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Adult neurogenesis plays a crucial role in cognitive function and mood regulation, while aberrant adult neurogenesis contributes to various neurological and psychiatric diseases. With a better understanding of the significance of adult neurogenesis, the demand for improving adult neurogenesis is increasing. More and more research has shown that traditional Chinese medicine (TCM), including TCM prescriptions (TCMPs), Chinese herbal medicine, and bioactive components, has unique advantages in treating neurological and psychiatric diseases by regulating adult neurogenesis at various stages, including proliferation, differentiation, and maturation. In this review, we summarize the progress of TCM in improving adult neurogenesis and the key possible mechanisms by which TCM may benefit it. Finally, we suggest the possible strategies of TCM to improve adult neurogenesis in the treatment of neuropsychiatric disorders.
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Tamoxifen (TAM) is an accredited drug used for treatment and prevention of breast cancer. Due to the long-term taking and the trend for women to delay childbearing, inadvertent conception occasionally occurs during TAM treatment. To explore the effects of TAM on a fetus, pregnant mice at gestation day 16.5 were orally administrated with different concentrations of TAM. Molecular biology techniques were used to analyze the effects of TAM on primordial follicle assembly of female offspring and the mechanism. It was found that maternal TAM exposure affected primordial follicle assembly and damaged the ovarian reserve in 3 dpp offspring. Up to 21 dpp, the follicular development had not recovered, with significantly decreased antral follicles and decreased total follicle number after maternal TAM exposure. Cell proliferation was significantly inhibited; however, the cell apoptosis was induced by maternal TAM exposure. Epigenetic regulation was also involved in the process of TAM induced abnormal primordial follicle assembly. The changed levels of H3K4me3, H3K9me3, and H3K27me3 presented the function of histone methylation in the regulation of the effects of maternal TAM exposure on the reproduction of female offspring. Moreover, the changed level of RNA m6A modification and the changed expression of genes related to transmethylation and demethylation proved the role of m6A in the process. Maternal TAM exposure led to abnormal primordial follicle assembly and follicular development by affecting cell proliferation, cell apoptosis, and epigenetics.
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OBJECTIVE: This study compared the clinical effects of two different lipid emulsions in premature infants with gestational age < 32 weeks (VPI) or birth weight < 1500 g (VLBWI) to provide an evidence-based medicine basis for optimizing intravenous lipid emulsion. METHODS: This was a prospective multicenter randomized controlled study. A total of 465 VPIs or VLBWIs, admitted to the neonatal intensive care unit of five tertiary hospitals in China from March 1, 2021 to December 31, 2021, were recruited. All subjects were randomly allocated into two groups, namely, medium-chain triglycerides/long-chain triglycerides (MCT/LCT) group (n = 231) and soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) group (n = 234). Clinical features, biochemical indexes, nutrition support therapy, and complications were analyzed and compared between the two groups. RESULTS: No significant differences were found in perinatal data, hospitalization, parenteral and enteral nutrition support between the two groups (P > 0.05). Compared with the MCT/LCT group, the incidence of neonates with a peak value of total bilirubin (TB) > 5 mg/dL (84/231 [36.4% vs. 60/234 [25.6%]), a peak value of direct bilirubin (DB) ≥ 2 mg/dL (26/231 [11.3% vs. 14/234 [6.0%]), a peak value of alkaline phosphatase (ALP) > 900 IU/L (17/231 [7.4% vs. 7/234 [3.0%]), and a peak value of triglycerides (TG) > 3.4 mmol/L (13/231 [5.6% vs. 4/234[1.7%]]) were lower in the SMOF group (P < 0.05). Univariate analysis showed that in the subgroup analysis of < 28 weeks, the incidence of parenteral nutrition-associated cholestasis (PNAC) and metabolic bone disease of prematurity (MBDP) were lower in the SMOF group (P = 0.043 and 0.029, respectively), whereas no significant differences were present in the incidence of PNAC and MBDP between the two groups at > 28 weeks group (P = 0.177 and 0.991, respectively). Multivariate logistic regression analysis revealed that the incidence of PNAC (aRR: 0.38, 95% confidence interval [CI]: 0.20-0.70, P = 0.002) and MBDP (aRR: 0.12, 95% CI: 0.19-0.81, P = 0.029) in the SMOF group were lower than that in the MCT/LCT group. In addition, no significant differences were recorded in the incidence of patent ductus arteriosus, feeding intolerance, necrotizing enterocolitis (Bell's stage ≥ 2), late-onset sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity and extrauterine growth retardation between the two groups (P > 0.05). CONCLUSIONS: The application of mixed oil emulsion in VPI or VLBWI can reduce the risk of plasma TB > 5 mg/dL, DB ≥ 2 mg/dL, ALP > 900 IU/L, and TG > 3.4 mmol/L during hospitalization. SMOF has better lipid tolerance, reduces the incidence of PNAC and MBDP, and exerts more benefits in preterm infants with gestational age < 28 weeks.
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Tumor recurrence is one of the major life-threatening complications after liver transplantation for liver cancer. In addition to the common mechanisms underlying tumor recurrence, another unavoidable problem is that the immunosuppressive therapeutic regimen after transplantation could promote tumor recurrence and metastasis. Transplant oncology is an emerging field that addresses oncological challenges in transplantation. In this context, a comprehensive therapeutic management approach is required to balance the anti-tumor treatment and immunosuppressive status of recipients. Double-negative T cells (DNTs) are a cluster of heterogeneous cells mainly consisting of two subsets stratified by T cell receptor (TCR) type. Among them, TCRαß+ DNTs are considered to induce immune suppression in immune-mediated diseases, while TCRγδ+ DNTs are widely recognized as tumor killers. As a composite cell therapy, healthy donor-derived DNTs can be propagated to therapeutic numbers in vitro and applied for the treatment of several malignancies without impairing normal tissues or being rejected by the host. In this work, we summarized the biological characteristics and functions of DNTs in oncology, immunology, and transplantation. Based on the multiple roles of DNTs, we propose that a new balance could be achieved in liver transplant oncology using them as an off-the-shelf adoptive cell therapy (ACT).
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Imunoterapia Adotiva , Linfócitos T , Humanos , Recidiva Local de Neoplasia , Transplante Homólogo , Terapia Baseada em Transplante de Células e TecidosRESUMO
BACKGROUND: Cattle (Bos taurus) are a major large livestock, however, compared with other species, the transcriptional specificity of bovine oocyte development has not been emphasised. RESULTS: To reveal the unique transcriptional signatures of bovine oocyte development, we used integrated multispecies comparative analysis and weighted gene co-expression network analysis (WGCNA) to perform bioinformatic analysis of the germinal follicle (GV) and second meiosis (MII) gene expression profile from cattle, sheep, pigs and mice. We found that the expression levels of most genes were down-regulated from GV to MII in all species. Next, the multispecies comparative analysis showed more genes involved in the regulation of cAMP signalling during bovine oocyte development. Moreover, the green module identified by WGCNA was closely related to bovine oocyte development. Finally, integrated multispecies comparative analysis and WGCNA picked up 61 bovine-specific signature genes that participate in metabolic regulation and steroid hormone biosynthesis. CONCLUSION: In a short, this study provides new insights into the regulation of cattle oocyte development from a cross-species comparison.
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Oócitos , Transcriptoma , Bovinos , Animais , Camundongos , Ovinos/genética , Suínos , Oócitos/metabolismo , Técnicas de Maturação in Vitro de Oócitos/veterinária , Oogênese/genética , Perfilação da Expressão GênicaRESUMO
Type 2 diabetes (T2D) is a major health and economic burden worldwide. Despite the availability of multiple drugs for short-term management, sustained remission of T2D is currently not achievable pharmacologically. Intracerebroventricular administration of fibroblast growth factor 1 (icvFGF1) induces sustained remission in T2D rodents, propelling intense research efforts to understand its mechanism of action. Whether other FGFs possess similar therapeutic benefits is currently unknown. Here, we show that icvFGF4 also elicits a sustained antidiabetic effect in both male db/db mice and diet-induced obese mice by activating FGF receptor 1 (FGFR1) expressed in glucose-sensing neurons within the mediobasal hypothalamus. Specifically, FGF4 excites glucose-excited (GE) neurons while inhibiting glucose-inhibited (GI) neurons. Moreover, icvFGF4 restores the percentage of GI neurons in db/db mice. Importantly, intranasal delivery of FGF4 alleviates hyperglycemia in db/db mice, paving the way for non-invasive therapy. We conclude that icvFGF4 holds significant therapeutic potential for achieving sustained remission of T2D.
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The current methods to control RNA functions in living conditions are limited. The new RNA-controlling strategy presented in this study involves utilizing 5-formylcytidine (f5C)-directed base manipulation. This study shows that malononitrile and pyridine boranes can effectively manipulate the folding, small molecule binding, and enzyme recognition of f5C-bearing RNAs. We further demonstrate the efficiency of f5C-directed reactions in controlling two different clustered regularly interspaced short palindromic repeat (CRISPR) systems. Although further studies are needed to optimize the efficiency of these reactions in vivo, this small molecule-based approach presents exciting new opportunities for regulating CRISPR-based gene expression and other applications.
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Hypoxia-induced adenosine creates an immunosuppressive tumor microenvironment (TME) and dampens the efficacy of immune checkpoint inhibitors (ICIs). We found that hypoxia-inducible factor 1 (HIF-1) orchestrates adenosine efflux through two steps in hepatocellular carcinoma (HCC). First, HIF-1 activates transcriptional repressor MXI1, which inhibits adenosine kinase (ADK), resulting in the failure of adenosine phosphorylation to adenosine monophosphate. This leads to adenosine accumulation in hypoxic cancer cells. Second, HIF-1 transcriptionally activates equilibrative nucleoside transporter 4, pumping adenosine into the interstitial space of HCC, elevating extracellular adenosine levels. Multiple in vitro assays demonstrated the immunosuppressive role of adenosine on T cells and myeloid cells. Knockout of ADK in vivo skewed intratumoral immune cells to protumorigenic and promoted tumor progression. Therapeutically, combination treatment of adenosine receptor antagonists and anti-PD-1 prolonged survival of HCC-bearing mice. We illustrated the dual role of hypoxia in establishing an adenosine-mediated immunosuppressive TME and offered a potential therapeutic approach that synergizes with ICIs in HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Camundongos Knockout , Hipóxia/metabolismo , Adenosina/metabolismo , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
PURPOSE: To identify parameters and measurement methods of exercise therapy adherence, as well as barriers and facilitators affecting adherence among children and adolescents with juvenile idiopathic arthritis (JIA). METHODS: Studies were eligible for inclusion if patients were 0-18 years of age, had JIA, and the focus of the research was on exercise therapy patterns, measurement/parameters of exercise adherence, and barriers/facilitators for exercise adherence. Two reviewers independently identified and categorized the barriers and facilitators to exercise therapy adherence using the International Classification of Functioning, Disability, and Health (ICF). RESULTS: Twenty articles were included in this review. Among patients with JIA, 29%-99% adhered to exercise therapy. The most commonly measured parameters of adherence were session completion and behavior component, with a self-report log serving as the most common means of assessment. Time pressure, symptoms related to JIA, lack of enjoyment, and insufficient motivation were the main barriers. Facilitators were commonly identified as adequate motivation, effective symptoms management, and social support. CONCLUSIONS: Future interventions should consider the identified factors to promote exercise engagement in children and adolescents with JIA. Strategies for promoting exercise adherence in children and adolescents with JIA is needed.
Despite its potential as an effective means of improving health and function in patients with juvenile idiopathic arthritis (JIA), the level of exercise participation in this population is not ideal.Future interventions should focus on improving personal factors associated with exercise therapy adherence, such as motivation.To facilitate the participation in the exercise of children and adolescents with JIA, supportive exercise environments should be provided.
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The purpose of this study was to explore and compare the relationship among serum testosterone, systemic inflammatory response index (SIRI), lymphocyte-to-monocyte ratio (LMR) neutrophil-lymphocyte ratio (NLR), and carotid atherosclerosis in middle-aged and elderly men of Han nationality in the real world. With reference to the inclusion criteria, 89 middle-aged and elderly Han male patients were finally selected. Local weighted regression (LOESS) and multivariate logistic regression models were used to explore the independent correlation between serum testosterone, new inflammatory markers, and atherosclerosis. The diagnostic value of related indexes was evaluated by the receiver working curve characteristic curve (ROC), and the best critical value of testosterone and related inflammatory indexes was discussed. In the LOESS model, bioavailable testosterone (BT), free testosterone (FT), total testosterone (TT) and SIRI, NLR, LMR, and atherosclerosis were significantly correlated. After adjusting for confounding factors, BT, FT, TT, and LMR were negatively correlated with atherosclerosis (odds ratio [OR] < 1, p < .05), and SIRI and NLR were positively associated with atherosclerosis (OR > 1, p < .05). According to the ROC curve results, the area under the curve (AUG) of BT is 0.870, and the optimal threshold point is 4.875. The AUG of SIRI is 0.864, and the best threshold point is 0.769. Low testosterone and high inflammatory levels are closely related to atherosclerosis. Testosterone (TT, FT, and BT) and new inflammatory markers, SIRI, NLR, and LMR, are associated with carotid atherosclerosis in middle-aged and elderly men.
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Aterosclerose , Doenças das Artérias Carótidas , Idoso , Pessoa de Meia-Idade , Humanos , Masculino , Testosterona , Neutrófilos , Monócitos , População do Leste Asiático , Estudos Retrospectivos , LinfócitosRESUMO
OBJECTIVE: Cardiorenal syndrome type 4 (CRS4) is a complication of chronic kidney disease. Panax notoginseng saponins (PNS) have been confirmed to be efficient in cardiovascular diseases. Our study aimed to explore the therapeutic role and mechanism of PNS in CRS4. METHODS: CRS4 model rats and hypoxia-induced cardiomyocytes were treated with PNS, with and without pyroptosis inhibitor VX765 and ANRIL overexpression plasmids. Cardiac function and cardiorenal function biomarkers levels were measured by echocardiography and ELISA, respectively. Cardiac fibrosis was detected by Masson staining. Cell viability was determined by cell counting kit-8 and flow cytometry. Expression of fibrosis-related genes (COL-I, COL-III, TGF-ß, α-SMA) and ANRIL was examined using RT-qPCR. Pyroptosis-related protein levels of NLRP3, ASC, IL-1ß, TGF-ß1, GSDMD-N, and caspase-1 were measured by western blotting or immunofluorescence staining. RESULTS: PNS improved cardiac function, and inhibited cardiac fibrosis and pyroptosis in a dose-dependent manner in model rats and injured H9c2 cells (p < 0.01). The expression of fibrosis-related genes (COL-I, COL-III, TGF-ß, α-SMA) and pyroptosis-related proteins (NLRP3, ASC, IL-1ß, TGF-ß1, GSDMD-N, and caspase-1) was inhibited by PNS in injured cardiac tissues and cells (p < 0.01). Additionally, ANRIL was upregulated in model rats and injured cells, but PNS reduced its expression in a dose-dependent manner (p < 0.05). Additionally, the inhibitory effect of PNS on pyroptosis in injured H9c2 cells was enhanced by VX765 and reversed by ANRIL overexpression, respectively (p < 0.05). CONCLUSION: PNS inhibits pyroptosis by downregulating lncRNA-ANRIL in CRS4.
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The recovery of volatile fatty acids (VFAs) through anaerobic fermentation (AF) is usually restricted by the poor biodegradability of waste activated sludge (WAS). This study proposed a novel strategy, i.e. peroxymonosulfate (PMS) activated by Fe-loaded sodium alginate hydrogel beads (Fe-SA), to enhance AF performance. Experimental results demonstrated that the as-synthesized Fe-SA and PMS co-pretreatment synergistically enhanced WAS solubilization and VFAs production. The maximal VFAs yield of 2013 mg COD/L was achieved at the Fe-SA dosage of 4.0 mM/g TSS, which was 93.7% higher than that with sole PMS addition and 8.82 times higher than that of the control. Mechanistic studies elucidated that the generation of reactive radicals such as SO4â¢- and â¢OH from PMS was greatly induced by Fe-SA, which contributed to WAS disintegration and degradation of refractory compounds. Additionally, analysis of the key enzyme activities indicated that the Fe-SA could strengthen biological hydrolysis and acidogenesis of sludge during AF. Microbial analysis illustrated that Fe-SA evidently improved the abundances of fermentative microorganisms as well as functional gene expression via creating a favorable environment for microbial growth. This study demonstrated the applicable potential of Fe-SA hydrogel beads activating PMS for VFAs production and provides an important reference for developing advanced oxidation processes-based application in AF.
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BACKGROUND: Testis is the only organ supporting sperm production and with the largest number of proteins and tissue-specific proteins in animals. In our previous studies, we have found that knockdown of ocnus (ocn), a testis-specific gene, resulted in much smaller testis with no germ cells in Drosophila melanogaster. However, the molecular consequences of ocn knockdown in fly testes are unknown. RESULTS: In this study, through iTRAQ quantitative proteomics sequencing, 606 proteins were identified from fly abdomens as having a significant and at least a 1.5-fold change in expression after ocn knockdown in fly testes, of which 85 were up-regulated and 521 were down-regulated. Among the differential expressed proteins (DEPs), apart from those proteins involved in spermatogenesis, the others extensively affected biological processes of generation of precursor metabolites and energy, metabolic process, and mitochondrial transport. Protein-protein interaction (PPI) analyses of DEPs showed that several kinases and/or phosphatases interacted with Ocn. Re-analyses of the transcriptome revealed 150 differential expressed genes (DEGs) appeared in the DEPs, and their changing trends in expressions after ocn knockdown were consistent. Many common down-regulated DEGs and DEPs were testis-specific or highly expressed in the testis of D. melanogaster. Quantitative RT-PCR (qRT-PCR) confirmed 12 genes appeared in both DEGs and DEPs were significantly down-regulated after ocn knockdown in fly testes. Furthermore, 153 differentially expressed phosphoproteins (DEPPs), including 72 up-regulated and 94 down-regulated phosphorylated proteins were also identified (13 phosphoproteins appeared in both up- and down-regulated groups due to having multiple phosphorylation sites). In addition to those DEPPs associated with spermatogenesis, the other DEPPs were enriched in actin filament-based process, protein folding, and mesoderm development. Some DEPs and DEPPs were involved in Notch, JAK/STAT, and cell death pathways. CONCLUSIONS: Given the drastic effect of the ocn knockdown on tissue development and testis cells composition, the differences in protein abundance in the ocn knockdown flies might not necessarily be the direct result of differential gene regulation due to the inactivation of ocn. Nevertheless, our results suggest that the expression of ocn is essential for Drosophila testis development and that its down-regulation disturbs key signaling pathways related to cell survival and differentiation. These DEPs and DEPPs identified may provide significant candidate set for future studies on the mechanism of male reproduction of animals, including humans.
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Drosophila , Testículo , Humanos , Animais , Masculino , Testículo/metabolismo , Drosophila melanogaster/genética , Proteômica/métodos , Sêmen , Fosfoproteínas/genética , Fosfoproteínas/metabolismoRESUMO
BACKGROUND: It is proposed that the development of parenteral nutrition-associated cholestasis (PNAC) was significantly associated with preterm birth, low birth weight, infection, etc.; however, the etiology and pathogenesis of PNAC are not fully understood. Most of the studies examining PNAC-associated risk factors were single-center studies with relatively small sample sizes. OBJECTIVE: To analyze the risk factors associated with PNAC in preterm infants in China. METHODS: This is a retrospective multicenter observational study. Clinical data on the effect of multiple oil-fat emulsions (soybean oil-medium chain triglycerides-olive oil-fish oil, SMOF) in preterm infants were collected from a prospective multicenter randomized controlled study. A secondary analysis was performed in which preterm infants were divided into the PNAC group and the non-PNAC group based on the PNAC status. RESULTS: A total of 465 cases very preterm infants or very low birth weight infants were included in the study in which 81 cases were assigned to the PNAC group and 384 cases were assigned to the non-PNAC group. The PNAC group had a lower mean gestational age, lower mean birth weight, longer duration of invasive and non-invasive mechanical ventilation, a longer duration oxygen support, and longer hospital stay (P < 0.001 for all). The PNAC group had higher respiratory distress syndrome, hemodynamically significant patent ductus arteriosus, necrotizing enterocolitis (NEC) with stage II or higher, surgically treated NEC, late-onset sepsis, metabolic bone disease, and extrauterine growth retardation (EUGR) compared to the non-PNAC group (P < 0.05 for all). In contrast with the non-PNAC group, the PNAC group received a higher maximum dose of amino acids and fat emulsion, more medium/long-chain fatty emulsion, less SMOF, had a longer duration of parenteral nutrition, lower rates of breastfeeding, higher incidence of feeding intolerance (FI), more accumulated days to achieve total enteral nutrition, less accumulated days of total calories up to standard 110 kcal/kg/day and slower velocity of weight growth (P < 0.05 for all). Logistic regression analysis indicated that the maximum dose of amino acids (OR, 5.352; 95% CI, 2.355 to 12.161), EUGR (OR, 2.396; 95% CI, 1.255 to 4.572), FI (OR, 2.581; 95% CI, 1.395 to 4.775), surgically treated NEC (OR, 11.300; 95% CI, 2.127 ~ 60.035), and longer total hospital stay (OR, 1.030; 95% CI, 1.014 to 1.046) were independent risk factors for the development of PNAC. SMOF (OR, 0.358; 95% CI, 0.193 to 0.663) and breastfeeding (OR, 0.297; 95% CI, 0.157 to 0.559) were protective factors for PNAC. CONCLUSIONS: PNAC can be reduced by optimizing the management of enteral and parenteral nutrition and reducing gastrointestinal comorbidities in preterm infants.
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Colestase , Nascimento Prematuro , Feminino , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Emulsões/química , Peso ao Nascer , Estudos Prospectivos , Nascimento Prematuro/etiologia , Colestase/etiologia , Colestase/epidemiologia , Nutrição Parenteral/efeitos adversos , Recém-Nascido de muito Baixo Peso , Aminoácidos , Fatores de RiscoRESUMO
Silver nanoparticles (AgNPs) possess anti-inflammatory activities and have been widely deployed for promoting tissue repair. Here we explored the efficacy of AgNPs on functional recovery after spinal cord injury (SCI). Our data indicated that, in a SCI rat model, local AgNPs delivery could significantly recover locomotor function and exert neuroprotection through reducing of pro-inflammatory M1 survival. Furthermore, in comparison with Raw 264.7-derived M0 and M2, a higher level of AgNPs uptake and more pronounced cytotoxicity were detected in M1. RNA-seq analysis revealed the apoptotic genes in M1 were upregulated by AgNPs, whereas in M0 and M2, pro-apoptotic genes were downregulated and PI3k-Akt pathway signaling pathway was upregulated. Moreover, AgNPs treatment preferentially reduced cell viability of human monocyte-derived M1 comparing to M2, supporting its effect on M1 in human. Overall, our findings reveal AgNPs could suppress M1 activity and imply its therapeutic potential in promoting post-SCI motor recovery.
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Designing and synthesizing cuprous halide phosphors unifying efficient low-energy emission and a broad excitation band is still a great challenge. Herein, by rational component design, three novel Cu(i)-based metal halides, DPCu4X6 [DP = (C6H10N2)4(H2PO2)6; X = Cl, Br, I], were synthesized by reacting p-phenylenediamine with cuprous halide (CuX), and they show similar structures, consisting of isolated [Cu4X6]2- units separated by organic layers. Photophysical studies uncover that the highly localized excitons and rigid environment give rise to highly efficient yellow-orange photoluminescence in all compounds with the excitation band spanning from 240 to 450 nm. The bright PL in DPCu4X6 (X = Cl, Br) originates from self-trapped excitons due to the strong electron-phonon coupling. Intriguingly, DPCu4I6 features a dual-band emissive characteristic, attributed to the synergistic effect of halide/metal-to-ligand charge-transfer (X/MLCT) and triplet cluster-centered (3CC) excited states. Benefiting from the broadband excitation, a high-performance white-light emitting diode (WLED) with a high color rendering index of 85.1 was achieved using single-component DPCu4I6 phosphor. This work not only unveils the role of halogens in the photophysical processes of cuprous halides, but also provides new design principles for high-performance single-component WLEDs.
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Huoluo Xiaoling Pellet (HXP), a Chinese patent medicine, is commonly administered for the treatment of treat ischemic strokes. MCPIP1, an inducible suppressor of the inflammatory response, is a regulator of microglial M2 polarization. This study aimed to explore whether HXP can promote microglial M2 polarization by upregulating MCPIP1 expression, consequently mitigating cerebral ischemic injury. Our study involved 85 Sprague-Dawley rats (weighing 250-280 g). We established middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation-reoxygenation (OGD/R) models with MCPIP1 knockdown to assess the effects of HXP on ischemic strokes. Our findings show that HXP reduced brain water content, improved neurological function, and inhibited the expression of inflammatory factors in the brain tissues of MCAO rats. The neuroprotective effects of HXP on cerebral ischemic injuries were compromised by MCPIP1 knockdown. Immunofluorescence results indicated that the expression of microglia marker Iba1 and M2 phenotypic marker CD206 was upregulated in MCAO rats and OGD/R-treated microglia. Administration of HXP significantly reduced Iba1 expression and facilitated CD206 expression, an effect that was counteracted by sh-MCPIP1 transfection. Western blotting revealed that HXP treatment augmented the expression of MCPIP1, microglial M2 marker proteins (CD206 and Arg1), and PPARγ, while reducing the expression of microglial M1 marker proteins (CD16 and iNOS) in MCAO rats and OGD/R-induced microglia. MCPIP1 knockdown suppressed HXP-mediated upregulation of MCPIP1, CD206, Arg1, and PPARγ, as well as the downregulation of CD16 and iNOS. Our findings suggest that HXP primarily ameliorates ischemic stroke through the upregulation of MCPIP1, which in turn induces microglial M2 polarization.
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Purpose: This study aims to construct a machine learning model that can recognize preoperative, intraoperative, and postoperative high-risk indicators and predict the onset of venous thromboembolism (VTE) in patients. Patients and Methods: A total of 1239 patients diagnosed with gastric cancer were enrolled in this retrospective study, among whom 107 patients developed VTE after surgery. We collected 42 characteristic variables of gastric cancer patients from the database of Wuxi People's Hospital and Wuxi Second People's Hospital between 2010 and 2020, including patients' demographic characteristics, chronic medical history, laboratory test characteristics, surgical information, and patients' postoperative conditions. Four machine learning algorithms, namely, extreme gradient boosting (XGBoost), random forest (RF), support vector machine (SVM), and k-nearest neighbor (KNN), were employed to develop predictive models. We also utilized Shapley additive explanation (SHAP) for model interpretation and evaluated the models using k-fold cross-validation, receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and external validation metrics. Results: The XGBoost algorithm demonstrated superior performance compared to the other three prediction models. The area under the curve (AUC) value for XGBoost was 0.989 in the training set and 0.912 in the validation set, indicating high prediction accuracy. Furthermore, the AUC value of the external validation set was 0.85, signifying good extrapolation of the XGBoost prediction model. The results of SHAP analysis revealed that several factors, including higher body mass index (BMI), history of adjuvant radiotherapy and chemotherapy, T-stage of the tumor, lymph node metastasis, central venous catheter use, high intraoperative bleeding, and long operative time, were significantly associated with postoperative VTE. Conclusion: The machine learning algorithm XGBoost derived from this study enables the development of a predictive model for postoperative VTE in patients after radical gastrectomy, thereby assisting clinicians in making informed clinical decisions.
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Global climate change and revegetation programs have significantly changed the ecological quality (EQ) in the Chinese mainland after 1999. Monitoring and assessing the changes in the regional EQ and analyzing their drivers are crucial for ensuring ecological restoration and rehabilitation. However, it is challenging to carry out a long-term and large-scale quantitative assessment of the EQ of a region based on traditional field investigations and experiment methods alone; notably, in previous studies, the effects of carbon and water cycles and human activities on the variations in EQ have not been studied comprehensively. Therefore, in addition to remote sensing data and principal component analysis, we used the remote sensing-based ecological index (RSEI), to assess the EQ changes in the Chinese mainland during 2000-2021. Additionally, we also analyzed the impacts of carbon and water cycles and anthropological activities on the changes in the RSEI. The main conclusions of this study were: since the beginning of the 21st century, we observed a fluctuating upward trend in the EQ changes in the Chinese mainland and eight climatic regions. From 2000 to 2021, in terms of the EQ, North China (NN) portrayed the highest increase rate (2.02 × 10-3 year-1, P < 0.05). There was a breaking point in 2011, the EQ in the region experienced a change, from a downward trend to an upward one. Northwest China, Northeast China, and NN portrayed an overall significant increasing trend in the RSEI, whereas the southwest part of the Southwest Yungui Plateau (YG) and a part of the plain region of the Changjiang (Yangtze) River (CJ) river region portrayed a significant decreasing trend in the EQ. Overall, the carbon and water cycles and human activities played a pivotal role in determining the spatial patterns and trends of the EQ in the Chinese mainland. In particular, the self-calibrating Palmer Drought Severity Index, actual evapotranspiration (AET), gross primary productivity (GPP), and soil water content (Soil_w) were identified as the key drivers of the RSEI. In the central and western Qinghai-Tibetan Plateau (QZ) and the northwest region of NW, the changes in RSEI were dominated by AET; however, in central NN, southeastern QZ, northern YG, and central NE, the changes were driven by GPP, and in the southeast region of NW, south region of NE, northern region of NN, middle YG region, and a part of the middle CJ region, the changes were driven by Soil_w. The population-density-related change in the RSEI was positive in the northern regions (NN and NW) but negative in the southern regions (SE), whereas the RSEI change related to ecosystem services was positive in the NE, NW, QZ, and YG regions. These results are beneficial for the adaptive management and protection of the environment and the realization of green and sustainable developmental strategies in the Chinese mainland.