Monoexponential and advanced diffusion-weighted imaging for hepatic fibrosis staging based on high inter-examiner reliability.

OBJECTIVES: To determine the diagnostic efficiencies of multiple diffusion-weighted imaging (DWI) techniques for hepatic fibrosis (HF) staging under the premise of high inter-examiner reliability. METHODS: Participants with biopsy-confirmed HF were recruited and divided into the early HF (EHF) and advanced HF (AHF) groups; healthy volunteers (HVs) served as controls. Two examiners analyzed intravoxel incoherent motion (IVIM) using the IVIM-DWI and diffusion kurtosis imaging (DKI) models. Intravoxel incoherent motion-DWI, DKI, and diffusion tensor imaging parameters with intraclass correlation coefficients (ICCs) of ≥0.6 were used to create regression models: HVs vs. EHF and EHF vs. AHF. RESULTS: We enrolled 48 HVs, 59 EHF patients, and 38 AHF patients. Mean, radial, and axial kurtosis; fractional anisotropy; mean, radial, and axial diffusivity; and α exhibited excellent reliability (ICCs: 0.80-0.98). Fractional anisotropy of kurtosis, f, and apparent diffusion coefficient showed good reliability (ICCs: 0.69-0.92). The real (0.58-0.67), pseudo- (0.27-0.76), and distributed diffusion coefficients (0.58-0.67) showed low reliability. In the HVs versus (vs.) EHF model, α (p=0.008) and ADC (p=0.011) presented statistical differences (area under curve [AUC]: 0.710). In the EHF vs. AHF model, α (p=0.04) and distributed diffusion coefficient (p=0.02) presented significant differences (AUC: 0.758). CONCLUSION: Under the premise of high inter-examiner reliability, DWI and IVIM-derived stretched-exponential model parameters may help stage HF.

Serotonergic transmission plays differentiated roles in the rapid and sustained antidepressant-like effects of ketamine.

BACKGROUND AND PURPOSE: The emerging antidepressant effects of ketamine have inspired tremendous interest in its underlying neurobiological mechanisms, although the involvement of 5-HT in the antidepressant effects of ketamine remains unclear. EXPERIMENTAL APPROACH: The chronic restraint stress procedure was performed to induce depression-like behaviours in mice. OFT, FST, TST, and NSFT tests were used to evaluate the antidepressant-like effects of ketamine. Tph2 knockout or depletion of 5-HT by PCPA and 5,7-DHT were used to manipulate the brain 5-HT system. ELISA and fibre photometry recordings were used to measure extracellular 5-HT levels in the brain. KEY RESULTS: 60 min after injection, ketamine (10 mg·kg-1, i.p.) produced rapid antidepressant-like effects and increased brain 5-HT levels. After 24 h, ketamine significantly reduced immobility time in TST and FST tests and increased brain 5-HT levels, as measured by ELISA and fibre photometry recordings. The sustained (24 h) but not rapid (60 min) antidepressant-like effects of ketamine were abrogated by PCPA and 5,7-DHT, or by Tph2 knockout. Importantly, NBQX (10 mg·kg-1, i.p.), an AMPA receptor antagonist, significantly inhibited the effect of ketamine on brain 5-HT levels and abolished the sustained antidepressant-like effects of ketamine in naïve or CRS-treated mice. CONCLUSION AND IMPLICATIONS: This study confirms the requirement of serotonergic neurotransmission for the sustained antidepressant-like effects of ketamine, which appears to involve AMPA receptors, and provides avenues to search for antidepressant pharmacological targets.

Quantifying species biases among multidata sources on illegal wildlife trade and its implications for conservation.

Unsustainable wildlife consumption and illegal wildlife trade (IWT) threaten biodiversity worldwide. Although publicly accessible data sets are increasingly used to generate insights into IWT, little is known about their potential bias. We compared three typical and temporally corresponding data sets (4204 court verdicts, 926 seizure news reports, and 219 bird market surveys) on traded birds native to China and evaluated their possible species biases. Specifically, we evaluated bias and completeness of sampling for species richness, phylogeny, conservation status, spatial distribution, and life-history characteristics among the three data sets when determining patterns of illegal trade. Court verdicts contained the largest species richness. In bird market surveys and seizure news reports, phylogenetic clustering was greater than that in court verdicts, where songbird species (i.e., Passeriformes) were detected in higher proportions in market surveys. The seizure news data set contained the highest proportion of species of high conservation priority but the lowest species coverage. Across the country, all data sets consistently reported relatively high species richness in south and southwest regions, but markets revealed a northern geographic bias. The species composition in court verdicts and markets also exhibited distinct geographical patterns. There was significant ecological trait bias when we modeled whether a bird species is traded in the market. Our regression model suggested that species with small body masses, large geographical ranges, and a preference for anthropogenic habitats and those that are not nationally protected were more likely to be traded illegally. The species biases we found emphasize the need to know the constraints of each data set so that they can optimally inform strategies to combat IWT.

Cuantificación del sesgo por especies entre fuentes de datos múltiples para el mercado ilegal de fauna y lo que implica para la conservación Resumen El consumo insostenible y el comercio ilegal de fauna y flora silvestres amenazan la biodiversidad en todo el mundo. Aunque los conjuntos de datos de acceso público se utilizan cada vez más para obtener información sobre el mercado ilegal de especies silvestres, se sabe poco sobre su posible sesgo. Comparamos tres conjuntos de datos típicos con correspondencia temporal (4,204 sentencias judiciales, 926 informes de noticias sobre incautaciones y 219 encuestas sobre mercados de aves) de aves autóctonas de China objeto de comercio y evaluamos sus posibles sesgos por especie. En concreto, evaluamos el sesgo y la exhaustividad del muestreo de la riqueza de especies, la filogenia, el estado de conservación, la distribución espacial y las características del ciclo vital entre los tres conjuntos de datos a la hora de determinar los patrones del mercado ilegal. Las sentencias judiciales contenían la mayor riqueza de especies. En los estudios de mercado de aves y en los informes de noticias sobre incautaciones, la agrupación filogenética fue mayor que en las sentencias judiciales, donde las especies de aves canoras (Passeriformes) se detectaron en mayor proporción en los estudios de mercado. El conjunto de datos de noticias sobre decomisos contenía la mayor proporción de especies de alta prioridad para la conservación, pero la menor cobertura de especies. En todo el país, todos los conjuntos de datos informaron sistemáticamente de una riqueza de especies relativamente alta en las regiones sur y suroeste, pero los mercados revelaron un sesgo geográfico septentrional. La composición por especies en los veredictos judiciales y en los mercados también mostró patrones geográficos distintos. Hubo un sesgo significativo de rasgos ecológicos cuando modelamos si una especie de ave se comercializa en el mercado. Nuestro modelo de regresión sugería que las especies con masas corporales pequeñas, grandes áreas de distribución geográfica y preferencia por los hábitats antropogénicos y las especies que no están protegidas a nivel nacional tenían más probabilidades de ser objeto de comercio ilegal. Los sesgos de las especies que hallamos resaltan la necesidad de conocer las limitaciones de cada conjunto de datos para poder informar de manera óptima las estrategias de lucha contra el comercio ilegal de especies silvestres.

Adipose-Derived Stem-Cell-Membrane-Coated PLGA-PEI Nanoparticles Promote Wound Healing via Efficient Delivery of miR-21.

miRNAs have been shown to be involved in the regulation of a variety of physiological and pathological processes, but their use in the treatment of diseases is still limited due to their instability. Biomimetic nanomaterials combine nanomaterials with cellular components that are readily modifiable and biocompatible, making them an emerging miRNA delivery vehicle. In this study, adipose-derived MSC membranes were wrapped around PLGA-PEI loaded with miR-21 through co-extrusion and later transplanted into C57BL/6 mice wounds. The wound-healing rate, epithelialization, angiogenesis, and collagen deposition were assessed after treatment and corroborated in vitro. Our study demonstrated that m/NP/miR-21 can promote wound healing in terms of epithelialization, dermal reconstruction, and neovascularization, and it can regulate the corresponding functions of keratinocytes, fibroblasts, and vascular endothelial cells. m/NP/miR-21 can inhibit the expression of PTEN, a gene downstream of miR-21, and increase the phosphorylation activation of AKT, which can then regulate the functions of fibroblasts. In conclusion, this provides a new approach to therapy for skin wounds using microRNA transporters and biomimetic nanoparticles.

Equol exerts anti-tumor effects on choriocarcinoma cells by promoting TRIM21-mediated ubiquitination of ANXA2.

Choriocarcinoma is a malignant cancer that belongs to gestational trophoblastic neoplasia (GTN). Herein, serum metabolomic analysis was performed on 29 GTN patients and 30 healthy individuals to characterize the metabolic variations during GTN progression. Ultimately 24 differential metabolites (DMs) were identified, of which, Equol was down-regulated in GTN patients, whose VIP score is the 3rd highest among the 24 DMs. As an intestinal metabolite of daidzein, the anticancer potential of Equol has been demonstrated in multiple cancers, but not choriocarcinoma. Hence, human choriocarcinoma cell lines JEG-3 and Bewo were used and JEG-3-derived subcutaneous xenograft models were developed to assess the effect of Equol on choriocarcinoma. The results suggested that Equol treatment effectively suppressed choriocarcinoma cell proliferation, induced cell apoptosis, and reduced tumorigenesis. Label-free quantitative proteomics showed that 136 proteins were significantly affected by Equol and 20 proteins were enriched in Gene Ontology terms linked to protein degradation. Tripartite motif containing 21 (TRIM21), a E3 ubiquitin ligase, was up-regulated by Equol. Equol-induced effects on choriocarcinoma cells could be reversed by TRIM21 inhibition. Annexin A2 (ANXA2) interacted with TRIM21 and its ubiquitination was modulated by TRIM21. We found that TRIM21 was responsible for proteasome-mediated degradation of ANXA2 induced by Equol, and the inhibitory effects of Equol on the malignant behaviors of choriocarcinoma cells were realized by TRIM21-mediated down-regulation of ANXA2. Moreover, ß-catenin activation was inhibited by Equol, which also depended on TRIM21-mediated down-regulation of ANXA2. Taken together, Equol may be a novel candidate for the treatment for choriocarcinoma.

Serum taurine affects lung cancer progression by regulating tumor immune escape mediated by the immune microenvironment.

INTRODUCTION: Taurine is a naturally occurring sulfonic acid involved in various physiological and pathological processes, such as the regulation of calcium signaling, immune function, inflammatory response, and cellular aging. It has the potential to predict tumor malignant transformation and formation. Our previous work discovered the elevated taurine in lung cancer patients. However, the precise impact and mechanism of elevated serum taurine levels on lung cancer progression and the suitability of taurine or taurine-containing drinks for lung cancer patients remain unclear. OBJECTIVES: Our study aimed to systematically investigate the role of taurine in lung cancer, with the ultimate goal of contributing novel strategies for lung cancer treatment. METHODS: Lung cancer C57 and nude mice models, RNA sequencing, and stable transfection were applied to explored the effects and mechanisms of taurine on lung cancer. Tissues of 129 non-small cell lung cancer (NSCLC) patients derived from 2014 to 2017 for immunohistochemistry were collected in Taihe Hospital. RESULTS: Low doses of taurine, as well as taurine-infused beverages at equivalent doses, significantly enhanced lung tumor growth. Equally intriguing is that the promoting effect of taurine on lung cancer progression wanes as the dosage increases. The Nuclear factor erythroid 2-like 1 (Nfe2l1 or Nrf1)-reactive oxygen species (ROS)-PD-1 axis may be a potential mechanism for dual role of taurine in lung cancer progression. However, taurine's impacts on lung cancer progression and the anti-tumor function of Nfe2l1 were mainly determined by the immune competence. Taurine inhitited lung tumor growth probably by inhibiting NF-κB-mediated inflammatory responses in nude mice rather than by affecting Nfe2l1 function. As patients age increased, Nfe2l1 gene and protein gradually returned to the levels observed in healthy individuals, but lost its anti-lung cancer effects. CONCLUSIONS: Taurine emerges as a potential biomarker for lung cancer progression, predicting poor prognosis and unsuitability for specific patients. Lung cancer patients, especially young patients, should be conscious of potential effects of taurine-containing drinks. Conversely, taurine or its drinks may be more suitable for older or immune-deficient patients.

Chiral inorganic nanomaterials in the tumor microenvironment: A new chapter in cancer therapy.

Chirality plays a crucial function in the regulation of normal physiological processes and is widespread in organisms. Chirality can be imparted to nanomaterials, whether they are natural or manmade, through the process of asymmetric assembly and/or grafting of molecular chiral groups or linkers. Chiral inorganic nanomaterials possess unique physical and chemical features that set them apart from regular nanomaterials. They also have the ability to interact with cells and tissues in a specific manner, making them useful in various biomedical applications, particularly in the treatment of tumors. Despite the growing amount of research on chiral inorganic nanomaterials in the tumor microenvironment (TME) and their promising potential applications, there is a lack of literature that comprehensively summarizes the intricate interactions between chiral inorganic nanomaterials and TME. In this review, we introduce the fundamental concept, classification, synthesis methods, and physicochemical features of chiral inorganic nanomaterials. Next, we briefly outline the components of TME, such as T cells, macrophages, dendritic cells, and weak acids, and then discuss the anti-tumor effects of several chiral inorganic nanoparticles targeting these components and their potential for possible application during cancer therapy. Finally, the present challenges faced by chiral inorganic nanomaterials in cancer treatment and their future areas of investigation are disclosed.

Verapamil enhances the activity of Caspofungin against Cryptococcus neoformans， coinciding with inhibited Ca2+/CN pathway and damage to cell wall integrity.

OBJECTIVES: Given the challenges posed by toxicity and drug resistance in the treatment of cryptococcal infections, we sought to explore the antifungal potential of verapamil (VER), a calcium channel blocker, against Cryptococcus neoformans (C. neoformans), and its potential synergy with antifungals, specifically caspofungin (CAS). MATERIALS AND METHODS: In vitro and in vivo (Galleria mellonella) models were employed to assess VER's antifungal activity and its interaction with CAS. Mechanisms underlying the synergism were explored through analysis of cell wall integrity, membrane permeability, and gene expression related to the calcineurin pathway. Additionally, the influence of Ca2+ on chitin deacetylase activity was investigated. RESULTS: VER exhibited a pronounced antifungal effect on C. neoformans and synergized with CAS, enhancing antifungal efficacy in Galleria mellonella. VER reduced chitosan content and disrupted cell wall integrity, evidenced by melanin leakage and fluorescence staining. VER+CAS modified membrane permeability, triggering intracellular ROS accumulation and mitochondrial membrane potential alterations. VER mitigated CAS-induced calcium fluctuations and downregulated calcineurin pathway genes. Furthermore, it was found that the enzyme activity of chitin deacetylase of C. neoformans is significantly influenced by the presence of Ca2+, suggesting that the use of VER may affect this activity. CONCLUSIONS: The synergistic antifungal effect of VER and CAS represents a promising therapeutic strategy for cryptococcal infections. The multifaceted mechanisms, including disruption of cell wall integrity and modulation of membrane permeability, and regulation of intracellular calcium signaling pathways, offer new insights into antifungal drug development.

Chirality-dependent topological edge states in photonic metacrystal.

Topological edge state, a unique mode for manipulating electromagnetic waves (EMs), has been extensively studied in both fundamental and applied physics. Up to now, the work on topological edge states has focused on manipulating linearly polarized waves. Here, we realize chirality-dependent topological edge states in one-dimensional photonic crystals (1DPCs) to manipulate circularly polarized waves. By introducing the magneto-electric coupling term (chirality), the degeneracy Dirac point (DP) is opened in PCs with symmetric unit cells. The topological properties of the upper and lower bands are different in the cases of left circularly polarized (LCP) and right circularly polarized (RCP) waves by calculating the Zak phase. Moreover, mapping explicitly 1D Maxwell's equations to the Dirac equation, we demonstrate that the introduction of chirality can lead to different topological properties of bandgaps for RCP and LCP waves. Based on this chirality-dependent topology, we can further realize chirality-dependent topological edge states in photonic heterostructures composed of two kinds of PCs. Finally, we propose a realistic structure for the chirality-dependent topological edge states by placing metallic helixes in host media. Our work provides a method for manipulating topological edge states for circularly polarized waves, which has a broad range of potential applications in designing optical devices including polarizers, filters, and sensors with robustness against disorder.

Spinal Infections? mNGS Combined with Microculture and Pathology for Answers.

Introduction: This study evaluates the efficacy of metagenomic next-generation sequencing (mNGS) in diagnosing spinal infections and developing therapeutic regimens that combine mNGS, microbiological cultures, and pathological investigations. Methods: Data were collected from 108 patients with suspected spinal infections between January 2022 and December 2023. Lesion tissues were obtained via C-arm assisted puncture or open surgery for mNGS, conventional microbiological culture, and pathological analysis. Personalized antimicrobial therapies were tailored based on these findings, with follow-up evaluations 7 days postoperatively. The sensitivity and specificity of mNGS were assessed, along with its impact on treatment and prognosis. Results: mNGS showed a significantly higher positive detection rate (61.20%) compared to conventional microbiological culture (30.80%) and PCT (28%). mNGS demonstrated greater sensitivity (79.41%) and negative predictive value (63.16%) than cultures (25% and 22.58%, respectively), with no significant difference in specificity and positive predictive value. Seven days post-surgery, a significant reduction in neutrophil percentage (NEUT%) was observed, though decreases in white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were not statistically significant. At the last follow-up, significant improved in Visual Analogue Scale (VAS) scores, Oswestry Disability Index (ODI), and Japanese Orthopaedic Association (JOA) scores were noted. Conclusion: mNGS outperforms traditional microbiological culture in pathogen detection, especially for rare and critical pathogens. Treatment protocols combining mNGS, microbiological cultures, and pathological examinations are effective and provide valuable clinical insights for treating spinal infections.

PARP4 interacts with hnRNPM to regulate splicing during lung cancer progression.

BACKGROUND: The identification of cancer driver genes from sequencing data has been crucial in deepening our understanding of tumor biology and expanding targeted therapy options. However, apart from the most commonly altered genes, the mechanisms underlying the contribution of other mutations to cancer acquisition remain understudied. Leveraging on our whole-exome sequencing of the largest Asian lung adenocarcinoma (LUAD) cohort (n = 302), we now functionally assess the mechanistic role of a novel driver, PARP4. METHODS: In vitro and in vivo tumorigenicity assays were used to study the functional effects of PARP4 loss and mutation in multiple lung cancer cell lines. Interactomics analysis by quantitative mass spectrometry was conducted to identify PARP4's interaction partners. Transcriptomic data from cell lines and patient tumors were used to investigate splicing alterations. RESULTS: PARP4 depletion or mutation (I1039T) promotes the tumorigenicity of KRAS- or EGFR-driven lung cancer cells. Disruption of the vault complex, with which PARP4 is commonly associated, did not alter tumorigenicity, indicating that PARP4's tumor suppressive activity is mediated independently. The splicing regulator hnRNPM is a potentially novel PARP4 interaction partner, the loss of which likewise promotes tumor formation. hnRNPM loss results in splicing perturbations, with a propensity for dysregulated intronic splicing that was similarly observed in PARP4 knockdown cells and in LUAD cohort patients with PARP4 copy number loss. CONCLUSIONS: PARP4 is a novel modulator of lung adenocarcinoma, where its tumor suppressive activity is mediated not through the vault complex-unlike conventionally thought, but in association with its novel interaction partner hnRNPM, thus suggesting a role for splicing dysregulation in LUAD tumorigenesis.

Microglial AKAP8L: a key mediator in diabetes-associated cognitive impairment via autophagy inhibition and neuroinflammation triggering.

BACKGROUND: Diabetes-associated cognitive impairment (DACI) poses a significant challenge to the self-management of diabetes, markedly elevating the risk of adverse complications. A burgeoning body of evidence implicates microglia as a central player in the pathogenesis of DACI. METHODS: We utilized proteomics to identify potential biomarkers in high glucose (HG)-treated microglia, followed by gene knockdown techniques for mechanistic validation in vitro and in vivo. RESULTS: Our proteomic analysis identified a significant upregulation of AKAP8L in HG-treated microglia, with concurrent dysregulation of autophagy and inflammation markers, making AKAP8L a novel biomarker of interest. Notably, the accumulation of AKAP8L was specific to HG-treated microglia, with no observed changes in co-cultured astrocytes or neurons, a pattern that was mirrored in streptozotocin (STZ)-induced diabetic mice. Further studies through co-immunoprecipitation and proximity ligation assay indicated that the elevated AKAP8L in HG-treated microglial cells interacts with the mTORC1. In the STZ mouse model, we demonstrated that both AKAP8L knockdown and rapamycin treatment significantly enhanced cognitive function, as evidenced by improved performance in the Morris water maze, and reduced microglial activation. Moreover, these interventions effectively suppressed mTORC1 signaling, normalized autophagic flux, mitigated neuroinflammation, and decreased pyroptosis. CONCLUSIONS: Our findings highlight the critical role of AKAP8L in the development of DACI. By interacting with mTORC1, AKAP8L appears to obstruct autophagic processes and initiate a cascade of neuroinflammatory responses. The identification of AKAP8L as a key mediator in DACI opens up new avenues for potential therapeutic interventions.

Longitudinal association between maternal cardiovascular health in pregnancy and child birth outcomes.

The American Heart Association has updated its definition of cardiovascular health (CVH) with a new framework known as Life's Essential 8 (LE8). Although gestational CVH assessment has been recommended, its significance based on LE8 for birth outcomes is unknown. We thus evaluated the status of gestational CVH based on LE8 in 3036 pregnant women of the Shanghai Maternal-Child Pairs Cohort and the population of China Maternal Nutrition and Health Sciences Survey, and also examined the association between gestational CVH and child birth outcomes. We found that only a small proportion (12.84%) had high CVH, while 1.98% had low CVH in this cohort study. In adjusted models, a 10-point increase in the gestational CVH score, indicating a more favorable score, was associated with lower neonatal size such as birth weight (ß: - 37.05 [95% confidence interval: - 52.93, - 21.16]), birth length (- 0.12[- 0.22, - 0.01]), weight-for-height z-score (- 0.07[- 0.12, - 0.03]), body mass index z-score (- 0.09 [- 0.13, - 0.04]), length-for-age Z-score (- 0.03 [- 0.06, - 0.01]), and weight-for-age z-score (- 0.08 [- 0.12, - 0.05]). Also, a 10-point increase in the gestational CVH score was associated with the lower risk of large for gestational age (LGA) (0.82 [0.73, 0.92]) and macrosomia infant (0.75 [0.64, 0.88]). CVH categories showed similar results. That is, better maternal CVH status in pregnancy was associated with lower neonatal size and lower risks for LGA and macrosomia in newborns.

Development and validation of a prediction model for hypoproteinemia after traumatic spinal cord injury: A multicenter retrospective clinical study.

A multicenter retrospective analysis of conventionally collected data. To identify the potential causes of hypoproteinemia after traumatic spinal cord injury (TSCI) and provide a diagnostic model for predicting an individual likelihood of developing hypoproteinemia. Hypoproteinemia is a complication of spinal cord injury (SCI), an independent risk factor for respiratory failure in elderly patients with SCI, and a predictor of outcomes in patients with cervical SCI. Few nomogram-based studies have used clinical indicators to predict the likelihood of hypoproteinemia following TSCI. This multicenter retrospective clinical analysis included patients with TSCI admitted to the First Affiliated Hospital of Guangxi Medical University, Wuzhou GongRen Hospital, and Dahua Yao Autonomous County People Hospital between 2016 and 2020. The data of patients from the First Affiliated Hospital of Guangxi Medical University were used as the training set, and those from the other 2 hospitals were used as the validation set. All patient histories, diagnostic procedures, and imaging findings were recorded. To predict whether patients with TSCI may develop hypoproteinemia, a least absolute shrinkage and selection operator regression analysis was conducted to create a nomogram. The model was validated by analyzing the consequences using decision curve analysis, calibration curves, the C-index, and receiver operating characteristic curves. After excluding patients with missing data, 534 patients were included in this study. Male/female sex, age ≥ 60 years, cervical SCI, pneumonia, pleural effusion, urinary tract infection (UTI), hyponatremia, fever, hypotension, and tracheostomy were identified as independent risk factors of hypoalbuminemia. A simple and easy-to-replicate clinical prediction nomogram was constructed using these factors. The area under the curve was 0.728 in the training set and 0.881 in the validation set. The predictive power of the nomogram was satisfactory. Hypoalbuminemia after TSCI may be predicted using the risk factors of male/female sex, age ≥ 60 years, cervical SCI, pneumonia, pleural effusion, UTI, hyponatremia, fever, hypotension, and tracheostomy.

Nationwide law enforcement impact on the pet bird trade in China.

Conservation enforcement is a direct strategy to combat illegal wildlife trade in open markets. Yet, its large-scale effectiveness has not been widely assessed due to the lack of extensive market data. Between August 2016 and June 2017, a national coordinated enforcement campaign led by the leading Chinese authority to combat illegal migratory bird trade coincided with the largest-ever pet bird market survey across China by voluntary birdwatchers before and after the enforcement, which served as a unique natural experiment. Across 73 markets from 22 Chinese provinces, the dataset contains 140,723 birds of 346 species from 48 families and recorded a drastic decline in bird abundance traded after enforcement. Notably, species protected under China's Wildlife Protection Law declined significantly, while commercially bred species increased, although responses to enforcement were spatially heterogeneous. Our model showed that the national protection level was the best predictor for the trend of traded species, even after accounting for confounding factors such as regional baseline enforcement pressure and wild native bird populations. However, the widely traded native songbirds were not offered adequate national protection. Future policies should consider the pet bird trade patterns, target key areas of trade, and develop a more systematic market survey design to monitor trade.

Genomic profiling informs therapies and prognosis for patients with hepatocellular carcinoma in clinical practice.

Hepatocellular carcinoma (HCC) genomic research has discovered actionable genetic changes that might guide treatment decisions and clinical trials. Nonetheless, due to a lack of large-scale multicenter clinical validation, these putative targets have not been converted into patient survival advantages. So, it's crucial to ascertain whether genetic analysis is clinically feasible, useful, and whether it can be advantageous for patients. We sequenced tumour tissue and blood samples (as normal controls) from 111 Chinese HCC patients at Qingdao University Hospital using the 508-gene panel and the 688-gene panel, respectively. Approximately 95% of patients had gene variations related to targeted treatment, with 50% having clinically actionable mutations that offered significant information for targeted therapy. Immune cell infiltration was enhanced in individuals with TP53 mutations but decreased in patients with CTNNB1 and KMT2D mutations. More notably, we discovered that SPEN, EPPK1, and BRCA2 mutations were related to decreased median overall survival, although MUC16 mutations were not. Furthermore, we found mutant MUC16 as an independent protective factor for the prognosis of HCC patients after curative hepatectomy. In conclusion, this study connects genetic abnormalities to clinical practice and potentially identifies individuals with poor prognoses who may benefit from targeted treatment or immunotherapy.

Identification of Drought-Resistant Response in Proso Millet (Panicum miliaceum L.) Root through Physiological and Transcriptomic Analysis.

Proso millet (Panicum miliaceum L.) is resilient to abiotic stress, especially to drought. However, the mechanisms by which its roots adapt and tolerate salt stress are obscure. In this study, to clarify the molecular mechanism of proso millet in response to drought stress, the physiological indexes and transcriptome in the root of seedlings of the proso millet cultivar 'Yumi 2' were analyzed at 0, 0.5, 1.0, 1.5, and 3.0 h of stimulated drought stress by using 20% PEG-6000 and after 24 h of rehydration. The results showed that the SOD activity, POD activity, soluble protein content, MDA, and O2-· content of 'Yumi 2' increased with the time of drought stress, but rapidly decreased after rehydration. Here, 130.46 Gb of clean data from 18 samples were obtained, and the Q30 value of each sample exceeded 92%. Compared with 0 h, the number of differentially expressed genes (DEGs) reached the maximum of 16,105 after 3 h of drought, including 9153 upregulated DEGs and 6952 downregulated DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that upregulated DEGs were mainly involved in ATP binding, nucleus, protein serine/threonine phosphatase activity, MAPK signaling pathway-plant, plant-pathogen interactions, and plant hormone signal transduction under drought stress, while downregulated DEGs were mainly involved in metal ion binding, transmembrane transporter activity, and phenylpropanoid biosynthesis. Additionally, 1441 TFs screened from DEGs were clustered into 64 TF families, such as AP2/ERF-ERF, bHLH, WRKY, NAC, MYB, and bZIP TF families. Genes related to physiological traits were closely related to starch and sucrose metabolism, phenylpropanoid biosynthesis, glutathione metabolism, and plant hormone signal transduction. In conclusion, the active oxygen metabolism system and the soluble protein of proso millet root could be regulated by the activity of protein serine/threonine phosphatase. AP2/ERF-ERF, bHLH, WRKY, NAC, MYB, and bZIP TF families were found to be closely associated with drought tolerance in proso millet root. This study will provide data to support a subsequent study on the function of the drought tolerance gene in proso millet.

Prospective associations of maternal cardiometabolic health with children cardiometabolic health at ages 3 to 6 years.

OBJECTIVE: Maternal cardiometabolic health (MCMH) may have critical effects on offspring lifetime CMH, whereas evidence on the relationship between MCMH during pregnancy and children CMH (CCMH) at ages 3∼6 years remains unknown. METHOD: The study included 1478 mother-child dyads from the Shanghai Maternal-Child Pairs Cohort study. MCMH was examined at a mean of 27.8 (24-36) weeks' gestation based on 8 metrics of 'Life Essential 8' framework involving pre-pregnancy body mass index, total cholesterol, glucose level, blood pressure, physical activity, sleep, diet quality, and nicotine exposure. CCMH was examined at the age of 3 to 6 based on 5 metrics including body mass index, physical activity, sleep health, diet quality, and nicotine exposure. To validate the robustness of main analysis, 499 children were selected to reevaluate CCMH by six metrics (adding blood pressure) for sensitivity analysis. RESULTS: Among 1478 mother-child dyads, the mean (SD) MCMH during pregnancy and CCMH scores were 67.07 (SD 8.82) and 73.80 (SD 10.75), respectively. After adjusting important confounders, each 10 points increase in (more favorable) MCMH score was significantly associated with a higher CCMH score (ß: 0.85, [95% confidence interval (CI): 0.22, 1.47]). Subgroup analysis showed similar results in girls but not in boys. For cardiometabolic risks factors in children, the risk of overweight/obesity and hypertension in children decreased with increased MCMH score (overweight/obesity, Relative Risks [RRs]: 0.98, 95%CI: [0.96, 0.99]); hypertension, RRs: 0.66, 95%CI: [0.47, 0.92]). Sensitivity analysis showed similar result. CONCLUSIONS: Better MCMH in pregnancy was associated with better CCMH at ages 3∼6 years.

[Altitude Distribution Characteristics of Farmland Soil Bacteria in Loess Hilly Region of Ningxia].

It is of great significance for the conservation of biodiversity in farmland ecosystems to study the diversity, structure, functions, and biogeographical distribution of soil microbes in farmland and their influencing factors. High-throughput sequencing technology was used to analyze the distribution characteristics of soil bacterial diversity, community structure, and metabolic function along elevation and their responses to soil physicochemical properties in farmland in the loess hilly areas of Ningxia. The results showed that:① The Alpha diversity index of soil bacterial was significantly negatively correlated with elevation (P < 0.05) and showed a trend of decreasing and then slightly increasing along the elevation. ② Seven phyla, including Proteobacteria, Actinobacteria, and Acidobacteria, were the dominant groups, and five of them showed highly significant differences between altitudes (P < 0.01). ③ At the secondary classification level, there were 36 metabolic functions of bacteria, including membrane transport, carbohydrate metabolism, and amino acid metabolism, of which 22 showed significant differences, and 12 showed extremely significant differences among different altitudes. ④ Pearson correlation analysis showed that soil water content, bulk density, pH, and carbon-nitrogen ratio had the most significant effects on bacterial Alpha diversity, whereas soil nutrients such as total organic carbon, total nitrogen, and total phosphorus had significant effects on bacterial Beta diversity. ⑤ Mantel test analysis showed that the soil water content, total organic carbon, and carbon-nitrogen ratio affected bacterial community structure at the phylum level, and soil pH, total organic carbon, total nitrogen, total phosphorus, and carbon-nitrogen ratio were significantly correlated with bacterial metabolic function. Variance partitioning analysis showed that soil water content had the highest explanation for the community structure of soil bacteria, whereas soil pH had the highest explanation for metabolic function. In conclusion, soil water content and pH were the main factors affecting the diversity, community composition, and metabolic function of soil bacteria in farmland in the loess hilly region of Ningxia.

circCDK13-loaded small extracellular vesicles accelerate healing in preclinical diabetic wound models.

Chronic wounds are a major complication in patients with diabetes. Here, we identify a therapeutic circRNA and load it into small extracellular vesicles (sEVs) to treat diabetic wounds in preclinical models. We show that circCDK13 can stimulate the proliferation and migration of human dermal fibroblasts and human epidermal keratinocytes by interacting with insulin-like growth factor 2 mRNA binding protein 3 in an N6-Methyladenosine-dependent manner to enhance CD44 and c-MYC expression. We engineered sEVs that overexpress circCDK13 and show that local subcutaneous injection into male db/db diabetic mouse wounds and wounds of streptozotocin-induced type I male diabetic rats could accelerate wound healing and skin appendage regeneration. Our study demonstrates that the delivery of circCDK13 in sEVs may present an option for diabetic wound treatment.