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Macrocyclic conformations play a crucial role in regulating their properties. Our understanding of the determinants to control macrocyclic conformation interconversion is still in its infancy. Here we present a macrocycle, octamethyl cyclo[4](1,3-(4,6)-dimethylbenzene)[4]((4,6-benzene)(1,3-dicarboxylate) (OC-4), that can exist at 298 K as two stable atropisomers with C2v and C4v symmetry denoted as C2v-OC-4 and C4v-OC-4, respectively. Heating induces the efficient stepwise conversion of C2v- to C4v-OC-4 via a Cs-symmetric intermediate (Cs-OC-4). It differs from the typical transition state-mediated processes of simple C–C single bond rotations. Hydrolysis and further esterification with a countercation dependence promote the generation of C2v- and Cs-OC-4 from C4v-OC-4. In contrast to C2v-OC-4, C4v-OC-4 can bind linear guests to form pseudo-rotaxans, or bind C60 or C70 efficiently. The present study highlights the differences in recognition behavior that can result from conformational interconversion, as well as providing insights into the basic parameters that govern coupled molecular rotations. The three-dimensional conformation of macrocycles determine their chemical and recognition properties and the factors that influence the interconversion between macrocyclic forms are poorly understood. Here the authors describe a macrocycle existing as two stable atropisomers and the mechanism behind the thermally-induced transition between them. [ABSTRACT FROM AUTHOR]

This study elucidates the molecular mechanisms by which FABP3 regulates neuronal apoptosis via mitochondrial autophagy in the context of cerebral ischemia-reperfusion (I/R). Employing a transient mouse model of middle cerebral artery occlusion (MCAO) established using the filament method, brain tissue samples were procured from I/R mice. High-throughput transcriptome sequencing on the Illumina CN500 platform was performed to identify differentially expressed mRNAs. Critical genes were selected by intersecting I/R-related genes from the GeneCards database with the differentially expressed mRNAs. The in vivo mechanism was explored by infecting I/R mice with lentivirus. Brain tissue injury, infarct volume ratio in the ischemic penumbra, neurologic deficits, behavioral abilities, neuronal apoptosis, apoptotic factors, inflammatory factors, and lipid peroxidation markers were assessed using H&E staining, TTC staining, Longa scoring, rotation experiments, immunofluorescence staining, and Western blot. For in vitro validation, an OGD/R model was established using primary neuron cells. Cell viability, apoptosis rate, mitochondrial oxidative stress, morphology, autophagosome formation, membrane potential, LC3 protein levels, and colocalization of autophagosomes and mitochondria were evaluated using MTT assay, LDH release assay, flow cytometry, ROS/MDA/GSH-Px measurement, transmission electron microscopy, MitoTracker staining, JC-1 method, Western blot, and immunofluorescence staining. FABP3 was identified as a critical gene in I/R through integrated transcriptome sequencing and bioinformatics analysis. In vivo experiments revealed that FABP3 silencing mitigated brain tissue damage, reduced infarct volume ratio, improved neurologic deficits, restored behavioral abilities, and attenuated neuronal apoptosis, inflammation, and mitochondrial oxidative stress in I/R mice. In vitro experiments demonstrated that FABP3 silencing restored OGD/R cell viability, reduced neuronal apoptosis, and decreased mitochondrial oxidative stress. Moreover, FABP3 induced mitochondrial autophagy through ROS, which was inhibited by the free radical scavenger NAC. Blocking mitochondrial autophagy with sh-ATG5 lentivirus confirmed that FABP3 induces mitochondrial dysfunction and neuronal apoptosis by activating mitochondrial autophagy. In conclusion, FABP3 activates mitochondrial autophagy through ROS, leading to mitochondrial dysfunction and neuronal apoptosis, thereby promoting cerebral ischemia-reperfusion injury. [ABSTRACT FROM AUTHOR]

Celiac disease (CD), triggered by exposure to gluten in genetically susceptible individuals, is an immune-mediated small bowel disease affecting about 1% of the population worldwide. But the prevalence of CD varies with age, sex, and location. A strict gluten-free diet remains the primary treatment for CD, currently. Most of patients with CD respond well to gluten-free diet with good prognosis, while some patients fail to get symptomatic relief or histological remission (e.g., nonresponsive or refractory CD). Because of heterogeneous clinical appearance, the diagnosis of CD is difficult. Moreover, malignant complications and poor outcomes accompanied with refractory CD present great challenges in disease management. Over the past three decades, cross-sectional imaging techniques (computed tomography [CT] and magnetic resonance imaging [MRI]) play an important role in small bowel inflammatory and neoplastic diseases. Compared with endoscopic techniques, cross-sectional imaging permits clearly presentation of both intraluminal and extraluminal abnormalities. It provides vascular and functional information, thus improving the possibility as diagnostic and follow-up tool. The value of cross-sectional imaging for patients with suspected or confirmed CD has been gradually demonstrated. Studies revealed that certain features suggested by cross-sectional imaging could help to establish the early diagnosis of CD. Besides, the potential contributions of cross-sectional imaging may lie in the evaluation of disease activity and severity, which helps guiding management strategies. The purpose of this review is to provide current overviews and future directions of cross-sectional imaging in adult CD, thus facilitating the understanding and application in clinical practice. Clinical relevance statement: In this review, we systematically summarized the existing knowledge of cross-sectional imaging in adult CD and analyzed their possible roles in clinical practice, including disease diagnosis, complication identification, treatment evaluation, and prognostic prediction. Key Points: • Regarding a condition described as "celiac iceberg", celiac disease remains underdiagnosed and undertreated. • Cross-sectional imaging is helpful in clinical management of celiac disease, including disease diagnosis, complication identification, treatment evaluation, and prognostic prediction. • Cross-sectional imaging should be considered as the valuable examination in patients suspected from celiac disease. [ABSTRACT FROM AUTHOR]

Early and accurate diagnosis of ear deformities in newborns is crucial for an effective non-surgical correction treatment, since this commonly seen ear anomalies would affect aesthetics and cause mental problems if untreated. It is not easy even for experienced physicians to diagnose the auricular deformities of newborns and the classification of the sub-types, because of the rich bio-metric features embedded in the ear shape. Machine learning has already been introduced to analyze the auricular shape. However, there is little publicly available datasets of ear images from newborns. We released a dataset that contains quality-controlled photos of 3,852 ears from 1,926 newborns. The dataset also contains medical diagnosis of the ear shape, and the health data of each newborn and its mother. Our aim is to provide a freely accessible dataset, which would facilitate researches related with ear anatomies, such as the AI-aided detection and classification of auricular deformities and medical risk analysis. [ABSTRACT FROM AUTHOR]

Chronic pain causes both physical suffering and comorbid mental symptoms such as anhedonia. However, the neural circuits and molecular mechanisms underlying these maladaptive behaviors remain elusive. Here using a mouse model, we report a pathway from vesicular glutamate transporter 3 neurons in the dorsal raphe nucleus to dopamine neurons in the ventral tegmental area (VGluT3DRN→DAVTA) wherein population-level activity in response to innocuous mechanical stimuli and sucrose consumption is inhibited by chronic neuropathic pain. Mechanistically, neuropathic pain dampens VGluT3DRN → DAVTA glutamatergic transmission and DAVTA neural excitability. VGluT3DRN → DAVTA activation alleviates neuropathic pain and comorbid anhedonia-like behavior (CAB) by releasing glutamate, which subsequently promotes DA release in the nucleus accumbens medial shell (NAcMed) and produces analgesic and anti-anhedonia effects via D2 and D1 receptors, respectively. In addition, VGluT3DRN → DAVTA inhibition produces pain-like reflexive hypersensitivity and anhedonia-like behavior in intact mice. These findings reveal a crucial role for VGluT3DRN → DAVTA → D2/D1NAcMed pathway in establishing and modulating chronic pain and CAB. The neural circuit mechanisms underlying chronic pain and comorbid anhedonia remain poorly understood. Here, the authors show the critical role of the DRN–VTA–NAcMed pathway in establishing and modulating chronic neuropathic pain and comorbid anhedonia. [ABSTRACT FROM AUTHOR]

Background and objective: Acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS) was increasingly recognized as one of the most severe acute hyperimmune response of coronavirus disease 2019 (COVID-19). Clofazimine (CFZ) has attracted attention due to its anti-inflammatory property in immune diseases as well as infectious diseases. However, the role and potential molecular mechanism of CFZ in anti-inflammatory responses remain unclear. Methods: We analyze the protein expression profiles of CFZ and LPS from Raw264.7 macrophages using quantitative proteomics. Next, the protective effect of CFZ on LPS-induced inflammatory model is assessed, and its underlying mechanism is validated by molecular biology analysis. Results: LC–MS/MS-based shotgun proteomics analysis identified 4746 (LPS) and 4766 (CFZ) proteins with quantitative information. The key proteins and their critical signal transduction pathways including TLR4/NF-κB/HIF-1α signaling was highlighted, which was involved in multiple inflammatory processes. A further analysis of molecular biology revealed that CFZ could significantly inhibit the proliferation of Raw264.7 macrophages, decrease the levels of TNF-α and IL-1β, alleviate lung histological changes and pulmonary edema, improve the survival rate, and down-regulate TLR4/NF-κB/HIF-1α signaling in LPS model. Conclusion: This study can provide significant insight into the proteomics-guided pharmacological mechanism study of CFZ and suggest potential therapeutic strategies for infectious disease. [ABSTRACT FROM AUTHOR]

Pain is a common symptom of an illness. For decades, pain treatments such as non-steroidal anti-inflammatory drugs, opioids, and surgical nerve blocking have been widely used, but each method has its limitations. Photobiomodulation is a recently developed method for pain management, with light-emitting diodes (LEDs) being a more recent development used in pain management because of their low cost, low side effects, and high safety. Here, we reviewed the phototherapeutic effects of LEDs on different pain conditions. We also discussed possible physicochemical and neurobiological mechanisms underlying LED therapy, especially its effects on inflammatory pain. [ABSTRACT FROM AUTHOR]

Precipitation in the equatorial African rainforest plays an important role in both the regional hydrological cycle and the global climate variability. Previous studies mostly focus on the trends of drought in recent decades or long-time scales. Using two observational datasets, we reveal a remarkable weakening of the seasonal precipitation cycle over this region from 1979 to 2015, with precipitation significantly increased in the boreal winter dry season (~ 0.13 mm/day/decade) and decreased in the boreal spring wet season (~ 0.21 mm/day/decade), which account for ~ 14% (the precipitation changes from 1979 to 2015) of their respective climatological means. We further use a state-of-the-art atmospheric model to isolate the impact of sea surface temperature change from different ocean basins on the precipitation changes in the dry and wet seasons. Results show that the strengthening precipitation in the dry season is mainly driven by the Atlantic warming, whereas the weakening precipitation in the wet season can be primarily attributed to the Indian Ocean. Warming Atlantic intensifies the zonal circulation over the African rainforest, strengthening moisture convergence and intensifying precipitation in the boreal winter dry season. Warming Indian Ocean contributes more to reducing the zonal circulation and suppressing the convection in the boreal spring wet season, leading to an opposite effect on precipitation. This result has important implication on local ecology as well as global climate system. [ABSTRACT FROM AUTHOR]

The Pacific Walker circulation (WC) is a major component of the global climate system. It connects the Pacific sea surface temperature (SST) variability to the climate variabilities from the other ocean basins to the mid- and high latitudes. Previous studies indicated that the ENSO-related atmospheric feedback, in particular, the surface wind response is largely underestimated in AMIP and CMIP models. In this study, we further investigate the responses in the WC stream function and the sea level pressure (SLP) to the ENSO-related SST variability by comparing the responses in 45 AMIP and 63 CMIP models and six reanalysis datasets. We reveal a diversity in the performances of simulated SLP and WC between different models. While the SLP responses to the El Niño-related SST variability are well simulated in most of the atmospheric and coupled models, the WC stream function responses are largely underestimated in most of these models. The WC responses in the AMIP5/6 models capture ~ 75% of those in the reanalysis, whereas the CMIP5/6 models capture ~ 58% of the responses. Further analysis indicates that these underestimated circulation responses could be partially attributed to the biases in the precipitation scheme in both the atmospheric and coupled models, as well as the biases in the simulated ENSO-related SST patterns in the coupled models. One should pay special attention to these biases when studying the WC or the tropical atmosphere–ocean interactions using numerical models. [ABSTRACT FROM AUTHOR]

In this study, effect of PEDOT:PSS content on structure and properties of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)/poly(vinyl alcohol) (PVA) composite conducting fiber was systematically investigated for the first time. PEDOT:PSS/PVA composite conducting fibers with various PEDOT:PSS loadings were successfully fabricated via wet-spinning technique. Correlation between PEDOT:PSS loading and performance of composite fibers was investigated by analyzing changes in chemical constitution, morphology, thermal property, conductivity, and tensile property of composite fibers. Formation of hydrogen bonding interactions was observed between PVA matrix and PEDOT:PSS conducting filler, and the interaction was enhanced with increasing PEDOT:PSS loading. As PEDOT:PSS loading increased in composite fiber, fiber conductivity increased monotonically, and surface morphology of composite fibers became regularly circular. Young's modulus and tensile strength of composite fibers also increased with increasing PEDOT:PSS loading, while elongation at break decreased. In addition, thermal stability of composite fibers improved with increasing PEDOT:PSS loading. [ABSTRACT FROM AUTHOR]

Acetylcholinesterase (AChE) inhibitory activity test is one of the important areas of natural product research, which is traditionally tested by spectrophotometry. In this work, a simple high-performance liquid chromatography (HPLC) method was developed for testing AChE inhibitory activity in several natural products. Using galanthamine hydrobromide and huperzine A as positive controls, it was found that the optimal conditions for sample preparation are 7.0-8.0 for pH, 30 min for reaction time, 37 °C for reaction temperature, 1.1 × 10−3 U mL−1 for concentration of AChE, and 0.625 mM for acetylthiocholine iodide in the final reaction mixture with total volume 2 mL. The Diamonsil C18 column was used and the chromatographic conditions were mobile phase methanol-water-triethylamine (40:60:0.05, v/v/v), flow rate 1.0 mL min−1, injection volume 5 μL, run time 5 min, column temperature 37 °C, and wavelength 405 nm. The AChE inhibitory activity of anthocyanin with concentration of 10, 20, and 50 μg mL−1, blueberry extract and purple potato extract with concentration of 20, 100, and 500 μg mL−1 were further determined under this conditions. The results showed the inhibition ratios obtained from spectrophotometry were nearly adjacent and approximately lower than 10% and the values of absorbance mostly exceed 0.8, but the absorbance should ensure in the range of 0.15-0.8 to guarantee smaller relative error for spectrophotometry. While the inhibition ratios gained from HPLC method were higher than 20% and had greater difference, they had better comparability to the different concentrations of anthocyanin and its extracts. It is revealed that the HPLC method can be used for the evaluation of the AChE inhibitory activity in natural product extracts with deep color or not. [ABSTRACT FROM AUTHOR]

Critical and major operations are often accompanied by brain ischemic complications. Previous studies found that propofol post-conditioning provided neuroprotective functions through upregulating the expression of potassium chloride cotransporter 2 (KCC2) in gamma-aminobutyric acid (GABA) interneurons. Membrane expression and phosphorylation represents KCC2 activity, which were modulated by a protein kinase C (PKC)-dependent mechanism. However, the role of propofol in increasing KCC2 phosphorylation and the involvement of protein kinase Mζ (PKMζ), a major subtype of PKC, in the KCC2 pathway remained unclear. In this study, we established middle cerebral artery occlusion model in rats to evaluate the long-term recovery of brain functions using behavioral experiments. KCC2 and PKMζ were assessed via western blot. We used the selective inhibitor, zeta inhibitory peptide (ZIP), to investigate the relationship between KCC2 and PKMζ. Intracellular chloride concentration in the hippocampal CA1 area was measured to determine KCC2 activity. We found that propofol, infused at a speed of 20 mg kg−1 h−1 for 2 h at the onset of reperfusion, improved neurological deficits and cognitive dysfunction following ischemia/reperfusion injury. PKMζ expression was significantly upregulated, which improved KCC2 membrane expression and phosphorylation in the ischemic hippocampal CA1 area, and these effects could last up to 28 days. But ZIP inhibited this process. Ultimately, we showed that propofol increased KCC2 phosphorylation and PKMζ was the upstream of KCC2. Propofol led to long-term recovery of brain functions by upregulating the activity of the PKMζ/KCC2 pathway. [ABSTRACT FROM AUTHOR]

Galinsoga quadriradiata is an invasive weed in many parts of the world, and are causing serious damages to local biodiversity and agriculture. In this study, its complete chloroplast genome was assembled from the whole-genome Illumina sequencing data. The circular genome is 151,917 bp long, and comprises a pair of inverted repeat regions (IRs, 25,041 bp each), a large single-copy region (LSC, 83,620 bp) and a small single-copy region (SSC, 18,215 bp). It encodes a total of 111 gene species (80 protein-coding, 27 tRNA and four rRNA species), with 21 of them occurring in double copies. Introns were detected in ten PCG and six tRNA species. The nucleotide composition is asymmetric (31.07% A, 18.58% C, 19.08% G & 31.27% T) with an overall A + T content of 62.34%. Phylogenetic analysis challenged the traditional taxonomic framework of the family Asteraceae, and indicated that G. quadriradiata was relatively close to Guizotia abyssinica in phylogeny. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a toxic heavy metal that can induce apoptosis. Selenium (Se) is a necessary trace element and can antagonize the toxicity of many heavy metals, including Cd. PI3K/AKT/Bcl-2 is a key survival signaling pathway that regulates cellular defense system against oxidative injury as well as cell proliferation, survival, and apoptosis. The antagonistic effects of Se on Cd-induced toxicity have been reported. However, little is known about the effect of Se on Cd-induced apoptosis in chicken kidneys via the PI3K/AKT/Bcl-2 signaling pathway. In the present study, we fed chickens with Se, Cd, or both Se and Cd supplements, and after 90 days of treatment, we detected the related index. The results showed that the activity of inducible nitric oxide synthase (iNOS) and concentration of nitric oxide (NO) were increased; activities of the mitochondrial respiratory chain complexes (complexes I, II, and V) and ATPases (the Na-K-ATPase, the Mg-ATPase, and the Ca-ATPase) were decreased; expression of PI3K, AKT, and Bcl-2 were decreased; and expression of Bax, Bak, P53, Caspase-3, Caspase-9, and cytochrome c (Cyt c) were increased. Additionally, the results of the TUNEL assay showed that the number of apoptotic cells was increased in the Cd group. By contrast, there was a significant improvement of the correlation indicators and occurrence of apoptosis in the Se + Cd group compared to the Cd group. In conclusion, our results confirmed that Se had a positive effect on ameliorating Cd-induced apoptosis in chicken kidney tissue by activating the PI3K/AKT/Bcl-2 signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: To investigated the involvement of pulmonary function impairment in ulcerative colitis (UC), to explore a scientific basis for the Chinese medicine (CM) theory of exterior-interior correlation between Lung (Fei) and Large intestine (Dachang). Methods: Totally 120 patients with a diagnosis of UC were recruited and the demographics, clinical data, and blood samples were collected. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) concentrations were measured. Every patient accepted pulmonary function test and took chest radiograph (CXR).> Results: Pulmonary function abnormalities were present in 72 of 120 patients. The median (interquartile range) vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV), carbon monoxide diffusion capacity (DL) of lung, total lung capacity (TLC) and functional residual volume (FRV) were decreased in distal UC and pancolitis compared with ulcerative prochitis ( P <0.0005). Male patients had increased VC, FEV/FVC, and residual volume (RV)/TLC compared with female ( P <0.0005), but decreased DL and carbon monoxide iffusion capacity (K) of lung/alveolar ventilation ( P <0.0005). Age was strongly correlated with RV (Spearman rank correlation coefficient (rs)=−0.57, P <0.0001), and RV/TLC (rs=0.48, P<0.0001). Age was also correlated with FEV/FVC (rs=−0.29, P=0.001), forced expiratory flow in 75% vital capacity (FEF75%, rs=−0.20, P=0.03), DL (rs=−0.21, P=0.02), TLC (rs=−0.25, P=0.006), and FRV (rs=−0.28, P=0.002). The course of disease was correlated with FEF75% (rs=−0.18, P=0.049) and K (rs=−0.19, P=0.036). Chest radiograph abnormalities were presented in 38 of 120. Pulmonary symptoms were presented in 10 of 120. Other extraintestinal complications were presented in 21 of 120. Conclusions: Pulmonary function impairment was more frequently than other extraintestinal complications in UC patients, which may be affected by sex, age, extent and course of disease. These results may be a scientific basis for the theory of exterior-interior correlation between Lung and Large intestine. [ABSTRACT FROM AUTHOR]

The myrmicine ant Vollenhovia emeryi is native to East Asia, but has recently become established in North America. In this study, its complete mitochondrial genome has been assembled from Illumina Miseq sequencing data with a good coverage (22.5X). The circular genome is 16,259 bp in length, and harbors 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNAs genes and one control region. The control region is characterized by its remarkably high A + T content (90.61 %) and the presence of a repeat region (105 bp), which is composed of five 21-bp-long repeat motifs ('TAATT ATATT ATATA TATCA T'). All PCGs are initiated with the typical ATN codons, and are terminated with either TAA or the incomplete TA(a)/T(aa) codon. The overall nucleotide composition is highly asymmetric (39.55 % A, 17.27 % C, 6.60 % G and 36.58 % T) with an overall A + T content of 76.13 %. [ABSTRACT FROM AUTHOR]