Müller cells are activated in response to retinal outer nuclear layer degeneration in rats subjected to simulated weightlessness conditions.

JOURNAL/nrgr/04.03/01300535-202507000-00032/figure1/v/2024-09-09T124005Z/r/image-tiff A microgravity environment has been shown to cause ocular damage and affect visual acuity, but the underlying mechanisms remain unclear. Therefore, we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under microgravity. After 4 weeks of tail suspension, there were no notable alterations in retinal function and morphology, while after 8 weeks of tail suspension, significant reductions in retinal function were observed, and the outer nuclear layer was thinner, with abundant apoptotic cells. To investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina, proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail suspension. The results showed that the expression levels of fibroblast growth factor 2 (also known as basic fibroblast growth factor) and glial fibrillary acidic protein, which are closely related to Müller cell activation, were significantly upregulated. In addition, Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks, respectively, of simulated weightlessness. These findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.

Engineering Two-dimensional tungsten-doped molybdenum selenide transformed conformational nanoarchitectonics: Trimodal therapeutic nanoagents for enhanced synergistic Photothermal/Chemodynamic/Chemotherapy of breast carcinoma.

Two-dimensional transition metal dichalcogenides (TMDCs) exhibit promising photothermal therapy (PTT) and chemodynamic therapy (CDT) for anti-tumour treatment. Herein, we proposed an engineering strategy to regulate the lattice structure of tungsten-doped molybdenum selenide (MoxW1-xSe2) transformed conformational nanoarchitectonics using a microwave-assisted solvothermal method for enhancing peroxidase (POD)-like catalytic performance by adjusting the ratio of molybdenum (Mo) and tungsten (W). Furthermore, the optimised Mo0.8W0.2Se2 nanoflakes surface was modified with chitosan (CHI) for improved biocompatibility and nanocatalytic efficacy, then the obtained CHI-Mo0.8W0.2Se2 subsequently loaded the chemotherapeutic drug mitoxantrone (MTO) for enhanced 4 T1 cells killing ability, shortly denoted as CHI-Mo0.8W0.2Se2-MTO for PTT-augmented CDT and chemotherapy (CT). A series of performance validations successfully showed that electrons tend to transfer from W to Mo in CHI-Mo0.8W0.2Se2, which resulted in superior POD-like activity (Km = 0.038 mM) of CHI-Mo0.8W0.2Se2 compared with that of horseradish peroxidase. Furthermore, CHI-Mo0.8W0.2Se2-MTO with excellent photothermal conversion efficiency (PCE=63.2 %) in the near-infrared (NIR) region could further promote endogenous •OH generation and MTO controlled release within solid tumours. In vivo studies confirmed the successful achievement of synergistic therapeutic effects (tumour inhibition rate of over 90 %) with minimised side effects. Versatile therapeutic nanoagents hold great potential for personalised therapy of breast cancer and will find their way to the pharmaceutical field.

Polar Thiazole Derivative-Induced Second Harmonic Response in Hybrid Bismuth Chlorate with Reversible Photochromism.

Inorganic-organic hybrid bismuth halides demonstrate great prospect in the field of second-order nonlinear optical (NLO) crystals because the ns2 electron on Bi(III) could lead to large molecular polarization and high second harmonic generation (SHG) coefficient on a noncentrosymmetric structure. However, researchers cannot yet control the effective arrangements of the bismuth halide functional motif, which results in SHG-active hybrid bismuth halides being rare. Herein, thiazole derivatives with a polar donor-π-acceptor system are designed to explore hybrid bismuth halide NLO crystals. The protonated 2-(4-hydroxyphenyl) thiazole (denoted as hpt) interacts with the (BiCl6) motif via H···Cl hydrogen bonds to prevent antiparallel arrangements, which therefore enhance the NLO property. (Hhpt)3[BiCl6] crystallizes in the monoclinic polar P21 space group, which exhibits a strong SHG response and reversible photochromic behavior. Structural analysis and theory calculations reveal that the synergistic effect between the polar thiazole derivative and the distorted inorganic [BiCl6]3- motif is responsible for the SHG response. This is the first report of polar thiazole derivative-induced SHG-active hybrid bismuth halide coupled with reversible photochromism.

A new strategy for the treatment of intracerebral hemorrhage: Ferroptosis.

Intracerebral hemorrhage, is a cerebrovascular disease with high morbidity, mortality, and disability. Due to the lack of effective clinical treatments, the development of new drugs to treat intracerebral hemorrhage is necessary. In recent years, ferroptosis has been found to play an important role in the pathophysiological process of intracerebral hemorrhage, which can be treated by inhibiting ferroptosis and thus intracerebral hemorrhage. This article aims to explain the mechanism of ferroptosis and its relationship to intracerebral hemorrhage. In the meantime, it briefly discusses the molecules identified to alleviate intracerebral hemorrhage by inhibiting ferroptosis, along with other clinical agents that are expected to treat intracerebral hemorrhage through this mechanism. In addition, a brief overview of the morphological alterations of different forms of cell death and their role in ICH is provided. Finally, the challenges that may arise in translating ferroptosis inhibitors from basic research to clinical use are presented. This article serves as a reference and provides insights to aid in the treatment of intracerebral hemorrhage in the clinic.

Disulfidptosis and ferroptosis related genes define the immune microenvironment and NUBPL serves as a potential biomarker for predicting prognosis and immunotherapy response in bladder cancer.

Background: Ferroptosis and disulfidptosis are regulatory forms of cell death that play an important role in tumorigenesis and progression. However, few biomarkers about disulfidptosis and ferroptosis related genes (DFRGs) have been developed to predict the prognosis of bladder cancer (BC). Methods: We conducted a bioinformatics analysis using public BC datasets to examine the prognostic significance of differentially expressed DFRGs. A Lasso regression was employed to create a prognostic prediction model from these DFRGs. Hub DFRGs that play a role in immunotherapy response and immunoregulation were pinpointed. Immunohistochemistry (IHC) experiment was performed to assess NUBPL and c-MYC expression in BC patients who underwent surgery or received immune checkpoint inhibitor (ICI) immunotherapy at Peking University Cancer Hospital. Results: We constructed a valid model to predict the prognosis of BC based on DFRGs and performed relevant validation, the results demonstrated that the model was an independent prognostic factor for BC. Further analysis indicated that the model score, combined with the expression of various immune factors and tumor mutation burden (TMB), could predict the prognosis for BC. In addition, we also found that NUBPL was strongly associated with prognosis and response to ICI treatment, and NUBPL may influence BC malignant progression through the c-MYC pathway. Conclusions: Our research findings highlight the satisfactory predictive value of DFRGs in the immune microenvironment and suggest that NUBPL may be a highly promising biomarker for predicting the prognosis and efficacy of ICI treatment in BC patients.

Ursodeoxycholic Acid Platinum(IV) Conjugates as Antiproliferative and Antimetastatic Agents: Remodel the Tumor Microenvironment through Suppressing JAK2/STAT3 Signaling.

Tumor microenvironment (TME) is a pivotal factor driving the tumor metastasis and leading to the failure of tumor therapy. Here, a series of ursodeoxycholic acid platinum(IV) conjugates with potency in remodeling the TME through suppressing JAK2/STAT3 signaling was developed. A candidate was screened out, which displayed potent antiproliferative and antimetastatic performance both in vitro and in vivo. It displayed superior pharmacokinetic properties compared to cisplatin. Serious DNA injury was induced, and then mitochondria-mediated apoptosis was initiated through the Bcl-2/Bax/Caspase3 pathway. The JAK2/STAT3 and TGF-ß1 signaling pathways were remarkably inhibited, and pro-death autophagy was subsequently promoted. The inflammatory and hypoxic TME was suppressed by downregulating COX-2, MMP9, and HIF-1α, which resulted in inhibited angiogenesis in tumors by inhibiting the HIF-1α/VEGFA axis. Additionally, the immunosuppressive TME was reversed by blocking the immune checkpoint PD-L1, further improving the density of CD3+ and CD8+ tumor-infiltrating lymphocytes, and promoting macrophage polarization from M2- to M1-type.

An Improved YOLOv8 OBB Model for Ship Detection through Stable Diffusion Data Augmentation.

Unmanned aerial vehicles (UAVs) with cameras offer extensive monitoring capabilities and exceptional maneuverability, making them ideal for real-time ship detection and effective ship management. However, ship detection by camera-equipped UAVs faces challenges when it comes to multi-viewpoints, multi-scales, environmental variability, and dataset scarcity. To overcome these challenges, we proposed a data augmentation method based on stable diffusion to generate new images for expanding the dataset. Additionally, we improve the YOLOv8n OBB model by incorporating the BiFPN structure and EMA module, enhancing its ability to detect multi-viewpoint and multi-scale ship instances. Through multiple comparative experiments, we evaluated the effectiveness of our proposed data augmentation method and the improved model. The results indicated that our proposed data augmentation method is effective for low-volume datasets with complex object features. The YOLOv8n-BiFPN-EMA OBB model we proposed performed well in detecting multi-viewpoint and multi-scale ship instances, achieving the mAP (@0.5) of 92.3%, the mAP (@0.5:0.95) of 77.5%, a reduction of 0.8 million in model parameters, and a detection speed that satisfies real-time ship detection requirements.

Positional information modulates transient regeneration-activated cell states during vertebrate appendage regeneration.

Injury is common in the life of organisms. Because the extent of damage cannot be predicted, injured organisms must determine how much tissue needs to be restored. Although it is known that amputation position affects the regeneration speed of appendages, mechanisms conveying positional information remain unclear. We investigated tissue dynamics in regenerating caudal fins of the African killifish (Nothobranchius furzeri) and found position-specific, differential spatial distribution modulation, persistence, and magnitude of proliferation. Single-cell RNA sequencing revealed a transient regeneration-activated cell state (TRACS) in the basal epidermis that is amplified to match a given amputation position and expresses components and modifiers of the extracellular matrix (ECM). Notably, CRISPR-Cas9-mediated deletion of the ECM modifier sequestosome 1 (sqstm1) increased the regenerative capacity of distal injuries, suggesting that regeneration growth rate can be uncoupled from amputation position. We propose that basal epidermis TRACS transduce positional information to the regenerating blastema by remodeling the ECM.

Atlas of mildly and highly insoluble matrisome driving liver fibrosis.

The excessive deposition and cross-linking of core matrisome components typically result in abnormal remodeling of the extracellular matrix (ECM), leading to increased liver stiffness and worsening liver fibrosis. Exploring the biochemical properties of the ECM scaffold can deepen our understanding of the pathological mechanisms driving liver fibrosis and potentially facilitate the identification of therapeutic targets. While traditional sodium dodecyl sulfate (SDS)-based liver decellularization followed by proteomics can uncover the matrisome components within the ECM scaffold, it lacks the ability to reveal physicochemical characteristics like solubility. In our present study, using adult mouse liver as an example, we introduced a novel two-step workflow that combines our previously enhanced SDS (ESDS) decellularization with the conventional SDS method, enabling the identification of matrisome members with mild and/or high solubilities. Through this approach, we visualized the atlas of the mildly and highly insoluble matrisome contents in the adult mouse liver, as well as the regulatory network of highly insoluble matrisome that largely governs liver stiffness. Given the strong correlation between increased matrisome insolubility and heightened ECM stiffness, we believe that this methodology holds promise for future research focused on liver stiffness.

Proteomic Analysis Reveals Differential Protein Expression in Placental Tissues of Early-Onset Preeclampsia Patients.

Preeclampsia, a significant cause of maternal and perinatal morbidity and mortality, remains poorly understood, in terms of its pathogenesis. This study aims to uncover novel and effective biomarkers for preeclampsia by conducting a comparative analysis of differential proteins in placentas from early onset preeclampsia (EOPE) and normal pregnancies. Utilizing tandem mass tag (TMT)-based quantitative proteomics, we identified differentially expressed proteins in placental tissues from 15 EOPE patients and 15 normal pregnant women. These proteins were subsequently validated by using parallel reaction monitoring (PRM). Our analysis revealed a total of 59 differentially expressed proteins, with 25 up-regulated and 34 down-regulated proteins in EOPE placental tissues compared to those from normal pregnancies. Validation through PRM confirmed the differential expression of 6 proteins. Our findings suggest these 6 proteins could play crucial roles in the pathogenesis of EOPE, highlighting the potential involvement of the estrogen signaling pathway and dilated cardiomyopathy (DCM) pathway in the development of preeclampsia. The data were deposited with the ProteomeXchange Consortium via the iProX partner repository with the identifier PXD055025.

Dysregulated Mitochondrial Calcium Causes Spiral Artery Remodeling Failure in Preeclampsia.

BACKGROUND: Calcium deficiency in women is strongly linked to an increased risk of developing preeclampsia. Mitochondrial calcium ([Ca2+]m) homeostasis is essential to regulate vascular smooth muscle cell (VSMC) function. However, the role of [Ca2+]m in preeclampsia development remains largely unknown. METHODS: To investigate this, human spiral arteries obtained from normotensive and preeclamptic women were collected for vascular function, RNA sequencing, and VSMC studies. N(ω)-nitro-L-arginine methyl ester-induced preeclampsia animal experiments were established to investigate the effects of intervening in [Ca2+]m to improve the outcome for preeclamptic mothers or their infants. RESULTS: Our initial findings revealed compromised vessel function in spiral arteries derived from patients with preeclampsia, as evidenced by diminished vasoconstriction and vasodilation responses to angiotensin II and sodium nitroprusside, respectively. Moreover, the spiral artery VSMCs from patients with preeclampsia exhibited phenotypic transformation and proliferation associated with the disrupted regulatory mechanisms of [Ca2+]m uptake. Subsequent in vitro experiments employing gain- and loss-of-function approaches demonstrated that the mitochondrial Na+/Ca2+ exchanger played a role in promoting phenotypic switching and impaired mitochondrial functions in VSMCs. Furthermore, mtNCLX (mitochondrial Na+/Ca2+ exchanger) inhibitor CGP37157 significantly improved VSMC phenotypic changes and restored mitochondrial function in both patients with preeclampsia-derived VSMCs and the preeclampsia rat model. CONCLUSIONS: This study provides comprehensive evidence supporting the disrupted regulatory mechanisms of [Ca2+]m uptake in VSMCs of spiral arteries of patients with preeclampsia and further elucidates its correlation with VSMC phenotypic switching and defective spiral artery remodeling. The findings suggest that targeting mtNCLX holds promise as a novel therapeutic approach for managing preeclampsia.

Climate change and tourism demand: Risks for extreme heat?

Extremely high temperatures have become a major hurdle to tourists' experiences in various destinations. In this study, we present the first nationwide estimation of the temperature-tourism response function using a fine-grained panel dataset constructed by matching tourism data and daily meteorological datasets for 280 cities from 2005 to 2019 in China. Results show a non-linear relationship between temperature and tourism employing the temperature bins method, which is not sensitive to response equations. In addition, we conduct a rich heterogeneity analysis in the article to further analyse the effects of other external conditions on the temperature-tourism relationship, including the destination's level of tourism economic development, population, infrastructure development, and tourism resource endowment. We also observed that increasing summer temperatures result in decreased tourism arrivals and revenue, while rising autumn temperatures lead to increased tourism arrivals and revenue. This research contributes to a deeper understanding of the complex relationship between temperature dynamics and tourism patterns, offering insights into destination management and adaptation strategies.

Predicting survival in sepsis: The prognostic value of NLR and BAR ratios.

BACKGROUND: Due to the high-risk nature of sepsis, emergency departments urgently need a simple evaluation method to assess the degree of inflammation and prognosis in sepsis patients, providing a reference for diagnosis and treatment. OBJECTIVE: To investigate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) combined with the blood urea nitrogen-to-serum albumin ratio (BAR) in sepsis. METHODS: A total of 377 sepsis patients admitted to Lishui People's Hospital from June 2022 to June 2023 were selected as the study subjects. Based on their prognosis, they were divided into a survival group (255 cases) and a death group (82 cases). The clinical data of the two groups were compared. Multivariate logistic analysis was used to identify factors influencing sepsis prognosis, and ROC curve analysis was used to assess the predictive efficacy of NLR, BAR, and their combination. RESULTS: Compared with survivors, non-survivors had higher NLR and BAR, with statistically significant differences (p< 0.05). After adjusting for confounding factors, NLR (OR = 1.052) and BAR (OR = 1.095) were found to be independent prognostic factors for sepsis patients (both p< 0.05). The AUC of NLR combined with BAR was 0.798 (95% CI 0.745-0.850, p< 0.05), higher than the AUC of NLR alone (0.776) and BAR alone (0.701). CONCLUSIONS: The combination of NLR and BAR has a high predictive value for the prognosis of sepsis patients. Its simple calculation makes it particularly suitable for use in emergency departments.

Association between compound extreme weather event types and the spectrum of emergency ambulance calls: A metropolitan study in Shenzhen.

BACKGROUND: Compound extreme weather events, a combination of weather and climate drivers that lead to potentially high-impact events, are becoming more frequent with climate change. The number of emergency ambulance calls (EACs) is expected to increase during compound extreme weather events. However, the extent of these increases and the trends over time have not been fully assessed. METHODS: We obtained 242,165 EAC records for Shenzhen from January 1, 2020, to June 30, 2023. A compound extreme weather event was defined as the occurrence of at least two extreme weather events on the same day. A distributed lag non-linear model was used to explore the exposure-response and lag-response relationships between various compound extreme weather events and all-cause and specific-cause EACs. FINDING: Compound Cold & Strong Monsoon events had more significant impacts on EACs for all causes and endocrine diseases, with the cumulative relative risk (CRR) of 1.401 (95% confidence interval (CI):1.290-1.522) and 1.641 (95% CI:1.279-2.105). Compound Heat Wave & Lightning events had more obvious impacts on digestive disease and endocrine disease EACs, with the CRRs of 1.185 (95% CI:1.041-1.348) and 1.278 (95% CI:0.954-1.711), respectively. Compound Rainstorm & Lightning & Heat Wave events also led to increased RRs of EACs for all causes (CRR: 1.168, 95% CI:1.012-1.348), cardiovascular diseases (CRR: 1.221, 95% CI:0.917-1.624), digestive diseases (CRR: 1.395, 95% CI:1.130-1.721), and endocrine diseases (CRR: 1.972, 95% CI:1.235-3.149). There was no increased RR in the compound Rainstorm & Lightning events for all types of EACs. INTERPRETATION: Our study explored the relationship between EACs and compound extreme weather events, suggesting that compound extreme weather events are associated with the acute onset of cardiovascular diseases, digestive diseases, and endocrine diseases, increasing the burden on emergency ambulance resources for both all causes and specific diseases mentioned above.

Cortical activation during the verbal fluency task for obstructive sleep apnea patients with depressive symptoms: A multi-channel fNIRS study.

STUDY OBJECTIVE: The aim of our study was to elucidate differences in brain activity patterns among obstructive sleep apnea (OSA) patients, OSA patients with depressive symptoms, and healthy controls (HCs). We also investigated the relationship between brain function and depression in OSA patients. METHODS: A total of 95 subjects were included in the study, including 34 OSA patients without depressive symptoms, 31 OSA patients with depressive symptoms, and 30 HCs. The 53-channel functional near-infrared spectroscopy (fNIRS) was used to monitor the concentration of oxy-hemoglobin (Oxy-Hb) in the brain, whereas the participants performed the verbal fluency task, and the degree of depression was scored using the 17-item Hamilton Rating Scale for Depression (HAMD-17). Hierarchical regression models were conducted to analyze the association of fNIRS features with depressive symptom. RESULTS: The Oxy-Hb changes of the three groups were significantly different in Channels 25 (H = 9.878, p = .007) and 43 (H = 6.957, p = .031). Inter-group comparisons showed that the Oxy-Hb change of Channel 25 (located in the dorsolateral prefrontal cortex [DLPFC]) in OSA group was less than that in HC group (p = .006), and the Oxy-Hb change of Channel 43 (located in the right frontal polar region) in OSA group with depression was less than that in OSA group (p = .025). Spearman's test showed that there was a significant negative correlation between HAMD-17 scores and mean Oxy-Hb changes in Channel 43 (r = -.319, p < .05) in the OSA patients. Using hierarchical regression, Oxy-Hb changes in Channel 43 accounted for a significant proportion of the variation in outcome variables, even when accounting for other polysomnography features. CONCLUSIONS: Changes in the hemodynamic response of DLPFC may be a potential mechanism of executive dysfunction in OSA patients. And the right frontal polar region may be significant in assessing depressive symptoms in patients with OSA.

Identification of Osteosarcopenia by High-Resolution Peripheral Quantitative Computed Tomography.

Osteosarcopenia is a prevalent geriatric disease with a significantly increased risk of adverse outcomes than osteoporosis or sarcopenia alone. Identification of older adults with osteosarcopenia using High-Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) could allow better clinical decision making. This study aimed to explore the feasibility of HR-pQCT to differentiate osteoporosis, sarcopenia, and osteosarcopenia in older adults, with a primary outcome to derive a model to distinguish older adults with osteosarcopenia from those with low bone mineral density only, and to examine important HR-pQCT parameters associated with osteosarcopenia. This was a cross-sectional study involving 628 community-dwelling Chinese adults aged ≥ 40. Subjects were assessed by dual energy X-ray absorptiometry (DXA) for osteopenia/osteoporosis and sarcopenia using the Asian Working Group for Sarcopenia definition; then grouped into healthy, osteopenia/osteoporosis, sarcopenia, and osteosarcopenia groups. A series of regression analyses and other statistical tests were performed to derive the model. HR-pQCT showed the ability to discriminate older adults with osteosarcopenia from those with osteopenia/osteoporosis only. Cross-validation of our derived model correctly classified 77.0% of the cases with good diagnostic power and showed a sensitivity of 76.0% and specificity of 77.6% (Youden index = 0.54; AUC = 0.79, p < 0.001). Analysis showed trabecular volumetric bone density and cortical periosteal perimeter were important and sensitive parameters in discriminating osteosarcopenia from osteopenia/osteoporosis subjects. These findings demonstrated that HR-pQCT is a viable and effective screening method for differentiating osteosarcopenia from low bone mineral density alone without the need to carry out multiple assessments for osteosarcopenia, especially for case-finding purposes. This could facilitate the decision of a follow-up and the management of these frail older adults to ensure they receive timely therapeutic interventions to minimise the associated risks.

Effects of 5-Aminolevulinic Acid Supplementation on Gas Production, Fermentation Characteristics, and Bacterial Community Profiles In Vitro.

To investigate the effect of 5-aminolevulinic acid (5-ALA) on in vitro rumen gas production, fermentation characteristics, and bacterial community profiles, five levels of 5-ALA (0, 100, 500, 1000, and 5000 mg/kg DM) were supplemented into a total mixed ration (concentrate/forage = 40:60) as substrate in an in vitro experiment. Results showed that as the supplementation level of 5-ALA increased, asymptotic gas production (b) decreased linearly and quadratically (p < 0.01) while the dry matter degradation rate increased quadratically (p < 0.01). Meanwhile, the propionate concentration of 72 h incubation fluid increased linearly (p = 0.03) and pH value increased linearly and quadratically (p < 0.01), while the concentrations of butyrate, isobutyrate, valerate, isovalerate, and NH3-N and the ratio of acetate/propionate (A/P) decreased linearly and quadratically (p < 0.05). There was no significant difference in any alpha diversity indices of bacterial communities among the various 5-ALA levels (p < 0.05). PCoA and PERMANOVA analysis revealed that the bacterial profiles showed a statistical difference between the treatment 5-ALA at 1000 mg/kg DM and the other levels except for 5000 mg/kg DM (p < 0.05). Taxonomic classification revealed a total of 18 and 173 bacterial taxa at the phylum and genus level with relative abundances higher than 0.01% in at least half of the samples, respectively. LEfse analysis revealed that 19 bacterial taxa were affected by 5-ALA levels. Correlation analysis showed that Actinobacteriota was positively correlated with the gas production parameter b, the ratio of A/P, and the concentration of butyrate, isovalerate, and NH3-N (p < 0.05) and negatively correlated with pH (p < 0.05). WPS-2 exhibited a negative correlation with the gas production parameter b, the ratio of A/P, and the concentration of butyrate, valerate, isobutyrate, isovalerate, and NH3-N (p < 0.05), along with a weaker positive correlation with pH (p = 0.04). The Bacteroidales BS11 gut group was negatively correlated with the concentration of propionate but positively correlated with gas production parameter b and the concentration of butyrate and NH3-N (p < 0.05). The Lachnospiraceae NK3A20 group was found to have a positive correlation with gas production parameter b, the ratio of A/P, and the concentration of butyrate, isobutyrate, isovalerate, valerate, total VFA, and NH3-N (p < 0.05), but a highly negative correlation with pH (p < 0.01). Differential metabolic pathways analysis suggested that metabolic pathways related to crude protein utilization, such as L-glutamate degradation VIII (to propanoate), L-tryptophan degradation IX, and urea cycle, increased with 5-ALA levels. In summary, including 5-ALA in the diet might improve energy and protein utilization by reducing the abundance of Actinobacteriota, the Bacteroidales BS11 gut group, the Lachnospiraceae NK3A20 group, and certain pathogenic bacteria and increasing the abundance of WPS-2.

Integrated physio-biochemistry and RNA-seq revealed the mechanism underlying biochar-mediated alleviation of compound heavy metals (Cd, Pb, As) toxicity in cotton.

Biochar has been recognised as an efficacious amendment for the remediation of compound heavy metal contamination in soil. However, the molecular mechanism of biochar-mediated tolerance to compound heavy metal toxicity in cotton is unknown. The objective of this research was to investigate the positive impact of biochar (10 g·kg-1) on reducing damage caused by compound heavy metals (Cd, Pb, and As) in cotton (Gossypium hirsutum L.). The results revealed that biochar reduced Cd concentrations by 24.9 % (roots), and decreased Pb concentrations by 37.1 % (roots) and 59.53 % (stems). Biochar maintained ionic homoeostasis by regulating the expression of metal transporter proteins such as ABC, HIPP, NRAMP3, PCR, and ZIP, and genes related to the carbon skeleton and plasma membrane. Biochar also downregulated genes related to photosynthesis, thereby increasing photosynthesis. Biochar re-established redox homoeostasis in cotton by activating signal transduction, which regulated the activity of the enzymes POD, SOD, and CAT activity; and the expression of related genes. This research revealed the molecular mechanism by which biochar confers resistance to the harmful effects of compound heavy metal toxicity in cotton. The application of biochar as a soil amendment to neutralise the toxicity of compound heavy metals is recommended for cash crop production.

Association between clinical features and decreased degree centrality and variability in dynamic functional connectivity in the obsessive-compulsive disorder.

Neuroimaging studies have indicated widespread brain structural and functional disruptions in patients with obsessive-compulsive disorder (OCD). However, the underlying mechanism of these changes remains unclear. A total of 45 patients with OCD and 42 healthy controls (HC) were enrolled. The study investigated local degree centrality (DC) abnormalities and employed abnormal regions of DC as seeds to investigate variability in dynamic functional connectivity (dFC) in the whole brain using a sliding window approach to analyze resting-state functional magnetic resonance imaging. The relationship between abnormal DC and dFC as well as the clinical features of OCD were examined using correlation analysis. Our findings suggested decreased DC in the bilateral thalamus, bilateral precuneus, and bilateral cuneus in OCD patients and a nominally negative correlation between the DC value in the thalamus and illness severity measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). In addition, seed-based dFC analysis showed that compared to measurements in the HC, the patients had decreased dFC variability between the left thalamus and the left cuneus and right lingual gyrus, and between the bilateral cuneus and bilateral postcentral gyrus, and a nominally positive correlation between the duration of illness and dFC variability between the left cuneus and left postcentral gyrus. These results indicated that OCD patients had decreased hub importance in the bilateral thalamus and cuneus throughout the entire brain. This reduction was associated with impaired coupling with dynamic function in the visual cortex and sensorimotor network and provided novel insights into the neurophysiological mechanisms underlying OCD.