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The integration of TiCN particles into superalloy composites for laser powder bed fusion (LPBF) and the construction of Triply Periodic Minimal Surface (TPMS) lattice structures have been understudied. This research systematically examines the microstructure and mechanical properties of LPBF-processed 10 vol% micron sized TiCN particle reinforced Inconel 718 (IN718) composites. The compressive behavior of the resultant TPMS lattice structures, derived from the TiCN-IN718 composite, was scrutinized through a combination of experimental testing and Finite Element (FE) simulation. The micro-sized TiCN reinforcement is demonstrated to notably augment the hardness, tensile strength, and wear resistance of the LPBFed TiCN-IN718 composite. Furthermore, the application of homogenization-solution-aging (HSA) heat treatment is shown to provide additional enhancements to the composite's mechanical behavior. Both the TiCN reinforcement and the HSA heat treatment are identified as pivotal factors influencing the compressive response of the TPMS lattice structures. Experimental findings indicate that the HSA-treated D-structure attains the highest compressive strength, reaching 122 MPa, outperforming both the G- and P-structures. During quasi-static compression testing, the D- and G-structures undergo a layer-by-layer collapse, while the P-structure exhibits tilt shear band behavior. The congruence between FE simulation results and experimental data substantiates the simulation's reliability and its capacity to accurately evaluate the mechanical behavior of TPMS lattice structures.

The hybrids (BY) derived from blunt snout bream (Megalobrama amblycephala, BSB, ♀) and Bleeker's yellow tai (Xenocypris davidi Bleeker, YT, ♂) have a fast growth rate and body thickness. However, the molecular mechanisms underlying the growth advantage of BY are still unclear. MSTN, a member of the TGF-β superfamily, is a negative regulator of muscle growth and development. MYOD, a member of the myogenic regulatory factor family (MRFs), is a positive regulator of muscle growth and development. MSTN and MYOD interact to co-regulate muscle growth and development. In this study, we cloned the full-length cDNAs of mstn and myod in BY, analyzed differential expression of the two genes in muscle of BY and its parents, and observed the localization of the two genes during embryonic development of BY. Multiple sequence alignment of amino acids and phylogenetic analysis showed that mstn and myod were highly conserved in BY, BSB, YT, and other carp family fishes. Quantitative Real-time PCR (qRT-PCR) showed that mstn and myod were primarily expressed in muscle of BY, and there were significant differences in the expression of the two genes in the red and white muscles of BY, BSB, and YT at different age. The results of in situ hybridization of embryos showed an overlap in the temporal and spatial expression of mstn and myod in BY embryo development, suggesting that the two genes might interact to co-regulate embryo growth and development. This study provides a theoretical basis for further research on the mechanisms of mstn and myod in muscle growth of hybrid fishes.

Abstract Fluids released from subducting slabs profoundly affect mantle composition, rock melting points, and arc magma generation. However, identifying fluid sources (sediments, crust, or mantle) and their ascent paths remains challenging. Magnesium isotopes are potential tracers for subduction-related fluids, though their behavior during hydrous peridotite dehydration remains unclear. Here we determined the equilibrium magnesium isotope fractionation factors between aqueous fluids and hydrous peridotitic minerals using first-principles calculations. Aqueous fluids prefer heavy magnesium isotopes relative to mantle silicate minerals, indicating that fluids released during hydrous peridotite dehydration are enriched in heavy magnesium isotopes relative to the residual minerals. Our simulations proposed that magnesium isotope variations in arc lavas from different subduction zones could be attributed to different dehydration reactions influenced by subduction zone thermal structures. This study highlights the potential of magnesium isotopes for tracing fluids originating from subducting hydrated mantle, providing insights into the thermal structure of various subduction zones.

Abstract CircRNAs are a class of endogenous non-coding RNAs implicated in the pathogenesis of many pregnancy related diseases, one of which is pre-eclampsia (PE). This study aims to investigate the role of CircPAPPA2 (circbase ID: hsa_circ_0015382) in regulating the migration and invasion of trophoblast cells. RNA sequencing was used to identify the differentially expressed circRNAs in placenta of PE and normal pregnant women. Quantitative polymerase chain reaction (qRT-PCR) was used to verify the expression of circPAPPA2 and two miRNAs (miR-942-5p, 5006-3p) in placenta of PE and normal pregnant women. CCK8 and transwell experiments were performed to assess the function of circPAPPA2 in PE development.The interaction between circPAPPA2 and miR-942-5p/miR-5006-3p was verified by dual-luciferase reporter assay. Finally, bioinformatics analyzed with gene ontology, Kyoto Encyclopedia of the target genes. The results showed that the expression of circPAPPA2 was increased in placenta of PE pregnant women. Also, circPAPPA2 impedes trophoblasts cell proliferation and invasion. Moreover, the expression of circPAPPA2 was positively correlated with systolic blood pressure and urine protein. In addition, circPAPPA2 serves as a sponge of miR-942-5p and miR-5006-3p. In conclusion, CircPAPPA2 regulates trophoblasts cell proliferation and invasion by mediating the miR-942/miR-5006-3p.

Abstract Polymer-based pure organic room-temperature phosphorescent materials have tremendous advantages in applications owing to their low cost, vast resources, and easy processability. However, designing polymer-based room-temperature phosphorescent materials with large Stokes shifts as key requirements in biocompatibility and environmental-friendly performance is still challenging. By generating charge transfer states as the gangplank from singlet excited states to triplet states in doped organic molecules, we find a host molecule (pyrrolidone) that affords charge transfer with doped guest molecules, and excellent polymer-based organic room-temperature phosphorescent materials can be easily fabricated when polymerizing the host molecule. By adding polyaromatic hydrocarbon molecules as electron-donor in polyvinylpyrrolidone, efficient intersystem crossing and tunable phosphorescent from green to near-infrared can be achieved, with maximum phosphorescence wavelength and lifetime up to 757 nm and 3850 ms, respectively. These doped polyvinylpyrrolidone materials have good photoactivation properties, recyclability, advanced data encryption, and anti-counterfeiting. This reported design strategy paves the way for the design of polyvinylpyrrolidone-based room-temperature phosphorescent materials.

Abstract Acute cerebral ischemia has a high rate of disability and death. Although timely recanalization therapy may rescue the ischemic brain tissue, cerebral ischemia-reperfusion injury has been shown to limit the therapeutic effects of vascular recanalization. Protein HAX-1 has been reported as a pro-survival protein that plays an important role in various disorders, particularly in association with the nervous system. However, the effects and mechanisms of HAX-1 in cerebral IR injury have yet to be elucidated. So, we aimed to investigate the effect of HAX-1 on microglial pyroptosis and explore its potential neuroprotective effects in ischemia-reperfusion injury. Our results show that the expression of HAX-1 decreased after cerebral IR injury, accompanied by an increase in pyroptosis pathway activation. In addition, HAX-1 could inhibit microglial pyroptosis both in vivo and in vitro and reduce the release of inflammatory mediators. The above neuroprotective effects might be partially mediated by inhibiting of interaction of NLRP3 and ASC through competitive binding, followed by the attenuation of NLRP3 inflammasome formation. In conclusion, Our findings support that HAX-1 exhibits a protective role in cerebral I/R injury, and further study on HAX-1 expression regulation will contribute to cerebral infarction therapy.

Abstract Background The feasibility and safety of laparoscopic pancreatoduodenectomy (LPD) in elderly patients is still controversial. This study aimed to compare the clinical outcomes of LPD and open pancreatoduodenectomy (OPD) in elderly patients. Methods Clinical and follow-up data of elderly patients (≥ 65 years) who underwent LPD or OPD between 2015 and 2022 were retrospectively analyzed. A 1:1 propensity score-matching (PSM) analysis was performed to minimize differences between groups. Univariate and multivariate logistic regression analysis were used to select independent prognostic factors for 90-day mortality. Results Of the 410 elderly patients, 236 underwent LPD and 174 OPD. After PSM, the LPD group had a less estimated blood loss (EBL) (100 vs. 200 mL, P 0.05). Multivariate logistic regression analysis showed that post-pancreatectomy hemorrhage (PPH) was an independent risk factor for 90-day mortality. Elderly patients with pancreatic ductal adenocarcinoma (PDAC) who underwent LPD or OPD had similar overall survival (OS) (22.5 vs.20.4 months, P = 0.672) after PSM. Conclusions It is safe and feasible for elderly patients to undergo LPD with less EBL and a shorter postoperative LOS. There was no statistically significant difference in long-term survival outcomes between elderly PDAC patients who underwent LPD or OPD.

IntroductionChina’s rural financial landscape has long been characterized by exclusion, leaving countless farmers without access to essential financial services. However, the advent of digital financial inclusion presents a promising solution, offering low-cost, high-penetration avenues to bolster agricultural sustainability. This paper unravels how “Byte-Sized Finance” can yield “Bushel-Sized Benefits” in China’s agricultural green development.MethodsMethodologically, we pioneer a novel system to gauge agricultural green development across 31 Chinese provinces spanning from 2013 to 2021. Empirically, employing fixed-effect, mediation effect, and spatial Durbin models.ResultsOur study reveals the intricate pathways through which digital financial inclusion influences agricultural green development. We find that it exerts its impact through the lenses of industrial structure and entrepreneurship, operating at both macro and micro levels. Furthermore, our analysis uncovers spatial spillover effects, shedding light on the differential roles played by these mechanisms across regions.DiscussionThis groundbreaking discovery underscores the transformative potential of leveraging digital financial inclusion to propel China toward agricultural green development. By shedding light on these crucial dynamics, our findings offer insights for policymakers, researchers, and practitioners striving to foster sustainability within China’s agricultural sector.

The EIN3/EIL gene family holds a pivotal role as it encodes a crucial transcription factor in plants. During the process of polyploidization in broomcorn millet (Panicum miliaceum L.), there is an intriguing above-average amplification observed within the EIN3/EIL gene family. Nonetheless, our current knowledge of this gene family in broomcorn millet remains limited. Hence, in this study, we conducted a comprehensive analysis of the EIN3/EIL gene family in broomcorn millet, aiming to provide a deeper understanding of the potential evolutionary changes. Additionally, we analyzed the EIN3/EIL gene family of Panicum hallii L., a close relative of broomcorn millet, to enhance our characterization efforts. Within this study, we identified a total of 15 EIN3/EIL genes specific to broomcorn millet. Through covariance analysis, it was revealed that all PmEIL genes, except PmEIL1 and PmEIL15, had duplicate copies generated through genome-wide duplication events. Importantly, the Ka/Ks values of all duplicated genes were found to be less than 1, indicating strong purifying selection. Phylogenetic analysis showed that these genes could be categorized into four distinct evolutionary branches, showcasing similar characteristics among members within the same branch. However, there appeared to be an uneven distribution of cis-acting elements amid the EIN3/EIL genes. Further examination of transcriptomic data shed light on the diverse spatiotemporal and stress-related expression patterns exhibited by the EIN3/EIL genes in broomcorn millet. Notably, under cold stress, the expression of PmEIL3/4/8/14 was significantly up-regulated, while under drought stress, PmEIL4/5/6 displayed significant up-regulation. Intriguingly, the expression pattern of PmEIL15 showed an opposite pattern in resistant and sensitive cultivars. The findings of this study augment our understanding of the EIN3/EIL gene family in broomcorn millet and offer a valuable reference for future investigations into polyploid studies. Moreover, this study establishes a theoretical foundation for further exploration of the ethylene signaling pathway in broomcorn millet.

Summary: Constipation and frailty are associated with intestinal dysbiosis. This study aims to identify intestinal microbial signatures that can differentiate between constipated elders accompanied by frailty and those without frailty. We collected stool samples from 61 participants and conducted 16S rRNA gene sequencing. Constipated patients with frailty (Constipation_F) exhibited reduced gut microbial diversities compared to constipated patients without frailty (Constipation_NF) and healthy individuals (C). From differential genera, random forest models identified 14, 8, and 5 biomarkers for distinguishing Constipation_F from Constipation_NF, Constipation_F from C, and Constipation_NF from C, respectively. Functional analysis revealed that pathways (P381-PWY and PWY-5507) related to vitamin B12 synthesis were reduced in Constipation_F, which aligns with the decreased abundances of vitamin-B12-producing Actinomyces and Akkermansia in this group. Our study unveils substantial differences in gut microbiota between constipated elders with frailty and those without, underscoring the diagnostic and therapeutic potential of genera involved in vitamin B12 synthesis.

Multidrug resistant bacteria have been a global health threat currently and frontline clinical treatments for these infections are very limited. To develop potent antibacterial agents with new bactericidal mechanisms is thus needed urgently to address this critical antibiotic resistance challenge. Natural products are a treasure of small molecules with high bioactive and low toxicity. In the present study, we demonstrated that a natural compound, honokiol, showed potent antibacterial activity against a number of Gram-positive bacteria including MRSA and VRE. Moreover, honokiol in combination with clinically used β-lactam antibiotics exhibits strong synergistic antimicrobial effects against drug-resistant S. aureus strains. Biochemical studies further reveal that honokiol may disrupt the GTPase activity, FtsZ polymerization, cell division. These biological impacts induced by honokiol may ultimately cause bacterial cell death. The in vivo antibacterial activity of honokiol against S. aureus infection was also verified with a biological model of G. mellonella larvae. The in vivo results support that honokiol is low toxic against the larvae and effectively increases the survival rate of the larvae infected with S. aureus. These findings demonstrate the potential of honokiol for further structural advancement as a new class of antibacterial agents with high potency against multidrug-resistant bacteria.

The global mental health crisis presents a significant challenge to sustainable development, and this crisis is more pronounced in China's rural areas versus urban areas. Alcohol consumption has increased in rural areas with China's economic growth, but the number of studies on the relationship between farmers' alcohol consumption and their mental health is limited. Based on data from the China Labor Force Dynamics Survey (CLDS), this study uses the endogenous switching regression model (ESR) to analyze the influence of alcohol consumption on farmers' mental health. On this basis, the study further conducts a counterfactual analysis to estimate the average treatment effect of alcohol consumption on farmers' mental health. The results show that: (1) There is a significant positive relationship between alcohol consumption and farmers' mental health. Specifically, the mental health index of drinking farmers increases by 19.7 % compared to non-drinking farmers. (2) Heterogeneity analysis shows that alcohol consumption is more beneficial for improving the mental health of male farmers, elderly farmers, and employed farmers. Furthermore, drinking alcohol almost every day, consuming Baijiu, and each drinking consumption ranging from 0 to 100 mL per occasion are more conducive to improving farmers' mental health. These findings have implications for relieving depressive symptomology and improving farmers' mental health in developing countries. The results of this study also provide guidance for addressing the global mental health crisis.

Abstract Proper differentiation of corneal epithelial cells (CECs) from limbal stem/progenitor cells (LSCs) is required for maintenance of ocular homeostasis and clear vision. Here, using a single-cell transcriptomic atlas, we delineate the comprehensive and refined molecular regulatory dynamics during human CEC development and differentiation. We find that RORA is a CEC-specific molecular switch that initiates and drives LSCs to differentiate into mature CECs by activating PITX1. RORA dictates CEC differentiation by establishing CEC-specific enhancers and chromatin interactions between CEC gene promoters and distal regulatory elements. Conversely, RORA silences LSC-specific promoters and disrupts promoter-anchored chromatin loops to turn off LSC genes. Collectively, our work provides detailed and comprehensive insights into the transcriptional dynamics and RORA-mediated epigenetic remodeling underlying human corneal epithelial differentiation.

Using recycled concrete fines (RFs) as a supplementary cementitious material in blended cement systems offers potential benefits for the construction industry. This study investigated the mechanical properties, hydration development, and microstructural evolutions of blended Portland cement systems incorporating different particle-size distributions of untreated RFs. The results highlighted that finer RFs improved the compressive strength of mortar and influenced hydration by promoting monocarbonate formation. The incorporation of RFs optimizes the pore structure in the early stage but increases porosity. RFs affected the distribution of capillary pores and created a rougher and more complex surface compared to inert mineral admixtures. Furthermore, the particle size of RFs impacted the fractal dimension of multi-scale pore sizes.

Key Clinical Message The most frequently reported adverse reaction to zoledronic acid is an acute phase reaction resembling influenza. While rarer adverse events such as osteonecrosis of the jaw and atypical femoral fractures have gained significant recognition, the ocular adverse effects, particularly scleritis, are not yet fully comprehended. Here, we present the case of a 75‐year‐old female patient with osteoporosis who developed bilateral redness and intense eye pain 48 h after receiving a 5 mg intravenous dose of zoledronic acid. Clinical presentation suggested bilateral conjunctivitis, but treatment with levofloxacin eye drops and acyclovir ophthalmic gel exacerbated the symptoms over 2 days, predominantly affecting the left eye. Ocular ultrasonography revealed thickening of the left eyeball wall with a “T” sign, while an orbital CT scan showed increased thickness of the left sclera. Treatment with methylprednisolone 80 mg intravenous infusion twice daily led to gradual symptom improvement and eventual resolution of inflammation. This report, based on a review of relevant literature, investigates the treatment and outcomes of zoledronic acid‐induced scleritis, emphasizing the importance for clinicians to promptly identify and manage this rare and serious ocular adverse reaction.

Abstract Diabetes mellitus (DM) is a common chronic disease affecting humans globally. It is characterized by abnormally elevated blood glucose levels due to the failure of insulin production or reduction of insulin sensitivity and functionality. Insulin and glucagon‐like peptide (GLP)‐1 replenishment or improvement of insulin resistance are the two major strategies to treat diabetes. Recently, optogenetics that uses genetically encoded light‐sensitive proteins to precisely control cell functions has been regarded as a novel therapeutic strategy for diabetes. Here, we summarize the latest development of optogenetics and its integration with synthetic biology approaches to produce light‐responsive cells for insulin/GLP‐1 production, amelioration of insulin resistance and neuromodulation of insulin secretion. In addition, we introduce the development of cell encapsulation and delivery methods and smart bioelectronic devices for the in vivo application of optogenetics‐based cell therapy in diabetes. The remaining challenges for optogenetics‐based cell therapy in the clinical translational study are also discussed.

IntroductionWith improvements in living conditions, modern individuals exhibit a pronounced inclination towards a high-fat diet, largely because of its distinctive gustatory appeal. However, the association between high-fat diets and metabolic complications has largely been ignored, and metabolic diseases such as obesity and non-alcoholic fatty liver disease now constitute a major public health concern. Because high-fat diets increase the risk of metabolic diseases, a thorough investigation into the impact of high-fat diets on gut microbiota and metabolism is required.MethodsWe utilize 16S rRNA sequencing and untargeted metabolomics analysis to demonstrate that SD rats fed a high-fat diet exhibited marked alterations in gut microbiota and plasma, intestinal metabolism.ResultsChanges in gut microbiota included a decreased abundance at phylum level for Verrucomicrobiota, and a decreased abundance at genus level for Akkermansia, Ralstonia, Bacteroides, and Faecalibacterium. Additionally, significant changes were observed in both intestinal and plasma metabolite levels, including an upregulation of bile acid metabolism, an upregulation of glucose-lipid metabolism, and increased levels of metabolites such as norlithocholic acid, cholic acid, D-fructose, D-mannose, fructose lactate, and glycerophosphocholine. We also investigated the correlations between microbial communities and metabolites, revealing a significant negative correlation between Akkermansia bacteria and cholic acid.DiscussionOverall, our findings shed light on the relationship between symbiotic bacteria associated with high-fat diets and metabolic biomarkers, and they provide insights for identifying novel therapeutic approaches to mitigate disease risks associated with a high-fat diet.

Abstract Background Drought is one of the main consequences of global climate change and this problem is expected to intensify in the future. Resurrection plants evolved the ability to withstand the negative impact of long periods of almost complete desiccation and to recover at rewatering. In this respect, many physiological, transcriptomic, proteomic and genomic investigations have been performed in recent years, however, few epigenetic control studies have been performed on these valuable desiccation-tolerant plants so far. Results In the present study, for the first time for resurrection plants we provide evidences about the differential chromatin accessibility of Haberlea rhodopensis during desiccation stress by ATAC-seq (Assay for Transposase Accessible Chromatin with high-throughput sequencing). Based on gene similarity between species, we used the available genome of the closely related resurrection plant Dorcoceras hygrometricum to identify approximately nine hundred transposase hypersensitive sites (THSs) in H. rhodopensis. The majority of them corresponds to proximal and distal regulatory elements of different genes involved in photosynthesis, carbon metabolism, synthesis of secondary metabolites, cell signalling and transcriptional regulation, cell growth, cell wall, stomata conditioning, chaperons, oxidative stress, autophagy and others. Various types of binding motifs recognized by several families of transcription factors have been enriched from the THSs found in different stages of drought. Further, we used the previously published RNA-seq data from H. rhodopensis to evaluate the expression of transcription factors putatively interacting with the enriched motifs, and the potential correlation between the identified THS and the expression of their corresponding genes. Conclusions These results provide a blueprint for investigating the epigenetic regulation of desiccation tolerance in resurrection plant H. rhodopensis and comparative genomics between resurrection and non-resurrection species with available genome information.

Unmanned aerial vehicle (UAV) confrontation scenarios play a crucial role in the study of agent behavior selection and decision planning. Multi-agent reinforcement learning (MARL) algorithms serve as a universally effective method guiding agents toward appropriate action strategies. They determine subsequent actions based on the state of the agents and the environmental information that the agents receive. However, traditional MARL settings often result in one party agent consistently outperforming the other party due to superior strategies, or both agents reaching a strategic stalemate with no further improvement. To solve this issue, we propose a semi-static deep deterministic policy gradient algorithm based on MARL. This algorithm employs a centralized training and decentralized execution approach, dynamically adjusting the training intensity based on the comparative strengths and weaknesses of both agents’ strategies. Experimental results show that during the training process, the strategy of the winning team drives the losing team’s strategy to upgrade continuously, and the relationship between the winning team and the losing team keeps changing, thus achieving mutual improvement of the strategies of both teams. The semi-static reinforcement learning algorithm improves the win-loss relationship conversion by 8% and reduces the training time by 40% compared with the traditional reinforcement learning algorithm.

Although considered a crucial component of the Rodinia supercontinent, it remains uncertain how the Yangtze craton relates to the accretion and breakup of Rodinia. Here, the Huanglingmiao granitic complex (HGC), an intermediate-acid rock series that intruded on the southern Kongling terrane of the northern Yangtze craton margin, is investigated to help resolve this conundrum. Our analysis indicates that these rocks consist of tonalite, trondhjemite, granodiorite, oligoporphyritic granodiorite, porphyric biotite granodiorite, and fine- to medium-grained granodiorite dyke compositions. Collectively, this assemblage is further subdivided into two categories by their temporal, spatial, and geochemical features into early TTG-like and later granitic–dioritic units, which are composed of tonalite, trondhjemite, granodiorite, porphyritic granodiorite, and the fine- to medium-grained granodiorite dykes, respectively. Zircon U-Pb dating yields ages of 865~850 Ma for the TTG-like rocks, 844~825 Ma for the porphyritic granodiorites, and ~800 Ma for the granodiorite dykes. Combined with geochemical evidence, the data suggest that the early- and late-series rocks were formed by a partial melting of Mesoproterozoic and Paleoproterozoic crustal materials, respectively, suggesting that the vertical layering of the crust controlled the composition of the independent units. In addition, isotopic evidence points to different sources for the various rocks in the Kongling terrane and that mantle-derived materials influenced the early-series lithologies. Combined with previous studies on the northern margin of the Yangtze craton, it is inferred that the early-series rocks formed in an active continental margin environment, while the late-series rocks display within-plate boundary formation characteristics. The multiple magmatic activities revealed by this study record sequential partial melting with tectonic transition characteristics from an Andean-type to within-plate magmatism in the northern margin of the Yangtze craton. Taken together, these observations point to a strong association between these rocks, convergence, and incorporation of the northern Yangtze craton margin into the Rodinia supercontinent during the Tonian Period.

Non-structural carbohydrates (NSC) are an important “buffer” for maintaining plant physiological functions under drought conditions; however, our understanding of the dynamics of NSC at the organ level during sustained drought of varying intensities and re-watering remains poor. In this study, two-year-old Pinus yunnanensis seedlings were subjected to drought and re-watering trials. Plants were subjected to three drought intensities (light drought, moderate drought, and severe drought) as well as control conditions (suitable moisture) for 51 days, including 30 days of drought followed by 21 days of re-watering for drought-treated seedlings, to study the dynamics of NSC in the leaves, stems, coarse roots, and fine roots. Changes in the distribution of NSC concentrations in the organ of P. yunnanensis seedlings under drought stress varied; in the early drought stages, the drought resistance of P. yunnanensis seedlings was enhanced by increasing soluble sugar concentrations; in later stages of drought, the stored starch in organs, stems, and coarse roots was consumed. Drought inhibited the growth of P. yunnanensis seedlings, but the maximum limit of drought tolerance was not reached under the different drought treatments after 30 days. P. yunnanensis seedlings in all treatment groups resumed growth after re-watering, and the growth of seedlings was actually promoted during re-watering in the moderate drought treatment group, indicating that drought induced the compensatory growth of seedlings. The growth of P. yunnanensis seedlings during re-watering was inhibited in the severe drought treatment group, and NSC continued to be regulated in seedlings in this group. Given that P. yunnanensis seedlings maintain growth through the consumption of coarse root starch in the late stages of drought, seedlings with a larger root-to-shoot ratio should be selected for cultivation in actual production. Based on our findings, exposure to moderate drought stress can enhance the drought tolerance of P. yunnanensis seedlings and promote the compensatory growth of seedlings.

Global climate changes have led to severe and frequent drought stress in many areas, seriously threatening the stability of yield in wheat. Exploring the quantitative trait loci for yield stability under drought condition is needed for wheat molecular breeding. In this study, we collected a panel of 432 diverse wheat accessions from different regions around the world and evaluated the drought stress susceptibility index of wheat yield-related phenotypes under drought stress and genotyped the panel with the wheat660K SNP array. Genome-wide association analysis has identified 40 yield stability-related loci, which distribute on various chromosomes. Four loci on Chromosome 1 A, 2B, 3 A and 7B are associate with more than two phenotypic indicators, explaining 1.59% − 8.07% of the phenotypic variation. Among them, Qgns.cas-3A.2 is a novel QTL for wheat yield stability under drought stress. Venn diagram analysis on the drought-responsive expression patterns of Qtgw.cas-3A genes in drought-tolerant and sensitive cultivars, and linkage disequilibrium analysis of the 57Kb region flanking SNP marker AX-108784842 on chromosomes 3 A which displays the highest confidence identified the same candidate gene, which encodes a glycosyl hydrolases family 17 protein. Haplotype analysis indicated that GG allele of this gene is the favorable allele for wheat yield stability under drought. Taken together, these results provide new insights on understanding the genetic basis of wheat yield stability under drought stress and new tools for developing molecular markers to engineer drought-tolerant wheat cultivars.

With continually increasing urbanization, the land cover in urban areas continues to change, resulting in the loss of biodiversity. Birds are highly sensitive to changes in habitat. Most forest birds perch on plants that provide increased safety to reduce the risk of predation, and small birds may also consider insulation when using roosting plants in winter because of cold weather. Landscaping plants thus shape the nocturnal roosting environment of urban birds, and proper planting is essential for the survival of birds at night. The use of roosting plants by urban birds should therefore be studied to provide a reference for landscaping. In the current study, we observed 1865 nocturnal roosting birds in Beijing from 2021 to 2022, with 23 species of birds from 12 families and 45 species of plants from 22 families recorded. Juniperus chinensis exhibited the highest bird rarity-weighted richness, followed by Fraxinus pennsylvanica, Phyllostachys propinqua, Pinus tabuliformis, and Ulmus pumila. The diameter at breast height, tree height, and crown width of plants used by birds was largest in summer and smallest in winter, and the perch height of birds was the highest in spring and summer and the lowest in winter. Birds used the highest proportion of deciduous plants in summer and the highest proportion of evergreen plants in winter. A significant seasonal difference in the use of evergreen and deciduous plants by small birds was noted, with a preference for deciduous plants in summer and evergreen plants in winter, while this preference was not found in large birds. These findings indicate that evergreen plants provide a vital nocturnal roosting environment for small birds in winter. To provide a better nocturnal roosting habitat for urban birds, we recommend paying attention to the combination of evergreen and deciduous plants when carrying out landscape construction.

Mitochondria are not only the power plant for intracellular oxidative phosphorylation and ATP synthesis, but also involved in cell proliferation, differentiation, signaling and apoptosis. Recent studies have shown that mitochondria play an important role in other pathophysiological functions in addition to cellular energy metabolism. Mitochondria release mitochondrial DNA (mtDNA) as a damage-associated molecular pattern (DAMP) to activate Toll-like receptor 9 (TLR9), NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) innate immune signaling pathways against foreign pathogenic microorganisms. The innate immune response not only promotes antimicrobial immune defense and regulates antiviral signaling, but their overactivation also induces the onset and progression of inflammatory diseases. In this paper, we review the role of mtDNA in the activation of innate immune signaling pathways and the crosstalk among innate immune signaling pathways activated by mtDNA, providing clues for the study of inflammatory diseases caused by mtDNA cytoplasmic translocation.

BackgroundMelanocortin-3 and -4 receptors (MC3R and MC4R), G protein-coupled receptors, play vital roles in the regulation of energy homeostasis. To understand the functions of mc3r and mc4r in the energy homeostasis of red crucian carp (Carassius auratus red var., RCC), we cloned mc3r and mc4r, analyzed the tissue expression and localization of the genes, and investigated the effects of knockout of mc3r (mc3r+/-) and mc4r (mc4r+/-) in RCC. ResultsThe full-length cDNAs of RCC mc3r and mc4r were 1459 base pairs (bp) and 1894 bp, respectively. qRT-PCR indicated that mc3r and mc4r were profusely expressed in the brain, but lower expressed in the periphery tissues. ISH revealed that mc3r and mc4r were located in NPP, NPO, NAPv, NSC, NAT, NRL, NLTl, and NLTp of the brain, suggesting that mc3r and mc4r might regulate many physiological and behavioral aspects in RCC. To further verify the roles of mc3r and mc4r in energy homeostasis, the mc3r+/- and mc4r+/- fish were obtained by the CRISPR/Cas9 system. The average body weights, total lengths, body depths, and food intake of mc4r+/- fish were significantly higher than those of mc3r+/- and the normal wild-type (WT) fish, but there was no difference between the mc3r+/- and WT fish, indicating that the RCC phenotype and food intake were mainly influenced by mc4r but not mc3r. Interestingly, mc4r+/- fish displayed more visceral fat mass than mc3r+/- and WT fish, and mc3r+/- fish also exhibited slightly more visceral fat mass compared to WT. RNA-seq of the liver and muscle revealed that a large number of differentially expressed genes (DEGs) differed in WT vs. mc3r+/-, WT vs. mc4r+/-, and mc3r+/- vs. mc4r+/-, mainly related to lipid, glucose, and energy metabolism. The KEGG enrichment analysis revealed that DEGs were mainly enriched in pathways such as steroid biosynthesis, fatty acid metabolism, fatty acid biosynthesis, glycolysis/gluconeogenesis, wnt signaling pathway, PPAR signaling pathway, and MAPK signaling pathway, thereby affecting lipid accumulation and growth. ConclusionIn conclusion, these results will assist in the further investigation of the molecular mechanisms in which MC3R and MC4R were involved in the regulation of energy homeostasis in fish.

Background: The aim of this study was to evaluate the accuracy of LiveBoost™, a gradient boosting (GB)-based prediction system based on standard biochemical values (AST, ALT, platelet count) and age, in Chinese patients with chronic hepatitis B (CHB) and compare its performance with FIB-4 (fibrosis-4 score) and APRI (the aspartate transaminase to platelet ratio index). Methods: This retrospective trial enrolled 454 participants, including 279 CHB patients who underwent liver biopsy and 175 normal controls from 3 centers in China. All participants underwent laboratory blood testing. LiveBoost was constructed using GB and FIB-4 and APRI were calculated from laboratory data. Results: LiveBoost outperformed APRI and FIB-4 in predicting hepatic fibrosis and cirrhosis. The GB model had an AUROC of 0.977 for CHB diagnosis, 0.804 for early and advanced fibrosis, and 0.836 for non-cirrhosis and cirrhosis, compared to AUROC of 0.554, 0.673 and 0.720 for FIB-4, AUROC of 0.977, 0.652 and 0.654 for APRI. Conclusions: LiveBoost is a more reliable and cost-effective method than APRI and FIB-4 for assessing liver fibrosis in Chinese patients with CHB.

Background and objectiveThe safety and efficacy of on-label use of pipeline embolization devices (PEDs) are well established; however, there is much controversy over their off-label use. This study aimed to investigate the safety and efficacy of the off-label use of PEDs for treating intracranial aneurysms.MethodsThis single-center study retrospectively included patients with digital subtraction angiography, computed tomographic angiography, or magnetic resonance angiography confirmed intracranial aneurysms treated with PEDs who were admitted to our institution between 1 January 2018 and 1 July 2022. Patients were divided into on- and off-label groups according to the Food and Drug Administration criteria published in 2021. Propensity score matching (PSM) was used to balance disparities in baseline information between the two groups. Safety outcomes included postoperative mortality and complication rates, whereas effectiveness outcomes included aneurysm occlusion rate (O’Kelly-Marotta grading system C + D grades), retreatment rate within 12 months, and postoperative functional score [modified Rankin scale (mRS) score]. The study was approved by the Ethics Committee of Scientific Research and Clinical Trial of the First Affiliated Hospital of Zhengzhou University (Ethics number: KY 2018–098-02). All patients provided informed consent.ResultsA total of 242 patients with 261 aneurysms (160 on-label and 101 off-label aneurysms) were included in this study. PSM yielded 81 pairs of patients matched for baseline information. Postoperative hemorrhagic, ischemic, and procedure-related complication rates did not reach statistical significance. In addition, no statistically significant differences in the aneurysm occlusion rate, retreatment rate within 12 months, postoperative functional score (mRS score), or mRS score deterioration rate were observed between the two groups. A higher incidence of in-stent stenosis was observed in the off-label (4.9% vs. 21%, p = 0.002) group than in the on-label group; however, all patients were asymptomatic.ConclusionCompared with on-label use, off-label use of PEDs for treating intracranial aneurysms did not increase the risk of complications, and the occlusion rates were comparable. Therefore, decisions regarding clinical management should not rely solely on on- or off-label indications.

Background: Inflammatory bowel diseases (IBD), such as severe colitis, are associated with the development of lung inflammation and tissue damage. Pueraria lobata (P. lobata) plays an essential role in controlling cytokines. However, the exact mechanism of the inflammation response is still unknown. Purpose: To investigate the effects of the P. lobata-derived exosomes-like nanovesicles (PLDENs) on colitis and their role in the lung inflammatory response. Methods: In this study, we investigated the effects of PLDENs on the dextran sulfate sodium (DSS)-induced colitis and explored the mechanisms by forming the gut-lung axis. PLDENs were characterized by mass spectrometry-based proteomic analysis. Results: The results showed that PLDENs had significant preventive effects in DSS-induced colitis and pathological changes in colons in a dose-dependent manner. Simultaneously, the treatment of PLDENs could effectively reduce inflammatory changes in the lung. PLDENs could selectively regulate the composition of gut microbiota. Conclusion: These data suggested that the treatment of PLDENs could ‘attenuate DSS-induced colitis and lung inflammation, providing an efficacious supplement for reducing co-morbidities in IBD patients.

Abstract Background A new antibacterial compound powder of amoxicillin (AMO)/Radix Scutellaria extract (RSE) was developed, and its pharmacokinetics were determined in pigs following oral administration. Results The MIC ranges of AMO against Escherichia coli, Staphylococcus aureus and Streptococcus were 1–8 μg/mL, 0.5–4 μg/mL and 0.5–64 μg/mL, respectively. The MIC ranges of RSE against E. coli, S. aureus, and Streptococcus were greater than 2.5 mg/mL, 0.156–2.5 mg/mL, and greater than 2.5 mg/mL, respectively. For S. aureus, the combined drug susceptibility test showed that AMO and RSE had an additive or synergistic effect. The results of compatibility test, the excipient screening test and the drug quality control test showed that the formulation had stable quality and uniform properties under the test conditions. Two studies were conducted to investigate the pharmacokinetics of the compound product in pigs. First, the pharmacokinetics of the AMO-RSE powder were compared with those of their respective single products. The results showed no significant change in the main pharmacokinetic parameters when either component was removed from the compound formulation; thus, AMO and RSE have no pharmacokinetic interaction in pigs. Second, pigs were orally administered three different doses of AMO-RSE powder. The Cmax and AUC increased proportionally with increasing p.o. dose; thus, the λz, t1/2λ, MRT, and Tmax were unchanged for the doses of 10, 20, and 30 mg/kg AMO and the doses of 5, 10, and 15 mg/kg BCL, showing that AMO/baicalin in AMO-RSE powder showed linear pharmacokinetic characteristics in pigs. Conclusions The combined drug sensitivity test of AMO and RSE against S. aureus showed that the combination was additive or synergistic. Pharmacokinetic studies indicated that AMO and BCL do not interfere with each other in pigs when used in a compound formulation. The pharmacokinetic parameters remained unchanged regardless of the dose for p.o. administration, indicating linear pharmacokinetic properties over the tested dose range. The quality of the AMO-RSE powder was good and stable, providing a foundation for its clinical application in veterinary medicine. Further bioavailability, PK/PD and clinical trials are still needed to determine the final dosage regimen.

In Pseudomonas aeruginosa (P. aeruginosa), transcription factors (TFs) are important mediators in the genetic regulation of adaptability and pathogenicity to respond to multiple environmental stresses and host defences. The P. aeruginosa genome harbours 371 putative TFs; of these, about 70 have been shown to regulate virulence-associated phenotypes by binding to the promoters of their target genes. Over the past three decades, several techniques have been applied to identify TF binding sites on the P. aeruginosa genome, and an atlas of TF binding patterns has been mapped. The virulence-associated regulons of TFs show complex crosstalk in P. aeruginosa's regulatory network. In this review, we summarise the recent literature on TF regulatory networks involved in the quorum-sensing system, biofilm formation, pyocyanin synthesis, motility, the type III secretion system, the type VI secretion system, and oxidative stress responses. We discuss future perspectives that could provide insights and targets for preventing clinical infections caused by P. aeruginosa based on the global regulatory network of transcriptional regulators.

Abstract The conversion of lignocellulosic feedstocks to fermentable sugar for biofuel production is inefficient, and most strategies to enhance efficiency directly target lignin biosynthesis, with associated negative growth impacts. Here we demonstrate, for both laboratory- and field-grown plants, that expression of Pag-miR408 in poplar (Populus alba × P. glandulosa) significantly enhances saccharification, with no requirement for acid-pretreatment, while promoting plant growth. The overexpression plants show increased accessibility of cell walls to cellulase and scaffoldin cellulose-binding modules. Conversely, Pag-miR408 loss-of-function poplar shows decreased cell wall accessibility. Overexpression of Pag-miR408 targets three Pag-LACCASES, delays lignification, and modestly reduces lignin content, S/G ratio and degree of lignin polymerization. Meanwhile, the LACCASE loss of function mutants exhibit significantly increased growth and cell wall accessibility in xylem. Our study shows how Pag-miR408 regulates lignification and secondary growth, and suggest an effective approach towards enhancing biomass yield and saccharification efficiency in a major bioenergy crop.

Abstract Background Hip fractures are common in elderly patients, and almost all the patients undergo surgery. This study aimed to develop a novel modified lymphocyte C-reactive protein (CRP) score (mLCS) to simply and conveniently predict 3-year mortality in elderly patients undergoing intertrochanteric fracture surgery. Methods A retrospective study was conducted on elderly patients who underwent intertrochanteric fracture surgery between January 2014 and December 2017. The mLCS was developed according to the value of CRP and lymphocyte counts. Univariate and multivariate Cox regression analyses were used to identify independent risk factors for 3-year mortality after surgery. The performances of the lymphocyte CRP score (LCS) and mLCS to predict 3-year mortality were then compared using C-statistics, decision curve analysis (DCA), net reclassification index (NRI) and integrated discrimination improvement (IDI). Results A total of 291 patients were enrolled, of whom 52 (17.9%) died within 3 years after surgery. In the multivariate Cox regression analysis, mLCS (hazard ratio (HR), 5.415; 95% confidence interval (CI), 1.743–16.822; P = 0.003) was significantly associated with postoperative 3-year mortality. The C-statistics of LCS and mLCS for predicting 3-year mortality were 0.644 and 0.686, respectively. The NRI (mLCS vs. LCS, 0.018) and IDI (mLCS vs. LCS, 0.017) indicated that the mLCS performed better than the LCS. DCA also showed that mLCS had a higher clinical net benefit. Conclusions mLCS is a promising predictor that can simply and conveniently predict 3-year mortality in elderly patients undergoing intertrochanteric fracture surgery.

Small molecules are significant risk factors for causing food safety issues, posing serious threats to human health. Sensitive screening for hazards is beneficial for enhancing public security. However, traditional detection methods are unable to meet the requirements for the field screening of small molecules. Therefore, it is necessary to develop applicable methods with high levels of sensitivity and specificity to identify the small molecules. Aptamers are short−chain nucleic acids that can specifically bind to small molecules. By utilizing aptamers to enhance the performance of recognition technology, it is possible to achieve high selectivity and sensitivity levels when detecting small molecules. There have been several varieties of aptamer target recognition techniques developed to improve the ability to detect small molecules in recent years. This review focuses on the principles of detection platforms, classifies the conjugating methods between small molecules and aptamers, summarizes advancements in aptamer−based conjugate recognition techniques for the detection of small molecules in food, and seeks to provide emerging powerful tools in the field of point−of−care diagnostics.

High-density building environments and fast-paced working conditions in cities pose health challenges for office workers. Office-type pocket parks assume the social responsibility of providing restorative environments for office workers, and the soundscape is an essential element of such environments. However, there is limited research on soundscape restoration in office-type pocket parks. Therefore, this study focused on soundscape restoration in office-type pocket parks. First, on-site investigations explored the spatial characteristics of 55 office-type pocket parks while analysing the soundscape features of 12 representative parks. Notably, significant correlations emerged among the perceptual parameters of the soundscape. Subsequently, three dimensions were extracted through an experimental study on the restoration levels of soundscape elements in office-based pocket parks: attractiveness, coordination, and disengagement. Finally, this study explored the impact of spatial enclosures and interface characteristics on soundscape restoration levels. This revealed that the restorative effect of negative sounds, such as traffic, air-conditioning, and speech, is significantly negatively correlated with spatial enclosure. Therefore, the greater the enclosure, the lower the restorative effect of the soundscape. Birdsongs significantly enhance the attractiveness of grey spaces, whereas small fountain sounds are most coordinated in blue spaces. This study provides a reference for the design of soundscapes in pocket parks to build healthy, restorative urban environments.

The characteristics of C:N:P stoichiometry, nonstructural carbohydrate (NSC) content, and C stable isotopes and their relationships affect plant responses to environmental changes and are critical to understanding the ecosystem carbon and water cycles. We investigated the water use strategies and physiological changes of two pioneer tree species (Pinus armandii and Pinus yunnanensis) in response to seasonal drought in subtropical China. The seasonal variation in needle δ13C values, C:N:P stoichiometry, and NSC contents of the two tree species were studied in 25-year-old plantation in central Yunnan Province. The needle δ13C values of both species were highest in summer. Soluble sugars, starch and NSC content of the two tree species decreased from spring to winter, while there was no significant difference in the seasonal variation of soluble sugars/starch in P. armandii needles, the maximum soluble sugars/starch in P. yunnanensis needles was in autumn. In addition, the C, N, and P contents of the needles and the C:N and C:P ratios of the two species showed different seasonal fluctuations, whereas the N:P ratio decreased with the season. The C:N:P stoichiometry and NSC content of the needles showed significant correlations, whereas the needle δ13C was weakly correlated with C:N:P stoichiometry and NSC content. Phenotypic plasticity analysis and principal component analysis revealed that the needle nutrient characteristics (NSC and P contents and N:P ratio) and needle δ13C values were critical indicators of physiological adaptation strategies of P. armandii and P. yunnanensis for coping with seasonal variation. These results increase our understanding of the water-use characteristics of the two pioneer tree species and the dynamic balance between the NSC, C, N, and P contents of the needles.

Abstract Background Acute pancreatitis in pregnancy (APIP) with a high risk of death is extremely harmful to mother and fetus. There are few models specifically designed to assess the severity of APIP. Our study aimed to establish a clinical model for early prediction of severity of APIP. Methods A retrospective study in a total of 188 patients with APIP was enrolled. The hematological indicators, IAP (intra-abdominal pressure) and clinical data were obtained for statistical analysis and prediction model construction. Results According to univariate and multivariate logistic regression analysis, we found that red cell distribution width (RDW), neutrophil-lymphocyte ratio (NLR) and Intra-abdominal pressure (IAP) are prediction indexes of the severity in APIP (p-value

Tsunami wave characteristics are greatly influenced by the initial water level when they attack structures. In this study, experimental and numerical investigations were conducted to investigated the relationship between tsunami wave characteristics and initial water levels. Results showed that, the wave height, wave velocity, and Froude number increase with the increase of tsunami wave intensity; the time history of water levels were influenced by the different initial water level conditions; the analytical solution proposed by Chanson (2005) may be extended to wet-bed conditions (for initial water level < 0.36 tsunami bore height in our experimental set-up). Due to the limitations of experimental ranges in the laboratory, the validated numerical model can provide more results for wider experimental ranges for tsunami bore investigations. It was observed from numerical results that, tsunami bore height increases with the increase of reservoir water level; tsunami bore velocity decreases with the increased initial water level on the bed; as the initial water level on the bed gradually increases, the mean tsunami bore Froude number shows a downward trend.

The Co3O4 is a typical p-type metal oxide semiconductor (MOS) that attracted great attention for hydrogen detection. In this work, porous, urchin-like Co3O4 was synthesized using a hydrothermal method with the assistance of glucose and a subsequent calcination process. Urchin-like Co3O4 has a large specific surface area of 81.4 m2/g. The response value of urchin-like Co3O4 to 200 ppm hydrogen at 200 °C is 36.5 (Rg/Ra), while the low-detection limit is as low as 100 ppb. The obtained Co3O4 also exhibited good reproducibility, long-term stability, and selectivity towards various gases (e.g., ammonia, hydrogen, carbon monoxide, and methane). Porous, urchin-like Co3O4 is expected to become a potential candidate for low-concentration hydrogen-sensing materials with the above advantages.

The mental health crisis poses a major challenge to global sustainable development. In response, the United Nations has launched an ambitious plan to “reshape the environment that affects mental health”. Clean toilets are an important measure of civilization, yet it is unclear whether they are helping to alleviate the global mental health crisis. Therefore, using data from a large sample of rural Chinese households and introducing an instrumental variables approach based on the IV-Tobit model to address endogeneity, this study quantitatively discusses that clean latrines have a positive effect on the mental health of farm households. The results showed the following: (1) 89.8% of Chinese rural households had clean toilets, while the average farm household depression index was 12.568; and (2) clean toilets helped to improve the mental health of farmers, which means that the depression index of farmers with clean toilets decreased by 66.9% compared to farmers without clean toilets. The findings of this study can inform the development of policies to mitigate the global mental health crisis and contribute to the resilience of global development.

IntroductionThe macromolecular polysaccharide Inonotus obliquus polysaccharide (IOP) is composed of various monosaccharides, and it could modulate the composition and diversity of intestinal flora. However, its impact on the intestinal flora in rats of different genders remains unclear. Therefore, this study aims to investigate the structural changes of IOP and its effects on the intestinal flora after administration in male and female rats.MethodsIn this study, the molecular weight and purity of IOP were analyzed by high-performance gel permeation chromatography (HPGPC) and phenol sulfuric acid method, and NMR was used to confirm the chemical structure of IOP. Sex hormone [testosterone (T) and estradiol (E2)] levels and intestinal microbial changes were detected by enzyme-linked immunosorbent assay (ELISA) and 16S rRNA, respectively, after gavage of IOP (100 mg/kg) in male and female Sprague Dawley (SD) rats.ResultsHPGPC analysis showed that the average molecular weight (Mw) of IOP was 4,828 Da, and the total sugar content of the purified IOP was 96.2%, indicating that the polysaccharide is of high purity. NMR revealed that IOP is a linear macromolecule with an α-D-type glucose backbone. The results of ELISA and 16S rRNA showed that the IOP increased the abundance of beneficial bacteria, such as Clostridia_UCG-014 and Prevotellaceae_NK3B31, and reduced that of harmful bacteria, such as Colidextribacter and Desulfobacterota in the intestine of both male and female rats, and IOP changed the levels of sex hormones in male and female rats. Further analyses revealed that the increase in alpha diversity was higher in male than female rats. α diversity and β diversity revealed a significant difference in the composition of cecal microbiota between male and female rats in the control group, but IOP intake reduced this difference. Meanwhile, α analysis revealed a change in the composition of bacterial flora was more stable in male than female rats.ConclusionsThis study enhances our comprehension of the IOP structure and elucidates the alterations in intestinal flora following IOP administration in rats of varying genders. Nonetheless, further investigation is warranted to explore the specific underlying reasons for these discrepancies.

Background and objectives: There are concerns about the serological responses to Coronavirus disease 2019 (COVID-19) vaccines in inflammatory bowel disease (IBD) patients, particularly those receiving anti-TNF therapy. This study aimed to systematically evaluate the efficacy of COVID-19 vaccines in IBD patients receiving anti-TNF therapy. Methods: Electronic databases were searched to identify relevant studies. We calculated pooled seroconversion rate after COVID-19 vaccination and subgroup analysis for vaccine types and different treatments were performed. Additionally, we estimated pooled rate of T cell response, neutralization response, and breakthrough infections in this population. Results: 32 studies were included in the meta-analysis. IBD patients receiving anti-TNF therapy had relatively high overall seroconversion rate after complete vaccination, with no statistical difference in antibody responses associated with different drug treatments. The pooled positivity rate of T cell response was 0.85 in IBD patients receiving anti-TNF therapy. Compared with healthy controls, the positivity of neutralization assays was significantly lower in IBD patients receiving anti-TNF therapy. The pooled rate of breakthrough infections in IBD patients receiving anti-TNF therapy was 0.04. Conclusions: COVID-19 vaccines have shown good efficacy in IBD patients receiving anti-TNF therapy. However, IBD patients receiving anti-TNF have a relatively high rate of breakthrough infections and a low level of neutralization response.

Environmental exposure to hazardous materials causes enormous socioeconomic problems due to its deleterious impacts on human beings, agriculture and animal husbandry. As an important hazardous material, cadmium can promote uterine oxidative stress and inflammation, leading to reproductive toxicity. Antioxidants have been reported to attenuate the reproductive toxicity associated with cadmium exposure. In this study, we investigated the potential protective effect of procyanidin oligosaccharide B2 (PC-B2) and gut microbiota on uterine toxicity induced by cadmium exposure in rats. The results showed that the expression levels of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were reduced in utero. Proinflammatory cytokines (including tumor necrosis factor-α, interleukin-1β and interleukin-6), the NLRP3 inflammasome, Caspase-1 and pro-IL-1β were all involved in inflammatory-mediated uterine injury. PC-B2 prevented CdCl2-induced oxidative stress and inflammation in uterine tissue by increasing antioxidant enzymes and reducing proinflammatory cytokines. Additionally, PC-B2 significantly reduced cadmium deposition in the uterus, possibly through its significant increase in MT1, MT2, and MT3 mRNA expression. Interestingly, PC-B2 protected the uterus from CdCl2 damage by increasing the abundance of intestinal microbiota, promoting beneficial microbiota, and inhibiting harmful microbiota. This study provides novel mechanistic insights into the toxicity of environmental cadmium exposure and indicates that PC-B2 could be used in the prevention of cadmium exposure-induced uterine toxicity.

Improving the quality of wavefront shaping (WFS) is a major problem of anti-scattering optical information transmission in the perturbation environment. To tackle this issue, we propose a simple and robust method, named Point Guard algorithm (PGA), to manipulate the optical interference by encoding the digital micromirror device (DMD). The PGA method is inspired by the movement strategies of Point Guard (PG) in professional basketball association. Compared with the most popular method genetic algorithm (GA), the proposed PGA method has a stronger anti-perturbation capacity. In the experiment, the scattering medium consists of ground glass and polystyrene microspheres (PS) suspended in deionized water, and the movement of microspheres is used to cause a perturbation. It is found that PGA still has a better modulation quality when the suspension is too thick to see the ballistic light. PGA puts a new perspective in applications such as optogenetics and biomedical imaging in complex environment.

BackgroundAscending clinical evidence supports that electroacupuncture (EA) is effective in treating post-ischemic depression (PID), but little is known about how it works at the cellular level. Astrocytes are exquisitely sensitive to their extracellular environment, and under stressful conditions, they may experience aberrant structural remodeling that can potentially cause neuroplastic disturbances and contribute to subsequent changes in mood or behavior.ObjectivesThis study aimed to investigate the effect of EA on behavioral deficits associated with PID in mice and verify the hypothesis that astrocytic morphology may be involved in this impact.MethodsWe established a PID animal model induced by transient bilateral common carotid artery occlusion (BCCAO, 20 min) and chronic restraint stress (CRS, 21 days). EA treatment (GV20 + ST36) was performed for 3 weeks, from Monday to Friday each week. Depressive- and anxiety-like behaviors and sociability were evaluated using SPT, FST, EPM, and SIT. Immunohistochemistry combined with Sholl and cell morphological analysis was utilized to assess the process morphology of GFAP+ astrocytes in mood-related regions. The potential relationship between morphological changes in astrocytes and behavioral output was detected by correlation analysis.ResultsBehavioral assays demonstrated that EA treatment induced an overall reduction in behavioral deficits, as measured by the behavioral Z-score. Sholl and morphological analyses revealed that EA prevented the decline in cell complexity of astrocytes in the prefrontal cortex (PFC) and the CA1 region of the hippocampus, where astrocytes displayed evident deramification and atrophy of the branches. Eventually, the correlation analysis showed there was a relationship between behavioral emotionality and morphological changes.ConclusionOur findings imply that EA prevents both behavioral deficits and structural abnormalities in astrocytes in the PID model. The strong correlation between behavioral Z-scores and the observed morphological changes confirms the notion that the weakening of astrocytic processes may play a crucial role in depressive symptoms, and astrocytes could be a potential target of EA in the treatment of PID.

BackgroundLiver cancer is one of the major diseases threatening human life and health, and this study aims to explore new methods for treating liver cancer.MethodsA deep learning model for the efficacy of clinical herbal medicines for liver cancer was constructed based on NDCNN, combined with the natural evolutionary rules of a genetic algorithm to obtain the herbal compound for liver cancer treatment. We obtained differential genes between liver cancer tissues and normal tissues from the analysis of TCGA database, screened the active ingredients and corresponding targets of the herbal compound using the TCMSP database, mapped the intersection to obtain the potential targets of the herbal compound for liver cancer treatment in the Venny platform, constructed a PPI network, and conducted GO analysis and KEGG analysis on the targets of the herbal compound for liver cancer treatment. Finally, the key active ingredients and important targets were molecularly docked.ResultsThe accuracy of the NDCNN training set was 0.92, and the accuracy of the test set was 0.84. After combining with the genetic algorithm for 1,000 iterations, a set of Chinese herbal compound prescriptions was finally the output. A total of 86 targets of the herbal compound for liver cancer were obtained, mainly five core targets of IL-6, ESR1, JUN, IL1β, and MMP9. Among them, quercetin, kaempferol, and stigmasterol may be the key active ingredients in hepatocellular carcinoma, and the herbal compound may be participating in an inflammatory response and the immune regulation process by mediating the IL-17 signaling pathway, the TNF signaling pathway, and so on. The anticancer effects of the herbal compound may be mediated by the IL-17 signaling pathway, the TNF signaling pathway, and other signaling pathways involved in inflammatory response and immune regulation. Molecular docking showed that the three core target proteins produced stable binding to the two main active ingredients.ConclusionThe screening of effective herbal compounds for the clinical treatment of liver cancer based on NDCNN and genetic algorithms is a feasible approach and will provide ideas for the development of herbal medicines for the treatment of liver cancer and other cancers.

Evodia rutaecarpa (Evodia) is a Chinese herbal medicine with analgesic and anti-neurodegenerative properties. However, whether Evodia compounds can be applied for the comorbid pain of Alzheimer's disease (AD) and the underlying mechanisms remain unclear. Herein, 137 common targets of Evodia between AD and pain were predicted from drug and disease target databases. Subsequently, protein-protein interaction (PPI) network, protein function module construction, and bioinformatics analyses were used to analyze the potential relationship among targets, pathways, and diseases. Evodia could simultaneously treat AD comorbid pain through multi-target, multi-component, and multi-pathway mechanisms, and inflammation was an important common phenotype of AD and pain. The relationship between important transcription factors such as RELA, NF-κB1, SP1, STAT3, and JUN on IL-17, TNF, and MAPK signaling pathways might be potential mechanisms of Evodia. Additionally, 10 candidate compounds were predicted, and evodiamine might be the effective active ingredient of Evodia in treating AD or pain. In summary, this study provided a reference for subsequent research and a novel understanding and direction for the clinical use of evodiamine to treat AD patients with comorbid pain.

Cadmium (Cd) is a toxic element that can negatively affect both humans and animals. It enters the human and animal bodies through the respiratory and digestive tracts, following which it tends to accumulate in different organs, thereby seriously affecting human and animal health, as well as hampering social and economic development. Cd exposure can alter the composition of intestinal microbiota. In addition, it can damage the peripheral organs by causing the translocation of intestinal microbiota. However, the relationship between translocation-induced changes in the composition of microbiome in the blood and metabolic changes remains unclear. In the present study, we investigated the effects of Cd exposure on microbiota and serum metabolism in rats by omics analysis. The results demonstrated that Cd exposure disrupted the balance between the blood and intestinal flora in Sprague–Dawley (SD) rats, with a significant increase in gut microbiota (Clostridia_UCG_014, NK4A214_group) and blood microbiome (Corynebacterium, Muribaculaceae). However, Cd exposure caused the translocation of Corynebacterium and Muribaculaceae from the gut into the blood. In addition, Cd exposure was associated with the up-regulation of serum indoxyl sulfate, phenyl sulfate, and p-cresol sulfate; down-regulation of δ-tocopherol and L-glutamine; and changes in blood microbiome and metabolites. In conclusion, we identified novel metabolic biomarkers for Cd toxicity, which will also expand our understanding of the role of blood microbiome in Cd-induced injury.

Abstract Platinum‐based ordered alloy catalysts possess higher intrinsic activity in oxygen reduction reactions (ORR). High‐temperature annealing during ordered alloy formation frequently results in larger nanoparticles, and the strategy for obtaining ordered alloys at 600 °C is still undefined. Herein, an ordered Fe‐doped PtCo catalyst (O‐PtCoFe/C) with a size of sub‐4 nm was prepared at 600 °C derived from PtFe@CoO. CoO can generate oxygen vacancies by H2 reduction, lowering the atomic migration barrier and serving as a protective layer to inhibit nanoparticle migration. Experimental analyses showed the formation of O‐PtCoFe/C and electron‐rich Pt atoms due to Pt, Co, and Fe, which was advantageous for ORR performance. The mass activity of the prepared catalyst for ORR was 382.8 mA mgPt−1, which is 5.4 times greater than Pt/C. After 10000 potential cycles, the half‐wave potential was only negatively shifted by 10 mV. In PEMFC (proton exchange membrane fuel cells) tests, the O‐PtCoFe/C showed only 3 % decay after 3000 cycles, whereas the Pt/C showed a significant loss (18.4 %). This work provides an effective method for preparing ordered PtCo alloys for fuel cell cathode catalysts at 600 °C.

Summary: Polarity proteins regulate the proliferation and differentiation of neural progenitors to generate neurons during brain development through multiple signaling pathways. However, how cell polarity couples the signaling pathways remains unclear. Here, we show that coiled-coil domain-containing protein 85c (Ccdc85c) interacts with the polarity protein Par3 to regulate the proliferation of radial glial cells (RGCs) via phase separation coupled to percolation (PSCP). We find that the interaction with Ccdc85c relieves the intramolecular auto-inhibition of Par3, which leads to PSCP of Par3. Downregulation of Ccdc85c causes RGC differentiation. Importantly, the open conformation of Par3 facilitates the recruitment of the Notch regulator Numb to the Par3 condensates, which might prevent the attenuation of Notch activity to maintain RGC proliferation. Furthermore, ectopic activation of Notch signaling rescues RGC proliferation defects caused by the downregulation of Ccdc85c. These results suggest that Ccdc85c-mediated PSCP of Par3 regulates Notch signaling to control RGC proliferation during brain development.