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Bone, renowned for its elegant hierarchical structure and unique mechanical properties, serves as a constant source of inspiration for the development of synthetic materials. However, achieving accurate replication of bone features in artificial materials with remarkable structural and mechanical similarity remains a significant challenge. In this study, we employed a cascade of continuous fabrication processes, including biomimetic mineralization of collagen, bidirectional freeze-casting, and pressure-driven fusion, to successfully fabricate a macroscopic bulk material known as artificial compact bone (ACB). The ACB material closely replicates the composition, hierarchical structures, and mechanical properties of natural bone. It demonstrates a lamellated alignment of mineralized collagen (MC) microfibrils, similar to those found in natural bone. Moreover, the ACB exhibits a similar high mineral content (70.9 %) and density (2.2 g/cm3) as natural cortical bone, leading to exceptional mechanical properties such as high stiffness, hardness, and flexural strength that are comparable to those of natural bone. Importantly, the ACB also demonstrates excellent mechanical properties in wet, outstanding biocompatibility, and osteogenic properties in vivo, rendering it suitable for a broad spectrum of biomedical applications, including orthopedic, stomatological, and craniofacial surgeries.

Chronic kidney disease-mineral and bone disorder (CKD-MBD) has a direct impact on patients' quality of life, hospitalization rates and fracture risk. In recent years, osteoblasts and osteoclasts have become central to the pathophysiology of CKD-MBD. Osteoblasts interact with other organs by synthesizing fibroblast growth factor-23 (FGF-23) and sclerostin (SOST), making the skeleton an endocrine organ. Therefore, dysregulation of osteoblast differentiation is an important early event in the pathogenesis of CKD. In this paper, we systematically discuss the metabolic pathways of osteoblasts and the mechanisms related to the altered metabolic reprogramming of osteoblasts in the early CKD-MBD pathology. This paper shows that abnormalities in signaling pathways and metabolites such as Wnt/β-catenin, FGF-23, uremic toxins, metabolic acidosis, can alter the metabolic activity of osteoblasts, causing impaired maturation of the osteogenic spectrum, which in turn affects bone remodeling, which will provide a new way of thinking for explaining the pathological changes in renal bone disease and developing clinical treatment options.

Introduction: The causal association between modifiable risk factors and erectile dysfunction (ED) remains unclear, which hinders the early identification and intervention of patients with ED. The present study aimed to clarify the causal association between 42 predominant risk factors and ED. Methods: Univariate Mendelian Randomization (MR), multivariate MR, and mediation MR analyses were used to investigate the causal association between 42 modifiable risk factors and ED. Combined results were pooled from two independent ED genome-wide association studies to verify the findings. Results: Genetically predicted body mass index (BMI), waist circumference, trunk fat mass, whole body fat mass, poor overall health rating, type 2 diabetes, basal metabolic rate, adiponectin, cigarette consumption, insomnia, snoring, hypertension, stroke, ischemic stroke, coronary heart disease, myocardial infarction, heart failure, and major depressive disorder were found to increase the risk of ED (all P 0.05). Genetic predisposition to higher sex hormone-binding globulin (SHBG) levels could decrease the risk of ED (P 0.05). Conclusion: This comprehensive MR study supported the causal role of obesity, type 2 diabetes, basal metabolic rate, poor self-health rating, cigarette and alcohol consumption, insomnia and snoring, depression, hypertension, stroke, ischemic stroke, coronary heart disease, myocardial infarction, heart failure, SHBG, and adiponectin in the onset and development of ED.

Abstract The mechanisms of adenosine and specific adenosine receptor subtypes in promoting penile rehabilitation remain unclear. Single‐cell RNA sequencing of human corpus cavernosum, adenosine deaminase (ADA) and adenosine receptors knock‐out mice (ADA−/−, A1−/−, A2a−/−, A2b−/−, and A3−/−), and primary corpus cavernosum smooth muscle cells are used to determine receptor subtypes responsible for adenosine‐induced erection. Three rat models are established to characterize refractory erectile dysfunction (ED): age‐related ED, bilateral cavernous nerve crush related ED (BCNC), and diabetes mellitus‐induced ED. In single‐cell RNA sequencing data, the corpus cavernosum of ED patients show a decrease in adenosine A1, A2a and A2b receptors. In vivo, A2b receptor knock‐out abolishes adenosine‐induced erection but not that of A1, A2a, or A3 receptor. Under hypoxic conditions in vitro, activating the A2b receptor increases HIF‐1α and decreases PDE5 expression. In refractory ED models, activating the A2b receptor with Bay 60–6583 improves erectile function and down‐regulates HIF‐1α and TGF‐β. Administering Dipyridamole (40 mg Kg−1) to BCNC rats improve penile adenosine levels and erectile function. Our study reveals that the A2b receptor mediates adenosine‐induced penile erection. Activating the A2b receptor promotes penile rehabilitation of refractory ED by alleviating hypoxia and fibrosis.

Abstract The contact resistivity originating from the metal–semiconductor interface is a crucial factor for conversion efficiency of thermoelectric films devices. Due to anisotropic nature of state‐of‐art Bi2Te3 films, the contact resistivity also needs to match with the different orientations in/out‐plane film configurations. Here, a series of bismuth telluride (Bi2Te3) films with different orientations are deposited, and the contact resistivity between Ti/Cr/Cu and Bi2Te3‐based films is studied in detail. The increased (00l) orientation can effectively reduce the contact resistivity mainly due to the enhanced Tunneling effect. Finally, a low contact resistivity of 0.84 µΩ cm2 is observed in highly (00l)‐orientated Bi2Te3 film in contact with Cr. This work provides an effective method to control contact resistivity by adjusting the orientation of film, and also provides guidance on how to further improve the performance of thin film‐TEDs with different configurations.

Chronic kidney disease (CKD) is prevalent globally with limited therapeutic drugs available. To systemically identify novel proteins involved in the pathogenesis of CKD and possible therapeutic targets, we integrated human plasma proteomes with the genome-wide association studies (GWASs) of CKD, estimated glomerular filtration rate (eGFR) and blood urea nitrogen (BUN) to perform proteome-wide association study (PWAS), Mendelian Randomization and Bayesian colocalization analyses. The single-cell RNA sequencing data of healthy human and mouse kidneys were analyzed to explore the cell-type specificity of identified genes. Functional enrichment analysis was conducted to investigate the involved signaling pathways. The PWAS identified 22 plasma proteins significantly associated with CKD. Of them, the significant associations of three proteins (INHBC, LMAN2, and SNUPN) were replicated in the GWASs of eGFR, and BUN. Mendelian Randomization analyses showed that INHBC and SNUPN were causally associated with CKD, eGFR, and BUN. The Bayesian colocalization analysis identified shared causal variants for INHBC in CKD, eGFR, and BUN (all PP4 > 0.75). The single-cell RNA sequencing revealed that the INHBC gene was sparsely scattered within the kidney cells. This proteomic study revealed that INHBC, LMAN2, and SNUPN may be involved in the pathogenesis of CKD, which represent novel therapeutic targets and warrant further exploration in future research.

Abstract Background The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome. Results In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P

M23C6 carbide can precipitate simultaneously on both sides of austenite grain boundary in Fe–15Mn–3Al-0.7C steel tempered at 600 °C. In this paper, the morphology and growth behavior of M23C6 are studied by means of OM, SEM and TEM. The results show that the morphology of M23C6 located on both sides of grain boundary is different. On one side of the grain boundary, the carbides appear to be dispersed and disconnected, each with an irregular particle-like morphology, while on the opposite side, they are dispersed along the grain boundary in a short-rod morphology, and the adjacent ones tend to join together to form a network structure. In fact, regardless of which side of the grain boundary the carbides are on, they exhibit a definite growth behavior, growing along the close-packed plane and grain boundary. Also, the morphology of M23C6 depends on the angle between the close-packed plane and the grain boundary. In addition, twin structures with the same orientation can be found in both austenite and M23C6. A notable distinction between them is that there is a flat twin plane in the austenite twin structure but not in the carbide twin structure. Therefore, this paper highlights that the formation of these two twin structures is different. The austenite twin structure is caused by quenching treatment, while the carbide twin structure is formed by a new method called “growing-contacting”.

Introduction: The bidirectional relationship between the brain cortex and cardiovascular diseases (CVDs) remains inadequately explored. Methods: This study used bidirectional Mendelian randomization (MR) analysis to explore the interactions between nine phenotypes associated with hypertension, heart failure, atrial fibrillation (AF), and coronary heart disease (CHD), and brain cortex measurements. These measurements included total surface area (SA), average thickness (TH), and the SA and TH of 34 regions defined by the Desikan-Killiany atlas. The nine traits were obtained from sources such as the UK Biobank and FinnGen, etc., while MRI-derived traits of cortical structure were sourced from the ENIGMA Consortium. The primary estimate was obtained using the inverse-variance weighted approach. A false discovery rate adjustment was applied to the p-values (resulting in q-values) in the analyses of regional cortical structures. Results: A total of 1,260 two-sample MR analyses were conducted. Existing CHD demonstrated an influence on the SA of the banks of the superior temporal sulcus (bankssts) (q=0.018) and the superior frontal lobe (q=0.018), while hypertension was associated with changes in the TH of the lateral occipital region (q=0.02). Regarding the effects of the brain cortex on CVD incidence, total SA was significantly associated with the risk of CHD. Additionally, 16 and 3 regions exhibited significant effects on blood pressure and AF risk, respectively (q

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 This study aimed to evaluate the pharmacokinetics (PKs), safety, and immunogenicity of the biosimilar HEC14028 compared to reference Trulicity® (dulaglutide) in healthy male Chinese subjects. This study was a single‐center, randomized, open, single‐dose, parallel‐controlled comparative Phase I clinical trial, including a screening period of up to 14 days, a 17‐day observation period after administration, and a 7‐day safety follow‐up period. A total of 68 healthy male subjects were randomly assigned (1:1) to the test group (HEC14028) and the reference group (dulaglutide) (single 0.75 mg abdominal subcutaneous dose). The primary objective was to evaluate the pharmacokinetic characteristics of HEC14028 and compare the pharmacokinetic similarities between HEC14028 and dulaglutide. The primary PK endpoints were maximum plasma concentration (Cmax) and area under the blood concentration‐time curve from zero time to the estimated infinite time (AUC0–∞). The study results showed that HEC14028 and dulaglutide were pharmacokinetically equivalent: 90% confidence interval (CI) of Cmax and AUC0–∞ geometric mean ratios were 102.9%–122.0% and 97.1%–116.9%, respectively, which were both within the range of 80.00%–125.00%. No grade 3 or above treatment emergent adverse events (TEAEs), serious adverse events (SAEs), TEAEs leading to withdrawal from the trial, or TEAEs leading to death were reported in this study. Both HEC14028 and dulaglutide showed good and similar safety profiles, and no incremental immunogenicity was observed in subjects receiving HEC14028 and dulaglutide.

This study established a residue detection method based on the QuEChERS pre-treatment method and combined it with high-performance liquid chromatography–tandem mass spectrometry to test six herbicides (metamitron, clopyralid, desmedipham, phenmedipham, ethofumesate, and haloxyfop-p-methyl) in sugar beet plants, soil, and roots. The degradation dynamics and terminal residues of each herbicide in sugar beets were analysed. Finally, the dietary risks of various herbicides in sugar beets were evaluated based on the dietary structure of Chinese people, and the risk quotient values were below 100%. Using this detection method, all reagents exhibited good linearity (0.9724 ≤ R2 ≤ 0.9998), The limit of quantification (LOQ) ranged from 0.01 to 0.05 mg/L, the matrix effect ranged from −1.2% to −50%, the addition recovery rate ranged from 77.00% to 103.48%, and the relative standard deviation ranged from 1.61% to 16.17%; therefore, all indicators of this method met the residue detection standards. Under field conditions, the half-lives (t1/2) ranged about 0.65 ∼ 2.96 d and 0.38 ∼ 27.59 d in sugar beet plants and soil, respectively. All herbicides were easily degraded in sugar beet plants and soil (t1/2 < 30 d). The terminal residue amounts in the beet plants, soil, and roots ranged from < LOQ to 0.243 mg/kg. The dietary risk assessment of each pesticide was conducted based on the residual median of the terminal residues and the highest residual values on the edible part of the beetroot. The chronic exposure risk quotient (RQc) and acute exposure risk quotient (RQa) values were < 100%, indicating that the residue of each pesticide in beetroot posed low risks to consumers in China at the recommended dosage.

Abstract Background Stem cell sheet implantation offers a promising avenue for spinal cord injury (SCI) and is currently under investigation in pre-clinical in vivo studies. Nevertheless, a systematic review of the relevant literature is yet to be performed. Thus, this systematic review aims to explore the efficacy of stem cell sheet technology in treating SCI, as indicated by experimental animal model studies. Methods We searched PubMed, EMBASE, and Web of Science. Manuscripts that did not pertain to in vivo pre-clinical studies and those published in non-English languages were excluded. A risk assessment for bias was performed using the SYRCLE tool. Extracted data were synthesized only qualitatively because the data were not suitable for conducting the meta-analysis. Results Among the 847 studies retrieved from electronic database searches, seven met the inclusion criteria. Six of these studies employed a complete transection model, while one utilized a compression model. Stem cell sources included bone marrow mesenchymal stem cells, stem cells from human exfoliated deciduous teeth, and adipose-derived mesenchymal stem cells. In all included studies, stem cell sheet application significantly improved motor and sensory functional scores compared to intreated SCI rats. This functional recovery correlated with histological improvements at the injury site. All studies are at low risk of bias but certain domains were not reported by some or all of the studies. Conclusion The results of our systematic review suggest that stem cell sheets may be a feasible therapeutic approach for the treatment of SCI. Future research should be conducted on stem cell sheets in various animal models and types of SCI, and careful validation is necessary before translating stem cell sheets into clinical studies.

Abstract The darkbarbel catfish (Pelteobagrus vachelli), an economically important aquaculture species in China, is extensively employed in hybrid yellow catfish production due to its superior growth rate. However, information on its genome has been limited, constraining further genetic studies and breeding programs. Leveraging the power of PacBio long-read sequencing and Hi-C technologies, we present a high-quality, chromosome-level genome assembly for the darkbarbel catfish. The resulting assembly spans 692.10 Mb, with an impressive 99.9% distribution over 26 chromosomes. The contig N50 and scaffold N50 are 13.30 Mb and 27.55 Mb, respectively. The genome is predicted to contain 22,109 protein-coding genes, with 96.1% having functional annotations. Repeat elements account for approximately 35.79% of the genomic landscape. The completeness of darkbarbel catfish genome assembly is highlighted by a BUSCO score of 99.07%. This high-quality genome assembly provides a critical resource for future hybrid catfish breeding, comparative genomics, and evolutionary studies in catfish and other related species.