Non-neutralizing antibodies targeting the immunogenic regions of HIV-1 envelope reduce mucosal infection and virus burden in humanized mice.

Antibodies are principal immune components elicited by vaccines to induce protection from microbial pathogens. In the Thai RV144 HIV-1 vaccine trial, vaccine efficacy was 31% and the sole primary correlate of reduced risk was shown to be vigorous antibody response targeting the V1V2 region of HIV-1 envelope. Antibodies against V3 also were inversely correlated with infection risk in subsets of vaccinees. Antibodies recognizing these regions, however, do not exhibit potent neutralizing activity. Therefore, we examined the antiviral potential of poorly neutralizing monoclonal antibodies (mAbs) against immunodominant V1V2 and V3 sites by passive administration of human mAbs to humanized mice engrafted with CD34+ hematopoietic stem cells, followed by mucosal challenge with an HIV-1 infectious molecular clone expressing the envelope of a tier 2 resistant HIV-1 strain. Treatment with anti-V1V2 mAb 2158 or anti-V3 mAb 2219 did not prevent infection, but V3 mAb 2219 displayed a superior potency compared to V1V2 mAb 2158 in reducing virus burden. While these mAbs had no or weak neutralizing activity and elicited undetectable levels of antibody-dependent cellular cytotoxicity (ADCC), V3 mAb 2219 displayed a greater capacity to bind virus- and cell-associated HIV-1 envelope and to mediate antibody-dependent cellular phagocytosis (ADCP) and C1q complement binding as compared to V1V2 mAb 2158. Mutations in the Fc region of 2219 diminished these effector activities in vitro and lessened virus control in humanized mice. These results demonstrate the importance of Fc functions other than ADCC for antibodies without potent neutralizing activity.

Acid-Promoted Multicomponent Reaction To Synthesize 4-Phosphorylated 4H-Chromenes.

An effective multicomponent reaction for the synthesis of 4-phosphorylated 4H-chromenes via a tandem phosphorylation/alkylation/cyclization/dehydration sequence with water as the only byproduct was developed. Extensive mechanistic investigations involving in situ NMR experiments, time control experiments, and in situ HRMS experiment allowed us to elucidate the order of each subreaction to arrive at a complete understanding of the underlying mechanism of this multicomponent reaction. Mechanistic data confirm that the reaction begins with a phospha-aldol-elimination, followed by addition of a ketone enolate, intermolecular alkylation, intramolecular cyclization, and dehydration under acidic conditions.

Effect of glycotoxicity and lipotoxicity on carbohydrate antigen 19 - 9 in the patients with diabetes.

OBJECTIVES: In comparison to the subjects without diabetes, a greater concentration of serum carbohydrate antigen 19 - 9 (CA 19 - 9) was observed in the subjects with diabetes. Nevertheless, since the occurrence of abnormal CA 19 - 9 is not widespread among the whole diabetic population, this phenomenon has not attracted enough attention. The prevalence of abnormal CA 19 - 9 in hospitalized patients with diabetes was the focus of our research. METHOD: A total of 385 subjects with diabetes and 200 controls were enrolled and all had been tested the CA19-9 levels. Cases of cancers were excluded through examination and followup for 1 year. RESULTS: We found that the rate of patients with abnormal CA19-9 level was 8.3%. The rate of patients with abnormal CA19-9 level was 14.0% in the HbA1c ≥ 9% group, and 3.0% in the HbA1c < 9% group, 2.5% in the control group. There was no significant difference in the HbA1c < 9% group and the control group. A significant correlation between serum CA19-9 and both HbA1c and total cholesterol was observed, yet no difference in CRP level was observed between subjects with normal CA19-9 level and subjects with abnormal CA19-9 level. However, a significant difference in fasting C-peptide levels was observed between the two groups, p = 0.039. CONCLUSION: The percentage of patients with diabetes exhibiting elevated CA19-9 level is 14% in the HbA1c ≥ 9% diabetic patients, much higher than expected. The underlying mechanism may be related to islet injury caused by glycotoxicity and lipotoxicity. STRENGTHS AND LIMITATIONS OF THE STUDY: We studied the rate of hospitalized diabetic patients with elevated CA 19 - 9 which were characterized with poorly controlled blood glucose. We found that the elevation of CA 19 - 9 was unexpectedly high in diabetic inpatients without development to cancer. The limitation of this study is that the underlying mechanism is not sufficiently studied.

Three-Component Direct Phosphorylation of Aldehydes and Alkylation of Ketones: Synthesis of γ-Ketophosphine Oxides under Acidic Conditions.

An effective and economical acid-promoted three-component reaction for the construction of C-P and C-C bonds for the synthesis of γ-ketophosphine oxides with water as the only byproduct was developed. Detailed mechanistic experiments confirmed that the reaction proceeds by phospha-aldol elimination, in which a benzylic carbocation is generated from the phosphorylation of aldehydes, which then reacts with ketone enolates under acidic conditions.

Virus Control in Vaccinated Rhesus Macaques Is Associated with Neutralizing and Capturing Antibodies against the SHIV Challenge Virus but Not with V1V2 Vaccine-Induced Anti-V2 Antibodies Alone.

The role of vaccine-induced anti-V2 Abs was tested in three protection experiments in rhesus macaques. In an experiment using immunogens similar to those in the RV144 vaccine trial (Anti-envelope [Env]), nine rhesus macaques were coimmunized with gp16092TH023 DNA and SIV gag and gp120A244 and gp120MN proteins. In two V2-focused experiments (Anti-V2 and Anti-V2 Mucosal), nine macaques in each group were immunized with V1V292TH023 DNA, V1V2A244 and V1V2CasaeA2 proteins, and cyclic V2CaseA2 peptide. DNA and protein immunogens, formulated in Adjuplex, were given at 0, 4, 12, and 20 weeks, followed by intrarectal SHIVBaL.P4 challenges. Peak plasma viral loads (PVL) of 106-107 copies/ml developed in all nine sham controls. Overall, PVL was undetectable in one third of immunized macaques, and two animals tightly controlled the virus with the Anti-V2 Mucosal vaccine strategy. In the Anti-Env study, Abs that captured or neutralized SHIVBaL.P4 inversely correlated with PVL. Conversely, no correlation with PVL was found in the Anti-V2 experiments with nonneutralizing plasma Abs that only captured virus weakly. Titers of Abs against eight V1V2 scaffolds and cyclic V2 peptides were comparable between controllers and noncontrollers as were Ab-dependent cellular cytotoxicity and Ab-dependent cell-mediated virus inhibition activities against SHIV-infected target cells and phagocytosis of gp120-coated beads. The Anti-Env experiment supports the role of vaccine-elicited neutralizing and nonneutralizing Abs in control of PVL. However, the two V2-focused experiments did not support a role for nonneutralizing V2 Abs alone in controlling PVL, as neither Ab-dependent cellular cytotoxicity, Ab-dependent cell-mediated virus inhibition, nor phagocytosis correlated inversely with heterologous SHIVBaL.P4 infection.

Effect of noninvasive embryo viability testing versus conventional IVF on the live birth rate in IVF/ICSI patients: a study protocol for a double-blind, multicenter, randomized controlled trial.

BACKGROUND: Preimplantation genetic testing for aneuploidy (PGT-A) was demonstrated to be superior to conventional IVF in reducing the incidence of miscarriage and abnormal offspring after the first embryo transfer (ET). PGT-A requires several embryo trophectoderm cells, but its negative impacts on embryo development and long-term influence on the health conditions of conceived children have always been a concern. As an alternative, noninvasive PGT-A (niPGT-A) approaches using spent blastocyst culture medium (SBCM) achieved comparable accuracy with PGT-A in several pilot studies. The main objective of this study is to determine whether noninvasive embryo viability testing (niEVT) results in better clinical outcomes than conventional IVF after the first embryo transfer. Furthermore, we further investigated whether niEVT results in higher the live birth rate between women with advanced maternal age (AMA, > 35 years old) and young women or among patients for whom different fertilization protocols are adopted. METHODS: This study will be a double-blind, multicenter, randomized controlled trial (RCT) studying patients of different ages (20-43 years) undergoing different fertilization protocols (in vitro fertilization [IVF] or intracytoplasmic sperm injection [ICSI]). We will enroll 1140 patients at eight reproductive medical centers over 24 months. Eligible patients should have at least two good-quality blastocysts (better than grade 4 CB). The primary outcome will be the live birth rate of the first embryo transfer (ET). Secondary outcomes will include the clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, cumulative live birth rate, ectopic pregnancy rate, and time to pregnancy. DISCUSSION: In this study, patients who undergo noninvasive embryo viability testing (niEVT) will be compared to women treated by conventional IVF. We will determine the effects on the pregnancy rate, miscarriage rate, and live birth rate and adverse events. We will also investigate whether there is any difference in clinical outcomes among patients with different ages and fertilization protocols (IVF/ICSI). This trial will provide clinical evidence of the effect of noninvasive embryo viability testing on the clinical outcomes of the first embryo transfer. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) Identifier: ChiCTR2100051408. 9 September 2021.

Levosimendan administration is not associated with increased risk of bleeding and blood transfusion requirement in patients undergoing off-pump coronary artery bypass grafting: a retrospective study from single center.

BACKGROUND: Levosimendan (LEVO) is a positive inotropic drug which could increase myocardial contractility and reduce the mortality rate in cardiac surgical patients. However, Whether LEVO is associated with postoperative bleeding and blood transfusion in cardiac surgical patients is controversial. Therefore, the current study was designed to investigate the impact of LEVO administration on bleeding and blood transfusion requirement in off-pump coronary artery bypass grafting (OPCAB) patients. METHODS: In a retrospective analysis, a total of 292 patients, aged 40-87 years, undergoing elective OPCAB between January 2019 and July 2019, were divided into LEVO group (n = 151) and Control group (n = 141). Patients in LEVO group continuously received LEVO at a rate of 0.1-0.2 µg kg-1 min-1 after anesthesia induction until 24 hours after OPCAB or patients in Control group received no LEVO. The primary outcome was postoperative chest drainage volume. The secondary outcomes were reoperation for postoperative bleeding, transfusion requirement of red blood cells (RBCs), fresh frozen plasma (FFP) and platelet concentrate (PC), etc. Comparisons of two groups were performed with the Student's t-test or Wilcoxon-Mann-Whitney test. RESULTS: There was no significant difference with respect to chest drainage volume ((956.29 ± 555.45) ml vs (1003.19 ± 572.25) ml, p = 0.478) and the incidence of reoperation for postoperative bleeding (1.32% vs 1.42%, p = 0.945) between LEVO group and Control group. The transfusion incidence and volume of allogeneic RBCs, FFP, and PC were comparable between two groups. CONCLUSIONS: LEVO administration was neither associated with more postoperative blood loss nor increased allogeneic blood transfusion requirement in OPCAB patients.

Thermal Behaviors and Interaction Mechanism of Ammonium Dinitramide with Nitrocellulose.

The initial interaction mechanism is very important for the design and safety of nano-scale composite energetic materials composed of ammonium dinitramide (ADN) and nitrocellulose (NC). The thermal behaviors of ADN, NC and an NC/ADN mixture under different conditions were studied by using differential scanning calorimetry (DSC) with sealed crucibles, an accelerating rate calorimeter (ARC), a self-developed gas pressure measurement instrument and a DSC-thermogravimetry (TG)-quadrupole mass spectroscopy (MS)-Fourier transform infrared spectroscopy (FTIR) combined technique. The results show that the exothermic peak temperature of the NC/ADN mixture shifted forward greatly in both open and closed circumstances compared to those of NC or ADN. After 585.5 min under quasi-adiabatic conditions, the NC/ADN mixture stepped into the self-heating stage at 106.4 °C, which was much less than the initial temperatures of NC or ADN. The significant reduction in net pressure increment of NC, ADN and the NC/ADN mixture under vacuum indicates that ADN initiated the interaction of NC with ADN. Compared to gas products of NC or ADN, two new kinds of oxidative gases O2 and HNO2 appeared for the NC/ADN mixture, while NH3 and aldehyde disappeared. The mixing of NC with ADN did not change the initial decomposition pathway of either, but NC made ADN more inclined to decompose into N2O, which resulted in the formation of oxidative gases O2 and HNO2. The thermal decomposition of ADN dominated the initial thermal decomposition stage of the NC/ADN mixture, followed by the oxidation of NC and the cation of ADN.

RNA m6A reader YTHDF1 facilitates inflammation via enhancing NLRP3 translation.

N6-methyladenosine (m6A) modification of mRNAs is involved in multiple essential biological processes, dynamically regulated by m6A "writers", "erasers", and "readers". Yet, the detailed functional roles of RNA m6A reader proteins, such as YTHDFs, are largely unknown. Herein we show that YTHDF1 promotes pro-inflammatory IL-1ß production in macrophages during bacterial infections. YTHDF1 overexpression promotes NLRP3 translation. In vivo knockdown of YTHDF1 facilitates survival in a mouse model of sepsis. Thus, YTHDF1 participates in inflammatory responses and subsequent injuries, serving as a new potential therapeutic target in clinical treatment of inflammatory diseases.

Comparison of embryo implantation potential between time-lapse incubators and standard incubators: a randomized controlled study.

RESEARCH QUESTION: What are the potential clinical benefits of embryo culture and assessment in a time-lapse incubator compared with a standard incubator using static assessment? DESIGN: This large multicentre, single-blinded, randomized controlled study included 1224 participants randomly assigned (1:1) to the time-lapse or standard incubator group. In all patients one or two embryos were transferred on day 3. The primary outcome was the implantation rate in the first embryo transfer cycle. Secondary outcomes included the cumulative implantation rate, live birth rate in the first embryo transfer cycle and cumulative live birth rate. RESULTS: Among 1224 participants recruited, 1182 underwent embryo transfer. The number of successfully implanted embryos in the first transfer cycle was significantly higher in the time-lapse incubator group (time-lapse group: 52.35%, standard incubator group: 47.11%, P = 0.014). The implantation rate in the first embryo transfer cycle was still significantly higher in the time-lapse group than the standard incubator group after adjusting for age, body mass index, medical centre and embryo status (relative risk 1.11, 95% confidence interval 1.02-1.20, P = 0.020). However, the cumulative implantation rate, live birth rate in the first embryo transfer cycle and cumulative live birth rate were not statistically different between the groups. CONCLUSIONS: The implantation rate in the first embryo transfer cycle was significantly improved in the time-lapse group, but the effect of the time-lapse system on the cumulative implantation rate or cumulative live birth rate was not significant. The embryo assessment method offered by time-lapse systems rather than an undisturbed environment may play an important role in improving the implantation rate in the first embryo transfer cycle. These results are only applicable to young patients.

Transcriptome revealing the dual regulatory mechanism of ethylene on the rhynchophylline and isorhynchophylline in Uncaria rhynchophylla.

Rhynchophylline (RIN) and isorhynchophylline (IRN) are extracted from Uncaria rhynchophylla, which are used to treat Alzheimer's disease. However, the massive accumulation of RIN and IRN in U. rhynchophylla requires exogenous stimulation. Ethylene is a potential stimulant for RIN and IRN biosynthesis, but there is no study on the role of ethylene in RIN or IRN synthesis. This study investigated the regulation of ethylene in RIN and IRN biosynthesis in U. rhynchophylla. An increase in the content of RIN and IRN was observed that could be attributed to the release of ethylene from 18 mM ethephon, while ethylene released from 36 mM ethephon reduced the content of RIN and IRN. The transcriptome and weighted gene co-expression network analysis indicated the up-regulation of seven key enzyme genes related to the RIN/IRN biosynthesis pathway and starch/sucrose metabolism pathway favored RIN/IRN synthesis. In comparison, the down-regulation of these seven key enzyme genes contributed to the reduction of RIN/IRN. Moreover, the inhibition of photosynthesis is associated with a reduction in RIN/IRN. Photosynthesis was restrained owing to the down-regulation of Lhcb1 and Lhcb6 after 36 mM ethephon treatment and further prevented supply of primary metabolites (such as α-D-glucose) for RIN/IRN synthesis. However, uninterrupted photosynthesis ensured a normal supply of primary metabolites at 18 mM ethephon treatment. AP2/ERF1, bHLH1, and bHLH2 may positively regulate the RIN/IRN accumulation, while NAC1 may play a negative regulatory role. Our results construct the potential bidirectional model for ethylene regulation on RIN/IRN synthesis and provide novel insight into the ethylene-mediated regulation of the metabolism of terpenoid indole alkaloids.

Comparative transcriptome analysis revealed the molecular mechanism of the effect of light intensity on the accumulation of rhynchophylline and isorhynchophylline in Uncaria rhynchophylla.

Rhynchophylline (RIN) and isorhynchophylline (IRN), the main medicinal components in plant Uncaria rhynchophylla, have potential effects on Alzheimer's disease. Understanding the influence of environmental factors, especially light intensity, on the production of these active ingredients will help to improve cultivation techniques. Compared with the 100% light intensity (CK), the contents of RIN and IRN in U. rhynchophylla leaves significantly increased at 20% light intensity (HS) after 7 and 21 days. Short-term shading (21d) changed some morphological indicators of U. rhynchophylla, but did not affect its biomass. Transcriptome profile analysis was performed on data from two groups (7 and 21 days) of CK and HS samples and yielded 79,817 unigenes with an average length of 1023 bp. Concurrently, 2391 and 2136 differentially expressed genes were identified in the transcriptome data for, respectively, 7 and 21 days of shade treatment. Notably, unigenes known to be involved upstream in the biosynthesis of RIN and IRN, such as G8O, IO, 7-DLGT, LAMT, TDC, and STR, were mostly upregulated. In addition, 1065 putative transcription factors (TFs) were identified and grouped into 55 TF families; 26 TFs showed differential expression in the shade treatment after 7 and 21 days. HY5 and PIFs, two important TFs of the light signaling pathway, also showed differential expression. This study provides insight into how gene expression was affected by light intensity during RIN and IRN accumulation in U. rhynchophylla. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01142-2.

Respiratory Tract Dysbiosis Is Associated with Worse Outcomes in Mechanically Ventilated Patients.

Rationale: Host inflammatory responses have been strongly associated with adverse outcomes in critically ill patients, but the biologic underpinnings of such heterogeneous responses have not been defined.Objectives: We examined whether respiratory tract microbiome profiles are associated with host inflammation and clinical outcomes of acute respiratory failure.Methods: We collected oral swabs, endotracheal aspirates (ETAs), and plasma samples from mechanically ventilated patients. We performed 16S ribosomal RNA gene sequencing to characterize upper and lower respiratory tract microbiota and classified patients into host-response subphenotypes on the basis of clinical variables and plasma biomarkers of innate immunity and inflammation. We derived diversity metrics and composition clusters with Dirichlet multinomial models and examined our data for associations with subphenotypes and clinical outcomes.Measurements and Main Results: Oral and ETA microbial communities from 301 mechanically ventilated subjects had substantial heterogeneity in α and ß diversity. Dirichlet multinomial models revealed a cluster with low α diversity and enrichment for pathogens (e.g., high Staphylococcus or Pseudomonadaceae relative abundance) in 35% of ETA samples, associated with a hyperinflammatory subphenotype, worse 30-day survival, and longer time to liberation from mechanical ventilation (adjusted P < 0.05), compared with patients with higher α diversity and relative abundance of typical oral microbiota. Patients with evidence of dysbiosis (low α diversity and low relative abundance of "protective" oral-origin commensal bacteria) in both oral and ETA samples (17%, combined dysbiosis) had significantly worse 30-day survival and longer time to liberation from mechanical ventilation than patients without dysbiosis (55%; adjusted P < 0.05).Conclusions: Respiratory tract dysbiosis may represent an important, modifiable contributor to patient-level heterogeneity in systemic inflammatory responses and clinical outcomes.

Sex differences in association between cognitive impairment and clinical correlates in Chinese patients with first-episode drug-naïve schizophrenia.

BACKGROUND: Schizophrenia is a complex mental illness with significant sex differences. Cognitive impairment is common in patients with schizophrenia, even in remission. This study was designed to examine the sex differences in the relationship between cognitive impairment and clinical correlations with first-episode drug-naïve (FEDN) schizophrenia. METHODS: 93 FEDN patients (male/female = 45/48) and 160 controls (male/female = 74/86) were enrolled to compare the sex differences in cognitive functions measured by the MATRICS Consensus Cognitive Battery (MCCB). Positive and Negative Syndrome Scale (PANSS) and Hamilton Depression Scale (HAMD) were used to evaluate patients' clinical symptoms. We compared cognitive impairment with sociodemographic characteristics and measures of different genders, as well as group-by-sex interactions. RESULTS: Our results showed that male patients had significantly lower scores for symbol coding, digital sequence, and verbal learning than female patients, while the healthy controls showed similar sex differences. In female patients, multiple linear regression analysis confirmed that PANSS negative symptoms and general psychopathology scores, HAMD total score, and education level were independent contributors to MCCB total score. In male patients, only education was an independent contributor to MCCB total score. CONCLUSIONS: These findings revealed significant sex differences in cognitive impairments and clinical symptoms in FEDN, which will be worthy of a follow-up study of schizophrenia in the future.

Quantitative Imaging of pN Intercellular Force and Energetic Costs during Collective Cell Migration in Epithelial Wound Healing.

Collective cell migration plays a key role in tissue repair, metastasis, and development. Cellular tension is a vital mechanical regulator during the force-driven cell movements. However, the contribution and mechanism of cell-cell force interaction and energetic costs during cell migration are yet to be understood. Here, we attempted to unfold the mechanism of collective cell movement through quantification of the intercellular tension and energetic costs. The measurement of pN intercellular force is based on a "spring-like" DNA-probe and a molecular tension fluorescence microscopy. During the process of wound healing, the intercellular force along with the cell monolayer mainly originates from actin polymerization, which is strongly related to the cellular energy metabolism level. Intracellular force at different spatial regions of wound and the energetic costs of leader and follower cells were measured. The maximum force and energy consumption are mainly concentrated at the wound edge and dynamically changed along with different stages of wound healing. These results indicated the domination of leader cells other than follower cells during the collective cell migration.

Two New Apotirucallane-Type Triterpenoids from the Pericarp of Toona sinensis and Their Ability to Reduce Oxidative Stress in Rat Glomerular Mesangial Cells Cultured under High-Glucose Conditions.

Hyperglycemia is a strong risk factor for chronic complications of diabetes. Hyperglycemic conditions foster not only the production of reactive oxygen species (ROS), but also the consumption of antioxidants, leading to oxidative stress and promoting the occurrence and progression of complications. During our continuous search for antioxidant constituents from the pericarp of Toona sinensis (A. Juss.) Roem, we isolated two previously unreported apotirucallane-type triterpenoids, toonasinensin A (1) and toonasinensin B (2), together with five known apotirucallane-type triterpenoids (3-7) and two known cycloartane-type triterpenoids (8-9) from the pericarp. Compounds 8-9 were obtained from T. sinensis for the first time. Their structures were characterized based on interpretation of spectroscopic data (1D, 2D NMR, high-resolution electrospray ionization mass spectra, HR-ESI-MS) and comparison to previous reports. Compounds (2, 4, 6, 7, and 9) were able to inhibit proliferation against rat glomerular mesangial cells (GMCs) cultured under high-glucose conditions within a concentration of 80 µM. Compounds (2, 6, and 7) were tested for antioxidant activity attributable to superoxide dismutase (SOD), malondialdehyde (MDA), and ROS in vitro, and the results showed that compounds (2, 6, and 7) could significantly increase the levels of SOD and reduce the levels of MDA and ROS. The current studies showed that apotirucallane-type triterpenoids (2, 6, and 7) might have the antioxidant effects against diabetic nephropathy.

Antivirulence properties and related mechanisms of spice essential oils: A comprehensive review.

In recent decades, reduced antimicrobial effectiveness, increased bacterial infection, and newly emerged microbial resistance have become global public issues, leading to an urgent need to find effective strategies to counteract these problems. Strategies targeting bacterial virulence factors rather than bacterial survival have attracted increasing interest, since the modulation of virulence factors may prevent the development of drug resistance in bacteria. Spices are promising natural sources of antivirulence compounds owing to their wide availability, diverse antivirulence phytochemical constituents, and generally favorable safety profiles. Essential oils are the predominant and most important antivirulence components of spices. This review addresses the recent efforts of using spice essential oils to inhibit main bacterial virulence traits, including the quorum sensing system, biofilm formation, motility, and toxin production, with an intensive discussion of related mechanisms. We hope that this review can provide a better understanding of the antivirulence properties of spice essential oils, which have the potential to be used as antibiotic alternatives by targeting bacterial virulence.

[Correlation of gr/gr and b2/b3 deletions in the AZFc region of the Y-chromosome with recurrent spontaneous abortion].

OBJECTIVE: To investigate the association of gr/gr, b2/b3 and gr/gr with b1-2/b3-4 deletions (repetitions) in the AZFc region of the Y chromosome with recurrent spontaneous abortion (RSA). METHODS: Using the next-generation sequencing technology, we examined the men with indications of Y chromosome microdeletion at our center from June 2017 to March 2018 and excluded the common causes of RSA through inquiry and other related examinations. Totally, 170 cases of AZFc deletion (80 cases of gr/gr deletion, 75 cases of b2/b3 deletion, and 15 cases of gr/gr with b1-2/b3-4 deletion) were detected and included in the case group, and another 328 normal males enlisted as controls. We analyzed the correlation of Y chromosome microdeletions with the incidence rate of RSA. RESULTS: The incidence rate of RSA was significantly higher in the case group than in the normal controls (28.8% ï¼»49/170ï¼½ vs 13.1% ï¼»43/328ï¼½, P < 0.01), 22.5% (18/80) in the gr/gr deletion cases (P < 0.05), 30.7% (23/75) in the b2/b3 deletion cases (P < 0.01), and 53.3% (8/15) in the gr/gr with b1-2/b3-4 deletion cases (P < 0.01), remarkably lower in the gr/gr than in the gr/gr with b1-2/b3-4 deletion subgroup (P < 0.05), but with no statistically significant difference between the other subgroups. CONCLUSIONS: The gr/gr, b2/b3, and gr/gr with b1-2/b3-4 deletions (repetitions) in the AZFc region of the Y chromosome may cause recurrent spontaneous abortion.

Ion Current Rectification in High-Salt Environment from Mesoporous TiO2 Microplug in Situ Grown at the Tip of a Micropipette Induced by Space-Confined Evaporation.

In this work, in situ growth of a titanium dioxide microplug (TDMP) having mesoporous channels at the tip of a glass micropipette induced by space-confined evaporation is reported. Moreover, clear ion current rectification (ICR) of a single-material nanopore in a saturated potassium chloride solution is observed for the first time. TDMP presents an asymmetrical channel structure with the top and bottom apertures of 12.3 ± 6.1 and 42.6 ± 19.7 nm, respectively. TDMP exhibits outstanding ICR capability as the ions get transported through it due to the applied potential. The values for the rectification coefficient (r = log2|I+1 V/I-1 V|) in a saturated KCl solution under acidic (pH of 3.0) and alkaline (pH of 10.0) environments are 1.32 and -0.84, respectively. The intensity and direction of ICR can be adjusted by pH or through the modification of citric acid. Meanwhile, the length and ion transport behavior of TDMP under different growth conditions (time and diameter) were also investigated. TDMP with asymmetric mesoporous channels, maintaining ICR in a saturated salt solution, is expected to expand the application of nanopores in high-salt environments. Furthermore, growth of mesoporous material in the micropipette facilitates the miniaturization of the nanopore device, which further promotes its application potential.

Motion type and knee articular conformity influenced mid-flexion stability of a single radius knee prosthesis.

PURPOSE: Single radius knee implants were introduced to reduce the level of paradoxical anterior femoral translation (AFT) during mid-flexion after total knee arthroplasty. Findings from clinical and experiment studies are inconsistent, which may be due to the different loading conditions and articular conformities of the knee implants studied. The aim of this study is to analyze how variations in these two factors affect the mid-flexion stability of a single radius knee prosthesis. METHODS: Six daily activities (walking, stair ascent, stair descent, sit-to-stand, pivot turn and crossover turn), and three articular conformity ratios (low, moderate and high) were considered. The resulting AFTs from the 18 finite element models were analyzed. RESULTS: For low conformity knees, the worst case activity (the greatest AFT) was sit-to-stand with an AFT of 6.2 mm, while for the moderate conformity the worst case was crossover turn and pivot turn. For high conformity, all activities produced a relatively small AFT ranging from 0 mm to 1.8 mm, which more closely resembles natural knee motion. In addition, no AFT was recorded during stair ascent for all three conformities (low, moderate, high). CONCLUSIONS: This study demonstrated that the amount of AFT is highly dependent on the activity being undertaken and the articular conformity of the knee prosthesis, and the worst case activity depends on the knee conformity. The clinical relevance of this study is that it offers valuable information towards the design of improved knee prostheses and selection of knee implants for clinical use. LEVEL OF EVIDENCE: II.