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BackgroundAnkylosing spondylitis(AS) is a chronic inflammatory rheumatic disease that leads to a reduced quality of life. Exercise appears to be one of the promising modes of intervention. The aim of this study was to review the available evidence and compare the effectiveness of different exercises in relieving symptoms of AS.MethodsWe searched the Pubmed, WOS, EMbase, CNKI, Cochrane Library, and Scopus databases. The search has spanned from the creation of the database until September 15, 2023. We extracted the first author, year of article publication, sample information, intervention, duration of intervention, and outcome indicators from the literature that met the inclusion criteria. The Cochrane Risk Assessment Tool was used to assess the risk of bias for included studies. I² was used to judge the consistency of the included studies. Egger's test and Begg's test were used to judge whether there was significant publication bias. Forest plots were used to compare intervention effects and SUCRA was provided to rank the effects of the interventions. This study has been registered in PROSPERO(No. CRD42024518522).ResultsAfter screening, 10 papers matched the inclusion criteria for this study, and the total sample size of the 10 papers was 623. Upon analysis, the papers included in this study did not have significant publication bias (Begg's Test P = 0.210) and had good consistency (P>0.05). The direct comparisons showed that Running, Pilates, Stretching, Yoga, and Tai Chi were more effective interventions than traditional therapies. The effect sizes, confidence intervals, and number of studies for each intervention are shown below: Running [MD -1.90 (95% CI -3.14,-0.66) n = 1], Pilates [MD -1.70 (95% CI -2.90,-0.51) n = 1], Stretching [MD -1.54 (95% CI -2.21,-0.88) n = 4], Yoga [MD -1.24 (95% CI -2.18,-0.30) n = 1], Tai Chi [MD -0.78 (95% CI -1.44,-0.12) n = 2], Exergame[MD -0.80 (95% CI -1.99,0.39) n = 1], Swiss balls[MD -1.07 (95% CI -2.58,0.44) n = 1]. The indirect comparisons showed that the range of effect sizes for each sport intervention intersected the null line. Based on cumulative probability, the order of effectiveness of different exercises in relieving AS symptoms is Running, Pilates, Stretching, Yoga, Tai Chi, Exergame, and Swiss ball.ConclusionRunning, Pilates, Stretching, Yoga, and Tai Chi provided significant relief from AS symptoms. Exergame and Swiss ball were not statistically significant in relieving AS symptoms. There were no significant differences in the effectiveness of different exercise interventions in relieving AS symptoms. Running may have the most beneficial effect on alleviating AS symptoms.

ObjectiveAllopregnanolone (Allo) is a neurosteroid with pleiotropic action in the brain that includes neurogenesis, oligogenesis, human and rodent neural stem cell regeneration, increased glucose metabolism, mitochondrial respiration and biogenesis, improved cognitive function, and reduction of both inflammation and Alzheimer’s disease (AD) pathology. Because the breadth of Allo-induced responses requires activation of multiple systems of biology in the absence of an Allo-specific nuclear receptor, analyses were conducted in both neurons and astrocytes to identify unifying systems and signaling pathways.MethodsMechanisms of Allo action were investigated in embryonic hippocampal neurons and astrocytes cultured in an Aging Model (AM) media. Cellular morphology, mitochondrial function, and transcriptomics were investigated followed by mechanistic pathway analyses.ResultsIn hippocampal neurons, Allo significantly increased neurite outgrowth and synaptic protein expression, which were paralleled by upregulated synaptogenesis and long-term potentiation gene expression profiles. Mechanistically, Allo induced Ca2+/CREB signaling cascades. In parallel, Allo significantly increased maximal mitochondrial respiration, mitochondrial membrane potential, and Complex IV activity while reducing oxidative stress, which required both the GABAA and L-type Ca2+ channels. In astrocytes, Allo increased ATP generation, mitochondrial function and dynamics while reducing oxidative stress, inflammasome indicators, and apoptotic signaling. Mechanistically, Allo regulation of astrocytic mitochondrial function required both the GABAA and L-type Ca2+ channels. Furthermore, Allo activated NRF1-TFAM signaling and increased the DRP1/OPA1 protein ratio, which led to increased mitochondrial biogenesis and dynamics.ConclusionCollectively, the cellular, mitochondrial, transcriptional, and pharmacological profiles provide evidence in support of calcium signaling as a unifying mechanism for Allo pleiotropic actions in the brain.

Maize silage has a high demand for fertilizer and water. As an unconventional feed resource, mulberry silage has the potential to replace most maize silage and to alleviate the shortage of roughage in the mutton sheep industry in China. The purpose of this experiment was to study the effect of the replacement of maize silage and soyabean meal with mulberry silage in the diet of Hu lambs on growth performance, serum biochemical indices, slaughter performance, and meat quality. Ninety-six healthy Hu lambs were randomly divided into four groups with six replicates per group and four lambs per replicate. The amounts of 0, 20, 40, and 60% of maize silage were replaced by mulberry silage in each group (denoted as CON, L, M, and H, respectively). The results showed that replacing maize silage with mulberry silage had no significant effect on the growth performance or the slaughter performance of Hu lambs (p > 0.05). Feeding Hu lambs with mulberry silage significantly reduced serum glucose (GLU) and the blood urea nitrogen (BUN) content (p < 0.05), and it increased the content of ether extract (EE) in the longissimus dorsi muscle (p < 0.05). Meanwhile, the percentage of EAA in the M and H groups was significantly lower than that in the CON and L groups (p < 0.05). In addition, in the fatty acid profile, the percentage of C16:1 in the M group was significantly increased, while the percentage of C18:0 and C20:0 were significantly decreased (p < 0.05). Based on these findings, it was recommended that 20–40% of maize silage be replaced by mulberry silage in the diet of Hu lambs.

Summary: Aging and endocrine transition states can significantly impact inflammation across organ systems. Neuroinflammation is well documented in Alzheimer disease (AD). Herein, we investigated neuroinflammation that emerges during mid-life aging, chronological and endocrinological, in the female brain as an early initiating mechanism driving AD risk later in life. Analyses were conducted in a translational rodent model of mid-life chronological and endocrinological aging followed by validation in transcriptomic profiles from women versus age-matched men. In the translational model, the neuroinflammatory profile of mid-life aging in females was endocrine and chronological state specific, dynamic, anatomically distributed, and persistent. Microarray dataset analyses of aging human hippocampus indicated a sex difference in neuroinflammatory profile in which women exhibited a profile comparable to the pattern discovered in our translational rodent model, whereas age-matched men exhibited a profile consistent with low neuroimmune activation. Translationally, these findings have implications for therapeutic interventions during mid-life to decrease late-onset AD risk.

Maize silage has a significant environmental impact on livestock due to its high requirement for fertilizer and water. Mulberry has the potential to replace much of the large amount of maize silage grown in China, but its feeding value in the conserved form needs to be evaluated. We fed Hu lambs diets with 20–60% of the maize silage replaced by mulberry silage, adjusting the soybean meal content when increasing the mulberry silage inclusion rate in an attempt to balance the crude protein content of the diets. Mulberry silage had higher crude protein and lower acidic and neutral detergent fiber contents compared to maize silage. Replacing maize silage and soyabean meal with mulberry silage had no effect on the feed intake and growth rate of Hu lambs. However, the rumen pH increased, the acetate to propionate in rumen fluid increased, and the rumen ammonia concentration decreased as mulberry replaced maize silage and soyabean meal. This was associated with an increase in norank_f__F082 bacteria in the rumen. Rumen papillae were shorter when mulberry silage replaced maize silage, which may reflect the reduced neutral detergent fiber (NDF) content of the original silage. In conclusion, mulberry silage can successfully replace maize silage and soyabeans in the diet of Hu lambs without loss of production potential, which could have significant environmental benefits.

Late onset Alzheimer's disease (LOAD) is a progressive neurodegenerative disease with four well-established risk factors: age, APOE4 genotype, female chromosomal sex, and maternal history of AD. Each risk factor impacts multiple systems, making LOAD a complex systems biology challenge. To investigate interactions between LOAD risk factors, we performed multiple scale analyses, including metabolomics, transcriptomics, brain magnetic resonance imaging (MRI), and beta-amyloid assessment, in 16 months old male and female mice with humanized human APOE3 (hAPOE3) or APOE4 (hAPOE4) genes. Metabolomic analyses indicated a sex difference in plasma profile whereas APOE genotype determined brain metabolic profile. Consistent with the brain metabolome, gene and pathway-based RNA-Seq analyses of the hippocampus indicated increased expression of fatty acid/lipid metabolism related genes and pathways in both hAPOE4 males and females. Further, female transcription of fatty acid and amino acids pathways were significantly different from males. MRI based imaging analyses indicated that in multiple white matter tracts, hAPOE4 males and females exhibited lower fractional anisotropy than their hAPOE3 counterparts, suggesting a lower level of white matter integrity in hAPOE4 mice. Consistent with the brain metabolomic and transcriptomic profile of hAPOE4 carriers, beta-amyloid generation was detectable in 16-month-old male and female brains. These data provide therapeutic targets based on chromosomal sex and APOE genotype. Collectively, these data provide a framework for developing precision medicine interventions during the prodromal phase of LOAD, when the potential to reverse, prevent and delay LOAD progression is greatest.

The PSD-95/SAPAP/Shank complex functions as the major scaffold in orchestrating the formation and plasticity of the post-synaptic densities (PSDs). We previously demonstrated that the exquisitely specific SAPAP/Shank interaction is critical for Shank synaptic targeting and Shank-mediated synaptogenesis. Here, we show that the PSD-95/SAPAP interaction, SAPAP synaptic targeting, and SAPAP-mediated synaptogenesis require phosphorylation of the N-terminal repeat sequences of SAPAPs. The atomic structure of the PSD-95 guanylate kinase (GK) in complex with a phosphor-SAPAP repeat peptide, together with biochemical studies, reveals the molecular mechanism underlying the phosphorylation-dependent PSD-95/SAPAP interaction, and it also provides an explanation of a PSD-95 mutation found in patients with intellectual disabilities. Guided by the structural data, we developed potent non-phosphorylated GK inhibitory peptides capable of blocking the PSD-95/SAPAP interaction and interfering with PSD-95/SAPAP-mediated synaptic maturation and strength. These peptides are genetically encodable for investigating the functions of the PSD-95/SAPAP interaction in vivo.

The Eph receptor tyrosine kinase (RTK) family is the largest subfamily of RTKs playing critical roles in many developmental processes such as tissue patterning, neurogenesis and neuronal circuit formation, angiogenesis, etc. How the 14 Eph proteins, via their highly similar cytoplasmic domains, can transmit diverse and sometimes opposite cellular signals upon engaging ephrins is a major unresolved question. Here, we systematically investigated the bindings of each SAM domain of Eph receptors to the SAM domains from SHIP2 and Odin, and uncover a highly specific SAM–SAM interaction-mediated cytoplasmic Eph-effector binding pattern. Comparative X-ray crystallographic studies of several SAM–SAM heterodimer complexes, together with biochemical and cell biology experiments, not only revealed the exquisite specificity code governing Eph/effector interactions but also allowed us to identify SAMD5 as a new Eph binding partner. Finally, these Eph/effector SAM heterodimer structures can explain many Eph SAM mutations identified in patients suffering from cancers and other diseases.

Abstract Background With the recent certification by World Health Organization that the People’s Republic of China is malaria-free, it is timely to consider how elimination of malaria was completed in People’s Republic of China over the last 7 decades. Of the four widespread species of human malaria, Plasmodium vivax was the last to be eliminated by the national program of China. Understanding the incubation periods and relapses patterns of P. vivax through historical data from China is relevant for planning disease elimination in other malaria-endemic countries, with residual P. vivax malaria. Methods We collated data from both published and unpublished malaria parasite inoculation experiments conducted between 1979 and 1988 with parasites from different regions of the People’s Republic of China. The studies had at least two years of follow-up. We categorized P. vivax incubation patterns via cluster analysis and investigated relapse studies by adapting a published within-host relapse model for P. vivax temperate phenotypes. Each model was fitted using the expectation-maximization (EM) algorithm initialized by hierarchical model-based agglomerative clustering. Results P. vivax parasites from the seven studies of five southern and central provinces in the People’s Republic of China covering geographies ranging from the south temperate to north tropical zones. The parasites belonged to two distinct phenotypes: short- (10–19 days) or long-incubation (228–371 days). The larger the sporozoite inoculation, the more likely short incubation periods were observed, and with more subsequent relapses (Spearman’s rank correlation between the number of inoculated sporozoites and the number of relapses of 0.51, p-value = 0.0043). The median of the posterior distribution for the duration of the first relapse interval after primary infection was 168.5 days (2.5% quantile: 89.7; 97.5% quantile: 227.69 days). The predicted survival proportions from the within-host model fit well to the original relapse data. The within-host model also captures the hypnozoite activation rates and relapse frequencies, which consequently influences the transmission possibility of P. vivax. Conclusions Through a within-host model, we demonstrate the importance of clearance of hypnozoites. A strategy of two rounds of radical hypnozoite clearance via mass drug administration (MDA) deployed during transmission (summer and autumn) and non-transmission (late spring) seasons had a pronounced effect on outbreaks during the malaria epidemics in China. This understanding can inform malaria control strategies in other endemic countries with similar settings.

Achieving efficient multi-electron-involved photoreduction, e.g. the reduction of nitroaromatics to amines, remains challenging yet highly demanded. Two-dimensional (2D) covalent organic nanosheets (CONs) present promising platforms for such reactions due to their exceptional properties, including structural tunability and unique photoelectronic properties. Nevertheless, the exploration of CON-based composites for catalyzing organic reactions is still in its infancy, with examples of CONs acting as intrinsic catalysts being relatively scarce. In this study, we developed hybrid catalysts, denoted as T4-Mn/QA-CONs, by decorating anionic semiconductor clusters (T4-Mn) onto 2D cationic CONs (QA-CONs) via electrostatic self-assembly. Remarkably, T4-Mn/QA-CONs exhibited exceptional performance, achieving a 99% conversion rate and 100% selectivity with a turnover frequency (TOF) of 2.68 h−1 in the reduction of nitroarenes to amines under visible light irradiation. In addition, T4-Mn/QA-CONs demonstrated excellent stability and recyclability, along with remarkable functional group tolerance. The outstanding activity can be attributed to the effective charge separation facilitated by the photoinduced strong internal electric field and II-scheme mechanism, as confirmed by in situ X-ray photoelectron spectroscopy along with femtosecond transient absorption spectroscopy. This study presents a novel strategy for designing CONs as crucial catalytic centers and highlights the potential of CON-based heterojunction photocatalysts for efficient organic transformations. [ABSTRACT FROM AUTHOR]

Fluorescent carbon quantum dots (CQDs) were synthesized from cucurbit[7]uril (Q[7]) and 2,2-bis(hydroxymethyl)propionic (DMPA) by a hydrothermal method. The Q[7]–DMPA complex was confirmed by X-ray crystallography. The CQDs showed blue fluorescence, photostability, and ionic strength stability. They were used to detect histamine with a low limit of 2.33 × 10−6 M. [ABSTRACT FROM AUTHOR]

A facile strategy that directly reduces alkynyl‐silver precursors and copper salts for the synthesis of bimetallic nanoclusters using the weak reducing agent Ph2SiH2 is demonstrated. Two alkynyl‐protected concentric‐shell nanoclusters, (Ph4P)2[Ag22Cu12(C≡CR)28] and (Ph4P)3[Ag42Cu12Cl(C≡CR)36] (Ag22Cu12 and Ag42Cu12Cl, R=bis(trifluoromethyl)phenyl), were successfully obtained and characterized by single‐crystal X‐ray diffraction and electro‐spray ionization mass spectrometry. For the first time, a hybrid 55‐atom two‐shell Mackay icosahedron was found in Ag42Cu12Cl, which is icosahedral M54Cl instead of M55. The incorporation of a chloride in the metal icosahedron contributes to the stability of the cluster from both electronic and geometric aspects. Alkynyl ligands show various binding‐modes including linear "RC≡C−Cu−C≡CR" staple motifs. [ABSTRACT FROM AUTHOR]