Effects of time-restricted feeding with different feeding windows on metabolic health: A systematic review of human studies.

Time-restricted feeding (TRF), a feasible form of intermittent fasting, has been proven to benefit metabolic health in animal models and humans. TRF restricts the daily feeding window to 3 to 12 h for eating ad libitum, with fasting for the rest of the day. To our knowledge, specific guidance on the appropriate time period for eating during TRF has not yet been promoted. Therefore, the aim of the present review was to summarize the current literature on the effects of TRF with different eating windows in humans and compare their effects on metabolic health-related markers. Early TRF (which restricts food intake during the early period of the day) and delayed TRF (which restricts food intake during the later period of the day) studies have shown that both TRF regimens improve metabolic health in terms of reducing energy intake, decreasing body weight, improving insulin sensitivity, reducing blood pressure, and reducing oxidative stress. Differences between the consequences of early and delayed TRF were found, including differences in changes in blood lipid factors. These preliminary findings may help to provide guidance for choosing suitable eating windows during TRF. Future studies with rigorous designs and direct comparisons between the effects of TRF regimens with different eating windows on metabolic health markers are still needed.

Randomized controlled trial for time-restricted eating in healthy volunteers without obesity.

Time-restricted feeding (TRF) improves metabolic health. Both early TRF (eTRF, food intake restricted to the early part of the day) and mid-day TRF (mTRF, food intake restricted to the middle of the day) have been shown to have metabolic benefits. However, the two regimens have yet to be thoroughly compared. We conducted a five-week randomized trial to compare the effects of the two TRF regimens in healthy individuals without obesity (ChiCTR2000029797). The trial has completed. Ninety participants were randomized to eTRF (n=30), mTRF (n=30), or control groups (n=30) using a computer-based random-number generator. Eighty-two participants completed the entire five-week trial and were analyzed (28 in eTRF, 26 in mTRF, 28 in control groups). The primary outcome was the change in insulin resistance. Researchers who assessed the outcomes were blinded to group assignment, but participants and care givers were not. Here we show that eTRF was more effective than mTRF at improving insulin sensitivity. Furthermore, eTRF, but not mTRF, improved fasting glucose, reduced total body mass and adiposity, ameliorated inflammation, and increased gut microbial diversity. No serious adverse events were reported during the trial. In conclusion, eTRF showed greater benefits for insulin resistance and related metabolic parameters compared with mTRF. Clinical Trial Registration URL: http://www.chictr.org.cn/showproj.aspx?proj=49406 .

Chemical Reactivities of Two Widely Used Ruthenium-Based CO-Releasing Molecules with a Range of Biologically Important Reagents and Molecules.

Ruthenium-based CO-releasing molecules (CO-RMs), CORM-2 and CORM-3, have been widely used as surrogates of CO for studying its biological effects in vitro and in vivo with much success. However, several previous solution-phase and in vitro studies have revealed the ability of such CO-RMs to chemically modify proteins and reduce aromatic nitro groups due to their intrinsic chemical reactivity under certain conditions. In our own work of studying the cytoprotective effects of CO donors, we were in need of assessing chemical factors that could impact the interpretation of results from CO donors including CORM-2,3 in various in vitro assays. For this, we examined the effects of CORM-2,3 toward representative reagents commonly used in various bioassays including resazurin, tetrazolium salts, nitrites, and azide-based H2S probes. We have also examined the effect of CORM-2,3 on glutathione disulfide (GSSG), which is a very important redox regulator. Our studies show the ability of these CO-RMs to induce a number of chemical and/or spectroscopic changes for several commonly used biological reagents under near-physiological conditions. These reactions/spectroscopic changes cannot be duplicated with CO-deleted CO-RMs (iCORMs), which are often used as negative controls. Furthermore, both CORM-2 and -3 are capable of consuming and reducing GSSG in solution. We hope that the results described will help in the future design of control experiments using Ru-based CO-RMs.

The beneficial effects of intermittent fasting: an update on mechanism, and the role of circadian rhythm and gut microbiota.

IMPORTANCE: There is accumulating evidence that intermittent fasting (IF) is connected to improved health condition and longevity time-restricted feeding (TRF) is the most recognized and extensively studied model of IF. OBJECTIVE: To investigate the underlying mechanism of pleiotropic benefits of IF and hint the most advantageous feeding pattern for humans. EVIDENCE REVIEW: We searched MEDLINE, EMBASE, Cochrane Library and Google Scholar by 2020 April for publications on IF or TRF and their mechanisms. Studies include animal models and human cohorts. FINDINGS: One important mechanism is that IF allows certain period of fasting time, in which our bodies activate pathways of repair and rejuvenation. Moreover, the advantages of IF, especially TRF over total caloric restriction (CR) provided bases for various animal and human studies which suggested that the feeding-fasting rhythm stimulates the fluctuation of our gut microbiota and a series of subsequent molecular alterations, which in turn restored a healthier circadian clock that resembled our inherent clock formed throughout millions of years of homo sapiens history. CONCLUSIONS AND RELEVANCE FOR REVIEWS: Complete understanding of the mechanism leading to the beneficial effects of IF paves the way for tailored dietary regimen to combat a wide range of diseases and ill health conditions.

Anterior chest wall in SAPHO syndrome: magnetic resonance imaging findings.

BACKGROUND: The anterior chest wall (ACW) involvement is characteristic of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, yet little research has focused on its magnetic resonance imaging (MRI) findings. PURPOSE: To characterize the MRI features of the ACW in patients with SAPHO syndrome. METHODS: Seventy-one patients with SAPHO syndrome and ACW involvement evidenced by bone scintigraphy were recruited in this cross-sectional study. The ACW region was scanned using sagittal, axial, and oblique coronal Dixon T2-weighted sequences and axial Dixon T1-weighted sequences. The characteristics of both active inflammatory and chronic structural lesions were evaluated. RESULTS: The ACW lesions exhibited an asymmetrical distribution and a predilection for the sternocostoclavicular region (93.0%). Notably, 91.5% of the patients had lesions in the area of the anterior first ribs. Bone marrow edema (BME) was observed in 63 (88.7%) patients, which mainly affected the sternocostal joints (87.3%) and the manubrium sterni (84.5%). All of the BMEs were distributed under the articular surface or the bone cortex, consistent with the distribution of the ligaments and joint capsules. Synovitis was detected in 64 (90.1%) patients, with a predilection for the sternoclavicular joints (76.1%). A soft tissue mass or infiltration was found in all the patients who had bone marrow edema. Thirteen (18.3%) patients showed venous stenosis. Structural changes included bone bridge formation (80.3%), hyperostosis (43.7%), and fat infiltration (39.4%). Four common patterns of involvement were observed: the first rib area, the sternoclavicular area, the sternal angle area, and the areas of the second to sixth sternocostal joints. CONCLUSION: The ACW lesions of SAPHO syndrome demonstrated a triad of enthesitis, synovitis, and osteitis, suggesting complex interactions among the ligaments, synovium, and bones in the region. The inflammatory changes in the first rib area were highlighted in SAPHO syndrome.

Axial skeletal lesions and disease duration in SAPHO syndrome: A retrospective review of computed tomography findings in 81 patients.

AIMS: To explore the relevance of disease duration with axial skeletal lesions in synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome based on computed tomography (CT). METHODS: Patients who had undergone whole-spine CT were included from a previously reported single-center cohort of SAPHO syndrome. Patients with previous treatments of bisphosphates, biological agents or surgeries were excluded. Sites of axial skeletal involvement were reviewed including the spine, sacroiliac joints, and anterior chest wall. Duration of osteoarticular involvement was defined as the interval between the onset of osteoarticular symptoms and the CT evaluation. RESULTS: Eighty-one patients (54 female and 27 male) were included in the study. The mean disease duration was 26.9 ± 34.9 months. Fifty (63.0%) patients showed spinal lesions on CT. The average numbers of involved vertebral segments for corner and endplate lesions were 3.16 ± 3.51 and 0.73 ± 1.85 respectively. Sixty-eight (84.0%) patients exhibited abnormalities in the anterior chest wall. The number of involved vertebral segments showed poor correlation with disease duration for both corner lesions (r2  = 0.051, P = 0.043) and endplate lesions (r2  = 0.137, P = 0.001). Patients with costoclavicular involvement showed remarkably longer disease duration than those without (49.3 ± 47.7 months vs 18.0 ± 23.5 months, P = 0.006), while no significant difference was detected regarding other structures in the anterior chest wall. CONCLUSION: Costoclavicular involvement is a hallmark of long disease duration in SAPHO syndrome. Corner and endplate lesions in the vertebrae and sacroiliac involvement may not relate to disease course.

Time-Restricted Feeding Reduces the Detrimental Effects of a High-Fat Diet, Possibly by Modulating the Circadian Rhythm of Hepatic Lipid Metabolism and Gut Microbiota.

Background: Time-restricted feeding, also known as intermittent fasting, can confer various beneficial effects, especially protecting against obesity, and related metabolic disorders, but little is known about the underlying mechanisms. Therefore, the present study aims to investigate the effects of time-restricted feeding on the circadian rhythm of gut microbiota and hepatic metabolism. Methods: Eight-week-old male Kunming mice received either a normal diet ad libitum, a high-fat diet ad libitum, or a high-fat diet restricted to an 8-h temporal window per day for an experimental period of 8 weeks. Weight gain and calorie intake were measured weekly. Serum metabolites, hepatic sections and lipid metabolites, gut microbiota, and the hepatic expression of Per1, Cry1, Bmal1, SIRT1, SREBP, and PPARα were measured at the end of the experimental period. The composition of gut microbiota and the expression of hepatic genes were compared between four timepoints. Results: Mice that received a time-restricted high-fat diet had less weight gain, milder liver steatosis, and lower hepatic levels of triglycerides than mice that received a high-fat diet ad libitum (p < 0.05). The numbers of Bacteroidetes and Firmicutes differed between mice that received a time-restricted high-fat diet and mice that received a high-fat diet ad libitum (p < 0.05). Mice fed a time-restricted high-fat diet showed distinct circadian rhythms of hepatic expression of SIRT1, SREBP, and PPARα compared with mice fed a normal diet ad libitum, as well as the circadian rhythm of the abundance of Bacteroidetes and Firmicutes. Conclusions: Time-restricted feeding is associated with better metabolic conditions, perhaps owing to alterations in gut microbiota and the circadian pattern of molecules related to hepatic lipid metabolism, which were first to report.

Time-restricted feeding during childhood has persistent effects on mice commensal microbiota.

BACKGROUND: Time-restricted feeding (TRF) has been proved to improve general health in adults. However, according to our previous study, this regimen failed to show similar protective effect in pediatric population. Gut microbiota has been proved to play a vital part in the whole process. Although previous studies have defined the commensal flora as a real-time indicator of health conditions in adults, our study aimed to investigate whether the unfavorable TRF feeding schedule during childhood would cause long-term variations in murine model. METHODS: We randomly assigned 120 4-week-old Kunming mice (half male and half female) to four feeding regimens: TRF.AD, time-restricted feeding during the childhood phase before switched to ad libitum feeding pattern as adults; TRF.TRF, continuously treated with time-restricted feeding; AD.TRF, went through time-restricted feeding only in adulthood; AD.AD, always had ad libitum access to food. After 8 weeks of dietary intervention, faeces were harvested from 12-week-old adult mice (one subject per cage), and gut microbiota was subsequently analysed via DNA extraction and 16s rRNA sequencing. RESULTS: Mice on identical diet for four weeks but went through different feeding patterns during childhood showed distinctive traits in gut microbiota. Differences existed in both the α diversity and specific groups of bacteria under different taxonomical levels. CONCLUSIONS: Feeding pattern in the childhood had long-term impact on mice gut flora that cannot be wiped out in adulthood.

Genotypic and phenotypic characterization of Chinese patients with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a rare hereditary skeletal dysplasia, characterized by recurrent fractures and bone deformity. This study presents a clinical characterization and mutation analysis of 668 patients, aiming to establish the mutation spectrum and to elucidate genotype-phenotype correlations in Chinese OI patients. We identified 274 sequence variants (230 in type I collagen encoding genes and 44 in noncollagen genes), including 102 novel variants, in 340 probands with a detection rate of 90%. Compared with 47 loss-of-function variants detected in COL1A1, neither nonsense nor frameshift variants were found in COL1A2 (p < 0.0001). The major cause of autosomal recessive OI was biallelic variants in WNT1 (56%, 20/36). It is noteworthy that three genomic rearrangements, including one gross deletion and one gross duplication in COL1A1 as well as one gross deletion in FKBP10, were detected in this study. Of ten individuals with glycine substitutions that lie towards the N-terminal end of the triple-helical region of the α1(I) chain, none exhibited hearing loss, suggesting a potential genotype-phenotype correlation. The findings in this study expanded the mutation spectrum and identified novel correlations between genotype and phenotype in Chinese OI patients.

Coherent perfect absorption in chiral metamaterials.

We study the coherent perfect absorption (CPA) of a chiral structure and derive analytically the CPA condition for transversely isotropic chiral structures in circular polarization bases. The coherent absorption of such a chiral system is generally polarization dependent and can be tuned by the relative phase between the coherent input beams. To demonstrate our theoretical predictions, a chiral metamaterial absorber operating in the terahertz frequency range is optimized. We numerically demonstrate that a coherent absorption of 99.5% can be achieved. Moreover, we show that an optimized CPA chiral structure can be used as an interferometric control of polarization state of the output beams with constant output intensity.

Rapid probing of sialylated glycoproteins in vitro and in vivo via metabolic oligosaccharide engineering of a minimal cyclopropene reporter.

ManNAc analogues are important chemical tools for probing sialylation dynamically via metabolic oligosaccharide engineering (MOE). The size of N-acyl and the nature of the chemical handle are two determinants of metabolic incorporation efficiency. We demonstrated a minimal, stable, bioorthogonal, and reactive N-Cp (N-(cycloprop-2-ene-1-ylcarbonyl)) group and the imaging of sialylated glycans using Ac4ManNCp in vitro and in vivo. The results revealed that the Cp group can efficiently be incorporated into the cellular sialic acid and detected rapidly by the reaction with FITC-Tz in different cells. The metabolic incorporation efficiency of non-cytotoxic Ac4ManNCp is not only superior to Ac4ManNMCp, but also superior to the widely-used Ac4ManNAz in some cell lines. Moreover, when Ac4ManNCp was administered to mice, a rapid and intense labelling of splenocytes as well as glycoproteins of sera and organs was observed. This is the first reported metabolic labelling of cyclopropene-modified sugars in vivo. Therefore, Ac4ManNCp is a powerful probe for efficient and rapid MOE and it may find wide applications in the labelling of glycans.

Circular polarization selective microcavity by using gold helix array.

A circular polarization selective microcavity using chiral photonic metamaterials is designed, in which photons of a particular circular polarization dominate in stimulated emissions as a result of cavity resonances. The selection behavior originates from the special chiral reflector, which exhibits two elliptical polarization eigenstates almost identical to the same circular polarization. Theoretical analysis by using Jones matrix is given to explain this interesting phenomenon in detail. A lasing mode with an almost perfect circularly polarized field is present inside this cavity and observable at the output.

Evolution of Airy beams in a chiral medium.

We study the evolution of Airy beams in chiral media. We numerically demonstrate that the circularly polarized Airy beams of opposite handedness can be separated when traveling through the chiral media. The constructive interference of the Airy beams in the near- and far-zone is explicitly analyzed by varying the chirality parameter of the medium. It is interesting to find that the self-acceleration of the beam is sensitive to the interference term.