73.4, 75.7, 76.9, 76.2, and 73.8 mm Hg, respectively. Conclusions There was a nonlinear trajectory of BP elevation preceding hypertension onset. The inflection points for SBP and DBP were in the range of 112 to 118 mm Hg and 73 to 77 mm Hg, respectively. Once BP levels exceeded the changing points, the level of SBP and DBP increased more rapidly.