Premeiotic deletion of Eif2s2 causes oocyte arrest at the early diplotene stage and apoptosis in mice.

Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2), a subunit of the heterotrimeric G protein EIF2, is involved in the initiation of translation. Our findings demonstrate that the depletion of Eif2s2 in premeiotic germ cells causes oocyte arrest at the pachytene and early diplotene stages at 1 day postpartum (dpp) and 5 dpp, respectively, and eventually leads to oocyte apoptosis and failure of primordial follicle formation. Further studies reveal that Eif2s2 deletion downregulates homologous recombination-related and mitochondrial fission-related protein levels, and upregulates the integrated stress response-related proteins and mRNA levels. Consistently, Eif2s2 deletion significantly decreases the expression of dictyate genes and compromises mitochondrial function, characterized by elongated shapes, decreased ATP levels and mtDNA copy number, along with an excessive accumulation of reactive oxygen species (ROS) and mitochondrial superoxide. Furthermore, DNA damage response and proapoptotic protein levels increase, while anti-apoptotic protein levels decrease in Eif2s2-deleted mice. An increase in oocytes with positive cleaved-Caspase-3 and TUNEL signals, alongside reduced Lamin B1 intensity, further indicates oocyte apoptosis. Collectively, Eif2s2 deletion in premeiotic germ cells causes oocyte meiotic arrest at the early diplotene stage by impairing homologous recombination, and eventually leads to oocyte apoptosis mainly through the downregulation of mitochondrial fission-related proteins, ROS accumulation and subsequent DNA damage.

Association between patient adherence and treat-to-target in gout: A cross-sectional study.

The implementation of a treat-to-target (T2T) approach has been widely recommended for achieving optimal outcomes in gout treatment, as substantiated by a wealth of compelling evidence. However, a paucity of knowledge exists regarding the barriers hindering effective T2T management in China. This study seeks to investigate the factors contributing to treatment failure within the context of the T2T strategy. A cross-sectional, multi-center investigation was conducted, involving the completion of electronic questionnaires by outpatients undergoing urate-lowering treatment for a duration exceeding 6 months. These questionnaires encompassed demographic information, disease-related conditions, comorbid conditions, and management. The study analyzed factors associated with serum uric acid levels exceeding 360 µmol/L, poor disease control, and poor medication adherence. A total of 425 valid questionnaires were collected, representing 90.8% of the patients. The T2T implementation rate was 26.82% (n = 114). Factors linked to serum uric acid levels surpassing 360 µmol/L included moderate medication adherence (odds ratio (OR) = 2.35; 95% confidence interval (CI) 1.17-4.77; P = .016), poor medication adherence (OR = 4.63; 95% CI 2.28-9.51; P < .001), and management by general practitioners (OR = 0.60; 95% CI 0.37-0.97; P = .036). The rate of well-controlled patients was 14.35% (n = 61). Predictors of not well controlled encompassed the presence of tophi (OR = 2.48; 95% CI 1.17-5.61; P = .023), general medication adherence (OR = 2.78; 95% CI 1.28-6.05; P = .009), poor medication adherence (OR = 6.23; 95% CI 2.68-14.77; P < .001), and poor patient's perception of gout (OR = 4.07; 95% CI 1.41-13.91; P = .015). A poor medication adherence rate of 55.29% (n = 235) was observed, with lower rates of poor medication adherence associated with the use of febuxostat (OR = 0.35; 95% CI 0.14-0.83; P = .02), uric acid levels exceeding 360 µmol/L (OR = 3.05; 95% CI 1.84-5.12; P = .00), moderate patient education (OR = 2.28; 95% CI 1.29-4.15; P = .01), moderate diet control (OR = 1.98; 95% CI 1.17-3.41; P = .01), and poor diet control (OR = 3.73; 95% CI 1.26-12.83; P = .02). The rate of T2T implementation in China is notably low among patients undergoing urate-lowering treatment of gout beyond 6 months. Importantly, medication adherence demonstrates a significant association with T2T outcomes.

Well-Optimized Conjugated GO-DNA Nanosystem for Sensitive Ratiometric pH Detection in Live Cells.

Intracellular pH is a vital parameter which can reflect the physiological process, and the detection of intracellular pH with a high signal-to-noise ratio (SNR) remains a challenge. Compared to pH biosensors based on a single-wavelength signal, it is much easier to obtain better sensitivity and higher SNR from the biosensors by two-wavelength ratiometric signals. In this study, we used DNA-grafted graphene oxide (GO) to ratiometrically detect intracellular pH ranging from basic to acidic. A high SNR with a 35-fold difference in the ratiometric output has been achieved through careful optimization: (1) A high DNA conjugation yield of 45% has been gained through utilizing the partial double-stranded assembly strategy. (2) Herring sperm DNA (HSD) plays an important role in improving the sensitivity of the nanosystem by purifying and passivating the surface of GO; therefore, the concentration of HSD has been optimized to pursue the most sensitive ratiometric response. Apart from the ultrahigh SNR, fabricated GO-AR-Cy5/IFO-Cy3 exhibited excellent stability and biocompatibility in biological environments. Further experiments demonstrated that the nanosystem worked well in live cells in response to pH changes. It is possible to distinguish small pH differences and realize quantitative detection based on ratiometric fluorescence imaging by laser scanning confocal microscope analysis, which makes the nanosystem a promising candidate for further biological study and clinical applications.

Efficient preparation of kaolinite/methanol intercalation composite by using a Soxhlet extractor.

Kaolinite/methanol intercalation composite (KMe) is a key precursor for preparing clay-based inorganic/organic hybrid materials and kaolinite nanoscrolls. However, synthesis of KMe is a time and methanol dissipative process and the complexity of this process also limits its further applications. In this study, Soxhlet extractor was introduced to synthesize an intercalation composite and KMe was efficiently synthesized in a Soxhlet extractor through a continuous displacement process by using kaolinite/DMSO intercalation composite (KD) as a precursor. The formation process of kaolinite/methanol intercalation composite was studied by X-ray diffraction (XRD) and infrared spectroscopy (IR). The results showed that the DMSO in kaolinite could be completely displaced by methanol in this process and the preparation of KMe could be completed in 8 hours, which was far faster than the reported methods. Moreover, methanol used in this process could be recycled. Furthermore, the resulting material could be successfully used to prepare kaolinite nanoscrolls in high yield.

A common anchor facilitated GO-DNA nano-system for multiplex microRNA analysis in live cells.

The design of a nano-system for the detection of intracellular microRNAs is challenging as it must fulfill complex requirements, i.e., it must have a high sensitivity to determine the dynamic expression level, a good reliability for multiplex and simultaneous detection, and a satisfactory biostability to work in biological environments. Instead of employing a commonly used physisorption or a full-conjugation strategy, here, a GO-DNA nano-system was developed under graft/base-pairing construction. The common anchor sequence was chemically grafted to GO to base-pair with various microRNA probes; and the hybridization with miRNAs drives the dyes on the probes to leave away from GO, resulting in "turned-on" fluorescence. This strategy not only simplifies the synthesis but also efficiently balances the loading yields of different probes. Moreover, the conjugation yield of GO with a base-paired hybrid has been improved by more than two-fold compared to that of the conjugation with a single strand. We demonstrated that base-paired DNA probes could be efficiently delivered into cells along with GO and are properly stabilized by the conjugated anchor sequence. The resultant GO-DNA nano-system exhibited high stability in a complex biological environment and good resistance to nucleases, and was able to accurately discriminate various miRNAs without cross-reaction. With all of these positive features, the GO-DNA nano-system can simultaneously detect three miRNAs and monitor their dynamic expression levels.

pH-Responsive Graphene Oxide-DNA Nanosystem for Live Cell Imaging and Detection.

The interaction between graphene oxide (GO) and DNA is very sensitive to the environment. For example, under acidic conditions, the affinity of GO for DNA is enhanced, weakening the capability of GO to distinguish DNAs with different conformations. This effect has impeded the development of sensitive pH biosensors based on GO-DNA nanosystems. In this work, we systematically studied the affinity between GO and i-motif forming oligonucleotides (IFOs) at different pH values and developed a herring sperm DNA (HSD) treatment method. Using this method, HSD occupies the surface of GO, compromising the attractive force of GO that is significantly enhanced under acidic conditions. As a result, the ability of GO to distinguish between "open" and "closed" IFOs is successfully generalized to a wider pH range. Finally, a pH-sensitive GO-IFO nanosystem was fabricated that showed excellent sensing ability both in vitro and for intracellular pH detection. Because the interaction between GO and DNA is the basis for constructing GO-DNA biosensors, the strategy developed in this work shows great potential to be applied in a variety of other GO-DNA sensing systems.

Bile acid-surfactant interactions at the liquid crystal/aqueous interface.

The interaction between bile acids and surfactants at interfaces plays an important role in fat digestion. In this paper, we study the competitive adsorption of cholic acid (CA) at the sodium dodecyl sulfate (SDS)-laden liquid crystal (LC)/aqueous interface formed with cyanobiphenyl (nCB, n = 5-8) and the mixture of 5CB with 4-(4-pentylcyclohexyl)benzonitrile (5PCH). We find that the critical concentration of CA required to displace SDS from the interface linearly decreases from 160 µM to 16 µM by reducing the alkyl chain length of nCB from n = 8 to n = 5 and from 16 µM to 1.5 µM by increasing the 5PCH concentration from 0 wt% to 19 wt% in the 5PCH-5CB binary mixture. Our results clearly demonstrate that the sensitivity of 5PCH-5CB mixtures for monitoring the interaction between CA and SDS at the LC/aqueous interface can be increased by one order of magnitude, compared to 5CB.

Morphology and shape control of porous silica nanostructures with dual-templating approaches.

There has been great interest in the synthesis of porous silica nanostructures because of their potential applications in catalysis, adsorption, molecular separation, and biomedical engineering. In this paper, we report the synthesis of porous silica nanostructures with varied morphologies and shapes from two-phase systems by using lithocholic acid (LCA) and cetyltrimethylammmonium bromide (CATB) or LCA and Pluronic F127 in the lower ammonia aqueous phase as dual directing agents and tetraethylsiloxane (TEOS) in the upper oil phase as a silica precursor. Porous silica spheres are formed by using LCA/CTAB as a dual directing agent, while silica fibers with pits are synthesized by using LCA/F127 as a dual directing agent. The straight-to-helical shape transition of silica fibers with pits can be achieved by increasing the ammonia concentration in the low aqueous phase.

Self-assembly of J-aggregate nanotubes and their applications for sensing dopamine.

J-aggregates are an attractive supramolecular structure with interesting excitation properties found in the light-harvesting antenna of green sulfur bacteria. To structurally mimic the light-harvesting antenna, we synthesize J-aggregate nanotubes with a sharp and intense absorption band (J-band) by the coassembly of lithocholic acid (LCA) and 3,3'-dipropylthiadicarbocyanine iodide (DiSC3(5)) in aqueous solution. We show that the J-aggregate nanotubes can be used as a supramolecular probe for the sensitive and selective detection of dopamine (DA) in phosphate buffered saline (PBS) solution with the detection limit of ∼0.4 nM by simply observing the intensity change of the J-band due to the efficient photoinduced electron transfer from the J-aggregate nanotubes to the adsorbed DA.