A nomogram for predicting food allergy in infants with feeding problems and malnutrition.

BACKGROUND AND OBJECTIVE: As oral food challenge (OFC) cannot be performed routinely in the general outpatient, this study aimed to construct a nomogram to predict the odds of food allergy in infants with idiopathic feeding problems and malnutrition. METHODS: From August 2018 to December 2021, 289 infants (median age, 6 months; P25-P75, 4-8) with idiopathic feeding problems and malnutrition were enrolled from seven hospitals in Shanghai, China. Food allergy was defined as a positive response to a skin prick test or OFC, with gastrointestinal, dermatologic, or respiratory symptom improvement after 4 weeks of avoidance of the suspected food. Demographic characteristics, Cow's Milk-related Symptom Scores (CoMiSS), and blood eosinophil amounts were evaluated for their associations with food allergy. Multivariable logistic regression analysis was used to identify variables to develop a nomogram model with the bootstrapped-concordance index as an assessment metric. RESULTS: Totally 249 of 289 infants had food allergy (86.2%). After logistic regression analysis, the feeding pattern (odds ratio [OR] = 5.28, 95% confidence interval [CI]: 2.13-13.09), a family history of allergy (OR = 1.79, 95% CI: 0.71-4.51), CoMiSS (OR = 1.45, 95% CI: 1.19-1.77), and eosinophil percentage (OR = 1.33, 95% CI: 1.11-1.60) were used to develop the model, which had a good performance with an area under the curve of 0.868 (95% CI: 0.792-0.944) and a bootstrapped-concordance index of 0.868. CONCLUSION: Food allergy is common in infants with idiopathic feeding problems and malnutrition. The developed nomogram may help identify infants with food allergy for further diagnosis.

Clinical and genetic characteristics of CEL-MODY (MODY8): a literature review and screening in Chinese individuals diagnosed with early-onset type 2 diabetes.

OBJECTIVE: CEL-related maturity-onset diabetes of the young (CEL-MODY, MODY8) is a special type of monogenetic diabetes caused by mutations in the carboxyl-ester lipase (CEL) gene. This study aimed to summarize the genetic and clinical characteristics of CEL-MODY patients and to determine the prevalence of the disease among Chinese patients with early-onset type 2 diabetes (EOD). METHODS: We systematically reviewed the literature associated with CEL-MODY in PubMed, Embase, Web of Science, China National Knowledge Infrastructure and Wanfang Data to analyze the features of patients with CEL-MODY. We screened and evaluated rare variants of the CEL gene in a cohort of 679 Chinese patients with EOD to estimate the prevalence of CEL-MODY in China. RESULTS: In total, 21 individuals reported in previous studies were diagnosed with CEL-MODY based on the combination of diabetes and pancreatic exocrine dysfunction as well as frameshift mutations in exon 11 of the CEL gene. CEL-MODY patients were nonobese and presented with exocrine pancreatic affection (e.g., chronic pancreatitis, low fecal elastase levels, pancreas atrophy and lipomatosis) followed by insulin-dependent diabetes. No carriers of CEL missense mutations were reported with exocrine pancreatic dysfunction. Sequencing of CEL in Chinese EOD patients led to the identification of the variant p.Val736Cysfs*22 in two patients. However, these patients could not be diagnosed with CEL-MODY because there were no signs that the exocrine pancreas was afflicted. CONCLUSION: CEL-MODY is a very rare disease caused by frameshift mutations affecting the proximal VNTR segments of the CEL gene. Signs of exocrine pancreatic dysfunction provide diagnostic clues for CEL-MODY, and genetic testing is vital for proper diagnosis. Further research in larger cohorts is needed to investigate the characteristics and prevalence of CEL-MODY in the Chinese population.

HBOT has a better cognitive outcome than NBH for patients with mild traumatic brain injury: A randomized controlled clinical trial.

BACKGROUND: Normobaric hyperoxia (NBH) and hyperbaric oxygen therapy (HBOT) are effective treatment plan for traumatic brain injury (TBI). The aim of this study was to compare cognitive outcome after mild TBI between NBH and HBOT so as to provide a more suitable treatment strategy for patients with mild TBI. METHODS: A prospective research was conducted between October 2017 and March 2023, enrolling patients with mild TBI (Glasgow coma scale score: 13-15 points) within 24 hours of injury in Cangzhou Central Hospital. Patients were randomized into 3 groups: group control (C), group NBH and group HBOT. The patients in HBOT group received hyperbaric oxygen therapy in high pressure oxygen chamber and patients in NBH group received hyperbaric oxygen therapy. at 0 minute before NBH or HBOT (T1), 0 minute after NBH or HBOT (T2) and 30 days after NBH or HBOT (T3), level of S100ß, NSE, GFAP, HIF-1α, and MDA were determined by ELISA. At the same time, the detection was performed for MoCA and MMSE scores, along with rSO2. RESULTS: The results showed both NBH and HBOT could improve the score of MoCA and MMSE, as well as the decrease the level of S100ß, NSE, GFAP, HIF-1α, MDA, and rSO2 compared with group C. Furthermore, the patients in group HBOT have higher score of MoCA and MMSE and lower level of S100ß, NSE, GFAP, HIF-1α, MDA, and rSO2. CONCLUSION: Both NBH and HBOT can effectively improve cognitive outcome for patients with mild TBI by improving cerebral hypoxia and alleviating brain injury, while HBOT exert better effect than NBH.

Prevalence and Clinical Characteristics of PDX1 Variant Induced Diabetes in Chinese Early-Onset Type 2 Diabetes.

CONTEXT: Maturity-onset diabetes of the young 4 (MODY4) is caused by mutations of PDX1; its prevalence and clinical features are not well known. OBJECTIVE: This study aimed to investigate the prevalence and clinical characteristics of MODY4 in Chinese people clinically diagnosed with early-onset type 2 diabetes (EOD), and to evaluate the relationship between the PDX1 genotype and the clinical phenotype. METHOD: The study cohort consisted of 679 patients with EOD. PDX1 mutations were screened by DNA sequencing, and their pathogenicity was evaluated by functional experiments and American College of Medical Genetics and Genomics guidelines. MODY4 was diagnosed in individuals with diabetes who carry a pathogenic or likely pathogenic PDX1 variant. All reported cases were reviewed for analyzing the genotype-phenotype relationship. RESULT: 4 patients with MODY4 were identified, representing 0.59% of this Chinese EOD cohort. All the patients were diagnosed before 35 years old, either obese or not obese. Combined with previously reported cases, the analysis revealed that the carriers of homeodomain variants were diagnosed earlier than those with transactivation domain variants (26.10 ± 11.00 vs 41.85 ± 14.66 years old, P < .001), and the proportions of overweight and obese individuals with missense mutation were higher than those with nonsense or frameshift mutations (27/34 [79.4%] vs 3/8 [37.5%], P = .031). CONCLUSION: Our study suggested that MODY4 was prevalent in 0.59% of patients with EOD in a Chinese population. It was more difficult to identify clinically than other MODY subtypes owning to its clinical similarity to EOD. Also, this study revealed that there is some relationship between genotype and phenotype.

Efficient Evaluation of Concrete Fracture Surface Roughness Using Fringe Projection Technology.

The evaluation of concrete surface roughness is crucial in the field of civil engineering. The purpose of this study is to propose a no-contact and efficient method for the measurement of the roughness of concrete fracture surfaces based on fringe-projection technology. A simple phase-correction method using one additional strip image is presented for the phase unwrapping to improve the measurement efficiency and accuracy. The experimental results indicate that the measuring error for plane height is less than 0.1mm, and the relative accuracy for measuring a cylindrical object is about 0.1%, meeting the requirements for concrete fracture-surface measurement. On this basis, three-dimensional reconstructions were carried out on various concrete fracture surfaces to evaluate the roughness. The results reveal that the surface roughness (R) and fractal dimension (D) decrease as the concrete strength increases or the water-to-cement ratio decreases, consistent with previous studies. In addition, compared with the surface roughness, the fractal dimension is more sensitive to the change in concrete surface shape. The proposed method is effective for detecting concrete fracture-surface features.

To explore the change of motor cognitive function in pituitary tumor rats after operation.

To study the changes of motor and cognitive function of pituitary tumor rats after the operation. Methods: The experiment was divided into three groups: control group, model group and operation group (30 animals for each group). Female Fischer344 rats were selected. Model group rats were subcutaneously embedded with 10 mg estrogen sustained-release pump to induce a pituitary tumor model, and control group rats were subcutaneously embedded with a normal saline sustained-release pump as control. The operation group was successfully treated by microsurgery after the model was established. The quantitative expressions of PTTG, FGF-2 and VEGF were detected by Western blot. Morris test was used to detect the spatial learning and memory ability of rats. Western blot results showed that compared with the model group, the expression of the operation group was decreased, but still higher than that of the control group (p < 0.05). The water maze test results showed that the incubation period of searching the safe island in the model group was significantly longer than that in the control group on the 8th and 9th day after the injury, and the difference was statistically significant (p < 0.05). The incubation period of searching the safe island on the 8th and 9th day after injury in the operation group was significantly shorter than that in the control group. Through the detection of behavioral-related experimental and protein, the motor memory of rats after pituitary tumor surgery can be improved to some extent.

Maternal and neonatal blood vitamin D status and neurodevelopment at 24 months of age: a prospective birth cohort study.

BACKGROUND: This study aimed to explore the relationship of 25-hydroxyvitamin D [25(OH)D] in three trimesters and at birth with neurodevelopment at 24 months of age. METHODS: From 2013 to 2016, pregnant women from the Shanghai Birth Cohort in China were recruited for the study. Altogether, 649 mother-infant pairs were included. Serum 25(OH)D was measured with mass spectrometry in three trimesters, and cord blood was divided into deficiency (< 20 and < 12 ng/mL, respectively), insufficiency (20-30 and 12-20 ng/mL, respectively), and sufficiency (≥ 30 and ≥ 20 ng/mL, respectively). Bayley-III scale was used to assess cognitive, language, motor, social-emotional, and adaptive behavior development at 24 months of age. The Bayley-III scores were grouped into quartiles, and scores within the lowest quartile were defined as suboptimal development. RESULTS: After adjusting for confounding factors, cord blood 25(OH)D in the sufficient group was positively correlated with cognitive [ß = 11.43, 95% confidence interval (CI) = 5.65-17.22], language (ß = 6.01, 95% CI = 1.67-10.3), and motor scores (ß = 6.43, 95% CI = 1.73-11.1); cord blood 25(OH)D in the insufficient group was also positively correlated with cognitive scores (ß = 9.42, 95% CI = 3.74-15.11). Additionally, sufficient vitamin D status in the four periods and persistent 25(OH)D ≥ 30 ng/mL throughout pregnancy were associated with a lower risk of suboptimal cognitive development in adjusted models, although the effects were attenuated after applying the false discovery rate adjustment. CONCLUSIONS: Cord blood 25(OH)D ≥ 12 ng/mL has a significant positive association with cognitive, language, and motor development at 24 months of age. Sufficient vitamin D status in pregnancy might be a protective factor for suboptimal neurocognition development at 24 months of age.

Lead acetate induces cartilage defects and bone loss in zebrafish embryos by disrupting the GH/IGF-1 axis.

Skeletal system toxicity due to lead exposure has attracted extensive attention in recent years, but few studies focus on the skeletal toxicity of lead in the early life stages of zebrafish. The endocrine system, especially the GH/IGF-1 axis, plays an important role in bone development and bone health of zebrafish in the early life. In the present study, we investigated whether lead acetate (PbAc) affected the GH/IGF-1 axis, thereby causing skeletal toxicity in zebrafish embryos. Zebrafish embryos were exposed to lead PbAc between 2 and 120 h post fertilization (hpf). At 120 hpf, we measured developmental indices, such as survival, deformity, heart rate, and body length, and assessed skeletal development by Alcian Blue and Alizarin Red staining and the expression levels of bone-related genes. The levels of GH and IGF-1 and the expression levels of GH/IGF-1 axis-related genes were also detected. Our data showed that the LC50 of PbAc for 120 h was 41 mg/L. Compared with the control group (0 mg/L PbAc), after PbAc exposure, the deformity rate increased, the heart rate decreased, and the body length was shortened at various time periods, in the 20-mg/L group at 120 hpf, the deformity rate increased by 50 fold, the heart rate decreased by 34%, and the body length shortened by 17%. PbAc altered cartilage structures and exacerbated bone loss in zebrafish embryos; in addition, PbAc exposure down-regulated the expression of chondrocyte (sox9a, sox9b), osteoblast (bmp2, runx2) and bone mineralization-related genes (sparc, bglap), and up-regulated the expression of osteoclast marker genes (rankl, mcsf). The GH level increased and the IGF-1 level declined significantly. The GH/IGF-1 axis related genes (ghra, ghrb, igf1ra, igf1rb, igf2r, igfbp2a, igfbp3, igfbp5b) were all decreased. These results suggested that PbAc inhibited the differentiation and maturation of osteoblasts and cartilage matrix, promoted the formation of osteoclasts, and ultimately induced cartilage defects and bone loss by disrupting the GH/IGF-1 axis.

Association between Suboptimal 25-Hydroxyvitamin D Status and Overweight/Obesity in Infants: A Prospective Cohort Study in China.

This study aimed to investigate whether 25-hydroxyvitamin D (25(OH)D) concentrations are correlated to overweight/obesity in infants and to explore a threshold of 25(OH)D. A total of 1205 six-month-old infants from two community hospitals in Shanghai were randomly recruited, and 925 of them were followed up at 12 months. Concentration of 25(OH)D, weight, and length were measured at two time points. Overweight/obesity was defined as a weight-for-length Z-score >97th percentile. The prevalence of overweight/obesity at 6 and 12 months was 6.88% and 5.26%, respectively. The occurrence of vitamin D (VitD) deficiency (<20 ng/mL) at 6 and 12 months was 6.56% and 2.05%, respectively. Concentration of 25(OH)D at the corresponding age was negatively associated with weight-for-length percentile (WLP) at both 6 (adjusted ß: −0.14; 95% CI: −0.27, −0.02; p = 0.02) and 12 months (adjusted ß: −0.22; 95% CI: −0.41, −0.02; p = 0.03), while the relationship between 25(OH)D at 6 months and WLP at 12 months was nonlinear, where 35 ng/mL was identified as an inflection point. Those with a concentration of 25(OH)D <35 ng/mL at 6 months had a higher risk of overweight/obesity (adjusted OR: 1.42; 95% CI: 1.06, 1.91; p = 0.02) compared to the group with a concentration of 25(OH)D ≥35 ng/mL. Moreover, a concentration of 25(OH)D <35 ng/mL at two time points significantly increased the risk of overweight/obesity at 12 months compared to the group with 25(OH)D concentration ≥35 ng/mL at two time points (adjusted OR: 2.91; 95% CI: 1.13, 7.46; p = 0.03). A suboptimal 25(OH)D concentration <35 ng/mL significantly increases the risk of overweight/obesity in infants.

Solar Boosting Pollutant Removal plus Hydrogen Production by Lifting-Heat and Lowering-Potential Chemical Synergy.

Solar-boosted oxidation plus hydrogen production for pollutant removal in wastewater, driven by a high thermal and low-potential electrochemical combination, is facilitated and demonstrated from theory to experiments. One sun fully offers both thermal and electrical energy powered thermo- and electrochemistry for pollutant oxidation. Solar thermal action provides high temperatures for the activation of the pollutant molecules to gear up for solar-driven electrochemical oxidation. Taking wastewater containing phenol as an example, the cyclic voltammetry (CV) curves display two redox processes at less than 100 °C, while only one redox process of single oxidation of phenol appears at more than 100 °C. The oxidation of phenol is accompanied by an efficient evolution of hydrogen, in which the yield of 0.627 mL at 30 °C is increased to 2.294 mL at 210 °C. The phenol removal is enhanced to 80.50% at 210 °C. Tracking the reaction progress shows that small molecular organic acids are detected as the only intermediate at the high temperatures, which suggests the easy realization of full mineralization. The kinetic reaction of the phenol oxidation is fitted to the first order with an increase of the rate constant of 10 times compared with that at low temperatures. Solar engineering of oxidation of organic pollutants not only solves the issue of energy demand for the tough wastewater treatment but also realizes fast and efficient oxidation of organic pollutants. This study opens up new avenues to achieve solar wastewater treatment and simultaneous hydrogen production.

Nanocrystals with metastable high-pressure phases under ambient conditions.

The ambient metastability of the rock-salt phase in well-defined model systems comprising nanospheres or nanorods of cadmium selenide, cadmium sulfide, or both was investigated as a function of composition, initial crystal phase, particle structure, shape, surface functionalization, and ordering level of their assemblies. Our experiments show that these nanocrystal systems exhibit ligand-tailorable reversibility in the rock salt-to-zinc blende solid-phase transformation. Interparticle sintering was used to engineer kinetic barriers in the phase transformation to produce ambient-pressure metastable rock-salt structures in a controllable manner. Interconnected nanocrystal networks were identified as an essential structure that hosted metastable high-energy phases at ambient conditions. These findings suggest general rules for transformation-barrier engineering that are useful in the rational design of next-generation materials.

Chemotherapy of Capecitabine plus Temozolomide for Refractory Pituitary Adenoma after Tumor Resection and Its Impact on Serum Prolactin, IGF-1, and Growth Hormone.

Objective: To investigate the efficiency of capecitabine (CAP) plus temozolomide (TEM) in refractory pituitary adenoma after tumor resection and its impact on serum prolactin (PRL), insulin-like growth factor 1 (IGF-1), and growth hormone (GH) levels. Methods: From January 2017 to January 2020, 80 patients assessed for eligibility receiving transsphenoidal tumor resection for refractory pituitary adenoma in the Department of Neurosurgery of our hospital were recruited. They were randomly distributed at a ratio of 1 : 1 via the random number table method to receive either bromocriptine and TEM (control group) or bromocriptine plus combination chemotherapy of TEM and CAP (study group). The two groups were compared in terms of clinical efficacy and serum levels of PRL, IGF-1, and GH. Results: The objective response rate (ORR) was 87.50% and 67.50% in the study group and the control group, respectively (P=0.032). Before treatment, two groups had similar levels of PRL, IGF-1, and GH. After treatment, PRL levels in the study group were lower than that in the control group (278.35 ± 39.25 versus 326.35 ± 42.45, P < 0.001). Compared with the control group, IGF-1 levels in the study group were also lower (311.78 ± 28.82 versus 364.35 ± 31.35, P < 0.001). The study group presented markedly lower levels of thyroid-stimulating hormone (TSH) and higher serum levels of free thyroxine-4 (FT-4) and adrenocorticotropic hormone (ACTH) versus the control group (P < 0.05). The incidence of adverse events was comparable between the study group (30.0%) and the control group (22.5%) (P > 0.05). All eligible patients had similar progression-free survival (PFS) after chemotherapy. Conclusion: For patients with refractory pituitary adenoma, the combination chemotherapy of CAP and TEM significantly improves clinical outcomes and corrects hormonal disturbances, with a good safety profile, but its long-term efficacy requires further investigation.

Unconventional Hysteretic Transition in a Charge Density Wave.

Hysteresis underlies a large number of phase transitions in solids, giving rise to exotic metastable states that are otherwise inaccessible. Here, we report an unconventional hysteretic transition in a quasi-2D material, EuTe_{4}. By combining transport, photoemission, diffraction, and x-ray absorption measurements, we observe that the hysteresis loop has a temperature width of more than 400 K, setting a record among crystalline solids. The transition has an origin distinct from known mechanisms, lying entirely within the incommensurate charge density wave (CDW) phase of EuTe_{4} with no change in the CDW modulation periodicity. We interpret the hysteresis as an unusual switching of the relative CDW phases in different layers, a phenomenon unique to quasi-2D compounds that is not present in either purely 2D or strongly coupled 3D systems. Our findings challenge the established theories on metastable states in density wave systems, pushing the boundary of understanding hysteretic transitions in a broken-symmetry state.

Model-free robust adaptive integral sliding mode impedance control of knee-ankle-toe active transfemoral prosthesis.

BACKGROUND: Wearing appropriate active prosthesis is the guarantee of daily life for amputees. Normally the controller of the traditional active transfemoral prosthesis is designed based on the mathematical model. The modelling error and the external interference will reduce the control accuracy of the system and make the prosthesis unable to operate in the desired trajectory. METHODS: Firstly, combined with time delay estimation (TDE), a model-free robust integral sliding mode impedance controller is designed. This method not only suppress the impedance error, but also eliminate the nonlinear relationship and disturbance in the dynamic model. Secondly, an adaptive law is proposed to update the controller gain, which provide stable control effect. Thirdly, the stability of prosthesis closed-loop system is proved by Lyapunov stability theory. Finally, the motor torque is used to drive each joint, and Matlab/Simscape is used to verify the prosthesis control system. RESULTS: From the result of the simulation experiment, the control method has a good tracking effect on each joint. The root mean square error and mean absolute errors of each joint's angle tracking error are 0.6123°, 1.9976°, 0.5574° and 0.2635°, 1.8175°, 0.4796°. Compared with the controller without adaptive gain and impedance control, the control effect is improved, and the plantar pressure of amputees is closer to the sound side. CONCLUSIONS: Comparing the results of different controllers, the adaptive integral sliding mode impedance controller with TDE can better track the expected angles of each joint. The gait is more normal. The walking performance of the prosthesis wearers is improved.

Interfacial ferroelectricity in rhombohedral-stacked bilayer transition metal dichalcogenides.

van der Waals materials have greatly expanded our design space of heterostructures by allowing individual layers to be stacked at non-equilibrium configurations, for example via control of the twist angle. Such heterostructures not only combine characteristics of the individual building blocks, but can also exhibit physical properties absent in the parent compounds through interlayer interactions1. Here we report on a new family of nanometre-thick, two-dimensional (2D) ferroelectric semiconductors, where the individual constituents are well-studied non-ferroelectric monolayer transition metal dichalcogenides (TMDs), namely WSe2, MoSe2, WS2 and MoS2. By stacking two identical monolayer TMDs in parallel, we obtain electrically switchable rhombohedral-stacking configurations, with out-of-plane polarization that is flipped by in-plane sliding motion. Fabricating nearly parallel-stacked bilayers enables the visualization of moiré ferroelectric domains as well as electric field-induced domain wall motion with piezoelectric force microscopy. Furthermore, by using a nearby graphene electronic sensor in a ferroelectric field transistor geometry, we quantify the ferroelectric built-in interlayer potential, in good agreement with first-principles calculations. The new semiconducting ferroelectric properties of these four new TMDs opens up the possibility of studying the interplay between ferroelectricity and their rich electric and optical properties2-5.

Role of Equilibrium Fluctuations in Light-Induced Order.

Engineering novel states of matter with light is at the forefront of materials research. An intensely studied direction is to realize broken-symmetry phases that are "hidden" under equilibrium conditions but can be unleashed by an ultrashort laser pulse. Despite a plethora of experimental discoveries, the nature of these orders and how they transiently appear remain unclear. To this end, we investigate a nonequilibrium charge density wave (CDW) in rare-earth tritellurides, which is suppressed in equilibrium but emerges after photoexcitation. Using a pump-pump-probe protocol implemented in ultrafast electron diffraction, we demonstrate that the light-induced CDW consists solely of order parameter fluctuations, which bear striking similarities to critical fluctuations in equilibrium despite differences in the length scale. By calculating the dynamics of CDW fluctuations in a nonperturbative model, we further show that the strength of the light-induced order is governed by the amplitude of equilibrium fluctuations. These findings highlight photoinduced fluctuations as an important ingredient for the emergence of transient orders out of equilibrium. Our results further suggest that materials with strong fluctuations in equilibrium are promising platforms to host hidden orders after laser excitation.

Relatively low tooth replacement rate in a sauropod dinosaur from the Early Cretaceous Ruyang Basin of central China.

Tooth replacement rate is an important feature related to feeding mechanics and food choices for dinosaurs. However, only a few data points are available for sauropod dinosaurs, partially due to rarity of relevant fossil material. Four somphospondylan sauropod species have been recovered from the Lower Cretaceous Aptian-Albian Haoling Formation in the Ruyang Basin, Henan Province of central China, but no cranial material has been reported except for a single crown. Here we report the discovery of the rostral portion of a left dentary with replacement teeth in its first five alveoli. Comparative anatomical study shows the partial dentary can be assigned to a member of early diverging somphospondylans. The non-destructive tooth length-based approach to estimating tooth formation time and replacement rate is adopted here. The estimated tooth replacement rate is 76 days, faster than that of Brachiosaurus (83 days) and much lower than typical late diverging lithostrotian titanosaurians (20 days). Thus, this discovery adds an intermediate tooth replacement rate in the evolution of titanosauriform sauropods and supports the idea that evolution of tooth replacement rate is clade-specific. This discovery also provides more information to understand the Ruyang sauropod assemblage, which includes one of the most giant dinosaurs to have walked our Earth (Ruyangosaurus giganteus).

Synthesis of Novel Pinocembrin Amino Acid Derivatives and Their Antiaging Effect on Caenorhabditis elegans via the Modulating DAF-16/FOXO.

PURPOSE: Pinocembrin is a dihydroflavonoid, which is widely found in several plant species. Although pinocembrin has good pharmacological activity, it has poor water solubility and low bioavailability. Therefore, we have modified the structure of pinocembrin with a combination of different amino acids to solve this problem. Moreover, the effect of the antiaging activity of them has not been explored. We aim to investigate the effect of pinocembrin and its amino acid derivatives on the aging of Caenorhabditis elegans. METHODS: Pinocembrin was spliced with different amino acids in order to obtain their corresponding derivatives. The preliminary research of pinocembrin and its amino acid derivatives on antiaging effect was studied by using the C. elegans model. Among all the compounds, the one shows the best antiaging effect was then studied on antiaging mechanism. The protective effect on nematodes under emergency conditions was explained by detecting the ROS content and sod-3p::GFP fusion protein expression in nematodes; the possible anti-aging mechanism of nematodes was determined by DAF-16 nuclear localization experiment and the survival curve of transgenic nematodes model under stress conditions. RESULTS: Pb-3 showed the best effect on increasing tolerance to thermal and oxidative stress and reduce the accumulation of lipofuscin. In the assay of C. elegans, pb-3 reduced intracellular ROS accumulation. Application of pb-3 to the transgenic mutant TJ356 induced the translocation of the transcription factor DAF-16 from the cytosol to the nucleus, and modulated the expression of SOD-3 (downstream genes of daf-16), which regulates longevity in C. elegans. Moreover, pb-3 did not prolong the lifespan of daf-16, age-1, daf-2 and hsp16.2 mutants, suggesting that these genetic pathways are involved in mediating the antiaging effects of pb-3. CONCLUSION: The antioxidant and antiaging properties of pb-3 may involve in the DAF-16/FOXO transcription process. Pinocembrin amino acid derivatives might be a novel agent for antiaging therapy.

A versatile sample fabrication method for ultrafast electron diffraction.

Integral to the exploration of nonequilibrium phenomena in solid-state systems is the study of lattice motion after photoexcitation by a femtosecond laser pulse. For the past two decades, ultrafast electron diffraction (UED) has played a critical role in this regard. Despite remarkable progress in instrumental development, this technique is still bottlenecked by a demanding sample preparation process, where ultrathin single crystals of large lateral size are typically required. In this work, we describe an efficient, versatile method that yields high-quality, laterally extended (≥ 100 µm), and thin (≤ 50 nm) single crystals on amorphous films of Si3N4 windows. It applies to most exfoliable materials, including those reactive in ambient conditions, and promises clean, flat surfaces. Besides the natural extension to fabricating van der Waals heterostructures, our method can also be applied to future-generation UED that enables additional control of sample parameters, such as electrostatic gating and excitation by a locally enhanced terahertz field. Our work significantly expands the type of samples for UED studies and also finds application in other time-resolved techniques such as attosecond extreme-ultraviolet absorption spectroscopy. This method hence provides further opportunities to explore photoinduced transitions and to discover novel states of matter out of equilibrium.

Cudraxanthone L inhibits gastric cancer by regulating the MAPK signalling and promoting FAS-mediated pathway.

Gastric cancer (GC) is one of the most common malignancies and has the second highest lethal rate in the world; thus, finding new medicines with high potency and low toxicity is urgent. Cudrania tricuspidata (Carr.) Bur. ex Lavallee (Moraceae) is a traditional medicinal herb that is considered to have antitumour efficacy. We extracted and isolated cudraxanthone L (CXL) from Cudrania tricuspidata and evaluated its anti-cancer efficacy. CXL treatment inhibited angiogenesis of chorioallantoic membrane (CAM) and repressed the cell viability of various human cancer cells, indicating it presented the antitumour potential. Among them, CXL presented the best inhibitory effects on MGC803 cells. In addition, the invasion, migration and clonogenicity were significantly repressed, S phase of the cell cycle was arrested, and apoptosis was induced when MGC803 cells were treated with CXL. The results of RNA sequencing, qRT-PCR and western blotting verified that CXL regulated the MAPK signalling pathway and induced apoptosis by FAS-mediated pathway. The in vivo data revealed that CXL arrested tumour growth without toxic effects and upregulated the protein levels in FAS-mediated pathway in MGC803 gastric cancer-bearing mice. In summary, we demonstrate CXL presents impactful anti-GC efficacy by regulating the MAPK signalling pathway and promoting the FAS-mediated pathway.