Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays.

Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq). We applied Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas (MOSTA), which maps with single-cell resolution and high sensitivity the kinetics and directionality of transcriptional variation during mouse organogenesis. We used this information to gain insight into the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues such as the dorsal midbrain. Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development.

Single-Cell Sequencing of Peripheral Mononuclear Cells Reveals Distinct Immune Response Landscapes of COVID-19 and Influenza Patients.

The coronavirus disease 2019 (COVID-19) pandemic poses a current world-wide public health threat. However, little is known about its hallmarks compared to other infectious diseases. Here, we report the single-cell transcriptional landscape of longitudinally collected peripheral blood mononuclear cells (PBMCs) in both COVID-19- and influenza A virus (IAV)-infected patients. We observed increase of plasma cells in both COVID-19 and IAV patients and XIAP associated factor 1 (XAF1)-, tumor necrosis factor (TNF)-, and FAS-induced T cell apoptosis in COVID-19 patients. Further analyses revealed distinct signaling pathways activated in COVID-19 (STAT1 and IRF3) versus IAV (STAT3 and NFκB) patients and substantial differences in the expression of key factors. These factors include relatively increase of interleukin (IL)6R and IL6ST expression in COVID-19 patients but similarly increased IL-6 concentrations compared to IAV patients, supporting the clinical observations of increased proinflammatory cytokines in COVID-19 patients. Thus, we provide the landscape of PBMCs and unveil distinct immune response pathways in COVID-19 and IAV patients.

Cell transcriptomic atlas of the non-human primate Macaca fascicularis.

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.

PARP1 UFMylation ensures the stability of stalled replication forks.

The S-phase checkpoint involving CHK1 is essential for fork stability in response to fork stalling. PARP1 acts as a sensor of replication stress and is required for CHK1 activation. However, it is unclear how the activity of PARP1 is regulated. Here, we found that UFMylation is required for the efficient activation of CHK1 by UFMylating PARP1 at K548 during replication stress. Inactivation of UFL1, the E3 enzyme essential for UFMylation, delayed CHK1 activation and inhibits nascent DNA degradation during replication blockage as seen in PARP1-deficient cells. An in vitro study indicated that PARP1 is UFMylated at K548, which enhances its catalytic activity. Correspondingly, a PARP1 UFMylation-deficient mutant (K548R) and pathogenic mutant (F553L) compromised CHK1 activation, the restart of stalled replication forks following replication blockage, and chromosome stability. Defective PARP1 UFMylation also resulted in excessive nascent DNA degradation at stalled replication forks. Finally, we observed that PARP1 UFMylation-deficient knock-in mice exhibited increased sensitivity to replication stress caused by anticancer treatments. Thus, we demonstrate that PARP1 UFMylation promotes CHK1 activation and replication fork stability during replication stress, thus safeguarding genome integrity.

Uncovering the Bronchoalveolar Single-Cell Landscape of Patients With Pulmonary Tuberculosis With Human Immunodeficiency Virus Type 1 Coinfection.

BACKGROUND: Coinfection of human immunodeficiency virus type 1 (HIV-1) is the most significant risk factor for tuberculosis (TB). The immune responses of the lung are essential to restrict the growth of Mycobacterium tuberculosis and avoid the emergence of the disease. Nevertheless, there is still limited knowledge about the local immune response in people with HIV-1-TB coinfection. METHODS: We employed single-cell RNA sequencing (scRNA-seq) on bronchoalveolar lavage fluid from 9 individuals with HIV-1-TB coinfection and 10 with pulmonary TB. RESULTS: A total of 19 058 cells were grouped into 4 major cell types: myeloid cells, T/natural killer (NK) cells, B cells, and epithelial cells. The myeloid cells and T/NK cells were further divided into 10 and 11 subsets, respectively. The proportions of dendritic cell subsets, CD4+ T cells, and NK cells were lower in the HIV-1-TB coinfection group compared to the TB group, while the frequency of CD8+ T cells was higher. Additionally, we identified numerous differentially expressed genes between the CD4+ and CD8+ T-cell subsets between the 2 groups. CONCLUSIONS: HIV-1 infection not only affects the abundance of immune cells in the lungs but also alters their functions in patients with pulmonary TB.

Engineering applications of solar photocatalysis & photothermal catalysis for hydrogen production from biomass:A review.

Biomass photoreforming is a promising way of producing sustainable hydrogen thanks to the abundant sources of biomass feedstocks. Solar energy provides the heat and driven force to initial biomass oxidation coupled with H2 evolution. Currently, biomass photoreforming is still far from plant-scale applications due to the lower solar energy utilization efficiencies, the low H2 yield, and the lack of appropriate photoreactors. The production of H2 from photoreforming of native biomass and platform molecules was summarized and discussed with special attention to the prospects of scaling up the catalysis technology for mass production of hydrogen. The types of photoreforming including photocatalysis and photothermal catalysis were discussed consequently considering the different requirements for photoreactors. We also reviewed the photoreactors that support biomass photoreforming. Numerical simulation methods were implemented for the solid-liquid two-phase flow and inter-particle radiative transfer involved in the reaction process. Developing concentrated photothermal catalytic flowed reactors is beneficial to scale-up catalytic hydrogen production from biomass.

Comparison of the efficacy of neuronavigation-assisted intracerebral hematoma puncture and drainage with neuroendoscopic hematoma removal in treatment of hypertensive cerebral hemorrhage.

OBJECTIVE: To compare neuronavigation-assisted intracerebral hematoma puncture and drainage with neuroendoscopic hematoma removal for treatment of hypertensive cerebral hemorrhage. METHOD: Ninety-one patients with hypertensive cerebral hemorrhage admitted to our neurosurgery department from June 2022 to May 2023 were selected: 47 patients who underwent endoscopic hematoma removal with the aid of neuronavigation in observation Group A and 44 who underwent intracerebral hematoma puncture and drainage in control Group B. The duration of surgery, intraoperative bleeding, hematoma clearance rate, pre- and postoperative GCS score, National Institutes of Health Stroke Scale (NIHSS) score, mRS score and postoperative complications were compared between the two groups. RESULTS: The duration of surgery, intraoperative bleeding and hematoma clearance were significantly lower in Group B than in Group A (p < 0.05). Conversely, no significant differences in the preoperative, 7-day postoperative, 14-day postoperative or 1-month postoperative GCS or NIHSS scores or the posthealing mRS score were observed between Groups A and B. However, the incidence of postoperative complications was significantly greater in Group B than in Group A (p < 0.05), with the most significant difference in incidence of intracranial infection (p < 0.05). CONCLUSION: Both neuronavigation-assisted intracerebral hematoma puncture and drainage and neuroendoscopic hematoma removal are effective at improving the outcome of patients with hypertensive cerebral hemorrhage. The disadvantage of neuronavigation is that the incidence of complications is significantly greater than that of other methods; postoperative care and prevention of complications should be strengthened in clinical practice.

Combined vertical and external rotational force in plantarflexion position produces posterior pilon fracture: A preliminary cadaveric study.

BACKGROUND: Posterior pilon fracture is speculated to occur by a combination of rotation and axial load, which makes it different from rotational posterior malleolar fracture or pilon fracture, but is not validated in vitro. The aim of the current study is to investigate the injury mechanisms of posterior pilon fracture on cadaveric specimens. METHODS: Eighteen cadaveric specimens were mounted to a loading device to undergo solitary vertical loading, solitary external rotational loading, and combined vertical and external rotational loading until failure, in initial position of plantarflexion with or without varus. The fracture characteristics were documented for each specimen. RESULTS: Vertical loading force combined with external rotation force diversified the fracture types resulting in pilon fracture, tibial spiral fracture, rotational malleolar fracture, talar fracture or calcaneal fracture. Vertical violence combined with external rotational loading in position of 45° of plantarflexion and 0° of varus produced posterior pilon fracture in specimens No. 13 and 14. CONCLUSION: Combination of vertical and external rotational force in plantarflexion position on cadaveric specimens produce posterior pilon fracture.

Real-world effectiveness and factors associated with effectiveness of inactivated SARS-CoV-2 vaccines: a systematic review and meta-regression analysis.

BACKGROUND: The two inactivated SARS-CoV-2 vaccines, CoronaVac and BBIBP-CorV, have been widely used to control the COVID-19 pandemic. The influence of multiple factors on inactivated vaccine effectiveness (VE) during long-term use and against variants is not well understood. METHODS: We selected published or preprinted articles from PubMed, Embase, Scopus, Web of Science, medRxiv, BioRxiv, and the WHO COVID-19 database by 31 August 2022. We included observational studies that assessed the VE of completed primary series or homologous booster against SARS-CoV-2 infection or severe COVID-19. We used DerSimonian and Laird random-effects models to calculate pooled estimates and conducted multiple meta-regression with an information theoretic approach based on Akaike's Information Criterion to select the model and identify the factors associated with VE. RESULTS: Fifty-one eligible studies with 151 estimates were included. For prevention of infection, VE associated with study region, variants, and time since vaccination; VE was significantly decreased against Omicron compared to Alpha (P = 0.021), primary series VE was 52.8% (95% CI, 43.3 to 60.7%) against Delta and 16.4% (95% CI, 9.5 to 22.8%) against Omicron, and booster dose VE was 65.2% (95% CI, 48.3 to 76.6%) against Delta and 20.3% (95% CI, 10.5 to 28.0%) against Omicron; primary VE decreased significantly after 180 days (P = 0.022). For the prevention of severe COVID-19, VE associated with vaccine doses, age, study region, variants, study design, and study population type; booster VE increased significantly (P = 0.001) compared to primary; though VE decreased significantly against Gamma (P = 0.034), Delta (P = 0.001), and Omicron (P = 0.001) compared to Alpha, primary and booster VEs were all above 60% against each variant. CONCLUSIONS: Inactivated vaccine protection against SARS-CoV-2 infection was moderate, decreased significantly after 6 months following primary vaccination, and was restored by booster vaccination. VE against severe COVID-19 was greatest after boosting and did not decrease over time, sustained for over 6 months after the primary series, and more evidence is needed to assess the duration of booster VE. VE varied by variants, most notably against Omicron. It is necessary to ensure booster vaccination of everyone eligible for SARS-CoV-2 vaccines and continue monitoring virus evolution and VE. TRIAL REGISTRATION: PROSPERO, CRD42022353272.

Differential changes in the gut microbiota between extrinsic and intrinsic atopic dermatitis.

Elevated serum level of total and (or) allergen-specific IgE is one of the key features of atopic dermatitis (AD). Previous studies have shown that the gut microbiome mediates interactions between external exposures and the immune system in AD; however, the relationship between the gut microbiota and IgE remains unclear. In the present study, analyses of environmental exposures for 250 AD patients and 138 healthy volunteers revealed an association between hygiene levels in the residential environment and the occurrence of AD and the IgE level. Metagenomic sequencing of the gut microbiota from 68 AD patients and 77 healthy controls showed that AD patients had a distinct gut microbiota composition; moreover, while L-histidine degradation was enriched in healthy controls, L-histidine biosynthesis was enriched in AD patients. Extrinsic and intrinsic AD showed different enrichment patterns of specific microbes and differential associations of functional pathways. Our study indicated that elevated levels of IgE in AD were related to specific microbes in the gut microbiota, which showed extensive interactions with environmental factors.

Participation of protein metabolism in cancer progression and its potential targeting for the management of cancer.

Cancer malignancies may broadly be described as heterogeneous disorders manifested by uncontrolled cellular growth/division and proliferation. Tumor cells utilize metabolic reprogramming to accomplish the upregulated nutritional requirements for sustaining their uncontrolled growth, proliferation, and survival. Metabolic reprogramming also called altered or dysregulated metabolism undergoes modification in normal metabolic pathways for anabolic precursor's generation that serves to continue biomass formation that sustains the growth, proliferation, and survival of carcinogenic cells under a nutrition-deprived microenvironment. A wide range of dysregulated/altered metabolic pathways encompassing different metabolic regulators have been described; however, the current review is focused to explain deeply the metabolic pathways modifications inducing upregulation of proteins/amino acids metabolism. The essential modification of various metabolic cycles with their consequent outcomes meanwhile explored promising therapeutic targets playing a pivotal role in metabolic regulation and is successfully employed for effective target-specific cancer treatment. The current review is aimed to understand the metabolic reprogramming of different proteins/amino acids involved in tumor progression along with potential therapeutic perspective elucidating targeted cancer therapy via these targets.

Circ_0082182 upregulates the NFIB level via sponging miR-326 to promote oxaliplatin resistance and malignant progression of colorectal cancer cells.

Circular RNAs (circRNAs) are key regulators in tumor metastasis and drug resistance. This study was designed to investigate circ_0082182 function and mechanism in oxaliplatin (OXA) resistance and cancer progression of colorectal cancer (CRC). The circ_0082182, microRNA-326 (miR-326), and nuclear factor I B (NFIB) levels were quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell sensitization was analyzed by Cell Counting Kit-8 assay. The proliferation ability was determined via EdU assay, and apoptosis was measured by flow cytometry. Transwell assay and wound healing assay were performed to assess cell invasion and migration. The protein level was examined through Western blot. The binding interaction was conducted via dual-luciferase reporter assay. Xenograft tumor assay was used to explore the circ_0082182 function in vivo. The circ_0082182 level was upregulated in OXA-resistant CRC samples and cells. Downregulation of circ_0082182 suppressed OXA resistance, proliferation, invasion, and migration but promoted apoptosis of OXA-resistant CRC cells. Circ_0082182 acted as a sponge for miR-326. The regulatory role of circ_0082182 was ascribed to the miR-326 sponging function. MiR-326 directly targeted NFIB to impede OXA resistance and cancer progression in CRC cells. NFIB level was regulated by circ_0082182 via sponging miR-326. Circ_0082182 promoted tumor growth in OXA-resistant xenograft tumor model through mediating the miR-326/NFIB axis. These data suggested that circ_0082182 elevated the NFIB expression to regulate OXA resistance and CRC progression by absorbing miR-326.

Microbiota DNA Translocation Into Mesentery Lymph Nodes Is Associated With Early Development of Pouchitis After IPAA for Ulcerative Colitis.

BACKGROUND: The role of bacterial translocation in Crohn's disease has been extensively studied. However, data regarding bacterial translocation into the mesentery in patients with ulcerative colitis were scarce. OBJECTIVE: This study aimed to explore the relationship between bacterial translocation and postoperative outcome by comparing the microbiome profile of different anatomical sites in patients with ulcerative colitis who underwent proctocolectomy and IPAA. DESIGN: A prospective study. SETTING: This study was conducted at the Jinling Hospital from August 2017 to May 2018. PATIENTS: Samples of 27 patients with ulcerative colitis who had IPAA and 15 healthy controls who underwent routine colonoscopy were collected. MAIN OUTCOME MEASURES: The microbiome profile of different tissue sites and short- and long-term outcomes after IPAA in patients with ulcerative colitis. RESULTS: Bacterial DNA was detected in mesenteric lymph nodes of 51.9% of patients with ulcerative colitis (14/27) and in mesenteric adipose tissue of 66.7% of patients (18/27). The microbiome in mesenteric lymph nodes and mesenteric adipose tissue resembled the mucosal microbiome to a greater extent than the fecal microbiome. Positive bacterial DNA in mesenteric lymph nodes (8/14 vs 0/13; p = 0.002) was associated with pouchitis within 12 months after IPAA, whereas Bray-Curtis distance in mesenteric lymph nodes was significantly different between patients with pouchitis and without ( p = 0.009). LIMITATIONS: This study was limited by its small sample size and lacked situ experiment to confirm the true bacterial translation. CONCLUSIONS: Bacterial translocation was highly prevalent in patients with ulcerative colitis. The translocated bacteria DNA in mesenteric adipose tissue and mesenteric lymph nodes was highly correlated and more likely to originate from mucosal than fecal microbiome. Also, the extent of bacterial translocation and translocation of certain bacteria might be associated with the early development of pouchitis after IPAA. This might represent an unprecedented technique to predict pouchitis using mesenteric lymph node bacterial profiles. See Video Abstract at http://links.lww.com/DCR/C119 . LA TRANSLOCACIN DEL ADN DE LA MICROBIOTA EN LOS GANGLIOS LINFTICOS DEL MESENTERIO SE ASOCIA CON EL DESARROLLO TEMPRANO DE POUCHITIS DESPUS DE IPAA PARA LA COLITIS ULCEROSA: ANTECEDENTES:El papel de la translocación bacteriana en la enfermedad de Crohn se ha estudiado ampliamente en los últimos años. Sin embargo, los datos sobre la translocación bacteriana en el mesenterio en pacientes con colitis ulcerosa fueron escasos.OBJETIVO:El objetivo de este estudio fue explorar la relación entre la translocación bacteriana y el resultado postoperatorio comparando el perfil del microbioma de diferentes sitios anatómicos en pacientes con colitis ulcerosa que se sometieron a proctocolectomía y anastomosis ileoanal con bolsa.DISEÑO:Estudio prospectivo.AJUSTE:Este estudio se realizó en el Hospital Jinling desde agosto de 2017 hasta mayo de 2018.PACIENTES:Se recogieron muestras de 27 pacientes con colitis ulcerosa que tenían anastomosis de bolsa ileoanal y 15 controles sanos que se sometieron a una colonoscopia de rutina.PRINCIPALES MEDIDAS DE RESULTADO:El perfil del microbioma de diferentes sitios de tejido y los resultados a corto y largo plazo después de la anastomosis ileoanal con bolsa en pacientes con colitis ulcerosa.RESULTADOS:Se detectó ADN bacteriano en los ganglios linfáticos mesentéricos del 51,9 % (14/27) de los pacientes con colitis ulcerosa y en el tejido adiposo mesentérico del 66,7 % (18/27) de los pacientes, respectivamente. El microbioma en los ganglios linfáticos mesentéricos y el tejido adiposo mesentérico se parecía más al microbioma de la mucosa que al microbioma fecal. El ADN bacteriano translocado en los ganglios linfáticos mesentéricos y el tejido adiposo mesentérico estaban altamente correlacionados. El ADN bacteriano positivo en los ganglios linfáticos mesentéricos (8/14 frente a 0/13, p = 0,002) se asoció con reservoritis dentro de los 12 meses posteriores a la anastomosis ileoanal con reservorio, mientras que la distancia de Bray-Curtis en los ganglios linfáticos mesentéricos fue significativamente diferente entre reservoritis y no reservorios. -pacientes con reservorio (p = 0,009). Ruminococcus, Bacteroides y Clostridiales se encontraron exclusivamente en los ganglios linfáticos mesentéricos de pacientes con reservoritis.LIMITACIÓN:Este estudio estuvo limitado por el pequeño tamaño de la muestra y la falta de un experimento in situ para confirmar la verdadera traducción bacteriana.CONCLUSIÓN:La translocación bacteriana fue altamente prevalente en pacientes con colitis ulcerosa. El ADN bacteriano translocado en el tejido adiposo mesentérico y los ganglios linfáticos mesentéricos estaba altamente correlacionado y era más probable que se originara en el microbioma de la mucosa que en el fecal. Además, la extensión de la translocación bacteriana y la translocación de ciertas bacterias podría estar asociada con el desarrollo temprano de reservoritis después de la anastomosis del reservorio ileoanal. Esto podría representar una técnica sin precedentes para predecir la reservoritis utilizando perfiles bacterianos de los ganglios linfáticos mesentéricos. Consulte Video Resumen en. http://links.lww.com/DCR/C119(Traducción-Dr. Felipe Bellolio ).

Electrochemical selenium-catalyzed para-amination of N-aryloxyamides: access to polysubstituted aminophenols.

Aminophenols are a class of important compounds with various pharmacological activities such as anticancer, anti-inflammatory, antimalarial, and antibacterial activities. Herein, we introduce a mild and efficient electrochemical selenium-catalyzed strategy to synthesize polysubstituted aminophenols. High atom efficiency and transition metal-free and oxidant-free conditions are the striking features of this protocol. By merging electrochemical and organoselenium-catalyzed processes, the intramolecular rearrangement of N-aryloxyamides produces para-amination products at room temperature in a simple undivided cell.

Cu-MOF derived CuO@g-C3N4 nanozyme for cascade catalytic colorimetric sensing.

The use of peroxidase mimics has great potential for various real applications due to their strong catalytic activity. Herein, a facile strategy was proposed to directly prepare CuO@g-C3N4 by Cu-MOF derivatization and demonstrated its efficacy in constructing a multiple enzymatic cascade system by loading protein enzymes onto it. The resulting CuO@g-C3N4 possessed high peroxidase-like activity, with a Michaelis constant (Km) of 0.25 and 0.16 mM for H2O2 and 3,3',5,5'-tetramethylbenzidine (TMB), respectively. Additionally, the high surface area of CuO@g-C3N4 facilitated the loading of protein enzymes and maintained their activity over an extended period, expanding the potential applications of CuO@g-C3N4. To test its feasibility, CuO@g-C3N4/protein oxidase complex was prepared and used to sense the ripeness and freshness of fruits and meat, respectively. The mechanism relied on the fact that the ripeness of fruits increased and freshness of food decreased with the release of marked targets, such as glucose and xanthine, which could produce H2O2 when digested by the corresponding oxidase. The peroxidase mimics of CuO@g-C3N4 could then sensitively colorimetric detect H2O2 in present of TMB. The obtained CuO@g-C3N4/oxidase complex exhibited an excellent linear response to glucose or xanthine in the range of 1.0-120 µmol/L or 8.0-350 µmol/L, respectively. Furthermore, accurate quantification of glucose and xanthine in real samples is achieved with spiked recoveries ranging from 80.2% to 120.0% and from 94.2% to 112.0%, respectively. Overall, this work demonstrates the potential of CuO@g-C3N4 in various practical applications, such as food freshness detection.

Differences in Cortical Activation During Dorsiflexion and Plantarflexion in Chronic Ankle Instability: A Task-fMRI Study.

BACKGROUND: Chronic ankle instability is a common sports injury that often presents with increased plantarflexion and restricted dorsiflexion. The cumulative effect of peripheral injuries may induce neuroplasticity in the central nervous system. However, the relationship between dorsiflexion or plantarflexion and the central nervous system in patients with chronic ankle instability remains unknown. QUESTIONS/PURPOSES: (1) Is there a difference in region and voxel (volume pixel) of cortical activation during plantarflexion and dorsiflexion between patients with chronic ankle instability and a control group with normal ankle function? (2) Is there a correlation between activation of sensorimotor-related brain regions and three clinical measurement scales of ankle function and disease severity in patients with chronic ankle instability? METHODS: Between December 2020 and May 2022, we treated 400 patients who had chronic ankle instability. Ten percent (40 patients; mean ± standard deviation age 29 ± 7 years; 17 male patients) were randomly selected to participate in this study. We recruited 42 volunteers with normal ankle function (mean age 28 ± 5 years; 21 male participants) matched by age and education level. A total of 2.5% (1 of 40) of patients with bilateral chronic ankle instability and 30% (12 of 40) with left-sided chronic ankle injury did not meet our inclusion criteria and were excluded from the study. The control group underwent MRI with good image quality. Finally, 27 patients with chronic ankle instability (mean age 26 ± 5 years; 10 male patients) and 42 participants with normal ankle function were enrolled. Ankle function and disease severity were assessed using three clinical scales: the Cumberland Ankle Instability Tool, Karlsson-Peterson Ankle Function Score, and the American Orthopedic Foot and Ankle Society Score. A uniplanar and nonweightbearing ankle dorsiflexion-plantarflexion paradigm (a recognized model or pattern) was performed using a short-block design during the functional MRI scan. This experimental design included a series of on-off periods consisting of movement and a rest period. From 15° of plantarflexion to 15° of dorsiflexion, the manipulator allowed 30° of ankle rotation. The cerebral excitability patterns between patients with chronic ankle instability and controls were analyzed using t-tests. We retained voxels with p values less than 0.05 in a voxel-level family-wise error correction. Clusters with voxel numbers greater than 10 were retained. The Cohen d coefficient was used to calculate between-group effect sizes. Spearman analysis was performed to explore the correlation between activation regions and the three clinical assessment scales. RESULTS: In the patient group, cortical activation was greater during plantarflexion than during dorsiflexion, which was different from that in the control group. The between-group comparison showed that patients with chronic ankle instability had reduced activation in the ipsilateral precuneus (cluster size = 35 voxels [95% CI -0.23 to 0.07]; p < 0.001) during dorsiflexion, whereas during plantarflexion, chronic ankle instability caused increased activation in the ipsilateral superior temporal gyrus (cluster size = 90 voxels [95% CI -0.73 to -0.13]; p < 0.001), precuneus (cluster size = 18 voxels [95% CI -0.56 to -0.19]; p < 0.001), supplementary motor area (cluster size = 57 voxels [95% CI -0.31 to 0.00]; p < 0.001), superior frontal gyrus (cluster size = 43 voxels [95% CI -0.82 to -0.29]; p < 0.001), medial part of the superior frontal gyrus (cluster size = 39 voxels [95% CI 0.41 to 0.78]; p < 0.001), and contralateral postcentral gyrus (cluster size = 100 voxels [95% CI -0.32 to 0.02]; p < 0.001). Patients with chronic ankle instability showed a large effect size compared with controls (Cohen d > 0.8). During plantarflexion, the number of activated voxels in the supplementary motor area had a modest, positive correlation with the Karlsson-Peterson Ankle Function Score (r = 0.52; p = 0.01), and the number of activated voxels in the primary motor cortex (M1) and primary sensory cortex (S1) had a weak, positive correlation with the American Orthopedic Foot and Ankle Society Score in patients with chronic ankle instability (M1: r = 0.45; p = 0.02, S1: r = 0.49; p = 0.01). CONCLUSION: Compared with volunteers with normal ankle function, patients with chronic ankle instability had increased cortical activation during plantarflexion and decreased cortical activation during dorsiflexion. We analyzed the central neural mechanisms of chronic ankle instability in patients with sports injuries and provided a theoretical basis for the development of new central and peripheral interventions in the future. CLINICAL RELEVANCE: Because there was a positive correlation between the neural activity in sensorimotor-related regions during plantarflexion and clinical severity, clinicians might one day be able to help patients who have chronic ankle instability with neuromuscular rehabilitation by applying electrical stimulation to specific targets (such as S1M1 and the supplementary motor area) or by increasing activation of sensorimotor neurons through ankle movement.

How do different arsenic species affect the joint toxicity of perfluorooctanoic acid and arsenic to earthworm Eisenia fetida: A multi-biomarker approach.

Perfluorooctanoic acid (PFOA) and arsenic are widely distributed pollutants and can coexist in the environment. However, no study has been reported about the effects of different arsenic species on the joint toxicity of arsenic and PFOA to soil invertebrates. In this study, four arsenic species were selected, including arsenite (As(III)), arsenate (As(V)), monomethylarsonate (MMA), and dimethylarsinate (DMA). Earthworms Eisenia fetida were exposed to soils spiked with sublethal concentrations of PFOA, different arsenic species, and their binary mixtures for 56 days. The bioaccumulation and biotransformation of pollutants, as well as eight biomarkers in organisms, were assayed. The results indicated that the coexistence of PFOA and different arsenic species in soils could enhance the bioavailability of arsenic species while reducing the bioavailability of PFOA, and inhibit the arsenic biotransformation process in earthworms. Responses of most biomarkers in joint treatments of PFOA and As(III)/As(V) showed more significant variations compared with those in single treatments, indicating higher toxicity to the earthworms. The Integrated Biomarker Response (IBR) index was used to integrate the multi-biomarker responses, and the results also exhibited enhanced toxic effects in combined treatments of inorganic arsenic and PFOA. In comparison, both the biomarker variations and IBR values were lower in joint treatments of PFOA and MMA/DMA. Then the toxic interactions in the binary mixture systems were characterized by using a combined method of IBR and Effect Addition Index. The results revealed that the toxic interactions of the PFOA/arsenic mixture in earthworms depended on the different species of arsenic. The combined exposure of PFOA with inorganic arsenic led to a synergistic interaction, while that with organic arsenic resulted in an antagonistic response. Overall, this study provides new insights into the assessment of the joint toxicity of perfluoroalkyl substances and arsenic in soil ecosystems.

AKG induces cell apoptosis by inducing reactive oxygen species-mediated endoplasmic reticulum stress and by suppressing PI3K/AKT/mTOR-mediated autophagy in renal cell carcinoma.

BACKGROUND: Alpha-ketoglutarate (AKG) or 2-oxoglutarate is a key substance in the tricarboxylic acid cycle (TCA) and has been known to play an important role in cancerogenesis and tumor progression. Renal cell carcinoma (RCC) is the most common type of kidney cancer, and it has a high mortality rate. Autophagy is a phenomenon of self-digestion, and its significance in tumor genesis and progression remains debatable. However, the mechanisms underlying how AKG regulates autophagy in RCC remain unknown. Thus, the purpose of this study was to assess the therapeutic efficacy of AKG and its molecular mechanisms. METHODS: RCC cell lines 786O and ACHN were treated with varying doses of AKG for 24 h. CCK-8, Transwell, and scratch wound healing assays were utilized to evaluate the role of AKG in RCC cells. Autophagy protein and PI3K/AKT/mTOR pathway protein levels were analyzed by Western blot. RESULTS: AKG inhibited the proliferation of RCC cells 786O and ACHN in a dose-dependent manner according to the CCK-8 assay. In addition, flow cytometry and Western blot analysis revealed that AKG dose-dependently triggered apoptosis and autophagy in RCC cells. By promoting cell apoptosis and autophagy, AKG dramatically suppressed tumor growth. Mechanistically, AKG induces autophagy by promoting ROS generation and inhibiting the PI3K/AKT/mTOR pathway. CONCLUSIONS: The anti-tumor effect of AKG promotes autophagy in renal cancer cells via mediating ROS-PI3K/Akt/mTOR, and may be used as a potential anticancer drug for kidney cancer.

Student Learning Behavior Recognition Incorporating Data Augmentation with Learning Feature Representation in Smart Classrooms.

A robust and scientifically grounded teaching evaluation system holds significant importance in modern education, serving as a crucial metric that reflects the quality of classroom instruction. However, current methodologies within smart classroom environments have distinct limitations. These include accommodating a substantial student population, grappling with object detection challenges due to obstructions, and encountering accuracy issues in recognition stemming from varying observation angles. To address these limitations, this paper proposes an innovative data augmentation approach designed to detect distinct student behaviors by leveraging focused behavioral attributes. The primary objective is to alleviate the pedagogical workload. The process begins with assembling a concise dataset tailored for discerning student learning behaviors, followed by the application of data augmentation techniques to significantly expand its size. Additionally, the architectural prowess of the Extended-efficient Layer Aggregation Networks (E-ELAN) is harnessed to effectively extract a diverse array of learning behavior features. Of particular note is the integration of the Channel-wise Attention Module (CBAM) focal mechanism into the feature detection network. This integration plays a pivotal role, enhancing the network's ability to detect key cues relevant to student learning behaviors and thereby heightening feature identification precision. The culmination of this methodological journey involves the classification of the extracted features through a dual-pronged conduit: the Feature Pyramid Network (FPN) and the Path Aggregation Network (PAN). Empirical evidence vividly demonstrates the potency of the proposed methodology, yielding a mean average precision (mAP) of 96.7%. This achievement surpasses comparable methodologies by a substantial margin of at least 11.9%, conclusively highlighting the method's superior recognition capabilities. This research has an important impact on the field of teaching evaluation system, which helps to reduce the burden of educators on the one hand, and makes teaching evaluation more objective and accurate on the other hand.

Dealloyed Porous NiFe2O4/NiO with Dual-Network Structure as High-Performance Anodes for Lithium-Ion Batteries.

As high-capacity anode materials, spinel NiFe2O4 aroused extensive attention due to its natural abundance and safe working voltage. For widespread commercialization, some drawbacks, such as rapid capacity fading and poor reversibility due to large volume variation and inferior conductivity, urgently require amelioration. In this work, NiFe2O4/NiO composites with a dual-network structure were fabricated by a simple dealloying method. Benefiting from the dual-network structure and composed of nanosheet networks and ligament-pore networks, this material provides sufficient space for volume expansion and is able to boost the rapid transfer of electrons and Li ions. As a result, the material exhibits excellent electrochemical performance, retaining 756.9 mAh g-1 at 200 mA g-1 after cycling for 100 cycles and retaining 641.1 mAh g-1 after 1000 cycles at 500 mA g-1. This work provides a facile way to prepare a novel dual-network structured spinel oxide material, which can promote the development of oxide anodes and also dealloying techniques in broad fields.