Vitamin E and GPX4 cooperatively protect treg cells from ferroptosis and alleviate intestinal inflammatory damage in necrotizing enterocolitis.

BACKGROUND: The notable decline in the number of Tregs within Necrotizing enterocolitis (NEC) intestinal tissues，contribute to excessive inflammation and necrosis, yet the precise underlying factors remain enigmatic. Ferroptosis, a novel cell death stemming from a disrupted lipid redox metabolism, is the focus of this investigation. Specifically, this study delves into the ferroptosis of Treg cells in the context of NEC and observes the protective effects exerted by vitamin E intervention, which aims to mitigate ferroptosis of Treg cells. METHODS: To investigate the reduction of Treg cells in NEC intestine, we analyzed its association with ferroptosis from multiple angles. We constructed a mouse with a specific knockout of Gpx4 in Treg cells, aiming to examine the impact of Treg cell ferroptosis on NEC intestinal injury and localized inflammation. Ultimately, we employed vitamin E treatment to mitigate ferroptosis in NEC intestine's Treg cells, monitoring the subsequent amelioration in intestinal inflammatory damage. RESULTS: The diminution of Treg cells in NEC is attributed to ferroptosis stemming from diminished GPX4 expression. Gpx4-deficient Treg cells exhibit impaired immunosuppressive function and are susceptible to ferroptosis. This ferroptosis of Treg cells exacerbates intestinal damage and inflammatory response in NEC. Notably, Vitamin E can inhibit the ferroptosis of Treg cells, subsequently alleviating intestinal damage and inflammation in NEC. Additionally, Vitamin E bolsters the anti-lipid peroxidation capability of Treg cells by upregulating the expression of GPX4. CONCLUSION: In the context of NEC, the ferroptosis of Treg cells represents a significant factor contributing to intestinal tissue damage and an exaggerated inflammatory response. GPX4 is pivotal for the viability and functionality of Treg cells. Vitamin E exhibits the capability to mitigate the ferroptosis of Treg cells, thereby enhancing their number and function, which plays a crucial role in mitigating intestinal tissue damage and inflammatory response in NEC.

A radiomics nomogram based on multiparametric MRI for diagnosing focal cortical dysplasia and initially identifying laterality.

BACKGROUND: Focal cortical dysplasia (FCD) is the most common epileptogenic developmental malformation. The diagnosis of FCD is challenging. We generated a radiomics nomogram based on multiparametric magnetic resonance imaging (MRI) to diagnose FCD and identify laterality early. METHODS: Forty-three patients treated between July 2017 and May 2022 with histopathologically confirmed FCD were retrospectively enrolled. The contralateral unaffected hemispheres were included as the control group. Therefore, 86 ROIs were finally included. Using January 2021 as the time cutoff, those admitted after January 2021 were included in the hold-out set (n = 20). The remaining patients were separated randomly (8:2 ratio) into training (n = 55) and validation (n = 11) sets. All preoperative and postoperative MR images, including T1-weighted (T1w), T2-weighted (T2w), fluid-attenuated inversion recovery (FLAIR), and combined (T1w + T2w + FLAIR) images, were included. The least absolute shrinkage and selection operator (LASSO) was used to select features. Multivariable logistic regression analysis was used to develop the diagnosis model. The performance of the radiomic nomogram was evaluated with an area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration and clinical utility. RESULTS: The model-based radiomics features that were selected from combined sequences (T1w + T2w + FLAIR) had the highest performances in all models and showed better diagnostic performance than inexperienced radiologists in the training (AUCs: 0.847 VS. 0.664, p = 0.008), validation (AUC: 0.857 VS. 0.521, p = 0.155), and hold-out sets (AUCs: 0.828 VS. 0.571, p = 0.080). The positive values of NRI (0.402, 0.607, 0.424) and IDI (0.158, 0.264, 0.264) in the three sets indicated that the diagnostic performance of Model-Combined improved significantly. The radiomics nomogram fit well in calibration curves (p > 0.05), and decision curve analysis further confirmed the clinical usefulness of the nomogram. Additionally, the contrast (the radiomics feature) of the FCD lesions not only played a crucial role in the classifier but also had a significant correlation (r = -0.319, p < 0.05) with the duration of FCD. CONCLUSION: The radiomics nomogram generated by logistic regression model-based multiparametric MRI represents an important advancement in FCD diagnosis and treatment.

Phylotranscriptomic and ecological analyses reveal the evolution and morphological adaptation of Abies.

Coniferous forests are under severe threat of the rapid anthropogenic climate warming. Abies (firs), the fourth-largest conifer genus, is a keystone component of the boreal and temperate dark-coniferous forests and harbors a remarkably large number of relict taxa. However, the uncertainty of the phylogenetic and biogeographic history of Abies significantly impedes our prediction of future dynamics and efficient conservation of firs. In this study, using 1,533 nuclear genes generated from transcriptome sequencing and a complete sampling of all widely recognized species, we have successfully reconstructed a robust phylogeny of global firs, in which four clades are strongly supported and all intersectional relationships are resolved, although phylogenetic discordance caused mainly by incomplete lineage sorting and hybridization was detected. Molecular dating and ancestral area reconstruction suggest a Northern Hemisphere high-latitude origin of Abies during the Late Cretaceous, but all extant firs diversified during the Miocene to the Pleistocene, and multiple continental and intercontinental dispersals took place in response to the late Neogene climate cooling and orogenic movements. Notably, four critically endangered firs endemic to subtropical mountains of China, including A. beshanzuensis, A. ziyuanensis, A. fanjingshanensis and A. yuanbaoshanensis from east to west, have different origins and evolutionary histories. Moreover, three hotspots of species richness, including western North America, central Japan, and the Hengduan Mountains, were identified in Abies. Elevation and precipitation, particularly precipitation of the coldest quarter, are the most significant environmental factors driving the global distribution pattern of fir species diversity. Some morphological traits are evolutionarily constrained, and those linked to elevational variation (e.g., purple cone) and cold resistance (e.g., pubescent branch and resinous bud) may have contributed to the diversification of global firs. Our study sheds new light on the spatiotemporal evolution of global firs, which will be of great help to forest management and species conservation in a warming world.

Electrothermal-Assisted Photothermal Lubrication Surfaces for Continuous Anti-Icing/Deicing in Multiple Low-Temperature Environments.

Solving the problem of ice accumulation on solid surfaces is of great significance to the economic development of the country and the safety of people's lives. In this work, a coating with multifunctional photothermal/electrothermal solid-state lubrication (PEL) for anti-icing/deicing was prepared in layers based on the intrinsic properties of silicone oil and paraffin wax in combination with conductive graphite and multiwalled carbon nanotubes. Silicone oils and paraffins are used as lubricating media giving the coating excellent lubricity, which results in a water sliding angle (SA) of only 12° on the PEL surface. Meanwhile, PEL shows favorable static and dynamic ice resistance at low temperatures; at -10 °C, the freezing time of water droplets on the PEL surface is extended by at least 4 times compared to the bare substrate. Furthermore, PEL also offers highly efficient photothermal and electrothermal deicing performance, which can effectively remove the accumulated ice at a light intensity of 0.6 kW/m2 or an EPD of 0.1 W/cm2. Meanwhile, the synergistic deicing mechanism of photothermal and electrothermal was verified at -20 °C. Interestingly, the coating shows heat-assisted healing ability due to the phase change characteristic of paraffin wax, which allows the coating to regain lubricating properties after mechanical abrasion. Therefore, this work provides a reliable way for the design of stable all-weather anti-icing/deicing strategies at low temperatures.

Variations of silicon species, dissolution and crystallinity within sichars prepared under different heating rate.

Silicon within Si-rich biochars (sichar) plays a crucial role in immobilizing heavy metals and providing slow-releasing bioavailable silicon for silicophilic plants. However, the impact of heating rate on the silicon properties and carbon­silicon interactions in sichars remains unclear. In this study, rice husk was used as a silicon-rich biomass to prepare sichars at different heating rates (10, 30 and 60 °C per minute, and ultra-fast-pyrolysis), then experiments such as silicon concentration measurement, Raman and XRD characterization were conducted. The results showed that a faster heating rate reduced the carbon content during pyrolysis while promoted the formation of amorphous silica, resulting in a threefold increase in dissolved silicon in sichars prepared at 400 °C. Additionally, we observed the formation of a meta-stable SiO2 polymorph (tridymite) in rice husk-derived biochars under fast heating, differing from the previously observed quartz generated at slow heating rates. Regarding the CSi relationship, a faster heating rate facilitated the removal of the surface carbon layer, exposing the underlying silicon layer. This led to more soluble silicon species and less encapsulated silicon, resulting in a continuous release and cumulative silicon dissolution amount 1.2 times and 1.6-1.9 times higher, respectively, than those in slow heating rate-derived sichars. Consequently, this enhanced silicon uptake in rice seedlings. Our findings indicate that beyond pyrolysis temperature, the heating rate significantly affects the silicon species, silicon dissolution behavior, and carbon­silicon relationships of biochar, ultimately determines the properties and applications of sichars.

Enhancing the Efficiency and Stability of Perovskite Solar Cells Using Chemical Bath Deposition of SnO2 Electron Transport Layers and 3D/2D Heterojunctions.

Chemical bath deposition (CBD) is an effective technique used to produce high-quality SnO2 electron transport layers (ETLs) employed in perovskite solar cells (PSCs). By optimizing the CBD process, high-quality SnO2 films are obtained with minimal oxygen vacancies and close energy level alignment with the perovskite layer. In addition, the 3D perovskite layers are passivated with n-butylammonium iodide (BAI), iso-pentylammonium iodide (PNAI), or 2-methoxyethylammonium iodide (MOAI) to form 3D/2D heterojunctions, resulting in defect passivation, suppressing ion migration and improving charge carrier extraction. As a result of these heterojunctions, the power conversion efficiency (PCE) of the PSCs increased from 21.39% for the reference device to 23.70% for the device containing the MOAI-passivated film. The 2D perovskite layer also provides a hydrophobic barrier, thus enhancing stability to humidity. Notably, the PNAI-based device exhibited remarkable stability, retaining approximately 95% of its initial efficiency after undergoing 1000-h testing in an N2 environment at room temperature.

Hot Hearts on Bone Scintigraphy Are Not All Amyloidosis: Hyperoxaluria-Associated Cardiomyopathy.

ABSTRACT: A 54-year-old woman with a history of end-stage renal disease was found to have infiltrative cardiomyopathy by echocardiography. 99mTc-pyrophosphate (99mTc-PYP) scintigraphy was positive with a remarkable myocardial uptake. Gene test found a mutation of AGXT, confirming a final diagnosis of primary hyperoxaluria. Radiotracer uptake was due to high myocardial oxalate deposition. This case illustrates false positivity of the 99mTc-PYP scan caused by hyperoxaluria-associated cardiomyopathy, which raises awareness for other conditions apart from amyloid cardiomyopathy.

Unraveling the impact of irritability on esophageal diseases: Insights from multivariable Mendelian randomization analysis.

BACKGROUND: Previous studies have suggested a potential association between irritability and the risk of various diseases. However, establishing a causal relationship has remained a significant challenge. To address this issue, we employed Mendelian randomization (MR), a sophisticated approach that leverages genotype data to emulate the conditions of randomized controlled trials. This method enables us to investigate the potential causal link between irritability and the susceptibility to esophageal diseases. METHODS: We conducted an extensive multivariable MR analysis using summary-level data from genome-wide association studies (GWAS) encompassing various esophageal diseases, including gastroesophageal reflux disease (GERD), esophageal cancer (EC), and Barrett's esophagus. Both univariable and multivariable MR analyses were performed to elucidate and confirm the causal association between genetically predicted irritability and the incidence of esophageal diseases. RESULTS: Based on our primary causal effects model utilizing MR analyses with the inverse-variance weighted (IVW) method, genetically predicted irritability was identified as a risk factor for GERD (OR = 2.413; 95 % CI: 1.678-3.470; P = 2.03E-06) and Barrett's esophagus (OR = 2.306; 95 % CI: 1.042-5.101; P = 0.039). However, irritability was not found to be associated with the risk of EC, even after adjusting for BMI, smoking initiation, and alcohol consumption. CONCLUSION: The multivariable MR analysis performed in this study demonstrated a causal relationship between irritability and esophageal diseases. It is imperative to acknowledge the need for further large-scale prospective studies to validate these findings.

The construction of a maize-teosinte introgression population and quantitative trait loci analysis of their 21 agronomic traits.

Teosinte is a progenitor species of maize (Zea mays ssp. mays) that retains a significant reservoir of genetic resources unaltered via the domestication process. To harness and explore the genetic reservoirs inherent in teosinte, we used the cultivated publicly inbred line H95 and wild species PI566673 (Zea mays ssp. mexicana) to develop a set of introgression lines (ILs), including 366 BC2F5 lines. Using these lines, 12481 high-quality polymorphic homozygous single nucleotide polymorphisms were converted into 2358 bin markers based on Genotyping by Target Sequencing technology. The homozygous introgression ratio in the ILs was approximately 12.1 % and the heterozygous introgression ratio was approximately 5.7 %. Based on the population phenotypic data across 21 important agronomic traits collected in Sanya and Beijing, 185 and 156 quantitative trait loci (QTLs) were detected in Sanya and Beijing, respectively, with 64 stable QTLs detected in both locations. We detected 12 QTL clusters spanning 10 chromosomes consisting of diverse QTLs related to yield traits such as grain size and weight. In addition, we identified useful materials in the ILs for further gene cloning of related variations. For example, some heterogeneous inbred families with superior genetic purity, shorter target heterozygotes, and some ILs exhibit clear morphological variation associated with plant growth, development, and domestication, manifesting traits such as white stalks, sharp seeds, and cob shattering. In conclusion, our results provide a robust foundation for delving into the genetic reservoirs of teosinte, presenting a wealth of genetic resources and offering insight into the genetic architecture underlying maize agronomic traits.

Electrified Operando-Freezing of Electrocatalytic CO2 Reduction Cells for Cryogenic Electron Microscopy.

The ability to freeze and stabilize reaction intermediates in their metastable states and obtain their structural and chemical information with high spatial resolution is critical to advance materials technologies such as catalysis and batteries. Here, we develop an electrified operando-freezing methodology to preserve these metastable states under electrochemical reaction conditions for cryogenic electron microscopy (cryo-EM) imaging and spectroscopy. Using Cu catalysts for CO2 reduction as a model system, we observe restructuring of the Cu catalyst in a CO2 atmosphere while the same catalyst remains intact in air at the nanometer scale. Furthermore, we discover the existence of a single valence Cu (1+) state and C-O bonding at the electrified liquid-solid interface of the operando-frozen samples, which are key reaction intermediates that traditional ex situ measurements fail to detect. This work highlights our novel technique to study the local structure and chemistry of electrified liquid-solid interfaces, with broad impact beyond catalysis.

Cortical microstructural abnormalities in amyotrophic lateral sclerosis: a gray matter-based spatial statistics study.

Background: Amyotrophic lateral sclerosis (ALS)-related white-matter microstructural abnormalities have received considerable attention; however, gray-matter structural abnormalities have not been fully elucidated. This study aimed to evaluate cortical microstructural abnormalities in ALS and determine their association with disease severity. Methods: This study included 34 patients with ALS and 30 healthy controls. Diffusion-weighted data were used to estimate neurite orientation dispersion and density imaging (NODDI) parameters, including neurite density index (NDI) and orientation dispersion index (ODI). We performed gray matter-based spatial statistics (GBSS) in a voxel-wise manner to determine the cortical microstructure difference. We used the revised ALS Functional Rating Scale (ALSFRS-R) to assess disease severity and conducted a correlation analysis between NODDI parameters and ALSFRS-R. Results: In patients with ALS, the NDI reduction involved several cortical regions [primarily the precentral gyrus, postcentral gyrus, temporal cortex, prefrontal cortex, occipital cortex, and posterior parietal cortex; family-wise error (FWE)-corrected P<0.05]. ODI decreased in relatively few cortical regions (including the precentral gyrus, postcentral gyrus, prefrontal cortex, and inferior parietal lobule; FWE-corrected P<0.05). The NDI value in the left precentral and postcentral gyrus was positively correlated with the ALS disease severity (FWE-corrected P<0.05). Conclusions: The decreases in NDI and ODI involved both motor-related and extra-motor regions and indicated the presence of gray-matter microstructural impairment in ALS. NODDI parameters are potential imaging biomarkers for evaluating disease severity in vivo. Our results showed that GBSS is a feasible method for identifying abnormalities in the cortical microstructure of patients with ALS.

The prognostic value of controlling nutritional status score on esophageal squamous cell carcinoma patients with neoadjuvant therapy followed by esophagectomy-a retrospective research.

Background: A variety of nutritional evaluation parameters has been documented as prognostic indicators in some malignancies. However, the prognostic significance of the controlling nutritional status (CONUT) score, as one of these nutritional indices, in patients with esophageal squamous cell carcinoma (ESCC) remains unclear and warrants investigation. Our study sought to elucidate the prognostic value of this nutritional index in ESCC patients who underwent neoadjuvant therapy followed by esophagectomy. Methods: This retrospective study encompassed 314 patients diagnosed with ESCC who underwent neoadjuvant therapy followed by esophagectomy at West China Hospital of Sichuan University between August 2016 and August 2021. CONUT scores were computed at two specific time points: prior to neoadjuvant therapy initiation and before surgery, utilizing serum albumin, total lymphocyte, and cholesterol levels of ESCC patients. Furthermore, the delta CONUT (ΔCONUT) score was derived by subtracting the preoperative CONUT score from the pretreatment CONUT score. The associations between CONUT scores and various survival outcomes were evaluated using Kaplan-Meier methods and Cox regression analysis. Results: Patients with a high preoperative CONUT score demonstrated a higher postoperative complication rate [odds ratio (OR) =2.009, 95% confidence interval (CI): 1.150-3.510, P=0.01] compared to those in the low CONUT group. Multivariate analysis revealed that a ΔCONUT score ≥0 served as an independent negative prognostic indicator for increased postoperative complications (OR =3.008, 95% CI: 1.509-5.999, P=0.002) and poorer overall survival [hazard ratio (HR) =2.388, 95% CI: 1.052-5.422, P=0.04] in ESCC patients who underwent neoadjuvant therapy combined with esophagectomy. Conclusions: A high preoperative CONUT score and a ΔCONUT score ≥0 were indicative of a poor prognostic nutritional status in ESCC patients who had undergone neoadjuvant therapy followed by esophagectomy.

MFGE8 promotes adult hippocampal neurogenesis in rats following experimental subarachnoid hemorrhage via modifying the integrin ß3/Akt signaling pathway.

Subarachnoid hemorrhage (SAH) is one of the most severe type of cerebral strokes, which can cause multiple cellular changes in the brain leading to neuronal injury and neurological deficits. Specifically, SAH can impair adult neurogenesis in the hippocampal dentate gyrus, thus may affecting poststroke neurological and cognitive recovery. Here, we identified a non-canonical role of milk fat globule epidermal growth factor 8 (MFGE8) in rat brain after experimental SAH, involving a stimulation on adult hippocampal neurogenesis(AHN). Experimental SAH was induced in Sprague-Dawley rats via endovascular perforation, with the in vivo effect of MFGE8 evaluated via the application of recombinant human MFGE8 (rhMFGE8) along with pharmacological interventions, as determined by hemorrhagic grading, neurobehavioral test, and histological and biochemical analyses of neurogenesis related markers. Results: Levels of the endogenous hippocampal MFGE8 protein, integrin-ß3 and protein kinase B (p-Akt) were elevated in the SAH relative to control groups, while that of hippocalcin (HPCA) and cyclin D1 showed the opposite change. Intraventricular rhMGFE8 infusion reversed the decrease in doublecortin (DCX) immature neurons in the DG after SAH, along with improved the short/long term neurobehavioral scores. rhMGFE8 treatment elevated the levels of phosphatidylinositol 3-kinase (PI3K), p-Akt, mammalian target of rapamycin (mTOR), CyclinD1, HPCA and DCX in hippocampal lysates, but not that of integrin ß3 and Akt, at 24 hr after SAH. Treatment of integrin ß3 siRNA, the PI3K selective inhibitor ly294002 or Akt selective inhibitor MK2206 abolished the effects of rhMGFE8 after SAH. In conclusion, MFGE8 is upregulated in the hippocampus in adult rats with reduced granule cell genesis. rhMFGE8 administration can rescue this impaired adult neurogenesis and improve neurobehavioral recovery. Mechanistically, the effect of MFGE8 on hippocampal adult neurogenesis is mediated by the activation of integrin ß3/Akt pathway. These findings suggest that exogenous MFGE8 may be of potential therapeutic value in SAH management. Graphical abstract and proposed pathway of rhMFGE8 administration attenuate hippocampal injury by improving neurogenesis in SAH models. SAH caused hippocampal injury and neurogenesis interruption. Administered exogenous MFGE8, recombinant human MFGE8(rhMFGE8), could ameliorate hippocampal injury and improve neurological functions after SAH. Mechanistically, MFGE8 bind to the receptor integrin ß3, which activated the PI3K/Akt pathway to increase the mTOR expression, and further promote the expression of cyclin D1, HPCA and DCX. rhMFGE8 could attenuated hippocampal injury by improving neurogenesis after SAH, however, know down integrin ß3 or pharmacological inhibited PI3K/Akt by ly294002 or MK2206 reversed the neuro-protective effect of rhMFGE8.

Preparation of hydroxyapatite and its elimination of excess fluoride from aqueous solution.

Excess fluoride in aqueous solutions can significantly affect dental and bone health. This study used two methods to prepare hydroxyapatite to remove fluoride ions from water. The experiments showed that the adsorption capacity and removal rate of hydroxyapatite (Xq-HAP) prepared by the novel method were higher than for the hydroxyapatite (Yt-HAP) prepared by the conventional method. The maximum fluoride ion trapping capacity of Xq-HAP could reach 29.04 mg g-1 under the conditions of pH = 5 and an F ion concentration of 10 mg L-1. The materials were characterized by SEM, XRD, BET, XPS, and FTIR. An investigation was conducted to examine the impact of contact time, adsorbent dosage, fluoride concentration, solution pH, temperature, and several other parameters on the removal of fluoride. Adsorption equilibrium was reached in approximately 3 h at an initial fluoride concentration of 10 mg L-1. It can be seen that the adsorbent has a faster ability to trap fluoride ions. The adsorption kinetics and Langmuir isotherm indicated that fluoride ion adsorption is a monolayer chemisorption process. Further characterization and kinetic studies indicated that the removal mechanism involves ion exchange, electrostatic interactions, and complexation. After five adsorption cycles, the adsorption capacity reaches 23 mg g-1.

High-sensitive sensory neurons exacerbate rosacea-like dermatitis in mice by activating γδ T cells directly.

Rosacea patients show facial hypersensitivity to stimulus factors (such as heat and capsaicin); however, the underlying mechanism of this hyperresponsiveness remains poorly defined. Here, we show capsaicin stimulation in mice induces exacerbated rosacea-like dermatitis but has no apparent effect on normal skin. Nociceptor ablation substantially reduces the hyperresponsiveness of rosacea-like dermatitis. Subsequently, we find that γδ T cells express Ramp1, the receptor of the neuropeptide CGRP, and are in close contact with these nociceptors in the skin. γδ T cells are significantly increased in rosacea skin lesions and can be further recruited and activated by neuron-secreted CGRP. Rosacea-like dermatitis is reduced in T cell receptor δ-deficient (Tcrd-/-) mice, and the nociceptor-mediated aggravation of rosacea-like dermatitis is also reduced in these mice. In vitro experiments show that CGRP induces IL17A secretion from γδ T cells by regulating inflammation-related and metabolism-related pathways. Finally, rimegepant, a CGRP receptor antagonist, shows efficacy in the treatment of rosacea-like dermatitis. In conclusion, our findings demonstrate a neuron-CGRP-γδT cell axis that contributes to the hyperresponsiveness of rosacea, thereby showing that targeting CGRP is a potentially effective therapeutic strategy for rosacea.

Effects of respiratory muscle training on post-stroke rehabilitation: A systematic review and meta-analysis.

BACKGROUND: Stroke often results in significant respiratory dysfunction in patients. Respiratory muscle training (RMT) has been proposed as a rehabilitative intervention to address these challenges, but its effectiveness compared to routine training remains debated. This systematic review and meta-analysis aim to evaluate the effects of RMT on exercise tolerance, muscle strength, and pulmonary function in post-stroke patients. AIM: To systematically assess the efficacy of RMT in improving exercise tolerance, respiratory muscle strength, and pulmonary function in patients recovering from a stroke, and to evaluate whether RMT offers a significant advantage over routine training modalities in enhancing these critical health outcomes in the post-stroke population. METHODS: Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, a comprehensive search across PubMed, Embase, Web of Science, and the Cochrane Library was conducted on October 19, 2023, without temporal restrictions. Studies were selected based on the predefined inclusion and exclusion criteria focusing on various forms of RMT, control groups, and outcome measures [including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), maximal voluntary ventilation (MVV), peak expiratory flow (PEF), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and 6-min walking test (6MWT)]. Only randomized controlled trials (RCTs) were included. Data extraction and quality assessment were conducted independently by two reviewers using the Cochrane Collaboration's risk of bias tool. Statistical analyses, including those using the fixed-effect and random-effects models, sensitivity analysis, and publication bias assessment, were performed using Review Manager software. RESULTS: A total of 15 RCTs were included. Results indicated significant improvements in MIP (12.51 cmH2O increase), MEP (6.24 cmH2O increase), and various pulmonary function parameters (including FEV1, FVC, MVV, and PEF). A substantial increase in 6MWT distance (22.26 meters) was also noted. However, the heterogeneity among studies was variable, and no significant publication bias was detected. CONCLUSION: RMT significantly enhances walking ability, respiratory muscle strength (MIP and MEP), and key pulmonary function parameters (FEV1, FVC, MVV, and PEF) in post-stroke patients. These findings support the incorporation of RMT into post-stroke rehabilitative protocols.

Screening of [18F]Florbetazine for Aß Plaques and a Head-to-Head Comparison Study with [11C]Pittsburgh Compound-B ([11C]PiB) in Human Subjects.

Positron emission tomography (PET) imaging of amyloid-ß (Aß) has emerged as a crucial strategy for early diagnosis and monitoring of therapeutic advancements targeting Aß. In our previous first-in-human study, we identified that [18F]Florbetazine ([18F]92), featuring a diaryl-azine scaffold, exhibits higher cortical uptake in Alzheimer's disease (AD) patients compared to healthy controls (HC). Building upon these promising findings, this study aimed to characterize the diagnostic potential of [18F]92 and its dimethylamino-modified tracer [18F]91 and further compare them with the benchmark [11C]PiB in the same cohort of AD patients and age-matched HC subjects. The cortical accumulation of these tracers was evident, with no significant radioactivity retention observed in the cortex of HC subjects, consistent with [11C]PiB images (correlation coefficient of 0.9125 and 0.7883 between [18F]Florbetazine/[18F]91 and [11C]PiB, respectively). Additionally, quantified data revealed higher standardized uptake value ratios (SUVR) (with the cerebellum as the reference region) of [18F]Florbetazine/[18F]91 in AD patients compared to the HC group ([18F]Florbetazine: 1.49 vs 1.16; [18F]91: 1.33 vs 1.20). Notably, [18F]Florbetazine exhibited less nonspecific bindings in myelin-rich regions, compared to the dimethylamino-substituted [18F]91, akin to [11C]PiB. Overall, this study suggests that [18F]Florbetazine displays superior characteristics to [18F]91 in identifying Aß pathology in AD. Furthermore, the close agreement between the uptakes in nontarget regions for [18F]Florbetazine and [11C]PiB in this head-to-head comparison study underscores its suitability for both clinical and research applications.

The long non-coding RNA CCAT1 promotes erlotinib resistance in cholangiocarcinoma by inducing epithelial-mesenchymal transition via the miR-181a-5p/ROCK2 axis.

Cholangiocarcinoma (CCA) is a common malignancy of the digestive system, and its treatment is greatly challenged by rising chemoresistance. Long non-coding RNAs (lncRNAs) have been shown to play critical roles in the development of drug resistance in tumors. However, the role of the lncRNA CCAT1 in erlotinib resistance in CCA remains unclear. In this investigation, we identified CCAT1 as a pivotal factor contributing to erlotinib resistance in CCA. Furthermore, we uncovered that lncRNA CCAT1 modulated epithelial-mesenchymal transition (EMT) through Rho-associated coiled-coil-forming protein kinase 2 (ROCK2), thereby conferring erlotinib resistance upon CCA cells. Mechanistically, we demonstrated that miR-181a-5p interacted with CCAT1 to modulate the expression of ROCK2. Collectively, these findings shed light on the significant role of CCAT1 in the development of erlotinib resistance in CCA. The functional suppression of CCAT1 holds promise in enhancing the sensitivity to erlotinib by reversing EMT through the miR-181a-5p/ROCK2 signaling pathway. These findings provide valuable insights into the mechanisms underlying erlotinib resistance in CCA and the potential strategies for its treatment.

Type III adenylyl cyclase is essential for follicular development in female mice and their reproductive lifespan.

Premature ovarian failure (POF) is a complex and heterogeneous disease that causes infertility and subfertility. However, the molecular mechanism of POF has not been fully elucidated. Here, we show that the loss of adenylyl cyclase III (Adcy3) in female mice leads to POF and a shortened reproductive lifespan. We found that Adcy3 is abundantly expressed in mouse oocytes. Adcy3 knockout mice exhibited the excessive activation of primordial follicles, progressive follicle loss, follicular atresia, and ultimately POF. Mechanistically, we found that mitochondrial oxidative stress in oocytes significantly increased with age in Adcy3-deficient mice and was accompanied by oocyte apoptosis and defective folliculogenesis. In contrast, compared with wild-type female mice, humanized ADCY3 knock-in female mice exhibited improved fertility with age. Collectively, these results reveal that the previously unrecognized Adcy3 signaling pathway is tightly linked to female ovarian aging, providing potential pharmaceutical targets for preventing and treating POF.

Clinical efficacy of different therapeutic strategies in patients with spontaneous rupture of the esophagus: a multicenter retrospective cohort study.

BACKGROUND: The therapeutic strategy for patients with spontaneous rupture of the esophagus includes surgical repair, endoscopic therapy, supportive care, and others. However, no evidence exists to direct clinical decision-making regarding the choice of operative and nonoperative management. The aim of this study was to determine the clinical efficacy of different therapeutic strategies in both general and stratified patients. METHODS: This study retrospectively analyzed a consecutive cohort of 101 patients at nine tertiary referral hospital centers in China. Patients were divided into operative and nonoperative groups based on the initial treatment. Short-term outcomes, including 90-day mortality, length of hospital stay, and postoperative leakage were compared. Subgroup analysis was performed based on treatment timing and Pittsburgh perforation severity score (PSS). RESULTS: Of 101 patients, 60 (58.4%) underwent operative management. A significant difference of 90-day mortality between operative and nonoperative groups was observed (15.0% vs. 34.1%, P=0.031). Operative management tend to yield similar therapeutic benefits in timely (OR, 0.250; 95% CI, 0.05-1.14, P=0.073) and delayed (OR, 0.42; 95% CI, 0.12-1.47, P=0.175) treatment groups. Based on PSS stratification, operative management significantly decreased the risk of 90-day mortality (OR, 0.211; 95% CI, 0.064-0.701; P=0.011) for patients in low- and moderate-risk groups but may be detrimental for patients in high-risk group (OR, 1.333; 95% CI, 0.233-7.626; P=0.746). CONCLUSIONS: Operative management might be superior to nonoperative management for low- and moderate-risk patients with spontaneous rupture of the esophagus. However, for patients at high risks, operative management might not provide additional benefits compared with nonoperative management. Further research involving larger sample sizes is required for accurate patient stratification and conclusive evidence-based guideline.