PbS/CsPbBr3 Heterojunction for Broadband Neuromorphic Vision Sensing.

Neuromorphic light sensors with analogue-domain image processing capability hold promise for overcoming the energy efficiency limitations and latency of von Neumann architecture-based vision chips. Recently, metal halide perovskites, with strong light-matter interaction, long carrier diffusion length, and exceptional photoelectric conversion efficiencies, exhibit reconfigurable photoresponsivity due to their intrinsic ion migration effect, which is expected to advance the development of visual sensors. However, suffering from a large bandgap, it is challenging to achieve highly tunable responsivity simultaneously with a wide-spectrum response in perovskites, which will significantly enhance the image recognition accuracy through the machine learning algorithm. Herein, we demonstrate a broadband neuromorphic visual sensor from visible (Vis) to near-infrared (NIR) by coupling all-inorganic metal halide perovskites (CsPbBr3) with narrow-bandgap lead sulfide (PbS). The PbS/CsPbBr3 heterostructure is composed of high-quality single crystals of PbS and CsPbBr3. Interestingly, the ion migration of CsPbBr3 with the implementation of an electric field induces the energy band dynamic bending at the interface of the PbS/CsPbBr3 heterojunction, leading to reversible, multilevel, and linearly tunable photoresponsivity. Furthermore, the reconfigurable and broadband photoresponse in the PbS/CsPbBr3 heterojunction allows convolutional neuronal network processing for pattern recognition and edge enhancements from the Vis to the NIR waveband, suggesting the great potential of the PbS/CsPbBr3 heterostructure in artificial intelligent vision sensing.

10-year Temporal Trends of Intravenous Thrombolysis in Acute Ischemic Stroke: Analysis of the China National Stroke Registry I-â ¢.

OBJECTIVES: To investigate the 10-year trend in healthcare quality of intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator in acute ischemic stroke (AIS) in China. MATERIALS AND METHODS: We analyzed 42,188 AIS within 7 days of onset from the China National Stroke Registry (CNSR) Ⅰ-Ⅲ. Primary outcomes were temporal changes in the proportion of patients arriving at the hospital within 3.5 hours (and 2 hours) of onset and receiving IVT within 4.5 hours (and 3 hours), stratified by region and hospital tier. Secondary outcomes included temporal changes in door-to-needle time (DNT), DNT ≤60 min and favorable outcome defined as a 90-day modified Rankin Scale (mRS) of 0-1. RESULTS: Among patients arriving at the hospital within 3.5 hours of onset, 13.5%, 7.1% and 33.4% patients received IVT within 4.5 hours in CNSR Ⅰ, Ⅱ and Ⅲ, respectively, including a higher proportion from eastern China (37.0%) and tertiary hospitals (36.5%). The median DNT was shorter in CNSR Ⅲ (60.0 min) than those in Ⅱ (95.0 min) and I (94.0 min). The proportion of patients with DNT ≤60 min was greater in Ⅲ (53.4%) than those in Ⅱ (26.7%) and Ⅰ (13.4%). The proportion of favorable outcomes was higher in CNSR Ⅲ (72.8%) than those in Ⅱ (49.6%) and Ⅰ (49.4%). Similar trends were observed for patients arriving at the hospital within 2 hours and receiving IVT within 3 hours of onset. CONCLUSIONS: The healthcare quality of IVT has improved remarkably in the past decade, notably in eastern China and tertiary hospitals.

White matter abnormalities are associated with the declined ability of reasoning and problem-solving in major depressive disorder.

OBJECTIVES: Executive function in people with depression is linked to the integrity of white matter fibers in the brain. We hypothesized that the maze tests in neuropsychological tests assessed reasoning and problem-solving abilities dependent on the integrity of brain white matter fibers, and assessed this relationship using diffusion tensor imaging (DTI) in depressed patients and healthy controls. METHODS: Participants aged from 18 to 50 years were recruited from Zhumadian Second People's Hospital from July 2018 to August 2019. The sample included 33 clinically diagnosed individuals with major depressive disorder (MDD) and 24 healthy volunteers (HVs). All subjects underwent Neuropsychological assessment battery (NAB) maze tests and DTI. Tract-based spatial statistics technology in FSL software was used to process DTI data, and threshold-free cluster enhancement (TFCE) was used to perform multiple comparison corrections. The fractional anisotropy (FA) of white matter fibers in the MDD group and HVs group were compared and extracted. Pearson correlation was used to analyze the relationship between FA and NAB scores and HAMD scores. RESULTS: The mean NAB maze test score for the MDD group was lower than the HVs group, and the difference was statistically significant (F = 11.265, p = .037). The FA value of the body of corpus callosum and cerebral peduncle right in the depression group was lower than that in the healthy control group, and the difference was statistically significant (p < .05). FA value of the body of corpus callosum was positively correlated with NAB score (r = 0.400, p = .036), but not with the HAMD score (r = 0.065, p = .723). CONCLUSIONS: The decreased ability of reasoning and problem-solving in MDD may be due to the decreased integrity of the white matter fibers of the body of the corpus callosum.

Analysis of the rule of window-to-wall ratio on energy demand of residential buildings in different locations in China.

Building energy demands are influenced by the window-to-wall ratio (WWR). The impact of the WWR on the energy demand in the same area has been researched by software. However, the impact of the WWR on the energy demand of buildings in different locations of China has not been investigated using the energy balance equation. The equation for the indoor temperature variation under various internal and external disturbances was provided in this study. The relationship between parameters A and B and the change in indoor temperature was proven. China's Harbin, Beijing, and Chengdu air-conditioning and heating loads, as well as the impact of changing WWR on the rate of energy savings for air-conditioning and heating energy demand, were studied. After investigating the changes in the cooling and heating loads in various cities under various WWRs, the suitable relationship between the cooling and heating loads and the WWR of three urban units was discovered. The findings indicated that despite the three cities' various climates and the diverse energy demands for air conditioning and heating in each city, with the same change in the WWR of urban buildings, the change rate of the air conditioning and heating loads in each city was near. Meanwhile, the heating and cooling loads were linear with WWR.

Identifying the difference in time perception between major depressive disorder and bipolar depression through a temporal bisection task.

BACKGROUND: It is difficult to make a precise diagnosis to distinguish patients with Major Depressive Disorder (MDD) from patients with Bipolar Depressive Disorder (current depressive episode, BD). This study will explore the difference in time perception between MDD and BD using a temporal bisection task. METHODS: In this temporal bisection task, 30 MDD patients, 30 BD patients, and 30 healthy controls (HC) had to categorize a signal duration, between 400 and 1600 milliseconds (ms), as either short or long. A repeated measurement analysis of variance with 3 (subject type) × 7 (time interval) was performed on the long response ratio with Bonferroni correction for multiple comparisons. Origin software was used to calculate the subjective bisection point (BP), difference limen (DL), and Weber ratio (WR). The Hamilton Depression Rating Scale for depression-17 was used to assess depressive symptoms in the patients. RESULTS: The data showed that the interaction effect between subject type and duration was significant (F (6,498) = 4.656, p <0.001, η2p = 0.101). At 400 ms, and the long response of the MDD group was greater than HC group (p<0.017, Bonferroni-corrected). At 1200, 1400 and 1600 ms, the long response of BD group is smaller than HC group, (p<0.017, Bonferroni-corrected). The one-way ANOVA revealed significant difference among the HC, MDD and BD groups in the BP values WR values, F(2, 81) = 3.462, p = 0.036 vs. F(2, 81) = 3.311, p = 0.042. Post-hoc tests showed that the value of BP in the MDD group was less than BD group (p = 0.027) and the value of BP in the MDD group was less than HC group (p = 0.027), while there was not significant difference of BP values between BD group and HC group. The WR values in MDD group larger than the HC group (p = 0.022). LIMITATIONS: Severity of depression not divided and analyzed according to the Hamilton Depression Rating Scale score. CONCLUSION: The time perception of the MDD and BD groups was different from that of the HC group, they overestimated short time periods. Compared with the BD group, the MDD group had a smaller time bisector, and these patients felt that time passed more slowly. The time sensitivity of MDD group and BD group were less than the HC group. However, there was no statistical difference in time sensitivity between the MDD and BD groups.

HRD1-mediated METTL14 degradation regulates m6A mRNA modification to suppress ER proteotoxic liver disease.

Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) lumen triggers an unfolded protein response (UPR) for stress adaptation, the failure of which induces cell apoptosis and tissue/organ damage. The molecular switches underlying how the UPR selects for stress adaptation over apoptosis remain unknown. Here, we discovered that accumulation of unfolded/misfolded proteins selectively induces N6-adenosine-methyltransferase-14 (METTL14) expression. METTL14 promotes C/EBP-homologous protein (CHOP) mRNA decay through its 3' UTR N6-methyladenosine (m6A) to inhibit its downstream pro-apoptotic target gene expression. UPR induces METTL14 expression by competing against the HRD1-ER-associated degradation (ERAD) machinery to block METTL14 ubiquitination and degradation. Therefore, mice with liver-specific METTL14 deletion are highly susceptible to both acute pharmacological and alpha-1 antitrypsin (AAT) deficiency-induced ER proteotoxic stress and liver injury. Further hepatic CHOP deletion protects METTL14 knockout mice from ER-stress-induced liver damage. Our study reveals a crosstalk between ER stress and mRNA m6A modification pathways, termed the ERm6A pathway, for ER stress adaptation to proteotoxicity.

Facial Expression Recognition and ReHo Analysis in Major Depressive Disorder.

Objective: To explore the characteristics of expression recognition and spontaneous activity of the resting state brain in major depressive disorder (MDD) patients to find the neural basis of expression recognition and emotional processing. Methods: In this study, two of the six facial expressions (happiness, sadness, anger, fear, aversion, and surprise) were presented in quick succession using a short expression recognition test. The differences in facial expression recognition between MDD patients and healthy people were compared. Further, the differences in ReHo values between the two groups were compared using a resting-state functional magnetic resonance imaging (fMRI) scan to investigate the characteristics of spontaneous brain activity in the resting state and its relationship with clinical symptoms and the accuracy of facial expression recognition in patients with MDD. Results: (1) The accuracy of facial expression recognition in patients with MDD was lower than that of the HC group. There were differences in facial expression recognition between the two groups in sadness-anger (p = 0.026), surprise-aversion (p = 0.038), surprise-happiness (p = 0.014), surprise-sadness (p = 0.019), fear-happiness (p = 0.027), and fear-anger (p = 0.009). The reaction time for facial expression recognition in the patient group was significantly longer than that of the HC group. (2) Compared with the HC group, the ReHo values decreased in the left parahippocampal gyrus, left thalamus, right putamen, left putamen, and right angular gyrus, and increased in the left superior frontal gyrus, left middle temporal gyrus, left medial superior frontal gyrus, and right medial superior frontal gyrus in the patient group. (3) Spearman correlation analysis showed no statistical correlation between ReHo and HAMD-17 scores in MDD patients (p > 0.05). The ReHo value of the left putamen was negatively correlated with the recognition of fear-surprise (r = -0.429, p = 0.016), the ReHo value of the right angular gyrus was positively correlated with the recognition of sadness-anger (r = 0.367, p = 0.042), and the ReHo value of the right medial superior frontal gyrus was negatively correlated with the recognition of fear-anger (r = -0.377, p = 0.037). Conclusion: In view of the different performance of patients with MDD in facial expression tasks, facial expression recognition may have some suggestive effect on the diagnosis of depression and has clinical guiding significance. Many brain regions, including the frontal lobe, temporal lobe, striatum, hippocampus, and thalamus, in patients with MDD show extensive ReHo abnormalities in the resting state. These brain regions with abnormal spontaneous neural activity are important components of LCSPT and LTC circuits, and their dysfunctional functions cause disorder of emotion regulation. The changes in spontaneous activity in the left putamen, right angular gyrus, and right medial superior frontal gyrus may represent the abnormal pattern of spontaneous brain activity in the neural circuits related to emotion perception and may be the neural basis of facial expression recognition.

The cGAS-STING pathway: The role of self-DNA sensing in inflammatory lung disease.

The presence of DNA in the cytosol is usually a sign of microbial infections, which alerts the host innate immune system to mount a defense response. Cyclic GMP-AMP synthase (cGAS) is a critical cytosolic DNA sensor that elicits robust innate immune responses through the production of the second messenger, cyclic GMP-AMP (cGAMP), which binds and activates stimulator of interferon genes (STING). However, cGAS binds to DNA irrespective of DNA sequence, therefore, self-DNA leaked from the nucleus or mitochondria can also serve as a cGAS ligand to activate this pathway and trigger extensive inflammatory responses. Dysregulation of the cGAS-STING pathway is responsible for a broad array of inflammatory and autoimmune diseases. Recently, evidence has shown that self-DNA release and cGAS-STING pathway over-activation can drive lung disease, making this pathway a promising therapeutic target for inflammatory lung disease. Here, we review recent advances on the cGAS-STING pathway governing self-DNA sensing, highlighting its role in pulmonary disease.

Age-Dependent Differences in T-Cell Responses to Influenza A Virus.

Respiratory infections from influenza A virus (IAV) cause substantial morbidity and mortality in children relative to adults. T cells play a critical role in the host response to IAV by supporting the innate and humoral responses, mediating cytotoxic activity, and promoting recovery. There are age-dependent differences in the number, subsets, and localization of T cells, which impact the host response to pathogens. In this article, we first review how T cells recognize IAV and examine differences in the resting T-cell populations between juveniles and adults. Next, we describe how the juvenile CD4+, CD8+, and regulatory T-cell responses compare with those in adults and discuss the potential physiologic and clinical consequences of the differences. Finally, we explore the roles of two unconventional T-cell types in the juvenile response to influenza, natural-killer T cells and γδ T cells. A clear understanding of age-dependent differences in the T-cell response is essential to developing therapies to prevent or reverse the deleterious effects of IAV in children.

Metabolic and non-metabolic liver zonation is established non-synchronously and requires sinusoidal Wnts.

The distribution of complementary metabolic functions in hepatocytes along a portocentral axis is called liver zonation. Endothelial secreted Wnt ligands maintain metabolic zonation in the adult murine liver but whether those ligands are necessary to initiate zonation in the immature liver has been only partially explored. Also, numerous non-metabolic proteins display zonated expression in the adult liver but it is not entirely clear if their localization requires endothelial Wnts. Here we used a novel transgenic mouse model to compare the spatial distribution of zonated non-metabolic proteins with that of typical zonated metabolic enzymes during liver maturation and after acute injury induced by carbon tetrachloride (CCl4). We also investigated how preventing Wnt ligand secretion from endothelial cells affects zonation patterns under homeostasis and after acute injury. Our study demonstrates that metabolic and non-metabolic zonation are established non-synchronously during maturation and regeneration and require multiple endothelial Wnt sources.

Influence of gene modification in biological behaviors and responses of mouse lung telocytes to inflammation.

BACKGROUND: Telocytes play key roles in maintenance of organ/tissue function and prevention of organ injury. However, there are great challenges to investigate telocytes functions using primary telocytes, due to the difficulties of isolation, identification, and stability. The present study aims at constructing continuous cell strain of mouse lung telocyte cell line with stable characters by gene modification and investigating biological behaviors and responses of gene-modified telocytes to inflammation. METHODS: Mouse primary lung telocytes were isolated and identified using immune-labeling markers and immunoelectron microscopy. Primary telocytes were transformed with Simian vacuolating virus 40 small and large T antigen (SV40). Biological characters, behaviors morphology, and proliferation of those gene-modified telocytes were defined and monitored dynamically for 50 generations, as compared with primary lung telocytes. Cell cycle of mouse primary lung telocytes or gene-modified telocytes was detected by flow cytometry. RESULTS: Gene modified telocytes of generations 5, 10, 30 and 50 were observed with telopodes and also showed CD34 and ckit positive. Multiple cellular morphology were also observed on telocyte cell-line under monitor of celliq and enhanced cell proliferation were showed. SV40 transduction was also reduced apoptosis and increased the ratio of S and G2 phases in telocyte cell-line. CONCLUSION: We successfully constructed mouse lung telocyte cell-line which maintained the biological properties and behaviors as primary telocytes and could responses to inflammation induced by LPS. Thus, gene-modified lung telocytes, Telocyte Line, would provide a cell tool for researchers exploring the roles and applications of telocytes involved in physiological and pathological states in future.

Inhibition of connexin 43 hemichannels improves postoperative cognitive function in aged mice.

AIMS: Postoperative cognitive dysfunction (POCD) is a neurological disorder associated with neuroinflammation. Connexin 43 (Cx43), an essential component of gap junction, plays a crucial role in neuroinflammation. The present study was designed to investigate the role of Cx43 in the process of POCD. METHODS: POCD model was established in aged mice with internal fixation of tibial fractures. Cognitive function was examined using the Morris water maze test. Hippocampus was collected for reverse transcription polymerase chain reaction (RT-PCR), western blotting, and immunofluorescence assays. RESULTS: In the water maze test, mice undergoing surgery took longer time to reach target platform than the controls. IL-1ß and TNF-α mRNA expressions in the hippocampus were significantly increased in surgery mice. Cx43 protein presence in the hippocampus was increased in the surgery group. Treatment of Gap26, a specific blocker of Cx43 hemichannel, reduced the Cx43 protein presence, decreased mRNA expressions of IL-1ß and TNF-α, and improved cognitive score in the maze test. CONCLUSION: Internal fixation of tibial fractures in aged mice induces Cx43 hemichannels opening and enhances neuroinflammation in the hippocampus, leading to cognitive impairment. Administration of Gap26 reduces neuroinflammation in the hippocampus and improves postoperative cognitive function.

Telocytes promote VEGF expression and alleviate ventilator-induced lung injury in mice.

Mechanical ventilation (MV) is an important procedure for the treatment of patients with acute lung injury or acute respiratory distress syndrome in a clinical setting; however, MV can lead to severe complications, including ventilator-induced lung injury (VILI). Telocytes (TCs) can promote tissue repair following injury in the heart, kidneys, and other organs. The aim of this study was to investigate the role of TCs in VILI in mice and the associated mechanisms. By using in vivo studies in mice and in vitro studies in cells, we demonstrated that an airway injection of TCs can reduce the pulmonary inflammatory response and improve the lung function in mice with VILI and promote the proliferation of pulmonary vascular endothelial cells. We also demonstrated that the impact of TCs on VILI repair might partially due to vascular endothelial growth factor (VEGF) secreted by TCs upon VILI stimulation, and that VEGF could induce the proliferation of hemangioendothelioma endothelial cells (EOMA). Collectively, our results revealed novel functions of TCs in VILA repair and shed light on the complications that are caused by MV.

A Pck1-directed glycogen metabolic program regulates formation and maintenance of memory CD8+ T cells.

CD8+ memory T (Tm) cells are fundamental for protective immunity against infections and cancers 1-5 . Metabolic activities are crucial in controlling memory T-cell homeostasis, but mechanisms linking metabolic signals to memory formation and survival remain elusive. Here we show that CD8+ Tm cells markedly upregulate cytosolic phosphoenolpyruvate carboxykinase (Pck1), the hub molecule regulating glycolysis, tricarboxylic acid cycle and gluconeogenesis, to increase glycogenesis via gluconeogenesis. The resultant glycogen is then channelled to glycogenolysis to generate glucose-6-phosphate and the subsequent pentose phosphate pathway (PPP) that generates abundant NADPH, ensuring high levels of reduced glutathione in Tm cells. Abrogation of Pck1-glycogen-PPP decreases GSH/GSSG ratios and increases levels of reactive oxygen species (ROS), leading to impairment of CD8+ Tm formation and maintenance. Importantly, this metabolic regulatory mechanism could be readily translated into more efficient T-cell immunotherapy in mouse tumour models.

Lipoxin A4 protects against lipopolysaccharide-induced sepsis by promoting innate response activator B cells generation.

Sepsis is a serious disease that leads to severe inflammation, dysregulation of immune system, multi-organ failure and death. Innate response activator (IRA) B cells, which produce granulocyte-macrophage colony-stimulating factor (GM-CSF), protect against microbial sepsis. Lipid mediator lipoxin A4 (LXA4) exerts anti-inflammatory and immunoregulatory effects, and it has been reported that LXA4 receptor ALX/FPR2 is expressed on B cells. Here, we investigated the potential role of LXA4 on IRA B cells in lipopolysaccharide (LPS)-induced sepsis. We found that LXA4 significantly promoted the expansion of splenic IRA B cells and increased GM-CSF expression in splenic B cells with LPS stimulation. After splenectomy, LXA4 treatment did not change the serum or peritoneal IL-1ß, IL-6 and TNF-α levels in LPS-induced sepsis. LXA4 accelerated the migration of peritoneal B cells to spleen for their differentiation into IRA B cells, whereas this effect was independent of peritoneal macrophage. Furthermore, LXA4 enhanced the phosphorylation level of signal transducer and activator of transcription 5 (STAT5) in splenic B cells. These results suggest that LXA4 protects against LPS-induced sepsis by promoting the generation and migration of splenic IRA B cells, and the underlying molecular mechanism may be related to STAT5 activation. It might provide new insights and therapeutic approaches for treating sepsis.

Reversing drug resistance of soft tumor-repopulating cells by tumor cell-derived chemotherapeutic microparticles.

Developing novel approaches to reverse the drug resistance of tumor-repopulating cells (TRCs) or stem cell-like cancer cells is an urgent clinical need to improve outcomes of cancer patients. Here we show an innovative approach that reverses drug resistance of TRCs using tumor cell-derived microparticles (T-MPs) containing anti-tumor drugs. TRCs, by virtue of being more deformable than differentiated cancer cells, preferentially take up T-MPs that release anti-tumor drugs after entering cells, which in turn lead to death of TRCs. The underlying mechanisms include interfering with drug efflux and promoting nuclear entry of the drugs. Our findings demonstrate the importance of tumor cell softness in uptake of T-MPs and effectiveness of a novel approach in reversing drug resistance of TRCs with promising clinical applications.

Tumor cell-derived microparticles polarize M2 tumor-associated macrophages for tumor progression.

Despite identification of macrophages in tumors (tumor-associated macrophages, TAM) as potential targets for cancer therapy, the origin and function of TAM in the context of malignancy remain poorly characterized. Here, we show that microparticles (MPs), as a by-product, released by tumor cells act as a general mechanism to mediate M2 polarization of TAM. Taking up tumor MPs by macrophages is a very efficient process, which in turn results in the polarization of macrophages into M2 type, not only leading to promoting tumor growth and metastasis but also facilitating cancer stem cell development. Moreover, we demonstrate that the underlying mechanism involves the activation of the cGAS/STING/TBK1/STAT6 pathway by tumor MPs. Finally, in addition to murine tumor MPs, we show that human counterparts also possess consistent effect on human M2 polarization. These findings provide new insights into a critical role of tumor MPs in remodeling of tumor microenvironment and better understanding of the communications between tumors and macrophages.

Delivery of oncolytic adenovirus into the nucleus of tumorigenic cells by tumor microparticles for virotherapy.

Oncolytic viruses have been utilized for the treatment of various cancers. However, delivery of the viral particles to tumor cells remains a major challenge. Microparticles (MP) are vesicle forms of plasma membrane fragments of 0.1-1 µm in size that are shed by cells. We have previously shown the delivery of chemotherapeutic drugs using tumor cell-derived MPs (T-MP). Here we report that T-MPs can be utilized as a unique carrier system to deliver oncolytic adenoviruses to human tumors, leading to highly efficient cytolysis of tumor cells needed for in vivo treatment efficacy. This T-MP-mediated oncolytic virotherapy approach holds multiple advantages, including: 1) delivery of oncolytic adenovirus by T-MPs is able to avoid the antiviral effect of host antibodies; 2) delivery of oncolytic adenovirus by T-MPs is not limited by virus-specific receptor that mediates the entry of virus into tumor cells; 3) T-MPs are apt at delivering oncolytic adenoviruses to the nucleus of tumor cells as well as to stem-like tumor-repopulating cells for the desired purpose of killing them. These findings highlight a novel oncolytic adenovirus delivery system with highly promising clinical applications.