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Abstract Human social interactions tend to vary in intensity over time, whether they are in person or online. Variable rates of interaction in structured populations can be described by networks with the time-varying activity of links and nodes. One of the key statistics to summarize temporal patterns is the inter-event time, namely the duration between successive pairwise interactions. Empirical studies have found inter-event time distributions that are heavy-tailed, for both physical and digital interactions. But it is difficult to construct theoretical models of time-varying activity on a network that reproduce the burstiness seen in empirical data. Here we develop a spanning-tree method to construct temporal networks and activity patterns with bursty behavior. Our method ensures any desired target inter-event time distributions for individual nodes and links, provided the distributions fulfill a consistency condition, regardless of whether the underlying topology is static or time-varying. We show that this model can reproduce burstiness found in empirical datasets, and so it may serve as a basis for studying dynamic processes in real-world bursty interactions.

Abstract Soft and stretchable electronics have emerged as highly promising tools for biomedical diagnosis and biological studies, as they interface intimately with the human body and other biological systems. Most stretchable electronic materials and devices, however, still have Young’s moduli orders of magnitude higher than soft bio-tissues, which limit their conformability and long-term biocompatibility. Here, we present a design strategy of soft interlayer for allowing the use of existing stretchable materials of relatively high moduli to versatilely realize stretchable devices with ultralow tissue-level moduli. We have demonstrated stretchable transistor arrays and active-matrix circuits with moduli below 10 kPa—over two orders of magnitude lower than the current state of the art. Benefiting from the increased conformability to irregular and dynamic surfaces, the ultrasoft device created with the soft interlayer design realizes electrophysiological recording on an isolated heart with high adaptability, spatial stability, and minimal influence on ventricle pressure. In vivo biocompatibility tests also demonstrate the benefit of suppressing foreign-body responses for long-term implantation. With its general applicability to diverse materials and devices, this soft-interlayer design overcomes the material-level limitation for imparting tissue-level softness to a variety of bioelectronic devices.

Abstract The treatment of myocardial infarction (MI) remains a substantial challenge due to excessive inflammation, massive cell death, and restricted regenerative potential, leading to maladaptive healing process and eventually heart failure. Current strategies of regulating inflammation or improving cardiac tissue regeneration have limited success. Herein, a hybrid hydrogel coassembled by acellular cardiac extracellular matrix (ECM) and immunomodulatory glycopeptide is developed for endogenous tissue regeneration after MI. The hydrogel constructs a niche recapitulating the architecture of native ECM for attracting host cell homing, controlling macrophage differentiation via glycopeptide unit, and promoting endotheliocyte proliferation by enhancing the macrophage‐endotheliocyte crosstalk, which coordinate the innate healing mechanism for cardiac tissue regeneration. In a rodent MI model, the hybrid hydrogel successfully orchestrates a proreparative response indicated by enhanced M2 macrophage polarization, increased angiogenesis, and improved cardiomyocyte survival, which alleviates infarct size, improves wall thicknesses, and enhances cardiac contractility. Furthermore, the safety and effectiveness of the hydrogel are demonstrated in a porcine MI model, wherein proteomics verifies the regulation of immune response, proangiogenesis, and accelerated healing process. Collectively, the injectable composite hydrogel serving as an immunomodulatory niche for promoting cell homing and proliferation, inflammation modulation, tissue remodeling, and function restoration provides an effective strategy for endogenous cardiac repair.

Here, using fecal metagenomics data of 2,320 individuals, the authors develop a microbiome-based machine learning approach showing high accuracy for multi-class disease diagnosis, highlighting its potential application in improving noninvasive diagnostics and monitor responses to therapy.

Here, by performing an integrative multi-omics analysis coupled to clinical features of COVID-19 patients prospectively followed for up to 6 month, the authors identify specific gut microbiome patterns associated with disease severity and development of post-acute COVID-19 syndrome.

The Jinsha River, upstream of the Yangtze River, flows through the southeastern margin of the plateau, providing an opportunity to study the plateau uplift relative to the Sichuan basin through fluvial geomorphology. Eight tributaries of the Jinsha River located at the transition boundary from the plateau to the basin were analyzed for the feature of longitudinal profile and its evolution. The spatial distribution of slope-break knickpoints in the catchment was determined by slope-area analysis and integration analysis. Further, the magnitude and timing of the base level lowering (i.e., uplift of the Tibetan Plateau) were estimated by reconstructing the river longitudinal profile. The results show that there are two levels of slope-break knickpoints, with average elevations of 2865 m and 1523 m, corresponding to base levels relatively lowering of 1400 m and 1100 m, respectively. With reference to the long-term downcutting rate of the Jinsha River, the timings of these two phases base level lowering and uplifts are estimated to be ∼21–24 and ∼7–13 Ma, respectively. These are close to the timing of two uplifts revealed by inversion modeling of river longitudinal profiles. Therefore, the uplift of the studied region on the Tibetan Plateau can be divided into two stages, the early stage (∼20 Ma) uplift from 1500 to 2900 m and the late stage (∼10 Ma) uplift from 2900 to 4000 m, which further supports the staged outside uplift of the Tibetan Plateau.

On 8 January 2022, a seismic event of significant magnitude (Mw 6.7, Ms 6.9) occurred in the northeastern region of the Tibetan Plateau. This earthquake was characterized by left-lateral strike-slip motion, accompanied by a minor reverse movement. The Menyuan earthquake resulted in the formation of two main ruptures and one secondary rupture. These ruptures were marked by a left-lateral step zone that extended over a distance of 1 km between the main ruptures. The length of the rupture zones was approximately 37 km. The surface rupture zone exhibited various features, including left-lateral offset small gullies, riverbeds, wire fences, road subgrades, mole tracks, cracks, and scarps. Through a comprehensive field investigation and precise measurement using unmanned aerial vehicle (UAV) imagery, 111 coseismic horizontal offsets were determined, with the maximum offset recorded at 2.6 ± 0.3 m. The analysis of aftershocks and the findings from the field investigation led to the conclusion that the earthquake was triggered by the Lenglongling fault and the Tuolaishan fault. These faults intersected at a release double-curved structure, commonly referred to as a stepover. During this particular process, the Lenglongling fault was responsible for initiating the coseismic rupture of the Sunan–Qilian fault. It is important to note that the stress applied to the Tuolaishan fault has not been fully relieved, indicating the presence of potential future hazards.

CRISPR-Cas9 is a gene editing tool that can be used to modulate gene expression. Here, the authors report the generation of a mouse model that express all components of the CRISPR-Cas9 guide directed Synergistic Activation Mediator (SAM), demonstrate that gene activation can be achieved with various delivery methods and include generation of a disease model of hypercholesterolemia

Abstract Avian leukosis caused by avian leukosis virus (ALV) is one of the most severe diseases endangering the poultry industry. When the eradication measures performed in commercial broilers and layers have achieved excellent results, ALV in some local chickens has gradually attracted attention. Since late 2018, following the re-outbreak of ALV-J in white feather broilers in China, AL-like symptoms also suddenly broke out in some local flocks, leading to great economic losses. In this study, a systematic epidemiological survey was carried out in eight local chicken flocks in Jiangxi Province, China, and 71 strains were finally isolated from 560 samples, with the env sequences of them being successfully sequenced. All of those new isolates belong to subgroup J but they have different molecular features and were very different from the strains that emerged in white feature broilers recently, with some strains being highly consistent with those previously isolated from commercial broilers, layers and other flocks or even isolated from USA and Russian, suggesting these local chickens have been acted as reservoirs to accumulate various ALV-J strains for a long time. More seriously, phylogenetic analysis shows that there were also many novel strains emerging and in a separate evolutionary branch, indicating several new mutated ALVs are being bred in local chickens. Besides, ALV-J strains isolated in this study can be further divided into ten groups, while there were more or fewer groups in different chickens, revealing that ALV may cross propagate in those flocks. The above analyses explain the complex background and future evolution trend of ALV-J in Chinese local chickens, providing theoretical support for the establishment of corresponding prevention and control measures.

Population structure enables emergence of cooperation among individuals, but the impact of the dynamic nature of real interaction networks is not understood. Here, the authors study the evolution of cooperation on temporal networks and find that temporality enhances the evolution of cooperation.

Summary: Nonalcoholic fatty liver disease (NAFLD) is a global health-care problem with limited therapeutic options. To obtain a cellular resolution of pathogenesis, 82,168 single-cell transcriptomes (scRNA-seq) across different NAFLD stages were profiled, identifying hepatocytes and 12 other non-parenchymal cell (NPC) types. scRNA-seq revealed insights into the cellular and molecular mechanisms of the disease. We discovered a dual role for hepatic stellate cells in gene expression regulation and in the potential to trans-differentiate into myofibroblasts. We uncovered distinct expression profiles of Kupffer cells versus monocyte-derived macrophages during NAFLD progression. Kupffer cells showed stronger immune responses, while monocyte-derived macrophages demonstrated a capability for differentiation. Three chimeric NPCs were identified including endothelial-chimeric stellate cells, hepatocyte-chimeric endothelial cells, and endothelial-chimeric Kupffer cells. Our work identified unanticipated aspects of mouse with NAFLD at the single-cell level and advanced the understanding of cellular heterogeneity in NAFLD livers.

A magnitude (Mw) 7.4 Maduo earthquake occurred on 22 May 2021 in the northern Qinghai-Tibet Plateau, with predominantly left-lateral strike-slip faulting and a component of normal faulting within the Bayan Har Block. The co-seismic surface rupture extended in a NWW direction for ~160 km with a complicated geometry along a poorly known young fault: the Jiangcuo Fault. The main surface rupture propagated bilaterally from the epicenter and terminated eastward in horsetail splays. The main rupture can be divided into five segments with two rupture gaps. Field surveys and detailed mapping revealed that the co-seismic surface ruptures were characterized by a series of left-lateral offsets, en echelon tensional cracks and fissures, compressional mole tracks, and widespread sand liquefication. The observed co-seismic left-lateral displacements ranged from 0.2 m to ~2.6 m, while the vertical displacements ranged from 0.1 m to ~1.5 m, much lower than the InSAR inverse slip maximum of 2–6 m. Based on the comprehensive analysis of the causative fault geometry and the tectonic structure of the northern Bayan Har Block, this study suggests that the multiple NWW trending sub-faults, including the Jiangcuo Fault, developed from the East Kunlun fault northeast of the Bayan Har Block could be regarded as the sub-faults of the East Kunlun Fault system, constituting a broad and dispersive northern boundary of the Block, controlling the inner strain distribution and deformation.

Chitinases are of great importance in chitin degradation and remodeling in insects. However, the genome-wide distribution of chitinase-like gene family in Bemsia tabaci, a destructive pest worldwide, is still elusive. With the help of bioinformatics, we annotated 14 genes that encode putative chitinase-like proteins, including ten chitinases (Cht), three imaginal disk growth factors (IDGF), and one endo-β-N-acetylglucosaminidase (ENGase) in the genome of the whitefly, B. tabaci. These genes were phylogenetically grouped into eight clades, among which 13 genes were classified in the glycoside hydrolase family 18 groups and one in the ENGase group. Afterwards, developmental expression analysis suggested that BtCht10, BtCht5, and BtCht7 were highly expressed in nymphal stages and exhibit similar expression patterns, implying their underlying role in nymph ecdysis. Notably, nymphs exhibited a lower rate of survival when challenged by dsRNA targeting these three genes via a nanomaterial-promoted RNAi method. In addition, silencing of BtCht10 significantly resulted in a longer duration of development compared to control nymphs. These results indicate a key role of BtCht10, BtCht5, and BtCht7 in B. tabaci nymph molting. Our research depicts the differences of chitinase-like family genes in structure and function and identified potential targets for RNAi-based whitefly management.

Previous numerical–analytical approaches have suggested that the main range divide prefers to migrate towards the high uplift flank in the asymmetric tectonic uplift pattern. However, natural examples recording these processes and further verifying the numerical simulations results, are still lacking. In this study, the landscape features, and the probable drainage evolution history of the Zhongtiao Shan, a roughly west-east trending, half-horst block on the southernmost tip of the Shanxi Graben System, were investigated through the geomorphic analyses (i.e., slope and steepness distributions, and the Gilbert and χ metrics). The topographic slope and steepness results indicate that the Zhongtiao Shan, controlled by the north Zhongtiao Shan normal fault, experiences asymmetric uplift and erosion patterns, with higher uplift and erosion on the north range. In addition, the Gilbert and χ metrics suggest that the western part of the main divide is currently stable, while the eastern divide is moving southward. According to the drainage divide stability criteria, we suggest that the uplift and erosion, on the fault side, balance each other well on the western part of the range, while on the eastern part, the uplift is outpaced by the erosion. In addition, a dynamic divide migration model in the asymmetric uplift condition is proposed, indicating that the interaction between uplift and erosion controls the migration and/or stability of the main divide. Deducing through this dynamic model, we suggested that the eastern segment of the north Zhongtiaoshan Fault must have experienced higher activities in the geological history, and the western fault may remain its activity along with the mountain relief generation. This gives a case that specific information on asymmetric neotectonic history and landscape evolution in an orogenic mountain can be uncovered by the proposed dynamic model.

It is well-known that the effects of spatial selection on the two-strategy competition can be quantified by the structural coefficient σ under weak selection. We here calculate the accurate value of σ in group-structured populations of any finite size. In previous similar models, the large population size has been explicitly required for obtaining σ, and here we analyze quantitatively how large the population should be. Unlike previous models which have only involved the influences of the longest and the shortest migration rang on σ, we consider all migration ranges together. The new phenomena are that an intermediate range maximizes σ for medium migration probabilities which are of the tiny minority and the maximum value is slightly larger than those for other ranges. Furthermore, we find the ways that migration or mutation changes σ can vary significantly through determining analytically how the high-frequency steady states (distributions of either strategy over all groups) impact the expression of σ obtained before. Our findings can be directly used to resolve the dilemma of cooperation and provide a more intuitive understanding of spatial selection.

Interspecific competition between herbivores is widely recognized as an important determinant of community structure. Although researchers have identified a number of factors capable of altering competitive interactions, few studies have addressed the influence of neighboring plant species. If adaptation to/ epigenetic effects of an herbivore's natal host plant alter its performance on other host plants, then interspecific herbivore interactions may play out differently in heterogeneous and homogenous plant communities. We tested wether the natal host plant of a whitefly population affected interactions between the Middle-east Asia Minor 1 (MEAM1) and Mediterranean (MED) cryptic species of the whitefly Bemisia tabaci by rearing the offspring of a cabbage-derived MEAM1 population and a poinsettia-derived MED population together on three different host plants: cotton, poinsettia, and cabbage. We found that MED dominated on poinsettia and that MEAM1 dominated on cabbage, results consistent with previous research. MED also dominated when reared with MEAM1 on cotton, however, a result at odds with multiple otherwise-similar studies that reared both species on the same natal plant. Our work provides evidence that natal plants affect competitive interactions on another plant species, and highlights the potential importance of neighboring plant species on herbivore community composition in agricultral systems.

Cooperation abounds in all biological systems. Spatial public goods game (PGG) serves as a baseline model when investigating the evolution of cooperation in collective interactions. Since analyzing collective interactions and dynamics in spatial structures is very complicated, a full theoretical understanding of spatial PGGs is still deficient. Here we generalize spatial PGGs in a three-layer weighted network—investment, benefit allocation, and strategy dispersal layers—which are not necessarily identical and thus cover a wide class of population structures and interaction scenarios. We provide an analytic formula that accurately predicts when cooperation is favored over defection, and that is applicable in populations of any size under weak selection. We prove that in regular networks investment and benefit allocation are essentially symmetric—that exchanging structures of investment and benefit allocation layers does not affect the evolutionary dynamics at all. The success of cooperators relies heavily on the correlation between an individual’s investment in a game and its benefit allocated from the same game. In most cases, the positive correlation, i.e., a greater investment in games with a larger share of benefits, facilitates a cooperative society. Importantly, we also show that diversifying the amounts of investment in different games or benefit allocation to different participants, if implementing improperly, might impede the global cooperation.

As evidenced by many cases in human societies, individuals often make different behavior decisions in different interactions, and adaptively adjust their behavior in changeable interactive scenarios. However, up to now, how such diverse interactive behavior affects cooperation dynamics has still remained unknown. Here we develop a general framework of interactive diversity, which models individuals’ separated behavior against distinct opponents and their adaptive adjustment in response to opponents’ strategies, to explore the evolution of cooperation. We find that interactive diversity enables individuals to reciprocate every single opponent, and thus sustains large-scale reciprocal interactions. Our work witnesses an impressive boost of cooperation for a notably extensive range of parameters and for all pairwise games. These results are robust against well-mixed and various networked populations, and against degree-normalized and cumulative payoff patterns. From the perspective of network dynamics, distinguished from individuals competing for nodes in most previous work, in this paper, the system evolves in the form of behavior disseminating along edges. We propose a theoretical method based on evolution of edges, which predicts well both the frequency of cooperation and the compact cooperation clusters. Our thorough investigation clarifies the positive role of interactive diversity in resolving social dilemmas and highlights the significance of understanding evolutionary dynamics from the viewpoint of edge dynamics.

The whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) harbors several bacterial symbionts. Among the secondary (facultative) symbionts, Hamiltonella has high prevalence and high infection frequencies, suggesting that it may be important for the biology and ecology of its hosts. Previous reports indicated that Hamiltonella increases whitefly fitness and, based on the complete sequencing of its genome, may have the ability to synthesize cofactors and amino acids that are required by its host but that are not sufficiently synthesized by the host or by the primary endosymbiont, Portiera. Here, we assessed the effects of Hamiltonella infection on the growth of B. tabaci reared on low-, standard-, or high-nitrogen diets. When B. tabaci was reared on a standard-nitrogen diet, no cost or benefit was associated with Hamiltonella infection. But, if we reared whiteflies on low-nitrogen diets, Hamiltonella-infected whiteflies often grew better than uninfected whiteflies. Furthermore, nitrogen levels in field-collected whiteflies indicated that the nutritional conditions in the field were comparable to the low-nitrogen diet in our laboratory experiment. These data suggest that Hamiltonella may play a previously unrecognized role as a nutritional mutualist in B. tabaci.

Bacterial symbionts often enhance the physiological capabilities of their arthropod hosts and enable their hosts to expand into formerly unavailable niches, thus leading to biological diversification. Many arthropods, including the worldwide invasive whitefly Bemisia tabaci, have individuals simultaneously infected with symbionts of multiple genera that occur in different locations in the host. This study examined the population dynamics of symbionts that are located in different areas within B. tabaci. While densities of Portiera and Hamiltonella (which are located in bacteriocytes) appeared to be well-regulated during host development, densities of Rickettsia (which are not located in bacteriocytes) were highly variable among individual hosts during host development. Host mating did not significantly affect symbiont densities. Infection by Tomato yellow leaf curl virus did not affect Portiera and Hamiltonella densities in either sex, but increased Rickettsia densities in females. High and low temperatures did not affect Portiera and Hamiltonella densities, but low temperature (15 °C) significantly suppressed Rickettsia densities whereas high temperature (35 °C) had little effect on Rickettsia densities. The results are consistent with the view that the population dynamics of bacterial symbionts in B. tabaci are regulated by symbiont location within the host and that the regulation reflects adaptation between the bacteria and insect.

Evolutionary games on networks traditionally assume that each individual adopts an identical strategy to interact with all its neighbors in each generation. Considering the prevalent diversity of individual interactions in the real society, here we propose the concept of interactive diversity, which allows individuals to adopt different strategies against different neighbors in each generation. We investigate the evolution of cooperation based on the edge dynamics rather than the traditional nodal dynamics in networked systems. The results show that, without invoking any other mechanisms, interactive diversity drives the frequency of cooperation to a high level for a wide range of parameters in both well-mixed and structured populations. Even in highly connected populations, cooperation still thrives. When interactive diversity and large topological heterogeneity are combined together, however, in the relaxed social dilemma, cooperation level is lower than that with just one of them, implying that the combination of many promotive factors may make a worse outcome. By an analytical approximation, we get the condition under which interactive diversity provides more advantages for cooperation than traditional evolutionary dynamics does. Numerical simulations validating the approximation are also presented. Our work provides a new line to explore the latent relation between the ubiquitous cooperation and individuals’ distinct responses in different interactions. The presented results suggest that interactive diversity should receive more attention in pursuing mechanisms fostering cooperation.

BACKGROUND: Bemisia tabaci (Gennadius) is a phloem-feeding insect poised to become one of the major insect pests in open field and greenhouse production systems throughout the world. The high level of resistance to insecticides is a main factor that hinders continued use of insecticides for suppression of B. tabaci. Despite its prevalence, little is known about B. tabaci at the genome level. To fill this gap, an invasive B. tabaci B biotype was subjected to pyrosequencing-based transcriptome analysis to identify genes and gene networks putatively involved in various physiological and toxicological processes. METHODOLOGY AND PRINCIPAL FINDINGS: Using Roche 454 pyrosequencing, 857,205 reads containing approximately 340 megabases were obtained from the B. tabaci transcriptome. De novo assembly generated 178,669 unigenes including 30,980 from insects, 17,881 from bacteria, and 129,808 from the nohit. A total of 50,835 (28.45%) unigenes showed similarity to the non-redundant database in GenBank with a cut-off E-value of 10-5. Among them, 40,611 unigenes were assigned to one or more GO terms and 6,917 unigenes were assigned to 288 known pathways. De novo metatranscriptome analysis revealed highly diverse bacterial symbionts in B. tabaci, and demonstrated the host-symbiont cooperation in amino acid production. In-depth transcriptome analysis indentified putative molecular markers, and genes potentially involved in insecticide resistance and nutrient digestion. The utility of this transcriptome was validated by a thiamethoxam resistance study, in which annotated cytochrome P450 genes were significantly overexpressed in the resistant B. tabaci in comparison to its susceptible counterparts. CONCLUSIONS: This transcriptome/metatranscriptome analysis sheds light on the molecular understanding of symbiosis and insecticide resistance in an agriculturally important phloem-feeding insect pest, and lays the foundation for future functional genomics research of the B. tabaci complex. Moreover, current pyrosequencing effort greatly enriched the existing whitefly EST database, and makes RNAseq a viable option for future genomic analysis.

BACKGROUND: Tomato yellow leaf curl virus (TYLCV) was introduced into China in 2006, approximately 10 years after the introduction of an invasive whitefly, Bemisia tabaci (Genn.) B biotype. Even so the distribution and prevalence of TYLCV remained limited, and the economic damage was minimal. Following the introduction of Q biotype into China in 2003, the prevalence and spread of TYLCV started to accelerate. This has lead to the hypothesis that the two biotypes might not be equally competent vectors of TYLCV. METHODOLOGY/PRINCIPAL FINDINGS: The infection frequency of TYLCV in the field-collected B. tabaci populations was investigated, the acquisition and transmission capability of TYLCV by B and Q biotypes were compared under the laboratory conditions. Analysis of B. tabaci populations from 55 field sites revealed the existence of 12 B and 43 Q biotypes across 18 provinces in China. The acquisition and transmission experiments showed that both B and Q biotypes can acquire and transmit the virus, however, Q biotype demonstrated superior acquisition and transmission capability than its B counterparts. Specifically, Q biotype acquired significantly more viral DNA than the B biotype, and reached the maximum viral load in a substantially shorter period of time. Although TYLCV was shown to be transmitted horizontally by both biotypes, Q biotype exhibited significantly higher viral transmission frequency than B biotype. Vertical transmission result, on the other hand, indicated that TYLCV DNA can be detected in eggs and nymphs, but not in pupae and adults of the first generation progeny. CONCLUSIONS/SIGNIFICANCE: These combined results suggested that the epidemiology of TYLCV was aided differentially by the two invasive whiteflies (B and Q biotypes) through horizontal but not vertical transmission of the virus. This is consistent with the concomitant eruption of TYLCV in tomato fields following the recent rapid invasion of Q biotype whitefly in China.

Abstract Efficient energy conversion using ions as carriers necessitates membranes that sustain high permselectivity in high salinity conditions, which presents a significant challenge. This study addresses the issue by manipulating the linkages in covalent-organic-framework membranes, altering the distribution of electrostatic potentials and thereby influencing the short-range interactions between ions and membranes. We show that a charge-neutral covalent-organic-framework membrane with β-ketoenamine linkages achieves record permselectivity in high salinity environments. Additionally, the membrane retains its permselectivity under temperature gradients, providing a method for converting low-grade waste heat into electrical energy. Experiments reveal that with a 3 M KCl solution and a 50 K temperature difference, the membrane generates an output power density of 5.70 W m−2. Furthermore, guided by a short-range ionic screening mechanism, the membrane exhibits adaptable permselectivity, allowing reversible and controllable operations by finely adjusting charge polarity and magnitude on the membrane’s channel surfaces via ion adsorption. Notably, treatment with K3PO4 solutions significantly enhances permselectivity, resulting in a giant output power density of 20.22 W m−2, a 3.6-fold increase over the untreated membrane, setting a benchmark for converting low-grade heat into electrical energy.

Abstract Neutrophil infiltration plays a key role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, pertinent mechanisms remain poorly elucidated. Here, we obtained the data from gene expression omnibus (GEO) and gene set enrichment analysis (GSEA) to identify and validate neutrophil-associated hub genes in CRSwNP. We found that four neutrophil-associated hub genes, namely ICAM1, IL-1β, TYROBP, and BCL2A1, were markedly upregulated and positively correlated with neutrophil infiltration levels in patients with CRSwNP. Subsequently, this was confirmed by real-time quantitative PCR. In conclusion, we identified the role of neutrophil infiltration in the pathophysiology of CRSwNP, which may be the potential targets for the diagnosis and treatment of CRSwNP.

Abstract Membrane reactors are known for their efficiency and superior operability compared to traditional batch processes, but their limited diversity poses challenges in meeting various reaction requirements. Herein, we leverage the molecular tunability of covalent organic frameworks (COFs) to broaden their applicability in membrane reactors. Our COF membrane demonstrates an exceptional ability to achieve complete conversion in just 0.63 s at room temperature—a benchmark in efficiency for Knoevenagel condensation. This performance significantly surpasses that of the corresponding homogeneous catalyst and COF powder by factors of 176 and 375 in turnover frequency, respectively. The enhanced concentration of reactants and the rapid removal of generated water within the membrane greatly accelerate the reaction, reducing the apparent activation energy. Consequently, this membrane reactor enables reactions that are unattainable using both COF powders and homogeneous catalysts. Considering the versatility, our findings highlight the substantial promise of COF-based membrane reactors in organic transformations.

Abstract Parkinson’s disease (PD) and inflammatory bowel disease (IBD) are chronic diseases affecting the central nervous system and gastrointestinal tract, respectively. Recent research suggests a bidirectional relationship between neurodegeneration in PD and intestinal inflammation in IBD. PD patients may experience gastrointestinal dysfunction over a decade before motor symptom onset, and IBD may increase the risk of developing PD. Despite the “gut-brain axis” concept, the underlying pathophysiological mechanisms of this potential association remain unclear. This study aimed to investigate the biological mechanisms of differentially expressed genes in PD and IBD using bioinformatics tools, providing novel insights into the co-diagnosis and treatment of these diseases. We constructed a gene marker for disease diagnosis and identified five important genes (BTK, NCF2, CRH, FCGR3A and SERPINA3). Through nomogram and decision tree analyses, we found that both the IBD and PD required only the expression levels of BTK and NCF2 for accurate discrimination. Additionally, small molecule drugs RO-90-7501 and MST-312 may be useful for the treatment of both IBD and PD. These findings offer new perspectives on the co-diagnosis and treatment of PD and IBD, and suggest that targeting BTK may be a promising therapeutic strategy for both diseases.

Summary: Major depressive disorder (MDD) is a prevalent mental disorder with serious impacts on life and health. Neuroimaging offers valuable diagnostic insights. However, traditional computer-aided diagnosis methods are limited by reliance on researchers’ experience. To address this, we proposed an evolutionary neural architecture search (M-ENAS) framework for automatically diagnosing MDD using multi-modal magnetic resonance imaging (MRI). M-ENAS determines the optimal weight and network architecture through a two-stage search method. Specifically, we designed a one-shot network architecture search (NAS) strategy to train supernet weights and a self-defined evolutionary search to optimize the network structure. Finally, M-ENAS was evaluated on two datasets, demonstrating that M-ENAS outperforms existing hand-designed methods. Additionally, our findings reveal that brain regions within the somatomotor network play important roles in the diagnosis of MDD, providing additional insight into the biological mechanisms underlying the disorder.

Summary: Kidney fibrosis marks a critical phase in chronic kidney disease with its molecular intricacies yet to be fully understood. This study’s deep dive into single-cell sequencing data of renal tissue during fibrosis pinpoints the pivotal role of fibroblasts and myofibroblasts in the fibrotic transformation. Through identifying distinct cell populations and conducting transcriptomic analysis, Spp1 emerged as a key gene associated with renal fibrosis. The study’s experimental findings further confirm Spp1’s vital function in promoting fibroblast to myofibroblast differentiation via the TGF-β/Smad signaling pathway, underscoring its contribution to fibrosis progression. The suppression of Spp1 expression notably hindered this differentiation process, spotlighting Spp1 as a promising therapeutic target for halting renal fibrosis. This condensed summary encapsulates the essence and findings of the original research within the specified word limit.

Examination of bacteria/host cell interactions is important for understanding the aetiology of many infectious diseases. The colony forming unit (CFU) has been the standard for quantifying bacterial burden for the past century, however, this suffers from low sensitivity and is dependent on bacterial culturability in vitro. Our data demonstrate the discrepancy between the CFU and bacterial genome copy number in an osteomyelitis-relevant co-culture system and we confirm diagnosis and quantify bacterial load in clinical bone specimens. This study provides an improved workflow for the quantification of bacterial burden in such cases.

The Eocene was a typical greenhouse climate period in the history of the Earth, with a high global sea level and extensive carbonate deposits developed in Tethys. During the Eocene, a carbonate platform was deposited in the western Tarim Basin, which belongs to the easternmost Tethys. However, the details of this carbonate platform and its complications for paleoecology and paleoclimate are still unclear. This research focuses on the bivalve-bearing carbonates of the Kalataer Formation in the western Tarim Basin, and detailed analyses of microfacies, biostratigraphy, paleoecology, and sea-level change were carried out. The bivalves of the Kalataer Formation are dominated by the Ostrea (Turkostrea) strictiplicata, Ostrea (Turkostrea) cizancourti, Ostrea (Turkostrea) strictiplicata, Ostrea (Turkostrea) strictiplicata, and Sokolowia buhsii, and the age is middle Lutetian of the Eocene. The biota of the Kalataer Formation mainly lives in open shallow sea environments, with medium to low energy and rich nutrients and oxygen, representing a typical shallow marine ecosystem of the carbonate platform. Microfacies and paleoecology indicate a large marine transgression event occurred in the western Tarim Basin during the middle Eocene.

Recurrent joint bleeding in hemophilia patients frequently causes hemophilic arthropathy (HA). Drastic degradation of cartilage is a major characteristic of HA, but its pathological mechanisms has not yet been clarified. In HA cartilages, we found server matrix degradation and increased expression of DNA methyltransferase proteins. We thus performed genome-wide DNA methylation analysis on human HA (N=5) and osteoarthritis (OA) (N=5) articular cartilages, and identified 1228 differentially methylated regions (DMRs) associated with HA. Functional enrichment analyses revealed the association between DMR genes (DMGs) and extracellular matrix (ECM) organization. Among these DMGs, Tenascin XB (TNXB) expression was down-regulated in human and mouse HA cartilages. The loss of Tnxb in F8-/- mouse cartilage provided a disease-promoting role in HA by augmenting cartilage degeneration and subchondral bone loss. Tnxb knockdown also promoted chondrocyte apoptosis and inhibited phosphorylation of AKT. Importantly, AKT agonist showed chondroprotective effects following Tnxb knockdown. Together, our findings indicate that exposure of cartilage to blood leads to alterations in DNA methylation, which is functionally related to ECM homeostasis, and further demonstrate a critical role of TNXB in HA cartilage degeneration by activating AKT signaling. These mechanistic insights allow development of potentially new strategies for HA cartilage protection.

Abstract Recent studies have found that the estimates of motion directions are biased toward the previous form orientations, showing serial dependence, and the serial dependence does not involve cognitive abilities. In the current study, we conducted two experiments to investigate whether and how attention—a cognitive ability—affected the serial dependence. The results showed that serial dependence was present in the current study, reproducing the previous findings. Importantly, when the attentional load reduced the reliability (i.e., estimation accuracy and precision) of previous form orientations (Experiment 1), the serial dependence decreased, meaning that the biases of motion direction estimates toward previous form orientations were reduced; in contrast, when the attentional load reduced the reliability of current motion directions (Experiment 2), the serial dependence increased, meaning that the biases of motion direction estimates toward previous form orientations were increased. These trends were well consistent with the prediction of the Bayesian inference theory. Therefore, the current study revealed the involvement of attention in the serial dependence of current motion direction estimation on the previous form orientation, demonstrating that the serial dependence was cognitive and the attentional effect can be a Bayesian inference process, initially revealing its computational mechanism.

Abstract Highly stretchable porous materials are promising for flexible electronics but their fabrication is a great challenge. Herein, several kinds of highly stretchable conductive porous elastomers with low or negative Poisson’s ratios are achieved by uniaxial, biaxial, and triaxial hot-pressing strategies. The reduced graphene oxide/polymer nanocomposite elastomers with folded porous structures obtained by uniaxial hot pressing exhibit high stretchability up to 1200% strain. Furthermore, the meta-elastomers with reentrant porous structures combining high biaxial (or triaxial) stretchability and negative Poisson’s ratios are achieved by biaxial (or triaxial) hot pressing. The resulting elastomer-based wearable strain sensors exhibit an ultrawide response range (0-1200%). The materials can be applied for smart thermal management and electromagnetic interference shielding, which are achieved by regulating the porous microstructures via stretching. This work provides a versatile strategy to highly stretchable and negative-Poisson-ratio porous materials with promising features for various applications such as flexible electronics, thermal management, electromagnetic shielding, and energy storage.

Abstract The incorporation of crown ether into metal‐organic frameworks (MOFs) is garnered significant attention because these macrocyclic units can fine‐tune the inherent properties of the frameworks. However, the synthesis of flexible crown ethers with precise structures as the fundamental building blocks of crystalline MOFs remains a challenging endeavor, with only a limited number of transition metal examples existing to date. Herein, 18‐crown‐6 and 24‐crown‐8 struts are successfully incorporated into the skeleton of zirconium‐based MOFs to obtain two new and stable crown ether‐based MOFs, denoted as ZJU‐X100 and ZJU‐X102. These newly developed MOFs displayed high porosity and remarkable stability when exposed to various solvents, boiling water, pH values, and even concentrated HCl conditions. Thanks to their highly ordered porous structure and high‐density embedding of specific binding sites within tubular channels, these two MOFs exhibited extremely fast sorption kinetics and demonstrated outstanding performance in the uptake of strontium and cesium ions, respectively. Furthermore, the structures of Sr‐adsorbed ZJU‐X100 and Cs‐adsorbed ZJU‐X102 are solved and confirmed the precise location of Sr2+/Cs+ in the cavity of 18‐crown‐6/24‐crown‐8. This makes modular mosaic of different crown ethers into the skeleton of stable zirconium‐based MOFs possible and promote such materials have broad applications in sorption, sensing, and catalysis.

Summary: Many studies have demonstrated that attention affects the perception of many visual features. However, previous studies show conflicting results regarding the effect of attention on the perception of self-motion direction (i.e., heading) from optic flow. To address this question, we conducted three behavioral experiments and found that estimation accuracies of large headings (>14°) decreased with attention load, discrimination thresholds of these headings increased with attention load, and heading estimates were systematically compressed toward the focus of attention. Therefore, the current study demonstrated that attention affected heading perception from optic flow, showing that the perception is both information-driven and cognitive.

Abstract The effective management of osteomyelitis remains extremely challenging due to the difficulty associated with treating bone defects, the high probability of recurrence, the requirement of secondary surgery or multiple surgeries, and the difficulty in eradicating infections caused by methicillin‐resistant Staphylococcus aureus (MRSA). Hence, smart biodegradable biomaterials that provide effective and precise local anti‐infection effects and can promote the repair of bone defects are actively being developed. Here, a novel nano‐micro composite is fabricated by combining calcium phosphate (CaP) nanosheets with drug‐loaded GelMA microspheres via microfluidic technology. The microspheres are covalently linked with vancomycin (Van) through an oligonucleotide (oligo) linker using an EDC/NHS carboxyl activator. Accordingly, a smart nano‐micro composite called “CaP@MS‐Oligo‐Van” is synthesized. The porous CaP@MS‐Oligo‐Van composites can target and capture bacteria. They can also release Van in response to the presence of bacterial micrococcal nuclease and Ca2+, exerting additional antibacterial effects and inhibiting the inflammatory response. Finally, the released CaP nanosheets can promote bone tissue repair. Overall, the findings show that a rapid, targeted drug release system based on CaP@MS‐Oligo‐Van can effectively target bone tissue infections. Hence, this agent holds potential in the clinical treatment of osteomyelitis caused by MRSA.

Abstract Access to sustainable energy is paramount in today’s world, with a significant emphasis on solar and water-based energy sources. Herein, we develop photo-responsive ionic dye-sensitized covalent organic framework membranes. These innovative membranes are designed to significantly enhance selective ion transport by exploiting the intricate interplay between photons, electrons, and ions. The nanofluidic devices engineered in our study showcase exceptional cation conductivity. Additionally, they can adeptly convert light into electrical signals due to photoexcitation-triggered ion movement. Combining the effects of salinity gradients with photo-induced ion movement, the efficiency of these devices is notably amplified. Specifically, under a salinity differential of 0.5/0.01 M NaCl and light exposure, the device reaches a peak power density of 129 W m−2, outperforming the current market standard by approximately 26-fold. Beyond introducing the idea of photoelectric activity in ionic membranes, our research highlights a potential pathway to cater to the escalating global energy needs.

Abstract In this study, the strength characteristics, deformation characteristics and damage characteristics of three kinds of specimens, namely, surrounding rock, cemented paste backfill (CPB) and a surrounding rock-CPB combination, were studied by uniaxial compression testing using rice husk ash and slag as cementing materials, and the mechanical properties of the combination specimens with different height ratios were also analyzed. The results showed that the surrounding rock specimens were the strongest, followed by the composite body, and the CPB was the weakest. The relationship between different height ratios of the assemblage and the cut line modulus was found according to the fitted curves. The CPB specimens and the surrounding rock specimens showed ductile damage, while the assemblage specimens showed brittle damage.

Abstract Experimental studies reported biochemical actions underpinning aging processes and mortality, but the relevant metabolic alterations in humans are not well understood. Here we examine the associations of 243 plasma metabolites with mortality and longevity (attaining age 85 years) in 11,634 US (median follow-up of 22.6 years, with 4288 deaths) and 1878 Spanish participants (median follow-up of 14.5 years, with 525 deaths). We find that, higher levels of N2,N2-dimethylguanosine, pseudouridine, N4-acetylcytidine, 4-acetamidobutanoic acid, N1-acetylspermidine, and lipids with fewer double bonds are associated with increased risk of all-cause mortality and reduced odds of longevity; whereas L-serine and lipids with more double bonds are associated with lower mortality risk and a higher likelihood of longevity. We further develop a multi-metabolite profile score that is associated with higher mortality risk. Our findings suggest that differences in levels of nucleosides, amino acids, and several lipid subclasses can predict mortality. The underlying mechanisms remain to be determined.

Abstract Intrinsically disordered proteins (IDPs) play crucial roles in cellular processes and hold promise as drug targets. However, the dynamic nature of IDPs remains poorly understood. Here, we construct a single-molecule electrical nanocircuit based on silicon nanowire field-effect transistors (SiNW-FETs) and functionalize it with an individual disordered c-Myc bHLH-LZ domain to enable label-free, in situ, and long-term measurements at the single-molecule level. We use the device to study c-Myc interaction with Max and/or small molecule inhibitors. We observe the self-folding/unfolding process of c-Myc and reveal its interaction mechanism with Max and inhibitors through ultrasensitive real-time monitoring. We capture a relatively stable encounter intermediate ensemble of c-Myc during its transition from the unbound state to the fully folded state. The c-Myc/Max and c-Myc/inhibitor dissociation constants derived are consistent with other ensemble experiments. These proof-of-concept results provide an understanding of the IDP-binding/folding mechanism and represent a promising nanotechnology for IDP conformation/interaction studies and drug discovery.

Abstract Studying human dietary intake may help us identify effective measures to treat or prevent many chronic diseases whose natural histories are influenced by nutritional factors. Here, by examining five cohorts with dietary intake data collected on different time scales, we show that the food intake profile varies substantially across individuals and over time, while the nutritional intake profile appears fairly stable. We refer to this phenomenon as ‘nutritional redundancy’ and attribute it to the nested structure of the food-nutrient network. This network enables us to quantify the level of nutritional redundancy for each diet assessment of any individual. Interestingly, this nutritional redundancy measure does not strongly correlate with any classical healthy diet scores, but its performance in predicting healthy aging shows comparable strength. Moreover, after adjusting for age, we find that a high nutritional redundancy is associated with lower risks of cardiovascular disease and type 2 diabetes.

Abstract Photoacoustic tomography (PAT), also known as optoacoustic tomography, is an attractive imaging modality that provides optical contrast with acoustic resolutions. Recent progress in the applications of PAT largely relies on the development and employment of ultrasound sensor arrays with many elements. Although on-chip optical ultrasound sensors have been demonstrated with high sensitivity, large bandwidth, and small size, PAT with on-chip optical ultrasound sensor arrays is rarely reported. In this work, we demonstrate PAT with a chalcogenide-based micro-ring sensor array containing 15 elements, while each element supports a bandwidth of 175 MHz (−6 dB) and a noise-equivalent pressure of 2.2 mPaHz−1/2. Moreover, by synthesizing a digital optical frequency comb (DOFC), we further develop an effective means of parallel interrogation to this sensor array. As a proof of concept, parallel interrogation with only one light source and one photoreceiver is demonstrated for PAT with this sensor array, providing images of fast-moving objects, leaf veins, and live zebrafish. The superior performance of the chalcogenide-based micro-ring sensor array and the effectiveness of the DOFC-enabled parallel interrogation offer great prospects for advancing applications in PAT.

Abstract Matrix assisted laser desorption/ionization imaging has greatly improved our understanding of spatial biology, however a robust bioinformatic pipeline for data analysis is lacking. Here, we demonstrate the application of high-dimensionality reduction/spatial clustering and histopathological annotation of matrix assisted laser desorption/ionization imaging datasets to assess tissue metabolic heterogeneity in human lung diseases. Using metabolic features identified from this pipeline, we hypothesize that metabolic channeling between glycogen and N-linked glycans is a critical metabolic process favoring pulmonary fibrosis progression. To test our hypothesis, we induced pulmonary fibrosis in two different mouse models with lysosomal glycogen utilization deficiency. Both mouse models displayed blunted N-linked glycan levels and nearly 90% reduction in endpoint fibrosis when compared to WT animals. Collectively, we provide conclusive evidence that lysosomal utilization of glycogen is required for pulmonary fibrosis progression. In summary, our study provides a roadmap to leverage spatial metabolomics to understand foundational biology in pulmonary diseases.

Quinidine has been used as an anticonvulsant to treat patients with KCNT1-related epilepsy by targeting gain-of-function KCNT1 pathogenic mutant variants. However, the detailed mechanism underlying quinidine’s blockade against KCNT1 (Slack) remains elusive. Here, we report a functional and physical coupling of the voltage-gated sodium channel NaV1.6 and Slack. NaV1.6 binds to and highly sensitizes Slack to quinidine blockade. Homozygous knockout of NaV1.6 reduces the sensitivity of native sodium-activated potassium currents to quinidine blockade. NaV1.6-mediated sensitization requires the involvement of NaV1.6’s N- and C-termini binding to Slack’s C-terminus and is enhanced by transient sodium influx through NaV1.6. Moreover, disrupting the Slack-NaV1.6 interaction by viral expression of Slack’s C-terminus can protect against SlackG269S-induced seizures in mice. These insights about a Slack-NaV1.6 complex challenge the traditional view of ‘Slack as an isolated target’ for anti-epileptic drug discovery efforts and can guide the development of innovative therapeutic strategies for KCNT1-related epilepsy.