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ObjectivesTo compare cognitive effects and acceptability of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) in patients with Alzheimer’s disease (AD) or mild cognitive impairment (MCI), and to determine whether cognitive training (CT) during rTMS or tDCS provides additional benefits.MethodsElectronic search of PubMed, Medline, Embase, the Cochrane Library and PsycINFO up to 5 March 2020. We enrolled double-blind, randomised controlled trials (RCTs). The primary outcomes were acceptability and pre–post treatment changes in general cognition measured by Mini-Mental State Examination, and the secondary outcomes were memory function, verbal fluency, working memory and executive function. Durability of cognitive benefits (1, 2 and ≥3 months) after brain stimulation was examined.ResultsWe included 27 RCTs (n=1070), and the treatment components included high-frequency rTMS (HFrTMS) and low-frequency rTMS, anodal tDCS (atDCS) and cathodal tDCS (ctDCS), CT, sham CT and sham brain stimulation. Risk of bias of evidence in each domain was low (range: 0%–11.1%). HFrTMS (1.08, 9, 0.35–1.80) and atDCS (0.56, 0.03–1.09) had short-term positive effects on general cognition. CT might be associated with negative effects on general cognition (−0.79, –2.06 to 0.48) during rTMS or tDCS. At 1-month follow-up, HFrTMS (1.65, 0.77–2.54) and ctDCS (2.57, 0.20–4.95) exhibited larger therapeutic responses. Separate analysis of populations with pure AD and MCI revealed positive effects only in individuals with AD. rTMS and tDCS were well tolerated.ConclusionsHFrTMS is more effective than atDCS for improving global cognition, and patients with AD may have better responses to rTMS and tDCS than MCI.

Age‐associated obesity and muscle atrophy (sarcopenia) are intimately connected and are reciprocally regulated by adipose tissue and skeletal muscle dysfunction. During ageing, adipose inflammation leads to the redistribution of fat to the intra‐abdominal area (visceral fat) and fatty infiltrations in skeletal muscles, resulting in decreased overall strength and functionality. Lipids and their derivatives accumulate both within and between muscle cells, inducing mitochondrial dysfunction, disturbing β‐oxidation of fatty acids, and enhancing reactive oxygen species (ROS) production, leading to lipotoxicity and insulin resistance, as well as enhanced secretion of some pro‐inflammatory cytokines. In turn, these muscle‐secreted cytokines may exacerbate adipose tissue atrophy, support chronic low‐grade inflammation, and establish a vicious cycle of local hyperlipidaemia, insulin resistance, and inflammation that spreads systemically, thus promoting the development of sarcopenic obesity (SO). We call this the metabaging cycle. Patients with SO show an increased risk of systemic insulin resistance, systemic inflammation, associated chronic diseases, and the subsequent progression to full‐blown sarcopenia and even cachexia. Meanwhile in many cardiometabolic diseases, the ostensibly protective effect of obesity in extremely elderly subjects, also known as the ‘obesity paradox’, could possibly be explained by our theory that many elderly subjects with normal body mass index might actually harbour SO to various degrees, before it progresses to full‐blown severe sarcopenia. Our review outlines current knowledge concerning the possible chain of causation between sarcopenia and obesity, proposes a solution to the obesity paradox, and the role of fat mass in ageing.

Plant-based diets, characterized by a higher consumption of plant foods and a lower consumption of animal foods, are associated with a favorable cardiovascular disease (CVD) risk, but evidence regarding the association between plant-based diets and CVD (including coronary heart disease (CHD) and stroke) incidence remain inconclusive. A literature search was conducted using the PubMed, EMBASE and Web of Science databases through December 2020 to identify prospective observational studies that examined the associations between plant-based diets and CVD incidence among adults. A systematic review and a meta-analysis using random effects models and dose–response analyses were performed. Ten studies describing nine unique cohorts were identified with a total of 698,707 participants (including 137,968 CVD, 41,162 CHD and 13,370 stroke events). Compared with the lowest adherence, the highest adherence to plant-based diets was associated with a lower risk of CVD (RR 0.84; 95% CI 0.79–0.89) and CHD (RR 0.88; 95% CI 0.81–0.94), but not of stroke (RR 0.87; 95% CI 0.73–1.03). Higher overall plant-based diet index (PDI) and healthful PDI scores were associated with a reduced CVD risk. These results support the claim that diets lower in animal foods and unhealthy plant foods, and higher in healthy plant foods are beneficial for CVD prevention. Protocol was published in PROSPERO (No. CRD42021223188).

Background Ageing, chronic diseases, prolonged inactivity, and inadequate nutrition pose a severe threat to skeletal muscle health and function. To date, experimental evidence suggests that ageing‐related subclinical inflammation could be an important causative factor in sarcopenia. Although inflammatory signalling has been implicated in the pathogenesis of experimental animal models of sarcopenia, few studies have surveyed the clinical association between circulating factors and muscle mass in patients before and after lifestyle interventions. In this study, we evaluated whether proinflammatory cytokines are associated with the onset of sarcopenia, which circulating factors are associated with the severity of sarcopenia, and how these factors change after lifestyle interventions in sarcopenic elderly persons. Methods A total of 56 elderly subjects (age ≥ 60 years) with sarcopenia and 56 elderly non‐sarcopenic subjects, who met entry criteria and had given informed consent, were selected from the Peking Union Medical College Hospital multicentre prospective longitudinal sarcopenia study for testing relevant circulating factors. Thirty‐two elderly subjects from the sarcopenic cohort completed a 12 week intensive lifestyle intervention programme with whey supplements (30 g/day) and a personalized resistance training regimen. The levels of proinflammatory cytokines and metabolic hormones, pre‐intensive and post‐intensive lifestyle interventions, were measured. Results The sarcopenic group was significantly older (72.05 ± 6.54 years; P < 0.001), more likely to be inactive and female (57.1% of all sarcopenic patients), and had a higher prevalence of type 2 diabetes (16% higher risk). Compared with non‐sarcopenic subjects, serum interleukin (IL)‐6, IL‐18, tumour necrosis factor‐α (TNF‐α), TNF‐like weak inducer of apoptosis (TWEAK), and leptin were significantly higher, while insulin growth factor 1, insulin, and adiponectin were significantly lower in sarcopenic patients (all P < 0.05). Logistic regression analyses revealed that high levels of TNF‐α (>11.15 pg/mL) and TWEAK (>1276.48 pg/mL) were associated with a 7.6‐fold and 14.3‐fold increased risk of sarcopenia, respectively. After adjustment for confounding variables, high levels of TWEAK were still associated with a 13.4‐fold increased risk of sarcopenia. Intensive lifestyle interventions led to significant improvements in sarcopenic patients' muscle mass and serum profiles of TWEAK, TNF‐α, IL‐18, insulin, and adiponectin (all P < 0.05). Conclusions High levels of the inflammatory cytokines TWEAK and TNF‐α are associated with an increased risk of sarcopenia, while the metabolic hormones insulin growth factor 1, insulin, and adiponectin are associated with a decreased risk of sarcopenia in our Chinese patient cohort. Intensive lifestyle interventions could significantly improve muscle mass, reduce inflammation, and restore metabolic hormone levels in sarcopenic patients. This trial was registered at clinicaltrials.gov as NCT02873676.

Background Crystalloids and different component colloids, used for volume resuscitation, are sometimes associated with various adverse effects. Clinical trial findings for such fluid types in different patients’ conditions are conflicting. Whether the mortality benefit of balanced crystalloid than saline can be inferred from sepsis to other patient group is uncertain, and adverse effect profile is not comprehensive. This study aims to compare the survival benefits and adverse effects of seven fluid types with network meta-analysis in sepsis, surgical, trauma, and traumatic brain injury patients. Methods Searched databases (PubMed, EMBASE, and Cochrane CENTRAL) and reference lists of relevant articles occurred from inception until January 2020. Studies on critically ill adults requiring fluid resuscitation were included. Intervention studies reported on balanced crystalloid, saline, iso-oncotic albumin, hyperoncotic albumin, low molecular weight hydroxyethyl starch (L-HES), high molecular weight HES, and gelatin. Network meta-analyses were conducted using random-effects model to calculate odds ratio (OR) and mean difference. Risk of Bias tool 2.0 was used to assess bias. Confidence in Network Meta-Analysis (CINeMA) web application was used to rate confidence in synthetic evidence. Results Fifty-eight trials ( n  = 26,351 patients) were identified. Seven fluid types were evaluated. Among patients with sepsis and surgery, balanced crystalloids and albumin achieved better survival, fewer acute kidney injury, and smaller blood transfusion volumes than saline and L-HES. In those with sepsis, balanced crystalloids significantly reduced mortality more than saline (OR 0.84; 95% CI 0.74–0.95) and L-HES (OR 0.81; 95% CI 0.69–0.95) and reduced acute kidney injury more than L-HES (OR 0.80; 95% CI 0.65–0.99). However, they required the greatest resuscitation volume among all fluid types, especially in trauma patients. In patients with traumatic brain injury, saline and L-HES achieved lower mortality than albumin and balanced crystalloids; especially saline was significantly superior to iso-oncotic albumin (OR 0.55; 95% CI 0.35–0.87). Conclusions Our network meta-analysis found that balanced crystalloids and albumin decreased mortality more than L-HES and saline in sepsis patients; however, saline or L-HES was better than iso-oncotic albumin or balanced crystalloids in traumatic brain injury patients. Trial registration PROSPERO website, registration number: CRD42018115641).

Spectral indices rarely show consistency in estimating crop traits across growth stages; thus, it is critical to simultaneously evaluate a group of spectral variables and select the most informative spectral indices for retrieving crop traits. The objective of this study was to explore the optimal spectral predictors for above-ground biomass (AGB) by applying Random Forest (RF) on three types of spectral predictors: the full spectrum, published spectral indices (Pub-SIs), and optimized spectral indices (Opt-SIs). Canopy hyperspectral reflectance of potato plants, treated with seven nitrogen (N) rates, was obtained during the tuber formation and tuber bulking from 2015 to 2016. Twelve Pub-SIs were selected, and their spectral bands were optimized using band optimization algorithms. Results showed that the Opt-SIs were the best input variables of RF models. Compared to the best empirical model based on Opt-SIs, the Opt-SIs based RF model improved the prediction of AGB, with R2 increased by 6%, 10%, and 16% at the tuber formation, tuber bulking, and for across the two growth stages, respectively. The Opt-SIs can significantly reduce the number of input variables. The optimized Blue nitrogen index (Opt-BNI) and Modified red-edge normalized difference vegetation index (Opt-mND705) combined with an RF model showed the best performance in estimating potato AGB at the tuber formation stage (R2 = 0.88). In the tuber bulking stage, only using optimized Nitrogen planar domain index (Opt-NPDI) as the input variable of the RF model produced satisfactory accuracy in training and testing datasets, with the R2, RMSE, and RE being 0.92, 208.6 kg/ha, and 10.3%, respectively. The Opt-BNI and Double-peak nitrogen index (Opt-NDDA) coupling with an RF model explained 86% of the variations in potato AGB, with the lowest RMSE (262.9 kg/ha) and RE (14.8%) across two growth stages. This study shows that combining the Opt-SIs and RF can greatly enhance the prediction accuracy for crop AGB while significantly reduces collinearity and redundancies of spectral data.

MicroRNAs (miRNAs) are emerging as a novel class of non-coding RNA molecules that regulate gene expression at a post-transcriptional level. More than 1000 miRNAs have been identified in human cells to date, and they are reported to play important roles in normal cell homeostasis, cell metastasis and disease pathogensis and progression. MiR-125, which is a highly conserved miRNA throughout diverse species from nematode to humans, consists of three homologs hsa-miR-125a, hsa-miR-125b-1 and hsa-miR-125-2. Members of this family have been validated to be down-regulated, exhibiting its disease-suppressing properties in many different types of diseases, while they also have disease-promoting functions in certain contexts. MiR-125 targets a number of genes such as transcription factors, matrix-metalloprotease, members of Bcl-2 family and others, aberrance of which may lead to abnormal proliferation, metastasis and invasion of cells, even carcinomas. Furthermore, miR-125 plays a crucial role in immunological host defense, especially in response to bacterial or viral infections. In this review, we summarize the implication of miR-125 family in disease suppression and promotion, focusing on carcinoma and host immune responses. We also discussed the potential of this miRNA family as promising biomarkers and therapeutic targets for different diseases in future.

High throughput field phenotyping techniques employing multispectral cameras allow extracting a variety of variables and features to predict yield and yield related traits, but little is known about which types of multispectral features are optimal to forecast yield potential in the early growth phase. In this study, we aim to identify multispectral features that are able to accurately predict yield and aid in variety classification at different growth stages throughout the season. Furthermore, we hypothesize that texture features (TFs) are more suitable for variety classification than for yield prediction. Throughout 2021 and 2022, a trial involving 19 and 18 European wheat varieties, respectively, was conducted. Multispectral images, encompassing visible, Red-edge, and near-infrared (NIR) bands, were captured at 19 and 22 time points from tillering to harvest using an unmanned aerial vehicle (UAV) in the first and second year of trial. Subsequently, orthomosaic images were generated, and various features were extracted, including single-band reflectances, vegetation indices (VI), and TFs derived from a gray level correlation matrix (GLCM). The performance of these features in predicting yield and classifying varieties at different growth stages was assessed using random forest models. Measurements during the flowering stage demonstrated superior performance for most features. Specifically, Red reflectance achieved a root mean square error (RMSE) of 52.4 g m -2 in the first year and 64.4 g m -2 in the second year. The NDRE VI yielded the most accurate predictions with an RMSE of 49.1 g m -2 and 60.6 g m -2 , respectively. Moreover, TFs such as CONTRAST and DISSIMILARITY displayed the best performance in predicting yield, with RMSE values of 55.5 g m -2 and 66.3 g m -2 across the two years of trial. Combining data from different dates enhanced yield prediction and stabilized predictions across dates. TFs exhibited high accuracy in classifying low and high-yielding varieties. The CORRELATION feature achieved an accuracy of 88% in the first year, while the HOMOGENEITY feature reached 92% accuracy in the second year. This study confirms the hypothesis that TFs are more suitable for variety classification than for yield prediction. The results underscore the potential of TFs derived from multispectral images in early yield prediction and varietal classification, offering insights for HTP and precision agriculture alike.

Axonal degeneration is central to clinical disability and disease progression in multiple sclerosis (MS). Myeloid cells such as brain-resident microglia and blood-borne monocytes are thought to be critically involved in this degenerative process. However, the exact underlying mechanisms have still not been clarified. We have previously demonstrated that human endogenous retrovirus type W (HERV-W) negatively affects oligodendroglial precursor cell (OPC) differentiation and remyelination via its envelope protein pathogenic HERV-W (pHERV-W) ENV (formerly MS-associated retrovirus [MSRV]-ENV). In this current study, we investigated whether pHERV-W ENV also plays a role in axonal injury in MS. We found that in MS lesions, pHERV-W ENV is present in myeloid cells associated with axons. Focusing on progressive disease stages, we could then demonstrate that pHERV-W ENV induces a degenerative phenotype in microglial cells, driving them toward a close spatial association with myelinated axons. Moreover, in pHERV-W ENV-stimulated myelinated cocultures, microglia were found to structurally damage myelinated axons. Taken together, our data suggest that pHERV-W ENV-mediated microglial polarization contributes to neurodegeneration in MS. Thus, this analysis provides a neurobiological rationale for a recently completed clinical study in MS patients showing that antibody-mediated neutralization of pHERV-W ENV exerts neuroprotective effects.

Stem cell activity is subject to non-cell-autonomous regulation from the local microenvironment, or niche. In adaption to varying physiological conditions and the ever-changing external environment, the stem cell niche has evolved with multifunctionality that enables stem cells to detect these changes and to communicate with remote cells/tissues to tailor their activity for organismal needs. The cyclic growth of hair follicles is powered by hair follicle stem cells (HFSCs). Using HFSCs as a model, we categorize niche cells into 3 functional modules, including signaling, sensing and message-relaying. Signaling modules, such as dermal papilla cells, immune cells and adipocytes, regulate HFSC activity through short-range cell-cell contact or paracrine effects. Macrophages capacitate the HFSC niche to sense tissue injury and mechanical cues and adipocytes seem to modulate HFSC activity in response to systemic nutritional states. Sympathetic nerves implement the message-relaying function by transmitting external light signals through an ipRGC-SCN-sympathetic circuit to facilitate hair regeneration. Hair growth can be disrupted by niche pathology, e.g. dysfunction of dermal papilla cells in androgenetic alopecia and influx of auto-reacting T cells in alopecia areata and lichen planopilaris. Understanding the functions and pathological changes of the HFSC niche can provide new insight for the treatment of hair loss.