Protective anti-gB neutralizing antibodies targeting two vulnerable sites for EBV-cell membrane fusion.

Epstein-Barr virus (EBV) infects more than 90% of the world's adult population and accounts for a significant cancer burden of epithelial and B cell origins. Glycoprotein B (gB) is the primary fusogen essential for EBV entry into host cells. Here, we isolated two EBV gB-specific neutralizing antibodies, 3A3 and 3A5; both effectively neutralized the dual-tropic EBV infection of B and epithelial cells. In humanized mice, both antibodies showed effective protection from EBV-induced lymphoproliferative disorders. Cryoelectron microscopy analyses identified that 3A3 and 3A5 bind to nonoverlapping sites on domains D-II and D-IV, respectively. Structure-based mutagenesis revealed that 3A3 and 3A5 inhibit membrane fusion through different mechanisms involving the interference with gB-cell interaction and gB activation. Importantly, the 3A3 and 3A5 epitopes are major targets of protective gB-specific neutralizing antibodies elicited by natural EBV infection in humans, providing potential targets for antiviral therapies and vaccines.

A hsa_circ_001726 axis regulated by E2F6 contributes to metastasis of hepatocellular carcinoma.

BACKGROUND: CircRNAs participate in the development of hepatocellular carcinoma (HCC). This work aims to explore the key tumor promoting circRNA as a gene therapy target. METHODS: The differentially expressed gene circRNAs in HCC tumor tissues was identified by mining GSE121714 dataset. EdU staining, wound healing, transwell invasion assay, TUNEL staining and western blotting examined proliferation, migration, invasion, apoptosis and epithelial mesenchymal transition (EMT). Xenograft mouse model and orthotopic transplantation tumor mouse model were constructed to verify the role of hsa_circ_001726 in growth and metastasis of HCC. The relationship among CCT2, E2F6, hsa_circ_001726, miR-671-5p and PRMT9 was identified by RNA-fluorescence in situ hybridization, luciferase reporter assay and RNA Immunoprecipitation. RESULTS: Eleven differentially expressed circRNAs were found in HCC tumors. Among them, hsa_circ_001726 was highly expressed in HCC tumors and cells, which was transcribed from CCT2. As a transcription factor of CCT2, E2F6 knockdown inactivated CCT2 promoter and reduced hsa_circ_001726 expression. Moreover, hsa_circ_001726 elevated PRMT9 expression by sponging miR-671-5p, and then activated Notch signaling pathway. Additionally, hsa_circ_001726 deficiency repressed malignant phenotypes of HCC cells, including proliferation, migration, invasion, EMT and apoptosis. In vivo, hsa_circ_001726 deficiency reduced tumor growth and lung metastasis of HCC in xenograft mouse models and orthotopic transplantation tumor mouse models. CONCLUSION: Hsa_circ_001726 functioned as an oncogene in HCC, which was derived from CCT2 and regulated by E2F6. Hsa_circ_001726 elevated PRMT9 expression by sponging miR-671-5p, and then activated Notch signaling pathway, thereby accelerating malignant phenotypes of HCC. Therefore, targeting hsa_circ_001726 may be a new avenue for HCC treatment.

Intrauterine interventions options for preventing recurrence after hysteroscopic adhesiolysis: a systematic review and network meta-analysis of randomized controlled trials.

PURPOSE: Recurrence of adhesions after hysteroscopic adhesiolysis is a challenging clinical problem without a unified management approach. Therefore, we conducted a network meta-analysis that considered both direct and indirect comparisons between interventions to identify optimal strategies for preventing recurrence. METHODS: We searched for research trials published up to July 2023 from PubMed, Embase and the Cochrane Database. We selected randomized controlled trials comparing the use of different interventions for the prevention of adhesion recurrence, with no language or regional restrictions. We used random-effects models to assess odds ratios (OR) and mean difference (MD) with 95% confidence intervals (CI). Adverse events associated with the interventions were also assessed. This study was registered on PROSPERO, CRD42023449068. RESULTS: Data from 21 randomized controlled trials involving 2406 patients were synthesized, including interventions with balloon, amnion, platelet-rich plasma (PRP), intrauterine device (IUD), hyaluronic acid (HA), platelet-rich fibrin (PRF), and granulocyte colony-stimulating factor (G-CSF). The top 5 interventions for change in AFS scores were: PRP + Balloon (MD = 5.44; 95% CI, 2.63-8.25), Amnion + Balloon (MD = 5.08; 95% CI, 2.71-7.44), IUD + Balloon (MD = 4.89; 95% CI, 2.49-7.30), HA + Balloon (MD = 3.80; 95% CI, 1.78-5.82), and G-CSF + Balloon (MD = 3.84; 95% CI, 1.05-6.63). There were no statistically significant differences between interventions in the recurrence rate of moderate-to-severe uterine adhesions and the clinical pregnancy rate. Most interventions were safe. CONCLUSIONS: To our knowledge, this is the most comprehensive network meta-analysis to date of interventions for preventing postoperative intrauterine adhesion recurrence. Our results indicate that PRP + Balloon seems to be the most effective approach.

A Neutralizing Antibody Targeting gH Provides Potent Protection against EBV Challenge In Vivo.

Epstein-Barr virus (EBV) is an oncogenic herpesvirus that is associated with 200,000 new cases of cancer and 140,000 deaths annually. To date, there are no available vaccines or therapeutics for clinical usage. Recently, the viral heterodimer glycoprotein gH/gL has become a promising target for the development of prophylactic vaccines against EBV. Here, we developed the anti-gH antibody 6H2 and its chimeric version C6H2, which had full neutralizing activity in epithelial cells and partial neutralizing activity in B cells. C6H2 exhibited potent protection against lethal EBV challenge in a humanized mouse model. The cryo-electron microscopy (cryo-EM) structure further revealed that 6H2 recognized a previously unidentified epitope on gH/gL D-IV that is critical for viral attachment and subsequent membrane fusion with epithelial cells. Our results suggest that C6H2 is a promising candidate in the prevention of EBV-induced lymphoproliferative diseases (LPDs) and may inform the design of an EBV vaccine. IMPORTANCE Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that establishes lifelong persistence and is related to multiple diseases, including cancers. Neutralizing antibodies (NAbs) have proven to be highly effective in preventing EBV infection and subsequent diseases. Here, we developed an anti-EBV-gH NAb, 6H2, which blocked EBV infection in vitro and in vivo. This 6H2 neutralizing epitope should be helpful to understand EBV infection mechanisms and guide the development of vaccines and therapeutics against EBV infection.

Arginine methylation of HSPA8 by PRMT9 inhibits ferroptosis to accelerate hepatitis B virus-associated hepatocellular carcinoma progression.

BACKGROUND: The hepatitis B virus X (HBx) protein is an established cause of hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC). Whether arginine methylation regulates ferroptosis involved in HBx-induced HCC progression has not been reported. This study aimed to explore whether HBx-regulated protein arginine methyltransferase 9 (PRMT9) mediates the involvement of ferroptosis in the development of HCC. METHODS AND RESULTS: HBx inhibited ferroptosis through promoting PRMT9 expression in HCC cells. PRMT9 suppressed ferroptosis to accelerate HCC progression in vivo. PRMT9 targeted HSPA8 and enhanced arginine methylation of HSPA8 at R76 and R100 to regulate ferroptosis in HCC. HSPA8 overexpression altered the transcriptome profile of HepG2 cells, in particular, ferroptosis and immune-related pathways were significantly enriched by differentially expressed genes, including CD44. HSPA8 overexpression up-regulated CD44 expression and knockdown of CD44 significantly reversed the inhibition of ferroptosis caused by PRMT9 overexpression. CONCLUSIONS: In conclusion, HBx/PRMT9/HSPA8/CD44 axis is a vital signal pathway regulating ferroptosis in HCC cells. This study provides new opportunities and targets for the treatment of HBV-induced HCC.

AIE-doped Poly(Ionic Liquid) Photonic Spheres for the Discrimination of Psychoactive Substances.

Drugs of abuse has drawn intense attention due to increasing concerns to public health and safety. The construction of a sensing platform with the capability to identify them remains a big challenge because of the limitations of synthetic complexity, sensing scope and receptor extendibility. Here a kind of poly(ionic liquid) (PIL) photonic crystal spheres doped with aggregation-induced emission (AIE) luminogens was developed. As diverse noncovalent interactions involve in PIL moieties, the single sphere shows different binding affinity to a broad range of psychoactive substances. Furthermore, the dual-channel signals arising from photonic crystal structures and sensitive AIE-luminogens provide high-dimensional information for discriminative detection of targets, even for molecules with slight structural differences. More importantly, such single sphere sensing platform could be flexibly customized through ion-exchange, showing great extendibility to fabricate high-efficiency/high-throughput sensing arrays without tedious synthesis.

High-density lipoprotein cholesterol modifies the association between blood lead and uric acid: results from NHANES 2005-2016.

BACKGROUND: The association between blood lead (PbB) and uric acid (SUA) remains unclear in US adults without a high level of lead exposure. Additionally, the effects of high-density lipoprotein cholesterol (HDL-C) modifying this association are still unclear. Therefore, this study aims to assess the effect of modification of high-density lipoprotein cholesterol on the association between PbB and SUA. METHOD: This research analyzed National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2016. Through several screenings, 18,578 participants over the age of 20 were eligible for the analysis. Multivariable linear regression was used to evaluate the association between PbB and SUA. By having stratified participants based on the HDL-C intake category (low HDL-C intake < 50 mg/dl; high HDL-C intake ≥ 50 mg/dl), effect modification by HDL-C was assessed through a likelihood ratio test between PbB and SUA. RESULT: Multivariable linear regression indicated that PbB positively affects SUA (ß = 0.19, 95% CI 0.16-0.22). The relationship between PbB and SUA was different in the low and high HDL-C intake group (ß 0.12 95% Cl 0.08-0.16 vs. ß 0.26 95% Cl 0.22 ~ - 0.30). Furthermore, high-density lipoprotein cholesterol significantly modified the relationship between PbB and SUA in all models which indicates that the interaction of lead exposure and HDL-C is more dangerous than the sum of the individual effects. CONCLUSIONS: Our study shows that high-density lipoprotein cholesterol and blood lead have an interactive effect on increasing uric acid, which may have great importance for clinical medication.

Maternal circulating exosomal miR-185-5p levels as a predictive biomarker in patients with recurrent pregnancy loss.

PURPOSE: The aim of this study was to explore the predictive role of microRNAs (miRNAs) from maternal serum exosomes in early recurrent pregnancy loss (RPL) and the related mechanism in early pregnancy. METHODS: Maternal serum was collected from pregnant women with RPL history or women with ongoing pregnancy (OP); serum exosomes were extracted and identified. Differentially expressed (DE) miRNAs in exosomes were screened by RNA sequencing and further validated by qRT-PCR. Next, the predictive value of exosomal miRNA and the clinical indicators for subsequent miscarriage in RPL patients were evaluated. Additionally, we verified the regulatory relationship between miR-185-5p and vascular endothelial growth factor (VEGF) in decidual natural killer (dNK) cells by overloading or inhibiting the exosomal miR-185-5p level in trophoblast cells. RESULTS: The miRNA sequencing revealed 43 DE miRNAs between OP and RPL patients. The five most significant DE miRNAs (miR-22-3p, miR-185-5p, miR-335-3p, miR-362-5p, and miR-378a-3p) were selected for identification, and miR-185-5p was increased in RPL patients. The area under curve (AUC) of the receiver operating characteristic was 0.925 when using miR-185-5p as a biomarker for subsequent miscarriage in RPL patients. In addition, miR-185-5p in exosomes secreted from HTR-8 cells reduces VEGF expression of dNK cells. CONCLUSIONS: The current study, for the first time, successfully constructed the correlation between maternal circulating exosomal miR-185-5p expression pattern and RPL, which may be involved in the pathogenesis of RPL by downregulating the VEGFA of dNK cells and perturbing angiogenesis at the maternal-fetal interface.

T cell epitope screening of Epstein-Barr virus fusion protein gB.

Glycoprotein B (gB) is an essential fusion protein for the Epstein-Barr virus (EBV) infection of both B cells and epithelial cells and is thus a promising target antigen for a prophylactic vaccine to prevent or reduce EBV-associated disease. T cell responses play key roles in the control of persistent EBV infection and in the efficacy of a vaccine. However, to date, T cell responses to gB have been characterized for only a limited number of human leukocyte antigen (HLA) alleles. Here, we screened gB T cell epitopes in 23 healthy EBV carriers and ten patients with nasopharyngeal cancer (NPC) using a peptide library spanning the entire gB sequence. We identified twelve novel epitopes in the context of seven new HLA restrictions that are common in Asian populations. Two epitopes, gB214-223 and gB840-849, restricted by HLA-B*58:01 and B*38:02, respectively, elicited specific CD8+ T cell responses to inhibit EBV-driven B cell transformation. Interestingly, gB-specific CD8+ T cells were more frequent in healthy viral carriers with EBV reactivation than in those without EBV reactivation, indicating that EBV reactivation in vivo stimulates both humoral (VCA-gp125-IgA) and cellular responses to gB. We further found that most gB epitopes are conserved among different EBV strains. Our study broadens the diversity and HLA restrictions of gB epitopes and suggests that gB is a common target of T cell responses in healthy viral carriers with EBV reactivation. In particular, the precisely mapped and conserved gB epitopes provide valuable information for prophylactic vaccine development.ImportanceT cells are crucial for the control of persistent EBV infection and the development of EBV-associated diseases. The EBV gB protein is essential for virus entry into B cells and epithelial cells and is thus a target antigen for vaccine development. Understanding T cell responses to gB is important for subunit vaccine design. Herein, we comprehensively characterized T cell responses to full-length gB. Our results expand the available gB epitopes and HLA restrictions, particularly those common in Asian populations. Furthermore, we showed that gB-specific CD8+ T cells inhibit B cell transformation ex vivo and that gB-specific CD8+ T cell responses in vivo may be associated with intermittent EBV reactivation in asymptomatic viral carriers. These gB epitopes are highly conserved among geographically separated EBV strains. Precisely mapped and conserved T cell epitopes may contribute to immune monitoring and to the development of a gB subunit vaccine.

A high-throughput neutralizing assay for antibodies and sera evaluation against Epstein-Barr virus.

BACKGROUND: Epstein-Barr virus (EBV) is a wide-spread human herpesvirus that is highly associated with infectious mononucleosis and several malignancies. Evaluation of EBV neutralizing antibody titers is important for serological studies, vaccine development and monoclonal antibody screening. The traditional method based on antibody inhibition of EBV transformation of B cells is very time-consuming. A more practical flow cytometry-based (FCM) approach to evaluate neutralizing titers is not amenable to achieving high-throughput evaluation of large-scale samples. A high-throughput approach is urgently needed. RESULTS: Here, we present a rapid and high-throughput method based on high content imaging system (HCIS) analysis. EBV titers determined by the HCIS-based assay were similar to those obtained by the FCM-based assay. Neutralizing titers of sera and monoclonal antibodies measured by the HCIS-based assay strongly correlated with titers measured by the FCM-based assay. HCIS assays showed a strong correlation between B cell infection neutralizing titers and the anti-gp350 IgG titers in healthy EBV carriers and monkey sera. Finally, anti-gHgL IgG titers from sera of healthy EBV carriers significantly correlated with epithelial cell infection neutralizing titers. CONCLUSIONS: This HCIS-based assay is a high-throughput assay to determine viral titers and evaluate neutralizing potentials of sera and monoclonal antibodies. This HCIS-based assay will aid the development of vaccines and therapeutic monoclonal antibody against EBV.

Higher exogenous gonadotrophin doses increase the risk of small for gestational age singletons after fresh embryo transfers.

RESEARCH QUESTION: A negative relationship has been reported between exogenous gonadotrophin dosage and the live birth rate in IVF. It is unclear whether total gonadotrophin dosage is associated with neonatal outcomes. The effect of exogenous gonadotrophin dosage on neonatal outcomes of singletons after fresh embryo transfer (FET) was investigated. DESIGN: A retrospective cohort study of 2020 live singletons evaluating neonatal outcomes. All patients underwent autologous IVF cycles between 1 August 2016 and 30 April 2020 and delivered a live singleton birth after FET. Patients with polycystic ovary syndrome were excluded. Patients were divided according to total gonadotrophin dose: group 1: ≤1800 IU; group 2: 1801-2500 IU; and group 3: >2500 IU. RESULTS: After adjusting for confounding factors by multiple regression models, the adjusted rate of small for gestational age (SGA) was significantly higher in group 3 (adjusted [a]OR 2.25, 95% CI 1.24 to 4.08). The risk of SGA increased 2.25 times when total gonadotrophin dose exceeded 2500 IU versus gonadotrophin doses below 1800 IU. The hierarchical analysis showed that an increased rate of SGA infants occurred in the GnRH agonist long protocol (aOR 2.09, 95% CI 1.02 to 5.17) and in the antagonist protocol (aOR 2.75, 95% CI 1.05 to 7.22). CONCLUSIONS: For patients without polycystic ovary syndrome, an excessive total gonadotrophin dose during ovarian stimulation, i.e. more than 2500 IU, may negatively affect neonatal outcomes by increasing the SGA rate of singletons after FET. Therefore, total gonadotrophin dose administered during ovarian stimulation should preferably not exceed 2500 IU.

Molecular analysis of enthesopathy in a mouse model of hypophosphatemic rickets.

The bone tendon attachment site known as the enthesis comprises a transitional zone between bone and tendon, and plays an important role in enabling movement at this site. X-linked hypophosphatemia (XLH) is characterized by impaired activation of vitamin D, elevated serum FGF23 levels and low serum phosphate levels, which impair bone mineralization. Paradoxically, an important complication of XLH is mineralization of the enthesis (enthesopathy). Studies were undertaken to identify the cellular and molecular pathways important for normal post-natal enthesis maturation and to examine their role during the development of enthesopathy in mice with XLH (Hyp). The Achilles tendon entheses of Hyp mice demonstrate an expansion of hypertrophic-appearing chondrogenic cells by P14. Post-natally, cells in wild-type and Hyp entheses similarly descend from scleraxis- and Sox9-expressing progenitors; however, Hyp entheses exhibit an expansion of Sox9-expressing cells, and enhanced BMP and IHH signaling. These results support a role for enhanced BMP and IHH signaling in the development of enthesopathy in XLH.

Detection of atmospheric temperature by using polarization high-spectral-resolution lidar.

In order to achieve high signal-to-noise ratio by using small laser energy and telescope aperture, we present a polarization filter in high-spectral-resolution lidar (HSRL) for the measurement of atmospheric temperature. Compared with the filter method in a traditional HSRL in which the intensity of the return signal is split into the different transmission channel of a discriminator, the advantage of this filter system is that the intensity of the return signal is fully utilized for each discriminator channel, and the return signal changes the polarization state of the light without loss of intensity when it is incident on the two Rayleigh channels. In addition, the daytime detection capability of HSRL is improved by using a polarization optical scheme to suppress the solar background light. The advantages of the polarization filter are proven by the theoretical calculations using the Stokes vector and a Mueller matrix. In detection experiments of atmospheric temperature, the detection height is 4 km at night and 2.5 km during the day by using the pulsed energy of 50 mJ and telescope diameter of 250 mm. The results are in good agreement with the data detected by radiosonde.

Creation of Nonspherical Microparticles through Osmosis-Driven Arrested Coalescence of Microfluidic Emulsions.

Droplet-based microfluidics enable the production of emulsions and microparticles with spherical shapes, but the high-throughput fabrication of nonspherical emulsions and microparticles still remains challenging because interfacial tension plays a dominant role during preparation. Herein, ionic liquids (ILs) containing salts, which possess sufficient osmotic pressure to realize water transport and phase separation, are introduced as inner cores of oil-in-oil-in-water double emulsions and it is shown that nonspherical emulsions can be constructed by osmosis-driven arrested coalescence of inner cores. Subsequently, ultraviolet polymerization of the nonspherical emulsions leads to nonspherical microparticles. By tailoring the number, composition, and size of inner cores as well as coalescence time, a variety of nonspherical shapes such as dumbbell, rod, spindle, snowman, tumbler, three-pointed star, triangle, and scalene triangle are created. Importantly, benefitting from excellent solvency of ILs, this system can serve as a general platform to produce nonspherical microparticles made from different materials. Moreover, by controlling the osmotic pressure, programmed coalescence of inner cores in double emulsions is realizable, which indicates the potential to build microreactors. Thus, a simple and high-throughput strategy to create nonspherical microparticles with arrested coalescence shapes is developed for the first time and can be further used to construct novel materials and microreactors.

Supraphysiological serum oestradiol negatively affects birthweight in cryopreserved embryo transfers: a retrospective cohort study.

RESEARCH QUESTION: Previous studies have demonstrated a negative relationship between peak oestradiol and low birthweight in IVF. However, it is hard to distinguish which aspect influenced by supraphysiological oestradiol concentrations fundamentally contributes to the low birthweight seen during IVF. This study therefore aimed to investigate whether birthweight was associated with an effect of oestradiol on oocytes. DESIGN: Oocytes are the only component exposed to the high-oestradiol environment in vitrified-warmed embryo transfer (VET) cycles. A retrospective cohort study of 431 infertile women was therefore carried out to evaluate the relationship between peak oestradiol concentration during controlled ovarian stimulation (COS) and birthweight in full-term singletons born after VET. The effect size was calculated using multivariable regression analysis. RESULTS: In this cohort, the mean peak oestradiol concentration was 4186.6 ± 1215.0 pg/ml, the mean number of oocytes retrieved was 11.5 ± 5.4, the mean length of ovarian stimulation was 11.3 ± 2.1 days and the mean birthweight was 3441.8 ± 466.1 g. The results indicated that peak oestradiol concentration was negatively correlated with birthweight in full-term singletons born after VET (adjusted ß -5.0, 95% confidence interval [CI] -9.2 to -0.7). The effect size indicated that for every 100 pg/ml increase in peak oestradiol concentration, birthweight decreased by 5.0 g. The P for trend value was 0.038. CONCLUSIONS: Peak serum oestradiol during COS is negatively associated with birthweight. This model proposes a novel concept as well as new evidence that the effect on birthweight is due to the primary influence of a high oestradiol concentration on oocytes during COS.

The impact of peak estradiol during controlled ovarian stimulation on the cumulative live birth rate of IVF/ICSI in non-PCOS patients.

OBJECTIVE: The study aimed to investigate the impact of the peak E2 level during controlled ovarian hyperstimulation (COS) on the cumulative live birth rate (cLBR) in non-PCOS women with normal ovarian reserve. MATERIALS AND METHODS: Women between 20 and 39 years were included. Donor cycles and patients who never experienced embryo transfer were excluded. Multivariable regression and smooth curve fitting were applied for statistical analysis. RESULTS: A total of 1141 patients were included. The mean age, basal AFC, peak E2 level, and number of retrieved oocyte were 30.0 ± 3.7 years old, 16.8 ± 6.7, 3911.0 ± 1302.9 pg/ml, and 13.6 ± 5.5, respectively. In the overall population of the cohort, cLBR, miscarriage rate, and preterm birth rate were 66.9%, 7.4%, and 13.7%, respectively. The results of multivariable regression analysis failed to show the impact of peak E2 on the cLBR [OR (95%CI) 0.995 (0.982, 1.009), P = 0.486]. However, the result of smooth curve fitting indicated that when the peak E2 was lower than 2185 pg/ml, the cLBR increased about 12% with 100 pg/ml increasing of the peak E2. When the peak E2 was higher than 6136 pg/ml, the cLBR decreased about 10% with 100 pg/ml increasing of the peak E2. CONCLUSION: We concluded that the peak E2 level on hCG trigger day is associated with the cLBR in a segmental pattern. There should be an appropriate range of the peak E2 level during COS to achieve a relative best cLBR in non-PCOS patients using stimulating protocol mainly based on GnRH agonist; however, the cutoff value must vary in different centers.

Clinical outcomes of frozen embryo versus fresh embryo transfer following in vitro fertilization: a meta-analysis of randomized controlled trials.

PURPOSE: To examine available data from randomized controlled trials to assess if the freeze-all embryo and subsequent frozen-thawed embryo transfer (FET) results in better clinical outcomes than fresh embryo transfer (ET). METHODS: Meta-analysis. RESULTS: We conducted an electronic literature search on PubMed and Embase databases and manually supplemented another 2 articles from relevant citations. Seven studies were finally included in the meta-analysis,including 1141 women who underwent fresh embryo transfer and 1079 who underwent frozen embryo transfer. The results of the meta-analysis suggested that the live birth rate [RR (95% CI) 1.18 (1.08-1.30), P = 0.0003] and clinical pregnancy rate [RR (95% CI) 1.10 (1.02-1.19), P = 0.02] were significantly higher in FET group. Miscarriage rate [RR (95% CI) 0.62 (0.48-0.80), P = 0.0002], and moderate to severe OHSS occurrence rate [RR (95% CI) 0.22 (0.12 to 0.39), P < 0.00001] were significantly lower in FET group. Differences of biochemical pregnancy rate, ongoing pregnancy rate and implantation rate between the two groups did not reach the statistical significance. CONCLUSIONS: Our results suggest that the IVF/ICSI with FET is more efficient and less risky for OHSS compared with ET. However, we should comprehensively inform patients with advantages, disadvantages and potential risks related to embryo cryopreservation, and carefully assess their fertility conditions to make the most beneficial clinical decision.

Efficient Construction of Well-Defined Multicompartment Porous Systems in a Modular and Chemically Orthogonal Fashion.

A microfluidic assembly approach was developed for efficiently producing hydrogel spheres with reactive multidomains that can be employed as an advantageous platform to create spherical porous networks in a facile manner with well-defined multicompartments and spatiotemporally controlled functions. This strategy allows for not only large scale fabrication of various robust hydrogel microspheres with controlled size and porosity, but also the domains embedded in hydrogel network could be introduced in a modular manner. Additionally, the number of different domains and their ratio could be widely variable on demand. More importantly, the reactive groups distributed in individual domains could be used as anchor sites to further incorporate functional units in an orthogonal fashion, leading to well-defined multicompartment systems. The strategy provides a new and efficient route to construct well-defined functional multicompartment systems with great flexibility and extendibility.

Resveratrol inhibits oral squamous cell carcinoma through induction of apoptosis and G2/M phase cell cycle arrest.

The present study was performed to investigate the effect of resveratrol (trans-3,4',5-trihydroxystilbene) present as a natural phytoalexin in grapes, peanuts, and red wine on oral squamous cancer cell lines, SCC-VII, SCC-25, and YD-38. MTS assay and flow cytometry, respectively, were used for the analysis of inhibition of cell proliferation and apoptosis. Western blot analysis was performed to examine the effect of resveratrol on the expression of proteins associated with cell cycle regulation. The results revealed a concentration- and time-dependent inhibition of proliferation in all the three tested cell lines on treatment with resveratrol. The IC50 of resveratrol for SCC-VII, SCC-25, and YD-38 cell lines was found to be 0.5, 0.7, and 1.0 µg/ml, respectively, after 48-h treatment. Examination of the cell cycle analysis showed that resveratrol treatment induced cell cycle arrest in the G2/M phase and enhanced the expression of phospho-cdc2 (Tyr 15), cyclin A2, and cyclin B1 in the oral squamous cell carcinoma (OSCC) cells. It also caused a marked increase in the percentage of apoptotic cells as revealed by the fluorescence-activated cell sorting analysis. Thus, resveratrol exhibits inhibitory effect on the proliferation of OSCC oral cancer cells through the induction of apoptosis and G2/M phase cell cycle arrest.

The tRNA(Gly) T10003C mutation in mitochondrial haplogroup M11b in a Chinese family with diabetes decreases the steady-state level of tRNA(Gly), increases aberrant reactive oxygen species production, and reduces mitochondrial membrane potential.

Mitochondrial diabetes originates mainly from mutations located in maternally transmitted, mitochondrial tRNA-coding genes. In a genetic screening program of type 2 diabetes conducted with a Chinese Han population, we found one family with suggestive maternally transmitted diabetes. The proband's mitochondrial genome was analyzed using DNA sequencing. Total 42 known nucleoside changes and 1 novel variant were identified, and the entire mitochondrial DNA sequence was assigned to haplogroup M11b. Phylogenetic analysis showed that a homoplasmic mutation, 10003T>C transition, occurred at the highly conserved site in the gene encoding tRNA(Gly). Using a transmitochondrial cybrid cell line harboring this mutation, we observed that the steady-state level of tRNA(Gly) significantly affected and the amount of tRNA(Gly) decreased by 97%, production of reactive oxygen species was enhanced, and mitochondrial membrane potential, mtDNA copy number and cellular oxygen consumption rate were remarkably decreased compared with wild-type cybrid cells. The homoplasmic 10003T>C mutation in the mitochondrial tRNA(Gly) gene suggested to be as a pathogenesis-related mutation which might contribute to the maternal inherited diabetes in the Han Chinese family.