LncRNA SNHG14 silencing attenuates the progression of diabetic nephropathy via the miR-30e-5p/SOX4 axis.

BACKGROUND: Diabetic nephropathy (DN) is a diabetic complication. LncRNAs are reported to participate in the pathophysiology of DN. Here, the function and mechanism of lncRNA small nucleolar RNA host gene 14 (SNHG14) in DN were explored. METHODS: Streptozotocin (STZ)-induced DN mouse models and high glucose (HG)-treated human mesangial cells (MCs) were used to detect SNHG14 expression. SNHG14 silencing plasmids were applied to examine the function of SNHG14 on proliferation and fibrosis in HG-treated MCs. Potential targets of SNHG14 were predicted using bioinformatics tools and verified by luciferase reporter, RNA pulldown, and northern blotting assays. The functional role of SNHG14 in DN in vivo was detected by injection with adenoviral vector carrying sh-SNHG14 into DN mice. Serum creatinine, blood urea nitrogen, blood glucose, 24-h proteinuria, relative kidney weight, and renal pathological changes were examined in DN mice. RESULTS: SNHG14 expression was elevated in the kidneys of DN mice and HG-treated MCs. SNHG14 silencing inhibited proliferation and fibrosis of HG-stimulated MCs. SNHG14 bound to miR-30e-5p to upregulate SOX4 expression. In rescue assays, SOX4 elevation diminished the effects of SNHG14 silencing in HG-treated MCs, and SOX4 silencing reversed the effects of SNHG14 overexpression. In in vivo studies, SNHG14 downregulation significantly ameliorated renal injuries and renal interstitial fibrosis in DN mice. CONCLUSIONS: SNHG14 silencing attenuates kidney injury in DN mice and reduces proliferation and fibrotic phenotype of HG-stimulated MCs via the miR-30e-5p/SOX4 axis.

Photo-thermal synergistic CO2 hydrogenation towards CO over PtRh bimetal-decorated GaN nanowires/Si.

Photo-thermal-synergistic hydrogenation is a promising strategy for upcycling carbon dioxide into fuels and chemicals by maximally utilizing full-spectrum solar energy. Herein, by immobilizing Pt-Rh bimetal onto a well-developed GaN NWs/Si platform, CO2 was photo-thermo-catalytically hydrogenated towards CO under concentrated light illumination without extra energies. The as-designed architecture demonstrates a considerable CO evolution rate of 11.7 mol gGaN-1 h-1 with a high selectivity of 98.5% under concentrated light illumination of 5.3 W cm-2, leading to a benchmark turnover frequency of 26 486 mol CO per mol PtRh per hour. It is nearly 2-3 orders of magnitude higher than that of pure thermal catalysis under the same temperature by external heating without light. Control experiments, various spectroscopic characterization methods, and density functional theory calculations are correlatively conducted to reveal the origin of the remarkable performance as well as the photo-thermal enhanced mechanism. It is found that the recombination of photogenerated electron-hole pairs is dramatically inhibited under high temperatures arising from the photothermal effect. More critically, the synergy between photogenerated carriers arising from ultraviolet light and photoinduced heat arising from visible- and infrared light enables a sharp reduction of the apparent activation barrier of CO2 hydrogenation from 2.09 downward to 1.18 eV. The evolution pathway of CO2 hydrogenation towards CO is also disclosed at the molecular level. Furthermore, compared to monometallic Pt, the introduction of Rh further reduces the desorption energy barrier of *CO by optimizing the electronic properties of Pt, thus enabling the achievement of excellent activity and selectivity. This work provides new insights into CO2 hydrogenation by maximally utilizing full-spectrum sunlight via photo-thermal synergy.

Is P3 amplitude associated with greater gaze distraction effect in schizotypy?

A recently proposed "Hyperfocusing hypothesis" suggests that schizotypy is associated with a more narrow but more intense way of allocating attention. The current study aims to test a vital prediction of this hypothesis in a social context, that schizotypy may be related to greater difficulty overcoming the distracting effects of gaze. This could cause a longer time to respond to targets that are invalidly cued by gaze. The current study tested this prediction in a modified Posner cueing paradigm by using P3 as an indicator for attentional resources. Seventy-four young healthy individuals with different levels of schizotypy were included, they were asked to detect the location of a target that was cued validly or invalidly by the gaze and head orientation. The results revealed that (a) schizotypy is associated with hyperfocusing on gaze direction, leading to greater difficulty overcoming the distracting effect of gaze. The higher the trait-schizotypy score, the more time needed to respond to targets that were invalidly cued by gaze (b) schizotypy is associated with reduced P3 which is directed by social communicative stimuli. The higher the trait-schizotypy score, the smaller the amplitude of P3 (c) the relationship between schizotypal traits and response times of the gaze-invalid condition is fully intermediated by P3. The findings of the current study suggest the P3 component may be a crucial neural mechanism underlying joint attention deficits in schizophrenia.

Multi-hierarchy Network Configuration Can Predict Brain States and Performance.

The brain is a hierarchical modular organization that varies across functional states. Network configuration can better reveal network organization patterns. However, the multi-hierarchy network configuration remains unknown. Here, we proposed an eigenmodal decomposition approach to detect modules at multi-hierarchy, which can identify higher-layer potential submodules, and is consistent with the brain hierarchical structure. We defined three metrics: node configuration matrix, combinability, and separability. Node configuration matrix represents network configuration changes between layers. Separability reflects network configuration from global to local, whereas combinability shows network configuration from local to global. First, we created a random network to verify the feasibility of the method. Results show that separability of real networks is larger than that of random networks, whereas combinability is smaller than random networks. Then, we analyzed a large data set incorporating fMRI data from resting and seven distinct tasking conditions. Experiment results demonstrates the high similarity in node configuration matrices for different task conditions, whereas the tasking states have less separability and greater combinability between modules compared with the resting state. Furthermore, the ability of brain network configuration can predict brain states and cognition performance. Crucially, derived from tasks are highlighted with greater power than resting, showing that task-induced attributes have a greater ability to reveal individual differences. Together, our study provides novel perspectives for analyzing the organization structure of complex brain networks at multi-hierarchy, gives new insights to further unravel the working mechanisms of the brain, and adds new evidence for tasking states to better characterize and predict behavioral traits.

The associations between lumbar proprioception and postural control during and after calf vibration in people with and without chronic low back pain.

The relationships of lumbar proprioception with postural control have not been clarified in people with chronic low back pain. This study aimed to compare the associations between lumbar proprioception and postural control in response to calf vibration in individuals with and without chronic low back pain. In this study, we recruited twenty patients with chronic low back pain (CLBP group) and twenty healthy control subjects (HC group) aged between 18 and 50 years. This study was a cross-sectional study and completed from May 2022 to October 2022. The passive joint repositioning sense (PJRS) test for two positions (15° and 35°) were used to assess lumbar proprioception and expressed as the mean of reposition error (RE). Postural control was tested by adding and removing calf vibration while standing on a stable force plate with eyes closed. The sway velocity in the anterior-posterior (AP) direction of center of pressure (COP) data with a window of 15s epoch at baseline, during and after calf vibration was used to evaluate postural control. Mann-Whitney U-tests were used to compare the difference of lumbar proprioception between two groups, and the independent t-tests were used to compare the difference of postural control at baseline and during vibration, and a mixed design ANOVA was used to compare the difference of postural control during post-perturbation. In addition, to explore the association between postural control and lumbar proprioception and pain intensity, Spearman's correlations were used for each group. The major results are: (1) significantly higher PJRS on RE of 15° (CLBP: 95% CI [2.03, 3.70]; HC: 95% CI [1.03, 1.93]) and PJRS on RE of 35° (CLBP: 95% CI [2.59, 4.88]; HC: 95% CI [1.07, 3.00]) were found in the CLBP group; (2) AP velocity was not different between the CLBP group and the HC group at baseline and during calf vibration. However, AP velocity was significantly larger in the CLBP group compared with the HC group at epoch 2-14 after calf vibration, and AP velocity for the CLBP group took a longer time (23 epochs) to return to the baseline after calf vibration compared with the HC group (9 epochs); (3) lumbar proprioception represented by PJRS on RE of 15°correlated negatively with AP velocity during and after vibration for the HC group. Within the CLBP group, no significant relationships between PJRS on RE for two positions (15° and 35°) and AP velocity in any postural phases were found. In conclusion, the CLBP group has poorer lumbar proprioception, slower proprioceptive reweighting and impaired postural control after calf vibration compared to the HC group. Lumbar proprioception offers different information on the control strategy of standing control for individuals with and without CLBP in the situations with proprioceptive disturbance. These results highlight the significance of assessing lumbar proprioception and postural control in CLBP patients.

Chemical and Geological Properties of Shale Gas: In Situ Desorption of Lower Cambrian Niutitang Shale in the Micangshan Tectonic Zone of South Shaanxi, China.

Shale gas was recently found in the Lower Cambrian Niutitang Formation (LCNF) of the Micangshan tectonic zone of south Shaanxi (MTZSS), but not in commercial quantities. To determine the laws governing the generation, enrichment, and desorption of shale gases in overmatured shale strata in the LCNF of MTZSS, we carried out in situ desorption experiments on nine shale core samples and got 168 desorbed gas samples at different phases of desorption. Also measured were the chemical and carbon isotopic compositions of these desorbed gas samples and the geochemical parameters of the shale core samples. CH4 was the predominant hydrocarbon shale gas identified in the 82.06-98.48% range, suggesting that the gases were mainly dry. The nonhydrocarbon gases found were CO2 and H2. The CH4 content of the desorbed gas samples dropped continuously during desorption, lowering the dryness index to 98.48 and 92.26% of the first and last desorbed shale gas, respectively. The change in the gas ratio during shale gas desorption proved that the adsorbability of the LCNF to the various gases follows the trend H2 > CO2 > C2H6 > CH4 > He. Further, δ13C2H6 and δ13CH4 become heavier during desorption, showing isotopic fractionation arising from the desorption-diffusion coeffect. As the desorption temperature increases, the value of δ13CH4 increases because 12CH4 is more sensitive to temperature than 13CH4, so it is with the ethane. Similar to the LCNF shale gas in other areas of China, the desorbed shale gases are characteristic of carbon isotope reversal (CIR) (δ13CH4 > δ13C2H6). The cracking of the residual soluble organic matter at the high overmaturity stage mixed with the cracking of kerogen at the early stage of maturation, causing CIR. Furthermore, the desorbed gas content was proportionally and inversely related to the CIR degree and final dryness index of the desorbed gas, respectively. Moreover, the carbon isotope fractionation degree of CH4 and δ13C1 of the last desorbed gas correlated positively with the desorbed gas content and the desorbed time of the gas. In conclusion, the four parameters are effective parameters for identifying shale gas sweet spots.

Long-term impact of self-compassion training with core stability exercise on patients with nonspecific chronic low back pain: A randomized controlled trial.

OBJECTIVE: To compare the long-term effectiveness of self-compassion therapy (SCT) combined with core stability exercise (CSE) versus CSE alone in managing nonspecific chronic low back pain (NCLBP). METHODS: The combined group received SCT and CSE, while the exercise group only received CSE. Treatment was administered once weekly for four weeks, followed by one year of follow-up. The primary outcomes were changes in functional limitations (measured by Roland and Morris Disability Questionnaire scores[RMDQ]) and self-reported back pain (measured by the Numeric Pain Rating Scale[NRS]) at 52 weeks, with assessments also conducted at 2, 4, and 16 weeks. RESULTS: 52 (83.9%) completed the follow-up assessments and were included in the analysis (42 women [80.8%]; mean [SD] age,35.3 [10.0] years). In the combined group, the baseline mean (SD) RMDQ score was 9.3 (4.1),5.7 (5.8) at 2 weeks, 3.8 (3.4) at 4 weeks, 3.8 (3.7) at 16 weeks, and 2.4 (2.7) at 52 weeks. For the exercise group, the RMDQ scores were 8.2 (3.3) at baseline, 6.2 (4.2) at 2 weeks, 5.5 (4.7) at 4 weeks, 4.4 (4.5) at 16 weeks, and 5.2 (5.6) at 52 weeks. The estimated mean difference between the groups at 52 weeks was -3.356 points (95% CI, -5.835 to -0.878; P = 0.009), favoring the combined group. NRS scores showed similar changes. CONCLUSION: The addition of self-compassion therapy enhances the long-term efficacy of core stability training for NCLBP (Preregistered at chictr.org.cn:ChiCTR2100042810).

High-Throughput µPAD with Cascade Signal Amplification through Dual Enzymes for arsM in Paddy Soil.

The arsM gene is a critical biomarker for the potential risk of arsenic exposure in paddy soil. However, on-site screening of arsM is limited by the lack of high-throughput point-of-use (POU) methods. Here, a multiplex CRISPR/Cas12a microfluidic paper-based analytical device (µPAD) was constructed for the high-throughput POU analysis of arsM, with cascade amplification driven by coupling crRNA-enhanced Cas12a and horseradish peroxidase (HRP)-modified probes. First, seven crRNAs were designed to recognize arsM, and their LODs and background signal intensities were evaluated. Next, a step-by-step iterative approach was utilized to develop and optimize coupling systems, which improved the sensitivity 32 times and eliminated background signal interference. Then, ssDNA reporters modified with HRP were introduced to further lower the LOD to 16 fM, and the assay results were visible to the naked eye. A multiplex channel microfluidic paper-based chip was developed for the reaction integration and simultaneous detection of 32 samples and generated a recovery rate between 87.70 and 114.05%, simplifying the pretreatment procedures and achieving high-throughput POU analysis. Finally, arsM in Wanshan paddy soil was screened on site, and the arsM abundance ranged from 1.05 × 106 to 6.49 × 107 copies/g; this result was not affected by the environmental indicators detected in the study. Thus, a coupling crRNA-based cascade amplification method for analyzing arsM was constructed, and a microfluidic device was developed that contains many more channels than previous paper chips, greatly improving the analytical performance in paddy soil samples and providing a promising tool for the on-site screening of arsM at large scales.

Phonological properties of logographic words modulate brain activation in bilinguals: a comparative study of Chinese characters and Japanese Kanji.

The brain networks for the first (L1) and second (L2) languages are dynamically formed in the bilingual brain. This study delves into the neural mechanisms associated with logographic-logographic bilingualism, where both languages employ visually complex and conceptually rich logographic scripts. Using functional Magnetic Resonance Imaging, we examined the brain activity of Chinese-Japanese bilinguals and Japanese-Chinese bilinguals as they engaged in rhyming tasks with Chinese characters and Japanese Kanji. Results showed that Japanese-Chinese bilinguals processed both languages using common brain areas, demonstrating an assimilation pattern, whereas Chinese-Japanese bilinguals recruited additional neural regions in the left lateral prefrontal cortex for processing Japanese Kanji, reflecting their accommodation to the higher phonological complexity of L2. In addition, Japanese speakers relied more on the phonological processing route, while Chinese speakers favored visual form analysis for both languages, indicating differing neural strategy preferences between the 2 bilingual groups. Moreover, multivariate pattern analysis demonstrated that, despite the considerable neural overlap, each bilingual group formed distinguishable neural representations for each language. These findings highlight the brain's capacity for neural adaptability and specificity when processing complex logographic languages, enriching our understanding of the neural underpinnings supporting bilingual language processing.

Dynamic prediction of goal location by coordinated representation of prefrontal-hippocampal theta sequences.

Prefrontal (PFC) and hippocampal (HPC) sequences of neuronal firing modulated by theta rhythms could represent upcoming choices during spatial memory-guided decision-making. How the PFC-HPC network dynamically coordinates theta sequences to predict specific goal locations and how it is interrupted in memory impairments induced by amyloid beta (Aß) remain unclear. Here, we detected theta sequences of firing activities of PFC neurons and HPC place cells during goal-directed spatial memory tasks. We found that PFC ensembles exhibited predictive representation of the specific goal location since the starting phase of memory retrieval, earlier than the hippocampus. High predictive accuracy of PFC theta sequences existed during successful memory retrieval and positively correlated with memory performance. Coordinated PFC-HPC sequences showed PFC-dominant prediction of goal locations during successful memory retrieval. Furthermore, we found that theta sequences of both regions still existed under Aß accumulation, whereas their predictive representation of goal locations was weakened with disrupted spatial representation of HPC place cells and PFC neurons. These findings highlight the essential role of coordinated PFC-HPC sequences in successful memory retrieval of a precise goal location.

Structural characterization and ferroptosis-related immunomodulatory of a novel exopolysaccharide isolated from marine fungus Aspergillus medius.

Marine fungal exopolysaccharides play a crucial role in immunoregulation. In this investigation, a novel polysaccharide was extracted from the culture medium of the marine fungus Aspergillus medius SCAU-236. Compositional analysis revealed a structure composed of glucose units with (1,4)-α-D-Glcp, (1,3,4)-ß-D-Glcp, and (1,4,6)-α-D-Glcp, along with side chains of 1-α-D-Glcp linked to carbon 6 of (1,4,6)-α-D-Glcp and carbon 3 of (1,3,4)-ß-D-Glcp. Functional evaluations on RAW264.7 macrophage cells demonstrated Aspergillus medius polysaccharide (ASMP)'s effects on cell proliferation, nitric oxide levels, and the secretion of TNF-α, IL-6, and IL-1ß cytokines. Additionally, metabolomics indicated ASMP's potential to modulate macrophage immune function by impacting key regulatory molecules, including COX-2, iNOS, Nrf2, SLC7A11, GPX4, and ACSL4. The Nrf2/SLC7A11/GPX4 axis and ACSL4 were suggested to be involved in ASMP-induced ferroptosis, leading to increased reactive oxygen species (ROS) levels and lipid peroxidation. These findings propose a unique mechanism by which ASMP exerts immunomodulatory effects through ferroptosis induction, contributing to the understanding of marine-derived compounds in immunomodulation research.

Ultrasound Stimulation Attenuates CRS-Induced Depressive Behavior by Modulating Dopamine Release in the Prefrontal Cortex.

Depression is one of the most serious mental disorders affecting modern human life and is often caused by chronic stress. Dopamine system dysfunction is proposed to contribute to the pathophysiology of chronic stress, especially the ventral tegmental area (VTA) which mainly consists of dopaminergic neurons. Focused ultrasound stimulation (FUS) is a promising neuromodulation modality and multiple studies have demonstrated effective ultrasonic activation of cortical, subcortical, and related networks. However, the effects of FUS on the dopamine system and the potential link to chronic stress-induced depressive behaviors are relatively unknown. Here, we measured the effects of FUS targeting VTA on the improvement of depression-like behavior and evaluated the dopamine concentration in the downstream region - medial prefrontal cortex (mPFC). We found that targeting VTA FUS treatment alleviated chronic restraint stress (CRS) -induced anhedonia and despair behavior. Using an in vivo photometry approach, we analyzed the dopamine signal of mPFC and revealed a significant increase following the FUS, positively associated with the improvement of anhedonia behavior. FUS also protected the dopaminergic neurons in VTA from the damage caused by CRS exposure. Thus, these results demonstrated that targeting VTA FUS treatment significantly rescued the depressive-like behavior and declined dopamine level of mPFC induced by CRS. These beneficial effects of FUS might be due to protection in the DA neuron of VTA. Our findings suggest that FUS treatment could serve as a new therapeutic strategy for the treatment of stress-related disorders.

Social excluder's face reduces gaze-triggered attention orienting.

Social ostracism, a negative affective experience in interpersonal interactions, is thought to modulate the gaze-cueing effect (GCE). However, it is unclear whether the impact of social exclusion on the GCE is related to the identity of the cueing face. Therefore, the present study employed a two-phase paradigm to address this issue. In the first phase, two groups of participants were instructed to complete a Cyberball game with two virtual avatars to establish a binding relationship between a specific face's identity and the emotions of social exclusion or inclusion. In the second phase, these two virtual avatars (exclusion faces/inclusion faces) and two new faces (control faces) were used as cueing faces in the gaze-cueing task. The results found that, for the exclusion group, the magnitudes of the GCEs for the exclusion and exclusion-control faces were similar in the 200 ms stimulus onset asynchrony (SOA) condition, while the exclusion face's GCE was significantly smaller than that of the exclusion-control face in the 700 ms SOA condition. In contrast, for the inclusion group, the GCEs for inclusion and inclusion-control faces in both the 200 ms SOA and 700 ms SOA conditions did not significantly differ. This study reveals that the effect of social exclusion on the GCE is related to the identity of the cueing face, with individuals more reluctant to follow the gaze direction of excluder and shift their attention and provides experimental evidence that the perception of higher social relations can exert a top-down impact on the processing of social spatial cues.

Event-related potential evidence for tactile orientation processing in the human brain.

It is well known that information on stimulus orientation plays an important role in sensory processing. However, the neural mechanisms underlying somatosensory orientation perception are poorly understood. Adaptation has been widely used as a tool for examining sensitivity to specific features of sensory stimuli. Using the adaptation paradigm, we measured event-related potentials (ERPs) in response to tactile orientation stimuli presented pseudo-randomly to the right-hand palm in trials with all the same or different orientations. Twenty participants were asked to count the tactile orientation stimuli. The results showed that the adaptation-related N60 component was observed around contralateral central-parietal areas, possibly indicating orientation processing in the somatosensory regions. Conversely, the adaptation-related N120 component was identified bilaterally across hemispheres, suggesting the involvement of the frontoparietal circuitry in further tactile orientation processing. P300 component was found across the whole brain in all conditions and was associated with task demands, such as attention and stimulus counting. These findings help provide an understanding of the mechanisms of tactile orientation processing in the human brain.

An Active and Robust Catalytic Architecture of NiCo/GaN Nanowires for Light-Driven Hydrogen Production from Methanol.

On-site hydrogen production from liquid organic hydrogen carriers e.g., methanol provides an emerging strategy for the safe storage and transportation of hydrogen. Herein, a catalytic architecture consisting of nickel-cobalt nanoclusters dispersed on gallium nitride nanowires supported by silicon for light-driven hydrogen production from methanol is reported. By correlative microscopic, spectroscopic characterizations, and density functional theory calculations, it is revealed that NiCo nanoclusters work in synergy with GaN nanowires to enable the achievement of a significantly reduced activation energy of methanol dehydrogenation by switching the potential-limiting step from *CHO → *CO to *CH3 O → *CH2 O. In combination with the marked photothermal effect, a high hydrogen rate of 5.62 mol·gcat-1·h-1 with a prominent turnover frequency of 43,460 h-1 is achieved at 5 Wcm-2 without additional energy input. Remarkably, the synergy between Co and Ni, in combination with the unique surface of GaN, renders the architecture with outstanding resistance to sintering and coking. The architecture thereby exhibits a high turnover number of >16,310,000 over 600 h. Outdoor testing validates the viability of the architecture for active and robust hydrogen evolution under natural concentrated sunlight. Overall, this work presents a promising architecture for on-site hydrogen production from CH3 OH by virtually unlimited solar energy.

Accumulation characteristics of metals in human breast milk and association with dietary intake in northeastern China.

The trace elements present in breast milk play a vital role in the growth and development of infants. Nevertheless, numerous studies have reported the presence of toxic metal contamination in breast milk from various countries and regions, which poses potential risks to breastfed infants. This article aimed to investigate the characteristics of trace elements in breast milk and explore the relationship between breast milk and diet in Dalian, a coastal city in northeastern China. Breast milk samples and representative local food samples were collected from Dalian for research. The results revealed that 57 % of breast milk samples significantly exceeded the WHO safety limit (0.6 µg/L) for arsenic, with a measured mean value of 0.96 µg/L. Moreover, the levels of chromium (mean value: 2.63 µg/L) in 34 % of breast milk samples exceed the WHO recommended safety level (chromium: 1.5 µg/L). Aquatic foods accounted for 60 % to 90 % of the total intake of arsenic, cadmium, vanadium, mercury, and lead. The Spearman correlation analysis demonstrated strong positive correlations among breast milk metal elements, including copper-zinc (r = 0.68) and nickel­chromium (r = 0.89). Furthermore, the food-to-milk accumulation factors (FMAF) of strontium, nickel, arsenic, vanadium, cadmium, and mercury were relatively low (median values <0.005). While the FMAF values for chromium and lead were higher, with median values of 0.038 and 0.07, respectively. The results indicated potential risks of the toxic metal arsenic in breast milk from Dalian, China for breastfed infants. Therefore, continuous monitoring of breast milk for toxic metals and foodborne contamination is necessary.

High-Throughput Screening of Surface Engineered Cyanine Nanodots for Active Transport of Therapeutic Antibodies into Solid Tumor.

The successful delivery of therapeutic biomacromolecules into solid tumor holds great challenge due to their high resistance to penetrate through the complex tumor microenvironments. Here, active-transporting nanoparticles are harnessed to efficiently deliver biomacromolecular drugs into solid tumors through cell transcytosis. A series of molecularly precise cyanine 5-cored polylysine G5 dendrimers (Cy5 nanodots) with different peripheral amino acids (G5-AA) is prepared. The capability of these positively charged nanodots to induce cell endocytosis, exocytosis, and transcytosis is evaluated via fluorescence-based high-throughput screen. The optimized nanodots (G5-R) are conjugated with αPD-L1 (a therapeutic monoclonal antibody binding to programmed-death ligand 1) (αPD-L1-G5-R) to demonstrate the nanoparticle-mediated tumor active transport. The αPD-L1-G5-R can greatly enhance the tumor-penetration capability through adsorption-mediated transcytosis (AMT). The effectiveness of αPD-L1-G5-R is tested in treating mice bearing partially resected CT26 tumors, mimicking the local immunotherapy of residual tumors post-surgery in clinic. The αPD-L1-G5-R embedded in fibrin gel can efficiently mediate tumor cell transcytosis, and deliver αPD-L1 throughout the tumor, thereby enhancing immune checkpoint blockade, reducing tumor recurrence, and significantly prolonging the survival time. The active-transporting nanodots are promising platforms for efficient tumor delivery of therapeutic biomacromolecules.

Animal models of hepatitis E infection: Advances and challenges.

Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis worldwide. Although most of HEV infections are asymptomatic, some patients will develop the symptoms, especially pregnant women, the elderly, and patients with preexisting liver diseases, who often experience anorexia, nausea, vomiting, malaise, abdominal pain, and jaundice. HEV infection may become chronic in immunosuppressed individuals. In addition, HEV infection can also cause several extrahepatic manifestations. HEV exists in a wide range of hosts in nature and can be transmitted across species. Hence, animals susceptible to HEV can be used as models. The establishment of animal models is of great significance for studying HEV transmission, clinical symptoms, extrahepatic manifestations, and therapeutic strategies, which will help us understand the pathogenesis, prevention, and treatment of hepatitis E. This review summarized the animal models of HEV, including pigs, monkeys, rabbits, mice, rats, and other animals. For each animal species, we provided a concise summary of the HEV genotypes that they can be infected with, the cross-species transmission pathways, as well as their role in studying extrahepatic manifestations, prevention, and treatment of HEV infection. The advantages and disadvantages of these animal models were also emphasized. This review offers new perspectives to enhance the current understanding of the research landscape surrounding HEV animal models.

Study on brain damage patterns of COVID-19 patients based on EEG signals.

Objective: The coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by the SARA-CoV-2, characterized by high infectivity and incidence. Clinical data indicates that COVID-19 significantly damages patients' perception, motor function, and cognitive function. However, the electrophysiological mechanism by which the disease affects the patient's nervous system is not yet clear. Our aim is to investigate the abnormal levels of brain activity and changes in brain functional connectivity network in patients with COVID-19. Methods: We compared and analyzed electroencephalography signal sample entropy, energy spectrum, and brain network characteristic parameters in the delta (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and beta (13-30 Hz) bands of 15 patients with COVID-19 and 15 healthy controls at rest. Results: At rest, energy values of the four frequency bands in the frontal and temporal lobes of COVID-19 patients were significantly reduced. At the same time, the sample entropy value of the delta band in COVID-19 patients was significantly increased, while the value of the beta band was significantly decreased. However, the average value of the directed transfer function of patients did not show any abnormalities under the four frequency bands. Furthermore, node degree in the temporal lobe of patients was significantly increased, while the input degree of the frontal and temporal lobes was significantly decreased, and the output degree of the frontal and occipital lobes was significantly increased. Conclusion: The level of brain activity in COVID-19 patients at rest is reduced, and the brain functional network undergoes a rearrangement. These results preliminarily demonstrate that COVID-19 patients exhibit certain brain abnormalities during rest, it is feasible to explore the neurophysiological mechanism of COVID-19's impact on the nervous system by using EEG signals, which can provide a certain technical basis for the subsequent diagnosis and evaluation of COVID-19 using artificial intelligence and the prevention of brain nervous system diseases after COVID-19 infection.

Changes in Multiparametric Magnetic Resonance Imaging and Plasma Amyloid-Beta Protein in Subjective Cognitive Decline.

The association between plasma amyloid-beta protein (Aß) and subjective cognitive decline (SCD) remains controversial. We aimed to explore the correlation between neuroimaging findings, plasma Aß, and neuropsychological scales using data from 53 SCD patients and 46 age- and sex-matched healthy controls (HCs). Magnetic resonance imaging (MRI) was used to obtain neuroimaging data for a whole-brain voxel-based morphometry analysis and cortical functional network topological features. The SCD group had slightly lower Montreal Cognitive Assessment (MoCA) scores than the HC group. The Aß42 levels were significantly higher in the SCD group than in the HC group (p < 0.05). The SCD patients demonstrated reduced volumes in the left hippocampus, right rectal gyrus (REC.R), and right precentral gyrus (PreCG.R); an increased percentage fluctuation in the left thalamus (PerAF); and lower average small-world coefficient (aSigma) and average global efficiency (aEg) values. Correlation analyses with Aß and neuropsychological scales revealed significant positive correlations between the volumes of the HIP.L, REC.R, PreCG.R, and MoCA scores. The HIP.L volume and Aß42 were negatively correlated, as were the REC.R volume and Aß42/40. PerAF and aSigma were negatively and positively correlated with the MoCA scores, respectively. The aEg was positively correlated with Aß42/40. SCD patients may exhibit alterations in plasma biomarkers and multi-parameter MRI that resemble those observed in Alzheimer's disease, offering a theoretical foundation for early clinical intervention in SCD.