Unlocking the Transcriptional Control of NCAPG in Bovine Myoblasts: CREB1 and MYOD1 as Key Players.

Muscle formation directly determines meat production and quality. The non-SMC condensin I complex subunit G (NCAPG) is strongly linked to the growth features of domestic animals because it is essential in controlling muscle growth and development. This study aims to elucidate the tissue expression level of the bovine NCAPG gene, and determine the key transcription factors for regulating the bovine NCAPG gene. In this study, we observed that the bovine NCAPG gene exhibited high expression levels in longissimus dorsi and spleen tissues. Subsequently, we cloned and characterized the promoter region of the bovine NCAPG gene, consisting of a 2039 bp sequence, through constructing the deletion fragment double-luciferase reporter vector and site-directed mutation-identifying core promoter region with its key transcription factor binding site. In addition, the key transcription factors of the core promoter sequence of the bovine NCAPG gene were analyzed and predicted using online software. Furthermore, by integrating overexpression experiments and the electrophoretic mobility shift assay (EMSA), we have shown that cAMP response element binding protein 1 (CREB1) and myogenic differentiation 1 (MYOD1) bind to the core promoter region (-598/+87), activating transcription activity in the bovine NCAPG gene. In conclusion, these findings shed important light on the regulatory network mechanism that underlies the expression of the NCAPG gene throughout the development of the muscles in beef cattle.

Transcriptome Analysis of mRNA and lncRNA Related to Muscle Growth and Development in Gannan Yak and Jeryak.

The production performance of Jeryak, resulting from the F1 generation of the cross between Gannan yak and Jersey cattle, exhibits a significantly superior outcome compared with that of Gannan yak. Therefore, we used an RNA-seq approach to identify differentially expressed mRNAs (DEMs) and differentially expressed lncRNAs (DELs) influencing muscle growth and development in Gannan yaks and Jeryaks. A total of 304 differentially expressed lncRNAs and 1819 differentially expressed mRNAs were identified based on the screening criteria of |log 2 FC| > 1 and FDR < 0.05. Among these, 132 lncRNAs and 1081 mRNAs were found to be down-regulated, while 172 lncRNAs and 738 mRNAs were up-regulated. GO and KEGG analyses showed that the identified DELs and DEMs were enriched in the entries of pathways associated with muscle growth and development. On this basis, we constructed an lncRNA-mRNA interaction network. Interestingly, two candidate DELs (MSTRG.16260.9 and MSTRG.22127.1) had targeting relationships with 16 (MYC, IGFBP5, IGFBP2, MYH4, FGF6, etc.) genes related to muscle growth and development. These results could provide a basis for further studies on the roles of lncRNAs and mRNAs in muscle growth in Gannan yaks and Jeryak breeds.

Comprehensive Analysis of miRNA and mRNA Expression Profiles during Muscle Development of the Longissimus Dorsi Muscle in Gannan Yaks and Jeryaks.

A hybrid offspring of Gannan yak and Jersey cattle, the Jeryak exhibits apparent hybrid advantages over the Gannan yak in terms of production performance and other factors. The small non-coding RNAs known as miRNAs post-transcriptionally exert a significant regulatory influence on gene expression. However, the regulatory mechanism of miRNA associated with muscle development in Jeryak remains elusive. To elucidate the regulatory role of miRNAs in orchestrating skeletal muscle development in Jeryak, we selected longissimus dorsi muscle tissues from Gannan yak and Jeryak for transcriptome sequencing analysis. A total of 230 (DE) miRNAs were identified in the longissimus dorsi muscle of Gannan yak and Jeryak. The functional enrichment analysis revealed a significant enrichment of target genes from differentially expressed (DE)miRNAs in signaling pathways associated with muscle growth, such as the Ras signaling pathway and the MAPK signaling pathway. The network of interactions between miRNA and mRNA suggest that some (DE)miRNAs, including miR-2478-z, miR-339-x, novel-m0036-3p, and novel-m0037-3p, played a pivotal role in facilitating muscle development. These findings help us to deepen our understanding of the hybrid dominance of Jeryaks and provide a theoretical basis for further research on the regulatory mechanisms of miRNAs associated with Jeryak muscle growth and development.

CH02 peptide promotes ex vivo expansion of umbilical cord blood-derived CD34 + hematopoietic stem/progenitor cells.

Umbilical cord blood (UCB) is an advantageous source for hematopoietic stem/progenitor cell (HSPC) transplantation, yet the current strategies for large-scale and cost-effective UCB-HSPC preparation are still unavailable. To overcome these obstacles, we systematically evaluate the feasibility of our newly identified CH02 peptide for ex vivo expansion of CD34 + UCB-HSPCs. We herein report that the CH02 peptide is specifically enriched in HSPC proliferation via activating the FLT3 signaling. Notably, the CH02-based cocktails are adequate for boosting 12-fold ex vivo expansion of UCB-HSPCs. Meanwhile, CH02-preconditioned UCB-HSPCs manifest preferable efficacy upon wound healing in diabetic mice via bidirectional orchestration of proinflammatory and anti-inflammatory factors. Together, our data indicate the advantages of the CH02-based strategy for ex vivo expansion of CD34 + UCB-HSPCs, which will provide new strategies for further development of large-scale HSPC preparation for clinical purposes.

FGFR4 and EZH2 inhibitors synergistically induce hepatocellular carcinoma apoptosis via repressing YAP signaling.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide, but current treatment options remain limited and cause serious life-threatening side effects. Aberrant FGFR4 signaling has been validated as an oncogenic driver of HCC, and EZH2, the catalytic subunit of the PRC2 complex, is a potential factor that contributes to acquired drug resistance in many tumors, including HCC. However, the functional relationship between these two carcinogenic factors, especially their significance for HCC treatment, remains unclear. In this study, we systematically evaluated the feasibility of a combination therapy targeting FGFR4 and EZH2 for HCC. METHODS: RNA sequencing data of patients with Liver hepatocellular carcinoma (LIHC) from The Cancer Genome Atlas (TCGA) were analyzed to determine FGFR4 and EZH2 expression and their interaction with prognosis. Moreover, the HCC cell lines, zebrafish/mouse HCC xenografts and zebrafish HCC primary tumors were treated with FGFR4 inhibitor (Roblitinib) and/or EZH2 inhibitor (CPI-169) and then subjected to cell proliferation, viability, apoptosis, and tumor growth analyses to evaluate the feasibility of combination therapy for HCC both in vitro and in vivo. Furthermore, RNA-Seq was performed in combination with ChIP-Seq data analysis to investigate the critical mechanism underlying the combination treatment with Roblitinib and CPI-169. RESULTS: EZH2 accumulated through the non-canonical NF-kB signaling in response to FGFR4 inhibitor treatment, and the elevated EZH2 levels led to the antagonism of HCC against Roblitinib (FGFR4 inhibitor). Notably, knockdown of EZH2 sensitized HCC cells to Roblitinib, while the combination treatment of Roblitinib and CPI-169 (EZH2 inhibitor) synergistically induced the HCC cell apoptosis in vitro and suppressed the zebrafish/mouse HCC xenografts and zebrafish HCC primary tumors development in vivo. Moreover, Roblitinib and CPI-169 synergistically inhibited HCC development via repressing YAP signaling. CONCLUSIONS: Collectively, our study highlighted the potential of the therapeutic combination of FGFR4 and EZH2 inhibitors, which would provide new references for the further development of clinical treatment strategies for HCC.

Inhibition of FGFR2 Signaling by Cynaroside Attenuates Liver Fibrosis.

Liver fibrosis represents a significant health hazard with a high morbidity rate and an increased risk of liver cancer. Targeting overactivated Fibroblast growth factor receptor 2 (FGFR2) is a promising strategy to counteract collagen accumulation during liver fibrosis. However, there is a shortage of drugs to specifically block the activation of FGFR2 in liver fibrosis patients. Data mining, cell validation, and animal studies showed a positive correlation between FGFR2 overexpression and liver fibrosis development. Novel FGFR2 inhibitors were screened using a microarray-based high-throughput binding analysis. The effectiveness of each candidate was validated through simulated docking, binding affinity verification, single-point mutation validation, and in vitro kinase inhibition measurements to demonstrate the ability of each inhibitor to block the catalytic pocket and reverse FGFR2 overactivation. A specific FGFR2 inhibitor, cynaroside (CYN, also known as luteoloside), was screened based on the finding that FGFR2 promotes hepatic stellate cell (HSC) activation and collagen secretion in hepatocytes. The results from cellular assays showed that CYN can inhibit FGFR2 hyperactivation resulting from its overexpression and excessive basic fibroblast growth factor (bFGF), reducing HSC activation and collagen secretion in hepatocytes. Animal experiments on a carbon tetrachloride (CCl4) mouse model and a nonalcoholic steatohepatitis mouse model indicate that CYN treatment reduces liver fibrosis during fibrosis formation. These findings suggest that CYN prevents liver fibrosis formation at the cell level and in mouse models.

Comparison of Half-Effective Concentration of Propofol in Patients with Parkinson's Disease and Non-Parkinson's Disease.

Objective: This study aimed to compare the half-effective concentration (EC50) of propofol required for the bispectral index (BIS) 50 in patients with Parkinson's disease (PD) and non-PD (NPD) during induction by the Dixon's improved sequential method. Methods: This prospective study recruited 20 patients with PD undergoing deep brain stimulation and 20 patients with NPD accompanied by meningioma or glioma undergoing intracranial surgery from March 2018 to March 2019. The patients were induced by propofol via target-controlled infusion. The target effect-site concentration of propofol was determined by the Dixon's improved sequential method. The results of the pilot experiment showed that the target effect-site concentration for the first patient with PD and NPD was 3.5 µg/mL and 2.8 µg/mL, respectively. BIS values were recorded after achieving a constant effect-site concentration of propofol. The increment or decrement of the target effect-site concentration of the next patient was 0.1 µg/mL. Results: Demographic data, general physical condition, and hemodynamic values were similar between the PD and the NPD groups. The target effect-site concentration of propofol induction doses was significantly higher in the PD group than in the NPD group. The EC50 of propofol required for BIS 50 was 3.213 µg/mL [95% confidence interval (CI), 3.085-3.287 µg/mL] in the PD group and 2.77 µg/mL (95% CI, 2.568-2.977 µg/mL) in the NPD group. Conclusion: The EC50 of propofol required for BIS 50 was higher in patients with PD than in patients with NPD.

Turning gray selenium and sublimed sulfur into a nanocomposite to accelerate tissue regeneration by isothermal recrystallization.

BACKGROUND: Globally, millions of patients suffer from regenerative deficiencies, such as refractory wound healing, which is characterized by excessive inflammation and abnormal angiogenesis. Growth factors and stem cells are currently employed to accelerate tissue repair and regeneration; however, they are complex and costly. Thus, the exploration of new regeneration accelerators is of considerable medical interest. This study developed a plain nanoparticle that accelerates tissue regeneration with the involvement of angiogenesis and inflammatory regulation. METHODS: Grey selenium and sublimed sulphur were thermalized in PEG-200 and isothermally recrystallised to composite nanoparticles (Nano-Se@S). The tissue regeneration accelerating activities of Nano-Se@S were evaluated in mice, zebrafish, chick embryos, and human cells. Transcriptomic analysis was performed to investigate the potential mechanisms involved during tissue regeneration. RESULTS: Through the cooperation of sulphur, which is inert to tissue regeneration, Nano-Se@S demonstrated improved tissue regeneration acceleration activity compared to Nano-Se. Transcriptome analysis revealed that Nano-Se@S improved biosynthesis and ROS scavenging but suppressed inflammation. The ROS scavenging and angiogenesis-promoting activities of Nano-Se@S were further confirmed in transgenic zebrafish and chick embryos. Interestingly, we found that Nano-Se@S recruits leukocytes to the wound surface at the early stage of regeneration, which contributes to sterilization during regeneration. CONCLUSION: Our study highlights Nano-Se@S as a tissue regeneration accelerator, and Nano-Se@S may provide new inspiration for therapeutics for regenerative-deficient diseases.

Hyaluronic acid-FGF2-derived peptide bioconjugates for suppression of FGFR2 and AR simultaneously as an acne antagonist.

Acne is a chronic skin condition that has serious consequences for mental and social well-being because it frequently occurs on the face. Several acne treatment approaches have commonly been used but have been hampered by side effects or weak activity. Thus, the investigation of the safety and efficacy of anti-acne compounds is of considerable medical importance. Herein, an endogenous peptide (P5) derived from fibroblast growth factors 2 (FGF2) was conjugated to the polysaccharide hyaluronic acid (HA) to generate the bioconjugate nanoparticle HA-P5, which suppresses fibroblast growth factor receptors (FGFRs) to significantly rehabilitate acne lesions and reduce sebum accumulation in vivo and in vitro. Moreover, our results show that HA-P5 inhibits both fibroblast growth factor receptor 2 (FGFR2) and androgen receptor (AR) signalling in SZ95 cells, reverses the acne-prone transcriptome, and decreases sebum secretion. Furthermore, the cosuppression mechanism revealed that HA-P5 blocks FGFR2 activation, as well as the YTH N6-methyladenosine RNA binding protein F3 (YTHDF3) downstream molecules, including an N6-methyladenosine (m6A) reader that facilitates AR translation. More importantly, a significant difference between HA-P5 and the commercial FGFR inhibitor AZD4547 is that HA-P5 does not trigger the overexpression of aldo-keto reductase family 1 member C3 (AKR1C3), which blocks acne treatment by catalyzing the synthesis of testosterone. Overall, we demonstrate that a polysaccharide-conjugated and naturally derived oligopeptide HA-P5 can alleviate acne and act as an optimal FGFR2 inhibitor and reveal that YTHDF3 plays a crucial role in signalling between FGFR2 and AR.

Integration of ATAC-Seq and RNA-Seq Analysis to Identify Key Genes in the Longissimus Dorsi Muscle Development of the Tianzhu White Yak.

During the postnatal stages, skeletal muscle development undergoes a series of meticulously regulated alterations in gene expression. However, limited studies have employed chromatin accessibility to unravel the underlying molecular mechanisms governing muscle development in yak species. Therefore, we conducted an analysis of both gene expression levels and chromatin accessibility to comprehensively characterize the dynamic genome-wide chromatin accessibility during muscle growth and development in the Tianzhu white yak, thereby elucidating the features of accessible chromatin regions throughout this process. Initially, we compared the differences in chromatin accessibility between two groups and observed that calves exhibited higher levels of chromatin accessibility compared to adult cattle, particularly within ±2 kb of the transcription start site (TSS). In order to investigate the correlation between alterations in chromatin accessible regions and variations in gene expression levels, we employed a combination of ATAC-seq and RNA-seq techniques, leading to the identification of 18 central transcriptional factors (TFs) and 110 key genes with significant effects. Through further analysis, we successfully identified several TFs, including Sp1, YY1, MyoG, MEF2A and MEF2C, as well as a number of candidate genes (ANKRD2, ANKRD1, BTG2 and LMOD3) which may be closely associated with muscle growth and development. Moreover, we constructed an interactive network program encompassing hub TFs and key genes related to muscle growth and development. This innovative approach provided valuable insights into the molecular mechanism underlying skeletal muscle development in the postnatal stages of Tianzhu white yaks while also establishing a solid theoretical foundation for future research on yak muscle development.

Transcriptional analysis of microRNAs related to unsaturated fatty acid synthesis by interfering bovine adipocyte ACSL1 gene.

Long-chain fatty acyl-CoA synthase 1 (ACSL1) plays a vital role in the synthesis and metabolism of fatty acids. The proportion of highly unsaturated fatty acids in beef not only affects the flavor and improves the meat's nutritional value. In this study, si-ACSL1 and NC-ACSL1 were transfected in bovine preadipocytes, respectively, collected cells were isolated on the fourth day of induction, and then RNA-Seq technology was used to screen miRNAs related to unsaturated fatty acid synthesis. A total of 1,075 miRNAs were characterized as differentially expressed miRNAs (DE-miRNAs), of which the expressions of 16 miRNAs were upregulated, and that of 12 were downregulated. Gene ontology analysis indicated that the target genes of DE-miRNAs were mainly involved in biological regulation and metabolic processes. Additionally, KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis identified that the target genes of DE-miRNAs were mainly enriched in metabolic pathways, fatty acid metabolism, PI3K-Akt signaling pathway, glycerophospholipid metabolism, fatty acid elongation, and glucagon signaling pathway. Combined with the previous mRNA sequencing results, several key miRNA-mRNA targeting relationship pairs, i.e., novel-m0035-5p-ACSL1, novel-m0035-5p-ELOVL4, miR-9-X-ACSL1, bta-miR-677-ACSL1, miR-129-X-ELOVL4, and bta-miR-485-FADS2 were screened via the miRNA-mRNA interaction network. Thus, the results of this study provide a theoretical basis for further research on miRNA regulation of unsaturated fatty acid synthesis in bovine adipocytes.

Prophylactic administration of tranexamic acid combined with thromboelastography-guided hemostatic algorithm reduces allogeneic transfusion requirements during pediatric resective epilepsy surgery: A randomized controlled trial.

Background: Intraoperative bleeding and allogeneic transfusion remain common problems in pediatric resective epilepsy surgery. Tranexamic acid (TXA) is a widely recommended antifibrinolytic drug that reduces blood loss and transfusion requirements for bleeding patients. Thromboelastography (TEG)-guided hemostatic algorithm is commonly used in bleeding management. This trial was designed to validate the efficacy of a multimodal coagulation therapy involving continuous TXA infusion with TEG-guided hemostatic algorithm in reducing allogeneic exposure risk in pediatric resective epilepsy surgery. Methods: Eighty-three children undergoing resective epilepsy surgery were randomized into a treatment group (Group T; n = 42) and a control group (Group C; n = 41). Group T received prophylactic TXA (10 mg/kg followed by 5 mg/kg/h) with TEG-guided hemostatic algorithm, whereas Group C received conventional coagulation management. The primary outcome was allogeneic transfusion rate during surgery, and the secondary outcomes were intraoperative blood loss, incidence of postoperative seizures, and thromboembolic events during hospitalization. Results: The incidence of intraoperative allogeneic transfusion reduced by 34.7% with the use of a multimodal coagulation therapy (19.0% in Group T vs. 53.7% in Group C; RR 0.355, 95% CI 0.179-0.704; p = 0.001). This was mainly triggered by a significant reduction (44.1%) in intraoperative plasma transfusion (7.1% in Group T vs. 51.2% in Group C; RR 0.139, 95% CI 0.045-0.432; p = 0.000). The risk of intraoperative RBC transfusion was lower in Group T than in Group C, but the difference was not statistically significant (14.3% in Group T vs. 29.3% in Group C; RR 0.488, 95% CI 0.202-1.177; p = 0.098). No platelets were transfused in both groups. Further, 19 (45.2%) patients in Group T received fibrinogen concentrates guided by TEG data, whereas 1 (2.4%) patient in Group C received fibrinogen concentrates empirically. There were no significant differences in estimated blood loss and postoperative seizures between the two groups, and no thromboembolic events were observed after surgery. Conclusion: Prophylactic administration of TXA combined with TEG-guided hemostatic algorithm can be an effective multimodal coagulation strategy for reducing allogeneic transfusion requirements during pediatric resective epilepsy surgery. Clinical Trial Registration: www.chictr.org.cn/index.aspx, identifier ChiCTR1800016188.

Evaluation of novel plantar pressure-based 3-dimensional printed accommodative insoles - A feasibility study.

BACKGROUND: Custom insoles are commonly prescribed to patients with diabetes to redistribute plantar pressure and decrease the risk of ulceration. Advances in 3D printing have enabled the creation of 3D-printed personalized metamaterials whose properties are derived not only from the base material but also the lattice microstructures within the metamaterial. Insoles manufactured using personalized metamaterials have both patient-specific geometry and stiffnesses. However, the safety and biomechanical effect of the novel insoles have not yet been tested clinically. METHODS: Individuals without ulcer, neuropathy, or deformity were recruited for this study. In-shoe walking plantar pressure at baseline visit was taken and sensels with pressure over 200 kPa was used to define offloading region(s). Three pairs of custom insoles (two 3D printed insoles with personalized metamaterials (Hybrid and Full) designed based on foot shape and plantar pressure mapping and one standard-of-care diabetic insole as a comparator). In-shoe plantar pressure measurements during walking were recorded in a standardized research shoe and the three insoles and compared across all four conditions. FINDINGS: Twelve individuals were included in the final analysis. No adverse events occurred during testing. Maximum peak plantar pressure and the pressure time integral were reduced in the offloading regions in the Hybrid and Full but not in the standard-of-care compared to the research shoe. INTERPRETATION: This feasibility study confirms our ability to manufacture the 3D printed personalized metamaterials insoles and demonstrates their ability to reduce plantar pressure. We have demonstrated the ability to modify the 3D printed design to offload certain parts of the foot using plantar pressure data and a patient-specific metamaterials in the 3D printed insole design. The advance in 3D printed technology has shown its potential to improve current care.

A One-step strategy to target essential factors with auxin-inducible degron system in mouse embryonic stem cells.

The self-renewal and pluripotency of embryonic stem cells (ESCs) are conferred by networks including transcription factors and histone modifiers. The Auxin-inducible degron (AID) system can rapidly and reversibly degrade its target proteins and is becoming a powerful tool to explore novel function of key pluripotent and histone modifier genes in ESCs. However, the low biallelic tagging efficiency and a basal degradation level of the current AID systems deem it unsuitable to target key pluripotent genes with tightly controlled expression levels. Here, we develop a one-step strategy to successfully target and repress the endogenous pluripotent genes in mouse ESCs and replace their expression with AID fused transgenes. Therefore, this work provides an efficient way for employing the AID system to uncover novel function of essential pluripotent and chromatin modifier genes in ESCs.

General Method for the Amination of Aryl Halides with Primary and Secondary Alkyl Amines via Nickel Photocatalysis.

The Buchwald-Hartwig C-N coupling reaction has been ranked as one of the 20 most frequently used reactions in medicinal chemistry. Owing to its much lower cost and higher reactivity toward less reactive aryl chlorides than palladium, the C-N coupling reaction catalyzed by Ni-based catalysts has received a great deal of attention. However, there appear to be no universal, practical Ni catalytic systems so far that could enable the coupling of electron-rich and electron-poor aryl halides with both primary and secondary alkyl amines. In this study, it is reported that a Ni(II)-bipyridine complex catalyzes efficient C-N coupling of aryl chlorides and bromides with various primary and secondary alkyl amines under direct excitation with light. Intramolecular C-N coupling is also demonstrated. The feasibility and applicability of the protocol in organic synthesis is attested by more than 200 examples.

A novel workflow to fabricate a patient-specific 3D printed accommodative foot orthosis with personalized latticed metamaterial.

Patients with diabetes mellitus are at elevated risk for secondary complications that result in lower extremity amputations. Standard of care to prevent these complications involves prescribing custom accommodative insoles that use inefficient and outdated fabrication processes including milling and hand carving. A new thrust of custom 3D printed insoles has shown promise in producing corrective insoles but has not explored accommodative diabetic insoles. Our novel contribution is a metamaterial design application that allows the insole stiffness to vary regionally following patient-specific plantar pressure measurements. We presented a novel workflow to fabricate custom 3D printed elastomeric insoles, a testing method to evaluate the durability, shear stiffness, and compressive stiffness of insole material samples, and a case study to demonstrate how the novel 3D printed insoles performed clinically. Our 3D printed insoles results showed a matched or improved durability, a reduced shear stiffness, and a reduction in plantar pressure in clinical case study compared to standard of care insoles.

Cartilage contact characteristics of the knee during gait in individuals with obesity.

Obesity increases the risk of knee osteoarthritis (OA). Knee joint contact characteristics have been thought to provide insights into the pathogenesis of knee OA; however, the cartilage contact characteristics in individuals with obesity have not been fully described. We conducted cartilage-to-cartilage contact analyses through high-precision fluoroscopy imaging with subject-specific magnetic resonance cartilage models. Twenty-five individuals with obesity were recruited for this study, and previously published data consisted of eight nonobese individuals who were used as the comparator group. In both groups, knees were imaged by a dual fluoroscopic imaging system during treadmill walking, and the tibiofemoral cartilage contact locations were analyzed and described on the tibial plateau in the medial-lateral (ML) and anterior-posterior (AP) directions and on femoral condyle surfaces using contact angles in the sagittal plane and deviation angles in a plane perpendicular to the sagittal plane. On the medial tibial plateau, the ML contact locations in the individuals with obesity were located more medially than in the nonobese group throughout the stance phase. The medial plateau AP contact locations in individuals with obesity showed a different pattern compared with the nonobese group. The ML contact excursions on the medial plateau in the individuals with obesity were larger than in the nonobese group. These findings suggest that obesity affects the contact location mainly in the medial compartment, which explains, in part, the high prevalence of medial knee OA in the obese population.

Chiral Arylated Amines via C-N Coupling of Chiral Amines with Aryl Bromides Promoted by Light.

The Buchwald-Hartwig C-N coupling reaction has found widespread applications in organic synthesis. Over the past two decades or so, many improved catalysts have been introduced, allowing various amines and aryl electrophiles to be readily used nowadays. However, there lacks a protocol that could be used to couple a wide range of chiral amines and aryl halides, without erosion of the enantiomeric excess (ee). Reported in this article is a method based on molecular Ni catalysis driven by light, which enables stereoretentive C-N coupling of optically active amines, amino alcohols, and amino acid esters with aryl bromides, with no need for any external photosensitizer. The method is effective for a wide variety of coupling partners, including those bearing functional groups sensitive to bases and nucleophiles, thus providing a viable alternative to accessing synthetically important chiral N-aryl amines, amino alcohols, and amino acids esters. Its viability is demonstrated by 92 examples with up to 99 % ee.

Establishing Quality and Safety in Hospital-based 3D Printing Programs: Patient-first Approach.

The adoption of three-dimensional (3D) printing is rapidly spreading across hospitals, and the complexity of 3D-printed models and devices is growing. While exciting, the rapid growth and increasing complexity also put patients at increased risk for potential errors and decreased quality of the final product. More than ever, a strong quality management system (QMS) must be in place to identify potential errors, mitigate those errors, and continually enhance the quality of the product that is delivered to patients. The continuous repetition of the traditional processes of care, without insight into the positive or negative impact, is ultimately detrimental to the delivery of patient care. Repetitive tasks within a process can be measured, refined, and improved and translate into high levels of quality, and the same is true within the 3D printing process. The authors share their own experiences and growing pains in building a QMS into their 3D printing processes. They highlight errors encountered along the way, how they were addressed, and how they have strived to improve consistency, facilitate communication, and replicate successes. They also describe the vital intersection of health care providers, regulatory groups, and traditional manufacturers, who contribute essential elements to a common goal of providing quality and safety to patients. ©RSNA, 2021.