Clinical value of ultrasonic indicators in predicting the outcome of caesarean scar pregnancy after pregnancy termination.

BACKGROUND: To investigate the predictive value of ultrasound indicators in early pregnancy for the outcome of caesarean scar pregnancy (CSP) after pregnancy termination. METHODS: This study retrospectively analysed the ultrasound images of 98 CSP patients who underwent transabdominal ultrasound-guided hysteroscopic curettage during early pregnancy at Changsha Hospital for Maternal and Child Health Care between January 2017 and October 2021. Patients were equally divided into a case group and a control group. The case group included 49 CSP patients with postoperative complications, such as intraoperative blood loss ≥ 200 ml or retained products of conception (RPOC). The remaining 49 CSP patients, with similar age and gestational age and with good postoperative outcomes, such as intraoperative blood loss ≤ 50 ml and no RPOC, were included in the control group. CSP was classified into three types according to the location of the gestational sac (GS) relative to the uterine cavity line (UCL) and serosal contour. Differences in ultrasound indicators between the case and control group were compared. RESULTS: There were significant differences between the case and control groups in the mean gestational sac diameter (MGSD), residual myometrium thickness (RMT) between the GS and the bladder, blood flow around the GS at the site of the previous caesarean incision, and types of CSP (P < 0.05). The rs of each ultrasound indicator were as follows: 0.258, -0.485, 0.369, 0.350. The optimal threshold for predicting good postoperative outcomes, such as intraoperative blood loss ≤ 50 ml and no RPOC, by receiver operating characteristic (ROC) curve analysis of the RMT was 2.3 mm. CONCLUSION: Our findings show that the RMT, blood flow around the GS at the site of the previous caesarean incision, and types of CSP have a low correlation with postoperative complications, such as intraoperative blood loss ≥ 200 ml or RPOC, of early pregnancy termination in patients with CSP. To some extent, this study may be helpful for clinical prognostic prediction of patients with CSP and formulation of treatment strategies. Given the low correlation between these three indicators and postoperative complications, further studies are needed to identify indicators that can better reflect the postoperative outcomes of CSP patients.

Radiomics-based ultrasound models for thyroid nodule differentiation in Hashimoto's thyroiditis.

Background: Previous models for differentiating benign and malignant thyroid nodules(TN) have predominantly focused on the characteristics of the nodules themselves, without considering the specific features of the thyroid gland(TG) in patients with Hashimoto's thyroiditis(HT). In this study, we analyzed the clinical and ultrasound radiomics(USR) features of TN in patients with HT and constructed a model for differentiating benign and malignant nodules specifically in this population. Methods: We retrospectively collected clinical and ultrasound data from 227 patients with TN and concomitant HT(161 for training, 66 for testing). Two experienced sonographers delineated the TG and TN regions, and USR features were extracted using Python. Lasso regression and logistic analysis were employed to select relevant USR features and clinical data to construct the model for differentiating benign and malignant TN. The performance of the model was evaluated using area under the curve(AUC), calibration curves, and decision curve analysis(DCA). Results: A total of 1,162 USR features were extracted from TN and the TG in the 227 patients with HT. Lasso regression identified 14 features, which were used to construct the TN score, TG score, and TN+TG score. Univariate analysis identified six clinical predictors: TI-RADS, echoic type, aspect ratio, boundary, calcification, and thyroid function. Multivariable analysis revealed that incorporating USR scores improved the performance of the model for differentiating benign and malignant TN in patients with HT. Specifically, the TN+TG score resulted in the highest increase in AUC(from 0.83 to 0.94) in the clinical prediction model. Calibration curves and DCA demonstrated higher accuracy and net benefit for the TN+TG+clinical model. Conclusion: USR features of both the TG and TN can be utilized for differentiating benign and malignant TN in patients with HT. These findings highlight the importance of considering the entire TG in the evaluation of TN in HT patients, providing valuable insights for clinical decision-making in this population.

Dynamics of Bacterial Diversity and Functions with Physicochemical Properties in Different Phases of Pig Manure Composting.

Bacteria are key drivers in regulating ecosystem functions, and understanding the diversity and dynamic changes in bacteria in composting is very important for optimizing compost. This study investigated the structure, composition, and function of bacterial communities in alkaline pig manure compost using Miseq sequencing, PICRUSt2. The ACE and Chao1 indices of the bacterial communities in various phases were significantly different. Bacterial communities of alkaline pig compost were different from neutral and acidic swine manure compost, and there were 438 genera of common bacteria in various stages. The main bacterium was the phylum Firmicutes. There were six genera, including Romboutsia, Clostridium, Terrisporobacter, norank_f_Marinococcaceae, Saccharomonospora, and unclassified_f_Bacillaceae, that were significantly correlated (p < 0.05), or even extremely significantly correlated (p < 0.001), with the physicochemical properties. TOC, moisture, C/N, and Tem were the key factors that caused changes in bacterial communities in composting. PICRUSt2 analysis showed that there were seven functional groups: metabolism (45.02-48.07%), environmental information processing (15.25-16.00%), genetic information processing (16.97-20.02%), cellular processes (3.63-4.37%), human diseases (0.71-0.82%), organismal systems (0.66-0.77%), and unclassified (13.93-14.36%). This study will provide a reference for improving bacteria growth and reproduction conditions in pig manure composting, optimizing the process, and improving the efficiency of composting.

Pratylenchus zeae a causative agent of Corn Root Rot in Jiangsu Province of China.

Corn (Zea mays L.) plays an important role in China's cash crops, not only as food, but a vital raw material for animal husbandry and industry (Li et al. 2022). Pratylenchus zeae is one of the most damaging root-lesion nematodes (RLN) that can result in decreased yield and quality of crops (Liu et al. 2017). In September 2020, five root/soil samples were collected from the rhizosphere of corn (cv. Zhengdan 958), which had weak growth and root brown lesions in Chenzhou Village, Taolin Town, Donghai County, Lianyungang City, Jiangsu Province of China. Nematodes were extracted from the collected samples using the modified Baermann funnel method (Hooper et al. 2005). RLN were found in all samples, an average of 46 RLN per gram of root and 138 RLN per 100 cm3 of soil. The obtained RLN females were sterilized with 0.3% streptomycin sulfate and then inoculated on each carrot disks individually to obtain the purified population. RLN were examined by morphological and molecular characteristics to confirm the species indentification. The main morphological measurements of adult (n = 15) included body length = 524.7 µm (mean) ± 15.1 (standard deviation) (range = 490.7 to 543.6 µm), stylet = 15.2 µm ± 0.8 (14.2 to 16.8 µm), tail length = 30.3 µm ± 2.5 (26.3 to 35.3 µm), a = 25.6 ± 1.3 (24.4 to 29.3), b = 5.3 ± 0.3 (4.7 to 5.8), c = 17.4 ± 1.4 (14.9 to 19.3), two annules on the lip region. No males were found in the specimens. The morphological characters of this population are consistent with the description of P. zeae (Castillo and Vovlas, 2007). Furthermore, DNA was extracted from individual nematodes. The primers of TW81/AB28 and D2A/D3B (Subbotin et al. 2006) were used to amplified the rDNA-ITS region and rDNA 28S D2-D3 region, respectively. The purified PCR products were ligated into One step ZTOPO-Blunt/TA vector and transformed to Escherichia coli strain DH5α, and then sequenced by Sunya Biotechnology Co., Ltd (Henan, China). The obtained seqences were submitted to NCBI. The rDNA-ITS sequences (669 bp, GenBank Accession No: OP456372 and OP466367) exhibited 95.0% to 97.1% of identity with P. zeae sequences (KU198980 and KU198975). The obtained D2-D3 region of the 28S rDNA sequences (782 bp, OP441397 and OP448675) exhibited 99.7% to 100% identity with P. zeae sequences (EU130893 and KY424269). Consequently, both morphological and molecular data confirmed the identity of P. zeae. To further confirm reproduction on corn, single corn seeds (cv. Zhengdan 958) were sown in eight 2-liter pots filled with 1.8-liter of sterilized soil in greenhouse at 28°C. About 15 days after sowing, each pot with one corn plant with the same growth status was selected to inoculate with 1,000 mixed stage nematodes of P. zeae , Eight pots of uninoculated corn plants were used as controls. After 60 days, the inoculated plants were harvested and brown lesions were observed on roots. No symptoms and nematodes was detected in the control. An average number of RLN per pot was 3,752 in soil and 1,183 in roots were extracted, the reproduction factor (final population/initial population) was 4.94, indicating that P. zeae infects and reproduces well on this corn cultivar. P. zeae has only been reported on corn in Guangxi Province, southern in China(Fang et al. 1994). To our knowledge, this is the fist report of P. zeae infecting corn in Jiangsu Province, eastern in China. As P. zeae can cause great damage to corn, necessary measures should be taken to prevent the spread of P. zeae to other areas.

Theaflavin-3,3'-digallate ameliorates learning and memory impairments in mice with premature brain aging induced by D-galactose.

Age-related neurodegenerative diseases accompanied by learning and memory deficits are growing in prevalence due to population aging. Cellular oxidative stress is a common pathomechanism in multiple age-related disorders, and various antioxidants have demonstrated therapeutic efficacy in patients or animal models. Many plants and plant extracts possess potent antioxidant activity, but the compounds responsible are frequently unknown. Identification and evaluation of these phytochemicals is necessary for optimal targeted therapy. A recent study identified theaflavin-3,3'-digallate (TFDG) as the most potent among a large series of phytochemical antioxidants. Here we examined if TFDG can mitigate learning and memory impairments in the D-galactose model of age-related neurodegeneration. Experimental mice were injected subcutaneously with D-galactose (120 mg/kg) for 56 days. In treatment groups, different doses of TFDG were administered daily by gavage starting on day 29 of D-galactose injection. Model mice exhibited poor learning and memory in the novel object recognition and Y-maze tests, reduced brain/body mass ratio, increased brain glutamate concentration and acetylcholinesterase activity, decreased brain acetylcholine concentration, and lower choline acetyltransferase, glutaminase, and glutamine synthetase activities. Activities of antioxidant enzymes glutathione peroxidase and superoxide dismutase were also reduced, while the concentration of malondialdehyde, a lipid peroxidation product, was elevated. Further, antioxidant genes Nrf2, Prx2, Gsh-px1, and Sod1 were downregulated in brain. Each one of these changes was dose-dependently reversed by TFDG. TFDG is an effective antioxidant response inducer and neuroprotectant that can restore normal neurotransmitter metabolism and ameliorate learning and memory dysfunction in the D-galactose model of age-related cognitive decline.

Is the diagnostic model based on convolutional neural network superior to pediatric radiologists in the ultrasonic diagnosis of biliary atresia?

Background: Many screening and diagnostic methods are currently available for biliary atresia (BA), but the early and accurate diagnosis of BA remains a challenge with existing methods. This study aimed to use deep learning algorithms to intelligently analyze the ultrasound image data, build a BA ultrasound intelligent diagnostic model based on the convolutional neural network, and realize an intelligent diagnosis of BA. Methods: A total of 4,887 gallbladder ultrasound images of infants with BA, non-BA hyperbilirubinemia, and healthy infants were collected. Two mask region convolutional neural network (Mask R-CNN) models based on different backbone feature extraction networks were constructed. The diagnostic performance between the two models was compared through good-quality images at the image level and the patient level. The diagnostic performance between the two models was compared through poor-quality images. The diagnostic performance of BA between the model and four pediatric radiologists was compared at the image level and the patient level. Results: The classification performance of BA in model 2 was slightly higher than that in model 1 in the test set, both at the image level and at the patient level, with a significant difference of p = 0.0365 and p = 0.0459, respectively. The classification accuracy of model 2 was slightly higher than that of model 1 in poor-quality images (88.3% vs. 86.4%), and the difference was not statistically significant (p = 0.560). The diagnostic performance of model 2 was similar to that of the two radiology experts at the image level, and the differences were not statistically significant. The diagnostic performance of model 2 in the test set was higher than that of the two radiology experts at the patient level (all p < 0.05). Conclusion: The performance of model 2 based on Mask R-CNN in the diagnosis of BA reached or even exceeded the level of pediatric radiology experts.

Low threshold optical bistability based on topological edge state in photonic crystal heterostructure with Dirac semimetal.

The special band structure of three-dimensional Dirac semimetal (3D DSM) makes it show strong nonlinear optical characteristics in the terahertz region, which provides a new way to develop terahertz nonlinear devices with low threshold. In this paper, we theoretically study the optical bistability (OB) of transmitted light in a multilayer structure with 3D DSM embedded in two one-dimensional photonic crystals (1D PhC). The topological edge state (TES) excited by the 1D PhC heterostructure significantly enhances the local electric field near the nonlinear 3D DSM, which provides a positive condition for the realization of low threshold OB. Through parameter optimization, we obtain a threshold electric field with an incident electric field of 106 V/m levels. Furthermore, the influences of the Fermi energy and thickness of 3D DSM and the angle of the incident light on the hysteretic behavior as well as the threshold of OB are clarified. 3D DSM-based optical devices with intrinsic OB provide a building block for future integrated optical and all-optical networks.

GSK3ß-dependent lysosome biogenesis: An effective pathway to mitigate renal fibrosis with LM49.

Renal fibrosis is an incurable disorder characterised by an imbalance of the extracellular matrix (ECM) favouring excess production over degradation. The identification of actionable pathways and agents that promote ECM degradation to restore ECM homeostasis may help mitigate renal fibrosis. In this study, we identified 5,2'-dibromo-2,4',5'-trihydroxydiphenylmethanone (LM49), a compound we previously synthesised, as a small-molecule inducer of ECM degradation. LM49 administration efficiently reduced ECM deposition in renal tissue of diabetic nephropathy rats and in transforming growth factor ß-treated renal fibroblast cells. LM49 promoted the cytosol-to-nucleus translocation of transcription factor EB (TFEB) to increase lysosome biogenesis, leading to lysosome-based degradation of the ECM. TFEB-mediated lysosome biogenesis was induced by LM49 directly inhibiting the activity of glycogen synthase kinase 3ß (GSK3ß) rather than mammalian target of rapamycin complex 1. LM49 inhibited GSK3ß kinase activity concentration-dependently via competing with ATP. Direct binding between LM49 and GSK3ß was confirmed by the bio-layer interferometry assay, cellular thermal shift assay, and drug affinity responsive target stability. A molecular docking and molecular dynamic simulation revealed that LM49 occupied the ATP pocket of GSK3ß, which was consistent with the kinase activity assay. In summary, LM49 enhances TFEB-mediated lysosome biogenesis by directly inhibiting GSK3ß, leading to the degradation of the ECM by lysosomes. The enhancement of GSK3ß-dependent lysosome biogenesis to rebalance the ECM may be a novel strategy to counteract renal fibrosis, and LM49 may be a viable clinical candidate for treating this disorder.

Improving endothelial cell junction integrity by diphenylmethanone derivatives at oxidative stress: A dual-action directly targeting caveolar caveolin-1.

Directly targeting caveolar caveolin-1 is a potential mechanism to regulate endothelial permeability, especially during oxidative stress, but little evidence on the topic limits therapeutics discoveries. In this study, we investigated the pharmacological effect of an antioxidant LM49 (5,2'-dibromo-2,4',5'-trihydroxydiphenylmethanoe) and its five diphenylmethanone derivatives on endothelial permeability and establish two distinct mechanisms of action. Multiplex molecular assays with theoretical modeling indicate that diphenylmethanone molecules, including LM49, directly bind the caveolin-1 steric pocket of ASN53/ARG54, ILE49/ASP50, ILE18, LEU59, ASN60, GLU48 and ARG19 residues. They also indicated dynamic binding-affinity for diphenylmethanone derivatives. First, this molecular interaction at caveolin-1 pocket inhibits its phosphorylation at TYR14 residue in H2O2-injured endothelial cell. A positive correlation was established between diphenylmethanone derivative binding-affinity and caveolin-1 phosphorylation inhibition. Inhibition of caveolin-1 phosphorylation, however, was independent of the LM49-mediated variation of protein tyrosine kinase activity, suggesting a direct blockage of adenosine triphosphate substrate diffusion into cavelion-1 structure. Second, LM49 increases the expression of cellular adhesive and tight junction proteins, VE-cadherin and occludin, in H2O2-injured cell, in a dose dependent manner. A leakage assay of fluorescein isothiocyanate-labeled dextran 40 across cell monolayer suggested improvement in endothelial barrier integrity with diphenylmethanone treatments. Our results demonstrate a direct targeting effect of caveolin-1 on endothelial permeability, and should guide the diphenylmethanone therapy against oxidative stress-induced junction dysfunction, especially at caveolar membrane invagination.

DnaJ, a promising vaccine candidate against Ureaplasma urealyticum infection.

Ureaplasma urealyticum (U. urealyticum, Uu) is a common sexually transmitted pathogen that is responsible for diseases such as non-gonococcal urethritis, chorioamnionitis, and neonatal respiratory diseases. The rapid emergence of multidrug-resistant bacteria threatens the effective treatment of Uu infections. Considering this, vaccination could be an efficacious medical intervention to prevent Uu infection and disease. As a highly conserved molecular chaperone, DnaJ is expressed and upregulated by pathogens soon after infection. Here, we assessed the vaccine potential of recombinant Uu-DnaJ in a mouse model and dendritic cells. Results showed that intramuscular administration of DnaJ induced robust humoral- and T helper (Th) 1 cell-mediated immune responses and protected against genital tract infection, inflammation, and the pathologic sequelae after Uu infection. Importantly, the DnaJ protein also induced the maturation of mouse bone marrow-derived dendritic cells (BMDCs), ultimately promoting naïve T cell differentiation toward the Th1 phenotype. In addition, adoptive immunization of DnaJ-pulsed BMDCs elicited antigen-specific Immunoglobulin G2 (IgG2) antibodies as well as a Th1-biased cellular response in mice. These results support DnaJ as a promising vaccine candidate to control Uu infections. KEY POINTS: • A novel recombinant vaccine was constructed against U. urealyticum infection. • Antigen-specific humoral and cellular immune responses after DnaJ vaccination. • Dendritic cells are activated by Uu-DnaJ, which results in a Th1-biased immune response.

Sound touch elastography for assessing cirrhosis preoperatively in infants with biliary atresia: Comparison with serum fibrosis biomarkers.

Introduction: The accurate assessment of the stages of hepatic fibrosis in children with biliary atresia (BA) before performing Kasai portoenterostomy (KPE) is of utmost importance. Some studies demonstrated that ultrasound elastography can be used to assess the stages of hepatic fibrosis by detecting liver stiffness. Therefore, the aim of this work was to explore the usefulness of sound touch elastography (STE) for preoperatively assessing liver cirrhosis in infants with BA. Methods: A total of 189 children from the Hunan Children's Hospital with highly suspected BA were selected for this study, and their preoperative liver STE values and related clinical data were collected. The pathological results of the liver stages were considered as the gold standard. Spearman correlation was used to analyze the correlation between each parameter and the stage of hepatic fibrosis, and the receiver operator characteristic (ROC) curve was used to analyze the diagnostic performance for cirrhosis of each parameter. Results: Among the selected 189 patients with suspected BA, 159 were included in this study and were composed of 3 at hepatic fibrosis stage F1, 45 at stage F2, 41 at stage F3, and 70 at stage F4, while no patients at stage F0 were present. Spearman correlation analysis showed that the liver STE value had the highest correlation with the stage of hepatic fibrosis, with a correlation coefficient of 0.813 (P < 0.001). The liver STE value had the highest diagnostic performance for hepatic cirrhosis compared to other biomarkers of serum fibrosis; the area under the ROC curve was 0.899 when the best cut-off value was 14.57 kPa. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 78.6, 84.3, 79.7, 83.3, and 81.8%, respectively. Conclusion: The liver STE value has a high correlation with the stage of hepatic fibrosis in children with BA. STE has a good diagnostic performance in evaluating cirrhosis before KPE in children with BA.

The role of tryptophan in Chlamydia trachomatis persistence.

Chlamydia trachomatis (C. trachomatis) is the most common etiological agent of bacterial sexually transmitted infections (STIs) and a worldwide public health issue. The natural course with C. trachomatis infection varies widely between individuals. Some infections clear spontaneously, others can last for several months or some individuals can become reinfected, leading to severe pathological damage. Importantly, the underlying mechanisms of C. trachomatis infection are not fully understood. C. trachomatis has the ability to adapt to immune response and persist within host epithelial cells. Indoleamine-2,3-dioxygenase (IDO) induced by interferon-gamma (IFN-γ) degrades the intracellular tryptophan pool, to which C. trachomatis can respond by converting to a non-replicating but viable state. C. trachomatis expresses and encodes for the tryptophan synthase (TS) genes (trpA and trpB) and tryptophan repressor gene (trpR). Multiple genes interact to regulate tryptophan synthesis from exogenous indole, and persistent C. trachomatis can recover its infectivity by converting indole into tryptophan. In this review, we discuss the characteristics of chlamydial infections, biosynthesis and regulation of tryptophan, the relationship between tryptophan and C. trachomatis, and finally, the links between the tryptophan/IFN-γ axis and C. trachomatis persistence.

A novel UBE2A splice site variant causing intellectual disability type Nascimento.

X-linked intellectual disability type Nascimento (XLID) is a rare disease caused by variants in the ubiquitin-conjugating enzyme E2A gene (UBE2A). Patients with XLID have similar phenotypes, including speech impairments, severe intellectual disability, hearing loss, wide facies, synophrys, generalized hirsutism, and urogenital abnormalities. Till date, only two splice-site variants of the UBE2A gene have been observed in patients with X-linked ID type Nascimento. Here, we report the case of a Chinese boy with a syndrome clinically similar to XLID with speech impairment, severe intellectual disability, and moderate hearing loss. However, different characteristics were also present in the patient, including an inability to maintain his head in an upright posture. Both of the patient's palms have a single transverse palmar crease. Subsequent whole-exome sequencing revealed a novel splice site variant in UBE2A (c.241 + 1 G > A). Our study not only expands the variant spectrum and clinical characteristics of UBE2A deficiency syndrome but also provides clinical evidence for genetic diagnoses.

Neddylation Inhibition Causes Impaired Mouse Embryo Quality and Blastocyst Hatching Failure Through Elevated Oxidative Stress and Reduced IL-1ß.

Mammalian blastocyst hatching is an essential prerequisite for successful embryo implantation. As the rate-limiting step of current assisted reproductive technology, understanding the key factors regulating blastocyst hatching would be significantly helpful to improve the performance of the assisted reproductive practice. In early embryo development, the fine-tuned elimination of maternal materials and the balanced protein turnover are inevitable for the competent to hatch and implant into endometrium. Neddylation, a ubiquitination-like protein modification, has been shown to be involved in oocyte maturation and early embryo development. In this study, aiming to discover an unknown role of neddylation in the blastocyst hatching process, we provided functional evidence of neddylation in mammalian embryo quality and blastocyst hatching. Treatment with MLN4924, a specific neddylation inhibitor, lowered the embryo quality and dramatically reduced the hatching rate in mouse blastocysts. The transcriptional profile showed the upregulation of oxidative stress-related genes and aberrant expression of immune-related genes. The elevated oxidative stress was validated by qPCR and markers of apoptosis, DNA damage, reactive oxygen species, and cytoskeleton. Moreover, we found the secreted IL-1ß level was reduced in an NF-κB-independent manner, leading to the final poor embryo quality and blastocyst hatching failure. This is the first report of neddylation being of great importance in the mammalian blastocyst hatching process. Further investigations uncovering more detailed molecular mechanisms of neddylation regulation in blastocyst hatching would greatly promote not only the understanding of this crucial biological process but also the clinical application in reproductive centers.

5,2'-Dibromo-2,4',5'-trihydroxydiphenylmethanone Inhibits LPS-Induced Vascular Inflammation by Targeting the Cav1 Protein.

Vascular inflammation is directly responsible for atherosclerosis. 5,2'-Dibromo-2,4',5'-trihydroxydiphenylmethanone (TDD), a synthetic bromophenol derivative, exhibits anti-atherosclerosis and anti-inflammatory effects. However, the underlying pathways are not yet clear. In this study, we first examined the effects of TDD on toll-like receptor-4 (TLR4) activity, the signaling receptor for lipopolysaccharide (LPS), and found that TDD does not inhibit LPS-induced TLR4 expression in EA.hy926 cells and the vascular wall in vivo. Next, we investigated the global protein alterations and the mechanisms underlying the action of TDD in LPS-treated EA.hy926 cells using an isobaric tag for the relative and absolute quantification technique. Western blot analysis revealed that TDD inhibited NF-κB activation by regulating the phosphorylation and subsequent degradation IκBα. Among the differentially expressed proteins, TDD concentration-dependently inhibited Caveolin 1(Cav1) expression. The interaction between Cav1 and TDD was determined by using biolayer interference assay, UV-vis absorption spectra, fluorescence spectrum, and molecular docking. We found that TDD can directly bind to Cav1 through hydrogen bonds and van der Waals forces. In conclusion, our results showed that TDD inhibited LPS-induced vascular inflammation and the NF-κB signaling pathway by specifically targeting the Cav1 protein. TDD may be a novel anti-inflammatory compound, especially for the treatment of atherosclerosis.

Target-Sequencing of Female Infertility Pathogenic Gene Panel and a Novel TUBB8 Loss-of-Function Mutation.

Genetic screening is an important approach for etiology determination and helps to optimize administration protocols in reproductive centers. After the first pathogenic gene of female infertility was reported in 2016, more and more new pathogenic genes were discovered, and we sought to develop an efficient and cost-effective method for genetic screening in patients. In this study, we designed a target-sequencing panel with 22 female infertility-related genes, namely, TUBB8, PATL2, WEE2, and PANX1 and sequenced 68 primary infertility (PI) and recurrent pregnancy loss (RPL) patients. We sequenced 68 samples reaching an average depth of 1559× and detected 3,134 variants. Among them, 62.2% were synonymous single-nucleotide variants (SNVs) and 36.3% were non-synonymous SNVs. The remaining 1.5% are indels (insertions and deletions) and stop-gains. DNAH11 and TUBB8 are the two genes that mutated most frequently. We also found a novel TUBB8 variant (c.898_900del; p.300_300del), proved its loss-of-function mechanism, and profiled the interactome of the wild-type (WT) and mutant TUBB8 proteins. Overall, this target-sequencing method provides an efficient and cost-effective approach for screening in IVF clinics and will support researchers for the discovery of new pathogenic variants.

Occurrence of Root-Lesion Nematode Pratylenchus coffeae on Corn in Xinjiang Uygur Autonomous Region, China.

Pratylenchus coffeae Filipjev & Schuurmans Stekhoven, 1941, is one of the most important root-lesion nematodes (RLN) parasitizing many agronomic and industrial crops (Wang et al. 2021). Corn (Zea mays L.) is one economically important crop in China, with 35 million hectares cultivated annually (Li et al. 2019). In July 2019, a survey of RLN was carried out in corn field planting with cultivar Heyu 187 in Chuanba village in Qitai County, Xinjiang Uygur Autonomous Region, China. Five root/soil samples were collected from poor growing plants with distinct brown lesions. Nematodes were extracted from the collected root/soil samples with the modified Baermann funnel method (Hooper et al. 2005). The average of 157 RLN per 100 cm3 of soil and 43 RLN per gram of fresh root were extracted. The obtained RLN were sterilized with 0.3% streptomycin sulfate and cultured on carrot disks at 25°C. Twenty petri dishes with carrot disks, each inoculated with one female. The morphological and molecular characteristics of RLN cultured on carrot disks were examined for species identification. Morphological measurements of adult females (n=15) included body length (range = 529.0 to 658.0 µm, mean = 571.0 µm), head with two lip annuli, stylet (15.5 to 17.0 µm, 16.0 µm), tail length (27.5 to 32.5 µm, 30.5 µm), a (23.8 to 32.9, 28.5), b (5.8 to 7.1, 6.5), c (16.5 to 23.4, 18.9), and V (76.6 to 83.1%, 80.8%). Morphological measurements of adult males (n=15) were body length (range = 479.5 to 568.0 µm, mean = 516.0 µm), head with two lip annuli, stylet (14.5 to 15.5 µm, 15.0 µm), tail length (24.0 to 29.0 µm, 26.0 µm), spicule length (16.4 to 19.0 µm, 17.5 µm), gubernaculum length (4.4 to 5.3 µm, 4.9 µm), a (29.2 to 32.5, 31.0), b (5.7 to 6.9, 6.2), and c (18.2 to 22.6, 19.8). The morphological characters of this population are consistent with the description of P. coffeae (Castillo and Vovlas, 2007). Nematode DNA was extracted from an individual female. The primers of D2A/D3B (5'-ACAAGTACCGTGAGGGAAAGTTG-3'/5'-TCGGAAGGAACCAGCTACTA-3') (Subbotin et al. 2006) and 18S/26S (5'-TTGATTACGTCCCTGCCCTTT-3' / 5'-TTTCACTCGCCGTTACTAAGG-3') (Vrain et al. 1992) were used to amplify the D2/D3 expansion region of the 28S rRNA gene and the rDNA internal transcribed spacer (ITS) region, respectively. The PCR products were purified and transformed to E. coli strain DH5α, and then sequenced by Sangon Biotech Co. Ltd. (Shanghai, China). The obtained sequences of the D2/D3 region (793 bp) and the ITS region (1,242 bp) were submitted to GenBank, and the accession numbers for D2/D3 region were OK103614 and OK103619 which had 98.6% and 100% identity with the reported P. coffeae sequences (KC490925); the two obtained ITS sequences accession numbers OK103603 and OK103613) had more than 99% identity with published P. coffeae sequences from GenBank (e.g., LC030410, LC030395, MH134508 and LC030380). Hence, both morphological and molecular data demonstrated the presence of P. coffeae. To further confirm reproduction on corn, the obtained RLN population was used to inoculate corn plants in 2-liter pots containing 1.8-liter sterilized and mixed soil with 2 pastoral soil: 1 substrate in greenhouse at 27°C. About 15 days after sowing, each pot with one corn plant (cv. Heyu 187) with the same growth status was selected to inoculate P. coffeae. Five small holes near the roots were made using a glass rod. Approximately 1,000 mixed stage nematodes of P. coffeae were then pipetted into the holes of each plant. Eight replications were performed. Eight additional pots of uninoculated corn plants were used as control. After 2 months, corn roots were washed and brown lesions were observed on roots. The average number of RLN/pot was approximately 5,030 in soil and 2,870 in roots, and each pot had an average of 7.9 reproduction factors (final population/initial population), indicating that this nematode population infects and reproduces well on this corn cultivar. No nematodes and symptoms was detected in the control pot. The nematode of P. coffeae has only been reported on corn in Guangdong, Liaoning, Shangdong and Henan Provinces in China (Liu et al. 1996; Liu et al. 2001; Xia et al. 2021). To our knowledge, this is the first report of P. coffeae infecting corn in Xinjiang Uygur Autonomous Region of China. Since RLN can cause considerable damage to corn, one of the most important food crops produced in China, strategic measures should be taken to prevent the spread of P. coffeae to other regions.

A novel effector, CsSp1, from Bipolaris sorokiniana, is essential for colonization in wheat and is also involved in triggering host immunity.

The hemibiotrophic pathogen Bipolaris sorokiniana causes root rot, leaf blotching, and black embryos in wheat and barley worldwide, resulting in significant yield and quality reductions. However, the mechanism underlying the host-pathogen interactions between B. sorokiniana and wheat or barley remains unknown. The B. sorokiniana genome encodes a large number of uncharacterized putative effector proteins. In this study, we identified a putative secreted protein, CsSp1, with a classic N-terminal signal peptide, that is induced during early infection. A split-marker approach was used to knock out CsSP1 in the Lankao 9-3 strain. Compared with the wild type, the deletion mutant ∆Cssp1 displayed less radial growth on potato dextrose agar plates and produced fewer spores, and complementary transformation completely restored the phenotype of the deletion mutant to that of the wild type. The pathogenicity of the deletion mutant in wheat was attenuated even though appressoria still penetrated the host. Additionally, the infectious hyphae in the deletion mutant became swollen and exhibited reduced growth in plant cells. The signal peptide of CsSp1 was functionally verified through a yeast YTK12 secretion system. Transient expression of CsSp1 in Nicotiana benthamiana inhibited lesion formation caused by Phytophthora capsici. Moreover, CsSp1 localized in the nucleus and cytoplasm of plant cells. In B. sorokiniana-infected wheat leaves, the salicylic acid-regulated genes TaPAL, TaPR1, and TaPR2 were down-regulated in the ∆Cssp1 strain compared with the wild-type strain under the same conditions. Therefore, CsSp1 is a virulence effector and is involved in triggering host immunity.

High Sensitivity Terahertz Biosensor Based on Mode Coupling of a Graphene/Bragg Reflector Hybrid Structure.

In this work, a high-sensitivity terahertz (THz) biosensor is achieved by using a graphene/Bragg reflector hybrid structure. This high-sensitivity THz biosensor is developed from the sharp Fano resonance transmission peak created by coupling the graphene Tamm plasmons (GTPs) mode to a defect mode. It is found that the proposed THz biosensor is highly sensitive to the Fermi energy of graphene, as well as the thickness and refractive index of the sensing medium. Through specific parameter settings, the composite structure can achieve both a liquid biosensor and a gas biosensor. For the liquid biosensor, the maximum sensitivity of > 1000 °/RIU is obtained by selecting appropriate parameters. We believe the proposed layered hybrid structure has the potential to fabricate graphene-based high-sensitivity biosensors.