The Role of Perioperative Nutritional Status and Supplementation in Orthopaedic Surgery: A Review of Postoperative Outcomes.

¼ Identification of malnourished and at-risk patients should be a standardized part of the preoperative evaluation process for every patient.¼ Malnourishment is defined as a disorder of energy, protein, and nutrients based on the presence of insufficient energy intake, weight loss, muscle atrophy, loss of subcutaneous fat, localized or generalized fluid accumulation, or diminished functional status.¼ Malnutrition has been associated with worse outcomes postoperatively across a variety of orthopaedic procedures because malnourished patients do not have a robust metabolic reserve available for recovery after surgery.¼ Screening assessment and basic laboratory studies may indicate patients' nutritional risk; however, laboratory values are often not specific for malnutrition, necessitating the use of prognostic screening tools.¼ Nutrition consultation and perioperative supplementation with amino acids and micronutrients are 2 readily available interventions that orthopaedic surgeons can select for malnourished patients.

Cervical Spine Surgery Following COVID-19 Infection: When is it Safe to Proceed?

STUDY DESIGN: Retrospective. OBJECTIVE: We utilized the NIH National COVID Cohort Collaborative (N3C) database to characterize the risk profile of patients undergoing spine surgery during multiple time windows following the COVID-19 infection. SUMMARY OF BACKGROUND DATA: While the impact of COVID-19 on various organ systems is well documented, there is limited knowledge regarding its effect on perioperative complications following spine surgery or the optimal timing of surgery after an infection. METHODS: We asked the National COVID Cohort Collaborative for patients who underwent cervical spine surgery. Patients were stratified into those with an initial documented COVID-19 infection within 3 time periods: 0-2 weeks, 2-6 weeks, or 6-12 weeks before surgery. RESULTS: A total of 29,449 patients who underwent anterior approach cervical spine surgery and 46,379 patients who underwent posterior approach cervical spine surgery were included. Patients who underwent surgery within 2 weeks of their COVID-19 diagnosis had a significantly increased risk for venous thromboembolic events, sepsis, 30-day mortality, and 1-year mortality, irrespective of the anterior or posterior approach. Among patients undergoing surgery between 2 and 6 weeks after COVID-19 infection, the 30-day mortality risk remained elevated in patients undergoing a posterior approach only. Patients undergoing surgery between 6 and 12 weeks from the date of the COVID-19 infection did not show significantly elevated rates of any complications analyzed. CONCLUSIONS: Patients undergoing either anterior or posterior cervical spine surgery within 2 weeks from the initial COVID-19 diagnosis are at increased risk for perioperative venous thromboembolic events, sepsis, and mortality. Elevated perioperative complication risk does not persist beyond 2 weeks, except for 30-day mortality in posterior approach surgeries. On the basis of these results, it may be warranted to postpone nonurgent spine surgeries for at least 2 weeks following a COVID-19 infection and advise patients of the increased perioperative complication risk when urgent surgery is required.

Fano resonance in molecular junctions of spin crossover complexes.

In this paper, we introduce a novel molecular switch paradigm that integrates spin crossover complexes with the Fano resonance effect. Specifically, by performing density-functional theory calculations, the feasibility of achieving Fano resonance using spin crossover complexes is demonstrated in our designed molecular junctions using the complex {Fe[H2B(pz)2]2[Bp(bipy)]} [pz = 1-pyrazolyl, Bp(bipy) = bis(phenylethynyl)(2,2'-bipyridine)]. It is further revealed that the Fano resonance, particularly the Fano dip, is most prominent in the junction with cobalt tips among all the schemes, together with the spin-filtering effect. Most importantly, this junction of cobalt tips is able to exhibit three distinct conductance states, which are controlled by the modulation of Fano resonance due to the spin-state transition of the complex and the applied gate voltage. Such a molecular switch paradigm holds potential for applications in logic gates, memory units, sensors, thermoelectrics, and beyond.

Clinicopathological and molecular genetic alterations in monomorphic-epitheliotropic intestinal T-cell lymphoma of the small intestine.

BACKGROUND: Small intestinal monomorphic-epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma originating in the gastrointestinal tract. This study aimed to investigate the clinicopathological features, immunophenotypes, and molecular genetic changes of MEITL. METHODS: The clinicopathological data for three patients with surgically resected MEITL of the small intestine were collected. Next, immunohistochemical labeling, Epstein-Barr virus (EBV) in situ hybridization, assessment of clonal rearrangement of T-cell receptor (TCR) genes, and next-generation sequencing (NGS) were performed. RESULTS: Of the three patients, two were male and one was female, with ages of 61, 67, and 73 years, respectively. Clinical manifestations were predominantly abdominal pain and distension. Histopathology revealed infiltrative growth of small-to-medium-sized lymphocytes with a consistent morphology between the intestinal walls, accompanied by an obvious pro-epithelial phenomenon. The expression of CD3, CD8, CD43, CD56, TIA-1, CD103, H3K36me3, and Bcl-2 was detected, and the Ki-67 proliferation index ranged from 50% to 80%. All three patients tested negative for EBER. However, monoclonal rearrangement of the TCR gene was detected in them. NGS testing showed a JAK3 mutation in all three cases. Further, STAT5B, SETD2, and TP53 mutations were each observed in two cases, and a BCOR mutation was found in one case. All patients were treated with chemotherapy after surgery. Two patients died 7 and 15 month post-operation, and one patient survived for 5 months of follow-up. CONCLUSIONS: Our findings demonstrate that mutations in JAK3 and STAT5B of the JAK/STAT pathway and inactivation of the oncogene SETD2 markedly contribute to the lymphomagenesis of MEITL.

Unraveling a Concerted Proton-Coupled Electron Transfer Pathway in Atomically Precise Gold Nanoclusters.

Metal nanoclusters (MNCs) represent a promising class of materials for catalytic carbon dioxide and proton reduction as well as dihydrogen oxidation. In such reactions, multiple proton-coupled electron transfer (PCET) processes are typically involved, and the current understanding of PCET mechanisms in MNCs has primarily focused on the sequential transfer mode. However, a concerted transfer pathway, i.e., concerted electron-proton transfer (CEPT), despite its potential for a higher catalytic rate and lower reaction barrier, still lacks comprehensive elucidation. Herein, we introduce an experimental paradigm to test the feasibility of the CEPT process in MNCs, by employing Au18(SR)14 (SR denotes thiolate ligand), Au22(SR)18, and Au25(SR)18- as model clusters. Detailed investigations indicate that the photoinduced PCET reactions in the designed system proceed via an CEPT pathway. Furthermore, the rate constants of gold nanoclusters (AuNCs) have been found to be correlated with both the size of the cluster and the flexibility of the Au-S framework. This newly identified PCET behavior in AuNCs is prominently different from that observed in semiconductor quantum dots and plasmonic metal nanoparticles. Our findings are of crucial importance for unveiling the catalytic mechanisms of quantum-confined metal nanomaterials and for the future rational design of more efficient catalysts.

Costs of revision operations for distal junctional kyphosis following thoracic posterior spinal fusion for adolescent idiopathic scoliosis.

PURPOSE: To assess direct costs and risks associated with revision operations for distal junctional kyphosis/failure (DJK) following thoracic posterior spinal instrumented fusions (TPSF) for adolescent idiopathic scoliosis (AIS). METHODS: Children who underwent TPSF for AIS by a single surgeon (2014-2020) were reviewed. Inclusion criteria were minimum follow-up of 2 years, thoracolumbar posterior instrumented fusion with a lower instrumented vertebra (LIV) cranial to L2. Patients who developed DJK requiring revision operations were identified and compared with those who did not develop DJK. RESULTS: Seventy-nine children were included for analysis. Of these, 6.3% developed DJK. Average time to revision was 20.8 ± 16.2 months. Comparing index operations, children who developed DJK had significantly greater BMIs, significantly lower thoracic kyphosis postoperatively, greater post-operative lumbar Cobb angles, and significantly more LIVs cranial to the sagittal stable vertebrae (SSV), despite having statistically similar pre-operative coronal and sagittal alignment parameters and operative details compared with non-DJK patients. Revision operations for DJK, when compared with index operations, involved significantly fewer levels, longer operative times, greater blood loss, and longer hospital lengths of stay. These factors resulted in significantly greater direct costs for revision operations for DJK ($76,883 v. $46,595; p < 0.01). CONCLUSIONS: In this single-center experience, risk factors for development of DJK were greater BMI, lower post-operative thoracic kyphosis, and LIV cranial to SSV. As revision operations for DJK were significantly more costly than index operations, all efforts should be aimed at strategies to prevent DJK in the AIS population.

A colorimetric sensing strategy based on chitosan-stabilized platinum nanoparticles for quick detection of α-glucosidase activity and inhibitor screening.

α-Glucosidase (α-Glu) is implicated in the progression and pathogenesis of type II diabetes (T2D). In this study, we developed a rapid colorimetric technique using platinum nanoparticles stabilized by chitosan (Ch-PtNPs) to detect α-Glu activity and its inhibitor. The Ch-PtNPs facilitate the conversion of 3,3',5,5'-tetramethylbenzidine (TMB) into oxidized TMB (oxTMB) in the presence of dissolved O2. The catalytic hydrolysis of 2-O-α-D-glucopyranosyl-L-ascorbic acid (AA-2G) by α-Glu produces ascorbic acid (AA), which reduces oxTMB to TMB, leading to the fading of the blue color. However, the presence of α-Glu inhibitors (AGIs) hinders the generation of AA, allowing Ch-PtNPs to re-oxidize colorless TMB back to blue oxTMB. This unique phenomenon enables the colorimetric detection of α-Glu activity and AGIs. The linear range for α-Glu was found to be 0.1-1.0 U mL-1 and the detection limit was 0.026 U mL-1. Additionally, the half-maximal inhibition value (IC50) for acarbose, an α-Glu inhibitor, was calculated to be 0.4769 mM. Excitingly, this sensing platform successfully detected α-Glu activity in human serum samples and effectively screened AGIs. These promising findings highlight the potential application of the proposed strategy in clinical diabetes diagnosis and drug discovery.

Ni-doping effects on formation and migration of oxygen vacancies in SrFe1-xNixO3-δ oxygen carriers.

Ni is a promising B-site doping element capable of improving the oxygen carrier performance of SrFeO3 perovskite. In this work, the effect of Ni doping on the formation and migration of oxygen vacancies in SrFe1-xNixO3-δ (x = 0, 0.0625, 0.125, 0.1875, and 0.25) is investigated using density functional theory calculations. Our results show that the oxygen vacancies formed from Ni-O-Fe chains exhibit lower formation energy (Ef) compared to those from Fe-O-Fe chains in each doping system. Additionally, Ef generally decreases with an increase of Ni content. This Ni-promoted formation of VO is attributed to three factors: weakened Ni-O bonding, the closure of O-2p states to the Fermi level by Ni-O hybridization, and Ni3+ decreasing the positive charges to be compensated by VO formation. Due to these multiple advantages, a modest Ni doping of x = 0.25 can induce a higher PO2 and a lower T comparted to the relatively larger Co doping of x = 0.5, thermodynamically. Kinetically, Ni-doping appears to be a disadvantage as it hinders oxygen migration, due to a higher oxygen migration barrier through SrSrNi compared to the SrSrFe pathway. However, the overall oxygen ion conduction would not be significantly influenced by hopping through a nearby pathway of SrSrFe with a low migration barrier in a system doped with a small amount of Ni. In a word, a small amount of Ni doping has an advantage over Co doping in terms of enhancing the oxygen carrier performance of the parent SrFeO3 system.

Association between Urinary Haloacetic Acid Concentrations and Liver Injury among Women: Results from the Tongji Reproductive and Environmental (TREE) Study.

BACKGROUND: Experimental studies have shown that disinfection byproducts (DBPs) including haloacetic acids (HAAs) can cause liver toxicity, but evidence linking this association in humans is sparse. OBJECTIVES: We aimed to explore the associations between HAA exposures and liver injury. METHODS: We included 922 women between December 2018 and January 2020 from the Tongji Reproductive and Environmental (TREE) cohort study in Wuhan, China. Urinary HAA concentrations including trichloroacetic acid (TCAA) and dichloroacetic acid (DCAA) and serum indicators of liver function, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) were measured. Liver injury was defined as if any of serum indicator levels were above the 90th percentile. Multivariate logistic and linear regression models were fitted to assess the associations of urinary HAA concentrations with the risk of liver injury and liver function indicators. Stratified analyses by age, body mass index (BMI), alcohol use, and passive smoking were also applied to evaluate the potential effect modifiers. RESULTS: There is little evidence of associations of urinary TCAA concentrations with liver injury risk and liver function indicators. However, urinary DCAA concentrations were associated with a higher risk of liver injury [odds ratios (OR) for 1-interquartile range (IQR) increase in natural log (ln) transformed DCAA concentrations: 1.45; 95% confidence interval (CI): 1.07, 1.98]. This association was observed only among nondrinkers (pinteraction=0.058). We also found that a 1-IQR increase in ln-transformed DCAA concentrations was positively associated with ALT levels (percentage change=6.06%; 95% CI: 0.48%, 11.95%) and negatively associated with AST/ALT (percentage change=-4.48%; 95% CI: -7.80%, -1.04%). In addition, urinary DCAA concentrations in relation to higher GGT levels was observed only among passive smokers (pinteraction=0.040). CONCLUSION: Our findings suggest that exposure to DCAA but not TCAA is associated with liver injury among women undergoing assisted reproductive technology. https://doi.org/10.1289/EHP13386.

Effect of different screen brightness and devices on online visual acuity test.

PURPOSE: This study aimed to study the difference in test results of online visual acuity (VA) test under different devices and screen brightness conditions and to compare online VA test with Early Treatment Diabetic Retinopathy Study (ETDRS). METHODS: Healthy volunteers with the best corrected VA of 0.0 LogMAR or higher were recruited. VAs under ETDRS were tested first, and then online VA test (the Stanford Acuity Test, StAT) visual acuities using iPad Air2 and Microsoft Surface pro4 under 50% and 100% screen brightness were performed. The VA results and the testing times were compared between different devices and screen brightness conditions. RESULTS: A total of 101 eyes were included in this study. The VA results measured by the StAT were better than those of ETDRS. The VA results measured at 100% screen brightness were better than those of 50% brightness (mean difference, 0.013 logMAR at most, less than 1 letter); the VA results measured by iPad Air2 were better than those of Surface pro4 (mean difference, -0.009 logMAR at most, less than 1 letter). Significantly less time was spent on VA testing under StAT than that under ETDRS. CONCLUSION: The impact of screen brightness and the device on the VA results generated by online VA tests was clinically insignificant. In addition, online VA tests are found to be reliable and more time efficient than ETDRS.

Avoiding Pitfalls in Adult Spinal Deformity.

To avoid the high rate of complications associated with the surgical management of adult spinal deformity, it is important to recognize and avoid three major pitfalls. The first is patient selection and determining which cases are appropriately indicated. The second is optimizing modifiable medical issues that can lead to a poor outcome, such as smoking, vitamin D deficiency, nutritional status, and poor bone quality. The third is optimizing surgical factors such as defining clinically appropriate, patient-specific target alignment goals as well as using techniques to avoid proximal junctional kyphosis and proximal junctional failure. It is important to describe these three key pitfalls that are commonly seen in the treatment of patients with adult spinal deformity and to describe methods to avoid them.

Effects of air pollution on adverse birth outcomes and pregnancy complications in the U.S. state of Kansas (2000-2015).

Neonatal mortality and morbidity are often caused by preterm birth and lower birth weight. Gestational diabetes mellitus (GDM) and gestational hypertension (GH) are the most prevalent maternal medical complications during pregnancy. However, evidence on effects of air pollution on adverse birth outcomes and pregnancy complications is mixed. Singleton live births conceived between January 1st, 2000, and December 31st, 2015, and reached at least 27 weeks of pregnancy in Kansas were included in the study. Trimester-specific and total pregnancy exposures to nitrogen dioxide (NO2), particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5), and ozone (O3) were estimated using spatiotemporal ensemble models and assigned to maternal residential census tracts. Logistic regression, discrete-time survival, and linear models were applied to assess the associations. After adjustment for demographics and socio-economic status (SES) factors, we found increases in the second and third trimesters and total pregnancy O3 exposures were significantly linked to preterm birth. Exposure to the second and third trimesters O3 was significantly associated with lower birth weight, and exposure to NO2 during the first trimester was linked to an increased risk of GDM. O3 exposures in the first trimester were connected to an elevated risk of GH. We didn't observe consistent associations between adverse pregnancy and birth outcomes with PM2.5 exposure. Our findings indicate there is a positive link between increased O3 exposure during pregnancy and a higher risk of preterm birth, GH, and decreased birth weight. Our work supports limiting population exposure to air pollution, which may lower the likelihood of adverse birth and pregnancy outcomes.

6-Aza-2-Thiothymine-Capped Gold Nanoclusters as Robust Antimicrobial Nanoagents for Eradicating Multidrug-Resistant Escherichia coli Infection.

Multidrug-resistant bacterial infections, especially those caused by multidrug-resistant Escherichia coli (E. coli) bacteria, are an ever-growing threat because of the shrinking arsenal of efficacious antibiotics. Therefore, it is urgently needed to develop a kind of novel, long-term antibacterial agent effectively overcome resistant bacteria. Herein, we present a novel designed antibacterial agent-6-Aza-2-thiothymine-capped gold nanoclusters (ATT-AuNCs), which show excellent antibacterial activity against multidrug-resistant E. coli bacteria. The prepared AuNCs could permeabilize into the bacterial cell membrane via binding with a bivalent cation (e.g., Ca2+), followed by the generation of reactive oxygen species (e.g., •OH and •O2-), ultimately resulting in protein leakage from compromised cell membranes, inducing DNA damage and upregulating pro-oxidative genes intracellular. The AuNCs also speed up the wound healing process without noticeable hemolytic activity or cytotoxicity to erythrocytes and mammalian tissue. Altogether, the results indicate the great promise of ATT-AuNCs for treating multidrug-resistant E. coli bacterial infection.

Combined Anterior Thoracic Vertebral Body Tethering and Posterior Lumbar Tethering Results in Quicker Return to Sport and Activity Compared to Posterior Spinal Instrumented Fusion in Patients with Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: To compare patient-reported physical activity between anterior thoracic vertebral body tethering and posterior lumbar spine tethering (ATVBT/PLST) and posterior spinal instrumentation and fusion (PSIF) with minimum 2 year follow-up. METHODS: Consecutive skeletally immature patients with idiopathic scoliosis and a thoracic and lumbar curve magnitude ≥40° who underwent either ATVBT/PLST or PSIF from 2015-2019 were included. The primary outcome was rate of returning to sport. Secondary outcomes included ability to bend and satisfaction with sport performance as well as weeks until return to sport, school, physical education (PE) classes, and running. RESULTS: Ten patients underwent ATVBT/PLST and 12 underwent PSIF. ATVBT/PLST patients reported significantly faster return to sport (13.5 weeks vs 27.9 weeks, P = .04), running (13.3 weeks vs 28.8 weeks, P = .02), and PE class (12.6 weeks vs 26.2 weeks, P = .04) compared to PSIF patients. ATVBT/PLST patients reported that they had to give up activities due to their ability to bend at lower rates than PSIF patients while reporting "no changes" in their ability to bend after surgery at higher rates than PSIF patients (0% vs 4% giving up activities and 70% vs 0% reporting no changes in bending ability for ATVBT/PLST and PSIF, respectively, P = .01). Compared to PSIF patients, ATVBT/PLST patients experienced less main thoracic and thoracolumbar/lumbar curve correction at most recent follow-up (thoracic: 41 ± 19% vs 69 ± 18%, P = .001; thoracolumbar/lumbar: 59 ± 25% vs 78 ± 15%, P = .02). No significant differences in the number of revision surgeries were observed between ATVBT/PLST and PSIF patients (4 (40%) and 1 (8%) for ATVBT/PLST and PSIF, respectively, P = .221). CONCLUSIONS: ATVBT/PLST patients reported significantly faster rates of returning to sport, running, and PE. In addition, ATVBT/PLST patients were less likely to have to give up activities due to bending ability after surgery and reported no changes in their ability to bend after surgery more frequently than PSIF patients. However, the overall rate of return to the same or higher level of sport participation was high amongst both groups, with no significant difference observed between ATVBT/PLST and PSIF patients.

A deep learning-based semiautomated workflow for triaging follow-up MR scans in treated nasopharyngeal carcinoma.

It is imperative to optimally utilize virtues and obviate defects of fully automated analysis and expert knowledge in new paradigms of healthcare. We present a deep learning-based semiautomated workflow (RAINMAN) with 12,809 follow-up scans among 2,172 patients with treated nasopharyngeal carcinoma from three centers (ChiCTR.org.cn, Chi-CTR2200056595). A boost of diagnostic performance and reduced workload was observed in RAINMAN compared with the original manual interpretations (internal vs. external: sensitivity, 2.5% [p = 0.500] vs. 3.2% [p = 0.031]; specificity, 2.9% [p < 0.001] vs. 0.3% [p = 0.302]; workload reduction, 79.3% vs. 76.2%). The workflow also yielded a triaging performance of 83.6%, with increases of 1.5% in sensitivity (p = 1.000) and 0.6%-1.3% (all p < 0.05) in specificity compared to three radiologists in the reader study. The semiautomated workflow shows its unique superiority in reducing radiologist's workload by eliminating negative scans while retaining the diagnostic performance of radiologists.

BML-111, the agonist of lipoxin A4, suppresses epithelial-mesenchymal transition and migration of MCF-7 cells via regulating the lipoxygenase pathway.

Introduction: Aberrant epithelial-mesenchymal transition (EMT) and migration frequently occur during tumour progression. BML-111, an analogue of lipoxin A4, has been implicated in inflammation in cancer research. Methods: 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, western blot, Reverse Transcription Polymerase Chain Reaction (RT-PCR), transwell assay, immunofluorescence, and immunohistochemistry were conducted in this study. Results: In vitro experiments revealed that BML-111 inhibited EMT and migration in CoCl2-stimulated MCF-7 cells. These effects were achieved by inhibiting MMP-2 and MMP-9, which are downregulated by 5-lipoxygenase (5-LOX). Moreover, BML-111 inhibited EMT and migration of breast cancer cells in BALB/c nude mice inoculated with MCF-7 cells. Conclusion: Our results suggest that BML-111 may be a potential therapeutic drug for breast cancer and that blocking the 5-LOX pathway could be a possible approach for mining effective drug targets.

Carcinosarcoma of the ovary: a case report and literature review.

Objective: Carcinosarcoma of the ovary is a rare pathological type of ovarian cancer that is highly aggressive and occurs most frequently in the female reproductive tract at the site of the uterus. Herein, we explore the clinicopathological features, diagnosis, differential diagnosis, and treatment options for carcinosarcoma of the ovary. Methods: We analyzed the clinical data of a case of carcinosarcoma, observed its histological morphology and immunohistochemical characteristics, detected the homologous recombination repair deficiency gene mutation, and reviewed the relevant literature. Results: A 76-year-old menopausal woman visited our hospital because of abdominal distension, difficulty in urination, and constipation. Ultrasonography demonstrated abnormalities in the uterus and pelvic cavity, suggesting that the patient should undergo surgery. Immunohistochemical findings of carcinosarcoma of the right ovary were as follows: CK fraction (+), vimentin fraction (+), CK5/6 foci (+), p16 (+), p53 in approximately 70% (+), WT-1 foci (+), ER foci (+), PR part (+), Her-2 (1+), CK7 fraction (+), CK20 foci (+), CD99 fraction (+), CD10 fraction (+), CD56 foci (+), c-kit foci (+), SMA part (+), desmin foci (+), PD-L1 (-), SALL4 (-), OCT3/4 (-), p63 (-), p40 (-), D2-40 (-), inhibin (-), PLAP (-), CD30 (-), and Ki67 hotspot in approximately 80% (+). The patient underwent tumor cytoreduction and adjuvant chemotherapy. Currently, she is being followed up for 16 months and has a good general condition. Conclusion: The diagnosis of carcinosarcoma relies on histopathological examination and differentiation of carcinosarcoma from immature teratoma. The current therapeutic regimen for carcinosarcoma is still based on tumor cytoreduction and platinum-containing chemotherapy; research on targeted therapy is still in progress.

Mechanism of DYRK1a in myocardial ischemia-reperfusion injury by regulating ferroptosis of cardiomyocytes.

This study aimed to explore the role and mechanism of DYRK1a regulating ferroptosis of cardiomyocytes during myocardial ischemia-reperfusion injury (MIRI). H9c2 cells treated with oxygen-glucose deprivation/reoxygenation (OGD/R) were used as MIRI cell models and transfected with sh-DYRK1a or/and erastin. Cell viability, apoptosis, and DYRK1a mRNA/protein expression were measured accordingly. The levels of reactive oxygen species (ROS), iron, malondialdehyde (MDA), and glutathione (GSH) were determined. The expression of ferroptosis-related proteins (GPX4, SLC7A11, ACSL4, and TFR1) was detected using western blotting. The MIRI rat model was established to explore the possible role of DYRK1a suppression in cell injury and ferroptosis. OGD/R cells showed elevated mRNA and protein expression for DYRK1a. OGD/R cells transfected with sh-DYRK1a showed elevated cell viability, GSH content, increased GPX4 and SLC7A11 expression, suppressed iron content, MDA, ROS, ACSL4, and TFR1 expression, and reduced apoptosis rate, whereas co-transfection of sh-DYRK1a with erastin reversed the attenuation of sh-DYRK1a on MIRI. The suppressive effect of sh-DYRK1a on MI/R injury was confirmed in an MIRI rat model. DYRK1a mediates ferroptosis of cardiomyocytes to deteriorate MIRI progression.

Role of cancer-associated fibroblasts in colorectal cancer and their potential as therapeutic targets.

Cancer-associated fibroblasts (CAFs) are mesenchymal cells in the tumor microenvironment (TME). CAFs are the most abundant cellular components in the TME of solid tumors. They affect the progression and course of chemotherapy and radiotherapy in various types of tumors including colorectal cancer (CRC). CAFs can promote tumor proliferation, invasion, and metastasis; protect tumor cells from immune surveillance; and resist tumor cell apoptosis caused by chemotherapy, resulting in drug resistance to chemotherapy. In recent years, researchers have become increasingly interested CAF functions and have conducted extensive research. However, compared to other types of malignancies, our understanding of the interaction between CRC cells and CAFs remains limited. Therefore, we searched the relevant literature published in the past 10 years, and reviewed the origin, biological characteristics, heterogeneity, role in the TME, and potential therapeutic targets of CAFs, to aid future research on CAFs and tumors.