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 decade
. 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 proteins
. 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 resolution
). 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.
The COVID-19 pandemic has impacted the psychological health and health service utilisation of older adults with multimorbidity, who are particularly vulnerable.
To describe changes in loneliness, ...mental health problems, and attendance to scheduled medical care before and after the onset of the COVID-19 pandemic.
Telephone survey on a pre-existing cohort of older adults with multimorbidity in primary care.
Mental health and health service utilisation outcomes were compared with the outcomes before the onset of the COVID-19 outbreak in Hong Kong using paired
-tests, Wilcoxon's signed-rank test, and McNemar's test. Loneliness was measured by the De Jong Gierveld Loneliness Scale. The secondary outcomes (anxiety, depression, and insomnia) were measured by the 9-item Patient Health Questionnaire, the 7-item Generalized Anxiety Disorder tool, and the Insomnia Severity Index. Appointments attendance data were extracted from a computerised medical record system. Sociodemographic factors associated with outcome changes were examined by linear regression and generalised estimating equations.
Data were collected from 583 older (≥60 years) adults. There were significant increases in loneliness, anxiety, and insomnia, after the onset of the COVID-19 outbreak. Missed medical appointments over a 3-month period increased from 16.5% 1 year ago to 22.0% after the onset of the outbreak. In adjusted analysis, being female, living alone, and having >4 chronic conditions were independently associated with increased loneliness. Females were more likely to have increased anxiety and insomnia.
Psychosocial health of older patients with multimorbidity markedly deteriorated and missed medical appointments substantially increased after the COVID-19 outbreak.
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.
WEG showed strong anti-EF effects by the beneficial effects of saccharides and ginsenosides on gut microbiota, then energy metabolism abnormality, lipid peroxidation and metabolic disorder as well as inflammatory response.
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.
Anti-obesity effects of water extracts of white ginseng and red ginseng (WEWG and WERG) were compared, and the potential mechanisms were discussed.
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.
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.
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.
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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;
= 577), during school closures (March 2020-April 2020;
= 146), and after schools partially reopened (October 2020-July 2021;
= 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.
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.
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.
Exposure of magnolol causes mitochondrial dysfunction which induces mitophagy and intrinsic apoptosis. Inhibition of autophagy/mitophagy by distinct inhibitors at different stages promotes cell death and tumor suppression evidenced by further reduction of tumor volume and weight. Display omitted
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 P
and P
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.
Background and Aim
In registration studies, combination therapy of paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) with and without ribavirin for 12–24 weeks can achieve > 90% sustained ...virological response (SVR) for genotype 1 hepatitis C virus (HCV) infection. However, data in Asia is scanty. We aimed to study the efficacy and safety of this combination therapy in chronic hepatitis C patients in Hong Kong.
Methods
We retrospectively analyzed data from six local hospitals that have prescribed PrOD with and without ribavirin to patients with genotype 1 chronic HCV infection as part of a global compassionate program.
Results
Among 41 patients treated, 35 (85%) patients had genotype 1b HCV infection, 6 (15%) had co‐infection with human immunodeficiency virus, 35 (85%) failed previous peginterferon and ribavirin therapy, 25 (61%) had compensated liver cirrhosis, and 3 (7%) had liver transplantation. Thirty‐five (85%) patients received 12‐week treatment and six patients received 24‐week treatment; 26 (63%) patients received ribavirin combination. Thirty‐nine (95%; 95% confidence interval 88.5–100%) patients had undetectable HCV RNA at 12‐week post‐treatment, that is, SVR. The two patients who did not develop SVR discontinued treatment prematurely; both of them were treatment experienced with liver cirrhosis complicated by acute renal failure unrelated to the treatment of PrOD and ribavirin. No patient had hepatic decompensation.
Conclusions
Paritaprevir/ritonavir, ombitasvir, and dasabuvir with or without ribavirin is effective and safe in patients with genotype 1 HCV infection in real‐life clinical setting in Hong Kong.
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.
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.
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.
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.
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