mTORC1 Signaling in Brain Endothelial Progenitors Contributes to CCM Pathogenesis.

BACKGROUND: Cerebral vascular malformations (CCMs) are primarily found within the brain, where they result in increased risk for stroke, seizures, and focal neurological deficits. The unique feature of the brain vasculature is the blood-brain barrier formed by the brain neurovascular unit. Recent studies suggest that loss of CCM genes causes disruptions of blood-brain barrier integrity as the inciting events for CCM development. CCM lesions are proposed to be initially derived from a single clonal expansion of a subset of angiogenic venous capillary endothelial cells (ECs) and respective resident endothelial progenitor cells (EPCs). However, the critical signaling events in the subclass of brain ECs/EPCs for CCM lesion initiation and progression are unclear. METHODS: Brain EC-specific CCM3-deficient (Pdcd10BECKO) mice were generated by crossing Pdcd10fl/fl mice with Mfsd2a-CreERT2 mice. Single-cell RNA-sequencing analyses were performed by the chromium single-cell platform (10× genomics). Cell clusters were annotated into EC subtypes based on visual inspection and GO analyses. Cerebral vessels were visualized by 2-photon in vivo imaging and tissue immunofluorescence analyses. Regulation of mTOR (mechanistic target of rapamycin) signaling by CCM3 and Cav1 (caveolin-1) was performed by cell biology and biochemical approaches. RESULTS: Single-cell RNA-sequencing analyses from P10 Pdcd10BECKO mice harboring visible CCM lesions identified upregulated CCM lesion signature and mitotic EC clusters but decreased blood-brain barrier-associated EC clusters. However, a unique EPC cluster with high expression levels of stem cell markers enriched with mTOR signaling was identified from early stages of the P6 Pdcd10BECKO brain. Indeed, mTOR signaling was upregulated in both mouse and human CCM lesions. Genetic deficiency of Raptor (regulatory-associated protein of mTOR), but not of Rictor (rapamycin-insensitive companion of mTOR), prevented CCM lesion formation in the Pdcd10BECKO model. Importantly, the mTORC1 (mTOR complex 1) pharmacological inhibitor rapamycin suppressed EPC proliferation and ameliorated CCM pathogenesis in Pdcd10BECKO mice. Mechanistic studies suggested that Cav1/caveolae increased in CCM3-depleted EPC-mediated intracellular trafficking and complex formation of the mTORC1 signaling proteins. CONCLUSIONS: CCM3 is critical for maintaining blood-brain barrier integrity and CCM3 loss-induced mTORC1 signaling in brain EPCs initiates and facilitates CCM pathogenesis.

Clinical features in antiglycine receptor antibody-related disease: a case report and update literature review.

Background and objectives: Antiglycine receptor (anti-GlyR) antibody mediates multiple immune-related diseases. This study aimed to summarize the clinical features to enhance our understanding of anti-GlyR antibody-related disease. Methods: By collecting clinical information from admitted patients positive for glycine receptor (GlyR) antibody, the clinical characteristics of a new patient positive for GlyR antibody were reported in this study. To obtain additional information regarding anti-GlyR antibody-linked illness, clinical data and findings on both newly reported instances in this study and previously published cases were merged and analyzed. Results: A new case of anti-GlyR antibody-related progressive encephalomyelitis with rigidity and myoclonus (PERM) was identified in this study. A 20-year-old man with only positive cerebrospinal fluid anti-GlyR antibody had a good prognosis with first-line immunotherapy. The literature review indicated that the common clinical manifestations of anti-GlyR antibody-related disease included PERM or stiff-person syndrome (SPS) (n = 179, 50.1%), epileptic seizure (n = 94, 26.3%), and other neurological disorders (n = 84, 24.5%). Other neurological issues included demyelination, inflammation, cerebellar ataxia and movement disorders, encephalitis, acute psychosis, cognitive impairment or dementia, celiac disease, Parkinson's disease, neuropathic pain and allodynia, steroid-responsive deafness, hemiballism/tics, laryngeal dystonia, and generalized weakness included respiratory muscles. The group of PERM/SPS exhibited a better response to immunotherapy than others. Conclusions: The findings suggest the presence of multiple clinical phenotypes in anti-GlyR antibody-related disease. Common clinical phenotypes include PERM, SPS, epileptic seizure, and paraneoplastic disease. Patients with RERM/SPS respond well to immunotherapy.

Selective Tumor Inhibition Effect of Drug-Free Layered Double Hydroxide-Based Films via Responding to Acidic Microenvironment.

Nickel-titanium alloy stents are widely used in the interventional treatment of various malignant tumors, and it is important to develop nickel-titanium alloy stents with selective cancer-inhibiting and antibacterial functions to avoid malignant obstruction caused by tumor invasion and bacterial colonization. In this work, an acid-responsive layered double hydroxide (LDH) film was constructed on the surface of a nickel-titanium alloy by hydrothermal treatment. The release of nickel ions from the film in the acidic tumor microenvironment induces an intracellular oxidative stress response that leads to cell death. In addition, the specific surface area of LDH nanosheets could be further regulated by heat treatment to modulate the release of nickel ions in the acidic microenvironment, allowing the antitumor effect to be further enhanced. This acid-responsive LDH film also shows a good antibacterial effect against S. aureus and E. coli. Besides, the LDH film prepared without the introduction of additional elements maintains low toxicity to normal cells in a normal physiological environment. This work offers some guidance for the design of a practical nickel-titanium alloy stent for the interventional treatment of tumors.

Effectiveness and safety of brucea javanica oil assisted TACE versus TACE in the treatment of liver cancer: a systematic review and meta-analysis of randomized controlled trials.

Background: The effectiveness and safety of using Brucea javanica oil (BJO) in combination with Transarterial Chemoembolization (TACE) for liver cancer treatment are subjects of debate. This study aims to assess the comparative effectiveness and safety of BJO-assisted TACE versus TACE alone and quantifies the differences between these two treatment methods. Methods: A systematic search was conducted in multiple databases including PubMed, Cochrane, CNKI, and Wanfang, until 1 July 2023. Meta-analysis was conducted, and the results were presented as mean difference (MD), risk ratio (RR), and 95% confidence intervals (CI). Results: The search yielded 11 RCTs, with a combined sample size of 1054 patients. Meta-analysis revealed that BJO-assisted TACE exhibited superior outcomes compared to standalone TACE. Specific data revealed that BJO-assisted TACE improves clinical benefit rate by 22% [RR = 1.22, 95% CI (1.15, 1.30)], increases the number of people with improved quality of life by 32%, resulting in an average score improvement of 9.53 points [RR = 1.32, 95% CI (1.22, 1.43); MD = 9.53, 95% CI (6.95, 12.10)]. Furthermore, AFP improvement rate improved significantly by approximately 134% [RR = 2.34, 95% CI (1.58, 3.46)], accompanied by notable improvements in liver function indicators, with an average reduction of 27.19 U/L in AST [MD = -27.19, 95% CI (-40.36, -14.02)], 20.77 U/L in ALT [MD = -20.77, 95% CI (-39.46, -2.08)], 12.17 µmol/L in TBIL [MD = -12.17, 95% CI (-19.38, -4.97)], and a decrease of 43.72 pg/mL in VEGF [MD = -43.72, 95% CI (-63.29, -24.15)]. Most importantly, there was a 29% reduction in the occurrence of adverse reactions [RR = 0.71, 95% CI (0.60, 0.84)]. Conclusion: These findings indicate that BJO-assisted TACE may be considered as a potentially beneficial treatment option for liver cancer patients when compared to standalone TACE. It appears to contribute to improved treatment outcomes, enhanced quality of life, and potentially reduced adverse reactions, suggesting it warrants further investigation as a promising approach for liver cancer treatment. Systematic Review Registration: identifier CRD42023428948.

NIR-triggered arsenic-loaded layered double hydroxide-based films for localized thermal synergistic chemotherapy.

Portal vein tumor thrombus (PVTT) formed by cancer cell invasion is a major cause of high mortality in hepatocellular carcinoma (HCC), and the formation of thrombus will be accelerated by bacterial colonization on the surface of the implant after surgery. In this work, Polypyrrole-coated arsenic-loaded layered double hydroxide films were in situ constructed on the nickel-titanium alloy for the efficient killing of tumour cells by thermo-therapeutic synergistic chemotherapy. The good near-infrared photothermal conversion ability of polypyrrole enables the sample surface temperature to be raised to about 51 °C at a low photothermal power (0.5 w/cm2), while the elevated temperature could further accelerate the release of drug arsenic. In addition, when NIR light is not applied, the polypyrrole coating also cleverly acts as a "barrier layer" to reduce the natural release of arsenic in normal tissues to avoid toxicity issues. In vivo and in vitro experiments have demonstrated that the platform exhibits excellent antitumor and antibacterial abilities. In contrast to the systemic toxicity issues associated with systemic circulation of nanotherapeutic drugs, this in situ functional film is expected to be used in localised interventions for precise drug delivery, and is also more suitable for surgical treatment scenarios in PVTT surgeries.

The effects of high-intensity interval training/moderate-intensity continuous training on the inhibition of fat accumulation in rats fed a high-fat diet during training and detraining.

BACKGROUND: Compared with moderate-intensity continuous training (MICT), high-intensity interval training (HIIT) has at least a comparable effect on inhibiting an increase in fat. However, few studies have been conducted to examine the effects of detraining on body fat in rats fed a high-fat diet. The present study aimed to compare the effects of 10 weeks of HIIT or MICT as well as 6 weeks of detraining on body fat in rats fed a high-fat diet. METHODS: After being fed a high-fat diet for 8 weeks, 54 female rats were randomly assigned to six groups: (1) CON-10, sedentary control for 10 weeks; (2) MICT-10, 10 weeks of MICT; (3) HIIT-10, 10 weeks of HIIT; (4) CON-16, sedentary control for 16 weeks; (5) MICT-16, 10 weeks of MICT followed by 6 weeks of training cessation; and (6) HIIT-16, 10 weeks of HIIT followed by 6 weeks of training cessation. The training was performed 5 days/week. The subcutaneous adipose tissue (inguinal; SCAT), visceral adipose tissue (periuterine; VAT) and serum lipid profile were analysed after 10 or 16 weeks. Adipose tissue triglyceride lipase (ATGL) protein expression in VAT was assessed by western blotting. RESULTS: HIIT-10 and MICT-10 prevented the increase in SCAT, VAT and serum lipid levels seen in the CON group. During the 6-week detraining period, HIIT continued to prevent the increase in adipose tissue mass observed in the CON group, whereas MICT at least maintained this inhibition. The inhibition of fat mass increase was mainly the result of preventing adipocyte hypertrophy. The HIIT-10 and HIIT-16 groups showed the highest ATGL protein expression. CONCLUSIONS: HIIT has a comparable effect to MICT on inhibiting fat accumulation in female rats; however, the inhibition of SCAT and VAT increase by HIIT is superior to MICT after short-term training cessation.

PP2Ac Regulates Autophagy via Mediating mTORC1 and ULK1 During Osteoclastogenesis in the Subchondral Bone of Osteoarthritis.

The molecular mechanism underlying abnormal osteoclastogenesis triggering subchondral bone remodeling in osteoarthritis (OA) is still unclear. Here, single-cell and bulk transcriptomics sequencing analyses are performed on GEO datasets to identify key molecules and validate them using knee joint tissues from OA patients and rat OA models. It is found that the catalytic subunit of protein phosphatase 2A (PP2Ac) is highly expressed during osteoclastogenesis in the early stage of OA and is correlated with autophagy. Knockdown or inhibition of PP2Ac weakened autophagy during osteoclastogenesis. Furthermore, the ULK1 expression of the downstream genes is significantly increased when PP2Ac is knocked down. PP2Ac-mediated autophagy is dependent on ULK1 phosphorylation activity during osteoclastogenesis, which is associated with enhanced dephosphorylation of ULK1 Ser637 residue regulating at the post-translational level. Additionally, mTORC1 inhibition facilitated the expression level of PP2Ac during osteoclastogenesis. In animal OA models, decreasing the expression of PP2Ac ameliorated early OA progression. The findings suggest that PP2Ac is also a promising therapeutic target in early OA.

Microstructure and Mechanical Properties of Multilayered Ti-Based Bulk Metallic Glass Composites Containing Various Thicknesses of Ti-Rich Laminates.

In order to optimize the balance between strength and toughness, a series of multilayered Ti-based bulk metallic glass composites (BMGCs) with varying thicknesses of Ti-rich layers were successfully fabricated. The findings reveal that with an increase in the thickness of the Ti-rich layers, both the flexural yield strength and ultimate strength decreased from 2066 MPa and 2717 MPa to 668 MPa and 1163 MPa, respectively. Conversely, there was a noticeable increase in flexural strain. The fracture toughness of these multilayered Ti-based BMGCs decreased as the thickness of the Ti-rich layers increased; nevertheless, it stabilized at approximately 80 MPa·m1/2 when the thickness reached 100 µm. It was observed that a shift in the dominant deformation mode may be accountable for this phenomenon. These noteworthy characteristics suggest that adjusting the thickness of Ti-rich layers in multilayered BMGCs can effectively optimize mechanical performance, shedding light on the manufacturing of novel BMGCs with high performance.

Development and validation of a clinical predictive model for high-volume lymph node metastasis of papillary thyroid carcinoma.

The central lymph node metastasis (CLNM) status in the cervical region serves as a pivotal determinant for the extent of surgical intervention and prognosis in papillary thyroid carcinoma (PTC). This paper seeks to devise and validate a predictive model based on clinical parameters for the early anticipation of high-volume CLNM (hv-CLNM, > 5 nodes) in high-risk patients. A retrospective analysis of the pathological and clinical data of patients with PTC who underwent surgical treatment at Medical Centers A and B was conducted. The data from Center A was randomly divided into training and validation sets in an 8:2 ratio, with those from Center B serving as the test set. Multifactor logistic regression was harnessed in the training set to select variables and construct a predictive model. The generalization ability of the model was assessed in the validation and test sets. The model was evaluated through the receiver operating characteristic area under the curve (AUC) to predict the efficiency of hv-CLNM. The goodness of fit of the model was examined via the Brier verification technique. The incidence of hv-CLNM in 5897 PTC patients attained 4.8%. The occurrence rates in males and females were 9.4% (128/1365) and 3.4% (156/4532), respectively. Multifactor logistic regression unraveled male gender (OR = 2.17, p < .001), multifocality (OR = 4.06, p < .001), and lesion size (OR = 1.08 per increase of 1 mm, p < .001) as risk factors, while age emerged as a protective factor (OR = 0.95 per an increase of 1 year, p < .001). The model constructed with four predictive variables within the training set exhibited an AUC of 0.847 ([95%CI] 0.815-0.878). In the validation and test sets, the AUCs were 0.831 (0.783-0.879) and 0.845 (0.789-0.901), respectively, with Brier scores of 0.037, 0.041, and 0.056. Subgroup analysis unveiled AUCs for the prediction model in PTC lesion size groups (≤ 10 mm and > 10 mm) as 0.803 (0.757-0.85) and 0.747 (0.709-0.785), age groups (≤ 31 years and > 31 years) as 0.778 (0.720-0.881) and 0.837 (0.806-0.867), multifocal and solitary cases as 0.803 (0.767-0.838) and 0.809 (0.769-0.849), and Hashimoto's thyroiditis (HT) and non-HT cases as 0.845 (0.793-0.897) and 0.845 (0.819-0.871). Male gender, multifocality, and larger lesion size are risk factors for hv-CLNM in PTC patients, whereas age serves as a protective factor. The clinical predictive model developed in this research facilitates the early identification of high-risk patients for hv-CLNM, thereby assisting physicians in more efficacious risk stratification management for PTC patients.

Prediction of dose distributions for non-small cell lung cancer patients using MHA-ResUNet.

BACKGROUND: The current level of automation in the production of radiotherapy plans for lung cancer patients is relatively low. With the development of artificial intelligence, it has become a reality to use neural networks to predict dose distributions and provide assistance for radiation therapy planning. However, due to the significant individual variability in the distribution of non-small cell lung cancer (NSCLC) planning target volume (PTV) and the complex spatial relationships between the PTV and organs at risk (OARs), there is still a lack of a high-precision dose prediction network tailored to the characteristics of NSCLC. PURPOSE: To assist in the development of volumetric modulated arc therapy (VMAT) plans for non-small cell lung cancer patients, a deep neural network is proposed to predict high-precision dose distribution. METHODS: This study has developed a network called MHA-ResUNet, which combines a large-kernel dilated convolution module and multi-head attention (MHA) modules. The network was trained based on 80 VMAT plans of NSCLC patients. CT images, PTV, and OARs were fed into the independent input channel. The dose distribution was taken as the output to train the model. The performance of this network was compared with that of several commonly used networks, and the networks' performance was evaluated based on the voxel-level mean absolute error (MAE) within the PTV and OARs, as well as the error in clinical dose-volume metrics. RESULTS: The MAE between the predicted dose distribution and the manually planned dose distribution within the PTV is 1.43 Gy, and the D95 error is less than 1 Gy. Compared with the other three commonly used networks, the dose error of the MHA-ResUNet is the smallest in PTV and OARs. CONCLUSIONS: The proposed MHA-ResUNet network improves the receptive field and filters the shallow features to learn the relative spatial relation between the PTV and the OARs, enabling accurate prediction of dose distributions in NSCLC patients undergoing VMAT radiotherapy.

Life's essential 8, genetic susceptibility, and incident cardiac arrhythmias: a population-based prospective cohort study.

BACKGROUND: Ideal cardiovascular health (CVH) has been associated with reduced cardiovascular disease risk and mortality, but its association with cardiac arrhythmias were still unsettled. In this prospective cohort study, we investigated the relationship between CVH and subsequent arrhythmias risk, including atrial fibrillation/flutter (AF), ventricular arrhythmias, and bradyarrhythmias. METHODS: Data from 287,264 participants initially free of arrhythmias in the UK Biobank were included in the analysis. Cox regression models were used to examine the relationship between CVH levels calculated by the American Heart Association's Life's Essential 8 (LE8) metrics, with cardiac arrhythmias risk. RESULTS: During a median follow-up period of 12.8 years, 16,802 incident AF, 2186 incident ventricular arrhythmias, and 4128 incident bradyarrhythmias were identified. After adjustment for confounding factors, participants with high initial CVH levels had a significantly lower risk for AF (HR 0.63, 95% CI 0.59-0.68), ventricular arrhythmias (HR 0.48, 95% CI 0.40-0.59), and bradyarrhythmias (HR 0.64, 95% CI 0.55-0.74) compared to those with low CVH levels. Furthermore, each SD increase in LE8 scores was associated with a 15% lower risk of AF, 21% for ventricular arrhythmias, and 13% for bradyarrhythmias, respectively. Additionally, a significant interaction was observed between CVH levels and the genetic risk of AF (P for interaction, 0.021). The reverse correlation seemed to be more noticeable in individuals with a lower genetic susceptibility to AF. CONCLUSIONS: We concluded that higher levels of CVH, estimated by the LE8 metrics, were associated with significantly reduced risks of AF, ventricular arrhythmias, and bradyarrhythmias.

MoRgs3 functions in intracellular reactive oxygen species perception-integrated cAMP signaling to promote appressorium formation in Magnaporthe oryzae.

Regulator of G-protein signaling (RGS) proteins exhibit GTPase-accelerating protein activities to govern G-protein function. In the rice blast fungus Magnaporthe oryzae, there is a family of at least eight RGS and RGS-like proteins (MoRgs1 to MoRgs8), each exhibiting distinct or shared functions in the growth, appressorium formation, and pathogenicity. MoRgs3 recently emerged as one of the crucial regulators that senses intracellular oxidation during appressorium formation. To explore this unique regulatory mechanism of MoRgs3, we identified the nucleoside diphosphate kinase MoNdk1 that interacts with MoRgs3. MoNdk1 phosphorylates MoRgs3 under induced intracellular reactive oxygen species levels, and MoRgs3 phosphorylation is required for appressorium formation and pathogenicity. In addition, we showed that MoRgs3 phosphorylation determines its interaction with MoCrn1, a coronin-like actin-binding protein homolog, which regulates MoRgs3 internalization. Finally, we provided evidence demonstrating that MoRgs3 functions in MoMagA-mediated cAMP signaling to regulate normal appressorium induction. By revealing a novel signal perception mechanism, our studies highlighted the complexity of regulation during the appressorium function and pathogenicity of the blast fungus. IMPORTANCE: We report that MoRgs3 becomes phosphorylated in an oxidative intracellular environment during the appressorium formation stage. We found that this phosphorylation is carried out by MoNdk1, a nucleoside diphosphate kinase. In addition, this phosphorylation leads to a higher binding affinity between MoRgs3 and MoCrn1, a coronin-like actin-binding protein that was implicated in the endocytic transport of several other RGS proteins of Magnaporthe oryzae. We further found that the internalization of MoRgs3 is indispensable for its GTPase-activating protein function toward the Gα subunit MoMagA. Importantly, we characterized how such cellular regulatory events coincide with cAMP signaling-regulated appressorium formation and pathogenicity in the blast fungus. Our studies uncovered a novel intracellular reactive oxygen species signal-transducing mechanism in a model pathogenic fungus with important basic and applied implications.

Inhibitor of cardiolipin biosynthesis-related enzyme MoGep4 confers broad-spectrum anti-fungal activity.

Plant pathogens cause devastating diseases, leading to serious losses to agriculture. Mechanistic understanding of pathogenesis of plant pathogens lays the foundation for the development of fungicides for disease control. Mitophagy, a specific form of autophagy, is important for fungal virulence. The role of cardiolipin, mitochondrial signature phospholipid, in mitophagy and pathogenesis is largely unknown in plant pathogenic fungi. The functions of enzymes involved in cardiolipin biosynthesis and relevant inhibitors were assessed using a set of assays, including genetic deletion, plant infection, lipidomics, chemical-protein interaction, chemical inhibition, and field trials. Our results showed that the cardiolipin biosynthesis-related gene MoGEP4 of the rice blast fungus Magnaporthe oryzae regulates growth, conidiation, cardiolipin biosynthesis, and virulence. Mechanistically, MoGep4 regulated mitophagy and Mps1-MAPK phosphorylation, which are required for virulence. Chemical alexidine dihydrochloride (AXD) inhibited the enzyme activity of MoGep4, cardiolipin biosynthesis and mitophagy. Importantly, AXD efficiently inhibited the growth of 10 plant pathogens and controlled rice blast and Fusarium head blight in the field. Our study demonstrated that MoGep4 regulates mitophagy, Mps1 phosphorylation and pathogenesis in M. oryzae. In addition, we found that the MoGep4 inhibitor, AXD, displays broad-spectrum antifungal activity and is a promising candidate for fungicide development.

[Effects of water-nitrogen interactions on NH3 and N2O emissions and yield in winter wheat cropland]. / 水氮互作对冬小麦农田NH3和N2O排放及产量的影响.

To investigate the effects of different irrigation and nitrogen application modes on nitrogen gaseous loss in winter wheat farmland, we conducted a field experiment at Changqing Irrigation Experiment Station in Shandong Province, with two irrigation levels (80%-90% θf(I1) and 70%-80% θf(I2)) and three nitrogen application levels (conventional nitrogen application of 240 kg·hm-2(N1), nitrogen reduction of 12.5% (N2), and nitrogen reduction of 25% (N3)). The results showed that ammonia volatilization and nitrous oxide emission rate peak appeared within 2-4 days after fertilization or irrigation. The ammonia volatilization rate during the chasing fertilizer period was significantly higher than that during the basal fertilizer period. Compared with other treatments, the ave-rage ammonia volatilization rate of I2N2 treatment during the chasing fertilizer period was reduced by 10.1%-51.6%, and the average nitrous oxide emission rate over the whole growth period was reduced by 15.4%-52.2%. The ammonia volatilization rate was significantly positively associated with surface soil pH value and ammonium nitrogen content, while the nitrous oxide emission rate was significantly positively associated with nitrate content in topsoil. The accumulation amount of soil ammonia volatilization and nitrous oxide emission ranged from 0.83-1.42 and 0.11-0.33 kg·hm-2, respectively. Moderate reduction of irrigation water and nitrogen input could effectively reduce cumulative amounts of ammonia volatilization and nitrous oxide emission from winter wheat farmland. The cumulative amounts of ammonia volatilization and nitrous oxide emission under I1N3 and I2N2 treatments were signi-ficantly lower than those under other treatments. The highest winter wheat yield (5615.6 kg·hm-2) appeared in I2N2 treatment. The irrigation water utilization efficiency of I2 was significantly higher than that of I1, with the maximum increase rate of 45.2%. Compared with N1 and N3 treatments, the maximum increase rate of nitrogen fertilizer productivity and agricultural utilization efficiency in N2 reached 15.2% and 31.8%, respectively. In conclusion, the treatment with 70%-80% θf irrigation level and 210 kg·hm-2 nitrogen input could effectively improve the utilization efficiency of irrigation water and nitrogen fertilization and reduce gaseous loss from winter wheat farmland.

Unveiling the Stacking Fault-Driven Phase Transition Delaying Cryogenic Fracture in Fe-Co-Cr-Ni-Mo-C-Based Medium-Entropy Alloy.

In this work, the tensile deformation mechanisms of the Fe55Co17.5Cr12.5Ni10Mo5-xCx-based medium-entropy alloy at room temperature (R.T.), 77 K, and 4.2 K are studied. The formation of micro-defects and martensitic transformation to delay the cryogenic fracture are observed. The results show that FeCoCrNiMo5-xCx-based alloys exhibit outstanding mechanical properties under cryogenic conditions. Under an R.T. condition, the primary contributing mechanism of strain hardening is twinning-induced plasticity (TWIP), whereas at 77 K and 4.2 K, the activation of martensitic transformation-induced plasticity (TRIP) becomes the main strengthening mechanism during cryogenic tensile deformation. Additionally, the carbide precipitation along with increased dislocation density can significantly improve yield and tensile strength. Furthermore, the marked reduction in stacking fault energy (SFE) at cryogenic temperatures can promote mechanisms such as twinning and martensitic transformations, which are pivotal for enhancing ductility under extreme conditions. The Mo4C1 alloy obtains the optimal strength-ductility combination at cryogenic-to-room temperatures. The tensile strength and elongation of the Mo4C1 alloy are 776 MPa and 50.5% at R.T., 1418 MPa and 71.2% in liquid nitrogen 77 K, 1670 MPa and 80.0% in liquid helium 4.2 K, respectively.

Quasi-1D Conductive Network Composites for Ultra-Sensitive Strain Sensing.

Highly performance flexible strain sensor is a crucial component for wearable devices, human-machine interfaces, and e-skins. However, the sensitivity of the strain sensor is highly limited by the strain range for large destruction of the conductive network. Here the quasi-1D conductive network (QCN) is proposed for the design of an ultra-sensitive strain sensor. The orientation of the conductive particles can effectively reduce the number of redundant percolative pathways in the conductive composites. The maximum sensitivity will reach the upper limit when the whole composite remains only "one" percolation pathway. Besides, the QCN structure can also confine the tunnel electron spread through the rigid inclusions which significantly enlarges the strain-resistance effect along the tensile direction. The strain sensor exhibits state-of-art performance including large gauge factor (862227), fast response time (24 ms), good durability (cycled 1000 times), and multi-mechanical sensing ability (compression, bending, shearing, air flow vibration, etc.). Finally, the QCN sensor can be exploited to realize the human-machine interface (HMI) application of acoustic signal recognition (instrument calibration) and spectrum restoration (voice parsing).

Aging and Autophagy: Roles in Musculoskeletal System Injury.

Aging is a multifactorial process that ultimately leads to a decline in physiological function and a consequent reduction in the health span, and quality of life in elderly population. In musculoskeletal diseases, aging is often associated with a gradual loss of skeletal muscle mass and strength, resulting in reduced functional capacity and an increased risk of chronic metabolic diseases, leading to impaired function and increased mortality. Autophagy is a highly conserved physiological process by which cells, under the regulation of autophagy-related genes, degrade their own organelles and large molecules by lysosomal degradation. This process is unique to eukaryotic cells and is a strict regulator of homeostasis, the maintenance of energy and substance balance. Autophagy plays an important role in a wide range of physiological and pathological processes such as cell homeostasis, aging, immunity, tumorigenesis and neurodegenerative diseases. On the one hand, under mild stress conditions, autophagy mediates the restoration of homeostasis and proliferation, reduction of the rate of aging and delay of the aging process. On the other hand, under more intense stress conditions, an inadequate suppression of autophagy can lead to cellular aging. Conversely, autophagy activity decreases during aging. Due to the interrelationship between aging and autophagy, limited literature exists on this topic. Therefore, the objective of this review is to summarize the current concepts on aging and autophagy in the musculoskeletal system. The aim is to better understand the mechanisms of age-related changes in bone, joint and muscle, as well as the interaction relationship between autophagy and aging. Its goal is to provide a comprehensive perspective for the improvement of diseases of the musculoskeletal system.

Serum IGFBP5 as a predictor of major adverse cardiac events in patients with acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) is a serious condition with high mortality rates. Early risk stratification is of significant importance to assess the prognosis. Insulin-like growth factor-binding protein 5 (IGFBP5) levels in AMI patients and its potential as a prognosis biomarker were unclear. OBJECTIVE: To investigate serum IGFBP5 levels in AMI and its prognostic value for short-term major adverse cardiovascular events (MACE). METHODS: We collected serum IGFBP5 levels from 200 patients with new-onset AMI and 71 coronary heart disease (CAD) patients without AMI. Linear regression was used to analyze the relationship between IGFBP5 and baseline variables. AMI patients were followed up, and the risk of major adverse cardiovascular events (MACE) was assessed using Kaplan-Meier curve, multivariate Cox models and restricted cubic spline (RCS) analysis. RESULTS: During a median follow-up of 217 days, 40 patients developed MACE. Serum IGFBP5 was associated with serum cardiac troponin T (cTnT) and C-reactive protein (CRP) (P = 0.013 and P = 0.013). In multivariable survival analyses, higher IGFBP5 was associated with an increased risk of MACE [HR = 1.183, 95%CI (1.104, 1.268), P < 0.001)]. There was a positive and linear association between IGFBP5 levels and the occurrence of MACE (P for nonlinearity = 0.283). The positive association between IGFBP5 and MACE risk consist across subgroups characterized by demographics and comorbidities. CONCLUSION: Serum IGFBP5 was highly expressed in patients with AMI and positively associated with the short-term risk of MACE. Circulating IGFBP5 may be a diagnostic and prognostic indicator for AMI, and further studies with larger sample and longer follow-up are warranted.

Trends in cardiovascular risk factor prevalence, treatment, and control among US adolescents aged 12 to 19 years, 2001 to March 2020.

BACKGROUND: Early-life cardiovascular risk factors (CVRFs) are known to be associated with target organ damage during adolescence and premature cardiovascular morbidity and mortality during adulthood. However, contemporary data describing whether the prevalence of CVRFs and treatment and control rates have changed are limited. This study aimed to examine the temporal trends in the prevalence, treatment, and control of CVRFs among US adolescents over the past 2 decades. METHODS: This is a serial cross-sectional study using data from nine National Health and Nutrition Examination Survey cycles (January 2001-March 2020). US adolescents (aged 12 to 19 years) with information regarding CVRFs (including hypertension, elevated blood pressure [BP], diabetes, prediabetes, hyperlipidemia, obesity, overweight, cigarette use, inactive physical activity, and poor diet quality) were included. Age-adjusted trends in CVRF prevalence, treatment, and control were examined. Joinpoint regression analysis was performed to estimate changes in the prevalence, treatment, and control over time. The variation by sociodemographic characteristics were also described. RESULTS: A total of 15,155 US adolescents aged 12 to 19 years (representing ≈ 32.4 million people) were included. From 2001 to March 2020, there was an increase in the prevalence of prediabetes (from 12.5% [95% confidence interval (CI), 10.2%-14.9%] to 37.6% [95% CI, 29.1%-46.2%]) and overweight/obesity (from 21.1% [95% CI, 19.3%-22.8%] to 24.8% [95% CI, 21.4%-28.2%]; from 16.0% [95% CI, 14.1%-17.9%] to 20.3% [95% CI, 17.9%-22.7%]; respectively), no improvement in the prevalence of elevated BP (from 10.4% [95% CI, 8.9%-11.8%] to 11.0% [95% CI, 8.7%-13.4%]), diabetes (from 0.7% [95% CI, 0.2%-1.2%] to 1.2% [95% CI, 0.3%-2.2%]), and poor diet quality (from 76.1% [95% CI, 74.0%-78.2%] to 71.7% [95% CI, 68.5%-74.9%]), and a decrease in the prevalence of hypertension (from 8.1% [95% CI, 6.9%-9.4%] to 5.5% [95% CI, 3.7%-7.3%]), hyperlipidemia (from 34.2% [95% CI, 30.9%-37.5%] to 22.8% [95% CI, 18.7%-26.8%]), cigarette use (from 18.0% [95% CI, 15.7%-20.3%] to 3.5% [95% CI, 2.0%-5.0%]), and inactive physical activity (from 83.0% [95% CI, 80.7%-85.3%] to 9.5% [95% CI, 4.2%-14.8%]). Sex and race/ethnicity affected the evolution of CVRF prevalence differently. Whilst treatment rates for hypertension and diabetes did not improve significantly (from 9.6% [95% CI, 3.5%-15.8%] to 6.0% [95% CI, 1.4%-10.6%]; from 51.0% [95% CI, 23.3%-78.7%] to 26.5% [95% CI, 0.0%-54.7%]; respectively), BP control was relatively stable (from 75.7% [95% CI, 56.8%-94.7%] to 73.5% [95% CI, 40.3%-100.0%]), while glycemic control improved to a certain extent, although it remained suboptimal (from 11.8% [95% CI, 0.0%-31.5%] to 62.7% [95% CI, 62.7%-62.7%]). CONCLUSIONS: From 2001 to March 2020, although prediabetes and overweight/obesity increased, hypertension, hyperlipidemia, cigarette use, and inactive physical activity decreased among US adolescents aged 12 to 19 years, whereas elevated BP, diabetes, and poor diet quality remained unchanged. There were disparities in CVRF prevalence and trends across sociodemographic subpopulations. While treatment and control rates for hypertension and diabetes plateaued, BP control were stable, and improved glycemic control was observed.