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The highlighted energy consumption of Internet data center (IDC) in China has become a pressing issue with the implementation of the Chinese dual carbon strategic goal. This paper provides a comprehensive review of cooling technologies for IDC, including air cooling, free cooling, liquid cooling, thermal energy storage cooling and building envelope. Firstly, the environmental requirements for the computer room and the main energy consumption items for IDC are analyzed. The evaluation indicators and government policies for promoting green IDC are also summarized. Next, the traditional cooling technology is compared to four new cooling technologies to find effective methods to maximize energy efficiency in IDC. The results show that traditional cooling consumes a significant amount of energy and has low energy efficiency. The application of free cooling can greatly improve the energy efficiency of IDC, but its actual implementation is highly dependent on geographical and climatic conditions. Liquid cooling, on the other hand, has higher energy efficiency and lower PUE compared to other cooling technologies, especially for high heat density servers. However, it is not yet mature and its engineering application is not widespread. In addition, thermal energy storage (TES) based cooling offers higher energy efficiency but must be coupled with other cooling technologies. Energy savings can also be achieved through building envelope improvements. Considering the investment and recovery period for IDC, it is essential to seek efficient cooling solutions that are suitable for IDC and take into account factors such as IDC scale, climate conditions, maintenance requirements, etc. This paper serves as a reference for the construction and development of green IDC in China.

Optineurin is an important autophagy receptor involved in several selective autophagy processes, during which its function is regulated by TBK1. Mutations of optineurin and TBK1 are both associated with neurodegenerative diseases. However, the mechanistic basis underlying the specific interaction between optineurin and TBK1 is still elusive. Here we determine the crystal structures of optineurin/TBK1 complex and the related NAP1/TBK1 complex, uncovering the detailed molecular mechanism governing the optineurin and TBK1 interaction, and revealing a general binding mode between TBK1 and its associated adaptor proteins. In addition, we demonstrate that the glaucoma-associated optineurin E50K mutation not only enhances the interaction between optineurin and TBK1 but also alters the oligomeric state of optineurin, and the ALS-related TBK1 E696K mutation specifically disrupts the optineurin/TBK1 complex formation but has little effect on the NAP1/TBK1 complex. Thus, our study provides mechanistic insights into those currently known disease-causing optineurin and TBK1 mutations found in patients. Mutations in optineurin that cause defects in the interaction with TBK1 are associated with neurodegenerative diseases. Here, the authors report the structure of this complex, and outline a general binding mode for these proteins.

The rapid development of the drone industry has facilitated the emergence of concepts such as urban air mobility (UAM), driving a wave of air logistics in urban very low-level (VLL) airspace. However, existing trajectory planning algorithms do not adequately consider the ground risks and secondary conflicts arising from high-density operations in urban VLL airspace. To address these challenges, this paper proposes a two-stage hierarchical 4D trajectory planning method to minimize multiple risks. Specifically, the method consists of a risk-aware global planning module (RAGPM) for preflight trajectory planning and a non-secondary conflict local planning module (NCLPM) for in-flight conflict avoidance. Consequently, low-risk trajectory without secondary conflict can be found in complex environments with high-density operations, as illustrated by extensive experiments.

Periodontitis is the leading cause of tooth loss, with alveolar bone resorption serving as its fundamental pathological feature. Identifying key regulatory genes and molecular mechanisms is essential for enhancing preventive and therapeutic strategies. Nevertheless, reliable biomarkers and comprehensive regulatory networks have yet to be elucidated. This study aims to systematically identify candidate alveolar bone resorption hub genes (ABRHUB) and their regulatory networks through bioinformatics analysis. Our objective is to establish a bioinformatics foundation for generating hypotheses about the mechanisms underlying periodontitis progression and to identify potential targets for future experimental validation. The GSE16134 dataset extracted from the GEO database was utilized to screen differentially expressed genes in patients with periodontitis and explore the significance of alveolar bone resorption in the prevention and treatment of this condition. Furthermore, these genes were intersected with modular genes screened by weighted gene co-expression network analysis (WGCNA) as well as osteoclast-related genes obtained from molecular characterization databases, and co-expression differential genes (co-DEGs) were obtained. The co-DEGs were subjected to in-depth analysis using various machine learning algorithms. The validation set GSE10334 and qRT-PCR analysis were utilized for double validation, ultimately confirming ABRHUB. The diagnostic value and immune relevance of ABRHUB were further evaluated, and the potential miRNAs and lncRNAs associated with these key genes were predicted using relevant databases. A significant correlation exists between alveolar bone resorption and periodontitis. Through differential analysis of multiple databases and the integration of machine learning techniques, we identified four key ABRHUB genes: NEDD9, P2RX5, CSF1R and NPR3. Subsequently, we validated these genes using the GSE10334 validation set and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses, and constructed diagnostic and risk models to elucidate the potential utility of ABRHUB in predicting alveolar bone resorption. Furthermore, the calibration curves we established further validated the accuracy of the model predictions. Ultimately, based on these ABRHUB genes, we constructed a lncRNA-miRNA-mRNA molecular regulatory network, providing a significant bioinformatics foundation for future studies. Four genes associated with osteoclast function, namely NEDD9, P2RX5, CSF1R and NPR3, may serve as potential candidate biomarkers for alveolar bone resorption. Notably, the down-regulation of miR-1260b, miR-1224-5p, miR-3156-5p and miR-4286 may contribute to the progression of periodontitis by promoting the expression of NEDD9, P2RX5 and CSF1R.

Myosin VI plays crucial roles in diverse cellular processes. In autophagy, Myosin VI can facilitate the maturation of autophagosomes through interactions with Tom1 and the autophagy receptors, Optineurin, NDP52 and TAX1BP1. Here, we report the high-resolution crystal structure of the C-terminal cargo-binding domain (CBD) of Myosin VI in complex with Tom1, which elucidates the mechanistic basis underpinning the specific interaction between Myosin VI and Tom1, and uncovers that the C-terminal CBD of Myosin VI adopts a unique cargo recognition mode to interact with Tom1 for tethering. Furthermore, we show that Myosin VI can serve as a bridging adaptor to simultaneously interact with Tom1 and autophagy receptors through two distinct interfaces. In all, our findings provide mechanistic insights into the interactions of Myosin VI with Tom1 and relevant autophagy receptors, and are valuable for further understanding the functions of these proteins in autophagy and the cargo recognition modes of Myosin VI. Myosin VI can facilitate the maturation of autophagosomes in autophagy through interactions with Tom1 and autophagy receptors. Here authors report the structure of the cargobinding domain of Myosin VI in complex with Tom1, which provides insights into Myosin IV’s cargo recognition modes.

Periodontitis is one of the most prevalent inflammatory disease worldwide, which affects 11% of the global population and is a major cause of tooth loss. Recently, oxidative stress (OS) has been found to be the pivital pathophysiological mechanism of periodontitis, and overactivated OS will lead to inflammation, apoptosis, pyroptosis and alveolar bone resorption. Interestingly, heme oxygenase-1 (HO-1), a rate-limiting enzyme in heme degradation, can exert antioxidant activites through its products—carbon monoxide (CO), Fe 2+ , biliverdin and bilirubin in the inflammatory microenvironment, thus exhibiting anti-inflammatory, anti-apoptotic, anti-pyroptosis and bone homeostasis-regulating properties. In this review, particular focus is given to the role of HO-1 in periodontitis, including the spatial-temporal expression in periodental tissues and pathophysiological mechanisms of HO-1 in periodontitis, as well as the current therapeutic applications of HO-1 targeted drugs for periodontitis. This review aims to elucidate the potential applications of various HO-1 targeted drug therapy in the management of periodontitis, investigate the influence of diverse functional groups on HO-1 and periodontitis, and pave the way for the development of a new generation of therapeutics that will benefit patients suffering from periodontitis.

Interferon regulatory factor 7 (IRF7)-mediated type I interferon antiviral response is crucial for regulating the host following viral infection in chickens. Infectious bursal disease virus (IBDV) is a double-stranded RNA virus that induces immune suppression and high mortality rates in chickens aged 3-6 weeks. Previous studies have shown that IBDV infection antagonizes the type I interferon production to facilitate viral replication in the cell, and IRF7 signaling might play an important role. However, the underlying mechanisms that enable IBDV to block the IRF7 pathway remain unclear. In this study, we found that IRF7 and IFN-β expression were suppressed in DF-1 cells during infection with very virulent IBDV (vvIBDV), but not with attenuated IBDV, while the virus continued to replicate. Overexpression of IRF7 inhibits IBDV replication while knocking down IRF7 promotes IBDV replication. Overexpression of IRF7 couldn’t compensate the IRF7 protein level in vvIBDV-infected cells, which suggested that IRF7 protein was degraded by IBDV infection. By using inhibitors, the degradation of IRF7 was found to be related to the proteasome pathway. Further study revealed that IRF7 was observed to interact and colocalize with the IBDV VP3 protein. Consistent with IBDV infection results, IBDV VP3 protein was observed to inhibit the IRF7-IFN-β expression, affect the degradation of IRF7 protein via proteasome pathway. All these results suggest that the IBDV exploits IRF7 by affecting its expression and proteasome degradation via the viral VP3 protein to facilitate viral replication in the cells. These findings revealed a novel mechanism that IBDV uses to evade host antiviral defense.

RIPK1, a death domain-containing kinase, has been recognized as an important therapeutic target for inhibiting apoptosis, necroptosis, and inflammation under pathological conditions. RIPK1 kinase inhibitors have been advanced into clinical studies for the treatment of various human diseases. One of the current bottlenecks in developing RIPK1 inhibitors is to discover new approaches to inhibit this kinase as only limited chemotypes have been developed. Here we describe Necrostatin-34 (Nec-34), a small molecule that inhibits RIPK1 kinase with a mechanism distinct from known RIPK1 inhibitors such as Nec-1s. Mechanistic studies suggest that Nec-34 stabilizes RIPK1 kinase in an inactive conformation by occupying a distinct binding pocket in the kinase domain. Furthermore, we show that Nec-34 series of compounds can synergize with Nec-1s to inhibit RIPK1 in vitro and in vivo. Thus, Nec-34 defines a new strategy to target RIPK1 kinase and provides a potential option of combinatorial therapy for RIPK1-mediated diseases.

NDP52 and TAX1BP1, two SKIP carboxyl homology (SKICH) domain-containing autophagy receptors, play crucial roles in selective autophagy. The autophagic functions of NDP52 and TAX1BP1 are regulated by TANK-binding kinase 1 (TBK1), which may associate with them through the adaptor NAP1. However, the molecular mechanism governing the interactions of NAP1 with NDP52 and TAX1BP1, as well as the effects induced by TBK1-mediated phosphorylation of NDP52 and TAX1BP1, remains elusive. Here, we report the atomic structures of the SKICH regions of NDP52 and TAX1BP1 in complex with NAP1, which not only uncover the mechanistic bases underpinning the specific interactions of NAP1with the SKICH domains of NDP52 and TAX1BP1 but also reveal the binding mode of a SKICH domain. Moreover, we uncovered that the SKICH domains of NDP52 and TAX1BP1 share a general binding mode to interact with NAP1. Finally, we also evaluated the currently known TBK1-mediated phosphorylation sites in the SKICH domains of NDP52 and TAX1BP1 on the basis of their interactions with NAP1. In all, our findings provide mechanistic insights into the interactions of NAP1 with NDP52 and TAX1BP1, and are valuable for further understanding the functions of these proteins in selective autophagy.