Renewable Electrochemiluminescence Biosensor Based on Eu-MOGs as a Highly Efficient Emitter and a DNAzyme-Mediated Dual-drive DNA Walker as a Signal Amplifier for Ultrasensitive Detection of miRNA-222.

Herein, novel europium metal-organic gels (Eu-MOGs) with excellent cathode electrochemiluminescence (ECL) emission are first used to construct biosensors for the ultrasensitive detection of miRNA-222. Impressively, N and O elements of organic ligand 2,2':6,2″-terpyridine 4,4',4″-tricarboxylic acid (H3-tctpy) can perfectly coordinate with Eu3+ to form Eu-MOGs, which not only reduce nonradiative transition caused by the intramolecular free rotation of phenyl rings in other MOGs to enhance the ECL signal with extraordinary ECL efficiency as high as 37.2% (vs the [Ru(bpy)3]2+/S2O82- ECL system) but also reinforce ligand-to-metal charge transfer (LMCT) by the strong affinity between Eu3+ and N and O elements to greatly improve the stability of ECL signals. Besides, an improved nucleic acid cascade amplification reaction is developed to greatly raise the conversion efficiency from target miRNA-222 to a DNAzyme-mediated dual-drive DNA walker as output DNA, which can simultaneously shear the specific recognition sites from two directions. In that way, the proposed biosensor can further enhance the detection sensitivity of miRNA-222 with a linear range of 10 aM-1 nM and a detection limit (LOD) of 8.5 aM, which can also achieve an accurate response in cancer cell lysates of MHCC-97L and HeLa. Additionally, the biosensor can be self-regenerated by the folding/unfolding of related triplets with pH changes to simplify experimental operations and reduce the cost. Hence, this work proposed novel MOGs with stable and intense ECL signals for the construction of a renewable ECL biosensor, supplying a reliable detection method in biomarker analysis and disease diagnosis.

Chromosome-level genome provides new insight into the overwintering process of Korla pear (Pyrus sinkiangensis Yu).

Korla pear has a unique taste and aroma and is a breeding parent of numerous pear varieties. It is susceptible to Valsa mali var. pyri, which invades bark wounded by freezing injury. Its genetic relationships have not been fully defined and could offer insight into the mechanism for freezing tolerance and disease resistance. We generated a high-quality, chromosome-level genome assembly for Korla pear via the Illumina and PacBio circular consensus sequencing (CCS) platforms and high-throughput chromosome conformation capture (Hi-C). The Korla pear genome is ~ 496.63 Mb, and 99.18% of it is assembled to 17 chromosomes. Collinearity and phylogenetic analyses indicated that Korla might be derived from Pyrus pyrifolia and that it diverged ~ 3.9-4.6 Mya. During domestication, seven late embryogenesis abundant (LEA), two dehydrin (DHN), and 54 disease resistance genes were lost from Korla pear compared with P. betulifolia. Moreover, 21 LEA and 31 disease resistance genes were common to the Korla pear and P. betulifolia genomes but were upregulated under overwintering only in P. betulifolia because key cis elements were missing in Korla pear. Gene deletion and downregulation during domestication reduced freezing tolerance and disease resistance in Korla pear. These results could facilitate the breeding of novel pear varieties with high biotic and abiotic stress resistance.

Effectiveness of gonadotropin-releasing hormone agonists for ovarian function suppression in premenopausal patients with hormone receptor-positive breast cancer: a retrospective single-center real-world study.

PURPOSE: This study evaluated the effectiveness of ovarian function suppression (OFS) of various gonadotropin-releasing hormone agonists (GnRHa) combined with aromatase inhibitors (AI) in premenopausal patients with hormone receptor-positive (HR-positive) breast cancer. Potential risk factors associated with insufficient OFS were analyzed. PATIENTS AND METHODS: Premenopausal HR-positive breast cancer patients who had received AI with GnRHa were studied retrospectively. Patients were divided into different groups according to monthly or trimonthly GnRHa schedules they received, and the effectiveness of OFS was compared between groups. Insufficient OFS was defined as at least one instance of estradiol ≥ 30 pg/ml. Patient data was gathered from medical records for this comparison. RESULTS: Of the 264 patients enrolled in this study, 117 were administered 3.6 mg of goserelin monthly (goserelin 1 M group), 63 received 3.75 mg of leuprorelin monthly (leuprorelin 1 M group) and 84 were given 11.25 mg of leuprorelin every three months (leuprorelin 3 M group). Overall, 7.20% experienced insufficient OFS. The incidence rates in the three GnRHa depot groups were 7.69%, 6.35%, and 7.14%, respectively, without a significant statistical difference (P = 0.900). Notably, younger patients exhibited a higher likelihood of insufficient OFS [OR = 0.900, 95%CI (0.824-0.982), P = 0.018]. CONCLUSION: Insufficient OFS remains a concern during GnRHa and AI treatment. The effectiveness of the three GnRHa depots commonly used in China seems comparable. Younger patients face a heightened risk of insufficient OFS.

In Situ Defect Engineering of Fe-MIL for Self-Enhanced Peroxidase-Like Activity.

Defect engineering is an effective strategy to enhance the enzyme-like activity of nanozymes. However, previous efforts have primarily focused on introducing defects via de novo synthesis and post-synthetic treatment, overlooking the dynamic evolution of defects during the catalytic process involving highly reactive oxygen species. Herein, a defect-engineered metal-organic framework (MOF) nanozyme with mixed linkers is reported. Over twofold peroxidase (POD)-like activity enhancement compared with unmodified nanozyme highlights the critical role of in situ defect formation in enhancing the catalytic performance of nanozyme. Experimental results reveal that highly active hydroxyl radical (•OH) generated in the catalytic process etches the 2,5-dihydroxyterephthalic acid ligands, contributing to electronic structure modulation of metal sites and enlarged pore sizes in the framework. The self-enhanced POD-like activity induced by in situ defect engineering promotes the generation of •OH, holding promise in colorimetric sensing for detecting dichlorvos. Utilizing smartphone photography for RGB value extraction, the resultant sensing platform achieves the detection for dichlorvos ranging from 5 to 300 ng mL-1 with a low detection limit of 2.06 ng mL-1. This pioneering work in creating in situ defects in MOFs to improve catalytic activity offers a novel perspective on traditional defect engineering.

Effect of high-fat diet on the fatty acid profiles of brain in offspring mice exposed to maternal gestational diabetes mellitus.

OBJECTIVE: Fatty acids play a critical role in the proper functioning of the brain. This study investigated the effects of a high-fat (HF) diet on brain fatty acid profiles of offspring exposed to maternal gestational diabetes mellitus (GDM). METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish the GDM animal model. Brain fatty acid profiles of the offspring mice were measured by gas chromatography at weaning and adulthood. Protein expressions of the fatty acid transport pathway Wnt3/ß-catenin and the target protein major facilitator superfamily domain-containing 2a (MFSD2a) were measured in the offspring brain by Western blot. RESULTS: Maternal GDM increased the body weight of male offspring (P < 0.05). In weaning offspring, factorial analysis showed that maternal GDM increased the monounsaturated fatty acid (MUFA) percentage of the weaning offspring's brain (P < 0.05). Maternal GDM decreased offspring brain arachidonic acid (AA), but HF diet increased brain linoleic acid (LA) (P < 0.05). Maternal GDM and HF diet reduced offspring brain docosahexaenoic acid (DHA), and the male offspring had higher DHA than the female offspring (P < 0.05). In adult offspring, factorial analysis showed that HF diet increased brain MUFA in offspring, and male offspring had higher brain MUFA than female offspring (P < 0.05). The HF diet increased brain LA in the offspring. Male offspring had higher level of AA than female offspring (P < 0.05). HF diet reduced DHA in the brains of female offspring. The brain protein expression of ß-catenin and MFSD2a in both weaning and adult female offspring was lower in the HF + GDM group than in the CON group (P < 0.05). CONCLUSIONS: Maternal GDM increased the susceptibility of male offspring to HF diet-induced obesity. HF diet-induced adverse brain fatty acid profiles in both male and female offspring exposed to GDM.

Effective microorganism combinations improve the quality of compost-bedded pack products in heifer barns: exploring pack bacteria-fungi interaction mechanisms.

BACKGROUND: Compost-bedded pack barns (CBP) are getting huge attention as an alternative housing system for dairy cows due to their beneficial impact on animal welfare. Effective microorganisms (EM) inoculums are believed to enhance compost quality, improve soil structure and benefit the environment. However, little information is available on the impact of incubation with external EM combinations on the barn environment, compost quality and microbial diversity in CBP. This experiment was carried out to investigate the effect of inoculating different combinations of EM [Lactobacillus plantarum (L), Compound Bacillus (B) and Saccharomyces cerevisiae (S)] on compost quality and microbial communities of CBP products, as well as the relationship with the heifers' barn environment. CBP barns were subjected to the following four treatments: CON with no EM inoculum, LB/LS/LBS were Incubated with weight ratios of 1:2 (L: B), 1:2 (L: S), 1:1:1 (L: B: S), respectively. RESULTS: The EM inoculation (LB, LS, LBS) reduced the concentration of respirable particulate matter (PM10 and PM2.5) in the CBP, and decreased the serum total protein and total cholesterol levels in heifers. Notably, LBS achieved the highest content of high-density lipoprotein compared to other treatments. Microbiome results revealed that EM inoculation reduced the bacterial abundance (Chao1 index) and fungal diversity (Shannon & Simpson indexes), while increasing the relative abundance of various bacterial genera (Pseudomonas, Paracoccus, Aequorivita) and fungi (Pestalotiopsis), which are associated with cellulose decomposition that ultimately resulted in accelerating organic matter degradation and humification. Furthermore, high nutrient elements (TK&TP) and low mycotoxin content were obtained with EM inoculation, with LBS showing a particularly pronounced effect. Meanwhile, LBS contributed to a decline in the proportion of fungal pathogen categories but also led to an increase in fungal saprotroph categories. CONCLUSION: Generally, EM inoculation positively impacted compost product quality as organic fertilizer and barn environment by modifying the abundance of cellulolytic bacteria and fungi, while inhibiting the reproduction of pathogenic microbes, especially co-supplementing with L, B and S achieved an amplifying effect.

Ultrahigh extinction ratio and a low power silicon thermo-optic switch.

The silicon thermo-optic switch (TOS) is one of the most fundamental and crucial blocks in large-scale silicon photonic integrated circuits (PICs). An energy-efficient silicon TOS with ultrahigh extinction ratio can effectively mitigate cross talk and reduce power consumption in optical systems. In this Letter, we demonstrate a silicon TOS based on cascading Mach-Zehnder interferometers (MZIs) with spiral thermo-optic phase shifters. The experimental results show that an ultrahigh extinction ratio of 58.8 dB is obtained, and the switching power consumption is as low as 2.32 mW/π without silicon air trench. The rise time and fall time of the silicon TOS are about 10.8 and 11.2 µs, respectively. Particularly, the figure of merit (FOM) has been improved compared with previously reported silicon TOS. The proposed silicon TOS may find potential applications in optical switch arrays, on-chip optical delay lines, etc.

Gestational Diabetes Mellitus Remodels the Fetal Brain Fatty Acid Profile Through Placenta-Brain Lipid Axis in C57BL/6J Mice.

BACKGROUND: Polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), are critical for proper fetal brain growth and development. Gestational diabetes mellitus (GDM) could affect maternal-fetal fatty acid metabolism. OBJECTIVE: This study aimed to explore the effect of GDM and high-fat (HF) diet on the DHA transport signaling pathway in the placenta-brain axis and fatty acid concentrations in the fetal brain. METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish an animal model of GDM. Eighty female C57BL/6J mice were randomly divided into control (CON), GDM, HF, and HF+GDM groups. The fatty acid profiles of the maternal liver and fetal brain were analyzed by gas chromatography. In addition, we analyzed the protein amounts of maternal liver fatty acid desaturase (FADS1/3), elongase (ELOVL2/5) and the regulatory factor sterol-regulatory element-binding protein (SREBP)-1c, and the DHA transport signaling pathway (Wnt3/ß-catenin/MFSD2a) of the placenta and fetal brain using western blotting. RESULTS: GDM promoted the decrease of maternal liver ELOVL2, ELOVL5, and SREBP-1c. Accordingly, we observed a significant decrease in the amount of maternal liver arachidonic acid (AA), DHA, and total n-3 PUFA and n-6 PUFA induced by GDM. GDM also significantly decreased the amount of DHA and n-3 PUFA in the fetal brain. GDM downregulated the Wnt3/ß-catenin/MFSD2a signaling pathway, which transfers n-3 PUFA in the placenta and fetal brain. The HF diet increased n-6 PUFA amounts in the maternal liver, correspondingly increasing linoleic acid, gamma-linolenic acid, AA, and total n-6 PUFA in the fetal brain, but decreased DHA amount in the fetal brain. However, HF diet only tended to decrease placental ß-catenin and MFSD2a amounts (P = 0.074 and P = 0.098, respectively). CONCLUSIONS: Maternal GDM could affect the fatty acid profile of the fetal brain both by downregulating the Wnt3/ß-catenin/MFSD2a pathway of the placental-fetal barrier and by affecting maternal fatty acid metabolism.

Multi-center study of COVID-19 infection in elderly patients with lymphoma: on behalf of Jiangsu Cooperative Lymphoma Group (JCLG).

Elderly patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we retrospectively described the clinical features and outcomes of the first time infection of Omicron SARS-CoV-2 in 364 elderly patients with lymphoma enrolled in Jiangsu Cooperative Lymphoma Group (JCLG) between November 2022 and April 2023 in China. Median age was 69 years (range 60-92). 54.4% (198/364) of patients were confirmed as severe and critical COVID-19 infection. In univariable analysis, Age > 70 years (OR 1.88, p = 0.003), with multiple comorbidities (OR 1.41, p = 0.005), aggressive lymphoma (OR 2.33, p < 0.001), active disease (progressive or relapsed/refractory, OR 2.02, p < 0.001), and active anti-lymphoma therapy (OR 1.90, p < 0.001) were associated with severe COVID-19. Multiple (three or more) lines of previous anti-lymphoma therapy (OR 3.84, p = 0.021) remained an adverse factor for severe COVID-19 in multivariable analysis. Moreover, CD20 antibody (Rituximab or Obinutuzumab)-based treatments within the last 6 months was associated with severe COVID-19 in the entire cohort (OR 3.42, p < 0.001). Continuous BTK inhibitors might be protective effect on the outcome of COVID-19 infection (OR 0.44, p = 0.043) in the indolent lymphoma cohort. Overall, 7.7% (28/364) of the patients ceased, multiple lines of previous anti-lymphoma therapy (OR 3.46, p = 0.016) remained an adverse factor for mortality.

LINC00894 Regulates Cerebral Ischemia/Reperfusion Injury by Stabilizing EIF5 and Facilitating ATF4-Mediated Induction of FGF21 and ACOD1 Expression.

The non-coding RNA LINC00894 modulates tumor proliferation and drug resistance. However, its role in brain is still unclear. Using RNA-pull down combined with mass spectrometry and RNA binding protein immunoprecipitation, EIF5 was identified to interact with LINC00894. Furthermore, LINC00894 knockdown decreased EIF5 protein expression, whereas LINC00894 overexpression increased EIF5 protein expression in SH-SY5Y and BE(2)-M17 (M17) neuroblastoma cells. Additionally, LINC00894 affected the ubiquitination modification of EIF5. Adeno-associated virus (AAV) mediated LINC00894 overexpression in the brain inhibited the expression of activated Caspase-3, while increased EIF5 protein level in rats and mice subjected to transient middle cerebral artery occlusion reperfusion (MCAO/R). Meanwhile, LINC00894 knockdown increased the number of apoptotic cells and expression of activated Caspase-3, and its overexpression decreased them in the oxygen-glucose deprivation and reoxygenation (OGD/R) in vitro models. Further, LINC00894 was revealed to regulated ATF4 protein expression in condition of OGD/R and normoxia. LINC00894 knockdown also decreased the expression of glutamate-cysteine ligase catalytic subunit (GCLC) and ATF4, downregulated glutathione (GSH), and the ratio of GSH to oxidized GSH (GSH: GSSG) in vitro. By using RNA-seq combined with qRT-PCR and immunoblot, we identified that fibroblast growth factor 21 (FGF21) and aconitate decarboxylase 1 (ACOD1), as the ATF4 target genes were regulated by LINC00894 in the MCAO/R model. Finally, we revealed that ATF4 transcriptionally regulated FGF21 and ACOD1 expression; ectopic overexpression of FGF21 or ACOD1 in LINC00894 knockdown cells decreased activated Caspase-3 expression in the OGD/R model. Our results demonstrated that LINC00894 regulated cerebral ischemia injury by stabilizing EIF5 and facilitating EIF5-ATF4-dependent induction of FGF21 and ACOD1.

Minocycline alleviates microglia ferroptosis by inhibiting HO-1 during cerebral ischemia-reperfusion injury.

OBJECTIVE: Ischemic stroke is a leading cause of death and disability in individuals worldwide. Cerebral ischemia-reperfusion injury (CIRI) typically results in severe secondary injury and complications following reperfusion therapy. Microglia play critical roles in the inflammatory reaction of CIRI. However, less attention has been given to microglial death in this process. Our study aims to explore microglial death in CIRI and the effects and mechanism of minocycline treatment on microglia. METHODS: A middle cerebral artery occlusion (MCAO) model was applied to induce CIRI in rats. At 0 h, 24 h and 48 h post-operation, rats were intraperitoneally injected with 45 mg/kg minocycline. Neurological deficit scoring, 2,3,5-triphenyltetrazolium chloride (TTC) staining, assessment of activated microglia and examination of mitochondrial structure were conducted and checked at 72 h after reperfusion. Additionally, an in vitro model of oxygen-glucose deprivation/reperfusion (OGD/R) model was established. BV-2 cells were treated with various pharmacological inhibitors of cell death or minocycline. Cell viability, lipid peroxidation, mitochondrial structure and function, and labile Fe2+ and ferroptosis-associated gene/protein levels were measured. Hemin was used for further validation after transcriptome analysis. RESULTS: In the MCAO and OGD/R models, ferroptosis was identified as a major form of microglial death. Minocycline inhibited microglia ferroptosis by reducing HO-1 expression. In addition, minocycline improved mitochondrial membrane potential, mitochondrial structures and microglial survival in vivo. Minocycline also decreased labile Fe2+ levels, lipid peroxidation, and expression of ferritin heavy chain (FTH) and it improved mitochondrial structure and function in vitro. Upregulation of HO-1 counteracted the protective effect of minocycline. CONCLUSION: Ferroptosis is a major form of microglial death in CIRI. The protective mechanism of minocycline in CIRI partially hinges on its ability to effectively ameliorate microglia ferroptosis by downregulating HO-1 expression. Consequently, targeting microglia ferroptosis is a promising treatment for CIRI.

Optical Information Transmission and Multimode Fluorescence Anticounterfeiting of Ca2-xMgxGe7O16:Mn2.

Multimode emission of Mn2+ for multimode fluorescence anticounterfeiting is achieved by cation site and interstitial occupancy in Ca2-xMgxGe7O16. The rings in Ca2-xMgxGe7O16 have a significant distortion for Mn2+ ions to enter the ring interstitials with a luminescence center at 665 nm, which is supported by XRD refinement results and first-principles calculations. The interstitial Mn2+ ion has good thermal stability with an activation energy of 0.36 eV. Surprisingly, these two luminescence centers, the cation site Mn and the interstitial Mn, have an obvious afterglow, and the disappearing afterglow will reappear by heating or irradiating with the 980 nm laser. The afterglow is significantly enhanced, as MnO2 is used as the manganese source, which is explained in detail by the thermal luminescence spectrum. Finally, Ca2-xMgxGe7O16:Mn2+ fully demonstrates its excellent prospects in fluorescent anticounterfeiting, information encryption, and optical information storage.

Glutamine Protects against Mouse Abdominal Aortic Aneurysm through Modulating VSMC Apoptosis and M1 Macrophage Activation.

Glutamine (Gln), known as the most abundant free amino acid, is widely spread in human body. In this study, we demonstrated the protective effects of glutamine against mouse abdominal aortic aneurysm (AAA) induced by both angiotensin II (AngII) and calcium phosphate (Ca3(PO4)2) in vivo, which was characterized with lower incidence of mouse AAA. Moreover, histomorphological staining visually presented more intact elastic fiber and less collagen deposition in abdominal aortas of mice treated by glutamine. Further, we found glutamine inhibited the excessive production of reactive oxide species (ROS), activity of matrix metalloproteinase (MMP), M1 macrophage activation, and apoptosis of vascular smooth muscle cells (VSMCs) in suprarenal abdominal aortas of mice, what's more, the high expressions of MMP-2 protein, MMP-9 protein, pro-apoptotic proteins, and IL-6 as well as TNF-α in protein and mRNA levels in cells treated by AngII were down-regulated by glutamine. Collectively, these results revealed that glutamine protected against mouse AAA through inhibiting apoptosis of VSMCs, M1 macrophage activation, oxidative stress, and extracellular matrix degradation.

The effect of acute sleep deprivation on cortisol level: a systematic review and meta-analysis.

Acute sleep deprivation has aroused widespread concern and the relationship between acute sleep deprivation and cortisol levels is inconsistent. This study aimed to explore additional evidence and details. The PubMed, Web of Science, EMBASE, CLINAHL and Cochrane databases were searched for eligible studies published up to June 7, 2023. All analyses were performed using Review Manager 5.4 and Stata/SE 14.0. A total of 24 studies contributed to this meta-analysis. There was no significant difference in cortisol levels between participants with acute sleep deprivation and normal sleep in 21 crossover-designed studies (SMD = 0.18; 95% CI: -0.11, 0.45; p = 0.208) or 3 RCTs (SMD = 0.26; 95% CI: -0.22, 0.73; p = 0.286). Subgroup analysis revealed that the pooled effects were significant for studies using serum as the sample (SMD = 0.46; 95%CI: 0.11, 0.81; p = 0.011). Studies reporting cortisol levels in the morning, in the afternoon and in the evening did not show significant difference (p > 0.05). The pooled effects were statistically significant for studies with multiple measurements (SMD = 0.28; 95%CI: 0.03, 0.53; p = 0.027) but not for studies with single cortisol assessments (p = 0.777). When the serum was used as the test sample, the cortisol levels of individuals after acute sleep deprivation were higher than those with normal sleep.

Trajectories of depressive symptom and its association with air pollution: evidence from the Mr. OS and Ms. OS Hong Kong cohort study.

BACKGROUND: Depression is a global health priority. Maintaining and delaying depressive symptoms in older adults is a key to healthy aging. This study aimed to identify depressive symptom trajectories, predictors and mortality, while also exploring the relationship between air quality and depressive symptoms in older adults in the Hong Kong community over 14 years. METHODS: This study is a longitudinal study in Hong Kong. The target population was community-dwelling older adults over age 65. Depressive symptoms were measured by the Geriatric Depression Scale (GDS-15). Group-based trajectory model was used to identify heterogeneity in longitudinal changes over 14 years and examine the associations between baseline variables and trajectories for different cohort members using multinomial logistic regression. The Kaplan-Meier method was employed to conduct survival analysis and explore the variations in survival probabilities over time among different trajectory group. Linear mixed model was used to explore the relationship between air quality and depressive symptoms. RESULTS: A total of 2828 older adults were included. Three different trajectories of depressive symptoms in older people were identified: relatively stable (15.4%), late increase (67.1%) and increase (17.5%). Female, more number of chronic diseases, poor cognitive function, and poor health-related quality of life (HRQOL) were significantly associated with other less favorable trajectories compared with participants with stable levels of depressive symptoms. The late increase group had a lower mortality rate than the relatively stable and increased groups. Lower baseline ambient air pollutant exposure to NO2 over 14 years was significantly associated with fewer depressive symptoms. CONCLUSIONS: In this study, we found that a late increase in depressive symptoms was the predominant trend in older Chinese people in Hong Kong. Poorer HRQOL was predictive of less favorable trajectories of depressive symptoms. Ambient air pollution was associated with depressive symptoms. This novel observation strengthens the epidemiological evidence of longitudinal changes in depressive symptoms and associations with late-life exposure to air pollution.

Pathogenic recurrent copy number variants in 7,078 pregnancies via chromosomal microarray analysis.

OBJECTIVES: To investigate the incidence of pathogenic recurrent CNVs in fetuses with different referral indications and review the intrauterine phenotypic features of each CNV. METHODS: A total of 7,078 amniotic fluid samples were collected for chromosome microarray analysis (CMA) and cases carrying pathogenic recurrent CNVs were further studied. RESULTS: The highest incidence of pathogenic recurrent CNVs was 2.25 % in fetal ultrasound anomalies (FUA) group. Moreover, regardless of other indications, pregnant women with advanced maternal age have a lower incidence compared with whom less than 35 years old (p<0.05). In total 1.17 % (83/7,078) samples carried pathogenic recurrent CNVs: 20 cases with 22q11.2 recurrent region (12 microdeletion and eight microduplication), 11 with 1q21.1 (five microdeletion and six microduplication) and 16p13.11 (four microdeletion and seven microduplication), 10 with 15q11.2 recurrent microdeletion, seven with Xp22.31 recurrent microdeletion and 16p11.2 (three microdeletion and four microduplication), four with 7q11.23 (two microdeletion and two microduplication), three with 17p11.2 (three microdeletion), 17p12 (two microdeletion and one microduplication) and 17q12 (two microdeletion and one microduplication). The rest ones were rare in this study. CONCLUSIONS: Pathogenic recurrent CNVs are more likely to be identified in FUA group. Pregnant women with advanced maternal age have a lower incidence of pathogenic recurrent CNVs. The profile of pathogenic recurrent CNVs between prenatal and postnatal is different, especially in 22q11.2, 1q21.1, 15q13.3 recurrent region and 15q11.2 deletion.

Effects of postweaning cadmium exposure on socioemotional behaviors in adolescent male mice.

Exposure to cadmium (Cd), a toxic heavy metal classified as an environmental endocrine disruptor, can exert significant toxicity in both animals and humans. However, the potential effects of Cd exposure on socioemotional behaviors are still poorly understood, as are the underlying mechanisms. In the present study, employing a series of behavioral tests as well as 16 S rRNA sequencing analysis, we investigated the long-term effects of Cd exposure on socioemotional behaviors and their associated mechanisms in mice based on the brain-gut interaction theory. The results showed that postweaning exposure to Cd reduced the ability to resist depression, decreased social interaction, subtly altered sexual preference, and changed the composition of the gut microbiota in male mice during adolescence. These findings provided direct evidence for the deleterious effects of exposure to Cd in the postweaning period on socioemotional behaviors later in adolescence, and suggested that these effects of Cd exposure may be linked to changes in the gut microbiota.

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke: The MARVEL Randomized Clinical Trial.

Importance: It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023. Interventions: Eligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures: The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance: Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability. Trial Registration: ChiCTR.org.cn Identifier: ChiCTR2100051729.

Intrinsic capacity trajectories, predictors and associations with care dependence in community-dwelling older adults: A social determinant of health perspective.

AIMS: To identify intrinsic capacity trajectories, predictors of intrinsic capacity trajectories and associations between intrinsic capacity trajectories and care dependence in community-dwelling older adults in China. METHODS: A retrospective longitudinal study was conducted, and the data were obtained from a five-year national longitudinal cohort study of older adults in China between 2011 and 2015. The social determinants of health framework informed the data analysis and interpretation. RESULTS: A total of 3893 older adults met the selection criteria and were included in the study. Three intrinsic capacity trajectories were identified: high trajectory (15.7 %), stable trajectory (52.7 %) and declining trajectory (31.6 %). Social determinants contribute to intrinsic capacity decline in older adults. Decreased cognitive function, psychological status, and locomotion at baseline were associated with care dependence. CONCLUSION: Approximately thirty percent of the older adults in this cohort study experienced a decline in intrinsic capacity within a 5-year period. Social determinants contributed to this decline in older adults.

Functional study of the soybean stamen-preferentially expressed gene GmFLA22a in regulating male fertility.

China has a high dependence on soybean imports, yield increase at a faster rate is an urgent problem that need to be solved at present. The application of heterosis is one of the effective ways to significantly increase crop yield. In recent years, the development of an intelligent male sterility system based on recessive nuclear sterile genes has provided a potential solution for rapidly harnessing the heterosis in soybean. However, research on male sterility genes in soybean has been lagged behind. Based on transcriptome data of soybean floral organs in our research group, a soybean stamen-preferentially expressed gene GmFLA22a was identified. It encodes a fasciclin-like arabinogalactan protein with the FAS1 domain, and subcellular localization studies revealed that it may play roles in the endoplasmic reticulum. Take advantage of the gene editing technology, the Gmfla22a mutant was generated in this study. However, there was a significant reduction in the seed-setting rate in the mutant plants at the reproductive growth stage. The pollen viability and germination rate of Gmfla22a mutant plants showed no apparent abnormalities. Histological staining demonstrated that the release of pollen grains in the mutant plants was delayed and incomplete, which may due to the locule wall thickening in the anther development. This could be the reason of the reduced seed-setting rate in Gmfla22a mutants. In summary, our study has preliminarily revealed that GmFLA22a may be involved in regulating soybean male fertility. It provides crucial genetic materials for further uncovering its molecular function and gene resources and theoretical basis for the utilization of heterosis in soybean.