DL-Serine Hydrazide Hydrochloride Multiple-site Synergy Induced Effective and Stable Formamidine-Rich Perovskite Solar Cells.

The efficiency and stability of solar cells are two key indicators that determine for the commercial feasibility of photovoltaic devices. Formamidine-cesium perovskite has been extensively investigated since its excellent thermal stability and has great potential in achieving high power conversion efficiency. However, during the aging process, especially under light conditions, formamidine-rich perovskites are prone to produce iodine, and the escape of iodine is one of the important factors leading to device degradation. Here, DL-Serine Hydrazide Hydrochloride containing the reducing group is introduced into the precursor solution of formamidine-cesium perovskite, which achieves multiple-site passivation. Hydrazine reacts with iodine to reduce it to iodine ions, inhibiting the escape of iodine. In addition, carbonyl groups and uncoordinated lead ions form coordination bonds to reduce defects. In the end, the perovskite solar cell with DL-Serine Hydrazide Hydrochloride added achieves a champion efficiency of 22.22%, and maintains 85.88% of the initial efficiency after continuous exposure under 1 sun for 7000 s at a relative humidity of ≈40%. Additionally, DL-Serine Hydrazide Hydrochloride added device shows good stability in air environments with relative humidity of 50%-60%. DL-Serine Hydrazide Hydrochloride improves the stability of formamidine-rich perovskite solar cells and provides a low-cost strategy for commercial development.

Rapid electrodeposition of Cu nanoparticle film on Ni foam as an integrated 3D free-standing electrode for non-invasive and non-enzymatic creatinine sensing.

High cost, inherent destabilization, and intricate fixing of enzyme molecules are the main drawbacks of enzyme-based creatinine sensors. The design of a low-cost, stabilizable, and enzyme-free creatinine sensing probe is essential to address these limitations. In this work, an integrated three-dimensional (3D) free-standing electrode was designed to serve as a non-enzymatic creatinine sensing platform and was fabricated by rapid electrodeposition of a dense copper nanoparticle film on nickel foam (Cu NP film/NF). This low-cost, stable, easy-to-fabricate, and binder-free Cu NP film/NF electrode has abundant active sites and excellent electrochemical performance. Cyclic voltammetry measurements show a wide linear range (0.25-24 mM), low detection limit (0.17 mM), and high sensitivity (306 µA mM-1 cm-2). The developed sensor shows high recovery of creatinine concentration in real urine. Besides, it has better specificity, reproducibility, and robustness in detecting creatinine. These excellent results suggest that a non-enzymatic creatinine sensor based on an integrated 3D free-standing Cu NP film/NF electrode has good potential for non-invasive detection of urinary creatinine.

Serum lipid reference values recommended during a twin pregnancy and evaluating its association with perinatal outcomes.

BACKGROUND: Maternal lipid metabolism fluctuations have been shown to increase the risk of adverse pregnancy outcomes. However, there is no consensus over what constitutes normal maternal lipid values during twin pregnancy. Therefore, the aim of this study was to establish a serum lipid reference range for a twin pregnancy. METHODS: A retrospective survey was conducted, from 2011 to 2021, at the Peking University Third Hospital. A total of 881 twin pregnancies, with lipid data from early and middle pregnancies, were included. After excluding those with adverse pregnancy outcomes, we performed a descriptive analysis of total cholesterol (TC), triglycerides (TG), high-density lipid cholesterol (HDL-C), and low-density lipid cholesterol (LDL-C) levels, using the mean and standard deviation to determine appropriate percentiles. We later determined the lipid reference range in early and middle pregnancy based on the initial results. We evaluated Inappropriate lipid levels associations with pregnancy outcomes, including gestational diabetes, pregnancy-induced hypertension, small for gestational age. RESULTS: (1) Serum levels of TC, TG, LDL-C, and HDL-C increased significantly from early to late pregnancy, where the greatest increase was observed in TG. (2) Based on the results, we recommend that TC, TG, and LDL-C serum reference values during early and middle pregnancy should be less than the 95th percentile. On the other hand, HDL-C should be greater than the 5th percentile. During early pregnancy, the values recommended are TC < 5.31 mmol/L, TG < 2.25 mmol/L, HDL > 1.02 mmol/L and LDL < 3.27 mmol/L, and those during middle pregnancy are TC < 8.74 mmol/L, TG < 4.89 mmol/L, HDL > 1.25 mmol/L and LDL < 5.49 mmol/L, while the values during late pregnancy are TC < 9.11 mmol/L, TG < 6.70 mmol/L, HDL > 1.10 mmol/L and LDL < 5.81 mmol/L. Higher levels of blood lipids were associated with GDM, PE, SGA. CONCLUSIONS: We suggested a reference ranges for blood lipids during the twin pregnancy in a Chinese population. The reference ranges recommended by this study can be used to identify women with twin pregnancies using unfavorable lipid values. Higher levels of blood lipids were associated with adverse pregnancy outcomes.

Remarkable nucleation and growth of ultrafine particles from vehicular exhaust.

High levels of ultrafine particles (UFPs; diameter of less than 50 nm) are frequently produced from new particle formation under urban conditions, with profound implications on human health, weather, and climate. However, the fundamental mechanisms of new particle formation remain elusive, and few experimental studies have realistically replicated the relevant atmospheric conditions. Previous experimental studies simulated oxidation of one compound or a mixture of a few compounds, and extrapolation of the laboratory results to chemically complex air was uncertain. Here, we show striking formation of UFPs in urban air from combining ambient and chamber measurements. By capturing the ambient conditions (i.e., temperature, relative humidity, sunlight, and the types and abundances of chemical species), we elucidate the roles of existing particles, photochemistry, and synergy of multipollutants in new particle formation. Aerosol nucleation in urban air is limited by existing particles but negligibly by nitrogen oxides. Photooxidation of vehicular exhaust yields abundant precursors, and organics, rather than sulfuric acid or base species, dominate formation of UFPs under urban conditions. Recognition of this source of UFPs is essential to assessing their impacts and developing mitigation policies. Our results imply that reduction of primary particles or removal of existing particles without simultaneously limiting organics from automobile emissions is ineffective and can even exacerbate this problem.

Outcome of monochorionic triamniotic triplet pregnancies: Expectant management versus fetal reduction.

OBJECTIVE: To compare the outcomes of monochorionic triamniotic (MCTA) triplets managed expectantly with those reduced to twins. METHOD: This was a retrospective cohort study comparing expectant management (EM) with fetal reduction (FR) to twins in 43 consecutive MCTA triplets with 3 live fetuses at 11-14 weeks between 2012 and 2021. RESULTS: Nineteen patients managed expectantly and 24 triplets reduced to twins were included. The rate of pregnancy with at least one survivor was 84.2% in the EM group and 66.7% in the FR group (P = 0.190). Compared to the EM cases, triplets reduced to twins had a higher median gestational age at delivery (36.0 vs. 33.3 weeks; P < 0.001), a higher mean birth weight (2244.3 ± 488.6 g vs. 1751.1 ± 383.2 g; P < 0.001) and a lower risk of preterm birth before 34 weeks (11.8% vs. 64.7%; P = 0.001). There were no significant differences in the risk of miscarriage, pregnancy complications and composite adverse neonatal outcomes. CONCLUSION: In MCTA triplets, FR to twins could reduce the risk of preterm birth, whereas EM seems to be a reasonable choice when the priority is at least one survivor. However, due to the small sample size of this study, these findings must be interpreted with great caution.

Prenatal maternal depressive symptoms of Chinese pregnant women and twin newborns' physical health: the moderating role of infant sex.

Consequences of prenatal maternal depressive symptoms on infant health are well established. But the results of infants' sex differences of such consequences are mixed. The current study examines whether any association exists between prenatal maternal depressive symptoms and infant physical health different for the sex of newborns. A sample of 84 women pregnant with twins reported depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS) in the late gestational stage. The Apgar scores of newborns were assessed by healthcare providers at 1, 5, and 10 minutes after birth. The relationship of maternal prenatal depressive symptoms and newborns' physical health was moderated by infant sex. Higher depressive symptoms were associated with a lower Apgar index among newborn boys but not girls. Fetus environment or biomarkers related to sex may be a key mechanism of the effect of prenatal depression symptoms on newborns' health. Tailored interventions targeting maternal depression symptoms may be warranted.

[Phagocytosis of microglia in neurodegenerative diseases].

With the acceleration of the aging society, neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), have become a rapidly growing global health crisis. Recent studies have indicated that microglia-neuron interactions are critical for maintaining homeostasis of the central nervous system. Genome-Wide Association Studies and brain imaging studies have suggested that microglia are activated in early stage of neurodegenerative diseases. Microglia are specialized phagocytes in the brain. The discovery of a new phagocytic pathway, trogocytosis, suggests that there is a close interaction between microglia and surviving neurons. In this review, we summarize the important roles of microglia in neurodegenerative diseases, and further analyze the functions and molecular mechanisms of microglia phagocytosis and trogocytosis.

Synaptotagmin-11 regulates the functions of caveolae and responds to mechanical stimuli in astrocytes.

Caveolae play crucial roles in intracellular membrane trafficking and mechanosensation. In this study, we report that synaptotagmin-11 (Syt11), a synaptotagmin isoform associated with Parkinson's disease and schizophrenia, regulates both caveolae-mediated endocytosis and the caveolar response to mechanical stimuli in astrocytes. Syt11-knockout (KO) accelerated caveolae-mediated endocytosis. Interestingly, the caveolar structures on the cell surface were markedly fewer in the absence of Syt11. Caveolar disassembly in response to hypoosmotic stimuli and astrocyte swelling were both impaired in Syt11-KO astrocytes. Live imaging revealed that Syt11 left caveolar structures before cavin1 during hypoosmotic stress and returned earlier than cavin1 after isoosmotic recovery. Chronic hypoosmotic stress led to proteasome-mediated Syt11 degradation. In addition, Syt11-KO increased the turnover of cavin1 and EH domain-containing protein 2 (EHD2), accompanied by compromised membrane integrity, suggesting a mechanoprotective role of Syt11. Direct interactions between Syt11 and cavin1 and EHD2, but not caveolin-1, are found. Altogether, we propose that Syt11 stabilizes caveolar structures on the cell surface of astrocytes and regulates caveolar functions under physiological and pathological conditions through cavin1 and EHD2.

Fetal growth velocity references from a Chinese population-based fetal growth study.

BACKGROUND: Fetal growth velocity standards have yet to be established for the Chinese population. This study aimed to establish such standards suitable for the Chinese population. METHODS: We performed a multicenter, population-based longitudinal cohort study including 9075 low-risk singleton pregnant women. Data were collected from the clinical records of 24 hospitals in 18 provinces of China. Demographic characteristics, reproductive history, fetal ultrasound measurements, and perinatal outcome data were collected. The fetal ultrasound measurements included biparietal diameter (BPD), abdominal circumference (AC), head circumference (HC), and femur diaphysis length (FDL). We used linear mixed models with cubic splines to model the trajectory of four ultrasound parameters and estimate fetal weight. Fetal growth velocity was determined by calculating the first derivative of fetal size curves. We also used logistic regression to estimate the association between fetal growth velocities in the bottom 10th percentile and adverse perinatal outcomes. RESULTS: Fetal growth velocity was not consistent over time or among individuals. The estimated fetal weight (EFW) steadily increased beginning at 12 gestational weeks and peaked at 35 gestational weeks. The maximum velocity was 211.71 g/week, and there was a steady decrease in velocity from 35 to 40 gestational weeks. The four ultrasound measurements increased in the early second trimester; BPD and HC peaked at 13 gestational weeks, AC at 14 gestational weeks, and FDL at 15 gestational weeks. BPD and HC also increased from 19 to 24 and 19 to 21 gestational weeks, respectively. EFW velocity in the bottom 10th percentile indicated higher risks of neonatal complications (odds ratio [OR] = 2.23, 95% confidence interval [CI]: 1.79-2.78) and preterm birth < 37 weeks (OR = 3.68, 95% CI: 2.64-5.14). Sensitivity analyses showed that EFW velocity in the bottom 10th percentile was significantly associated with more adverse pregnancy outcomes for appropriate-for-gestational age neonates. CONCLUSIONS: We established fetal growth velocity curves for the Chinese population based on real-world clinical data. Our findings demonstrated that Chinese fetal growth patterns are somewhat different from those of other populations. Fetal growth velocity could provide more information to understand the risk of adverse perinatal outcomes, especially for appropriate-for-gestational age neonates.

CD200 maintains the region-specific phenotype of microglia in the midbrain and its role in Parkinson's disease.

Microglia are a specialized population of tissue macrophages in the mammalian brain. Microglial phenotype is tightly regulated by local environmental factors, although little is known about these factors and their region-preferred roles in regulating local neuroinflammatory responses. We hypothesized that microglia in different brain regions respond differently to neuroinflammatory stimulation and that CD200, an anti-inflammatory protein mainly originated from neurons, acts as a local cue inhibiting microglia activation in the midbrain. We utilized a CD200-deficient mouse line to analyze the phenotypic role of CD200 in the regulation of normal neuron-microglia homeostasis in the midbrain and in the dopaminergic degeneration in an α-synuclein overexpression model of PD. We found that systemic administration of an endotoxin lipopolysaccharide induced a region-preferred change in CD200 expression in the midbrain. Similarly, CD200-/- mice showed a regional preference in an enhancement of microglia activation and baseline inflammatory levels in the midbrain and dopamine neuron loss in the substantia nigra (SN). In a mouse model of Parkinson's disease (PD) induced by rAAV-hSYN injection into the SN, CD200-/- mice showed more dopamine neuron loss in the SN than wild type mice. Activation of CD200 receptors with a CD200 fusion protein alleviated the neuroinflammation and neuronal death in the SN of PD mice. These findings demonstrate that CD200 is essential for the midbrain homeostasis and acts as a critical local regulator in controlling microglial properties related to the PD pathogenesis.

Mutations in C1orf194, encoding a calcium regulator, cause dominant Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease is a hereditary motor and sensory neuropathy exhibiting great clinical and genetic heterogeneity. Here, the identification of two heterozygous missense mutations in the C1orf194 gene at 1p21.2-p13.2 with Charcot-Marie-Tooth disease are reported. Specifically, the p.I122N mutation was the cause of an intermediate form of Charcot-Marie-Tooth disease, and the p.K28I missense mutation predominately led to the demyelinating form. Functional studies demonstrated that the p.K28I variant significantly reduced expression of the protein, but the p.I122N variant increased. In addition, the p.I122N mutant protein exhibited the aggregation in neuroblastoma cell lines and the patient's peroneal nerve. Either gain-of-function or partial loss-of-function mutations to C1ORF194 can specify different causal mechanisms responsible for Charcot-Marie-Tooth disease with a wide range of clinical severity. Moreover, a knock-in mouse model confirmed that the C1orf194 missense mutation p.I121N led to impairments in motor and neuromuscular functions, and aberrant myelination and axonal phenotypes. The loss of normal C1ORF194 protein altered intracellular Ca2+ homeostasis and upregulated Ca2+ handling regulatory proteins. These findings describe a novel protein with vital functions in peripheral nervous systems and broaden the causes of Charcot-Marie-Tooth disease, which open new avenues for the diagnosis and treatment of related neuropathies.

Decreased Plasma Maresin 1 Concentration Is Associated with Diabetic Foot Ulcer.

AIMS: To assess the maresin 1 (MaR1) contents in type 2 diabetic patients with or without diabetic foot ulcer and to analyze the association of MaR1 concentrations with several metabolism-related parameters. METHODS: Plasma MaR1 concentrations were analyzed in 96 subjects with normal glucose tolerant (NC, n = 43), type 2 diabetes (T2DM, n = 40), or diabetic foot ulcer (DFU, n = 13). The intravenous glucose tolerance test (IVGTT) and biochemical parameters were measured in all participants. RESULTS: Plasma MaR1 concentrations were significant decreased in type 2 diabetes patient with or without DFU compared with NC (both P < 0.001) and were lowest in DFU patients among these 3 groups. (DFU vs. T2DM, P < 0.05). Plasma MaR1 concentrations were negatively correlated with BMI, waist circumference (Wc), waist hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), LDL-c, FPG, 2hPG, HbA1c, and homeostasis model assessment for insulin resistance (HOMA-IR) (all P < 0.05) and were positively correlated with HDL-c, acute insulin response (AIR), area under the curve of the first-phase (0-10 min) insulin secretion (AUC), and homeostasis model assessment for beta-cell function (HOMA-ß) (all P < 0.05). After adjusting for age and sex, Wc, WHR, TG, FPG, 2hPG, HbA1c, HOMA-IR, AIR, AUC, and HOMA-ß remain statistically significant (all P < 0.05). CONCLUSIONS: Plasma MaR1 concentration were decreased in T2DM with or without DFUs and were the lowest in DFU patients. The decreased plasma MaR1 strongly associated with obesity, impaired glucose and lipid metabolism, reduced first-phase of glucose-stimulated insulin secretion, and enhanced insulin resistance.

Tetrahydrocurcumin mitigates acute hypobaric hypoxia-induced cerebral oedema and inflammation through the NF-κB/VEGF/MMP-9 pathway.

High-altitude cerebral oedema (HACE) is a potentially fatal manifestation of high-altitude sickness and is caused partly by inflammation and the blood-brain barrier disruption. Tetrahydrocurcumin (THC) has been reported to exert effective antioxidative and anti-inflammatory effects; This study sought to elucidate the underlying mechanism of THC in mitigating HACE using a mouse model. Our results revealed that prophylactic administration of THC (40 mg/kg) for 3 days significantly alleviated the increase in brain water content (BWC), interleukin-1ß (IL-1ß) and TNF-α levels caused by acute hypobaric hypoxia (AHH). Additionally, superoxide dismutase (SOD) activity was increased by THC to enhance the ability to resist hypoxia. Histological and ultrastructural analysis of the cerebrum revealed that THC administration mitigated AHH-induced pericellular oedema and reduced the perivascular space, resulting in the simultaneous remission of oedema and protection of mitochondria in the cerebrum. In vitro, astrocytes exposed to hypoxia (4% O2 ) for 24 hr exhibited and increase in IL-1ß expression followed by an increase in vascular endothelial growth factor (VEGF) levels. Furthermore, THC administration remarkably downregulated VEGF, matrix metallopeptidase-9 (MMP-9), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression, both in vivo and in vitro. Our data highlight the potential prophylactic activity of THC in HACE, it effectively mitigates AHH-induced cerebral oedema and inflammation is associated with the inhibition of the NF-κB/ VEGF/MMP-9 pathways.

Synaptotagmin-11 inhibits cytokine secretion and phagocytosis in microglia.

Cytokine secretion and phagocytosis are key functions of activated microglia. However, the molecular mechanisms underlying their regulation in microglia remain largely unknown. Here, we report that synaptotagmin-11 (Syt11), a non-Ca2+ -binding Syt implicated in Parkinson disease and schizophrenia, inhibits cytokine secretion and phagocytosis in microglia. We found Syt11 expression in microglia in brain slices and primary microglia. Interestingly, Syt11-knockdown (KD) increased cytokine secretion and NO release in primary microglia both in the absence and presence of lipopolysaccharide. NF-κB was activated in untreated KD microglia together with enhanced synthesis of IL-6, TNF-α, IL-1ß, and iNOS. When the release capacity was assessed by the ratio of extracellular to intracellular levels, only the IL-6 and TNF-α secretion capacity was increased in Syt11-KD cells, suggesting that Syt11 specifically regulates conventional secretion. Consistently, Syt11 localized to the trans-Golgi network and recycling endosomes. In addition, Syt11 was recruited to phagosomes and its deficiency enhanced microglial phagocytosis. All the KD phenotypes were rescued by expression of an shRNA-resistant Syt11, while overexpression of Syt11 suppressed cytokine secretion and phagocytosis. Importantly, Syt11 also inhibited microglial phagocytosis of α-synuclein fibrils, supporting its association with Parkinson disease. Taken together, we propose that Syt11 suppresses microglial activation under both physiological and pathological conditions through the inhibition of cytokine secretion and phagocytosis.

EP2-PKA signaling is suppressed by triptolide in lipopolysaccharide-induced microglia activation.

BACKGROUND: Microglia are key players for the inflammatory responses in the central nervous system. Suppression of microglial activation and the resulting production of proinflammatory molecules are considered a promising strategy to alleviate the progression of neurodegenerative disorders. Triptolide was demonstrated as a potent anti-inflammatory compound both in vitro and in vivo. The present study explored potential signal pathways of triptolide in the lipopolysaccharide (LPS)-induced inflammatory response using primary rat microglial cells. FINDINGS: Microglial cells were pretreated with triptolide and stimulated with LPS. To investigate the anti-inflammatory effect of triptolide, we used Griess reagent and Western blot for NO release and iNOS expression, respectively. Moreover, we applied microglia-conditioned medium to neuronal cells and used the MTS assay to test cell viability. We found that triptolide inhibited LPS-induced NO and iNOS synthesis in microglial cells, which in turn protected neurons. To evaluate the involvement of the EP2 pathway, we used real-time PCR and Western blot to determine EP2 expression. We found that LPS induced a large increase in EP2 expression in microglia, and triptolide almost completely inhibited LPS-induced EP2 expression. Using the selective EP2 agonist butaprost and the EP2 antagonist AH6809, we determined that triptolide inhibited LPS-stimulated NO production in microglia mainly through the EP2 pathway. Additionally, by further treating triptolide-treated microglia with the downstream PKA-specific activator 6-Bnz-cAMP or the Epac-specific activator 8-pCPT-2-O-Me-cAMP, we found that 6-Bnz-cAMP but not 8-pCPT-2-O-Me-cAMP increased NO production in triptolide-LPS treated microglia. These results indicate that the EP2-PKA pathway is very important for triptolide's effects. CONCLUSIONS: Triptolide inhibits LPS-stimulated NO production in microglia via a signaling mechanism involving EP2 and PKA. This finding may help establish the pharmacological function of triptolide in neurodegenerative disorders. Moreover, the observation of inflammatory EP2 signaling in primary microglia provides important evidence that EP2 regulates innate immunity in the central nervous system.

Electroacupuncture remediates glial dysfunction and ameliorates neurodegeneration in the astrocytic α-synuclein mutant mouse model.

BACKGROUND: The acupuncture or electroacupuncture (EA) shows the therapeutic effect on various neurodegenerative diseases. This effect was thought to be partially achieved by its ability to alleviate existing neuroinflammation and glial dysfunction. In this study, we systematically investigated the effect of EA on abnormal neurochemical changes and motor symptoms in a mouse neurodegenerative disease model. METHODS: The transgenic mouse which expresses a mutant α-synuclein (α-syn) protein, A53T α-syn, in brain astrocytic cells was used. These mice exhibit extensive neuroinflammatory and motor phenotypes of neurodegenerative disorders. In this study, the effects of EA on these phenotypic changes were examined in these mice. RESULTS: EA improved the movement detected in multiple motor tests in A53T mutant mice. At the cellular level, EA significantly reduced the activation of microglia and prevented the loss of dopaminergic neurons in the midbrain and motor neurons in the spinal cord. At the molecular level, EA suppressed the abnormal elevation of proinflammatory factors (tumor necrosis factor-α and interleukin-1ß) in the striatum and midbrain of A53T mice. In contrast, EA increased striatal and midbrain expression of a transcription factor, nuclear factor E2-related factor 2, and its downstream antioxidants (heme oxygenase-1 and glutamate-cysteine ligase modifier subunits). CONCLUSIONS: These results suggest that EA possesses the ability to ameliorate mutant α-syn-induced motor abnormalities. This ability may be due to that EA enhances both anti-inflammatory and antioxidant activities and suppresses aberrant glial activation in the diseased sites of brains.

Effects of benzo(a)pyrene on differentially expressed genes and haemocyte parameters of the clam Venerupis philippinarum.

In this study a suppression subtractive hybridisation method was employed to identify differentially expressed genes of the clam Venerupis philippinarum exposed to benzo(a)pyrene (BaP). Nineteen known transcripts and seven predicted proteins were found from the subtractive cDNA library of the clam, which could provide more sequence information for further study. Seven of the differentially expressed genes were selected for mRNA expression analysis. Real-time PCR analysis revealed that the expression level of the selected cDNAs of clams was up-regulated to varying degrees by different concentration of BaP. They are suggested as potential molecular biomarkers for polycyclic aromatic hydrocarbons (PAHs) pollution monitoring in aquatic ecosystems. In addition, haemocyte parameters were also measured, and a decrease of total haemocyte counts and suppression of antibacterial and bacteriolytic activities were detected in BaP-stressed clams. We suggest that the modulation of the expression of the selected genes caused by PAHs probably leads to the disturbance of the immune defense of the clam. Meanwhile, the adverse effects of PAHs on haemocyte parameters caused the suppression of the immune defense and susceptibility to infectious diseases. Therefore, it is inferred that PAHs pollutants could interact with components of the immune system and interferes with defense functions of the clam V. philippinarum.

An MRI-Based Radiomics Nomogram for Differentiation of Benign and Malignant Vertebral Compression Fracture.

RATIONALE AND OBJECTIVES: This study aimed to develop and validate a magnetic resonance imaging (MRI)-based radiomics nomogram combining radiomics signatures and clinical factors to differentiate between benign and malignant vertebral compression fractures (VCFs). MATERIALS AND METHODS: A total of 189 patients with benign VCFs (n = 112) or malignant VCFs (n = 77) were divided into training (n = 133) and validation (n = 56) cohorts. Radiomics features were extracted from MRI T1-weighted images and short-TI inversion recovery images to develop the radiomics signature, and the Rad score was constructed using least absolute shrinkage and selection operator regression. Demographic and MRI morphological characteristics were assessed to build a clinical factor model using multivariate logistic regression analysis. A radiomics nomogram was constructed based on the Rad score and independent clinical factors. Finally, the diagnostic performance of the radiomics nomogram, clinical model, and radiomics signature was validated using receiver operating characteristic and decision curve analysis (DCA). RESULTS: Six features were used to build a combined radiomics model (combined-RS). Pedicle or posterior element involvement, paraspinal mass, and fluid sign were identified as the most important morphological factors for building the clinical factor model. The radiomics signature was superior to the clinical model in terms of the area under the curve (AUC), accuracy, and specificity. The radiomics nomogram integrating the combined-RS, pedicle or posterior element involvement, paraspinal mass, and fluid sign achieved favorable predictive efficacy, generating AUCs of 0.92 and 0.90 in the training and validation cohorts, respectively. The DCA indicated good clinical usefulness of the radiomics nomogram. CONCLUSION: The MRI-based radiomics nomogram, combining the radiomics signature and clinical factors, showed favorable predictive efficacy for differentiating benign from malignant VCFs.

Genetic insights into the 'sandwich fusion' subtype of Klippel-Feil syndrome: novel FGFR2 mutations identified by 21 cases of whole-exome sequencing.

BACKGROUND: Klippel-Feil syndrome (KFS) is a rare congenital disorder characterized by the fusion of two or more cervical vertebrae during early prenatal development. This fusion results from a failure of segmentation during the first trimester. Although six genes have previously been associated with KFS, they account for only a small proportion of cases. Among the distinct subtypes of KFS, "sandwich fusion" involving concurrent fusion of C0-1 and C2-3 vertebrae is particularly noteworthy due to its heightened risk for atlantoaxial dislocation. In this study, we aimed to investigate novel candidate mutations in patients with "sandwich fusion." METHODS: We collected and analyzed clinical data from 21 patients diagnosed with "sandwich fusion." Whole-exome sequencing (WES) was performed, followed by rigorous bioinformatics analyses. Our focus was on the six known KFS-related genes (GDF3, GDF6, MEOX1, PAX1, RIPPLY2, and MYO18). Suspicious mutations were subsequently validated through in vitro experiments. RESULTS: Our investigation revealed two novel exonic mutations in the FGFR2 gene, which had not previously been associated with KFS. Notably, the c.1750A > G variant in Exon 13 of FGFR2 was situated within the tyrosine kinase domain of the protein, in close proximity to several established post-translational modification sites. In vitro experiments demonstrated that this certain mutation significantly impacted the function of FGFR2. Furthermore, we identified four heterozygous candidate variants in two genes (PAX1 and MYO18B) in two patients, with three of these variants predicted to have potential clinical significance directly linked to KFS. CONCLUSIONS: This study encompassed the largest cohort of patients with the unique "sandwich fusion" subtype of KFS and employed WES to explore candidate mutations associated with this condition. Our findings unveiled novel variants in PAX1, MYO18B, and FGFR2 as potential risk mutations specific to this subtype of KFS.

Longitudinal Cervical Length Measurements and Spontaneous Preterm Birth in Singleton and Twin Pregnancies.

Importance: Changes in cervical length in twin pregnancies exhibit various patterns, but it is unclear whether the mechanism underlying spontaneous preterm birth (sPTB) is consistent. The existence of detailed phenomena in singleton pregnancies is also unclear. Objectives: To explore the different patterns in cervical length trajectories in singleton and twin pregnancies and to analyze whether the immunological mechanisms of sPTB are consistent among these cervical length patterns. Design, Setting, and Participants: This cohort study recruited pregnant individuals who received antenatal care and delivered at Peking University Third Hospital in Beijing, China, between January 1, 2014, and December 31, 2022. Individuals with singleton and twin pregnancies were included. Exposures: Cervical length measurements and white blood cell (WBC) indicators. Main Outcomes and Measures: The primary outcome was sPTB. Longitudinal trajectory cluster analysis was used to identify patterns of changes in cervical length in singleton and twin pregnancies. A random-effects model with cubic spline was used to fit and compare the longitudinal trajectory of WBC indicators among early preterm birth, moderate to late preterm birth, and term birth. Results: A total of 43 559 pregnant individuals were included; of these, 41 706 had singleton pregnancies (mean [SD)] maternal age, 33.0 [4.0] years) and 1853 had twin pregnancies (mean [SD] maternal age, 33.3 [3.6] years). Two distinct patterns of cervical length changes were observed in both singleton and twin pregnancies: shortened (21 366 singletons and 546 twins) and stable (20 340 singletons and 1307 twins). In singleton pregnancies, WBC count was associated with early sPTB in individuals with both shortened cervix (odds ratio [OR], 1.35; 95% CI, 1.00-1.82) and stable cervix (OR, 1.64; 95% CI, 1.07-2.50). However, for twin pregnancies, the association of WBC count (OR, 3.13; 95% CI, 1.58-6.18) with the risk of early sPTB was observed only in individuals with a shortened cervix. Conclusions and Relevance: This study identified 2 distinct cervical length patterns: shortened and stable. These patterns revealed 2 preterm birth mechanisms in twin pregnancies, with the immunopathogenesis of sPTB found only in the shortened cervix pattern; in singleton pregnancies, maternal immune response was associated with a higher risk of sPTB regardless of a shortened or stable cervix.