Why Batch Normalization Damage Federated Learning on Non-IID Data?

As a promising distributed learning paradigm, federated learning (FL) involves training deep neural network (DNN) models at the network edge while protecting the privacy of the edge clients. To train a large-scale DNN model, batch normalization (BN) has been regarded as a simple and effective means to accelerate the training and improve the generalization capability. However, recent findings indicate that BN can significantly impair the performance of FL in the presence of non-i.i.d. data. While several FL algorithms have been proposed to address this issue, their performance still falls significantly when compared to the centralized scheme. Furthermore, none of them have provided a theoretical explanation of how the BN damages the FL convergence. In this paper, we present the first convergence analysis to show that under the non-i.i.d. data, the mismatch between the local and global statistical parameters in BN causes the gradient deviation between the local and global models, which, as a result, slows down and biases the FL convergence. In view of this, we develop a new FL algorithm that is tailored to BN, called FedTAN, which is capable of achieving robust FL performance under a variety of data distributions via iterative layer-wise parameter aggregation. Comprehensive experimental results demonstrate the superiority of the proposed FedTAN over existing baselines for training BN-based DNN models

Drosophila TRPA Channel Painless Inhibits Male–Male Courtship Behavior through Modulating Olfactory Sensation

The Drosophila melanogaster TRPA family member painless, expressed in a subset of multidendritic neurons embeding in the larval epidermis, is necessary for larval nociception of noxious heat or mechanical stimuli. However, the function of painless in adult flies remains largely unknown. Here we report that mutation of painless leads to a defect in male–male courtship behavior and alteration in olfaction sensitivity in adult flies. Specific downregulation of the expression of the Painless protein in the olfactory projection neurons (PNs) of the antennal lobes (ALs) resulted in a phenotype resembling that found in painless mutant flies, whereas overexpression of Painless in PNs of painless mutant males suppressed male–male courtship behavior. The downregulation of Painless exclusively during adulthood also resulted in male–male courtship behavior. In addition, mutation of the painless gene in flies caused changes in olfaction, suggesting a role for this gene in olfactory processing. These results indicate that functions of painless in the adult central nervous system of Drosophila include modulation of olfactory processing and inhibition of male–male courtship behavior

RS4651 suppresses lung fibroblast activation via the TGF-β1/SMAD signalling pathway.

ABSTRACT Background Idiopathic pulmonary fibrosis (IPF) is a progressive disease resulting in respiratory failure with no efficient treatment options. We investigated the protective effect of RS4651 on pulmonary fibrosis in mice and the mechanism. Methods Intratracheal injection of bleomycin (BLM) was used to induce pulmonary fibrosis in mice. RS4561 was administered intraperitoneally at different doses. Histopathological changes were observed. The level of alpha-smooth muscle actin (α-SMA) were also tested. In vitro, the proliferation and migratory effects of RS4651 treatment on MRC-5 cells pre-treated with transforming growth factor (TGF-β1) were examined. RNA-sequencing was used to detect differentially expressed target genes. Then, the expression of α-SMA, pSMAD2 and SMAD7 were analysed during RS4651 treatment of MRC-5 cells with or without silencing by SMAD7 siRNA. Results Histopathological staining results showed decreased collagen deposition in RS4651 administered mice. Additionally, a lower level of α-SMA was also observed compared to the BLM group. The results of in vitro studies confirmed that RS4651 can inhibit the proliferation and migration, as well as α-SMA and pSMAD2 expression in MRC-5 cells treated with TGF-β1. RNA-sequencing data identified the target gene SMAD7. We found that RS4651 could upregulate SMAD7 expression and inhibit the proliferation and migration of MRC-5 cells via SMAD7, and RS4651 inhibition of α-SMA and pSMAD2 expression was blocked in SMAD7-siRNA MRC-5 cells. In vivo studies further confirmed that RS4651 could upregulate SMAD7 expression in BLM-induced lung fibrosis in mice. Conclusions Our data suggest that RS4651 alleviates BLM-induced pulmonary fibrosis in mice by inhibiting the TGF-β1/SMAD signalling pathway

Activated mouse CD4+Foxp3−CD4^+Foxp3^− T cells facilitate melanoma metastasis via Qa-1-dependent suppression of NK-cell cytotoxicity

The regulatory activities of mouse $CD^4+Foxp3^+$ T cells on various immune cells, including NK cells, have been well documented. Under some conditions, conventional $CD4^+Foxp3^−$ T cells in the periphery are able to acquire inhibitory function on other T cells, but their roles in controlling innate immune cells are poorly defined. As a potential cellular therapy for cancer, ex vivo activated $CD4^+Foxp3^−$ effector T cells are often infused back in vivo to suppress tumor growth and metastasis. Whether such activated T cells could affect NK-cell control of tumorigenesis is unclear. In the present study, we found that mitogen-activated $CD4^+Foxp3^−$ T cells exhibited potent suppressor function on NK-cell proliferation and cytotoxicity in vitro, and notably facilitated B16 melanoma metastasis in vivo. Suppression of NK cells by activated $CD4^+Foxp3^−$ T cells is cell-cell contact dependent and is mediated by Qa-1:NKG2A interaction, as administration of antibodies blocking either Qa-1 or NKG2A could completely reverse this suppression, and significantly inhibited otherwise facilitated melanoma metastasis. Moreover, activated $CD4^+Foxp3^−$ cells from Qa-1 knockout mice completely lost the suppressor activity on NK cells, and failed to facilitate melanoma metastasis when transferred in vivo. Taken together, our findings indicate that innate anti-tumor response is counter regulated by the activation of adaptive immunity, a phenomenon we term as “activation-induced inhibition”. Thus, the regulatory role of activated $CD4^+Foxp3^−$ T cells in NK-cell activity must be taken into consideration in the future design of cancer therapies

Tuberous Sclerosis Complex With Multiple Organ Tumors: Case Report and Literature Review

Pancreatic neuroendocrine neoplasms (PNEN) are tumors that originate from neuroendocrine cells. Only about 1% patients are related to mutation of tuberous sclerosis complex gene. Here, we reported a rare case with involvement of multiple organs and space-occupying lesions. Initially, the patient was thought to have metastasis of a pancreatic tumor. However, the patient was diagnosed as pancreatic neuroendocrine tumors, liver perivascular epithelioid tumors, splenic hamartoma, and renal angiomyolipoma by pathological examination after surgery. We performed genetic mutation detection to identify that tuberous sclerosis complex 2 gene presented with a heterozygous variant. Tuberous sclerosis often presents with widespread tumors, but it is less common to present with pancreatic neuroendocrine tumors and liver perivascular tumors as highlighted in the case. So we analyzed the relationship between TSC gene mutations and related tumors. And we also reviewed the current molecular mechanisms and treatments for tuberous sclerosis complex

Initialization of nanowire or cluster growth critically controlled by the effective V/III ratio at the early nucleation stage

For self-catalyzed nanowires (NWs), reports on how the catalytic droplet initiates successful NW growth are still lacking, making it difficult to control the yield and often accompanying a high density of clusters. Here, we have performed a systematic study on this issue, which reveals that the effective V/III ratio at the initial growth stage is a critical factor that governs the NW growth yield. To initiate NW growth, the ratio should be high enough to allow the nucleation to extend to the entire contact area between the droplet and substrate, which can elevate the droplet off of the substrate, but it should not be too high in order to keep the droplet. This study also reveals that the cluster growth between NWs is also initiated from large droplets. This study provides a new angle from the growth condition to explain the cluster formation mechanism, which can guide high-yield NW growth

Precise Spatiotemporal Control of Optogenetic Activation Using an Acousto-Optic Device

Light activation and inactivation of neurons by optogenetic techniques has emerged as an important tool for studying neural circuit function. To achieve a high resolution, new methods are being developed to selectively manipulate the activity of individual neurons. Here, we report that the combination of an acousto-optic device (AOD) and single-photon laser was used to achieve rapid and precise spatiotemporal control of light stimulation at multiple points in a neural circuit with millisecond time resolution. The performance of this system in activating ChIEF expressed on HEK 293 cells as well as cultured neurons was first evaluated, and the laser stimulation patterns were optimized. Next, the spatiotemporally selective manipulation of multiple neurons was achieved in a precise manner. Finally, we demonstrated the versatility of this high-resolution method in dissecting neural circuits both in the mouse cortical slice and the Drosophila brain in vivo. Taken together, our results show that the combination of AOD-assisted laser stimulation and optogenetic tools provides a flexible solution for manipulating neuronal activity at high efficiency and with high temporal precision