Novel fluorescence probe for ClO- in living cells: Based on FRET mechanism.

Hypochlorous acid (HClO) as a kind of reactive oxygen species (ROS) plays a vital role in many biological processes. Organic fluorescence probes have attracted great interests for the detection of HClO, due to their relatively high selectivity and sensitivity, satisfactory spatiotemporal resolution and good biocompatibility. Constructing fluorescence probes to detect HClO with advantages of large Stokes shift, wide emission gap, near infrared emission and good water solubility is still challenging. In this work, a new ratiometric fluorescence probe (named HCY) for HClO was developed. FRET-based HCY was constructed by bonding a coumarin and a flavone fluorophore. In absence of HClO, HCY exists FRET process, however, FRET is inhibited in the presence of HClO because the conjugated double bond broke. Due to the good match of the emission spectrum of the donor and the absorption spectrum of the acceptor, the FRET system appears favorable energy transfer efficiency. HCY showed high sensitivity and rapid response time. The linearity between the ratios of fluorescence intensity and concentration of HClO was established with a low limit of detection. What's more, HCY was also applied for fluorescence images of HClO in RAW264.7 cells.

NLRC5 promotes tumorigenesis by regulating the PI3K/AKT signaling pathway in cervical cancer.

Cervical cancer (CC) is the fourth most common cancer among women worldwide. NLR Family CARD Domain Containing 5 (NLRC5) plays an important role in tumorigenesis. However, its effect and mechanism in CC remains unclear. In this study, we aimed to investigate the function of NLRC5 in CC. NLRC5 was found to be down-regulated in CC tissues compared with normal cervical tissues. However, patients with higher NLRC5 expression had better prognosis, patients with higher age, HPV infection, lymph node metastasis, recurrence and histological grade had worse prognosis. Univariate and multivariate analyses showed NLRC5 to be a potential prognostic indicator for CC. Pearson correlation analysis showed that NLRC5 might exert its function in CC through autophagy related proteins, especially LC3. In vitro experiments demonstrated that NLRC5 inhibited LC3 levels and promoted the proliferation, migration, and invasion of CC cells by activating the PI3K/AKT signaling pathway. Treatment with LY294002 reversed the above phenotype. Taken together, our finding suggested that NLRC5 would participate in cervical tumorigenesis and progression by regulating PI3K/AKT signaling pathway. In addition, NLRC5 and LC3 combined as possible predictors in CC.

A wide-bandgap graphene-like structure C6BN with ultra-low dielectric constant.

This study introduces a new wide-bandgap graphene-like structure, denoted as C6BN, achieved by incorporating an eight-electron BN pair, substantially modifying its electronic properties. Utilizing extensive density functional calculations, we comprehensively analyzed the stability, electronic structure, mechanical properties, and optical-electrical characteristics of C6BN. Our investigations reveal the material's exceptional thermodynamic, mechanical, and dynamic stability. Notably, the calculated wide bandgap of 2.81 eV in C6BN, supported by analyses of energy levels, band structures, and density of states, positions it as a promising two-dimensional wide-bandgap semiconductor. Additionally, C6BN exhibits isotropic mechanical features, highlighting its inherent flexibility. Remarkably, our calculations indicate an ultra-low dielectric constant (k = 1.67) for C6BN, surpassing that of well-established third-generation semiconductors. Further exploration into the thermoelectric properties of C6BN demonstrates its promising performance, as evidenced by calculations of thermal conductivity (κ), power factor (P), and Seebeck coefficient (S). In summary, our findings underscore the significant potential of the proposed C6BN structure as a flexible two-dimensional material poised to drive future advancements in electronic and energy-related technologies.

Comparative dosimetric study of h-IMRT and VMAT plans for breast cancer after breast-conserving surgery.

AIM: To compare the dosimetric advantages and disadvantages between hybrid intensity-modulated radiation therapy (h-IMRT) and the volumetric modulated arc therapy (VMAT) technique in hypofractionated whole-breast irradiation (HF-WBI) for early-stage breast cancer (BC). METHODS: The dose distribution of h-IMRT and VMAT plans was compared in 20 breast cancer patients. This comparison included evaluation of dosimetric parameters using dose volume histograms (DVHs) for the planning target volume (PTV) and organs-at-risk (OARs). Additionally, the study examined the normal tissue complication probability (NTCP), the second cancer complication probability (SCCP) and the tumor control probability (TCP) based on different models. RESULTS: Significant differences were detected between the two plans, in terms of Machine units (MUs), the control points, 95 % volume (V95 %), dose homogeneity index (DHI) and conformity index (CI). The endpoint of grade II radiation pneumonitis and cardiac death due to ischemic heart disease were assessed. In h-IMRT plan, the NTCP values were marginally lower for radiation pneumonitis and slightly higher for cardiac death compared to VMAT plan, as determined by the Lyman-Kutcher-Burman model. The Schneider model was employed to predict the SCCP for both the bilateral lungs and contralateral breast, the results demonstrate that the h-IMRT plan outperforms the VMAT plan, with statistical significance. Additionally, the LQ-Poisson model was employed to forecast the TCP of the PTV, showing that the h-IMRT plan outperformed the VMAT plan (P > 0.05). CONCLUSION: The h-IMRT technique, offering superior dose coverage and better therapeutic efficacy with fewer side effects as calculated by models, is more suitable for HF-WBI compared to the VMAT technique.

STIM1 Mediates Methamphetamine-Induced Neuronal Autophagy and Apoptosis.

Methamphetamine (METH) is a widely abused amphetamine-type psychoactive drug that causes serious health problems. Previous studies have demonstrated that METH can induce neuron autophagy and apoptosis in vivo and in vitro. However, the molecular mechanisms underlying METH-induced neuron autophagy and apoptosis remain poorly understood. Stromal interacting molecule 1 (STIM1) was hypothesized to be involved in METH-induced neuron autophagy and apoptosis. Therefore, the expression of STIM1 protein was measured and the effect of blocking STIM1 expression with siRNA was investigated in cultured neuronal cells, and the hippocampus and striatum of mice exposed to METH. Furthermore, intracellular calcium concentration and endoplasmic reticulum (ER) stress-related proteins were determined in vitro and in vivo in cells treated with METH. The results suggested that STIM1 mediates METH-induced neuron autophagy by activating the p-Akt/p-mTOR pathway. METH exposure also resulted in increased expression of Orai1, which was reversed after STIM1 silencing. Moreover, the disruption of intracellular calcium homeostasis induced ER stress and up-regulated the expression of pro-apoptotic protein CCAAT/enhancer-binding protein homologous protein (CHOP), resulting in classic mitochondria apoptosis. METH exposure can cause neuronal autophagy and apoptosis by increasing the expression of STIM1 protein; thus, STIM1 may be a potential gene target for therapeutics in METH-caused neurotoxicity.

Hepatic infarction occurred after 125I particle stent treatment for hepatocellular carcinoma with portal vein tumor thrombus: A case report.

BACKGROUND: Hepatic infarction is a rare liver condition. The purpose of this study is to report a case of hepatic infarction caused by thrombus formation following portal vein stent implantation in a patient with hepatocellular carcinoma and portal vein tumor thrombus, and to explore the underlying causes. CASE REPORT: The patient in this study was a 52-year-old male admitted with diffuse hepatocellular carcinoma involving the right lobe and portal vein tumor thrombus. After undergoing portal vein stent implantation and 125I particle strand implantation treatment, the portal vein was patent, and the pressure decreased. However, multiple instances of hepatic artery chemoembolization combined with targeted immunotherapy resulted in gradual reduction in the diameter of the hepatic artery and affecting hepatic arterial blood flow. Two months post-stent implantation, thrombus formation within the stent was noted, and the patient's condition did not improve with anticoagulant therapy, as evidenced by follow-up CT scans showing an increase in thrombi. Six months later, the patient suffered from gastrointestinal bleeding and, despite emergency esophagogastric variceal ligation and hemostatic treatment, developed hepatic parenchymal infarction and liver function failure. CONCLUSIONS: We reveal the underlying cause is that (1) thrombus formation within the portal vein stent, leading to portal vein embolism and obstructed blood flow due to exacerbate portal hypertension after various treatments; and (2) the effect of hepatic artery chemoembolization, immunotherapy, and targeted therapy on tumor angiogenesis, causing reduced hepatic artery diameter and impaired arterial blood flow. These factors disrupt the liver's dual blood supply system, ultimately contributing to hepatic infarction. To our knowledge, this is the first report of hepatic infarction as a complication following portal vein stent implantation for hepatocellular carcinoma with portal vein tumor thrombus, and it holds significant reference value for guiding the treatment of hepatocellular carcinoma with concurrent portal vein tumor thrombus in a clinical setting.

Bizarre parosteal osteochondromatous proliferation (Nora lesion) involving the spine: a case report and systematic review.

Bizarre parosteal osteochondromatous proliferation (BPOP), also termed Nora lesion, is a rare, benign tumor most often located in the hands and feet. We herein present the second reported case of BPOP affecting the spine, an uncommon location. One year after surgical excision, the patient was pain-free and showed no evidence of recurrence. We reviewed a total of 323 cases of BPOP among 101 articles, providing the first systematic update on the latest knowledge of BPOP. The age of patients with BPOP ranges from 3 months to 87 years, peaking in the second and third decades of life. The hands are the most common location of BPOP (58.39%), followed by the feet (20.81%). Imaging features play a key role in the diagnosis of BPOP, but histopathologic diagnosis remains the gold standard. Differential diagnosis of BPOP should be based on the epidemiologic and clinical features as well as clinical examination findings. Surgical resection is the most extensively used treatment for BPOP. Recurrence is common (37.44%) and can be treated with re-excision. This article can deepen our understanding of BPOP and will be helpful for the diagnosis and treatment of BPOP in clinical practice.

Blocking Sigmar1 exacerbates methamphetamine-induced hypertension.

AIM: Methamphetamine (METH) chronic exposure is an important risk factor for hypertension development. However, the mechanisms behind METH-induced hypertension remain unclear. Therefore, we aimed to reveal the potential mechanisms underlying METH-induced hypertension. METHODS AND RESULTS: We structured the mouse hypertension model by METH, and observed that METH-treated mice have presented vascular remodeling (large-and small-size arteries) with collagen deposit around the vessel and increasing blood pressure (BP) and Sigma1 receptor (Sigmar1) in vascular tissue. We hypothesized that Sigmar1 is crucial in METH-induced hypertension and vascular remodeling. Sigmar1 knockout (KO) mice and antagonist (BD1047) pretreated mice exposed to METH for six-week showed higher BP and more collagen deposited around vessels than wild-type (WT) mice exposed to METH for six-week, in contrast, mice pretreated with Sigmar1 agonist (PRE-084) had unchanged BP and perivascular collagen despite the six-week METH exposure. Furthermore, we found that METH exposure induced vascular smooth muscle cells (VSMCs) and mesenchymal stem cells to differentiate into the myofibroblast-like cell and secrete collagen into surrounding vessels. Mechanically, Sigmar1 can suppress the COL1A1 expression by blocking the classical fibrotic TGF-ß/Smad2/3 signaling pathway in METH-exposed VSMCs and mesenchymal stem cells. CONCLUSION: Our results suggest that Sigmar1 is involved in METH-induced hypertension and vascular fibrosis by blocking the activation of the TGF-ß/Smad2/3 signaling pathway. Accordingly, Sigmar1 may be a novel therapeutic target for METH-induced hypertension and vascular fibrosis.

Prevalence of anxiety, depression, sleeping problems, cognitive impairment, and suicidal ideation in people with autoimmune skin diseases.

BACKGROUND: Autoimmune skin diseases (ASDs) such as psoriasis and vitiligo, in addition to causing visible skin symptoms, are closely associated with psychological health issues. However, a comprehensive understanding of the prevalence of these psychological comorbidities in affected individuals is lacking. This study aims to identify the prevalence of anxiety, depression, sleeping problems, cognitive impairment, and suicidal ideation in people with ASDs. METHOD: PubMed, MEDLINE, Web of Science, and Cochrane Library searches were conducted from 1993 to May 2024. Observational studies reporting prevalence data for anxiety, depression, sleeping problems, cognitive impairment, and suicidal ideation among people with ASDs were included in the analysis. The Newcastle-Ottawa scale was used to evaluate the quality of studies. RESULTS: The study included 114 studies from 37 countries including 823,975 participants. The estimated pooled prevalence of anxiety in patients with ASDs was 33.3% (95% CI: 27.3-29.3%). The estimated pooled prevalence of depression was 33.7% (95% CI: 29.2-38.1%). The estimated pooled prevalence of sleeping problems was 45.0% (95% CI:31.6-58.4%). The estimated pooled prevalence of cognitive impairment and suicidal ideation was 30.8% (95% CI:15.0-46.7%) and 21.6% (95% CI:13.4-29.8%), respectively. The most common mental disorder in patients with systemic lupus erythematosus and psoriasis was sleeping problems at 55.9% (95% CI: 35.6-76.1%, I2 = 97%) and 39.0% (95% CI: 21.1-56.9%, I2 = 99%). CONCLUSION: Among patients with ASDs, anxiety, depression, sleeping problems, cognitive impairment, and suicidal ideation were common. The most prevalent mental disorder among patients with systemic lupus erythematosus and psoriasis was sleeping problems. Those with ASDs may experience considerable psychological burdens, and integrated mental health support is necessary for their treatment.

NLRC5 promotes endometrial carcinoma progression by regulating NF-κB pathway-mediated mismatch repair gene deficiency.

The innate immune molecule NLR family CARD domain-containing 5 (NLRC5) plays a significant role in endometrial carcinoma (EC) immunosurveillance. However, NLRC5 also plays a protumor role in EC cells. Mismatch repair gene deficiency (dMMR) can enable tumors to grow faster and also can exhibit high sensitivity to immune checkpoint inhibitors. In this study, we attempted to determine whether NLRC5-mediated protumor role in EC is via the regulation of dMMR. Our findings revealed that NLRC5 promoted the proliferation, migration, and invasion abilities of EC cells and induced the dMMR status of EC in vivo and in vitro. Furthermore, the mechanism underlying NLRC5 regulated dMMR was also verified. We first found NLRC5 could suppress nuclear factor-kappaB (NF-κB) pathway in EC cells. Then we validated that the positive effect of NLRC5 in dMMR was restricted when NF-κB was activated by lipopolysaccharides in NLRC5-overexpression EC cell lines. In conclusion, our present study confirmed the novel NLRC5/NF-κB/MMR regulatory mechanism of the protumor effect of NLRC5 on EC cells, thereby suggesting that the NLRC5-mediated protumor in EC was depend on the function of MMR.

Expression pattern of serum interleukin-7 in elderly septic patients and its prognostic value for predicting short-term mortality.

BACKGROUND: The identification of novel prognostic biomarkers in elderly septic patients are essential for the improvement of mortality in sepsis in the context of precision medicine. The purpose of this study was to explore the expression pattern and prognostic value of serum interleukin-7 (IL-7) in predicting 28-day mortality in elderly patients with sepsis. METHODS: Patients were retrospectively enrolled according to the sepsis-3.0 diagnostic criteria and divided into the survival group and non-survival group based on the clinical outcome at the 28-day interval. The baseline characteristic data, samples for the laboratory tests, and the SOFA, Acute Physiology and Chronic Health Evaluation (APACHE II), as well as Glasgow coma scale (GCS) scores, were recorded within 24 h after admission to the emergency department. Serum levels of IL-7 and TNF-α of the patients were quantified by the Luminex assay. Spearman correlation analysis, logistic regressive analysis and receiver operating characteristic curve (ROC) analysis were performed, respectively. RESULTS: Totally, 220 elderly patients with sepsis were enrolled, 151 of whom died in a 28-day period. Albumin (ALB), high-density lipoprotein (HDL), systolic pressure (SBP), and platelet (PLT) were found to be significantly higher in the survival group (p < 0.05). IL-7 was shown to be correlated with TNF-α in the non-survival group (p = 0.030) but not in the survival group (p = 0.194). No correlation was shown between IL-7 and other factors (p > 0.05). IL-7 and TNF-α were found to be independent risk factors associated with the 28-day mortality (OR = 1.215, 1.420). Combination of IL-7, SOFA and ALB can make an AUROC of 0.874 with the specificity of 90.77 %. Combination of IL-7 and TNF-α can make an AUROC of 0.901 with the sensitivity of 90.41 % while the combination of IL-7, TNF-α, and ALB can make an AUROC of 0.898 with the sensitivity of 94.52 %. CONCLUSIONS: This study highlights the importance of monitoring the serum level of IL-7 and TNF-α in elderly septic patients as well as evaluating the combinations with other routine risk factors which can be potentially used for the identification of elderly septic patients with higher risk of mortality.

[Research on differential quality markers of medicine herbs for Danggui Buxue Decoction before and after processing based on fingerprint and network pharmacology].

The different quality markers of Danggui Buxue Decoction before and after processing were studied based on fingerprint and network pharmacological research, and the seven screened index components were quantitatively analyzed, so as to provide an experimental basis for the quality evaluation of Danggui Buxue Decoction before and after processing. HPLC method was used to establish fingerprints of Danggui Buxue Decoction before and after processing, and a multivariate statistical method was used to analyze the cha-racteristic maps and common peak areas of Danggui Buxue Decoction before and after processing. The different characteristic components before and after processing were screened out, and related targets and pathways of their different components were constructed based on network pharmacology. Their components were quantitatively analyzed. A total of 13 common peaks were identified in the fingerprint of the Danggui Buxue Decoction sample, and seven main chemical components were identified, with similarity > 0.911. Further cluster analysis, principal component analysis, and partial least squares discriminant analysis were used to distinguish raw and processed products. According to VIP value, the main difference components 1, 2, 6, 13, and 5 of Danggui Buxue Decoction before and after processing were screened. By combining the "five principles" of TCM Q-marker and network pharmacology, 5-hydroxymethylfurfural, ferulic acid, calycosin-7-O-ß-D-glucoside, calycosin, ligusticolide, formononetin, and ligusticolide I were selected as the signature components of quality difference before and after processing. The results of the quantitative analysis showed that the content of ligustrin I, calycosin, formononetin, and ligusticum decreased after the Danggui Buxue Decoction was processed. The content of calycosin-7-O-ß-D-glucoside and ferulic acid increased. At the same time, a new chemical compound, namely 5-hydroxymethylfurfural was produced. The established fingerprint analysis method is stable and reliable. Combined with network pharmacology and quantitative research, it screens out the differential Q-marker, which provides an experimental basis for further research on processed products of Danggui Buxue Decoction.

Ultra-flat bands at large twist angles in group-V twisted bilayer materials.

Flat bands in 2D twisted materials are key to the realization of correlation-related exotic phenomena. However, a flat band often was achieved in the large system with a very small twist angle, which enormously increases the computational and experimental complexity. In this work, we proposed group-V twisted bilayer materials, including P, As, and Sb in the ß phase with large twist angles. The band structure of twisted bilayer materials up to 2524 atoms has been investigated by a deep learning method DeepH, which significantly reduces the computational time. Our results show that the bandgap and the flat bandwidth of twisted bilayer ß-P, ß-As, and ß-Sb reduce gradually with the decreasing of twist angle, and the ultra-flat band with bandwidth approaching 0 eV is achieved. Interestingly, we found that a twist angle of 9.43° is sufficient to achieve the band flatness for ß-As comparable to that of twist bilayer graphene at the magic angle of 1.08°. Moreover, we also find that the bandgap reduces with decreasing interlayer distance while the flat band is still preserved, which suggests interlayer distance as an effective routine to tune the bandgap of flat band systems. Our research provides a feasible platform for exploring physical phenomena related to flat bands in twisted layered 2D materials.

[Preparation technology comparison and performance evaluation of different protein A affinity chromatographic materials].

Protein A affinity chromatographic materials are widely used in clinical medicine and biomedicine because of their specific interactions with immunoglobulin G (IgG). Both the characteristics of the matrix, such as its structure and morphology, and the surface modification method contribute to the affinity properties of the packing materials. The specific, orderly, and oriented immobilization of protein A can reduce its steric hindrance with the matrix and preserve its bioactive sites. In this study, four types of affinity chromatographic materials were obtained using agarose and polyglycidyl methacrylate (PGMA) spheres as substrates, and multifunctional epoxy and maleimide groups were used to fix protein A. The effects of the ethylenediamine concentration, reaction pH, buffer concentration, and other conditions on the coupling efficiency of protein A and adsorption performance of IgG were evaluated. Multifunctional epoxy materials were prepared by converting part of the epoxy groups of the agarose and PGMA matrices into amino groups using 0.2 and 1.6 mol/L ethylenediamine, respectively. Protein A was coupled to the multifunctional epoxy materials using 5 mmol/L borate buffer (pH 8) as the reaction solution. When protein A was immobilized on the substrates by maleimide groups, the agarose and PGMA substrates were activated with 25% (v/v) ethylenediamine for 16 h to convert all epoxy groups into amino groups. The maleimide materials were then converted into amino-modified materials by adding 3 mg/mL 3-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS) dissolved in dimethyl sulfoxide (DMSO) and then suspended in 5 mmol/L borate buffer (pH 8). The maleimide groups reacted specifically with the C-terminal of the sulfhydryl group of recombinant protein A to achieve highly selective fixation on both the agarose and PGMA substrates. The adsorption performance of the affinity materials for IgG was improved by optimizing the bonding conditions of protein A, such as the matrix type, matrix particle size, and protein A content, and the adsorption properties of each affinity material for IgG were determined. The column pressure of the protein A affinity materials prepared using agarose or PGMA as the matrix via the maleimide method was subsequently evaluated at different flow rates. The affinity materials prepared with PGMA as the matrix exhibited superior mechanical strength compared with the materials prepared with agarose. Moreover, an excellent linear relationship between the flow rate and column pressure of 80 mL/min was observed for this affinity material. Subsequently, the effect of the particle size of the PGMA matrix on the binding capacity of IgG was investigated. Under the same protein A content, the dynamic binding capacity of the affinity materials on the PGMA matrix was higher when the particle size was 44-88 µm than when other particle sizes were used. The properties of the affinity materials prepared using the multifunctional epoxy and maleimide-modified materials were compared by synthesizing affinity materials with different protein A coupling amounts of 1, 2, 4, 6, 8, and 10 mg/mL. The dynamic and static binding capacities of each material for bovine IgG were then determined. The prepared affinity material was packed into a chromatographic column to purify IgG from bovine colostrum. Although all materials showed specific adsorption selectivity for IgG, the affinity material prepared by immobilizing protein A on the PGMA matrix with maleimide showed significantly better performance and achieved a higher dynamic binding capacity at a lower protein grafting amount. When the protein grafting amount was 15.71 mg/mL, the dynamic binding capacity of bovine IgG was 32.23 mg/mL, and the dynamic binding capacity of human IgG reached 54.41 mg/mL. After 160 cycles of alkali treatment, the dynamic binding capacity of the material reached 94.6% of the initial value, indicating its good stability. The developed method is appropriate for the production of protein A affinity chromatographic materials and shows great potential in the fields of protein immobilization and immunoadsorption material synthesis.

Advances in Nano-Functional Materials in Targeted Thrombolytic Drug Delivery.

Thrombotic disease has been listed as the third most fatal vascular disease in the world. After decades of development, clinical thrombolytic drugs still cannot avoid the occurrence of adverse reactions such as bleeding. A number of studies have shown that the application of various nano-functional materials in thrombus-targeted drug delivery, combined with external stimuli, such as magnetic, near-infrared light, ultrasound, etc., enrich the drugs in the thrombus site and use the properties of nano-functional materials for collaborative thrombolysis, which can effectively reduce adverse reactions such as bleeding and improve thrombolysis efficiency. In this paper, the research progress of organic nanomaterials, inorganic nanomaterials, and biomimetic nanomaterials for drug delivery is briefly reviewed.

Unusual optical phenomena inside and near a rotating sphere: the photonic hook and resonance.

Based on the optical Magnus effect, the analytical expressions of the electromagnetic field that a spinning dielectric sphere illuminated by polarized plane waves are derived according to the "instantaneous rest-frame" hypothesis and Minkowski's theory. More attention is paid to the near field. The unusual optical phenomena in mesoscale spheres without material and illumination wave asymmetry that are the photonic hook (PH) and whispering gallery mode (WGM)-like resonance caused by rotation are explored. The impact of resonance scattering on PHs is further analyzed under this framework. The influence of non-reciprocal rotating dimensionless parameter γ on PH and resonance is emphasized. The results in this paper have extensive application prospects in mesotronics, particle manipulation, resonator design, mechatronics, and planetary exploration.

The potential up-regulation risk of 3' UTR SNP (rs10787760 G > A) for the VAX1 gene is associated with NSCLP in the northwest Chinese population.

AIMS: To investigate the association between single nucleotide polymorphisms (SNPs) in 3'UTR region of VAX1, SYT14 and PAX7 genes and the risk of non-syndromic cleft palate (NSCLP) in a northwest Chinese population. MAIN METHODS: A case-control study was conducted in 406 normal controls and 399 NSCLP patients. Using iMLDRTM genotyping technology, eight SNPs of three genes ((rs10787760, rs7086344 at VAX1), (rs1010113, rs851114, and rs485874 at PAX7), and (rs61820397, rs4609425, rs12133399 at SYT14)) were genotyped to investigate the differences in alleles and genotype distribution frequencies between NSCLP patients and healthy controls. RNA Folding Form software was used to predict RNA secondary structure and expression vectors were constructed to explore the function of the relevant SNP. The effect of SNP polymorphism of gene transcription and translation was assessed using qPCR and Western blot analysis. KEY FINDINGS: Among the eight SNPs of three genes, rs10787760 of VAX1 gene was found to be associated with an increased risk of NSCLP (OR = 1.341, CI = 1.004-1.790) and the GA genotype of rs10787760 increased the risk of cleft lip and/or palate (CL/P) about 1.42 times (p < 0.05), and carrying the A allele might increase the risk of NSCL/P in male (OR = 1.356, 95 % CI = 1.010-1.823). But there was no association observed with cleft palate only (CPO). Cell function experiments revealed that the G to A mutation in rs10787760 up-regulated GFP-VAX1 transcriptional level by 2.39 and 3.13 times in two cell lines respectively, and enhance the protein expression of the VAX1 gene further. RNA secondary structure study showed that the rs10787760 (G > A) had two different secondary structures in 3'UTR region. SIGNIFICANCE: The rs10787760 variant in the 3'UTR region of VAX1 gene is associated with CL/P in northwest Chinese population. We hypothesize that the machanism of it might be caused by the RNA differenct fold in the 3'UTR region caused by the polymorphism of the gene. LEVEL OF EVIDENCE: Original Reports.

Evaluation of serum CA125, HE4 and CA724 and the risk of ovarian malignancy algorithm score in the diagnosis of high-grade serous ovarian cancer.

AIM: To develop a new algorithm for the detection of high-grade serous ovarian cancer (HGSOC). METHODS: Patients diagnosed with HGSOC, borderline ovarian tumours (BOTs) or benign ovarian masses (BOMs) were enrolled between February 2019 and December 2020. Patients with BOTs or BOMs were grouped as non-HGSOC. The cases were divided randomly into a training cohort (two-thirds of cases) and a validation cohort (one-third of cases). Logistic regression was used to find risk factors for HGSOC and to create a new algorithm in the training cohort. Receiver operating characteristic curves were used to compare the diagnostic value of tumour biomarkers. Sensitivity and specificity of tumour markers and the new algorithm were calculated in the training cohort and validation cohort. RESULTS: This study found significant differences in age; BRCA1/2 mutation status; CA125, CA724 and HE4 levels; and Risk of Ovarian Malignancy Algorithm score between the two groups.Logistic regression analysis showed that CA125 and BRCA1/2 were risk factors for HGSOC. A new algorithm combining CA125 and BRCA1/2 increased the specificity of CA125 for diagnosis of HGSOC. The new algorithm had sensitivity of 81.08% and specificity of 93.10% in the training cohort. CONCLUSION: The new algorithm using CA125 and BRCA1/2 helped to distinguish between patients with HGSOC and patients with non-HGSOC.

[Effects of Application of Different Organic Materials on Phosphorus Accumulation and Transformation in Vegetable Fields].

Presently, the improvement of soil organic matter is the basis to ensure food security, but the accumulation and transformation characteristics of soil phosphorus (P) as affected by organic matter remain unclear. The accumulation, transformation, and migration characteristics of soil P in different soil layers of vegetable fields were researched under the application of organic materials. Six treatments were set up in the experiment:control (no fertilization), traditional fertilizer application by farmers, biochar, chicken manure, food waste, and straw application. Available phosphorus (Olsen-P), water-soluble phosphorus (CaCl2-P) content, soil phosphorus forms, soil organic matter (SOM), and pH were determined during the pepper harvest period. In the 0-5 cm and 5-10 cm soil layers, the available phosphorus content of traditional fertilization of farmers was higher, and the available phosphorus content of the four organic materials was in the order of straw > biochar > chicken manure > food waste. Compared to that with food waste, the straw and biochar treatments increased soil available phosphorus by 59.6%-67.3% and 29.1%-36.9%, respectively. The straw treatment could easily enhance the soil labile P pool, and soil labile P in the 0-5 cm soil layer increased by 47.3% and 35.1% compared with that under the chicken manure and food waste treatments, respectively. With the increase in soil depth, the proportion of available phosphorus in the chicken manure treatment decreased the least, and available phosphorus of the 20-30 cm soil layer accounted for 55.9% of the topsoil layer but only accounted for 16.0%-34.0% under treatment with the other three materials. Compared with that under the traditional fertilization of farmers, the pH significantly increased by 0.18-0.36 units after the application of organic fertilizer, and the pH of the chicken manure and food waste treatments was significantly higher than that of biochar and straw (P < 0.05). SOM content under the biochar treatment significantly increased by 7.7%-17.6% compared to that under the other three organic materials. Among the four organic materials, the straw treatment boosted the labile P pool the most, which was conducive to the rapid increase in plant-available P. Phosphorus was most likely to migrate downward under the chicken manure treatment. In the field management based on soil fertility enhancement, the application of biochar could not only improve soil pH and SOM but also avoid excessive accumulation of phosphorus in the surface layer, which decreases environmental risks.