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Abstract To evaluate the effectiveness and biocompatibility of Wistend, a novel Schlemm’s canal (SC) microstent made of Nitinol designed to improve aqueous humor outflow. New Zealand white (NZW) rabbits were divided into blank, sham-operated and Wistend groups. ICare® Tonovet Plus®, swept-source optical coherence tomography (SS-OCT), slit lamp biomicroscopy, retinal camera and scanning electron microscopy (SEM) were used for preoperative and postoperative observations. Hematoxylin and Eosin (H&E) tissue staining was adopted for biocompatibility. A significant difference in intraocular pressure (IOP) between the Wistend group and the control groups was observed during the six-month follow-up. SS-OCT identified arc line internal reflections within the SC in the anterior chamber angle. Conjunctival congestion and edema gradually diminished in the early stages. No corneal vascularization, no anterior chamber inflammatory response and no significant tissue reactions were noted in any groups. SEM showed the Wistend’s windows and orifices remained clear, encircled by minimal incidental ocular tissue and free from blockage. Histopathological examination revealed no discernible differences between the Wistend-implanted and sham-operated eyes. These in vivo studies demonstrate the effectiveness and biocompatibility of the microstent. Our findings suggest a promising potential for Wistend in significantly reducing IOP and effectively facilitating the outflow of aqueous humor.

Abstract Background Professional commitment of nursing students is closely related to the stability of the nursing team. Personality traits and metacognition may be related to professional commitment. We investigate the association between Big Five personality, metacognition, and professional commitment among nursing students, and further explore whether Big Five personality modifies the association between metacognition and professional commitment. Methods From December 2023 to January 2024, a cross-sectional study was conducted among 3631 nursing students from 17 universities in China through the online platform Sojump.com by cluster sampling method and using the general information questionnaire, BFI-44 (Big Five Inventory 44) scale, metacognition scale and professional commitment scale to investigate their demographic data, personality traits, level of metacognition and level of professional commitment. Latent profile analysis was employed to identify optimal categories of personality traits. Multivariate logistic regression was used to analyze the association between the personality traits and professional commitment, as well as metacognition and professional commitment in all participants and participants with different personality traits subgroups, adjusting for potential covariates. Furthermore, the potential mediating role of metacognition between personality traits and professional commitment was also investigated. Results Three distinct personality traits were identified: sensitive-negative personality (65.2%), ordinary personality (26.6%), and open-positive personality (8.2%). Compared with nursing students with sensitive-negative personality, nursing students with ordinary personality and open-positive personality were associated with professional commitment, respectively [OR (95% CI): 7.01 (5.99–8.20), 21.09 (15.43–28.83)]. The p value for trend of personality and professional commitment was

Abstract Recent research has uncovered a surprisingly high occurrence of aberrant expression and mutations in the genes that encode subunits of the SWI/SNF chromatin-remodeling complexes (SCRC). Nevertheless, the carcinogenic effects of aberrant expression and mutations in SWI/SNF genes have only been acknowledged in recent times, resulting in a comparatively limited understanding of these modifications. In this study, we comprehensively analyzed the expression difference, somatic mutation, potential biological pathways, stromal or immune cell infiltration, and drug sensitivity of SCRC-related genes (SCRGs) in pan-cancer. Furthermore, the evolutionary trend, prognostic signature, and immunotherapy response of SCRGs in kidney renal clear cell carcinoma (KIRC) were also evaluated. The expression of SCRGs was changed in 13 out of 14 tumor types, strongly linked to prognosis, and mutated in 30.9% of tumor patients. SCRGs were also closely associated with immune-related pathways and tumor metastasis pathways. The expression of SCRGs was positively associated with the immune score or stromal score but negatively correlated with Tumor purity. Three potential drugs (FK866, Ispinesib mesylate, and WZ3105) were identified to target the SCRGs. In KIRC, scRNA-seq analysis showed that the enrichment of SCRC and the communication frequency with immune cells were significantly declined during tumor cell progression. A prognostic signature was constructed in KIRC and was effective in predicting the prognosis for KIRC. Aberrant expression of eleven prognostic genes identified from the KIRC prognostic signature and the cytotoxicity of FK866 and Ispinesib mesylate to KIRC were verified by qRT-PCR and CCK-8 assay, respectively. Our study identified SCRGs as potential biomarker and therapeutic targets, providing new insights into SCRC for tumor-targeted therapy.

Abstract Meniscus-derived stem cells (MeSCs), a unique type of MSC, have outstanding advantages in meniscal cytotherapy and tissue engineering, but the effects and molecular mechanisms of PBM on MeSCs are still unclear. We used 660-nm LED light with different energy densities to irradiate six human MeSC samples and tested their proliferation rate via cell counting, chondrogenic differentiation capacity via the DMMB assay, mitochondrial activity via the MTT assay, and gene expression via qPCR. The proliferation ability, chondrogenic capacity and mitochondrial activity of the 18 J/cm2 group were greater than those of the 4 J/cm2 and control groups. The mRNA expression levels of Akt, PI3K, TGF-β3, Ki67 and Notch-1 in the 18 J/cm2 group were greater than those in the other groups in most samples. After chondrogenic induction, the expression of Col2A1, Sox9 and Aggrecan in the 18 J/cm2 group was significantly greater than that in the 4 J/cm2 and control groups in most of the samples. The variation in the MTT values and Src, PI3K, Akt, mTOR and GSK3β levels decreased with time. The results showed that 660-nm LED red light promoted proliferation and chondrogenic differentiation and affected the gene expression of MeSCs, and the effects on gene expression and mitochondrial activity decreased with time.

Abstract Tumor immune microenvironment (TIME) consists of intra-tumor immunological components and plays a significant role in tumor initiation, progression, metastasis, and response to therapy. Chimeric antigen receptor (CAR)-T cell immunotherapy has revolutionized the cancer treatment paradigm. Although CAR-T cell immunotherapy has emerged as a successful treatment for hematologic malignancies, it remains a conundrum for solid tumors. The heterogeneity of TIME is responsible for poor outcomes in CAR-T cell immunotherapy against solid tumors. The advancement of highly sophisticated technology enhances our exploration in TIME from a multi-omics perspective. In the era of machine learning, multi-omics studies could reveal the characteristics of TIME and its immune resistance mechanism. Therefore, the clinical efficacy of CAR-T cell immunotherapy in solid tumors could be further improved with strategies that target unfavorable conditions in TIME. Herein, this review seeks to investigate the factors influencing TIME formation and propose strategies for improving the effectiveness of CAR-T cell immunotherapy through a multi-omics perspective, with the ultimate goal of developing personalized therapeutic approaches.

Abstract Fungal diseases, such as powdery mildew and rusts, significantly affect the quality and yield of wheat. Pyramiding diverse types of resistance genes into cultivars represents the preferred strategy to combat these diseases. Moreover, achieving collaborative improvement between diseases resistance, abiotic stress, quality, and agronomic and yield traits is difficult in genetic breeding. In this study, the wheat cultivar, Guinong 29 (GN29), showed high resistance to powdery mildew and stripe rust at both seedling and adult plant stages, and was susceptible to leaf rust at the seedling stage but slow resistance at the adult-plant stage. Meanwhile, it has elite agronomic and yield traits, indicating promising coordination ability among multiple diseases resistance and other key breeding traits. To determine the genetic basis of these elite traits, GN29 was tested with 113 molecular markers for 98 genes associated with diseases resistance, stress tolerance, quality, and adaptability. The results indicated that two powdery mildew resistance (Pm) genes, Pm2 and Pm21, confirmed the outstanding resistance to powdery mildew through genetic analysis, marker detection, genomic in situ hybridization (GISH), non-denaturing fluorescence in situ hybridization (ND-FISH), and homology-based cloning; the stripe rust resistance (Yr) gene Yr26 and leaf rust resistance (Lr) genes Lr1 and Lr46 conferred the stripe rust and slow leaf rust resistance in GN29, respectively. Meanwhile, GN29 carries dwarfing genes Rht-B1b and Rht-D1a, vernalization genes vrn-A1, vrn-B1, vrn-D1, and vrn-B3, which were consistent with the phenotypic traits in dwarf characteristic and semi-winter property; carries genes Dreb1 and Ta-CRT for stress tolerance to drought, salinity, low temperature, and abscisic acid (ABA), suggesting that GN29 may also have elite stress-tolerance ability; and carries two low-molecular-weight glutenin subunit genes Glu-B3b and Glu-B3bef which contributed to high baking quality. This study not only elucidated the genetic basis of the elite traits in GN29 but also verified the capability for harmonious improvement in both multiple diseases resistance and other comprehensive traits, offering valuable information for breeding breakthrough-resistant cultivars.

The global health landscape has been persistently challenged by the emergence and re-emergence of infectious diseases. Traditional epidemiological models, rooted in the early 20th century, have provided foundational insights into disease dynamics. However, the intricate web of modern global interactions and the exponential growth of available data demand more advanced predictive tools. This is where AI for Science (AI4S) comes into play, offering a transformative approach by integrating artificial intelligence (AI) into infectious disease prediction. This paper elucidates the pivotal role of AI4S in enhancing and, in some instances, superseding traditional epidemiological methodologies. By harnessing AI's capabilities, AI4S facilitates real-time monitoring, sophisticated data integration, and predictive modeling with enhanced precision. The comparative analysis highlights the stark contrast between conventional models and the innovative strategies enabled by AI4S. In essence, AI4S represents a paradigm shift in infectious disease research. It addresses the limitations of traditional models and paves the way for a more proactive and informed response to future outbreaks. As we navigate the complexities of global health challenges, AI4S stands as a beacon, signifying the next phase of evolution in disease prediction, characterized by increased accuracy, adaptability, and efficiency.

Objectives We aimed to evaluate the association of interleukin-6 (IL-6) expression levels with stroke. Methods According to the set search strategy, we systematically screened relevant studies using PubMed and extracted study results regarding IL-6 from the literature for comprehensive quantitative analysis to explore the relationship between IL-6 level and stroke risk. Results This study included 15 publications with a total of 1696 participants, with 975 cases in the case group and 721 cases in the control group. Meta-analysis showed that IL-6 levels were significantly higher in the stroke population than those in the control group (standardized mean difference = 1.22, 95% confidence interval = 0.79–1.64). Subgroup analysis showed that there was no significant difference in heterogeneity for IL-6 detection methods between the two groups ( I 2 = 0, P = 0.47). The difference in heterogeneity test results regarding geographic region was statistically significant ( I 2 = 89.7%, P

Abstract Aim The relationship between vitamin D status and Kawasaki Disease (KD), as well as coronary artery lesion (CAL), has yet to be established. Methods A meta-analysis was conducted to assess the correlation between vitamin D status and KD, as well as the impact of vitamin D status on the progression of KD into CAL. Results The meta-analysis revealed a consistent and significant association between serum 25(OH)D level and the occurrence KD (studies N = 22; z = -3.51, P

Abstract Despite the high therapeutic response achieved with B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapy in relapsed and refractory multiple myeloma (R/R MM), primary resistance and relapse exist with single-target immunotherapy. Here, we design bispecific BC19 CAR T cells targeting BCMA/CD19 and evaluate antimyeloma activity in vitro and in vivo. Preclinical results indicate that BC19 CAR specifically recognize target antigens, and BC19 CAR T cells mediate selective killing of BCMA or CD19-positive cancer cells. BC19 CAR T cells also exhibit potent antigen-specific anti-tumor activity in xenograft mouse models. We conduct an open-label, single-arm, phase I/II study of BC19 CAR T cells in 50 patients with R/R MM (ChiCTR2000033567). The primary endpoint was safety. BC19 CAR T cells are well tolerated with grade 3 or higher cytokine release syndrome in 8% of patients and grade 1 neurotoxic events in 4% of patients, which meet the pre-specified primary endpoint. Secondary endpoints include overall response rate (92%), median progression-free survival (19.7 months), median overall survival (19.7 months) and median duration of response (not reached). Our study demonstrates that bispecific BC19 CAR T cells are feasible, safe and effective in treating patients with R/R MM.

Immune-mediated liver injury (ILI) is a condition where an aberrant immune response due to various triggers causes the destruction of hepatocytes. Fibroblast growth factor 4 (FGF4) was recently identified as a hepatoprotective cytokine; however, its role in ILI remains unclear. In patients with autoimmune hepatitis (type of ILI) and mouse models of concanavalin A (ConA)- or S-100-induced ILI, we observed a biphasic pattern in hepatic FGF4 expression, characterized by an initial increase followed by a return to basal levels. Hepatic FGF4 deficiency activated the mitochondria-associated intrinsic apoptotic pathway, aggravating hepatocellular apoptosis. This led to intrahepatic immune hyper-reactivity, inflammation accentuation, and subsequent liver injury in both ILI models. Conversely, administration of recombinant FGF4 reduced hepatocellular apoptosis and rectified immune imbalance, thereby mitigating liver damage. The beneficial effects of FGF4 were mediated by hepatocellular FGF receptor 4, which activated the Ca2+/calmodulin-dependent protein kinasekinase 2 (CaMKKβ) and its downstream phosphatase and tensin homologue-induced putative kinase 1 (PINK1)-dependent B-cell lymphoma 2-like protein 1-isoform L (Bcl-XL) signalling axis in the mitochondria. Hence, FGF4 serves as an early response factor and plays a protective role against ILI, suggesting a therapeutic potential of FGF4 and its analogue for treating clinical immune disorder-related liver injuries.

Improving mechanical properties of solder alloy can result in a decrease of its conductivity. The decrease in conductivity of the solder increases the generation of Joule heat and reduces the reliability of the joint. This problem can be solved by adjusting the solidification parameters of solders. In this paper, the effect of the growth rate (V) on the microstructure evolution, microhardness and electrical conductivity of directionally solidified (DS) Sn-0.7Cu-xCo (x = 0.5, 1.0, 1.5, 2.0, mass %) alloys was investigated. The Sn-0.7Cu-xCo alloys consists of a Sn-based solid solution (Sn-ss), Cu6Sn5 phase, and CoSn2 phase. The volume fraction of the CoSn2 phase increases with increasing Co content. In the DS specimen, the CoSn2 phases change from block-shaped to a long strip shape with a long axis direction close to the heat flow direction. With increasing V, the growth direction tends to become disordered due to the weakening of the heat flow effect. The microhardness of DS Sn-0.7Cu-xCo alloys increases with increasing V due to an increase of solution strengthening effect. The microhardness of DS Sn-0.7Cu-xCo alloys increases with increasing Co content under the same V. The conductivity of the DS Sn-0.7Cu-xCo alloys decreases with increasing V. The conductivity of the DS Sn-0.7Cu-xCo alloy is even better than that of the as-cast Sn-0.7Cu alloy when V ≤ 20 μm/s. The findings in the research provide a new way to improve the strength of solder without reducing its conductivity.

PurposeThe increasing emphasis on ecological responsibility within Chinese enterprises has underscored the critical role of employees’ green innovation behavior in enhancing environmental performance and enhancing core competitiveness. Grounded in the Ability, Motivation, and Opportunity (AMO) theoretical framework, this study employs configuration analysis to investigate the driving mechanisms behind the multi-factorial interplay affecting employees’ green innovation behaviors.MethodologyData was collected through questionnaires distributed among a random sample of 219 Chinese corporate employees. fuzzy-set Qualitative Comparative Analysis (fs-QCA) was then applied to identify the specific configurations contributing to high levels of green innovation behavior.Findings(1) There are three driving paths for employees’ green innovation behaviors: a leadership-organization co-driving path composed of green self-efficacy, environmentally transformative leadership, and organizational support; a leadership-driving path composed of green self-efficacy, environmentally transformative leadership, internal motivation, and external motivation; and an organization-driving path composed of green self-efficacy, organizational support, internal motivation, and external motivation. (2) There are three non-green innovation behavior-driven paths: they are divided into organizational support lack type, leadership-organizational joint lack type, and capability lack type. (3) Under specific conditions, motivational factors and environmental change leadership, motivational factors and sense of organizational support can promote employees’ green innovation through equivalent substitution.Originality(1) Significant emphasis is placed on examining how Ability, Motivation, and Opportunity synergize to shape employees’ green innovation behaviors, addressing a gap in the literature regarding their collective influence. (2) The study applies a configural approach to unravel the complex causal linkages influencing employees’ green innovation behaviors, offering detailed insights into the dynamics between individual attributes and contextual factors. (3) This research elucidates the combined effects of factors such as organizational support, leadership styles, and employees’ intrinsic and extrinsic motivations, and how they collaborate to foster an environment conducive to green innovation.ImplicationsThe findings not only enrich the theoretical understanding of green innovation behavior but also provide strategic recommendations for Chinese enterprises to encourage such behavior. These insights are essential for guiding sustainable development and enhancing competitive advantage.

Adjustments in flight initiation distance (FID) indicate how birds adapt to external environmental changes, including semi-natural ecosystems such as airports with regular disturbances. This study focused on sparrows (Passer montanus) as the research subject, because it is a dominant species with a high risk of bird strike events at airports. We investigated the FID and its influencing factors both inside and outside an airport compound to determine sparrows' vigilance and their adaptive adjustments to the airport environment. The FID of sparrows showed no significant variation between inside and outside the airport compound. However, a significant reduction of FID was exhibited during the breeding season. Group size showed a significant positive impact on the FID, somewhat supporting the many-eyes hypothesis, in which larger groups with more individuals may detect predators earlier. Additionally, the stimulus type and location influenced the effect of group size on FID, with most birds showing greater tolerance to vehicles than to humans, and being slightly bolder inside the airport than outside it. Overall, sparrows showed a higher tolerance to disturbance inside the airport compound and less vigilance to vehicles than to humans. Nevertheless, these adaptations may inadvertently form an ecological trap for bird populations around airports, exposing them to the dual threats of higher levels of raptor predation and the hazards of bird strikes. Thus multifaceted bird-scaring strategies and measures should be formulated to ensure flight safety and enhance avian survival during airport management.

Abstract Objectives To explore the relationship between cumulative ecological risk and individual risky behavior and multiple forms of aggregated behaviors among adolescents, and examine the gender differences. Methods A large-scale, nationally representative, and students-based investigation was conducted in rural and urban areas of eight provinces in China from October to December 2021. A total of 22 868 adolescents with an average age of 14.64 years completely standardized questionnaire in which the sociodemographic characteristics, socio-ecological risk factors and risky behaviors were used to analyze. Results Of included students, 48.4% encountered the high level of social-ecological risk. The prevalence of breakfast intake not daily, alcohol use (AU), smoking, physical inactivity, prolonged screen time (ST) on weekdays and weekends, suicidal ideation, suicidal plan, suicidal attempt, and non-suicidal self-injury (NSSI) was 41.0%, 11.9%, 3.4%, 61.9%, 15.1%, 51.1%, 27.7%, 13.9%, 6.5% and 27.0% respectively. 22.2% of participants engaged in high-risk behaviors. All were significantly influences of increased cumulative ecological risk on individual behavior and low-risk clustering behaviors separately. The odds ratio of breakfast intake not daily, AU, smoking, physical inactivity, prolonged ST in weekday and weekend, suicidal ideation, suicidal plan, suicidal attempt, and NSSI for the adjusted model in low versus high level of cumulative ecological risk was respectively significant in both boy and girls, and the ratio of odds ratios (ROR) was separately 0.95 (p = 0.228), 0.67 (p

Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases (CVDs), the world's primary cause of death. Ginkgo biloba, a well-known traditional Chinese medicine with notable cardiovascular actions, has been used as a cardio- and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries. Preclinical studies have shown that ginkgolide B, a bioactive component in Ginkgo biloba, can ameliorate atherosclerosis in cultured vascular cells and disease models. Of clinical relevance, several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases, such as ischemia stroke. Here, we present a comprehensive review of the pharmacological activities, pharmacokinetic characteristics, and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy. We highlight new molecular targets of ginkgolide B, including nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidase), lectin-like oxidized LDL receptor-1 (LOX-1), sirtuin 1 (SIRT1), platelet-activating factor (PAF), proprotein convertase subtilisin/kexin type 9 (PCSK9) and others. Finally, we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.

Highly integrated energy systems are on the rise due to increasing global demand. To capture the underlying physics of such interdisciplinary systems, we need a modern framework that unifies all forms of energy. Here, we apply modified Lagrangian mechanics to the description of multi-energy systems. Based on the minimum entropy production principle, we revisit fluid mechanics in the presence of both mechanical and thermal dissipations and propose using exergy flow as the unifying Lagrangian across different forms of energy. We illustrate our theoretical framework by modeling a one-dimensional system with coupled electricity and heat. We map the exergy loss rate in real space and obtain the total exergy changes. Under steady-state conditions, our theory agrees with the traditional formula but incorporates more physical considerations such as viscous dissipation. The integral form of our theory also allows us to go beyond steady-state calculations and visualize the local, time-dependent exergy flow density everywhere in the system. Expandable to a wide range of applications, our theoretical framework provides the basis for developing versatile models in integrated energy systems.

Abstract In predator–prey interactions, the prey faces extreme challenges from predation, which drives the evolution of defense or anti‐predator mechanisms. Compared with adult birds, nestlings are more vulnerable but not helpless. However, data on whether nestlings eavesdrop on the danger signals transmitted by other prey nestlings and the mechanisms of eavesdropping remain limited. In brood parasitism, common cuckoo (Cuculus canorus) nestlings, raised by host adults who are not closely related, offer an instructive system for studying the transmission and recognition of danger signals among nestlings of different species that share special relationships. We played back the distress calls of common cuckoo nestlings to nestlings of three sympatric host species (the oriental reed warbler Acrocephalus orientalis, which is a primary host of the common cuckoo, the reed parrotbill Paradoxornis heudei, an occasional host, and the vinous‐throated parrotbill Sinosuthora webbiana, which is not parasitized in the study area) to investigate whether the host nestlings reduced their begging behavior. We also quantified the degree of inhibition toward begging behavior for these nestlings. The results revealed that, in response to the distress calls, the three sympatric host species markedly suppressed their begging behavior. This response can likely be attributed to the innate response of host nestlings caused by the general characteristics of distress calls, rather than the acoustic similarity and phylogenetic relationship between host nestlings and cuckoo nestlings. Furthermore, we observed that upon hearing the distress calls of cuckoo nestlings, the oriental reed warbler nestlings exhibited the greatest reduction in the total number of calls compared to the other two host species, potentially owing to stronger predation and parasitic pressures. This study suggests that host nestlings can detect danger signals emitted by parasitic nestlings; however, further investigation is needed to determine whether they can respond to distress calls from unfamiliar nestlings in different regions.

Summary: Osteoporosis has gradually become a major public health problem. Further elucidation of the pathophysiological mechanisms that induce osteoporosis and identification of more effective therapeutic targets will have important clinical significance. Experiments in vitro on bone marrow stem cells (BMSCs) subjected to osteogenic and adipogenic differentiation and in vivo on surgical bilateral ovariectomy (OVX) mouse models revealed that exosomes of vascular endothelial cells (EC-EXOs) can promote osteogenic differentiation of BMSCs and inhibit BMSC adipogenic differentiation through miR-3p-975_4191. Both miR-3p-975_4191 and curcumin can target tumor necrosis factor (TNF) and act synergistically to regulate BMSCs fate differentiation and delay the progression of osteoporosis. Our findings suggest that EC-EXOs may exert a synergistic effect with curcumin in reversing the progression of osteoporosis by targeting TNF via miR-3p-975_4191. Our study may provide therapeutic options and potential therapeutic targets for osteoporosis and thus has important clinical implications.

Abstract Isoflavones are a group of phenolic compounds mostly restricted to plants of the legume family, where they mediate important interactions with plant-associated microbes, including in defense from pathogens and in nodulation. Their well-studied health promoting attributes have made them a prime target for metabolic engineering, both for bioproduction of isoflavones as high-value molecules, and in biofortification of food crops. A key gene in their biosynthesis, isoflavone synthase, was identified in legumes over two decades ago, but little is known about formation of isoflavones outside of this family. Here we identify a specialized wheat-specific isoflavone synthase, TaCYP71F53, which catalyzes a different reaction from the leguminous isoflavone synthases, thus revealing an alternative path to isoflavonoid biosynthesis and providing a non-transgenic route for engineering isoflavone production in wheat. TaCYP71F53 forms part of a biosynthetic gene cluster that produces a naringenin-derived O-methylated isoflavone, 5-hydroxy-2′,4′,7-trimethoxyisoflavone, triticein. Pathogen-induced production and in vitro antimicrobial activity of triticein suggest a defense-related role for this molecule in wheat. Genomic and metabolic analyses of wheat ancestral grasses further show that the triticein gene cluster was introduced into domesticated emmer wheat through natural hybridization ~9000 years ago, and encodes a pathogen-responsive metabolic pathway that is conserved in modern bread wheat varieties.

Recently, there has been a growing focus on researching ways to delay aging and protect against age-related illnesses. Small molecular exogenous peptides, sourced from dietary elements like animals, plants, and microorganisms, have demonstrated considerable potential in exerting anti-aging effects. Notably, natural food-derived peptides have exhibited enhanced stability, safety, absorption efficiency, and heightened biological activity. These attributes position them with a greater potential for mitigating aging-related disorders compared to alternative anti-aging drugs or phytochemicals. This review summarizes the origins, structural attributes, and isolation methods of natural food-derived peptides with anti-aging properties. It also explores how these external peptides improve aging-related conditions such as neurodegenerative diseases, skin aging, and metabolic disorders. The underlying mechanisms dictating their impact on well-conserved signaling pathways—encompassing oxidative stress, inflammation, apoptosis, and collagen synthesis—are meticulously elucidated. This paper engages in an insightful exploration of the key challenges and pivotal trajectories, grounded in ongoing research endeavors. As a result, this review is poised to offer authoritative scientific guidance and invaluable support for the practical implementation of natural food-derived peptides in the realm of anti-aging applications within the food, pharmaceutical, and cosmetic industries.

Abstract Objectives To determine whether smoking and drinking moderate the correlation between biological rhythm and mental health and the role of gender differences in these moderating effects. Methods Adolescents from three cities, all twelve middle schools (N = 7,986), named Shenzhen, Nanchang and Shenyang in China, were asked to complete a standardized questionnaire including the details of biological rhythm, psychological health, and the status of smoking and drinking. The PROCESS program was used to analyze whether smoking and drinking moderated the relationship between biological rhythm and psychological health. Results The analyses revealed poorer psychological health and greater likelihood of smoking and drinking in participants with higher scores for biological rhythm disorder (P

Alert and flight initiation distances are important elements of bird behavioral responses and indicators of their adaptation to external disturbances; therefore, they provide an important basis for bird conservation. With continual rapid advancements in drone technology, the use of drones in bird field surveys is becoming increasingly important. However, the disturbance impact of drones on birds remains controversial and needs further assessment. This study measured the distances at which coots (Fulica atra) tolerated drones in the Baiyangdian wetland, Northern China, over 42 days from August to November 2023 and at the end of July 2024. The results show the maximum alert distance (AD) and maximum flight initiation distance (FID) of the coot to be 44 m and 35 m, respectively. The coots showed no signs of disturbance when the drones flew at an altitude of 50 m. The AD of the coot showed a significant relationship with whether it saw the drones in advance, environmental conditions, and the drone’s behavior before it approached, whereas the FID was only significantly affected by whether the coot saw the drones in advance. The sight of drones in advance considerably increased the AD and FID.

Astragalus membranaceus saponins are the main components of A. membranaceus, a plant widely used in traditional Chinese medicine. Recently, research on the anti-cancer effects of A. membranaceus saponins has received increasing attention. Numerous in vitro and in vivo experimental data indicate that A. membranaceus saponins exhibit significant anti-cancer effects through multiple mechanisms, especially in inhibiting tumor cell proliferation, migration, invasion, and induction of apoptosis, etc. This review compiles relevant studies on the anti-cancer properties of A. membranaceus saponins from various databases over the past two decades. It introduces the mechanism of action of astragalosides, highlighting their therapeutic benefits in the management of cancer. Finally, the urgent problems in the research process are highlighted to promote A. membranaceus saponins as an effective drug against cancer.

The unicellular green alga Chlamydomonas reinhardtii (hereafter Chlamydomonas) possesses both plant and animal attributes, and it is an ideal model organism for studying fundamental processes such as photosynthesis, sexual reproduction, and life cycle. N6-methyladenosine (m6A) is the most prevalent mRNA modification, and it plays important roles during sexual reproduction in animals and plants. However, the pattern and function of m6A modification during the sexual reproduction of Chlamydomonas remain unknown. Here, we performed transcriptome and methylated RNA immunoprecipitation sequencing (MeRIP-seq) analyses on six samples from different stages during sexual reproduction of the Chlamydomonas life cycle. The results show that m6A modification frequently occurs at the main motif of DRAC (D = G/A/U, R = A/G) in Chlamydomonas mRNAs. Moreover, m6A peaks in Chlamydomonas mRNAs are mainly enriched in the 3′ untranslated regions (3′UTRs) and negatively correlated with the abundance of transcripts at each stage. In particular, there is a significant negative correlation between the expression levels and the m6A levels of genes involved in the microtubule-associated pathway, indicating that m6A modification influences the sexual reproduction and the life cycle of Chlamydomonas by regulating microtubule-based movement. In summary, our findings are the first to demonstrate the distribution and the functions of m6A modification in Chlamydomonas mRNAs and provide new evolutionary insights into m6A modification in the process of sexual reproduction in other plant organisms.

Abstract To improve the blockchain consensus algorithm practical Byzantine fault tolerance (PBFT) with random master node selection, which has high communication overhead and a small supported network size, this paper proposes a Byzantine fault tolerant consensus algorithm based on credit (CBFT) enhanced with a grouping and credit model. The CBFT algorithm divides the network nodes according to the speed of their response to the management nodes, resulting in different consensus sets, and achieves consensus within and outside the group separately to reduce communication overhead and increase system security. Second, the nodes are divided into different types according to the credit model, each with different responsibilities to reduce the probability that the master node is a malicious node. Experimental results show that the throughput of the CBFT algorithm is 3.1 times that of PBFT and 1.5 times that of GPBFT when the number of nodes is 52. Our scheme has latency that is 7.4% that of PBFT and 38.8% that of GPBFT; CBFT has communication overhead that is 6.4% that of PBFT and 87.3% that of GPBFT. The number of nodes is 300, and the Byzantine fault tolerance is improved by 59.3%. These improvements are clearer with the increase in the number of nodes.

Powdery mildew is one of the most severe diseases affecting wheat yield and quality and is caused by Blumeria graminis f. sp. tritici (Bgt). Host resistance is the preferred strategy to prevent this disease. However, the narrow genetic basis of common wheat has increased the demand for diversified germplasm resources against powdery mildew. Wheat relatives, especially the secondary gene pool of common wheat, are important gene donors in the genetic improvement of common wheat because of its abundant genetic variation and close kinship with wheat. In this study, a series of 137 wheat relatives, including 53 Triticum monococcum L. (2n = 2x = 14, AA), 6 T. urartu Thumanjan ex Gandilyan (2n = 2x = 14, AA), 9 T. timopheevii Zhuk. (2n = 4x = 28, AAGG), 66 T. aestivum subsp. spelta (2n = 6x = 42, AABBDD), and 3 Aegilops speltoides (2n = 2x = 14, SS) were systematically evaluated for their powdery mildew resistance and composition of Pm genes. Out of 137 (60.58%) accessions, 83 were resistant to Bgt isolate E09 at the seedling stage, and 116 of 137 (84.67%) wheat relatives were resistant to the mixture of Bgt isolates at the adult stage. This indicates that these accessions show a high level of resistance to powdery mildew. Some 31 markers for 23 known Pm genes were used to test these 137 accessions, and, in the results, only Pm2, Pm4, Pm6, Pm58, and Pm68 were detected. Among them, three Pm4 alleles (Pm4a, Pm4b, and Pm4f) were identified in 4 T. subsp. spelta accessions. q-RT PCR further confirmed that Pm4 alleles played a role in disease resistance in these four accessions. The phylogenetic tree showed that the kinship of Pm4 was close to Pm24 and Sr62. This study not only provides reference information and valuable germplasm resources for breeding new wheat varieties with disease resistance but also lays a foundation for enriching the genetic basis of wheat resistance to powdery mildew.

Background Since most infants are usually discharged before age 48–72 hours, peak bilirubin levels will almost always occur after discharge. Parents may be the first to observe the onset of jaundice after discharge, but visual assessment is unreliable. The jaundice colour card (JCard) is a low-cost icterometer designed for the assessment of neonatal jaundice. The objective of this study was to evaluate parental use of JCard to detect jaundice in neonates.Methods We conducted a multicentre, prospective, observational cohort study in nine sites across China. A total of 1161 newborns ≥35 weeks of gestation were enrolled in the study. Measurements of total serum bilirubin (TSB) levels were based on clinical indications. The JCard measurements by parents and paediatricians were compared with the TSB.Results JCard values of parents and paediatricians were correlated with TSB (r=0.754 and 0.788, respectively). The parents’ and paediatricians’ JCard values 9 had sensitivities of 95.2% vs 97.6% and specificities of 84.5% vs 71.7% for identifying neonates with TSB ≥153.9 µmol/L. The parents’ and paediatricians’ JCard values 15 had sensitivities of 79.9% vs 89.0% and specificities of 66.7% vs 64.9% for identifying neonates with TSB ≥256.5 µmol/L. Areas under the receiver operating characteristic curves of parents for identifying TSB ≥119.7, ≥153.9, ≥205.2, and ≥256.5 µmol/L were 0.967, 0.960, 0.915, and 0.813, respectively, and those of paediatricians were 0.966, 0.961, 0.926 and 0.840, respectively. The intraclass correlation coefficient was 0.933 between parents and paediatricians.Conclusion The JCard can be used to classify different levels of bilirubin, but it is less accurate with high bilirubin levels. The JCard diagnostic performance of parents was slightly lower than that of paediatricians.

IntroductionThe plant microbiome is the second genome of plants and is important for plant growth and health. Dendrobium is an epiphytic herbal plant of the family Orchidaceae that is often found attached to tree trunks or rocks and exhibits different cultivation modes. Microbiological and metabolite studies of Dendrobium denneanum Kerr (D. denneanum) in different cultivation modes can reveal important relationships between Dendrobium spp., their microbiomes, and their pharmacological substances, which is important for sustainable agricultural development and human health, particularly in the study of medicinal plants.MethodsIn this study, three cultivation modes, living tree epiphytic (LT), stone epiphytic (SE), and pot cultivation (PO) of D. denneanum in the same environment were selected, and the metabolites were using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Subsequently, differential metabolites were screened, the rhizosphere and root endosphere microorganisms were sequenced via high-throughput sequencing, and the 16S rRNA gene/ITS sequences were obtained.ResultsThe main microbial taxa in the rhizosphere and root endosphere of D. denneanum included bacteria belonging to Proteobacteria, Actinobacteria, and Actinobacteria, and the fungi Basidiomycota and Ascomycota, whose abundances varied in different cultivation modes. Soil properties affect the composition of D. denneanum metabolites and root microbiome, among which, soil total phosphorus (TP) and pH in particular are important factors for soil microorganisms. Studies of root microbial communities have shown that root endosphere fungi are similar to rhizosphere fungi with microbial enrichment occurring from the external environment to the internal structures. Root microbial communities and metabolites correlation analyses revealed significant correlations between rhizosphere microbes, as well as endophytes and metabolites. For example, the rhizosphere bacterium genus Occallatibacter and root endosphere fungus Clonostachys showed a significant negative correlation with the pharmacodynamic substance gigantol in D. denneanum (P

Abstract Background Degenerative lumbar scoliosis (DLS) is a common degenerative disease of the spine, that predominates in the elderly, and causes spinal deformities along with severe pain and reduced quality of life. The relationship between DLS and degenerated discs is now a new direction of research. Our study aimed to the relationship between the imaging parameters of coronal imbalance and the number of degenerated discs in patients with degenerative lumbar scoliosis and analyzed the segmental distribution of the degenerated discs in patients with DLS. Methods We performed a retrospective analysis of the imaging of 40 patients who met the inclusion criteria who attended our outpatient clinic between April 2021 and July 2021, measuring the intervertebral space height of the AV (high side and low side), Cobb angle, and AVT (Apical vertebral translation) from coronal X-ray. Degenerated discs were evaluated by the Pfirrmann score based on T2-weighted magnetic resonance images. We record the number of degenerated discs (Graded as Grade III, Grade IV or Grade V by the Pfirrmann score) and the segments in which they are located. Finally, we explore the relationship between the imaging parameters of coronal imbalance and the number of degenerated discs in patients with DLS. Result Among the 40 patients with DLS in our study, all patients had degenerated discs in the lumbar spine, 95% of patients had degenerated discs(Pfirrmann score Grade III, Grade IV or Grade V) in 2 or more segments, with the L4-L5 segment being the most involved segment with the most degenerated discs, followed by the L3-L4 segment and the L5-S1 segment. There was no statistically significant relationship between the number of degenerated discs and the coronal imbalance in patients with DLS. Conclusion Our results showed an association between DLS and degenerated discs, but there was no statistically significant relationship between imbalance in the coronal plane of the lumbar spine and the number of degenerated discs in patients with DLS. The distribution of degenerated disc segments in patients with DLS showed a higher likelihood of disc degeneration in 2 or more segments, and a higher frequency of disc degeneration in the inferior disc and in the adjacent segments of the AV.

Accurately predicting the thermal characteristics and heat transfer distribution of the rotating detonation engine (RDE) and acquiring a clear understanding of the performance and mechanism of the rotating detonation are of great significance for achieving the safe and reliable long-duration operation of RDEs. Using RP-3 as fuel, a long-duration experimental study is performed on a 220 mm-diameter RDC to investigate the details with respect to the thermal environment. The heat flux at the typical location and the average heat flux of both the inner and outer cylinders are measured, respectively. Meanwhile, the peak pressure of the rotating detonation wave (RDW) and specific thrust are analyzed. When the ER is between 0.5 and 1 (oxidizer 2 kg/s), the stable rotating detonation mode is obtained, and the detonation duration is set as 40 s to accurately calculate the heat released by the detonation combustion. The heat flux in the upstream region of the RDW location ranges from 2.40 × 105 W/m2 to 3.17 × 105 W/m2, and the heat flux in the downstream area of the RDW location ranges from 1.05 × 106 W/m2 to 1.28 × 106 W/m2. The results demonstrate the important role of the detonation combustion zone, and the thrust performance of RDC can be improved by making the RDW move forward along the RDC axis, which is the optimal direction of detonation combustion. Through a comparison of average heat flux under different conditions, it is found that the heat released by the RDC is directly related to its thrust. In addition, the average heat flux of the inner cylinder is about three times that of the outer cylinder for the two-phase RDC with a Tesla valve intake structure, indicating that the high-temperature combustion product is closer to the inner wall. Therefore, more thermal protection should be allocated to the inner cylinder, and a more systematic analysis of the two-phase flow field distribution in the annular combustion chamber should be carried out to improve the thrust performance. In this paper, the average heat flux of the inner and outer cylinders of the RDC as well as the typical local heat flux of the outer cylinders is quantitatively measured by means of experiments, which not only deepens the understanding of RDC flow field distribution, but also provides quantitative boundary conditions for the thermal protection design of RDCs.

Abstract Purpose Adolescents exposed to adverse childhood experiences (ACEs) are at increased risk for health-compromising behaviors. However, few studies have investigated how ACEs correlate with patterns of health risk behaviors (HRBs) during adolescence, a crucial developmental period. The aim was to extend the current knowledge about the relationship between ACEs and HRB patterns among adolescents, and to explore gender differences. Methods A multi-centered population-based survey was conducted in 24 middle schools in three provinces across China between 2020 and 2021. A total of 16,853 adolescents effectively completed anonymous questionnaires covering exposure to eight ACE categories and 11 HRBs. Clusters were identified using latent class analysis. Logistic regression models were utilized to test the association between them. Results There were four classes of HRB patterns: “Low all” (58.35%), “Unhealthy lifestyle” (18.23%), “Self-harm” (18.42%), and “High all” (5.0%). There were significant differences between HRB patterns in terms of the different numbers and types of ACEs in three logistic regression models. Specifically, compared to “Low all,” different types of ACEs were positively associated with the three other HRB patterns, and there were significant trends toward increase in the three latent classes of HRBs with higher ACEs. In general, females with ACEs had a higher risk of “High all” except sexual abuse than males. Conclusion Our study comprehensively considers the association between ACEs and aggregation categories of HRBs. The results support efforts to improve clinical healthcare, and future work may explore protective factors based on individual, family, and peer education to mitigate the negative trajectory of ACEs.

The patterns of interaction between terrestrial vegetation and the atmosphere are complex, and some are poorly understood. Linear or general linear methods have been widely used to explore the dynamics of vegetation and climate changes. However, linear thinking may hinder our understanding of complex nonlinear systems, and it is difficult to extract the underlying causality of linear correlations directly from observational data. In this study, we aimed to quantify the interactions between vegetation and climate, using nonlinear dynamical methods based on state-space reconstruction and datasets from Chinese meteorological stations and remote sensing data during 1982–2015 in Northeast China (NEC). Specifically, we identified the causal links between meteorological factors (temperature and precipitation) and the vegetation index (NDVI) by reconstructing the state space from historical records. During the study period, vegetation exhibited a strong bidirectional causal relationship with both temperature and precipitation across Northeast China. The NDVI can be accurately reconstructed from the state information of meteorological factors (temperature and precipitation). The results of the multivariate EDM scenarios reveal varying sensitivities of different vegetation types to meteorological factors. Overall, slight temperature changes have a stronger impact on vegetation compared to precipitation. Mixed forest and broad-leaved forest demonstrate lower sensitivity to precipitation changes compared to other vegetation types. This study on the causal relationship between vegetation and meteorological factors in Northeast China contributes to a deeper understanding of climate change and vegetation feedback in middle and high latitudes. Our work demonstrates that the EDM-based convergent cross-mapping nonlinear causal analysis method is valuable for comprehending the interactions within complex systems in earth science.

The predictive business process monitoring mainly focuses on the performance prediction of business process execution, i.e., predicting the next activity, the execution time of the next activity, and the remaining time, respectively, for an ongoing process instance based on the knowledge gained from historical event logs. Although there is a specific relationship between these three tasks, recent research has focused on training separate prediction models for each task, resulting in high costs and time complexity. Additionally, existing technologies are limited in their ability to capture long-distance dependent features in process instances, further impeding prediction performance. To address these issues, this paper proposes the MTLFormer approach, which leverages the self-attention mechanism of the Transformer network and conducts multi-task parallel training through shared feature representation obtained from different tasks. Our approach reduces the time complexity of model training while simultaneously improving prediction performance. We extensively evaluate our approach on four real-life event logs, demonstrating its capability to achieve multi-task online real-time prediction and effectively improve prediction performance.

Abstract Background Hyaluronic acid (HA) promotes cancer metastasis; however, the currently approved treatments do not target HA. Metastatic renal carcinoma (mRCC) is an incurable disease. Sorafenib (SF) is a modestly effective antiangiogenic drug for mRCC. Although only endothelial cells express known SF targets, SF is cytotoxic to RCC cells at concentrations higher than the pharmacological-dose (5-µM). Using patient cohorts, mRCC models, and SF combination with 4-methylumbelliferone (MU), we discovered an SF target in RCC cells and targeted it for treatment. Methods We analyzed HA-synthase (HAS1, HAS2, HAS3) expression in RCC cells and clinical (n = 129), TCGA-KIRC (n = 542), and TCGA-KIRP (n = 291) cohorts. We evaluated the efficacy of SF and SF plus MU combination in RCC cells, HAS3-transfectants, endothelial-RCC co-cultures, and xenografts. Results RCC cells showed increased HAS3 expression. In the clinical and TCGA-KIRC/TCGA-KIRP cohorts, higher HAS3 levels predicted metastasis and shorter survival. At > 10-µM dose, SF inhibited HAS3/HA-synthesis and RCC cell growth. However, at ≤ 5-µM dose SF in combination with MU inhibited HAS3/HA synthesis, growth of RCC cells and endothelial-RCC co-cultures, and induced apoptosis. The combination inhibited motility/invasion and an HA-signaling-related invasive-signature. We previously showed that MU inhibits SF inactivation in RCC cells. While HAS3-knockdown transfectants were sensitive to SF, ectopic-HAS3-expression induced resistance to the combination. In RCC models, the combination inhibited tumor growth and metastasis with little toxicity; however, ectopic-HAS3-expressing tumors were resistant. Conclusion HAS3 is the first known target of SF in RCC cells. In combination with MU (human equivalent-dose, 0.6–1.1-g/day), SF targets HAS3 and effectively abrogates mRCC.

Natural products, and especially the active ingredients found in traditional Chinese medicine (TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such, traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and single-cell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.

Abstract Astrocytes are important components of the innate immune response in the central nervous system (CNS), involving in the inflammatory and neurotoxic responses that occur in CNS diseases, such as multiple sclerosis (MS). Recent studies have shown that SARM1 plays a critical role in axonal degeneration and inflammation. However, the detailed role of astrocytic SARM1 in MS remains unclear. Here, we established the MS model of mice - experimental autoimmune encephalomyelitis (EAE) and found that SARM1 was upregulated in astrocytes of the spinal cords of EAE mice. Moreover, conditional knockout of astrocytic SARM1 (SARM1 GFAP -CKO mice, SARM1 Aldh1L1 -CKO mice) delayed EAE with later onset, alleviated the inflammatory infiltration, and inhibited the demyelination and neuronal death. Mechanically, RNA-seq revealed that the expression of glial-derived neurotrophic factor (GDNF) was upregulated in SARM1 −/− astrocytes. Western blot and immunostaining further confirmed the upregulation of GDNF in spinal cord astrocytes of SARM1 GFAP -CKO EAE mice. Interestingly, the downregulation of GDNF by streptozotocin (STZ, a drug used to downregulate GDNF) treatment worsened the deficits of SARM1 GFAP -CKO EAE mice. These findings identify that astrocytic SARM1 promotes neuroinflammation and axonal demyelination in EAE by inhibiting the expression of GDNF, reveal the novel role of SARM1/GDNF signaling in EAE, and provide new therapeutic ideas for the treatment of MS.

Prostatitis, a prevalent urinary tract disorder in males, has a complex etiology that leads to severe clinical discomfort. Pule’an Tablets, a classic single-component formulation primarily based on rapeseed pollen, have been clinically proven to have a beneficial therapeutic effect on both prostatitis and benign prostatic hyperplasia. However, there is currently a lack of research on the chemical composition and mechanisms of action of Pule’an Tablets in treating prostatitis. In this study, using liquid chromatography–mass spectrometry (LC-MS), a total of 53 compounds in Pule’an Tablets were identified, including flavonoids, phenylpropionamides, lipids, glucosinolates, and nucleic acids. Subsequently, through a network pharmacology analysis, potential target genes and their mechanisms of action were predicted accordingly. The results suggested that genes such as LPAR5, LPAR6, LPAR4, LPAR3, LPAR2, LPAR1, F2, ENPP2, MMP9, and TNF, along with pathways like prostate cancer, endocrine resistance, bladder cancer, and the IL-17 signaling pathway, may represent potential pathways involved in the therapeutic effects of Pule’an Tablets. This study represents the first systematic investigation into the chemical composition of Pule’an Tablets, shedding light on the potential mechanisms underlying their efficacy in treating prostatitis. These findings could serve as a valuable reference for future pharmacological research on Pule’an Tablets.

BackgroundThe current oil production determines oil workers’ occupational noise exposure. Without effective protection, noise will affect various aspects of worker’s body functions, including acting on the adrenal cortex system and resulting in renal function damage. ObjectiveTo evaluate the associations of noise exposure and its cumulative exposure level with renal function impairment of oil workers. MethodsOil workers from a collective medical examination in a hospital were selected as the study subjects. In accordance with the national standard Measurement of Physical Agents in the Workplace Part 8: Noise (GBZ/T 189.8—2007), noise exposure was measured three times at the oil workers' work site, and their average value was calculated to obtain the cumulative noise exposure (CNE). A questionnaire survey was conducted to collect general information such as socio-demographic characteristics, family history, lifestyles, and occupational history. All blood biochemical indicators were measured in the fasting state. Renal function impairment was judged based on the glomerular filtration rate. The relationship between CNE and renal function was analyzed using receiver operating characteristic curve (ROC) for workers with noise exposure. ResultsA total of 2 917 subjects were included in the study and their prevalence of renal function impairment was 14.2%. The univariate analysis results suggested statistically significant differences in the prevalence of renal function impairment among the oil workers grouped by having hypertension or not, gender, age, marital status, marital status, smoking, and alcohol consumption (P＜0.05); the prevalence of renal impairment was significantly higher in those with abnormal values of uric acid, total cholesterol, triglycerides, high-density lipoprotein, and fasting glucose than in those with normal values (P＜0.05); the oil workers with noise exposure [n=1565, 53.7%, equivalent sound level ≥80 dB(A)] showed a higher prevalence of renal function impairment than those without (P＜0.05). The results of multiple logistic regression analysis showed that being female (OR=2.811, 95%CI: 1.960-4.030), age at 31 years and above (OR31-40=3.502, 95%CI: 1.402-8.751; OR41-50=4.255, 95%CI: 1.759-10.291; OR≥51=7.179, 95%CI: 2.864-17.996), showing abnormal uric acid (OR=5.932, 95%CI: 4.486-7.843), having hypertension (OR=1.593, 95%CI: 1.230-2.063), alcohol consumption (OR=2.648, 95%CI: 1.346-5.212), and smoking (OR=1.816, 95%CI: 1.133-2.911) had higher risks of developing renal function impairment; besides, those exposed to noise had 1.351 times (95%CI: 1.073-1.702) higher risks of developing renal function impairment than non-exposed individuals. Noise-exposed oil workers in the renal impairment group had higher noise exposure intensity and CNE compared to the noise-exposed oil workers in the normal renal function group (P＜0.05), and the workers had an increased risk of renal function impairment when the CNE was >95.85 dB(A)·year versus CNE ≤ 95.85 dB(A)·year (OR=2.583, 95%CI: 1.956-3.411). ConclusionExposure to noise, higher noise exposure intensity, and higher level of CNE may be associated with developing renal function impairment in oil workers. Oil workers with CNE above 95.85 dB(A)·year are at an increased risk of renal impairment.

Abstract Sensing sensitivity is the key performance of optical tweezers. By adjusting the frequency and magnitude of an applied Coulomb force as an input of optical tweezers, we directly measured the sensitivity and signal-to-noise ratio (SNR) of a system and indirectly calculated the actual noise magnitude. Combined with an output filter, the relationship between the SNR and bandwidths was studied. We established the simulation model of a system using Simulink and simulated the relationship between the SNR and magnitude of the input forces and filter bandwidths. In addition, we built an experimental system to determine the relationship between the SNR and the magnitude of the input forces and filter bandwidths. The actual minimum detectable force was measured as 1.8275×10−17 N at a 1 Hz bandwidth. The experimental results were correlated with the simulation and theoretical results, confirming the effectiveness of the proposed method and demonstrating the high sensitivity of vacuum optical tweezers as mechanical sensors. We proposed a novel method of calibration and measurement of system sensing parameters by applying an actual force that was more direct and precise than the theoretical calculation method that requires accurate fitting parameters, such as the particle radius and density. This method can be employed to analyze the system noise and phase characteristics to confirm and improve the real performance of the system.

Numerous studies have proposed search engine-based estimation of COVID-19 prevalence during the COVID-19 pandemic; however, their estimation models do not consider the impact of various urban socioeconomic indicators (USIs). This study quantitatively analysed the impact of various USIs on search engine-based estimation of COVID-19 prevalence using 15 USIs (including total population, gross regional product (GRP), and population density) from 369 cities in China. The results suggested that 13 USIs affected either the correlation (SC-corr) or time lag (SC-lag) between search engine query volume and new COVID-19 cases (p

Autism spectrum disorder (ASD) is associated with severe impairment in social functioning. Visual information processing provides nonverbal cues that support social interactions. ASD children exhibit abnormalities in visual orientation, continuous visual exploration, and visual–spatial perception, causing social dysfunction, and mechanisms underlying these abnormalities remain unclear. Transmission of visual information depends on the retina-lateral geniculate nucleus–visual cortex pathway. In ASD, developmental abnormalities occur in rapid expansion of the visual cortex surface area with constant thickness during early life, causing abnormal transmission of the peak of the visual evoked potential (P100). We hypothesized that abnormal visual perception in ASD are related to the abnormal visual information transmission and abnormal development of visual cortex in early life, what’s more, explored the mechanisms of abnormal visual symptoms to provide suggestions for future research.

Pheromone cues released from hosts or prey are of crucial importance to natural enemies for prey and habitat location. The use of herbivorous insect sex pheromones has long been considered as a potential pest control alternative that is non-toxic and harmless to beneficials. We hypothesized that Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae), a major predatory coccinellid beetle of the devastating migratory pest Spodoptera frugiperda (Smith) (Lepidoptera: Noctuidae), could perceive and use the sex pheromone of S. frugiperda to locate its habitat. Here we tested the electrophysiological and behavioral responses of H. axyridis to the two components Z7-12:Ac and Z9-14:Ac of S. frugiperda sex pheromone by using electroantennography (EAG) and Y-tube bioassay. The 3D modeling of H. axyridis odorant-binding proteins (HaxyOBPs) and molecular docking were also performed. The results showed that both female and male H. axyridis exhibited significantly higher electrophysiological and behavioral responses to Z9-14:Ac at the concentrations of 0.001, 0.01, and 0.1 μg/μL, while no significant electrophysiological and behavioral responses of H. axyridis were observed to Z7-12:Ac. The blend of Z7-12:Ac and Z9-14:Ac at the ratio of 1:100 had a significant attraction to both male and female H. axyridis at the concentrations of 0.01 and 0.1 μg/μL based on electrophysiological and behavioral assays, but no significant behavioral responses were observed at the ratios of 1:9. According to the 3D modeling of HaxyOBPs and molecular docking, HaxyOBP12 has a good affinity with Z9-14:Ac. Z9-14:Ac is bound to the HaxyOBP12 by hydrogen bonding and hydrophobic interactions. However, there were no credible docking results between HaxyOBPs and Z7-12:Ac. Our findings revealed that H. axyridis can perceive Z9-14:Ac and could use it as a chemical cue to locate prey habitat. We speculated that Z7-12:Ac, which showed some antagonistic effect toward the response of H. axyridis to Z9-14:Ac, could improve the adaptability of S. frugiperda in the presence of predators. This study provides new insights into the application of pheromones to manipulate natural enemy behavior for pest control.

Objectives: The aim of the study was to reconstruct the complete transmission chain of the COVID-19 outbreak in Beijing's Xinfadi Market using data from epidemiological investigations, which contributes to reflecting transmission dynamics and transmission risk factors. Methods: We set up a transmission model, and the model parameters are estimated from the survey data via Markov chain Monte Carlo sampling. Bayesian data augmentation approaches are used to account for uncertainty in the source of infection, unobserved onset, and infection dates. Results: The rate of transmission of COVID-19 within households is 9.2%. Older people are more susceptible to infection. The accuracy of our reconstructed transmission chain was 67.26%. In the gathering place of this outbreak, the Beef and Mutton Trading Hall of Xinfadi market, most of the transmission occurs within 20 m, only 19.61% of the transmission occurs over a wider area (>20 m), with an overall average transmission distance of 13.00 m. The deepest transmission generation is 9. In this outbreak, there were 2 abnormally high transmission events. Conclusions: The statistical method of reconstruction of transmission trees from incomplete epidemic data provides a valuable tool to help understand the complex transmission factors and provides a practical guideline for investigating the characteristics of the development of epidemics and the formulation of control measures.

Abstract Although various strategies have been included in nanotoxicity evaluation, epitranscriptomics has rarely been integrated into this field. In this proof-of-concept study, N6-methyladenosine (m6A) changes of mRNA in HEK293T cells induced by three bovine serum albumin (BSA)-templated Au, CuS and Gd2O3 nanoparticles are systematically explored, and their possible biological mechanisms are preliminarily investigated. It has been found that all the three BSA-templated nanoparticles can reduce m6A levels, and the genes with reduced m6A are enriched for TGF-beta signaling, which is critical for cell proliferation, differentiation and apoptosis. Further results indicate that abnormal aggregation of m6A-related enzymes at least partly account for the nanoparticle-induced epitranscriptomic changes. These findings demonstrate that epitranscriptomics analysis can provide an unprecedented landscape of the biological effect induced by nanomaterials, which should be involved in the nanotoxicity evaluation to promote the potential clinical translation of nanomaterials.

The SARS-CoV-2 virus, also known as the severe acute respiratory syndrome coronavirus 2, has raised great threats to humans. The connection between the SARS-CoV-2 virus and cancer is currently unclear. In this study, we thus evaluated the multi-omics data from the Cancer Genome Atlas (TCGA) database utilizing genomic and transcriptomic techniques to fully identify the SARS-CoV-2 target genes (STGs) in tumor samples from 33 types of cancers. The expression of STGs was substantially linked with the immune infiltration and may be used to predict survival in cancer patients. STGs were also substantially associated with immunological infiltration, immune cells, and associated immune pathways. At the molecular level, the genomic changes of STGs were frequently related with carcinogenesis and patient survival. In addition, pathway analysis revealed that STGs were involved in the control of signaling pathways associated with cancer. The prognostic features and nomogram of clinical factors of STGs in cancers have been developed. Lastly, by mining the cancer drug sensitivity genomics database, a list of potential STG-targeting medicines was compiled. Collectively, this work demonstrated comprehensively the genomic alterations and clinical characteristics of STGs, which may offer new clues to explore the mechanisms on a molecular level between SARS-CoV-2 virus and cancers as well as provide new clinical guidance for cancer patients who are threatened by the COVID-19 epidemic.

Abstract Cholesterols are the main components of myelin, and are mainly synthesized in astrocytes and transported to oligodendrocytes and neurons in the adult brain. It has been reported that Hippo/yes-associated protein (YAP) pathways are involved in cholesterol synthesis in the liver, however, it remains unknown whether YAP signaling can prevent the demyelination through promoting cholesterol synthesis in experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of multiple sclerosis characterized by neuroinflammation and demyelination. Here, we found that YAP was upregulated and activated in astrocytes of spinal cords of EAE mice through suppression of the Hippo pathway. YAP deletion in astrocytes aggravated EAE with earlier onset, severer inflammatory infiltration, demyelination, and more loss of neurons. Furthermore, we found that the neuroinflammation was aggravated and the proliferation of astrocytes was decreased in YAPGFAP-CKO EAE mice. Mechanically, RNA-seq revealed that the expression of cholesterol-synthesis pathway genes such as HMGCS1 were decreased in YAP−/− astrocytes. qPCR, western blot, and immunostaining further confirmed the more significant reduction of HMGCS1 in spinal cord astrocytes of YAPGFAP-CKO EAE mice. Interestingly, upregulation of cholesterol-synthesis pathways by diarylpropionitrile (DPN) (an ERβ-ligand, to upregulate the expression of HMGCS1) treatment partially rescued the demyelination deficits in YAPGFAP-CKO EAE mice. Finally, activation of YAP by XMU-MP-1 treatment promoted the expression of HMGCS1 in astrocytes and partially rescued the demyelination and inflammatory infiltration deficits in EAE mice. These findings identify unrecognized functions of astrocytic YAP in the prevention of demyelination through promoting cholesterol synthesis in EAE, and reveal a novel pathway of YAP/HMGCS1 for cholesterol synthesis in EAE pathology.