ITGB5 facilitates gastric cancer metastasis by promoting TGFBR2 endosomal recycling.

TGFBR2, a key regulator of the TGFß signaling pathway, plays a crucial role in gastric cancer (GC) metastasis through its endosomal recycling process. Despite its importance, the mechanisms governing this process remain unclear. Here, we identify integrin ß5 (ITGB5) as a critical mediator that promotes TGFBR2 endosomal recycling. Our study reveals elevated expression of ITGB5 in GC, particularly in metastatic cases, correlating with poor patient outcomes. Knockdown of ITGB5 impairs GC cell metastasis both in vitro and in vivo. Mechanistically, ITGB5 facilitates epithelial-mesenchymal transition mediated by TGFß signaling, thereby enhancing GC metastasis. Acting as a scaffold, ITGB5 interacts with TGFBR2 and SNX17, facilitating SNX17-mediated endosomal recycling of TGFBR2 and preventing lysosomal degradation, thereby maintaining its surface distribution on tumor cells. Notably, TGFß signaling directly upregulates ITGB5 expression, establishing a positive feedback loop that exacerbates GC metastasis. Our findings shed light on the role of ITGB5 in promoting GC metastasis through SNX17-mediated endosomal recycling of TGFBR2, providing insights for the development of targeted cancer therapies.

Intercalated and Surface-Adsorbed Phosphate Anions in NiFe Layered Double-Hydroxide Catalysts Synergistically Enhancing Oxygen Evolution Reaction Activity.

The oxygen evolution reaction (OER), a crucial semireaction in water electrolysis and rechargeable metal-air batteries, is vital for carbon neutrality. Hindered by a slow proton-coupled electron transfer, an efficient catalyst activating the formation of an O-H bond is essential. Here, we proposed a straightforward one-step hydrothermal procedure for fabricating PO43--modified NiFe layered double-hydroxide (NiFe LDH) catalysts and investigated the role of PO43- anions in enhancing OER. Phosphate amounts can efficiently regulate LDH morphology, crystallinity, composition, and electronic configuration. The optimized sample showed a low overpotential of 267 mV at 10 mA cm-2. Density functional theory calculations revealed that intercalated and surface-adsorbed PO43- anions in NiFe LDH reduced the Gibbs free energy in the rate-determining step of *OOH formation, balancing oxygen-containing intermediate adsorption/dissociation and promoting the OER. Intercalated phosphate ions accelerated precatalyst dehydrogenation kinetics, leading to a rapid reconstruction into active NiFe oxyhydroxide species. Surface-adsorbed PO43- interacted favorably with adsorbed *OOH on the active Ni sites, stabilizing *OOH. Overall, the synergistic effects of intercalated and surface-adsorbed PO43- anions significantly contributed to enhanced OER activity. Achieving optimal catalytic activity requires a delicate equilibrium between thermodynamic and kinetic factors by meticulously regulating the quantity of introduced PO43- ions. This endeavor will facilitate a deeper comprehension of the influence of anions in electrocatalysis for OER.

Effects of olfactory and/or gustatory stimuli on feeding of preterm infants: A systematic review and meta-analysis.

AIM: To evaluate the effect of olfactory and/or gustatory stimulation interventions on feeding outcomes in preterm infants. METHODS: We conducted systematic searches across various academic databases, including PubMed, Embase, Web of Science, the Cochrane Library, the Chinese Biomedical Literature Service System, China National Knowledge Infrastructure, the Wanfang Database, and the Wipu Database. These searches aimed to identify randomized controlled trials investigating the impact of olfactory and/or gustatory stimulation on preterm infants. The search period spanned from the inception of the databases until December 2022. Two independent evaluators autonomously reviewed the literature, extracted pertinent data, assessed the quality of the included studies, and conducted a meta-analysis using RevMan 5.3 software. RESULTS: A total of 7 randomized controlled trials or quasi-experimental studies were included, with a total of 871 participants. Olfactory and gustatory stimulation demonstrated a reduction in the time to full enteral feeds in preterm infants when compared to usual care (MD = -1.60 days; 95% CI = -2.31, -0.89; p<0.0001). No substantial evidence was identified regarding the influence of olfactory and gustatory stimulation on the duration of gastric tube placement, length of hospitalization, incidence of necrotizing enterocolitis, or occurrence of spontaneous bowel perforation in preterm infants. CONCLUSIONS: Olfactory and gustatory stimulation show potential benefits for preterm infants. However, due to the low to very low level of certainty associated with the available data, our ability to assess the effects is limited. Further trials and studies are essential to enhance our understanding of the mechanisms and effectiveness of olfactory and gustatory stimulation therapies.

Therapeutic effects of treat and repair strategy in pediatric patients with pulmonary arterial hypertension and simple congenital heart defects.

Surgical indications for patients with pulmonary arterial hypertension (PAH) and congenital heart defects are controversial. The treat and repair strategy has demonstrated efficacy in adult populations, but there have been no studies on pediatric patients. This study included pediatric patients with PAH and simple congenital heart defects who underwent corrective repair between 2012 and 2021. According to the preoperative treatment strategies, the patients were divided into a regular strategy group (Group 1) and a treat-and-repair strategy group (Group 2). Postoperative recovery and follow-up results were compared between the two groups. A total of 33 patients were included in this study. Group 1 consisted of 19 patients, whereas Group 2 consisted of 14 patients. The pulmonary vascular resistance index in Group 2 was higher than that in Group 1 (10.9 ± 4.1 vs. 8.2 ± 1.6 WU, p = 0.031). There were no differences in postoperative recovery between the two groups (p > 0.05). During follow-up, five patients were lost (three in Group 1 and two in Group 2). The median follow-up period was 59 months. One patient died in Group 1, and two patients died in Group 2. There was no significant difference in the survival curve (p = 0.39). At the last follow-up, another seven patients had experienced a non-low-risk condition, with a total of three non-low-risk patients in Group 1 and seven in Group 2, including one patient in each group who had a history of ICU admission. According to the ROC curve, a preoperative PVRi <8.2 WU×m2 can predict postoperative persistent low-risk state, PVRi <5.2 WU×m2 can avoid postoperative death and/or ICU administration. In pediatric patients with PAH and simple congenital heart defects, the treat and repair strategies may provide surgery opportunities, PVRi should be <8 WU×m2, and <5.2 WU×m2 is the best choice.

A longitudinal electrophysiological and behavior dataset for PD rat in response to deep brain stimulation.

Here we presented an electrophysiological dataset collected from layer V of the primary motor cortex (M1) and the corresponding behavior dataset from normal and hemi-parkinson rats over 5 consecutive weeks. The electrophysiological dataset was constituted by the raw wideband signal, neuronal spikes, and local field potential (LFP) signal. The open-field test was done and recorded to evaluate the behavior variation of rats among the entire experimental cycle. We conducted technical validation of this dataset through sorting the spike data to form action potential waveforms and analyzing the spectral power of LFP data, then based on these findings a closed-loop DBS protocol was developed by the oscillation activity response of M1 LFP signal. Additionally, this protocol was applied to the hemi-parkinson rat for five consecutive days while simultaneously recording the electrophysiological data. This dataset is currently the only publicly available dataset that includes longitudinal closed-loop DBS recordings, which can be utilized to investigate variations of neuronal activity within the M1 following long-term closed-loop DBS, and explore additional reliable biomarkers.

FpPEX5 and FpPEX7 are involved in the growth, reproduction, DON toxin production, and pathogenicity in Fusarium pseudograminearum.

Fusarium crown rot, caused by Fusarium pseudograminearum, is a devastating disease affecting the yield and quality of cereal crops. Peroxisomes are single-membrane organelles that play a critical role in various biological processes in eukaryotic cells. To functionally characterise peroxisome biosynthetic receptor proteins FpPEX5 and FpPEX7 in F. pseudograminearum, we constructed deletion mutants, ΔFpPEX5 and ΔFpPEX7, and complementary strains, ΔFpPEX5-C and ΔFpPEX7-C, and analysed the functions of FpPEX5 and FpPEX7 proteins using various phenotypic observations. The deletion of FpPEX5 and FpPEX7 resulted in a significant deficiency in mycelial growth and conidiation and blocked the peroxisomal targeting signal 1 and peroxisomal targeting signal 2 pathways, which are involved in peroxisomal matrix protein transport, increasing the accumulation of lipid droplets and reactive oxygen species. The deletion of FpPEX5 and FpPEX7 may reduce the formation of toxigenic bodies and decrease the pathogenicity of F. pseudograminearum. These results indicate that FpPEX5 and FpPEX7 play vital roles in the growth, asexual reproduction, virulence, and fatty acid utilisation of F. pseudograminearum. This study provides a theoretical basis for controlling stem rot in wheat.

Sex-Specific Association Between Childhood Adversity and Accelerated Biological Aging.

Is childhood adversity associated with biological aging, and if so, does sex modify the association, and do lifestyle and mental health mediate the association? A lifespan analysis is conducted using data on 142 872 participants from the UK Biobank to address these questions. Childhood adversity is assessed through the online mental health questionnaire (2016), including physical neglect, physical abuse, emotional neglect, emotional abuse, sexual abuse, and a cumulative score. Biological aging is indicated by telomere length (TL) measured from leukocyte DNA using qPCR, and the shorter TL indicates accelerated biological aging; a lifestyle score is constructed using body mass index, physical activity, drinking, smoking, and diet; mental disorder is assessed using depression, anxiety, and insomnia at the baseline survey. The results reveal a sex-specific association such that childhood adversity is associated with shorter TL in women after adjusting for covariates including polygenic risk score for TL, but not in men. Unhealthy lifestyle and mental disorder partially mediate the association in women. The proportions of indirect effects are largest for sexual and physical abuse. These findings highlight the importance of behavioral and psychological interventions in promoting healthy aging among women who experienced childhood adversity, particularly sexual and physical abuse.

Nosocomial Infections After Pediatric Congenital Heart Disease Surgery: Data from National Center for Cardiovascular Diseases in China.

Purpose: Infection prevention and control (IPC) has a significant impact on the prognosis after pediatric cardiac surgery. This study aimed to provide surveillance data on the incidence and density of various infections during the COVID-19 epidemic and explore the influence of multi-drug resistant organisms (MDRO) on in-hospital prognosis after congenital heart disease surgery. Methods: This single-center retrospective study included pediatric patients who underwent cardiac surgery between 2021 and 2022. The results of the postoperative bacterial and fungal cultures and antimicrobial stewardship were collected. The demographic characteristics (age and weight), operation-related parameters (RACHS-1 grade, duration of cardiopulmonary bypass, and aortic cross clamp), and surgical outcomes (extracorporeal membrane oxygenation, delayed sternal closure, mortality, duration of mechanical ventilation, length of intensive care unit stay and hospital stay, and hospitalization costs) of MDRO and non-MDRO patients were compared. Results: A total of 4776 patients were included. There were 101 infectious culture results after the operation, with a nosocomial infection rate of 2.1%. There were 40 MDRO specimens from 36 patients, 50 non-MDRO specimens from 30 patients, and 11 fungal specimens from 10 patients. The incidence of pneumonia was 1.5%, with a ventilator-associated pneumonia incidence density of 7.2/1000 patient-days. The incidence of sepsis was 0.4%, with a catheter-related bloodstream infection incidence density of 0.24/ 1000 patient-days. The incidence density of catheter-associated tract infection was 0.45/ 1000 patient-days. The incidence of surgical site infection was 0.06%. The culture proportion before commencing antibiotics was 93% and the antibiotic consumption intensity was 30.7 DDD/100 bed-days. The length of intensive care unit stay in MDRO infection patients increased compared with that in non-MDRO infection patients, 30 (18,52) vs 17 (7,62) days, p=0.05). Conclusion: The IPC performance of Fuwai Hospital achieved satisfactory results. MDRO infection can lead to prolonged intensive care unit stay.

Developed countries have advanced infection prevention and control systems and comprehensive postoperative infection monitoring data for congenital heart disease. While developing countries have initiated efforts in infection prevention and control, global attention remains substantial. This study aimed to provide comprehensive infection surveillance data and identify possible implementation for further improvement in the National Center for Cardiovascular Diseases in China (Fuwai Hospital). This was a retrospective single-center study. We included pediatric patients who underwent cardiac surgery at a pediatric surgical center between 2021 and 2022, with an age limit of 14 years. Exclusion criteria included patients undergoing medical therapy, interventional therapy, or surgical therapy in other centers in Fuwai Hospital. This study, for the first time, reports the incidence of comprehensive healthcare-associated infection surveillance and targeted surveillance (encompassing device-associated infection, surgical site infection, and multi-drug resistant organisms) after pediatric cardiac surgery at the National Center for Cardiovascular Diseases in China. In addition, we report the data on antimicrobial stewardship. We compared the surgical outcome and hospitalization costs between patients with multi-drug resistant organism infection and those without multi-drug resistant organism infection and found that multi-drug resistant organism infection can lead to prolonged intensive care unit length of stay. The Fuwai Hospital achieved satisfactory infection prevention and control results. However, because China is a large developing country exhibiting notable variations in medical conditions across its diverse regions, prospective, multicenter, observational studies should be carried out for future research based on existing evidence.

Remodeling ceramide homeostasis promotes functional maturation of human pluripotent stem cell-derived ß cells.

Human pluripotent stem cell-derived ß cells (hPSC-ß cells) show the potential to restore euglycemia. However, the immature functionality of hPSC-ß cells has limited their efficacy in application. Here, by deciphering the continuous maturation process of hPSC-ß cells post transplantation via single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), we show that functional maturation of hPSC-ß cells is an orderly multistep process during which cells sequentially undergo metabolic adaption, removal of negative regulators of cell function, and establishment of a more specialized transcriptome and epigenome. Importantly, remodeling lipid metabolism, especially downregulating the metabolic activity of ceramides, the central hub of sphingolipid metabolism, is critical for ß cell maturation. Limiting intracellular accumulation of ceramides in hPSC-ß cells remarkably enhanced their function, as indicated by improvements in insulin processing and glucose-stimulated insulin secretion. In summary, our findings provide insights into the maturation of human pancreatic ß cells and highlight the importance of ceramide homeostasis in function acquisition.

Hepatitis C viremic lung transplantation to aviremic recipients: Comprehensive outcomes and post-transplant viremia.

BACKGROUND/AIMS: Direct-acting antiviral (DAA) therapy has revolutionized solid organ transplantation by providing an opportunity to utilize organs from HCV-viremic donors. Though transplantation of HCV-viremic donor organs into aviremic recipients is safe in the short term, midterm data on survival and post-transplant complications is lacking. We provide a midterm assessment of complications of lung transplantation (LT) up to 2 years post-transplant, including patient and graft survival between HCV-viremic transplantation (D+) and HCV-aviremic transplantation (D-). METHODS: This is a retrospective cohort study including 500 patients from 2018 to 2022 who underwent LT at our quaternary care institution. Outcomes of patients receiving D+ grafts were compared to those receiving D- grafts. Recipients of HCV antibody+ but PCR- grafts were treated as D- recipients. RESULTS: We identified 470 D- and 30 D+ patients meeting inclusion criteria. Crude mortality did not differ between groups (p = .43). Patient survival at years 1 and 2 did not differ between D+ and D- patients (p = .89, p = .87, respectively), and graft survival at years 1 and 2 did not differ between the two groups (p = .90, p = .88, respectively). No extrahepatic manifestations or fibrosing cholestatic hepatitis (FCH) occurred among D+ recipients. D+ and D- patients had similar rates of post-transplant chronic lung allograft rejection (CLAD) (p = 6.7% vs. 12.8%, p = .3), acute cellular rejection (60.0% vs. 58.0%, p = .8) and antibody-mediated rejection (16.7% vs. 14.2%, p = .7). CONCLUSION: There is no difference in midterm patient or graft survival between D+ and D-LT. No extrahepatic manifestations of HCV occurred. No differences in any type of rejection including CLAD were observed, though follow-up for CLAD was limited. These results provide additional support for the use of HCV-viremic organs in selected recipients in LT.

Experimental and theoretical studies on the compatibility of DNTF and typical hydrocarbon polymer binders.

3,4-bis(3-nitrofurazan-4-yl) furoxan (DNTF) is one of the third-generation energetic compounds with excellent comprehensive properties, which can be added to polymer bonded explosive (PBX) to improve energy levels and regulate sensitivity, so the compatibility of DNTF with other components in PBX, especially the binder, is the first question. Herein, two typical hydrocarbon polymers commonly used in PBX, which are hydroxyl-terminated polybutadiene (HTPB) and polyisobutylene (PIB), were selected as the binder, and the compatibility of HTPB and PIB with DNTF was investigated by differential scanning calorimetry (DSC), the vacuum stability test (VST), and in situ infrared spectroscopy (in situ IR). The results of compatibility experiments were verified by using the binding energy and solubility parameter criteria in molecular dynamics (MD). Experimental and MD simulation results showed that DNTF could be compatible with PIB but incompatible with HTPB. The frontier molecular orbital theory in quantum chemistry (QC) was adopted to explore the frontier orbital electron distribution and energy levels of DNTF/HTPB and DNTF/PIB composite systems to better understand the microscopic compatibility mechanism. The compatibility results of the two composite systems were explained from the perspective of electron transfer. All these can deduce that a hydrocarbon polymer binder with a saturated carbon-hydrogen bond at the end of the molecular chain has good compatibility with DNTF, compared with a hydroxyl group, which has bad compatibility with DNTF.

The influences of Yellow River input and nutrient dynamics on colloidal Fe migration in the Bohai Sea, China.

The coupling relationship between the <1 kDa, 1-3 kDa, 3-10 kDa, 10-100 kDa, and 100 kDa-0.45 µm Fe fractions and the environmental factors in the Bohai Sea (BS) was investigated. The 1-100 kDa Fe in the surface water exhibited a non-conservative phenomenon during the river-sea mixing process, which was related to the removal of colloidal Fe via flocculation during this process. For the bottom water, the ligands released by the sediments may form additions to the <100 kDa Fe. The COC and DOC were mainly closely related to the behavior of the Fe in the bottom water. The <1 and 3-10 kDa Fe was mainly significantly positively correlated with the DOC, while the <100 kDa-0.45 µm Fe was significantly negatively correlated with the DOC. <100 kDa LMW colloidal Fe exhibited more synergistic behavior with easily absorbed ammonium salts.

Bacillus sp. alone or combined with salicylic acid inhibited Trichoderma spp. infection on harvested white Hypsizygus marmoreus.

Introduction: White Hypsizygus marmoreus is a popular edible mushroom. It is rich in nutrition and flavor but vulnerable to fungal disease, resulting in nutrient loss and aging. Methods: In this study, the pathogenic fungus Trichoderma spp. BBP-6 and its antagonist Bacillus sp. 1-23 were isolated and identified. The negative effects caused by this pathogen were judged by detecting a series of changes in the infected white H. marmoreus. The effects of Bacillus sp. 1-23 on Trichoderma spp. BBP-6 and the infected white H. marmoreus were detected. The effect of Bacillus sp. 1-23 treatment combined with salicylic acid (SA) was also considered. Results: The results showed that Trichoderma spp. BBP-6 could affect the activities of antioxidant enzymes PAL, POD, CAT, SOD, GR, PPO, and APX to interfere with the stability of the white H. marmoreus antioxidant enzyme system and cause the mushroom severe browning and nutrition loss, as well as general quality deterioration. Bacillus sp. 1-23 could produce chitinase and chitosanase enzymes to inhibit Trichoderma spp. BBP-6 directly. SA reinforced this inhibitory. Bacillus sp. 1-23 alone or combined with SA could help white H. marmoreus from the Trichoderma spp. BBP-6 infection to effectively maintain nutrients, restore and stabilize the antioxidant system, and reduce the production of malondialdehyde, superoxide anion and hydrogen peroxide. Discussion: Thus, such treatments could be considered potential methods to alleviate damage from disease and extend the shelf life of white H. marmoreus.

Comparison of fungal vs bacterial infections in the medical intensive liver unit: Cause or corollary for high mortality?

BACKGROUND: Due to development of an immune-dysregulated phenotype, advanced liver disease in all forms predisposes patients to sepsis acquisition, including by opportunistic pathogens such as fungi. Little data exists on fungal infection within a medical intensive liver unit (MILU), particularly in relation to acute on chronic liver failure. AIM: To investigate the impact of fungal infections among critically ill patients with advanced liver disease, and compare outcomes to those of patients with bacterial infections. METHODS: From our prospective registry of MILU patients from 2018-2022, we included 27 patients with culture-positive fungal infections and 183 with bacterial infections. We compared outcomes between patients admitted to the MILU with fungal infections to bacterial counterparts. Data was extracted through chart review. RESULTS: All fungal infections were due to Candida species, and were most frequently blood isolates. Mortality among patients with fungal infections was significantly worse relative to the bacterial cohort (93% vs 52%, P < 0.001). The majority of the fungal cohort developed grade 2 or 3 acute on chronic liver failure (ACLF) (90% vs 64%, P = 0.02). Patients in the fungal cohort had increased use of vasopressors (96% vs 70%, P = 0.04), mechanical ventilation (96% vs 65%, P < 0.001), and dialysis due to acute kidney injury (78% vs 52%, P = 0.014). On MILU admission, the fungal cohort had significantly higher Acute Physiology and Chronic Health Evaluation (108 vs 91, P = 0.003), Acute Physiology Score (86 vs 65, P = 0.003), and Model for End-Stage Liver Disease-Sodium scores (86 vs 65, P = 0.041). There was no significant difference in the rate of central line use preceding culture (52% vs 40%, P = 0.2). Patients with fungal infection had higher rate of transplant hold placement, and lower rates of transplant; however, differences did not achieve statistical significance. CONCLUSION: Mortality was worse among patients with fungal infections, likely attributable to severe ACLF development. Prospective studies examining empiric antifungals in severe ACLF and associations between fungal infections and transplant outcomes are critical.

Assessing recent recurrence after hepatectomy for hepatitis B-related hepatocellular carcinoma by a predictive model based on sarcopenia.

BACKGROUND: Sarcopenia may be associated with hepatocellular carcinoma (HCC) following hepatectomy. But traditional single clinical variables are still insufficient to predict recurrence. We still lack effective prediction models for recent recurrence (time to recurrence < 2 years) after hepatectomy for HCC. AIM: To establish an interventable prediction model to estimate recurrence-free survival (RFS) after hepatectomy for HCC based on sarcopenia. METHODS: We retrospectively analyzed 283 hepatitis B-related HCC patients who underwent curative hepatectomy for the first time, and the skeletal muscle index at the third lumbar spine was measured by preoperative computed tomography. 94 of these patients were enrolled for external validation. Cox multivariate analysis was per-formed to identify the risk factors of postoperative recurrence in training cohort. A nomogram model was developed to predict the RFS of HCC patients, and its predictive performance was validated. The predictive efficacy of this model was evaluated using the receiver operating characteristic curve. RESULTS: Multivariate analysis showed that sarcopenia [Hazard ratio(HR) = 1.767, 95%CI: 1.166-2.678, P < 0.05], alpha-fetoprotein ≥ 40 ng/mL (HR = 1.984, 95%CI: 1.307-3.011, P < 0.05), the maximum diameter of tumor > 5 cm (HR = 2.222, 95%CI: 1.285-3.842, P < 0.05), and hepatitis B virus DNA level ≥ 2000 IU/mL (HR = 2.1, 95%CI: 1.407-3.135, P < 0.05) were independent risk factors associated with postoperative recurrence of HCC. Based on the sarcopenia to assess the RFS model of hepatectomy with hepatitis B-related liver cancer disease (SAMD) was established combined with other the above risk factors. The area under the curve of the SAMD model was 0.782 (95%CI: 0.705-0.858) in the training cohort (sensitivity 81%, specificity 63%) and 0.773 (95%CI: 0.707-0.838) in the validation cohort. Besides, a SAMD score ≥ 110 was better to distinguish the high-risk group of postoperative recurrence of HCC. CONCLUSION: Sarcopenia is associated with recent recurrence after hepatectomy for hepatitis B-related HCC. A nutritional status-based prediction model is first established for postoperative recurrence of hepatitis B-related HCC, which is superior to other models and contributes to prognosis prediction.

Better clinical outcomes and return to sport rates with additional medial meniscus root tear repair in high tibial osteotomy for medial compartmental knee osteoarthritis.

PURPOSE: This retrospective study aimed to investigate whether the repair of medial meniscus posterior root tears (MMPRTs) is effective for improving clinical outcomes and return to sports rates in young patients (50 years old or younger) with medial compartment knee osteoarthritis (KOA) and MMPRTs. METHODS: Between 2016 and 2019, 153 patients with KOA and MMPRTs who underwent open-wedge high tibial osteotomy (OWHTO) were retrospectively included. The patients were divided into OWHTO combined with MMPRT repair (n = 73) and isolated OWHTO (n = 80) groups. Lysholm scores, Hospital for Special Surgery (HHS) scores, Tegner scores, flexion contracture, range of knee flexion, return to sports rates and postoperative complications were compared. Radiological outcomes, including hip-knee-ankle angle (HKA), medial proximal tibial angle (MPTA), joint line convergence angle (JLCA) and Kellgren-Lawrence (K-L) grade, were compared between the two groups. RESULTS: After a mean follow-up of 30.1 ± 3.0 months, the OWHTO + Repair group observed better clinical outcomes compared with the OWHTO group (Lysholm score: 86.7 ± 7.4 vs. 81.6 ± 6.9, p = 0.023. HHS score: 85.4 ± 8.20 vs. 80.5 ± 7.1, p = 0.039). The OWHTO + Repair group had higher Tegner scores and return to sports rates than the OWHTO group (Tegner score: 6 vs. 5, p = 0.020; return to sports rates: 38% vs. 15%, p = 0.001). No fracture or major complications occurred. Radiological outcomes showed no significant differences between the two groups (HKA: 181.1 ± 2.7 vs. 180.1 ± 1.5 n.s; MPTA: 90.1 ± 1.8 vs. 89.2 ± 1.4, n.s; JLCA:1.9 ± 0.7 vs. 2.1 ± 0.7, n.s). CONCLUSIONS: Additional MMPRT repair during OWHTO was associated with better clinical outcomes and higher rates of return to sports in young patients with medial compartment KOA and MMPRTs. LEVEL OF EVIDENCE: Level III.

Cardiac MRI-Enriched Phenomapping Classification and Differential Treatment Outcomes in Patients With Ischemic Cardiomyopathy.

BACKGROUND: Significant controversy continues to confound patient selection and referral for revascularization and mitral valve intervention in patients with ischemic cardiomyopathy (ICM). Cardiac magnetic resonance (CMR) enables comprehensive phenotyping with gold-standard tissue characterization and volumetric/functional measures. Therefore, we sought to determine the impact of CMR-enriched phenomapping patients with ICM to identify differential outcomes following surgical revascularization and surgical mitral valve intervention (sMVi). METHODS: Consecutive patients with ICM referred for CMR between 2002 and 2017 were evaluated. Latent class analysis was performed to identify phenotypes enriched by comprehensive CMR assessment. The primary end point was death, heart transplant, or left ventricular assist device implantation. A multivariable Cox survival model was developed to determine the association of phenogroups with overall survival. Subgroup analysis was performed to assess the presence of differential response to post-magnetic resonance imaging procedural interventions. RESULTS: A total of 787 patients were evaluated (63.0±11.2 years, 24.8% women), with 464 primary events. Subsequent surgical revascularization and sMVi occurred in 380 (48.3%) and 157 (19.9%) patients, respectively. Latent class analysis identified 3 distinct clusters of patients, which demonstrated significant differences in overall outcome (P<0.001). Latent class analysis identified differential survival benefit of revascularization in patients as well as patients who underwent revascularization with sMVi, based on phenogroup classification, with phenogroup 3 deriving the most survival benefit from revascularization and revascularization with sMVi (hazard ratio, 0.61 [0.43-0.88]; P=0.0081). CONCLUSIONS: CMR-enriched unsupervised phenomapping identified distinct phenogroups, which were associated with significant differential survival benefit following surgical revascularization and sMVi in patients with ICM. Phenomapping provides a novel approach for patient selection, which may enable personalized therapeutic decision-making for patients with ICM.

Protein Corona-Mediated Inhibition of Nanozyme Activity: Impact of Protein Shape.

During biomedical applications, nanozymes, exhibiting enzyme-like characteristics, inevitably come into contact with biological fluids in living systems, leading to the formation of a protein corona on their surface. Although it is acknowledged that molecular adsorption can influence the catalytic activity of nanozymes, there is a dearth of understanding regarding the impact of the protein corona on nanozyme activity and its determinant factors. In order to address this gap, we employed the AuNR@Pt@PDDAC [PDDAC, poly(diallyldimethylammonium chloride)] nanorod (NR) as a model nanozyme with multiple activities, including peroxidase, oxidase, and catalase-mimetic activities, to investigate the inhibitory effects of the protein corona on the catalytic activity. After the identification of major components in the plasma protein corona on the NR, we observed that spherical proteins and fibrous proteins induced distinct inhibitory effects on the catalytic activity of nanozymes. To elucidate the underlying mechanism, we uncovered that the adsorbed proteins assembled on the surface of the nanozymes, forming protein networks (PNs). Notably, the PNs derived from fibrous proteins exhibited a screen mesh-like structure with smaller pore sizes compared to those formed by spherical proteins. This structural disparity resulted in a reduced efficiency for the permeation of substrate molecules, leading to a more robust inhibition in activity. These findings underscore the significance of the protein shape as a crucial factor influencing nanozyme activity. This revelation provides valuable insights for the rational design and application of nanozymes in the biomedical fields.

Association of 8-hydroxy-2'-deoxyguanosine with motoric cognitive risk in elderly Chinese people: RUGAO longevity and aging cross-sectional study.

BACKGROUND: Motor cognitive risk syndrome (MCR) represents a critical pre-dementia and disability state characterized by a combination of objectively measured slow walking speed and subjective memory complaints (SMCs). This study aims to identify risk factors for MCR and investigate the relationship between plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and MCR among Chinese community-dwelling elderly populations. METHODS: A total of 1312 participants were involved in this study based on the data of the Rugao Longevity and Aging Study (RuLAS). The MCR was characterized by SMCs and slow walking speed. The SCCs were defined as a positive answer to the question 'Do you feel you have more problems with memory than most?' in a 15-item Geriatric Depression Scale. Slow walking speed was determined by one standard deviation or more below the mean value of the patient's age and gender group. The plasma of 8-OHdG were measured by a technician in the biochemistry laboratory of the Rugao People's Hospital during the morning of the survey. RESULTS: The prevalence of MCR was found to be 7.9%. After adjusting for covariates, significant associations with MCR were observed in older age (OR 1.057; p = 0.018), history of cerebrovascular disease (OR 2.155; p = 0.010), and elevated 8-OHdG levels (OR 1.007; p = 0.003). CONCLUSIONS: This study indicated the elevated plasma 8-OHdG is significantly associated with increased MCR risk in the elderly, suggesting its potential as a biomarker for early detection and intervention in MCR. This finding underscores the importance of monitoring oxidative DNA damage markers in predicting cognitive and motor function declines, offering new avenues for research and preventive strategies in aging populations.