Reconstruction of a fatty acid synthesis cycle from acyl carrier protein and cofactor structural snapshots.

Fatty acids (FAs) play a central metabolic role in living cells as constituents of membranes, cellular energy reserves, and second messenger precursors. A 2.6 MDa FA synthase (FAS), where the enzymatic reactions and structures are known, is responsible for FA biosynthesis in yeast. Essential in the yeast FAS catalytic cycle is the acyl carrier protein (ACP) that actively shuttles substrates, biosynthetic intermediates, and products from one active site to another. We resolve the S. cerevisiae FAS structure at 1.9 Å, elucidating cofactors and water networks involved in their recognition. Structural snapshots of ACP domains bound to various enzymatic domains allow the reconstruction of a full yeast FA biosynthesis cycle. The structural information suggests that each FAS functional unit could accommodate exogenous proteins to incorporate various enzymatic activities, and we show proof-of-concept experiments where ectopic proteins are used to modulate FAS product profiles.

Atomic-resolution protein structure determination by cryo-EM.

Single-particle electron cryo-microscopy (cryo-EM) is a powerful method for solving the three-dimensional structures of biological macromolecules. The technological development of transmission electron microscopes, detectors and automated procedures in combination with user-friendly image processing software and ever-increasing computational power have made cryo-EM a successful and expanding technology over the past decade1. At resolutions better than 4 Å, atomic model building starts to become possible, but the direct visualization of true atomic positions in protein structure determination requires much higher (better than 1.5 Å) resolution, which so far has not been attained by cryo-EM. The direct visualization of atom positions is essential for understanding the mechanisms of protein-catalysed chemical reactions, and for studying how drugs bind to and interfere with the function of proteins2. Here we report a 1.25 Å-resolution structure of apoferritin obtained by cryo-EM with a newly developed electron microscope that provides, to our knowledge, unprecedented structural detail. Our apoferritin structure has almost twice the 3D information content of the current world record reconstruction (at 1.54 Å resolution3). We can visualize individual atoms in a protein, see density for hydrogen atoms and image single-atom chemical modifications. Beyond the nominal improvement in resolution, we also achieve a substantial improvement in the quality of the cryo-EM density map, which is highly relevant for using cryo-EM in structure-based drug design.

Physical Fitness and Body Mass Index Status of Hong Kong Primary Schoolchildren across the COVID-19 Pandemic, before and after School Closure.

OBJECTIVE: To determine whether health-related physical fitness and body mass index (BMI) status differed before and after school closure from the COVID-19 pandemic in a population-based cohort of Hong Kong primary schoolchildren. STUDY DESIGN: We examined the BMI z score, BMI status, and physical fitness z scores including (i) upper limb muscle strength, (ii) 1-minute sit-up test, (iii) sit-and-reach test, and (iv) endurance run tests, among 3 epochs: prepandemic (September 2018-August 2019), before school closure (September 2019-January 2020), and partial school reopening (September 2021-August 2022), using a repeated cross-sectional approach. RESULTS: A total of 137 752 primary schoolchildren aged 6-12 years were recruited over 3 academic years. Obesity increased significantly from 25.9% in 2018/19 to 31.0% in 2021/22, while underweight increased slightly from 6.1% to 6.5%. All tested parameters were adversely affected by the pandemic. The negative trend over time was far more pronounced in all 4 physical fitness scores in the underweight group, although performance in handgrip strength had no significance between 2018/19 and 2021/22. CONCLUSIONS: Schoolchildren who are both underweight and overweight/obese are vulnerable to adverse changes in physical fitness during the COVID-19 pandemic. To eliminate the negative health and fitness outcomes, it is urgent to develop strategies for assisting schoolchildren in achieving a healthy weight, especially in the postpandemic era.

A fluorescent probe for STED microscopy to study NIP-specific B cells.

We have developed a series of monovalent fluorophore-conjugated affinity probes based on the hapten 3-nitro-4-hydroxy-5-iodophenylacetyl (NIP), which is widely used as a model antigen to study B lymphocytes and the functional principles of B cell antigen receptors (BCRs). We successfully used them in flow-cytometry, confocal and super-resolution microscopy techniques.

Prediction of spontaneous preterm birth by cervical length in the first trimester of pregnancy: Comparison of two measurement methods.

INTRODUCTION: Our objectives were to compare the single-line and two-line methods of cervical length measurement in the first trimester of pregnancy and to evaluate the potential value of the first trimester cervical length measured by the two methods in predicting spontaneous preterm birth. MATERIAL AND METHODS: This was a prospective study in singleton pregnancies at 11+0 to 13+6  weeks of gestation. Cervical length was measured by two methods: (i) a linear distance between the two ends of the glandular area around the endocervical canal (single-line method) and (ii) a sum of a linear distance from the internal os to the greatest cervical curvature and a linear distance from this point of the cervix to the external os (two-line method). The screening performance of the first trimester cervical length measured by the two different methods for the prediction of spontaneous preterm delivery was assessed by receiver-operating characteristics (ROC) curve analysis. The areas under the ROC (AUROC) were compared by De Long test. RESULTS: A total of 1484 consecutive singleton pregnancies were included in this study. Spontaneous preterm delivery at <37 and <32 weeks occurred in 75 cases (5.1%) and 12 cases (0.8%), respectively. The median cervical length measured by the single-line method was significantly shorter than that by the two-line method (33.5 vs 36.5 mm, p < .001). Compared with the term delivery group, the median cervical length measured by the two-line method was shorter in women with spontaneous delivery at <32 weeks of gestation (36.5 vs 33.6 mm, p < .01). No significant difference in the median cervical length measured by the single-line method was detected between the spontaneous preterm delivery and term delivery groups. Receiver-operating-characteristic curves demonstrated that cervical length measured by the two-line method achieved better performance in predicting spontaneous delivery at <32 weeks compared with the single-line method (AUROC: 0.72 vs 0.61, p < .01). CONCLUSIONS: We have demonstrated that the first trimester cervical length, measured by the two-line approach, holds promise as a potential screening tool for early spontaneous preterm delivery.

Ultrasound-Assisted Extraction May Not Be a Better Alternative Approach than Conventional Boiling for Extracting Polysaccharides from Herbal Medicines.

In clinical practice polysaccharides from herbal medicines are conventionally prepared by boiling water extraction (BWE), while ultrasound-assisted extraction (UAE) has often been used instead employed in laboratory research due to its strong extraction ability and efficiency. However, if and how the polysaccharides obtained by UAE and BWE are comparable, and hence whether the UAE-based research is instructive for the actual usage of herbal polysaccharides still requires further evaluation. To address this issue, here we chemically analyzed and compared the UAE- and BWE-obtained polysaccharides from three herbal medicines, i.e., Ginseng Radix, Astragali Radix and Dendrobii Officinalis Caulis. Then, the spike recovery of two series of standard dextran and pullulan by UAE and BWE was tested. The results showed that the polysaccharides from the herbal medicines by UAE were quantitatively and qualitatively different with those by BWE. The powerful extraction ability and polysaccharide degradation caused by ultrasound collectively contributed to these differences. It was then revealed that not only the UAE conditions but also the polysaccharide structures could affect the extraction ability and polysaccharide degradation. Given these, we highly recommended that the effects of UAE on polysaccharides from herbal medicines should be first carefully considered before employing it in relevant chemical and pharmacological analysis.

Normative values of motor performance and their relationship with BMI status in Hong Kong preschoolers.

This study aimed to establish sex- and age-specific reference values for motor performance (MP) in Hong Kong preschoolers aged 3-5 years old and examine the relationship between MP and BMI status. A cross-sectional study was conducted among 5579 preschoolers in Hong Kong. Three MP tests were administered, and height and weight information were collected. GAMLSS was used to compute the normative values of the motor tests. Boys outperformed girls in activities requiring muscle strength and power, while girls outperformed boys in activities requiring balance and coordination. The MP scores increased with age for both overarm beanbag throw and standing long jump for both sexes, while the one-leg balance scores showed larger differences between P50 and P95 in older preschoolers. Children with excessive weight performed worse in standing long jump and one-leg balance compared to their healthy weight peers. This study provides valuable information on the MP of preschoolers in Hong Kong, including sex- and age-specific reference values and the association between BMI status and MP scores. These findings can serve as a reference for future studies and clinical practice and highlight the importance of promoting motor skill development in preschoolers, particularly those who are overweight or obese.

Effectiveness of BNT162b2 and CoronaVac in children and adolescents against SARS-CoV-2 infection during Omicron BA.2 wave in Hong Kong.

BACKGROUND: The SARS-CoV-2 Omicron BA.2 subvariant replaced BA.1 globally in early 2022, and caused an unprecedented tsunami of cases in Hong Kong, resulting in the collapse of elimination strategy. Vaccine effectiveness (VE) of BNT162b2 and CoronaVac against BA.2 is unclear. METHODS: We utilize an ecological design incorporating population-level vaccine coverage statistics and territory-wide case-level SARS-CoV-2 infection surveillance data, and investigate the VE against infection during the Omicron BA.2 wave between January 1 to April 19, 2022, in Hong Kong for children and adolescents. RESULTS: We estimate VE to be 33.0% for 1 dose of BNT162b2 in children aged 5-11 and 40.8% for 2 doses of CoronaVac in children aged 3-11. We also estimate 54.9% VE for 2 doses of BNT162b2, and 55.0% VE for 2 doses of CoronaVac in adolescents aged 12-18. CONCLUSIONS: Our findings support partly preserved VE against infection by variants of concerns for children and adolescents in settings with extremely low levels of prior SARS-CoV-2 circulation.

COVID-19 vaccines BNT162b2 and CoronaVac are widely used globally in children and adolescents, yet their effectiveness against Omicron BA.2 variant­a version of the SARS-CoV-2 virus that became predominant in early 2022­is not fully known. In Hong Kong, we combine population-level vaccine coverage statistics and territory-wide SARS-CoV-2 infection data, and estimate their effectiveness against SARS-CoV-2 infection in children and adolescents during a major Omicron BA.2 outbreak. We find moderate vaccine effectiveness after 2 doses of BNT162b2 or CoronaVac, supporting the use of either vaccine in children and adolescents during a rapidly evolving pandemic.

COVID-19 vaccines versus pediatric hospitalization.

Vaccine effectiveness of BNT162b2 and CoronaVac against COVID-19-associated hospitalization and moderate-to-severe disease due to SARS-CoV-2 Omicron BA.2 is studied from the 1.36 million doses administered to 766,601 of 953,400 children aged 3-11 years and adolescents aged 12-18 years in Hong Kong as of April 2022. These vaccines confer substantial protection.

Identifying the High-Risk Population for COVID-19 Transmission in Hong Kong Leveraging Explainable Machine Learning.

The worldwide spread of COVID-19 has caused significant damage to people's health and economics. Many works have leveraged machine learning models to facilitate the control and treatment of COVID-19. However, most of them focus on clinical medicine and few on understanding the spatial dynamics of the high-risk population for transmission of COVID-19 in real-world settings. This study aims to investigate the association between population features and COVID-19 transmission risk in Hong Kong, which can help guide the allocation of medical resources and the implementation of preventative measures to control the spread of the pandemic. First, we built machine learning models to predict the number of COVID-19 cases based on the population features of different tertiary planning units (TPUs). Then, we analyzed the distribution of cases and the prediction results to find specific characteristics of TPUs leading to large-scale outbreaks of COVID-19. We further evaluated the importance and influence of various population features on the prediction results using SHAP values to identify indicators for high-risk populations for COVID-19 transmission. The evaluation of COVID-19 cases and the TPU dataset in Hong Kong shows the effectiveness of the proposed methods. The top three most important indicators are identified as people in accommodation and food services, low income, and high population density.

A mixed-methods study on the association of six-month predominant breastfeeding with socioecological factors and COVID-19 among experienced breastfeeding women in Hong Kong.

BACKGROUND: In the past decade, various breastfeeding policies were implemented in Hong Kong, including changes in perinatal guidelines in public hospitals, adoption of the Baby-Friendly Hospital Initiative (BFHI), provision of guidelines for the marketing of formula milk, penalisation of discrimination towards breastfeeding, and extension of the statutory maternity leave. Meanwhile, the COVID-19 pandemic brought new challenges and opportunities to breastfeeding practices. Infection control measures in public hospitals included the cancellation of antenatal classes, hospital tours, and postnatal classes; suspension of perinatal visiting periods; and compulsory separation of COVID-19 positive mothers from newborns. In addition, work-from-home policies were widely implemented. This study aimed to identify the associated factors of six-month predominant breastfeeding (PBF), and to evaluate the impact of COVID-19 on breastfeeding practice. METHODS: This study was conducted from 1 March 2021 to 7 April 2021 using a mixed-methods approach. An electronic questionnaire was distributed to members of breastfeeding or parenting groups who have had breastfeeding experience in the past 10 yrs. Logistic and linear regression analyses were conducted to identify factors associated with six-month PBF both in general and during the pandemic period. A qualitative content analysis was conducted using an inductive approach. RESULTS: The study included 793 participants. Giving birth in a public hospital (OR 2.21; 95% CI 1.46, 3.34) and breastfeeding support from family and friends (OR 1.28; 95% CI 1.05, 1.57) were significantly associated with six-month PBF, even during COVID-19. Factors associated with the self-rated impact of COVID-19 on breastfeeding include working from home, the perceived immunological benefits of breastfeeding, and the wish to avoid breastfeeding or expressing breast milk in public premises. Furthermore, breastfeeding practice in public hospitals was more likely to be affected by the busyness of staff, while private hospitals had worse rooming-in practices and staff who had inadequate breastfeeding knowledge. CONCLUSIONS: Giving birth in a public hospital and having breastfeeding support from family and friends were associated with six-month PBF. Furthermore, COVID-19 in Hong Kong had an overall positive impact on six-month PBF. Further studies should investigate the impact of hospital practices and the COVID-19 pandemic on breastfeeding behaviours.

An anti-inflammatory and anti-fibrotic proprietary Chinese medicine nasal spray designated as Allergic Rhinitis Nose Drops (ARND) with potential to prevent SARS-CoV-2 coronavirus infection by targeting RBD (Delta)- angiotensin converting enzyme 2 (ACE2) binding.

BACKGROUND: Since the outbreak of COVID-19 has resulted in over 313,000,000 confirmed cases of infection and over 5,500,000 deaths, substantial research work has been conducted to discover agents/ vaccines against COVID-19. Undesired adverse effects were observed in clinical practice and common vaccines do not protect the nasal tissue. An increasing volume of direct evidence based on clinical studies of traditional Chinese medicines (TCM) in the treatment of COVID-19 has been reported. However, the safe anti-inflammatory and anti-fibrotic proprietary Chinese medicines nasal spray, designated as Allergic Rhinitis Nose Drops (ARND), and its potential of re-purposing for suppressing viral infection via SARS-CoV-2 RBD (Delta)- angiotensin converting enzyme 2 (ACE2) binding have not been elucidated. PURPOSE: To characterize ARND as a potential SARS-CoV-2 entry inhibitor for its possible preventive application in anti-virus hygienic agent. METHODS: Network pharmacology analysis of ARND was adopted to asacertain gene targets which were commonly affected by COVID-19. The inhibitory effect of ARND on viral infection was determined by an in vitro pseudovirus assay. Furthermore, ARND was confirmed to have a strong binding affinity with ACE2 and SARS-CoV-2 spike-RBD (Delta) by ELISA. Finally, inflammatory and fibrotic cell models were used in conjunction in this study. RESULTS: The results suggested ARND not only inhibited pseudovirus infection and undermined the binding affinity between ACE2 and the Spike protein (Delta), but also attenuated the inflammatory response upon infection and may lead to a better prognosis with a lower risk of pulmonary fibrosis. The data in this study also provide a basis for further development of ARND as an antiviral hygienic product and further investigations on ARND in the live virus, in vivo and COVID-19 patients. ARND holds promise for use in the current COVID-19 outbreak as well as in future pandemics. CONCLUSION: ARND could be considered as a safe anti-SARS-CoV-2 agent with potential to prevent SARS-CoV-2 coronavirus infection.

Age- and Sex-Specific Physical Fitness Reference and Association with Body Mass Index in Hong Kong Chinese Schoolchildren.

There is lacking a population-based study on the fitness level of Hong Kong schoolchildren, and it seems that increasing childhood obesity prevalence has shifted the classification of healthy fitness, with 'underfit' as normal. This cross-sectional territory study aimed to develop an age- and sex-specific physical fitness reference using a representative sample of children aged 6-17 and to determine the associations with body mass index in schoolchildren. The study analyzed Hong Kong School Physical Fitness Award Scheme data covering grade 1 to grade 12 students' physical fitness and anthropometric measurements from 2017 to 2018. This reference was established without the impact due to COVID-19. Four aspects of physical fitness tests were measured using a standardized protocol, including (i) upper limb muscle strength, (ii) one-minute sit-up, (iii) sit-and-reach, and (iv) endurance run tests. The generalized additive model for location, scale, and shape was used to construct the reference charts. A Mann-Whitney U test was used to compare the mean differences in age, weight, and height, and a Pearson's chi-square test was used to examine the distributions of sex groups. A Kruskal-Wallis test was used to compare the group differences in BMI status, followed by the Dunn test for pairwise comparisons. A 5% level of significance was regarded as statistically significant. Data of 119,693 students before the COVID-19 pandemic were included in the analysis. The association between physical fitness level and BMI status varied depending on the test used, and there were significant differences in fitness test scores among BMI groups. The mean test scores of the obese group were lower in most of the tests for both boys and girls, except for handgrip strength. The underweight group outperformed the obese group in push-ups, one-minute sit-ups, and endurance run tests, but not in handgrip strength. In conclusion, a sex- and age-specific physical fitness reference value for Hong Kong Chinese children aged 6 to 17 years old is established, and this study demonstrated a nonlinear relationship between BMI status and physical fitness. The reference will help to identify children with poor physical fitness to offer support and guidance on exercise training. It also serves as a baseline for assessing the impact of the COVID-19 pandemic on Hong Kong students' physical fitness.

Impact of COVID-19 Pandemic on School-Aged Children's Physical Activity, Screen Time, and Sleep in Hong Kong: A Cross-Sectional Repeated Measures Study.

Despite concerns about the negative effects of social distancing and prolonged school closures on children's lifestyle and physical activity (PA) during the COVID-19 pandemic, robust evidence is lacking on the impact of the pandemic-related school closures and social distancing on children's wellbeing and daily life. This study aimed to examine changes in the PA levels, sleep patterns, and screen time of school-aged children during the different phases of the COVID-19 outbreak in Hong Kong using a repeated cross-sectional design. School students (grades 1 to 12) were asked to report their daily electronic device usage and to fill in a sleep diary, recording their daily sleep onset and wake-up time. They were equipped with a PA monitor, Actigraph wGT3X-BT, to obtain objective data on their PA levels and sleep patterns. Students were recruited before the pandemic (September 2019-January 2020; n = 577), during school closures (March 2020-April 2020; n = 146), and after schools partially reopened (October 2020-July 2021; n = 227). Our results indicated lower PA levels, longer sleep duration, and longer screen time among participants recruited during school closures than those recruited before the COVID-19 outbreak. Primary school students were found to sleep on average for an extra hour during school closures. The later sleep onset and increased screen time documented during school closures persisted when schools partially reopened. Our findings illustrate the significant impact of social distancing policies during the COVID-19 pandemic on the sleep pattern, screen time, and PA level in school-aged children in Hong Kong. Professionals should urgently reinforce the importance of improving physically activity, good sleep hygiene, and regulated use of electronic devices for parents and school-aged children during this unprecedented time.

A hybrid platform featuring nanomagnetic ligand fishing for discovering COX-2 selective inhibitors from aerial part of Saussurea laniceps Hand.-Mazz.

ETHNOPHARMACOLOGICAL RELEVANCE: Saussurea laniceps Hand.-Mazz. (Compositae) is a representative "snow lotus" herb well known in Chinese folk medicine to treat inflammation-related diseases such as arthritis. S. laniceps (SL) shows anti-inflammatory and analgesic potencies and contains various constituents potentially with cyclooxygenase-2 (COX-2) selective inhibition. The herb is a valuable source of natural alternatives to synthetic COX-2 selective nonsteroidal anti-inflammatory drugs, a common medication for rheumatoid arthritis (RA) and osteoarthritis (OA) reported with serious cardiovascular side effects. AIM OF THE STUDY: Based on an innovative drug screening platform, this study aimed to discover safe, effective COX-2 selective inhibitors from SL. MATERIALS AND METHODS: An enzyme-anchored nanomagnetic fishing assay was developed to separate COX-2 ligands from SL. Cell and animal models of cardiomyocytes, lipopolysaccharide-stimulated macrophages, rat adjuvant-induced arthritis, and anterior cruciate ligament transection-induced OA rats, were adopted to screen the single/combined ligands regarding toxicity and bioactivity levels. Molecular docking was employed to unravel binding mechanisms of the ligands towards COX-1 and COX-2. RESULTS: Four COX-2 selective compounds were separated from SL using optimized COX-2-functionalized magnetic nanoparticles. All the four ligands were proved with evidently lower cardiotoxicity both in vitro and in vivo than celecoxib, a known COX-2 selective inhibitor. Two ligands, scopoletin and syringin, exhibited potent anti-arthritic activities in rat models of RA and OA by alleviating clinical statuses, immune responses, and joint pathological features; their optimum combination ratio was discovered with stronger remedial effects on rat OA than single administrations. The COX-1/2 binding modes of the two phytochemicals contributed to explain their cardiac safety and therapeutic performances. CONCLUSIONS: The screened chemicals are promising to be developed as COX-2 selective inhibitors as part of treating RA and OA. The hybrid strategy for discovering therapeutic agents from SL is shown here to be efficient; it should be equally valuable for finding other active chemicals in other natural sources.

Ginseng ameliorates exercise-induced fatigue potentially by regulating the gut microbiota.

The therapeutic effects of water extract of ginseng (WEG) on exercise-induced fatigue (EF) have been reported in several previous studies, but the molecular mechanisms involved remain unexplored. In this study, the anti-EF effects of WEG were studied, and the potential mechanisms were discussed. We characterized the chemical components of WEG by ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS) and high performance liquid chromatography coupled with evaporative light scattering detection (HPLC-ELSD), and then examined the anti-EF effects of WEG on a rat model of weight-loaded swimming with a focus on endogenous metabolism and gut microbiota. WEG contains abundant (90.15%, w/w) saccharides and ginsenosides with structurally diverse glycosyls. WEG taken orally showed strong anti-EF effects by ameliorating energy metabolism abnormality, oxidative stress, lipid peroxidation, inflammatory response, disorders in the metabolism of bile acid, amino acid, fatty acid and lipid, as well as the gut microbiota dysbiosis. Given that gut microbiota is significantly associated with energy expenditure, systemic inflammation and host metabolism, these findings suggest a potential central role of the gut microbiota in mediating the anti-EF effect of WEG. That is, the saccharides and ginsenosides in WEG serve as energy substrates for specific intestinal bacteria, thereby beneficially regulating the gut microbiota, and the reshaped gut microbial ecosystem then triggers several molecular and cellular signaling pathways (e.g. butyrate or TGR5 signals) to achieve the therapeutic effects on EF. The outcomes highlighted here enable deeper insight into how WEG overcomes EF.

Synergistic effects of autophagy/mitophagy inhibitors and magnolol promote apoptosis and antitumor efficacy.

Mitochondria as a signaling platform play crucial roles in deciding cell fate. Many classic anticancer agents are known to trigger cell death through induction of mitochondrial damage. Mitophagy, one selective autophagy, is the key mitochondrial quality control that effectively removes damaged mitochondria. However, the precise roles of mitophagy in tumorigenesis and anticancer agent treatment remain largely unclear. Here, we examined the functional implication of mitophagy in the anticancer properties of magnolol, a natural product isolated from herbal Magnolia officinalis. First, we found that magnolol induces mitochondrial depolarization, causes excessive mitochondrial fragmentation, and increases mitochondrial reactive oxygen species (mtROS). Second, magnolol induces PTEN-induced putative kinase protein 1 (PINK1)‒Parkin-mediated mitophagy through regulating two positive feedforward amplification loops. Third, magnolol triggers cancer cell death and inhibits neuroblastoma tumor growth via the intrinsic apoptosis pathway. Moreover, magnolol prolongs the survival time of tumor-bearing mice. Finally, inhibition of mitophagy by PINK1/Parkin knockdown or using inhibitors targeting different autophagy/mitophagy stages significantly promotes magnolol-induced cell death and enhances magnolol's anticancer efficacy, both in vitro and in vivo. Altogether, our study demonstrates that magnolol can induce autophagy/mitophagy and apoptosis, whereas blockage of autophagy/mitophagy remarkably enhances the anticancer efficacy of magnolol, suggesting that targeting mitophagy may be a promising strategy to overcome chemoresistance and improve anticancer therapy.

Brain Microstructural Changes Associated With Neurocognitive Outcome in Intracranial Germ Cell Tumor Survivors.

BACKGROUND: Childhood intracranial germ cell tumor (GCT) survivors are prone to radiotherapy-related neurotoxicity, which can lead to neurocognitive dysfunctions. Diffusion kurtosis imaging (DKI) is a diffusion MRI technique that is sensitive to brain microstructural changes. This study aimed to investigate the association between DKI metrics versus cognitive and functional outcomes of childhood intracranial GCT survivors. METHODS: DKI was performed on childhood intracranial GCT survivors (n = 20) who had received cranial radiotherapy, and age and gender-matched healthy control subjects (n = 14). Neurocognitive assessment was performed using the Hong Kong Wechsler Intelligence Scales, and functional assessment was performed using the Lansky/Karnofsky performance scales (KPS). Survivors and healthy controls were compared using mixed effects model. Multiple regression analyses were performed to determine the effects of microstructural brain changes of the whole brain as well as the association between IQ and Karnofsky scores and the thereof. RESULTS: The mean Intelligence Quotient (IQ) of GCT survivors was 91.7 (95% CI 84.5 - 98.8), which was below the age-specific normative expected mean IQ (P = 0.013). The mean KPS score of GCT survivors was 85.5, which was significantly lower than that of controls (P < 0.001). Cognitive impairments were significantly associated with the presence of microstructural changes in white and grey matter, whereas functional impairments were mostly associated with microstructural changes in white matter. There were significant correlations between IQ versus the mean diffusivity (MD) and mean kurtosis (MK) of specific white matter regions. The IQ scores were negatively correlated with the MD of extensive grey matter regions. CONCLUSION: Our study identified vulnerable brain regions whose microstructural changes in white and grey matter were significantly associated with impaired cognitive and physical functioning in survivors of pediatric intracranial GCT.

Suitability evaluation on material specifications and edible methods of Dendrobii Officinalis Caulis based on holistic polysaccharide marker.

BACKGROUND: Dendrobii Officinalis Caulis (DC) is a well-known tonic herbal medicine worldwide and has favorable immunomodulatory activity. Various material specifications of DC are available in herbal markets, and DC is ingested by different edible methods. However, whether these specifications and edible methods are suitable or not remains unknown. METHODS: In this study, we evaluated the suitability of four material specifications (fresh stem, dried stem, fengdou and powder) and three edible methods (making tea, soup and medicinal liquor) based on holistic polysaccharide marker (HPM), the major polysaccharide components in DC. First, the HPMs were extracted from the four specifications of DC by the three edible methods in different conditions. Second, qualitative and quantitative characterization of the extracted HPMs was performed using high performance gel permeation chromatography (HPGPC). Third, immunomodulatory activities of the extracted HPMs were evaluated in vivo. RESULTS: The results showed that the HPMs were found to be quantitatively different from various specification of DC and edible methods. In vivo analysis indicated that the HPMs exerted positive effects on innate immune responses by increment in proliferation of splenocytes, secretion of IL-2 and cytotoxicity activity of NK cells. Moreover, the dosage amount of HPM should be defined as a certain range, but not the larger the better, for exerting strong immunological activities. CONCLUSION: According to the both chemical and biological results, fengdou by boiling with water for 4 h is the most recommended specification and edible method for DC.

Stronger anti-obesity effect of white ginseng over red ginseng and the potential mechanisms involving chemically structural/compositional specificity to gut microbiota.

BACKGROUND: Ginseng has therapeutic potential for treating obesity and the associated gut microbiota dysbiosis. However, whether white ginseng and red ginseng, the two kinds of commonly used processed ginseng, possess different anti-obesity effects remains unknown. PURPOSE: Anti-obesity effects of water extracts of white ginseng and red ginseng (WEWG and WERG) were compared, and the potential mechanisms were discussed. METHODS: Chemical profiles of WEWG and WERG were characterized by ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS) and high performance liquid chromatography coupled with evaporative light scattering detector (HPLC-ELSD). Anti-obesity effects of WEWG/WERG were examined by determining fat accumulation, systemic inflammation, enteric metabolic disorders and gut microbiota dysbiosis in high-fat diet (HFD)-fed obese mice. RESULTS: Both WEWG and WERG exerted anti-obesity effects, with WEWG stronger than WERG. Compared to WERG, WEWG contained less contents of carbohydrates (polysaccharides, oligosaccharides, free monosaccharides) and ginsenosides, but chemical structures or compositions of these components in WEWG were characteristic, i.e. narrower molecular weight distribution and higher molar ratios of glucose residues of polysaccharides; higher content ratios of oligosaccharides DP2-3 (di-/tri-saccharides)-to-oligosaccharides DP4-7 (tetra-/penta-/hexa-/hepta-saccharides), sucrose-to-melibiose, maltose-to-trehalose and high-polar-to-low-polar ginsenosides. WEWG better ameliorated fat accumulation, enteric metabolic disorders and gut microbiota dysbiosis in HFD-fed obese mice than WERG. CONCLUSION: The stronger anti-obesity effect of white ginseng appears to correlate with differences in its chemical profile as compared to red ginseng. The carbohydrates and ginsenosides in WEWG potentially present more structural and compositional specificity to the obesity-associated gut bacteria, allowing more beneficial effects of WEWG on the gut microbiota dysbiosis. This consequently better alleviates the enteric metabolic disorders and systemic inflammation, thereby contributing to the stronger anti-obesity effect of WEWG as compared to WERG.