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JOURNAL/nrgr/04.03/01300535-202504000-00027/figure1/v/2024-07-06T104127Z/r/image-tiff Cardiac arrest can lead to severe neurological impairment as a result of inflammation, mitochondrial dysfunction, and post-cardiopulmonary resuscitation neurological damage. Hypoxic preconditioning has been shown to improve migration and survival of bone marrow-derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest, but the specific mechanisms by which hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown. To this end, we established an in vitro co-culture model of bone marrow-derived mesenchymal stem cells and oxygen-glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis, possibly through inhibition of the MAPK and nuclear factor κB pathways. Subsequently, we transplanted hypoxia-preconditioned bone marrow-derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia. The results showed that hypoxia-preconditioned bone marrow-derived mesenchymal stem cells significantly reduced cardiac arrest-induced neuronal pyroptosis, oxidative stress, and mitochondrial damage, whereas knockdown of the liver isoform of phosphofructokinase in bone marrow-derived mesenchymal stem cells inhibited these effects. To conclude, hypoxia-preconditioned bone marrow-derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest, and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

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BACKGROUND: Immunotherapy presents both promises and challenges in treating hepatocellular carcinoma (HCC) due to its complex immunological microenvironment. The role of B cells, a key part of the immune system, remains uncertain in HCC. AIM: To identify B-cell-specific signatures and reveal novel immunophenotyping and therapeutic targets for HCC. METHODS: Using the Tumor Immune Single-cell Hub 2 database, we identified B-cell-related genes (BRGs) in HCC. Gene enrichment analysis was performed to explore the possible collaboration between B cells and T cells in HCC. We conducted univariate Cox regression analysis using The Cancer Genome Atlas liver HCC collection dataset to find BRGs linked to HCC prognosis. Subsequently, least absolute shrinkage and selection operator regression was utilized to develop a prognostic model with 11 BRGs. The model was validated using the International Cancer Genome Consortium dataset and GSE76427. RESULTS: The risk score derived from the prognostic model emerged as an independent prognostic factor for HCC. Analysis of the immune microenvironment and cell infiltration revealed the immune status of various risk groups, supporting the cooperation of B and T cells in suppressing HCC. The BRGs model identified new molecular subtypes of HCC, each with distinct immune characteristics. Drug sensitivity analysis identified targeted drugs effective for each HCC subtype, enabling precision therapy and guiding clinical decisions. CONCLUSION: We clarified the role of B cells in HCC and propose that the BRGs model offers promising targets for personalized immunotherapy.

Assuntos

Linfócitos B , Carcinoma Hepatocelular , Imunofenotipagem , Neoplasias Hepáticas , Microambiente Tumoral , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológico , Microambiente Tumoral/imunologia , Imunofenotipagem/métodos , Prognóstico , Linfócitos B/imunologia , Linfócitos B/efeitos dos fármacos , Imunoterapia/métodos , Biomarcadores Tumorais/genética , Masculino , Regulação Neoplásica da Expressão Gênica , Terapia de Alvo Molecular/métodos , Feminino , Linfócitos T/imunologia , Bases de Dados Genéticas , Perfilação da Expressão Gênica/métodos

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Cardiac biological pacing (BP) is one of the future directions for bradyarrhythmias intervention. Currently, cardiac pacemaker cells (PCs) used for cardiac BP are mainly derived from pluripotent stem cells (PSCs). However, the production of high-quality cardiac PCs from PSCs remains a challenge. Here, we developed a cardiac PC differentiation strategy by adopting dual PC markers and simulating the developmental route of PCs. First, two PC markers, Shox2 and Hcn4, were selected to establish Shox2:EGFP; Hcn4:mCherry mouse PSC reporter line. Then, by stepwise guiding naïve PSCs to cardiac PCs following naïve to formative pluripotency transition and manipulating signaling pathways during cardiac PCs differentiation, we designed the FSK method that increased the yield of SHOX2+; HCN4+ cells with typical PC characteristics, which was 12 and 42 folds higher than that of the embryoid body (EB) and the monolayer M10 methods respectively. In addition, the in vitro cardiac PCs differentiation trajectory was mapped by single-cell RNA sequencing (scRNA-seq), which resembled in vivo PCs development, and ZFP503 was verified as a key regulator of cardiac PCs differentiation. These PSC-derived cardiac PCs have the potential to drive advances in cardiac BP technology, help with the understanding of PCs (patho)physiology, and benefit drug discovery for PC-related diseases as well.

Assuntos

Diferenciação Celular , Miócitos Cardíacos , Células-Tronco Pluripotentes , Animais , Camundongos , Diferenciação Celular/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/citologia , Células-Tronco Pluripotentes/metabolismo , Células-Tronco Pluripotentes/citologia , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Corpos Embrioides/citologia , Corpos Embrioides/metabolismo

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Fish can use hydrodynamic stimuli, decoded by lateral line systems, to explore the surroundings. Eyeless species of the genus Sinocyclocheilus have evolved conspicuous horns on their heads, whereas the specific function of which is still unknown. Meanwhile, the eyeless cavefish exhibits more sophisticated lateral line systems and enhanced behavioral capabilities (for instance rheotaxis), compared with their eyed counterparts. Here, the influence of head horn on the hydrodynamic perception capability is investigated through computational fluid dynamics, particle image velocimetry, and a bioinspired cavefish model integrated with an artificial lateral line system. The results show strong evidence that the head horn structure can enhance the hydrodynamic perception, from aspects of multiple hydrodynamic sensory indicators. It is uncovered as that the head horn renders eyeless cavefish with stronger hydrodynamic stimuli, induced by double-stagnation points near the head, which are perceived by the strengthened lateral line systems. Furthermore, the eyeless cavefish model has ≈17% higher obstacle recognition accuracy and lower cost (time and sensor number) than eyed cavefish model is conceptually demonstrated, by incorporating with machine learning. This study provides novel insights into form-function relationships in eyeless cavefish, in addition paves the way for optimizing sensor arrangement in fish robots and underwater vehicles.

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Rheumatoid arthritis (RA) is a chronic autoimmune disease accompanied by local and systemic bone loss. FcγRs, especially FcγRIIa (hFcγRIIa), have been implicated in the pathogenesis of RA. However, the contribution of hFcγRIIa to bone loss has not been fully elucidated. In the present study, we demonstrated the double-edged sword role of hFcγRIIa on osteoclast differentiation through investigations involving hFcγRIIa-transgenic (hFcγRIIa-Tg) mice. Our findings reveal that hFcγRIIa-Tg mice, previously shown to exhibit heightened susceptibility to collagen-induced arthritis (CIA), displayed increased osteoporosis during CIA or at advanced ages (40 weeks), accompanied by heightened in vivo osteoclast differentiation. Notably, bone marrow cells from hFcγRIIa-Tg mice exhibited enhanced efficiency in differentiating into osteoclasts and bone resorption in vitro compared to wild-type mice when stimulated with receptor activators of NF-κB ligand (RANKL). Additionally, hFcγRIIa-Tg mice exhibited augmented sensitivity to RANKL-induced bone loss in vivo, highlighting the osteoclast-promoting role of hFcγRIIa. Mechanistically, bone marrow cells from hFcγRIIa-Tg mice displayed heightened Syk self-activation, leading to mTOR-pS6 pathway activation, thereby promoting RANKL-driven osteoclast differentiation. Intriguingly, while hFcγRIIa crosslinking hindered RANKL-induced osteoclast differentiation, it activated the kinase cAbl, subsequently triggering STAT5 activation and inhibiting the expression of osteoclast-associated genes. This study provides novel insights into hFcγRIIa-mediated osteoclast biology, suggesting promising therapeutic targets for managing bone remodeling disorders.

Assuntos

Reabsorção Óssea , Diferenciação Celular , Osteoclastos , Osteogênese , Receptores de IgG , Animais , Camundongos , Artrite Experimental/imunologia , Artrite Experimental/genética , Artrite Reumatoide/metabolismo , Artrite Reumatoide/imunologia , Artrite Reumatoide/genética , Reabsorção Óssea/genética , Reabsorção Óssea/metabolismo , Camundongos Transgênicos , Osteoclastos/metabolismo , Osteoporose/genética , Osteoporose/etiologia , Osteoporose/metabolismo , Ligante RANK/metabolismo , Ligante RANK/genética , Receptores de IgG/genética , Receptores de IgG/metabolismo , Transdução de Sinais

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BACKGROUND: Bacteriophage has been renewed attention as a new antibacterial agent due to the limitations of antibiotic treatment. Bacteriophages are generally thought to be highly host specific and even strain specific, but a small number of polyvalent bacteriophages have been found to infect bacteria of different genera. RESULTS: In this study, a virulent lytic bacteriophage (named Salmonella phage PSH-1) of Salmonella Enteritidis was isolated from the sewage samples of a large-scale pig farm, PSH-1 demonstrated lytic activity against four multidrug-resistant Salmonella Enteritidis isolates and Escherichia coli, and then its biological characteristics, genome and bacteriostatic ability were investigated. The results showed that the initial titer of PSH-1 was 1.15 × 1010 PFU/mL and the optimal multiplicity of infection (MOI) was 0.01, PSH-1 has stable activity in the range of pH 3.0-11.0. One-step growth curve showed that its latent period was 20 min, burst time was 80 min, and the burst was 495 particles. The whole-genome sequencing results revealed phage PSH-1 had a linear dsDNA with 48,466 bp length. The G/C content was 45.33%. Non-coding RNA genes and virulence factors were not found. Eighty- five open reading frames (ORFs) were identified after online annotation. By tests, the use of phage could succeed in controlling the artificial Salmonella contamination in milk at a range of temperatures. CONCLUSIONS: This study reports a novel Salmonella Enteritidis phage PSH-1, which has a robust lytic ability, no virulence factors, and good stability. The characterization and genomic analysis of PSH-1 will develop our understanding of phage biology and diversity and provide a potential arsenal for controlling of salmonellosis.

Assuntos

Farmacorresistência Bacteriana Múltipla , Genoma Viral , Fagos de Salmonella , Salmonella enteritidis , Esgotos , Sequenciamento Completo do Genoma , Salmonella enteritidis/virologia , Salmonella enteritidis/genética , Salmonella enteritidis/efeitos dos fármacos , Fagos de Salmonella/genética , Fagos de Salmonella/isolamento & purificação , Fagos de Salmonella/fisiologia , Fagos de Salmonella/classificação , Farmacorresistência Bacteriana Múltipla/genética , Animais , Esgotos/virologia , Esgotos/microbiologia , Suínos , Composição de Bases , Escherichia coli/virologia , Escherichia coli/genética

RESUMO

The spalt (Sal) gene family has four members (Sall1-4) in vertebrates, all of which play pivotal roles in various biological processes and diseases. However, the expression and function of SALL2 in development are still less clear. Here, we first charted SALL2 protein expression pattern during mouse embryo development by immunofluorescence, which revealed its dominant expression in the developing nervous system. With the establishment of Sall2 deficient mouse embryonic stem cells (ESCs), the in vitro neural differentiation system was leveraged to interrogate the function of SALL2, which showed impaired neural differentiation of Sall2 knockout (KO) ESCs. Furthermore, neural stem cells (NSCs) could not be derived from Sall2 KO ESCs and the generation of neural tube organoids (NTOs) was greatly inhibited in the absence of SALL2. Meanwhile, transgenic expression of E1 isoform of SALL2 restored the defects of neural differentiation in Sall2 KO ESCs. By chromatin immunoprecipitation sequencing (ChIP-seq), Tuba1a was identified as downstream target of SALL2, whose function in neural differentiation was confirmed by rescuing neural phenotypes of Sall2 KO ESCs when overexpressed. In sum, by elucidating SALL2 expression dynamics during early mouse development and mechanistically characterizing its indispensable role in neural differentiation, this study offers insights into SALL2's function in human nervous system development, associated pathologies stemming from its mutations and relevant therapeutic strategy.

Assuntos

Diferenciação Celular , Células-Tronco Embrionárias Murinas , Fatores de Transcrição , Animais , Camundongos , Células-Tronco Embrionárias Murinas/metabolismo , Células-Tronco Embrionárias Murinas/citologia , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/citologia , Neurogênese , Camundongos Knockout , Regulação da Expressão Gênica no Desenvolvimento

RESUMO

The segmentation of fundus tumors is critical for ophthalmic diagnosis and treatment, yet it presents unique challenges due to the variability in lesion size and shape. Our study introduces Fundus Tumor Segmentation Network (FTSNet), a novel segmentation network designed to address these challenges by leveraging classification results and prompt learning. Our key innovation is the multiscale feature extractor and the dynamic prompt head. Multiscale feature extractors are proficient in eliciting a spectrum of feature information from the original image across disparate scales. This proficiency is fundamental for deciphering the subtle details and patterns embedded in the image at multiple levels of granularity. Meanwhile, a dynamic prompt head is engineered to engender bespoke segmentation heads for each image, customizing the segmentation process to align with the distinctive attributes of the image under consideration. We also present the Fundus Tumor Segmentation (FTS) dataset, comprising 254 pairs of fundus images with tumor lesions and reference segmentations. Experiments demonstrate FTSNet's superior performance over existing methods, achieving a mean Intersection over Union (mIoU) of 0.8254 and mean Dice (mDice) of 0.9042. The results highlight the potential of our approach in advancing the accuracy and efficiency of fundus tumor segmentation.

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Madin-Darby canine kidney (MDCK) cells are commonly used to produce cell-based influenza vaccines. However, the role of the low-serum medium on the proliferation of MDCK cells and the propagation of the influenza virus has not been well studied. In the present study, we used 5 of 15 culture methods with different concentrations of a mixed medium and neonatal bovine serum (NBS) to determine the best culture medium. We found that a VP:M199 ratio of 1:2 (3% NBS) was suitable for culturing MDCK cells. Furthermore, the stable growth of MDCK cells and the production of the influenza virus were evaluated over long-term passaging. We found no significant difference in terms of cell growth and virus production between high and low passages of MDCK cells under low-serum culture conditions, regardless of influenza virus infection. Lastly, we performed a comparison of the transcriptomics and proteomics of MDCK cells cultured in VP:M199 = 1:2 (3% NBS) with those cultured in VP:M199 = 1:2 (5% NBS) before and after influenza virus infection. The transcriptome analysis showed that differentially expressed genes were predominantly enriched in the metabolic pathway and MAPK signaling pathway, indicating an activated state. This suggests that decreasing the concentration of serum in the medium from 5% to 3% may increase the metabolic activity of cells. Proteomics analysis showed that only a small number of differentially expressed proteins could not be enriched for analysis, indicating minimal difference in the protein levels of MDCK cells when the serum concentration in the medium was decreased from 5% to 3%. Altogether, our findings suggest that the screening and application of a low-serum medium provide a background for the development and optimization of cell-based influenza vaccines.

RESUMO

This study evaluated the cellular heterogeneity and molecular mechanisms of hepatocellular carcinoma (HCC). Single cell RNA sequencing (scRNA-seq), transcriptomic data, histone lactylation-related genes were collected from public databases. Cell-cell interaction, trajectory, pathway, and spatial transcriptome analyses were executed. Differential expression and survival analyses were conducted. Western blot, Real-time reverse transcription PCR (qRT-PCR), and Cell Counting Kit 8 (CCK8) assay were used to detect the expression of αSMA, AKR1B10 and its target genes, and verify the roles of AKR1B10 in HCC cells. Hepatic stellate cell (HSC) subgroups strongly interacted with tumor cell subgroups, and their spatial distribution was heterogeneous. Two candidate prognostic genes (AKR1B10 and RMRP) were obtained. LONP1, NPIPB3, and ZSWIM6 were determined as AKR1B10 targets. Besides, the expression levels of AKR1B10 and αSMA were significantly increased in LX-2 + HepG2 and LX-2 + HuH7 groups compared to those in LX-2 group, respectively. sh-AKR1B10 significantly inhibited the HCC cell proliferation and change the expression of AKR1B10 target genes, Bcl-2, Bax, Pan Kla, and H3K18la at protein levels. Our findings unveil the pivotal role of HSCs in HCC pathogenesis through regulating histone lactylation.

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Background and purpose: Spontaneous aneurysmal subarachnoid hemorrhage (aSAH) is a common acute cerebrovascular disease characterized by severe illness, high mortality, and potential cognitive and motor impairments. We carried out a retrospective study at Fujian Provincial Hospital to establish and validate a model for forecasting functional outcomes at 6 months in aSAH patients who underwent interventional embolization. Methods: 386 aSAH patients who underwent interventional embolization between May 2012 and April 2022 were included in the study. We established a logistic regression model based on independent risk factors associated with 6-month adverse outcomes (modified Rankin Scale Score ≥ 3, mRS). We evaluated the model's performance based on its discrimination, calibration, clinical applicability, and generalization ability. Finally, the study-derived prediction model was also compared with other aSAH prognostic scales and the model's itself constituent variables to assess their respective predictive efficacy. Results: The predictors considered in our study were age, the World Federation of Neurosurgical Societies (WFNS) grade of IV-V, mFisher score of 3-4, secondary cerebral infarction, and first leukocyte counts on admission. Our model demonstrated excellent discrimination in both the modeling and validation cohorts, with an area under the curve of 0.914 (p < 0.001, 95%CI = 0.873-0.956) and 0.947 (p < 0.001, 95%CI = 0.907-0.987), respectively. Additionally, the model also exhibited good calibration (Hosmer-Lemeshow goodness-of-fit test: X2 = 9.176, p = 0.328). The clinical decision curve analysis and clinical impact curve showed favorable clinical applicability. In comparison to other prediction models and variables, our model displayed superior predictive performance. Conclusion: The new prediction nomogram has the capability to forecast the unfavorable outcomes at 6 months after intervention in patients with aSAH.

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KEY MESSAGE: Assembly of PUFA-attached TAGs is intimately correlated to turnover of newly formed membrane lipids in starch-deficient Chlamydomonas exposed to high light and nitrogen stress under air-aerated mixotrophic conditions. Triacylglycerols (TAGs) rich in polyunsaturated fatty acids (PUFAs) in microalgae have attracted extensive attention due to its promising application in nutraceuticals and other high-value compounds. Previous studies revealed that PUFAs accumulated in TAG primarily derived from the dominant membrane lipids, monogalactosyldiacylglycerolipid, digalactosyldiacylglycerol and diacylglycerol-N,N,N-trimethylhomoserine (DGTS), in the model alga Chlamydomonas reinhardtii. However, their respective contribution to PUFA-attached TAG integration has not been clearly deciphered, particularly in starchless Chlamydomonas that hyper-accumulates TAG. In this study, the starchless C. reinhardtii BAFJ5 was mixotrophically cultivated in photobioreactors aerated with air (0.04% CO2), and we monitored the dynamic changes in growth, cellular carbon and nitrogen content, photosynthetic activity, biochemical compositions, and glycerolipid remodeling under high light and nitrogen starvation conditions. The results indicated that multiple PUFAs continually accumulated in total lipids and TAG, and the primary distributors of these PUFAs gradually shifted from membrane lipids to TAG in stress-induced BAFJ5. The stoichiometry analyses showed that the PUFA-attached TAG assembly attributed to turnover of not only the major glycerolipids, but also the phospholipids, phosphatidylethanolamine (PE) and phosphatidylglycerol. Specifically, the augmented C16:3n3 and C18:3n3 in TAG mainly originated from de novo-synthesized galactolipids, while the cumulative C18:3n6 and C18:4n3 in TAG were intimately correlated with conversion of the newly formed DGTS and PE. These findings emphasized significance of PUFA-attached TAG formation dependent on turnover of de novo assembled membrane lipids in starch-deficient Chlamydomonas, beneficial for enhanced production of value-added lipids in microalgae.

Assuntos

Chlamydomonas reinhardtii , Ácidos Graxos Insaturados , Lipídeos de Membrana , Triglicerídeos , Triglicerídeos/metabolismo , Lipídeos de Membrana/metabolismo , Chlamydomonas reinhardtii/metabolismo , Ácidos Graxos Insaturados/metabolismo , Estresse Fisiológico , Amido/metabolismo , Nitrogênio/metabolismo , Galactolipídeos/metabolismo , Fotossíntese

RESUMO

Cardenolides are a class of steroidal glycoside compounds that are mainly distributed in plants, have significant physiological activity in the heart, and have been used clinically for over 200 years. To provide a reference for further research and development of these compounds, the phytochemical and biological properties of natural cardenolides (295 compounds in total) isolated between 2010 and 2023 from 17 families and hundreds of species belonging to 70-80 genera were reviewed. In vitro and in vivo studies have indicated that antitumor, antibacterial, and antiviral activities are the most commonly reported pharmacological properties of cardenolides. Antitumor activities have been thoroughly studied to understand their structure-activity relationships, revealing numerous potential anticancer molecules that lay the theoretical foundation for further development of traditional Chinese medicinal herbs and the creation of new drugs.

RESUMO

BACKGROUND: The lifestyle of most people was forced to change due to the COVID-19 pandemic. Perhaps after the pandemic, we will find that these subtle changes in life and from the depths of our hearts are thorough and profound. They may form our conceptual consensus and behavioral habits, becoming part of our long-term personal consciousness. This study explored the impacts of the COVID-19 pandemic on the future life behavior intentions of medical and health-related students studying at universities in China. METHODS: Electronic questionnaires were distributed to students studying at 3 universities in China. A total of 251 valid questionnaires were obtained, and the chi-squared test was used to compare the corresponding groups. RESULTS: In the future, students plan to pay more attention to wearing masks and maintaining social distance in public places, do more online shopping, have more meals at home or in the canteen, engage in less international travel, and have fewer gatherings with friends. However, compared with Chinese students, more non-Chinese students plan to increase domestic and international travel and reduce online learning. Furthermore, only among non-Chinese students did gender, urban or rural origin, and family economic conditions influence how the COVID-19 pandemic affected their future life behaviors. CONCLUSION: The COVID-19 pandemic changed the future life behavior intentions of medical and health-related students. The future behaviors of these students will impact the entire society. This study will help the government and policymakers predict and prepare for general lifestyle changes in our society.

RESUMO

Background: This study aimed to investigate whether dexmedetomidine provides survival benefit in critically ill patients with sepsis-induced coagulopathy (SIC). Methods: Patients with sepsis-induced coagulopathy admitted to the ICU were identified from the Medical Information Marketplace for Intensive Care (MIMIC)-IV database. They were divided into two groups: patients who started dexmedetomidine within 48 h of ICU admission and lasted for more than 4 h and patients who did not receive dexmedetomidine as a control group. The primary outcome was 28-day hospital mortality, the secondary outcome was in-hospital mortality, and the extended outcomes included duration of mechanical ventilation and vasopressor use, ICU stay, and hospital stay. Propensity score matching (PSM) analysis was used to match patients who received dexmedetomidine with those who did not, and multivariable Cox models and logistics models were used to account for baseline differences and unmeasured confounders. An external validation was performed with the Critical care database comprising patients with infection at Zigong Fourth People's Hospital. Results: After PSM, 592 patients who received dexmedetomidine were matched with 592 patients who did not receive dexmedetomidine. In the primary and secondary endpoints, dexmedetomidine was associated with a lower risk of 28-day hospital mortality (19.3% vs. 14.2%, hazard ratio (HR) 0.71; P = 0.020) and in-hospital mortality (22.3% vs. 16.4%, odds ratio (OR) 0.68; P = 0.017) in patients with SIC. Regarding the extended outcome, dexmedetomidine was also associated with a longer length of hospital stay (median 12.54 days vs. 14.87 days, P = 0.002) and longer ICU stay (median 5.10 days vs. 6.22 days, P = 0.009). In addition, the duration of mechanical ventilation was significantly increased in the dexmedetomidine group (median 41.62 h vs. 48.00 h, p = 0.022), while the duration of vasopressor use was not significantly different (median 36.67 h vs. 39.25 h, p = 0.194). Within 48 h of ICU stay, receiving a dose of dexmedetomidine greater than 0.474 µg/kg/h and continuous dexmedetomidine administration for 24-48 h may be associated with 28-day hospitalization outcomes in patients with SIC. External cohort validation also found that the use of dexmedetomidine after admission to the ICU can reduce 28-day mortality in patients with SIC. Conclusion: Dexmedetomidine administration is associated with reduced 28-day hospital mortality and in-hospital mortality in critically ill patients with SIC, and these findings deserve further verification in randomized controlled trials.

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The PowerPlex® 35GY System (Promega, USA) is an advanced eight-dye multiplex STR kit, incorporating twenty-three autosomal STR loci, eleven Y chromosome STR loci, one sex determining marker Amelogenin, and two quality indicators. This multiplex system includes 20 CODIS loci and up to 15 mini-STR loci with sizing values less than 250 bases. In this study, validation for PowerPlex® 35GY System was conducted following the guidelines of SWGDAM, encompassing sensitivity, precision, accuracy, concordance, species specificity, stutter, mixture, stability, and degraded DNA. The results from experiments demonstrated that the PowerPlex® 35GY System could effectively amplify DNA samples, with complete allele detection achieved at 125 pg. Moreover, over 90% of alleles from minor contributors were detected at a mixed ratio of 1:4. Additionally, the system was found to yield full profiles even in the presence of hematin, humic acid, and indigo. The PowerPlex® 35GY System demonstrated superior performance in the sensitivity and degraded DNA studies compared to a six-dye STR kit. Hence, it is evident that the PowerPlex® 35GY System is well-suited for forensic practice, whether in casework or for database samples. These findings provide strong support for the efficacy and reliability of the PowerPlex® 35GY System in forensic applications.

RESUMO

With the advancement of computer vision and sensor technologies, many multi-camera systems are being developed for the control, planning, and other functionalities of unmanned systems or robots. The calibration of multi-camera systems determines the accuracy of their operation. However, calibration of multi-camera systems without overlapping parts is inaccurate. Furthermore, the potential of feature matching points and their spatial extent in calculating the extrinsic parameters of multi-camera systems has not yet been fully realized. To this end, we propose a multi-camera calibration algorithm to solve the problem of the high-precision calibration of multi-camera systems without overlapping parts. The calibration of multi-camera systems is simplified to the problem of solving the transformation relationship of extrinsic parameters using a map constructed by multiple cameras. Firstly, the calibration environment map is constructed by running the SLAM algorithm separately for each camera in the multi-camera system in closed-loop motion. Secondly, uniformly distributed matching points are selected among the similar feature points between the maps. Then, these matching points are used to solve the transformation relationship between the multi-camera external parameters. Finally, the reprojection error is minimized to optimize the extrinsic parameter transformation relationship. We conduct comprehensive experiments in multiple scenarios and provide results of the extrinsic parameters for multiple cameras. The results demonstrate that the proposed method accurately calibrates the extrinsic parameters for multiple cameras, even under conditions where the main camera and auxiliary cameras rotate 180°.

RESUMO

Background: Knowledge about the pathogenesis of depression and treatments for this disease are lacking. Epigenetics-related circRNAs are likely involved in the mechanism of depression and have great potential as treatment targets, but their mechanism of action is still unclear. Methods: Circular RNA UBE2K (circ-UBE2K) was screened from peripheral blood of patients with major depressive disorder (MDD) and brain of depression model mice through high-throughput sequencing. Microinjection of circ-UBE2K overexpression lentivirus and adeno-associated virus for interfering with microglial circ-UBE2K into the mouse hippocampus was used to observe the role of circ-UBE2K in MDD. Sucrose preference, forced swim, tail suspension and open filed tests were performed to evaluate the depressive-like behaviors of mice. Immunofluorescence and Western blotting analysis of the effects of circ-UBE2K on microglial activation and immune inflammation. Pull-down-mass spectrometry assay, RNA immunoprecipitation (RIP) test and fluorescence in situ hybridization (FISH) were used to identify downstream targets of circ-UBE2K/ HNRNPU (heterogeneous nuclear ribonucleoprotein U) axis. Results: In this study, through high-throughput sequencing and large-scale screening, we found that circ-UBE2K levels were significantly elevated both in the peripheral blood of patients with MDD and in the brains of depression model mice. Functionally, circ-UBE2K-overexpressing mice exhibited worsened depression-like symptoms, elevated brain inflammatory factor levels, and abnormal microglial activation. Knocking down circ-UBE2K mitigated these changes. Mechanistically, we found that circ-UBE2K binds to heterogeneous nuclear ribonucleoprotein U (HNRNPU) to form a complex that upregulates the expression of the parental gene ubiquitin conjugating enzyme E2 K (UBE2K), leading to abnormal microglial activation and neuroinflammation and promoting the occurrence and development of depression. Conclusions: The findings of the present study revealed that the expression of circUBE2K, which combines with HNRNPU to form the circUBE2K/HNRNPU complex, is increased in microglia after external stress, thus regulating the expression of the parental gene UBE2K and mediating the abnormal activation of microglia to induce neuroinflammation, promoting the development of MDD. These results indicate that circ-UBE2K plays a newly discovered role in the pathogenesis of depression.

Assuntos

Transtorno Depressivo Maior , Modelos Animais de Doenças , Microglia , RNA Circular , Enzimas de Conjugação de Ubiquitina , Animais , RNA Circular/genética , RNA Circular/metabolismo , Microglia/metabolismo , Humanos , Camundongos , Masculino , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismo , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/metabolismo , Feminino , Depressão/genética , Depressão/metabolismo , Hipocampo/metabolismo , Camundongos Endogâmicos C57BL , Adulto , Pessoa de Meia-Idade

RESUMO

We quantified the lag time of vegetation response to drought in the Pearl River basin (PRB) based on the standardized precipitation evapotranspiration index (SPEI) and normalized difference vegetation index (NDVI), and constructed a vegetation loss probability model under drought stress based on the Bayesian theory and two-dimensional joint distribution. We further quantitatively evaluated the spatial variations of loss probability of four vegetation types (evergreen broadleaf forest, mixed forest, grassland, and cropland) under different drought intensities. The results showed that the drought risk in eastern West River, the upper reaches of North River and East River, and southern Pearl River Delta was obviously higher than that in other regions during 1982-2020. The response time of vegetation to drought in high-altitude areas in the upper reaches of PRB (mostly<3 month) was generally shorter than that in low altitude areas (>8 month). Drought exacerbated the probability of vegetation loss, with higher vulnerability of mixed forest than the other three vegetation types. The loss probability of vegetation was lower in northwestern PRB than that in central PRB.

Assuntos

Secas , Ecossistema , Florestas , Rios , Árvores , China , Árvores/crescimento & desenvolvimento , Estresse Fisiológico , Pradaria , Modelos Teóricos , Teorema de Bayes , Poaceae/crescimento & desenvolvimento

RESUMO

IMPORTANCE: Menstruation serves as an indicator of women's reproductive well-being and plays a pivotal role in their fertility; nevertheless, there remains an ongoing debate regarding the epidemiological evidence linking menstrual characteristics as well as fertility. OBJECTIVE: To explore the correlation between menstrual characteristics and fertility in women of reproductive age. DATA SOURCES: A comprehensive literature search was conducted using PubMed, Embase, Web of Science, and Cochrane libraries to identify research articles published up until February 9, 2024. STUDY SELECTION AND SYNTHESIS: We included all studies in which the relationship between menstrual characteristics and pregnancy rates among women of reproductive age was investigated. We excluded studies involving the administration of oral contraceptives, the application of assisted reproductive technologies, and individuals with a documented history of infertility or partners with a known history of infertility. MAIN OUTCOME MEASURE(S): Clinical pregnancy and miscarriage. RESULT(S): This meta-analysis was composed of nine studies involving a total of 399,966 women, and the evidential quality derived from these studies was deemed to be high with a low risk of bias. Compared with a normal menstrual cycle length (25-32 days), the impact of a short (<25 days) or long (>32 days) menstrual cycle on a woman's pregnancy was relatively insignificant ([odds ratio {OR}, 0.81; 95% confidence interval {CI}, 0.65-1.01; I2, 68%]; [OR, 0.89; 95% CI, 0.75-1.06; I2, 60%], respectively); however, a change in cycle length may increase the risk of miscarriage ([relative risk, 1.87; 95% CI, 1.11-3.15; I2, 0]; [relative risk, 1.66; 95% CI, 1.07, 2.57; I2, 43%], respectively). In comparison to women experiencing menarche at a typical age (12-14 years), those with a late age at menarche (>14 years) exhibited a decreased likelihood of pregnancy (OR, 0.92; 95% CI, 0.91-0.93; I2, 0%); and compared with women experiencing a normal duration of menstrual bleeding (4-7 days), those with a short duration of menstrual bleeding (<4 days) exhibited reduced fertility potential (OR, 0.86; 95% CI, 0.84-0.88; I2, 29%). CONCLUSION(S): Short and long menstrual cycle lengths may elevate women's susceptibility to spontaneous abortion, whereas late age at menarche as well as short duration of menstrual bleeding appear to be linked to diminished fertility among women of reproductive age. CLINICAL TRIAL REGISTRATION: PROSPERO CRD42023487458 (9 December 2023).