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Implant-associated infection (IAI) has become an intractable challenge in clinic. The healing of IAI is a complex physiological process involving a series of spatiotemporal connected events. However, existing titanium-based implants in clinic suffer from poor antibacterial effect and single function. Herein, a versatile surface platform based on the presentation of sequential function is developed. Fabrication of titania nanotubes and poly-γ-glutamic acid (γ-PGA) achieves the efficient incorporation of silver ions (Ag+) and the pH-sensitive release in response to acidic bone infection microenvironment. The optimized PGA/Ag platform exhibits satisfactory biocompatibility and converts macrophages from pro-inflammatory M1 to pro-healing M2 phenotype during the subsequent healing stage, which creates a beneficial osteoimmune microenvironment and promotes angio/osteogenesis. Furthermore, the PGA/Ag platform mediates osteoblast/osteoclast coupling through inhibiting CCL3/CCR1 signaling. These biological effects synergistically improve osseointegration under bacterial infection in vivo, matching the healing process of IAI. Overall, the novel integrated PGA/Ag surface platform proposed in this study fulfills function cascades under pathological state and shows great potential in IAI therapy.

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Na superionic conductor (NASICON)-structured compounds demonstrate great application potential by their robust framework and compositional diversity. However, they are blamed for the mediocre energy density, and achieving both multielectron reaction and good cycling stability simultaneously is challenging. Herein, a novel heterogeneous Na4Fe3(PO4)2(P2O7)/Na2VTi(PO4)3 (NFPP/NVTP) material with stable multielectron reaction is constructed by spray drying technology. The mutual promotion effect of intergrowth structures effectively improves the purity and the crystallization of NFPP/NVTP during the fabrication process, which is beneficial to the high capacity and cycling stability. As a result, the optimized NFPP/NVTP demonstrates a high reversible capacity of 155.3 mAh g-1 at 20 mA g-1 and outstanding cycling stability with 82.9% capacity retention over 2500 cycles at 1 A g-1, which are much superior to those of NFPP and NVTP individually. Even in full cell configuration, the energy density remains high at ≈380 Wh kg-1 based on the cathode mass. The high capacity of NFPP/NVTP is also attributed to the successive reduction/oxidation mechanism involving the introduction of Ti3+ and interfacial charge redistribution effect between the heterogeneous phases, which greatly improve the electronic and ionic conductivity. Moreover, high reversible structural evolution during the multisodium storage process further guarantees excellent cycling stability.

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Pollination is one of the important ecosystem services related to sustainable development of human society. However, the population diversity and abundance of wild bees, important pollinators, have been significantly reduced by climate change, agricultural intensification, and landscape transformation. Re-establishment of pollinator habitat by planting nectar-producing plants is an important way to maintain pollination service. In this study, we investigated the status of wild bees and the traits of flowering plants in 22 apple orchards during flowering stage in Changping District, Beijing in 2019. We analyzed the response of wild bee diversity to the flowering plant richness, flower color richness, inflorescence type richness, flowering plant coverage, herbaceous layer coverage and different flower color coverage in apple orchards, aiming to provide guidance for the selection of nectar-producing plants to establish the habitat of wild bees. A total of 3517 wild bees were captured during the apple flowering season, representing 49 species, 13 genera, and 5 families. We identified 21 flowering plants species that shared a similar flo-wering period with apple, exhibiting a range of 5 colors and 9 inflorescence types. The Shannon diversity index, evenness index, and social bee richness of wild bee community were positively correlated with flowering plant richness. The total wild bee community richness, social bee richness, underground nesting bee richness were positively correlated with the richness of flowering plant color, but Halictidae bee abundance was negatively correlated with the richness of flowering plant color. The Shannon diversity index and evenness index of wild bee community were positively correlated with the richness of inflorescence types. Megachilidae bee richness was negative correlated with the white flower coverage. Megachilidae bee richness, social bee abundance, and ground nesting bee richness were positively correlated with the purple flower coverage. There was no significant correlation between wild bees and flowering plant richness, flower color richness, inflorescence type richness, flowering plant coverage, herbaceous layer coverage and different flower color coverage in other communities of different families, lifestyles and nesting types. Maintaining diverse ground flowering plants with various traits in orchards is important to improve the diversity of wild bees. In particular, increasing the coverage of purple flower during apple flowering period is helpful to promote the diversity of Megachilidae bee, social bees, and ground nesting bees.

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We analyzed age structure and dynamics, spatial distribution patterns, and reproductive capabilities of four Rosa persica populations in Xinjiang, to evaluate the survival status of the species and explore the reasons behind its endangerment. The results showed that the populations had fewer individuals in the youngest (Ⅰ) and oldest (Ⅵ-Ⅷ) age classes, with a predominance of middle-aged individuals, resulting in an irregular pyramid-shaped distribution, described as "high in the middle, low on both sides". The populations were generally growing, but were susceptible to external environmental disturbances (Vpi'＞0, Pmax＞0). The mortality rate (qx) and vanish rate (Kx) peaked at age Ⅴ, leading to a sharp decline in plant abundance. The life expectancy (ex) decreased progressively with the increases of age class, reaching its lowest at age Ⅷ, which indicated minimal vitality at this stage. A time sequence analysis predicted a future dominance of individuals at age Ⅴ-Ⅷ, suggesting an aging trend. Spatially, the four populations were predominantly clumped, with the intensity of clumping ranked from highest to lowest as P4, P3, P1, and P2. P3 and P4 exhibited better reproductive capabilities than P1 and P2. There was a significant positive correlation between hundred-fruit weight and plant height and crown width, and between total seed number and crown width and hundred-fruit weight.

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PURPOSE: This study aims to assess the diagnostic efficacy of Korean Thyroid imaging reporting and data system (K-TIRADS), S-Detect software and contrast-enhanced ultrasound (CEUS) when employed individually, as well as their combined application, for the evaluation of thyroid nodules, with the objective of identifying the optimal method for diagnosing thyroid nodules. METHODS: Two hundred and sixty eight cases pathologically proven of thyroid nodules were retrospectively enrolled. Each nodule was classified according to K-TIRADS. S-Detect software was utilized for intelligent analysis. CEUS was employed to acquire contrast-enhanced features. RESULTS: The area under curve (AUC) values for diagnosing benign and malignant thyroid nodules using K-TIRADS alone, S-Detect software alone, CEUS alone, the combined application of K-TIRADS and CEUS, the combined application of S-Detect software and CEUS were 0.668, 0.668, 0.719, 0.741, and 0.759, respectively (p < 0.001). The sensitivity rate of S-Detect software was 89.9% (p < 0.001). It was the highest of the five diagnostic methods above. CONCLUSION: The utilization of S-Detect software can be served as a powerful tool for early screening. Notably, the combined utilization of S-Detect software with CEUS demonstrates superior diagnostic performance compared to employing K-TIRADS, S-Detect software, CEUS used individually, as well as the combined application of K-TIRADS with CEUS.

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Objective: Hypertension (HTN) is a prevalent global health concern. From the standpoint of preventive and personalized medicine (PPPM/3PM), early detection of HTN offers a crucial opportunity for targeted prevention and personalized treatment. This study aimed to evaluate the association between the weight-adjusted waist index (WWI) and HTN risk. Methods: A case-control study using data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 was conducted. Logistic regression models assessed the association between WWI and HTN. Subgroup analyses explored differences in age, sex, ethnicity, and diabetes status. Restricted cubic spline (RCS) analyses examined potential nonlinear relationships. Results: A total of 32,116 participants, with an average age of 49.28 ± 17.56 years, were included in the study. A significant positive association between WWI and the risk of HTN was identified (odds ratio [OR], 2.49; 95% CI, 2.39-2.59; P < 0.001). When WWI was categorized into quartiles (Q1-Q4), the highest quartile (Q4) exhibited a stronger association compared to Q1 (OR, 2.94; 95% CI, 2.65-3.27; P < 0.001). Subgroup analyses indicated that WWI was a risk factor for HTN across different populations, although variations in the magnitude of effect were observed. Furthermore, the findings from the RCS elucidated a nonlinear positive correlation between WWI and HTN. Conclusion: WWI is independently associated with HTN risk, highlighting its potential as a risk assessment tool in clinical practice. Incorporating WWI into early detection strategies enhances targeted prevention and personalized management of HTN. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00375-3.

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Recent years have witnessed the great success of the applications of graph convolutional networks (GCNs) in various scenarios. However, due to the challenging over-smoothing and over-squashing problems, the ability of GCNs to model information from long-distance nodes has been largely limited. One solution is to aggregate features from different hops of neighborhoods with a linear combination of them followed by a shallow feature transformation. However, we demonstrate that those methods can only achieve a tradeoff between tackling those two problems. To this end, in this article, we design a simple yet effective graph convolution (GC), named maximization-based GC (MGC). Instead of using the linear combination, MGC applies an elementwise maximizing operation for exploiting all possible powers of the normalized adjacent matrix to construct a GC operation. As evidenced by theoretical and empirical analysis, MGC can effectively handle the above two problems. Besides, an efficient approximated model with a linear complexity is developed to extend MGC for large-scale graph learning. To demonstrate the effectiveness, scalability, and efficiency of our models, extensive experiments have been conducted on various benchmark datasets. In particular, our models achieve competitive performance with lower complexity, even on large graphs with more than 100M nodes. Our code is available at https://github.com/SmilesDZgk/MGC.

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Recently we have shown that protein disulfide isomerase (PDI or PDIA1) is involved in mediating chemically-induced, glutathione (GSH) depletion-associated ferroptotic cell death through NOS activation (dimerization) and NO accumulation. The present study aims to determine the role of PDI in mediating chemically-induced hepatocyte injury in vitro and in vivo and whether PDI inhibitors can effectively protect against chemically-induced hepatocyte injury. We show that during the development of erastin-induced ferroptotic cell death, accumulation of cellular NO, ROS and lipid-ROS follows a sequential order, i.e., cellular NO accumulation first, followed by accumulation of cellular ROS, and lastly cellular lipid-ROS. Cellular NO, ROS and lipid-ROS each play a crucial role in mediating erastin-induced ferroptosis in cultured hepatocytes. In addition, it is shown that PDI is an important upstream mediator of erastin-induced ferroptosis through PDI-mediated conversion of NOS monomer to its dimer, which then leads to accumulation of cellular NO, ROS and lipid-ROS, and ultimately ferroptotic cell death. Genetic manipulation of PDI expression or pharmacological inhibition of PDI function each can effectively abrogate erastin-induced ferroptosis. Lastly, evidence is presented to show that PDI is also involved in mediating acetaminophen-induced liver injury in vivo using both wild-type C57BL/6J mice and hepatocyte-specific PDI conditional knockout (PDIfl/fl Alb-cre) mice. Together, our work demonstrates that PDI is an important upstream mediator of chemically-induced, GSH depletion-associated hepatocyte ferroptosis, and inhibition of PDI can effectively prevent this injury.

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Rigid solenoid coils have long been indispensable in modern intelligent devices. However, their sparse structure and challenging preparation of flexible coils for soft robots impose limitations. Here, a transformable 3D curved high-density liquid metal coil (HD-LMC) is introduced that surpasses the structural density level of enameled wire. The fabrication technique employed for high-density channels in elastomers is universally applicable. Such HD-LMCs demonstrated excellent performance in pressure, temperature, non-contact distance sensors, and near-field communication. Soft electromagnetic actuators thus achieved significantly improved the electromagnetic force and power density. Moreover, precise control of swinging tail motion enables a bionic pufferfish to swim. Finally, HD-LMC is further utilized to successfully implement a soft rotary robot with integrated sensing and actuation capabilities. This groundbreaking research provides a theoretical and experimental basis for expanding the applications of liquid metal-based multi-dimensional complex flexible electronics and is expected to be widely used in liquid metal-integrated robotic systems.

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Epidemiological studies have revealed an inverse relationship between the incidence of Alzheimer's disease (AD) and various cancers, including colorectal cancer (CRC). We aimed to determine whether the incidence of CRC is reduced in AD-like mice and whether gut microbiota confers resistance to tumorigenesis through inducing inflammatory tolerance using 16S ribosomal RNA gene sequencing and fecal microbiota transplantation (FMT). AD-like mice experienced a significantly decreased incidence of CRC tumorigenesis induced by azoxymethane-dextran sodium sulfate as evidenced by suppressed intestinal inflammation compared with control mice. However, FMT from age-matched control mice reversed the inhibitory effects on the tumorigenesis of CRC and inflammatory response in AD-like mice. The key bacterial genera in gut microbiota, including Prevotella, were increased in both the AD-like mice and in patients with amnestic mild cognitive impairment (aMCI) but were decreased in patients with CRC. Pretreatment with low-dose Prevotella-derived lipopolysaccharides (LPS) induced inflammatory tolerance both in vivo and in vitro and inhibited CRC tumorigenesis in mice. Imbalanced gut microbiota increased intestinal barrier permeability, which facilitated LPS absorption from the gut into the blood, causing cognitive decline in AD-like mice and patients with aMCI. These data reveal that intestinal Prevotella-derived LPS exerts a resistant effect to CRC tumorigenesis via inducing inflammatory tolerance in the presence of AD. These findings provide biological evidence demonstrating the inverse relationship between the incidence of AD and CRC.

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Reperfusion injury represents a significant impediment to recovery after recanalization in an ischemic stroke and can be alleviated by neuroprotectants. However, inadequate drug delivery to ischemic lesions impairs the therapeutic effects of neuroprotectants. To address this issue, an ischemic microenvironment-targeted bioinspired lipoprotein system encapsulating lipoic acid (LA@PHDL) is herein designed to sequentially penetrate ischemic lesions and be readily taken up by neurons and microglia. In transient middle cerebral artery occlusion (tMCAO) mouse models, LA@PHDL accumulates rapidly and preferentially in the ischemic brain, with a 2.29-fold higher than the nontargeted nanoplatform in the early stage. Furthermore, LA@PHDL effectively restores neurological function, reduces infarct volume to 17.70%, prevents brain cell necrosis and apoptosis, and attenuates inflammation in tMCAO mouse models. This design presents new opportunities for delivering neuroprotectants to cerebral ischemic lesions to improve the outcome of an ischemic stroke.

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Soybean rust (SBR), caused by an obligate biotrophic pathogen Phakopsora pachyrhizi, is a devastating disease of soybean worldwide. However, the mechanisms underlying plant invasion by P. pachyrhizi are poorly understood, which hinders the development of effective control strategies for SBR. Here we performed detailed histological characterization on the infection cycle of P. pachyrhizi in soybean and conducted a high-resolution transcriptional dissection of P. pachyrhizi during infection. This revealed P. pachyrhizi infection leads to significant changes in gene expression with 10 co-expressed gene modules, representing dramatic transcriptional shifts in metabolism and signal transduction during different stages throughout the infection cycle. Numerous genes encoding secreted protein are biphasic expressed, and are capable of inhibiting programmed cell death triggered by microbial effectors. Notably, three co-expressed P. pachyrhizi apoplastic effectors (PpAE1, PpAE2, and PpAE3) were found to suppress plant immune responses and were essential for P. pachyrhizi infection. Double-stranded RNA coupled with nanomaterials significantly inhibited SBR infection by targeting PpAE1, PpAE2, and PpAE3, and provided long-lasting protection to soybean against P. pachyrhizi. Together, this study revealed prominent changes in gene expression associated with SBR and identified P. pachyrhizi virulence effectors as promising targets of RNA interference-based soybean protection strategy against SBR.

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In this editorial, we delved into the article titled "Cellular preconditioning and mesenchymal stem cell ferroptosis." This groundbreaking study underscores a pivotal discovery: Ferroptosis, a type of programmed cell death, drastically reduces the viability of donor mesenchymal stem cells (MSCs) after engraftment, thereby undermining the therapeutic value of cell-based therapies. Furthermore, the article proposes that by manipulating ferroptosis mechanisms through preconditioning, we can potentially enhance the survival rate and functionality of MSCs, ultimately amplifying their therapeutic potential. Given the crucial role ferroptosis plays in shaping the therapeutic outcomes of MSCs, we deem it imperative to further investigate the intricate interplay between programmed cell death and the therapeutic effectiveness of MSCs.

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Introduction: Grape is of high economic value. Colletotrichum viniferum, a pathogen causing grape ripe rot and leaf spot, threatens grape production and quality. Methods: This study investigates the interplay between C. viniferum by Cytological study and transcriptome sequencing. Results: Different grapevine germplasms, V. vinifera cv. Thompson Seedless (TS), V. labrusca accession Beaumont (B) and V. piasezkii Liuba-8 (LB-8) were classified as highly sensitive, moderate resistant and resistant to C. viniferum, respectively. Cytological study analysis reveals distinct differences between susceptible and resistant grapes post-inoculation, including faster pathogen development, longer germination tubes, normal appressoria of C. viniferum and absence of white secretions in the susceptible host grapevine. To understand the pathogenic mechanisms of C. viniferum, transcriptome sequencing was performed on the susceptible grapevine "TS" identifying 236 differentially expressed C. viniferum genes. These included 56 effectors, 36 carbohydrate genes, 5 P450 genes, and 10 genes involved in secondary metabolism. Fungal effectors are known as pivotal pathogenic factors that modulate plant immunity and affect disease development. Agrobacterium-mediated transient transformation in Nicotiana benthamiana screened 10 effectors (CvA13877, CvA01508, CvA05621, CvA00229, CvA07043, CvA05569, CvA12648, CvA02698, CvA14071 and CvA10999) that inhibited INF1 (infestans 1, P. infestans PAMP elicitor) induced cell death and 2 effectors (CvA02641 and CvA11478) that induced cell death. Additionally, transcriptome analysis of "TS" in response to C. viniferum identified differentially expressed grape genes related to plant hormone signaling (TGA, PR1, ETR, and ERF1/2), resveratrol biosynthesis genes (STS), phenylpropanoid biosynthesis genes (PAL and COMT), photosynthetic antenna proteins (Lhca and Lhcb), transcription factors (WRKY, NAC, MYB, ERF, GATA, bHLH and SBP), ROS (reactive oxygen species) clearance genes (CAT, GSH, POD and SOD), and disease-related genes (LRR, RPS2 and GST). Discussion: This study highlights the potential functional diversity of C. viniferum effectors. Our findings lay a foundation for further research of infection mechanisms in Colletotrichum and identification of disease response targets in grape.

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AIMS: This study aimed to investigate the impact of different estimated glomerular filtration rate (eGFR) values like cystatin C-based eGFR (eGFRcys), creatinine-based eGFR (eGFRcr), and their difference (eGFRdiff; eGFRcys -eGFRcr), on the incidence of heart failure (HF) in patients with type 2 diabetes(T2D). METHODS: Being a prospective cohort study, it included 7,967 patients with T2D who underwent serum creatinine and cystatin C tests as part of the Kailuan Group's 6th annual health examination (2016). Subsequently, eGFRcys, eGFRcr, and eGFRdiff were calculated. Patients were categorized into three groups: negative (<-15 mL/min/1.73 m2), midrange (-15 to 15 mL/min/1.73 m2), and positive (> 15 mL/min/1.73 m2) eGFRdiff groups, respectively. Furthermore, the relationship between the various eGFR measurements and new-onset HF were studied using Cox proportional hazards regression, and the potential improvement in predictive capability was evaluated by adding these eGFR metrics to established HF risk models. RESULTS: Among 7967 participants with mean age of 60.51 years, there were 20.92% women and 79.08% men. At baseline, eGFRcys and eGFRcr values differed by more than 15 mL/min/1.73m2 in 41.3% of participants. During a median follow-up period of 3.76 years, there were 172 (2.16%) new HF cases and 517 (6.49%) all-cause deaths. The cumulative incidence of HF in the midrange, negative, and positive eGFRdiff groups was 1.74%, 4.10%, and 0.61%, respectively (p < 0.001). In multivariable adjusted models, participants in the negative eGFRdiff group had higher risk of HF compared with the midrange eGFRdiff group (HR, 2.15; 95% CI, 1.57-2.94). Conversely, participants in the positive eGFRdiff group had lower risk for HF (HR, 0.40; 95% CI, 0.17-0.93). And each 15 mL/min/ 1.73 m2 higher eGFRdiff was associated with 34% (HR, 0.66; 95% CI, 0.58 - 0.47)lower risk of incident HF. The predictive capacity for HF risk in diabetic individuals was enhanced by adding eGFRcys or eGFRdiff to established HF risk models, with eGFRcys showing more significant additional predictive value. CONCLUSION: These findings suggest that large differences between eGFRcys and eGFRcr were common in community-based population with T2D. Different eGFR metrics can independently predict HF incidence in patients with T2D. Additionally, metrics like eGFRcys and eGFRdiff provide significant predictive value for HF risks beyond traditional risk factors, with eGFRcys showing more pronounced benefits in such cases.

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INTRODUCTION: Acute lung injury (ALI) as one kind of acute pulmonary inflammatory disorder, manifests primarily as damage to alveolar epithelial cells and microvascular endothelial cells. Activation of the complement system is a common pathological mechanism in ALI induced by diverse factors, with the complement alternative pathway assuming a pivotal role. Baicalin, a flavonoid derived from the root of Scutellaria baicalensis Georgi, exhibits noteworthy biological activities. The present study attempted the interventional effects and underlying mechanisms of baicalin in microangiopathy in ALI induced by complement alternative pathway activation. METHODS: Activation of the complement alternative pathway by cobra venom factor (CVF). HMEC cells were pretreated with baicalin and then exposed to complement activation products. The expression of inflammatory mediators was detected by ELISA, and the intranuclear transcriptional activity of NF-κB was assessed by a dual fluorescent kinase reporter gene assay kit. Before establishing the ALI mouse model, baicalin or PDTC was gavaged for 7 d. CVF was injected into the tail vein to establish the ALI model. The levels of inflammatory mediators in BALF and serum were determined by ELISA. HE staining and immunohistochemistry evaluated pathological changes, complement activation product deposition, and NF-κB p65 phosphorylation in lung tissue. RESULTS: Baicalin reduced complement alternative activation product-induced expression of HMEC cells adhesion molecules (ICAM-1, VCAM-1, E-selectin) and cytokines (IL-6, TNF-α) as well as upregulation of NF-κB intranuclear transcriptional activity. Baicalin intervention reduced the number of inflammatory cells and protein content in the BALF and decreased the levels of IL-6, TNF-α, and ICAM-1 in serum and IL-6, TNF-α, ICAM-1, and P-selectin in BLAF. In addition, baicalin attenuated inflammatory cell infiltration in the lung of ALI mice and reduced the deposition of complement activation products (C5a, C5b-9) and phosphorylation of NF-κB p65 in lung tissue. CONCLUSION: Baicalin relieves complement alternative pathway activation-induced lung inflammation by inhibition of NF-κB pathway, delaying the progression of ALI.

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Cognitive impairment is a core symptom of schizophrenia (SZ), with GABAergic dysfunction in the brain potentially serving as a critical pathological mechanism underlying this condition. Intracortical inhibition (ICI), which includes short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI), can be used to assess the inhibitory function of cortical GABAergic neurons. The aim of this study was to investigate the relationship between ICI and cognitive function, as well as psychopathological symptoms, in SZ patients. We recruited 130 SZ patients and 105 healthy controls (HCs). All subjects underwent paired-pulse transcranial magnetic stimulation (ppTMS) measurements, which included resting motor threshold (RMT), SICI and LICI. The cognitive function of all subjects was assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB). The psychopathological symptoms of the SZ group were assessed using the Positive and Negative Syndrome Scale (PANSS). We examined group differences in MCCB scores, RMT, SICI, and LICI. Within the SZ group, we assessed the relationship between ICI and cognitive function, as well as psychopathological symptoms. Two-way ANOVA, Mann-Whitney U test, Receiver operating characteristic (ROC) curves, and partial Spearman correlation analysis were performed. The SZ group showed a worse cognitive score in all 6 cognitive dimensions of the MCCB compared to the HC group (all p < 0.05). The SZ group had lower degree of SICI and LICI compared to the HC group (both p < 0.05). ROC curves analysis showed that SICI and LICI all displayed good performance in differentiating SZ patients and HCs (both p < 0.05), and SICI exhibited a better performance, yielding an area under the curve (AUC) of 0.856 (95% CI 0.807-0.904). Furthermore, in the SZ group, SICI demonstrated a significant negative correlation with PANSS positive score, negative score, general psychopathology score, and total score (all pBonferroni < 0.05), and LICI demonstrated a significant negative correlation with PANSS positive score, general psychopathology score and total score (all pBonferroni < 0.05). Additionally, in the SZ group, SICI demonstrated a significant positive correlation with speed of processing score, working memory score, verbal learning score, visual learning score, and reasoning and problem-solving score of the MCCB (all pBonferroni < 0.05), while LICI was only weakly positive correlated with speed of processing score of the MCCB (r = 0.247, p = 0.005, pBonferroni = 0.03). Our results demonstrate that the reduction of ICI could serve as a trait-dependent in-vivo biomarker of GABAergic deficits for SZ and related cognitive impairments.

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Grassland caterpillars (Lepidoptera: Lymantriinae: Gynaephora) are the most damaging pests to alpine meadows in the Qinghai-Tibetan Plateau (QTP). Here, we conducted extensive sampling from 39 geographic populations covering almost the entire distribution of the eight QTP Gynaephora (Hübner) species to investigate phylogeographic patterns and speciation based on two mitochondrial genes (COI and ND5). A total of 40 haplotypes were detected in the 39 populations, with >70% of all haplotypes not shared between populations. The monophyletic QTP Gynaephora migrated from non-QTP regions during the Pliocene, corresponding to the uplift of the QTP, suggesting a mode of transport into the QTP. Among the eight QTP Gynaephora species described by morphological characteristics, two species (G. alpherakii and G. menyuanensis) were recovered as monophyletic groups (Clades B and C), while the remaining six formed two monophyletic clades: Clade A (G. qinghaiensis, G. jiuzhiensis, and G. qumalaiensis) and Clade D (G. aureata, G. ruoergensis, and G. minora). These results suggested that the number of the QTP Gynaephora species may be overestimated and further studies based on both morphological and nuclear gene data are needed. Genetic differentiation and speciation of the QTP Gynaephora were likely driven by the QTP uplifts and associated climate fluctuations during the Pleistocene, indicated by divergence time estimation, suggesting that isolation and subsequent divergence was the dominant mode of speciation. The Sanjiangyuan region (i.e., Clade A, characterized by high genetic diversity) may have been a glacial refugium of the QTP Gynaephora, as supported by analyses of gene flow and biogeography. High levels of genetic diversity were found in QTP Gynaephora, without population expansion, which may explain the high-altitude adaptation and outbreaks of grassland caterpillars in alpine meadows of the QTP. This study provides the largest phylogeographic analysis of QTP Gynaephora and improves our understanding of the diversity and speciation of QTP insects.

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BACKGROUND: This study assessed the global trends and burden of severe chest injury, including rib fractures, lung contusions, and heart injuries from 1990 to 2019. Herein, we predicted the burden patterns and temporal trends of severe chest injuries to provide epidemiological evidence globally and in China. METHODS: In our analysis, the age-standardized incidence rate (ASIR), prevalence rate (ASPR), and years lived with disability rate (ASYR) of severe chest injury were analyzed by gender, age, sociodemographic index, and geographical region between 1990 and 2019 using data from the Global Burden of Disease study 2019. Trends were depicted by calculating the estimated annual percentage changes (EAPCs). The impact of age, period, and cohort factors was assessed using an Age-Period-Cohort model. Autoregressive integrated moving average (ARIMA) model was employed to predict severe chest injury trends from 2020 to 2050. RESULTS: In 2019, the global number of severe chest injury cases reached 7.95 million, with the highest incidence rate observed in Central Europe (209.61). Afghanistan had the highest ASIRs at 277.52, while North Korea had the lowest ASIRs at 41.02. From 1990 to 2019, the Syrian Arab Republic saw significant increases in ASIR, ASPR, and ASYR, with EAPCs of 10.4%, 9.31%, and 10.3%, respectively. Burundi experienced a decrease in ASIR with an EAPC of - 6.85% (95% confidence interval [CI] - 11.11, - 2.37), while Liberia's ASPR and ASYR declined with EAPCs of - 3.22% (95% CI - 4.73, - 1.69) and - 5.67% (95% CI - 8.00, - 3.28), respectively. Falls and road injuries remained the most common causes. The relative risk of severe chest injury by age, period, and cohort demonstrated a complex effect globally and in China. The ARIMA model forecasted a steady increase in global numbers from 2020 to 2050, while in China, it forecasted an increase in incidence, a decrease in ASIR and ASYR, and an increase in ASPR. CONCLUSIONS: This study provides a groundbreaking analysis of global severe chest injury, shedding light on its measures and impact. These findings highlight the need for timely, specialized care and addressing regional disparities to mitigate the severe chest injury burden.

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