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1.
Trauma Violence Abuse ; : 15248380241275971, 2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39245948

RESUMEN

Bias-based cyberaggression-hateful and bias-based content and interactions via information and communication technologies-is a frequent experience for young internet users that can result in detrimental consequences for both individuals and society. Ample research has focused on the factors related to involvement in bias-based cyberaggression. This study systematically reviews the research published in the past decade about the investigations into exposure, vicarious and direct victimization, and aggression among young people (up to age 30). We aimed to provide a complex summarization of the research findings about the risk and protective factors and the consequences of experiences with bias-based cyberaggression-specifically the diverse manifestations of bias-based cyberaggression targeted toward ethnicity, race, nationality, religion, sexual orientation, gender, weight, and disability. Three academic databases (EBSCO, Scopus, and WoS) were searched and 41 articles were included in the review. The results show a dominant research focus on bias-based cyberaggression victimization and on the bias-based cyberaggression that targets ethnicity, race, nationality, and religion, leaving a gap in the knowledge about the different types of targeted group categories and bias-based cyberaggression perpetration. The identified risk factors for bias-based cyberaggression involvement included being a minority, low psychological well-being, other victimization experiences, higher internet use, and risky internet use. An overlap was found for bias-based cyberaggression involvement with other offline and online victimization experiences. This review showed limited knowledge about protective factors, namely the social-level and contextual factors. The identified factors, as well as the gaps in the knowledge, are discussed in relation to research implications and practice and policy implications.

2.
Plant Cell ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235115

RESUMEN

Multiple plant hormones, including strigolactone (SL), play key roles in regulating flowering time. The Arabidopsis (Arabidopsis thaliana) DWARF14 (AtD14) receptor perceives SL and recruits F-box protein MORE AXILLARY GROWTH2 (MAX2) and the SUPPRESSOR OF MAX2-LIKE (SMXL) family proteins. These interactions lead to the degradation of the SMXL repressor proteins, thereby regulating shoot branching, leaf shape, and other developmental processes. However, the molecular mechanism by which SL regulates plant flowering remains elusive. Here, we demonstrate that intact strigolactone biosynthesis and signaling pathways are essential for normal flowering in Arabidopsis. Loss-of-function mutants in both SL biosynthesis (max3) and signaling (Atd14 and max2) pathways display earlier flowering, whereas the repressor triple mutant smxl6/7/8 (s678) exhibits the opposite phenotype. Retention of AtD14 in the cytoplasm leads to its inability to repress flowering. Moreover, we show that nuclear-localized AtD14 employs dual strategies to enhance the function of the AP2 transcription factor TARGET OF EAT1 (TOE1). AtD14 directly binds to TOE1 in an SL-dependent manner and stabilizes it. In addition, AtD14-mediated degradation of SMXL7 releases TOE1 from the repressor protein, allowing it to bind to and inhibit the FLOWERING LOCUS T (FT) promoter. This results in reduced FT transcription and delayed flowering. In summary, AtD14 perception of SL enables the transcription factor TOE1 to repress flowering, providing insights into hormonal control of plant flowering.

3.
Int J Med Sci ; 21(11): 2127-2138, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39239555

RESUMEN

Background: Identification of the unknown pathogenic factor driving atherosclerosis not only enhances the development of disease biomarkers but also facilitates the discovery of new therapeutic targets, thus contributing to the improved management of coronary artery disease (CAD). We aimed to identify causative protein biomarkers in CAD etiology based on proteomics and 2-sample Mendelian randomization (MR) design. Methods: Serum samples from 33 first-onset CAD patients and 31 non-CAD controls were collected and detected using protein array. Differentially expressed analyses were used to identify candidate proteins for causal inference. We used 2-sample MR to detect the causal associations between the candidate proteins and CAD. Network MR was performed to explore whether metabolic risk factors for CAD mediated the risk of identified protein. Vascular expression of candidate protein in situ was also detected. Results: Among the differentially expressed proteins identified utilizing proteomics, we found that circulating Golgi protein 73 (GP73) was causally associated with incident CAD and other atherosclerotic events sharing similar etiology. Network MR approach showed low-density lipoprotein cholesterol and glycated hemoglobin serve as mediators in the causal pathway, transmitting 42.1% and 8.7% effects from GP73 to CAD, respectively. Apart from the circulating form of GP73, both mouse model and human specimens imply that vascular GP73 expression was also upregulated in atherosclerotic lesions and concomitant with markers of macrophage and phenotypic switching of vascular smooth muscle cells (VSMCs). Conclusions: Our study supported GP73 as a biomarker and causative for CAD. GP73 may involve in CAD pathogenesis mainly via dyslipidemia and hyperglycemia, which may enrich the etiological information and suggest future research direction on CAD.


Asunto(s)
Biomarcadores , Enfermedad de la Arteria Coronaria , Proteínas de la Membrana , Análisis de la Aleatorización Mendeliana , Proteómica , Humanos , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/patología , Ratones , Animales , Proteínas de la Membrana/genética , Proteínas de la Membrana/sangre , Masculino , Femenino , Biomarcadores/sangre , Persona de Mediana Edad , LDL-Colesterol/sangre , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Estudios de Casos y Controles , Aterosclerosis/sangre , Aterosclerosis/genética
4.
Front Microbiol ; 15: 1422272, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39224220

RESUMEN

To study the effect of melatonin supplementation on the gut microbes of broilers, 160 healthy 3-week-old Ross 308 broilers with similar body weights were selected and randomly divided into four groups (M0, M20, M40, and M80) supplemented with 0, 20, 40, or 80 mg/kg melatonin. The results showed that the abundance-based coverage estimator (ACE) index of cecum microorganisms was significantly lower in the M80 group. The dominant phyla of intestinal contents in the M0, M20, M40, and M80 groups were Bacteroidetes and Firmicutes. The M40 group showed an increase in the relative abundance of Bacteroidetes spp. in the intestine, while the relative abundance of Ruminococcus spp. in the intestine of the M20, M40, and M80 groups was significantly greater than that of the M0 group. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses revealed that the supplementation of melatonin increases the expression of genes related to cellular processes (cell motility, cell growth and death, and cellular community-eukaryotes), environmental information processing (membrane transport and signal transduction), and genetic information processing (transport and transcription), and Cluster of Orthologous Groups (COG) of proteins functional analyses revealed that the supplementation of melatonin resulted in a significant increase in cellular processes and signaling (cell motility, signal transduction mechanisms, intracellular trafficking, secretion, and vesicular transport), information storage and processing (RNA processing and modification, chromatin structure and dynamics, translation, ribosomal structure, and biogenesis), metabolism (energy production and conversion, lipid transportation and metabolism, inorganic ion transport and metabolism, secondary metabolite biosynthesis, transport, and catabolism), and poorly characterized (general function prediction only). In summary, supplementation of feed with melatonin can increase the diversity of intestinal microorganisms and the relative abundance of Bacteroides and Firmicutes in the cecum, improve digestive ability and nutrient absorption ability, and positively regulate the metabolic ability of broilers.

5.
Heliyon ; 10(16): e36029, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39224331

RESUMEN

In recent years, live streaming commerce (LSC) has become a popular research topic. However, current studies on LSC are relatively insufficient, and analyses have generally focused on its specific aspects, lacking a comprehensive and systematic perspective. Hence, this study utilises CiteSpace to undertake a visual bibliometric analysis aimed at delineating the knowledge framework and evolution of LSC and indicates future research directions to provide a comprehensive picture of the development of this dynamic field over the past six years. The results show that LSC is a thriving subject with several growing annual publications. Additionally, a strong collaboration exists between institutions and authors. Further, 'influence', 'consumer behaviour' and 'consumer purchase intention' are more popular in this domain and have assumed a leading position in recent research. Moreover, novel research trajectories have emerged, indicating interdisciplinary integration within the field. This study is innovative as it combines live streaming with commerce, analyses six years of literature, and builds an accurate and comprehensive knowledge framework within this domain. By identifying current gaps, this study contributes to the literature by addressing prior study limitations, enriching the knowledge base, providing crucial research directions for future exploration, and inspiring scholars to efficiently find research topics.

6.
Asian J Psychiatr ; 101: 104211, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39226756

RESUMEN

The affective pathway to psychosis implicates affective symptoms and neuroticism as mediating steps between childhood trauma and symptoms of schizophrenia. Prior research seldom examined the interplay between childhood trauma, resilience, personality, social functioning and symptoms in schizophrenia patients. This study recruited 290 schizophrenia patients, and constructed a regularized partial correlation network of childhood trauma, resilience, big-five personality traits, symptoms and social functioning. We further applied flow diagram and shortest path analysis to clarify how different childhood trauma types would contribute to and reach different symptoms. In the network, emotional and physical abuse showed the highest expected influence, and resilience showed the highest strength. In flow diagrams, all nodes together contributed two-thirds of variance of social functioning (which had highest predictability). Among childhood trauma types, emotional abuse contributed most to positive symptoms; physical neglect contributed most to negative, depressive and disorganized symptoms. Childhood abuse reached positive symptoms via neuroticism and depressive symptoms, yet it reached negative symptoms via physical neglect and social functioning. Childhood neglect reached positive symptoms via resilience, conscientiousness, neuroticism and depressive symptoms, yet it reached negative symptoms via social functioning. Our findings support that different childhood trauma types contribute to different symptoms, and interacts with resilience, personality and social functioning.

7.
J Natl Cancer Cent ; 4(2): 135-141, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39282588

RESUMEN

Background: The paclitaxel liposome formulation, encapsulating paclitaxel within a phospholipid bilayer, addresses the insolubility of traditional paclitaxel formulations, thereby reducing toxicity without compromising its antitumor efficacy. Methods: This multicenter, open-label, non-inferiority randomized controlled trial (ChiCTR2000038555) evaluates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin (PLC vs. PC) as first-line therapy in patients with epithelial ovarian cancer. Results: An analysis of median progression-free survival (PFS) revealed non-inferior outcomes between 263 patients in the PLC group and 260 patients in the PC group (32.3 vs. 29.9 months, hazard ratio [HR], 0.89 [95% CI, 0.64-1.25]), using a non-inferior margin of 1.3. Although the overall incidence of treatment-related adverse events was comparable between groups, the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen. Conclusion: The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of paclitaxel and carboplatin regarding therapeutic efficacy, with an enhanced safety profile marked by reduced non-hematologic toxicities.

8.
Elife ; 132024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39283314

RESUMEN

Experimental detection of residues critical for protein-protein interactions (PPI) is a time-consuming, costly, and labor-intensive process. Hence, high-throughput PPI-hot spot prediction methods have been developed, but they have been validated using relatively small datasets, which may compromise their predictive reliability. Here, we introduce PPI-hotspotID, a novel method for identifying PPI-hot spots using the free protein structure, and validated it on the largest collection of experimentally confirmed PPI-hot spots to date. We explored the possibility of detecting PPI-hot spots using (i) FTMap in the PPI mode, which identifies hot spots on protein-protein interfaces from the free protein structure, and (ii) the interface residues predicted by AlphaFold-Multimer. PPI-hotspotID yielded better performance than FTMap and SPOTONE, a webserver for predicting PPI-hot spots given the protein sequence. When combined with the AlphaFold-Multimer-predicted interface residues, PPI-hotspotID yielded better performance than either method alone. Furthermore, we experimentally verified several PPI-hotspotID-predicted PPI-hot spots of eukaryotic elongation factor 2. Notably, PPI-hotspotID can reveal PPI-hot spots not obvious from complex structures, including those in indirect contact with binding partners. PPI-hotspotID serves as a valuable tool for understanding PPI mechanisms and aiding drug design. It is available as a web server (https://ppihotspotid.limlab.dnsalias.org/) and open-source code (https://github.com/wrigjz/ppihotspotid/).


Asunto(s)
Mapeo de Interacción de Proteínas , Mapeo de Interacción de Proteínas/métodos , Conformación Proteica , Biología Computacional/métodos , Proteínas/química , Proteínas/metabolismo , Unión Proteica , Programas Informáticos
9.
Nat Commun ; 15(1): 8120, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39285179

RESUMEN

Defect tolerance is a critical enabling factor for efficient lead-halide perovskite materials, but the current understanding is primarily on band-edge (cold) carriers, with significant debate over whether hot carriers can also exhibit defect tolerance. Here, this important gap in the field is addressed by investigating how intentionally-introduced traps affect hot carrier relaxation in CsPbX3 nanocrystals (X = Br, I, or mixture). Using femtosecond interband and intraband spectroscopy, along with energy-dependent photoluminescence measurements and kinetic modelling, it is found that hot carriers are not universally defect tolerant in CsPbX3, but are strongly correlated to the defect tolerance of cold carriers, requiring shallow traps to be present (as in CsPbI3). It is found that hot carriers are directly captured by traps, instead of going through an intermediate cold carrier, and deeper traps cause faster hot carrier cooling, reducing the effects of the hot phonon bottleneck and Auger reheating. This work provides important insights into how defects influence hot carriers, which will be important for designing materials for hot carrier solar cells, multiexciton generation, and optical gain media.

10.
Am J Transl Res ; 16(8): 3582-3598, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39262707

RESUMEN

OBJECTIVE: The aim of the present study was to assess the therapeutic impact of diosgenin derivative ML5 on Parkinson's disease (PD) and explore the mechanism underlying mitochondrial biogenesis and fusion/fission. METHODS: We established 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse models and N-methyl-4-phenylpyridinium iodide (MPP+)-induced cell models of PD. The pole test and forced swimming test were used to detect the motor coordination and depressive symptoms in mice. The influence of ML5 on dopaminergic neuronal injury was investigated. Meanwhile, adenosine triphosphate (ATP) content, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) production were measured to evaluate mitochondrial function. Confocal and transmission electron microscopy were used to detect mitochondrial morphology of cell. The expression of mitochondrial biogenesis-related proteins was measured by Western blotting. RESULTS: The administration of ML5 showed the neuroprotection against MPTP-induced damage in vivo and in vitro. The levels of ATP, MMP, and ROS were restored after ML5 administration. In addition, we observed that ML5 preserved the mitochondrial network morphology and inhibited mitochondrial fission. Furthermore, the amelioration of mitochondrial dysfunction was mediated by enhancing 5'-monophosphate-activated protein kinase (AMPK) and peroxisome proliferators-activated receptor γ coactivator-l alpha (PGC-1α) expression, which activated its downstream modulators leading to the enhancing of mitochondrial biogenesis and the balance of mitochondrial fusion/fission. CONCLUSION: ML5 can protect the PD models against MPTP/MPP+-induced mitochondrial dysfunction and neuronal injury via promoting AMPK/PGC-1α signaling activation and be used as a therapeutic drug for PD treatment.

11.
Front Immunol ; 15: 1404542, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39267743

RESUMEN

Background: COVID-19 began in December 2019, rapidly spreading worldwide. China implemented a dynamic zero-COVID strategy and strict control measures after the outbreak. However, Guangzhou city ended closed-off management by the end of November 2022, leading to exposure to SARS-CoV-2. Despite most hospitalized patients being infected or co-infected with SARS-CoV-2, some remained uninfected. We report two cases of bacterial pneumonia with elevated globulin levels not infected with SARS-CoV-2, aiming to identify protection factors of SARS-CoV-2 infection and provide a scientific basis for SARS-CoV-2 prevention. Case presentation: Case 1, a 92-year-old male, admitted on October 21, 2022, developed worsening cough and sputum after aspiration, diagnosed with bacterial pneumonia with Pseudomonas aeruginosa, Escherichia coli (CRE) and carbapenem-resistant Acinetobacter baumannii (CRAB) infections. He was treated with imipenem anti-infective therapy and mechanical ventilation, then switched to a combination of meropenem, voriconazole and amikacin anti-infective therapy due to recurrent infections and septic shock, and died of sepsis on 8 January 2023. Case 2 is an 82-year-old male admitted on 30 September 2022, with recurrent cough, sputum, and shortness of breath, diagnosed with bacterial pneumonia with carbapenem-resistant Klebsiella pneumoniae (CRKP) and Mycobacterium pneumoniae infections. He was treated with ventilator-assisted ventilation, meropenem, amikacin, tigecycline and mucomycin nebulization and discharged with improvement on 26 October. He was readmitted on 21 November 2022 and diagnosed with bacterial pneumonia. He was treated with cefoperazone sulbactam, amikacin, meropenem and fluconazole and discharged on 31 December. Neither patient was infected with SARS-CoV-2 during hospitalization. Notably, their globulin levels were elevated before SARS-CoV-2 exposure, gradually decreasing afterward. Conclusions: Patients with bacterial pneumonia with high globulin levels likely have large amounts of immunoglobulin, and that immunoglobulin cross-reactivity causes this protein to be involved in clearing SARS-CoV-2 and preventing infection. Therefore, bacterial pneumonia patients with high globulin levels included in this study were not infected with SARS-CoV-2. After exposure to SARS-CoV-2, the amount of globulin in the patient's body was reduced because it was used to clear SARS-CoV-2. The results of this study are expected to provide a theoretical basis for the study of the mechanism of prevention and treatment of SARS-CoV-2 infection.


Asunto(s)
COVID-19 , Neumonía Bacteriana , SARS-CoV-2 , Humanos , Masculino , COVID-19/complicaciones , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/diagnóstico , Anciano de 80 o más Años , Antibacterianos/uso terapéutico
12.
Oncol Lett ; 28(5): 523, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39268170

RESUMEN

Endometriosis-associated adenocarcinoma of the rectum is rare and is usually misdiagnosed as colorectal carcinoma or other gynecological tumors. In the current report, the clinicopathological features of endometriosis-associated adenocarcinoma of the rectum in 2 patients were retrospectively analyzed and a literature review regarding this rare malignancy is presented. Case 1, a 49-year-old postmenopausal female patient, was admitted to Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology (Wuhan, China) due to a pelvic mass. Pelvic MRI revealed a 4.5×3.7-cm mass in the rectal wall, which severely adhered to the uterine wall. Microscopically, moderately differentiated glandular adenocarcinoma diffusely extended throughout all intestinal wall layers. Adenomyosis was found in the uterine body adherent to the rectum. Case 2, a 38-year-old reproductive female patient, presented with hematochezia. Histopathology of the resected tumor demonstrated benign endometriosis foci and atypical hyperplasia glands contiguous with endometrioid carcinoma invading the intestinal wall, and no other primary tumor sites were found, which satisfied the criteria for the diagnosis of malignant transformation of endometriosis of the rectum. Immunohistochemical (IHC) staining of both tumors revealed a Müllerian origin but not an intestinal origin. Furthermore, next-generation sequencing detected mutations of the BRCA1 (c.329dup), KRAS (c.35G>T), PIK3CA (c.3140A>G) and PTEN (c.750_751del) genes, and that microsatellite instability was high in case 1. In conclusion, endometriosis-associated adenocarcinoma of the rectum is a rare malignant tumor that should be distinguished from colorectal carcinoma for optimal treatment. Surgery and pathologic examination with IHC staining, even with molecular analysis, are essential for the final diagnosis. Primary cytoreductive surgery with resection of all macroscopic detectable lesions should be performed whenever possible. More prospective, multicenter, large-scale trials are required to examine the regimens and therapeutic value of adjuvant chemotherapy or radiology.

13.
Heliyon ; 10(17): e36685, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39286176

RESUMEN

Hypertensive disorders of pregnancy (HDP) are multifaceted syndromes unique to pregnancy, characterized by increased blood pressure, edema, and proteinuria. Patients with HDP exhibit signs of endothelial dysfunction, possibly linked to increased myeloperoxidase (MPO) level and aberrant oxidative stress. Additionally, altered level of tissue inhibitor of metalloproteinase-1 (TIMP1) protein is associated with placental ischemia, hypoxia, and maternal vascular endothelial damage. Preeclampsia (PE) represents a critical stage of HDP that poses severe threats to maternal and fetal safety. This study aimed to determine the relationship between MPO and TIMP1 polymorphisms and the risk of PE in the Chinese Han population. Single nucleotide polymorphisms (SNPs), including MPO rs7208693, MPO rs2243828, and TIMP1 rs6609533, were genotyped in 170 patients with PE and 303 control participants. No significant association was observed between MPO polymorphisms (rs7208693 and rs2243828) and the risk of PE, whereas significant association between the TIMP1 rs6609533 A > G SNP and PE susceptibility was found. Specifically, individuals with the GG or AG genotypes had elevated risk of PE compared to those harboring the AA genotype. Furthermore, in the PE group, patients carrying the G allele were more likely to experience fetal growth restriction (FGR). In the non-PE group, the association between the G allele and the risk of FGR was not evident. In conclusion, the TIMP1 rs6609533 G allele in Chinese Han women was identified as a risk factor for PE. Our results indicated that the TIMP1 rs6609533 SNP can serve as a biomarker for the clinical diagnosis and treatment of PE.

14.
Sensors (Basel) ; 24(17)2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39275764

RESUMEN

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.

15.
J Hazard Mater ; 480: 135827, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39276736

RESUMEN

The Ni hyperaccumulator Odontarrhena chalcidica (formerly Alyssum murale), exhibits a significant capacity to accumulate Zn in the roots. However, the molecular mechanisms underlying the variation in Ni and Zn accumulation are poorly understood. Here, we isolated a homolog of heavy metal ATPase 3 from O. chalcidica (OcHMA3) and characterized its functions using heterologous systems. Phylogenetic analysis revealed that OcHMA3 protein shares 87.6 % identity with AtHMA3, with similar metal binding sites to other HMA3 proteins. Heterologous expression of OcHMA3 in yeast increased sensitivity to Cd, Ni and Zn, suggesting it functions as a broad-specificity transporter. Further investigation showed OcHMA3 is constitutively expressed in the roots and localized to the tonoplast. Overexpression of OcHMA3 in A. thaliana shoots increased its roots Zn concentrations by 41.9 % - 74.1 %. However, overexpression of OcHMA3 in roots enhanced its tolerance to Cd and increased roots Cd concentrations by 50.9 % - 90.6 %. Our findings indicated OcHMA3 is responsible for Zn sequestration in root vacuoles, likely leading to Zn retention in roots and subsequent Ni hyperaccumulation in shoots. This study elucidates the molecular mechanism of Ni and Zn accumulation in O. chalcidica, and identifies OcHMA3 as a potential gene for developing Zn-rich plants and for phytoextraction in Cd-contaminated soils.

16.
Lancet Oncol ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39276785

RESUMEN

BACKGROUND: Ovarian clear cell carcinoma rarely responds to second-line chemotherapy, the recommended treatment for relapsed epithelial ovarian cancer. Here, we report the activity and safety of sintilimab in combination with bevacizumab in patients with relapsed or persistent ovarian clear cell carcinoma. METHODS: In the prospective, multicentre, single-arm, phase 2 INOVA trial, patients aged 18-75 years with histologically confirmed relapsed or persistent ovarian clear cell carcinoma were enrolled from eight tertiary hospitals in China. Eligible patients had an Eastern Cooperative Oncology Group performance status score of 0-2 and previous exposure to at least one cycle of platinum-containing chemotherapy. Enrolled patients received sintilimab (200 mg) and bevacizumab (15 mg/kg) intravenously every 3 weeks until disease progression. The primary endpoint was objective response rate assessed by independent central review based on Response Evaluation Criteria in Solid Tumours version 1.1. Eligible enrolled patients who received at least one cycle of treatment and had at least one tumour response assessment following the baseline assessment per protocol were included in the activity analysis. Patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04735861) and is ongoing. FINDINGS: Between April 8, 2021, and July 3, 2023, 51 patients were screened and 41 patients received at least one dose of sintilimab in combination with bevacizumab. Response evaluation was completed in 37 patients. Objective responses were observed in 15 patients (objective response rate 40·5%; 95% CI 24·8-57·9), of which five (14%) were complete responses and ten (27%) were partial responses. At data cutoff (Jan 29, 2024), the median follow-up was 16·9 months (IQR 7·5-23·4). Three (7%) patients developed grade 3 treatment-related adverse events including one patient with proteinuria, one patient with myocarditis, and one patient with rash. No treatment-related adverse events of worse than grade 3 severity were recorded. Treatment-related serious adverse events occurred in two (5%) patients including one patient with immune-related myocarditis and another with hypertension and renal dysfunction. No treatment-related deaths occurred. INTERPRETATION: Sintilimab in combination with bevacizumab showed promising anti-tumour activity and manageable safety in patients with relapsed or persistent ovarian clear cell carcinoma. Larger, randomised trials are warranted to compare this low-toxicity, chemotherapy-free combinatorial regimen with standard chemotherapy. FUNDING: National Key Technology Research and Development Program of China, National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Innovent Biologics. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

17.
Ann Hepatol ; : 101571, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39276987

RESUMEN

INTRODUCTION AND OBJECTIVES: This research aims to evaluate the efficacy and safety of prophylactic antibiotics in patients with alcohol-related liver disease (ALD). MATERIALS AND METHODS: We systematically searched databases including PubMed, Embase, Cochrane, and Web of Science up to October 2023. Our scope encompassed the influence of prophylactic antibiotics on all-cause mortality, infection, variceal bleeding, hepatic encephalopathy (HE), hepatorenal syndrome (HRS), adverse events (AE), fungal infection, clostridioides difficile infection (CDI), and multidrug-resistant (MDR) bacterial infection. Additionally, total bilirubin, creatinine, platelet counts, and plasma endotoxin levels were also analyzed. RESULTS: After comprehensive selection, 10 studies with 974 participants were included for further analysis. The study demonstrated that prophylactic antibiotic therapy was associated with reductions in infection rates, HE incidence, variceal bleeding, and all-cause mortality. The treatment did not increase the incidence of AE, fungal infection, and CDI, but it did raise the MDR bacteria infection rate. The analysis revealed no significant protective effect of antibiotic prophylaxis on total bilirubin and creatinine levels. Furthermore, the administration of antibiotics led to marginal increases in platelet counts, a minor reduction in endotoxin concentrations, and a subtle enhancement in HRS; however, these changes did not reach statistical significance. CONCLUSIONS: Prophylactic antibiotic therapy was an effective and safe treatment for advanced ALD. To mitigate the risk of MDR bacterial infections, a strategy of selective intestinal decontamination could be advisable. Future investigations should prioritize varied ALD patient populations with extended follow-up periods and assorted antibiotic regimens to solidify the efficacy and safety of ALD treatments.

18.
Gene ; : 148949, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39278374

RESUMEN

C-terminal kinesin motor KIFC1 is increasingly concerned with an essential role in germ cell development. During the spermatogenesis of mice, rats, and crustaceans, KIFC1 functions in regulating meiotic chromosome separation, acrosome vesicle transportation, and nuclear morphology maintenance. The expression pattern of KIFC1 is conservatively concentrated at the acrosome and nucleus of haploid sperm cells. However, whether KIFC1 has similar functions in non-human primates remains unknown. In this study, we constructed the testis-specific cDNA library and cloned different transcripts of KIFC1 based on the genomic sequence. New variants of KIFC1 were identified, and showed different functional domains from the predicted isoforms. The spatio-temporal expression of KIFC1 proteins in seminiferous tubules of rhesus monkeys showed an obvious nuclear localization, specifically expressed in the spermatocytes and early haploid spermatids. The transcripts of KIFC1 also exhibited considerable expression in the nucleus of rhesus LLC-MK2 cells. Besides, we demonstrated that KIFC1 located at the acrosome and microtubule flagella of the mature sperm, and KIFC1 inhibition resulted in sperm tail deformation as well as increased the instability of head-to-tail connection. In summary, this study filled a gap in the reproductive research of the KIFC1 gene in non-human primates.

19.
BMC Oral Health ; 24(1): 1080, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39272161

RESUMEN

BACKGROUND: The microvascular free fibula (MFF) flap is a reliable treatment modality for mandibular reconstruction and is suitable for dental implant placement after oncologic surgery. The most common issue with the MFF flap is its limited bone height, which typically results in excessive interarch space and complicates prosthodontic therapy. Overcoming the physical limitations from tumor excision and reducing the treatment time for prosthodontic rehabilitation to improve quality of life are critical clinical challenges. CASE PRESENTATION: A 64-year-old male with lower left gum and bilateral buccal cancer received a single-layer microvascular MFF flap to reconstruct a mandibular defect post-tumor excision. He underwent a bilateral modiolus Z-plasty combined with a skin flap debulking procedure to relieve oral contracture, achieving adequate mouth opening for prosthodontic rehabilitation. Scar tissue bands on the bilateral cheeks significantly affected retention and stability, hampering dental impression performance. The patient sought prosthodontic rehabilitation to enhance his chewing function and quality of life promptly. Prosthodontic rehabilitation with all-on-4 implant therapy, utilizing computer-aided design and computer-assisted manufacturing (CAD/CAM), was completed within one month. CONCLUSION: This case utilized the all-on-4 implant system to address the insufficient fibular height for conventional dental implant placements. Dental CAD/CAM was employed to mill custom prosthetic abutments and a large titanium framework for the implant bar overdenture, compensating for the excessive interarch space between the grafted fibula and maxilla. This treatment approach successfully shortened the prosthodontic rehabilitation time and overcame anatomical limitations.


Asunto(s)
Diseño Asistido por Computadora , Prótesis Dental de Soporte Implantado , Humanos , Masculino , Persona de Mediana Edad , Reconstrucción Mandibular/métodos , Peroné/trasplante , Neoplasias de la Boca/cirugía , Neoplasias de la Boca/rehabilitación , Implantes Dentales , Colgajos Tisulares Libres , Implantación Dental Endoósea/métodos
20.
Artículo en Inglés | MEDLINE | ID: mdl-39222903

RESUMEN

INTRODUCTION: This study investigates the causal relationship between plasma metabolites and stroke. METHOD: The primary analytical approach employed was the inverse variance weighted (IVW) method, complemented by the weighted median (WM) and MR Egger methods for Additionally, validation of the identified plasma metabolites was performed using the Steiger test and LD linkage disequilibrium score. Furthermore, the main results were confirmed through data from the UK Biobank. RESULT: The IVW analysis revealed the most notable negative association found in X-17335 levels (OR [95 % CI]: 0.82 [0.72, 0.94]). On the other hand, the strongest positive effect was seen in the 5'-homophase (AMP) to phase ratio (OR [95 % CI]: 1.17 [1.03, 1.32]). Moving on to the validation dataset, the most significant positive effect was observed in the 13 HODE+9-HODE levels (OR [95 % CI]: 0.996 [0.993, 0.999]), whereas the most significant negative effect was seen in the Dihydroxide levels (OR [95 % CI]: 1.004 [1.00, 1.007]). Notably, Alpha ketoglutarate levels exhibited strong causal effects in both datasets (OR 0.908 [0.841, 0.981], p = 0.0144). Enrichment analysis highlighted the association of Alpha ketoglutarate levels with five plasma metabolites in metabolic pathways relevant to stroke, specifically Arginine biosynthesis, Butanoate metabolism, Citrate cycle (TCA cycle), Alanine, aspartate, and glutamate metabolism, and Lipid acid metabolism, all linked to oxoglutaric acid. CONCLUSION: The discovery dataset showed the most significant positive effect of the 5'-homophase (AMP) to phase ratio, while the validation dataset revealed the most significant positive effect of the 13 HODE+9-HODE levels. Additionally, alpha ketoglutarate may offer a potential protective effect on stroke by influencing five metabolic pathways that intersect with Oxoglutaric acid during the progression of the condition.


Asunto(s)
Análisis de la Aleatorización Mendeliana , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/genética , Polimorfismo de Nucleótido Simple
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