WD repeat domain 5 promotes the development of late-onset preeclampsia by activating nuclear factor kappa B.

PURPOSE: Over-activation of nuclear factor kappa B (NF-κB) was proven to be involved in the pathogenesis of preeclampsia. However, its regulation mechanism is not clear yet. This paper explored the role of WD repeat domain 5 (WDR5) in the development of late-onset preeclampsia and its relationship with NF-κB. METHODS: WDR5 expression was detected in normal placentas and placentas from late-onset preeclampsia patients. CCK-8 and colony formation assays were conducted to appraise the proliferative ability of trophoblast. Migration and invasion were observed by wound healing and transwell assays. The interaction between WDR5 and NF-κB inhibitor I-kappa-B-alpha (IkBa) was verified by Co-immunoprecipitation analysis. Immunofluorescence was used to analyze the activation of NF-κB. Finally, we tested the role of WDR5 using the mice late-onset preeclampsia model. RESULTS: WDR5 was highly expressed in the placentas of late-onset preeclampsia patients. WDR5 overexpression suppressed cell proliferation, migration, and invasion in trophoblast. WDR5 could interact with IkBa to activate NF-κB. Knockdown of NF-κB counteracted the anti-proliferative and anti-metastatic effects of WDR5 overexpression in trophoblast. In-vivo studies suggested that targeting WDR5 combated late-onset preeclampsia development. CONCLUSIONS: Our finding provides new insights into the role of WDR5 in late-onset preeclampsia development.

Prediction of Prognosis and Immunotherapy Response with a Novel Natural Killer Cell Marker Genes Signature in Osteosarcoma.

Background: Natural killer (NK) cells are characterized by their antitumor efficacy without previous sensitization, which have attracted attention in tumor immunotherapy. The heterogeneity of osteosarcoma (OS) has hindered therapeutic application of NK cell-based immunotherapy. The authors aimed to construct a novel NK cell-based signature to identify certain OS patients more responsive to immunotherapy. Materials and Methods: A total of eight publicly available datasets derived from patients with OS were enrolled in this study. Single-cell RNA sequencing data obtained from the Gene Expression Omnibus (GEO) database were analyzed to screen NK cell marker genes. Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis was used to construct an NK cell-based prognostic signature in the TARGET-OS dataset. The differences in immune cell infiltration, immune system-related metagenes, and immunotherapy response were evaluated among risk subgroups. Furthermore, this prognostic signature was experimentally validated by reverse transcription-quantitative real-time PCR (RT-qPCR). Results: With differentially expressed NK cell marker genes screened out, a five-gene NK cell-based prognostic signature was constructed. The prognostic predictive accuracy of the signature was validated through internal clinical subgroups and external GEO datasets. Low-risk OS patients contained higher abundances of infiltrated immune cells, especially CD8 T cells and naive CD4 T cells, indicating that T cell exhaustion states were present in the high-risk OS patients. As indicated from correlation analysis, immune system-related metagenes displayed a negative correlation with risk scores, suggesting the existence of immunosuppressive microenvironment in OS. In addition, based on responses to immune checkpoint inhibitor therapy in two immunotherapy datasets, the signature helped predict the response of OS patients to anti-programmed cell death protein 1 (PD-1) or anti-programmed cell death ligand 1 (PD-L1) therapy. RT-qPCR results demonstrated the roughly consistent relationship of these five gene expressions with predicting outcomes. Conclusions: The NK cell-based signature is likely to be available for the survival prediction and the evaluation of immunotherapy response of OS patients, which may shed light on subsequent immunotherapy choices for OS patients. In addition, the authors revealed a potential link between immunosuppressive microenvironment and OS.

Preeclampsia-associated lncRNA FEZF1-AS1 regulates cell proliferation and apoptosis in placental trophoblast cells through the ELAVL1/NOC2L axis.

BACKGROUND: LncRNAs have been shown to be involved in and control the biological processes of multiple diseases, including preeclampsia (PE). The impairment of trophoblast cell proliferation is recognized as a significant anomaly contributing to the development of PE. LncRNA FEZF1-AS1 was found downregulated in placental tissues of PE patients. However, the precise regulatory mechanism of FEZF1-AS1 in placental trophoblast proliferation and apoptosis remains unclear. RESULTS: In this study, we conducted an investigation into the expression levels of FEZF1-AS1 and NOC2L in placental tissues obtained from patients diagnosed with PE. Subsequently, we employed CCK-8 and EdU assays to quantify cell proliferation, while TUNEL staining and western blot for apoptosis-related protein detection to assess apoptosis. Furthermore, the interactions between FEZF1-AS1 and ELAVL1, as well as NOC2L and ELAVL1, were confirmed through the implementation of RIP and RNA pull-down assays. We found a downregulation of lncRNA FEZF1-AS1 and NOC2L in placental tissues of PE patients. Overexpression of FEZF1-AS1 or NOC2L resulted in increased cell proliferation and inhibition of apoptosis, whereas knockdown of FEZF1-AS1 or NOC2L had the opposite effect. In addition, lncRNA FEZF1-AS1 stabilized NOC2L mRNA expression by interacting with ELAVL1. Moreover, partial reversal of the effects of FEZF1-AS1 overexpression on cell proliferation and apoptosis was observed upon suppression of ELAVL1 or NOC2L. CONCLUSIONS: PE related lncRNA FEZF1-AS1 could regulate apoptosis and proliferation of placental trophoblast cells through the ELAVL1/NOC2L axis.

miR-101-3p contributes to the progression of preeclampsia by suppressing WDR5-mediated proliferation and invasion of trophoblast.

BACKGROUND: Decreased proliferation and invasion of trophoblast were proven to be involved in the pathogenesis of preeclampsia (PE). However, the regulatory network has not been clarified yet. This study aimed to explore the role of miR-101-3p in the progression of PE. METHODS: miR-101-3p expression in placentas of pregnant women with or without PE was analyzed by real-time quantitative PCR (RT-qPCR). Trophoblastic HTR-8/SVneo and HPT-8 cell lines were cultured and underwent hypoxia/reoxygenation (H/R) treatment to mimic PE in vitro. Cell proliferation and invasion were analyzed in gain-of and loss-of-function assays. Finally, we undertook in vivo studies to explore effects of miR-101-3p in the PE model. RESULTS: Compared to placentas from patients without PE, miR-101-3p expressed significantly higher in placentas from PE patients, and its level was positively correlated with the severity of patients. In vitro studies found that overexpression of miR-101-3p significantly suppressed cell proliferation and invasion, while knockdown of miR-101-3p reversed the impacts of H/R treatment. Further research showed that the expression of WD repeat domain 5 (WDR5) was significantly lower in placentas from patients with PE, and its level was negatively associated with the severity of patients. In vitro and in vivo studies confirmed that miR-101-3p promoted PE progression through the regulation of WD WDR5 expression. CONCLUSION: Increased expression of miR-101-3p in placenta contributes to the development of PE by suppressing WDR5-mediated proliferation and invasion of trophoblast.

WD repeat domain 5 promotes the development of late-onset preeclampsia by activating nuclear factor kappa B

Purpose: Over-activation of nuclear factor kappa B (NF-κB) was proven to be involved in the pathogenesis of preeclampsia. However, its regulation mechanism is not clear yet. This paper explored the role of WD repeat domain 5 (WDR5) in the development of late-onset preeclampsia and its relationship with NF-κB. Methods: WDR5 expression was detected in normal placentas and placentas from late-onset preeclampsia patients. CCK-8 and colony formation assays were conducted to appraise the proliferative ability of trophoblast. Migration and invasion were observed by wound healing and transwell assays. The interaction between WDR5 and NF-κB inhibitor I-kappa-B-alpha (IkBa) was verified by Co-immunoprecipitation analysis. Immunofluorescence was used to analyze the activation of NF-κB. Finally, we tested the role of WDR5 using the mice late-onset preeclampsia model. Results: WDR5 was highly expressed in the placentas of late-onset preeclampsia patients. WDR5 overexpression suppressed cell proliferation, migration, and invasion in trophoblast. WDR5 could interact with IkBa to activate NF-κB. Knockdown of NF-κB counteracted the anti-proliferative and anti-metastatic effects of WDR5 overexpression in trophoblast. In-vivo studies suggested that targeting WDR5 combated late-onset preeclampsia development. Conclusions: Our finding provides new insights into the role of WDR5 in late-onset preeclampsia development.

Modified fixation for periprosthetic supracondylar femur fractures: Two case reports and review of the literature.

BACKGROUND: Periprosthetic supracondylar femoral fractures (PSFs) present a challenge in terms of optimizing fixation in patients with poor bone quality. Surgical treatment and peri-operative management of PSFs in the elderly remain a burden for orthopedic surgeons. Among different treatment options, locking plate (LP) and retrograde intramedullary nail (RIMN) have shown favorable results. However, reduced mobility and protected weight-bearing are often present in the postoperative older population. With a purpose of allowing for early weight-bearing, a modified nail plate combination (NPC) was redesigned for PSF management. CASE SUMMARY: In our cases, two elderly osteoporotic female underwent total knee arthroplasty (TKA), and then suffered from low energy trauma onto their knees after falling to the floor. Plain radiographs or computed tomography scans demonstrated oblique or transverse PSFs, both of which occurred at the distal femur above TKA. The modified NPC technique was performed for treatment of PSFs. The patient was made foot flat weight bearing in 1 wk. At 6-mo follow-up, the union was ultimately achieved using modified NPC with satisfactory implant outcomes. CONCLUSION: Neither LP nor RIMN alone may provide adequate support to allow for union in circumstances where the patient has severely osteopenic bone. Therefore, developing a modified implant offer an alternative choice for treating PSFs. These two cases revealed that this technique is a viable option for the geriatric osteoporotic PSFs, offering safe, early weight bearing and favorable clinical outcomes.

Case report of a delayed iatrogenic Pipkin type III femoral head fracture-dislocation.

RATIONALE: Pipkin III femoral head fracture dislocation (FHFD) is rarely observed in clinical practice, and its outcome is alarming. A considerable proportion of Pipkin III fractures result from repeated or forceful closed reduction of an irreducible FHFD. Pipkin type III fractures pose a therapeutic challenge. Most patients underwent total hip arthroplasty. PATIENT CONCERNS: A 34-year-old man experienced high-energy trauma to the left hip from a terrible traffic accident. Radiography and computed tomography (CT) at the local hospital revealed a left posterior FHFD. Emergency close reduction of the hip was performed.48 hours later, the patient was transferred to our institution. New radiography and CT examinations demonstrated an iatrogenic femoral neck fracture (FNF) associated with FHFD. In addition, a right talar fracture was observed. DIAGNOSIS: Pipkin III fracture combined with contralateral talar fracture. INTERVENTIONS: Considering his Pipkin fracture classification (Pipkin Type-III) and the time to surgery after his injury (>48 hours), the patient underwent left total hip arthroplasty uneventfully, followed by below-ankle plaster cast immobilization for his right ankle. OUTCOMES: At the 6-month follow-up, the patient was able to walk pain-free, and plain radiographs were satisfactory, with no evidence of heterotopic ossification or osteonecrosis of the talus. LESSONS: Before emergency closed reduction, early recognition of the unique characteristics of an irreducible FHFD is essential to avoid iatrogenic femoral neck fracture.

Efficacy of intrauterine Bakri balloon tamponade combined with ascending uterine artery ligation on postpartum hemorrhage.

OBJECTIVE: To observe the efficacy of intrauterine Bakri balloon tamponade (IBBT) combined with ascending uterine artery ligation (AUAL) in the treatment of postpartum hemorrhage (PPH) due to uterine inertia after cesarean section. METHODS: A total of 92 patients with PPH due to uterine inertia after cesarean section were divided into a study group (n=46) and a control group (n=46) in accordance with the random number table. The control group was treated with IBBT alone, while the study group was treated with IBBT combined with AUAL. The clinical efficacies, hemorrhage, surgical duration, hospital stay, hemorrhage rate after removal of tamponade, recurrence rate of PPH, changes in coagulation function and quality of life were compared between the two groups. RESULTS: The overall response rate (ORR) in the study group was 95.65%, remarkably higher than that of 80.43% in the control group (P < 0.05). The study group had a lesser amount of hemorrhage at 2 h and 24 h after surgery, a longer surgical duration, a shorter hospital stay, and lower hemorrhage rate after removal of tamponade and recurrence rate of PPH than the control group (P < 0.05). After treatment, prothrombin time, activated partial thromboplastin time and fibrinogen in the study group were markedly higher than those in the control group (P < 0.05). Compared with those before treatment, the scores of quality of life in the two groups were elevated at 3 months after treatment (P < 0.05), and the scores of quality of life in the study group were higher than those in the control group at 3 months after treatment (P < 0.05). CONCLUSION: IBBT combined with AUAL can effectively alleviate hemorrhage and improve coagulation function and quality of life of patients with PPH due to uterine inertia after cesarean section, exhibiting a definite efficacy and a high safety profile.

Planning priority conservation areas for biodiversity under climate change in topographically complex areas: A case study in Sichuan province, China.

Identifying priority conservation areas plays a significant role in conserving biodiversity under climate change, but uncertainties create challenges for conservation planning. To reduce uncertainties in the conservation planning framework, we developed an adaptation index to assess the effect of topographic complexity on species adaptation to climate change, which was incorporated into the conservation framework as conservation costs. Meanwhile, the species distributions were predicted by the Maxent model, and the priority conservation areas were optimized during different periods in Sichuan province by the Marxan model. Our results showed that the effect of topographic complexity was critical for species adaptation, but the adaptation index decreased with the temperature increase. Based on the conservation targets and costs, the distributions of priority conservation areas were mainly concentrated in mountainous areas around the Sichuan Basin where may be robust to the adaptation to climate change. In the future, the distributions of priority conservation areas had no evident changes, accounting for about 26% and 28% of the study areas. Moreover, most species habitats could be conserved in terms of conservation targets in these priority conservation areas. Therefore, our approach could achieve biodiversity conservation goals and be highly practical. More importantly, quantifying the effect of topography also is critical for options for planning conservation areas in response to climate change.

Identification of CDCA8, DSN1 and BIRC5 in Regulating Cell Cycle and Apoptosis in Osteosarcoma Using Bioinformatics and Cell Biology.

INTRODUCTION: Osteosarcoma is the most common primary tumor of bone, although some molecular markers have been identified, the detailed molecular mechanisms underlying osteosarcoma are currently not fully understood. In the present study, we attempted to identify the potential key genes and pathways in osteosarcoma using bioinformatics analysis. METHODS: GSE14359 was downloaded from the GEO database, and analyzed using Limma package. Gene Ontology and pathway enrichment analyses of the DEGs were performed in the DAVID database, followed by the construction of a protein-protein interaction (PPI) network with software Cytoscape, subnetwork modules were subsequently identified and analyzed, and further validation in human osteosarcoma tissues and osteosarcoma cells line was performed. RESULTS: 964 Differentially expressed genes (DEGs) identified, of which 222 were up-regulated and 742 were down-regulated. Among them, 10 genes (including BIRC5, MAD2L1, Bub1, DSN1, SPC24, CDCA8, STAG2, CENPA, MLF1IP and Mis12) were identified as hub genes and they were mainly enriched in pathways, including mRNA surveillance, RNA transport and PI3K-Akt signaling pathways. Further validation indicated 6 gene (DSN1, BIRC5, CDCA8, MLF1IP, MAD2L1 and SPC24) is highly expressed in osteosarcoma tissues. Among them, CDCA8, DSN1 and BIRC5 significantly promoted the proliferation of osteosarcoma cells in vitro. In terms of mechanism, DSN1 and CDCA8 were mainly involved in cell cycle regulation, while BIRC5 was mainly involved in the regulation of apoptosis pathway. CONCLUSIONS: We identified some key genes and pathways in osteosarcoma, which might be used as molecular targets or diagnostic biomarker for the diagnosis and therapy of osteosarcoma.

Research on Focal Length Measurement Scheme of Self-Collimating Optical Instrument Based on Double Grating.

In this paper, we propose a scheme for measuring the focal length of a collimating optical instrument. First, a mathematical model for measuring the focal length of a collimator with double gratings is derived based on the moiré fringe formula and the principles of geometric optics. Mathematical simulation shows that a slight difference in the focal length of two collimators has an important influence on the imaging law of moiré fringes. Our solution has a good resolution ability for focal length differences within 5‱, especially in the small angle range below 4°. Thus, the focal length of collimators can be measured by the amplification of the slight difference. Further, owing to the relative reference measurement, the measurement resolution at the symmetrical position of focal length is poor. Then, in the designed experiment, a corresponding moiré image at different angles is acquired using collimators with known focal length. The experimental results indicate that the root mean square error (RMSE) of the collimator corresponding to grating angles of 2°-4° is better than 4.7‱, indicating an ideal measurement accuracy of the proposed scheme. This work demonstrates that our proposed scheme can achieve an ideal accuracy in the measurement of a symmetrical optical path.

Chronic sciatic nerve compression induces fibrosis in dorsal root ganglia.

In the present study, pathological alterations in neurons of the dorsal root ganglia (DRG) were investigated in a rat model of chronic sciatic nerve compression. The rat model of chronic sciatic nerve compression was established by placing a 1 cm Silastic tube around the right sciatic nerve. Histological examination was performed via Masson's trichrome staining. DRG injury was assessed using Fluoro Ruby (FR) or Fluoro Gold (FG). The expression levels of target genes were examined using reverse transcription­quantitative polymerase chain reaction, western blot and immunohistochemical analyses. At 3 weeks post­compression, collagen fiber accumulation was observed in the ipsilateral area and, at 8 weeks, excessive collagen formation with muscle atrophy was observed. The collagen volume fraction gradually and significantly increased following sciatic nerve compression. In the model rats, the numbers of FR­labeled DRG neurons were significantly higher, relative to the sham­operated group, however, the numbers of FG­labeled neurons were similar. In the ipsilateral DRG neurons of the model group, the levels of transforming growth factor­ß1 (TGF­ß1) and connective tissue growth factor (CTGF) were elevated and, surrounding the neurons, the levels of collagen type I were increased, compared with those in the contralateral DRG. In the ipsilateral DRG, chronic nerve compression was associated with significantly higher levels of phosphorylated (p)­extracellular signal­regulated kinase 1/2, and significantly lower levels of p­c­Jun N­terminal kinase and p­p38, compared with those in the contralateral DRGs. Chronic sciatic nerve compression likely induced DRG pathology by upregulating the expression levels of TGF­ß1, CTGF and collagen type I, with involvement of the mitogen­activated protein kinase signaling pathway.

De novo assembly and characterization of the global transcriptome for Rhyacionia leptotubula using Illumina paired-end sequencing.

BACKGROUND: The pine tip moth, Rhyacionia leptotubula (Lepidoptera: Tortricidae) is one of the most destructive forestry pests in Yunnan Province, China. Despite its importance, less is known regarding all aspects of this pest. Understanding the genetic information of it is essential for exploring the specific traits at the molecular level. Thus, we here sequenced the transcriptome of R. leptotubula with high-throughput Illumina sequencing. METHODOLOGY/PRINCIPAL FINDINGS: In a single run, more than 60 million sequencing reads were generated. De novo assembling was performed to generate a collection of 46,910 unigenes with mean length of 642 bp. Based on Blastx search with an E-value cut-off of 10(-5), 22,581 unigenes showed significant similarities to known proteins from National Center for Biotechnology Information (NCBI) non-redundant (Nr) protein database. Of these annotated unigenes, 10,360, 6,937 and 13,894 were assigned to Gene Ontology (GO), Clusters of Orthologous Group (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively. A total of 5,926 unigenes were annotated with domain similarity derived functional information, of which 55 and 39 unigenes respectively encoding the insecticide resistance related enzymes, cytochrome P450 and carboxylesterase. Using the transcriptome data, 47 unigenes belonging to the typical "stress" genes of heat shock protein (Hsp) family were retrieved. Furthermore, 1,450 simple sequence repeats (SSRs) were detected; 3.09% of the unigenes contained SSRs. Large numbers of SSR primer pairs were designed and out of randomly verified primer pairs 80% were successfully yielded amplicons. CONCLUSIONS/SIGNIFICANCE: A large of putative R. leptotubula transcript sequences has been obtained from the deep sequencing, which extensively increases the comprehensive and integrated genomic resources of this pest. This large-scale transcriptome dataset will be an important information platform for promoting our investigation of the molecular mechanisms from various aspects in this species.

[Chemical constituents of Pileostegia viburnoides var. glabrescens].

OBJECTIVE: To study the chemical constituents of Pileostegia viburnoides var. glabrescens. METHODS: The compounds were isolated and purified by various techniques. Their structures were determined by physicochemical properties and spectral analysis. RESULTS: Five compounds were isolated and identified as friedelin (1), beta-sitosterol (2), umbelliferone (3), daucosterol (4) and skimmin (5). CONCLUSION: All the compounds were isolated from this genus for the first time.

[Study on chemical constituents of volatile oil from rhizomes and leaves of Pileostegia viburnoides var. glabrescens by GC-MS].

OBJECTIVE: To analyze the chemical constituents of volatile oil from the rhizomes and leaves of Pileostegia viburnoides var. glabrescens by GC-MS. METHODS: The volatile oil was extracted from the rhizomes and leaves of Pileostegia viburnoides var. glabrescens by steam distillation. The constituents of volatile oil were identified by GC-MS technology. RESULTS: 37 compounds were identified from the oil of rhizomes. 36 compounds were identified from the oil of leaves. The rhizomes and leaves volatile oil had 18 compounds in common. CONCLUSION: This study is the first one to report the volatile components of Pileostegia viburnoides var. glabrescens. It can provide a scientific basis for rational use of the rhizomes and leaves of Pileostegia viburnoides var. glabrescens.

Mitochondrial genome of the pine tip moth Rhyacionia leptotubula (Lepidoptera: Tortricidae).

The complete nucleotide sequence of the mitochondrial genome of the pine tip moth Rhyacionia leptotubula (Lepidoptera, Tortricidae) was determined. The entire genome is 15,877 bp in length, encoding the standard set of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and an A+T-rich control region. The gene order is typical of Lepidoptera and differs from the insect ancestral type in the location of trnM. All protein-coding sequences start with a typical ATN codon, with the exception of COI, which begins with CGA. All tRNA genes could be folded into the typical cloverleaf secondary structure, except trnS2 lacking of dihydrouridine arm. Additionally, the 7-bp long ATACTAA motif is present in the intergenic space sequence located between trnS1 and nad1, and a long T-stretch with conserved ATAGA motif exists in the A+T-rich region, as found in Lepidoptera. The mitogenome given here provides important molecular information to phylogenetic and population genetic researches.