Correlations of dynamic changes in lipid and protein of salted large yellow croaker during storage.

Protein and lipid are two major components that undergo significant changes during processing of aquatic products. This study focused on the protein oxidation, protein conformational states, lipid oxidation and lipid molecule profiling of salted large yellow croaker during storage, and their correlations were investigated. The degree of oxidation of protein and lipid was time-dependent, leading to an increase in carbonyl content and surface hydrophobicity, a decrease in sulfhydryl groups, and an increase in conjugated diene, peroxide value and thiobarbituric acid reactive substances value. Oxidation caused protein structure denaturation and aggregation during storage. Lipid composition and content changed dynamically, with polyunsaturated phosphatidylcholine (PC) was preferentially oxidized compared to polyunsaturated triacylglycerol. Correlation analysis showed that the degradation of polyunsaturated key differential lipids (PC 18:2_20:5, PC 16:0_22:6, PC 16:0_20:5, etc.) was closely related to the oxidation of protein and lipid. The changes in protein conformation and the peroxidation of polyunsaturated lipids mutually promote each other's oxidation process.

The potential therapeutic roles of dental pulp stem cells in spinal cord injury.

Spinal cord injury (SCI) can lead to serious functional disorders, which have serious impacts on patients and society. The current traditional treatments of SCI are not effective the injured spinal cord is difficult to repair and regenerate. In recent years, stem cell transplantation for the treatment of SCI has been a hot research topic. Dental pulp stem cells have strong abilities of self-renewal and multi-directional differentiation, and have been applied for tissue engineering and regenerative medicine. And dental pulp stem cells have certain advantages in neuro-regenetation, bringing new hope to biotherapy for SCI. This article reviews the characteristics of dental pulp stem cells and their research progress in the treatment of SCI.

Lifestyle factors and subjective well­being among older adults in China: A national community-based cohort study.

There has been limited research on the relationship between health habits and subjective well-being (SWB) among Chinese oldest older adults. This study aims to explore lifestyle factors associated with SWB in this population. We analyzed data from three waves (2008-2014) of the CLHLS, including 28,683 older adults. Lifestyle factors analyzed included fruit and vegetable intake, smoking, alcohol consumption, physical exercise, and social participation. Results suggested that high frequency of fruit and vegetable intake, current and past physical exercise, and high levels of social participation were associated with increased SWB. SWB was lower in older adults who never smoked compared to persistent smokers and in those who never drank alcohol or ceased drinking compared to persistent drinkers. We encourage older adults to enhance SWB through increased fruit and vegetable intake, physical exercise, and social participation. However, quitting smoking and drinking may not necessarily improve SWB, particularly in the context of China.

Validating the Baveno Elastography Criteria of Advanced Liver Fibrosis in Two-dimensional Shear Wave Elastography: A Prospective Pathology-based Study.

INTRODUCTION: The Baveno criteria for assessing advanced liver fibrosis were mainly determined by transient elastography (TE), and its pathology-based validation studies in two-dimensional shear-wave elastography (2D-SWE) remain limited. We aimed to validate the Baveno criteria through use of 2D-SWE. METHOD: Consecutive patients who underwent liver biopsies for various benign liver diseases were prospectively recruited. Liver stiffness measurement (LSM) was simultaneously evaluated by TE and 2D-SWE. The optimal cut-off value to predict advanced liver fibrosis was determined by the Youden Index, and the diagnostic performance was estimated using area under the receiver operating characteristic (AUROC) analysis. RESULTS: A total of 101 patients were enrolled having a median age of 55.0 (IQR: 46.0-63.5) years, with 53 (52.48%) of them being male. Using <9 and >14 kPa as the optimal dual cut-offs, the AUROC values in TE and 2D-SWE were 0.92 (95% CI: 0.83-0.97) and 0.93 (95% CI: 0.84-0.98), respectively (P= 0.61). The sensitivity and specificity of LSM by TE/2D-SWE achieved rates of 94.44%/94.44% and 86.00%/88.00%, respectively. However, using the Baveno criteria, the AUROC values in TE and 2D-SWE could remain achieving 0.91 (95% CI: 0.82-0.97) and 0.93 (95% CI: 0.84-0.98), respectively (P= 0.36). The sensitivity and specificity in TE/2D-SWE were 88.24%/88.24% and 86.79%/90.57%, respectively. CONCLUSION: This study establishes the compatibility of the Baveno dual cut-off criteria with 2D-SWE, positioning it as an easily used criteria in clinical practice and research.

Novel method for identifying the heaviest QED atom.

QED atoms are composed of unstructured and point-like lepton pairs bound together by the electromagnetic force. The smallest and heaviest QED atom is formed by a τ+τ- pair. Currently, the only known atoms of this type are the e+e- and µ+e- atoms, which were discovered 64 years ago and remain the sole examples found thus far. We demonstrate that the Jτ (τ+τ- atom with JPC=1--) atom signal can be observed with a significance larger than 5σ including both statistical and systematic uncertainties, via. the process e+e-→X+Y-Ɇ (X,Y=e,µ,π,K, or ρ, and Ɇ is the missing energy due to unobserved neutrinos) with 1.5ab-1 data taken around the τ pair production threshold. The τ lepton mass can be measured with a precision of 1 keV with the same data sample. This is within one year's running time of the proposed super tau-charm facility in China or super charm-tau factory in Russia.

[Research progress on processing history evolution, chemical constituents, and pharmacological action of Scorpio].

Scorpio is a valuable Chinese animal medicine commonly used in clinical practice in China. It is the main drug in the treatment of liver wind internal movement caused by various reasons throughout the history of traditional Chinese medicine(TCM), with the effects of relieving wind and spasm, dredging collaterals, relieving pain, and eliminating toxin and mass. Scorpio is poisonous and often used as medicine after processing. There are records of its processing as early as the Song Dynasty. Afterward, there were more than 15 processing methods, including frying with vinegar, neat processing, and stir-frying. After processing, the fishy smell could be removed to correct the taste, and the toxicity could be reduced, which was beneficial to clinical application. At present, the main reported components in Scorpio are protein polypeptides, alkaloids, and lipids, with many pharmacological effects, such as anti-cancer, anti-coagulation, anti-thrombosis, anti-atherosclerosis, and anti-bacteria. In this study, the historical evolution of processing, chemical constituents, and pharmacological action of Scorpio were discussed in order to provide references for the related research on Scorpio.

Impact of thermal ultrasound on enzyme inactivation and flavor improvement of sea cucumber hydrolysates.

In this study, the effects of the thermal ultrasonic enzyme inactivation process on flavor enhancement in sea cucumber hydrolysates (SCHs) and its impact on the inactivation of neutral proteases (NPs) were investigated. The body wall of the sea cucumber was enzymatically hydrolyzed with NPs. On the one hand, the structure of NPs subjected to different enzyme inactivation methods was analyzed using ζ-potential, particle size, and Fourier transform infrared (FT-IR) spectroscopy. On the other hand, the microstructure and flavor changes of SCHs were examined through scanning electron microscopy, E-nose, and gas chromatography-ion mobility spectrometry (GC-IMS). The results indicated that thermal ultrasound treatment at 60 °C could greatly affect the structure of NPs, thereby achieving enzyme inactivation. Furthermore, this treatment generated more pleasant flavor compounds, such as pentanal and (E)-2-nonenal. Hence, thermal ultrasound treatment could serve as an alternative process to traditional heat inactivation of enzymes for improving the flavor of SCHs.

Effects of cycloplegia on crystalline lens morphology and location in acute acquired concomitant esotropia.

PURPOSE: The study aims to compare morphology and location of crystalline lens between acute acquired concomitant esotropia (AACE) patients and control subjects, both before and after cycloplegia. METHODS: This is a prospective and observational clinical study. Morphological and locational parameters of the crystalline lens in 53 AACE patients and 32 control subjects were assessed before and after cycloplegia using CASIA2 system, which represents the latest swept-source anterior segment optical coherence tomography. Cycloplegic refraction was recorded by administering 1% atropine in patients younger than 12 years and 1% cyclopentolate in those > 12 years old. Morphological parameters included anterior radius of curvature (ARC), posterior radius of curvature (PRC), lens thickness (LTH), and equivalent diameter of lens (LED). Locational parameters comprised lens decentration (LD) and lens tilt (LT). Comparison of these parameters before and after cycloplegia were conducted between AACE and controls. Additionally, the study analyzed and compared the changes in these parameter post-cycloplegia. RESULTS: Our findings suggest no significant difference in morphological parameters including ARC, PRC, LTH and LED between AACE patients and controls before or after cycloplegia. However, 2D-modeling data in the 0° meridian revealed that variation post-cycloplegia of LD (lens shift) in right eyes was different in AACE patients, measuring - 0.03(0.08) [median(interquartile range)] which was significantly distinct from the control group, exhibiting a measurement of 0.01(0.06) (z = - 2.373, p = 0.018). In left eyes, a similar trend was observed with lens shift in the 0° meridian being 0.02(0.06) in AACE, significantly differing from control group's measurement of - 0.02(0.08) (z = - 2.809, p = 0.005). Further, correlation analysis revealed that larger temporal shift of lens was associated with greater changes in ARC (r = 0.294, p = 0.006) and LTH (r = - 0.230, p = 0.031). CONCLUSIONS: The morphological features of the crystalline lens were similar in AACE patients and controls; however, the change of lens location by cycloplegia was observed only in AACE patients, suggesting an association with excessive accommodation.

Fully digital workflow of occlusal reconstruction treatment in a patient with congenital dentition defects.

OBJECTIVE: Occlusal reconstruction is a critical intervention for patients with dental hard tissue defects, temporomandibular joint (TMJ) disorders, and jaw position abnormalities. Clinical efficiency and outcomes of these procedures have improved with advances in digital technologies. This case report aims to illustrate a comprehensive digital workflow for occlusal reconstruction in a patient with congenital dentition defects, emphasizing the application of digital technologies to enhance treatment outcomes. CLINICAL CONSIDERATIONS: A 28-year-old woman with previously installed porcelain-fused-to-metal bridge restorations presented with a fractured prosthesis and TMJ symptoms. A multidisciplinary approach was adopted involving the use of digital facebow, intraoral scanners, digital smile design, and CAD/CAM technologies. The process included the extraction of defective restorations, temporary restorations to refine jaw position, and final permanent restorations. The digital workflow facilitated precise diagnostics and treatment, culminating in the successful installation of permanent restorations. Regular follow-ups at one- and three-months post-treatment confirmed stable occlusal function and high patient satisfaction. CONCLUSIONS: This case report showcases the potential of multiple digital technologies to streamline complex dental treatments and achieve high-quality results. CLINICAL SIGNIFICANCE: The integration of digital technologies in occlusal reconstruction treatments offers significant benefits in terms of precision, patient comfort, and esthetic outcomes.

FAM120A deficiency improves resistance to cisplatin in gastric cancer by promoting ferroptosis.

The occurrence of chemoresistance is an inescapable obstacle affecting the clinical efficacy of cisplatin in gastric cancer (GC). Exploring the regulatory mechanism of cisplatin resistance will help to provide potential effective targets for improving the prognosis of gastric cancer patients. Here, we find that FAM120A is upregulated in GC tissues and higher in cisplatin-resistant GC tissues, and its high expression is positively correlated with the poor outcome of GC patients. Functional studies indicate that FAM120A confers chemoresistance to GC cells by inhibiting ferroptosis. Mechanically, METTL3-induced m6A modification and YTHDC1-induced stability of FAM120A mRNA enhance FAM120A expression. FAM120A inhibits ferroptosis by binding SLC7A11 mRNA and enhancing its stability. FAM120A deficiency enhances cisplatin sensitivity by promoting ferroptosis in vivo. These results reveal the function of FAM120A in chemotherapy tolerance and targeting FAM120A is an effective strategy to alleviate cisplatin resistance in GC.

Both gain- and loss-of-function variants of KCNA1 are associated with paroxysmal kinesignic dyskinesia.

KCNA1 is the coding gene for Kv1.1 voltage-gated potassium channel α subunit. Three variants of KCNA1 have been reported to manifest as paroxysmal kinesignic dyskinesia (PKD), but the correlation between them remains unclear due to the phenotypic complexity of KCNA1 variants as well as the rarity of PKD cases. Using the whole exome sequencing followed by Sanger sequencing, we screen potential pathogenic KCNA1 variants in patients clinically diagnosed with paroxysmal movement disorders and identify three previously unreported missense variants of KCNA1 in three unrelated Chinese families. The proband of one family (c.496G>A, p.A166T) manifests as episodic ataxia type 1, and the other two (c.877G>A, p.V293I; and c.1112C>A, p.T371A) manifest as PKD. The pathogenicity of these variants is confirmed by functional studies, suggesting that p.A166T and p.T371A cause a loss-of-function of the channel, while p.V293I leads to a gain-of-function with the property of voltage-dependent gating and activation kinetic affected. By reviewing the locations of PKD-manifested KCNA1 variants in Kv1.1 protein, we find that these variants tend to cluster around the pore domain, which is similar to epilepsy. Thus, our study strengthens the correlation between KCNA1 variants and PKD and provides more information on genotype-phenotype correlations of KCNA1 channelopathy.

Postpartum Necrotizing Myositis With Endometrial Prolapse.

BACKGROUND: Postpartum necrotizing myositis is a rare condition, typically presenting as a complication after uterine artery embolization or uterine compression suturing. Uterine ischemia can cause endometrial necrosis and even myometrial necrosis, which can lead to systemic infection. If a systemic infection is not promptly and actively treated, it may pose significant risk. CASE: A 35-year-old patient who had undergone bilateral uterine artery ligation, modified B-Lynch suture, and multiple compression sutures due to refractory postpartum hemorrhage frequently presented to clinic after postpartum discharge due to persistent fever and vaginal discharge. A bag-like prolapse from the vagina measuring 10×5 cm, accompanied by purulent discharge, was noted 78 days postsurgery. Subsequent pelvic magnetic resonance imaging revealed a uterine basal abscess and postpartum necrotizing myositis; an emergency laparoscopic supracervical hysterectomy was performed, with postoperative pathology confirming the diagnosis. After the patient's discharge, she was readmitted for inpatient treatment of a pelvic abscess. CONCLUSIONS: Although rare, postpartum necrotizing myositis should be considered in postpartum patients presenting with fever, abdominal pain, severe infection symptoms, and abnormal vaginal discharge. Culture and sensitivity testing are recommended to direct appropriate antibiotic therapy.

The protective effects of ruscogenin against lipopolysaccharide-induced myocardial injury in septic mice.

ABSTRACT: Sepsis-induced myocardial dysfunction (SIMD) commonly occurs in individuals with sepsis and is a severe complication with high morbidity and mortality rates. The current study aimed to investigate the effects and potential mechanisms of the natural steroidal sapogenin ruscogenin (RUS) against lipopolysaccharide (LPS)-induced myocardial injury in septic mice. We found that RUS effectively alleviated myocardial pathological damage, normalized cardiac function, and increased survival in septic mice. RNA sequencing (RNA-seq) demonstrated that RUS administration significantly inhibited the activation of the NOD-like receptor signaling pathway in the myocardial tissues of septic mice. Subsequent experiments further confirmed that RUS suppressed myocardial inflammation and pyroptosis during sepsis. Additionally, cultured HL-1 cardiomyocytes were challenged with LPS, and we observed that RUS could protect these cells against LPS-induced cytotoxicity by suppressing inflammation and pyroptosis. Notably, both the in vivo and in vitro findings indicated that RUS inhibited NLRP3 upregulation in cardiomyocytes stimulated with LPS. As expected, knockdown of NLRP3 blocked the LPS-induced activation of inflammation and pyroptosis in HL-1 cells. Furthermore, the cardioprotective effects of RUS on HL-1 cells under LPS stimulation were abolished by the novel NLRP3 agonist BMS-986299. Taken together, our results suggest that RUS can alleviate myocardial injury during sepsis, at least in part by suppressing NLRP3-mediated inflammation and pyroptosis, highlighting the potential of this molecule as a promising candidate for SIMD therapy.

Prevention of postoperative nausea and vomiting after orthognathic surgery: a scoping review.

INTRODUCTION: Postoperative nausea and vomiting (PONV) is one of the most common adverse events following orthognathic surgery. It's a distressing feeling for patients and continues to be the cause of postoperative complications such as bleeding, delayed healing, and wound infection. This scoping review aims to identify effective PONV prophylaxis strategies during orthognathic surgery that have emerged in the past 15 years. METHODS: We searched Pubmed, Cochrane Controlled Register of Trials, and Embase from 2008 to May 2023. Studies meeting the following criteria were eligible for inclusion: (1) recruited patients undergo any orthognathic surgery; (2) evaluated any pharmacologic or non-pharmacologic method to prevent PONV. Studies meeting the following criteria were excluded: (1) case series, review papers, or retrospective studies; (2) did not report our prespecified outcomes. RESULTS: Twenty-one studies were included in this review. Pharmacological methods for PONV prevention include ondansetron and dexamethasone (3 studies), peripheral nerve block technique (4 studies), dexmedetomidine (1 study), pregabalin (2 studies), nefopam (2 studies), remifentanil (1 study), propofol (2 studies), and penehyclidine (1 study). Non-pharmacologic methods include capsicum plaster (1 study), throat packs (2 studies) and gastric aspiration (2 studies). CONCLUSIONS: Based on current evidence, we conclude that prophylactic antiemetics like dexamethasone, ondansetron, and penehyclidine are the first defense against PONV. Multimodal analgesia with nerve block techniques and non-opioid analgesics should be considered due to their notable opioid-sparing and PONV preventive effect. For the non-pharmacological methods, throat packs are not recommended for routine use because of their poor effect and serious complications. More prospective RCTs are required to confirm whether gastric aspiration can prevent PONV effectively for patients undergoing orthognathic surgery.

Six-month binocular stereopsis recovery and its influencing factors in children with intermittent exotropia.

OBJECTIVE: To investigate the recovery of binocular stereopsis recovery and its influencing factors in children with intermittent exotropia after successful correction of eye position. METHODS: Prospective clinical study. A total of 178 patients, aged 9 ∼ 14 (10.8 ± 1.7) years, who were successfully corrected after intermittent exotropia surgery at the Beijing Tongren Hospital Affiliated to Capital Medical University from October 2023 to September 2023 were collected, the follow-up duration was six-month or longer. Paired t test, Pearson correlation analysis and multivariable linear regression analysis were used to probe preoperative clinical features that may predict the stereopsis six months after surgery. RESULTS: Six months after surgery, the angle of deviation of the patients met the orthotopic standard, and there was significant difference compared with that before surgery (distant: -2.7△±3.2△ vs. -30.5△±8.4△, t=-25.3, P < 0.001. Near:-3.7△±4.1△ vs. -33.7△±8.0△, t=-26.1, P < 0.001). Distant stereopsis (3.0 ± 0.6 vs. 3.9 ± 0.4, t = 4.9, P < 0.05) and near stereopsis (2.3 ± 0.5 vs. 2.6 ± 0.4, t = 3.8, P < 0.05) were both significantly improved compared with that of before surgery. 17% and 22% patients rebuilt normal distant stereopsis and normal near stereopsis, respectively. Preoperative distant stereopsis (r=-0.26, P = 0.004) and near stereopsis (r=-0.23, P = 0.011) was significantly negatively correlated with convergence reserve. Multivariable analysis showed that patients' age (ß = 0.003, p = 0.037), anisometropia (ß = 0.015, p = 0.043), and preoperative distant stereopsis (ß = 0.456, p < 0.001) were significantly associated with postoperative distant stereopsis. Patients' age (ß = 0.005, p = 0.044), anisometropia (ß = 0.127, p = 0.034), angle of deviation (ß=-0.230, p = 0.020), and preoperative near stereopsis (ß = 0.136, p < 0.001) were significantly associated with postoperative near stereopsis. CONCLUSION: IXT patients could get eye position fixed after surgery, about 20% patients benefited from stereopsis improvement. Patient's age, binocular anisometropia, angle of deviation and preoperative stereopsis were independent factors influencing postoperative stereopsis.

Alteration of Neurotrophic Factors and Innervation in Extraocular Muscles of Individuals With Concomitant Esotropia.

Purpose: To determine whether neurotrophic factors and innervation in extraocular muscles (EOMs) were altered in different types of concomitant esotropia, and to explore the possible association between neurotrophic factors and innervation of EOMs in humans. Methods: Patients with concomitant esotropia who required strabismus surgery were recruited from January to December 2022. Lateral rectus EOMs were obtained from patients, and controls were obtained from deceased organ donors. Immunofluorescence (IF) was performed to detect innervation of EOMs (neurofilament and synaptophysin), and immunohistochemistry (IHC) was used to detect the neurotrophic factors insulin-like growth factor-1 (IGF-1), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), and neurotrophin-3 (NT-3). The positive IHC results were further verified using western blotting (WB). One-way ANOVA followed by a Dunnett's multiple comparison post hoc test was used for continuous variables and the χ2 test for categorical variables. Spearman correlation analysis was used for the correlation analysis. Results: We collected lateral rectus EOM samples from acute and chronic types of concomitant esotropia and controls. Consistent with IHC, WB showed that IGF-1 was significantly increased in patients with acute acquired comitant esotropia or essential infantile esotropia compared with controls. In IF, synaptophysins were significantly increased only in acute acquired comitant esotropia compared with controls. Furthermore, Spearman correlation analysis showed that the correlation between IGF-1 and synaptophysin was borderline (P = 0.057) for patients with acute acquired comitant esotropia. Conclusions: Our study highlights the role of IGF-1 and altered innervation of EOMs in acute acquired comitant esotropia, suggesting that an effect of increased IGF-1 on nerve innervation may temporarily cause a compensatory increase in the strength of lateral rectus muscles.

The accuracy of different calculation methods when identifying handgrip strength asymmetry among middle-aged and older Chinese adults.

At present, there is no uniform standard mean of identifying handgrip strength (HGS) asymmetry based on maximum or average HGS values. Therefore, this study aimed to explore the accuracy of different calculation methods in the evaluation of HGS asymmetry. Using the maximum reading of two trials from both hands (Method A) as the reference standard, the accuracy of the HGS asymmetry identified by the average value of two trials of both hands (Method B) was determined by using various indicators, including specificity, sensitivity, the area under the receiver operating characteristic curve (AUC), positive, and negative predictive values. Overall, 12,163 individuals were included in this study, of whom 47.61% (5791/12,163) were male. The percentages of individuals with HGS asymmetry differed as a function of age and sex when using these two different methods. When employing Method A, 38.52%, 41.57%, and 44.57% of males 45 ≤ age<60, 60 ≤ age<80, and ≥ 80 years of age exhibited HGS asymmetry as compared to 40.78%, 39%, and 39.63% of females. Using Method B, the corresponding proportions were 41.69%, 42.5%, and 40% in males and 42.01%, 41.18%, and 40.55% in females, respectively. When compared to Method A, Method B was found to be effective in identifying HGS asymmetry, with AUC values ranging from 0.844 to 0.877. However, there was only moderate agreement between the two methods in assessing HGS asymmetry. Specifically, the Kappa values for the two Methods were 0.692, 0.694, and 0.766 in males aged 45 to 60, 60 to 80, and 80 years and above, respectively. For females, the Kappa values were 0.674, 0.661, and 0.751, respectively. These results demonstrated that the maximal or average HGS values from two trials using both hands has a significant impact on the consequent identification of HGS asymmetry.

Naphthalimide-based fluorescent probe for Hg2+ detection and imaging in living cells and zebrafish.

A simple naphthalimide-based fluorescent probe was designed and synthesized for the determination of mercury ion (Hg2+ ). The probe showed a noticeable fluorescence quenching response for Hg2+ . When added with Hg2+ , the fluorescence intensity of the probe at 560 nm was remarkably decreased with the color changed from yellow to colorless under ultraviolet (UV) light. The probe had a notable selectivity and sensitivity for Hg2+ and displayed an excellent sensing performance when detecting Hg2+ at low concentration (19.5 nM). The binding phenomenon between the probe and Hg2+ was identified by Job's method and high-resolution mass spectrometry (HRMS). Moreover, the probe was not only utilized to identify Hg2+ in real samples with satisfactory results (92.00%-110.00%) but also was successfully used for bioimaging in cells and zebrafish. The recognition mechanism has been verified by transmission electron microscopy (TEM) for the first time. All the results showed that the probe could be used as a potent useful tool for detection of Hg2+ .

Regulating TKT activity inhibits proliferation of human acute lymphoblastic leukemia cells.

Among pediatric blood cancers, acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy. Within ALL, T-cell acute lymphoblastic leukemia (T-ALL) accounts for 10 to 15% of all pediatric cases, and ~25% of adult cases. For T-ALL, its recurrence and relapse after treatment remain problematic. Therefore, it is necessary to develop new therapies for T-ALL. Recent studies suggested regulating energy metabolism is a novel approach to inhibit tumor growth, likely a promising treatment. Transketolase (TKT) is an important enzyme for modulating glucose metabolize in the pentose phosphate pathway (PPP). In this study, we treated T-ALL cells with different doses of niclosamide and primary T-ALL PBMCs were analyzed by RNA sequencing. T-ALL cells treated with niclosamide were analyzed with the Western blotting and TKT activity assay. Metabolism of T-ALL cells was evaluated by ATP assay and seahorse analyses. Lastly, we used a T-ALL xenograft murine model to determine effects of TKT knockdown on T-ALL tumor growth. Tumor samples were analyzed by H&E and IHC stainings. We found that niclosamide reduced T-ALL cell viability, and reduced expressions of TKT, Transketolase-Like Protein 1/2 (TKTL1/2) and transaldolase. In addition, niclosamide inhibited TKT enzyme activity, aerobic metabolism and glycolysis, finally leading to lower production of ATP. TKT knockdown inhibited tumor growth of xenograft T-ALL mice. Findings showed that niclosamide inhibits T-ALL cell growth by inhibiting TKT and energy metabolism.

Charge-Localized Retention and Long-Term Memory Enabled by Cooperating Sterically Confined Molecular Crystallization with Spiro[fluorene-9,9'-xanthene]-Based Csp3-Hindrance.

Charge localization of memory materials plays a crucial role in the endurance and retention ability of organic nonvolatile memory, which is completely opposite from the charge delocalization of high-mobility materials. However, charge transfer of both though-space and through-bond based on molecular design principles still faces challenges. Herein, a nonplanar wide-bandgap semiconductor with Csp3-hindrance (DOCH3-DDPA-SFX) has been designed and synthesized. An effective crystallization effect of self-assembled two-dimensional nanosheets on charge trapping dynamics and kinetics is visualized by Kelvin probe force microscopy (KPFM). The trapped charges are localized completely on a single nanosheet, which has better charge trapping and retention properties than an amorphous film. Meanwhile, crystallization also greatly improves structure stability. Combining DFT theoretical calculations, the mechanisms of localization and long-term retention are discussed. The steric crystallization effects on the charge localization will guide the effective design of single-component semiconducting charge-memory materials by molecular assembly and aggregate control for high-performance organic memory.