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BACKGROUNDWeakly virulent environmental mycobacteria (EM) can cause severe disease in HLA-DRB1*15:02 or 16:02 adults harboring neutralizing anti-IFN-γ autoantibodies (nAIGAs). The overall prevalence of nAIGAs in the general population is unknown, as are the penetrance of nAIGAs in HLA-DRB1*15:02 or 16:02 individuals and the proportion of patients with unexplained, adult-onset EM infections carrying nAIGAs.METHODSThis study analyzed the detection and neutralization of anti-IFN-γ autoantibodies (auto-Abs) from 8,430 healthy individuals of the general population, 257 HLA-DRB1*15:02 or 16:02 carriers, 1,063 patients with autoimmune disease, and 497 patients with unexplained severe disease due to EM.RESULTSWe found that anti-IFN-γ auto-Abs detected in 4,148 of 8,430 healthy individuals (49.2%) from the general population of an unknown HLA-DRB1 genotype were not neutralizing. Moreover, we did not find nAIGAs in 257 individuals carrying HLA-DRB1* 15:02 or 16:02. Additionally, nAIGAs were absent in 1,063 patients with an autoimmune disease. Finally, 7 of 497 patients (1.4%) with unexplained severe disease due to EM harbored nAIGAs.CONCLUSIONThese findings suggest that nAIGAs are isolated and that their penetrance in HLA-DRB1*15:02 or 16:02 individuals is low, implying that they may be triggered by rare germline or somatic variants. In contrast, the risk of mycobacterial disease in patients with nAIGAs is high, confirming that these nAIGAs are the cause of EM disease.FUNDINGThe Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI095983 and U19AIN1625568), the National Center for Advancing Translational Sciences (NCATS), the NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), the French National Research Agency (ANR) under the Investments for the Future program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), ANR-GENMSMD (ANR-16-CE17-0005-01), ANR-MAFMACRO (ANR-22-CE92-0008), ANRSECTZ170784, the French Foundation for Medical Research (FRM) (EQU201903007798), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AI2D (ANR-22-CE15-0046) projects, the ANR-RHU program (ANR-21-RHUS-08-COVIFERON), the European Unions Horizon 2020 research and innovation program under grant agreement no. 824110 (EASI-genomics), the Square Foundation, Grandir - Fonds de solidarité pour lenfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the Battersea & Bowery Advisory Group, William E. Ford, General Atlantics Chairman and Chief Executive Officer, Gabriel Caillaux, General Atlantics Co-President, Managing Director, and Head of business in EMEA, and the General Atlantic Foundation, Institut National de la Santé et de la Recherche Médicale (INSERM) and of Paris Cité University. JR was supported by the INSERM PhD program for doctors of pharmacy (poste daccueil INSERM). JR and TLV were supported by the Bettencourt-Schueller Foundation and the MD-PhD program of the Imagine Institute. MO was supported by the David Rockefeller Graduate Program, the Funai Foundation for Information Technology (FFIT), the Honjo International Scholarship Foundation (HISF), and the New York Hideyo Noguchi Memorial Society (HNMS).

Abstract This paper proposes an adaptive saturation module to enhance the transient stability of grid‐following inverters after voltage‐dip inception and fault‐clearance moment. The equal‐area criterion reveals that a large acceleration area will be obtained due to the step change of current reference according to grid codes, which may lead to the loss of synchronism with the grid. It is found that the saturation module used with the phase‐locked loop can enhance the transient stability performance by reducing the acceleration area. To simultaneously adapt to the two cases (the inception and clearance of the voltage‐dip fault), an adaptive saturation module that can automatically adjust the clamping mode is proposed, which is the main contribution of the paper. The selection of the threshold value for the saturation module is also presented. A comprehensive comparison is made between the proposed solution and state‐of‐art solutions. Finally, the effectiveness of the proposed control strategy is confirmed by the experimental tests.

Opacification of intraocular lens(IOL)is a rare postoperative complication of cataract surgery. Its occurrence may be associated with various factors, including manufacturing processes, IOL material, patient factors, and surgical intervention. IOL opacification has been reported in all kinds of materials, and the morphological changes and pathological features of IOL opacification from different materials have their own characteristics, with varying clinical manifestations. With the development of related researches, the understanding of IOL opacification is becoming more and more comprehensive. This article reviews the latest research progress in the morphology, etiology, diagnosis and treatment of IOL opacification, with a view to providing guidance for current clinical work and potential directions for future scientific research.

Abstract Background Osteoarthritis (OA) is the most prevalent type of arthritis and the main reason for progressive disability in middle-aged and older people. Studies of candidate genes may provide a novel insight and treatment strategy for knee osteoarthritis (KOA). The aim of this study was to investigate the relationship between KOA susceptibility and single-nucleotide polymorphism (SNP) of the ADAMTS-5 gene. Materials and methods The case group included 188 patients from Luoyang Orthopedic Hospital with clinically and radiographically diagnosed primary KOA, and the control group included 100 age-matched individuals without KOA. Fifteen ADAMTS-5 SNPs were assayed using MALDI-TOF MS. Allelic and haplotypic frequencies were compared between the groups. The relationship between genotype distribution and risk of KOA was analyzed by multivariate logistic regression. Results The frequency of A allele in rs2249350 site in the KOA group was significantly lower (odds ratio [OR]: 0.761; 95% confidence interval [95% CI]: 0.612–0.947; P = 0.016), while that of C allele was higher than that in the control group (OR: 1.176; 95% CI: 1.025–1.351; P = 0.016). AA genotype and gene model, especially recessive gene model at rs2249350 locus, negatively correlated with KOA risk after adjustment for sex, body mass index, age, and occupation (AA vs. CC: OR: 0.288; 95% CI: 0.124–0.669; P = 0.004; AA vs. CA + CC: OR: 0.348; 95% CI: 0.162–0.749; P = 0.007). Meanwhile, one protective haplotype, GA (rs229054, rs2249350) (OR: 0.763; 95% CI: 0.614–0.949; P = 0.017), and one high-risk haplotype, GC (rs229054, rs2249350) (OR: 1.259; 95% CI: 1.032–1.537; P = 0.019), were found in this study. Conclusion Despite a limited sample size, our study suggests that the rs2249350 polymorphism in the ADAMTS-5 gene is one of the genetic factors influencing the risk of KOA. The A allele and AA genotype of rs2249350 may protect from KOA, whereas C allele and CC genotype increase the risk of KOA. In addition, the GA haplotype (rs229054, rs2249350) might be associated with a decreased risk of KOA, whereas the GC haplotype (rs229054, rs2249350) may be a risk factor for KOA. Additional larger-sized studies in more ethnically diverse populations are needed to confirm these findings.

Abstract A universal coordinate system that can ensemble the huge number of cells and capture their heterogeneities is of vital importance for constructing large-scale cell atlases as references for molecular and cellular studies. Studies have shown that cells exhibit multifaceted heterogeneities in their transcriptomic features at multiple resolutions. This nature of complexity makes it hard to design a fixed coordinate system through a combination of known features. It is desirable to build a learnable universal coordinate model that can capture major heterogeneities and serve as a controlled generative model for data augmentation. We developed UniCoord, a specially-tuned joint-VAE model to represent single-cell transcriptomic data in a lower-dimensional latent space with high interpretability. Each latent dimension can represent either discrete or continuous feature, and either supervised by prior knowledge or unsupervised. The latent dimensions can be easily reconfigured to generate pseudo transcriptomic profiles with desired properties. UniCoord can also be used as a pre-trained model to analyze new data with unseen cell types and thus can serve as a feasible framework for cell annotation and comparison. UniCoord provides a prototype for a learnable universal coordinate framework to enable better analysis and generation of cells with highly orchestrated functions and heterogeneities.

Jatropha curcas L. (J. curcas), a shrub plant of the Euphorbiaceae family, has received enormous attention as a promising biofuel plant for the production of biodiesel and medical potential in ethnopharmacology. However, the tumor-promoter toxin phorbol esters present in J. curcas raise concerns for health and environmental risk as its large-scale cultivation limits the use of meal obtained after oil extraction for animal feed. Here, we determined the variation of phorbol ester profiles and contents in eight J. curcas tissues by high-performance liquid chromatography (HPLC) and found phorbol esters present in all parts of the plant except the seed shell. We showed tissue-specific patterns of accumulation of phorbol esters and associated terpenoids at the transcriptional level with high transcript levels in reproductive and young tissues. Genes involved in the same module of terpenoids biosynthesis were positively correlated. We further present diverse abiotic and biotic stresses that had different effects on the accumulation of transcripts in terpenoids shared and branched terpenoid pathways in plant seedlings. The fine-tuning of terpenoids biosynthesis may link with ecological functions in plants under extreme environments and defense against pathogens.

Fermented foods made through microbial growth and enzymatic conversions have been integral to human diets for at least 10,000 years. Recent interest in fermented foods has surged due to their functional properties and health benefits. Cruciferous vegetables of the genus Brassica, such as cabbage, broccoli, and cauliflower, are commonly used to produce fermented foods like sauerkraut, kimchi, pao cai, fermented turnips, and others. These foods are rich in lactic acid bacteria (LAB) and bioactive compounds, which contribute to their potential health-promoting properties. We examined 12 clinical trials investigating fermented foods of the genus Brassica. These studies, which mainly assessed the health benefits of kimchi or sauerkraut consumption, found that regular intake can alleviate symptoms of irritable bowel syndrome (IBS), aid weight loss, and enhance metabolic health. Seven observational studies also observed health benefits when consuming fermented foods of the genus Brassica. Six of the seven observational studies on kimchi intake linked kimchi intake to reduced obesity risk and other health benefits. An observational study linked sauerkraut and cabbage consumption to reduced breast cancer risk. Despite these findings, the exact roles of various microorganisms and bioactive compounds within these health effects require further investigation. This review underscores the potential of fermented cruciferous vegetables as functional foods, and advocates for more clinical trials and mechanistic studies to understand and optimize their health benefits.

Abstract Cellulose fiber-based textiles are ubiquitous in daily life for their processability, biodegradability, and outstanding flexibility. Integrating cellulose textiles with functional coating materials can unlock their potential functionalities to engage diverse applications. Metal-organic frameworks (MOFs) are ideal candidate materials for such integration, thanks to their unique merits, such as large specific surface area, tunable pore size, and species diversity. However, achieving scalable fabrication of MOFs-textiles with high mechanical durability remains challenging. Here, we report a facile and scalable strategy for direct MOF growth on cotton fibers grafted via the diazonium chemistry. The as-prepared ZIF-67-Cotton textile (ZIF-67-CT) exhibits excellent ultraviolet (UV) resistance and organic contamination degradation via the peroxymonosulfate activation. The ZIF-67-CT is also used to encapsulate essential oils such as carvacrol to enable antibacterial activity against E. coli and S. aureus. Additionally, by directly tethering a hydrophobic molecular layer onto the MOF-coated surface, superhydrophobic ZIF-67-CT is achieved with excellent self-cleaning, antifouling, and oil-water separation performances. More importantly, the reported strategy is generic and applicable to other MOFs and cellulose fiber-based materials, and various large-scale multi-functional MOFs-textiles can be successfully manufactured, resulting in vast applications in wastewater purification, fragrance industry, and outdoor gears.

Abstract Background Lung cancer, with high morbidity and mortality, is the commonest respiratory system neoplasm, which seriously endangers the life safety of patients. In this study, the effect of PRPS2 on cell progression was preliminarily investigated. Methods Immunohistochemical staining, western blot and reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) were performed to verify the expression level of PRPS2 in lung cancer. Lung cancer cell lines with stable downregulation of PRPS2 were constructed in A549 cells and NCIH460 cells. The function of PRPS2 silencing on the proliferation ability was verified by the EdU and cell colony formation experiment. Scratch and transwell tests were conducted to verify the role of PRPS2 silencing on the migratory and invasive ability of cells. The impact of PRPS2 silencing on cell apoptosis and cell cycle was verified by flow cytometry test. The effects of PRPS2 silencing on apoptosis‐associated proteins were assessed by western blot assay. The function of PRPS2 silencing on tumor growth in vivo was studied through xenograft tumor experiment. Results In comparison with normal tissues, PRPS2 was upregulated in lung cancer tissues. PRPS2 knockdown notably hindered the migratory ability, invasive ability and proliferation, but accelerated cell apoptosis. In vivo experiments confirmed that PRPS2 silencing blocked the growth of transplanted tumors. Conclusion In lung cancer, PRPS2 silencing suppressed the malignant progression, indicating that PRPS2 might be a novel biomarker for lung cancer treatment and diagnosis.

Background and purpose: DDX is an adenosine triphosphate (ATP)-dependent RNA helicase closely related to mRNA regulation, tumor proliferation and invasion. This article aimed to explore the effect of DDX6, a member of the DDX family, on the stability of CKMT1A mRNA, as well as the effect of the DDX6 CKMT1A axis on the proliferation and migration ability of human nasopharyngeal carcinoma cell CNE2 and its molecular mechanism. Methods: We retrieved the data of expressions of DDX6 and CKMT1A in human head and neck squamous cell carcinoma from The Cancer Genome Atlas (TCGA) database and performed a correlation analysis. Western blot was performed to detect the expressions of CKMT1A and DDX6 in human nasopharyngeal carcinoma tissues and normal nasopharyngeal tissues preserved by Affiliated Hospital of Nantong University. This study was approved by the Ethics Committee of Affiliated Hospital of Nantong University (Number: 2022-L114). We used transwell assay to detect cell migration ability, EdU assay to detect cell proliferation ability, and colony formation assay to detect clone formation ability. We transfect with lentivirus and plasmids to construct sh-DDX6, sh-CKMT1A, sh-CKMT1A+sh-DDX6 and oe-CKMT1A cell models derived from the human nasopharyngeal carcinoma cell line CNE2, preserved by Affiliated Hospital of Nantong University, to clarify the impact of DDX6 and CKMT1A expression levels on the malignant biological phenotypes of nasopharyngeal carcinoma cells. BALB/c nude mice subcutaneous xenograft tumor model was constructed to detect the effects of DDX6 and CKMT1A on nasopharyngeal carcinoma cells in mice. RNA stability assay was used to detect the effect of DDX6 knockout on CKMT1A mRNA and further clarify the molecular mechanism of DDX6. Results: DDX6 was highly expressed, CKMT1A level was low in human nasopharyngeal carcinoma tissue, and DDX6 was negatively correlated with CKMT1A expression. DDX6 inhibited protein translation of CKMT1A by disrupting its mRNA stability. Low expression of CKMT1A in CNE2 cells enhanced cell migration and proliferation ability, while high expression inhibited migration and proliferation ability. Knocking out DDX6 reversed the progression of malignant behavior caused by downregulation of CKMT1A. Low expression of CKMT1A promoted tumor cell growth in BALB/cnude mice subcutaneous xenograft tumor model, while low expression of DDX6 inhibited tumor cell growth. Knocking out DDX6 and CKMT1A simultaneously restored the inhibitory effect caused by knocking down DDX6 alone. Conclusion: DDX6 in nasopharyngeal carcinoma cells disrupts the stability of CKMT1A mRNA, negatively regulates CKMT1A protein translation, upregulates the proliferation and migration ability of nasopharyngeal carcinoma cells, and promotes malignant progression of nasopharyngeal carcinoma.

Arteriosclerotic cerebral small vessel disease (aCSVD) is a major cause of stroke and dementia. Although its underlying pathogenesis remains poorly understood, both inflammaging and gut microbiota dysbiosis have been hypothesized to play significant roles. This study investigated the role of gut microbiota in the pathogenesis of aCSVD through a comparative analysis of the gut microbiome and metabolome between CSVD patients and healthy controls. The results showed that patients with aCSVD exhibited a marked reduction in potentially beneficial bacterial species, such as Faecalibacterium prausnitzli and Roseburia intestinalis, alongside an increase in taxa from Bacteroides and Proteobacteria. Integrated metagenomic and metabolomic analyses revealed that alterations in microbial metabolic pathways, including LPS biosynthesis and phenylalanine-tyrosine metabolism, were associated with the status of aCSVD. Our findings indicated that microbial LPS biosynthesis and phenylalanine-tyrosine metabolism potentially influenced the symptoms and progression of aCSVD via pro-inflammatory effect and modulation of systemic neurotransmitters, respectively. These results imply that gut microbiota characteristics may serve as indicators for early detection of aCSVD and as potential gut-directed therapeutic intervention target.

Abstract Flexible electro‐optical dual‐mode sensor fibers with capability of the perceiving and converting mechanical stimuli into digital‐visual signals show good prospects in smart human‐machine interaction interfaces. However, heavy mass, low stretchability, and lack of non‐contact sensing function seriously impede their practical application in wearable electronics. To address these challenges, a stretchable and self‐powered mechanoluminescent triboelectric nanogenerator fiber (MLTENGF) based on lightweight carbon nanotube fiber is successfully constructed. Taking advantage of their mechanoluminescent‐triboelectric synergistic effect, the well‐designed MLTENGF delivers an excellent enhancement electrical signal of 200% and an evident optical signal whether on land or underwater. More encouragingly, the MLTENGF device possesses outstanding stability with almost unchanged sensitivity after stretching for 200%. Furthermore, an extraordinary non‐contact sensing capability with a detection distance of up to 35 cm is achieved for the MLTENGF. As application demonstrations, MLTENGFs can be used for home security monitoring, intelligent zither, traffic vehicle collision avoidance, and underwater communication. Thus, this work accelerates the development of wearable electro‐optical textile electronics for smart human‐machine interaction interfaces.

Abstract The evolution of charge structure involved in lightning discharge of a thunderstorm over the central Tibetan Plateau is investigated for the first time, based on the data from very high frequency interferometer, radar and sounding. During the developing‐mature stage, the TP thunderstorm exhibited a tripolar charge structure evolved from an initial inverted dipole. At the mature stage, a bottom‐heavy tripole charge structure is clearly presented, with a strong lower positive charge center (LPCC) at temperatures above −10°C, a middle negative charge region between −30°C and −15°C, and an upper positive charge region at T

As economically significant species, bivalves maintain intimate contact with external microorganisms during respiration and filter feeding, rendering them prime candidates for investigating microbial communities. Although numerous studies have been conducted on the microbial communities inhabiting the mantles, the composition and functions of the microbial community residing within the coloured mantles remain unclear. The pigments in the coloured areas may attract some microorganisms related to pigments. Thus, in vitro culture can be utilized to rapidly assess the fundamental characteristics of the microbial community present in the coloured mantles. Our results indicated that the microbial community in the coloured mantles of three bivalves (Crassostrea gigas, Mytilus edulis, and Chlamys farreri) responded differently to various media, resulting in pigmentation occurring on tyrosine medium. Further analyses by Metabarcoding revealed a relatively low abundance of melanin-producing strains on the surface of coloured mantles, which may be related to the requirement of melanin-producing strains for a specific nutritional environment. Then, we observed that there were significant differences in the composition of the microbial communities in coloured mantles of the three bivalves, with different bivalves possessing distinct biomarkers. These microorganisms affect the host by regulating the immune system and aiding digestion, nutrient absorption, and nitrification. Correlation analysis showed that multiple metabolites of the three bivalves were strongly correlated with bacterial biomarkers and may play an important role in maintaining the dynamic balance of surface microbial communities. In conclusion, this study discussed the multifaceted effects of microorganisms on the dynamic equilibrium of bivalves microbial communities, exploring the intricate connection between the host and the microbe, as well as the composition of microbial communities. This lays the foundation for comprehending the intricate symbiotic relationship between bivalves and their microbial counterparts and offers a theoretical foundation for the future development of microbial preparations intended for bivalves body surfaces.

An experimental platform to examine the effects of single-phase immersion preheating on lithium-ion battery performance at low temperatures was set up in this study. The performance of lithium-ion batteries at low temperatures can be improved through immersion preheating. After preheating from −15 °C to 15 °C, the battery capacity can recover to over 80 % of its rated capacity. The three influencing factors are inlet flow rate, fluid temperature, and cell spacings. The inlet temperature exerts the most influence on the preheating performance. The warming rate can reach 1.63 °C/min at a temperature of 50 °C. While the increase in flow rate has less influence on the heating rate, it has a greater impact on the temperature difference between cells. The maximum temperature difference between cells can still be kept below 4 °C. The impact of spacing on the heating rate and temperature difference is minimal. The temperature difference can be controlled within 6 °C. Finally, it's important to note that immersion preheating consumes significant amount of energy. The energy consumption of preheating at an ambient temperature of −25 °C exceeds 80 % of the rated capacity of the experimental battery pack.

In this study, we compared the performance of different structures of mini-channel cold plate (MCP) - phase change material (PCM) hybrid thermal management on discharge and thermal runaway. The heat transfer structures for them can be categorized into three types: (a) uncoupled, (b) semi-coupled, and (c) fully coupled. Among these, the semi-coupled design B exhibits the best performance. Specifically, in the high rate discharge condition, the structure can control the battery temperature at 44.37 °C at low coolant mass flow rate, and the temperature at 36.47 °C at high mass flow rate, while the temperature difference (TD) of a single cell does not exceed 2.01 °C. In a low-multiplier discharge zero-energy system, the pack temperature rise can be limited to no more than 10 °C in 35 °C environment. Under external short-circuit conditions, a lower coolant mass flow rate is sufficient to keep the pack temperature at 43.22 °C. Under internal short-circuit thermal runaway (TR), lower coolant mass flow rate can prolong the TR of the adjacent cell up to 521 s, and higher mass flow rate can completely inhibit the occurrence of TR. The objective of this study is to offer valuable references for the design and implementation of hybrid MCP-PCM cooling systems.

Abstract Van der Waals semiconductors exemplified by two-dimensional transition-metal dichalcogenides have promised next-generation atomically thin optoelectronics. Boosting their interaction with light is vital for practical applications, especially in the quantum regime where ultrastrong coupling is highly demanded but not yet realized. Here we report ultrastrong exciton-plasmon coupling at room temperature in tungsten disulfide (WS2) layers loaded with a random multi-singular plasmonic metasurface deposited on a flexible polymer substrate. Different from seeking perfect metals or high-quality resonators, we create a unique type of metasurface with a dense array of singularities that can support nanometre-sized plasmonic hotspots to which several WS2 excitons coherently interact. The associated normalized coupling strength is 0.12 for monolayer WS2 and can be up to 0.164 for quadrilayers, showcasing the ultrastrong exciton-plasmon coupling that is important for practical optoelectronic devices based on low-dimensional semiconductors.

Abstract Background Sufentanil-induced cough is common during the induction of anesthesia. The objective of this study was to determine whether pretreatment with a small dose of esketamine is effective in treating sufentanil-induced cough. Methods 220 patients were screened, and 200 patients who had scheduled elective surgery and were between 18 and 70 years old were randomly divided into two groups. Before sufentanil was administered, esketamine group (group K) was injected with 0.15 mg/kg esketamine at 5 s, and control group (group C) was administered with the same volume. Within 1 min after sufentanil(0.4ug/kg) injection during induction, cough incidence and severity were evaluated. After sufentanil was injected, we recorded its hemodynamic changes and side effects. Results In the esketamine group (group K) and control group (group C), there was an incidence of cough of 5 and 34%, respectively. The esketamine group (group K) had a significantly lower incidence and severity of cough compared to the control group (group C) immediately after sufentanil injection (P 0.05). Conclusion In our study, we found that sufentanil-induced cough was significantly reduced by pretreatment with 0.15 mg/kg esketamine, but with no significant changes in the hemodynamic status. Trial registration Chinese Clinical Trial Registry (ChiCTR2200063821, registered date: 17/09/2022), http://www.chictr.org.cn

Abstract Installing different chemical entities onto crystalline frameworks with well-defined spatial distributions represents a viable approach to achieve ordered and complex synthetic materials. Herein, a covalent organic framework (COF-305) is constructed from tetrakis(4-aminophenyl)methane and 2,3-dimethoxyterephthalaldehyde, which has the largest unit cell and asymmetric unit among known COFs. The ordered complexity of COF-305 is embodied by nine different stereoisomers of its constituents showing specific sequences on topologically equivalent sites, which can be attributed to its building blocks deviating from their intrinsically preferred simple packing geometries in their molecular crystals to adapt to the framework formation. The insight provided by COF-305 supplements the principle of covalent reticular design from the perspective of non-covalent interactions and opens opportunities for pursuing complex chemical sequences in molecular frameworks.

Abstract In this study, we investigated the roles of ROCK1 in regulating structural and functional features of caveolae located at the cell membrane of cardiomyocytes, adipocytes, and mouse embryonic fibroblasts (MEFs) as well as related physiopathological effects. Caveolae are small bulb‐shaped cell membrane invaginations, and their roles have been associated with disease conditions. One of the unique features of caveolae is that they are physically linked to the actin cytoskeleton that is well known to be regulated by RhoA/ROCKs pathway. In cardiomyocytes, we observed that ROCK1 deficiency is coincident with an increased caveolar density, clusters, and caveolar proteins including caveolin‐1 and ‐3. In the mouse cardiomyopathy model with transgenic overexpressing Gαq in myocardium, we demonstrated the reduced caveolar density at cell membrane and reduced caveolar protein contents. Interestingly, coexisting ROCK1 deficiency in cardiomyocytes can rescue these defects and preserve caveolar compartmentalization of β‐adrenergic signaling molecules including β1‐adrenergic receptor and type V/VI adenylyl cyclase. In cardiomyocytes and adipocytes, we detected that ROCK1 deficiency increased insulin signaling with increased insulin receptor activation in caveolae. In MEFs, we identified that ROCK1 deficiency increased caveolar and total levels of caveolin‐1 and cell membrane repair ability after mechanical or chemical disruptions. Together, these results demonstrate that ROCK1 can regulate caveolae plasticity and multiple functions including compartmentalization of signaling molecules and cell membrane repair following membrane disruption by mechanical force and oxidative damage. These findings provide possible molecular insights into the beneficial effects of ROCK1 deletion/inhibition in cardiomyocytes, adipocytes, and MEFs under certain diseased conditions.

ABSTRACTLaser powder bed fusion (LPBF) of multi-scaled structures is a prominent direction pursued by innovative designs and engineering applications. However, understanding the impact of scale effect on the effectiveness of actual structures is a pressing challenge. This work investigates the influence of structure scale on surface morphology and mechanical property by fabricating tensile samples with gauge diameters ranging from 0.2 mm to 5.0 mm. For the hatching scanning strategy, the surface roughness drastically reduces by ∼51% as the diameter increases. This appears to be the coupling results of heat accumulation, molten pool morphology at the end of single-track, overlap between multi-tracks within a layer, and successive rotational buildup between layers. Moreover, decreasing the diameter substantially reduces the tensile strength. Fortunately, a hatching-contour scanning strategy is proposed to eliminate the scale effect of surface morphology and strength. These efforts provide essential guidance for the broader application of multi-scaled structures.