Rational design, synthesis and binding mechanisms of novel benzyl geranate derivatives as potential eco-friendly aphid repellents.

BACKGROUND: The push-pull strategy is considered as a promising eco-friendly method for pest management. Plant volatile organic compounds (PVOCs) act as semiochemicals constitute the key factor in implementing this strategy. Benzyl alcohol and geraniol, as functional PVOCs, were reported to regulate insect behavior, showing the potential application in pest control. Using geraniol as lead, a geraniol derivative 5i with fine repellent activity was discovered in our previous work. In order to explore novel, eco-friendly aphid control agents, a series of benzyl geranate derivatives was designed and synthesized using 5i as the lead and benzyl alcohol as the active fragment. RESULTS: Benzyl alcohol was firstly evaluated to have repellent activity to Acyrthosiphon pisum. Based on this repellent fragment, a series of novel benzyl geranate derivatives was rationally designed and synthesized using a scaffold-hopping strategy. Among them, compound T9, with a binding affinity (Kd = 0.43 µm) and a substantial repellency of 64.7% against A. pisum, is the most promising compound. Molecule docking showed that hydrophobic and hydrogen-bonding interactions substantially influenced the binding affinity of compounds with ApisOBP9. Additionally, T9 exhibited low-toxicity to honeybees and ladybugs. CONCLUSION: Using a simple scaffold-hopping strategy combined with active fragment benzyl alcohol, a new derivative T9, with high aphid-repellency and low-toxicity to nontarget organisms, can be considered as a novel potential eco-friendly aphid control agent for sustainable agriculture. © 2023 Society of Chemical Industry.

Hydroxycitric Acid Alleviated Lung Ischemia-Reperfusion Injury by Inhibiting Oxidative Stress and Ferroptosis through the Hif-1α Pathway.

Lung ischemia-reperfusion injury (LIRI) is a prevalent occurrence in various pulmonary diseases and surgical procedures, including lung resections and transplantation. LIRI can result in systemic hypoxemia and multi-organ failure. Hydroxycitric acid (HCA), the primary acid present in the peel of Garcinia cambogia, exhibits anti-inflammatory, antioxidant, and anticancer properties. However, the effects of HCA on LIRI remain unknown. To investigate the impact of HCA on LIRI in mice, the mice were randomly divided into four groups: the control group, the I/R model group, and the I/R + low- or high-dose HCA groups. Human umbilical vein endothelial cells (HUVECs) were subjected to hypoxia for 12 h followed by reoxygenation for 6 h to simulate in vitro LIRI. The results demonstrated that administration of HCA effectively attenuated lung injury, inflammation, and edema induced by ischemia reperfusion. Moreover, HCA treatment significantly reduced malondialdehyde (MDA) and reactive oxygen species (ROS) levels while decreasing iron content and increasing superoxide dismutase (SOD) levels after ischemia-reperfusion insult. Mechanistically, HCA administration significantly inhibited Hif-1α and HO-1 upregulation both in vivo and in vitro. We found that HCA could also alleviate endothelial barrier damage in H/R-induced HUVECs in a concentration-dependent manner. In addition, overexpression of Hif-1α counteracted HCA-mediated inhibition of H/R-induced endothelial cell ferroptosis. In summary, these results indicate that HCA alleviated LIRI by inhibiting oxidative stress and ferroptosis through the Hif-1α pathway.

Molecular and immunological characteristics of patients with CMTM6 low expression colorectal cancer.

CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6), a regulator of programmed cell death ligand 1 (PD-L1), has attracted extensive attention due to its role in tumors. However, research on the expression of CMTM6 in colorectal cancer (CRC) and its relationship with PD-L1 expression and immune cell infiltration is limited. We used The Cancer Genome Atlas database to mine and analyze data from patients with CRC using bioinformatics methods. We investigated the expression of CMTM6 in CRC and its relationship with PD-L1 expression and immune cell infiltration. Immunohistochemistry and PCR were performed to detect CMTM6 and PD-L1 expression in CRC tissues. Differential gene expression analysis was performed using the edgeR package in R and immune cell infiltration analysis was performed using the ssGSEA algorithm. Additionally, GO and KEGG enrichment analyses were conducted to identify the biological processes and pathways associated with low CMTM6 expression. Our study found that CMTM6 expression was significantly upregulated in CRC tissues compared to that in adjacent normal tissues. Patients with high CMTM6 expression exhibited significantly increased levels of PD-L1 expression and higher levels of tumor-infiltrating immune cells compared to patients with low CMTM6 expression. GO and KEGG analyses suggested that CMTM6 may be involved in multiple immune regulatory pathways in CRC.

Multi-scale characterisation of homologous recombination deficiency in breast cancer.

BACKGROUND: Homologous recombination is a robust, broadly error-free mechanism of double-strand break repair, and deficiencies lead to PARP inhibitor sensitivity. Patients displaying homologous recombination deficiency can be identified using 'mutational signatures'. However, these patterns are difficult to reliably infer from exome sequencing. Additionally, as mutational signatures are a historical record of mutagenic processes, this limits their utility in describing the current status of a tumour. METHODS: We apply two methods for characterising homologous recombination deficiency in breast cancer to explore the features and heterogeneity associated with this phenotype. We develop a likelihood-based method which leverages small insertions and deletions for high-confidence classification of homologous recombination deficiency for exome-sequenced breast cancers. We then use multinomial elastic net regression modelling to develop a transcriptional signature of heterogeneous homologous recombination deficiency. This signature is then applied to single-cell RNA-sequenced breast cancer cohorts enabling analysis of homologous recombination deficiency heterogeneity and differential patterns of tumour microenvironment interactivity. RESULTS: We demonstrate that the inclusion of indel events, even at low levels, improves homologous recombination deficiency classification. Whilst BRCA-positive homologous recombination deficient samples display strong similarities to those harbouring BRCA1/2 defects, they appear to deviate in microenvironmental features such as hypoxic signalling. We then present a 228-gene transcriptional signature which simultaneously characterises homologous recombination deficiency and BRCA1/2-defect status, and is associated with PARP inhibitor response. Finally, we show that this signature is applicable to single-cell transcriptomics data and predict that these cells present a distinct milieu of interactions with their microenvironment compared to their homologous recombination proficient counterparts, typified by a decreased cancer cell response to TNFα signalling. CONCLUSIONS: We apply multi-scale approaches to characterise homologous recombination deficiency in breast cancer through the development of mutational and transcriptional signatures. We demonstrate how indels can improve homologous recombination deficiency classification in exome-sequenced breast cancers. Additionally, we demonstrate the heterogeneity of homologous recombination deficiency, especially in relation to BRCA1/2-defect status, and show that indications of this feature can be captured at a single-cell level, enabling further investigations into interactions between DNA repair deficient cells and their tumour microenvironment.

HistoMIL: A Python package for training multiple instance learning models on histopathology slides.

Hematoxylin and eosin (H&E) stained slides are widely used in disease diagnosis. Remarkable advances in deep learning have made it possible to detect complex molecular patterns in these histopathology slides, suggesting automated approaches could help inform pathologists' decisions. Multiple instance learning (MIL) algorithms have shown promise in this context, outperforming transfer learning (TL) methods for various tasks, but their implementation and usage remains complex. We introduce HistoMIL, a Python package designed to streamline the implementation, training and inference process of MIL-based algorithms for computational pathologists and biomedical researchers. It integrates a self-supervised learning module for feature encoding, and a full pipeline encompassing TL and three MIL algorithms: ABMIL, DSMIL, and TransMIL. The PyTorch Lightning framework enables effortless customization and algorithm implementation. We illustrate HistoMIL's capabilities by building predictive models for 2,487 cancer hallmark genes on breast cancer histology slides, achieving AUROC performances of up to 85%.

Dual-energy CT virtual non-calcium: an accurate method for detection of knee osteoarthritis-related edema-like marrow signal intensity.

OBJECTIVES: To evaluate the performance of a dual-energy computed tomography (DECT) virtual non-calcium (VNCa) technique in the detection of edema-like marrow signal intensity (ELMSI) in patients with knee joint osteoarthritis (OA) compared to magnetic resonance imaging (MRI). METHODS: The study received local ethics board approval, and written informed consent was obtained. DECT and MRI were used to examine 28 knees in 24 patients with OA. VNCa images were generated by dual-energy subtraction of calcium. The knee joint was divided into 15 regions for ELMSI grading, performed independently by two musculoskeletal radiologists, with MRI as the reference standard. We also analyzed CT numbers through receiver operating characteristics and calculated cut-off values. RESULTS: For the qualitative analysis, we obtained CT sensitivity (Readers 1, 2 = 83.7%, 89.8%), specificity (Readers 1, 2 = 99.5%, 99.5%), positive predictive value (Readers 1, 2 = 95.3%, 95.7%), and negative predictive value (Readers 1, 2 = 97.9%, 98.7%) for ELMSI. The interobserver agreement was excellent (κ = 0.92). The area under the curve for Reader 1 and Reader 2 was 0.961 (95% CI 0.93, 0.99) and 0.992 (95% CI 0.98, 1.00), respectively. CT numbers obtained from the VNCa images were significantly different between regions with and without ELMSI (p < .001). CONCLUSIONS: VNCa images have good diagnostic performance for the qualitative and quantitative analysis of knee osteoarthritis-related ELMSI.

SP70 is a novel biomarker of hepatocellular carcinoma.

Background: Tumor-specific protein 70 (SP70) was identified as a new biomarker associated with the proliferation and invasion of cancer cells. This study aimed to investigate the expression of SP70 in hepatocellular carcinoma (HCC) and assess its clinical value in the diagnosis and prediction of early HCC recurrence. Methods: A total of 1049 subjects from the First Affiliated Hospital of Nanjing Medical University were recruited in this study. Serum SP70, alpha-fetoprotein (AFP) and prothrombin induced by vitamin K absence II (PIVKA-II) were measured. The diagnostic performance for HCC was obtained using the receiver operating characteristic (ROC) curve, and recurrence-free survival (RFS) was calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify predictive factors of RFS. Results: SP70 was highly expressed in HCC cells and HCC tissue. Serum SP70 levels in the HCC group were significantly higher than in the benign liver diseases group and healthy control group (P<0.001). SP70 combined with AFP showed the best diagnostic performance (AUC=0.909, 95%CI [confidence interval]=0.890-0.929). Kaplan-Meier analysis revealed that patients with high SP70 levels had shorter median RFS than those with low SP70 levels (P=0.003). In addition, high SP70 levels were significantly associated with shorter RFS (P=0.037) in the AFP-negative subgroup. Univariate and multivariate analyses confirmed that preoperative serum SP70 level, serum AFP, tumor diameter and microvascular invasion were independent prognostic factors of RFS. Conclusion: SP70 is a promising biomarker in diagnosing HCC. High preoperative serum SP70 level is associated with an increased risk of early relapse and could be used as a valuable marker to predict early recurrence of HCC after resection.

Engineering amorphous SnO2 nanoparticles integrated into porous N-doped carbon matrix as high-performance anode for lithium-ion batteries.

A facile in-situ preparation strategy is proposed to anchor amorphous SnO2 nanoparticles into the porous N-doped carbon (NC) matrix to fabricate amorphous composite powders (am-SnO2@p-NC), which feature the hierarchically interconnected and well interlaced porous configurations by employing polyvinylpyrrolidone as the soft template. The morphology regulation of the porous structure is precisely realized by adjusting the content of the template and the relationship between structural evolution and electrochemical performance of composite powders is accurately described to explore the optimal template dosage. The results indicate that the am-SnO2@p-NC-50 % composite electrode can deliver the improved lithium storage capacity and cycling performance when the content of the template is controlled at 0.500 g, in which the initial discharge specific capacity is about 1557.6 mAh/g and the reversible value retains at 841.5 mAh/g after 100 cycles at 100 mA/g. Meanwhile, the discharge specific capacity of 869.8 mAh/g is exhibited for the am-SnO2@p-NC-50 % composite electrode after 60 cycles when the current density is recovered from 2000 to 100 mA/g. Moreover, the Li+ ions diffusion coefficient up to about 5.5 × 10-12 cm2/s is calculated from galvanostatic intermittent titration technique tests, which can be partly ascribed to the conductive NC substrate that provides the high electronic conductivity, and partly to the highly porous structure that shortens Li+ ions transfer pathways and guarantees the fast reaction kinetics. Therefore, the hierarchically porous engineering of carbon networks to confine amorphous transition metal oxide nanoparticles is of great significance in the development of high-performance anode materials for lithium-ion batteries.

Aphid-repellent, ladybug-attraction activities, and binding mechanism of methyl salicylate derivatives containing geraniol moiety.

BACKGROUND: Aphids have been mainly controlled by traditional chemical insecticides, resulting in unamiable risk to the environment over the last decades. Push-pull strategy is regarded as a promising eco-friendly approach for aphid management through repelling aphid away and attracting their natural enemy. Methyl salicylate (MeSA), one of typical HIPVs (herbivore-induced plant volatiles), can repel aphids and attract ladybugs. Our previous studies discovered a new lead compound 3e, a salicylate-substituted carboxyl (E)-ß-farnesene derivative that had effective aphid-repellent activity. However, whether 3e has attractive activity to ladybug like MeSA is unknown. Meanwhile, to discover a new derivative for both deterring aphid and recruiting ladybug is meaningful for green control of aphids. RESULTS: Through the structural optimization of 3e, 14 new derivatives were designed and synthesized. Among them, compounds 4e and 4i had good aphid (Acyrthosiphon pisum) repellent activity, and compounds 3e, 4e and 4i had significant ladybug (Harmonia axyridis) attractive activity to males. Particularly, 4i exhibited manifest attractive effect on the females as well. Binding mechanism showed that 4i not only bound effectively with the aphid (Acyrthosiphon pisum) target ApisOBP9 thanks to its multiple hydrophobic interactions and hydrogen-bond, but also had strong binding affinity with ladybug target HaxyOBP15 due to the suitable steric space. Additionally, 4i displayed low toxicity to bee Apis mellifera. CONCLUSION: Compound 3e does exhibit attractive activity to male ladybug as MeSA. However, the new derivative 4i, with both pleasant aphid-repellent and ladybug-attraction activities, can be considered as a novel potential push-pull candidate for aphid control in sustainable agriculture. © 2022 Society of Chemical Industry.

Electrospinning fabrication of Sb-SnSb/TiO2@CNFs composite nanofibers as high-performance anodes for lithium-ion batteries.

The SnSb and TiO2 nanoparticles uniformly embedded into continuous and conductive carbon nanofibers (CNFs) are successfully fabricated through facile electrospinning combined with calcination treatments. The characterization results of the targeted composite nanofibers (Sb-SnSb/TiO2@CNFs-2) confirm that the presence of TiO2 is of significant importance to construct the elaborately designed and intact fiber structure, in which the optimal dosage of the TiO2 precursor is precisely controlled at 2 mmol. Moreover, high theoretical specific capacity of SnSb, available inhibitory effect of TiO2, and great electronic conductivity of CNFs are cooperatively integrated into the Sb-SnSb/TiO2@CNFs-2 composite nanofibers, guaranteeing the enhanced lithium storage capacity and cycling performance when being employed as the anode electrodes. Specifically, the Sb-SnSb/TiO2@CNFs-2 electrode can not only deliver initial discharge specific capacity of 1146.6 mAh/g at 100 mA/g and reversible discharge specific capacity of 580.4 mAh/g after 100 cycles, but also retain discharge specific capacity of 561.3 mAh/g after rate cycles along with recovering the current density to 100 mA/g. Importantly, the Sb-SnSb/TiO2@CNFs-2 electrode is also endowed with prominent advantages in the pseudocapacitive contribution of 66.89 % at 0.8 mV/s. Those investigations and findings of the Sb-SnSb/TiO2@CNFs-2 composite electrodes with facile fabrication process and excellent electrochemical performance can contribute to the practical application of the alloy anodes in the field of the energy storage.

A model based on machine learning for the prediction of cyclosporin A trough concentration in Chinese allo-HSCT patients.

BACKGROUND: Cyclosporin A is a calcineurin inhibitor which has a narrow therapeutic window and high interindividual variability. Various population pharmacokinetic models have been reported; however, professional software and technical personnel were needed and the variables of the models were limited. Therefore, the aim of this study was to establish a model based on machine learning to predict CsA trough concentrations in Chinese allo-HSCT patients. METHODS: A total of 7874 cases of CsA therapeutic drug monitoring data from 2069 allo-HSCT patients were retrospectively included. Sequential forward selection was used to select variable subsets, and eight different algorithms were applied to establish the prediction model. RESULTS: XGBoost exhibited the highest prediction ability. Except for the variables that were identified by previous studies, some rarely reported variables were found, such as norethindrone, WBC, PAB, and hCRP. The prediction accuracy within ±30% of the actual trough concentration was above 0.80, and the predictive ability of the models was demonstrated to be effective in external validation. CONCLUSION: In this study, models based on machine learning technology were established to predict CsA levels 3-4 days in advance during the early inpatient phase after HSCT. A new perspective for CsA clinical application is provided.

Case Report: Persistent left superior vena cava: an incidental finding during peripherally inserted central catheter placement.

Background: A peripherally inserted central catheter (PICC) is a specialized type of long-term intravenous catheter commonly employed for administering chemotherapy. The operation and management of PICC should exclusively be carried out by trained healthcare professionals equipped with the requisite knowledge of anatomy, procedural technique and patient care. Persistent left superior vena cava (PLSVC) is a vascular malformation which is typically asymptomatic in clinical presentation, almost always identified during invasive surgery or imaging examinations. Case presentation: Herein, we detailed a case involving a breast cancer patient whose PLSVC was identified during the placement of PICC because of the negative P-wave in electrocardiogram (ECG). Subsequent examination, including chest x-ray imaging, postoperative enhanced CT of the chest, ECG, and consultation with an experienced imaging physician confirmed that the patient's variant type was PLSVC type I. 2160. Removal of the catheter was deemed unnecessary, as the catheter tip was appropriately positioned and no other concomitant cardiovascular malformations were detected. Conclusion: The PLSVC is a vascular anomaly and is relatively uncommon within the general population. The operator should possess a thorough familiarity with the potential anatomical variations of left superior vena cava, and specialized case profile should be established for patients diagnosed with PLSVC.

Comparison of the prevalence of sarcopenia in geriatric patients in Xining based on three different diagnostic criteria.

BACKGROUND: Sarcopenia is an age-related decline in skeletal muscle mass, which depends on an assessment of muscle strength and muscle mass. The diagnostic definition of sarcopenia varies by region. AIM: To determine the optimal diagnostic criteria for sarcopenia in a plateau population. Cut off values for the components of diagnostic algorithms for sarcopenia in plateau populations should consider altitude. METHODS: One hundred and fifty subjects aged > 60 years attending a tertiary comprehensive hospital in the city of Xining (elevation: 2260 m) between October and December 2018 were enrolled. Handgrip strength, muscle mass, and physical performance were measured. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia (AWGS) 2019 criteria, Beijing criteria, and Lasha criteria. RESULTS: Across diagnostic criteria, there were significant differences in the prevalence of sarcopenia in the overall population and stratified by gender. The prevalence of sarcopenia measured by the AWGS 2019 or Lasha criteria was significantly higher in female compared to male subjects. In males, the prevalence of sarcopenia measured by the Beijing criteria was significantly higher in subjects who identified as Han compared to Minority. In females, there were no significant differences in the prevalence of sarcopenia by ethnicity according to any criteria. CONCLUSION: The Lasha criteria provided a lower prevalence of sarcopenia (males, 8.7%; females, 22.41%; overall, 14%) and were able to differentiate between males and females. The Lasha criteria are likely most appropriate for detection of sarcopenia in this plateau population. We recommend the Lasha criteria for detection of sarcopenia in Xining.

Short-term effect of 0.01% atropine sulphate eye gel on myopia progression in children.

AIM: To investigate the effect of 0.01% atropine sulphate eye gel on myopia progression and axial elongation in a 6-month treatment in children. METHODS: Totally 185 children aged 6-12y with binocular myopia of 3.0 D or less in both eyes were enrolled in this prospective cohort study. The atropine group (n=125) received one drop of 0.01% atropine sulphate eye gel in each eye before bedtime daily. The control group included 60 matched children without drug intervention during the same period. The spherical equivalent and axial length was recorded at baseline and the sixth month of treatment. The efficacy was evaluated by the change of the spherical equivalent and axial length. Adverse events were also recorded. RESULTS: The average spherical equivalent and axial length at baseline were not statistically significant between the atropine group (-1.64±0.80 D, 24.13±0.76 mm) and the control group (-1.59±0.94 D, 24.06±0.77 mm, P>0.05). After 6mo, there was significantly difference in the spherical equivalent progression between the atropine and the control group (-0.27±0.33 vs -0.60±0.35 D, P<0.001), with a relative reduction of 55.0% in myopia progression. The increase in axial elongation in the atropine group was significantly less than control group (0.19±0.14 vs 0.26±0.14 mm, P<0.001), with a relative reduction of 26.9% in axial length. The 84.4% and 38.4% of the eyes progressed by less than 0.50 D and remained stable in the atropine group, compared with 51.7% and 4.2% in the control group. No adverse events were observed. CONCLUSION: Atropine sulphate eye gel 0.01% can slow down myopia progression and axial elongation in children with a 6-month treatment.

Health care worker occupational experiences during the COVID-19 outbreak: A cross-sectional study.

BACKGROUND: Health care workers treating coronavirus disease 2019 (COVID-19) patients experience burnout and stress due to overwork and poor working conditions. AIM: To investigate the work experiences of frontline health care workers in Wuhan city and Qinghai province, China, during the COVID-19 outbreak. METHODS: In this cross-sectional descriptive study, a self-reported questionnaire was designed to evaluate work experiences of medical staff throughout the course of the COVID-19 pandemic. A total of 178 health care workers responded to the questionnaire between February 19 and 29, 2020. Higher questionnaire dimen-sional score confirmed dimensional advantage. RESULTS: Of all dimensions evaluated by this questionnaire, the occupational value dimension had the highest mean score of 2.61 (0.59), followed by the support/security dimension score of 2.30 (0.74). Occupational protection scored lowest at 1.44 (0.75), followed by work environment at 1.97 (0.81). The social relationships dimension had an intermediate score of 2.06 (0.80). Significant differences in working conditions were observed across hospital departments, with the fever ward scoring lowest. Total scores also differed significantly across workplaces; the fever outpatient department scored lowest (P < 0.01). This phenomenon was likely due to the fact that work in the fever outpatient department, where many patients present to hospital, necessitates constant contact with a large number of individuals with insufficient provision of resources (such as protective equipment and social support). Medical workers in the fever outpatient department were burdened with a fear of COVID-19 infection and a lower sense of professional value as compared to workers in other hospital departments. Medical staff in Wuhan worked longer hours (P < 0.01) as compared to elsewhere. The mean support/security dimension score was higher for tertiary hospital as compared to secondary hospital medical staff as well as for Wuhan area as compared to Qinghai region staff (P < 0.01). Staff in Wuhan had a lower mean work environment score as compared to staff in Qinghai (P < 0.05). CONCLUSION: Medical staff treating COVID-19 patients in China report poor occupational experiences strongly affected by work environment, occupational protection and social relationships. Health care managers must address the occupational needs of medical staff by ensuring a supportive and safe work environment.

An Attention-Guided Framework for Explainable Biometric Presentation Attack Detection.

Despite the high performances achieved using deep learning techniques in biometric systems, the inability to rationalise the decisions reached by such approaches is a significant drawback for the usability and security requirements of many applications. For Facial Biometric Presentation Attack Detection (PAD), deep learning approaches can provide good classification results but cannot answer the questions such as "Why did the system make this decision"? To overcome this limitation, an explainable deep neural architecture for Facial Biometric Presentation Attack Detection is introduced in this paper. Both visual and verbal explanations are produced using the saliency maps from a Grad-CAM approach and the gradient from a Long-Short-Term-Memory (LSTM) network with a modified gate function. These explanations have also been used in the proposed framework as additional information to further improve the classification performance. The proposed framework utilises both spatial and temporal information to help the model focus on anomalous visual characteristics that indicate spoofing attacks. The performance of the proposed approach is evaluated using the CASIA-FA, Replay Attack, MSU-MFSD, and HKBU MARs datasets and indicates the effectiveness of the proposed method for improving performance and producing usable explanations.

A Preliminary Study on Self-Healing and Self-Health Management in Older Adults: Perspectives From Healthcare Professionals and Older Adults in Taiwan.

The human body has tremendous self-healing capacity and regeneration after injuries and pathogen invasions. These factors are particularly important in older adults which take longer to heal and recover physically. In addition to clinical investigations, perspectives from both experts in the field and the living experiences of the general public could play significant roles to enhance the body's healing mechanisms in older adults. A semi-structured interview was conducted which included 15 participants (9 experts and 6 older adults aged 65 years and older). Content analysis with an inductive approach was employed about participants' experiences and perspectives. All participants in this study revealed that self-healing mechanisms can be enhanced through physiological, psychological, and socio-environmental factors. When more of these factors can be integrated into a recovery management plan, it can hasten self-healing in older adults. Social capability has a profound impact on an individual's mental health while oral health and hygiene significantly affect the nutritional intake status. In regards to physical aspects, regular daily activity patterns, nutritious eating, moderate exercise, and sleep quality are significant, while psychological aspects such as cheerfulness, positive attitudes, and good interpersonal relationships can help control chronic diseases.

Single serine on TSC2 exerts biased control over mTORC1 activation mediated by ERK1/2 but not Akt.

Tuberous sclerosis complex-2 (TSC2) negatively regulates mammalian target of rapamycin complex 1 (mTORC1), and its activity is reduced by protein kinase B (Akt) and extracellular response kinase (ERK1/2) phosphorylation to activate mTORC1. Serine 1364 (human) on TSC2 bidirectionally modifies mTORC1 activation by pathological growth factors or hemodynamic stress but has no impact on resting activity. We now show this modification biases to ERK1/2 but not Akt-dependent TSC2-mTORC1 activation. Endothelin-1-stimulated mTORC1 requires ERK1/2 activation and is bidirectionally modified by phospho-mimetic (S1364E) or phospho-silenced (S1364A) mutations. However, mTORC1 activation by Akt-dependent stimuli (insulin or PDGF) is unaltered by S1364 modification. Thrombin stimulates both pathways, yet only the ERK1/2 component is modulated by S1364. S1364 also has negligible impact on mTORC1 regulation by energy or nutrient status. In vivo, diet-induced obesity, diabetes, and fatty liver couple to Akt activation and are also unaltered by TSC2 S1364 mutations. This contrasts to prior reports showing a marked impact of both on pathological pressure-stress. Thus, S1364 provides ERK1/2-selective mTORC1 control and a genetic means to modify pathological versus physiological mTOR stimuli.

Optical coherence tomography: evaluating the effects of stent boost subtract imaging on stent underexpansion in STEMI patients.

BACKGROUND: To evaluate the effect of stent boost subtract (SBS) imaging on stent underexpansion during percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) by optical coherence tomography (OCT). METHODS: One hundred thirty-eight STEMI patients who underwent drug-eluting stent (DES) implantation were prospectively recruited and divided into the SBS group (69 cases) and the CAG group (69 cases) according to whether SBS was used to guide PCI. Finally, OCT was performed on all enrolled patients, and the OCT results were used as the gold standard to evaluate the impact of standard SBS technology on stent underexpansion immediately after DES implantation. RESULTS: SBS identified 51 patients (24%) with stent underexpansion while OCT identified 56 patients (27.2%). SBS has a sensitivity of 80%, a specificity of 96%, a positive predictive value of 88%, and a negative predictive value of 93% for identifying stent underexpansion. CONCLUSION: Compared with OCT, SBS technology is a rapid stent imaging evaluation method that can accurately quantify the stent expansion level and is time-saving and economical.