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Abstract Essential oils (EOs) are complex and susceptible to environmental conditions, they have a wide range of biological activities and are often used to differentiate between similar species. In this study, gas chromatography-mass spectrometry (GC–MS) coupled with chemometric analysis was applied to systematically analyse and evaluate EOs constituents and antioxidant activity of six Chinese Cupressaceae taxa (Platycladus orientalis Franco, P. orientalis Franco ‘Sieboldii’, P. orientalis Franco ‘Aurea’, Juniperus chinensis Roxb., J. chinensis Roxb. ‘Kaizuca’, and J. sabina L.) under identical conditions. The antioxidant activity of the EOs was evaluated using 2,2 -diphenyl-1-picrylhydrazyl (DPPH), 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and ferric reducing power (FRAP), and the total phenolic content (TPC) of the EOs was determined by Folin–Ciocalteau reagent. In total, seventy individual constituents were identified with the main components being α-pinene, sabinene, d-limonene, bornyl acetate, δ-3-carene and β-myrcene. Principal component analysis (PCA) and hierarchal cluster analysis (HCA) successfully discriminated the six taxa into three chemotypes and the unique chemotype revealed that J. chinensis ‘Kaizuca’ may be a species rather than a cultivar of J. chinensis. The results of OPLS-DA analysis showed that the three compounds screened, namely, α-pinene, sabinene, and δ-3-carene, can completely distinguish Platycladus spp. from Juniperus spp. The DPPH assay results ranged from 576.14 (J. chinensis ‘Kaizuca’) to 1146.12 (J. sabina) μmol eq Trolox/mL EO, while the ABTS values ranged from 1579.62 (P. orientalis ‘Aurea’) to 5071.82 (J. sabina) μmol eq Trolox/mL. In the FRAP assay, the values ranged from 1086.50 (J. chinensis ‘Kaizuca’) to 1191.18 (J. sabina) μmol eq Trolox/ml and the TPC of the EOs studied ranged from 15.17 (J. chinensis ‘Kaizuca’) to 39.37 (J. sabina) mg GAE/mL EO. The results consistently showed that J. sabina possessed the strongest antioxidant activity and can be preferentially used as a rich source of potentially natural antioxidants.

Abstract Background Malnutrition is common in patients with chronic cardiovascular disease and is associated with significantly higher all-cause mortality. Approximately one-third of patients with heart failure are malnourished. However, the relationship between malnutrition and idiopathic pulmonary arterial hypertension (IPAH) remains unclear. This study aimed to clarify the prognostic value of malnutrition in patients with IPAH. Methods A total of 432 consecutive participants with IPAH were included in this study between March 2013 and August 2021. Three common malnutrition assessment tools, including the geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), and controlling nutritional status (CONUT) score, were used to evaluate the nutritional status of patients with IPAH. The relationships between the malnutrition tools and long-term adverse outcomes were determined using restricted cubic splines and multivariate Cox regression models. Results During a mean follow-up of 3.1 years, 158 participants experienced clinical worsening or all-cause death. Patients were stratified into the low-, intermediate- and high-risk groups based on the European Society of Cardiology (ESC) risk stratification, and the PNI (55.9 ± 5.7 vs. 54.4 ± 7.2 vs. 51.1 ± 7.1, P = 0.005) and CONUT score (2.1 ± 0.9 vs. 2.5 ± 1.2 vs. 3.3 ± 1.1, P

Abstract Hybrid mapping is a powerful approach to efficiently identify and characterize genes regulated through mechanisms in cis. In this study, using reciprocal crosses of the phenotypically divergent Duroc and Lulai pig breeds, we perform a comprehensive multi-omic characterization of regulatory variation across the brain, liver, muscle, and placenta through four developmental stages. We produce one of the largest multi-omic datasets in pigs to date, including 16 whole genome sequenced individuals, as well as 48 whole genome bisulfite sequencing, 168 ATAC-Seq and 168 RNA-Seq samples. We develop a read count-based method to reliably assess allele-specific methylation, chromatin accessibility, and RNA expression. We show that tissue specificity was much stronger than developmental stage specificity in all of DNA methylation, chromatin accessibility, and gene expression. We identify 573 genes showing allele specific expression, including those influenced by parent-of-origin as well as allele genotype effects. We integrate methylation, chromatin accessibility, and gene expression data to show that allele specific expression can be explained in great part by allele specific methylation and/or chromatin accessibility. This study provides a comprehensive characterization of regulatory variation across multiple tissues and developmental stages in pigs.

Abstract Background Cholestasis is a common yet severe complication that occurs during the advancement of liver metastasis. However, how cholestasis impacts the development, treatment, and tumor microenvironment (TME) of liver metastasis remains to be elucidated. Methods Extrahepatic and intrahepatic cholestatic mouse models with liver metastasis were established to detect the differential expression levels of genes, infiltration of immune cells and change in bile acid-associated metabolites by using RNA-Sequencing, flowcytometry, and liquid chromatography and mass spectrometry. Western blot was applied to neutrophils under the stimulation of primary bile acids (BAs) in vitro to study the mechanism of phenotypic alteration. In vitro coculture of BA-treated neutrophils with CD8+ T cells were performed to study the immune-suppressive effect of phenotypic-altered neutrophils. Clinical samples collected from colorectal cancer patients with liver metastasis and cholestasis were applied to RNA-Seq. Results Compared to non-cholestatic mice, the progression of liver metastasis of cholestatic mice was significantly accelerated, which was associated with increased neutrophil infiltration and T-cell exclusion. Both neutrophils and T cells expressed higher immunosuppressive markers in the cholestatic mouse model, further indicating that an immunosuppressive tumor microenvironment was induced during cholestasis. Although neutrophils deletion via anti-Ly6G antibody partially hindered liver metastasis progression, it reduced the overall survival of mice. Tauro-β-muricholic acid (Tβ-MCA) and Glycocholic acid (GCA), the two most abundant cholestasis-associated primary BAs, remarkably promoted the expression of Arg1 and iNOS on neutrophils via p38 MAPK signaling pathway. In addition, BAs-pretreated neutrophils significantly suppressed the activation and cytotoxic effects of CD8+ T cells, indicating that the immunosuppressive phenotype of neutrophils was directly induced by BAs. Importantly, targeting BA anabolism with Obeticholic acid (OCA) under cholestasis effectively suppressed liver metastasis progression, enhanced the efficacy of immune checkpoint blockade, and prolonged survival of mice. Conclusions Our study reveals the TME of cholestasis-associated liver metastasis and proposes a new strategy for such patients by targeting bile acid anabolism. Graphical Abstract Schematic model depicting the proposed mechanism of cholestasis-mediated progression of colorectal liver metastasis. As cholestasis progresses, excessive primary bile acids that accumulate in the liver intoxicates hepatocytes, which lead to exacerbated release of chemokines, particularly CXCL2 and CXCL5. Neutrophils are then accumulated by CXCL2 and CXCL5 and undergo an immunosuppressive-phenotypic alteration induced by direct stimulation of BAs via activating the p38 MAPK signaling pathway, which eventually led to the dysfunction of T cells and progression of LM. Targeting bile acid anabolism can effectively restore the immune-activated microenvironment and prevent the progression of LM.

Abstract Interregional grain trade affects the environment while balancing supply and demand. However, what relationship exist between national carbon emissions reduction and nitrogen losses reduction in each export region is unclear. Here we used maize as a case study to address this gap by combining life cycle assessment method with linear programming model. We found that interprovincial maize trade can reduce the country’s overall carbon emissions and nitrogen losses. However, the carbon and nitrogen reduction potential varied across exporting provinces. Northeast provinces have great potential to reduce the country’s overall carbon emissions and nitrogen losses via interprovincial maize trade. Northwest provinces increase the overall carbon emissions but reduce the overall nitrogen losses when transferring out maize. Optimizing interprovincial maize trade schemes can further enhance the country’s overall carbon and nitrogen reduction potential. The research results provide a theoretical reference for China to develop carbon neutral and nitrogen reduction trade schemes.

Abstract Peroxisomal l-bifunctional enzyme (EHHADH) plays a role in the classic peroxisomal fatty acid β-oxidation pathway; however, the relationship between EHHADH expression and diabetic kidney disease has not been well understood. Here, we found that endogenous EHHADH levels were strongly correlated with the progression and severity of diabetic nephropathy in T2D patients. EHHADH knockout mice exhibited worsened renal tubular injury in diabetic mice. Furthermore, EHHADH is a modulator of pexophagy. In renal tubular epithelial cells (RTECs) in vitro, the knockdown of EHHADH induced a dramatic loss of peroxisomes. The loss of peroxisomes in EHHADH-deficient RTECs was restored by either an autophagic inhibitor 3-methyladenine or bafilomycin A1 both in vitro and in vivo. NBR1 was required for pexophagy in EHHADH-knockdown cells, where the level of reactive oxygen species (ROS) was increased, while inhibition of ROS blocked pexophagy. In summary, our findings revealed EHHADH deficiency accelerated renal injury in DKD as a modulator of pexophagy.

Abstract Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive pulmonary vascular disorder with substantial morbidity and mortality, also a disease underdiagnosed and undertreated. It is potentially curable by pulmonary endarterectomy (PEA) in patients with surgically accessible thrombi. Balloon pulmonary angioplasty (BPA) and targeted medical therapy are options for patients with distal lesions or persistent/recurrent pulmonary hypertension after PEA. There is an urgent need to increase the awareness of CTEPH. Qualified CTEPH centers are still quite limited. Baseline characteristics, management pattern and clinical outcome of CTEPH in China needs to be reported. Methods and design The CHinese reAl-world study to iNvestigate the manaGEment pattern and outcomes of chronic thromboembolic pulmonary hypertension (CHANGE) study is designed to provide the multimodality treatment pattern and clinical outcomes of CTEPH in China. Consecutive patients who are ≥ 14 year-old and diagnosed with CTEPH are enrolled. The diagnosis of CTEPH is confirmed in right heart catheterization and imaging examinations. The multimodality therapeutic strategy, which consists of PEA, BPA and targeted medical therapy, is made by a multidisciplinary team. The blood sample and tissue from PEA are stored in the central biobank for further research. The patients receive regular follow-up every 3 or 6 months for at least 3 years. The primary outcomes include all-cause mortality and changes in functional and hemodynamic parameters from baseline. The secondary outcomes include the proportion of patients experiencing lung transplantation, the proportion of patients experiencing heart and lung transplantation, and changes in health-related quality of life. Up to 31 December 2023, the study has enrolled 1500 eligible patients from 18 expert centers. Conclusions As a real-world study, the CHANGE study is expected to increase our understanding of CTEPH, and to fill the gap between guidelines and the clinical practice in the diagnosis, assessment and treatment of patients with CTEPH. Registration Number in ClinicalTrials.gov NCT05311072.

In the present study, laser welding of medium-thick TWIP steel plates was studied and the microstructures and mechanical properties of the welded joints obtained at varied welding speeds were characterized. It is shown that a full penetration was achieved in the welded joint, which exhibits a keyhole-shaped configuration. The welded joint displays a single austenitic phase and typical solidification structure composed of cellular, columnar and dendrite grains. With increasing the welding speed, the grains in both the central fusion zone and adjacent heat-affected zone were refined. The latter was attributed to inadequate recrystallization because of decreased heating time at elevated welding speed. The mechanical properties of all welded joints were lower than those of base metal, in which the decline of elongation was more serious than that of strength. This is attributed to the formation of thick columnar crystals and the Al2O3 core-shell structured nanoscale precipitates in the grains of the fusion zone. Moreover, there existed a certain degree of non-uniformity in the microstructures and mechanical properties along the thickness direction of welding seam, and the samples in the upper area of welding seam showed better comprehensive properties than the lower ones. When welded at a moderate speed as 1.0 m/min, the welding seams exhibited the best mechanical properties and the least difference across the thickness direction of the welding seam. This is because the moderate welding speed resulted in the most beneficial macro- and micro-structures as well as grain boundary characteristics.

Abstract Disease modeling with isogenic Induced Pluripotent Stem Cell (iPSC)-differentiated organoids serves as a powerful technique for studying disease mechanisms. Multiplexed coculture is crucial to mitigate batch effects when studying the genetic effects of disease-causing variants in differentiated iPSCs or organoids, and demultiplexing at the single-cell level can be conveniently achieved by assessing natural genetic barcodes. Here, to enable cost-efficient time-series experimental designs via multiplexed bulk and single-cell RNA-seq of hybrids, we introduce a computational method in our Vireo Suite, Vireo-bulk, to effectively deconvolve pooled bulk RNA-seq data by genotype reference, and thereby quantify donor abundance over the course of differentiation and identify differentially expressed genes among donors. Furthermore, with multiplexed scRNA-seq and bulk RNA-seq, we demonstrate the usefulness and necessity of a pooled design to reveal donor iPSC line heterogeneity during macrophage cell differentiation and to model rare WT1 mutation-driven kidney disease with chimeric organoids. Our work provides an experimental and analytic pipeline for dissecting disease mechanisms with chimeric organoids.

Abstract Background Insulin resistance (IR) plays an important role in the pathophysiology of cardiovascular disease. Recent studies have shown that diabetes mellitus and impaired lipid metabolism are associated with the severity and prognosis of idiopathic pulmonary arterial hypertension (IPAH). However, the relationship between IR and pulmonary hypertension is poorly understood. This study explored the association between four IR indices and IPAH using data from a multicenter cohort. Methods A total of 602 consecutive participants with IPAH were included in this study between January 2015 and December 2022. The metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, and triglyceride-glucose-body mass index (TyG-BMI) were used to quantify IR levels in patients with IPAH. The correlation between non-insulin-based IR indices and long-term adverse outcomes was determined using multivariate Cox regression models and restricted cubic splines. Results During a mean of 3.6 years’ follow-up, 214 participants experienced all-cause death or worsening condition. Compared with in low to intermediate-low risk patients, the TG/HDL-C ratio (2.9 ± 1.7 vs. 3.3 ± 2.1, P = 0.003) and METS-IR (34.5 ± 6.7 vs. 36.4 ± 7.5, P

Abstract Background Glomerular lesions are the main injuries of diabetic nephropathy (DN) and are used as a crucial index for pathologic classification. Manual quantification of these morphologic features currently used is semi-quantitative and time-consuming. Automatically quantifying glomerular morphologic features is urgently needed. Methods A series of convolutional neural networks (CNN) were designed to identify and classify glomerular morphologic features in DN patients. Associations of these digital features with pathologic classification and prognosis were further analyzed. Results Our CNN-based model achieved a 0.928 F1-score for global glomerulosclerosis and 0.953 F1-score for Kimmelstiel-Wilson lesion, further obtained a dice of 0.870 for the mesangial area and F1-score beyond 0.839 for three glomerular intrinsic cells. As the pathologic classes increased, mesangial cell numbers and mesangial area increased, and podocyte numbers decreased (p for all

Abstract Background Patients with pulmonary arterial hypertension (PAH) exhibit a distinct gut microbiota profile; however, the causal association between gut microbiota, associated metabolites, and PAH remains elusive. We aimed to investigate this causal association and to explore whether dietary patterns play a role in its regulation. Methods Summary statistics of gut microbiota, associated metabolites, diet, and PAH were obtained from genome-wide association studies. The inverse variance weighted method was primarily used to measure the causal effect, with sensitivity analyses using the weighted median, weighted mode, simple mode, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger methods. A reverse Mendelian randomisation analysis was also performed. Results Alistipes (odds ratio [OR] = 2.269, 95% confidence interval [CI] 1.100–4.679, P = 0.027) and Victivallis (OR = 1.558, 95% CI 1.019–2.380, P = 0.040) were associated with an increased risk of PAH, while Coprobacter (OR = 0.585, 95% CI 0.358–0.956, P = 0.032), Erysipelotrichaceae (UCG003) (OR = 0.494, 95% CI 0.245–0.996, P = 0.049), Lachnospiraceae (UCG008) (OR = 0.596, 95% CI 0.367–0.968, P = 0.036), and Ruminococcaceae (UCG005) (OR = 0.472, 95% CI 0.231–0.962, P = 0.039) protected against PAH. No associations were observed between PAH and gut microbiota-derived metabolites (trimethylamine N-oxide [TMAO] and its precursors betaine, carnitine, and choline), short-chain fatty acids (SCFAs), or diet. Although inverse variance-weighted analysis demonstrated that elevated choline levels were correlated with an increased risk of PAH, the results were not consistent with the sensitivity analysis. Therefore, the association was considered insignificant. Reverse Mendelian randomisation analysis demonstrated that PAH had no causal impact on gut microbiota-derived metabolites but could contribute to increased the levels of Butyricicoccus and Holdemania, while decreasing the levels of Clostridium innocuum, Defluviitaleaceae UCG011, Eisenbergiella, and Ruminiclostridium 5. Conclusions Gut microbiota were discovered suggestive evidence of the impacts of genetically predicted abundancy of certain microbial genera on PAH. Results of our study point that the production of SCFAs or TMAO does not mediate this association, which remains to be explained mechanistically.

Abstract Aims Despite refinements in balloon pulmonary angioplasty (BPA), total occlusion remains a challenge in chronic thromboembolic pulmonary hypertension (CTEPH). Owing to their low success and high complication rates, most interventional cardiologists are reluctant to address total occlusion, and there is a paucity of literature on BPA performance in total occlusion. We aimed to classify total occlusion according to morphology and present an illustrative approach for devising a tailored treatment strategy for each distinct type of total occlusion. Methods and results All patients diagnosed with CTEPH who underwent BPA between May 2018 and May 2022 at Fuwai Hospital in Beijing, China, were included retrospectively. A total of 204 patients with CTEPH who underwent BPA were included in this study. Among these, 38 occluded lesions were addressed in 33 patients. Based on the morphology, we categorized the lesions into three groups: pointed‐head, round‐head, and orifice occlusions. Pointed‐head occlusion could be successfully addressed using soft‐tip wire, round‐head occlusion warranted hard‐tip wire and stronger backup, and orifice occlusion warranted the strongest backup force. The success rates for each group were as follows: pointed‐head (95.45%), round‐head (46.15%), and orifice occlusion (33.33%), with orifice occlusion having the highest complication rate (50%). The classification of occlusion was associated with BPA success (round‐head occlusion vs. pointed‐head occlusion, OR 24.500, 95% CI 2.498–240.318, P = 0.006; orifice occlusion vs. pointed‐head occlusion, OR 42.000, 95% CI 3.034–581.434, P = 0.005). Conclusions Occlusion morphology has a significant impact on BPA success and complication rates. A treatment strategy tailored to each specific occlusive lesion, as outlined in the present study, has the potential to serve as a valuable guide for clinical practitioners.

To understand the seasonal variations in shellfish community structure, the composition and diversity of shellfish in the intertidal zone of the Changshan Archipelago, China, were investigated. We investigated the composition and diversity of shellfish species in the intertidal zone (including NCD1, NCD2, BCD1, BCD2, TJD1, TJD2, DQD1, DQD2, NHD1, and NHD2) of five representative islands and 10 survey stations in the Changshan Archipelago during the low tide period in July and October 2021 and February and May 2022, and the water quality parameters of point water and interstitial water were analyzed. The results showed that the bottom material of the Changshan Archipelago was generally rock or gravel and the salinity fluctuated with the seasons. The salinity was high in summer and fall while low in spring and winter, with an average of 30.92±0.84. Compared with spring, summer, and fall, the temperature changed significantly in winter, with an average of (4.51±0.32) ℃ and the highest temperature being 23.48 ℃ during spring, summer, and fall. In general, the dissolved oxygen in the main islands of Changshan Archipelago (North and South Changshan Islands) was relatively low, with an average of (8.59±0.38) mg/L, while that in Tuoji Island, Daqin Island, and Nanhuangcheng Island was relatively high, with an average of (9.95±0.51) mg/L. A total of 12 species of shellfish were collected in this survey, including Crassostrea sp., Monodonta labio Linnaeus, Littorina brevicula, Mytilus galloprovincialis, Patelloida pygmaea, Chlorostoma rustica, Reishia clavigera, Thais luteostoma, Ocinebrellus inornata, Cellana toreuma, Ruditapes philippinarum, and Rapana venosa. The number of shellfish species in each season was the highest in spring, with an average of eight species, followed by in fall, with an average of six species. Winter had the least number of shellfish species collected, with an average of four species. In addition, the North and South Changshan Islands presented the most shellfish species at eight and nine species, respectively. The number of shellfish collected in DQD was the least (six species). There were differences in shellfish density at different survey sites, among which DQD2 had the highest density, with an average density of 41.26 ind./m2. The lowest density was in NCD2, and the average density was 13.71 ind./m2. In the same season, the shellfish density at different survey sites was different, the proportion of dominant species at different survey sites was also different. In spring, the density of Crassostrea sp., Cellana toreuma, and Chlorostoma rustica was high, while in summer, the density of Crassostrea sp., Mytilus galloprovincialis, Littorina brevicula, and Cellana toreuma was high. In fall, the density of Crassostrea sp., Littorina brevicula, and Mytilus galloprovincialis was the highest, while in winter, the density of Crassostrea sp., Patelloida pygmaea, and Cellana toreuma was the highest. The species diversity (H´) of shellfish in each tidal area of the survey site is shown as middle tidal zone (1.44) > low tidal zone (1.40) > high tidal zone (0.44). Overall, the average shellfish species diversity in the 10 survey sites was spring (1.26) > winter (1.21) > fall (1.11) > summer (0.95). The average evenness index of species (J´) in the 10 survey stations was 0.55, among which the evenness index of DQD2, NCD2, NHD2, and TJD1 shellfish was 0.67, 0.64, 0.64, and 0.55, respectively. The evenness index of shellfish in each tidal area of the survey site was in order of middle tidal zone (0.67) > low tidal zone (0.59) > high tidal zone (0.29). The seasonal change was not obvious. The average shellfish abundance at the survey site was 0.533, including 0.82, 0.68, 0.60, and 0.53 shellfish abundance at NCD2, NHD2, BCD2, and NCD1, respectively. The abundance index of shellfish in each tidal area of the survey site was in order of middle tidal zone (0.56) > low tidal zone (0.52) > high tidal zone (0.17). Overall, the average shellfish abundance in the 10 survey sites was spring (0.681) > fall (0.573) > summer (0.458) > winter (0.418). Seasons (temperatures) have the most obvious impact on the diversity and abundance of intertidal shellfish resources. Anthropogenic activities, such as aquaculture and tourism, also affect the distribution and quantity of shellfish species. The results of this study not only enrich the data of intertidal shellfish resources on islands in China but also provide basic information and reference for biodiversity and environmental protection of intertidal shellfish on the Changshan Islands.

BackgroundMigraine patients have an increased long-term risk of cardio and cerebrovascular events. However, whether these patients are more susceptible to white matter lesions (WMLs) remains debated. To explore this question, our study assessed the proportion of RLS in migraine patients and explored the association between right-to-left shunt (RLS) and WMLs.MethodsIn this study, we included 998 migraine patients. Contrast transcranial doppler (c-TCD) was used to diagnose RLS and assess the extent of the shunt in RLS patients. Of the 998 patients, 505 underwent cranial magnetic resonance imaging (MRI) assessments. WMLs were classified into periventricular white matter lesions (pvWMLs) and deep white matter lesions (dWMLs).ResultsAmong the 998 migraine patients, 946 had migraine without aura (MO; mean age 36.68 ± 10.46 years; 80.5% female), and 52 had migraine with aura (MA; mean age 29.85 ± 8.59 years; 71.2% female). Compared with MO patients, MA patients had an earlier onset age (23.1 ± 7.97 vs. 28.44 ± 10.38 years, p

Glycogen, a highly branched polysaccharide of essential energy and carbon resource, is an important flavor quality trait of oysters, and its content is closely linked to the reproductive cycle of these mollusks. However, there is a significant lack of research on the regulatory mechanisms governing glycogen in oysters. Here, we investigated the variations in glycogen levels during the reproductive cycle of Jinjiang oyster Crassostrea (Magallana) ariakensis. It revealed that glycogen content was highest during the formative stage and lowest during the mature stage in gonadal tissues. Subsequently, transcriptome and metabolome analyses were conducted, revealing 3016 differentially expressed genes (DEGs) and 162 differentially accumulated metabolites (DAMs). Comprehensive analysis indicated that glycogenesis, glycogenolysis, glycolysis, and tricarboxylic acid (TCA) cycle played crucial roles in energy supply during the formative stage. Gluconeogenesis was more important during the mature stage as it facilitated glycogen storage for reproduction preparation. These findings provide valuable insights into the mechanisms underlying gonad development-related glycogen metabolism and offer a theoretical foundation for enhancing oyster flavor.

Abstract Wilms tumor‐1(WT1) is a crucial transcription factor that regulates podocyte development. However, the epigenomic mechanism underlying the function of WT1 during podocyte development has yet to be fully elucidated. Here, single‐cell chromatin accessibility and gene expression maps of foetal kidneys and kidney organoids are generated. Functional implications of WT1‐targeted genes, which are crucial for the development of podocytes and the maintenance of their structure, including BMPER/PAX2/MAGI2 that regulates WNT signaling pathway, MYH9 that maintains actin filament organization and NPHS1 that modulates cell junction assembly are identified. To further illustrate the functional importance of WT1‐mediated transcriptional regulation during podocyte development, cultured and implanted patient‐derived kidney organoids derived from the Induced Pluripotent Stem Cell (iPSCs) of a patient with a heterozygous missense mutation in WT1 are generated. Results from single‐cell RNA sequencing (scRNA‐seq) and functional assays confirm that the WT1 mutation leads to delays in podocyte development and causes damage to cell structures, due to its failure to activate the targeting genes MAGI2, MYH9, and NPHS1. Notably, correcting the mutation in the patient iPSCs using CRISPR‐Cas9 gene editing rescues the podocyte phenotype. Collectively, this work elucidates the WT1‐related epigenomic landscape with respect to human podocyte development and identifies the disease‐causing role of a WT1 mutation.

Sheep body size can directly reflect the growth rates and fattening rates of sheep and is also an important index for measuring the growth performance of meat sheep.Inner Mongolia Cashmere Goat is a local excellent breed of cashmere and meat dual-purpose, which is a typical heterogeneous indumentum. The hair follicles cycle through periods of vigorous growth (anagen), a regression caused by apoptosis (catagen), and relative rest (telogen). At present, it is not clear which genes affect the cycle transformation of hair follicles and unclear how proteins impact the creation and expansion of hair follicles.we using multi-omics joint analysis methodologies to investigated the possible pathways of transformation and apoptosis in goat hair follicles. The results showed that 917,1,187, and 716 proteins were specifically expressed in anagen, catagen andtelogen. The result of gene ontology (GO) annotation showed that differentially expressed proteins (DEPs) are in different growth cycle periods, and enriched GO items are mostly related to the transformation of cells and proteins. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment result indicated that the apoptosis process has a great impact on hair follicle’s growth cycle. The results of the protein interaction network of differential proteins showed that the ribosomal protein family (RPL4, RPL8, RPS16, RPS18, RPS2, RPS27A, RPS3) was the core protein in the network. The results of combined transcriptome and proteomics analysis showed that there were 16,34, and 26 overlapped DEGs and DEPs in the comparison of anagen VS catagen, catagen VS telogen and anagen VS telogen, of which API5 plays an important role in regulating protein and gene expression levels. We focused on API5 and Ribosomal protein and found that API5 affected the apoptosis process of hair follicles, and ribosomal protein was highly expressed in the resting stage of hair follicles. They are both useful as molecular marker candidate genes to study hair follicle growth and apoptosis,and they both have an essential function in the cycle transition process of hair follicles. The results of this study may provide a theoretical basis for further research on the growth and development of hair follicles in Inner Mongolian Cashmere goats.

Cracks of varying lengths may occur in galleries throughout dam construction, operation, and management processes. This study investigates the influence of age and crack length on the fracture parameters of gallery concrete, which is crucial for understanding the mechanisms and risks associated with gallery cracking and for developing appropriate treatment measures. Wedge-splitting tests were performed on gallery concrete specimens with varying crack lengths and at different ages. It was found that the fracture parameters measured at different ages all decrease with the increase of crack length. Based on the test results, size-independent material constants such as fracture toughness and the effective length of the fracture process zone were derived and modeled using an exponential function to reflect their time-varying characteristics. A fracture model was proposed and validated, which can accurately predict the fracture behavior of gallery concrete across varying ages and crack lengths, and is applicable in practical dam gallery crack analysis for assessing crack stability and evaluating the effectiveness of treatment measures.

Abstract We aimed to identify the key potential insulin resistance (IR)-related genes and investigate their correlation with immune cell infiltration in type 2 diabetes (T2D). The GSE78721 dataset (68 diabetic patients and 62 controls) was downloaded from the Gene Expression Omnibus database and utilized for single-sample gene set enrichment analysis. IR-related genes were obtained from the Comparative Toxicology Genetics Database, and the final IR-differentially expressed genes (DEGs) were screened by intersecting with the DEGs obtained from the GSE78721 datasets. Functional enrichment analysis was performed, and the networks of the target gene with microRNA, transcription factor, and drug were constructed. Hub genes were identified based on a protein–protein interaction network. Least absolute shrinkage and selection operator regression and Random Forest and Boruta analysis were combined to screen diagnostic biomarkers in T2D, which were validated using the GSE76894 (19 diabetic patients and 84 controls) and GSE9006 (12 diabetic patients and 24 controls) datasets. Quantitative real-time polymerase chain reaction was performed to validate the biomarker expression in IR mice and control mice. In addition, infiltration of immune cells in T2D and their correlation with the identified markers were computed using CIBERSORT. We identified differential immune gene set regulatory T-cells in the GSE78721 dataset, and T2D samples were assigned into three clusters based on immune infiltration. A total of 2094 IR-DEGs were primarily enriched in response to endoplasmic reticulum stress. Importantly, HDAC9 and ARRDC4 were identified as markers of T2D and associated with different levels of immune cell infiltration. HDAC9 mRNA level were higher in the IR mice than in control mice, while ARRDC4 showed the opposite trend. In summary, we discovered potential vital biomarkers that contribute to immune cell infiltration associated with IR, which offers a new sight of immunotherapy for T2D.

Abstract Background Coronavirus disease 2019 (COVID-19) is an evolving global pandemic, and nanobodies, as well as other single-domain antibodies (sdAbs), have been recognized as a potential diagnostic and therapeutic tool for infectious diseases. High-throughput screening techniques such as phage display have been developed as an alternative to in vivo immunization for the discovery of antibody-like target-specific binders. Methods We designed and constructed a highly diverse synthetic phage library sdAb-U (single-domain Antibody - Universal library ) based on a human framework. The SARS-CoV-2 receptor-binding domain (RBD) was expressed and purified. The universal library sdAb-U was panned against the RBD protein target for two rounds, followed by monoclonal phage ELISA (enzyme-linked immunosorbent assay) to identify RBD-specific binders (the first stage). High-affinity binders were sequenced and the obtained CDR1 and CDR2 sequences were combined with fully randomized CDR3 to construct a targeted (focused) phage library sdAb-RBD, for subsequent second-stage phage panning (also two rounds) and screening. Then, sequences with high single-to-background ratios in phage ELISA were selected for expression. The binding affinities of sdAbs to RBD were measured by an ELISA-based method. In addition, we conducted competition ELISA (using ACE2 ectodomain S19-D615) and SARS-CoV-2 pseudovirus neutralization assays for the high-affinity RBD-binding sdAb39. Results Significant enrichments were observed in both the first-stage (universal library) and the second-stage (focused library) phage panning. Five RBD-specific binders were identified in the first stage with high ELISA signal-to-background ratios. In the second stage, we observed a much higher possibility of finding RBD-specific clones in phage ELISA. Among 45 selected RBD-positive sequences, we found eight sdAbs can be well expressed, and five of them show high-affinity to RBD (EC50

Abstract Background Identifying venous thromboembolism (VTE) is challenging for patients with cardiovascular diseases due to similar clinical presentation. Most hospital-acquired VTE events are preventable, whereas the implementation of VTE prophylaxis in clinical practice is far from sufficient. There is a lack of hospital-acquired VTE prediction models tailored specifically designed for patients with cardiovascular diseases. We aimed to develop a nomogram predicting hospital-acquired VTE specifically for patients with cardiovascular diseases. Material and methods Consecutive patients with cardiovascular diseases admitted to internal medicine of Fuwai hospital between September 2020 and August 2021 were included. Univariable and multivariable logistic regression were applied to identify risk factors of hospital-acquired VTE. A nomogram was constructed according to multivariable logistic regression, and internally validated by bootstrapping. Results A total of 27,235 patients were included. During a median hospitalization of four days, 154 (0.57%) patients developed hospital-acquired VTE. Multivariable logistic regression identified that female sex, age, infection, pulmonary hypertension, obstructive sleep apnea, acute coronary syndrome, cardiomyopathy, heart failure, immobility, central venous catheter, intra-aortic balloon pump and anticoagulation were independently associated with hospital-acquired VTE. The nomogram was constructed with high accuracy in both the training set and validation (concordance index 0.865 in the training set, and 0.864 in validation), which was further confirmed in calibration. Compared to Padua model, the Fuwai model demonstrated significantly better discrimination ability (area under curve 0.865 vs. 0.786, net reclassification index 0.052, 95% confidence interval 0.012–0.091, P = 0.009; integrated discrimination index 0.020, 95% confidence interval 0.001–0.039, P = 0.051). Conclusion The incidence of hospital-acquired VTE in patients with cardiovascular diseases is relatively low. The nomogram exhibits high accuracy in predicting hospital-acquired VTE in patients with cardiovascular diseases.

Abstract Background An increased acetylcholine (ACh) level in the right ventricle tissue of pulmonary hypertension (PH) was revealed, which indicated the important role of ACh in disease pathogenesis. However, the relationship between plasma ACh levels and disease conditions and patients’ prognosis has not been investigated. We aimed to explore the association between plasma ACh levels and the prognosis of patients with PH. We also discussed the feasibility of plasma ACh as a biomarker, which may contribute to the management of PH patients in the future. Methods Patients with confirmed PH in Fuwai Hospital from April 2019 to August 2020 were enrolled. The primary clinical outcome in this study was defined as a composite outcome, including death/lung transplantation, heart failure, and worsening of symptoms. Fasting plasma was collected to detect the ACh levels. The association between ACh levels and patients’ prognosis was explored. Results Finally, four hundred and eight patients with PH were enrolled and followed for a mean period of 2.5 years. Patients in the high ACh group had worse World Health Organization Functional Class (WHO-FC), lower 6-minute walk distance (6 MWD), and higher N-terminal pro-brain natriuretic peptide (NT-proBNP). Notably, echocardiographic and hemodynamic parameters in the high metabolite group also suggested a worse disease condition compared with the low ACh group. After adjusting for confounders, compared with low ACh patients, those with high metabolite levels still have worse prognoses characterized as elevated risk of mortality, heart failure, and symptoms worsening. Conclusion High circulating ACh levels were associated with severe PH conditions and poor prognosis, which might serve as a potential biomarker in PH.

Abstract Background Clinical characteristics of patients with pulmonary thromboembolism have been described in previous studies. Although very old patients with pulmonary thromboembolism are a special group based on comorbidities and age, they do not receive special attention. Objective This study aims to explore the clinical characteristics and mortality predictors among very old patients with pulmonary thromboembolism in a relatively large population. Design and participants The study included a total of 7438 patients from a national, multicenter, registry study, the China pUlmonary thromboembolism REgistry Study (CURES). Consecutive patients with acute pulmonary thromboembolism were enrolled and were divided into three groups. Comparisons were performed between these three groups in terms of clinical characteristics, comorbidities and in-hospital prognosis. Mortality predictors were analyzed in very old patients with pulmonary embolism. Key results In 7,438 patients with acute pulmonary thromboembolism, 609 patients aged equal to or greater than 80 years (male 354 (58.1%)). There were 2743 patients aged between 65 and 79 years (male 1313 (48%)) and 4095 patients aged younger than 65 years (male 2272 (55.5%)). Patients with advanced age had significantly more comorbidities and worse condition, however, some predisposing factors were more obvious in younger patients with pulmonary thromboembolism. PaO2

Plutonium-238 has always been considered as the one of the promising radioisotopes for space nuclear power supply, which has long half-life, low radiation protection level, high power density, and stable fuel form at high temperatures. The industrial-scale production of 238Pu mainly depends on irradiating solid 237NpO2 target in high flux reactors, however the production process faces problems such as large fission loss and high requirements for product quality control. In this paper, a conceptual design study of producing 238Pu in a multi-purpose high flux reactor was evaluated and analyzed, which includes a sensitivity analysis on 238Pu production and a further study on the irradiation scheme. It demonstrated that the target structure and its location in the reactor, as well as the operation scheme has an impact on 238Pu amount and product quality. Furthermore, the production efficiency could be improved by optimizing target material concentration, target locations in the core and reflector. This work provides technical support for irradiation production of 238Pu in high flux reactors.

This study aimed to investigate the impact of building planes on the microstructure and corrosion behaviors of 316L stainless steel (SS) manufactured using selective laser melting (SLM) when subjected to a 0.1 M HCl solution. The investigation of material corrosion behavior involved the utilization of a wide array of surface characterization techniques, as well as various electrochemical measurements. The findings were subjected to a comparison with those obtained from a commercially rolled 316L SS (R 316L SS). The analysis revealed that the XZ and YZ planes displayed a distinctive fish scale melt pool structure, while the XY plane exhibited a columnar melt pool structure. The densities of the low-angle grain boundaries for different building planes were observed as YZ

As the core component of China Fusion Engineering Test Reactor (CFETR), the forming and manufacturing of the first wall faces severe challenges due to the constraints of materials, service environment and geometric structure. The microstructure and mechanical properties of welded joints obtained by rolled and laser selective melted (SLMed) reduced activation ferritic/martensitic (RAFM) steel were investigated in depth. The microstructure analysis results showed that the weld metal (WM) was composed of coarse lath martensite and δ-ferrite, while the microstructure were mainly coarse grains in heat affected zone (HAZ) which was easy to break. The average grains size of SLMed RAFM steel (S-RAFMs) was smaller than that of rolled RAFM steel (R-RAFMs), since the rapid melting and solidification of laser in the additive manufacturing process prevented grains to grow. The microstructure of R-RAFMs joint was relatively more uniform and there was no obvious texture and preferred orientation, while the WM of S-RAFMs joint had a weak cubic texture. The results of mechanical properties showed that the S-RAFMs joints exhibited higher strength (UTS = 697.46 MPa) and the R-RAFMs joints exhibited better plasticity (EL = 13.49 %) under the same tensile conditions. The tensile and impact fracture morphologies showed that the fracture mechanism of two joints was ductile-brittle mixed fracture, and the dimples of R-RAFMs joints were finer and denser. It was clearly observed that the hardness of WM (∼390–430 HV0.3) was higher than that of the base metal (BM) (∼190–230 HV0.3) from the hardness distributions along the width directions. The average hardness of BM in R-RAFMs joint (227 HV0.3) was lower than S-RAFMs joint (197.3 HV0.3), which was mainly related to the fine grain strengthening effect during SLM forming. The above results may provide theoretical guidance for the high-performance manufacturing of the first wall and promote the application of SLM and EBW technology in the field of nuclear fusion.

In previous studies, the implementation of vegetation structure information remains underutilized during the assessment of burn severity. A PolSAR-based burn severity assessment model was proposed by incorporating polarimetric decomposition features. Based on coherence matrix, three polarimetric decomposition features (i.e. Entropy, Anisotropy, and Alpha) which might be related with some field variables of burn severity (e.g. percent foliage altered, percent change in cover, percent canopy mortality, and percent tree mortality) were extracted. Then, a sensitivity analysis of 20 PolSAR features was performed and a principal component analysis (PCA) was applied. Finally, the combination of polarimetric decomposition features and new PCA vectors were used as inputs and CBI values as outputs of random forest algorithm to assess burn severity. The Jinyun Mountain in the Chongqing municipality of China was used as study area and the C-band of dual-polarization SAR data acquired from Sentinel-1 satellite were used as remotely sensed data. The sensitivity analysis of PolSAR features showed that H, A, and α features exhibited higher correlations with CBI values, compared to SAR indices. For proposed model, the R was 0.60 and the RMSE was 0.55. This study offered a new research perspective for future investigations on PolSAR-based burn severity assessment of wildfires.

Yesso scallop Patinopecten yessoensis is an economically and ecologically important cold-water bivalve molluscs. Elucidating the molecular mechanism regulating its early larval development holds great significance in aquaculture. This study performed comparative transcriptomic analysis across nine developmental stages from fertilized eggs to spats. A variety of differentially expressed genes (DEGs) were identified to be potentially involved in larval development, including cell proliferation (cyclins, CDKs, BMPs, TGF-β), immunity (TLR7, CTLs, cathepsins, SOD, GSTs), larval settlement and metamorphosis (MHC, MELC, paramyosin, DβH, GABA receptor), shell formation (iMSP5, MSP1, CHS1, CHI3, CAM, CAML5) as well as energy metabolism (glycolysis, TCA cycle and oxidative phosphorylation components). Additionally, weighted gene co-expression network analysis (WGCNA) identified the key indianred4 module, which may play vital roles in body axis formation, neurogenesis and myogenesis in scallop larvae. An integrative framework was established delineating molecular drivers of embryogenesis, larval growth, immune defense, metamorphosis, shell production and bioenergetics throughout larval development in scallops. These findings will help understand the molecular strategies governing larval developmental process, yielding great insights to inform ecological conservation and aquaculture practices.

Cellulose has advantages of easy availability, low price, renewability and biodegradability, making it a very promising substitute for fossil-based materials. A safe composite cellulose membrane for quasi-solid-state lithium ion batteries has been developed by coating cellulose separators with poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) and lithium aluminum titanium phosphate (LATP). This membrane exhibits excellent electrochemical performance, with an ionic conductivity as high as 2.1 mS cm−1, and a lithium-ion transference number of 0.57. The membrane shows good electrolyte wetting properties, with porosity and liquid electrolyte uptake of 47.2 % and 401.7 %, respectively. It has good thermal stability and can maintain its dimensional stability even at 200 ℃. The capacity retention of the quasi-solid-state LiFePO4/Li battery assembled with this membrane after 200 cycles at 0.2 C is about 86.7 %. The quasi-solid-state battery has good thermal stability and is not prone to thermal runaway.

The poly (ethylene oxide) (PEO) solid polymer electrolytes suffer from narrow electrochemical stability window and cannot match high voltage lithium cobalt oxide (LCO) cathode. Herein, an ultrathin Al2O3 nanolayer was uniformly deposited on the surface of LCO via powder atomic layer deposition (PALD) to realize poly (ethylene oxide) polymer electrolyte cycling stability. The PEO solid polymer electrolyte contains 20 % (w/w) lithium difluoro(oxalate)borate (LiDFOB) and 7.5 % (w/w) lithium titanium aluminum phosphate (LATP) with cellulose nonwoven as a support substrate. The electrolyte exhibitsionic conductivity of 1.2×10−4 S cm−1, an electrochemical stability window of 4.5 V (vs. Li+/Li) and lithium-ion transference number of 0.38. Al2O3@LCO/PEO-LiDFOB20%-LATP7.5%/Li cell at high cut-off 4.5 V delivered better initial discharge specific capacity of 178.5 mAh g−1 and achieved a capacity retention ratio of 81.6 % after 200 cycles under 0.1 C at 50 °C. Further analysis showed that Al2O3 layer served as stable a protective layer to suppress the generation of strong oxidative Co4+ and O– species and separate from the PEO solid polymer electrolyte, inhibiting the side reactions at the cathode-side interface. Therefore, architecting precise and ultrathin protective nanolayer interface on high voltage LCO cathode via PALD is conducive to cycling performance of solid polymer electrolyte.

Abstract Neoantigen peptides hold great potential as vaccine candidates for tumor immunotherapy. However, due to the limitation of antigen cellular uptake and cross‐presentation, the progress with neoantigen peptide‐based vaccines has obviously lagged in clinical trials. Here, a stapling peptide‐based nano‐vaccine is developed, comprising a self‐assembly nanoparticle driven by the nucleic acid adjuvant‐antigen conjugate. This nano‐vaccine stimulates a strong tumor‐specific T cell response by activating antigen presentation and toll‐like receptor signaling pathways. By markedly improving the efficiency of antigen/adjuvant co‐delivery to the draining lymph nodes, the nano‐vaccine leads to 100% tumor prevention for up to 11 months and without tumor recurrence, heralding the generation of long‐term anti‐tumor memory. Moreover, the injection of nano‐vaccine with signal neoantigen eliminates the established MC‐38 tumor (a cell line of murine carcinoma of the colon without exogenous OVA protein expression) in 40% of the mice by inducing potent cytotoxic T lymphocyte infiltration in the tumor microenvironment without substantial systemic toxicity. These findings represent that stapling peptide‐based nano‐vaccine may serve as a facile, general, and safe strategy to stimulate a strong anti‐tumor immune response for the neoantigen peptide‐based personalized tumor immunotherapy.

Abstract Migrasomes represent a recently uncovered category of extracellular microvesicles, spanning a diameter range of 500 to 3000 nm. They are emitted by migrating cells and harbour a diverse array of RNAs and proteins. Migrasomes can be readily identified in bodily fluids like serum and urine, rendering them a valuable non‐invasive source for disease diagnosis through liquid biopsy. In this investigation, we introduce a streamlined and effective approach for the capture and quantitative assessment of migrasomes, employing wheat germ agglutinin (WGA)‐coated magnetic beads and flow cytometry (referred to as WBFC). Subsequently, we examined the levels of migrasomes in the urine of kidney disease (KD) patients with podocyte injury and healthy volunteers using WBFC. The outcomes unveiled a substantial increase in urinary podocyte‐derived migrasome concentrations among individuals with KD with podocyte injury compared to the healthy counterparts. Notably, the urinary podocyte‐derived migrasomes were found to express an abundant quantity of phospholipase A2 receptor (PLA2R) proteins. The presence of PLA2R proteins in these migrasomes holds promise for serving as a natural antigen for the quantification of autoantibodies against PLA2R in the serum of patients afflicted by membranous nephropathy. Consequently, our study not only pioneers a novel technique for the isolation and quantification of migrasomes but also underscores the potential of urinary migrasomes as a promising biomarker for the early diagnosis of KD with podocyte injury.

Summary: Signal-regulatory protein alpha (SIRPα) has recently been found to be highly expressed in podocytes and is essential for maintaining podocyte function. However, its immunoregulatory function in podocytes remains elusive. Here, we report that SIRPα controls podocyte antigen presentation in specific T cell activation via inhibiting spleen tyrosine kinase (Syk) phosphorylation. First, podocyte SIRPα under lupus nephritis (LN) conditions is strongly downregulated. Second, podocyte-specific deletion of SIRPα exacerbates renal disease progression in lupus-prone mice, as evidenced by an increase in T cell infiltration. Third, SIRPα deletion or knockdown enhances podocyte antigen presentation, which activates specific T cells, via enhancing Syk phosphorylation. Supporting this, Syk inhibitor GS-9973 prevents podocyte antigen presentation, resulting in a decrease of T cell activation and mitigation of renal disease caused by SIRPα knockdown or deletion. Our findings reveal an immunoregulatory role of SIRPα loss in promoting podocyte antigen presentation to activate specific T cell immune responses in LN.

Sheep body size can directly reflect the growth rates and fattening rates of sheep and is also an important index for measuring the growth performance of meat sheep. In this study, high-resolution resequencing data from four sheep breeds (Dorper sheep, Suffolk sheep, Ouessant sheep, and Shetland sheep) were analyzed. The nonsynonymous single nucleotide polymorphisms of three candidate genes (KIAA1217, SNTA1, and LTBP1) were also genotyped in 642 healthy Ujumqin sheep using MALDI-TOFMS and the genotyping results were associated with growth traits. The results showed that different genotypes of the KIAA1217 g.24429511T>C locus had significant effects on the chest circumferences of Ujumqin sheep. The SNTA1 g.62222626C>A locus had different effects on the chest depths, shoulder widths and rump widths of Ujumqin sheep. This study showed that these two sites can be used for marker-assisted selection, which will be beneficial for future precision molecular breeding.

The manila clam Ruditapes philippinarum has become an important bivalve species in worldwide aquaculture due to its delicious taste and high commercial value. With the rapid expansion of clam farming, there is an urgent need to obtain genetic improvement by selective breeding, such as family-based selection of improved varieties. In this study, 10 microsatellite loci were selected to establish four multiplex PCR groups using four different fluorescences (FAM, ROX, HEX, TAM). The accuracy of these loci was verified by the 100% success rate of parentage assignment in a full-sib family. Parentage assignment was carried out in the mixed-mating parents and their offspring with unknown pedigree information. The genotyping of ten microsatellite loci generated 90 alleles, having the observed heterozygosity (Ho) ranging from 0.333 to 0.729. The expected heterozygosity (He) varied from 0.358 to 0.794. The PIC ranged from 0.342 to 0.763, with a mean value of 0.620. The theoretical combined parentage exclusion (cEP) power for all ten microsatellites was 97% with known genotypes of one parent (P1) and 99% for given the genotypes of both parents (P2). The actual successful assignment rate reached 98% by using all four sets of multiplex microsatellites, serving as the effective method for parentage assignment in the clams. The development and application of multiplex microsatellite genotyping methods provide a cost-effective method for pedigree reconstruction, population genetics and selective breeding of the commercially important clams.

IntroductionCircadian syndrome (CircS) is proposed as a novel risk cluster based on reduced sleep duration, abdominal obesity, depression, hypertension, dyslipidemia and hyperglycemia. However, the association between CircS and chronic kidney disease (CKD) remains unclear. To investigate the cross-sectional and longitudinal association between CircS and CKD, this study was performed.MethodsA national prospective cohort (China Health and Retirement Longitudinal Study, CHARLS) was used in this study. To define CKD, the estimated glomerular filtration rate (eGFR) was calculated based on the 2012 CKD-EPI creatinine-cystatin C equation. Participants with eGFR

Abstract Objective To evaluate the feasibility of an internet-facilitated community model for cervical cancer screening using self-collected HPV testing as primary screening. Method A population-based cervical cancer screening program was conducted in the suburb of Shenzhen, China, from September 2014 to July 2017. Women with 25–60 years of age and no pregnancy were eligible for participation. Participants could register for screening by logging in a website by themselves or with the aids of local community workers. A unique barcode was issued to each applicant upon successful registration. After registration, women could get sampling kits from community screening site/study clinic, collect vaginal samples privately or in group, and provide their sample for Hr-HPV tests on Cobas4800 and SeqHPV assays. Testing reports were checkable through personal account for all participant and phone calls were given to all women positive of Hr-HPV. Participants positive of both or either the 2 assays were identified as the positives. The positives could return the study clinic for triage or search medical care in other clinics. Colposcopy directed or ramdom biopsies were performed on all positives who returned to the study clinics. Results A total of 10,792 community women registered for screening, among whom, 10,010 provided their vaginal samples for tests. 99.5% of the participants were confirmed to have correct personal identifiable information and samples, and 98.9% of them got HPV testing results from both or either assays. No adverse event was reported. Conclusion When self-collected HPV testing is used as the primary testing, the internet-based data platform facilitates the screening in registration, data collection, and data tracking, and increases the screening coverage. Internet-facilitated community model is promising to cervical cancer control and applicable in regions with variety of resources.

Shell morphological traits are important quantitative traits in shellfish. Shell morphology is usually affected by many factors, such as the ecological environment and shellfish genetics. It is considered the results of comprehensive actions of natural selection, micro-evolution, and heredity. Measuring shell morphological traits aids our understanding of the current situation of germplasm resources among shellfish species or intraspecific populations and also provides important breeding traits for shellfish breeding programs. For most shellfish, quality traits (eg. live weight and soft body weight) are considered the important breeding traits, but there are practical issues in using these traits, such as the inability or difficulty in measuring them in vivo. It is well known that shellfish quality traits are closely related to shell morphological traits. However, a simple correlation analysis between quality and morphological traits cannot adequately explain all the intrinsic links between these traits. In this study, Manila clams (Ruditapes philippinarum) were collected from nine geographical locations along the north and south coasts of China. The shell morphology and quality characteristics were measured and analyzed for the nine different populations of clams. Furthermore, the main factors affecting the quality traits were analyzed using cluster analysis to reveal the genetic relationships among the populations. The optimal regression equations were constructed using the morphological traits with the soft weights of these populations. For all populations, shell length, shell height, shell width, and shell thickness were measured using a vernier caliper (with an accuracy of 0.01 mm) and a thickness gauge. After wiping the surface of clams with filter paper, their live weight was measured on an electronic balance (with an accuracy of 0.01 g). A scalpel was used to sample the soft body from the clams. After drying, soft body weights were calculated using the difference between live weight and shell weight. The morphological data, including mean values, standard deviation, and coefficient of variation, were calculated using SPSS 26.0. To eliminate the effects of size differences among individuals, two morphological scale parameters (shell width/shell length and shell height/shell length) were calculated to reflect the morphological characteristics of the clams. In addition, stepwise linear regression analyses were performed to obtain the correlation coefficients, direct path coefficients, correlation indexes, indirect path coefficients, and determine the coefficients using SPSS26.0 software. The correlation coefficient and multiple regression analyses of the traits were evaluated. The multiple regression equations were established for all populations. Cluster analysis was used to assess each trait using the calibrations (to calculate the ratio of each trait to shell length). The heatmap displayed the shortest distance method for the Euclidean distance between the different populations. There were significant differences in the effects of shell length, shell height, shell width, and shell thickness on live weight and soft body weight of clams. Morphological traits were significantly correlated with body weight and soft weight (P < 0.05), except for shell thickness. The results of determination coefficient revealed shell width had the greatest impact on live weights of the Putian, Jinzhou, and Chaozhou populations, with determination coefficients of 0.277, 0.232, and 0.307, respectively. The determination coefficients of soft body weights indicated that shell width played very important roles in determining soft body weights of the Putian and Chaozhou populations, with determination coefficients of 0.249 and 0.443, respectively. By calculating the total of determination coefficients, the results are consistent with the correlation index R2 for each trait. For the total determinant effects, the sum of determination coefficients for the morphological traits with soft body weights were greater than 0.850 in most populations. In contrast, the sum of determination coefficients for the morphological traits with soft body weights were less than 0.850 in Laizhou, Zhuanghe, Donggang, and Jinzhou. Based on the path analysis and the determination coefficient analysis, shell width had the greatest impact on live weights and soft body weights in most populations. The maximum values of the two morphological proportion parameters (shell width/shell length and shell height/shell length) were found in the Laizhou population (0.49 and 0.74), while the minimum proportion parameters were detected in the Dalian Donggang population (0.42 and 0.67). Among the shell morphological traits, shell thickness had the largest coefficient of variation (22.74), while shell height had the smallest coefficient of variation (9.47). By testing for statistically significant variation in the partial regression coefficient, the optimal regression equations of the morphological traits for soft body weight were constructed for all the populations. The cluster analysis revealed that different clam populations did not have a typically regional characteristic in terms of the shell morphological traits. There was an irregular north-south alternating clustering phenomenon. According to the present findings, shell thickness and morphological ratio parameters (ratio of shell height to shell length and ratio of shell width to shell length) are important indicators for evaluating the growth potential and nutritional status of clams in aquaculture. The present results provide a scientific basis for morphological discrimination and germplasm resource evaluation for geographical populations of clams and also aid breeding strategies to predict breeding traits for aquaculture breeding programs, including guidance for the selective breeding of clams.

Abstract We explore correlations harvesting by two static detectors locally interacting with vacuum massless scalar fields in the presence of an infinite perfectly reflecting boundary. We study the phenomena of mutual information harvesting and entanglement harvesting for two detector-boundary alignments, i.e., parallel-to-boundary and orthogonal-to-boundary alignments. Our results show that the presence of the boundary generally inhibits mutual information harvesting relative to that in flat spacetime without any boundaries. In contrast, the boundary may play a doubled-edged role in entanglement harvesting, i.e., inhibiting entanglement harvesting in the near zone of the boundary while assisting it in the far zone of the boundary. Moreover, there exists an optimal detector energy gap difference between two nonidentical detectors that makes such detectors advantageous in correlations harvesting as long as the interdetector separation is large enough. The value of the optimal detector energy gap difference depends on both the interdetector separation and the detector-to-boundary distance. A comparison of the correlations harvesting in two different alignments shows that although correlations harvesting share qualitatively the same properties, they also display quantitative differences in that the detectors in orthogonal-to-boundary alignment always harvest comparatively more mutual information than the parallel-to-boundary ones, while they harvest comparatively more entanglement only near the boundary.

A crack-free high-Mn TWIP steel welding joint with comparable strength and superplastic was obtained via vacuum electron beam welding (VEBW) where the microstructural evolution, mechanical behaviors and strengthening mechanism of welding joint were investigated. The results indicated that the welding joint with a typical nail-shaped welding cross-section was divided into three zones including the base metal (BM), heat-affected zone (HAZ) and fusion zone (FZ). Massive fine AlN-type precipitates with the hexagonal crystal structure were observed in welding join. The orientation relationship between the γ-austenite matrix and AlN precipitates was determined as [001]γ//[2110]AlN. In FZ, small-sized cellular grains or columnar grains with consistent growth directions were combined into large-sized columnar grains with obvious preferential orientation. Compared with the base mantal, the yield strength, ultimate strength and elongation of the VEBWed specimen were slightly reduced by 6.03%, 4.7% and 13.23%, respectively. However, the impact toughness was obviously decreased from the 87.90 J–68.97 J after the VEBW process, which was mainly attributed to the brittle AlN precipitates, inhomogeneous microstructure and back stress induced by the plastic mismatch between gradient grains. The strength contributions of different regions to overall strength including of BM, HAZ and FZ in welding joint were calculated. Here, the dislocation strengthening and precipitation strengthening were the dominant strengthening mechanisms of FZ, which was attributed to the high level of density and massive fine AlN precipitates induced by micro-elements segregations during the VEBW process.

Introduction Thirdhand smoke is an emerging threat to global public health. There is no research on young people's exposure to thirdhand smoke in China. This study aims to investigate the exposure status and beliefs of thirdhand smoke among young Chinese people and provide a reference for policy regarding thirdhand smoke. Methods Data from the 2022 Chinese Resident Psychological and Behavioral Survey were used to select young people aged 15–24 years. A total of 11781 subjects were included in this study. Demographic information, beliefs about thirdhand smoke, and exposure status to thirdhand smoke were investigated. Results Among the participants, 47.8% reported being exposed to thirdhand smoke (males: 49.1%, females: 47.0%). Young people living in urban areas (AOR=0.84, 95% CI: 0.77–0.91, p 12000 RMB (AOR=0.81, 95% CI: 0.71–0.92, p=0.001) were less likely to be exposed to thirdhand smoke. Young people with junior high school education or higher, and current or former smokers, were more likely to be exposed to thirdhand smoke. There is room for improvement in the beliefs about thirdhand smoke among young people. Conclusions Thirdhand smoke exposure is an issue that should be addressed in public health policy. Young people with low income and current or former smokers are populations that should be mainly focused on in public education and prevention work on thirdhand smoke.

In this paper, we investigate the mixed solution of reduced biquaternion matrix equation $ \sum\limits_{i = 1}^nA_iX_iB_i = E $ with sub-matrix constraints. With the help of $ \mathcal{L_C} $-representation and the properties of vector operator based on semi-tensor product of reduced biquaternion matrices, the reduced biquaternion matrix equation (1.1) can be transformed into linear equations. A systematic method, $ \mathcal{GH} $-representation, is proposed to decrease the number of variables of a special unknown reduced biquaternion matrix and applied to solve the least squares problem of linear equations. Meanwhile, we give the necessary and sufficient conditions for the compatibility of reduced biquaternion matrix equation (1.1) under sub-matrix constraints. Numerical examples are given to demonstrate the results. The method proposed in this paper is applied to color image restoration.

Abstract Background Perfluorooctane sulfonic acid (PFOS) exposure has a negative impact on the environment and biological health. However, the relationship between PFOS exposure and diabetes in adults is not clear. Objective In this study, we included two distinct components: (1) in the cross-sectional analysis, we used data from the National Health and Nutrition Inspection Survey (NHANES) from 2015 to 2018 and eventually included 2539 subjects. The association between PFOS exposure and the risk of diabetes in adults was assessed by a logistic regression model, and further subgroup analysis was carried out according to sex, hypertension status and high cholesterol status. We adjusted for all covariates and found that the positive association between higher PFOS exposure and diabetes remained stable. (2) In vitro experiments were conducted as follows, rat insulinoma β cells (INS-1) were used as experimental materials; cell proliferation activity was detected using the MTT assay; quantitative real-time PCR was used to detect the mRNA expression of insulin; and Western blotting was used to detect insulin protein expression levels. Results Compared with Q1, the OR of the highest exposure level group (Q4) of PFOS was 1.342(95% CI 0.940, 1.916). We conducted a logistic regression analysis based on sex, hypertension, and high cholesterol stratification. Stratified by sex, we found that the exposure level of PFOS was significantly positively associated with diabetes (P for trend

Abstract Background Studies exploring whether metastatic organotropism and risk in gastric cancer (GC) differ by primary anatomical site are scarce. Methods This study included 15,260 and 1623 patients diagnosed with GC from the Surveillance, Epidemiology, and End Results (SEER) registry database and the Nanfang Hospital in China, respectively. Patients were stratified according to primary site of GC, and the incidence of metastasis to different organs was used to determine the metastatic organotropism for each GC subsite. Finally, the metastatic organotropism and risk were compared among the different subsite groups. Results Liver metastasis was the most common metastasis site in cardia GC, whereas other‐site metastases were more common in the body, antrum, overlapping lesions, and unspecified GCs. Liver and other‐site metastases were also frequently observed in the fundus, pylorus, lesser curvature, and greater curvature GCs. Patients with GC with definite primary tumor sites in the SEER and validation Nanfang hospital cohorts were compared by grouping as proximal and distal GCs for further analysis. In the SEER cohort, the top three metastatic sites of proximal GC were liver (21.4%), distant lymph node (LN) (14.6%), and other‐site (mainly peritoneum, 11.9%), whereas those of distal GC were other‐site (mainly peritoneum, 19.5%), liver (11.8%), and distant LN (9.5%). The incidence of metastasis to the liver, distant LN, lung, and brain was significantly higher in patients with proximal GC than in those with distal GC in both the SEER and Nanfang cohorts (p

Abstract Macrophage filopodia, which are dynamic nanotube-like protrusions, have mainly been studied in the context of pathogen clearance. The mechanisms by which they facilitate intercellular communication and mediate tissue inflammation remain poorly understood. Here, we show that macrophage filopodia produce a unique membrane structure called “filopodial tip vesicle” (FTV) that originate from the tip of macrophages filopodia. Filopodia tip-derived particles contain numerous internal-vesicles and function as cargo storage depots via nanotubular transport. Functional studies indicate that the shedding of FTV from filopodia tip allows the delivery of many molecular signalling molecules to fibroblasts. We observed that FTV derived from M1 macrophages and high glucose (HG)-stimulated macrophages (HG/M1-ftv) exhibit an enrichment of the chemokine IL11, which is critical for fibroblast transdifferentiation. HG/M1-ftv induce renal interstitial fibrosis in diabetic mice, while FTV inhibition or targeting FTV IL11- alleviates renal interstitial fibrosis, suggesting that the HG/M1-ftv IL11 pathway may be a novel mechanism underlying renal fibrosis in diabetic nephropathy. Collectively, FTV release could represent a novel function by which filopodia contribute to cell biological processes, and FTV is potentially associated with macrophage filopodia-related fibrotic diseases. Video Abstract

The ability to recognize the body sizes of sheep is significantly influenced by posture, especially without artificial fixation, leading to more noticeable changes. This study presents a recognition model using the Mask R-CNN convolutional neural network to identify the sides and backs of sheep. The proposed approach includes an algorithm for extracting key frames through mask calculation and specific algorithms for head-down, head-up, and jumping postures of Ujumqin sheep. The study reported an accuracy of 94.70% in posture classification. We measured the body size parameters of Ujumqin sheep of different sexes and in different walking states, including observations of head-down and head-up. The errors for the head-down position of rams, in terms of body slanting length, withers height, hip height, and chest depth, were recorded as 0.08 ± 0.06, 0.09 ± 0.07, 0.07 ± 0.05, and 0.12 ± 0.09, respectively. For rams in the head-up position, the corresponding errors were 0.06 ± 0.05, 0.06 ± 0.05, 0.07 ± 0.05, and 0.13 ± 0.07, respectively. The errors for the head-down position of ewes, in terms of body slanting length, withers height, hip height, and chest depth, were recorded as 0.06 ± 0.05, 0.09 ± 0.08, 0.07 ± 0.06, and 0.13 ± 0.10, respectively. For ewes in the head-up position, the corresponding errors were 0.06 ± 0.05, 0.08 ± 0.06, 0.06 ± 0.04, and 0.16 ± 0.12, respectively. The study observed that sheep walking through a passage exhibited a more curved knee posture compared to normal measurements, often with a lowered head. This research presents a cost-effective data collection scheme for studying multiple postures in animal husbandry.

Abstract Inflammation contributes to development of idiopathic pulmonary arterial hypertension (IPAH), and tumor biomarkers can reflect inflammatory and immune status. We aimed to determine the value of tumor biomarkers in IPAH comprehensively. We enrolled 315 patients with IPAH retrospectively. Tumor biomarkers were correlated with established indicators of pulmonary hypertension severity. Multivariable Cox regression found that AFP (hazard ratio [HR]: 1.587, 95% confidence interval [CI]: 1.014–2.482, p = 0.043) and CA125 (HR: 2.018, 95% CI: 1.163–3.504, p = 0.013) could independently predict prognosis of IPAH. The changes of AFP over time were associated with prognosis of patients, each 1 ng/mL increase in AFP was associated with 5.4% increased risk of clinical worsening (HR: 1.054, 95% CI: 1.001–1.110, p = 0.046), enabling detection of disease progression. Moreover, beyond well‐validated PH biomarkers, CA125 was still of prognostic value in the low‐risk patients (HR: 1.014, 95% CI: 1.004–1.024, p = 0.004), allowing for more accurate risk stratification and prediction of disease outcomes. AFP and CA125 can serve for prognosis prediction, risk stratification, and dynamic monitor in patients with IPAH.

The human gut microbiome plays a critical role in maintaining our health. Fluctuations in the diversity and structure of the gut microbiota have been implicated in the pathogenesis of several metabolic and inflammatory conditions. Dietary patterns, medication, smoking, alcohol consumption, and physical activity can all influence the abundance of different types of microbiota in the gut, which in turn can affect the health of individuals. Intestinal phages are an essential component of the gut microbiome, but most studies predominantly focus on the structure and dynamics of gut bacteria while neglecting the role of phages in shaping the gut microbiome. As bacteria-killing viruses, the distribution of bacteriophages in the intestine, their role in influencing the intestinal microbiota, and their mechanisms of action remain elusive. Herein, we present an overview of the current knowledge of gut phages, their lifestyles, identification, and potential impact on the gut microbiota.