Half-Integer Conductance Plateau at the ν=2/3 Fractional Quantum Hall State in a Quantum Point Contact.

The ν=2/3 fractional quantum Hall state is the hole-conjugate state to the primary Laughlin ν=1/3 state. We investigate transmission of edge states through quantum point contacts fabricated on a GaAs/AlGaAs heterostructure designed to have a sharp confining potential. When a small but finite bias is applied, we observe an intermediate conductance plateau with G=0.5(e^{2}/h). This plateau is observed in multiple QPCs, and persists over a significant range of magnetic field, gate voltage, and source-drain bias, making it a robust feature. Using a simple model that considers scattering and equilibration between counterflowing charged edge modes, we find this half-integer quantized plateau to be consistent with full reflection of an inner counterpropagating -1/3 edge mode while the outer integer mode is fully transmitted. In a QPC fabricated on a different heterostructure which has a softer confining potential, we instead observe an intermediate conductance plateau at G=(1/3)(e^{2}/h). These results provide support for a model at ν=2/3 in which the edge transitions from a structure having an inner upstream -1/3 charge mode and outer downstream integer mode to a structure with two downstream 1/3 charge modes when the confining potential is tuned from sharp to soft and disorder prevails.

Efficient Spin-to-Charge Conversion via Altermagnetic Spin Splitting Effect in Antiferromagnet RuO_{2}.

The relativistic spin Hall effect and inverse spin Hall effect enable the efficient generation and detection of spin current. Recently, a nonrelativistic altermagnetic spin splitting effect (ASSE) has been theoretically and experimentally reported to generate time-reversal-odd spin current with controllable spin polarization in antiferromagnet RuO_{2}. The inverse effect, electrical detection of spin current via ASSE, still remains elusive. Here we show the spin-to-charge conversion stemming from ASSE in RuO_{2} by the spin Seebeck effect measurements. Unconventionally, the spin Seebeck voltage can be detected even when the injected spin current is polarized along the directions of either the voltage channel or the thermal gradient, indicating the successful conversion of x- and z-spin polarizations into the charge current. The crystal axes-dependent conversion efficiency further demonstrates that the nontrivial spin-to-charge conversion in RuO_{2} is ascribed to ASSE, which is distinct from the magnetic or antiferromagnetic inverse spin Hall effects. Our finding not only advances the emerging research landscape of altermagnetism, but also provides a promising pathway for the spin detection.

MicroRNA-137 inhibits pituitary prolactinoma proliferation by targeting AKT2.

PURPOSE: Prolactinoma is the most common type of pituitary adenoma. Most prolactinoma need medical treatment, but some of them are aggressive and require surgery. In previous decades, some miRNAs have been manifested as oncogenes or tumor suppressors. Consequently, miRNAs' abnormal expression involves tumorigenesis, invasion, and metastasis of different types of tumors, including pituitary tumors. The current study aim to explore the aggressiveness-associated miRNAs in prolactinoma and underlying molecular mechanisms based on the bioinformatic analysis and fundamental experiment studies. METHODS: GSE46294 miRNA expression profile from the Gene Expression Omnibus (GEO) database was downloaded. Differentially expressed miRNAs (DEMs) were filtered from this data. Subsequently, the target genes of downregulated miRNAs were analyzed by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. RT-qPCR, western blot, and CCK-8 assays were used to validate the effect of miR-137 on the proliferation of MMQ cells through AKT2. Finally, the binding site of rat miR-137 to AKT2 were predicted by Targetscan and Bibiserv database, and verified by double luciferase reporter assay. RESULTS: Twenty-four changed DEMs (fourteen upregulated and ten downregulated) were identified. Target genes of downregulated DEMs were classified into three groups by GO terms. KEGG pathway enrichment analysis revealed these target genes enriched in the PI3K-Akt pathway. We also confirmed that miR-137 can target AKT2 and inhibit the proliferation of MMQ cells induced by AKT2. CONCLUSION: MiR-137 suppressed prolactinomas' aggressive behavior by targeting AKT2.

A comparison of results from antihuman globulin-graded reactions with the monocyte monolayer assay.

Blood transfusions are a common medical treatment. Risks arise when compatible blood is not available. This study assesses the correlation between antibody reaction strength at the antihuman globulin (AHG) phase of testing and the antibody clinical significance as predicted using the monocyte monolayer assay (MMA). Multiple examples of anti-K donor plasma samples were selected to sensitize K+k+ red blood cells (RBCs). Reactivity was confirmed by testing the sensitized K+k+ RBCs at saline-AHG. Antibody titers were determined by serial dilution using neat plasma. Sixteen samples were selected for the study based on comparable graded reactions with neat plasma (1+, 2+, 3+, and 4+) and similar titration endpoints. Each sample was used to sensitize the same Kk donor and then tested by monocytes to evaluate the clinical significance using the MMA, an in vitro procedure that mimics in vivo extravascular hemolysis to predict the survivability of incompatible transfused RBCs. The monocyte index (MI), i.e., the percentage of RBCs adhered, ingested, or both versus free monocytes, was calculated for each sample. Regardless of the reaction strength, all examples of anti-K were predicted to be clinically significant. While anti-K is known to be clinically significant, the immunogenicity rate of K ensures ample supply of antibody samples for inclusion in this project. This study demonstrates that in vitro antibody strength is highly subjective and variable. These results show no correlation between graded reaction strength at AHG and the predicted clinical significance of an antibody as assessed using the MMA.

A 2-bp deletion in intron 1 of TMEM182 is associated with TMEM182 mRNA expression and chicken body weight.

1. Searching for molecular markers related to growth and carcase traits plays a critical role in improvement of the production performance of broilers. Previous studies found that transmembrane protein 182 (TMEM182) inhibits skeletal muscle development, growth, and regeneration, implying that the TMEM182 gene plays an important role during the development process of skeletal muscle.2. A novel 2-bp indel in intron 1 of TMEM182 was detected in a yellow chicken population derived from the cross of White Recessive Rock chickens with Xinghua chickens, and three genotypes II (inserted homozygote), ID (inserted and deleted heterozygote) and DD (deleted homozygote) were observed. Association analyses indicated that the indel was significantly associated with the body weight, muscle fibre area, breast muscle weight and wing weight in the F2 population.3. The expression of TMEM182 in leg muscle of chickens with II genotype was higher than that with DD genotype, with the 2-bp indel located in one of the putative PAX4 binding sites. Further research through luciferase assays revealed that the PAX4 could bind to the putative binding site and increase the TMEM182 transcription, with the 2-bp deletion disrupting the binding of PAX4.4. The present study provides evidence for the association of the novel 2-bp indel in intron 1 of TMEM182 with the growth and carcase traits of chickens. This 2-bp indel could be used as a genetic marker in broiler breeding.

[Outcome analysis of pregnancy termination and expectant treatment in pregnant women with suspected invasive placenta accreta spectrum disorders in the second trimester].

Objective: To investigate the maternal and fetal outcomes of expectant treatment and early termination of pregnancy in pregnant women with suspected invasive placenta accreta spectrum disorders (PAS) in the second trimester. Methods: A retrospective cohort study was performed on 51 pregnant women with suspected invasive PAS (ultrasound score ≥10) evaluated by ultrasound with gestational age <26 weeks and confirmed as invasive PAS by intraoperative findings or postoperative pathology in Peking University Third Hospital from January 2015 to January 2022. According to the informed choice of pregnant women and their families, they were divided into expectant treatment group (37 cases) and mid-term termination group (14 cases). The general clinical data and outcome indexes of the two groups were analyzed by χ2 test, Mann-Whitney U rank sum test, logistic regression and linear regression. Results: (1) General clinical data: among 51 pregnant women who were assessed as suspected invasive PAS by ultrasonography in the second trimester, invasive PAS was finally diagnosed by intraoperative findings and postoperative pathology, among which 46 cases (90%) were placenta percreta and 5 cases (10%) were placenta increta. (2) Outcome indicators: univariate analysis showed that there were no statistically significant differences in the intraoperative blood loss (median: 2 200 vs 2 150 ml), the proportion of blood loss >1 500 ml [73% (27/37) vs 9/14], the hysterectomy rate [62% (23/37) vs 8/14], the rate of intensive care unit (ICU) admission [78% (29/37) vs 9/14] between the expectant treatment group and the mid-term termination group (all P>0.05). Multivariate analysis showed that the rate of intraoperative blood loss >1 500 ml (aOR=0.481, 95%CI: 0.017-13.958; P=0.670), hysterectomy (aOR=0.264, 95%CI: 0.011-6.569, P=0.417) and ICU admission (aOR=1.327, 95%CI: 0.048-36.882, P=0.867) between the two groups showed no statistical differences. (3) Outcome analysis: all 37 cases in the expectant treatment group had live births and no early neonatal death. Five pregnant women (14%, 5/37) in the expectant treatment group underwent emergency cesarean section in the course of expectant treatment. In the mid-term termination group, all pregnancies were terminated by operation, including 9 cases of hysterectomy and 5 cases of placental hysterectomy. There was 1 fetal survival (gestational age of termination: 27+4 weeks) and 13 fetal death in the mid-term termination group. Conclusions: Pregnant women who are diagnosed as suspected invasive PAS, especially those with placenta percreta, have the risk of uterine rupture and emergency surgery in the course of expectant treatment. However, early termination of pregnancy does not reduce the risk of intraoperative blood loss and hysterectomy.

Mucin 5AC is significantly upregulated in exosomes from the nasal lavage fluid and may promote the expression of COX-2, VEGF and MMP-9: an implication in nasal polyp pathogenesis.

BACKGROUND: Exosomes are critical mediators of intercellular communication and could be involved in many human diseases; however, little is known about the role of exosomes in nasal polyps (NP). METHODS: Exosomes in nasal lavage fluids (NLF) were isolated by ultracentrifugation. Exosome identity was validated by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and specific exosomal markers. The exosome proteome was revealed by LC-MS/MS, and the expression of the candidate exosomal protein, mucin 5AC, was confirmed by Western blot analysis and immunohistochemistry (IHC). Cellular uptake of the exosomes was monitored by fluorescence confocal microscopy and the ensuing effects on COX-2, VEGF and MMP-2/MMP-9 were determined by Western blotting, ELISA and gelatin zymography, respectively. RESULTS: Mass spectrometry analysis and subsequent verification by Western blotting identified that mucin 5AC was significantly upregulated in exosomes from NLFs of NP patients. Moreover, the expression of mucin 5AC was increased in the tissue specimens of the NP patients. Functional assays suggest that the mucin 5 AC-enriched exosomes could be effectively taken up by chronic rhinosinusitis without NP (CRSsNP)-derived fibroblasts, the control cells, resulting in a significant increase in the expression of COX-2, VEGF and MMP-9. CONCLUSIONS: Mucin 5AC, the major airway mucin, cannot only be carried and transferred by nasal exosomes, but may also promote tissue remodeling and angiogenesis and thus could be a potential therapeutic target of NP.

[Long-term mesh-related complications after total pelvic reconstruction surgery with tension-free transvaginal mesh].

Objective: To investigate the long-term mesh-related complications and treatment outcome of total pelvic reconstruction surgery with tension-free transvaginal mesh (PROSIMATM pelvic floor repair system). Methods: From July 2010 to June 2012, 48 patients with severe pelvic organ prolapse(POP)who underwent PROSIMATM were enrolled and treated in Peking Union Medical College Hospital. 29 patients (60.4%) were followed up periodically for at least 3 years to observe the occurrence of long-term mesh-related complications, and the clinical characteristics, classification of complications and treatment outcome of these cases were summarized. Results: The 29 cases with an average age of (65.1±5.2) years were followed up for an average of (71.6±21.2) months. The last follow-up was 36-105 months after treatment. The long-term success rate of the treatment was 79.3% (n=23). There were 18 cases of mesh exposure (18/48, 37.5%), of which 10 cases (55.6%) were new and persistent. 4 cases (4/18) had symptoms; the rest were found by pelvic examination. Ten patients (10/18) were positive for vaginal swab culture. As for treatment outcome, one case suffered from mesh erosion into the bladder. 4 patients (6.9%) complained of postoperative pain. Twenty-nine patients were divided into the exposure group (n=18) and the non-exposure group (n=11) according to mesh exposure occurrence. There was a significant difference in the proportion of positive swab culture results between the two groups (P=0.019), but no significant difference in the incidence of postoperative pain (P=0.566). Conclusion: The incidence of long-term mesh exposure in PROSIMATM is not low, and most of patients with which had no symptoms.

[Three-dimensional MRI reconstruction research on the anatomical relationship among uterosacral ligament and ureter or rectum in pelvic organ prolapse patients].

Objective: To study the anatomical relationship among uterosacral ligament and ureter or rectum by using MRI three-dimensional reconstruction model in pelvic organ prolapse (POP) patients. Methods: According to the research standard, 67 POP patients were enrolled, who accepted pelvic MRI before surgery in Nanfang Hospital, Southern Medical University during May 2015 to March 2020. Three-dimensional model of uterosacral ligament was reconstructed. The intersection point of the fitting curve of uterosacral ligament and ischial spine level marked point P0, every 1 cm increasing from P0 towards the sacrum marked points P1, P2, and P3. Distances were measured between rectum or ureter to uterosacral ligament respectively at the P0-P3 horizontal levels. Results: (1) The distances between the left ureter and the left uterosacral ligament were (15.45±7.46) to (19.31±11.38) mm, and the distances between the right ureter and the right uterosacral ligament were (13.77±8.16) to (14.78±9.18) mm. At the P1 horizontal level ureters were the closest to uterosacral ligaments, and the right ureter was the closest to right uterosacral ligament [(13.45±9.34) mm] at P2 horizontal level in severe POP group. The farthest distance presented at the P3 horizontal level between bilateral ureters and uterosacral ligaments. (2) At the P0 horizontal level, the rectum was the closest to the bilateral uterosacral ligaments [left: (20.62±9.99) mm, right: (16.82±9.63) mm; P=0.026], and the rectum was closer to the right uterosacral ligament. There were no significant differences in the distance between rectum and bilateral uterosacral ligaments in mild POP group (P>0.05), and the results of severe POP group also showed the rectum was closer to the right uterosacral ligament [(15.64±10.31) mm at P0 horizontal level]. Conclusions: Right ureter and rectum are closer to the right uterosacral ligament. Gynecologists should pay more attention to avoid damaging the right ureter and rectum during the operation of the right uterosacral ligament in POP patients.

Genuine tripartite Einstein-Podolsky-Rosen steering in the cascaded nonlinear processes of third-harmonic generation.

Recently, Einstein-Podolski-Rosen (EPR) steering has important application in quantum information processing, and it has been received considerable attention because of its uniqueness. The properties of quantum steering among three output fields generated by cascaded nonlinear processes of quasi-phase-matching third-harmonic generation in an optical cavity are investigated. Based on the criteria for multipartite EPR steering which proposed by He and Reid [PRL, 111, 250403 (2013)], the genuine tripartite EPR steering among pump, second-harmonic, and third-harmonic is demonstrated. The parameters which affect the quantum property are also discussed.

Genome-wide analysis reveals genetic diversity, linkage disequilibrium, and selection for milk production traits in Chinese buffalo breeds.

The water buffalo is an important dual-purpose livestock that is widespread throughout central and southern China. However, there has been no characterization of the population genetics of Chinese buffalo. Using an Axiom buffalo genotyping array (Thermo Fisher Scientific, Wilmington, DE), we analyzed the genetic diversity, linkage disequilibrium pattern, and signature of selection in 176 Chinese buffaloes from 13 breeds. A total of 35,547 SNP passed quality control and were used for further analyses. Population genetic analysis revealed a clear separation between swamp and river types. Ten Chinese indigenous breeds were clustered into the swamp group, the Murrah and Nili-Ravi breeds were clustered into the river group, and the crossbred breed was closer to the river group. Genetic diversity analysis showed that the swamp group had a lower average expected heterozygosity. Linkage disequilibrium decay distance was much shorter in the swamp group compared with the river group, with an average square of correlation coefficient value of 0.2 of approximately 50 kb. Analysis of runs of homozygosity indicated extensive remote and recent inbreeding within swamp and river groups, respectively. Moreover, one genomic region under selection was detected between the river and swamp groups. Our findings contribute to our understanding of the characterization of population genetics in Chinese buffaloes, which in turn may be used in buffalo breeding programs.

[Clinical characteristics and related factors of acute tubular necrosis in patients with minimal change disease].

Objective: To investigate the clinical characteristics and related factors of acute tubular necrosis (ATN) in patients with minimal change disease (MCD). Methods: Patients from Chinese PLA General Hospital who were pathologically diagnosed with MCD and had clinical manifestations of nephrotic syndrome from January 1, 2013 to December 31, 2019 were included. The clinical and pathological data of patients were retrospectively analyzed. Meanwhile, the incidence and clinical characteristics of ATN in different age groups were compared. The risk factors for ATN were assessed using binary logistic regression. Results: A total of 525 patients were included, with a gender ratio of 1.56∶1 (male: female), aged 33 (21, 48) years old. ATN occurred in 49 (9.3%) of 525 patients, of which 34 were male and 15 were female. The incidence of ATN increased with age in MCD patients of different age groups (χ(2)=31.442, P<0.001). The incidence of ATN in groups of age≤20 years, 21-40 years, 41-60 years, and >60 years was 2.4% (3/123), 5.2% (10/192), 13.2% (20/152) and 27.6% (16/58), respectively. Elevations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT) and serum IgE occurred in 92 patients (17.5%), 53 patients (10.1%), 99 patients (18.9%), and 303 patients (57.7%), respectively. There were significant differences in age, ALT, serum creatinine, serum urea nitrogen, history of diabetes and history of hypertension between non-ATN group and ATN group (all P<0.05). The results of logistic regression analysis showed that>40 years old (OR=6.283, 95% CI: 2.695-14.649, P<0.001) and serum albumin (OR=0.924, 95% CI: 0.857-0.997, P=0.040) was independently associated with ATN in MCD patients. Conclusion: Age>40 years is an independent risk factor and serum albumin is a protective factor for ATN in MCD patients.

Association of P2X7R gene with serum lipid profiles in Chinese postmenopausal women with osteoporosis.

Objectives: The aim was to study the relationship between purinergic P2X7 receptor (P2X7R) functional genetic polymorphisms and lipid profiles in Chinese postmenopausal osteoporosis (OP) patients and controls. Methods: A total of 517 OP patients and 531 controls were randomly recruited by cluster sampling; blood was drawn to analyze P2X7R genetic polymorphisms and serum lipid levels. Bone mineral density (BMD) at the lumbar spine and hip was measured via dual-energy X-ray absorptiometry. Results:P2X7R rs2230911 was found to be associated with serum total cholesterol, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein, and BMD at the lumbar spine and hip in OP patients (p < 0.05). P2X7R rs3751143 was shown to be associated with serum TG and hip BMD in OP patients (p < 0.05). Furthermore, their estimated haplotype (rs1718119G-rs2230911C-rs3751143A) was indicated to be associated with TG, HDL, and BMD at the lumbar spine and hip in OP patients. However, no difference in the level of lipid profiles or BMD was found to be related to P2X7R genotype or haplotype in the control group (p>0.05). Conclusions: Our findings suggest that P2X7R functional genetic polymorphisms and their estimated haplotypes are associated with serum lipid concentrations and BMD among Chinese postmenopausal women with OP.

Regulation of geminin by neuropeptide Y in vascular smooth muscle cell proliferation : A current review.

Geminin, a key regulator of DNA replication licensing in the cell cycle, plays an essential role in determining the fate of cells via suppression of cell proliferation and cellular differentiation. Neuropeptide Y (NPY) intensifies the proliferation of vascular smooth muscle cells (VSMCs) directly by binding with Y1 receptors. In vitro experiments have shown that stimulation of NPY on VSMCs via regulation of geminin is a double-edged sword. Given that the proliferation and the phenotypic transformation of VSMCs increase the risk for progression of atherosclerosis, we focus on the role of geminin interference in determining the fate of VSMCs. Furthermore, we discuss the therapeutic potential of peripheral neurotransmitter interference, thus pointing toward future research directions in the treatment of atherosclerosis.

Effect of N-acetyl-l-methionine supplementation on lactation performance and plasma variables in mid-lactating dairy cows.

The objective of current study was to investigate the effect of N-acetyl-l-methionine (NALM) supplementation on lactation performance and plasma variables in mid-lactating dairy cows. Forty-eight multiparous cows were blocked into 12 groups based on parity, days in milk, and milk production and were randomly assigned to 1 of the 4 treatments: 0, 15, 30, or 60 g/d of NALM per cow to supplement the basal diet. The experiment was conducted over a 13-wk period, with the first week as adaptation. The yields of milk, fat-corrected milk, and milk lactose were increased quadratically, and energy-corrected milk yield tended to increase with increased NALM supplementation in a quadratic manner. The dry matter intake, milk protein yield, milk fat yield, contents of milk composition (protein, fat, lactose, total solids, and milk urea nitrogen), feed efficiency, and body weight change were not affected by NALM supplementation. In addition, plasma methionine concentration was increased quadratically, and proline, total nonessential AA, and total AA concentrations were significantly higher in the 30 g/d group compared with that of the control group. However, other AA and total essential AA concentrations were not affected with supplementation of NALM. Adding NALM increased concentrations of total protein and globulin in plasma, but decreased plasma urea nitrogen concentration in a quadratic manner. Meanwhile, plasma malonaldehyde concentration decreased linearly as doses of NALM addition increased. Our results suggested that the supplementation of NALM improved milk yield and protein synthesis in the liver, and lowered lipid peroxidation in mid-lactating dairy cows.

[Genetic analysis and prenatal diagnosis of Duchenne or Becker muscular dystrophy].

Objective: To explore the mutation characteristics of DMD gene in patients with Duchenne or Becker muscular dystrophy and female carriers, to provide effective prenatal diagnosis. Methods: Samples were collected from 94 male patients clinically diagnosed with Duchenne or Becker muscular dystrophy and 121 corresponding female relatives from Qingdao Women and Children's Hospital from June 2011 to October 2018. Multiplex ligation-dependent probe amplification (MLPA) was used to detect their DMD gene, and 23 high risk pregnants were performed prenatal diagnosis. Any candidate of DMD gene single-exon deletion was validated by further PCR amplification. The sample with whole DMD gene deletion was confirmed by chromosomal microarray analysis (CMA) to detect copy number variations and break site. Results: Among 94 clinical Duchenne or Becker muscular dystrophy patients, 66(70.2%, 66/94) were detected gene mutation; 56 cases were exon deletion mutation and 10 cases were duplication mutation. In 121 female relatives, 48 cases (39.7%, 48/121) were diagnosed as carriers. The mutation carrying rate, was 64.5% (40/62) identified in 62 mothers of Duchenne or Becker muscular dystrophy patients. Five Duchenne or Becker muscular dystrophy fetuses and 5 carrier fetuses were prenatally diagnosed in 23 high risk pregnants. Two children with the entire DMD gene deletion were identified more deletions at Xp21, with deletions of 6.66 Mb and 10.64 Mb respectively. Conclusions: MLPA may be an important method to detect DMD gene mutation of deletion and duplication. Therefore, the diagnosis of probands, female carriers and making an effective prenatal diagnosis are essential to reduce the birth of children with Duchenne or Becker muscular dystrophy.

[An analysis on incidence of HIV-1 epidemics among men who have sex with men in Sichuan Province during 2011-2015].

The assay was used in HIV/AIDS surveillance sentinel sites to identify recent HIV-1 infection, to estimate HIV-1 incidence and understand the epidemic trends among men who have sex with men during 2011-2015. During 2011-2015, the HIV-1 incidence of men who have sex with men was 5.16%(95%CI: 4.65%-5.66%) in Sichuan Province. According to, a total of 9 cities had been divided into two type of regions: the first type(the proportion of live HIV/AIDS accounts for more than 0.1% of the permanent population, and the number of live HIV/AIDS has reached 500 cases and above) and the second type(the proportion of live HIV/AIDS accounts for 0.03% to 0.100% of the permanent population, and the number of live HIV/AIDS has reached 100-500 cases). During 2011-2015, the HIV-1 incidence of the second type was 4.24% (95%CI: 3.72%-4.76%). The HIV-1 incidence of men who have sex with men was at a high level. The spread of HIV-1 to the second region was possible.

Efficient Fusion at Neutral pH by Human Immunodeficiency Virus gp41 Trimers Containing the Fusion Peptide and Transmembrane Domains.

Human immunodeficiency virus (HIV) is membrane-enveloped, and an initial infection step is joining/fusion of viral and cell membranes. This step is catalyzed by gp41, which is a single-pass integral viral membrane protein. The protein contains an ∼170-residue ectodomain located outside the virus that is important for fusion and includes the fusion peptide (FP), N-helix, loop, C-helix, and viral membrane-proximal external region (MPER). The virion initially has noncovalent complexes between three gp41 ectodomains and three gp120 proteins. A gp120 contains ∼500 residues and functions to identify target T-cells and macrophages via binding to specific protein receptors of the target cell membrane. gp120 moves away from the gp41 ectodomain, and the ectodomain is thought to bind to the target cell membrane and mediate membrane fusion. The secondary and tertiary structures of the ectodomain are different in the initial complex with gp120 and the final state without gp120. There is not yet imaging of gp41 during fusion, so the temporal relationship between the gp41 and membrane structures is not known. This study describes biophysical and functional characterization of large gp41 constructs that include the ectodomain and transmembrane domain (TM). Significant fusion is observed of both neutral and anionic vesicles at neutral pH, which reflects the expected conditions of HIV/cell fusion. Fusion is enhanced by the FP, which in HIV/cell fusion likely contacts the host membrane, and the MPER and TM, which respectively interfacially contact and traverse the HIV membrane. Initial contact with vesicles is made by protein trimers that are in a native oligomeric state that reflects the initial complex with gp120 and also is commonly observed for the ectodomain without gp120. Circular dichroism data support helical structure for the N-helix, C-helix, and MPER and nonhelical structure for the FP and loop. Distributions of monomer, trimer, and hexamer states are observed by size-exclusion chromatography (SEC), with dependences on solubilizing detergent and construct. These SEC and other data are integrated into a refined working model of HIV/cell fusion that includes dissociation of the ectodomain into gp41 monomers followed by folding into hairpins that appose the two membranes, and subsequent fusion catalysis by trimers and hexamers of hairpins. The monomer and oligomer gp41 states may therefore satisfy dual requirements for HIV entry of membrane apposition and fusion.

Predictors for unsuccessful pessary fitting in women with symptomatic pelvic organ prolapse: a prospective study.

OBJECTIVE: To evaluate the success rate of vaginal pessary fitting and identify the risk factors associated with unsuccessful pessary fitting in a large cohort of patients with symptomatic pelvic organ prolapse (POP). DESIGN: Prospective observational study. SETTING: The Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Beijing, China. POPULATION: Women with symptomatic POP between May 2015 and December 2016 (n = 343). METHODS: A successful pessary fitting was defined as a patient fitted with a pessary at the initial fitting and continued use 2 weeks later. The independent samples t-test, non-parametric test, Chi-square test, Fisher's exact test, logistic regression and receiver operating characteristic curves were used for the data analysis. MAIN OUTCOME MEASURES: The success rate of vaginal pessary fitting and the risk factors associated with unsuccessful pessary fitting. RESULTS: 302 patients had successful pessary fitting (88.0% success rate). A higher body mass index [BMI; 24.7 ± 3.1 kg/m2 in the successful group versus 25.7 ± 3.8 kg/m2 in the unsuccessful group, odds ratio (OR) 1.174, 95% CI 1.055-1.307, P = 0.003] and a shorter TVL [8.0 (8-9) cm in the successful group versus 7.0 (6.8-8) cm in the unsuccessful group, OR 0.338, 95% CI 0.223-0.513, P < 0.001) were independent predictors of an unsuccessful pessary fitting. The receiver operating characteristic curve showed that patients with a total vaginal length (TVL) less than 7.3 cm had a higher unsuccessful pessary fitting rate (sensitivity = 0.82, specificity = 0.64). CONCLUSIONS: A higher BMI and shorter TVL were independent predictors of an unsuccessful pessary fitting. Patients with a TVL <7.3 cm are not appropriate candidates for a vaginal pessary. TWEETABLE ABSTRACT: A higher BMI and shorter TVL (<7.3 cm) were independent predictors of an unsuccessful pessary fitting.