The Role of the Medial Prefrontal Cortex in Spatial Margin of Safety Calculations.

Naturalistic observations show that animals pre-empt danger by moving to locations that increase their success in avoiding future threats. To test this in humans, we created a spatial margin of safety (MOS) decision task that quantifies pre-emptive avoidance by measuring the distance subjects place themselves to safety when facing different threats whose attack locations vary in predictability. Behavioral results show that human participants place themselves closer to safe locations when facing threats that attack in spatial locations with more outliers. Using both univariate and multivariate pattern analysis (MVPA) on fMRI data collected during a 2 h session on participants of both sexes, we demonstrate a dissociable role for the vmPFC in MOS-related decision-making. MVPA results revealed that the posterior vmPFC encoded for more unpredictable threats with univariate analyses showing a functional coupling with the amygdala and hippocampus. Conversely, the anterior vmPFC was more active for the more predictable attacks and showed coupling with the striatum. Our findings converge in showing that during pre-emptive danger, the anterior vmPFC may provide a safety signal, possibly via foreseeable outcomes, while the posterior vmPFC drives unpredictable danger signals.

2 in. Bulk ß-Ga2O3 Single Crystals Grown by EFG Method with High Wafer-Scale Quality.

2 in. bulk ß-Ga2O3 single crystals are successfully grown by the edge-defined film-fed growth method with a homemade furnace system. By considering the significance of wafer quality in future mass manufacture, a nine-point characterization method is developed to evaluate the full-scale quality of the processed 2 in. (100)-orientated ß-Ga2O3 single-crystal wafers. Crystalline and structural characteristics were evaluated using X-ray diffraction and Raman spectroscopy, revealing decent crystalline quality with a mean full width at half-maximum value of 60.8 arcsec and homogeneous bonding structures. The statistical root-mean-square surface roughness, determined from nine scanning areas, was found to be only 0.196 nm, indicating superior surface quality. Linear optical properties and defect levels were further investigated using UV-visible spectrophotometry and photoluminescence spectroscopy. The high wafer-scale quality of the processed ß-Ga2O3 wafers meets the requirements for homoepitaxial growth substrates in electronic and photonic devices with vertical configurations.

Self-Assembled Nanoparticles from the Amphiphilic Prodrug of Resiquimod for Improved Cancer Immunotherapy.

Tumor-associated macrophages (TAMs) usually adopt a tumor-promoting M2-like phenotype, which largely impedes the immune response and therapeutic efficacy of solid tumors. Repolarizing TAMs from M2 to the antitumor M1 phenotype is crucial for reshaping the tumor immunosuppressive microenvironment (TIME). Herein, we developed self-assembled nanoparticles from the polymeric prodrug of resiquimod (R848) to reprogram the TIME for robust cancer immunotherapy. The polymeric prodrug was constructed by conjugating the R848 derivative to terminal amino groups of the linear dendritic polymer composed of linear poly(ethylene glycol) and lysine dendrimer. The amphiphilic prodrug self-assembled into nanoparticles (PLRS) of around 35 nm with a spherical morphology. PLRS nanoparticles could be internalized by antigen-presenting cells (APCs) in vitro and thus efficiently repolarized macrophages from M2 to M1 and facilitated the maturation of APCs. In addition, PLRS significantly inhibited tumor growth in the 4T1 orthotopic breast cancer model with much lower systemic side effects. Mechanistic studies suggested that PLRS significantly stimulated the TIME by repolarizing TAMs into the M1 phenotype and increased the infiltration of cytotoxic T cells into the tumor. This study provides an effective polymeric prodrug-based strategy to improve the therapeutic efficacy of R848 in cancer immunotherapy.

Achieving Self-Reinforcing Triboelectric-Electromagnetic Hybrid Nanogenerator by Magnetocaloric and Magnetization Effects of Gadolinium.

Triboelectric-electromagnetic hybrid nanogenerator (TEHG) has emerged as a promising technology for distributed energy harvesting. However, currently reported hybrid generators are straightforward combinations of two functional components. Moreover, inevitable heat from friction intensifies material abrasion and degrades the performance of polymer-based triboelectric nanogenerators (TENGs). Here, a self-reinforcing TEHG (SR-TEHG) that harnesses the magnetocaloric and magnetization effects of gadolinium (Gd), is proposed. The synergy between TENG and electromagnetic generator (EMG) renders them an indivisible unit. Leveraging Gd's magnetocaloric effect, an efficient heat transfer mechanism is constructed to cool the tribolayer and strengthen the device's electrical stability. After 80 h of continuous operation, the optimized TENG occupies a charge decay rate of only 0.32% per hour, significantly outperforming most existing TENGs. Additionally, Gd's magnetization effect boosts the power of EMG by ≈80.84%. This work provides a universal solution in hybrid generators where internal components reinforce each other, achieving a synergistic effect of 1 + 1 > 2.

Highly sensitive and accurate detection of cholesterol based on a single red upconversion biosensor.

Cholesterol (CHOL) is an important clinical biochemical indicator that plays an important role in the regulation of the fluidity, permeability, and microstructure of cell membranes. Therefore, it is necessary to accurately monitor CHOL levels in biological samples for the early prevention and diagnosis of various diseases. The single-band red upconversion nanoparticle (UCNP) emits light within the optical transmission window of biological tissues, and can penetrate deeper biological tissues and cause less energy loss due to scattering and thus have higher sensitivity and accuracy. Here, using the nontoxic, sensitive, and photochemically stable 3,3',5,5'-tetramethylbenzidine (TMB) as the quenching agent and single red UCNP as the fluorescent donor, a dual-readout colorimetric and fluorescent sensor was developed to detect CHOL. The detection mechanism and feasibility were discussed in detail, and experimental conditions such as Fe2+ concentration, TMB concentration and reaction time were explored. Under optimal conditions, the limits of CHOL detection by colorimetry and fluorescence were 0.85 µM and 0.63 µM. The sensing system was used to measure CHOL in serum samples and the values obtained by these two modes were close, and the spiked recoveries were 97.2-102.2% and 97.1-103.7%, respectively, which holds great potential in clinical diagnosis and health management.

The mechanism of internal and external efficacy influences residents' pro-environmental behavior through environmental willingness.

The Chinese government's environmental conservation efforts require the active participation of all society. This study investigated how internal and external efficacy influence pro-environmental behavior with environmental willingness as a mediator. This study employed a structural equation model to analyze the data from 1499 survey questionnaires. The analysis revealed that both internal and external efficacy can enhance individuals' pro-environmental behavior in the private and public spheres. External efficacy has a stronger impact on environmental willingness and public sphere environmental behavior, while internal efficacy more significantly influences private sphere environmental behavior. Additionally, environmental willingness only mediates efficacy and public sphere environmental behavior. The innovation of this study is the examination of internal and external efficacy from the perspective of different sources and the comparison of their differential impacts on pro-environmental behavior. Relevant policies should effectively enhance residents' internal and external efficacy to comprehensively improve their level of pro-environmental behavior.

Detection of Porcine Circovirus Type 3 in Serum, Semen, Oral Fluid, and Preputial Fluid Samples of Boars.

Porcine circovirus type 3 (PCV3) is commonly associated with clinical symptoms such as porcine dermatitis and nephropathy syndrome (PDNS)-like lesions, respiratory signs, and reproductive disorders. This study aimed to investigate the epidemiology of PCV3 in a boar stud. The objectives were to detect PCV3 in semen, as well as matched serum, oral fluid, and preputial fluid samples from adult boars using quantitative polymerase chain reaction (qPCR), analyze PCV3-IgG antibody data, and genetically characterize a positive sample. A total of 112 samples from 28 boars were collected from a large-scale pig farm in Guangxi, China. The qPCR results showed that the PCV3 DNA was not detected in semen, with a positive rate of 0% (0/28), while it was detected in serum (3.57%-1/28), oral fluid (64.28%-18/28), and preputial fluid (46.4%-13/28). The seropositivity rate of PCV3-IgG in serum was 82.14% (23/28) according to the indirect enzyme-linked immunosorbent serologic assay (ELISA) results. Phylogenetic analysis revealed that one of the PCV3 isolates belonged to the PCV3c clades. This is the first report of PCV3 detection in preputial fluid from boars. The results suggest that PCV3 is transmitted among boars on pig farms and exhibits epidemic characteristics.

Apple Pomace Compositional Data Highlighting the Proportional Contribution of Polymeric Procyanidins.

Recent years have seen an increase in research focusing on the amelioration of apple pomace waste for use in the food and nutraceutical industries. Much of this work has concentrated on the characterisation of the polyphenol composition of apple pomace materials to determine their role in conferring nutritional and health benefits. Although apples contain substantial quantities of polymeric procyanidins (condensed tannins), this class of compounds has received limited attention in apple research. This study quantified the polymeric procyanidins in apple pomace extracts using a rapid, methyl-cellulose precipitation (MCP) approach for the first time. In addition, a non-targeted metabolomics approach was applied to determine the most abundant phenolic classes present. Polymeric procyanidins were found to be the most abundant type of polyphenol in apple pomace extracts and were generally oligomeric in nature. Multivariate statistical analysis revealed that the ferric-reducing antioxidant power (FRAP) was most strongly correlated with the polymeric procyanidin concentration. Noting that polymeric procyanidins may not cross the cell layer to exert antioxidant activity in vivo, their presence in apple pomace extracts may therefore overestimate the FRAP. This work highlights the importance of polymeric procyanidins in the phenolic diversity of apple pomaces, and it is proposed that in future studies, rapid MCP assays may be used for their quantification.

Nanomaterials for mRNA-based therapeutics: Challenges and opportunities.

Messenger RNA (mRNA) holds great potential in developing immunotherapy, protein replacement, and genome editing. In general, mRNA does not have the risk of being incorporated into the host genome and does not need to enter the nucleus for transfection, and it can be expressed even in nondividing cells. Therefore, mRNA-based therapeutics provide a promising strategy for clinical treatment. However, the efficient and safe delivery of mRNA remains a crucial constraint for the clinical application of mRNA therapeutics. Although the stability and tolerability of mRNA can be enhanced by directly retouching the mRNA structure, there is still an urgent need to improve the delivery of mRNA. Recently, significant progress has been made in nanobiotechnology, providing tools for developing mRNA nanocarriers. Nano-drug delivery system is directly used for loading, protecting, and releasing mRNA in the biological microenvironment and can be used to stimulate the translation of mRNA to develop effective intervention strategies. In the present review, we summarized the concept of emerging nanomaterials for mRNA delivery and the latest progress in enhancing the function of mRNA, primarily focusing on the role of exosomes in mRNA delivery. Moreover, we outlined its clinical applications so far. Finally, the key obstacles of mRNA nanocarriers are emphasized, and promising strategies to overcome these obstacles are proposed. Collectively, nano-design materials exert functions for specific mRNA applications, provide new perception for next-generation nanomaterials, and thus revolution of mRNA technology.

Stem Cell Therapies for Restorative Treatments of Central Nervous System Ischemia-Reperfusion Injury.

Ischemic damage to the central nervous system (CNS) is a catastrophic postoperative complication of aortic occlusion subsequent to cardiovascular surgery that can cause brain impairment and sometimes even paraplegia. Over recent years, numerous studies have investigated techniques for protecting and revascularizing the nervous system during intraoperative ischemia; however, owing to a lack of knowledge of the physiological distinctions between the brain and spinal cord, as well as the limited availability of testing techniques and treatments for ischemia-reperfusion injury, the cause of brain and spinal cord ischemia-reperfusion injury remains poorly understood, and no adequate response steps are currently available in the clinic. Given the limited ability of the CNS to repair itself, it is of great clinical value to make full use of the proliferative and differentiation potential of stem cells to repair nerves in degenerated and necrotic regions by stem cell transplantation or mobilization, thereby introducing a novel concept for the treatment of severe CNS ischemia-reperfusion injury. This review summarizes the most recent advances in stem cell therapy for ischemia-reperfusion injury in the brain and spinal cord, aiming to advance basic research and the clinical use of stem cell therapy as a promising treatment for this condition.

Impact of the established healthy canteens and restaurants in Shanghai on usage of oil， salt， and sugar， and on nutritional knowledge and behavior of diners / 上海预防医学

ObjectiveTo evaluate the changes of the usage of oil， salt， sugar and nutritional knowledge and behavior intervention among diners before and after the establishment of healthy canteens and restaurants in Shanghai. MethodsA comprehensive intervention was conducted through the establishment of healthy canteens and restaurants， encompassing interventions such as oil， salt， and sugar management， improvement of nutritional environment， staffing and training activities， and nutrition labeling guidance. A pre-post self-controlled study design was used to compare changes in oil， salt and sugar usage， as well as diners’ knowledge and behaviors related to nutrition and nutrition labeling， before and after the intervention. ResultsAfter intervention， the total usage of oil， salt， and sugar per meal in the canteens and restaurants decreased by 18.33%， 14.83%， and 13.66%， respectively，and all had statistically significance differences（P<0.001）. The awareness rate of "cooking oil intake"， "salt intake"， and "added sugar intake" among diners increased from 24.07% to 38.04%， 58.52% to 71.28%， and 26.85% to 45.01%， respectively. The awareness rate of "daily food types" and "weekly food types" increased from 43.07% to 56.53% and 49.52% to 64.32%， with significant differences （P<0.001）. The rate of understanding the content of nutrition labels increased from 66.91% to 76.90%， the awareness rate of nutrition labels increased from 53.59% to 69.06%， the rate of active reading of nutrition labels among diners increased from 73.38% to 81.23%， and the rate of selecting and purchasing food based on the information of nutrition labels increased from 69.27% to 77.79%， all of which were statistically significant （P<0.001）. ConclusionThe comprehensive interventions carried out through the creation of healthy canteens and restaurants have significantly impact on usage of oil， salt， and sugar， as well as on the nutritional knowledge and behaviors of diners.

Advances in neural circuits of innate fear defense behavior / 浙江大学学报·医学版

Fear, a negative emotion triggered by dangerous stimuli, can lead to psychiatric disorders such as phobias, anxiety disorders, and depression. Investigating the neural circuitry underlying congenital fear can offer insights into the pathophysiological mechanisms of related psychiatric conditions. Research on innate fear primarily centers on the response mechanisms to various sensory signals, including olfactory, visual and auditory stimuli. Different types of fear signal inputs are regulated by distinct neural circuits. The neural circuits of the main and accessory olfactory systems receive and process olfactory stimuli, mediating defensive responses like freezing. Escape behaviors elicited by visual stimuli are primarily regulated through the superior colliculus and hypothalamic projection circuits. Auditory stimuli-induced responses, including escape, are mainly mediated through auditory cortex projection circuits. In this article, we review the research progress on neural circuits of innate fear defensive behaviors in animals. We further discuss the different sensory systems, especially the projection circuits of olfactory, visual and auditory systems, to provide references for the mechanistic study of related mental disorders.

Application of continuous glucose monitoring technology to evaluate the advantages of insulin degludec in the treatment of type 1 diabetes mellitus / 中国医师杂志

Objective:Continuous glucose monitoring (CGM) technology is used to compare the advantages of insulin degludec (IDeg) as a basal insulin regimen compared with insulin glargine (IGlar) in the treatment of adult type 1 diabetes mellitus.Methods:30 adult patients with T1DM admitted to Heji Hospital Affiliated to Changzhi Medical College from September 2019 to December 2020 were screened. According to the random number table method, the patients were randomly divided into two groups (insulin degludec group and insulin glargine group) at a ratio of 1∶1, respectively treated with IDeg, IGlar and aspartate insulin for 12 weeks. The main outcome measures were the coefficient of variation of blood glucose (CV), mean amplitude of glycemic excursions (MAGE), time in range (TIR), time above range (TAR) and time below range (TBR). The secondary outcome measures were mean blood glucose (MBG), standard deviation of blood glucose (SD), fasting blood glucose (FPG), 2 h postprandial blood glucose (2 h BG), hemoglobin A1c (HbA 1c), means of daily differences (MOOD), and the frequency of hypoglycemic events. Results:At 12 weeks of treatment, the HbA 1c, FPG, 2 h BG, MBG, SD, CV and MAGE of insulin degludec group were lower than those of insulin glargine group, with statistically significant difference (all P<0.05). The TIR in the insulin degludec group was significantly higher than that in the insulin glargine group [73(63, 75)% vs 43(28, 63)%, P<0.001], and the TAR was lower than that in the glycerine group [25(17, 23)% vs 35(33, 64)%, P=0.003]. From the curve spectrum of blood glucose level of the two groups, the stability of blood glucose in the insulin degludec group was better than that in the insulin glargine group. After 12 weeks of treatment, 8 cases (8/15) in insulin degludec group had HbA 1c<7.0%, and 4 cases (4/15) in insulin glargine group had HbA 1c<7.0%, without statistically significant difference ( P=0.264). There were 7 cases (7/15) in the insulin degludec group and 1 case (1/15) in the insulin glargine group who achieved high quality blood glucose control, with statistically significant difference ( P=0.035). At the 12th week of outpatient follow-up, the incidence of nocturnal hypoglycemic events in insulin degludec group was significantly lower than that in insulin glargine group (4/15 vs 11/15, P=0.027). Conclusions:Compared with insulin glargine, insulin degludec can achieve higher blood glucose compliance rate, lower blood glucose level and reduce blood glucose fluctuations in patients with type 1 diabetes.

Prognostic Effect of Antibiotics on PD-1/PD-L1 Inhibitors in Treatment of Colorectal Cancer Patients / 胃肠病学

Background:Antibiotics can reduce the efficacy of immunotherapy for melanoma,non-small cell lung cancer and renal cell carcinoma by altering the intestinal microbiome,but their effect in the treatment of gastrointestinal cancer is unclear.Aims:To investigate the prognostic effect of antibiotics on PD-1/PD-L1 inhibitors in the treatment of colorectal cancer(CRC)patients.Methods:The clinicopathological data of 95 patients diagnosed with CRC and treated with immune checkpoint inhibitors(ICIs)from December 2018 to May 2022 at Renmin Hospital of Wuhan University were retrospectively analyzed,and the patients were divided into antibiotic group and control group according to whether antibiotics were used.Risk factors of progression free survival(PFS)and overall survival(OS)were analyzed by univariate and multivariate analysis.Results:Among the 95 patients with CRC,64 were male and 31 were female.The mean age was(60.46±11.82)years.PFS(10.9 months vs.24.8 months,P=0.032)and OS(14.5 months vs.35.5 months,P=0.008)were significantly decreased in antibiotic group than in control group,and one-year survival rate was 56.5%and 78.7%,respectively.Multivariate analysis showed that tumor location and antibiotic use were independent risk factors of PFS(P<0.05),while tumor location,antibiotic use and no radical surgery were independent risk factors of OS(P<0.05).Univariate and multivariate analyses showed that antibiotic administration route,dose were not risk factors of PFS(P>0.05);univariate analysis showed that antibiotic administration route was correlated with OS(P=0.045),however,multivariate analysis showed that antibiotic administration route,infection location were not risk factors of OS(P>0.05).Conclusions:Tumors located in colon and antibiotics applied within 30 days before and after the first dose of ICIs can shorten PFS and OS in CRC patients,while radical surgery can prolong the OS of CRC patients.

Retrospective analysis of the effect of oral nutritional supplements during labor on delivery outcomes in low-risk pregnant women / 中华临床营养杂志

Objective:To explore the effect of oral nutritional supplements (ONS) during labor on delivery outcomes in low-risk pregnant women and the risk factors of cesarean section.Methods:A retrospective analysis was conducted in a total of 206 full-term pregnant women with singleton and cephalic presentation at the delivery center in our hospital from March 15th to May 15th, 2022. Standard diet education was given to all those women by midwives. Pregnant women who received the enteral nutrient solution prepared by the Department of Clinical Nutrition during labor were in the ONS group ( n = 110), while those who did not were in the control group ( n = 96). The baseline characteristics and delivery outcomes were compared between the two groups, and the risk factors of cesarean section were also analyzed. Results:There were no significant differences in terms of maternal age, height, baseline weight, baseline body mass index (BMI), weight gain during pregnancy, prenatal BMI, gestational week, intraspinal labor analgesia, oxytocin, gastrointestinal intolerance, neonatal length, and weight between the two groups ( P > 0.05). However, the total oral energy intake during labor in the ONS group was significantly higher than that in the control group ([1 349.99± 569.51] kJ vs [249.59 ± 455.19] kJ, P < 0.01). The rate of vaginal delivery in the ONS group was significantly higher than that in the control group (93.6% vs 81.3%, P = 0.01), and the duration of the first stage of labor ([487.06 ± 232.94] min vs [416.17 ± 191.13] min, P = 0.03) was also significantly longer in the ONS group. There were no significant differences between the two groups in terms of the duration of the second and third stages of labor, perineal laceration, cervical laceration, vaginal laceration, amount of bleeding, hospital stay, and Apgar score after birth ( P > 0.05). Multivariate logistic regression analysis showed that maternal age was a risk factor for changing to cesarean section in women with low-risk pregnancies ( OR 1.20, 95% CI 1.03 to 1.40, P = 0.02), while ONS during labor ( OR 0.31, 95% CI 0.11 to 0.85, P = 0.02) and intraspinal labor analgesia ( OR 0.10, 95% CI 0.04 to 0.26, P < 0.01) were protective factors. Conclusions:ONS during labor can significantly increase the vaginal delivery rate, without increasing the incidence of gastrointestinal intolerance in low-risk pregnant women. Maternal age is a risk factor for cesarean section while ONS during labor and intraspinal labor analgesia are protective factors in women with low-risk pregnancies.

Effect of calorie-restricted diet combined with intestinal microecological preparation on clinical outcomes in overweight/obese infertile patients / 中华临床营养杂志

Objective:To investigate the effects of calorie-restricted diet (CRD) combined with intestinal microecological preparation on the clinical outcomes in overweight/obese infertile patients undergoing frozen-thawed embryo transfer (FET) cycle.Methods:252 overweight/obese infertile patients who met the inclusion and exclusion criteria were included and divided into overweight intervention group, overweight control group, obese intervention group and obese control group, according to body mass index (BMI) and whether or not they received nutritional intervention. Clinical outcome indexes and changes in anthropometry and body composition before and after intervention were compared across all groups.Results:Body mass, BMI, body fat percentage, waist-to-hip ratio and visceral fat grade were significantly decreased after nutritional intervention in both overweight and obese intervention groups (both P<0.001). Among overweight patients, follicle count [(17.89±4.97) vs. (16.22±5.41), P=0.027], live births [(0.64±4.77) vs. (0.36±8.61), P=0.005] and the rate of live birth (47.19% vs. 30.19%, P=0.005) were significantly increased in the intervention group compared with the control group. Among obese patients, live births [(0.89±3.79) vs. (0.48±3.69), P=0.040] and the rate of live birth (64.29% vs. 37.93%, P=0.047) were significantly increased in the intervention group. Conclusion:In overweight and obese infertile patients undergoing FET cycle, the nutritional intervention of CRD combined with complex intestinal microecological preparation can help reduce weight and body fat, and may be beneficial to improving the success rate of assisted reproductive technology.

Nutrient content of 122 kinds of retail handcrafted milk tea products in Shanghai / 环境与职业医学

Background The retail milk tea industry is in a period of rapid development, but there is little research on its nutrient content, which restricts the nutritional guidance of milk tea. Objective To determine the levels of nutrients in best-selling handcrafted milk tea in Shanghai and analyze the nutritional characteristics. Methods In 2018 and 2021, a total of 13 handcrafted milk tea brands with ≥3 branch stores in Shanghai were selected by searching for milk tea on Meituan and Ele.me food delivery platforms, and a total of 122 types of handcrafted milk tea products were collected from the top three sales [milk tea (including all sweetness levels available), milk cover tea, and fruit tea]. National standard methods were used to detect energy, protein, fat, carbohydrate, sugar, trans fatty acid, calcium, caffeine, and tea polyphenol. Results The median energy of the milk tea samples was 310 kJ (per 100 g sample). The main sources of energy were carbohydrate and fat. The levels of energy, protein, and fat in milk cover tea and milk tea were significantly higher than those in fruit tea (P＜0.05), and there was no significant difference in carbohydrate among them. The total sugar, fructose, and glucose levels in milk tea were significantly lower than those in milk cover tea and fruit tea, and the lactose level in fruit tea was significantly lower than those in milk tea and milk cover tea (P＜0.05). Themedian trans fat acid level in milk cover tea was higher than that in milk tea (P＜0.05). The median levels of caffeine and tea polyphenol were higher in milk tea than in milk cover tea (P＜0.05). The levels of energy, carbohydrate, sucrose, total sugar, and calcium in milk tea were positively correlated with the number of ingredients added (0-3) (r=0.386, 0.371, 0.238, 0.698, 0.466, respectively, P < 0.05). The levels of energy, carbohydrate, and total sugar tended to increase with increasing sweetness (P<0.05), and total sugar was mainly sucrose, followed by fructose and glucose. The total sugar levels of the samples labeled sugar free, light sugar, half sugar, less sugar, and regular sugar were 3.40 (2.20, 4.9), 4.97 (4.25, 5.97), 5.80 (4.31, 6.88), 6.59 (5.17, 8.53), and 7.96 (6.82, 9.20) g, respectively; the proportions of the samples containing more than 0.5 g of total sugar were 93.3% for sugar free milk tea, 47.4% for light sugar milk tea, and 94.0% for regular sugar milk tea; the proportion of the regular sugar samples with sugar content greater than 10 g was 18.0% (all samples with nominal sugar content were measured per 100 g). Conclusion The retail handcrafted milk tea in Shanghai is characterized by high energy, high added sugar, high fat, and low protein. It is necessary to standardize the added sugar content and sweetness labeling, strengthen the nutrition education of milk tea, and guide residents to limit its intake.

Associations of sugar-sweetened beverages intake frequency with physical growth and glucolipid metabolism among children and adolescents / 环境与职业医学

Background Children and adolescents drink sugar-sweetened beverages (SSBs) frequently. Research has confirmed that SSBs associate with weight gain and overweight or obesity. However, it is unclear whether high SSBs intake associates with abnormal changes in physical growth and glucolipid metabolism before causing adverse health outcomes such as overweight and obesity. Early identification of associated health risks of overconsumption of SSBs have important public health implications. Objective To investigate the differences in physical growth and glucolipid metabolism between different SSBs intake frequency groups in normal weight children and adolescents aged 6-17 years, and to evaluate the early effects of SSBs intake on physical growth and glycolipid metabolism before causing overweight and obesity, aiming to provide a scientific basis for the prevention and control of childhood overweight and obesity and related chronic diseases, and for the formulation of policies on the control of SSBs consumption. Methods Data were from the Shanghai Diet and Health Survey (SDHS) among primary and secondary school students. The participants were normal weight children and adolescents aged 6-17 years. Propensity scores were calculated according to energy intake and physical activity factors, after stratifying by age and gender. Participants were 1:1 matched with the closest propensity scores in the high-frequency (≥1 time·d−1) and the low-frequency (≤1 time·week−1) SSBs intake groups. The outcome indicators were physical measurements such as height, weight, percent of body fat, and waist circumference, and metabolic indicators such as fasting blood glucose, total triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Body mass index (BMI) was calculated. Food frequency questionnaire was used to collect SSBs consumption in the past three months through face-to-face interview. A paired t-test was used to compare the differences in physical and glycolipid metabolic indicators between the high-frequency intake group and the low-frequency intake group of SSBs. Results A total of 431 pairs were obtained. For children and adolescents in grades 6-9, overall height (difference=2.92 cm, P=0.002), weight (difference=2.53 kg, P=0.003), and waist circumference (difference=1.34 cm, P=0.035) were higher in those who consumed SSBs ≥1 time·d−1 than in those who consumed ≤1 time·week−1. For children and adolescents in grades 10-12, overall weight (difference=2.27 kg, P=0.041) was higher in those who consumed SSBs ≥1 time·d−1 than in those who consumed ≤1 time·week−1. Over 95% of the study subjects reported blood glucose and lipid test results within the normal range; but girls in grades 1-5 who consumed SSBs ≥1 time·d−1 had a higher total cholesterol (difference=0.20 mmol·L−1, P=0.027) and low-density lipoprotein cholesterol (difference=0.19 mmol·L−1, P=0.010) than those who consumed ≤1 time·week−1; boys in grades 6-9 who consumed SSBs ≥1 time·d−1 had a lower high-density lipoprotein cholesterol (difference=-0.10 mmol·L−1, P=0.039) than those who consumed ≤1 time·week−1. Conclusion High-frequency intake of SSBs may be associated with higher total cholesterol and low-density lipoprotein cholesterol in normal weight children and adolescents in grades 1-5, and higher weight in normal weight children and adolescents in grades 6-12. There is an urgent need to educate children and adolescents about nutritional health, enhance their ability to make healthy food and beverage choices, and take early interventions to control the intake of SSBs in children.

Development of a method for determination of osmotic pump controlled-release tablets of lorcaserin hydrochloride in beagle dog plasma and its application to pharmacokinetic study / 中国药理学通报

Aim To develop an UPLC-MS/MS method to determine the concentration of lorcaserin hydrochloride in beagle plasma, and study the pharmacokinetics of osmotic pump controlled-release tablets of lorcaserin hydrochloride. Methods A randomized crossover design was used, carbamazepine as the internal standard(IS), and plasma protein precipitation with acetonitrile. The chromatographic was Phenomenex Polar C18 column(100 mm×2. 1 mm, 3 μm), and acetonitrile - water(containing 10 mmol·L-1 ammonium acetate and 0.1% formic acid)(40:60, V/V)was mobile phase. Multiple reaction monitoring mode and electrospray positive ionization were used to detect lorcaserin hydrochloride. The MS/MS ion transitions were monitored at m/z 196.2→129.2 for lorcaserin hydrochloride and m/z 237→194.1 for carbamazepine, respectively. Results The linear range was 1 to 500 μg·L-1(r=0.999 2), the extraction recovery rate ranged from 87.70% to 89.70%, the precision RSD was 9.7%. The accuracy and matrix effect met the requirements, and the stability of lorcaserin hydrochloride was good in -20 ℃ refrigerator for 45 d, repeated freezing and thawing for three times, placed at room temperature for 24 h, and the disposed samples placed in automatsampler for 6 h were stable. The main pharmacokinetic parameters of the controlled-release tablet and immediate-release tablet were as follows:Tmax was(8.00±1.27)h and(1.00±0.13)h, Cmax was(70.56±3.73)μg·L-1 and(176.33±16.73)μg·L-1, and AUC0-t was(966.33±7.56)μg·h·L-1 and(973.05±69.09)μg·h·L-1, respectively. Conclusions The established UPLC-MS/MS method can be used to study the pharmacokinetics of lorcaserin hydrochloride in the plasma of beagle dogs, and osmotic pump controlled-release tablets has sustained release effect.

Construction of hiPSC-derived Excitatory Neural Network-like Tissue / 中山大学学报(医学科学版)

ObjectiveTo construct a neural network-like tissue with the potential of synaptic formation in vitro by seeding human induced pluripotent stem cell-derived neural precursor cells （hiPSC-NPCs） on decellularized optic nerve （DON）， so as to provide a promising approach for repair of nerve tissue injury. MethodsThrough directional induction and tissue engineering technology， human induced pluripotent stem cells （hiPSCs） and 3D DON scaffolds were combined to construct neural network-like tissues. Then the hiPSCs were directionally induced into human neural precursor cells （hNPCs） and neurons. Immunofluorescence staining was used to identify cell differentiation efficiency. 3D DON scaffolds were prepared. Morphology and cytocompatibility of scaffolds were identified by scanning electron microscopy and Tunnel staining. Induced hiPSC-NPCs were seeded on DON scaffolds. Immunofluorescence staining， scanning electron microscopy， transmission electron microscopy and patch clamp were used to observe the morphology and functional identification of constructed neural network tissues. Results①The results of immunofluorescence staining suggested that most of hiPSC-NPCs differentiated into neurons in vitro. We had successfully constructed a neural network dominated by neurons. ② The results of scanning electron microscopy and immunohistochemistry suggested that a neural network-like tissue with predominating excitatory neurons in vitro was successfully constructed. ③The results of immunohistochemical staining， transmission electron microscopy and patch clamp indicated that the neural network-like tissue had synaptic transmission function. ConclusionA neural network-like tissue mainly composed of excitatory neurons has been constructed by the combination of natural uniform-channel DON scaffold and hiPSC-NPCs， which has the function of synaptic transmission. This neural network plays a significant role in stem cell derived replacement therapy， and offers a promising prospect for repair of spinal cord injury （SCI） and other neural tissue injuries.