Potential Biocontrol Microorganisms Causing Attenuated Pathogenicity in Plasmopara viticola.

A phenomenon of pathogenicity attenuation of Plasmopara viticola was consistently observed during its subculture on grape. To clarify the causes of attenuated pathogenicity of P. viticola, culturable microbes were isolated from the P. viticola mass (mycelia, sporangiophores, and sporangia) in each generation and tested for their biocontrol efficacies on grape downy mildew (GDM). The results showed that the incidence of GDM decreased with the increase in the number of subculture times on both vineyard-collected leaves and grape leaves from in vitro-grown seedlings. The number of culturable microbial taxa on the surface of P. viticola decreased, whereas the population densities of four specific strains (i.e., K2, K7, P1, and P5) increased significantly with the increase in subculture times. Compared with the control, the biocontrol efficacies of the bacterial strain K2 reached 87.5%, and those of both fungal strains P1 and P5 reached 100.0%. Based on morphological characteristics and molecular sequences, strains K2, P1, and P5 were identified as Curtobacterium herbarum, Thecaphora amaranthi, and Acremonium sclerotigenum, respectively, and these three strains survived very well and multiplied on the surface of P. viticola. As the number of times P. viticola was subcultured increased, all three of these strains became the predominant strains, leading to greater P. viticola inhibition, attenuated P. viticola pathogenicity, and effective GDM biological control. To the best of our knowledge, this is the first report of C. herbarum and T. amaranthi having biological control activity against GDM.

Peptide-free Synthetic Nicotine Vaccine Candidates with α-Galactosylceramide as Adjuvant.

Peptides are generally needed as T-helper epitopes in nicotine vaccines to induce effective antibody responses, but the highly polymorphic property of major histocompatibility complex (MHC) molecules may limit opportunities of B cell to receive CD4+ T-cell help. Invariant natural killer T (iNKT) cells recognize lipid antigens presented by the nonpolymorphic CD1d molecule that is conserved in mammals to a great extent. iNKT cells also display some similar functions to conventional CD4+ T-helper cells, especially they license dendritic cells stimulate antibody isotype switching by B cells. Herein, α-galactosylceramide (αGalCer), a classical iNKT cell agonist, serves as an adjuvant in synthetic nicotine vaccine candidates absent of peptide or protein. Our study reveals that αGalCer displays better adjuvant activity than Pam3CSK4 (a commonly used lipopeptide TLR agonist). Remarkably, the covalent linker between the nicotine hapten and αGalCer is not critical. Self-assembly of the lipid-tailed nicotine and αGalCer into the liposome represents a structurally simple but immunologically effective way to develop nicotine vaccines. This is the first time to introduce the iNKT cell agonist as an adjuvant to an antidrug vaccine. This discovery may contribute to improving the efficacy of clinical candidate nicotine vaccines in the future.

[Identification of a novel CRYGC mutation in a pedigree affected with congenital cataracts].

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with congenital cataracts. METHODS: Clinical data and peripheral blood samples were collected for the pedigree. Following extraction of genomic DNA, whole exome sequencing was carried out to detect genetic variants. Candidate variants were verified by familial co-segregation analysis and Sanger sequencing. Bioinformatics analysis was carried out to predict the function of mutant genes. RESULTS: By comparing variants identified among affected and unaffected individuals, a heterozygous variant, c.110 G>C (p.R37P), was identified in exon 2 of the CRYGC gene among all patients, which also matched the criteria for potential disease-causing mutations. The result was confirmed by Sanger sequencing. CONCLUSION: The c.110G>C variant of the CRYGC gene probably underlay the congenital cataracts in this pedigree.

Performance of preimplantation genetic testing for aneuploidy for patients with unexplained recurrent pregnancy loss and repeated implantation failure.

Objective: The primary objective was to investigate whether the utilization of next-generation sequencing (NGS) for preimplantation genetic testing for aneuploidy (PGT-A) could enhance the reproductive outcomes in patients with unexplained recurrent pregnancy loss (uRPL) or unexplained repeated implantation failure (uRIF) undergoing intracytoplasmic sperm injection (ICSI) cycles. Materials and methods: We studied the reproductive outcomes of uRPL or uRIF sufferers in Chengdu women and children's central hospital from July 2020 to Jan 2024 retrospectively. These patients were categorized into two groups based on whether they underwent PGT-A or not. As the patients in the PGT-A group all had ICSI and frozen-thawed embryo transfer (FET), only patients who underwent ICSI and FET were included in the non-PGT-A group for comparison. Demographic characteristics and reproductive outcomes were compared in uRPL or uRIF sufferers. Results: For uRPL group, a significant increased ongoing pregnancy rate (63.6 % vs 26.1 %, p = 0.002) and reduced pregnancy loss rate (18.4 % vs 73.3 %, p < 0.001) were found in the PGT-A group in comparison with those in the non-PGT-A group. For uRIF group, no significant difference was noted in the HCG-positive rate, ongoing pregnancy rate, or pregnancy loss rate between the two groups. It is noteworthy that the maternal age in the PGT-A group was significantly higher than that in the non-PGT-A group (p = 0.048). Conclusions: NGS-based PGT-A effectively optimized the reproductive outcomes in uRPL sufferers. Although its benefits in uRIF appeared to be limited, there is a potential advantage for those with advanced maternal age. Considering the small sample size, further randomized controlled trials are warranted to validate these findings.

Does endometrial receptivity array improve reproductive outcomes in euploid embryo transfer cycles? a systematic review.

Besides chromosomal normality, endometrial receptivity is an important factor in determining successful pregnancies. Endometrial receptivity array (ERA), a promising endometrial receptivity test, was speculated to improve the reproductive outcomes. However, its effectiveness is controversial in clinical practice. Therefore, we conducted this review to investigate its role in in vitro fertilization (IVF) treatment. To eliminate the interference of embryo quality, we only analyzed studies that originally reported the reproductive outcomes of patients who underwent ERA-guided euploid embryo transfer (EET). Unexpectedly, it revealed that ERA could not optimize the reproductive outcomes in EET cycles, no matter in general infertile population or in patients with a history of previous failed embryo transfers.

Potent Neutralizing Antibodies Elicited by RBD-Fc-Based COVID-19 Vaccine Candidate Adjuvanted by the Th2-Skewing iNKT Cell Agonist.

The development of a safe and effective COVID-19 vaccine is of paramount importance to terminate the current pandemic. An adjuvant is crucial for improving the efficacy of the subunit COVID19 vaccine. α-Galactosylceramide (αGC) is a classical iNKT cell agonist which causes the rapid production of Th1- and Th2-associated cytokines; we, therefore, expect that the Th1- or Th2-skewing analogues of αGC can better enhance the immunogenicity of the receptor-binding domain in the spike protein of SARS-CoV-2 fused with the Fc region of human IgG (RBD-Fc). Herein, we developed a universal synthetic route to the Th1-biasing (α-C-GC) and Th2-biasing (OCH and C20:2) analogues. Immunization of mice demonstrated that αGC-adjuvanted RBD-Fc elicited a more potent humoral response than that observed with Alum and enabled the sparing of antigens. Remarkably, at a low dose of the RBD-Fc protein (2 µg), the Th2-biasing agonist C20:2 induced a significantly higher titer of the neutralizing antibody than that of Alum.

PKM2 upregulation promotes malignancy and indicates poor prognosis for intrahepatic cholangiocarcinoma.

BACKGROUND: Although pyruvate kinase M2 (PKM2) has been shown to be among the crucial enzymes that regulate aerobic glycolysis in multiple tumour cells, its role in the treatment and prognosis of intrahepatic cholangiocarcinoma (ICC) remains unclear. This study primarily aimed to determine whether the expression status of PKM2 is potentially associated with the clinical outcomes of ICC. METHODS: PKM2 expression was evaluated in ICC cell lines and tissues via real-time quantitative reverse-transcription polymerase chain reaction, immunofluorescence assays, and Western blot, and its prognostic value was determined according to its impact on the overall survival of patients. RESULTS: We found that PKM2 is highly expressed in ICC, and this was correlated with patient survival. Moreover, we found that PKM2 knockdown could considerably inhibit ICC cell proliferation, invasion, and migration in vitro. CONCLUSIONS: PKM2 was overexpressed in ICC, and it may regulate proliferation, invasion, and migration and lead to poor prognosis. Thus, PKM2 might be a potential independent prognostic factor for ICC.

A primary splenic angiosarcoma hepatic metastasis after splenectomy and its genomic alteration profile.

RATIONALE: Primary splenic angiosarcoma (PSA) is a rare mesenchymal malignancy of the splenic vascular origin often with a dismal prognosis. Genomic profile may provide evidence for the solution of therapy. PATIENT CONCERNS: We reported a case of a 51-year-old woman with splenectomy 4 years ago and the postoperative histopathology diagnosis revealed "splenic hemangioma" with spontaneous rupture. Two years after the operation, the patient's rechecked abdominal computed tomography (CT) showed multiple hepatic occupations. DIAGNOSES: Pathological test suggested PSA hepatic metastasis. INTERVENTIONS: The patient was treated with trans-catheter arterial chemoembolization (TACE) and a pathological diagnosis of PSA was highly suspected in the hepatic biopsy. Four somatic alterations, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), Fos proto-oncogene, AP-1 transcription factor subunit (FOS), MCL1 apoptosis regulator (MCL1), and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) were detected in the tumor tissue using a Next generation sequencing (NGS) technology. The results prompted that the patient may get clinical benefit from using some agents for targeted therapy, Everolimus, Temsirolimus, or Copanlisib. OUTCOMES: The patient refused targeted therapy. As a result, the patient passed away within 51 months after splenectomy. LESSONS: PSA is an aggressive disease that often presented with a high propensity for metastasis and rupture hemorrhage. Some of these mutations were first discovered in PSA and these findings added new contents to the genomic mutation profile of PSA.

Bilateral Common Carotid Artery Occlusion in Spontaneously Hypertensive Rats: A Feasible Animal Model for Ocular Ischemic Syndrome.

The purpose of this study was to investigate the feasibility of inducing ocular ischemic syndrome in spontaneously hypertensive rats. Hypertensive and normotensive Wistar-Kyoto rats had bilateral occlusion or sham surgery. They were divided into 4 groups: (1) hypertensive-ischemia, (2) hypertensive-sham, (3) normotensive-ischemia, and (4) normotensive-sham. Four months after the operation, the global changes of the eye and pupillary light reflex were assessed. Then each rat was perfused, and randomly one of the bulbuses oculi was prepared as retinal flat mounts for investigation of vascular changes. The opposite eyeball was prepared as a paraffin section for observation of the linear density of retinal ganglion cells and for thickness measurement. One hypertensive-ischemia rat had a cataract in one eye and another rat in the same group had bulbus oculi collapse in one eye. The light reflex disappeared in 13.33% of hypertensive-ischemia rats, and the rest of the hypertensive-ischemia rats and normotensive-ischemia rats had slow reflex. Compared with the respective controls, the peripheral retinal vascular network in hypertensive-ischemia and normotensive-ischemia rats was sparse; linear density of the retinal ganglion cells was significantly reduced; and the retinal thickness was reduced. Compared with normotensive-ischemia rats, the hypertensive-ischemia rats demonstrated more severe changes. After bilateral common carotic artery occlusion, the eyes of hypertensive rats developed various pathological changes similar to those of ocular ischemic syndrome. In conclusion, an animal model for ocular ischemic syndrome can be created by bilateral common carotid artery occlusion in spontaneously hypertensive rats. Anat Rec, 299:806-814, 2016. © 2016 Wiley Periodicals, Inc.

Late postpartum eclampsia complicated with posterior reversible encephalopathy syndrome: a case report and a literature review.

Posterior reversible encephalopathy syndrome (PRES) is a rare but serious clinical-neuroradiological entity characterized by headache, vomiting, visual disturbances, altered mental status, seizures, and unconsciousness associated with the characteristic imaging findings including sub-cortical vasogenic edema at the bilateral parietal and occipital lobes. We describe a case of 28-year-old PRES patient secondary to delayed maternal postpartum eclampsia. This patient was not initially diagnosed with pre-eclampsia and PRES. The diagnosis was established after magnetic resonance imaging. After treatment this patient's PRES resolved. Early diagnosis and treatment are the keys to reverse PRES. A literature review for PRES is provided in this report.

Incidence and risk factors of retinopathy of prematurity in two neonatal intensive care units in North and South China.

BACKGROUND: To investigate the incidence and risk factors of retinopathy of prematurity (ROP) in two Neonatal Intensive Care Units in North and South of China, respectively. METHODS: We studied data concerning 472 infants with gestational age (GA) ≤ 34 weeks or birth weight (BW) ≤ 2000 g who were admitted to the Zhujiang Hospital of Southern Medical University and the Fourth Hospital of Shijiazhuang between January 1, 2011 and December 31, 2011. Clinical information about perinatal neonates was collected and was confirmed by reviewing medical charts. The incidence and severity of ROP were assessed in the screened population. Main outcome measures are the incidence and severity of ROP. The relationship of clinical risk factors and the development of ROP were analyzed. RESULTS: The overall incidence of ROP was 12.7%, and the overall incidence of type 1 ROP was 2.3%; 9.4% of infants in Zhujiang Hospital had ROP compared to 15.0% infants in the Fourth Hospital of Shijiazhuang developed ROP, and the difference is statistically significant. ROP was significantly associated with GA (odds ratio [OR]: 0.77 [0.62-0.95], P = 0.015), BW (OR: 0.998 [0.996-0.999], P = 0.008), maternal supplemental oxygen administration before and during delivery (OR: 4.27 [1.21-15.10], P = 0.024) and preeclampsia (OR: 6.07 [1.73-21.36] P = 0.005). The risk factors for ROP are different in two hospitals. In Zhujiang Hospital, BW is the independent risk factors for ROP while GA, BW and preeclampsia in the Fourth Hospital in Shijiazhuang Conclusions: Retinopathy of prematurity incidence is different based on area. Incidence of ROP is still high in China. More efforts need to prevent ROP.