Tektin bundle interacting protein, TEKTIP1, functions to stabilize the tektin bundle and axoneme in mouse sperm flagella.

Tektins are microtubule inner proteins (MIPs) and localize at the inside lumen of doublet microtubules (DMTs) of cilia/flagella. TEKTIP1, a newly identified protein by cryo-electron microscopy (cryo-EM), is proposed to be localized at the center of the tektin bundle and hypothesized to recruit tektins or stabilize the bundle. However, the physiological role of TEKTIP1 is unknown. In this study, we generated Tektip1-knockout (Tektip1-/-) mice and showed that they were male subfertile primarily due to reduced sperm motility. A high percentage of sperm from Tektip1-/- mice showed moderately disorganized axoneme structures and abnormal flagellar waveforms. TEKTIP1 predominately interacted with TEKT3 among tektins. Loss of TEKTIP1 partially disturbed the organization of tektin bundle by mainly affecting the native status of TEKT3 and its interaction with other tektins. Collectively, our study reveals the physiological role and potential molecular mechanism of TEKTIP1 in axonemal structure and sperm motility, highlights the importance of MIPs in stabilizing DMTs, and suggests a potential relevance of TEKTIP1 deficiency to human asthenospermia. Tektip1-/- mice will be an excellent animal model to study the DMT organization of sperm flagella using cryo-EM in future.

Abundance of Low-Energy Oxygen Vacancy Pairs Dictates the Catalytic Performance of Cerium-Stabilized Zirconia.

Cerium-stabilized zirconia (Ce1-xZrxOy, CZO) is renowned for its superior oxygen storage capacity (OSC), a key property long believed to be beneficial to catalytic oxidation reactions. However, 50% Ce-containing CZO recorded with the highest OSC has disappointingly poor performance in catalytic oxidation reactions compared to those with higher Ce contents but lower OSC ability. Here, we employ global neural network (G-NN)-based potential energy surface exploration methods to establish the first ternary phase diagram for bulk structures of CZO, which identifies three critical compositions of CZO, namely, 50, 60, and 80% Ce-containing CZO that are thermodynamically stable under typical synthetic conditions. 50% Ce-containing CZO, although having the highest OSC, exhibits the lowest O vacancy (Ov) diffusion rate. By contrast, 60% Ce-containing CZO, despite lower OSC (33.3% OSC compared to that of 50% Ce-containing CZO), reaches the highest Ov diffusion ability and thus offers the highest CO oxidation catalytic performance. The physical origin of the high performance of 60% Ce-containing CZO is the abundance of energetically favorable Ov pairs along the ⟨110⟩ direction, which reduces the energy barrier of Ov diffusion in the bulk and promotes O2 activation on the surface. Our results clarify the long-standing puzzles on CZO and point out that 60% Ce-containing CZO is the most desirable composition for typical CZO applications.

Recycling the Spent LiNi1- x - yMnxCoyO2 Cathodes for High-Performance Electrocatalysts toward Both the Oxygen Catalytic and Methanol Oxidation Reactions.

The traditional recycling methods of the spent lithium ion batteries (LIBs) involve the intricate and cumbersome steps. This work proposes a facile method of acid leaching followed by the sulfurization treatment to achieve the high Li leaching efficiency, and obtain high-performance multi-function electrocatalysts for oxygen reduction (ORR), oxygen evolution (OER), and methanol oxidation reactions (MOR) from the spent LIB ternary cathodes. By this method, the Li leaching efficiency from the spent LIB ternary cathode can reach 98.3%, and the transition metal sulfide heterostructures (LNMCO-H-450S) consisting MnS, NiS2, and NiCo2S4 phases can be obtained. LNMCO-H-450S shows the superior bifunctional oxygen catalytic activities with ORR half-wave potential of 0.763 V and OER potential at 10 mA cm-2 of 1.561 V, surpassing most of the state-of-the-art electrocatalysts. LNMCO-H-450S also demonstrates the superior MOR catalytic activity with the potential at 100 mA cm-2 being 1.37 V. Using LNMCO-H-450S as the oxygen catalyst, this work can construct the aqueous and solid-state zinc-air batteries with high power density of 309 and 257 mW cm-2, respectively. This work provides a promising strategy for the efficient recovery of Li, and reutilization of Ni, Co, and Mn from the spent LIB ternary cathodes.

Reduction of Backward Scatterings at the Low-Coherence Kunwu Laser Facility.

We report the first experimental observation on the reduction of backward scatterings by an instantaneous broadband laser with 0.6% bandwidth in conditions of interest for inertial confinement fusion at the low-coherence Kunwu laser facility. The backscatter of stimulated Brillouin scattering (SBS) was robustly reduced by half at intensities of 1-5×10^{14} W/cm^{2} with the 0.53-µm broadband laser in comparison with the monochromatic laser. As SBS dominates energy loss of laser-plasma interactions, the reduction of that demonstrates the enhancement of laser-target coupling by the use of broadband laser. The mitigation of filamentation leads to the reduction of stimulated Raman backscattering at low intensities. In addition, the three-halves harmonic emission was reduced with the broadband laser as well.

The role of age and AMH on cumulative live birth rates over multiple frozen-thawed embryo transfer cycles: a study based on low prognosis patients of POSEIDON 3 and 4 groups.

BACKGROUND: Among the POSEIDON criteria, group 3 and group 4 have an expected low prognosis. For those patients with inadequate ovary reserve, embryo accumulated from consecutive oocyte retrieval cycles for multiple frozen-thawed embryo transfers (FET) has become more common. It is necessary to inform them of the pregnancy outcomes after single or multiple FET cycles before the treatment. However few studies about cumulative live birth rate (CLBR) for those with low prognosis have been reported. METHODS: This retrospective study included 4712 patients undergoing frozen embryo transfer cycles from July 2015 to August 2020. Patients were stratified as POSEIDON group 3, group 4, control 1 group (< 35 years) and control 2 group (≥ 35 years). The primary outcome is CLBRs up to six FET cycles and the secondary outcomes were LBRs per transfer cycle. Optimistic approach was used for the analysis of CLBRs and the depiction of cumulative incidence curves. RESULTS: Under optimistic model analyses, control 1 group exhibited the highest CLBR (93.98%, 95%CI 91.63-95.67%) within 6 FET cycles, followed by the CLBR from women in POSEIDON group 3(92.51%, 95%CI 77.1-97.55)was slightly lower than that in control 1 group. The CLBR of POSEIDON group 4(55% ,95%CI 39.34-70.66%)was the lowest and significantly lower than that of control 2 group(88.7%, 95%CI 80.68-96.72%). Further, patients in POSEIDON group 4 reached a CLBR plateau after 5 FET cycles. CONCLUSIONS: The patients of POSEIDON group 3 may not be considered as traditional "low prognosis" in clinical practice as extending the number of FET cycles up to 6 can archive considerably CLBR as control women. While for the POSEIDON group 4, a simple repeat of the FET cycle is not recommended after four failed FET cycles, some strategies such as PGT-A may be beneficial.

Association between TB delay and TB treatment outcomes in HIV-TB co-infected patients: a study based on the multilevel propensity score method.

BACKGROUND: HIV-tuberculosis (HIV-TB) co-infection is a significant public health concern worldwide. TB delay, consisting of patient delay, diagnostic delay, treatment delay, increases the risk of adverse anti-TB treatment (ATT) outcomes. Except for individual level variables, differences in regional levels have been shown to impact the ATT outcomes. However, few studies appropriately considered possible individual and regional level confounding variables. In this study, we aimed to assess the association of TB delay on treatment outcomes in HIV-TB co-infected patients in Liangshan Yi Autonomous Prefecture (Liangshan Prefecture) of China, using a causal inference framework while taking into account individual and regional level factors. METHODS: We conducted a study to analyze data from 2068 patients with HIV-TB co-infection in Liangshan Prefecture from 2019 to 2022. To address potential confounding bias, we used a causal directed acyclic graph (DAG) to select appropriate confounding variables. Further, we controlled for these confounders through multilevel propensity score and inverse probability weighting (IPW). RESULTS: The successful rate of ATT for patients with HIV-TB co-infection in Liangshan Prefecture was 91.2%. Total delay (OR = 1.411, 95% CI: 1.015, 1.962), diagnostic delay (OR = 1.778, 95% CI: 1.261, 2.508), treatment delay (OR = 1.749, 95% CI: 1.146, 2.668) and health system delay (OR = 1.480 95% CI: (1.035, 2.118) were identified as risk factors for successful ATT outcome. Sensitivity analysis demonstrated the robustness of these findings. CONCLUSIONS: HIV-TB co-infection prevention and control policy in Liangshan Prefecture should prioritize early treatment for diagnosed HIV-TB co-infected patients. It is urgent to improve the health system in Liangshan Prefecture to reduce delays in diagnosis and treatment.

Cell-Penetrating Peptide TAT-HuR-HNS3 Suppresses Proinflammatory Gene Expression via Competitively Blocking Interaction of HuR with Its Partners.

Proinflammatory cytokines/chemokines are commonly regulated by RNA-binding proteins at posttranscriptional levels. Human Ag R (HuR)/embryonic lethal abnormal vision-like 1 (ELAVL1) is one of the well-characterized RNA-binding proteins that increases the stability of short-lived mRNAs, which encode proinflammatory mediators. HuR employs its nucleocytoplasmic shuttling sequence (HNS) domain, interacting with poly(ADP-ribose) polymerase 1 (PARP1), which accounts for the enhanced poly-ADP-ribosylation and cytoplasmic shuttling of HuR. Also by using its HNS domain, HuR undergoes dimerization/oligomerization, underlying the increased binding of HuR with proinflammatory cytokine/chemokine mRNAs and the disassociation of the miRNA-induced silencing complex from the targets. Therefore, competitively blocking the interactions of HuR with its partners may suppress proinflammatory mediator production. In this study, peptides derived from the sequence of the HuR-HNS domain were synthesized, and their effects on interfering HuR interacting with PARP1 and HuR itself were analyzed. Moreover, cell-penetrating TAT-HuR-HNS3 was delivered into human and mouse cells or administered into mouse lungs with or without exposure of TNF-α or LPS. mRNA levels of proinflammatory mediators as well as neutrophil infiltration were evaluated. We showed that TAT-HuR-HNS3 interrupts HuR-PARP1 interaction and therefore results in a lowered poly-ADP-ribosylation level and decreased cytoplasmic distribution of HuR. TAT-HuR-HNS3 also blocks HuR dimerization and promotes Argonaute 2-based miRNA-induced silencing complex binding to the targets. Moreover, TAT-HuR-HNS3 lowers mRNA stability of proinflammatory mediators in TNF-α-treated epithelial cells and macrophages, and it decreases TNF-α-induced inflammatory responses in lungs of experimental animals. Thus, TAT-HuR-HNS3 is a promising lead peptide for the development of inhibitors to treat inflammation-related diseases.

An Ultralow-concentration and Moisture-resistant Electrolyte of Lithium Difluoro(oxalato)borate in Carbonate Solvents for Stable Cycling in Practical Lithium-ion Batteries.

The electrolyte concentration not only impacts the battery performance but also affects the battery cost and manufacturing. Currently, most studies focus on high-concentration (>3 M) or localized high-concentration electrolytes (~1 M); however, the expensive lithium salt imposes a major concern. Most recently, ultralow concentration electrolytes (<0.3 M) have emerged as intriguing alternatives for battery applications, which feature low cost, low viscosity, and extreme-temperature operation. However, at such an early development stage, many works are urgently needed to further understand the electrolyte properties. Herein, we introduce an ultralow concentration electrolyte of 2 wt % (0.16 M) lithium difluoro(oxalato)borate (LiDFOB) in standard carbonate solvents. This electrolyte exhibits a record-low salt/solvent mass ratio reported to date, thus pointing to a superior low cost. Furthermore, this electrolyte is highly compatible with commercial Li-ion materials, forming stable and inorganic-rich interphases on the lithium cobalt oxide (LiCoO2) cathode and graphite anode. Consequently, the LiCoO2-graphite full cell demonstrates excellent cycling performance. Besides, this electrolyte is moisture-resistant and effectively suppresses the generation of hydrogen fluoride, which will markedly facilitate the battery assembly and recycling process under ambient conditions.

Blastocyst quality and reproductive and perinatal outcomes: a multinational multicentre observational study.

STUDY QUESTION: Does the transfer of single low-grade blastocysts result in acceptable reproductive and perinatal outcomes compared to the transfer of single good-grade blastocysts? SUMMARY ANSWER: The transfer of single low-grade blastocysts resulted in a reduced live birth rate of around 30% (14% for very low-grade blastocysts) compared to 44% for single good-grade blastocysts, but does not lead to more adverse perinatal outcomes. WHAT IS KNOWN ALREADY: It is known that low-grade blastocysts can result in live births. However, the current studies are limited by relatively small sample sizes and single-centre designs. Furthermore, evidence on perinatal outcomes after transferring low-grade blastocysts is limited. STUDY DESIGN, SIZE, DURATION: We conducted a multi-centre, multi-national retrospective cohort study of 10 018 women undergoing 10 964 single blastocyst transfer cycles between 2009 and 2020 from 14 clinics across Australia, China, and New Zealand. PARTICIPANTS/MATERIALS, SETTING, METHODS: Blastocysts were graded individually based on assessment of the morphology and development of the inner cell mass (ICM) and trophectoderm (TE), and were grouped into three quality categories: good- (AB, AB, or BA), moderate- (BB), and low-grade (grade C for ICM or TE) blastocysts. CC blastocysts were individually grouped as very low-grade blastocysts. Logistic regression with generalized estimating equation was used to analyse the association between blastocyst quality and live birth as well as other reproductive outcomes. Binomial, multinomial logistic, or linear regression was used to investigate the association between blastocyst quality and perinatal outcomes. Odds ratio (OR), adjusted OR (aOR), adjusted regression coefficient, and their 95% CIs are presented. Statistical significance was set at P < 0.05. MAIN RESULTS AND THE ROLE OF CHANCE: There were 4386 good-grade blastocysts, 3735 moderate-grade blastocysts, and 2843 low-grade blastocysts were included in the analysis, for which the live birth rates were 44.4%, 38.6%, and 30.2%, respectively. Compared to good-grade blastocysts, the live birth rate of low-grade blastocysts was significantly lower (aOR of 0.48 (0.41-0.55)). Very low-grade blastocysts were associated with an even lower live birth rate (aOR 0.30 (0.18-0.52)) and their absolute live birth rate was 13.7%. There were 4132 singleton live births included in the analysis of perinatal outcomes. Compared with good-grade blastocysts, low-grade blastocysts had comparable preterm birth rates (<37 weeks, aOR 1.00 (0.65-1.54)), birthweight Z-scores (adjusted regression coefficient 0.02 (0.09-0.14)), and rates of very low birth weight (<1500 g, aOR 0.84 (0.22-3.25)), low birth weight (1500-2500 g, aOR 0.96 (0.56-1.65)), high birth weight (>4500 g, aOR 0.93 (0.37-2.32)), small for gestational age (aOR 1.63 (0.91-2.93)), and large for gestational age (aOR 1.28 (0.97-1.70)). LIMITATIONS, REASONS FOR CAUTION: Due to the nature of the retrospective design, residual confounding could not be excluded. In addition, the number of events for some perinatal outcomes was small. Between-operator and between-laboratory variations in blastocyst assessment were difficult to control. WIDER IMPLICATIONS OF THE FINDINGS: Patients undergoing IVF should be informed that low-grade blastocysts result in a lower live birth rate, however they do not increase the risk of adverse perinatal outcomes. Further research should focus on the criteria for embryos that should not be transferred and on the follow-up of long-term outcomes of offspring. STUDY FUNDING/COMPETING INTEREST(S): H.Z. is supported by a Monash Research Scholarship. B.W.J.M. is supported by a NHMRC Investigator grant (GNT1176437). R.W. is supported by an NHMRC Emerging Leadership Investigator grant (2009767). B.W.J.M. reports consultancy, travel support, and research funding from Merck. The other authors do not have competing interests to disclose. TRIAL REGISTRATION NUMBER: N/A.

Assessing the influencing factors of out-of-pocket costs on tuberculosis in Sichuan Province: a cross-sectional study.

BACKGROUND: Although diagnosis and treatment services for tuberculosis (TB) are provided free of charge in most countries, direct non-medical and indirect costs due to absenteeism, also place a significant burden on patients and their families. Sichuan Province has the second highest incidence of TB in China, with an incidence of approximately 100 cases per 100 000 people. However, there are limited research on out-of-pocket expenditure (OOPE) and its influencing factors in TB patients in Sichuan Province. METHODS: A retrospective cross-sectional study was conducted on TB patients in designated medical institutions for TB in Sichuan Province from 2017-2021. A face-to-face questionnaire was conducted to obtain the information related to hospitalization of patients, and the multi-level regression model was used to analyse the factors that influence OOPE and total out-of-pocket expenditure (TOOPE) of TB patients. RESULTS: A total of 2644 patients were investigated, and 74.24% of TB patients and their families experienced catastrophic total costs due to TB. The median total cost was 9223.37 CNY (1429.98 USD), in which the median direct and indirect costs of TB patients were 10185.00 CNY (1579.07 USD) and 2400.00 CNY (372.09 USD), respectively, and indirect costs contributed to 43% of total costs. The median OOPE and TOOPE costs were 6024.00 CNY (933.95 USD) and 11890.50 CNY (1843.49 USD), respectively. OOPE and TOOPE had common influencing factors including whether the patient's family had four or more members, a history of hospitalization, combination with other types of TB, the number of visits before diagnosis, and co-occurrence with chronic disease. CONCLUSIONS: The OOPE and TOOPE for TB patients and their families in Sichuan Province are still heavy. In the long run, it is necessary to strengthen education and awareness campaigns on TB related knowledge, disseminate basic medical knowledge to the public, improve healthcare-seeking behavior, and enhance the healthcare infrastructure to improve the accuracy of TB diagnosis and reduce the significant OOPE and TOOPE faced by TB patients and their families in Sichuan Province.

Fast time-evolving random polarization beam smoothing for laser-driven inertial confinement fusion.

We propose a random polarization smoothing method for low-coherence laser to obtain focal spot with random polarization that evolves rapidly in sub-picosecond timescales. Random polarization smoothing is realized by a half-aperture wave plate with sufficient thickness. The degree of polarization and polarization evolution of the focal spot are studied theoretically. The calculation results show that random polarization smoothing can make the polarization of focal spot evolve rapidly and randomly in time and space. Experimentally, the polarization of the focal spot of low-coherence laser with random polarization smoothing is measured by a single-shot polarimeter. The measurement results show that the degree of polarization of the focal spot is reduced to 0.22 on average, which proves the effectiveness of random polarization smoothing. The random polarization smoothing technique on low-coherence laser is expected to reduce the laser plasmas instability through its multi-dimensional random evolution properties.

Full-aperture random polarization smoothing for a low-coherence laser facility.

Two new random polarization smoothing methods using full-aperture elements are proposed on low-coherence lasers, one using birefringent wedge and one using flat birefringent plate. By designing the crystal axis direction and wedge angle of the birefringent plates, the methods can selectively introduce time delay and spatial displacement, so as to obtain fast random evolution of transient polarization by utilizing low spatiotemporal coherence of the laser focal field. Both methods avoid the near field discontinuity and can be used under high fluence. The method using birefringent wedge can slightly improve focal spot uniformity, and the method using flat birefringent plate can obtain non-polarization with DOP lower than 2%. Theoretical studies show that the resulting focal polarization evolves rapidly on sub-picosecond timescales and rapidly covers the entire Poincaré sphere. The method using birefringent wedge is achieved in experiment. The results show that the degree of polarization of the focal spot is reduced from 1 to 0.27, which proves the effectiveness of the full-aperture random polarization smoothing. The full-aperture random polarization smoothing can generate a focal field very close to unpolarized thermal light, which is expected to suppress the laser plasmas instability.

Long-Term Environmental Enrichment Relieves Dysfunctional Cognition and Synaptic Protein Levels Induced by Prenatal Inflammation in Older CD-1 Mice.

A mounting body of evidence suggests that prenatal inflammation may enhance the rate of age-associated cognitive decline and may involve aberrant amounts of synaptic proteins in the hippocampus, including synaptotagmin-1 (Syt1) and activity-regulated cytoskeleton-associated protein (Arc). However, little is known about the specific impact of adolescent environmental enrichment (EE) on age-associated cognitive decline and the changes in synaptic proteins caused by prenatal inflammation. In this study, CD-1 mice in late pregnancy were given intraperitoneal doses of lipopolysaccharide (LPS, 50 µg/kg) or normal saline. Offspring arising from LPS dams were divided into a LPS group and a LPS plus EE (LPS-E) group. The LPS-E mice were exposed to EE from 2 months of age until the end of the experiment (3 or 15 months old). The Morris water maze (MWM) was used to assess the spatial learning and memory capacities of experimental mice, while western blotting and RNA-scope were used to determine the expression levels of Arc and Syt1 in the hippocampus at the protein and mRNA levels, respectively. Analysis revealed that at 15 months of age, the control mice experienced a reduction in cognitive ability and elevated expression levels of Arc and Syt1 genes when compared to control mice at 3 months of age. The LPS-E group exhibited better cognition and lower protein and mRNA levels of Arc and Syt1 than mice in the LPS group of the same age. However, the enriched environment mitigated but did not counteract, the effects of prenatal inflammation on cognitive and synaptic proteins when tested at either 3 or 15 months of age. Our findings revealed that long-term environmental enrichment improved the expression levels of synaptic proteins in CD-1 mice and that this effect was linked to the dysfunctional cognition caused by prenatal inflammation; this process may also be involved in the reduction of hippocampal Arc and Syt1 gene expression.

Sustainable and Green Synthesis of Waste-Biomass-Derived Carbon Dots for Parallel and Semi-Quantitative Visual Detection of Cr(VI) and Fe3.

Carbon dot (CD)-based multi-mode sensing has drawn much attention owing to its wider application range and higher availability compared with single-mode sensing. Herein, a simple and green methodology to construct a CD-based dual-mode fluorescent sensor from the waste biomass of flowers of wintersweet (FW-CDs) for parallel and semi-quantitative visual detection of Cr(VI) and Fe3+ was firstly reported. The FW-CD fluorescent probe had a high sensitivity to Cr(VI) and Fe3+ with wide ranges of linearity from 0.1 to 60 µM and 0.05 to 100 µM along with low detection limits (LOD) of 0.07 µM and 0.15 µM, respectively. Accordingly, the FW-CD-based dual-mode sensor had an excellent parallel sensing capacity toward Cr(VI) and Fe3+ with high selectivity and strong anti-interference capability by co-using dual-functional integration and dual-masking strategies. The developed parallel sensing platform was successfully applied to Cr(VI) and Fe3+ quantitative detection in real samples with high precision and good recovery. More importantly, a novel FW-CD-based fluorescent hydrogel sensor was fabricated and first applied in the parallel and semi-quantitative visual detection of Cr(VI) and ferrous ions in industrial effluent and iron supplements, further demonstrating the significant advantage of parallel and visual sensing strategies.

Sensitizing the Luminescence of Lanthanide-Doped Nanoparticles over 1500 nm for High-Contrast and Deep Imaging of Brain Injury.

Real-time and in situ visualization of cerebrovascular dysfunction is significant for studying brain injury, which however, is restricted by the complex brain structure and limited imaging strategies. Luminescence imaging in NIR-IIb region (1500-1700 nm) is a promising tool owing to its merits including deep penetration, high resolution, and fast data acquisition. Unfortunately, a luminescent material in this region with sufficient brightness and biocompatibility is scarce. Herein, Ag2Se quantum dot-sensitized lanthanide-doped nanocrystals (QDs-LnNCs) with emission beyond 1500 nm were fabricated to image the cerebrovascular structure and hemodynamics in ischemic stroke and traumatic brain injury. The sensitization by QDs provided an over 100-fold enhanced brightness of LnNCs and a remarkable penetration depth of 11 mm. Dynamic information of blood perfusion and flow rates were acquired and the damage of the blood-brain barrier in the two injury models was investigated. Our results proved QDs-LnNCs as a kind of competent nanomaterial for noninvasive brain imaging.

TRIB3 regulates FSHR expression in human granulosa cells under high levels of free fatty acids.

BACKGROUND: Granulosa cells (GCs) in cumulus oophorus highly express follicle stimulating hormone receptor (FSHR), which is the most important mediator of both estradiol synthesis and oocyte maturation. Obese women have elevated free fatty acids (FFAs) levels in their follicular fluids and decreased FSHR expression in GCs, which is related to an altered protein kinase B/glycogen synthase kinase 3ß (Akt/GSK3ß) signaling pathway. Such FFA increases accompany 3-fold rises in pseudokinase 3 (TRIB3) expression and reduce the Akt phosphorylation status in both the human liver and in insulinoma cell lines. Therefore, in a high FFA environment, we determined if TRIB3 mediates regulation of FSHR via the Akt/GSK3ß signaling pathway in human GCs. METHODS: GCs from women undergoing in vitro fertilization were collected and designated as high and low FFAs cohorts based on their follicular fluid FFA content. GCs with low FFA levels and a human granulosa-like tumor (KGN) cell line were exposed to palmitic acid (PA), which is a dominate FFA follicular fluid constituent. The effects were assessed of this substitution on the Akt/GSK3ß signaling pathway activity as well as the expressions of TRIB3 and FSHR at both the gene and protein levels by qPCR, Western blot and immunofluorescence staining analyses. Meanwhile, the individual effects of TRIB3 knockdown in KGN cells and p-AKT inhibitors were compared to determine the mechanisms of FFA-induced FSHR downregulation. RESULTS: The average FSH dose consuming per oocyte (FSH dose/oocyte) was elevated and Top embryo quality ratio was decreased in women with high levels of FFAs in their follicular fluid. In these women, the GC TRIB3 and ATF4 protein expression levels were upregulated which was accompanied by FSHR downregulation. Such upregulation was confirmed based on corresponding increases in their gene expression levels. On the other hand, the levels of p-Akt decreased while p-GSK3ß increased in the GCs. Moreover, TRIB3 knockdown reversed declines in FSHR expression and estradiol (E2) production in KGN cells treated with PA, which also resulted in increased p-Akt levels and declines in the p-GSK3ß level. In contrast, treatment of TRIB3-knockdown cells with an inhibitor of p-Akt (Ser473) resulted in rises in the levels of both p-GSK3ß as well as FSHR expression whereas E2 synthesis fell. CONCLUSIONS: During exposure to a high FFA content, TRIB3 can reduce FSHR expression through stimulation of the Akt/GSK3ß pathway in human GCs. This response may contribute to inducing oocyte maturation.

Enzymatically inactive OGG1 binds to DNA and steers base excision repair toward gene transcription.

8-Oxoguanine DNA glycosylase1 (OGG1)-initiated base excision repair (BER) is the primary pathway to remove the pre-mutagenic 8-oxo-7,8-dihydroguanine (8-oxoG) from DNA. Recent studies documented 8-oxoG serves as an epigenetic-like mark and OGG1 modulates gene expression in oxidatively stressed cells. For this new role of OGG1, two distinct mechanisms have been proposed: one is coupled to base excision, while the other only requires substrate binding of OGG1--both resulting in conformational adjustment in the adjacent DNA sequences providing access for transcription factors to their cis-elements. The present study aimed to examine if BER activity of OGG1 is required for pro-inflammatory gene expression. To this end, Ogg1/OGG1 knockout/depleted cells were transfected with constructs expressing wild-type (wt) and repair-deficient mutants of OGG1. OGG1's promoter enrichment, oxidative state, and gene expression were examined. Results showed that TNFα exposure increased levels of oxidatively modified cysteine(s) of wt OGG1 without impairing its association with promoter and facilitated gene expression. The excision deficient K249Q mutant was even a more potent activator of gene expression; whereas, mutant OGG1 with impaired substrate recognition/binding was not. These data suggested the interaction of OGG1 with its substrate at regulatory regions followed by conformational adjustment in the adjacent DNA is the primary mode to modulate inflammatory gene expression.

High-power, low-coherence laser driver facility.

We report the first (to the best of our knowledge) high-power, low-coherence Nd:glass laser delivering kilojoule pulses with a coherent time of 249 fs and a bandwidth of 13 nm, achieving the 63%-efficiency second-harmonic conversion of the large-aperture low-coherence pulse and good beam smoothing effect. It provides a new type of laser driver for laser plasma interaction and high energy density physics research.

Transvaginal ovarian drilling followed by controlled ovarian stimulation from the next day improves ovarian response for the poor responders with polycystic ovary syndrome during IVF treatment: a pilot study.

BACKGROUND: Poor response patients with PCOS who are not susceptible to gonadotropin stimulation are more likely to have canceled cycles or poor clinical outcomes during IVF treatment. However, some limitations exist in the present therapies. In this study, we evaluated the effects of using the transvaginal ovarian drilling (TVOD) followed by controlled ovarian stimulation (COS) from the second day of these poor responders. METHODS: During IVF, 7 poor responders with PCOS and 28 PCOS patients (14 normal and 14 high responders) were recruited. All patients received COS with the gonadotropin-releasing hormone antagonist protocol. For the poor responders, after undergoing 10 to 14 days of ovulation induction with no response, the TVOD was applied and then ovarian stimulation was performed from the next day at the same gonadotropin dose. Serum samples during COS and follicular fluid samples from the dominant follicles on the oocyte pick-up (OPU) day in all three groups were collected. Besides, follicular fluid from small follicles (diameter < 1 cm) in the normal and high responders on the OPU day and those in the poor responders on the TVOD day were gathered. Hormonal levels were examined in all samples using immunometric assays. RESULTS: All the poor responders restored ovary response after receiving TVOD. There was no significant difference in the stimulation duration, total gonadotrophin dose used and the clinical outcomes among the three groups. The body mass index, serum and follicular levels of anti-Müllerian hormone (AMH) and testosterone in poor responders were higher than those in the other two groups, and the application of TVOD significantly decreased the levels of AMH and testosterone in both serum and follicular fluid. CONCLUSIONS: TVOD followed by ovulation induction from the next day is effective and convenient for poor responders with PCOS. The decline of AMH and testosterone resulted from TVOD may be the main reason resulting in the recovery of ovary sensitivity to gonadotropins. The small sample size is the primary limitation of this study, future studies using a large population cohort and monitoring the long-term outcomes of this strategy will be required. TRIAL REGISTRATION: ChiCTR1900023612. Registered 04 June 2019-Retrospectively registered.

Spatio-temporal analysis of socio-economic characteristics for pulmonary tuberculosis in Sichuan province of China, 2006-2015.

BACKGROUND: The disease burden caused by pulmonary tuberculosis (TB) in Sichuan province still persisted at a high level, and large spatial variances were presented across regional distribution disparities. The socio-economic factors were suspected to affect the population of TB notification, we aimed to describe TB case notification rate (CNR) and identify which factors influence TB epidemic are necessary for the prevention and control of the disease in Sichuan province. METHODS: A retrospective cross-sectional study and an ecological spatial analysis was conducted to quantify the presence and location of spatial clusters of TB by the Moran's I index and examined these patterns with socio-economic risk factors by hierarchical Bayesian spatio-temporal model. RESULTS: A total of 630,009 pulmonary TB cases were notified from 2006 to 2015 in 181 counties of Sichuan province. The CNR decreased year by year since 2007, from 88.70 to 61.37 per 100,000 persons. The spatial heterogeneities of CNR were observed during the study periods. Global Moran's I index varied from 0.23 to 0.44 with all P-value < 0.001. The Bayesian spatio-temporal model with parametric spatio-temporal interactions was chosen as the best model according to the minimum of Deviance Information Criterion (DIC)(19,379.01), and in which the quadratic form of time was taken. The proportion of age group and education year were all associated with CNR after adjusting the spatial effect, temporal effect and spatio-temporal interactions. TB CNR increased by 10.2% [95% credible interval (CI): 6.7-13.7%] for every 1-standard-deviation increase in proportion of age group and decreased by 23% (95% CI: 13.7-32.7%) for every 1-standard-deviation increase in education year. CONCLUSIONS: There were spatial clusters of TB notification rate in Sichuan province from 2006 to 2015, and heavy TB burden was mainly attributed to aging and low socioeconomic status including poor education. Thus, it is more important to pay more attention to the elderly population and improve socioeconomic status including promoting education level in Sichuan province to reduce the TB burden.