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The extraction of lithium and potassium from salt lakes has led to the generation of substantial amounts of magnesium-rich waste streams. These by-products, with their high magnesium content, have contributed to severe environmental degradation in salt lake regions. Therefore, recovering and utilizing magnesium from salt lake resources is a crucial challenge for achieving sustainable development. In this study, magnesium and lithium were separated from evaporated brine—obtained via solar pond technology—using membrane electrolysis. Magnesium was converted into Mg(OH)2 as a flame retardant, while lithium was refined into battery-grade Li2CO3. The final products exhibited high purity, exceeding 99.5% for Mg(OH)2 and 99.99% for Li2CO3. This work systematically investigated the influence of electrolysis temperature on the physicochemical properties of Mg(OH)2 extracted via membrane electrolysis. The variation in electrolyte temperature was also analyzed in relation to other process parameters, such as electrolyte concentration, current density, and processing time. Results demonstrated that the electrolysis process could maintain a favorable operating temperature through self-heating, even under ambient conditions. Using this electrolysis approach for magnesium–lithium separation from brine, extraction rates of 95.86% for magnesium and 67.46% for lithium were achieved.

The 3′ region extraction and deep sequencing (3′READS) method accurately identifies cleavage and polyadenylation sites, avoiding common artifacts and detecting sites in A-rich contexts. It was used to greatly expand the number of characterized sites in the mouse genome, including those in long noncoding RNAs. Alternative cleavage and polyadenylation (APA) generates diverse mRNA isoforms. We developed 3′ region extraction and deep sequencing (3′READS) to address mispriming issues that commonly plague poly(A) site (pA) identification, and we used the method to comprehensively map pAs in the mouse genome. Thorough annotation of gene 3′ ends revealed over 5,000 previously overlooked pAs (∼8% of total) flanked by A-rich sequences, underscoring the necessity of using an accurate tool for pA mapping. About 79% of mRNA genes and 66% of long noncoding RNA genes undergo APA, but these two gene types have distinct usage patterns for pAs in introns and upstream exons. Quantitative analysis of APA isoforms by 3′READS indicated that promoter-distal pAs, regardless of intron or exon locations, become more abundant during embryonic development and cell differentiation and that upregulated isoforms have stronger pAs, suggesting global modulation of the 3′ end–processing activity in development and differentiation.

Immune checkpoint blockade of the inhibitory immune receptors PD-L1, PD-1 and CTLA-4 has emerged as a successful treatment strategy for several advanced cancers. Here we demonstrate that miR-424(322) regulates the PD-L1/PD-1 and CD80/CTLA-4 pathways in chemoresistant ovarian cancer. miR-424(322) is inversely correlated with PD-L1, PD-1, CD80 and CTLA-4 expression. High levels of miR-424(322) in the tumours are positively correlated with the progression-free survival of ovarian cancer patients. Mechanistic investigations demonstrated that miR-424(322) inhibited PD-L1 and CD80 expression through direct binding to the 3′-untranslated region. Restoration of miR-424(322) expression reverses chemoresistance, which is accompanied by blockage of the PD-L1 immune checkpoint. The synergistic effect of chemotherapy and immunotherapy is associated with the proliferation of functional cytotoxic CD8+ T cells and the inhibition of myeloid-derived suppressive cells and regulatory T cells. Collectively, our data suggest a biological and functional interaction between PD-L1 and chemoresistance through the microRNA regulatory cascade. Resistance to chemotherapy occurs in many ovarian cancer cases. Here, the authors show that mir-424(322) expression restores the sensitivity of ovarian cancer cells to chemotherapy by blocking the PD-L1 immune checkpoint, and find that combining immunotherapy and chemotherapy has a synergistic effect.

The tubeless percutaneous nephrolithotomy (PCNL) is highly favored by endourological urologists for its advantages in patient experience and length of hospital stay. However, there is currently no guideline or consensus that precisely describes tubeless PCNL. This study explores tubeless PCNL from two aspects: patient selection and technical improvements. Clinical data of 40 cases of conventional PCNL and tubeless PCNL patients operated by the same surgeon between December 2023 and April 2024 were analyzed. The changes in the preoperative and postoperative renal function, hemoglobin and inflammatory markers were evaluated, and the operative time, pain scores, and length of hospital stay were also included. Both groups of patients achieved complete stone clearance (100%). Compared to the conventional PCNL group, the tubeless PCNL group had lower pain scores (P < 0.001) and shorter hospital stays (P = 0.005). There were no statistically significant differences between the two groups in terms of operative time (P = 0.83), renal functional impact (P = 0.699), hemoglobin reduction (P = 0.93), and changes in inflammatory markers (P > 0.05). Tubeless PCNL demonstrated better patient experience and shorter hospital stays. Tubeless PCNL patients were strictly selected according to our criteria and operated based on traditional experience and the improved technical standards in this study. Tubeless PCNL is safe and feasible under these conditions. Retrospectively registered: 0620, August, 2024.

Alternative cleavage and polyadenylation (APA) results in mRNA isoforms containing different 3' untranslated regions (3'UTRs) and/or coding sequences. How core cleavage/polyadenylation (C/P) factors regulate APA is not well understood. Using siRNA knockdown coupled with deep sequencing, we found that several C/P factors can play significant roles in 3'UTR-APA. Whereas Pcf11 and Fip1 enhance usage of proximal poly(A) sites (pAs), CFI-25/68, PABPN1 and PABPC1 promote usage of distal pAs. Strong cis element biases were found for pAs regulated by CFI-25/68 or Fip1, and the distance between pAs plays an important role in APA regulation. In addition, intronic pAs are substantially regulated by splicing factors, with U1 mostly inhibiting C/P events in introns near the 5' end of gene and U2 suppressing those in introns with features for efficient splicing. Furthermore, PABPN1 inhibits expression of transcripts with pAs near the transcription start site (TSS), a property possibly related to its role in RNA degradation. Finally, we found that groups of APA events regulated by C/P factors are also modulated in cell differentiation and development with distinct trends. Together, our results support an APA code where an APA event in a given cellular context is regulated by a number of parameters, including relative location to the TSS, splicing context, distance between competing pAs, surrounding cis elements and concentrations of core C/P factors.

Huntington’s disease (HD) is a hereditary neurodegenerative disorder caused by expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats in the huntingtin ( HTT ) gene. Consequently, the mutant protein is ubiquitously expressed and drives pathogenesis of HD through a toxic gain-of-function mechanism. Animal models of HD have demonstrated that reducing huntingtin (HTT) protein levels alleviates motor and neuropathological abnormalities. Investigational drugs aim to reduce HTT levels by repressing HTT transcription, stability or translation. These drugs require invasive procedures to reach the central nervous system (CNS) and do not achieve broad CNS distribution. Here, we describe the identification of orally bioavailable small molecules with broad distribution throughout the CNS, which lower HTT expression consistently throughout the CNS and periphery through selective modulation of pre-messenger RNA splicing. These compounds act by promoting the inclusion of a pseudoexon containing a premature termination codon (stop-codon psiExon), leading to HTT mRNA degradation and reduction of HTT levels. Here the authors describe the discovery of a class of small molecule splicing modifiers which are orally bioavailable, cross the blood-brain barrier, and lower levels of huntingtin in a mouse model of Huntington’s disease (HD).

To improve the overall mechanization level of rapeseed production in China, especially in some hilly regions where ground machinery cannot enter the fields or can only enter with very low economic benefits, a special aerial seeding system for rapeseed based on a miniature air-assisted centralized metering device was designed and tested in this study. Unlike existing commercial aerial seeding systems, the proposed seed meter was a miniaturized version derived from the traditional air-feeding seed meter on ground planters. The new version contained a redesigned seed feeding component to overcome problems of serious air backflow to the seed box and difficult seed feeding after miniaturization. Three groups of experiments were designed and conducted to optimize the parameters of the seed meter and test its performance. Results from the orthogonal experiment showed that the seed feeding component performed best when the seed layer thickness was 45 mm, the rotational speed of the gear disc was 45 r/min, and the airflow pressure was 2450 Pa. Results from the static workbench test showed that the designed seeding system had a maximum average total sowing efficiency of 537.17 g/min, with the maximum values of the stability variation coefficient of total seeding rate (seven ports) and the consistency variation coefficient between each port was 2.37% and 4.89%, respectively. Field tests further proved that the designed aerial seeding system could work stably, uniformly, and efficiently, so that the agronomic requirements of rape crop planting could be well met.

The dynamical behavior of a Duffing oscillator under periodic excitation is investigated using semi-analytical methods. Bifurcation trees with varying periodic excitation are constructed. The stability, saddle-node bifurcation and period-doubling bifurcation are revealed by assessing the eigenvalue of the model. From the bifurcation trees, we observed that saddle-node and period-doubling bifurcations occur when the excitation frequency and excitation amplitude vary to an appropriate value. The generation of periodic-doubling bifurcation leads to a change in the periodicity of periodic motion. The relationships among periodic-m motions are interconnected yet independent of each other. To satisfy the need of parameter selection for FPGA circuits, a dual-parameter map is calculated to study the periodic characteristics. Then, an FPGA circuit model is designed and implemented. The results show that the phase trajectory and waveform of the FPGA hardware circuit match the numerical model.

Multi-core fiber (MCF) is expected to be a good candidate to overcome the capacity limit of single-mode single-core fiber. However, only linear inter-crosstalk was considered in the performance of MCF. In this study, the performance of the transmission channel in terms of the signal-to-noise ratio (SNR) in weakly coupled MCF transmission systems is investigated by taking into account the effect of intra-core nonlinear interference noise (NLIN) and nonlinear inter-core crosstalk (NICXT). The SNR is calculated with various MCF system parameters to assess corresponding transmission performance. The results show that the SNR cannot always be improved by increasing the transmitted power in both the SCF and MCF systems. NICXT can deteriorate the performance of the MCF system, obviously, especially when the transmitted power is smaller than the threshold power. Furthermore, this influence is more marked with a small coupling coefficient.

The PAF complex (Paf1C) has been shown to regulate chromatin modifications, gene transcription, and RNA polymerase II (PolII) elongation. Here, we provide the first genome-wide profiles for the distribution of the entire complex in mammalian cells using chromatin immunoprecipitation and high throughput sequencing. We show that Paf1C is recruited not only to promoters and gene bodies, but also to regions downstream of cleavage/polyadenylation (pA) sites at 3' ends, a profile that sharply contrasted with the yeast complex. Remarkably, we identified novel, subunit-specific links between Paf1C and regulation of alternative cleavage and polyadenylation (APA) and upstream antisense transcription using RNAi coupled with deep sequencing of the 3' ends of transcripts. Moreover, we found that depletion of Paf1C subunits resulted in the accumulation of PolII over gene bodies, which coincided with APA. Depletion of specific Paf1C subunits led to global loss of histone H2B ubiquitylation, although there was little impact of Paf1C depletion on other histone modifications, including tri-methylation of histone H3 on lysines 4 and 36 (H3K4me3 and H3K36me3), previously associated with this complex. Our results provide surprising differences with yeast, while unifying observations that link Paf1C with PolII elongation and RNA processing, and indicate that Paf1C subunits could play roles in controlling transcript length through suppression of PolII accumulation at transcription start site (TSS)-proximal pA sites and regulating pA site choice in 3'UTRs.