Self-Sensing Electromechanical System Integrated with the Embedded Displacement Sensor.

Conventionally, the electromechanical system requires the installation of auxiliary displacement sensors and only the amount on the drive part and motion end, which increases volume, cost, and measurement error in the system. This paper presents an integrated measurement method with a sensing head, which takes the equal division characteristics of mechanical structures as part of the sensor, thus, the so-called self-sensing system. Moreover, the displacement is measured by counting the time pulses. The sensing head is integrated with the entire electromechanical system, including the driving, transmitting, and moving parts. Thus, the integration of the sensing part is greatly improved. Taking the rotary table as a special example, and the sensing head embedded into each part of the system, displacement information is obtained by the common processing system and fused by the adaptive weighted average method. The results of the experiment show that the fusion precision of each component is higher than only the motor position information as the feedback. The proposed method is a practical self-sensing technology with significant volume reduction and intelligent control benefits in the industry, especially suitable for extremely small and narrow spaces.

Soy Protein Isolate Gel Subjected to Freezing Treatment: Influence of Methylcellulose and Sodium Hexametaphosphate on Gel Stability, Texture and Structure.

Freezing affects texture and induces the loss of gel quality. This study investigated the effects of methylcellulose (MC) (0.2%, 0.4%, 0.6%) and sodium hexametaphosphate (SHMP) (0.15%, 0.3%) on the gel textural and structural properties of SPI gels before and after freezing, and explores the synergistic enhancement of gel texture and the underlying mechanisms resulting from the simultaneous addition of SHMP and MC to SPI gels. It was revealed that MC improved the strength of SPI gels through its thickening properties, but it could not inhibit the reduction of SPI gels after freezing. The 0.4% MC-SPI gel exhibited the best gel strength (193.2 ± 2.4 g). SHMP inhibited gel reduction during freezing through hydrogen bonding and ionic interactions; it enhanced the freezing stability of SPI gels. The addition of 0.15% SHMP made the water-holding capacity in SPI gels reach the highest score after freezing (58.2 ± 0.32%). The synergistic effect of MC and SHMP could improve the strength and the freezing stability of SPI gels. MC facilitated the release of ionizable groups within SPI, causing negatively charged SHMP groups to aggregate on the SPI and inhibit the freezing aggregation of proteins. These results provide a strong basis for the improvement of cryogenic soy protein gel performance by SHMP and MC.

Magnesium status modulating the effect of serum vitamin D levels on retinopathy: National Health and Nutrition Examination Survey 2005 to 2008.

Aim: Magnesium levels may influence the effect of vitamin D levels on the body. This study aimed to assess the combined effect of magnesium status as reflected by magnesium depletion score (MDS) and vitamin D status on the risk of retinopathy. Methods: This cross-sectional study included participants aged 40 years and older with complete information on vitamin D, MDS, and retinopathy assessment from the 2005-2008 National Health and Nutrition Examination Survey (NHANES). Logistic regression analysis was utilized to analyze the relationship of MDS and vitamin D with retinopathy and expressed as odds ratio (OR) and 95% confidence interval (CI). Results: Of these 4,953 participants included, 602 (9.53%) participants had retinopathy. Serum vitamin D levels ≤30 nmol/L (vs. >30 nmol/L) (OR = 1.38, 95%CI: 1.05-1.81) and MDS >2 points (vs. ≤2 points) (OR = 1.47, 95%CI: 1.01-2.16) were associated with higher odds of retinopathy. There was an interaction between MDS and vitamin D on the increased odds of retinopathy (OR = 2.29, 95%CI: 1.12-4.68, P interaction = 0.025). In different MDS groups, serum vitamin D levels ≤30 nmol/L increased the odds of retinopathy only in the MDS >2 group (OR = 2.90, 95%CI: 1.16-7.24), but not in the MDS ≤2 group (p = 0.293). Subgroups analyses demonstrated that the interaction between MDS and serum vitamin D on retinopathy was observed in males (OR = 6.88, 95%CI: 1.41-33.66, P interaction = 0.019), people with diabetes (OR = 3.43, 95%CI: 1.78-6.63, P interaction < 0.001), and people with body mass index (BMI) ≥25 kg/m2 (OR = 2.46, 95%CI: 1.11-5.44, P interaction = 0.028). Conclusion: Magnesium plays a moderating role in the relationship between serum vitamin D and retinopathy. The protective effect of vitamin D against retinopathy was primarily present among those with inadequate magnesium levels.

Electrostatic doping tunable magnetic transition and half-metallicity in the monolayer CrCTe3.

The electrical manipulation of the magnetic transition and spin-polarized states has attracted extensive attention in the field of spintronics. In this work, we perform a detailed study on the electronic and magnetic properties of the carrier-doped monolayer CrCTe3by using first-principles calculation. It is found that, the magnetic transition from Néel-antiferomagnetic (nAFM) to ferromagnetic (FM) is observed in the case of the electron doping, while for hole doping a magnetic transition sequence of nAFM→zigzag-AFM→FM is observed in the monolayer CrCTe3. Interestingly, the carrier doping induced FM ground state always exhibits half-metallicity with full spin polarization. Moreover, the spin polarity of the half-metallic electronic states is opposite for electron and hole doping, meaning that the spin polarization direction can be tuned by manipulating a gate voltage. The Monte Carlo calculations show that the magnetic transition temperature of the doped FM CrCTe3is rapidly increased with the increasing doping concentration and is extremely expected to achieve room temperature at a suitable doping concentration. These findings demonstrate that the monolayer AFM system possesses a potential application in spintronic devices with electrically tunable spin polarization.

Polycyclic aromatic hydrocarbons exposure and arterial stiffness-related plasma miRNAs: A panel study.

The underlying mechanisms between polycyclic aromatic hydrocarbons (PAHs) exposure and arterial stiffness are poorly understood. We carried out a panel study involving three repeated surveys to examine the associations of individual and mixture of PAHs exposure with arterial stiffness-related miRNAs among 123 community adults. In linear mixed-effect (LME) models, we found that urinary 9-hydroxyfluorene (9-OHFlu), 2-hydroxyphenanthrene (2-OHPh), 9-hydroxyphenanthrene (9-OHPh) at lag 0 day were positively linked to miR-146a and/or miR-222. The Bayesian kernel machine regression (BKMR) analyses revealed positive overall associations of PAHs mixture at lag 0 day with miR-146a and miR-222, and urinary 9-OHFlu contributed the most. In addition, an inter-quartile range (IQR) increase in urinary 9-OHFlu at lag 0 day was associated with elevated miR-146a and miR-222 by 0.16 (95% CI: 0.02, 0.30) to 0.34 (95% CI: 0.13, 0.54). Accordingly, exposure to PAHs, especially 9-OHFlu at lag 0 day, was related to elevated arterial stiffness-related plasma miRNAs.

Corrigendum: Sesquiterpene lactones attenuate paclitaxel resistance via inhibiting MALAT1/STAT3/ FUT4 axis and P-Glycoprotein transporters in lung cancer cells.

[This corrects the article DOI: 10.3389/fphar.2022.795613.].

Association Between ACE2 and Lung Diseases.

Angiotensin-converting enzyme 2 (ACE2) is an important regulator of the Renin-Angiotensin System (RAS). Additionally, it has been identified as a functional receptor for the Coronavirus. Research indicates that ACE2 plays a role in the regulation of cardiovascular systems by modulating blood pressure and electrolyte balance. Its role in pulmonary diseases has also garnered significant attention due to the widespread prevalence of Coronavirus. There is solid evidence linking ACE2 to other pulmonary diseases, including chronic obstructive pulmonary disease, acute respiratory distress syndrome, allergic asthma, among others. However, the exact pathological and physiological mechanisms of ACE2 in these diseases remain elusive. Our research aims to review and explore the latest advancements in ACE2-related studies in pulmonary diseases. These findings have the potential to open new avenues for utilizing ACE2 as a potential biomarker for early diagnosis and monitoring of pulmonary diseases.

Effective cryopreservation of human brain tissue and neural organoids.

Human brain tissue models and organoids are vital for studying and modeling human neurological disease. However, the high cost of long-term cultured organoids inhibits their wide-ranging application. It is therefore urgent to develop methods for the cryopreservation of brain tissue and organoids. Here, we establish a method using methylcellulose, ethylene glycol, DMSO, and Y27632 (termed MEDY) for the cryopreservation of cortical organoids without disrupting the neural cytoarchitecture or functional activity. MEDY can be applied to multiple brain-region-specific organoids, including the dorsal/ventral forebrain, spinal cord, optic vesicle brain, and epilepsy patient-derived brain organoids. Additionally, MEDY enables the cryopreservation of human brain tissue samples, and pathological features are retained after thawing. Transcriptomic analysis shows that MEDY can protect synaptic function and inhibit the endoplasmic reticulum-mediated apoptosis pathway. MEDY will enable the large-scale and reliable storage of diverse neural organoids and living brain tissue and will facilitate wide-ranging research, medical applications, and drug screening.

WTAP-mediated m6A modification of lncRNA Snhg1 improves myocardial ischemia-reperfusion injury via miR-361-5p/OPA1-dependent mitochondrial fusion.

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is caused by reperfusion after ischemic heart disease. LncRNA Snhg1 regulates the progression of various diseases. N6-methyladenosine (m6A) is the frequent RNA modification and plays a critical role in MIRI. However, it is unclear whether lncRNA Snhg1 regulates MIRI progression and whether the lncRNA Snhg1 was modified by m6A methylation. METHODS: Mouse cardiomyocytes HL-1 cells were utilized to construct the hypoxia/reoxygenation (H/R) injury model. HL-1 cell viability was evaluated utilizing CCK-8 method. Cell apoptosis, mitochondrial reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were quantitated utilizing flow cytometry. RNA immunoprecipitation and dual-luciferase reporter assays were applied to measure the m6A methylation and the interactions between lncRNA Snhg1 and targeted miRNA or target miRNAs and its target gene. The I/R mouse model was constructed with adenovirus expressing lncRNA Snhg1. HE and TUNEL staining were used to evaluate myocardial tissue damage and apoptosis. RESULTS: LncRNA Snhg1 was down-regulated after H/R injury, and overexpressed lncRNA Snhg1 suppressed H/R-stimulated cell apoptosis, mitochondrial ROS level and polarization. Besides, lncRNA Snhg1 could target miR-361-5p, and miR-361-5p targeted OPA1. Overexpressed lncRNA Snhg1 suppressed H/R-stimulated cell apoptosis, mitochondrial ROS level and polarization though the miR-361-5p/OPA1 axis. Furthermore, WTAP induced lncRNA Snhg1 m6A modification in H/R-stimulated HL-1 cells. Moreover, enforced lncRNA Snhg1 repressed I/R-stimulated myocardial tissue damage and apoptosis and regulated the miR-361-5p and OPA1 levels. CONCLUSION: WTAP-mediated m6A modification of lncRNA Snhg1 regulated MIRI progression through modulating myocardial apoptosis, mitochondrial ROS production, and mitochondrial polarization via miR-361-5p/OPA1 axis, providing the evidence for lncRNA as the prospective target for alleviating MIRI progression.

Identifying biomarkers of ginseng medicines with different natures on heart failure.

ETHNOPHARMACOLOGICAL RELEVANCE: The nature of Chinese medicine is a unique index to measure its efficacy. Generally, treating the hot syndrome with cold nature medicine and vice versa. Ginseng medicines, a renowned Chinese medicine known for its qi tonifying action, encompasses various herbal materials such as ginseng, red ginseng, and black ginseng (GS, RG, and BG, respectively), ginseng leaves (GL), and American ginseng (AG), which exhibited different natures, thought contained similar ginsenosides. This traditional effect of GS and RG "reinvigorate the pulse for relieving qi depletion". It is closely linked to anti-heart failure (HF), HF is a clinical manifestation of deficiency of "heart-qi". However, the elucidation of the mechanism underlying the anti-HF effects of ginseng medicines with different natures remains a significant challenge. AIM OF THE STUDY: To elucidate pharmacological mechanisms underlying the effect of ginseng medicines on HF, and to identify biomarkers associated with their various natures. Furthermore, it provides the basis for the different applications of ginseng medicines with various natures. MATERIALS AND METHODS: This study established a rat model of HF induced by isoproterenol (ISO) combined with a specific diet. Four representative hot/cold herbs were selected as compared references for the medicine natures. The divergent effects of these herbs on the HF model were investigated by analyzing RNA-seq data to identify genes expressed differentially. Additionally, pathways associated with medicine natures were obtained using KEGG. Furthermore, UPLC-QqQ-MS/MS, as well as ELISA, were used to measure indexes associated with the nervous system, energy metabolisms, and endocrinology systems, such as BNP, CK, IL-1, T3, T4, cAMP, cGMP, AD, adrenal hormones (DOC, CORT, and COR), progestogens (pregnenolone, P, 17-OH-PR, and 17-OH-P), androgens (DHEA, A4, and T), and estrogens hormones (E2). RESULTS: All ginseng medicines demonstrated varying levels of efficacy in alleviating HF and GS exhibited a significant protective effect on HF. The ginseng medicines with qi tonifying primarily achieve their effect by enhancing the levels of adrenal hormones (DOC, CORT, and COR), T4, elevation of cAMP/cGMP, and activation of AchE. Warm nature qi tonifying ginseng medicines increased the levels of 17-OH-PR and P while decreasing 17-OH-P and the ratio of E2/T. On the other hand, cold nature qi tonifying ginseng medicines decreased the levels of A4 and T while increasing the ratio of E2/T. CONCLUSION: Overall, the effects of warm nature ginseng medicines are stronger on HF compared to cold nature ginseng medicines. Our research firstly reported that the E2/T ratio, progestogens (17-OH-PR, 17-OH-P, and P), and androgens (A4 and T) have been identified as significant biomarkers for discerning the mechanism differences of ginseng medicines with differences natures in treatment of HF.

Validation and comparison of 5th edition World Health Organization classification (WHO 2022) and International Consensus Classification proposals for MDS-SFB31.

The criteria of myelodysplastic syndromes (MDS) with mutated SFB31 (MDS-SFB31) proposed by the 5th edition of the WHO classification (WHO 2022) and the International Consensus Classification (ICC) need validation. We analysed 125 consecutive MDS cases with SFB31 mutation or ring sideroblasts (RS) ≥15% without excess blasts. We found that SFB31-negative MDS with RS had significantly different clinical features and worse prognosis. According to WHO 2022, the detection of ≥15% RS may substitute for SF3B1 mutation and our analyses support this proposal for similar prognosis of two groups after excluding high-risk genetic features referred by WHO 2022. Patients with variant allele frequency (VAF) <10% SFB31 tend to have briefer survival, supporting the VAF 10% threshold of ICC. Patients with multilineage dysplasia (MLD) had significantly shorter OS than those with single lineage dysplasia. MLD is still a powerful morphological marker of worse outcome in WHO 2022 and ICC-defined MDS-SF3B1.

Constructed Rice Tracers Identify the Major Virulent Transcription Activator-Like Effectors of the Bacterial Leaf Blight Pathogen.

Xanthomonas oryzae pv. oryzae (Xoo) injects major transcription activator-like effectors (TALEs) into plant cells to activate susceptibility (S) genes for promoting bacterial leaf blight in rice. Numerous resistance (R) genes have been used to construct differential cultivars of rice to identify races of Xoo, but the S genes were rarely considered. Different edited lines of rice cv. Kitaake were constructed using CRISPR/Cas9 gene-editing, including single, double and triple edits in the effector-binding elements (EBEs) located in the promoters of rice S genes OsSWEET11a, OsSWEET13 and OsSWEET14. The near-isogenic lines (NILs) were used as tracers to detect major TALEs (PthXo1, PthXo2, PthXo3 and their variants) in 50 Xoo strains. The pathotypes produced on the tracers determined six major TALE types in the 50 Xoo strains. The presence of the major TALEs in Xoo strains was consistent with the expression of S genes in the tracers, and it was also by known genome sequences. The EBE editing had little effect on agronomic traits, which was conducive to balancing yield and resistance. The rice-tracers generated here provide a valuable tool to track major TALEs of Xoo in Asia which then shows what rice cultivars are needed to combat Xoo in the field.

Risk Factors of Tuberculosis Destroyed Lung in Patients with Pulmonary Tuberculosis and Structural Lung Diseases: A Retrospective Observational Study.

Background: Tuberculosis destroyed lung constitutes a significant worldwide public health challenge, little is known about its associated risk factors and prognosis. Our study aimed to identify the risk factors of tuberculosis destroyed lung among pulmonary tuberculosis and structural lung diseases. Methods: Between January 2019 and December 2021, a case-control study was conducted at the Third People's Hospital of Shenzhen in China. We collected the clinical data among patients with pulmonary tuberculosis and structural lung diseases. Cases were defined as patients with tuberculosis destroyed lung. Controls were not diagnosed with the tuberculosis destroyed lung. A binary logistic regression was performed. Results: In our study, a total of 341 patients met the inclusion criteria, including 182 cases and 159 controls. We found that age ranges of 46-60 years (aOR: 4.879; 95% CI: 2.338-10.180), >60 years (aOR: 3.384; 95% CI: 1.481-7.735); history of TB treatment (aOR: 2.729; 95% CI: 1.606-4.638); malnutrition (aOR: 5.126; 95% CI: 1.359-19.335); respiratory failure (aOR: 5.080; 95% CI: 1.491-17.306); and bronchiarctia (aOR: 3.499; 95% CI: 1.330-9.209) were the independent risk factors for tuberculosis destroyed lung. Conversely, having a normal (aOR: 0.207; 95% CI: 0.116-0.371) or overweight BMI (aOR: 0.259; 95% CI: 0.090-0.747) emerged as a protective factor against tuberculosis destroyed lung. Conclusion: This study indicated that tuberculosis destroyed lung is a common condition among patients with pulmonary tuberculosis and structural lung diseases. The independent risk factors for tuberculosis destroyed lung were identified as being within the age groups of 46-60 and over 60 years, having a previous history of TB treatment, malnutrition, respiratory failure, and bronchiarctia. It is essential to closely monitor patients possessing these risk factors to prevent the progression towards tuberculosis destroyed lung.

A new nomogram to predict in-hospital mortality in patients with acute decompensated chronic heart failure and diabetes after 48 Hours of Intensive Care Unit.

BACKGROUND: The study set out to develop an accurate and clinically valuable prognostic nomogram to assess the risk of in-hospital death in patients with acute decompensated chronic heart failure (ADCHF) and diabetes. METHODS: We extracted clinical data of patients diagnosed with ADCHF and diabetes from the Medical Information Mart for Intensive Care III database. Risk variables were selected utilizing least absolute shrinkage and selection operator regression analysis, and were included in multivariate logistic regression and presented in nomogram. bootstrap was used for internal validation. The discriminative power and predictive accuracy of the nomogram were estimated using the area under the receiver operating characteristic curve (AUC), calibration curve and decision curve analysis (DCA). RESULTS: Among 867 patients with ADCHF and diabetes, In-hospital death occurred in 81 (9.3%) patients. Age, heart rate, systolic blood pressure, red blood cell distribution width, shock, ß-blockers, angiotensin converting enzyme inhibitors or angiotensin receptor blockers, assisted ventilation, and blood urea nitrogen were brought into the nomogram model. The calibration curves suggested that the nomogram was well calibrated. The AUC of the nomogram was 0.873 (95% CI: 0.834-0.911), which was higher that of the Simplified Acute Physiology Score II [0.761 (95% CI: 0.711-0.810)] and sequential organ failure assessment score [0.699 (95% CI: 0.642-0.756)], and Guidelines-Heart Failure score [0.782 (95% CI: 0.731-0.835)], indicating that the nomogram had better ability to predict in-hospital mortality. In addition, the internally validated C-index was 0.857 (95% CI: 0.825-0.891), which again verified the validity of this model. CONCLUSIONS: This study constructed a simple and accurate nomogram for predicting in-hospital mortality in patients with ADCHF and diabetes, especially in those who admitted to the intensive care unit for more than 48 hours, which contributed clinicians to assess the risk and individualize the treatment of patients, thereby reducing in-hospital mortality.

Design, synthesis, and activity evaluation of 2-iminobenzimidazoles as c-Myc inhibitors for treating multiple myeloma.

Multiple myeloma (MM) is a plasma cell malignancy that remains incurable and poses a significant threat to global public health. The multifunctional transcription factor c-Myc plays a crucial role in various cellular processes and is closely associated with MM progression. As part of the basic-helix-loop-helix-leucine zipper (bHLHZip) family, c-Myc forms heterodimers with its obligate partner Max, binds to the Enhancer-box (E-box) of DNA, and ultimately co-regulates gene expression. Therefore, impeding the capacity for heterodimerization to bind to DNA represents a favored strategy in thwarting c-Myc transcription. In this study, we first synthesized a series of novel 2-iminobenzimidazole derivatives and further estimated their potential anti-MM activity. Notably, among all the derivatives, 5b and 5d demonstrated remarkable inhibitory activity against RPMI-8226 and U266 cells, with IC50 values of 0.85 µM and 0.97 µM for compound 5b, and 0.96 µM and 0.89 µM for compound 5d. Western blot and dual-luciferase reporter assays demonstrated that compounds 5b and 5d effectively suppressed both c-Myc protein expression and transcriptional activity of the c-Myc promoter in RPMI-8226 and U266 cells. Furthermore, these compounds induced apoptosis and G1 cell cycle arrest in the aforementioned MM cells. Molecular docking studies revealed that 5b and 5d exhibited strong binding affinity to the interface between c-Myc/Max and E-box of DNA. Taken together, our findings suggest that further investigations are warranted for potential therapeutic applications of 5b and 5d for c-Myc-related diseases.

Interactive effects of dinotefuran and Nosema ceranae on the survival status and gut microbial community of honey bees.

Growing evidences have shown that the decline in honey bee populations is mainly caused by the combination of multiple stressors. However, the impacts of parasitic Nosema ceranae to host fitness during long-term pesticide exposure-induced stress is largely unknown. In this study, the effects of chronic exposure to a sublethal dose of dinotefuran, in the presence or absence of N. ceranae, was examined in terms of survival, food consumption, detoxification enzyme activities and gut microbial community. The interaction between dinotefuran and Nosema ceranae on the survival of honey bee was synergistic. Co-exposure to dinotefuran and N. ceranae led to less food consumption and greater changes of enzyme activities involved in defenses against oxidative stress. Particularly, N. ceranae and dinotefuran-N. ceranae co-exposure significantly impacted the gut microbiota structure and richness in adult honey bees, while dinotefuran alone did not show significant alternation of core gut microbiota compared to the control group. We herein demonstrated that chronical exposure to dinotefuran decreases honey bee's survival but is not steadily associated with the gut microbiota dysbiosis; by contrast, N. ceranae parasitism plays a dominant role in the combination in influencing the gut microbial community of the host honey bee. Our findings provide a comprehensive understanding of combinatorial effects between biotic and abiotic stressors on one of the most important pollinators, honey bees.

Mechanism of l-cysteine-induced fibrous structural changes of soybean protein at different high-moisture extrusion zones.

In this study, the fibrous structure formation mechanism of soybean protein during high moisture extrusion processing was investigated using a dead-stop operation, and based on the interaction between soybean protein concentrate (SPC) and L-cysteine (CYS). The thermal properties, SDS-PAGE and particle size distribution of the samples from different extrusion zones were investigated. It was revealed that the addition of a moderate amount of CYS (0.1 %) promoted the fibrous structure formation in the SPC extrudates and optimised the textural properties of the SPC extrudates. In the extruder barrel, addition of CYS (0.1 %) promoted protein depolymerisation and unfolding in the mixing and cooking zones, and facilitated protein aggregation in the die and cooling zones. Protein solubility and raman spectroscopy revealed that disulfide bonds were principally responsible for fibrous structure formation; favoured when the intermolecular disulfide bonds (t-g-t mode) was increased. Finally, the transformation of protein conformation was revealed by secondary structure and surface hydrophobicity, which confirmed that the effect of CYS on protein conformation mainly occurred in the cooling zone. This study provides a theoretical basis for the application of CYS to regulate the fibrous structure of meat analogues.

The short-term outcome of intracranial stenosis with distal thrombosis treated with balloon-assisted tracking.

Background and purposes: Treating intracranial stenosis with distal thrombosis (IS&DT) using traditional mechanical thrombectomy (MT) techniques has proven challenging. This study aimed to summarize the experience of utilizing the balloon-assisted tracking (BAT) technique for IS&DT. Methods: Demographic and morphologic characteristics of patients with IS&DT were collected for this study. The BAT technique, involving a half-deflated balloon outside the intermediate catheter tip, was used in all patients to navigate through the proximal stenosis. Various parameters were recorded, including the sequence of vascular reperfusion, the puncture-to-reperfusion time (PRT), the residual stenosis rate, and the occurrence of re-occlusion. The thrombolysis in cerebral infarction (TICI) scale was used to assess the reperfusion of intracranial vessels, with a TICI score of ≥2b considered as successful perfusion. The clinical status of patients was evaluated at three time points: pre-procedure, post-procedure, and at discharge using the modified Rankin score (mRS). Results: In this study, a total of 10 patients were diagnosed with IS&DT, consisting of 9 male patients (90.0%) and 1 female patient (10.0%). The patients' mean age was 63.10 years (ranging from 29 to 79 years). The mean National Institute of Health Stroke Scale (NIHSS) score before treatment was 24.3 (ranging from 12 to 40), indicating the severity of their condition. Following the procedure, all patients achieved successful reperfusion with a thrombolysis in cerebral infarction (TICI) score of ≥2b. The average puncture-to-reperfusion time (PRT) was 51.8 min (ranging from 25 to 100 min), indicating the time taken for the procedure. During the perioperative period, three patients (30.0%) experienced complications. One patient had hemorrhage, while two patients had contrast extravasation. Among these cases, only the patient with hemorrhage (10%) suffered from a permanent neurological function deficit. At discharge, the patient's condition showed improvement. The mean NIHSS score decreased to 13.2 (ranging from 1 to 34), indicating a positive response to treatment. The mean mRS score at discharge was 3.2 (ranging from 1 to 5), showing some level of functional improvement. Conclusion: In conclusion, the use of the balloon-assisted tracking (BAT) technique for treating intracranial stenosis with distal thrombosis (IS&DT) showed promising results. However, a moderate rate of perioperative complications was observed, warranting further investigation and refinement of the procedure.

CsMYB73 negatively regulates theanine accumulation mediated by CsGGT2 and CsGGT4 in tea shoots (Camellia sinensis).

Theanine metabolism is a necessary biological process during the planting and production of tea that determines tea quality. There is currently little knowledge about the transcriptional regulation of theanine metabolism in tea plants. In this study, we demonstrated that γ-glutamyl-transpeptidase CsGGT4, as a homologous protein of the theanine hydrolase CsGGT2, exhibited a higher theanine synthesis catalytic efficiency. Homology modeling and molecular docking showed that differential protein structures between CsGGT2 and CsGGT4 implied their different biological functions in tea plants. Theanine content correlated significantly with the expression of CsGGT2, CsGGT4 and the transcription factor CsMYB73 in tea shoots from different seasons. Additionally, CsMYB73 was confirmed to act as a nucleus-localized transcription factor (TF), directly interacts with the CsGGT2 and CsGGT4 promoters, serving as an activator of CsGGT2 and a suppressor of CsGGT4. Consequently, this leads to a negative association with theanine accumulation in tea shoots. Furthermore, the continuous increase in CsMYB73 produced a significantly increase in CsGGT2 expression and inhibited CsGGT4 expression. The present study reveals that the degradation of theanine has been observed to increase, concomitantly with the inhibition of theanine synthesis, resulting in a significant decline in the accumulation of theanine in tea shoots during the process of seasonal greening in 'Huangkui' leaves. This study contributes to the broader comprehension of the intricate transcriptional regulatory hierarchy that governs the metabolism of theanine in tea shoots, offering novel approaches for managing tea plantations and enhancing tea quality.

Radiation-Activated Resiquimod Prodrug Nanomaterials for Enhancing Immune Checkpoint Inhibitor Therapy.

Immune checkpoint inhibitor (ICI) therapy is effectively employed in treating various malignancies. However, the response rate is constrained to 5-30%, which is attributed to differences in immune responses across different tumors. Overcoming all obstacles of multistep immune activation with monotherapy is difficult. Here, maleimide-modified resiquimod (R848) prodrug nanoparticles (MAL-NPs) are reported and combined with radiotherapy (RT) and anti-PD1 to enhance ICI therapy. MAL-NPs can promote antigen endocytosis by dendritic cells and are radio-reduced to produce R848. When combined with RT, MAL-NPs can augment the concentration of nanoparticles at tumor sites and be selectively radio-reduced within the tumor, thereby triggering a potent antitumor immune response. The systemic immune response and long-term memory efficacy induced by MAL-NPs + RT + anti-PD1 significantly inhibit the abscopal tumor growth and prevent tumor recurrence. This strategy can achieve systemic therapy through selective training of the tumor immune microenvironment, offering a new approach to overcome the obstacles of ICI therapy.