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1.
Int J Surg ; 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38652147

ABSTRACT

BACKGROUND: We aimed to compare combined intraoperative chemotherapy and surgical resection with curative surgical resection alone in colorectal cancer patients. METHODS: We performed a multicenter, open-label, randomized, phase III trial. All eligible patients were randomized and assigned to intraoperative chemotherapy and curative surgical resection or curative surgical resection alone (1:1). Survival actualization after long-term follow-up was performed in patients analyzed on an intention-to-treat basis. RESULTS: From January 2011 to January 2016, 696 colorectal cancer patients were enrolled and randomly assigned to intraoperative chemotherapy and radical surgical resection (n=341) or curative surgical resection alone (n=344). Intraoperative chemotherapy with surgical resection showed no significant survival benefit over surgical resection alone in colorectal cancer patients (3-year DFS: 91.1% vs. 90.0%, P=0.328; 3-year OS: 94.4% vs. 95.9%, P=0.756). However, colon cancer patients benefitted from intraoperative chemotherapy, with a relative 4% reduction in liver and peritoneal metastasis (HR=0.336, 95% CI: 0.148-0.759, P=0.015) and a 6.5% improvement in 3-year DFS (HR=0.579, 95% CI: 0.353-0.949, P=0.032). Meanwhile, patients with colon cancer and abnormal pretreatment CEA levels achieved significant survival benefits from intraoperative chemotherapy (DFS: HR=0.464, 95% CI: 0.233-0.921, P=0.029 and OS: (HR=0.476, 95% CI: 0.223-1.017, P=0.049). CONCLUSIONS: Intraoperative chemotherapy showed no significant extra prognostic benefit in total colorectal cancer patients who underwent radical surgical resection; however, in colon cancer patients with abnormal pretreatment serum CEA levels (> 5 ng/ml), intraoperative chemotherapy could improve long-term survival.

3.
J Natl Compr Canc Netw ; 22(3)2024 03 18.
Article in English | MEDLINE | ID: mdl-38498975

ABSTRACT

BACKGROUND: Neoadjuvant anti-PD-1 therapy has shown encouraging efficacy in patients with deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer (LARC), which suggests its potential as a curative-intent therapy and a promising treatment option for organ preservation. We aimed to investigate the long-term outcomes of patients with dMMR/MSI-H LARC who experienced clinical complete response (cCR) after anti-PD-1 therapy. METHODS: We retrospectively analyzed patients with dMMR/MSI-H LARC who achieved cCR and received nonoperative management following neoadjuvant anti-PD-1-based treatment from 4 Chinese medical centers. Patients were followed up for at least 1 year after they achieved cCR, their clinical data were collected, and survival outcomes were analyzed using the Kaplan-Meier method. RESULTS: A total of 24 patients who achieved cCR and received nonoperative management from March 2018 to May 2022 were included, with a median age of 51.0 years (range, 19.0-77.0 years). The median treatment course to reach cCR was 6.0 (range, 1.0-12.0). Fifteen patients (62.5%) continued their treatments after experiencing cCR, and the median treatment course was 17.0 (range, 3.0-36.0). No local regrowth or distant metastasis was observed in a median follow-up time of 29.1 months (range, 12.6-48.5 months) after cCR. The 3-year disease-free and overall survivals were both 100%. CONCLUSIONS: Patients with dMMR/MSI-H locally advanced or low-lying rectal cancer who achieved cCR following anti-PD-1-based therapy had promising long-term outcomes. A prospective clinical trial with a larger sample size is required to further validate these findings.


Subject(s)
Colorectal Neoplasms , Rectal Neoplasms , Adult , Aged , Humans , Middle Aged , Young Adult , Colorectal Neoplasms/genetics , DNA Mismatch Repair , Immunotherapy , Microsatellite Instability , Neoadjuvant Therapy , Rectal Neoplasms/genetics , Rectal Neoplasms/therapy , Retrospective Studies , Treatment Outcome
4.
J Org Chem ; 89(5): 2939-2950, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38381084

ABSTRACT

Herein, we developed a highly selective, efficient, and simple method for direct transamidation of thioamides with amines, promoted by commercially available acetophenone under metal-/solvent-free conditions. The reaction tolerated a wide range of functional groups and substrates, including single- or double-thioamides, benzylamines, or alkyl/cycloalkyl-substituted aliphatic amines. The present protocol can be applied to gram-scale in good yields. In addition, the Pt-/Ni-complexes of double-transamidation products were obtained in good to excellent yields. The investigation of photophysical properties indicated that the fluorescence spectra of Pt-complexes showed an emission band centered at 550-750 nm and exhibited red fluorescence when irradiated by a UV lamp (365 nm).

5.
BMC Cancer ; 24(1): 164, 2024 Feb 02.
Article in English | MEDLINE | ID: mdl-38302968

ABSTRACT

BACKGROUND: For high-risk stageIImismatch repair deficient (dMMR) colon cancers, the benefit of adjuvant chemotherapy remains debatable. The principal aim of this study was to evaluate the prognostic value of high-risk factors and the effect of oxaliplatin-based adjuvant chemotherapy among dMMR stageIIcolon cancers. METHODS: Patients with stage II dMMR colon cancers diagnosed between June 2011 and May 2018 were enrolled in the study. Clinicopathological characteristics, treatment, and follow-up data were retrospectively collected. The high-risk group was defined as having one of the following factors: pT4 disease, fewer than twelve lymph nodes harvested (< 12 LNs), poorly differentiated histology, perineural invasion (PNI), lymphatic vascular invasion (LVI), or elevated preoperative carcinoembryonic antigen (CEA). The low-risk group did not have any risk factors above. Factors associated with disease-free survival (DFS) were included in univariate and multivariate Cox analyses. RESULTS: We collected a total of 262 consecutive patients with stage II dMMR colon cancer. 179 patients (68.3%) have at least one high-risk factor. With a median follow-up of 50.1 months, the low-risk group was associated with a tended to have a better 3-year DFS than the high-risk group (96.4% vs 89.4%; P = 0.056). Both elevated preoperative CEA (HR 2.93; 95% CI 1.26-6.82; P = 0.013) and pT4 disease (HR 2.58; 95% CI 1.06-6.25; P = 0.037) were independent risk factors of recurrence. Then, the 3-year DFS was 92.6% for the surgery alone group and 88.1% for the adjuvant chemotherapy group (HR 1.64; 95% CI 0.67-4.02; P = 0.280). Furthermore, no survival benefit from oxaliplatin-based adjuvant chemotherapy was observed in the high-risk group and in the subgroups with pT4 disease or < 12 LNs. CONCLUSIONS: These data suggests that not all high-risk factors have a similar impact on stage II dMMR colon cancers. Elevated preoperative CEA and pT4 tumor stage are associated with increased recurrence risk. However, oxaliplatin-based adjuvant chemotherapy shows no survival benefits in stage II dMMR colon cancers, either with or without high-risk factors.


Subject(s)
Brain Neoplasms , Colonic Neoplasms , Colorectal Neoplasms , DNA Mismatch Repair , Neoplastic Syndromes, Hereditary , Humans , Retrospective Studies , Oxaliplatin/therapeutic use , Neoplasm Staging , Carcinoembryonic Antigen , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Colonic Neoplasms/drug therapy , Colonic Neoplasms/genetics , Colonic Neoplasms/surgery , Prognosis , Chemotherapy, Adjuvant
6.
Cancer Med ; 12(21): 20626-20638, 2023 11.
Article in English | MEDLINE | ID: mdl-37881109

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies, and early detection plays a crucial role in enhancing curative outcomes. While colonoscopy is considered the gold standard for CRC diagnosis, noninvasive screening methods of DNA methylation biomarkers can improve the early detection of CRC and precancerous lesions. METHODS: Bioinformatics and machine learning methods were used to evaluate CRC-related genes within the TCGA database. By identifying the overlapped genes, potential biomarkers were selected for further validation. Methylation-specific PCR (MSP) was utilized to identify the associated genes as biomarkers. Subsequently, a real-time PCR assay for detecting the presence of neoplasia or cancer of the colon or rectum was established. This screening approach involved the recruitment of 978 participants from five cohorts. RESULTS: The genes with the highest specificity and sensitivity were Septin9, AXL4, and SDC2. A total of 940 participants were involved in the establishment of the final PCR system and the subsequent performance evaluation test. A multiplex TaqMan real-time PCR system has been illustrated to greatly enhance the ability to detect precancerous lesions and achieved an accuracy of 87.8% (95% CI 82.9-91.5), a sensitivity of 82.7% (95% CI 71.8-90.1), and a specificity of 90.1% (95% CI 84.3-93.9). Moreover, the detection rate of precancerous lesions of this assay reached 55.0% (95% CI 38.7-70.4). CONCLUSION: The combined detection of the methylation status of SEPT9, SDC2, and ALX4 in plasma holds the potential to further enhance the sensitivity of CRC detection.


Subject(s)
Colorectal Neoplasms , Precancerous Conditions , Humans , DNA Methylation , Biomarkers, Tumor/genetics , Sensitivity and Specificity , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Early Detection of Cancer/methods , Cytoskeletal Proteins/genetics , Precancerous Conditions/diagnosis , Precancerous Conditions/genetics
7.
Clin Colon Rectal Surg ; 36(6): 369-377, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37795465

ABSTRACT

Lynch syndrome (LS), caused by germline mutations in the mismatch repair genes, is the most common hereditary colorectal cancer. While LS is also associated with various cancers, early detection of the proband is meaningful for tumor prevention, treatment, and familial management. It has been a dramatic shift on the screening approaches for LS. As the rapid development of the molecular biological methods, a comprehensive understanding of the LS screening strategies will help to improve the clinical care for this systematic disease. The current screening strategies have been well validated but mainly by evidence derived from western population, lacking consideration of the ethnic heterogeneity, which hampers the universality and clinical application in China. Hence, this review will focus on the Chinese experience in LS screening, aiming to help better understand the ethnic diversity and further optimize the screening strategies.

8.
Biochem Pharmacol ; 217: 115829, 2023 11.
Article in English | MEDLINE | ID: mdl-37748664

ABSTRACT

Mesenchymal stem cells (MSCs) and their derived extracellular vesicles (EVs) have emerged as promising tools for promoting bone regeneration. This study investigates the functions of EVs derived from bone marrow-derived MSCs (BMSCs) in osteoporosis (OP) and the molecular mechanism. EVs were isolated from primary BMSCs in mice. A mouse model with OP was induced by ovariectomy. Treatment with EVs restored bone mass and strength, attenuated trabecular bone loss and cartilage damage, and increased osteogenesis while suppressing osteoclastogenesis in ovariectomized mice. In vitro, the EVs treatment improved the osteogenic differentiation of MC-3T3 while inhibiting osteoclastic differentiation of RAW264.7 cells. Microarray analysis revealed a significant upregulation of ubiquitin specific peptidase 7 (USP7) expression in mouse bone tissues following EV treatment. USP7 was found to interact with Yes1 associated transcriptional regulator (YAP1) and stabilize YAP1 protein through deubiquitination modification. YAP1-related genes were enriched in the Wnt/ß-catenin signaling, and overexpression of YAP1 promoted the nuclear translocation of ß-catenin. Functional experiments underscored the critical role of maintaining USP7, YAP1, and ß-catenin levels in the pro-osteogenic and anti-osteoclastogenic properties of the BMSC-EVs. In conclusion, this study demonstrates that USP7, delivered by BMSC-derived EVs, stabilizes YAP1 protein, thereby ameliorating bone formation in OP through the Wnt/ß-catenin activation.


Subject(s)
Extracellular Vesicles , Mesenchymal Stem Cells , Osteoporosis , Animals , Female , Mice , beta Catenin/metabolism , Bone Marrow Cells/metabolism , Cell Differentiation , Extracellular Vesicles/metabolism , Mesenchymal Stem Cells/metabolism , Osteogenesis/genetics , Osteoporosis/metabolism , Protein Stability , Ubiquitin-Specific Peptidase 7/genetics , Up-Regulation , Wnt Signaling Pathway
9.
Nature ; 621(7980): 711-715, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37758892

ABSTRACT

The nearby radio galaxy M87 offers a unique opportunity to explore the connections between the central supermassive black hole and relativistic jets. Previous studies of the inner region of M87 revealed a wide opening angle for the jet originating near the black hole1-4. The Event Horizon Telescope resolved the central radio source and found an asymmetric ring structure consistent with expectations from general relativity5. With a baseline of 17 years of observations, there was a shift in the jet's transverse position, possibly arising from an 8- to 10-year quasi-periodicity3. However, the origin of this sideways shift remains unclear. Here we report an analysis of radio observations over 22 years that suggests a period of about 11 years for the variation in the position angle of the jet. We infer that we are seeing a spinning black hole that induces the Lense-Thirring precession of a misaligned accretion disk. Similar jet precession may commonly occur in other active galactic nuclei but has been challenging to detect owing to the small magnitude and long period of the variation.

10.
Int J Mol Sci ; 24(16)2023 Aug 18.
Article in English | MEDLINE | ID: mdl-37629123

ABSTRACT

Polygonatum cyrtonema (P. cyrtonema) is a valuable rhizome-propagating traditional Chinese medical herb. Polysaccharides (PCPs) are the major bioactive constituents in P. cyrtonema. However, the molecular basis of PCP biosynthesis in P. cyrtonema remains unknown. In this study, we measured the PCP contents of 11 wild P. cyrtonema germplasms. The results showed that PCP content was the highest in Lishui Qingyuan (LSQY, 11.84%) and the lowest in Hangzhou Lin'an (HZLA, 7.18%). We next analyzed the transcriptome profiles of LSQY and HZLA. Through a qRT-PCR analysis of five differential expression genes from the PCP biosynthesis pathway, phosphomannomutase, UDP-glucose 4-epimerase (galE), and GDP-mannose 4,6-dehydratase were determined as the key enzymes. A protein of a key gene, galE1, was localized in the chloroplast. The PCP content in the transiently overexpressed galE1 tobacco leaves was higher than in the wild type. Moreover, luciferase and Y1H assays indicated that PcWRKY31 and PcWRKY34 could activate galE1 by binding to its promoter. Our research uncovers the novel regulatory mechanism of PCP biosynthesis in P. cyrtonema and is critical to molecular-assisted breeding.


Subject(s)
Polygonatum , Polygonatum/genetics , Carbohydrate Metabolism , Gene Expression Profiling , Biological Assay , Chloroplasts
11.
Eur J Cancer ; 192: 113253, 2023 10.
Article in English | MEDLINE | ID: mdl-37625240

ABSTRACT

BACKGROUND: Programmed death-1 (PD-1) inhibitor is effective for colorectal cancer (CRC) with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H). We aimed to explore its effects on CRCs and colonic polyps in Lynch syndrome (LS) patients. METHODS: LS patients with CRC who had evaluable tumours and received at least 2 cycles of PD-1 inhibitors were retrospectively included. PD-1 inhibitors were given as a monotherapy or in combination with other therapies, including anticytotoxic T-lymphocyte-associated antigen-4 treatment, radiotherapy, chemotherapy, and targeted therapy. Correlations of treatment responses with clinicopathological characteristics and genomic profiles were analysed. RESULTS: A total of 75 LS patients were included, with a median age of 39 years. The median duration of follow-up was 27 months (range, 3-71). The objective response rate (ORR) was 70.7%, including 28.0% (n = 21) complete responses and 42.7% (n = 32) partial responses. Four of five cases of LS CRCs displaying proficient MMR (pMMR) or microsatellite stable (MSS) were not responsive. Mucinous/signet-ring cell differentiation was associated with a lower ORR (P = 0.013). The 3-year overall survival and progression-free survival were 91.2% and 82.2%, respectively. A polyp was detected in 26 patients during surveillance. Seven adenomas disappeared after treatment, and they were all larger than 7 mm. CONCLUSION: PD-1 inhibitors are highly effective for dMMR and MSI-H LS CRCs, but not for pMMR or MSS LS CRCs or mucinous/signet-ring cell CRC. Large LS adenomas may also be eliminated by anti-PD-1 treatment. DATA AVAILABILITY STATEMENT: Due to the privacy of patients, the related data cannot be available for public access but can be obtained from Pei-Rong Ding (dingpr@sysucc.org.cn) upon reasonable request. The key raw data have been uploaded to the Research Data Deposit public platform (www.researchdata.org.cn).


Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis , Colorectal Neoplasms , Humans , Adult , Colorectal Neoplasms, Hereditary Nonpolyposis/drug therapy , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Immune Checkpoint Inhibitors , Retrospective Studies , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , DNA Mismatch Repair , Microsatellite Instability
12.
3D Print Addit Manuf ; 10(4): 711-722, 2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37609587

ABSTRACT

The finite element (FE) method is used to characterize the thermal gradient, solidification rate, and molten pool sizes of Ti-6Al-4V plates in the process of selective laser melting (SLM). The results are verified by using the computational fluid dynamics (CFD) simulation. The proposed FE model contains a series of toolpath information that is directly converted from a G-code file, including hatch spacing, laser power, layer thickness, dwell time, and scanning speed generated by using Slic3r software from a CAD file. A proposed multi-layer, multi-track FE model is used to investigate the influence of the laser power, scanning speed, and scanning path on the microstructure in the Ti-6Al-4V plate built via SLM. The processing window is also determined based on the proposed FE model. The FE results indicate that, with a decrease in the laser power and an increase in the scanning speed, the morphology of the crystal grains, showing fully columnar crystals, gradually deviates from the fully equiaxed region. The formed grains are dependent on the laser power, scanning speed, and deposition position, but they are not sensitive to the scanning path, and with the deposition from the bottom layer to the top layer, the size of the formed grains is gradually increasing, which shows a good agreement with the experimental results.

13.
J Matern Fetal Neonatal Med ; 36(2): 2250894, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37635092

ABSTRACT

BACKGROUND: Both young and advanced maternal age pregnancies have strong associations with adverse pregnancy outcomes; however, there is limited understanding of how these associations present in an urban environment in China. This study aimed to analyze the associations between maternal age and pregnancy outcomes among Chinese urban women. METHODS: We performed a population-based study consisting of 60,209 singleton pregnancies of primiparous women whose newborns were delivered after 20 weeks' gestation between January 2012 and December 2015 in urban areas of China. Participants were divided into six groups (19 or younger, 20-24, 25-29, 30-34, 35-39, 40 or older). Pregnancy outcomes include gestational diabetes mellitus (GDM), preeclampsia, placental abruption, placenta previa, premature rupture of membrane (PROM), postpartum hemorrhage, preterm birth, low birthweight, small for gestational age (SGA), large for gestational age (LGA), fetal distress, congenital microtia, and fetal death. Logistic regression models were used to assess the role of maternal age on the risk of adverse pregnancy outcomes with women aged 25-29 years as the reference group. RESULTS: The risks of GDM, preeclampsia, placenta previa, and postpartum hemorrhage were decreased for women at a young maternal age and increased for women with advanced maternal age. Both young and advanced maternal age increased the risk of preterm birth and low birthweight. Young maternal age was also associated with increased risk of SGA (aOR 1.64, 95% CI 1.46-1.83) and fetal death (aOR 2.08, 95% CI 1.35-3.20). Maternal age over 40 years elevated the odds of placental abruption (aOR 3.44, 95% CI 1.47-8.03), LGA (aOR 1.47, 95% CI 1.09-1.98), fetal death (aOR 2.67, 95% CI 1.16-6.14), and congenital microtia (aOR 13.92, 95% CI 3.91-49.57). There were positive linear associations between maternal age and GDM, preeclampsia, placental abruption, placenta previa, PROM, postpartum hemorrhage, preterm birth, LGA and fetal distress (all P for linear trend < .05), and a negative linear association between maternal age and SGA (P for linear trend < .001). The analysis of the associations between maternal age and adverse fetal outcomes showed U-shape for preterm birth, low birth weight, SGA, fetal death and congenital microtia (all P for quadratic trend < .001). CONCLUSIONS: Advanced maternal age predisposes women to adverse obstetric outcomes. Young maternal age manifests a bidirectional effect on adverse pregnancy outcomes. The findings may contribute to improving women's antenatal care and management.


Subject(s)
Abruptio Placentae , Congenital Microtia , Diabetes, Gestational , Placenta Previa , Postpartum Hemorrhage , Pre-Eclampsia , Premature Birth , Infant, Newborn , Pregnancy , Female , Humans , Pregnancy Outcome/epidemiology , Premature Birth/epidemiology , Premature Birth/etiology , Fetal Distress , Abruptio Placentae/epidemiology , Abruptio Placentae/etiology , Birth Weight , Maternal Age , Placenta Previa/epidemiology , Postpartum Hemorrhage/epidemiology , Postpartum Hemorrhage/etiology , Retrospective Studies , Placenta , China/epidemiology , Diabetes, Gestational/epidemiology , Fetal Death
14.
Zhongguo Zhong Yao Za Zhi ; 48(7): 1840-1850, 2023 Apr.
Article in Chinese | MEDLINE | ID: mdl-37282959

ABSTRACT

Uridine diphosphate glycosyltransferase(UGT) is a highly conserved protein in plants, which usually functions in secondary metabolic pathways. This study used the Hidden Markov Model(HMM) to screen out members of UGT gene family in the whole genome of Dendrobium officinale, and 44 UGT genes were identified. Bioinformatics was used to analyze the structure, phylogeny, and promoter region components of D. officinale genes. The results showed that UGT gene family could be divided into four subfamilies, and UGT gene structure was relatively conserved in each subfamily, with nine conserved domains. The upstream promoter region of UGT gene contained a variety of cis-acting elements related to plant hormones and environmental factors, indicating that UGT gene expression may be induced by plant hormones and external environmental factors. UGT gene expression in different tissues of D. officinale was compared, and UGT gene expression was found in all parts of D. officinale. It was speculated that UGT gene played an important role in many tissues of D. officinale. Through transcriptome analysis of D. officinale mycorrhizal symbiosis environment, low temperature stress, and phosphorus deficiency stress, this study found that only one gene was up-regulated in all three conditions. The results of this study can help understand the functions of UGT gene family in Orchidaceae plants and provide a basis for further study on the molecular regulation mechanism of polysaccharide metabolism pathway in D. officinale.


Subject(s)
Dendrobium , Mycorrhizae , Dendrobium/genetics , Plant Growth Regulators , Glycosyltransferases/genetics , Glycosyltransferases/metabolism , Gene Expression Profiling , Phylogeny , Plant Proteins/genetics , Plant Proteins/metabolism
15.
Front Endocrinol (Lausanne) ; 14: 1158969, 2023.
Article in English | MEDLINE | ID: mdl-37234802

ABSTRACT

Background: The prevalence of gestational diabetes mellitus (GDM) and advanced maternal age (AMA, ≥ 35 years) has shown an increasing trend worldwide. This study aimed to evaluate the risk of pregnancy outcomes among younger (20-34 years) and older (≥ 35 years) women with GDM and further analyze the epidemiologic interaction of GDM and AMA on these outcomes. Methods: This historical cohort study included 105 683 singleton pregnant women aged 20 years or older between January 2012 and December 2015 in China. Stratified by maternal age, the associations between GDM and pregnancy outcomes were analyzed by performing logistic regression. Epidemiologic interactions were assessed by using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI) with their 95% confidence intervals (95%CIs). Results: Among younger women, individuals with GDM had a higher risk of all maternal outcomes, preterm birth (relative risk [RR] 1.67, 95%CI 1.50-1.85), low birthweight (RR 1.24, 95%CI 1.09-1.41), large for gestational age (RR 1.51, 95%CI 1.40-1.63), macrosomia (RR 1.54, 95%CI 1.31-1.79), and fetal distress (RR 1.56, 95%CI 1.37-1.77) than those without GDM. Among older women, GDM increased the risk of gestational hypertension (RR 2.17, 95%CI 1.65-2.83), preeclampsia (RR 2.30, 95%CI 1.81-2.93), polyhydramnios (RR 3.46, 95%CI 2.01-5.96), cesarean delivery (RR 1.18, 95%CI 1.10-1.25), preterm birth (RR 1.35, 95%CI 1.14-1.60), large for gestational age (RR 1.40, 95%CI 1.23-1.60), macrosomia (RR 1.65, 95%CI 1.28-2.14) and fetal distress (RR 1.46, 95%CI 1.12-1.90). Additive interactions of GDM and AMA on polyhydramnios and preeclampsia were found, with RERI of 3.11 (95%CI 0.05-6.16) and 1.43 (95%CI 0.09-2.77), AP of 0.51 (95%CI 0.22-0.80) and 0.27 (95%CI 0.07-0.46), and SI of 2.59 (95%CI 1.17-5.77) and 1.49 (95%CI 1.07-2.07), respectively. Conclusion: GDM is an independent risk factor for multiple adverse pregnancy outcomes, and may exert additive interactions with AMA on the risk of polyhydramnios and preeclampsia.


Subject(s)
Diabetes, Gestational , Infant, Newborn, Diseases , Polyhydramnios , Pre-Eclampsia , Premature Birth , Pregnancy , Female , Infant, Newborn , Humans , Aged , Diabetes, Gestational/epidemiology , Pregnancy Outcome/epidemiology , Fetal Macrosomia , Cohort Studies , Premature Birth/epidemiology , Premature Birth/etiology , Maternal Age , Fetal Distress
16.
Nature ; 616(7958): 686-690, 2023 04.
Article in English | MEDLINE | ID: mdl-37100940

ABSTRACT

The nearby radio galaxy M87 is a prime target for studying black hole accretion and jet formation1,2. Event Horizon Telescope observations of M87 in 2017, at a wavelength of 1.3 mm, revealed a ring-like structure, which was interpreted as gravitationally lensed emission around a central black hole3. Here we report images of M87 obtained in 2018, at a wavelength of 3.5 mm, showing that the compact radio core is spatially resolved. High-resolution imaging shows a ring-like structure of [Formula: see text] Schwarzschild radii in diameter, approximately 50% larger than that seen at 1.3 mm. The outer edge at 3.5 mm is also larger than that at 1.3 mm. This larger and thicker ring indicates a substantial contribution from the accretion flow with absorption effects, in addition to the gravitationally lensed ring-like emission. The images show that the edge-brightened jet connects to the accretion flow of the black hole. Close to the black hole, the emission profile of the jet-launching region is wider than the expected profile of a black-hole-driven jet, suggesting the possible presence of a wind associated with the accretion flow.

17.
CNS Neurosci Ther ; 29(10): 2843-2856, 2023 10.
Article in English | MEDLINE | ID: mdl-37081763

ABSTRACT

AIMS: Elamipretide (EPT), a novel mitochondria-targeted peptide, has been shown to be protective in a range of diseases. However, the effect of EPT in spinal cord injury (SCI) has yet to be elucidated. We aimed to investigate whether EPT would inhibit pyroptosis and protect against SCI. METHODS: After establishing the SCI model, we determined the biochemical and morphological changes associated with pyroptosis, including neuronal cell death, proinflammatory cytokine expression, and signal pathway levels. Furthermore, mitochondrial function was assessed with flow cytometry, quantitative real-time polymerase chain reaction, and western blot. RESULTS: Here, we demonstrate that EPT improved locomotor functional recovery following SCI as well as reduced neuronal loss. Moreover, EPT inhibited nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome activation and pyroptosis occurrence and decreased pro-inflammatory cytokines levels following SCI. Furthermore, EPT alleviated mitochondrial dysfunction and reduced mitochondrial reactive oxygen species level. CONCLUSION: EPT treatment may protect against SCI via inhibition of pyroptosis.


Subject(s)
Pyroptosis , Spinal Cord Injuries , Humans , Spinal Cord Injuries/metabolism , Inflammasomes/metabolism , Oligopeptides/metabolism , Oligopeptides/pharmacology , Cytokines/metabolism , Spinal Cord/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
18.
Food Chem ; 421: 136152, 2023 Sep 30.
Article in English | MEDLINE | ID: mdl-37094397

ABSTRACT

Raspberry is used as a medicine food homology species and its polysaccharides are worthy being investigated and developed. In the present study, a novel polysaccharide of unripe raspberry fruits (pRCP) was extracted and characterized. The results show that pRCP was an acidic heteropolysaccharide and its Mw value was 74.86 kDa with a high homogeneity. The main chain of pRCP consisted of â†’ 3,6)-ß-Galp(1 â†’ and â†’ 5)-α-Araf(1→, and its side chain was composed of α-Araf(1 â†’ linked to the C3 position of â†’ 3,6)-ß-Galp(1 â†’. In addition, pRCP supplementation increased the gut microbial diversity and reduced harmful bacteria including Erysipelatoclostridium and Negativibacillus in high-fat diet (HFD)-fed mice. Treatment with pRCP also alleviated HFD-induced colonic inflammation and oxidative stress in mice. These beneficial effects can be transferred to recipient mice by faecal microbiota transplantation from pRCP-treated mice. Therefore, our study suggests that pRCP could be used as a potential prebiotics to improve intestinal health by modulating the gut microbiota.


Subject(s)
Rubus , Mice , Animals , Rubus/chemistry , Fruit/chemistry , Polysaccharides/chemistry , Oxidative Stress , Inflammation/drug therapy , Diet, High-Fat/adverse effects , Mice, Inbred C57BL
19.
Opt Lett ; 48(8): 2142-2145, 2023 Apr 15.
Article in English | MEDLINE | ID: mdl-37058662

ABSTRACT

We report high-power multi-junction vertical-cavity surface-emitting lasers (VCSELs) with a significantly suppressed carrier leakage issue under high injection current and temperature. By carefully optimizing the energy band structure of quaternary AlGaAsSb, we obtained a 12-nm-thick AlGaAsSb electron-blocking layer (EBL) with a high effective barrier height (∼122 meV), a low compressive strain (∼0.99%), and a reduced electronic leakage current. The resulting three-junction (3J) 905 nm VCSEL with the proposed EBL exhibits an improved maximum output power (∼46.4 mW) and power conversion efficiency (PCE; ∼55.4%) during room-temperature operation. Also, it was found from thermal simulation that the optimized device shows more advantages over the original device during high-temperature operation. The type-II AlGaAsSb EBL provided an excellent electron-blocking effect and would be a promising strategy for multi-junction VCSELs to realize high-power applications.

20.
Int J Mol Sci ; 24(4)2023 Feb 14.
Article in English | MEDLINE | ID: mdl-36835208

ABSTRACT

Polygonatum cyrtonema Hua is a traditional Chinese herb propagated using rhizomes, and excessive demand for seedlings and quality deterioration caused by rhizome propagation has highlighted that seed propagation may be an ideal solution to address these issues. However, the molecular mechanisms involved in P. cyrtonema Hua seed germination and emergence stages are not well understood. Therefore, in the present study, we performed transcriptomics combined with hormone dynamics during different seed germination stages, and 54,178 unigenes with an average length of 1390.38 bp (N50 = 1847 bp) were generated. Significant transcriptomic changes were related to plant hormone signal transduction and the starch and carbohydrate pathways. Genes related to ABA(abscisic acid), IAA(Indole acetic acid), and JA(Jasmonic acid) signaling, were downregulated, whereas genes related to ethylene, BR(brassinolide), CTK(Cytokinin), and SA(salicylic acid) biosynthesis and signaling were activated during the germination process. Interestingly, GA biosynthesis- and signaling-related genes were induced during the germination stage but decreased in the emergence stage. In addition, seed germination significantly upregulated the expression of genes associated with starch and sucrose metabolism. Notably, raffinose biosynthesis-related genes were induced, especially during the emergence stage. In total, 1171 transcription factor (TF) genes were found to be differentially expressed. Our results provide new insights into the mechanisms underlying P. cyrtonema Hua seed germination and emergence processes and further research for molecular breeding.


Subject(s)
Polygonatum , Transcriptome , Germination/genetics , Polygonatum/genetics , Seeds/metabolism , Abscisic Acid/metabolism , Hormones/metabolism , Starch/metabolism , Gene Expression Regulation, Plant
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