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Multinucleated cells are present in lung tissues of patients infected by SARS-CoV-2. Although the spike protein can cause the fusion of infected cells and ACE2-expressing cells to form syncytia and induce damage, how host cell responses to this damage and the role of DNA damage response (DDR) signals in cell fusion are still unclear. Therefore, we investigated the effect of SARS-CoV-2 spike protein on the fusion of homologous and heterologous cells expressing ACE2 in vitro models, focusing on the protein levels of ATR and ATM, the major kinases responding to DNA damage, and their substrates CHK1 and CHK2. We found that both homologous and heterologous cell fusion activated the ATR-CHK1 and ATM-CHK2 signaling axis and induced the aggregation of γH2AX, 53BP1 and RAD51 in syncytia. In addition, siRNA or inhibitors of ATM and ATR suppressed syncytia formation by decreasing the level of S protein. These results showed the important role of DDR in stabilizing the S protein and in favoring its induction of cell fusion and syncytium formation, suggesting that the virus exploits the host DDR to facilitate its spread among infected cells., (© 2024 Wiley Periodicals LLC.)

Acrylamide (ACR), a chemical extensively utilized in industry and food processing sectors, has been recognized for its potentially irreversible adverse effect on male reproductive system; however, the underlying mechanism remains elusive. Our study reveals that ACR markedly triggers oxidative stress-mediated autophagy and upregulates the expression of GABAA-receptor-associated protein like-1 (GABARAPL1). Intriguingly, overexpression of GABARAPL1 significantly induces autophagy, while its knockdown alleviates ACR-induced autophagic responses, underscoring its pivotal function. Furthermore, we demonstrate that transcription factors cAMP response element-binding protein 1 (CREB1) and POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) synergistically enhance Gabarapl1 gene transcription by interacting with its promoter region, contributing to ACR-induced autophagy in mouse Leydig cells. Notably, our findings suggest a reciprocal regulation between PATZ1 and CREB1. This study suggests the critical role of GABARAPL1 in ACR-induced autophagy of mouse Leydig cells, shedding light on the underlying mechanism of ACR-caused male reproductive impairment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Formononetin (FMN), an isoflavone mainly derived from leguminous plants, is a natural secondary metabolite with valuable pharmacological effects in the regulation of numerous chronic diseases. This study aimed to investigate the influence of FMN on liver fibrosis and clarify the underlying mechanisms. In vivo FMN administration protected mice from BDL or CCl 4 -induced liver fibrosis. In vitro experimental findings revealed the FMN-mediated inhibitory effects on hepatic stellate cell (HSC) activation. Transcriptome analyses showed that YAP silencing and the subsequent HSC senescence might be responsible for the FMN-mediated antifibrotic outcomes. Furthermore, FMN suppressed EZH2 and its substrate H3K27me3, which are essential for YAP activation and HSC senescence. Remarkably, EZH2 overexpression reversed the FMN potential therapeutic effects on YAP that impact HSC senescence. Our study demonstrated that FMN potentially mitigated hepatic fibrosis by inhibiting EZH2/YAP axis and promoting HSC senescence. Together, these findings provide insights into the prospective therapeutic targets of FMN in liver fibrosis management.

Molecular motor amphiphiles have already been widely attempted for dynamic nanosystems across multiple length-scale for developments of small functional materials, including controlling macroscopic foam properties, amplifying motion as artificial molecular muscles, and serving as extracellular matrix mimicking cell scaffolds. However, limiting examples of bola-type molecular motor amphiphiles are considered for constructing macroscopic biomaterials. Herein, this work presents the designed two second generation molecular motor amphiphiles, motor bola-amphiphiles (MBAs). Aside from the photoinduced motor rotation of MBAs achieved in both organic and aqueous media, the rate of recovering thermal helix inversion step can be controlled by the rotor part with different steric hindrances. Dynamic assembled structures of MBAs are observed under (cryo)-transmission electron microscopy (TEM). This dynamicity assists MBAs in further assembling as macroscopic soft scaffolds by applying a shear-flow method. Upon photoirradiation, the phototropic bending function of MBA scaffolds is observed, demonstrating the amplification of molecular motion into macroscopic phototropic bending functions at the macroscopic length-scale. Since MBAs are confirmed with low cytotoxicity, human bone marrow-derived mesenchymal stem cells (hBM-MSCs) can grow on the surface of MBA scaffolds. These results clearly demonstrate the concept of designing MBAs for developing photoresponsive dynamic functional materials to create new-generation soft robotic systems and cell-material interfaces., (© 2024 Wiley‐VCH GmbH.)

As one of the endocrine-disrupting chemicals (EDCs), dibutyl phthalate (DBP) has been extensively used in industry. DBP has been shown to cause damage to Leydig cells, yet its underlying mechanism remains elusive. In this study, we show that DBP induces ferroptosis of mouse Leydig cells via upregulating the expression of Sp2, a transcription factor. Also, Sp2 is identified to promote the transcription of Vdac2 gene by binding to its promoter and subsequently involved in DBP-induced ferroptosis of Leydig cells. In addition, DBP is proved to induce ferroptosis via inducing oxidative stress, while inhibition of oxidative stress by melatonin alleviates DBP-induced ferroptosis and upregulation of Sp2 and VDAC2. Taken together, our findings demonstrate that melatonin can alleviate DBP-induced ferroptosis of mouse Leydig cells via inhibiting oxidative stress-triggered Sp2/VDAC2 signals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

An AI-empowered indoor digital contact-tracing system was developed using a centralized architecture and advanced low-energy Bluetooth technologies for indoor positioning, with careful preservation of privacy and data security. We analyzed the contact pattern data from two RCHs and investigated a COVID-19 outbreak in one study site. To evaluate the effectiveness of the system in containing outbreaks with minimal contacts under quarantine, a simulation study was conducted to compare the impact of different quarantine strategies on outbreak containment within RCHs. The significant difference in contact hours between weekdays and weekends was observed for some pairs of RCH residents and staff during the two-week data collection period. No significant difference between secondary cases and uninfected contacts was observed in a COVID-19 outbreak in terms of their demographics and contact patterns. Simulation results based on the collected contact data indicated that a threshold of accumulative contact hours one or two days prior to diagnosis of the index case could dramatically increase the efficiency of outbreak containment within RCHs by targeted isolation of the close contacts. This study demonstrated the feasibility and efficiency of employing an AI-empowered system in indoor digital contact tracing of outbreaks in RCHs in the post-pandemic era., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Natural products have provided abundant sources of lead compounds for new drug discovery and development over the past centuries. Curcumin is a lipophilic polyphenol isolated from turmeric, a plant used in traditional Asian medicine for centuries. Despite the low oral bioavailability, curcumin exhibits profound medicinal value in various diseases, especially liver and gut diseases, bringing an interest in the paradox of its low bioavailability but high bioactivity. Several latest studies suggest that curcumin's health benefits may rely on its positive gastrointestinal effects rather than its poor bioavailability solely. Microbial antigens, metabolites, and bile acids regulate metabolism and immune responses in the intestine and liver, suggesting the possibility that the liver-gut axis bidirectional crosstalk controls gastrointestinal health and diseases. Accordingly, these pieces of evidence have evoked great interest in the curcumin-mediated crosstalk among liver-gut system diseases. The present study discussed the beneficial effects of curcumin against common liver and gut diseases and explored the underlying molecular targets, as well as collected evidence from human clinical studies. Moreover, this study summarized the roles of curcumin in complex metabolic interactions in liver and intestine diseases supporting the application of curcumin in the liver-gut system as a potential therapeutic option, which opens an avenue for clinical use in the future.

Hepatic gluconeogenesis is crucial for maintaining blood glucose during starvation, and a major contributor for hyperglycemia. Cellular redox state is related to mitochondrial biology and regulates conversion of specific metabolites to glucose. General control of amino acid synthesis 5 (GCN5) like-1 (GCN5L1) is a mitochondria-enriched protein which modulates glucose and amino acid metabolism. Here we show a new regulatory mode of GCN5L1 on gluconeogenesis using lactate and glycerol. We observed GCN5L1 deletion dramatically inhibited glucose production derived from glycerol and lactate, due to increased cytosolic redox state. The underlying mechanism is that GCN5L1 directly binds to the key component of mitochondrial shuttle glycerol phosphate dehydrogenase 2 (GPD2) and modulates its activity. These results have significant implications for understanding the physiological role and regulatory mechanism of mitochondrial shuttle in diabetes development and provide a novel therapeutic potential for diabetes., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Glutaminolysis is a critical metabolic process that promotes cancer cell proliferation, including hepatocellular carcinoma (HCC). Delineating the molecular control of glutaminolysis could identify novel targets to ameliorate this oncogenic metabolic pathway. Here, we evaluated the role of general control of amino acid synthesis 5 like 1 (GCN5L1), a regulator of mitochondrial protein acetylation, in modulating the acetylation and activity of glutaminase to regulate HCC development., Methods: Cell proliferation was determined by MTT, 2D and soft agar clone formation assays and orthotopic tumour assays in nude mice. GLS1/2 acetylation and activities were measured in cells and tumours to analyse the correlation with GCN5L1 expression and mTORC1 activation., Results: Hepatic GCN5L1 ablation in mice markedly increased diethylnitrosamine (DEN)-induced HCC, and conversely, the transduction of mitochondrial-restricted GCN5L1 protected wild-type mice against HCC progression in response to DEN and carbon tetrachloride (CCl 4 ) exposure. GCN5L1-depleted HepG2 hepatocytes enhanced tumour growth in athymic nude mice. Mechanistically, GCN5L1 depletion promoted cell proliferation through mTORC1 activation. Interestingly, liver-enriched glutaminase 2 (GLS2) appears to play a greater role than ubiquitous and canonical tumour-enriched glutaminase 1 (GLS1) in promoting murine HCC. Concurrently, GCN5L1 promotes acetylation and inactivation of both isoforms and increases enzyme oligomerisation. In human HCC tumours compared to adjacent tissue, there were variable levels of mTORC1 activation, GCN5L1 levels and glutaminase activity. Interestingly, the levels of GCN5L1 inversely correlated with mTORC1 activity and glutaminase activity in these tumours., Conclusions: Our study identified that glutaminase activity, rather than GLS1 or GLS2 expression, is the key factor in HCC development that activates mTORC1 and promotes HCC. In the Kaplan-Meier analysis of liver cancer, we found that HCC patients with high GCN5L1 expression survived longer than those with low GCN5L1 expression. Collectively, GCN5L1 functions as a tumour regulator by modulating glutaminase acetylation and activity in the development of HCC., (© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Nature sets a great example of how to precisely control self-assembly to obtain distinct structures upon external stimuli and perform specific functions to sustain important biological tasks. In the present study, we report the design and control of self-assembly of an amphiphilic conjugated alkene in water. The morphologies of the self-assembled structures are highly dependent on the anions. The hydrophilic tosylate group can trigger the formation of nanotubes, while the less-hydrophilic inorganic bromide generates vesicles. The interchange of the two different structures can be controlled by employing different anions combined with a couple of reactions that act as signals. The result shown here provides an important tool for manipulating self-assembled behaviors in water and paves the way toward more complex systems., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Changes in species composition across communities, i.e., β-diversity, is a central focus of ecology. Compared to macroorganisms, the β-diversity of soil microbes and its drivers are less studied. Whether the determinants of soil microbial β-diversity are consistent between soil depths and between abundant and rare microorganisms remains controversial. Here, using the 16S-rRNA of soil bacteria and archaea sampled at different soil depths (0-10 and 30-50 cm) from 32 sites along an aridity gradient of 1500 km in the temperate grasslands in northern China, we compared the effects of deterministic and stochastic processes on the taxonomic and phylogenetic β-diversity of soil microbes. Using variation partitioning and null models, we found that the taxonomic β-diversity of the overall bacterial communities was more strongly determined by deterministic processes in both soil layers (the explanatory power of environmental distance in topsoil: 25.4%; subsoil: 47.4%), while their phylogenetic counterpart was more strongly determined by stochastic processes (the explanatory power of spatial distance in topsoil: 42.1; subsoil 24.7%). However, in terms of abundance, both the taxonomic and phylogenetic β-diversity of the abundant bacteria in both soil layers was more strongly determined by deterministic processes, while those of rare bacteria were more strongly determined by stochastic processes. In comparison with bacteria, both the taxonomic and phylogenetic β-diversity of the overall abundant and rare archaea were strongly determined by deterministic processes. Among the variables representing deterministic processes, contemporary and historical climate and aboveground vegetation dominated the microbial β-diversity of the overall and abundant microbes of both domains in topsoils, but soil geochemistry dominated in subsoils. This study presents a comprehensive understanding on the β-diversity of soil microbial communities in the temperate grasslands in northern China. Our findings highlight the importance of soil depth, phylogenetic turnover, and species abundance in the assembly processes of soil microbial communities.

Elevational range shifts of mountain species in response to climate change have profound impact on mountain biodiversity. However, current evidence indicates great controversies in the direction and magnitude of elevational range shifts across species and regions. Here, using historical and recent occurrence records of 83 plant species in a subtropical mountain, Mt. Gongga (Sichuan, China), we evaluated changes in species elevation centroids and limits (upper and lower) along elevational gradients, and explored the determinants of elevational changes. We found that 63.9% of the species shifted their elevation centroids upward, while 22.9% shifted downward. The changes in centroid elevations and range size were more strongly correlated with changes in lower than upper limits of species elevational ranges. The magnitude of centroid elevation shifts was larger than predicted by climate warming and precipitation changes. Our results show complex changes in species elevational distributions and range sizes in Mt. Gongga, and that climate change, species traits and climate adaptation of species all influenced their elevational movement. As Mt. Gongga is one of the global biodiversity hotspots, and contains many threatened plant species, these findings provide support to future conservation planning., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Protected areas (PAs) play a pivotal role in maintaining viable populations of species and minimizing their habitat loss. Globally, there are currently over 200,000 PAs that cover approximately 15% of land area. The post-2020 global biodiversity framework aims to expand this coverage to 30% by 2030. However, focusing only on the percentage coverage of PAs without evaluating their effectiveness may fail to achieve conservation goals. Here, we use a multidimensional approach incorporating species, climate and anthropogenic vulnerabilities to assess the threat levels in over 2500 PAs in China. We identify nearly 10% of PAs as the most threatened PAs in China and about one-fifth PAs as hotspots of climate and anthropogenic vulnerabilities. We also find high climate instability in species vulnerability hotspots, suggesting an elevated likelihood of species' extirpation therein. Our framework could be useful in assessing resiliency of global protected lands and also in selecting near optimal areas for their future expansion.

The abuse of antibiotics has led to the emergence of multidrug-resistant bacteria, which is becoming a serious worldwide problem people have to face. In our previous study, temporin-GHa (GHa) cloned from Hylarana guentheri showed antimicrobial activity against Gram-positive bacteria. In order to improve its therapeutic potential, we used a template-based and a database-assisted design to obtain three derived peptides by replacing the histidine at both ends of GHa with lysine, which exhibited faster and stronger bactericidal activity and a broader spectrum than the parent peptide. GHaK and GHa4K targeted to the bacterial membrane to exert their antibacterial activities at a faster membrane damage rate. The derived peptides inhibited the initial adhesion and the formation of Staphylococcus aureus biofilms, and eradicated the mature biofilms, which indicated that the derived peptides effectively penetrated the biofilm and killed bacteria. The therapeutic index (TI) and cell selectivity index (CSI) of the derived peptides increased significantly, which means a broader therapeutic window of the derived peptides. The derived peptides with improved activity and cell selectivity have the potential to be the promising candidates for the treatment of S. aureus infections. Our research also provides new insights into the design and development of antimicrobial peptides.

Sour rot, caused by Geotrichum citriaurantii (G. citri-aurantii.), is one of the most serious grapevine secondary infection diseases in China. We have determined that pterostilbene, the most important phytoalexin, effectively inhibits the activity of G. citri-aurantii. To study the synthesis mechanism of pterostilbene against G. citri-aurantii in grape, we initially detected the content of pterostilbene present in grapes infected by G. citri-aurantii with the use of UHPLC-QQQ-MS 2 . Pterostilbene levels are controlled by the resveratrol O-methyltransferase (ROMT) gene, and within grape samples is positively related to the accumulation of resveratrol. The pPIC9k-ROMT vector and plasmid pCAMBIA2300-GFP-ROMT were constructed for expression purposes. The pPIC9k-ROMT vector was expressed in Pichia pastoris GS115 and plasmid pCAMBIA2300-GFP-ROMT was expressed in onion. Analysis of qRT-PCR amplification samples revealed that gene expression was induced rapidly in grape as a defense against G. citri-aurantii. Western blot analysis verified that the recombinant protein was successfully expressed. PRACTICAL APPLICATIONS: Pterostilbene is a trace and efficient phytoalexins produced by plant' secondary metabolism, which exhibits good pharmacological activity. As an important protective agent in plants, it can improve the antioxidant capacity and resistance to adversity of plants. However, the method which could be used for mass production of pterostilbene has not been reported currently. The key gene of pterostilbene biosynthesis was investigated and verified in this paper, which provides the theoretical basis for the industrial production of pterostilbene. The study of pterostilbene is significant for the prevention and treatment of G. citri-aurantii disease, and has important practical applications for the development and production of pesticides., (© 2019 Wiley Periodicals, Inc.)

In order to enhance the reliability and anti-interference performance of wireless sensor network (WSN) data transmission, this paper designs the low power scheme of the WSN from the angle of error correction coding and proposes the hybrid check matrix construction (HC) algorithm based on iterative coding algorithms with linear coding complexity. The algorithm first improves the traditional iterative coding algorithm, making it suitable for non-binary low-density parity check (LDPC) codes. Then, the algorithm applies the backward iteration method to change the coding scheme and uses the check matrix construction method so that the progressive edge growth (PEG) algorithm has a lower triangular structure, which is used as a base matrix. An improved quasi-cyclic LDPC (QC-LDPC) algorithm, with a lower triangular structure, is used to generate a cyclic shift matrix and a finite domain coefficient matrix. Simultaneously, the short loop is eliminated and the optimal check matrix is selected for use in the channel coding process. The non-binary LDPC-CPM system is modeled and simulated. The simulation results show that the non-binary LDPC code constructed by the HC algorithm not only has linear coding and storage complexity but also has strong error correction capability. The design of non-binary LDPC-CPM system parameters can enhance the reliability, anti-jamming capability and reduce the complexity and reduce the complexity of the WSN.

In order to improve the performance of non-binary low-density parity check codes (LDPC) hard decision decoding algorithm and to reduce the complexity of decoding, a sum of the magnitude for hard decision decoding algorithm based on loop update detection is proposed. This will also ensure the reliability, stability and high transmission rate of 5G mobile communication. The algorithm is based on the hard decision decoding algorithm (HDA) and uses the soft information from the channel to calculate the reliability, while the sum of the variable nodes' (VN) magnitude is excluded for computing the reliability of the parity checks. At the same time, the reliability information of the variable node is considered and the loop update detection algorithm is introduced. The bit corresponding to the error code word is flipped multiple times, before this is searched in the order of most likely error probability to finally find the correct code word. Simulation results show that the performance of one of the improved schemes is better than the weighted symbol flipping (WSF) algorithm under different hexadecimal numbers by about 2.2 dB and 2.35 dB at the bit error rate (BER) of 10 -5 over an additive white Gaussian noise (AWGN) channel, respectively. Furthermore, the average number of decoding iterations is significantly reduced., Competing Interests: The authors declare no conflict of interest.