Graphene/silicon heterojunction for reconfigurable phase-relevant activation function in coherent optical neural networks

Optical neural networks (ONNs) herald a new era in information and communication technologies and have implemented various intelligent applications. In an ONN, the activation function (AF) is a crucial component determining the network performances and on-chip AF devices are still in development. Here, we first demonstrate on-chip reconfigurable AF devices with phase activation fulfilled by dual-functional graphene/silicon (Gra/Si) heterojunctions. With optical modulation and detection in one device, time delays are shorter, energy consumption is lower, reconfigurability is higher and the device footprint is smaller than other on-chip AF strategies. The experimental modulation voltage (power) of our Gra/Si heterojunction achieves as low as 1 V (0.5 mW), superior to many pure silicon counterparts. In the photodetection aspect, a high responsivity of over 200 mA/W is realized. Special nonlinear functions generated are fed into a complex-valued ONN to challenge handwritten letters and image recognition tasks, showing improved accuracy and potential of high-efficient, all-component-integration on-chip ONN. Our results offer new insights for on-chip ONN devices and pave the way to high-performance integrated optoelectronic computing circuits

Single-cell RNA sequencing reveals cell subpopulations in the tumor microenvironment contributing to hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is among the deadliest cancers worldwide, and advanced HCC is difficult to treat. Identifying specific cell subpopulations in the tumor microenvironment and exploring interactions between the cells and their environment are crucial for understanding the development, prognosis, and treatment of tumors.Methods: In this study, we constructed a tumor ecological landscape of 14 patients with HCC from 43 tumor tissue samples and 14 adjacent control samples. We used bioinformatics analysis to reveal cell subpopulations with potentially specific functions in the tumor microenvironment and to explore the interactions between tumor cells and the tumor microenvironment.Results: Immune cell infiltration was evident in the tumor tissues, and BTG1+RGS1+ central memory T cells (Tcms) interact with tumor cells through CCL5-SDC4/1 axis. HSPA1B may be associated with remodeling of the tumor ecological niche in HCC. Cancer-associated fibroblasts (CAFs) and macrophages (TAMs) were closely associated with tumor cells. APOC1+SPP1+ TAM secretes SPP1, which binds to ITGF1 secreted by CAFs to remodel the tumor microenvironment. More interestingly, FAP+ CAF interacts with naïve T cells via the CXCL12–CXCR4 axis, which may lead to resistance to immune checkpoint inhibitor therapy.Conclusion: Our study suggests the presence of tumor cells with drug-resistant potential in the HCC microenvironment. Among non-tumor cells, high NDUFA4L2 expression in fibroblasts may promote tumor progression, while high HSPA1B expression in central memory T cells may exert anti-tumor effects. In addition, the CCL5–SDC4/1 interaction between BTG1+RGS1+ Tcms and tumor cells may promote tumor progression. Focusing on the roles of CAFs and TAMs, which are closely related to tumor cells, in tumors would be beneficial to the progress of systemic therapy research

Missing WD40 Repeats in ATG16L1 Delays Canonical Autophagy and Inhibits Noncanonical Autophagy

Canonical autophagy is an evolutionarily conserved process that forms double-membrane structures and mediates the degradation of long-lived proteins (LLPs). Noncanonical autophagy (NCA) is an important alternative pathway involving the formation of microtubule-associated protein 1 light chain 3 (LC3)-positive structures that are independent of partial core autophagy proteins. NCA has been defined by the conjugation of ATG8s to single membranes (CASM). During canonical autophagy and NCA/CASM, LC3 undergoes a lipidation modification, and ATG16L1 is a crucial protein in this process. Previous studies have reported that the WDR domain of ATG16L1 is not necessary for canonical autophagy. However, our study found that WDR domain deficiency significantly impaired LLP degradation in basal conditions and slowed down LC3-II accumulation in canonical autophagy. We further demonstrated that the observed effect was due to a reduced interaction between ATG16L1 and FIP200/WIPI2, without affecting lysosome function or fusion. Furthermore, we also found that the WDR domain of ATG16L1 is crucial for chemical-induced NCA/CASM. The results showed that removing the WDR domain or introducing the K490A mutation in ATG16L1 significantly inhibited the NCA/CASM, which interrupted the V-ATPase-ATG16L1 axis. In conclusion, this study highlights the significance of the WDR domain of ATG16L1 for both canonical autophagy and NCA functions, improving our understanding of its role in autophagy

MiR-181c-5p ameliorates learning and memory in sleep-deprived mice via HMGB1/TLR4/NF-κB pathway

Abstract Sleep deprivation (SD) can lead to cognitive impairment caused by neuroinflammation. MiR-181c-5p/HMGB1 axis plays a part in anti-inflammation effects. However, the mechanism that miR-181c-5p facilitates learning and memory in SD mice remains unclear. So we investigated the role of miR-181c-5p in learning and memory impairment induced by SD. We overexpressed miR-181c-5p in the mice hippocampus by injecting lentivirus vector-miR-181c-5p (LV-miR-181c-5p) particles. Mice were divided into four groups: control (Ctrl), SD, SD + miR-181c-5p and SD + vector. We found that mice in the third group showed ameliorated learning and memory compared with the fourth group. The content of ionized calcium binding adaptor molecule 1 (IBA-1) in the third group was decreased compared with the fourth group. Moreover, the expression levels of HMGB1, TLR4 and p-NF-κB in the hippocampus of overexpressed miR-181c-5p mice were reduced. In total, miR-181c-5p ameliorated learning and memory in SD mice via the HMGB1/TLR4/NF-κB pathway

Acupuncture Decreases NF-κB p65, miR-155, and miR-21 and Increases miR-146a Expression in Chronic Atrophic Gastritis Rats

Acupuncture has been used to treat chronic atrophic gastritis (CAG) in traditional Chinese medicine (TCM) for centuries. In this study, we evaluated the effect of acupuncture at Zusanli (ST36), Zhongwan (CV12), and Pishu (BL20) acupoints on weight changes of rats, histological changes of gastric glands, and expressions changes of nuclear factor-kappa B (NF-κB) p65, microRNA- (miR-) 155, miR-21, and miR-146a in CAG rats induced by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) combined with irregular diet. Consequently, we found that acupuncture treatment elevated body weight of rats significantly when compared to the model group. By observing histological changes, we found that the acupuncture group showed better improvement of gastric mucosa injury than the model group. Our results also demonstrated upregulation of NF-κB p65, miR-155, and miR-21 in gastric tissue of CAG rats and a positive correlation between miR-155 and miR-21. Relatively, expression of miR-146a was downregulated and negative correlation relationships between miR-146a and miR-155/miR-21 in CAG rats were observed. Additionally, expressions of NF-κB p65, miR-155, and miR-21 were downregulated and miR-146a was upregulated after acupuncture treatment. Taken together, our data imply that acupuncture can downregulate NF-κB p65, miR-155, and miR-21 and upregulate miR-146a expression in CAG rats. NF-κB p65, miR-155, miR-21, and miR-146a may play important roles in therapeutic effect of acupuncture in treating CAG

Electroacupuncture Improves Antidepressant Effects in CUMS Rats by Protecting Hippocampal Synapse and Mitochondrion: An Ultrastructural and iTRAQ Proteomic Study

Electroacupuncture (EA) is considered a complementary therapy for depression. Trials also found that EA has additive benefits when combined with medication compared with medication alone. It is revealed that EA restores altered hippocampal synaptic plasticity in depressed brain. But precise molecular mechanism is poorly understood. Here, we evaluated the therapeutic effects of EA and EA combined with selective serotonin reuptake inhibitor (SSRI) on depressed (CUMS) rats. Then a new proteomics approach, isobaric tag for relative and absolute quantitation (iTRAQ), was used to explore the differential expressed synaptic protein in hippocampus between CUMS and EA-treated rats to identify the possible target molecular mechanism of its effects. We found that EA had additive benefit against depressive behaviors when combined with SSRI. Ultrastructure study on neuron showed significant change in postsynapse density (PSD) and mitochondrion. Through iTRAQ, it is found that synaptic and mitochondrial proteins were significantly changed after EA, consisting with ultrastructure study results. These findings suggest that EA improves antidepressant performance in depressed rats through protecting synaptic and mitochondrial functions in hippocampus

iTRAQ-Based Protein Profiling in CUMS Rats Provides Insights into Hippocampal Ribosome Lesion and Ras Protein Changes Underlying Synaptic Plasticity in Depression

Hippocampal atrophy is one of the key changes in the brain implicated in the biology of depression. However, the precise molecular mechanism remains poorly understood due to a lack of biomarkers. In this research, we used behavioral experiments to evaluate anxiety and anhedonia levels in depressed rats using chronic unpredictable mild stress (CUMS) modeling. We also used isobaric tag for relative and absolute quantitation (iTRAQ) to identify the differentially expressed hippocampal proteins between depressed and normal rats. Bioinformatics analyses were also performed for a better understanding. The results showed that CUMS rats had higher anxiety and anhedonia levels than control rats, along with hippocampal lesions. Through iTRAQ and bioinformatics analyses, we found that ribosome proteins were significantly downregulated and Ras proteins exhibited a mixed change in the hippocampus of depressed rats. These findings suggest that the expression of hippocampal ribosome lesions and Ras proteins is significantly different in depressed rats than in control rats, providing new insights into the neurobiology of depression

Unusual KIE and Dynamics Effects in the Fe-catalyzed Hetero-Diels-Alder Reaction of Unactivated Aldehydes and Dienes

Hetero-Diels-Alder (HDA) reaction is an important synthetic method for many natural products. An iron(III) catalyst was developed to catalyze the challenging HDA reaction of unactivated aldehydes and dienes with high selectivity. Here we report extensive density-functional theory (DFT) calculations and molecular dynamics simulations that show effects of iron (including its coordinate mode and/or spin state) on the dynamics of this reaction: considerably enhancing dynamically stepwise process, broadening entrance channel and narrowing exit channel from concerted asynchronous transition states. Also, our combined computational and experimental secondary KIE studies reveal unexpectedly large KIE values for the five-coordinate pathway even with considerable C-C bond forming, due to equilibrium isotope effect from the change in the metal coordination. Moreover, steric and electronic effects are computationally shown to dictate the C=O chemoselectivity for an α,β-unsaturated aldehyde, which is verified experimentally. Our mechanistic study may help design homogeneous, heterogeneous and biological catalysts for this challenging reaction.status: publishe